bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermodynamics of formation of coffinite, USiO
4
Authors: Guo Xiaofeng , Szenknect Stéphanie , Mesbah Adel , Labs Sabrina , Clavier Nicolas , Poinssot Christophe , Ushakov Sergey V. , Curtius Hildegard , Bosbach Dirk , Ewing Rodney C. , Burns Peter C. , Dacheux Nicolas , Navrotsky Alexandra
Published: May 2015

Significance

Coffinite, USiO
4
, is an important alteration mineral of uraninite. Its somewhat unexpected formation and persistence in a large variety of natural and contaminated low-temperature aqueous settings must be governed by its thermodynamic properties, which, at present, are poorly constrained. We report direct calorimetric measurements of the enthalpy of formation of coffinite. The calorimetric data confirm the thermodynamic metastability of coffinite with respect to uraninite plus quartz but show that it can form from silica-rich aqueous solutions in contact with dissolved uranium species in a reducing environment. These constraints on thermodynamic properties support that coffinitization in uranium deposits and spent nuclear fuel occurs through dissolution of UO
2
(often forming hexavalent uranium intermediates) followed by reaction with silica-rich fluids.
Protective effects of Nitraria retusa extract and its constituent isorhamnetin against amyloid β-induced cytotoxicity and amyloid β aggregation
Authors: Iida Akihisa , Usui Takeo , Zar Kalai Feten , Han Junkyu , Isoda Hiroko , Nagumo Yoko
Published: May 2015

Nitraria retusa is a halophyte species that is distributed in North Africa and used as a traditional medicinal plant. In this study, N. retusa ethanol extract and its constituent isorhamnetin (IRA) protected against amyloid β (Aβ)-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. An in vitro Aβ aggregation assay suggested that IRA destabilizes Aβ fibrils.
Profilin 2 promotes migration, invasion, and stemness of HT29 human colorectal cancer stem cells
Authors: Kim Min-Jung , Lee Yoo-Sun , Han Gi-Yeon , Lee Han-Na , Ahn Chiyoung , Kim Chan-Wha
Published: May 2015

We investigated the role of profilin 2 in the stemness, migration, and invasion of HT29 cancer stem cells (CSCs). Increased and decreased levels of profilin 2 significantly enhanced and suppressed the self-renewal, migration, and invasion ability of HT29 CSCs, respectively. Moreover, profilin 2 directly regulated the expression of stemness markers (CD133, SOX2, and β-catenin) and epithelial mesenchymal transition (EMT) markers (E-cadherin and snail). CD133 and β-catenin were up-regulated by overexpression of profilin 2 and down-regulated by depletion of profilin 2. SOX2 was decreased by profilin 2 depletion. E-cadherin was not influenced by profilin 2- overexpression but increased by profilin 2- knockdown. The expression of snail was suppressed by profilin 2- knockdown. We speculated that stemness and the EMT are closely linked through profilin 2-related pathways. Therefore, this study indicates that profilin 2 affects the metastatic potential and stemness of colorectal CSCs by regulating EMT- and stemness-related proteins.
Vibrotactile timing: Are vibrotactile judgements of duration affected by repetitive stimulation?
Authors: Jones Luke A. , Ogden Ruth S.
Published: May 2015

Timing in the vibrotactile modality was explored. Previous research has shown that repetitive auditory stimulation (in the form of click-trains) and visual stimulation (in the form of flickers) can alter duration judgements in a manner consistent with a “speeding up” of an internal clock. In Experiments 1 and 2 we investigated whether repetitive vibrotactile stimulation in the form of vibration trains would also alter duration judgements of either vibrotactile stimuli or visual stimuli. Participants gave verbal estimates of the duration of vibrotactile and visual stimuli that were preceded either by five seconds of 5-Hz vibration trains, or, by a five-second period of no vibrotactile stimulation, the end of which was signalled by a single vibration pulse (control condition). The results showed that durations were overestimated in the vibrotactile train conditions relative to the control condition; however, the effects were not multiplicative (did not increase with increasing stimulus duration) and as such were not consistent with a speeding up of the internal clock, but rather with an additive attentional effect. An additional finding was that the slope of the vibrotactile psychometric (control condition) function was not significantly different from that of the visual (control condition) function, which replicates a finding from a previous cross-modal comparison of timing.
The transcription factor Bcl11b is specifically expressed in group 2 innate lymphoid cells and is essential for their development
Authors: Yu Yong , Wang Cui , Clare Simon , Wang Juexuan , Lee Song-Choon , Brandt Cordelia , Burke Shannon , Lu Liming , He Daqian , Jenkins Nancy A. , Copeland Neal G. , Dougan Gordon , Liu Pentao
Published: May 2015

Group 2 innate lymphoid cells (ILCs), or ILC2s, are a subset of recently identified ILCs, which play important roles in innate immunity by producing type 2 effector cytokines. Several transcription factors have been found to have critical functions in the development of both ILC2s and T cells. We report here that Bcl11b, a transcription factor essential in T cell lineage commitment and maintenance, is specifically expressed in progenitors committed to the ILC2 lineage and is required for ILC2 development. The Bcl11b gene is expressed in ∼28% of ILC progenitors (ILCPs; common helper innate lymphoid progenitors or ILCPs expressing either ID2 or promyelocytic leukemia zinc finger, respectively). Both in vitro and in vivo, these Bcl11b-expressing early ILCPs generate only ILC2s. Inactivation of Bcl11b causes a complete loss of ILC2 development from hematopoietic progenitors, which is confirmed upon immune challenge with either papain administration or influenza virus infection.
Glycine-dependent activation of NMDA receptors
Authors: Cummings Kirstie A. , Popescu Gabriela K.
Published: May 2015

N-methyl-d-aspartate (NMDA) receptors are the only neurotransmitter receptors whose activation requires two distinct agonists. Heterotetramers of two GluN1 and two GluN2 subunits, NMDA receptors are broadly distributed in the central nervous system, where they mediate excitatory currents in response to synaptic glutamate release. Pore opening depends on the concurrent presence of glycine, which modulates the amplitude and time course of the glutamate-elicited response. Gating schemes for fully glutamate- and glycine-bound NMDA receptors have been described in sufficient detail to bridge the gap between microscopic and macroscopic receptor behaviors; for several receptor isoforms, these schemes include glutamate-binding steps. We examined currents recorded from cell-attached patches containing one GluN1/GluN2A receptor in the presence of several glycine-site agonists and used kinetic modeling of these data to develop reaction schemes that include explicit glycine-binding steps. Based on the ability to match a series of experimentally observed macroscopic behaviors, we propose a model for activation of the glutamate-bound NMDA receptor by glycine that predicts apparent negative agonist cooperativity and glycine-dependent desensitization in the absence of changes in microscopic binding or desensitization rate constants. These results complete the basic steps of an NMDA receptor reaction scheme for the GluN1/GluN2A isoform and prompt a reevaluation of how glycine controls NMDA receptor activation. We anticipate that our model will provide a useful quantitative instrument to further probe mechanisms and structure–function relationships of NMDA receptors and to better understand the physiological and pathological implications of endogenous fluctuations in extracellular glycine concentrations.
Construction of Soliton-Cnoidal Wave Interaction Solution for the (2+1)-Dimensional Breaking Soliton Equation*
Authors: Cheng Wen-Guang , Li Biao , Chen Yong
Published: May 2015

In this paper, the truncated Painlevé analysis and the consistent tanh expansion (CTE) method are developed for the (2+1)-dimensional breaking soliton equation. As a result, the soliton-cnoidal wave interaction solution of the equation is explicitly given, which is difficult to be found by other traditional methods. When the value of the Jacobi elliptic function modulus m = 1, the soliton-cnoidal wave interaction solution reduces back to the two-soliton solution. The method can also be extended to other types of nonlinear evolution equations in mathematical physics.
An Alternative Adiabatic Quantum Algorithm for the Hamiltonian Cycle Problem
Authors: Zhang Da-Jian , Tong Dian-Min , Lu Yao , Long Gui-Lu
Published: May 2015

We put forward an alternative quantum algorithm for finding Hamiltonian cycles in any N-vertex graph based on adiabatic quantum computing. With a von Neumann measurement on the final state, one may determine whether there is a Hamiltonian cycle in the graph and pick out a cycle if there is any. Although the proposed algorithm provides a quadratic speedup, it gives an alternative algorithm based on adiabatic quantum computation, which is of interest because of its inherent robustness.
Vector Meson Mass in Finite Density and Temperature Lattice QCD*
Authors: Wang Rui , Chen Ying , Gong Ming , Liu Chuan , Liu Yu-Bin , Liu Zhao-Feng , Ma Jian-Ping , Meng Xiang-Fei , Zhang Jian-Bo
Published: May 2015

Vector meson mass values are studied at finite chemical potential and temperature in lattice QCD with lattice size of 24 × 122 × 6 using two flavors of staggered quarks. The investigation focuses on the change of the vector meson mass in the critical region close to Tc with two different types of chemical potentials switched on: the isoscalar chemical potential μs and its isovector counterpart μv. It is found that the vector meson mass increases in the QGP phase with both chemical potentials and decreases with μs in the confinement phase.
Asymmetric Coupling in Two-Lane Asymmetric Simple Exclusion Processes with Unequal Injection Rates: Effect of Different Hoping Rates*
Authors: Xiao Song , Chen Xiao-Yu , Liu Yan-Na
Published: May 2015

This paper investigates the effect of both unequal injection rates and different hopping rates on two-lane asymmetric simple exclusion processes (ASEPs) with asymmetric coupling. When the hopping rates of both lanes are different, the system includes six steady phases, however, when the hopping rates of both lanes are same, the seventh phase (MC, MC) will exist in the system. Interestingly, with different hopping rates of both lanes, the densities of the system cannot be influenced by the non-zero vertical transition rate. Our theoretical arguments are in well agreement with extensively performed Monte Carlo simulations.
Molecular Dynamics Studies on Ballistic Thermal Resistance of Graphene Nano-Junctions*
Authors: Yao Wen-Jun , Cao Bing-Yang
Published: May 2015

Ballistic thermal resistance of graphene nano-junctions is investigated using non-equilibrium molecular dynamics simulation. The simulation system is consisted of two symmetrical trapezoidal or rectangular graphene nano-ribbons (GNRs) and a connecting nanoscale constriction in between. From the simulated temperature profile, a big temperature jump resulted from the constriction is found, which is proportional to the heat current and corresponds to a local ballistic thermal resistance. Fixing the constriction width and the length of GNRs, this ballistic thermal resistance is independent of the width of the GNRs bottom layer, i.e., the convex angle. But interestingly, this thermal resistance has obvious size effect. It is inversely proportional to the constriction width and will disappear with the constriction being wider. Moreover, based on the phonon dynamics theory, a theoretical model of the ballistic thermal resistance in two-dimensional nano-systems is developed, which gives a good explanation on microcosmic level and agrees well with the simulation result quantitatively and qualitatively.
PsyGeNET: a knowledge platform on psychiatric disorders and their genes
Authors: Gutiérrez-Sacristán Alba , Grosdidier Solène , Valverde Olga , Torrens Marta , Bravo Àlex , Piñero Janet , Sanz Ferran , Furlong Laura I.
Published: May 2015

Summary: PsyGeNET (Psychiatric disorders and Genes association NETwork) is a knowledge platform for the exploratory analysis of psychiatric diseases and their associated genes. PsyGeNET is composed of a database and a web interface supporting data search, visualization, filtering and sharing. PsyGeNET integrates information from DisGeNET and data extracted from the literature by text mining, which has been curated by domain experts. It currently contains 2642 associations between 1271 genes and 37 psychiatric disease concepts. In its first release, PsyGeNET is focused on three psychiatric disorders: major depression, alcohol and cocaine use disorders. PsyGeNET represents a comprehensive, open access resource for the analysis of the molecular mechanisms underpinning psychiatric disorders and their comorbidities.

Availability and implementation: The PysGeNET platform is freely available at http://www.psygenet.org/. The PsyGeNET database is made available under the Open Database License (http://opendatacommons.org/licenses/odbl/1.0/).

Contact:  lfurlong@imim.es

Supplementary information: Supplementary data are available at Bioinformatics online.
International collaboration and science in China: a Western perspective
Authors: Qiu Jane
Published: May 2015

As China is making great strides in economic development and innovative capacity, it has become an increasingly important player in major international scientific projects. But its role largely depends on the areas of research and can vary greatly—from being mainly a supplier of raw data to having genuine intellectual input. Last year, a panel of Chinese scientists had a heated debate over how China can get the most out of international collaboration, what government's role should be, and how Chinese scientists could go beyond the mainstream science (National Science Review 2014, 1: 318–21). In the second of a series of forums organized by NSR on the topic, its executive associate editor Mu-ming Poo discusses these issues with four leading scientists in Europe and the United States.

Jeremy Farrar

An expert on infectious diseases and Director of the Wellcome Trust in London, UK

Harrald Fuchs

Material scientist at the University Münster and Director of the Center for Nanotechnology (CeNTech), Germany

Jian Lin

Marine geophysicist at the Woods Hole Oceanographic Institution in Massachusetts, USA

Christopher White

Particle physicist and Vice Provost for academic affairs at the Illinois Institute of Technology, USA

Mu-ming Poo (Chair)

Neuroscientist and Director of the Institute of Neurosciences, Chinese Academy of Sciences, in Shanghai
The impact of maternal infection with
Mycobacterium tuberculosis
on the infant response to bacille Calmette–Guérin immunization
Authors: Mawa Patrice A. , Nkurunungi Gyaviira , Egesa Moses , Webb Emily L. , Smith Steven G. , Kizindo Robert , Akello Mirriam , Lule Swaib A. , Muwanga Moses , Dockrell Hazel M. , Cose Stephen , Elliott Alison M.
Published: May 2015

Bacille Calmette–Guérin (BCG) immunization provides variable protection against tuberculosis. Prenatal antigen exposure may have lifelong effects on responses to related antigens and pathogens. We therefore hypothesized that maternal latent
Mycobacterium tuberculosis
infection (LTBI) influences infant responses to BCG immunization at birth. We measured antibody (
n
= 53) and cellular (
n
= 31) responses to
M. tuberculosis
purified protein derivative (PPD) in infants of mothers with and without LTBI, in cord blood and at one and six weeks after BCG. The concentrations of PPD-specific antibodies declined between birth (median [interquartile range (IQR)]) 5600 ng ml
−1
[3300–11 050] in cord blood) and six weeks (0.00 ng ml
−1
[0–288]). Frequencies of PPD-specific IFN-γ-expressing CD4
+
T cells increased at one week and declined between one and six weeks (
p
= 0.031). Frequencies of IL-2- and TNF-α-expressing PPD-specific CD4
+
T cells increased between one and six weeks (
p
= 0.019,
p
= 0.009, respectively). At one week, the frequency of PPD-specific CD4
+
T cells expressing any of the three cytokines, combined, was lower among infants of mothers with LTBI, in crude analyses (
p
= 0.002) and after adjusting for confounders (mean difference, 95% CI −0.041% (−0.082, −0.001)). In conclusion, maternal LTBI was associated with lower infant anti-mycobacterial T-cell responses immediately following BCG immunization. These findings are being explored further in a larger study.
Can immunological principles and cross-disciplinary science illuminate the path to vaccines for HIV and other global health challenges?
Authors: Wilson Christopher B. , Karp Christopher L.
Published: May 2015

Vaccines are one of the most impactful and cost-effective public health measures of the twentieth century. However, there remain great unmet needs to develop vaccines for globally burdensome infectious diseases and to allow more timely responses to emerging infectious disease threats. Recent advances in the understanding of immunological principles operative not just in model systems but in humans in concert with the development and application of powerful new tools for profiling human immune responses, in our understanding of pathogen variation and evolution, and in the elucidation of the structural aspects of antibody–pathogen interactions, have illuminated pathways by which these unmet needs might be addressed. Using these advances as foundation, we herein present a conceptual framework by which the discovery, development and iterative improvement of effective vaccines for HIV, malaria and other globally important infectious diseases might be accelerated.
Searching for the human genetic factors standing in the way of universally effective vaccines
Authors: Mentzer Alexander J. , O'Connor Daniel , Pollard Andrew J. , Hill Adrian V. S.
Published: May 2015

Vaccines have revolutionized modern public health. The effectiveness of some vaccines is limited by the variation in response observed between individuals and across populations. There is compelling evidence that a significant proportion of this variability can be attributed to human genetic variation, especially for those vaccines administered in early life. Identifying and understanding the determinants of this variation could have a far-reaching influence upon future methods of vaccine design and deployment. In this review, we summarize the genetic studies that have been undertaken attempting to identify the genetic determinants of response heterogeneity for the vaccines against hepatitis B, measles and rubella. We offer a critical appraisal of these studies and make a series of suggestions about how modern genetic techniques, including genome-wide association studies, could be used to characterize the genetic architecture of vaccine response heterogeneity. We conclude by suggesting how the findings from such studies could be translated to improve vaccine effectiveness and target vaccination in a more cost-effective manner.
Vibrio salilacus sp. nov., a new member of the Anguillarum clade with six alleles of the 16S rRNA gene from a saline lake
Authors: Zhong Zhi-Ping , Liu Ying , Liu Hong-Can , Wang Fang , Zhou Yu-Guang , Liu Zhi-Pei
Published: May 2015

A Gram-stain-negative, catalase- and oxidase-positive, facultatively aerobic bacterium, strain DSG-S6T, was isolated from Dasugan Lake (salinity 3.1 %, w/w), China. Its taxonomic position was determined by using a polyphasic approach. Cells of strain DSG-S6T were non-spore-forming, slightly bent rods, and motile by means of a single polar flagellum. Growth occurred in the presence of 0–7.0  % (w/v) NaCl (optimum, 2.0  %), at 4–35 °C (optimum, 30 °C) and at pH 6.0–10.5 (optimum, pH 8.0–8.5). C16 : 0, C18 : 1ω7c and C16 : 1ω7c and/or C16 : 1ω6c were the major fatty acids. Six alleles of the 16S rRNA gene sharing 98.9–99.9  % similarity were detected in strain DSG-S6T, which showed highest 16S rRNA gene sequence similarity to Vibrio aestuarianus ATCC 35048T (97.7  %), then to Vibrio pacinii LMG 19999T (97.6  %) and Vibrio metschnikovii CIP 69.14T (96.8  %). Multilocus sequence analysis of four housekeeping genes and 16S rRNA genes clearly clustered it as a member of the Anguillarum clade. Mean DNA–DNA relatedness between strain DSG-S6T and V. aestuarianus NBRC 15629T, V. pacinii CGMCC 1.12557T and V. metschnikovii JCM 21189T was 20.6 ± 2.3, 38.1 ± 3.5 and 24.2 ± 2.8  %, respectively. The DNA G+C content was 46.8 mol% (T
m). Based on the data, it is concluded that strain DSG-S6T represents a novel species of the genus Vibrio, for which the name Vibrio salilacus sp. nov. is proposed. The type strain is DSG-S6T ( = CGMCC 1.12427T = JCM 19265T).
Sphingomicrobium aestuariivivum sp. nov., isolated from a tidal flat
Authors: Park Sooyeon , Park Ji-Min , Sun Joo Eun , Won Sung-Min , Kyum Kim Myung , Yoon Jung-Hoon
Published: May 2015

A Gram-stain-negative, aerobic, non-spore-forming, non-flagellated and coccoid, ovoid or rod-shaped bacterial strain, designated AH-M8T, was isolated from a tidal flat sediment collected from Aphae Island in the south-western sea, South Korea. Strain AH-M8T grew optimally at 35 °C, at pH 7.0–8.0 and in the presence of 2.0–3.0  % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain AH-M8T belonged to the genus Sphingomicrobium, clustering with the type strain of Sphingomicrobium astaxanthinifaciens, with which it shared 99.0 % 16S rRNA gene sequence similarity. Sequence similarities to the type strains of other species of the genus Sphingomicrobium were 95.4–96.0  %. Strain AH-M8T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0 as the major fatty acids. The major polar lipids of strain AH-M8T were phosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipid and one unidentified glycolipid. The major polyamine is triamine sym-homospermidine. The DNA G+C content of strain AH-M8T was 66.7 mol% and its mean DNA–DNA relatedness value with S. astaxanthinifaciens JCM 18551T was 21  %. The differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, revealed that strain AH-M8T is separated from other species of the genus Sphingomicrobium. On the basis of the data presented, strain AH-M8T is considered to represent a novel species of the genus Sphingomicrobium, for which the name Sphingomicrobium aestuariivivum sp. nov. is proposed. The type strain is AH-M8T ( = KCTC 42286T = NBRC 110678T).
Phytoactinopolyspora endophytica gen. nov., sp. nov., a halotolerant filamentous actinomycete isolated from the roots of Glycyrrhiza uralensis F.
Authors: Li Li , Ma Jin-Biao , Abdalla Mohamad Osama , Li Shan-Hui , Osman Ghenijan , Li Yan-Qiong , Guo Jian-Wei , Hozzein Wael N. , Li Wen-Jun
Published: May 2015

A novel endophytic actinomycete, designated strain EGI 60009T, was isolated from the roots ofGlycyrrhiza uralensisF. collected from Xinjiang Province, north-west China. The isolate was able to grow in the presence of 0–9 % (w/v) NaCl. Strain EGI 60009Thad particular morphological properties: the substrate mycelia fragmented into rod-like elements and aerial mycelia differentiated into short spore chains.ll-2, 6-Diaminopimelic acid was the cell-wall diamino acid and rhamnose, galactose and glucose were the cell-wall sugars. MK-9(H4) was the predominant menaquinone. The major fatty acids of strain EGI 60009Twere iso-C15 : 0, anteiso-C15 : 0, anteiso-C17 : 0, iso-C17 : 0, iso-C17 : 1and I/anteiso-C17 : 0B. Mycolic acids were absent. The DNA G+C content of strain EGI 60009Twas 70.4 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain EGI 60009Tbelongs to the familyJiangellaceaeand formed a distinct clade in the phylogenetic tree. 16S rRNA gene sequence similarities between strain EGI 60009Tand other members of the generaJiangellaandHaloactinopolysporawere 96.1–96.4 and 95.7–96.0 %, respectively. Based on these results and supported by morphological, physiological and chemotaxonomic data and numerous phenotypic differences, a novel species of a new genus,Phytoactinopolyspora endophyticagen. nov., sp. nov., is proposed. The type strain ofPhytoactinopolyspora endophyticais EGI 60009T( = KCTC 29657T = CPCC204078T).
Whole genome analysis of an extended pedigree with Prader–Willi Syndrome, hereditary hemochromatosis, and dysautonomia-like symptoms
Authors: Fang Han , Wu Yiyang , Yoon Margaret , Jiménez-Barrón Laura T. , O’Rawe Jason A. , Highnam Gareth , Mittelman David , Lyon Gholson J.
Published: May 2015

This report includes the discovery and analysis of a pedigree with Prader–Willi Syndrome (PWS), hereditary hemochromatosis (HH), and dysautonomia-like symptoms. Nine members of the family participated in whole genome sequencing (WGS), which enabled a wide scope of variant calling from single-nucleotide polymorphisms to copy number variations. First, a 5.5 Mbde novodeletion is identified in the chromosome region 15q11.2 to 15q13.1 in the boy with PWS. Second, a female invididual with HH is homozygous for the p.C282Y variant inHFE, a mutation known to be associated with HH. Her brother is homozygous for the same variant, although he has yet to be clinically diagnosed with HH. Third, none of the people with dysautonomia-like symptoms carry any reported or novel rare variants inIKBKAPthat are implicated in familial dysautonomia (FD - HSAN III). Although two people with dysautonomia-like symptoms carry two heterozygous variants inNTRK1, a gene that has been shown to contribute to HSAN IV (congenital insensitivity to pain with anhidrosis, a disease that closely resembles FD), this variant is not present in the third proband. Fourth, WGS revealed pharmacogenetic variants influencing the metabolism of warfarin and simvastatin, which are being routinely prescribed to the proband. Finally, reports of the phenotypes were standardized with the Human Phenotype Ontology annotation, which may facilitate the search for other families with similar phenotypes. Due to the extreme heterogeneity and insufficient knowledge of human diseases, it is of crucial importance that both phenotypic data and genomic data are standardized and shared.
Genome Wide Variant Analysis of Simplex Autism Families with an Integrative Clinical-Bioinformatics Pipeline
Authors: Jiménez-Barrón Laura T. , O’Rawe Jason A. , Wu Yiyang , Yoon Margaret , Fang Han , Iossifov Ivan , Lyon Gholson J.
Published: May 2015

Autism spectrum disorders (ASD) are a group of developmental disabilities that affect social interaction, communication and are characterized by repetitive behaviors. There is now a large body of evidence that suggests a complex role of genetics in ASD, in which many different loci are involved. Although many current population scale genomic studies have been demonstrably fruitful, these studies generally focus on analyzing a limited part of the genome or use a limited set of bioinformatics tools. These limitations preclude the analysis of genome-wide perturbations that may contribute to the development and severity of ASD-related phenotypes. To overcome these limitations, we have developed and utilized an integrative clinical and bioinformatics pipeline for generating a more complete and reliable set of genomic variants for downstream analyses. Our study focuses on the analysis of three simplex autism families consisting of one affected child, unaffected parents, and one unaffected sibling. All members were clinically evaluated and widely phenotyped. Genotyping arrays and whole genome sequencing were performed on each member, and the resulting sequencing data were analyzed using a variety of available bioinformatics tools. We searched for rare variants of putative functional impact that were found to be segregating according to de-novo, autosomal recessive, x-linked, mitochondrial and compound heterozygote transmission models. The resulting candidate variants included three small heterozygous CNVs, a rare heterozygousde novononsense mutation inMYBBP1Alocated within exon 1, and a novelde novomissense variant inLAMB3. Our work demonstrates how more comprehensive analyses that include rich clinical data and whole genome sequencing data can generate reliable results for use in downstream investigations. We are moving to implement our framework for the analysis and study of larger cohorts of families, where statistical rigor can accompany genetic findings.
Bayesian Nonparametric Inference of Population Size Changes from Sequential Genealogies
Authors: Palacios Julia A. , Wakeley John , Ramachandran Sohini
Published: May 2015

