Miracle-dz/UniFAR-FTUs huggingface dataset:
Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins

The release of enveloped viruses from infected cells often requires a virally encoded activity, termed a late-budding domain (L domain), encoded by essential PTAP, PPXY, or YPDL sequence motifs. PTAP-type L domains recruit one of three endosomal sorting complexes required for transport (ESCRT-I). However, subsequent events in viral budding are poorly defined, and neither YPDL nor PPXY-type L domains require ESCRT-I. Here, we show that ESCRT-I and other class E vacuolar protein sorting (VPS) factors are linked by a complex series of protein–protein interactions. In particular, interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX, a mammalian orthologue of the yeast class E VPS factor, Bro1. Expression of certain ESCRT-III components as fusion proteins induces a late budding defect that afflicts all three L-domain types, suggesting that ESCRT-III integrity is required in a general manner. Notably, the prototype YPDL-type L domain encoded by equine infectious anemia virus (EIAV) acts by recruiting AIP-1/ALIX and expression of a truncated form of AIP-1/ALIX or small interfering RNA-induced AIP-1/ALIX depletion specifically inhibits EIAV YPDL-type L-domain function. Overall, these findings indicate that L domains subvert a subset of class E VPS factors to mediate viral budding, some of which are required for each of the L-domain types, whereas others apparently act as adaptors to physically link specific L-domain types to the class E VPS machinery.
Poverty of Elderly People in EU25

Annex A: Auxiliary Tables of Section 4 47 Table A.1: Sensitivity of poverty risks to the inclusion of imputed rent in Denmark.47 Table A.2: Sensitivity of poverty risks to Before-Housing-Costs and After-Hosuing-Costs measure of income in the UK 47 Annex B: Auxiliary Tables of Section 5 48 Table B.1: Average income composition of elderly and working age persons 48 Table B.2: Population shares of the various income groups, by age groups 50 Table B.3: Income composition of elderly and working age persons, by income groups 52 Table B.4: Average income composition of elderly and working age persons, by at-risk-of-poverty status 55 Table B.5: Income composition of elderly persons, with a further breakdown of old-age benefits (Using LIS data) 58 Table B.6: Personal income levels by income and age groups of elderly and working age persons 59 Table B.7: Personal income levels by at-risk-of-poverty status and age groups 62
Biochemical Characterization of the Human Copper Transporter Ctr1*

The trace metal copper is an essential cofactor for a number of biological processes including mitochondrial oxidative phosphorylation, free radical detoxification, neurotransmitter synthesis and maturation, and iron metabolism. Consequently, copper transport at the cell surface and the delivery of copper to intracellular proteins are critical events in normal physiology. Little is known about the molecules and biochemical mechanisms responsible for copper uptake at the plasma membrane in mammals. Here, we demonstrate that human Ctr1 (hCtr1) is a component of the copper transport machinery at the plasma membrane. hCtr1 transports copper with high affinity in a time-dependent and saturable manner and is metal-specific. hCtr1-mediated 64Cu transport is an energy-independent process and is stimulated by extracellular acidic pH and high K+ concentrations. hCtr1 exists as a homomultimer at the plasma membrane in mammalian cells. This is the first report on the biochemical characterization of the human copper transporter hCtr1, which is important for understanding mechanisms for mammalian copper transport at the plasma membrane.
Recognition of the Tryptophan-based Endocytosis Signal in the Neonatal Fc Receptor by the μ Subunit of Adaptor Protein-2*

Endocytosis of membrane proteins is typically mediated by signals present in their cytoplasmic domains. These signals usually contain an essential tyrosine or pair of leucine residues. Both tyrosine- and dileucine-based endocytosis signals are recognized by the adaptor complex AP-2. The best understood of these interactions occurs between the tyrosine-based motif, YXXΦ, and the μ2 subunit of AP-2. We recently reported a tryptophan-based endocytosis signal, WLSL, contained within the cytoplasmic domain of the neonatal Fc receptor. This signal resembles YXXΦ. We have investigated the mechanism by which the tryptophan-based signal is recognized. Both interaction assays in vitro and endocytosis assays in vivo show that μ2 binds the tryptophan-based signal. Furthermore, the WLSL sequence binds the same site as YXXΦ. Unlike the WXXF motif, contained in stonin 2 and other endocytic proteins, WLSL does not bind the α subunit of AP-2. These observations reveal a functional similarity between the tryptophan-based endocytosis signal and the YXXΦ motif, and an unexpected versatility of μ2 function.
Analysis of Bcl-2 protein expression in choroidal melanomas

Background: Bcl-2 protooncogene alterations are involved in tumorigenesis and may have prognostic ramifications. Aims: To investigate normal ocular structures and choroidal melanoma for: (1) Bcl-2 protein expression (semiquantitative staining values: SI, staining intensity; PP, percentage of positive cells; and IRS, immunoreactivity score) and (2) any associations between the staining values and clinicopathological features in these lesions. Materials/Methods: Bcl-2 protein expression was analysed in 24 choroidal melanomas using immunoperoxidase staining methods. Results: Bcl-2 protein expression was seen in corneal epithelium, lens epithelium, the ciliary body, and retinal cells. In these structures, the mean (SEM) values were: 1.1 (0.1), 1.6 (0.3), 1.1 (0.1), and 2.3 (0.3), respectively, for SI; 1.6 (0.2), 1.7 (0.1), 1.7 (0.2), and 1.7 (0.2) for PP, respectively; and 1.9 (0.4), 2.7 (0.5), 1.9 (0.1), and 4.0 (0.8), respectively, for IRS. Based on Bcl-2 immunoreactivity, the lesions were divided into two groups. The first group comprised 12 tumours with Bcl-2 expression. Bcl-2 expression was significantly higher in this group compared with normal ocular structures (1.5 (0.1) v 2.8 (0.2), 1.7 (0.1) v 3.5 (0.1), and 2.6 (0.3) v 9.3 (0.9) for mean (SEM) SI, PP, and IRS scores, respectively; p = 0.00). The second group comprised 12 tumours lacking Bcl-2 protein expression. There was no significant correlation between Bcl-2 protein expression and most of the clinicopathological features of these lesions. Conclusions: Bcl-2 protein expression is altered in choroidal melanomas.
Elevation of oleate‐activated phospholipase D activity during thymic atrophy

Various phospholipases are thought to be associated with the in vitro apoptosis of thymocytes. In the present study, the in vivo phospholipase D (PLD) activity of rat thymus was studied after whole‐body X‐irradiation or injection of dexamethasone (DEX). Using exogenous [14C]dipalmitoyl phosphatidylcholine (PC) as the substrate, an elevation of oleate‐activated PLD activity was observed during thymic atrophy. The activity increases were sevenfold at 48 hr after 5‐Gy irradiation and fourfold at 72 hr after injection of 5 mg/kg DEX. The elevation of PLD activity appeared to parallel extensive thymus shrinkage. An increased level of thymic phosphatidic acid (PA), the presumed physiological product of PLD action on PC, was also detected. By comparing the acyl chains of PA with those of other phospholipids, PA appeared to originate from PC. To assess the role of PLD during thymic atrophy, thymocytes and stromal cells were isolated. Although thymocytes themselves exhibited significant PLD activation, the major elevation in PLD activity (greater than fourfold) was found in isolated stromal cells. PLD was also activated during in vitro phagocytosis of apoptotic thymocytes by the macrophage‐like cell line P388D1. This in vitro phagocytosis was significantly inhibited by PLD action blockers, such as 2,3‐diphosphoglycerate and 1‐butanol. These observations strongly suggest that the alteration of oleate‐activated PLD activity is part of an in vivo event in the progression of thymic atrophy, including phagocytic clearance of apoptotic thymocytes.
Human immunodeficiency virus type 1 integrase: effect on viral replication of mutations at highly conserved residues

Sequence comparisons of the integrase (IN) proteins from different retroviruses have identified several highly conserved residues. We have introduced mutations at 16 of these sites into the integrase gene of human immunodeficiency virus type 1 and analyzed the phenotypes of the resulting viruses. The viruses were all normal for p24 content and reverse transcriptase activity. In addition, all of the mutants could infect T-cell lines and undergo reverse transcription, as assessed by PCR analysis. Most of the mutant viruses also had normal Western blot (immunoblot) profiles, although three of the mutations resulted in reduced signals for IN relative to the wild type on the immunoblots and mutation of residue W235 completely abolished recognition of the protein by pooled sera from human immunodeficiency virus type 1-positive patients. Mutations that have previously been shown to abolish activity in in vitro studies produced noninfectious viruses. The substitution of W235 was notable in producing a noninfectious virus, despite previous reports of this residue being nonessential for IN activity in vitro (A.D. Leavitt, L. Shiue, and H.E. Varmus, J. Biol. Chem. 268:2113-2119, 1993). In addition, we have identified four highly conserved residues that can be mutated without any affect on viral replication in T-cell lines.
District Influence on Principals' Efficacy and Sensemaking in their School Improvement Efforts

Part of a larger study of high-performing districts in Ontario, this mixed method (qualitative and quantitative) study identified school district actions perceived by principals to help them make sense of their leadership work and contribute to their sense of efficacy in carrying out that work. Qualitative data included interviews with 23 principals, 10 senior district leaders, and 5 trustees in two high-performing districts in the province. Narrative analysis was used to analyze these data. Quantitative data were provided by the responses of 1,563 principals and 250 senior district leaders to two forms of a survey which included sub-sets of questions about variables of special interest to this study. Descriptive statistics were used to summarize the survey results. Interview results showed that in the two study districts, each of 12 district actions framing the study were perceived to influence principals’ efficacy or principals’ sensemaking or both. Of those 12 district actions, principals in one of the two study districts identified 8 of the 12 district actions as especially influential in helping them to make sense of their work and to develop their sense of efficacy for carrying out that work; 10 of the 12 district actions were identified by principals in the second study district. Four of the 12 district actions were common across the responses of principals in both study districts including: networking interactions among principals; job-embedded and regional professional development opportunities; support from superintendents with the writing of school improvement plans; and emphasis and support with data interpretation and use for decision making processes. Except for one of these four district actions (use of evidence for decision making), survey results pointed to the same sets of district actions as particularly influential to both principals’ efficacy and sensemaking. This research adds to the understanding of what districts do that helps their school leaders work more effectively. Implications are identified for the actions of district leaders and for future research. %%%%PhD
Histochemical study of acute and chronic intraperitoneal nicotine effects on several glycolytic and Krebs cycle dehydrogenase activities in the frontoparietal cortex and subcortical nuclei of the rat brain

The effects of nicotine on the activity of different dehydrogenases in frontoparietal regions and subcortical nuclei of the rat brain have been studied using histochemical methods. Nicotine sulphate was intraperitoneally administered in acute (4 mg/kg/day × 3 days) or chronic (ALZET osmotic pump providing 2 mg/kg/day × 15 days) doses. The enzymes analyzed were glyceraldehyde‐3‐phosphate, lactate, malate and succinate dehydrogenases (gly3PDH, LDH, MDH, and SDH, respectively). The results demonstrate that chronic as well as acute administration of nicotine produced strong increases in all these enzymatic activities in the superior layers (I, II and III) of the frontoparietal cortex (cingulate, motor and somatosensory regions); but high increases were not seen in the deeper layers of the cortex or in the subcortical nuclei (substantia nigra, caudate‐putamen, nucleus accumbens or nucleus basalis magnocellularis). These hyperactivities were produced in brain regions with normally low enzymatic activity (cortex), but not in those with great intensity (subcortical nuclei). The results are in rough agreement with previous reports on nicotine‐induced increases in glucose utilization, gly3PDH genic expression and neuronal hyperactivity in the brain cortex; but significant discrepancies between the cortical enzymatic maps and those obtained both in these studies and others on nicotine(N)‐receptor localization have been appreciated. The results support the hypothesis that nicotinic cholinergic drugs can have metabolic, long‐lasting stimulant effects on cortical neurons at specific points (probably layer III pyramidal cells and structures with α7‐N‐receptors) of the cortical circuits that could be of great interest in improving altered cognitive functions that are present in Alzheimer disease, as well as in other less severe mental disturbances. Mitochondrial hyperfunction should also be evaluated as a possible side‐effect (as an oxidative stress inductor) of these kinds of drugs. J. Neurosci. Res. 64:626–635, 2001. © 2001 Wiley‐Liss, Inc.
The Effect of Crude Oil Price Moments on Socially Responsible Firms in Eurozone

The present study examines the effect of moments of crude oil prices including the variance, skewness and kurtosis, on the returns of the Dow Jones Sustainability Index (DJSI) of the Eurozone. The GARCH model is employed to examine the relationship of these moments with the DJSI of the Eurozone, for the time period from November 2001 until March 2015. According to our findings, an increase in the oil returns, as well as in the oil price volatility, leads to a decrease in the value of the Index employed. It was also found that asymmetry affects positively the stock price of the Eurozone social responsibility companies, because the more the asymmetry increases, the less the concentration of the prices to the right side of the distribution, consequently the more the investors feel that the related risk is reduced, as the frequency of oil prices is below the average oil price. On the contrary, it was found that the interaction of asymmetry and kurtosis of oil prices affect negatively the DJSI of the Eurozone, a fact that is attributed to the kind of the oil price distribution for the above mentioned time period
Temporal and spatial changes of quinolinic acid immunoreactivity in the immune system of lipopolysaccharide‐stimulated mice

Quinolinic acid (Quin), a metabolite of tryptophan, is a neurotoxin that has been implicated in a variety of neuropathologic disorders that have immune components. The goal of this study was to characterize the changes in the cellular localization of Quin immunoreactivity in a paradigm of immune stimulation with lipopolysaccharide (LPS) in vivo to provide a basis for further studies on the physiological role of Quin in the immune system. Intraperitoneal LPS injection significantly increased Quin immunoreactivity (IR) in lymphoid tissues within 24 h. Spatial changes in splenic Quin‐IR demonstrated a shift from the periarterial lymphoid sheaths to the follicles before returning to control levels by 72 h post‐LPS. The strongly Quin‐IR cells were tentatively identified as interdigitating dendritic cells and macrophages. Only minimal Quin‐IR was detected in liver and lung, even under conditions of LPS stimulation combined with tryptophan loading. These data emphasize the temporally and spatially specific nature of Quin‐IR changes in lymphoid tissues under conditions of immune stimulation and raise the possibility that Quin may have an immunomodulatory function. J. Leukoc. Biol. 57: 199–206; 1995.
A PCR‐based strategy to generate yeast strains expressing endogenous levels of amino‐terminal epitope‐tagged proteins

An epitope tag introduced to a gene of interest (GOI) greatly increases the ease of studying cellular proteins. Rapid PCR‐based strategies for epitope tagging a protein's C‐terminus at its native gene locus are widely used in yeast. C‐terminal epitope tagging is not suitable for all proteins, however. Epitope tags fused to the C‐terminus can interfere with function of some proteins or can even be removed by C‐terminal protein processing. To overcome such problems, proteins can be tagged with epitopes at their amino‐termini, but generating yeast strains expressing N‐terminal epitope tagged genes under control of the endogenous promoter at the native locus is comparatively more difficult. Strategies to introduce N‐terminal epitope tags have been reported previously but often introduce additional sequences other than the epitope tag into the genome. Furthermore, N‐terminal tagging of essential genes by current methods requires formation of diploid strains followed by tetrad dissection or expression of an additional copy of the GOI from a plasmid. The strategies described here provide a quick, facile means of epitope tagging the N‐terminus of both essential and nonessential genes in a two‐step PCR‐based procedure. The procedure has the significant advantage of leaving tagged genes under the control of their endogenous promoters, and no additional sequences other than the epitope tag encoding nucleotides are inserted into the genome.
Advances in antiplatelet technologies to improve cardiovascular disease morbidity and mortality: a review of ticagrelor

Antiplatelet therapy is widely used with proven benefit for the prevention of further ischemic cardiac complications in patients with acute coronary syndrome. Treatment guidelines for acute coronary syndrome and percutaneous coronary intervention now recommend the use of oral antiplatelet agents including ticagrelor, prasugrel, or clopidogrel in combination with aspirin to comprise dual antiplatelet therapy for the prevention of recurrent ischemic events. The limitations of conventional antiplatelet therapy with clopidogrel or prasugrel include the potential for low response to clopidogrel identified through platelet reactivity or genetic testing, increased risk of bleeding with prasugrel, or slower return to normal platelet activity in patients who received either prasugrel or clopidogrel prior to emergent or planned surgical procedures. This review will discuss the pharmacokinetic and pharmacodynamic properties of ticagrelor in comparison to conventional P2Y12 receptor inhibitors and its utility in patients identified as low responders to clopidogrel. Completed clinical studies and substudies comparing ticagrelor to clopidogrel and ongoing clinical trials evaluating ticagrelor in acute coronary syndrome patients will also be reviewed.
More awakenings and heart rate variability during supine sleep in preterm infants.

OBJECTIVE The Task Force of The American Academy of Pediatrics (1996) recommends the nonprone sleeping position for asymptomatic preterm infants to prevent sudden infant death syndrome. The mechanism by which the nonprone sleeping position reduces the rate of sudden infant death syndrome is unclear for full-term infants and the precise effect of sleeping position on sleep and cardiorespiratory characteristics has never been addressed in preterm infants. The purpose of the present study was to clarify the effect of sleeping position on sleep and cardiorespiratory characteristics in preterm infants at an age when they are ready for discharge. STUDY DESIGN Sixteen asymptomatic preterm infants were studied in both supine and prone sleeping positions at 36.5 +/- 0.6 weeks' postconceptional age using videosomnography. Sleep, respiratory, and heart rate characteristics were compared between the two positions using each infant as his/her own control. RESULTS More awakenings (ie, arousals >/=60 seconds) were seen during all sleep states in the supine sleeping position but overall the total sleep and percent sleep state were not affected by sleeping position. After each feeding, the first quiet sleep was significantly shorter, with more heart rate variability and awakenings in the supine position. There were no significant differences in the occurrence of arousals (<60 seconds) or the incidence or severity of apnea and periodic breathing. No clinically significant apnea (>/=15 seconds), bradycardia, or oxygen desaturations were seen. CONCLUSION In 36-week-postconceptional age preterm infants, the supine sleeping position had less quiet sleep and was associated with greater heart rate variability during the first sleep cycle after the feeding. More awakenings were seen during all sleep states in the supine position. These data support the American Academy of Pediatrics recommendation for "Back to Sleep" for asymptomatic preterm infants because more awakenings and lower threshold for arousal may provide some benefit for the infant responding to a life-threatening event. However, further studies are needed to address positional effect on the physiologic measures in preterm infants at older ages (later stages of development). Precisely what constitutes the most healthy or advantageous sleep for newborn infants remains an important question.
Traditional Chinese medicine--women's experiences in the treatment of infertility.

BACKGROUND Infertility affects about 15% of couples. Many women proceed to reproductive clinics for in vitro fertilisation, with some exploring a range of alternative or complementary options. We explored women's experiences with traditional Chinese medicine (TCM) for the treatment of infertility. METHODS We interviewed 25 women with primary or secondary infertility, recurrent miscarriage or stillbirth who had consulted TCM practitioners. We explored women's experience of TCM and fertility clinics and analysed interviews thematically. RESULTS Women appreciated the noninvasive diagnostic techniques TCM practitioners used to identify 'imbalances' causing infertility, learnt how to assess fertility indicators, and valued the focused personal care provided. All noticed improved menstrual cycles. Women wished for integration of holistic therapies in infertility management. DISCUSSION Our study highlights the need for patient centred care and fertility education, and suggests that some women see a possible role for TCM as part of infertility management.