Knockout-Induced Pluripotent Stem Cells for Disease and Therapy Modeling of IL-10-Associated Primary Immunodeficiencies.

Samples from patients with rare diseases, such as primary immunodeficiencies, are often limited, which hampers careful analysis of the pathomechanisms involved in immune cell dysregulation. To overcome this issue, induced pluripotent stem cells (iPSCs) represent an almost inexhaustible cell source and thus provide an excellent opportunity to generate disease models for rare diseases and to validate new therapeutic approaches. To obtain a better understanding of primary immunodeficiencies associated with the interleukin (IL)-10 signaling pathway, for example, very-early-onset inflammatory bowel disease (VEO-IBD), we generated genetic knockouts (KOs) of IL-10RA (IL-10 receptor α-chain) and IL-10RB (IL-10 receptor β-chain) as well as the downstream targets of the IL-10-receptor (IL-10R) signal transducers and activators of transcription (STAT)1 and STAT3 via an sgRNA (single-guide RNA)-CRISPR-Cas9-expressing lentiviral system.

[Pitfalls in the diagnostics of food allergies in children and adolescents].

For the diagnostics of food allergies several points need to be considered. Firstly, it is important to recognize the various clinical pictures that can be caused by a food allergy. The assignment to a disease decides which further examinations are necessary and reasonable.

Aiming at ecological validity-Midfrontal theta oscillations in a toy gun shooting task.

Laboratory electroencephalography (EEG) studies have already provided important insights into the neuronal mechanisms of performance monitoring. However, to our knowledge no study so far has examined neuronal correlates of performance monitoring using an ecologically valid task outside a typical laboratory setting. Therefore, we examined midfrontal theta and the feedback-related negativity (FRN) using mobile EEG in a physical shooting task within an ecologically valid environment with highly dynamical visual feedback.

The Polygenic and Monogenic Basis of Blood Traits and Diseases.

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics.

Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro.

Correction to: Microbiome definition re-visited: old concepts and new challenges.

An amendment to this paper has been published and can be accessed via the original article.

Occurrence and risk assessment of pharmaceutically active compounds in water supply systems in Brazil.

The presence of pharmaceutically active compounds (PhACs) in water supply systems has been generating great concern about their effects on the environment and human health. Twenty-eight PhACs were monitored during one year in four Brazilian water sources, aiming to understand the factors that influence their occurrence and removal in conventional drinking water treatment plants (DWTPs) and to assess the environmental and human health risks. Trace levels of PhACs were detected in surface and drinking water in all assessed water sources.

Risk Factors and Characteristics of Biphasic Anaphylaxis.

Background: Anaphylaxis is an immediate hypersensitivity reaction. However, a biphasic course with the second onset of symptoms can occur hours after the initial phase. Little is known about the causes of biphasic anaphylaxis making the identification of patients at risk difficult.

Comprehensive chemotaxonomic and genomic profiling of a biosynthetically talented Australian fungus, Aspergillus burnettii sp. nov.

Aspergillus burnettii is a new species belonging to the A. alliaceus clade in Aspergillus subgenus Circumdati section Flavi isolated from peanut-growing properties in southern Queensland, Australia. A.

Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke.

Background And Purpose: Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans.

Methods: The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts.

Long-term, open-label extension study of the efficacy and safety of epicutaneous immunotherapy for peanut allergy in children: PEOPLE 3-year results.

Background: The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250 μg).

Objective: We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study.

Methods: Subjects who completed PEPITES were offered enrollment in PEOPLE.

Microbiome definition re-visited: old concepts and new challenges.

The field of microbiome research has evolved rapidly over the past few decades and has become a topic of great scientific and public interest. As a result of this rapid growth in interest covering different fields, we are lacking a clear commonly agreed definition of the term "microbiome." Moreover, a consensus on best practices in microbiome research is missing.

Diazepam, metformin, omeprazole and simvastatin: a full discussion of individual and mixture acute toxicity.

High consumption of drugs, combined with their presence in the environment, raises concerns about its consequences. Even though researches are often engaged in analyzing substances separately, that is not the environmental reality. Therefore, the aim of this study was to investigate the acute toxicity of the pharmaceuticals simvastatin, metformin, omeprazole and diazepam, and all possible mixtures between them, to the organism Aliivibrio fischeri, verifying possible synergistic or antagonistic effects and assessing byproducts formation.

Novel keratinolytic enzymes, discovered from a talented and efficient bacterial keratin degrader.

Huge quantities of keratinaceous waste are a substantial and almost totally unexploited protein resource which could be upgraded for use as high value-added products by efficient keratinolytic enzymes. In this study, we found that Bacillus sp. 8A6 can efficiently degrade chicken feather after 24 h growth.

Ecological risk assessment of glyphosate in surface water when it is used to control floating aquatic macrophytes.

The present work evaluated the ecological risk of glyphosate by its commercial formulation (Roundup Original®) used to control floating aquatic macrophytes. Exposure analysis and ecological effects were performed from microcosm studies. The risk characterization was performed based on the calculation of the risk quotient.

[High-cost patients in Germany: General description of utilization and costs].

Background: Studies from different countries have shown that a small number of insured persons (high-cost patients) are responsible for a large portion of health care spending. At the same time, it is assumed that some of these costs could be saved by a better management of this group of people. The aim of this article is to analyze the performance and cost profiles of high-cost patients, to put them in an international comparison, and to derive a better management approach.

Conserved unique peptide patterns (CUPP) online platform: peptide-based functional annotation of carbohydrate active enzymes.

The CUPP platform includes a web server for functional annotation and sub-grouping of carbohydrate active enzymes (CAZymes) based on a novel peptide-based similarity assessment algorithm, i.e. protein grouping according to Conserved Unique Peptide Patterns (CUPP).

Interferon gamma-induced protein 10 (IP-10) and cardiovascular disease in African Americans.

Biomarkers of chronic inflammation (such as C-reactive protein) have long been associated with cardiovascular disease and mortality; however, biomarkers involved in antiviral cytokine induction and adaptive immune system activation remain largely unexamined. We hypothesized the cytokine interferon gamma inducible protein 10 (IP-10) would be associated with clinical and subclinical cardiovascular disease and all-cause mortality in African Americans. We assessed these associations in the Jackson Heart Study (JHS) cohort and the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Fungal secretome profile categorization of CAZymes by function and family corresponds to fungal phylogeny and taxonomy: Example Aspergillus and Penicillium.

Fungi secrete an array of carbohydrate-active enzymes (CAZymes), reflecting their specialized habitat-related substrate utilization. Despite its importance for fitness, enzyme secretome composition is not used in fungal classification, since an overarching relationship between CAZyme profiles and fungal phylogeny/taxonomy has not been established. For 465 Ascomycota and Basidiomycota genomes, we predicted CAZyme-secretomes, using a new peptide-based annotation method, Conserved-Unique-Peptide-Patterns, enabling functional prediction directly from sequence.

Genetic Risk for Hepatic Fat among an Ethnically Diverse Cohort of Youth: The Exploring Perinatal Outcomes among Children Study.

Objective: To assess the importance of genetic and nongenetic risk factors contributing to hepatic fat accumulation in a multiethnic population of youth.

Study Design: We investigated the relationship between genetic factors and hepatic fat fraction (HFF) in 347 children aged 12.5-19.

Non-linear Raman scattering intensities in graphene.

We show that the Raman scattering signals of the two dominant Raman bands G and 2D of graphene sensitively depend on the laser intensity in opposite ways. High electronic temperatures reached for pulsed laser excitation lead to an asymmetric Fermi-Dirac distribution at the different optically resonant states contributing to Raman scattering. This results in a partial Pauli blocking of destructively interfering quantum pathways for G band scattering, which is observed as a super-linear increase of the G band intensity with laser power.

A large-scale resource for tissue-specific CRISPR mutagenesis in .

Genetic screens are powerful tools for the functional annotation of genomes. In the context of multicellular organisms, interrogation of gene function is greatly facilitated by methods that allow spatial and temporal control of gene abrogation. Here, we describe a large-scale transgenic short guide (sg) RNA library for efficient CRISPR-based disruption of specific target genes in a constitutive or conditional manner.

Association of West African ancestry and blood pressure control among African Americans taking antihypertensive medication in the Jackson Heart Study.

African Americans have a wide range of continental genetic ancestry. It is unclear whether racial differences in blood pressure (BP) control are related to ancestral background. The authors analyzed data from the Jackson Heart Study, a cohort exclusively comprised of self-identified African Americans, to assess the association between estimated West African ancestry (WAA) and BP control (systolic and diastolic BP < 140/90 mm Hg).