Sophisticated inferential tools coupled with the coalescent model have recently emerged for estimating past population sizes from genomic data. Accurate methods are available for data from a single locus or from independent loci. Recent methods that model recombination require small sample sizes, make constraining assumptions about population size changes, and do not report measures of uncertainty for estimates. Here, we develop a Gaussian process-based Bayesian nonparametric method coupled with a sequentially Markov coalescent model which allows accurate inference of population sizes over time from a set of genealogies. In contrast to current methods, our approach considers a broad class of recombination events, including those that do not change local genealogies. We show that our method outperforms recent likelihood-based methods that rely on discretization of the parameter space. We illustrate the application of our method to multiple demographic histories, including population bottlenecks and exponential growth. In simulation, our Bayesian approach produces point estimates four times more accurate than maximum likelihood estimation (based on the sum of absolute differences between the truth and the estimated values). Further, our method’s credible intervals for population size as a function of time cover 90 percent of true values across multiple demographic scenarios, enabling formal hypothesis testing about population size differences over time. Using genealogies estimated withARGweaver, we apply our method to European and Yoruban samples from the 1000 Genomes Project and confirm key known aspects of population size history over the past 150,000 years.
Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells
Authors: Ju Young Seok , Tubio Jose M.C. , Mifsud William , Fu Beiyuan , Davies Helen R. , Ramakrishna Manasa , Li Yilong , Yates Lucy , Gundem Gunes , Tarpey Patrick S. , Behjati Sam , Papaemmanuil Elli , Martin Sancha , Fullam Anthony , Gerstung Moritz ,   ICGC Prostate Cancer Working Group,   ICGC Bone Cancer Working Group,   ICGC Breast Cancer Working Group, Nangalia Jyoti , Green Anthony R. , Caldas Carlos , Borg Åke , Tutt Andrew , Lee Ming Ta Michael , van't Veer Laura J. , Tan Benita K.T. , Aparicio Samuel , Span Paul N. , Martens John W.M. , Knappskog Stian , Vincent-Salomon Anne , Børresen-Dale Anne-Lise , Eyfjörd Jórunn Erla , Myklebost Ola , Flanagan Adrienne M. , Foster Christopher , Neal David E. , Cooper Colin , Eeles Rosalind , Bova G. Steven , Lakhani Sunil R. , Desmedt Christine , Thomas Gilles , Richardson Andrea L. , Purdie Colin A. , Thompson Alastair M. , McDermott Ultan , Yang Fengtang , Nik-Zainal Serena , Campbell Peter J. , Stratton Michael R.
Published: May 2015

Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm, and the mitochondrial double membrane. Despite these physical barriers, we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements, and the features of the fusion fragments indicate that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells.
Down-Regulating the Expression of 53 Soybean Transcription Factor Genes Uncovers a Role for SPEECHLESS in Initiating Stomatal Cell Lineages during Embryo Development
Authors: Danzer John , Mellott Eric , Bui Anhthu Q. , Le Brandon H. , Martin Patrick , Hashimoto Meryl , Perez-Lesher Jeanett , Chen Min , Pelletier Julie M. , Somers David A. , Goldberg Robert B. , Harada John J.
Published: May 2015

We used an RNA interference screen to assay the function of 53 transcription factor messenger RNAs (mRNAs) that accumulate specifically within soybean (Glycine max) seed regions, subregions, and tissues during development. We show that basic helix-loop-helix (bHLH) transcription factor genes represented by Glyma04g41710 and its paralogs are required for the formation of stoma in leaves and stomatal precursor complexes in mature embryo cotyledons. Phylogenetic analysis indicates that these bHLH transcription factor genes are orthologous to Arabidopsis (Arabidopsis thaliana) SPEECHLESS (SPCH) that initiate asymmetric cell divisions in the leaf protoderm layer and establish stomatal cell lineages. Soybean SPCH (GmSPCH) mRNAs accumulate primarily in embryo, seedling, and leaf epidermal layers. Expression of Glyma04g41710 under the control of the SPCH promoter rescues the Arabidopsis spch mutant, indicating that Glyma04g41710 is a functional ortholog of SPCH. Developing soybean embryos do not form mature stoma, and stomatal differentiation is arrested at the guard mother cell stage. We analyzed the accumulation of GmSPCH mRNAs during soybean seed development and mRNAs orthologous to MUTE, FAMA, and INDUCER OF C-REPEAT/DEHYDRATION RESPONSIVE ELEMENT-BINDING FACTOR EXPRESSION1/SCREAM2 that are required for stoma formation in Arabidopsis. The mRNA accumulation patterns provide a potential explanation for guard mother cell dormancy in soybean embryos. Our results suggest that variation in the timing of bHLH transcription factor gene expression can explain the diversity of stomatal forms observed during plant development.
Inference of the Arabidopsis Lateral Root Gene Regulatory Network Suggests a Bifurcation Mechanism That Defines Primordia Flanking and Central Zones
Authors: Lavenus Julien , Goh Tatsuaki , Guyomarc’h Soazig , Hill Kristine , Lucas Mikael , Voß Ute , Kenobi Kim , Wilson Michael H. , Farcot Etienne , Hagen Gretchen , Guilfoyle Thomas J. , Fukaki Hidehiro , Laplaze Laurent , Bennett Malcolm J.
Published: May 2015

A large number of genes involved in lateral root (LR) organogenesis have been identified over the last decade using forward and reverse genetic approaches in Arabidopsis thaliana. Nevertheless, how these genes interact to form a LR regulatory network largely remains to be elucidated. In this study, we developed a time-delay correlation algorithm (TDCor) to infer the gene regulatory network (GRN) controlling LR primordium initiation and patterning in Arabidopsis from a time-series transcriptomic data set. The predicted network topology links the very early-activated genes involved in LR initiation to later expressed cell identity markers through a multistep genetic cascade exhibiting both positive and negative feedback loops. The predictions were tested for the key transcriptional regulator AUXIN RESPONSE FACTOR7 node, and over 70% of its targets were validated experimentally. Intriguingly, the predicted GRN revealed a mutual inhibition between the ARF7 and ARF5 modules that would control an early bifurcation between two cell fates. Analyses of the expression pattern of ARF7 and ARF5 targets suggest that this patterning mechanism controls flanking and central zone specification in Arabidopsis LR primordia.
HEMERA Couples the Proteolysis and Transcriptional Activity of PHYTOCHROME INTERACTING FACTORs in Arabidopsis Photomorphogenesis
Authors: Qiu Yongjian , Li Meina , Pasoreck Elise K. , Long Lingyun , Shi Yiting , Galvão Rafaelo M. , Chou Conrad L. , Wang He , Sun Amanda Y. , Zhang Yiyin C. , Jiang Anna , Chen Meng
Published: May 2015

Phytochromes (phys) are red and far-red photoreceptors that control plant development and growth by promoting the proteolysis of a family of antagonistically acting basic helix-loop-helix transcription factors, the PHYTOCHROME-INTERACTING FACTORs (PIFs). We have previously shown that the degradation of PIF1 and PIF3 requires HEMERA (HMR). However, the biochemical function of HMR and the mechanism by which it mediates PIF degradation remain unclear. Here, we provide genetic evidence that HMR acts upstream of PIFs in regulating hypocotyl growth. Surprisingly, genome-wide analysis of HMR- and PIF-dependent genes reveals that HMR is also required for the transactivation of a subset of PIF direct-target genes. We show that HMR interacts with all PIFs. The HMR-PIF interaction is mediated mainly by HMR's N-terminal half and PIFs’ conserved active-phytochrome B binding motif. In addition, HMR possesses an acidic nine-amino-acid transcriptional activation domain (9aaTAD) and a loss-of-function mutation in this 9aaTAD impairs the expression of PIF target genes and the destruction of PIF1 and PIF3. Together, these in vivo results support a regulatory mechanism for PIFs in which HMR is a transcriptional coactivator binding directly to PIFs and the 9aaTAD of HMR couples the degradation of PIF1 and PIF3 with the transactivation of PIF target genes.
The structure of the first stable monosubstituted sulfur diimide
Authors: Jones Ray
Published: May 2015

The title compound, 4-(4-methylphenyl)-1,3-diaza-2,4-dithiabuta-1,2-diene, C7H8N2S2, was the first example of a stable monosubstituted sulfur diimide to be documented [Jones (1988). PhD thesis, Imperial College, University of London, England]. Although a partial description of this structure was published previously, the full details are presented here. This allows a detailed comparison against the only other example of this system published to date, highlighting differences in bonding, conformation and packing.
The exopolyhedral ligand orientation (ELO) in 3-(nitrato-κO)-3,3-bis(triphenylphosphane-κP)-3-rhoda-1,2-dicarba-closo-dodecaborane(11) dichloromethane 2.2-solvate
Authors: Rosair Georgina M. , Scott Greig , Welch Alan J.
Published: May 2015

In the title compound, [Rh(C2H11B9)(NO3)(C18H15P)2]·2.2CH2Cl2, studied as a 2.2-solvate of what was assumed to be dichloromethane, the nitrate ligand liesciswith respect to both cage C atoms. Accordingly, the compound displays a pronounced preferred exopolyhedral ligand orientation (ELO) which is traced to both the greatertransinfluence of the cage B over the cage C atoms and the greatertransinfluence of the triphenylphosphane ligands over the nitrate ligand. The overall molecular architecture therefore agrees with that of a number of similar 3-L-3,3-L′2-3,1,2-closo-MC2B9H11species in the literature.
Crystal structures of five (2-chloroquinolin-3-yl)methyl ethers: supramolecular assembly in one and two dimensions mediated by hydrogen bonding and π–π stacking
Authors: Sowmya Haliwana B. V. , Suresha Kumara Tholappanavara H. , Gopalpur Nagendrappa , Jasinski Jerry P. , Millikan Sean P. , Yathirajan Hemmige S. , Glidewell Christopher
Published: May 2015

In the molecules of the title compounds, methyl 5-bromo-2-[(2-chloroquinolin-3-yl)methoxy]benzoate, C18H13BrClNO3, (I), methyl 5-bromo-2-[(2-chloro-6-methylquinolin-3-yl)methoxy]benzoate, C19H15BrClNO3, (II), methyl 2-[(2-chloro-6-methylquinolin-3-yl)methoxy]benzoate, C19H16ClNO3, (III), which crystallizes withZ′ = 4 in space groupP212121, and 2-chloro-3-[(naphthalen-1-yloxy)methyl]quinoline, C20H14ClNO, (IV), the non-H atoms are nearly coplanar, but in {5-[(2-chloroquinolin-3-yl)methoxy]-4-(hydroxymethyl)-6-methylpyridin-3-yl}methanol, C18H17ClN2O3, (V), the planes of the quinoline unit and of the unfused pyridine ring are almost parallel, although not coplanar. The molecules of (I) are linked by two independent π–π stacking interactions to form chains, but there are no hydrogen bonds present in the structure. In (II), the molecules are weakly linked into chains by a single type of π–π stacking interaction. In (III), three of the four independent molecules are linked by π–π stacking interactions but the other molecule does not participate in such interactions. Weak C—H...O hydrogen bonds link the molecules into three types of chains, two of which contain just one type of independent molecule while the third type of chain contains two types of molecule. The molecules of (IV) are linked into chains by a C—H...π(arene) hydrogen bond, but π–π stacking interactions are absent. In (V), there is an intramolecular O—H...O hydrogen bond, and molecules are linked into sheets by a combination of O—H...N hydrogen bonds and π–π stacking interactions.
Crystal structure of 4-[(5-methylisoxazol-3-yl)aminosulfonyl]anilinium 3,5-dinitrosalicylate
Authors: Malathy Sevaiyan , Nirmalram Jeyaraman Selvaraj , Muthiah Packianathan Thomas
Published: May 2015

The title molecular salt, C10H12N3O3S+·C7H3N2O7−, protonation occurs at the amino N atom attached to the benzene ring of sulfamethoxazole. In the anion, there is an intramolecular O—H...O hydrogen bond and the cation is linked to the anion by an N—H...O hydrogen bond. In the extended structure, the cations and anions are linkedviaN—H...O, N—H...N and C—H...O hydrogen bonds, forming a three-dimensional framework.
Redetermined crystal structure of β-DL-methionine at 320 K
Authors: Görbitz Carl Henrik , Paulsen Jan Christian , Borgersen Jon
Published: May 2015

The structure of β-DL-methionine, C5H11NO2S, in the space groupC2/c, is here confirmed to be fully ordered all the way up to the phase transition at approximately 326 K, where displacive sliding of molecular bilayers gives the disorderedP21/cα form [data at 340 K; Görbitz (2014).Acta Cryst.E70, 341–343]. The geometry of hydrogen bonds in LD–LD hydrogen-bonding patterns [Görbitzet al.(2009).Acta Cryst.B65, 393–400] at the hydrophilic core of each molecular bilayer are virtually unperturbed by the phase shift, but the C—C—S—C torsion angle of the side chain changes fromtransat 320 K togauche+ for the major conformation at 340 K.
Crystal structure of 3-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydrocyclopenta[b]indole-2-carboxylic acid
Authors: Fernandes Daniara , Simoni Deborah de Alencar , Rodrigues Manoel T. , Santos Marilia S. , Coelho Fernando
Published: May 2015

In the title compound, C21H21NO5, obtained from a Morita–Baylis–Hillman adduct, the hydrogenated five-membered ring adopts a shallow envelope conformation, with the C atom bearing the carboxylic acid substituent deviating by 0.237 (1) Å from the mean plane of the other four atoms (r.m.s. deviation = 0.007 Å). The dihedral angle between the fused ring system (all atoms; r.m.s. deviation = 0.057 Å) and the pendant trimethoxy benzene ring is 66.65 (3)°. The C atoms of themeta-methoxy groups lie close to the plane of the benzene ring [deviations = 0.052 (1) and −0.083 (1) Å], whereas the C atom of thepara-methoxy group is significantly displaced [deviation = −1.289 (1) Å]. In the crystal, carboxylic acid inversion dimers generateR22(8) loops. The dimers are connected by N—H...O hydrogen bonds, forming [011] chains. A C—H...O interaction is also observed.
Crystal structure oftert-butyldiphenylphosphine oxide
Authors: Agbeworvi George , Assefa Zerihun , Sykora Richard E. , Taylor Jared D.
Published: May 2015

In the structure of the title triorganophosphine oxide, C16H19OP, the P—O bond is 1.490 (1) Å. The P atom has a distorted tetrahedral geometry. The O atom interacts with both phenyl groups of a neighboring molecule [C...O = 2.930 (3) and 2.928 (4) Å]. The C—O interaction directs an extended supramolecular arrangement along thea-axis.
Economic welfare as ethical concept and economic policy
Authors: Merrill David
Published: May 2015

Purpose

– Paper argues that the proper approach to the topic of economic welfare should include an appreciation that markets are not characterized by an endogenous tendency towards equilibrium. The economists, Schumpeter, Keynes and Minsky are right in this regard as opposed to Adam Smith and contemporary economic orthodoxy. However, today’s liberal political theories largely assumes the tendency towards equilibrium and so are inadequate to deal with economic issues such as economic welfare which arise in conditions of non-equilibrium. The purpose of this paper is to propose Winfield’s reconstruction of Hegel’s social philosophy as more fitted to deal with market realities.

Design/methodology/approach

– Paper starts with a debate within economics and uses it as a basis to evaluate different schools of normative philosophy. Paper concludes by showing how the preferred philosophy is capable to rule between different economic policies responding to economic disequilibrium.

Findings

– Hegelian philosophy has capacity to adjudicate between economic policies to resolve market failure that contemporary liberal theory lacks.

Practical implications

– Paper provides the ethical justification for economic policies that have heretofore only been recommend by economists.

Originality/value

– Paper points to the largely overlooked fact that most contemporary political theory assumes market equilibrium. Paper argues that Hegelian philosophy provides the ethical justification for certain post-Keynesian economic policies, a position no one else is making.