bluuebunny/crossref_metadata_2025 huggingface dataset:
Lagrangian wall shear stress structures and near-wall transport in high-Schmidt-number aneurysmal flows
Authors: Arzani Amirhossein , Gambaruto Alberto M. , Chen Guoning , Shadden Shawn C.
Published: February 2016

The wall shear stress (WSS) vector field provides a signature for near-wall convective transport, and can be scaled to obtain a first-order approximation of the near-wall fluid velocity. The near-wall flow field governs mass transfer problems in convection-dominated open flows with high Schmidt number, in which case a flux at the wall will lead to a thin concentration boundary layer. Such near-wall transport is of particular interest in cardiovascular flows whereby haemodynamics can initiate and progress biological events at the vessel wall. In this study we consider mass transfer processes in pulsatile blood flow of abdominal aortic aneurysms resulting from complex WSS patterns. Specifically, the Lagrangian surface transport of a species released at the vessel wall was advected in forward and backward time based on the near-wall velocity field. Exposure time and residence time measures were defined to quantify accumulation of trajectories, as well as the time required to escape the near-wall domain. The effect of diffusion and normal velocity was investigated. The trajectories induced by the WSS vector field were observed to form attracting and repelling coherent structures that delineated species distribution inside the boundary layer consistent with exposure and residence time measures. The results indicate that Lagrangian WSS structures can provide a template for near-wall transport.
Axisymmetric outflows from binary point-source systems in the presence of an interface
Authors: Forbes Lawrence K.
Published: February 2016

Fluid outflow is considered, from a binary system of two point sources. The sources inject fluid of a lower density than the surrounding medium, and there is a sharp interface separating the two fluids. The overall geometry is taken to be axisymmetric around the line joining the two sources. Numerical solutions are presented for the shape of the interface in unsteady flow, and compared with a linearized solution based on small deformation of the interface from its initial spherical configuration. In addition, a novel spectral method is developed for the solution of the Boussinesq viscous flow problem, accounting exactly for the presence of the two sources and modelling the interface as a narrow region in which fluid mixing is possible. Bipolar outflow jets are seen to be possible.
Factors Associated with the Adoption of Tobacco Cessation Programmes in Schools
Authors: Little Melissa A. , Pokhrel Pallav , Sussman Steve , Derefinko Karen J. , Bursac Zoran , Rohrbach Louise Ann
Published: February 2016

Background: Although there are now a number of evidence-based tobacco use cessation programs available for dissemination, almost all adolescent tobacco cessation research comprises efficacy and effectiveness studies. As a result, there is a need for more research to guide the scaling up of these programs.

Methods: The current study utilized data from a cross-sectional sample of 205 administrators and tobacco prevention program coordinators in school districts and county offices of education throughout California, to explore factors that affect the adoption of tobacco cessation programs in schools.

Results: We found that several characteristics of the community, organization and individual respondent were associated with the adoption of evidence-based tobacco cessation programs in schools, including identifying tobacco use prevention as a community priority, having school-level SUP coordinators, greater coordinator effort devoted to tobacco use prevention, having a program champion, and currently receiving TUPE funds (all ps < .05).

Conclusions: Although the availability of dedicated tobacco education funds is an important factor in schools adopting tobacco cessation programs with proven effectiveness, our results suggest that strengthening education agencies' capacity to implement prevention programming, through dedicated resources and personnel, has the potential to lead to increased adoption of tobacco cessation programs.
Who Gets the Credit? Legislative Responsiveness and Evaluations of Members, Parties, and the US Congress
Authors: Butler Daniel M. , Karpowitz Christopher F. , Pope Jeremy C.
Published: February 2016

This article considers the hypothesis that the positive actions taken by members of Congress (MCs) influence citizens’ evaluations of them, their party, and Congress as an institution. We begin with a look at the available cross-sectional survey data on contact with legislators and legislator and institutional approval. Their legislative responsiveness appears to have a small spillover effect on institutions. However, when we employ a unique panel design that controls for prior levels of opinion and avoids recall bias, we find no evidence of spillover effects. Overall, we find that constituents who received a response from their own MC evaluate that representative more positively than those who did not receive a response, but legislator responsiveness does not predict evaluations of the MC’s political party or the Congress.
Comparison of the protective effects of intratympanic dexamethasone and methylprednisolone against cisplatin-induced ototoxicity
Authors: Özel H E , Özdoğan F , Gürgen S G , Esen E , Genç S , Selçuk A
Published: February 2016

Objective:

This study aimed to compare the efficacies of intratympanic dexamethasone and methylprednisolone in preventing in cisplatin-induced ototoxicity in rats.

Methods:

Experimental groups of rats (n = 8 each) received intratympanic isotonic saline, intraperitoneal cisplatin and intratympanic isotonic saline, intraperitoneal cisplatin and intratympanic dexamethasone, or intraperitoneal cisplatin and intratympanic methylprednisolone. Distortion product otoacoustic emission thresholds were compared on days 0 and 10 in all rats, and correlations between drug effects and changes in cochlear histology were evaluated.

Results:

Distortion product otoacoustic emission thresholds were comparable in groups III and IV (p > 0.05). Significant protection against cisplatin-induced ototoxicity was seen in groups III and IV compared with group II (p < 0.05). Dexamethasone and, to a lesser extent, methylprednisolone protected against cellular apoptosis in cisplatin-induced ototoxicity.

Conclusion:

Dexamethasone (and possibly methylprednisolone) may be clinically useful as an intratympanic chemopreventive agent to treat cisplatin ototoxicity. Future clinical studies should investigate the use of dexamethasone for this purpose in adult patients.
New oral anticoagulants – a guide for ENT surgeons
Authors: Kumar S , Moorthy R
Published: February 2016

Background:

New oral anticoagulants have been developed to overcome the perceived disadvantages of more traditional anticoagulants such as heparin and warfarin, and their use amongst ENT patients have been increasing.

Objectives:

This review article aims to discuss the mechanism of action of new oral anticoagulants, when they should be used and a protocol for their use, in both the bleeding patient and in the peri-operative setting.

Conclusion:

It is important that ENT surgeons are aware of the use of new oral anticoagulants, and have a departmental- and trust-based policy on their use and reversal in bleeding and surgical patients.
Assessing the impact of a nurse-delivered home dried blood spot service on uptake of testing for household contacts of hepatitis B-infected pregnant women across two London trusts
Authors: KEEL P. , EDWARDS G. , FLOOD J. , NIXON G. , BEEBEEJAUN K. , SHUTE J. , POH J. , MILLAR A. , IJAZ S. , PARRY J. , MANDAL S. , RAMSAY M. , AMIRTHALINGAM G.
Published: February 2016

Despite national guidance recommending testing and vaccination of household contacts of hepatitis B-infected pregnant women, provision and uptake of this is sub-optimal. The aim of this study was to evaluate the use of in-home dried blood spot (DBS) testing to increase testing and vaccination of household contacts of hepatitis B-infected pregnant women as an alternative approach to conventional primary-care follow-up. The study was conducted across two London maternity trusts (North Middlesex and Newham). All hepatitis B surface antigen-positive pregnant women identified through these trusts were eligible for inclusion. The intervention of in-home DBS testing for household contacts was introduced at North Middlesex Trust from November 2010 to December 2011. Data on testing and vaccination uptake from GP records across the two trusts were compared between baseline (2009) and intervention (2010–2011) periods. In-home DBS service increased testing uptake for all ages (P < 0·001) with the biggest impact seen in partners, where testing increased from 30·3% during the baseline period to 96·6% during the intervention period in North Middlesex Trust. Although impact on vaccine uptake was less marked, improvements were observed for adults. The provision of nurse-led home-based DBS may be useful in areas of high prevalence.
The impact of the giant iceberg B09B on population size and breeding success of Adélie penguins in Commonwealth Bay, Antarctica
Authors: Wilson Kerry-Jayne , Turney Chris S.M. , Fogwill Christopher J. , Blair Estelle
Published: February 2016

The arrival of iceberg B09B in Commonwealth Bay, East Antarctica, and subsequent fast ice expansion has dramatically increased the distance Adélie penguins (Pygoscelis adeliae) breeding at Cape Denison must travel in search of food. This has provided a natural experiment to investigate the impact of iceberg stranding events and sea ice expansion along the East Antarctic coast. As part of the Australasian Antarctic Expedition 2013–14, the Adélie penguin colony at Cape Denison was censused to compare to historic counts. Whilst some 5520 pairs still bred at Cape Denison there has been an order of magnitude decline in Adélie numbers in the area in comparison to the first counts a century ago and, critically, recent estimates based on satellite images and a census in 1997. In contrast, an Adélie population on the eastern fringe of Commonwealth Bay just 8 km from the fast ice edge was thriving, indicating the arrival of B09B and fast ice expansion was probably responsible for the observed recent population decline. In conclusion, the Cape Denison population could be extirpated within 20 years unless B09B relocates or the now perennial fast ice within the bay breaks out. Our results have important implications for wider East Antarctic if the current increasing sea ice trend continues.
SAMUEL IBN TIBBON AS THE AUTHOR OF MELAḴAH QEṬANAH, THE HEBREW TRANSLATION FROM ARABIC OF GALEN'S TEGNI: PROBES INTO THE EVOLUTION OF HIS PHILOSOPHICAL TERMINOLOGY
Authors: Freudenthal Gad
Published: February 2016

Samuel Ibn Tibbon (d. c. 1231) is best known as the translator of Maimonides's Guide of the Perplexed and as the author of the bold and ambitious cosmogonic work of Avicennian inspiration Ma'amar Yiqqawu ha-mayim (A treatise on ‘Let the water gather’; 1231). His authorship (in 1199) of the Arabic-into-Hebrew translation of Galen's Tegni with Ibn Riḍwān's commentary, known as al-Ṣināʿa al-ṣaġīra (= Small Art), is attested by the colophons of two manuscripts, but has recently been denied. The question is not unimportant, because if Ibn Tibbon indeed is the author of this translation then, as Steinschneider observed, ʿAlī Ibn Riḍwān's commentary is the first Arabic-into-Hebrew translation of a work by a Muslim writer. In this article I invalidate the arguments against Ibn Tibbon's authorship of the translation and, on the contrary, I positively show that a systematic consideration of the evidence unambiguously confirms it. The inquiry is notably based on probes into the evolution of Ibn Tibbon's philosophical vocabulary, whose results, it is hoped, will be useful beyond the immediate aim that has triggered them. This article accompanies Gad Freudenthal and Resianne Fontaine, “Philosophy and medicine in Jewish Provence, Anno 1199: Samuel Ibn Tibbon and Doeg the Edomite translating Galen's Tegni,” published in this issue of ASP, 26 (2016), pp. 1–26.
EXISTENTIAL IMPORT IN AVICENNA'S MODAL LOGIC
Authors: Chatti Saloua
Published: February 2016

In this paper, I raise the following problem: what propositions have an import in Avicenna's modal logic? Which ones do not? Starting from the assumption that the singular and quantified propositions have an import if they require the existence of their subject's referent(s) to be true, I first discuss the import of the absolute propositions then I analyze the import of the modal propositions by considering Avicenna's definitions and the relations between these propositions. This leads to the following results: Avicenna's general opinion is that the affirmatives, be they assertoric or modal, have an import while the negatives do not. The possible affirmative propositions are given an import both in the externalist and the internalist post-Avicennan readings, provided that the subject is not impossible. However, the theory is not always clear, for the propositions containing ‘sometimes not’ are given an import, together with the negative necessaries containing ‘as long as it is P’, despite their negative character; the necessary affirmative propositions containing ‘as long as it is P’ are given an import, although they do not require it. In addition, Avicenna's analysis of the special assertorics E and O (containing the internal conditions ‘at some times but not always’) and their contradictories is erroneous, which does not help determine their import. But when correctly analyzed, these special E and O do not have an import, while their contradictories – I and A special assertorics respectively – have an import.
Research and Evaluations of the Health Aspects of Disasters, Part VI: Interventional Research and the Disaster Logic Model
Authors: Birnbaum Marvin L. , Daily Elaine K. , O’Rourke Ann P. , Kushner Jennifer
Published: February 2016

Disaster-related interventions are actions or responses undertaken during any phase of a disaster to change the current status of an affected community or a Societal System. Interventional disaster research aims to evaluate the results of such interventions in order to develop standards and best practices in Disaster Health that can be applied to disaster risk reduction. Considering interventions as production functions (transformation processes) structures the analyses and cataloguing of interventions/responses that are implemented prior to, during, or following a disaster or other emergency. Since currently it is not possible to do randomized, controlled studies of disasters, in order to validate the derived standards and best practices, the results of the studies must be compared and synthesized with results from other studies (ie, systematic reviews). Such reviews will be facilitated by the selected studies being structured using accepted frameworks. A logic model is a graphic representation of the transformation processes of a program [project] that shows the intended relationships between investments and results. Logic models are used to describe a program and its theory of change, and they provide a method for the analyzing and evaluating interventions. The Disaster Logic Model (DLM) is an adaptation of a logic model used for the evaluation of educational programs and provides the structure required for the analysis of disaster-related interventions. It incorporates a(n): definition of the current functional status of a community or Societal System, identification of needs, definition of goals, selection of objectives, implementation of the intervention(s), and evaluation of the effects, outcomes, costs, and impacts of the interventions. It is useful for determining the value of an intervention and it also provides the structure for analyzing the processes used in providing the intervention according to the Relief/Recovery and Risk-Reduction Frameworks.

BirnbaumML, DailyEK, O’RourkeAP, KushnerJ. Research and evaluations of the health aspects of disasters, part VI: interventional research and the Disaster Logic Model. Prehosp Disaster Med. 2016;31(2):181–194.
Can foreign aid free the press?
Authors: DUTTA NABAMITA , WILLIAMSON CLAUDIA R.
Published: February 2016

Can foreign aid help free the press? Aid may boost press freedom by incentivizing government to reduce media regulations and provide financial support for infrastructure. Alternatively, foreign aid may prevent press freedom by expanding the role of the state and promoting government over private enterprises. We contend that the magnitude of foreign aid's influence is conditional on the existence of democratic checks. Using panel data from 1994 to 2010, we find evidence suggesting that aid significantly increases press freedom in democracies but insignificantly relates to press freedom in autocracies. Collectively, the results suggest that a standard deviation increase in aid to a country at the mean level of democracy increases press freedom by approximately a 1/20th standard deviation. Overall, the findings suggest that donors should be cautious as most aid recipients are not democratic and aid leads to only relatively small marginal improvements in press freedom.
Successful Treatment of Suicidal Risk
Authors: Schembari Blaire C. , Jobes David A. , Horgan Ryan J.
Published: February 2016

Abstract. Background: In this article we focused on analyzing surveyed patient-generated responses based on two outcome questions derived from a suicide-specific framework called the Collaborative Assessment and Management of Suicidality (CAMS): Q1 – "Were there any aspects of your treatment that were particularly helpful to you? If so, please describe these. Be as specific as possible." Q2 – "What have you learned from your clinical care that could help you if you became suicidal in the future?" Aims: To develop a reliable coding system based on formerly suicidal patients' responses to two open-ended prompts and examine most frequently identified themes. Method: The present study utilized a consensual qualitative research process to examine responses of clinically resolved suicidal patients, based on the CAMS resolution criteria (i.e., three consecutive CAMS sessions reporting the effective management of suicidal risk), to two Suicide Status Form (SSF) outcome questions (n = 49 for Q1, and n = 52 for Q2). Results: Reliable coding systems were developed and used to determine major themes of successful patient responses. Conclusion: The results of this study provide insight into patients' experiences of a successful treatment for suicidal risk with larger implications for suicide-specific treatments in general.
MYPLAN – A Mobile Phone Application for Supporting People at Risk of Suicide
Authors: Skovgaard Larsen Jette L. , Frandsen Hanne , Erlangsen Annette
Published: February 2016

Abstract. Background: Safety plans have been suggested as an intervention for people at risk of suicide. Given the impulsive character of suicidal ideation, a safety plan in the format of a mobile phone application is likely to be more available and useful than traditional paper versions. Aims: The study describes MYPLAN, a mobile phone application designed to support people at risk of suicide by letting them create a safety plan. Method: MYPLAN was developed in collaboration with clinical psychiatric staff at Danish suicide preventive clinics. The mobile application lets the user create an individualized safety plan by filling in templates with strategies, actions, and direct links to contact persons. Results: MYPLAN was developed in 2013 and is freely available in Denmark and Norway. It is designed for iPhone and android platforms. As of December 2015, the application has been downloaded almost 8,000 times. Users at risk of suicide as well as clinical staff have provided positive feedback on the mobile application. Conclusion: Support via mobile phone applications might be particularly useful for younger age groups at risk of suicide as well as in areas or countries where support options are lacking. Yet, it is important to examine the effectiveness of this type of intervention.
Global biogeography of Prochlorococcus genome diversity in the surface ocean
Authors: Kent Alyssa G , Dupont Chris L , Yooseph Shibu , Martiny Adam C
Published: February 2016

Prochlorococcus, the smallest known photosynthetic bacterium, is abundant in the ocean’s surface layer despite large variation in environmental conditions. There are several genetically divergent lineages within Prochlorococcus and superimposed on this phylogenetic diversity is extensive gene gain and loss. The environmental role in shaping the global ocean distribution of genome diversity in Prochlorococcus is largely unknown, particularly in a framework that considers the vertical and lateral mechanisms of evolution. Here we show that Prochlorococcus field populations from a global circumnavigation harbor extensive genome diversity across the surface ocean, but this diversity is not randomly distributed. We observed a significant correspondence between phylogenetic and gene content diversity, including regional differences in both phylogenetic composition and gene content that were related to environmental factors. Several gene families were strongly associated with specific regions and environmental factors, including the identification of a set of genes related to lower nutrient and temperature regions. Metagenomic assemblies of natural Prochlorococcus genomes reinforced this association by providing linkage of genes across genomic backbones. Overall, our results show that the phylogeography in Prochlorococcus taxonomy is echoed in its genome content. Thus environmental variation shapes the functional capabilities and associated ecosystem role of the globally abundant Prochlorococcus.
Genome assembly and geospatial phylogenomics of the bed bug Cimex lectularius
Authors: Rosenfeld Jeffrey A. , Reeves Darryl , Brugler Mercer R. , Narechania Apurva , Simon Sabrina , Durrett Russell , Foox Jonathan , Shianna Kevin , Schatz Michael C. , Gandara Jorge , Afshinnekoo Ebrahim , Lam Ernest T. , Hastie Alex R. , Chan Saki , Cao Han , Saghbini Michael , Kentsis Alex , Planet Paul J. , Kholodovych Vladyslav , Tessler Michael , Baker Richard , DeSalle Rob , Sorkin Louis N. , Kolokotronis Sergios-Orestis , Siddall Mark E. , Amato George , Mason Christopher E.
Published: February 2016

The common bed bug (Cimex lectularius) has been a persistent pest of humans for thousands of years, yet the genetic basis of the bed bug’s basic biology and adaptation to dense human environments is largely unknown. Here we report the assembly, annotation and phylogenetic mapping of the 697.9-Mb Cimex lectularius genome, with an N50 of 971 kb, using both long and short read technologies. A RNA-seq time course across all five developmental stages and male and female adults generated 36,985 coding and noncoding gene models. The most pronounced change in gene expression during the life cycle occurs after feeding on human blood and included genes from the Wolbachia endosymbiont, which shows a simultaneous and coordinated host/commensal response to haematophagous activity. These data provide a rich genetic resource for mapping activity and density of C. lectularius across human hosts and cities, which can help track, manage and control bed bug infestations.
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
Authors: Benoit Joshua B. , Adelman Zach N. , Reinhardt Klaus , Dolan Amanda , Poelchau Monica , Jennings Emily C. , Szuter Elise M. , Hagan Richard W. , Gujar Hemant , Shukla Jayendra Nath , Zhu Fang , Mohan M. , Nelson David R. , Rosendale Andrew J. , Derst Christian , Resnik Valentina , Wernig Sebastian , Menegazzi Pamela , Wegener Christian , Peschel Nicolai , Hendershot Jacob M. , Blenau Wolfgang , Predel Reinhard , Johnston Paul R. , Ioannidis Panagiotis , Waterhouse Robert M. , Nauen Ralf , Schorn Corinna , Ott Mark-Christoph , Maiwald Frank , Johnston J. Spencer , Gondhalekar Ameya D. , Scharf Michael E. , Peterson Brittany F. , Raje Kapil R. , Hottel Benjamin A. , Armisén David , Crumière Antonin Jean Johan , Refki Peter Nagui , Santos Maria Emilia , Sghaier Essia , Viala Sèverine , Khila Abderrahman , Ahn Seung-Joon , Childers Christopher , Lee Chien-Yueh , Lin Han , Hughes Daniel S. T. , Duncan Elizabeth J. , Murali Shwetha C. , Qu Jiaxin , Dugan Shannon , Lee Sandra L. , Chao Hsu , Dinh Huyen , Han Yi , Doddapaneni Harshavardhan , Worley Kim C. , Muzny Donna M. , Wheeler David , Panfilio Kristen A. , Vargas Jentzsch Iris M. , Vargo Edward L. , Booth Warren , Friedrich Markus , Weirauch Matthew T. , Anderson Michelle A. E. , Jones Jeffery W. , Mittapalli Omprakash , Zhao Chaoyang , Zhou Jing-Jiang , Evans Jay D. , Attardo Geoffrey M. , Robertson Hugh M. , Zdobnov Evgeny M. , Ribeiro Jose M. C. , Gibbs Richard A. , Werren John H. , Palli Subba R. , Schal Coby , Richards Stephen
Published: February 2016

The bed bug,Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of theC. lectulariussequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success ofC. lectulariusas a human ectoparasite.
Molecular sled is an eleven-amino acid vehicle facilitating biochemical interactions via sliding components along DNA
Authors: Mangel Walter F. , McGrath William J. , Xiong Kan , Graziano Vito , Blainey Paul C.
Published: February 2016

Recently, we showed the adenovirus proteinase interacts productively with its protein substrates in vitro and in vivo in nascent virus particles via one-dimensional diffusion along the viral DNA. The mechanism by which this occurs has heretofore been unknown. We show sliding of these proteins along DNA occurs on a new vehicle in molecular biology, a ‘molecular sled’ named pVIc. This 11-amino acid viral peptide binds to DNA independent of sequence. pVIc slides on DNA, exhibiting the fastest one-dimensional diffusion constant, 26±1.8 × 106 (bp)2 s−1. pVIc is a ‘molecular sled,’ because it can slide heterologous cargos along DNA, for example, a streptavidin tetramer. Similar peptides, for example, from the C terminus of β-actin or NLSIII of the p53 protein, slide along DNA. Characteristics of the ‘molecular sled’ in its milieu (virion, nucleus) have implications for how proteins in the nucleus of cells interact and imply a new form of biochemistry, one-dimensional biochemistry.
Sequential domain assembly of ribosomal protein S3 drives 40S subunit maturation
Authors: Mitterer Valentin , Murat Guillaume , Réty Stéphane , Blaud Magali , Delbos Lila , Stanborough Tamsyn , Bergler Helmut , Leulliot Nicolas , Kressler Dieter , Pertschy Brigitte
Published: February 2016

Eukaryotic ribosomes assemble by association of ribosomal RNA with ribosomal proteins into nuclear precursor particles, which undergo a complex maturation pathway coordinated by non-ribosomal assembly factors. Here, we provide functional insights into how successive structural re-arrangements in ribosomal protein S3 promote maturation of the 40S ribosomal subunit. We show that S3 dimerizes and is imported into the nucleus with its N-domain in a rotated conformation and associated with the chaperone Yar1. Initial assembly of S3 with 40S precursors occurs via its C-domain, while the N-domain protrudes from the 40S surface. Yar1 is replaced by the assembly factor Ltv1, thereby fixing the S3 N-domain in the rotated orientation and preventing its 40S association. Finally, Ltv1 release, triggered by phosphorylation, and flipping of the S3 N-domain into its final position results in the stable integration of S3. Such a stepwise assembly may represent a new paradigm for the incorporation of ribosomal proteins.
Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis
Authors: Dubin Krista , Callahan Margaret K. , Ren Boyu , Khanin Raya , Viale Agnes , Ling Lilan , No Daniel , Gobourne Asia , Littmann Eric , Huttenhower Curtis , Pamer Eric G. , Wolchok Jedd D.
Published: February 2016

The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota’s composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy.
GWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person
Authors: Hu Youna , Shmygelska Alena , Tran David , Eriksson Nicholas , Tung Joyce Y. , Hinds David A.
Published: February 2016

Circadian rhythms are a nearly universal feature of living organisms and affect almost every biological process. Our innate preference for mornings or evenings is determined by the phase of our circadian rhythms. We conduct a genome-wide association analysis of self-reported morningness, followed by analyses of biological pathways and related phenotypes. We identify 15 significantly associated loci, including seven near established circadian genes (rs12736689 near RGS16, P=7.0 × 10−18; rs9479402 near VIP, P=3.9 × 10−11; rs55694368 near PER2, P=2.6 × 10−9; rs35833281 near HCRTR2, P=3.7 × 10−9; rs11545787 near RASD1, P=1.4 × 10−8; rs11121022 near PER3, P=2.0 × 10−8; rs9565309 near FBXL3, P=3.5 × 10−8. Circadian and phototransduction pathways are enriched in our results. Morningness is associated with insomnia and other sleep phenotypes; and is associated with body mass index and depression but we did not find evidence for a causal relationship in our Mendelian randomization analysis. Our findings reinforce current understanding of circadian biology and will guide future studies.
Joint mouse–human phenome-wide association to test gene function and disease risk
Authors: Wang Xusheng , Pandey Ashutosh K. , Mulligan Megan K. , Williams Evan G. , Mozhui Khyobeni , Li Zhengsheng , Jovaisaite Virginija , Quarles L. Darryl , Xiao Zhousheng , Huang Jinsong , Capra John A. , Chen Zugen , Taylor William L. , Bastarache Lisa , Niu Xinnan , Pollard Katherine S. , Ciobanu Daniel C. , Reznik Alexander O. , Tishkov Artem V. , Zhulin Igor B. , Peng Junmin , Nelson Stanley F. , Denny Joshua C. , Auwerx Johan , Lu Lu , Williams Robert W.
Published: February 2016

Phenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for ∼5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open-access phenome consisting of ∼4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets—by far the largest coherent phenome for any experimental cohort (www.genenetwork.org). We tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human.
Ravens attribute visual access to unseen competitors
Authors: Bugnyar Thomas , Reber Stephan A. , Buckner Cameron
Published: February 2016

Recent studies purported to demonstrate that chimpanzees, monkeys and corvids possess a basic Theory of Mind, the ability to attribute mental states like seeing to others. However, these studies remain controversial because they share a common confound: the conspecific’s line of gaze, which could serve as an associative cue. Here, we show that ravens Corvus corax take into account the visual access of others, even when they cannot see a conspecific. Specifically, we find that ravens guard their caches against discovery in response to the sounds of conspecifics when a peephole is open but not when it is closed. Our results suggest that ravens can generalize from their own perceptual experience to infer the possibility of being seen. These findings confirm and unite previous work, providing strong evidence that ravens are more than mere behaviour-readers.
Topological nodal-line fermions in spin-orbit metal PbTaSe2
Authors: Bian Guang , Chang Tay-Rong , Sankar Raman , Xu Su-Yang , Zheng Hao , Neupert Titus , Chiu Ching-Kai , Huang Shin-Ming , Chang Guoqing , Belopolski Ilya , Sanchez Daniel S. , Neupane Madhab , Alidoust Nasser , Liu Chang , Wang BaoKai , Lee Chi-Cheng , Jeng Horng-Tay , Zhang Chenglong , Yuan Zhujun , Jia Shuang , Bansil Arun , Chou Fangcheng , Lin Hsin , Hasan M. Zahid
Published: February 2016

Topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems.
Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum
Authors: Lu Ake T. , Hannon Eilis , Levine Morgan E. , Hao Ke , Crimmins Eileen M. , Lunnon Katie , Kozlenkov Alexey , Mill Jonathan , Dracheva Stella , Horvath Steve
Published: February 2016

DNA methylation (DNAm) levels lend themselves for defining an epigenetic biomarker of aging known as the ‘epigenetic clock’. Our genome-wide association study (GWAS) of cerebellar epigenetic age acceleration identifies five significant (P<5.0 × 10−8) SNPs in two loci: 2p22.1 (inside gene DHX57) and 16p13.3 near gene MLST8 (a subunit of mTOR complex 1 and 2). We find that the SNP in 16p13.3 has a cis-acting effect on the expression levels of MLST8 (P=6.9 × 10−18) in most brain regions. In cerebellar samples, the SNP in 2p22.1 has a cis-effect on DHX57 (P=4.4 × 10−5). Gene sets found by our GWAS analysis of cerebellar age acceleration exhibit significant overlap with those of Alzheimer’s disease (P=4.4 × 10−15), age-related macular degeneration (P=6.4 × 10−6), and Parkinson’s disease (P=2.6 × 10−4). Overall, our results demonstrate the utility of a new paradigm for understanding aging and age-related diseases: it will be fruitful to use epigenetic tissue age as endophenotype in GWAS.
Evidence that ubiquitylated H2B corrals hDot1L on the nucleosomal surface to induce H3K79 methylation
Authors: Zhou Linjiao , Holt Matthew T. , Ohashi Nami , Zhao Aishan , Müller Manuel M. , Wang Boyuan , Muir Tom W.
Published: February 2016

