Towards understanding sex differences in autism spectrum disorders.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social deficits, repetitive behaviours and lack of empathy. Its significant genetic heritability and potential comorbidities often lead to diagnostic and therapeutic challenges. This review addresses the biological basis of ASD, focusing on the sex differences in gene expression and hormonal influences.

Rapid electrophoretic deposition of biocompatible graphene coatings for high-performance recording neural electrodes.

The electrical and biological interfacial properties of invasive electrodes have a significant impact on the performance and longevity of neural recordings in the brain. In this study, we demonstrated rapid electrophoretic deposition and electrochemical reduction of graphene oxide (GO) on metal-based neural electrodes. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and other characterizations confirmed the existence of a uniform and effectively reduced graphene oxide coating.

Inwardly rectifying potassium channels mediate polymyxin-induced nephrotoxicity.

Polymyxin antibiotics are often used as a last-line defense to treat life-threatening Gram-negative pathogens. However, polymyxin-induced kidney toxicity is a dose-limiting factor of paramount importance and can lead to suboptimal treatment. To elucidate the mechanism and develop effective strategies to overcome polymyxin toxicity, we employed a whole-genome CRISPR screen in human kidney tubular HK-2 cells and identified 86 significant genes that upon knock-out rescued polymyxin-induced toxicity.

Autism-associated miR-873 regulates ARID1B, SHANK3 and NRXN2 involved in neurodevelopment.

Autism spectrum disorders (ASD) are highly heritable neurodevelopmental disorders with significant genetic heterogeneity. Noncoding microRNAs (miRNAs) are recognised as playing key roles in development of ASD albeit the function of these regulatory genes remains unclear. We previously conducted whole-exome sequencing of Australian families with ASD and identified four novel single nucleotide variations in mature miRNA sequences.

β-tripeptides act as sticky ends to self-assemble into a bioscaffold.

Peptides comprised entirely of β-amino acids, commonly referred to as β-foldamers, have been shown to self-assemble into a range of materials. Previously, β-foldamers have been functionalised via various side chain chemistries to introduce function to these materials without perturbation of the self-assembly motif. Here, we show that insertion of both rigid and flexible molecules into the backbone structure of the β-foldamer did not disturb the self-assembly, provided that the molecule is positioned between two β-tripeptides.

A novel conditional mouse model for Nkx2-5 reveals transcriptional regulation of cardiac ion channels.

Nkx2-5 is one of the master regulators of cardiac development, homeostasis and disease. This transcription factor has been previously associated with a suite of cardiac congenital malformations and impairment of electrical activity. When disease causative mutations in transcription factors are considered, NKX2-5 gene dysfunction is the most common abnormality found in patients.

Diminished hERG K+ channel activity facilitates strong human labour contractions but is dysregulated in obese women.

Human ether-a-go-go-related gene (hERG) potassium channels determine cardiac action potential and contraction duration. Human uterine contractions are underpinned by an action potential that also possesses an initial spike followed by prolonged depolarization. Here we show that hERG channel proteins (α-conducting and β-inhibitory subunits) and hERG currents exist in isolated patch-clamped human myometrial cells.

Voltage-operated Ca(2) (+) currents and Ca(2) (+) -activated Cl(-) currents in single interstitial cells of the guinea-pig prostate.

Objective: To investigate the expression of 'T-type' and 'L-type' voltage-operated Ca(2) (+) channels in single interstitial cells of the guinea-pig prostate.

Material And Methods: Whole-cell and perforated patch-clamp techniques were applied to prostatic interstitial cells (PICs) dispersed using collagenase.

Results: In contrast to prostatic myocytes, PICs under voltage clamp and filled with K(+) (130 mm) were distinguished by the absence of a voltage-operated transient outward K(+) current or spike discharge upon membrane depolarisation when under current clamp.

Comparative study on the therapeutic potential of neurally differentiated stem cells in a mouse model of multiple sclerosis.

Background: Transplantation of neural stem cells (NSCs) is a promising novel approach to the treatment of neuroinflammatory diseases such as multiple sclerosis (MS). NSCs can be derived from primary central nervous system (CNS) tissue or obtained by neural differentiation of embryonic stem (ES) cells, the latter having the advantage of readily providing an unlimited number of cells for therapeutic purposes. Using a mouse model of MS, we evaluated the therapeutic potential of NSCs derived from ES cells by two different neural differentiation protocols that utilized adherent culture conditions and compared their effect to primary NSCs derived from the subventricular zone (SVZ).

Neural differentiation of patient specific iPS cells as a novel approach to study the pathophysiology of multiple sclerosis.

The recent introduction of technologies capable of reprogramming human somatic cells into induced pluripotent stem (iPS) cells offers a unique opportunity to study many aspects of neurodegenerative diseases in vitro that could ultimately lead to novel drug development and testing. Here, we report for the first time that human dermal fibroblasts from a patient with relapsing-remitting Multiple Sclerosis (MS) were reprogrammed to pluripotency by retroviral transduction using defined factors (OCT4, SOX2, KLF4, and c-MYC). The MSiPS cell lines resembled human embryonic stem (hES) cell-like colonies in morphology and gene expression and exhibited silencing of the retroviral transgenes after four passages.

Potassium and ANO1/ TMEM16A chloride channel profiles distinguish atypical and typical smooth muscle cells from interstitial cells in the mouse renal pelvis.

Background And Purpose: Although atypical smooth muscle cells (SMCs) in the proximal renal pelvis are thought to generate the pacemaker signals that drive pyeloureteric peristalsis, their location and electrical properties remain obscure.

Experimental Approach: Standard patch clamp, intracellular microelectrode and immunohistochemistry techniques were used. To unequivocally identify SMCs, transgenic mice with enhanced yellow fluorescent protein (eYFP) expressed in cells containing α-smooth muscle actin (α-SMA) were sometimes used.

Spontaneous electrical and Ca2+ signals in the mouse renal pelvis that drive pyeloureteric peristalsis.

1. Peristalsis in the smooth muscle cell (SMC) wall of the pyeloureteric system is unique in physiology in that the primary pacemaker resides in a population of atypical SMCs situated near the border of the renal papilla. 2.

Spontaneous electrical and Ca2+ signals in typical and atypical smooth muscle cells and interstitial cell of Cajal-like cells of mouse renal pelvis.

Electrical rhythmicity in the renal pelvis provides the fundamental drive for the peristaltic contractions that propel urine from the kidney to bladder for storage until micturition. Although atypical smooth muscles (ASMCs) within the most proximal regions of the renal pelvis have long been implicated as the pacemaker cells, the presence of a sparsely distributed population of rhythmically active Kit-positive interstitial cells of Cajal-like cells (ICC-LCs) have confounded our understanding of pelviureteric peristalsis. We have recorded the electrical activity and separately visualized changes in intracellular Ca(2+) concentration in typical smooth muscle cells (TSMCs), ASMCs and ICC-LCs using intracellular microelectrodes and a fluorescent Ca(2+) indicator, fluo-4.

Pyeloureteric peristalsis: role of atypical smooth muscle cells and interstitial cells of Cajal-like cells as pacemakers.

Pyeloureteric peristalsis has long been considered to be triggered by pacemaker atypical smooth muscle cells (SMC) located in the proximal regions of the renal pelvis. However, interstitial cells with many of the morphological features and c-Kit immuno-reactivity of interstitial cells of Cajal (ICC), the established pacemaker cells in the intestine, have been demonstrated to be present in small numbers within the ureteropelvic junction (UPJ) of many mammals. Freshly isolated ICC-like cells (ICC-LC) of the mouse UPJ also display autorhyhmicity.