bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brian 2: an intuitive and efficient neural simulator
Authors: Stimberg Marcel , Brette Romain , Goodman Dan F. M. 
Published: April 2019

AbstractTo be maximally useful for neuroscience research, neural simulators must make it possible to define original models. This is especially important because a computational experiment might not only need descriptions of neurons and synapses, but also models of interactions with the environment (e.g. muscles), or the environment itself. To preserve high performance when defining new models, current simulators offer two options: low-level programming, or mark-up languages (and other domain specific languages). The first option requires time and expertise, is prone to errors, and contributes to problems with reproducibility and replicability. The second option has limited scope, since it can only describe the range of neural models covered by the ontology. Other aspects of a computational experiment, such as the stimulation protocol, cannot be expressed within this framework. “Brian” 2 is a complete rewrite of Brian that addresses this issue by using runtime code generation with a procedural equation-oriented approach. Brian 2 enables scientists to write code that is particularly simple and concise, closely matching the way they conceptualise their models, while the technique of runtime code generation automatically transforms high level descriptions of models into efficient low level code tailored to different hardware (e.g. CPU or GPU). We illustrate it with several challenging examples: a plastic model of the pyloric network of crustaceans, a closed-loop sensorimotor model, programmatic exploration of a neuron model, and an auditory model with real-time input from a microphone.
An oligomeric state-dependent switch in FICD regulates AMPylation and deAMPylation of the chaperone BiP
Authors: Perera Luke A. , Rato Claudia , Yan Yahui , Neidhardt Lisa , McLaughlin Stephen H. , Read Randy J. , Preissler Steffen , Ron David 
Published: April 2019

AbstractAMPylation is an inactivating modification that matches the activity of the major endoplasmic reticulum (ER) chaperone BiP to the burden of unfolded proteins. A single ER-localised Fic protein, FICD (HYPE), catalyses both AMPylation and deAMPylation of BiP. However, the basis for the switch in FICD’s activity is unknown. We report on the transition of FICD from a dimeric enzyme, that deAMPylates BiP, to a monomer with potent AMPylation activity. Mutations in the dimer interface or in residues tracing an inhibitory relay from the dimer interface to the enzyme’s active site favour BiP AMPylation in vitro and in cells. Mechanistically, monomerisation relieves a repressive effect allosterically-propagated from the dimer interface to the inhibitory Glu234, thereby permitting AMPylation-competent binding of MgATP. Whereas, a reciprocal signal propagated from the nucleotide binding site, provides a mechanism for coupling the oligomeric-state and enzymatic activity of FICD to the energy status of the ER.Impact StatementUnique amongst known chaperones, the endoplasmic reticulum (ER)-localized Hsp70, BiP, is subject to transient inactivation under conditions of low ER stress by reversible, covalent modification – AMPylation. The enzyme responsible for this modification, FICD, is in fact a bifunctional enzyme with a single active site capable of both AMPylation and deAMPylation. Here we elucidate, by biochemical, biophysical and structural means, the mechanism by which this enzyme is able to switch enzymatic modality: by regulation of its oligomeric state. The oligomeric state-dependent reciprocal regulation of FICD activity is, in turn, sensitive to the ATP/ADP ratio. This allosteric pathway potentially facilitates the sensing of unfolded protein load in the ER and permits the transduction of this signal into a post-translational buffering of ER chaperone activity.
Post-translational polymodification of β1 tubulin regulates motor protein localisation in platelet production and function
Authors: Khan Abdullah O. , Slater Alexandre , Maclachlan Annabel , Nicolson Phillip L.R. , Pike Jeremy A. , Reyat Jasmeet S. , Yule Jack , Stapley Rachel , Thomas Steven G. , Morgan Neil V. 
Published: April 2019

In specialised cells, the expression of specific tubulin isoforms and their subsequent post-translational modifications drive and coordinate unique morphologies and behaviours. The mechanisms by which β1 tubulin, the platelet and megakaryocyte (MK) lineage restricted tubulin isoform, drives platelet production and function remains poorly understood. We investigated the roles of two key post-translational polymodifications (polyglutamylation and polyglycylation) on these processes using a cohort of thrombocytopenic patients, human induced pluripotent stem cell (iPSC) derived MKs, and healthy human donor platelets. We find distinct patterns of polymodification in MKs and platelets, mediated by the antagonistic activities of the cell specific expression of Tubulin Tyrosine Ligase Like (TTLLs) and Cytosolic Carboxypeptidae (CCP) enzymes. The resulting microtubule patterning spatially regulates motor proteins to drive proplatelet formation in megakaryocytes, and the cytoskeletal reorganisation required for thrombus formation. This work is the first to show a reversible system of polymodification by which different cell specific functions are achieved.Key PointsThe platelet specific β1 tubulin (encoded by TUBB1) is polymodified (polyglutamylated and polyglycylated) in platelet producing iPSC-derived megakaryocytes (MKs), this patterning spatially regulates motor proteins, and its disruption in TUBB1 patient variants results in a loss of platelet production.A system of reversible polymodifications mediated through the graded expression of modifying enzymes (TTLLs and CCPs) throughout MK maturation is required for proplatelet formation and subsequent platelet function.
Muscle fiber hypertrophy in response to 6 weeks of high-volume resistance training in trained young men is largely attributed to sarcoplasmic hypertrophy
Authors: Haun Cody T. , Vann Christopher G. , Osburn Shelby C. , Mumford Petey W. , Roberson Paul A. , Romero Matthew A. , Fox Carlton D. , Johnson Christopher A. , Parry Hailey A. , Kavazis Andreas N. , Moon Jordan R. , Badsia Veera L.D. , Mwashote Benjamin M. , Ibeanusi Victor , Young Kaelin C. , Roberts Michael D. 
Published: April 2019

ABSTRACTCellular adaptations that occur during skeletal muscle hypertrophy in response to high-volume resistance training are not well-characterized. Therefore, we sought to explore how actin, myosin, sarcoplasmic protein, mitochondrial, and glycogen concentrations were altered in individuals that exhibited mean skeletal muscle fiber cross-sectional area (fCSA) hypertrophy following 6 weeks of high-volume resistance training. Thirty-one previously resistance-trained, college-aged males (mean ± standard deviation: 21±2 years, 5±3 training years) had vastus lateralis (VL) muscle biopsies obtained prior to training (PRE), at week 3 (W3), and at week 6 (W6). Muscle tissue from 15 subjects exhibiting PRE to W6 VL mean fCSA increases ranging from 320-1600 μm2 was further interrogated using various biochemical and histological assays as well as proteomic analysis. Seven of these individuals donated a VL biopsy after refraining from training 8 days following the last training session (W7) to determine how deloading affected biomarkers. The 15 fCSA hypertrophic responders experienced a +23% increase in mean fCSA from PRE to W6 (p<0.001) and, while muscle glycogen concentrations remained unaltered, citrate synthase activity levels decreased by 24% (p<0.001) suggesting mitochondrial volume decreased. Interestingly, both myosin and actin concentrations decreased ~30% from PRE to W6 (p<0.05). Phalloidin-actin staining similarly revealed actin concentrations per fiber decreased from PRE to W6. Proteomic analysis of the sarcoplasmic fraction from PRE to W6 indicated 40 proteins were up-regulated (p<0.05), KEGG analysis indicated that the glycolysis/gluconeogenesis pathway was upregulated (FDR sig. <0.001), and DAVID indicated that the following functionally-annotated pathways were upregulated (FDR value <0.05): a) glycolysis (8 proteins), b) acetylation (23 proteins), c) gluconeogenesis (5 proteins) and d) cytoplasm (20 proteins). At W7, sarcoplasmic protein concentrations remained higher than PRE (+66%, p<0.05), and both actin and myosin concentrations remained lower than PRE (~−50%, p<0.05). These data suggest that short-term high-volume resistance training may: a) reduce muscle fiber actin and myosin protein concentrations in spite of increasing fCSA, and b) promote sarcoplasmic expansion coincident with a coordinated up-regulation of sarcoplasmic proteins involved in glycolysis and other metabolic processes related to ATP generation. Interestingly, these effects seem to persist up to 8 days following training.
VEGF and FGF signaling during head regeneration in hydra
Authors: Turwankar Anuprita , Ghaskadbi Surendra 
Published: April 2019

AbstractBackgroundVascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) signaling pathways play important roles in the formation of the blood vascular system and nervous system across animal phyla. We have earlier reported VEGF and FGF from Hydra vulgaris Ind-Pune, a cnidarian with a defined body axis, an organized nervous system and a remarkable ability of regeneration. We have now identified three more components of VEGF and FGF signaling pathways from hydra. These include FGF-1, FGF receptor 1 (FGFR-1) and VEGF receptor 2 (VEGFR-2) with a view to deciphering their possible roles in regeneration.MethodsIn silico analysis of proteins was performed using Clustal omega, Swiss model, MEGA 7.0, etc. Gene expression was studied by whole mount in situ hybridization. VEGF and FGF signaling was inhibited using specific pharmacological inhibitors and their effects on head regeneration were studied.ResultsExpression patterns of the genes indicate a possible interaction between FGF-1 and FGFR-1 and also VEGF and VEGFR-2. Upon treatment of decapitated hydra with pharmacological inhibitor of FGFR-1 or VEGFR-2 for 48 hours, head regeneration was delayed in treated as compared to untreated, control regenerates. When we studied the expression of head specific genes HyBra1 and HyKs1 and tentacle specific gene HyAlx in control and treated regenerates using whole mount in situ hybridization, expression of all the three genes was found to be adversely affected in treated regenerates.ConclusionsThe results suggest that VEGF and FGF signaling play important roles in regeneration of hypostome and tentacles in hydra.
Different localization of fluorescently labeled N- and C-termini of nucleolin variants in human glioblastoma cell culture
Authors: Panteleev Dmitri , Pustogarov Nikolai , Revishchin Alexander , Shamadykova Dzhirgala , Drozd Sergey , Goryanov Sergey , Potapov Alexander , Pavlova Galina 
Published: April 2019

AbstractNucleolus-oriented protein nucleolin plays a significant role in the life of a normal mammalian cell. However, nucleolin is also actively expressed in cells of malignant tumors. At the same time, its expression in different types of cancer is significantly increased compared with normal cells. It is interesting that nucleolin localization often varies in tumor cells, namely in the cytoplasm and on the cell membrane. This fact is considered to be a poor prognostic indicator. This work is devoted to the study of the distribution of nucleolin in human glioblastoma cells. Glioblastoma is one of the most aggressive malignant tumors with an absolutely unfavorable prognosis. These tumors have a high proliferative potential, but in addition they are often characterized by invasive properties. Research on lineage cells does not let to fully study these properties of glioblastoma, since lineage cells are very different from the actual tumor. In our study, we used two primary cell cultures of human glioblastoma with varying degrees of invasiveness of the original tumors. The main interest was directed at studying the localization of nucleolin and its correlation with the invariability of the N- and C-termini of the corresponding protein. Particular attention was paid to the significance of the unaltered C-terminus of nucleolin for its distribution in the cells of transplanted human glioblastoma cultures derived from patient tissues.The aim of this work is to find the relationship between the deformation of the N- or C-terminal sequences of nucleolin and its localization.We showed that in glioblastoma cells, with a high degree of invasion, nucleolin is found in the cytoplasm and close to the cell membrane, and the distribution of nucleolin with undeformed C and N-terminal does not match.
The human-specific paralogs SRGAP2B and SRGAP2C differentially modulate SRGAP2A-dependent synaptic development
Authors: Schmidt Ewoud R.E. , Kupferman Justine V. , Stackmann Michelle , Polleux Franck 
Published: April 2019

AbstractHuman-specific gene duplications (HSGD) have recently emerged as key modifiers of brain development and evolution. However, the molecular mechanisms underlying the function of HSGDs remain often poorly understood. In humans, a truncated duplication of SRGAP2A led to the emergence of two human-specific paralogs: SRGAP2B and SRGAP2C. The ancestral copy SRGAP2A limits synaptic density and promotes maturation of both excitatory (E) and inhibitory (I) synapses received by cortical pyramidal neurons (PNs). SRGAP2C binds to and inhibits all known functions of SRGAP2A leading to an increase in E and I synapse density and protracted synapse maturation, traits characterizing human cortical neurons. Here, we demonstrate how the evolutionary changes that led to the emergence of SRGAP2 HSGD generated proteins that, in neurons, are intrinsically unstable and upon hetero-dimerization with SRGAP2A, reduces SRGAP2A levels in a proteasome-dependent manner. Moreover, we show that, compared to SRGAP2B, and despite only a few non-synonymous mutations specifically targeting arginine residues, SRGAP2C is unique, compared to SRGAP2B, in its ability to induce long-lasting changes in synaptic density throughout adulthood. The non-synonymous mutations specifically targeting arginine residues led to the unique ability of SRGAP2C to inhibit SRGAP2A function and thereby contribute to the emergence of human-specific features of synaptic development during evolution.
Igni18, a novel metallo-hydrolase from the hyperthermophilic archaeon Ignicoccus hospitalis KIN4/I: cloning, expression, purification and X-ray analysis
Authors: Kobus Stefanie , Perez-Garcia Pablo , Hoeppner Astrid , Holzscheck Nicholas , Kovacic Filip , Streit Wolfgang R. , Jaeger Karl-Erich , Chow Jennifer , Smits Sander H. J. 
Published: April 2019

The hyperthermophilic crenarchaeon Ignicoccus hospitalis KIN4/I possesses at least 35 putative genes encoding enzymes that belong to the α/β-hydrolase superfamily. One of those genes, the metallo-hydrolase-encoding igni18, was cloned and heterologously expressed in Pichia pastoris. The enzyme produced was purified in its catalytically active form. The recombinant enzyme was successfully crystallized and the crystal diffracted to a resolution of 2.3 Å. The crystal belonged to space group R32, with unit-cell parameters a = b = 67.42, c = 253.77 Å, α = β = 90.0, γ = 120.0°. It is suggested that it contains one monomer of Igni18 within the asymmetric unit.
Rethinking the rationale of open and distance education: a case of the UK Open University
Authors: Jeong Hanmo 
Published: April 2019

Purpose
The purpose of this paper is to describe how the introduction of new technologies has affected student support at the United Kingdom Open University (UKOU) particularly focusing on face-to-face tutorials and online tutorials, what this impact implies for open universities and in what direction the innovations toward the sustainability of open universities should proceed.

Design/methodology/approach
Research on the historical development of UKOU and a literature review was conducted.

Findings
The rationale behind the foundation of UKOU has been to provide higher education to those who have time and physical constraints. There is no doubt that the introduction of advanced technologies has played a significant role in the growth of the university. However, when the university attempted to replace face-to-face tutorials with online tutorials on the basis of its purpose, a number of students and faculty members opposed the decision even though online tutorials fit within its original objective. This paper suggests that face-to-face tutorials have become the essence of the university through the process of identifying the university in the past and the university’s identity may need to be distinguished from the rationale.

Originality/value
This paper emphasizes the necessity of rethinking the Open and Distance Education rationale and, on the basis of past studies on UKOU, offers a unique perspective about the changes that have taken place at the university.
Disparities in the provision of aging-friendly communities in old and new urban neighborhoods in China
Authors: Yu Jingyu , Ma Guixia , Cai Shaoxing 
Published: April 2019

Purpose
Aging-friendly environments have been encouraged to develop at the city level, district level and community level in China. In the process of rapid urbanization, the state of aging-friendly communities in old and new neighborhoods is disparate. Hence, the purpose of this paper is to investigate aging-friendly communities and identify the disparities in old and new neighborhoods.

Design/methodology/approach
A total of 1,172 elderly respondents completed the survey. Of these, 576 seniors lived in an old community developed before 2000, and 596 lived in a new community developed after 2000. In total, 17 physical environment factors and 10 social environment factors were identified.

Findings
The results indicated that public spaces, facilities and transportation in old neighborhoods were inferior to those in new neighborhoods. Most social environment factors in new neighborhoods achieved higher satisfaction levels than those in old neighborhoods. The satisfaction levels of aging-friendly community factors in both old and new neighborhoods were below the expectation levels of elders.

Practical implications
In order to improve physical aging-friendly environments in old neighborhoods, it is suggested that full use is made of school facilities and the renovation of old buildings. The locations of public transportation stations in new neighborhoods are recommended to be revised within 5-min walking distances of senior residents. Both old and new neighborhoods are encouraged to improve social aging-friendly environments by increasing the coverage of medical services and creating multiple approaches to recreation activities.

Originality/value
These findings have empirical significance for urban planners and policy makers, in regard to identifying disparities between old and new neighborhoods, and understanding the equitable allocation and distribution of urban resources.
Progression and development of information and communication technology research in hospitality and tourism
Authors: Law Rob , Leung Daniel , Chan Irene Cheng Chu 
Published: April 2019

PurposeThis study aims to present a state-of-the art review on information and communication technology (ICT) research in hospitality and tourism published between 2014 and 2017.Design/methodology/approachA total of 288 full-length articles from eight top-tier hospitality and tourism journals were gathered by harnessing a systematic literature search approach. Subsequently, the authors used a qualitative content analysis to review, analyse and assign all included articles into a framework with six consumer-related and five supplier-related research streams.FindingsIn terms of volume (i.e. the amounts and ratios of ICT research in top-tier journals by publication year) and variety (i.e. the diversity of research topics), a significant progression of ICT research in hospitality and tourism is observed. However, some old and new knowledge gaps are still inadequately addressed, thus requiring scholars and practitioners to conduct additional research in the future.Practical implicationsThe accumulation of knowledge and actionable clues in this study is expected to keep practitioners updated with the overwhelming volume of ICT research.Originality/valueThis study contributes to the literature by accelerating the accumulation of knowledge on research topics and setting forth an agenda for future research. The findings also complement prior literature reviews by providing an overview of how knowledge on ICT research in hospitality and tourism has progressed since 2014.
Testing a criticality framework for road networks in Auckland, New Zealand
Authors: Rebello Kester , Jaggi Karan , Costello Seosamh , Blake Daniel , Oo May , Hughes James , Egbelakin Temitope 
Published: April 2019

Purpose
The purpose of this paper is to trial the application of a criticality framework for roads in an urban environment. The failure or disruption of critical transport routes can have substantial impacts on the economy and societal well-being. Determining the criticality of transport routes is thus of crucial importance for infrastructure providers, city planners and emergency management officials, as it enables appropriate resilience assessments and targeted improvement/intervention and investment strategies to be conducted.

Design/methodology/approach
The authors summarise the proposed criticality framework developed by Hughes (2016) for road networks and apply and validate the framework to an area containing 907 km of roads in the central Auckland area of New Zealand. Following an initial trial of the framework, alterations were made to the framework logic, which included the introduction of a new criticality level to account for some roads providing minimal direct societal and economic benefit and a rationalisation step to ensure that road sections always link to others with either an equal or higher criticality.

Findings
The modified framework and five-level criticality scale, when applied to the study area in central Auckland, is suitable for determining critical roads and can therefore assist with future assessments of road infrastructure resilience.

Originality/value
The framework also has the potential to be applied more widely and adapted so that it is applicable for determining the criticality of other infrastructure types and in other settings, which would allow improved assessments within and across sectors.