iAssembler: a package for de novo assembly of Roche-454/Sanger transcriptome sequences

<p>Abstract</p> <p>Background</p> <p>Expressed Sequence Tags (ESTs) have played significant roles in gene discovery and gene functional analysis, especially for non-model organisms. For organisms with no full genome sequences available, ESTs are normally assembled into longer consensus sequences for further downstream analysis. However current <it>de novo </it>EST assembly programs often generate large number of assembly errors that will negatively affect the downstream analysis. In order to generate more accurate consensus sequences from ESTs, tools are needed to reduce or eliminate errors from <it>de novo </it>assemblies.</p> <p>Results</p> <p>We present iAssembler, a pipeline that can assemble large-scale ESTs into consensus sequences with significantly higher accuracy than current existing assemblers. iAssembler employs MIRA and CAP3 assemblers to generate initial assemblies, followed by identifying and correcting two common types of transcriptome assembly errors: 1) ESTs from different transcripts (mainly alternatively spliced transcripts or paralogs) are incorrectly assembled into same contigs; and 2) ESTs from same transcripts fail to be assembled together. iAssembler can be used to assemble ESTs generated using the traditional Sanger method and/or the Roche-454 massive parallel pyrosequencing technology.</p> <p>Conclusion</p> <p>We compared performances of iAssembler and several other <it>de novo </it>EST assembly programs using both Roche-454 and Sanger EST datasets. It demonstrated that iAssembler generated significantly more accurate consensus sequences than other assembly programs.</p

The Right of Deduction within the European VAT: A Perspective for the VAT Reform in China

Value added tax (VAT), with its specific and unique feature as a neutral taxation, has spread rapidly around the world since its first adoption in Europe. China has also chosen to adopt VAT in an attempt to promote its economic development. In 2012, China started a new round of reform of VAT to extend its scope to industries which previously were liable to business tax. One of the most difficult problems is the rebuilding of the VAT deduction system therein. Although Europe faces its own problems and difficulties in the process of perfection and coordination of VAT, as the cradle of VAT it could still provide helpful insights for the ongoing VAT reform in China. Based on the analysis of the VAT system and, in particular, the right to deduct input VAT in Europe, combined with the development and special conditions of VAT in China, I propose several recommendations for the ongoing VAT reform in China and its future legislation. First, on the overall level, it is important to review the principle of neutrality in VAT, and rather than to view it as a natural result of the operation of the VAT system, its role as a rule to be complied with. Second, with regard to the design of the VAT deduction system, I argue that: (1) it is not necessary to establish VAT deduction as a substantive right of the taxpayer; (2) it is necessary to expand the scope of deductible items in China, especially in relation to fixed capital investment; (3) it is urgent to improve the treatment of the excess amount of deductible input VAT. Finally, suggestions are given supporting the construction of the related procedural legislation

ViP-Mixer: A Convolutional Mixer for Video Prediction

Video prediction aims to predict future frames from a video's previous content. Existing methods mainly process video data where the time dimension mingles with the space and channel dimensions from three distinct angles: as a sequence of individual frames, as a 3D volume in spatiotemporal coordinates, or as a stacked image where frames are treated as separate channels. Most of them generally focus on one of these perspectives and may fail to fully exploit the relationships across different dimensions. To address this issue, this paper introduces a convolutional mixer for video prediction, termed ViP-Mixer, to model the spatiotemporal evolution in the latent space of an autoencoder. The ViP-Mixers are stacked sequentially and interleave feature mixing at three levels: frames, channels, and locations. Extensive experiments demonstrate that our proposed method achieves new state-of-the-art prediction performance on three benchmark video datasets covering both synthetic and real-world scenarios.Comment: Under revie

Expansion of Myeloid-Derived Suppressor Cells Promotes Differentiation of Regulatory T Cells in HIV-1+ Individuals

Objective: Regulatory T cells (Tregs) contribute to HIV-1 disease progression by impairing antiviral immunity; however, the precise mechanisms responsible for the development of Tregs in the setting of HIV-1 infection are incompletely understood. Design: In this study, we provide evidence that HIV-induced expansion of monocytic myeloid-derived suppressor cells (M-MDSCs) promote the differentiation of Foxp3+ Tregs. Methods: We measured MDSC induction and cytokine expression by flow cytometry and analyzed their functions by coculturing experiments. Results: We observed a dramatic increase in M-MDSC frequencies in the peripheral blood of HIV-1 seropositive (HIV-1+) individuals, even in those on antiretroviral therapy with undetectable viremia, when compared with healthy participants. We also observed increases in M-MDSCs after incubating healthy peripheral mononuclear cells (PBMCs) with HIV-1 proteins (gp120 or Tat) or Toll-like receptor 4 ligand lipopolysaccharides in vitro, an effect that could be abrogated in the presence of the phosphorylated signal transducer and activator of transcription 3 inhibitor, STA-21. Functional analyses indicated that M-MDSCs from HIV-1+ individuals express higher levels of IL-10, tumor growth factor-β, IL-4 receptor α, p47phex, programmed death-ligand 1, and phosphorylated signal transducer and activator of transcription 3 – all of which are known mediators of myelopoiesis and immunosuppression. Importantly, incubation of healthy CD4+ T cells with MDSCs derived from HIV-1+ individuals significantly increased differentiation of Foxp3+ Tregs. In addition, depletion of MDSCs from PBMCs of HIV-1+ individuals led to a significant reduction of Foxp3+ Tregs and increase of IFNγ production by CD4+ T effector cells. Conclusions: These results suggest that HIV-induced MDSCs promote Treg cell development and inhibit T cell function – a hallmark of many chronic infectious diseases

Normal Values of Myocardial Deformation Assessed by Cardiovascular Magnetic Resonance Feature Tracking in a Healthy Chinese Population: A Multicenter Study

Reference values on atrial and ventricular strain from cardiovascular magnetic resonance (CMR) are essential in identifying patients with impaired atrial and ventricular function. However, reference values have not been established for Chinese subjects. One hundred and fifty healthy volunteers (75 Males/75 Females; 18–82 years) were recruited. All underwent CMR scans with images acceptable for further strain analysis. Subjects were stratified by age: Group 1, 18–44 years; Group 2, 45–59 years; Group 3, ≥60 years. Feature tracking of CMR cine imaging was used to obtain left atrial global longitudinal (LA Ell) and circumferential strains (LA Ecc) and respective systolic strain rates, left ventricular longitudinal (LV Ell), circumferential (LV Ecc) and radial strains (LV Err) and their respective strain rates, and right ventricular longitudinal strain (RV Ell) and strain rate. LA Ell and LA Ecc were 32.8 ± 9.2% and 40.3 ± 13.4%, respectively, and RV Ell was −29.3 ± 6.0%. LV Ell, LV Ecc and LV Err were −22.4 ± 2.9%, −24.3 ± 3.1%, and 79.0 ± 19.4%, respectively. LV Ell and LV Ecc were higher in females than males (P &lt; 0.05). LA Ell, LA Ecc, and LV Ecc decreased, while LV Err increased with age (P &lt; 0.05). LV Ell and RV Ell were not shown to be associated with age. Normal ranges for atrial and ventricular strain and strain rates are provided using CMR feature tracking in Chinese subjects

Low Mannose Binding Lectin, but Not L-Ficolin, Is Associated With Spontaneous Clearance of Hepatitis C Virus After Infection

Some individuals can spontaneously clear the hepatitis C virus (HCV) after infection, whereas others develop a chronic infection. The exact mechanism of this phenomenon is unknown. We aimed to evaluate the association of plasma levels of MBL, L-ficolin, and cytokines with outcome of HCV infections in two groups of patients who cleared HCV spontaneously (CHS), and who developed chronic HCV infections (CHC). Altogether, 86 patients and 183 healthy controls were included. Of 86 patients, 36 had CHS and 50 had CHC. Concentrations of plasma MBL and L-ficolin were measured in patients and controls. Twenty plasma cytokines and adhesion molecules, including GM-CSF, ICAM-1, IFN-gamma, IFN-alpha, IL-1 alpha, IL-1 beta, IL-10, IL-12p70, IL-13, IL-17A, IL-4, IL-8, IP-10, MCP-1, IL-6, MIP-1 alpha, MIP-1 beta, sE-Selectin, sP-Selectin, and TNF-alpha, were determined in all patients and randomly selected 45 controls. The level of MBL was significantly lower in subjects with CHS than in healthy controls (median: 293.10 vs. 482.64 ng/ml, p = 0.008), whereas the level of MBL was significantly higher in patients with CHC than in controls (median: 681.32 vs. 482.64 ng/ml, p = 0.001). No such differences in plasma L-ficolin were observed. Plasma levels of all cytokines and adhesion molecules, except ICAM-1, were significantly higher in patients than in controls. Moreover, patients with CHC had significantly higher levels of IFN-gamma, IFN-alpha, IL-1 alpha, IL-10, IL-13, IL-4, IL-6, and TNF-alpha than those with CHS. These findings implicate that lower levels of plasma MBL, together with lower levels of above mentioned cytokines may play a part in virus clearance of HCV infection

Monitoring Water and Energy Cycles at Climate Scale in the Third Pole Environment (CLIMATE-TPE)

A better understanding of the water and energy cycles at climate scale in the Third Pole Environment is essential for assessing and understanding the causes of changes in the cryosphere and hydrosphere in relation to changes of plateau atmosphere in the Asian monsoon system and for predicting the possible changes in water resources in South and East Asia. This paper reports the following results: (1) A platform of in situ observation stations is briefly described for quantifying the interactions in hydrosphere-pedosphere-atmosphere-cryosphere-biosphere over the Tibetan Plateau. (2) A multiyear in situ L-Band microwave radiometry of land surface processes is used to develop a new microwave radiative transfer modeling system. This new system improves the modeling of brightness temperature in both horizontal and vertical polarization. (3) A multiyear (2001–2018) monthly terrestrial actual evapotranspiration and its spatial distribution on the Tibetan Plateau is generated using the surface energy balance system (SEBS) forced by a combination of meteorological and satellite data. (4) A comparison of four large scale soil moisture products to in situ measurements is presented. (5) The trajectory of water vapor transport in the canyon area of Southeast Tibet in different seasons is analyzed, and (6) the vertical water vapor exchange between the upper troposphere and the lower stratosphere in different seasons is presented

Antibiotic-Induced Disruption of Gut Microbiota Alters Local Metabolomes and Immune Responses

Gut microbiome plays an essential role in modulating host immune responses. However, little is known about the interaction of microbiota, their metabolites and relevant inflammatory responses in the gut. By treating the mice with three different antibiotics (enrofloxacin, vancomycin, and polymixin B sulfate), we aimed to investigate the effects of different antibiotics exposure on gut microbiota, microbial metabolism, inflammation responses in the gut, and most importantly, pinpoint the underlying interactions between them. Although the administration of different antibiotics can lead to different effects on mouse models, the treatment did not affect the average body weight of the mice. A heavier caecum was observed in vancomycin treated mice. Treatment by these three antibiotics significantly up-regulated gene expression of various cytokines in the colon. Enrofloxacin treated mice seemed to have an increased Th1 response in the colon. However, such a difference was not found in mice treated by vancomycin or polymixin B sulfate. Vancomycin treatment induced significant changes in bacterial composition at phylum and family level and decreased richness and diversity at species level. Enrofloxacin treatment only induced changes in composition at family presenting as an increase in Prevotellaceae and Rikenellaceae and a decrease in Bacteroidaceae. However, no significant difference was observed after polymixin B sulfate treatment. When compared with the control group, significant metabolic shift was found in the enrofloxacin and vancomycin treated group. The metabolic changes mainly occurred in Valine, leucine, and isoleucine biosynthesis pathway and beta-Alanine metabolism in enrofloxacin treated group. For vancomycin treatment metabolic changes were mainly found in beta-Alanine metabolism and Alanine, aspartate and glutamate metabolism pathway. Moreover, modifications observed in the microbiota compositions were correlated with the metabolite concentrations. For example, concentration of pentadecanoic acid was positively correlated with richness of Rikenellaceae and Prevotellaceae and negatively correlated with Enterobacteriaceae. This study suggests that the antibiotic-induced changes in gut microbiota might contribute to the inflammation responses through the alternation of metabolic status, providing a novel insight regarding a complex network that integrates the different interactions between gut microbiota, metabolic functions, and immune responses in host

The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules are associated with primary Sjögren's syndrome

在这篇论文当中，郑俊峰博士领导的课题小组发现在人白细胞抗原二类基因（HLA-II）中，HLA-DRB1*0803是中国南方原发干燥综合征易感基因。进一步通过结构生物信息学模拟DRB1*0803 分子结构并分析，发现HLA的抗原肽结合槽口袋9的表面电势的不同，可能是疾病易感性差异的分子基础。自身免疫病是由遗传因素和环境因素共同导致的疾病，在遗传因素里，HLA位点是很多自身免疫病的主要易感基因。但是，尽管HLA和自身免疫病的相关性非常明确，这种相关背后的机理还不清楚。这项关于HLA和干燥综合征相关性的研究在这一问题上做出了探索性的发现，对HLA和干燥综合征的相关的机制提出了新的观点。该成果也是自身免疫学实验室在干燥综合征方向上陆续发表的第4篇学术论文。Primary Sjögren's syndrome (pSS) is associated with HLA-DRB1 loci, but the association of amino acid variations in the hypervariable region of the HLA-DR β1 chain with pSS is largely unknown. In this study, we aimed to identify the amino acid variations within the hypervariable region of HLA-DRB1 molecule which are associated with the susceptibility to pSS. We sequenced the 2nd exon of the HLA-DRB1 locus in 52 pSS patients and 179 controls. The HLA-DRB1*0803 is the allele that shows the strongest association with pSS in Chinese population (OR = 3.0, P = 2.4 × 10 −4 ). Furthermore, amino acid variations within the binding pocket P7 and P9 are associated with the susceptibility to pSS. An interaction between two residues within P7, β47 and β67, is associated with pSS. Structural modeling studies demonstrated that the electrostatics of peptide binding pocket 9 are opposite in pSS-susceptible and -protective HLA-DRB1 alleles. In conclusion, our results suggest that structural heterogeneity of the HLA-DRB1 peptide binding pocket P7 and P9 might play a role in the pathogenesis of pSS

Gene Expression Profiling of Lacrimal Glands Identifies the Ectopic Expression of MHC II on Glandular Cells as a Presymptomatic Feature in a Mouse Model of Primary Sjögren's Syndrome

Ectopic expression of MHC II molecules on glandular cells is a feature of primary Sjögren's syndrome (pSS). However, the cause of this ectopic expression and its potential role in the pathogenesis of the disease remains elusive. Here, we report that ectopic expression of MHC II molecules on glandular cells represents an early presymptomatic event in a mouse model of pSS induced by immunization of Ro60_316-335 peptide emulsified in TiterMax® as an adjuvant. Ectopic expression of MHC II was induced by TiterMax® but not by complete freund's adjuvant (CFA). Furthermore, immunization with Ro60_316-335 peptide emulsified in TiterMax®, but not in CFA, induced a pSS-like disease in mice. Our results suggests that ectopic expression of MHC II molecules on glandular cells represents a presymptomatic feature of pSS and that such ectopic expression can be induced by exogenous factors. In addition, this study also provides a novel mechanism how adjuvants can amplify immune responses