Ubiquitylation of histone H2B at lysine 120 (H2B-Ub), a post-translational modification first discovered in 1980, plays a critical role in diverse nuclear processes including the regulation of transcription and DNA damage repair. Herein, we use a suite of protein chemistry methods to explore how H2B-Ub stimulates hDot1L-mediated methylation of histone H3 on lysine 79 (H3K79me). By using semisynthetic ‘designer’ chromatin containing H2B-Ub bearing a site-specifically installed photocrosslinker, here we report an interaction between a functional hotspot on ubiquitin and the N-terminus of histone H2A. Our biochemical studies indicate that this interaction is required for stimulation of hDot1L activity and leads to a repositioning of hDot1L on the nucleosomal surface, which likely places the active site of the enzyme proximal to H3K79. Collectively, our data converge on a possible mechanism for hDot1L stimulation in which H2B-Ub physically ‘corrals’ the enzyme into a productive binding orientation.
Exceptional damage-tolerance of a medium-entropy alloy CrCoNi at cryogenic temperatures
Authors: Gludovatz Bernd , Hohenwarter Anton , Thurston Keli V. S. , Bei Hongbin , Wu Zhenggang , George Easo P. , Ritchie Robert O.
Published: February 2016

High-entropy alloys are an intriguing new class of metallic materials that derive their properties from being multi-element systems that can crystallize as a single phase, despite containing high concentrations of five or more elements with different crystal structures. Here we examine an equiatomic medium-entropy alloy containing only three elements, CrCoNi, as a single-phase face-centred cubic solid solution, which displays strength-toughness properties that exceed those of all high-entropy alloys and most multi-phase alloys. At room temperature, the alloy shows tensile strengths of almost 1 GPa, failure strains of ∼70% and KJIc fracture-toughness values above 200 MPa m1/2; at cryogenic temperatures strength, ductility and toughness of the CrCoNi alloy improve to strength levels above 1.3 GPa, failure strains up to 90% and KJIc values of 275 MPa m1/2. Such properties appear to result from continuous steady strain hardening, which acts to suppress plastic instability, resulting from pronounced dislocation activity and deformation-induced nano-twinning.
DNA methylation profiling of primary neuroblastoma tumors using methyl-CpG-binding domain sequencing
Authors: Decock Anneleen , Ongenaert Maté , Van Criekinge Wim , Speleman Frank , Vandesompele Jo
Published: February 2016

Comprehensive genome-wide DNA methylation studies in neuroblastoma (NB), a childhood tumor that originates from precursor cells of the sympathetic nervous system, are scarce. Recently, we profiled the DNA methylome of 102 well-annotated primary NB tumors by methyl-CpG-binding domain (MBD) sequencing, in order to identify prognostic biomarker candidates. In this data descriptor, we give details on how this data set was generated and which bioinformatics analyses were applied during data processing. Through a series of technical validations, we illustrate that the data are of high quality and that the sequenced fragments represent methylated genomic regions. Furthermore, genes previously described to be methylated in NB are confirmed. As such, these MBD sequencing data are a valuable resource to further study the association of NB risk factors with the NB methylome, and offer the opportunity to integrate methylome data with other -omic data sets on the same tumor samples such as gene copy number and gene expression, also publically available.
Krypton oxides under pressure
Authors: Zaleski-Ejgierd Patryk , Lata Pawel M.
Published: February 2016

Under high pressure, krypton, one of the most inert elements is predicted to become sufficiently reactive to form a new class of krypton compounds; krypton oxides. Using modern ab-initio evolutionary algorithms in combination with Density Functional Theory, we predict the existence of several thermodynamically stable Kr/O species at elevated pressures. In particular, our calculations indicate that at approx. 300 GPa the monoxide, KrO, should form spontaneously and remain thermo- and dynamically stable with respect to constituent elements and higher oxides. The monoxide is predicted to form non-molecular crystals with short Kr-O contacts, typical for genuine chemical bonds.
Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential
Authors: Xu Tengfei , Fan Zheng , Li Wenxin , Dietel Barbara , Wu Yingliang , Beckmann Matthias W. , Wrosch Jana K. , Buchfelder Michael , Eyupoglu Ilker Y. , Cao Zhijian , Savaskan Nicolai E.
Published: February 2016

Brain tumors are fast proliferating and destructive within the brain microenvironment. Effective chemotherapeutic strategies are currently lacking which combat this deadly disease curatively. The glioma-specific chloride ion channel represents a specific target for therapy. Chlorotoxin (CTX), a peptide derived from scorpion venom, has been shown to be specific and efficacious in blocking glioma Cl− channel activity. Here, we report on two new derivatives (termed CA4 and CTX-23) designed and generated on the basis of the peptide sequence alignments of CTX and BmKCT. The novel peptides CA4 and CTX-23 are both effective in reducing glioma cell proliferation. In addition, CTX, CA4 and CTX-23 impact on cell migration and spheroid migration. These effects are accompanied by diminished cell extensions and increased nuclear sizes. Furthermore, we found that CA4 and CTX-23 are selective with low toxicity against primary neurons and astrocytes. In the ex vivo VOGiM, which maintain the entire brain tumor microenvironment, both CTX and CA4 display anti-tumor activity and reduce tumor volume. Hence, CTX and CA4 reveal anti-angiogenic properties with endothelial and angiogenic hotspots disrupting activities. These data report on the identification of two novel CTX derivatives with multiple anti-glioma properties including anti-angiogenesis.
Deciphering the Receptor Repertoire Encoding Specific Odorants by Time-Lapse Single-Cell Array Cytometry
Authors: Suzuki Masato , Yoshimoto Nobuo , Shimono Ken , Kuroda Shun’ichi
Published: February 2016

Mammals can recognize a vast number of odorants by using olfactory receptors (ORs) known as G protein-coupled receptors. The OR gene family is one of the most diverse gene families in mammalian genomes. Because of the vast combinations of ORs and odorants, few ORs have thus far been linked to specific odorants. Here, we established a functional screening method for OR genes by using a microchamber array containing >5,400 single olfactory epithelium-derived cells from mice applied to time-lapse single-cell array cytometry. This method facilitated the prompt isolation of single olfactory sensory neurons (OSNs) responding to the odorant of interest. Subsequent single-cell RT-PCR allowed us to isolate the genes encoding respective ORs. By using volatile molecules recognized as biomarkers for lung cancers, this method could deorphanize ORs and thereby reconstitute the OR-mediated signaling cascade in HEK293T cells. Thus, our system could be applied to identify any receptor by using specific ligands in the fields of physiopathology and pharmacology.
Gene expression and proteomic analysis of shoot apical meristem transition from dormancy to activation in Cunninghamia lanceolata (Lamb.) Hook
Authors: Xu Huimin , Cao Dechang , Chen Yanmei , Wei Dongmei , Wang Yanwei , Stevenson Rebecca Ann , Zhu Yingfang , Lin Jinxing
Published: February 2016

In contrast to annual plants, in perennial plants, the shoot apical meristem (SAM) can undergo seasonal transitions between dormancy and activity; understanding this transition is crucial for understanding growth in perennial plants. However, little is known about the molecular mechanisms of SAM development in trees. Here, light and transmission electron microscopy revealed that evident changes in starch granules, lipid bodies and cell walls thickness of the SAM in C. lanceolata during the transition from dormancy to activation. HPLC-ESI-MS/MS analysis showed that levels of indole-3-acetic acid (IAA) increased and levels of abscisic acid (ABA) decreased from dormant to active stage. Examination of 20 genes and 132 differentially expressed proteins revealed that the expression of genes and proteins potentially involved in cell division and expansion significantly increased in the active stage, whereas those related to the abscisic acid insensitive 3(ABI3), the cytoskeleton and energy metabolism decreased in the dormant stage. These findings provide new insights into the complex mechanism of gene and protein expression and their relation to cytological and physiological changes of SAM in this coniferous species.
Dielectric singularity in hyperbolic metamaterials: the inversion point of coexisting anisotropies
Authors: Caligiuri V. , Dhama R. , Sreekanth K. V. , Strangi G. , De Luca A.
Published: February 2016

Hyperbolic Metamaterials are artificially engineered materials whose optical properties can be specifically tailored to manifest an extremely high level of anisotropy. Due to this remarkable anisotropy they represent a unique opportunity to realize effective bulk meta-structure with extraordinary optical properties in the visible range. A simultaneous dielectric singularity in the in plane permittivity, with respect to the propagation direction, has to lead to a complete sign inversion of the same permittivity for that specific visible frequency. Such a drastic phase change has been theoretically highlighted in the past as the major challenge to be overcome in order to unlock many remarkable optical properties not present artificial optical systems. In this paper we experimentally demonstrate the realization of a metal-dielectric multilayer structure showing an inversion point of coexisting anisotropies at a specified wavelength in the visible range, rising from the particular design and fabrication process. Theoretical models and numerical simulations are in very good agreement with experimental data. Ellipsometrical experiments and optical modeling demonstrate the drastic type I/type II transition. Supercollimation effect has been achieved at the inversion point of the coexisting extreme anisotropies, whereas at the epsilon near zero and pole frequency the perfect lens behavior has been observed.