Adipokines and body fat composition in South Asians: results of the Metabolic Syndrome and Atherosclerosis in South Asians Living in America (MASALA) study.

ObjectiveTo investigate whether leptin and adiponectin are associated with body fat composition in a South Asian population independent of metabolic variables.DesignCross-sectional study.Subjects150 South Asian men and women, between the ages of 45-79 years, in the San Francisco Bay Area without pre-existing clinical cardiovascular disease.MeasurementsBlood samples were obtained to measure glucose metabolism variables, lipid profiles and adipokines. Total body fat was determined using dual-energy X-ray absorptiometry. Abdominal computed tomography was used to measure subcutaneous, visceral and hepatic fat.ResultsAverage body mass index (BMI) was overweight at 26.1±4.6 kg m(-2) and did not differ by sex. However, women had significantly more total body fat (P<0.001) and subcutaneous fat (P<0.001) than men, whereas men had significantly more visceral fat (P<0.001) and hepatic fat (P=0.04) than women. Women had significantly higher levels of adiponectin (P<0.01) and leptin (P<0.01). In sex-stratified analyses, leptin was strongly associated with all-body composition measures in women (P<0.05) as well as in men (P<0.05 except for hepatic fat), whereas there was an insignificant trend towards an inverse association between adiponectin and body composition in both women and men, which was significant in combined bivariate analyses. In multivariate analyses, leptin was strongly associated with all measures of adiposity, including BMI (P<0.001), total body fat (P<0.001), visceral fat (P<0.001) and hepatic fat (P=0.01). However, adiponectin's inverse association with adiposity was significantly attenuated by high-density lipoprotein (HDL), triglycerides and insulin resistance. The association between adipokines and diabetes was markedly attenuated after adjusting for body composition.ConclusionDespite only modestly elevated BMI, South Asians have elevated levels of total and regional adiposity. Leptin is strongly associated with adiposity, whereas adiponectin's association with adiposity is attenuated by metabolic variables in South Asians. Adipokines in association with adiposity have an important role in the development of diabetes

Semantic Mutation Testing for Multi-Agent Systems

This paper introduces semantic mutation testing (SMT) into multiagent systems. SMT is a test assessment technique that makes changes to the interpretation of a program and then examines whether a given test set has the ability to detect each change to the original interpretation. These changes represent possible misunderstandings of how the program is interpreted. SMT is also a technique for assessing the robustness of a program to semantic changes. This paper applies SMT to three rule-based agent programming languages, namely Jason, GOAL and 2APL, provides several contexts in which SMT for these languages is useful, and proposes three sets of semantic mutation operators (i.e., rules to make semantic changes) for these languages respectively, and a set of semantic mutation operator classes for rule-based agent languages. This paper then shows, through preliminary evaluation of our semantic mutation operators for Jason, that SMT has some potential to assess tests and program robustness

Behavioural stress responses predict environmental perception in European sea bass (Dicentrarchus labrax)

Individual variation in the response to environmental challenges depends partly on innate reaction norms, partly on experience-based cognitive/emotional evaluations that individuals make of the situation. The goal of this study was to investigate whether pre-existing differences in behaviour predict the outcome of such assessment of environmental cues, using a conditioned place preference/avoidance (CPP/CPA) paradigm. A comparative vertebrate model (European sea bass, Dicentrarchus labrax) was used, and ninety juvenile individuals were initially screened for behavioural reactivity using a net restraining test. Thereafter each individual was tested in a choice tank using net chasing as aversive stimulus or exposure to familiar conspecifics as appetitive stimulus in the preferred or non preferred side respectively (called hereafter stimulation side). Locomotor behaviour (i.e. time spent, distance travelled and swimming speed in each tank side) of each individual was recorded and analysed with video software. The results showed that fish which were previously exposed to appetitive stimulus increased significantly the time spent on the stimulation side, while aversive stimulus led to a strong decrease in time spent on the stimulation side. Moreover, this study showed clearly that proactive fish were characterised by a stronger preference for the social stimulus and when placed in a putative aversive environment showed a lower physiological stress responses than reactive fish. In conclusion, this study showed for the first time in sea bass, that the CPP/CPA paradigm can be used to assess the valence (positive vs. negative) that fish attribute to different stimuli and that individual behavioural traits is predictive of how stimuli are perceived and thus of the magnitude of preference or avoidance behaviour.European Commission [265957]; Portuguese Fundacao para a Ciencia e Tecnologia (FCT) [FRH/BPD/72952/2010]; FCT [SFRH/BD/80029/2011

Locally critical quantum phase transitions in strongly correlated metals

When a metal undergoes a continuous quantum phase transition, non-Fermi liquid behaviour arises near the critical point. It is standard to assume that all low-energy degrees of freedom induced by quantum criticality are spatially extended, corresponding to long-wavelength fluctuations of the order parameter. However, this picture has been contradicted by recent experiments on a prototype system: heavy fermion metals at a zero-temperature magnetic transition. In particular, neutron scattering from CeCu$_{6-x}$Au$_x$ has revealed anomalous dynamics at atomic length scales, leading to much debate as to the fate of the local moments in the quantum-critical regime. Here we report our theoretical finding of a locally critical quantum phase transition in a model of heavy fermions. The dynamics at the critical point are in agreement with experiment. We also argue that local criticality is a phenomenon of general relevance to strongly correlated metals, including doped Mott insulators.Comment: 20 pages, 3 figures; extended version, to appear in Natur

What have transgenic and knockout animals taught us about respiratory disease?

Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease

Stabilization of long-looped i-motif DNA by polypyridyl ruthenium complexes

A spectroscopic study of the interactions of Λ- and Δ-[Ru(phen)2(dppz)]2+ with i-motif DNA containing thymine loops of various lengths. In the presence of i-motifs, the luminescence of the Λ enantiomer was enhanced much more than the Δ. Despite this, the effect of each enantiomer on i-motif thermal stability was comparable. The sequences most affected by [Ru(phen)2(dppz)]2+ were those with long thymine loops; this suggests that long-looped i-motifs are attractive targets for potential transition metal complex drugs and should be explored further in drug design

Abscisic Acid Insensitive 4 transcription factor is an important player in the response of Arabidopsis thaliana to two-spotted spider mite (Tetranychus urticae) feeding.

Plants growing in constantly changeable environmental conditions are compelled to evolve regulatory mechanisms to cope with biotic and abiotic stresses. Effective defence to invaders is largely connected with phytohormone regulation, resulting in the production of numerous defensive proteins and specialized metabolites. In our work, we elucidated the role of the Abscisic Acid Insensitive 4 (ABI4) transcription factor in the plant response to the two-spotted spider mite (TSSM). This polyphagous mite is one of the most destructive herbivores, which sucks mesophyll cells of numerous crop and wild plants. Compared to the wild-type (Col-0) Arabidopsis thaliana plants, the abi4 mutant demonstrated increased susceptibility to TSSM, reflected as enhanced female fecundity and greater frequency of mite leaf damage after trypan blue staining. Because ABI4 is regarded as an important player in the plastid-to-nucleus retrograde signalling process, we investigated the plastid envelope membrane dynamics using stroma-associated fluorescent marker. Our results indicated a clear increase in the number of stroma-filled tubular structures deriving from the plastid membrane (stromules) in the close proximity of the site of mite leaf damage, highlighting the importance of chloroplast-derived signals in the response to TSSM feeding activity

The quest for the solar g modes

Solar gravity modes (or g modes) -- oscillations of the solar interior for which buoyancy acts as the restoring force -- have the potential to provide unprecedented inference on the structure and dynamics of the solar core, inference that is not possible with the well observed acoustic modes (or p modes). The high amplitude of the g-mode eigenfunctions in the core and the evanesence of the modes in the convection zone make the modes particularly sensitive to the physical and dynamical conditions in the core. Owing to the existence of the convection zone, the g modes have very low amplitudes at photospheric levels, which makes the modes extremely hard to detect. In this paper, we review the current state of play regarding attempts to detect g modes. We review the theory of g modes, including theoretical estimation of the g-mode frequencies, amplitudes and damping rates. Then we go on to discuss the techniques that have been used to try to detect g modes. We review results in the literature, and finish by looking to the future, and the potential advances that can be made -- from both data and data-analysis perspectives -- to give unambiguous detections of individual g modes. The review ends by concluding that, at the time of writing, there is indeed a consensus amongst the authors that there is currently no undisputed detection of solar g modes.Comment: 71 pages, 18 figures, accepted by Astronomy and Astrophysics Revie

Molecular psychiatry of zebrafish

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research

Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records

Introduction: To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Methods: Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997–2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Results: Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67–43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69–10.85]), heart failure (4.31, [3.30–5.62]), and atrial fibrillation (3.80 [3.04–4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27–2.84]) and coronary revascularisation (2.32 [1.46–3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Conclusions: Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases