Gamma-ray line emission from Al-26 produced by Wolf-Rayet stars

The recent satellite observations of the 1.8 MeV line from the decay of Al-26 has given a new impetus to the study of the nucleosynthesis of Al-26. The production and ejection of Al-26 by massive mass-losing stars (Of and WR stars) is discussed in the light of recent stellar models. The longitude distribution of the Al-26 gamma ray line emission produced by the galactic collection of WR stars is derived based on various estimates of their radial distribution. This longitude profile provides: (1) a specific signature of massive stars on the background of other potential Al-26 sources, as novae, supernovae, certain red giants and possibly AGB stars; and (2) a possible tool to improve the data analysis of the HEAO 3 and SMM experiments

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

Interplay between TERT promoter mutations and methylation culminates in chromatin accessibility and TERT expression

The telomerase reverse transcriptase (TERT) gene is responsible for telomere maintenance in germline and stem cells, and is re-expressed in 90% of human cancers. CpG methylation in the TERT promoter (TERTp) was correlated with TERT mRNA expression. Furthermore, two hotspot mutations in TERTp, dubbed C228T and C250T, have been revealed to facilitate binding of transcription factor ETS/TCF and subsequent TERT expression. This study aimed to elucidate the combined contribution of epigenetic (promoter methylation and chromatin accessibility) and genetic (promoter mutations) mechanisms in regulating TERT gene expression in healthy skin samples and in melanoma cell lines (n = 61). We unexpectedly observed that the methylation of TERTp was as high in a subset of healthy skin cells, mainly keratinocytes, as in cutaneous melanoma cell lines. In spite of the high promoter methylation fraction in wild-type (WT) samples, TERT mRNA was only expressed in the melanoma cell lines with either high methylation or intermediate methylation in combination with TERT mutations. TERTp methylation was positively correlated with chromatin accessibility and TERT mRNA expression in 8 melanoma cell lines. Cooperation between epigenetic and genetic mechanisms were best observed in heterozygous mutant cell lines as chromosome accessibility preferentially concerned the mutant allele. Combined, these results suggest a complex model in which TERT expression requires either a widely open chromatin state in TERTp-WT samples due to high methylation throughout the promoter or a combination of moderate methylation fraction/chromatin accessibility in the presence of the C228T or C250T mutations.Dermatology-oncolog

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

Molecular techniques for pathogen identification and fungus detection in the environment

Many species of fungi can cause disease in plants, animals and humans. Accurate and robust detection and quantification of fungi is essential for diagnosis, modeling and surveillance. Also direct detection of fungi enables a deeper understanding of natural microbial communities, particularly as a great many fungi are difficult or impossible to cultivate. In the last decade, effective amplification platforms, probe development and various quantitative PCR technologies have revolutionized research on fungal detection and identification. Examples of the latest technology in fungal detection and differentiation are discussed here

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

Cytomegalovirus infection in pediatric rheumatic diseases: a review

Human cytomegalovirus (HCMV) is familiar to pediatric rheumatologists mainly as a cause of opportunistic disease in pharmacologically immune suppressed patients. However, HCMV also has a variety of immuno-modulatory effects, through which it may influence the course of rheumatic conditions. In this article we discuss the interplay between HCMV and the immune system, and review the clinical manifestations, diagnosis, and treatment of HCMV infection in children with rheumatic disease

Norovirus Regulation of the Innate Immune Response and Apoptosis Occurs via the Product of the Alternative Open Reading Frame 4

Small RNA viruses have evolved many mechanisms to increase the capacity of their short genomes. Here we describe the identification and characterization of a novel open reading frame (ORF4) encoded by the murine norovirus (MNV) subgenomic RNA, in an alternative reading frame overlapping the VP1 coding region. ORF4 is translated during virus infection and the resultant protein localizes predominantly to the mitochondria. Using reverse genetics we demonstrated that expression of ORF4 is not required for virus replication in tissue culture but its loss results in a fitness cost since viruses lacking the ability to express ORF4 restore expression upon repeated passage in tissue culture. Functional analysis indicated that the protein produced from ORF4 antagonizes the innate immune response to infection by delaying the upregulation of a number of cellular genes activated by the innate pathway, including IFN-Beta. Apoptosis in the RAW264.7 macrophage cell line was also increased during virus infection in the absence of ORF4 expression. In vivo analysis of the WT and mutant virus lacking the ability to express ORF4 demonstrated an important role for ORF4 expression in infection and virulence. STAT1-/- mice infected with a virus lacking the ability to express ORF4 showed a delay in the onset of clinical signs when compared to mice infected with WT virus. Quantitative PCR and histopathological analysis of samples from these infected mice demonstrated that infection with a virus not expressing ORF4 results in a delayed infection in this system. In light of these findings we propose the name virulence factor 1, VF1 for this protein. The identification of VF1 represents the first characterization of an alternative open reading frame protein for the calicivirus family. The immune regulatory function of the MNV VF1 protein provide important perspectives for future research into norovirus biology and pathogenesis