Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin‐mediated modulation of cytochrome P450 gene induction profiles in primary rat hepatocyte cultures

In this investigation, we examined the effects of insulin on gene induction responsiveness in primary rat hepatocytes. Cells were cultured for 72 hours either in the absence or presence of 1 μM insulin and then exposed to increasing concentrations of phenobarbital (PB; 0.01–3.5 mM). Culturing in the absence of insulin produced 1.5–2‐fold increases in the induction magnitude of CYP2B1 and CYP2B2 mRNA expression resulting from PB exposures, without altering the bell‐shaped dose‐response curve characteristic of this agent. However, for the CYP3A1 gene, insulin removal led to a pronounced shift in both the PB‐induction magnitude and dose‐response relationships of the induction response, with higher levels of CYP3A1 expression resulting from exposures to lower concentrations of inducer. Insulin removal also reduced the time required to attain maximal induction of CYP2B1/2 and CYP3A1 gene expression. The insulin effects were not specific for PB induction, as insulin deprivation similarly enhanced both dexamethasone‐ and β‐naphthoflavone‐inducible CYP3A1 and CYP1A1 expression profiles, respectively. In contrast, the level of albumin mRNA expression was reduced considerably in cells deprived of insulin. We conclude that insulin is an important regulator of inducible and liver‐specific gene expression in primary rat hepatocytes. © 1998 John Wiley & Sons, Inc. J Biochem Toxicol 13: 1–9, 1999
Stat3 Is Present in the Developing and Adult Rat Cerebellum and Participates in the Formation of Transcription Complexes Binding DNA at the sis‐Inducible Element

Abstract: Stat3 is a member of a recently identified family of proteins named STATs for their ability to act as signal transducers and activators of transcription. Stimulation of epidermal growth factor or cytokine receptors can cause activation of Stat3 and transduction of specific responses to the nucleus. Here the presence of Stat3 has been examined in the rat cerebellum at different times during postnatal development and adulthood by means of immunohistochemistry and western blotting. In addition, DNA binding activity at the sis‐inducible element that is present in the promoter of the c‐fos gene has been studied by electrophoretic mobility shift assay. The results have shown that Stat3 p92 is abundant in the rat cerebellum. Stat3 was found in the external granule cell layer and also within the molecular layer from postnatal day (P) 0 to P7. From P15 to the adult, the internal granule cell layer and Purkinje cells were also stained for Stat3. Nuclear extracts were found to contain DNA binding activity to the sis‐inducible element during development and adulthood. Supershift assays demonstrated that Stat3 mediates the formation of one protein‐DNA complex. The present results suggest that Stat3 participates in intracellular signaling and is involved in maintaining basal c‐fos expression in the cerebellum of the developing and adult rat under physiological conditions.
megasat: automated inference of microsatellite genotypes from sequence data

megasat is software that enables genotyping of microsatellite loci using next‐generation sequencing data. Microsatellites are amplified in large multiplexes, and then sequenced in pooled amplicons. megasat reads sequence files and automatically scores microsatellite genotypes. It uses fuzzy matches to allow for sequencing errors and applies decision rules to account for amplification artefacts, including nontarget amplification products, replication slippage during PCR (amplification stutter) and differential amplification of alleles. An important feature of megasat is the generation of histograms of the length–frequency distributions of amplification products for each locus and each individual. These histograms, analogous to electropherograms traditionally used to score microsatellite genotypes, enable rapid evaluation and editing of automatically scored genotypes. megasat is written in Perl, runs on Windows, Mac OS X and Linux systems, and includes a simple graphical user interface. We demonstrate megasat using data from guppy, Poecilia reticulata. We genotype 1024 guppies at 43 microsatellites per run on an Illumina MiSeq sequencer. We evaluated the accuracy of automatically called genotypes using two methods, based on pedigree and repeat genotyping data, and obtained estimates of mean genotyping error rates of 0.021 and 0.012. In both estimates, three loci accounted for a disproportionate fraction of genotyping errors; conversely, 26 loci were scored with 0–1 detected error (error rate ≤0.007). Our results show that with appropriate selection of loci, automated genotyping of microsatellite loci can be achieved with very high throughput, low genotyping error and very low genotyping costs.
Analisis Pengaruh Instrumen Moneter Syariah Dan Konvensional Terhadap Penyaluran Dana Ke Sektor Pertanian Di Indonesia

This study aimed to analyze the effect of sharia and conventional monetary instruments to the distribution of agricultural sector funds from 2009 to 2014 and using VAR / VECM which analysed through Impulse response Function (IRF) and the Forecast Error Variance Decomposition (FEVD). Results of research on the conventional models, shows that the SBI interest rate and lending interest rates (SBK) significantly negative effect and interbank rates (PUAB) have a significant positive effect on agricultural credit. In addition, the results of research on the sharia model indicates that the SBIS and ERP significant negative effect on agricultural financing and PUAS significant negative effect on agricultural finance. Based on the FEVD results , SBI has a considerable effect on the agricultural credit compared with SBK and interbank rates (PUAB) on the conventional models whereas the models of sharia, SBIS have a smaller effect than the ERP and PUAS. Keywords: agricultural credit and agricultural financing, sharia and conventional monetary instruments, VECM
A Clinical Grading Scale to Predict Malignant Hyperthermia Susceptibility

Background:The diagnosis of an acute malignant hyperthermia reaction by clinical criteria can be difficult because of the nonspecific nature and variable incidence of many of the clinical signs and laboratory findings. Development of a standardized means for estimating the qualitative likelihood of malignant hyperthermia in a given patient without the use of specialized diagnostic testing would be useful for patient management and would promote research into improved means for diagnosing this disease. Methods:Using the Delphi method and an international panel of 11 experts on malignant hyperthermia, a multifactor malignant hyperthermia clinical grading scale comprising standardized clinical diagnostic criteria was developed for classification of existing records and for application to new patients. Results:This scale ranks the qualitative likelihood that an adverse anesthetic event represents malignant hyperthermia (malignant hyperthermia event rank) and that, with further investigation of family history, an individual patient will be diagnosed as malignant hyperthermia susceptible (malignant hyperthermia susceptibility rank). The assigned rank represents a lower bound on the likelihood of malignant hyperthermia. The clinical grading scale requires the anesthesiologist to judge whether specific clinical signs are appropriate for the patient's medical condition, anesthetic technique, and surgical procedure. Conclusions:The malignant hyperthermia clinical grading scale is recommended for use as an aid to the objective definition of this disease. Its use may improve malignant hyperthermia research by allowing comparisons among well-defined groups of patients. This clinical grading system provides a new and comprehensive clinical case definition for the malignant hyperthermia syndrome.
Sleep deprivation potentiates HPA axis stress reactivity in healthy adults.

OBJECTIVE This article describes an experiment that was designed to investigate the effects of sleep deprivation on physiological stress responses in healthy adults. METHOD Twenty-six participants, ages 22-49, completed a 3-night laboratory experiment with randomization to one night of sleep-deprivation or a normal-sleep control condition. After a night of baseline sleep, 12 participants were sleep deprived and 14 were not. After the sleep manipulation, each participant completed the Trier Social Stress Test, a task that requires delivering a speech and performing difficult arithmetic in front of a stern, three-person panel. The stressor was administered from 5:00 p.m. -5:30 p.m. and saliva samples were collected 20 and 5 min before (baseline) and 5, 20, and 40 min after the stressor. Samples were assayed for cortisol (a biomarker for the HPA axis) and alpha-amylase (a putative biomarker for the sympatho-adrenal medullar system). RESULTS Sleep deprivation was associated with higher cortisol levels at baseline (p < .0001) and an amplified cortisol response to the stressor relative to control participants (pinteraction = 0.0039). Alpha-amylase showed a significant main effect of the stressor (p = .0026), but there was no effect of sleep loss at baseline or in response to the stressor. CONCLUSIONS Sleep deprivation is associated with both elevated resting cortisol release and with an exaggerated cortisol response to a stressor indicative of elevated HPA axis responses in healthy adults. Individual differences in the magnitude of this response may represent a risk factor for psychological and physical health consequences associated with heightened cortisol exposure.
Hypercoagulability in End-Stage Liver Disease: Prevalence and Its Correlation With Severity of Liver Disease and Portal Vein Thrombosis

Contrary to well-recognized bleeding diathesis in chronic liver disease, thrombotic events can occur in these patients due to reduction or loss of synthesis of anticoagulant proteins. Forty-seven consecutive patients with end-stage liver disease (ESLD) were investigated for activity of protein C, protein S, antithrombin, and factor V Leiden mutation. Forty-two (89.4%) patients had low levels of at least 1 while 33 (70.2%) patients were deficient for all anticoagulant proteins studied. Forty-six (97.9%) patients were negative for factor V Leiden mutation. The deficiencies were more marked in hepatitis C virus–positive patients and patients with model for end-stage liver disease (MELD) score >15. Six (12.8%) patients had portal vein thrombosis (PVT), and all had diminished protein S activity. In conclusions, deficiency of anticoagulant proteins occur in early phase of chronic liver disease. The severity of deficiency is proportional to the severity of liver disease. Despite the high prevalence of hypercoagulability, the incidence of PVT is low. Further studies with larger cohort of patients are needed to support these conclusions and to study other associated factors.
Induction of the Nitrate Assimilation nirA Operon and Protein-Protein Interactions in the Maturation of Nitrate and Nitrite Reductases in the Cyanobacterium Anabaena sp. Strain PCC 7120

ABSTRACT Nitrate is widely used as a nitrogen source by cyanobacteria, in which the nitrate assimilation structural genes frequently constitute the so-called nirA operon. This operon contains the genes encoding nitrite reductase (nirA), a nitrate/nitrite transporter (frequently an ABC-type transporter; nrtABCD), and nitrate reductase (narB). In the model filamentous cyanobacterium Anabaena sp. strain PCC 7120, which can fix N2 in specialized cells termed heterocysts, the nirA operon is expressed at high levels only in media containing nitrate or nitrite and lacking ammonium, a preferred nitrogen source. Here we examined the genes downstream of the nirA operon in Anabaena and found that a small open reading frame of unknown function, alr0613, can be cotranscribed with the operon. The next gene in the genome, alr0614 (narM), showed an expression pattern similar to that of the nirA operon, implying correlated expression of narM and the operon. A mutant of narM with an insertion mutation failed to produce nitrate reductase activity, consistent with the idea that NarM is required for the maturation of NarB. Both narM and narB mutants were impaired in the nitrate-dependent induction of the nirA operon, suggesting that nitrite is an inducer of the operon in Anabaena. It has previously been shown that the nitrite reductase protein NirA requires NirB, a protein likely involved in protein-protein interactions, to attain maximum activity. Bacterial two-hybrid analysis confirmed possible NirA-NirB and NarB-NarM interactions, suggesting that the development of both nitrite reductase and nitrate reductase activities in cyanobacteria involves physical interaction of the corresponding enzymes with their cognate partners, NirB and NarM, respectively. IMPORTANCE Nitrate is an important source of nitrogen for many microorganisms that is utilized through the nitrate assimilation system, which includes nitrate/nitrite membrane transporters and the nitrate and nitrite reductases. Many cyanobacteria assimilate nitrate, but regulation of the nitrate assimilation system varies in different cyanobacterial groups. In the N2-fixing, heterocyst-forming cyanobacteria, the nirA operon, which includes the structural genes for the nitrate assimilation system, is expressed in the presence of nitrate or nitrite if ammonium is not available to the cells. Here we studied the genes required for production of an active nitrate reductase, providing information on the nitrate-dependent induction of the operon, and found evidence for possible protein-protein interactions in the maturation of nitrate reductase and nitrite reductase.
Prevalence and factors associated with different pathogens of acute diarrhea in adults in Beijing, China.

INTRODUCTION Only a small proportion of patients with diarrhea are diagnosed with laboratory tests in China, and most are diagnosed based on clinical symptoms. Therefore, understanding the prevalence of different diarrheal pathogens and their specific symptoms is important. METHODOLOGY Data from a prospective study in Beijing of acute diarrhea and the related pathogens were used to study the association between different pathogen groups and the infected patients' characteristics. A total of 355 patients with acute diarrhea, clinically diagnosed with infectious or noninfectious diarrhea by general practitioners (GPs), were recruited from three districts. RESULTS Different species of diarrheal pathogens were detected in 133 (37.5%) patients. The most prevalent pathogen was calicivirus (42.9%), followed by rotavirus (30.1%), Vibrio parahaemolyticus (13.5%), and Salmonella spp. (10.5%). The detection rates in patients diagnosed with infectious or noninfectious diarrhea by GPs did not differ significantly (c2 = 0.026, p = 0.873). Abdominal pain correlated negatively with viral pathogens, whereas nausea, living in the suburbs, and winter infection correlated positively with viral infection. Abdominal pain and leukocytosis were positively associated with bacterial infections, whereas winter infection correlated negatively with them. CONCLUSION In this study, we found that the detection rates in patients diagnosed with infectious or noninfectious diarrhea by GPs was the same. We also revealed the improper prescription of antibiotics by GPs based simply on clinical diagnoses. A further analysis of diagnostic accuracy and methods is required to assist GPs in improving their diagnoses when insufficient laboratory tests are available and budgets are limited.
Single-Prick Infiltration Anesthesia for External Dacryocystorhinostomy

Purpose: To determine the effectiveness, complications and patient acceptance of single-prick local anesthesia for external dacryocystorhinostomy (DCR). Methods: Data were prospectively collected from January 2004 to March 2006 on 463 patients undergoing external DCR operated by a single surgeon. All surgeries were performed under single-prick local infiltration anesthesia. Replies to the Verbal Rating Scale (VRS) were recorded to measure pain intraoperatively at various steps of the surgery. Patients were specifically asked about discomfort during the surgery and whether they would undergo surgery under the same anesthesia if needed for the other eye. Results: The mean operative duration was 15.50 minutes (range 14–18 minutes). There were 298 females and 165 males. The mean age was 46.5 years (range 17–81 years). The patients reported being comfortable during and immediately after surgery. The VRS was 3–4 (mild pain) for the degree of pain during bone removal and flaps formation. The VRS was 0–2 (no pain) during skin incision and wound closure. None of the patients required additional anesthesia during surgery. None of the patients complained of nausea or vomiting intraoperatively or in the immediate postoperative period. The majority of the patients preferred the same anesthetic technique for surgery in the other eye if required. Conclusions: Single-prick local infiltration anesthesia for external DCR is safe, effective and has good patient acceptance.
Analysis of the Functions of Herpes Simplex Virus Type 1 Regulatory Protein ICP0 That Are Critical for Lytic Infection and Derepression of Quiescent Viral Genomes

ABSTRACT Herpes simplex virus type 1 (HSV-1) immediate-early regulatory protein ICP0 is important for stimulating the initiation of the lytic cycle and efficient reactivation of latent or quiescent infection. Extensive investigation has suggested several potential functions for ICP0, including interference in the interferon response, disruption of functions connected with PML nuclear bodies (ND10), and inhibition of cellular histone deacetylase (HDAC) activity through an interaction with the HDAC-1 binding partner CoREST. Analysis of the significance of these potential functions and whether they are direct or indirect effects of ICP0 is complicated because HSV-1 mutants expressing mutant forms of ICP0 infect cells with widely differing efficiencies. On the other hand, transfection approaches for ICP0 expression do not allow studies of whole cell populations because of their limited efficiency. To overcome these problems, we have established a cell line in which ICP0 expression can be induced at levels pertaining during the early stages of HSV-1 infection in virtually all cells in the culture. Such cells enable 100% complementation of ICP0-null mutant HSV-1. Using cells expressing the wild type and a variety of mutant forms of ICP0, we have used this system to analyze the role of defined domains of the protein in stimulating lytic infection and derepression from quiescence. Activity in these core functions correlated well the ability of ICP0 to disrupt ND10 and inhibit the recruitment of ND10 proteins to sites closely associated with viral genomes at the onset of infection, whereas the CoREST binding region was neither sufficient nor necessary for ICP0 function in lytic and reactivating infections.
Beneficial effects of ‘lamivudine pulse’ therapy in HBeAg‐positive patients with normal ALT *

