Context-Specific Protein Network Miner – An Online System for Exploring Context-Specific Protein Interaction Networks from the Literature

Background: Protein interaction networks (PINs) specific within a particular context contain crucial information regarding many cellular biological processes. For example, PINs may include information on the type and directionality of interaction (e.g. phosphorylation), location of interaction (i.e. tissues, cells), and related diseases. Currently, very few tools are capable of deriving context-specific PINs for conducting exploratory analysis. Results: We developed a literature-based online system, Context-specific Protein Network Miner (CPNM), which derives context-specific PINs in real-time from the PubMed database based on a set of user-input keywords and enhanced PubMed query system. CPNM reports enriched information on protein interactions (with type and directionality), their network topology with summary statistics (e.g. most densely connected proteins in the network; most densely connected protein-pairs; and proteins connected by most inbound/outbound links) that can be explored via a user-friendly interface. Some of the novel features of the CPNM system include PIN generation, ontology-based PubMed query enhancement, real-time, user-queried, up-to-date PubMed document processing, and prediction of PIN directionality. Conclusions: CPNM provides a tool for biologists to explore PINs. It is freely accessible at http://www.biotextminer.com/CPNM/.Statistic

Mammalian sex determination—insights from humans and mice

Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Many of the genes required for gonad development have been identified by analysis of DSD patients. However, the use of knockout and transgenic mouse strains have contributed enormously to the study of gonad gene function and interactions within the development network. Although the genetic basis of mammalian sex determination and differentiation has advanced considerably in recent years, a majority of 46,XY gonadal dysgenesis patients still cannot be provided with an accurate diagnosis. Some of these unexplained DSD cases may be due to mutations in novel DSD genes or genomic rearrangements affecting regulatory regions that lead to atypical gene expression. Here, we review our current knowledge of mammalian sex determination drawing on insights from human DSD patients and mouse models

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems

New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous WIA in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little, while not much new information has been gathered on soil organisms. The impact on marine coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal classneonicotinoids and fipronil. , withContinued large scale – mostly prophylactic – use of these persistent organochlorine pesticides has the potential to greatly decreasecompletely eliminate populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates, and their deleterious impacts on growth, reproduction and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al. 2015)

CYP1A1, GSTM1 and GSTT1 polymorphisms, tobacco and alcohol status and risk of head and neck squamous cell carcinoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)We examined the influence of the CYP1A1 A4889G and T6235C, GSTM1 and GSTT1 polymorphisms, involved in carcinogen metabolism, on the head and neck (HN) squamous cell carcinoma (SCC) risk. DNA from 142 HNSCC patients and 142 controls was analysed by polymerase chain reaction (PCR)-restriction fragment length polymorphism or multiplex-PCR for the polymorphisms analyses. Excesses of the CYP1A1 4889AG+GG and 4889AG+GG plus GSTT1 null genotype were seen in patients with heavy tobacco habit compared with controls (41.9% versus 26.8%, P=0.03; 26.2% versus 10.3%, P=0.04, respectively). Carriers of the referred genotypes and heavy tobacco consumption were under a 2.0-fold and 2.8-fold increased risks for HNSCC than others, respectively. The CYP1A1 6235TC+CC plus GSTM1 and GSTT1 null genotypes were more common in pharyngeal SCC patients than in controls (5.3% versus 0.7%, P=0.04). Carriers of the combined genotype had 16.0-fold increased risk for the disease than others. The frequency of one null genotype of the GSTM1 or GSTT1 gene was higher in patients with pharyngeal SCC and heavy smoking status than in controls (76.3% versus 57.7%, P=0.04). Carriers of the referred genotype and heavy tobacco status had a 2.4-fold increased risk for pharyngeal SCC than others. In contrast, the CYP1A1 6235TC+CC genotype was more common in controls than in laryngeal SCC patients (35.9% versus 21.6%, P=0.01). Carriers of the genotype had a 0.2-fold decreased risk for the disease than others. Our data present preliminary evidence that inherited combined CYP1A1 A4889G and T6235C abnormalities and GSTM1 and GSTT1 pathways are important determinants of HNSCC, particularly pharyngeal SCC in heavy smoking individuals from southeastern Brazil.32612091215Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financiadora de Estudos e Projetos do Ministerio da Ciencia e Tecnologia do Brasil (FINEP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq