Prevalence, distribution and risk factors for brucellosis infection in goat farms in Ningxiang, China

Background In south China, goats are the major source of Brucellosis for human infection. However, there are few studies on the prevalence of and risk factors for goat brucellosis in south China. In this study, we conducted a cross-sectional study to investigate the herd prevalence, spatial distribution and relevant risk factors for goat brucellosis in Ningxiang county, south China. Commercial goat farms (n = 457) were randomly selected, and their disease status was ascertained by testing serum samples of chosen individuals using the Rose Bengal Test (screening test) and the Serum Agglutination Test (confirmatory test) in series. A farm with at least two positive individuals was defined as a case farm. Standardized questionnaires were used to collect information on management and hygiene practices in farms. A logistic model with a binomial outcome was built to identify risk factors for being seropositive. Results The true herd prevalence in commercial goat farms was 4.5% (95%CI: 0.2%-12.2%) and the townships in the centre of the county had higher herd prevalence. The risk factors associated with seropositive on local goat farms include “Introduction in the past 12 months” (OR= 61, 95%CI: 16-333), “Improperly disposal of the sick or dead goats” (OR= 33, 95%CI: 5-341) and “Poor hygiene in lambing pen” (OR= 25, 95%CI: 5-192). Conclusions These findings will aid in the development of control strategies of Brucellosis in south China and risk factors identified in this study should be taken into consideration when designing a control strategy

The Magellan M2FS Spectroscopic Survey of High-Redshift Galaxies: A Sample of 260 Lyα\alpha Emitters at Redshift z≈5.7z\approx5.7

We present a spectroscopic survey of Ly$\alpha$ emitters (LAEs) at $z\approx5.7$ using the multi-object spectrograph M2FS on the Magellan Clay telescope. This is part of a high-redshift galaxy survey carried out in several well-studied deep fields. These fields have deep images in multiple UV/optical bands, including a narrow NB816 band that has allowed an efficient selection of LAE candidates at $z\approx5.7$. Our sample consists of 260 LAEs and covers a total effective area of more than two square degrees on the sky. This is so far the largest (spectroscopically confirmed) sample of LAEs at this redshift. We use the secure redshifts and narrowband photometry to measure Ly$\alpha$ luminosities. We find that these LAEs span a Ly$\alpha$ luminosity range of $\sim 2\times10^{42} - 5\times10^{43}$ erg s$^{-1}$, and include some of the most luminous galaxies known at $z \ge 5.7$ in terms of Ly$\alpha$ luminosity. Most of them have rest-frame equivalent widths between 20 and 300 \r{A}, and more luminous Ly$\alpha$ emission lines tend to have broader line widths. We detect a clear offset of $\sim20$ \r{A} between the observed Ly$\alpha$ wavelength distribution and the NB816 filter transmission curve, which can be explained by the intergalactic medium absorption of continua blueward of Ly$\alpha$ in the high-redshift spectra. This sample is being used to study the Ly$\alpha$ luminosity function and galaxy properties at $z\approx5.7$.Comment: 16 pages, 12 figures, 3 tables; Accepted for publication in Ap

Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): evaluation using an endogenous HCC model

Hepatocellular carcinoma (HCC) is a lethal malignancy with high mortality and poor prognosis. Oncogenic transcription factor Late SV40 Factor (LSF) plays an important role in promoting HCC. A small molecule inhibitor of LSF, Factor Quinolinone Inhibitor 1 (FQI1), significantly inhibited human HCC xenografts in nude mice without harming normal cells. Here we evaluated the efficacy of FQI1 and another inhibitor, FQI2, in inhibiting endogenous hepatocarcinogenesis. HCC was induced in a transgenic mouse with hepatocyte-specific overexpression of c-myc (Alb/c-myc) by injecting N-nitrosodiethylamine (DEN) followed by FQI1 or FQI2 treatment after tumor development. LSF inhibitors markedly decreased tumor burden in Alb/c-myc mice with a corresponding decrease in proliferation and angiogenesis. Interestingly, in vitro treatment of human HCC cells with LSF inhibitors resulted in mitotic arrest with an accompanying increase in CyclinB1. Inhibition of CyclinB1 induction by Cycloheximide or CDK1 activity by Roscovitine significantly prevented FQI-induced mitotic arrest. A significant induction of apoptosis was also observed upon treatment with FQI. These effects of LSF inhibition, mitotic arrest and induction of apoptosis by FQI1s provide multiple avenues by which these inhibitors eliminate HCC cells. LSF inhibitors might be highly potent and effective therapeutics for HCC either alone or in combination with currently existing therapies.The present study was supported in part by grants from The James S. McDonnell Foundation, National Cancer Institute Grant R01 CA138540-01A1 (DS), National Institutes of Health Grant R01 CA134721 (PBF), the Samuel Waxman Cancer Research Foundation (SWCRF) (DS and PBF), National Institutes of Health Grants R01 GM078240 and P50 GM67041 (SES), the Johnson and Johnson Clinical Innovation Award (UH), and the Boston University Ignition Award (UH). JLSW was supported by Alnylam Pharmaceuticals, Inc. DS is the Harrison Endowed Scholar in Cancer Research and Blick scholar. PBF holds the Thelma Newmeyer Corman Chair in Cancer Research. The authors acknowledge Dr. Lauren E. Brown (Dept. Chemistry, Boston University) for the synthesis of FQI1 and FQI2, and Lucy Flynn (Dept. Biology, Boston University) for initially identifying G2/M effects caused by FQI1. (James S. McDonnell Foundation; R01 CA138540-01A1 - National Cancer Institute; R01 CA134721 - National Institutes of Health; R01 GM078240 - National Institutes of Health; P50 GM67041 - National Institutes of Health; Samuel Waxman Cancer Research Foundation (SWCRF); Johnson and Johnson Clinical Innovation Award; Boston University Ignition Award; Alnylam Pharmaceuticals, Inc.)Published versio

Model-based analysis uncovers mutations altering autophagy selectivity in human cancer

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis

Screening of traditional Chinese medicines with therapeutic potential on chronic obstructive pulmonary disease through inhibiting oxidative stress and inflammatory response

NADP(H): quinone oxidoreductase (QR) inducing effects of 38 bioactive TCM extracts in hepa 1c1c7 cells. The QR inducing effect was determined after 24h treatment of the hepa 1c1c7 cells in the presence or absence of tested TCMs. The data of the untreated control group was normalized as 1, and then the QR inducing activity of tested extracts was represented by the maximum folds of QR inducing activity (MQI) compared with the untreated control group. Sulforaphane (SF, 2.0 μM) was used as a positive control. The data are reported the means ± SD from three independent experiments. Figure S2. Inhibitory effects on NO production of 55 bioactive TCM extracts in RAW 264.7 cells. The NO concentration in the RAW 264.7 cell culture media was determined through the Griess reaction 24 h after treated in the presence or absence of tested TCMs and lipopolysaccharides (LPS, 1.0 μg/mL). Didox (100 μM) was adopted as a positive control. The data are reported the means ± SD from three independent experiments. The maximum inhibition rates (MIRs) of NO production under the untoxic tested concentration were calculated by comparing the decreased NO concentration in TCM-treated group with that in LPS-stimulated group. Table S1. TCM extracts with QR inducing activity and/or NO inhibitory effect. (DOCX 4312 kb

A possible 250-second X-ray quasi-periodicity in the fast blue optical transient AT2018cow

The fast blue optical transients (FBOTs) are a new population of extragalactic transients of unclear physical origin. A variety of mechanisms have been proposed including failed supernova explosion, shock interaction with a dense medium, young magnetar, accretion onto a compact object, and stellar tidal disruption event, but none is conclusive. Here we report the discovery of a possible X-ray quasi-periodicity signal with a period of $\sim$250 second (at a significance level of 99.76%) in the brightest FBOT AT2018cow through the analysis of XMM-Newton/PN data. The signal is independently detected at the same frequency in the average power density spectrum from data taken from the Swift telescope, with observations covering from 6 to 37 days after the optical discovery, though the significance level is lower (94.26%). This suggests that the QPO frequency may be stable over at least 1.1$\times$ 10$^{4}$ cycles. Assuming the $\sim$250 second QPO to be a scaled-down analogue of that typically seen in stellar mass black holes, a black hole mass of $\sim10^{3}-10^{5}$ solar masses could be inferred. The overall X-ray luminosity evolution could be modeled with the stellar tidal disruption by a black hole of $\sim10^4$ solar masses, providing a viable mechanism to produce AT2018cow. Our findings suggest that other bright FBOTs may also harbor intermediate-mass black holes.Comment: 18 pages, 10 figures. Accepted for publication in Research in Astronomy and Astrophysic

A case-control study on risk factors of breast cancer in China

Introduction: To screen the risk factors associated with breast cancer among Chinese women in order to evaluate the individual risk of developing breast cancer among women in China. Material and methods: A case-control study on 416 breast cancer patients and 1156 matched controls was conducted in 14 hospitals in 8 provinces of China in 2008. Controls were age- and region-matched to the cases. Clinicians conducted in-person interviews with the subjects to collect information on demographics and suspected risk factors for breast cancer that are known worldwide. Conditional logistic regression was used to derive odds ratios (OR) and 95% confidence intervals (CI) for the associations between risk factors and breast cancer. Results: Compared with matched controls, women with breast cancer were significantly more likely to have higher body mass index (BMI, OR = 4.07, 95% CI; 2.98-5.55), history of benign breast disease (BBD) biopsy (OR = 1.68, 95% CI; 1.19-2.38), older age of menarche (AOM) (OR = 1.41, 95% CI: 107-187), stress anticipation (SA), for grade 1-4, OR = 2.15, 95% CI; 1.26-3.66; for grade 5-9, OR = 3.48, 95% CI; 2.03-5.95) and menopause (OR = 2.22, 95% CI: 1.50-3.282) at the level of p < 0.05. Family history of breast cancer (FHBC) in first-degree relatives (OR = 1.66, 95% CI; 0.77-3.59) and use of oral contraceptives (OC) (OR = 1.59, 95% CI; 0.83-3.05) were associated with an increased risk of breast cancer at the level of p < 0.20. Conclusions: Our results showed that BMI, history of BBD biopsy, older AOM, SA and menopause were associated with increased risk of breast cancer among Chinese women. The findings derived from the study provided some suggestions for population-based prevention and control of breast cancer in China.Medicine, General & InternalSCI(E)15ARTICLE2303-309

Clinical and biomarker trajectories in sporadic Alzheimer's disease: A longitudinal study.

Introduction: Amyloid beta (Aβ) deposition was identified to precede tau pathology and neurodegeneration in familial Alzheimer's disease (AD). But the divergence between sporadic and familial AD limits the extension of these findings to sporadic AD. Methods: Longitudinal changes of biomarkers among different stages were assessed using linear mixed-effects models. The slopes of the models were used to estimate rates of change to calculate the biomarker trajectories in sporadic AD. Results: Cerebrospinal fluid (CSF) Aβ was estimated to decline 45.2 years (abnormal: 27.8 years) before dementia, and Aβ deposition seemed to increase 31.7 years (abnormal: 26.7 years) before dementia. It was estimated to take 29.0 years (CSF t-tau), 12.2 years (memory), 11.6 years (hippocampus), 9.3 years (hypometabolism), and 6.1 years (cognition) to move from normal to dementia. Discussion: The trajectory in sporadic AD is led by Aβ accumulation, followed by CSF t-tau increase, memory deficits, brain atrophy, hypometabolism, and cognitive decline