bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversification, disparification, and hybridization in the desert shrubsEncelia
Authors: Singhal Sonal , Roddy Adam B. , DiVittorio Christopher , Sanchez-Amaya Ary , Henriquez Claudia L. , Brodersen Craig R. , Fehlberg Shannon , Zapata Felipe 
Published: August 2020

SummaryThere are multiple hypotheses for the spectacular plant diversity found in deserts. We explore how different factors, including the roles of ecological opportunity and selection, promote diversification and disparification inEncelia, a lineage of woody plants in the deserts of the Americas.Using a nearly complete species-level phylogeny along with a broad set of phenotypic traits, we estimate divergence times and diversification rates, identify instances of hybridization, quantify trait disparity, and assess phenotypic divergence across environmental gradients.We show thatEnceliaoriginated and diversified recently (mid-Pleistocene) and rapidly, with rates comparable to notable adaptive radiations in plants.Enceliaprobably originated in the hot deserts of North America, with subsequent diversification across steep environmental gradients. We uncover multiple instances of gene flow between species. The radiation ofEnceliais characterized by fast rates of phenotypic evolution, trait lability, and extreme disparity across environments and between species-pairs with overlapping geographic ranges.Enceliaexemplifies how interspecific gene flow in combination with high trait lability can enable exceptionally fast diversification and disparification across steep environmental gradients.
Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates
Authors: Patro L Ponoop Prasad , Sathyaseelan Chakkarai , Uttamrao Patil Pranita , Rathinavelan Thenmalarchelvi 
Published: August 2020

ABSTRACTTo accelerate the drug and vaccine development against the severe acute respiratory syndrome virus 2 (SARS-CoV-2), a comparative analysis of SARS-CoV-2 proteome has been performed in two phases by considering manually curated 31389 whole genome sequences from 84 countries. Among the 9 mutations that occur at a high significance (T85I-NPS2, L37F-NSP6, P323L-NSP12, D614G-spike, Q57H-ORF3a, G251V-ORF3a, L84S-ORF8, R203K-nucleocapsid and G204R-nucleocapsid), R203K-nucleocapsid and G204R-nucleocapsid are co-occurring (dependent) mutations and P323L-NSP12 and D614G-spike often appear simultaneously. Other notable variations that appear with a moderate to low significance are, M85-NSP1 deletion, D268-NSP2 deletion, 112 amino acids deletion in ORF8, a phenylalanine insertion amidst F34-F36 (NSP6) and several co-existing (dependent) substitution/deletion (I559V & P585S in NSP2, P504L & Y541C in NSP13, G82 & H83 deletions in NSP1 and K141, S142 & F143 deletions in NSP2) mutations. P323L-NSP12, D614G-spike, L37F-NSP6, L84S-ORF8 and the sequences deficient of the high significant mutations have led to 4 major SARS-CoV-2 clades. The top 5 countries bearing all the high significant and majority of the moderate significant mutations are: USA, England, Wales, Australia and Scotland. Further, the majority of the significant mutations have evolved in the first phase and have already transmitted around the globe indicating the positive selection pressure. Among the 26 SARS-CoV-2 proteins, nucleocapsid protein, ORF3a, ORF8, RNA dependent RNA polymerase and spike exhibit a higher heterogeneity compared with the rest of the proteins. However, NSP9, NSP10, NSP8, the envelope protein and NSP4 are highly resistant to mutations and can be exploited for drug/vaccine development.
Insecticide resistance status ofAedes aegyptiin Bangladesh
Authors: Al-Amin Hasan Mohammad , Johora Fatema Tuj , Irish Seth R. , Hossainey Muhammad Riadul Haque , Vizcaino Lucrecia , Paul Kishor Kumar , Khan Wasif A. , Haque Rashidul , Alam Mohammad Shafiul , Lenhart Audrey 
Published: August 2020

