bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric evolvability leads to specialization without trade-offs
Authors: Draghi Jeremy A.
Published: September 2020

Many ideas about the evolution of specialization rely on trade-offs—an inability for one organism to express maximal performance in two or more environments. However, optimal foraging theory suggests that populations can evolve specialization on a superior resource without explicit trade-offs. Classical results in population genetics show that the process of adaptation can be biased toward further improvement in already productive environments, potentially widening the gap between superior and inferior resources. Here I synthesize these approaches with new insights on evolvability at low recombination rates, showing that emergent asymmetries in evolvability can push a population toward specialization in the absence of trade-offs. Simulations are used to demonstrate how adaptation to a more common environment interferes with adaptation to a less common but otherwise equal alternative environment. Shaped by recombination rates and other population-genetic parameters, this process results in either the retention of a generalist niche without trade-offs or entrapment at the local optimum of specialization on the common environment. These modeling results predict that transient differences in evolvability across traits during an episode of adaptation could have long-term consequences for a population’s niche.
Clostridioides difficilespore-entry into intestinal epithelial cells contributes to recurrence of the disease
Authors: Castro-Córdova Pablo , Mora-Uribe Paola , Reyes-Ramírez Rodrigo , Cofré-Araneda Glenda , Orozco-Aguilar Josué , Brito-Silva Christian , Mendoza-León María José , Kuehne Sarah A. , Minton Nigel P. , Pizarro-Guajardo Marjorie , Paredes-Sabja Daniel
Published: September 2020

Clostridioides difficilespores produced during infection are essential for the recurrence of the disease. However, howC. difficilespores persist in the intestinal mucosa to cause recurrent infection remains unknown. Here, we show thatC. difficilespores gain entry into the intestinal mucosa via fibronectin-α5β1and vitronectin-αvβ1specific-pathways. The spore-surface exosporium BclA3 protein is essential for both spore-entry pathways into intestinal epithelial cells. Furthermore,C. difficilespores of abclA3isogenic mutant exhibited reduced entry into the intestinal mucosa and reduced recurrence of the disease in a mouse model of the disease. Inhibition ofC. difficilespore-entry led to reduced spore-entry into the intestinal epithelial barrier and recurrence ofC. difficileinfectionin vivo. These findings suggest thatC. difficilespore-entry into the intestinal barrier is a novel mechanism of spore-persistence that can contribute to infection recurrence and have implications for the rational design of therapies.
A non-canonical EZH2 function sensitizes solid tumors to genotoxic stress
Authors: Liao Yiji , Chen Chen-Hao , Shah Neel , Xiao Tengfei , Feit Avery , Yang Mei , Cai Changmeng , Gao Shuai , Xue Pengya , Liu Zhijie , Xu Han , Lee Jihoon , Li Wei , Mei Shenglin , Pierre Roodolph S. , Shu Shaokun , Fei Teng , Duarte Melissa , Zhao Jin , Bradner James E. , Polyak Kornelia , Kantoff Philip W. , Long Henry , Balk Steven P. , Liu X. Shirley , Brown Myles , Xu Kexin
Published: September 2020

Drugs that block the activity of the methyltransferase EZH2 are in clinical development for the treatment of non-Hodgkin lymphomas harboring gain-of-function EZH2 mutations that enhance its polycomb repressive function. In contrast, in castration-resistant prostate cancer (CRPC) we have previously reported that EZH2 plays a non-canonical role as a transcriptional activator. In this setting, we now show that EZH2 inhibitors can also block the non-canonical activity of EZH2 and inhibit the growth of CRPC cells. Gene expression and epigenomic profiling of cells treated with EZH2 inhibitors demonstrated that rather than de-repressing tumor suppressor genes silenced by PRC2, EZH2 inhibitors downregulate a set of DNA repair genes that are directly regulated by EZH2. In addition, genome-wide CRISPR/Cas9-mediated loss-of-function screens in the presence of EZH2 inhibitors identified these DNA repair genes to underlie the growth-inhibitory function of these compounds. Interrogation of public data from diverse solid tumor types expressing wild-type EZH2 showed that expression of DNA damage repair genes is significantly correlated with cellular sensitivity to EZH2 inhibitors. Consistent with these findings, treatment of CRPC cells with EZH2 inhibitors dramatically enhanced their sensitivity to genotoxic stress. These studies reveal a previously unappreciated mechanism of action of EZH2 inhibitors and provide a mechanistic basis for potential new combination cancer therapies.
Unique and distinct identities and functions of leaf phloem cells revealed by single cell transcriptomics
Authors: Kim Ji-Yun , Symeonidi Efthymia , Pang Tin Yau , Denyer Tom , Weidauer Diana , Bezrutczyk Margaret , Miras Manuel , Zöllner Nora , Wudick Michael M. , Lercher Martin , Chen Li-Qing , Timmermans Marja C.P , Frommer Wolf B.
Published: September 2020

Abstract

The leaf vasculature plays a key role in solute translocation. Veins consist of at least seven distinct cell types, with specific roles in transport, metabolism, and signaling. Little is known about the vascular cells in leaves, in particular the phloem parenchyma (PP). PP effluxes sucrose into the apoplasm as a basis for phloem loading; yet PP has only been characterized microscopically. Here, we enriched vascular cells from Arabidopsis leaves to generate a single-cell transcriptome atlas of leaf vasculature. We identified ≥19 cell clusters, encompassing epidermis, guard cells, hydathodes, mesophyll, and all vascular cell types, and used metabolic pathway analysis to define their roles. Clusters comprising PP cells were enriched for transporters, includingSWEET11andSWEET12sucrose and UmamiT amino acid efflux carriers. PP development occurs independently from APL, a transcription factor required for phloem differentiation. PP cells have a unique pattern of amino acid metabolism activity distinct from companion cells (CC), explaining differential distribution/metabolism of amino acids in veins. The kinship relation of the vascular clusters is strikingly similar to the vein morphology, except for a clear separation of CC from the other vascular cells including PP. In summary, our scRNA-seq analysis provides a wide range of information into the leaf vasculature and the role and relationship of the leaf cell types.
Assessing the relationship between cognitive empathy, age, and face perception using a sequential Bayesian analysis
Authors: Kist J.D. , Bethlehem R.A.I. , Stonier Barnaby , Sluijters Olivier , Crockford S. K. , de Jonge Elke , Freyberg Jan , Baron-Cohen Simon , Parsons O. E.
Published: September 2020

The ability to correctly identify emotions in social stimuli such as faces is proposed to affect one’s level of cognitive empathy. The Fusiform Face Area shows a heightened neural response during the perception of faces relative to objects. We tested whether neural responses to social stimuli were associated with performance in a measure of cognitive empathy, the ‘Reading the Mind in the Eyes’ Task. To quantify face perception, participants were presented with images during a fast serial presentation task which elicited a steady state visual evoked potential, measured using electroencephalography. A Sequential Bayesian Analysis was used to assess if face specific neural responses were associated with either cognitive empathy or age. Data were collected from a participant group of both neurotypical individuals and individuals on the autistic spectrum. We found no significant relationship between the face-specific neural signature, cognitive empathy or age. This study highlights the efficiency of the Sequential Bayesian Analysis as an effective method of participant recruitment.
An extended catalogue of tandem alternative splice sites in human tissue transcriptomes
Authors: Mironov Aleksei , Denisov Stepan , Gress Alexander , Kalinina Olga V. , Pervouchine Dmitri D.
Published: September 2020

Tandem alternative splice sites (TASS) is a special class of alternative splicing events that are characterized by a close tandem arrangement of splice sites. Most TASS lack functional characterization and are believed to arise from splicing noise. Based on the RNA-seq data from the Genotype Tissue Expression project, we present an extended catalogue of TASS in healthy human tissues and analyze their tissue-specific expression. The expression of TASS is usually dominated by one major splice site (maSS), while the expression of minor splice sites (miSS) is at least an order of magnitude lower. Among 73k miSS with sufficient read support, 12k (17%) are significantly expressed above the expected noise level, and among them 2k are expressed tissue-specifically. We found significant correlations between tissue-specific expression of RNA-binding proteins (RBP) and tissue-specific expression of miSS that is consistent with miSS response to RBP inactivation by shRNA. In combination with RBP profiling by eCLIP, this allowed prediction of novel cases of tissue-specific splicing regulation including a miSS in QKI mRNA that is likely regulated by PTBP1. According to the structural annotation of the human proteome, tissue-specific miSS are enriched within disordered regions, and indels induced by miSS are enriched with short linear motifs and post-translational modification sites. Nonetheless, more than 15% of tissue-specific miSS affect structured protein regions and may adjust protein-protein interactions or modify the stability of the protein core. The significantly expressed miSS evolve under the same selection pressure as maSS, while other miSS lack signatures of evolutionary selection and conservation. Using mixture models, we estimated that not more than 10% of maSS and not more than 50% of significantly expressed miSS are noisy, while the proportion of noisy splice sites among not significantly expressed miSS is above 70%.
Microbiome-based environmental monitoring of a dairy processing facility highlights the challenges associated with low microbial-load samples
Authors: McHugh Aoife J. , Yap Min , Crispie Fiona , Feehily Conor , Hill Colin , Cotter Paul D.
Published: September 2020

Food processing environments can harbor microorganisms responsible for food spoilage or foodborne disease. Efficient and accurate identification of microorganisms throughout the food chain can allow the identification of sources of contamination and the timely implementation of control measures. Currently, microbial monitoring of the food chain relies heavily on culture-based techniques. These assays are determined on the microbes expected to be present in the environment, and thus do not cater for unexpected contaminants. Many culture-based assays are also unable to distinguish between undesirable taxa and closely related harmless species. Furthermore, even when multiple culture-based approaches are used in parallel, it is still not possible to comprehensively characterize the entire microbiology of a food-chain sample.

High throughput DNA sequencing represents a potential means through which microbial monitoring of the food chain can be enhanced. While sequencing platforms, such as the Illumina MiSeq, NextSeq and NovaSeq, are most typically found in research or commercial sequencing laboratories, newer portable platforms, such as the Oxford Nanopore Technologies (ONT) MinION, offer the potential for rapid analysis of food chain microbiomes. In this study, having initially assessed the ability of rapid MinION-based sequencing to discriminate between different microbes within a simple mock metagenomic mixture of related food spoilage, spore-forming microorganisms. Subsequently, we proceeded to compare the performance of both ONT and Illumina sequencing for environmental monitoring of an active food processing facility.

Overall, ONT MinION sequencing provided accurate classification to species level, which was comparable to Illumina-derived outputs. However, while the MinION-based approach provided a means of easy library preparations and portability, the high concentrations of DNA needed to run the rapid sequencing protocols was a limiting factor, requiring the random amplification of template DNA in order to generate sufficient material for analysis.
Human IFITM3 restricts Chikungunya virus and Mayaro virus infection and is susceptible to virus-mediated counteraction
Authors: Franz Sergej , Zillinger Thomas , Pott Fabian , Schüler Christiane , Dapa Sandra , Fischer Carlo , Passos Vânia , Stenzel Saskia , Chen Fangfang , Döhner Katinka , Hartmann Gunther , Sodeik Beate , Pessler Frank , Simmons Graham , Drexler Jan Felix , Goffinet Christine
Published: September 2020

Interferon-induced transmembrane (IFITM) proteins restrict infection by enveloped viruses through interfering with membrane fusion and virion internalisation. The role of IFITM proteins during alphaviral infection of human cells and viral counteraction strategies remain largely unexplored. Here, we characterized the impact of IFITM proteins and variants on entry and spread of Chikungunya virus (CHIKV) and Mayaro virus (MAYV) in human cells, and provide first evidence for a CHIKV-mediated antagonism of IFITM proteins. IFITM1, 2 and 3 restricted infection at the level of alphavirus glycoprotein-mediated entry, both in the context of direct infection and during cell-to-cell transmission. Relocalization of normally endosomal IFITM3 to the plasma membrane resulted in the loss of its antiviral activity. rs12252-C, a naturally occurring variant ofIFITM3that has been proposed to associate with severe influenza in humans, restricted CHIKV, MAYV and influenza A virus infection as efficiently as wild-typeIFITM3. Finally, all antivirally active IFITM variants displayed reduced cell surface levels in CHIKV-infected cells involving a posttranscriptional process mediated by one or several non-structural protein(s) of CHIKV.
Detection of sexually antagonistic transmission distortions in trio datasets
Authors: Lucotte Elise A. , Albiñana Clara , Laurent Romain , Bhérer Claude ,   Genome of the Netherland Consortium, Bataillon Thomas , Toupance Bruno
Published: September 2020

Sex dimorphisms are widespread in animals and plants, for morphological as well as physiological traits. Understanding the genetic basis of sex dimorphism and its evolution is crucial for understanding biological differences between the sexes. Genetic variants with sex-antagonistic effects on fitness are expected to segregate in populations at the early phases of sexual dimorphism emergence. Detecting such variants is notoriously difficult, and the few genome-scan methods employed so far have limited power and little specificity. Here, we propose a new framework to detect a signature of sexually antagonistic selection. We rely on trio datasets where sex-biased transmission distortions can be directly tracked from parents to offspring, and allows identifying signal of sexually antagonistic transmission distortions in genomic regions. We report the genomic location and recombination pattern surrounding 66 regions detected as potentially under sexually antagonist selection. We find an enrichment of genes associated with embryonic development within these regions. Last, we highlight two candidates regions for sexually antagonistic selection in humans.
Acquisition of Host Cytosolic Protein byToxoplasma gondiiBradyzoites
Authors: Kannan Geetha , Thaprawat Pariyamon , Schultz Tracey L. , Carruthers Vern B.
Published: September 2020

Toxoplasma gondiiis a protozoan parasite that persists in the central nervous system as intracellular chronic stage bradyzoites that are encapsulated by a thick cyst wall. While the cyst wall separates bradyzoites from the host cytosol, it has been posited that small solutes can traverse the cyst wall to sustain bradyzoites. Recently it was found that host cytosolic macromolecules can cross the parasitophorous vacuole and are ingested and digested by actively replicating acute stage tachyzoites. However, the extent to which bradyzoites have an active ingestion pathway remained unknown. To interrogate this, we modified previously published protocols that look at tachyzoite acquisition and digestion of host proteins by measuring parasite accumulation of a host-expressed reporter protein after impairment of an endolysosomal protease (Cathepsin Protease L, CPL). Using two cystogenic parasite strains (ME49 and Pru), we demonstrate thatT. gondiibradyzoites can ingest host-derived cytosolic mCherry. Bradyzoites acquire host mCherry within 4 hours of invasion and post-cyst wall formation. This study provides direct evidence that host macromolecules can be internalized byT. gondiibradyzoites across the cyst wall in infected cells.
Refinement of a Cryo-EM Structure of hERG: Bridging Structure and Function
Authors: Khan H.M. , Guo J. , Duff H.J. , Tieleman D. P. , Noskov S. Y.
Published: September 2020

