Clinical exome sequencing data from patients with inborn errors of immunity: Cohort level diagnostic yield and the benefit of systematic reanalysis.

While next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use and re-use of exome sequencing is still emerging. We revisited clinical exome data from 1300 IEI patients using an updated in silico IEI gene panel. Variants were classified and curated through expert review.

Using a thermal gradient table to study plant temperature signalling and response across a temperature spectrum.

Plants must cope with ever-changing temperature conditions in their environment. In many plant species, suboptimal high and low temperatures can induce adaptive mechanisms that allow optimal performance. Thermomorphogenesis is the acclimation to high ambient temperature, whereas cold acclimation refers to the acquisition of cold tolerance following a period of low temperatures.

Detection of DNA Contamination in Prenatal Samples from Whole Exome Sequencing Data.

Background: Maternal cell contamination (MCC) in prenatal samples poses a risk for misdiagnosis, and therefore, testing for contamination is necessary during genetic analysis of prenatal specimens. MCC testing is currently performed as a method separate from the diagnostic method. With the increasing application of whole exome sequencing (WES) in prenatal diagnosis, we sought to develop a method to estimate the level of contamination from WES data, aiming to eliminate the need for a separate MCC test.

Developmental shift in testosterone influence on prefrontal emotion control.

A paradox of testosterone effects is seen in adolescents versus adults in social emotional approach-avoidance behavior. During adolescence, high testosterone levels are associated with increased anterior prefrontal (aPFC) involvement in emotion control, whereas during adulthood this neuro-endocrine relation is reversed. Rodent work shows that, during puberty, testosterone transitions from a neuro-developmental to a social-sexual activating hormone.

Arabidopsis thaliana rosette habit is controlled by combined light and energy signaling converging on transcriptional control of the TALE homeobox gene ATH1.

In the absence of light signals, Arabidopsis plants fail to develop the rosette habit typical for this species. Instead, plants display caulescent growth due to elongation of rosette internodes. This aspect of photomorphogenic development has been paid little attention and molecular events involved, downstream of photoreceptor signaling, remain to be identified.

All-in-one whole exome sequencing strategy with simultaneous copy number variant, single nucleotide variant and absence-of-heterozygosity analysis in fetuses with structural ultrasound anomalies: A 1-year experience.

Objective: We performed a 1-year evaluation of a novel strategy of simultaneously analyzing single nucleotide variants (SNVs), copy number variants (CNVs) and copy-number-neutral Absence-of-Heterozygosity from Whole Exome Sequencing (WES) data for prenatal diagnosis of fetuses with ultrasound (US) anomalies and a non-causative QF-PCR result.

Methods: After invasive diagnostics, whole exome parent-offspring trio-sequencing with exome-wide CNV analysis was performed in pregnancies with fetal US anomalies and a non-causative QF-PCR result (WES-CNV). On request, additional SNV-analysis, restricted to (the) requested gene panel(s) only (with the option of whole exome SNV-analysis afterward) was performed simultaneously (WES-CNV/SNV) or as rapid SNV-re-analysis, following a normal CNV analysis.

Trajectories of loneliness across adolescence: An empirical comparison of longitudinal clustering methods using R.

Introduction: In this study, we compare three different longitudinal clustering methods. As a case study, the comparison of the methods is conducted for the development of loneliness from middle childhood to young adulthood. The aim is to explore how two nonparametric longitudinal cluster methods compare with a model-based latent class mixture model approach.

Clinical exome sequencing-Mistakes and caveats.

Massive parallel sequencing technology has become the predominant technique for genetic diagnostics and research. Many genetic laboratories have wrestled with the challenges of setting up genetic testing workflows based on a completely new technology. The learning curve we went through as a laboratory was accompanied by growing pains while we gained new knowledge and expertise.

An integrative genomics approach identifies KDM4 as a modulator of trained immunity.

Innate immune cells are able to build memory characteristics via a process termed "trained immunity." Host factors that influence the magnitude of the individual trained immunity response remain largely unknown. Using an integrative genomics approach, our study aimed to prioritize and understand the role of specific genes in trained immunity responses.

Seasonal and Nonseasonal Longitudinal Variation of Immune Function.

Different components of the immune response show large variability between individuals, but they also vary within the same individual because of host and environmental factors. In this study, we report an extensive analysis of the immune characteristics of 56 individuals over four timepoints in 1 single year as part of the Human Functional Genomics Project. We characterized 102 cell subsets using flow cytometry; quantified production of eight cytokines and two chemokines in response to 20 metabolic, bacterial, fungal, and viral stimuli; and measured circulating markers of inflammation.

Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease.

Background: Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors.

Result: We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation.

The chemical compound 'Heatin' stimulates hypocotyl elongation and interferes with the Arabidopsis NIT1-subfamily of nitrilases.

Temperature passively affects biological processes involved in plant growth. Therefore, it is challenging to study the dedicated temperature signalling pathways that orchestrate thermomorphogenesis, a suite of elongation growth-based adaptations that enhance leaf-cooling capacity. We screened a chemical library for compounds that restored hypocotyl elongation in the pif4-2-deficient mutant background at warm temperature conditions in Arabidopsis thaliana to identify modulators of thermomorphogenesis.

Human recombinant interleukin-38 suppresses inflammation in mouse models of local and systemic disease.

Interleukin (IL)-38 belongs to the IL-1 family and is part of the IL-36 subfamily due to its binding to the IL-36 Receptor (IL-1R6). In the current study, we assessed the anti-inflammatory properties of IL-38 in murine models of arthritis and systemic inflammation. First, the anti-inflammatory properties of mouse and human IL-38 precursors were compared to forms with a truncated N-terminus.

Safety and COVID-19 Symptoms in Individuals Recently Vaccinated with BCG: a Retrospective Cohort Study.

Bacille Calmette-Guérin (BCG) induces long-term boosting of innate immunity, termed trained immunity, and decreases susceptibility to respiratory tract infections. BCG vaccination trials for reducing SARS-CoV-2 infection are underway, but concerns have been raised regarding the potential harm of strong innate immune responses. To investigate the safety of BCG vaccination, we retrospectively assessed coronavirus disease 2019 (COVID-19) and related symptoms in three cohorts of healthy volunteers who either received BCG in the last 5 years or did not.

MYC2-Activated Acetylates Cell Walls and Enhances Herbivore Resistance.

-Acetylation of polysaccharides predominantly modifies plant cell walls by changing the physicochemical properties and, consequently, the structure and function of the cell wall. Expression regulation and specific function of cell wall-acetylating enzymes remain to be fully understood. In this report, we cloned a previously identified stunted growth mutant named () in Arabidopsis ().

Sex-Specific Regulation of Inflammation and Metabolic Syndrome in Obesity.

Objective: Metabolic dysregulation and inflammation are important consequences of obesity and impact susceptibility to cardiovascular disease. Anti-inflammatory therapy in cardiovascular disease is being developed under the assumption that inflammatory pathways are identical in women and men, but it is not known if this is indeed the case. In this study, we assessed the sex-specific relation between inflammation and metabolic dysregulation in obesity.

Platelet Integrin αIIbβ3 Activation is Associated with 25-Hydroxyvitamin D Concentrations in Healthy Adults.

Background:  Cardiovascular events are associated with low circulating vitamin D concentrations, although the underlying mechanisms are poorly understood. This study investigated associations between 25-hydroxyvitamin D concentrations, platelet function, and single-nucleotide polymorphisms (SNPs) in genes influencing vitamin D biology in the 500 Functional Genomics (500FG) cohort.

Methods:  In this observational study, platelet activation and function were measured by flow cytometry by binding of fibrinogen to the activated fibrinogen receptor integrin αIIbβ3 and expression of P-selectin, markers of platelet aggregation and degranulation, respectively.

HISTONE DEACETYLASE 9 stimulates auxin-dependent thermomorphogenesis in by mediating H2A.Z depletion.

Many plant species respond to unfavorable high ambient temperatures by adjusting their vegetative body plan to facilitate cooling. This process is known as thermomorphogenesis and is induced by the phytohormone auxin. Here, we demonstrate that the chromatin-modifying enzyme HISTONE DEACETYLASE 9 (HDA9) mediates thermomorphogenesis but does not interfere with hypocotyl elongation during shade avoidance.

Metabolite Control of Translation by Conserved Peptide uORFs: The Ribosome as a Metabolite Multisensor.

Ribosomes translate the mRNA code into protein, and this process can be controlled by metabolites that bind to the translating ribosome in interaction with the nascent protein.

Parenting quality in infancy and emotional eating in adolescence: Mediation through emotion suppression and alexithymia.

This study assessed the association between parenting quality at age 15 and 28 months and emotional eating (EE) at age 12 and 16 years through serial mediation by suppression of emotions and alexithymia at 12 years. The sample included 129 children and their parents. Lower parental quality in infancy was related to more suppression of emotions, which in turn was related to more difficulty identifying emotions, and in turn to higher EE in adolescence.

A Genome-Wide Functional Genomics Approach Identifies Susceptibility Pathways to Fungal Bloodstream Infection in Humans.

Background: Candidemia, one of the most common causes of fungal bloodstream infection, leads to mortality rates up to 40% in affected patients. Understanding genetic mechanisms for differential susceptibility to candidemia may aid in designing host-directed therapies.

Methods: We performed the first genome-wide association study on candidemia, and we integrated these data with variants that affect cytokines in different cellular systems stimulated with Candida albicans.

Friends and foes: Neural correlates of prosocial decisions with peers in adolescence.

Adolescence is a critical period for social orientation to peers and for developing social skills in interactions with peers. In the current study we examined the neural correlates of prosocial decisions for friends and disliked peers, and their links with participants' friendship quality and empathy as indices of social competence. Participants' friends and disliked peers were identified using sociometric nominations.