Unaltered Hypothalamic Metabolic Gene Expression in Kiss1r Knockout Mice Despite Obesity and Reduced Energy Expenditure.

Kisspeptin controls reproduction by stimulating gonadotrophin-releasing hormone neurones via its receptor Kiss1r. Kiss1r is also expressed other brain areas and in peripheral tissues, suggesting additional nonreproductive roles. We recently determined that Kiss1r knockout (KO) mice develop an obese and diabetic phenotype.

A comparison of carcass decomposition and associated insect succession onto burnt and unburnt pig carcasses.

The rate of decomposition and insect succession onto decomposing pig carcasses were investigated following burning of carcasses. Ten pig carcasses (40-45 kg) were exposed to insect activity during autumn (March-April) in Western Australia. Five replicates were burnt to a degree described by the Crow-Glassman Scale (CGS) level #2, while five carcasses were left unburnt as controls.

Levels of inflammation and oxidative stress, and a role for taurine in dystropathology of the Golden Retriever Muscular Dystrophy dog model for Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is a fatal skeletal muscle wasting disease presenting with excessive myofibre necrosis and increased inflammation and oxidative stress. In the mdx mouse model of DMD, homeostasis of the amino acid taurine is altered, and taurine administration drastically decreases muscle necrosis, dystropathology, inflammation and protein thiol oxidation. Since the severe pathology of the Golden Retriever Muscular Dystrophy (GRMD) dog model more closely resembles the human DMD condition, we aimed to assess the generation of oxidants by inflammatory cells and taurine metabolism in this species.

The impact of non-severe burn injury on cardiac function and long-term cardiovascular pathology.

Severe burn injury significantly affects cardiovascular function for up to 3 years. However, whether this leads to long-term pathology is unknown. The impact of non-severe burn injury, which accounts for over 80% of admissions in developed countries, has not been investigated.

Targeting Single Molecules in Asthma Benefits Few.

Asthma is a lung disorder triggered by various airborne factors in susceptible individuals. Although generally controlled, asthma can be severe and difficult to treat. Presently, increasing numbers of pharmaceuticals capable of blocking or mimicking specific endogenous molecules are undergoing clinical trials in asthmatic individuals whose symptoms are poorly controlled despite adherence to guideline therapies.

Increased taurine in pre-weaned juvenile mdx mice greatly reduces the acute onset of myofibre necrosis and dystropathology and prevents inflammation.

Background: The mdx mouse model for the fatal muscle wasting disease Duchenne Muscular Dystrophy (DMD) shows a very mild pathology once growth has ceased, with low levels of myofibre necrosis in adults. However, from about 3 weeks of post-natal age, muscles of juvenile mdx mice undergo an acute bout of severe necrosis and inflammation: this subsequently decreases and stabilises to lower adult levels by about 6 weeks of age. Prior to the onset of this severe dystropathology, we have shown that mdx mice are deficient in the amino acid taurine (potentially due to weaning), and we propose that this exacerbates myofibre necrosis and inflammation in juvenile mdx mice.

Structural, super-resolution microscopy analysis of paraspeckle nuclear body organization.

Paraspeckles are nuclear bodies built on the long noncoding RNA Neat1, which regulates a variety of physiological processes including cancer progression and corpus luteum formation. To obtain further insight into the molecular basis of the function of paraspeckles, we performed fine structural analyses of these nuclear bodies using structural illumination microscopy. Notably, paraspeckle proteins are found within different layers along the radially arranged bundles of Neat1 transcripts, forming a characteristic core-shell spheroidal structure.

Behavioral Variation in Gorillas: Evidence of Potential Cultural Traits.

The question of whether any species except humans exhibits culture has generated much debate, partially due to the difficulty of providing conclusive evidence from observational studies in the wild. A starting point for demonstrating the existence of culture that has been used for many species including chimpanzees and orangutans is to show that there is geographic variation in the occurrence of particular behavioral traits inferred to be a result of social learning and not ecological or genetic influences. Gorillas live in a wide variety of habitats across Africa and they exhibit flexibility in diet, behavior, and social structure.

A structure-function analysis of the left ventricle.

This study presents a structure-function analysis of the mammalian left ventricle and examines the performance of the cardiac capillary network, mitochondria, and myofibrils at rest and during simulated heavy exercise. Left ventricular external mechanical work rate was calculated from cardiac output and systemic mean arterial blood pressure in resting sheep (Ovis aries; n = 4) and goats (Capra hircus; n = 4) under mild sedation, followed by perfusion-fixation of the left ventricle and quantification of the cardiac capillary-tissue geometry and cardiomyocyte ultrastructure. The investigation was then extended to heavy exercise by increasing cardiac work according to published hemodynamics of sheep and goats performing sustained treadmill exercise.

Household resources and seasonal patterns of child growth in rural Timor-Leste.

Objectives: This study aimed to determine through detailed contextual investigation the effects of seasonal resource shortages, and household and individual level differences, on child growth in rural Timor-Leste. We compared trends in growth across two rural Timorese villages with different ecologies.

Methods: Heads of 104 households in Natarbora, Timor-Leste, were interviewed and resource levels assessed during the food shortage season.

Mother-infant cultural group selection.

Richerson et al. argue that "cultural group selection plays an essential role in explaining human cooperation." We believe that cooperation came first, making culture and thus cultural group selection possible.

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: study protocol for a randomized controlled trial.

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs.

Waking up dormant tumor suppressor genes with zinc fingers, TALEs and the CRISPR/dCas9 system.

The aberrant epigenetic silencing of tumor suppressor genes (TSGs) plays a major role during carcinogenesis and regaining these dormant functions by engineering of sequence-specific epigenome editing tools offers a unique opportunity for targeted therapies. However, effectively normalizing the expression and regaining tumor suppressive functions of silenced TSGs by artificial transcription factors (ATFs) still remains a major challenge. Herein we describe novel combinatorial strategies for the potent reactivation of two class II TSGs, MASPIN and REPRIMO, in cell lines with varying epigenetic states, using the CRISPR/dCas9 associated system linked to a panel of effector domains (VP64, p300, VPR and SAM complex), as well as with protein-based ATFs, Zinc Fingers and TALEs.

Protocol of the PLeural Effusion And Symptom Evaluation (PLEASE) study on the pathophysiology of breathlessness in patients with symptomatic pleural effusions.

Introduction: Pleural effusion is a common clinical problem that can complicate many medical conditions. Breathlessness is the most common symptom of pleural effusion of any cause and the most common reason for pleural drainage. However, improvement in breathlessness following drainage of an effusion is variable; some patients experience either no benefit or a worsening of their breathlessness.

Socioeconomic disadvantage and oral-health-related hospital admissions: a 10-year analysis.

Objective: The aim of this Western Australian population study was to assess the relationship of socioeconomic disadvantage and: 1) trends in hospitalisations for oral-health-related conditions over 10 years; 2) insurance status, costs and length of stay in hospital; and 3) specific conditions (principal diagnosis) patients were admitted for.

Methods: Hospitalisation data (of oral-health-related conditions) were obtained for every episode of discharge from all hospitals in Western Australia for the financial years 1999-2000 to 2008-2009. Area based measures (using the Index of Relative Socioeconomic Disadvantage) was used to determine relationships between socioeconomic status and other variables.

Obesity Disrupts the Rhythmic Profiles of Maternal and Fetal Progesterone in Rat Pregnancy.

Maternal obesity increases the risk of abnormal fetal growth, but the underlying mechanisms remain unclear. Because steroid hormones regulate fetal growth, and both pregnancy and obesity markedly alter circadian biology, we hypothesized that maternal obesity disrupts the normal rhythmic profiles of steroid hormones in rat pregnancy. Obesity was established by cafeteria (CAF) feeding for 8 wk prior to mating and throughout pregnancy.

A three-dimensional co-culture system to investigate macrophage-dependent tumor cell invasion.

Macrophages infiltrate cancers and promote progression to invasion and metastasis. To directly examine tumor-associated macrophages (TAMs) and tumor cells interacting and co-migrating in a three-dimensional (3D) environment, we have developed a co-culture model that uses a PyVmT mouse mammary tumor-derived cell line and mouse bone marrow-derived macrophages (BMM). The Py8119 cell line was cloned from a spontaneous mammary tumor in a Tg(MMTV:LTR-PyVmT) C57Bl/6 mouse and these cells form 3-dimensional (3D) spheroids under conditions of low adhesion.

Curved bones: An adaptation to habitual loading.

Why are long bones curved? It has long been considered a paradox that many long bones supporting mammalian bodies are curved, since this curvature results in the bone undergoing greater bending, with higher strains and so greater fracture risk under load. This study develops a theoretical model wherein the curvature is a response to bending strains imposed by the requirements of locomotion. In particular the radioulna of obligate quadrupeds is a lever operated by the triceps muscle, and the bending strains induced by the triceps muscle counter the bending resulting from longitudinal loads acting on the curved bone.

Is There a Relation between ABO Blood Groups and Clinical Outcome in Patients with Pemphigoid? A Case-Control Study.

Background. Relationship between blood groups and dermatologic diseases remains controversial and was not yet fully elucidated nor explained clearly. The aim of this study was to examine if any relation exists between different types of pemphigoid diseases and ABO blood group.

Accuracy of a cut-off value based on the third molar index: Validation in an Australian population.

According to Recommendation N°196 of the Australian Law Reform Commission (ALRC), the age at which a child reaches adulthood for the purposes of criminal law should be 18 years in all Australian jurisdictions. With specific reference to age at majority, the only tooth with development spanning adolescence (and thus the legally relevant 18 years of age) is the third molar, which limits the number of methods that can be applied from those available in the published literature. The aim of the present study is to test the accuracy of the third molar index (I3M=0.

Pregnancy Suppresses the Daily Rhythmicity of Core Body Temperature and Adipose Metabolic Gene Expression in the Mouse.

Maternal adaptations in lipid metabolism are crucial for pregnancy success due to the role of white adipose tissue as an energy store and the dynamic nature of energy needs across gestation. Because lipid metabolism is regulated by the rhythmic expression of clock genes, it was hypothesized that maternal metabolic adaptations involve changes in both adipose clock gene expression and the rhythmic expression of downstream metabolic genes. Maternal core body temperature (Tc) was investigated as a possible mechanism driving pregnancy-induced changes in clock gene expression.

Pregnancy-induced changes in the circadian expression of hepatic clock genes: implications for maternal glucose homeostasis.

Adaptations in maternal carbohydrate metabolism are particularly important in pregnancy because glucose is the principal energy substrate used by the fetus. As metabolic homeostasis is intricately linked to the circadian system via the rhythmic expression of clock genes, it is likely that metabolic adaptations during pregnancy also involve shifts in maternal circadian function. We hypothesized that maternal adaptation in pregnancy involves changes in the hepatic expression of clock genes, which drive downstream shifts in circadian expression of glucoregulatory genes.