Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel in vivo post‐translational modification of p53 by PARP‐1 in MPTP‐induced parkinsonism

Sporadic Parkinson's disease (PD) affects primarily dopaminergic neurons of the substantia nigra pars compacta. There is evidence of necrotic and apoptotic neuronal death in PD, but the mechanisms behind selected dopaminergic neuronal death remain unknown. The tumor suppressor protein p53 functions to selectively destroy stressed or abnormal cells during life and development by means of necrosis and apoptosis. Activation of p53 leads to death in a variety of cells including neurons. p53 is a target of the nuclear enzyme Poly(ADP‐ribose)polymerase (PARP), and PARP is activated following DNA damage that occurs following 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced neurotoxicity. MPTP is the favored in vivo model of PD, and reproduces the pathophysiology, anatomy and biochemistry of PD. p53 protein normally exhibits a fleeting half‐life, and regulation of p53 stability and activation is achieved mainly by post‐translational modification. We find that p53 is heavily poly(ADP‐ribosyl)ated by PARP‐1 following MPTP intoxication. This post‐translational modification serves to stabilize p53 and alters its transactivation of downstream genes. These influences of PARP‐1 on p53 may underlie the mechanisms of MPTP‐induced parkinsonism and other models of neuronal death.
Protective role of COMP‐Ang1 in ischemic rat brain

In cerebral ischemia, the induction of angiogenesis may represent a natural defense mechanism that enables the hypoxic brain to avoid progression into infarction. Angiopoietin‐1 (Ang1) is known to produce non‐leaky and stable blood vessel formation mainly by the Tie2 receptor. Therefore, we envisioned that the application of cartilage oligomeric matrix protein‐Ang1 (COMP‐Ang1), a soluble, stable, and potent form of Ang1, would promote angiogenesis and provide a protective effect following unilateral middle cerebral artery occlusion (MCAO) in rats. To this end, we employed a 2‐hour‐MCAO model, and treated rats with adenovirus encoding COMP‐Ang1 (Ade‐COMP‐Ang1) or control virus encoding β‐gal (Ade‐β‐gal). Time course magnetic resonance images (MRIs) revealed significantly reduced infarct volume in the rats treated with Ade‐COMP‐Ang1 with an improvement of post‐ischemic neurological deficits compared with rats treated with Ade‐β‐gal. Moreover, compared to the rats treated with Ade‐β‐gal, the rats treated with Ade‐COMP‐Ang1 showed an increase in blood vessels, especially in the border zone adjacent to the infarction, increased number of endogenous neuronal progenitor cells in the ischemic brain, and decreased number of TUNEL‐positive cells. Taken together, COMP‐Ang1 reduced infarct volume and consequently attenuated post‐ischemic neurological deficits through enhanced angiogenesis and increased viable cell mass of neuronal cells. © 2009 Wiley‐Liss, Inc.
Anxiolytic activity of SC-48274 compared with those of buspirone and diazepam in experimental anxiety models.

The present study was performed to assess the anxiolytic activity of the novel anxiolytic SC-48274 in comparison with those of buspirone and diazepam. Drugs were administered p.o. The experimental anxiety models included gastric lesions of mice induced by socio-psychological stress in the communication box (CB) and the passive avoidance paradigm in rats. In the CB experiments, non-foot-shocked mice (responder) exposed to the emotional responses of foot-shocked mice (sender), 3 hr per day for 3 days, developed gastric lesions. Single treatments of diazepam (1, 2, 5 mg/kg) and SC-48274 (25, 50 mg/kg) prevented gastric lesion formation, but buspirone at 2.5-10 mg/kg did not. A 3-day treatment with SC-48274 at doses over 5 mg/kg prevented gastric lesions; and a 3-day treatment with buspirone at 2, 5 and 10 mg/kg prevented the lesions with a U-shaped dose-response. Diazepam also prevented gastric lesion formation at the doses of 1 and 2 mg/kg. In the passive avoidance response study, rats which had a single acquisition trial for 2 days were used. The step-down latency for rats to enter from the illuminated compartment to the dark one was recorded. Single treatments of SC-48274 (25 mg/kg), diazepam (5, 10 mg/kg) or buspirone (25 mg/kg) shortened the delayed latency. These results suggest that SC-48274 has anxiolytic activity of the same potency as buspirone and repeated-dose administration is needed to induce anxiolytic activity.
Paid vacation use: The role of works councils

The article investigates the relationship between codetermination at the plant level and paid vacation in Germany. From a legal perspective, works councils have no impact on vacation entitlements, but they can affect their use. Employing data from the German Socio-Economic Panel (SOEP), the study finds that male employees who work in an establishment, in which a works council exists, take almost two additional days of paid vacation annually, relative to employees in an establishment without such institution. The effect for females is much smaller, if discernible at all. The data suggest that this gender gap might be due to the fact that women exploit vacation entitlements more comprehensively than men already in the absence of a works council.
Importance of the detection of amoebic antigens in stool samples for the diagnosis of Entamoeba histolytica infection, among children in southern Turkey

Abstract Entamoeba histolytica is the predominant causative agent of human amoebiasis, a significant and common diarrhoeal disease among children of developing countries. Diagnosis of this illness by the microscopical detection of the parasites in stool samples is insensitive and often incapable of differentiating the pathogenic Entamoeba histolytica from the commensal parasite E. dispar. In this study, the results of testing stool samples in an ELISA, based on a monoclonal antibody, that detects E. histolytica-specific galactose adhesin were compared against the results of the microscopical examination of the same samples. The samples investigated came from 131 children (aged <15 years) with diarrhoea, who lived in the provinces of Adana and Mersin, in southern Turkey. Overall 22 cases of E. histolytica infection, including eight that appeared negative by microscopy, were detected using the ELISA. The 16 patients considered positive for E. histolytica/E. dispar by microscopy included two who were ELISA-negative. With the ELISA results used as the 'gold standard', and assuming that all the E. histolytica/E. dispar cysts seen by microscopy were E. histolytica, microscopy had a specificity of 98.2%, a positive predictive value of 87.5% and a negative predictive value of 93.1% but a sensitivity of only 63.6%. Compared with microscopy, culture and PCR-based assays, the antigen-detection ELISA appears to be easier, faster and probably more cost-effective, with high sensitivity, specificity and predictive values.
Selection for c-myc Integration Sites in Polyclonal T-Cell Lymphomas

ABSTRACT Type B leukemogenic virus (TBLV) is highly related to mouse mammary tumor virus but induces rapidly appearing T-cell lymphomas in mice. Unlike other T-cell tumors induced by retroviruses, only 5 to 10% of TBLV-induced lymphomas have detectable viral integrations near c-myc by Southern blotting, whereas Northern blotting has shown that most tumors have two- to sixfold overexpression of c-myc RNA. In this report, PCR was used to demonstrate that at least 30% of these lymphomas have TBLV insertions near c-myc. Some tumors contained multiple TBLV proviruses in different locations and orientations, suggesting that the tumors are polyclonal. The integrated proviruses near c-myc had different numbers (two to four) of long terminal repeat (LTR) enhancer repeats, although LTRs with three-repeat enhancers dominated the proviral population. Passage of polyclonal tumors in immunocompetent mice and semiquantitative PCR revealed that only cells with particular integrations were selected for growth. In three of six tumors tested, proviruses containing four-repeat enhancers near c-myc were selected during tumor passage. Since tumor cell selection may be accomplished by overexpression of c-myc RNA due to proximity to the unique TBLV LTR enhancer, we inserted LTRs at various locations within a plasmid containing the entire c-myc locus and cellular flanking sequences. To quantitatively measure effects on transcription, the Renilla luciferase gene was substituted for most of c-myc exon 2, and transient transfections were performed with c-myc reporter constructs in two different T-cell lines. As expected, insertion of a TBLV LTR with three-repeat enhancers in either orientation, 5" and 3", of the myc gene elevated reporter activity from 2- to 160-fold, consistent with enhancer function, but four-repeat LTRs had lower levels of expression compared to three-repeat LTRs. Surprisingly, LTR insertions that gave maximal c-myc expression in transient-transfection assays declined in tumor cells selected for growth in vivo. Selection for clonal growth may occur in tumor cells that have modest c-myc overexpression after proviral insertion to prevent apoptosis.
The results of the second World Photovoltaic Scale recalibration

