Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131.

Unlabelled: Escherichia colisequence type 131 (ST131) has emerged globally as the most predominant extraintestinal pathogenic lineage within this clinically important species, and its association with fluoroquinolone and extended-spectrum cephalosporin resistance impacts significantly on treatment. The evolutionary histories of this lineage, and of important antimicrobial resistance elements within it, remain unclearly defined. This study of the largest worldwide collection (n= 215) of sequenced ST131E.

Statistical approaches and software for clustering islet cell functional heterogeneity.

Worldwide efforts are underway to replace or repair lost or dysfunctional pancreatic β-cells to cure diabetes. However, it is unclear what the final product of these efforts should be, as β-cells are thought to be heterogeneous. To enable the analysis of β-cell heterogeneity in an unbiased and quantitative way, we developed model-free and model-based statistical clustering approaches, and created new software called TraceCluster.

Multidisciplinary investigation links backward-speech trait and working memory through genetic mutation.

Case studies of unusual traits can provide unique snapshots of the effects of modified systems. In this study, we report on an individual from a Serbian family with the ability to rapidly, accurately and voluntarily speak backwards. We consider psychological, neural and genetic correlates of this trait to identify specific relevant neural mechanisms and new molecular pathways for working memory and speech-related tasks.

Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases Through a Mendelian Randomization Study.

Background: Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain.

Objectives: Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF).

Methods: This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy.

Unbiased high-throughput characterization of mussel transcriptomic responses to sublethal concentrations of the biotoxin okadaic acid.

Background. Harmful Algal Blooms (HABs) responsible for Diarrhetic Shellfish Poisoning (DSP) represent a major threat for human consumers of shellfish. The biotoxin Okadaic Acid (OA), a well-known phosphatase inhibitor and tumor promoter, is the primary cause of acute DSP intoxications.

Genetics of endometriosis.

Endometriosis is a heritable complex disorder that is influenced by multiple genetic and environmental factors. Identification of these genetic factors will aid a better understanding of the underlying biology of the disease. In this article, we describe different methods of studying genetic variation of endometriosis, summarize results from genetic studies performed to date and provide recommendations for future studies to uncover additional factors contributing to the heritable component of endometriosis.

Genetics and genomics of psychiatric disease.

Large-scale genomic investigations have just begun to illuminate the molecular genetic contributions to major psychiatric illnesses, ranging from small-effect-size common variants to larger-effect-size rare mutations. The findings provide causal anchors from which to understand their neurobiological basis. Although these studies represent enormous success, they highlight major challenges reflected in the heterogeneity and polygenicity of all of these conditions and the difficulty of connecting multiple levels of molecular, cellular, and circuit functions to complex human behavior.

Fine mapping of bone structure and strength QTLs in heterogeneous stock rat.

We previously demonstrated that skeletal structure and strength phenotypes vary considerably in heterogeneous stock (HS) rats. These phenotypes were found to be strongly heritable, suggesting that the HS rat model represents a unique genetic resource for dissecting the complex genetic etiology underlying bone fragility. The purpose of this study was to identify and localize genes associated with bone structure and strength phenotypes using 1524 adult male and female HS rats between 17 to 20 weeks of age.

Identification of an NPHP1 deletion causing adult form of nephronophthisis.

Aims: Nephronophthisis (NPHP) is an autosomal recessive cystic disease of the kidney with main characteristic features of polyuria/polydipsia, mild or absent proteinuria, interstitial fibrosis, and tubular cysts. NPHP is responsible for 5-10 % of inheritable end-stage renal disease (ESRD) cases. We investigated the clinical features and genetic cause of NPHP in a Persian family with three siblings affected by tubulointerstitial nephropathy reaching ESRD in adulthood.

Late Emergence of Parkinsonian Phenotype and Abnormal Dopamine Transporter Scan in Chorea-Acanthocytosis.

Chorea-acanthocytosis (ChAc) is a neurodegenerative condition predominantly manifesting with chorea and often acanthocytes on peripheral blood film. Abnormal appearances with I-FP-CIT single-photon emission computed tomography (SPECT) have not previously been reported in ChAc. We describe 2 cases with typical presentations of ChAc and late development of parkinsonism with asymmetric reduction in presynaptic striatal uptake on I-FP-CIT SPECT.

mutation screening in human glioblastomas.

Aims: Somatic mutations in and are described in glioblastomas (GBMs). Mutant IDH1 and IDH2 reduce α-KG to D-2HG which accumulates, and is proposed to promote tumorigenesis. HOT catalyzes the conversion of γ-hydroxybutyrate to succinic semialdehyde in a reaction that produces D-2HG.

FastMG: a simple, fast, and accurate maximum likelihood procedure to estimate amino acid replacement rate matrices from large data sets.

Background: Amino acid replacement rate matrices are a crucial component of many protein analysis systems such as sequence similarity search, sequence alignment, and phylogenetic inference. Ideally, the rate matrix reflects the mutational behavior of the actual data under study; however, estimating amino acid replacement rate matrices requires large protein alignments and is computationally expensive and complex. As a compromise, sub-optimal pre-calculated generic matrices are typically used for protein-based phylogeny.

Genome sequencing of an extended series of NDM-producing Klebsiella pneumoniae isolates from neonatal infections in a Nepali hospital characterizes the extent of community- versus hospital-associated transmission in an endemic setting.

NDM-producing Klebsiella pneumoniae strains represent major clinical and infection control challenges, particularly in resource-limited settings with high rates of antimicrobial resistance. Determining whether transmission occurs at a gene, plasmid, or bacterial strain level and within hospital and/or the community has implications for monitoring and controlling spread. Whole-genome sequencing (WGS) is the highest-resolution typing method available for transmission epidemiology.

Genetic variants underlying risk of endometriosis: insights from meta-analysis of eight genome-wide association and replication datasets.

Background: Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis.

Prognostic and therapeutic impact of argininosuccinate synthetase 1 control in bladder cancer as monitored longitudinally by PET imaging.

Targeted therapies have yet to have significant impact on the survival of patients with bladder cancer. In this study, we focused on the urea cycle enzyme argininosuccinate synthetase 1 (ASS1) as a therapeutic target in bladder cancer, based on our discovery of the prognostic and functional import of ASS1 in this setting. ASS1 expression status in bladder tumors from 183 Caucasian and 295 Asian patients was analyzed, along with its hypothesized prognostic impact and association with clinicopathologic features, including tumor size and invasion.

Dissecting quantitative traits in mice.

Progress in complex trait mapping in mice has been accelerated by the development of new populations suited to high-resolution mapping and by statistical methodologies that control for population structure. When combined with newly acquired catalogs of sequence variation in inbred strains, the genetic architecture of these new populations makes it possible to dissect complex traits down to the level of single variants. These analyses have shown not only that complex traits are caused by multiple contributing loci but also that each locus is likely due to the combined effects of multiple causal DNA variants.

Structure of a pestivirus envelope glycoprotein E2 clarifies its role in cell entry.

Enveloped viruses have developed various adroit mechanisms to invade their host cells. This process requires one or more viral envelope glycoprotein to achieve cell attachment and membrane fusion. Members of the Flaviviridae such as flaviviruses possess only one envelope glycoprotein, E, whereas pestiviruses and hepacivirus encode two glycoproteins, E1 and E2.

Patterns of co-morbidity with anxiety disorders in Chinese women with recurrent major depression.

Background: Studies conducted in Europe and the USA have shown that co-morbidity between major depressive disorder (MDD) and anxiety disorders is associated with various MDD-related features, including clinical symptoms, degree of familial aggregation and socio-economic status. However, few studies have investigated whether these patterns of association vary across different co-morbid anxiety disorders. Here, using a large cohort of Chinese women with recurrent MDD, we examine the prevalence and associated clinical features of co-morbid anxiety disorders.

A first stage genome-wide screen for regions shared identical-by-descent in Hutterite families with multiple sclerosis.

The complexity of multiple sclerosis (MS) genetics has made the search for novel genes using traditional sharing methods problematic. In order to minimize the genetic heterogeneity present in the MS population we have screened the Canadian MS population for individuals belonging to the Hutterite Brethren. Seven Hutterites with clinically definite MS were ascertained and are related to a common founder by eight generations.

Comparison of admixture and association mapping in admixed families.

The family-based admixture mapping test (AMT) identifies disease-related genes using family data from admixed individuals with the disease of interest (cases). The cases' genotypes at a set of markers are used to infer their DNA ancestry as it varies in blocks along the chromosomes. The test compares the cases' inferred ancestries to those expected from their family histories.