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The role of the VEGF signaling pathway in angiogenesis has been extensively investigated, and many new targeted anti-angiogenic drugs have evolved from this knowledge. The recent approval and introduction of these anti-neoplastic drugs has revolutionized the treatment of many types of cancers, but has also revealed numerous toxicities to the skin and its adnexae. Since these cutaneous side effects may have a significant impact on the physical, emotional and psychosocial health of patients, it is important for dermatologists and oncologists alike to be aware of the cutaneous complications of these drugs in order to properly diagnose and treat them. This review will detail the presentation of the cutaneous complications of the anti-angiogenic drugs, most notably bevacizumab, sorafenib and sunitinib, and shed light on the management of such adverse reactions." | Receptors, Vascular Endothelial Growth Factor |
To evaluate the interactions among endophytes, plants and heavy metal/arsenic contamination, root endophytic bacteria of Prosopis laevigata (Humb and Bonpl. ex Willd) and Sphaeralcea angustifolia grown in a heavy metal(loid)-contaminated zone in San Luis Potosi, Mexico, were isolated and characterized. Greater abundance and species richness were found in Prosopis than in Sphaeralcea and in the nutrient Pb-Zn-rich hill than in the poor nutrient and As-Cu-rich mine tailing. The 25 species identified among the 60 isolates formed three groups in the correspondence analysis, relating to Prosopis/hill (11 species), Prosopis/mine tailing (4 species) and Sphaeralcea/hill (4 species), with six species ungrouped. Most of the isolates showed high or extremely high resistance to arsenic, such as >/=100 mM for As(V) and >/=20 mM for As(III), in mineral medium. These results demonstrated that the abundance and community composition of root endophytic bacteria were strongly affected by the concentration and type of the heavy metals and metalloids (arsenic), as well as the plant species. | Prosopis |
Glycine N-methyltransferase, an enzyme that uses S-adenosylmethionine to methylate glycine with the production of sarcosine, was recently shown to be identical with a major folate binding protein of rat liver (Cook, R.J. and Wagner, C. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 3631-3634). We now present evidence that 5-methyltetrahydropteroylpentaglutamate (5-CH3-H4PteGlu5) is bound with high specificity, and is a powerful inhibitor of the enzyme. It is proposed that this information may be used to modify the methyl trap" hypothesis which describes how the availability of one-carbon units is regulated by folate, vitamin B12 and methionine." | Pteroylpolyglutamic Acids |
In four of the five autosomal dominant porphyrias four different partial enzymatic defects of the porphyrin biosynthetic pathway have been discovered in the last few years. With the exception of protoporphyria, the residual enzymatic activity in carriers of these defects is approximately equal to 50% of that found in controls. In each case the pattern of excretion of porphyrin and/or porphyrin precursors reflects the stie of the partial metabolic block. There are indications, at least in intermittent acute porphyria, that the degree of penetrance of the disorder varies according to the level of phenotypic expression, being highest for the enzyme deficiency, lower for the excretion of precursors and lowest for the clinical symptoms. It is proposed that environmental factors, and probably also gene interaction, are the cause of the different degrees of penetrance. | Coproporphyrins |
Chronobiology is the study of biological rhythms. Chronomics investigates interactions with environmental cycles in a genetically coded autoresonance of the biosphere with wrangling space and terrestrial weather. Analytical global and local methods applied to human blood pressure records of around-the-clock measurements covering decades detect physiological-physical interactions, a small yet measurable response to solar and terrestrial magnetism. The chronobiological and chronomic interpretation of ambulatory blood pressure monitoring (C-ABPM) records in the light of time-specified reference values derived from healthy peers matched by sex and age identify vascular variability anomalies (VVAs) for an assessment of cardio-, cerebro-, and renovascular disease risk. Even within the conventionally accepted normal range, VVAs have been associated with a statistically significant increase in risk. Long-term C-ABPM records help to know ourselves," serving for relief of psychological and other strain once transient VVAs are linked to the source of a load, prompting adjustment of one's lifestyle for strain reduction. Persistent circadian VVAs can be treated, sometimes by no more than a change in timing of the daily administration of antihypertensive medication. Circadian VVA assessment is an emergency worldwide, prompted in the United States by 1,000 deaths per day every day from problems related to blood pressure. While some heads of state met under United Nation and World Health Organization sponsorship to declare that noncommunicable diseases are a slow-motion disaster, a resolution has been drafted to propose C-ABPM as an added tool complementing purely physical environmental monitoring to contribute also to the understanding of social and natural as well as personal cataclysms." | Drug Chronotherapy |
This work investigated the mechanisms induced by exercise training that may contribute to attenuate dexamethasone (DEX)-induced microvascular rarefaction and hypertension. Wistar rats underwent training protocol or were kept sedentary for 8 weeks. Dexamethasone was administered during the following 14-days and hemodynamic parameters were recorded at the end. Capillary density (CD) and capillary-to-fiber ratio (C:F ratio) were obtained in soleus muscle (SOL). Also, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2), endothelial nitric oxide synthase (eNOS), B-cell lymphoma 2 (Bcl-2), Bcl-2-like protein 4 (Bax), p-BAX and caspase-3 cleaved protein levels were analyzed. DEX treatment significantly increased blood pressure (+14%), which was associated with reduced C:F ratio (-41.0%) and CD (-43.1%). Reduction of vessel density was associated with decreased VEGF (-15.6%), VEGFR-2 (-14.6%), Bcl-2 (-18.4%), Bcl-2/Bax ratio (-29.0%) and p-Bax/Bax (-25.4%), and also with increased caspase-3 cleaved protein level (25%). Training, on the other hand, prevented microvessels loss by mitigating all proteins changes induced by DEX. In addition, angiogenic and apoptotic proteins were significantly correlated with CD, which, in turn, was associated with blood pressure. Therefore, we may point out that exercise training is a good strategy to attenuate DEX-induced microvascular rarefaction in soleus muscle and this response involves a better balance between apoptotic and angiogenic proteins, which may contribute for the attenuation of hypertension. | Microvascular Rarefaction |
Black-fronted titi monkeys, Callicebus nigrifrons, are endemic primates of the Atlantic forest of Brazil, and little is known about their diet and how it is affected by seasonal changes. The aim of this study is to analyze the diet of C. nigrifrons during a bamboo masting year. This study was conducted in the reserve RPPN Santuario do Caraca, MG, and the collection of data was carried out from January 2007 to January 2008 through monthly campaigns. The feeding behaviour of four habituated groups in the same forest fragment was observed. The data were collected through focal animal observations of 10 min each with instantaneous recording of behaviour every 30 s, totalling 220.5 h of observations during 71 field days. The diet of groups consisted of 43.4% fruit, 37.0% seeds, 8.2% leaves, 6.2% flowers, 2.5% animal matter and 2.7% non-identified/other items. At least 51 species of plants were consumed. More than half of the diet comprised only five species: Merostachys fischeriana (bamboo, 32.3%), Solanum cinnamomum (nightshade, 8.7%), Vitex spp. (Lamiaceae, 4.5%), Casearia decandra (wild honeytree, 3.8%) and Amaioua guianensis (woody dioecious species, 3.7%). According to the values obtained from Levins' index analysis (0.05-0.28) our subjects had a narrow diet width. The individuals in this study were able to incorporate significant amounts of bamboo seeds in their diet, and this was inversely related to fruit consumption. In conclusion, C. nigrifrons was able to amply exploit a bamboo masting event, which generated a narrow diet width. | Pitheciidae |
With the widespread use of postmortem computed tomography (PMCT) beside forensic autopsies for investigation of causes of death, three-dimensional (3D) reconstruction and fusion imaging using PMCT data are now becoming common. In the present study, the applicability of virtual reassembly from PMCT data was investigated in three cases involving fragmentation of the skull or spine due to high-energy trauma, as in such cases it is sometimes difficult to obtain detailed information on fractures using macroscopic observation alone. In the first case, virtual reassembly of the skull provided more information about the fractures than conventional reconstruction with adhesive. In the second case, although the skull was severely fractured and could not be examined macroscopically, virtual reassembly allowed detailed visualization of the fractures. In the last case, virtual reassembly of the spine helped to clarify that the 6th-8th thoracic vertebrae had been run over by a vehicle at the scene. Thus, virtual reassembly was shown to be useful for assessment of injury patterns, and event reconstruction. | Forensic Pathology |
Health sector reform is 'a sustained process of fundamental changes in national health policy, institutional arrangements, etc. guided by government and designed to improve the functioning and performance of the health sector and, ultimately, the health status of the population'. All the forty six countries in the African Region of the World Health Organisation have embarked on one form of health sector reform or the other. The contexts and contents of their health reform programmes have varied from one country to another. Health reforms in the region have been influenced largely by the poor performance of the health systems, particularly with regard to the quality of health services. Most countries have taken due congnizance of the deficiencies on their health systems in the design of their health reform programmes and they have made some progress in the implementation of such programmes. Indeed, some countries have adopted sector-wide approaches (SWAps) in developing and implementing their health reform programmes. Since countries are at various stages of implementing their health reform programmes, there is a lot of potential for countries to learn from one another. This paper is a synthesis of the experiences of the countries of the Region in the development and implementation of their health sector reform programmes. It also highlights the future perspectives in this important area. | Health Policy |
In this study, comprehensive characterization and drying methods on properties of bacterial cellulose were analyzed. Bacterial cellulose was prepared by Gluconacetobacter hansenii CGMCC 3917, which was mutated by high hydrostatic pressure (HHP) treatment. Bacterial cellulose is mainly comprised of cellulose Ialpha with high crystallinity and purity. High-water holding and absorption capacity were examined by reticulated structure. Thermogravimetric analysis showed high thermal stability. High tensile strength and Young's modulus indicated its mechanical properties. The rheological analysis showed that bacterial cellulose had good consistency and viscosity. These results indicated that bacterial cellulose is a potential food additive and also could be used for a food packaging material. The high textural stability during freeze-thaw cycles makes bacterial cellulose an effective additive for frozen food products. In addition, the properties of bacterial cellulose can be affected by drying methods. Our results suggest that the bacterial cellulose produced from HHP-mutant strain has an effective characterization, which can be used for a wide range of applications in food industry. | Gluconacetobacter |
Arthropods have long been utilized as models to explore molecular function, and the findings derived from them can be applied throughout metazoa, including as a basis for medical research. This has led to the adoption of many representative insect models beyond Drosophila, as each lends its own unique perspective to questions in endocrinology and genetics. However, non-insect arthropods are yet to be realised for the potential insight they may provide in such studies. The Crustacea are among the most ancient arthropods from which insects descended, comprising a huge variety of life histories and ecological roles. Of the events in a typical crustacean development, metamorphosis is perhaps the most ubiquitous, challenging and highly studied. Despite this, our knowledge of the endocrinology which underpins metamorphosis is rudimentary at best; although several key molecules have been identified and studied in depth, the link between them is quite nebulous and leans heavily on well-explored insect models, which diverged from the Pancrustacea over 450 million years ago. As omics technologies become increasingly accessible, they bring the prospect of explorative molecular research which will allow us to uncover components and pathways unique to crustaceans. This review reconciles known components of crustacean metamorphosis and reflects on our findings in insects to outline a future search space, with focus given to the ecdysone cascade. To expand our knowledge of this ubiquitous endocrine system not only aids in our understanding of crustacean metamorphosis, but also provides a deeper insight into the adaptive capacity of arthropods throughout evolution. | Ecdysone |
INTRODUCTION: Coronavirus disease COVID-19 rapid antigen tests are a useful tool in detecting infection, and their use has increased in many countries since they became commercially available in late 2021. Some rapid antigen tests contain sodium azide, which can be toxic in small doses. This study aimed to describe the clinical characteristics of exposures to COVID-19 rapid antigen tests. METHODS: This is a prospective study conducted by the New South Wales Poisons Information Centre. From 22 January 2022 to 31 August 2022, rapid antigen test exposures were followed up to obtain outcome information. Data collected included: brand/ingredients, exposure route, demographics, symptoms, and disposition. RESULTS: We recorded 218 exposures in the seven-month study period. Complete follow-up information was available in 75% (n = 164). There were 53 exposures to sodium azide-containing products (35 with follow-up data) and 165 to non-sodium azide-containing products and unknown ingredient exposures (129 with follow-up data). Overall, unintentional exposures predominated (n = 182), and 151 were ingestions. The vast majority (>90%) did not develop symptoms, and all symptoms that developed were mild. Most cases (95%, n = 208) did not require referral to a healthcare facility. CONCLUSIONS: In this prospective series, few patients developed symptoms, regardless of the sodium azide content, likely due to low concentration and low volume within the test kits. However, ongoing toxicovigilance is warranted. | Sodium Azide |
This study aimed to evaluate a system that identifies cartilage turn over and/or degradation through measurement of a new keratan sulfate (KS) epitope concentration in equine sera. Blood samples were collected from 30 horses, 1 (n = 15) and 2 year-olds (n = 15). Serum samples were analyzed for an epitope of keratan sulfate by 1/20/5D4 (KS5D4) and new epitopes of keratan sulfate using high sensitive keratan sulfate (HSKS), measured by two respective enzyme-linked immunosorbant assays (ELISAs). There was no correlation in serum concentration of KS evaluated using 5D4 and HSKS. Age had no significant effect on concentrations of KS measured with KS5D4 while 1 year-old horses showed significantly higher amounts than 2 year-olds with HSKS. Results suggest that HSKS could detect early signs of cartilage metabolic changes." | Enzyme-Linked Immunosorbent Assay |
Vitreoretinal lymphomas are rare ocular cancers, and the subset of primary central nervous system lymphomas that are based in the posterior eye. These tumours are challenging to treat, and today management generally involves a multispecialty team coordinating a treatment protocol that may include intraocular chemotherapy, ocular irradiation, systemic chemotherapy and/or autologous stem cell transplantation. The ophthalmologist has specific responsibility for the intraocular chemotherapy, which is delivered to the eye by intravitreal injection. The most commonly injected drugs are methotrexate-an anti-metabolite-and rituximab-an anti-human B cell monoclonal antibody. A range of intraocular chemotherapy treatment schedules have been described in the medical literature, although to date there have been no randomized clinical trials of these schedules. In this article, we review the development and current status of intraocular chemotherapy for vitreoretinal lymphoma. | Intraocular Lymphoma |
One of the biggest ambitions in the field of anorexia nervosa (AN) research is to find a reliable and effective pharmacological treatment. The fact that currently no pharmacological treatment is safe and effective in this disease is worrying and also challenging. On the basis of the progress in our understanding of AN neurobiology, we propose that escitalopram, a widely available drug, might be a safe and effective option that needs to be investigated. Escitalopram is the only selective serotonin reuptake inhibitor, without any catecholaminergic effect. As studies have shown decreased serotonergic and increased dopaminergic transmission in AN, we hypothesized that an ideal drug for AN management should boost serotonin levels to increase serotonergic and decrease dopaminergic transmission, the two main features of escitalopram action. Here, we present a short overview of pharmacological research in AN and discuss the theoretical rationale for escitalopram use in AN. We also call for double-blind, randomized, placebo-controlled trials to test whether this theoretical framework translates into clinical efficacy. | Escitalopram |
Basic concepts of 'dose/concentration additivity' and 'response addition/independence' may be applied to evaluate chemical mixtures in human toxicology, as well as in ecotoxicology. In the case of compounds that cause the same toxicological effect by the same mechanism, 'dose addition' is a more plausible form of joint action than 'response addition'. Data on the effects of halogenated hydrocarbons on the kidney, the effects of organic solvents on the central nervous system, and the effects of organophosphates on cholinesterase, are the basis of this assumption. For such compounds, response addition will generally underestimate risk. None the less, both dose addition and response addition are 'non-interactive' forms of joint action. As such, neither additivity assumption will accurately predict risk for compounds that exhibit toxicological interactions regardless of the primary mechanism(s) of toxicity. More often, the additivity approach overestimates the risk of a combination of chemicals. From a public health perspective, such results over-protect the public; hence this approach can be used for standard setting. The introduction of a special safety factor of 10 for the standard setting for mixtures in addition to those normally used for deriving acceptable daily intakes, reference doses or minimal risk levels is not supported by data. Instead, each exposure scenario should be considered on a case-by-case basis. Furthermore, considerations of multiple endpoints, including multiple organs, multiple effects, multiple mechanisms and potential interactions between such mechanisms, are very desirable for overall toxicity and risk assessment of chemical mixtures. In conclusion, additivity could be used to estimate potential risks for a combination of chemicals: only if scientific data support independence of effects can response independence be used as an alternative for standard setting. | Pharmacological Phenomena |
Prerenal failure is used to designate a reversible form of acute renal dysfunction. However, the terminology encompasses different conditions that vary considerably. The Acute Kidney Injury Network group has recently standardized the acute kidney injury (AKI) definition and classification system; however, these criteria have not determined specific diagnostic criteria to classify prerenal conditions. The difference in the pathophysiology and manifestations of prerenal failure suggests that our current approach needs to be revaluated. Several mechanisms are recognized as contributory to development of a prerenal state associated with cardiac failure. Because of the broad differences in patients' reserve capacity and functional status, prerenal states may be triggered at different time points during the course of the disease. Prerenal state needs to be classified depending on the underlying capacity for compensation, the nature, timing of the insult and the adaptation to chronic comorbidities. Current diagnosis of prerenal conditions is relatively insensitive and would benefit from additional research to define and classify the condition. Identification of high-risk states and high-risk processes associated with the use of new biomarkers for AKI will provide new tools to distinguish between the prerenal and established AKI. Achieving a consensus definition for prerenal syndrome will allow physicians to describe treatments and interventions as well as conduct and compare epidemiological studies in order to better describe the implications of this syndrome. | Azotemia |
Human bleomycin hydrolase (hBH) catalyzes deamidation of the anticancer drug bleomycins (BLM). This enzyme is involved in BLM detoxification and drug resistance. Herein, we report the putative BLM-binding site and catalytic mechanism of hBH. The crystal structures and biochemical studies suggest that hBH cleaves its C-terminal residue without significant preference for the type of amino acid, and therefore can accordingly accommodate the beta-aminoalanine amide moiety of BLM for deamidation. Interestingly, hBH is capable of switching from a cysteine protease to a serine protease that is unable to cleave the secondary amide of hBH C-terminus but reacts with the primary amide of BLMs. | Bleomycin |
SR and hnRNP proteins were initially discovered as regulators of alternative splicing: the process of controlled removal of introns and selective joining of exons through which multiple transcripts and, subsequently, proteins can be expressed from a single gene. Alternative splicing affects genes involved in all crucial cellular processes, including apoptosis. During cancerogenesis impaired apoptotic control facilitates survival of cells bearing molecular aberrations, contributing to their unrestricted proliferation and chemoresistance. Apparently, SR and hnRNP proteins regulate all levels of expression of apoptotic genes, including transcription initiation and elongation, alternative splicing, mRNA stability, translation, and protein degradation. The frequently disturbed expressions of SR/hnRNP proteins in cancers lead to impaired functioning of target apoptotic genes, including regulators of the extrinsic (Fas, caspase-8, caspase-2, c-FLIP) and the intrinsic pathway (Apaf-1, caspase-9, ICAD), genes encoding Bcl-2 proteins, IAPs, and p53 tumor suppressor. Prototypical members of SR/hnRNP families, SRSF1 and hnRNP A1, promote synthesis of anti-apoptotic splice variants of Bcl-x and Mcl-1, which results in attenuation of programmed cell death in breast cancer and chronic myeloid leukemia. SR/hnRNP proteins significantly affect responses to chemotherapy, acting as mediators or modulators of drug-induced apoptosis. Aberrant expression of SRSF1 and hnRNP K can interfere with tumor responses to chemotherapy in pancreatic and liver cancers. Currently, a number of splicing factor inhibitors is being tested in pre-clinical and clinical trials. In this review we discuss recent findings on the role of SR and hnRNP proteins in apoptotic control in cancer cells as well as their significance in anticancer treatments." | Heterogeneous-Nuclear Ribonucleoproteins |
Because of the pandemic's impact on morbidity and mortality, nursing leaders have witnessed a marked increase in the number of staff who experience crisis and extreme stress during their shift. This hospital's Engagement and Resilience Council aimed to mediate this stress by implementing resilience-building interventions during moments of peaked stress. Preliminary data show these interventions may markedly improve stress levels in frontline caregivers by up to 52% in some clinical settings. | Shared Governance, Nursing |
INTRODUCTION: Dupuytren's disease (DD) is a proliferative fibromatosis of the hand, which causes permanent flexion contracture of the digits and, ultimately, loss of function. The treatment of DD is complex and involves surgical and nonsurgical approaches, with the goal of removing the affected tissue. New biological targets are under investigation in order to develop innovative therapies. AREAS COVERED: The etiology of DD is still unknown. Several authors who focused their studies on the genetics of DD recognized an inherited autosomal dominant pattern. Actually, DD is a multifactorial and complex disease. Myofibroblasts are thought to play a crucial role in its pathogenesis, although their origin is not clear. EXPERT OPINION: There is a general consensus that a better understanding of cellular and molecular mechanisms of DD will lead to the design of more specific and effective treatment alternatives. In this review, the authors hypothesize a new biological model for DD pathology, where myofibroblasts enhance the reservoir of the disease acting as if in a vicious cycle. This could help, ultimately, in identifying new therapeutic strategies to treat this common and disabling fibroproliferative disorder. | Dupuytren Contracture |
Allele-specific expression analysis of hybrid mice provides new insights into the genetic substrates of behavioral evolution. As a complement to QTL mapping, this approach, described by Hu et al. in this issue of Cell Reports, holds promise for identifying causative regulatory loci that influence species-specific behavior. | Peromyscus |
Edible oil adulteration is a main concern for consumers. This paper presents a study on the use of smartphone, coupled with image processing and chemometrics, to quantify adulterant levels in extra virgin olive oil. A sequence of light with varying colours is generated on the phone screen, which is used to illuminate oil samples. Videos are recorded to capture the colour changes on sample surface and are subsequently converted into spectral data for analysis. To evaluate the performance of this video approach, partial least squares regression models constructed from such video data as well as near-infrared, ultraviolet-visible and digital imaging data are compared in the task of quantifying the level of vegetable oil in extra virgin olive oil in the range 5%-50% (v/v). The results show that the video approach (R(2) = 0.98 and RMSE = 0.02) yields comparable performance to baseline spectroscopy techniques and outperforms computer vision system approach. Since the smartphone-based sensor system is low-cost and easy to operate, it has high potential to become a consumer-oriented solution for detecting edible oil adulteration. | Olive Oil |
Sectional imaging by CT and MRI now displays the gross anatomy of the orbit in vivo. Gross anatomy, axial and coronal CT, and MRI will be used to review the anatomic features of the orbit critical to image interpretation. Familiarity with the positions, relationships, and normal appearance of the major structures described and illustrated in this article will provide a solid basis for interpreting images of orbital pathology, as discussed in subsequent articles. | Orbit |
BACKGROUND: Eimeria is a common genus of apicomplexan parasites that infect diverse vertebrates, most notably poultry, causing serious disease and economic losses. Eimeria species have complex life-cycles consisting of three developmental stages. However, the molecular basis of the Eimeria reproductive mode switch remains an enigma. METHODS: Total RNA extracted from second- (MZ-2) and third-generation merozoites (MZ-3) of Eimeria necatrix was subjected to transcriptome analysis using RNA sequencing (RNA-seq) followed by qRT-PCR validation. RESULTS: A total of 6977 and 6901 unigenes were obtained from MZ-2 and MZ-3, respectively. Approximately 2053 genes were differentially expressed genes (DEGs) between MZ-2 and MZ-3. Compared with MZ-2, 837 genes were upregulated and 1216 genes were downregulated in MZ-3. Approximately 95 genes in MZ-2 and 48 genes in MZ-3 were further identified to have stage-specific expression. Gene ontology category and KEGG analysis suggested that 216 upregulated genes in MZ-2 were annotated by 70 GO assignments, 242 upregulated genes were associated with 188 signal pathways, while 321 upregulated genes in MZ-3 were annotated by 56 GO assignments, 322 upregulated genes were associated with 168 signal pathways. The molecular functions of upregulated genes in MZ-2 were mainly enriched for protein degradation and amino acid metabolism. The molecular functions of upregulated genes in MZ-3 were mainly enriched for transcriptional activity, cell proliferation and cell differentiation. CONCLUSIONS: To the best of our knowledge, this is the first RNA-seq data study of the MZ-2 and MZ-3 stages of E. necatrix; it demonstrates a high number of differentially expressed genes between the MZ-2 and MZ-3 of E. necatrix. This study forms a basis for deciphering the molecular mechanisms underlying the shift from the second to third generation schizogony in Eimeria. It also provides valuable resources for future studies on Eimeria, and provides insight into the understanding of reproductive mode plasticity in different Eimeria species. | Merozoites |
This study investigated the organising principles of touch. We examined specialisations within the haptic system and their hemispheric distribution. Haptic processing consists of the integration of data from multiple sources to form a single percept. Previous research provides strong support for a hierarchical and functional distribution within haptic processing. We investigated hemispheric asymmetry in haptic discrimination of objects with differing textures and centres of mass. By analogy with vision it was hypothesised that participants would demonstrate a left-hand advantage for centre of mass discrimination (a 'global', presumed right hemisphere, judgement) and a right-hand advantage for surface texture judgements (a 'local', presumed left hemisphere discrimination). We found that left-handed participants showed these effects to a lesser degree than did the right-handers, consistent with the notion that left-handed people generally show weaker asymmetries in bimanual tasks. In a second experiment the effect of conflicting information on haptic percept formation was investigated. Following from the previous hypotheses it was predicted that participants would be more accurate with their right hands at judging conflicting surfaces. Contrary to predictions an advantage was demonstrated for the left hand for texture discrimination and for the right hand for centre of mass judgement. | Stereognosis |
Due to its capability to self-assemble in self-supporting hydrogels (HG) under physiological conditions, Fmoc-FF is one of the most studied ultra-short peptide. The structural properties of the resulting hydrogel (mechanical rigidity, entanglement of the fibrillary network, and the thickness of the fibers) strictly depend on the experimental conditions used during the preparation. In the past few years, a broad range of applications in different fields, such as biomedical and industrial fields, have been proposed. However, the research on novel materials with enhanced mechanical properties, stability, and biocompatibility has brought about the development of novel Fmoc-FF-based hybrid systems, in which the ultra-short hydrogelator is combined with others entities such as polysaccharides, polymers, peptides, or organic molecules. The structural features and the potential applications of these novel hybrid materials, with particular attention to tissue engineering, drug delivery, and catalysis, are described here. The aim is to give the readers a tool to design new hybrid nanomaterials based on the Fmoc-FF dipeptide hydrogelator, with appropriate properties for specific applications. | Phenylalanine |
OBJECTIVE: To determine whether there is an increase in use of antiparkinsonian therapy in older persons taking metoclopramide hydrochloride. DESIGN: Case-control study. SETTING: New jersey Medicaid program. PATIENTS: Medicaid enrollees aged 65 years and older. Cases were patients newly prescribed a levodopa-containing medication (n = 1253); a secondary case group were patients newly prescribed an anticholinergic antiparkinsonian drug (n = 2377). The control group consisted of 16435 Medicaid enrollees older than 65 years who were not users of any antiparkinsonian therapy. MAIN OUTCOME MEASURES: We used logistic regression to determine the odds ratio (OR) for the initiation of antiparkinsonian therapy in patients using metoclopramide relative to nonusers, after adjusting for age, sex, race, nursing home residence, exposure to antipsychotic medication, and days hospitalized. RESULTS: Metoclopramide users were three times more likely to begin use of a levodopa-containing medication compared with nonusers (OR = 3.09; 95% confidence interval [Cl], 2.25 to 4.26). Risk increased with increasing daily metoclopramide dose: the OR was 1.19 (95% Cl, 0.50 to 2.81) for more than 0 to 10 mg per day, 3.33 (95% Cl, 1.98 to 5.58) for more than 10 to 20 mg per day, and 5.25 (95% Cl, 1.16 to 8.50) for more than 20mg per day. The effect persisted after adjustment for demographic, health service utilization, and medication use variables. The OR for initiation of anticholinergic antiparkinsonian drugs was also elevated in metoclopramide users. CONCLUSION: Metoclopramide use confers an increased risk for the initiation of treatment generally reserved for the management of idiopathic Parkinson's disease in patients with drug-induced parkinsonian symptoms, which should be ruled out before starting dopaminergic therapy for this condition. | Metoclopramide |
This study describes the possibility of active and passive immunization for tetrodotoxin (TTX) poisoning. TTX was conjugated to keyhole limpet hemocyanin and this conjugate was used as an immunogen in rabbits and mice. Mice immunized with the conjugate were protected from a lethal dose of TTX. Passive protection experiments demonstrated that immunoglobulin from rabbit antiserum exhibited a dose-related therapeutic activity in mice after challenge with TTX. | Tetrodotoxin |
Inner ear disorders such as sensorineural deafness and genetic diseases may one day be treated with local drug delivery to the inner ear. Current pharmacokinetic models have been based on invasive methods to measure drug concentrations, limiting them in spatial resolution, and restricting the research to larger rodents. We developed an intracochlear pharmacokinetic model based on an imaging, learning-prediction (LP) paradigm for learning transport parameters in the murine cochlea. This was achieved using noninvasive micro-computed tomography imaging of the cochlea during in vivo infusion of a contrast agent at the basal end of scala tympani through a cochleostomy. Each scan was registered in 3-D to a cochlear atlas to segment the cochlear regions with high accuracy, enabling concentrations to be extracted along the length of each scala. These spatio-temporal concentration profiles were used to learn a concentration dependent diffusion coefficient, and transport parameters between the major scalae and to clearance. The LP model results are comparable to the current state of the art model, and can simulate concentrations for cases involving different infusion molecules and different drug delivery protocols. Forward simulation results with pulsatile delivery suggest the pharmacokinetic model can be used to optimize drug delivery protocols to reduce total drug delivered and the potential for toxic side effects. While developed in the challenging murine cochlea, the processes are scalable to larger animals and different drug infusion paradigms. | Iopamidol |
Case histories of 47 patients with histologically confirmed carcinoma of extrahepatic bile ducts presenting to M. D. Anderson Hospital and Tumor Institute over a 30-year period were studied. The disease was more common in males during the sixth and seventh decades of life. A third of the patients had history of cholelithiasis. Four patients had prior history of chronic ulcerative colitis and one patient had congenital choledochal cyst prior to development of cancer of the bile duct. Jaundice was the earliest and the most common presenting sign. The tumor was located in the common bile duct more often than in the hepatic ducts. The overall median survival was eight months with two-year and five-year survival rates of 15% and 3%, respectively. The respective values for patients who had resectable tumors were 21.7 months, 57% and 20%. Ascending cholangitis was a frequent complication in patients treated with dilation and intubation and, overall, hepatic failure and systemic infection were more frequent causes of death than distant metastases. | Adenoma, Bile Duct |
Historical prospectives of hypertension studies are introduced. The pathophysiology of hypertension, renin-angiotensin-aldosterone system, urea-angiotensin interactions, and essential hypertension are reviewed. The causes of secondary hypertension, especially the renovascular and endocrine causes in the child, neonate and post-transplant patients are discussed. Comments are made on the medical costs of diagnostic work-up. Treatment for hypertension is summarized. | Hypertension, Renal |
Existence of a receptor protein for acetylcholine has been postulated, and the hypothesis has been supported by experiments in intact cells. A protein from electric tissue has now been obtained in solution; there is striking parallelism between the ability of this protein to bind acetylcholine analogs and the effects of such analogs on electrical manifestations of intact electroplax. | Curare |
1. We have used the whole-cell patch clamp technique to study the effect of the partial anti-oestrogens clomiphene and nafoxidine, the pure anti-oestrogens ICI 182,780 and RU 58,668 and the oestrogen ss-estradiol, on the volume-regulated anion channel (VRAC) in cultured pulmonary artery endothelial (CPAE) cells. 2. In contrast to the pure anti-oestrogens and ss-estradiol, clomiphene and nafoxidine potently inhibited the volume-sensitive chloride current, I(Cl,swell), activated by challenging CPAE cells with a 25% hypotonic solution. For clomiphene, the estimated IC(50) and Hill coefficient were 1.03+/-0.14 microM and 1.40+/-0.21 respectively. In the case of nafoxidine, these values were 1.61+/-0.29 microM and 1.24+/-0.19. 3. The inhibition induced by the pure enantiomers of clomiphene, zuclomiphene and enclomiphene, was not different from that of the racemic mixture, indicating that the interaction between clomiphene and VRAC is not stereoselective. 4. Clomiphene and nafoxidine inhibited proliferation of CPAE cells. Half-maximal inhibition was found at 1.98+/-0.17 and 1.66+/-0.21 microM respectively, concentrations similar to those for half-maximal block of VRAC. 5. In conclusion, the nonsteroidal partial anti-oestrogens nafoxidine and clomiphene are potent inhibitors of volume-regulated anion channels. The inhibition by clomiphene is not stereoselective and occurs at concentrations close to therapeutically relevant concentrations. Finally, both drugs inhibit the proliferation of endothelial cells. | Nafoxidine |
Helix A and -C of alpha-lactalbumin, a loosely folded amphitropic protein, perturb lipid monolayers by the formation of amyloid pore-like structures. To investigate whether these helices are able to disrupt fully formed bilayers, we designed peptides comprised of Helix A and -C, and investigated their membrane-perturbing properties. The peptides, designated A-Cage-C and A-Lnk-C, were prepared with tryptophan sites in the helical and the spacer segments in order to monitor which part were involved in membrane association under given conditions. The peptides associate with and disrupt negatively charged bilayers in a pH-dependent manner and alpha-helical tendencies increased upon membrane association. Both helices and the spacer segment were involved in membrane binding in the case of A-Lnk-C, and there are indications that the two helixes act in synergy to affect the membrane. However, the helices and the spacer segment could not intercalate when present as A-Cage-C at neutral conditions. At acidic pH, both helices could intercalate, but not the central spacer segment. AFM performed on bilayers under aqueous conditions revealed oligomers formed by the peptides. The presence of bilayers and acidic pHs were both drivers for the formation of these, suggestive of models for peptide oligomerization where segments of the peptide are stacked in an electrostatically favorable manner by the surface. Of the two peptides, A-Lnk-C was the more prolific oligomerizer, and also formed amyloid-fibril like structures at acidic pH and elevated concentrations. Our results suggest the peptides perturb membranes not through pore-like structures, but possibly by a thinning mechanism. | Lactalbumin |
Creatine kinase (CK) MB and lactate dehydrogenase (LDH) isoenzyme 1 are not heart-specific. By contrast, the regulatory proteins troponin I and troponin T are expressed in three different isoforms, one for slow-twitch skeletal muscle fibers, one for fast-twitch skeletal muscle fibers, and one for cardiac muscle (cTnI, cTnT). cTnI and cTnT are usually not detectable in patients without myocardial damage, which is a prerequisite for high diagnostic performance. After acute myocardial infarction (AMI) cTnI, cTnT, and CKMB mass have a comparable early sensitivity. cTnI and cTnT usually peak in parallel except for patients without reperfusion in whom cTnI peaks about 1 day and cTnT approximately 3-4 days after onset of AMI. Both stay increased for at least 4-5 days. cTnT tends to stay increased longer than cTnI. Because the sensitivities of cTnI and cTnT for myocardial injury are comparable, their specificities are the main topic of current debate. Recent reports on mismatches of cTnI and cTnT in patients with renal failure and myopathy without other evidence for myocardial injury suggest that cTnT could be reexpressed similar to CKMB and LDH-1 in chronically damaged human skeletal muscle. In contrast to cTnT, CKMB, and LDH-1, cTnI is not expressed in skeletal muscle during fetal development. So far, an increase in cTnI has been reported only after myocardial damage. Because of currently higher costs, troponin measurement should be restricted at present to clinical settings that really require their high specificity. Based on its distinct functional association with the metabolism of acute ischemic myocardium and according to initial clinical results, glycogen phosphorylase isoenzyme BB is a promising enzyme for the early detection of ischemic myocardial damage. | Troponin |
BACKGROUND: Onconeural antibodies are strongly associated with cancer and paraneoplastic neurological syndromes (PNS). Most of these antibodies are well-characterized (antibodies against Hu, Yo, Ri, CRMP5, amphiphysin, Ma2 and Tr) and are in common use for the diagnosis of definite PNS. MATERIALS AND METHODS: Literature on detection and clinical significance of onconeural antibodies were identified by using relevant search terms in PubMed and reviewed. CONCLUSIONS: The onconeural antibodies are directed against intracellular antigens and their pathogenic role is still largely unknown. They are highly specific markers of paraneoplastic aetiology in patients with neurological symptoms. Detection of an onconeural antibody in a patient with neurological symptoms should lead to prompt investigation for cancer. However, absence of detectable onconeural antibodies does not exclude the PNS diagnosis. In particular, failure to detect antibodies in patients without classical PNS symptoms may result in less vigorous cancer screening and diagnostic delay. Neuronal antibodies that are directed to synaptic proteins or proteins of the cell membrane are also associated with neurological symptoms, and probably have pathogenic effects. The association between these antibodies and cancer is less robust, and they are usually not included among the onconeural antibodies. | Antibodies, Neoplasm |
BACKGROUND: New voluntary standards in the United States regarding bacterial contamination of platelets (PLTs) led to the formation of the AABB Interorganizational Task Force on Bacterial Contamination of Platelets. This article summarizes a survey conducted by the Task Force to assess the impact of bacterial detection. STUDY DESIGN AND METHODS: An Internet-based survey of AABB member institutions was conducted from September 17, 2004, to October 1, 2004. The survey was designed principally to assess PLT usage, supply, and outdating and the currently used bacteria detection methods. RESULTS: Of 900 facilities surveyed, 350 responded (38%). These facilities collected approximately 43.3 and 65.9 percent and transfused approximately 19.1 and 22.2 percent of the whole blood-derived PLT concentrates (WBPCs) and apheresis PLTs in the United States, respectively. Most facilities (64-91%) indicated that their ability to provide PLTs for transfusion had not been affected. Approximately half (50-57.1%) indicated no changes in their PLT inventory. Two-thirds (66-68%) indicated no increased PLT outdating. More than 90 percent of apheresis PLTs are tested with a culture-based method, whereas WBPCs are tested with a variety of methods (mostly non-culture-based) resulting in a 4.6-fold decrease in the confirmed positive detection rate compared with apheresis PLTs (p < 0.001). CONCLUSION: After the implementation of AABB Standard 5.1.5.1, the majority of facilities responding to this survey experienced no (or modest) impact on PLT availability or outdating. Nevertheless, a substantial portion of facilities experienced both increased outdating and decreased availability. Some facilities were greatly impacted. Based on the data gathered, it is impossible to conclude whether such shortages resulted from production or distribution problems or were due to decreased shelf life and increased outdates." | United States Dept. of Health and Human Services |
Wolbachia are maternally-inherited bacteria, which can spread rapidly in populations by manipulating reproduction. cifA and cifB are genes found in Wolbachia phage that are responsible for cytoplasmic incompatibility, the most common type of Wolbachia reproductive interference. In this phenomenon, no viable offspring are produced when a male with both cifA and cifB (or just cifB in some systems) mates with a female lacking cifA. Utilizing this feature, we propose new types of toxin-antidote gene drives that can be constructed with only these two genes in an insect genome, instead of the whole Wolbachia bacteria. By using both mathematical and simulation models, we found that a drive containing cifA and cifB together creates a confined drive with a moderate to high introduction threshold. When introduced separately, they act as a self-limiting drive. We observed that the performance of these drives is substantially influenced by various ecological parameters and drive characteristics. Extending our models to continuous space, we found that the drive individual release distribution has a critical impact on drive persistence. Our results suggest that these new types of drives based on Wolbachia transgenes are safe and flexible candidates for genetic modification of populations." | Symbiont Induced Cytoplasmic Incompatibility |
The increasing demand for using competent and inexpensive methods based on biomaterials, like adsorption and biosorption, has given rise to the low-priced alternative biosorbents. In the past few years, Moringa oleifera (MO) has emerged as a green and low-priced biosorbent for the treatment of contaminated waters with heavy metals and dyes, and given its availability, we can create another generation of effective biosorbents based on different parts of this plant. In this review paper, we have briefed on the application of MO as a miraculous biosorbent for water purification. Moreover, the primary and cutting-edge methods for the purification and modification of MO to improve its adsorption are discussed. It was found that MO has abundant availability in the regions where it is grown, and simple chemical treatments increase the effectiveness of this plant in the treatment of some toxic contaminants. The different parts of this miraculous plant's seeds, leaves, or even husks" in their natural form also possess appreciable sorption capacities, high efficiency for treating low metal concentrations, and rapid adsorption kinetics. Thus, the advantages and disadvantages of different parts of MO as biosorbent, the conditions favorable to this biosorption, also, the proposal of a logical mechanism, which can justify the high efficiency of this plant, are discussed in this review. Finally, several conclusions have been drawn from some important works and which are examined in this review, and future suggestions are proposed." | Moringa |
Angiokeratoma is a benign cutaneous lesion of capillaries. It is characterized by large dilated blood vessels in the superficial dermis and hyperkeratosis of extremities. It is mostly seen in generalized form affecting the extremity of the body, but we report this case of solitary angiokeratoma of the tongue which is a very rare type. | Angiokeratoma |
In this study, we examined the thermal physiology of the endangered New Zealand rockwren (Xenicus gilviventris), a member of the Acanthisittidae, a family unique to New Zealand. This family, derived from Gondwana, is thought to be the sister taxon to all other passerines. Rockwrens permanently reside above the climatic timberline at altitudes from 1000 to 2900 m in the mountains of South Island. They feed on invertebrates and in winter face ambient temperatures far below freezing and deep deposits of snow. Their body temperature and rate of metabolism are highly variable. The rockwrens in our study regulated their body temperature at ca. 36.4 degrees C, which in one individual decreased to 33.1 degrees C at an ambient temperature of 9.4 degrees C; its rate of metabolism decreased by 30% and its body temperature then spontaneously returned to 36 degrees C. The rate of metabolism in a second individual twice decreased by 35%, nearly to the basal rate expected from its mass without a decrease in body temperature. The New Zealand rockwren's food habits, entrance into torpor and continuous residence in a thermally demanding environment suggest that it may hibernate. However, for that conclusion to be accepted, evidence of its use of torpor for extended periods is required. Acanthisittids are distinguished from other passerines by the combination of their permanent temperate distribution, thermal flexibility and a propensity to evolve a flightless condition. These characteristics may principally reflect their geographical isolation in a temperate environment isolated from Gondwana for 82 million years in the absence of mammalian predators. | Body Temperature |
Copy number variants represent an important cause of neurodevelopmental disorders including epilepsy, which is genetically determined in 40% of cases. Epilepsy is caused by chromosomal imbalances or mutations in genes encoding subunits of neuronal voltage- or ligand-gated ion channels or proteins related to neuronal maturation and migration during embryonic development. Here, we report on a girl with mild intellectual disability and idiopathic partial epilepsy. Array-CGH analysis showed a 1.040 Mb de novo interstitial deletion at 9q21.13 band encompassing only four genes, namely RORB, TRPM6, NMRK1, OSTF1, two open reading frames (C9orf40, C9orf41), and a microRNA (MIR548H3). RORB encodes a nuclear receptor highly expressed in the retina, cortex, and thalamus. We hypothesize its role in producing the phenotype of our patient and compare this case with other ones previously reported in the literature to better identify a genotype-phenotype correlation." | Nuclear Receptor Subfamily 1, Group F, Member 2 |
PURPOSE OF REVIEW: To discuss our evolving knowledge about the genetic variations in human tryptase and recent advances in associated clinical phenotypes. RECENT FINDINGS: Hereditary alpha-tryptasemia (HAT) is an autosomal dominant genetic trait and a common cause of elevated basal serum tryptase (BST) in Western populations. It is a risk factor for severe anaphylaxis and an established modifier of mast cell mediator-associated symptoms among patients with systemic mastocytosis (SM). SUMMARY: The unique properties of naturally occurring alpha/beta-tryptase heterotetramers may explain certain elements of phenotypes associated with HAT. Understanding the physiology of tryptases and how this may relate to the clinical features associated with HAT is the first step in identifying optimal medical management and targets for novel therapeutics. | Tryptases |
beta-Lactam antibiotics are the most frequently prescribed antibiotics worldwide. Therefore, it is not surprising that resistance to this very important class of agents poses an increasingly complex and perplexing problem for physicians. Among the variety of mechanisms that can provide resistance to beta-lactam antibiotics in gram-negative bacilli, the production of beta-lactamase is by far the single most important factor. With the introduction of newer beta-lactam agents observed changes in beta-lactamases include the increased prevalence of older enzymes, the appearance of new enzymes, and alteration in the level of expression of the enzymes. These changes have been responsible for resistance to newer cephalosporins, monobactams, carbapenems, and beta-lactamase inhibitor/beta-lactam drug combinations. Resistance to beta-lactam antibiotics has also emerged through alterations in the targets of the drugs, the penicillin-binding proteins, and through alterations in outer membrane permeability of the organisms to the drugs. With some beta-lactam agents, multiple mechanisms must be acquired before clinically relevant levels of resistance are attained. This is especially true for carbapenems and fourth generation cephalosporins. Nevertheless, resistance to beta-lactam antibiotics is on the rise among clinical isolates of gram-negative bacilli, and only through more judicious use of these agents can their usefulness for treatment and prevention of infections be preserved. | beta-Lactam Resistance |
This study presents the first ultra-high performance supercritical fluid chromatography-diode array detector (UHPSFC-DAD) assay for simultaneous quantitation of secoiridoids, iridoids, xanthones, and xanthone glycosides in Gentiana lutea L. Separation was reached within 12 min on an Acquity UPC(2) BEH 2-EP column using CO(2) and methanol with 5.5% water as mobile phases. Method validation for nine selected marker compounds (gentisin, isogentisin, swertiamarin, sweroside, gentiopicroside, loganic acid, amarogentin, gentioside, and its isomer) confirmed the assay's sensitivity, linearity, precision, and accuracy. The practical applicability was proven by the analysis of 13 root specimens and 10 commercial liquid preparations (seven liqueurs and three clear spirits). In all root batches, the secoiridoid gentiopicroside dominated (2.1-5.6%) clearly over all other metabolites. In the liqueurs, the metabolite content and distribution were extremely variable: while gentiopicroside was the main compound in four liqueurs, sweroside dominated in one preparation and loganic acid in two others. In contrast, measurable amounts of the metabolites were not detected in any of the examined clear spirits. | Gentianaceae |
Sida cordifolia L. (Sida) is an annual invasive plant that remains underutilized in Niger. The goal of this study was to characterize the thermal decomposition of Sida for its valorisation as a source of energy through thermogravimetric analysis (TGA). TGA was carried out under nitrogen and air atmospheres. Thus, five different heating rates were used as 10, 20, 30, 40, 50 degrees C min(-1). Kinetic and thermodynamic parameters were determined by isoconversional models of Kissenger-Akahira-Sunose (KAS) and Flynn-Wall-Ozawa (FWO). The results showed that the average activation energy (Ea) of Sida calculated by KAS and FWO in pyrolysis was found to be 74.74 and 80.74 kJ mol(-1) respectively, while it was 51.08 and 58.91 kJ mol(-1) in combustion respectively. Kinetic and thermodynamic parameters such as Ea, DeltaH, DeltaS, and DeltaG obtained by KAS and FWO show that Sida is a remarkable feedstock for bioenergy. | Pyrolysis |
Landfills have been extensively used as waste deposits in most of the big cities in the world. Therefore, considerably large urban areas have contamination threats. Engineering solutions applied to prevent or contain soil, and water contamination often involve the application of liners, which are low permeability barriers made of materials such as compacted clay and geomembranes. In many liner applications, once reduced rates of seepage are expected, diffusion has proved to be relevant, if not dominant, to the process of contaminant transport. Normally, diffusivity parameters can be assessed by a single-reservoir pure diffusion test, where a contaminant solution is placed above a saturated soil sample and the solution's concentration is monitored over time. Once the temporal variation of concentration is measured, the process of back-calculating diffusivity parameters is not standardized. In this paper, an analytical model of the diffusive transport of contaminants is revisited considering the initial and boundary conditions of the pure diffusion test. In this model, the contaminant solution reservoir is included in the analysis domain as an equivalent contaminated soil layer. The analytical solution relies on a series evaluation, which may be a drawback to everyday engineering situations. Therefore, we build a high-accuracy exponential approximation to the solution. Expedited evaluation procedures are proposed to provide reasonable estimates for the fitting parameters. Also, in order to illustrate the applicability of the new solution, test datasets of a soil around the Jockey Club Landfill (JCL) site, one of the major landfills in Latin America, have been modeled. We discuss possible issues of considering linear isotherms to model the sorption characteristics of soils, indicating that convex isotherms, if linearly modeled, may lead to overestimated values of the diffusivity parameter. | Public Health Practice |
The present article provides an overview of the chemical and physical features of haze in China, focusing on the relationship between haze and atmospheric fine particles, and the formation mechanism of haze. It also summarizes several of control technologies and strategies to mitigate the occurrence of haze. The development of instruments and the analysis of measurements of ambient particles and precursor concentrations have provided important information about haze formation. Indeed, the use of new instruments has greatly facilitated current haze research in China. Examples of insightful results include the relationship between fine particles and haze, the chemical compositions and sources of particles, the impacts of the aging process on haze formation, and the application of technologies that control the formation of haze. Based on these results, two relevant issues need to be addressed: understanding the relationship between haze and fine particles and understanding how to control PM2.5. | Particulate Matter |
Benzaldehyde dehydrogenase I was purified from Acinetobacter calcoaceticus by DEAE-Sephacel, phenyl-Sepharose and f.p.l.c. gel-filtration chromatography. The enzyme was homogeneous and completely free from the isofunctional enzyme benzaldehyde dehydrogenase II, as judged by denaturing and non-denaturing polyacrylamide-gel electrophoresis. The subunit Mr value was 56,000 (determined by SDS/polyacrylamide-gel electrophoresis). Estimations of the native Mr value by gel-filtration chromatography gave values of 141,000 with a f.p.l.c. Superose 6 column, but 219,000 with Sephacryl S300. Chemical cross-linking of the enzyme subunits indicated that the enzyme is tetrameric. Benzaldehyde dehydrogenase I was activated more than 100-fold by K+, Rb+ and NH4+, and the apparent Km for K+ was 11.2 mM. The pH optimum in the presence of K+ was 9.5 and the pI of the enzyme was 5.55. The apparent Km values for benzaldehyde and NAD+ were 0.69 microM and 96 microM respectively, and the maximum velocity was approx. 110 mumol/min per mg of protein. Various substituted benzaldehydes were oxidized at significant rates, and NADP+ was also used as cofactor, although much less effectively than NAD+. Benzaldehyde dehydrogenase I had an NAD+-activated esterase activity with 4-nitrophenol acetate as substrate, and the dehydrogenase activity was inhibited by a range of thiol-blocking reagents. The absorption spectrum indicated that there was no bound cofactor or prosthetic group. Some of the properties of the enzyme are compared with those of other aldehyde dehydrogenases, specifically the very similar isofunctional enzyme benzaldehyde dehydrogenase II from the same organism." | Benzaldehyde Dehydrogenase (NADP+) |
Many ecological aspects of tool-use in sea otters are similar to those in Indo-Pacific bottlenose dolphins. Within an area, most tool-using dolphins share a single mitochondrial haplotype and are more related to each other than to the population as a whole. We asked whether sea otters in California showed similar genetic patterns by sequencing mitogenomes of 43 otters and genotyping 154 otters at 38 microsatellite loci. There were six variable sites in the mitogenome that yielded three haplotypes, one found in only a single individual. The other two haplotypes contained similar percentages (33 and 36%) of frequent tool-users and a variety of diet types. Microsatellite analyses showed that snail specialists, the diet specialist group that most frequently used tools, were no more related to each other than to the population as a whole. The lack of genetic association among tool-using sea otters compared with dolphins may result from the length of time each species has been using tools. Tool-use in dolphins appears to be a relatively recent innovation (less than 200 years) but sea otters have probably been using tools for many thousands or even millions of years. | Otters |
Continued use of petroleum sourced fuels is now widely recognized as unsustainable because of depleting supplies and the contribution of these fuels to the accumulation of carbon dioxide in the environment. Renewable, carbon neutral, transport fuels are necessary for environmental and economic sustainability. Biodiesel derived from oil crops is a potential renewable and carbon neutral alternative to petroleum fuels. Unfortunately, biodiesel from oil crops, waste cooking oil and animal fat cannot realistically satisfy even a small fraction of the existing demand for transport fuels. As demonstrated here, microalgae appear to be the only source of renewable biodiesel that is capable of meeting the global demand for transport fuels. Like plants, microalgae use sunlight to produce oils but they do so more efficiently than crop plants. Oil productivity of many microalgae greatly exceeds the oil productivity of the best producing oil crops. Approaches for making microalgal biodiesel economically competitive with petrodiesel are discussed. | Energy-Generating Resources |
The tRNA modification m1G37, introduced by the tRNA methyltransferase TrmD, is thought to be essential for growth in bacteria because it suppresses translational frameshift errors at proline codons. However, because bacteria can tolerate high levels of mistranslation, it is unclear why loss of m1G37 is not tolerated. Here, we addressed this question through experimental evolution of trmD mutant strains of Escherichia coli. Surprisingly, trmD mutant strains were viable even if the m1G37 modification was completely abolished, and showed rapid recovery of growth rate, mainly via duplication or mutation of the proline-tRNA ligase gene proS. Growth assays and in vitro aminoacylation assays showed that G37-unmodified tRNAPro is aminoacylated less efficiently than m1G37-modified tRNAPro, and that growth of trmD mutant strains can be largely restored by single mutations in proS that restore aminoacylation of G37-unmodified tRNAPro. These results show that inefficient aminoacylation of tRNAPro is the main reason for growth defects observed in trmD mutant strains and that proS may act as a gatekeeper of translational accuracy, preventing the use of error-prone unmodified tRNAPro in translation. Our work shows the utility of experimental evolution for uncovering the hidden functions of essential genes and has implications for the development of antibiotics targeting TrmD. | RNA, Transfer, Pro |
Regular measurement and recording of blood pressure, with pulse monitoring and ECG, are the 'minimal monitoring' without which no anaesthetic should take place. This is because blood pressure is an index of some of the most fundamental physiological processes. | Hypotension |
Wrist arteries of 100 patients were percutaneously cannulated with 20-gauge cannulas; pulse-wave recordings and changes in arterial-pressure wave configuration were then used to determine whether a cannulated artery was patent of occluded. At the time of decannulation, 23 of the 100 arteries were thrombosed. Of the three cannula types used in the study, the tapered Medicut was most frequently related to occlusion. Age of patient, trauma to the artery, and duration of the cannulation were not related to later thrombosis. Reversing the direction of the cannula did not change the incidence of thrombosis. Women developed thrombosis twice as frequently as men. A short (+/- 3 cm), small diameter (20 gauge) non-tapered cannula was found most efficient. | Injections, Intra-Arterial |
BACKGROUND: Focal hyperhidrosis can severely affect quality of life. So far, knowledge on the effect of systemic therapy of focal hyperhidrosis is limited. OBJECTIVE: To assess the efficacy and safety of methantheline bromide (MB) in the treatment of axillary and palmar-axillary hyperhidrosis. METHODS: A multicenter controlled randomized double-blind clinical trial was conducted in patients with axillary or palmar-axillary hyperhidrosis defined by a sweat production >50 mg/5 min. Patients received 3 x 50 mg MB daily or placebo over a period of 28 +/- 1 days. Main outcome criterion was the reduction of sweat as measured by gravimetry on day 28 +/- 1. Quality of life was assessed by Dermatology Life Quality Index (DLQI) and Hyperhidrosis Disease Severity Score (HDSS). RESULTS: A total of 339 patients were randomly assigned to receive MB or placebo. On day 28 +/- 1, the mean axillary sweat production was 99 mg for MB and 130 mg for placebo compared with 168 mg and 161 mg respectively at baseline (P = 0.004). Patient's HDSS score decreased in the MB group from 3.2 to 2.4 compared with 3.2 to 2.7 for placebo (P = 0.002). Similar results could be obtained for the DLQI with 9.7 for MB and 12.2 for placebo, which decreased from 16.4 or 17 respectively (P = 0.003). Tolerability was good for both groups. The most frequent adverse event was dry mouth. CONCLUSION: Fifty milligrams methantheline bromide three times a day is an effective and safe treatment of axillary hyperhidrosis. | Methantheline |
The arsenate, arsenite, and antimonite resistance region of the Staphylococcus xylosus plasmid pSX267 was subcloned in Staphylococcus carnosus. The sequenced DNA region revealed three consecutive open reading frames, named arsR, arsB, and arsC. Expression studies in Escherichia coli with the bacteriophage T7 RNA polymerase-promoter system yielded three polypeptides with apparent molecular weights of 8,000, 35,000, and 15,000, which very likely correspond to ArsR, ArsB, and ArsC, respectively. ArsB was distinguished by its overall hydrophobic character, suggesting a membrane association. The arsenate, arsenite, and antimonite resistance was shown to be inducible by all three heavy metal ions. Inactivation of the first gene, arsR, resulted in constitutive expression of resistance. Similar results were obtained with transcriptional fusions of various portions of the ars genes with a lipase reporter gene, indicating a function of ArsR as a negative regulator of a putative promoter in front of arsR. The inactivation of arsR also resulted in reduction of resistance to arsenite and antimonite, while arsenate resistance was unaffected. The three ars genes conferred arsenite resistance in E. coli and arsenite as well as arsenate resistance in Bacillus subtilis. | Antimony Potassium Tartrate |
Pneumonia of pigs is one of the more important disease factors limiting pig production. Of the varieties of pneumonia affecting this species enzootic pneumonia caused by Mycoplasma spp. is the most common and most important. The major effects of this disease are lowered food conversion ratio and poor weight gain. Deaths are usually the result of secondary infection by necrotising, pus-forming bacteria. Eradication of the disease is expensive and requires depopulation and restocking. Control and treatment by antimicrobial agents is most effective if the drug combination used takes regard of the bacteria complicating the disease on any particular property. Other forms of pneumonia such as those caused by Haemophilus pleuropneumoniae, Salmonella cholerae-suis and Aujeszky's disease virus can be important on individual farms. The role of other agents such as Bordetella bronchiseptica and adenoviruses in respiratory disease of pigs remain to be clarified. | Swine Diseases |
Great progress has been made during the last decades in understanding visual systems of arthropods living today. Thus it seems worthwhile to review what is known about structure and function of the eyes of trilobites, the most important group of marine arthropods during the Paleozoic. There are three types of compound eyes in trilobites. The oldest and most abundant is the so-called holochroal eye. The sensory system represents a typical apposition eye, and all units are covered by one cornea in common. The so-called abathochroal eye (only in eodiscid trilobites) consists of small lenses, each individually covered by a thin cuticular cornea. The schizochroal eye is represented just in the suborder Phacopina, and probably is a highly specialized visual system. We discuss the calcitic character of trilobite lenses, the phylogenetic relevance of the existence of crystalline cones in trilobites, and consider adaptations of trilobite's compound eyes to different ecological constraints. The aim of this article is to give a resume of what is known so far about trilobite vision, and to open perspectives to what still might be done. | Compound Eye, Arthropod |
Thirty-one patients (58 eyes) with either primary open angle glaucoma (19 patients with 34 eyes) or suspected glaucoma (12 patients with 24 eyes) were treated for a period of 7 months with only guanethidine 1% and epinephrine 0.2% in one eyedrop (GA-weak) twice daily. The intraocular pressure (IOP) was controlled in 64% of all eyes with an average pressure decrease of 8.4 mm Hg or 31% (p < 0.005). Tonography revealed that the decrease in IOP was due both to inhibition of aqueous humour production (26%, p < 0.005) and to an increase in outflow facility (32%, p < 0.005), showing supersensitivity to inflow and outflow for epinephrine 0.2%, 8 patients were eliminated from the study due to tolerance for the drug. The side-effects were mild and did not lead to cessation of treatment. GA-weak was found to be an effective agent in the management of glaucoma. The treatment was well tolerated by the patients. | Guanethidine |
Impulsiveness and impaired impulse control are connected with an increasing number of psychic disorders. While impulsiveness presents an enduring, pervasive predisposition of personality, the DSM-IV category of "impulse control disorder not elsewhere classified" is operationalized by specific dysfunctional behaviors. So far, the construction of impulsiveness has really not been sufficiently clarified. What does it means and how can one describes it. Different means of conceptualization are presented from a psychological and psychopathological point of view. Their critical review leads to the hypothesis that impulsiveness subsumes a specific quality of drive, on the one hand, which is closely related to a person's temperament and control mechanisms on the other. Drive and impulse control represent enduring traits that act on all levels of personality function, including behavior, cognitive processing and affect regulation. Finally, a model of impulsiveness is suggested that reflects the close interactions among drive, affect and cognition in the regulation of behavior." | Disruptive, Impulse Control, and Conduct Disorders |
OBJECTIVE: This study aimed to systematically evaluate and conduct a meta-analysis of the efficacy and safety of carbon ion radiotherapy for bone sarcomas. METHODS: We searched for articles using the PubMed, Embase, Cochrane Library, and the Web of Science databases from their inception to January 12, 2022. Two researchers independently screened the literature and extracted data based on the inclusion and exclusion criteria. Statistical analyses were performed using STATA version 14.0. RESULTS: We searched for 4378 candidate articles, of which 12 studies were included in our study according to the inclusion and exclusion criteria. Of the 897 BSs patients who received carbon ion radiotherapy in the studies, 526 patients had chordoma, 255 patients had chondrosarcoma, 112 patients had osteosarcoma, and 4 patients had other sarcomas. The local control rate at 1, 2, 3, 4, 5, and 10 years in these studies were 98.5% (95% confidence interval [CI] = 0.961-1.009, I(2) = 0%), 85.8% (95% CI = 0.687-1.030, I(2) = 91%), 86% (95% CI = 0.763-0.957, I(2) = 85.3%), 91.1% (95% CI = 0.849-0.974), 74.3% (95% CI = 0.666-0.820, I(2) = 85.2%), and 64.7% (95% CI = 0.451-0.843, I(2) = 95.3%), respectively. The overall survival rate at 1, 2, 3, 4, 5, and 10 years in these studies were 99.9% (95% CI = 0.995-1.004, I(2) = 0%), 89.6% (95% CI = 0.811-0.980, I(2) = 96.6%), 85% (95% CI = 0.750-0.950, I(2) = 89.4%), 92.4% (95% CI = 0.866-0.982), 72.7% (95% CI = 0.609-0.844, I(2) = 95.3%), and 72.1% (95% CI = 0.661-0.781, I(2) = 46.5%), respectively. Across all studies, the incidence of acute and late toxicities was mainly grade 1 to grade 2, and grade 1 to grade 3, respectively. CONCLUSION: As an advanced radiotherapy, carbon ion radiotherapy is promising for patients with bone sarcomas that are unresectable or residual after incomplete surgery. The data indicated that carbon ion radiotherapy was safe and effective for bone sarcomas, showing promising results for local control, overall survival, and lower acute and late toxicity. PROSPERO REGISTRATION NUMBER: CRD42021258480. | Heavy Ion Radiotherapy |
Myxococcus xanthus is a gliding bacterium that contains two motility systems: S-motility, powered by polar type IV pili, and A-motility, powered by uncharacterized motors and adhesion complexes. The localization and coordination of the two motility engines is essential for directed motility as cells move forward and reverse. During cell reversals, the polarity and localization of motility proteins are rapidly inverted, rendering this system a fascinating example of dynamic protein localization. | Myxococcales |
We hereby report a case presenting a rare form of secondary syphilis with an unusual nodular eruption accompanied by pruritus and generalized lymphadenopathy, bearing a striking resemblance to lymphoma. The histologic picture was also misleading and was compatible with lymphocytoma cutis. The diagnosis was eventually made after results of serologic tests for syphilis were found to be positive, with an extremely high titer of VDRL, and dark-field microscopy had demonstrated spirochetes in a nodular lesion. Secondary syphilis should thus be considered in the differential diagnosis of nodular lesions resembling lymphoreticular disease. It is also suggested that syphilis be added to the list of diagnoses belonging to the category of pseudolymphoma. | Syphilis, Cutaneous |
BACKGROUND: The Magnetic Navigation System (MNS) catheter was shown to be stable in the presence of significant cardiac wall motion and delivered more effective lesions compared to manual control. This stability could potentially make AV junctional re-entrant tachycardia (AVNRT) ablation safer. The aim of this study is to describe the method of mapping and ablation of AVNRT with MNS and 3-D electro-anatomical mapping system (CARTO, Biosense Webster, Diamond bar, CA, USA) anatomical mapping, with a view to improve the safety of ablation. METHODS: The method of precise mapping and ablation with MNS is described. Consecutive AVNRT cases (n=30) from 2012 January to 2015 November, in which magnetic navigation was used, are analysed. RESULTS: Ablation was successful in 27 (90%) out of 30 patients. In three cases, ablation was abandoned due to the proximity of the three-dimensional His image to the potential ablation site. No complications, including AV nodal injury, occurred. The distance from the nearest His position to successful ablation site in both LAO and RAO projections of CARTO images was 26.4+/-8.8 and 27+/-7.7mm respectively. Only in two (9%) patients, ablation needed to be extended superior to the plane of coronary sinus ostium, towards the His bundle region, to achieve slow pathway modification. CONCLUSION: AVNRT ablation with MNS allows for accurate mapping of the AV node and stable ablation at a safe distance, which could help avoid AV nodal injury. We recommend this modality for younger patients with AVNRT." | Tachycardia, Atrioventricular Nodal Reentry |
Candida albicans is one of the most important causes of life-threating fungal infections. Lanosterol 14alpha-demethylase (Cytochrome P450DM) is the target enzyme of azole antifungal agents. The study involved selection and modeling of the target enzyme followed by refinement of the model using molecular dynamic simulation. The modeled structure of enzyme was validated using Ramachandran plot and Sequence determination technique. A series of chlorosubstituted imidazole analogues were evaluated for Cytochrome P450 inhibitory activity using molecular docking studies. The imidazole analogues were prepared using Chem sketch and molecular docking was performed using Molergo Virtual Docker program. The docking study indicated that all the imidazole analogues (AN1-AN45) and standard drugs i.e., Ketoconazole, Clotrimazole and Miconazole have interaction with protein residue of 14alpha-demethylase, Heme cofactor and the water molecules present in the active site. | Cytochrome P450 Family 51 |
There was the 100th anniversary of the birth of Peter Semenovich Babkin, a front-line soldier, famous neurologist, clinician, scientist and educator, Professor, Doctor of Medical Sciences, the founder of the theory of intrapartum fetal hibernation and maternal autoanalgesia. | Neurologists |
Heavy menstrual bleeding, or menorrhagia, is subjectively defined as a complaint of a large amount of bleeding during menstrual cycles that occurs over several consecutive cycles" and is objectively defined as menstrual blood loss of more than 80 mL per cycle that is associated with an anemia status (defined as a hemoglobin level of <10 g/dL). During their reproductive age, more than 30% of women will complain of or experience a heavy amount of bleeding, which leads to a debilitating health outcome, including significantly reduced health-related quality of life, and a considerable economic burden on the health care system. Although surgical treatment might be the most important definite treatment, especially hysterectomy for those women who have finished bearing children, the uterus is still regarded as the regulator and controller of important physiological functions, a sexual organ, a source of energy and vitality, and a maintainer of youth and attractiveness. This has resulted in a modern trend in which women may reconsider the possibility of organ preservation. For women who wish to retain the uterus, medical treatment may be one of the best alternatives. In this review, recent trends in the management of women with heavy menstrual bleeding are discussed." | Menorrhagia |
Blockade of the immunosuppressive checkpoint receptors cytotoxic T-lymphocyte-associated protein 4 (CTLA4) or programmed death 1 (PD-1) and its cognate ligand, programmed death 1 ligand (PD-L1), has altered the landscape of anti-tumor immunotherapy. B7 family and tumor necrosis factor receptor (TNFR) superfamily play a crucial role in T cell activation, tolerance, and anergy through co-stimulatory and inhibitory signal transduction. Investigating the immune molecular landscapes of the B7 and TNFR families is critical in defining the promising responsive candidates. Herein, we performed comprehensive alteration analysis of the B7 and TNFR family genes across six hepatocellular carcinoma (HCC) datasets with over 1000 patients using cBioPortal TCGA data. About 16% of patients had both B7 and TNFR gene alterations. TNFR gene amplifications were relatively more common (1.73(-)8.82%) than B7 gene amplifications (1.61(-)2.94%). Analysis of 371 sequenced samples revealed that all genes were upregulated: B7 and TNFR mRNA were upregulated in 23% of cases (86/371) and 28% of cases (105/371), respectively. Promoter methylation analysis indicated an epigenetic basis for B7 and TNFR gene regulation. The mRNA levels of B7 and TNFR genes were inversely correlated with promoter methylation status. B7-H6 expression was significantly associated with worse overall survival, and B7-H6 mRNA was increased gradually in cases with gene copy number alterations. B7-H6 overexpression was associated with aggressive clinicopathologic features and poor prognosis in HCC. Downregulation of B7-H6 in HCC cells significantly inhibited cell adhesion, proliferation, migration, and invasion. Knockdown of B7-H6 in HCC cells inhibited tumor growth and metastasis in vivo. B7-H6 promoted HCC metastasis via induction of MMP-9 expression and STAT3 activation. B7-H6 and STAT3 performed functional overlapping roles on enhancing the MMP-9 promoter activity in HCC cells. These results suggest that alterations of the immunologic co-stimulator B7 and TNFR families correlate with HCC metastasis and prognosis, and especially B7-H6 plays a critical role in promoting metastasis of HCC. | B7 Antigens |
Why, in all cultures in which hearing is possible, has language become the province of speech and the oral modality? I address this question by widening the lens with which we look at language to include the manual modality. I suggest that human communication is most effective when it makes use of two types of formats--a discrete and segmented code, produced simultaneously along with an analog and mimetic code. The segmented code is supported by both the oral and the manual modalities. However, the mimetic code is more easily handled by the manual modality. We might then expect mimetic encoding to be done preferentially in the manual modality (gesture), leaving segmented encoding to the oral modality (speech). This argument rests on two assumptions: (1) The manual modality is as good at segmented encoding as the oral modality; sign languages, established and idiosyncratic, provide evidence for this assumption. (2) Mimetic encoding is important to human communication and best handled by the manual modality; co-speech gesture provides evidence for this assumption. By including the manual modality in two contexts--when it takes on the primary function of communication (sign language), and when it takes on a complementary communicative function (gesture)--in our analysis of language, we gain new perspectives on the origins and continuing development of language. | Manual Communication |
PURPOSE: To explore the expression level and prognostic value of ADAMTS9-AS2 in prostate cancer (PCa). METHODS: ADAMTS9-AS2 levels in 110 paired PCa tissues and adjacent normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between ADAMTS9-AS2 level and clinical parameters of PCa was analyzed. ROC (receiver operating characteristics) curves were depicted for assessing the diagnostic value of ADAMTS9-AS2 in PCa. Through collecting 5-year follow-up data of PCa patients, survival analysis was performed by Kaplan-Meier method. Finally, Cox regression model was used to analyze factors affecting outcomes of PCa patients. RESULTS: ADAMTS9-AS2 was downregulated in PCa tissues than in adjacent normal ones. Its level was lower in PCa tissues with clinical stage III+IV or tumor size >/=3cm compared to those with stage I+II or tumor size <3cm. ROC curves verified the diagnostic value of ADAMTS9-AS2 in PCa (AUC=0.902, cut-off value=0.40, sensitivity=90.00%, specificity=79.09%, Youden index=0.6909). Kaplan-Meier method and log-rank test uncovered worse prognosis in PCa patients expressing low level of ADAMTS9-AS2. Clinical stage, tumor size and ADAMTS9-AS2 level were independent factors influencing prognosis of PCa. CONCLUSIONS: ADAMTS9-AS2 is downregulated in PCa and its low level is unfavorable to the disease prognosis. ADAMTS9-AS2 may be utilized as a potential diagnostic and prognostic hallmark of PCa. | ADAMTS9 Protein |
In this article we describe a technique of needle dermabrasion (tattoo without pigment) used to improve achromic, hypertrophic, and unsightly scars. It is simple, safe (no complications), and it gives us consistently good results. | Dermabrasion |
A series of benzylaminoimidazoline derivatives was synthesized and evaluated for norepinephrine transporter (NET) targeting. Among them, N-(3-iodobenzyl)-4,5-dihydro-1H-imidazol-2-amine (Compound 9) displayed the highest affinity for NET (IC(50) = 5.65 +/- 0.97 muM). The corresponding radiotracer [(125) I]9 was further prepared by copper-mediated radioiodination and evaluated both in vitro and in vivo. The cellular uptake results suggested that [(125) I]9 was specifically taken up by the NET-expressing SK-N-SH cell line. Biodistribution studies showed that [(125) I]9 accumulated in the heart (5.54 +/- 1.24 %ID/g at 5 min p.i. and 0.79 +/- 0.08 %ID/g at 2 h p.i.) and adrenal gland (14.83 +/- 3.47 %ID/g at 5 min p.i. and 3.87 +/- 0.24 %ID/g at 2 h p.i.). The uptake in the heart and adrenal gland could be significantly inhibited by preinjection of desipramine (DMI). These results indicated that the benzylaminoimidazoline derivatives retained affinity for NET, which could provide structure-activity relationship data for further studies." | Norepinephrine Plasma Membrane Transport Proteins |
BACKGROUND AND AIMS: Endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is increasingly being performed at tertiary and community centers. While it has been suggested that these patients should be evaluated at expert centers, the impact of this practice has not been evaluated. We aimed to assess the impact of referral of BE-related neoplasia patients to expert centers by assessing the proportion of patients with change in pathological diagnosis and visible lesions detected. METHODS: Multiple databases were searched until December 2021 for studies of patients with BE referred from the community to expert center. The proportions of pathology grade change and newly detected visible lesions at expert centers were pooled using a random-effects model. Subgroup analyses were performed based on baseline histology and other relevant factors. RESULTS: Twelve studies were included (1630 patients). The pooled proportion of pathology grade change after expert pathologist review was 47% (95% CI 34-59%) overall and 46% (95% CI 31-62%) among patients with baseline low-grade dysplasia. When upper endoscopy was repeated at an expert center, the pooled proportion of pathology grade change was still high 47% (95% 26-69%) overall and 40% (95% CI 34-45%) among patients with baseline LGD. The pooled proportion of newly detected visible lesions was 45% (95% CI 28-63%) and among patients referred with LGD was 27% (95% CI 22-32%). CONCLUSION: An alarmingly high proportion of newly detected visible lesions and pathology grade change were found when patients were referred to expert centers supporting the need for centralized care for BE-related neoplasia patients. | Precancerous Conditions |
The components of the Kangaroo Mother Care (KMC) intervention, their rational bases, and their current uses in low-, middle-, and high-income countries are described. KMC was started in 1978 in Bogota (Colombia) in response to overcrowding and insufficient resources in neonatal intensive care units associated with high morbidity and mortality among low-birthweight infants. The intervention consists of continuous skin-to-skin contact between the mother and the infant, exclusive breastfeeding, and early home discharge in the kangaroo position. In studies of the physiological effects of KMC, the results for most variables were within clinically acceptable ranges or the same as those for premature infants under other forms of care. Body temperature and weight gain are significantly increased, and a meta-analysis showed that the kangaroo position increases the uptake and duration of breastfeeding. Investigations of the behavioral effects of KMC show rapid quiescence. The psychosocial effects of KMC include reduced stress, enhancement of mother-infant bonding, and positive effects on the family environment and the infant's cognitive development. CONCLUSION: Past and current research has clarified some of the rational bases of KMC and has provided evidence for its effectiveness and safety, although more research is needed to clearly define the effectiveness of the various components of the intervention in different settings and for different therapeutic goals. | Infant Care |
The content-dependent activity of surfactant protein (SP)-B was studied in mixtures with dipalmitoyl phosphatidylcholine (DPPC), synthetic lipids (SL), and purified phospholipids (PPL) from calf lung surfactant extract (CLSE). At fixed SP-B content, adsorption and dynamic surface tension lowering were ordered as PPL/SP-B approximately SL/SP-B > DPPC/SP-B. All mixtures were similar in having increased surface activity as SP-B content was incrementally raised from 0.05 to 0.75% by weight. SP-B had small but measurable effects on interfacial properties even at very low levels < or =0.1% by weight. PPL/SP-B (0.75%) had the highest adsorption and dynamic surface activity, approaching the behavior of CLSE. All mixtures containing 0.75% SP-B reached minimum surface tensions <1 mN/m in pulsating bubble studies at low phospholipid concentration (1 mg/ml). Mixtures of PPL or SL with SP-B (0.5%) also had minimum surface tensions <1 mN/m at 1 mg/ml, whereas DPPC/SP-B (0.5%) reached <1 mN/m at 2.5 mg/ml. Physiological activity also was strongly dependent on SP-B content. The ability of instilled SL/SP-B mixtures to improve surfactant-deficient pressure-volume mechanics in excised lavaged rat lungs increased as SP-B content was raised from 0.1 to 0.75% by weight. This study emphasizes the crucial functional activity of SP-B in lung surfactants. Significant differences in SP-B content between exogenous surfactants used to treat respiratory disease could be associated with substantial activity variations." | Pulmonary Surfactant-Associated Protein B |
Inhibition is presumed to play an important role in gustatory processing in the rostral nucleus of the solitary tract (rNST). One source of inhibition, GABA, is abundant within the nucleus and comes both from local, intrasolitary sources and from outside the nucleus. In addition to the receptor-mediated effects of GABA on rNST neurons, the hyperpolarization-sensitive currents, Ih and IA, have the potential to further modulate afferent signals. To elucidate the effects of GABAergic modulation on solitary tract (ST)-evoked responses in phenotypically defined rNST neurons and to define the presence of IA and Ih in the same cells, we combined in vitro recording and optogenetics in a transgenic mouse model. This mouse expresses channelrhodopsin 2 (ChR2) in GAD65-expressing GABAergic neurons throughout the rNST. GABA positive (GABA+) neurons differed from GABA negative (GABA-) neurons in their response to membrane depolarization and ST stimulation. GABA+ neurons had lower thresholds to direct membrane depolarization compared with GABA- neurons, but GABA- neurons responded more faithfully to ST stimulation. Both IA and Ih were present in subsets of GABA+ and GABA- neurons. Interestingly, GABA+ neurons with Ih were more responsive to afferent stimulation than inhibitory neurons devoid of these currents, whereas GABA- neurons with IA were more subject to inhibitory modulation. These results suggest that the voltage-gated channels underlying IA and Ih play an important role in modulating rNST output through a circuit of feedforward inhibition. | Receptors, Purinergic P2X2 |
Pemphigus is a group of autoimmune diseases characterized by flaccid lesions on the skin and mucous membranes. In pemphigus vulgaris, the most common subtype of pemphigus, lesions might be appeared anywhere on the oral mucosa, mostly in the buccal mucosa. However, the gingiva is a less frequently affected site. Here, we performed a retrospective study at Tehran University of Medical Sciences, covering a two-year period to identify pemphigus patients with active lesions confined to the gingiva. Considering 1787 initially evaluated pemphigus cases, 512 (28.6%) were found to have a history of gingival involvement. Among them, 31 patients had only gingival involvement during their last visit, including 29 (93.5%) women and only two (6.5%) men. The mean of disease duration in this group was 5.29 +/- 3.46 years, and they had gingival involvement for a mean of 23.9 +/- 19.3 months. Of 28 patients, nine were negative for anti-Dsg3 and 24 were negative for anti-Dsg1. In 24 patients, who received rituximab, the mean pemphigus disease area index specifically for gingiva was 4.76 +/- 0.74 at baseline, which had changed to 4.13 +/- 0.75 and 3.26 +/- 0.63 three and 6 months after rituximab administration, respectively. After 3 months, gingival lesions were either entirely resolved (n = 3), partially resolved (n = 11), remained unchanged (n = 2), or progressed (n = 7). Gingiva-confined presentation of lesions in pemphigus could be non-anti-Dsg1/3 dependent in some patients. Such patients do not respond well to conventional treatments and rituximab therapy. More studies on the pathogenesis of gingiva-confined presentation of pemphigus are required. | Desmoglein 1 |
BACKGROUND: Large number of patients with head-and-neck cancer presents with factors such as advanced disease, poor general condition, and associated comorbidities due to which radical treatment is not recommended in these patients. In this scenario, the aim of the present study is to assess the role and feasibility of hypofractionated palliative radiotherapy in these patients. SUBJECTS AND METHODS: This study was conducted on patients with histopathologically proven cases of squamous cell carcinoma of the head-and-neck region who were surgically unresectable. The quality of life (QOL) was assessed before and after 1 month of radiotherapy using University of Washington Quality of Life questionnaire version 4. All patients received 40 Gy in 10 fractions, twice weekly by two lateral fields covering primary and secondary disease. Response evaluation criteria in solid tumor criteria were used to assess the tumor response. Toxicity was assessed weekly using radiation therapy oncology group criteria. RESULTS: A total of 50 patients were enrolled in this study, out of which 46 completed the planned treatment of 40 Gy in 10 fractions. Common complaints were distressing pain at the primary site (42%), neck swelling (30%), difficult in swallowing (18%), and change in voice (10%). Statistically significant improvements were observed in overall QOL (26.9 +/- 9.63 to 55.65 +/- 19.28) and none of them experienced Grade IV mucositis or skin toxicity. Good objective response was seen in 82.6% and 84.7% of patients at primary and nodal sites, respectively. CONCLUSIONS: This hypofractionated palliative radiotherapy regimen is a good treatment option in patients with Stage IV head-and-neck cancer, who are not fit for treatment with curative intent." | Squamous Cell Carcinoma of Head and Neck |
Throughout evolution, plants have developed the ability to produce secondary phenolic metabolites, which are important for their interactions with the environment, reproductive strategies and defense mechanisms. These (poly)phenolic compounds are a heterogeneous group of natural antioxidants found in vegetables, cereals and leguminous that exert beneficial and protective actions on human health, playing roles such as enzymatic reaction inhibitors and cofactors, toxic chemicals scavengers and biochemical reaction substrates, increasing the absorption of essential nutrients and selectively inhibiting deleterious intestinal bacteria. Polyphenols present in some commodity grains, such as soy and cocoa beans, as well as in other vegetables considered security foods for developing countries, including cassava, taro and beetroot, all of them cropped in Brazil, have been identified and quantified in order to point out their bioavailability and the adequate dietary intake to promote health. The effects of the flavonoid and non-flavonoid compounds present in these vegetables, their metabolism and their effects on preventing chronic and degenerative disorders like cancers, diabetes, osteoporosis, cardiovascular and neurological diseases are herein discussed based on recent epidemiological studies. | Colocasia |
Fibrobacter succinogenes is one of the most pivotal fibrolytic bacterial species in the rumen. In a previous study, we confirmed enhancement of fiber digestion in a co-culture of F. succinogenes S85 with non-fibrolytic ruminal strains R-25 and/or Selenomonas ruminantium S137. In the present study, mRNA expression level of selected functional genes in the genome of F. succinogenes S85 was monitored by real-time RT-PCR. Growth profile of F. succinogenes S85 was similar in both the monoculture and co-cultures with non-fibrolytics. However, expression of 16S rRNA gene of F. succinogenes S85 in the co-culture was higher (P < 0.01) than that of the monoculture. This finding suggests that metabolic activity of F. succinogenes S85 was enhanced by coexistence with strains R-25 and/or S. ruminantium S137. The mRNA expression of fumarate reductase and glycoside hydrolase genes was up-regulated (P < 0.01) when F. succinogenes S85 was co-cultured with non-fibrolytics. These results indicate the enhancement of succinate production and fiber hydrolysis by F. succinogenes S85 in co-cultures of S. ruminantium and R-25 strains. | Fibrobacteres |
AIMS: This study aimed to investigate the effect of replacing plant proteins with animal proteins in the dietary approaches to stop hypertension (DASH) diet on cardiometabolic risk factors in obese metabolic syndrome participants. METHODS: In this double-blind randomized controlled clinical trial, 90 obese patients with metabolic syndrome, aged 30-70 years were randomly allocated into the DASH diet based on plant or animal proteins for 8 weeks. Fasting blood samples were collected to assess the biochemical markers. Also, blood pressure, weight, and waist circumference (WC) were measured at the beginning and end of the trial. RESULTS: The participants in both groups experienced significant reductions in the fasting plasma glucose (FPG), systolic blood pressure (SBP) and diastolic blood pressure (DBP), triglyceride (TG) concentrations, weight and WC. However the reduction in FPG and SBP was higher in the plant-based DASH group, compared to the animal-based DASH group, after adjustment for weight change. No significant changes were found within or between groups with regard to total cholesterol, LDL-C, HDL-C. CONCLUSIONS: Substituting plant proteins with animal proteins in the DASH diet improves FPG and SBP in obese individuals with metabolic syndrome, independent of weight change. IRCT registration number: IRCT20090203001640N16." | Dietary Approaches To Stop Hypertension |
The infectious agent causing epidemic non-A, non-B hepatitis was identified in 1983 from a human challenge experiment. The novel hepatitis E virus (HEV) subsequently was cloned in 1990 and the genome sequenced. HEV transmission is highly endemic in Asia, the Middle East, and Africa. Fecal contamination of drinking water is the most common mode of spread. Although usually asymptomatic, HEV infection can cause fulminant hepatitis. Recent studies indicate that hepatitis E may be a zoonotic disease, with pigs and possibly rats serving as reservoirs for human infection. A recombinant HEV vaccine is currently in phase III clinical trials. The characterization of the major types of viral hepatitis during the last 20 years illustrates how modern genetic technology has revolutionized research in infectious diseases. Within less than two decades of the discovery of HEV, its epidemiology has been described, serologic tests have been developed, and a candidate vaccine has been evaluated in clinical trials. | Endemic Diseases |
AIMS/INTRODUCTION: In this meta-analysis, we aimed to explore the association between bodyweight cycling (weight fluctuation) and the risk of developing diabetes. MATERIALS AND METHODS: We analyzed data from eligible cohort studies that assessed the association between weight cycling in adults and the risk of developing diabetes from online databases PubMed, Cochrane Library and EMBASE databases (1966 to April 2020). We pooled data using relative risks (RRs) with a random effects model. RESULTS: A total of 14 studies involving 253,766 participants, including 8,904 diabetes events, were included. One study included eight independent reports, resulting in 21 reports in 14 studies. Summary analysis showed that individuals who suffered weight cycling had a higher risk of diabetes (RR 1.23. 95% confidence interval 1.07-1.41; P = 0.003). However, the association between weight cycling and the risk of developing diabetes was not observed in obese participants (body mass index >/=30 kg/m(2) ; P = 0.08). CONCLUSIONS: The present meta-analysis showed that weight cycling was a strong independent predictor of new-onset diabetes. Future studies are required to detect the causal links between weight cycling and the risk of developing diabetes. | Weight Cycling |
Neocortical neurons in vivo process each of their individual inputs in the context of ongoing synaptic background activity, produced by the thousands of presynaptic partners a typical neuron has. Previous work has shown that background activity affects multiple aspects of neuronal and network function. However, its effect on the induction of spike-timing dependent plasticity (STDP) is not clear. Here we report that injections of simulated background conductances (produced by a dynamic-clamp system) into pyramidal cells in rat brain slices selectively reduced the magnitude of timing-dependent synaptic potentiation while leaving the magnitude of timing-dependent synaptic depression unchanged. The conductance-dependent suppression also sharpened the STDP curve, with reliable synaptic potentiation induced only when EPSPs and action potentials (APs) were paired within 8 ms of each other. Dual somatic and dendritic patch recordings suggested that the deficit in synaptic potentiation arose from shunting of dendritic EPSPs and APs. Using a biophysically detailed computational model, we were not only able to replicate the conductance-dependent shunting of dendritic potentials, but show that synaptic background can truncate calcium dynamics within dendritic spines in a way that affects potentiation more strongly than depression. This conductance-dependent regulation of synaptic plasticity may constitute a novel homeostatic mechanism that can prevent the runaway synaptic potentiation to which Hebbian networks are vulnerable. | Synaptic Potentials |
Nucleic acid polymerases catalyze the formation of DNA or RNA from nucleoside-triphosphate precursors. Amino acid residues in the active site of polymerases are thought to contribute only indirectly to catalysis by serving as ligands for the two divalent cations that are required for activity or substrate binding. Two proton-transfer reactions are necessary for polymerase-catalyzed nucleotidyl transfer: deprotonation of the 3'-hydroxyl nucleophile and protonation of the pyrophosphate leaving group. Using model enzymes representing all four classes of nucleic acid polymerases, we show that the proton donor to pyrophosphate is an active-site amino acid residue. The use of general acid catalysis by polymerases extends the mechanism of nucleotidyl transfer beyond that of the well-established two-metal-ion mechanism. The existence of an active-site residue that regulates polymerase catalysis may permit manipulation of viral polymerase replication speed and/or fidelity for virus attenuation and vaccine development. | Nucleotidyltransferases |
This is an exciting time for immunology because the future promises to be replete with exciting new discoveries that can be translated to improve health and treat disease in novel ways. Immunologists are attempting to answer increasingly complex questions concerning phenomena that range from the genetic, molecular, and cellular scales to that of organs, whole animals or humans, and populations of humans and pathogens. An important goal is to understand how the many different components involved interact with each other within and across these scales for immune responses to emerge, and how aberrant regulation of these processes causes disease. To aid this quest, large amounts of data can be collected using high-throughput instrumentation. The nonlinear, cooperative, and stochastic character of the interactions between components of the immune system as well as the overwhelming amounts of data can make it difficult to intuit patterns in the data or a mechanistic understanding of the phenomena being studied. Computational models are increasingly important in confronting and overcoming these challenges. I first describe an iterative paradigm of research that integrates laboratory experiments, clinical data, computational inference, and mechanistic computational models. I then illustrate this paradigm with a few examples from the recent literature that make vivid the power of bringing together diverse types of computational models with experimental and clinical studies to fruitfully interrogate the immune system. | Monitoring, Immunologic |
Patient-reported outcome measures (PROMs) assign objective measures to patient's subjective experiences of health, pain, disability, function, and quality of life. PROMs can be useful for providers in shared decision making, outcome assessment, and indicating patients for surgery. In this article, we provide an overview of the legacy PROMs used in spinal care, recent advancements in patient-reported outcomes, and future directions in PROMs. Recent advances in patient-reported outcome assessments have included standardization of measurement tools, integration of data collection into workflow, and applications of outcome measures in predictive models and decision-making tools. Continual appraisal of instruments and incorporation into artificial intelligence and machine learning analytics will continue to augment the delivery of high-value spinal care. | Patient Outcome Assessment |
Wulfenioidones A - K (1-11) were abietane diterpenoids with highly oxidized 6/6/6 aromatic tricyclic skeleton isolated from the whole plant of Orthosiphon wulfenioides, and their planar structures and absolute configurations were elucidated by spectroscopic data interpretation, electronic circular dichroism calculation as well as X-ray crystallography analysis. Bioactivity screening indicated that compounds 1-4, 6 and 8 exhibited lactate dehydrogenase (LDH) inhibition effect with IC(50) values ranging from 0.23 to 3.43 muM by preventing the mononuclear macrophage cell pyroptosis induced by double signal stimulation of LPS and nigericin. Western Blot analyses of Caspase-1 and IL-1beta down-regulation exhibited that compound 1 could selectively inhibit NLRP3 inflammasome, and the cell morphological observation further supported that compound 1 prevented macrophage cell pyroptosis. | Orthosiphon |
In this paper we analyse the structural organization of human apolipoprotein E (apoE) at the surface of triglyceride (TG)-rich lipoproteins, in relation to the metabolic pathway of these particles. ApoE acts as a receptor-binding ligand at the surface of chylomicrons and VLDL (very low density lipoproteins). The degree of exposure of apoE at the surface of lipoproteins and its affinity for the receptor both determine the uptake and catabolism of these lipoproteins. ApoE and/or apoB100, the major apolipoprotein constituent of LDL, contribute to the interaction of lipoproteins with five different cellular receptors: 1) the low density lipoprotein (LDL) receptor; 2) the LDL receptor-related protein (LRP); 3) the macrophage receptor for hypertriglyceridemic VLDL; 4) the scavenger receptor; 5) the VLDL receptor. The degree of exposure of apoE at the surface of normo- and hyperlipidemic VLDL can modulate their uptake by the LDL receptor. Normolipidemic VLDL are poorly recognized by the LDL receptor whereas hypertriglyceridemic VLDL are cleared more efficiently through this pathway. On the other hand, the extent of apoE self-association, which is dependent upon the degree of hydrolysis of the TG-rich particles, can control their interaction with the LDL-receptor related protein. The lateral organization of apoE at the surface of TG-rich particles, its interaction with other apoproteins and its extent of self-association might therefore be important factors in the clearance of these lipoproteins. Finally, structural defects of apoE might result in an impaired interaction of apoE-containing lipoproteins with these receptors and lead to the development of atherogenic dyslipidemias. | Lipoproteins |
Purpose: Experienced homophobia-negative treatment and perceptions that gay, bisexual, and other men who have sex with men (MSM) encounter because of their sexual orientations-may promote HIV infection among MSM. We conducted a rapid review and meta-analysis to examine experienced homophobia in relation to HIV infection risk. Methods: We searched Embase, MEDLINE, PsycINFO, and Sociological Abstracts to acquire data from U.S. studies published during 1992-2017. Studies examined experienced homophobia in relation to sexual risk behavior, poor HIV care continuum engagement, and diagnosed HIV infection. Random-effects models yielded summary odds ratios (ORs) and 95% confidence intervals (CIs). Results: Experienced homophobia was associated with having any sexual risk behavior (OR = 1.33, 95% CI = 1.25-1.42, I(2) = 89.2%), receptive condomless anal sex (CAS) (OR = 1.33, 95% CI = 1.14-1.56, I(2) = 63.6%), HIV-discordant CAS (OR = 1.66, 95% CI = 1.29-2.13, I(2) = 85.3%), an increased number of sex partners (OR = 1.16, 95% CI = 1.13-1.19, I(2) = 0.0%), diagnosed HIV infection (OR = 1.34, 95% CI = 1.10-1.64, I(2) = 86.3%), and poor HIV care continuum engagement among MSM living with HIV (OR = 1.45, 95% CI = 1.02-2.08, I(2) = 47.0%). Effect sizes for any sexual risk behavior were larger in samples with >/=50% Black or Latino (vs. White) MSM and for family-based mistreatment and perceived sexual minority stigma (vs. other homophobia types). Conclusion: Experienced homophobia is associated with HIV infection risk among MSM. Its association with sexual risk behavior may be stronger among Black and Latino (vs. White) MSM and for family-based mistreatment and perceived sexual minority stigma (vs. other homophobia types). Research is needed to better understand causality in these relationships and the role of interventions to reduce homophobia. | Homophobia |
Although easily examined, abnormalities of the tongue can present a diagnostic and therapeutic dilemma for physicians. Recognition and diagnosis require a thorough history, including onset and duration, antecedent symptoms, and tobacco and alcohol use. Examination of tongue morphology and a careful assessment for lymphadenopathy are also important. Geographic tongue, fissured tongue, and hairy tongue are the most common tongue problems and do not require treatment. Median rhomboid glossitis is usually associated with a candidal infection and responds to topical antifungals. Atrophic glossitis is often linked to an underlying nutritional deficiency of iron, folic acid, vitamin B12, riboflavin, or niacin and resolves with correction of the underlying condition. Oral hairy leukoplakia, which can be a marker for underlying immunodeficiency, is caused by the Epstein-Barr virus and is treated with oral antivirals. Tongue growths usually require biopsy to differentiate benign lesions (e.g., granular cell tumors, fibromas, lymphoepithelial cysts) from premalignant leukoplakia or squamous cell carcinoma. Burning mouth syndrome often involves the tongue and has responded to treatment with alpha-lipoic acid, clonazepam, and cognitive behavior therapy in controlled trials. Several trials have also confirmed the effectiveness of surgical division of tongue-tie (ankyloglossia), in the context of optimizing the success of breastfeeding compared with education alone. Tongue lesions of unclear etiology may require biopsy or referral to an oral and maxillofacial surgeon, head and neck surgeon, or a dentist experienced in oral pathology. | Glossitis |
We evaluated the relevance of tests for Human papillomavirus 16 and 18 (HPV-16, HPV-18) in two cervix regions (exocervical and endocervical) separately. The total of 142 cervical smears obtained from 91 women in Slovakia attending onco-gynecological outpatient care were examined for the presence of HPVs by PCR with the general primers GP5 and GP6 (GP5/6). The HPV-positive smears were examined for the presence of HPV-16 and HPV-18 and the results compared with cytological assessment. In 73 HPV-positive smears, the number of cases with detected HPV-16 was about three times higher in exocervix and about two times higher in endocervix in comparison with number of cases with detected HPV-18. In the smears considered as normal by cytology, two times higher occurrence of HPV-18 in endocervical smears was found in comparison with exocervical ones. Eight patients were double-infected with HPV-16 and HPV-18, but no patient was infected with these HPVs in both cervical regions. This finding emphasized the importance of examination of both cervical regions separately. Overlooking of the endocervical canal for the close examination by cytology and PCR might increase the failure to detect HPVs associated with adenocarcinoma. | Human papillomavirus 18 |
The methane-oxidizing bacterium Methylacidimicrobium thermophilum AP8 thrives in acidic geothermal ecosystems that are characterized by high degassing of methane (CH(4)), H(2), H(2)S, and by relatively high lanthanide concentrations. Lanthanides (atomic numbers 57 to 71) are essential in a variety of high-tech devices, including mobile phones. Remarkably, the same elements are actively taken up by methanotrophs/methylotrophs in a range of environments, since their XoxF-type methanol dehydrogenases require lanthanides as a metal cofactor. Lanthanide-dependent enzymes seem to prefer the lighter lanthanides (lanthanum, cerium, praseodymium, and neodymium), as slower methanotrophic/methylotrophic growth is observed in medium supplemented with only heavier lanthanides. Here, we purified XoxF1 from the thermoacidophilic methanotroph Methylacidimicrobium thermophilum AP8, which was grown in medium supplemented with neodymium as the sole lanthanide. The neodymium occupancy of the enzyme is 94.5% +/- 2.0%, and through X-ray crystallography, we reveal that the structure of the active site shows interesting differences from the active sites of other methanol dehydrogenases, such as an additional aspartate residue in close proximity to the lanthanide. Nd-XoxF1 oxidizes methanol at a maximum rate of metabolism (V(max)) of 0.15 +/- 0.01 mumol . min(-1) . mg protein(-1) and an affinity constant (K(m)) of 1.4 +/- 0.6 muM. The structural analysis of this neodymium-containing XoxF1-type methanol dehydrogenase will expand our knowledge in the exciting new field of lanthanide biochemistry. IMPORTANCE Lanthanides comprise a group of 15 elements with atomic numbers 57 to 71 that are essential in a variety of high-tech devices, such as mobile phones, but were considered biologically inert for a long time. The biological relevance of lanthanides became evident when the acidophilic methanotroph Methylacidiphilum fumariolicum SolV, isolated from a volcanic mud pot, could only grow when lanthanides were supplied to the growth medium. We expanded knowledge in the exciting and rapidly developing field of lanthanide biochemistry by the purification and characterization of a neodymium-containing methanol dehydrogenase from a thermoacidophilic methanotroph. | Neodymium |
The nicotinic receptor alpha7nAchR reportedly regulates vagal nerve targets in brain and cardiac tissue. Here we show that nAchR7(-/-) mice exhibit increased bone mass due to decreased osteoclast formation, accompanied by elevated osteoprotegerin/RANKL ratios in serum. Vagotomy in wild-type mice also significantly increased the serum osteoprotegerin/RANKL ratio, and elevated bone mass seen in nAchR7(-/-) mice was reversed in alpha7nAchR/osteoprotegerin-doubly-deficient mice. alpha7nAchR loss significantly increased TNFalpha expression in Mac1-positive macrophages, and TNFalpha increased the osteoprotegerin/RANKL ratio in osteoblasts. Targeting TNFalpha in nAchR7(-/-) mice normalized both serum osteoprotegerin/RANKL ratios and bone mass. Administration of nicotine, an alpha7nAchR ligand, to wild-type mice increased serum RANKL levels. Thus, vagal nerve stimulation of macrophages via alpha7nAchR regulates bone mass by modulating osteoclast formation." | alpha7 Nicotinic Acetylcholine Receptor |
Understanding microbial niche differentiation along ecological and geochemical gradients is critical for assessing the mechanisms of ecosystem response to hydrologic variation and other aspects of global change. The lineage-specific biogeochemical roles of the widespread phylum Acidobacteria in hydrologically sensitive ecosystems, such as peatlands, are poorly understood. Here, we demonstrate that Acidobacteria sublineages in Sphagnum peat respond differentially to redox fluctuations due to variable oxygen (O(2)) availability, a typical feature of hydrologic variation. Our genome-centric approach disentangles the mechanisms of niche differentiation between the Acidobacteria genera Holophaga and Terracidiphilus in response to the transient O(2) exposure of peat in laboratory incubations. Interlineage functional diversification explains the enrichment of the otherwise rare Holophaga in anoxic peat after transient O(2) exposure in comparison to Terracidiphilus dominance in continuously anoxic peat. The observed niche differentiation of the two lineages is linked to differences in their carbon degradation potential. Holophaga appear to be primarily reliant on carbohydrate oligomers and amino acids, produced during the prior period of O(2) exposure via the O(2)-stimulated breakdown of peat carbon, rich in complex aromatics and carbohydrate polymers. In contrast, Terracidiphilus genomes are enriched in diverse respiratory hydrogenases and carbohydrate active enzymes, enabling the degradation of complex plant polysaccharides into monomers and oligomers for fermentation. We also present the first evidence for the potential contribution of Acidobacteria in peat nitrogen fixation. In addition to canonical molybdenum-based diazotrophy, the Acidobacteria genomes harbor vanadium and iron-only alternative nitrogenases. Together, the results better inform the different functional roles of Acidobacteria in peat biogeochemistry under global change. IMPORTANCE Acidobacteria are among the most widespread and abundant members of the soil bacterial community, yet their ecophysiology remains largely underexplored. In acidic peat systems, Acidobacteria are thought to perform key biogeochemical functions, yet the mechanistic links between the phylogenetic and metabolic diversity within this phylum and peat carbon transformations remain unclear. Here, we employ genomic comparisons of Acidobacteria subgroups enriched in laboratory incubations of peat under variable O(2) availability to disentangle the lineage-specific functional roles of these microorganisms in peat carbon transformations. Our genome-centric approach reveals that the diversification of Acidobacteria subpopulations across transient O(2) exposure is linked to differences in their carbon substrate preferences. We also identify a previously unknown functional potential for biological nitrogen fixation in these organisms. This has important implications for carbon, nitrogen, and trace metal cycling in peat systems. | Acidobacteria |
Despite the prevalence of developmental myopathies resulting from muscle fiber defects, the earliest stages of myogenesis remain poorly understood. Unc45b is a molecular chaperone that mediates the folding of thick-filament myosin during sarcomere formation; however, Unc45b may also mediate specific functions of non-muscle myosins (NMMs). unc45b Mutants have specific defects in striated muscle development, which include myocyte detachment indicative of dysfunctional adhesion complex formation. Given the necessity for non-muscle myosin function in the formation of adhesion complexes and premyofibril templates, we tested the hypothesis that the unc45b mutant phenotype is not mediated solely by interaction with muscle myosin heavy chain (mMHC). We used the advantages of a transparent zebrafish embryo to determine the temporal and spatial patterns of expression for unc45b, non-muscle myosins and mMHC in developing somites. We also examined the formation of myocyte attachment complexes (costameres) in wild-type and unc45b mutant embryos. Our results demonstrate co-expression and co-regulation of Unc45b and NMM in myogenic tissue several hours before any muscle myosin heavy chain is expressed. We also note deficiencies in the localization of costamere components and NMM in unc45b mutants that is consistent with an NMM-mediated role for Unc45b during early myogenesis. This represents a novel role for Unc45b in the earliest stages of muscle development that is independent of muscle mMHC folding. | Costameres |
Co-precipitation was a novel method for improving the functional properties of pure proteins. To investigate the mechanism of this effect, different protein proportions of soy-wheat co-precipitated protein were extracted by isoelectric point co-precipitation. Soy protein isolate (SPI) was mainly linked to wheat protein (WP) through non-covalent forces and disulfide bonds as determined by circular dichroism spectroscopy, disulfide bond, protein fraction extraction, interaction, and molecular modeling. Amino acid analysis indicated that co-precipitation could increase wheat lysine content. Furthermore, co-precipitation improved multiple functional properties of pure protein, and the emulsifying and foaming properties of the composite system with a mass ratio of 7:3 outperformed those of other systems. At the same time, correlation analysis revealed that protein structure and intermolecular forces significantly affected its functional properties. This study provided some useful and interesting information for the development and application of protein-protein systems with diverse functional properties. | Soybean Proteins |
The conventional way of appreciating working capacity is no longer satisfying considering the improved diagnostic tools with increasing frequency of various deformities, instability and ankylosis and their combinations. As in the evaluation of peripheral joint function a concept is proposed, which is based on the structural changes in the motion segments. The concept is practicable in all parts of the vertebral column and allows a differentiated judgement within the usual percentages. | Disability Evaluation |
Recently, Sui and colleagues introduced an experimental task to investigate prioritization of arbitrary stimuli associated with the self. They demonstrated that after being told to associate three identities (self, friend, stranger) with three arbitrary stimuli (geometrical shapes), participants were faster in a perceptual matching task to recognise matching pairs of self-associated shape with self-label, than respective friend or stranger-related pairings. They interpreted this as evidence that a brief self-association is sufficient to facilitate processing of previously neutral stimuli. However, in the matching trials of the self-prioritization task, participants are processing not only self-associated arbitrary stimuli but also familiar verbal labels with an established meaning. Therefore, the self-advantage may be caused by familiarity of the labels, rather than self-association of the shapes. To test whether self-prioritization can be elicited in a task employing exclusively neutral stimuli, we asked participants to associate avatar faces with three identities (self, name of best friend, and stranger) and replaced labels with unfamiliar abstract symbols that were associated to the words (you, friend, stranger) before the actual experiment started. The results presented the usual pattern of self-prioritization showing that this effect does not critically depend on the presence of familiar labels and that it can be elicited in the absence of any familiar stimuli. | Pattern Recognition, Visual |
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