Rise and Fall of the Beringian Steppe Bison

The widespread extinctions of large mammals at the end of the Pleistocene epoch have often been attributed to the depredations of humans; here we present genetic evidence that questions this assumption. We used ancient DNA and Bayesian techniques to reconstruct a detailed genetic history of bison throughout the late Pleistocene and Holocene epochs. Our analyses depict a large diverse population living throughout Beringia until around 37,000 years before the present, when the population’s genetic diversity began to decline dramatically. The timing of this decline correlates with environmental changes associated with the onset of the last glacial cycle, whereas archaeological evidence does not support the presence of large populations of humans in Eastern Beringia until more than 15,000 years later.   Article Summary by Jonathan C. Driver, May 2015   This article explores the movement of North American bison and the special significance of Tse’K’wa in this research, shedding insight into how the first Paleoindian peoples of Canada arrived at the land. One of the fascinating aspects about archaeology today is the speed with which new scientific techniques are developed and applied to archaeological materials. This paper demonstrates why it is so important to keep material safely stored after it has been excavated – because you never know when it will be valuable to a future researcher or when it can yield new information about the past.   Quite a few years after the excavations at Tse’K’wa were finished I was approached by Alan Cooper and Beth Shapiro of Oxford University about the possibility of sampling early bison bones from the site, to see if they still had DNA preserved. Beth was writing her doctoral thesis on the evolution of bison, and she was being supervised by Alan, a highly accomplished researcher into ancient DNA. It turned out that the Tse’K’wa bison were well preserved, and Beth was able to extract DNA and include it in the study of hundreds of samples from North America and Asia. As an added bonus, Beth and Alan arranged for radiocarbon dates to be run on every bone they studied.This added to our understanding of the age of the site\u27s earliest material.   Beth summarized her doctoral research in this paper, published in the very prestigious journal “Science”. The many contributors to her research were listed as co-authors, recognizing that each of us had contributed in a small way to the research, by sharing samples and ideas.  While the paper mainly deals with Beth’s conclusions about the evolutionary history of bison, for those interested in Tse’K’wa and the history of the early peoples of Canada, there was a fascinating tidbit of information contained in the Tse’K’wa bison DNA – they were from two quite distinct populations.   To understand the significance of this, we must first consider the impact of the extensive ice sheets that formed across Canada about 20,000 years ago. The ice sheets separated North American bison into two populations. One group of bison herds lived to the south of the ice sheets, in what is today, the continental USA and very southern parts of Saskatchewan, Alberta and B.C. The other population lived in unglaciated regions of, what is today, Yukon, Alaska and northeast Asia. These two populations can be distinguished by minor differences in their DNA. When Beth studied the bison fossils from across the vast region of their ice-age distribution she found that in every location except one the bison were either northern or southern types. The one exception was Tse’K’wa where bison from both the north and south were found.   The explanation for this seems fairly straightforward. When the western Canadian ice sheets melted and new pastures were developed, northern bison began to move south through the Yukon and into northern and central BC and Alberta. At the same time, the southern bison began to move north, also following pastures that developed on the recently de-glaciated  landcapes.  Finally, the northern and southern populations met in the Peace River region. There is no evidence that they bred with each other, and, based on the genetics of modern bison in North America it appears that the southern form survived and evolved into the bison we are familiar with today.   The Tse’K’wa data suggest the meeting of bison populations must have occurred around the same time the site was first occupied by humans, as it is very unlikely that two genetically distinct populations of bison could have lived in the same environment without interbreeding or one of them becoming extinct. This means the establishment of a viable migration route for animals (and people) from Alaska through Yukon, B.C., Alberta and into continental USA must have happened after the dates of the earliest human presence in the continental USA and South America. Therefore, the first people to enter North America could not have migrated through an ice-free corridor along the eastern slopes of the Rockies. Assuming they entered the Americas during the last ice age, then the most likely route would be down the coast of Alaska and British Columbia. Interestingly, this hypothesis was proposed by the director of the 1983 Tse’K’wa excavations, Knut Fladmark, in a paper published in 1979!   The Tse’K’wa stone artifacts lend support to this scenario. The earliest spear point at the site – the “fluted point” – is stylistically very similar to artifacts found in the south, which date a little earlier than those at Tse’K’wa. This supports the notion that the earliest inhabitants of the site were part of a human population that began to move north (perhaps out of southern Alberta and northern Montana)  following the bison herds as they moved north to exploit the newly created grassland environments that formed as ice melted and glacial lakes drained away

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Parental knowledge of paediatric vaccination

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher

Light cone effect on the reionization 21-cm signal – II. Evolution, anisotropies and observational implications

Measurements of the H I 21-cm power spectra from the reionization epoch will be influenced by the evolution of the signal along the line-of-sight direction of any observed volume. We use numerical as well as seminumerical simulations of reionization in a cubic volume of 607 Mpc across to study this so-called light-cone effect on the H I 21-cm power spectrum. We find that the light-cone effect has the largest impact at two different stages of reionization: one when reionization is ∼20 per cent and other when it is ∼80 per cent completed. We find a factor of ∼4 amplification of the power spectrum at the largest scale available in our simulations. We do not find any significant anisotropy in the 21-cm power spectrum due to the light-cone effect. We argue that for the power spectrum to become anisotropic, the light-cone effect would have to make the ionized bubbles significantly elongated or compressed along the line of sight, which would require extreme reionization scenarios. We also calculate the two-point correlation functions parallel and perpendicular to the line of sight and find them to differ. Finally, we calculate an optimum frequency bandwidth below which the light-cone effect can be neglected when extracting power spectra from observations. We find that if one is willing to accept a 10 per cent error due to the light-cone effect, the optimum frequency bandwidth for k = 0.056 Mpc−1 is ∼7.5 MHz. For k = 0.15 and 0.41 Mpc−1, the optimum bandwidth is ∼11 and ∼16 MHz, respectively

Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note: updated version of arXiv:gr-qc/050809

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Predictors of unintended pregnancy in Kersa, Eastern Ethiopia, 2010

<p>Abstract</p> <p>Background</p> <p>In Ethiopia, little is known about pregnancy among rural women. Proper maternal health care depends on clear understanding of the reproductive health situation. The objective of this study was to identify predictors of unintended pregnancy in rural eastern Ethiopia.</p> <p>Methodology</p> <p>This study was part of pregnancy surveillance at Kersa Demographic Surveillance and Health Research Center, East Ethiopia. Pregnant women were assessed whether their current pregnancy was intended or not. Data were collected by lay interviewers using uniform questionnaire. Odds Ratio, with 95% confidence interval using multiple and multinomial logistic regression were calculated to detect level of significance.</p> <p>Results</p> <p>Unintended pregnancy was reported by 27.9% (578/2072) of the study subjects. Out of which, 440 were mistimed and 138 were not wanted. Unintended pregnancy was associated with family wealth status (OR 1.47; 95% CI 1.14, 1.90), high parity (7 +) (OR 5.18; 95% CI 3.31, 8.12), and a longer estimated time to walk to the nearest health care facility (OR 2.24; 95% CI: 1.49, 3.39).</p> <p>In the multinomial regression, women from poor family reported that their pregnancy was mistimed (OR 1.69; 95% CI 1.27, 2.25). The longer estimated time (80 + minutes) to walk to the nearest health care facility influenced the occurrence of mistimed pregnancy (OR 2.58; 95% CI: 1.65, 4.02). High parity (7+) showed a strong association to mistimed and unwanted pregnancies (OR 3.11; 95% CI 1.87, 5.12) and (OR 14.34; 95% CI 5.72, 35.98), respectively.</p> <p>Conclusions</p> <p>The economy of the family, parity, and walking distance to the nearest health care institution are strong predictors of unintended pregnancy. In order to reduce the high rate of unintended pregnancy Efforts to reach rural women with family planning services should be strengthened.</p