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Acute colitis causes alterations in the intestinal microbiota, but the microbiota is thought to recover after such events. Extreme microbiota alterations are characteristic of human chronic inflammatory bowel diseases, although alterations reported in different studies are divergent and sometimes even contradictory. To better understand the impact of periodic disturbances on the intestinal microbiota and its compositional difference between acute and relapsing colitis, we investigated the beginnings of recurrent inflammation using the dextran sodium sulfate (DSS) mouse model of chemically induced colitis. Using bacterial 16S rRNA gene-targeted pyrosequencing as well as quantitative fluorescence in situ hybridization, we profiled the intestinal and stool microbiota of mice over the course of three rounds of DSS-induced colitis and recovery. We found that characteristic inflammation-associated microbiota could be detected in recovery-phase mice. Successive inflammation episodes further drove the microbiota into an increasingly altered composition post-inflammation, and signatures of colitis history were detectable in the microbiota more sensitively than by pathology analysis. Bacterial indicators of murine colitis history were identified in intestinal and stool samples, with a high degree of consistency between both sample types. Stool may therefore be a promising non-invasive source of bacterial biomarkers that are highly sensitive to inflammation state and history.

Decades of cardiovascular research have shown that variable and flexible levels of protein phosphorylation are necessary to maintain cardiac function. A delicate balance between phosphorylated and dephosphorylated states of proteins is guaranteed by a complex interplay of protein kinases (PK) and phosphatases. Serine/threonine phosphatases, in particular members of the protein phosphatase (PP) family govern dephosphorylation of the majority of these cardiac proteins. Recent findings have however shown that PPs do not only dephosphorylate previously phosphorylated proteins as a passive control mechanism but are capable to actively control PK activity via different direct and indirect signaling pathways. These control mechanisms can take place on (epi-)genetic, (post-)transcriptional and (post-)translational levels. In addition PPs themselves are targets of a plethora of proteinaceous interaction partner regulating their endogenous activity, thus adding another level of complexity and feedback control towards this system. Finally, novel approaches are underway to achieve spatiotemporal pharmacologic control of protein phosphatases which in turn can be used to fine-tune misleaded protein kinase activity in heart disease. Taken together, this review comprehensively summarizes the major aspects of PP-mediated PK regulation and discusses the subsequent consequences of deregulated PP activity for cardiovascular diseases in depth.

Schizotypy refers to a set of temporally stable traits that are observed in the general population and that resemble the signs and symptoms of schizophrenia. Here, we review evidence from studies on genetics, cognition, perception, motor and oculomotor control, brain structure, brain function and psychopharmacology in schizotypy. We specifically focused on identifying areas of overlap between schizotypy and schizophrenia. Evidence was corroborated that significant overlap exists between the two, covering the behavioural, brain structural and functional as well molecular levels. In particular, several studies showed that individuals with high levels of schizotypal traits exhibit alterations in neurocognitive task performance and underlying brain function similar to the deficits seen in patients with schizophrenia. Studies of brain structure have shown both volume reductions and increases in schizotypy, pointing to schizophrenia-like deficits as well as possible protective or compensatory mechanisms. Experimental pharmacological studies have shown that high levels of schizotypy are associated with (i) enhanced dopaminergic response in striatum following administration of amphetamine and (ii) improvement of cognitive performance following administration of antipsychotic compounds. Together, this body of work suggests that schizotypy shows overlap with schizophrenia across multiple behavioural and neurobiological domains, suggesting that the study of schizotypal traits may be useful in improving our understanding of the aetiology of schizophrenia.

Next Generation Sequencing studies generate a large quantity of genetic data in a relatively cost and time efficient manner and provide an unprecedented opportunity to identify candidate causative variants that lead to disease phenotypes. A challenge to these studies is the generation of sequencing artifacts by current technologies. To identify and characterize the properties that distinguish false positive variants from true variants, we sequenced a child and both parents (trio) using DNA isolated from three sources (blood, buccal cells, and saliva). The trio strategy allowed us to identify variants in the proband that could not have been inherited from the parents (Mendelian errors) and would most likely indicate sequencing artifacts. Quality control measurements were examined and three measurements were found to identify the greatest number of Mendelian errors. These included read depth, genotype quality score, and alternate allele ratio. Filtering the variants on these measurements removed ~95% of the Mendelian errors while retaining 80% of the called variants. These filters were applied independently. After filtering, the concordance between identical samples isolated from different sources was 99.99% as compared to 87% before filtering. This high concordance suggests that different sources of DNA can be used in trio studies without affecting the ability to identify causative polymorphisms. To facilitate analysis of next generation sequencing data, we developed the Cincinnati Analytical Suite for Sequencing Informatics (CASSI) to store sequencing files, metadata (e.g. relatedness information), file versioning, data filtering, variant annotation, and identify candidate causative polymorphisms that follow either de novo, rare recessive homozygous or compound heterozygous inheritance models. We conclude the data cleaning process improves the signal to noise ratio in terms of variants and facilitates the identification of candidate disease causative polymorphisms.

Common variation at the loci harboring the fat mass and obesity gene (FTO), MC4R and TMEM18 are consistently reported as being associated with obesity and body mass index especially in adult population. In order to confirm this effect in pediatric population five European ancestry cohorts from pediatric eMERGE-II network (CCHMC-BCH) were evaluated.Method:Data on 5049 samples of European ancestry were obtained from the Electronic Medical Records (EMRs) of two large academic centers in five different genotyped cohorts. For all available samples, gender, age, height and weight were collected and Body Mass Index (BMI) was calculated. To account for age and sex differences in BMI, BMI z-scores were generated using 2000 Centers of Disease Control and Prevention (CDC) growth charts. A Genome-wide association study (GWAS) was performed with BMI z-score. After removing missing data and outliers based on principal components (PC) analyses, 2860 samples were used for the GWAS study. The association between each SNP and BMI was tested using linear regression adjusting for age, gender, and PC by cohort. The effects of SNPs were modeled assuming additive, recessive and dominant effects of the minor allele. Meta-analysis was conducted using a weighted z-score approach. Results:The mean age of subjects was 9.8 years (range 2-19). The proportion of male subjects was 56%. In these cohorts, 14% of samples had a BMI≥95% and 28%≥85%. Meta analyses produced a signal at 16q12 genomic region with the best result of p=1.43x10E-07 (p (rec)=7.34E-08) for the single nucleotide polymorphism (SNP) rs8050136 at the first intron of FTO gene (z=5.26) and with no heterogeneity between cohorts (p=0.77). Imputation in this region using dense 1000-Genome and Hapmap CEU samples revealed 71 SNPs with p

Freshwater wetlands are a major source of the greenhouse gas methane but at the same time can function as carbon sink. Their response to global warming and environmental pollution is one of the largest unknowns in the upcoming decades to centuries. In this review, we highlight the role of sulfate-reducing microorganisms (SRM) in the intertwined element cycles of wetlands. Although regarded primarily as methanogenic environments, biogeochemical studies have revealed a previously hidden sulfur cycle in wetlands that can sustain rapid renewal of the small standing pools of sulfate. Thus, dissimilatory sulfate reduction, which frequently occurs at rates comparable to marine surface sediments, can contribute up to 36–50% to anaerobic carbon mineralization in these ecosystems. Since sulfate reduction is thermodynamically favored relative to fermentative processes and methanogenesis, it effectively decreases gross methane production thereby mitigating the flux of methane to the atmosphere. However, very little is known about wetland SRM. Molecular analyses using dsrAB [encoding subunit A and B of the dissimilatory (bi)sulfite reductase] as marker genes demonstrated that members of novel phylogenetic lineages, which are unrelated to recognized SRM, dominate dsrAB richness and, if tested, are also abundant among the dsrAB-containing wetland microbiota. These discoveries point towards the existence of so far unknown SRM that are an important part of the autochthonous wetland microbiota. In addition to these numerically dominant microorganisms, a recent stable isotope probing study of SRM in a German peatland indicated that rare biosphere members might be highly active in situ and have a considerable stake in wetland sulfate reduction. The hidden sulfur cycle in wetlands and the fact that wetland SRM are not well represented by described SRM species explains their so far neglected role as important actors in carbon cycling and climate change.