Metastable GeV-scale particles as a solution to the cosmological lithium problem

The persistent discrepancy between observations of 7Li with putative primordial origin and its abundance prediction in Big Bang Nucleosynthesis (BBN) has become a challenge for the standard cosmological and astrophysical picture. We point out that the decay of GeV-scale metastable particles X may significantly reduce the BBN value down to a level at which it is reconciled with observations. The most efficient reduction occurs when the decay happens to charged pions and kaons, followed by their charge exchange reactions with protons. Similarly, if X decays to muons, secondary electron antineutrinos produce a similar effect. We consider the viability of these mechanisms in different classes of new GeV-scale sectors, and find that several minimal extensions of the Standard Model with metastable vector and/or scalar particles are capable of solving the cosmological lithium problem. Such light states can be a key to the explanation of recent cosmic ray anomalies and can be searched for in a variety of high-intensity medium-energy experiments.Comment: 50 pages, 13 figures; references added, typo correcte

The Molecular Vista: Current Perspectives on Molecules and Life in the Twentieth Century

This essay considers how scholarly approaches to the development of molecular biology have too often narrowed the historical aperture to genes, overlooking the ways in which other objects and processes contributed to the molecularization of life. From structural and dynamic studies of biomolecules to cellular membranes and organelles to metabolism and nutrition, new work by historians, philosophers, and STS scholars of the life sciences has revitalized older issues, such as the relationship of life to matter, or of physicochemical inquiries to biology. This scholarship points to a novel molecular vista that opens up a pluralist view of molecularizations in the twentieth century and considers their relevance to current science

Exploring concurrency and reachability in the presence of high temporal resolution

Network properties govern the rate and extent of spreading processes on networks, from simple contagions to complex cascades. Recent advances have extended the study of spreading processes from static networks to temporal networks, where nodes and links appear and disappear. We review previous studies on the effects of temporal connectivity for understanding the spreading rate and outbreak size of model infection processes. We focus on the effects of "accessibility", whether there is a temporally consistent path from one node to another, and "reachability", the density of the corresponding "accessibility graph" representation of the temporal network. We study reachability in terms of the overall level of temporal concurrency between edges, quantifying the overlap of edges in time. We explore the role of temporal resolution of contacts by calculating reachability with the full temporal information as well as with a simplified interval representation approximation that demands less computation. We demonstrate the extent to which the computed reachability changes due to this simplified interval representation.Comment: To appear in Holme and Saramaki (Editors). "Temporal Network Theory". Springer- Nature, New York. 201

Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity

Aims/hypothesis. Obese people exhibit reduced circulating peptide YY (PYY) levels, but it is unclear whether this is a consequence or cause of obesity. We therefore investigated the effect of Pyy ablation on energy homeostasis. Methods. Body composition, i.p. glucose tolerance, food intake and hypothalamic neuropeptide expression were determined in Pyy knock-out and wild-type mice on a normal or high-fat diet. Results. Pyy knock-out significantly increased bodyweight and increased fat mass by 50% in aged females on a normal diet. Male chow-fed Pyy −/− mice were resistant to obesity but became significantly fatter and glucose-intolerant compared with wild-types when fed a high-fat diet. Pyy knock-out animals exhibited significantly elevated fasting or glucose-stimulated serum insulin concentrations vs wild-types, with no increase in basal or fasting-induced food intake. Pyy knock-out decreased or had no effect on neuropeptide Y expression in the arcuate nucleus of the hypothalamus, and significantly increased proopiomelanocortin expression in this region. Male but not female knock-outs exhibited significantly increased growth hormone-releasing hormone expression in the ventromedial hypothalamus and significantly elevated serum IGF-I and testosterone levels. This sex difference in activation of the hypothalamo–pituitary somatotrophic axis by Pyy ablation may contribute to the resistance of chow-fed male knock-outs to late-onset obesity. Conclusions/interpretation. PYY signalling is important in the regulation of energy balance and glucose homeostasis, possibly via regulation of insulin release. Therefore reduced PYY levels may predispose to the development of obesity, particularly with ageing or under conditions of high-fat feeding

Human immunodeficiency virus: 25 years of diagnostic and therapeutic strategies and their impact on hepatitis B and C virus

The human immunodeficiency virus (HIV) had spread unrecognized in the human population as sexually transmitted disease and was finally identified by its disease AIDS in 1981. Even after the isolation of the causative agent in 1983, the burden and death rate of AIDS accelerated worldwide especially in young people despite the confection of new drugs capable to inhibit virus replication since 1997. However, at least in industrialised countries, this trend could be reversed by the introduction of combination therapy strategies. The design of new drugs is on going; besides the inhibition of the three enzymes of HIV for replication and maturation (reverse transcriptase, integrase and protease), further drugs inhibits fusion of viral and cellular membranes and virus maturation. On the other hand, viral diagnostics had been considerably improved since the emergence of HIV. There was a need to identify infected people correctly, to follow up the course of immune reconstitution of patients by measuring viral load and CD4 cells, and to analyse drug escape mutations leading to drug resistance. Both the development of drugs and the refined diagnostics have been transferred to the treatment of patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). This progress is not completed; there are beneficial aspects in the response of the scientific community to the HIV burden for the management of other viral diseases. These aspects are described in this contribution. Further aspects as handling a stigmatising disease, education of self-responsiveness within sexual relationships, and ways for confection of a protective vaccine are not covered

Bioinformatic and statistical analysis of the optic nerve head in a primate model of ocular hypertension

<p>Abstract</p> <p>Background</p> <p>The nonhuman primate model of glaucomatous optic neuropathy most faithfully reproduces the human disease. We used high-density oligonucleotide arrays to investigate whole genome transcriptional changes occurring at the optic nerve head during primate experimental glaucoma.</p> <p>Results</p> <p>Laser scarification of the trabecular meshwork of cynomolgus macaques produced elevated intraocular pressure that was monitored over time and led to varying degrees of damage in different samples. The macaques were examined clinically before enucleation and the myelinated optic nerves were processed post-mortem to determine the degree of neuronal loss. Global gene expression was examined in dissected optic nerve heads with Affymetrix GeneChip microarrays. We validated a subset of differentially expressed genes using qRT-PCR, immunohistochemistry, and immuno-enriched astrocytes from healthy and glaucomatous human donors. These genes have previously defined roles in axonal outgrowth, immune response, cell motility, neuroprotection, and extracellular matrix remodeling.</p> <p>Conclusion</p> <p>Our findings show that glaucoma is associated with increased expression of genes that mediate axonal outgrowth, immune response, cell motility, neuroprotection, and ECM remodeling. These studies also reveal that, as glaucoma progresses, retinal ganglion cell axons may make a regenerative attempt to restore lost nerve cell contact.</p