T-Cell Responses to the M3 Immune Evasion Protein of Murid Gammaherpesvirus 68 Are Partially Protective and Induced with Lytic Antigen Kinetics

DNA vaccination with the M3 gene, encoding an immune evasion molecule expressed during both the acute lytic and persistent phases of murid gammaherpesvirus 68 infection, yielded a significantly lower titer of virus in the lung than controls. The protection seen was dependent on T cells, and we mapped an epitope recognized by CD8 T cells. The immune response to this epitope follows the same kinetics as lytic cycle antigens, despite the fact that this gene is expressed in both lytic and persistent stages of infection. This has important implications for our understanding of T-cell responses to putative latency-associated gammaherpesvirus proteins and how vaccination may improve control of these viruses

Environmental DNA for the enumeration and management of Pacific salmon

Pacific salmon are a keystone resource in Alaska, generating annual revenues of well over ~US$500 million/yr. Due to their anadromous life history, adult spawners distribute amongst thousands of streams, posing a huge management challenge. Currently, spawners are enumerated at just a few streams because of reliance on human counters and, rarely, sonar. The ability to detect organisms by shed tissue (environmental DNA, eDNA) promises a more efficient counting method. However, although eDNA correlates generally with local fish abundances, we do not know if eDNA can accurately enumerate salmon. Here we show that daily, and near‐daily, flow‐corrected eDNA rate closely tracks daily numbers of returning sockeye and coho spawners and outmigrating sockeye smolts. eDNA thus promises accurate and efficient enumeration, but to deliver the most robust numbers will need higher‐resolution stream‐flow data, at‐least‐daily sampling, and a focus on species with simple life histories, since shedding rate varies amongst jacks, juveniles, and adults

Citizen Participation in Urban Services: the Administration of a Community-Based Crime Prevention Program

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68929/2/10.1177_089976407800700105.pd

Equations for the estimation of strong ground motions from shallow crustal earthquakes using data from Europe and the Middle East : vertical peak ground acceleration and spectral acceleration

This article presents equations for the estimation of vertical strong ground motions caused by shallow crustal earthquakes with magnitudes M w 5 and distance to the surface projection of the fault less than 100km. These equations were derived by weighted regression analysis, used to remove observed magnitude-dependent variance, on a set of 595 strong-motion records recorded in Europe and the Middle East. Coefficients are included to model the effect of local site effects and faulting mechanism on the observed ground motions. The equations include coefficients to model the observed magnitude-dependent decay rate. The main findings of this study are that: short-period ground motions from small and moderate magnitude earthquakes decay faster than the commonly assumed 1/r, the average effect of differing faulting mechanisms is similar to that observed for horizontal motions and is not large and corresponds to factors between 0.7 (normal and odd) and 1.4 (thrust) with respect to strike-slip motions and that the average long-period amplification caused by soft soil deposits is about 2.1 over those on rock sites

Discovery of a nanodiamond-rich layer in the Greenland ice sheet

We report the discovery in the Greenland ice sheet of a discrete layer of free nanodiamonds (NDs) in very high abundances, implying most likely either an unprecedented influx of extraterrestrial (ET) material or a cosmic impact event that occurred after the last glacial episode. From that layer, we extracted n-diamonds and hexagonal diamonds (lonsdaleite), an accepted ET impact indicator, at abundances of up to about 5!106 times background levels in adjacent younger and older ice. The NDs in the concentrated layer are rounded, suggesting they most likely formed during a cosmic impact through some process similar to carbon-vapor deposition or high-explosive detonation. This morphology has not been reported previously in cosmic material, but has been observed in terrestrial impact material. This is the first highly enriched, discrete layer of NDs observed in glacial ice anywhere, and its presence indicates that ice caps are important archives of ET events of varying magnitudes. Using a preliminary ice chronology based on oxygen isotopes and dust stratigraphy, the ND-rich layer appears to be coeval with ND abundance peaks reported at numerous North American sites in a sedimentary layer, the Younger Dryas boundary layer (YDB), dating to 12.9 0.1 ka. However, more investigation is needed to confirm this association

Modelling chemistry in the nocturnal boundary layer above tropical rainforest and a generalised effective nocturnal ozone deposition velocity for sub-ppbv NOx conditions

Measurements of atmospheric composition have been made over a remote rainforest landscape. A box model has previously been demonstrated to model the observed daytime chemistry well. However the box model is unable to explain the nocturnal measurements of relatively high [NO] and [O3], but relatively low observed [NO2]. It is shown that a one-dimensional (1-D) column model with simple O3 -NOx chemistry and a simple representation of vertical transport is able to explain the observed nocturnal concentrations and predict the likely vertical profiles of these species in the nocturnal boundary layer (NBL). Concentrations of tracers carried over from the end of the night can affect the atmospheric chemistry of the following day. To ascertain the anomaly introduced by using the box model to represent the NBL, vertically-averaged NBL concentrations at the end of the night are compared between the 1-D model and the box model. It is found that, under low to medium [NOx] conditions (NOx <1 ppbv), a simple parametrisation can be used to modify the box model deposition velocity of ozone, in order to achieve good agreement between the box and 1-D models for these end-of-night concentrations of NOx and O3. This parametrisation would could also be used in global climate-chemistry models with limited vertical resolution near the surface. Box-model results for the following day differ significantly if this effective nocturnal deposition velocity for ozone is implemented; for instance, there is a 9% increase in the following day’s peak ozone concentration. However under medium to high [NOx] conditions (NOx > 1 ppbv), the effect on the chemistry due to the vertical distribution of the species means no box model can adequately represent chemistry in the NBL without modifying reaction rate constants

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease

Polymorphisms of an Innate Immune Gene, Toll-Like Receptor 4, and Aggressive Prostate Cancer Risk: A Systematic Review and Meta-Analysis

Background: Toll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews. Methods: We performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls. Results: Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity. Conclusions: TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa

Prediction of individual genetic risk to prostate cancer using a polygenic score

BACKGROUND Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P-=-0.0012) and the net reclassification index with 0.21 (P-=-8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction