Terminal Pleistocene Alaskan genome reveals first founding population of Native Americans

Despite broad agreement that the Americas were initially populated via Beringia, the land bridge that connected far northeast Asia with northwestern North America during the Pleistocene epoch, when and how the peopling of the Americas occurred remains unresolved. Analyses of human remains from Late Pleistocene Alaska are important to resolving the timing and dispersal of these populations. The remains of two infants were recovered at Upward Sun River (USR), and have been dated to around 11.5 thousand years ago (ka). Here, by sequencing the USR1 genome to an average coverage of approximately 17 times, we show that USR1 is most closely related to Native Americans, but falls basal to all previously sequenced contemporary and ancient Native Americans. As such, USR1 represents a distinct Ancient Beringian population. Using demographic modelling, we infer that the Ancient Beringian population and ancestors of other Native Americans descended from a single founding population that initially split from East Asians around 36 ± 1.5 ka, with gene flow persisting until around 25 ± 1.1 ka. Gene flow from ancient north Eurasians into all Native Americans took place 25–20 ka, with Ancient Beringians branching off around 22–18.1 ka. Our findings support a long-term genetic structure in ancestral Native Americans, consistent with the Beringian ‘standstill model’. We show that the basal northern and southern Native American branches, to which all other Native Americans belong, diverged around 17.5–14.6 ka, and that this probably occurred south of the North American ice sheets. We also show that after 11.5 ka, some of the northern Native American populations received gene flow from a Siberian population most closely related to Koryaks, but not Palaeo-Eskimos, Inuits or Kets, and that Native American gene flow into Inuits was through northern and not southern Native American groups. Our findings further suggest that the far-northern North American presence of northern Native Americans is from a back migration that replaced or absorbed the initial founding population of Ancient Beringians

Ancient Burials at Upward Sun River, Central Alaska

In the late summer about 11,500 years ago, probably in the space of a few weeks, three young Paleoindian children died and were buried in a residential camp alongside Xasaa Na’ (Upward Sun River). An infant and neonate were buried together with associated funerary objects below a central cooking hearth, and later a ~three-year-old child was cremated and buried above the same feature. This article explores the lifeways of the Ancient Beringians that summer, reconstructed through zooarchaeology, stable isotope, spatial, and artifact analyses and implications of the mortuary treatment of these individuals with respect to the regional group, theDenali Complex, and early Paleoindian ideologies

Gene set analysis exploiting the topology of a pathway

BACKGROUND: Recently, a great effort in microarray data analysis is directed towards the study of the so-called gene sets. A gene set is defined by genes that are, somehow, functionally related. For example, genes appearing in a known biological pathway naturally define a gene set. The gene sets are usually identified from a priori biological knowledge. Nowadays, many bioinformatics resources store such kind of knowledge (see, for example, the Kyoto Encyclopedia of Genes and Genomes, among others). Although pathways maps carry important information about the structure of correlation among genes that should not be neglected, the currently available multivariate methods for gene set analysis do not fully exploit it. RESULTS: We propose a novel gene set analysis specifically designed for gene sets defined by pathways. Such analysis, based on graphical models, explicitly incorporates the dependence structure among genes highlighted by the topology of pathways. The analysis is designed to be used for overall surveillance of changes in a pathway in different experimental conditions. In fact, under different circumstances, not only the expression of the genes in a pathway, but also the strength of their relations may change. The methods resulting from the proposal allow both to test for variations in the strength of the links, and to properly account for heteroschedasticity in the usual tests for differential expression. CONCLUSIONS: The use of graphical models allows a deeper look at the components of the pathway that can be tested separately and compared marginally. In this way it is possible to test single components of the pathway and highlight only those involved in its deregulation

Changes in cytokine production in healthy subjects practicing Guolin Qigong : a pilot study

BACKGROUND: Guolin Qigong is a combination of meditation, controlled breathing and physical movement designed to control the vital energy (qi) of the body and consequently to improve spiritual, physical and mental health. Practice of Qigong has been reported to alter immunological function, but there have been few studies of its effects on cytokines, the key regulators of immunity. METHODS: Numbers of peripheral blood cytokine-secreting cells were determined by ELISPOT in 19 healthy volunteers aged 27 – 55, before they were taught the practice of Qigong and after 3, 7 and 14 weeks of daily practice. The effect of Qigong on blood cortisol was also examined. RESULTS: Numbers of IL4 and IL12-secreting cells remained stable. IL6 increased at 7 weeks and TNFα increased in unstimulated cultures at 3 and 7 weeks but decreased at these times in LPS and SAC-stimulated cultures. Of particular interest, IFNγ-secreting cells increased and IL10-secreting cells decreased in PHA-stimulated cultures, resulting in significant increases in the IFNγ:IL10 ratio. Cortisol, a known inhibitor of type 1 cytokine production, was reduced by practicing Qigong. CONCLUSION: These preliminary studies in healthy subjects, although not necessarily representative of a randomized healthy population and not including a separate control group, have indicated that blood levels of the stress-related hormone cortisol may be lowered by short-term practice of Qigong and that there are concomitant changes in numbers of cytokine-secreting cells. Further studies of the effect of Qigong in patients with clinical diseases known to be associated with type 2 cytokine predominance are merited

Time-dependent effects of imatinib in human leukaemia cells: a kinetic NMR-profiling study

The goal of this study was to evaluate the time course of metabolic changes in leukaemia cells treated with the Bcr-Abl tyrosine kinase inhibitor imatinib. Human Bcr-Abl+ K562 cells were incubated with imatinib in a dose-escalating manner (starting at 0.1 μM with a weekly increase of 0.1 μM imatinib) for up to 5 weeks. Nuclear magnetic resonance spectroscopy and liquid-chromatography mass spectrometry were performed to assess a global metabolic profile, including glucose metabolism, energy state, lipid metabolism and drug uptake, after incubation with imatinib. Initially, imatinib treatment completely inhibited the activity of Bcr-Abl tyrosine kinase, followed by the inhibition of cell glycolytic activity and glucose uptake. This was accompanied by the increased mitochondrial activity and energy production. With escalating imatinib doses, the process of cell death rapidly progressed. Phosphocreatine and NAD+ concentrations began to decrease, and mitochondrial activity, as well as the glycolysis rate, was further reduced. Subsequently, the synthesis of lipids as necessary membrane precursors for apoptotic bodies was accelerated. The concentrations of the Kennedy pathway intermediates, phosphocholine and phosphatidylcholine, were reduced. After 4 weeks of exposure to imatinib, the secondary necrosis associated with decrease in the mitochondrial and glycolytic activity occurred and was followed by a shutdown of energy production and cell death. In conclusion, monitoring of metabolic changes in cells exposed to novel signal transduction modulators supplements molecular findings and provides further mechanistic insights into longitudinal changes of the mitochondrial and glycolytic pathways of oncogenesis

Maturation of Eugenia pyriformis seeds under different hydric and thermal conditions

O presente estudo tem como objetivo analisar a maturação e a dispersão de sementes de Eugenia pyriformis Cambess. produzidas em diferentes anos, verificando a influência das variações hídricas e térmicas do ambiente sobre suas características físicas e fisiológicas no momento em que são dispersas. Frutos com diferentes estágios de desenvolvimento foram coletados da região de São Paulo, entre 2003 e 2010 e das regiões de Campinas e Lavras, em 2009 e 2010 e foram analisados quanto ao tamanho e à cor. As sementes foram extraídas dos frutos e analisadas quanto ao conteúdo de massa seca, teor de água, germinação e vigor. Os resultados evidenciaram que a maturação das sementes ocorre de forma dessincronizada à maturação dos frutos, levando em média 45 dias (430 graus-dia), sendo mais demorada em períodos chuvosos ou de temperaturas mais baixas. Sementes de qualidade fisiológica mais elevada foram produzidas em anos chuvosos e quando a amplitude térmica foi maior. Conclui-se, portanto, que as variações hídricas e térmicas do ambiente e do período de formação influenciam sobre a maturação das sementes de uvaieira podendo, inclusive, determinar o ciclo de formação e a qualidade final dessas sementes.This study aims to analyze the maturation and dispersal of Eugenia pyriformis Cambess. seeds produced in different years, and the influence of variation in thermal and hydric environment on seed physical and physiological characteristics at dispersal. Fruits at different developmental stages were harvested in the city of São Paulo between 2003 and 2010, as well as in the cities of Campinas and Lavras, in 2009 and 2010 and analyzed for size and color. The seeds were extracted from the fruits and their dry mass, water content, germination and vigor were assessed. Results showed that seed maturation is unsynchronized to the maturation of the fruit, taking 45 days on average (430 growing degree-days), longer in rainy times or lower temperatures. Seeds with higher physiological quality were produced in rainy years and when the temperature range was larger. We concluded therefore that hydric and thermal environmental variations during development influence the maturation of Eugenia pyriformis seeds and are able to determine the formation cycle and the final seed quality.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Instituto de Botânica Programa de Pós-Graduação em Biodiversidade Vegetal e Meio AmbientePrataviera ConsultoriaDow AgroSciences Regulatory Sciences and Government AffairsUniversidade Estadual Paulista Instituto de Biociências Programa de Pós-Graduação em Ciências BiológicasInstituto Agronômico de Campinas Centro de Ecofisiologia e BiofísicaUniversidade Federal de Lavras (UFLA) Departamento de Ciências FlorestaisInstituto de Botânica Núcleo de Pesquisas em SementesUniversidade Estadual Paulista Instituto de Biociências Programa de Pós-Graduação em Ciências BiológicasCNPq: 477640/2009-5FAPESP: 05/04139-