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Here, we describe a novel mycovirus, tentatively designated as Rhizoctonia solani fusarivirus 6" (RsFV6), which was discovered in Rhizoctonia solani AG-3 PT strain 3P-2-2. The virus has a single-stranded positive-sense RNA (+ssRNA) genome of 6141 nucleotides containing two open reading frames (ORFs) and a poly(A) tail. ORF1 encodes a large polypeptide of 1,862 amino acids (aa) with conserved RNA-dependent RNA polymerase (RdRp) and helicase (Hel) domains. ORF2 encodes a putative 167-aa protein of unknown function. BLASTp searches revealed that the ORF1-encoded polypeptide showed the highest sequence similarity (70.67% identity) to that of Rhizoctonia solani fusarivirus 3 (RsFV3), which was isolated from Rhizoctonia solani AG-2-2LP. Multiple sequence alignments and phylogenetic analysis based on RdRp and Hel sequences indicated that RsFV6 could be a novel member of the genus Alphafusarivirus family Fusariviridae." | Fungal Viruses |
[Figure: see text]. | Serine-Threonine Kinase 3 |
The grass carp (Ctenopharyngodon idella) aquaculture industry in Asia is prone to bacterial and viral hemorrhagic diseases. Effective adjuvants for vaccine formulation are the need of the hour for control of these diseases and long-term sustainability of grass carp farming. In this study, the involvement of interleukin-12 (IL-12) from grass carp (gcILâÂÂ12) in anti-bacterial and anti-viral immune responses was demonstrated via expression profiles of gcIL-12 subunits in immune tissues of the fish, following infection by Aeromonas hydrophila and Aquareovirus. Additionally, cDNA of the gcIL-12 subunits, p35 and p40 was cloned and characterized. We found that most of the structurally and functionally important features of vertebrate orthologues were conserved in gcIL-12 subunits, p35 and p40, with some features specific to grass carp. High levels of gcIL-12 p35 expression in the brain and gills suggest that IL-12 plays an important role in neural and immune systems. High expression levels in the heart, blood, and immune-related tissues suggest an important role in circulation and the immune system as well. Infections by both, A. hydrophila and Aquareovirus stimulated the mRNA expression of gcIL-12 subunits, p35 and p40 in most immune tissues. Significant upregulation or downregulation of gcIL-12 subunits, p35 and p40 by bacterial and viral infection confirms their potential role in anti-bacterial and anti-viral immune responses in fish. | Interleukin-12 Subunit p35 |
The osseointegration capability of titanium decreases over time. This phenomenon, defined as biological aging of titanium, is associated with the disappearance of hydrophilicity and the progressive accumulation of hydrocarbons on titanium surfaces. The objective of this study was to examine whether coating of titanium surfaces with 4-(2-Hydroxylethyl)-1-piperazineethanesulfonic acid (HEPES) buffer, a nonvolatile zwitterionic chemical buffering agent, could prevent the time-dependent degradation of the bioactivity of titanium. Commercially pure titanium samples, prepared as disks and cylinders, were acid-etched with H(2)SO(4). A third of the samples were used for experiments immediately after processing (new surfaces), while another third were stored under dark ambient conditions for 3 months (3-month-old surfaces). The remaining third were coated with HEPES after acid-etching and were stored for 3 months (HEPES-coated 3-month-old surfaces). The 3-month-old surfaces were hydrophobic, while new and HEPES-coated 3-month-old surfaces were superhydrophilic. Protein adsorption and the number of osteoblasts attached during an initial culture period were substantially lower for 3-month-old surfaces than for new and HEPES-coated 3-month-old surfaces. Alkaline phosphatase activity and calcium deposition in osteoblast cultures were reduced by more than 50% on 3-month-old surfaces compared to new surfaces, whereas such degradation was not found on HEPES-coated 3-month-old surfaces. The strength of in vivo bone-implant integration for 3-month-old implants, evaluated by the push-in test, was 60% lower than that for new implants. The push-in value of HEPES-coated 3-month-old implants was equivalent to that of new implants. Coating titanium surfaces with HEPES containing an antioxidant amino acid derivative, N-acetyl cysteine (NAC), further enhanced osteoblast attachment to the surfaces, along with the increase level of intracellular glutathione reserves as a result of cellular uptake of NAC. These results suggest that HEPES coating of titanium surfaces maintained their superhydrophilicity for at least 3 months and resulted in a continuous retention of bioactivity and osteoconductivity similar to freshly prepared surfaces. This coating technology may be useful for preventing biological aging of titanium and delivering biological molecules for synergistic enhancement of bone-titanium integration. | HEPES |
The microscopic explanation of the physical phenomena represented by a macroscopic theory is often cast in terms of the reduction of the latter to a more fundamental theory, which represents the same phenomena at the microscopic level, albeit in an idealized way. In particular, the reduction of thermodynamics to statistical mechanics is a much discussed case-study in philosophy of physics. Based on the Generalized Nagel-Schaffner model, the alleged reductive explanation would be accomplished if one finds a corrected version of classical thermodynamics that can be strictly derived from statistical mechanics. That is the sense in which, according to Callender (1999, 2001), one should not take thermodynamics too seriously. Arguably, the sought-after revision is given by statistical thermodynamics, intended as a macroscopic theory equipped with a probabilistic law of equilibrium fluctuations. The present paper aims to evaluate this proposal. The upshot is that, while statistical thermodynamics enables one to re-define equilibrium so as to agree with Boltzmann entropy, it does not provide a definitive solution to the problem of explaining macroscopic irreversibility from a microscopic point of view. | Entropy |
INTRODUCTION: The influenza vaccination is a priority during pregnancy due to infection-related-outcomes. The study aim is to assess the acceptance by women of influenza vaccination during pregnancy based on Health Belief Model (HBM). METHODS: A multicentre observational study was carried out with a convenience sample of 300 respondents. RESULTS: Most women (53.7%) declared that they worried to contract influenza during pregnancy and 80.7% of them agreed that there is a risk of contracting influenza during the first months of life. Vaccine benefits (adjOR 4.3 CI 95% 1.7-10.9 p <0.01), information on vaccination (adjOR 2.6 CI 95% 1.2-5.5 p <0.01) and trust in guidelines (adjOR 3.5 CI 95% 1.6-7.3 p <0.01) are some factors associated with intent/vaccination during pregnancy. CONCLUSIONS: HBM confirms its effectiveness in explaining/predicting health behaviours. It is necessary to create trust in the vaccinations through an integrated work of health professionals to set up training programs and to provide effective health communication. | Health Belief Model |
Lineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism of adaptive resistance to targeted therapy in cancer. An archetypal example is the development of neuroendocrine prostate cancer (NEPC) after treatment of prostate adenocarcinoma (PRAD) with inhibitors of androgen signaling. NEPC is an aggressive variant of prostate cancer that aberrantly expresses genes characteristic of neuroendocrine (NE) tissues and no longer depends on androgens. Here, we investigate the epigenomic basis of this resistance mechanism by profiling histone modifications in NEPC and PRAD patient-derived xenografts (PDXs) using chromatin immunoprecipitation and sequencing (ChIP-seq). We identify a vast network of cis-regulatory elements (N~15,000) that are recurrently activated in NEPC. The FOXA1 transcription factor (TF), which pioneers androgen receptor (AR) chromatin binding in the prostate epithelium, is reprogrammed to NE-specific regulatory elements in NEPC. Despite loss of dependence upon AR, NEPC maintains FOXA1 expression and requires FOXA1 for proliferation and expression of NE lineage-defining genes. Ectopic expression of the NE lineage TFs ASCL1 and NKX2-1 in PRAD cells reprograms FOXA1 to bind to NE regulatory elements and induces enhancer activity as evidenced by histone modifications at these sites. Our data establish the importance of FOXA1 in NEPC and provide a principled approach to identifying cancer dependencies through epigenomic profiling." | Hepatocyte Nuclear Factor 3-alpha |
A concern in the current trend toward more aggressive undermining in rhytidectomy and liposuction surgery has been the potential for damage to the marginal mandibular nerve. This study was undertaken in an attempt to clarify the exact peripheral pathway of the marginal mandibular nerve. A series of 22 fresh cadaver heads were studied bilaterally by gross dissection and histologic studies. It was found that dissection superficial to the platysma up to a point 2 cm lateral to the lower lip can be done safely. Medial to this point, dissection is hazardous and is not indicated because the marginal mandibular nerve becomes more superficial as it travels to innervate its effector muscles. Additionally, dissection in this area is technically difficult because of the tight adherence of the skin to the underlying muscles. This adherence generally permits only the formation of fine superficial rhytids that are best treated by chemical peel or dermabrasion. | Mandibular Nerve |
Pathology developing within the confines of the superior mediastinum may produce changes that appear quite subtle on conventional radiographs. The zone of contact of lung with the left superior mediastinum is represented radiographically as a series of interrelated pleural reflections. These reflections may be altered by mediastinal disease, and an understanding of this anatomy can facilitate detection of abnormalities. | Mediastinum |
Individuals occupying dominant and subordinate positions in social hierarchies exhibit divergent behaviours, physiology and neural functioning. Dominant animals express higher levels of dominance behaviours such as aggression, territorial defence and mate-guarding. Dominants also signal their status via auditory, visual or chemical cues. Moreover, dominant animals typically increase reproductive behaviours and show enhanced spatial and social cognition as well as elevated arousal. These biobehavioural changes increase energetic demands that are met via shifting both energy intake and metabolism and are supported by coordinated changes in physiological systems including the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes as well as altered gene expression and sensitivity of neural circuits that regulate these behaviours. Conversely, subordinate animals inhibit dominance and often reproductive behaviours and exhibit physiological changes adapted to socially stressful contexts. Phenotypic changes in both dominant and subordinate individuals may be beneficial in the short-term but lead to long-term challenges to health. Further, rapid changes in social ranks occur as dominant animals socially ascend or descend and are associated with dynamic modulations in the brain and periphery. In this paper, we provide a broad overview of how behavioural and phenotypic changes associated with social dominance and subordination are expressed in neural and physiological plasticity. This article is part of the theme issue 'The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies'. | Social Dominance |
The B.1.1.529 (Omicron) variant, first detected in November 2021, was responsible for a surge in U.S. infections with SARS-CoV-2, the virus that causes COVID-19, during December 2021-January 2022 (1). To investigate the effectiveness of prevention strategies in household settings, CDC partnered with four U.S. jurisdictions to describe Omicron household transmission during November 2021-February 2022. Persons with sequence-confirmed Omicron infection and their household contacts were interviewed. Omicron transmission occurred in 124 (67.8%) of 183 households. Among 431 household contacts, 227 were classified as having a case of COVID-19 (attack rate [AR] = 52.7%).(dagger) The ARs among household contacts of index patients who had received a COVID-19 booster dose, of fully vaccinated index patients who completed their COVID-19 primary series within the previous 5 months, and of unvaccinated index patients were 42.7% (47 of 110), 43.6% (17 of 39), and 63.9% (69 of 108), respectively. The AR was lower among household contacts of index patients who isolated (41.2%, 99 of 240) compared with those of index patients who did not isolate (67.5%, 112 of 166) (p-value <0.01). Similarly, the AR was lower among household contacts of index patients who ever wore a mask at home during their potentially infectious period (39.5%, 88 of 223) compared with those of index patients who never wore a mask at home (68.9%, 124 of 180) (p-value <0.01). Multicomponent COVID-19 prevention strategies, including up-to-date vaccination, isolation of infected persons, and mask use at home, are critical to reducing Omicron transmission in household settings. | Serial Infection Interval |
The present study evaluates the sensitivity of pharmacokinetic model output to variability in the biochemical and metabolic input parameters. Pharmacokinetic models of three chemicals are chosen for analysis: styrene, methylchloroform, and methylene chloride. Results show that model sensitivities are time-, dose-, and species-dependent and that the most sensitive parameters are the maximum Michaelis-Menten metabolism rate Vmax and the blood/air and fat/air partition coefficients. For humans, the muscle/air partition coefficient is also important. Model output is insensitive to the Michaelis-Menten parameter Km (except for low doses) and to other tissue/air partition coefficients. | Trichloroethanes |
Drug-facilitated sexual assaults (DFSA) currently represent overwhelming issue in its multidisciplinary approach. They occur when alcohol or drugs are used to compromise an individual's ability to consent to a sexual act. These substances facilitate a perpetrator to commit sexual assault because they inhibit a person's ability to resist and can prevent them from remembering the assault. If on the one hand alcohol remains the most commonly used drug in crimes of sexual assault, on the other hand drugs being used by perpetrators in crimes of sexual assault include, but are not limited to, Rohypnol (but also other benzodiazepines can be used), GHB (Gamma Hydroxybutyric Acid), GBL (Gamma-Butyrolactone), ketamine and others. The authors briefly examine the main issues of GHB-facilitated sexual assault in forensic investigation, drawing the attention of the whole scientific community to the importance of a correct assessment of each GHB-FSA, even when it is only suspected and by providing some practical advices. | Sodium Oxybate |
The imbalance of human gut microbiota has been associated with colorectal cancer. In recent years, metagenomics research has provided a large amount of scientific data enabling us to study the dedicated roles of gut microbes in the onset and progression of cancer. We removed unrelated and redundant features during feature selection by mutual information. We then trained a random forest classifier on a large metagenomics dataset of colorectal cancer patients and healthy people assembled from published reports and extracted and analysed the information from the learned decision trees. We identified key microbial species associated with colorectal cancers. These microbes included Porphyromonasasaccharolytica, Peptostreptococcusstomatis, Fusobacterium,Parvimonas sp., Streptococcusvestibularis and Flavonifractorplautii. We obtained the optimal splitting abundance thresholds for these species to distinguish between healthy and colorectal cancer samples. This extracted consensus decision tree may be applied to the diagnosis of colorectal cancers. | Fusobacterium |
Wilson disease is an autosomal recessive disorder in which copper pathologically accumulates primarily within the liver, brain and other tissues. It can presents clinically as liver disease, as a progressive neurological disorder or as psychiatric illness. The wide array of clinical manifestations of WD can lead to misdiagnosis with subsequent greater risk of irreversible damage to liver and brain. Many tests can be used to investigate patients of Wilson disease, including serum free copper, 24 hours urine copper estimation, hepatic copper estimation and genetic mutation testing. But there is no single ideal diagnostic test that can exclude or confirm the disease with certainty. The aim of the study was to find out the efficacy of different diagnostic test for the diagnosis of Wilson disease. This cross-sectional analytical study was conducted at department of Paediatric Gastroenterology and Nutrition of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from January 2016 through January 2018. A total of 56 cases of Wilson disease and 39 patients with a liver disease other than WD were studied. Wilson disease was diagnosed by Leipzig score. Along with other physical findings and laboratory investigations slit lamp eye examination for KF ring, serum ceruloplasmin and 24 hour urinary copper excretion were done. The mean age of WD patients was 9.69+/-2.37 years, male female ratio was 1:1. Serum ceruloplasmin level was significantly lower in WD patient (p<0.001). Median of 24 hour urinary copper in WD was 702.75mug/ 24 hr (range119-11210mug/24 hour) and in non WD group it was 77.41mug/24 hour (range 20.0-478mug/24 hour) and the difference between them is statistically significant (p=0.001). The sensitivity of KF ring was 82.1% and specificity was 100%. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of serum ceruloplasmin were 98.2%, 92.3%, 94.8%, 97.2% and 95.7% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 24 hour urinary copper were 100%, 63%, 80% and 85.1% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of KF ring, serum ceruloplasmin and basal 24 hour urinary copper excretion when combined together came out to be 70.4%, 100%, 100%, 59.3% and 79.3% respectively. This study result showed that serum ceruloplasmin and 24 hour urinary copper can be used as a screening test for the diagnosis of Wilson disease. | Ceruloplasmin |
This is the story of author's life from high school through retirement. The author took early retirement after 25 years of practice in a multispecialty clinic then founded a free clinic in Mexico that the author ran for 15 years. | Geraniaceae |
The author has previously shown that the addition of egg-white lysozyme to the reaction mixture used in the Treponema pallidum immobilization test (TPI test) can reduce the time required for immobilization from 18 hours to as little as 6 hours. This opened up the possibility of developing a one-day TPI test and of further simplifying the procedure, as the conditions do not need to be so strictly controlled to ensure survival of the treponemes for the shorter time. In this paper it is shown that the standard procedure of incubation under an atmosphere of nitrogen and carbon dioxide can be replaced by incubation under a layer of liquid paraffin. The survival of treponemes is satisfactory under these conditions and the oil technique does not alter the sensitivity of the 6-hour test with added lysozyme. Comparative tests using the standard procedure, the lysozyme-gas technique and the lysozyme-oil technique showed that both modifications give the same degree of sensitivity and specificity after incubation for 6 hours as does the standard method. The feasibility of introducing these modifications into routine laboratory practice is discussed. | Treponema Immobilization Test |
We present solid-state NMR measurements of beta-strand secondary structure and inter-strand organization within a 150-kDa oligomeric aggregate of the 42-residue variant of the Alzheimer's amyloid-beta peptide (Abeta(1-42)). We build upon our previous report of a beta-strand spanned by residues 30-42, which arranges into an antiparallel beta-sheet. New results presented here indicate that there is a second beta-strand formed by residues 11-24. Contrary to expectations, NMR data indicate that this second beta-strand is organized into a parallel beta-sheet despite the co-existence of an antiparallel beta-sheet in the same structure. In addition, the in-register parallel beta-sheet commonly observed for amyloid fibril structure does not apply to residues 11-24 in the 150-kDa oligomer. Rather, we present evidence for an inter-strand registry shift of three residues that likely alternate in direction between adjacent molecules along the beta-sheet. We corroborated this unexpected scheme for beta-strand organization using multiple two-dimensional NMR and (13)C-(13)C dipolar recoupling experiments. Our findings indicate a previously unknown assembly pathway and inspire a suggestion as to why this aggregate does not grow to larger sizes." | Protein Conformation, beta-Strand |
Previous studies of birth certificates have not fully evaluated how accurately they identify delivery methods that have a historical component, such as repeat cesarean and vaginal birth after previous cesarean (VBAC). The authors used linked Georgia birth certificates for first and second deliveries to examine the accuracy of four reported delivery methods in the second pregnancy: vaginal (without previous cesarean), VBAC, primary cesarean, and repeat cesarean, as well as an indicator of a previous cesarean. From the immediate birth certificates, the delivery method for each of the two births was classified as vaginal (V) or cesarean section (CS), which produced possible sequences of V-V, CS-V, V-CS, and CS-CS. The delivery method for the second births to 106,049 women from 1989 through 1992 was reviewed, taking into account the historical information from the linked certificates regarding the first births. Only 42.0% of women with a CS-V sequence were correctly designated on the second birth certificate as a VBAC; 79.3% of women with a V- CS sequence were correctly designated as primary cesarean. From 1980 through 1988, birth certificates contained a check box indicating a previous cesarean (but no VBAC box). During this period, only 75.5% of 25,491 women with a previous cesarean were so designated on the birth certificate. These findings suggest that cross-sectional vital records data substantially underestimate VBAC and primary cesarean rates. | Birth Certificates |
After recent sampling in the Southeast and Northeast of Brazil, six new species of Aphilodon are described and illustrated based on males and females. From the Atlantic Forest biome, Aphilodon foraminis n. sp., A. aiuruocae n. sp., A. acutus n. sp. and A. rectitibia n. sp. were registered in the state of Rio de Janeiro. Aphilodon cangaceiro n. sp. is the first record of Aphilodontinae for the state of Piau and was sampled in the Caatinga biome. Aphilodon bahianus n. sp. is the first species of Aphilodontinae known for the state of Bahia, being registered from the Atlantic Forest and in the Caatinga biomes. Additionally, some morphological characteristics of all known species of Aphilodon and their distributions are compared. | Chilopoda |
Although the measurement of intracranial pressure (ICP) is gaining widespread acceptance, the most desirable method of measurement is disputed. Subdural fluid-coupled techniques are associated with an increased risk of infection, and epidural techniques are associated with decreased accuracy. We investigated epidural measurement techniques and suggest that the necessary and sufficient criteria for accurate epidural measurement of ICP are adequate transducer size and stiffness, transducer-dura coplanarity, transducer-guard ring coplanarity, complete dural contact, and rigid fixation. An epidural transducer design was developed and prototypes were constructed using these principles. The transducer requires no percutaneous connections, fluid coupling, or batteries. Transducer accuracy was +/- 2.2 torr in bench stability studies lasting up to 198 days, +/- 3.0 torr in acute animal studies of less than 24 hours, and +/- 7.9 torr in chronic animal studies lasting up to 112 days. Error bounds are expressed such that 95% of individual measurements are expected to have error less than the bound; average error is one-third of the bound. Average transducer drift was 0.1 torr per day; our reported accuracy in chronic studies used drift correction from preimplantation data. We conclude that accurate measurement of ICP using an epidural transducer is feasible. | Manometry |
Ovarian adrenal rest tumors (OART) are tumors that develop in females with congenital adrenal hyperplasia (CAH). In contrast to their counterpart in testicles, they are exceptional and few cases have been reported in the literature. In this report, we present clinicopathological findings of a female patient with CAH due to 21-hydroxylase deficiency who was incidentally diagnosed with OART with a review of the literature. The 14-year-old patient, who was raised as a boy, developed a virilizing syndrome with high testosterone levels that were attributed to non adherence to her replacement corticosteroid therapy. She consulted for sex reassignment surgery. Pelvic ultrasound was normal. She underwent hysterectomy and bilateral adnexectomy. No abnormalities were noticed during the operation. Grossly, both ovaries were variegated with well circumscribed and lobulated, brownish-yellow nodules. Histologically, the nodules were composed of nests of large polygonal cells with centrally located nuclei and prominent nucleoli. There was mild atypia and no crystals of Reinke. Thus, the findings of the histopathological examination were consistent with bilateral OART. Histological differential diagnosis of OART can be challenging particularly with leydig cell tumor, stromal luteoma and steroid cell tumors, not otherwise specified. OART must be considered in women with CAH and persistent virilizing symptoms despite negative imaging results. | Adrenal Rest Tumor |
We report a patient with the unusual coincidence of two rare congenital disorders, lingual ectopy of the thyroid gland and resistance to thyroid hormone (RTH), resulting in impaired thyroid hormone production and action, respectively. The proposita had a positive thyrotropin (TSH) newborn screening test (350 mU/L, confirmed) with normal thyroxine (T4) and no clinical signs of hypothyroidism. A scintiscan revealed lingual but no orthotopic thyroid tissue. Levothyroxine (LT4) replacement failed to reduce TSH and was discontinued after four months owing to significantly elevated free T4. Her physical and mental development was unremarkable, and she was considered to be clinically euthyroid throughout childhood, even though she received either no T4 or a dose insufficient to lessen hyperthyrotropinemia. At the age of 15 years, T4 was gradually increased to a supraphysiological dose of 300 microg/d, resulting in the normalization of the serum TSH level, and subjective improvements in her ability to concentrate. The proposita's mother was clinically euthyroid, had a palpable diffuse goiter, and thyroid function tests consistent with RTH. This diagnosis was confirmed by detection of a heterozygous mutation (R320H) in the thyroid hormone receptor-beta (TR-beta) gene found in both the proposita and her mother. Under the high-dose T4 regimen, the patient's TSH and free T4 values resembled those of untreated patients with TRbeta R320H mutation, suggesting that a compensated state could be achieved, at least at the pituitary level. In the proposita, treatment of hyperthyrotropinemia is clearly mandatory because of potential complications inflicted by TSH-stimulated growth of the lingual tissue. To our knowledge, this represents the first report of congenital hypothyroidism secondary to thyroid dysgenesis complicated by coincidental RTH. | Lingual Goiter |
Paget's disease of bone is a focal disorder of bone remodelling that progresses slowly and leads to changes in the shape and size of affected bones and to skeletal, articular and vascular complications. In some parts of the world it is the second most common bone disorder after osteoporosis though in recent years its prevalence and severity appear to decrease. The disease is easily diagnosed and effectively treated but its pathogenesis remains incompletely understood. | Osteitis Deformans |
Nowadays, Ultrasound contrast agent (UCA) is not only a good contrast agent for ultrasonic imaging, but also an important tool for drug delivery. As a kind of UCA, lipofectamine has the shell with positive charge. It can encapsulate genes and also be adhered to cells because genes and cells are all with negative charge. With this feature, it plays an important role in transfection. Scavenger Receptor Class B Type I(SR-BI) is a HDL receptor thought to be the first step in the progress of cholesterol transport. In this way, SR-BI loaded UCA has great possibility to cure atherosclerosis plaque. | Scavenger Receptors, Class C |
The field of HIV medicine has changed rapidly in the last two decades since effective and tolerable antiretroviral treatment became available. As a result, although classical opportunistic infections of the brain have become less common, clinicians need to be aware of a wider range of acute and chronic complications of HIV and its treatment. In this article, we summarise major opportunistic infections, immune reconstitution inflammatory syndrome, HIV-associated neurocognitive disorders, and cerebrovascular disease in HIV positive patients. We also emphasise the preventability and reversibility of most of the central nervous system complications of HIV, and hence the importance of early diagnosis of HIV and involvement of clinicians with special expertise in HIV medicine. | Blood-Borne Infections |
Folate receptor family members (FOLRs) mediate the delivery of 5-methyltetrahydrofolate to the interior of, out of within, or between cells in a process known as potocytosis. Three FOLRs and a pseudogene map to 11q13.4. The aim of this study was to verify whether FOLRs could be responsible for the onset of nonsyndromic cleft lip with or without cleft palate (CL/P). Linkage and linkage disequilibrium between genetic markers and disorder were analyzed. Patients and their mothers from 71 familial CL/P pedigrees and 75 sporadic cases from Italian population were investigated by PCR-SSCP analysis. Data from mutation scanning allowed us to find only a silent mutation in FOLR1 present in a mother and her child. Our findings do not support FOLR1 and FOLR2 genes in the onset of CL/P." | Folate Receptors, GPI-Anchored |
Angiotensin II type 1 receptor (AT(1)R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT(1)R blockers (ARBs), the structural basis for AT(1)R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high-quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT(1)R in complex with its selective antagonist ZD7155 at 2.9-A resolution. The AT(1)R-ZD7155 complex structure revealed key structural features of AT(1)R and critical interactions for ZD7155 binding. Docking simulations of the clinically used ARBs into the AT(1)R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT(1)R structure-function relationship and structure-based drug design. | Receptor, Angiotensin, Type 1 |
Recognising an object involves rapid visual processing and activation of semantic knowledge about the object, but how visual processing activates and interacts with semantic representations remains unclear. Cognitive neuroscience research has shown that while visual processing involves posterior regions along the ventral stream, object meaning involves more anterior regions, especially perirhinal cortex. Here we investigate visuo-semantic processing by combining a deep neural network model of vision with an attractor network model of semantics, such that visual information maps onto object meanings represented as activation patterns across features. In the combined model, concept activation is driven by visual input and co-occurrence of semantic features, consistent with neurocognitive accounts. We tested the model's ability to explain fMRI data where participants named objects. Visual layers explained activation patterns in early visual cortex, whereas pattern-information in perirhinal cortex was best explained by later stages of the attractor network, when detailed semantic representations are activated. Posterior ventral temporal cortex was best explained by intermediate stages corresponding to initial semantic processing, when visual information has the greatest influence on the emerging semantic representation. These results provide proof of principle of how a mechanistic model of combined visuo-semantic processing can account for pattern-information in the ventral stream. | Perirhinal Cortex |
AIMS: The out-of-hospital cardiac arrest (OHCA) outcomes project is a national research registry. One of its aims is to explore sources of variation in OHCA survival outcomes. This study reports the development and validation of risk prediction models for return of spontaneous circulation (ROSC) at hospital handover and survival to hospital discharge. METHODS AND RESULTS: The study included OHCA patients who were treated during 2014 and 2015 by emergency medical services (EMS) from seven English National Health Service ambulance services. The 2014 data were used to identify important variables and to develop the risk prediction models, which were validated using the 2015 data. Model prediction was measured by area under the curve (AUC), Hosmer-Lemeshow test, Cox calibration regression, and Brier score. All analyses were conducted using mixed-effects logistic regression models. Important factors included age, gender, witness/bystander cardiopulmonary resuscitation (CPR) combined, aetiology, and initial rhythm. Interaction effects between witness/bystander CPR with gender, aetiology and initial rhythm and between aetiology and initial rhythm were significant in both models. The survival model achieved better discrimination and overall accuracy compared with the ROSC model (AUC = 0.86 vs. 0.67, Brier score = 0.072 vs. 0.194, respectively). Calibration tests showed over- and under-estimation for the ROSC and survival models, respectively. A sensitivity analysis individually assessing Index of Multiple Deprivation scores and location in the final models substantially improved overall accuracy with inconsistent impact on discrimination. CONCLUSION: Our risk prediction models identified and quantified important pre-EMS intervention factors determining survival outcomes in England. The survival model had excellent discrimination." | Out-of-Hospital Cardiac Arrest |
OBJECTIVE: The purpose of this study was to determine the potential usefulness of duplex sonography in the grading of portal hypertension. SUBJECTS AND METHODS: Duplex sonography of the portal vein system and measurement of the portal pressure and portosystemic pressure gradient were performed in 375 patients before placement of transjugular intrahepatic portosystemic shunts. Subgroups included patients with recent variceal bleeding (n = 296) and patients with refractory ascites without previous variceal bleeding (n = 79). A matched cohort of 100 patients without portal hypertension was also examined. Differences between the groups in portal and splenic vein diameter, flow velocity, congestion index, and hepatic arterial resistive index were assessed using the Wilcoxon rank sum test. RESULTS: Compared with healthy individuals, our patients had an increased portal vein diameter (+30%, p < .001), decreased portal vein flow velocity (-44%, p < .001), and increased congestion index (+185%, p < .001). A portal vein diameter greater than 1.25 cm or a portal vein flow velocity less than 21 cm/sec indicated portal hypertension with a sensitivity and specificity of 80%. If the congestion index exceeded 0.1, portal hypertension was diagnosed with a 95% sensitivity and specificity. The portal pressure and gradient correlated only weakly (r < .2, p < .05) with sonographic variables. Using multivariate analysis, subgroups with variceal bleeding or refractory ascites did not show differences in hemodynamics, including pressures. CONCLUSION: Duplex sonography contributes to the diagnosis of portal hypertension but does not allow its grading. Similarity of portal hemodynamics between patients with variceal bleeding and patients with refractory ascites suggests that additional factors determine the respective clinical presentation. | Portal Pressure |
Gene regulatory networks developed from full genome expression libraries from gene perturbation variant cell lines can be used to quickly and efficiently identify the molecular mechanism of action of drugs or lead compound molecules. We developed an extensive yeast gene expression library consisting of full-genome cDNA array data for over 500 yeast strains each with a single gene disruption. Using this data, combined with dose and time course expression experiments with the oral antifungal agent, we used Boolean network discovery techniques to determine the genes whose expression was most profoundly affected by this drug. Our system identified the gene as the most significantly suppressed target molecule due to exposure to the antifungal agent. This process for network based drug discovery can significantly decrease the time and resources necessary to make rational drug targeting decisions. | Genomic Library |
Endodontic surgery aims at the resolution of a periapical inflammatory process by surgical access followed by enucleation of the lesion and root-end filling to curb any potentially noxious agent within the physical confines of the affected root. Guided bone regeneration could be associated to endodontic surgery aiming to enhance periradicular tissue regeneration. The objective of this paper was to review the scientific literature about guided bone regeneration in endodontic surgery, evaluating the effects on periapical lesion healing process. The included articles are classified considering the anatomical characteristics of the lesion. Fourteen articles were included in the review after abstract and title selection. Eight articles were on studies on lesions affecting only the periapical region (three about through-and-through lesions) while six were about the treatment of apico-marginal lesions. On the basis of the currently available literature, there is a low scientific evidence of a benefit related. to the use of guided bone regeneration procedure in endodontic surgery." | Guided Tissue Regeneration, Periodontal |
INTRODUCTION: The prevalence of diabetes and its complications in the Innu community of Sheshatshiu is high. We wanted to determine if shared medical appointments (SMAs) could provide culturally appropriate, effective treatment to Innu patients with relatively well-controlled diabetes, as an alternative to standard, 'one-on-one' care. METHODS: We conducted a mixed-method study including a randomised controlled trial comparing standard care versus SMAs for patients aged 18-65 years with haemoglobin A1C (HbA1C) of </=7.5%, followed by a qualitative study using semi-structured interviews with patients who attended SMAs. RESULTS: Among 23 patients, 13 received the intervention. There were no significant differences of HbA1C level or HbA1C percentage of change between intervention and control groups at baseline, 6 months or 12 months. There were no statistical differences between standard care and SMA groups, concerning mortality or the need for haemodialysis. The qualitative analysis found that patients generally enjoyed the SMA model and the peer support and learning benefits of the SMAs. Patients did not believe that the SMA model was more or less culturally appropriate than standard care, but the majority said they felt that the SMAs were good for the community and could be a good venue for incorporating Innu healthy-lifestyle knowledge into medical diabetes care. CONCLUSIONS: SMAs may be an efficient way to manage well-controlled diabetic patients in the Innu community of Sheshatshiu and to provide peer support and opportunities for learning and incorporating community-specific knowledge into care. | Shared Medical Appointments |
Angiogenesis, the process through which new blood vessels arise from pre-existing ones, is regulated by numerous classic" factors and other "nonclassic" regulators of angiogenesis. Among these latter urotensin-II is a cyclic 11-amino acid (human) or 15-amino acid (rodent) peptide, originally isolated from the fish urophysis, which exerts a potent systemic vasoconstrictor and hypertensive effect. This review article summarizes the literature data concerning the involvement of urotensin-II in angiogenesis." | Urotensins |
