bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors associated withCampylobacterdetected by PCR in humans and animals in rural Cambodia
Authors: OSBJER K. , BOQVIST S. , SOKERYA S. , CHHENG K. , SAN S. , DAVUN H. , RAUTELIN H. , MAGNUSSON U.
Published: June 2016

Campylobacterare worldwide-occurring zoonotic bacteria, with the speciesCampylobacter jejuniandC. colicommonly associated with diarrhoea in children in low-income countries. In this cross-sectional study, the prevalence ofC. jejuniandC. coliin human and livestock faecal samples was detected by PCR and zoonotic risk factors associated with humanCampylobacterpositivity were identified. In total 681 humans and 753 livestock (chickens, ducks, pigs, cattle) from 269 households were sampled. Children aged <16 years were more frequentlyCampylobacterpositive (19%) than adults (8%) and multilevel logistic models revealed that humanC. jejunipositivity was associated with the following household practices: home-slaughtering [odds ratio (OR) 2·4,P= 0·01], allowing animals access to sleeping and food preparation areas (OR 2·8,P= 0·02), and eating undercooked meat (OR 6·6,P= 0·05), while frequent consumption of beef was protective (OR 0·9,P= 0·05). Associations were stronger for home-slaughtering (OR 4·9,P= 0·004) withC. jejuniinfection in children only.Campylobacterwas highly prevalent in pigs (72%) and chickens (56%) and risk factors associated with humanCampylobacterpositivity were identified throughout the meat production chain. The findings underline the importance of studying source attributions throughout the production chain and the need for upgraded understanding ofCampylobacterepidemiology in low-income countries.
Properties of domain representations of spaces through dyadic subbases
Authors: TSUKAMOTO YASUYUKI , TSUIKI HIDEKI
Published: June 2016

A dyadic subbase S of a topological space X is a subbase consisting of a countable collection of pairs of open subsets that are exteriors of each other. If a dyadic subbase S is proper, then we can construct a dcpo DS in which X is embedded. We study properties of S with respect to two aspects. (i) Whether the dcpo DS is consistently complete depends on not only S itself but also the enumeration of S. We give a characterization of S that induces the consistent completeness of DS regardless of its enumeration. (ii) If the space X is regular Hausdorff, then X is embedded in the minimal limit set of DS. We construct an example of a Hausdorff but non-regular space with a dyadic subbase S such that the minimal limit set of DS is empty.
Steering Europe: Explaining the Rise of the European Council, 1975–1986
Authors: MOURLON-DRUOL EMMANUEL
Published: June 2016

This article seeks to explain the emergence of the European Council at the heart of Europe's governance between 1975 and 1986. It highlights four factors that quickly made the newly-created institution both indispensable and stable, despite concerns over the excessive reliance on the intergovernmental method in European cooperation processes. These factors were the rise of globalisation in its multi-faceted policy dimensions, a satisfactory new-found institutional balance, the public impact of societal actors’ connections with regular and frequent heads of government meetings and the democratic legitimacy issue in European integration. The article further argues that this period witnessed the de facto emergence of the three-pillar Maastricht structure and shows how the study of the early days of the European Economic Community can shed light on the current development of the European Union and the European Council after the 2009 Lisbon Treaty.
Legume consumption and its association with fasting glucose, insulin resistance and type 2 diabetes in the Indian Migration Study
Authors: Dhillon Preet K , Bowen Liza , Kinra Sanjay , Bharathi Ankalmadugu Venkatsubbareddy , Agrawal Sutapa , Prabhakaran Dorairaj , Reddy Kolli Srinath , Ebrahim Shah ,   for the Indian Migration Study Group
Published: June 2016

Objective

Legume consumption is associated with lower fasting glucose (FG) and insulin levels in nutrition trials and lower CVD mortality in large-scale epidemiological studies. In India, legumes are widely consumed in various preparations, yet no epidemiological study has evaluated the association of legumes with FG levels, insulin resistance and diabetes risk. The present study aimed to fill this gap.

Design

Fasting blood samples, in-person interviews to obtain information on demographic/socio-economic factors, physical activity, alcohol and tobacco use, and anthropometric measurements were collected. Dietary intakes were assessed by an interviewer-administered, validated, semi-quantitative FFQ.

Setting

Lucknow, Nagpur, Hyderabad and Bangalore, India.

Subjects

Men and women (n 6367) aged 15–76 years – urban residents, urban migrants and their rural siblings.

Results

In multivariate random-effects models adjusted for age, BMI, total energy intake, macronutrients, physical activity and rural/migration status, daily legume consumption was not associated with FG (P-for-trend=0·78), insulin resistance (homeostasis model assessment score; P-for-trend=0·73) or the prevalence of type 2 diabetes mellitus (P-for-trend=0·41). Stratified analyses by vegetarian diet and migration status did not change the findings. Inverse associations between legumes and FG emerged for participants with lower BMI and higher carbohydrate, protein, fat and sugar intakes.

Conclusions

Although legumes are essential in traditional Indian diets, as well as in prudent and Mediterranean diets in the West, we did not find an association between legumes and markers of glycaemic control, insulin resistance or diabetes, except for subgroups based on BMI and macronutrient intake. The ubiquitous presence and complexity of legume preparations in Indian diets may contribute to these findings.
Collagen Fibril Ultrastructure in Mice Lacking Discoidin Domain Receptor 1
Authors: Tonniges Jeffrey R. , Albert Benjamin , Calomeni Edward P. , Roy Shuvro , Lee Joan , Mo Xiaokui , Cole Susan E. , Agarwal Gunjan
Published: June 2016

The quantity and quality of collagen fibrils in the extracellular matrix (ECM) have a pivotal role in dictating biological processes. Several collagen-binding proteins (CBPs) are known to modulate collagen deposition and fibril diameter. However, limited studies exist on alterations in the fibril ultrastructure by CBPs. In this study, we elucidate how the collagen receptor, discoidin domain receptor 1 (DDR1) regulates the collagen content and ultrastructure in the adventitia of DDR1 knock-out (KO) mice. DDR1 KO mice exhibit increased collagen deposition as observed using Masson’s trichrome. Collagen ultrastructure was evaluated in situ using transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Although the mean fibril diameter was not significantly different, DDR1 KO mice had a higher percentage of fibrils with larger diameter compared with their wild-type littermates. No significant differences were observed in the length of D-periods. In addition, collagen fibrils from DDR1 KO mice exhibited a small, but statistically significant, increase in the depth of the fibril D-periods. Consistent with these observations, a reduction in the depth of D-periods was observed in collagen fibrils reconstituted with recombinant DDR1-Fc. Our results elucidate how DDR1 modulates collagen fibril ultrastructure in vivo, which may have important consequences in the functional role(s) of the underlying ECM.
Taken lives matter: open justice and recognition in inquests into deaths at the hands of the state
Authors: McIntosh Sam
Published: June 2016

Lord Neuberger describes open justice as a procedural principle requiring that ‘what goes on in court and what a court decides is open to scrutiny’ (Neuberger, 2011). The prime rationale given for this principle is that it is a safety check on procedural fairness. Such a conception of open justice applies on only a superficial level in inquests into use-of-force deaths at the hands of the state. This paper examines the practice of, and rationales behind, opening up use-of-force deaths at the hands of the state to scrutiny through inquests. They suggest a primarily intrinsic rather than instrumental link between openness and inquests’ purposes, which requires a reframing of traditional conceptions of open justice in this context. It is further argued that recognition theory can provide the normative link between openness and justice in these circumstances – a link that is implicit in the term ‘open justice’ but rarely explored in inquests.
Exploring fatal facts: current issues in coronial law, policy and practice
Authors: Scott Bray Rebecca , Martin Greg
Published: June 2016

Death investigation and coronial practices have undergone significant social, political and legal scrutiny in recent years. A wave of coronial reform has occurred across jurisdictions, including in the United Kingdom (UK), Australia, Canada and New Zealand, with a concomitant focus on the adequacy of death investigation law and policy. Taking key coronial developments in the UK and Australia as its starting point, this paper explores a legal jurisdiction undergoing immense legal and policy reform to illustrate why coronial law and practice is of increasing scholarly interest. It begins by tracing the contentious landscape of UK coronial law reform, which has also resonated internationally, thereafter examining key controversies that refocused attention on the value of the jurisdiction, before discussing contemporary coronial issues including, publicity, human rights and death prevention.
Placental restriction in multi-fetal pregnancies increases spontaneous ambulatory activity during daylight hours in young adult female sheep
Authors: Kaur M. , Wooldridge A. L. , Wilkes M. J. , Pitchford W. S. , Hynd P. I. , McConell G. K. , Gatford K. L.
Published: June 2016

Intrauterine growth restriction (IUGR) has adverse effects on metabolic health and early life, whereas physical activity is protective against later development of metabolic disease. Relationships between birth weight and physical activity in humans, and effects of IUGR on voluntary activity in rodents, are mixed and few studies have measured physical activity in a free-ranging environment. We hypothesized that induced restriction of placental growth and function (PR) in sheep would decrease spontaneous ambulatory activity (SAA) in free-ranging adolescent and young adult progeny from multi-fetal pregnancies. To test this hypothesis, we used Global Positioning System watches to continuously record SAA between 1800 and 1200 h the following day, twice during a 16-day recording period, in progeny of control (CON, n=5 males, 9 females) and PR pregnancies (n=9 males, 10 females) as adolescents (30 weeks) and as young adults (43 weeks). PR reduced size at birth overall, but not in survivors included in SAA studies. In adolescents, SAA did not differ between treatments and females were more active than males overall and during the day (each P<0.001). In adults, daytime SAA was greater in PR than CON females (P=0.020), with a similar trend in males (P=0.053) and was greater in females than males (P=0.016). Adult SAA was negatively correlated with birth weight in females only. Contrary to our hypothesis, restricted placental function and small size at birth did not reduce progeny SAA. The mechanisms for increased daytime SAA in adult female PR and low birth weight sheep require further investigation.
Fruktosekonsum und das metabolische Syndrom: Assoziation oder Kausalität?
Authors: Gerber Philipp A.
Published: June 2016

Zusammenfassung. Der Konsum von Fruktose hat über die letzten Jahrzehnte deutlich zugenommen – vor allem durch das Süssen von Speisen und Getränken mit freier Fruktose oder mit gebundener Fruktose in Form von Haushaltszucker. Der Fruktosestoffwechsel unterscheidet sich grundlegend von jenem der Glukose. Assoziationsstudien der letzten Jahre haben einen Zusammenhang von Fruktosekonsum und ungünstigen Effekten auf den Metabolismus nahegelegt. Interventionsstudien konnten solche Effekte bestätigen und Erklärungsmodelle für die ungünstige Wirkungsweise von Fruktose liefern. Während es zu empfehlen ist, den Konsum von Fruktose als Süssstoff möglichst zu reduzieren, gibt es keine Grundlagen für eine Einschränkung des Obstkonsums (als natürliche Fruktosequelle).
Traces of Ancient Buried Subduction Zone Found in China
Authors: Strelich Lily
Published: June 2016

A combination of observations and modeling reveals evidence of a late Paleozoic intraoceanic subduction zone in the western Junggar region of northwest China.
Rare disruptive mutations and their contribution to the heritable risk of colorectal cancer
Authors: Chubb Daniel , Broderick Peter , Dobbins Sara E. , Frampton Matthew , Kinnersley Ben , Penegar Steven , Price Amy , Ma Yussanne P. , Sherborne Amy L. , Palles Claire , Timofeeva Maria N. , Bishop D. Timothy , Dunlop Malcolm G. , Tomlinson Ian , Houlston Richard S.
Published: June 2016

Colorectal cancer (CRC) displays a complex pattern of inheritance. It is postulated that much of the missing heritability of CRC is enshrined in high-impact rare alleles, which are mechanistically and clinically important. In this study, we assay the impact of rare germline mutations on CRC, analysing high-coverage exome sequencing data on 1,006 early-onset familial CRC cases and 1,609 healthy controls, with additional sequencing and array data on up to 5,552 cases and 6,792 controls. We identify highly penetrant rare mutations in 16% of familial CRC. Although the majority of these reside in known genes, we identify POT1, POLE2 and MRE11 as candidate CRC genes. We did not identify any coding low-frequency alleles (1–5%) with moderate effect. Our study clarifies the genetic architecture of CRC and probably discounts the existence of further major high-penetrance susceptibility genes, which individually account for >1% of the familial risk. Our results inform future study design and provide a resource for contextualizing the impact of new CRC genes.
ASC filament formation serves as a signal amplification mechanism for inflammasomes
Authors: Dick Mathias S. , Sborgi Lorenzo , Rühl Sebastian , Hiller Sebastian , Broz Petr
Published: June 2016

A hallmark of inflammasome activation is the ASC speck, a micrometre-sized structure formed by the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD), which consists of a pyrin domain (PYD) and a caspase recruitment domain (CARD). Here we show that assembly of the ASC speck involves oligomerization of ASCPYDinto filaments and cross-linking of these filaments by ASCCARD. ASC mutants with a non-functional CARD only assemble filaments but not specks, and moreover disrupt endogenous specks in primary macrophages. Systematic site-directed mutagenesis of ASCPYDis used to identify oligomerization-deficient ASC mutants and demonstrate that ASC speck formation is required for efficient processing of IL-1β, but dispensable for gasdermin-D cleavage and pyroptosis induction. Our results suggest that the oligomerization of ASC creates a multitude of potential caspase-1 activation sites, thus serving as a signal amplification mechanism for inflammasome-mediated cytokine production.
The biogeography of red snow microbiomes and their role in melting arctic glaciers
Authors: Lutz Stefanie , Anesio Alexandre M. , Raiswell Rob , Edwards Arwyn , Newton Rob J. , Gill Fiona , Benning Liane G.
Published: June 2016

The Arctic is melting at an unprecedented rate and key drivers are changes in snow and ice albedo. Here we show that red snow, a common algal habitat blooming after the onset of melting, plays a crucial role in decreasing albedo. Our data reveal that red pigmented snow algae are cosmopolitan as well as independent of location-specific geochemical and mineralogical factors. The patterns for snow algal diversity, pigmentation and, consequently albedo, are ubiquitous across the Arctic and the reduction in albedo accelerates snow melt and increases the time and area of exposed bare ice. We estimated that the overall decrease in snow albedo by red pigmented snow algal blooms over the course of one melt season can be 13%. This will invariably result in higher melt rates. We argue that such a ‘bio-albedo’ effect has to be considered in climate models.
The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels
Authors: Bavi Navid , Cortes D. Marien , Cox Charles D. , Rohde Paul R. , Liu Weihong , Deitmer Joachim W. , Bavi Omid , Strop Pavel , Hill Adam P. , Rees Douglas , Corry Ben , Perozo Eduardo , Martinac Boris
Published: June 2016

The bacterial mechanosensitive channel MscL gates in response to membrane tension as a result of mechanical force transmitted directly to the channel from the lipid bilayer. MscL represents an excellent model system to study the basic biophysical principles of mechanosensory transduction. However, understanding of the essential structural components that transduce bilayer tension into channel gating remains incomplete. Here using multiple experimental and computational approaches, we demonstrate that the amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane. We propose that this may also represent a common principle in the gating cycle of unrelated mechanosensitive ion channels, allowing the coupling of channel conformation to membrane dynamics.
Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-β signalling
Authors: Mirzamohammadi Fatemeh , Papaioannou Garyfallia , Inloes Jennifer B. , Rankin Erinn B. , Xie Huafeng , Schipani Ernestina , Orkin Stuart H. , Kobayashi Tatsuya
Published: June 2016

Polycomb repressive complex 2 (PRC2) controls maintenance and lineage determination of stem cells by suppressing genes that regulate cellular differentiation and tissue development. However, the role of PRC2 in lineage-committed somatic cells is mostly unknown. Here we show that Eed deficiency in chondrocytes causes severe kyphosis and a growth defect with decreased chondrocyte proliferation, accelerated hypertrophic differentiation and cell death with reduced Hif1a expression. Eed deficiency also causes induction of multiple signalling pathways in chondrocytes. Wnt signalling overactivation is responsible for the accelerated hypertrophic differentiation and kyphosis, whereas the overactivation of TGF-β signalling is responsible for the reduced proliferation and growth defect. Thus, our study demonstrates that PRC2 has an important regulatory role in lineage-committed tissue cells by suppressing overactivation of multiple signalling pathways.
Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus
Authors: Tang Xuhua , Zhu Yiping , Baker Stacey L. , Bowler Matthew W. , Chen Benjamin Jieming , Chen Chen , Hogg J. Robert , Goff Stephen P. , Song Haiwei
Published: June 2016

Retroviral reverse transcriptase (RT) of Moloney murine leukemia virus (MoMLV) is expressed in the form of a large Gag–Pol precursor protein by suppression of translational termination in which the maximal efficiency of stop codon read-through depends on the interaction between MoMLV RT and peptidyl release factor 1 (eRF1). Here, we report the crystal structure of MoMLV RT in complex with eRF1. The MoMLV RT interacts with the C-terminal domain of eRF1 via its RNase H domain to sterically occlude the binding of peptidyl release factor 3 (eRF3) to eRF1. Promotion of read-through by MoMLV RNase H prevents nonsense-mediated mRNA decay (NMD) of mRNAs. Comparison of our structure with that of HIV RT explains why HIV RT cannot interact with eRF1. Our results provide a mechanistic view of how MoMLV manipulates the host translation termination machinery for the synthesis of its own proteins.
The effect of umeclidinium added to inhaled corticosteroid/long-acting β2-agonist in patients with symptomatic COPD: a randomised, double-blind, parallel-group study
Authors: Sousa Ana R , Riley John H , Church Alison , Zhu Chang-Qing , Punekar Yogesh S , Fahy William A
Published: June 2016

Benefits of triple therapy with a long-acting muscarinic antagonist (LAMA), added to inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA), have been demonstrated. Limited data assessing the efficacy of the LAMA umeclidinium (UMEC) added to ICS/LABA are available. The aim of this study is to evaluate the efficacy and safety of UMEC added to ICS/LABAs in patients with moderate-to-very-severe COPD. This is a multicentre, randomised, double-blind, parallel-group study. Patients were symptomatic (modified Medical Research Council Dyspnoea Scale score ⩾2), despite receiving ICS/LABA (fluticasone propionate/salmeterol (FP/SAL, branded) 500/50 mcg, budesonide/formoterol (BD/FOR, branded) 200/6 mcg or 400/12 mcg, or other ICS/LABAs) ⩾30 days before the run-in (7±2 days). Patients were randomised 1:1 to once-daily UMEC 62.5 mcg or placebo (PBO), added to twice-daily open-label ICS/LABA for 12 weeks. Primary end point was trough forced expiratory volume in 1 s (FEV1) at Day 85; secondary end point was weighted mean (WM) 0–6 h FEV1 at Day 84; other end points included COPD Assessment Test (CAT) score and Transition Dyspnoea Index (TDI) score. Adverse events (AEs) were investigated. In the UMEC+ICS/LABA and PBO+ICS/LABA groups, 119 and 117 patients were randomised, respectively. Patients received FP/SAL (40%), BD/FOR (43%) and other ICS/LABAs (17%). UMEC+ICS/LABA resulted in significant improvements in trough FEV1 (Day 85) and in WM 0–6 h FEV1 (Day 84) versus PBO+ICS/LABA (difference: 123 and 148 ml, respectively, both P<0.001). Change from baseline for UMEC+ICS/LABA versus PBO+ICS/LABA was significantly different for CAT score at Day 84 (−1.31, P<0.05), but not for TDI score (0.40, P=0.152). AE incidence was similar with UMEC+ICS/LABA (38%) and PBO+ICS/LABA (42%). UMEC+ICS/LABA improved lung function and CAT score in patients with symptomatic COPD versus PBO+ICS/LABA (ClinicalTrials.gov NCT02257372).
Ketoacidosis at first presentation of type 1 diabetes mellitus among children: a study from Kuwait
Authors: Shaltout Azza Aly , Channanath Arshad Mohamed , Thanaraj Thangavel Alphonse , Omar Dina , Abdulrasoul Majedah , Zanaty Nabila , Almahdi Maria , Alkandari Hessa , AlAbdulrazzaq Dalia , d’Mello Linda , Mandani Fawziya , Alanezi Ayed , AlBasiry Eman , Alkhawari M.
Published: June 2016

We examined the frequency and severity of diabetic ketoacidosis (DKA) in 679 children and adolescents (0–14 years) at diagnosis of Type 1 Diabetes Mellitus (T1DM) in Kuwait. Between 1st January 2011 and 31st December 2013, all newly diagnosed children with diabetes were registered prospectively in a population-based electronic register. DKA was diagnosed using standard criteria based on the levels of venous pH and serum bicarbonate. At the time of diagnosis, mild/moderate DKA was present in 24.8% of the children, while severe DKA was present in 8.8%. Incidence of ketoacidosis was significantly higher in young children less than 2 (60.7% vs 32.4% p = <0.005) compared to children 2–14 years old and a higher proportion presented with severe DKA (21.4% vs 8.3% p = <0.05). No association was seen with gender. Significant differences were found in the incidence of DKA between Kuwaiti and non-Kuwaiti children (31.1% vs 39.8%; p < 0.05). Family history of diabetes had a protective effect on the occurrence of DKA (OR = 0.44; 95% CI = 0.27–0.71). Incidence of DKA in children at presentation of T1DM remains high at 33.6%. Prevention campaigns are needed to increase public awareness among health care providers, parents and school teachers in Kuwait.
Stiffness gradient of the beetle penis facilitates propulsion in the spiraled female spermathecal duct
Authors: Filippov Alexander E. , Matsumura Yoko , Kovalev Alexander E. , Gorb Stanislav N.
Published: June 2016

It is well known that sexual selection is the main driving force of substantial diversity of genitalia found in animals. However, how it facilitates the diversity is still largely unknown, because genital morpho/physical features and motions/functional morphology of the structures in sexual intercourse are not linked for the vast majority of organisms. Here we showed the presence of material gradient and numerically studied an effect of stiffness gradient of the beetle penis during its propulsion through the female duct. We found that stiffness gradient on the penis essentially affects its propulsion. Microscopic investigation suggests the possibility that the tip of the hyper-elongated penis is softer than the rest of it and our numerical model confirms that this type of distribution of stiffness gradient aids in faster propulsion than other types. This result indicates that previously ignored physical properties of genital materials are of crucial importance in evolutionary studies of genitalia.
Extra-pair paternity in the socially monogamous white stork (Ciconia ciconia) is fairly common and independent of local density
Authors: Turjeman Sondra Feldman , Centeno-Cuadros Alejandro , Eggers Ute , Rotics Shay , Blas Julio , Fiedler Wolfgang , Kaatz Michael , Jeltsch Florian , Wikelski Martin , Nathan Ran
Published: June 2016

Although many birds are socially monogamous, most (>75%) studied species are not strictly genetically monogamous, especially under high breeding density. We used molecular tools to reevaluate the reproductive strategy of the socially monogamous white stork (Ciconia ciconia) and examined local density effects. DNA samples of nestlings (Germany, Spain) were genotyped and assigned relationships using a two-program maximum likelihood classification. Relationships were successfully classified in 79.2% of German (n = 120) and 84.8% of Spanish (n = 59) nests. For each population respectively, 76.8% (n = 73) and 66.0% (n = 33) of nests contained only full-siblings, 10.5% (n = 10) and 18.0% (n = 9) had half-siblings (at least one nestling with a different parent), 3.2% (n = 3) and 10.0% (n = 5) had unrelated nestlings (at least two nestlings, each with different parents) and 9.5% (n = 9) and 6.0% (n = 3) had “not full-siblings” (could not differentiate between latter two cases). These deviations from strict monogamy place the white stork in the 59thpercentile for extra-pair paternity among studied bird species. Although high breeding density generally increases extra-pair paternity, we found no significant association with this species’ mating strategies. Thus although genetic monogamy is indeed prominent in the white stork, extra-pair paternity is fairly common compared to other bird species and cannot be explained by breeding density.
Quantitative Estimation of the Climatic Effects of Carbon Transferred by International Trade
Authors: Wei Ting , Dong Wenjie , Moore John , Yan Qing , Song Yi , Yang Zhiyong , Yuan Wenping , Chou Jieming , Cui Xuefeng , Yan Xiaodong , Wei Zhigang , Guo Yan , Yang Shili , Tian Di , Lin Pengfei , Yang Song , Wen Zhiping , Lin Hui , Chen Min , Feng Guolin , Jiang Yundi , Zhu Xian , Chen Juan , Wei Xin , Shi Wen , Zhang Zhiguo , Dong Juan , Li Yexin , Chen Deliang
Published: June 2016

Carbon transfer via international trade affects the spatial pattern of global carbon emissions by redistributing emissions related to production of goods and services. It has potential impacts on attribution of the responsibility of various countries for climate change and formulation of carbon-reduction policies. However, the effect of carbon transfer on climate change has not been quantified. Here, we present a quantitative estimate of climatic impacts of carbon transfer based on a simple CO2 Impulse Response Function and three Earth System Models. The results suggest that carbon transfer leads to a migration of CO2 by 0.1–3.9 ppm or 3–9% of the rise in the global atmospheric concentrations from developed countries to developing countries during 1990–2005 and potentially reduces the effectiveness of the Kyoto Protocol by up to 5.3%. However, the induced atmospheric CO2 concentration and climate changes (e.g., in temperature, ocean heat content and sea-ice) are very small and lie within observed interannual variability. Given continuous growth of transferred carbon emissions and their proportion in global total carbon emissions, the climatic effect of traded carbon is likely to become more significant in the future, highlighting the need to consider carbon transfer in future climate negotiations.
Differential responses of Trans-Resveratrol on proliferation of neural progenitor cells and aged rat hippocampal neurogenesis
Authors: Kumar Vivek , Pandey Ankita , Jahan Sadaf , Shukla Rajendra Kumar , Kumar Dipak , Srivastava Akriti , Singh Shripriya , Rajpurohit Chetan Singh , Yadav Sanjay , Khanna Vinay Kumar , Pant Aditya Bhushan
Published: June 2016

The plethora of literature has supported the potential benefits of Resveratrol (RV) as a life-extending as well as an anticancer compound. However, these two functional discrepancies resulted at different concentration ranges. Likewise, the role of Resveratrol on adult neurogenesis still remains controversial and less understood despite its well documented health benefits. To gather insight into the biological effects of RV on neurogenesis, we evaluated the possible effects of the compound on the proliferation and survival of neural progenitor cells (NPCs) in culture and in the hippocampus of aged rats. Resveratrol exerted biphasic effects on NPCs; low concentrations (10 μM) stimulated cell proliferation mediated by increased phosphorylation of extracellular signal-regulated kinases (ERKs) and p38 kinases, whereas high concentrations (>20 μM) exhibited inhibitory effects. Administration of Resveratrol (20 mg/kg body weight) to adult rats significantly increased the number of newly generated cells in the hippocampus, with upregulation of p-CREB and SIRT1 proteins implicated in neuronal survival and lifespan extension respectively. We have successfully demonstrated that Resveratrol exhibits dose dependent discrepancies and at a lower concentration can have a positive impact on the proliferation, survival of NPCs and aged rat hippocampal neurogenesis implicating its potential as a candidate for restorative therapies against age related disorders.
Fibroblasts of Machado Joseph Disease patients reveal autophagy impairment
Authors: Onofre Isabel , Mendonça Nuno , Lopes Sara , Nobre Rui , de Melo Joana Barbosa , Carreira Isabel Marques , Januário Cristina , Gonçalves António Freire , de Almeida Luis Pereira
Published: June 2016

Machado Joseph Disease (MJD) is the most frequent autosomal dominantly inherited cerebellar ataxia caused by the over-repetition of a CAG trinucleotide in theATXN3gene. This expansion translates into a polyglutamine tract within the ataxin-3 protein that confers a toxic gain-of-function to the mutant protein ataxin-3, contributing to protein misfolding and intracellular accumulation of aggregates and neuronal degeneration. Autophagy impairment has been shown to be one of the mechanisms that contribute for the MJD phenotype. Here we investigated whether this phenotype was present in patient-derived fibroblasts, a common somatic cell type used in the derivation of induced pluripotent stem cells and subsequent differentiation into neurons, forin vitrodisease modeling. We generated and studied adult dermal fibroblasts from 5 MJD patients and 4 healthy individuals and we found that early passage MJD fibroblasts exhibited autophagy impairment with an underlying mechanism of decreased autophagosome production. The overexpression of beclin-1 on MJD fibroblasts reverted partially autophagy impairment by increasing the autophagic flux but failed to increase the levels of autophagosome production. Overall, our results provide a well-characterized MJD fibroblast resource for neurodegenerative disease research and contribute for the understanding of mutant ataxin-3 biology and its molecular consequences.
Relativistic-microwave theory of ball lightning
Authors: Wu H.-C.
Published: June 2016

Ball lightning, a fireball sometimes observed during lightnings, has remained unexplained. Here we present a comprehensive theory for the phenomenon: At the tip of a lightning stroke reaching the ground, a relativistic electron bunch can be produced, which in turn excites intense microwave radiation. The latter ionizes the local air and the radiation pressure evacuates the resulting plasma, forming a spherical plasma bubble that stably traps the radiation. This mechanism is verified by particle simulations. The many known properties of ball lightning, such as the occurrence site, relation to the lightning channels, appearance in aircraft, its shape, size, sound, spark, spectrum, motion, as well as the resulting injuries and damages, are also explained. Our theory suggests that ball lighting can be created in the laboratory or triggered during thunderstorms. Our results should be useful for lightning protection and aviation safety, as well as stimulate research interest in the relativistic regime of microwave physics.
TCF7L1 Modulates Colorectal Cancer Growth by Inhibiting Expression of the Tumor-Suppressor Gene EPHB3
Authors: Murphy Matthew , Chatterjee Sujash S. , Jain Sidharth , Katari Manpreet , DasGupta Ramanuj
Published: June 2016

Dysregulation of the Wnt pathway leading to accumulation of β-catenin (CTNNB1) is a hallmark of colorectal cancer (CRC). Nuclear CTNNB1 acts as a transcriptional coactivator with TCF/LEF transcription factors, promoting expression of a broad set of target genes, some of which promote tumor growth. However, it remains poorly understood how CTNNB1 interacts with different transcription factors in different contexts to promote different outcomes. While some CTNNB1 target genes are oncogenic, others regulate differentiation. Here, we found that TCF7L1, a Wnt pathway repressor, buffers CTNNB1/TCF target gene expression to promote CRC growth. Loss of TCF7L1 impaired growth and colony formation of HCT116 CRC cells and reduced tumor growth in a mouse xenograft model. We identified a group of CTNNB1/TCF target genes that are activated in the absence of TCF7L1, including EPHB3, a marker of Paneth cell differentiation that has also been implicated as a tumor suppressor in CRC. Knockdown of EPHB3 partially restores growth and normal cell cycle progression of TCF7L1-Null cells. These findings suggest that while CTNNB1 accumulation is critical for CRC progression, activation of specific Wnt target genes in certain contexts may in fact inhibit tumor growth.
Metabolic and behavioral effects of mutant huntingtin deletion in Sim1 neurons in the BACHD mouse model of Huntington’s disease
Authors: Soylu-Kucharz Rana , Baldo Barbara , Petersén Åsa
Published: June 2016

Hypothalamic pathology, metabolic dysfunction and psychiatric symptoms are part of Huntington disease (HD), which is caused by an expanded CAG repeat in the huntingtin (HTT) gene. Inactivation of mutant HTT selectively in the hypothalamus prevents the development of metabolic dysfunction and depressive-like behavior in the BACHD mouse model. The hypothalamic paraventricular nucleus (PVN) is implicated in metabolic and emotional control, therefore we here tested whether inactivation of mutant HTT in the PVN affects metabolic and psychiatric manifestations of HD in BACHD mice. BACHD mice were crossed with mice expressing Cre-recombinase under the Sim1 promoter (Sim1-Cre) to inactivate mutant HTT in Sim1 expressing cells, i.e. the PVN of the hypothalamus. We found that inactivation of mutant HTT in Sim1 cells had a sex-specific effect on both the metabolic and the psychiatric phenotype, as these phenotypes were no longer different in male BACHD/Sim1-Cre mice compared to wild-type littermates. We also found a reduced number of GnRH neurons specifically in the anterior hypothalamus and an increased testes weight in male BACHD mice compared to wild-type littermates. Taken together, expression of mutant HTT in Sim1 cells may play a role for the development of metabolic dysfunction and depressive-like behavior in male BACHD mice.
Morphology of muscle attachment sites in the modern human hand does not reflect muscle architecture
Authors: Williams-Hatala E. M. , Hatala K. G. , Hiles S. , Rabey K. N.
Published: June 2016

Muscle attachment sites (entheses) on dry bones are regularly used by paleontologists to infer soft tissue anatomy and to reconstruct behaviors of extinct organisms. This method is commonly applied to fossil hominin hand bones to assess their abilities to participate in Paleolithic stone tool behaviors. Little is known, however, about how or even whether muscle anatomy and activity regimes influence the morphologies of their entheses, especially in the hand. Using the opponens muscles from a sample of modern humans, we tested the hypothesis that aspects of hand muscle architecture that are known to be influenced by behavior correlate with the size and shape of their associated entheses. Results show no consistent relationships between these behaviorally-influenced aspects of muscle architecture and entheseal morphology. Consequently, it is likely premature to infer patterns of behavior, such as stone tool making in fossil hominins, from these same entheses.
Evaluation of Consistency in Spheroid Invasion Assays
Authors: Cisneros Castillo Liliana R. , Oancea Andrei-Dumitru , Stüllein Christian , Régnier-Vigouroux Anne
Published: June 2016

Multicellular tumor spheroids embedded in a matrix represent invaluable tools to analyze cell invasion. Spheroid sizes and invasiveness are the main observables easily measurable to evaluate effects of biological or pharmaceutical manipulations on invasion. They largely account for these 3-D platforms variability, leading to flaws in data interpretation. No method has been established yet that characterizes this variability and guarantees a reliable use of 3-D platforms. Spheroid initial/end sizes and invasiveness were systematically analyzed and compared in spheroids of U87MG cells generated by three different methods and embedded at different times in a collagen matrix. A normality test was used to characterize size distribution. We introduced the linearity-over-yield analysis as a novel mathematical tool to assess end sizes and invasion reproducibility. We further provide a proof of concept by applying these tools to the analysis of a treatment known to be effective beforehand. We demonstrate that implementation of these statistical and mathematical tools warranted a confident quantification and interpretation of in 3-D conducted assays. We propose these tools could be incorporated in a guideline for generation and use of 3-D platforms.
Unraveling nonadiabatic ionization and Coulomb potential effect in strong-field photoelectron holography
Authors: Song Xiaohong , Lin Cheng , Sheng Zhihao , Liu Peng , Chen Zhangjin , Yang Weifeng , Hu Shilin , Lin C. D. , Chen Jing
Published: June 2016

Strong field photoelectron holography has been proposed as a means for interrogating the spatial and temporal information of electrons and ions in a dynamic system. After ionization, part of the electron wave packet may directly go to the detector (the reference wave), while another part may be driven back and scatters off the ion(the signal wave). The interference hologram of the two waves may be used to extract target information embedded in the collision process. Unlike conventional optical holography, however, propagation of the electron wave packet is affected by the Coulomb potential as well as by the laser field. In addition, electrons are emitted over the whole laser pulse duration, thus multiple interferences may occur. In this work, we used a generalized quantum-trajectory Monte Carlo method to investigate the effect of Coulomb potential and the nonadiabatic subcycle ionization on the photoelectron hologram. We showed that photoelectron hologram can be well described only when the effect of nonadiabatic ionization is accounted for and Coulomb potential can be neglected only in the tunnel ionization regime. Our results help paving the way for establishing photoelectron holography for probing spatial and dynamic properties of atoms and molecules.
Evolutionary features of thyroid cancer in patients with thyroidectomies from 2008 to 2013 in China
Authors: Liu Xiaoyun , Zhu Lijun , Wang Zhixiao , Cui Dai , Chen Huanhuan , Duan Yu , Shen Meiping , Lu Hui , Zhang Zhihong , Chen Jiawei , Alexander Erik K. , Yang Tao , Wang Xiaodong
Published: June 2016

To evaluate the characteristics of thyroid carcinoma over time, we carried out a retrospective study to illustrate the evolutionary features of thyroid carcinoma. All records of thyroidectomies from the First Affiliated Hospital of Nanjing Medical University from 2008 to 2013 were obtained focusing on pathological diagnosis, size, local lymph node metastasis (LNM) of the tumors. The thyroid cancer detection rate increased from 24.6% to 41.5% significantly (P < 0.05). Papillary thyroid carcinoma (PTC) remained to be the most common type counting 86.4% of all thyroid carcinomas. In all 1,704 PTCs, microPTC (mPTC) with maximum diameter less than or equal to 10 mm has become the dominant form taking up 56.5% of all PTCs in 2013 while only 43.1% in 2008. The mean maximum tumor size has decreased from 17.8 mm to 12.2 mm significantly (P < 0.05). However, the average age, female dominance and local LNM remained similarly in the past six years. Logistic regression test showed that the determinants for local LNM were age, gender and tumor size. mPTC has become the most common form of thyroid carcinoma detected during thyroidectomies in China while other features of thyroid carcinoma remained similarly in the recent years.
Assessing viral taxonomic composition in benthic marine ecosystems: reliability and efficiency of different bioinformatic tools for viral metagenomic analyses
Authors: Tangherlini M. , Dell’Anno A. , Zeigler Allen L. , Riccioni G. , Corinaldesi C.
Published: June 2016

In benthic deep-sea ecosystems, which represent the largest biome on Earth, viruses have a recognised key ecological role, but their diversity is still largely unknown. Identifying the taxonomic composition of viruses is crucial for understanding virus-host interactions, their role in food web functioning and evolutionary processes. Here, we compared the performance of various bioinformatic tools (BLAST, MG-RAST, NBC, VMGAP, MetaVir, VIROME) for analysing the viral taxonomic composition in simulated viromes and viral metagenomes from different benthic deep-sea ecosystems. The analyses of simulated viromes indicate that all the BLAST tools, followed by MetaVir and VMGAP, are more reliable in the affiliation of viral sequences and strains. When analysing the environmental viromes, tBLASTx, MetaVir, VMGAP and VIROME showed a similar efficiency of sequence annotation; however, MetaVir and tBLASTx identified a higher number of viral strains. These latter tools also identified a wider range of viral families than the others, providing a wider view of viral taxonomic diversity in benthic deep-sea ecosystems. Our findings highlight strengths and weaknesses of available bioinformatic tools for investigating the taxonomic diversity of viruses in benthic ecosystems in order to improve our comprehension of viral diversity in the oceans and its relationships with host diversity and ecosystem functioning.
Robustness of the far-field response of nonlocal plasmonic ensembles
Authors: Tserkezis Christos , Maack Johan R. , Liu Zhaowei , Wubs Martijn , Mortensen N. Asger
Published: June 2016

Contrary to classical predictions, the optical response of few-nm plasmonic particles depends on particle size due to effects such as nonlocality and electron spill-out. Ensembles of such nanoparticles are therefore expected to exhibit a nonclassical inhomogeneous spectral broadening due to size distribution. For a normal distribution of free-electron nanoparticles, and within the simple nonlocal hydrodynamic Drude model, both the nonlocal blueshift and the plasmon linewidth are shown to be considerably affected by ensemble averaging. Size-variance effects tend however to conceal nonlocality to a lesser extent when the homogeneous size-dependent broadening of individual nanoparticles is taken into account, either through a local size-dependent damping model or through the Generalized Nonlocal Optical Response theory. The role of ensemble averaging is further explored in realistic distributions of isolated or weakly-interacting noble-metal nanoparticles, as encountered in experiments, while an analytical expression to evaluate the importance of inhomogeneous broadening through measurable quantities is developed. Our findings are independent of the specific nonclassical theory used, thus providing important insight into a large range of experiments on nanoscale and quantum plasmonics.
pH-Selective Cytotoxicity of pHLIP-Antimicrobial Peptide Conjugates
Authors: Burns Kelly E. , McCleerey Tanner P. , Thévenin Damien
Published: June 2016

Positively charged antimicrobial peptides have become promising agents for the treatment of cancer by inducing apoptosis though their preferential binding and disruption of negatively charged membranes, such as the mitochondrial membrane. (KLAKLAK)2 is such a peptide but due to its polarity, it cannot cross the cellular membrane and therefore relies on the use of a delivery agent. For targeted delivery, previous studies have relied on cell penetrating peptides, nanoparticles or specific biomarkers. Herein, we investigated the first use of pHLIP to selectively target and directly translocate (KLAKLAK)2 into the cytoplasm of breast cancer cells, based on the acidic tumor micro-environment. With the goal of identifying a lead conjugate with optimized selective cytotoxicity towards cancer cells, we analyzed a family of (KLAKLAK)2 analogs with varying size, polarity and charge. We present a highly efficacious pHLIP conjugate that selectively induces concentration- and pH-dependent toxicity in breast cancer cells.
Multifarious topological quantum phase transitions in two-dimensional topological superconductors
Authors: Liu Xiao-Ping , Zhou Yuan , Wang Yi-Fei , Gong Chang-De
Published: June 2016

We study the two-dimensional topological superconductors of spinless fermions in a checkerboard-lattice Chern-insulator model. With the short-range p-wave superconducting pairing, multifarious topological quantum phase transitions have been found and several phases with high Chern numbers have been observed. We have established a rich phase diagram for these topological superconducting states. A finite-size checkerboard-lattice cylinder with a harmonic trap potential has been further investigated. Based upon the self-consistent numerical calculations of the Bogoliubov-de Gennes equations, various phase transitions have also been identified at different regions of the system. Multiple pairs of Majorana fermions are found to be well-separated and localized at the phase boundaries between the phases characterized by different Chern numbers.
Protolytic decomposition of n-octane on graphite at near room temperature
Authors: Kawashima Yasushi , Iwamoto Mitsumasa
Published: June 2016

Graphite basal surface is inert and decomposition of n-alkanes on the graphite surface has not been discovered. We here report the evidence of decomposition of n-octanes on highly oriented pyrolytic graphite (HOPG) surface, heat-treated up to 1200 °C under high vacuum (10−7 Pa), at near room temperatures. Using a temperature programmed desorption apparatus equipped with a quadrupole mass spectrometer showed the production of hydrogen molecules, methane and ethane, suggesting that the protonation of n-octane takes place on graphite surface at near room temperature. It is known that acidic functional groups are terminated at edges on the air-cleaved HOPG surface and they increase their acidity via reactions with water. However, it is most unlikely that they protonate n-alkanes at near room temperature such as superacids. We anticipate that superacidic protons, which can protonate n-octanes, are produced on the graphite surface through a novel reaction mechanism.