bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractSummaryGAPIN 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 implementationGAPIN is freely available as an easy-to-use web interface at https://gapin.unifei.edu.br.Contactbiharck@ufmg.br, carlos.silveira@unifei.edu.br.Supplementary informationSupplementary 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

SUMMARYRanBP2/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

ABSTRACTIntratumoural 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

AbstractPectin 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

AbstractSleep 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.SignificanceCatching 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.
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

AbstractIntegrative 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

AbstractThe 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

SummaryGolgi 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

Abstract

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

AbstractAmylose, 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 ApplicationAlthough 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

AbstractFetal 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

AbstractSkiing 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.