bluuebunny/crossref_metadata_2025 huggingface dataset:
Substrate specificity of SARS-CoV-2 nsp10-nsp16 methyltransferase
Authors: Benoni Roberto , Krafcikova Petra , Baranowski Marek R. , Kowalska Joanna , Boura Evzen , Cahová Hana
Published: July 2020

The ongoing COVID-19 pandemic exemplifies the general need to better understand viral infections. The positive single strand RNA genome of its causative agent, the SARS coronavirus 2 (SARS-CoV-2) encodes all viral enzymes. In this work, we focus on one particular methyltransferase (MTase), nsp16, which in complex with nsp10 is capable of methylating the first nucleotide of a capped RNA strand at the 2′-O position. This process is part of a viral capping system and is crucial for viral evasion of the innate immune reaction. In light of recently discovered non-canonical RNA caps, we tested various dinucleoside polyphosphate-capped RNAs as substrates for nsp10-nsp16 MTase. We developed an LC-MS-based method and discovered five types of capped RNA (m7Gp3A(G)-, Gp3A(G)- and Gp4A-RNA) that are substrates of the nsp10-nsp16 MTase. Our technique is an alternative to the classical isotope labelling approach for measurement of 2′-O-MTase activity. Further, we determined the IC50value of sinefungin (286 ± 66 nM) to illustrate the value of our approach for inhibitor screening. In the future, this approach can be used for screening inhibitors of any type of 2′-O-MTase.
Helicase-Like Functions in Phosphate Loop Containing Beta-Alpha Polypeptides
Authors: Vyas Pratik , Trofimyuk Olena , Longo Liam M. , Deshmukh Fanindra Kumar , Sharon Michal , Tawfik Dan S.
Published: July 2020

The P-loop Walker A motif underlies hundreds of essential enzyme families that bind nucleotide triphosphates (NTPs) and mediate phosphoryl transfer (P-loop NTPases), including the earliest DNA/RNA helicases, translocases and recombinases. What were the primordial precursors of these enzymes? Could these large and complex proteins emerge from simple polypeptides? Previously, we showed that P-loops embedded in simple βα repeat proteins bind NTPs, but also, unexpectedly so, ssDNA and RNA. Here, we extend beyond the purely biophysical function of ligand binding to demonstrate rudimentary helicase-like activities. We further constructed simple 40-residue polypeptides comprising just one β-(P-loop)-α element. Despite their simplicity, these P-loop prototypes confer functions such as strand separation and exchange. Foremost, these polypeptides unwind dsDNA, and upon addition of NTPs, or inorganic polyphosphates, release the bound ssDNA strands to allow reformation of dsDNA. Binding kinetics and low-resolution structural analyses indicate that activity is mediated by oligomeric forms spanning from dimers to high-order assemblies. The latter are reminiscent of extant P-loop recombinases such as RecA. Overall, these P-loop prototypes comprise a plausible description of the sequence, structure and function of the earliest P-loop NTPases. They also indicate that multifunctionality and dynamic assembly were key in endowing short polypeptides with elaborate, evolutionarily relevant functions.

Significance statement

It is widely assumed that today’s large and complex proteins emerged from much shorter and simpler polypeptides. Yet the nature of these early precursors remains enigmatic. We describe polypeptides that contain one of the earliest protein motifs, a phosphate-binding loop, or P-loop, embedded in a single beta-alpha element. These P-loop prototypes show intriguing characteristics of a primordial world comprised of nucleic acids and peptides. They are ‘generalists’ capable of binding different phospho-ligands, including inorganic polyphosphates and single-stranded DNA. Nonetheless, in promoting double-stranded DNA unwinding and strand-exchange they resemble modern P-loop helicases and recombinases. Our study describes a missing link in the evolution of complex proteins – simple polypeptides that tangibly relate to contemporary P-loop enzymes in sequence, structure and function.
Light induced changes in starry flounder (Platichthys stellatus) opsin expression and its influence on vision estimated from a camouflage-based behavioural assay
Authors: Iwanicki Tom , Haman Cliff , Liu Amy , Taylor John S.
Published: July 2020

Correlations between variation in opsin expression and variation in vision are often assumed but rarely tested. We exposed starry flounder (Platichthys stellatus) to either broad spectrum sunlight or green-filtered light in outdoor aquaria for seven weeks and then combined digital-PCR and camouflage experiments to test two hypotheses: i) short-wavelength sensitive opsin expression decreases in a green light environment, and ii) if observed, this change in opsin expression influences colour vision as estimated using a camouflage-based behavioural assay. Of the eight visual opsins measured,Sws1(UV sensitive) andSws2B(blue sensitive) expression was significantly lower in fish exposed to green light. However, opsin expression in fish transferred to an arena illuminated with white LED light for three hours after the green light treatment did not differ from broad spectrum controls. Changes in opsin expression in response to artificial light environments have been reported before, but rapid changes over three hours rather than days or weeks is unprecedented. We did not observe a significant difference in a flounder’s camouflage response based on light environment, although broad spectrum fish increased and green-filter fish decreased the pattern contrast when on the blue-green substrate, and this difference approached significance. This pattern is intriguing considering green-filter fish expressed fewer UV and blue opsins and we recommend increased statistical power for future experiments. Together, our results show that starry flounder opsin expression changes rapidly in response to changes in light environment, however, there is no apparent effect on their visually mediated camouflage.
Perception of and anxiety about COVID-19 infection and risk behaviors for spreading infection: An international comparison
Authors: Shiina Akihiro , Niitsu Tomihisa , Kobori Osamu , Idemoto Keita , Hashimoto Tasuku , Sasaki Tsuyoshi , Igarashi Yoshito , Shimizu Eiji , Nakazato Michiko , Hashimoto Kenji , Iyo Masaomi
Published: July 2020

To control the spread of the newly developed corona viral infection diseases (COVID-19), people’s appropriate precautionary behaviors should be promoted. We conducted a series of online questionnaire survey, to gather a total of 8,000 citizen’s responses on March 27–28, 2020 in Japan and April 17–21 in the UK and Spain. Compared to Japan, the knowledge and anxiety level and the frequency of precautionary behaviors were higher in the UK and Spain. Participants with infected acquaintances were more concerned about COVID-19. However, participants in the UK rarely wore a medical mask. Participants in the UK and Spain were eager to get information about COVID-19 compared to those in Japan. The participants in Spain tended not to trust official information and to believe specialists' comments instead. The urgency of the spread of COVID-19, cultural backgrounds, and recent political situations appear to contribute to the differences among countries revealed herein.
Epigenetic suppression of SLFN11 in germinal center B cells in the process of the dynamic expression change during B-cell development
Authors: Moribe Fumiya , Nishikori Momoko , Sasanuma Hiroyuki , Akagawa Remi , Arima Hiroshi , Takeda Shunichi , Takaori-Kondo Akifumi , Murai Junko
Published: July 2020

Background

SLFN11 enhances cellular toxicity of genotoxic anti-cancer agents, and its important role under physiological conditions has not been appreciated yet. Somatic hypermutations and class switch recombination that can cause physiological genotoxic stress arise in germinal center B cells (GCBs). GCBs are a major origin of B-cell lymphomas that are frequently treated by cytosine arabinoside, a genotoxic anti-cancer agent.

Objective

To clarify the expression profile ofSLFN11in different stages of B cells and B-cell lymphomas.

Methods

We analyzed the expression ofSLFN11by mining publicly available databases for different stages of normal B cells and various types of B-cell lymphoma lines and also by performing immunohistochemical staining of human lymph nodes. We investigated the effects of two epigenetic modifiers, an EZH2 inhibitor, tazemetostat (EPZ6438) and a histone deacetylase inhibitor, panobinostat (LBH589) onSLFN11expression in B-cell lymphoma lines and examined the therapeutic efficacy of these epigenetic modifiers in the combination with cytosine arabinoside.

Results

SLFN11expression was specifically low in GCBs compared to non-GCBs, which was consolidated by the immunohistochemical staining for SLFN11 with human lymph nodes.SLFN11expression levels in B-cell lymphoma lines largely correlated to those of their normal counterparts. The epigenetic modifiers upregulatedSLFN11expression in GCB-derived lymphomas and made the lymphomas further susceptible to cytosine arabinoside.

Conclusions

The expression ofSLFN11may be epigenetically suppressed in GCBs and GCB-derived lymphomas. GCB-derived lymphomas with lowSLFN11expression can be treated by the combination of epigenetic modifiers and cytosine arabinoside.
Increases in whole brain grey matter associated with long-term Sahaja Yoga Meditation: a detailed area by area description
Authors: Hernández Sergio Elías , Dorta Roberto , Suero José , Barros-Loscertales Alfonso , González-Mora José Luis , Rubia Katya
Published: July 2020

Objectives

Our previous study showed that long-term practitioners of Sahaja Yoga Meditation (SYM) had around 7% larger grey matter volume (GMV) in the whole brain compared with healthy controls; however, when testing individual regions, only 5 small brain areas were statistically different between groups. Under the hypothesis that those results were statistically conservative, with the same dataset, we investigated in more detail the regional differences in GMV associated with the practice of SYM, with a different statistical approach.

Design

Twenty-three experienced practitioners of SYM and 23 healthy non-meditators matched on age, gender and education level, were scanned using structural Magnetic Resonance Imaging. Their GMV were extracted and compared using Voxel-Based Morphometry. Using a novel ad-hoc GLM model, statistical comparisons were made to observe if the GMV differences between meditators and controls were statistically significant.

Results

In the 16 lobe area subdivisions, GMV was statistically significantly different in 4 out of 16 areas: Right hemispheric temporal and frontal lobes, left frontal lobe and brainstem.

In the 116 AAL area subdivisions, GMV difference was statistically significant in 11 areas. The GMV differences were statistically more significant in right hemispheric brain areas.

Conclusions

The study shows that long-term practice of SYM is associated with larger GMV overall, and with significant differences mainly in temporal and frontal areas of the right hemisphere and the brainstem. These neuroplastic changes may reflect emotional and attentional control mechanisms developed with SYM. On the other hand, our statistical ad-hoc method shows that there were more brain areas with statistical significance compared to the traditional methodology which we think is susceptible to conservative Type II errors.
EUAdb: a resource for COVID-19 test development
Authors: Woronik Alyssa , Shaffer Henry W. , Kiontke Karin , Laurent Jon M. , Zambrano Ronald , Boeke Jef D. , Fitch David H. A.
Published: July 2020

Due to the sheer number of COVID-19 (coronavirus disease 2019) cases, the prevalence of asymptomatic cases and the fact that undocumented cases appear to be significant for transmission of the causal virus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), there is an urgent need for increased SARS-CoV-2 testing capability that is both efficient and effective1. In response to the growing threat of the COVID-19 pandemic in February, 2020, the FDA (US Food and Drug Administration) began issuing Emergency Use Authorizations (EUAs) to laboratories and commercial manufacturers for the development and implementation of diagnostic tests1. So far, the gold standard assay for SARS-CoV-2 detection is the RT-qPCR (real-time quantitative polymerase chain reaction) test2. However, the authorized RT-qPCR test protocols vary widely, not only in the reagents, controls, and instruments they use, but also in the SARS-CoV-2 genes they target, what results constitute a positive SARS-CoV-2 infection, and their limit of detection (LoD). The FDA has provided a web site that lists most of the tests that have been issued EUAs, along with links to the authorization letters and summary documents describing these tests1. However, it is very challenging to use this site to compare or replicate these tests for a variety of reasons. First, at least 12 of 18 tests for EUA submissions made prior to March 31, 2020, are not listed there. To our knowledge, no EUAs have been issued for these applications. Second, the data are not standardized and are only provided as longhand prose in the summary documents. Third, some details (e.g. primer sequences) are absent from several of the test descriptions. Fourth, for tests provided by commercial manufacturers, summary documents are completely missing. To address at least the first three issues, we have developed a database, EUAdb (EUAdb.org), that holds standardized information about EUA-issued tests and is focused on RT-qPCR diagnostic tests, or “high complexity molecular-based laboratory developed tests”1. By providing a standardized ontology and curated data in a relational architecture, we seek to facilitate comparability and reproducibility, with the ultimate goal of consistent, universal and high-quality testing nationwide. Here, we document the basics of the EUAdb data architecture and simple data queries. The source files can be provided to anyone who wants to modify the database for his/her own research purposes. We ask that the original source of the files be made clear and that the database not be used in its original or modified forms for commercial purposes.
Glycine Rich Segments Adopt Polyproline II Helices Which May Contribute to Biomolecular Condensate Formation
Authors: Mompeán Miguel , McAvan Bethan S. , Félix Sara S. , Treviño Miguel , Oroz Javier , Pantoja-Uceda David , Cabrita Eurico J. , Doig Andrew J. , Laurents Douglas V.
Published: July 2020

Many intrinsically disordered proteins contain Gly-rich regions which are generally assumed to be disordered. Such regions often form biomolecular condensates which play essential roles in organizing cellular processes. However, the bases of their formation and stability are still not completely understood. Considering NMR studies of the Gly-richH. harveyi“snow flea” antifreeze protein, we recently proposed that Gly-rich sequences, such as the third “RGG” region of Fused in Sarcoma (FUS) protein, may adopt polyproline II helices whose association might stabilize condensates. Here, this hypothesis is tested with a polypeptide corresponding to the third RGG region of FUS. NMR spectroscopy and molecular dynamics simulations suggest that significant populations of polyproline II helix are present. These findings are corroborated in a model peptide Ac-RGGYGGRGGWGGRGGY-NH2, where a peak characteristic of polyproline II helix is observed using CD spectroscopy. Its intensity suggests a polyproline II population of 40%. This result is supported by data from FTIR and NMR spectroscopies. In the latter, NOE correlations are observed between the Tyr and Arg, and Arg and Trp side chain hydrogens, confirming that side chains spaced three residues apart are close in space. Taken together, the data are consistent with a polyproline II helix, which is bent to optimize interactions between guanidinium and aromatic moieties, in equilibrium with a statistical coil ensemble. In cells, the polyproline II population of these peptides could be augmented by binding profilin protein or SH3, WW or OCRE domains, association with RNA or assembly into polyproline II helical bundles. These results lend credence to the hypothesis that Gly-rich segments of disordered proteins may form polyproline II helices which help stabilize biomolecular condensates.
Genetic signatures for lineage/sublineage classification of HPV16, 18, 52 and 58 variants
Authors: Ou Zhihua , Chen Zigui , Zhao Yanping , Lu Haorong , Liu Wei , Li Wangsheng , Geng Chunyu , Hu Guohai , Wang Xiaman , Ren Peidi , Liu Na , Zhu Shida , Lu Ling , Li Junhua
Published: July 2020

Increasing evidences indicate that high-risk HPV variants are heterogeneous in carcinogenicity and ethnic dispersion. In this work, we identified genetic signatures for convenient determination of lineage/sublineage of HPV16, 18, 52 and 58 variants. Using publicly available genomes, we found that E2 of HPV16, L2 of HPV18, L1 and LCR of HPV52, and L2, LCR and E1 of HPV58 contain the proper genetic signature for lineage/sublineage classification. Sets of hierarchical signature nucleotide positions (SNPs) were further confirmed for high accuracy (>98%) by classifying HPV genomes obtained from Chinese females, which included 117 HPV16 variants, 48 HPV18 variants 117 HPV52 variants and 89 HPV58 variants. The circulation of HPV variants posing higher cancer risk in Eastern China, such as HPV16 A4 and HPV58 A3, calls for continuous surveillance in this region. The marker genes and signature nucleotide positions may facilitate cost-effective diagnostic detections of HPV variants in clinical settings.
A dynamic regulatory interface on SARS-CoV-2 RNA polymerase
Authors: Shi Wei , Chen Ming , Yang Yang , Zhou Wei , Chen Shiyun , Yang Yi , Hu Yangbo , Liu Bin
Published: July 2020

The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is the core machinery responsible for the viral genome replication and transcription and also a major antiviral target. Here we report the cryo-electron microscopy structure of a post-translocated SARS-CoV-2 RdRp core complex, comprising one nsp12, one separate nsp8(I) monomer, one nsp7-nsp8(II) subcomplex and a replicating RNA substrate. Compared with the recently reported SARS-CoV-2 RdRp complexes, the nsp8(I)/nsp7 interface in this RdRp complex shifts away from the nsp12 polymerase. Further functional characterizations suggest that specific interactions between the nsp8(I) and nsp7, together with the rearrangement of nsp8(I)/nsp7 interface, ensure the efficient and processive RNA synthesis by the RdRp complex. Our findings provide a mechanistic insight into how nsp7 and nsp8 cofactors regulate the polymerase activity of nsp12 and suggest a potential new intervention interface, in addition to the canonical polymerase active center, in RdRp for antiviral design.

Author summary

Since it was first discovered and reported in late 2019, the coronavirus disease 2019 (COVID-19) pandemic caused by highly contagious SARS-CoV-2 virus is wreaking havoc around the world. Currently, no highly effective and specific antiviral drug is available for clinical treatment. Therefore, the threat of COVID-19 transmission necessitates the discovery of more effective antiviral strategies. Viral RNA-dependent RNA polymerase (RdRp) is an important antiviral drug target. Here, our cryo-EM structure of a SARS-CoV-2 RdRp/RNA replicating complex reveals a previously uncharacterized overall shift of the cofactor nsp8(I)/nsp7 interface, leading to its rearrangement. Throughin vitrofunctional test, we found that the specific interactions on the interface are important to the efficient RNA polymerase activity of SARS-CoV-2 RdRp. These observations let us to suggest this interface as a potential new drug intervention site, outside of the canonical polymerase active center, in RdRp for antiviral design. Our findings would provide new insights into regulatory mechanism of this novel SARS-CoV-2 RdRp, contribute to the design of antiviral drugs against SARS-CoV-2, and benefit the global public health.
Inference of population genetic parameters from the continuously serial-sampled sequences of human seasonal influenza A/H3N2
Authors: Croze Myriam , Kim Yuseob
Published: July 2020

Basic summary statistics that quantify the population genetic structure of influenza virus are important for understanding and inferring the evolutionary and epidemiological processes. However, global virus sequences were sampled continuously over several decades, scattered semi-randomly over time. This temporal structure of samples and the small effective size of viral population make it difficult to use conventional methods to calculate summary statistics. Here we define statistics that overcome this problem by correcting for sampling time difference in quantifying a pairwise sequence difference. A simple method of linear regression jointly estimates the mutation rate and the level of sequence polymorphism, thus providing the estimate of the effective population size. It also leads to the definition of Wright’sFSTfor arbitrary time-series data. In addition, as an alternative to Tajima’sDstatistic or site frequency spectrum, mismatch distribution corrected for sampling time differences can be obtained and compared between actual and simulated data. Application of these methods to seasonal influenza A/H3N2 viruses sampled between 1980 and 2017 and sequences simulated under the model of recurrent positive selection with meta-population dynamics allowed us to estimate the synonymous mutation rate and find parameter values of selection and demographic structure that fit the observation. We found that the mutation rates of HA and PB1 segments before 2007 were particularly high, and that adding recurrent positive selection in our model was essential for the genealogical structure of the HA segment. Methods developed here can be generally applied to population genetic inferences using serially sampled genetic data.
Heritability of individualized cortical network topography
Authors: Anderson Kevin M. , Ge Tian , Kong Ru , Patrick Lauren M. , Spreng R. Nathan , Sabuncu Mert R. , Thomas Yeo B.T. , Holmes Avram J.
Published: July 2020

Human cortex is patterned by a complex and interdigitated web of large-scale functional networks. Recent methodological breakthroughs reveal variation in the size, shape, and spatial topography of cortical networks across individuals. While spatial network organization emerges across development, is stable over time, and predictive of behavior, it is not yet clear to what extent genetic factors underlie inter-individual differences in network topography. Here, leveraging a novel non-linear multi-dimensional estimation of heritability, we provide evidence that individual variability in the size and topographic organization of cortical networks are under genetic control. Using twin and family data from the Human Connectome Project (n=1,023), we find increased variability and reduced heritability in the size of heteromodal association networks (h2: M=0.33, SD=0.071), relative to unimodal sensory/motor cortex (h2: M=0.44, SD=0.051). We then demonstrate that the spatial layout of cortical networks is influenced by genetics, using our multi-dimensional estimation of heritability (h2-multi; M=0.14, SD=0.015). However, topographic heritability did not differ between heteromodal and unimodal networks. Genetic factors had a regionally variable influence on brain organization, such that the heritability of network topography was greatest in prefrontal, precuneus, and posterior parietal cortex. Taken together, these data are consistent with relaxed genetic control of association cortices relative to primary sensory/motor regions, and have implications for understanding population-level variability in brain functioning, guiding both individualized prediction and the interpretation of analyses that integrate genetics and neuroimaging.

Significance

The widespread use of population-average cortical parcellations has provided important insights into broad properties of human brain organization. However, the size, location, and spatial arrangement of regions comprising functional brain networks can vary substantially across individuals. Here, we demonstrate considerable heritability in both the size and spatial organization of individual-specific network topography across cortex. Genetic factors had a regionally variable influence on brain organization, such that heritability in network size, but not topography, was greater in unimodal relative to heteromodal cortices. These data suggest individual-specific network parcellations may provide an avenue to understand the genetic basis of variation in human cognition and behavior.
Computational Properties of the Visual Microcircuit
Authors: Hahn Gerald , Kumar Arvind , Schmidt Helmut , Knösche Thomas R. , Deco Gustavo
Published: July 2020

The neocortex is organized around layered microcircuits consisting of a variety of excitatory and inhibitory neuronal types which perform rate-and oscillation based computations. Using modeling, we show that both superficial and deep layers of the primary mouse visual cortex implement two ultrasensitive and bistable switches built on mutual inhibitory connectivity motives between SST, PV and VIP cells. The switches toggle pyramidal neurons between high and low firing rate states that are synchronized across layers through translaminar connectivity. Moreover, inhibited and disinhibited states are characterized by low- and high frequency oscillations, respectively, with layer-specific differences in frequency and power which show asymmetric changes during state transitions. These findings are consistent with a number of experimental observations and embed firing rate together with oscillatory changes within a switch interpretation of the microcircuit.
Small-hairpin RNAs cause target-independent microRNA dysregulation in neurons and elicit global transcriptomic changes
Authors: Kohen Rafi , Baldwin Katherine T. , Garay Patricia M. , Tsukahara Takao , Chen Alex , Flynn Corey G. , Johnson Craig , Zhao Xiao-Feng , Sutton Michael A. , Iwase Shigeki , Giger Roman J.
Published: July 2020

Small hairpin RNAs (shRNAs) allow highly efficient gene knockdown. Here we employed different shRNAs to knock down the reticulon RTN4A/NogoA in primary neurons. Depletion of NogoA correlates with altered synaptic protein composition and spontaneous neurotransmission. However, similar phenotypes are not observed upon genetic deletion ofNogoor its receptors. Step-wise introduction of mismatches in the seed region of shNogoA provides further evidence that synaptic phenotypes are NogoA-independent. RNA sequencing revealed global changes in the neuronal transcriptome of cultures transduced with the original shNogoA or closely related variants. Transcriptomic changes are shRNA seed sequence dependent, but not target-specific. Parallel sequencing of small non-coding RNAs revealed dysregulation of microRNAs. Computational analysis shows that the altered miRNA composition correlates with changes in mRNA expression and preferentially affects protein-protein networks that function at synapses. Thus, off-target effects associated with shRNAs are an inherent property, and in particular, altered miRNA composition needs careful consideration.
singlecellVR: interactive visualization of single-cell data in virtual reality
Authors: Stein David F. , Chen Huidong , Vinyard Michael E. , Qin Qian , Combs Rebecca D. , Zhang Qian , Pinello Luca
Published: July 2020

Single-cell assays have transformed our ability to model heterogeneity within cell populations. As these assays have advanced in their ability to measure various aspects of molecular processes in cells, computational methods to analyze and meaningfully visualize such data have required matched innovation. Independently, Virtual Reality (VR) has recently emerged as a powerful technology to dynamically explore complex data and shows promise for adaptation to challenges in single-cell data visualization. However, adopting VR for single-cell data visualization has thus far been hindered by expensive prerequisite hardware or advanced data preprocessing skills. To address current shortcomings, we presentsinglecellVR, a user-friendly web application for visualizing single-cell data, designed for cheap and easily available virtual reality hardware (e.g., Google Cardboard, ∼$10).singlecellVRcan visualize data from a variety of sequencing-based technologies including transcriptomic, epigenomic, and proteomic data as well as combinations thereof. Analysis modalities supported include approaches to clustering as well as trajectory inference and visualization of dynamical changes discovered through modelling RNA velocity. We provide a companion software package,scvrto streamline data conversion from the most widely-adopted single-cell analysis tools as well as a growing database of pre-analyzed datasets to which users can contribute.
Common variants contribute to intrinsic human brain functional networks
Authors: Zhao Bingxin , Li Tengfei , Smith Stephen M. , Xiong Di , Wang Xifeng , Yang Yue , Luo Tianyou , Zhu Ziliang , Shan Yue , Matoba Nana , Sun Quan , Yang Yuchen , Hauberg Mads E. , Bendl Jaroslav , Fullard John F. , Roussos Panagiotis , Lin Weili , Li Yun , Stein Jason L. , Zhu Hongtu
Published: July 2020

The human brain remains active in the absence of explicit tasks and forms networks of correlated activity. Resting-state functional magnetic resonance imaging (rsfMRI) measures brain activity at rest, which has been linked with both cognitive and clinical outcomes. The genetic variants influencing human brain function are largely unknown. Here we utilized rsfMRI from 44,190 individuals of multiple ancestries (37,339 in the UK Biobank) to discover and validate the common genetic variants influencing intrinsic brain activity. We identified hundreds of novel genetic loci associated with intrinsic functional signatures (P< 2.8 × 10−11), including associations to the central executive, default mode, and salience networks involved in the triple network model of psychopathology. A number of intrinsic brain activity associated loci colocalized with brain disorder GWAS (e.g., Alzheimer’s disease, Parkinson’s disease, schizophrenia) and cognition, such as 19q13.32, 17q21.31, and 2p16.1. Particularly, we detected a colocalization between one (rs429358) of the two variants in theAPOEε4 locus and function of the default mode, central executive, attention, and visual networks. Genetic correlation analysis demonstrated shared genetic influences between brain function and brain structure in the same regions. We also detected significant genetic correlations with 26 other complex traits, such as ADHD, major depressive disorder, schizophrenia, intelligence, education, sleep, subjective well-being, and neuroticism. Common variants associated with intrinsic brain activity were enriched within regulatory element in brain tissues.
Complex modeling for the quantification of nanoscale disorder using genetic algorithms, density functional theory and line-profile analysis
Authors: Koch Robert J. , Li Guangfang , Pandey Shubham , Phillpot Simon R. , Wang Hui , Misture Scott T.
Published: July 2020

A new, computationally efficient, complex modeling approach is presented for the quantification of the local and average atomic structure, nanostructure and microstructure of an Au0.25Cu0.75alloy. High-resolution X-ray powder diffraction and whole pattern fitting show that the sample is phase pure, with isotropic lattice strain and a distribution of equiaxed crystallites of mean size 144 (11) nm, where each crystallite has on average four twin boundaries and an average of three deformation faults per four crystallites. Both small- and large-box model optimizations were used to extract local and long-range information from the pair distribution function. The large-box, 640 000-atom-ensemble optimization approach applied herein relies on differential evolution optimization and shows that the alloy has chemical short-range ordering, with correlation parameters of −0.26 (2) and 0.36 (8) in the first and second correlation shells, respectively. Locally, there is a 1.45 (8)% tetragonal distortion which on average results in a cubic atomic structure. The isotropic lattice strain is a result of atom-pair-dependent bond lengths, following the trenddAu—Au>dAu—Cu>dCu—Cu, highlighted by density functional theory calculations. This approach is generalizable and should be extensible to other disordered systems, allowing for quantification of localized structure deviations.
Career success in academia
Authors: Sherif Karma , Nan Ning , Brice Jeff
Published: July 2020

Purpose

In this study, the authors explore the boundaryless careers of faculty and adopt the intelligent career framework to examine success factors for academic careers.

Design/methodology/approach

The authors conducted a field study of 36 researchers in the management information systems field from 22 institutions in the US, Australia and Canada. The authors selected the participants representing four strata of researchers: luminaries (high expertise status and high citizenship behavior), experts (high expertise status but low leadership roles), statesmen (low expertise status but high leadership) and journeymen (low expertise status and low leadership). Data regarding the participants' experience of social relationships and social resources as well as entrepreneurial motivations were collected and analyzed.

Findings

Results show that faculty who “know-why”, “know-how”, and “know with whom” possess socially valued resources and are successful in advancing their careers. They establish high social status and exercise power within their networks to mobilize resources that promote their careers. On the other hand, faculty who fall short of these competencies impose social closure on themselves and do not strive to exploit resources available through their contacts. The study advances a number of theoretical propositions to guide future research on boundaryless intelligent careers.

Social implications

Social relationships and social resources do not substitute individual competence, leadership and entrepreneurial motivations; individuals need to develop competence valued by their professional communities and exploit available opportunities and assume leadership roles in order to effectively establish instrumental relationships and mobilize social resources to achieve career advancement.

Originality/value

In this study, we attempt to extend career development research through an examination of the bidirectional relationship between know-why, know-how and know-who in academia.
Forecasting key indicators of China's inbound and outbound tourism: optimistic–pessimistic method
Authors: Javed Saad Ahmed , Ikram Muhammad , Tao Liangyan , Liu Sifeng
Published: July 2020

Purpose

Tourism industry is a highly complex system surrounded by many uncertainties because of its innumerable connections with other supporting systems. Considering tourism, a grey system, the current study proposes optimistic–pessimistic method (OPM). This technique can aid in improving forecast accuracy of four tourism-related indicators, inbound tourism to China, outbound tourism from China, revenues collected through inbound tourism and expenses incurred on outbound tourism.

Design/methodology/approach

The study integrates OPM into EGM and then using the secondary data collected from the World Bank database, predicts the four tourism-related indicators. The mean absolute percentage error steered the performance of the models.

Findings

One of the main contributions of the study lies in its overall evaluation of one of the major travel and tourism countries of the world in light of four crucial indicators. The study highlights, four tourism-related indicators' recent information, contains more valuable information about the future.

Originality/value

OPM represents a novel application of concept of whitenization of interval grey number in grey forecasting theory.
Examining knowledge transfer activities in UK universities: advocating a PROMETHEE-based approach
Authors: Ishizaka Alessio , Pickernell David , Huang Shuangfa , Senyard Julienne Marie
Published: July 2020

Purpose

The purpose of this study is to examine the portfolio of knowledge transfer (KT) activities in 162 UK higher education institutions. In doing so, this study creates an index and ranking, but more importantly, it identifies specific groupings or strategic profiles of universities defined by different combinations and strengths of the individual KT activities from which the overall rankings are derived. Previous research, concentrating on entrepreneurial universities, shows that individual knowledge transfer (KT) activities vary substantially among UK universities. The broad portfolio of universities' KT activities, however, remains underexplored, creating gaps in terms of the relative strength, range, focus and combination of these activities, and the degree to which there are distinct university strategic KT profiles. By examining KT activities and grouping universities into KT “types”, this research allows universities and policymakers to better develop and measure clearer KT-strategies.

Design/methodology/approach

The present study applied the Preference Ranking Organization Method for the Enrichment of Evaluations (PROMETHEE) to rank universities based on their portfolio of KT activities. It utilised data from the 2015–2016 Higher Education Business and Community Interaction Survey dataset.

Findings

Findings show that universities differ substantially in their portfolios of KT activities. By using PROMETHEE, a new ranking of universities is generated, based on their KT portfolio. This paper also identifies four distinct types or groups of universities based on the diversity and intensity of their KT activities: Ambidextrous, broad, focused and indifferent.

Originality/value

The study contributes to the entrepreneurship literature, and more specifically entrepreneurial activities of universities through new knowledge generated concerning university KT activity. The research extends the existing literature on university archetypes (including those concerned with the Entrepreneurial University) and rankings using a new technique that allows for more detailed analysis of the range of university KT activities. By applying the PROMETHEE approach, results illustrate a more nuanced definition of university KT activities than before, by simultaneously evaluating their overall strength, range, focus and combination, allowing us to identify the universities' strategic profiles based on their KT portfolios. Implications of the findings for key stakeholders include a potential need for government higher education policymakers to take into account the different mixes of university archetypes in a region when considering how best to support higher education and its role in direct and indirect entrepreneurship promotion through regional policy goals.
Passion, performance and concordance in rock “n” roll entrepreneurship
Authors: Schulte-Holthaus Stefan , Kuckertz Andreas
Published: July 2020

Purpose

Non-entrepreneurial passions may be the beginning of an extensive entrepreneurial journey. However, current passion theories cannot fully capture the essence of such passions and their effects. The purpose of this study is to explore and explain the real-life composition of passion and performance.

Design/methodology/approach

The investigation was conducted with comparative causal mapping (CCM) on a qualitative sample of people we designate rock “n” roll entrepreneurs (i.e. individuals driven by a passion for music and who are successful both artistically and economically). Aggregated causal maps of passion elicited through semi-structured interviews were analyzed and contrasted with performance indicators.

Findings

Passion is revealed to be an individual phenomenon, one composed of central and peripheral concepts that include—contrary to prior theories—personality traits and life contexts. Furthermore, the results suggest that the concordance of concepts determines the scope, degree and performance of passion.

Research limitations/implications

This study complements prevailing passion theories in psychology and entrepreneurship. As a context-bound study, the generalizability of the results is limited to its context, which, however, paves a clear way for future research.

Practical implications

Creative economy entrepreneurs and educators can use the mechanism of concordance to consciously reflect passion-driven tensions between artistic, social and entrepreneurial demands and to translate passion into behavioral effectiveness.

Originality/value

This study is the first to use a CCM approach to investigate passion. Findings highlight the potential to research entrepreneurial phenomena at the intersection of emotion, cognition and action.
Impact of educational and gender inequality on income and income inequality in South Asian countries
Authors: Munir Kashif , Kanwal Ayesha
Published: July 2020

Purpose

The objectives of this study are threefold: firstly, to measure the impact of educational inequality on income inequality, and per capita income; secondly, to measure the impact of gender inequality in education on income inequality, per capita income and educational inequality; and lastly, to test the Kuznets inverted U-shape hypothesis between inequality in education and average year of schooling.

Design/methodology/approach

The study has adopted the Marin and Psacharopoulos (1976) model of human capital in which income earned by an individual can be estimated as a function of number of year spent in schooling or education. Gini coefficient is used as a measure of income inequality, while inequality in education is measured by Gini index of educational inequality. Gender inequality in education is measured by the difference between male and female enrolment ratios as a proportion of male enrolment. The study utilizes the data of six South Asian countries, i.e. Bangladesh, India, Maldives, Nepal, Pakistan and Sri Lanka from 1980 to 2010 at five-year average and employs fixed effect model (FEM) and random effect model (REM) for estimation.

Findings

Result suggests that educational inequality and average year of schooling have positive and significant impact on income inequality. Primary (basic) education and tertiary (higher) education reduce income inequality, while secondary education widens income inequality. Negative relationship exists between educational inequality and per capita income. Unequal distribution of education among boys and girls at primary level increases income inequality, while reduces income inequality at tertiary level. Gender inequality in secondary and tertiary level of education reduces per capita income, while unequal distribution of education among boys and girls further increases the educational inequality. Kuznets inverted U-shape hypothesis does not hold between education expansion and educational inequality, while weak U-shape relationship exists in South Asian countries.

Practical implications

Government has to provide free education in poor regions and makes employment programs to reduce the income and educational inequality respectively, while to remove gender inequality in education it is necessary to build more schools especially for girls. Government has to launch different online education programs for expansion in education at all levels.

Originality/value

This study adds to the literature by analyzing whether the inequality in income increases (decreases) due to increase (decrease) in educational and gender inequality in South Asian countries. This study contributes in the existing literature by developing a measure of educational and gender inequality in education in South Asian countries.

Peer review

The peer review history for this article is available at:https://publons.com/publon/10.1108/IJSE-04-2020-0226.
Fiscal management performance and local economic development: evidence from a large emerging economy
Authors: de Mendonça Helder Ferreira , Peçanha Matheus Souza
Published: July 2020

Purpose

This paper provides empirical evidence regarding the effect of fiscal management performance on local economic development in an emerging economy.

Design/methodology/approach

The authors performed a panel data analysis based on data from the 5,568 Brazilian municipalities from 2006 to 2015. To consider if the difference in the characteristics of the municipalities can affect the results, the authors used different samples: a total of municipalities, metropolitan, nonmetropolitan, urban and rural municipalities. Furthermore, to check the difference of the effect on economic development associated with good and bad fiscal management in the municipalities, the authors considered a sample of the 500 best and the 500 worst fiscal management performances.

Findings

The findings indicate that an improvement in fiscal management is an important strategy to stimulate local economic development. In particular, the relevance of fiscal management performance to stimulate economic development is more significant in metropolitan and urban municipalities.

Originality/value

This analysis is the first to use data that take into account all the Brazilian municipalities covering information of the 21st century. Moreover, different from the previous literature, which considered efficiency from the data envelopment analysis (DEA), the authors used a fiscal management index that allowed one to consider a time-varying fiscal performance of the Brazilian municipalities.
Can a case lead approach deliver the “craft and graft” of integration?
Authors: Bailey Di , Mutale Gabriella Jennifer
Published: July 2020

Purpose

The aim of this study was to explore the experiences and outcomes for adults with complex needs over time, within and between two teams that delivered integrated care across different Councils' services. The teams' approach to integration included two key features: a “case lead” way of working and the team itself operating as a single point of access (SPA) for residents in given neighbourhoods with high deprivation.

Design/methodology/approach

The study was designed as evaluation research located in the realist tradition. Two teams acted as a case study to provide an in-depth understanding of how the case lead approach and SPA delivered the craft and graft of integrated working in the teams. Mixed methods of data collection included residents' ratings of their quality of life on five domains in an outcome measure over a six-month period. Residents and staff working in the teams also participated in semi-structured interviews to explore their respective experiences and receiving and delivering integrated care. The costs of care delivery incurred by residents were calculated based on their demands on public services in the year leading up to the teams' intervention and the projected costs for one year following this.

Findings

The relationship between team context, case leads' inputs and residents' outcomes was mediated through the managerial style in the integrated teams which enabled case leads to be creative and do things differently with residents. Case leads worked holistically to prevent residents being in crisis as well as giving practical help such as sorting debts and finances and supporting access to volunteering or further education. Residents rated their quality of life as significantly improved over a six-month period and significant savings in costs as result of the teams' support were projected.

Originality/value

The study used a multi-evaluation realistic evaluation methodology to explore the relationship between team context, case leads' inputs and residents' outcomes in terms that integrated services across different District and County Council Departments.