Miracle-dz/UniFAR-FTUs huggingface dataset:
The Influence of Platelet Glycoprotein Polymorphisms on Receptor Function and Risk for Thrombosis

With regard to hemostasis and thrombosis, collagens are among the most important physiologic components of the extracellular matrix in their role as platelet activators. Differences in the rate of platelet activation markedly influence normal hemostasis and the pathological outcome of thrombosis. Thus, collagen receptors, such as the integrin alpha2beta1 and indirectly, GPIb alpha, represent a relatively unexploited target of pharmacological control and are only recently becoming appreciated as potential factors in the generic risk for thrombosis. In general, the importance platelet glycoprotein polymorphisms as genetic risk factors for arterial thrombosis is a new area of human genomics that needs to be carefully addressed. Discrepancies in the degree to which they are reported to contribute to risk for clinical thrombosis will only be resolved once there is a universal standard for clinical study design. Most of the clinical studies differ by patient population size, ethnicity, bias in the selection of patients and controls, plurality in clinical endpoints and variation of environmental factors. Despite these differences, there is substantial evidence that the integrin beta3 PlA2 haplotype, the GPIb alpha Met145 haplotype, the GPIb alpha -5C haplotype and the integrin alpha2 haplotype 1 (807T) each contribute to the risk for and morbidity of thrombotic disease. There may remain dispute as to the extent of their contribution. However, well-designed, large, prospective, genetic and epidemiologic studies are needed to clarify the role of these and other platelet receptor polymorphisms. Most importantly, the cumulative effects of multiple platelet and plasma glycoproteins SNPs to thrombotic risk must be evaluated concurrently. Additional in vitro studies of the functional relevance underlying these polymorphisms are needed to provide a sound biological explanation for the results of clinical correlations. The opportunity now exists to make significant inroads into the development of strategies for the prevention of thrombotic disease.
Role of lupeol and its ester on cyclophosphamide‐induced hyperlipidaemic cardiomyopathy in rats

Cyclophosphamide, an alkylating agent widely used in cancer chemotherapy, causes fatal cardiotoxicity. In this study, lupeol, a pentacyclic triterpene isolated from Crataeva nurvala stem bark, and its ester, lupeol linoleate, were investigated for their possible hypocholesterolaemic effects against cyclophosphamide‐induced lipidaemic instabilities. Male albino Wistar rats were categorized into 6 groups. Group I served as control. Rats in groups II, V and VI were injected intraperitoneally with a single dose of cyclophosphamide (200 mg kg−1) dissolved in saline. Cyclophosphamide‐treated groups V and VI respectively received lupeol and lupeol linoleate (50 mg kg−1), dissolved in olive oil, for 10 days by oral gavage. Groups III and IV served as drug controls and were administered lupeol and lupeol linoleate, respectively. Cyclophosphamide administration induced abnormal changes in serum lipoproteins and lipid fractions in both serum and cardiac tissue. The activity of lipid metabolizing enzymes was distorted significantly in the cyclophosphamide‐treated rats. The cyclophosphamide‐treated rats also showed extensive intermuscular haemorrhage in histology. Lupeol and its ester reversed the above alterations induced by cyclophosphamide. This study encapsulates the early lipaemic abnormalities in the heart tissue of cyclophosphamide‐treated rats. Treatment with lupeol linoleate was more effective than lupeol in rendering protection to the cardiac tissue challenged by cyclophosphamide.
Involvement of U1 Small Nuclear Ribonucleoproteins (snRNP) in 5′ Splice Site-U1 snRNP Interaction*

U1 small nuclear ribonucleoprotein (snRNP) is an important ribonucleoprotein involved early in the spliceosome formation to commit pre-mRNAs to the splicing pathway. We have determined the association and dissociation kinetics of the 5′ splice site-U1 snRNP interaction using purified U1 snRNP and a short RNA oligonucleotide comprising the 5′ splice site (5′-SS) consensus sequence of pre-mRNAs (5′-SS RNA oligo). The association is rapid, does not require ATP, and is almost irreversible. Surprisingly, oligonucleotide-directed cleavage of the U1 small nuclear RNA (snRNA) 5′ end sequence with RNase H has no significant effect on the rate of association of the 5′-SS RNA oligo, but it does lead to rapid dissociation. This provides evidence that U1-specific snRNP proteins are critical for the 5′ splice site recognition while base pairing ensures the stability of the interaction. The recognition of the 5′ splice site by U1 snRNP does not result from the individual action of one or more proteins but rather from their organization around U1 snRNA. A consequence of this organization is that the U1-C protein makes direct contacts with the site, as it becomes cross-linked to the RNA oligo upon exposition of the reactions to shortwave UV light.
PENGARUH RISIKO LIKUIDITAS DAN LEVERAGE TERHADAP KINERJA BANK YANG TERDAFTAR DI BURSA EFEK INDONESIA PERIODE 2010--2015

This empirical study aims for examining the influence of liquidity risk on bank performance from the period 2010 to 2015 listed on Indonesia Stock Exchange. The measurement of liquidity risk will involve deposits or third-party fund, cash, and liquidity gap whereas the leverage will involve total debts to total assets as the independent variables. Meanwhile, the dependent variables of this study involve ROA and Tobin’s Q. This study was conducted under the purposive sampling method which involved 22 banks as samples. This study also used a panel data regression method and three testing models, including Common Effect Model, Fixed Effect Model, and Random Effect Model. The findings suggest a positive and significant influence of the third-party fund on ROA and Tobin’s Q. In contrast, the liquidity gap has a negative and significant influence on ROA and Tobin’s Q. Besides, the findings also suggest a positive and significant influence of cash on ROA and negatively significant on Tobin’s Q. The leverage has negative and significant influence on ROA and positively significant on Tobin’s Q.
Influence of perfusate on liver viability during hypothermic machine perfusion.

AIM To optimize the perfusates used for hypothermic machine perfusion (HMP). METHODS Sprague-Dawley rats were assigned randomly to three groups (n = 12 per group) that received either saline, University of Wisconsin cold-storage solution (UW) or histidine-tryptophan-ketoglutarate solution (HTK) as the perfusate. Each group was divided into two subgroups: static cold storage (SCS) and HMP (n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate (0-4 °C) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight (D/W) ratio, and malondialdehyde (MDA) and adenosine-triphosphate (ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups. RESULTS Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period (SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level (saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline (vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently (vs saline, 0.68 ± 0.02 vs 0.79 ± 0.05, P = 0.013), while HTK maintained ATP levels best (vs saline, 622.60 ± 29.11 vs 327.43 ± 44.66, P < 0.001; vs UW, 622.60 ± 29.11 vs 301.80 ± 37.68, P < 0.001). CONCLUSION HMP is superior to SCS in maintaining both architecture and function of liver grafts. Further, HTK was found to be the optimal perfusate for HMP.
An observational study of 256 cases of vascular trauma in the north western province of Pakistan.

During the past 10 years Peshawar has dealt with increasing casualties with penetrating trauma inflicted by a wide variety of missiles. The aim of this study was to assess whether delay in arrival and mode of presentation affects the outcome of patients with penetrating vascular trauma. Prospective data were collected on 256 vascular injuries in 248 patients (median age, 29 years; range, 7-60 years) between January 1995 and June 1998. Early presentation (group A, 55 cases, < 12 h) was compared with late presentation (group B, 201 cases, > 12 h). The majority of injuries (93%) were caused by fire-arms. Arterial injuries accounted for 71% of the total, venous injuries accounted for 10% and 19% were mixed. The site of injury was the lower limb (61%), upper limb (32%), abdominal cavity (5%) and neck (2%). Patients presented with absent pulses (56%), haemorrhage (46%), false aneurysms (8%), A-V fistula (5%) and 11% presented with more than one sign. There were significantly more lower limb amputations in group A than group B (23% versus 5%; P < 0.05), with fractures having a positive association with lower limb amputations (odds ratio, 0.32; 95% CI, 0.13-0.94; P < 0.05). Group A had a higher mortality than group B (18% versus 7%; P < 0.05). This study shows that patients with vascular trauma can be managed successfully with clinical assessment alone. Patients with fractures were more likely to suffer eventually from lower limb loss. Due to self-selection, arrival at the hospital less than 12 h after sustaining vascular injury was associated with a higher mortality than those presenting after 12 h.
Severe pulmonary toxicity in patients with advanced-stage Hodgkin's disease treated with a modified bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine (BEACOPP) regimen is probably related to the combination of gemcitabine and bleomycin: a report of the 

