Tumor grade-associated genomic mutations in Chinese patients with non-small cell lung cancer.

Background: Lung cancer is the most prevalent cancer worldwide and accounts for approximately 20% of cancer-related death in China every year. High-grade lung cancer poses a significant threat to patients, and developing a novel treatment for these patients requires an understanding of its underlying mechanism.

Methods: Chinese patients with lung cancer were enrolled.

Gene Mutations Associated With Clinical Characteristics in the Tumors of Patients With Breast Cancer.

Background: Clinical characteristics including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) are important biomarkers in the treatment of breast cancer, but how genomic mutations affect their status is rarely studied. This study aimed at finding genomic mutations associated with these clinical characteristics.

Methods: There were 160 patients with breast cancer enrolled in this study.

Clonal Evolution Dynamics in Primary and Metastatic Lesions of Pancreatic Neuroendocrine Neoplasms.

Data on inter-tumoral heterogeneity and clonal evolution of pancreatic neuroendocrine neoplasms (panNENs) with liver metastasis are limited. The aim of this study was to explore different patterns of clonal evolution of pancreatic neuroendocrine neoplasms with liver metastasis and the possible distinctive signaling pathways involved between G2 neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Tumor tissues of five patients (10 samples) with pancreatic neuroendocrine neoplasms with synchronous liver metastasis were analyzed using next-generation sequencing.

Clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.

Background: The goal of this study is to disclose the clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.

Methods: A total of 86 Chinese patients were enrolled in this study. A panel of 579 pan-cancer genes was sequenced for the qualified samples from these patients.

Genomic Mutations of Primary and Metastatic Lung Adenocarcinoma in Chinese Patients.

Lung cancer is still the leading cause of cancer-related death worldwide. Of lung cancer, lung adenocarcinoma (LUAD) is the most common subtype. Most patients with LUAD would develop into metastasis, which limits the available treatment.

Calcineurin A gamma and NFATc3/SRPX2 axis contribute to human embryonic stem cell differentiation.

Our understanding of signaling pathways regulating the cell fate of human embryonic stem cells (hESCs) is limited. Calcineurin-NFAT signaling is associated with a wide range of biological processes and diseases. However, its role in controlling hESC fate remains unclear.

Study of the co-expression gene modules of non-small cell lung cancer metastases.

Background: Metastasis regularly is a marker of the disease development of cancers. Some metastatic sites significantly showed more serious clinical outcomes in non-small cell lung cancer (NSCLC). Whether they are caused by tissue-specific (TS) or non-tissue-specific (NTS) mechanisms is still unclear.

Serial ultra-deep sequencing of circulating tumor DNA reveals the clonal evolution in non-small cell lung cancer patients treated with anti-PD1 immunotherapy.

Background: Immune-therapy with anti-PD1 inhibitors, such as pembrolizumab, is revolutionizing the treatment of non-small cell lung cancers (NSCLC). However, identifying patients for the potential therapeutic response and predicting therapy resistance and early relapse remains a challenge.

Methods: Between 2016 and 2018, 60 patients were treated with pembrolizumab, among who 12 NSCLC patients had both baseline (before treatment) and serial (on treatment) periodical circulating tumor DNA (ctDNA) samples.

Disruption of OCT4 Ubiquitination Increases OCT4 Protein Stability and ASH2L-B-Mediated H3K4 Methylation Promoting Pluripotency Acquisition.

The protein level of OCT4, a core pluripotency transcription factor, is vital for embryonic stem cell (ESC) maintenance, differentiation, and somatic cell reprogramming. However, how OCT4 protein levels are controlled during reprogramming remains largely unknown. Here, we identify ubiquitin conjugation sites of OCT4 and report that disruption of WWP2-catalyzed OCT4 ubiquitination or ablation of Wwp2 significantly promotes the efficiency of pluripotency induction from mouse embryonic fibroblasts.

Transcription coactivator Cited1 acts as an inducer of trophoblast-like state from mouse embryonic stem cells through the activation of BMP signaling.

Trophoblast lineages, precursors of the placenta, are essential for post-implantation embryo survival. However, the regulatory network of trophoblast development remains incompletely understood. Here, we report that Cited1, a transcription coactivator, is a robust inducer for trophoblast-like state from mouse embryonic stem cells (ESCs).

Progress toward elimination of perinatal HIV transmission in Kenya: Analysis of early infant diagnosis data.

Interrupting vertical transmission of HIV from mothers to infants provides opportunity to transform the HIV/AIDS epidemic by eliminating new infections among children. We estimate mother-to-child transmission rates of infants born to known HIV-positive mothers offered prevention of mother-to-child transmission interventions and provide an indication of Kenya's progress toward elimination of perinatal transmission. We obtained from the Kenya National Early Infant Diagnosis (EID) database, all 131,451 DNA polymerase chain reaction test results of HIV-exposed infants aged 0-18 months who had dried blood spot samples taken between January 2008 and October 2013.

Single-cell analysis reveals lineage segregation in early post-implantation mouse embryos.

The mammalian post-implantation embryo has been extensively investigated at the tissue level. However, to unravel the molecular basis for the cell-fate plasticity and determination, it is essential to study the characteristics of individual cells. In particular, the individual definitive endoderm (DE) cells have not been characterized Here, we report gene expression patterns in single cells freshly isolated from mouse embryos on days 5.

PHB Associates with the HIRA Complex to Control an Epigenetic-Metabolic Circuit in Human ESCs.

The chromatin landscape and cellular metabolism both contribute to cell fate determination, but their interplay remains poorly understood. Using genome-wide siRNA screening, we have identified prohibitin (PHB) as an essential factor in self-renewal of human embryonic stem cells (hESCs). Mechanistically, PHB forms protein complexes with HIRA, a histone H3.

Assessing Household Economic Vulnerability in HIV-Affected Communities in Five Regions of Côte d'Ivoire.

The objective of this study was to identify and describe levels of household economic vulnerability in HIV-affected communities in Côte d'Ivoire, defined as those with a high prevalence of HIV and large numbers of orphans and vulnerable children. We conducted a cross-sectional survey of 3,749 households in five health regions of Côte d'Ivoire. Using principal component analysis, we attempted to identify sets of correlated vulnerabilities and derive a small number of composite scores to create an index for targeting interventions to vulnerable populations.

Factors associated with HIV viral load suppression on antiretroviral therapy in Vietnam.

Background: Limited data are available on HIV viral suppression rates among men and women on antiretroviral therapy (ART) and factors associated with HIV RNA viral load (VL) suppression in Vietnam.

Methods: We conducted a cross-sectional survey of 1255 adult patients on ART for at least 1 year across four provinces in Vietnam. Data collection included a standardised questionnaire, routine laboratory testing, and an HIV VL assay.

Factors associated with HIV RNA viral loads in ART-naïve patients: implications for treatment as prevention in concentrated epidemics.

Background: Limited data are available on factors associated with HIV-RNA viral load (VL) among antiretroviral treatment (ART)-naïve key populations in concentrated epidemics.

Methods: We conducted a cross-sectional survey of 1211 adult ART-naïve patients at 19 HIV clinics in Ho Chi Minh City (HCMC), Vietnam. Data collection included a standardised questionnaire, routine laboratory testing, hepatitis serology and HIV VL.

Interventions for pain with intrauterine device insertion.

Background: Fear of pain during insertion of intrauterine contraception (IUC) is a barrier to use of this method. IUC includes copper-containing intrauterine devices and levonorgestrel-releasing intrauterine systems. Interventions for pain control during IUC insertion include non-steroidal anti-inflammatory drugs (NSAIDs), local cervical anesthetics, and cervical ripening agents such as misoprostol.

Genepleio software for effective estimation of gene pleiotropy from protein sequences.

Though pleiotropy, which refers to the phenomenon of a gene affecting multiple traits, has long played a central role in genetics, development, and evolution, estimation of the number of pleiotropy components remains a hard mission to accomplish. In this paper, we report a newly developed software package, Genepleio, to estimate the effective gene pleiotropy from phylogenetic analysis of protein sequences. Since this estimate can be interpreted as the minimum pleiotropy of a gene, it is used to play a role of reference for many empirical pleiotropy measures.

Age distribution patterns of human gene families: divergent for Gene Ontology categories and concordant between different subcellular localizations.

The age distribution of gene duplication events within the human genome exhibits two waves of duplications along with an ancient component. However, because of functional constraint differences, genes in different functional categories might show dissimilar retention patterns after duplication. It is known that genes in some functional categories are highly duplicated in the early stage of vertebrate evolution.

An update of DIVERGE software for functional divergence analysis of protein family.

DIVERGE is a software system for phylogeny-based analyses of protein family evolution and functional divergence. It provides a suite of statistical tools for selection and prioritization of the amino acid sites that are responsible for the functional divergence of a gene family. The synergistic efforts of DIVERGE and other methods have convincingly demonstrated that the pattern of rate change at a particular amino acid site may contain insightful information about the underlying functional divergence following gene duplication.

Genome factor and gene pleiotropy hypotheses in protein evolution.

The debate of genomic correlations between sequence conservation, protein connectivity, gene essentiality and gene expression, has generated a number of new hypotheses that are challenging the classical framework of molecular evolution. For instance, the translational selection hypothesis claims that the determination of the rate of protein evolution is the protein stability to avoid the misfolding toxicity. In this short article, we propose that gene pleiotropy, the capacity for affecting multiple phenotypes, may play a vital role in molecular evolution.

A preliminary analysis of gene pleiotropy estimated from protein sequences.

Biologists have long recognized the importance of gene pleiotropy, that is, single genes affect multiple traits, which is one of the most commonly observed attributes of genes. Yet the extent of gene pleiotropy has been seriously under-explored. Theoretically, Fisher's model assumed a universal pleiotropy, that is, a mutation can potentially affect all phenotypic traits.

Uncovering genetic regulatory network divergence between duplicate genes using yeast eQTL landscape.

Genetical genomics, a novel approach combining microarray technology and quantitative genetic analysis, aims to identify the expression quantitative trait loci (eQTLs), which may regulate the genome-wide expression pattern. In this article, we have studied yeast genomic eQTL data to investigate how the genetic eQTL regulation of ancestral gene has diverged since gene duplication. Our findings are as follows: (i) Duplicate genes have higher heritability for gene expression than single-copy genes, but little difference in their epistasis and directional effect.

Gene expression profiling in porcine mammary gland during lactation and identification of breed- and developmental-stage-specific genes.

A total of 28941 ESTs were sequenced from five 5'-directed non-normalized cDNA libraries, which were assembled into 2212 contigs and 5642 singlets using CAP3. These sequences were annotated and clustered into 6857 unique genes, 2072 of which having no functional annotations were considered as novel genes. These genes were further classified into Gene Ontology categories.