bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis for the mechanism of ABC transporters
Authors: Beis Konstantinos 
Published: October 2015

The ATP-binding cassette (ABC) transporters are primary transporters that couple the energy stored in adenosine triphosphate (ATP) to the movement of molecules across the membrane. ABC transporters can be divided into exporters and importers; importers mediate the uptake of essential nutrients into cells and are found predominantly in prokaryotes whereas exporters transport molecules out of cells or into organelles and are found in all organisms. ABC exporters have been linked with multi-drug resistance in both bacterial and eukaryotic cells. ABC transporters are powered by the hydrolysis of ATP and transport their substrate via the alternating access mechanism, whereby the protein alternates between a conformation in which the substrate-binding site is accessible from the outside of the membrane, outward-facing and one in which it is inward-facing. In this mini-review, the structures of different ABC transporter types in different conformations are presented within the context of the alternating access mechanism and how they have shaped our current understanding of the mechanism of ABC transporters.
The centriolar protein CPAP G-box: an amyloid fibril in a single domain
Authors: Cutts Erin E. , Inglis Alison , Stansfeld Phillip J. , Vakonakis Ioannis , Hatzopoulos Georgios N. 
Published: October 2015

Centrioles are evolutionarily conserved cylindrical cell organelles with characteristic radial symmetry. Despite their considerable size (400 nm × 200 nm, in humans), genetic studies suggest that relatively few protein components are involved in their assembly. We recently characterized the molecular architecture of the centrosomal P4.1-associated protein (CPAP), which is crucial for controlling the centriolar cylinder length. Here, we review the remarkable architecture of the C-terminal domain of CPAP, termed the G-box, which comprises a single, entirely solvent exposed, antiparallel β-sheet. Molecular dynamics simulations support the stability of the G-box domain even in the face of truncations or amino acid substitutions. The similarity of the G-box domain to amyloids (or amyloid precursors) is strengthened by its oligomeric arrangement to form continuous fibrils. G-box fibrils were observed in crystals as well as in solution and are also supported by simulations. We conclude that the G-box domain may well represent the best analogue currently available for studies of exposed β-sheets, unencumbered by additional structural elements or severe aggregations problems.
Tribbles breaking bad: TRIB2 suppresses FOXO and acts as an oncogenic protein in melanoma
Authors: Link Wolfgang 
Published: October 2015

TRIB2 (tribbles homolog 2) encodes one of three members of the tribbles family in mammals. These members share a Trb (tribbles) domain, which is homologous to protein serine-threonine kinases, but lack the active site lysine. The tribbles proteins interact and modulate the activity of signal transduction pathways in a number of physiological and pathological processes. TRIB2 has been identified as an oncogene that inactivates the transcription factor CCAAT/enhancer-binding protein α (C/EBPα) and causes acute myelogenous leukaemia (AML). Recent research provided compelling evidence that TRIB2 can also act as oncogenic driver in solid tumours, such as lung and liver cancer. In particular, our recent work demonstrated that TRIB2 is dramatically overexpressed in malignant melanomas compared with normal skin and promotes the malignant phenotype of melanoma cells via the down-regulation of FOXO (forkhead box protein O) tumour suppressor activity in vitro and in vivo. TRIB2 was found to be expressed in normal skin, but its expression consistently increased in benign nevi, melanoma and was highest in samples from patients with malignant melanoma. The observation that TRIB2 strongly correlates with the progression of melanocyte-derived malignancies suggests TRIB2 as a meaningful biomarker to both diagnose and stage melanoma. In addition, interfering with TRIB2 activity might be a therapeutic strategy for the treatment of several different tumour types.
Providing a molecular mechanism for P-glycoprotein; why would I bother?
Authors: Callaghan Richard 
Published: October 2015

It is almost 40 years since the drug efflux pump P-glycoprotein (permeability glycoprotein or P-gp) was shown to confer multi-drug resistance in cancer cells. This protein has been one of the most extensively investigated transport proteins due to its intriguing mechanism and its affect in oncology. P-gp is known to interact with over 300 compounds and the ability to achieve this has not yet been revealed. Following the binding of substrate and nucleotide, a complex series of conformational changes in the membrane and cytosolic domains translocates substrate across the membrane. Despite over 30 years of biochemical investigation, the availability of structural data and a plethora of chemical tools to modulate its function, the molecular mechanism remains a mystery. In addition, overcoming its activity in resistant cancer cells has not been achieved in the clinic, thereby garnering some degree of pessimism in the field. This review highlights the progress that has been achieved in understanding this complex protein and the value of undertaking molecular studies.
Lipid flopping in the liver
Authors: Linton Kenneth J. 
Published: October 2015

Bile is synthesized in the liver and is essential for the emulsification of dietary lipids and lipid-soluble vitamins. It is a complex mixture of amphiphilic bile acids (BAs; which act as detergent molecules), the membrane phospholipid phosphatidylcholine (PC), cholesterol and a variety of endogenous metabolites and waste products. Over the last 20 years, the combined effort of clinicians, geneticists, physiologists and biochemists has shown that each of these bile components is transported across the canalicular membrane of the hepatocyte by its own specific ATP-binding cassette (ABC) transporter. The bile salt export pump (BSEP) ABCB11 transports the BAs and drives bile flow from the liver, but it is now clear that two lipid transporters, ABCB4 (which flops PC into the bile) and the P-type ATPase ATP8B1/CDC50 (which flips a different phospholipid in the opposite direction) play equally critical roles that protect the biliary tree from the detergent activity of the bile acids. Understanding the interdependency of these lipid floppases and flippases has allowed the development of an assay to measure ABCB4 function. ABCB4 harbours numerous mis-sense mutations which probably reflects the spectrum of liver disease rooted in ABCB4 aetiology. Characterization of the effect of these mutations at the protein level opens the possibility for the development of personalized prognosis and treatment.
Far-UV phase dependence and surface characteristics of comet
67P/Churyumov-Gerasimenko as observed with Rosetta Alice
Authors: Feaga L. M. , Protopapa S. , Schindhelm R. , Stern S. A. , A’Hearn M. F. , Bertaux J.-L. , Feldman P. D. , Parker J. Wm. , Steffl A. J. , Weaver H. A. 
Published: October 2015

Aims. The Alice far-ultraviolet (FUV) spectrograph onboard Rosetta has,
for the first time, imaged the surface of a comet, 67P/Churyumov-Gerasimenko (67P), in the
FUV. With spatially resolved data, the nucleus properties are characterized in the FUV,
including phase dependence, albedo, and spectral slope. Regional measurements across the
nucleus are compared to discern any compositional variations.
Methods. Hapke theory was utilized to model the phase dependence of the
material on the surface of 67P. The phase dependence of 67P was derived from a subset of
data acquired at various phase angles in November 2014, within 50 km of the comet such
that the nucleus was spatially resolved. The derived photometric correction was then
applied to a different subset of spatially resolved data sampling several distinct
geographical regions on the nucleus acquired in August−November 2014 under similar viewing
geometries.
Results. In the FUV, the surface of 67P is dark, blue sloped, has an
average geometric albedo of 0.054±0.008 at 1475 Å near the center of the Alice bandpass, and is mostly
uniform from region to region, with the exception of the Hatmehit region, which is
slightly more reflective. These results are consistent with the suggestion made by the
Rosetta OSIRIS and VIRTIS teams that the surface of 67P is covered with a homogeneous
layer of material and that surface ice is not ubiquitous in large abundances. The modeled
Hapke parameters, specifically the single scattering albedo (w) and the asymmetry factor
(ζ), are
determined to be 0.031 ± 0.003
and −0.530 ± 0.025 near the
center of the Alice bandpass at 1475 Å. These parameters are consistent with measurements
of other comet nuclei that have been observed by flyby missions in the visible and the
near-infrared regimes.
Influence of buffer layers on Ni thin film structure and graphene growth by CVD
Authors: Ozceri Elif , Selamet Yusuf 
Published: October 2015

Abstract
Buffer and/or adhesive layers were used to decrease the dewetting of Ni thin film at graphene growth temperatures of around 900 °C. Depositing a thin buffer (Al2O3) layer onto SiO2/Si substrate significantly reduced the dewetting effect and surface roughness of Ni catalyst film. Thin adhesive (Cr) layers with or without Al2O3 buffer layers increased the texturing in (1 1 1) orientation, which was promoted by growing at an elevated temperature (450 °C). The effects of pretreatment and growth temperature on crystal orientation, grain size and surface roughness of Ni film were analyzed. Our results indicated a large positive correlation coefficient between the film thickness and surface roughness for thinner and non-buffered films, and a negative correlation coefficient between the thickness and 900 °C -annealed film roughness for thicker and buffered films. The graphene coverage was greatly improved over the films grown with Al2O3 and/or Cr layers. In summary, we suggest that growing high quality, large area, 1- or 2-layer graphene on polycrystalline Ni transition metal thin film is optimized by using Al2O3 and/or Cr layers to reduce Ni dewetting, surface roughness, and groove depth while controlling grain size and texturing in (1 1 1) orientation by annealing at 900 °C.
Identification of a Novel Mycoplasma Species in a Patient With Septic Arthritis of the Hip and Seal Finger
Authors: Westley Benjamin P. , Horazdovsky Ryan D. , Michaels Dina L. , Brown Daniel R. 
Published: October 2015

Abstract
An Alaska Native hunter developed fever, swollen finger, and septic hips after harvesting seals. Evaluation of hip tissue by 16S rRNA gene polymerase chain reaction and sequencing revealed a putative novel mycoplasma species. We report the identification of this organism and describe the first known case of disseminated seal finger mycoplasmosis.
Insights into the phenology of migration and survival of a long migrant land bird
Authors: Madon Bénédicte , Le Nuz Eric , Ferlat Cédric , Hingrat Yves 
Published: October 2015

Lay summaryFor polygamous long-migrant birds, the choice of migration strategy depends on social pressure and experience and influences the chance of survival. If you are a male, you’d better leave early in the spring to secure the best site to show off. In fall, juveniles have a hard time surviving to migration as they leave before the adults and lack experience on where to go and where to stop to rest.AbstractThe process of migration stems from an adaptation of climatic seasonality and animals have developed various strategies to complete the journey between a wintering and breeding ground. Understanding the migratory behavior and determining when and where mortality occurs during the annual cycle is fundamental to understand population dynamics and implement appropriate conservation measures. Based on a big data set and advanced statistical methods, we inspected the phenology of migration of a polygynous land bird, the Macqueen’s bustard,Chlamydotis macqueenii.We explored its migration strategies between sex, age, season and geographical origin. We show that departure for migration depended on age in the fall with juveniles being the first to leave and on age and sex in the spring with juveniles departing later and males induced to arrive early in spring to secure high-quality territories. Birds breeding at higher latitudes were the first to leave in the fall and more likely to perform longer stopovers. Bustards exhibited different strategies for spring and fall migrations: spring migration was significantly longer than fall migration with more but shorter stopovers. Survival was lower for juveniles experiencing their first migration and for all birds during fall migration and on their wintering ground. Experience linked to social hierarchical pressures and environmental conditions might be the key drivers of migration strategies and survival in long-distance polygynous migrants.
Within and among-population variation in vital rates and population dynamics in a variable environment
Authors: Vincenzi Simone , Mangel Marc , Jesensek Dusan , Garza John Carlos , Crivelli Alain J 
Published: October 2015

