Miracle-dz/UniFAR-FTUs huggingface dataset:
Rbgulation hormonale du transporteur du glucose rCpondant a l ’ insuline , GLUT 4 : nouvelles avancCes

BY C A L L U M LIVINGSTONE, F I O N A J . T H O M S O N , M A R G A R E T I . A R B U C K L E , I A N W. CAMPBELL, THOMAS J . JESS , SUSAN K A N E , COLIN MOYES, LISA M. P O R T E R , J A C Q U E L I N E E . R I C E , M I C H A E L J . S E A T T E R A N D GWYN W. G O U L D Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ
Enhanced detection of cytomegalovirus in confluent MRC-5 cells treated with dexamethasone and dimethyl sulfoxide

Optimum growth conditions for human cytomegalovirus (HCMV) include the use of subconfluent, actively growing cultures of human embryonic fibroblasts. Many clinical virology laboratories, however, use tissue culture cells from commercial sources. These cells are usually confluent, static cultures that tend to be less sensitive to viral infection. To determine whether dimethyl sulfoxide (DMSO) or dexamethasone (DEX), which are known enhancers of HCMV, facilitates the detection of the virus in confluent cells, we tested both HCMV AD169 and a number of clinical specimens suspected to contain HCMV on MRC-5 cells in both shell vials and conventional tube cultures. We found that, in the shell vial test, treatment of the cultures with either DMSO or DEX before and after inoculation increased the number of cells staining positive by three- to sixfold compared with untreated controls. Best results were obtained by pretreating the cultures with DEX alone and by treating the cultures with a combination of DEX and 1% DMSO postinfection. In the conventional MRC-5 culture tubes, treatment with the reagents resulted in the more rapid appearance of cytopathic effect and a more extensive infection of the cell sheet. The experimental findings indicate that the enhancing effect of DEX is attributable mainly to the increased production of a cellular mRNA during the period preceding viral infection.
Stimulation of the paraventricular nucleus modulates firing of neurons in the nucleus of the solitary tract

Duan, Yu-Fei, Irwin J. Kopin, and David S. Goldstein. Stimulation of the paraventricular nucleus modulates firing of neurons in the nucleus of the solitary tract. Am. J. Physiol. 277 (Regulatory Integrative Comp. Physiol. 46): R403–R411, 1999. —The present study assessed whether the baroreflex inhibition elicited by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) involves altered activity in the nucleus of the solitary tract (NTS). Unit recordings were made from 107 neurons in the NTS in anesthetized rabbits. Intravenous phenylephrine was used to induce a pressor response and to activate baroreflexes. Of the neurons that responded to pressor responses, two-thirds were excited and one-third was inhibited. Stimulation of the PVN inhibited 70% of the phenylephrine-responsive NTS neurons, with or without concurrent baroreceptor stimulation. When PVN stimulation was delivered concurrently with phenylephrine injection, more NTS neuronal inhibition and less excitation occurred than with phenylephrine alone. Usually PVN stimulation inhibited NTS neurons that were excited by pressor responses; less commonly, PVN stimulation excited NTS neurons that were inhibited by pressor responses. The findings are consistent with the view that PVN activation during the defense reaction inhibits baroreflexes by altering firing of NTS neurons.
HIV Self-Testing Increases HIV Testing Frequency in High-Risk Men Who Have Sex With Men: A Randomized Controlled Trial

Background: Self-testing may increase HIV testing and decrease the time people with HIV are unaware of their status, but there is concern that absence of counseling may result in increased HIV risk. Setting: Seattle, Washington. Methods: We randomly assigned 230 high-risk HIV-negative men who have sex with men to have access to oral fluid HIV self-tests at no cost versus testing as usual for 15 months. The primary outcome was self-reported number of HIV tests during follow-up. To evaluate self-testing's impact on sexual behavior, we compared the following between arms: non–HIV-concordant condomless anal intercourse and number of male condomless anal intercourse partners in the last 3 months (measured at 9 and 15 months) and diagnosis with a bacterial sexually transmitted infection (STI: early syphilis, gonorrhea, and chlamydial infection) at the final study visit (15 months). A post hoc analysis compared the number of STI tests reported during follow-up. Results: Men randomized to self-testing reported significantly more HIV tests during follow-up (mean = 5.3, 95% confidence interval = 4.7 to 6.0) than those randomized to testing as usual (3.6, 3.2 to 4.0; P < 0.0001), representing an average increase of 1.7 tests per participant over 15 months. Men randomized to self-testing reported using an average of 3.9 self-tests. Self-testing was noninferior with respect to all markers of HIV risk. Men in the self-testing arm reported significantly fewer STI tests during follow-up (mean = 2.3, 95% confidence interval = 1.9 to 2.7) than men in the control arm (3.2, 2.8 to 3.6; P = 0.0038). Conclusions: Access to free HIV self-testing increased testing frequency among high-risk men who have sex with men and did not impact sexual behavior or STI acquisition.
Beyond type 2 diabetes: sodium glucose co‐transporter‐inhibition in type 1 diabetes

Use of sodium glucose cotransporter (SGLT) inhibitors are a well‐established therapeutic option in type 2 diabetes (T2D) with a variety of proven therapeutic benefits. They have become a pillar of current treatment guidelines. In type 1 diabetes (T1D), initial exploratory studies have shown benefits in glycemic control, weight control, and cardiovascular risk parameters, leading to trials aiming for regulatory submission with several agents. Results from four 1‐year trials, which included a total of 3052 patients, are now available, demonstrating promising findings that target the unmet needs of patients with T1D with a novel insulin‐independent adjunct therapy. However, these positive effects must be balanced against the risks associated with this class of drugs. Specifically, current T1D studies have shown an increased risk of diabetic ketoacidosis (DKA), which, in some cases, presented with only slightly elevated glucose levels. While this complication may be clinically manageable once detected, the metabolic shift towards ketogenesis associated with this class of agents mandates appropriate patient selection. Currently, there are no validated tools for DKA risk assessment. Although the experience gained in studies and off‐label use provides some indication for appropriate patient selection, this would have to be evaluated closely in the event that these drugs would receive regulatory approval. Risk mitigation includes training in ketone measurement (preferably as blood β‐hydroxybutyrate testing), teaching the concept of euglycemic DKA, and providing a clear treatment algorithm to avoid progression of ketosis to full‐blown DKA. Because similar unmet needs also exist in pediatric population studies, risk mitigation in youth should be initiated as well to allow an evidence‐based, risk‐benefit assessment in this vulnerable population.
Behçet's Syndrome as a Model of Thrombo-Inflammation: The Role of Neutrophils

Behçet's syndrome (BS) is a systemic vasculitis, clinically characterized by different organ involvement and often complicated by thrombosis which occurs in vessels of all sizes. Thrombosis is more frequent in male patients with active disease and represents an important cause of morbidity and mortality. Neutrophil involvement in BS has been repeatedly suggested in the last few years. Indeed, neutrophils have been shown to be hyperactivated in BS patients, probably with a HLAB51 related contribution, and represent the main cells infiltrating not only oral and genital ulcers or erythema nodosum, but also other sites. Besides being deputed to host defense against micro-organisms, neutrophils display fundamental roles both in inflammation and tissue damage becoming inappropriately activated by cytokines, chemokines and autoantibodies and subsequently producing large amounts of superoxide anion (O2.) via NADPH oxidase (NOX2). The strict relationship between inflammation and hemostasis has been already demonstrated. Indeed, inflammation and immune-mediated disorders increase the risk of thrombosis, but the pathways that link these processes have not been completely elucidated. In this regard, we recently demonstrated, in a large population of BS patients, a new neutrophil-dependent pathogenetic mechanism of thrombosis. In particular, it was shown that neutrophils, mainly through NADPH oxidase, produce excessive amounts of reactive oxygen species (ROS), which are able to markedly modify the secondary structure of fibrinogen and hence the overall architecture of the fibrin clot that becomes less susceptible to plasmin-induced lysis. These data point out that BS represents “per se” a model of inflammation-induced thrombosis and suggest that neutrophils specifically contribute to thrombo-inflammation in this rare disease. In particular, it is suggested that an alteration in fibrinogen structure and function are associated with enhanced ROS production via neutrophil NADPH oxidase. Altogether, these findings improve our understanding of the intricate pathogenetic mechanisms of thrombo-inflammation and may indicate potential new therapeutic targets.
Impact of Hunger, Satiety, and Oral Glucose on the Association Between Insulin and Resting-State Human Brain Activity

To study the interplay of metabolic state (hungry vs. satiated) and glucose administration (including hormonal modulation) on brain function, resting-state functional magnetic resonance imaging (rs-fMRI) and blood samples were obtained in 24 healthy normal-weight men in a repeated measurement design. Participants were measured twice: once after a 36 h fast (except water) and once under satiation (three meals/day for 36 h). During each session, rs-fMRI and hormone concentrations were recorded before and after a 75 g oral dose of glucose. We calculated the amplitude map from blood-oxygen-level-dependent (BOLD) signals by using the fractional amplitude of low-frequency fluctuation (fALFF) approach for each volunteer per condition. Using multiple linear regression analysis (MLRA) the interdependence of brain activity, plasma insulin and blood glucose was investigated. We observed a modulatory impact of fasting state on intrinsic brain activity in the posterior cingulate cortex (PCC). Strikingly, differences in plasma insulin levels between hunger and satiety states after glucose administration at the time of the scan were negatively related to brain activity in the posterior insula and superior frontal gyrus (SFG), while plasma glucose levels were positively associated with activity changes in the fusiform gyrus. Furthermore, we could show that changes in plasma insulin enhanced the connectivity between the posterior insula and SFG. Our results indicate that hormonal signals like insulin alleviate an acute hemostatic energy deficit by modifying the homeostatic and frontal circuitry of the human brain.
CHITINASE LIKE1 Regulates Root Development of Dark-Grown Seedlings by Modulating Ethylene Biosynthesis in Arabidopsis thaliana

The plant hormone ethylene plays a regulatory role in development in light- and dark-grown seedlings. We previously isolated a group of small-molecule compounds with a quinazolinone backbone, which were named acsinones (for ACC synthase inhibitor quinazolinones), that act as uncompetitive inhibitors of 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS). Thus, the triple response phenotype, which consists of shortened hypocotyls and roots, radial swelling of hypocotyls and exaggerated curvature of apical hooks, was suppressed by acsinones in dark-grown (etiolated) ethylene overproducer (eto) seedlings. Here, we describe our isolation and characterization of an Arabidopsis revert to eto1 9 (ret9) mutant, which showed reduced sensitivity to acsinones in etiolated eto1 seedlings. Map-based cloning of RET9 revealed an amino acid substitution in CHITINASE LIKE1 (CTL1), which is required for cell wall biogenesis and stress resistance in Arabidopsis. Etiolated seedlings of ctl1ret9 showed short hypocotyls and roots, which were augmented in combination with eto1-4. Consistently, ctl1ret9 seedlings showed enhanced sensitivity to exogenous ACC to suppress primary root elongation as compared with the wild type. After introducing ctl1ret9 to mutants completely insensitive to ethylene, genetic analysis indicated that an intact ethylene response pathway is essential for the alterations in root and apical hook but not hypocotyl in etiolated ctl1ret9 seedlings. Furthermore, a mild yet significantly increased ethylene level in ctl1 mutants was related to elevated mRNA level and activity of ACC oxidase (ACO). Moreover, genes associated with ethylene biosynthesis (ACO1 and ACO2) and response (ERF1 and EDF1) were upregulated in etiolated ctl1ret9 seedlings. By characterizing a new recessive allele of CTL1, we reveal that CTL1 negatively regulates ACO activity and the ethylene response, which thus contributes to understanding a role for ethylene in root elongation in response to perturbed cell wall integrity.
A QoS approach for cluster-based routing in VANETS using TDMA scheme

In an effort to provide QoS in VANET, the IEEE 802.11p physical layer, which is recommended as VANET MAC protocol experiences a huge amount of packet losses as a result of collisions. Its performance can be improved by using Time Division Multiple Access (TDMA) scheme to attain restructuring of TDMA slots with no central control. In this paper, we intend to propose a QoS routing protocol capable of finding and establishing a path through clustering approach using TDMA. This, however, is achieved by calculating the corresponding QoS provision values based on QoS metrics before selecting the optimal, reliable and stable route between source, cluster head and destination. The protocol would be an extension of LORA-CBF, to which QoS features are embedded in the route request selection. The results obtained through NCTUns simulator are used for analysis of throughput for both UDP and TCP traffic classes.
Protein Glycosylation and Tumor Microenvironment Alterations Driving Cancer Hallmarks

Decades of research have disclosed a plethora of alterations in protein glycosylation that decisively impact in all stages of disease and ultimately contribute to more aggressive cell phenotypes. The biosynthesis of cancer-associated glycans and its reflection in the glycoproteome is driven by microenvironmental cues and these events act synergistically toward disease evolution. Such intricate crosstalk provides the molecular foundations for the activation of relevant oncogenic pathways and leads to functional alterations driving invasion and disease dissemination. However, it also provides an important source of relevant glyco(neo)epitopes holding tremendous potential for clinical intervention. Therefore, we highlight the transversal nature of glycans throughout the currently accepted cancer hallmarks, with emphasis on the crosstalk between glycans and the tumor microenvironment stromal components. Focus is also set on the pressing need to include glycans and glycoconjugates in comprehensive panomics models envisaging molecular-based precision medicine capable of improving patient care. We foresee that this may provide the necessary rationale for more comprehensive studies and molecular-based intervention.
Marine Sediment Mixed With Activated Carbon Allows Electricity Production and Storage From Internal and External Energy Sources: A New Rechargeable Bio-Battery With Bi-Directional Electron Transfer Properties

Marine sediment has a great potential to generate electricity with a bioelectrochemical system (BES) like the microbial fuel cell (MFC). In this study, we investigated the potential of marine sediment and activated carbon (AC) to generate and store electricity. Both internal and external energy supply was validated for storage behavior. Four types of anode electrode compositions were investigated. Two types were mixtures of different volumes of AC and Dutch Eastern Scheldt marine sediment (67% AC and 33% AC) and the others two were 100% AC or 100% marine sediment based. Each composition was duplicated. Operating these BES’s under MFC mode with solely marine sediment as the anode electron donor resulted in the creation of a bio-battery. The recharge time of such bio-battery does depend on the fuel content and its usage. The results show that by usage of marine sediment and AC electricity was generated and stored. The 100% AC and the 67% AC mixed with marine sediment electrode were over long term potentiostatic controlled at -100 mV vs. Ag/AgCl which resulted in a cathodic current and an applied voltage. After switching back to the MFC operation mode at 1000 Ω external load, the electrode turned into an anode and electricity was generated. This supports the hypothesis that external supply electrical energy was recovered via bi-directional electron transfer. With open cell voltage experiments these AC marine bioanodes showed internal supplied electric charge storage up to 100 mC at short self-charging times (10 and 60 s) and up to 2.4°C (3,666 C/m3 anode) at long charging time (1 h). Using a hypothetical cell voltage of 0.2 V, this value represents an internal electrical storage density of 0.3 mWh/kg AC marine anode. Furthermore it was remarkable that the BES with 100% marine sediment based electrode also acted like a capacitor similar to the charge storage behaviors of the AC based bioanodes with a maximum volumetric storage of 1,373 C/m3 anode. These insights give opportunities to apply such BES systems as e.g., ex situ bio-battery to store and use electricity for off-grid purpose in remote areas.
General and ICT Self-Efficacy in Different Participants Roles in Cyberbullying/Victimization Among Pakistani University Students

The study examines both general and Internet and Communication Technology (ICT) self-efficacy in cyber-victims, cyber-bullies, and cyber bully victims in comparison to un-involved students. Gender differences were also examined. A total of 1115 Pakistani university students from six universities participated in the study. Analyses were conducted on 950 complete cases (371 males, and 579 females). Data were collected on cyberbullying/victimization, general self-efficacy (GSE), ICT self-efficacy, traditional bullying/victimization, ICT usage, social desirability, and demographics. Multinomial logistic regression analysis indicated that ICT self-efficacy significantly decreased the probability of being a cyber-victim and significantly increased the chances of being a cyber-bully whereas GSE appeared to have no role in predicting participant roles in cyberbullying after controlling for covariates (i.e., age, gender, traditional bullying, traditional victimization, social desirability, Internet usage, time spent on the Internet, and social networking sites (SNS). Findings of the study have important implications for developing and enhancing interventions with respect to the inclusion of ICT related skills in anti-cyberbullying programs. With respect to gender, findings showed that females reported a higher level of victimization while males reported higher perpetration on both traditional and cyberbullying.
The Epigenomics of Pituitary Adenoma

Background: The vast majority of pituitary tumors are benign and behave accordingly; however, a fraction are invasive and are more aggressive, with a very small fraction being frankly malignant. The cellular pathways that drive transformation in pituitary neoplasms are poorly characterized, and current classification methods are not reliable correlates of clinical behavior. Novel techniques in epigenetics, the study of alterations in gene expression without changes to the genetic code, provide a new dimension to characterize tumors, and may hold implications for prognostication and management. Methods: We conducted a review of primary epigenetic studies of pituitary tumors with a focus on histone modification, DNA methylation, and transcript modification. Results: High levels of methylation have been identified in invasive and large pituitary tumors. DNA methyltransferase overexpression has been detected in pituitary tumors, especially in macroadenomas. Methylation differences at CpG sites in promoter regions may distinguish several types of tumors from normal pituitary tissue. Histone modifications have been linked to increased p53 expression and longer progression-free survival in pituitary tumors; sirtuins are expressed at higher values in GH-expressing compared to nonfunctional adenomas and correlate inversely with size in somatotrophs. Upregulation in citrullinating enzymes may be an early pathogenic marker of prolactinomas. Numerous genes involved with cell growth and signaling show altered methylation status for pituitary tumors, including cell cycle regulators, components of signal transduction pathways, apoptotic regulators, and pituitary developmental signals. Conclusions: The limited clinical predictive capacity of the current pituitary tumor classification system suggests that tumor subclasses likely remain to be discovered. Ongoing epigenetic studies could provide a basis for adding methylation and/or acetylation screening to standard pituitary tumor workups. Identifying robust correlations between tumor epigenetics and corresponding histological, radiographic, and clinical course information could ultimately inform clinical decision-making.
Comparison of Quantamatrix Multiplexed Assay Platform and GenoType MTBDR Assay Using Smear-Positive Sputum Specimens From Patients With Multidrug- Resistant/Extensively Drug-Resistant Tuberculosis in South Korea

Rapid detection of drug-resistant tuberculosis (DR-TB) is crucial for timely treatment and management. The GenoType MTBDRplus and MTBDRsl (MTBDR) assays have been endorsed by the World Health Organization (WHO) for the detection of DR-TB. However, MTBDR assays cannot simultaneously detect multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Furthermore, interpretation of the MTBDR assay requires trained people, and the assay has low sample throughput, processing only up to 12 samples in parallel. We have developed the Quantamatrix Multiplexed Assay Platform (QMAP) to detect MDR-/XDR-TB simultaneously. The interpretation of QMAP results is automated, and the platform can process up to 96 samples in parallel. To compare the performance of QMAP with MTBDR assays, we performed QMAP and the MTBDR assay on 76 smear-positive, Mycobacterium tuberculosis culture-positive sputum specimens. Compared with phenotypic drug susceptibility testing (DST) results, the sensitivity and specificity of QMAP were 100 and 98% for rifampin resistance, 80 and 100% for isoniazid resistance, 44.4 and 100% for ethambutol resistance, 100 and 100% for fluoroquinolone resistance, and 100 and 100% for second-line injectable drug resistance, respectively. The sensitivity and specificity of MTBDR assays were 100 and 98% for rifampin resistance, 80 and 100% for isoniazid resistance, 44.4 and 98.1% for ethambutol resistance, 100 and 100% for fluoroquinolone resistance, and 100 and 100% for second-line injectable drug resistance, respectively. The sensitivity and specificity of QMAP were 85.0 and 100%, respectively, for the detection of MDR-TB and 100 and 100%, respectively, for XDR-TB. The sensitivity and specificity of MTBDR assays was consistent with those of QMAP. Our study showed that the QMAP assay has sensitivity and specificity equivalent to that of MTBDR assays in smear-positive sputum specimens. In combination with phenotypic DST, QMAP might be useful as a supplementary DST assay for rapid detection of MDR-/XDR-TB.