bluuebunny/crossref_metadata_2025 huggingface dataset:
MELK-T1, a small-molecule inhibitor of protein kinase MELK, decreases DNA-damage tolerance in proliferating cancer cells
Authors: Beke Lijs , Kig Cenk , Linders Joannes T. M. , Boens Shannah , Boeckx An , van Heerde Erika , Parade Marc , De Bondt An , Van den Wyngaert Ilse , Bashir Tarig , Ogata Souichi , Meerpoel Lieven , Van Eynde Aleyde , Johnson Christopher N. , Beullens Monique , Brehmer Dirk , Bollen Mathieu
Published: October 2015

Maternal embryonic leucine zipper kinase (MELK), a serine/threonine protein kinase, has oncogenic properties and is overexpressed in many cancer cells. The oncogenic function of MELK is attributed to its capacity to disable critical cell-cycle checkpoints and reduce replication stress. Most functional studies have relied on the use of siRNA/shRNA-mediated gene silencing. In the present study, we have explored the biological function of MELK using MELK-T1, a novel and selective small-molecule inhibitor. Strikingly, MELK-T1 triggered a rapid and proteasome-dependent degradation of the MELK protein. Treatment of MCF-7 (Michigan Cancer Foundation-7) breast adenocarcinoma cells with MELK-T1 induced the accumulation of stalled replication forks and double-strand breaks that culminated in a replicative senescence phenotype. This phenotype correlated with a rapid and long-lasting ataxia telangiectasia-mutated (ATM) activation and phosphorylation of checkpoint kinase 2 (CHK2). Furthermore, MELK-T1 induced a strong phosphorylation of p53 (cellular tumour antigen p53), a prolonged up-regulation of p21 (cyclin-dependent kinase inhibitor 1) and a down-regulation of FOXM1 (Forkhead Box M1) target genes. Our data indicate that MELK is a key stimulator of proliferation by its ability to increase the threshold for DNA-damage tolerance (DDT). Thus, targeting MELK by the inhibition of both its catalytic activity and its protein stability might sensitize tumours to DNA-damaging agents or radiation therapy by lowering the DNA-damage threshold.
Spontaneous baroreceptor reflex sensitivity for risk stratification of heart failure patients: optimal cut-off and age effects
Authors: Gouveia Sónia , Scotto Manuel G. , Pinna Gian Domenico , Maestri Roberto , La Rovere Maria Teresa , Ferreira Paulo J.S.G.
Published: October 2015

Baroreceptor reflex sensitivity (BRS) is an important prognostic factor because a reduced BRS has been associated with an adverse cardiovascular outcome. The threshold for a ‘reduced’ BRS was established by the ATRAMI study at BRS <3 ms/mmHg in patients with a previous myocardial infarction, and has been shown to improve risk assessment in many other cardiac dysfunctions. The successful application of this cut-off to other populations suggests that it may reflect an inherent property of baroreflex functioning, so our goal is to investigate whether it represents a ‘natural’ partition of BRS values. As reduced baroreflex responsiveness is also associated with ageing, we investigated whether a BRS estimate <3 ms/mmHg could be the result of a process of physiological senescence as well as a sign of BRS dysfunction. This study involved 228 chronic heart failure patients and 60 age-matched controls. Our novel method combined transfer function BRS estimation and automatic clustering of BRS probability distributions, to define indicative levels of different BRS activities. The analysis produced a fit clustering (cophenetic correlation coefficient 0.9 out of 1) and identified one group of homogeneous patients (well separated from the others by 3 ms/mmHg) with an increased BRS-based mortality risk [hazard ratio (HR): 3.19 (1.73, 5.89), P<0.001]. The age-dependent BRS cut-off, estimated by 5% quantile regression of log (BRS) with age (considering the age-matched controls), provides a similar mortality value [HR: 2.44 (1.37, 4.43), P=0.003]. In conclusion, the 3 ms/mmHg cut-off identifies two large clusters of homogeneous heart failure (HF) patients, thus supporting the hypothesis of a natural cut-off in the HF population. Furthermore, age was found to have no statistical impact on risk assessment, suggesting that there is no need to establish age-based cut-offs because 3 ms/mmHg optimally identifies patients at high mortality risk.
Surface hopping, transition state theory and decoherence. I. Scattering theory and time-reversibility
Authors: Jain Amber , Herman Michael F. , Ouyang Wenjun , Subotnik Joseph E.
Published: October 2015

We provide an in-depth investigation of transmission coefficients as computed using the augmented-fewest switches surface hopping algorithm in the low energy regime. Empirically, microscopic reversibility is shown to hold approximately. Furthermore, we show that, in some circumstances, including decoherence on top of surface hopping calculations can help recover (as opposed to destroy) oscillations in the transmission coefficient as a function of energy; these oscillations can be studied analytically with semiclassical scattering theory. Finally, in the spirit of transition state theory, we also show that transmission coefficients can be calculated rather accurately starting from the curve crossing point and running trajectories forwards and backwards.
Thin film interface stresses produced by high amplitude laser generated surface acoustic waves
Authors: Sherman Bradley , Liou Hong-Cin , Balogun Oluwaseyi
Published: October 2015

Surface acoustic waves (SAWs) have been explored for nondestructive metrology of thin film elastic properties and thickness due to confinement of their energy within a shallow depth from a material surface. In this paper, we study the dynamic interfacial stresses produced by high amplitude SAWs generated by a strongly ablative source in a thin film-substrate system, with the goal of investigating the possibility of inducing thin film delamination at high loading rates. For modeling purposes, we represent the mechanical loading resulting from the pulsed laser-sample interaction in the ablative regime by an equivalent compressive surface load, and the resulting stresses and particle velocities induced by the generated SAWs are calculated using a linear finite element model. We explore the numerical model to study the dependence of the film-substrate interface tractions on the ratio of the film thickness and SAW wavelength for a soft film on a stiff substrate. Furthermore, by matching the numerical results obtained from the finite element model with experimental results, we are able to predict the dynamic interfacial stresses for a copper film on a fused silica substrate produced by SAWs excited by a high power pulsed laser line source. This study has implications for exploring SAWs in the characterization of interfacial failure in thin-film substrate systems.
The linear and non-linear characterization of dust ion acoustic mode in complex plasma in presence of dynamical charging of dust
Authors: Bhattacharjee Saurav , Das Nilakshi
Published: October 2015

A systematic theoretical investigation has been carried out on the role of dust charging dynamics on the nature and stability of DIA (Dust Ion Acoustic) mode in complex plasma. The study has been made for both linear and non-linear scale regime of DIA mode. The observed results have been characterized in terms of background plasma responses towards dust surface responsible for dust charge fluctuation, invoking important dusty plasma parameters, especially the ion flow speed and dust size. The linear analyses confirm the nature of instability in DIA mode in presence of dust charge fluctuation. The instability shows a damping of DIA mode in subsonic flow regime followed by a gradual growth in instability in supersonic limit of ion flow. The strength of non-linearity and their existence domain is found to be driven by different dusty plasma parameters. As dust is ubiquitous in interstellar medium with plasma background, the study also addresses the possible effect of dust charging dynamics in gravito-electrostatic characterization and the stability of dust molecular clouds especially in proto-planetary disc. The observations are influential and interesting towards the understanding of dust settling mechanism and formation of dust environments in different regions in space.
Synthesis of nanoparticles in helium droplets—A characterization comparing mass-spectra and electron microscopy data
Authors: Thaler Philipp , Volk Alexander , Knez Daniel , Lackner Florian , Haberfehlner Georg , Steurer Johannes , Schnedlitz Martin , Ernst Wolfgang E.
Published: October 2015

Micrometer sized helium droplets provide an extraordinary environment for the growth of nanoparticles. The method promises great potential for the preparation of core-shell particles as well as one-dimensional nanostructures, which agglomerate along quantum vortices, without involving solvents, ligands, or additives. Using a new apparatus, which enables us to record mass spectra of heavy dopant clusters (>104 amu) and to produce samples for transmission electron microscopy simultaneously, we synthesize bare and bimetallic nanoparticles consisting of various materials (Au, Ni, Cr, and Ag). We present a systematical study of the growth process of clusters and nanoparticles inside the helium droplets, which can be described with a simple theoretical model.
Ionic liquids—Conventional solvent mixtures, structurally different but dynamically similar
Authors: Araque Juan C. , Hettige Jeevapani J. , Margulis Claudio J.
Published: October 2015

In more than one way pure ionic liquids (ILs) can be seen as mixtures. By definition they are comprised of cationic and anionic components and they also possess dual charge and apolar characteristics. We recently uncovered interesting dynamical behavior [Araque et al., J. Phys. Chem. B 119(23), 7015 (2015)] that can be ascribed to this duality. For small neutral solutes local friction can be high in certain regions and much lower in others. It is only reasonable to ask whether this interesting behavior is unique to ILs or is also common in certain conventional solvent mixtures such as dimethylsufoxide/glycerol for which the viscosity can be tuned to be similar. We make the case that the latter scenario is correct and that whereas viscous conventional solvent mixtures are structurally very different from ILs, dynamically they are not. From the perspective of a solute that is small, both ILs and viscous conventional solvent mixtures display frictionally stiff and soft regions associated with cage and jump diffusive regimes. In the case of ILs these are associated with charge-enhanced and charge-depleted liquid regions, whereas in the case of the conventional solvents by the distinct frictional properties of the two components.
Localized electron heating by strong guide-field magnetic reconnection
Authors: Guo Xuehan , Inomoto Michiaki , Sugawara Takumichi , Yamasaki Kotaro , Ushiki Tomohiko , Ono Yasushi ,   TS Group
Published: October 2015

Localized electron heating of magnetic reconnection was studied under strong guide-field using two merging spherical tokamak plasmas in the University of Tokyo Spherical Tokamak experiment. Our new slide-type two-dimensional Thomson scattering system is documented for the first time the electron heating localized around the X-point. Shape of the high electron temperature area does not agree with that of energy dissipation term Et·jt. If we include a guide-field effect term Bt/(Bp+αBt) for Et·jt, the energy dissipation area becomes localized around the X-point, suggesting that the electrons are accelerated by the reconnection electric field parallel to the magnetic field and thermalized around the X-point.
Space charge induced electrostatic doping of two-dimensional materials: Graphene as a case study
Authors: Paradisi Andrea , Biscaras Johan , Shukla Abhay
Published: October 2015

We introduce a technique that we call Space Charge Doping for electrostatic doping of 2D materials. This technique exploits the presence of mobile ionic species in glass to induce a charge imbalance at the glass-material interface. Ionic mobility in glass is species dependent and also dependent on the temperature and the applied electric field. Mobility of positive sodium ions is increased by heating and an applied electric field causes ion drift. The polarity of the electric field results in accumulation or depletion of sodium ions at the glass surface inducing, respectively, electron or hole doping in the material placed on the surface, in this case graphene. Extremely high doping levels are reached (>1014 cm−2) without compromising graphene quality and with reversibility, bipolarity, and stability in time.
Motion of free-surface of shock-compressed water on emergence of rarefaction
Authors: Menezes V. , Hosseini H. , Moosavi-Nejad S. , Irimpan K. J. , Akiyama H.
Published: October 2015

We experimentally evaluated the impulsive motion of free-surface of water on impingement of shock-waves of moderate strength. This physical process creates the initial acceleration in shock-wave based micro-fluidic devices, which have promising medical and drug/DNA delivery applications. The velocities of the water interfaces were measured through real-time high-temporal/spatial resolution visualizations. Based on modified Tait equation-of-state and the concept of Reimann-invariants, an analytical expression was deduced to calculate the particle velocity behind the unloading wave. The experiments and analyses confirm that the mass motion behind the shock-wave accelerates to very high velocities, a requirement for effective momentum delivery in micro-jet devices.
Broadband dielectric spectra in PbMg1/3Nb2/3O3 crystals with chemical order modified by La doping
Authors: Jablonskas D. , Grigalaitis R. , Banys J. , Bokov A. A. , Ye Z.-G.
Published: October 2015

PbMg1/3Nb2/3O3 (PMN) is a well known ferroelectric relaxor. PMN crystal doped with La3+ has greatly enlarged chemically ordered regions (CORs) in the structure. It is interesting to know how the development of CORs influences physical properties of PMN crystal. In this work, dielectric properties and distribution of relaxation times of PMN and 0.98Pb(Mg1/3Nb2/3)O3–0.02La(Mg2/3Nb1/3)O3 (PLMN) crystals are studied. The experiment was performed in 120–500 K temperature range and wide frequency range—up to 46 GHz. The results demonstrate that the relaxor behaviour of PMN and PLMN is qualitatively the same in spite of the fact that chemical ordering is very different.
Genome-wide modeling of transcription kinetics reveals patterns of RNA production delays
Authors: Honkela Antti , Peltonen Jaakko , Topa Hande , Charapitsa Iryna , Matarese Filomena , Grote Korbinian , Stunnenberg Hendrik G. , Reid George , Lawrence Neil D. , Rattray Magnus
Published: October 2015

Significance

Gene transcription is a highly regulated dynamic process. Delays in transcription have important consequences on dynamics of gene expression and consequently on downstream biological function. We model temporal dynamics of transcription using genome-wide time course data measuring transcriptional activity and mRNA concentration. We find a significant number of genes exhibit a long RNA processing delay between transcription termination and mRNA production. These long processing delays are more common for short genes, which would otherwise be expected to transcribe most rapidly. The distribution of intronic reads suggests that these delays are required for splicing to be completed. Understanding such delays is essential for understanding how a rapid cellular response is regulated.
NO binding kinetics in myoglobin investigated by picosecond Fe K-edge absorption spectroscopy
Authors: Silatani Mahsa , Lima Frederico A. , Penfold Thomas J. , Rittmann Jochen , Reinhard Marco E. , Rittmann-Frank Hannelore M. , Borca Camelia , Grolimund Daniel , Milne Christopher J. , Chergui Majed
Published: October 2015

Significance

This work is the first demonstration, to our knowledge, of picosecond X-ray absorption spectroscopy to probe ligand binding to heme proteins in physiological media. By Fe K-edge absorption spectroscopy, we directly interrogate the active center of the protein, delivering insight into its electronic and geometric structure. In particular, we have investigated the evolution of the Fe center after photodissociation of NO from nitrosylmyoglobin (MbNO) and observed an intermediate over hundreds of picoseconds, which we propose to be the domed ligated form of MbNO that is formed on recombination of NO to the Fe atom. This work opens the way to a detailed investigation of metalloproteins using subpicosecond X-ray spectroscopy at free electron lasers.
Allowing variance may enlarge the safe operating space for exploited ecosystems
Authors: Carpenter Stephen R. , Brock William A. , Folke Carl , van Nes Egbert H. , Scheffer Marten
Published: October 2015

Significance

Humans depend on ecosystems for food, water, pharmaceuticals, and other benefits. Ecosystem managers, industries, and the public want these benefits to be predictable and therefore have low variance over time. However, control of variance for short-term benefits leads to long-term fragility. Here we show that management to reduce short-term variability can drive ecosystems into degraded states, leading to long-term declines of ecosystem services. These risks can be avoided by strategies that tolerate variability within boundaries of safe operating spaces for ecosystem management.
A runner’s high depends on cannabinoid receptors in mice
Authors: Fuss Johannes , Steinle Jörg , Bindila Laura , Auer Matthias K. , Kirchherr Hartmut , Lutz Beat , Gass Peter
Published: October 2015

Significance

A runner’s high is a subjective sense of well-being some humans experience after prolonged exercise. For decades, it was hypothesized that exercise-induced endorphin release is solely responsible for a runner’s high, but recent evidence has suggested that endocannabinoids also may play a role. Here, we demonstrate that wheel running increases endocannabinoids and reduces both anxiety and sensation of pain in mice. Ablation of cannabinoid receptor 1 receptors on GABAergic neurons inhibits running-induced anxiolysis, and pharmacological blockage of central and peripheral cannabinoid receptors inhibits analgesia. We thus show for the first time to our knowledge that cannabinoid receptors are crucial for main aspects of a runner’s high.
Glycoprotein B7-H3 overexpression and aberrant glycosylation in oral cancer and immune response
Authors: Chen Jung-Tsu , Chen Chein-Hung , Ku Ko-Li , Hsiao Michael , Chiang Chun-Pin , Hsu Tsui-Ling , Chen Min-Huey , Wong Chi-Huey
Published: October 2015

Significance

Oral squamous cell carcinoma (OSCC) is characterized by high morbidity and mortality, and few therapeutic options. Here, we show that the expression of B7 Homolog 3 (B7-H3) is significantly up-regulated in the tumor tissue of OSCC patients and correlated with increased tumor size and poor survival rate. Comparing the N-glycans of B7-H3 from Ca9-22 oral cancer cells and Smulow–Glickman (SG) normal cells, we also found that the glycans of B7-H3 from Ca9-22 contain the terminal α-galactose and are more diverse with higher fucosylation and better interaction with immune cells. These findings indicate that glycoprotein B7-H3 is an important marker in oral cancer and its overexpression and aberrant glycosylation may provide a direction for the development of diagnosis and treatment of oral cancer.
Degrees of irreducible characters of the symmetric group and exponential growth
Authors: Giambruno Antonio , Mishchenko Sergey
Published: October 2015

We consider sequences of degrees of ordinary irreducible

S
n

S_n

- characters. We assume that the corresponding Young diagrams have rows and columns bounded by some linear function of

n
n

with leading coefficient less than one. We show that any such sequence has at least exponential growth and we compute an explicit bound.
The Subaru–XMM-Newton Deep Survey (SXDS). VIII. Multi-wavelength identification, optical/NIR spectroscopic properties, and photometric redshifts of X-ray sources
Authors: Akiyama Masayuki , Ueda Yoshihiro , Watson Mike G. , Furusawa Hisanori , Takata Tadafumi , Simpson Chris , Morokuma Tomoki , Yamada Toru , Ohta Kouji , Iwamuro Fumihide , Yabe Kiyoto , Tamura Naoyuki , Moritani Yuuki , Takato Naruhisa , Kimura Masahiko , Maihara Toshinori , Dalton Gavin , Lewis Ian , Lee Hanshin , Curtis-Lake Emma , Macaulay Edward , Clarke Frazer , Silverman John D. , Croom Scott , Ouchi Masami , Hanami Hitoshi , Díaz Tello Jorge , Yoshikawa Tomohiro , Fujishiro Naofumi , Sekiguchi Kazuhiro
Published: October 2015

We report on the multi-wavelength identification of the X-ray sources found in the Subaru–XMM-Newton Deep Survey (SXDS) using deep imaging data covering the wavelength range between the far-UV and mid-IR (MIR). We select a primary counterpart of each X-ray source by applying the likelihood ratio method to R-band, 3.6 μm, near-UV, and 24 μm source catalogs as well as matching catalogs of active galactic nucleus (AGN) candidates selected in 1.4 GHz radio and i ′-band variability surveys. Once candidates for Galactic stars, ultra-luminous X-ray sources in a nearby galaxy, and clusters of galaxies are removed there are 896 AGN candidates in the sample. We conduct spectroscopic observations of the primary counterparts with multi-object spectrographs in the optical and NIR; 65% of the X-ray AGN candidates are spectroscopically identified. For the remaining X-ray AGN candidates, we evaluate their photometric redshift with photometric data in 15 bands. Utilizing the multi-wavelength photometric data of the large sample of X-ray-selected AGNs, we evaluate the stellar masses, M*, of the host galaxies of the narrow-line AGNs. The distribution of the stellar mass is remarkably constant from z = 0.1 to 4.0. The relation between M* and 2–10 keV luminosity can be explained with strong cosmological evolution of the relationship between the black hole mass and M*. We also evaluate the scatter of the UV–MIR spectral energy distribution (SED) of the X-ray AGNs as a function of X-ray luminosity and absorption by the nucleus. The scatter is compared with galaxies which have redshift and stellar mass distribution matched with the X-ray AGN. The UV–NIR (near-IR) SEDs of obscured X-ray AGNs are similar to those of the galaxies in the matched sample. In the NIR–MIR range, the median SEDs of X-ray AGNs are redder, but the scatter of the SEDs of the X-ray AGN broadly overlaps that of the galaxies in the matched sample.
ZNF1 Encodes a Putative C2H2 Zinc-Finger Protein Essential for Appressorium Differentiation by the Rice Blast Fungus Magnaporthe oryzae
Authors: Yue Xiaofeng , Que Yawei , Xu Lin , Deng Shuzhen , Peng Youliang , Talbot Nicholas J. , Wang Zhengyi
Published: October 2015

The rice blast fungus Magnaporthe oryzae forms specialized infection structures called appressoria which are essential for gaining entry to plant tissue. Here, we report the identification of a novel nonpathogenic T-DNA-tagged mutant XF696 of M. oryzae with a single insertion in the promoter of ZNF1, which encodes a putative transcription factor (TF). Targeted gene deletion mutants of ZNF1 are nonpathogenic and unable to develop appressoria. However, Δznf1 mutants still respond to exogenous cyclic AMP on hydrophilic surfaces and can sense hydrophobic surfaces, initiating the differentiation of germ tubes. Interestingly, Δznf1 mutants also produce significantly more conidia compared with the isogenic wild-type strain. Quantitative reverse-transcription polymerase chain reaction analysis and green fluorescent protein fusion experiments revealed that expression of ZNF1 was highly induced during germination and appressorium development in M. oryzae and potentially regulated by the Pmk1 mitogen-activated protein kinase pathway. We observed that Δznf1 mutants are affected in mitosis and impaired in mobilization and degradation of lipid droplets and glycogen reserves during appressorium differentiation. Site-directed mutagenesis confirmed that three of the four C2H2 zinc-finger domains are essential for the function of Znf1. Taken together, we conclude that a C2H2 zinc-finger TF encoded by ZNF1 is essential for appressorium development by the rice blast fungus.
Complete firing-rate response of neurons with complex intrinsic dynamics
Authors: Puelma Touzel Maximilian A , Wolf Fred
Published: October 2015

The response of a neuronal population over a space of inputs depends on the intrinsic properties of its constituent neurons. Two main modes of single neuron dynamics integration and resonance have been distinguished. While resonator cell types exist in a variety of brain areas, few models incorporate this feature and fewer have investigated its effects. To understand better how a resonator's frequency preference emerges from its intrinsic dynamics and contributes to its local area's population firing rate dynamics, we analyze the dynamic gain of an analytically solvable two-degree of freedom neuron model. In the Fokker-Planck approach, the dynamic gain is intractable. The alternative Gauss-Rice approach lifts the resetting of the voltage after a spike. This allows us to derive a complete expression for the dynamic gain of a resonator neuron model in terms of a cascade of filters on the input. We find six distinct response types and use them to fully characterize the routes to resonance across all values of the relevant timescales. We find that resonance arises primarily due to slow adaptation with an intrinsic frequency acting to sharpen and adjust the location of the resonant peak. We determine the parameter regions for the existence of an intrinsic frequency and for subthreshold and spiking resonance, finding all possible intersections of the three. The expressions and analysis presented here provide an account of how intrinsic neuron dynamics shape dynamic population response properties and can facilitate the construction of an exact theory of correlations and stability of population activity in networks containing populations of resonator neurons.
Habitat Fluctuations Drive Species Covariation in the Human Microbiota
Authors: Fisher Charles K. , Mora Thierry , Walczak Aleksandra M.
Published: October 2015

Two species with similar resource requirements respond in a characteristic way to variations in their habitat – their abundances rise and fall in concert. We use this idea to learn how bacterial populations in the microbiota respond to habitat conditions that vary from person-to-person across the human population. Our mathematical framework shows that habitat fluctuations are sufficient for explaining intra-bodysite correlations in relative species abundances from the Human Microbiome Project. We explicitly show that the relative abundances of phylogenetically related species are positively correlated and can be predicted from taxonomic relationships. We identify a small set of functional pathways related to metabolism and maintenance of the cell wall that form the basis of a common resource sharing niche space of the human microbiota.
From pots to plots: hierarchical trait‐based prediction of plant performance in a mesic grassland
Authors: Schroeder‐Georgi Thomas , Wirth Christian , Nadrowski Karin , Meyer Sebastian T. , Mommer Liesje , Weigelt Alexandra
Published: October 2015

Traits are powerful predictors of ecosystem functions pointing to underlying physiological and ecological processes. Plant individual performance results from the coordinated operation of many processes, ranging from nutrient uptake over organ turnover to photosynthesis, thus requiring a large set of traits for its prediction. For plant performance on higher hierarchical levels, e.g. populations, additional traits important for plant‐plant and trophic interactions may be required which should even enlarge the spectrum of relevant predictor traits.

The goal of this study was to assess the importance of plant functional traits to predict individual and population performance of grassland species with particular focus on the significance of root traits. We tested this for 59 grassland species using 35 traits divided into three trait clusters: leaf traits (16), stature traits (8) and root traits (11), using individual biomass of mesocosm plants as a measure of individual performance and population biomass of monocultures as a measure of population performance. We applied structural equation models to disentangle direct effects of single traits on population biomass and indirect effects via individual plant biomass or shoot density.We tested multivariate trait effects on individual and population biomass to analyse whether the importance of different trait clusters shifts with increasing hierarchical integration from individuals to populations.

Traits of all three clusters significantly correlated with individual and population biomass. However, in spite of a number of significant correlations, above‐below‐ground linkages were generally weak, with few exceptions like N content.

Stature traits exclusively affected population biomass indirectly via their effect on individual biomass, whereas root and leaf traits showed also direct effects and partly indirect effects via density.

The inclusion of root traits in multiple regression models improved the prediction of individual biomass when compared with models with only above‐ground information only slightly (95% vs. 93% of variance prediction with and without root traits, respectively) but was crucial for the prediction of population biomass (77% and 49%, respectively). Root traits were more important for plant performance than leaf traits and were even the most important predictors at the population level

Synthesis. Upscaling from the individual to the population level reflects an increasing number of processes requiring traits from different trait clusters for their prediction. Our results emphasize the importance of root traits for trait‐based studies especially at higher organizational levels. Our approach provides a comprehensive framework acknowledging the hierarchical nature of trait influences. This is one step towards a more process‐oriented assessment of trait‐based approaches.
Novel viral genomes identified from six metagenomes reveal wide distribution of archaeal viruses and high viral diversity in terrestrial hot springs
Authors: Gudbergsdóttir Sóley Ruth , Menzel Peter , Krogh Anders , Young Mark , Peng Xu
Published: October 2015

Limited by culture‐dependent methods the number of viruses identified from thermophilic Archaea and Bacteria is still very small. In this study we retrieved viral sequences from six hot spring metagenomes isolated worldwide, revealing a wide distribution of four archaeal viral families, Ampullaviridae, Bicaudaviridae, Lipothrixviridae and Rudiviridae. Importantly, we identified 10 complete or near complete viral genomes allowing, for the first time, an assessment of genome conservation and evolution of the Ampullaviridae family as well as Sulfolobus Monocaudavirus 1 (SMV1)‐related viruses. Among the novel genomes, one belongs to a putative thermophilic virus infecting the bacterium Hydrogenobaculum, for which no virus has been reported in the literature. Moreover, a high viral diversity was observed in the metagenomes, especially among the Lipothrixviridae, as indicated by the large number of unique contigs and the lack of a completely assembled genome for this family. This is further supported by the large number of novel genes in the complete and partial genomes showing no sequence similarities to public databases. CRISPR analysis revealed hundreds of novel CRISPR loci and thousands of novel CRISPR spacers from each metagenome, reinforcing the notion of high viral diversity in the thermal environment.
Europe Needs Consistent Teaching of the Economics of Animal Health
Authors: Jackson Elizabeth L. , Waret‐Szkuta Agnès , Raboisson Didier , Niemi Jarkko , Aragrande Maurizio , Gethmann Jörn , Martins Sara Babo , Höreth‐Böntgen Detlef , Sans Pierre , Stärk Katharina D. , Häsler Barbara , Rushton Jonathan
Published: October 2015

Education in the use of economics applied to animal health (EAH) has been offered as part of various veterinary degree programmes since the 1980s. However, it has never been institutionalised in under‐graduate curricula for animal health professionals and there is no systematic information on current teaching and education activities. An online survey was conducted in Europe to assess existing teaching programmes and the expectations of people using economics in animal health. The main conclusion is that there is insufficient EAH education on offer and there are disparate approaches to EAH‐related curricula. Respondents expressed concerns regarding for example the limited education relating to assessing economic impacts of animal diseases, evaluation of intervention decisions, or using economics for general business management and understanding markets. Both public and private organisations predicted an increasing need for EAH in the future. The overarching implication is that EAH teaching methods and materials need to be developed and philosophically embedded into animal health curricula to ensure that future policy decisions regarding animal health are based on strong, well‐founded knowledge of resource allocation.
Association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with preterm delivery and placental abruption: a systematic review and meta‐analysis
Authors: Chen Jian , Chen Liang , Zhu Li‐Hua , Zhang Si‐Tong , Wu Yi‐Le
Published: October 2015

Introduction

The aim of this study was to summarize evidence on the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and odds of preterm delivery and placental abruption.

Material and Methods

PubMed, EMBASE, CBM (Chinese Biomedical Database) and CNKI (Chinese National Knowledge Infrastructure) were searched to identify eligible studies published in English or Chinese before 12 August 2014. The pooled odds ratios (ORs) with 95% confidence intervals were estimated for the association of MTHFR C677T polymorphism with preterm delivery and placental abruption using random effects models.

Results

A total of 22 studies that met inclusion and exclusion criteria were included in this meta‐analysis. Regardless of the genetic model tested we found no statistically significant association of MTHFR C677T polymorphism with preterm delivery or placental abruption. Funnel plots inspections, Begg's test and Egger's test did not show evidence of publication bias.

Conclusions

This meta‐analysis demonstrated that overall there was no association of MTHFR C677T polymorphism with preterm delivery or placental abruption.
Clinical Weighting of Drug–Drug Interactions in Hospitalized Elderly
Authors: Juárez‐Cedillo Teresa , Martinez‐Hernández Cynthia , Hernández‐Constantino Angel , Garcia‐Cruz Juan Carlos , Avalos‐Mejia Annia M , Sánchez‐Hurtado Luis A. , Islas Perez Valentin , Hansten Philip D.
Published: October 2015

Adverse drug reactions impact on patient health, effectiveness of pharmacological therapy and increased health care costs. This investigation intended to detect the most critical drug–drug interactions in hospitalized elderly patients, weighting clinical risk. We conducted a cross‐sectional study between January and April 2014; all patients 70 years or older, hospitalized for >24 hr and prescribed at least one medication were included in the study. Drug–drug interactions were estimated by combining Stockley's, Hansten and Tatro drug interactions. Drug–drug interactions were weighted using a risk‐analysis method based on failure modes, effects and criticality analysis. We calculated a criticality index for each drug involved in the drug–drug interactions based on the severity of the interaction mechanism, the frequency the drug was involved in drug–drug interactions and the risk of drug–drug interactions in patients with impaired renal function. The average number of drugs consumed in the hospital was 6 ± 2.69, involving 160 active ingredients. The most frequent were as follows: Furosemide, followed by Enalapril. Of drug–drug interactions, 2% were classified as contraindicated, 14% advised against and 83% advised caution during the hospital stay. Thirty‐four drug–drug interactions were assessed, of which 23 were pharmacodynamic drug–drug interactions and 12 were pharmacokinetic drug–drug interactions (1 was both). The clinical risk calculated for each drug–drug interaction included heparins + non‐steroidal anti‐inflammatory drugs (NSAIDs) or Digoxin + Calcium Gluconate, cases which are pharmacodynamic drug–drug interactions with agonist effect and clinical risk of bleeding, one of the most common clinical risks in the hospital. An index of clinical risk for drug–drug interactions can be calculated based on severity by the interaction mechanism, the frequency that the drug is involved in drug–drug interactions and the risk of drug–drug interactions in an elderly patient with impaired renal function.
ACROSCORE: a new and simple tool for the diagnosis of acromegaly, a rare and underdiagnosed disease
Authors: Prencipe Nunzia , Floriani Irene , Guaraldi Federica , Di Giacomo Stellina V. , Cannavo Salvatore , Arnaldi Giorgio , Berton Alessandro , Torri Valter , Spinello Maurizio , Arvat Emanuela , Ghigo Ezio , Grottoli Silvia
Published: October 2015

Objective

Acromegaly, a disease caused by GH/IGF‐I hypersecretion, is associated with a high mortality rate; early recognition is therefore necessary to ensure successful treatment and to avoid comorbidities. We have created a symptom/sign scoring tool (ACROSCORE) for physicians to use to identify acromegaly.

Design

To compare cases of acromegaly diagnosed between 1990 and 2014 against a control group affected by non‐GH‐secreting pituitary tumours to identify symptoms and signs that are most discriminative for acromegaly.

Patients

Confirmed acromegaly patients and patients affected by non‐GH‐secreting pituitary tumours.

Measurements

In all patients, signs, symptoms and comorbidities were recorded from medical records and collected using a specifically designed questionnaire.

Results

A total of 194 acromegaly patients [115 women; mean (SD) age 47·2 (14·2) years] and 243 patients affected by non‐GH‐secreting pituitary tumours [131 women; mean (SD) age 45·8 (15·8) years] were included. A strong association was observed for type 2/secondary diabetes [odds ratio (OR) 3·7], hyperhidrosis (OR 6·1), thyroid hyperplasia (OR 13·9), colorectal polyps (OR 10·4), spaced teeth (OR 25·4) and carpal tunnel syndrome (OR 4·3). Based on this information, a multivariable logistic model was built and a 14‐point scoring system developed. A score of 0 excludes the risk of acromegaly [positive predictive value (PV+) = 0·6%]; scores 1–5 comprise a grey area; scores >5 indicate that a diagnosis of acromegaly cannot be excluded (PV+ = 46·1%).

Conclusions

Once validated in independent studies, ACROSCORE may represent a new tool for the clinical screening of acromegaly that can be used by general practitioners and nonendocrinology specialists.
Evaluation of extrashort 4‐mm implants in mandibular edentulous patients with reduced bone height in comparison with standard implants: a 12‐month results
Authors: Calvo‐Guirado José Luis , López Torres José Alberto , Dard Michel , Javed Fawad , Pérez‐Albacete Martínez Carlos , Maté Sánchez de Val José Eduardo
Published: October 2015

Objective

The aim of this research was to evaluate the primary stability, the marginal bone loss, the survival, and the success criteria, of 4‐mm‐length implants compared with implants of conventional length supporting fixed prostheses.

Materials and Methods

Ten patients were selected for treatment of their atrophic edentulous jaws. Each patient received the following treatment: six dental implants were inserted, two anterior implants of conventional length (10‐mm) in the interforaminal area and four posterior short implants of 4‐mm length (Standard Plus, Roxolid, SLActive, Institut Straumann AG). The implants supported screw‐retained fixed complete dentures. Examinations were conducted at day 0, three, six, and twelve months after surgery for the evaluation of the implant primary stability, secondary stability, crestal bone loss and survival by clinical evaluations, insertion torque values, resonance frequency analysis (RFA), and periapical radiography, respectively.

Results

Sixty implants were inserted in ten patients. Mean insertion torque was slightly lower for 4‐mm implants than 10‐mm implants (38.1 Ncm vs. 42.2 Ncm) but without statistically significant difference. Implant stability was similar for extrashort and conventional implants. Marginal bone loss was similar for both groups for all the time periods. One short implant was lost before loading. The survival rates twelve months after implant placement were of 97.5% and 100% for short and conventional implants, respectively. Similarly, implant stability as measured byRFAwas nonsignificantly lower for the 4‐mm implants compared to the 10‐mm implants. The marginal bone loss was lower for short implants three, six, and twelve months after the surgery without statistical significant difference.

Conclusions

Within the limitations of this study, we conclude that short dental implants (8 mm or less in length) supporting single crowns or fixed bridges are a feasible treatment option with radiographic and clinical success rates similar to longer implants for patients with compromised ridges. Long‐term data with larger number of implants and subjects are needed to confirm these preliminary results.
Meaning is Not a Reflex: Context Dependence of Spatial Congruity Effects
Authors: Casasanto Daniel , Brookshire Geoffrey , Ivry Richard
Published: October 2015

In two experiments, Brookshire, Ivry, and Casasanto (2010) showed that words with positive and negative emotional valence can activate spatial representations with a high degree of automaticity, but also that this activation is highly context dependent. Lebois, Wilson‐Mendenhall, and Barsalou (2015) reported that they “aimed to replicate” our study but found only null results in the “Brookshire et al. replication” conditions. Here we express concerns about three aspects of this paper. First, the study was not an attempt to replicate ours; it was a different study that adapted our method. Second, Lebois et al. did not accurately represent our theoretical position. Third, Lebois et al.’s main conclusion, that spatial congruity effects depend on the task context, was not supported by their data. Despite these concerns, we agree with Lebois et al.'s overall message that spatial aspects of words' meanings are activated differently in different contexts. This was a main conclusion of our study as well.
Relative hypoaldosteronism in a patient with Wolcott‐Rallison syndrome
Authors: Uçar A. , Aydemir Y. , Doğan A. , Tunçez E.
Published: October 2015

Background

Wolcott‐Rallison syndrome is an autosomal recessive, multisystem disorder with onset of diabetes in the neonatal period or early infancy.

Case report

A 9‐year‐old girl with diabetes and growth failure from 2 months of age presented with ketoacidosis and multiple organ failure. Evaluation for short stature revealed epiphyseal dysplasia. A homozygous mutation in the EIF2AK3 gene confirmed the clinical diagnosis of Wolcott‐Rallison syndrome. She was euthyroid. Biochemical evaluation for potential adrenal dysfunction because of persistently elevated serum potassium (range 5.9–6.3 meq/l) and low serum sodium levels (range 128–130 meq/l) 2 weeks after resolution of ketoacidosis yielded normal findings with respect to basal corticotropin (31 pg/ml) and cortisol (18.7 μg/dl) levels. Estimated GFR‐Schwartz (36.9 ml/min/1.73 m2) was consistent with stage 3 chronic renal failure. The transtubular potassium gradient was 1.39 (normal value in hyperkalemic states: > 4.1). The plasma aldosterone (upright: 241.3 pmol/l) was within normal ranges, and plasma renin [39 pg/ml (range 5.41–34.53 pg/ml)] was slightly elevated. The patient was diagnosed as having relative hypoaldosteronism and was started on a sodium‐rich diet and low potassium. Failure to respond to the dietary intervention prompted a trial of oral fludrocortisone with subsequent normalization of electrolyte levels.

Conclusions

This is the first case report of Wolcott‐Rallison syndrome complicated with relative hypoaldosteronism. Further research is needed to probe the causal inference of relative hypoaldosteronism with chronic renal failure in patients with Wolcott‐Rallison syndrome.
Low alanine aminotransferase levels and higher number of cardiovascular events in people with Type 2 diabetes: analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study
Authors: Williams K. H. , Sullivan D. R. , Veillard A. S. , O'Brien R. , George J. , Jenkins A. J. , Young S. , Ehnholm C. , Duffield A. , Twigg S. M. , Keech A. C.
Published: October 2015

Aims

To determine whether alanine aminotransferase or gamma‐glutamyltransferase levels, as markers of liver health and non‐alcoholic fatty liver disease, might predict cardiovascular events in people with Type 2 diabetes.

Methods

Data from the Fenofibrate Intervention and Event Lowering in Diabetes study were analysed to examine the relationship between liver enzymes and incident cardiovascular events (non‐fatal myocardial infarction, stroke, coronary and other cardiovascular death, coronary or carotid revascularization) over 5 years.

Results

Alanine aminotransferase measure had a linear inverse relationship with the first cardiovascular event occurring in participants during the study period. After adjustment, for every 1 sdhigher baseline alanine aminotransferase measure (13.2 U/l), the risk of a cardiovascular event was 7% lower (95%CI4–13;P = 0.02). Participants with alanine aminotransferase levels below and above the reference range 8–41 U/l for women and 9–59 U/l for men, had hazard ratios for a cardiovascular event of 1.86 (95%CI1.12–3.09) and 0.65 (95%CI0.49–0.87), respectively (P = 0.001). No relationship was found for gamma‐glutamyltransferase.

Conclusions

The data may indicate that in people with Type 2 diabetes, which is associated with higher alanine aminotransferase levels because of prevalent non‐alcoholic fatty liver disease, a low alanine aminotransferase level is a marker of hepatic or systemic frailty rather than health.