Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy.

Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) checkpoint blockade immunotherapy elicits durable antitumor effects in multiple cancers, yet not all patients respond. We report the evaluation of >300 patient samples across 22 tumor types from four KEYNOTE clinical trials. Tumor mutational burden (TMB) and a T cell-inflamed gene expression profile (GEP) exhibited joint predictive utility in identifying responders and nonresponders to the PD-1 antibody pembrolizumab.

Paenibacillus assamensis in Joint Fluid of Man with Suspected Tularemia, China.

Paenibacillus assamensis is a bacterium usually found in warm springs. We detected P. assamensis in a man with suspected tularemia.

Flame-retardant effect and mechanism of melamine phosphate on silicone thermoplastic elastomer.

Different from the traditional silicone materials, which are not easily ignited, silicone thermoplastic elastomer (Si-TPE) has poor flame retardant properties due to the existence of the hard segments in its molecular chains. In this paper, melamine phosphate (MP), a kind of halogen free flame retardant, was adopted to improve the flame retardancy of Si-TPE. The results showed that MP played the role of flame retardant in both gas and condensed phases due to its nitrogen-phosphorus-containing structure.

Assessment of usefulness of synchrotron radiation techniques to determine arsenic species in hair and rice grain samples.

The arseniasis in Southwest Guizhou, China has been identified as a unique case of endemic arseniasis caused by exposure to indoor combustion of high As-content coal. Present investigation targeted the microdistribution and speciation of the element arsenic in human hair and environmental samples collected in one of the hyper-endemic villages of arseniasis in the area. Analyses were performed by micro-beam X-ray fluorescence (μ-XRF) and X-ray absorption fine structure (XAFS).

Species specific exome probes reveal new insights in positively selected genes in nonhuman primates.

Nonhuman primates (NHP) are important biomedical animal models for the study of human disease. Of these, the most widely used models in biomedical research currently are from the genus Macaca. However, evolutionary genetic divergence between human and NHP species makes human-based probes inefficient for the capture of genomic regions of NHP for sequencing and study.

[In utero exposure to di-n-butyl phthalate induces testicular cell apoptosis and vacuolization in the pubertal male rat offspring].

Objective: To investigate the impact of in utero exposure to di-n-butyl phthalate (DBP) on the apoptosis of testicular cells in the pubertal male rat offspring.

Methods: Ten pregnant SD rats were randomly divided into a control and an experimental group to be treated intragastrically with olive oil (1 ml per day) and DBP (500 mg per kg of body weight per day) respectively between gestation days 12 and 19. At the pubertal age (postnatal day 45, PND 45), the testes of the male rat offspring were removed for observation of the cell structure under the transmission electron microscope and the development of different spermatogenetic cells by HE staining.

Vimentin-Mediated Steroidogenesis Induced by Phthalate Esters: Involvement of DNA Demethylation and Nuclear Factor κB.

Di-n-butyl phthalate (DBP) and its active metabolite, monobutyl phthalate (MBP) are the most common endocrine disrupting chemicals. Many studies indicate that high-doses of DBP and/or MBP exhibit toxicity on testicular function, however, little attention have been paid to the effects of low levels of DBP/MBP on steroidogenesis. As we all know, the steroidogenic acute regulatory protein (StAR) is a key regulator involved in the steroidogenesis.

miRNA-200c mediates mono-butyl phthalate-disrupted steroidogenesis by targeting vimentin in Leydig tumor cells and murine adrenocortical tumor cells.

The reproductive toxicity of plasticizer di-n-butyl phthalate (DBP) and its active metabolite monobutyl phthalate (MBP) has been demonstrated in rodents. The objective of this study was to explore roles of vimentin and miRNA-200c in steroidogenesis interfered by MBP. Mouse Leydig tumor cells (MLTC-1) and murine adrenocortical tumor cells (Y1) were employed and exposed to various levels of MBP (10(-7), 10(-6), 10(-5) and 10(-4)M).

Predicting functional alternative splicing by measuring RNA selection pressure from multigenome alignments.

High-throughput methods such as EST sequencing, microarrays and deep sequencing have identified large numbers of alternative splicing (AS) events, but studies have shown that only a subset of these may be functional. Here we report a sensitive bioinformatics approach that identifies exons with evidence of a strong RNA selection pressure ratio (RSPR)--i.e.

Factors impacting on the excess arseniasis prevalence due to indoor combustion of high arsenic coal in a hyperendemic village.

Background: A few villages in Southwest Guizhou, China represented a unique case of arseniasis due to indoor combustion of high arsenic-content coal. The present study is aimed to analyze the contribution of possible factors or of their combination to excess prevalence of arseniasis in the exposed population.

Methods: An epidemiological investigation was conducted in all the members of three large ethnic, patrilineal clans in one of the hyperendemic villages (702 residents in 178 families, including 408 Han and 294 Hmong) where farmers of different ethnic origin have been living together in the same village for generations.

Association of XPD/ERCC2 G23591A and A35931C polymorphisms with skin lesion prevalence in a multiethnic, arseniasis-hyperendemic village exposed to indoor combustion of high arsenic coal.

More than 2,000 arsenic-related skin lesions (as at 2002) in a few villages of China's Southwest Guizhou Autonomous Prefecture represent a unique case of endemic arseniasis related with indoor combustion of high-arsenic coal. The skin lesion prevalence was significantly higher in ethnic Han villagers than in ethnic Hmong villagers. This study was focused on a possible involvement of XPD/ERCC2 G23591A and A35931C polymorphisms in risk modulation of skin lesions and in the body burden of As in this unique case of As exposure.

A follow-up study of mortality among the arseniasis patients exposed to indoor combustion of high arsenic coal in Southwest Guizhou Autonomous Prefecture, China.

Objective: This study was directed to ascertain the mortality of a group of arseniasis patients in an endemic rural township in Southwest China, where the residents were exposed for decades to indoor combustion of high arsenic coal.

Methods: All the diagnosed arseniasis cases registered in 1991 were defined as the target population, which were assigned to three symptom subgroups by the severity of dermal lesions. The death cases were surveyed and checked.

Glutathione S-transferases M1 and T1 polymorphisms and arsenic content in hair and urine in two ethnic clans exposed to indoor combustion of high arsenic coal in Southwest Guizhou, China.

A total of 2,402 cases of arsenic-related skin lesions (as of 2002) in a few villages of China's Southwest Guizhou Autonomous Prefecture represent a unique case of endemic arseniasis related with indoor combustion of high arsenic coal. A significant difference of skin lesion prevalence was observed between two clans of different ethnicities (Hmong and Han) in one of the hyperendemic villages in this prefecture. This study was focused on a possible involvement of GST T1 and M1 polymorphisms in risk modulation of skin lesions and in the body burden of As in this unique case of As exposure.

Arsenic-related skin lesions and glutathione S-transferase P1 A1578G (Ile105Val) polymorphism in two ethnic clans exposed to indoor combustion of high arsenic coal in one village.

Objectives: A total of 2402 patients with arsenic-related skin lesions, such as hyperkeratosis, hyperpigmentation or hypopigmentation, or even skin cancer in a few villages in Southwest Guizhou Autonomous Prefecture, China represent a unique case of endemic arsenism related with indoor combustion of high arsenic coal. This study aimed to investigate the cluster of arsenism cases and the possible relevant factors including GSTP1 polymorphism in two clans of different ethnic origin living in one village for generations.

Methods: A questionnaire-based study was performed in 170 Miao clan P members, 10 of whom had arsenic-related skin diseases, and 153 Han clan G1 members, 50 of whom had arsenic-related skin diseases.

Dynamic changes in subgraph preference profiles of crucial transcription factors.

Transcription factors with a large number of target genes--transcription hub(s), or THub(s)--are usually crucial components of the regulatory system of a cell, and the different patterns through which they transfer the transcriptional signal to downstream cascades are of great interest. By profiling normalized abundances (A(N)) of basic regulatory patterns of individual THubs in the yeast Saccharomyces cerevisiae transcriptional regulation network under five different cellular states and environmental conditions, we have investigated their preferences for different basic regulatory patterns. Subgraph-normalized abundances downstream of individual THubs often differ significantly from that of the network as a whole, and conversely, certain over-represented subgraphs are not preferred by any THub.

Integrated analysis of multiple data sources reveals modular structure of biological networks.

It has been a challenging task to integrate high-throughput data into investigations of the systematic and dynamic organization of biological networks. Here, we presented a simple hierarchical clustering algorithm that goes a long way to achieve this aim. Our method effectively reveals the modular structure of the yeast protein-protein interaction network and distinguishes protein complexes from functional modules by integrating high-throughput protein-protein interaction data with the added subcellular localization and expression profile data.

Phylophenetic properties of metabolic pathway topologies as revealed by global analysis.

Background: As phenotypic features derived from heritable characters, the topologies of metabolic pathways contain both phylogenetic and phenetic components. In the post-genomic era, it is possible to measure the "phylophenetic" contents of different pathways topologies from a global perspective.

Results: We reconstructed phylophenetic trees for all available metabolic pathways based on topological similarities, and compared them to the corresponding 16S rRNA-based trees.

Identifying Hfq-binding small RNA targets in Escherichia coli.

The Hfq-binding small RNAs (sRNAs) have recently drawn much attention as regulators of translation in Escherichia coli. We attempt to identify the targets of this class of sRNAs in genome scale and gain further insight into the complexity of translational regulation induced by Hfq-binding sRNAs. Using a new alignment algorithm, most known negatively regulated targets of Hfq-binding sRNAs were identified.

Faster and more accurate global protein function assignment from protein interaction networks using the MFGO algorithm.

Motivation: Predicting protein function accurately is an important issue in the post-genomic era. To achieve this goal, several approaches have been proposed deduce the function of unclassified proteins through sequence similarity, co-expression profiles, and other information. Among these methods, the global optimization method (GOM) is an interesting and powerful tool that assigns functions to unclassified proteins based on their positions in a physical interactions network [Vazquez, A.

NPInter: the noncoding RNAs and protein related biomacromolecules interaction database.

The noncoding RNAs and protein related biomacromolecules interaction database (NPInter; http://bioinfo.ibp.ac.

Genome-wide analysis of mammalian DNA segment fusion/fission.

As a powerful tool for gene function prediction, gene fusion has been widely studied in prokaryotes and certain groups of eukaryotes, but it has been little applied in studies of mammalian genomes. With the first fully sequenced mammalian genomes (human, mouse, rat) now available, we defined and collected a set of fusion/fission event-linked segments (FFLS) based on structured organized genomic alignment. The statistics of the sequence features highlighted the FFLSs against their random context.

The interactome as a tree--an attempt to visualize the protein-protein interaction network in yeast.

The refinement and high-throughput of protein interaction detection methods offer us a protein-protein interaction network in yeast. The challenge coming along with the network is to find better ways to make it accessible for biological investigation. Visualization would be helpful for extraction of meaningful biological information from the network.

Date of origin of the SARS coronavirus strains.

Background: A new respiratory infectious epidemic, severe acute respiratory syndrome (SARS), broke out and spread throughout the world. By now the putative pathogen of SARS has been identified as a new coronavirus, a single positive-strand RNA virus. RNA viruses commonly have a high rate of genetic mutation.

Topological structure analysis of the protein-protein interaction network in budding yeast.

Interaction detection methods have led to the discovery of thousands of interactions between proteins, and discerning relevance within large-scale data sets is important to present-day biology. Here, a spectral method derived from graph theory was introduced to uncover hidden topological structures (i.e.

Phylogeny of SARS-CoV as inferred from complete genome comparison.

SARS-CoV, as the pathogeny of severe acute respiratory syndrome (SARS), is a mystery that the origin of the virus is still unknown even a few isolates of the virus were completely sequenced. To explore the genesis of SARS-CoV, the FDOD method previously developed by us was applied to comparing complete genomes from 12 SARS-CoV isolates to those from 12 previously identified coronaviruses and an unrooted phylogenetic tree was constructed. Our results show that all SARS-CoV isolates were clustered into a clique and previously identified coronaviruses formed the other clique.