bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coping with complexity: Developmental systems and multilevel analyses in developmental psychopathology
Authors: Marshall Peter J. 
Published: December 2013

AbstractDevelopmental psychopathology is not characterized by adherence to one specific theory but instead serves as an organizational framework in which research is driven by a number of key assumptions. In the developmental psychopathology approach, two primary assumptions emphasize the importance of systems thinking and the utility of multilevel analyses. As will be illustrated here, these emphases are inextricably linked: a systems approach necessitates a multilevel approach, such that a level of organization must bring coherence to a level of mechanisms. Given this assumption, coming to an integrative understanding of the relation between levels is of central importance. One broad framework for this endeavor is relational developmental systems, which has been proposed by certain theorists as a new paradigm for developmental science. The implications of embracing this framework include the potential to connect developmental psychopathology with other approaches that emphasize systems thinking and that take an integrative perspective on the problem of levels of analysis.
On expletive subject pronoun drop in Colloquial French
Authors: ZIMMERMANN MICHAEL , KAISER GEORG A. 
Published: December 2013

ABSTRACTThis paper sets out to contribute to the debate on the morpho-syntactic status of phonologically weak or clitic subject pronouns in Colloquial French by discussing finite impersonal constructions in which the expletive subject pronoun is non-expressed. The paper provides arguments against an approach in terms of inflectional affixes, showing that the non-expression of this pronoun is in fact syntactically restricted. On the basis of the further finding that the non-expression of the expletive represents the continuation of a grammatical trait of older stages of the language in which the non-expression of subject pronouns was generally possible, a tentative proposal is put forward which crucially draws on information structure.
Anomalous left coronary artery from the right coronary cusp with gene positive apical hypertrophic cardiomyopathy: a case report and literature review
Authors: Georgekutty Justin , Cross Russell R. , Rosenthal Joanna B. , Heath Deneen M. , Sinha Pranava , John Anitha S. 
Published: December 2013

AbstractIn the United States, hypertrophic cardiomyopathy and coronary artery anomalies account for the leading two causes of sudden death in athletes. We present a case of a patient with an anomalous origin of the left main from the right coronary sinus with associated gene-confirmed hypertrophic cardiomyopathy. The patient underwent surgical repair with unroofing of the intramural portion of the left main coronary artery with a good result. We also review the reported cases in the medical literature describing this uncommon association between anomalous coronary artery origin and hypertrophic cardiomyopathy.
Pre-erythrocytic antibody profiles induced by controlled human malaria infections in healthy volunteers under chloroquine prophylaxis
Authors: Felgner Philip L. , Roestenberg Meta , Liang Li , Hung Christopher , Jain Aarti , Pablo Jozelyn , Nakajima-Sasaki Rie , Molina Douglas , Teelen Karina , Hermsen Cornelus C. , Sauerwein Robert 
Published: December 2013

AbstractComplete sterile protection to Plasmodium falciparum (Pf) infection mediated by pre-erythrocytic immunity can be experimentally induced under chloroquine prophylaxis, through immunization with sporozoites from infected mosquitoes' bites (CPS protocol). To characterize the profile of CPS induced antibody (Ab) responses, we developed a proteome microarray containing 809 Pf antigens showing a distinct Ab profile with recognition of antigens expressed in pre-erythrocytic life-cycle stages. In contrast, plasma from naturally exposed semi-immune individuals from Kenya was skewed toward antibody reactivity against asexual blood stage antigens. CPS-immunized and semi-immune individuals generated antibodies against 192 and 202 Pf antigens, respectively, but only 60 antigens overlapped between the two groups. Although the number of reactive antigens varied between the CPS-immunized individuals, all volunteers reacted strongly against the pre-erythrocytic antigens circumsporozoite protein (CSP) and liver stage antigen 1 (LSA1). Well classified merozoite and erythrocytic antigens were strongly reactive in semi-immune individuals but lacking in the CPS immunized group. These data show that the antibody profile of CPS-immunized and semi-immune groups have quite distinct profiles reflecting their protective immunity; antibodies from CPS immunized individuals react strongly against pre-erythrocytic while semi-immune individuals mainly react against erythrocytic antigens.
A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia
Authors: Bentsen H , Osnes K , Refsum H , Solberg D K , Bøhmer T 
Published: December 2013

AbstractMembrane lipid metabolism and redox regulation may be disturbed in schizophrenia. We examined the clinical effect of adding an omega-3 fatty acid and/or vitamins E+C to antipsychotics. It was hypothesized that lower baseline levels of polyunsaturated fatty acids (PUFAs) would predict more benefit from the add-on treatment. The trial had a multicenter, randomized, double-blind, placebo-controlled 2 × 2 factorial design. Patients aged 18–39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway. They received active or placebo ethyl-eicosapentaenoate (EPA) 2 g day−1 and active or placebo vitamin E 364 mg day−1+vitamin C 1000 mg day−1 (vitamins) for 16 weeks. The main outcome measures were Positive and Negative Syndrome Scale (PANSS) total and subscales scores, analyzed by linear mixed models. Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. Given separately, EPA and vitamins increased drop-out rates, whereas when combined they did not differ from placebo. In low PUFA patients, EPA alone impaired the course of total PANSS (Cohen’s d=0.29; P=0.03) and psychotic symptoms (d=0.40; P=0.003), especially persecutory delusions (d=0.48; P=0.0004). Vitamins alone impaired the course of psychotic symptoms (d= 0.37; P=0.005), especially persecutory delusions (d=0.47; P=0.0005). Adding vitamins to EPA neutralized the detrimental effect on psychosis (interaction d=0.31; P=0.02). In high PUFA patients, there were no significant effects of trial drugs on PANSS scales. In conclusion, given separately during an acute episode, EPA and vitamins E+C induce psychotic symptoms in patients with low levels of PUFA. Combined, these agents seem safe.
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

SignificanceTrophy 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.
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

SignificanceSeveral 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.
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

Abstract
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

Abstract
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

AbstractPerturbations 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

Abstract
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.