Miracle-dz/UniFAR-FTUs huggingface dataset:
The signal sequence of lymphocytic choriomeningitis virus contains an immunodominant cytotoxic T cell epitope that is restricted by both H-2D(b) and H-2K(b) molecules.

Infection of H-2b mice with lymphocytic choriomeningitis virus (LCMV) generates three well-characterized H-2D(b)-restricted immunodominant epitopes delineated in the NP, GP1, and GP2 proteins. Here we report that the H-2D(b)-restricted GP1 epitope GP33-41/43 (KAVYNFATC/GI) located in the signal sequence of LCMV is also the immunodominant epitope recognized by CTL at the surface of the same infected cells in the context of H-2K(b) restriction. The GP1 epitope bound to H-2D(b) and H-2K(b) molecules with comparable affinities. The respective binding processes involved different sets of peptide anchoring residues and required dramatically different conformations of the peptide backbone as well as rearrangement of residue side chains. The 10-mer peptide GP34-43 (AVYNFATCGI) was the optimal H-2K(b)-binding sequence and the 8-mer peptide GP34-41 (AVYNFATC) the minimal sequence for optimal H-2K(b)-restricted CTL recognition. Comparison of lytic activities of primary splenic anti-LCMV CTL from C57BL/6 (D(b+)/K(b+)), B10A. [5R] (D(b-)/K(b+)), and B10A. [2R] (D(b+)/K(b-)) mice against LCMV-infected or peptide-coated target cells expressing either one or the two MHC alleles revealed that the H-2K(b)-restricted component of the anti-GP1 CTL response was mounted independently of but as efficiently as its H-2D(b) counterpart. Analysis of the immune response against a GP1 variant that escapes CTL recognition showed that the GP1 epitope: (i) was likely the only immunodominant LCMV epitope in the context of H-2K(b), and (ii) could efficiently evade H-2D(b) and H-2K(b)-restricted CTL mediated lysis.
Profile And Outcome of Variceal Bleeding Patients Referred for Endoscopy At A Tertiary Hospital in Kedah

Introduction: Variceal bleeding is a major complication of portal hypertension and is a leading cause of death in patients with cirrhosis. Objectives: To determine the prevalence of variceal bleeding and to identify the etiology of cirrhosis. To assess the intervention during endoscopy and to determine the outcome of intervention. Methodology: A retrospective observational study on 95 consecutive patients referred for endoscopy with the first episode of variceal bleeding was conducted in Hospital Sultan Abdul Halim, Kedah from 1 st of January 2013 till 31 st of December 2013. Data was analyzed using Microsoft Excel 2007. Results: Majority of the patients were male, 63(66.3%) and Malay, 63(66.3%). The mean(SD) age was 59.1(10.8) years. Variceal bleeding was highest in the age group of 51 to 60 years old, 36(37.9%). From the endoscopic finding, 69(72.6%) cases were of oesophageal variceal bleeding. Among those with liver cirrhosis, 23(33.3%) were due to hepatitis C. 39(41.1%) patients underwent endoscopic variceal ligation, 4(4.2%) received sclerotherapy and 25(26.3%) received intravenous terlipressin. In-hospital mortality and re-bleeding rate were 2(2.1%) and 10(10.5%) respectively. The median (IQR) hospital stay was 1(1,2) day. Conclusion: Relatively low in-hospital mortality and re-bleeding rates is most probably due to the smaller proportion of patients with severe liver dysfunction and management which adhered to clinical practice guideline.
Mutational analysis and genotype-phenotype correlation of 29 unrelated Japanese patients with X-linked adrenoleukodystrophy.

BACKGROUND X-linked adrenoleukodystrophy (ALD) is an inherited disease characterized by progressive neurologic dysfunction, occasionally associated with adrenal insufficiency. The classic form of ALD usually has onset in childhood (childhood cerebral ALD), with rapid neurologic deterioration leading to a vegetative state. Adult-onset cerebral ALD also presents with rapidly progressive neurologic dysfunction. Milder phenotypes such as adrenomyeloneuropathy and Addison disease only also have been recognized. Despite discovery of the causative gene, a molecular basis for the diverse clinical presentations remains to be elucidated. OBJECTIVES To conduct mutational analyses in 29 Japanese patients with ALD from 29 unrelated families, to obtain knowledge of the spectrum of mutations in this gene, and to study genotype-phenotype correlations in Japanese patients. METHODS The 29 patients comprised 13 patients with childhood cerebral ALD, 11 patients with adult-onset cerebral ALD, and 5 patients with adrenomyeloneuropathy. We conducted detailed mutational analyses of 29 unrelated Japanese patients with ALD by genomic Southern blot analysis and direct nucleotide sequence analysis of reverse transcriptase-polymerase chain reaction products derived from total RNA that was extracted from cultured skin fibroblasts, lymphoblastoid cells, or peripheral blood leukocytes. RESULTS Three patients with adult-onset cerebral ALD were identified as having large genomic rearrangements. The remaining 26 patients were identified as having 21 independent mutations, including 12 novel mutations resulting in small nucleotide alterations in the ALD gene. Eighteen (69%) of 26 mutations were missense mutations. Most missense mutations involved amino acids conserved in homologous gene products, including PMP70, mALDRP, and Pxa1p. The AG dinucleotide deletion at position 1081-1082, which has been reported previously to be the most common mutation in white patients (12%-17%), was also identified as the most common mutation in Japanese patients (12%). All phenotypes were associated with mutations resulting in protein truncation or subtle amino acid changes. There were no differences in phenotypic expressions between missense mutations involving conserved amino acids and those involving nonconserved amino acids. CONCLUSIONS There are no obvious correlations between the phenotypes of patients with ALD and their genotypes, suggesting that other genetic or environmental factors modify the phenotypic expressions of ALD.
A new species of Pharaxonotha (Coleoptera: Erotylidae), probable pollinator of the endangered Cuban cycad, Microcycas calocoma (Zamiaceae)

The new species Pharaxonotha esperanzae (Coleoptera: Cucujoidea: Erotylidae: Pharaxonothinae) is described. It feeds on the pollen of the endangered Cuban cycad Microcycas calocoma (Miq.) A. DC. and breeds in its male cones. Its potential role as a pollinator of Microcycas is discussed. Resumen: Se describe la especie nueva: Pharaxonotha esperanzae (Coleoptera: Cucujoidea: Erotylidae: Pharaxonothinae). Esta se alimenta del polen del cicadal cubano amenazado Microcycas calocoma (Miq.) A.DC y se reproduce en su cono masculino. Se discute su papel potencial como agente polinizador.
Expression of the neuroendocrine cell marker 7B2 in human ACTH secreting tumours

OBJECTIVE AND DESIGN Pro‐opiomelanocortin gene expression is a ubiquitous phenomenon which takes place not only in the pituitary but also in many normal and tumoral non‐pituitary tissues. However, the clinical features of the ectopic ACTH syndrome are rarely encountered. To further investigate this problem we examined series of normal human pltuitaries and endocrine tumours evaluating the tissue content of pro‐oplomelanocortin peptides, and the state of neuroendocrine differentiation as Indicated by the biochemical marker 7B2.
Alternate Technique in Managing Adhesions After Zone 3 Extensor Tendon Repair: A Case Report

Extensor tendon injuries are given less importance than the flexor tendon injuries; however, the extensor mechanism is more complicated than flexor tendon system, and regaining satisfactory function is a challenge. It has been reported that loss of digital flexion would affect grasp and power grip imposing greater functional loss than digital extensor lag. Zone 3 extensor tendon management is complex because of excessive scar formation limiting composite digital flexion and extension. The adhesions are more common if the tendon is immobilized for long period. The purpose of this care report is to describe the alternate technique in managing adhesion after prolong immobilization in zone 3 extensor tendon injuries.
Glutamatergic input governs periodicity and synchronization of bursting activity in oxytocin neurons in hypothalamic organotypic cultures

During suckling, oxytocin (OT) neurons display a bursting electrical activity, consisting of a brief burst of action potentials which is synchronized throughout the OT neuron population and which periodically occurs just before each milk ejection in the lactating rat. To investigate the basis of such synchronization, we performed simultaneous intracellular recordings from pairs of OT neurons identified retrospectively by intracellular fluorescent labelling and immunocytochemistry in organotypic slice cultures derived from postnatal rat hypothalamus. A spontaneous bursting activity was recorded in 65% of OT neurons; the remaining showed only a slow, irregular activity. Application of OT triggered bursts in nonbursting neurons and accelerated bursting activity in spontaneously bursting cells. These cultures included rare vasopressinergic neurons showing no bursting activity and no reaction to OT. Bursts occurred simultaneously in all pairs of bursting OT neurons but, as in vivo, there were differences in burst onset, amplitude and duration. Coordination of firing was not due to electrotonic coupling because depolarizing one neuron in a pair had no effect on the membrane potential of its partner and halothane and proprionate did not desynchronize activity. On the other hand, bursting activity was superimposed on volleys of excitatory postsynaptic potentials (EPSPs) which occurred simultaneously in pairs of neurons. EPSPs, and consequently action potentials, were reversibly blocked by the non‐NMDA glutamatergic receptor antagonist CNQX. Taken together, these data, obtained from organotypic cultures, strongly suggest that a local hypothalamic network governs synchronization of bursting firing in OT neurons through synchronous afferent volleys of EPSPs originating from intrahypothalamic glutamatergic inputs.
IP 3 receptor-dependent Ca 2 release modulates excitation-contraction coupling in rabbit ventricular myocytes

Domeier TL, Zima AV, Maxwell JT, Huke S, Mignery GA, Blatter LA. IP3 receptor-dependent Ca release modulates excitation-contraction coupling in rabbit ventricular myocytes. Am J Physiol Heart Circ Physiol 294: H596–H604, 2008. First published November 30, 2007; doi:10.1152/ajpheart.01155. 2007. — Inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)-dependent Ca signaling exerts positive inotropic, but also arrhythmogenic, effects on excitation-contraction coupling (ECC) in the atrial myocardium. The role of IP3R-dependent sarcoplasmic reticulum (SR) Ca release in ECC in the ventricular myocardium remains controversial. Here we investigated the role of this signaling pathway during ECC in isolated rabbit ventricular myocytes. Immunoblotting of proteins from ventricular myocytes showed expression of both type 2 and type 3 IP3R at levels 3.5-fold less than in atrial myocytes. In permeabilized myocytes, direct application of IP3 (10 M) produced a transient 21% increase in the frequency of Ca sparks (P 0.05). This increase was accompanied by a 13% decrease in spark amplitude (P 0.05) and a 7% decrease in SR Ca load (P 0.05) and was inhibited by IP3R antagonists 2-aminoethoxydiphenylborate (2-APB; 20 M) and heparin (0.5 mg/ml). In intact myocytes endothelin-1 (100 nM) was used to stimulate IP3 production and caused a 38% (P 0.05) increase in the amplitude of action potential-induced (0.5 Hz, field stimulation) Ca transients. This effect was abolished by the IP3R antagonist 2-APB (2 M) or by using adenoviral expression of an IP3 affinity trap that buffers cellular IP3. Together, these data suggest that in rabbit ventricular myocytes IP3R-dependent Ca release has positive inotropic effects on ECC by facilitating Ca release through ryanodine receptor clusters.
T7 Protein Synthesis in F-Factor-Containing Cells: Evidence for an Episomally Induced Impairment of Translation and Its Relation to an Alteration in Membrane Permeability

T7 infection of F-factor-containing PIFA+,B+ cells is abortive. In spite of the presence of mRNA for all three classes of T7 proteins, only the earliest of the T7 proteins are synthesized. A crucial question is whether the failure of T7 to develop in PIFA+,B+ cells is the result of an inability to translate the late classes of T7 mRNA or, as has been recently suggested (Britton, and Haselkorn, 1975; Condit, 1975), whether it is the result of a more generalized alteration in membrane permeability. We have examined the effects of the wild-type PIFA+,B+ episome and two episomal mutations (pifA− and pifB−) on in vitro translation and membrane permeability. In vivo the episomal mutations allow partial or complete T7 development to occur. We demonstrate that cell-free protein-synthesizing systems from T7-infected PIFA+,B+ cells show a three- to fivefold decrease in the rate of translation of both natural and synthetic mRNA. In addition, ribosomes from T7-infected PIFA+,B+ cells are defective in their ability to bind Fmet tRNAf in response to natural mRNA. By contrast, cell-free extracts from T7-infected pifA− (PIFA−,B+) cells retain the ability to bind Fmet tRNAf and to translate natural and synthetic mRNA at normal rates. The defective T7-infected PIFA+,B+ ribosomes can be restored to full activity by a trypsin-sensitive fraction from uninfected PIFA+,B+ or T7-infected PIFA−,B+ cells. Despite the differences in translational capacity of these extracts, both T7-infected PIFA+,B+ and PIFA−,B+ cells display the same permeability lesions as measured by the loss of ATP from the cells into the supernatant. Mutation of the episome to pfiB− prevents the loss of ATP from the cells after T7 infection.
Polypoid Uterine Leiomyosarcomas in a Sheep

Leiomyosarcoma was diagnosed in the uterus surgically removed from a 3-year-old pet Suffolk ewe with a history of bleeding from the vulva, spontaneous lactation, and nursing behavior. The uterus contained multiple well-circumscribed, soft, intraluminal polypoid masses of variable sizes (0.5–4 cm). The masses were red, with white, smooth, and glistening cut surfaces. Histologically they comprised variably dense sheets of moderately pleomorphic, plump spindle cells embedded in richly vascularized stroma. The mitotic index was usually low (0-1/high-power field), but in some polyps there were up to 10 mitoses/high-power field. Neoplastic cells stained positive for alpha smooth muscle actin (α-SMA) by immunohistochemistry. Ultrastructural features of neoplastic cells included the presence of basal lamina, scant microfilaments, contracted nuclei with blunt ends, and flat intercellular junctions. Uterine leiomyosarcoma was diagnosed based on cellular morphology and atypia and positive immunohistochemistry for α-SMA.
Multifocal Motor Neuropathy: Update on Clinical Characteristics, Pathophysiological Concepts and Therapeutic Options

Multifocal motor neuropathy (MMN) is an acquired immune-mediated neuropathy characterized by chronic or stepwise progressive asymmetrical limb weakness without sensory deficits. The upper extremities are more often affected than the lower extremities with distal paresis dominating over proximal paresis. Important diagnostic features are persistent multifocal partial conduction blocks (CBs) and the presence of high-titer anti-GM1 serum antibodies. Motor neuron disease, other chronic dysimmune neuropathies, such as chronic inflammatory demyelinating polyneuropathy and the Lewis-Sumner syndrome (MADSAM neuropathy), are important differential diagnoses. While corticosteroids and plasma exchange are largely ineffective, high-dose intravenous immunoglobulins are regarded as first-line treatment. In spite of significant success in elucidating the underlying disease mechanisms in MMN during the past few years, important pathophysiological issues and the optimum long-term therapy remain to be clarified. The present review summarizes the clinical picture and current pathophysiological concepts of MMN with a special focus on the molecular and electrophysiological basis of CBs and highlights established therapies as well as possible novel treatment options.
Alcohol is longitudinally associated with lower urinary tract symptoms partially via high-density lipoprotein.

BACKGROUND Previous studies on the association of alcohol consumption with lower urinary tract symptoms (LUTS) have been inconsistent, and none took into account the dynamic nature of LUTS, fluctuating over time. The purpose of the study was to determine the longitudinal association of alcohol consumption with LUTS. METHODS We used generalized estimating equations to analyze the longitudinal association of alcohol consumption with LUTS in a longitudinal study of 9,712 healthy men 30 years or older who visited our institution multiple times for routine comprehensive health evaluations, with an average follow-up period of 27.9 months. RESULTS Light-moderate alcohol consumption (0.1 to 29 g/d) was associated with decreased likelihood of moderate-severe LUTS, whereas heavy alcohol consumption (≥30 g/d) was associated with increased likelihood of moderate-severe LUTS in a dose-dependent manner. Compared to those with 0 g/d alcohol intake, subjects who drank 0.1 to 9.9, 10 to 19.9, 20 to 29.9, 30 to 39.9, or ≥40 g/d of alcohol were in general significantly associated with moderate-severe LUTS with adjusted odds ratio (95% confidence interval) as follows respectively: 0.94 (0.87 to 1.02), 1.00 (0.91 to 1.09), 0.85 (0.77 to 0.93), 1.08 (0.98 to 1.19), and 1.31 (1.19 to 1.44). However, the protective association of light-moderate alcohol consumption with LUTS was greatly attenuated when serum high-density lipoprotein (HDL) was added to the analysis, specifically for voiding symptoms. CONCLUSIONS We show strong evidence there is longitudinal association of alcohol consumption with LUTS. The protective effect of light-moderate alcohol consumption on LUTS is in part modulated by HDL as a confounder, similar to its effect on coronary heart disease.
Clay sources for Meroitic finewares

L'objectif de cette etude est l'observation de lames minces et l'analyse chimique de ceramiques meroitiques afin de determiner si les poteries ont ete fabriquees au nord de la Nubie, au sud, ou dans les deux regions, et ainsi de demontrer l'existence d'un commerce entre l'une et l'autre de ces contrees.
Noncredible Psychiatric and Cognitive Symptoms in a Workers' Compensation “Stress” Claim Sample

Information is lacking regarding the prevalence of fraudulent psychiatric and cognitive symptoms in the “stress” claim workers' compensation population. Using various validity indices (Negative Impression Scale, the Malingering Index, and the Rogers Discriminant Function) of the Personality Assessment Inventory (PAI), between 9 and 29% of 233 workers' compensation “stress” claim litigants were identified as exhibiting noncredible psychiatric symptoms. In addition, 15% of the subjects were determined to have noncredible cognitive symptoms on the Dot Counting Test, although only 8% displayed suspect effort on the 15-Item Memorization Test, with 5% of subjects failing both cognitive effort tests. The percentage of positive identifications on both a PAI and cognitive credibility index ranged from only 2 to 4%. Further, correlations between PAI validity indices and cognitive effort scales were nonexistent to modest, indicating that the psychiatric and cognitive credibility indices are measuring different aspects of noncredible symptom production. It was predicted that the PAI profiles of the participants displaying suspect cognitive symptoms would be elevated on the Somatic Concerns, Antisocial, and/or Borderline scales; however, elevations (relative to subjects with credible cognitive performance) were instead noted on the Somatic Concerns, Depression, Anxiety, Anxiety-Related Disorders, and Schizophrenia scales.
Diagnosis of Recanalization of the Intracranial Artery Has Poor Inter-Rater Reliability

BACKGROUND AND PURPOSE: Recanalization is the important outcome measure for acute stroke therapy. Several methods of recanalization assessment are used in clinical practice, but few studies have addressed their reliability. We, therefore, sought to assess interobserver reliability of the diagnosis of intracranial artery recanalization following intervention by using TIMI criteria. MATERIALS AND METHODS: The digital angiography scans of all patients with acute ischemic stroke during 2009 undergoing DSA and endovascular procedures at Ostrava University Hospital were assessed in the study. Images were retrospectively evaluated for intracranial artery recanalization on the TIMI scale by 2 experienced neuroradiologists who were blinded to clinical findings and to each other. RESULTS: The angiography scans of 43 patients (16 females; age, 70.5 ± 14 years; median baseline NIHSS score, 15 [IQR, 11–18]) were retrospectively evaluated in our study. At 3 months, 27% of patients had mRS scores ≤ 2 and mortality was 18%. Two radiologists diagnosed TIMI grades as follows: TIMI 0, 16%, and 16%; TIMI 1, 21%, and 8%; TIMI 2a, 32% and 29%; TIMI 2b, 13% and 16%; TIMI 3, 18, and 31%. Interobserver agreement for recanalization was weighted κ = 0.4 (95% CI, 0.2–0.6). CONCLUSIONS: The diagnosis of recanalization after interventional procedures was found to have poor interobserver agreement between 2 experienced neuroradiologists. TIMI criteria, therefore, do not permit reliable comparison of the efficacy of recanalization therapy among different studies.
Evolution of Peptidase Diversity*

A wide variety of peptidases associate with vital biological pathways, but the origin and evolution of their tremendous diversity are poorly defined. Application of the MEROPS classification to a comprehensive set of genomes yields a simple pattern of peptidase distribution and provides insight into the organization of proteolysis in all forms of life. Unexpectedly, a near ubiquitous core set of peptidases is shown to contain more types than those unique to higher multicellular organisms. From this core group, an array of eukaryote-specific peptidases evolved to yield well known intracellular and extracellular processes. The paucity of peptidase families unique to higher metazoa suggests gains in proteolytic network complexity required a limited number of biochemical inventions. These findings provide a framework for deeper investigation into the evolutionary forces that shaped each peptidase family and a roadmap to develop a timeline for their expansion as an interconnected system.
What Matters in the Results of Repeated Intravenous Thrombolysis for Recurrent Ischemic Stroke?

val 225 days and 45.9% female. Heavier severity and worse functional outcome were observed in the RT group, but the difference of intracranial hemorrhages (ICHs) from 2 events did not reach statistical significance. More ICHs occurred in RTs with prior stroke within last 30 days than those in chronic stroke phase in a subgroup analysis (25.0–4.9%, p = 0.018). Only National Institutes of Health Stroke Scale (NIHSS) was significantly associated with a good functional outcome (OR 0.921, 95% CI 0.857–0.990) and ICH (OR 1.177, 95% CI 1.031–1.344) in the logistic regression analysis. Our literature review indicated that baseline stroke severity was the main predictor of the functional outcome and ICH Dear Sir, We read with interest the article by Laible et al. [1] regarding repeated thrombolysis (RT) for acute ischemic stroke (AIS). Although this study has attempted to address the efficacy and safety issue of RT, we strongly feel that one should be cautious in understanding the conclusion. Since the data of onset-to-treatment time were not collected in 33.3% cases and the sample size was also small, the conclusion cannot be considered powerful and authentic. We conducted a systemic literature review in PubMed up to December, 2015. A total of 15 studies [1–15] involving 57 cases and 61 RTs were collected. The details are shown in the ( table 1 ). The median age was 73 at the first event, the median time interReceived: December 22, 2015 Accepted: February 5, 2016 Published online: March 8, 2016