Automated Isolation of Translational Efficiency Bias that Resists the Confounding Effect of GC(AT)-Content

Genomic sequencing projects are an abundant source of information for biological studies ranging from the molecular to the ecological in scale; however, much of the information present may yet be hidden from casual analysis. One such information domain, trends in codon usage, can provide a wealth of information about an organism\u27s genes and their expression. Degeneracy in the genetic code allows more than one triplet codon to code for the same amino acid, and usage of these codons is often biased such that one or more of these synonymous codons is preferred. Detection of this bias is an important tool in the analysis of genomic data, particularly as a predictor of gene expressivity. Methods for identifying codon usage bias in genomic data that rely solely on genomic sequence data are susceptible to being confounded by the presence of several factors simultaneously influencing codon selection. Presented here is a new technique for removing the effects of one of the more common confounding factors, GC(AT)-content, and of visualizing the search-space for codon usage bias through the use of a solution landscape. This technique successfully isolates expressivity-related codon usage trends, using only genomic sequence information, where other techniques fail due to the presence of GC(AT)-content confounding influences

Cross-Presentation of a Spread-Defective MCMV Is Sufficient to Prime the Majority of Virus-Specific CD8+ T Cells

CD8+ T cells can be primed by peptides derived from endogenous proteins (direct presentation), or exogenously acquired protein (cross-presentation). However, the relative ability of these two pathways to prime CD8+ T cells during a viral infection remains controversial. Cytomegaloviruses (CMVs) can infect professional antigen presenting cells (APCs), including dendritic cells, thus providing peptides for direct presentation. However, the viral immune evasion genes profoundly impair recognition of infected cells by CD8+ T cells. Nevertheless, CMV infection elicits a very strong CD8+ T cell response, prompting its recent use as a vaccine vector. We have shown previously that deleting the immune evasion genes from murine cytomegalovirus (MCMV) that target class I MHC presentation, has no impact on the size or breadth of the CD8+ T cell response elicited by infection, suggesting that the majority of MCMV-specific CD8+ T cells in vivo are not directly primed by infected professional APCs. Here we use a novel spread-defective mutant of MCMV, lacking the essential glycoprotein gL, to show that cross-presentation alone can account for the majority of MCMV-specific CD8+ T cell responses to the virus. Our data support the conclusion that cross-presentation is the primary mode of antigen presentation by which CD8+ T cells are primed during MCMV infection

Intermediate mass stars: updated models

A new set of stellar models in the mass range 1.2 to 9 $M_{\odot}$ is presented. The adopted chemical compositions cover the typical galactic values, namely $0.0001 \le Z \le 0.02$ and $0.23 \le Y \le 0.28$. A comparison among the most recent compilations of similar stellar models is also discussed. The main conclusion is that the differencies among the various evolutionary results are still rather large. For example, we found that the H-burning evolutionary time may differ up to 20 %. An even larger disagreement is found for the He-burning phase (up to 40-50 %). Since the connection between the various input physics and the numerical algorithms could amplify or counterbalance the effect of a single ingredient on the resulting stellar model, the origin of this discrepancies is not evident. However most of these discrepancies, which are clearly found in the evolutionary tracks, are reduced on the isochrones. By means of our updated models we show that the ages inferred by the theory of stellar evolution is in excellent agreement with those obtained by using other independent methods applied to the nearby Open Clusters. Finally, the theoretical initial/final mass relation is revised.Comment: 35 pages, 24 figures, 4 tables, accepted for publication in the Astrophisycal Journa

Sensitive Periods for Psychosocial Risk in Childhood and Adolescence and Cardiometabolic Outcomes in Young Adulthood

Greater psychosocial risk in childhood and adolescence predicts poorer cardiometabolic outcomes in adulthood. We assessed whether the timing of psychosocial risk from infancy through adolescence predicts cardiometabolic outcomes in young adulthood. Young adults and their mothers participated in a longitudinal study beginning in infancy in Santiago, Chile (N = 1040). At infancy, 5 years, 10 years, and adolescence, mothers reported on depressive symptoms, stressful experiences, support for child development in the home, father absence, parental education, and socioeconomic status (SES) to create a psychosocial risk composite at each time point. Young adults (52.1% female; 21–27 years) provided fasting serum samples and participated in anthropometric and blood pressure (BP) assessments, including a dualenergy X-ray absorptiometry (DXA) scan for measuring body fat. Greater infant psychosocial risk was associated with a greater young adult metabolic syndrome score (β = 0.07, 95% confidence intervals (CI): 0.01 to 0.13, p = 0.02), a higher body mass index and waist circumference composite (β = 0.08, 95% CI: 0.03 to 0.13, p = 0.002), and a higher body fat (DXA) composite (β = 0.07, 95% CI: 0.01 to 0.12, p = 0.02). No psychosocial risk measure from any time point was associated with BP. Infant psychosocial risk predicted cardiometabolic outcomes in young adulthood better than psychosocial risk at 5 years, 10 years, or adolescence, mean of psychosocial risk from infancy through adolescence, and maximum of psychosocial risk at any one time. Consistent with the Developmental Origins of Health and Disease model, findings suggest that infancy is a sensitive period for psychosocial risk leading to poorer cardiometabolic outcomes in young adulthood

Mass-luminosity relation and pulsational properties of Wolf-Rayet stars

Evolution of Population I stars with initial masses from 70M_\odot to 130M_\odot is considered under various assumptions on the mass loss rate \dot M. The mass-luminosity relation of W-R stars is shown to be most sensitive to the mass loss rate during the helium burning phase \dot M_{3\alpha}. Together with the mass-luminosity relation obtained for all evolutionary sequences several more exact relations are determined for the constant ratio f_{3\alpha}=\dot M/\dot M_{3\alpha} with 0.5 \le f_{3\alpha} \le 3. Evolutionary models of W-R stars were used as initial conditions in hydrodynamic computations of radial nonlinear stellar oscillations. The oscillation amplitude is larger in W-R stars with smaller initial mass or with lower mass loss rate due to higher surface abundances of carbon and oxygen. In the evolving W-R star the oscillation amplitude decreases with decreasing stellar mass M and for M < 10M_\odot the sufficiently small nonlinear effects allow us to calculate the integral of the mechanical work W done over the pulsation cycle in each mass zone of the hydrodynamical model. The only positive maximum on the radial dependence of W is in the layers with temperature of T\sim 2e5K where oscillations are excited by the iron Z--bump kappa-mechanism. Radial oscillations of W-R stars with mass of M > 10M_\odot are shown to be also excited by the kappa-mechanism but the instability driving zone is at the bottom of the envelope and pulsation motions exist in the form of nonlinear running waves propagating outward from the inner layers of the envelope.Comment: 15 pages, 10 figures, submitted to Astronomy Letter

Vacuum Chamber Design of NSLS-II Storage Ring

National Synchrotron Light Source II (NSLS II) will be a 3-GeV, 792-meter circumference, 3rd generation synchrotron radiation facility, with ultra low emittance and extremely high brightness. the storage ring has 30 Double-Bend-Achromatic (DBA) cells. in each cell, there are five magnets and chamber girders, and one straight section for insertion devices or Radio Frequency (RF) cavities or injection. Most vacuum chambers are made from extruded aluminum with two different cross sections: one fitted in the dipole magnets, and the other surrounded by multipole magnets. They discuss the layout of the DBA cells, the detailed design of the cell's vacuum chambers, the mounting of the Beam-Position-Monitor (BPM) buttons, discrete absorbers, lumped pumps and the distributed Non-Evaporable Getter (NEG) strips, and describe the fabrication and testing of these prototype cell chambers. The account also details the development of the chamber bakeout process, the NEG stri's supports, and the RF shielded bellows

Family conflict, chaos, and negative life events predict cortisol activity in low‐income children

Childhood poverty is hypothesized to increase risk for mental and physical health problems at least in part through dysregulation of the hypothalamic‐pituitary‐adrenal axis. However, less is known about the specific psychosocial stressors associated with cortisol reactivity and regulation for children living in poverty. The current study investigates negative life events, household chaos, and family conflict in preschool and middle childhood as potential predictors of cortisol regulation in low‐income 7–10 year olds (N = 242; M age = 7.9 years). Participants were assessed in preschool and participated in a follow‐up assessment in middle childhood, during which diurnal free cortisol and free cortisol reactivity to the Trier Social Stress Test for Children (TSST‐C) were assessed. Household chaos during preschool predicted a more blunted diurnal cortisol slope in middle childhood. Greater negative life events during preschool and greater concurrent family conflict were associated with increased free cortisol reactivity in middle childhood.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144279/1/dev21602_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144279/2/dev21602.pd

Diversity of Murine Norovirus Strains Isolated from Asymptomatic Mice of Different Genetic Backgrounds within a Single U.S. Research Institute

Antibody prevalence studies in laboratory mice indicate that murine norovirus (MNV) infections are common, but the natural history of these viruses has not been fully established. This study examined the extent of genetic diversity of murine noroviruses isolated from healthy laboratory mice housed in multiple animal facilities within a single, large research institute- the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIAID-NIH) in Bethesda, Maryland, U.S. Ten distinct murine norovirus strains were isolated from various tissues and feces of asymptomatic wild type sentinel mice as well as asymptomatic immunodeficient (RAG 2−/−) mice. The NIH MNV isolates showed little cytopathic effect in permissive RAW264.7 cells in early passages, but all isolates examined could be adapted to efficient growth in cell culture by serial passage. The viruses, although closely related in genome sequence, were distinguishable from each other according to facility location, likely due to the introduction of new viruses into each facility from separate sources or vendors at different times. Our study indicates that the murine noroviruses are widespread in these animal facilities, despite rigorous guidelines for animal care and maintenance

Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover

Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL