Fine mapping of regulatory loci for mammalian gene expression using radiation hybrids

We mapped regulatory loci for nearly all protein-coding genes in mammals using comparative genomic hybridization and expression array measurements from a panel of mouse-hamster radiation hybrid cell lines. The large number of breaks in the mouse chromosomes and the dense genotyping of the panel allowed extremely sharp mapping of loci. As the regulatory loci result from extra gene dosage, we call them copy number expression quantitative trait loci, or ceQTLs. The -2log10P support interval for the ceQTLs was <150 kb, containing an average of <2-3 genes. We identified 29,769 trans ceQTLs with -log10P > 4, including 13 hotspots each regulating >100 genes in trans. Further, this work identifies 2,761 trans ceQTLs harboring no known genes, and provides evidence for a mode of gene expression autoregulation specific to the X chromosome.     

Refractory periods and climate forcing in cholera dynamics

Outbreaks of many infectious diseases, including cholera, malaria and dengue, vary over characteristic periods longer than 1 year. Evidence that climate variability drives these interannual cycles has been highly controversial, chiefly because it is difficult to isolate the contribution of environmental forcing while taking into account nonlinear epidemiological dynamics generated by mechanisms such as host immunity. Here we show that a critical interplay of environmental forcing, specifically climate variability, and temporary immunity explains the interannual disease cycles present in a four-decade cholera time series from Matlab, Bangladesh. We reconstruct the transmission rate, the key epidemiological parameter affected by extrinsic forcing, over time for the predominant strain (El Tor) with a nonlinear population model that permits a contributing effect of intrinsic immunity. Transmission shows clear interannual variability with a strong correspondence to climate patterns at long periods (over 7 years, for monsoon rains and Brahmaputra river discharge) and at shorter periods (under 7 years, for flood extent in Bangladesh, sea surface temperatures in the Bay of Bengal and the El Ni?o-Southern Oscillation). The importance of the interplay between extrinsic and intrinsic factors in determining disease dynamics is illustrated during refractory periods, when population susceptibility levels are low as the result of immunity and the size of cholera outbreaks only weakly reflects climate forcing.     

A whole-genome admixture scan finds a candidate locus for multiple sclerosis susceptibility

Multiple sclerosis is a common disease with proven heritability, but, despite large-scale attempts, no underlying risk genes have been identified. Traditional linkage scans have so far identified only one risk haplotype for multiple sclerosis (at HLA on chromosome 6), which explains only a fraction of the increased risk to siblings. Association scans such as admixture mapping have much more power, in principle, to find the weak factors that must explain most of the disease risk. We describe here the first high-powered admixture scan, focusing on 605 African American cases and 1,043 African American controls, and report a locus on chromosome 1 that is significantly associated with multiple sclerosis.     

Water regulation in Barmer goat of the Rajasthan desert

Summary The different body fluid compartments in normally watered and 4-day water-deprived goasts of Rajasthan desert, India, were measured in autumn. The goats maintained plasma volume and extracellular fluid volume, but lost gut and cell water considerably under the experimental conditions; indicating that the maintenance of the fluidity of the blood has priority over the body's other fluid requirements in this desert-adapted species during water deprivation.We are indebted to Dr H.S. Mann, Central Arid Zone Research Institute, Jodhpur for kindly providing the necessary facilities for this work.     

Methyl-accepting chemotaxis proteins: a core sensing element in prokaryotes and archaea

Chemotaxis is the directed motility by means of which microbes sense chemical cues and relocate towards more favorable environments. Methyl-accepting chemotaxis proteins (MCPs) are the most common receptors in bacteria and archaea. They are arranged as trimers of dimers that, in turn, form hexagonal arrays in the cytoplasmic membrane or in the cytoplasm. Several different classes of MCPs have been identified according to their ligand binding region and membrane topology. MCPs have been further classified based on the length and sequence conservation of their cytoplasmic domains. Clusters of membrane-embedded MCPs often localize to the poles of the cell, whereas cytoplasmic MCPs can be targeted to the poles or distributed throughout the cell body. MCPs play an important role in cell survival, pathogenesis, and biodegradation. Bacterial adaptation to diverse environmental conditions promotes diversity among the MCPs. This review summarizes structure, classification, and structure–activity relationship of the known MCP receptors, with a brief overview of the signal transduction mechanisms in bacteria and archaea.     

Structural and dielectric properties of doped ferrite nanomaterials suitable for microwave and biomedical applications

The sol–gel auto-combustion method was adopted to synthesize nanomaterials of single-phase X-type hexagonal ferrites with the composition of Sr2?xGdxNi2Fe28?yCdyO46 (x=0.00, 0.02, 0.04, 0.06, 0.08, 0.10 and y=0, 0.1, 0.2, 0.3, 0.4, 0.5). The structural properties were carried out by XRD analysis and the lattice parameters show variation with the doping of Gd–Cd. The average particle size measured by TEM was in the range of 8–10 nm which is beneficial in obtaining suitable signal-to-noise ratio in recording media and biomedical applications. The room temperature resistivity enhanced with the increase of the dopant concentration. The increase in resistivity indicates that the synthesized materials can be considered good for the formation of the multilayer chip inductors (MLCIs) as well as for the reduction of eddy current losses. The dielectric constant decreased with the increase in the frequency which is the general reported trend of the hexagonal ferrites and can be explained on the basis of Koop?s theory and Maxwell–Wagner polarization-model. The abnormal dielectric behavior indicates the formation of small polarons in the material. The maximum value of tangent loss at low frequencies reflects the application of these materials in medium frequency devices (MF).