Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in global brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

Lysergic acid diethylamide (LSD) is a psychedelic drug with predominantly agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, the specific receptor contributions to its neurobiological effects remain largely unknown. To address this knowledge gap, we conducted a double-blind, randomized, counterbalanced, cross-over study during which 24 healthy participants received either i) placebo+placebo, ii) placebo+LSD (100 μg po), or iii) ketanserin – a selective 5-HT2A receptor antagonist. Here we focus on resting-state fMRI, a measure of spontaneous neural fluctuations that can map functional brain connectivity. We collected resting-state data 75 and 300 minutes after LSD/placebo administration. We quantified resting-state functional connectivity via a fully data-driven global brain connectivity (GBC) method to comprehensively map LSD neuropharmacological effects. LSD administration caused widespread GBC alterations that followed a specific topography: LSD reduced connectivity in associative areas, but concurrently increased connectivity across sensory and somatomotor areas. The 5-HT2A receptor antagonist, ketanserin, fully blocked the subjective and neural LSD effects. We show that whole-brain data-driven spatial patterns of LSD effects matched 5-HT2A receptor cortical gene expression in humans, which along with ketanserin effects, strongly implicates the 5-HT2A receptor in LSD’s neuropharmacology. Critically, the LSD-induced subjective effects were associated with somatomotor networks GBC changes. These data-driven neuropharmacological results pinpoint the critical role of 5-HT2A in LSD’s mechanism, which informs its neurobiology and guides rational development of psychedelic-based therapeutics
Haplotype Analysis of TNFA Gene in Peptic Ulcer Patients

Abstract The TNFA gene product TNF-? is a cytokine promoting an immune response after bacterial infections. An excessive production of the cytokine is thought to be connected with Helicobacter pylori-induced disorders like gastritis, peptic ulcer disease (PUD), intestinal metaplasia, or even gastric cancer. The synthesis of TNF-á is controlled at transcriptional level and dependent on single nucleotide polymorphisms (SNPs) of TNFA promoter region. SNPs assembled in haplotype have been implicated as potential risk factors for various autoimmune and infectious diseases. The aim of this study was to determine the frequencies of TNFA haplotypes composed of the four common single-nucleotide polymorphisms of the gene (-1031C>T: rs1799964, -863C>A: rs1800630, - 857C>T: rs1799724, -308G>A: rs1800629) in peptic ulcer patients and to assess the significance of the haplotypes as the risk factors of H. pylori infection development. 203 peptic ulcer patients were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Haplotypes and degree of linkage disequilibrium (LD) were inferred with PHASE 2.1 and EMLD software. There was no statistically significant difference in haplotype frequencies between the H. pylori-infected and-uninfected peptic ulcer cases (p=0.62). Analogous association was also absent in the subgroups: peptic ulcer woman (p=0.69), peptic ulcer men (p=0.17). The locus pairs -308_-857, -863_-1031, and -857_-1031 was found to be in very strong L¯D , -308_-1031 and -857 and -863 in strong LD, and -308_-863 - in modest LD. TNFA haplotype structure is not connected with individual differences in susceptibility to development of H. pylori infection in peptic ulcer patients.
Competition in store complexity takes us halfway between Diamond and Bertrand

We consider a new, dynamic price search model with fixed or random deadlines to study in detail how consumers search within and across stores during a single search spell. To endogenize the intensity of competition, we allow firms to adjust freely the level of frictions in their online stores. Interestingly, this pins down uniquely the numbers of informed and uninformed consumers. We show that there exist two similar inefficient equilibria, both with a prominent firm and a non-prominent firm, where these numbers are exactly the same. The outcome is thereby precisely halfway between Diamond equilibrium and Bertrand equilibrium. JEL Classification: D43, D83
Using Genetic and Phenotypic Comparisons to Evaluate Apparent Segregation among Kokanee Spawning Groups

AbstractGenetic and phenotypic traits of spatially and temporally segregated kokanee Oncorhynchus nerka spawning groups in Lake Pend Oreille, Idaho, were compared to test for evidence of divergence on the basis of ecotype (stream- versus shore-spawning) and spawn timing, and to describe morphological, life history, and reproductive variation within and among groups. Early and late spawning runs were found to be reproductively isolated; however, there was no clear evidence of genetic differentiation between ecotypes. Spawning groups within the same ecotype differed in length, age distribution, mean-length-at-age, fecundity, and egg size. Variation in reproductive attributes was due primarily to differences in length distributions. Larger-bodied shore-spawning kokanee were located in areas where egg survival is known to be enhanced by downwelling, suggesting that the distribution of shore-spawning kokanee may be partly structured by competition for spawning habitats with groundwater influence. This study co.
Distinctive cerebral neuropathology in an adult case of SANDO syndrome

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/nan.12429 This article is protected by copyright. All rights reserved. PROFESSOR HERBERT BUDKA (Orcid ID : 0000-0002-1933-1577)
Flux balance analysis in the era of

Flux balance analysis (FBA) has emerged as an effective means to analyse biological networks in a quantitative manner. Much progress has been made on the extension of FBA to incorporate a priori biological knowledge, provide more practical descriptions of observed cell behaviours, and predict the outcome of network perturbations. Metabolomics is independently advancing as a set of high-throughput data acquisition tools providing dynamic profiles of metabolites in an unbiased manner. These data sets are neither yet sufficiently comprehensive nor accurate enough for generating large-scale kinetic models. Thus, there is a pressing need to develop quantitative techniques that can make use of the emerging data and embrace the associated uncertainties. This article reviews recent advances in FBA to meet this need and discusses the utility of FBA as a complement to metabolomics and the expected synergy as a result of combining these two techniques.
Ajuste de modelos de crescimento em frangos de corte

The objective of this work was to investigate adjustments of the Gompertz, Logistic, von Bertalanffy, and Richards growth models, in male and female chickens of the Cobb 500, Ross 308, and Hubbard Flex lines. Initially, 1,800 chickens were randomly housed in 36 pens, with six replicates per lineage and sex, fed ad libitum with feed according to gender, and bred until 56 days of age. Average weekly body weight for each line and sex was used to estimate model parameters using the ordinary least squares, weighted by the inverse variance of the body weight and weighted with a first-order autocorrelated error structure. Weighted models and weighted autocorrelated error models showed different parameter values when compared with the unweighted models, modifying the inflection point of the curve and according to the adjusted coefficient of determination, and the standard deviation of the residue and Akaike information criteria exhibited optimal adjustments. Among the models studied, the Richards and the Gompertz models had the best adjustments in all situations, with more realistic parameter estimates. However, the weighted Richards model, with or without ponderation with the autoregressive first order model AR (1), exhibited the best adjustments in females and males, respectively.
Archaeogenetics of Late Iron Age Çemialo Sırtı, Batman: Investigating maternal genetic continuity in North Mesopotamia since the Neolithic

North Mesopotamia has witnessed dramatic political and social change since the Bronze Age, but the impact of these events on its demographic history is little understood. Here we study this question by analysing the recently excavated Late Iron Age settlement of Çemialo Sırtı in Batman, southeast Turkey. Archaeological and/or radiocarbon evidence indicate that the site was inhabited during two main periods: the first half of the 2nd millennium BCE and the first millennium BCE. Çemialo Sırtı reveals nomadic items of the Early Iron Age, as well as items associated with the Late Achaemenid and subsequent Hellenistic Periods. Mitochondrial DNA (mtDNA) haplotypes from 12 Çemialo Sırtı individuals reveal high genetic diversity in this population, conspicuously higher than early Holocene west Eurasian populations, which supports the notion of increasing population admixture in west Eurasia through the Holocene. Still, in its mtDNA composition, Çemialo Sırtı shows highest affinity to Neolithic north Syria and Neolithic Anatolia among ancient populations studied, and to modern-day southwest Asian populations. Population genetic simulations do not reject continuity between Neolithic and Iron Age, nor between Iron Age and present-day populations of the region. Despite the region’s complex political history and indication for increased genetic diversity over time, we find no evidence for sharp shifts in north Mesopotamian maternal genetic composition within the last 10,000 years.
An integrated multimedia communication system for enterprise networks

Recent advances in high performance computers and high speed broadband networks have opened the realms of exciting new enterprise wide multimedia applications. Broadband multimedia applications over enterprise networks requires appropriate communication protocols and enhanced networking infrastructure to provide sufficient quality of service. Our paper presents an architecture of a communication system for manufacturing multimedia applications. The architecture guarantees better quality of service for real-time multimedia applications. It is based on an ATM intelligent network interface board based on a processor and a field programmable gate array components. The board implements flexible high-level real-time data services and relieves the host from networking load. The board implements a manufacturing message specification (MMS) multimedia application service element.
Epigenetic activation of meiotic recombination in Arabidopsis centromeres via loss of H3K9me2 and non-CG DNA methylation

Eukaryotic centromeres contain the kinetochore, which connects chromosomes to the spindle allowing segregation. During meiosis centromeres are suppressed for crossovers, as recombination in these regions can cause chromosome mis-segregation. Plant centromeres are surrounded by repetitive, transposon-dense heterochromatin that is epigenetically silenced by histone 3 lysine 9 dimethylation (H3K9me2), and DNA methylation in CG and non-CG sequence contexts. Here we show that disruption of Arabidopsis H3K9me2 and non-CG DNA methylation pathways increases meiotic DNA double strand breaks (DSBs) within centromeres, whereas crossovers increase within pericentromeric heterochromatin. Increased pericentromeric crossovers in H3K9me2/non-CG mutants occurs in both inbred and hybrid backgrounds, and involves the interfering crossover repair pathway. Epigenetic activation of recombination may also account for the curious tendency of maize transposon Ds to disrupt CHROMOMETHYLASE3 when launched from proximal loci. Thus H3K9me2 and non-CG DNA methylation exert differential control of meiotic DSB and crossover formation in centromeric and pericentromeric heterochromatin.
Effects of Bisphenol A on Incidence and Severity of Cardiac Lesions in the NCTR-Sprague-Dawley Rat: A CLARITY-BPA Study

The goal of this study was to determine whether bisphenol A (BPA) had adverse effects indicative of cardiac toxicity. As part of the “Consortium Linking Academic and Regulatory Insights on BPA Toxicity” (CLARITY-BPA), study dams and offspring were exposed by daily gavage to five doses of BPA ranging from 2.5 to 25000 μg/kg/day, 0.05 or 0.5 μg/kg/day 17α-ethinyl-estradiol (EE) or 0.3% carboxymethylcellulose vehicle. Exposure-related effects were analyzed in isolated hearts by quantitative morphometry and histopathology. No dose-related changes in body weight were detected. Across all exposure groups including vehicle controls, body weight of continuously dosed males was reduced compared to males dosed only until PND21. Heart weight was increased only in females exposed to EE, and consistent alterations in LV wall thickness were not observed. Exposure-related changes in collagen accumulation were minor and limited to highest EE exposure groups with increased collagen accumulation in PND21 males. Decreased collagen was observed in hearts of BPA or EE exposed females at PND90 and PND180. In BPA or EE treated females cardiomyopathy incidence and severity was significantly increased compared to control females at PND21 with myocardial degeneration observed in both males and females at PND21 and PND90.
Changing geographic patterns and risk factors for avian influenza A(H7N9) infection in China

The 5th epidemic wave in 2016-2017 of avian influenza A(H7N9) virus in China caused more human cases than any previous waves but the factors that may explain the recent range expansion and surge in incidence remain unknown. We investigated the effect of anthropogenic, poultry and wetland information and of market closures on all epidemic waves (1-5). Poultry predictor variables recently became much more important than before, supporting the assumption of much wider H7N9 transmission in the chicken reservoir, that could be linked to increases in pathogenicity. We show that the future range expansion of H7N9 to northern China may translate into a higher risk of coinciding peaks with those of seasonal influenza, leading to a higher risk of reassortments. Live-poultry market closures are showed to be effective in reducing the local incidence rates of H7N9 human cases, but should be paired with other prevention and control measures to prevent transmission.
Elucidating relations between fMRI, ECoG and EEG through a common natural stimulus

Human brain activity can be studied at different spatial and temporal scales using fMRI, ECoG and EEG. To assess how reliably these imaging methods reflect brain responses related to a complex audio-visual stimulus and how similar stimulus-related responses are across methods, we presented a movie clip twice to three different cohorts of subjects (NEEG = 45, NfMRI = 11, NECoOG = 5) and assessed correlations across viewings and imaging methods within a standardized brain space. Grand-average broad-band EEG and low-frequency (4–28 Hz) EEG power reached similar levels of inter-subject reliability as grand-average fMRI and single-subject high-frequency (28116 Hz) ECoG power. ECoG power was negatively correlated with fMRI in low frequencies and positively correlated in high frequencies in temporal and occipital brain areas. Low-frequency EEG power was negatively correlated with fMRI in occipital and parietal, but positively correlated in temporal areas. We also observed strong correlations between fMRI and infra-slow EEG voltage fluctuations.
Intercellular Communication via the comX-Inducing Peptide (XIP) of Streptococcus mutans

ABSTRACT Gram-positive bacteria utilize exported peptides to coordinate genetic and physiological processes required for biofilm formation, stress responses, and ecological competitiveness. One example is activation of natural genetic competence by ComR and the comX-inducing peptide (XIP) in Streptococcus mutans. Although the competence pathway can be activated by the addition of synthetic XIP in defined medium, the hypothesis that XIP is able to function as an intercellular signaling molecule has not been rigorously tested. Coculture model systems were developed that included a “sender” strain that overexpressed the XIP precursor (ComS) and a “responder” strain harboring a green fluorescent protein (GFP) reporter fused to a ComR-activated gene (comX) promoter. The ability of the sender strain to provide a signal to activate GFP expression was monitored at the individual cell and population levels using (i) planktonic culture systems, (ii) cells suspended in an agarose matrix, or (iii) cells growing in biofilms. XIP was shown to be freely diffusible, and XIP signaling between the S. mutans sender and responder strains did not require cell-to-cell contact. The presence of a sucrose-derived exopolysaccharide matrix diminished the efficiency of XIP signaling in biofilms, possibly by affecting the spatial distribution of XIP senders and potential responders. Intercellular signaling was greatly impaired in a strain lacking the primary autolysin, AtlA, and was substantially greater when the sender strain underwent lysis. Collectively, these data provide evidence that S. mutans XIP can indeed function as a peptide signal between cells and highlight the importance of studying signaling with an endogenously produced peptide(s) in populations in various environments and physiologic states. IMPORTANCE The comX-inducing peptide (XIP) of Streptococcus mutans is a key regulatory element in the activation of genetic competence, which allows cells to take up extracellular DNA. XIP has been found in cell culture fluids, and the addition of synthetic XIP to physiologically receptive cells can robustly induce competence gene expression. However, there is a lack of consensus as to whether XIP can function as an intercellular communication signal. Here, we show that XIP indeed signals between cells in S. mutans, but that cell lysis may be a critical factor, as opposed to a dedicated secretion/processing system, in allowing for release of XIP into the environment. The results have important implications in the context of the ecology, virulence, and evolution of a ubiquitous human pathogen and related organisms.
Estimation of Lactate Dehydrogenase Activity in cerebrospinal fluid in different types of meningitis

Objective: Meningitis is life-threatening condition and examination of the Cerebrospinal fluid (CSF) may not give a precise diagnosis and prognosis of different types of meningitis. Bacterial meningitis is still a very common problem especially in many developing countries. The aims of study are to estimate the importance and significance of Lactate Dehydrogenase (LDH), protein and sugar in CSF of different types of meningitis. Methods: A total of 160 cases, aged between 1 month and 60 years, including patients with bacterial meningitis (n=50), pyogenic meningitis (n=46), viral meningitis (n=24) and a control group (n=40), were analyzed on the basis of data from the initial clinical examinations. Results: Significant increase in LDH level (P<0.001) were observed in the test group when compared to the control group. The LDH activity was significantly elevated in the CSF and serum (p < 0.001) in cases of pyogenic (PM) as well as tuberculous meningitis (TBM). Bacterial meningitis is more common than non bacterial meningitis. The enzymatic activity of LDH although significantly raised in PM compared to TBM but there was no cutoff level to differentiate them. The LDH level did rise quite significantly in pyogenic meningitis.
Cytogenetic Studies on Railway Engine Drivers Exposed to Extremely Low Frequency Electromagnetic Fields (ELF-EMF)

Abstract Electric train engine drivers are occupationally exposed to relatively high magnetic field flux densities, while exposure to the other genotoxic agents is considered to be low or non-existent. The present study aimed to analyze the Chromosomal Aberrations (CAs) and Sister Chromatid Exchange (SCE) frequencies among the railway engine drivers occupationally exposed to ELF–EMF. Additionally, to know the synergestic/co–mutagenic effects, the blood samples of these individuals were exposed in vitroto 6ng/ml Mitomycin–C (MMC) and Chromosomal Aberrations (CAs) were studied. The results of the present study do not give any support to the hypothesis that occupational exposure to ELF–EMF can exert a genotoxic effect in these exposed individuals. In addition, it seems that ELF–EMF exposure along with Mitomycin–C (MMC) treatments does not influence the levels of Chromosomal Aberrations (CAs), indicating no possibility of synergestic/co–mutagenic effects.
An atlas of genetic variation for linking pathogen-induced cellular traits to human disease

Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with disease. To facilitate moving from associations to disease mechanisms, we leveraged the role of pathogens in shaping human evolution with the Hi-HOST Phenome Project (H2P2): a catalog of cellular GWAS comprised of 79 phenotypes in response to 8 pathogens in 528 lymphoblastoid cell lines. Seventeen loci surpass genome-wide significance (p<5×10−8) for phenotypes ranging from pathogen replication to cytokine production. Combining H2P2 with clinical association data from the eMERGE Network and experimental validation revealed evidence for mechanisms of action and connections with diseases. We identified a SNP near CXCL10 as a cis-cytokine-QTL and a new risk factor for inflammatory bowel disease. A SNP in ZBTB20 demonstrated pleiotropy, partially mediated through NFκB signaling, and was associated with viral hepatitis. Data are available in an H2P2 web portal to facilitate further interpreting human genome variation through the lens of cell biology.
Modeling--A Tool for Experimentalists

Molecular modeling comprises a broad range of computer methods that allow chemists to display molecules, to predict their structures, to make short movies of molecular motions, to predict how molecules bind to each other, and even to predict how molecules will react. As molecule modeling becomes more routine and more reliable, experimentalists are increasingly using modeling to guide and improve experiments and to answer questions impossible to examine experimentally. This article discusses numerous approaches to and applications of molecular modeling.