The Heterogeneity, Distribution, and Environmental Associations of Borrelia burgdorferi Sensu Lato, the Agent of Lyme Borreliosis, in Scotland

Genospecies controls were obtained from the laboratory of Dr. Muriel Cornet at the Institut Pasteur, Paris. We thank Bob Furness for collecting ticks from passerine birds, Steph Vollmer for processing the samples from one site, E. Packer, A. Wiebe, J. Low, E. Stephen, and J. Arthur for help collecting ticks, Kenny Raey for laboratory assistance, and Jackie Potts for statistical advice. Marianne C. James was funded by a Biotechnology and Biological Sciences Research Council (BBSRC) Doctoral Training Grant with CASE support from the Macaulay Development Trust awarded to Alan S. Bowman and Lucy Gilbert. Lucy Gilbert was supported by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS).Peer reviewedPublisher PD

The Application of Integrated Knowledge-based Systems for the Biomedical Risk Assessment Intelligent Network (BRAIN)

One of NASA's goals for long duration space flight is to maintain acceptable levels of crew health, safety, and performance. One way of meeting this goal is through the Biomedical Risk Assessment Intelligent Network (BRAIN), an integrated network of both human and computer elements. The BRAIN will function as an advisor to flight surgeons by assessing the risk of in-flight biomedical problems and recommending appropriate countermeasures. This paper describes the joint effort among various NASA elements to develop BRAIN and an Infectious Disease Risk Assessment (IDRA) prototype. The implementation of this effort addresses the technological aspects of the following: (1) knowledge acquisition; (2) integration of IDRA components; (3) use of expert systems to automate the biomedical prediction process; (4) development of a user-friendly interface; and (5) integration of the IDRA prototype and Exercise Countermeasures Intelligent System (ExerCISys). Because the C Language, CLIPS (the C Language Integrated Production System), and the X-Window System were portable and easily integrated, they were chosen as the tools for the initial IDRA prototype. The feasibility was tested by developing an IDRA prototype that predicts the individual risk of influenza. The application of knowledge-based systems to risk assessment is of great market value to the medical technology industry

Genome-wide association and genome partitioning reveal novel genomic regions underlying variation in gastrointestinal nematode burden in a wild bird

Acknowledgements This study was funded by a BBSRC studentship (MA Wenzel) and NERC grants NE/H00775X/1 and NE/D000602/1 (SB Piertney). The authors are grateful to Fiona Leckie, Andrew MacColl, Jesús Martínez-Padilla, François Mougeot, Steve Redpath, Pablo Vergara† and Lucy M.I. Webster for samples; Keliya Bai, Daisy Brickhill, Edward Graham, Alyson Little, Daniel Mifsud, Lizzie Molyneux and Mario Röder for fieldwork assistance; Gillian Murray-Dickson and Laura Watt for laboratory assistance; Heather Ritchie for helpful comments on manuscript drafts; and all estate owners, factors and keepers for access to field sites, most particularly Stuart Young and Derek Calder (Edinglassie), Simon Blackett, Jim Davidson and Liam Donald (Invercauld and Glas Choille), Richard Cooke and Fred Taylor† (Invermark) and T. Helps (Catterick).Peer reviewedPostprin

The role of parasite-driven selection in shaping landscape genomic structure in red grouse (Lagopus lagopus scotica)

Acknowledgements This study was funded by a BBSRC studentship (MAW) and NERC grants NE/H00775X/1 and NE/D000602/1 (SBP). The authors are grateful to Mario Röder and Keliya Bai for fieldwork assistance, and all estate owners, factors and keepers for access to field sites, most particularly MJ Taylor and Mike Nisbet (Airlie), Neil Brown (Allargue), RR Gledson and David Scrimgeour (Delnadamph), Andrew Salvesen and John Hay (Dinnet), Stuart Young and Derek Calder (Edinglassie), Kirsty Donald and David Busfield (Glen Dye), Neil Hogbin and Ab Taylor (Glen Muick), Alistair Mitchell (Glenlivet), Simon Blackett, Jim Davidson and Liam Donald (Invercauld), Richard Cooke and Fred Taylor† (Invermark), Shaila Rao and Christopher Murphy (Mar Lodge), and Ralph Peters and Philip Astor (Tillypronie). S.B.P. and S.M.R. conceived and designed the study. M.A.W. performed field and laboratory work. A.D. and M.C.J. developed SNP markers. M.A.W. analysed the data. M.A.W. and S.B.P. wrote the manuscript.Peer reviewedPostprin

TGF-β Suppresses β-Catenin-Dependent Tolerogenic Activation Program in Dendritic Cells

The mechanisms that underlie the critical dendritic cell (DC) function in maintainance of peripheral immune tolerance are incompletely understood, although the β-catenin signaling pathway is critical for this role. The molecular details by which β-catenin signaling is regulated in DCs are unknown. Mechanical disruption of murine bone marrow-derived DC (BMDC) clusters activates DCs while maintaining their tolerogenic potential and this activation is associated with β-catenin signaling, providing a useful model with which to explore tolerance-associated β-catenin signaling in DCs. In this report, we demonstrate novel molecular features of the signaling events that control DC activation in response to mechanical stimulation. Non-canonical β-catenin signaling is an essential component of this tolerogenic activation and is modulated by adhesion molecules, including integrins. This unique β-catenin-dependent signaling pathway is constitutively active at low levels, suggesting that mechanical stimulation is not necessarily required for induction of this unique activation program. We additionally find that the immunomodulatory cytokine TGF-β antagonizes β-catenin in DCs, thereby selectively suppressing signaling associated with tolerogenic DC activation while having no impact on LPS-induced, β-catenin-independent immunogenic activation. These findings provide new molecular insight into the regulation of a critical signaling pathway for DC function in peripheral immune tolerance

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Combined effects of crude oil exposure and warming on eggs and larvae of an arctic forage fish

Climate change, along with environmental pollution, can act synergistically on an organism to amplify adverse effects of exposure. The Arctic is undergoing profound climatic change and an increase in human activity, resulting in a heightened risk of accidental oil spills. Embryos and larvae of polar cod (Boreogadus saida), a key Arctic forage fish species, were exposed to low levels of crude oil concurrently with a 2.3 °C increase in water temperature. Here we show synergistic adverse effects of increased temperature and crude oil exposure on early life stages documented by an increased prevalence of malformations and mortality in exposed larvae. The combined effects of these stressors were most prevalent in the first feeding larval stages despite embryonic exposure, highlighting potential long-term consequences of exposure for survival, growth, and reproduction. Our findings suggest that a warmer Arctic with greater human activity will adversely impact early life stages of this circumpolar forage fish

Cardiac sodium channel inhibition by lamotrigine: in vitro characterization and clinical implications

Lamotrigine, approved for use as an antiseizure medication (ASM) as well as the treatment of bipolar disorder, inhibits sodium channels in the brain to reduce repetitive neuronal firing and pathological release of glutamate. The shared homology of sodium channels and lack of selectivity associated with channel blocking agents can cause slowing of cardiac conduction and increased proarrhythmic potential. The Vaughan-Williams classification system differentiates sodium channel blockers using biophysical properties of binding. As such, Class Ib inhibitors including mexiletine do not slow cardiac conduction as measured by the electrocardiogram (ECG), at therapeutically relevant exposure. Our goal was to characterize the biophysical properties of NaV 1.5 block and to support the observed clinical safety of lamotrigine. We used HEK-293 cells stably expressing the hNaV 1.5 channel and voltage clamp electrophysiology to quantify the potency (IC50 ) against peak and late channel current, on-/off-rate binding kinetics, voltage-dependence and tonic block of the cardiac sodium channel by lamotrigine; and compared to clinically relevant Class Ia (quinidine), Ib (mexiletine) and Ic (flecainide) inhibitors. Lamotrigine blocked peak and late NaV 1.5 current at therapeutically relevant exposure, with rapid kinetics and biophysical properties similar to the Class Ib inhibitor mexiletine. However, no clinically meaningful prolongation in QRS or PR interval was observed in healthy subjects in a new analysis of a previously reported thorough QT clinical trial (SCA104648). In conclusion, the weak NaV 1.5 block and rapid kinetics do not translate into clinically relevant conduction slowing at therapeutic exposure and support the clinical safety of lamotrigine in patients suffering from epilepsy and bipolar disorder

Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy

Aim: To investigate whether brain volumes were reduced in children aged 6 to 8 years without cerebral palsy, who underwent therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (patients), and matched controls, and to examine the relation between subcortical volumes and functional outcome.   Method: We measured regional brain volumes in 31 patients and 32 controls (median age 7 years and 7 years 2 months respectively) from T1-weighted magnetic resonance imaging (MRI). We assessed cognition using the Wechsler Intelligence Scales for Children, Fourth Edition and motor ability using the Movement Assessment Battery for Children, Second Edition (MABC-2).  Results: Patients had lower volume of whole-brain grey matter, white matter, pallidi, hippocampi, and thalami than controls (false discovery rate-corrected p < 0.05). Differences in subcortical grey-matter volumes were not independent of total brain volume (TBV). In patients, hippocampal and thalamic volumes correlated with full-scale IQ (hippocampi, r = 0.477, p = 0.010; thalami, r = 0.452, p = 0.016) and MABC-2 total score (hippocampi, r = 0.526, p = 0.004; thalami, r = 0.505, p = 0.006) independent of age, sex, and TBV. No significant correlations were found in controls. In patients, cortical injury on neonatal MRI was associated with reduced volumes of hippocampi (p = 0.001), thalami (p = 0.002), grey matter (p = 0.015), and white matter (p = 0.013).  Interpretation: Children who underwent therapeutic hypothermia have reduced whole-brain grey and white-matter volumes, with associations between hippocampal and thalamic volumes and functional outcomes