bluuebunny/crossref_metadata_2025_split huggingface dataset:
Follow-up of congenital heart disease patients with subclinical hypothyroidism
Authors: Martínez-Quintana Efrén , Rodríguez-González Fayna 
Published: September 2014

AbstractIntroduction: Subclinical hypothyroidism or mild thyroid failure is a common problem in patients without known thyroid disease. Methods: Demographic and analytical data were collected in 309, of which 181 were male and 128 were female, congenital heart disease (CHD) patients. CHD patients with thyroid-stimulating hormone above 5.5 mIU/L were also followed up from an analytical point of view to determine changes in serum glucose, cholesterol, N-terminal pro b-type natriuretic peptide, and C-reactive protein concentrations. Results: Of the CHD patients, 35 (11.3%) showed thyroid-stimulating hormone concentration above 5.5 mIU/L. Of them, 27 were followed up during 2.4±1.2 years – 10 were under thyroid hormone replacement treatment, and 17 were not. Of the 27 patients (25.9%), 7 with subclinical hypothyroidism had positive anti-thyroid peroxidase, and 3 of them (42.8%) with positive anti-thyroid peroxidase had Down syndrome. Down syndrome and hypoxaemic CHD patients showed higher thyroid-stimulating hormone concentrations than the rest of the congenital patients (p<0.001). No significant differences were observed in serum thyroxine, creatinine, uric acid, lipids, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations before and after the follow-up in those CHD patients with thyroid-stimulating hormone above 5.5 mIU/L whether or not they received levothyroxine therapy. Conclusions: CHD patients with subclinical hypothyroidism showed no significant changes in serum thyroxine, cholesterol, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations whether or not they were treated with thyroid hormone replacement therapy.
Are APOE ɛ genotype and TOMM40 poly-T repeat length associations with cognitive ageing mediated by brain white matter tract integrity?
Authors: Lyall D M , Harris S E , Bastin M E , Muñoz Maniega S , Murray C , Lutz M W , Saunders A M , Roses A D , Valdés Hernández M del C , Royle N A , Starr J M , Porteous D J , Wardlaw J M , Deary I J 
Published: September 2014

AbstractGenetic polymorphisms in the APOE ɛ and TOMM40 ‘523’ poly-T repeat gene loci have been associated with significantly increased risk of Alzheimer’s disease. This study investigated the independent effects of these polymorphisms on human cognitive ageing, and the extent to which nominally significant associations with cognitive ageing were mediated by previously reported genetic associations with brain white matter tract integrity in this sample. Most participants in the Lothian Birth Cohort 1936 completed a reasoning-type intelligence test at age 11 years, and detailed cognitive/physical assessments and structural diffusion tensor brain magnetic resonance imaging at a mean age of 72.70 years (s.d.=0.74). Participants were genotyped for APOE ɛ2/ɛ3/ɛ4 status and TOMM40 523 poly-T repeat length. Data were available from 758–814 subjects for cognitive analysis, and 522–543 for mediation analysis with brain imaging data. APOE genotype was significantly associated with performance on several different tests of cognitive ability, including general factors of intelligence, information processing speed and memory (raw P-values all<0.05), independently of childhood IQ and vascular disease history. Formal tests of mediation showed that several significant APOE-cognitive ageing associations—particularly those related to tests of information processing speed—were partially mediated by white matter tract integrity. TOMM40 523 genotype was not associated with cognitive ageing. A range of brain phenotypes are likely to form the anatomical basis for significant associations between APOE genotype and cognitive ageing, including white matter tract microstructural integrity.
Atmospheric controls on northeast Pacific temperature variability and change, 1900–2012
Authors: Johnstone James A. , Mantua Nathan J. 
Published: September 2014

Significance
Northeast Pacific coastal warming since 1900 is often ascribed to anthropogenic greenhouse forcing, whereas multidecadal temperature changes are widely interpreted in the framework of the Pacific Decadal Oscillation (PDO), which responds to regional atmospheric dynamics. This study uses several independent data sources to demonstrate that century-long warming around the northeast Pacific margins, like multidecadal variability, can be primarily attributed to changes in atmospheric circulation. It presents a significant reinterpretation of the region’s recent climate change origins, showing that atmospheric conditions have changed substantially over the last century, that these changes are not likely related to historical anthropogenic and natural radiative forcing, and that dynamical mechanisms of interannual and multidecadal temperature variability can also apply to observed century-long trends.
Toward a theory of resilience for international development applications
Authors: Barrett Christopher B. , Constas Mark A. 
Published: September 2014

Significance
This paper lays the theoretical groundwork necessary to inform more precise use of the term “resilience,” to articulate better theories of change, and to promote more focused measures of resilience for international development applications. Our work complements a flurry of recent notes, white papers, and policy briefs on resilience, all offering measurement tools, policy and programming prescriptions, etc., but conspicuously without any explicit theory of resilience as might be applied to the lives of the poor.
Human preferences for sexually dimorphic faces may be evolutionarily novel
Authors: Scott Isabel M. , Clark Andrew P. , Josephson Steven C. , Boyette Adam H. , Cuthill Innes C. , Fried Ruby L. , Gibson Mhairi A. , Hewlett Barry S. , Jamieson Mark , Jankowiak William , Honey P. Lynne , Huang Zejun , Liebert Melissa A. , Purzycki Benjamin G. , Shaver John H. , Snodgrass J. Josh , Sosis Richard , Sugiyama Lawrence S. , Swami Viren , Yu Douglas W. , Zhao Yangke , Penton-Voak Ian S. 
Published: September 2014

Significance
It is a popular assumption that certain perceptions—for example, that highly feminine women are attractive, or that masculine men are aggressive—reflect evolutionary processes operating within ancestral human populations. However, observations of these perceptions have mostly come from modern, urban populations. This study presents data on cross-cultural perceptions of facial masculinity and femininity. In contrast to expectations, we find that in less developed environments, typical “Western” perceptions are attenuated or even reversed, suggesting that Western perceptions may be relatively novel. We speculate that novel environments, which expose individuals to large numbers of unfamiliar faces, may provide novel opportunities—and motives—to discern subtle relationships between facial appearance and other traits.
Alternating antibiotic treatments constrain evolutionary paths to multidrug resistance
Authors: Kim Seungsoo , Lieberman Tami D. , Kishony Roy 
Published: September 2014

Significance
Antibiotic resistance is a growing threat, but the pace of drug discovery remains slow. Combination therapy can inhibit the emergence of de novo resistance but is often too toxic for long-term use. Alternating treatments, in which drugs are used sequentially with periodic switching, have been proposed as a substitute, but it remains uncertain when and how they slow the evolution of resistance. Using experimental evolution and whole-genome sequencing, we find that alternating drugs slows the rate of increase in resistance compared with single-drug treatments, by constraining resistance mutations with trade-offs in resistance to a second drug. Thus, drug combinations can exploit these trade-offs to slow the evolution of resistance, even when the drugs are not used simultaneously.
Antifreeze protein-induced superheating of ice inside Antarctic notothenioid fishes inhibits melting during summer warming
Authors: Cziko Paul A. , DeVries Arthur L. , Evans Clive W. , Cheng Chi-Hing Christina 
Published: September 2014

SignificanceAntarctic notothenioid fishes are protected from freezing by antifreeze proteins (AFPs) that bind to invading ice crystals and inhibit their growth. Paradoxically, accumulation of AFP-stabilized ice could be lethal. Whether and how fishes eliminate internal ice is unknown; one hypothesis is that it melts during summer warming episodes. However, prior in vitro evidence indicates that AFPs also inhibit melting. Our study establishes that pronounced melting inhibition occurs in vivo (i.e., superheated ice occurs inside notothenioid fishes). Our long-term temperature record of a high-latitude Antarctic fish habitat indicates that summer warming does not overcome AFP-induced superheating to reliably rid fishes of ice. Evolution of the life-saving AFPs exacts a cost: the risk of lifelong accumulation of damaging internal ice crystals.
Deleting titin’s I-band/A-band junction reveals critical roles for titin in biomechanical sensing and cardiac function
Authors: Granzier Henk L. , Hutchinson Kirk R. , Tonino Paola , Methawasin Mei , Li Frank W. , Slater Rebecca E. , Bull Mathew M. , Saripalli Chandra , Pappas Christopher T. , Gregorio Carol C. , Smith John E. 
Published: September 2014

Significance
Mutations in titin are a major cause of heart failure, yet the functions of large parts of titin are not understood. Here we studied titin’s I-band/A-band junction that has been proposed to be crucial for thick filament length control. We made a mouse in which titin’s IA junction was deleted. Super-resolution microscopy (structured illumination microscopy) revealed that deleting the IA junction increases the strain on titin’s molecular spring elements without altering thick filament length. Single cell biomechanical measurements showed that this increases passive stiffness while functional studies at the whole animal level revealed diastolic dysfunction, exercise intolerance, and modest concentric cardiac hypertrophy—signature features of heart failure with preserved ejection fraction. Our studies support that titin is a promising therapeutic target for treating heart failure.
Iron oxides stimulate sulfate-driven anaerobic methane oxidation in seeps
Authors: Sivan Orit , Antler Gilad , Turchyn Alexandra V. , Marlow Jeffrey J. , Orphan Victoria J. 
Published: September 2014

Significance
Anaerobic oxidation of methane (AOM) coupled to sulfate reduction has been shown to consume up to 90% of the greenhouse gas methane produced within the subseafloor environment; however, the mechanism of this process has remained enigmatic. Here, we provide geochemical evidence based on sulfur, oxygen, and carbon isotopes for the involvement of iron oxides in sulfate-driven AOM in methane seeps. Our results suggest that, beyond the function of iron as nutrient, the presence of iron oxides stimulates sulfate-driven AOM to a greater extent than in sediments with low concentrations of iron oxides. The isotope analyses further indicate that sulfate reduction in methane seep habitats differs than sulfate reduction in diffusive profiles in and above the sulfate–methane transition zone.
Multistep hierarchical self-assembly of chiral nanopore arrays
Authors: Kim Hanim , Lee Sunhee , Shin Tae Joo , Korblova Eva , Walba David M. , Clark Noel A. , Lee Sang Bok , Yoon Dong Ki 
Published: September 2014

SignificanceBent-core mesogenic molecules form smectic liquid crystal phases in which the molecular layers are locally polar and chiral, and have a built-in tendency for saddle splay curvature, a combination that fills bulk neat bent-core smectics with self-assembled helical nanofilament bundles of twisted layers. This observation led us to explore the growth mode of such smectics under conditions of nanoconfinement and the remarkable observation reported here that single nanofilaments readily grow in linear nanoscale pores, generating a new motif of hierarchically self-assembled hybrid organic/inorganic structures for applications in chiral synthesis and separation.
Bimodal activation of BubR1 by Bub3 sustains mitotic checkpoint signaling
Authors: Han Joo Seok , Vitre Benjamin , Fachinetti Daniele , Cleveland Don W. 
Published: September 2014

Significance
The mitotic checkpoint (or the spindle assembly checkpoint) ensures genome integrity by preventing premature chromosome segregation. The pathway is triggered locally by kinetochores, multiprotein complexes assembled onto centromeres. Unattached kinetochores produce Mad2 bound to Cdc20, the mitotic activator of the E3 ubiquitin ligase APC/C. The initial Mad2–Cdc20 complex is then converted into the final mitotic checkpoint inhibitor Bub3–BubR1–Cdc20 that blocks APC/C (anaphase promoting complex or cyclosome)-dependent ubiquitination of cyclin B and securin, thereby stabilizing them and preventing an advance to anaphase. In this study, we identify dual mechanisms by which Bub3 promotes mitotic checkpoint signaling. Bub3 binding to BubR1 promotes two distinct BubR1–Cdc20 interactions, one acting at unattached kinetochores and the other cytoplasmically to facilitate production of the mitotic checkpoint inhibitor.
α-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation
Authors: Burré Jacqueline , Sharma Manu , Südhof Thomas C. 
Published: September 2014

SignificancePhysiologically, α-synuclein promotes soluble NSF attachment protein receptor (SNARE) complex assembly during synaptic exocytosis. Pathologically, however, α-synuclein forms neurotoxic aggregates that promote neurodegeneration and represent hallmarks of Parkinson's disease and other synucleinopathies. α-Synuclein exists in a monomeric unfolded state in solution and in an α-helical folded state upon binding to membranes. Yet the relation between these conformational states and their physiological and pathological roles remain unknown. Here, we demonstrate that α-synuclein multimerizes during membrane binding and that the membrane-bound, multimeric form of α-synuclein mediates SNARE complex assembly in presynaptic terminals. Our data delineate a folding pathway for α-synuclein that ranges from a monomeric unfolded form in cytosol to a physiologically functional multimeric form that is membrane bound and chaperones SNARE complex assembly, and that may protect against neurodegeneration.
NAIL, a software toolset for inferring, analyzing and visualizing regulatory networks
Authors: Hurley Daniel G. , Cursons Joseph , Wang Yi Kan , Budden David M. , Print Cristin G. , Crampin Edmund J. 
Published: September 2014

Abstract
Summary : The wide variety of published approaches for the problem of regulatory network inference makes using multiple inference algorithms complex and time-consuming. Network Analysis and Inference Library (NAIL) is a set of software tools to simplify the range of computational activities involved in regulatory network inference. It uses a modular approach to connect different network inference algorithms to the same visualization and network-based analyses. NAIL is technology-independent and includes an interface layer to allow easy integration of components into other applications.
Availability and implementation : NAIL is implemented in MATLAB, runs on Windows, Linux and OSX, and is available from SourceForge at https://sourceforge.net/projects/nailsystemsbiology/ for all researchers to use.
Contact : daniel.hurley@unimelb.edu.au
Supplementary information : Supplementary data are available at Bioinformatics online.
Reproducibility of telomere length assessment: an international collaborative study
Authors: Martin-Ruiz Carmen M , Baird Duncan , Roger Laureline , Boukamp Petra , Krunic Damir , Cawthon Richard , Dokter Martin M , van der Harst Pim , Bekaert Sofie , de Meyer Tim , Roos Goran , Svenson Ulrika , Codd Veryan , Samani Nilesh J , McGlynn Liane , Shiels Paul G , Pooley Karen A , Dunning Alison M , Cooper Rachel , Wong Andrew , Kingston Andrew , von Zglinicki Thomas 
Published: September 2014

AbstractBackground: Telomere length is a putative biomarker of ageing, morbidity and mortality. Its application is hampered by lack of widely applicable reference ranges and uncertainty regarding the present limits of measurement reproducibility within and between laboratories.Methods: We instigated an international collaborative study of telomere length assessment: 10 different laboratories, employing 3 different techniques [Southern blotting, single telomere length analysis (STELA) and real-time quantitative PCR (qPCR)] performed two rounds of fully blinded measurements on 10 human DNA samples per round to enable unbiased assessment of intra- and inter-batch variation between laboratories and techniques.Results: Absolute results from different laboratories differed widely and could thus not be compared directly, but rankings of relative telomere lengths were highly correlated (correlation coefficients of 0.63–0.99). Intra-technique correlations were similar for Southern blotting and qPCR and were stronger than inter-technique ones. However, inter-laboratory coefficients of variation (CVs) averaged about 10% for Southern blotting and STELA and more than 20% for qPCR. This difference was compensated for by a higher dynamic range for the qPCR method as shown by equal variance after z-scoring. Technical variation per laboratory, measured as median of intra- and inter-batch CVs, ranged from 1.4% to 9.5%, with differences between laboratories only marginally significant ( P  = 0.06). Gel-based and PCR-based techniques were not different in accuracy.Conclusions: Intra- and inter-laboratory technical variation severely limits the usefulness of data pooling and excludes sharing of reference ranges between laboratories. We propose to establish a common set of physical telomere length standards to improve comparability of telomere length estimates between laboratories.
Mucolipin 1 positively regulates TLR7 responses in dendritic cells by facilitating RNA transportation to lysosomes
Authors: Li Xiaobing , Saitoh Shin-ichiroh , Shibata Takuma , Tanimura Natsuko , Fukui Ryutaro , Miyake Kensuke 
Published: September 2014

Abstract
Toll-like receptor 7 (TLR7) and TLR9 sense microbial single-stranded RNA (ssRNA) and ssDNA in endolysosomes. Nucleic acid (NA)-sensing in endolysosomes is thought to be important for avoiding TLR7/9 responses to self-derived NAs. Aberrant self-derived NA transportation to endolysosomes predisposes to autoimmune diseases. To restrict NA-sensing in endolysosomes, TLR7/9 trafficking is tightly controlled by a multiple transmembrane protein Unc93B1. In contrast to TLR7/9 trafficking, little is known about a mechanism underlying NA transportation. We here show that Mucolipin 1 (Mcoln1), a member of the transient receptor potential (TRP) cation channel gene family, has an important role in ssRNA trafficking into lysosomes. Mcoln1−/− dendritic cells (DCs) showed impaired TLR7 responses to ssRNA. A mucolipin agonist specifically enhanced TLR7 responses to ssRNAs. The channel activity of Mcoln1 is activated by a phospholipid phosphatidylinositol (3,5) bisphosphate (PtdIns(3,5)P2), which is generated by a class III lipid kinase PIKfyve. A PIKfyve inhibitor completely inhibited TLR7 responses to ssRNA in DCs. Confocal analyses showed that ssRNA transportation to lysosomes in DCs was impaired by PIKfyve inhibitor as well as by the lack of Mcoln1. Transportation of TLR9 ligands was also impaired by the PIKfyve inhibitor. These results demonstrate that the PtdIns(3,5)P2–Mcoln1 axis has an important role in ssRNA transportation into lysosomes in DCs.
Establishment of a vascular endothelial cell-reactive type II NKT cell clone from a rat model of autoimmune vasculitis
Authors: Iinuma Chihiro , Waki Masashi , Kawakami Ai , Yamaguchi Madoka , Tomaru Utano , Sasaki Naomi , Masuda Sakiko , Matsui Yuki , Iwasaki Sari , Baba Tomohisa , Kasahara Masanori , Yoshiki Takashi , Paletta Daniel , Herrmann Thomas , Ishizu Akihiro 
Published: September 2014

Abstract
We previously generated a rat model that spontaneously developed small vessel vasculitis (SVV). In this study, a T cell clone reactive with rat vascular endothelial cells (REC) was established and named VASC-1. Intravenous injection of VASC-1 induced SVV in normal recipients. VASC-1 was a TCRαβ/CD3-positive CD4/CD8 double-negative T cell clone with expression of NKG2D. The cytokine mRNA profile under unstimulated condition was positive for IL-4 and IFN-γ but negative for IL-2 and IL-10. After interaction with REC, the mRNA expression of IL-2, IL-5 and IL-6 was induced in VASC-1, which was inhibited by blocking of CD1d on the REC surface. Although the protein levels of these cytokines seemed to be lower than the detection limit in the culture medium, IFN-γ was detectable. The production of IFN-γ from the VASC-1 stimulated with LPS-pre-treated REC was inhibited by the CD1d blockade on the REC. These findings indicated VASC-1 as an NKT cell clone. The NKT cell pool includes two major subsets, namely types I and II. Type I NKT cells are characterized by expression of semi-invariant TCRs and the potential to bind to marine sponge-derived α-galactosylceramide (α-GalCer) loaded on CD1d; whereas, type II NKT cells do not manifest these characteristics. VASC-1 exhibited a usage of TCR other than the type I invariant TCR α chain and did not bind to α-GalCer-loaded CD1d; therefore, it was determined as a type II NKT cell clone. The collective evidence suggested that REC-reactive type II NKT cells could be involved in the pathogenesis of SVV in rats.
Unleashing the clinical power of T cells: CD19/CD3 bi-specific T cell engager (BiTE®) antibody construct blinatumomab as a potential therapy
Authors: Zimmerman Zachary , Maniar Tapan , Nagorsen Dirk 
Published: September 2014

Abstract
Multi-agent chemotherapy is the standard treatment for most B cell malignancies. Since chemotherapy can be associated with significant toxicity and since relapses resistant to chemotherapy often develop, new therapies are needed. Blinatumomab (AMG 103 or MT103) is a late-stage candidate in clinical development, which belongs to a novel class of antibody constructs termed bi-specific T cell engager antibodies. This antibody construct has dual specificity for CD19 and CD3 and can re-direct polyclonal cytotoxic T lymphocytes toward the tumor. This review focuses on the pre-clinical and clinical development of blinatumomab as a powerful new tool in the treatment of B cell malignancies.