The emerging zika virus epidemic in the Americas: Research priorities

On February 1, 2016, the World Health Organization declared a “public health emergency of international concern” regarding neurological disorders associated with the rapid emergence of Zika virus (ZIKV) in the Americas. Since being detected in Brazil in early 2015, ZIKV has spread extensively, with most countries in Latin America and the Caribbean now reporting local transmission of the virus. An association between congenital ZIKV infection and birth defects, most prominently microcephaly, has prompted intense concern among health officials and the public

Variation in paranasal pneumatisation between Mid-Late Pleistocene hominins

There is considerable variation in mid-late Pleistocene hominin paranasal sinuses, and in some taxa distinctive craniofacial shape has been linked to sinus size. Extreme frontal sinus size has been reported in mid-Pleistocene specimens often classified as Homo heidelbergensis, and Neanderthal sinuses are said to be distinctively large, explaining diagnostic Neanderthal facial shape. Here, the sinuses of fossil hominins attributed to several mid-late Pleistocene taxa were compared to those of recent H. sapiens. The sinuses were investigated to clarify differences in the extent of pneumatisation within this group and the relationship between sinus size and craniofacial variation in hominins from this time period. Frontal and maxillary sinus volumes were measured from CT data, and geometric morphometric methods were used to identify and analyse shape variables associated with sinus volume. Some mid

Runaway Events Dominate the Heavy Tail of Citation Distributions

Statistical distributions with heavy tails are ubiquitous in natural and social phenomena. Since the entries in heavy tail have disproportional significance, the knowledge of its exact shape is very important. Citations of scientific papers form one of the best-known heavy tail distributions. Even in this case there is a considerable debate whether citation distribution follows the log-normal or power-law fit. The goal of our study is to solve this debate by measuring citation distribution for a very large and homogeneous data. We measured citation distribution for 418,438 Physics papers published in 1980-1989 and cited by 2008. While the log-normal fit deviates too strong from the data, the discrete power-law function with the exponent $\gamma=3.15$ does better and fits 99.955% of the data. However, the extreme tail of the distribution deviates upward even from the power-law fit and exhibits a dramatic "runaway" behavior. The onset of the runaway regime is revealed macroscopically as the paper garners 1000-1500 citations, however the microscopic measurements of autocorrelation in citation rates are able to predict this behavior in advance.Comment: 6 pages, 5 Figure

Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFbeta), angiostatin, and endostatin are increased in radiotherapy-induced gastrointestinal toxicity

Radiotherapy-induced gut toxicity (RIGT) is a debilitating effect of radiotherapy for cancer, often resulting in significant diarrhoea and pain. Previous studies have highlighted roles of the intestinal microvasculature and matrix metalloproteinases (MMPs) in the development of RIGT. We hypothesized vascular mediators would be significantly altered in a dark agouti (DA) rat model of RIGT. Additionally, we aimed to assess the effect of MMP-2 and -9 inhibition on the response of tumour-associated microvascular endothelial cells (TAMECs) to radiation.Dark Agouti (DA) rats were administered 2.5 Gy abdominal irradiation (3 times/week over 6 weeks). Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), von Willebrand factor (VWF), angiostatin, and endostatin expression was assessed at 3, 6 and 15 weeks. Additionally, DA rat mammary adenocarcinoma tumour-associated microvascular endothelial cells (TAMECs) were used to assess the effects of radiation (12 Gy) and the MMP inhibitor SB-3CT on MMP, VEGF, and TGFβ expression, and cell viability.VEGF mRNA expression was significantly increased in the colon at week 15 (p = 0.0012), and TGFβ mRNA expression was significantly increased in both the jejunum and colon at week 3 (p = 0.0280, and p = 0.0310, respectively). Endostatin immunostaining was significantly increased at week 3 (p = 0.0046), and angiostatin at 3 and 6 weeks (p = 0.0022, and p = 0.0135, respectively). MMP-2 and -9 mRNA and total protein levels were significantly increased following irradiation of TAMECs. Although this increase was significantly attenuated by SB-3CT, it did not significantly alter endothelial cell viability or VEGF and TGFβ mRNA expression.Findings of this study support the involvement of VEGF, TGFβ, angiostatin, endostatin, and MMP-2 in the pathobiology of RIGT. However, the relationship between these mediators is complex and needs further investigation to improve understanding of their therapeutic potential in RIGT.Romany L. Stansborough, Emma H. Bateman, Noor Al-Dasooqi, Joanne M. Bowen, Anthony Wignall, Dorothy M. Keefe, Ann S. Yeoh, Richard M. Logan, Eric E. K. Yeoh, Andrea M. Stringer and Rachel J. Gibso

Climate change research and action must look beyond 2100

Anthropogenic activity is changing Earth's climate and ecosystems in ways that are potentially dangerous and disruptive to humans. Greenhouse gas concentrations in the atmosphere continue to rise, ensuring that these changes will be felt for centuries beyond 2100, the current benchmark for projection. Estimating the effects of past, current, and potential future emissions to only 2100 is therefore short-sighted. Critical problems for food production and climate-forced human migration are projected to arise well before 2100, raising questions regarding the habitability of some regions of the Earth after the turn of the century. To highlight the need for more distant horizon scanning, we model climate change to 2500 under a suite of emission scenarios and quantify associated projections of crop viability and heat stress. Together, our projections show global climate impacts increase significantly after 2100 without rapid mitigation. As a result, we argue that projections of climate and its effects on human well-being and associated governance and policy must be framed beyond 2100

Therapeutic Potential of a Novel Vitamin D3 Oxime Analogue, VD1-6, with CYP24A1 Enzyme Inhibitory Activity and Negligible Vitamin D Receptor Binding

Abstract: The regulation of vitamin D3 actions in humans occurs mainly through the Cytochrome P450 24-hydroxylase (CYP24A1) enzyme activity. CYP24A1 hydroxylates both 25-hydroxycholecalciferol (25(OH)D3) and 1,25-dihydroxycholecalciferol (1,25(OH)2D3), which is the first step of vitamin D catabolism. An abnormal status of the upregulation of CYP24A1 occurs in many diseases, including chronic kidney disease (CKD). CYP24A1 upregulation in CKD and diminished activation of vitamin D3 contribute to secondary hyperparathyroidism (SHPT), progressive bone deterioration, and soft tissue and cardiovascular calcification. Previous studies have indicated that CYP24A1 inhibition may be an effective strategy to increase endogenous vitamin D activity and decrease SHPT. This study has designed and synthesized a novel C-24 O-methyloxime analogue of vitamin D3 (VD1-6) to have specific CYP24A1 inhibitory properties. VD1-6 did not bind to the vitamin D receptor (VDR) in concentrations up to 10-7 M, assessed by a VDR binding assay. The absence of VDR binding by VD1-6 was confirmed in human embryonic kidney HEK293T cultures through the lack of CYP24A1 induction. However, in silico docking experiments demonstrated that VD1-6 was predicted to have superior binding to CYP24A1, when compared to that of 1,25(OH)2D3. The inhibition of CYP24A1 by VD1-6 was also evident by the synergistic potentiation of 1,25(OH)2D3-mediated transcription and reduced 1,25(OH)2D3 catabolism over 24 h. A further indication of CYP24A1 inhibition by VD1-6 was the reduced accumulation of the 24,25(OH)D3, the first metabolite of 25(OH)D catabolism by CYP24A1. Our findings suggest the potent CYP24A1 inhibitory properties of VD1-6 and its potential for testing as an alternative therapeutic candidate for treating SHPT.Ali K. Alshabrawy, Yingjie Cui, Cyan Sylvester, Dongqing Yang, Emilio S. Petito, Kate R. Barratt, Rebecca K. Sawyer, Jessica K. Heatlie, Ruhi Polara, Matthew J. Sykes, Gerald J. Atkins, Shane M. Hickey, Michael D. Wiese, Andrea M. Stringer, Zhaopeng Liu, and Paul H. Anderso

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters