Lineage Divergence and Historical Gene Flow in the Chinese Horseshoe Bat (Rhinolophus sinicus)

PMCID: PMC3581519This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Glucose and Fatty Acid Metabolism in a 3 Tissue In-Vitro Model Challenged with Normo- and Hyperglycaemia

Nutrient balance in the human body is maintained through systemic signaling between different cells and tissues. Breaking down this circuitry to its most basic elements and reconstructing the metabolic network in-vitro provides a systematic method to gain a better understanding of how cross-talk between the organs contributes to the whole body metabolic profile and of the specific role of each different cell type. To this end, a 3-way connected culture of hepatocytes, adipose tissue and endothelial cells representing a simplified model of energetic substrate metabolism in the visceral region was developed. The 3-way culture was shown to maintain glucose and fatty acid homeostasis in-vitro. Subsequently it was challenged with insulin and high glucose concentrations to simulate hyperglycaemia. The aim was to study the capacity of the 3-way culture to maintain or restore normal circulating glucose concentrations in response to insulin and to investigate the effects these conditions on other metabolites involved in glucose and lipid metabolism. The results show that the system’s metabolic profile changes dramatically in the presence of high concentrations of glucose, and that these changes are modulated by the presence of insulin. Furthermore, we observed an increase in E-selectin levels in hyperglycaemic conditions and increased IL-6 concentrations in insulin-free-hyperglycaemic conditions, indicating, respectively, endothelial injury and proinflammatory stress in the challenged 3-way system

Diagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference

BACKGROUND: Blood tests of liver injury are less well validated in non‐alcoholic fatty liver disease (NAFLD) than in patients with chronic viral hepatitis. AIMS: To improve the validation of three blood tests used in NAFLD patients, FibroTest for fibrosis staging, SteatoTest for steatosis grading and ActiTest for inflammation activity grading. METHODS: We pre‐included new NAFLD patients with biopsy and blood tests from a single‐centre cohort (FibroFrance) and from the multicentre FLIP consortium. Contemporaneous biopsies were blindly assessed using the new steatosis, activity and fibrosis (SAF) score, which provides a reliable and reproducible diagnosis and grading/staging of the three elementary features of NAFLD (steatosis, inflammatory activity) and fibrosis with reduced interobserver variability. We used nonbinary‐ROC (NonBinAUROC) as the main endpoint to prevent spectrum effect and multiple testing. RESULTS: A total of 600 patients with reliable tests and biopsies were included. The mean NonBinAUROCs (95% CI) of tests were all significant (P < 0.0001): 0.878 (0.864–0.892) for FibroTest and fibrosis stages, 0.846 (0.830–0.862) for ActiTest and activity grades, and 0.822 (0.804–0.840) for SteatoTest and steatosis grades. FibroTest had a higher NonBinAUROC than BARD (0.836; 0.820–0.852; P = 0.0001), FIB4 (0.845; 0.829–0.861; P = 0.007) but not significantly different than the NAFLD score (0.866; 0.850–0.882; P = 0.26). FibroTest had a significant difference in median values between adjacent stage F2 and stage F1 contrarily to BARD, FIB4 and NAFLD scores (Bonferroni test P < 0.05). CONCLUSIONS: In patients with NAFLD, SteatoTest, ActiTest and FibroTest are non‐invasive tests that offer an alternative to biopsy, and they correlate with the simple grading/staging of the SAF scoring system across the three elementary features of NAFLD: steatosis, inflammatory activity and fibrosis

Variation in Phenotype, Parasite Load and Male Competitive Ability across a Cryptic Hybrid Zone

BackgroundMolecular genetic studies are revealing an increasing number of cryptic lineages or species, which are highly genetically divergent but apparently cannot be distinguished morphologically. This observation gives rise to three important questions: 1) have these cryptic lineages diverged in phenotypic traits that may not be obvious to humans; 2) when cryptic lineages come into secondary contact, what are the evolutionary consequences: stable co-existence, replacement, admixture or differentiation and 3) what processes influence the evolutionary dynamics of these secondary contact zones?Methodology/principal findingsTo address these questions, we first tested whether males of the Iberian lizard Lacerta schreiberi from two highly genetically divergent, yet morphologically cryptic lineages on either side of an east-west secondary contact could be differentiated based on detailed analysis of morphology, coloration and parasite load. Next, we tested whether these differences could be driven by pre-copulatory intra-sexual selection (male-male competition). Compared to eastern males, western males had fewer parasites, were in better body condition and were more intensely coloured. Although subtle environmental variation across the hybrid zone could explain the differences in parasite load and body condition, these were uncorrelated with colour expression, suggesting that the differences in coloration reflect heritable divergence. The lineages did not differ in their aggressive behaviour or competitive ability. However, body size, which predicted male aggressiveness, was positively correlated with the colour traits that differed between genetic backgrounds.Conclusions/significanceOur study confirms that these cryptic lineages differ in several aspects that are likely to influence fitness. Although there were no clear differences in male competitive ability, our results suggest a potential indirect role for intra-sexual selection. Specifically, if lizards use the colour traits that differ between genetic backgrounds to assess the size of potential rivals or mates, the resulting fitness differential favouring western males could result in net male-mediated gene flow from west to east across the current hybrid zone.Devi Stuart-Fox, Raquel Godinho, Joëlle Goüy de Bellocq, Nancy R. Irwin, José Carlos Brito, Adnan Moussalli, Pavel Široký, Andrew F. Hugall and Stuart J. E. Bair

Assembly, organization, and function of the COPII coat

A full mechanistic understanding of how secretory cargo proteins are exported from the endoplasmic reticulum for passage through the early secretory pathway is essential for us to comprehend how cells are organized, maintain compartment identity, as well as how they selectively secrete proteins and other macromolecules to the extracellular space. This process depends on the function of a multi-subunit complex, the COPII coat. Here we describe progress towards a full mechanistic understanding of COPII coat function, including the latest findings in this area. Much of our understanding of how COPII functions and is regulated comes from studies of yeast genetics, biochemical reconstitution and single cell microscopy. New developments arising from clinical cases and model organism biology and genetics enable us to gain far greater insight in to the role of membrane traffic in the context of a whole organism as well as during embryogenesis and development. A significant outcome of such a full understanding is to reveal how the machinery and processes of membrane trafficking through the early secretory pathway fail in disease states

Internship and audit expectation gap among undergraduate students in Universiti Utara Malaysia

The accounting profession has long faced the issue of an audit expectation gap: being the gap between the quality of the profession's performance,its objectives and results, and that which the society expects.Studies have been carried out worldwide to determine the effect of education in narrowing the audit expectation gap.Extending the knowledge acquired, this paper investigates whether intership program could reduce the audit expectation gap in Malaysia.Using a pre-post method, the research instrument adapted from Ferguson el al. (2000) is administered to the UUM's accounting students before and after completing an internship program.The results show a significant change in their perceptions after the internship program.However changes in perceptions may not warrant an internship program as a means of reducing the audit expectation gap as misperceptions abaut the duties of auditors for fraud prevention and detection are still found among respondents. Nevertheless, an internship can still be used to complement audit education as it is an ideal way to expose students to professional issues and enables them to have a better insight of the actual performance and duties of auditors

Comparative Phylogeography of a Coevolved Community: Concerted Population Expansions in Joshua Trees and Four Yucca Moths

Comparative phylogeographic studies have had mixed success in identifying common phylogeographic patterns among co-distributed organisms. Whereas some have found broadly similar patterns across a diverse array of taxa, others have found that the histories of different species are more idiosyncratic than congruent. The variation in the results of comparative phylogeographic studies could indicate that the extent to which sympatrically-distributed organisms share common biogeographic histories varies depending on the strength and specificity of ecological interactions between them. To test this hypothesis, we examined demographic and phylogeographic patterns in a highly specialized, coevolved community – Joshua trees (Yucca brevifolia) and their associated yucca moths. This tightly-integrated, mutually interdependent community is known to have experienced significant range changes at the end of the last glacial period, so there is a strong a priori expectation that these organisms will show common signatures of demographic and distributional changes over time. Using a database of >5000 GPS records for Joshua trees, and multi-locus DNA sequence data from the Joshua tree and four species of yucca moth, we combined paleaodistribution modeling with coalescent-based analyses of demographic and phylgeographic history. We extensively evaluated the power of our methods to infer past population size and distributional changes by evaluating the effect of different inference procedures on our results, comparing our palaeodistribution models to Pleistocene-aged packrat midden records, and simulating DNA sequence data under a variety of alternative demographic histories. Together the results indicate that these organisms have shared a common history of population expansion, and that these expansions were broadly coincident in time. However, contrary to our expectations, none of our analyses indicated significant range or population size reductions at the end of the last glacial period, and the inferred demographic changes substantially predate Holocene climate changes