Latitudinal clines in gene expression and cis-regulatory element variation in Drosophila melanogaster

Abstract Background Organisms can rapidly adapt to their environment when colonizing a new habitat, and this could occur by changing protein sequences or by altering patterns of gene expression. The importance of gene expression in driving local adaptation is increasingly being appreciated, and cis-regulatory elements (CREs), which control and modify the expression of the nearby genes, are predicted to play an important role. Here we investigate genetic variation in gene expression in immune-challenged Drosophila melanogaster from temperate and tropical or sub-tropical populations in Australia and United States. Results We find parallel latitudinal changes in gene expression, with genes involved in immunity, insecticide resistance, reproduction, and the response to the environment being especially likely to differ between latitudes. By measuring allele-specific gene expression (ASE), we show that cis-regulatory variation also shows parallel latitudinal differences between the two continents and contributes to the latitudinal differences in gene expression. Conclusions Both Australia and United States were relatively recently colonized by D. melanogaster, and it was recently shown that introductions of both African and European flies occurred, with African genotypes contributing disproportionately to tropical populations. Therefore, both the demographic history of the populations and local adaptation may be causing the patterns that we see

Phylogenetic identification of bacterial MazF toxin protein motifs among probiotic strains and foodborne pathogens and potential implications of engineered probiotic intervention in food

BACKGROUND: Toxin-antitoxin (TA) systems are commonly found in bacteria and Archaea, and it is the most common mechanism involved in bacterial programmed cell death or apoptosis. Recently, MazF, the toxin component of the toxin-antitoxin module, has been categorized as an endoribonuclease, or it may have a function similar to that of a RNA interference enzyme. RESULTS: In this paper, with comparative data and phylogenetic analyses, we are able to identify several potential MazF-conserved motifs in limited subsets of foodborne pathogens and probiotic strains and further provide a molecular basis for the development of engineered/synthetic probiotic strains for the mitigation of foodborne illnesses. Our findings also show that some probiotic strains, as fit as many bacterial foodborne pathogens, can be genetically categorized into three major groups based on phylogenetic analysis of MazF. In each group, potential functional motifs are conserved in phylogenetically distant species, including foodborne pathogens and probiotic strains. CONCLUSION: These data provide important knowledge for the identification and computational prediction of functional motifs related to programmed cell death. Potential implications of these findings include the use of engineered probiotic interventions in food or use of a natural probiotic cocktail with specificity for controlling targeted foodborne pathogens

Exome and transcriptome sequencing of Aedes aegypti identifies a locus that confers resistance to Brugia malayi and alters the immune response.

Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait.This work was funded by a Cambridge- KAUST Academic Excellence Alliance (AEA2) project grant to AP and CVA was supported by a Cambridge Overseas Trust Studentship. JA was supported by a Darwin Trust of Edinburgh. WJP was supported by a Medical Research Council. FMJ was supported by Royal Society Research. EASIH is supported by Cambridge NIHR-BRC. The Wellcome Trust Centre for Human Genetics is funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC hub grant G0900747 91070. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.his is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100476

Adrenocortical, autonomic, and inflammatory causes of the metabolic syndrome: nested case-control study.

BACKGROUND: The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. METHODS AND RESULTS: This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (n=30) were compared with healthy controls (n=153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (+ 0.49, +0.45 SD, respectively). HRV and total power were lower among cases (both -0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (+0.89, +0.51, and +0.72 SD). Lower HRV was associated with higher normetanephrine output (r=-0.19; P=0.03). Among former cases (MS 5 years previously, n=23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences. CONCLUSIONS: Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required

Holder exponents of irregular signals and local fractional derivatives

It has been recognized recently that fractional calculus is useful for handling scaling structures and processes. We begin this survey by pointing out the relevance of the subject to physical situations. Then the essential definitions and formulae from fractional calculus are summarized and their immediate use in the study of scaling in physical systems is given. This is followed by a brief summary of classical results. The main theme of the review rests on the notion of local fractional derivatives. There is a direct connection between local fractional differentiability properties and the dimensions/ local Holder exponents of nowhere differentiable functions. It is argued that local fractional derivatives provide a powerful tool to analyse the pointwise behaviour of irregular signals and functions.Comment: 20 pages, Late

Schroedinger equation for joint bidirectional motion in time

The conventional, time-dependent Schroedinger equation describes only unidirectional time evolution of the state of a physical system, i.e., forward or, less commonly, backward. This paper proposes a generalized quantum dynamics for the description of joint, and interactive, forward and backward time evolution within a physical system. [...] Three applications are studied: (1) a formal theory of collisions in terms of perturbation theory; (2) a relativistically invariant quantum field theory for a system that kinematically comprises the direct sum of two quantized real scalar fields, such that one field evolves forward and the other backward in time, and such that there is dynamical coupling between the subfields; (3) an argument that in the latter field theory, the dynamics predicts that in a range of values of the coupling constants, the expectation value of the vacuum energy of the universe is forced to be zero to high accuracy. [...]Comment: 30 pages, no figures. Related material is in quant-ph/0404012. Differs from published version by a few added remarks on the possibility of a large-scale-average negative energy density in spac

Systemic Risk and Default Clustering for Large Financial Systems

As it is known in the finance risk and macroeconomics literature, risk-sharing in large portfolios may increase the probability of creation of default clusters and of systemic risk. We review recent developments on mathematical and computational tools for the quantification of such phenomena. Limiting analysis such as law of large numbers and central limit theorems allow to approximate the distribution in large systems and study quantities such as the loss distribution in large portfolios. Large deviations analysis allow us to study the tail of the loss distribution and to identify pathways to default clustering. Sensitivity analysis allows to understand the most likely ways in which different effects, such as contagion and systematic risks, combine to lead to large default rates. Such results could give useful insights into how to optimally safeguard against such events.Comment: in Large Deviations and Asymptotic Methods in Finance, (Editors: P. Friz, J. Gatheral, A. Gulisashvili, A. Jacqier, J. Teichmann) , Springer Proceedings in Mathematics and Statistics, Vol. 110 2015

Fluctuations in the Irreversible Decay of Turbulent Energy

A fluctuation law of the energy in freely-decaying, homogeneous and isotropic turbulence is derived within standard closure hypotheses for 3D incompressible flow. In particular, a fluctuation-dissipation relation is derived which relates the strength of a stochastic backscatter term in the energy decay equation to the mean of the energy dissipation rate. The theory is based on the so-called ``effective action'' of the energy history and illustrates a Rayleigh-Ritz method recently developed to evaluate the effective action approximately within probability density-function (PDF) closures. These effective actions generalize the Onsager-Machlup action of nonequilibrium statistical mechanics to turbulent flow. They yield detailed, concrete predictions for fluctuations, such as multi-time correlation functions of arbitrary order, which cannot be obtained by direct PDF methods. They also characterize the mean histories by a variational principle.Comment: 26 pages, Latex Version 2.09, plus seceq.sty, a stylefile for sequential numbering of equations by section. This version includes new discussion of the physical interpretation of the formal Rayleigh-Ritz approximation. The title is also change