bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher-order orbifold Euler characteristics for compact Lie group actions
Authors: Gusein-Zade S. M. , Luengo I. , Melle-Hernández A.
Published: November 2015

We generalize the notions of the orbifold Euler characteristic and of the higher-order orbifold Euler characteristics to spaces with actions of a compact Lie group using integration with respect to the Euler characteristic instead of the summation over finite sets. We show that the equation for the generating series of the kth-order orbifold Euler characteristics of the Cartesian products of the space with the wreath products actions proved by Tamanoi for finite group actions and by Farsi and Seaton for compact Lie group actions with finite isotropy subgroups holds in this case as well.
Environmental factors and public health policy associated with human and rodent infection by leptospirosis: a land cover-based study in Nan province, Thailand
Authors: DELLA ROSSA P. , TANTRAKARNAPA K. , SUTDAN D. , KASETSINSOMBAT K. , COSSON J.-F. , SUPPUTAMONGKOL Y. , CHAISIRI K. , TRAN A. , SUPPUTAMONGKOL S. , BINOT A. , LAJAUNIE C. , MORAND S.
Published: November 2015

Leptospirosis incidence has increased markedly since 1995 in Thailand, with the eastern and northern parts being the most affected regions, particularly during flooding events. Here, we attempt to overview the evolution of human prevalence during the past decade and identify the environmental factors that correlate with the incidence of leptospirosis and the clinical incidence in humans. We used an extensive survey of Leptospira infection in rodents conducted in 2008 and 2009 and the human incidence of the disease from 2003 to 2012 in 168 villages of two districts of Nan province in Northern Thailand. Using an ad-hoc developed land-use cover implemented in a geographical information system we showed that humans and rodents were not infected in the same environment/habitat in the land-use cover. High village prevalence was observed in open habitat near rivers for the whole decade, or in 2008–2009 mostly in rice fields prone to flooding, whereas infected rodents (2008–2009) were observed in patchy habitat with high forest cover, mostly situated on sloping ground areas. We also investigated the potential effects of public health campaigns conducted after the dramatic flood event of 2006. We showed that, before 2006, human incidence in villages was explained by the population size of the village according to the environmental source of infection of this disease, while as a result of the campaigns, human incidence in villages after 2006 appeared independent of their population size. This study confirms the role of the environment and particularly land use, in the transmission of bacteria, emphasized by the effects of the provincial public health campaigns on the epidemiological pattern of incidence, and questions the role of rodents as reservoirs.
Impact of Early Environment on Children's Mental Health: Lessons From DNA Methylation Studies With Monozygotic Twins
Authors: Chiarella Julian , Tremblay Richard E. , Szyf Moshe , Provençal Nadine , Booij Linda
Published: November 2015

Over the past decade, epigenetic analyses have made important contributions to our understanding of healthy development and a wide variety of adverse conditions such as cancer and psychopathology. There is increasing evidence that DNA methylation is a mechanism by which environmental factors influence gene transcription and, ultimately, phenotype. However, differentiating the effects of the environment from those of genetics on DNA methylation profiles remains a significant challenge. Monozygotic (MZ) twin study designs are unique in their ability to control for genetic differences because each pair of MZ twins shares essentially the same genetic sequence with the exception of a small number of de novo mutations and copy number variations. Thus, differences within twin pairs in gene expression and phenotype, including behavior, can be attributed in the majority of cases to environmental effects rather than genetic influence. In this article, we review the literature showing how MZ twin designs can be used to study basic epigenetic principles, contributing to understanding the role of early in utero and postnatal environmental factors on the development of psychopathology. We also highlight the importance of initiating longitudinal and experimental studies with MZ twins during pregnancy. This approach is especially important to identify: (1) critical time periods during which the early environment can impact brain and mental health development, and (2) the specific mechanisms through which early environmental effects may be mediated. These studies may inform the optimum timing and design for early preventive interventions aimed at reducing risk for psychopathology.
Geriatric Psychiatry in Motion – Bringing Physical Exercise to Geriatric Psychiatry
Authors: Fleiner Tim , Trost Andrea , Depiereux René , Zijlstra Wiebren , Häussermann Peter
Published: November 2015

Abstract. Although programs to promote physical activity have been implemented in routine geriatric psychiatry, there are presently no evidence-based recommendations and only few randomized controlled exercise trials have been conducted. Therefore, a program called Geriatric Psychiatry in Motion was established in a psychiatric hospital. The primary objective was to promote physical activity and to investigate the effects of different physical activity programs in elderly psychiatric patients. The following key features were developed and are under investigation: (1) a program to promote general physical activity; (2) specific exercise programs for inpatients; (3) specific programs for outpatient services; and (4) the implementation of an integrative objective mobility and physical activity assessment. The first results show benefits for patients, caregivers as well as hospital staff.
Daily Activity Abilities in MCI, Alzheimer’s Disease, and Healthy Controls
Authors: Avila Justina , Flowers Amina , Scott Travis M. , Quilici Jill , Apostolova Liana G. , Woo Ellen , Ringman John , Razani Jill
Published: November 2015

Abstract. Mild cognitive impairment (MCI) is a risk state for dementia. The present study assessed daily functioning in MCI individuals (amnestic [aMCI] and nonamnestic [naMCI]) relative to those with Alzheimer’s disease (AD) and healthy controls (NC). Twenty AD participants, 14 aMCI, 12 naMCI, and 30 healthy controls were administered the Direct Assessment of Functional Status (DAFS). The AD group performed poorer than all groups on all DAFS subscales. The aMCI group performed poorer than controls on the shopping subtests, while the naMCI group performed poorer than controls on only the free recall shopping. Finally, DAFS subscales discriminated the AD and aMCI groups well, but only recognition shopping discriminated between naMCI and aMCI individuals. These findings suggest that circumscribed ADL deficits distinguish subtypes of MCI and AD.
Forecast Versus Reality: High-Resolution Weather Prediction
Authors: Strelich Lily
Published: November 2015

Researchers test the High-Resolution Rapid Refresh model with real-life observational data to evaluate forecast accuracy.
Whole-exome and targeted sequencing identify ROBO1 and ROBO2 mutations as progression-related drivers in myelodysplastic syndromes
Authors: Xu Feng , Wu Ling-Yun , Chang Chun-Kang , He Qi , Zhang Zheng , Liu Li , Shi Wen-Hui , Guo Juan , Zhu Yang , Zhao You-Shan , Gu Shu-Cheng , Fei Cheng-Ming , Wu Dong , Zhou Li-Yu , Su Ji-Ying , Song Lu-Xi , Xiao Chao , Li Xiao
Published: November 2015

The progressive mechanism underlying myelodysplastic syndrome remains unknown. Here we identify ROBO1 and ROBO2 as novel progression-related somatic mutations using whole-exome and targeted sequencing in 6 of 16 (37.5%) paired MDS patients with disease progression. Further deep sequencing detects 20 (10.4%) patients with ROBO mutations in a cohort of 193 MDS patients. In addition, copy number loss and loss of heterogeneity (LOH) of ROBO1 and ROBO2 are frequently observed in patients with progression or carrying ROBO mutations. In in vitro experiments, overexpression of ROBO1 or ROBO2 produces anti-proliferative and pro-apoptotic effects in leukaemia cells. However, this effect was lost in ROBO mutants and ROBO-SLIT2 signalling is impaired. Multivariate analysis shows that ROBO mutations are independent factors for predicting poor survival. These findings demonstrate a novel contribution of ROBO mutations to the pathogenesis of MDS and highlight a key role for ROBO-SLIT2 signalling in MDS disease progression.
Thermodynamic controls of the Atlantic Niño
Authors: Nnamchi Hyacinth C. , Li Jianping , Kucharski Fred , Kang In-Sik , Keenlyside Noel S. , Chang Ping , Farneti Riccardo
Published: November 2015

Prevailing theories on the equatorial Atlantic Niño are based on the dynamical interaction between atmosphere and ocean. However, dynamical coupled ocean-atmosphere models poorly simulate and predict equatorial Atlantic climate variability. Here we use multi-model numerical experiments to show that thermodynamic feedbacks excited by stochastic atmospheric perturbations can generate Atlantic Niño s.d. of ∼0.28±0.07 K, explaining ∼68±23% of the observed interannual variability. Thus, in state-of-the-art coupled models, Atlantic Niño variability strongly depends on the thermodynamic component (R2=0.92). Coupled dynamics acts to improve the characteristic Niño-like spatial structure but not necessarily the variance. Perturbations of the equatorial Atlantic trade winds (∼±1.53 m s−1) can drive changes in surface latent heat flux (∼±14.35 W m−2) and thus in surface temperature consistent with a first-order autoregressive process. By challenging the dynamical paradigm of equatorial Atlantic variability, our findings suggest that the current theories on its modelling and predictability must be revised.
Rapid Holocene thinning of an East Antarctic outlet glacier driven by marine ice sheet instability
Authors: Jones R. S. , Mackintosh A. N. , Norton K. P. , Golledge N. R. , Fogwill C. J. , Kubik P. W. , Christl M. , Greenwood S. L.
Published: November 2015

Outlet glaciers grounded on a bed that deepens inland and extends below sea level are potentially vulnerable to ‘marine ice sheet instability’. This instability, which may lead to runaway ice loss, has been simulated in models, but its consequences have not been directly observed in geological records. Here we provide new surface-exposure ages from an outlet of the East Antarctic Ice Sheet that reveal rapid glacier thinning occurred approximately 7,000 years ago, in the absence of large environmental changes. Glacier thinning persisted for more than two and a half centuries, resulting in hundreds of metres of ice loss. Numerical simulations indicate that ice surface drawdown accelerated when the otherwise steadily retreating glacier encountered a bedrock trough. Together, the geological reconstruction and numerical simulations suggest that centennial-scale glacier thinning arose from unstable grounding line retreat. Capturing these instability processes in ice sheet models is important for predicting Antarctica’s future contribution to sea level change.
Adaptation to acetaminophen exposure elicits major changes in expression and distribution of the hepatic proteome
Authors: Eakins R. , Walsh J. , Randle L. , Jenkins R. E. , Schuppe-Koistinen I. , Rowe C. , Starkey Lewis P. , Vasieva O. , Prats N. , Brillant N. , Auli M. , Bayliss M. , Webb S. , Rees J. A. , Kitteringham N. R. , Goldring C. E. , Park B. K.
Published: November 2015

Acetaminophen overdose is the leading cause of acute liver failure. One dose of 10–15 g causes severe liver damage in humans, whereas repeated exposure to acetaminophen in humans and animal models results in autoprotection. Insight of this process is limited to select proteins implicated in acetaminophen toxicity and cellular defence. Here we investigate hepatic adaptation to acetaminophen toxicity from a whole proteome perspective, using quantitative mass spectrometry. In a rat model, we show the response to acetaminophen involves the expression of 30% of all proteins detected in the liver. Genetic ablation of a master regulator of cellular defence, NFE2L2, has little effect, suggesting redundancy in the regulation of adaptation. We show that adaptation to acetaminophen has a spatial component, involving a shift in regionalisation of CYP2E1, which may prevent toxicity thresholds being reached. These data reveal unexpected complexity and dynamic behaviour in the biological response to drug-induced liver injury.
Isocaloric Pair-Fed High-Carbohydrate Diet Induced More Hepatic Steatosis and Inflammation than High-Fat Diet Mediated by miR-34a/SIRT1 Axis in Mice
Authors: Li Xinli , Lian Fuzhi , Liu Chun , Hu Kang-Quan , Wang Xiang-Dong
Published: November 2015

To investigate the different effects of isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) on hepatic steatosis and the underlying mechanisms, especially the role of microRNA-34a/silent information regulator T1 (SIRT1) axis, C57BL/6J mice (n = 12/group) were isocaloric pair-fed with Lieber-DeCarli liquid diet containing either high fat (HFLD) or high carbohydrate (HCLD) for 16 weeks. As compared to the HFLD fed mice, despite the similar final body weights, HCLD feeding: (1) induced more severe hepatic steatosis; (2) up-regulated hepatic expression of miR-34a accompanied with significant decrease of SIRT1 and nicotinamide phosphoribosyltransferase (NAMPT), SIRT1 activity and phosphorylation of AMPK; (3) up-regulated de novo lipogenesis (DNL) related proteins expression (ACC, SCD1) and down-regulated expressions of miR-122, miR-370 and miR-33; (4) decreased mRNA expressions of genes Cpt1, Pparα and Pgc1α related to fatty acid oxidation; (5) increased hepatic total cholesterol concentration and decreased expression of cholesterol metabolism related genes Abcg5, Abcg8, Abcg11, Cyp7a1 and Cyp8b1; and (6) induced higher hepatic inflammatory response accompanied with significant increased mRNA expressions of Il1β, Tnfα and Mcp1. Thus, isocaloric HCLD feeding induced greater severity in hepatic steatosis and inflammatory response than HFLD feeding, potentially through miR-34a/SIRT1 axis mediated promotion of DNL, inhibition of fatty acid oxidation and cholesterol metabolism.
Cognitive requirements of cumulative culture: teaching is useful but not essential
Authors: Zwirner Elena , Thornton Alex
Published: November 2015

The cumulative nature of human culture is unique in the animal kingdom. Progressive improvements in tools and technologies have facilitated humanity’s spread across the globe and shaped human evolution, but the cognitive mechanisms enabling cultural change remain unclear. Here we show that, contrary to theoretical predictions, cumulative improvements in tools are not dependent on specialised, high-fidelity social learning mechanisms. Participants were tasked with building a basket to carry as much rice as possible using a set of everyday materials and divided into treatment groups with differing opportunities to learn asocially, imitate, receive teaching or emulate by examining baskets made by previous chain members. Teaching chains produced more robust baskets, but neither teaching nor imitation were strictly necessary for cumulative improvements; emulation chains generated equivalent increases in efficacy despite exhibiting relatively low copying fidelity. People used social information strategically, choosing different materials to make their baskets if the previous basket in the chain performed poorly. Together, these results suggest that cumulative culture does not rest on high-fidelity social learning mechanisms alone. Instead, the roots of human cultural prowess may lie in the interplay of strategic social learning with other cognitive traits including the ability to reverse engineer artefacts through causal reasoning.
High-Performance Wrap-Gated InGaAs Nanowire Field-Effect Transistors with Sputtered Dielectrics
Authors: Shen Li-Fan , Yip SenPo , Yang Zai-xing , Fang Ming , Hung TakFu , Pun Edwin Y.B. , Ho Johnny C.
Published: November 2015

Although wrap-gated nanowire field-effect-transistors (NWFETs) have been explored as an ideal electronic device geometry for low-power and high-frequency applications, further performance enhancement and practical implementation are still suffering from electron scattering on nanowire surface/interface traps between the nanowire channel and gate dielectric as well as the complicated device fabrication scheme. Here, we report the development of high-performance wrap-gated InGaAs NWFETs using conventional sputtered Al2O3 layers as gate dielectrics, instead of the typically employed atomic layer deposited counterparts. Importantly, the surface chemical passivation of NW channels performed right before the dielectric deposition is found to significantly alleviate plasma induced defect traps on the NW channel. Utilizing this passivation, the wrap-gated device exhibits superior electrical performances: a high ION/IOFF ratio of ~2 × 106, an extremely low sub-threshold slope of 80 mV/decade and a peak field-effect electron mobility of ~1600 cm2/(Vs) at VDS = 0.1 V at room temperature, in which these values are even better than the ones of state-of-the-art NWFETs reported so far. By combining sputtering and pre-deposition chemical passivation to achieve high-quality gate dielectrics for wrap-gated NWFETs, the superior gate coupling and electrical performances have been achieved, confirming the effectiveness of our hybrid approach for future advanced electronic devices.
Copper nanocoils synthesized through solvothermal method
Authors: Liu Yanjuan , Liu Xiaowei , Zhan Yongjie , Fan Haiming , Lu Yang
Published: November 2015

Recently helical nanostructures such as nanosprings and nanocoils have drawn great interests in nanotechnology, due to their unique morphologies and physical properties and they may be potential building blocks in sorts of electromechanical, magnetic, photoelectronic and plasmonic devices at micro/nanoscales. In this report, multi-turns copper nanocoils were synthesized through a modified solvothermal method, in which the mixture of water and N-methyl-2-pyrrolidone (NMP) were selected as reaction medium and copolymer poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP/VA 64E) as reductant. In the liquid solution, nanosprings could be formed from relaxed nanocoils and demonstrated high elasticity. These nanocoils and nanosprings are of single crystalline structure, with the characteristics wire diameters ranging from tens to a few hundreds of nanometers and the ring/coil diameters mostly ~10–35 microns. Their growth and deformation mechanisms were then investigated and discussed along with that of previously reported single-turn copper nanorings. This work could be of importance for researchers working on synthesis and applications of novel 1-D helical nanomaterials and their functional devices.
Exploiting a moment of weakness: male spiders escape sexual cannibalism by copulating with moulting females
Authors: Uhl Gabriele , Zimmer Stefanie M. , Renner Dirk , Schneider Jutta M.
Published: November 2015

Sexual cannibalism is a particularly extreme example of conflict between the sexes, depriving the male of future reproduction. Theory predicts that sexual conflict should induce counter-adaptations in the victim. Observations of male spiders mating with moulting and hence largely immobile females suggest that this behaviour functions to circumvent female control and cannibalism. However, we lack quantitative estimates of natural frequencies and fitness consequences of these unconventional matings. To understand the importance of mating while moulting in cannibalistic mating systems, we combined mating experiments and paternity assessment in the laboratory with extensive field observations using the sexually cannibalistic orb-web spiderArgiope bruennichi.Copulations with moulting females resulted in 97% male survival compared with only 20% in conventional matings. Mating while moulting provided similar paternity benefits compared with conventional matings. Our findings support the hypothesis that mating with moulting females evolved under sexual conflict and safely evades sexual cannibalism. Despite male benefits, natural frequencies were estimated around 44% and directly predicted by a male guarding a subadult female. Since only adult females signal their presence, the difficulty for males to locate subadult females might limit further spreading of mating with moulting females.
Parity and Risk of Stroke among Chinese Women: Cross-sectional Evidence from the Dongfeng-Tongji Cohort Study
Authors: Zhang Yanmei , Shen Lijun , Wu Jing , Xu Guiqiang , Song Lulu , Yang Siyi , Tian Yaohua , Yuan Jing , Liang Yuan , Wang Youjie
Published: November 2015

Epidemiological studies have investigated the association between parity and the risk of stroke, but the results have been inconsistent. The objective of this study was to assess the association among middle-aged and older Chinese women. We used data from the Dongfeng-Tongji Cohort Study. In total, 14,277 women were included in the analysis. Participants were classified into four groups according to parity. Stroke cases were self-reported during face-to-face interviews. Multivariable logistic regression models were used to investigate the association between parity and the risk of stroke while controlling for potential confounders. The prevalence of stroke among the study subjects was 2.7% (380 of 14,277). In the fully adjusted model, women who had experienced two, three, or four or more live births had 1.24 times (95% CI, 0.85–1.81), 1.97 times (95% CI, 1.30–2.98) and 1.86 times (95% CI, 1.14–3.03), higher risk of stroke, respectively, compared with women who had experienced one live birth. High parity was associated with an increasing risk of stroke in the present study. Further longitudinal studies are needed to confirm the association and to explore the unclear mechanism underlying the link between parity and stroke risk.
Efficient Synchronization of Dipolarly Coupled Vortex-Based Spin Transfer Nano-Oscillators
Authors: Locatelli Nicolas , Hamadeh Abbass , Abreu Araujo Flavio , Belanovsky Anatoly D. , Skirdkov Petr N. , Lebrun Romain , Naletov Vladimir V. , Zvezdin Konstantin A. , Muñoz Manuel , Grollier Julie , Klein Olivier , Cros Vincent , de Loubens Grégoire
Published: November 2015

Due to their nonlinear properties, spin transfer nano-oscillators can easily adapt their frequency to external stimuli. This makes them interesting model systems to study the effects of synchronization and brings some opportunities to improve their microwave characteristics in view of their applications in information and communication technologies and/or to design innovative computing architectures. So far, mutual synchronization of spin transfer nano-oscillators through propagating spinwaves and exchange coupling in a common magnetic layer has been demonstrated. Here we show that the dipolar interaction is also an efficient mechanism to synchronize neighbouring oscillators. We experimentally study a pair of vortex-based spin transfer nano-oscillators, in which mutual synchronization can be achieved despite a significant frequency mismatch between oscillators. Importantly, the coupling efficiency is controlled by the magnetic configuration of the vortices, as confirmed by an analytical model and micromagnetic simulations highlighting the physics at play in the synchronization process.
A unified analytic solution approach to static bending and free vibration problems of rectangular thin plates
Authors: Li Rui , Wang Pengcheng , Tian Yu , Wang Bo , Li Gang
Published: November 2015

A unified analytic solution approach to both static bending and free vibration problems of rectangular thin plates is demonstrated in this paper, with focus on the application to corner-supported plates. The solution procedure is based on a novel symplectic superposition method, which transforms the problems into the Hamiltonian system and yields accurate enough results via step-by-step rigorous derivation. The main advantage of the developed approach is its wide applicability since no trial solutions are needed in the analysis, which is completely different from the other methods. Numerical examples for both static bending and free vibration plates are presented to validate the developed analytic solutions and to offer new numerical results. The approach is expected to serve as a benchmark analytic approach due to its effectiveness and accuracy.
A rice tonoplastic calcium exchanger, OsCCX2 mediates Ca2+/cation transport in yeast
Authors: Yadav Akhilesh K. , Shankar Alka , Jha Saroj K. , Kanwar Poonam , Pandey Amita , Pandey Girdhar K.
Published: November 2015

In plant cell, cations gradient in cellular compartments is maintained by synergistic action of various exchangers, pumps and channels. The Arabidopsis exchanger family members (AtCCX3 and AtCCX5) were previously studied and belong to CaCA (calcium cation exchangers) superfamily while none of the rice CCXs has been functionally characterized for their cation transport activities till date. Rice genome encode four CCXs and only OsCCX2 transcript showed differential expression under abiotic stresses and Ca2+ starvation conditions. The OsCCX2 localized to tonoplast and suppresses the Ca2+ sensitivity of K667 (low affinity Ca2+ uptake deficient) yeast mutant under excess CaCl2 conditions. In contrast to AtCCXs, OsCCX2 expressing K667 yeast cells show tolerance towards excess Na+, Li+, Fe2+, Zn2+ and Co2+ and suggest its ability to transport both mono as well as divalent cations in yeast. Additionally, in contrast to previously characterized AtCCXs, OsCCX2 is unable to complement yeast trk1trk2 double mutant suggesting inability to transport K+ in yeast system. These finding suggest that OsCCX2 having distinct metal transport properties than previously characterized plant CCXs. OsCCX2 can be used as potential candidate for enhancing the abiotic stress tolerance in plants as well as for phytoremediation of heavy metal polluted soil.
Downregulation of the small GTPase SAR1A: a key event underlying alcohol-induced Golgi fragmentation in hepatocytes
Authors: Petrosyan Armen , Cheng Pi-Wan , Clemens Dahn L. , Casey Carol A.
Published: November 2015

The hepatic asialoglycoprotein receptor (ASGP-R) is posttranslationally modified in the Golgi en route to the plasma membrane, where it mediates clearance of desialylated serum glycoproteins. It is known that content of plasma membrane-associated ASGP-R is decreased after ethanol exposure, although the mechanisms remain elusive. Previously, we found that formation of compact Golgi requires dimerization of the largest Golgi matrix protein giantin. We hypothesize that ethanol-impaired giantin function may be related to altered trafficking of ASGP-R. Here we report that in HepG2 cells expressing alcohol dehydrogenase and hepatocytes of ethanol-fed rats, ethanol metabolism results in Golgi disorganization. This process is initiated by dysfunction of SAR1A GTPase followed by altered COPII vesicle formation and impaired Golgi delivery of the protein disulfide isomerase A3 (PDIA3), an enzyme that catalyzes giantin dimerization. Additionally, we show that SAR1A gene silencing in hepatocytes mimics the effect of ethanol: dedimerization of giantin, arresting PDIA3 in the endoplasmic reticulum (ER) and large-scale alterations in Golgi architecture. Ethanol-induced Golgi fission has no effect on ER-to-Golgi transportation of ASGP-R, however, it results in its deposition in cis-medial-, but not trans-Golgi. Thus, alcohol-induced deficiency in COPII vesicle formation predetermines Golgi fragmentation which, in turn, compromises the Golgi-to-plasma membrane transportation of ASGP-R.
Electrophysiological and Histological Characterization of Rod-Cone Retinal Degeneration and Microglia Activation in a Mouse Model of Mucopolysaccharidosis Type IIIB
Authors: Tse Dennis Y. , Lotfi Parisa , Simons David L. , Sardiello Marco , Wu Samuel M.
Published: November 2015

Sanfilippo syndrome Type B or Mucopolysaccharidosis IIIB (MPS IIIB) is a neurodegenerative autosomal recessive lysosomal storage disorder in which patients suffer severe vision loss from associated retinopathy. Here we sought to study the underlying retinal functional and morphological changes associated with MPS IIIB disease progression using the established model of MPS IIIB, the B6.129S6-Naglu(tm1Efn)/J mouse line. Electroretinogram (ERG) was recorded from MPS IIIB and wild-type (WT) mice at the age of 28 and 46 weeks and retinal tissues were subsequently collected for immunohistochemistry analysis. At the 28th week, rod a- and b-wave amplitudes were significantly diminished in MPS IIIB compared to WT mice. The cone a- and b-waves of MPS IIIB mice were not significantly different from those of the control at the 28th week but were significantly diminished at the 46th week, when MPS IIIB mice showed a major loss of rods and rod bipolar cells in both central and peripheral regions and a minor loss of cones in the periphery. Activation of microglia and neovascularization were also detected in the MPS IIIB retina. The new findings that cones and rod bipolar cells also undergo degeneration and that retinal microglia are activated, will inform future development of therapeutic strategies.
Inferring the hosts of coronavirus using dual statistical models based on nucleotide composition
Authors: Tang Qin , Song Yulong , Shi Mijuan , Cheng Yingyin , Zhang Wanting , Xia Xiao-Qin
Published: November 2015

Many coronaviruses are capable of interspecies transmission. Some of them have caused worldwide panic as emerging human pathogens in recent years, e.g., severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In order to assess their threat to humans, we explored to infer the potential hosts of coronaviruses using a dual-model approach based on nineteen parameters computed from spike genes of coronaviruses. Both the support vector machine (SVM) model and the Mahalanobis distance (MD) discriminant model achieved high accuracies in leave-one-out cross-validation of training data consisting of 730 representative coronaviruses (99.86% and 98.08% respectively). Predictions on 47 additional coronaviruses precisely conformed to conclusions or speculations by other researchers. Our approach is implemented as a web server that can be accessed at http://bioinfo.ihb.ac.cn/seq2hosts.
Nap sleep spindle correlates of intelligence
Authors: Ujma Péter P. , Bódizs Róbert , Gombos Ferenc , Stintzing Johannes , Konrad Boris N. , Genzel Lisa , Steiger Axel , Dresler Martin
Published: November 2015

Sleep spindles are thalamocortical oscillations in non-rapid eye movement (NREM) sleep, that play an important role in sleep-related neuroplasticity and offline information processing. Several studies with full-night sleep recordings have reported a positive association between sleep spindles and fluid intelligence scores, however more recently it has been shown that only few sleep spindle measures correlate with intelligence in females and none in males. Sleep spindle regulation underlies a circadian rhythm, however the association between spindles and intelligence has not been investigated in daytime nap sleep so far. In a sample of 86 healthy male human subjects, we investigated the correlation between fluid intelligence and sleep spindle parameters in an afternoon nap of 100 minutes. Mean sleep spindle length, amplitude and density were computed for each subject and for each derivation for both slow and fast spindles. A positive association was found between intelligence and slow spindle duration, but not any other sleep spindle parameter. As a positive correlation between intelligence and slow sleep spindle duration in full-night polysomnography has only been reported in females but not males, our results suggest that the association between intelligence and sleep spindles is more complex than previously assumed.
Development and evaluation of an up-converting phosphor technology-based lateral flow assay for rapid detection of Francisella tularensis
Authors: Hua Fei , Zhang Pingping , Zhang Fuli , Zhao Yong , Li Chunfeng , Sun Chongyun , Wang Xiaochen , Yang Ruifu , Wang Chengbin , Yu Ailian , Zhou Lei
Published: November 2015

Francisella tularensis is a potential biowarfare/bioterrorism agent and zoonotic pathogen that causes tularemia; thus, surveillance of F. tularensis and first-level emergency response using point-of-care testing (POCT) are essential. The UPT-LF POCT assay was established to quantitatively detect F. tularensis within 15 min and the sensitivity of the assay was 104 CFU · mL−1 (100 CFU/test). The linear quantitative range covered five orders of magnitude and the coefficients of variation were less than 10%. Except Shigella dysenteriae, UPT-LF showed excellent specificity to four strains that are also potential biowarfare/bioterrorism agents and 13 food-borne pathogenic strains. Samples with pH 2–13, high ion strengths (≥2 mol · L−1 solution of KCl and NaCl), high viscosities (≤50 mg · mL−1 PEG20000 or ≥20% glycerol) and high concentrations of biomacromolecules (≥400 mg · mL−1 bovine serum albumin or ≥80 mg · mL−1 casein) showed little influence on the assay. For practical utilization, the tolerance limits for seven powders and eight viscera were determined and operation errors of liquid measurement demonstrated a minor influence on the strip. Ftu-UPT-LF is a candidate POCT method because of its excellent sensitivity, specificity, and stability in complex samples, as well as low operation error.
Time-lapse electrical impedance spectroscopy for monitoring the cell cycle of single immobilized S. pombe cells
Authors: Zhu Zhen , Frey Olivier , Haandbaek Niels , Franke Felix , Rudolf Fabian , Hierlemann Andreas
Published: November 2015

As a complement and alternative to optical methods, wide-band electrical impedance spectroscopy (EIS) enables multi-parameter, label-free and real-time detection of cellular and subcellular features. We report on a microfluidics-based system designed to reliably capture single rod-shaped Schizosaccharomyces pombe cells by applying suction through orifices in a channel wall. The system enables subsequent culturing of immobilized cells in an upright position, while dynamic changes in cell-cycle state and morphology were continuously monitored through EIS over a broad frequency range. Besides measuring cell growth, clear impedance signals for nuclear division have been obtained. The EIS system has been characterized with respect to sensitivity and detection limits. The spatial resolution in measuring cell length was 0.25 μm, which corresponds to approximately a 5-min interval of cell growth under standard conditions. The comprehensive impedance data sets were also used to determine the occurrence of nuclear division and cytokinesis. The obtained results have been validated through concurrent confocal imaging and plausibilized through comparison with finite-element modeling data. The possibility to monitor cellular and intracellular features of single S. pombe cells during the cell cycle at high spatiotemporal resolution renders the presented microfluidics-based EIS system a suitable tool for dynamic single-cell investigations.
Matrix metalloproteinase-12 is an essential mediator of acute and chronic arterial stiffening
Authors: Liu Shu-Lin , Bae Yong Ho , Yu Christopher , Monslow James , Hawthorne Elizabeth A. , Castagnino Paola , Branchetti Emanuela , Ferrari Giovanni , Damrauer Scott M. , Puré Ellen , Assoian Richard K.
Published: November 2015

Arterial stiffening is a hallmark of aging and risk factor for cardiovascular disease, yet its regulation is poorly understood. Here we use mouse modeling to show that matrix metalloproteinase-12 (MMP12), a potent elastase, is essential for acute and chronic arterial stiffening. MMP12 was induced in arterial smooth muscle cells (SMCs) after acute vascular injury. As determined by genome-wide analysis, the magnitude of its gene induction exceeded that of all other MMPs as well as those of the fibrillar collagens and lysyl oxidases, other common regulators of tissue stiffness. A preferential induction of SMC MMP12, without comparable effect on collagen abundance or structure, was also seen during chronic arterial stiffening with age. In both settings, deletion of MMP12 reduced elastin degradation and blocked arterial stiffening as assessed by atomic force microscopy and immunostaining for stiffness-regulated molecular markers. Isolated MMP12-null SMCs sense extracellular stiffness normally, indicating that MMP12 causes arterial stiffening by remodeling the SMC microenvironment rather than affecting the mechanoresponsiveness of the cells themselves. In human aortic samples, MMP12 levels strongly correlate with markers of SMC stiffness. We conclude that MMP12 causes arterial stiffening in mice and suggest that it functions similarly in humans.
Rescue from tau-induced neuronal dysfunction produces insoluble tau oligomers
Authors: Cowan Catherine M. , Quraishe Shmma , Hands Sarah , Sealey Megan , Mahajan Sumeet , Allan Douglas W. , Mudher Amritpal
Published: November 2015

Aggregation of highly phosphorylated tau is a hallmark of Alzheimer’s disease and other tauopathies. Nevertheless, animal models demonstrate that tau-mediated dysfunction/toxicity may not require large tau aggregates but instead may be caused by soluble hyper-phosphorylated tau or by small tau oligomers. Challenging this widely held view, we use multiple techniques to show that insoluble tau oligomers form in conditions where tau-mediated dysfunction is rescued in vivo. This shows that tau oligomers are not necessarily always toxic. Furthermore, their formation correlates with increased tau levels, caused intriguingly, by either pharmacological or genetic inhibition of tau kinase glycogen-synthase-kinase-3beta (GSK-3β). Moreover, contrary to common belief, these tau oligomers were neither highly phosphorylated and nor did they contain beta-pleated sheet structure. This may explain their lack of toxicity. Our study makes the novel observation that tau also forms non-toxic insoluble oligomers in vivo in addition to toxic oligomers, which have been reported by others. Whether these are inert or actively protective remains to be established. Nevertheless, this has wide implications for emerging therapeutic strategies such as those that target dissolution of tau oligomers as they may be ineffective or even counterproductive unless they act on the relevant toxic oligomeric tau species.
Nucleoside phosphorylation by the mineral schreibersite
Authors: Gull Maheen , Mojica Mike A. , Fernández Facundo M. , Gaul David A. , Orlando Thomas M. , Liotta Charles L. , Pasek Matthew A.
Published: November 2015

Phosphorylation of the nucleosides adenosine and uridine by the simple mixing and mild heating of aqueous solutions of the organic compounds with synthetic analogs of the meteoritic mineral schreibersite, (Fe,Ni)3P under slightly basic conditions (pH ~9) is reported. These results suggest a potential role for meteoritic phosphorus in the origin and development of early life.
Harpin Hpa1 Interacts with Aquaporin PIP1;4 to Promote the Substrate Transport and Photosynthesis in Arabidopsis
Authors: Li Liang , Wang Hao , Gago Jorge , Cui Haiying , Qian Zhengjiang , Kodama Naomi , Ji Hongtao , Tian Shan , Shen Dan , Chen Yanjuan , Sun Fengli , Xia Zhonglan , Ye Qing , Sun Wei , Flexas Jaume , Dong Hansong
Published: November 2015

Harpin proteins produced by plant-pathogenic Gram-negative bacteria are the venerable player in regulating bacterial virulence and inducing plant growth and defenses. A major gap in these effects is plant sensing linked to cellular responses and plant sensor for harpin Hpa1 from rice bacterial blight pathogen points to plasma membrane intrinsic protein (PIP). Here we show that Arabidopsis AtPIP1;4 is a plasma membrane sensor of Hpa1 and plays a dual role in plasma membrane permeability of CO2 and H2O. In particular, AtPIP1;4 mediates CO2 transport with a substantial contribute to photosynthesis and further increases this function upon interacting with Hpa1 at the plasma membrane. As a result, leaf photosynthesis rates are increased and the plant growth is enhanced in contrast to the normal process without Hpa1-AtPIP1;4 interaction. Our findings demonstrate the first case that plant sensing of a bacterial harpin protein is connected with photosynthetic physiology to regulate plant growth.
Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target
Authors: Chiba Shuntaro , Ikeda Kazuyoshi , Ishida Takashi , Gromiha M. Michael , Taguchi Y-h. , Iwadate Mitsuo , Umeyama Hideaki , Hsin Kun-Yi , Kitano Hiroaki , Yamamoto Kazuki , Sugaya Nobuyoshi , Kato Koya , Okuno Tatsuya , Chikenji George , Mochizuki Masahiro , Yasuo Nobuaki , Yoshino Ryunosuke , Yanagisawa Keisuke , Ban Tomohiro , Teramoto Reiji , Ramakrishnan Chandrasekaran , Thangakani A. Mary , Velmurugan D. , Prathipati Philip , Ito Junichi , Tsuchiya Yuko , Mizuguchi Kenji , Honma Teruki , Hirokawa Takatsugu , Akiyama Yutaka , Sekijima Masakazu
Published: November 2015

A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective.
Formation of Nanotwin Networks during High-Temperature Crystallization of Amorphous Germanium
Authors: Sandoval Luis , Reina Celia , Marian Jaime
Published: November 2015

Germanium is an extremely important material used for numerous functional applications in many fields of nanotechnology. In this paper, we study the crystallization of amorphous Ge using atomistic simulations of critical nano-metric nuclei at high temperatures. We find that crystallization occurs by the recurrent transfer of atoms via a diffusive process from the amorphous phase into suitably-oriented crystalline layers. We accompany our simulations with a comprehensive thermodynamic and kinetic analysis of the growth process, which explains the energy balance and the interfacial growth velocities governing grain growth. For the 〈111〉 crystallographic orientation, we find a degenerate atomic rearrangement process, with two zero-energy modes corresponding to a perfect crystalline structure and the formation of a Σ3 twin boundary. Continued growth in this direction results in the development a twin network, in contrast with all other growth orientations, where the crystal grows defect-free. This particular mechanism of crystallization from amorphous phases is also observed during solid-phase epitaxial growth of 〈111〉 semiconductor crystals, where growth is restrained to one dimension. We calculate the equivalent X-ray diffraction pattern of the obtained nanotwin networks, providing grounds for experimental validation.
A chimeolysin with extended-spectrum streptococcal host range found by an induced lysis-based rapid screening method
Authors: Yang Hang , Linden Sara B. , Wang Jing , Yu Junping , Nelson Daniel C. , Wei Hongping
Published: November 2015

The increasing emergence of multi-drug resistant streptococci poses a serious threat to public health worldwide. Bacteriophage lysins are promising alternatives to antibiotics; however, their narrow lytic spectrum restricted to closely related species is a central shortcoming to their translational development. Here, we describe an efficient method for rapid screening of engineered chimeric lysins and report a unique “chimeolysin”, ClyR, with robust activity and an extended-spectrum streptococcal host range against most streptococcal species, including S. pyogenes, S. agalactiae, S. dysgalactiae, S. equi, S. mutans, S. pneumoniae, S. suis and S. uberis, as well as representative enterococcal and staphylococcal species (including MRSA and VISA). ClyR is the first lysin that demonstrates activity against the dominant dental caries-causing pathogen as well as the first lysin that kills all four of the bovine mastitis-causing pathogens. This study demonstrates the success of the screening method resulting in a powerful lysin with potential for treating most streptococcal associated infections.
The Molecular Karyotype of 25 Clinical-Grade Human Embryonic Stem Cell Lines
Authors: Canham Maurice A. , Van Deusen Amy , Brison Daniel R. , De Sousa Paul A. , Downie Janet , Devito Liani , Hewitt Zoe A. , Ilic Dusko , Kimber Susan J. , Moore Harry D. , Murray Helen , Kunath Tilo
Published: November 2015

The application of human embryonic stem cell (hESC) derivatives to regenerative medicine is now becoming a reality. Although the vast majority of hESC lines have been derived for research purposes only, about 50 lines have been established under Good Manufacturing Practice (GMP) conditions. Cell types differentiated from these designated lines may be used as a cell therapy to treat macular degeneration, Parkinson’s, Huntington’s, diabetes, osteoarthritis and other degenerative conditions. It is essential to know the genetic stability of the hESC lines before progressing to clinical trials. We evaluated the molecular karyotype of 25 clinical-grade hESC lines by whole-genome single nucleotide polymorphism (SNP) array analysis. A total of 15 unique copy number variations (CNVs) greater than 100 kb were detected, most of which were found to be naturally occurring in the human population and none were associated with culture adaptation. In addition, three copy-neutral loss of heterozygosity (CN-LOH) regions greater than 1 Mb were observed and all were relatively small and interstitial suggesting they did not arise in culture. The large number of available clinical-grade hESC lines with defined molecular karyotypes provides a substantial starting platform from which the development of pre-clinical and clinical trials in regenerative medicine can be realised.
Identification of a novel cathelicidin antimicrobial peptide from ducks and determination of its functional activity and antibacterial mechanism
Authors: Gao Wei , Xing Liwei , Qu Pei , Tan Tingting , Yang Na , Li Dan , Chen Huixian , Feng Xingjun
Published: November 2015

The family of antimicrobial peptide, cathelicidins, which plays important roles against infections in animals, has been identified from many species. Here, we identified a novel avian cathelicidin ortholog from ducks and named dCATH. The cDNA sequence of dCATH encodes a predicted 146-amino-acid polypeptide composed of a 17-residue signal peptide, a 109-residue conserved cathelin domain and a 20-residue mature peptide. Phylogenetic analysis demonstrated that dCATH is highly divergent from other avian peptides. The α-helical structure of the peptide exerted strong antimicrobial activity against a broad range of bacteria in vitro, with most minimum inhibitory concentrations in the range of 2 to 4 μM. Moreover, dCATH also showed cytotoxicity, lysing 50% of mammalian erythrocytes in the presence or absence of 10% fetal calf serum at concentrations of 32 μM or 20 μM and killing 50% HaCaT cells at a concentration of 10 μM. The effects on bacterial outer and inner membranes, as examined by scanning electron microscope and transmission electron microscopy, indicate that dCATH kills microbial cells by increasing permeability, causing a loss of membrane integrity.