bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthy cognitive ageing in the Lothian Birth Cohort studies: marginal gains not magic bullet
Authors: Corley J. , Cox S. R. , Deary I. J.
Published: June 2017

In the face of shifting demographics and an increase in human longevity, it is important to examine carefully what is known about cognitive ageing, and to identify and promote possibly malleable lifestyle and health-related factors that might mitigate age-associated cognitive decline. The Lothian Birth Cohorts of 1921 (LBC1921,n= 550) and 1936 (LBC1936,n= 1091) are longitudinal studies of cognitive and brain ageing based in Scotland. Childhood IQ data are available for these participants, who were recruited in later life and then followed up regularly. This overview summarises some of the main LBC findings to date, illustrating the possible genetic and environmental contributions to cognitive function (level and change) and brain imaging biomarkers in later life. Key associations include genetic variation, health and fitness, psychosocial and lifestyle factors, and aspects of the brain's structure. It addresses some key methodological issues such as confounding by early-life intelligence and social factors and emphasises areas requiring further investigation. Overall, the findings that have emerged from the LBC studies highlight that there are multiple correlates of cognitive ability level in later life, many of which have small effects, that there are as yet few reliable predictors of cognitive change, and that not all of the correlates have independent additive associations. The concept of marginal gains, whereby there might be a cumulative effect of small incremental improvements across a wide range of lifestyle and health-related factors, may offer a useful way to think about and promote a multivariate recipe for healthy cognitive and brain ageing.
SPECIFICATION TESTING DRIVEN BY ORTHOGONAL SERIES FOR NONLINEAR COINTEGRATION WITH ENDOGENEITY
Authors: Dong Chaohua , Gao Jiti
Published: June 2017

This paper proposes two simple and new specification tests based on the use of an orthogonal series for a considerable class of bivariate nonlinearly cointegrated time series models with endogeneity and nonstationarity. The first test is proposed for the case where the regression function is integrable, which fills a gap in the literature, and the second test, which nests the first one, deals with regression functions in a quite large function space that is sufficient for both theoretical and practical use. As a starting point of our asymptotic theory, the first test is studied initially and then the theory is extended to the second test. Endogeneity in two general forms is allowed in the models to be tested. The finite sample performance of the tests is examined through several simulated examples. Our experience generally shows that the proposed tests are easily implementable and also have stable sizes and good power properties even when the ‘distance’ between the null hypothesis and a sequence of local alternatives is asymptotically negligible.
A Better Process, a Stronger UN Secretary-General: How Historic Change Was Forged and What Comes Next
Authors: Terlingen Yvonne
Published: June 2017

When on October 13, 2016, the General Assembly appointed by acclamation António Guterres of Portugal as the United Nations’ ninth secretary-general, there was a sense of excitement among the organization's 193 members. For once, so it seemed, they felt they had played an important role not only in choosing the secretary-general but also in appointing a man generally considered to be an outstanding candidate for a position memorably described as “the most impossible job on this earth.” The five permanent, veto-wielding members of the Security Council (Perm Five) still exercised the greatest power in the selection process, as they always had in the past. Yet the candidate chosen appears, surprisingly, not to have been the first choice of either the United States or Russia, two of the Perm Five that until then had effectively chosen the secretary-general between them in an opaque and outdated process. It is doubtful that António Guterres would have been appointed if the General Assembly had not embarked on a novel process to select him.
Shifting International Security Norms
Authors: Garcia Denise
Published: June 2017

The world is going through a crisis of the international liberal order, exemplified by a host of recent shocks: the invasion and annexation of Crimea by Russia; the transnational dimensions of conflicts such as in Syria; the United Kingdom's decision to exit the European Union; the attempted coup d’état in Turkey and its reversal toward autocracy; and the election and rise of non-universalist and illiberal governments as well as politicians who operate under the populist rubric in countries that are viewed as beacons of democracy and stability. These shocks have catalyzed two outcomes. First, the prevailing global norms that serve as the custodians of peace and security have been the subject of revived debate. Second, and relatedly, these shocks have prompted deep reflection on the role of institutions such as the European Union and the North Atlantic Treaty Organization (NATO), as well as the roles of the supposedly democratic members within those institutions.
Surges of advanced medical support associated with influenza outbreaks
Authors: KING J. C. , SCHWEINLE J. E. , HATCHETT R. J. , GAO Y. , LICHENSTEIN R. , ZHOU J.
Published: June 2017

We utilized de-identified data to evaluate increases in four outcomes during influenza outbreak periods (IOPs) including: hospitalization, intensive care unit admission, mechanical ventilation or death for adults aged 18 years or older with medically attended acute respiratory illnesses (MAARI) admitted to any of Maryland's 50 acute-care hospitals over 12 years. Weekly numbers of positive influenza tests in the Maryland area were obtained from the US Center for Disease Control and Prevention interactive website. The fewest consecutive weeks around the peak week containing at least 85% of the positive tests defined the IOP. Weekly counts of individual study outcomes were positively correlated with regional weekly counts of positive influenza tests during all the IOPs over 12 years. Also, rate ratios comparing daily occurrences of each study outcome between the IOP and non-IOP were significantly elevated. These results confirm conclusions of previous studies that influenza outbreaks are clearly associated with deaths and increased use of advanced medical resources by patients with MAARI. These data analyses suggest that increased efforts to develop more effective influenza vaccines and therapeutics should be a priority.
Is the medical treatment for arterial hypertension after primary aortic coarctation repair related to age at surgery? A retrospective cohort study
Authors: Lillitos Peter J , Nassar Mohamed S. , Tibby Shane M , Simmonds Joy , Salih Caner , Austin Conal , Anderson David , Krasemann Thomas
Published: June 2017

Background

Hypertension following primary coarctation repair affects up to a third of subjects. A number of studies suggest that future hypertension risk is reduced if primary repair is performed at a younger age.

Objectives

The objective of this study was to evaluate the risk of future medical treatment for hypertension depending on age of primary coarctation repair.

Methods

This study was carried out at a tertiary paediatric cardiology referral centre. Retrospective database evaluation of children aged <16 years undergoing primary surgical coarctation repair between October, 2005 and October, 2014 was carried out. Patients with complex heart diseases were excluded. The following age groups were considered: neonate (⩽28 days), infant (>28 days and ⩽12 months), and children (>12 months). Main outcome measure is the need for long-term anti-hypertensive medication. The risk for re-coarctation was also evaluated.

Results

A total of 87 patients were analysed: 60 neonates, 17 infants, 10 children. Among them, 6.7% neonates, 29.4% infants, and 40% children required long-term anti-hypertensive medications. Group differences were statistically significant (p=0.004). After adjustment for type of repair, the risk of long-term anti-hypertensive therapy was 4.5 (95% confidence interval 1.2–16.9, p=0.025) and 10.5 times (95% confidence interval 2.6–42.3, p=0.001) higher if primary repair was carried out in infancy and childhood, respectively, compared with neonates. Among all, 13 patients developed re-coarctation: 21.7% in the neonatal group, 5.9% in the infant group, and 20% in the child group. We could not demonstrate a significant difference between these proportions or calculate a reliable risk for developing re-coarctation.

Conclusions

Risk of medical treatment for hypertension was lowest when primary repair was carried out during the neonatal period, rising 10-fold if first operated on as a child. Knowing the likelihood of hypertension development depending on age of primary repair is useful for long-term surveillance and counselling.
Another bilingual advantage? Perception of talker-voice information
Authors: LEVI SUSANNAH V.
Published: June 2017

A bilingual advantage has been found in both cognitive and social tasks. In the current study, we examine whether there is a bilingual advantage in how children process information about who is talking (talker-voice information). Younger and older groups of monolingual and bilingual children completed the following talker-voice tasks with bilingual speakers: a discrimination task in English and German (an unfamiliar language), and a talker-voice learning task in which they learned to identify the voices of three unfamiliar speakers in English. Results revealed effects of age and bilingual status. Across the tasks, older children performed better than younger children and bilingual children performed better than monolingual children. Improved talker-voice processing by the bilingual children suggests that a bilingual advantage exists in a social aspect of speech perception, where the focus is not on processing the linguistic information in the signal, but instead on processing information about who is talking.
Incidental vocabulary learning in a natural reading context: an eye-tracking study
Authors: GODFROID ALINE , AHN JIEUN , CHOI INA , BALLARD LAURA , CUI YAQIONG , JOHNSTON SUZANNE , LEE SHINHYE , SARKAR ABDHI , YOON HYUNG-JO
Published: June 2017

This study responds to the call for more ecologically valid psycholinguistic research (Spivey & Cardon, 2015) by examining how readers incidentally acquire multifaceted vocabulary knowledge while reading a long, authentic text. Using eye tracking, we explore how the processing of unfamiliar words changes with repeated exposure and how the repeated exposure and processing affect word learning. In two sessions, native and non-native English speakers read five chapters of an authentic English novel containing Dari words. After reading, participants received a comprehension test and three surprise vocabulary tests. Growth curve modeling revealed a non-linear decrease in reading times that followed an S shaped curve. Number of exposures was the strongest predictor of vocabulary learning (form and meaning), while total reading time independently contributed to the learning of word meaning. Thus, both quantity and quality of lexical processing aid incremental vocabulary development and may reveal themselves differently in readers’ eye movement records.
Lock-free atom garbage collection for multithreaded Prolog - ERRATUM
Authors: WIELEMAKER JAN , HARRIS KERI
Published: June 2017

Algorithm 4 on page 960 of the above named article (Wielemaker and Harris 2016) is flawed. The issue is illustrated by algorithm 1 (supplementary figure 1). If a thread A detects the condition table too full is false it proceeds adding its atom to the table. If thread B detects the table is (now) too full it starts a resize. The resize allocates a new table and copies the atoms from the old to the new table. If thread A adds the new atom after the copy loop passes its location and before thread B activates the new table the insertion is considered successful, but the new atom is only in the deactivated old table.
Impacts of “Bomb” Cyclones Reach the Ocean Floor
Authors: Witman Sarah
Published: June 2017

Japanese researchers study explosive cyclones with models to simulate decades of ocean circulation data.
Ocean Currents Push Mainland Pollution to Remote Islands
Authors: Lunn Jenny
Published: June 2017

Marine protected areas, set up to conserve marine ecosystems and species, accumulate pollutants swept in from mainland shores by ocean currents.
Dental students’ concerns regarding OSPE and OSCE: a qualitative feedback for process improvement
Authors: Shahzad Ambreen , Saeed M Humza Bin , Paiker Sadia
Published: June 2017

Objectives:

Objective structured practical examination (OSPE) and objective structured clinical examination (OSCE) have become established as reliable, valid and objective methods of assessing practical and clinical skills in dental schools. This study explored the perceptions of dental undergraduates' regarding OSPE and OSCE.

Design and Setting:

Two focus groups were made; the first consisted of students who had recently undergone an OSPE, while the other group was of fresh graduates (FG) who had given an OSCE in the final examination. A trained facilitator conducted the discussion-based interview for each focus group. Both discussions were recorded via audio recorders and transcribed verbatim. The data were thereafter analysed thematically.

Results:

Findings from the study suggested that the students and FGs were generally satisfied with the OSPE and OSCE. However, they perceived that the time allocated to the stations was not well balanced, nor were the examiners trained to conduct the examination. More importantly, the FGs opined that practical skills were not adequately tested on the OSCE, and thus the curricular content was not adequately covered.

Conclusion:

The study highlights issues that may arise while conducting the OSPE and OSCE, thus informing future guidelines for conducting OSPE and OSCE.
Taming interfacial electronic properties of platinum nanoparticles on vacancy-abundant boron nitride nanosheets for enhanced catalysis
Authors: Zhu Wenshuai , Wu Zili , Foo Guo Shiou , Gao Xiang , Zhou Mingxia , Liu Bin , Veith Gabriel M. , Wu Peiwen , Browning Katie L. , Lee Ho Nyung , Li Huaming , Dai Sheng , Zhu Huiyuan
Published: June 2017

Taming interfacial electronic effects on Pt nanoparticles modulated by their concomitants has emerged as an intriguing approach to optimize Pt catalytic performance. Here, we report Pt nanoparticles assembled on vacancy-abundant hexagonal boron nitride nanosheets and their use as a model catalyst to embrace an interfacial electronic effect on Pt induced by the nanosheets with N-vacancies and B-vacancies for superior CO oxidation catalysis. Experimental results indicate that strong interaction exists between Pt and the vacancies. Bader charge analysis shows that with Pt on B-vacancies, the nanosheets serve as a Lewis acid to accept electrons from Pt, and on the contrary, when Pt sits on N-vacancies, the nanosheets act as a Lewis base for donating electrons to Pt. The overall-electronic effect demonstrates an electron-rich feature of Pt after assembling on hexagonal boron nitride nanosheets. Such an interfacial electronic effect makes Pt favour the adsorption of O2, alleviating CO poisoning and promoting the catalysis.
11% efficiency solid-state dye-sensitized solar cells with copper(II/I) hole transport materials
Authors: Cao Yiming , Saygili Yasemin , Ummadisingu Amita , Teuscher Joël , Luo Jingshan , Pellet Norman , Giordano Fabrizio , Zakeeruddin Shaik Mohammed , Moser Jacques -E. , Freitag Marina , Hagfeldt Anders , Grätzel Michael
Published: June 2017

Solid-state dye-sensitized solar cells currently suffer from issues such as inadequate nanopore filling, low conductivity and crystallization of hole-transport materials infiltrated in the mesoscopic TiO2 scaffolds, leading to low performances. Here we report a record 11% stable solid-state dye-sensitized solar cell under standard air mass 1.5 global using a hole-transport material composed of a blend of [Cu (4,4′,6,6′-tetramethyl-2,2′-bipyridine)2](bis(trifluoromethylsulfonyl)imide)2 and [Cu (4,4′,6,6′-tetramethyl-2,2′-bipyridine)2](bis(trifluoromethylsulfonyl)imide). The amorphous Cu(II/I) conductors that conduct holes by rapid hopping infiltrated in a 6.5 μm-thick mesoscopic TiO2 scaffold are crucial for achieving such high efficiency. Using time-resolved laser photolysis, we determine the time constants for electron injection from the photoexcited sensitizers Y123 into the TiO2 and regeneration of the Y123 by Cu(I) to be 25 ps and 3.2 μs, respectively. Our work will foster the development of low-cost solid-state photovoltaic based on transition metal complexes as hole conductors.
The influence of Antarctic subglacial volcanism on the global iron cycle during the Last Glacial Maximum
Authors: Frisia Silvia , Weyrich Laura S. , Hellstrom John , Borsato Andrea , Golledge Nicholas R. , Anesio Alexandre M. , Bajo Petra , Drysdale Russell N. , Augustinus Paul C. , Rivard Camille , Cooper Alan
Published: June 2017

Marine sediment records suggest that episodes of major atmospheric CO2 drawdown during the last glacial period were linked to iron (Fe) fertilization of subantarctic surface waters. The principal source of this Fe is thought to be dust transported from southern mid-latitude deserts. However, uncertainty exists over contributions to CO2 sequestration from complementary Fe sources, such as the Antarctic ice sheet, due to the difficulty of locating and interrogating suitable archives that have the potential to preserve such information. Here we present petrographic, geochemical and microbial DNA evidence preserved in precisely dated subglacial calcites from close to the East Antarctic Ice-Sheet margin, which together suggest that volcanically-induced drainage of Fe-rich waters during the Last Glacial Maximum could have reached the Southern Ocean. Our results support a significant contribution of Antarctic volcanism to subglacial transport and delivery of nutrients with implications on ocean productivity at peak glacial conditions.
Ruthenium(II)-catalysed remote C–H alkylations as a versatile platform to meta-decorated arenes
Authors: Li Jie , Korvorapun Korkit , De Sarkar Suman , Rogge Torben , Burns David J. , Warratz Svenja , Ackermann Lutz
Published: June 2017

The full control of positional selectivity is of prime importance in C–H activation technology. Chelation assistance served as the stimulus for the development of a plethora of ortho-selective arene functionalizations. In sharp contrast, meta-selective C–H functionalizations continue to be scarce, with all ruthenium-catalysed transformations currently requiring difficult to remove or modify nitrogen-containing heterocycles. Herein, we describe a unifying concept to access a wealth of meta-decorated arenes by a unique arene ligand effect in proximity-induced ruthenium(II) C–H activation catalysis. The transformative nature of our strategy is mirrored by providing a step-economical entry to a range of meta-substituted arenes, including ketones, acids, amines and phenols—key structural motifs in crop protection, material sciences, medicinal chemistry and pharmaceutical industries.
Genome-wide approach identifies a novel gene-maternal pre-pregnancy BMI interaction on preterm birth
Authors: Hong Xiumei , Hao Ke , Ji Hongkai , Peng Shouneng , Sherwood Ben , Di Narzo Antonio , Tsai Hui-Ju , Liu Xin , Burd Irina , Wang Guoying , Ji Yuelong , Caruso Deanna , Mao Guangyun , Bartell Tami R. , Zhang Zhongyang , Pearson Colleen , Heffner Linda , Cerda Sandra , Beaty Terri H. , Fallin M. Daniele , Lee-Parritz Aviva , Zuckerman Barry , Weeks Daniel E. , Wang Xiaobin
Published: June 2017

Preterm birth (PTB) contributes significantly to infant mortality and morbidity with lifelong impact. Few robust genetic factors of PTB have been identified. Such ‘missing heritability’ may be partly due to gene × environment interactions (G × E), which is largely unexplored. Here we conduct genome-wide G × E analyses of PTB in 1,733 African-American women (698 mothers of PTB; 1,035 of term birth) from the Boston Birth Cohort. We show that maternal COL24A1 variants have a significant genome-wide interaction with maternal pre-pregnancy overweight/obesity on PTB risk, with rs11161721 (PG × E=1.8 × 10−8; empirical PG × E=1.2 × 10−8) as the top hit. This interaction is replicated in African-American mothers (PG × E=0.01) from an independent cohort and in meta-analysis (PG × E=3.6 × 10−9), but is not replicated in Caucasians. In adipose tissue, rs11161721 is significantly associated with altered COL24A1 expression. Our findings may provide new insight into the aetiology of PTB and improve our ability to predict and prevent PTB.
DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity
Authors: Vanpouille-Box Claire , Alard Amandine , Aryankalayil Molykutty J. , Sarfraz Yasmeen , Diamond Julie M. , Schneider Robert J. , Inghirami Giorgio , Coleman C. Norman , Formenti Silvia C. , Demaria Sandra
Published: June 2017

Radiotherapy is under investigation for its ability to enhance responses to immunotherapy. However, the mechanisms by which radiation induces anti-tumour T cells remain unclear. We show that the DNA exonuclease Trex1 is induced by radiation doses above 12–18 Gy in different cancer cells, and attenuates their immunogenicity by degrading DNA that accumulates in the cytosol upon radiation. Cytosolic DNA stimulates secretion of interferon-β by cancer cells following activation of the DNA sensor cGAS and its downstream effector STING. Repeated irradiation at doses that do not induce Trex1 amplifies interferon-β production, resulting in recruitment and activation of Batf3-dependent dendritic cells. This effect is essential for priming of CD8+ T cells that mediate systemic tumour rejection (abscopal effect) in the context of immune checkpoint blockade. Thus, Trex1 is an upstream regulator of radiation-driven anti-tumour immunity. Trex1 induction may guide the selection of radiation dose and fractionation in patients treated with immunotherapy.
Anthropogenic climate change has altered primary productivity in Lake Superior
Authors: O’Beirne M. D. , Werne J. P. , Hecky R. E. , Johnson T. C. , Katsev S. , Reavie E. D.
Published: June 2017

Anthropogenic climate change has the potential to alter many facets of Earth’s freshwater resources, especially lacustrine ecosystems. The effects of anthropogenic changes in Lake Superior, which is Earth’s largest freshwater lake by area, are not well documented (spatially or temporally) and predicted future states in response to climate change vary. Here we show that Lake Superior experienced a slow, steady increase in production throughout the Holocene using (paleo)productivity proxies in lacustrine sediments to reconstruct past changes in primary production. Furthermore, data from the last century indicate a rapid increase in primary production, which we attribute to increasing surface water temperatures and longer seasonal stratification related to longer ice-free periods in Lake Superior due to anthropogenic climate warming. These observations demonstrate that anthropogenic effects have become a prominent influence on one of Earth’s largest, most pristine lacustrine ecosystems.
Genome-wide association study identifies multiple risk loci for renal cell carcinoma
Authors: Scelo Ghislaine , Purdue Mark P. , Brown Kevin M. , Johansson Mattias , Wang Zhaoming , Eckel-Passow Jeanette E. , Ye Yuanqing , Hofmann Jonathan N. , Choi Jiyeon , Foll Matthieu , Gaborieau Valerie , Machiela Mitchell J. , Colli Leandro M. , Li Peng , Sampson Joshua N. , Abedi-Ardekani Behnoush , Besse Celine , Blanche Helene , Boland Anne , Burdette Laurie , Chabrier Amelie , Durand Geoffroy , Le Calvez-Kelm Florence , Prokhortchouk Egor , Robinot Nivonirina , Skryabin Konstantin G. , Wozniak Magdalena B. , Yeager Meredith , Basta-Jovanovic Gordana , Dzamic Zoran , Foretova Lenka , Holcatova Ivana , Janout Vladimir , Mates Dana , Mukeriya Anush , Rascu Stefan , Zaridze David , Bencko Vladimir , Cybulski Cezary , Fabianova Eleonora , Jinga Viorel , Lissowska Jolanta , Lubinski Jan , Navratilova Marie , Rudnai Peter , Szeszenia-Dabrowska Neonila , Benhamou Simone , Cancel-Tassin Geraldine , Cussenot Olivier , Baglietto Laura , Boeing Heiner , Khaw Kay-Tee , Weiderpass Elisabete , Ljungberg Borje , Sitaram Raviprakash T. , Bruinsma Fiona , Jordan Susan J. , Severi Gianluca , Winship Ingrid , Hveem Kristian , Vatten Lars J. , Fletcher Tony , Koppova Kvetoslava , Larsson Susanna C. , Wolk Alicja , Banks Rosamonde E. , Selby Peter J. , Easton Douglas F. , Pharoah Paul , Andreotti Gabriella , Freeman Laura E. Beane , Koutros Stella , Albanes Demetrius , Männistö Satu , Weinstein Stephanie , Clark Peter E. , Edwards Todd L. , Lipworth Loren , Gapstur Susan M. , Stevens Victoria L. , Carol Hallie , Freedman Matthew L. , Pomerantz Mark M. , Cho Eunyoung , Kraft Peter , Preston Mark A. , Wilson Kathryn M. , Michael Gaziano J. , Sesso Howard D. , Black Amanda , Freedman Neal D. , Huang Wen-Yi , Anema John G. , Kahnoski Richard J. , Lane Brian R. , Noyes Sabrina L. , Petillo David , Teh Bin Tean , Peters Ulrike , White Emily , Anderson Garnet L. , Johnson Lisa , Luo Juhua , Buring Julie , Lee I-Min , Chow Wong-Ho , Moore Lee E. , Wood Christopher , Eisen Timothy , Henrion Marc , Larkin James , Barman Poulami , Leibovich Bradley C. , Choueiri Toni K. , Mark Lathrop G. , Rothman Nathaniel , Deleuze Jean-Francois , McKay James D. , Parker Alexander S. , Wu Xifeng , Houlston Richard S. , Brennan Paul , Chanock Stephen J.
Published: June 2017

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10−10), 3p22.1 (rs67311347, P=2.5 × 10−8), 3q26.2 (rs10936602, P=8.8 × 10−9), 8p21.3 (rs2241261, P=5.8 × 10−9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10−8), 11q22.3 (rs74911261, P=2.1 × 10−10) and 14q24.2 (rs4903064, P=2.2 × 10−24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia
Authors: Minici Claudia , Gounari Maria , Übelhart Rudolf , Scarfò Lydia , Dühren-von Minden Marcus , Schneider Dunja , Tasdogan Alpaslan , Alkhatib Alabbas , Agathangelidis Andreas , Ntoufa Stavroula , Chiorazzi Nicholas , Jumaa Hassan , Stamatopoulos Kostas , Ghia Paolo , Degano Massimo
Published: June 2017

Cell-autonomous B-cell receptor (BcR)-mediated signalling is a hallmark feature of the neoplastic B lymphocytes in chronic lymphocytic leukaemia (CLL). Here we elucidate the structural basis of autonomous activation of CLL B cells, showing that BcR immunoglobulins initiate intracellular signalling through homotypic interactions between epitopes that are specific for each subgroup of patients with homogeneous clinicobiological profiles. The molecular details of the BcR–BcR interactions apparently dictate the clinical course of disease, with stronger affinities and longer half-lives in indolent cases, and weaker, short-lived contacts mediating the aggressive ones. The diversity of homotypic BcR contacts leading to cell-autonomous signalling reconciles the existence of a shared pathogenic mechanism with the biological and clinical heterogeneity of CLL and offers opportunities for innovative treatment strategies.
Diversity spurs diversification in ecological communities
Authors: Calcagno Vincent , Jarne Philippe , Loreau Michel , Mouquet Nicolas , David Patrice
Published: June 2017

Diversity is a fundamental, yet threatened, property of ecological systems. The idea that diversity can itself favour diversification, in an autocatalytic process, is very appealing but remains controversial. Here, we study a generalized model of ecological communities and investigate how the level of initial diversity influences the possibility of evolutionary diversification. We show that even simple models of intra- and inter-specific ecological interactions can predict a positive effect of diversity on diversification: adaptive radiations may require a threshold number of species before kicking-off. We call this phenomenon DDAR (diversity-dependent adaptive radiations) and identify mathematically two distinct pathways connecting diversity to diversification, involving character displacement and the positive diversity-productivity relationship. Our results may explain observed delays in adaptive radiations at the macroscale and diversification patterns reported in experimental microbial communities, and shed new light on the dynamics of ecological diversity, the diversity-dependence of diversification rates, and the consequences of biodiversity loss.
Zinc-dependent regulation of zinc import and export genes by Zur
Authors: Choi Seung-Hwan , Lee Kang-Lok , Shin Jung-Ho , Cho Yoo-Bok , Cha Sun-Shin , Roe Jung-Hye
Published: June 2017

In most bacteria, zinc depletion is sensed by Zur, whereas the surplus is sensed by different regulators to achieve zinc homeostasis. Here we present evidence that zinc-bound Zur not only represses genes for zinc acquisition but also induces the zitB gene encoding a zinc exporter in Streptomyces coelicolor, a model actinobacteria. Zinc-dependent gene regulation by Zur occurs in two phases. At sub-femtomolar zinc concentrations (phase I), dimeric Zur binds to the Zur-box motif immediately upstream of the zitB promoter, resulting in low zitB expression. At the same time, Zur represses genes for zinc uptake. At micromolar zinc concentrations (phase II), oligomeric Zur binding with footprint expansion upward from the Zur box results in high zitB induction. Our findings reveal a mode of zinc-dependent gene activation that uses a single metalloregulator to control genes for both uptake and export over a wide range of zinc concentrations.
Real-time observation of cation exchange kinetics and dynamics at the muscovite-water interface
Authors: Lee Sang Soo , Fenter Paul , Nagy Kathryn L. , Sturchio Neil C.
Published: June 2017

Ion exchange at charged solid–liquid interfaces is central to a broad range of chemical and transport phenomena. Real-time observations of adsorption/desorption at the molecular-scale elucidate exchange reaction pathways. Here we report temporal variation in the distribution of Rb+ species at the muscovite (001)–water interface during exchange with Na+. Time-resolved resonant anomalous X-ray reflectivity measurements at 25 °C reveal that Rb+ desorption occurs over several tens of seconds during which thermodynamically stable inner-sphere Rb+ slowly transforms to a less stable outer-sphere Rb+. In contrast, Rb+ adsorption is about twice as fast, proceeding from Rb+ in the bulk solution to the stable inner-sphere species. The Arrhenius plot of the adsorption/desorption rate constants measured from 9 to 55 °C shows that the pre-exponential factor for desorption is significantly smaller than that for adsorption, indicating that this reduced attempt frequency of cation detachment largely explains the slow cation exchange processes at the interface.
MicroRNA-34a Encapsulated in Hyaluronic Acid Nanoparticles Induces Epigenetic Changes with Altered Mitochondrial Bioenergetics and Apoptosis in Non-Small-Cell Lung Cancer Cells
Authors: Trivedi Malav , Singh Amit , Talekar Meghna , Pawar Grishma , Shah Parin , Amiji Mansoor
Published: June 2017

Therapies targeting epigenetic changes for cancer treatment are in Phase I/II trials; however, all of these target only nuclear DNA. Emerging evidence suggests presence of methylation marks on mitochondrial DNA (mtDNA); but their contribution in cancer is unidentified. Expression of genes encoded on mtDNA are altered in cancer cells, along with increased glycolytic flux. Such glycolytic flux and elevated reactive oxygen species is supported by increased antioxidant; glutathione. MicroRNA-34a can translocate to mitochondria, mediate downstream apoptotic effects of tumor suppressor P53, and inhibit the antioxidant response element Nrf-2, resulting in depleted glutathione levels. Based on such strong rationale, we encapsulated microRNA-34a in our well-established Hyaluronic-Acid nanoparticles and delivered to cisplatin-sensitive and cisplatin-resistant A549-lung adenocarcinoma cells. Successful delivery and uptake in cells resulted in altered ATP levels, decreased glycolytic flux, Nrf-2 and glutathione levels, ultimately resulting in caspase-3 activation and apoptosis. Most important were the concurrent underlying molecular changes in epigenetic status of D-loop on the mtDNA and transcription of mtDNA-encoded genes. Although preliminary, we provide a novel therapeutic approach in form of altered mitochondrial bioenergetics and redox status of cancer cells with underlying changes in epigenetic status of mtDNA that can subsequently results in induction of cancer cell apoptosis.
Novel bioactive glass based injectable bone cement with improved osteoinductivity and its in vivo evaluation
Authors: zhu Tengjiao , Ren Huihui , Li Ailing , Liu Bingchuan , cui Caiyun , Dong Yanmei , Tian Yun , Qiu Dong
Published: June 2017

Recently, more and more attention has been paid to the development of a new generation of injectable bone cements that are bioactive, biodegradable and are able to have appropriate mechanical properties for treatment of vertebral compression fractures (VCFs). In this study, a novel PSC/CS composite cement with high content of PSC (a phytic acid-derived bioactive glass) was prepared and evaluated in both vitro and vivo. The PSC/CS cement showed excellent injectability, good resistance to disintegration, radiopacity and suitable mechanical properties. The in vitro test showed that the cement was bioactive, biocompatible and could maintain its shape sustainably, which made it possible to provide a long-term mechanical support for bone regeneration. Radiography, microcomputed tomography and histology of critical sized rabbit femoral condyle defects implanted with the cements proved the resorption and osteoinductivity of the cement. Compared with the PMMA and CSPC, there were more osteocyte and trabeculae at the Bone-Cement interface in the group PSC/CS cement. The volume of the residual bone cement suggested that PSC/CS had certain ability of degradation and the resorption rate was much lower than that of the CSPC cement. Together, the results indicated that the cement was a promising bone cement to treat the VCFs.
Multimode quantum states with single photons carrying orbital angular momentum
Authors: Song Xin-Bing , Fu Shi-Yao , Zhang Xiong , Yang Zhen-Wei , Zeng Qiang , Gao Chunqing , Zhang Xiangdong
Published: June 2017

We propose and experimentally demonstrate a scheme for generating multimode quantum states with single photons carrying orbital angular momentum (OAM). Various quantum states have been realized by superposing multiple OAM modes of single photons in two possible paths. These quantum states exhibit NOON-like “super-resolving” interference behavior for the multiple OAM modes of single photons. Compared with the NOON states using many photons, these states are not only easily prepared, but also robust to photon losses. They may find potential applications in quantum optical communication and recognizing defects or objects. The method to identify a particular kind of defect has been demonstrated both theoretically and experimentally.
Urinary metabolomics reveals the therapeutic effect of HuangQi Injections in cisplatin-induced nephrotoxic rats
Authors: Li Chang-Yin , Song Hui-Ting , Wang Xiao-Xiao , Wan Yao-Yao , Ding Xuan-Sheng , Liu Shi-Jia , Dai Guo-Liang , Liu Yue-Heng , Ju Wen-Zheng
Published: June 2017

The side effects of cisplatin (CDDP), notably nephrotoxicity, greatly limited its use in clinical chemotherapy. HuangQi Injections (HI), a commonly used preparation of the well-known Chinese herbal medicine Astragali radix, appeared to be promising treatment for nephrotoxicity without compromising the anti-tumor activity of CDDP. In this study, the urinary metabolomics approach using liquid chromatography time of flight mass spectrometry (LC-TOF/MS) was developed to assess the toxicity-attenuation effects and corresponding mechanisms of HI on CDDP-exposed rats. As a result, successive administration of HI significantly recovered the decline of body weight and downregulated the abnormal increase of serum creatinine and urea. HI partly restored the CDDP-induced alteration of metabolic profiling back into normal condition. Totally 43 toxicity-attenuation potential biomarkers were screened and tentatively identified, which were involved in important metabolic pathways such as amino acid metabolism, TCA cycle, fatty acid metabolism, vitamin B6 metabolism and purine metabolism. The results clearly revealed that HI could alleviate CDDP-induced nephrotoxicity and improve the disturbed metabolic balance induced by repeated CDDP exposure. The present study provided reliable evidence for the protective effect of HI on CDDP-induced toxicity with the multi-target pharmacological characteristics.
Interactions between the developmental and adult social environments mediate group dynamics and offspring traits in Drosophila melanogaster
Authors: Morimoto Juliano , Ponton Fleur , Tychsen Ilona , Cassar Jason , Wigby Stuart
Published: June 2017

Developmental conditions can strongly influence adult phenotypes and social interactions, which in turn affect key evolutionary processes such as sexual selection and sexual conflict. While the implications of social interactions in phenotypically mixed populations at the individual level are increasingly well known, how these effects influence the fate of groups remains poorly understood, which limits our understanding of the broader ecological implications. To address this problem we manipulated adult phenotypes and social composition inDrosophila melanogaster– by experimentally manipulating the larval density of the group-members – and measured a range of group-level outcomes across the lifespan of groups. Adult groups composed of exclusively low larval-density individuals showed high courtship levels, and low early reproductive rates, group growth rates, offspring mass and offspring eclosion success, relative to high larval-density or mixed larval-density groups. Furthermore, high larval-density groups had lower survival. Offspring mass increased with time, but at a reduced rate in groups when male group members (but not females) were from a mixture of larval-densities; peak reproductive rates were also earlier in these groups. Our results suggest that that variation in developmental conditions experienced by adult group members can modify the reproductive output of groups.
Hydrogen gas protects IP3Rs by reducing disulfide bridges in human keratinocytes under oxidative stress
Authors: Wu Ching-Ying , Hsu Wen-Li , Tsai Ming-Hsien , Liang Jui-Lin , Lu Jian-He , Yen Chia-Jung , Yu Hsin-Su , Noda Mami , Lu Chi-Yu , Chen Chu-Huang , Yan Shian-Jang , Yoshioka Tohru
Published: June 2017

Based on the oxidative stress theory, aging derives from the accumulation of oxidized proteins induced by reactive oxygen species (ROS) in the cytoplasm. Hydrogen peroxide (H2O2) elicits ROS that induces skin aging through oxidation of proteins, forming disulfide bridges with cysteine or methionine sulfhydryl groups. Decreased Ca2+ signaling is observed in aged cells, probably secondary to the formation of disulfide bonds among Ca2+ signaling-related proteins. Skin aging processes are modeled by treating keratinocytes with H2O2. In the present study, H2O2 dose-dependently impaired the adenosine triphosphate (ATP)-induced Ca2+ response, which was partially protected via co-treatment with β-mercaptoethanol, resulting in reduced disulfide bond formation in inositol 1, 4, 5-trisphosphate receptors (IP3Rs). Molecular hydrogen (H2) was found to be more effectively protected H2O2-induced IP3R1 dysfunction by reducing disulfide bonds, rather than quenching ROS. In conclusion, skin aging processes may involve ROS-induced protein dysfunction due to disulfide bond formation, and H2 can protect oxidation of this process.
c-Abl regulates gastrointestinal muscularis propria homeostasis via ERKs
Authors: Xiang Jinnan , Zhang Yiqun , Bao Dandan , Cao Na , Zhang Xin , Li Ping , Qiu Shoutao , Guo Jigang , He Dan , Li Baojie , Yao Liqing , Liu Huijuan
Published: June 2017

The gastrointestinal tract is responsible for food digestion and absorption. The muscularis propria propels the foodstuff through the GI tract and defects in intestine motility may cause obstruction disorders. Our present genetic studies identified non-receptor tyrosine kinase c-Abl as an important regulator of the muscularis propria homeostasis and a risk factor for rectal prolapse. Mouse deficient for c-Abl showed defects in the muscularis propria of gastrointestinal tract and older c-Abl−/− mice developed megaesophagus and rectal prolapse. Inhibition of c-Abl with imatinib mesylate, an anti-CML drug, or ablation of c-Abl using Prx1-Cre, which marks smooth muscle cells, recapitulated most of the muscularis propria phenotypes. The pathogenesis of rectal prolapse was attributable to overproliferation of smooth muscle cells, which was caused by enhanced ERK1/2 activation. Administration of ERK inhibitor U0126 impeded the development of rectal prolapse in c-Abl deficient mice. These results reveal a role for c-Abl-regulated smooth muscle proliferation in the pathogenesis of rectal prolapse, and imply that long-term use of imatinib mesylate may cause gastrointestinal problems in patients while ERK inhibitor may be effective in treating rectal prolapse.
Applying modern psychometric techniques to melodic discrimination testing: Item response theory, computerised adaptive testing, and automatic item generation
Authors: Harrison Peter M. C. , Collins Tom , Müllensiefen Daniel
Published: June 2017

Modern psychometric theory provides many useful tools for ability testing, such as item response theory, computerised adaptive testing, and automatic item generation. However, these techniques have yet to be integrated into mainstream psychological practice. This is unfortunate, because modern psychometric techniques can bring many benefits, including sophisticated reliability measures, improved construct validity, avoidance of exposure effects, and improved efficiency. In the present research we therefore use these techniques to develop a new test of a well-studied psychological capacity: melodic discrimination, the ability to detect differences between melodies. We calibrate and validate this test in a series of studies. Studies 1 and 2 respectively calibrate and validate an initial test version, while Studies 3 and 4 calibrate and validate an updated test version incorporating additional easy items. The results support the new test’s viability, with evidence for strong reliability and construct validity. We discuss how these modern psychometric techniques may also be profitably applied to other areas of music psychology and psychological science in general.
Design of a Peripheral Building Block for H-Bonded Dendritic Frameworks and Analysis of the Void Space in the Bulk Dendrimers
Authors: Lee Cheng-Hua , Soldatov Dmitriy V. , Tzeng Chung-Hao , Lai Long-Li , Lu Kuang-Lieh
Published: June 2017

Three dendrimers, (t-Bu-G
2
N)
2
, CC(t-Bu-G
1
N)
3
and (t-Bu-G
1
N)
2
, with 3,5-di-tert-butyl amidobenzene as a common peripheral moiety were prepared in 64–83% yields and characterized. The bulk solids had high BET surface areas of 136–138 m2/g, which were similar for the three dendrimers in spite of their different molecular weight (ranging from 1791 to 2890). It was concluded that the peripheral amide groups do not imbed in the interstitial space of neighbouring dendrimer molecules but rather build a supramolecular architecture through strong intermolecular H-bonds. This mode of assembly generates voids in the bulk dendrimers responsible for sorption properties. The X-ray crystal structure analysis of a compound representing the peripheral moiety of the dendrimers and the FT-IR and powder-XRD data for (t-Bu-G
1
N)
2
suggest the proposed supramolecular structure. The isosteric heats of CO2 sorption (Qst) for (t-Bu-G
2
N)
2
were significantly higher than those for the other two dendrimers, which is consistent with the formation of a different type of voids within the interstitial space of the molecule. It is suggested that the interstitial void space can be designed and tuned to adjust its properties to a particular task, such as the separation of gases or a catalytic reaction facilitated by the dendrimer.
Validation of optimal reference genes for quantitative real time PCR in muscle and adipose tissue for obesity and diabetes research
Authors: Perez Lester J. , Rios Liliam , Trivedi Purvi , D’Souza Kenneth , Cowie Andrew , Nzirorera Carine , Webster Duncan , Brunt Keith , Legare Jean-Francois , Hassan Ansar , Kienesberger Petra C. , Pulinilkunnil Thomas
Published: June 2017

The global incidence of obesity has led to an increasing need for understanding the molecular mechanisms that drive this epidemic and its comorbidities. Quantitative real-time RT-PCR (RT-qPCR) is the most reliable and widely used method for gene expression analysis. The selection of suitable reference genes (RGs) is critical for obtaining accurate gene expression information. The current study aimed to identify optimal RGs to perform quantitative transcriptomic analysis based on RT-qPCR for obesity and diabetes research, employing in vitro and mouse models, and human tissue samples. Using the ReFinder program we evaluated the stability of a total of 15 RGs. The impact of choosing the most suitable RGs versus less suitable RGs on RT-qPCR results was assessed. Optimal RGs differed between tissue and cell type, species, and experimental conditions. By employing different sets of RGs to normalize the mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), we show that sub-optimal RGs can markedly alter the PGC1α gene expression profile. Our study demonstrates the importance of validating RGs prior to normalizing transcriptional expression levels of target genes and identifies optimal RG pairs for reliable RT-qPCR normalization in cells and in human and murine muscle and adipose tissue for obesity/diabetes research.
Formation of Biphasic Hydroxylapatite-Beta Magnesium Tricalcium Phosphate in Heat Treated Salmonid Vertebrae
Authors: Butler Don H. , Shahack-Gross Ruth
Published: June 2017

Ichthyoarchaeological evidence is uncommon at ancient hunter-gatherer sites from various regions and timeframes. This research contributes to the development of microarchaeological techniques useful for identifying fishing economies in situations where classifiable bones are unavailable. Specifically, traces of heat altered bone mineral in domestic hearths are expected to provide markers for discarded fish remains. We used a series of laboratory incineration experiments to characterize the mineralogy of burned salmonid vertebrae. Fourier transform infrared spectroscopy and x-ray diffraction distinguished the formation of beta magnesium tricalcium phosphate (βMgTCP) at temperatures as low as 600 °C. Bones from a sample of game mammals and birds did not form this phase at temperatures below 1,000 °C. We propose that this neoformed mineral can serve as a proxy for hunter-gatherer salmonid fishing when typical ichthyoarchaeological evidence is absent. Using Fourier transform infrared spectroscopy, it will be possible to rapidly and inexpensively determine the presence of βMgTCP in fragmentary burned bone remains associated with combustion features. The occurrence of βMgTCP in archaeological hearth features will offer a new means of further evaluating the temporal, geographic, and cultural scope of salmonid harvesting. We also acknowledge the value of biphasic hydroxylapatite-βMgTCP recovered from Atlantic salmon vertebrae as a bioceramic.