PURPOSE To investigate a new effective, nonleukemogenic polychemotherapy regimen, BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, gemcitabine) in a phase I/II dose-escalation study in patients with advanced-stage Hodgkin' s disease (HD). PATIENTS AND METHODS Patients in clinical stages IIB with risk factors III and IV were enrolled in this nonrandomized, multicenter trial aimed at defining the maximum-tolerated dose of gemcitabine within a modified escalated BEACOPP regimen. Gemcitabine was given at a starting dose of 800 mg/m(2) on days 1 and 4 of each cycle. RESULTS Twenty-seven patients (eight female, 19 male) were enrolled with a median age of 33 years (range, 19 to 65 years). Due to a higher than expected hematotoxicity, the day-4 application of gemcitabine was omitted after 14 patients were included and 59 cycles were given. A total of eight patients developed lung toxicity, mainly pneumonitis (six of eight), which led to the termination of the study. With a median follow-up of 27 months, 25 patients are in continuing complete remission. CONCLUSION The substitution of etoposide by gemcitabine in the escalated BEACOPP schema is not feasible and leads to severe pulmonary toxicity. This toxicity is probably related to the concomittant application of gemcitabine and bleomycin.
Structural Organization of the Microsomal Glutathione S-Transferase Gene (MGST1) on Chromosome 12p13.1–13.2

The structure and regulation of the microsomal glutathione S-transferase gene (MGST1) are considerably more complex than originally perceived to be. TheMGST1 gene has two alternative first exons and is located in the 12p13.1–13.2 region. Two other potential first exons were determined to be nonfunctional. The region between the functional first exons cannot direct transcription. Thus, one common promoter element directing transcription exists, and RNA splicing occurs such that only one of the first exons (containing only untranslated mRNA) is incorporated into each mRNA species with common downstream exons.MGST1 expression and regulation are therefore similar to those of other hepatic xenobiotic handling enzymes, which also produce mRNA species differing only in the 5′-untranslated regions to yield identical proteins. MGST1 was previously considered a “housekeeping” gene, as non-oxidant inducers had little effect on activity. However, the promoter region immediately upstream of the dominant first exon transcriptionally responds to oxidative stress. In this respect, MGST1 is similar to glutathione peroxidases that also transcriptionally respond to oxidative stress. The discovery that MGST1 utilizes alternative first exon splicing eliminates a problem with the first description of MGST1cDNA in that it appeared that MGST1 expression was in violation of the ribosomal scanning model. The identification that the first exon originally noted is in fact a minor alternative first exon far downstream of the primary first exon eliminates this conundrum.
ATP Inhibits the Generation and Function of Regulatory T Cells Through the Activation of Purinergic P2X Receptors

Purinergic signaling during inflammation converts immunosuppressive CD4+ T cells into proinflammatory ones. T Cells Lose Their Identity Regulatory T cells (Tregs) inhibit the actions of inflammatory T cells during immune responses and prevent autoimmunity. Schenk et al. showed that adenosine triphosphate (ATP) signaling through purinergic receptors on Tregs inhibited their immunosuppressive effects and exacerbated tissue inflammation in mice. Worse still, autocrine ATP signaling made the Tregs lose their identity, through the loss of their signature transcription factor Foxp3, and induced their conversion into proinflammatory, interleukin-17–secreting cells. These data suggest that ATP signaling through purinergic receptors might be an effective therapeutic target to shape immune responses, a suggestion supported by the maintenance of the identity and immunosuppressive function of Tregs through pretreatment with a purinergic receptor antagonist. Extracellular nucleotides are pleiotropic regulators of mammalian cell function. Adenosine triphosphate (ATP) released from CD4+ helper T cells upon stimulation of the T cell receptor (TCR) contributes in an autocrine manner to the activation of mitogen-activated protein kinase (MAPK) signaling through purinergic P2X receptors. Increased expression of p2rx7, which encodes the purinergic receptor P2X7, is part of the transcriptional signature of immunosuppressive CD4+CD25+ regulatory T cells (Tregs). Here, we show that the activation of P2X7 by ATP inhibits the suppressive potential and stability of Tregs. The inflammatory cytokine interleukin-6 (IL-6) increased ATP synthesis and P2X7-mediated signaling in Tregs, which induced their conversion to IL-17–secreting T helper 17 (TH17) effector cells in vivo. Moreover, pharmacological antagonism of P2X receptors promoted the cell-autonomous conversion of naïve CD4+ T cells into Tregs after TCR stimulation. Thus, ATP acts as an autocrine factor that integrates stimuli from the microenvironment and cellular energetics to tune the developmental and immunosuppressive program of the T cell in adaptive immune responses.
Comparison of Gene Expression of Umbilical Cord Vein and Bone Marrow–Derived Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) give origin to the marrow stromal environment that supports hematopoiesis. These cells present a wide range of differentiation potentials and a complex relationship with hematopoietic stem cells (HSCs) and endothelial cells. In addition to bone marrow (BM), MSCs can be obtained from other sites in the adult or the fetus. We isolate MSCs from the umbilical cord (UC) veins that are morphologically and immunophenotpically similar to MSCs obtained from the BM. In culture, these cells are capable of differentiating in vitro into adipocytes, osteoblasts, and condrocytes. The gene expression profiles of BM‐MSCs and of UC‐MSCs were compared by serial analysis of gene expression, then validated by reverse transcription polymerase chain reaction of selected genes. The two lineages shared almost all of the first thousand most expressed transcripts, including vimentin, galectin 1, osteonectin, collagens, transgelins, annexin A2, and MMP2. Nevertheless, a set of genes related to antimicrobial activity and to osteogenesis was more expressed in BM‐MSCs, whereas higher expression in UC‐MSCs was observed for genes that participate in pathways related to matrix remodeling via metalloproteinases and angiogenesis. Finally, cultured endothelial cells, CD34+ HSCs, MSCs, blood leukocytes, and bulk BM clustered together, separated from seven other normal nonhematopoietic tissues, on the basis of shared expressed genes. MSCs isolated from UC veins are functionally similar to BM‐MSCs, but differentially expressed genes may reflect differences related to their sites of origin: BM‐MSCs would be more committed to osteogenesis, whereas UC‐MSCs would be more committed to angiogenesis.
Schoolgirls and Soccer Moms: A Content Analysis of Free “Teen” and “MILF” Online Pornography

Viewing free online pornographic videos has increasingly become a common behavior among young people, although little is known about the content of these videos. The current study analyzed the content of two popular female-age-based types of free, online pornography (teen and MILF) and examined nuances in the portrayal of gender and access to power in relation to the age of the female actor. A total of 100 videos were selected from 10 popular Web sites, and their content was coded using independent raters. Vaginal intercourse and fellatio were the most frequently depicted sexual acts. The use of sex toys, paraphilias, cuddling, and condom use were rare, as were depictions of coercion. Control of the pace and direction of sexual activity was typically shared by the male and female actors. Moreover, there were no gender differences in initiation of sexual activity, use of persuasion, portrayals of sexual experience, or in professional status. However, female actors in MILF videos were portrayed as more agentic and were more likely to initiate sexual activity, control the pace of sexual activity, and have a higher professional status. Implications regarding the role of pornography in generating or reinforcing sexual norms or scripts are discussed.
Specific latent membrane protein 1 gene sequences in type 1 and type 2 Epstein‐Barr virus from nasopharyngeal carcinoma in Hong Kong

We reported previously that a characteristic Epstein‐Barr virus latent membrane protein 1 (EBV‐LMP1) gene was associated with nasopharyngeal carcinoma (NPC) in Hong Kong. It showed a 30 bp deletion at the carboxyl terminus with specific amino acid substitution Asp at codon 335 with reference to Gly in B95‐8 LMP1. This deletion variant Asp335 was present in over 90% of NPC biopsy specimens. The present study attempted to determine the whole encoding sequence of the LMP1 gene in different EBV isolates from NPC, and its relation with EBV types. We found that 92% (34/37) of primary NPC tumours harboured EBV‐1 and possessed the LMP1 deletion variant, of which 86% were Asp335 and 6% were Gly335. EBV‐2 was present in 8% (3/37) of tumours and all contained the retention variant of the LMP1 gene. Sequencing of the whole encoding region of the LMP1 gene revealed that the deletion variant Asp335 and deletion variant Gly335 carried similar sequences. They showed 43 common nucleotide substitutions in 41 codons with reference to B95‐8. The retention variant showed 52 base changes in 46 codons compared with B95‐8. The amino acid alterations in both the deletion and retention variants were mostly clustered at the transmembrane domain of the protein. Furthermore, half of the substitutions were common to both variants, suggesting a common evolutionary selection pressure. Nonetheless, the 2 LMP1 variants showed differences in nucleotide alterations and were associated with different EBV types, suggesting the presence of 2 distinct EBV strains in Hong Kong NPC. Int. J. Cancer 76:399–406, 1998. © 1998 Wiley‐Liss, Inc.
Direct Alteration of a Specific Inhibitory Circuit of the Hippocampus by Antidepressants

Correct brain functioning relies on the precise activity of a myriad of synapses assembling neurons in complex networks. In the hippocampus, highly diverse inhibitory circuits differently govern several physiologically relevant network activities. Particularly, perisomatic inhibition provided by specific interneurons was proposed to control emotional states, and could therefore be affected by mood disorders and their therapy. We found that both chronic and acute administration of two major antidepressants, imipramine and fluoxetine, strongly and directly altered GABA-mediated (GABAergic) hippocampal neurotransmission in mice and rats, independently of their effects on amine reuptake systems. These drugs affected GABA release from synapses formed by fast-spiking cells, but not interneurons expressing cannabinoid receptor type 1, resulting in the disruption of γ oscillations. This differential effect, shared by two types of antidepressants, suggests a new mechanism of action of these medications, and a possible role of perisomatic inhibition in depressive disorders.
Incidence of Type 1 Diabetes Mellitus in Turkish Children from the Southeastern Region of the Country: A Regional Report

Objective: Variability in the incidence of type 1 diabetes mellitus (T1DM) related to geographical region, ethnic background, gender, and age indicates a need for further epidemiological studies. To date, there are no reported studies on the incidence of T1DM in the pediatric age group from the Southeastern region of Turkey. To define the incidence, demographic and clinical characteristics of T1DM in children 0-14 years of age in Diyarbakir, one of the largest cities in the Southeast region of Turkey. Methods: Hospital files of patients with the diagnosis of T1DM were reviewed. Data of all patients diagnosed between 1 June 2010 and 31 May 2011 were evaluated. Population data on the 0-14 age group were obtained from the Turkish Statistical Institute (TSI) reports. Results: From a total of 41 T1DM patients, 24 (58.5%) were female (male: 41.5%) with a male/female ratio of 1.4. The overall annual incidence of T1DM was 7.2/105, being 8.7/105 in females and 5.7/105 in males. The peak incidence was found to occur at age 5-9 years in the girls and 10-14 years in the boys. Mean age at diagnosis was 8.1±3.8 years. Rate of presentation with diabetic ketoacidosis was 65.9%. Patients applied most frequently in spring and winter months. Conclusions: In this first T1DM incidence study on the pediatric age group in Diyarbakir, Turkey, T1DM incidence was found to be similar to that in countries with low-middle incidence. Conflict of interest:None declared.