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Viola odorata L. (Violaceae), an Indian medicinal plant, contains a plethora of cyclotides, which are a class of cyclic peptides derived from plants, possessing several applications. Somatic embryo culture of V. odorata was developed, via indirect somatic embryogenesis, to serve as an alternative to natural plant biomass for sustainable and continuous production of its bioactive ingredients, such as cyclotides. Among the various combinations of phytohormones tested, Murashige and Skoog medium supplemented with 1â¯mg/l thidiazuron gave rise to the maximum frequency of induction (86.7%) and a high number of somatic embryos (3) from an embryogenic callus. Identification and characterization of cyclotides in the somatic embryos were carried out using a Fourier transform mass spectrometer coupled with liquid chromatography (LC-FTMS). Among the cyclotides identified in the study, few were found to be exclusively present in the somatic embryo culture. Furthermore, the relative abundance of the cyclotides was higher in somatic embryo extract than in the natural plant extract. The biological activities (cytotoxic, haemolytic and antimicrobial) of the somatic embryos and the parent plant were compared. Unlike the natural plants, the somatic embryo extracts demonstrated specificity i.e. they were found to be potent against cancerous cells but not against non-cancerous cell line or red blood cells. In contrast to the plant extract, the somatic embryos extracts were found to be potent against Escherichia coli and Staphylococcus aureus. These results suggest that somatic embryos of V. odorata (rich in cyclotides) can be used as an alternative to plant biomass for its therapeutic applications and germplasm conservation. | Violaceae |
A total of 305 patients with community-acquired pneumonia have participated in comparative or non-comparative studies involving cefetamet pivoxil. Of these, 211 (55 adults and 156 children) were involved in a series of open, prospective, comparator-controlled, multi-centre studies. Adults were randomized to receive either cefetamet pivoxil 1000 mg twice daily or amoxycillin 750 mg 3-times daily for 10 days. Children received either cefetamet pivoxil 10 mg/kg twice daily, cefetamet pivoxil 20 mg/kg twice daily or cefaclor 10 mg/kg 3-times daily for 7 to 8 days. The remaining 94 patients were treated openly with cefetamet pivoxil, with most patients receiving cefetamet pivoxil 500 mg twice daily for an average of 10 days; an elderly sub-group of these patients aged 70 to 103 years received therapy for an average of 11 days. The main causative organisms isolated were Streptococcus pneumoniae and Haemophilus influenzae. In adult patients, a successful clinical outcome was achieved in 100% of assessable patients receiving cefetamet pivoxil 1000 mg twice daily, and about 90% in those receiving 500 mg twice daily. The success rate in children was 98% for both dose levels of cefetamet pivoxil and 90% for those receiving cefaclor. In elderly patients, the percentage was 78% for the 500 mg twice daily patients. Thus, the standard dose of cefetamet pivoxil (500 mg twice daily in adults, 10 mg/kg twice daily in children) was well tolerated and proved to be at least as effective as the comparator drugs which were given 3-times a day. | Ceftizoxime |
The mitochondrial respiratory chain is a powerful source of reactive oxygen species, considered as the pathogenic agent of many diseases and of aging. We have investigated the role of Complex I in superoxide radical production in bovine heart submitochondrial particles and found, by combined use of specific inhibitors of Complex I and by Coenzyme Q (CoQ) extraction from the particles, that the one-electron donor in the Complex to oxygen is a redox center located prior to the binding sites of three different types of CoQ antagonists, to be identified with a Fe-S cluster, most probably N2 on the basis of several known properties of this cluster. Short chain CoQ analogs enhance superoxide formation, presumably by mediating electron transfer from N2 to oxygen. The clinically used CoQ analog, idebenone, is particularly effective in promoting superoxide formation. | Hydroxymercuribenzoates |
Bats have been demonstrated to be natural reservoirs of severe acute respiratory syndrome coronavirus (SARS CoV) and Middle East respiratory syndrome (MERS) CoV. Faecal samples from 248 individuals of 20 bat species were tested for partial RNA-dependent RNA polymerase gene of CoV and 57 faecal samples from eight bat species were tested positive. The highest detection rate of 44% for Scotophilus kuhlii, followed by 30% for Rhinolophus monoceros. Significantly higher detection rates of coronaviral RNA were found in female bats and Scotophilus kuhlii roosting in palm trees. Phylogenetic analysis classified the positive samples into SARS-related (SARSr) CoV, Scotophilus bat CoV 512 close to those from China and Philippines, and Miniopterus bat CoV 1A-related lineages. Coronaviral RNA was also detected in bat guano from Scotophilus kuhlii and Myotis formosus flavus on the ground and had potential risk for human exposure. Diverse bat CoV with zoonotic potential could be introduced by migratory bats and maintained in the endemic bat population in Taiwan." | Severe acute respiratory syndrome-related coronavirus |
BACKGROUND: Over the past several decades, changes in legislation and regulations have been implemented in oral health care in the Netherlands. In 1995, for example, a major transformation in the funding of oral health care was implemented, after which most oral health care for adults was no longer covered by national insurance. In 1997, the Individual Healthcare Professions Act, in which the authorizations of care providers were described, was established. The Healthcare Quality, Complaints and Disputes Act, established in 2016, concerns the accountability of professional behavior. Regulations concerning employment have changed several times since 1995. These changes have affected the work and practice situation of oral health care providers. METHODS: Data from many publicly available sources were gathered and combined with internal reports mainly derived from the Data Stations project of the Royal Dutch Dental Association. This project was established in 1995 and, since its initiation, 6716 dentists have participated an average of 6.7 times. RESULTS: Between 1995 and 2018, nearly all professional groups in oral health care increased, particularly those of dental hygienists and prevention assistants. The number of dental practices decreased, but practices got larger in terms of dental units, number of patients, and personnel. The percentage of inhabitants visiting oral health care professionals remained unchanged, but the type of care provided moved towards more prevention. Oral health care providers exploited new opportunities to enhance and express their professional behavior. CONCLUSIONS: Oral health care in the Netherlands has evolved in recent years toward more collaboration in teams, and professions have established institutions to promote the quality and safety of care. Greater emphasis has been placed on prevention of dental diseases. These processes were influenced by new legislation and regulations, demographic changes within professional groups, and other social developments. | Dental Health Services |
Despite the chronic and increasingly prevalent nature of actinic keratosis (AK) and existing evidence supporting assessment of the entire cancerization field during clinical management, a standardized definition of the AK field to aid in the understanding and characterization of the disease is lacking. The objective of this review was to present and appraise the available evidence describing the AK cancerization field, with the aim of determining a precise definition of the AK field in terms of its molecular (including genetic and immunological), histological and clinical characteristics. Eight European dermatologists collaborated to conduct a review and expert appraisal of articles detailing the characteristics of the AK field. Articles published in English before August 2016 were identified using PubMed and independently selected for further assessment according to predefined preliminary inclusion and exclusion criteria. In addition, a retrospective audit of patients with AK was performed to define the AK field in clinical terms. A total of 32 review articles and 47 original research articles provided evidence of sun-induced molecular (including genetic and immunological) and histological skin changes in the sun-exposed area affected by AK. However, the available literature was deemed insufficient to inform a clinical definition of the AK field. During the retrospective audit, visible signs of sun damage in 40 patients with AK were assessed. Telangiectasia, atrophy and pigmentation disorders emerged as 'reliable or very reliable' indicators of AK field based on expert opinion, whereas 'sand paper' was deemed a 'moderately reliable' indicator. This literature review has revealed a significant gap of evidence to inform a clinical definition of the AK field. Therefore, the authors instead propose a clinical definition of field cancerization based on the identification of visible signs of sun damage that are reliable indicators of field cancerization based on expert opinion. | Keratosis, Actinic |
Three total protein assays were analyzed to determine the extent of deviation encountered when a constant measured reagent blank is compared to a continuously decreasing true reagent blank. This blank effect owes its regressive nature to the consumption of the active reagent ingredient by the protein reactive species, variably and sometimes, with certain reactants, nonlinearly in the presence of increasing protein concentrations. However, the blank effect of interest here is apparent only when the reagent and the reagent-protein complex present overlapping spectra and therefore absorb at the wavelength of measurement. Thus it was found that while the biuret and the Coomassie brilliant blue assays produced pronounced differences in the variable true reagent blanks, the Folin-Ciocalteau reaction did not develop a deviation from the true blank since the reagent blank does not absorb to any extent at the assay wavelength. In this manner, the latter procedure could serve as a marker against which the former two blank reactions can be shown to display relatively excessive deviations. | Biuret Reaction |
Colorado tick fever virus is transmitted by Dermacentor andersoni ticks. In Canada, these ticks are found in the southern regions of British Columbia (Rocky Mountains) and Alberta, as well as southwestern Saskatchewan. Colorado tick fever should be clinically suspected in patients presenting with a biphasic febrile illness and leukopenia following tick exposure in the appropriate geographic area. | Coltivirus |
Gustatory sweating of the external auditory canal is extremely rare. A clinical case, that is only the second in the English literature, is presented. The potential pathogenesis and its treatment options are discussed. | Sweating, Gustatory |
Glycation is a nonenzymatic posttranslational modification (PTM) known to be increased in the brains of hyperglycemic patients. Alpha-synuclein (alphaSN), a central player in the etiology of Parkinson's disease, can be glycated at lysine residues, thereby reducing alphaSN fibril formation in vitro and modulating alphaSN aggregation in cells. However, the molecular basis for these effects is unclear. To elucidate this, we investigated the aggregation of alphaSN modified by eight glycating agents, namely the dicarbonyl compound methylglyoxal (MGO) and the sugars ribose, fructose, mannose, glucose, galactose, sucrose, and lactose. We found that MGO and ribose modify alphaSN to the greatest extent, and these glycation products are the most efficient inhibitors of fibril formation. We show glycation primarily inhibits elongation rather than nucleation of alphaSN and has only a modest effect on the level of oligomerization. Furthermore, glycated alphaSN is not significantly incorporated into fibrils. For both MGO and ribose, we discovered that a level of approximately 5 modifications per alphaSN is optimal for inhibition of elongation. The remaining sugars showed a weak but optimal inhibition at approximately 2 modifications per alphaSN. We propose that this optimal level balances the affinity for the growing ends of the fibril (which decreases with the extent of modification) with the ability to block incorporation of subsequent alphaSN subunits (which increases with modification). Our results are not only relevant for other alphaSN PTMs but also for understanding PTMs affecting other fibrillogenic proteins and may thus open novel avenues for therapeutic intervention in protein aggregation disorders. | Pyruvaldehyde |
We studied the epidemiology of antibiotic resistance and adherence properties among all Hafnia alvei clinical isolates collected from August 2003 to February 2005 from patients hospitalized in the hospital of Orleans, France. The isolates were typed by random amplified polymorphic DNA (RAPD), screened for antibiotic resistance and bacterial adherence to A549 respiratory and T24 bladder cells. Six intestinal, 3 respiratory, and 8 isolates from different body sites were collected. A total of 12 RAPD profiles were found, demonstrating a high genetic diversity. All the isolates were resistant to amoxicillin + clavulanate and cephalothin and sensitive to aminoglycosides, fluoroquinolones, cefepime and imipenem. Six isolates had a high-level and constitutive cephalosporinase production phenotype. Three independent isolates were resistant or had intermediate sensitivity to nalidixic acid, sulfonamide and trimethoprim or chloramphenicol. All the isolates adhered efficiently to the two cell lines with a higher effectiveness of adherence to bladder cells. The respiratory isolates adhered more efficiently to epithelial cells than intestinal isolates. No relationship was found between antibiotic resistance phenotypes, adherence properties, and RAPD types. In conclusion, H. alvei is an unusual nosocomial pathogen with little acquired antibiotic resistance able to adhere to human epithelial cells from different human body compartments. | Hafnia alvei |
Plasmodium vivax and P. falciparum, the parasites responsible for most human malaria worldwide, exhibit striking biological differences, which have important clinical consequences. Unfortunately, P. vivax, unlike P. falciparum, cannot be cultivated continuously in vitro, which limits our understanding of its biology and, consequently, our ability to effectively control vivax malaria. Here, we describe single-cell gene expression profiles of 9,215 P. vivax parasites from bloodstream infections of Aotus and Saimiri monkeys. Our results show that transcription of most P. vivax genes occurs during short periods of the intraerythrocytic cycle and that this pattern of gene expression is conserved in other Plasmodium species. However, we also identify a strikingly high proportion of species-specific transcripts in late schizonts, possibly associated with the specificity of erythrocyte invasion. Our findings provide new and robust markers of blood-stage parasites, including some that are specific to the elusive P. vivax male gametocytes, and will be useful for analyzing gene expression data from laboratory and field samples. | Schizonts |
Purinergic receptor is a potential drug target for neuropathic pain, Alzheimer disease, and prostate cancer. Focusing on the structure-based ligand discovery, docking analysis on the crystal structure of P2Y(1) receptor (P2Y(1)R) with 923 derivatives of 1-indolinoalkyl 2-phenolic compound is performed to understand the molecular insights of the receptor. The structural model identified the top novel ligands, 426 (compound 1) and 636 (compound 2) having highest binding affinity with the docking score of -7.38 and -6.92. We have reported the interaction efficacy and the dynamics of P2Y(1)R protein with the ligands. The best hits synthesized were experimentally optimized as a potent P2Y(1) agonists. These ligands exhibits anti-proliferative effect against the PC-3 and DU-145 cells (IC(50) = 15 microM - 33 microM) with significant increase in the calcium level in dose- and time-dependent manner. Moreover, the activation of P2Y(1)R induced the apoptosis via Capase3/7 and ROS signaling pathway. Thus it is evidenced that the newly synthesized ligands, as a P2Y(1)R agonists could potentially act as a therapeutic drug for treating prostate cancer." | Purinergic P2 Receptor Agonists |
CLINICAL RELEVANCE: The discovery of an accommodative response to ocular surface stimulation could inform clinicians and patients that optical effects may occur due to ocular discomfort and perhaps an assessment of the accommodative system after carrying out interventions impacting the ocular surface, may be warranted. BACKGROUND: There have been no previous reports evaluating the effect of noxious stimulation on accommodation. Here, the accommodative response of healthy participants after the application of noxious corneal stimulation is characterised. METHODS: A computerised Belmonte pneumatic esthesiometer was used to determine detection thresholds (using ascending method of limits), and to randomly deliver mechanical and chemical stimuli from levels of detection threshold to twice the threshold in 50% steps, to the central cornea of 15 healthy subjects. For each suprathreshold stimulus, accommodative and pupil responses were measured with a validated eccentric infrared photorefractor. Quantitative differences in accommodative/pupil response, stimulus modality/intensity and left/right eye were analysed using repeated measures ANOVA. Tukey HSD tests were used for all post hoc analyses. RESULTS: Accommodation increased from baseline as the corneal apical stimulus intensity increased. This happened regardless of whether mechanical or chemical stimulation occurred (ANOVA, p < 0.05). At 200% threshold, accommodative response was greater than all stimulus intensities (Tukey HSD, all p < 0.05). There was no difference in pupil response between the stimulation intensities (100%, 150% and 200% threshold). There was no difference in accommodative response between the left and right eye for mechanical (ANOVA, p > 0.05) and chemical stimulation (ANOVA, p > 0.05). CONCLUSION: Noxious stimulation of the cornea seems to produce a dose-dependent increase in the accommodative response in the eyes but not a dose-dependent pupil response. | Stimulation, Chemical |
Osteopenia, rickets, and fractures from nutrient deficiencies can occur during infancy, particularly in preterm infants. Bone mass accretion during the first year of life is equal to or greater than that achieved at any other stage of life, including adolescence. Optimizing calcium and bone status during infancy can have immediate benefits in maintaining calcium homeostasis and preventing disturbances in bone mineralization and can provide long-term benefits by helping infants to later reach their maximum genetic potential for peak bone mass, a prerequisite for the prevention of osteoporosis and its complications. Dietary calcium requirements during infancy generally reflect the need to achieve normal growth and bone mineralization because 99 percent of total body calcium is present in the skeleton. Knowledge of physiologic factors that determine infant calcium requirements and the bioavailability of calcium from various dietary sources is important to ensuring bone health during infancy. Also key are the practical issues related to optimizing calcium nutriture in infants born at term and prematurely. | Decalcification, Pathologic |
The purposes of this study were to examine prevalence of fear of falling (FOF) and decreased balance confidence in individuals with postpolio syndrome (PPS) and to determine whether balance confidence was correlated with health-related quality of life (HRQOL) in this population. A survey, which included demographic questions, the Activities-specific Balance Confidence (ABC) Scale, and the MOS SF-36v2, was made available by mail and electronically to individuals with PPS. Descriptive and correlation statistics were used to analyze the responses. Fear of falling was reported in 95% of respondents, with 80% indicating that FOF affected their quality of life. Median ABC score (42 of 100), physical component score (27 of 100), and mental component score (47 of 100) were below average compared with the general population. A moderate correlation (r = 0.4; p < 0.001) was found between balance confidence and the physical component score of HRQOL in PPS. There was an overwhelming presence of FOF and severely impaired balance confidence in the majority of those with PPS. A fair correlation between the physical functioning component of HRQOL and balance confidence was noted in this population. | Postpoliomyelitis Syndrome |
Ultrasound guidance is used increasingly to perform the following 6 bedside procedures that are core competencies of hospitalists: abdominal paracentesis, arterial catheter placement, arthrocentesis, central venous catheter placement, lumbar puncture, and thoracentesis. Yet most hospitalists have not been certified to perform these procedures, whether using ultrasound guidance or not, by specialty boards or other institutions extramural to their own hospitals. Instead, hospital privileging committees often ask hospitalist group leaders to make ad hoc intramural certification assessments as part of credentialing. Given variation in training and experience, such assessments are not straightforward sign offs." We thus convened a panel of experts to conduct a systematic review to provide recommendations for credentialing hospitalist physicians in ultrasound guidance of these 6 bedside procedures. Pathways for initial and ongoing credentialing are proposed. A guiding principle of both is that certification assessments for basic competence are best made through direct observation of performance on actual patients." | Thoracentesis |
In this study, the toxic effects of verapamil (VRP) were studied on juvenile rainbow trout, Oncorhynchus mykiss, by chronic semi-static bioassay. Fish were exposed to sublethal concentrations of VRP (0.5, 27 and 270 mug/L) for 0, 21 and 42 d. Multiple biomarkers were measured, including morphological indices, hematological parameters and antioxidant responses of different tissues (brain, gill, liver, muscle and intestine). Based on the results, there was no significant change in all parameters measured in fish exposed to VRP at environmental related concentration, but VRP-induced stress in fish exposed to higher concentrations reflected the significant changes of physiological and biochemical responses. Through principal component analysis and integrated biomarker response assessment, effects induced by VRP-stress in each test group were distinguished. Additionally, all parameters measured in this study displayed various dependent patterns to VRP concentrations and exposure time using two-way ANOVA statistic analysis. In short, the multiple responses in fish indicated that VRP induced physiological stress and could be used as potential biomarkers for monitoring residual VRP in aquatic environment; but molecular and genetic mechanisms of these physiological responses in fish are not clear and need to be further studied. | Oncorhynchus |
BACKGROUND: Nano-sized complexes of calcium phosphate mineral and proteins (calcifying nanoparticles [CNPs]) serve as mineral chaperones. Thus, CNPs may be both a result and cause of soft tissue calcification processes. This study determined if CNPs could augment calcification of arterial vascular smooth muscle cells in vitro. METHODS: CNPs 210 nm in diameter were propagated in vitro from human serum. Porcine aortic smooth muscle cells were cultured for up to 28 days in medium in the absence (control) or presence of 2 mM phosphate ([P] positive calcification control) or after a single 3-day exposure to CNPs. Transmission electron-microscopy was used to characterize CNPs and to examine their cellular uptake. Calcium deposits were visualized by light microscopy and von Kossa staining and were quantified by colorimetry. Cell viability was quantified by confocal microscopy of live-/dead-stained cells and apoptosis was examined concurrently by fluorescent labeling of exposed phosphatidylserine. RESULTS: CNPs, as well as smaller calcium crystals, were observed by transmission electron-microscopy on day 3 in CNP-treated but not P-treated cells. By day 28, calcium deposits were visible in similar amounts within multicellular nodules of both CNP- and P-treated cells. Apoptosis increased with cell density under all treatments. CNP treatment augmented the density of apoptotic bodies and cellular debris in association with mineralized multicellular nodules. CONCLUSION: Exogenous CNPs are taken up by aortic smooth muscle cells in vitro and potentiate accumulation of smooth-muscle-derived apoptotic bodies at sites of mineralization. Thus, CNPs may accelerate vascular calcification. | Calcifying Nanoparticles |
Alkali therapy for certain organic acidoses remains a topic of ongoing controversy, but little attention has been given to a related medical controversy, namely the prescription of alkali for respiratory acidosis. We first describe the determinants of carbon dioxide retention in the 2 types of respiratory failure; hypercapnic respiratory failure and hypoxemic respiratory failure with coexisting hypercapnia. We then highlight the deleterious consequences of severe acidemia for several organ systems, particularly the cardiovascular and central nervous systems. We argue that alkali therapy is not indicated for respiratory acidosis as a simple acid-base disturbance. Notwithstanding, we recommend prescription of alkali for severe acidemia caused by mixed acidosis (ie, combined respiratory and metabolic acidosis) or permissive hypercapnia. We examine the utility of alkali therapy in various clinical scenarios incorporating respiratory acidosis. We conclude that controlled studies will be required to test the impact of alkali therapy on clinical outcomes of these clinical settings. Such studies should also examine the optimal mode of administering alkali (amount, rate, and tonicity) and the blood pH to be targeted. The development of new buffers should be explored, especially systems that do not generate carbon dioxide or even consume it. | Acidosis, Respiratory |
Multiprotein complexes (MPCs) play crucial roles in cell signaling. Two kinds of MPCs can be distinguished: (i) Constitutive, abundant MPCs--for example, multisubunit receptors or transcription factors; and (ii) signal-induced, transient, low copy number MPCs--for example, complexes that form upon binding of Src-homology 2 (SH2) domain-containing proteins to tyrosine-phosphorylated proteins. Blue native polyacrylamide gel electrophoresis (BN-PAGE) is a separation method with a higher resolution than gel filtration or sucrose density ultracentrifugation that can be used to analyze abundant, stable MPCs from 10 kD to 10 MD. In contrast to immunoprecipitation and two-hybrid approaches, it allows the determination of the size, the relative abundance, and the subunit composition of an MPC. In addition, it shows how many different complexes exist that share a common subunit, whether free monomeric forms of individual subunits exist, and whether these parameters change upon cell stimulation. Here, we give a detailed protocol for the separation of MPCs from total cellular lysates or of prepurified MPCs by one-dimensional BN-PAGE or by two-dimensional BN-PAGE and SDS-PAGE. | Multiprotein Complexes |
The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals." | Influenza A Virus, H1N2 Subtype |
Streptococcus gordonii OMZ1039, isolated from supragingival dental plaque, was found to harbour a prophage, PH15, whose excision could be induced by mitomycin treatment. Phage PH15 belongs to the Siphoviridae. The complete genome sequence of PH15 was determined. The genome was 39 136 bp in size and contained 61 ORFs. The genome of PH15 was most similar in the structural module to the temperate bacteriophages MM1 and phiNIH1.1 from Streptococcus pneumoniae and Streptococcus pyogenes, respectively. In strain OMZ1039, PH15 was found to reside as a prophage in the cysteinyl-tRNA gene. A plasmid, harbouring the attP site and the integrase gene downstream of a constitutive promoter, was capable of site-specific integration into the genomes of different oral streptococcal species. The phage endolysin was purified after expression in Escherichia coli and found to inhibit growth of all S. gordonii strains tested and several different streptococcal species, including the pathogens Streptococcus mutans, S. pyogenes and Streptococcus agalactiae. | Streptococcus gordonii |
Many biologically important cell binding processes, such as the rolling of leukocytes in the vasculature, are multivalent, being mediated by large numbers of weak binding ligands. Quantitative agreement between experiments and models of rolling has been elusive and often limited by the poor understanding of the binding and unbinding kinetics of the ligands involved. Here, we present a cell-free experimental model for such rolling, consisting of polymer microspheres whose adhesion to a glass surface is mediated by ligands with well-understood force-dependent binding free energy-short complementary DNA strands. We observe robust rolling activity for certain values of the shear rate and the grafted DNA strands' binding free energy and force sensitivity. The simulation framework developed to model leukocyte rolling, adhesive dynamics, quantitatively captures the mean rolling velocity and lateral diffusivity of the experimental particles using known values of the experimental parameters. Moreover, our model captures the velocity variations seen within the trajectories of single particles. Particle-to-particle variations can be attributed to small, plausible differences in particle characteristics. Overall, our findings confirm that state-of-the-art adhesive dynamics simulations are able to capture the complex physics of particle rolling, boding well for their extension to modeling more complex systems of rolling cells. | Microspheres |
The endoplasmic reticulum (ER) is not only important for protein synthesis and folding but is also crucial for lipid synthesis and metabolism. In the current study, we demonstrate an important role of ceramide synthases (CerS) in ER stress and NAFLD progression. Ceramide is important in sphingolipid metabolism, and its acyl chain length is determined by a family of six CerS in mammals. CerS2 generates C22-C24 ceramides, and CerS5 or CerS6 produces C16 ceramide. To gain insight into the role of CerS in NAFLD, we used a high-fat diet (HFD)-induced NAFLD mouse model. Decreased levels of CerS2 and increased levels of CerS6 were observed in the steatotic livers of mice fed a HFD. In vitro experiments with Hep3B cells indicated the protective role of CerS2 and the detrimental role of CerS6 in the ER stress response induced by palmitate treatment. In particular, CerS6 overexpression increased sterol regulatory element-binding protein-1 (SREBP-1) cleavage with decreased levels of INSIG-1, leading to increased lipogenesis. Blocking ER stress abrogated the detrimental effects of CerS6 on palmitate-induced SREBP-1 cleavage. In accordance with the protective role of CerS2 in the palmitate-induced ER stress response, CerS2 knockdown enhanced ER stress and SREBP-1 cleavage, and CerS2 heterozygote livers exhibited a stronger ER stress response and higher triglyceride levels following HFD. Finally, treatment with a low dose of bortezomib increased hepatic CerS2 expression and protected the development of NAFLD following HFD. These results indicate that CerS and its derivatives impact hepatic ER stress and lipogenesis differently and might be therapeutic targets for NAFLD. | Sphingosine N-Acyltransferase |
Phytanic acid is a branched-chain fatty acid that accumulates in a variety of metabolic disorders. High levels of phytanic acid found in patients can exceed the millimolar range and lead to severe symptoms. Degradation of phytanic acid takes place by alpha-oxidation inside the peroxisome. A deficiency of its breakdown, leading to elevated levels, can result from either a general peroxisomal dysfunction or from a defect in one of the enzymes involved in alpha-oxidation. Research on Refsum disease, belonging to the latter group of disorders and characterized by a deficiency of the first enzyme of alpha-oxidation, has extended our knowledge of phytanic acid metabolism and pathology of the disease greatly over the past few decades. This review will centre on this research on phytanic acid: its origin, the mechanism by which its alpha-oxidation takes place, its role in human disease and the way it is produced from phytol." | Chondrodysplasia Punctata, Rhizomelic |
In a planar, superconducting magnetic resonance imaging (MRI) system, the gradient assembly is placed into the groove of the SC magnet. Conventional gradient coil design method considers the shielding of pole face only, but neglects the surrounding metal structures at the coil side, thus leading to large stray field leakage and resulting in serious eddy current artefact. A novel coil shielding method was proposed in this work by a full consideration of the stray fields on the pole face and also the coil ends. The gradient coil design exemplification of a 0.7T planar superconducting MRI system was presented. In the new design, the maximum stray field at the surface of the ambient structure was reduced more than six times for the transverse coils and around four times for the longitudinal coil. The highly shielded gradient coil also produced linear gradient fields (<5%) over the imaging volume. | Superconductivity |
There is increasing interest in rearing modified mosquitoes for mass release to control vector-borne diseases, particularly Wolbachia-infected Aedes aegypti for suppression of dengue. Successful introductions require release of high quality mosquitoes into natural populations. Potential indicators of quality are body size and shape. We tested to determine if size, wing/thorax ratio, and wing shape are associated with field fitness of Wolbachia-infected Ae. aegypti. Compared with field-collected mosquitoes, released mosquitoes were larger in size, with lower size variance and different wing shape but similar in wing-thorax ratio and its associated variance. These differences were largely attributed to nutrition and to a minor extent to wMel Wolbachia infection. Survival potential of released female mosquitoes was similar to those from the field. Females at oviposition sites tended to be larger than those randomly collected from BG-Sentinel traps. Rearing conditions should thus aim for large size without affecting wing/thorax ratios. | Aedes |
OBJECT: Pure sylvian fissure arteriovenous malformations (AVMs) are vascular malformations confined to the sylvian fissure without parenchymal involvement. Because the branches of the middle cerebral artery are arteries of passage and the margins between the AVM and the insula cortex may be ill defined, many surgeons regard pure sylvian fissure AVMs as inoperable. The authors reviewed their surgical experience with eight patients harboring pure sylvian fissure AVMs to determine the incidence of operative morbidity. METHODS: All eight patients experienced seizures, five (63%) had headaches, and three (38%) experienced hemorrhages. Preoperatively, six patients (75%) were normal neurologically and two (25%) had neurological deficits. Five (63%) of eight sylvian fissure AVMs were located in the dominant hemisphere. The size of the nidus ranged from 6 to 27 cm3 (mean 14 cm3). Complete removal of the AVM was documented by postoperative angiography in every case. Seizures were reduced or eliminated and headaches were relieved in all affected patients. Transient neurological deficits, which included aphasia, short-term memory loss, and hemiparesis, occurred in four patients (50%). Within 3 months, all patients were functioning independently with no new neurological deficits. The status of two patients who had had preoperative neurological deficits improved postoperatively. Neuropsychological testing showed no new cognitive deficits. CONCLUSIONS: With appreciation for transient instances of postoperative morbidity, the outcome was excellent in all patients. The authors thus advocate microsurgery as the primary treatment for pure sylvian fissure AVMs. | Cerebral Aqueduct |
p53 is a central integrator of a plethora of signals and outputs these signals in the form of tumor suppression. It is well accepted that ubiquitination plays a major part in p53 regulation. Nonetheless, the molecular mechanisms by which p53 activity is controlled by ubiquitination are complex. Mdm2, a RING oncoprotein, was once thought to be the sole E3 ubiquitin ligase for p53, however recent studies have shown that p53 is stabilized but still degraded in the cells of Mdm2-null mice. Although the essential role of Mdm2 in p53 regulation is well established, there are an increasing number of other E3 ligases implicated in Mdm2-independent regulation of p53 by ubiquitination. The different types of ubiquitination on p53 by various E3 ligases have been linked to its differential effects on p53-mediated stress responses. In addition to proteasome-mediated degradation, ubiquitination of p53 acts as signals for degradation-independent functions, such as nuclear export. The function of ubiquitinated p53 varies in the nucleus and cytosol underlying the many potential contributions ubiquitinated p53 may have in promoting cell proliferation or death. Thus, p53 requires multiple layers of regulatory control to ensure correct temporal and spatial functions." | Ubiquitin-Specific Peptidase 7 |
OBJECTIVE: To discuss areas of differing opinion in the management of feline urethral obstruction and present current evidence to either support or refute common practices. ETIOLOGY: Urethral obstruction may occur as a result from a functional obstruction (idiopathic obstruction) or a physical obstruction, such as mucous plugs or calculi within the urethra. Potential risk factors for obstruction in cats include predominantly indoor status, decreased water intake, and increased body weight. DIAGNOSIS: The diagnosis is most commonly made based on history and initial physical exam-straining to urinate, vocalizing, signs of systemic illness, moderate to large firm bladder on abdominal palpation. THERAPY: Treatment is based on available evidence. The type of IV isotonic crystalloid used does not seem to matter and rate should be determined by need for fluid resuscitation, and replacement of deficit and ongoing losses. Though controversial, cystocentesis appears to be safe and may offer some benefits in initial management. There is evidence to suggest a smaller urethral catheter (3.5 Fr) may be associated with decreased risk of reobstruction. Routine use of antimicrobial agents in hospital is not recommended; they should be dispensed based on culture performed at the time of catheter removal. Though commonly used, evidence in support of antispasmodics is limited and further prospective investigation is needed. PROGNOSIS: Feline urethral obstruction is associated with 90-95% survival, with reported recurrence rates of 15-40%. Potential factors affecting recurrence include size or duration of indwelling urinary catheter, use of antispasmodic agents, patient age, and indoor-outdoor lifestyle; however, different studies offer conflicting results. Increased water intake and environmental modification do seem to decrease risk of recurrence. | Urethral Obstruction |
Although primary syphilis generally involves the genitalia, literature reports that 12% of chancres are extragenital, with the anus and oral cavity as the most frequent locations. We present hereby a case series of four chancres of the finger observed at the sexually transmitted infection centre of Milan between 2010 and 2021. | Syphilis |
BACKGROUND: Rheumatoid arthritis is a systemic autoimmune disease, considered the most common inflammatory articular disease among the general population. However, not only the joints are affected; rheumatoid arthritis also has an extra-articular manifestation. As for many other chronic diseases, rheumatoid arthritis may be exacerbated by poorer lifestyle choices. In fact, recent studies emphasize the role of nutrition and physical activity in this disease. AIM: In the current paper, we aim to describe lifestyle modifications based on diet and physical activity and other recommendations that seem to improve the clinical management and the disease outcome of Rheumatoid arthritis. RESULTS: A three-component lifestyle modification programme has been considered based on: (i) A low-fat low-sodium Mediterranean diet rich in fruits, vegetables, whole grains and nuts and poor in sugar-sweetened beverages, red and processed meat and trans fats, and the supplementation with omega-3 fatty acids, non-essential amino acids and probiotics, (ii) An appropriate physical activity programme based on an active daily lifestyle, aerobic exercise and resistance training and (iii) Adequate sleep hygiene and smoking reduction/cessation, that seems to have positive effects in terms of disease progression and related outcomes. CONCLUSION: Lifestyle modification programme should be considered as the basis of any treatment, (i.e., pharmacological treatment), in patients with rheumatoid arthritis. | Diet, Mediterranean |
The ageing of the population will increasingly result in reliance on the family for care in the community. Existing reviews have provided insights into the needs and health outcomes of family caregivers, but are disproportionately skewed towards spousal caregivers. Presently, a large majority of family caregivers are adult children. Adult children are distinct from spousal caregivers in terms of the combination of roles they occupy and the relationship they have with the care recipient. These unique considerations can have important implications for their well-being. A growing body of literature has investigated the factors that contribute to adult children caregivers' (ACCs) well-being; however, no reviews to date have synthesised this body of literature or appraised its methodological quality. Our objective was to identify the range and types of factors that contribute to ACC well-being across studies. A scoping review was conducted. Medline, Psycinfo, EMBASE and CINAHL databases (January 1996-August, 2012) were systematically searched for studies investigating ACC well-being. Inclusion/exclusion criteria were applied, methodological quality was appraised, the data were charted and a narrative synthesis was conducted. Fifty-five studies met our inclusion criteria. Factors that contribute to ACC well-being were found to be either: (i) care recipient-related (e.g. nature of limitations, amount of care required); (ii) caregiver-related (e.g. psychological dispositions of the ACC); or (iii) socially embedded (e.g. parent-child relationship, multiple role involvement, social support available to the ACC). Socially embedded factors that contribute to ACC well-being have received the most attention in the literature. Among these factors, ACC well-being is uniquely impacted by the quality of the parent-child relationship and combination of roles occupied. The majority of studies were cross-sectional. Future studies should therefore employ a longitudinal design to inform our understanding of the changes that take place in the parent-child relationship and multiple role involvement across the care-giving trajectory. | Adult Children |
The oral LD50 of a compound in hens does not reliably predict the neurotoxic dose of that compound. The oral LD50 in rats does not predict either the oral LD50 in hens or the neurotoxic dose in hens, so there is no justification for using the rat value to predict the neurotoxic dosage in hens. A strategy is presented for a stepwise approach to neurotoxicity testing in hens. | Leptophos |
A urinary excretion bioavailability study was conducted in 12 healthy male subjects to evaluate three 250-mg and three 500-mg chlorothiazide tablet products. The study was a crossover design, and urine samples were collected 1, 2, 3, 4, 6, 8, 12, and 24 hr after administration of each dose. The resulting data were statistically analyzed for significant differences in cumulative percent of dose excreted at each sampling time, total drug recovery after 24 hr, maximum excretion rate, and time of maximum excretion rate. No statistically significant differences were found between the three 250-mg tablets tested. The urinary drug recovery after administration of one of the 500-mg products was significantly (p less than 0.05) lower than that from the other two 500-mg tablets. The total mean recovery from each product ranged from only 11 to 20%, indicating that in general chlorothiazide was not well absorbed following oral administration. Attempts at correlating the urinary excretion data with the dissolution rate determinations were not successful. | Chlorothiazide |
Increased cardiovascular morbidity and mortality in patients with type 2 diabetes is well established; diabetes is associated with at least a 2-fold increased risk of coronary heart disease. Approximately two-thirds of deaths among persons with diabetes are related to cardiovascular disease. Previously, diabetes was regarded as a coronary risk equivalent," implying a high 10-year cardiovascular risk for every diabetes patient. Following the original study by Haffner et al., multiple studies from different cohorts provided varying conclusions on the validity of the concept of coronary risk equivalency in patients with diabetes. New guidelines have started to acknowledge the heterogeneity in risk and include different treatment recommendations for diabetic patients without other risk factors who are considered to be at lower risk. Furthermore, guidelines have suggested that further risk stratification in patients with diabetes is warranted before universal treatment. The Imaging Council of the American College of Cardiology systematically reviewed all modalities commonly used for risk stratification in persons with diabetes mellitus and summarized the data and recommendations. This document reviews the evidence regarding the use of noninvasive testing to stratify asymptomatic patients with diabetes with regard to coronary heart disease risk and develops an algorithm for screening based on available data." | Diabetes Complications |
The (pro)renin receptor (P)RR is a receptor for renin and prorenin, not only allowing local production of angiotensin I from angiotensinogen, but also inducing intracellular signaling. Intriguingly, (P)RR is also called ATP6AP2 because a (P)RR fragment was demonstrated to be associated with vacuolar-type H+-ATPase (V-ATPase), which is of importance for the maintenance of intracellular pH. Recent studies implicate that deletion of (P)RR results in the dysfunction of V-ATPase, suggesting that the (P)RR is essential for its role as a proton pump. Furthermore, the novel function of (P)RR as an adaptor protein between the Wnt receptor complex and the V-ATPase was discovered. Thus, (P)RR is a multi-functional molecule with functions beyond renin and prorenin. This review focuses on the current knowledge and issues of (P)RR and V-ATPase." | Phosphotransferases (Phosphate Group Acceptor) |
Lymphotoxin-beta (LTbeta) is a key regulator of immune system development, but also affects late stages in hair development. In addition, high expression of LTbeta at an early stage in epidermis hinted at a further function in hair follicle induction or epithelial development. We report that hair follicles were normally induced in LTbeta(-/-) skin, but the periderm detached from the epidermis earlier, accompanied by premature appearance of keratohyalin granules. Expression profiling revealed dramatic down-regulation of a gene cluster encoding periderm-specific keratin-associated protein 13 and four novel paralogs in LTbeta(-/-) skin prior to periderm detachment. Epidermal differentiation markers, including small proline-rich proteins, filaggrins and several keratins, were also affected, but transiently in LTbeta(-/-) skin at the time of abnormal periderm detachment. As expected, Tabby mice, which lack the EDA gene, the putative upstream regulator of LTbeta in skin, showed similar though milder periderm histopathology and alterations in gene expression. Overall, LTbeta shows a primary early function in periderm differentiation, with later transient effects on epidermal and hair follicle differentiation. | Lymphotoxin-beta |
An excessive neutrophil count is recognized as a valuable predictor of inflammation and is associated with a higher risk of adverse cardiac events in patients with heart failure. Our understanding of the effectors used by neutrophils to inflict proinflammatory actions needs to be advanced. Recently, emerging evidence has demonstrated a causative role of neutrophil-derived alarmins (i.e. S100A8/A9) in aggravating cardiac injuries by induction of inflammation. In parallel with the neutrophil count, high circulating levels of S100A8/A9 proteins powerfully predict mortality in patients with heart failure. As such, a deeper understanding of the biological functions of neutrophil-derived S100A8/A9 proteins would offer novel therapeutic insights. Here, the basic biology of S100A8/A9 proteins and their pleiotropic roles in cardiovascular diseases are discussed, focusing on heart failure. We also consider the evidence that therapeutic targeting of S100A8/A9 proteins by the humanized vaccine, antibodies or inhibitors is able to town down inflammatory injuries. | Alarmins |
Using the Nigerian Demographic and Health Survey (NDHS) of 2013, this study applies the social structure (feminist) and social learning perspective in understanding the severity of physical intimate partner violence (IPV) in Nigeria. About 26,403 married women were analyzed from the 2013 NDHS data. Multinomial regression was used to analyze variables that capture the social structural and social learning perspectives in relation to women's experience of minor and severe physical IPV. The study revealed that primary and secondary educational attainment, and being employed predicted severe physical IPV victimization. Alcohol consumption by the respondents' spouses, being a victim of childhood abuse, and witnessing IPV between parents predicted severe physical IPV. The finding of this study implies that experiences of IPV take place within a sociocultural context that shapes the social realities of the average Nigerian woman. | Social Learning |
All cell membranes are packed with proteins. The ability to investigate the regulatory mechanisms of protein channels in experimental conditions mimicking their congested native environment is crucial for understanding the environmental physicochemical cues that may fundamentally contribute to their functionality in natural membranes. Here we report on investigations of the voltage-induced gating of lysenin channels in congested conditions experimentally achieved by increasing the number of channels inserted into planar lipid membranes. Typical electrophysiology measurements reveal congestion-induced changes to the voltage-induced gating, manifested as a significant reduction of the response to external voltage stimuli. Furthermore, we demonstrate a similar diminished voltage sensitivity for smaller populations of channels by reducing the amount of sphingomyelin in the membrane. Given lysenin's preference for targeting lipid rafts, this result indicates the potential role of the heterogeneous organization of the membrane in modulating channel functionality. Our work indicates that local congestion within membranes may alter the energy landscape and the kinetics of conformational changes of lysenin channels in response to voltage stimuli. This level of understanding may be extended to better characterize the role of the specific membrane environment in modulating the biological functionality of protein channels in health and disease. | Membrane Microdomains |
Driven by the need to address integrated dental care, many UK dental schools have recognised the advantages of teaching dental practice, or dental primary care (DPC), as a separate and defined subject area. In such schools, DPC may be taught alongside specialist subjects such as restorative dentistry, oral surgery, oral medicine and those traditionally forming elements of the dental undergraduate curriculum. As a result, departments or units of general dental practice or DPC have been established. | General Practice, Dental |
Thirteen clinical isolates of Pasteurella multocida from a variety of different animals and humans were examined for their ability to produce lipase. Lipase substrates used included Tween 20, Tween 40, Tween 80, and Tween 85. Lipase activity was detected in the filtrates of organisms grown to the exponential phase in Roswell Park Memorial Institute-1640 defined media (RPMI-1640), but activity increased in the filtrates when the cultures were allowed to proceed to the stationary phase. All strains examined (except for serotype 2) showed lipase activity against at least one of the Tweens. Tween 40 was the best substrate to demonstrate lipase activity. Pasteurella multocida serotype 8 produced the most active lipase against Tween 40 (3,561.7 units of activity/microgram of protein). This activity continued to increase after P. multocida entered a stationary growth phase. P. multocida lipase activity was optimal at pH 8.0. Lipase activity of P. multocida serotype 8 was eluted from a Sepharose 2B column at several points, indicating that several lipases may be produced in vitro by this organism. These data demonstrate that clinical isolates of P. multocida produce lipase; therefore, this enzyme should be considered a potential virulence factors for this organism. | Pasteurella multocida |
Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with invasive and metastatic characteristics and poor prognosis. Intracellular protein homeostasis is associated with invasion and metastasis of pancreatic cancer, but the specific molecular mechanism remains unclear. Our previous studies have revealed that DNAJB11, a key protein in protein homeostasis, is secreted by exosomes in the supernatant of dissociated pancreatic cancer cells with high metastasis. The results from transcriptome sequencing and co-immunoprecipitation (Co-IP)-based liquid chromatography with tandem mass spectrometry (LC-MS/MS) showed that depletion of DNAJB11 levels could increase HSPA5 expression and induce endoplasmic reticulum stress through the PRKR-like endoplasmic reticulum kinase signaling pathway in pancreatic cancer cells. Furthermore, exosomal DNAJB11 promoted cell development of PC cells in vitro and in vivo. In addition, exosomal DNAJB11 could regulate the expression of EGFR and activate the downstream MAPK signaling pathway. Clinical blood samples were collected to evaluate the potential of exosome DNAJB11 as a diagnostic biomarker and therapeutic target for the treatment of pancreatic cancer. This study could provide a new theoretical basis and potential molecular targets for the treatment of pancreatic cancer. | HSP40 Heat-Shock Proteins |
Renal Cell Carcinoma is the third most common malignoma in urology. Only little is known about the etiology and risk factors; the age peak lies at 60 and twice as many men than women are affected. The clinical picture presents with a wide spectrum. Over one third of all tumours are detected accidentally by ultrasound or computed tomography in asymptomatic patients. Most common symptoms are hematuria and flank pain, the classical trials including in addition a palpable mass is rare and by mo means an early symptom. Paraneoplastic syndromes include unspecific (increased blood sedimentation rate, weight loss, fever) and endocrine symptoms (hypertension, polyglobulia, hypercalcemia). Diagnosis is based on imaging procedures. By means of sonography renal cysts may be separated from solid, space-occupying tumors. For the latter CT plays a decisive role for staging, therapeutic planning and prognosis. Further radiologic investigations (angiography, MRI) are indicated only in special situations. Rarely a biopsy is necessary for the distinction between renal cell carcinoma and metastases of other primary tumors. The only curative treatment of localized carcinoma is radical nephrectomy. Partial resection is indicated in cases of a single kidney, bilateral tumors and possibly also for tumors smaller than 4 cm in diameter. Radiotherapy is only initiated for palliation of painful skeletal metastases. In case of distant metastases--mainly pulmonary--nephrectomy should only be performed if systemic treatment is planned or if local complaints (pain, hematuria leading to anemia) exist. Chemotherapeutic drugs have no influence on survival. The effect of gestagens on life quality is questionable. Adoptive immunotherapy with cytokines (Interferon-alpha, interleukin-2) appears most promising. These substances, however, not yet been introduced into routine therapy should only be used in prospective studies. Furthermore, renal cell carcinoma is a potential candidate for gene therapy. After tumor nephrectomy follow-up investigations should be performed twice a year, because of the possibility of curative surgical treatment of late solid metastases. Prognosis of tumors restricted to the organ is good. Five year survival after operation is about 90%. However, is distant metastases exist already at the time of diagnosis 5 year survival drops to less than 10%. | Kidney Neoplasms |
Twenty-two elbows in 20 patients with persistent lateral pain due to epicondylitis had release of the common extensor origin and decortication of the lateral epicondyle. Specimens taken from the lateral epicondyle were examined histologically and compared with controls, and patients were reviewed clinically 2 (1/2-4) years after operation. Following surgery, symptoms were improved in 17 patients. Histologic examination of the bone-tendon junction revealed evidence of a repair response of variable degree, the most frequent features being mucopolysaccharide infiltration and bone formation. Fibrofatty degenerative changes were also present in some cases. There was no correlation between the intensity of the histologic reaction and the clinical outcome. | Tennis Elbow |
Copper ions can catalyze the production of free oxygen radicals (*OH and *OOH) similar to iron ions. The capacity to initiate oxidative damage is most commonly attributed to Cu-induced toxicity in copper-related diseases where there is an increase in copper levels and also when Cu homeostasis and regulation are disrupted. An antioxidant/chelator inhibiting Cu-induced oxidative damage could play a significant role in the treatment of such Cu-related diseases. Deferiprone has high affinity for copper binding and can be considered for the potential treatment of copper toxicity and overloading conditions, such as Wilson's disease. In the present study, the ability of deferiprone to inhibit the production of hydroxyl radicals catalyzed by copper ions was elucidated using an Electron Paramagnetic Resonance (EPR) spin trapping technique. The values of g-factors and hyperfine splitting constants were calculated for Cu(II)-deferiprone 1:1 complex: (a = 58.5 G, g = 2.1667) and 1:2 complex: (a = 73.0 G, g = 2.1378). The TMIO spin trap (2,2,4-trimethyl-2H-imidazole-1-oxide) was used for the detection of free radicals formed in Fenton-like copper-catalyzed reactions. It was demonstrated that the interaction of deferiprone with Cu(2+) ions completely inhibited hydroxyl radical (*OH) production in the presence of hydrogen peroxide. It was found also that deferiprone inhibits Cu-induced oxidation of linoleic acid in micellar solution. In addition to existing data for water solutions, the affinity of deferiprone for copper binding in non-aqueous environment has been elucidated. | Deferiprone |
Early events of the retroviral life cycle are the targets of many host restriction factors that have evolved to prevent establishment of infection. Incoming retroviral DNAs are transcriptionally silenced before integration in most cell types, and efficient viral gene expression occurs only after formation of the provirus. The molecular machinery for silencing unintegrated retroviral DNAs of HIV-1 remains poorly characterized. Here, we identified the histone chaperones CHAF1A and CHAF1B as essential factors for silencing of unintegrated HIV-1 DNAs. Using RNAi-mediated knockdown (KD) of multiple histone chaperones, we found that KD of CHAF1A or CHAF1B resulted in a pronounced increase in expression of incoming viral DNAs. The function of these two proteins in silencing was independent of their interaction partner RBBP4. Viral DNA levels accumulated to significantly higher levels in CHAF1A KD cells over controls, suggesting enhanced stabilization of actively transcribed DNAs. Chromatin immunoprecipitation assays revealed no major changes in histone loading onto viral DNAs in the absence of CHAF1A, but levels of the H3K9 trimethylation silencing mark were reduced. KD of the H3K9me3-binding protein HP1gamma accelerated the expression of unintegrated HIV-1 DNAs. While CHAF1A was critical for silencing HIV-1 DNAs, it showed no role in silencing of unintegrated retroviral DNAs of mouse leukemia virus. Our study identifies CHAF1A and CHAF1B as factors involved specifically in silencing of HIV-1 DNAs early in infection. The results suggest that these factors act by noncanonical pathways, distinct from their histone loading activities, to mediate silencing of newly synthesized HIV-1 DNAs. | Chromatin Assembly Factor-1 |
INTRODUCTION: The defatted seed meal of Camellia oleifera Abel., which contains saponins, is used extensively in aquaculture to eliminate unwanted fish and harmful insects during the cultivation of prawns, and as a molluscicide to control Pomacea canaliculata Lamarck. For the quality control of such tea seed meal products, a method for the determination of saponin content is required. OBJECTIVE: To develop a simple, sensitive and specific method for the quantitative determination of saponins in tea seed meal using high-performance thin layer chromatography and densitometry. METHODOLOGY: Powdered tea seed meal samples were extracted with methanol, filtered, evaporated to dryness and the residue taken up in methanol. Samples, together with methanolic solutions of saponin standard, were analysed by HPTLC on silica gel layers eluted with ethyl acetate:methanol:water (6:3:1.5, v/v/v) and detected at 214 nm. The amounts of saponins were determined from the respective calibration curves obtained by plotting the concentrations of saponin standard against peak area. RESULTS: Tea saponin peaks were detected at about R(f )0.40. Good linearity was observed in the range of 0.9-22.2 microg/spot with a correlation coefficient of 0.9978. The limits of detection and quantification were 0.87 and 2.90 microg/spot, respectively. The content of tea saponins in 10 tested samples was found to be between 13.1 and 21.1% w/w. CONCLUSION: The assay proved to be a specific, sensitive and inexpensive method for the quality control of saponins in tea seed meal. | Tea |
Cooperative breeding is an extreme form of cooperation that evolved in a range of lineages, including arthropods, fish, birds, and mammals. Although cooperative breeding in birds is widespread and well-studied, the conditions that favored its evolution are still unclear. Based on phylogenetic comparative analyses on 3,005 bird species, we demonstrate here that family living acted as an essential stepping stone in the evolution of cooperative breeding in the vast majority of species. First, families formed by prolonging parent-offspring associations beyond nutritional independency, and second, retained offspring began helping at the nest. These findings suggest that assessment of the conditions that favor the evolution of cooperative breeding can be confounded if this process is not considered to include 2 steps. Specifically, phylogenetic linear mixed models show that the formation of families was associated with more productive and seasonal environments, where prolonged parent-offspring associations are likely to be less costly. However, our data show that the subsequent evolution of cooperative breeding was instead linked to environments with variable productivity, where helpers at the nest can buffer reproductive failure in harsh years. The proposed 2-step framework helps resolve current disagreements about the role of environmental forces in the evolution of cooperative breeding and better explains the geographic distribution of this trait. Many geographic hotspots of cooperative breeding have experienced a historical decline in productivity, suggesting that a higher proportion of family-living species could have been able to avoid extinction under harshening conditions through the evolution of cooperative breeding. These findings underscore the importance of considering the potentially different factors that drive different steps in the evolution of complex adaptations. | Birds |
A mathematical model is described which is appropriately constructed to calculate effluxes of radionuclides from agricultural and natural ecosystems. The application of this model is demonstrated by estimating effluxes in the Bragin region and in the Narovlya region in the Republic of Belarus both highly affected by the Chernobyl accident fallout. Depending on the nature of the area and the deposition, the total efflux and the exported radioactivity are calculated. It is shown that the exported radioactivity for natural foodstuffs represents more than 64% (Bragin region) and 86% (Narovlya region) of the total 137Cs efflux, and for agricultural products 2.7% and 2.3%, respectively. The contribution of the different foodstuffs deriving from natural and agricultural used land to the individual and collective dose for 137Cs and 90Sr are estimated and presented. In the Bragin region for the collective annual dose the highest contribution is due to milk and meat consumption (137Cs) and flour and milk (90Sr), for individual annual dose milk and mushrooms (137Cs), and milk and flour (90Sr) contribute most. In the Narovlya region this contribution for the collective and individual annual dose is due to milk and mushroom consumption (137Cs) and flour and milk (90Sr)." | Food Contamination, Radioactive |
BACKGROUND: Pupillary block induced by silicon oil in vitrectomized patients is a common condition usually treated with Nd-YAG laser iridotomy or with surgical removal of silicon oil. CASE REPORT: A case of silicone oil pupillary block glaucoma successfully treated with a 30 G needle transfixion technique is described. We performed a non-complicated vitrectomy surgery for retinal detachment with proliferative vitreoretinopathy that included lensectomy, inferior peripheral iridectomy, and silicone oil injection. After surgery, the iridectomy became occluded with fibrous tissue and the intraocular pressure raised to 50 mmHg. After an initial Nd-YAG iridotomy was unsuccessful, we passed a 30 Ga needle through the sclerocorneal limbus and cut the fibrous tissue that blocked the iridectomy. This procedure restored the aqueous humor flow through the iridectomy, pushed back the silicone oil bubble into the vitreous cavity and lowered the intraocular pressure to normal levels. CONCLUSIONS: 30 Ga needle transfixion technique could be an effective, low cost, simple alternative for the treatment of silicone oil pupillary block in aphakic patients. | Iridectomy |
The protective effects of a combination of dopamine and furosemide were studied in dogs during the initial phase of acute renal failure (ARF) induced by intravenous uranyl nitrate (10 mg/kg). Fifteen minutes after injection of the nephrotoxin, and infusion of dopamine (3 micrograms/kg/min), furosemide (1 mg/kg/bolus followed by 1 mg/kg/hr), or both drugs simultaneously were given for 6 hours. Exogenous creatinine clearance was measured for 6 hours, and the intrarenal blood flow was measured with radioactive microspheres before and 3 hours after the induction of ARF. Treatment with both dopamine and furosemide produced renal vasodilatation, high urine flow rate, and attenuation of the fall in GRF seen in untreated animals. In contrast, single use of dopamine or furosemide was totally ineffective in producing renal vasodilation, a diuresis, or the maintenance of the GFR. These data indicate that dopamine plus furosemide have a synergistic effect in preventing the early pathophysiologic changes associated with ARF in this animal model. Maintenance of a high GFR correlated best with the enhancement of solute excretion and urine flow rate. Potential protective effects of dopamine plus furosemide in other models of ARF deserve careful investigation. | Uranyl Nitrate |
Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are standard first-line treatments for metastatic ER(+) breast cancer. However, acquired resistance to CDK4/6i invariably develops, and the molecular phenotypes and exploitable vulnerabilities associated with resistance are not yet fully characterized. We developed a panel of CDK4/6i-resistant breast cancer cell lines and patient-derived organoids and demonstrate that a subset of resistant models accumulates mitotic segregation errors and micronuclei, displaying increased sensitivity to inhibitors of mitotic checkpoint regulators TTK and Aurora kinase A/B. RB1 loss, a well-recognized mechanism of CDK4/6i resistance, causes such mitotic defects and confers enhanced sensitivity to TTK inhibition. In these models, inhibition of TTK with CFI-402257 induces premature chromosome segregation, leading to excessive mitotic segregation errors, DNA damage, and cell death. These findings nominate the TTK inhibitor CFI-402257 as a therapeutic strategy for a defined subset of ER(+) breast cancer patients who develop resistance to CDK4/6i." | M Phase Cell Cycle Checkpoints |
Protein N-terminal acetylation is a widespread modification in eukaryotes catalyzed by N-terminal acetyltransferases (NATs). The various NATs and their specific substrate specificities and catalytic mechanisms are far from fully understood. We here describe an in vitro method based on reverse-phase HPLC to quantitatively measure in vitro acetylation of NAT oligopeptide substrates, enabling the determination of NAT specificity as well as kinetic parameters." | N-Terminal Acetyltransferase E |
A new prehardening process has been demonstrated by passing falling drops through a fine mist of hardening solution, in which drops were generated as monodispersed and concentric two-phase particles. A mixture of vegetable oil and vitamin E has been encapsulated using calcium alginate for rapid hardening and hydroxy propyl methyl cellulose acetate succinate for slow hardening. Both hardening agents produced satisfactory stable encapsulation. | Acids, Aldehydic |
OBJECTIVES: To test the hypothesis that maxacalcitol, vitamin D3 analog, would ameliorate detrusor overactivity (DO) induced by retinyl acetate instillation; to test the outcome of the combined administration of maxacalcitol and the rho kinase inhibitor - GSK 269962, amlodipine besylate, or oxybutynin chloride in this model. METHODS: The rats were treated with maxacalcitol for 14 days. Then, cystometric studies were performed during which the animals were administered test compounds. RESULTS: Maxacalcitol in a dose of 30 but not 15 microg/kg/day induced reduction in DO index, non-voiding contractions frequency (FNVC), and amplitude (ANVC), while increasing volume threshold to elicit non-voiding contractions (VTNVC). The 14-day-long administration of maxacalcitol at a dose of 15 microg/kg/day to animals, followed by GSK 269962 at a single dose of 10 mg/kg, led to a statistically significant reduction of intercontraction interval and bladder compliance, and an increase in DO index, without any effect on ANVC, FNVC, and VTNVC. The assessment of the combined effect of maxacalcitol (15 microg/kg/day) and amlodipine besylate (0.25 mg/kg) demonstrated an increase in intercontraction interval, bladder compliance and VTNVC, with a decrease in FNVC. No statistically significant changes were found in DO index and ANVC. The combined outcome of administering maxacalcitol (15 microg/kg/day) and oxybutynin chloride (0.25 mg/kg) did not show any statistically significant value of the measured cystometric parameters. CONCLUSION: The outcomes of maxacalcitol administration can be the result of 3 mechanisms, that is, the upregulation of L-type Ca(2+) channels, the inhibition of the rho kinase pathway, and a so far unknown central mechanism. | Calcitriol |
Degeneration or loss of inner ear hair cells (HCs) is irreversible and results in sensorineural hearing loss (SHL). Human-induced pluripotent stem cells (hiPSCs) have been employed in disease modelling and cell therapy. Here, we propose a transcription factor (TF)-driven approach using ATOH1 and regulatory factor of x-box (RFX) genes to generate HC-like cells from hiPSCs. Our results suggest that ATOH1/RFX1/RFX3 could significantly increase the differentiation capacity of iPSCs into MYO7A(mCherry)-positive cells, upregulate the mRNA expression levels of HC-related genes and promote the differentiation of HCs with more mature stereociliary bundles. To model the molecular and stereociliary structural changes involved in HC dysfunction in SHL, we further used ATOH1/RFX1/RFX3 to differentiate HC-like cells from the iPSCs from patients with myoclonus epilepsy associated with ragged-red fibres (MERRF) syndrome, which is caused by A8344G mutation of mitochondrial DNA (mtDNA), and characterised by myoclonus epilepsy, ataxia and SHL. Compared with isogenic iPSCs, MERRF-iPSCs possessed ~42-44% mtDNA with A8344G mutation and exhibited significantly elevated reactive oxygen species (ROS) production and CAT gene expression. Furthermore, MERRF-iPSC-differentiated HC-like cells exhibited significantly elevated ROS levels and MnSOD and CAT gene expression. These MERRF-HCs that had more single cilia with a shorter length could be observed only by using a non-TF method, but those with fewer stereociliary bundle-like protrusions than isogenic iPSCs-differentiated-HC-like cells could be further observed using ATOH1/RFX1/RFX3 TFs. We further analysed and compared the whole transcriptome of M1(ctrl)-HCs and M1-HCs after treatment with ATOH1 or ATOH1/RFX1/RFX3. We revealed that the HC-related gene transcripts in M1(ctrl)-iPSCs had a significantly higher tendency to be activated by ATOH1/RFX1/RFX3 than M1-iPSCs. The ATOH1/RFX1/RFX3 TF-driven approach for the differentiation of HC-like cells from iPSCs is an efficient and promising strategy for the disease modelling of SHL and can be employed in future therapeutic strategies to treat SHL patients. | Regulatory Factor X1 |
The possibility of developing coronary steal in patients having coronary artery bypass graft (CABG) using internal thoracic artery (ITA) and ipsilateral upper extremity arteriovenous (AV) hemodialysis shunt has been reported. The impact of this phenomenon on clinical outcomes is uncertain. The aim of this study was to investigate an association between the AV dialysis shunt location regarding the side of the ITA CABG and clinical outcomes. This retrospective cohort study included chronic hemodialysis patients having ITA CABG and upper extremity AV shunt. The patients were divided into two groups: those with ipsilateral and those with contralateral location of ITA CABG and AV shunt. The outcomes were: death from any cause, cardiac death and a first cardiac event. In a group of 112 chronic hemodialysis patients having CABG, 32 had an ipsilateral and 25 had a contralateral location of ITA CABG and an upper extremity AV shunt. Significantly more cardiac events occurred in the group with an ipsilateral compared to a contralateral location of ITA CABGs and dialysis AV shunts (hazard ratio, 2.16 [95% CI, 1.11 to 4.19], P = 0.023). There was no difference between the groups in the all cause mortality risk (hazard ratio, 1.005 [95% CI, 0.43 to 2.37], P = 0.990) or the risk of cardiac death (hazard ratio, 2.43 [95% CI, 0.64 to 9.17], P = 0.191). The ipsilateral location of a CABG with the use of ITA and upper extremity AV hemodialysis shunt may be associated with increased risk of cardiac events." | Coronary-Subclavian Steal Syndrome |
Women are substantially underrepresented in senior and leadership positions in medicine and experience gendered challenges in their work settings. This systematic review aimed to synthesise research that has evaluated interventions for improving gender equity in medicine. English language electronic searches were conducted across MEDLINE, CINAHL, Academic Search Complete, PsycINFO and Web of Science. Reference list screening was also undertaken. Peer-reviewed studies published between 2000 and March 2020 that evaluated interventions to improve gender equity, or the experiences of women, in academic or clinical medicine were reviewed. Dual reviewer data extraction on setting, participants, type of intervention, measurement and outcomes was completed. Methodological rigour and strength of findings were evaluated. In total, 34 studies were included. Interventions were typically focused on equipping the woman (82.4%), that is, delivering professional development activities for women. Fewer focused on changing cultures (20.6%), ensuring equal opportunities (23.5%) or increasing the visibility or valuing of women (23.5%). Outcomes were largely positive (87.3%) but measurement typically relied on subjective, self-report data (69.1%). Few interventions were implemented in clinical settings (17.6%). Weak methodological rigour and a low strength of findings was observed. There has been a focus to-date on interventions which Equip the Woman Interventions addressing systems and culture change require further research consideration. However, institutions cannot wait on high quality research evidence to emerge to take action on gender equity. Data collated suggest a number of recommendations pertaining to research on, and the implementation of, interventions to improve gender equity in academic and clinical settings. | Gender Equity |
The serine protease thrombin (EC 3.4.21.5) is central to the maintenance of haemostatic balance through its coagulant, anticoagulant and platelet activating properties. In addition, this enzyme affects numerous cellular responses in a wide variety of cells, such as cell proliferation, cytokine and growth factor release, lipid metabolism and tissue remodelling. A family of G-protein-coupled protease-activated receptors (PARs) mediates these cellular actions of thrombin. While thrombin can activate three of the four PAR family members, PAR-1 represents the primary thrombin-responsive receptor in human cells. The expression of PAR-1 in platelets, the vasculature and myocardium, in cells within atherosclerotic plaque and tissues after vascular injury, indicates that this receptor plays an important role during the response to tissue injury and associated inflammatory processes. With the development of PAR-deficient mice and small-molecule antagonists, it is now clear that intervening in processes mediated by PAR-1 presents a new approach to treating a variety of disorders dependent on thrombin generation, including thrombosis and restenosis. The full potential of PAR-1 antagonists has yet to be realised, but the promise of novel therapeutics that modulate receptor function rather than thrombin's proteolytic activity, provides an alternative and, perhaps, more desirable means to dampen the pathological effects of thrombin." | Receptors, Proteinase-Activated |
Mutations in the melanocortin-4 receptor (MC4R) gene are the most frequent monogenic causes of severe obesity. Most mutations have been described as heterozygous with loss of function, suggesting that haploinsufficiency is the most likely mechanism of dominant inheritance. We detected a heterozygous mutation, D90N, in a patient with severe early-onset obesity. Functional characterization of the mutant receptor revealed normal cell-surface expression and binding properties but loss of signal transduction activity. In coexpression studies of wild-type (WT)-MC4R and D90N, the mutant receptor had a dominant-negative effect on WT-receptor function. Further investigation of this effect with sandwich enzyme-linked immunosorbent assays and fluorescence resonance energy transfer studies showed that the WT-MC4R and the D90N mutant form homodimers and heterodimers. We hypothesize that the dominant-negative effect of the D90N mutation is caused by a functionally altered WT-MC4R/D90N receptor heterodimer. These findings necessitate the reinvestigation of other heterozygous MC4R missense mutations to discriminate between haploinsufficiency and a dominant-negative effect. The finding of receptor dimerization highlights a more complex hypothalamic signaling network governing the regulation of body weight." | Receptor, Melanocortin, Type 4 |
The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood, and treatment remains difficult. We have previously reported that colon-specific dorsal root ganglion (DRG) neurons were hyperactive in a rat model of IBS induced by neonatal colonic inflammation (NCI). This study was designed to examine plasticity of voltage-gated Na(+) channel activities and roles for the endogenous hydrogen sulfide-producing enzyme cystathionine beta-synthetase (CBS) in chronic visceral hyperalgesia. Abdominal withdrawal reflex (AWR) scores were recorded in response to graded colorectal distention in adult male rats as a measure of visceral hypersensitivity. Colon-specific DRG neurons were labeled with 1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate and acutely dissociated for measuring Na(+) channel currents. Western blot analysis was employed to detect changes in expressions of voltage-gated Na(+) (Na(V)) channel subtype 1.7, Na(V)1.8, and CBS. NCI significantly increased AWR scores when compared with age-matched controls. NCI also led to an ~2.5-fold increase in Na(+) current density in colon-specific DRG neurons. Furthermore, NCI dramatically enhanced expression of Na(V)1.7, Na(V)1.8, and CBS in colon-related DRGs. CBS was colocalized with Na(V)1.7 or -1.8 in colon-specific DRG neurons. Administration of O-(carboxymethyl)hydroxylamine hemihydrochloride (AOAA), an inhibitor for CBS, remarkably suppressed Na(+) current density and reduced expression of Na(V)1.7 and Na(V)1.8. More importantly, intraperitoneal or intrathecal application of AOAA attenuated AWR scores in NCI rats in a dose-dependent manner. These data suggest that NCI enhances Na(+) channel activity of colon DRG neurons, which is most likely mediated by upregulation of CBS expression, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS. | Reflex, Abdominal |
Colony opacity variants were detected for type III group B streptococci (GBS). Transparent colonies predominate in the parent GBS, with occasional colonies having opaque portions. Two stable opaque variants (1.1 and 1.5) were compared with three transparent clones (1.2, 1.3, and 1.4). All grew well on blood agar and on GC medium, but variant 1.1 failed to grow on Todd-Hewitt medium. Scanning and transmission electron microscopy demonstrated that colony opacity correlated with bacterial aggregation status, with opaque variants forming longer and more organized chains. Opaque-transparent switches were observed in both directions for most variants, with transparent to opaque noted most frequently, but 1.5 did not switch at all. Switching of the opacity phenotype was observed both in vitro and in neonatal mice. Relationships between colony opacity and several cell surface phenomena were explored. (i) Opaque variant 1.1 had two surface proteins (46 and 75 kDa) that were either unique or greatly overexpressed. (ii) Variant 1.1 was deficient in type III polysaccharide, while 1.5 lacked group B antigen. Diminished capsular polysaccharide of variant 1.1 was reflected in reduced negative electrophoretic mobility and in increased buoyant density. (iii) Transparent variant colonies growing closest to a penicillin disk were opaque, but colonial variants did not differ in their sensitivity to penicillin. These data indicate that GBS can exist in both opaque and transparent forms, with opaque appearance occurring by multiple routes. Opaque variants grow poorly on Todd-Hewitt medium generally used for isolation of GBS, so any possible relationships between opacity variation and pathogenesis of GBS infection are unknown. | Bacterial Capsules |
OBJECTIVES: It has been reported that matrix metalloproteinase, MMP-3 may play a significant role in the pathophysiology of mental disorders. However, there are no data on the level of MMP-3 in people suffering from schizophrenia, or its influence on the mental state of these people. The aim of this study was to investigate the effect of an antipsychotic treatment on the blood levels of MMP-3, as well as investigating its relationship with insight into schizophrenia. METHODS: Thirty people with schizophrenia were included in the study. The concentration of MMP-3 in the blood serum was assessed using enzyme-linked immunosorbent assay. Insight into the disease was assessed using the Beck Cognitive Insight Scale. RESULTS: The antipsychotic treatment applied decreased the levels of MMP-3 in patients with schizophrenia (p = 0.005), however, the statistically significant interaction (p = 0.02) indicates that the decrease only concerned men. There was also a statistically significant correlation between the level of MMP-3 and insight into the disease (p = 0.02). CONCLUSION: MMP-3 may be associated with gender, treatment and symptoms in schizophrenic patients.KEY POINTSMMP3 could be used as a potential biomarker for schizophrenia.The level of MMP-3 decreased due to the applied antipsychotic treatment.The higher the level of MMP-3 in a group of people with schizophrenia, the better insight into their disease. | Matrix Metalloproteinase 3 |
Two pairs of diastereoisomers (1/2 and 3/4) were isolated from the fruits of Rubus idaeus L. (Rosaceae). Their structures were elucidated on the basis of extensive spectroscopic analyses. Then chiral-phase HPLC resolution gave 1a/1b-4a/4b. Their absolute configurations were determined by comparison of the experimental ECD with the calculated data. Moreover, all isolated compounds were investigated for the neuroprotective effects against H(2)O(2)-induced neurotoxicity in human neuroblastoma SH-SY5Y cells, and 2a (66.04%) exhibited moderate neuroprotective effects, better than trolox (60.54%) at the concentration of 25 muM. | Rubus |
The World Health Organisation (WHO) updated guidelines on the management of severe acute malnutrition in infants and children (2013) recommends antibiotic treatment of uncomplicated severe acute malnutrition (SAM) in the community setting. As community-based treatment is gaining ground, this evidence review looks at the emerging data to improve the decision-making process. The databases of Pubmed, Google Scholar, Cochrane Database of Systematic Review were searched for experimental and observational studies in the English literature for the period of 2011-2021. The search identified seven studies: two interventional and five observational. Six of these studies showed significant improvement in recovery rates using weight for height Z-score-2. Emerging evidence supports the continuation of antibiotic treatment for uncomplicated SAM in out-patient settings, as recommended in the WHO guideline of 2013. | Severe Acute Malnutrition |
The laccase gene from Pycnoporus sanguineus was cloned and inserted between the strong Pcbh1 promoter and the Tcbh1 terminator from Trichoderma reesei to form the recombinant plasmid pCH-lac. Using Agrobacterium-mediated technique, the pCH-lac was integrated into the chromosomes of T. reesei. Twenty positive transformants were obtained by employing hygromycin B as a selective agent. PCR was used to confirm that the laccase gene was integrated into the chromosomal DNA of T. reesei. Laccase production by recombinant transformants was performed in shaking flasks, and the activity of laccase reached 8.8 IU/mL after 96-h fermentation under a batch process, and 17.7 IU/mL after 144-h fermentation using a fed-batch process. SDS-PAGE analysis of the fermentation broth showed that the molecular mass of the protein was about 68 kDa, almost the same as that of the laccase produced by P. sanguineus, which indicated that laccase was successfully expressed in T. reesei and secreted out of the cells. The laccase produced by the recombinant T. reesei showed good thermal stability, and could degrade the toxic phenolic material bisphenol A efficiently, after 1-h reaction with 0.06 IU/mL laccase and 0.5 mmol/L ABTS as the mediator at 60 degrees C and pH 4.5, the degradation rate reached 95%, which demonstrated that it had great potential value in treating the household garbage and wastewater containing the bisphenol A. | Pycnoporus |
The Energy Committee of the Royal Swedish Academy of Sciences has in a series of projects gathered information and knowledge on renewable energy from various sources, both within and outside the academic world. In this article, we synthesize and summarize some of the main points on renewable energy from the various Energy Committee projects and the Committee's Energy 2050 symposium, regarding energy from water and wind, bioenergy, and solar energy. We further summarize the Energy Committee's scenario estimates of future renewable energy contributions to the global energy system, and other presentations given at the Energy 2050 symposium. In general, international coordination and investment in energy research and development is crucial to enable future reliance on renewable energy sources with minimal fossil fuel use. | Renewable Energy |
BACKGROUND AND OBJECTIVES: Photodynamic therapy causes direct cytotoxicity to malignant cells within a tumor. Photodynamic therapy (PDT) can also have both direct and indirect effects upon various non-malignant components of the tumor microenvironment. This action can lead to PDT-mediated angiogenesis and inflammation, which are emerging as important determinants of PDT responsiveness. STUDY DESIGN/MATERIALS AND METHODS: Preclinical studies have been performed to document how PDT modulates the tumor microenvironment. The expression, function, and treatment relevance of angiogenic growth factors, proteinases, and inflammatory molecules have been monitored following PDT using mouse tumor models. RESULTS: Photofrin-mediated PDT was shown to be a strong activator of VEGF, MMPs, and COX-2 derived prostaglandins within the tumor microenvironment. Inhibitors that target these angiogenic and pro-survival molecules can enhance the effectiveness of PDT. CONCLUSIONS: Improvements in PDT tumor responsiveness may be achieved by employing combined modality regimens targeting malignant cells as well as treatment-induced angiogenesis and/or inflammation. | Dihematoporphyrin Ether |
Anthrax is a recessive infectious disease caused by the bacterium Bacillus anthracis, and is primarily a zoonotic disease. Until recently, Bacillus anthracis infections were relatively infrequent and confined to agrarian communities in underdeveloped countries. No anthrax cases were reported in Changchun City in the past few decades until a male patient from the Inner Mongolia Autonomous Region presented the anthrax disease manifestation. This paper describes an anthrax patient's diagnosis, isolation and treatment which involved institutions in two different Chinese provinces; the foci epidemiological investigation alongside with the outbreak management process, which is of great significance to control the spread of the recessive infection is also described. | Anthrax |
BACKGROUND: As interest in skin beauty increases, the development of new skin whitening agents has attracted substantial attention; however, the action mechanism of the agents developed so far remains largely unknown. Tranexamic acid (TXA) is commonly being used to reduce melanin synthesis in patients with melasma and also used as a raw material for functional whitening cosmetics, although its action mechanism is poorly understood. Autophagy has been well known to be essential for tissue homeostasis, adaptation to starvation, and removal of dysfunctional organelles or pathogens. Recent studies have shown that autophagy regulators might have prominent roles in the initial formation stage of the melanosome, a lysosome-related organelle synthesizing melanin pigments. However, there is still no direct evidence showing a relationship between the activation of the autophagy system and the melanogenesis. OBJECTIVE: To investigate whether TXA can inhibit melanogenesis through the activation of autophagy in a melanoma cell line. METHODS: B16-F1 melanoma cells were treated with TXA and the levels of autophagy- and melanogenesis-related proteins were determined by Western blottings. The direct effect of TXA-mediated autophagy activation on melanin production was further evaluated by transfecting the cells with 60 pmols of small interfering RNAs (siRNAs)-targeting the mechanistic target of rapamycin (mTOR) and the autophagy-related protein 5 (Atg5). RESULTS: The results of Western blottings showed that TXA enhanced the production of autophagy-related proteins such as mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK)1/2, Beclin-1, Atg12, and light chain 3 (LC3) I-II, whereas it decreased the synthesis of the mTOR complex. Confocal microscopy clearly showed that TXA treatment resulted in the formation of autophagosomes in B16-F1 cells, as revealed by immunostaining with an anti-LC3 antibody. The production of melanogenesis-associated proteins, including microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein 1 and 2 (TRP1/2), were clearly downregulated by the treatments with TXA. These results suggest that TXA can mediate a decrease in melanin synthesis by alleviating the production of tyrosinase and TRP1/2, along with lowered MITF protein levels. Furthermore, after treatment with TXA, siRNAs- targeting to mTOR and Atg5 increased melanin synthesis by 20% and 40%, respectively, compared to that in non-transfected cells, in a dose-dependent manner. These results further confirmed that TXA can inhibit melanogenesis by activating the autophagy system. CONCLUSION: Collectively, the results demonstrate that TXA can reduce melanin synthesis in melanoma B16-F1 cells by activating the ERK signaling pathway and the autophagy system. | Autophagy-Related Protein 5 |
This study reports an effective method for controlling substance-release sites of hydrogel. Glycidyl methacrylate, which contains two functional groups, namely, double-bond acrylate and epoxide, is photografted on a hydrogel surface through hydrogen abstraction photopolymerization due to the existence of a hydrogen donor, such as an amine, in the hydrogel matrix. The remaining epoxide group crosslinks the polymer chain of polyglycidyl methacrylate. Substance release of hydrogel is changed due to the altered surface texture of hydrogel. Rate and site-controlled substance release are achieved by controlling the thickness and site of surface grafting and the extent of epoxide ring opening. This study may provide a novel method for achieving hydrogel function or modified performance of other biomaterials to meet biological activity requirements." | Hydrogel, Polyethylene Glycol Dimethacrylate |
AIMS: The categories in the comprehensive lipid and risk management guidelines were proposed by the Japan Atherosclerosis Society (JAS Guidelines 2017), which adopted the estimated 10 year absolute risk of coronary artery disease (CAD) incidence in the Suita score. We examined whether those categories were concordant with the degree of arterial stiffness. METHODS: In 2014, the cardio-ankle vascular index (CAVI), an arterial stiffness parameter, was measured in 1,972 Japanese participants aged 35-74 years in Tsuruoka City, Yamagata Prefecture, Japan. We examined the mean CAVI and the proportion and odds ratios (ORs) of CAVI >/= 9.0 on the basis of the following three management classifications using the analysis of variance and logistic regression: Category I (Low risk)," "Category II (Middle risk)," and "Category III (High risk)." RESULTS: The mean CAVI and proportion of CAVI >/= 9.0 were 8.6 and 34.8% among males and 8.1 and 18.3% among females, respectively. The mean CAVI and proportion of CAVI >/= 9.0 were associated with an estimated 10 year absolute risk for CAD among males and females, excluding High risk for females. These results were similar to the management classification by the guideline: the multivariable-adjusted ORs (95% confidence intervals) of CAVI >/= 9.0 among Category II and Category III compared with those among Category I were 2.96 (1.61-5.43) and 7.33 (4.03-13.3) for males and 3.99 (2.55-6.24) and 3.34 (2.16-5.16) for females, respectively. CONCLUSIONS: The risk stratification, which was proposed in the JAS Guidelines 2017, is concordant with the arterial stiffness parameter." | Cardio Ankle Vascular Index |
The aim of the present work was to study the action of clofibrate, known as peroxisomal proliferator, on the intestinal peroxisomes in the foetus of treated pregnant females. The Novikoff technique (catalase activity detection) shows an increase in the number and size of intestinal peroxisomes in the treated females and in the foetus. Significant differences were observed between enterocyte peroxisomal enzymatic activities (catalase and PBE: peroxisomal bifunctional enzyme) in treated and control females on the one hand, and in the foetus of treated and control mothers on the other. The ultrastructural immunocytochemical study of the PPAR (peroxisome proliferator activated receptor) shows labelling of the enterocyte nucleus and mitochondria by the gold particles." | Peroxisomal Bifunctional Enzyme |
The growing demand for wholesome and nutritious food leads to intensification of production, which in turn can have a detrimental effect on quality and well-being of consumers. For that reason, it is important to develop novel methods of food control which would be characterized by a short time of analysis, adequate sensitivity and relatively low cost. One such technique involves the use of multi-sensory devices called electronic noses. In recent years there has been a rapid development of this method, especially in the area of food control. Electronic olfaction can be successfully used in the analysis of edible oils, in particular in the determination of the product's geographical origin, and in detection of adulteration as well as deterioration caused by external factors. | Food Analysis |
RNA editing alters the nucleotide sequence of an RNA molecule so that it deviates from the sequence of its DNA template. Different RNA-editing systems are found in the major eukaryotic lineages, and these systems are thought to have evolved independently. In this study, we provide a detailed analysis of data on C-to-U editing sites in land plant chloroplasts and propose a model for the evolution of RNA editing in land plants. First, our data suggest that the limited RNA-editing system of seed plants and the much more extensive systems found in hornworts and ferns are of monophyletic origin. Further, although some eukaryotic editing systems appear to have evolved to regulate gene expression, or at least are now involved in gene regulation, there is no evidence that RNA editing plays a role in gene regulation in land plant chloroplasts. Instead, our results suggest that land plant chloroplast C-to-U RNA editing originated as a mechanism to generate variation at the RNA level, which could complement variation at the DNA level. Under this model, many of the original sites, particularly in seed plants, have been subsequently lost due to mutation at the DNA level, and the function of extant sites is merely to conserve certain codons. This is the first comprehensive model for the evolution of the chloroplast RNA-editing system of land plants and may also be applicable to the evolution of RNA editing in plant mitochondria. | Anthocerotophyta |
More than 400 achlorophyllous plant species in 87 genera are parasitic upon fungi, and exploit them as their principle source of carbon. With a few exceptions, most of these myco-heterotrophic plants are now thought to be 'cheats', stealing carbon and nutrients from the mycorrhizal associates of adjacent autotrophic plants. Most myco-heterotrophs are therefore considered to be epiparasitic on green plants. Both the ectomycorrhizal and arbuscular mycorrhizal symbioses have been invaded by myco-heterotrophic epiparasites. DNA analysis is revealing the identities of many of the fungal partners of myco-heterotrophs, and their exceptionally high specificity. Myco-heterotrophs have distinctive stable isotope signatures, which can be used to establish the dependence upon fungal carbon of green plants that are partially myco-heterotrophic. | Mycorrhizae |
Specification of germ cells in mice occurs relatively late in embryonic development. It is initiated by signals that induce expression of Blimp1, a key regulator of the germ cell, in a few epiblast cells of early postimplantation embryos. Blimp1 represses the incipient somatic program in these cells and promotes progression toward the germ cell fate. Blimp1 may also have a role in the maintenance of early germ cell characteristics by ensuring their escape from the somatic fate as well as possible reversion to pluripotent stem cells. | Protein Methyltransferases |
The vanilloid transient receptor potential channel TRPV3 is a putative molecular thermosensor widely considered to be involved in cutaneous sensation, skin homeostasis, nociception, and pruritus. Repeated stimulation of TRPV3 by high temperatures above 50 degrees C progressively increases its responses and shifts the activation threshold to physiological temperatures. This use-dependence does not occur in the related heat-sensitive TRPV1 channel in which responses decrease, and the activation threshold is retained above 40 degrees C during activations. By combining structure-based mutagenesis, electrophysiology, and molecular modeling, we showed that chimeric replacement of the residues from the TRPV3 cytoplasmic inter-subunit interface (N251-E257) with the homologous residues of TRPV1 resulted in channels that, similarly to TRPV1, exhibited a lowered thermal threshold, were sensitized, and failed to close completely after intense stimulation. Crosslinking of this interface by the engineered disulfide bridge between substituted cysteines F259C and V385C (or, to a lesser extent, Y382C) locked the channel in an open state. On the other hand, mutation of a single residue within this region (E736) resulted in heat resistant channels. We propose that alterations in the cytoplasmic inter-subunit interface produce shifts in the channel gating equilibrium and that this domain is critical for the use-dependence of the heat sensitivity of TRPV3. | Protein Subunits |
The incorporation of 6-thioguanine (S6G) into DNA is an essential step in the cytotoxic activity of thiopurines. However, the structural effects of this substitution on duplex DNA have not been fully characterized. Here, we present the solution structures of DNA duplexes containing S6G opposite thymine (S6G.T) and opposite cytosine (S6G.C), solved by high-resolution NMR spectroscopy and restrained molecular dynamics. The data indicate that both duplexes adopt right-handed helical conformations with all Watson-Crick hydrogen bonding in place. The S6G.T structures exhibit a wobble-type base pairing at the lesion site, with thymine shifted toward the major groove and S6G displaced toward the minor groove. Aside from the lesion site, the helices, including the flanking base pairs, are not highly perturbed by the presence of the lesion. Surprisingly, thermal dependence experiments suggest greater stability in the S6G-T mismatch than the S6G-C base pair. | Thioguanine |
The Tat protein controls transcription in lentiviruses such as HIV. A cyclic peptide analog of the RNA binding domain of the bovine immunodeficiency virus (BIV) Tat protein is shown to bind specifically to its target RNA stem loop. NMR data indicate a similar mode of binding of linear and cyclic peptides." | Immunodeficiency Virus, Bovine |
A group of new meiotic division abnormalities affecting processes of phragmoplast centrifugal movement in successive cytokinesis in cereal pollen mother cells is described. These phenotypes present new information about motile phragmoplast formation and operation and confirm our model of centrifugal movements as B-ana-phase modification. | Edible Grain |
We report a case of cystic mesothelioma of the peritoneum in a young male with local recurrences and whose diagnosis was confirmed by standard histological studies and immunohistochemistry. This rare tumor appears generally in young females through abdominal pain and mass. Local recurrences without distant metastases are a feature of this pathology. The adequate treatment requires complete resection. | Mesothelioma, Cystic |
Solid-state fermentation (SSF) with the medicinal higher Basidiomycete Ganoderma lucidum was studied as a strategy to use pine (Pinus radiata D. Don) and poplar (Populus nigra L.) wood chips and sawdust. Fruiting bodies were produced and the value of the biotransformed substrate was assessed. The highest mushroom yield (63 g dry weight per kilogram of dry substrate) was obtained with poplar sawdust and wood chips. Immersion of the bioreactors was a simple watering method that obtained suitable yields. Two morphological types were induced using 2 different incandescent light intensities. High light irradiation induced the highest valued mushroom morphology (as a whole product). Time course study of substrate biodegradation and mycelial growth dynamics indicated that the trophophase lasted 20 days and presented laccase activity of 0.01-0.03 units . g-1. The activity at idiophase was 10 times higher. Aqueous and alkali extracts, as well as carbohydrase enzyme profile activity, revealed differences in the properties of the residual substrate; some related to the substrate source are considered to be of concern for further use of this pretreated biomass. In view of the results obtained, we propose use of SSF of pine and poplar with G. lucidum to profitably recycle softwood by-products from the timber industry. | Reishi |
To investigate the symbiotic roles of the gut microbiota in the fungus-growing termite Macrotermes barneyi, a novel strain with chitinolytic and cellulolytic activity, designated strain an-chi-1(T), was isolated from the hindgut of M. barneyi. Strain an-chi-1(T) grows optimally at 28-30 degrees C, pH 8.0 in PYG medium. On the basis of 16S rRNA gene sequence analysis, this isolate belongs to the genus Cellulomonas with high sequence similarity to Cellulomonas iranensis (99.4%), followed by Cellulomonas flavigena (98.4%), Cellulomonas phragmiteti (97.4%), Cellulomonas oligotrophica (97.2%) and Cellulomonas terrae (97.0%). The DNA-DNA relatedness between an-chi-1(T) and the type strains of C. iranensis and C. flavigena DSM20109(T) are 35.4% and 23.7%, respectively. The major cellular fatty acids are anteiso-C(15:0) and C(14:0). The polar lipid profile consists of diphosphatidylglycerol, phosphatidylinositol mannosides, phosphatidylinositol dimannosides and one unidentified phospholipid. The cell-wall sugar is ribose. The peptidoglycan contains glutamic acid, aspartic acid and alanine. The DNA G+C content is 67.3 mol%. Based on its distinctive phenotypic, phylogenetic, and chemotaxonomic characteristics, an-chi-1(T) represents a novel species of the genus Cellulomonas, for which the name Cellulomonas macrotermitis sp. nov. is proposed. The type strain is an-chi-1(T) (= JCM 31923(T) = CICC 24195(T)). | Cellulomonas |
PURPOSE: To investigate whether trypan blue has a toxic effect on cultured retinal pigment epithelial (retinal pigment epithelium) cells. DESIGN: Experimental study with a direct live/dead cell staining technique using fluorescent dyes. METHODS: Cultured human retinal pigment epithelium cells were exposed for 5 minutes to various concentrations of trypan blue (0.06%, 0.15%, 0.30%), and cell viability was confocally measured. RESULTS: No increased cell death was found in cultures incubated in any of the trypan blue concentrations used. CONCLUSION: These findings indicate that a short exposure of trypan blue does not have a toxic effect on cultured retinal pigment epithelium cells. | Pigment Epithelium of Eye |
The transcription factor EB (TFEB) is a transcription factor of the MiT/TFE family that translocations from the cytoplasm to the nucleus in response to various stimuli, including lysosomal stress and nutrient starvation. By activating genes involved in lysosomal function, autophagy, and lipid metabolism, TFEB plays a crucial role in maintaining cellular homeostasis. Dysregulation of TFEB has been implicated in various diseases, including cancer, neurodegenerative diseases, metabolic diseases, cardiovascular diseases, infectious diseases, and inflammatory diseases. Therefore, modulating TFEB activity with agonists or inhibitors may have therapeutic potential. In this review, we reviewed the recently discovered regulatory mechanisms of TFEB and their impact on human diseases. Additionally, we also summarize the existing TFEB inhibitors and agonists (targeted and non-targeted) and discuss unresolved issues and future research directions in the field. In summary, this review sheds light on the crucial role of TFEB, which may pave the way for its translation from basic research to practical applications, bringing us closer to realizing the full potential of TFEB in various fields." | Basic Helix-Loop-Helix Leucine Zipper Transcription Factors |
The authors examine the characteristic of the standing position and the successive developmental phases of proprioceptive afferent stimuli which lead to the coordination of muscles responsible for the control of static and dynamic balance. Subsequently, they analyze pathological changes due to intrinsic factors which are likely to be involved in dysmorphisms of the spine, and to extrinsic factors such as those brought about by orthotic or surgical intervention on the spine. The authors conclude stressing the clinical and prognostic importance of global evaluation of kinetic alterations resulting from zonal changes in the entire complex of the locomotor system. | Growth Disorders |
Thermoregulation keeps the normal body temperature of humans at approximately 37 degrees C. However, as a result of heat load - both endogenous and exogenous heat - it can occur that the body is unable to dissipate excess heat, leading to an increase in the core body temperature. This can result in various heat illnesses, ranging from mild, non-life-threatening conditions, such as heat rash, heat edema, heat cramps, heat syncope and exercise associated collapse to life-threatening conditions, namely exertional heatstroke and classic heatstroke. Exertional heatstroke is the result of strenuous exercise in a (relatively) hot environment, whereas classic heatstroke is caused by environmental heat. Both forms result in a core temperature of > 40 degrees C in combination with a lowered or altered consciousness. Early recognition and treatment are critical in reducing morbidity and mortality. Cornerstone of treatment is cooling. | Heat Stress Disorders |
The effects of almitrine (60 mg/24 h), raubasine (20 mg/24 h) and Duxil administered orally were compared in 30 elderly subjects (mean age: 60 years) who showed a decrease in oxygen saturation during maximum exercise. After 1 month of treatment, raubasine proved ineffective whereas almitrine and Duxil significantly reduced this decrease. The effect of Duxil was significantly more pronounced than that of almitrine. | Almitrine |
In LATS positive thyrotoxic patients the blood lymphocyte RNA content was significantly greater than normal, but not significantly different from normal in LATS negative thyrotoxicosis patients. Changes occurred in the RNA content of the lymphocytes following treatment whether by radioactive iodine or carbimazole." | Long-Acting Thyroid Stimulator |
The aging changes in human ciliary body were studied by histological analysis. Thirty four autopsy eyes were fixed in 2.5% formalin and 1.0% glutaraldehyde mixture. The age distribution was 12 eyes below 50 years of age 13 eyes between 60 and 70 years of age, and 9 eyes over 80 years of age. Serial sections of the ciliary body were made parallel to the limbus and vertical to the ciliary processes. From four areas (transitional portion between pars plana and pars plicata, posterior portion of pars plicata, middle portion of pars plicata, and anterior portion of pars plicata) a central section was selected. Histological analysis was done with the use of Azur II stained light microscopic pictures. The basement membrane of non-pigmented epithelium below 50 years of age was thinner than between 60 and 70 years of age. This finding may be related with lowering aqueous humor secretion with aging. Non-pigmented epithelium, blood vessels in the stroma, and muscle fibers in muscle tissue showed aging changes. The pigment epithelium, basement membrane, and muscle fibers in muscle tissue did not show aging changes in light microscopical analysis, but study of their fine structure is necessary. | Ciliary Body |
Large-scale genome-wide association studies have identified several susceptibility variants associated with the risk of primary open-angle glaucoma (POAG), among which rs4236601 (CAV1/CAV2) at chromosome 7q31 and rs2157719 at chromosome 9p21 (CDKN2B-AS1). The purpose of this study was to investigate whether these variants contribute to the incidence of POAG in a sample of the Brazilian Southeastern population and to determine the best-fitted genetic model for these single nucleotide polymorphisms (SNPs). A case-control study with 557 individuals, 310 with POAG, and 247 controls was conducted through PCR and direct sequencing. We observed a significant effect of the heterozygous genotype (G/A) of rs2157719 that occurred more frequently in the control group (p = 0.0004; OR: 0.517, CI 95%: 0.357-0.745). Allele frequencies also differed between cases and controls (p = 0.006; OR: 0.694, CI 95%: 0.522-0.922) with the best-fitted genetic model for rs2157719 being the codominant model. No differences were observed for genotype and allele distributions in relation to rs4236601 in the CAV1/CAV2 region. The association of rs2157719 (CDKN2B-AS1) with the POAG phenotype corroborates previously published results, reinforcing the importance of this variant in POAG etiology. | Caveolin 2 |
Hospitalized COVID-19 patients are vulnerable to different degrees of stress disorders as well as depression, anxiety and fear. The aim of this study was to evaluate the feasibility of introducing Music therapy on site with Covid-19 patients and investigating the immediate effects a single session has on anxiety, heart rate (HR), oxygen saturation (O2Sat) and satisfaction compared to standard care. A randomized controlled trial of 40 patients was conducted. Participants were assigned to control group (CG) or the treatment group (MG). MG received an individual single session of music therapy in presence. CG received standard care. MG and CG were subjected to identical measurements (pre-during-post) of the parameters STAI-Y, HR and O2Sat. Participants in MG were asked to fill in an optional open-ended question concerning their experience with music therapy. Significant difference in anxiety levels between scores in MG and CG (34.50 (23.25-40.00) vs 45.00(38, 25-54.00); p = 0.000) was observed. MG compared to CG had statistically significantly higher values of O2Sat (97.50 (96.25-99.00) versus 96.00 (96.00-98.00); p = 0.026). Results show the feasibility of introducing music therapy as a supporting complementary/non-pharmacological intervention on site in Covid-19 patients. A single session of music therapy improves O2Sat and can significantly reduce anxiety.Trial registration: 14/10/2021 No. NCT05077306. https://www.clinicaltrials.cov . | Sensory Art Therapies |
Pathogens are known to survive in compost and to regrow under the influence of certain factors, such as moisture content, temperature and nutrient availability. Dead biomass, by providing available nutrients, is a factor that may affect pathogen regrowth. However, the indigenous microorganisms, including pathogens, that grown on the dead biomass of compost have not yet been identified. Here, the regrowth potential of the pathogenic indicator bacterium Escherichia coli in the presence of dead bacterial biomass was determined, and the biomass metabolizers that grew competitively with E. coli were identified by high-sensitivity stable isotope probing of rRNA. Culture-dependent analysis indicated that the addition of dead bacterial biomass did not stimulate E. coli growth. High-throughput analysis of density-resolved 16S rRNA molecules from compost samples amended with carbon-13-labeled dead bacterial biomass revealed dead bacterial-assimilating bacteria, including Sphingobium sp., myxobacterial lineages and Bacillales. These bacteria are potentially competitive with pathogens due to their preferential assimilation of dead biomass in compost. | Carbon Isotopes |
A review about the different groups of oral contraceptives as monophasic combined pills, two-, triphasic and sequential preparations is given. Discussion of contraindications and advises for prescribing practice. | Contraceptives, Oral |
It is 16 years since we reviewed anhedonia in depression. Since then, there have been important developments in the study of anhedonia, mainly using the new techniques that neuroimaging made available, which provide very interesting new insights. It is becoming increasingly apparent that anhedonia, with psychomotor retardation, defines a dimension in depressive disorder that seems to be distinct from a dimension encompassing mood plus somatic symptoms. These dimensions can coexist, but may also be present separately. The first appears associated with disturbances (under-functioning) in dopamine function; the other appears to be related to a similar under-functioning in the serotonin system. Furthermore, anhedonia itself increasingly appears to be a composite symptom, consisting of at least two dimensions (i.e. a motivational/appetitive and a consummatory one). Depression appears to be characteristically linked more to the first one, in contrast to what was originally thought. We discuss the significance of the above in the evolving treatment of depression and the potential use of dopamine-targeting drugs. | Anhedonia |
This work provides new insights from our team regarding advances in targeting canonical and non-canonical nucleic acid structures. This modality of medical treatment is used as a form of molecular medicine specifically against the growth of cancer cells. Nevertheless, because of increasing concerns about bacterial antibiotic resistance, this medical strategy is also being explored in this field. Up to three strategies for the use of DNA as target have been studied in our research lines during the last few years: (1) the intercalation of phenanthroline derivatives with duplex DNA; (2) the interaction of metal complexes containing phenanthroline with G-quadruplexes; and (3) the activity of Mo polyoxometalates and other Mo-oxo species as artificial phosphoesterases to catalyze the hydrolysis of phosphoester bonds in DNA. We demonstrate some promising computational results concerning the favorable interaction of these small molecules with DNA that could correspond to cytotoxic effects against tumoral cells and microorganisms. Therefore, our results open the door for the pharmaceutical and medical applications of the compounds we propose. | Polyelectrolytes |
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