Interneuron FGF13 regulates seizure susceptibility via a sodium channel-independent mechanism.

Developmental and epileptic encephalopathies (DEEs), a class of devastating neurological disorders characterized by recurrent seizures and exacerbated by disruptions to excitatory/inhibitory balance in the brain, are commonly caused by mutations in ion channels. Disruption of, or variants in, were implicated as causal for a set of DEEs, but the underlying mechanisms were clouded because is expressed in both excitatory and inhibitory neurons, undergoes extensive alternative splicing producing multiple isoforms with distinct functions, and the overall roles of FGF13 in neurons are incompletely cataloged. To overcome these challenges, we generated a set of novel cell-type-specific conditional knockout mice.

Supporting General Practitioners and people with hypertension to maximise medication use to control blood pressure: the contribution of Collective Intelligence to the development of the 'Maximising Adherence, Minimising Inertia' (MIAMI) intervention.

Background: Hypertension remains one of the most important modifiable risk factors for stroke and heart disease. Anti-hypertensive medications are effective, but are often not used to maximum benefit. Sub-optimal dosing by prescribers and challenges with medication-taking for patients remain barriers to effective blood pressure control.

Interneuron FGF13 regulates seizure susceptibility via a sodium channel-independent mechanism.

Developmental and Epileptic Encephalopathies (DEEs), a class of devastating neurological disorders characterized by recurrent seizures and exacerbated by disruptions to excitatory/inhibitory balance in the brain, are commonly caused by mutations in ion channels. Disruption of, or variants in, were implicated as causal for a set of DEEs, but the underlying mechanisms were clouded because is expressed in both excitatory and inhibitory neurons, undergoes extensive alternative splicing producing multiple isoforms with distinct functions, and the overall roles of FGF13 in neurons are incompletely cataloged. To overcome these challenges, we generated a set of novel cell type-specific conditional knockout mice.

Deletion of smn-1, the Caenorhabditis elegans ortholog of the spinal muscular atrophy gene, results in locomotor dysfunction and reduced lifespan.

Spinal muscular atrophy is the most common genetic cause of infant mortality and is characterized by degeneration of lower motor neurons leading to muscle wasting. The causative gene has been identified as survival motor neuron (SMN). The invertebrate model organism Caenorhabditis elegans contains smn-1, the ortholog of human SMN.

A role for subtraction scintigraphy in the evaluation of lower gastrointestinal bleeding in the athlete.

While lower gastrointestinal haemorrhage (LGIH) in the athlete tends to be self-limiting in the majority of athletes, recurrent symptoms occur in some athletes. It is important to identify the smaller percentage of athletes in whom risks and recurrence are greater because both their general health and athletic performance might benefit from more rigorous clinical evaluation. Technetium-99m red blood cell ((99m)Tc RBC) scintigraphy is a technique for detection and localisation of LGIH and offers a number of significant advantages over other imaging modalities in the evaluation of LGIH.

Improved detection and localization of lower gastrointestinal hemorrhage using subtraction scintigraphy: clinical evaluation.

Unlabelled: Does subtraction scintigraphy improve the diagnostic utility of scintigraphic evaluation in acute lower gastrointestinal hemorrhage?

Methods: This research was a retrospective clinical study using a repeat-measures design of randomized control and experimental groups. A single patient dataset provided both the control group (conventional scintigraphy) and the experimental group (conventional and subtraction techniques). Forty-nine raw (99m)Tc-red blood cell studies were randomized and interpreted by 4 independent physicians as conventional scintigraphy data only (round 1).

Caenorhabditis elegans in the study of SMN-interacting proteins: a role for SMI-1, an orthologue of human Gemin2 and the identification of novel components of the SMN complex.

Spinal muscular atrophy is a common neuromuscular disorder caused by mutations in the survival motor neuron (SMN) gene. In mammals, SMN is tightly associated with Gemin2. To gain further insight into the functions of SMN and Gemin2, we have cloned and sequenced smi-1 (Survival of Motor neuron-Interacting protein 1), a C.

Gene expression profiling studies on Caenorhabditis elegans dystrophin mutants dys-1(cx-35) and dys-1(cx18).

The Caenorhabditis elegans genome contains a single dystrophin/utrophin orthologue, dys-1. Point mutations in this gene, dys-1(cx35) and dys-1(cx18), result in truncated proteins. Such mutants offer potentially valuable worm models of human Duchenne muscular dystrophy.

Improved detection and localization of lower gastrointestinal tract hemorrhage by subtraction scintigraphy: phantom analysis.

Unlabelled: Acute lower gastrointestinal tract hemorrhage (LGIH) has significant morbidity and mortality outcomes. Although several causes of LGIH can be life threatening, most can be effectively treated; therefore, early detection and accurate localization of bleeding sites are critical for successful patient management.

Methods: This study was a phantom experimental study with a repeated-measures design.

Steroidogenic alterations and adrenal androgen excess in PCOS.

Background: This cross-sectional study was undertaken to improve our understanding of the steroidogenic alterations leading to adrenal hyperandrogenism in polycystic ovarian syndrome (PCOS).

Methods: Two-hundred and thirty-four women with clinical and biochemical features suggestive of PCOS underwent metabolic and hormonal evaluation. We used the androstenedione/DHEAS ratio as a surrogate for the level of ovarian 3betaHSD activity.

Alpha7 mutants mimicking atypical motifs (YxxCC of loop-C, and E to H at -1' in TM2) in the C. elegans LEV-8 subunit affect nicotinic acetylcholine receptor function.

The ACR-8-like group of C. elegans nicotinic acetylcholine receptor (nAChR) subunits contain unusual motifs in the ACh binding site and in the -1' position of transmembrane region two (TM2). Using site-directed mutagenesis (SDM) we have introduced these motifs into chicken alpha7 as it has not been possible to express C.

Ovarian steroids modulate neuroendocrine dysfunction in polycystic ovary syndrome.

Objective: Neuroendocrine dysfunction in polycystic ovary syndrome (PCOS) was addressed by studying the steroid hormone changes in women with PCOS with either high or normal LH levels leading to inferences regarding the primacy of elevated LH in the pathophysiology of PCOS.

Methods: A cross-sectional study was designed in an academic clinical facility involving 234 women with PCOS. Patients were divided into two groups based on an LH/FSH ratio < or >1 and hormonal and metabolic studies were performed in both groups.

Irregular cycles and steroid hormones in polycystic ovary syndrome.

Background: This cross-sectional study was undertaken to evaluate the factors that relate to menstrual status (oligo-amenorrhoea versus eumenorrhoea) in polycystic ovary syndrome (PCOS).

Methods: A total of 234 women with clinical and biochemical features suggestive of PCOS underwent metabolic and hormonal evaluation. A forward stepwise logistic regression model was created based on the results to determine variables related to ovulatory status.

The Caenorhabditis elegans lev-8 gene encodes a novel type of nicotinic acetylcholine receptor alpha subunit.

We have cloned Caenorhabditis elegans lev-8 and demonstrated that it encodes a novel nicotinic acetylcholine receptor (nAChR) subunit (previously designated ACR-13), which has functional roles in body wall and uterine muscles as part of a levamisole-sensitive receptor. LEV-8 is an alpha subunit and is the first to be described from the ACR-8-like group, a new class of nAChR with atypical acetylcholine-binding site (loop C) and channel-lining motifs. A single base pair change in the first intron of lev-8 in lev-8(x15) mutants leads to alternative splicing and the introduction of a premature stop codon.

PCOS: an ovarian disorder that leads to dysregulation in the hypothalamic-pituitary-adrenal axis?

This review focuses on the role of the ovaries in the pathogenesis of the polycystic ovarian syndrome. In particular, the failure of follicular development, hypothalamo-pituitary dysregulation, alterations in adrenal steroid output and derangement of intermediary metabolism are discussed in the context of the ovaries. It is concluded that the central and adrenal alterations associated with PCOS are unlikely to be primary but rather are secondary to the events within the ovary.

Gene silencing of selected calcium-signalling molecules in a Drosophila cell line using double-stranded RNA interference.

Using the Drosophila melanogaster S2 cell line, stably expressing a cloned muscarinic acetylcholine receptor (AChR), DM1, we have applied gene silencing by double-stranded RNA interference (RNAi) to knock down gene products involved in DM1-mediated calcium signalling. We have shown that RNAi knock down of either the inositol 1,4,5-trisphosphate receptor (Ins(1,4,5)P(3)R), or the SERCA calcium pump in the S2-DM1 cells blocks the increase in intracellular calcium concentration ([Ca(2+)](i)) resulting from activation of the DM1 receptor by 100 microM carbamylcholine (CCh). When RNAi designed to knock down the ryanodine receptor (RyR) was tested, there was no change in the calcium increase detected in response to CCh, consistent with a failure to detect RyRs in S2-DM1 cells using RT-PCR.

A Drosophila melanogaster cell line (S2) facilitates post-genome functional analysis of receptors and ion channels.

The complete sequencing of the genome of the fruit fly Drosophila melanogaster offers the prospect of detailed functional analysis of the extensive gene families in this genetic model organism. Comprehensive functional analysis of family members is facilitated by access to a robust, stable and inducible expression system in a fly cell line. Here we show how the Schneider S2 cell line, derived from the Drosophila embryo, provides such an expression system, with the bonus that radioligand binding studies, second messenger assays, ion imaging, patch-clamp electrophysiology and gene silencing can readily be applied.

Functional genomics of ionotropic acetylcholine receptors in Caenorhabditis elegans and Drosophila melanogaster.

Genetics, genomics and electrophysiology are transforming our understanding of the nicotinic acetylcholine receptors (nAChRs). Caenorhabditis elegans contains the largest known family of nAChR subunit genes (27 members), while Drosophila melanogaster contains an exclusively neuronal nAChR gene family (10 members). In C.

Urinary tract infections.

Urinary tract infections are some of the most commonly treated bacterial infections in adults. Factors contributing to development of UTIs include personal habits, sexual habits, altered immune status, presence of diabetes, lack of estrogen and use of spermacides. Untreated or persistant UTIs may cause other more serious complications such as kidney damage or prostate infections.

Comparison of male reproductive parameters in three rat strains: Dark Agouti, Sprague-Dawley and Wistar.

The choice of experimental animal can have a large impact on experimental results, an example is the anecdotal evidence suggesting that Dark Agouti (DA) rats have a lower reproductive capacity than other rat strains. In this paper we report on an investigation into male reproductive characteristics in three rat strains--Wistar, Sprague-Dawley (outbred strains) and DA (an inbred strain). Reproductive organ weights, blood testosterone levels and sperm counts were measured in mature age-matched male rats.

Flik, a chick follistatin-related gene, functions in gastrular dorsalisation/neural induction and in subsequent maintenance of midline Sonic hedgehog signalling.

We have targetted the chick gene Flik with antisense oligodeoxynucleotide treatment at gastrular stages, when it is expressed in organiser-derived structures of the midline (K. Patel et al., 1996, Dev.

Differences in adrenal morphology in male Dark Agouti, Sprague-Dawley and Wistar rats.

There is little published information describing the differences in adrenal structure between strains of a single species despite quite well known functional differences. In this paper we report morphological differences in the adrenal glands between three strains of laboratory rat; Dark Agouti (DA), Sprague-Dawley (SD) and Wistar (W). Significant differences in adrenal weights (as a percentage of body weight) were not detected between any of the groups.

University performance, gender and the rural health workforce: an analysis of nursing students.

The relationship between student gender and performance was examined in first year students enrolled in the Bachelor of Nursing course at Charles Sturt University from 1991 to 1995. A greater proportion of female students achieved passing grades in subjects studied when compared to male students, irrespective of the subject discipline area. Furthermore, a significantly greater proportion of female than male students passed nursing subjects; however, no statistically significant differences in performance were detected in the proportion of male or female students in either science or humanities subjects.

Glial cell line-derived neurotrophic factor stimulates ureteric bud outgrowth and enhances survival of ureteric bud cells in vitro.

Development of epithelial organs requires co-ordinated interactions between epithelial and mesenchymal tissues. Studies using null mutant mice have indicated that the ret receptor and its ligand, glial cell line-derived neurotrophic factor (GDNF), are crucial for initiation of development of the metanephric kidney. However, the role of this signalling system in other branching organs has not been analysed.