TOPOLOGICAL DEFECTS AND HIGHEST ENERGY COSMIC AND GAMMA RAYS

In this paper we review the hypothesis that a considerable part of the cosmic ray flux observed above about 10^{19}\eV may be produced by decaying or annihilating topological defects left over from phase transitions in the early universe at grand unification energy scales (\approx10^{16}\GeV). Possible signatures of cosmic ray producing defect models are discussed which could be tested experimentally in the near future. We thereby focus on model independent universal spectral properties of the predicted particle fluxes.Comment: 11 pages of uuencoded compressed postscript, including 3 figures, to be published in Space Science Reviews

The Cosmic Microwave Background and Particle Physics

In forthcoming years, connections between cosmology and particle physics will be made increasingly important with the advent of a new generation of cosmic microwave background (CMB) experiments. Here, we review a number of these links. Our primary focus is on new CMB tests of inflation. We explain how the inflationary predictions for the geometry of the Universe and primordial density perturbations will be tested by CMB temperature fluctuations, and how the gravitational waves predicted by inflation can be pursued with the CMB polarization. The CMB signatures of topological defects and primordial magnetic fields from cosmological phase transitions are also discussed. Furthermore, we review current and future CMB constraints on various types of dark matter (e.g. massive neutrinos, weakly interacting massive particles, axions, vacuum energy), decaying particles, the baryon asymmetry of the Universe, ultra-high-energy cosmic rays, exotic cosmological topologies, and other new physics.Comment: 43 pages. To appear in Annual Reviews of Nuclear and Particle Scienc

Angiogenin protects motoneurons against hypoxic injury.

Cells can adapt to hypoxia through the activation of hypoxia-inducible factor-1 (HIF-1), which in turn regulates the expression of hypoxia-responsive genes. Defects in hypoxic signaling have been suggested to underlie the degeneration of motoneurons in amyotrophic lateral sclerosis (ALS). We have recently identified mutations in the hypoxia-responsive gene, angiogenin (ANG), in ALS patients, and have shown that ANG is constitutively expressed in motoneurons. Here, we show that HIF-1alpha is sufficient and required to activate ANG in cultured motoneurons exposed to hypoxia, although ANG expression does not change in a transgenic ALS mouse model or in sporadic ALS patients. Administration of recombinant ANG or expression of wild-type ANG protected motoneurons against hypoxic injury, whereas gene silencing of ang1 significantly increased hypoxia-induced cell death. The previously reported ALS-associated ANG mutations (Q12L, K17I, R31K, C39W, K40I, I46V) all showed a reduced neuroprotective activity against hypoxic injury. Our data show that ANG plays an important role in endogenous protective pathways of motoneurons exposed to hypoxia, and suggest that loss of function rather than loss of expression of ANG is associated with ALS

Identification of Novel Single Nucleotide Polymorphisms (SNPs) in Deer (Odocoileus spp.) Using the BovineSNP50 BeadChip

Single nucleotide polymorphisms (SNPs) are growing in popularity as a genetic marker for investigating evolutionary processes. A panel of SNPs is often developed by comparing large quantities of DNA sequence data across multiple individuals to identify polymorphic sites. For non-model species, this is particularly difficult, as performing the necessary large-scale genomic sequencing often exceeds the resources available for the project. In this study, we trial the Bovine SNP50 BeadChip developed in cattle (Bos taurus) for identifying polymorphic SNPs in cervids Odocoileus hemionus (mule deer and black-tailed deer) and O. virginianus (white-tailed deer) in the Pacific Northwest. We found that 38.7% of loci could be genotyped, of which 5% (n = 1068) were polymorphic. Of these 1068 polymorphic SNPs, a mixture of putatively neutral loci (n = 878) and loci under selection (n = 190) were identified with the FST-outlier method. A range of population genetic analyses were implemented using these SNPs and a panel of 10 microsatellite loci. The three types of deer could readily be distinguished with both the SNP and microsatellite datasets. This study demonstrates that commercially developed SNP chips are a viable means of SNP discovery for non-model organisms, even when used between very distantly related species (the Bovidae and Cervidae families diverged some 25.1−30.1 million years before present)

Protocol for a realist synthesis of health systems responsiveness in low-income and middle-income countries

Introduction Health systems responsiveness is a key objective of any health system, yet it is the least studied of all objectives particularly in low-income and middle-income countries. Research on health systems responsiveness highlights its multiple elements, for example, dignity and confidentiality. Little is known, however, about underlying theories of health systems responsiveness, and the mechanisms through which responsiveness works. This realist synthesis contributes to bridging these two knowledge gaps. Methods and analysis In this realist synthesis, we will use a four-step process, comprising: mapping of theoretical bases, formulation of programme theories, theory refinement and testing of programme theories using literature and empirical data from Ghana and Vietnam. We will include theoretical and conceptual pieces, reviews, empirical studies and grey literature, alongside the primary data. We will explore responsiveness as entailing external and internal interactions within health systems. The search strategy will be purposive and iterative, with continuous screening and refinement of theories. Data extraction will be combined with quality appraisal, using appropriate tools. Each fragment of evidence will be appraised as it is being extracted, for its relevance to the emerging programme theories and methodological rigour. The extracted data pertaining to contexts, mechanisms and outcomes will be synthesised to identify patterns and contradictions. Results will be reported using narrative explanations, following established guidance on realist syntheses. Ethics and dissemination Ethics approvals for the wider RESPONSE (Improving health systems responsiveness to neglected health needs of vulnerable groups in Ghana and Vietnam) study, of which this review is one part, were obtained from the ethics committees of the following institutions: London School of Hygiene and Tropical Medicine (ref: 22981), University of Leeds, School of Medicine (ref: MREC19-051), Ghana Health Service (ref: GHS-ERC 012/03/20) and Hanoi University of Public Health (ref: 020-149/DD-YTCC). We will disseminate results through academic papers, conference presentations and stakeholder workshops in Ghana and Vietnam. PROSPERO registration number CRD42020200353. Full record: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020200353