The humanether-a-go-go-related gene (hERG) encodes the voltage gated potassium channel (KCNH2 or Kv11.1, commonly known as hERG). This channel plays a pivotal role in the stability of phase 3 repolarization of the cardiac action potential. Although a high-resolution cryo-EM structure is available for its depolarized (open) state, the structure surprisingly did not feature many functionally important interactions established by previous biochemical and electrophysiology experiments. Using Molecular Dynamics Flexible Fitting (MDFF), we refined the structure and recovered the missing functionally relevant salt bridges in hERG in its depolarized state. We also performed electrophysiology experiments to confirm the functional relevance of a novel salt bridge predicted by our refinement protocol. Our work shows how refinement of a high-resolution cryo-EM structure helps to bridge the existing gap between the structure and function in the voltage-sensing domain (VSD) of hERG.

Statement of Significance

Cryo-EM has emerged as a major breakthrough technique in structural biology of membrane proteins. However, even high-resolution Cryo-EM structures contain poor side chain conformations and interatomic clashes. A high-resolution cryo-EM structure of hERG1 has been solved in the depolarized (open) state. The state captured by Cryo-EM surprisingly did not feature many functionally important interactions established by previous experiments. Molecular Dynamics Flexible Fitting (MDFF) used to enable refinement of the hERG1 channel structure in complex membrane environment re-establishing key functional interactions in the voltage sensing domain.
Effects of underlying gene-regulation network structure on prediction accuracy in high-dimensional regression
Authors: Okinaga Yuichi , Kyogoku Daisuke , Kondo Satoshi , Nagano Atsushi J. , Hirose Kei
Published: September 2020

Motivation

The least absolute shrinkage and selection operator (lasso) and principal component regression (PCR) are popular methods of estimating traits from high-dimensional omics data, such as transcriptomes. The prediction accuracy of these estimation methods is highly dependent on the covariance structure, which is characterized by gene regulation networks. However, the manner in which the structure of a gene regulation network together with the sample size affects prediction accuracy has not yet been sufficiently investigated. In this study, Monte Carlo simulations are conducted to investigate the prediction accuracy for several network structures under various sample sizes.

Results

When the gene regulation network was random graph, the simulation indicated that models with high estimation accuracy could be achieved with small sample sizes. However, a real gene regulation network is likely to exhibit a scale-free structure. In such cases, the simulation indicated that a relatively large number of observations is required to accurately predict traits from a transcriptome.

Availability and implementation

Source code athttps://github.com/keihirose/simrnet

Contact

hirose@imi.kyushu-u.ac.jp
Mild reductions in guard cellsucrose synthase2 expression leads to slower stomatal opening and decreased whole plant transpiration in tobacco
Authors: Freire Francisco Bruno S. , Bastos Ricardo L. G. , Bret Raissa S. C. , Cândido-Sobrinho Silvio A. , Medeiros David B. , Antunes Werner C. , Fernie Alisdair R. , Daloso Danilo M.
Published: September 2020

The understanding of the dynamics of stomatal movements has increased substantially through genetic manipulation of plant metabolism either at the whole plant level or specifically in guard cells. However, the regulation of stomatal speediness remains not completely elucidated. Here we shown that reduced expression of guard cell sucrose synthase 2(NtSUS2) ofNicotiana tabacumL. altered the topology and the connectivity of the guard cell metabolic network and the accumulation of metabolites positively correlated with stomatal speediness during dark-to-light transition. This leads to a slower light-induced stomatal opening, lower steady-state stomatal conductance and a strong reduction (up to 44%) in daily whole plant transpiration in the transgenics, when compared to wild type plants. Furthermore, the transgenic lines transpired more or have lower reduction in whole plant transpiration under short water deficit periods, indicating a higher effective use of water under this condition. Our results collectively suggest that the regulation of stomatal movement and speediness involve a complex modulation of the guard cell metabolic network, in whichNtSUS2has an important role. The results are discussed on the role of guard cell metabolism for the regulation of both stomatal speediness and whole plant transpiration.
Cevipabulin-tubulin complex reveals a novel agent binding site on α-tubulin with tubulin degradation effect
Authors: Yang Jianhong , Yu Yamei , Li Yong , Yan Wei , Ye Haoyu , Niu Lu , Tang Minghai , Wang Zhoufeng , Yang Zhuang , Pei Heying , Wei Haoche , Zhao Min , Wen Jiaolin , Yang Linyu , Ouyang Liang , Wei Yuquan , Chen Qiang , Li Weimin , Chen Lijuan
Published: September 2020

Microtubule, composed of αβ-tubulin heterodimers, remains as one of the most popular anticancer targets for decades. To date, anti-microtubule drugs are mainly functionally divided into microtubule-destabilizing and microtubule-stabilizing agents while microtubule- or tubulin-degradation agents are rarely reported. Six known binding sites on tubulin dimer are identified with five sites on β-tubulin and only one site on α-tubulin (pironetin site), hinting compounds binding to α-tubulin are less well characterized. Cevipabulin, a microtubule-active antitumor clinical candidate, is widely accepted as a microtubule-stabilizing agent by binding to the vinblastine site. Our X-ray crystallography study reveals that, in addition binding to the vinblastine site, cevipabulin also binds to a novel site on α-tubulin (named the seventh site) which located near the nonexchangeable GTP. Interestingly, we find the binding of cevipabulin to the seventh site induces tubulin degradation. As the non-exchangeable GTP has structural role and is important for the stability of tubulin dimers, we propose and confirm the tubulin degradation mechanism as: Cevipabulin at the seventh site puts the αT5 loop outward to make the non-exchangeable GTP exchangeable, which reduces the stability of tubulin and results in its destabilization and degradation. Our results confirm a novel agent binding site on α-tubulin and shed light on the development of tubulin degraders as a new generation of anti-microtubule drugs targeting this novel site.
Selfish chromosomal drive shapes recent centromeric histone evolution in monkeyflowers
Authors: Finseth Findley R. , Nelson Thom C. , Fishman Lila
Published: September 2020

Under the selfish centromere model, costs associated with female meiotic drive by centromeres select on interacting kinetochore proteins to restore Mendelian inheritance. We directly test this model in yellow monkeyflowers (Mimulus guttatus), which are polymorphic for a costly driving centromere (D). We show that theDhaplotype is structurally and genetically distinct and swept to a high stable frequency within the past 1500 years. Quantitative genetic analyses reveal that variation in the strength of drive primarily depends on the identity of the non-Dcentromere, but also identified an unlinked modifier coincident with kinetochore protein Centromere-specific Histone 3 A (CenH3A). CenH3A has also experienced a recent (<1000 years) selective sweep in our focal population, consistent with ongoing interactions withDshaping its evolution. Together, our results demonstrate an active co-evolutionary arms race between the DNA and protein components of the meiotic machinery, with important consequences for individual fitness and molecular divergence.
Kinetic-Mechanistic Evidence for WhichE. coliRNA Polymerase-λPROpen Promoter Complex Initiates and for Stepwise Disruption of Contacts in Bubble Collapse
Authors: Plaskon Dylan , Henderson Kate , Felth Lindsey , Molzahn Cristen , Evensen Claire , Dyke Sarah , Shkel Irina , Record M. Thomas
Published: September 2020

In transcription initiation, specific contacts between RNA polymerase (RNAP) and promoter DNA are disrupted as the RNA-DNA hybrid advances into the cleft, resulting in escape of RNAP. From the pattern of large and small rate constants for steps of initiation at λPRpromoter at 19°C, we proposed that in-cleft interactions are disrupted in extending 3-mer to 5-mer RNA, −10 interactions are disrupted in extending 6-mer to 9-mer, and −35 interactions are disrupted in extending 10-mer to 11-mer, allowing RNAP to escape. Here we test this mechanism and determine enthalpic and entropic activation barriers of all steps from kinetic measurements at 25°C and 37°C. Initiation at 37°C differs significantly from expectations based on lower-temperature results. At low concentration of the second iNTP (UTP), synthesis of full-length RNA at 37°C is slower than at 25°C and no transient short RNA intermediates are observed, indicating a UTP-dependent bottleneck step early in the 37°C mechanism. Analysis reveals that the 37°C λPROC (RPO) cannot initiate and must change conformation to a less-stable initiation complex (IC) capable of binding the iNTP. We find that IC is the primary λPROC species below 25°C, and therefore conclude that IC must be the I3intermediate in RPOformation. Surprisingly, Arrhenius activation energy barriers to five steps where RNAP-promoter in-cleft and −10 contacts are disrupted are much smaller than for other steps, including a negative barrier for the last of these steps. We interpret these striking effects as enthalpically-favorable, entropically-unfavorable, stepwise bubble collapse accompanying disruption of RNAP contacts.

Significance

Transcription initiation is highly regulated. To understand regulation, mechanisms of initiation and escape of RNA polymerase (RNAP) from the promoter must be understood. RNAP forms a highly-stable open complex (RPO) with λPRpromoter at 37°C. From experiments determining effects of temperature on rate constants for each step of RNA synthesis, we find that RPOcannot bind the initiating nucleotides, that the I3intermediate and not RPOis the initiation complex, and that contacts of RNAP with single-stranded DNA of the discriminator and −10 region and with −35 duplex DNA are disrupted stepwise as the RNA-DNA hybrid moves into the cleft. Evidence is obtained for stepwise bubble collapse and base stacking accompanying disruption of interactions of the single-stranded discriminator and −10 regions with RNAP.
Control of feeding by Piezo-mediated gut mechanosensation inDrosophila
Authors: Min Soohong , Oh Yangkyun , Verma Pushpa , Van Vactor David , Suh Greg S.B. , Liberles Stephen D.
Published: September 2020

Across animal species, meals are terminated after ingestion of large food volumes, yet underlying mechanosensory receptors have so far remained elusive. Here, we identify an essential role forDrosophilaPiezo in volume-based control of meal size. We discover a rare population of fly neurons that express Piezo, innervate the anterior gut and crop (a food reservoir organ), and respond to tissue distension in a Piezo-dependent manner. Activating Piezo neurons decreases appetite, whilePiezoknockout and Piezo neuron silencing cause gut bloating and increase both food consumption and body weight. These studies reveal that disrupting gut distension receptors changes feeding patterns, and identify a key role forDrosophilaPiezo in internal organ mechanosensation.
Co-targeting myelin inhibitors and CSPGs markedly enhances regeneration of GDNF-stimulated, but not conditioning-lesioned, sensory axons into the spinal cord
Authors: Zhai Jinbin , Kim Hyukmin , Han Seung Baek , Manire Meredith , Yoo Rachel , Pang Shuhuan , Smith George M. , Son Young-Jin
Published: September 2020

A major barrier to intraspinal regeneration after dorsal root (DR) injury is the DR entry zone (DREZ), the CNS/PNS interface. DR axons stop regenerating at the DREZ, even if regenerative capacity is increased by a nerve conditioning lesion. This potent blockade has long been attributed to myelin-associated inhibitors and CSPGs, but incomplete lesions and conflicting reports have prevented conclusive agreement. Here we evaluated DR regeneration in mice, using novel strategies to facilitate complete lesions and analyses, selective tracing of proprioceptive and mechanoreceptive axons, and the first simultaneous targeting of Nogo/Reticulon-4, MAG, OMgp, CSPGs and GDNF. Co-eliminating myelin inhibitors and CSPGs elicited regeneration of only a few conditioning-lesioned DR axons across the DREZ. Their absence, however, markedly and synergistically enhanced regeneration of GDNF-stimulated axons, highlighting the importance of sufficiently elevating intrinsic growth capacity. We also conclude that myelin inhibitors and CSPGs are not the primary mechanism stopping axons at the DREZ.
SOX9 acts as a dynamic pioneer factor inducing stable changes in the chromatin landscape to reprogram endothelial cells
Authors: Fuglerud Bettina M. , Drissler Sibyl , Lotto Jeremy , Stephan Tabea L. , Thakur Avinash , Cullum Rebecca , Hoodless Pamela A.
Published: September 2020

The transcription factor SOX9 is expressed in multiple tissues during embryogenesis and directs developmental processes. SOX9 is activated upon endothelial-to-mesenchymal transition (EndMT) in the developing heart, but its role in regulating this process is less clear. Using human umbilical vein endothelial cells as an EndMT model, we show that SOX9 expression alone is sufficient to activate mesenchymal enhancers and steer endothelial cells towards a mesenchymal fate. By genome-wide mapping of the chromatin landscape, we show that SOX9 acts as a pioneer transcription factor, having the ability to open chromatin and lead to deposition of active histone marks at a specific subset of previously silent enhancers, guided by SOX motifs and H2A.Z enrichment. This leads to a switch in enhancer activity states resulting in activation of mesenchymal genes and concurrent suppression of endothelial genes to drive EndMT. Moreover, we show that SOX9 chromatin binding is dynamic, but induces stable changes in the chromatin landscape. Our data also show widespread SOX9 chromatin scanning in silent chromatin that is not associated with SOX motifs or H2A.Z enrichment. Our study highlights the crucial developmental role of SOX9 and provides new insight into key molecular functions of SOX9 in the chromatin landscape and mechanisms of EndMT.

Graphical abstract
Treatment of the X chromosome in mapping multiple quantitative trait loci
Authors: Tran Quoc , Broman Karl W.
Published: September 2020

Statistical methods to map quantitative trait loci (QTL) often neglect the X chromosome and may focus exclusively on autosomal loci. But the X chromosome often requires special treatment: sex and cross-direction covariates may need to be included to avoid spurious evidence of linkage, and the X chromosome may require a separate significance threshold. In multiple-QTL analyses, including the consideration of epistatic interactions, the X chromosome also requires special care and consideration. We extend a penalized likelihood method for multiple-QTL model selection, to appropriately handle the X chromosome. We examine its performance in simulation and by application to a large eQTL data set. The method has been implemented in the package R/qtl.
Neural encoding of socially adjusted value during competitive and hazardous foraging
Authors: Silston Brian , Wise Toby , Qi Song , Sui Xin , Dayan Peter , Mobbs Dean
Published: September 2020

In group foraging organisms, optimizing the conflicting demands of competitive food loss and safety is critical. We demonstrate that humans select competition avoidant and risk diluting strategies during foraging depending on socially adjusted value. We formulate a mathematically grounded quantification of socially adjusted value in foraging environments and show using multivariate fMRI analyses that socially adjusted value is encoded by mid-cingulate and ventromedial prefrontal cortices, regions that integrate value and action signals.
Developmental Genetics of Corolla Tube Formation: Role of the tasiRNA-ARF Pathway and a Conceptual Model
Authors: Ding Baoqing , Xia Rui , Lin Qiaoshan , Gurung Vandana , Sagawa Janelle M. , Stanley Lauren E. , Strobel Matthew , Diggle Pamela K. , Meyers Blake C. , Yuan Yao-Wu
Published: September 2020

Over 80,000 angiosperm species produce flowers with petals fused into a corolla tube. The corolla tube contributes to the tremendous diversity of flower morphology and plays a critical role in plant reproduction, yet it remains one of the least understood plant structures from a developmental genetics perspective. Through mutant analyses and transgenic experiments, we show that the tasiRNA-ARF pathway is required for corolla tube formation in the monkeyflower species Mimulus lewisii. Loss-of-function mutations in the M. lewisii orthologs of ARGONAUTE7 and SUPPRESSOR OF GENE SILENCING3 cause a dramatic decrease in abundance of TAS3-derived small RNAs and a moderate upregulation of AUXIN RESPONSE FACTOR3 (ARF3) and ARF4, which lead to inhibition of lateral expansion of the bases of petal primordia and complete arrest of the upward growth of the interprimordial regions, resulting in unfused corollas. Using the DR5 auxin-responsive promoter, we discovered that auxin signaling is continuous along the petal primordium base and the interprimordial region during the critical stage of corolla tube formation in the wild type, similar to the spatial pattern of MlARF4 expression. Auxin response is much weaker and more restricted in the mutant. Furthermore, exogenous application of a polar auxin transport inhibitor to wild-type floral apices disrupted petal fusion. Together, these results suggest a new conceptual model highlighting the central role of auxin-directed synchronized growth of the petal primordium base and the interprimordial region in corolla tube formation.
Exploratory modelling and ranking of the trust factors of messages about organic foods in social networks
Authors: Sobhanifard Yaser , Eshtiaghi Khashayar
Published: September 2020

Purpose

The purpose of this paper is to explore a model and note the ranking of the trust factors of messages about organic food in social networks.

Design/methodology/approach

The research was divided into four phases. The first employed the literature review about Trust, Trust of products, Trust of organic foods and Trust in the social networks. This review was prepared as some hypothesis about the trust of messages about organic food in the social network. The second employed a focused interview to supplement the mentioned hypothesis to 31 factors that affect the trust of messages about organic food in social networks. In the third phase, 300 forms were used to collect information from Iranian consumers for exploratory factor analysis. Finally, neural networks were used to determine the ranking of the mentioned factors.

Findings

The results show 31 factors that affect the trust of messages about organic food in social networks. The results of this study showed that Iranian and international organic foods producers may be able to spread messages of trust about their products in social networks by attending to these 31 factors. This study also explored a model constructed using EFA that showed that six factors have a positive effect on the level of trust of messages about organic food in social networks.

Practical implications

This research effectively helps organic food producers to better understand the trust factors and ways to improve that trust in cyberspace marketing plans and to increase their sales.

Originality/value

For the first time, this research seeks a model for the factors affecting consumer trust in organic foods in social networks, and in the next step, it ranks these factors with artificial neural networks.
Factors affecting online food delivery service in Bangladesh: an empirical study
Authors: Saad Ahmed Tausif
Published: September 2020

Purpose

The core idea of this paper was to empirically evaluate the factors affecting the choices of consumers while ordering food online. The goal was to explore consumer behavior in the emerging industry of online food delivery business in an emerging economy, Bangladesh.

Design/methodology/approach

This paper used a qualitative and exploratory approach through the collection and analysis of data from a total of 177 survey respondents. Statistical analyses of all collected data (utilizing t-tests and factor analysis) were used to conclude the factors important to consumers in ordering food online through online food delivery intermediaries.

Findings

Results showed delivery time, service quality, price and condition of food delivered as factors constitute the first factor considered to be directly affecting the success of online food delivery. Variety and number of restaurants, menu, delivery tracking service and attitude of a delivery person are found to constitute the second factor and considered as indirect factors.

Practical implications

Online food ordering has been a very emerging sector globally and also a recent phenomenon in Bangladesh. The development and the availability of the internet combined with the busy life schedule has prompted businesses to address another need among consumers, the need to deliver foods at consumers' doorsteps. Understanding the consumer landscape better would help realize the full potential of the e-commerce platform as it can influence the economy, businesses and the quality of life of people.

Originality/value

The online food delivery business is new and growing and demands greater researches for better understanding by academicians and practitioners. This paper expands the limited existing research related to the online food delivery business and explores consumer behavior in the industry. From a managerial perspective, the paper contributes to understanding the consumers more broadly.
The impact of access to irrigation on rural incomes and diversification: evidence from China
Authors: Li Junpeng , Ma Wanglin , Renwick Alan , Zheng Hongyun
Published: September 2020

Purpose

The objective of this study is to estimate the impacts of access to irrigation on farm income, household income and income diversification.

Design/methodology/approach

This study employs an endogenous switching regression (ESR) model to address the selection bias arising from both observed and unobserved factors and analyze cross-sectional data collected from Fujian, Henan and Sichuan provinces in China. The authors use the Simpson index to measure household income diversification. The propensity score matching (PSM) model and control function approach are also used for comparison purpose.

Findings

After controlling for the selection bias, the authors find that access to irrigation has a positive and statistically significant impact on rural incomes and diversification. The treatment effects of access to irrigation are to increase farm income, household income and income diversification by around 14, 10 and 107%, respectively. The positive effects of access to irrigation are confirmed by the estimates of the PSM model and control function approach. Further analysis reveals that the irrigation effects on rural incomes and diversification are heterogeneous between small-scale and large-scale farmers and between male-headed and female-headed households.

Practical implications

The authors’ findings suggest that the government should continue to improve irrigation infrastructure construction in rural China to promote smallholder farmers' water access and at the same time facilitate farmers' access to better agronomic and irrigation information. There exist gender and farm size related income and diversification effects of access to irrigation, and the irrigation access is associated with farm location. Thus, when developing regional irrigation programs consideration needs to be taken of whether the rural farming systems are dominated by male/female household heads and land fragmentation/consolidation issues.

Originality/value

Although a large body of literature has investigated the effects of irrigation development in rural areas, little is known about the impact of access to irrigation on income diversification. The selection bias associated with unobserved heterogeneities is usually neglected in previous studies. This study provides the first attempt by examining the impacts of access to irrigation on rural incomes and diversification, using the ESR model to address both observed and unobserved selection bias.
On the quest for defining organisational plasticity: a community modelling experiment
Authors: Siebers Peer-Olaf , Herath Dinuka B. , Bardone Emanuele , Farahbakhsh Siavash , Knudsen Peter Gloggengiehser , Madsen Jens Koed , Mufti Mehwish , Neumann Martin , Richards Dale , Seri Raffaello , Secchi Davide
Published: September 2020

Purpose

This viewpoint article is concerned with an attempt to advance organisational plasticity (OP) modelling concepts by using a novel community modelling framework (PhiloLab) from the social simulation community to drive the process of idea generation. In addition, the authors want to feed back their experience with PhiloLab as they believe that this way of idea generation could also be of interest to the wider evidence-based human resource management (EBHRM) community.

Design/methodology/approach

The authors used some workshop sessions to brainstorm new conceptual ideas in a structured and efficient way with a multidisciplinary group of 14 (mainly academic) participants using PhiloLab. This is a tool from the social simulation community, which stimulates and formally supports discussions about philosophical questions of future societal models by means of developing conceptual agent-based simulation models. This was followed by an analysis of the qualitative data gathered during the PhiloLab sessions, feeding into the definition of a set of primary axioms of a plastic organisation.

Findings

The PhiloLab experiment helped with defining a set of primary axioms of a plastic organisation, which are presented in this viewpoint article. The results indicated that the problem was rather complex, but it also showed good potential for an agent-based simulation model to tackle some of the key issues related to OP. The experiment also showed that PhiloLab was very useful in terms of knowledge and idea gathering.

Originality/value

Through information gathering and open debates on how to create an agent-based simulation model of a plastic organisation, the authors could identify some of the characteristics of OP and start structuring some of the parameters for a computational simulation. With the outcome of the PhiloLab experiment, the authors are paving the way towards future exploratory computational simulation studies of OP.
The relationship between leadership styles and employee-driven innovation: the mediating role of leader–member exchange
Authors: Echebiri Chukwuemeka K. , Amundsen Stein
Published: September 2020

Purpose

The purpose of this study is to explore the association of two opposite leadership styles with employee-driven innovation and how the leader–member exchange mediates these relationships.

Design/methodology/approach

The authors used online surveys administrated in two waves to collect data from 315 employees working in the banking sector in Norway. Exogenous variables, which include empowering and directive leadership styles, were measured at time 1, while the endogenous variables of the leader–member exchange and employee-driven innovation were measured at time 2. The data were analysed using structural equation modelling.

Findings

The findings confirmed that empowering leaders are more likely to have a positive relationship with their subordinates and in turn, stimulate employee-driven innovation. Conversely, the directive leadership style was found to have a negative relationship with the quality of the relationship between leaders and subordinates. It was also found that the association of directive leadership with employee-driven innovation was negative and indirect through the leader–member exchange.

Research limitations/implications

The data for the study were collected from a single organisation, which limits the generalisability of the study. Several other leadership styles were not covered in this study.

Originality/value

This paper provides empirical evidence to support the association between leadership styles and employee-driven innovation. Analyses of these relationship types are unavailable in the employee-driven innovation literature.