The World Photovoltaic Scale (WPVS) is used as a worldwide reference value for terrestrial PV performance measurements of I/sub STC/, the short-circuit current under standard test conditions. The WPVS has already been established in 1997 based on an international comparison where a set of 20 transfer/travelling standards were circulated between 11 national laboratories. After the first recalibration carried out at NREL in 1999, the PTB acted as pilot laboratory for the second recalibration, i.e. the 2003/04 intercomparison. It was performed as an international star-like comparison with 43 reference solar cells as reference standards, where 25 reference solar cells were made in accordance with the WPVS reference cell package design. Nine institutes have participated: AIST (Japan), BGNSEC (Israel), CIEMAT (Spain), ESTI (EU), Fraunhofer ISE (Germany), NREL (USA), PTB (Germany), Sandia (USA), TIPS (China). The measurements of the pilot laboratory were carried out between August 2003 and January 2004. Summarizing the main result of the comparison, the deviations of the calibration values obtained by the pilot laboratory and by the participants are, in general, within /spl plusmn/2%. In addition to the results of the comparison, typical stability and linearity test results of some reference cells as well as reproducibility of the DSR calibration facility of the pilot laboratory are described and discussed. Finally, the recommendations of a working group concerning the future development of the WPVS are presented.
Dissimilation of Carbon Monoxide to Acetic Acid by Glucose-Limited Cultures of Clostridium thermoaceticum

Clostridium thermoaceticum was cultivated in glucose-limited media, and the dissimilation of CO to acetic acid was evaluated. We found that cultures catalyzed the rapid dissimilation of CO to acetic acid and CO2, with the stoichiometry obtained for conversion approximating that predicted from the following reaction: 4CO + 2H2O → CH3CO2H + 2CO2. Growing cultures formed approximately 50 mmol (3 g) of CO-derived acetic acid per liter of culture, with the rate of maximal consumption approximating 9.1 mmol of CO consumed/h per liter of culture. In contrast, resting cells were found not to dissimilate CO to acetic acid. 14CO was incorporated, with equal distribution between the carboxyl and methyl carbons of acetic acid when the initial cultivation gas phase was 100% CO, whereas 14CO2 preferentially entered the carboxyl carbon when the initial gas phase was 100% CO2. Significantly, in the presence of saturating levels of CO, 14CO2 preferentially entered the methyl carbon, whereas saturating levels of CO2 yielded 14CO-derived labeling predominantly in the carboxyl carbon. These findings are discussed in relation to the path of carbon flow to acetic acid.
The intestinal microbiota in inflammatory bowel diseases: time to connect with the host

Purpose of review The aim of this review is to report recent findings regarding the role of the gut microbiota in inflammatory bowel disease pathogenesis. Recent findings After a description of the current knowledge on inflammatory bowel diseases-associated dysbiosis, we will focus on the recent functional studies that analyzed the cross relationship between the gut microbiota and the host. Summary Recently published studies have provided an insight into the altered dialog between the intestinal microbiota and the host leading to gut inflammation. Further investigation will allow identifying new therapeutic targets either in the microbiota or the host.
Entrepreneurs' Demographic Characteristics and the Social Responsibility Information Disclosure

The prior researches just concentrate on the relationship between social responsibility information disclosure and the corporate characteristics and corporate governance,are limited to the sample of annual reports.This paper examines whether the characteristics of entrepreneurs' demographic characteristics are correlated to the social responsibility information disclosure.On the basis of the survey and questionnaire of the specialists and reports users,this paper establishes some scientific standards to evaluate the level of the social responsibilities information disclosure.Meanwhile,this paper conducts an empirical analysis which comprises a sample of 1207 social responsibility reports taken from 2008 to 2010 in China's listed companies.The empirical evidence indicates that the correlation between entrepreneurs' educational,age,social reputation and the social responsibility information level is significantly positive.Moreover,this paper finds that there are differences between the non-state owned companies and the state-owned companies by analyzing property rights of characteristics of the listed companies.The significance of this paper is that it provides a new perspective that the entrepreneurs' demographic characteristics must be taken into account,when the corporate social responsibility information disclosure is studied.Meanwhile,this paper helps us better understand the motives of the corporate social responsibility information disclosure,and is of great significance in the selection of entrepreneurs in state-owned companies.
Genetic factors underlying the risk of bortezomib induced peripheral neuropathy in multiple myeloma patients

