Scotland’s volatile political and electoral geography

PostprintNon peer reviewe

Social Affiliation and Contact Patterns Among White-tailed Deer in Disparate Landscapes: Implications for Disease Transmission

In social species, individuals contact members of the same group much more often than those of other groups, particularly for contacts that could directly transmit disease agents. This disparity in contact rates violates the assumptions of simple disease models, hinders disease spread between groups, and could decouple disease transmission from population density. Social behavior of white-tailed deer has important implications for the long-term dynamics and impact of diseases such as bovine tuberculosis and chronic wasting disease (CWD), so expanding our understanding of their social system is important. White-tailed deer form matrilineal groups, which inhabit stable home ranges that overlap somewhat with others—a pattern intermediate between mass-action and strict territoriality. To quantify how group membership affects their contact rates and document the spectrum of social affiliation, we analyzed location data from global positioning system (GPS) collars on female and juvenile white-tailed deer in 2 study areas: near Carbondale in forest-dominated southern Illinois (2002–2006) and near Lake Shelbyville in agriculture-dominated central Illinois (2006–2009). For each deer dyad (i.e., 2 individual deer with sufficient overlapping GPS data), we measured space-use overlap, correlation of movements, direct contact rate (simultaneous GPS locations \u3c 10 m apart), and indirect contact rate (GPS locations \u3c 10 m apart when offset by 1 or 3 days). Direct contact rates were substantially higher for within-group dyads than between-group dyads, but group membership had little apparent effect on indirect contact rates. The group membership effect on direct contact rates was strongest in winter and weakest in summer, with no apparent difference between study areas. Social affiliations were not dichotomous, with some deer dyads showing loose but positive affiliation. Even for obvious within-group dyads, their strength of affiliation fluctuated between years, seasons, and even days. Our findings highlight the poor fit between deer behavior and simple models of disease transmission and, combined with previous infection data, suggest that direct contact is the primary driver of CWD transmission among free living female and juvenile white-tailed deer

Community Seismic Network

The article describes the design of the Community Seismic Network, which is a dense open seismic network based on low cost sensors. The inputs are from sensors hosted by volunteers from the community by direct connection to their personal computers, or through sensors built into mobile devices. The server is cloud-based for robustness and to dynamically handle the load of impulsive earthquake events. The main product of the network is a map of peak acceleration, delivered within seconds of the ground shaking. The lateral variations in the level of shaking will be valuable to first responders, and the waveform information from a dense network will allow detailed mapping of the rupture process. Sensors in buildings may be useful for monitoring the state-of-health of the structure after major shaking

Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes.

Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony-stimulating factor (G-CSF) preserves β-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4-24 months) were randomized to ATG and pegylated G-CSF (ATG+G-CSF) (N = 17) or placebo (N = 8). Primary outcomes included C-peptide area under the curve (AUC) following a mixed-meal tolerance test (MMTT) and flow cytometry. "Responders" (12-month C-peptide ≥ baseline), "super responders" (24-month C-peptide ≥ baseline), and "nonresponders" (12-month C-peptide < baseline) were evaluated for biomarkers of outcome. At 24 months, MMTT-stimulated AUC C-peptide was not significantly different in ATG+G-CSF (0.49 nmol/L/min) versus placebo (0.29 nmol/L/min). Subjects treated with ATG+G-CSF demonstrated reduced CD4+ T cells and CD4+/CD8+ T-cell ratio and increased CD16+CD56hi natural killer cells (NK), CD4+ effector memory T cells (Tem), CD4+PD-1+ central memory T cells (Tcm), Tcm PD-1 expression, and neutrophils. FOXP3+Helios+ regulatory T cells (Treg) were elevated in ATG+G-CSF subjects at 6, 12, and 18 but not 24 months. Immunophenotyping identified differential HLA-DR expression on monocytes and NK and altered CXCR3 and PD-1 expression on T-cell subsets. As such, a group of metabolic and immunological responders was identified. A phase II study of ATG+G-CSF in patients with new-onset type 1 diabetes is ongoing and may support ATG+G-CSF as a prevention strategy in high-risk subjects

Acute social isolation alters neurogenomic state in songbird forebrain

Prolonged social isolation has negative effects on brain and behavior in humans and other social organisms, but neural mechanisms leading to these effects are not understood. Here we tested the hypothesis that even brief periods of social isolation can alter gene expression and DNA methylation in higher cognitive centers of the brain, focusing on the auditory/associative forebrain of the highly social zebra finch. Using RNA sequencing, we first identified genes that individually increase or decrease expression after isolation and observed general repression of gene sets annotated for neurotrophin pathways and axonal guidance functions. We then pursued 4 genes of large effect size: EGR1 and BDNF (decreased by isolation) and FKBP5 and UTS2B (increased). By in situ hybridization, each gene responded in different cell subsets, arguing against a single cellular mechanism. To test whether effects were specific to the social component of the isolation experience, we compared gene expression in birds isolated either alone or with a single familiar partner. Partner inclusion ameliorated the effect of solo isolation on EGR1 and BDNF, but not on FKBP5 and UTS2B nor on circulating corticosterone. By bisulfite sequencing analysis of auditory forebrain DNA, isolation caused changes in methylation of a subset of differentially expressed genes, including BDNF. Thus, social isolation has rapid consequences on gene activity in a higher integrative center of the brain, triggering epigenetic mechanisms that may influence processing of ongoing experience.Peer reviewe

Alphavirus replicon-based enhancement of mucosal and systemic immunity is linked to the innate response generated by primary immunization

Venezuelan equine encephalitis virus replicon particles (VRP) function as an effective systemic, cellular and mucosal adjuvant when codelivered with antigen, and show promise for use as a component in new and existing human vaccine formulations. We show here that VRP are effective at low dose and by intramuscular delivery, two useful features for implementation of VRP as a vaccine adjuvant. In mice receiving a prime and boost with antigen, we found that VRP are required in prime only to produce a full adjuvant effect. This outcome indicates that the events triggered during prime with VRP are sufficient to establish the nature and magnitude of the immune response to a second exposure to antigen. Events induced by VRP in the draining lymph node after prime include robust secretion of many inflammatory cytokines, upregulation of CD69 on leukocytes, and increased cellularity, with a disproportionate increase of a cell population expressing CD11c, CD11b, and F4/80. We show that antigen delivered 24 hours after administration of VRP does not benefit from an adjuvant effect, indicating that the events which are critical to VRP-mediated adjuvant activity occur within the first 24 hours. Further studies of the events induced by VRP will help elucidate the mechanism of VRP adjuvant activity and will advance the safe implementation of this adjuvant in human vaccines

Challenges and directions in studying cell-cell communication by extracellular vesicles

Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. They have important roles in numerous physiological and pathological processes, and show considerable promise as novel biomarkers of disease, as therapeutic agents and as drug delivery vehicles. Intriguingly, however, understanding of the cellular and molecular mechanisms that govern the many observed functions of EVs remains far from comprehensive, at least partly due to technical challenges in working with these small messengers. Here, we highlight areas of consensus as well as contentious issues in our understanding of the intracellular and intercellular journey of EVs: from biogenesis, release and dynamics in the extracellular space, to interaction with and uptake by recipient cells. We define knowledge gaps, identify key questions and challenges, and make recommendations on how to address these

Manual / Issue 3 / Circus

Manual, a journal about art and its making. Circus. The third issue centers on the theme of Circus. Includes analyses of various pieces in the museum\u27s archive, a fold-out poster by Jim Drain, and a selection of artworks owned by the museum that loosely address said theme. Softcover, 62 pages. Published 2014 by the RISD Museum. Manual 3 (Circus) contributors include Gina Borromeo, Alison W. Chang, Michelle Clayton, Jim Drain, Daniel Heyman, Andrew Martinez, Ellen McBreen, Thangam Ravindranathan, Rebecca Schneider, Susan Smulyan, and Gwen Strahle.https://digitalcommons.risd.edu/risdmuseum_journals/1002/thumbnail.jp

Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation.

The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation