bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear interaction of proton whistler with kinetic Alfvén wave to study solar wind turbulence
Authors: Goyal R. , Sharma R. P. , Goldstein M. L. , Dwivedi N. K.
Published: December 2013

This paper presents the nonlinear interaction between small but finite amplitude kinetic Alfvén wave (KAW) and proton whistler wave using two-fluid model in intermediate beta plasma, applicable to solar wind. The nonlinearity is introduced by modification in the background density. This change in density is attributed to the nonlinear ponderomotive force due to KAW. The solutions of the model equations, governing the nonlinear interaction (and its effect on the formation of localized structures), have been obtained using semi-analytical method in solar wind at 1AU. It is concluded that the KAW properties significantly affect the threshold field required for the filament formation and their critical size (for proton whistler). The magnetic and electric field power spectra have been obtained and their relevance with the recent observations of solar wind turbulence by Cluster spacecraft has been pointed out.
X-ray diffraction study on pressure-induced phase transformations and the equation of state of ZnGa2Te4
Authors: Errandonea D. , Kumar R. S. , Gomis O. , Manjón F. J. , Ursaki V. V. , Tiginyanu I. M.
Published: December 2013

We report on high-pressure x-ray diffraction measurements up to 19.8 GPa in zinc digallium telluride (ZnGa2Te4) at room temperature. An irreversible structural phase transition takes place at pressures above 12.1 GPa and upon decompression a third polymorph of ZnGa2Te4 was recovered as a metastable phase at pressures below 2.9 GPa. Rietveld refinements were carried out for the three detected polymorphs, being their possible crystal structures reported. The axial compressibilities for the low-pressure phase of ZnGa2Te4 have been determined as well as the equation of state of the low- and high-pressure phases. The reported results are compared with those available in the literature for related compounds. Pressure-induced coordination changes and transition mechanisms are also discussed.
Isolation and characterisation of collagen from elk antler velvet
Authors: Lee Do Hun , Hong Heeok , Lodhi Gaurav , Cheong Sun Hee , Park Pyo Jam , Hu Tiejun , Sangwoo Kim , Moon Sang Ho , Jeon Byong Tae
Published: December 2013

Collagen was extracted from the antler velvet of elk (Cervus elaphus). Two types of collagen were prepared namely, acetic acid-soluble collagen and pepsin-soluble collagen. The electrophoretic patterns of both of the collagens showed that they were heterotrimeric, i.e. they consisted of α1α2α3. The total yield of the collagen obtained from the elk antler velvet was 12.1%. Amino acid analysis of the collagen by high-performance liquid chromatography showed that imino acid content such as that of proline and hydroxyproline was high, which might contribute to better visco-elastic properties. The peptide mapping of the collagens showed their similarity with porcine Type I collagen, thereby suggesting that the primary structure of both collagens is identical to that of porcine skin Type I collagen. The thermal denaturation temperature was 37°C, which is comparable to porcine Type I collagen and may also be as a result of high imino acid content.
Data-poor management of African lion hunting using a relative index of abundance
Authors: Edwards Charles T. T. , Bunnefeld Nils , Balme Guy A. , Milner-Gulland E. J.
Published: December 2013

Significance

Trophy hunting is a useful source of income for conservation. However, it remains contentious, not least because quotas for charismatic species in less-developed countries are often too high, contributing to population decline. The decline of lion populations across Africa continues and is not helped by the unsustainable management of hunting concessions. Best practice rests on the enforcement of a minimum age rule for hunting of males, which allows them to breed before they are killed. However, there is still no reliable method for setting quotas at a sustainable level. In this paper, we present such a method, which makes use of readily available data on the time needed to find and kill a lion, and demonstrate its efficacy through simulation.
Scan statistic-based analysis of exome sequencing data identifies
FAN1
at 15q13.3 as a susceptibility gene for schizophrenia and autism
Authors: Ionita-Laza Iuliana , Xu Bin , Makarov Vlad , Buxbaum Joseph D. , Roos J. Louw , Gogos Joseph A. , Karayiorgou Maria
Published: December 2013

Significance

Schizophrenia and autism are severe, lifelong brain disorders with complex etiology and high prevalence. A strong link has been established between both disorders and de novo copy number variants, but the culprit genes remain unknown. This study uses whole-exome sequencing data and a new statistical method based on detecting clusters of rare disease-associated variants to identify the responsible gene(s) within genomic regions affected by de novo copy number variants. We discovered a new gene on chromosome 15q13.3 [
Fanconi-associated nuclease 1
(
FAN1
)], which contains rare risk variants for both schizophrenia and autism.
FAN1
encodes a DNA repair enzyme, thus implicating abnormalities in DNA repair in the genetic component and as potential drug targets in psychiatric and neurodevelopmental disorders.
The Inter-Sectoral Impact Model Intercomparison Project (ISI–MIP): Project framework
Authors: Warszawski Lila , Frieler Katja , Huber Veronika , Piontek Franziska , Serdeczny Olivia , Schewe Jacob
Published: December 2013

The Inter-Sectoral Impact Model Intercomparison Project offers a framework to compare climate impact projections in different sectors and at different scales. Consistent climate and socio-economic input data provide the basis for a cross-sectoral integration of impact projections. The project is designed to enable quantitative synthesis of climate change impacts at different levels of global warming. This report briefly outlines the objectives and framework of the first, fast-tracked phase of Inter-Sectoral Impact Model Intercomparison Project, based on global impact models, and provides an overview of the participating models, input data, and scenario set-up.
Dynamic control of β1 integrin adhesion by the plexinD1-sema3E axis
Authors: Choi Young I. , Duke-Cohan Jonathan S. , Chen Wei , Liu Baoyu , Rossy Jérémie , Tabarin Thibault , Ju Lining , Gui Jingang , Gaus Katharina , Zhu Cheng , Reinherz Ellis L.
Published: December 2013

Significance

Cell-expressed integrins mediate adhesion with other cells and with extracellular matrix and are essential for embryonic development and for controlling leukocyte migration in later life. Integrin adhesion depends on conformational change leading to activation, although it remains unknown exactly how integrins alter their conformational state and adhesion in response to guidance cues. We show that the guidance molecule plexinD1 controls clustering of integrins in patches on the cell membrane and that the activation state of individual integrins in these patches can be switched off by binding of sema3E to plexinD1. Disruption of this pathway causes abnormal thymocyte adhesion regulation and migration during development, leading to autoimmune phenomena.
De novo selection of oncogenes
Authors: Chacón Kelly M. , Petti Lisa M. , Scheideman Elizabeth H. , Pirazzoli Valentina , Politi Katerina , DiMaio Daniel
Published: December 2013

Significance

Artificial proteins may have improved properties compared with proteins that arose during evolution, but approaches to construct active artificial proteins are cumbersome and often constrained by existing protein structures. Here, we used mouse cells to select proteins that formed tumors from a library of small transmembrane proteins with randomized hydrophobic amino acid sequences. The resulting oncoproteins lack amino acid sequences from any known protein and function by activating a cellular growth factor receptor. This approach can be used to generate structures not observed in nature, create prototypes for research and possibly clinical uses, and provide insight into cell biology, protein–protein interactions, and evolution.
Effective functional maturation of invariant natural killer T cells is constrained by negative selection and T-cell antigen receptor affinity
Authors: Bedel Romain , Berry Richard , Mallevaey Thierry , Matsuda Jennifer L. , Zhang Jingjing , Godfrey Dale I. , Rossjohn Jamie , Kappler John W. , Marrack Philippa , Gapin Laurent
Published: December 2013

Significance

Several different populations of T lymphocytes develop in the thymus from a common precursor. Each population plays a unique and critical role in the mounting and resolution of an immune response. The mechanisms responsible for the emergence of these different populations remain incompletely understood. We demonstrate that strict “Goldilocks” conditions of affinity for self-lipids by the T-cell antigen receptor expressed on T-cell precursors are necessary for imprinting the proper developmental program toward the invariant NK T-cell lineage. Our results establish a direct link between the affinity of the T-cell receptor for self-antigens and the proper development of a unique population of lymphocytes that has been implicated in the modulation of a multitude of immune responses in mice and humans.
Rare event of histone demethylation can initiate singular gene expression of olfactory receptors
Authors: Tan Longzhi , Zong Chenghang , Xie X. Sunney
Published: December 2013

Significance

In mammals, the sense of odors relies on the peculiar expression pattern of olfactory receptors (ORs). Each single neuron chooses one, and only one, from all ∼1,400 OR genes that are present in a mouse genome. In neurobiology, a long-standing mystery is how such singularity can be achieved. We show theoretically that a simple kinetic scheme of OR activation followed by feedback can be solely responsible for the observed singularity, as long as the two timescales—slow activation by epigenetic modification and fast feedback by transcriptional regulation—are well separated. Our work provides the theoretical underpinning behind the choice of ORs, and demonstrates how the nervous system utilizes the kinetics of epigenetic changes to direct neurogenesis.
Local domains of motor cortical activity revealed by fiber-optic calcium recordings in behaving nonhuman primates
Authors: Adelsberger Helmuth , Zainos Antonio , Alvarez Manuel , Romo Ranulfo , Konnerth Arthur
Published: December 2013

Significance

Motor cortex contains a map of the body that is used to control muscles or movements. However, whether movements are controlled by a spatially distributed neuronal circuit or by segregated clusters of neurons is unknown. We combined optic-fiber–based calcium recordings with cortical microstimulation at two well-separated sites of motor cortex in a behaving monkey. We demonstrate that local cortical activity was tightly associated with distinct and stereotypical movements. Increasing stimulation intensity increased both the amplitude of the movements and the level of neuronal activity. Importantly, the activity remained local, without invading the recording domain of the second optical fiber. These results suggest that motor cortex is functionally organized in segregated clusters of neurons that preferentially code specific movements.
Algorithmic framework for X-ray nanocrystallographic reconstruction in the presence of the indexing ambiguity
Authors: Donatelli Jeffrey J. , Sethian James A.
Published: December 2013

Significance

X-ray nanocrystallography is a powerful imaging technique which is able to determine the atomic structure of a macromolecule from a large ensemble of nanocrystals. Determining structure from this ensemble is challenging because the images are noisy, and individual crystal sizes, orientations, and incident photon flux densities are unknown. Additionally, lattice symmetries may lead to orientation ambiguities. Here, we show how to determine crystal size, incident photon flux density, and crystal orientation from noisy data. We also demonstrate that these data can be used to perform reconstruction without extra experimental requirements, atomicity assumptions, or knowledge of similar structures.
Nucleolin is important for Epstein–Barr virus nuclear antigen 1-mediated episome binding, maintenance, and transcription
Authors: Chen Ya-Lin , Liu Cheng-Der , Cheng Chi-Ping , Zhao Bo , Hsu Hao-Jen , Shen Chih-Long , Chiu Shu-Jun , Kieff Elliott , Peng Chih-wen
Published: December 2013

Significance

Epstein–Barr Virus (EBV) genome persistence and expression in human cells can result in human lymphocyte or epithelial cell malignancies. EBV genome persistence and gene expression depends on the EBV encoded Epstein–Barr virus nuclear antigen 1 (EBNA1) protein binding to cognate sites in EBV episomes. Search for a cell protein necessary for EBNA1 interaction with EBV episomes identified a low-level nucleolin (NCL) association with EBNA1. Despite low-level stable association, NCL shRNA knockdowns revealed wild-type NCL, but not an NCL ATP binding site point mutant to be critical for EBNA1 binding to EBV episomes, transcription, and genome maintenance. These experiments identify NCL and NCL K429 as potential targets for inhibition of EBNA1’s role in EBV oncogenesis.
Stuck in stabilisation? South Africa's post-apartheid macro-economic policy between ideological conversion and technocratic capture
Authors: Segatti Aurelia , Pons-Vignon Nicolas
Published: December 2013

This article explores post-apartheid South Africa's commitment to macro-economic orthodoxy. Its key argument is that South Africa offers an exemplary case of neoliberal deepening which has entailed three interconnected processes: ideological conversion, a stated focus on poverty and development covering a deep commitment to orthodox macro policies, entailing institutions and a set of practices, and a far-reaching state restructuring involving the emergence and consolidation of a hegemonic treasury. Drawing on an analysis of grey literature, policy documents and a series of interviews with policy-makers, the article first discusses neoliberalism in South Africa, focusing on the ‘conversion’ of key ANC leaders to neoclassical economic orthodoxy. It then turns to the central, yet under-researched, instrument of neoliberal deepening: the emergence and consolidation of a dominant national treasury with the ability to shape policy-making across all areas of state intervention. The article closes on a call to envisage concurrently ideological conversion and state formation to understand the dynamics of neoliberalism, and its paradoxical resilience in the South Africa case.
Does religiosity determine affinities to CSR?
Authors: Jamali Dima , Sdiani Yusuf
Published: December 2013

This paper aims at exploring the extent to which Corporate Social Responsibility (CSR) orientations are influenced by the level of religiosity among business professionals. Previous empirical research has highlighted the influence of personal values and belief systems on managerial
CSR orientations, presenting mixed evidence in relation to the influence of religious ethics on responsible business orientations. Our paper advances knowledge in this important area of research by (1) synthesizing scattered available literature on the topic and (2) presenting fresh empirical
insights from the Lebanese multi-religious context in relation to how an individual’s type of religiosity (intrinsic/extrinsic) affects their views of CSR. The results suggest that social extrinsic religiosity is related to a broader perspective of CSR, while intrinsic religiosity is
related to a narrow view of CSR. Relevant insights and implications are synthesized accordingly.
Autophagy and metacaspase determine the mode of cell death in plants
Authors: Minina Elena A. , Filonova Lada H. , Fukada Kazutake , Savenkov Eugene I. , Gogvadze Vladimir , Clapham David , Sanchez-Vera Victoria , Suarez Maria F. , Zhivotovsky Boris , Daniel Geoffrey , Smertenko Andrei , Bozhkov Peter V.
Published: December 2013

Although animals eliminate apoptotic cells using macrophages, plants use cell corpses throughout development and disassemble cells in a cell-autonomous manner by vacuolar cell death. During vacuolar cell death, lytic vacuoles gradually engulf and digest the cytoplasmic content. On the other hand, acute stress triggers an alternative cell death, necrosis, which is characterized by mitochondrial dysfunction, early rupture of the plasma membrane, and disordered cell disassembly. How both types of cell death are regulated remains obscure. In this paper, we show that vacuolar death in the embryo suspensor of Norway spruce requires autophagy. In turn, activation of autophagy lies downstream of metacaspase mcII-Pa, a key protease essential for suspensor cell death. Genetic suppression of the metacaspase–autophagy pathway induced a switch from vacuolar to necrotic death, resulting in failure of suspensor differentiation and embryonic arrest. Our results establish metacaspase-dependent autophagy as a bona fide mechanism that is responsible for cell disassembly during vacuolar cell death and for inhibition of necrosis.
Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold
Authors: Cao Xu , Ma Linlin , Yang Fan , Wang KeWei , Zheng Jie
Published: December 2013

Transient receptor potential vanilloid type 1 (TRPV1) channel responds to a wide spectrum of physical and chemical stimuli. In doing so, it serves as a polymodal cellular sensor for temperature change and pain. Many chemicals are known to strongly potentiate TRPV1 activation, though how this is achieved remains unclear. In this study we investigated the molecular mechanism underlying the gating effects of divalent cations Mg2+ and Ba2+. Using a combination of fluorescence imaging and patch-clamp analysis, we found that these cations potentiate TRPV1 gating by most likely promoting the heat activation process. Mg2+ substantially lowers the activation threshold temperature; as a result, a significant fraction of channels are heat-activated at room temperature. Although Mg2+ also potentiates capsaicin- and voltage-dependent activation, these processes were found either to be not required (in the case of capsaicin) or insufficient (in the case of voltage) to mediate the activating effect. In support of a selective effect on heat activation, Mg2+ and Ba2+ cause a Ca2+-independent desensitization that specifically prevents heat-induced channel activation but does not prevent capsaicin-induced activation. These results can be satisfactorily explained within an allosteric gating framework in which divalent cations strongly promote the heat-dependent conformational change or its coupling to channel activation, which is further coupled to the voltage- and capsaicin-dependent processes.
Protonation controls ASIC1a activity via coordinated movements in multiple domains
Authors: Bonifacio Gaetano , Lelli Cláudia Igutti Suenaga , Kellenberger Stephan
Published: December 2013

Acid-sensing ion channels (ASICs) are neuronal Na+-conducting channels activated by extracellular acidification. ASICs are involved in pain sensation, expression of fear, and neurodegeneration after ischemic stroke. Functional ASICs are composed of three identical or homologous subunits, whose extracellular part has a handlike structure. Currently, it is unclear how protonation of residues in extracellular domains controls ASIC activity. Knowledge of these mechanisms would allow a rational development of drugs acting on ASICs. Protonation may induce conformational changes that control the position of the channel gate. We used voltage-clamp fluorometry with fluorophores attached to residues in different domains of ASIC1a to detect conformational changes. Comparison of the timing of fluorescence and current signals identified residues involved in movements that preceded desensitization and may therefore be associated with channel opening or early steps leading to desensitization. Other residues participated in movements intimately linked to desensitization and recovery from desensitization. Fluorescence signals of all mutants were detected at more alkaline pH than ionic currents. Their midpoint of pH dependence was close to that of steady-state desensitization, whereas the steepness of the pH fluorescence relationship was closer to that of current activation. A sequence of movements was observed upon acidification, and its backward movements during recovery from desensitization occurred in the reverse order, indicating that the individual steps are interdependent. Furthermore, the fluorescence signal of some labeled residues in the finger domain was strongly quenched by a Trp residue in the neighboring β-ball domain. Upon channel activation, their fluorescence intensity increased, indicating that the finger moved away from the β ball. This extensive analysis of activity-dependent conformational changes in ASICs sheds new light on the mechanisms by which protonation controls ASIC activity.
Functional reconstitution of the mitochondrial Ca2+/H+ antiporter Letm1
Authors: Tsai Ming-Feng , Jiang Dawei , Zhao Linlin , Clapham David , Miller Christopher
Published: December 2013

The leucine zipper, EF hand–containing transmembrane protein 1 (Letm1) gene encodes a mitochondrial inner membrane protein, whose depletion severely perturbs mitochondrial Ca2+ and K+ homeostasis. Here we expressed, purified, and reconstituted human Letm1 protein in liposomes. Using Ca2+ fluorophore and 45Ca2+-based assays, we demonstrate directly that Letm1 is a Ca2+ transporter, with apparent affinities of cations in the sequence of Ca2+ ≈ Mn2+ > Gd3+ ≈ La3+ > Sr2+ >> Ba2+, Mg2+, K+, Na+. Kinetic analysis yields a Letm1 turnover rate of 2 Ca2+/s and a Km of ∼25 µM. Further experiments show that Letm1 mediates electroneutral 1 Ca2+/2 H+ antiport. Letm1 is insensitive to ruthenium red, an inhibitor of the mitochondrial calcium uniporter, and CGP-37157, an inhibitor of the mitochondrial Na+/Ca2+ exchanger. Functional properties of Letm1 described here are remarkably similar to those of the H+-dependent Ca2+ transport mechanism identified in intact mitochondria.
Foliations on non-metrisable manifolds: Absorption by a Cantor black hole
Authors: Baillif Mathieu , Gabard Alexandre , Gauld David
Published: December 2013

We investigate contrasting behaviours emerging when studying foliations on non-metrisable manifolds.
A hierarchical statistical modeling approach to analyze proteomic isobaric tag for relative and absolute quantitation data
Authors: Zhou Cong , Walker Michael J. , Williamson Andrew J. K. , Pierce Andrew , Berzuini Carlo , Dive Caroline , Whetton Anthony D.
Published: December 2013

Motivation: Isobaric tag for relative and absolute quantitation (iTRAQ) is a widely used method in quantitative proteomics. A robust data analysis strategy is required to determine protein quantification reliability, i.e. changes due to biological regulation rather than technical variation, so that proteins that are differentially expressed can be identified.

Methods: Samples were created by mixing 5, 10, 15 and 20 μg Escherichia coli cell lysate with 100 μg of cell lysate from mouse, corresponding to expected relative fold changes of one for mouse proteins and from 0.25 to 4 for E.coli proteins. Relative quantification was carried out using eight channel isobaric tagging with iTRAQ reagent, and proteins were identified using a TripleTOF 5600 mass spectrometer. Technical variation inherent in this iTRAQ dataset was systematically investigated.

Results: A hierarchical statistical model was developed to use quantitative information at peptide level and protein level simultaneously to estimate variation present in each individual peptide and protein. A novel data analysis strategy for iTRAQ, denoted in short as WHATraq, was subsequently proposed with its performance evaluated by the proportion of E.coli proteins that are successfully identified as differentially expressed. Compared with two benchmark data analysis strategies WHATraq was able to identify at least 62.8% more true positive proteins that are differentially expressed. Further validated using a biological iTRAQ dataset including multiple biological replicates from varied murine cell lines, WHATraq performed consistently and identified 375% more proteins as being differentially expressed among different cell lines than the other data analysis strategies.

Contact:  cdive@picr.man.ac.uk or tony.whetton@manchester.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
SILVER: an efficient tool for stable isotope labeling LC-MS data quantitative analysis with quality control methods
Authors: Chang Cheng , Zhang Jiyang , Han Mingfei , Ma Jie , Zhang Wei , Wu Songfeng , Liu Kehui , Xie Hongwei , He Fuchu , Zhu Yunping
Published: December 2013

Summary: With the advance of experimental technologies, different stable isotope labeling methods have been widely applied to quantitative proteomics. Here, we present an efficient tool named SILVER for processing the stable isotope labeling mass spectrometry data. SILVER implements novel methods for quality control of quantification at spectrum, peptide and protein levels, respectively. Several new quantification confidence filters and indices are used to improve the accuracy of quantification results. The performance of SILVER was verified and compared with MaxQuant and Proteome Discoverer using a large-scale dataset and two standard datasets. The results suggest that SILVER shows high accuracy and robustness while consuming much less processing time. Additionally, SILVER provides user-friendly interfaces for parameter setting, result visualization, manual validation and some useful statistics analyses.

Availability and implementation: SILVER and its source codes are freely available under the GNU General Public License v3.0 at http://bioinfo.hupo.org.cn/silver.

Contact:  zhuyunping@gmail.com, hefc@nic.bmi.ac.cn and xhwei65@163.com

Supplementary information:  Supplementary data are available at Bioinformatics online
Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis
Authors: Brenu Ekua Weba , Huth Teilah K. , Hardcastle Sharni L. , Fuller Kirsty , Kaur Manprit , Johnston Samantha , Ramos Sandra B. , Staines Don R. , Marshall-Gradisnik Sonya M.
Published: December 2013

Perturbations in immune processes are a hallmark of a number of autoimmune and inflammatory disorders. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an inflammatory disorder with possible autoimmune correlates, characterized by reduced NK cell activity, elevations in regulatory T cells (Tregs) and dysregulation in cytokine levels. The purpose of this article is to examine innate and adaptive immune cell phenotypes and functional characteristics that have not been previously examined in CFS/ME patients. Thirty patients with CFS/ME and 25 non-fatigued controls were recruited for this study. Whole blood samples were collected from all participants for the assessment of cell phenotypes, functional properties, receptors, adhesion molecules, antigens and intracellular proteins using flow cytometric protocols. The cells investigated included NK cells, dendritic cells, neutrophils, B cells, T cells, γδT cells and Tregs. Significant changes were observed in B-cell subsets, Tregs, CD4+CD73+CD39+ T cells, cytotoxic activity, granzyme B, neutrophil antigens, TNF-α and IFN-γ in the CFS/ME patients in comparison with the non-fatigued controls. Alterations in B cells, Tregs, NK cells and neutrophils suggest significant impairments in immune regulation in CFS/ME and these may have similarities to a number of autoimmune disorders.
Characterizing the strand-specific distribution of non-CpG methylation in human pluripotent cells
Authors: Guo Weilong , Chung Wen-Yu , Qian Minping , Pellegrini Matteo , Zhang Michael Q.
Published: December 2013

DNA methylation is an important defense and regulatory mechanism. In mammals, most DNA methylation occurs at CpG sites, and asymmetric non-CpG methylation has only been detected at appreciable levels in a few cell types. We are the first to systematically study the strand-specific distribution of non-CpG methylation. With the divide-and-compare strategy, we show that CHG and CHH methylation are not intrinsically different in human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We also find that non-CpG methylation is skewed between the two strands in introns, especially at intron boundaries and in highly expressed genes. Controlling for the proximal sequences of non-CpG sites, we show that the skew of non-CpG methylation in introns is mainly guided by sequence skew. By studying subgroups of transposable elements, we also found that non-CpG methylation is distributed in a strand-specific manner in both short interspersed nuclear elements (SINE) and long interspersed nuclear elements (LINE), but not in long terminal repeats (LTR). Finally, we show that on the antisense strand of Alus, a non-CpG site just downstream of the A-box is highly methylated. Together, the divide-and-compare strategy leads us to identify regions with strand-specific distributions of non-CpG methylation in humans.
Increased Prevalence of Eosinophilic Gastrointestinal Disorders in Pediatric PTEN Hamartoma Tumor Syndromes
Authors: Henderson Carol J. , Ngeow Joanne , Collins Margaret H. , Martin Lisa J. , Putnam Philip E. , Abonia Juan P. , Marsolo Keith , Eng Charis , Rothenberg Marc E.
Published: December 2013

Objectives:

The PTEN hamartoma tumor syndromes (PHTSs) are a collection of disorders caused by germline mutations of the tumor suppressor gene PTEN. Eosinophilic gastrointestinal disorders (EGIDs) are rare diseases characterized by food‐induced, eosinophil‐dominant inflammation in various segments of the gastrointestinal tract. On the basis of our clinical observations of several patients with EGID‐PHTS, we investigated whether there is an association between these 2 disorders.

Methods:

The Cincinnati Children's Hospital Medical Center (CCHMC) Informatics for Integrating Biology and the Bedside (i2b2) warehouse was queried for the years 2007 to 2012 using International Classification of Diseases‐9 codes for PTEN‐related diseases; the results were cross‐referenced with participants enrolled in the Cincinnati Center for Eosinophilic Disorder's EGID database to identify patients with both disorders. In an effort to replicate our findings, the Cleveland Clinic Genomic Medicine Institute PTEN database was queried for cases between 2005 and 2012. Inclusion criteria were age ≤18 years, history of PHTS, and an esophagogastroduodenoscopy (EGD) and/or colonoscopy with at least 1 histologic EGID diagnosis confirmed by a CCHMC pathologist. The Pearson χ2 test was used to determine the odds of EGID enrichment in PHTS.

Results:

Of the 1,058,260 CCHMC distinct patients identified by the i2b2 search, 53 had clinical diagnoses suggestive of PHTS. Thirteen of the 53 had PTEN mutations, with 8 of 13 (62%) having had an EGD and/or colonoscopy. Five of the 8 had confirmed EGID. At the Cleveland Clinic, 3 of 75 patients (3/4 who had EGD and/or colonoscopy) with PHTS had confirmed EGID. CCHMC i2b2 query data showed a substantial enrichment of EGIDs in PHTSs (odds ratio 272; confidence interval 89–831, P < 0.0001). An EGID prevalence estimate from the i2b2 query supported a marked enrichment of EGIDs in PHTSs in the Cleveland Clinic database (P < 0.0001). Among the 8 subjects with EGIDs and PHTSs, the age at EGID and PHTS diagnosis was 7.6 ± 3.2 and 7.9 ± 5.8 years, respectively. Patients with EGID‐PHTS had excess eosinophils in biopsies of the esophagus (75%), stomach (38%), and colon (13%), with a notable presence of eosinophil‐rich gastrointestinal polyposis (88%).

Conclusions:

EGID is a previously unrecognized comorbid disease in pediatric patients with PHTS. These data suggest a potential role of PTEN in contributing to EGID susceptibility.
Maternal–Fetal Transmission of Hepatitis C Infection
Authors: Wen Jessica W. , Haber Barbara A.
Published: December 2013

Children with hepatitis C virus infection often differ from adults regarding the rate of viral clearance, duration of infection, and the progression to cirrhosis. In the pediatric population, vertical transmission of hepatitis C virus infection from mother to infant is the most common route of infection. In the present review, we explore the factors that may influence the natural history of hepatitis C virus infection in children who acquire the infection through maternal–fetal transmission. There is particular focus on how viral diversity and the infant immune system may affect viral transmission. An enhanced understanding of maternal–fetal transmission of hepatitis C virus infection has the potential to affect effective drug and vaccine development for both children and adults.
Does Calretinin Immunohistochemistry Reduce Inconclusive Diagnosis in Rectal Biopsies for Hirschsprung Disease?
Authors: de Arruda Lourenção Pedro L.T. , Takegawa Bonifácio K. , Ortolan Erika V.P. , Terra Simone A. , Rodrigues Maria A.M.
Published: December 2013

Many difficulties occur during the evaluation of rectal biopsies for the diagnosis of Hirschsprung disease. We investigated whether the introduction of calretinin (CR) immunohistochemistry in a diagnostic panel could decrease the rate of inconclusive results. Data from 82 patients undergoing rectal biopsies before and after CR introduction were analyzed. Inconclusive results were obtained in 17 of 45 rectal biopsies (37.8%) in the series of cases before CR introduction and in 5 of 42 rectal biopsies (11.9%) in the series of cases after CR (P < 0.006). The inclusion of CR in the histopathologic panel may improve the diagnostic accuracy of Hirschsprung disease.
Energy Requirements for Maintenance and Growth in 3‐ to 4‐Year‐Olds May Be Overestimated by Existing Equations
Authors: Sijtsma Anna , Corpeleijn Eva , Sauer Pieter J.J.
Published: December 2013

Objectives:

To give appropriate dietary advice to preschool children, an estimation of their energy requirements for both maintenance and activity is needed. We compared energy requirements for maintenance, measured by indirect calorimetry against existing equations predicting these requirements in 3‐ to 4‐year‐old children.

Methods:

In 30 children (age 3.4 ± 0.3) from the GECKO Drenthe cohort, height, weight, evening sleeping metabolic rate (SMR) (by indirect calorimetry), fat mass (FM), and fat‐free mass (FFM) (by isotope dilution) were measured. For 25 children, a valid evening SMR was available as a measure for energy used for maintenance and growth. This SMR was compared with existing equations (Schofield, FAO/WHO/UNU, Oxford and Harris‐Benedict). Correlations among SMR and weight, height, FM, and FFM were also calculated.

Results:

From the existing equations, significant higher values, ranging from 58 to 144 kcal/day, were calculated for the BMR compared with the measured SMR results, indicating 8% to 19% overestimation. This overestimation is higher at lower ranges of energy requirement. SMR was positively related to weight (r = 0.488, P = 0.013), height (r = 0.499, P = 0.011), and FFM (r = 0.482, P = 0.027), but not to FM (r = 0.211, P = 0.358).

Conclusions:

Existing equations show higher values for the energy used for maintenance in young children compared to the results of our measurements of the SMR. Energy used for maintenance is correlated with FFM and not with FM.
Remarks on the boundary set of spectral equipartitions
Authors: Bérard P. , Helffer B.
Published: December 2013

Given a bounded open set in

(or in a Riemannian manifold), and a partition of
Ω
by
k
open sets
ω

j

, we consider the quantity

, where
λ
(
ω

j

) is the ground state energy of the Dirichlet realization of the Laplacian in
ω

j

. We denote by ℒ

k

(
Ω
) the infimum of

over all
k
-partitions. A minimal
k
-partition is a partition that realizes the infimum. Although the analysis of minimal
k
-partitions is rather standard when
k
=2 (we find the nodal domains of a second eigenfunction), the analysis for higher values of
k
becomes non-trivial and quite interesting. Minimal partitions are in particular spectral equipartitions, i.e. the ground state energies
λ
(
ω

j

) are all equal. The purpose of this paper is to revisit various properties of nodal sets, and to explore if they are also true for minimal partitions, or more generally for spectral equipartitions. We prove a lower bound for the length of the boundary set of a partition in the two-dimensional situation. We consider estimates involving the cardinality of the partition.
Freezing transitions and extreme values: random matrix theory, and disordered landscapes
Authors: Fyodorov Yan V. , Keating Jonathan P.
Published: December 2013

We argue that thefreezing transition scenario, previously conjectured to occur in the statistical mechanics of 1/f-noise random energy models, governs, after reinterpretation, the value distribution of the maximum of the modulus of the characteristic polynomialspN(θ) of largeN×Nrandom unitary (circular unitary ensemble) matricesUN; i.e. the extreme value statistics ofpN(θ) when. In addition, we argue that it leads to multi-fractal-like behaviour in the total lengthμN(x) of the intervals in which |pN(θ)|>Nx,x>0, in the same limit. We speculate that our results extend to the large values taken by the Riemann zeta functionζ(s) over stretches of the critical lineof given constant length and present the results of numerical computations of the large values of). Our main purpose is to draw attention to the unexpected connections between these different extreme value problems.
Spectral statistics of permutation matrices
Authors: Oren Idan , Smilansky Uzy
Published: December 2013

We compute the mean two-point spectral form factor and the spectral number variance for permutation matrices of large order. The two-point correlation function is expressed in terms of generalized divisor functions, which are frequently discussed in number theory. Using classical results from number theory and casting them in a convenient form, we derive expressions which include the leading and next to leading terms in the asymptotic expansion, thus providing a new point of view on the subject, and improving some known results.
Quantum chaos for point scatterers on flat tori
Authors: Ueberschär Henrik
Published: December 2013

This survey article deals with a delta potential—also known as a point scatterer—on flat two- and three-dimensional tori. We introduce the main conjectures regarding the spectral and wave function statistics of this model in the so-called weak and strong coupling regimes. We report on recent progress as well as a number of open problems in this field.
Quantum ergodicity of random orthonormal bases of spaces of high dimension
Authors: Zelditch Steve
Published: December 2013

We consider a sequenceof finite-dimensional Hilbert spaces of dimensions. Motivating examples are eigenspaces, or spaces of quasi-modes, for a Laplace or Schrödinger operator on a compact Riemannian manifold. The set of Hermitian orthonormal bases ofmay be identified withU(dN), and a random orthonormal basis ofis a choice of a random sequenceUN∈U(dN) from the product of normalized Haar measures. We prove that ifand iftends to a unique limit stateω(A), then almost surely an orthonormal basis is quantum ergodic with limit stateω(A). This generalizes an earlier result of the author in the case whereis the space of spherical harmonics onS2. In particular, it holds on the flat torusifd≥5 and shows that a highly localized orthonormal basis can be synthesized from quantum ergodic ones and vice versa in relatively small dimensions.
Remarks on nodal volume statistics for regular and chaotic wave functions in various dimensions
Authors: Gnutzmann Sven , Lois Stylianos
Published: December 2013

We discuss the statistical properties of the volume of the nodal set of wave functions for two paradigmatic model systems which we consider in arbitrary dimension
s
≥2: the cuboid as a paradigm for a regular shape with separable wave functions and planar random waves as an established model for chaotic wave functions in irregular shapes. We give explicit results for the mean and variance of the nodal volume in the arbitrary dimension, and for their limiting distribution. For the mean nodal volume, we calculate the effect of the boundary of the cuboid where Dirichlet boundary conditions reduce the nodal volume compared with the bulk. Boundary effects for chaotic wave functions are calculated using random waves which satisfy a Dirichlet boundary condition on a hyperplane. We put forward several conjectures on what properties of cuboids generalize to general regular shapes with separable wave functions and what properties of random waves can be expected for general irregular shapes. These universal features clearly distinguish between the two cases.
Cyclobacterium halophilum sp. nov., a marine bacterium isolated from a coastal-marine wetland
Authors: Shahinpei Azadeh , Amoozegar Mohammad Ali , Sepahy Abbas Akhavan , Schumann Peter , Ventosa Antonio
Published: December 2013

A novel Gram-stain-negative, slightly halophilic bacterium, designated strain GASx41T, was isolated from soil of the coastal–marine wetland Gomishan in Iran. Cells of strain GASx41T were curved, ring-like or horseshoe-shaped rods and non-motile. Strain GASx41T was strictly aerobic, and catalase- and oxidase-positive. The strain was able to grow at NaCl concentrations of 1–10 % (w/v), with optimum growth occurring at 2.5–3 % (w/v) NaCl. The optimum temperature and pH for growth were 25–30 °C and pH 7.5–8.0. On the basis of 16S rRNA gene sequence analysis, strain GASx41T was shown to belong to the genus

Cyclobacterium

within the phylum

Bacteroidetes

and showed closest phylogenetic similarity to ‘Cyclobacterium jeungdonense’ HMD3055 (98.0 %). The DNA G+C content of strain GASx41T was 48.1 mol%. The major cellular fatty acids of strain GASx41T were iso-C15 : 0, summed feature 4 (iso-C15 : 0 2-OH and/or C16 : 1ω7c), anteiso-C15 : 0 2-OH, anteiso-C15 : 0 and iso-C17 : 0 3-OH, and its polar lipid pattern consisted of phosphatidylethanolamine, phosphatidylcholine and 12 unknown lipids. The only quinone present was menaquinone 7 (MK-7). All these features confirmed the placement of isolate GASx41T within the genus

Cyclobacterium

. On the basis of evidence from this study, a novel species of the genus

Cyclobacterium

, Cyclobacterium halophilum sp. nov., is proposed, with strain GASx41T ( = IBRC-M 10761T = CECT 8341T) as the type strain.
Enterococcus xiangfangensis sp. nov., isolated from Chinese pickle
Authors: Li Chun Yan , Tian Fen , Zhao Ya Dong , Gu Chun Tao
Published: December 2013

A Gram-stain-positive bacterial strain, 11097T, was isolated from traditional pickle in Heilongjiang Province, China. The bacterium was characterized using a polyphasic approach, including 16S rRNA gene sequence analysis, phenylalanyl-tRNA synthase (pheS) gene sequence analysis, RNA polymerase α subunit (rpoA) gene sequence analysis, fatty acid methyl ester (FAME) analysis, determination of DNA G+C content, DNA–DNA hybridization and an analysis of phenotypic features. Strain 11097T was phylogenetically related to

Enterococcus devriesei

,

E. pseudoavium

,

E. viikkiensis

,

E. avium

,

E. malodoratus

,

E. gilvus

and

E. raffinosus

. Strain 11097T had 99.1–99.9 % 16S rRNA gene sequence similarities, 78.2–83.2 % pheS gene sequence similarities and 93.8–96.6 % rpoA gene sequence similarities with type strains of phylogenetically related species. Based upon polyphasic characterization data obtained in the present study, a novel species of the genus

Enterococcus

, Enterococcus xiangfangensis sp. nov., is proposed with the type strain 11097T ( = LMG 27495T = NCIMB 14834T).
Rhodovulum salis sp. nov. and Rhodovulum viride sp. nov., phototrophic Alphaproteobacteria isolated from marine habitats
Authors: Srinivas A. , Kumar B. Vinay , Sree B. Divya , Tushar L. , Sasikala Ch. , Ramana Ch. V.
Published: December 2013

Two strains (JA746T and JA756T) having yellowish brown-to-green pigment were isolated from a solar saltern and a pink pond, respectively. While both strains were non-motile and shared the presence of bacteriochlorophyll-a, major cellular fatty acids (C18 : 1ω7c, C16 : 0, C18 : 0), quinone (Q-10), polar lipids and hopanoids, they differed from each other in their carotenoid composition. The G+C content of genomic DNA of strains JA746T and 756T was 62.4 and 63.3 mol%, respectively. The 16S rRNA gene-based EzTaxon-e blast search analysis of strains JA746T and 756T indicated highest sequence similarity with members of the genus

Rhodovulum

in the family

Rhodobacteraceae

of the class

Alphaproteobacteria

. Strain JA746T has high sequence similarities with

Rhodovulum visakhapatnamense

JA181T (97.3 %),

Rhodovulum steppense

A-20sT (97.3 %),

Rhodovulum phaeolacus

JA580T (97 %),

Rhodovulum strictum

MB-G2T (97 %) and other members of the genus

Rhodovulum

(<97 %). Strain JA756T has high sequence similarities with

Rhodovulum visakhapatnamense

JA181T (99.8 %),

Rhodovulum sulfidophilum

Hansen W4T (99.1 %),

Rhodovulum kholense

JA297T (97.9 %) and other members of the genus

Rhodovulum

(<97 %). The sequence similarity between strains JA746T and JA756T was 97.5 %. However, these strains are not closely related to each other or to their phylogenetic neighbours since the DNA–DNA reassociation values were less than 56 %. The genomic information was also supported by phenotypic and chemotaxonomic results, leading us to classify strains JA746T ( = NBRC 108898T = KCTC 15180T) and JA756T ( = NBRC 109122T = KCTC 15223T) as the type strains of two novel species of the genus

Rhodovulum

, for which the names

Rhodovulum

salis sp. nov. and

Rhodovulum

viride sp. nov. are proposed, respectively.
Molecular epidemiology of Clostridium difficile in a tertiary hospital of China
Authors: Chen Yun-Bo , Gu Si-Lan , Wei Ze-Qing , Shen Ping , Kong Hai-Sheng , Yang Qing , Li Lan-Juan
Published: December 2013

Clostridium difficile infection (CDI) is caused by toxin-producing strains. It accounts for 20–30 % of antibiotic-associated diarrhoea and particularly accounts for 90 % of pseudomembranous colitis. The epidemiological study of C. difficile is thus important. In this study, we report the molecular epidemiology and ward distribution of C. difficile in a tertiary hospital of China. A total of 161 toxigenic strains were isolated from 1845 patients originating from different wards and the strains were characterized based on toxin profile and multilocus sequence typing. Variable isolation rates were observed in different wards and the occurrence was higher in intensive care unit and geriatric wards. Toxin gene profiling revealed that, out of the 161 isolates, 134 (83.2)% were positive for both toxin A (tcdA) and toxin B (tcdB) (A+B+) followed by toxin A-negative and B-positive (A−B+) (16.8 %) isolates. However, only three of the toxigenic strains (1.9 %) were positive for both the cdtA and cdtB genes. Based on the molecular epidemiology study, a total of 30 different sequence types (STs), including one new ST (ST-220), were distinguishable. ST-54 was the most prevalent (23.0 %), followed by ST-35 (19.3 %) and ST-37 (10.0 %). None of the isolates belonged to ST-1 (ribotype 027) or ST-11 (ribotype 078). Taken together, the toxin profile and the molecular epidemiological data showed that all the ST-37 clades were of toxin type A−B+, which accounted for 59.3 % of all type A−B+ isolates. Meanwhile the clade 1 genotype, ST-54, was widely distributed among the geriatric, infection and haematology wards. There was no outbreak of C. difficile infection during our study; however the possibility of prolonged outbreaks cannot be completely ignored.