Recurrent climate winter regimes in reconstructed and modelled 500hPa geopotential height fields over the North Atlantic/European sector 1659-1990

Recurrent climate winter regimes are examined from statistically reconstructed and modelled 500hPa geopotential height fields over the North Atlantic/European sector for the period 1659-1990. We investigate the probability density function of the state space spanned by the first two empirical orthogonal functions of combined winter data. Regimes are detected as patterns that correspond to areas of the state space with an unexpected high recurrence probability using a Monte Carlo approach. The reconstruction and the model reveal four recurrent climate regimes. They correspond to the two phases of the North Atlantic Oscillation and two opposite blocking patterns. Complemented by the investigation of the temporal evolution of the climate regimes this leads to the conclusion that the reconstructed and the modelled data for this geographic sector reproduce low-frequency atmospheric variability in the form of regime-like behaviour. The overall evidence for recurrent climate regimes is higher for the model than for the reconstruction. However, comparisons with independent data sources for the period 1659-1990 revealed a more realistic temporal evolution of the regimes for the reconstructed dat

Study protocol for Smartphone Monitoring for Atrial fibrillation in Real-Time in India (SMART-India): a community-based screening and referral programme

INTRODUCTION: Atrial fibrillation (AF), the world\u27s most common arrhythmia, often goes undetected and untreated in low-resource communities, including India, where AF epidemiology is undefined. AF is an important risk factor for stroke, which plagues an estimated 1.6 million Indians annually. As such, early detection of AF and management of high-risk patients is critically important to decrease stroke burden in individuals with AF. This study aims to describe the epidemiology of AF in Anand District, Gujarat, India, characterise the clinical profile of individuals who are diagnosed with AF and determine the performance of two mobile technologies for community-based AF screening. METHODS: This observational study builds on findings from a previous feasibility study and leverages two novel technologies as well as an existing community health programme to perform door-to-door AF screening for 2000 people from 60 villages of Anand District, Gujarat, India using local health workers. A single-lead ECG and a pulse-based application is used to screen each individual for AF three times over a period of 5 days. Participants with suspected arrhythmias are followed up by study cardiologist who makes final diagnoses. Participants diagnosed with AF are initiated on treatment based on current anticoagulation guidelines and clinical reasoning. ANALYTICAL PLAN: Age-stratified and sex-stratified prevalence of AF in the Anand District will be calculated for sample and estimated for Anand distribution using survey design weights. Sociodemographic and clinical factors associated with AF will be evaluated using multivariable regression methods. Performance of each mobile technology in detecting AF will be evaluated using a 12-lead ECG interpretation as the gold standard. ETHICS AND DISSEMINATION: This protocol was approved separately by the Institutional Review Board of University of Massachusetts Medical School and the Human Research Ethics Committee at Charutar Arogya Mandal. The findings of this study will be disseminated through peer-reviewed journals and scientific conferences

Arctic Summer Sea Ice Melt and Related Atmospheric Conditions in Coupled Regional Climate Model Simulations and Observations

Observations from 1979 to 2014 show a positive trend in the summer sea ice melt rate with an acceleration particularly in June and August. This is associated with atmospheric circulation changes such as a tendency toward a dipole pattern in the mean sea level pressure (SLP) trend with an increase over the Arctic Ocean and a decrease over Siberia. Consistent with previous studies, we here show the statistical relationship between the summer sea ice melt rate and SLP and that more than one SLP pattern is associated with anomalously high melt rates. Most high melt rates occur during high pressure over the Arctic Ocean accompanied by low pressure over Siberia, but a strong Beaufort High and advection of warm air associated with a cyclone located over the Taymyr Peninsula can also trigger anomalous high ice melt. We evaluate 10-member ensemble simulations with the coupled atmosphere-ice-ocean Arctic regional climate model HIRHAM-NAOSIM. The simulations have systematically low acceleration of sea ice melt rate in August, related to shortcomings in representing the strengthening pressure gradient from the Barents/Kara Sea toward Northern Greenland in recent decades. In general, the model shows the same classification of SLP patterns related to anomalous melt rates as the observations. However, the evolution of sea ice melt-related cloud-radiation feedback over the summer reveals contrary effects from low-level clouds in the reanalysis and in the simulations

Graph-based analysis of the metabolic exchanges between two co-resident intracellular symbionts, baumannia cicadellinicola and sulcia muelleri with their insect host, homalodisca coagulata

International audienceEndosymbiotic bacteria from different species can live inside cells of the same eukaryotic organism. Metabolic exchanges occur between host and bacteria but also between different endocytobionts. Since a complete genome annotation is available for both, we built the metabolic network of two endosymbiotic bacteria, Sulcia muelleri and Baumannia cicadellinicola, that live inside specific cells of the sharpshooter Homalodisca coagulata and studied the metabolic exchanges involving transfers of carbon atoms between the three. We automatically determined the set of metabolites potentially exogenously acquired (seeds) for both metabolic networks. We show that the number of seeds needed by both bacteria in the carbon metabolism is extremely reduced. Moreover, only three seeds are common to both metabolic networks, indicating that the complementarity of the two metabolisms is not only manifested in the metabolic capabilities of each bacterium, but also by their different use of the same environment. Furthermore, our results show that the carbon metabolism of S. muelleri may be completely independent of the metabolic network of B. cicadellinicola. On the contrary, the carbon metabolism of the latter appears dependent on the metabolism of S. muelleri, at least for two essential amino acids, threonine and lysine. Next, in order to define which subsets of seeds (precursor sets) are sufficient to produce the metabolites involved in a symbiotic function, we used a graph-based method, PITUFO, that we recently developed. Our results highly refine our knowledge about the complementarity between the metabolisms of the two bacteria and their host. We thus indicate seeds that appear obligatory in the synthesis of metabolites are involved in the symbiotic function. Our results suggest both B. cicadellinicola and S. muelleri may be completely independent of the metabolites provided by the co-resident endocytobiont to produce the carbon backbone of the metabolites provided to the symbiotic system (., thr and lys are only exploited by B. cicadellinicola to produce its proteins)

MetExplore: a web server to link metabolomic experiments and genome-scale metabolic networks

High-throughput metabolomic experiments aim at identifying and ultimately quantifying all metabolites present in biological systems. The metabolites are interconnected through metabolic reactions, generally grouped into metabolic pathways. Classical metabolic maps provide a relational context to help interpret metabolomics experiments and a wide range of tools have been developed to help place metabolites within metabolic pathways. However, the representation of metabolites within separate disconnected pathways overlooks most of the connectivity of the metabolome. By definition, reference pathways cannot integrate novel pathways nor show relationships between metabolites that may be linked by common neighbours without being considered as joint members of a classical biochemical pathway. MetExplore is a web server that offers the possibility to link metabolites identified in untargeted metabolomics experiments within the context of genome-scale reconstructed metabolic networks. The analysis pipeline comprises mapping metabolomics data onto the specific metabolic network of an organism, then applying graph-based methods and advanced visualization tools to enhance data analysis. The MetExplore web server is freely accessible at http://metexplore.toulouse.inra.fr

High Burden of Unrecognized Atrial Fibrillation in Rural India: An Innovative Community-Based Cross-Sectional Screening Program

BACKGROUND: Atrial fibrillation, the world\u27s most common arrhythmia, is a leading risk factor for stroke, a disease striking nearly 1.6 million Indians annually. Early detection and management of atrial fibrillation is a promising opportunity to prevent stroke but widespread screening programs in limited resource settings using conventional methods is difficult and costly. OBJECTIVE: The objective of this study is to screen people for atrial fibrillation in rural western India using a US Food and Drug Administration-approved single-lead electrocardiography device, Alivecor. METHODS: Residents from 6 villages in Anand District, Gujarat, India, comprised the base population. After obtaining informed consent, a team of trained research coordinators and community health workers enrolled a total of 354 participants aged 50 years and older and screened them at their residences using Alivecor for 2 minutes on 5 consecutive days over a period of 6 weeks beginning June, 2015. RESULTS: Almost two-thirds of study participants were 55 years or older, nearly half were female, one-third did not receive any formal education, and more than one-half were from households earning less than US $2 per day. Twelve participants screened positive for atrial fibrillation yielding a sample prevalence of 5.1% (95% CI 2.7-8.7). Only one participant had persistent atrial fibrillation throughout all of the screenings, and 9 screened positive only once. CONCLUSIONS: Our study suggests a prevalence of atrial fibrillation in this Indian region (5.1%) that is markedly higher than has been previously reported in India and similar to the prevalence estimates reported in studies of persons from North America and Europe. Historically low reported burden of atrial fibrillation among individuals from low and middle-income countries may be due to a lack of routine screening. Mobile technologies may help overcome resource limitations for atrial fibrillation screening in underserved and low-resource settings

Structural Sensitivity of Neural and Genetic Networks

International audienceThis paper aims at giving new results on the structural sensitivity of biological networks represented by threshold Boolean networks and ruled by Hopfield-like evolution laws classically used in the context of neural and genetic networks. Indeed, the objective is to present how certain changes and/or perturbations in such networks can modify signicantly their asymptotic behaviour. More precisely, this work has been focused on three diferent kinds of what we think to be relevant in the biological area of robustness (in both theoretical and applied frameworks): the boundary sensitivity (external fields, hormone flows, ...), the state sensitivity (axonal or somatic modulations, microRNAs actions, ...) and the updating sensitivity

Endogenous Sterol Metabolites Regulate Growth of EGFR/KRAS-Dependent Tumors via LXR

© 2015 The Authors. Meiosis-activating sterols (MAS) are substrates of SC4MOL and NSDHL in the cholesterol pathway and are important for normal organismal development. Oncogenic transformation by epidermal growth factor receptor (EGFR) or RAS increases the demand for cholesterol, suggesting a possibility for metabolic interference. To test this idea in vivo, we ablated Nsdhl in adult keratinocytes expressing KRASG12D. Strikingly, Nsdhl inactivation antagonized the growth of skin tumors while having little effect on normal skin. Loss of Nsdhl induced the expression of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, reduced the expression of low-density lipoprotein receptor (LDLR), decreased intracellular cholesterol, and was dependent on the liver X receptor (LXR) α. Importantly, EGFR signaling opposed LXRα effects on cholesterol homeostasis, whereas an EGFR inhibitor synergized with LXRα agonists in killing cancer cells. Inhibition of SC4MOL or NSDHL, or activation of LXRα by sterol metabolites, can be an effective strategy against carcinomas with activated EGFR-KRAS signaling

Changes in the annual cycle of heavy precipitation across the British Isles within the 21st century

We investigate future changes in the annual cycle of heavy daily precipitation events across the British Isles in the periods 2021–2060 and 2061–2100, relative to present day climate. Twelve combinations of regional and global climate models forced with the A1B scenario are used. The annual cycle is modelled as an inhomogeneous Poisson process with sinusoidal models for location and scale parameters of the generalized extreme value distribution. Although the peak times of the annual cycle vary considerably between projections for the 2061–2100 period, a robust shift towards later peak times is found for the south-east, while in the north-west there is evidence for a shift towards earlier peak times. In the remaining parts of the British Isles no changes in the peak times are projected. For 2021–2060 this signal is weak. The annual cycle’s relative amplitude shows no robust signal, where differences in projected changes are dominated by global climate model differences. The relative contribution of anthropogenic forcing and internal climate variability to changes in the relative amplitude cannot be identified with the available ensemble. The results might be relevant for the development of adequate risk-reduction strategies, for insurance companies and for the management and planning of water resource

Signatures of arithmetic simplicity in metabolic network architecture

Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that several of the properties predicted by the artificial chemistry model hold for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity