Genome-scale phylogenetic analysis finds extensive gene transfer among Fungi

Although the role of lateral gene transfer is well recognized in the evolution of bacteria, it is generally assumed that it has had less influence among eukaryotes. To explore this hypothesis we compare the dynamics of genome evolution in two groups of organisms: Cyanobacteria and Fungi. Ancestral genomes are inferred in both clades using two types of methods. First, Count, a gene tree unaware method that models gene duplications, gains and losses to explain the observed numbers of genes present in a genome. Second, ALE, a more recent gene tree-aware method that reconciles gene trees with a species tree using a model of gene duplication, loss, and transfer. We compare their merits and their ability to quantify the role of transfers, and assess the impact of taxonomic sampling on their inferences. We present what we believe is compelling evidence that gene transfer plays a significant role in the evolution of Fungi

Design of a Thermally-Actuated Gas Lift Safety Valve

Gas-lifted oil wells are susceptible to failure through malfunction of gas lift valve assemblies (GLV). One failure mode occurs when the GLV check valve fails and product passes into the well annulus, potentially reaching the wellhead. This is a growing concern as offshore wells are drilled thousands of meters below the ocean floor in extreme temperature and pressure conditions, and repair and monitoring become difficult. Currently no safeguard exists in the GLV to prevent product passage in the event of check valve failure. In this paper a design and operational procedures are proposed for a thermally-actuated positive-locking safety valve to seal the GLV in the event of check valve failure. A thermal model of the well and GLV system is developed and compared to well data to verify feasibility of a thermally-actuated safety valve. A 3× scale prototype safety valve is built and tested under simulated failure scenarios and well start-up scenarios. Realistic well temperatures in the range of 20C to 70C are used. Results demonstrate valve closure in response to simulated check valve failure and valve opening during simulated well start-up

dh+CU: Future Directions for Digital Humanities at CU Boulder

Digital Humanities (DH) work harnesses digital technologies to disseminate, analyze and synthesize information in new and innovative ways, often to answer humanistic questions, and may make use of tools like visualization, text mining and statistical tools. The Libraries’ Digital Humanities Task Force was formed to investigate and report on DH activities and needs on campus and formulate recommendations for how the Libraries might help support these needs in tandem with campus partners. We take a broad view of DH and were as inclusive as possible in all of these activities – the disciplinary affiliation of the scholar engaging in these activities (humanities, social sciences or sciences) is irrelevant. In this context, DH is not a circumscribed concept but rather a broad set of methodologies and approaches that loom large in the realm of support and participation libraries and their staff can offer to users undertaking digital scholarship. The Task Force undertook several major activities to meet these goals. Among them are: an investigation of library-associated DH initiatives at other institutions; an environmental scan of campus facilities and services; a campus-wide survey (345 responses); in-depth interviews with 20 faculty, graduate students and other campus researchers; additional interviews with those involved in external DH initiatives; and presentations and feedback during the DH symposium and workshop held in August 2013. Our research showed that DH work was of broad interest to graduate students and faculty on campus across disciplinary boundaries

Hot but Not Dry: Modest Changes in Water Relations for an Epiphytic Bromeliad in a Tropical Dry Deciduous Forest

Premise of research. Epiphytic bromeliads endure intense seasonal environmental changes in the canopy of dry tropical deciduous forests. The analysis of the physiological responses of these epiphytes to environmental changes can be useful in assessing their plasticity, vulnerability, and adaptations to such extreme habitats. Methodology. We measured microenvironmental variables and water relations for plants of the epiphytic bromeliad Tillandsia brachycaulos in three microhabitats within the canopy of a dry tropical forest. We measured individual plants for seasonal and spatial differences in light, leaf temperature, osmotic potential, cell wall elasticity, and relative capacitance as indications of their physiological responses to the changing environment. Pivotal results. We detected greater physiological differences for leaves of T. brachycaulos among seasons than among microhabitats. Osmotic potential decreased in the early dry season, especially in the low and middle strata within the canopy, and leaf relative capacitance increased. Conclusions. Individuals of T. brachycaulos displayed modest leaf physiological responses to the strong seasonal environmental changes within the canopy of this tropical forest. Such responses are in agreement with the observation that when water is available, it has high water potential, and thus water storage is the main strategy for surviving in such extreme conditions

Contrasting Male and Female Dietary Life Histories: A Case Study at an Ancestral Muwekma Ohlone Heritage Site in San Jose, California

Stable carbon and nitrogen isotope analyses of bones and teeth at the ancestral heritage Muwekma Ohlone site of Yakmuy ‘Ooyákma-tka (“Place of the East Ridge Site”; CA-SCL-215) reveal significant differences in the dietary life history of males and females. Overall, isotope data indicate that site inhabitants were primarily dependent on low trophic-level foods, likely plants, and minor amounts of marine food for their main source of dietary protein. From tooth dentin serial samples, we found that males were elevated by 0.6-1.0‰ in δ15N in early childhood (age 1-9 years) relative to females, while δ13C values were similar by sex, indicating boys were accessing slightly greater amounts of higher trophic-level foods, such as meat from game. The sex-biased difference in δ15N diminishes during the second decade of life, as female δ15N values increase and become equal to males. However, a difference in δ13C emerges during the second decade where female δ13C values are elevated relative to males. This could indicate that teenage females consumed higher amounts of low trophic-level, marine-derived protein, such as shellfish. During later adult years, the difference in δ13C disappears, while males again show an increase in δ15N relative to females. Although these differences are small, they reveal important sex-biased life history patterns during childhood and adulthood in this ancient community

Validation of the Nasa Integrated Medical Model: a Space Flight Medical Risk Prediction Tool

The Human Research Program funded the development of the Integrated Medical Model (IMM) to quantify the medical component of overall mission risk. The IMM uses Monte Carlo simulation methodology, incorporating space flight and ground medical data, to estimate the probability of mission medical outcomes and resource utilization. To determine the credibility of IMM output, the IMM project team completed two validation studies that compared IMM predicted output to observed medical events from a selection of Shuttle Transportation System (STS) and International Space Station (ISS) missions. The validation study results showed that the IMM underpredicted the occurrence of ~10% of the modeled medical conditions for the STS missions and overpredicted ~20% of the modeled medical conditions for the ISS missions. These findings imply that the strength of IMM predictions to inform decisions depends on simulated mission specifications including length. This discrepancy could result from medical recording differences between ISS and STS that possibly influence observed incidence rates, IMM combining all "mission type" data as constant occurrence rate or fixed proportion across both mission types, misspecification of symptoms to conditions, and gaps in the literature informing the model. Some of these issues will be alleviated by updating the IMM source data through incorporation of the observed validation data

PRMT5-Selective Inhibitors Suppress Inflammatory T Cell Responses and Experimental Autoimmune Encephalomyelitis

In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cell–mediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking. PRMT5 is the main PRMT responsible for symmetric dimethylation of arginine residues of histones and other proteins. PRMT5 drives embryonic development and cancer, but its role in T cells, if any, has not been investigated. In this article, we show that PRMT5 is an important modulator of CD4+ T cell expansion. PRMT5 was transiently upregulated during maximal proliferation of mouse and human memory Th cells. PRMT5 expression was regulated upstream by the NF-κB pathway, and it promoted IL-2 production and proliferation. Blocking PRMT5 with novel, highly selective small molecule PRMT5 inhibitors severely blunted memory Th expansion, with preferential suppression of Th1 cells over Th2 cells. In vivo, PRMT5 blockade efficiently suppressed recall T cell responses and reduced inflammation in delayed-type hypersensitivity and clinical disease in EAE mouse models. These data implicate PRMT5 in the regulation of adaptive memory Th cell responses and suggest that PRMT5 inhibitors may be a novel therapeutic approach for T cell–mediated inflammatory disease

Studying the Boundary Layer Late Afternoon nd Sunset Turbulence (BLLAST)

At the end of the afternoon, when the surface heat fluxes start to sharply decrease, the CBL turns from a convective well-mixed layer to an intermittently turbulent residual layer overlying a stably-stratified boundary layer. This transition raises several observational and modeling issues. Even the definition of the boundary layer during this period is fuzzy, since there is no consensus on what criteria to use and no simple scaling laws to apply. Yet it plays an important role in such diverse atmospheric phenomena as transport and diffusion of trace constituents or wind energy production. This phase of the diurnal cycle remains largely unexplored, partly due to the difficulty of measuring weak and intermittent turbulence, anisotropy, horizontal heterogeneity, and rapid time changes. The Boundary Layer Late Afternoon and Sunset Turbulence (BLLAST) project is gathering about thirty research scientists from the European Union and the United States to work on this issue. A field campaign (BLLAST-FE) is planned for spring or summer 2011 in Europe. BLLAST will utilize these observations, as well as previous datasets, large-eddy and direct numerical simulations, and mesoscale modeling to better understand the processes, suggest new parameterizations, and evaluate forecast models during this transitional period. We will present the issues raised by the late afternoon transition and our strategy to study it.Peer ReviewedPostprint (published version

Interferon-gamma ameliorates experimental autoimmune encephalomyelitis by inducing homeostatic adaptation of microglia

Compelling evidence has shown that interferon (IFN)-γ has dual effects in multiple sclerosis and in its animal model of experimental autoimmune encephalomyelitis (EAE), with results supporting both a pathogenic and beneficial function. However, the mechanisms whereby IFN-γ may promote neuroprotection in EAE and its effects on central nervous system (CNS)-resident cells have remained an enigma for more than 30 years. In this study, the impact of IFN-γ at the peak of EAE, its effects on CNS infiltrating myeloid cells (MC) and microglia (MG), and the underlying cellular and molecular mechanisms were investigated. IFN-γ administration resulted in disease amelioration and attenuation of neuroinflammation associated with significantly lower frequencies of CNS CD11b+ myeloid cells and less infiltration of inflammatory cells and demyelination. A significant reduction in activated MG and enhanced resting MG was determined by flow cytometry and immunohistrochemistry. Primary MC/MG cultures obtained from the spinal cord of IFN-γ-treated EAE mice that were ex vivo re-stimulated with a low dose (1 ng/ml) of IFN-γ and neuroantigen, promoted a significantly higher induction of CD4+ regulatory T (Treg) cells associated with increased transforming growth factor (TGF)-β secretion. Additionally, IFN-γ-treated primary MC/MG cultures produced significantly lower nitrite in response to LPS challenge than control MC/MG. IFN-γ-treated EAE mice had a significantly higher frequency of CX3CR1high MC/MG and expressed lower levels of program death ligand 1 (PD-L1) than PBS-treated mice. Most CX3CR1highPD-L1lowCD11b+Ly6G- cells expressed MG markers (Tmem119, Sall2, and P2ry12), indicating that they represented an enriched MG subset (CX3CR1highPD-L1low MG). Amelioration of clinical symptoms and induction of CX3CR1highPD-L1low MG by IFN-γ were dependent on STAT-1. RNA-seq analyses revealed that in vivo treatment with IFN-γ promoted the induction of homeostatic CX3CR1highPD-L1low MG, upregulating the expression of genes associated with tolerogenic and anti-inflammatory roles and down-regulating pro-inflammatory genes. These analyses highlight the master role that IFN-γ plays in regulating microglial activity and provide new insights into the cellular and molecular mechanisms involved in the therapeutic activity of IFN-γ in EAE