A Role for Basigin in Toxoplasma gondii Infection.

The role of specific host cell surface receptors during Toxoplasma gondii invasion of host cells is poorly defined. Here, we interrogated the role of the well-known malarial invasion receptor, basigin, in T. gondii infection of astrocytes.

Structural basis of lipopolysaccharide maturation by the O-antigen ligase.

The outer membrane of Gram-negative bacteria has an external leaflet that is largely composed of lipopolysaccharide, which provides a selective permeation barrier, particularly against antimicrobials. The final and crucial step in the biosynthesis of lipopolysaccharide is the addition of a species-dependent O-antigen to the lipid A core oligosaccharide, which is catalysed by the O-antigen ligase WaaL. Here we present structures of WaaL from Cupriavidus metallidurans, both in the apo state and in complex with its lipid carrier undecaprenyl pyrophosphate, determined by single-particle cryo-electron microscopy.

Structure-function studies of Rgg binding to pheromones and target promoters reveal a model of transcription factor interplay.

Regulator gene of glucosyltransferase (Rgg) family proteins, such as Rgg2 and Rgg3, have emerged as primary quorum-sensing regulated transcription factors in species, controlling virulence, antimicrobial resistance, and biofilm formation. Rgg2 and Rgg3 function is regulated by their interaction with oligopeptide quorum-sensing signals called short hydrophobic peptides (SHPs). The molecular basis of Rgg-SHP and Rgg-target DNA promoter specificity was unknown.

Structural and Functional Characterization of Phosphatidylinositol-Phosphate Biosynthesis in Mycobacteria.

In mycobacteria, phosphatidylinositol (PI) acts as a common lipid anchor for key components of the cell wall, including the glycolipids phosphatidylinositol mannoside, lipomannan, and lipoarabinomannan. Glycolipids in Mycobacterium tuberculosis, the causative agent of tuberculosis, are important virulence factors that modulate the host immune response. The identity-defining step in PI biosynthesis in prokaryotes, unique to mycobacteria and few other bacterial species, is the reaction between cytidine diphosphate-diacylglycerol and inositol-phosphate to yield phosphatidylinositol-phosphate, the immediate precursor to PI.

17p13.1 Microduplication Syndrome in a Child, Familial Short Stature, and Growth Hormone Deficiency: A Case Report and Review of the Literature.

To date, 6 cases of 17p13.1 microduplications have been described in the literature. Intellectual disability is the core feature, together with minor facial dysmorphisms and obesity.

Informed decision making and psychosocial outcomes in pregnant and nonpregnant women offered population fragile X carrier screening.

PurposePopulation-based carrier screening for fragile X syndrome (FXS) is still not universally endorsed by professional organizations due to concerns around genetic counseling for complex information and potential for psychosocial harms.MethodsWe determined uptake levels, decision making, and psychosocial impact in a prospective study of pregnant and nonpregnant Australian women offered FXS carrier screening in clinical settings. Women received pretest genetic counseling, and completed questionnaires when deciding and one month later.

Structural basis for catalysis at the membrane-water interface.

The membrane-water interface forms a uniquely heterogeneous and geometrically constrained environment for enzymatic catalysis. Integral membrane enzymes sample three environments - the uniformly hydrophobic interior of the membrane, the aqueous extramembrane region, and the fuzzy, amphipathic interfacial region formed by the tightly packed headgroups of the components of the lipid bilayer. Depending on the nature of the substrates and the location of the site of chemical modification, catalysis may occur in each of these environments.

Structures of aminoarabinose transferase ArnT suggest a molecular basis for lipid A glycosylation.

Polymyxins are antibiotics used in the last line of defense to combat multidrug-resistant infections by Gram-negative bacteria. Polymyxin resistance arises through charge modification of the bacterial outer membrane with the attachment of the cationic sugar 4-amino-4-deoxy-l-arabinose to lipid A, a reaction catalyzed by the integral membrane lipid-to-lipid glycosyltransferase 4-amino-4-deoxy-L-arabinose transferase (ArnT). Here, we report crystal structures of ArnT from Cupriavidus metallidurans, alone and in complex with the lipid carrier undecaprenyl phosphate, at 2.

Phosphoinositide control of membrane protein function: a frontier led by studies on ion channels.

Anionic phospholipids are critical constituents of the inner leaflet of the plasma membrane, ensuring appropriate membrane topology of transmembrane proteins. Additionally, in eukaryotes, the negatively charged phosphoinositides serve as key signals not only through their hydrolysis products but also through direct control of transmembrane protein function. Direct phosphoinositide control of the activity of ion channels and transporters has been the most convincing case of the critical importance of phospholipid-protein interactions in the functional control of membrane proteins.

High school Tay-Sachs disease carrier screening: 5 to 11-year follow-up.

The Melbourne high school Tay-Sachs disease (TSD) carrier screening program began in 1997. The aim of this study was to assess the outcomes of this screening program among those who had testing more than 5 years ago, to evaluate the long-term impact of screening. A questionnaire was used for data collection and consisted of validated scales and purposively designed questions.

Distant cytosolic residues mediate a two-way molecular switch that controls the modulation of inwardly rectifying potassium (Kir) channels by cholesterol and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)).

Background: Cholesterol modulates inwardly rectifying potassium (Kir) channels.

Results: A two-way molecular cytosolic switch controls channel modulation by cholesterol and PI(4,5)P(2).

Conclusion: Cholesterol and PI(4,5)P(2) induce a common gating pathway of Kir2.

The prevalence and risk factors for coeliac disease among children and adolescents with type 1 diabetes mellitus.

Aims: Our aim was to determine in children with T1DM the prevalence of positive antibodies against tissue transglutaminase (anti-tTG IgA) as indices of coeliac disease (CD), as well as its clinical presentation, its determinants and its association with thyroid (anti-TG, anti-TPO) and pancreatic b-cell autoimmunity (anti-GAD).

Methods: The study included 105 children and adolescents with T1DM, aged (mean±SD) 12.44±4.

Evaluation of a multi-disease carrier screening programme in Ashkenazi Jewish high schools.

A screening programme for Tay Sachs disease (TSD) carrier status was introduced in high schools in Victoria, Australia in 1997, and was expanded to screen for six other genetic conditions common in the Ashkenazi Jewish population in 2008. The aim of this study was to evaluate the current programme and compare it with an evaluation of the programme when screening was offered for TSD alone. All students from Jewish high schools in Melbourne who offered the programme in 2009 were invited to participate in the study.

Channelopathies linked to plasma membrane phosphoinositides.

The plasma membrane phosphoinositide phosphatidylinositol 4,5-bisphosphate (PIP2) controls the activity of most ion channels tested thus far through direct electrostatic interactions. Mutations in channel proteins that change their apparent affinity to PIP2 can lead to channelopathies. Given the fundamental role that membrane phosphoinositides play in regulating channel activity, it is surprising that only a small number of channelopathies have been linked to phosphoinositides.

Treatment with thyroxine reduces thyroid volume in euthyroid children and adolescents with chronic autoimmune thyroiditis.

Background/aims: Treatment with thyroxine in children with chronic autoimmune thyroiditis (AT) is controversial. The aim of this study is to investigate, by using thyroid ultrasonography, whether thyroxine influences thyroid volume in non-goitrous euthyroid children with AT.

Methods: We studied 50 euthyroid non-goitrous children and adolescents with AT for 2 years by thyroid function tests and ultrasonography; 25 were randomized to receive thyroxine and 25 did not receive treatment.

Population-based carrier screening for cystic fibrosis in Victoria: the first three years experience.

Background: Cystic fibrosis (CF) is the most common inherited, life-shortening condition affecting Australian children. The carrier frequency is one per 25 and most babies with CF are born to parents with no family history. Carrier testing is possible before a couple has an affected infant.

Screening for associated autoimmunity in children and adolescents with type 1 diabetes mellitus (T1DM).

Background/aims: Type 1 diabetes (T1DM) is associated with autoimmune thyroid, celiac, autoimmune gastric and Addison's disease. Our aim was to investigate the prevalence of associated autoantibodies in relation to the demographic and beta-cell autoantibody status (anti-GAD).

Methods: Antibodies against thyroid peroxidase (anti-TPO), thyroglobulin (anti-Tg), tissue transglutaminase (anti-tTG IgA), parietal cells (APCA) and adrenal tissue (AAA) were measured in 144 children with T1DM with a mean +/- SD age of 12.

Prevalence of allergic symptoms among children with diabetes mellitus type 1 of different socioeconomic status.

The aim of the study was to assess the possible associations between allergies and type 1 diabetes mellitus (DM1), stratified by social class. We studied 127 children with DM1 with a median age of 10.8 yr and 150 controls of comparable age and sex distribution.

Psychological stress as a factor potentially contributing to the pathogenesis of Type 1 diabetes mellitus.

Unlabelled: Diabetes mellitus Type 1 (T1D) is an autoimmune disorder attributed to both genetic and environmental factors. The aim of this study was to identify certain stressful conditions potentially associated with the pathogenesis and/or expression of T1D. The study group included 107 children with diabetes (CD) and 153 controls of comparable age and gender distribution at diagnosis of T1D (10.

Growth hormone deficiency in a patient with autoimmune polyendocrinopathy type 2.

Autoimmune polyglandular syndrome (APs) type 2 is characterized by the presence of Addison's disease, in association with autoimmune thyroid disease and/or type 1 diabetes mellitus and is rare in children. A 12.5 yr old prepubertal boy presented with symptoms related to Addison's disease and a large goiter.

Phosphatidylinositol-4,5-bisphosphate regulates NMDA receptor activity through alpha-actinin.

Phosphatidylinositol-4,5-bisphosphate (PIP2) has been shown to regulate many ion channels, transporters, and other signaling proteins, but it is not known whether it also regulates neurotransmitter-gated channels. The NMDA receptors (NMDARs) are gated by glutamate and serve as a critical control point in synaptic function. Here we demonstrate that PIP2 supports NMDAR activity.

Complex phenotypes in the haemoglobinopathies: recommendations on screening and DNA testing.

This document considers a number of scenarios involving complex haemoglobinopathies and provides 28 recommendations at both the clinical and laboratory levels on how these should be managed.

Factor V Leiden mutation: a contributory factor for cerebral palsy?

Fifty-seven children with cerebral palsy (CP) and imaging evidence of vascular thrombosis (study group) and 167 children with CP and other imaging finds (control group)were selected. Sixty-one per cent of the study group were male and 53 (93%) had spastic hemiplegia compared with the control group, of whom 55% were male and 54 (32%) had a diagnosis of spastic hemiplegia. Mean age was 5 years 11 months (SD 5y 1mo) for the study group and 7 years 7 months (SD 4y 7mo) for the control group.