bluuebunny/crossref_metadata_2025 huggingface dataset:
FKBPs facilitate the termination of spontaneous Ca2+ release in wild-type RyR2 but not CPVT mutant RyR2
Authors: Zhang Joe Z. , Waddell Helen M.M. , Wu Ella , Dholakia Jhanvi , Okolo Chidinma A. , McLay Janet C. , Jones Peter P.
Published: May 2016

FK506-binding proteins 12.6 (FKBP12.6) and 12 (FKBP12) tightly associate with the cardiac ryanodine receptor (RyR2). Studies suggest that dissociation of FKBP12.6 from mutant forms of RyR2 contributes to store overload-induced Ca2+ release (SOICR) and Ca2+-triggered arrhythmias. However, these findings are controversial. Previous studies focused on the effect of FKBP12.6 on the initiation of SOICR and did not explore changes in the termination of Ca2+ release. Less is known about FKBP12. We aimed to determine the effect of FKBP12.6 and FKBP12 on the termination of SOICR. Using single-cell imaging, in cells expressing wild-type RyR2, we found that FKBP12.6 and FKBP12 significantly increase the termination threshold of SOICR without changing the activation threshold of SOICR. This effect, dependent on the association of each FKBP with RyR2, reduced the magnitude of Ca2+ release but had no effect on the propensity for SOICR. In contrast, neither FKBP12.6 nor FKBP12 was able to regulate an arrhythmogenic variant of RyR2, despite a conserved protein interaction. Our results suggest that both FKBP12.6 and FKBP12 play critical roles in regulating RyR2 function by facilitating the termination of SOICR. The inability of FKBPs to mediate a similar effect on the mutant RyR2 represents a novel mechanism by which mutations within RyR2 lead to arrhythmia.
SNARE zippering
Authors: Lou Xiaochu , Shin Yeon-Kyun
Published: May 2016

SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins are a highly conserved set of membrane-associated proteins that mediate intracellular membrane fusion. Cognate SNAREs from two separate membranes zipper to facilitate membrane apposition and fusion. Though the stable post-fusion conformation of SNARE complex has been extensively studied with biochemical and biophysical means, the pathway of SNARE zippering has been elusive. In this review, we describe some recent progress in understanding the pathway of SNARE zippering. We particularly focus on the half-zippered intermediate, which is most likely to serve as the main point of regulation by the auxiliary factors.
Modeling crossed-beam energy transfer for inertial confinement fusion
Authors: Marion D. J. Y. , Debayle A. , Masson-Laborde P.-E. , Loiseau P. , Casanova M.
Published: May 2016

We developed a numerical code that describes both the energy transfer occurring when two or more laser beams overlap in a weakly non-homogeneous plasma, and the beam energy losses associated with the electron-ion collisions. The numerical solutions are validated with both the exact analytical solutions in homogeneous plasmas, and with new approximate analytical solutions in non-homogeneous plasmas that include the aforementioned inverse bremsstrahlung effect. Comparisons with kinetic particle-in-cell simulations are satisfactory, provided the acoustic wave-breaking limit and the self-focusing regime are not reached. An application of the Cross-Beam Energy Transfer model is shown for a typical case of indirect-drive implosion in a gold hohlraum.
Evaluation of thermal helium beam and line-ratio fast diagnostic on the National Spherical Torus Experiment-Upgrade
Authors: Muñoz Burgos J. M. , Agostini M. , Scarin P. , Stotler D. P. , Unterberg E. A. , Loch S. D. , Schmitz O. , Tritz K. , Stutman D.
Published: May 2016

A 1-D kinetic collisional radiative model with state-of-the-art atomic data is developed and employed to simulate line emission to evaluate the Thermal Helium Beam (THB) diagnostic on NSTX-U. This diagnostic is currently in operation on RFX-mod, and it is proposed to be installed on NSTX-U. The THB system uses the intensity ratios of neutral helium lines 667.8, 706.5, and 728.1 nm to derive electron temperature (eV) and density (cm−3) profiles. The purpose of the present analysis is to evaluate the applications of this diagnostic for determining fast (∽4 μs) electron temperature and density radial profiles on the scrape-off layer and edge regions of NSTX-U that are needed in turbulence studies. The diagnostic is limited by the level of detection of the 728.1 nm line, which is the weakest of the three. This study will also aid in future design of a similar 2-D diagnostic system on the divertor.
Information capacity of specific interactions
Authors: Huntley Miriam H. , Murugan Arvind , Brenner Michael P.
Published: May 2016

Significance

The past 15 years have seen a proliferation of experimental techniques aimed at engineering self-assembled structures. These bottom–up techniques rely on specific interactions between components that arise from diverse physical mechanisms such as chemical affinities and shape complementarity attraction. Comparisons of specificity across such diverse systems, each with unique physics and constraints, can be difficult. Here we describe an information theoretic measure, capacity, to quantify specificity in a range of recent experimental systems. Capacity quantifies the maximal amount of information that can be encoded and then resolved by a system of specific interactions, as a function of experimentally tunable parameters. Our framework can be applied to specific interactions of diverse origins, from colloidal experiments to protein interactions.
Meaningful call combinations and compositional processing in the southern pied babbler
Authors: Engesser Sabrina , Ridley Amanda R. , Townsend Simon W.
Published: May 2016

Significance

Human language is syntactic in its nature: meaningful words are assembled into larger meaningful phrases or sentences. How unique this ability is to humans remains surprisingly unclear. A considerable body of work has indicated that birds are capable of combining sounds into large, elaborate songs, but there is currently no evidence suggesting that these structures are syntactic. Here, we provide important evidence for this ability in a highly social bird. Specifically, pied babblers combine two functionally distinct vocalizations into a larger sequence, the function of which is related to the function of its parts. Our work adds important evidence to the variation and distribution of combinatorial vocal mechanisms outside humans and provides insights into potentially early forms of human syntactic communication.
Elucidation of tonic and activated B-cell receptor signaling in Burkitt’s lymphoma provides insights into regulation of cell survival
Authors: Corso Jasmin , Pan Kuan-Ting , Walter Roland , Doebele Carmen , Mohr Sebastian , Bohnenberger Hanibal , Ströbel Philipp , Lenz Christof , Slabicki Mikolaj , Hüllein Jennifer , Comoglio Federico , Rieger Michael A. , Zenz Thorsten , Wienands Jürgen , Engelke Michael , Serve Hubert , Urlaub Henning , Oellerich Thomas
Published: May 2016

Significance

B-cell receptor (BCR) signaling promotes the survival of malignant B cells, such as Burkitt’s lymphoma (BL) and the activated B-cell–like subtype of diffuse large B-cell lymphoma (ABC-DLBCL). In contrast to ABC-DLBCL, which depends on chronic activation of the BCR, BL cells rely on tonic BCR signaling that is antigen-independent. Elucidation and systematic comparison of tonic and activated BCR signaling led to the identification of novel signaling effectors, including ACTN4 and ARFGEF2, which were identified as regulators of BL-cell survival. Beyond its relevance to the understanding of BL pathogenesis and the development of targeted therapies, our study complements the general understanding of BCR-induced processes also in physiological settings.
Syntax compensates for poor binding sites to encode tissue specificity of developmental enhancers
Authors: Farley Emma K. , Olson Katrina M. , Zhang Wei , Rokhsar Daniel S. , Levine Michael S.
Published: May 2016

Significance

Transcriptional enhancers are elements within the genome that control when and where genes are expressed. Although they were identified more than 3 decades ago, how DNA sequence encodes enhancer function remains unclear. Here we show that enhancer syntax (the order, orientation, and spacing of transcription factor binding sites) is important for tissue-specific gene expression. Surprisingly, enhancers with low-affinity binding sites can mediate robust tissue specific patterns of gene expression when they are organized with optimal syntax. Such enhancers may be a vastly underappreciated feature of the regulatory genome.
Clonal integration facilitates the colonization of drought environments by plant invaders
Authors: Lechuga-Lago Yaiza , Sixto-Ruiz Marta , Roiloa Sergio R. , González Luís
Published: May 2016

Biological invasion represents one of the main threats for biodiversity conservation at the global scale. Identifying the mechanisms underlying the process of biological invasions is a crucial objective in the prediction of scenarios of future invasions and the mitigation of their impacts. In this sense, some plant attributes might better explain the success of invasive plant species than others. Recently, clonal growth has been identified as an attribute that could contribute to the invasiveness of plants. In this experiment, we aim to determine the effect of physiological integration (one of the most striking attributes associated with clonal growth) in the performance (at morphological and physiological levels) of the aggressive invader Carpobrotus edulis , when occupying stressful environments. To achieve this objective we performed a greenhouse experiment in which apical ramets of C. edulis were water-stressed and the connection with the basal ramets was either left intact (physiological integration is allowed) or severed (physiological integration is impeded). Our results show that clonal integration allowed apical ramets to buffer drought stress in terms of photochemical activity, and as a consequence, to increase their growth in comparison with severed apical ramets. Interestingly, this increase in biomass was mainly due to the production of aboveground structures, increasing the spread along the soil surface, and consequently having important implications for the colonization success of new environments by this aggressive invader.
Effectiveness of cuticular transpiration barriers in a desert plant at
controlling water loss at high temperatures
Authors: Schuster Ann-Christin , Burghardt Markus , Alfarhan Ahmed , Bueno Amauri , Hedrich Rainer , Leide Jana , Thomas Jacob , Riederer Markus
Published: May 2016

Maintaining the integrity of the cuticular transpiration barrier even at elevated temperatures is of vital importance especially for hot-desert plants. Currently, the temperature dependence of the leaf cuticular water permeability and its relationship with the chemistry of the cuticles are not known for a single desert plant. This study investigates whether (i) the cuticular permeability of a desert plant is lower than that of species from non-desert habitats, (ii) the temperature-dependent increase of permeability is less pronounced than in those species and (iii) whether the susceptibility of the cuticular permeability barrier to high temperatures is related to the amounts or properties of the cutin or the cuticular waxes. We test these questions with Rhazya stricta using the minimum leaf water vapour conductance ( g  min ) as a proxy for cuticular water permeability. g  min of R. stricta (5.41 × 10 −5 m s −1 at 25 °C) is in the upper range of all existing data for woody species from various non-desert habitats. At the same time, in R. stricta , the effect of temperature (15–50 °C) on g  min (2.4-fold) is lower than in all other species (up to 12-fold). Rhazya stricta is also special since the temperature dependence of g  min does not become steeper above a certain transition temperature. For identifying the chemical and physical foundation of this phenomenon, the amounts and the compositions of cuticular waxes and cutin were determined. The leaf cuticular wax (251.4 μg cm −2 ) is mainly composed of pentacyclic triterpenoids (85.2% of total wax) while long-chain aliphatics contribute only 3.4%. In comparison with many other species, the triterpenoid-to-cutin ratio of R. stricta (0.63) is high. We propose that the triterpenoids deposited within the cutin matrix restrict the thermal expansion of the polymer and, thus, prevent thermal damage to the highly ordered aliphatic wax barrier even at high temperatures.
Computational approach to dendritic spine taxonomy and shape transition analysis
Authors: Kusmierczyk Tomasz , Lukasik Michal , Magnowska Marta , Roszkowska Matylda , Bokota Grzegorz , Plewczynski Dariusz
Published: May 2016

The common approach in morphological analysis of dendritic spines is to categorize spines into subpopulations based on whether they are stubby, mushroom, thin, or filopodia. Corresponding cellular models of synaptic plasticity, long-term potentiation, and long-term depression associate synaptic strength with either spine enlargement or spine shrinkage. Although a variety of automatic spine segmentation and feature extraction methods were developed recently, no approaches allowing for an automatic and unbiased distinction between dendritic spine subpopulations and detailed computational models of spine behavior exist.

We propose an automatic and statistically based method for the unsupervised construction of spine shape taxonomy based on arbitrary features. The taxonomy is then utilized in the newly introduced computational model of behavior, which relies on transitions between shapes. Models of different populations are compared using supplied bootstrap-based statistical tests.

We compared two populations of spines at two time points. The first population was stimulated with long-term potentiation, and the other in the resting state was used as a control. The comparison of shape transition characteristics allowed us to identify differences between population behaviors. Although some extreme changes were observed in the stimulated population, statistically significant differences were found only when whole models were compared. Therefore, we hypothesize that the learning process is related to the subtle changes in the whole ensemble of different dendritic spine structures, but not at the level of single shape classes.

The source code of our software is freely available for non-commercial use1.
Data-Driven Phenotypic Categorization for Neurobiological Analyses: Beyond DSM-5 Labels
Authors: Van Dam Nicholas T. , O’Connor David , Marcelle Enitan T. , Ho Erica J. , Craddock R. Cameron , Tobe Russell H. , Gabbay Vilma , Hudziak James J. , Castellanos F. Xavier , Leventhal Bennett L. , Milham Michael P.
Published: May 2016

Background

Data-driven approaches can capture behavioral and biological variation currently unaccounted for by contemporary diagnostic categories, thereby enhancing the ability of neurobiological studies to characterize brain-behavior relationships.

Methods

A community-ascertained sample of individuals (N=347, ages 18–59) completed a battery of behavioral measures, psychiatric assessment, and resting state functional magnetic resonance imaging (R-fMRI) in a cross-sectional design. Bootstrap-based exploratory factor analysis was applied to 49 phenotypic subscales from 10 measures. Hybrid Hierarchical Clustering was applied to resultant factor scores to identify nested groups. Adjacent groups were compared via independent samples t-tests and chi-square tests of factor scores, syndrome scores, and psychiatric prevalence. Multivariate Distance Matrix Regression examined functional connectome differences between adjacent groups.

Results

Reduction yielded six factors, which explained 77.8% and 65.4% of the variance in exploratory and constrained exploratory models, respectively. Hybrid Hierarchical Clustering of these 6 factors identified 2, 4, and 8 nested groups (i.e., phenotypic communities). At the highest clustering level, the algorithm differentiated functionally adaptive and maladaptive groups. At the middle clustering level, groups were separated by problem type (maladaptive groups; internalizing vs. externalizing problems) and behavioral type (adaptive groups; sensation-seeking vs. extraverted/emotionally stable). Unique phenotypic profiles were also evident at the lowest clustering level. Group comparisons exhibited significant differences in intrinsic functional connectivity at the highest clustering level in somatomotor, thalamic, basal ganglia, and limbic networks.

Conclusions

Data-driven approaches for identifying homogenous subgroups, spanning typical function to dysfunction not only yielded clinically meaningful groups, but captured behavioral and neurobiological variation among healthy individuals as well.
Refined biomimetic model of chronic pain is healed with erythropoietin
Authors: Hannaman Mary R. , Fitts Douglas A. , Doss Rose M. , Weinstein David E. , Bryant Joseph L.
Published: May 2016

Humans suffering with chronic pain may have no evidence of a lesion or disease. They are managed with a morass of drugs and invasive procedures. In many, their persistent pain occurs after the healing of a soft tissue injury, with a neural source hypothesized. Opiates, commonly used to mitigate their symptoms, can cause an increase in neuropathic pain over time. Current animal models of neuropathic pain commonly create direct neural damage with open surgeries using ligatures, neurectomies, chemicals or other forms of intentional trauma. However, we have observed clinically that after an injury in humans, the naturally occurring process of tissue repair can cause chronic neural pain. We show here how the refined biomimetic NeuroDigm GELTM Model, in the mature male rat, gradually induces neuropathic pain behavior with a nonsurgical percutaneous injection of tissue-derived hydrogel in the tunnel of the distal tibial nerve. This perineural model creates a mononeuritis with the biogenic matrix induction of tissue remodeling, the last stage of tissue repair. Repeated behavioral analgesic testing over 5 months in the model implied a unique predictive validity for all analgesics tested. Morphine, initially effective, had an increase in pain behavior over time, suggesting an opioid-induced hyperalgesia, as seen in humans. Celecoxib produced no analgesia, while gabapentin and duloxetine at low doses had profound analgesia. Histology reveals focal neural remodeling, with neural regeneration, as in human biopsies. For the first time, targeted erythropoietin appears to heal neural pain, by extinguishing bilateral pain behavior present for over 4 months.

translational model, neuropathic pain, erythropoietin, neural regeneration, soft tissue injuries, neuritis, tissue repair, hydrogel, animal model of disease, neural remodeling, age, opioid-induced hyperalgesia, morphine resistance, analgesics, refined pain model, matrix remodeling, neuroinflammation, predictive validity, habituation, estrogen
GeMSTONE: Orchestrated Prioritization of Human Germline Mutations in the Cloud
Authors: Chen Siwei , Beltrán Juan Felipe , Wei Xiaomu , Lipkin Steven , Esteban-Jurado Clara , Franch-Expósito Sebastià , Castellví-Bel Sergi , Yu Haiyuan
Published: May 2016

Integrative analysis of whole-genome/exome-sequencing data has been challenging, especially for the non-programming research community, as it requires leveraging an inordinate number of computational tools. Even computational biologists find it unexpectedly difficult to reproduce results from others or optimize their own strategies in an end-to-end workflow. We introduce Germline Mutation Scoring Tool fOr Next-generation sEquencing data (GeMSTONE), a cloud- based variant prioritization tool with high-level customization and a comprehensive collection of bioinformatics tools and data libraries (http://gemstone.yulab.org/). GeMSTONE generates and readily accepts a sharable 'recipe' file for each run to either replicate existing results or analyze new data with identical parameters.
Simple settlement decisions explain common dispersal patterns in territorial species
Authors: Gilroy James J. , Lockwood Julie L.
Published: May 2016

Dispersal is one of the least‐understood aspects of animal behaviour. For example, little is known of the mechanisms that determine how individuals express different dispersal behaviours in response to different circumstances. Uncovering these mechanisms is important for our understanding of spatial population dynamics.

Using agent‐based simulations, we examine how simple decision rules generate individual‐level dispersal plasticity, and how this can influence population‐scale dispersal dynamics. We model a territorial, monogamous population inhabiting a completely homogeneous environment. Dispersal variability therefore emerges solely as a result of between‐individual interactions (competition, settlement, reproduction), which are governed by simple decision‐making algorithms.

We show that complex dispersal dynamics, including sex biases and strong density dependence, emerge naturally from simple rule‐based behaviours. Dispersal is particularly sensitive to the inclusion of mate availability as a criterion for settlement: if neither sex evaluates mate availability, dispersal distances tend to decline at low densities, leading to a strong Allee effect from reduced pairing success. If one sex evaluates mate availability (females), Allee effects are largely avoided, but female‐biased dispersal generates increasingly male‐biased adult sex ratios at low densities. Sex biases are eliminated if both sexes evaluate mate availability, but population growth rates tend to be reduced due to survival costs and reduced pairing success.

Our models suggest that simple decision mechanisms can explain several dynamic patterns that are commonly observed among territorial species. Importantly, these patterns emerge in the absence of environmental heterogeneity or between‐individual variation in dispersal phenotypes, two conditions that are often invoked to explain dispersal heterogeneity in nature. This has implications for studies seeking to examine the causes of dispersal variability in wild populations, suggesting that observed patterns could be largely driven by the social and demographic conditions experienced by sampled individuals.

Further insights could be gained by examining how selection operates on decision rules in different life‐history and environmental circumstances, and how this might interact with selection on other demographic traits. Uncovering the decision rules used during settlement should be a priority for those wishing to understand and predict dispersal patterns in nature.
Trade‐offs and mixed infections in an obligate‐killing insect pathogen
Authors: Redman Elizabeth M. , Wilson Kenneth , Cory Jenny S.
Published: May 2016

Natural populations of pathogens are frequently composed of numerous interacting strains. Understanding what maintains this diversity remains a key focus of research in disease ecology. In addition, within‐host pathogen dynamics can have a strong impact on both infection outcome and the evolution of pathogen virulence, and thus, understanding the impact of pathogen diversity is important for disease management.

We compared eight genetically distinguishable variants from Spodoptera exempta nucleopolyhedrovirus (SpexNPV) isolated from the African armyworm, Spodoptera exempta. NPVs are obligate killers, and the vast majority of transmission stages are not released until after the host has died.

The NPV variants differed significantly in their virulence and could be clustered into two groups based on their dose–response curves. They also differed in their speed of kill and productivity (transmission potential) for S. exempta. The mixed‐genotype wild‐type (WT) SpexNPV, from which each variant was isolated, was significantly more virulent than any individual variant and its mean mortality rate was within the fastest group of individual variants. However, the WT virus produced fewer new infectious stages than any single variant, which might reflect competition among the variants.

A survival analysis, combining the mortality and speed of kill data, confirmed the superiority of the genetically mixed WT virus over any single variant. Spodoptera exempta larvae infected with WT SpexNPV were predicted to die 2·7 and 1·9 times faster than insects infected with isolates from either of the two clusters of genotypes.

Theory suggests that there are likely to be trade‐offs between pathogen fitness traits. Across all larvae, there was a negative linear relationship between virus yield and speed of kill, such that more rapid host death carried the cost of producing fewer transmission stages. We also found a near‐significant relationship for the same trend at the intervariant level. However, there was no evidence for a significant relationship between the induced level of mortality and transmission potential (virus yield) or speed of kill.
Secretion of small proteins is species‐specific withinAspergillussp
Authors: Valette Nicolas , Benoit‐Gelber Isabelle , Falco Marcos Di , Wiebenga Ad , de Vries Ronald P. , Gelhaye Eric , Morel‐Rouhier Mélanie
Published: May 2016

Small secreted proteins (SSP) have been defined as proteins containing a signal peptide and a sequence of less than 300 amino acids. In this analysis, we have compared the secretion pattern ofSSPs among eight aspergilli species in the context of plant biomass degradation and have highlighted putative interesting candidates that could be involved in the degradative process or in the strategies developed by fungi to resist the associated stress that could be due to the toxicity of some aromatic compounds or reactive oxygen species released during degradation. Among these candidates, for example, some stress‐related superoxide dismutases or some hydrophobic surface binding proteins (HsbA) are specifically secreted according to the species . Since these latter proteins are able to recruit lytic enzymes to the surface of hydrophobic solid materials and promote their degradation, a synergistic action of HsbA with the degradative system may be considered and need further investigations. TheseSSPs could have great applications in biotechnology by optimizing the efficiency of the enzymatic systems for biomass degradation.
The USGS Water Availability and Use Science Program: Needs, Establishment, and Goals of a Water Census
Authors: Michelsen Ari M. , Jones Sonya , Evenson Eric , Blodgett David
Published: May 2016

Many reports have recognized the need for a national water census for the United States and have called upon the U.S. Geological Survey to undertake this challenge. For example, the National Science and Technology Council stated: “The United States has a strong need for an ongoing census of water that describes the status of our Nation's water resource at any point in time and identifies trends over time.” Responding to the need for this information, the U.S. Congress established the SECURE Water Act. The directives are to provide a more accurate assessment of the status of the water resources of the United States; determine the quantity of water available for beneficial uses; identify long‐term trends in water availability; assist in determination of the quality of the water resources; and develop the basis for an improved ability to forecast the availability of water for future economic, energy production, and environmental uses. This article provides summary and new information on the process and progress on work to estimate water budget components nationwide, involvement of stakeholder interests, efforts to examine water‐use characteristics throughout the Nation, studies of water availability in geographically focused areas and the initiation of methods to provide open access to existing and new water resources information contributing to Open Water Data Initiative (OWDI) efforts and objectives.
Transfer Pricing: Strategies, Practices, and Tax Minimization
Authors: Klassen Kenneth J. , Lisowsky Petro , Mescall Devan
Published: May 2016

Using a survey of tax executives from multinational corporations, we document that some firms set their transfer pricing strategy to minimize tax payments, but more firms focus on tax compliance. We estimate that a firm focusing on minimizing taxes has a GAAP effective tax rate that is 6.6 percentage points lower and generates about $43 million more in tax savings, on average, than a firm focusing on tax compliance. Available COMPUSTAT data on sample firms confirm our survey‐based inferences. We also find that transfer pricing‐related tax savings are greater when higher foreign income, tax haven use, and R&D activities are combined with a tax minimization strategy. Finally, compliance‐focused firms report lower FIN 48 tax reserves than tax‐minimizing firms, consistent with the former group using less uncertain transfer pricing arrangements. Collectively, our study provides direct evidence that multinational firms have differing internal priorities for transfer pricing, and that these differences are strongly related to the taxes reported by these firms.
Sex and the Lab: An Alcohol‐Focused Commentary on the NIH Initiative to Balance Sex in Cell and Animal Studies
Authors: Guizzetti Marina , Davies Daryl L. , Egli Mark , Finn Deborah A. , Molina Patricia , Regunathan Soundar , Robinson Donita L. , Sohrabji Farida
Published: May 2016

In May 2014, Dr. Francis Collins, the director of U.S. National Institutes of Health (NIH), and Dr. Janine Clayton, the director of the U.S. National Institutes of Health Office of Research on Women's Health, published a commentary in the journal Nature announcing new policies to ensure that preclinical research funded by the NIH considers both males and females. While these policies are still developing, they have already generated great interest by the scientific community and triggered both criticism and applause. This review provides a description and interpretation of the NIH guidelines, and it traces the history that led to their implementation. As expected, this NIH initiative generated some anxiety in the scientific community. The use of female animals in the investigation of basic mechanisms is perceived to increase variability in the results, and the use of both sexes has been claimed to slow the pace of scientific discoveries and to increase the cost at a time characterized by declining research support. This review discusses issues related to the study of sex as a biological variable (SABV) in alcohol studies and provides examples of how researchers have successfully addressed some of them. A practical strategy is provided to include both sexes in biomedical research while maintaining control of the research direction. The inclusion of sex as an important biological variable in experimental design, analysis, and reporting of preclinical alcohol research is likely to lead to a better understanding of alcohol pharmacology and the development of alcohol use disorder, may promote drug discovery for new pharmacotherapies by increasing scientific rigor, and may provide clinical benefit to women's health. This review aims to promote the understanding of the NIH's SABV guidelines and to provide alcohol researchers with a theoretical and practical framework for working with both sexes in preclinical research.
The health of older Aboriginal and Torres Strait Islander peoples
Authors: LoGiudice Dina
Published: May 2016

The health of Aboriginal Australians is poorer than that of all other Indigenous cultures in developed nations, and recent studies suggest high rates of dementia and other conditions that are common in old age. This has implications for health promotion, provision of services and planning for older age in these communities. This article provides an overview on the health of Older Aboriginal Australians.
Spatial and temporal patterns of home range use by olive baboons (Papio anubis) in eastern Laikipia, Kenya
Authors: Musyoki Charles M. , Strum Shirley C.
Published: May 2016

The study investigated the relationship between topography, seasonal food availability and home range use by a troop of olive baboons (Papio anubis) in a dry savannah environment. Valleys were the most utilized parts of the home range in dry seasons while old boma sites were more frequently used in the wet season. Herb‐layer food biomass decreased significantly in dry seasons. The flowers of both Acacia tortilis and Acacia etbaica were available only in dry seasons with valleys having the highest biomass. The biomass of Acacia nilotica seeds was higher in valleys than on other locations. Leaves of the shrub Lycium europaeum were available on all locations in the wet season but valleys had the highest biomass of this food type. Herb‐layer baboon food biomass at ridge tops, slopes, valleys and old boma sites showed similar trends in productivity between seasons. Baboons tracked food along the soil catenas by feeding at ridge tops and old boma sites where foods were available during the wet season and exploiting food sources at the valleys during the dry seasons. Food availability was related to the catena effect and baboons used the catenas in the home range in a predictable manner.
Trial of labor after myomectomy and uterine rupture: a systematic review
Authors: Gambacorti‐Passerini Zita , Gimovsky Alexis C. , Locatelli Anna , Berghella Vincenzo
Published: May 2016

Introduction

There is concern about the risk of uterine rupture in the subsequent pregnancy after myomectomy. This risk is reported in literature to be around 0.7–1%. The aim of this study was to evaluate the incidence of uterine rupture and associated risk factors in women who had a trial of labor after prior myomectomy.

Material and methods

A systematic review of the literature was performed including all cohort studies with at least five cases reporting outcomes of pregnancies after prior myomectomy. The terms “myomectomy”, “pregnancy”, “trial of labor” and “uterine rupture” were used in PubMed and EMBASE searches for identification purposes. Every reference was reviewed for possible inclusion and all eligible cases of uterine rupture were considered.

Results

Twenty‐three studies with at least five cases of pregnancy after myomectomy were identified, with an overall incidence of uterine rupture of 0.6% (0.3–1.1%) (n = 11/1825). Of these 23 studies, 11 studies reported detailed data about trial of labor after myomectomy and related pregnancy outcomes, including 1034 pregnancies and 756 viable (≥24 weeks) deliveries. The overall incidence of uterine rupture after myomectomy in the included studies was 0.93% (0.45–1.92%) (n = 7/756); specifically, it was 0.47% (0.13–1.70%) (n = 2/426) in women undergoing trial of labor after myomectomy, and 1.52% (0.65–3.51%) (n = 5/330) in women before the onset of labor. Of the seven uterine ruptures, five (71%) occurred within 36 weeks (range 24–40 weeks).

Conclusions

Trial of labor after myomectomy is associated with a 0.47% risk of uterine rupture. There were no identified risk factors among the variables studied. The present systematic review of the literature revealed that uterine rupture after prior myomectomy occurred mainly before 36 weeks and before labor.
Placental Growth Factor Triggers Epithelial‐to‐Mesenchymal Transition‐like Changes in Rat Type II Alveolar Epithelial Cells: Activation of Nuclear Factor κB Signalling Pathway
Authors: Zhang Liang , Zhao Shuang , Yuan Lijie , Wu Hongmin , Jiang Hong , Luo Gang
Published: May 2016

Epithelial‐to‐mesenchymal transition (EMT) occurs frequently in lung epithelium in response to damage stimuli, such as inflammation and oxidative stress. Our group has already found an excessive release of placental growth factor (PLGF) in hyperoxic lung injury in newborn rodents. Nonetheless, whether this increased PLGF plays a role in mediating EMT process of alveolar epithelial cells (AECs) is unclear and requires further investigation. In this study, primary type II AECs were first isolated for neonatal Sprague Dawley (SD) rats and treated with different doses (25 or 100 ng/ml) of recombinant PLGF for 48 hr. As compared to the untreated AECs, exogenous PLGF induced a reduction in E‐cadherin (a critical epithelial maker) and increases in vimentin and fibronectin (mesenchymal markers) in a dose‐dependent manner. The higher dose was more potent in promoting the EMT‐like changes in AECs. We also found that PLGF promoted the degradation of nuclear factor κB (NFκB) inhibitor (IκBα), induced phosphorylation of NFκB p65 at Ser 536 and enhanced p65 nuclear translocation in primary AECs. In addition, the NFκB inhibitor BAY 11‐7082 partly counteracted PLGF‐induced alterations in EMT‐related proteins in rat AECs. In summary, our study demonstrates that exogenous PLGF can induce EMT‐like changes in type II AECs at least partly by activating NFκB signalling transduction in vitro. PLGF may play a role in driving fibrotic lesions and thus can be a promising target for lung diseases.
Interactive print: The design of cognitive tasks in blended augmented reality and print documents
Authors: Nadolny Larysa
Published: May 2016

The combination of print materials and augmented reality in education is increasingly accessible due to advances in mobile technologies. Using familiar paper‐based activities overlaid with digital items, also known as interactive print, educators can create a custom learning experience for students. There is very little guidance on the design of interactive print activities, particularly methods used to structure the appropriate levels of cognitive load for engagement with content. This study examined over 13 000 data points in two different interactive print activities for trends and patterns in user engagement. The results showed that the instructional design, number of digital interactions and pedagogical strategies influenced user interactions within the activity. In particular, a page designed with immersion, instant feedback, a focused task and high level cognitive tasks engaged users to interact with the digital content.
Influences of an inquiry‐based ubiquitous gaming design on students’ learning achievements, motivation, behavioral patterns, and tendency towards critical thinking and problem solving
Authors: Hwang Gwo‐Jen , Chen Chih‐Hung
Published: May 2016

In this paper, an inquiry‐based ubiquitous gaming approach was proposed. The objective of the study was to enhance students’ performances in in‐field learning activities. To show the advantages of the approach, an experiment was carried out to assess the effects of it on students’ learning achievement, motivation, critical thinking, and problem solving. Furthermore, the students’ behavioral patterns were investigated via content and sequential analysis methods. The experimental outcomes show that the approach promoted students’ performances of learning achievement and intrinsic motivation; moreover, the students’ perceptions of their problem solving and critical thinking were significantly promoted as well. The learning behavior analysis further show that the designated approach stimulated the participants to actively engage in field observation, comparison, and data searching in the context ware in‐field learning activity.
Magnetic resonance microscopy may enable distinction between normal histomorphological features and prostate cancer in the resected prostate gland
Authors: Durand Matthieu , Jain Manu , Robinson Brian , Aronowitz Eric , El Douahy Youssef , Leung Robert , Scherr Douglas S. , Ng Amelia , Donzeau Dominique , Amiel Jean , Spincemaille Pascal , Villers Arnauld , Ballon Douglas J.
Published: May 2016

Objectives

To determine imaging protocol parameters for characterization of prostate tissue at histological length scales.

Material and Methods

Rapid acquisition with relaxation enhancement, spin echo and gradient echo fast low angle shot data were acquired using ex vivo 3‐Tesla or 7‐Tesla magnetic field strengths from fresh prostatectomy specimens (n = 15) obtained from either organ donor or patients with prostate cancer (PCa). To achieve the closest correspondence between histopathological components and magnetic resonance imaging (MRI) results, in terms of resolution and sectioning planes, multiple high‐resolution imaging protocols (ranging from a few minutes to overnight) were tested. Ductograms were generated as part of image post‐processing. Specimens were subsequently submitted for histopathological evaluation.

Results

A total of seven imaging protocols were tested. Ex vivo 7‐Tesla MRI identified normal components of prostate glands, including ducts, blood vessels, concretions and stroma at a spatial resolution of 60 × 60 × 60 μm3 to 107 × 107 × 500 μm3. Malignant glands and nests of tumour cells identified at 60 × 60 × 90 μm3 were highly similar to low‐magnification (×2) histopathology. Ductograms enhanced the differentiation between benign and malignant glands. The results of the present study were encouraging, and further work is warranted with a larger sample size.

Conclusion

We showed that critical histopathological features of the prostate gland can be identified with high‐resolution ex vivo MRI examination and this offers promise that MRI microscopy of PCa will ultimately be possible in vivo.
A phenology of the evolution of endothermy in birds and mammals
Authors: Lovegrove Barry G.
Published: May 2016

Recent palaeontological data and novel physiological hypotheses now allow a timescaled reconstruction of the evolution of endothermy in birds and mammals. A three‐phase iterative model describing how endothermy evolved from Permian ectothermic ancestors is presented. In Phase One I propose that the elevation of endothermy – increased metabolism and body temperature (Tb) – complemented large‐body‐size homeothermy during the Permian and Triassic in response to the fitness benefits of enhanced embryo development (parental care) and the activity demands of conquering dry land. I propose that Phase Two commenced in the Late Triassic and Jurassic and was marked by extreme body‐size miniaturization, the evolution of enhanced body insulation (fur and feathers), increased brain size, thermoregulatory control, and increased ecomorphological diversity. I suggest that Phase Three occurred during the Cretaceous and Cenozoic and involved endothermic pulses associated with the evolution of muscle‐powered flapping flight in birds, terrestrial cursoriality in mammals, and climate adaptation in response to Late Cenozoic cooling in both birds and mammals. Although the triphasic model argues for an iterative evolution of endothermy in pulses throughout the Mesozoic and Cenozoic, it is also argued that endothermy was potentially abandoned at any time that a bird or mammal did not rely upon its thermal benefits for parental care or breeding success. The abandonment would have taken the form of either hibernation or daily torpor as observed in extant endotherms. Thus torpor and hibernation are argued to be as ancient as the origins of endothermy itself, a plesiomorphic characteristic observed today in many small birds and mammals.
The neutrophil‐to‐lymphocyte ratio predicts major perioperative complications in patients undergoing colorectal surgery
Authors: Josse J. M. , Cleghorn M. C. , Ramji K. M. , Jiang H. , Elnahas A. , Jackson T. D. , Okrainec A. , Quereshy F. A.
Published: May 2016

Aim

The objective of the study was to evaluate the association between the neutrophil‐to‐lymphocyte ratio (NLR) and the occurrence of perioperative complications in patients undergoing colorectal surgery.

Method

A retrospective cohort study was conducted of patients who underwent resection for suspected or confirmed colorectal cancer from 2004 to 2012. Patient cohorts with a high vs low NLR were defined by receiver operating characteristic curve analysis. Univariate and multivariate logistic regression was used to determine whether patients with elevated NLR were more likely to suffer perioperative complications.

Results

In all, 583 patients were included. A preoperative NLR greater than or equal to 2.3 was significantly associated with a major perioperative complication (OR 2.52, 95% CI 1.26–5.01). On multivariate analysis, a high NLR (OR 2.25, 95% CI 1.12–4.52) and Charlson Comorbidity Index ≥ 3 (OR 4.55, 95% CI 2.17–9.56) were significantly related to major morbidity. No relationships were found between an elevated preoperative NLR and complication type, although there was a trend towards the occurrence of anastomotic leakage.

Conclusion

Preoperative NLR ≥ 2.3 may be a risk factor for major surgical complications following colorectal resection. Further study is needed to validate this threshold and evaluate the clinical implications of these findings.
Robotic versus conventional laparoscopic rectal cancer surgery in obese patients
Authors: Gorgun E. , Ozben V. , Costedio M. , Stocchi L. , Kalady M. , Remzi F.
Published: May 2016

Aim

Obesity adds to the technical difficulty of laparoscopic colorectal surgery. The robotic approach has the potential to overcome this limitation because of its proposed technical advantages over laparoscopy. The aim of this retrospective study was to compare the short‐term outcomes of robotic surgery (RS) vs conventional laparoscopy surgery (LS) in this patient population.

Method

Patients with a body mass index ≥ 30 kg/m2 undergoing RS or LS for rectal cancer between January 2011 and June 2014 were identified from an institutional database. Perioperative parameters, oncological findings and postoperative 30‐day short‐term outcomes were compared between the RS and LS groups.

Results

The RS and LS groups included 29 and 27 patients, respectively. Groups were comparable in terms of patient demographics, body mass index (34.9 ± 7.2 vs 35.2 ± 5.0 kg/m2, P = 0.71), comorbidities, surgical and tumour characteristics. Comparison of the intra‐operative findings revealed no significant differences between the groups including operative time (329.0 ± 102.2 vs 294.6 ± 81.1 min, P = 0.13), blood loss (434.0 ± 612.4 vs 339.4 ± 271.9 ml, P = 0.68), resection margin involvement (6.9% vs 7.4%, P = 0.99), conversions (3.4% vs 18.5%, P = 0.09) and complications (6.9% vs 0%, P = 0.49). Regarding postoperative outcomes, there were no significant differences in morbidity except that robotic surgery was associated with a quicker return of bowel function (median 3 vs 4 days, P = 0.01) and shorter hospital stay (median 6 vs 7 days, P = 0.02).

Conclusion

Robotic surgery for rectal cancer in obese patients has short‐term outcomes similar to laparoscopy, but accelerated postoperative recovery.
Epileptic networks are strongly connected with and without the effects of interictal discharges
Authors: Iannotti Giannina R. , Grouiller Frédéric , Centeno Maria , Carmichael David W. , Abela Eugenio , Wiest Roland , Korff Christian , Seeck Margitta , Michel Christoph , Pittau Francesca , Vulliemoz Serge
Published: May 2016

Objective

Epilepsy is increasingly considered as the dysfunction of a pathologic neuronal network (epileptic network) rather than a single focal source. We aimed to assess the interactions between the regions that comprise the epileptic network and to investigate their dependence on the occurrence of interictal epileptiform discharges (IEDs).

Methods

We analyzed resting state simultaneous electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) recordings in 10 patients with drug‐resistant focal epilepsy with multifocal IED‐related blood oxygen level–dependent (BOLD) responses and a maximum t‐value in the IED field. We computed functional connectivity (FC) maps of the epileptic network using two types of seed: (1) a 10‐mm diameter sphere centered in the global maximum of IED‐related BOLD map, and (2) the independent component with highest correlation to the IED‐related BOLD map, named epileptic component. For both approaches, we compared FC maps before and after regressing out the effect of IEDs in terms of maximum and mean t‐values and percentage of map overlap.

Results

Maximum and mean FC maps t‐values were significantly lower after regressing out IEDs at the group level (p < 0.01). Overlap extent was 85% ± 12% and 87% ± 12% when the seed was the 10‐mm diameter sphere and the epileptic component, respectively.

Significance

Regions involved in a specific epileptic network show coherent BOLD fluctuations independent of scalp EEG IEDs. FC topography and strength is largely preserved by removing the IED effect. This could represent a signature of a sustained pathologic network with contribution from epileptic activity invisible to the scalp EEG.