Summary. Currently no therapy is given to patients with chronic hepatitis B virus (HBV) infection who are HBeAg positive with normal alanine aminotransferase (ALT) levels. Steroid priming has been shown to enhance T‐helper‐1 (Th‐1) cell response. Lamivudine may restore immunologic competence against HBV by causing a sudden decline in the level of the virus. We examined the efficacy of lamivudine pulse therapy on the seroconversion from HBeAg to anti‐HBe. This was a prospective single‐blinded trial including 27 patients with chronic hepatitis B, HBeAg positive with ALT ≤1.5 times upper limit of normal (ULN). Lamivudine was administered initially for 4 weeks, then stopped for 2 weeks and later restarted and continued till 3 months after seroconversion or completion of 2 years of therapy. Twenty‐six patients completed the study. Lamivudine withdrawal led to a rise in ALT levels above the ULN in 11 (42.3%) patients at 6 weeks; seven of them (63.6%) lost HBeAg compared with only two of the 15 patients (13.3%), in whom ALT levels did not rise (P = 0.011). As one patient showed a relapse, a total of eight (31%) patients responded to lamivudine pulse therapy over a mean period of 17.3 ± 4.5 months. Responders had a higher serum albumin (P < 0.05), a lower fibrosis score (P < 0.05), and a relatively high baseline serum ALT levels (P = 0.024) than the nonresponders. YMDD mutations developed in three patients and none responded. No patient developed hepatic decompensation. Hence lamivudine pulse therapy has potential in converting HBeAg‐positive, ‘not‐treat‐worthy’ (ALT < 1.5 ULN) patients to treat‐worthy (ALT > 1.5 ULN) in 42%, with sustained HBeAg and HBV DNA loss in 31% patients. The effects are possibly because of a combination of antiviral and immunomodulating activities of lamivudine.
Establishing the Embryonic Axes: Prime Time for Teratogenic Insults

A long standing axiom in the field of teratology states that the teratogenic period, when most birth defects are produced, occurs during the third to eighth weeks of development post-fertilization. Any insults prior to this time are thought to result in a slowing of embryonic growth from which the conceptus recovers or death of the embryo followed by spontaneous abortion. However, new insights into embryonic development during the first two weeks, including formation of the anterior-posterior, dorsal-ventral, and left-right axes, suggests that signaling pathways regulating these processes are prime targets for genetic and toxic insults. Establishment of the left-right (laterality) axis is particularly sensitive to disruption at very early stages of development and these perturbations result in a wide variety of congenital malformations, especially heart defects. Thus, the time for teratogenic insults resulting in birth defects should be reset to include the first two weeks of development.
Access to bank finance for UK SMEs in the wake of the recent financial crisis

Purpose The purpose of this paper is to investigate how entrepreneurs demand for external finance changed as the economy continued to be mired in its third and fourth years of the global financial crisis (GFC) and whether or not external finance has become more difficult to access as the recession progressed. Design/methodology/approach Using a large-scale survey data on over 30,000 UK small- and medium-sized enterprises between July 2011 and March 2013, the authors estimate a series of conditional probit models to empirically test the determinants of the supply of, and demand for external finance. Findings Older firms and those with a higher risk rating, and a record of financial delinquency, were more likely to have a demand for external finance. The opposite was true for women-led businesses and firms with positive profits. In general finance was more readily available to older firms post-GFC, but banks were very unwilling to advance money to firms with a high-risk rating or a record of any financial delinquency. It is estimated that a maximum of 42,000 smaller firms were denied credit, which was significantly lower than the peak of 119,000 during the financial crisis. Originality/value This paper provides timely evidence that adds to the general understanding of what really happens in the market for small business financing three to five years into an economic downturn and in the early post-GFC period, from both a demand and supply perspective. This will enable the authors to consider what the potential impacts of credit rationing on the small business sector are and also identify areas where government action might be appropriate.