BACKGROUND: Crossed cerebellar diaschisis (CCD) refers to depressions in perfusion and metabolism within the cerebellar hemisphere contralateral to supratentorial disease. Prior investigation into CCD in cerebrovascular reactivity (CVR) has been limited to terminal CVR estimations (CVR(end) ). We recently have demonstrated the presence of unsustained CVR maxima (CVR(max) ) using dynamic CVR analysis, offering a fully dynamic characterization of CVR to hemodynamic stimuli. PURPOSE: To investigate CCD in CVR(max) from dynamic blood oxygen level-dependent (BOLD) MRI, by comparison with conventional CVR(end) estimation. STUDY TYPE: Retrospective. POPULATION: A total of 23 patients (median age: 51 years, 10 females) with unilateral chronic steno-occlusive cerebrovascular disease, without prior knowledge of CCD status. FIELD STRENGTH/SEQUENCE: A 3-T, T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) and acetazolamide-augmented BOLD imaging performed with a gradient-echo echo-planar imaging (EPI) sequence. ASSESSMENT: A custom denoising pipeline was used to generate BOLD-CVR time signals. CVR(end) was established using the last minute of the BOLD response relative to the first-minute baseline. Following classification of healthy versus diseased cerebral hemispheres, CVR(max) and CVR(end) were calculated for bilateral cerebral and cerebellar hemispheres. Three independent observers evaluated all data for the presence of CCD. STATISTICAL TESTS: Pearson correlations for comparing CVR across hemispheres, two-proportion Z-tests for comparing CCD prevalence, and Wilcoxon signed-rank tests for comparing median CVR. The level of statistical significance was set at P </= 0.05. RESULTS: CCD-related changes were observed on both CVR(end) and CVR(max) maps, with all CCD+ cases identifiable by inspection of either map. Diseased cerebral and contralateral cerebellar hemispheric CVR correlations in CCD+ patients were stronger when using CVR(end) (r = 0.728) as compared to CVR(max) (r = 0.676). CVR correlations between healthy cerebral hemispheres and contralateral cerebellar hemispheres were stronger for CVR(max) (r = 0.739) than for CVR(end) (r = 0.705). DATA CONCLUSION: CCD-related alterations could be observed in CVR examinations. Conventional CVR(end) may underestimate CVR and could exaggerate CCD. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 3. | Diaschisis |
We propose an object recognition architecture relying on a neural network algorithm in optical sensors. Precisely, by applying the high-speed and low-power Fourier transform operation in the optical domain, we can transfer the high-cost part of the traditional convolutional neural network algorithm to the sensor side to achieve faster computing speed. An optical neuron unit (ONU) consisting of transition metal sulfide (TMD) material is fabricated for a vivid validation of this architecture. Using the embedded gate pair structure inside our ONU, TMD materials can be electrically doped at different levels, forming an in-plane PN junction, which allows for effective manipulation of light response to imitate biological nerve synapses. The results demonstrate that our ONU could reach the ability of optic neurons, providing experimental support for future in-sensor computing architecture. | Fourier Analysis |
Purpose Transdifferentiation exists within stromal cells in the tumour microenvironment. Transforming growth factor-beta (TGF-beta) secreted by tumour-associated fibroblasts (TAFs) affects the differentiation states of epithelial cells, including epithelial-mesenchymal transition (EMT). Evodiamine, a natural drug, can regulate differentiation. However, the specific effects and relative mechanisms of evodiamine remain unknown. Design We used four models to observe the influence of TAF-like CCD-18Co cells on the colon epithelial cell line HCoEpiC: the 3D- and 2D-mono-culture system, Transwell and direct co-culture model. Additionally, we established conditioned medium from CCD-18Co cells. The TGF-beta pathway inhibitor LY364947 and evodiamine were added. Morphological changes and classical EMT markers were observed and detected using phase contrast microscopy and immunofluorescence. Cell migration was measured by the wound-healing assay. Western blotting was performed to detect the TGF-beta/Smad signalling pathway. Results CCD-18Co cells induced EMT-like changes in the 2D- and 3D-cultured epithelial cell line HCoEpiC, accompanied by high expression of ZEB1 and Snail and the enhancement of migration. Moreover, CCD-18Co-derived conditioned medium caused dysfunction of TGF-beta/Smad signalling in EMT. Evodiamine inhibited these EMT-like HCoEpiC and their migration. Additionally, evodiamine down-regulated the expression of ZEB1/Snail and up-regulated the expression of phosphorylated Smad2/3 (pSmad2/3). Evodiamine also increased the ratios of pSmad2/Smad2 and pSmad3/Smad3. Conclusion Based on our observations, evodiamine can reverse the TAF-induced EMT-like phenotype in colon epithelial cells, which may be associated with its mediation of phosphorylated Smad2 and Smad3 expression." | Smad Proteins, Receptor-Regulated |
An electromyographic technique was used to study the changes in postprandial motility induced by jejunal and ileal resection and jejunal bypass (50% reduction of total length of small bowel). Electrodes were implanted in rats throughout the intestine. Compared to control animals, the duration of postprandial interruption of the myoelectric complex (DIMC) was rapidly increased after jejunal resection, more gradually augmented after jejunal bypass, and remained constant after ileal resection. The frequency of occurrence of spike bursts during the postprandial period was significantly decreased in the short remaining proximal segment after jejunal resection and was not changed in the ileum. The jejunal bypass induced no change in the frequency throughout the remaining bowel. Ileal resection was followed by a decrease on the jejunum. The percentage of slow waves superimposed by a spike burst remained constant after jejunal resection and bypass but was significantly decreased after ileal resection on the whole remaining intestine. These results show important modifications in postprandial motor activity of the small bowel, which appear rapidly after jejunal resection, more gradually after jejunal bypass, and which are less pronounced after ileal resection. This electromyographic study emphasizes the role of intestinal motility in the development of adaptation after small bowel resection or bypass. | Jejunoileal Bypass |
Defensive microbes are of great interest for their roles in arthropod health, disease transmission, and biocontrol efforts. Obligate bacterial passengers of arthropods, such as Spiroplasma, confer protection against the natural enemies of their hosts to improve their own fitness. Although known for less than a decade, Spiroplasma's defensive reach extends to diverse parasites, both microbial and multicellular. We provide an overview of known defensive phenotypes against nematodes, parasitoid wasps, and fungi, and highlight recent studies supporting the role of Spiroplasma-encoded ribosome-inactivating proteins in protection. With cellular features well-suited for life in the hemolymph, broad distribution among invertebrate hosts, and the capacity to repeatedly evolve vertical transmission, Spiroplasma may be uniquely equipped to form intimate, defensive associations to combat extracellular parasites. Along with insights into defensive mechanisms, recent significant advances have been made in male-killing - a phenotype with interesting evolutionary ties to defense. Finally, we look forward to an exciting decade using the genetic tools of Drosophila, and the rapidly-advancing tractability of Spiroplasma itself, to better understand mechanisms and evolution in defensive symbiosis. | Spiroplasmataceae |
These studies were designed to compare intravenous and topical 16,16-dimethyl prostaglandin E2 (dmPGE2) as stimulants of gastric mucosal HCO3- secretion. In six Heidenhain pouch (HP) dogs, basal acid secretion was inhibited by cimetidine. With 100 ml 0.15 M NaCl as the fluid circulating through the HP, intrapouch titration to pH 6.0 was performed with 0.5 M HCl as titrant. After measuring basal HCO-3 secretion for 30 min, dmPGE2 was given intravenously or the fluid circulating in the HP was replaced by one containing dmPGE2. Intravenous dmPGE2 at infusion rates of 0, 0.5, 1.0, and 2.0 microgram . kg-1 . h-1 produced alkaline secretion rates of 34 +/- 9, 52 +/- 20, 72 +/- 21, and 70 +/- 20 (SE) mu mol . h-1, respectively. Topical dmPGE2 at concentrations of 0, 0.05, 1.25, and 2.50 microgram . ml-1 produced alkaline secretion rates of 22 +/- 7, 74 +/- 16, 134 +/- 28, and 144 +/- 35 mu mol . h-1, respectively (P less than 0,05 for each concentration). Glucosamine output, as an index of mucus secretion, increased significantly with HCO-3 secretion. We conclude that intragastric titration is a valid method for recording HCO-3 secretion from an HP, that topical dmPGE2 stimulates HCO3- secretion more effectively than intravenous dmPGE2, and that topical dmPGE2 stimulates mucus secretion as well as HCO-3 secretion, | Prostaglandins E, Synthetic |
By limiting stereopsis to measuring the distance of moving objects against a stationary background, insects can employ simple stratagems for solving the problems of stereoscopic range finding. | Appetitive Behavior |
Ribosomal protein L7/L12 is associated with translation initiation, elongation, and termination by the 70S ribosome. The guanosine 5' triphosphate hydrolase (GTPase) activity of elongation factor G (EF-G) requires the presence of L7/L12, which is critical for ribosomal translocation. Here, we have developed new methods for the complete depletion of L7/L12 from Escherichia coli 70S ribosomes to analyze the effect of L7/L12 on the activities of the GTPase factors EF-G, RF3, IF2, and LepA. Upon removal of L7/L12 from ribosomes, the GTPase activities of EF-G, RF3, and IF2 decreased to basal levels, while the activity of LepA decreased marginally. Upon reconstitution of ribosomes with recombinant L12, the GTPase activities of all GTPases returned to full activity. Moreover, ribosome binding assays indicated that EF-G, RF3, and IF2 require L7/L12 for stable binding in the GTP state, and LepA retained > 50% binding. Lastly, an EF-GâÂÂG' truncation mutant possessed ribosome-dependent GTPase activity, which was insensitive to L7/L12. Our results indicate that L7/L12 is required for stable binding of ribosome-dependent GTPases that harbor direct interactions to the L7/L12 C-terminal domains, either through a G' domain (EF-G, RF3) or a unique N-terminal domain (IF2). Furthermore, we hypothesize this interaction is concomitant with counterclockwise ribosomal intersubunit rotation, which is required for translocation, initiation, and post-termination. | Ribosomal Proteins |
This is a short introductory note to the texts of lectures presented at a Royal Society Discussion meeting held on 14-15 February 2005 and now published in this issue of Philosophical Transactions A. It contains a brief resume of the papers in the order they were presented at the meeting. This issue contains the texts of all of the presentations except those of Christophe Salomon, on cold atom clocks and tests of fundamental theory, and Francis Everitt, on Gravity Probe B, which were, unfortunately, not available. | International System of Units |
Gastrointestinal endoscopy including colonoscopy, esophagogastroduodenoscopy, and endoscopic retrograde cholangiopancreatography (ERCP) are safe and efficacious in elderly patients. Screening colonoscopies have little efficacy in patients over 80 years. Colonoscopies performed for bleeding or iron-deficiency anemia have a higher yield in elderly patients. Colonic preparations were well tolerated and colonoscopic success rates are high in elderly patients. However, poor colonic preparation is more likely in these patients. Esophagogastroduodenoscopy is a high-yield procedure with no significant increase in adverse events in patients over 80 years with symptoms including dyspepsia and dysphagia. ERCP in the elderly carries a high degree of success with low complication rates. Elderly patients undergoing ERCP carry similar risks of bleeding and perforation and a lower risk of pancreatitis compared with younger patients. Advanced age should not be regarded as an absolute contraindication to any gastrointestinal endoscopy procedure. | Endoscopy, Digestive System |
As a commonly used phthalate compound, di(n-butyl) phthalate (DBP) is an emerging group of polyvinyl chloride plasticizers. The acute toxicity of DBP has been extensively studied using the aquatic indicator organism, Daphnia magna. However, little is known about chronic and transgenerational toxicity of DBP. In this study, acute LC(50) values were 3.04 mg/L (24 h) and 2.55 mg/L (48 h). Chronic toxicity tests in the case of maternal exposure to DBP revealed that DBP had negligible effects on growth and reproduction of F3 generation of D. magna, although the growth rate of body length and the intrinsic rate of increase were prominently reduced, to a pretty small extent. At specific concentrations, DBP generated beneficial effects on the parental generation of D. magna and no obvious impacts on the F1 generation. This study showed that maternal exposure to DBP did not cause any transgenerational effects on D. magna. | Daphnia |
Pseudomonas fluorescens FD6 has been shown to possess many beneficial traits involved in the biocontrol of fungal plant pathogens, such as Botrytis cinerea and Monilinia fructicola. Vfr (virulence factor regulator) a highly conserved global regulator of gram-negative bacteria, such as the human pathogen Pseudomonas aeruginosa, is required for the expression of many important virulence traits. The role of Vfr in the regulation of biocontrol traits, such as the production of antibiotics to control fungal pathogens by antagonistic bacteria, has not been elucidated. This study investigated the effect of a vfr mutant derived from P. fluorescens FD6 to better understand the regulation of some important biocontrol traits associated with the bacterium. Biochemical studies indicated that the production of the antibiotics 2,4-diacetylphloroglucinol, pyrrolnitrin and pyoluteorin, was markedly enhanced in the vfr mutant. The vfr mutation also increased biofilm production, swimming motility and the expression of exopolysaccharide-associated gene (pelA, pslA and pslB) transcripts, but reduced protease production. Wheat rhizosphere and root tip colonization by the vfr mutant was higher than that by the wild type at 7 and 21days after inoculation. These findings demonstrate that Vfr modulates the expression of several key traits and the production of important antibiotics involved in the biocontrol potential of P. fluorescens FD6. | Pyrrolnitrin |
The Arf GTPase-activating protein ArfGAP1 and its brain-specific isoform ArfGAP1B play an important role in neurotransmission. Here we analyzed the distribution of ArfGAP1 in the mouse brain. We found high levels of ArfGAP1 in the mouse dentate gyrus where it displayed especially elevated level in the polymorph layer (hilus). Importantly, the ArfGAP1 signal follows the pathway of the granular cell axons so-called mossy fibers which extend from the dentate gyrus to CA3 via stratum lucidum and partially stratum oriens. Additionally, we identified differential expression of ArfGAP1 in the isocortex. Thus, staining with anti-ArfGAP1 antibodies allows distinction between cortical cell layers 1, 2, 3 and 5 from 4 and 6. Taken together, our data suggest that ArfGAP1 can be used as a specific marker of the dentate mossy fibers and as for visualization of cortical layers in immunohistochemical studies. | Mossy Fibers, Hippocampal |
Obesity and its associated metabolic disorders has become a major obstacle in improving the average life span. In this regard therapeutic approach using natural compounds are currently receiving much attention. Herbal compounds rich in triterpenes are well known to regulate glucose and lipid metabolism. Here, we have found that Ulmus pumila (UP) contained at least four different triterpenoids and inhibited adipogenesis of 3T3-L1 cells. The cell viability was dose dependently decreased by UP showing the increase of cell accumulation in G1 phase while reducing in S and G2/M phase of cell cycle. UP treatment also significantly decreased the GPDH activity and intracellular lipid accumulation. In addition, UP inhibited the mRNA levels of adipogenic transcription factors and lipogenic genes such as PPARgamma, C/EBPalpha, SREBP1c and FAS while showing no effects on C/EBP-beta and C/EBP-delta. Importantly enough, treatment of cells with UP suppressed the TNF-alpha induced activation of NF-kappaB signaling. Collectively, our results indicate that UP extract effectively attenuated adipogenesis by controlling cell cycle progression and down regulating adipogenic gene expression. | Ulmus |
In the growing field of plant systems biology, there is an undisputed need for methods allowing accurate quantitation of proteins and metabolites. As autotrophic organisms, plants can easily metabolize different nitrogen isotopes, resulting in proteins and metabolites with distinct molecular mass that can be separated on a mass spectrometer. In comparative quantitative experiments, treated and untreated samples are differentially labeled by nitrogen isotopes and jointly processed, thereby minimizing sample-to-sample variation. In recent years, heavy nitrogen labeling has become a widely used strategy in quantitative proteomics and novel approaches have been developed for metabolite identification. Here, we present an overview of currently used experimental strategies in heavy nitrogen labeling in plants and provide background on the history and function of this quantitation technique. | Nitrogen Isotopes |
Excavations at the 17th century site of Ferryland during the past 2 summers have revealed thousands of artifacts and the remains of several structures. Of particular interest here was the discovery of the remains of a privy and associated stable. Examination of privy contents revealed the presence of eggs of 4 parasites: Ascaris, Trichuris, Taenia, and Dicrocoelium. Their identification represents the first reported discovery of parasite remains in an archeological context in Canada. Due to possible contamination by domestic animal feces, it was not possible to determine with certainty if the eggs are of human origin. | Dicrocoeliasis |
BACKGROUND AND AIMS: Glycogen storage disease type Ib (GSD1b) is a rare metabolic and immune disorder caused by a deficiency in the glucose-6-phosphate transporter (G6PT) and characterized by impaired glucose homeostasis, myeloid dysfunction, and long-term risk of hepatocellular adenomas. Despite maximal therapy, based on a strict diet and on granulocyte colony-stimulating factor treatment, long-term severe complications still develop. Understanding the pathophysiology of GSD1b is a prerequisite to develop new therapeutic strategies and depends on the availability of animal models. The G6PT-KO mouse mimics the human disease but is very fragile and rarely survives weaning. We generated a conditional G6PT-deficient mouse as an alternative model for studying the long-term pathophysiology of the disease. We utilized this conditional mouse to develop an inducible G6PT-KO model to allow temporally regulated G6PT deletion by the administration of tamoxifen (TM). METHODS: We generated a conditional G6PT-deficient mouse utilizing the CRElox strategy. Histology, histochemistry, and phenotype analyses were performed at different times after TM-induced G6PT inactivation. Neutrophils and monocytes were isolated and analyzed for functional activity with standard techniques. RESULTS: The G6PT-inducible KO mice display the expected disturbances of G6P metabolism and myeloid dysfunctions of the human disorder, even though with a milder intensity. CONCLUSIONS: TM-induced inactivation of G6PT in these mice leads to a phenotype which mimics that of human GSD1b patients. The conditional mice we have generated represent an excellent tool to study the tissue-specific role of the G6PT gene and the mechanism of long-term complications in GSD1b." | Glycogen Storage Disease Type I |
Unlike other reviews written on this topic, the focus of this article is primarily on nonpharmacologic treatments for daytime sleepiness that is not secondary to other medical or psychological conditions. To provide an appropriate background on primary excessive daytime sleepiness, what is considered optimal sleep in terms of sleep duration, sleep insufficiency, and sleep need is discussed in detail. This discussion is followed by an examination of the behavioral strategy of banking sleep. After briefly discussing behavioral interventions for sleepiness associated with narcolepsy, a new behavioral method of treating daytime somnolence is proposed and described. | Sleepiness |
Seventy-six individuals of the European mudminnow Umbra krameri from two recent populations from Serbia (Bakreni Batar and Lugomir) and one from Bosnia and Herzegovina (Gromizelj) were analysed for habitat preferences and population structure. The population from Lugomir is a newly recorded population in Serbia. Besides this new record, it is noteworthy that all three studied locations are outside the currently known species distribution range limits. | Umbridae |
The Notch receptor and its ligands are key components in a core metazoan signaling pathway that regulates the spatial patterning, timing and outcome of many cell-fate decisions. Ligands contain a disulfide-rich Delta/Serrate/LAG-2 (DSL) domain required for Notch trans-activation or cis-inhibition. Here we report the X-ray structure of a receptor binding region of a Notch ligand, the DSL-EGF3 domains of human Jagged-1 (J-1(DSL-EGF3)). The structure reveals a highly conserved face of the DSL domain, and we show, by functional analysis of Drosophila melanogster ligand mutants, that this surface is required for both cis- and trans-regulatory interactions with Notch. We also identify, using NMR, a surface of Notch-1 involved in J-1(DSL-EGF3) binding. Our data imply that cis- and trans-regulation may occur through the formation of structurally distinct complexes that, unexpectedly, involve the same surfaces on both ligand and receptor. | Serrate-Jagged Proteins |
Vulvovaginal candidosis is increasing in incidence in many developed countries. Although for many women the sporadic occurrence of symptomatic episodes causes no more than temporary inconvenience and discomfort, in others the chronic or recurrent pattern of symptoms can be very distressing and disabling. Knowledge of the pathogenesis, predisposing factors and clinical features, although still incomplete, permits improved individual patient management and more appropriate use of specific antifungal therapy. Topical treatment with either polyenes or imidazoles gives short term mycological cure rates greater than 90%, but subsequent recolonization of the vagina and symptomatic relapse is common. Azole drugs offer the possibility of oral treatment which has increased patient acceptability; in particular, fluconazole, in a single dosage of 150 mg, is effective, well tolerated and safe. In chronic or recurrent disease, when underlying and predisposing conditions have been excluded, intermittent prophylaxis (topical or oral) may reduce the frequency of acute symptomatic episodes. | Candidiasis, Vulvovaginal |
In accordance with Recommendation 30b of the International Code of Nomenclature of Bacteria, which calls for the development of recommended minimal standards for describing new species, we propose minimal standards for describing the genus Mycobacterium and new slowly growing species of this genus. The minimal standards for assignment of a strain to the genus Mycobacterium include acid-alcohol fastness, a DNA G+C content in the range from 61 to 71 mol%, and mycolic acid detection with characterization of C22 to C26 pyrolysis esters. The recommended minimal standards for describing a new slowly growing Mycobacterium species are based on the results of phenotypic and genomic studies and include the results of the following conventional tests: growth at 25, 30, 33, 37, 42, and 45 degrees C; pigmentation; resistance to isoniazid, thiophene-2-carboxylic acid hydrazide, hydroxylamine, p-nitrobenzoic acid, sodium chloride, thiacetazone, picrate, and oleate; catalase activity; Tween hydrolysis; urease activity; niacin detection; and nitrate reductase, acid phosphatase, arylsulfatase, pyrazinamidase, and alpha-esterase activities. In addition, a mycolic acid profile should be determined, and DNA-DNA hybridization experiments in which the difference between the denaturation temperature of the homologous reaction and the denaturation temperature of the heterologous reaction is determined should be performed. This proposal has been endorsed by the members of the Subcommittee for Taxonomy of the Mycobacteria of the International Committee on Systematic Bacteriology. | Mycolic Acids |
Embryoscopy is the examination of the embryo at 9-10 weeks' gestation through the intact membranes by introducing an endoscope into the exocoelomic space transcervically or transabdominally. This is likely to remain confined to the management of early pregnancy in selected families affected by recurrent genetic syndromes with recognizable external fetal abnormalities. The procedure-related risk of fetal loss is around 12 per cent. Fetoscopy is the examination of the fetus after 11 weeks' gestation. This is performed transabdominally in the amniotic fluid. The technique has evolved with the miniaturization of the optical device by using fibre-optics technology. This procedure is likely to find new applications with the development of ultrasound examination at 10-14 weeks' gestation in order to, either confirm, or rule out suspected external fetal abnormalities. Amniocentesis can be performed at the same time. The procedure-related risk is likely to remain below 10 per cent but no accurate figures can be drawn from the literature." | Diagnostic Techniques, Obstetrical and Gynecological |
Contemplative traditions have long affirmed that compassion and kindness are trainable skills. While research on meditation practice has recently flourished, the mechanisms that might engender such changes are still poorly understood. Here, we present a motivational framework to explain why meditation training should increase concern for others and modulate empathic engagement with human suffering over time. Meditation practices are conceived as tools for enacting cognitive and emotion regulatory goals that are conditioned by the underlying ethical motivation of the training-to reduce and alleviate suffering. In support of this account, we present data from a randomized, wait-list-controlled study of intensive meditation. In Study 1, we use a novel cardiovascular index to show that 3 months of meditation training can increase the motivational salience of others' suffering, as compared to the salience of threats to oneself. In Study 2, we demonstrate that training-related changes in the ability to orient attention to suffering are mediated by the dynamic regulation of distress-related physiological arousal. Finally, in Study 3, we provide exploratory evidence suggesting that meditation training may influence how human suffering is encoded in memory, leaving lasting imprints on the recollection of emotional experience. Together, our findings suggest that meditation training can strengthen the motivational relevance of others' suffering, prompting a shift from self-focused to other-focused evaluative processing. Considering meditation training from a motivational standpoint offers an important perspective for understanding how compassion can be cultivated through intentional practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved). | Meditation |
A wide variety of chemicals discharged from industrial and municipal sources have been reported to disrupt the endocrine system of animals, which may be exposed via the food chain and contaminated water. 17alpha-Ethinylestradiol (EE(2)), a drug used in oral contraceptives and hormone replacement therapy, has a widespread presence in the aquatic environment. Current knowledge on the sensitivity of marine fish to estrogenic environmental chemicals is limited. We report here the effects of dietary intake of EE(2) on gilthead seabream, a marine hermaphrodite teleost, focusing on the immune events that take place in the gonad. When seabream males were fed with 5, 50, 125 and 200mug EE(2)/g food for 7, 14, 21 and 28days an infiltration of acidophilic granulocytes and B lymphocytes occurred in the testis as the same time that spermatogenesis is disrupted. Moreover, the dietary intake of EE(2) promoted a dose-dependent up-regulation of the expression of genes coding for cytokines, chemokines and adhesion molecules correlated with a leukocyte infiltration. | Hermaphroditic Organisms |
Thirteen complementary DNA (cDNA) probes were used to detect the presence of foot-and-mouth disease virus (FMDV) RNA extracted from cell cultures. When labelled with 32P, these probes enabled the detection of 1 pg of FMDV-RNA, or 1 virus copy per cell. Two FMDV A12 probes that coded for the leader, structural protein VP1 region and part of the polymerase gene respectively, showed no hybridization with other closely related picornaviruses. Differentiation between FMDV serotypes A, O and C was possible, using cDNA probes from individual serotypes that corresponded to structural protein VP1. | Aphthovirus |
The proposal that the stable expression of organogenesis-directing plasma membrane antigens, such as testis-organizing H-Y antigen, requires beta2-microglobulin-MHC antigen dimers as anchorage sites was tested on Daudi human Burkitt lymphoma cells [46, XY, 15q-, 14q+, beta2-m(-), HLA(-)]. The H-Y antigen level of Daudi was only 20% of that of Raji and Ramos, two human male pseudodiploid Burkitt lymphoma lines that were beta2-m(+), HLA(+). When Daudi is hybridized with beta2-m(+), HLA(+) cell lines, beta2-microglobulin, supplied by the latter, is known to restore the expression of Daudi HLA antigens A10 and BW17. Such restoration of HLA antigen expression markedly elevated H-Y antigen levels in those somatic hybrids. Thus the H-Y antigen level of the Daudi x Raji 8A (male X male) hybrid became equal to that of TetraRaji--the colcemide-induced Raji tetraploid line. Two independently derived Daudi x Hela D98 (male x female) hybrids, DAD 1 and DAD 10, demonstrated even higher H-Y antigen levels comparable to that of normal male peripheral blood lymphocytes. | Beta-Globulins |
Species of kalanchoe are rich in bioactive compounds and are widely used in folk medicine; however, these plants are not well known from the point of view of aroma. Two species, Kalanchoe pinnata and Kalanchoe daigremontiana, were examined after six months and two years of growth and their vitamin C content, succulence, and aroma composition were determined. The efficiency of juice extraction was highest (72%) for the leaves of K. daigremontiana after six months of growth. The concentration of vitamin C was highest in juices from two-year-old plants and much higher in the juice of K. pinnata (81 mg/100 g). SPME/GC/MS analysis identified 32 aroma components, considering those with the spectrum similarity over 75%. The main components were furan-2-ethyl, hexanal, 2-hexenal, 2,4-hexadienal, 1-octen-3-ol, nonanal. The quantitative relations of these compounds were somewhat different in the two species. The most dominant component, 2-hexenal, is responsible for the green-like aroma noted by the sensory panel. | Kalanchoe |
Central auditory disorders in children and adults have become more widely recognized in patients seen by otolaryngologists and audiologists. This article briefly defines those clinical entities, discusses the historic background of testing, and describes current and future test approaches to assessment of central auditory disorders. | Audiometry, Evoked Response |
A glucagon knock-out mouse with preserved GLP-1 and GLP-2 secretion allows for the improved study of transplanted human islets and glucagon responses- providing an unprecedented resource in human alpha-cell and diabetes research. | Glucagon-Secreting Cells |
This review traces the structural maturation of the human auditory system, and compares the timeline of anatomical development with cotemporaneous physiological and behavioral events. During the embryonic period, there is formation of basic structure at all levels of the system, i.e. the inner ear, the brainstem pathway, and the cortex. The second trimester is a time of rapid growth and development, and by the end of this period, the cochlea has acquired a very adult-like configuration. During the perinatal period, the brainstem reaches a mature state, and brainstem activity is reflected in behavioral responses to sound, including phonetic discrimination, and in evoked brainstem and early middle latency responses. The perinatal period is also the time of peak development of brainstem input to the cortex through the marginal layer, and of the long latency cortical potentials, the N(2) and mismatch negativity. In early childhood, from the sixth post-natal month to age five, there is progressive maturation of the thalamic projections to the cortex and of the longer latency Pa and P(1) evoked potentials. Later childhood, from six to twelve years, is the time of maturation of the superficial cortical layers and their intracortical connections, accompanied by appearance of the N(1) potential and improved linguistic discriminative abilities. Some consideration is given to the potential negative effects of deafness-induced sound deprivation during the perinatal period and childhood. | Cochlear Nerve |
MicroRNA-135a-5p has been reported to play a potential role in the generation of new neurons. However, the underlying targets of miR-135a-5p in regulating neuronal differentiation have been poorly understood. Our study recently has uncovered that Sox6 and CD44 genes were significantly downregulated during neuronal differentiation of P19â¯cells, a multipotent cell type. We then found that Sox6 directly bound to the promoter of CD44. Importantly, we identified Sox6 as a direct target of miR-135a-5p. Additionally, we demonstrated that miR-135a-5p is crucial for the neuronal differentiation of P19â¯cells. More significantly, we found that Sox6 overexpression could overturn miR-135a-5p-mediated neuronal differentiation and dendrite development. In conclusion, these findings indicated that miR-135a-5p/Sox6/CD44 axis provides an important molecular target mechanism for neurodifferentiation." | Embryonal Carcinoma Stem Cells |
An unusual case of infantile myofibromatosis of the solitary type occurring in an intracranial location in a 48-day-old female infant is presented. To our knowledge, there are no other descriptions in the literature of infantile myofibromatosis with exclusively intracranial involvement. The immunohistochemical and electron microscopic findings confirm the myofibroblastic origin of the proliferation. | Myofibromatosis |
Bone tumors are relatively rare in the foot and ankle region. Many of them present as cystic lesions on plain films. Due to the relative rarity of these lesions and the complex anatomy of the foot and ankle region, identification of such lesions is often delayed or they get misdiagnosed and mismanaged. This review discusses the most common cystic tumors of the foot and ankle including their radiographic features and principles of management." | Neoplasms, Connective and Soft Tissue |
A seven-year-old girl with fascioliasis was treated with rafanoxide which is used for therapy of fascioliasis in sheep and cattle. This is the first report in the literature concerning the usage of rafanoxide in children according to our knowledge. Rafanoxide was given in a single dose of 7.5 mg per kg body weight orally. | Salicylamides |
The physical examination is an essential clinical skill. The traditional approach to teaching the physical exam has involved a comprehensive head-to-toe" checklist, which is often used to assess students before they begin their clinical clerkships. This method has been criticized for its lack of clinical context and for promoting rote memorization without critical thinking. In response to these concerns, Gowda and colleagues surveyed a national sample of clinical skills educators in order to develop a consensus "core" physical exam, which they report in this issue. The core physical exam is intended to be performed for every patient admitted by students during their medicine clerkships and to be supplemented by symptom-driven "clusters" of additional history and physical exam maneuvers.In this commentary, the authors review the strengths and limitations of this Core + Clusters technique as well as the head-to-toe approach. They propose that the head-to-toe still has a place in medical education, particularly for beginning students with little knowledge of pathophysiology and for patients with vague or multiple symptoms. The authors suggest that the ideal curriculum would include teaching both the head-to-toe and the Core + Clusters exams in sequence. This iterative approach to physical exam teaching would allow a student to assess a patient in a comprehensive manner while incorporating more clinical reasoning as further medical knowledge is acquired." | Physical Examination |
Male sterility has been used for crop hybrid breeding for a long time. It has contributed greatly to crop yield increase. However, the genetic basis of male sterility has not been fully elucidated. Here, we report map-based cloning of the cabbage (Brassica oleracea) dominant male-sterile gene Ms-cd1 and reveal that it encodes a PHD-finger motif transcription factor. A natural allele Ms-cd1(PDelta-597,) resulting from a 1-bp deletion in the promoter, confers dominant genic male sterility (DGMS), whereas loss-of-function ms-cd1 mutant shows recessive male sterility. We also show that the ethylene response factor BoERF1L represses the expression of Ms-cd1 by directly binding to its promoter; however, the 1-bp deletion in Ms-cd1(PDelta-597) affects the binding. Furthermore, ectopic expression of Ms-cd1(PDelta-597) confers DGMS in both dicotyledonous and monocotyledonous plant species. We thus propose that the DGMS system could be useful for breeding hybrids of multiple crop species. | Plant Infertility |
Li et al present the results of a proximity-interaction screen in mammalian cells for the effector proteins of 25 members of the Arf family of small GTPases. This study has generated an important resource for those working in several areas of cell biology and provided an initial characterisation of two new cellular roles for some of the least well studied members of this family, the regulation of PLD1 by ARL11/14 in phagocytosis, and the regulation of PI4KB by ARL5A/5B in the Golgi. | ADP-Ribosylation Factors |
As the largest and among the most behaviourally complex extant terrestrial mammals, proboscideans (elephants and their extinct relatives) are iconic representatives of the modern megafauna. The timing of the evolution of large brain size and above average encephalization quotient remains poorly understood due to the paucity of described endocranial casts. Here we created the most complete dataset on proboscidean endocranial capacity and analysed it using phylogenetic comparative methods and ancestral character states reconstruction using maximum likelihood. Our analyses support that, in general, brain size and body mass co-evolved in proboscideans across the Cenozoic; however, this pattern appears disrupted by two instances of specific increases in relative brain size in the late Oligocene and early Miocene. These increases in encephalization quotients seem to correspond to intervals of important climatic, environmental and faunal changes in Africa that may have positively selected for larger brain size or body mass. | Proboscidea Mammal |
PURPOSE: To report visual and intraocular pressure (IOP) outcomes of 4 eyes in 2 patients with Weill Marchesani Syndrome having ocular fearures of spherophakia and secondary glaucoma who underwent fibrin glue assisted intrascleral fixation of intraocular lens (IOL). METHODS: Detailed anterior and posterior segment evaluation assessing best corrected visual acuity (BCVA), IOP, central corneal thickness was done in all. Lensectomy, vitrectomy with glued Intrascleral fixation of 3 piece intraocular lens was done. Post operative BCVA and IOP were assessed. RESULTS: Visual acuity and IOP control improved post-operatively. CONCLUSIONS: Glued IOL implantation is an effective method to visually rehabilitate and control glaucoma in patients with Weill Marchesani Syndrome. | Weill-Marchesani Syndrome |
Purine nucleoside phosphorylase deficient severe combined immunodeficiency (PNP SCID) is one of the rare autosomal recessive primary immunodeficiency disease, and the data on epidemiology and outcome are limited. We report the successful management of a child with PNP SCID and present a systematic literature review of published case reports, case series, and cohort studies on PNP SCID listed in PubMed, Web of Science, and Scopus from 1975 until March 2022. Forty-one articles were included from the 2432 articles retrieved and included 100 PNP SCID patients worldwide. Most patients presented with recurrent infections, hypogammaglobulinaemia, autoimmune manifestations, and neurological deficits. There were six reported cases of associated malignancies, mainly lymphomas. Twenty-two patients had undergone allogeneic hematopoietic stem cell transplantation with full donor chimerism seen mainly in those receiving matched sibling donors and/or conditioning chemotherapy before the transplant. This research provides a contemporary, comprehensive overview on clinical manifestations, epidemiology, genotype mutations, and transplant outcome of PNP SCID. These data highlight the importance of screening for PNP SCID in cases presented with recurrent infections, hypogammaglobulinaemia, and neurological deficits." | Severe Combined Immunodeficiency |
It is difficult at times to know if the welfare and well-being of an organization is being best served by the individuals who make decisions on its behalf. Sometimes decisions made are driven more by the needs of individual persons rather than by the needs of the organization. Company politics, conflicts, work relationships, territory and turf, individual status and power and personality issues all influence what happens and how decisions are made. Major decisions in areas such as downsizing, re-organization and corporate strategy are often made by individuals. Do these decisions best suit the agenda of the organization or reflect the agenda of the individual? Who looks after the organizational agenda? Noer's (1993) model is used to illustrate how what is best for the organization, and not just individuals within it, can be attained. | Organizational Objectives |
Cytokines play critical roles in regulating all aspects of immune responses, including lymphoid development, homeostasis, differentiation, tolerance and memory. Interleukin (IL)-12 is especially important because its expression during infection regulates innate responses and determines the type and duration of adaptive immune response. IL-12 induces interferon-gamma (IFN-gamma) production by NK, T cells, dendritic cells (DC), and macrophages. IL-12 also promotes the differentiation of naive CD4+ T cells into T helper 1 (Th1) cells that produce IFN-gamma and aid in cell-mediated immunity. As IL-12 is induced by microbial products and regulates the development of adaptive immune cells, IL-12 plays a central role in coordinating innate and adaptive immunity. IL-12 and the recently identified cytokines, IL-23 and IL-27, define a family of related cytokines that induce IFN-gamma production and promote T cell expansion and proliferation. | Receptors, Interleukin-12 |
The c-myc proto-oncogene is involved in various cellular processes including cell growth, proliferation, and apoptosis. Overexpression and deregulated expression of the gene have been previously linked to several lineage-unrelated, aggressive, and poorly differentiated tumors. The expression of c-myc has also been implicated in hematopoiesis and has been shown to play a crucial role in angiogenesis via a vascular endothelial growth factor-dependent mechanism. This gives c-myc a dual oncogenic function in that tumor growth requires both cell proliferation and angiogenesis to ensure survival and confer an effective malignancy. Amplification of c-myc has been recently reported to be a recurrent genetic alteration in angiosarcomas secondary to irradiation and/or chronic lymphedema. Of note, however, no c-myc gene abnormalities have been demonstrated in cases of primary angiosarcomas or postradiation atypical vascular lesions. More recently, our own experience indicates that c-myc amplification is not normally found in the Kaposi sarcoma and cannot be correlated with expression of the c-Myc protein. This comprehensive review outlines the structure, normal functions, and effects of the deregulated expression of c-myc with particular emphasis on its role in angiogenesis and select cutaneous vascular neoplasms. | Proto-Oncogene Proteins c-myc |
The adverse circumstances occasioned by disasters rarely remain static but rather continue to evolve, temporally and spatially, rendering preplanned response operations uncertain, at best, and ineffectual, at worst. As such, disaster management professionals need to think critically to implement response strategies best suited to the circumstances at hand, with the best available information. This paper provides an overview of critical thinking, and its importance in helping leaders provide order to the chaos often associated with disaster response and recovery efforts. Critical thinking skills include the ability to identify and define a problem, recognise assumptions, evaluate arguments, and apply inductive and deductive reasoning to draw conclusions from the available information. Understanding and improving a leader's critical thinking skills helps to provide a sense of confidence, trust and authority during a community-wide crisis. As such, emergency management professionals must continually enhance their critical thinking skills. | Thinking |
The measurement of hormones in urine has become a widely used technique in primatology. Because urine concentration varies according to fluid intake, concentration must be measured in each sample collected, and hormone values are always expressed per unit of concentration. Traditionally, creatinine has been used as a concentration index, but some studies in humans have shown that creatinine varies among populations and even within and between individuals within a population, and that it begins to degrade after just one freeze-thaw cycle. In addition, creatinine measurement is relatively time-consuming and expensive and creates hazardous waste. In this study, we tested the hypothesis that specific gravity, or the ratio of the density of a sample to that of water, is highly correlated with creatinine measurement in urine samples collected from captive chimpanzees at the New Iberia Research Center in Louisiana and wild chimpanzees at the Ngogo study site in the Kibale National Park, Uganda. We found that specific gravity and creatinine were highly correlated in both captive (N=124) and wild (N=13) chimpanzee samples, and that specific gravity measurement was robust to actual and simulated transport conditions and repeated freeze-thaw cycles. We recommend that researchers consider specific gravity measurement as a preferable alternative to creatinine measurement in their studies of primate endocrinology. | Urinalysis |
Somatic embryogenesis and organogenesis in Lilium pumilum were successfully regulated by picloram, alpha-naphthaleneacetic acid (NAA), and 6-benzyladenine (BA). In organogenesis, the highest shoot regeneration frequency (92.5%) was obtained directly from bulb scales on Murashige and Skoog (MS) medium containing 2.0 mg L(-1) BA and 0.2 mg L(-1) NAA, while organogenic callus (OC) formed from leaves on MS medium supplemented with 1.0 mg L(-1) BA and 0.5 mg L(-1) NAA. Following subculture, 76.7% of OC regenerated shoots. In somatic embryogenesis, the combination of picloram and NAA increased the amount of embryogenic callus (EC) that formed with a maximum on 90.7% of all explants which formed 11 somatic embryos (SEs) per explant. Differences between EC and OC in cellular morphology and cell differentiation fate were easily observed. SEs initially formed via an exogenous or an endogenous origin. The appearance of a protoderm in heart-shaped SE and the bipolar shoot-root development in oval-shaped SE indicated true somatic embryogenesis. This protocol provides a new and detailed regulation and histological examination of regeneration pattern in L. pumilum. | Picloram |
Ilex asprella is a widely used herbs in Traditional Chinese Medicine for treating viral infection and relieving inflammation. Due to the earlier fruiting period of I. asprella, it is the major food source for frugivores in summer. Despite its pharmacological and ecological importance, a reference genome for I. asprella is lacking. By using Illumina, stLFR and Omni-C sequencing data, we present the first chromosomal-level assembly for I. asprella. The genome assembly size is 804 Mbp, with Benchmarking Universal Single-Copy Orthologs (BUSCO) score 94.4% for eudicotyledon single copy genes. Transcriptomes of leaves, stems, flowers, premature fruits and roots were analyzed, providing 39,215 gene models. The complete set of genes involved in the triterpenoids production is disclosed for the first time. We have also found the oxidosqualene cyclases (OSCs), CYP716s and UDP-glycosyltransferases (UGTs), which are responsible for the modification of triterpenoid backbones, resulting in the high variety of triterpenoid saponins. | Ilex |
Programmed cell death (PCD) is an essential part of organismal development and plays fundamental roles in host defense against pathogens and the maintenance of homeostasis. However, excess activation of PCD pathways has proven to be detrimental and can drive disease. Additionally, resistance to PCD can also contribute to disease development. Modulation of PCD, therefore, has great therapeutic potential in a wide range of diseases, including infectious, neurodegenerative, autoinflammatory, and metabolic diseases and cancer. Nevertheless, manipulation of cell death and inflammation for therapeutic intervention is a delicate process, highly specific to the context of the disease of interest, making the selection of the appropriate target molecule crucially important. Several PCD pathways are associated with innate immunity, including pyroptosis, apoptosis, necroptosis, and PANoptosis, which is defined as an inflammatory PCD pathway with key features of pyroptosis, apoptosis, and/or necroptosis that cannot be accounted for by any of these three PCD pathways alone. All of these PCD pathways are regulated by upstream sensors and signaling cascades that assemble multimeric complexes to serve as activation platforms for downstream molecules; these sensors and signaling molecules provide attractive target points for therapeutic intervention. Here, we discuss the molecular mechanisms of innate immune-mediated cell death in health and disease, with a particular focus on the molecules putatively involved in the formation of the PANoptosome and the induction of inflammatory cell death. Further, we discuss the implications and feasibility of targeting these molecules to improve disease outcomes, as well as current clinical approaches. | Cell Physiological Phenomena |
Scholarly understanding of the nature of the science around silicosis has been strongly influenced, in recent years, by the idea that the mine doctors were responsible for hiding an epidemic, on the mines and in the countryside. In this paper, I try to show that the opposite was in fact the case, and that the science and government institutions for the regulation of silicosis and tuberculosis in white and black male workers were distinctively elaborated, and very largely successful in tracking and controlling the disease. This singular visibility, funded by the mines, stands in marked contrast with disease in general in South Africa, and forms a major part of the explanation for the very strong association of silicosis with mine work. | Silicotuberculosis |
BACKGROUND: Distraction-resisting forces that are generated during distraction osteogenesis can be responsible for complications, including a lag effect on fibular distraction leading to a tibiofibular distraction difference, tibial axial deviation, and distraction at the proximal and distal tibiofibular joints. We investigated the nature of distraction-resisting forces by studying their correlation with these parameters. METHODS: One hundred and eleven tibial lengthening procedures in sixty-three patients were chosen. Seventy-six segments underwent lengthening with an Ilizarov ring fixator, and thirty-five segments had lengthening over an intramedullary nail. Serial radiographs were evaluated with regard to the amounts of tibiofibular distraction difference, proximal tibiofibular joint distraction, distal tibiofibular joint distraction, tibial axial deviation, and heel malalignment. Clinically, laxity at the knee was evaluated and fibular head instability was assessed. Variations in all of these parameters were evaluated with respect to tibiofibular joint fixation, etiology, skeletal maturity, lengthening over an intramedullary nail, and amount of lengthening. RESULTS: The mean tibiofibular distraction difference was 19.1 +/- 10.6 mm (range, 2 to 51 mm), the mean proximal tibiofibular joint distraction was 10.1 +/- 6.8 mm (range, 0 to 33 mm), and the mean tibial valgus angulation was 8.7 degrees +/- 4.4 degrees . At the time of the latest follow-up, twenty-eight segments (25%) had lateral knee joint laxity at 30 degrees of knee flexion and eight segments (7%) had fibular head subluxation at 90 degrees of knee flexion. Twenty-four (86%) of the twenty-eight cases of knee laxity were observed in skeletally immature patients. The tibiofibular distraction difference, proximal tibiofibular joint distraction, and tibial valgus angulation were significantly greater in the group without fixation of the proximal tibiofibular joint. A significant decrease in the tibial valgus angulation and knee laxity was found in patients with lengthening over an intramedullary nail. In the intramedullary nail group, after fixation of the proximal tibiofibular joint, the tibiofibular distraction difference and the proximal tibiofibular joint distraction decreased; however, the proportion of cases with clinically important tibial valgus angulation (>10 degrees ) increased significantly. CONCLUSIONS: Fixing both tibiofibular joints with a single Ilizarov wire decreases proximal tibiofibular joint distraction; however, more secure fixation would help to decrease the prevalence of delayed knee laxity. When tibial lengthening is performed over an intramedullary nail, avoiding proximal tibiofibular joint fixation will limit tibial valgus angulation. Limiting lengthening to <25% will decrease the proportion of cases with knee laxity, and limiting lengthening to <50% will significantly limit tibial valgus angulation. | Ilizarov Technique |
253 percutaneous transhepatic cholangiographies with Chiba needle were performed. In 83% of the cases the biliary tract could be visualized. In the patients with extrahepatic cholestasis 92% success was achieved, while only 48% success in the cases with intra-hepatic cholestasis. Complications were developed in 3,87% of cases (choleperitoneum 4, cholangitis 2, hemorrhage 2, paralytic ileum 1, hemobilia 2). There was no mortality. Patients with dilated biliary tract should be operated upon in no more than 24 hours following the procedure. | Cholangiography |
The effect of the extracts of Epimedium brevicornum Maxim. was investigated on proliferative activity in vitro. The osteoblast-like UMR106 cells was employed as an osteoblast model. The EtOH extract and the n-butanol fraction from the crude extract were found to show proliferation stimulating activity. Three flavonoid compounds (icariin, epimedin B and epimedin C) were isolated from this fraction by activity-guided assay, and the effects on cell proliferation were studied. Icariin produced the most significant promoting effect on the proliferation in osteoblast-like UMR106 cells. The results suggested that E. brevicornum Maxim. extracts might have potential activity against osteoporosis, and flavonoids such as icariin might be the active constituents stimulating osteoblasts. | Epimedium |
In vitro culture conditions affecting the transformation efficiency from zygote to ookinete for Plasmodium gallinaceum were examined, as a step toward improving the overall efficiency of in vitro culture systems for sporogonic stages. Gametocytes from infected chickens were allowed to fertilize in vitro and the resulting zygotes were purified and cultured. The time course for ookinete development in vitro was similar to that seen in Aedes aegypti mosquitoes. Supplementing a basal M-199 culture medium with heat-inactivated chicken serum and glucose did not affect transformation efficiency, but resulted in a four-fold increase in infectivity to mosquitoes when fed back to Ae. aegypti. Transformation from zygote to ookinete increased 5- to 10-fold when zygotes were cocultured with one of six different mosquito cell lines or a Drosophila cell line. Under optimal conditions, transformation efficiencies of up to 75% were observed. The presence of insect cells also increased the longevity of ookinetes in culture up to 42 h, while in acellular cultures ookinetes degenerated after about 24 h. The stimulatory effect was apparently not due to a factor secreted into the medium by the cells. | Plasmodium gallinaceum |
Patient and public involvement (PPI) in health research is of increasing interest internationally, as well as being a means to enhance the quality and relevance of research. PPI was one of the main themes and parallel sessions at The Nordic Health Research and Innovation Networks in Oslo in 2017. In this short comment/debate article, we outline some of the experiences from the event. Importantly, there are many common challenges. More collaboration across the borders could ensure a broader range of experience in the field and provide better ways of developing and evaluating PPI in health research. | Community Participation |
Numerous studies have provided evidence regarding the involvement of protein S-nitrosylation in the progression of Alzheimer's disease (AD) pathology and its implication in the formation and accumulation of misfolded protein aggregates. The identification of S-nitrosylated proteins can be a major step toward the understanding of mechanisms leading to neuronal degeneration. The present study targeted S-nitrosylated proteins in AD hippocampus, substantia nigra and cortex using the following work-flow that combines S-nitrosothiol-specific antibody detection, classical biotin switch method labeled with fluorescence dye followed by electrospray ionization quadrupole time of flight tandem MS (ESI-QTOF MS/MS) identification. Endogenous nitrosocysteines were identified in 45 proteins, mainly involved in metabolism, signaling pathways, apoptosis and redox regulation as assigned by REACTOME and KEGG pathway database analysis. Superoxide dismutase (SOD2) [Mn], fructose-bisphosphate aldolase C (ALDOC) and voltage-dependent anion-selective channel protein 2 (VDAC2) showed differential S-nitrosylation signal, not previously reported in AD regions. Extensive neuronal atrophy with increased protein S-nitrosylation in AD regions is also evident from immunofluorescence studies using S-nitrosocysteine antibody. A number of plausible cysteine modification sites were predicted via Group-based Prediction System-S-nitrosothiols (GPS-SNO) 1.0 while STRING 8.3 analysis revealed functional annotations in the modified proteins. The findings are helpful in characterization of functional abnormalities and may facilitate the understanding of molecular mechanisms and biological function of S-nitrosylation in AD pathology." | Voltage-Dependent Anion Channel 2 |
Medication errors due to look-alike drugs put patients at risk and can be fatal. Neuromuscular blocking agents, such as vecuronium, can cause awake-paralysis in patients if administered as a single agent. Recent literature reported six cases in which vecuronium was inadvertently administered instead of the antibiotic drug cefazolin. This article describes a standardized quality improvement process used at The Johns Hopkins Hospital that was locally implemented following an adverse drug event and culminated in a nationwide FDA-mandated drug recall of vecuronium. | Drug Recalls |
The characteristics of the interaction of Na-K pumps of high potassium (HK) and low potassium (LK) goat red blood cells with ouabain have been determined. The rate of inhibition by ouabain of the pump of HK cells is greater than the rate of inhibition of the pumps of LK cells. Treatment of LK cells with an antibody (anti-L) raised in HK sheep by injecting LK sheep red cells increases the rate of inhibition of the LK pumps by ouabain to that characteristic of HK pumps; reduction of intracellular K (K(c)) in LK cells increases the rate at which ouabain inhibits their pumps and exposure of these low K(c) cells to anti-L does not affect the rate of inhibition. There is considerable heterogeneity in the pumps of both HK and LK cells in the rate at which they interact with ouabain or the rate at which they pump or both. LK pumps which are sensitive to stimulation by anti-L bind ouabain less rapidly than the remainder of the LK pumps and exposure to antibody increases the rate at which ouabain binds to the sensitive pumps; the difference between the two types of pumps disappears if intracellular K is very low. The calculated number of ouabain molecules bound at 100% inhibition of the pump is about the same for HK and LK cells. Although exposure to anti-L increases the apparent number of ouabain binding sites in LK cells at normal K(c), it does not alter the apparent number of sites in LK cells when K(c) has been reduced. | Ouabain |
With accumulating evidence and improved outcomes along with recognition that modern biological therapies are not universally effective, require chronic administration and have high acquisition costs, hematopoietic stem cell transplantation (HSCT) has become an emerging direction for cell therapy in autoimmune diseases (ADs). The goal of this therapy is to induce medication-free remissions by resetting the immune system into a naive and self-tolerant state through eradication of the autoreactive immunologic memory and profound re-configuration of the immune system induced by the transplant procedure. Safety of HSCT has generally improved by implementing internal quality management and external accreditation. Inter-disciplinary guidelines for patient selection, transplant technique and supportive care along with greater center experience should optimize safe and appropriate delivery of HSCT in specific ADs. In this review, we discuss the current role and future perspectives of HSCT in AD, focusing on recent published clinical and scientific studies and recommendations in the field." | Clonal Selection, Antigen-Mediated |
The p53 protein, a negative regulator of cell growth, plays an important role in the pathogenesis of many human tumours following gene mutation and/or deletion. We screened a large number of sporadic pituitary tumours for p53 protein accumulation suggestive of gene mutation. Samples were divided into benign adenomas (n = 95) and invasive tumours with local or distant invasion (n = 26). All main tumour classes were represented. Putative p53 mutations were detected by immunohistochemistry on paraffin-embedded sections using polyclonal CM-1 and monoclonal DO-7 and PAb1801 antibodies. Results were compared to normal post-mortem pituitary tissue controls (n = 17). p53 protein accumulation was detected in invasive tumours (16%), but only in corticotrophinomas (2/4) and non-functional tumours (4/15). In non-invasive adenomas, protein accumulation was observed only in ACTH-secreting tumours where 50% were positive (16/32). No protein accumulation was identified in any control tissue. These results indicate that p53 protein accumulation may play a role in the development of Cushings adenomas and in the progression of non-functional tumours to the invasive state. | Adenoma, Basophil |
The identification of the molecular mechanisms controlling early cell fate decisions in mammals is of paramount importance as the ability to determine specific lineage differentiation represents a significant opportunity for new therapies. Pancreatic Progenitor Cells (PPCs) constitute a regenerative reserve essential for the maintenance and regeneration of the pancreas. Besides, PPCs represent an excellent model for understanding pathological pancreatic cellular remodeling. Given the lack of valid markers of early endoderm, the identification of new ones is of fundamental importance. Both products of the Ink4a/Arf locus, in addition to being critical cell-cycle regulators, appear to be involved in several disease pathologies. Moreover, the locus' expression is epigenetically regulated in ES reprogramming processes, thus constituting the ideal candidates to modulate PPCs homeostasis. In this study, starting from mouse embryonic stem cells (mESCs), we analyzed the early stages of pancreatic commitment. By inducing mESCs commitment to the pancreatic lineage, we observed that both products of the Cdkn2a locus, Ink4a and Arf, mark a naive pancreatic cellular state that resembled PPC-like specification. Treatment with epi-drugs suggests a role for chromatin remodeling in the CDKN2a (Cycline Dependent Kinase Inhibitor 2A) locus regulation in line with previous observations in other cellular systems. Our data considerably improve the comprehension of pancreatic cellular ontogeny, which could be critical for implementing pluripotent stem cells programming and reprogramming toward pancreatic lineage commitment." | Hepatocyte Nuclear Factor 3-beta |
Painting mice on the skin with the diazonium salt of p-arsanilic acid elicited two types of T cell activity. One was restricted by the I region of the major histocompatibility complex and was responsible for the transfer of azobenzenearsonate (ABA) sensitivity to naive mice. The other was H-2K restricted and could be demonstrated by its ability to interact specifically with ABA-coupled cells in vitro and to inhibit nonspecifically the transfer of sensitivity by cells sensitized either to ABA or to another antigen. Free antigen, or antibody directed against the cross-reactive idiotype on the anti-ABA antibodies of A/J mice, could inhibit the H-2K-restricted suppressive activity induced in the ABA immune A/J cells. | p-Azobenzenearsonate |
Double-strand break repair is required for neural development, and brain cells contain somatic genomic variations. Now, Wei et al. demonstrate that neural stem and progenitor cells undergo very frequent DNA breaks in a very restricted set of genes involved in neural cell adhesion and synapse function. | DNA Breaks |
The binding of neomycin sulfate (NS)/paromomycin sulfate (PS) with DNA was investigated by fluorescence quenching using acridine orange (AO) as a fluorescence probe. Fluorescence lifetime, FT-IR, circular dichroism (CD), relative viscosity, ionic strength, DNA melting temperature, and molecular docking were performed to explore the binding mechanism. The binding constant of NS/PS and DNA was 6.70 x 10(3)/1.44 x 10(3) L mol(-1) at 291 K. The values of DeltaH(theta), DeltaS(theta), and DeltaG(theta) suggested that van der Waals force or hydrogen bond might be the main binding force between NS/PS and DNA. The results of Stern-Volmer plots and fluorescence lifetime measurements all revealed that NS/PS quenching the fluorescence of DNA-AO was static in nature. FT-IR indicated that the interaction between DNA and NS/PS did occur. The relative viscosity and melting temperature of DNA were almost unchanged when NS/PS was introduced to the solution. The fluorescence intensity of NS/PS-DNA-AO was decreased with the increase in the ionic strength. For CD spectra of DNA, the intensity of positive band at nearly 275 nm was decreased and that of negative band at nearly 245 nm was increased with the increase in the concentration of NS/PS. The binding constant of NS/PS with double-stranded DNA (dsDNA) was larger than that of NS/PS with single-stranded DNA (ssDNA). From these studies, the binding mode of NS/PS with DNA was evaluated to be groove binding. The results of molecular docking further indicated that NS/PS could enter into the minor groove in the A-T rich region of DNA. | Acridine Orange |
Although nearly half of the synaptic input to neurons in the dorsal thalamus comes from the cerebral cortex, the role of corticothalamic projections in sensory processing remains elusive. Although sensory afferents certainly establish the basic receptive field properties of thalamic neurons, increasing evidence indicates that feedback from the cortex plays a crucial role in shaping thalamic responses. Here, we review recent work on the corticothalamic pathways associated with the visual, auditory, and somatosensory systems. Collectively, these studies demonstrate that sensory responses of thalamic neurons result from dynamic interactions between feedforward and feedback pathways. | Feedback, Physiological |
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