Bortezomib induced peripheral neuropathy is a dose-limiting side effect and a major concern in the treatment of multiple myeloma. To identify genetic risk factors associated with the development of this side effect in bortezomib treated multiple myeloma patients, a pharmacogenetic association study was performed using a discovery set (IFM 2005-01; n=238) and a validation set (HOVON65/GMMG-HD4 and a Czech dataset; n=231). After multiplicity correction, none of the 2,149 single nucleotide polymorphisms tested revealed any significant association with bortezomib induced peripheral neuropathy. However, 56 single nucleotide polymorphisms demonstrated an association with bortezomib induced peripheral neuropathy with pointwise, uncorrected significance. Pathway analysis of these polymorphisms demonstrated involvement of neurological disease (FDR <20%). Also a clear enrichment of major bortezomib metabolizing genes was found. Univariate evaluation of these 56 polymorphisms in the validation set demonstrated one single nucleotide polymorphism with pointwise significance: rs619824 in CYP17A1.
The Effects of Sucrose on Everyday Eating in Normal Weight Men and Women

Energy intake was estimated from the food diaries of 52 overnight-fasted adult volunteers after ingestion of 110 ml of a solution of either 40 g of sucrose or 4.34 g of saccharin administered in blind conditions. Men consumed more calories and carbohydrates than women. Women's eating was unaffected by the preload. The sucrose preload led to 60% of male subjects choosing to consume a calorific beverage soon afterwards; they then delayed eating compared to men who received a saccharin preload. Men who had received sucrose, but consumed no beverage, ate as early as the saccharin preload group. It is concluded that under fasted, blind administration followed by everyday eating, sucrose does not increase hunger, but eating behaviour after a preload varies with eating habits.
Low NaCl intake elevates renal medullary endothelin‐1 and endothelin A (ETA) receptor mRNA but not the sensitivity of renal Na+ excretion to ETA receptor blockade in rats

Aims: This study was performed to investigate the effects of NaCl intake on renal mRNA expression of pre‐pro‐endothelin‐1 (ET‐1), endothelin A (ETA) and endothelin B (ETB) receptors as well as on renal ET‐1 content in rats. We further tested for NaCl intake‐dependent differences in the contribution of the ET system to renal sodium handling.
TMT Departures and Post‐IPO Outside Director Additions: Implications for Young IPO Firms’ Survival and Performance

We draw on resource‐based logic to argue that relatively stable TMTs and boards are beneficial for young IPO firms because of the need to maintain and develop valuable firm‐specific capabilities and psychological attachment of pre‐IPO TMTs. Using panel data from 272 young IPO firms, we find that pre‐IPO TMT member exits negatively affect young IPO firms’ survival and performance. This negative effect is greater when more post‐IPO outside directors are added. We also find that the above interaction is positively and negatively associated with survival and performance when TMT ownership declines substantially and when firms have a founder CEO, respectively.
Regional imbalances and impact of soil health card on fertilizer consumption in Gujarat

The present study was undertaken with a view to assess the growth in fertilizer consumption and fertilizer use pattern, to examine the gap between actual use and recommended dose of fertilizer, to study the determinants of fertilizer use, to estimate the fertilizer use efficiency and to study the impact of Soil Health Card on consumption of fertilizer in South Gujarat region. Multistage random sampling technique was used for sample selection. Total sample size comprised of 224 farmers with 50-50 per cent from with and without Soil Health Cards. The primary data were collected for the agricultural year 2010-11 by survey method. The results of the study revealed that among all the crops in South Gujarat region, the highest area was allocated to sugarcane crop, followed by kharif paddy and summer paddy. Among the regions, Middle Gujarat stood at top in consumption of N during all periods and Kutchh stood at the bottom. During the Period–I, IV and VI, the consumption of N fertilizer significantly increased in all the regions of Gujarat state. During Period–II and Period-III, the consumption of N increased significantly in all regions except Saurashtra region. Gujarat as a
Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial–mesenchymal transition

Significance Some cancers, termed carcinosarcomas (CSs), have mixed cell types, with either epithelial or mesenchymal features. Sequencing the genomes of uterine and ovarian CSs demonstrated that these different cell types derive from a common precursor cell that has many mutations typical of epithelial cancers. In addition, we find that these tumors have a significant burden of point mutations and amplification of histone genes, suggesting a potential role of these mutations in sarcomatous transformation. Consistent with this finding, expression of specific histone gene mutations in uterine carcinoma cells changed gene expression toward a mesenchymal state. These findings have potential implications for the treatment of these cancers. Carcinosarcomas (CSs) of the uterus and ovary are highly aggressive neoplasms containing both carcinomatous and sarcomatous elements. We analyzed the mutational landscape of 68 uterine and ovarian CSs by whole-exome sequencing. We also performed multiregion whole-exome sequencing comprising two carcinoma and sarcoma samples from six tumors to resolve their evolutionary histories. The results demonstrated that carcinomatous and sarcomatous elements derive from a common precursor having mutations typical of carcinomas. In addition to mutations in cancer genes previously identified in uterine and ovarian carcinomas such as TP53, PIK3CA, PPP2R1A, KRAS, PTEN, CHD4, and BCOR, we found an excess of mutations in genes encoding histone H2A and H2B, as well as significant amplification of the segment of chromosome 6p harboring the histone gene cluster containing these genes. We also found frequent deletions of the genes TP53 and MBD3 (a member with CHD4 of the nucleosome remodeling deacetylase complex) and frequent amplification of chromosome segments containing the genes PIK3CA, TERT, and MYC. Stable transgenic expression of H2A and H2B in a uterine serous carcinoma cell line demonstrated that mutant, but not wild-type, histones increased expression of markers of epithelial–mesenchymal transition (EMT) as well as tumor migratory and invasive properties, suggesting a role in sarcomatous transformation. Comparison of the phylogenetic relationships of carcinomatous and sarcomatous elements of the same tumors demonstrated separate lineages leading to these two components. These findings define the genetic landscape of CSs and suggest therapeutic targets for these highly aggressive neoplasms.
Intrauterine rescue transfusion in monochorionic multiple pregnancies with recent single intrauterine death

To assess the role of fetal blood sampling and intrauterine transfusion in monochorionic (MC) multiple pregnancy complicated by single intrauterine death (IUD), we reviewed ten cases over a 4‐year period in a tertiary referral centre which underwent fetal blood sampling within 24 h of death of its MC co‐twin. Intrauterine rescue transfusion was performed in all seven anaemic fetuses (hematocrit; Hct<30%) to raise the fetal Hct to ≥40%. The rationale was to prevent death and/or brain injury. Two fetuses, which were severely acidaemic at blood sampling, died in utero within 24 h of the procedure. In two cases, the surviving twins manifested abnormal sonographic findings of the fetal brain 2–5 weeks later and underwent late termination. In two cases, the pregnancies continued uneventfully until delivery at 35 and 40 weeks' gestation with good neonatal outcome. In one case the co‐twin delivered 1 week later at 29 weeks but died within 12 h. Fetuses without anaemia were not transfused and had normal clinical outcomes. We suggest that intrauterine rescue transfusion before the development of severe acidaemia in anaemic surviving MC co‐twins may prevent fetal death, but does not necessarily prevent brain injury. Until its role becomes clearer, we recommend that its use be restricted to situations in which the parents and the local jurisdiction allow late termination as an option if brain injury subsequently manifests on ultrasound. Copyright © 2001 John Wiley & Sons, Ltd.