Effect of salt and temperature stresses on survival and infectivity of Heterorhabditis spp. IJs

Heterorhabditis is frequently found in coastal sandy soils where it may experience both high salinity and high temperatures. We tested the ability of infective juveniles (IJs) of three taxonomic groups of Heterorhabditis to infect insects in saline sand. We also tested whether salinity (sea water) affected the IJs' ability to tolerate elevated temperatures in aqueous suspension and in sand. IJs of all three taxonomic groups killed Galleria mellonella in saline sand (25.6% insects killed), but at a lower level than in non-saline sand (96.5% insects killed). Exposure of IJs in sand to high temperature reduced their ability to kill G. mellonella at 20 degrees C; heating IJs in saline sand reduced G. mellonella mortality to a lesser extent (25.6% at 20 degrees C, 18.3% at 39 degrees C) than heating in non-saline sand (96.5% at 20 degrees C, 17.5% at 39 degrees C). In aqueous suspension, IJs of the North-West European and Irish types of Heterorhabditis tolerated high temperature better in sea water (at least 95% survived 1 h at 39 C) than in distilled water (none survived 1 h at 38 degrees C). H. bacteriophora was more temperature tolerant: survival and subsequent infectivity of IJs was unaffected by temperature up to 39 degrees C in either medium. It was concluded that high salinity (sea water) reduces the ability of Heterorhabditis IJs to infect, but improves their tolerance of high temperature

Effect of salt and temperature stresses on survival and infectivity of Heterorhabditis spp. IJs

Heterorhabditis is frequently found in coastal sandy soils where it may experience both high salinity and high temperatures. We tested the ability of infective juveniles (IJs) of three taxonomic groups of Heterorhabditis to infect insects in saline sand. We also tested whether salinity (sea water) affected the IJs' ability to tolerate elevated temperatures in aqueous suspension and in sand. IJs of all three taxonomic groups killed Galleria mellonella in saline sand (25.6% insects killed), but at a lower level than in non-saline sand (96.5% insects killed). Exposure of IJs in sand to high temperature reduced their ability to kill G. mellonella at 20 degrees C; heating IJs in saline sand reduced G. mellonella mortality to a lesser extent (25.6% at 20 degrees C, 18.3% at 39 degrees C) than heating in non-saline sand (96.5% at 20 degrees C, 17.5% at 39 degrees C). In aqueous suspension, IJs of the North-West European and Irish types of Heterorhabditis tolerated high temperature better in sea water (at least 95% survived 1 h at 39 C) than in distilled water (none survived 1 h at 38 degrees C). H. bacteriophora was more temperature tolerant: survival and subsequent infectivity of IJs was unaffected by temperature up to 39 degrees C in either medium. It was concluded that high salinity (sea water) reduces the ability of Heterorhabditis IJs to infect, but improves their tolerance of high temperature

Mongoose Manor: Herpestidae remains from the Early Pleistocene Cooper’s D locality in the Cradle of Humankind, Gauteng, South Africa

Mongooses (Herpestidae) are an important component of African ecosystems, and a common constituent of southern African fossil assemblages. Despite this, mongoose fossils from the Cradle of Humankind, Gauteng, South Africa, have received relatively little interest. This paper presents the diverse mongoose craniodental assemblage from the early Pleistocene fossil locality Cooper’s D. A total of 29 mongoose specimens from five genera were identified at Cooper’s, including numerous first appearances in the Cradle or in South Africa. The exceptional mongoose assemblage at Cooper’s likely reflects the effects of an unknown taphonomic process, although mongooses follow other carnivore groups in the Cradle in displaying an apparent preference for the southern part of the Cradle. This investigation shows the value of mongooses as palaeoecological indicators and supports previous interpretations of the environment at Cooper’s as grassland with a strong woody component near a permanent water source.Palaeontological Scientific Trust (PAST); DST-NRF Centre of Excellence, Palaeosciences (CoE-Pal); the South African National Research Foundation; and the University of the Witwatersrand Postgraduate Merit Award.JNC201

Arctic in Rapid Transition (ART) : science plan

The Arctic is undergoing rapid transformations that have brought the Arctic Ocean to the top of international political agendas. Predicting future conditions of the Arctic Ocean system requires scientific knowledge of its present status as well as a process-based understanding of the mechanisms of change. The Arctic in Rapid Transition (ART) initiative is an integrative, international, interdisciplinary pan-Arctic program to study changes and feedbacks among the physical and biogeochemical components of the Arctic Ocean and their ultimate impacts on biological productivity. The goal of ART is to develop priorities for Arctic marine science over the next decade. Three overarching questions form the basis of the ART science plan: (1) How were past transitions in sea ice connected to energy flows, elemental cycling, biological diversity and productivity, and how do these compare to present and projected shifts? (2) How will biogeochemical cycling respond to transitions in terrestrial, gateway and shelf-to-basin fluxes? (3) How do Arctic Ocean organisms and ecosystems respond to environmental transitions including temperature, stratification, ice conditions, and pH? The integrated approach developed to answer the ART key scientific questions comprises: (a) process studies and observations to reveal mechanisms, (b) the establishment of links to existing monitoring programs, (c) the evaluation of geological records to extend time-series, and (d) the improvement of our modeling capabilities of climate-induced transitions. In order to develop an implementation plan for the ART initiative, an international and interdisciplinary workshop is currently planned to take place in Winnipeg, Canada in October 2010

Mustelid and viverrid remains from the Pleistocene site of Cooper’s D, Gauteng, South Africa

Fossil mustelids and viverrids are rare in the African Pleistocene fossil record. The careful examination of sieved sediments from the well-dated Cooper’s D locality in Gauteng has revealed six new mustelid and viverrid specimens. These represent three uncommon genera – two mustelids, Propoecilogale bolti and Mellivora capensis, and a viverrid, Civettictis cf. civetta. We describe and figure these six specimens here. Cooper’sD is only the fourth African locality at which P. bolti has been identified, and it is the first of the Witwatersrand sites to contain remains of the African civet.Palaeontological Scientific Trust NRF/DST Centre of Excellence in Palaeosciences South African National Research Foundation University of the Witwatersrand Postgraduate Merit Award Liverpool John Moores University Early Career Researcher Awar

The Arctic in Rapid Transition (ART) Initiative: integrating priorities for Arctic marine science over the next decade

The Arctic is currently undergoing rapid environmental and economic transformations. Recent and ongoing climate warming which is simplifying access to oil and gas resources, enabling trans-Arctic shipping and shifting the distribution of harvestable resources, has brought the Arctic Ocean to the top of national and international political agendas. Scientific knowledge of the present status of the Arctic Ocean and the process-based understanding needed to make predictions throughout the arctic region are thus urgently required. A step towards improving our capacity to predict future arctic change was undertaken with the Second International Conference on Arctic Research Planning (ICARP II) meetings in 2005 and 2006 which brought together scientists, policymakers, research managers, arctic residents and other stakeholders interested in the future of arctic climate change research. The Arctic in Rapid Transition (ART) Initiative developed out of an effort to synthesize the several resulting ICARP II science plans specific to the marine environment and has been a process driven by the early career scientists of the ICARP II Marine Roundtable. To this end, the ART Initiative is an integrative, international, multi-disciplinary, long-term pan-Arctic program to study changes and feedbacks among the physical characteristics and biogeochemical cycles of the Arctic Ocean and its' resulting capacity for biological productivity. The first ART workshop was held in Fairbanks, Alaska in November 2009 with 58 participants, the results of which will help to develop a science and implementation plan that integrates, updates and develops priorities for arctic marine science over the next decade. Our focus within the ART Initiative will be to bridge gaps in knowledge not only across disciplinary boundaries (e.g., geology, biology, physical oceanography, geochemistry and meteorology), but also across geographic boundaries (e.g., shelves, margins and the central Arctic Ocean) and temporal boundaries (e.g., paleo/geologic records, current process observations and future modeling studies). This interdisciplinary, international and integrated temporal approach of the ART Initiative will provide a means to better understand and predict change and ultimate responses in the Arctic Ocean system. More information about the ART Initiative can be found at www.aosb.org/art.html

Authorship in JASIS: A quantitative analysis

The researchers systematically examined authorship patterns of feature articles and brief communications in the Journal of the American Society for Information Science (JASIS), a leading professional publication in its field, from 1970 to 1996. Characteristics of authors, as opposed to the content of the journal and the domain of information science, serve as the focus of the study. Data on gender, academic or other professional affiliation, geographic location, and frequency of authorship were drawn from the JASIS articles themselves and tabulated both by individual years and over the entire span of the study. The study sought quantitative evidence of changing authorship patterns and the findings are explained in relation to previous authorship studies

CNS Recruitment of CD8+ T Lymphocytes Specific for a Peripheral Virus Infection Triggers Neuropathogenesis during Polymicrobial Challenge

Although viruses have been implicated in central nervous system (CNS) diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV) and peripherally restricted lymphocytic choriomeningitis virus (LCMV). While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35%) of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack

Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy

BACKGROUND: Cancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and preexisting cardiovascular disorders. These parameters incompletely account for substantial interindividual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM. METHODS: We studied 213 patients with CCM from 3 cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped adults with breast cancer (n=73), and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including 9 prespecified genes, were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas participants (n=2053), healthy volunteers (n=445), and an ancestry-matched reference population. Clinical characteristics and outcomes were assessed and stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice. RESULTS: CCM was diagnosed 0.4 to 9 years after chemotherapy; 90% of these patients received anthracyclines. Adult patients with CCM had cardiovascular risk factors similar to the US population. Among 9 prioritized genes, patients with CCM had more rare protein-altering variants than comparative cohorts ( P≤1.98e-04). Titin-truncating variants (TTNtvs) predominated, occurring in 7.5% of patients with CCM versus 1.1% of The Cancer Genome Atlas participants ( P=7.36e-08), 0.7% of healthy volunteers ( P=3.42e-06), and 0.6% of the reference population ( P=5.87e-14). Adult patients who had CCM with TTNtvs experienced more heart failure and atrial fibrillation ( P=0.003) and impaired myocardial recovery ( P=0.03) than those without. Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wild-type ( P=0.0004 and P<0.002, respectively). CONCLUSIONS: Unrecognized rare variants in cardiomyopathy-associated genes, particularly TTNtvs, increased the risk for CCM in children and adults, and adverse cardiac events in adults. Genotype, along with cumulative chemotherapy dosage and traditional cardiovascular risk factors, improves the identification of patients who have cancer at highest risk for CCM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01173341; AAML1031; NCT01371981.This work was supported in part by grants from the Instituto de Salud Carlos III (ISCIII) (PI15/01551, PI17/01941 and CB16/11/00432 to P.G-P. and L.A-P.), the Spanish Ministry of Economy and Competitiveness (SAF2015-71863-REDT to P.G-P.), the John S. LaDue Memorial Fellowship at Harvard Medical School (Y.K.), Wellcome Trust (107469/Z/15/Z to J.S.W.), Medical Research Council (intramural awards to S.A.C. and J.S.W; MR/M003191/1 to U.T), National Institute for Health Research Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College London (P.J.B., S.A.C., J.S.W.), National Institute for Health Research Biomedical Research Centre at Imperial College London Healthcare National Health Service Trust and Imperial College London (D.O.R., S.A.C., S.P., J.S.W.), Sir Henry Wellcome Postdoctoral Fellowship (C.N.T.), Rosetrees and Stoneygate Imperial College Research Fellowship (N.W.), Fondation Leducq (S.A.C., C.E.S., J.G.S.), Health Innovation Challenge Fund award from the Wellcome Trust and Department of Health (UK; HICF-R6-373; S.A.C., P.J.B., J.S. W.), the British Heart Foundation (NH/17/1/32725 to D.O.R.; SP/10/10/28431 to S.A.C), Alex’s Lemonade Stand Foundation (K.G.), National Institutes of Health (R.A.: U01CA097452, R01CA133881, and U01CA097452; Z.A.: R01 HL126797; B.K.: R01 HL118018 and K23-HL095661; J.G.S. and C.E.S.: 5R01HL080494, R01HL084553), and the Howard Hughes Medical Institute (C.E.S.). The Universitario Puerta de Hierro and Virgen de la Arrixaca Hospitals are members of the European Reference Network on Rare and Complex Diseases of the Heart (Guard-Heart; http://guard-heart.ern-net.eu). This publication includes independent research commissioned by the Health Innovation Challenge Fund (HICF), a parallel funding partnership between the Department of Health and Wellcome Trust. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Grants from ISCIII and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de I+D+I 2013-2016 – European Regional Development Fund (FEDER) “A way of making Europe”.S

Titin-truncating variants affect heart function in disease cohorts and the general population

Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ~1% of the general population, where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease