The Etiology of Multiple Sclerosis: Genetic Evidence for the Involvement of the Human Endogenous Retrovirus HERV-Fc1

We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact or almost-intact genes. We found that SNPs in the gene TRIM5 were inversely correlated with disease. Conversely, SNPs around one retroviral locus, HERV-Fc1, showed a highly significant association with disease. The latter association was limited to a narrow region that contains no other known genes. We conclude that HERV-Fc1 and TRIM5 play a role in the etiology of multiple sclerosis. If these results are confirmed, they point to new modes of treatment for multiple sclerosis

Can Preening Contribute to Influenza A Virus Infection in Wild Waterbirds?

Wild aquatic birds in the Orders Anseriformes and Charadriiformes are the main reservoir hosts perpetuating the genetic pool of all influenza A viruses, including pandemic viruses. High viral loads in feces of infected birds permit a fecal-oral route of transmission. Numerous studies have reported the isolation of avian influenza viruses (AIVs) from surface water at aquatic bird habitats. These isolations indicate aquatic environments have an important role in the transmission of AIV among wild aquatic birds. However, the progressive dilution of infectious feces in water could decrease the likelihood of virus/host interactions. To evaluate whether alternate mechanisms facilitate AIV transmission in aquatic bird populations, we investigated whether the preen oil gland secretions by which all aquatic birds make their feathers waterproof could support a natural mechanism that concentrates AIVs from water onto birds' bodies, thus, representing a possible source of infection by preening activity. We consistently detected both viral RNA and infectious AIVs on swabs of preened feathers of 345 wild mallards by using reverse transcription–polymerase chain reaction (RT-PCR) and virus-isolation (VI) assays. Additionally, in two laboratory experiments using a quantitative real-time (qR) RT-PCR assay, we demonstrated that feather samples (n = 5) and cotton swabs (n = 24) experimentally impregnated with preen oil, when soaked in AIV-contaminated waters, attracted and concentrated AIVs on their surfaces. The data presented herein provide information that expands our understanding of AIV ecology in the wild bird reservoir system

The Fecal Viral Flora of Wild Rodents

The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat) collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in mammals

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

What can whiskers tell us about mammalian evolution, behaviour, and ecology?

Most mammals have whiskers; however, nearly everything we know about whiskers derives from just a handful of species, including laboratory rats Rattus norvegicus and mice Mus musculus, as well as some species of pinniped and marsupial. We explore the extent to which the knowledge of the whisker system from a handful of species applies to mammals generally. This will help us understand whisker evolution and function, in order to gain more insights into mammalian behaviour and ecology. This review is structured around Tinbergen’s four questions, since this method is an established, comprehensive, and logical approach to studying behaviour. We ask: how do whiskers work, develop, and evolve? And what are they for? While whiskers are all slender, curved, tapered, keratinised hairs that transmit vibrotactile information, we show that there are marked differences between species with respect to whisker arrangement, numbers, length, musculature, development, and growth cycles. The conservation of form and a common muscle architecture in mammals suggests that early mammals had whiskers. Whiskers may have been functional even in therapsids. However, certain extant mammalian species are equipped with especially long and sensitive whiskers, in particular nocturnal, arboreal species, and aquatic species, which live in complex environments and hunt moving prey. Knowledge of whiskers and whisker use can guide us in developing conservation protocols and designing enriched enclosures for captive mammals. We suggest that further comparative studies, embracing a wider variety of mammalian species, are required before one can make large-scale predictions relating to evolution and function of whiskers. More research is needed to develop robust techniques to enhance the welfare and conservation of mammals

The performance of a laboratory facility for evaluating the structural response of small-diameter buried pipes

The performance of a new laboratory facility for testing small-diameter buried pipes (less than 300 mm diameter) subject to the biaxially compressive earth pressures expected to prevail under deep and extensive overburden is examined. The new facility consists of a prism of soil 2.0 m wide × 2.0 m long × 1.6 m high contained within a stiff steel structure. Laboratory tests were performed in the new test facility to examine the appropriateness of the boundary conditions imposed during testing. Overburden pressures are successfully simulated with a pressurized air bladder. Boundary friction was limited to only minimal effects with lubricated polyethylene sheets. The stiffness of the lateral boundary is sufficiently large to induce lateral stresses close to those for zero lateral strain conditions. Overall, the effects on the pipe arising from the idealizations involved in the laboratory model were found to be small. The application of the new test cell is illustrated by using it to assess the response of a small-diameter landfill leachate collection pipe under two different backfill conditions. This comparison showed that the structural response of the pipe is significantly impacted by the coarse gravel backfill used in landfill drainage layers. Maximum pipe deflections and strains were nearly twice as large when tested in the coarse gravel compared with the sand backfill. Much greater variations of deflection and strain were also measured with the coarse gravel when compared with the sand backfill due to local bending effects from the coarse gravel.Key words: buried pipes, soil-structure interaction, laboratory testing, leachate collection pipes. </jats:p

The design of a laboratory facility for evaluating the structural response of small-diameter buried pipes

The design of a new laboratory facility for evaluating the structural response of small-diameter buried pipes (e.g., leachate collection pipes in landfills) is presented. The pipe is tested within a 2.0 m wide, 2.0 m long, and 1.6 m high prism of soil, subject to large vertical pressures (1000 kPa), with only minimal roughness and deflection of the lateral boundaries. Results from finite element analyses are presented to examine the effect of proximity, roughness, and stiffness of the lateral boundary on the soil and pipe response and how reasonable the laboratory idealizations are relative to the deep burial conditions expected to prevail in the field. Shear stresses arising from the roughness of the lateral boundaries alter the stresses acting around the pipe and reduce the proportion of the applied surcharge reaching the pipe. Outward deflection of the lateral boundaries also alters the stress state around the pipe, predominantly resulting from decreases in horizontal stresses within the soil. Reducing boundary friction to less than 5° and limiting the boundary deformation to less than 1 mm at a vertical surcharge of 1000 kPa provide a good idealization of field conditions for a deeply buried pipe.Key words: buried pipes, soil-structure interaction, laboratory testing, boundary friction.</jats:p

Local strain on a leachate collection pipe

Local strain measurements opposite gravel contacts and around a single isolated perforation are reported for a high-density-polyethylene pipe (320 mm outside diameter, 32 mm thick) typical of that commonly used as part of the leachate collection system in municipal solid waste landfills. Emphasis is given to examining the localized effect of coarse gravel contacts on pipe strain and the strain distribution around the perforation. The laboratory testing featured a cylindrical volume of soil with the pipe located in the middle with radially compressive stresses applied along the outer perimeter of the backfill. Two different backfill materials were used. When tested with medium sand backfill the pipe response was essentially uniform, indicative of the near-continuous support and loading provided by the sand. Large variations in local pipe strains were measured with coarse gravel backfill, such as that used in landfill leachate collection systems. Local bending induced by the discontinuous support and loading from the coarse gravel resulted in variations in circumferential and axial strains of over 40%. The local bending effects were not sufficiently large to produce circumferential tension in the pipe tested. A multiplication factor of 1.5 is suggested to account for increases in compressive strain from the coarse gravel. Measurements of surface strain around an isolated 32 mm diameter perforation revealed that a complex three-dimensional response is induced by the presence of the hole. Maximum strains near the hole were found to be 2.7 times larger than those distant from the perforation.Key words: leachate collection pipes, HDPE pipes, leachate collection systems, landfill design. </jats:p