Gamma Ray Line Constraints on Effective Theories of Dark Matter

A monochromatic gamma ray line results when dark matter particles in the galactic halo annihilate to produce a two body final state which includes a photon. Such a signal is very distinctive from astrophysical backgrounds, and thus represents an incisive probe of theories of dark matter. We compare the recent null results of searches for gamma ray lines in the galactic center and other regions of the sky with the predictions of effective theories describing the interactions of dark matter particles with the Standard Model. We find that the null results of these searches provide constraints on the nature of dark matter interactions with ordinary matter which are complementary to constraints from other observables, and stronger than collider constraints in some cases.Comment: 20 pages, 9 figure

Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis

Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A. A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus (EBV) was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with Single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for EBV serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI). Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045), and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years vs 6.6 years before the clinical onset of multiple sclerosis). In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases

REBALANCING DISRUPTIVE BUSINESS OF MULTINATIONAL CORPORATIONS AND GLOBAL VALUE CHAINS WITHIN DEMOCRATIC AND INCLUSIVE CITIZENSHIP PROCESSES- REVIEW WORKING PAPER

The purpose of this working paper is to conduct a comprehensive review of existing literature that explores the relationship between business organizations and democracy. This review draws from various fields, including management, business ethics, sociology, international law, and other relevant disciplines for this Project and has several objectives. Firstly, it aims to provide insight into prior research on how democratic institutions regulate economic actors and how these actors, particularly large multinational corporations (MNCs), resist such regulation. Additionally, it examines how these economic actors develop behaviors and economic models that pose challenges to democratic governance, such as business-related human rights violations. In the initial part of the review, we delve into the historical and contemporary aspects of the relationship between business and democracy. Furthermore, the report explores how companies can contribute to shaping a more democratic future by addressing gaps in governance, especially in cases where populist governments fail to protect the rights of their citizens. It also considers the development of alternative business models, such as social enterprises and cross-sector partnerships. Moreover, it looks into how businesses can actively engage in democratic governance and promote principles of participation. The final section of the working paper involves a bibliometric analysis, including co authorship, co-citation, and keyword co-occurrence maps. This analysis is based on key references used by team members in their literature reviews and is designed to examine the connections that exist among various strands of research that support the research questions of the Rebalance Project

Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease that is refractory to medical intervention. Notch pathway antagonism has been shown to prevent pancreatic preneoplasia progression in mouse models, but potential benefits in the setting of an established PDA tumor have not been established. We demonstrate that the gamma secretase inhibitor MRK003 effectively inhibits intratumoral Notch signaling in the KPC mouse model of advanced PDA. Although MRK003 monotherapy fails to extend the lifespan of KPC mice, the combination of MRK003 with the chemotherapeutic gemcitabine prolongs survival. Combination treatment kills tumor endothelial cells and synergistically promotes widespread hypoxic necrosis. These results indicate that the paucivascular nature of PDA can be exploited as a therapeutic vulnerability, and the dual targeting of the tumor endothelium and neoplastic cells by gamma secretase inhibition constitutes a rationale for clinical translation

The Mating-Type Chromosome in the Filamentous Ascomycete Neurospora tetrasperma Represents a Model for Early Evolution of Sex Chromosomes

We combined gene divergence data, classical genetics, and phylogenetics to study the evolution of the mating-type chromosome in the filamentous ascomycete Neurospora tetrasperma. In this species, a large non-recombining region of the mating-type chromosome is associated with a unique fungal life cycle where self-fertility is enforced by maintenance of a constant state of heterokaryosis. Sequence divergence between alleles of 35 genes from the two single mating-type component strains (i.e. the homokaryotic mat A or mat a-strains), derived from one N. tetrasperma heterokaryon (mat A+mat a), was analyzed. By this approach we were able to identify the boundaries and size of the non-recombining region, and reveal insight into the history of recombination cessation. The non-recombining region covers almost 7 Mbp, over 75% of the chromosome, and we hypothesize that the evolution of the mating-type chromosome in this lineage involved two successive events. The first event was contemporaneous with the split of N. tetrasperma from a common ancestor with its outcrossing relative N. crassa and suppressed recombination over at least 6.6 Mbp, and the second was confined to a smaller region in which recombination ceased more recently. In spite of the early origin of the first “evolutionary stratum”, genealogies of five genes from strains belonging to an additional N. tetrasperma lineage indicate independent initiations of suppressed recombination in different phylogenetic lineages. This study highlights the shared features between the sex chromosomes found in the animal and plant kingdoms and the fungal mating-type chromosome, despite fungi having no separate sexes. As is often found in sex chromosomes of plants and animals, recombination suppression of the mating-type chromosome of N. tetrasperma involved more than one evolutionary event, covers the majority of the mating-type chromosome and is flanked by distal regions with obligate crossovers

Demographic routes to variability and regulation in bird populations

There is large interspecific variation in the magnitude of population fluctuations, even among closely related species. The factors generating this variation are not well understood, primarily because of the challenges of separating the relative impact of variation in population size from fluctuations in the environment. Here, we show using demographic data from 13 bird populations that magnitudes of fluctuations in population size are mainly driven by stochastic fluctuations in the environment. Regulation towards an equilibrium population size occurs through density-dependent mortality. At small population sizes, population dynamics are primarily driven by environment-driven variation in recruitment, whereas close to the carrying capacity K, variation in population growth is more strongly influenced by density-dependent mortality of both juveniles and adults. Our results provide evidence for the hypothesis proposed by Lack that population fluctuations in birds arise from temporal variation in the difference between density-independent recruitment and density-dependent mortality during the non-breeding season.Peer reviewe

Genetic variance in fitness indicates rapid contemporary adaptive evolution in wild animals

Funding: Hoge Veluwe great tits: the NIOO-KNAW, ERC, and numerous funding agencies; Wytham great tits: Biotechnology and Biological Sciences Research Council, ERC, and the UK Natural Environment Research Council (NERC).The rate of adaptive evolution, the contribution of selection to genetic changes that increase mean fitness, is determined by the additive genetic variance in individual relative fitness. To date, there are few robust estimates of this parameter for natural populations, and it is therefore unclear whether adaptive evolution can play a meaningful role in short-term population dynamics. We developed and applied quantitative genetic methods to long-term datasets from 19 wild bird and mammal populations and found that, while estimates vary between populations, additive genetic variance in relative fitness is often substantial and, on average, twice that of previous estimates. We show that these rates of contemporary adaptive evolution can affect population dynamics and hence that natural selection has the potential to partly mitigate effects of current environmental change.PostprintPeer reviewe

Flame retardants, surfactants and organotins in sediment and mysid shrimp of the Scheldt estuary (The Netherlands)

Author Posting. © The Authors, 2004. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Environmental Pollution 136 (2005): 19-31, doi:10.1016/j.envpol.2004.12.008.Sediment and mysids from the Scheldt estuary, one of the largest and most polluted estuaries in Western Europe, were analyzed for a number of contaminants that have shown to possess endocrine-disrupting activity, i.e. organotins, polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), tetrabromobisphenol A (TBBPA), nonylphenol ethoxylates (NPE) and transformation products nonylphenol (NP) and nonylphenol ether carboxylates (NPEC). In addition, in vitro estrogenic and androgenic potencies of water and sediment extracts were determined. Total organotin concentrations ranged from 84 to 348 ng/g dw in sediment and 1110 to 1370 ng/g dw in mysid. Total PBDE (excluding BDE-209) concentrations ranged from 14 to 22 ng/g dw in sediment and from 1765 to 2962 ng/g lipid in mysid. High concentrations of BDE-209 (240-1650 ng/g dw) were detected in sediment and mysid (269-600 ng/g lipid). Total HBCD concentrations in sediment and mysid were 14-71 ng/g dw and 562-727 ng/g lipid, respectively. Total NPE concentrations in sediment were 1422 ng/g dw, 1222 ng/g dw for NP and 80 ng/g dw for NPEC and ranged from 430 to 1119 ng/g dw for total NPE and from 206 to 435 ng/g dw for NP in mysid. Significant estrogenic potency, as analyzed using the yeast estrogen assay, was detected in sediment and water samples from the Scheldt estuary, but no androgenic activity was found. This study is the first to report high levels of endocrine disruptors in estuarine mysids.Funding to Tim Verslycke was provided by a research grant of the Flemish Institute for the Promotion of Scientific and Technological Research in Industry (IWT-V, Belgium) and a postdoctoral award by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the Ocean Life Institute. The chemical analysis was financially supported by the National Institute for Coastal and Marine Management (RIKZ, The Netherlands)

Archiving primary data: solutions for long-term studies

The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers

Biological interpretation of genome-wide association studies using predicted gene functions

Jaakko Kaprio on Genetic Invest ANthropometric Trai -työryhmän jäsen.The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes.Peer reviewe