AbstractUnderstanding the causes of within-and among-population differences in vital rates, life histories, and population dynamics is a central topic in ecology. To understand how within-and among-population variation emerges, we need long-term studies that include episodic events and contrasting environmental conditions, data to characterize individual and shared variation, and statistical models that can tease apart population-, shared-, and individual contribution to the observed variation.We used long-term tag-recapture data and novel statistical and modeling techniques to investigate and estimate within-and among-population differences in vital rates, life histories and population dynamics of marble troutSalmo marmoratus, a endemic freshwater salmonid with a narrow range. Only ten populations of pure marble trout persist in headwaters of Alpine rivers in western Slovenia. Marble trout populations are also threatened by floods and landslides, which have caused the extinction of two populations in recent years. We estimated and determined causes of variation in growth, survival, and recruitment both within and among populations, and evaluated trade-offs between them. Specifically, we estimated the responses of these traits to variation in water temperature, density, sex, early life conditions, and the occurrence of extreme climatic events (e.g., flash floods and debris flows).We found that the effects of population density on traits were mostly limited to the early stages of life and that individual growth trajectories were established early in life. We found no clear effects of water temperature on survival and recruitment. Population density varied over time, with flash floods and debris flows causing massive mortalities and threatening population persistence. Apart from flood events, variation in population density within streams was largely determined by variation in recruitment, with survival of older fish being relatively constant over time within populations, but substantially different among populations. Marble trout show a fast-to-slow continuum of life histories, with slow growth associated with higher survival at the population level, possibly determined by food conditions and age at maturity.Our work provides unprecedented insight into the causes of variation in vital rates, life histories, and population dynamics in an endemic species that is teetering on the edge of extinction.
Association mapping of inflammatory bowel disease loci to single variant resolution
Authors: Huang Hailiang , Fang Ming , Jostins Luke , Mirkov Maša Umićević , Boucher Gabrielle , Anderson Carl A , Andersen Vibeke , Cleynen Isabelle , Cortes Adrian , Crins François , D’Amato Mauro , Deffontaine Valérie , Dimitrieva Julia , Docampo Elisa , Elansary Mahmoud , Farh Kyle Kai-How , Franke Andre , Gori Ann-Stephan , Goyette Philippe , Halfvarson Jonas , Haritunians Talin , Knight Jo , Lawrance Ian C , Lees Charlie W , Louis Edouard , Mariman Rob , Meuwissen Theo , Mni Myriam , Momozawa Yukihide , Parkes Miles , Spain Sarah L , Théâtre Emilie , Trynka Gosia , Satsangi Jack , van Sommeren Suzanne , Vermeire Severine , Xavier Ramnik J ,   International IBD Genetics Consortium, Weersma Rinse K , Duerr Richard H , Mathew Christopher G , Rioux John D , McGovern Dermot PB , Cho Judy H , Georges Michel , Daly Mark J , Barrett Jeffrey C 
Published: October 2015

SummaryInflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder that affects millions worldwide. Genome-wide association studies (GWAS) have identified 200 IBD-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 IBD loci using high-density genotyping in 67,852 individuals. Of the 139 independent associations identified in these regions, 18 were pinpointed to a single causal variant with >95% certainty, and an additional 27 associations to a single variant with >50% certainty. These 45 variants are significantly enriched for protein-coding changes (n=13), direct disruption of transcription factor binding sites (n=3) and tissue specific epigenetic marks (n=10), with the latter category showing enrichment in specific immune cells among associations stronger in CD and gut mucosa among associations stronger in UC. The results of this study suggest that high-resolution, fine-mapping in large samples can convert many GWAS discoveries into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.
Biogeographic dating of speciation times using paleogeographically informed processes
Authors: Landis Michael J. 
Published: October 2015

AbstractStandard models of molecular evolution cannot estimate absolute speciation times alone, and require external calibrations to do so. Because fossil calibration methods rely on the unreliable fossil record, most nodes in the tree of life are dated with poor accuracy. However, many major paleogeographical events are dated, and since biogeographic processes depend on paleogeographical conditions, biogeographic dating may be used as an alternative or complementary method to fossil dating. I demonstrate how a time-stratified biogeographic stochastic process may be used to estimate absolute divergence times by conditioning on dated paleogeographical events. Informed by the current paleogeographical literature, I construct an empirical dispersal graph using 25 areas and 26 epochs for the past 540 Ma of Earth’s history. Simulations indicate biogeographic dating performs well so long as paleogeography imposes constraint on biogeographic character evolution. To gauge whether biogeographic dating may have any practical use, I analyze the well-studied turtle clade (Testudines) then assess how well biogeographic dating fares compared to heavily fossil-calibrated dating results as reported in the literature. Fossil-free biogeographic dating estimated the age of the most recent common ancestor of extant turtles to be approximately 201 Ma, which is consistent with fossil-based estimates. Accuracy improves further when including a root node fossil calibration. The described model, paleogeographical dispersal graph, and analysis scripts are available for use with RevBayes.
Proactive personality and training motivation among older workers
Authors: Setti Ilaria , Dordoni Paola , Piccoli Beatrice , Bellotto Massimo , Argentero Piergiorgio 
Published: October 2015

Purpose– This paper aims at examining the relationship between proactive personality and training motivation among older workers (aged over 55 years) in a context characterized by the growing ageing of the global population. First, the authors hypothesized that proactive personality predicts the motivation to learn among older workers and that this relationship is mediated by goal orientation. In particular, the authors hypothesized that learning goal orientation may mediate the relationship between proactive personality and learning motivation.Design/methodology/approach– The employees of an Italian bank completed an online questionnaire. AMOS 17 was used to carry out confirmatory factor analysis, and the SPSS macro was used to test the meditational model.Findings– The results confirmed both the hypotheses, demonstrating the influence of proactive personality on training motivation of older workers, as mediated by goal orientation and, in particular, by learning goal orientation.Practical implications– From an applicative point of view, this study may have implications for organizations that aim to increase the employability of older people by encouraging them to undertake more training. In particular, interventions aimed at increasing learning goal orientation could contribute in strengthening proactive personality that, in turn, may affect levels of training motivation.Originality/value– Even if proactive personality has already been found as a predictor of learning motivation, to the best of the authors’ knowledge, the present study demonstrates that the relationship between proactive personality and training motivation is mediated by goal orientation among older workers.
Metallographic examination of an AISI H11 mandrel of a bridge die used in hot extrusion
Authors: Medrea Carmen , Kalfopoulos Antonios , Papageorgiou Dimitrios , Chicinas Ionel 
Published: October 2015

Purpose
– A local company producing aluminum profile encounters frequent failures to bridge dies. In total, 22 dies failed within a year, entailing production disruptions and extensive downtimes. Bridges usually exhibit cracks on the ribs. The failure analysis of the failed parts has been performed in order to propose solution for correct and economical process. The paper aims to discuss these issues.

Design/methodology/approach
– Recorded history was collected regarding tool’s material selection, manufacturing conditions, usage and service. A representative failed bridge was in depth analyzed. The piece was optically inspected. Rockwell hardness measurements and chemical analysis were performed. The paper is focussed on the microscopic examination of the failed parts. Specimens were cut from bridge’s ribs. Areas including cracks were analyzed on the cross section of the samples by optical and scanning electron microscopy. Local chemical analysis was made by X-ray microanalysis.

Findings
– Design, deficiency and improper maintenance are considered to be responsible for the systematic die damage. Prolonged preheating duration and poor quality surfaces before nitriding render dies premature unusable. The preheating duration should be controlled and protective atmosphere should be used. Furthermore, it is suggested to protect the ribs during nitriding as a preventive measure against crack initiation. The bridge’s geometry can be improved by fabricating ribs with larger radii. A finer polishing is recommended.

Originality/value
– The present analysis resolved a serious deficiency in extrusion production. Extended research has been conducted in the field of aluminum extrusion dies, nevertheless, the present work presents new metallographic aspects as well as some interesting notes regarding the repetitive nitriding of bridge dies.