bluuebunny/crossref_metadata_2025 huggingface dataset:
The potential of utrophin and dystrophin combination therapies for Duchenne muscular dystrophy
Authors: Guiraud Simon , Edwards Benjamin , Babbs Arran , Squire Sarah E , Berg Adam , Moir Lee , Wood Matthew J , Davies Kay E
Published: March 2019

Duchenne muscular dystrophy (DMD) is a lethal neuromuscular disorder caused by loss of dystrophin. Several therapeutic modalities are currently in clinical trials but none will achieve maximum functional rescue and full disease correction. Therefore, we explored the potential of combining the benefits of dystrophin with increases of utrophin, an autosomal paralogue of dystrophin. Utrophin and dystrophin can be co-expressed and co-localized at the same muscle membrane. Wild-type (wt) levels of dystrophin are not significantly affected by a moderate increase of utrophin whereas higher levels of utrophin reduce wt dystrophin, suggesting a finite number of actin binding sites at the sarcolemma. Thus, utrophin upregulation strategies may be applied to the more mildly affected Becker patients with lower dystrophin levels. Whereas increased dystrophin in wt animals does not offer functional improvement, overexpression of utrophin in wt mice results in a significant supra-functional benefit over wt. These findings highlight an additive benefit of the combined therapy and potential new unique roles of utrophin. Finally, we show a 30% restoration of wt dystrophin levels, using exon-skipping, together with increased utrophin levels restores dystrophic muscle function to wt levels offering greater therapeutic benefit than either single approach alone. Thus, this combination therapy results in additive functional benefit and paves the way for potential future combinations of dystrophin- and utrophin-based strategies.
Preterm Birth and Maternal Mental Health: Longitudinal Trajectories and Predictors
Authors: Yaari Maya , Treyvaud Karli , Lee Katherine J , Doyle Lex W , Anderson Peter J
Published: March 2019

Objective

To examine trajectories of psychological distress in mothers of children born very preterm (VPT, <30 weeks gestation) and full term from 2 to 13 years after the birth, and examine predictors of maternal psychological distress over time within the VPT group.

Methods

Mothers of children born VPT (n = 159) and full term (n = 71) completed questionnaires assessing their psychological distress when their child was 2, 7, and 13 years of age. Mixed models were used to examine differences between groups in maternal psychological distress over time. Family social risk, child neonatal medial risk, child sex, multiple pregnancy, and child’s neurodevelopmental impairment in early childhood were examined as potential predictors of maternal psychological distress within the VPT group.

Results

Mothers of children born VPT displayed elevated psychological distress compared with mothers of full-term children, and this difference was consistent over time. Higher family social risk was associated with elevated maternal psychological distress throughout childhood across all time-points. There was evidence that mothers of children at higher neonatal medical risk displayed increasing psychological distress over time.

Conclusions

Mothers of children born VPT show prolonged psychological distress. Mothers from socially disadvantaged background and those whose child has neonatal medical complications may require extensive support to prevent prolonged psychological distress and promote optimal outcomes for children and families.
Ultra metal-poor stars: improved atmospheric parameters and NLTE abundances of magnesium and calcium
Authors: Sitnova T M , Mashonkina L I , Ezzeddine R , Frebel A
Published: March 2019

The most metal-poor stars are the oldest objects, they provide a unique opportunity to study the earliest epoch of the Galaxy formation and individual nucleosynthesis events. These stars should be investigated with a scrupulous care, taking into account all available photometric, spectroscopic, and astrometric informations. We determined atmospheric parameters for 17 ultra metal-poor (UMP) stars, using an extensive method based on colour-Teff calibrations, isochrones, Gaia DR2 trigonometric parallaxes, and non-local thermodynamic equilibrium (NLTE) analysis of the Ca i/Ca ii ionization equilibrium and the Balmer line wings. We updated the model atom of Ca i- ii by including recent quantum-mechanical rate coefficients for the Ca i + H i and Ca ii + H i inelastic collisions. For any line of Ca i and Ca ii in our sample stars, the changes in collisional data result in a shift of smaller than 0.05 dex in the NLTE abundance. We determined magnesium and calcium NLTE and LTE abundances of our sample stars. For 10 stars, we found close-to-solar [Ca/Mg] NLTE abundance ratios. In the remaining stars, magnesium and calcium abundances do not follow each other, such that [Ca/Mg] varies between −3.15 and + 0.36, suggesting a contribution to stellar Mg and Ca abundances from a small number of supernova explosions with different properties. The obtained atmospheric parameters will be used in the forthcoming paper to determine NLTE abundances of chemical elements observed in spectra of the UMP stars.
The gas fractions of dark matter haloes hosting simulated ∼L⋆ galaxies are governed by the feedback history of their black holes
Authors: Davies Jonathan J , Crain Robert A , McCarthy Ian G , Oppenheimer Benjamin D , Schaye Joop , Schaller Matthieu , McAlpine Stuart
Published: March 2019

We examine the origin of scatter in the relationship between the gas fraction and mass of dark matter haloes hosting present-day ∼L⋆ central galaxies in the EAGLE simulations. The scatter is uncorrelated with the accretion rate of the central galaxy’s black hole (BH), but correlates strongly and negatively with the BH’s mass, implicating differences in the expulsion of gas by active galactic nucleus feedback, throughout the assembly of the halo, as the main cause of scatter. Haloes whose central galaxies host undermassive BHs also tend to retain a higher gas fraction, and exhibit elevated star formation rates (SFRs). Diversity in the mass of central BHs stems primarily from diversity in the dark matter halo binding energy, as these quantities are strongly and positively correlated at fixed halo mass, such that ∼L⋆ galaxies hosted by haloes that are more (less) tightly bound develop central BHs that are more (less) massive than is typical for their halo mass. Variations in the halo gas fraction at fixed halo mass are reflected in both the soft X-ray luminosity and thermal Sunyaev–Zel’dovich flux, suggesting that the prediction of a strong coupling between the properties of galaxies and their halo gas fractions can be tested with measurements of these diagnostics for galaxies with diverse SFRs but similar halo masses.
Recessive Resistance Governed by a Major Quantitative Trait Locus Restricts Clover Yellow Vein Virus in Mechanically but Not Graft-Inoculated Cultivated Soybeans
Authors: Abe Junya , Wang Yongzhi , Yamada Tetsuya , Sato Masako , Ono Takuya , Atsumi Go , Abe Jun , Hajimorad M. R. , Nakahara Kenji S.
Published: March 2019

Clover yellow vein virus (ClYVV) infects and causes disease in legume plants. However, here, we found that ClYVV isolate No. 30 (ClYVV-No.30) inefficiently multiplied or spread via cell-to-cell movement in mechanically inoculated leaves of a dozen soybean (Glycine max) cultivars and resulted in failure to spread systemically. Soybean plants also had a similar resistance phenotype against additional ClYVV isolates. In contrast, all but one of 24 tested accessions of wild soybeans (G. soja) were susceptible to ClYVV-No.30. Graft inoculation of cultivated soybean TK780 with ClYVV-No.30–infected wild soybean B01167 scion resulted in systemic infection of the cultivated soybean rootstock. This suggests that, upon mechanical inoculation, the cultivated soybean inhibits ClYVV-No.30, at infection steps prior to the systemic spread of the virus, via vascular systems. Systemic infection of all F1 plants from crossing between TK780 and B01167 and of 68 of 76 F2 plants with ClYVV-No.30 indicated recessive inheritance of the resistance. Further genetic analysis using 64 recombinant inbred lines between TK780 and B01167 detected one major quantitative trait locus, designated d-cv, for the resistance that was positioned in the linkage group D1b (chromosome 2). The mapped region on soybean genome suggests that d-cv is not an allele of the known resistance genes against soybean mosaic virus.
Drought Exacerbates Botryosphaeria Dieback Symptoms in Grapevines and Confounds Host-based Molecular Markers of Infection byNeofusicoccum parvum
Authors: Galarneau Erin R. A. , Lawrence Daniel P. , Travadon Renaud , Baumgartner Kendra
Published: March 2019

Neofusicoccum parvum, causal fungus of the grapevine trunk disease Botryosphaeria dieback, attacks the wood of Vitis vinifera. Because lesions are internal, using putative host-based markers of infection from leaves for diagnosis is a nondestructive option. However, their specificity under drought stress is unknown. Potted ‘Cabernet-Sauvignon’ were inoculated with N. parvum in the greenhouse after wounding (IW), and with wounded and nonwounded noninoculated controls. At 2 weeks postinoculation (WPI), half of the plants were severely stressed (SS), receiving 30% water volume of the well-watered (WW) plants. Larger lesions at 12 WPI among IW-SS plants, compared with all other treatments, revealed an interactive effect of inoculation and drought on lesion length. Expression of eight putative marker genes was analyzed in leaves by qPCR at the onset of drought stress, and at 8 and 12 WPI. One marker showed consistent over-expression at 8 WPI in IW plants, regardless of water treatment, suggesting specificity to infection. By 12 WPI, higher expression of seven genes in all SS plants (across inoculation treatments) revealed specificity to drought. Cross-reactivity of markers to drought, therefore, limits their utility for disease diagnosis in the field, where drought induced by climate and deficit irrigation is common.
Anaerobic Soil Disinfestation to Manage Soilborne Diseases in Muck Soil Vegetable Production Systems
Authors: Testen Anna L. , Miller Sally A.
Published: March 2019

Anaerobic soil disinfestation (ASD) was evaluated as a tool for managing the root-knot nematode Meloidogyne hapla in lettuce (Lactuca sativa) and clubroot disease, caused by Plasmodiophora brassicae, in mustard greens (Brassica juncea) produced on Ohio muck soils in Huron and Stark Counties. In two consecutive years of field trials, wheat bran (20.2 Mg ha−1), molasses (10.1 Mg ha−1), and wheat bran (20.2 Mg ha−1) plus molasses (10.1 Mg ha−1) were assessed as ASD carbon sources and compared with nonamended controls. Data were collected from plants grown in the field and from plants grown in field-treated soils in growth chamber-based post-ASD bioassays. Anaerobic conditions developed in ASD-treated soils in both trial years, as indicated by polyvinyl chloride pipes painted with an iron oxide paint. Soil pH did not decrease during ASD at the Huron County site of the mustard greens clubroot trials in either trial year but soil pH decreased significantly during ASD in Stark County soils treated with ASD with either wheat bran or wheat bran plus molasses compared with control soils in both trial years. Impacts of ASD on plant biomass were inconsistent in direct field measurements; however, significantly higher biomasses were observed in lettuce and mustard greens grown in bioassay soils collected from plots treated with ASD with wheat bran-based amendments compared with plants grown in soils from control plots. Based on direct field measurements and bioassays, the use of ASD with any carbon source led to significant reductions in root-knot nematode galling on lettuce compared with controls. Reductions in clubroot severity in mustard greens following ASD were less consistent; however, significant reductions in clubroot severity were observed in the field in one trial year and in both years of bioassays. The results of these studies indicate that ASD is a promising tool for managing soilborne diseases in muck soil vegetable production systems.
Virulence of Puccinia triticina, the Wheat Leaf Rust Fungus, in the United States in 2017
Authors: Kolmer J. A
Published: March 2019

Samples of wheat leaves infected with the leaf rust fungus, Puccinia triticina, were obtained in 2017 from agricultural experiment station plots, demonstration plots, and farm fields in the Great Plains, the Ohio Valley, the southeastern states, California, and Washington in order to determine the prevalent virulence phenotypes present in the United States. A total of 65 virulence phenotypes were identified among the 469 single uredinial isolates that were tested on 20 near-isogenic lines of Thatcher wheat that differ for leaf rust resistance genes. Virulence phenotypes MBTNB at 11.3% of the overall population, and MCTNB at 7.0%, were the first and third most common phenotypes. Both phenotypes were found mostly in the southeastern states and Ohio Valley region. Phenotype TFTSB at 10.9% was the second most common phenotype and was found mostly in southern Texas. Virulence to leaf rust resistance gene Lr39, which is present in hard red winter wheat cultivars, was highest in the Great Plains region. Virulence to Lr11 and Lr18, which are present in soft red winter wheat cultivars, was highest in the southeastern states and Ohio Valley region. Virulence to Lr21, which is present in hard red spring wheat cultivars, was highest in the northern Great Plains region. The predominate P. triticina phenotypes from the soft red winter wheat regions of the southeastern states and Ohio Valley area differed from those in the hard red winter and hard red spring wheat areas of the Great Plains region. Collections from Washington had unique virulence phenotypes that had not been previously detected.
GAPIN: Grouped and Aligned Protein Interface Networks
Authors: Araújo Biharck M. , Coelho Aline L. , Silveira Sabrina A. , Romanelli João P. R. , de Melo-Minardi Raquel C. , da Silveira Carlos H.
Published: March 2019

GAPIN is a web-based application for structural interaction network analysis among any type of PDB molecules, regardless of whether their interfaces are between chain-chain or chain-ligand. A special emphasis is given to graph clustering, allowing users to scrutinize target contexts for ligand candidates. We show how GAPIN can be used to unveil underlying hydrophobic patterns on a set of peptidase-inhibitor complexes. In another experiment, we show there is a positive correlation between cluster sizes and the presence of druggable spots, indicating that the clustering may discriminate the higher complexity of these hot subnetworks.

Availability and implementation

GAPIN is freely available as an easy-to-use web interface at https://gapin.unifei.edu.br.

Contact

biharck@ufmg.br, carlos.silveira@unifei.edu.br.

Supplementary information

Supplementary data are available online.
RanBP2/Nup358 enhances miRNA activity by sumoylating and stabilizing Argonaute 1
Authors: Shen Qingtang , Wang Yifan E. , Truong Mathew , Mahadevan Kohila , Wu Jing Ze , Smith Harrison W. , Smibert Craig , Palazzo Alexander F.
Published: March 2019

RanBP2/Nup358 is one of the main components of the cytoplasmic filaments of the nuclear pore complex. It has been speculated that RanBP2, which has an E3 SUMO-ligase domain, may alter the composition of messenger ribonucleoprotein (mRNP) complexes as they emerge from the nuclear pore and thus regulate the ultimate fate of the mRNA in the cytoplasm. Four separate missense mutations in RanBP2 cause Acute Necrotizing Encephalopathy 1 (ANE1), which manifests as a sharp rise in cytokine production after common viral infections such as influenza and parainfluenza. However, how RanBP2 and its ANE1-associated mutations affect cytokine production is not well understood. Here we report that RanBP2 represses the translation of the interleukin-6 (IL6) mRNA, which encodes a cytokine that is aberrantly up-regulated in ANE1. Our data indicates that soon after its production, the IL6 mRNP recruits the RNA-induced silencing complex (RISC) bound to Let7 miRNA. After this mRNP is exported, RanBP2 sumoylates the RISC-component AGO1, thereby stabilizing it and enforcing mRNA silencing. Collectively, these results support a model whereby RanBP2 promotes an mRNP remodelling event that is critical for the miRNA-mediated suppression of clinically relevant mRNAs, such as IL6.
Radiation resistant cancer cells enhance the survival and resistance of sensitive cells in prostate spheroids
Authors: Kannan Pavitra , Paczkowski Marcin , Miar Ana , Owen Joshua , Kretzschmar Warren W. , Lucotti Serena , Kaeppler Jakob , Chen Jianzhou , Markelc Bostjan , Kunz-Schughart Leoni A. , Harris Adrian L. , Partridge Mike , Byrne Helen
Published: March 2019

Intratumoural heterogeneity contributes to local tumour recurrence and variable responses to radiotherapy in prostate cancer. Despite the multiclonal nature of the disease, tumour control probability for conventional treatment plans is modelled on the assumption that tumour cells in the target region respond identically and independently. Here, using tumour cell subpopulations with different radiation sensitivities from prostate tumour cell lines, we show that radiation resistant cells enhance the survival and radiation resistance of radio-sensitive cells in spheroids but not in monolayer culture. Mathematical modelling indicates that these phenotypic changes result from both competitive and antagonistic cellular interactions in spheroids. Interactions mediated by oxygen constraints define the spatial localisation of the cell populations in spheroids and in xenografts, while those mediated by paracrine signals further modify the microenvironment. Our results show new mechanisms of radiotherapy resistance mediated by cellular interactions and by the microenvironment.
On Pectin Methyl-esterification: Implications forIn vitroandIn vivoViscoelasticity
Authors: Kaplan J.L. , Torode T.A. , Bou Daher F. , Braybrook S.A.
Published: March 2019

Pectin is a major component of the primary plant cell wall and is important for cell expansion. However, the relationship between its chemistry and mechanical properties is not fully understood, especiallyin vivo. In this study, a protocol for viscoelastic micro-indentation using atomic force microscopy (AFM) was developed and applied to pectinin vitroandin vivo. After determining that linear viscoelasticity was a suitable theoretical framework forin vitropectin analyses were conducted with both a standard linear solid and fractional Zener model. These indicated a strong coupling between elastic and viscous properties over a range of degrees of methyl-esterification (DM). Both elasticity and viscosity were found to vary non-linearly with DM which had interesting consequences for pectin gels of mixed DM. InArabidopsiscell walls, the standard linear solid model was found to be appropriate. In thisin vivocomposite material a weaker elastic-viscous coupling was exhibited, correlated with DM. The viscoelastic testingin vivoof rapidly elongating cell walls, rich in high DM pectin, displayed a longer viscous time-scale. The implications of the testing method and results are discussed in the context of mechanobiology, mechano-chemistry, and cell growth.
Galanin neurons in the hypothalamus link sleep homeostasis, body temperature and actions of the α2 adrenergic agonist dexmedetomidine
Authors: Ma Ying , Miracca Giulia , Yu Xiao , Harding Edward C. , Miao Andawei , Yustos Raquel , Vyssotski Alexei L. , Franks Nicholas P. , Wisden William
Published: March 2019

Sleep deprivation induces a characteristic rebound in NREM sleep accompanied by an immediate increase in the power of delta (0.5 - 4 Hz) oscillations, proportional to the prior time awake. To test the idea that galanin neurons in the mouse lateral preoptic hypothalamus (LPO) regulate this sleep homeostasis, they were selectively genetically ablated. The baseline sleep architecture of LPO-ΔGal mice became heavily fragmented, their average core body temperature permanently increased (by about 2°C) and the diurnal variations in body temperature across the sleep-wake cycle also markedly increased. Additionally, LPO-ΔGal mice showed a striking spike in body temperature and increase in wakefulness at a time (ZT24) when control mice were experiencing the opposite - a decrease in body temperature and becoming maximally sleepy (start of “lights on”). After sleep deprivation sleep homeostasis was largely abolished in LPO-ΔGal mice: the characteristic increase in the delta power of NREM sleep following sleep deprivation was absent, suggesting that LPO galanin neurons track the time spent awake. Moreover, the amount of recovery sleep was substantially reduced over the following hours. We also found that the α2 adrenergic agonist dexmedetomidine, used for long-term sedation during intensive care, requires LPO galanin neurons to induce both the NREM-like state with increased delta power and the reduction in body temperature, characteristic features of this drug. This suggests that dexmedetomidine over-activates the natural sleep homeostasis pathway via galanin neurons. Collectively, the results emphasize that NREM sleep and the concurrent reduction in body temperature are entwined at the circuit level.

Significance

Catching up on lost sleep (sleep homeostasis) is a common phenomenon in mammals, but there is no circuit explanation for how this occurs. We have discovered that galanin neurons in the hypothalamus are essential for sleep homeostasis as well as for the control of body temperature. This is the first time that a neuronal cell type has been identified that underlies sleep homeostasis. Moreover, we show that activation of these galanin neurons are also essential for the actions of the α2 adrenergic agonist dexmedetomidine, which induces both hypothermia together with powerful delta oscillations resembling NREM sleep. Thus, sleep homeostasis, temperature control and sedation by α2 adrenergic agonists can all be linked at the circuit level by hypothalamic galanin neurons.
An interplay between reaction-diffusion and cell-matrix adhesion regulates multiscale invasion in early breast carcinomatosis
Authors: Pally Dharma , Pramanik Durjay , Bhat Ramray
Published: March 2019

The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodelled during the process. A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells can be arrived at through the construction of increasingly complex experimental and computational models. Herein, we introduce a multiscale 3D organo-and patho-typic model that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics. End-point and time-lapse microscopic observations of this model allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments. We then construct an agent-based Cellular Potts model that incorporates constituents of the experimental model, as well as places them in similar spatial arrangements. The computational model, which comprises adhesion between cancer cells and the matrices, cell proliferation and apoptosis, and matrix remodeling through reaction-diffusion-based morphogen dynamics, is first trained to phenocopy controls run with the experimental model, wherein one or the other matrices have been removed. The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density). Our results suggest that specific permissive regimes of cell-cell and cell-matrix adhesions operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which they migrate through their surrounding stroma.
The Personal Genome Project-UK: an open access resource of human multi-omics data
Authors: Chervova Olga , Conde Lucia , Guerra-Assunção José Afonso , Moghul Ismail , Webster Amy P. , Berner Alison , Cadieux Elizabeth Larose , Tian Yuan , Voloshin Vitaly , Hamoudi Rifat , Herrero Javier , Beck Stephan
Published: March 2019

Integrative analysis of multi-omics data is a powerful approach for gaining functional insights into biological and medical processes. Conducting these multifaceted analyses on human samples is often complicated by the fact that the raw sequencing output is rarely available under open access. The Personal Genome Project UK (PGP-UK) is one of few resources that recruits its participants under open consent and makes the resulting multi-omics data freely and openly available. As part of this resource, we describe the PGP-UK multi-omics reference panel consisting of ten genomic, methylomic and transcriptomic data. Specifically, we outline the data processing, quality control and validation procedures which were implemented to ensure data integrity and exclude sample mix-ups. In addition, we provide a REST API to facilitate the download of the entire PGP-UK dataset. The data are also available from two cloud-based environments, providing platforms for free integrated analysis. In conclusion, the genotype-validated PGP-UK multi-omics human reference panel described here provides a valuable new open access resource for integrated analyses in support of personal and medical genomics.
Injectable nanoclay gels for angiogenesis
Authors: Page Daniel J. , Clarkin Claire E. , Mani Raj , Khan Najeed A. , Dawson Jonathan I. , Evans Nicholas D.
Published: March 2019

The retention and sustained activity of therapeutic proteins at delivery sites are goals of regenerative medicine. Vascular endothelial growth factor (VEGF) has significant potential in promoting the growth and regeneration of blood vessels but is intrinsically labile. This is exacerbated by the inflammatory microenvironments at sites requiring regeneration. For VEGF to be efficacious it may require a carrier that stabilises it, protects it from degradation and retains it at a site of interest. In this study we tested the hypothesis that injectable nanoclay gels composed of Laponite XLG can stabilise VEGF and retain it in active form for therapeutic delivery. To achieve this, VEGF was incorporated in Laponite gels and its activity tested at a range of concentrations using in vivo cell culture tubulogenesis assays and in vivo angiogenesis assays. We found that VEGF-Laponite gels enhanced tubulogenesis in a dose-dependent manner in vivo. When administered subcutaneously in vivo Laponite was retained at an injection site for up to a period of three weeks and promoted a 4-fold increase in blood vessel formation compared with alginate or vehicle controls as confirmed by CD31 staining. Notably, in contrast to alginate, Laponite gels did not release VEGF, indicating a strong interaction between the growth factor and the nanoclay, and suggesting that Laponite enhancement of VEGF efficacy is due to its retention at an implantation site over a prolonged period. Our approach provides a robust method for delivery of bioactive recombinant VEGF without the necessity for complex hydrogel or protein engineering.
Norepinephrine controls the gain of the inhibitory circuit in the cerebellar input layer
Authors: Lanore Frederic , Rothman Jason S. , Coyle Diccon , Silver R. Angus
Published: March 2019

Golgi cells (GoCs) are the main inhibitory interneurons in the input layer of the cerebellar cortex and are electrically coupled together, forming syncytia. GoCs control the excitability of granule cells (GCs) through feedforward, feedback and spillover-mediated inhibition. The GoC circuit therefore plays a central role in determining how sensory and motor information is transformed as it flows through the cerebellar input layer. Recent work has shown that GCs are activated when animals perform active behaviours, but the underlying mechanisms remain poorly understood. Norepinephrine (NE), also known as noradrenaline, is a powerful modulator of network function during active behavioral states and the axons of NE-releasing neurons in the locus coeruleus innervate the cerebellar cortex. Here we show that NE hyperpolarizes the GoC membrane potential, decreases spontaneous firing and reduces the gain of the spike frequency versus input-current relationship. The GoC membrane hyperpolarization can be mimicked with an α2-noradrenergic agonist, inhibited with a specific α2 antagonist and is abolished when G protein-coupled inwardly-rectifying potassium (GIRK) channels are blocked. Moreover, NE reduces the effective electrical coupling between GoCs through a persistent sodium current (INaP)-dependent mechanism. Our results suggest that NE controls the gain of the GoC inhibitory circuit by modulating membrane conductances that act to reduce membrane excitability and decrease electrical coupling. These mechanisms appear configured to reduce the level of GoC inhibition onto GCs during active behavioural states.
Manipulation of gut microbiota during critical developmental windows affects host physiological performance and disease susceptibility across ontogeny
Authors: Warne Robin W. , Kirschman Lucas , Zeglin Lydia
Published: March 2019

Colonization of gut microbiomes during early life can shape metabolism and immunity of adult animals. However, most data are derived from antibiotic‐treated or germ‐free laboratory mammals. Furthermore, few studies have explored how microbial colonization during critical windows influences a suite of other fitness‐related traits in wild animals.

This study tested whether hatching constitutes a critical developmental window for gut microbiome colonization in wild‐caught amphibians and whether perturbations to gut microbiota at hatching shape fitness‐related traits of larval growth, metabolism, metamorphosis and disease susceptibility.

We sterilized wood frog eggs and then inoculated them with microbes from differing sources, including from another species (bullfrogs) that differ in disease resistance and life history. We measured development, growth and metabolic rates through metamorphosis among individuals from each microbial treatment. A separate group was exposed to an LD50 dose of ranavirus—an emerging disease—to test for microbiome effects on disease susceptibility. We also quantified rates of deformities to test for microbial treatment effects on overall health.

Manipulation of microbiota on eggs altered the trajectory of gut microbiome communities across larval ontogeny, though disruption appeared to be transitory. While microbiome structure converged among the treatments by metamorphosis, the effects of disruption on host phenotypes persisted. Larvae inoculated with the bullfrog gut microbiota exhibited accelerated growth and development rates compared to controls. By contrast, sterilized larvae maintained in sterile water for several days after hatching exhibited greater disruption to their gut microbiota across ontogeny, as well as altered metabolism, more tail deformities, and were more likely to die when exposed to an LD50 dose of ranavirus compared to the other treatments.

These results suggest perturbations to the microbiota during critical developmental windows can alter the trajectory of the gut microbiome, and have long‐term effects on fitness‐related traits in larval amphibians. These results suggest that explicit tests of how changes in the composition and abundance of the microbial community shape phenotypes across ontogeny in amphibians could shed light on host–microbe interactions in wildlife, as well as inform conservation efforts to mitigate emerging diseases.
Work done in the margins: A comparative study of mental health literacy in pre‐service teacher education in Australia and in Scotland
Authors: Armstrong David , Macleod Gale , Brough Colin
Published: March 2019

Ensuring pre‐service teachers have strong mental health literacy is vital for progress towards an inclusive, effective education system; yet little is known about how pre‐service teachers are prepared for practice with school students who present with poor mental health. The original, internationally comparative small‐scale (N = 24) qualitative study reported here compared current mental health literacy provision to pre‐service teacher education students in Scotland and Australia. Semi‐structured telephone interviews with teacher educators who delivered mental health content divulged highly variable, often ad‐hoc mental health literacy provision; a concern, given the prevalence of poor mental health affecting children and young people in schools. Thematic data analysis revealed striking commonalities among issues raised by participants from both countries, highlighting the need for urgent improvement in the provision of mental health literacy to pre‐service teachers. Results suggest the possibility of strategically developing a joint Australian‐Scottish mental health component suitable for delivery in both countries.
Amylose: Acetylation, Optimization, and Characterization
Authors: Tang Hongbo , Fan Shaofeng , Li Yanping , Dong Siqing
Published: March 2019

Amylose, as a polymeric carbohydrate, is a very attractive raw material owing to its performances. However, the acetylation of amylose separated from high amylose corn starch (HACS) will be beneficial to further improve its functional characteristics so that acetylated amylose (AA) is able to be well applied for some special situations. In this work, we chiefly discuss the optimization of acetylation conditions by a response surface methodology, property, and characterization of AA. The experimental results indicated that the acetylation of amylose was affected by some factors, such as reaction temperature, reaction time, amount of acetic anhydride, and pH. The blue value of amylose was changed by acetylation. Maltese crosses on the separated amylose particles disappeared owing to the separation. The crystalline structure of HACS was C‐type, whereas the structure of AA was the immediate between B‐ and V‐type. The acetylation lowered the onset temperature, peak temperature, and end temperature of amylose, but raised its melting enthalpy.

Practical Application

Although inherent functional diversity of starch extracted from different biological sources adds to the range of applications, acetylated amylose, as an additive, will be better control the consistency and texture of some foods, enhance the strength of edible films, and improve the slow‐release of drugs. It will also provide options for extending the scope of desired functional characteristics.
Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence‐based practice, an international approach
Authors: Lieberman Lani , Greinacher Andreas , Murphy Michael F. , Bussel James , Bakchoul Tamam , Corke Stacy , Kjaer Mette , Kjeldsen‐Kragh Jens , Bertrand Gerald , Oepkes Dick , Baker Jillian M. , Hume Heather , Massey Edwin , Kaplan Cécile , Arnold Donald M. , Baidya Shoma , Ryan Greg , Savoia Helen , Landry Denise , Shehata Nadine ,   the International Collaboration for Transfusion Medicine Guidelines (ICTMG)
Published: March 2019

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may result in severe bleeding, particularly fetal and neonatal intracranial haemorrhage (ICH). As a result, FNAIT requires prompt identification and treatment; subsequent pregnancies need close surveillance and management. An international panel convened to develop evidence‐based recommendations for diagnosis and management of FNAIT. A rigorous approach was used to search, review and develop recommendations from published data for: antenatal management, postnatal management, diagnostic testing and universal screening. To confirm FNAIT, fetal human platelet antigen (HPA) typing, using non‐invasive methods if quality‐assured, should be performed during pregnancy when the father is unknown, unavailable for testing or heterozygous for the implicated antigen. Women with a previous child with an ICH related to FNAIT should be offered intravenous immunoglobulin (IVIG) infusions during subsequent affected pregnancies as early as 12 weeks gestation. Ideally, HPA‐selected platelets should be available at delivery for potentially affected infants and used to increase the neonatal platelet count as needed. If HPA‐selected platelets are not immediately available, unselected platelets should be transfused. FNAIT studies that optimize antenatal and postnatal management, develop risk stratification algorithms to guide management and standardize laboratory testing to identify high risk pregnancies are needed.
Skiing Simulation Based on Skill‐Guided Motion Planning
Authors: Hu Chen‐Hui , Lee Chien‐Ying , Liou Yen‐Ting , Sung Feng‐Yu , Lin Wen‐Chieh
Published: March 2019

Skiing is a popular recreational sport, and competitive skiing has been events at the Winter Olympic Games. Due to its wide moving range in the outdoor environment, motion capture of skiing is hard and usually not a good solution for generating skiing animations. Physical simulation offers a more viable alternative. However, skiing simulation is challenging as skiing involves many complicated motor skills and physics, such as balance keeping, movement coordination, articulated body dynamics and ski‐snow reaction. In particular, as no reference motions — usually from MOCAP data — are readily available for guiding the high‐level motor control, we need to synthesize plausible reference motions additionally. To solve this problem, sports techniques are exploited for reference motion planning. We propose a physics‐based framework that employs kinetic analyses of skiing techniques and the ski–snow contact model to generate realistic skiing motions. By simulating the inclination, angulation and weighting/unweighting techniques, stable and plausible carving turns and bump skiing animations can be generated. We evaluate our framework by demonstrating various skiing motions with different speeds, curvature radii and bump sizes. Our results show that employing the sports techniques used by athletes can provide considerable potential to generate agile sport motions without reference motions.
Synthesis of a di‐(p‐sulphophenoxy)‐s‐triazine reactive dye and its application in wool fabric ink‐jet printing
Authors: Yang Kai , Clark Matthew , Lewis David M.
Published: March 2019

Reactive dyes based on p‐sulphophenoxy‐s‐triazines were synthesised, characterised and applied to wool fabric by ink‐jet printing. The extent of dye‐fibre covalent bonding (% fixation) was measured on prints produced using different development methods. The most promising method to obtain high dye‐fibre fixation values was to interleave the printed wool with a pre‐wetted cotton fabric and store for 3 h. Steam fixation was also investigated but gave lower fixation values. The degree of dye hydrolysis vs time in the ink formulation was evaluated because ink stability is critical in commercial operation; a reformulated ink based on a phosphate buffer was found to improve ink stability.
Strength of forest edge effects on litter‐dwelling macro‐arthropods across Europe is influenced by forest age and edge properties
Authors: De Smedt Pallieter , Baeten Lander , Proesmans Willem , Van de Poel Sam , Van Keer Johan , Giffard Brice , Martin Ludmilla , Vanhulle Rieneke , Brunet Jörg , Cousins Sara A.O. , Decocq Guillaume , Deconchat Marc , Diekmann Martin , Gallet‐Moron Emilie , Le Roux Vincent , Liira Jaan , Valdés Alicia , Wulf Monika , Andrieu Emilie , Hermy Martin , Bonte Dries , Verheyen Kris
Published: March 2019

Aim

Forests are highly fragmented across Western Europe, making forest edges important features in many agricultural landscapes. Forest edges are subject to strong abiotic gradients altering the forest environment and resulting in strong biotic gradients. This has the potential to change the forest's capacity to provide multiple ecosystem services such as nutrient cycling, carbon sequestration and natural pest control. Soil organisms play a key role in this perspective; however, these taxa are rarely considered in forest edge research.

Location

A latitudinal gradient of 2,000 km across Western Europe.

Methods

We sampled six dominant taxa of litter‐dwelling macro‐arthropods (carabid beetles, spiders, harvestmen, centipedes, millipedes and woodlice) in forest edges and interiors of 192 forest fragments in 12 agricultural landscapes. We related their abundance and community composition to distance from the edge and the interaction with forest age, edge orientation and edge contrast (contrast between land use types at either side of the edge).

Results

Three out of six macro‐arthropod taxa have higher activity‐density in forest edges compared to forest interiors. The abundance patterns along forest edge‐to‐interior gradients interacted with forest age. Forest age and edge orientation also influenced within‐fragment compositional variation along the forest edge‐to‐interior gradient. Edge contrast influenced abundance gradients of generalist predators. In general, older forest fragments, south‐oriented edges and edges along structurally more continuous land use (lower contrast between forest and adjacent land use) resulted in stronger edge‐to‐interior gradients while recent forests, north‐oriented edges and sharp land use edges induced similarity between forest edge and interior along the forest edge‐to‐interior gradients in terms of species activity‐density and composition.

Main conclusions

Edge effects on litter‐dwelling macro‐arthropods are anticipated to feedback on important ecosystem services such as nutrient cycling, carbon sequestration and natural pest control from small forest fragments.
Range area matters, and so does spatial configuration: predicting conservation status in vertebrates
Authors: Lucas Pablo M. , González‐Suárez Manuela , Revilla Eloy
Published: March 2019

The current rapid loss of biodiversity globally calls for improved tools to predict conservation status. Conservation status varies among taxa and is influenced by intrinsic species’ traits and extrinsic factors. Among these predictors, the most consistently recognized and widely available is geographic range area. However, ranges of equal area can have diverse spatial configurations that reflect variation in threatening processes and species’ characteristics (e.g. dispersal ability), and can affect local and regional population dynamics. The aim of this study is to assess if and how the spatial configuration of a species’ range relates to its conservation status. We obtained range maps and two descriptors of conservation status: extinction risk and population trend, from the IUCN for 11 052 species of amphibians, non‐marine birds and terrestrial mammals distributed across the World. We characterized spatial configuration using descriptors of shape and fragmentation (fragment number and size heterogeneity) and used regression analysis to evaluate their role in explaining current extinction risk and population trend. The most important predictor of conservation status was range area, but our analyses also identified shape and fragmentation as valuable predictors. We detected complex relationships, revealed by multiple interaction terms, e.g. more circular shapes were negatively correlated with population trend, and heterogeneity was positively correlated with extinction risk for small range areas but negatively for bigger ranges. Considering descriptors of spatial configuration beyond size improves our understanding of conservation status among vertebrates. The metrics we propose are relatively easy to define (although values can be sensitive to data quality), and unlike other correlates of status, like species’ traits, are readily available for many species (all of those with range maps). We argue that considering spatial configuration predictors is a straightforward way to improve our capacity to predict conservation status and thus, can be useful to promote more effective conservation.
Dynamic cell type‐specific expression of Nrf2 after traumatic brain injury in mice
Authors: Dong Wenwen , Sun Yingfu , Cheng Hao , Yang Bei , Wang Linlin , Jiang Zhenfei , Li Bingxuan , Wen Shuheng , Guo Xiangshen , Guan Dawei , Zhao Rui
Published: March 2019

Nrf2 plays a pivotal role in antioxidant response and anti‐inflammation after traumatic brain injury (TBI), and its deletion aggravates TBI‐induced brain damage. Previous studies have demonstrated that Nrf2 is activated post TBI, but dynamic changes in expression and cell type‐specific characteristics remain unclear. In this study, the Feeney weight‐drop contusion model was conducted to mimic TBI, and the ipsilateral cerebral cortex was collected at 1, 3, 7 and 14 days post TBI (dpi). Nrf2 protein levels were observed by western blot. Cell type‐specific localization of Nrf2 after TBI was detected at different time intervals by double immunofluorescence staining. NeuN, GFAP, IBA1 and NG2 were used as cell type‐specific markers to neurons, astrocytes, microglia and NG2 glia, respectively. After TBI, Nrf2 protein levels peaked at 1 dpi. Robust transient Nrf2 accumulation was co‐localized with neurons, which was predominant at 1 dpi. Continuous weak Nrf2 expression was detected in activated astrocytes, and the number of double positive cells peaked at 7 dpi. Inducible widespread immunostaining of Nrf2 was observed in the nucleus of the microglia, and the number of Nrf2+ microglia peaked at 7 dpi. In addition, we also explored colocalization of Nrf2 in NG2 glia, in which the percentage of Nrf2+ in NG2 glia reached a climax at 3 dpi. This study reveals that the accumulation of endogenous Nrf2 might mediate different pathophysical roles in neurons and glias after TBI, the cell‐type specific and time‐dependent expression provide insights to explain the roles of Nrf2 in different neural cells.
Tarsal arthrodesis in horses
Authors: Auer J. A. , Fürst A. E.
Published: March 2019

In this commentary, first the do's and don'ts of arthrodesis are discussed followed by a description of the different techniques of partial tarsal arthrodesis. Specific comments were made to discuss the case report in this issue by Vlahos (2019) with regards to the plate positioning and at the end some thoughts on pantarsal arthrodesis in adult horses are presented.
Coauthorship Practices, Motivations, and Ethical Applications in Clothing and Textiles Research
Authors: Lee Seung‐Eun (Joy) , Lee Jaeil
Published: March 2019

The researchers investigated coauthorship practices, motivations, and ethical applications among clothing and textiles (C&T) researchers. An email invitation was sent to all registered members of the International Textiles and Apparel Association (ITAA) with a URL for accessing the survey. Most of the 80 participants were tenured or tenure‐track faculty members in the United States who had published an average of five coauthored articles in the past 5 years. The findings showed that C&T researchers engaged in coauthorship primarily to improve the overall quality of their work by combining complementary skills and pursuing joint ideas and common interests. The overall contribution to the manuscript was the primary rule that was used to determine the order of listing authors. Although they were generally satisfied with their most recent coauthorship experience, some researchers had experienced problems with inappropriate authorship. The findings of this study suggest the need to formulate guidelines related to coauthorship and order of authorship in publishing research in C&T.