Reconstructing Native American population history

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.     

Long‐Run and Cyclical Dynamics in the US Stock Market

This paper uses fractional integration to examine the long‐run dynamics and cyclical structure of US inflation, real risk‐free rate, real stock returns, equity premium and price/dividend ratio, annually from 1871 to 2000. It implements a procedure which allows consideration of unit roots with possibly fractional orders of integration both at zero (long‐run) and cyclical frequencies. When focusing exclusively on the former, the estimated order of integration varies considerably, and non‐stationarity is found only for the price/dividend ratio. When the cyclical component is also taken into account, the series appear to be stationary but to exhibit long memory with respect to both components in almost all cases. The exception is the price/dividend ratio, whose order of integration is higher than 0.5 but smaller than 1 for the long‐run frequency, and is between 0 and 0.5 for the cyclical component. Also, mean reversion occurs in all cases. Finally, six different criteria are applied to compare the forecasting performance of the fractional (at both zero and cyclical frequencies) models with others based on fractional and integer differentiation only at the zero frequency. The results, based on a 15‐year horizon, show that the former outperforms the others in a number of cases. Copyright © 2013 John Wiley & Sons, Ltd.     

Temporal dynamics of invertebrate and aquatic plant communities at three intermittent ponds in livestock grazed Patagonian wetlands

Ponds are recognized worldwide as biodiversity hotspots; nevertheless in Patagonia studies are still needed that reveal the composition and status of their communities. This paper analyses the temporal patterns of aquatic invertebrates and assesses the environmental factors that best predict the variation in community structure at three small intermittent ponds, subjected to ranching practices (summer stocking) in the Patagonian steppe. Variables identified as important in structuring community assemblages were related to environmental conditions (rainfall and water temperature), chemical features (conductivity and pH) and biotic factors (macrophyte coverage). During the connected phase only a small number of invertebrate species were present, in contrast to the 11 taxa that were frequent and abundant during the isolated period (Eucyclops chilensis, Hyalella curvispina and Rhionaeschna sp. were dominant). In this sequence the submersed Myriophyllum quitense and Lilaeopsis macloviana played a crucial role offering habitat and food resources. The present study provides valuable information that can contribute to minimizing the environmental damage and the development of strategies for the conservation of Patagonian wetlands.     

CFTR pharmacology

CFTR protein is an ion channel regulated by cAMP-dependent phosphorylation and expressed in many types of epithelial cells. CFTR-mediated chloride and bicarbonate secretion play an important role in the respiratory and gastrointestinal systems. Pharmacological modulators of CFTR represent promising drugs for a variety of diseases. In particular, correctors and potentiators may restore the activity of CFTR in cystic fibrosis patients. Potentiators are also potentially useful to improve mucociliary clearance in patients with chronic obstructive pulmonary disease. On the other hand, CFTR inhibitors may be useful to block fluid and electrolyte loss in secretory diarrhea and slow down the progression of polycystic kidney disease.     

Paul Ehrenfest: The Genesis of the Adiabatic Hypothesis, 1911–1914

We analyze the evolution of EHRENFEST's thought since he proved the necessity of quanta in 1911 until the formulation of his adiabatic hypothesis in 1914. We argue that his research contributed significantly to the solution of critical problems in quantum physics and led to a rigorous definition of the range of validity of BOLTZMANN's principle.     

Neural substrates of awakening probed with optogenetic control of hypocretin neurons

The neural underpinnings of sleep involve interactions between sleep-promoting areas such as the anterior hypothalamus, and arousal systems located in the posterior hypothalamus, the basal forebrain and the brainstem. Hypocretin (Hcrt, also known as orexin)-producing neurons in the lateral hypothalamus are important for arousal stability, and loss of Hcrt function has been linked to narcolepsy. However, it is unknown whether electrical activity arising from Hcrt neurons is sufficient to drive awakening from sleep states or is simply correlated with it. Here we directly probed the impact of Hcrt neuron activity on sleep state transitions with in vivo neural photostimulation, genetically targeting channelrhodopsin-2 to Hcrt cells and using an optical fibre to deliver light deep in the brain, directly into the lateral hypothalamus, of freely moving mice. We found that direct, selective, optogenetic photostimulation of Hcrt neurons increased the probability of transition to wakefulness from either slow wave sleep or rapid eye movement sleep. Notably, photostimulation using 5-30 Hz light pulse trains reduced latency to wakefulness, whereas 1 Hz trains did not. This study establishes a causal relationship between frequency-dependent activity of a genetically defined neural cell type and a specific mammalian behaviour central to clinical conditions and neurobehavioural physiology.     

Zinc bioleaching from an iron concentrate using <Emphasis Type="Italic">Acidithiobacillus ferrooxidans</Emphasis> strain from Hercules Mine of Coahuila,Mexico

The iron concentrate from Hercules Mine of Coahuila, Mexico, which mainly contained pyrite and pyrrhotite, was treated by the bioleaching process using native strain Acidithiobacillus ferrooxidans (A. ferrooxidans) to determine the ability of these bacteria on the leaching of zinc. The native bacteria were isolated from the iron concentrate of the mine. The bioleaching experiments were carried out in shake flasks to analyze the effects of pH values, pulp density, and the ferrous sulfate concentration on the bioleaching process. The results obtained by microbial kinetic analyses for the evaluation of some aspects of zinc leaching show that the native bacteria A. ferrooxidans, which is enriched with a 9K Silverman medium under the optimum conditions of pH 2.0, 20 g/L pulp density, and 40 g/L FeSO₄, increases the zinc extraction considerably observed by monitoring during15 d, i.e., the zinc concentration has a decrease of about 95% in the iron concentrate.     

EphB-ephrin-B interactions suppress colorectal cancer progression by compartmentalizing tumor cells

The genes encoding tyrosine kinase receptors EphB2 and EphB3 are beta-catenin and Tcf4 target genes in colorectal cancer (CRC) and in normal intestinal cells. In the intestinal epithelium, EphB signaling controls the positioning of cell types along the crypt-villus axis. In CRC, EphB activity suppresses tumor progression beyond the earliest stages. Here we show that EphB receptors compartmentalize the expansion of CRC cells through a mechanism dependent on E-cadherin-mediated adhesion. We demonstrate that EphB-mediated compartmentalization restricts the spreading of EphB-expressing tumor cells into ephrin-B1-positive territories in vitro and in vivo. Our results indicate that CRC cells must silence EphB expression to avoid repulsive interactions imposed by normal ephrin-B1-expressing intestinal cells at the onset of tumorigenesis.     

A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21

Much of the variation in inherited risk of colorectal cancer (CRC) is probably due to combinations of common low risk variants. We conducted a genome-wide association study of 550,000 tag SNPs in 930 familial colorectal tumor cases and 960 controls. The most strongly associated SNP (P = 1.72 x 10(-7), allelic test) was rs6983267 at 8q24.21. To validate this finding, we genotyped rs6983267 in three additional CRC case-control series (4,361 affected individuals and 3,752 controls; 1,901 affected individuals and 1,079 controls; 1,072 affected individuals and 415 controls) and replicated the association, providing P = 1.27 x 10(-14) (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16-1.39) and 1.47 (95% c.i.: 1.34-1.62) for heterozygotes and rare homozygotes, respectively. Analyses based on 1,477 individuals with colorectal adenoma and 2,136 controls suggest that susceptibility to CRC is mediated through development of adenomas (OR = 1.21, 95% c.i.: 1.10-1.34; P = 6.89 x 10(-5)). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia.