A Comparison of Computational Methods for Identifying Virulence Factors

Bacterial pathogens continue to threaten public health worldwide today. Identification of bacterial virulence factors can help to find novel drug/vaccine targets against pathogenicity. It can also help to reveal the mechanisms of the related diseases at the molecular level. With the explosive growth in protein sequences generated in the postgenomic age, it is highly desired to develop computational methods for rapidly and effectively identifying virulence factors according to their sequence information alone. In this study, based on the protein-protein interaction networks from the STRING database, a novel network-based method was proposed for identifying the virulence factors in the proteomes of UPEC 536, UPEC CFT073, P. aeruginosa PAO1, L. pneumophila Philadelphia 1, C. jejuni NCTC 11168 and M. tuberculosis H37Rv. Evaluated on the same benchmark datasets derived from the aforementioned species, the identification accuracies achieved by the network-based method were around 0.9, significantly higher than those by the sequence-based methods such as BLAST, feature selection and VirulentPred. Further analysis showed that the functional associations such as the gene neighborhood and co-occurrence were the primary associations between these virulence factors in the STRING database. The high success rates indicate that the network-based method is quite promising. The novel approach holds high potential for identifying virulence factors in many other various organisms as well because it can be easily extended to identify the virulence factors in many other bacterial species, as long as the relevant significant statistical data are available for them

Induction and Suppression of Innate Antiviral Responses by Hepatitis A Virus

Hepatitis A virus (HAV) belongs to the family Picornaviridae. It is the pathogen of acute viral hepatitis caused by fecal-oral transmission. RNA viruses are sensed by pathogen-associated pattern recognition receptors (PRRs) such as Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I), and melanoma differentiation-associated gene 5 (MDA5). PRR activation leads to production of type 1 interferon (IFN-α/β), serving as the first line of defense against viruses. However, HAV has developed various strategies to compromise the innate immune system and promote viral propagation within the host cells. The long coevolution of HAV in hosts has prompted the development of effective immune antagonism strategies that actively fight against host antiviral responses. Proteases encoded by HAV can cleave the mitochondrial antiviral signaling protein (MAVS, also known as IPS-1, VISA, or Cardif), TIR domain- containing adaptor inducing IFN-β (TRIF, also known as TICAM-1) and nuclear factor-κB (NF-κB) essential modulator (NEMO), which are key adaptor proteins in RIG-I-like receptor (RLR), TLR3 and NF-κB signaling, respectively. In this mini-review, we summarize all the recent progress on the interaction between HAV and the host, especially focusing on how HAV abrogates the antiviral effects of the innate immune system

Toolpath interpolation and smoothing for computer numerical control machining of freeform surfaces : a review

Driven by the ever increasing demand in function integration, more and more next generation high value-added products, such as head-up displays, solar concentrators and intra-ocular-lens, etc., are designed to possess freeform (i.e., non-rotational symmetric) surfaces. The toolpath, composed of high density of short linear and circular segments, is generally used in computer numerical control (CNC) systems to machine those products. However, the discontinuity between toolpath segments leads to high-frequency fluctuation of feedrate and acceleration, which will decrease the machining efficiency and product surface finish. Driven by the ever-increasing need for high-speed high-precision machining of those products, many novel toolpath interpolation and smoothing approaches have been proposed in both academia and industry, aiming to alleviate the issues caused by the conventional toolpath representation and interpolation methods. This paper provides a comprehensive review of the state-of-the-art toolpath interpolation and smoothing approaches with systematic classifications. The advantages and disadvantages of these approaches are discussed. Possible future research directions are also offered

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

The Minimum Variation Timescales of X-ray bursts from SGR J1935+2154

The minimum variation timescale (MVT) of soft gamma-ray repeaters can be an important probe to estimate the emission region in pulsar-like models, as well as the Lorentz factor and radius of the possible relativistic jet in gamma-ray burst (GRB)-like models, thus revealing their progenitors and physical mechanisms. In this work, we systematically study the MVTs of hundreds of X-ray bursts (XRBs) from SGR J1935+2154 observed by {\it Insight}-HXMT, GECAM and Fermi/GBM from July 2014 to Jan 2022 through the Bayesian Block algorithm. We find that the MVTs peak at $\sim$ 2 ms, corresponding to a light travel time size of about 600 km, which supports the magnetospheric origin in pulsar-like models. The shock radius and the Lorentz factor of the jet are also constrained in GRB-like models. Interestingly, the MVT of the XRB associated with FRB 200428 is $\sim$ 70 ms, which is longer than that of most bursts and implies its special radiation mechanism. Besides, the median of MVTs is 7 ms, shorter than the median MVTs of 40 ms and 480 ms for short GRBs or long GRBs, respectively. However, the MVT is independent of duration, similar to GRBs. Finally, we investigate the energy dependence of MVT and suggest that there is a marginal evidence for a power-law relationship like GRBs but the rate of variation is at least about an order of magnitude smaller. These features may provide an approach to identify bursts with a magnetar origin.Comment: accepted for publication in ApJ