AbstractBackgroundArboviral diseases including dengue and chikungunya are major public health concern in Bangladesh, with unprecedented levels of transmission reported in recent years. The primary approach to control these diseases is control ofAedes aegyptiusing pyrethroid insecticides. Although chemical control is long-practiced, no comprehensive analysis ofAe. aegyptisusceptibility to insecticides has previously been conducted. This study aimed to determine the insecticide resistance status ofAe. aegyptiin Bangladesh and investigate the role of detoxification enzymes and altered target site sensitivity as resistance mechanisms.MethodsAedeseggs were collected using ovitraps from five districts across the country and in eight neighborhoods of the capital city Dhaka from August to November 2017. CDC bottle bioassays were conducted for permethrin, deltamethrin, malathion, and bendiocarb using 3-5-day old F0-F2non-blood fed female mosquitoes. Biochemical assays were conducted to detect metabolic resistance mechanisms and real-time PCR was performed to determine the frequencies of the knockdown resistance (kdr) mutations Gly1016, Cys1534, and Leu410.ResultsHigh levels of resistance to permethrin were detected in allAe. aegyptipopulations, with mortality ranging from 0 – 14.8% at the diagnostic dose. Substantial resistance continued to be detected against higher (2X) doses of permethrin (5.1 – 44.4% mortality). Susceptibility to deltamethrin and malathion varied between populations while complete susceptibility to bendiocarb was observed in all populations. Significantly higher levels of esterase and oxidase activity were detected in most of the test populations as compared to the susceptible reference Rockefeller strain. A significant association was detected between permethrin resistance and the presence of Gly1016 and Cys1534 homozygotes. The frequency ofkdralleles varied across the Dhaka populations, and Leu410 was not detected in any of the tested populations.ConclusionsThe detection of widespread pyrethroid resistance and multiple mechanisms highlights the urgency for implementing alternateAe. aegypticontrol strategies. In addition, implementing routine monitoring of insecticide resistance inAe. aegyptiin Bangladesh will lead to a greater understanding of susceptibility trends over space and time, thereby enabling the development of improved control strategies.
KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights into RAS-mediated RAF activation
Authors: Tran Timothy H. , Chan Albert H. , Young Lucy C. , Bindu Lakshman , Neale Chris , Messing Simon , Dharmaiah Srisathiyanarayanan , Taylor Troy , Denson John-Paul , Esposito Dominic , Nissley Dwight V. , Stephen Andrew G. , McCormick Frank , Simanshu Dhirendra K. 
Published: August 2020

ABSTRACTA vital first step of RAF activation involves binding to active RAS, resulting in the recruitment of RAF to the plasma membrane. To understand the molecular details of RAS-RAF interaction, we solved crystal structures of wild-type and oncogenic mutants of KRAS complexed with the RAS-binding domain (RBD) and the membrane-interacting cysteine-rich domain (CRD) from the N-terminal regulatory region of RAF1. Our structures revealed that RBD and CRD interact with each other to form one structural entity in which both RBD and CRD interact extensively with KRAS. Mutation at the KRAS-CRD interface resulted in a significant reduction in RAF1 activation despite only a modest decrease in binding affinity. Combining our structures and published data, we provide a model of RAS-RAF complexation at the membrane, and molecular insights into RAS-RAF interaction during the process of RAS-mediated RAF activation.
Force-dependent stimulation of RNA unwinding by SARS-CoV-2 nsp13 helicase
Authors: Mickolajczyk Keith J. , Shelton Patrick M.M. , Grasso Michael , Cao Xiaocong , Warrington Sara E. , Aher Amol , Liu Shixin , Kapoor Tarun M. 
Published: August 2020

ABSTRACTThe superfamily-1 helicase non-structural protein 13 (nsp13) is required for SARS-CoV-2 replication, making it an important antiviral therapeutic target. The mechanism and regulation of nsp13 has not been explored at the single-molecule level. Specifically, force-dependent unwinding experiments have yet to be performed for any coronavirus helicase. Here, using optical tweezers, we find that nsp13 unwinding frequency, processivity, and velocity increase substantially when a destabilizing force is applied to the dsRNA, suggesting a passive unwinding mechanism. These results, along with bulk assays, depict nsp13 as an intrinsically weak helicase that can be potently activated by picoNewton forces. Such force-dependent behavior contrasts the known behavior of other viral monomeric helicases, drawing stronger parallels to ring-shaped helicases. Our findings suggest that mechanoregulation, which may be provided by a directly bound RNA-dependent RNA polymerase, enables on-demand helicase activity on the relevant polynucleotide substrate during viral replication.
Synaptic inputs to the inferior olive from cerebellar and vestibular nuclei have distinct release kinetics and neurotransmitters
Authors: Turecek Josef , Regehr Wade G. 
Published: August 2020

AbstractThe inferior olive (IO) is comprised of electrically-coupled neurons that make climbing fiber synapses onto Purkinje cells. Neurons in different IO subnuclei are inhibited by synapses with wide ranging release kinetics. Inhibition can be exclusively synchronous, asynchronous, or a mixture of both. Whether the same boutons, neurons or sources provide these kinetically distinct types of inhibition was not known. We find that the deep cerebellar nuclei (DCN) and vestibular nuclei (VN) are two major sources of inhibition to the IO that are specialized to provide inhibitory input with distinct kinetics. DCN to IO synapses lack fast synaptotagmin isoforms, release neurotransmitter asynchronously, and are exclusively GABAergic. VN to IO synapses contain fast synaptotagmin isoforms, release neurotransmitter synchronously, and are mediated by combined GABAergic and glycinergic transmission. These findings indicate that VN and DCN inhibitory inputs to the IO are suited to control different aspects of IO activity.
Transcriptional Atlas of Ileal-Anal Pouch Immune Cells from Ulcerative Colitis Patients
Authors: Devlin Joseph C. , Axelrad Jordan , Hine Ashley M. , Chang Shannon , Sarkar Suparna , Lin Jian-Da , Ruggles Kelly V. , Hudesman David , Cadwell Ken , Loke P’ng 
Published: August 2020

ABSTRACTHow the human intestinal immune system is distinctly organized to respond to inflammation is still poorly understood. Here, we used single-cell RNA-sequencing to examine lamina propria CD45+ hematopoietic cells from patients with inflammatory bowel disease that have undergone ileal pouch-anal anastomosis, or the colon mucosa of ulcerative colitis patients. We identified a population ofIL1B+ antimicrobial macrophages andFOXP3/+BATF+ T cells that are associated and expanded in inflamed tissues, which we further validated in other scRNA-seq datasets from IBD patients. CD8+ T cells were unexpectedly more abundant in the pouch than colon. Cell type specific markers obtained from single-cell RNA-sequencing was used to infer representation from bulk RNA sequencing datasets, which further implicated antimicrobial macrophages expressingIL1BwithS100A8/A9calprotectin as being associated with inflammation, as well asBacteroidesandEscherichiabacterial species. Finally, we find that non-responsiveness to anti-integrin biologic therapies in UC patients is associated with the signature of this antimicrobial macrophage population in a subset of patients. This study identified conserved and distinct features of intestinal inflammation between parts of the small and large intestine undergoing similar inflammation conditions.
New Pathways of Mutational Change in SARS-CoV-2 Proteomes Involve Regions of Intrinsic Disorder Important for Virus Replication and Release
Authors: Tomaszewski Tre , DeVries Ryan S. , Dong Mengyi , Bhatia Gitanshu , Norsworthy Miles D. , Zheng Xuying , Caetano-Anolles Gustavo 
Published: August 2020

ABSTRACTThe massive worldwide spread of the SARS-CoV-2 virus is fueling the COVID-19 pandemic. Since the first whole-genome sequence was published in January 2020, a growing database of tens of thousands of viral genomes has been constructed. This offers opportunities to study pathways of molecular change in the expanding viral population that can help identify molecular culprits of virulence and virus spread. Here we investigate the genomic accumulation of mutations at various time points of the early pandemic to identify changes in mutationally highly active genomic regions that are occurring worldwide. We used the Wuhan NC_045512.2 sequence as a reference and sampled 15,342 indexed sequences from GISAID, translating them into proteins and grouping them by month of deposition. The per-position amino acid frequencies and Shannon entropies of the coding sequences were calculated for each month, and a map of intrinsic disorder regions and binding sites was generated. The analysis revealed dominant variants, most of which were located in loop regions and on the surface of the proteins. Mutation entropy decreased between March and April of 2020 after steady increases at several sites, including the D614G mutation site of the spike (S) protein that was previously found associated with higher case fatality rates and at sites of the NSP 12 polymerase and the NSP13 helicase proteins. Notable expanding mutations include R203K and G204R of the nucleocapsid (N) protein inter-domain linker region and G251V of the viroporin encoded by ORF3a between March and April. The regions spanning these mutations exhibited significant intrinsic disorder, which was enhanced and decreased by the N-protein and viroporin 3a protein mutations, respectively. These results predict an ongoing mutational shift from the spike and replication complex to other regions, especially to encoded molecules known to represent major β-interferon antagonists. The study provides valuable information for therapeutics and vaccine design, as well as insight into mutation tendencies that could facilitate preventive control.
An evolutionary perspective of DNA methylation patterns in skeletal tissues using a nonhuman primate model of osteoarthritis
Authors: Housman Genevieve , Quillen Ellen E. , Stone Anne C. 
Published: August 2020

AbstractObjectiveEpigenetic factors, such as DNA methylation, play an influential role in the development of the degenerative joint disease osteoarthritis (OA). These molecular mechanisms have been heavily studied in humans, and although OA affects several other animals in addition to humans, few efforts have taken an evolutionary perspective. This study explores the evolution of OA epigenetics by assessing the relationship between DNA methylation variation and knee OA development in baboons (Papio spp.) and by comparing these findings to human OA epigenetic associations.MethodsGenome-wide DNA methylation patterns were identified in bone and cartilage of the right distal femora from 56 pedigreed, adult baboons (28 with and 28 without knee OA) using the Illumina Infinium MethylationEPIC BeadChip.ResultsSeveral significantly differentially methylated positions (DMPs) and regions (DMRs) were found between tissue types. Substantial OA-related differential methylation was also identified in cartilage, but not in bone, suggesting that cartilage epigenetics may be more influential in OA than bone epigenetics. Additionally, some genes containing OA-related DMPs overlap with and display methylation patterns similar to those previously identified in human OA, revealing a mixture of evolutionarily conserved and divergent OA-related methylation patterns in primates.ConclusionsOverall, these findings reinforce current etiological perspectives of OA and enhance our evolutionary understanding of epigenetic mechanisms associated with OA. This work further establishes baboons as a valuable nonhuman primate model of OA, and continued investigations in baboons will help to disentangle the molecular mechanisms contributing to OA and their evolutionary histories.
The Naturalist's Journals of Gilbert White: exploring the roots of accounting for biodiversity and extinction accounting
Authors: Atkins Jill , Maroun Warren 
Published: August 2020

PurposeThis paper explores the historical roots of accounting for biodiversity and extinction accounting by analysing the 18th-century Naturalist's Journals of Gilbert White and interpreting them as biodiversity accounts produced by an interested party. The authors aim to contribute to the accounting history literature by extending the form of accounting studied to include nature diaries as well as by exploring historical ecological accounts, as well as contributing to the burgeoning literature on accounting for biodiversity and extinction accounting.Design/methodology/approachThe authors’ method involves analysing the content of Gilbert White's Naturalist's Journals by producing an 18th-century biodiversity account of species of flora and fauna and then interpretively drawing out themes from the Journals. The authors then provide a Whitean extinction account by comparing current species' status with White's biodiversity account from 250 years ago.FindingsThis paper uses Gilbert White's Naturalist's Journals as a basis for comparing biodiversity and natural capital 250 years ago with current species' status according to extinction threat and conservation status. Further the paper shows how early nature diary recording represents early (and probably the only) forms of accounting for biodiversity and extinction. The authors also highlight themes within White's accounts including social emancipation, problematisation, aesthetic elements and an example of an early audit of biodiversity accounting.Research limitations/implicationsThere are limitations to analysing Gilbert White's Naturalist's Journals given that the only available source is an edited version. The authors therefore interpret their data as accounts which are indicative of biodiversity and species abundance rather than an exactly accurate account.Practical implicationsFrom the authors’ analysis and reflections, the authors suggest that contemporary biodiversity accounting needs to incorporate a combination of narrative, data accounting and pictorial/aesthetic representation if it is to provide a rich and accurate report of biodiversity and nature. The authors also suggest that extinction accounting should draw on historical data in order to demonstrate change in natural capital over time.Social implicationsSocial implications include the understanding gleaned from the authors’ analysis of the role of Gilbert White as a nature diarist in society and the contribution made over time by his Journals and other writings to the development of nature accounting and recording, as well as to one’s understanding and knowledge of species of flora and fauna.Originality/valueTo the authors’ knowledge this is the first attempt to analyse and interpret nature diaries as accounts of biodiversity and extinction.
Deception by commission or by omission – management forecasts surrounding share repurchases
Authors: Chen Anthony , Lu Hung-Yuan (Richard) 
Published: August 2020

PurposeIn this study, the authors extend upon Brockmanet al.(2008), who provide evidence that managers opportunistically accelerate bad news prior to share repurchases, but provide limited evidence that managers withhold good news until after repurchases. The authors examine management forecasts surrounding share repurchases in periods when companies must disclose detailed repurchase information. The authors argue these disclosures increase managers' legal and reputation risks of accelerating bad news, but have a lesser effect on delaying good news.Design/methodology/approachFirst, the authors examine whether managers alter the information released to the market before buying back shares by comparing managerial forecasts made within 30 days before the beginning of a repurchasing period with those made outside of this window. Second, the authors examine whether managers are more likely to provide good news forecasts, in terms of both magnitude and frequency, after buying back shares. Lastly, the authors examine the impact of CEO stock ownership on managerial forecasting behavior surrounding share buybacks.FindingsConsistent with the authors’ hypotheses and contrary to Brockmanet al.(2008), the authors find limited evidence that the likelihood or magnitude of bad news forecasts is greater in the period before share buybacks. Instead, the authors document that the frequency and magnitude of good news forecasts increase in periods following share buybacks and that these associations are positively moderated by managerial equity incentives. The authors also find that the withholding of good news is associated with lower average repurchase prices and greater repurchase volume. The authors further show that, when litigation risk is greater, managers are less likely to accelerate bad news prior to repurchases and more likely to withhold good news until after. Overall, the study results are consistent with managers balancing the benefits of opportunistic repurchase behavior with the costs.Originality/valueThis study contributes to the management forecast and share repurchase literatures by providing evidence consistent with managers opportunistically releasing earnings forecasts in the period after buying back shares. Most importantly, the authors show that after the rule revision, managers refrain from actively disclosing bad news that carry higher legal costs. Instead, they opt for the omission of good news to repurchase stocks at lower prices. The study results reconcile the conflicting evidence of Brockmanet al.(2008) and Ge and Lennox (2011).
Industry 4.0 adoption key factors: an empirical study on manufacturing industry
Authors: Narula Sanjiv , Prakash Surya , Dwivedy Maheshwar , Talwar Vishal , Tiwari Surendra Prasad 
Published: August 2020

PurposeThis research aims to outline the key factors responsible for industry 4.0 (I4.0) application in industries and establish a factor stratification model.Design/methodology/approachThis article identifies the factor pool responsible for I4.0 from the extant literature. It aims to identify the set of key factors for the I4.0 application in the manufacturing industry and validate, classify factor pool using appropriate statistical tools, for example, factor analysis, principal component analysis and item analysis.FindingsThis study would shed light on critical factors and subfactors for implementing I4.0 in manufacturing industries from the factor pool. This study would shed light on critical factors and subfactors for implementing I4.0 in manufacturing industries. Strategy, leadership and culture are found key elements of transformation in the journey of I4.0. Additionally, design and development in the digital twin, virtual testing and simulations were also important factors to consider by manufacturing firms.Research limitations/implicationsThe proposed I4.0 factor stratification model will act as a starting point while designing strategy, adopting readiness index for I4.0 and creating a roadmap for I4.0 application in manufacturing. The I4.0 factors identified and validated in this paper will act as a guide for policymakers, researchers, academicians and practitioners working on the implementation of Industry 4.0. This work establishes a solid groundwork for developing an I4.0 maturity model for manufacturing industries.Originality/valueThe existing I4.0 literature is critically examined for creating a factor pool that further presented to experts to ensure sufficient rigor and comprehensiveness, particularly checking the relevance of subfactors for the manufacturing sector. This work is an attempt to identify and validate major I4.0 factors that can impact its mass adoption that is further empirically tested for factor stratification.