The chlamydial periplasmic stress response serine protease cHtrA is secreted into host cell cytosol

<p>Abstract</p> <p>Background</p> <p>The periplasmic High Temperature Requirement protein A (HtrA) plays important roles in bacterial protein folding and stress responses. However, the role of chlamydial HtrA (cHtrA) in chlamydial pathogenesis is not clear.</p> <p>Results</p> <p>The cHtrA was detected both inside and outside the chlamydial inclusions. The detection was specific since both polyclonal and monoclonal anti-cHtrA antibodies revealed similar intracellular labeling patterns that were only removed by absorption with cHtrA but not control fusion proteins. In a Western blot assay, the anti-cHtrA antibodies detected the endogenous cHtrA in Chlamydia-infected cells without cross-reacting with any other chlamydial or host cell antigens. Fractionation of the infected cells revealed cHtrA in the host cell cytosol fraction. The periplasmic cHtrA protein appeared to be actively secreted into host cell cytosol since no other chlamydial periplasmic proteins were detected in the host cell cytoplasm. Most chlamydial species secreted cHtrA into host cell cytosol and the secretion was not inhibitable by a type III secretion inhibitor.</p> <p>Conclusion</p> <p>Since it is hypothesized that chlamydial organisms possess a proteolysis strategy to manipulate host cell signaling pathways, secretion of the serine protease cHtrA into host cell cytosol suggests that the periplasmic cHtrA may also play an important role in chlamydial interactions with host cells.</p

Parameter-Saving Adversarial Training: Reinforcing Multi-Perturbation Robustness via Hypernetworks

Adversarial training serves as one of the most popular and effective methods to defend against adversarial perturbations. However, most defense mechanisms only consider a single type of perturbation while various attack methods might be adopted to perform stronger adversarial attacks against the deployed model in real-world scenarios, e.g., $\ell_2$ or $\ell_\infty$. Defending against various attacks can be a challenging problem since multi-perturbation adversarial training and its variants only achieve suboptimal robustness trade-offs, due to the theoretical limit to multi-perturbation robustness for a single model. Besides, it is impractical to deploy large models in some storage-efficient scenarios. To settle down these drawbacks, in this paper we propose a novel multi-perturbation adversarial training framework, parameter-saving adversarial training (PSAT), to reinforce multi-perturbation robustness with an advantageous side effect of saving parameters, which leverages hypernetworks to train specialized models against a single perturbation and aggregate these specialized models to defend against multiple perturbations. Eventually, we extensively evaluate and compare our proposed method with state-of-the-art single/multi-perturbation robust methods against various latest attack methods on different datasets, showing the robustness superiority and parameter efficiency of our proposed method, e.g., for the CIFAR-10 dataset with ResNet-50 as the backbone, PSAT saves approximately 80\% of parameters with achieving the state-of-the-art robustness trade-off accuracy.Comment: 9 pages, 2 figure

Hydraulic Transients Induced by Pigging Operation in Pipeline with a Long Slope

Pigging in pipelines basically performs operations for five reasons including cleaning the pipe interior, batching or separating dissimilar products, displacement, measurement, and internal inspection. A model has been proposed for the dynamic simulation of the pigging process after water pressure testing in a long slope pipeline. In this study, an attempt has been made to analyze two serious accidents during pigging operation in 2010 by the model which is developed by the method of characteristic (MOC) by Wylie et al. (1993) and the two-phase homogeneous equilibrium vaporous cavitation model deveoped by Shu (2003) for vaporous cavitation. Moreover, simulation results of the third operation show good agreement with field data from the previous field trial. After investigation, it was showed that the impulse pressures produced during collapse of a vapor cavity result in severe damage of tubes

Dietary Diversity and Nutrient Intake of Han and Dongxiang Smallholder Farmers in Poverty Areas of Northwest China

This study aimed to evaluate the status of dietary diversity and nutrient intake among Han and Dongxiang smallholder farmers in poor rural areas of northwest China. In this cross-sectional study, dietary intake was assessed in 499 smallholder farmers aged 18–75 years from two nationally designated impoverished counties in Gansu Province, China, using three consecutive 24 h dietary recalls. The dietary diversity score (DDS) and nutrient adequacy ratio (NAR) were adopted to assess dietary diversity and micronutrient adequacy, respectively. The mean DDS (range from 1 to 9) in participants was relatively low (3.81 ± 1.01). Consumption of grains was excessive, while consumption of vegetables, fruits, meat, beans, eggs, fish, and dairy was inadequate. The NAR values were higher in Han Chinese, with the exceptions of vitamin C, potassium, pyridoxine, and selenium (p \u3c 0.05). For each nutrient, the high DDS group had a higher mean NAR (p \u3c 0.05), except for pyridoxine. High household monthly income, being Han Chinese, high DDS, and being aged over 45 years were positively associated with mean adequacy ratio (MAR) of 14 micronutrients evaluated. Lack of dietary diversity and insufficient intake of essential micronutrients are public health concerns in northwest China. Nutrition education and other proper methods to address these issues are needed

Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

Abstract: Major depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD

Ancient Genomes Reveal the Evolutionary History and Origin of Cashmere-Producing Goats in China

Goats are one of the most widespread farmed animals across the world; however, their migration route to East Asia and local evolutionary history remain poorly understood. Here, we sequenced 27 ancient Chinese goat genomes dating from the Late Neolithic period to the Iron Age. We found close genetic affinities between ancient and modern Chinese goats, demonstrating their genetic continuity. We found that Chinese goats originated from the eastern regions around the Fertile Crescent, and we estimated that the ancestors of Chinese goats diverged from this population in the Chalcolithic period. Modern Chinese goats were divided into a northern and a southern group, coinciding with the most prominent climatic division in China, and two genes related to hair follicle development, FGF5 and EDA2R, were highly divergent between these populations. We identified a likely causal de novo deletion near FGF5 in northern Chinese goats that increased to high frequency over time, whereas EDA2R harbored standing variation dating to the Neolithic. Our findings add to our understanding of the genetic composition and local evolutionary process of Chinese goats

Seizing the window of opportunity to mitigate the impact of climate change on the health of Chinese residents

The health threats posed by climate change in China are increasing rapidly. Each province faces different health risks. Without a timely and adequate response, climate change will impact lives and livelihoods at an accelerated rate and even prevent the achievement of the Healthy and Beautiful China initiatives. The 2021 China Report of the Lancet Countdown on Health and Climate Change is the first annual update of China’s Report of the Lancet Countdown. It comprehensively assesses the impact of climate change on the health of Chinese households and the measures China has taken. Invited by the Lancet committee, Tsinghua University led the writing of the report and cooperated with 25 relevant institutions in and outside of China. The report includes 25 indicators within five major areas (climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement) and a policy brief. This 2021 China policy brief contains the most urgent and relevant indicators focusing on provincial data: The increasing health risks of climate change in China; mixed progress in responding to climate change. In 2020, the heatwave exposures per person in China increased by 4.51 d compared with the 1986–2005 average, resulting in an estimated 92% increase in heatwave-related deaths. The resulting economic cost of the estimated 14500 heatwave-related deaths in 2020 is US$176 million. Increased temperatures also caused a potential 31.5 billion h in lost work time in 2020, which is equivalent to 1.3% of the work hours of the total national workforce, with resulting economic losses estimated at 1.4% of China’s annual gross domestic product. For adaptation efforts, there has been steady progress in local adaptation planning and assessment in 2020, urban green space growth in 2020, and health emergency management in 2019. 12 of 30 provinces reported that they have completed, or were developing, provincial health adaptation plans. Urban green space, which is an important heat adaptation measure, has increased in 18 of 31 provinces in the past decade, and the capacity of China’s health emergency management increased in almost all provinces from 2018 to 2019. As a result of China’s persistent efforts to clean its energy structure and control air pollution, the premature deaths due to exposure to ambient particulate matter of 2.5 μm or less (PM2.5) and the resulting costs continue to decline. However, 98% of China’s cities still have annual average PM2.5 concentrations that are more than the WHO guideline standard of 10 μg/m3. It provides policymakers and the public with up-to-date information on China’s response to climate change and improvements in health outcomes and makes the following policy recommendations. (1) Promote systematic thinking in the related departments and strengthen multi-departmental cooperation. Sectors related to climate and development in China should incorporate health perspectives into their policymaking and actions, demonstrating WHO’s and President Xi Jinping’s so-called health-in-all-policies principle. (2) Include clear goals and timelines for climate-related health impact assessments and health adaptation plans at both the national and the regional levels in the National Climate Change Adaptation Strategy for 2035. (3) Strengthen China’s climate mitigation actions and ensure that health is included in China’s pathway to carbon neutrality. By promoting investments in zero-carbon technologies and reducing fossil fuel subsidies, the current rebounding trend in carbon emissions will be reversed and lead to a healthy, low-carbon future. (4) Increase awareness of the linkages between climate change and health at all levels. Health professionals, the academic community, and traditional and new media should raise the awareness of the public and policymakers on the important linkages between climate change and health.</p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe