The Five Faces of Notch Signalling During Drosophila melanogaster Embryonic CNS Development.

During central nervous system (CNS) development, a complex series of events play out, starting with the establishment of neural progenitor cells, followed by their asymmetric division and formation of lineages and the differentiation of neurons and glia. Studies in the Drosophila melanogaster embryonic CNS have revealed that the Notch signal transduction pathway plays at least five different and distinct roles during these events. Herein, we review these many faces of Notch signalling and discuss the mechanisms that ensure context-dependent and compartment-dependent signalling.

Accumulation of genetic variants associated with immunity in the selective breeding of broilers.

Background: To satisfy an increasing demand for dietary protein, the poultry industry has employed genetic selection to increase the growth rate of broilers by over 400% in the past 50 years. Although modern broilers reach a marketable weight of ~ 2 kg in a short span of 35 days, a speed twice as fast as a broiler 50 years ago, the expedited growth has been associated with several negative detrimental consequences. Aside from heart and musculoskeletal problems, which are direct consequences of additional weight, the immune response is also thought to be altered in modern broilers.

Hyperpolarized Xe imaging of embryonic stem cell-derived alveolar-like macrophages in rat lungs: proof-of-concept study using superparamagnetic iron oxide nanoparticles.

Purpose: To measure regional changes in hyperpolarized Xe MRI signal and apparent transverse relaxation ( ) because of instillation of SPION-labeled alveolar-like macrophages (ALMs) in the lungs of rats and compare to histology.

Methods: MRI was performed in 6 healthy mechanically ventilated rats before instillation, as well as 5 min and 1 h after instillation of 4 million SPION-labeled ALMs into either the left or right lung. maps were calculated from 2D multi-echo data at each time point and changes in were measured and compared to control rats receiving 4 million unlabeled ALMs.

PopNetD3-A Network-Based Web Resource for Exploring Population Structure.

We present PopNetD3, a web tool that provides an integrated approach for the network-based visualization of population structure based on the PopNet clustering framework. Users first submit a tab-delimited file that defines diversity of SNPs across the genome which is subsequently processed by the PopNet backend to define patterns of conservation at the chromosome level. The resulting population structure is visualized through a dedicated D3-based tool, allowing users to interactively examine chromosomal regions predicted to share ancestry.

Progression of Cystic Fibrosis Lung Disease from Childhood to Adulthood: Neutrophils, Neutrophil Extracellular Trap (NET) Formation, and NET Degradation.

Genetic defects in cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene cause CF. Infants with CFTR mutations show a peribronchial neutrophil infiltration prior to the establishment of infection in their lung. The inflammatory response progressively increases in children that include both upper and lower airways.

Preliminary Definitions for Sacroiliac Joint Pathologies in the OMERACT Juvenile Idiopathic Arthritis Magnetic Resonance Imaging Score (OMERACT JAMRIS-SIJ).

Objective: To develop definitions for the assessment of magnetic resonance imaging (MRI) pathologies of the sacroiliac joints (SIJ) in juvenile idiopathic arthritis.

Methods: An Outcome Measures in Rheumatology (OMERACT) consensus-driven methodology consisting of iterative surveys and focus group meetings within an international group of rheumatologists and radiologists.

Results: Two domains, inflammation and structural, were identified.

Design and application of a novel two-amplicon approach for defining eukaryotic microbiota.

Background: Due to a lack of systematic diagnostics, our understanding of the diversity and role of eukaryotic microbiota in human health is limited. While studies have shown fungal communities to be significant modulators of human health, information on the prevalence of taxa such as protozoa and helminths has been limited to a small number of species for which targeted molecular diagnostics are available. To probe the diversity of eukaryotic microbes and their relationships with other members of the microbiota, we applied in silico and experimental approaches to design a novel two-amplicon surveillance tool, based on sequencing regions of ribosomal RNA genes and their internal transcribed spacers.

Methodologic recommendations and possible interpretations of video-EEG recordings in immature rodents used as experimental controls: A TASK1-WG2 report of the ILAE/AES Joint Translational Task Force.

The use of immature rodents to study physiologic aspects of cortical development requires high-quality recordings electroencephalography (EEG) with simultaneous video recording (vEEG) of behavior. Normative developmental vEEG data in control animals are fundamental for the study of abnormal background activity in animal models of seizures or other neurologic disorders. Electrical recordings from immature, freely behaving rodents can be particularly difficult because of the small size of immature rodents, their thin and soft skull, interference with the recording apparatus by the dam, and other technical challenges.

Lactobacillus elicits a 'Marmite effect' on the chicken cecal microbiome.

The poultry industry has traditionally relied on the use of antibiotic growth promoters (AGPs) to improve production efficiency and minimize infection. With the recent drive to eliminate the use of AGPs, novel alternatives are urgently required. Recently attention has turned to the use of synthetic communities that may be used to 'seed' the developing microbiome.

An in vivo screen for neuronal genes involved in obesity identifies Diacylglycerol kinase as a regulator of insulin secretion.

Objective: Obesity is a complex disorder involving many genetic and environmental factors that are required to maintain energy homeostasis. While studies in human populations have led to significant progress in the generation of an obesity gene map and broadened our understanding of the genetic basis of common obesity, there is still a large portion of heritability and etiology that remains unknown. Here, we have used the genetically tractable fruit fly, Drosophila melanogaster, to identify genes/pathways that function in the nervous system to regulate energy balance.

Cdh1 and Pik3ca Mutations Cooperate to Induce Immune-Related Invasive Lobular Carcinoma of the Breast.

CDH1 and PIK3CA are the two most frequently mutated genes in invasive lobular carcinoma (ILC) of the breast. Transcription profiling has identified molecular subtypes for ILC, one of which, immune-related (IR), is associated with gene expression linked to lymphocyte and macrophage infiltration. Here, we report that deletion of Cdh1, together with activation of Pik3ca in mammary epithelium of genetically modified mice, leads to formation of IR-ILC-like tumors with immune cell infiltration, as well as gene expression linked to T-regulatory (Treg) cell signaling and activation of targetable immune checkpoint pathways.

Animal models of necrotizing enterocolitis: review of the literature and state of the art.

Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal surgical emergency in preterm neonates. Over the last five decades, a variety of experimental models have been developed to study the pathophysiology of this disease and to test the effectiveness of novel therapeutic strategies. Experimental NEC is mainly modeled in neonatal rats, mice and piglets.

Ceramide-induced BOK promotes mitochondrial fission in preeclampsia.

Mitochondria are in a constant balance of fusing and dividing in response to cellular cues. Fusion creates healthy mitochondria, whereas fission results in removal of non-functional organelles. Changes in mitochondrial dynamics typify several human diseases.

Maternal depressive symptoms linked to reduced fecal Immunoglobulin A concentrations in infants.

Secretory Immunoglobulin A (sIgA) plays a critical role to infant gut mucosal immunity. Delayed IgA production is associated with greater risk of allergic disease. Murine models of stressful events during pregnancy and infancy show alterations in gut immunity and microbial composition in offspring, but little is known about the stress-microbiome-immunity pathways in humans.

Variability of Creatine Metabolism Genes in Children with Autism Spectrum Disorder.

Creatine deficiency syndrome (CDS) comprises three separate enzyme deficiencies with overlapping clinical presentations: arginine:glycine amidinotransferase ( gene, glycine amidinotransferase), guanidinoacetate methyltransferase ( gene), and creatine transporter deficiency ( gene, solute carrier family 6 member 8). CDS presents with developmental delays/regression, intellectual disability, speech and language impairment, autistic behaviour, epileptic seizures, treatment-refractory epilepsy, and extrapyramidal movement disorders; symptoms that are also evident in children with autism. The objective of the study was to test the hypothesis that genetic variability in creatine metabolism genes is associated with autism.

Diverse structures, functions and uses of FK506 binding proteins.

FK506 (Tacrolimus), isolated from Streptomyces tsukubaenis is a powerful immunosuppressant shown to inhibit T cell activation. FK506 mediated immunosuppression requires the formation of a complex between FK506, a FK506 binding protein (FKBP) and calcineurin. Numerous FKBPs have been identified in a wide range of species, from single celled organisms to humans.

Progress and inequities in maternal mortality in Afghanistan (RAMOS-II): a retrospective observational study.

Background: The risk of maternal death in Afghanistan is among the highest in the world; however, the risks within the country are poorly understood. Subnational maternal mortality estimates are needed along with a broader understanding of determinants to guide future maternal health programmes. Here we aimed to study maternal mortality risk and causes, care-seeking patterns, and costs within the country.

Novel homozygous PCK1 mutation causing cytosolic phosphoenolpyruvate carboxykinase deficiency presenting as childhood hypoglycemia, an abnormal pattern of urine metabolites and liver dysfunction.

Clinical and laboratory data were collected from three Finnish patients including a sibling pair and another unrelated child with unexplained childhood hypoglycemia. Transient elevation of alanine transaminase, lactate and tricarboxylic acid cycle intermediates, especially fumarate, were noticed in urine organic acid analysis. Exome sequencing was performed for the patients and their parents.

Social pediatrics: weaving horizontal and vertical threads through pediatric residency.

Background: Social pediatrics teaches pediatric residents how to understand disease within their patients' social, environmental and political contexts. It's an essential component of pediatric residency training; however there is very little literature that addresses how such a broad-ranging topic can be taught effectively. The aim of this study was to determine and characterize social pediatric education in our pediatric residency training in order to identify strengths and gaps.

An MRspec database query and visualization engine with applications as a clinical diagnostic and research tool.

Purpose: Proton magnetic resonance spectroscopy (MRspec), one of the very few techniques for in vivo assessment of neuro-metabolic profiles, is often complicated by lack of standard population norms and paucity of computational tools.

Methods: 7035 scans and clinical information from 4430 pediatric patients were collected from 2008 to 2014. Scans were conducted using a 1.

The NHR domains of Neuralized and related proteins: Beyond Notch signalling.

Neuralized Homology Repeats (NHRs) were first identified in Neuralized, an E3-ubiquitin ligase that plays a key role in the Notch signalling pathway. Since their original discovery, NHR domains have been shown to regulate protein-protein interactions in a broad range of developmental processes and in a wide variety of species from flies to humans. The NHR family of proteins can be categorized into three groups: (1) those that contain a RING finger, (2) those that contain a SOCS box and, (3) those that only have NHR domains.

Systemic availability of guanidinoacetate affects GABAA receptor function and seizure threshold in GAMT deficient mice.

Deficiency of guanidinoacetate methyltransferase (GAMT) causes creatine depletion and guanidinoacetate accumulation in brain with the latter deemed to be responsible for the severe seizure disorder seen in affected patients. We studied electrical brain activity and GABAA mediated mechanisms of B6J.Cg-Gamt(tm1Isb) mice.

Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality.

Background: Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging.

Prevalence of Creatine Deficiency Syndromes in Children With Nonsyndromic Autism.

Background And Objective: Creatine deficiency may play a role in the neurobiology of autism and may represent a treatable cause of autism. The goal of the study was to ascertain the prevalence of creatine deficiency syndromes (CDSs) in children with autism spectrum disorder (ASD).

Methods: In a prospective multicenter study, 443 children were investigated after a confirmed diagnosis of ASD.