Miracle-dz/UniFAR-FTUs huggingface dataset:
CD40 Engagement on Endothelial Cells Promotes Tissue Factor-dependent Procoagulant Activity

Summary The CD40 molecule expressed on endothelial cells has been shown to transduce activation signals resulting in upregulation of adhesion molecules. Herein, we studied the impact of CD40 engagement on the induction of tissue factor (TF)-dependent procoagulant activity (PCA) at the surface of human umbilical vein endothelial cells (HUVECs). First, we found that co-incubation of HUVECs with 3T6 fibroblasts transfected with the CD40L gene (3T6-CD40L) resulted in a clear induction of PCA which was not observed with control untransfected fibroblasts. The specificity of this finding was established by inhibition experiments using monoclonal antibodies (mAbs) blocking CD40 or CD40L. PCA induced by CD40 ligation was TF-related as it was not observed in factor VII-deficient plasma and was associated with the accumulation of TF mRNA. To investigate the role of CD40/CD40L interactions in the induction of endothelial cell PCA by lymphocytes, interferon (IFN)-γ-stimulated EC were incubated with T cells in the absence or presence of anti-CD40 or anti-CD40L mAb. The 60-70% inhibition of PCA induced by these mAbs but not their isotype-matched control indicated that the CD40 pathway is involved in the induction of PCA resulting from interactions between activated HUVECs and T cells. We conclude that activation signals elicited by CD40 engagement on endothelial cells result in the induction of TF-dependent PCA. The CD40/CD40L pathway might therefore be involved in the development of prothrombic states during diseases associated with endothelial cell and T cell activation.
Testosterone Is Significantly Reduced in Endurance Athletes without Impact on Bone Mineral Density

Aims: To compare the basal plasma reproductive hormonal profile in three groups of athletes involved in different training programs, and to define the relationship between androgen level and bone mineral density (BMD) in male athletes. Methods: Basal serum total testosterone (TT), free androgen index (FAI), sex hormone-binding globulin (SHBG), cortisol, cortisol to TT ratio, luteinizing hormone (LH), estrogen and BMD were evaluated in cyclists (CY; n = 11), triathletes (TR; n = 14) and swimmers (SW; n = 13) and compared with less active controls (n = 10). Results: TT and FAI levels were lower (p < 0.05) in CY and TR, whereas the ratio of cortisol to TT was increased in CY only (p < 0.05). No alteration in serum LH, SHBG, estrogen or cortisol concentration was observed. BMD was higher in the proximal femur in TR (p < 0.05). No BMD or hormonal differences were found in SW. Conclusion: Only the endurance training of CY and TR induced androgen deficiency without apparent alteration of BMD.
Follicular CD8+ T Cells: Origin, Function and Importance during HIV Infection

The lymphoid follicle is critical for the development of humoral immune responses. Cell circulation to this site is highly regulated by the differential expression of chemokine receptors. This feature contributes to the establishment of viral reservoirs in lymphoid follicles and the development of some types of malignancies that are able to evade immune surveillance, especially conventional CD8+ T cells. Interestingly, a subtype of CD8+ T cells located within the lymphoid follicle (follicular CD8+ T cells) was recently described; these cells have been proposed to play an important role in viral and tumor control, as well as to modulate humoral and T follicular helper cell responses. In this review, we summarize the knowledge on this novel CD8+ T cell population, its origin, function, and potential role in health and disease, in particular, in the context of the infection by the human immunodeficiency virus.
Context aware and pattern oriented machine learning framework(CAPOMF) for Android

Context-aware computing refers to a very peculiar kind of application that can sense the physical environment and behave accordingly. This feature of context awareness can be further enhanced using machine learning. This is possible by providing services not only related to the usage pattern of the users but also the environmental context of the user. Android being one of the most popular mobile platform has constantly addressed context awareness through hardware and software support. This paper evaluates the Android platform and also proposes a framework that incorporates context-aware services along with machine learning capability in order to provide a one of a kind pattern oriented framework that not only aids in development of applications but also utilizes the hardware support of sensors of the Android hardware system to utilize the full potential of the mobile platform. Finally this paper also evaluates the framework by building an application that helps to solve the transit problems arising due to potholes present in the streets of Mumbai. The application built effectively maps the locations of such potholes and helps commuters avoid such potholes and thus saves the repair costs of vehicles.
Ubiquitin Carboxyl-Terminal Hydrolase L1, a Novel Deubiquitinating Enzyme in the Vasculature, Attenuates NF-&kgr;B Activation

Objective— We identified a ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene, which encodes a deubiquitinating enzyme and is expressed in the vasculature, by functional screening of a human endothelial cell (EC) cDNA library. UCHL1 is expressed in neurons, and abnormalities in UCHL1 are responsible for inherited Parkinson’s disease via its effects on the ubiquitin-proteasome system. Therefore, the goal of present study was to clarify the role of the UCHL1 gene in vascular remodeling by evaluating nuclear factor-&kgr;B (NF-&kgr;B) inactivation in ECs and vascular smooth muscle cells (VSMCs). Methods and Results— From Northern blot and immunohistochemical analysis, the UCHL1 gene was endogenously expressed in vascular ECs, VSMCs, and brain tissue. Expression of UCHL1 was markedly increased in the neointima of the balloon-injured carotid artery and was also present in atherosclerotic lesions from human carotid arteries. Overexpression of the UCHL1 gene significantly attenuated tumor necrosis factor (TNF)-α–induced NF-&kgr;B activity in vascular cells and increased inhibitor of kappa B-α (I&kgr;B-α), possibly through the attenuation of I&kgr;B-α ubiquitination, leading to decreased neointima in the balloon-injured artery. In contrast, knockdown of UCHL1 by small interfering RNA resulted in increased NF-&kgr;B activity in VSMCs. Conclusions— These data suggest that UCHL1 may partially attenuate vascular remodeling through inhibition of NF-&kgr;B activity.
Importance of membrane‐proximal N‐glycosylation on integrin α1 in its activation and complex formation

N‐Glycosylation of integrin α5β1 plays important roles in cell biologic functions; however, the mechanisms that underlie those roles remain poorly understood. Here, we present evidence that themembrane‐proximal N‐glycosylation on integrin β1 could positively regulate cell migration by promoting β1 activation. The S4–6 β1 mutant contains only 3 N‐glycosylation sites, which are essential for α5 and β1 heterodimer formation, and despite only a small difference in expression levels of α5β1 between wild‐type and S4–6 mutant, cell spreading and migration of the S4–6 mutant was significantly decreased compared with that of control. Consistent with these phenotypes, β1 ‐mediated cellular signaling and its activation were clearly suppressed in the S4–6 mutant. Of note, these developments could be rescued by restoration of N‐glycosylation sites in the membrane‐proximal domain. Further study on the regulatory mechanisms suggested that membrane‐proximal N‐glycosylation is critical for intermolecular interactions between integrin β1 and other cell membrane proteins, such as syndecan‐4 and epidermal growth factor receptor. Moreover, α2, 6‐sialylation is required for β1 activation. These data suggest a novel regulatory mechanism where in N‐glycosy lationnear the cell membrane on β1 may serve as a platform that facilitates its complex formation on the cell membrane, thereby affecting integrin‐mediated functions. —Hou, S. , Hang, Q. , Isaji, T. , Lu, J., Fukuda, T. , Gu, J. Importance ofmembrane‐proximal N‐glycosylation on integrin β1 in its activation and complex formation. FASEB J. 30, 4120–4131 (2016). www.fasebj. org
Headgroup-specific Exposure of Phospholipids in ABCA1-expressing Cells*

ABCA1 has been established to be required for the efflux of cholesterol and phospholipids to apolipoproteins such as apoA-I. At present, it is unclear whether ABCA1-mediated lipid exposure is specific with regard to lipid headgroups and whether it requires calcium activation and the presence of a lipid acceptor. In the present work, we found exofacial exposure of endogenous phosphatidylserine in the absence of apoA-I to be enhanced in ABCA1-GFP expressing MDCKII and HeLa cells compared with control cells. By using C6-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) (NBD)-labeled phospholipid analogues, we observed elevated redistribution of phosphatidylserine and phosphatidylethanolamine but not of phosphatidylcholine analogues from the cytoplasmic to the exoplasmic leaflet of the plasma membrane of ABCA1-GFP expressing cells. Whereas glyburide affected neither the level of exofacial endogenous PS nor the outward movement of the amino phospholipid analogues, the latter was sensitive to intracellular Ca2+ in ABCA1-GFP expressing cells, further enhancing outward analogue redistribution with respect to control cells. Both receptor-mediated endocytosis and fluidphase endocytosis were reduced in MDCKII cells expressing ABCA1-GFP. Glyburide raised the level of receptor-mediated endocytosis in the ABCA1-GFP expressing cell to the level of control cells in the absence of glyburide. In control cells, however, fluid-phase endocytosis but not receptor-mediated endocytosis was significantly reduced upon glyburide treatment.
Evaluation of Two Protocols of Uremic Rat Model: Partial Nephrectomy and Infarction

Animal models of chronic renal failure have been mostly achieved by partial ablation of renal parenchyma, the two most common techniques employed being surgical resection or infarction. Evaluation of the uremic model using these two techniques was carried out in Wistar rats. Two weeks after operative procedure, measured serum urea levels in the resection and infarction models were 59.1 and 64.3 mg/dL (normal range 15.6–24.4 mg/dL) respectively. However, the standard deviation in the former was significantly lower, 6.3 vs. 97.1 mg/dL from infarction model, p = 0.007. A consistent degree of glomerular filtration rate reduction was obtained in the resection model, resulting in 20–30% of normal creatinine clearance. This compared favorably with the creatinine clearance range (0.3–74% of normal) from the infarction model, in which two animals died of uremia and seven had higher than 50% of normal creatinine clearance. It is reasonable to attribute reproducibility and homogeneity demonstrated in the resection model to (i) more precise control of renal ablation extent with surgical techniques and (ii) less interplay of confounding injury mechanism to remnant kidney. These data support superiority of the resection model as an experimental tool for pathophysiological and/or interventional investigations of chronic renal failure.
`Eph'ective signaling: forward, reverse and crosstalk

The Eph receptors comprise the largest group of receptor tyrosine kinases and are found in a wide variety of cell types in developing and mature tissues. Their ligands are the ephrins, a family of membrane-bound proteins found in lipid rafts. In the past decade, Eph receptors and ephrins have been implicated in a vast array of cellular processes. Unlike other receptor tyrosine kinases, however, the Eph receptors seem to be geared towards regulating cell shape and movement rather than proliferation. Studies have uncovered intricate signaling networks that center around the ligand-receptor complex, and this may account for the broad repertoire of functions of Eph proteins. Deciphering the bi-directional pathways emanating from an Eph receptor-ephrin complex will not only help us to understand basic biological processes, but may also provide important insight into disease.
Serum Interleukin-8 is Elevated in Men with Prostate Cancer and Bone Metastases

Aalinkeel et al. (1) have recently reported that gene expression of angiogenic factors correlates with metastatic potential of prostate cancer cells. The rationale for the study of Aalinkeel et al. is that a variety of growth factors, among them interleukin-8 (il-8), can induce angiogenesis (2). Further, parathyroid hormone related peptide (PTHrP) acts to induce il-8 production in prostate cancer cells via an intracrine pathway independent of its classical nuclear localization sequence. This novel pathway could mediate the effects of PTHrP on the progression of prostate cancer (3). We measured il-8 in the serum of 39 men with biopsy-proven prostate cancer. Their average age was 69 +/- 9 (mean +/- SD). Serum il-8 was measured with an automated chemiluminometric high sensitivity il-8 protein assay (Immulite, Diagnostic Products Corporation, Los Angeles, CA). We noted a significant elevation of il-8 in men with bone metastases, diagnosed by Tc-99 MDP bone scan, when compared to men with localized disease (Figure 1). Aalinkeel et al. found that il-8 was significantly higher in the more metastatic PC-3 and DU-145 prostate cancer cell lines, when compared to the poorly metastatic LnCAP cells. The results of our study of il-8 in men with prostate cancer support the findings of Aalinkeel et al. Therefore, new anti-angiogenic therapies targeting specific genes controlling prostate tumor metastasis may be of benefit in treating prostate cancer.
Model ARIAS berbasis TSTS terhadap Kemampuan Berpikir Kritis Matematis Ditinjau dari Gaya Kognitif

This study aims to determine whether there is the influence of ARIAS model based on Two Stay Two Stray model to critical thinking ability mathematically. This research is Quasi-Experimental Design research. Hypothesis testing using variance analysis of two different cell roads Based on the test of cell variance analysis is not the same obtained that there is influence of ARIAS model based on Two Stay Two Stray to critical mathematical thinking ability and there is influence of cognitive style to critical thinking skill mathematically, where student with treatment of learning using integrated learning model ARIAS TSTS learning model on the ability of critical thinking is better than students with learning treatment using lecture methods in terms of each student's cognitive style. The students' mathematical critical thinking ability with independent field cognitive style is better than students with cognitive field dependent style. There is no interaction between learning and cognitive styles to critical mathematical thinking skills.
Dynamics and efficiency in vivo of UGA‐directed selenocysteine insertion at the ribosome

The kinetics and efficiency of decoding of the UGA of a bacterial selenoprotein mRNA with selenocysteine has been studied in vivo. A gst–lacZ fusion, with the fdhF SECIS element ligated between the two fusion partners, gave an efficiency of read‐through of 4–5%; overproduction of the selenocysteine insertion machinery increased it to 7–10%. This low efficiency is caused by termination at the UGA and not by translational barriers at the SECIS. When the selenocysteine UGA codon was replaced by UCA, and tRNASec with anticodon UGA was allowed to compete with seryl‐tRNASer1 for this codon, selenocysteine was found in 7% of the protein produced. When a non‐cognate SelB–tRNASec complex competed with EF‐Tu for a sense codon, no effects were seen, whereas a non‐cognate SelB–tRNASec competing with EF‐Tu‐mediated Su7‐tRNA nonsense suppression of UGA interfered strongly with suppression. The induction kinetics of β‐galactosidase synthesis from fdhF′–′lacZ gene fusions in the absence or presence of SelB and/or the SECIS element, showed that there was a translational pause in the fusion containing the SECIS when SelB was present. The results show that decoding of UGA is an inefficient process and that using the third dimension of the mRNA to accommodate an additional amino acid is accompanied by considerable quantitative and kinetic costs.
Viral Inhibition of IL-1- and Neutrophil Elastase-Induced Inflammatory Responses in Bronchial Epithelial Cells1

Previously, we elucidated the intracellular mechanisms by which neutrophil elastase (NE) up-regulates inflammatory gene expression in bronchial epithelial cells. In this study, we examine the effects of both IL-1 and NE on inflammatory gene expression in 16HBE14o− bronchial epithelial cells and investigate approaches to abrogate these inflammatory responses. IL-1 induced IL-8 protein production in time- and dose-dependent fashions, an important observation given that IL-8 is a potent neutrophil chemoattractant and a key inflammatory mediator. IL-1 and NE were shown to activate the p38 MAPK pathway in 16HBE14o− cells. Western blot analysis demonstrated IL-1R-associated kinase 1 (IRAK-1) degradation in response to stimulation with both IL-1 and NE. In addition, the expression of dominant negative IRAK-1 (IRAK-1Δ), IRAK-2Δ, or IRAK-4Δ inhibited IL-1- and NE-induced NF-κB-linked reporter gene expression. Dominant negative versions of the intracellular adaptor proteins MyD88 (MyD88Δ) and MyD88 adaptor-like (Mal P/H) abrogated NE-induced NF-κB reporter gene expression. In contrast, only MyD88Δ was found to inhibit IL-1-induced NF-κB reporter activity. We also investigated the vaccinia virus proteins, A46R and A52R, which have been shown to antagonize IL-1 signaling. Transfection with A46R or A52R cDNA inhibited IL-1- and NE-induced NF-κB and IL-8R gene expression and IL-8 protein production in primary and transformed bronchial epithelial cells. Furthermore, cytokine array studies demonstrated that IL-1 and NE can up-regulate the expression of IL-6, oncostatin M, epithelial cell-derived neutrophil activating peptide-78, growth-related oncogene family members, vascular endothelial growth factor, and GM-CSF, with induction of these proteins inhibited by the viral proteins. These findings identify vaccinia virus proteins as possible therapeutic agents for the manifestations of several inflammatory lung diseases.
Neuronal Glutamine Utilization: Pathways of Nitrogen Transfer tudied with [15N]Glutamine

Abstract: Gas chromatography‐mass spectrometry was used to evaluate the metabolism of [I5N]glutamine in isolated rat brain synaptosomes. In the presence of 0.5 mM glutamine, synaptosomes accumulated this amino acid to a level of 25‐35 nmol/mg protein at an initial rate >9 nmol/min/mg of protein. The metabolism of [15NJglutamine generated l5N‐labelled glutamate, aspartate, and γ‐aminobutyric acid (GABA). An efflux of both [15N]gIutamate and [15N]aspartate from synaptosomes to the medium was observed. Enrichment of ,5N in alanine could not be detected because of a limited pool size. Elimination of glucose from the incubation medium substantially increased the rate and amount of [15N]aspartate formed. It is concluded that: (1) With 0.5 mM external glutamine, the glutaminase reaction, and not glutamine transport, determines the rate of metabolism of this amino acid. (2) The primary route of glutamine catabolism involves aspartate aminotransferase which generates 2‐oxoglutarate, a substrate for the tricarboxylic acid cycle. This reaction is greatly accelerated by the omission of glucose. (3) Glutamine has preferred access to a population of synaptosomes or to a synaptosomal compartment that generates GABA. (4) Synaptosomes maintain a constant internal level of glutamate plus aspartate of about 70‐80 nmol/mg protein. As these amino acids are produced from glutamine in excess of this value, they are released into the medium. Hence synaptosomal glutamine and glutamate metabolism are tightly regulated in an interrelated manner.
Neoplastic transformation by truncated alleles of human NOTCH1/TAN1 and NOTCH2

The Notch genes of Drosophila melanogaster and vertebrates encode transmembrane receptors that help determine cell fate during development. Although ligands for Notch proteins have been identified, the signaling cascade downstream of the receptors remains poorly understood. In human acute lymphoblastic T-cell leukemia, a chromosomal translocation damages the NOTCH1 gene. The damage apparently gives rise to a constitutively activated version of NOTCH protein. Here we show that a truncated version of NOTCH1 protein resembling that found in the leukemic cells can transform rat kidney cells in vitro. The transformation required cooperation with the E1A oncogene of adenovirus. The transforming version of NOTCH protein was located in the nucleus. In contrast, neither wild-type NOTCH protein nor a form of the truncated protein permanently anchored to the plasma membrane produced transformation in vitro. We conclude that constitutive activation of NOTCH similar to that found in human leukemia can contribute to neoplastic transformation. Transformation may require that the NOTCH protein be translocated to the nucleus. These results sustain a current view of how Notch transduces a signal from the surface of the cell to the nucleus.
Levels of Dissociation and Nonsuicidal Self-Injury: A Quartile Risk Model

Extant research indicates that dissociation may act as a risk factor for nonsuicidal self-injury (NSSI), but the data are mixed. In this study, 75 university and community females ages 18–35 were assessed for rates of normative, clinical, and severely clinical dissociation as well as for NSSI. Significant differences in normative dissociation were found between the control group and the group reporting a history of NSSI. In addition, normative dissociation—but not clinical or severely clinical dissociation—was found to be significantly associated with NSSI in this sample. Considering this finding in the context of the existing literature, we propose a quartile risk model of dissociation and NSSI as a new approach to the influences of levels of dissociation on NSSI risk.