Aberrant Proliferation in CXCR7+ Endothelial Cells via Degradation of the Retinoblastoma Protein

Angiogenesis is a critical factor in the growth and dissemination of solid tumors. Indeed, tumor vasculature is abnormal and contributes to the development and spread of malignancies by creating a hostile microenvironment. The alternative SDF-1/CXCL12 receptor, CXCR7, is frequently and specifically expressed in tumor-associated vessels. In this study, we examine the role of endothelium-expressed CXCR7 in tumor vascular dysfunction by specifically examining the contribution of CXCR7 to endothelial cell (EC) proliferation. We demonstrate that CXCR7 expression is sufficient to drive post-confluent growth in EC cultures. Further, we provide a novel mechanism for CXCR7-mediated proliferation via proteasomal degradation of the tumor suppressor protein Rb. These findings identify a heretofore unappreciated role for CXCR7 in vascular dysfunction and confirm this receptor as a plausible target for anti-tumor therapy

Single transit candidates from K2 : detection and period estimation

Photometric surveys such as Kepler have the precision to identify exoplanet and eclipsing binary candidates from only a single transit. K2, with its 75 d campaign duration, is ideally suited to detect significant numbers of single-eclipsing objects. Here we develop a Bayesian transit-fitting tool (‘Namaste: An Mcmc Analysis of Single Transit Exoplanets’) to extract orbital information from single transit events. We achieve favourable results testing this technique on known Kepler planets, and apply the technique to seven candidates identified from a targeted search of K2 campaigns 1, 2 and 3. We find EPIC203311200 to host an excellent exoplanet candidate with a period, assuming zero eccentricity, of 540+410 −230 d and a radius of 0.51 ± 0.05RJup. We also find six further transit candidates for which more follow-up is required to determine a planetary origin. Such a technique could be used in the future with TESS, PLATO and ground-based photometric surveys such as NGTS, potentially allowing the detection of planets in reach of confirmation by Gaia

The role of taxonomic expertise in interpretation of metabarcoding studies

Abstract The performance of DNA metabarcoding approaches for characterizing biodiversity can be influenced by multiple factors. Here, we used morphological assessment of taxa in zooplankton samples to develop a large barcode database and to assess the congruence of taxonomic identification with metabarcoding under different conditions. We analysed taxonomic assignment of metabarcoded samples using two genetic markers (COI, 18S V1–2), two types of clustering into molecular operational taxonomic units (OTUs, ZOTUs), and three methods for taxonomic assignment (RDP Classifier, BLASTn to GenBank, BLASTn to a local barcode database). The local database includes 1042 COI and 1108 18S (SSU) barcode sequences, and we added new high-quality sequences to GenBank for both markers, including 109 contributions at the species level. The number of phyla detected and the number of taxa identified to phylum varied between a genetic marker and among the three methods used for taxonomic assignments. Blasting the metabarcodes to the local database generated multiple unique contributions to identify OTUs and ZOTUs. We argue that a multi-marker approach combined with taxonomic expertise to develop a curated, vouchered, local barcode database increases taxon detection with metabarcoding, and its potential as a tool for zooplankton biodiversity surveys

Barriers to Treatment for Female Problem Gamblers: A UK Perspective

There is a paucity of research in the UK which examines problem gambling and that which does exist is mainly quantitative, focuses on male samples and fails to look at treatment seeking populations or obstacles preventing problem gamblers from seeking treatment. This paper presents findings from part of a larger qualitative study that explored the experience of treatment for female problem gamblers. Data were collected using semi-structured interviews with eight women who had received individual cognitive-behavioural therapy in the National Health Service for their gambling problem. An interpretative phenomenological analysis approach was applied in the research process, identifying three main themes, of which the subtheme ‘Barriers to Treatment’ is examined here. Internal and external barriers to treatment organically emerged in all female participants’ accounts and appear to have an impact on service utilisation. Input directly from gamblers can be combined with findings from other studies to devise better ways of reaching female problem gamblers. A better understanding of barriers to treatment can also provide valuable direction for future research and suggest applications in clinical service provision and treatment planning

A 3-O-sulfated heparan sulfate dodecasaccharide (12-mer) suppresses thromboinflammation and attenuates early organ injury following trauma and hemorrhagic shock

Introduction Dysregulated inflammation and coagulation are underlying mechanisms driving organ injury after trauma and hemorrhagic shock. Heparan sulfates, cell surface glycosaminoglycans abundantly expressed on the endothelial surface, regulate a variety of cellular processes. Endothelial heparan sulfate containing a rare 3-O-sulfate modification on a glucosamine residue is anticoagulant and anti-inflammatory through high-affinity antithrombin binding and sequestering of circulating damage-associated molecular pattern molecules. Our goal was to evaluate therapeutic potential of a synthetic 3-O-sulfated heparan sulfate dodecasaccharide (12-mer, or dekaparin) to attenuate thromboinflammation and prevent organ injury. Methods Male Sprague-Dawley rats were pre-treated subcutaneously with vehicle (saline) or dekaparin (2 mg/kg) and subjected to a trauma/hemorrhagic shock model through laparotomy, gut distention, and fixed-pressure hemorrhage. Vehicle and dekaparin-treated rats were resuscitated with Lactated Ringer’s solution (LR) and compared to vehicle-treated fresh-frozen-plasma-(FFP)-resuscitated rats. Serial blood samples were collected at baseline, after induction of shock, and 3 hours after fluid resuscitation to measure hemodynamic and metabolic shock indicators, inflammatory mediators, and thrombin-antithrombin complex formation. Lungs and kidneys were processed for organ injury scoring and immunohistochemical analysis to quantify presence of neutrophils. Results Induction of trauma and hemorrhagic shock resulted in significant increases in thrombin-antithrombin complex, inflammatory markers, and lung and kidney injury scores. Compared to vehicle, dekaparin treatment did not affect induction, severity, or recovery of shock as indicated by hemodynamics, metabolic indicators of shock (lactate and base excess), or metrics of bleeding, including overall blood loss, resuscitation volume, or hematocrit. While LR-vehicle-resuscitated rodents exhibited increased lung and kidney injury, administration of dekaparin significantly reduced organ injury scores and was similar to organ protection conferred by FFP resuscitation. This was associated with a significant reduction in neutrophil infiltration in lungs and kidneys and reduced lung fibrin deposition among dekaparin-treated rats compared to vehicle. No differences in organ injury, neutrophil infiltrates, or fibrin staining between dekaparin and FFP groups were observed. Finally, dekaparin treatment attenuated induction of thrombin-antithrombin complex and inflammatory mediators in plasma following trauma and hemorrhagic shock. Conclusion Anti-thromboinflammatory properties of a synthetic 3-O-sulfated heparan sulfate 12-mer, dekaparin, could provide therapeutic benefit for mitigating organ injury following major trauma and hemorrhagic shock

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

DNA Methylation Analysis of Bone Marrow Cells at Diagnosis of Acute Lymphoblastic Leukemia and at Remission

To detect genes with CpG sites that display methylation patterns that are characteristic of acute lymphoblastic leukemia (ALL) cells, we compared the methylation patterns of cells taken at diagnosis from 20 patients with pediatric ALL to the methylation patterns in mononuclear cells from bone marrow of the same patients during remission and in non-leukemic control cells from bone marrow or blood. Using a custom-designed assay, we measured the methylation levels of 1,320 CpG sites in regulatory regions of 413 genes that were analyzed because they display allele-specific gene expression (ASE) in ALL cells. The rationale for our selection of CpG sites was that ASE could be the result of allele-specific methylation in the promoter regions of the genes. We found that the ALL cells had methylation profiles that allowed distinction between ALL cells and control cells. Using stringent criteria for calling differential methylation, we identified 28 CpG sites in 24 genes with recurrent differences in their methylation levels between ALL cells and control cells. Twenty of the differentially methylated genes were hypermethylated in the ALL cells, and as many as nine of them (AMICA1, CPNE7, CR1, DBC1, EYA4, LGALS8, RYR3, UQCRFS1, WDR35) have functions in cell signaling and/or apoptosis. The methylation levels of a subset of the genes were consistent with an inverse relationship with the mRNA expression levels in a large number of ALL cells from published data sets, supporting a potential biological effect of the methylation signatures and their application for diagnostic purposes

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The Effects of Biogeography on Ant Diversity and Activity on the Boston Harbor Islands, Massachusetts, U.S.A

Many studies have examined how island biogeography affects diversity on the scale of island systems. In this study, we address how diversity varies over very short periods of time on individual islands. To do this, we compile an inventory of the ants living in the Boston Harbor Islands National Recreation Area, Boston, Massachusetts, USA using data from a five-year All Taxa Biodiversity Inventory of the region's arthropods. Consistent with the classical theory of island biogeography, species richness increased with island size, decreased with island isolation, and remained relatively constant over time. Additionally, our inventory finds that almost half of the known Massachusetts ant fauna can be collected in the BHI, and identifies four new species records for Massachusetts, including one new to the United States, Myrmica scabrinodis. We find that the number of species actually active on islands depended greatly on the timescale under consideration. The species that could be detected during any given week of sampling could by no means account for total island species richness, even when correcting for sampling effort. Though we consistently collected the same number of species over any given week of sampling, the identities of those species varied greatly between weeks. This variation does not result from local immigration and extinction of species, nor from seasonally-driven changes in the abundance of individual species, but rather from weekly changes in the distribution and activity of foraging ants. This variation can be upwards of 50% of ant species per week. This suggests that numerous ant species on the BHI share the same physical space at different times. This temporal partitioning could well explain such unexpectedly high ant diversity in an isolated, urban site