bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular origin and pathophysiology of chronic lymphocytic leukemia
Authors: Seifert Marc , Sellmann Ludger , Bloehdorn Johannes , Wein Frederik , Stilgenbauer Stephan , Dürig Jan , Küppers Ralf
Published: October 2012

The cellular origin of chronic lymphocytic leukemia (CLL) is still debated, although this information is critical to understanding its pathogenesis. Transcriptome analyses of CLL and the main normal B cell subsets from human blood and spleen revealed that immunoglobulin variable region (IgV) gene unmutated CLL derives from unmutated mature CD5+ B cells and mutated CLL derives from a distinct, previously unrecognized CD5+CD27+ post–germinal center B cell subset. Stereotyped V gene rearrangements are enriched among CD5+ B cells, providing independent evidence for a CD5+ B cell derivation of CLL. Notably, these CD5+ B cell populations include oligoclonal expansions already found in young healthy adults, putatively representing an early phase in CLL development before the CLL precursor lesion monoclonal B cell lymphocytosis. Finally, we identified deregulated proteins, including EBF1 and KLF transcription factors, that were not detected in previous comparisons of CLL and conventional B cells.
FilGAP, a Rho/Rho-associated protein kinase–regulated GTPase-activating protein for Rac, controls tumor cell migration
Authors: Saito Koji , Ozawa Yuta , Hibino Keisuke , Ohta Yasutaka
Published: October 2012

Tumor cells exhibit two interconvertible modes of cell motility referred to as mesenchymal and amoeboid migration. Mesenchymal mode is characterized by elongated morphology that requires high GTPase Rac activation, whereas amoeboid mode is dependent on actomyosin contractility induced by Rho/Rho-associated protein kinase (ROCK) signaling. While elongated morphology is driven by Rac-induced protrusion at the leading edge, how Rho/ROCK signaling controls amoeboid movement is not well understood. We identified FilGAP, a Rac GTPase-activating protein (GAP), as a mediator of Rho/ROCK-dependent amoeboid movement of carcinoma cells. We show that depletion of endogenous FilGAP in carcinoma cells induced highly elongated mesenchymal morphology. Conversely, forced expression of FilGAP induced a round/amoeboid morphology that requires Rho/ROCK-dependent phosphorylation of FilGAP. Moreover, depletion of FilGAP impaired breast cancer cell invasion through extracellular matrices and reduced tumor cell extravasation in vivo. Thus phosphorylation of FilGAP by ROCK appears to promote amoeboid morphology of carcinoma cells, and FilGAP contributes to tumor invasion.
Simultaneous alignment and clustering of peptide data using a Gibbs sampling approach
Authors: Andreatta Massimo , Lund Ole , Nielsen Morten
Published: October 2012

Motivation: Proteins recognizing short peptide fragments play a central role in cellular signaling. As a result of high-throughput technologies, peptide-binding protein specificities can be studied using large peptide libraries at dramatically lower cost and time. Interpretation of such large peptide datasets, however, is a complex task, especially when the data contain multiple receptor binding motifs, and/or the motifs are found at different locations within distinct peptides.

Results: The algorithm presented in this article, based on Gibbs sampling, identifies multiple specificities in peptide data by performing two essential tasks simultaneously: alignment and clustering of peptide data. We apply the method to de-convolute binding motifs in a panel of peptide datasets with different degrees of complexity spanning from the simplest case of pre-aligned fixed-length peptides to cases of unaligned peptide datasets of variable length. Example applications described in this article include mixtures of binders to different MHC class I and class II alleles, distinct classes of ligands for SH3 domains and sub-specificities of the HLA-A*02:01 molecule.

Availability: The Gibbs clustering method is available online as a web server at http://www.cbs.dtu.dk/services/GibbsCluster.

Contact:  massimo@cbs.dtu.dk

Supplementary information:  Supplementary data are available at Bioinformatics online.
A method for integrative structure determination of protein-protein complexes
Authors: Schneidman-Duhovny Dina , Rossi Andrea , Avila-Sakar Agustin , Kim Seung Joong , Velázquez-Muriel Javier , Strop Pavel , Liang Hong , Krukenberg Kristin A. , Liao Maofu , Kim Ho Min , Sobhanifar Solmaz , Dötsch Volker , Rajpal Arvind , Pons Jaume , Agard David A. , Cheng Yifan , Sali Andrej
Published: October 2012

Motivation: Structural characterization of protein interactions is necessary for understanding and modulating biological processes. On one hand, X-ray crystallography or NMR spectroscopy provide atomic resolution structures but the data collection process is typically long and the success rate is low. On the other hand, computational methods for modeling assembly structures from individual components frequently suffer from high false-positive rate, rarely resulting in a unique solution.

Results: Here, we present a combined approach that computationally integrates data from a variety of fast and accessible experimental techniques for rapid and accurate structure determination of protein–protein complexes. The integrative method uses atomistic models of two interacting proteins and one or more datasets from five accessible experimental techniques: a small-angle X-ray scattering (SAXS) profile, 2D class average images from negative-stain electron microscopy micrographs (EM), a 3D density map from single-particle negative-stain EM, residue type content of the protein–protein interface from NMR spectroscopy and chemical cross-linking detected by mass spectrometry. The method is tested on a docking benchmark consisting of 176 known complex structures and simulated experimental data. The near-native model is the top scoring one for up to 61% of benchmark cases depending on the included experimental datasets; in comparison to 10% for standard computational docking. We also collected SAXS, 2D class average images and 3D density map from negative-stain EM to model the PCSK9 antigen–J16 Fab antibody complex, followed by validation of the model by a subsequently available X-ray crystallographic structure.

Availability:  http://salilab.org/idock

Contact:  dina@salilab.org or sali@salilab.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
Strong Genetic Differentiation Between North American and European Populations of Phytophthora alni subsp. uniformis
Authors: Aguayo Jaime , Adams Gerard C. , Halkett Fabien , Catal Mursel , Husson Claude , Nagy Zoltán Á. , Hansen Everett M. , Marçais Benoît , Frey Pascal
Published: October 2012

Alder decline caused by Phytophthora alni has been one of the most important diseases of natural ecosystems in Europe during the last 20 years. The emergence of P. alni subsp. alni —the pathogen responsible for the epidemic—is linked to an interspecific hybridization event between two parental species: P. alni subsp. multiformis and P. alni subsp. uniformis. One of the parental species, P. alni subsp. uniformis, has been isolated in several European countries and, recently, in North America. The objective of this work was to assess the level of genetic diversity, the population genetic structure, and the putative reproduction mode and mating system of P. alni subsp. uniformis. Five new polymorphic microsatellite markers were used to contrast both geographical populations. The study comprised 71 isolates of P. alni subsp. uniformis collected from eight European countries and 10 locations in North America. Our results revealed strong differences between continental populations (Fst = 0.88; Rst = 0.74), with no evidence for gene flow. European isolates showed extremely low genetic diversity compared with the North American collection. Selfing appears to be the predominant mating system in both continental collections. The results suggest that the European P. alni subsp. uniformis population is most likely alien and derives from the introduction of a few individuals, whereas the North American population probably is an indigenous population.
Combined Use of Two Biocontrol Agents with Different Biocontrol Mechanisms Most Likely Results in Less Than Expected Efficacy in Controlling Foliar Pathogens Under Fluctuating Conditions: A Modeling Study
Authors: Xu X.-M. , Jeger M. J.
Published: October 2012

Effective use of biocontrol agents (BCAs) is a potentially important component of sustainable agriculture; recently, there has been a trend for combined use of several BCAs, with an expectation of synergistic interactions among them. A previous numerical study suggested that, under homogenous conditions in which two BCAs occupied the same host tissue as the pathogen, combined use of two BCAs with different biocontrol mechanisms resulted, in most cases, in efficacies similar to using the more efficacious one alone; this result is consistent with published experimental results. The present study investigates whether combined use of a mycoparasitic and a competitive BCA leads to greater efficacy than that expected when the model is modified to allow for fluctuating temperature regimes and the effects of temperature on the pathogen and BCAs. Within the range of parameter values considered, combined use of two BCAs is shown to be less effective than that expected under the assumption of Bliss independence, and to result in a level of efficacy similar to that achieved by the more efficacious component used alone, indicating antagonistic interactions between the two BCAs. Nevertheless, combined use of two BCAs resulted in a slightly longer delay in epidemic development than did individual use of BCAs. Stochastic variability in simulated hourly temperatures did not result in a high level of variability in efficacy among replicates; nevertheless, the among-replicate variability appeared to be greater for the combined use of BCAs than for individual BCAs used alone. In contrast, there were greater effects of varying BCA–temperature relationships and application time (reflected in the temperature profile) on efficacy, suggesting the importance of characterizing the relationship between BCA activity and environmental conditions in future research.
United States Anesthesiologists over 50
Authors: Orkin Fredrick K. , McGinnis Sandra L. , Forte Gaetano J. , Peterson Mary Dale , Schubert Armin , Katz Jonathan D. , Berry Arnold J. , Cohen Norman A. , Holzman Robert S. , Jackson Stephen H. , Martin Donald E. , Garfield Joseph M.
Published: October 2012

Background

Anesthesiology is among the medical specialties expected to have physician shortage. With little known about older anesthesiologists' work effort and retirement decision making, the American Society of Anesthesiologists participated in a 2006 national survey of physicians aged 50-79 yr.

Methods

Samples of anesthesiologists and other specialists completed a survey of work activities, professional satisfaction, self-defined health and financial status, retirement plans and perspectives, and demographics. A complex survey design enabled adjustments for sampling and response-rate biases so that respondents' characteristics resembled those in the American Medical Association Physician Masterfile. Retirement decision making was modeled with multivariable ordinal logistic regression. Life-table analysis provided a forecast of likely clinical workforce trends over an ensuing 30 yr.

Results

Anesthesiologists (N = 3,222; response rate = 37%) reported a mean work week of 49.4 h and a mean retirement age of 62.7 yr, both values similar to those of other older physicians. Work week decreased with age, and part-time work increased. Women worked a shorter work week (mean, 47.9 vs. 49.7 h, P = 0.024), partly due to greater part-time work (20.2 vs. 13.1%, P value less than 0.001). Relative importance of factors reported among those leaving patient care differed by age cohort, subspecialty, and work status. Poor health was cited by 64% of anesthesiologists retiring in their 50s as compared with 43% of those retiring later (P = 0.039).

Conclusions

This survey lends support for greater attention to potentially modifiable factors, such as workplace wellness and professional satisfaction, to prevent premature retirement. The growing trend in part-time work deserves further study.
Evolutionary rescue of a green alga kept in the dark
Authors: Bell Graham
Published: October 2012

Chlamydomonas
(Chlorophyta) can grow as a heterotroph on medium supplemented with acetate in the dark. A long-term experiment to investigate adaptation to dark conditions was set up with hundreds of replicate lines. Growth was initially slow, and most lines became extinct when transferred every few weeks. Some lines survived through the expansion of lineages derived from cells with extreme phenotypes and exhibited a U-shaped curve of collapse and recovery. Two short-term experiments were set up to evaluate the effect of sex on the frequency of ‘evolutionary rescue’ by deriving replicate lines from ancestral populations with contrasting sexual histories that had been cultured in the light for hundreds of generations. When transferred to dark conditions of growth, lines derived from obligately sexual populations survived more often than lines derived from facultatively sexual or asexual populations. This reflected the higher initial frequency of cells able to grow in the dark, due to greater genetic diversity supported by sexual fusion and recombination. The greater probability of evolutionary rescue suggests a general reason for the prevalence of sexual species.
Nestling erythrocyte resistance to oxidative stress predicts fledging success but not local recruitment in a wild bird
Authors: Losdat Sylvain , Helfenstein Fabrice , Blount Jonathan D. , Marri Viviana , Maronde Lea , Richner Heinz
Published: October 2012

Stressful conditions experienced by individuals during their early development have long-term consequences on various life-history traits such as survival until first reproduction. Oxidative stress has been shown to affect various fitness-related traits and to influence key evolutionary trade-offs but whether an individual's ability to resist oxidative stress in early life affects its survival has rarely been tested. In the present study, we used four years of data obtained from a free-living great tit population (Parus major;n= 1658 offspring) to test whether pre-fledging resistance to oxidative stress, measured as erythrocyte resistance to oxidative stress and oxidative damage to lipids, predicted fledging success and local recruitment. Fledging success and local recruitment, both major correlates of survival, were primarily influenced by offspring body mass prior to fledging. We found that pre-fledging erythrocyte resistance to oxidative stress predicted fledging success, suggesting that individual resistance to oxidative stress is related to short-term survival. However, local recruitment was not influenced by pre-fledging erythrocyte resistance to oxidative stress or oxidative damage. Our results suggest that an individual ability to resist oxidative stress at the offspring stage predicts short-term survival but does not influence survival later in life.
Bactericidal strontium-releasing injectable bone cements based on bioactive glasses
Authors: Brauer Delia S. , Karpukhina Natalia , Kedia Gopal , Bhat Aditya , Law Robert V. , Radecka Izabela , Hill Robert G.
Published: October 2012

Strontium-releasing injectable bone cements may have the potential to prevent implant-related infections through the bactericidal action of strontium, while enhancing bone formation in patients suffering from osteoporosis. A melt-derived bioactive glass (BG) series (SiO
2
–CaO–CaF
2
–MgO) with 0–50% of calcium substituted with strontium on a molar base were produced. By mixing glass powder, poly(acrylic acid) and water, cements were obtained which can be delivered by injection and set
in situ
, giving compressive strength of up to 35 MPa. Strontium release was dependent on BG composition with increasing strontium substitution resulting in higher concentrations in the medium. Bactericidal effects were tested on
Staphylococcus aureus
and
Streptococcus faecalis
; cell counts were reduced by up to three orders of magnitude over 6 days. Results show that bactericidal action can be increased through BG strontium substitution, allowing for the design of novel antimicrobial and bone enhancing cements for use in vertebroplasty or kyphoplasty for treating osteoporosis-related vertebral compression fractures.
Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds
Authors: Rahman Mona N. , Vukomanovic Dragic , Vlahakis Jason Z. , Szarek Walter A. , Nakatsu Kanji , Jia Zongchao
Published: October 2012

The development of heme oxygenase (HO) inhibitors, especially those that are isozyme-selective, promises powerful pharmacological tools to elucidate the regulatory characteristics of the HO system. It is already known that HO has cytoprotective properties and may play a role in several disease states, making it an enticing therapeutic target. Traditionally, the metalloporphyrins have been used as competitive HO inhibitors owing to their structural similarity with the substrate, heme. However, given heme's important role in several other proteins (e.g. cytochromes P450, nitric oxide synthase), non-selectivity is an unfortunate side-effect. Reports that azalanstat and other non-porphyrin molecules inhibited HO led to a multi-faceted effort to develop novel compounds as potent, selective inhibitors of HO. This resulted in the creation of non-competitive inhibitors with selectivity for HO, including a subset with isozyme selectivity for HO-1. Using X-ray crystallography, the structures of several complexes of HO-1 with novel inhibitors have been elucidated, which provided insightful information regarding the salient features required for inhibitor binding. This included the structural basis for non-competitive inhibition, flexibility and adaptability of the inhibitor binding pocket, and multiple, potential interaction subsites, all of which can be exploited in future drug-design strategies.
Increased longevity evolves from grandmothering
Authors: Kim Peter S. , Coxworth James E. , Hawkes Kristen
Published: October 2012

Postmenopausal longevity may have evolved in our lineage when ancestral grandmothers subsidized their daughters' fertility by provisioning grandchildren, but the verbal hypothesis has lacked mathematical support until now. Here, we present a formal simulation in which life spans similar to those of modern chimpanzees lengthen into the modern human range as a consequence of grandmother effects. Greater longevity raises the chance of living through the fertile years but is opposed by costs that differ for the sexes. Our grandmother assumptions are restrictive. Only females who are no longer fertile themselves are eligible, and female fertility extends to age 45 years. Initially, there are very few eligible grandmothers and effects are small. Grandmothers can support only one dependent at a time and do not care selectively for their daughters' offspring. They must take the oldest juveniles still relying on mothers; and infants under the age of 2 years are never eligible for subsidy. Our model includes no assumptions about brains, learning or pair bonds. Grandmother effects alone are sufficient to propel the doubling of life spans in less than sixty thousand years.
Long-term differences in extinction risk among the seven forms of rarity
Authors: Harnik Paul G. , Simpson Carl , Payne Jonathan L.
Published: October 2012

Rarity is widely used to predict the vulnerability of species to extinction. Species can be rare in markedly different ways, but the relative impacts of these different forms of rarity on extinction risk are poorly known and cannot be determined through observations of species that are not yet extinct. The fossil record provides a valuable archive with which we can directly determine which aspects of rarity lead to the greatest risk. Previous palaeontological analyses confirm that rarity is associated with extinction risk, but the relative contributions of different types of rarity to extinction risk remain unknown because their impacts have never been examined simultaneously. Here, we analyse a global database of fossil marine animals spanning the past 500 million years, examining differential extinction with respect to multiple rarity types within each geological stage. We observe systematic differences in extinction risk over time among marine genera classified according to their rarity. Geographic range played a primary role in determining extinction, and habitat breadth a secondary role, whereas local abundance had little effect. These results suggest that current reductions in geographic range size will lead to pronounced increases in long-term extinction risk even if local populations are relatively large at present.
An end to insight? New Caledonian crows can spontaneously solve problems without planning their actions
Authors: Taylor Alex H. , Knaebe Brenna , Gray Russell D.
Published: October 2012

Animals rarely solve problems spontaneously. Some bird species, however, can immediately find a solution to the string-pulling problem. They are able to rapidly gain access to food hung on the end of a long string by repeatedly pulling and then stepping on the string. It is currently unclear whether these spontaneous solutions are produced by insight or by a perceptual-motor feedback loop. Here, we presented New Caledonian crows and humans with a novel horizontal string-pulling task. While the humans succeeded, no individual crow showed a significant preference for the connected string, and all but one failed to gain the food even once. These results clearly show that string pulling in New Caledonian crows is generated not by insight, but by perceptual feedback. Animals can spontaneously solve problems without planning their actions.
Cost of reproduction in the Queensland fruit fly: Y-model versus lethal protein hypothesis
Authors: Fanson Benjamin G. , Fanson Kerry V. , Taylor Phillip W.
Published: October 2012

The trade-off between lifespan and reproduction is commonly explained by differential allocation of limited resources. Recent research has shown that the ratio of protein to carbohydrate (P : C) of a fly's diet mediates the lifespan–reproduction trade-off, with higher P : C diets increasing egg production but decreasing lifespan. To test whether this P : C effect is because of changing allocation strategies (Y-model hypothesis) or detrimental effects of protein ingestion on lifespan (lethal protein hypothesis), we measured lifespan and egg production in Queensland fruit flies varying in reproductive status (mated, virgin and sterilized females, virgin males) that were fed one of 18 diets varying in protein and carbohydrate amounts. The Y-model predicts that for sterilized females and for males, which require little protein for reproduction, there will be no effect of P : C ratio on lifespan; the lethal protein hypothesis predicts that the effect of P : C ratio should be similar in all groups. In support of the lethal protein hypothesis, and counter to the Y-model, the P : C ratio of the ingested diets had similar effects for all groups. We conclude that the trade-off between lifespan and reproduction is mediated by the detrimental side-effects of protein ingestion on lifespan.
Eye shape and the nocturnal bottleneck of mammals
Authors: Hall Margaret I. , Kamilar Jason M. , Kirk E. Christopher
Published: October 2012

Most vertebrate groups exhibit eye shapes that vary predictably with activity pattern. Nocturnal vertebrates typically have large corneas relative to eye size as an adaptation for increased visual sensitivity. Conversely, diurnal vertebrates generally demonstrate smaller corneas relative to eye size as an adaptation for increased visual acuity. By contrast, several studies have concluded that many mammals exhibit typical nocturnal eye shapes, regardless of activity pattern. However, a recent study has argued that new statistical methods allow eye shape to accurately predict activity patterns of mammals, including cathemeral species (animals that are equally likely to be awake and active at any time of day or night). Here, we conduct a detailed analysis of eye shape and activity pattern in mammals, using a broad comparative sample of 266 species. We find that the eye shapes of cathemeral mammals completely overlap with nocturnal and diurnal species. Additionally, most diurnal and cathemeral mammals have eye shapes that are most similar to those of nocturnal birds and lizards. The only mammalian clade that diverges from this pattern is anthropoids, which have convergently evolved eye shapes similar to those of diurnal birds and lizards. Our results provide additional evidence for a nocturnal ‘bottleneck’ in the early evolution of crown mammals.
The genomics of adaptation
Authors: Radwan Jacek , Babik Wiesław
Published: October 2012

The amount and nature of genetic variation available to natural selection affect the rate, course and outcome of evolution. Consequently, the study of the genetic basis of adaptive evolutionary change has occupied biologists for decades, but progress has been hampered by the lack of resolution and the absence of a genome-level perspective. Technological advances in recent years should now allow us to answer many long-standing questions about the nature of adaptation. The data gathered so far are beginning to challenge some widespread views of the way in which natural selection operates at the genomic level. Papers in this Special Feature of Proceedings of the Royal Society B illustrate various aspects of the broad field of adaptation genomics. This introductory article sets up a context and, on the basis of a few selected examples, discusses how genomic data can advance our understanding of the process of adaptation.
The Effects ofα-Lipoic Acid against Testicular Ischemia-Reperfusion Injury in Rats
Authors: Ozbal Seda , Ergur Bekir Ugur , Erbil Guven , Tekmen Isıl , Bagrıyanık Alper , Cavdar Zahide
Published: October 2012

Testicular torsion is one of the urologic emergencies occurring frequently in neonatal and adolescent period. Testis is sensitive to ischemia-reperfusion injury, and, therefore, ischemia and consecutive reperfusion cause an enhanced formation of reactive oxygen species that result in testicular cell damage and apoptosis.α-lipoic acid is a free radical scavenger and a biological antioxidant. It is widely used in the prevention of oxidative stress and cellular damage. We aimed to investigate the protective effect ofα-lipoic acid on testicular damage in rats subjected to testicular ischemia-reperfusion injury. 35 rats were randomly divided into 5 groups: control, sham operated, ischemia, ischemia-reperfusion, and ischemia-reperfusion +lipoic acid groups, 2 h torsion and 2 h detorsion of the testis were performed. Testicular cell damage was examined by H-E staining. TUNEL and active caspase-3 immunostaining were used to detect germ cell apoptosis. GPx , SOD activity, and MDA levels were evaluated. Histological evaluation showed thatα-lipoic acid pretreatment reduced testicular cell damage and decreased TUNEL and caspase-3-positive cells. Additionally,α-lipoic acid administration decreased the GPx and SOD activity and increased the MDA levels. The present results suggest that LA is a potentially beneficial agent in protecting testicular I/R in rats.
Dynamic Changes in the Distribution of Minerals in Relation to Phytic Acid Accumulation during Rice Seed Development
Authors: Iwai Toru , Takahashi Michiko , Oda Koshiro , Terada Yasuko , Yoshida Kaoru T.
Published: October 2012

Phytic acid (inositol hexakisphosphate [InsP6]) is the storage compound of phosphorus in seeds. As phytic acid binds strongly to metallic cations, it also acts as a storage compound of metals. To understand the mechanisms underlying metal accumulation and localization in relation to phytic acid storage, we applied synchrotron-based x-ray microfluorescence imaging analysis to characterize the simultaneous subcellular distribution of some mineral elements (phosphorus, calcium, potassium, iron, zinc, and copper) in immature and mature rice (Oryza sativa) seeds. This fine-imaging method can reveal whether these elements colocalize. We also determined their accumulation patterns and the changes in phosphate and InsP6 contents during seed development. While the InsP6 content in the outer parts of seeds rapidly increased during seed development, the phosphate contents of both the outer and inner parts of seeds remained low. Phosphorus, calcium, potassium, and iron were most abundant in the aleurone layer, and they colocalized throughout seed development. Zinc was broadly distributed from the aleurone layer to the inner endosperm. Copper localized outside the aleurone layer and did not colocalize with phosphorus. From these results, we suggest that phosphorus translocated from source organs was immediately converted to InsP6 and accumulated in aleurone layer cells and that calcium, potassium, and iron accumulated as phytic acid salt (phytate) in the aleurone layer, whereas zinc bound loosely to InsP6 and accumulated not only in phytate but also in another storage form. Copper accumulated in the endosperm and may exhibit a storage form other than phytate.
An introduction to three-dimensional X-ray diffraction microscopy
Authors: Poulsen Henning Friis
Published: October 2012

Three-dimensional X-ray diffraction microscopy is a fast and nondestructive structural characterization technique aimed at studies of the individual crystalline elements (grains or subgrains) within millimetre-sized polycrystalline specimens. It is based on two principles: the use of highly penetrating hard X-rays from a synchrotron source and the application of `tomographic' reconstruction algorithms for the analysis of the diffraction data. In favourable cases, the position, morphology, phase and crystallographic orientation can be derived for up to 1000 elements simultaneously. For each grain its average strain tensor may also be derived, from which the type II stresses can be inferred. Furthermore, the dynamics of the individual elements can be monitored during typical processes such as deformation or annealing. A review of the field is provided, with a viewpoint from materials science.
Three-dimensional plastic response in polycrystalline coppervianear-field high-energy X-ray diffraction microscopy
Authors: Li S. F. , Lind J. , Hefferan C. M. , Pokharel R. , Lienert U. , Rollett A. D. , Suter R. M.
Published: October 2012

The evolution of the crystallographic orientation field in a polycrystalline sample of copper is mapped in three dimensions as tensile strain is applied. Using forward-modeling analysis of high-energy X-ray diffraction microscopy data collected at the Advanced Photon Source, the ability to track intragranular orientation variations is demonstrated on an ∼2 µm length scale with ∼0.1° orientation precision. Lattice rotations within grains are tracked between states with ∼1° precision. Detailed analysis is presented for a sample cross section before and after ∼6% strain. The voxel-based (0.625 µm triangular mesh) reconstructed structure is used to calculate kernel-averaged misorientation maps, which exhibit complex patterns. Simulated scattering from the reconstructed orientation field is shown to reproduce complex scattering patterns generated by the defected microstructure. Spatial variation of a goodness-of-fit or confidence metric associated with the optimized orientation field indicates regions of relatively high or low orientational disorder. An alignment procedure is used to match sample cross sections in the different strain states. The data and analysis methods point toward the ability to perform detailed comparisons between polycrystal plasticity computational model predictions and experimental observations of macroscopic volumes of material.
On the use of modification functions when Fourier transforming total scattering data
Authors: Soper Alan K. , Barney Emma R.
Published: October 2012

When Fourier transforming radiation total scattering data to the pair distribution function it is common to use a `modification' function to help reduce the termination ripples that would otherwise occur as a result of the finite range and counting statistics of the scattering data. One of the most common functions employed was proposed by Lorch [J. Phys. C Solid State Phys.(1969),2, 229–237]. In a recent article [Soper & Barney (2011).J. Appl. Cryst.44, 714–726] a revised version of this function was proposed. Here the effectiveness of these two functions at removing spurious structure from Fourier transformed data is compared. It is found that the two functions produce equivalent results, unless the broadening is allowed to increase withr, in which case the revised Lorch function is better at suppressing spurious oscillations. The presence of counting statistics produces a marked increase in the amplitude of the truncation oscillations.
Experimental analysis of overall thermal properties of Nd:La2CaB10O19crystals
Authors: Zhang Jianxiu , Wu Yang , Zhang Guochun , Li Yin , Wu Yicheng
Published: October 2012

Pure or rare-earth-ion-doped La2CaB10O19(LCB) is a promising optical material for nonlinear frequency conversion, laser and self-frequency doubling applications. In this paper, the thermophysical properties of Nd3+-doped LCB (Nd:LCB) crystals were measured and compared with those of pure and of Yb3+- and Er3+-doped LCB, as well as other borate nonlinear optical crystals. The melting points of rare-earth-doped LCB crystals are lower than that of pure LCB. Thermal expansion coefficients along thea,b,c,c*,a*, 〈110〉 and 〈110〉* directions have been measured, and the principal expansion coefficients were calculated to be 1.85 × 10−6, 4.13 × 10−6and 8.79 × 10−6 K−1. The measured specific heat of Nd:LCB is lower than that of pure LCB, resulting in a larger internal temperature gradient under irradiation by a pulsed laser beam. The measured thermal expansion anisotropy of Nd:LCB is stronger than that of pure LCB. The thermal conductivities of Nd:LCB along thecandc* directions are smaller than those along other crystallographic directions.
Genetic identification of Iberian rodent species using both mitochondrial and nuclear loci: application to noninvasive sampling
Authors: Barbosa S. , Pauperio J. , Searle J. B. , Alves P. C.
Published: October 2012

Species identification through noninvasive sampling is increasingly used in animal conservation genetics, given that it obviates the need to handle free‐living individuals. Noninvasive sampling is particularly valuable for elusive and small species such as rodents. Although rodents are not usually assumed to be the most obvious target for conservation, of the 21 species or near‐species present in Iberia, three are considered endangered and declining, while several others are poorly studied. Here, we develop a genetic tool for identifying all rodent species in Iberia by noninvasive genetic sampling. To achieve this purpose, we selected one mitochondrial gene [cytochrome b (cyt‐b)] and one nuclear gene [interphotoreceptor retinoid‐binding protein (IRBP)], which we first sequenced using tissue samples. Both genes allow for the phylogenetic distinction of all species except the sibling species Microtus lusitanicus and Microtus duodecimcostatus. Overall, cyt‐b showed higher resolution than IRBP, revealing a clear barcoding gap. To allow these markers to be applied to noninvasive samples, we selected a short highly diagnostic fragment from each gene, which we used to obtain sequences from faeces and bones from owl pellets. Amplification success for the cyt‐b and IRBP fragment was 85% and 43% in faecal and 88% and 64% in owl‐pellet DNA extractions, respectively. The method allows the unambiguous identification of the great majority of Iberian rodent species from noninvasive samples, with application in studies of distribution, spatial ecology and population dynamics, and for conservation.
Two faces of microbiota in inflammatory and autoimmune diseases: triggers and drugs
Authors: Kverka Miloslav , Tlaskalova‐Hogenova Helena
Published: October 2012

The prevalence of chronic autoimmune and inflammatory diseases, such as inflammatory bowel disease, allergies, or rheumatic diseases, is steadily increasing in developed countries. This increase is probably accelerated by environmental factors, such as decrease in infectious burden or changes in food processing. These lifestyle changes then strongly influence the strongest stimulus for the immune system – commensal microbiota. Despite the differences in the affected organ, the immune‐mediated diseases have one or more factors in common – microbe either as a trigger or as a protector, mucosal barrier dysfunction, and dysregulation of the immune system. The core questions, which microbes are involved and how these diseases can be cured or even prevented still remain unsolved. Powered by the recent progress in technology, by new insights into the function of immune system, by advances in microbiome research, and extended use of gnotobiological techniques, these mechanisms are now being unravelled and new therapeutic possibilities are emerging. To secure their niche, the microbes devised many ingenious ways, how to dampen the inflammation. Nonpathogenic microorganisms or microbial components isolated from probiotic, commensal or even pathogenic microbes could be, therefore, used to interfere with the pathogenetic mechanisms of immune‐mediated diseases.
School motivation and high school dropout: The mediating role of educational expectation
Authors: Fan Weihua , Wolters Christopher A.
Published: October 2012

Background

A good deal of evidence indicates that students' motivational beliefs and attitudes play a critical role in their academic success. Research studies on how motivational factors may help determine whether students remain in high school or drop out, however, are relatively few. More specifically, there is a lack of research examining the dynamics of whether students' motivational beliefs from earlier in high school might be used to predict their status as a dropout in their final year.

Aims

The aim of the present study was to examine the mediating role of students' educational expectations in linking students' school motivation to their dropout status by utilizing a nationally representative dataset.

Sample

The present study used data from the Educational Longitudinal Study of 2002 (ELS: 2002). The final sample consisted of 16,194 students, with approximately 54% White, 13% Black, 16% Hispanic, and 10% Asian students, and the rest were Native American, Hawaiian, multiracial, or of other races.

Method

Structural equation modelling was employed to conduct the mediational analysis.

Results

The results of the present study demonstrated that the relationships between student ability beliefs in math and English and student behaviour of dropping out were fully mediated by students' educational expectations. The results also revealed that student intrinsic value in math and English had significant indirect relations with student behaviour of leaving school through students' educational expectations.

Conclusions

The results of this study suggest that explanations for student dropout status that rely solely on students' social background and school behaviours without considering their motivation are incomplete. The study expands the extant research by showing possible pathways that motivate students to persist in high school. These pathways are specifically rooted in students' ability beliefs and intrinsic interest in learning through their relationships with students' expectations for their education.
Social support and trait personality are independently associated with resting cardiovascular function in women
Authors: Creaven Ann‐Marie , Howard Siobhán , Hughes Brian M.
Published: October 2012

Objectives

Social support is thought to positively influence appraisals of stressors and coping resources, thereby attenuating the harmful effects of stress. Notably, perceived available support (rather than actually received support) is believed to benefit well‐being independent of the sense of obligation or threats to self‐esteem that receiving support may entail. This study examined whether perceived support levels were associated with reduced cardiovascular levels, an important predictor of cardiovascular disease risk, independent of broad trait personality variables frequently reported to overlap with perceived support. In doing so, we sought to determine whether the effects of perceived support are independent of links between personality and social support.

Design

A cross‐sectional design was employed.

Methods

Resting cardiovascular levels were measured using a Finometer in a sample of healthy women (N = 145). The Short‐Form Social Support Questionnaire and the Revised Eysenck's Personality Questionnaire were used to assess support levels and personality. Regression was used to compare associations with psychometric indices of support (namely, perceived network size and perceived satisfaction with support) and personality (psychoticism, extraversion and neuroticism).

Results

Support independently predicted systolic blood pressure (SBP; p = .03) and HR (p = .02) when personality was controlled for, while personality also predicted SBP (p = .01) and DBP (p = .02). Support effects were not mediated by personality.

Conclusions

The findings corroborate previous research indicating links between support and resting cardiovascular levels and additionally demonstrate these to be independent of associations between support and personality.

Statement of contribution

What is already known on this subject? Social support is known to have several physical health benefits particularly for cardiovascular function. Studies have demonstrated psychometrically assessed support to predict reduced resting cardiovascular levels. Other work links support significantly with trait personality, particularly extraversion and neuroticism.

What does this study add? Corroborating previous studies, social support was associated with reduced systolic blood pressure and heart rate. Importantly, these results remained robust to controlling for trait personality. The effects of support on cardiovascular levels are independent of personality influences on social support levels.
Pharmacophore‐Based Drug Design and Biological Evaluation of Novel ABCB1 Inhibitors
Authors: Zhang Sheng‐lie , Wei Yin‐xiang , Li Qian , Sun Hao‐peng , Peng Hui , You Qi‐dong
Published: October 2012

Overexpression of ABCB1 is one of major barriers for multidrug resistance in chemotherapy and limits drug oral bioavailability. Inhibition of ABCB1 would sensitize multidrug resistance in clinical cancer chemotherapy. With this aim, a 3D pharmacophore model was created based on known ABCB1 inhibitors with correlation coefficient of 0.94, comprising three hydrophobic features and one hydrogen bond acceptor. It was further validated and used to search our in‐house 3D database for potential ABCB1 inhibitors. The inhibitory activities of the best hits were evaluated by several biological assays, such as rhodamine 123 accumulation assay, chemosensitization assay, multidrug resistance 1‐Madin‐Darby canine kidney cells/Madin‐Darby canine kidney cells permeability assay. Finally, compounds YZ‐3 and YZ‐16 were identified as potential leads to be developed in the designing of novel potent ABCB1 inhibitors.
Dynamic Change of Heme Environment in Soluble Guanylate Cyclase and Complexation of NO‐Independent Drug Agents with H‐NOX Domain
Authors: Alisaraie Laleh , Fu Yangxin , Tuszynski Jack A.
Published: October 2012

Soluble guanylate cyclase is a heterodimer receptor that functions in several signal transduction pathways. Conversion of guanosine 5′‐triphosphate to 3′,5′‐cyclic monophosphate second messenger at the catalytic domain is regulated by the changes at heme nitric oxide/oxygen domain of the β‐subunit. To better understand conformational changes at heme site that may impact on activities of catalytic domain, three soluble guanylate cyclase homolog proteins with heme at Fe‐His state were investigated, and their dynamic behaviors were monitored in both unliganded (apo) and complex with heme. As a result of dynamic conformational changes, Lys110, Asp45, Arg135, and Glu41 were found interacting with the site gate, which may interfere with transportation of small molecules in and out of the heme site. An alternative binding site adjacent to that of heme was identified. Binding affinity of several nitric oxide‐independent activators and heme‐dependent stimulators was examined, and their binding modes in the heme site and in the alternative binding site in the human soluble guanylate cyclase enzyme were computationally simulated. The calculated binding energies were used as criteria to filter results of virtual high‐throughput screenings based on FlexX ligand–docking algorithm and absorption, distribution, metabolism, excretion, and toxicity properties on databases of available drugs. The identified drugs from virtual high‐throughput screening have been suggested for experimental investigations, based on which they may either be directly repurposed or require structural modifications for better physico‐chemical and pharmacological properties.
Defining the impact of individual sample variability on routine immunoassay of serum free light chains (sFLC) in multiple myeloma
Authors: Murng S H K , Follows L , Whitfield P , Snowden J A , Swallow K , Green K , Sargur R , Egner W
Published: October 2012

Serum free light chain (sFLC) measurement has gained widespread acceptance and is incorporated into various diagnostic and response criteria. Non-linearity and antigen excess are the main causes of ‘variability’ in the measurement of sFLC using immunoassay, but the impact of these on measurement has been unclear. We performed a retrospective evaluation using a dilutional strategy to detect these phenomena. A total of 464 samples in 2009 and 373 samples in 2010 were analysed for sFLC. Non-linearity was detected in both high and apparently normal sFLC. Major non-linearity of more than twofold is common in high kappa (20·2%) and lambda (14·1%). It is less common in samples with apparently normal levels – kappa (6·4%) and lambda (9·5%). 9·4% of kappa and 15·5% of lambda showed antigen excess at screening dilutions. 34·4% of the samples had either non-linearity or antigen excess. We conclude that significant measurement variability is common in the measurement of sFLC. There is currently no reliable technique to detect non-linearity phenomena unless a serial dilution strategy is applied to every analysis. We recommend that laboratories routinely reporting sFLC results for clinical services need appropriate strategies for addressing these issues. Clinicians should be aware of these limitations in interpretation of sFLC assay for individual patients. Future guidelines should adopt action thresholds which are grounded firmly in test performance parameters.