Sexual Dimorphism: increased sterol excretion leads to hypocholesterolaemia in female hyperbilirubinaemic Gunn rats

KEY POINTS: Female adult hyperbilirubinaemic (Gunn) rats demonstrated lower circulating cholesterol corroborating human studies that report a negative association between bilirubin and cholesterol concentrations. Furthermore, female Gunn rats had elevated sterol excretion creating a negative intestinal sterol balance that was compensated for by elevated cholesterol synthesis and increased hepatic LDL receptor expression. Therefore, elevated LDL receptor expression potentially leads to reduced circulating cholesterol levels in female Gunn rats providing an explanation for the hypocholesterolaemia observed in humans with elevated bilirubin levels. This study also reports a novel interaction of sex with the hyperbilirubinaemic phenotype on sterol metabolism because changes were only reported in females and not in male Gunn rats. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome). ABSTRACT: Background Circulating bilirubin is associated with reduced serum cholesterol concentrations in humans and in hyperbilirubinaemic Gunn rats. However, mechanisms contributing to hypocholesterolaemia remain unknown. Therefore, this study aimed to investigate cholesterol synthesis, transport, and excretion in mutant Gunn rats. Methods Adult Gunn and control rats were assessed for daily faecal sterol excretion using metabolic cages and water was supplemented with [1-13 C]-acetate to determine cholesterol synthesis. Bile was collected to measure biliary lipid secretion. Serum and liver were collected for biochemical analysis and for gene/protein expression using RT-qPCR and western blot, respectively. Additionally, serum was collected and analysed from juvenile rats. Results A significant interaction of sex, age, and phenotype on circulating lipids was found with adult female Gunn rats reporting significantly lower cholesterol and phospholipids. Female Gunn rats also demonstrated elevated cholesterol synthesis, greater biliary lipid secretion, and increased total faecal cholesterol and bile acid excretion. Furthermore, they possessed increased hepatic LDL receptor and SREBP2 expression. In contrast, there was no changes to sterol metabolism in adult male Gunn rats. Conclusions This is the first study to demonstrate elevated faecal sterol excretion in female hyperbilirubinaemic Gunn rats. Increased sterol excretion creates a negative intestinal sterol balance that is compensated for by increased cholesterol synthesis and LDL receptor expression. Therefore, reduced circulating cholesterol is potentially caused by increased hepatic uptake via the LDL receptor. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome). Abstract figure legend This article is protected by copyright. All rights reserved

High brightness semiconductor lasers as transmitters for space lidar systems

High brightness semiconductor lasers are potential transmitters for future space lidar systems. In the framework of the European Project BRITESPACE, we propose an all-semiconductor laser source for an Integrated Path Differential Absorption lidar system for column-averaged measurements of atmospheric CO2 in future satellite missions. The complete system architecture has to be adapted to the particular emission properties of these devices using a Random Modulated Continuous Wave approach. We present the initial experimental results of the InGaAsP/InP monolithic Master Oscillator Power Amplifiers, providing the ON and OFF wavelengths close to the selected absorption line around 1572 nm

The Role of Thailand in the International Trade in CITES-Listed Live Reptiles and Amphibians

BACKGROUND: International wildlife trade is one of the leading threats to biodiversity conservation. The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) is the most important initiative to monitor and regulate the international trade of wildlife but its credibility is dependent on the quality of the trade data. We report on the performance of CITES reporting by focussing on the commercial trade in non-native reptiles and amphibians into Thailand as to illustrate trends, species composition and numbers of wild-caught vs. captive-bred specimens. METHODOLOGY/PRINCIPAL FINDINGS: Based on data in the WCMC-CITES trade database, we establish that a total of 75,594 individuals of 169 species of reptiles and amphibians (including 27 globally threatened species) were imported into Thailand in 1990-2007. The majority of individuals (59,895, 79%) were listed as captive-bred and a smaller number (15,699, 21%) as wild-caught. In the 1990s small numbers of individuals of a few species were imported into Thailand, but in 2003 both volumes and species diversity increased rapidly. The proportion of captive-bred animals differed greatly between years (from 0 to >80%). Wild-caught individuals were mainly sourced from African countries, and captive-bred individuals from Asian countries (including from non-CITES Parties). There were significant discrepancies between exports and imports. Thailand reports the import of >10,000 individuals (51 species) originating from Kazakhstan, but Kazakhstan reports no exports of these species. Similar discrepancies, involving smaller numbers (>100 individuals of 9 species), can be seen in the import of reptiles into Thailand via Macao. CONCLUSION/SIGNIFICANCE: While there has been an increase in imports of amphibian and reptiles into Thailand, erratic patterns in proportions of captive-bred specimens and volumes suggests either capricious markets or errors in reporting. Large discrepancies with respect to origin point to misreporting or possible violations of the rules and intentions of CITES

Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

Event-related alpha suppression in response to facial motion

This article has been made available through the Brunel Open Access Publishing Fund.While biological motion refers to both face and body movements, little is known about the visual perception of facial motion. We therefore examined alpha wave suppression as a reduction in power is thought to reflect visual activity, in addition to attentional reorienting and memory processes. Nineteen neurologically healthy adults were tested on their ability to discriminate between successive facial motion captures. These animations exhibited both rigid and non-rigid facial motion, as well as speech expressions. The structural and surface appearance of these facial animations did not differ, thus participants decisions were based solely on differences in facial movements. Upright, orientation-inverted and luminance-inverted facial stimuli were compared. At occipital and parieto-occipital regions, upright facial motion evoked a transient increase in alpha which was then followed by a significant reduction. This finding is discussed in terms of neural efficiency, gating mechanisms and neural synchronization. Moreover, there was no difference in the amount of alpha suppression evoked by each facial stimulus at occipital regions, suggesting early visual processing remains unaffected by manipulation paradigms. However, upright facial motion evoked greater suppression at parieto-occipital sites, and did so in the shortest latency. Increased activity within this region may reflect higher attentional reorienting to natural facial motion but also involvement of areas associated with the visual control of body effectors. © 2014 Girges et al

LIDAR System based on a High Brightness Semiconductor Laser and Single Photon Counting Detection for Space -borne Atmospheric CO2 Monitoring

We theoretically investigate a dynamical regime, experimentally observed in monolithically integrated master oscillator power amplifiers emitting at 1.5 7 μm, consisting in large emission wavelength jumps of the device from the Bragg wavelength to that of the gain peak. Our analysis is based on numerical simulations by means of a travelling wave model that incorporates spatial effects such as spatial hole burning and coupled-cavity effects. Thermal effects are included by considering the optical response of the quantum well active medium within the quasi-equilibrium approximation at finite temperature, with a phenomenological description of the redshift of the gain peak and the changes in the background material refractive index by means of self- and cross-heating coefficients for both sections. We find that whereas the thermally-induced index changes are the responsible of the modal jumps between consecutive modes, the carrier-induced refractive index changes are the responsible of the jumps occurring between the Bragg wavelength and the gain peak

Nest desertion is not predicted by cuckoldry in the Eurasian penduline tit

Engagement in extra-pair copulations is an example of the abundant conflicting interests between males and females over reproduction. Potential benefits for females and the risk of cuckoldry for males are expected to have important implications on the evolution of parental care. However, whether parents adjust parental care in response to parentage remains unclear. In Eurasian penduline tits Remiz pendulinus, which are small polygamous songbirds, parental care is carried out either by the male or by the female. In addition, one third of clutches is deserted by both male and female. Desertion takes place during the egg-laying phase. Using genotypes of nine microsatellite loci of 443 offspring and 211 adults, we test whether extra-pair paternity predicts parental care. We expect males to be more likely to desert cuckolded broods, whereas we expect females, if they obtain benefits from having multiple sires, to be more likely to care for broods with multiple paternity. Our results suggest that parental care is not adjusted to parentage on an ecological timescale. Furthermore, we found that male attractiveness does not predict cuckoldry, and we found no evidence for indirect benefits for females (i.e., increased growth rates or heterozygosity of extra-pair offspring). We argue that male Eurasian penduline tits may not be able to assess the risk of cuckoldry; thus, a direct association with parental care is unlikely to evolve. However, timing of desertion (i.e., when to desert during the egg-laying phase) may be influenced by the risk of cuckoldry. Future work applying extensive gene sequencing and quantitative genetics is likely to further our understanding of how selection may influence the association between parentage and parental care

Back to Basics: Pitting Edema and the Optimization of Hypertension Treatment in Incident Peritoneal Dialysis Patients (BRAZPD)

Systemic arterial hypertension is an important risk factor for cardiovascular disease that is frequently observed in populations with declining renal function. Initiation of renal replacement therapy at least partially decreases signs of fluid overload; however, high blood pressure levels persist in the majority of patients after dialysis initiation. Hypervolemia due to water retention predisposes peritoneal dialysis (PD) patients to hypertension and can clinically manifest in several forms, including peripheral edema. The approaches to detect edema, which include methods such as bioimpedance, inferior vena cava diameter and biomarkers, are not always available to physicians worldwide. For clinical examinations, the presence of pitting located in the lower extremities and/or over the sacrum to diagnose the presence of peripheral edema in their patients are frequently utulized. We evaluated the impact of edema on the control of blood pressure of incident PD patients during the first year of dialysis treatment. Patients were recruited from 114 Brazilian dialysis centers that were participating in the BRAZPD study for a total of 1089 incident patients. Peripheral edema was diagnosed by the presence of pitting after finger pressure was applied to the edematous area. Patients were divided into 2 groups: those with and without edema according to the monthly medical evaluation. Blood arterial pressure, body mass index, the number of antihypertensive drugs and comorbidities were analyzed. We observed an initial BP reduction in the first five months and a stabilization of blood pressure levels from five to twelve months. The edematous group exhibited higher blood pressure levels than the group without edema during the follow-up. The results strongly indicate that the presence of a simple and easily detectable clinical sign of peripheral edema is a very relevant tool that could be used to re-evaluate not only the patient's clinical hypertensive status but also the PD prescription and patient compliance