Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic structure in village dogs reveals a Central Asian domestication origin

Significance Dogs were the first domesticated species, but the precise timing and location of domestication are hotly debated. Using genomic data from 5,392 dogs, including a global set of 549 village dogs, we find strong evidence that dogs were domesticated in Central Asia, perhaps near present-day Nepal and Mongolia. Dogs in nearby regions (e.g., East Asia, India, and Southwest Asia) contain high levels of genetic diversity due to their proximity to Central Asia and large population sizes. Indigenous dog populations in the Neotropics and South Pacific have been largely replaced by European dogs, whereas those in Africa show varying degrees of European vs. indigenous African ancestry. Dogs were the first domesticated species, originating at least 15,000 y ago from Eurasian gray wolves. Dogs today consist primarily of two specialized groups—a diverse set of nearly 400 pure breeds and a far more populous group of free-ranging animals adapted to a human commensal lifestyle (village dogs). Village dogs are more genetically diverse and geographically widespread than purebred dogs making them vital for unraveling dog population history. Using a semicustom 185,805-marker genotyping array, we conducted a large-scale survey of autosomal, mitochondrial, and Y chromosome diversity in 4,676 purebred dogs from 161 breeds and 549 village dogs from 38 countries. Geographic structure shows both isolation and gene flow have shaped genetic diversity in village dog populations. Some populations (notably those in the Neotropics and the South Pacific) are almost completely derived from European stock, whereas others are clearly admixed between indigenous and European dogs. Importantly, many populations—including those of Vietnam, India, and Egypt—show minimal evidence of European admixture. These populations exhibit a clear gradient of short-range linkage disequilibrium consistent with a Central Asian domestication origin.
The Age of the Paleoindian Assemblage at Sheriden Cave, Ohio

Direct dating of a Paleoindian bone point from Sheriden Cave, Ohio, yielded a radiocarbon age of 10,915 ± 30 ¹⁴C yr B.P. (UCIAMS-38249). This date was derived on highly purified bone collagen. This bone point was found in association with another bone projectile point and a reworked, fluted Clovis projectile point. The artifacts from Sheriden Cave fall within the age range of other Clovis sites in North America, dating to the late Allerød, before the start of the Younger Dryas.
Dalcetrapib, a cholesteryl ester transfer protein modulator

Introduction: Cholesteryl ester transfer protein (CETP) plays an important role in reverse cholesterol transport by transferring cholesteryl esters from high-density lipoprotein (HDL) to the apolipoprotein B-containing lipoproteins. Inhibition of CETP is a target to increase HDL-cholesterol and potentially reduce atherosclerosis. Dalcetrapib is an orally administered CETP inhibitor developed for the treatment of primary hypercholesterolaemia and mixed hyperlipidaemia. Areas covered: Areas covered are: mode of action, preclinical development and clinical trials of dalcetrapib, a CETP modulator. The article provides an understanding of the pharmacokinetic and pharmacodynamic characteristics of dalcetrapib and insight into its clinical efficacy and safety. In clinical trials, dalcetrapib produced significant elevations in HDL-cholesterol when taken alone or in combination with statin with no effect on blood pressure or expression of genes involved in the renin–angiotensin–aldosterone system. Expert opinion: Although dalcetrapib is the least potent CETP inhibitor, it does not impair the formation of CETP-induced pre-β HDL, which might be needed to increase reverse cholesterol transport. While dalcetrapib is well-tolerated and does not show major side effects, the recent interim results of the Phase III dal-OUTCOMES trial have shown the lack of a clinically meaningful benefit, and further testing of the drug has been halted.
A20 Is a Negative Regulator of IFN Regulatory Factor 3 Signaling1

IFN regulatory factor 3 (IRF-3) is a critical transcription factor that regulates an establishment of innate immune status following detection of viral pathogens. Recent studies have revealed that two IκB kinase (IKK)-like kinases, NF-κB-activating kinase/Traf family member-associated NF-κB activator-binding kinase 1 and IKK-i/IKKε, are responsible for activation of IRF-3, but the regulatory mechanism of the IRF-3 signaling pathway has not been fully understood. In this study, we report that IRF-3 activation is suppressed by A20, which was initially identified as an inhibitor of apoptosis and inducibly expressed by dsRNA. A20 physically interacts with NF-κB-activating kinase/Traf family member-associated NF-κB activator-binding kinase 1 and IKK-i/IKKε, and inhibits dimerization of IRF-3 following engagement of TLR3 by dsRNA or Newcastle disease virus infection, leading to suppression of the IFN stimulation response element- and IFN-β promoter-dependent transcription. Importantly, knocking down of A20 expression by RNA interference results in enhanced IRF-3-dependent transcription triggered by the stimulation of TLR3 or virus infection. Our study thus demonstrates that A20 is a candidate negative regulator of the signaling cascade to IRF-3 activation in the innate antiviral response.
Activation of an SP Binding Site Is Crucial for the Expression of Claudin 1 in Rat Epididymal Principal Cells1

Abstract Claudin 1 (CLDN1) is a tight junctional protein present in the epididymis. Limited information exists regarding the regulation of Cldn1 transcription. In the epididymis, the regulation of the 5′ flanking region of genes coding for tight junctional proteins is unknown. The present objectives were to investigate the transcriptional regulation of the Cldn1 gene in the rat epididymis. A 1.8-kb sequence of the 5′ flanking region of the rat Cldn1 gene was cloned. The transcriptional start site is an adenine located at the −198 position relative to the first codon, and 26 bp downstream of the putative TATA box. It is the only start site for the Cldn1 gene transcription in the rat epididymis. The Cldn1 promoter was inserted into a luciferase gene expression vector and transfected into a rat caput epididymal cell line (RCE-1). Sequential deletion analysis revealed that minimal promoter activity was achieved with the construct containing −61 to +164 bp of the promoter. This sequence contained a TATA box and two consensus SP1 binding sites. Electrophoretic mobility shift and supershift assays confirmed that SP1 and SP3 were present in RCE-1 cells and epididymal nuclear extracts, and that they bind to the 5′ SP1 binding motif of the promoter. Site-directed mutagenesis of the 5′ SP1 binding site resulted in a 4-fold decrease in transactivation of the minimal promoter sequence. These findings indicate that SP1 and SP3 bind to the Cldn1 promoter region, and that this interaction influences the expression of Cldn1 in the rat epididymis.
Social Stress Induces Glucocorticoid Resistance in Subordinate Animals

Introducing an aggressive intruder into a cage of mice (social disruption, SDR) resulted in intense fighting and defeat of the cage residents. Defeat was accompanied by elevated levels of serum corticosterone and nerve growth factor (NGF). Repeated exposure to an intruder induced a state of glucocorticoid resistance in peripheral immune cells. The present study sought to examine the behavioral factors that mediated the development of glucocorticoid resistance following SDR. Glucocorticoid resistance developed in animals that exhibited a subordinate behavioral profile, which consisted of a low tendency for social investigation and a high level of submissive behavior in response to the intruder's attacks. Glucocorticoid resistance was also linked to the presence of injuries due to fighting, but not to changes in systemic levels of either corticosterone or NGF. Since a submissive behavioral profile is associated with increased risk for injuries due to fighting, it may be that the development of glucocorticoid resistance is an adaptive mechanism that allows the inflammatory component of wound healing to occur in the presence of high levels of corticosterone. Together, these findings demonstrate that the outcomes of social stress may be modified by physiological changes associated with wounding, as well as by behavioral variables such as social status.
Receptor mimicry as novel therapeutic treatment for biothreat agents

The spectre of intentional release of pathogenic microbes and their toxins is a real threat. This article reviews the literature on adhesins of biothreat agents, their interactions with oligosaccharides and the potential for anti-adhesion compounds as an alternative to conventional therapeutics. The minimal binding structure of ricin has been well characterised and offers the best candidate for successful anti- adhesion therapy based on the Galβ1-4GlcNAc structure. The botulinum toxin serotypes A-F bind to a low number of gangliosides (GT1b, GQ1b, GD1a and GD1b) hence it should be possible to determine the minimal structure for binding. The minimal disaccharide sequence of GalNAcβ1-4Gal found in the gangliosides asialo-GM1 and asialo-GM2 is required for adhesion for many respiratory pathogens. Although a number of adhesins have been identified in bacterial biothreat agents such as Yersinia pestis, Bacillus anthracis, Francisella tularensis, Brucella species and Burkholderia pseudomallei, specific information regarding their in vivo expression during pneumonic infection is lacking. Limited oligosaccharide inhibition studies indicate the potential of GalNAcβ1-4Gal, GalNAcβ-3Gal and the hydrophobic compound, para-nitrophenol as starting points for the rational design of generic anti- adhesion compounds. A cocktail of multivalent oligosaccharides based on the minimal binding structures of identified adhesins would offer the best candidates for anti-adhesion therapy.
Morphological changes in the position of the mandibular foramen in dentate and edentate Brazilian subjects

This study assessed the mandibular foramen (MF) position variability in dentate and edentate Brazilian mandibles. Eighty dentate and 79 edentate mandibles of unknown sex were measured bilaterally using a digital caliper (0.1‐mm precision). Horizontal linear measurements (HM) were done from the MF to the anterior border of the mandibular ramus (MF‐A) and from the MF to the posterior border of the mandibular ramus (MF‐B). Vertical linear measurements (VM) were done from the MF to the most inferior point of the mandibular notch (MF‐C) and from the MF to the inferior border of the mandibular ramus (MF‐D). Data were analyzed by two‐way ANOVA (alpha = 5%). The HM means and standard deviations (±SD) for MF‐A were, edentate right (ER): 17.5 (±3.2) mm, edentate left (EL): 17.4 (±3.4) mm, dentate right (DR): 19.2 (±3.6) mm, and dentate left (DL): 18.8 (±3.8) mm. The means (±SD) for the MF‐B measurements were, respectively, ER: 12.8 (±2.4) mm, EL: 12.9 (±2.3) mm, DR: 14.2 (±2.4) mm, and DL: 13.9 (±2.6) mm. The VM values for the MF‐C measurements were, ER: 23.4 (±3.8) mm, EL: 22.9 (±3.7) mm, DR: 23.6 (±3.1) mm, and DL: 23.1 (±3) mm, and for the MF‐D measurements, ER: 26.4 (±4.2) mm, EL: 26.4 (±4) mm, DR 28.3 (±3.9) mm, and DL 28 (±3.8) mm. Side had no influence (p>0.05) on any edentate or dentate mandible measurement. Dentate mandible measurements showed statistically significant differences compared to the edentate mandibles, except for MF‐C. The mandibular foramen position changes with loss of teeth and this variability may be responsible for occasional failure of inferior alveolar nerve block. Clin. Anat. 23:394–398, 2010. © 2010 Wiley‐Liss, Inc.
Helical and electron beam CT scanning in the evaluation of renal vein involvement in patients with renal cell carcinoma.

PURPOSE The purpose of this study was to assess helical and electron beam CT scanning in the evaluation of renal vein involvement in patients with renal cell carcinoma (RCC). METHOD Seventy-three patients with 76 pathologically proven RCC who underwent surgical resection or autopsy were evaluated for the accuracy of helical and electron beam CT scanning in the detection of renal vein tumor thrombus in patients with RCC. Patients were entered into the study only if they were scanned on either electron beam or helical CT scanners with intravenous contrast medium enhancement. The tumors involved the right kidney in 38 cases and the left kidney in 38 cases, with tumor size ranging from 1.5 to 19 cm (mean 7 cm). The pathologic grade of the tumor was Grade I in 21, Grade II in 37, Grade III in 15, and Grade IV, in 3 patients. RESULTS The accuracy of preoperative CT evaluation of the renal vein for presence or absence of tumor thrombus was 96%. The negative predictive value was 97% and the positive predictive value was 92%. Sensitivity was 85% with a specificity of 98%. In two cases we were unable to detect small intrarenal venous thrombus, although this was present on a microscopic level and did not affect surgical resection. A single false-positive CT result occurred secondary to unopacified blood flow from a capsular vein into the affected renal vein, resulting in a small flow void on CT. CONCLUSION The data show that preoperative staging of the renal vein in the patients with RCC is effectively provided with helical and electron beam CT scanning.
Polyphenol-Rich Dry Common Beans (Phaseolus vulgaris L.) and Their Health Benefits

Polyphenols are plant metabolites with potent anti-oxidant properties, which help to reduce the effects of oxidative stress-induced dreaded diseases. The evidence demonstrated that dietary polyphenols are of emerging increasing scientific interest due to their role in the prevention of degenerative diseases in humans. Possible health beneficial effects of polyphenols are based on the human consumption and their bioavailability. Common beans (Phaseolus vulgaris L.) are a greater source of polyphenolic compounds with numerous health promoting properties. Polyphenol-rich dry common beans have potential effects on human health, and possess anti-oxidant, anti-diabetic, anti-obesity, anti-inflammatory and anti-mutagenic and anti-carcinogenic properties. Based on the studies, the current comprehensive review aims to provide up-to-date information on the nutritional compositions and health-promoting effect of polyphenol-rich common beans, which help to explore their therapeutic values for future clinical studies. Investigation of common beans and their impacts on human health were obtained from various library databases and electronic searches (Science Direct PubMed, and Google Scholar).
Fungal infections 5 The global problem of antifungal resistance: prevalence, mechanisms, and management

All serious fungal infections need appropriate antifungal therapy for successful patient outcome. Only a few classes of antifungal drugs are available, so the emergence of resistance to single drug classes and now multidrug resistance greatly hampers patient management. Azole resistance among Candida and Aspergillus species is one of the greatest challenges to clinical success, followed by echinocandin and multidrug resistance among some Candida species, especially Candida glabrata . The spread of agriculturally derived azole-resistant Aspergillus fumigatus and emerging threats such as multidrug resistant Candida auris are also alarming. The molecular mechanisms that cause drug resistance are naturally occurring in less susceptible species and are acquired in strains of susceptible organisms. Drug resistance mechanisms include altered drug-target interactions, reduced cellular drug concentrations mediated by drug efflux transporters, and permeability barriers associated with biofilms. Although C auris is inherently multidrug resistant, other strains typically develop resistance through stepwise selection of multiple drug-resistance mechanisms. Cellular stress induced by drug treatment promotes adaptation, which contributes to breakthrough resistance. Drug exposure also drives the emergence of resistance. An effective antifungal stewardship programme is essential to control drug resistance, and should incorporate rapid fungal diagnostics, therapeutic drug monitoring, and clinical intervention teams. The development of better diagnostic tools and strategies that allow targeted use of antifungals is essential to preserve drug effectiveness.
Structural Basis of Synercid® (Quinupristin-Dalfopristin) Resistance in Gram-positive Bacterial Pathogens*

Synercid®, a new semisynthetic streptogramin-derived antibiotic containing dalfopristin and quinupristin, is used in treatment of life-threatening infections caused by glycopeptide-resistant Enterococcus faecium and other bacterial pathogens. However, dissemination of genes encoding virginiamycin acetyltransferases, enzymes that confer resistance to streptogramins, threatens to limit the medical utility of the quinupristin-dalfopristin combination. Here we present structures of virginiamycin acetyltransferase D (VatD) determined at 1.8 Å resolution in the absence of ligands, at 2.8 Å resolution bound to dalfopristin, and at 3.0 Å resolution in the presence of acetyl-coenzyme A. Dalfopristin is bound by VatD in a similar conformation to that described previously for the streptogramin virginiamycin M1. However, specific interactions with the substrate are altered as a consequence of a conformational change in the pyrollidine ring that is propagated to adjacent constituents of the dalfopristin macrocycle. Inactivation of dalfopristin involves acetyl transfer from acetyl-coenzyme A to the sole (O-18) hydroxy group of the antibiotic that lies close to the side chain of the strictly conserved residue, His-82. Replacement of residue 82 by alanine is accompanied by a fall in specific activity of >105-fold, indicating that the imidazole moiety of His-82 is a major determinant of catalytic rate enhancement by VatD. The structure of the VatD-dalfopristin complex can be used to predict positions where further structural modification of the drug might preclude enzyme binding and thereby circumvent Synercid® resistance.
Analyzing user reviews in Thai language toward aspects in mobile applications

As more and more Thais own mobile devices, mobile applications are high in demand. Before installing mobile applications, many users read reviews written by other users to determine whether or not the application is worth using. In addition, mobile application developers also rely on user reviews to get insight information on which aspects of the mobile application users like or do not like and why. They can use the information to market the beloved aspects of their software product and improve on the problematic ones. However, when there are many reviews, it is difficult to comprehend information in the user reviews. Several researches in recent years aim to extract opinions and sentiments from various texts or documents such as Twitter, webboards, and software product reviews. Most of these researches are for English documents. For Thai language, researches usually focus on other contexts such as hotel reviews or general opinions on Twitter. In this paper, we present an approach to analyze user reviews written in Thai based on techniques in natural language processing, topic modeling, and sentiment analysis. The approach aims to help Thai users and developers discover dynamically, instead of pre-determined, various aspects and associated sentiments from a vast amount of user reviews. The result of the approach is a list of aspects with associated opinions and sentiments to help users assess mobile applications and provide summarized user feedbacks for developers.
Development of Primary Invasive Pneumococcal Disease Caused by Serotype 1 Pneumococci Is Driven by Early Increased Type I Interferon Response in the Lung

ABSTRACT The pneumococcus is the world's foremost respiratory pathogen, but the mechanisms allowing this pathogen to proceed from initial asymptomatic colonization to invasive disease are poorly understood. We have examined the early stages of invasive pneumococcal disease (IPD) by comparing host transcriptional responses to an invasive strain and a noninvasive strain of serotype 1 Streptococcus pneumoniae in the mouse lung. While the two strains were present in equal numbers in the lung 6 h after intranasal challenge, only the invasive strain (strain 1861) had invaded the pleural cavity at that time point; this correlated with subsequent development of bacteremia in mice challenged with strain 1861 but not the noninvasive strain (strain 1). Progression beyond the lung was associated with stronger induction of the type I interferon (IFN-I) response in the lung at 6 h. Suppression of the IFN-I response through administration of neutralizing antibody to IFNAR1 (the receptor for type I interferons) led to significantly reduced invasion of the pleural cavity by strain 1861 at 6 h postchallenge. Our data suggest that strong induction of the IFN-I response is a key factor in early progression of invasive serotype 1 strain 1861 beyond the lung during development of IPD.
Dose-response of physical activity and low back pain, osteoarthritis, and osteoporosis.

PURPOSE The purpose of this study was to examine the evidence for causal relationships between physical activity (PA) and low back pain (LBP), osteoarthritis (OA), and osteoporosis (OP), and for dose-response relations involved. METHODS Computer database searches and personal retrieval systems were used to locate relevant literature. RESULTS PA can be effective in preventing LBP (Category A) but prolonged, heavy loading can lead to LBP (Category C). Specific exercises have not been found effective in treatment of acute LBP (Category A), but PA can be effective in chronic LBP (Category B), especially for diminishing the effects of deconditioning. No evidence indicates that PA directly prevents OA. Large amounts of intensive PA involving high impacts or torsional loadings or causing injuries increases risk of OA (Category C). Light or moderate PA does not increase the risk of OA (Category C). PA can be effective in the treatment and rehabilitation of OA (Category B). High-intensity loading is osteogenic and possibly useful in prevention of OP (Category A) at the loaded site, but low to moderate loading is not osteogenic (Category D). Static efforts and slow movements are ineffective or less effective than fast application of force (Category B). The types of PA to attain the effects mentioned above are known except in the case of prevention of LBP, but dose-response relationships are poorly known; at best, semiquantitatively on the basis of just a few studies. CONCLUSION Given the shown primary and/or secondary preventative effectiveness of PA regarding LBP, OA, and OP, research to elucidate the inadequately known dose-response relations should be given high priority.