Miracle-dz/UniFAR-FTUs huggingface dataset:
Subnuclear targeting of Runx1 Is required for synergistic activation of the myeloid specific M‐CSF receptor promoter by PU.1

Many types of acute myelogenous leukemia involve chromosomal translocations that target the C‐terminus of Runx1/AML1 transcription factor, a master regulator of hematopoiesis. The C‐terminus of Runx1/AML1 that includes the nuclear matrix targeting signal (NMTS) is essential for embryonic development, hematopoiesis, and target gene regulation. During the onset and normal progression of hematopoiesis, several lineage‐specific factors such as C/EBPα and PU.1 interact with Runx1 to regulate transcription combinatorially. Here we addressed the functional interplay between subnuclear targeting of Runx1 and gene activation during hematopoiesis. Point mutations were generated in the NMTS of the human Runx1 protein and tested for their effect on transcriptional cooperativity with C/EBPα and PU.1 at myeloid‐specific promoters. We characterized five mutants that do not alter nuclear import, DNA binding or C/EBPα‐dependent synergistic activation of the target gene promoters. However a critical tyrosine in the NMTS is required for subnuclear targeting and activation of the granulocyte‐macrophage colony stimulating factor (GM‐CSF) promoter. Furthermore, this point mutation is defective for transcriptional synergism with PU.1 on the macrophage colony stimulating factor (MCSF) receptor c‐FMS promoter. Our results indicate that the NMTS region of Runx1 is required for functional interactions with PU.1. Taken together, our findings establish that subnuclear targeting of Runx1 is a critical component of myeloid‐specific transcriptional control. © 2005 Wiley‐Liss, Inc.
Toxicity of new emerging pollutant tris‐(2,3‐dibromopropyl) isocyanurate on BALB/c mice

The emerging heterocyclic brominated flame retardant tris‐(2,3‐dibromopropyl) isocyanurate (TBC), widely used in reinforced plastics, has demonstrated toxicity to fish. However, little is known about its toxicity in rodents. This study aims to determine the effect of TBC on growth, biochemical parameters in serum, organs and related gene expression of both male and female BALB/c mice after gastro‐gavage administration of 0, 2, 10 and 50 mg kg−1 TBC for 28 days. Results indicated that exposure to TBC had no effects on basic growth and food intake of mice, but significantly increased serum alanine aminotransferase levels in male mice. Histopathological analyses showed that focal necrosis (2, 10 and 50 mg kg−1 TBC‐exposed groups) and ballooning degeneration (10 and 50 mg kg−1 TBC‐exposed groups) were found in mouse liver, whereas transmission electron microscopy revealed dose‐dependent hepatocyte apoptosis, mitochondrial degeneration and endoplasmic reticulum dilation. Histopathological and ultrastructural assessments in the lung showed dose‐dependent hyperplasia of pulmonary alveolar epithelium, bronchial congestion, infiltration of inflammatory cells and mitochondrial swelling following TBC exposure. Our results also indicated that mitochondria are one of the major target cytoplasmic organelles for TBC, suggesting that damage in mitochondria is one of the pathways that led to toxic effects in the liver and lung of TBC‐treated groups. Moreover, TBC effectively activated the gene expression of p53 in mice liver. Our findings provide strong evidence that TBC induces significant toxicity in mice organs, especially in liver and lung, which play vital roles in detoxification and gas exchange, respectively. This research will contribute to characterize the toxic effects of TBC, which was introduced as one of the candidates for brominated flame retardant replacement. Copyright © 2014 John Wiley & Sons, Ltd.
Identification of two biologically distinct strains of transmissible mink encephalopathy in hamsters.

Experimental transmission of the Stetsonville, Wisconsin, U.S.A. source of transmissible mink encephalopathy (TME) to outbred Syrian golden hamsters resulted in two distinct syndromes, termed hyper (HY) and drowsy (DY), that diverge by the third hamster passage. The syndromes differed with respect to clinical signs, incubation period, brain titre, brain lesion profile and pathogenicity in mink. HY hamster TME had an incubation period of 65 +/- 1 days and was characterized by clinical signs of hyperaesthesia and cerebellar ataxia. Lethargy and the absence of hyperexcitability or cerebellar ataxia were representative of DY hamster TME which had an incubation period of 168 +/- 2 days. At endstage, HY and DY infected animals had brain titres of 10(9.5) LD50/g and 10(7.4) LD50/g of tissue, respectively, indicating that the replication kinetics of these two strains is different. Hamster TME passaged back into mink revealed that only DY retained mink pathogenicity. This suggests that the DY agent is the major mink pathogen in the Stetsonville TME source that is also pathogenic in hamsters after a long incubation period. The HY agent is likely to be a minor component of the original TME mink brain that replicates more rapidly than DY agent in hamsters, but alone is non-pathogenic in mink. The presence of the HY and DY strains of agent that retain their biological characteristics on repeated hamster passage in the Stetsonville TME source requires that the informational molecule encoding these transmissible agents has the capacity to account for this biological diversity.
Potential role of the anterior cingulate cortex in PTSD: Review and hypothesis

Many symptoms of PTSD represent conditioned responses to stimuli associated with a traumatic experiences. In this review, we propose that the anterior cingulate—a brain region that appears to be involved in fear‐conditioning—is dysfunctional in PTSD, thus facilitating exaggerated emotional and behavioral responses (hyperarousal) to conditioned stimuli. Preclinical studies suggest that the anterior cingulate may serve a critical gating function in modulating conditioned fear responses. As such, this region would be a key component of a neural circuit involved in the pathophysiology of PTSD. An amygdala‐locus coeruleus‐anterior cingulate circuit may be consistent with evidence for chronic noradrenergic activation documented in PTSD patients. According to this model, efferent noradrenergic projections from the locus coeruleus may dampen anterior cingulate function. This in turn would allow myriad external or internally driven stimuli to produce the exaggerated emotional and behavioral responses characteristic of PTSD. If confirmed in future research, cingulate dysfunction would have important theoretical and treatment implications. Depression and Anxiety 9:1–14, 1999. Published 1999 Wiley‐Liss, Inc.
G-CSF (Granulocyte-Colony Stimulating Factor) in the Central Nervous System

G-CSF (Granulocyte-colony stimulating factor) is a hematopoietic growth factor that has been known for 20 years, and has been named for its role in the proliferation and differentiation of cells of the myeloic lineage. We have uncovered a novel spectrum of activities of G-CSF in the central nervous system. G-CSF and its receptor are expressed by neurons in many brain regions, and are upregulated upon experimental stroke. In neurons, G-CSF acts anti-apoptotically by activating several protective pathways. In vivo, G-CSF decreases infarct volumes in acute stroke models in rodents. Moreover, G-CSF stimulates neuronal differentiation of adult neural stem cells in the brain, and improves long-term recovery in more chronic stroke models. Thus, G-CSF is a novel neurotrophic factor, and a highly attractive candidate for the treatment of neurodegenerative conditions. Here we discuss this new property of G-CSF in contrast to its known functions in the hematopoietic system, summarize data from other groups on G-CSF’s actions in cerebral ischemia, compare G-CSF to Erythropoietin (EPO) in the CNS and highlight clinical implications.
Cutoff value of carcinoembryonic antigen and carbohydrate antigen 19-9 elevation levels for monitoring recurrence in patients with resectable gastric adenocarcinoma.

BACKGROUND The aim of this longitudinal study was to try and improve the specificity of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in monitoring tumor recurrence in patients with resectable gastric adenocarcinoma by setting suitable elevation levels. METHODS One hundred eighty-one patients with resectable gastric adenocarcinoma were considered. Serum samples were obtained preoperatively and every 3 months postoperatively. RESULTS Preoperative CEA and CA19-9 positivity rates were 19.9% and 18.2%. The specificity and sensitivity of CEA elevation to monitor recurrence were 92.9% and 23.4% versus 76.5% and 78.9% in CEA-negative versus CEA-positive patients, respectively. For CA19-9 the specificity and sensitivity were 95.0% and 18.8% versus 60.0% and 83.3% in CA19-9-negative versus CA19-9-positive patients, respectively. When we set the elevation level of CEA at 5 ng/mL, the specificity of CEA elevation to monitor recurrence increased to 94.1% for CEA-positive patients. The specificity increased to 93.3% for CA19-9-positive patients when the CA19-9 elevation level was set at 100 U/mL. CONCLUSIONS For CEA- or CA19-9-positive patients with resectable gastric adenocarcinoma we can increase the specificity of CEA and CA19-9 by setting the elevation level of CEA at 5 ng/mL and CA19-9 at 100 U/mL.
An Appraisal of Personal Income Tax Evasion in Nigeria

The objective of this study is to appraise the evasion of personal income tax in Nigeria. A total of 160 questionnaires were administered to some selected self-employed individuals in Edo State comprising businessmen, contractors, professional practitioners like lawyers, doctors, accountants, architects and traders in shops as well as staff of Federal Inland Revenue Service in Benin City, Edo State, Nigeria. The result revealed that the tax payers’ relationship with tax authority (TAXPAY_TAXAUTH) and weak penalties (PENALTIES) have a significant influence on tax evasion in Nigeria. Tax rate showed a positive relationship with tax evasion. This means that the higher the tax rate the higher the tendency of tax evasion. The Board should intensify tax payer education and maintain a harmonious relationship capable of fostering voluntary compliance. In addition, efforts should be made towards entrenching stiff penalties for evaders. Finally the prevailing tax rates should be reviewed optimally as not to serve as disincentives to compliance.
Neonatal sepsis: high antibiotic resistance of the bacterial pathogens in a neonatal intensive care unit in Karachi.

OBJECTIVE To study the bacterial pathogens causing neonatal sepsis and their sensitivity pattern so that guidelines can be prepared for empirical antibiotic therapy. SETTING The study was conducted in the neonatal intensive care unit (NICU) at PNS Shifa (Naval Hospital), Karachi during January 1997 to June 1999. METHODS Blood specimens for culture were drawn from 520 newborns admitted in a NICU with sepsis. The specimens were inoculated into brain heart infusion broth. Subcultures were performed on days 1, 2, 3, 5, 7 and 10. The isolates were identified by standard biochemical tests. Antibiotic resistance pattern of the isolates was studied by Modified Kirby Baur disc diffusion technique. RESULTS A total of 212 organisms were isolated. These included Staphylococcus aureus (n = 65), Klebsiella pneumoniae (n = 73), Acinetobacter baumannii (n = 23), Escherichia coli (n = 22), Enterobacter cloacae (n = 18), Citrobacter diversus (n = 5), Pseudomonas aeruginosa (n = 4) and group B Streptococcus (n = 2). On antibiotic sensitivity testing, 61.54% of Staphylococcus aureus isolates were found to be methicillin resistant. Susceptibility to the other common drugs was also quite low while 89.23% of these were susceptible to amikacin and 100% to vancomycin. More than 90% gram negative rods were resistant to ampicillin and co-trimoxazole. Resistance to gentamicin was as high as 90.4% for Klebsiella pneumoniae; 60.87% for Acinetobacter baumannii. Resistance to the third generation cephalosporins and the quinolone tested (ciprofloxacin) varied between 25-75%. Majority of the isolates were susceptible to meropenem and amikacin. CONCLUSION In view of the isolation of highly antibiotic resistant organisms, vancomycin in combination with amikacin or a carbapenem is the drug of choice for empirically treating neonatal sepsis.
In silico directed mutagenesis identifies the CD81/claudin-1 hepatitis C virus receptor interface

Hepatitis C virus (HCV) entry is dependent on host cell molecules tetraspanin CD81, scavenger receptor BI and tight junction proteins claudin‐1 and occludin. We previously reported a role for CD81/claudin‐1 receptor complexes in HCV entry; however, the molecular mechanism(s) driving association between the receptors is unknown. We explored the molecular interface between CD81 and claudin‐1 using a combination of bioinformatic sequence‐based modelling, site‐directed mutagenesis and Fluorescent Resonance Energy Transfer (FRET) imaging methodologies. Structural modelling predicts the first extracellular loop of claudin‐1 to have a flexible beta conformation and identifies a motif between amino acids 62–66 that interacts with CD81 residues T149, E152 and T153. FRET studies confirm a role for these CD81 residues in claudin‐1 association and HCV infection. Importantly, mutation of these CD81 residues has minimal impact on protein conformation or HCVglycoprotein binding, highlighting a new functional domain of CD81 that is essential for virus entry.
Classification and identification of Actinobacillus actinomycetemcomitans and haemophilus aphrophilus by cluster analysis and deoxyribonucleic acid hybridizations.

Fifteen gram-negative, saccharolytic rods isolated from advanced periodonlal pockeis were compared to type and reference strains of Arlinohacillus actinomycetemcomitans, Haemaphilus aphrophilus, and reference strains of Haemophilus paraphrophilus. Phenotypic features of organisms were used in cluster analysis and multidimensional scaling. Deoxyribonucleic acid (DNA) was extracted from all strains and moles percent guanine plus cytosine content determined. DNA/DNA homology experiments were performed between reference strains of each species and oral isolates. Five strains from periodontosis lesions, two strains from Papillon-Lefevre periodontal lesions, and four strains from periodontitis pockeis of adults were similar to A. actinomycetemcomitans by cluster analyses and by DNA/DNA homologies. Except for a single H. paraphrophilus isolate, the H. aphrophilus and H, paraphrophilus isolates could not be distinguished as two distinct species as there was overlap in biochemical characteristics and DNA/DNA homology. Two strains isolated from periodontosis lesions, two strains from adult periodontilis sites, and three oral reference strains were very similar to each other and to the H. aphrtiphilus type strain using phenotypic features. Hydrogen peroxide decomposition was not found to be a consistent feature of A. actinomycetemcumitans strains isolated from periodontal pockets.
Chronic treatment of rats with sodium valproate downregulates frontal cortex NF-kappaB DNA binding activity and COX-2 mRNA.

OBJECTIVES Valproic acid (VPA) is used to treat bipolar disorder, but its mechanism of action is not clear. VPA shares many cellular and molecular targets with lithium, including reducing arachidonic acid turnover in rat brain phospholipids and cyclooxygenase-2 (COX-2) protein level and activity in rat brain. METHODS We examined the effect of chronic VPA administration (200 mg/kg body weight for 30 days) to produce therapeutically relevant plasma concentrations, on transcription factors (NF-kappaB, AP-1, AP-2, C/EBP, CREB, and ETS) that are known to regulate the COX-2 gene. RESULTS Chronic VPA significantly increased AP-1 DNA binding activity and decreased NF-kappaB DNA binding activity, p50 subunit protein and mRNA expression of COX-2 in frontal cortex compared with untreated control rats. It did not alter AP-2, C/EBP, ETS or CREB DNA binding activity. CONCLUSIONS VPA downregulates NF-kappaB DNA binding activity, likely by decreasing the p50 protein levels. This effect may explain its downregulation of COX-2 mRNA. The decrease in NF-kappaB activity by chronic VPA may affect other NF-kappaB-regulated genes and may be related to VPA's action in bipolar disorder. Chronic VPA may decrease the reported increased brain NF-kappaB components in bipolar patients.
The rate of bone mineral loss in normal men and the effects of calcium and cholecalciferol supplementation.

OBJECTIVE To determine the rate of bone loss in normal men, and to examine the effects of dietary calcium and cholecalciferol supplementation on bone loss in men. DESIGN Double-blinded, placebo-controlled 3-year trial of supplementation with calcium (1000 mg/d) and cholecalciferol (25 micrograms/d). SETTING Clinical research center at a university medical facility. SUBJECTS Normal men 30 to 87 years old, recruited from the Portland community. MEASUREMENTS AND MAIN RESULTS Radial bone mineral content (assessed by single-photon absorptiometry) fell by 1.0%/y (95% CI, -1.3% to 0.7%) at a proximal radial site and 1.0%/y (95% CI, -1.4% to -0.6%) at a distal radial site. Vertebral bone mineral content (assessed by dual-energy quantitative computed tomography) declined by 2.3%/y (95% CI, -2.8% to -1.8%). In these healthy men with a high basal dietary calcium intake (1159 mg/d), calcium and cholecalciferol supplementation did not affect bone loss at any site. CONCLUSIONS Normal men experience a substantial bone loss at both axial and appendicular sites that is not prevented by calcium and vitamin D supplementation in a well-nourished population.
Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014

OBJECTIVE To describe antimicrobial resistance patterns for healthcare-associated infections (HAIs) that occurred in 2011–2014 and were reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network. METHODS Data from central line–associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonias, and surgical site infections were analyzed. These HAIs were reported from acute care hospitals, long-term acute care hospitals, and inpatient rehabilitation facilities. Pooled mean proportions of pathogens that tested resistant (or nonsusceptible) to selected antimicrobials were calculated by year and HAI type. RESULTS Overall, 4,515 hospitals reported that at least 1 HAI occurred in 2011–2014. There were 408,151 pathogens from 365,490 HAIs reported to the National Healthcare Safety Network, most of which were reported from acute care hospitals with greater than 200 beds. Fifteen pathogen groups accounted for 87% of reported pathogens; the most common included Escherichia coli (15%), Staphylococcus aureus (12%), Klebsiella species (8%), and coagulase-negative staphylococci (8%). In general, the proportion of isolates with common resistance phenotypes was higher among device-associated HAIs compared with surgical site infections. Although the percent resistance for most phenotypes was similar to earlier reports, an increase in the magnitude of the resistance percentages among E. coli pathogens was noted, especially related to fluoroquinolone resistance. CONCLUSION This report represents a national summary of antimicrobial resistance among select HAIs and phenotypes. The distribution of frequent pathogens and some resistance patterns appear to have changed from 2009–2010, highlighting the need for continual, careful monitoring of these data across the spectrum of HAI types. Infect Control Hosp Epidemiol 2016;1–14
Renal ammoniagenic response to chronic acid loading: role of glucocorticoids.

Adrenalectomized (ADX) animals exhibit a blunted renal response to chronic acid loading. To determine whether this response truly reflects impaired renal ammoniagenesis from glutamine, urinary ammonium excretion was compared with acid intake in ADX, intact, and ADX rats supplemented with either a low dose (4 micrograms.100 g-1.day-1) or a high dose (40 micrograms.100 g-1.day-1) of triamcinolone. ADX rats consumed similar amounts of acid as did intact controls yet excreted only 37% of the load as ammonium; in contrast intact controls returned 86% and triamcinolone-supplemented animals returned 98 and 88% for low and high doses, respectively. Nor could the reduced ammonium excretion be attributed to increased renal venous release, since total ammonia production, the sum of renal venous and urine ammonium, was reduced to 49% of the intact controls; low- and high-dose triamcinolone restored and markedly increased the production rate. Underlying the impaired ammonia production rate in ADX rats was a reduced rate of glutamine extraction, 350 +/- 49 vs. 896 +/- 102 and 1,260 +/- 247 and 1,448 +/- 112 nmol.min-1.100 g-1 for intact and low and high doses, respectively. Unlike intact acidotic and glucocorticoid-supplemented ADX acidotic rats, glutamine extraction was disassociated from the delivered glutamine load consonant with the role of glucocorticoid in coupling cellular glutamine transport to its metabolic utilization.
Investigation of PMU Performance Under TVE criterion

Phasor measurement unit (PMU) is an emerging measurement technology for power grids which enables the synchronised high speed measurement with precise time stamps for accurate system comparison over a wide geographic area. PMU measurement quality is the key issue in application purposes. To evaluate the measurement quality, the concepts of total vector error (TVE) and benchmark tests, including the magnitude, phase and frequency step tests, are proposed in the C37.118 standard. It also includes requirements for test results. This paper reports the results of tests performed on several PMUs. These tests include both steady state and dynamic conditions conforming to the new requirements under development by the IEEE for the updated C37.118 standard. In addition to validating the new IEEE requirements with actual PMU measurements, the results evaluated by TVE are discussed and with errors analyzed based on phasor magnitude and angle.