Miracle-dz/UniFAR-FTUs huggingface dataset:
An Interferon- α -Induced Tethering Mechanism Inhibits HIV-1 and Ebola Virus Particle Release but Is Counteracted by the HIV-1 Vpu Protein Cell Host Microbe.

SUMMARY Type 1 interferon (IFN) inhibits the release of HIV-1 virus particles via poorly defined mechanisms. Here, we show that IFN α induces retention of viral particles on the surface of fibroblasts, T cells, or primary lymphocytes infected with HIV-1 lacking the Vpu protein. Retained particles are tethered to cell surfaces, can be endocytosed, appear fully assembled, exhibit mature morphology, and can be detached by protease. Strikingly, expression of the HIV-1 Vpu protein attenuates the ability of human cells to adhere to, and thereby retain, nascent HIV-1 particles upon IFN α treatment. Vpu also counteracts the IFN α -induced retention of virus-like particles assembled from the Ebola virus matrix protein. Furthermore, levels of IFN α that suppress replication of Vpu-defective HIV-1 have little effect on wild-type HIV-1. Thus, we propose that HIV-1 expresses Vpu to counteract an IFN α -induced, general host defense that inhibits dissemination of enveloped virions from the surface of infected cells. of plasmid complexed with polyethylenimine. To generate
Mu Opioid Receptor Regulation of Gonadotropin-Releasing Hormone-Luteinizing Hormone Axis during Short-Term Food Deprivation: Role of Alpha 1 -Adrenoreceptor Signaling

Brain bio-energetic stability is required for optimal gonadal steroid positive-feedback activation of the gonadotropin-releasing hormone-I (GnRH-I)-pituitary luteinizing hormone (LH) neuroendocrine axis. Caudal hindbrain metabolic-sensory noradrenergic neurons counter energy deficiency by curtailing the mid-cycle LH surge. Central mu opioid receptors (mu-R) impose inhibitory effects of diverse physiological stimuli, including stress, on LH. To address the premise that mu-R attenuate the LH surge due to metabolic stress of food deprivation (FD), this study examined impacts of lateral ventricular administration of the selective mu-R antagonist CTOP on FD-associated patterns of GnRH-I protein expression and LH release in estradiol-primed ovariectomized female rats. FD caused CTOP-reversible reductions in circulating LH and in micropunch-dissected neural tissue GnRH-I and upstream neurotransmitter (kisspeptin)/ biosynthetic enzyme (neuronal nitric oxide synthase) protein content. FD up-regulated mu-R protein expression in reproduction-relevant preoptic structures, e.g. anteroventral periventricular (AVPV) and medial preoptic (MPN) nuclei, responses that were abolished by the alpha 1 adrenergic receptor ( α 1 A-R) inverse agonist prazosin. Current data implicate mu-R in FD attenuation of the E positive-feedback – induced LH surge. Results imply that FD-triggered noradrenergic input to the GnRH-I/LH axis acts in part to enhance reproductive neuroendocrine sensitivity to mu-R inhibition. Further studies are needed to characterize the neurochemical phenotype of AVPV and MPN neurons that express α 1 A- and/or mu-R, and to determine how these cells are organized within regulatory pathways to impose FD restraint of GnRH-1. in part, by augmentation of mu-R inhibition of upstream AVPV and MPN neurons. Results support the view that endophinergic action during FD down-regulates key stimulatory neurochemical cues to GnRH-I neurons, namely NO and kisspeptin. Ongoing studies aim to identify AVPV and MPN neurons that express α 1 A- and/or mu-R by neurotransmitter phenotype, and to determine how these cells are organized within regulatory pathways to impose FD restraint of GnRH-1.
(cid:2) -Secretase ADAM10 as Well as (cid:2) APPs Is Reduced in Platelets and CSF of Alzheimer Disease Patients

