bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of neuronal anatomy and circuitry in two highly divergent nematode species
Authors: Hong Ray L. , Riebesell Metta , Bumbarger Daniel J. , Cook Steven J. , Carstensen Heather R. , Sarpolaki Tahmineh , Cochella Luisa , Castrejon Jessica , Moreno Eduardo , Sieriebriennikov Bogdan , Hobert Oliver , Sommer Ralf J.
Published: April 2019

The nematodesC. elegansandP. pacificuspopulate diverse habitats and display distinct patterns of behavior. To understand how their nervous systems have diverged, we undertook a detailed examination of the neuroanatomy of the chemosensory system ofP. pacificus. Using independent features such as cell body position, axon projections and lipophilic dye uptake, we have assigned homologies between the amphid neurons, their first-layer interneurons, and several internal receptor neurons ofP. pacificusandC. elegans.We found that neuronal number and soma position are highly conserved. However, the morphological elaborations of several amphid cilia are different between them, most notably in the absence of ‘winged’ cilia morphology inP. pacificus. We established a synaptic wiring diagram of amphid sensory neurons and amphid interneurons inP. pacificusand found striking patterns of conservation and divergence in connectivity relative toC. elegans, but very little changes in relative neighborhood of neuronal processes.

Impact Statement

The substrate for evolutionary divergence does not lie in changes in neuronal cell number or targeting, but rather in sensory perception and synaptic partner choice within invariant, prepatterned neuronal processes.
FGF signalling regulates enhancer activation during ear progenitor induction
Authors: Tambalo Monica , Anwar Maryam , Ahmed Mohi , Streit Andrea
Published: April 2019

The fibroblast growth factor pathway is essential for inner ear induction in many vertebrates, however how it regulates the chromatin landscape to coordinate the activation of otic genes remains unclear. Here we show that FGF exposure of sensory progenitors leads to rapid deposition of active chromatin marks H3K27ac near hundreds of FGF-responsive, otic-epibranchial progenitor (OEP) genes, while H3K27ac is depleted in the vicinity of non-otic genes. Genomic regions that gain H3K27ac act as cis-regulatory elements controlling OEP gene expression in time and space and define a unique transcription factor signature likely to control their activity. Finally, we provide evidence that in response to FGF signalling the transcription factor dimer AP1 recruits the histone acetyl transferase p300 to OEP enhancers and that de novo acetylation is required for subsequent expression of OEP genes. Thus, during ear induction FGF signalling modifies the chromatin landscape to promote enhancer activation and chromatin accessibility.
Complete genome sequence and annotation of the laboratory reference strainShigella flexneriserotype 5a M90T and genome-wide transcriptional start site determination
Authors: Cervantes-Rivera Ramón , Tronnet Sophie , Puhar Andrea
Published: April 2019

Background

Shigellais a Gram-negative facultative intracellular bacterium that causes bacillary dysentery in humans.Shigellainvades cells of the colonic mucosa owing to its virulence plasmid-encoded Type 3 Secretion System (T3SS), and multiplies in the target cell cytosol. Although the laboratory reference strainS. flexneriserotype 5a M90T has been extensively used to understand the molecular mechanisms of pathogenesis, its complete genome sequence is not available, thereby greatly limiting studies employing high-throughput sequencing and systems biology approaches.

Results

We have sequenced, assembled, annotated and manually curated the full genome ofS. flexneri5a M90T. This yielded two complete circular contigs, the chromosome and the virulence plasmid (pWR100). To obtain the genome sequence, we have employed long-read PacBio DNA sequencing followed by polishing with Illumina RNA-seq data. This provides a new pipeline to prepare gapless, highly accurate genome sequences. Furthermore, we have performed genome-wide analysis of transcriptional start sites and determined the length of 5’ untranslated regions (5’-UTRs) at typical culture conditions for the inoculum ofin vitroinfection experiments. We identified 6,723 primary TSS (pTSS) and 7,328 secondary TSS (sTSS). TheS. flexneri5a M90T annotated genome sequence and the transcriptional start sites are integrated into RegulonDB (http://regulondb.ccg.unam.mx) and RSAT (http://embnet.ccg.unam.mx/rsat/) to use its analysis tools inS. flexneri5a M90T genome.

Conclusions

We provide the first complete genome forS. flexneriserotype 5a, specifically the laboratory reference strain M90T. Our work opens the possibility of employingS. flexneriM90T in high-quality systems biology studies such as transcriptomic and differential expression analyses or in genome evolution studies. Moreover, the catalogue of TSS that we report here can be used in molecular pathogenesis studies as a resource to know which genes are transcribed before infection of host cells. The genome sequence, together with the analysis of transcriptional start sites, is also a valuable tool for precise genetic manipulation ofS. flexneri5a M90T. The hybrid pipeline that we report here combining genome sequencing with long-reads technology and polishing with RNAseq data defines a powerful strategy for genome assembly, polishing and annotation in any type of organism.
Gene expression heterogeneity during brain development and aging: temporal changes and functional consequences
Authors: Işıldak Ulaş , Somel Mehmet , Thornton Janet M. , Dönertaş Handan Melike
Published: April 2019

Cells in largely non-mitotic tissues such as the brain are prone to stochastic (epi-)genetic alterations that may cause increased variability between cells and individuals over time. Although increased inter-individual heterogeneity in gene expression was previously reported, whether this process starts during development or if it is restricted to the aging period has not yet been studied. The regulatory dynamics and functional significance of putative aging-related heterogeneity are also unknown. Here we address these by a meta-analysis of 19 transcriptome datasets from diverse human brain regions. We observed a significant increase in inter-individual heterogeneity during aging (20+ years) compared to postnatal development (0 to 20 years). Increased heterogeneity during aging was consistent among different brain regions at the gene level and associated with lifespan regulation and neuronal functions. Overall, our results show that increased expression heterogeneity is a characteristic of aging human brain, and may influence aging-related changes in brain functions.
Optimal decoding of NFkB signaling dynamic
Authors: Maity Alok , Wollman Roy
Published: April 2019

The encoder/decoder paradigm suggests that signaling networks transform information about the extracellular environment into specific signaling patterns that are then read by downstream effectors to control cellular behavior. Previous work used information theoretical tools to analyze the fidelity of encoding using dynamic signaling patterns. However, as the overall fidelity depends on both encoding and decoding, it is important to consider information loss during signal decoding. Here we used NFkB signaling as a model to understand the accuracy of signal decoding. Using a detailed mathematical model we simulated realistic NFkB signaling patterns with different degrees of variability. The NFkB patterns were used as an input to a simple gene expression model. Analysis of information transmission between ligand and NFkB and ligand and gene expression allow us to determine information loss in both encoding and decoding steps. Information loss could occur due to biochemical noise or due to lack of specificity in decoding response. We found that noise free decoding has very little information loss suggesting that decoding through gene expression can preserve specificity in NFkB patterns. As expected, information transmission through a noisy decoder suffers from information loss. Interestingly, this effect can be mitigated by a specific choice of decoding parameters that can substantially reduce information loss due to biochemical noise during signal decoding. Overall our results show that optimal decoding of dynamic patterns can preserve ligand specificity to maximize the accuracy of cellular response to environmental cues.

Synopsis

The fidelity of signal transduction depends on the accurate encoding of ligand information in specific signaling patterns and the reliable decoding of these patterns by downstream gene expression machinery. We present an analysis of the accuracy of decoding processes in the case of the transcription factor NFkB. We show that noiseless decoding can preserve ligand identity with minimal information loss. Noisy decoding does result in information loss, an effect that can be largely mitigated by choice of optimal decoding parameter values.

Decoding of dynamic signaling patterns by a simple gene model can preserve most of the information about ligand identity.

Noisy decoding will result in information loss, but this effect can be mitigated by the optimal choice of decoding parameters.

Improvement in decoding is a result of decreased variability in gene expression patterns.
Mask family proteins ANKHD1 and ANKRD17 regulate YAP nuclear import, stability and phase separation
Authors: Sidor Clara , Borreguero-Munoz Nerea , Fletcher Georgina C , Elbediwy Ahmed , Vanyai Hannah , Guillermin Oriane , Thompson Barry J
Published: April 2019

The Mask family of multiple ankyrin repeat and KH domain proteins were discovered in Drosophila to promote the activity of the transcriptional coactivator Yorkie (Yki), the sole fly homolog of mammalian YAP (YAP1) and TAZ (WWTR1). The molecular function of Mask, or its mammalian homologs Mask1 (ANKHD1) and Mask2 (ANKRD17), remains unclear. Mask family proteins contain two Ankyrin repeat domains that bind Yki/YAP as well as a conserved nuclear localisation sequence (NLS) and nuclear export sequence (NES), suggesting a role in nucleo-cytoplasmic transport. Here we show that Mask acts to promote nuclear import of Yki, and that addition of an ectopic NLS to Yki is sufficient to bypass the requirement for Mask in Yki-driven tissue growth. Mammalian Mask1/2 proteins also promote nuclear import of YAP, as well as stabilising YAP and driving colloidal phase separation into large liquid droplets. Mask1/2 and YAP normally colocalise in a granular fashion in both nucleus and cytoplasm, and are co-regulated during mechanotransduction. Our results suggest that Mask family proteins promote YAP nuclear import and phase separation to regulate YAP stability and transcriptional activity.
Complementary roles for parvalbumin and somatostatin interneurons in the generation of hippocampal gamma oscillations
Authors: Antonoudiou Pantelis , Tan Yu Lin , Kontou Georgina , Upton A. Louise , Mann Edward O.
Published: April 2019

Gamma-frequency oscillations (30-120 Hz) can be separated into fast (>60 Hz) and slow oscillations, with different roles in neuronal encoding and information transfer. While synaptic inhibition is important for synchronization across the gamma-frequency range, the role of distinct interneuronal subtypes in fast and slow gamma states remains unclear. Here, we used optogenetics to examine the involvement of parvalbumin (PV+) and somatostatin (SST+) expressing interneurons in gamma oscillations in the mouse hippocampal CA3 ex vivo. Disrupting either PV+ or STT+ interneuron activity, via either photo-inhibition or photo-excitation, led to a decrease in the power of cholinergically-induced slow gamma oscillations. Furthermore, photo-excitation of SST+ interneurons induced fast gamma oscillations, which depended on both synaptic excitation and inhibition. Our findings support a critical role for both PV+ and SST+ interneurons in slow hippocampal gamma oscillations, and further suggest that STT+ interneurons are capable of switching the network between slow and fast gamma states.
Optimization of a Modular Steroid-Inducible Gene Expression System for Use in Rice
Authors: Vlad Daniela , Samalova Marketa , Abu-Jamous Basel , Wang Peng , Moore Ian R. , Langdale Jane A.
Published: April 2019

Chemically inducible systems that provide both spatial and temporal control of gene expression are essential tools, with many applications in plant biology. Using Golden Gate modular cloning, we have created a monocot-optimized dexamethasone (DEX)-induciblepOp6/LhGR system and tested its efficacy in rice using the reporter enzyme β-glucuronidase (GUS). The system is tightly regulated and highly sensitive to DEX application, with six hours of induction sufficient to induce high levels of GUS activity in transgenic callus. In seedlings, GUS activity was detectable in the root afterin vitroapplication of just 0.01μM DEX. However, transgenic plants manifested severe developmental perturbations when grown on higher concentrations of DEX. The direct cause of these growth defects is not known, but the rice genome contains sequences with high similarity to the LhGR target sequencelacO, suggesting non-specific activation of endogenous genes by DEX induction. These off-target effects can be minimized by quenching with isopropyl β-D-1-thiogalactopyranoside (IPTG). The system is thus suitable for general use in rice, when the method of DEX application and relevant controls are tailored appropriately for each specific application.
Circular RNA circGTIC1 drives gastric TIC self-renewal to initiate gastric tumorigenesis and metastasis
Authors: Wang Liyan , Li Bin , Xiao Xuhua , Yi Xiaoyuan , He Feifei
Published: April 2019

The authors have withdrawn this manuscript because the experiment was badly designed and the results could not be repeated. Therefore, the authors do not wish this work to be cited as reference for the project.
TLR-induced reorganization of the IgM-BCR complex regulates B-1 cell responses to infections
Authors: Savage Hannah P. , Kläsener Kathrin , Smith Fauna L. , Luo Zheng , Reth Michael , Baumgarth Nicole
Published: April 2019

Neonatally-developing, self-reactive B-1 cells generate steady levels natural antibodies throughout life. They can, however, also rapidly respond to infections with increased local antibody production. The mechanisms regulating these two seemingly very distinct functions are poorly understood, but have been linked to expression of CD5, an inhibitor of BCR-signaling. Here we demonstrate that TLR-mediated activation of CD5+ B-1 cells induced the rapid reorganization of the IgM-BCR complex, leading to the eventual loss of CD5 expression, and a concomitant increase in BCR-downstream signaling, bothin vitroandin vivoafter infections with influenza virus andSalmonella typhimurium. Both, initial CD5 expression and TLR-mediated stimulation, were required for the differentiation of B-1 cells to IgM-producing plasmablasts after infections. Thus, TLR-mediated signals support participation of B-1 cells in immune defense via BCR-complex reorganization.
Brian 2: an intuitive and efficient neural simulator
Authors: Stimberg Marcel , Brette Romain , Goodman Dan F. M.
Published: April 2019

To 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

AMPylation 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 Statement

Unique 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 Points

The 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

Cellular 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

Background

Vascular 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.

Methods

In 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.

Results

Expression 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.

Conclusions

The 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

Nucleolus-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

Human-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.
Pancreatic cyst fluid harboring a KRAS mutation
Authors: Al-Turkmani M. Rabie , Gordon Stuart R. , Smith Kerrington D. , Tsongalis Gregory J. , Liu Xiaoying
Published: April 2019

A 55-yr-old woman presented with abdominal bloating for approximately 1 year. Imaging studies showed a cyst in the body of the pancreas with proximal pancreatic ductal dilation. An endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed. Cytologic findings from the cyst fluid were consistent with a mucinous neoplastic cyst, and the possibility of malignancy could not be entirely excluded. A KRAS mutation analysis was performed on the cyst fluid using the Idylla system and circulating tumor KRAS (ctKRAS) cartridge (Biocartis, Mechelen, Belgium), which tests for actionable mutations in exons 2, 3, and 4 of the KRAS gene. Idylla testing detected a KRAS G12D mutation in the cyst fluid. The patient subsequently underwent a distal subtotal pancreatectomy with splenectomy. Microscopic examination of the resected tissue revealed an intraductal papillary mucinous neoplasm (IPMN) with an associated invasive carcinoma. KRAS testing on the resected tumor tissue confirmed the G12D mutation detected in the cyst fluid earlier. The described rapid testing of KRAS directly from the pancreatic cyst fluid can complement cytology assessment to classify pancreatic cysts more reliably and can potentially be of significant help when other cyst findings are nondiagnostic.
Isolation of High-Molecular-Weight DNA from Mouse Tail Tips
Authors: Behringer Richard , Gertsenstein Marina , Nagy Kristina Vintersten , Nagy Andras
Published: April 2019

DNA samples are prepared from mouse tail tips by Proteinase K digestion and subsequently extracted. The resulting preparation is suitable for use in Southern blotting or polymerase chain reaction (PCR).
RNAi in Drosophila S2 Cells by siRNA Duplex or dsRNA Transfection
Authors: Li Chengjian , Zamore Phillip D.
Published: April 2019

This protocol describes an efficient method to trigger RNAi in Drosophila S2 cells by using transfection reagents to deliver siRNAs or dsRNAs.
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

Purpose

This 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/approach

A 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.

Findings

In 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 implications

The accumulation of knowledge and actionable clues in this study is expected to keep practitioners updated with the overwhelming volume of ICT research.

Originality/value

This 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.
Sexualization of the work environment and emotional exhaustion
Authors: Bui Hong T.M. , Pinto Jonathan , Srivastava Abhishek
Published: April 2019

Purpose

The purpose of this paper is to explore the relationship between sexualization of the work environment and emotional exhaustion, and develop some key antecedents of sexualization of the work environment. It was conducted in an emerging society, India, which has a high rate of crime against women, particularly related to sexual harassment and sexual assault.

Design/methodology/approach

To test the hypotheses, structural equation modeling was performed. The hypotheses were tested with data from 1,098 white collar workers in India in three ways.

Findings

Contact with other gender and flexible work arrangements were positively associated with sexualization of the work environment; and sexualization of the work environment was positively associated with emotional exhaustion. In addition, sexualization of the work environment mediated the relationship between the two antecedent variables and emotional exhaustion.

Research limitations/implications

There is a possible bias arising from the use of cross-sectional data. However, a number of methods were implemented to minimize it, including survey design and data analysis.

Practical implications

The study offers some important suggestions for workplaces with a greater proportion of young male employees, particularly in a societal context like India.

Originality/value

The paper provides evidence of the negative impact of sexualization of the work environment, and thereby contributes to current understanding of the “dark side” of behavior at work that might have significant impact on society.
Influence of ambidextrous governance mechanisms and risk management on repurchase intention in social commerce
Authors: Cheng Jao Hong , Lin Li Wei , Lee Liang Chien
Published: April 2019

Purpose

The purpose of this paper is to examine the factors influencing ambidextrous governance and risk management on repurchase intention in social commerce.

Design/methodology/approach

A novel research model comprises nine research hypotheses with six constructs, including three dimensions of social capital (structural, relational and cognitive), contracts, relational risk and repurchase intention. The hypotheses are tested on data collected from 395 usable responses in Taiwan, using structural equation modeling.

Findings

The findings of this study indicate that online merchants should reinforce their collaborative behavior and activities to improve ambidextrous governance mechanisms, and thus enhance repurchase intention.

Research limitations/implications

The resultant findings only reflect the setting of Taiwan’s social commerce marketplace. With the research model developed, future research on cross-country studies of various forms of social networking sites would be worth conducting to determine regional differences in the development of social commerce activities.

Originality/value

Ambidextrous governance mechanisms have been gaining attention in buyer–supplier relationships. Extending ambidexterity research to the social commerce domain, the authors focus on ambidextrous governance that can include social and contractual governance elements.
Tactile sensing for surgical and collaborative robots and robotic grippers
Authors: Bogue Robert
Published: April 2019

Purpose

This paper aims to illustrate the increasingly important role played by tactile sensing in robotics by considering three specific fields of application.

Design/methodology/approach

Following a short introduction, this paper first provides details of tactile sensing principles, technologies, products and research. The following sections consider tactile sensing applications in robotic surgery, collaborative robots and robotic grippers. Finally, brief conclusions are drawn.

Findings

Tactile sensors are the topic of an extensive and technologically diverse research effort, with sensing skins attracting particular attention. Many products are now available commercially. New generations of surgical robots are emerging which use tactile sensing to provide haptic feedback, thereby eliminating the surgeon’s total reliance on visual control. Many collaborative robots use tactile and proximity sensing as key safety mechanisms and some use sensing skins. Some skins can detect both human proximity and physical contact. Sensing skins that can be retrofitted have been developed. Commercial tactile sensors have been incorporated into robotic grippers, notably anthropomorphic types, and allow the handling of delicate objects and those with varying shapes and sizes. Tactile sensing uses will inevitably increase because of the ever-growing numbers of robots interacting with humans.

Originality/value

This study provides a detailed account of the growing use of tactile sensing in robotics in three key areas of application.
Internet and prevalence of relative thinking
Authors: Thota Sweta Chaturvedi , Kinra Ritwik
Published: April 2019

Purpose

Research demonstrates that individuals display relative thinking – the tendency to consider relative savings rather than just absolute savings in their decisions to search for a deal or purchase an item. This paper aims to review empirical and analytical literature on relative thinking, perceived search costs and price savings to propose and test a conceptual model of relative thinking.

Design/methodology/approach

Through two studies, the paper tests whether individuals display relative thinking when shopping across stores vs online and how they perceive search and time spent in pursuing savings. Both studies are adaptations of the classic jacket-and-calculator scenario study (Tversky and Kahneman, 1981).

Findings

Results show attenuation of the robust relative thinking phenomenon over the internet compared to shopping across stores. Individuals exhibit increased price sensitivity for both low and high relative savings conditions on the internet but demonstrate price sensitivity only in the high relative savings condition in the store shopping contexts. Diagnostic measures pertaining to the attractiveness of savings and the perceptions of search costs corroborate the support for relative thinking across stores but not over the internet.

Originality/value

These results lend weight to the central claim in this paper that the internet marks a new boundary condition for the relative thinking phenomenon in marketing literature. Theoretical and managerial implications of the findings, the limitations of the studies and future research opportunities are discussed.
Participative leadership and job satisfaction
Authors: Chan Simon C.H.
Published: April 2019

Purpose

The purpose of this paper is twofold: first, to examine the relationships between participative leadership and employees’ work engagement and job satisfaction; and second, to determine whether the level of fun experienced at work moderates the effect of participative leadership on job satisfaction.

Design/methodology/approach

The participants were 177 employees in a retailing store in Hong Kong. Hierarchical multiple regression was conducted with the control variables to ascertain the relationships among participative leadership, level of fun experienced at work, work engagement and job satisfaction.

Findings

The results indicated that participative leadership was positively related to employees’ work engagement and job satisfaction. Employees’ work engagement mediated the relationship between participative leadership and job satisfaction. This positive relationship between participative leadership and job satisfaction was stronger when employees had more fun at work.

Research limitations/implications

The generalizability of the data was limited, as the characteristics of participants in a retail store are distinct from others in the service industry.

Practical implications

This paper’s findings imply that participative leaders can engage in role modeling by providing more fun workplace activities to employees, which will increase their work engagement and job satisfaction.

Originality/value

The findings help to explain the relationship between participative leadership and job satisfaction, provide a better understanding of leadership management styles and show that participative leaders who engage employees in fun activities in the workplace can increase employees’ job satisfaction.