Miracle-dz/UniFAR-FTUs huggingface dataset:
Mangiferin Decreases Plasma Free Fatty Acids through Promoting Its Catabolism in Liver by Activation of AMPK

Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism.
Testing the weak‐form efficiency in African stock markets

Purpose – The purpose of this paper is to investigate and compare the weak‐form efficiency of a set of 24 African continent‐wide stock price indices and those of eight individual African national stock price indices.Design/methodology/approach – Variance‐ratio tests based on ranks and signs were used to examine the weak‐form efficiency of the 32 stock price indices investigated.Findings – On average, it was found that irrespective of the test employed, the returns of all the 24 African continent‐wide stock price indices examined in the study are less non‐normally distributed compared to the eight individual national stock price indices examined. The authors also report evidence of the African continent‐wide stock price indices having significantly better weak‐form informational efficiency than their national counterparts.Practical implications – The policy implication of this evidence is that the African equity price discovery process can be significantly improved if African stock markets integrate their .
Phage T4 SegB protein is a homing endonuclease required for the preferred inheritance of T4 tRNA gene region occurring in co-infection with a related phage

Homing endonucleases initiate nonreciprocal transfer of DNA segments containing their own genes and the flanking sequences by cleaving the recipient DNA. Bacteriophage T4 segB gene, which is located in a cluster of tRNA genes, encodes a protein of unknown function, homologous to homing endonucleases of the GIY-YIG family. We demonstrate that SegB protein is a site-specific endonuclease, which produces mostly 3′ 2-nt protruding ends at its DNA cleavage site. Analysis of SegB cleavage sites suggests that SegB recognizes a 27-bp sequence. It contains 11-bp conserved sequence, which corresponds to a conserved motif of tRNA TψC stem-loop, whereas the remainder of the recognition site is rather degenerate. T4-related phages T2L, RB1 and RB3 contain tRNA gene regions that are homologous to that of phage T4 but lack segB gene and several tRNA genes. In co-infections of phages T4 and T2L, segB gene is inherited with nearly 100% of efficiency. The preferred inheritance depends absolutely on the segB gene integrity and is accompanied by the loss of the T2L tRNA gene region markers. We suggest that SegB is a homing endonuclease that functions to ensure spreading of its own gene and the surrounding tRNA genes among T4-related phages.
Activity-Dependent Synaptic Plasticity in Retinal Ganglion Cells

At many excitatory synapses, AMPA-type receptors (AMPARs) are not statically situated in the membrane, but undergo continuous rounds of endocytosis and exocytosis, referred to as rapid cycling. AMPAR cycling is believed to play a role in certain forms of synaptic plasticity, but the link between cycling and synaptic function is not well understood. We have previously demonstrated that AMPARs cycle in neurons of the inner retina, including amacrine and ganglion cells, and that cycling is inhibited by synaptic activity. Recording from cultured neurons and ON ganglion cells in the flat-mount retina, we now show that rapid cycling is primarily, perhaps exclusively, restricted to AMPARs that contain the GluR2 subunit, and that cycle is confined to extrasynaptic receptors. We also demonstrate a form of plasticity at the ON bipolar cell–ON ganglion cell synapse, whereby synaptic quiescence drives a change in the composition of AMPARs from predominantly GluR2-containing to GluR2-lacking. Finally, we provide evidence linking synaptic receptor composition and cycling, showing that disruption of cycling leads increases the number of GluR2-containing receptors in the ON bipolar–ON ganglion cell synapse. We propose that cycling lowers the number of GluR2-containing receptors at the surface and, consequently, within the synapse. After increased levels of synaptic activity, cycling ceases, and all GluR2-containing receptors are free to go to the surface, where they can be delivered to synapses. Our results suggest that by regulating the cycling of AMPARs, ambient light can modulate the composition of synaptic receptors in ON ganglion cells.
Creation of a Genome-Wide Metabolic Pathway Database for Populus trichocarpa Using a New Approach for Reconstruction and Curation of Metabolic Pathways for Plants1[W][OA]

Metabolic networks reconstructed from sequenced genomes or transcriptomes can help visualize and analyze large-scale experimental data, predict metabolic phenotypes, discover enzymes, engineer metabolic pathways, and study metabolic pathway evolution. We developed a general approach for reconstructing metabolic pathway complements of plant genomes. Two new reference databases were created and added to the core of the infrastructure: a comprehensive, all-plant reference pathway database, PlantCyc, and a reference enzyme sequence database, RESD, for annotating metabolic functions of protein sequences. PlantCyc (version 3.0) includes 714 metabolic pathways and 2,619 reactions from over 300 species. RESD (version 1.0) contains 14,187 literature-supported enzyme sequences from across all kingdoms. We used RESD, PlantCyc, and MetaCyc (an all-species reference metabolic pathway database), in conjunction with the pathway prediction software Pathway Tools, to reconstruct a metabolic pathway database, PoplarCyc, from the recently sequenced genome of Populus trichocarpa. PoplarCyc (version 1.0) contains 321 pathways with 1,807 assigned enzymes. Comparing PoplarCyc (version 1.0) with AraCyc (version 6.0, Arabidopsis [Arabidopsis thaliana]) showed comparable numbers of pathways distributed across all domains of metabolism in both databases, except for a higher number of AraCyc pathways in secondary metabolism and a 1.5-fold increase in carbohydrate metabolic enzymes in PoplarCyc. Here, we introduce these new resources and demonstrate the feasibility of using them to identify candidate enzymes for specific pathways and to analyze metabolite profiling data through concrete examples. These resources can be searched by text or BLAST, browsed, and downloaded from our project Web site (http://plantcyc.org).
Efficient Reverse Genetics Generation of Infectious Junin Viruses Differing in Glycoprotein Processing

ABSTRACT The New World arenaviruses, Junin, Machupo, Guanarito, Sabia, and Chapare, are associated with rapidly progressing severe hemorrhagic fever with a high rate of case fatality in various regions of South America. The threat of natural or deliberate outbreaks associated with these viruses makes the development of preventive or therapeutic measures important. Here we describe a Junin virus functional minigenome system and a reverse genetics system for production of infectious Junin virus. This robust, highly efficient system involves transfection of cells with only two plasmids which transcribe the virus S and L antigenomic RNAs. The utility of the system is demonstrated by generating Junin viruses which encode a glycoprotein precursor (GPC) containing the following: (i) the wild-type (SKI-1/S1P peptidase) cleavage site, (ii) no cleavage site, or (iii) a cleavage site where the SKI-1/S1P motif (RSLK) is replaced by a furin cleavage site (RRKR). In contrast to the wild-type virus, Junin virus lacking a GPC cleavage site replicated within successfully transfected cells but failed to yield infectious virus particles. This confirms observations with other arenaviruses suggesting that GPC cleavage is essential for arenavirus infectivity. In contrast, infectious Junin virus which encoded GPC cleaved by furin-like proteases was easily generated. The two-plasmid, high efficiency aspects of this Junin virus reverse genetics system show great promise for addressing important questions regarding arenavirus hemorrhagic fever disease and for development of precisely attenuated live arenavirus vaccines.
SINR Balancing Technique for Downlink Beamforming in Cognitive Radio Networks

We propose a novel signal to interference and noise (SINR) balancing technique for a downlink cognitive radio network (CRN) wherein multiple cognitive users (also referred to as secondary users (SUs)) coexist and share the licensed spectrum with the primary users (PUs) using the underlay approach. The proposed beamforming technique maximizes the worst SU SINR while ensuring that the interference leakage to PUs is below specific thresholds. Due to the additional interference constraints imposed by PUs, the principle of uplink-downlink duality used in the conventional downlink beamformer design cannot be directly applied anymore. To circumvent this problem, using an algebraic manipulation on the interference constraints, we propose a novel SINR balancing technique for CRNs based on uplink-downlink iterative design techniques. Simulation results illustrate the convergence and the optimality of the proposed beamformer design.
Extraintestinal Pathogenic Escherichia coli Strains of Avian and Human Origin: Link between Phylogenetic Relationships and Common Virulence Patterns

ABSTRACT Extraintestinal pathogenic Escherichia coli (ExPEC) strains of human and avian origin show similarities that suggest that the avian strains potentially have zoonotic properties. However, the phylogenetic relationships between avian and human ExPEC strains are poorly documented, so this possibility is difficult to assess. We used PCR-based phylotyping and multilocus sequence typing (MLST) to determine the phylogenetic relationships between 39 avian pathogenic E. coli (APEC) strains of serogroups O1, O2, O18, and O78 and 51 human ExPEC strains. We also compared the virulence genotype and pathogenicity for chickens of APEC strains and human ExPEC strains. Twenty-eight of the 30 APEC strains of serogroups O1, O2, and O18 were classified by MLST into the same subcluster (B2-1) of phylogenetic group B2, whereas the 9 APEC strains of serogroup O78 were in phylogenetic groups D (3 strains) and B1 (6 strains). Human ExPEC strains were closely related to APEC strains in each of these three subclusters. The 28 avian and 25 human strains belonging to phylogenetic subcluster B2-1 all expressed the K1 antigen and presented no significant differences concerning the presence of other virulence factors. Moreover, human strains of this phylogenetic subcluster were highly virulent for chicks, so no host specificity was identified. Thus, APEC strains of serotypes O1:K1, O2:K1, and O18:K1 belong to the same highly pathogenic clonal group as human E. coli strains of the same serotypes isolated from cases of neonatal meningitis, urinary tract infections, and septicemia. These APEC strains constitute a potential zoonotic risk.
Proteome Folding Kinetics Is Limited by Protein Halflife

How heterogeneous are proteome folding timescales and what physical principles, if any, dictate its limits? We answer this by predicting copy number weighted folding speed distribution – using the native topology – for E.coli and Yeast proteome. E.coli and Yeast proteomes yield very similar distributions with average folding times of 100 milliseconds and 170 milliseconds, respectively. The topology-based folding time distribution is well described by a diffusion-drift mutation model on a flat-fitness landscape in free energy barrier between two boundaries: i) the lowest barrier height determined by the upper limit of folding speed and ii) the highest barrier height governed by the lower speed limit of folding. While the fastest time scale of the distribution is near the experimentally measured speed limit of 1 microsecond (typical of barrier-less folders), we find the slowest folding time to be around seconds (8 seconds for Yeast distribution), approximately an order of magnitude less than the fastest halflife (approximately 2 minutes) in the Yeast proteome. This separation of timescale implies even the fastest degrading protein will have moderately high (96%) probability of folding before degradation. The overall agreement with the flat-fitness landscape model further hints that proteome folding times did not undergo additional major selection pressures – to make proteins fold faster – other than the primary requirement to “sufficiently beat the clock” against its lifetime. Direct comparison between the predicted folding time and experimentally measured halflife further shows 99% of the proteome have a folding time less than their corresponding lifetime. These two findings together suggest that proteome folding kinetics may be bounded by protein halflife.
Genetic Analysis of Completely Sequenced Disease-Associated MHC Haplotypes Identifies Shuffling of Segments in Recent Human History

The major histocompatibility complex (MHC) is recognised as one of the most important genetic regions in relation to common human disease. Advancement in identification of MHC genes that confer susceptibility to disease requires greater knowledge of sequence variation across the complex. Highly duplicated and polymorphic regions of the human genome such as the MHC are, however, somewhat refractory to some whole-genome analysis methods. To address this issue, we are employing a bacterial artificial chromosome (BAC) cloning strategy to sequence entire MHC haplotypes from consanguineous cell lines as part of the MHC Haplotype Project. Here we present 4.25 Mb of the human haplotype QBL (HLA-A26-B18-Cw5-DR3-DQ2) and compare it with the MHC reference haplotype and with a second haplotype, COX (HLA-A1-B8-Cw7-DR3-DQ2), that shares the same HLA-DRB1, -DQA1, and -DQB1 alleles. We have defined the complete gene, splice variant, and sequence variation contents of all three haplotypes, comprising over 259 annotated loci and over 20,000 single nucleotide polymorphisms (SNPs). Certain coding sequences vary significantly between different haplotypes, making them candidates for functional and disease-association studies. Analysis of the two DR3 haplotypes allowed delineation of the shared sequence between two HLA class II–related haplotypes differing in disease associations and the identification of at least one of the sites that mediated the original recombination event. The levels of variation across the MHC were similar to those seen for other HLA-disparate haplotypes, except for a 158-kb segment that contained the HLA-DRB1, -DQA1, and -DQB1 genes and showed very limited polymorphism compatible with identity-by-descent and relatively recent common ancestry (<3,400 generations). These results indicate that the differential disease associations of these two DR3 haplotypes are due to sequence variation outside this central 158-kb segment, and that shuffling of ancestral blocks via recombination is a potential mechanism whereby certain DR–DQ allelic combinations, which presumably have favoured immunological functions, can spread across haplotypes and populations.
Peer-to-Peer Similarity Search in Metric Spaces

This paper addresses the efficient processing of similarity queries in metric spaces, where data is horizontally distributed across a P2P network. The proposed approach does not rely on arbitrary data movement, hence each peer joining the network autonomously stores its own data. We present SIMPEER, a novel framework that dynamically clusters peer data, in order to build distributed routing information at super-peer level. SIMPEER allows the evaluation of range and nearest neighbor queries in a distributed manner that reduces communication cost, network latency, bandwidth consumption and computational overhead at each individual peer. SIMPEER utilizes a set of distributed statistics and guarantees that all similar objects to the query are retrieved, without necessarily flooding the network during query processing. The statistics are employed for estimating an adequate query radius for k-nearest neighbor queries, and transform the query to a range query. Our experimental evaluation employs both real-world and synthetic data collections, and our results show that SIMPEER performs efficiently, even in the case of high degree of distribution.
Progression to active tuberculosis, but not transmission, varies by Mycobacterium tuberculosis lineage in The Gambia.

BACKGROUND There is considerable variability in the outcome of Mycobacterium tuberculosis infection. We hypothesized that Mycobacterium africanum was less likely than M. tuberculosis to transmit and progress to tuberculosis disease. METHODS In a cohort study of patients with tuberculosis and their household contacts in The Gambia, we categorized 1808 HIV-negative tuberculosis contacts according to exposure to M. tuberculosis or M. africanum. Positive skin test results indicated transmission, and development of tuberculosis during 2 years of follow-up indicated progression to disease. RESULTS Transmission rates were similar, but rates of progression to disease were significantly lower in contacts exposed to M. africanum than in those exposed to M. tuberculosis (1.0% vs. 2.9%; hazard ratio [HR], 3.1 [95% confidence interval {CI}, 1.1-8.7]). Within M. tuberculosis sensu stricto, contacts exposed to a Beijing family strain were most likely to progress to disease (5.6%; HR relative to M. africanum, 6.7 [95% CI, 2.0-22]). CONCLUSIONS M. africanum and M. tuberculosis transmit equally well to household contacts, but contacts exposed to M. africanum are less likely to progress to tuberculosis disease than those exposed to M. tuberculosis. The variable rate of progression by lineage suggests that tuberculosis variability matters in clinical settings and should be accounted for in studies evaluating tuberculosis vaccines and treatment regimens for latent tuberculosis infection.
RAB-5 Controls the Cortical Organization and Dynamics of PAR Proteins to Maintain C. elegans Early Embryonic Polarity

In all organisms, cell polarity is fundamental for most aspects of cell physiology. In many species and cell types, it is controlled by the evolutionarily conserved PAR-3, PAR-6 and aPKC proteins, which are asymmetrically localized at the cell cortex where they define specific domains. While PAR proteins define the antero-posterior axis of the early C. elegans embryo, the mechanism controlling their asymmetric localization is not fully understood. Here we studied the role of endocytic regulators in embryonic polarization and asymmetric division. We found that depleting the early endosome regulator RAB-5 results in polarity-related phenotypes in the early embryo. Using Total Internal Reflection Fluorescence (TIRF) microscopy, we observed that PAR-6 is localized at the cell cortex in highly dynamic puncta and depleting RAB-5 decreased PAR-6 cortical dynamics during the polarity maintenance phase. Depletion of RAB-5 also increased PAR-6 association with clathrin heavy chain (CHC-1) and this increase depended on the presence of the GTPase dynamin, an upstream regulator of endocytosis. Interestingly, further analysis indicated that loss of RAB-5 leads to a disorganization of the actin cytoskeleton and that this occurs independently of dynamin activity. Our results indicate that RAB-5 promotes C. elegans embryonic polarity in both dynamin-dependent and -independent manners, by controlling PAR-6 localization and cortical dynamics through the regulation of its association with the cell cortex and the organization of the actin cytoskeleton.
GPR55-dependent and -independent ion signalling in response to lysophosphatidylinositol in endothelial cells

Background and purpose: The glycerol‐based lysophospholipid lysophosphatidylinositol (LPI) is an endogenous agonist of the G‐protein‐coupled receptor 55 (GPR55) exhibiting cannabinoid receptor‐like properties in endothelial cells. To estimate the contribution of GPR55 to the physiological effects of LPI, the GPR55‐dependent and ‐independent electrical responses in this cell type were investigated.
The Revelation Principle for Mechanism Design with Reporting Costs

The revelation principle is a key tool in mechanism design. It allows the designer to restrict attention to the class of truthful mechanisms, greatly facilitating analysis. This is also borne out in an algorithmic sense, allowing certain computational problems in mechanism design to be solved in polynomial time. Unfortunately, when not every type can misreport every other type (the partial verification model), or, more generally, misreporting can be costly, the revelation principle can fail to hold. This also leads to NP-hardness results. The primary contribution of this paper consists of characterizations of conditions under which the revelation principle still holds when misreporting can be costly. (These are generalizations of conditions given earlier for the partial verification case [Green and Laffont 1986; Yu 2011].) We also study associated computational problems.
X-Ray Observations of the Coma Cluster in a Broad Energy Band with the INTEGRAL, RXTE, and ROSAT Observatories

We present results of X-ray observations of the Coma Cluster with multiple instruments over a broad energy band. Using the data from the INTEGRAL, RXTE, and ROSAT observatories, we find that the Coma spectrum in the 0.5–107 keV energy band can be well approximated by a thermal plasma emission model with a temperature of T = 8.2 keV. INTEGRAL was used to image the cluster emission in the hard energy band. The cluster is only marginally detectable (~1.6 σ) in the 44–107 keV energy band; however, the raw flux in this band is consistent with the previous results from the BeppoSAX and RXTE observatories. We can exclude with high significance that the hard-band flux reported by BeppoSAX and RXTE could be produced by a single point source. The 20–80 keV flux of a possible nonthermal component in the cluster spectrum is (6.0 ± 8.8) × 10−12 ergs cm−2 s−1. Using the upper limits on nonthermal flux, we obtain a lower limit on magnetic field of 0.1-0.2 μG (depending on the spatial model for a smoothly varying field). We also present a temperature map of the central part of the cluster, which shows significant variations and, in particular, a hot ~11.5 keV region in the extension toward the subcluster infalling from the southwest.