The importance of service quality in British Muslim’s choice of an Islamic or non-Islamic bank account

Using an extended SERVQUAL model, this study identifies and compares the importance of service quality to Muslim consumers with an Islamic or non-Islamic bank account in a non-Muslim country, Britain. Eight group discussions and survey with 300 Muslims were conducted. Five dimensions of service quality were identified, i.e. Responsiveness, Credibility, Islamic Tangibles, Accessibility and Reputation. These differ in structure and content from the original SERVQUAL developed in the west and the subsequent CARTER model constructed in a Muslim country. In addition, significant differences were found in the importance rating of items by respondents holding an account with an Islamic bank compared to those with a non-Islamic bank account. This study is one of the first to identify and compare the importance of service quality between Islamic and non-Islamic bank account holders in a western non-Muslim country. The results advance our understanding of the impact of culture on SERVQUAL. The study provides insight into Muslims’ bank choice and helps bank managers of both Islamic and non-Islamic banks to focus their attention on the service quality dimensions that matter most to Muslim customers

Absence of Ataxin-3 Leads to Enhanced Stress Response in C. elegans

Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein degradation by the ubiquitin-proteasome pathway. C. elegans and mouse ataxin-3 knockout models are viable and without any obvious phenotype in a basal condition however their phenotype in stress situations has never been described

Mechanisms of local immunosuppression in cutaneous melanoma

Cutaneous melanoma is highly immunogenic, yet primary melanomas and metastases develop successfully in otherwise immunocompetent patients. To investigate the local immunosuppressive microenvironment, we examined the presence of suppressor T lymphocytes and tolerising dendritic cells (DCs), the expression of immunosuppressive cytokines (IL-10, TGFβ1 and TGFβ2) and the enzyme indoleamine 2,3-dioxygenase (IDO) using qRT–PCR and immunohistochemistry in primary skin melanomas, negative and positive sentinel lymph nodes (SLN), and lymph nodes with advanced metastases. Our results indicate that tolerogenic DCs and suppressor T lymphocytes are present in melanoma at all stages of disease progression. They express transforming growth factor β receptor 1 (TGFβR1), and are therefore susceptible to TGFβ1 and TGFβ2 specifically expressed by primary melanoma. We found that expression of IDO and interleukin 10 (IL-10) increased with melanoma progression, with the highest concentration in positive SLN. We suggest that negative SLN contain immunosuppressive cells and cytokines, due to preconditioning by tolerogenic DCs migrating from the primary melanoma site to the SLN. In primary melanoma, TGFβ2 is likely to render peripheral DCs tolerogenic, while in lymph nodes IDO and TGFβ1 may have a major effect. This mechanism of tumour-associated immunosuppression may inhibit the immune response to the tumour and may explain the discrepancy between the induction of systemic immunity by anti-melanoma vaccines and their poor performance in the clinic

To Each According to His Need? Variability in the Responses to Inequity in Nonhuman Primates

While it is well established that humans respond to inequity, it remains unclear the extent to which this behavior occurs in our nonhuman primate relatives. By comparing a variety of species, spanning from New World and Old World monkeys to great apes, scientists can begin to answer questions about how the response to inequity evolved, what the function of this response is, and why and how different contexts shape it. In particular, research across nonhuman primate species suggests that the response is quite variable across species, contexts and individuals. In this paper, we aim to review these differences in an attempt to identify and better understand the patterns that emerge from the existing data with the goal of developing directions for future research. To begin, we address the importance of considering socio-ecological factors in nonhuman primates in order to better understand and predict expected patterns of cooperation and aversion to inequity in different species, following which we provide a detailed analysis of the patterns uncovered by these comparisons. Ultimately, we use this synthesis to propose new ideas for research to better understand this response and, hence, the evolution of our own responses to inequity

Environmental barriers to sociality in an obligate eusocial sweat bee

This is the final version of the article. Available from Springer Verlag via the DOI in this record.All data generated or analysed during this study are included in this published article and its supplementary materials.Understanding the ecological and environmental contexts in which eusociality can evolve is fundamental to elucidating its evolutionary origins. A sufficiently long active season is postulated to have been a key factor facilitating the transition to eusociality. Many primitively eusocial species exhibit an annual life cycle, which is thought to preclude the expression of eusociality where the active season is too short to produce successive worker and reproductive broods. However, few studies have attempted to test this idea experimentally. We investigated environmental constraints on the expression of eusociality in the obligate primitively eusocial sweat bee Lasioglossum malachurum, by transplanting nest foundresses from the south to the far north of the United Kingdom, far beyond the natural range of L. malachurum. We show that transplanted bees can exhibit eusociality, but that the short length of the season and harsher environmental conditions could preclude its successful expression. In one year, when foundresses were transplanted only after provisioning first brood (B1) offspring, workers emerged in the north and provisioned a second brood (B2) of reproductives. In another year, when foundresses were transplanted prior to B1 being provisioned, they were just as likely to initiate nesting and provisioned just as many B1 cells as foundresses in the south. However, the life cycle was delayed by approximately 7 weeks and nests suffered 100% B1 mortality. Our results suggest that short season length together with poor weather conditions represent an environmental barrier to the evolution and expression of eusociality in sweat bees.This work formed part of a studentship (1119965) awarded to PJD funded by the Natural Environment Research Council and the University of Sussex, supervised by JF