Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of glycosylation on heparin binding and antithrombin activation by heparin

Antithrombin (AT), a serine protease inhibitor, circulates in blood in two major isoforms, α and β, which differ in their amount of glycosylation and affinity for heparin. After binding to this glycosaminoglycan, the native AT conformation, relatively inactive as a protease inhibitor, is converted to an activated form. In this process, β‐AT presents the higher affinity for heparin, being suggested as the major AT glycoform inhibitor in vivo. However, either the molecular basis demonstrating the differences in heparin binding to both AT isoforms or the mechanism of its conformational activation are not fully understood. Thus, the present work evaluated the effects of glycosylation and heparin binding on AT structure, function, and dynamics. Based on the obtained data, besides the native and activated forms of AT, an intermediate state, previously proposed to exist between such conformations, was also spontaneously observed in solution. Additionally, Asn135‐linked oligosaccharide caused a bending in AT‐bounded heparin, moving such polysaccharide away from helix D, which supports its reduced affinity for α‐AT. The obtained data supported the proposal of an atomic‐level, solvent and amino acid residues accounting, putative model for the transmission of the conformational signal from heparin binding exosite to β‐sheet A and the reactive center loop, also supporting the identification of differences in such transmission between the serpin glycoforms involving helix D, where the Asn135‐linked oligosaccharide stands. Such intramolecular rearrangements, together with heparin dynamics over AT surface, may support an atomic‐level explanation for the Asn135‐linked glycan influence over heparin binding and AT activation. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Cutaneous Mucinosis in a Strain of Brown–Egg Laying Chickens

Cutaneous mucinosis is a cutaneous disorder described in humans, dogs, and rarely cats but never reported in birds. Twenty-six brown egg–laying chickens between ages 43 and 46 weeks had a history of feather loss, scaly, dry skin, weight loss, and decreased egg production. Microscopic findings in the skin included fragmentation of collagen bundles and interstitial, periadnexal, and perivascular dermal accumulation of wispy, mildly basophilic material that was also occasionally observed within the follicular epithelium. A moderate lymphoplasmacytic and heterophilic perivascular dermatitis was also observed. The wispy to granular material was diffusely Alcian blue positive and periodic acid–Schiff negative (consistent with mucin), suggesting a diagnosis of primary or secondary cutaneous mucinosis. The cause of this condition could not be determined.
Mucosal biofilm formation on middle-ear mucosa in the chinchilla model of otitis media.

CONTEXT Chronic otitis media with effusion (OME) has long been considered to be a sterile inflammatory process. The previous application of molecular diagnostic technologies to OME suggests that viable bacteria are present in complex communities known as mucosal biofilms; however, direct imaging evidence of mucosal biofilms associated with OM is lacking. OBJECTIVE To determine whether biofilm formation occurs in middle-ear mucosa in an experimental model of otitis media. DESIGN AND MATERIALS A total of 48 research-grade, young adult chinchillas weighing 500 g were used for 2 series of animal experiments: one to obtain specimens for scanning electron microscopy and the other to obtain specimens for confocal laser scanning microscopy using vital dyes. In each series, 21 animals were bilaterally injected with viable Haemophilus influenzae bacteria and 1 was inoculated to account for expected mortality. Three served as negative controls. Effusions and mucosal specimens were collected from 2 infected animals that were euthanized at 3, 6, 12, and 24 hours and at days 2, 4, 5, 10, 16, and 22 after inoculation. MAIN OUTCOME MEASURES Images were analyzed for biofilm morphology, including presence of microcolony formation and for presence of bacteria on tissue surfaces. RESULTS Scanning electron microscopy demonstrated that biofilm formation was evident in all specimens from animals beginning 1 day after infection and was present through 21 days. Confocal laser scanning microscopy indicated that bacteria within the biofilms are viable. CONCLUSION These preliminary findings provide evidence that mucosal biofilms form in an experimental model of otitis media and suggest that biofilm formation may be an important factor in the pathogenesis of chronic otitis media with effusion.
Collagen‐rich variant of benign epithelioid peripheral nerve sheath tumor of the skin

Schwannoma and neurofibroma account for the majority of cutaneous benign peripheral nerve sheath tumors and usually pose little diagnostic difficulty in their classic forms. In rare instances, however, benign peripheral nerve sheath tumors may display epithelioid morphology and lack otherwise usual features of schwannoma or neurofibroma, making classification difficult. These unusual changes may prompt consideration of other benign neoplasms or a malignancy. Benign epithelioid peripheral nerve sheath tumor (BEPNST) is a somewhat non‐specific term recently proposed to describe these neoplasms of imprecise histogenesis. Also diagnostically challenging, rare BEPNST with unusual arrangements of extracellular collagen have been described and reported as neuroblastoma‐like schwannoma and collagenous spherulosis. We report a unique case of cutaneous BEPNST with a peculiar arrangement of abundant extracellular collagen, different than the previously observed patterns. Specifically, the neoplastic cells in this tumor were nearly obscured by the collagen, which formed large nodules and compressed the majority of the few remaining tumor cells to the periphery of the lesion. This excessive collagen production emphasizes the importance of adequate sampling to ensure a correct diagnosis.
Correlation between Audiovestibular Function Tests and Hearing Outcomes in Severe to Profound Sudden Sensorineural Hearing Loss

Objective: This study investigated whether audiovestibular function tests, namely auditory brain stem response (ABR) and vestibular-evoked myogenic potential (VEMP) tests were correlated to hearing outcomes after controlling the effects of other potential confounding factors in severe to profound sudden sensorineural hearing loss (SSHL). Design: Eighty-eight patients with severe to profound SSHL were enrolled in this study. Pretreatment hearing levels, results of audiovestibular function tests, and final hearing outcomes were recorded from retrospective chart reviews. Other factors, including age, gender, delay of treatment, vertigo, diabetes mellitus, and hypertension, were collected as well. Comparative analysis between multiple variables and hearing outcomes was conducted using the cumulative logits model in overall subjects. Further, multivariate analysis of prognostic factors was conducted in the stratified groups of severe (70 dB HL 90 dB HL) SSHL. Results: Multivariate analysis showed that pretreatment hearing levels, presence of vertigo, and results of ABR and VEMP testing were significant outcome predictors in the overall subjects. Stratification analysis demonstrated that both the presence of ABR and VEMP waveforms were significantly correlated with better hearing outcomes in the group of severe SSHL [ABR: adjusted odds ratio (aOR) = 14.7, 95% confidence interval (CI) = 1.78 to 122, p = 0.01; VEMP: aOR = 5.91, 95% CI = 1.18 to 29.5, p = 0.03], whereas the presence of vertigo was the only significant negative prognostic factor in the group of profound SSHL (aOR = 0.24, 95% CI = 0.06 to 0.95, p = 0.04). Other variables, including age, gender, diabetes mellitus, hypertension, and delay of treatment, were not significantly related to hearing outcomes in both groups (p > 0.05). A predictive hearing recovery table with the combined ABR and VEMP results was proposed for the group of severe SSHL. Conclusions: ABR and VEMP tests should be included in the battery of neurootological examinations in patients with severe SSHL because the presence of both waveforms might indicate favorable hearing outcomes. The presence of vertigo might portend a worse prognosis in patients with profound SSHL. A presumed table in predicting hearing outcomes was suggested for patients with severe SSHL.
Bis(7)-tacrine protects retinal ganglion cells against excitotoxicity via NMDA receptor inhibition.

AIM To investigate whether bis(7)-tacrine, a multifunctional drug, inhibits N-methyl-D-aspartate (NMDA) -activated current in retinal ganglion cells(RGC) and provides neuroprotection against retinal cell damage. METHODS Purified RGC cultures were obtained from retinas of 1-3 days old Sprague-Dawley(SD) rats, following a two-step immunopanning procedure. After 7 days of cultivation, the inhibition of NMDA-activated current by bis(7)-tacrine was measured by using patch-clamp recording techniques. In animal experiments, RGCs were damaged after intravitreal injection of NMDA (5µL, 40nmol) in adult rats. Bis(7)-tacrine(0.05, 0.1, 0.2mg/kg) or memantine(20mg/kg) was intraperitoneal administered to the rats fifteen minutes before intravitreally injection of NMDA. RGC damage was analyzed by histologic techniques, TUNEL and retrograde labeling techniques. RESULTS Whole-cell patch-clamp recordings demonstrated that NMDA (30µmol/L) resulted in approximately -50 pA inward currents that were blocked by bis(7)-tacrine(1µmol/L). Histological examination and retrograde labeling analysis revealed that bis(7)-tacrine induced a significant neuroprotective effect against NMDA-induced cell damage 7 days after NMDA injection. TUNEL staining showed that pretreatment with bis(7)-tacrine was effective in ameliorating NMDA-induced apoptotic cell loss in the retinal ganglion cell layer 18 hours after injection. CONCLUSION Bis(7)-tacrine possesses remarkable neuroprotective activities against retinal excitotoxicity through inhibition of NMDA receptors.
Primary site of action of ketoconazole on Candida albicans

Ketoconazole, an antifungal drug, completely inhibited the growth of Candida albicans 7N at concentrations of greater than or equal to 50 microgram/ml (94 microM). However, ketoconazole incompletely inhibited the growth of this opportunistic yeast at concentrations of 25 to 0.2 microgram/ml (47 to 0.4 microM). At these lower concentrations, 2,3,5-triphenyl tetrazolium chloride, an electron acceptor, was reduced by several strains of C. albicans. This effect resulted in red coloration of colonies. Concomitantly, this phenomenon was not antagonized in the presence of ergosterol. Furthermore, neither ketoconazole nor antimycin A inhibited the growth of C. albicans under anaerobic conditions, as revealed by a paper disk method. Ketoconazole at the concentrations stated above inhibited endogenous and exogenous respiration immediately after it was added to a system containing log phase C. albicans cells, as determined polarographically. At the same time, ketoconazole inhibited the activity of NADH oxidase at the mitochondrial level. In contrast, higher concentrations of ketoconazole (greater than 100 microM) were required to inhibit the activity of succinate oxidase from rat liver mitochondria. In addition, concentrations of ketoconazole greater than 100 microM were required to impair the uptake of labeled leucine and adenine and, subsequently, the incorporation of the former into protein and the latter into DNA and RNA in intact cells. On the other hand, ketoconazole at concentrations of 10, 1.0, and 0.4 microM had no effect on either membrane permeability or macromolecular synthesis.
Postmenopausal Estrogens and Risk of Myocardial Infarction in Diabetic Women

OBJECTIVE The effect of hormone replacement therapy on the risk of myocardial infarction in diabetic women has not been well studied. We conducted a case-control study of postmenopausal estrogen use and risk of incident myocardial infarction (MI) in pharmacologically treated diabetic women enrolled at Group Health Cooperative of Puget Sound, a large health maintenance organization in the state of Washington. RESEARCH DESIGN AND METHODS Case subjects (n = 212) were all postmenopausal women with treated diabetes who sustained an incident fatal or nonfatal MI between July 1986 and December 1994. Control subjects (n = 122) were treated diabetic women drawn from a stratified random sample of postmenopausal women without prior MI. Computerized pharmacy data and medical records were used to measure use of estrogens. Cardiovascular risk factors recorded from medical records, computerized pharmacy and laboratory data, and telephone interviews were used as adjustment variables. RESULTS In this study, 8.5% of case and 13.9% of control subjects were current users of estrogens. The relative risk (RR) of MI for current estrogen users was 0.51 (95% CI 0.22–1.15) relative to never users, adjusted for age, study year, weight, angina, and duration of treated diabetes. Among current estrogen users, risk of MI tended to decline with each additional year of estrogen use (adjusted RR – 0.78, 95% CI 0.56–1.08). Of those studied, 45.3% of case and 37.7% of control subjects were past users of estrogens (adjusted RR = 1.22,95% CI 0.71–2.09). CONCLUSIONS This study suggests that use of postmenopausal estrogens does not increase risk of MI in diabetic women and that sustained use may be of benefit.
Meta‐Analysis of P‐Wave Dispersion Values in Healthy Individuals: The Influence of Clinical Characteristics

Background: P‐wave dispersion (Pd) is an appealing marker for predicting the risk of developing atrial fibrillation. At present, no definitive cutoff value has been determined as to the diagnosis of high‐risk patients. Our aims were to evaluate P‐wave parameters of healthy subjects published in the literature, determine normal range and weighted means of Pd and P‐wave parameters, and investigate the influences of gender, age, and BMI on the weighted results.
Microbial Conversion of Tomato by a Plant Pathogenic Bacterium Pectobacterium atrosepticum: A Plant-Microbial Approach to Control Pathogenic Candida Species

This study was carried out to produce bioconverted products by microbial fermentation of tomato using a plant pathogenic bacterium Pectobacterium atrosepticum and to evaluate their in vitro antimycotic effect against pathogenic Candida species. The bioconverted products (500 μg/disc) provoked promising antimycotic effects against pathogenic isolates of Candida species as shown by the diameters of zones of inhibition (9 ± 0.6 to 14 ± 0.4 mm), along with their respective minimum inhibitory and minimum fungicidal concentration values, which increased from 250 to 1000 and 250 to 2000 μg/mL, respectively. With the viable counts of the tested fungal pathogens, exposure of the bioconverted products revealed a remarkable antimycotic effect. In addition, the morphology of a clinical isolate of C. glabrata KBN06P00368, visualized by scanning electron microscopy, showed a severe detrimental effect produced by the bioconverted products at the minimum inhibitory concentration (250 μg/mL). The bioconverted products significantly inhibited the in vitro growth of all the tested clinical and pathogenic laboratory isolates of Candida species. This study confirmed the potent antimycotic efficacy of the bioconverted products of tomato, hence justifying the therapeutic uses of bioconverted products in pharmaceutical preparations as an alternative approach to support the antifungal activity of conventional antimycotics.
Cytogenetic analysis of the chromosomal region immediately adjacent to the rosy locus in Drosophila melanogaster.

This report describes the genetic analysis of a region of the third chromosome of Drosophila melanogaster extending from 87D2-4 to 87E12-F1, an interval of 23 or 24 polytene chromosome bands. This region includes the rosy (ry, 3-52.0) locus, carrying the structural information for xanthine dehydrogenase (XDH). We have, in recent years, focused attention on the genetic regulation of the rosy locus and, therefore, wished to ascertain in detail the immediate genetic environment of this locus. Specifically, we question if rosy is a solitary genetic unit or part of a large complex genetic unit encompassing adjacent genes. Our data also provide opportunity to examine further the relationship between euchromatic gene distribution and polytene chromosome structure. ----The results of our genetic dissection of the rosy micro-region substantiate the conclusion drawn earlier (SCHALET, KERNAGHAN and CHOVNICK 1964) that the rosy locus is the only gene in this region concerned with XDH activity and that all adjacent genetic units are functionally, as well as spatially, distinct from the rosy gene. Within the rosy micro-region, we observed a close correspondence between the number of complementation groups (21) and the number of polytene chromosome bands (23 or 24). Consideration of this latter observation in conjunction with those of similar studies of other chhromosomal regions supports the hypothesis that each polytene chromosome band corresponds to a single genetic unit.
Risk Assessment of Listeria monocytogenes: Impact of Individual Cell Variability on the Exposure Assessment Step

Recently, the lag phase research in predictive microbiology is focusing more on the individual cell variability, especially for pathogenic microorganisms that typically occur in very low contamination levels, like Listeria monocytogenes. In this study, the effect of this individual cell lag phase variability was introduced in an exposure assessment study for L. monocytogenes in a liver pâté. A basic framework was designed to estimate the contamination level of pâté at the time of consumption, taking into account the frequency of contamination and the initial contamination levels of pâté at retail. Growth was calculated on pâté units of 150 g, comparing an individual‐based approach with a classical population‐based approach. The two different protocols were compared using simulations. If only the individual cell lag variability was taken into account, important differences were observed in cell density at the time of consumption between the individual‐based approach and the classical approach, especially at low inoculum levels, resulting in high variability when using the individual‐based approach. Although, when all variable factors were taken into account, no significant differences were observed between the different approaches, allowing the conclusion that the individual cell lag phase variability was overruled by the global variability of the exposure assessment framework. Even in more extreme conditions like a low inoculum level or a low water activity, no differences were created in cell density at the time of consumption between the individual‐based approach and the classical approach. This means that the individual cell lag phase variability of L. monocytogenes has important consequences when studying specific growth cases, especially when the applied inoculum levels are low, but when performing more general exposure assessment studies, the variability between the individual cell lag phases is too limited to have a major impact on the total exposure assessment.
Demographic characteristics of MS patients in Poland's upper Silesia region

Objectives: In Poland, no national registry of MS patients has yet been introduced. So far, no demographic studies have been conducted in patients with MS in Upper Silesia. The aim of the present study was to evaluate, for the first time, a selected demographic and clinical parameters in MS patients from the Upper Silesia region and compare these characteristics with previously published data from other regions of Poland. Materials & Methods: 640 patients with clinically defined MS, were prospectively and randomly selected for the study. Social, socio-economic, and demographic data were obtained through a questionnaire study. All subjects performed a self-assessment of their health condition using EQ-5D and EQ-VAS version questionnaires. Results: The ratio of women to men was 2.18. The average age of onset was 29.6 ± 11.1 years; the disease duration was 7.9 ± 4.5 years. The relapsing-remitting form of MS was diagnosed in 73.12%. In 71.25% the onset was monofocal and in 28.75% multifocal disease onset was observed. Among the studied population 339 (52.97%) patients were still employed. A mean EQ-VAS score of 66.11 ± 20.12 was calculated. Conclusions: Results from our study identify for the first time the demographic and clinical characteristics of the Upper Silesia MS population.
Fossil Echinoderms As Monitor of the Mg/Ca Ratio of Phanerozoic Oceans

Opinion has long been divided as to whether the Mg/Ca ratio of seawater remained constant during the Phanerozoic or underwent substantial secular change. Existing empirical evidence for the Mg/Ca of ancient seawater provides a poorly resolved and often controversial signal. Echinoderm fossils that have retained their bulk original chemistry, despite micrometer-scale changes, preserve a record of seawater Mg/Ca and confirm that major changes in Mg/Ca occurred during the Phanerozoic. Echinoderms from the Cambrian and from the Carboniferous to the Triassic indicate a seawater Mg/Ca of ∼3.3, whereas echinoderms from the Jurassic to the Cretaceous indicate a Mg/Ca of ∼1.4. The present seawater Mg/Ca is ∼5.
French Haemovigilance Data on Platelet Transfusion

The Agence Française de Sécurité Sanitaire des Produits de Santé (Afssaps; French Health Products Safety Agency) is responsible, through its hemovigilance unit, for the organization and the functioning of the national hemovigilance network. In accordance with the French law, it receives all data on adverse transfusion reactions regardless of their severity. With the aim of evaluating the tolerance of two kinds of labile blood products (LBP), pooled platelet concentrates (PP) and apheresis platelet concentrates (APC), we screened the French national database from January 1, 2000 to December 31, 2006. We observed that the number of transfusion incident reports is more than twice as high with APC (8.61:1,000 LBP) than with PP (4.21:1,000 LBP). The difference between these two ratios is statistically significant as shown by chi-square test (e = 21.00 with α= 5%). The risk to suffer adverse reactions of any type, except for alloimmunization, is higher with APC, and the major type of diagnosis related to APC is allergic reaction (1:200 APC issued) even if those allergic reactions are rarely serious. The new French National Hemovigilance Commission should impel a working group evaluating this topic and above all the impact of additive solutions which have been used since 2005 to put forward preventives measures.
Low adiponectin levels are associated with renal cell carcinoma: A case‐control study

Adiponectin is a novel endogenous insulin sensitizer, secreted by mature adipocytes. Circulating levels of adiponectin are inversely associated with obesity and insulin resistance. Because obesity is a risk factor for renal cell carcinoma (RCC), we hypothesized that low adiponectin levels are associated with RCC. To evaluate this hypothesis, we conducted a case‐ control study of 70 patients with histologically confirmed RCC and 280 healthy controls matched by gender, age and county of residence. Study subjects were interviewed and blood samples were collected during a 32‐month period in Athens, Greece. Serum adiponectin levels were statistically, significantly and inversely associated with RCC when compared with controls (OR = 0.76, p = 0.05) and this association remained practically unchanged after controlling for BMI; the introduction of waist to hip ratio along with adiponectin in the multiple logistic regression analysis model rendered the association between adiponectin and RCC risk insignificant, indicating that altered levels of adiponectin may mediate the effect of central or intra‐abdominal obesity on RCC. Prospective studies as well as studies exploring underlying mechanisms are needed to fully explore the role of adiponectin in predicting future risk of RCC in humans. © 2006 Wiley‐Liss, Inc.