Miracle-dz/UniFAR-FTUs huggingface dataset:
Dietary choice affects Shiga toxin-producing Escherichia coli (STEC) O157:H7 colonization and disease

Significance We demonstrated that dietary fiber content affects susceptibility to Shiga toxin (Stx)-producing Escherichia coli (STEC) infection in mice. We showed that high fiber diet (HFD)-fed mice had elevated levels of butyrate, a beneficial gut metabolite that paradoxically enhances the cell-killing capacity of Stx. We also found that the amount of gut bacteria in HFD-fed mice increased whereas the percent of commensal Escherichia species (spp) decreased compared with animals fed a low fiber diet (LFD). These changes led to higher E. coli O157:H7 colonization levels, more weight loss, and greater rates of death in HFD-fed than in LFD-fed STEC-infected animals. The likelihood that a single individual infected with the Shiga toxin (Stx)-producing, food-borne pathogen Escherichia coli O157:H7 will develop a life-threatening sequela called the hemolytic uremic syndrome is unpredictable. We reasoned that conditions that enhance Stx binding and uptake within the gut after E. coli O157:H7 infection should result in greater disease severity. Because the receptor for Stx, globotriaosylceramide, is up-regulated in the presence of butyrate in vitro, we asked whether a high fiber diet (HFD) that reportedly enhances butyrate production by normal gut flora can influence the outcome of an E. coli O157 infection in mice. To address that question, groups of BALB/c mice were fed high (10%) or low (2%) fiber diets and infected with E. coli O157:H7 strain 86-24 (Stx2+). Mice fed an HFD exhibited a 10- to 100-fold increase in colonization, lost 15% more body weight, exhibited signs of morbidity, and had 25% greater mortality relative to the low fiber diet (LFD)-fed group. Additionally, sections of intestinal tissue from HFD-fed mice bound more Stx1 and expressed more globotriaosylceramide than did such sections from LFD-fed mice. Furthermore, the gut microbiota of HFD-fed mice compared with LFD-fed mice contained reduced levels of native Escherichia species, organisms that might protect the gut from colonization by incoming E. coli O157:H7. Taken together, these results suggest that susceptibility to infection and subsequent disease after ingestion of E. coli O157:H7 may depend, at least in part, on individual diet and/or the capacity of the commensal flora to produce butyrate.
Performance Analysis of Decode-and-Forward Relaying in Gamma-Gamma Fading Channels

We analyze performance of the decode-and-forward (DF) protocol in the free space optical (FSO) links following the Gamma-Gamma distribution. The cumulative distribution function (cdf) and probability density function (pdf) of a random variable containing mixture of the Gamma-Gamma and Gaussian random variables is derived. By using the derived cdf and pdf, average bit error rate of the DF relaying is obtained.
Effect of DA-9701 on Gastric Motor Function Assessed by Magnetic Resonance Imaging in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial

Background Improving gastric accommodation and gastric emptying is an attractive physiological treatment target in patients with functional dyspepsia (FD). We evaluated the effect of DA-9701, a new drug for FD, on gastric motor function after a meal in healthy volunteers using magnetic resonance imaging (MRI). Methods Forty healthy volunteers were randomly allocated to receive either DA-9701 or placebo. After 5 days of treatment, subjects underwent gastric MRI (60 min before and 15, 30, 45, 60, 90, and 120 min after a liquid test meal). Gastric volume was measured through 3-dimensional reconstruction from MRI data. We analyzed 4 outcome variables including changes in total gastric volume (TGV), proximal TGV, and proximal to distal TGV ratio after a meal and gastric emptying rates after adjusting values at the pre-test meal. Results Changes in TGV and proximal TGV after a meal did not differ between the DA-9701 and placebo groups (difference between groups -25.9 mL, 95% confidence interval [CI] -54.0 to 2.3 mL, P = 0.070 and -2.9 mL, 95% CI -30.3 to 24.5 mL, P = 0.832, respectively). However, pre-treatment with DA-9701 increased postprandial proximal to distal TGV ratio more than placebo (difference between groups 0.93, 95% CI 0.08 to 1.79, P = 0.034). In addition, pre-treatment with DA-9701 significantly increased gastric emptying as compared with placebo (mean difference between groups 3.41%, 95% CI 0.54% to 6.29%, P = 0.021, by mixed model for repeated measures). Conclusion Our results suggested that DA-9701 enhances gastric emptying and does not significantly affect gastric accommodation in healthy volunteers. Further studies to confirm whether DA-9701 enhances these gastric motor functions in patients with FD are warranted. Trial Registration ClinicalTrials.gov NCT02091635
Interplay between H1 and HMGN epigenetically regulates OLIG1&2 expression and oligodendrocyte differentiation

Abstract An interplay between the nucleosome binding proteins H1 and HMGN is known to affect chromatin dynamics, but the biological significance of this interplay is still not clear. We find that during embryonic stem cell differentiation loss of HMGNs leads to down regulation of genes involved in neural differentiation, and that the transcription factor OLIG2 is a central node in the affected pathway. Loss of HMGNs affects the expression of OLIG2 as well as that of OLIG1, two transcription factors that are crucial for oligodendrocyte lineage specification and nerve myelination. Loss of HMGNs increases the chromatin binding of histone H1, thereby recruiting the histone methyltransferase EZH2 and elevating H3K27me3 levels, thus conferring a repressive epigenetic signature at Olig1&2 sites. Embryonic stem cells lacking HMGNs show reduced ability to differentiate towards the oligodendrocyte lineage, and mice lacking HMGNs show reduced oligodendrocyte count and decreased spinal cord myelination, and display related neurological phenotypes. Thus, the presence of HMGN proteins is required for proper expression of neural differentiation genes during embryonic stem cell differentiation. Specifically, we demonstrate that the dynamic interplay between HMGNs and H1 in chromatin epigenetically regulates the expression of OLIG1&2, thereby affecting oligodendrocyte development and myelination, and mouse behavior.
An experimental test on time constraint and sexual conflict over parental care

Because parental care is costly, a sexual conflict between parents over parental investment is expected to arise. Parental care behavior is an adaptive decision, involving trade-offs between remating, and consequently desertion of the brood, and continuing parental effort. If the main advantage of desertion is remating, then this will be a time constraint, because the deserting individual will require a certain minimum period of time to breed again in the same breeding season. So, a short breeding season should force certain individuals to desert the first brood to have enough time to successfully complete their second breeding attempt. The rock sparrow, Petronia petronia, is an unusual species in which brood desertion can occur in both sexes and the breeding season is quite short so it is a good species to investigate the role of time constraint on brood desertion. For 3 years, I investigated the brood desertion modality of the rock sparrow. Then, for 2 years, I removed a group of experimental nest boxes during the autumn. Later, I re-installed the experimental nest boxes after the start of the breeding season (2 weeks after the first egg was laid), mimicking a shortening of the breeding season for the (experimental) pairs that used experimental nest boxes. I found that in the experimental pairs, the percentage of deserting individuals was significantly higher than in the control groups, and the deserting individuals were older females. This experiment adds to our knowledge of timing of reproduction effects on individual decisions to desert by showing that a short and delayed breeding season may have different effects on males and females. To my knowledge, this is the first experimental study that demonstrates a direct link between time constraint and brood desertion.
Structural Basis for the Biological Activities of Bovine Seminal Ribonuclease (*)

Bovine seminal ribonuclease (BS-RNase) is a homolog of RNase A with special biological properties that include specific antitumor, aspermatogenic, and immunosuppressive activities. Unlike RNase A, BS-RNase is a dimer cross-linked by disulfide bonds between Cys of one subunit and Cys of the other. At equilibrium, this dimer is a mixture of two distinct quaternary forms, M=M and MM. The conversion of M=M to MM entails the exchange of NH2-terminal α-helices between subunits. Here, the cytotoxic activities of purified MM were shown to be greater than those of purified M=M, despite extensive equilibration of M=M and MM during the time course of the assays. Replacing Cys or Cys with a serine residue did not compromise the enzymatic activity of dimeric BS-RNase, but reduced both the fraction of MM at equilibrium and the cytotoxicity. We conclude that the MM form is responsible for the special biological properties of BS-RNase. Since cytosolic ribonuclease inhibitor binds tightly to monomeric but not dimeric BS-RNase and only the MM form can remain dimeric in the reducing environment of the cytosol, we propose that BS-RNase has evolved its MM form to retain its lethal enzymatic activity in vivo.
Human Disc Phospholipase A2 is Inflammatory

Human discs have been demonstrated to contain high levels of phospholipase A2. As the enzyme responsible for the liberation of arachidonic acid from membranes, this enzyme has a theoretical inflammatory potential. Hernlated lumbar discs have a higher level of phospholipase A2 than do normal discs. The purpose of this study was to evaluate the inflammatory capability of purified human disc phospholipase A2. Phospholipase A2 extracted and purified from human disc was found to be inflammatory. Its inflammatory capability was directly related to its ability to function enzymatically. When the enzyme was treated with parabromophenacyl bromide (p-BPB) to specifically alkylate the active site histidine and block catalytic activity, the ability of the modified protein to produce edema was markedly reduced. Careful regulation of the activity of this enzyme is important in vivo because its inflammatory potential could result in disc degeneration and nerve injury.
Kinematics and line strength indices in the halos of the Coma brightest cluster galaxies NGC 4874 and NGC 4889

Aims. We investigate the stellar kinematics and line strength indices in the outer halos of brightest cluster galaxies (BCGs) in the Coma cluster to obtain the outer halo V rot and σ profiles and to derive constraints on the formation history of these objects. Methods. We analyzed absorption lines in deep, medium-resolution, long-slit spectra in the wavelength range ~4500-5900 A°, out to ~ 50 kpc for NGC 4874 and ~65 kpc for NGC 4889, probing regions with a surface brightness down to μ R ~ 24 mag arcsec -2 . Results. These data provide stellar velocity and velocity dispersion profiles along the major axes of both BCGs, and also along the minor axis of NGC 4889. The kinematic properties of NGC 4874 and NGC 4889 halos extend the previous relations of early-type galaxy halos to bright luminosities and indicate that the stars in the outer regions are still bound to these galaxies. For NGC 4889 we also determine Hβ Mg and Fe line strength indices, finding strong radial gradients for Mg and Fe. The current dataset for NGC 4889 is one of the most extended in radius, including both stellar kinematics and line strength index measurements.
Accumulation of Intrahepatic TNF-α-Producing NKp44+ NK Cells Correlates With Liver Fibrosis and Viral Load in Chronic HCV Infection

AbstractIn the setting of chronic hepatitis C virus (HCV) infection, changes in natural killer (NK) cells have been shown to reflect activation in response to virus stimulation. The contribution of individual natural cytotoxicity receptors to HCV infection remains to be clarified. NKp44 is the sole specific natural cytotoxicity receptor expressed only on activated NK cells.In this study, peripheral blood and liver NK-cell subsets were purified from 31 patients with chronic C hepatitis or nonalcoholic steatohepatitis, and then characterized by flow cytometry. Their polyfunctional activity was determined by expression of the CD107a degranulation marker, together with intracellular cytokine production.Unlike the patients with nonalcoholic steatohepatitis, patients with chronic HCV infection had a higher frequency of NKp44+ NK cells in the liver than in their peripheral blood (P < 0.0001). Intrahepatic NKp44+ NK cells from HCV+ individuals produced higher levels of tumor necrosis factor-&agr; than did NKp44− NK cells (P = 0.0011). Importantly, the frequency of intrahepatic NKp44+ NK cells was correlated with both HCV-RNA levels (P = 0.0234) and stage of fibrosis (P = 0.0003). Our findings suggest that the accumulation of intrahepatic tumor necrosis factor-&agr;-producing NKp44+ resident NK cells play a role in the liver damage associated with chronic HCV infection.
Cross-Protective Potential of a Novel Monoclonal Antibody Directed against Antigenic Site B of the Hemagglutinin of Influenza A Viruses

The hemagglutinin (HA) of influenza A viruses has been classified into sixteen distinct subtypes (H1–H16) to date. The HA subtypes of influenza A viruses are principally defined as serotypes determined by neutralization or hemagglutination inhibition tests using polyclonal antisera to the respective HA subtypes, which have little cross-reactivity to the other HA subtypes. Thus, it is generally believed that the neutralizing antibodies are not broadly cross-reactive among HA subtypes. In this study, we generated a novel monoclonal antibody (MAb) specific to HA, designated MAb S139/1, which showed heterosubtypic cross-reactive neutralization and hemagglutination inhibition of influenza A viruses. This MAb was found to have broad reactivity to many other viruses (H1, H2, H3, H5, H9, and H13 subtypes) in enzyme-linked immunosorbent assays. We further found that MAb S139/1 showed neutralization and hemagglutination-inhibition activities against particular strains of H1, H2, H3, and H13 subtypes of influenza A viruses. Mutant viruses that escaped neutralization by MAb S139/1 were selected from the A/Aichi/2/68 (H3N2), A/Adachi/2/57 (H2N2), and A/WSN/33 (H1N1) strains, and sequence analysis of the HA genes of these escape mutants revealed amino acid substitutions at positions 156, 158, and 193 (H3 numbering). A molecular modeling study showed that these amino acids were located on the globular head of the HA and formed a novel conformational epitope adjacent to the receptor-binding domain of HA. Furthermore, passive immunization of mice with MAb S139/1 provided heterosubtypic protection. These results demonstrate that MAb S139/1 binds to a common antigenic site shared among a variety of HA subtypes and neutralizes viral infectivity in vitro and in vivo by affecting viral attachment to cells. The present study supports the notion that cross-reactive antibodies play some roles in heterosubtypic immunity against influenza A virus infection, and underscores the potential therapeutic utility of cross-reactive antibodies against influenza.
Altered function and expression of the orphan GPR135 at the cardiovascular level in diabetic Wistar rats

Abstract Cardiovascular complications are the main cause of mortality in patients with diabetes, these have been associated with changes in function and expression of receptors coupled to G proteins (GPCR), which include orphan receptors which some of them tend to modify in diabetes, although others are not known, such as GPR135. For this reason, the objective of this work was to study the expression of the orphan receptor GPR135 in brain, heart, kidney, aorta, lung, spleen and liver of diabetic rats, as well as its function by the administration of siRNA (small interfering RNA) and curves to isoproterenol. Our results showed that GPR135 is expressed in all tissues analyzed and its expression is modified due to diabetes, we also observed that the responses to isoproterenol increase in diabetic rats administered with siRNA. Therefore, we conclude that the orphan receptor GPR135 is expressed in different tissues and its expression tends to be modified due to diabetes, besides that it is functional and that it seems to be coupled to Gi/o protein which has negative chronotropic and inotropic effects, therefore, we do not rule out that it participates in the cardiovascular complications associated with diabetes.
Hungarian Medical Students’ Knowledge About and Attitude Toward Homosexual, Bisexual, and Transsexual Individuals

ABSTRACT Discrimination that LGBTQ individuals experience in health care settings might affect their health and intention of using health care services. However, health needs of LGBTQ patients are still inappropriately addressed in the medical curriculum. First-, third-, and fourth-year medical students (N = 569) from the four Hungarian medical universities participated in a study in 2017 to assess knowledge about homosexuality, homonegativity, and their attitude as health care professionals toward sexual minorities. We found that higher levels of knowledge about homosexuality were associated with lower levels of homonegativity, upper-grade level in university, not being religious, and having close LGBTQ acquaintances. Our results suggest that it may be necessary to introduce LGBTQ themes in the medical curricula (not only in Hungary, but also in other countries) in order to improve the knowledge and attitude of medical students and thereby improve the health care of LGBTQ individuals.
A Genetic Screen Using the Drosophila melanogaster TRiP RNAi Collection To Identify Metabolic Enzymes Required for Eye Development

The metabolic enzymes that compose glycolysis, the citric acid cycle, and other pathways within central carbon metabolism have emerged as key regulators of animal development. These enzymes not only generate the energy and biosynthetic precursors required to support cell proliferation and differentiation, but also moonlight as regulators of transcription, translation, and signal transduction. Many of the genes associated with animal metabolism, however, have never been analyzed in a developmental context, thus highlighting how little is known about the intersection of metabolism and development. Here we address this deficiency by using the Drosophila TRiP RNAi collection to disrupt the expression of over 1,100 metabolism-associated genes within cells of the eye imaginal disc. Our screen not only confirmed previous observations that oxidative phosphorylation serves a critical role in the developing eye, but also implicated a host of other metabolic enzymes in the growth and differentiation of this organ. Notably, our analysis revealed a requirement for glutamine and glutamate metabolic processes in eye development, thereby revealing a role of these amino acids in promoting Drosophila tissue growth. Overall, our analysis highlights how the Drosophila eye can serve as a powerful tool for dissecting the relationship between development and metabolism.
Processing and storage effects on blueberry (Vaccinium corymbosum L.) polyphenolics.

Blueberries are commonly consumed in processed forms, but limited information is available on how different processing methods and storage of processed products impact the polyphenolic content of the fruit. In this study, we determined how canning, pureeing and juicing of blueberries, as well as storage of processed products at 25°C, influenced the retention of chlorogenic acid, total flavonols, total anthocyanins, and total procyanidins. The retention of flavonols (5799%) and chlorogenic acid (64-100%) was greater than that of anthocyanins (4272%) and procyanidins (19-78%). The type of processing method impacted polyphenolic retention with canned products showing the greatest retention, followed by pureed products, and juices. Non-clarified juices retained higher levels of chlorogenic acid, total flavonols, and total anthocyanins than clarified juices, but clarified juices contained higher levels of total procyanidins. Significant losses of total anthocyanins and total procyanidins occurred in all processed products stored over six months at 25°C, which most likely was due to polymeric compounds formed as a result of condensation reactions among anthocyanins and procyanidins. In contrast, total flavonols and chlorogenic acid showed much greater retention during storage. Our results indicate that methods are needed to prevent polyphenolic losses during processing, especially in juices, and storage of processed products.
Training Deep Neural Networks via Direct Loss Minimization

Supervised training of deep neural nets typically relies on minimizing cross-entropy. However, in many domains, we are interested in performing well on metrics specific to the application. In this paper we propose a direct loss minimization approach to train deep neural networks, which provably minimizes the application-specific loss function. This is often non-trivial, since these functions are neither smooth nor decomposable and thus are not amenable to optimization with standard gradient-based methods. We demonstrate the effectiveness of our approach in the context of maximizing average precision for ranking problems. Towards this goal, we develop a novel dynamic programming algorithm that can efficiently compute the weight updates. Our approach proves superior to a variety of baselines in the context of action classification and object detection, especially in the presence of label noise.
The Welfare Effects of Transportation Infrastructure Improvements

We develop a general equilibrium geographic framework to characterize the welfare effect of transportation infrastructure investments. We tackle three distinct but conflating challenges: First, we offer an analytical characterization of the routing problem and, in particular, how infrastructure investment between any two connected locations decreases the total trade costs between all pairs of locations. Second, we characterize how this cost reduction affects welfare within a standard general equilibrium geography setup where market inefficiencies arise due to agglomeration and dispersion spillovers. Finally, we show how our framework admits analytical characterizations of traffic congestion, which creates a critical – albeit tractable – feedback loop between trade costs and the general equilibrium economic system. We apply these results to calculate the welfare effects of improving each of the thousands of segments of the U.S. national highway network. We find large but heterogeneous welfare effects, with the largest gains concentrated in metropolitan areas and along important trading corridors.
Volume Weighted Average Price Optimal Execution

We study the problem of optimal execution of a trading order under Volume Weighted Average Price (VWAP) benchmark, from the point of view of a risk-averse broker. The problem consists in minimizing mean-variance of the slippage, with quadratic transaction costs. We devise multiple ways to solve it, in particular we study how to incorporate the information coming from the market during the schedule. Most related works in the literature eschew the issue of imperfect knowledge of the total market volume. We instead incorporate it in our model. We validate our method with extensive simulation of order execution on real NYSE market data. Our proposed solution, using a simple model for market volumes, reduces by 10% the VWAP deviation RMSE of the standard "static" solution (and can simultaneously reduce transaction costs).