Miracle-dz/UniFAR-FTUs huggingface dataset:
The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences

We investigated whether genes escape X chromosome inactivation by positioning outside of the territory defined by XIST RNA. Results reveal an unanticipated higher order organization of genes and noncoding sequences. All 15 X-linked genes, regardless of activity, position on the border of the XIST RNA territory, which resides outside of the DAPI-dense Barr body. Although more strictly delineated on the inactive X chromosome (Xi), all genes localized predominantly to the outer rim of the Xi and active X chromosome. This outer rim is decorated only by X chromosome DNA paints and is excluded from both the XIST RNA and dense DAPI staining. The only DNA found well within the Barr body and XIST RNA territory was centromeric and Cot-1 DNA; hence, the core of the X chromosome essentially excludes genes and is composed primarily of noncoding repeat-rich DNA. Moreover, we show that this core of repetitive sequences is expressed throughout the nucleus yet is silenced throughout Xi, providing direct evidence for chromosome-wide regulation of “junk” DNA transcription. Collective results suggest that the Barr body, long presumed to be the physical manifestation of silenced genes, is in fact composed of a core of silenced noncoding DNA. Instead of acting at a local gene level, XIST RNA appears to interact with and silence core architectural elements to effectively condense and shut down the Xi.
A plea for more interactions between psycholinguistics and natural language processing research

A new development in psycholinguistics is the use of regression analyses on tens of thousands of words, known as the megastudy approach. This development has led to the collection of processing times and subjective ratings (of age of acquisition, concreteness, valence, and arousal) for most of the existing words in English and Dutch. In addition, a crowdsourcing study in the Dutch language has resulted in information about how well 52,000 lemmas are known. This information is likely to be of interest to NLP researchers and computational linguists. At the same time, large-scale measures of word characteristics developed in the latter traditions are likely to be pivotal in bringing the megastudy approach to the next level.
Chronic exposure to alcohol during development alters the responses to excitatory amino acids in cultured Purkinje neurons.

The effects of chronic alcohol exposure during development on the responses evoked by glutamate and the selective excitatory amino acid receptor agonists quisqualate (Quis) and kainate were studied in cultured cerebellar Purkinje neurons. The cultures were treated with 22 mM or 44 mM ethanol continuously for one or two weeks during the main period of morphological and physiological development. Extracellular recordings used for most studies characterized the responses to all 3 agonists as initial increase in simple spike firing, usually including a period of burst activity, followed by reduced activity or total inhibition, then return to control firing pattern. Analysis of these responses and background spontaneous activity showed several significant differences between control and ethanol treated Purkinje neurons. Background spontaneous firing, agonist evoked firing, the initial period of activity of the response to Quis, and the inhibitory period of the response to glutamate were all significantly reduced in the chronically treated neurons; the inhibitory period of the response to kainate was significantly increased. In contrast to the effects of chronic ethanol exposure, acutely administered ethanol significantly increased background spontaneous firing and the inhibitory period of the response to Quis. Thus, administering both acute and chronic ethanol altered the responses evoked by excitatory amino acids in the developing Purkinje neurons. The effect of chronic ethanol exposure on some response components was similar for all agonists tested and may be linked to changes in intrinsic membrane properties. However, alterations in the inhibitory component of the agonist responses were agonist specific, indicating that receptor-linked actions of ethanol were involved. (ABSTRACT TRUNCATED AT 250 WORDS)
A Multi-agent Tool to Annotate Biological Sequences

Nowadays, great challenges are imposed by the existence of enormous volume of DNA and RNA sequences, which are continuously being discovered by genome sequencing projects, through the automatic sequencers based on massively parallel sequencing technologies. Thus, the task of identifying biological function for these sequences is a key activity in these high-throuput sequencing projects, where the automatic annotation must be significantly improved. In this context, this paper presents a multi-agent approach to address the important issue of automatic annotation in genome projects. We developed a sophisticated prototype named BioAgents, which simulates biologists knowledge and experience to annotate DNA or RNA sequences in genome sequencing projects, where different specialized intelligent agents work together to accomplish the
Human apolipoprotein A-IV. Intestinal origin and distribution in plasma.

The role of the human intestine has been explored as a site of synthesis of apoA-IV, a major apoprotein of human intestinal triglyceride-rich lipoproteins. Intestinal biopsies were performed on normal volunteers while fasting and after lipid ingestion. Indirect immunofluorescence demonstrated a marked increase in immunofluorescence for apoA-IV during lipid absorption consistent with an increased intracellular content. ApoA-IV comprised 10-13% of chylomicron apoprotein and 24-30% of intestinal very low density lipoprotein (VLDL) as assessed by densitometry of sodium dodecyl sulfate gels of lipoproteins from chylous urine (mesenteric lymphatic-urinary fistula) and thoracic duct lymph (postoperative fistula). After one subject with chyluria ingested 40 g of corn oil, triglyceride excretion in urine was accompanied by an increased excretion of apoA-IV. 11.5 g of triglyceride and 81 mg of apoA-IV were recovered in the urine. In chylous urine 56% of apoA-IV was in the triglyceride-rich lipoproteins (chylomicrons and intestinal VLDL) and 44% in the d > 1.006-g/ml fraction. Normal plasma apoA-IV was 15.7+/-0.9 mg/dl (n = 14) whereas four subjects with abetalipoproteinemia had reduced levels 1.2, 7.6, 9.6, and 8.3 mg/dl, respectively. Lipid feeding in normal volunteers resulted in a rise in plasma apoA-IV (16.1+/-0.7 mg/dl to 18.5+/-0.7 mg/dl, n = 5, P < 0.01). In fasting plasma, 98% of apoA-IV was in the d > 1.21-g/ml fraction. In lipemic plasma, 10% of apoA-IV was associated with triglyceride-rich lipoproteins and 90% with the d > 1.21-g/ml fraction. Agarose column chromatography of fasting plasma confirmed that the bulk of plasma apoA-IV is free, unassociated with lipoproteins. These results demonstrate that apoA-IV is present in human intestinal epithelial cells and is secreted as a chylomicron and VLDL apoprotein. Within fasting plasma most of the apoA-IV is found free, unassociated with lipoproteins. After lipid ingestion apoA-IV is also found in plasma chylomicrons indicating that some apoA-IV remains associated with chylomicrons in plasma during chylomicron metabolism, although some may be transferred from the chylomicron surface.
Effects of tumour necrosis factor-alpha and inhibition of protein kinase C on glucose uptake in L6 myoblasts.

Clinical and experimental studies have implicated high circulating levels of the cytokine tumour necrosis factor-alpha (TNF-alpha) in the pathogenesis of insulin resistance, not only in obesity and diabetes, but also in clinical conditions associated with cachexia and sepsis. TNF-alpha impairs insulin-mediated glucose uptake in adipocytes, but because of lipolytic effects the interpretation of clinical studies and the extent to which TNF-alpha affects muscle insulin sensitivity are unclear. In addition, protein kinase C (PKC) has recently been implicated in the mechanism of TNF-alpha-induced insulin resistance. The present study investigated the effects of TNF-alpha and a PKC inhibitor (RO-318220) on basal and insulin-stimulated 2-[(3)H]deoxyglucose uptake in cultured L6 myoblasts. Reverse transcriptase-PCR analysis confirmed that L6 myoblasts express TNF-alpha receptors I and II (p60 and p80). Dose-response curves for glucose uptake were fitted to a quadratic function to derive C(I-150) values (concentration of insulin required to increase glucose uptake by 50%). Incubation with TNF-alpha at 1 or 10 ng/ml for 24 h had no significant effect on basal glucose uptake, insulin sensitivity or maximal insulin responsiveness. C(I-150) values (means+/-S.E.M.) were as follows: basal, 91.2+/-13 nM; 1 ng/ml TNF-alpha, 102+/-12 nM; and basal, 70.8+/-13 nM; 10 ng/ml TNF-alpha, 43.7+/-40 nM. PKC inhibition markedly attenuated glucose uptake, but there was no difference in insulin sensitivity with RO-318220 alone compared with RO-318220+TNF-alpha. In conclusion, although increased TNF-alpha expression and plasma concentrations have been implicated in the pathogenesis of insulin resistance in various clinical states, there is no evidence that TNF-alpha impairs insulin-stimulated glucose uptake in a skeletal-muscle-derived cell line.
Iowa State University From the SelectedWorks of Steven M . Lonergan 1995 A muscle hypertrophy condition in lamb ( callipyge ) : Characterization of effects on muscle growth and meat quality traits

The present experiment was conducted to determine the effect of the callipyge phenotype on traits affecting muscle growth and meat tenderness. Dorset wethers (n = 40) that were either carriers or non-carriers were fed grain and slaughtered at 169 d of age. Callipyge phenotype did not affect ( P > .05) slaughter weight, hot carcass weight, or weights of the heart, spleen, viscera, kidney-pelvic fat, head, and pelt; however, callipyge lambs had a higher dressing percentage and lighter lungs, liver, and kidneys ( P < .01). Callipyge lambs had reduced fat thickness and marbling score and higher leg scores and longissimus area (34%). Adductor (30%), biceps femoris (42%), gluteus group (31%), longissimus (32%), psoas group (20%), quadriceps femoris (18%), semimembranosus (38%), and semitendinosus (26%) weights were higher in the callipyge phenotype ( P < .01); however, phenotype did not affect ( P > .05) weights of infraspinatus or supraspinatus. Longissimus pH and temperature declines were not affected ( P > .05) by phenotype. Longissimus myofibril fragmentation index was lower at 1 (27%), 7 (35%), and 21 (37%) d postmortem and Warner-Bratzler shear force was higher at 1, 7, and 21 d postmortem in the callipyge phenotype ( P < .01). Shear force values of callipyge lambs at 21 d postmortem tended to be greater ( P = .12) than shear force values of non-carriers at 1 d postmortem. Activities of calpastatin (83%) and m-calpain (45%) were higher in the callipyge ( P < .01); however, mcalpain activity was not affected ( P > .05). Longissimus and semitendinosus RNA concentration, DNA content, RNA content, protein content, and the RNA: DNA ratio were higher ( P < .05), but DNA concentration, protein concentration, and protein:DNA were not affected in the callipyge phenotype. The higher calpastatin activity associated with callipyge suggests that protein degradation may be reduced in the live animal. Additionally, the increased muscle DNA content associated with the callipyge phenotype suggests an increase in satellite cell proliferation, and results in an increased capacity of skeletal muscle to accumulate and maintain myofibrillar protein. These results suggest that both reduced rate of protein degradation and higher capacity for protein synthesis are consequences of the callipyge condition.
The Probiotic Escherichia coli Nissle 1917 Reduces Pathogen Invasion and Modulates Cytokine Expression in Caco-2 Cells Infected with Crohn's Disease-Associated E. coli LF82

ABSTRACT Increased numbers of adherent invasive Escherichia coli (AIEC) have been found in Crohn's disease (CD) patients. In this report, we investigate the potential of the probiotic Escherichia coli Nissle 1917 (EcN) to reduce features associated with AIEC pathogenicity in an already established infection with AIEC reference strain LF82.
Clinical pharmacology and pharmacokinetics of antiretrovirals in Asia

Pharmacokinetics can be used to establish dose response relationships in terms of efficacy and toxicity. Nevertheless the majority of the registered dose in the treatment of HIV are based on data from Caucasian men. It is questionable however if the recommended doses are optimal for all ethnicities and in all circiumstances. Several studies suggest that a more population-based approach may benefit different ethnicities. Here we review the pharmacokinetics of commonly used non-nucleoside analog reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in the Asian setting, for both adults and children. Studies of nevirapine, efavirenz, saquinavir, lopinavir, ritonavir, indinavir and atazanavir have been reported mostly among Thai patients. The data strongly indicated that Thai and most likely Asians have on average a significantly higher exposure to both the drugs classes (NNRTIs and PIs) compared to the Caucasian. In patients with active tuberculosis who are taking rifampicin, the standard dose of either efavirenz or nevirapine was found to be sufficient and efficacious for Asians with average body weight of 60 kg. Lower dose studies of saquinavir, indinavir, lopinavir and atazanaivr have shown promising efficacy results, however most are small scale studies. In pregnancy, nevirapine seems an adequate option whereas efavirenz has no PK data during the third trimester. In conclusion, more likely Asians are significantly higher exposed to both NNRTIs and PIs compared to the Caucasians. Further studies on pharmacokinetics, TDM and larger scale clinical trials among Asian populations are warranted to identify suitable low doses of ARVs for mclusion in the clinical practice guidelines of this region.
Relationship between ultra-processed foods and metabolic syndrome in adolescents from a Brazilian Family Doctor Program

Abstract Objective To estimate the association between food intake and metabolic syndrome (MetS). Design Cross-sectional design conducted from July 2006 to December 2007. Setting Adolescents assisted by the Family Doctor Program (FDP) in Niterói, a metropolitan area in Rio de Janeiro State, Brazil. Subjects Survey of 210 adolescents. Individuals with three or more of the following components of MetS were classified as having this syndrome: TAG ≥ 110 mg/dl; HDL cholesterol < 50 mg/dl for girls aged 12–19 years and boys aged 12–14 years or <45 mg/dl for boys aged 15–19 years; waist circumference ≥75th percentile; serum glucose >100 mg/dl; and blood pressure ≥90th percentile. A semi-quantitative FFQ was used, and foods were grouped as: unprocessed or minimally processed foods (Group 1), processed culinary and food industry ingredients (Group 2) and ultra-processed foods (Group 3). The associations between food consumption and MetS were adjusted for sociodemographic, behavioural and family history covariates and were estimated using generalized estimation equations with the Poisson regression model. Results MetS was diagnosed in 6·7 % of the adolescents; the most frequent diagnostic criteria included the reduction of HDL cholesterol (46·7 %), elevated serum glucose (17·1 %) and the elevation of waist circumference (16·7 %). Crude analysis showed higher average daily intakes of energy, carbohydrates and ultra-processed foods among adolescents with MetS. After statistical adjustment, the intake of ultra-processed foods (≥3rd quartile) remained associated with MetS (prevalence ratio = 2·5; P = 0·012). Conclusions High consumption of ultra-processed foods was associated with the prevalence of MetS in this adolescents group.
Utilité des tests fonctionnels dans les neuropathies amyloïdes familiales

I.4 But du travail Un travail de these mene par une doctorante en physiopathologie (Irene Calero-Romero, sous la direction du Prof. F. Feihl, CHUV) a permis de recenser une quinzaine de patients souffrant de NAF (neuropathie amyloide familiale) et d'evaluer l'utilite de mesures de quantification par « laser-doppler flowmetry». Cette etude a investigue une technique basee sur le reflexe d'axone vasomoteur cutane, en estimant le flux sanguin cutane avant et apres l'application locale d'un stimulus electrique ou chimique (histamine), par les proprietes doppler d'un balayage laser de la peau. La fonction des PF peripheriques a pu etre ainsi objectivee en mesurant l'importance de l'erytheme induit. Dans ce contexte d'atteinte selective dans les NPF et de l'evaluation des PF par laser Doppler, ont ete aussi etudiees les correlations entre donnees cliniques et le testing sensitif cutane (QST). Les objectifs de ce travail de Maitrise ont donc ete de rassembler les dossiers des patients NAF en etudiant les donnees epidemiologiques, cliniques, biologiques et les examens complementaires, et de les correler aux deficits quantifies par le QST.
Low Effort Crowdsourcing: Leveraging Peripheral Attention for Crowd Work

Crowdsourcing systems leverage short bursts of focused attention from many contributors to achieve a goal. By requiring people’s full attention, existing crowdsourcing systems fail to leverage people’s cognitive surplus in the many settings for which they may be distracted, performing or waiting to perform another task, or barely paying attention. In this paper, we study opportunities for low-effort crowdsourcing that enable people to contribute to problem solving in such settings. We discuss the design space for low-effort crowdsourcing, and through a series of prototypes, demonstrate interaction techniques, mechanisms, and emerging principles for enabling low-effort crowdsourcing.
Studies on the pathogenesis of avascular retina and neovascularization into the vitreous in peripheral severe retinopathy of prematurity (an american ophthalmological society thesis).

PURPOSE To study vascular endothelial growth factor (VEGF) regulation in the development of intravitreous neovascularization and peripheral avascular retina in peripheral severe retinopathy of prematurity (ROP). METHODS The rat 50/10 model of ROP mimics zone II, stage 3 severe ROP and recreates fluctuations in transcutaneous oxygen levels in preterm infants. On postnatal (p) day ages p0, p8, p11-p14, and p18, retinas from the model or room-air (RA) age-matched pups were analyzed for mRNA of VEGF splice variants and receptors using real-time polymerase chain reaction or VEGF protein using enzyme-linked immunosorbent assay. RESULTS On p14, when retinas were only 70% vascularized in the model but fully vascularized in RA, VEGF₁₆₄ expression was threefold greater in the model compared to RA. On p18, intravitreous neovascularization was associated with a 5-fold increase in VEGF₁₆₄ mRNA in the model compared to RA. By analysis of variance, VEGF₁₆₄ and VEGFR2 mRNAs were up-regulated in association with increasing developmental age (P<.0001 for both comparisons) or exposure to the model compared to RA (P<.0001 and P=.0247, respectively), whereas increasing developmental age was associated only with up-regulated VEGF₁₂₀ (P=.0006), VEGF₁₈₈ (P=.0256), and VEGFR1 (P<.0001) mRNAs. VEGF protein increased significantly in the model and on p14 and p18 compared to RA (P<.0001). CONCLUSIONS The model mimics contemporary severe ROP in the United States unlike other models of oxygen-induced retinopathy. Compared to RA retinas, VEGF significantly increased in association with avascular retina and intravitreous neovascularization. A hypothesis is proposed that VEGF up-regulation plays a role in the development of both important features.
CapA, an Autotransporter Protein of Campylobacter jejuni, Mediates Association with Human Epithelial Cells and Colonization of the Chicken Gut

ABSTRACT Two putative autotransporter proteins, CapA and CapB, were identified in silico from the genome sequence of Campylobacter jejuni NCTC11168. The genes encoding each protein contain homopolymeric tracts, suggestive of phase variation mediated by a slipped-strand mispairing mechanism; in each case the gene sequence contained frameshifts at these positions. The C-terminal two-thirds of the two genes, as well as a portion of the predicted signal peptides, were identical; the remaining N-terminal portions were gene specific. Both genes were cloned and expressed; recombinant polypeptides were purified and used to raise rabbit polyclonal monospecific antisera. Using immunoblotting, expression of the ca.116-kDa CapA protein was demonstrated for in vitro-grown cells of strain NCTC11168, for 4 out of 11 recent human fecal isolates, and for 2 out of 8 sequence-typed strains examined. Expression of CapB was not detected for any of the strains tested. Surface localization of CapA was demonstrated by subcellular fractionation and immunogold electron microscopy. Export of CapA was inhibited by globomycin, reinforcing the bioinformatic prediction that the protein is a lipoprotein. A capA insertion mutant had a significantly reduced capacity for association with and invasion of Caco-2 cells and failed to colonize and persist in chickens, indicating that CapA plays a role in host association and colonization by Campylobacter. In view of this demonstrated role, we propose that CapA stands for Campylobacter adhesion protein A.
Angiotensinogen-Deficient Mice Exhibit Impairment of Diet-Induced Weight Gain with Alteration in Adipose Tissue Development and Increased Locomotor Activity.

White adipose tissue is known to contain the components of the renin-angiotensin system, which gives rise to angiotensin II from angiotensinogen (AGT). Recent evidence obtained in vitro and ex vivo is in favor of angiotensin II acting as a trophic factor of adipose tissue development. To determine whether AGT plays a role in vivo in this process, comparative studies were performed in AGT-deficient (agt−/−) mice and control wild-type mice. The results showed that agt−/− mice gain less weight than wild-type mice in response to a chow or high fat diet. Adipose tissue mass from weaning to adulthood appeared altered rather specifically, as both the size and the weight of other organs were almost unchanged. Food intake was similar for both genotypes, suggesting a decreased metabolic efficiency in agt−/− mice. Consistent with this hypothesis, cellularity measurement indicated hypotrophy of adipocytes in agt−/− mice with a parallel decrease in the fatty acid synthase activity. Moreover, AGT-deficient mice exhibit.
Changes in tactile stimuli‐induced behavior and c‐Fos expression in the superficial dorsal horn and in parabrachial nuclei after sciatic nerve crush

Neurons in the superficial laminae of the dorsal horn are dominated by input from peripheral nociceptors. Following peripheral nerve injury, low threshold mechanoreceptive Aβ‐fibers sprout from their normal termination site in laminae III/IV into laminae I–II and this structural reorganization may contribute to neuropathic tactile pain hypersensitivity. We have now investigated whether a sciatic nerve crush injury alters the behavioral response in rats to tactile stimuli and whether this is associated with a change in the pattern of c‐Fos expression in the dorsal horn and the parabrachial area of the brainstem. Sciatic nerve crush resulted in a patchy but marked tactile allodynia manifesting first at 3 weeks and persisting for up to 52 weeks. C‐Fos expression in the dorsal horn and parabrachial region was never observed on brushing the skin of the sciatic nerve territory in animals with intact nerves, but was found after sciatic nerve crush with peripheral regeneration. We conclude that after nerve injury, low threshold mechanoreceptor fibers may play a major role in producing pain‐related behavior by activating normally nociceptive‐specific regions of the central nervous system such as the superficial laminae of the dorsal horn and the parabrachial area. J. Comp. Neurol. 428:45–61, 2000. © 2000 Wiley‐Liss, Inc.