Background: Members of membrane-bound disintegrin metalloproteinases (ADAMs) were shown to be capable of cleaving amyloid precursor protein (APP) at the (cid:2) cleavage site in different cell systems. One of the candi- date (cid:2) -secretases identiﬁed in this family is ADAM10. The present study addresses the following major ques- tions: 1) Are the levels of an (cid:2) -secretase candidate (i.e., ADAM10) reduced in accessible cells of Alzheimer Dis- ease (AD) patients? 2) Are ADAM10 levels in the peripheral cells of AD patients related to a concomitant de- crease in (cid:2) APPs? Materials and Methods: Western Blot analysis of ADAM10 is performed on platelet homogenates from 33 sporadic AD patients and on 26 age-matched control sub- jects. Moreover, the levels of (cid:2) -secretase metabolite ( (cid:2) APPs) are tested both in platelets and cerebrospinal ﬂuid (CSF) of the same pool of subjects by means of West- ern blot with a speciﬁc antibody. Results: A signiﬁcant decrease of platelet ADAM10 levels is observed in patients affected by probable AD when compared to control subjects and this is paralleled by a re- duced level of (cid:2) APPs released from platelets. Moreover, in the same pool of AD patients, (cid:2) APPs levels were reduced concomitantly in CSF. Conclusions: ADAM10 is expressed in platelets. A reduced level of ADAM10 is observed in platelets obtained from AD patients compared to age-matched controls. Further, in the same pool of AD patients, a qualitatively and quantitatively similar decrease in (cid:2) APPs is present both in thrombin-activated platelets and CSF, thus suggesting that alterations of APP processing might occur both in the neuronal compartment and peripheral cells.
Predictive Value of Plasma Fibrinogen Levels in Patients Admitted for Acute Coronary Syndrome inflam-ClinicalInvestigation

In recent years, researchers have investigated the relationship between biological markers of inflammation and prognosis in patients who experience acute coronary syndromes; however, the association between plasma fibrinogen and coronary heart disease is still not clear. We studied the prognostic value of fibrinogen, an acute-phase protein that is directly involved in thrombotic processes, by measuring plasma fibrinogen levels serially in 136 patients who had acute coronary syndromes, 142 patients who had stable coronary heart disease, and 82 healthy control participants. Plasma fibrinogen levels were significantly higher in the patients with acute coronary syndromes (302 ± 90 mg/dL) than in the patients with stable coronary heart disease (274 ± 61 mg/dL) and the control group (243 ± 55 mg/dL) (both P <0.05). We also found significantly higher plasma fibrinogen levels in patients who developed clinical events than in those who did not, at 30 days and 2 years ( P <0.05). Cox regression analysis showed that high C- reactive protein values and plasma fibrinogen levels ≥ 350 mg/dL were predictors of poor long-term prognosis. The adjusted odds ratio (95% confidence interval) for patients who had higher levels of plasma fibrinogen was 5.207. Plasma fibrinogen level can be used as an independent predictor of major adverse cardiac events during short- and long-term follow-up ( P <0.01). The association is independent of other classical risk factors, such as age and sex. (Tex Heart Inst J 2010;37(2):178-83)
Drain Side N+ Layout Manners ("npnpn" Arranged-Type) on ESD Robustness in the 60-V pLDMOS-SCR

Electrostatic-discharge (ESD) immunity measurements of different layout manners in the drain-side of HV pLDMOS devices are investigated in this paper. Here, eleven kinds of drain-side "npnpn" arranged-types of pLDMOS-SCR parasitic structure are used to evaluate the layout impacts on ESD robustness. In this study, at first the layout type of N+ region is continuous extended into the drain-side P+ cathode. Secondly, the layout type of N+ region is modulated by some discrete-distributed areas in the drain-side. From the experimental results, we can find that the ESD capability of the continuous extended and discrete distributed in the drain-side can be promoted, where all of the secondary breakdown current (It2) values can be achieved 7 A. However, the discrete-distributed layout type has higher breakdown voltage (VBK) than that of the reference group (the pure none modulated pLDMOS-SCR npnpn-type structure). Therefore, the discrete-distributed layout types show good electrical properties and reliability immunities.
Effect of Vitamin A Deficiency in Dysregulating Immune Responses to Influenza Virus and Increasing Mortality Rates After Bacterial Coinfections

Background: Secondary bacterial coinfections are ranked as a leading cause of hospitalization and morbid conditions associated with influenza. Because vitamin A deficiency (VAD) and insufficiency are frequent in both developed and developing countries, we asked how VAD influences coinfection severity. Methods: VAD and control mice were infected with influenza virus for evaluation of inflammatory cytokines, cellular immune responses, and viral clearance. Influenza-infected mice were coinfected with Streptococcus pneumoniae to study weight loss and survival. Results: Naive VAD mouse lungs exhibited dysregulated immune function. Neutrophils were enhanced in frequency and there was a significant reduction in RANTES (regulated on activation of normal T cells expressed and secreted), a chemokine instrumental in T-cell homing and recruitment. After influenza virus infection, VAD mice experienced failures in CD4 + T-cell recruitment and B-cell organization into lymphoid structures in the lung. VAD mice exhibited higher viral titers than controls and slow viral clearance. There were elevated levels of inflammatory cytokines and innate cell subsets in the lungs. However, arginase, a marker of alternatively activated M2 macrophages, was rare. When influenza-infected VAD animals were exposed to bacteria, they experienced a 100% mortality rate. Conclusion: Data showed that VAD dysregulated the immune response. Consequently, secondary bacterial infections were 100% lethal in influenza-infected VAD mice.
Natural history of Huntington’s disease: evolution of modeling onset

Huntington’s disease (HD) is a unique disease caused by a CAG trinucleotide expansion in the Huntingtin gene and with the power to predict age-at-onset from subject-specific features like motor and neuroimaging measures. In clinical trials, properly modeling onset age is important because it improves power calculations and directs clinicians to recruit subjects with certain features. We discuss the history of modeling onset, from simple linear and logistic regression to advanced survival models. We highlight their advantages and disadvantages, emphasizing the methodological challenges when genetic mutation status is unavailable. We also discuss the potential bias and higher variability incurred from the uncertainty associated with subjective definitions for onset. Methods to adjust for the uncertainty in survival models are still in its infancy, but would be beneficial for HD and neurodegenerative diseases with long prodromal periods like Alzheimer’s and Parkinson’s disease.
meeting Mont Sainte-Odile: a sanctuary for GPCRs Conference on Signal Transduction of G-Protein-Coupled Receptors

and vertebrates). More than 1,000 GPCRs have been identified in vertebrates, and they have been classified into three main families according to their sequence homology and structural features. Family 1 is the largest, and its members have a short amino-terminal extracellular domain. This family includes a receptor for light (rhodopsin) and receptors that are activated by small ligands such as catecholamines and short peptides. Members of family 2 share a longer extracellular domain and are activated by large peptides such as glucagon and secretin. Members of family 3 include the metabotropic glutamate receptors (mGluRs) and γ -aminobutyric acid B (GABA B ) receptors and have large extracellular segments that fold into ligand-binding domains. The name GPCR derives from the ability of these proteins to recruit and regulate the activity of intracellular heterotrimeric G proteins. The activation of G proteins by the receptor facilitates GDP–GTP exchange on the G α -subunit. This is followed by the dis-sociation of the heterotrimeric complex into the GTP-bound G α -sub-unit and the G βγ -dimer. Both the G α -subunit and the G βγ -dimer activate or inhibit an ever-expanding list of effectors, including adenylyl cyclases, phopholipases and ion channels. On the basis of sequence similarities in their G α -subunits, G proteins have been grouped into four subfamilies: G s , G i/o , G q and G 12 . Whereas stimulatory (G s ) and inhibitory (G i/o ) G proteins are implicated in the regulation of adenylyl cyclase in the monastery where St Odile lived and died. This was a perfect place to shed new light on many questions concerning GPCR signalling and function. (Shown is a detail of the mosaic from the Chapel of Angels, Mont Sainte-Odile, Alsace, France. Modified by M. Passama.) aetiology of
Immersive virtual reality mirror therapy for upper limb recovery following stroke: A pilot study

Objective: This study was designed to examine the feasibility of immersive virtual reality (VR) mirror therapy for upper limb paresis after stroke using a head-mounted display, and provide preliminary evidence of efficacy. Design: Ten outpatients with chronic stroke, upper limb hemiparesis, and a low predisposition for motion sickness completed a 12-session program of 30 minutes each of immersive VR mirror therapy. The VR system provided the illusion of movement in the hemiparetic upper limb while suppressing the visual representation of the non-paretic side. Feasibility was assessed via patient compliance, adverse event tracking, the System Usability Scale, and the Simulator Sickness Questionnaire. Preliminary efficacy was evaluated using the Fugl-Meyer Upper Extremity (FM-UE) and Action Research Arm Test. Results: Immersive VR mirror therapy for patients with chronic stroke was safe, well-tolerated, and without adverse events, such as simulator sickness. Motor outcomes revealed a small improvement for the FM-UE from 21.7 (SD= 8.68) to 22.8 (SD= 9.19) that did not achieve statistical significance (p=0.084). Conclusion: Four weeks of immersive virtual reality mirror therapy was well-tolerated by chronic stroke patients. Our findings support further clinical trials of immersive VR technologies and visually-enhanced mirror therapies for stroke survivors.
Receiver domains control the active state stoichiometry of Aquifex aeolicus σ 54 activator NtrC4, as revealed by electrospray mass spectrometry

A common challenge with studies of proteins in vitro is determining which constructs and conditions are most physiologically relevant. σ 54 activators are proteins that undergo regulated assembly to form an active ATPase ring that enables transcription by σ 54 -polymerase. Previous studies of the AAA+ ATPase domains from σ 54 activators have shown that some are heptamers, while others are hexamers. Because the active oligomers assemble from off-state dimers, it was thought that even-numbered oligomers should dominate, and that heptamer formation might occur when individual domains of the activators were studied rather than the intact proteins. Here we present results from electrospray mass spectrometry experiments that characterize the assembly states of intact NtrC4 (a σ 54 activator from Aquifex aeolicus , an extreme thermophile) as well as its ATPase domain alone, and regulatory-ATPase and ATPase-DNA binding domain combinations. We show that the full-length and activated regulatory-ATPase proteins form hexamers, whereas the isolated ATPase domain, unactivated regulatory-ATPase and ATPase-DNA binding domain form heptamers. Activation of the N-terminal regulatory domain is the key factor stabilizing the hexamer form of the ATPase, relative to the heptamer.
Preparation of a novel ﬂoating ring capsule-type dosage form for stomach speciﬁc delivery

Study objectives were to develop a unique ﬂoating ring capsule dosage form which combines gastric soluble and insoluble portions, and to evaluate its suitability for stomach speciﬁc drug delivery. New ﬂoating ring capsules were developed using different polymers and were compared for various parameters. The formulation with HPMC and sodium CMC has better ﬂoating properties. The effects of polymers concentration on drug release were studies by in vitro release studies. The interaction studies of combined drug with polymers were determined using FT-IR spectroscopy. The entrapped air within the gel barrier and lower densities of HPMC and sodium CMC resulted in better ﬂoating behavior. Steady slow gel formations showed prolonged drug release. The in vitro release rates were generally found to be faster with low concentration of carbopol showing release within 2 h, while formulations containing high amount of HPMC showed release in 8 h. In particular, the higher concentration of HPMC formulation shows the best drug release performance. A very low change in peak shift was observed only with sodium alginate formulations. Further, FT-IR measurements conﬁrmed the absence of any chemical interactions. Results indicate that new ﬂoating ring capsule is a promise dosage form for stomach speciﬁc delivery.
summarizer browser extensions for PubMed Central

Summary: Figures in biomedical articles present visual evidence for research facts and help readers understand the article better. However, when figures are taken out of context, it is difficult to understand their content. We developed a summarization algorithm to summarize the content of figures and used it in our figure search engine (http://figuresearch.askhermes.org/). In this article, we report on the development of web browser extensions for Mozilla Firefox, Google Chrome and Apple Safari to display summaries for figures in PubMed Central and NCBI Images. Availability: The extensions can be downloaded from http:// figuresearch.askhermes. org/articlesearch/extensions.php. Contact: agarwal@uwm.edu Received on January 12, 2011; revised on March 1, 2011; accepted
Analgesic potential of PF-06372865, an a 2/ a 3/ a 5 subtype-selective GABA A partial agonist, in humans

Background: This study investigated the analgesic effects of two doses (15 and 65 mg) of PF-06372865, a novel a 2/ a 3/ a 5 gamma-aminobutyric acid A (GABA A ) subunit selective partial positive allosteric modulator (PAM), compared with placebo and pregabalin (300 mg) as a positive control. Methods: We performed a randomised placebo-controlled crossover study (NCT02238717) in 20 healthy subjects, using a battery of pain tasks (electrical, pressure, heat, cold and inﬂammatory pain, including a paradigm of conditioned pain modulation). Pharmacodynamic measurements were performed at baseline and up to 10h after dose. Results: A dose of 15 mg PF-06372865 increased pain tolerance thresholds (PTTs) for pressure pain at a ratio of 1.11 (90% conﬁdence interval [CI]: 1.02, 1.22) compared with placebo. A dose of 65 mg PF-06372865 led to an increase in PTT for the cold pressor at a ratio of 1.17 (90% CI: 1.03, 1.32), and pressure pain task: 1.11 (90% CI: 1.01, 1.21). Pregabalin showed an increase in PTT for pressure pain at a ratio of 1.15 (95% CI: 1.06, 1.26) and cold pressor task: 1.31 (90% CI: 1.16, 1.48). Conclusion: We conclude that PF-06372865 has analgesic potential at doses that do not induce signiﬁcant sedation or other intolerable adverse events limiting its clinical use. In addition, the present study established the potential role for this battery of pain tasks as a tool in the development of analgesics with a novel mechanism of action, for the treatment of various pain states including neuropathic pain and to establish proof-of-concept.
Resume Surovulation chez la vache suite a l ' administration d ' une gonadotrophine serique de jument gestante : effets de la dose et de la # onadotrophine serique de l ' antiserum

The effects of pregnant mare serum gonadotrophin (PMSG) dose and PMSG antiserum on superovulation in crossbred beef cows were studied. In experiment I, three groups were treated with 1200, 2400 or 3600 IU ofPMSG and 48 h later with prostaglandin (PGF). The mean numbers of corpora lutea (CL), unovulated follicles, and total ova/embryos collected increased as the PMSG dose increased. The percent of fertilized ova and transferable embryos was lowest in the highest dose group (p<0.05). In experiment II, all cows received 2500 IU ofPMSG; groups 1 and 2 were treated with sheep anti-PMSG serum at 48 h or 60 h after PGF; group 3 cows were PMSGonly controls. The number of CL was lowest and the number of unovulated follicles highest in the PMSG-only group (p<0.05). The number of CL was higher in group 2 (anti-PMSG at 60 h) than in the control group, with the anti-PMSG at 48 h not different from the other groups. Numbers of total ova/embryos, fertilized ova, and transferable embryos were higher (p<0.05) in both antiserum-treated groups relative to the PMSG-only group. We conclude that superovulation of beef cows with PMSG and treatment with PMSG antiserum will induce a higher superovulatory response and will result in higher CL numbers and fewer unovulated follicles. Further, the variability in the superovulatory response to PMSG treatment was still evident when PMSG antiserum was administered. Reproductive Biology Research Unit, Department of Obstetrics and Gynecology, College of Medicine (Gonzalez, Murphy) and Department of Herd Medicine and Theriogenology, Western College of Veterinary Medicine (Wang, Carruthers, Mapletoft), University of Saskatchewan, Saskatoon, Saskatchewan S7N OWO. Present address of Dr. A. Gonzalez: Facultad de Agronomia, Universidad Autonoma de Tamaulipas, A.P. #184, Cd. Victoria, Tamaulipas, Mexico 87149. Reprint requests to Dr. R.J. Mapletoft. This research was supported by the Agricultural Development Fund of Saskatchewan and drugs were provided by SanofiCanada, Coopers Agropharm Inc., Syntex Inc., and The Upjohn Company. Dr. H. Wang was supported by a Government of Saskatchewan-Province of Jilin, Peoples's Republic of China joint agreement. Partial results of this research were presented at the 1987 International Embryo Transfer Society meeting.
Epidermal Growth Factor Receptor Exon 20 Mutation Increased in Post-Chemotherapy Patients with Non – Small Cell Lung Cancer Detected with Patients ’ Blood Samples 1

PURPOSE: Patients with non – small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) – mutations have excellent response to EGFR tyrosine kinase inhibitors (TKIs), and exon 20 mutation accounts for most of TKI drug resistance. Nested polymerase chain reaction (PCR) was used to detect EGFR exon 20 mutations of patients with NSCLC after chemotherapy. The same is being analyzed with patients ’ characteristics. METHODS: Peripheral blood samples were collected from 273 patients with NSCLC, including 143 with adenocarcinoma (ADC) and 130 with squamous cell carcinoma (SCC), after chemotherapy. DNA was extracted from whole blood for nested PCR amplification and purification. Sequencing was carried out in an automated 3730 sequencer, followed by analysis of EGFR exon 20 mutations from nested PCR products. RESULTS: The mutations of EGFR exon 20 were mainly point mutations in rs1050171 (c.2361A>G) and rs56183713 (c.2457G>A). The point mutation was 28.21%, 28.46%, and 27.97% in patients with NSCLC, ADC and SCC, respectively. Men had an equivalent mutation (27.18%) to women (30.77%). The mutation in smokers and nonsmokers was 27.68% and 29.17%, respectively. In unselected patients, there was no correlation between EGFR exon 20 mutations and patients ’ characteristics of age, gender, smoking history, histologic type, or tumor-node-metastasis (TNM) staging system. In subgroup analyses, the EGFR mutation of patients with SCC was correlated with TNM stage [ P = . 013; odds ratio = 1.758; 95% confidence interval (CI) = 1.125-2.747]. CONCLUSIONS: The data indicate that the chemotherapy may induce EGFR-TKI – resistant mutation in NSCLC cells and EGFR-TKI should be used in the early stage of NSCLC but not after chemotherapy.