An Open-Source Tool for Investigation of Differential RNA Expression Between Spinal Cord Cells of Male and Female Mice.

Chronic pain is a highly debilitating condition that differs by type, prevalence, and severity between men and women. To uncover the molecular underpinnings of these differences, it is critical to analyze the transcriptomes of spinal cord pain-processing networks for both sexes. Despite several recently published single-nucleus RNA-sequencing (snRNA-seq) studies on the function and composition of the mouse spinal cord, a gene expression analysis investigating the differences between males and females has yet to be performed.

A long-term dataset of topography and nearshore bathymetry at the macrotidal pocket beach of Porsmilin, France.

Long-term datasets documenting the evolution of coastal forms and processes, through the provision of recurring beach as well as shoreface morphological observations and accompanying time-series of environmental controls, remain difficult to collect and are rarely made available. However, they are increasingly needed to further our understanding of coastal change and to improve the models that will help planning what our future coast will be. This data descriptor presents the results of topographic and bathymetric surveys at Porsmilin, a macrotidal embayed beach situated in Brittany, northwest France.

Multicenter Validation Study to Implement Plasma Epidermal Growth Factor Receptor T790M Testing in Clinical Laboratories.

Purpose: Plasma detection of T790M mutations is an emerging alternative to tumor rebiopsy in acquired epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance. Validation of analytical sensitivity and clinical utility is required before routine diagnostic use in clinical laboratories.

Patients And Methods: Sixty-three patients with advanced -mutant lung cancer at 7 Canadian centers, who were being screened for the ASTRIS trial (ClinicalTrials.

The devolution of the social licence to operate in the Australian mining industry.

The aim of this paper is to present a brief historical analysis of the Australian mining industry and the development of its social licence to operate. Commencing with the discovery of coal in the 18th century, to gold and copper and base metals in the 19th century, to the world class iron ore, mineral sands and diamond mines of the 20th century to the current day, the paper will attempt to determine how and why an industry, formerly well-respected by the public, is considered to be a pariah in the eyes of many sections of society. The theory of social licence and its use in the Australian minerals industry is briefly described and a working definition of "an honest, transparent engagement resulting in a beneficial outcome to all parties before, during and after mining" is adopted throughout the paper.

Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent.

Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO < 10 mmHg) after the termination of seizures.

An Algorithm for Neuropathic Pain Management in Older People.

Neuropathic pain frequently affects older people, who generally also have several comorbidities. Elderly patients are often poly-medicated, which increases the risk of drug-drug interactions. These patients, especially those with cognitive problems, may also have restricted communication skills, making pain evaluation difficult and pain treatment challenging.

Gene delivery in mouse auditory brainstem and hindbrain using in utero electroporation.

Background: Manipulation of gene expression via recombinant viral vectors and creation of transgenic knock-out/in animals has revolutionized our understanding of genes that play critical roles during neuronal development and pathophysiology of neurological disorders. Recently, target-specific genetic manipulations are made possible to perform in combination with specific Cre-lines, albeit costly, labor-intensive and time consuming. Thus, alternative methods of gene manipulations to address important biological questions are highly desirable.

Splice-variant changes of the Ca(V)3.2 T-type calcium channel mediate voltage-dependent facilitation and associate with cardiac hypertrophy and development.

Low voltage-activated T-type calcium (Ca) channels contribute to the normal development of the heart and are also implicated in pathophysiological states such as cardiac hypertrophy. Functionally distinct T-type Ca channel isoforms can be generated by alternative splicing from each of three different T-type genes (Ca(V)3.1, Ca(V)3.

Pinostrobin from Cajanus cajan (L.) Millsp. inhibits sodium channel-activated depolarization of mouse brain synaptoneurosomes.

This investigation focuses on the in vitro neuroactive properties of pinostrobin, a substituted flavanone from Cajanus cajan (L.) Millsp. of the Fabaceae family.

Ca(V)2.1 P/Q-type calcium channel alternative splicing affects the functional impact of familial hemiplegic migraine mutations: implications for calcium channelopathies.

Alternative splicing is known to generate multiple functionally distinct calcium channel variants that exhibit unique spatial and temporal expression patterns. In humans, naturally occurring mutations in genes encoding calcium channel pore forming alpha(1)-subunits are associated with several severe hereditary disorders although it remains to be described whether there exists any relationship between the physiological effects of these mutations and calcium channel splice variation. In the present study, we systematically compare the biophysical effects of three type-1 familial hemiplegic migraine (FHM-1) mutations in two predominant splice variants of the neuronal Ca(V)2.

A Cav3.2 T-type calcium channel point mutation has splice-variant-specific effects on function and segregates with seizure expression in a polygenic rat model of absence epilepsy.

Low-voltage-activated, or T-type, calcium (Ca(2+)) channels are believed to play an essential role in the generation of absence seizures in the idiopathic generalized epilepsies (IGEs). We describe a homozygous, missense, single nucleotide (G to C) mutation in the Ca(v)3.2 T-type Ca(2+) channel gene (Cacna1h) in the genetic absence epilepsy rats from Strasbourg (GAERS) model of IGE.

Molecular mechanisms of subtype-specific inhibition of neuronal T-type calcium channels by ascorbate.

T-type Ca2+ channels (T-channels) are involved in the control of neuronal excitability and their gating can be modulated by a variety of redox agents. Ascorbate is an endogenous redox agent that can function as both an anti- and pro-oxidant. Here, we show that ascorbate selectively inhibits native Ca(v)3.

Selective inhibition of Cav3.3 T-type calcium channels by Galphaq/11-coupled muscarinic acetylcholine receptors.

T-type calcium channels play critical roles in controlling neuronal excitability, including the generation of complex spiking patterns and the modulation of synaptic plasticity, although the mechanisms and extent to which T-type Ca(2+) channels are modulated by G-protein-coupled receptors (GPCRs) remain largely unexplored. To examine specific interactions between T-type Ca(2+) channel subtypes and muscarinic acetylcholine receptors (mAChRS), the Cav3.1 (alpha(1G)), Cav3.

Safety rules and regulations on mine sites - the problem and a solution.

Introduction: Many accidents and incidents on mine sites have a causal factor in the rules and regulations that supposedly are in place to prevent the incident from occurring. The causes involve a lack of awareness or understanding, ignorance, or deliberate violations. The issue of mine rules, procedures, and regulations is a central focus of this paper, highlighted by this recent comment - "very few people have accidents for which there is no procedure in place.

Quantitation of paralytic shellfish toxins using mouse brain synaptoneurosomes.

A membrane potential assay based on synaptoneurosomes prepared from mouse brain was evaluated further for its utility in estimating saxitoxin and related bioactives. Saxitoxin concentrations quantitated in mussel extracts by the synaptoneurosomal technique correlated well with spiked concentrations in these samples (r2 = 0.995; slope=1.

Inhibition of voltage-sensitive sodium channels by the cannabinoid 1 receptor antagonist AM 251 in mammalian brain.

The cannabinoid 1 receptor antagonist AM 251 is known to block the inhibitory effects of endocannabinoids and synthetic cannabinoid agonists on transmitter release through an action at presynaptic cannabinoid 1 receptors in brain. We examined the ability of AM 251 to inhibit sodium channel-dependent functions and the binding of [3H]batrachotoxinin A 20-alpha-benzoate to sodium channels in mouse brain synaptic preparations. Depolarization of synaptoneurosomes by the sodium channel site 2-specific neurotoxin veratridine, which is abolished by tetrodotoxin, was found to be inhibited in a concentration-dependent fashion by AM 251 (IC50=8.

A rapid assay for the brevetoxin group of sodium channel activators based on fluorescence monitoring of synaptoneurosomal membrane potential.

A functional pharmacologically-based assay for the brevetoxin group of sodium channel activators was developed using synaptoneurosomes isolated from the brains of CD1 mice. The assay can detect the depolarizing effect of brevetoxin congeners PbTx-2 and PbTx-3 as enhancements of the veratridine-dependent increase in fluorescence of the voltage-sensitive fluorescent probe rhodamine 6G. The assay is relatively rapid and can detect brevetoxin activity in the nanomolar range.