bluuebunny/crossref_metadata_2025 huggingface dataset:
CoCoCoNet: Conserved and Comparative Co-expression Across a Diverse Set of Species
Authors: Lee John , Shah Manthan , Ballouz Sara , Crow Megan , Gillis Jesse
Published: April 2020

Co-expression analysis has provided insight into gene function in organisms from Arabidopsis to Zebrafish. Comparison across species has the potential to enrich these results, for example by prioritizing among candidate human disease genes based on their network properties, or by finding alternative model systems where their co-expression is conserved. Here, we present CoCoCoNet as a tool for identifyingconserved gene modules andcomparingco-expressionnetworks. CoCoCoNet is a resource for both data and methods, providing gold-standard networks and sophisticated tools for on-the-fly comparative analyses across 14 species. We show how CoCoCoNet can be used in two use cases. In the first, we demonstrate deep conservation of a nucleolus gene module across very divergent organisms, and in the second, we show how the heterogeneity of autism mechanisms in humans can be broken down by functional groups, and translated to model organisms. CoCoCoNet is free to use and available to all athttps://milton.cshl.edu/CoCoCoNet, with data and R scripts available atftp://milton.cshl.edu/data.
Structural Basis of CD4 Downregulation by HIV-1 Nef
Authors: Kwon Yonghwa , Kaake Robyn , Echeverria Ignacia , Suarez Marissa , Stoneham Charlotte , Ramirez Peter W. , Kress Jacob , Singh Rajendra , Sali Andrej , Krogan Nevan , Guatelli John , Jia Xiaofei
Published: April 2020

The HIV-1 protein Nef suppresses multiple immune surveillance mechanisms to promote viral pathogenesis1. Individuals infected with HIV-1 encoding defectivenefgenes do not develop AIDS for decades2,3. A key target of Nef is the cellular receptor CD4. Although essential for viral entry into host cells, CD4 is problematic for the virus later in its replication cycle: CD4 disrupts processing of the viral glycoprotein, Env, inhibiting infectivity4; it interferes with the release of new virions5,6; and it causes vulnerability to superinfection, causing premature cell death and limiting viral productivity7. Furthermore, binding of CD4 to Env exposes otherwise-concealed Env epitopes, rendering infected cells more susceptible to antibody-dependent cellular cytotoxicity and virus particles more susceptible to neutralizing antibodies8-10. HIV-1 has evolved strategies to mitigate these problems. Newly synthesized CD4 is targeted in the endoplasmic reticulum by the viral Vpu protein for proteasomal degradation11. Surface-expressed CD4, in contrast, is targeted by Nef for endocytosis and lysosomal degradation12-15. Nef’s effect on CD4 involves hijacking of clathrin adaptor complex 2 (AP2)-dependent endocytosis16,17. Although how Nef associates with a part of the tetrameric AP2 is understood18, a complete understanding of the interaction, especially how CD4 is sequestered by Nef into a complex with AP2, has remained elusive. Here, we present a high-resolution crystal structure that describes the underlying mechanism. An intricate combination of conformational changes occurs in both Nef and AP2 to enable CD4 binding and downregulation. Strikingly, a pocket on Nef previously identified as crucial for recruiting class I MHC is also responsible for recruiting CD4, revealing a potential approach to inhibit two of Nef’s activities and sensitize the virus to immune clearance
Population genomics insights into the recent evolution of SARS-CoV-2
Authors: Vasilarou Maria , Alachiotis Nikolaos , Garefalaki Joanna , Beloukas Apostolos , Pavlidis Pavlos
Published: April 2020

The current coronavirus disease 2019 (COVID-19) pandemic is caused by the SARS-CoV-2 virus and is still spreading rapidly worldwide. Full-genome-sequence computational analysis of the SARS-CoV-2 genome will allow us to understand the recent evolutionary events and adaptability mechanisms more accurately, as there is still neither effective therapeutic nor prophylactic strategy. In this study, we used population genetics analysis to infer the mutation rate and plausible recombination events that may have contributed to the evolution of the SARS-CoV-2 virus. Furthermore, we localized targets of recent and strong positive selection. The genomic regions that appear to be under positive selection are largely co-localized with regions in which recombination from non-human hosts appeared to have taken place in the past. Our results suggest that the pangolin coronavirus genome may have contributed to the SARS-CoV-2 genome by recombination with the bat coronavirus genome. However, we find evidence for additional recombination events that involve coronavirus genomes from other hosts, i.e., Hedgehog and Sparrow. Even though recombination events within human hosts cannot be directly assessed, due to the high similarity of SARS-CoV-2 genomes, we infer that recombinations may have recently occurred within human hosts using a linkage disequilibrium analysis. In addition, we employed an Approximate Bayesian Computation approach to estimate the parameters of a demographic scenario involving an exponential growth of the size of the SARS-CoV-2 populations that have infected European, Asian and Northern American cohorts, and we demonstrated that a rapid exponential growth in population size can support the observed polymorphism patterns in SARS-CoV-2 genomes.
Social Stress Alters Immune Response and Results in Higher Viral Load During Acute SIV Infection in a Pigtailed Macaque Model of HIV
Authors: Guerrero-Martin Selena M. , Rubin Leah H. , McGee Kirsten M. , Shirk Erin N. , Queen Suzanne E. , Li Ming , Bullock Brandon , Carlson Bess W. , Adams Robert J. , Gama Lucio , Graham David R. , Zink Christine , Clements Janice E. , Mankowski Joseph L. , Metcalf Pate Kelly A.
Published: April 2020

While social distancing is a key public health response during viral pandemics, social stress, which can be induced by social isolation, has been implicated in adverse health outcomes in general1and in the context of infectious disease, such as HIV2,3. A comprehensive understanding of the direct pathophysiologic effects of social stress on viral pathogenesis is needed to provide strategic and comprehensive care to patients with viral infection. To determine the effect of social stress on HIV pathogenesis during acute viral infection without sociobehavioral confounders inherent in human cohorts, we compared commonly measured parameters of HIV progression between singly and socially housed SIV-infected pigtailed macaques (Macaca nemestrina). Singly housed macaques had a higher viral load in the plasma and cerebrospinal fluid and demonstrated greater CD4 T cell declines and greater CD4 and CD8 T cell activation compared to socially housed macaques throughout acute infection. These data demonstrate that social stress directly impacts the pathogenesis of acute HIV infection and imply that social stress may act as an integral variable in the progression of HIV infection and potentially of other viral infections.
Mechanism of life-long maintenance of neuron identity despite molecular fluctuations
Authors: Traets Joleen J. H. , van der Burght Servaas N. , Jansen Gert , van Zon Jeroen S.
Published: April 2020

Cell fate is maintained over long timescales, yet molecular fluctuations can lead to spontaneous loss of this differentiated state. We uncovered a mechanism that explains life-long maintenance of ASE neuron fate inC. elegansby the terminal selector transcription factor CHE-1. Fluctuations in CHE-1 level are buffered by the reservoir of CHE-1 bound at its target promoters, which ensure continuedche-1expression by preferentially binding theche-1promoter. We validated this mechanism by showing thatche-1expression was resilient to induced transient CHE-1 depletion, while both expression of CHE-1 targets and ASE function were lost. We identified a 130 bpche-1promoter fragment responsible for this resilience, with deletion of a homeodomain binding site in this fragment causing stochastic loss of ASE identity long after its determination. Because network architectures that support this mechanism are highly conserved in cell differentiation, it may explain stable cell fate maintenance in many systems.
The CRP-family transcriptional regulator DevH regulates expression of heterocyst-specific genes at the later stage of differentiation in the cyanobacteriumAnabaenasp. strain PCC 7120
Authors: Kurio Yohei , Koike Yosuke , Kanesaki Yu , Watanabe Satoru , Ehira Shigeki
Published: April 2020

Heterocysts are terminally differentiated cells of filamentous cyanobacteria, which are specialized for nitrogen fixation. Because nitrogenase, an enzyme for nitrogen fixation, is easily inactivated by oxygen, the intracellular environment of heterocysts is kept microoxic. In heterocysts, the oxygen-evolving photosystem II is inactivated, a heterocyst-specific envelope with an outer polysaccharide layer and an inner glycolipid layer is formed to limit oxygen entry, and oxygen consumption is activated. Heterocyst differentiation, which is accompanied by drastic morphological and physiological changes, requires strictly controlled gene expression systems. Here, we investigated the functions of a CRP-family transcriptional regulator, DevH, in the process of heterocyst differentiation. AdevH-knockdown strain, devHKD, was created by replacing the original promoter with thegifApromoter, which is repressed during heterocyst differentiation. Although devHKD formed morphologically distinct cells with the heterocyst envelope polysaccharide layer, it was unable to grow diazotrophically. Genes involved in construction of the microoxic environment, such ascoxoperons and thehglisland, were not upregulated in devHKD. Moreover, expression of thenifgene cluster was completely abolished. Even under anaerobic conditions, thenifgene cluster was not induced in devHKD. Thus, DevH is necessary for the establishment of a microoxic environment and induction of nitrogenase in heterocysts.
Zinc oxide nanoparticles modulate the gene expression of ZnT1and ZIP8to manipulate zinc homeostasis and stress-induced cytotoxicity in human neuroblastoma SH-SY5Y cells
Authors: Pan Chien-Yuan , Lin Fang-Yu , Kao Lung-Sen , Huang Chien-Chang , Liu Pei-Shan
Published: April 2020

Zinc ions (Zn2+) are important messenger molecules involved in various physiological functions. To maintain the homeostasis of cytosolic Zn2+concentration ([Zn2+]c), Zrt/Irt-related proteins (ZIPs) and Zn2+transporters (ZnTs) are the two families of proteins responsible for decreasing and increasing the [Zn2+]c, respectively, by fluxing Zn2+across the membranes of the cell and intracellular compartments in opposite directions. Most studies focus on the cytotoxicity incurred by a high concentration of [Zn2+]cand less investigate the [Zn2+]cat physiological levels. Zinc oxide-nanoparticle (ZnO-NP) is blood brain barrier-permeable and elevates the [Zn2+]cto different levels according to the concentrations of ZnO-NP applied. In this study, we mildly elevated the [Zn2+]cby zinc oxide-nanoparticles (ZnO-NP) at concentrations below 1 μg/ml, which had little cytotoxicity, in cultured human neuroblastoma SH-SY5Y cells and characterized the importance of Zn2+transporters in 6-hydroxy dopamine (6-OHDA)-induced cell death. The results show that ZnO-NP at low concentrations elevated the [Zn2+]ctransiently in 6 hr, then declined gradually to a basal level in 24 hr. Knocking down the expression levels ofZnT1(mostly at the plasma membrane) andZIP8(present in endosomes and lysosomes) increased and decreased the ZnO-NP-induced elevation of [Zn2+]c, respectively. ZnO-NP treatment reduced the basal levels of reactive oxygen species andBax/Bcl-2mRNA ratios; in addition, ZnO-NP decreased the 6-OHDA-induced ROS production,p53expression, and cell death. Therefore, mild elevations in [Zn2+]cinduced by ZnO-NP activate beneficial effects in reducing the 6-OHDA-induced cytotoxic effects. Therefore, brain-delivery of ZnO-NP can be regarded as a potential therapy for neurological disease.
In silicodiscovery and biological validation of ligands of FAD synthase, a promising new antimicrobial target
Authors: Lans Isaias , Anoz-Carbonell Ernesto , Palacio-Rodríguez Karen , Aínsa José Antonio , Medina Milagros , Cossio Pilar
Published: April 2020

New treatments for diseases caused by antimicrobial-resistant microorganisms can be developed by identifying unexplored therapeutic targets and by designing efficient drug screening protocols. In this study, we have screened a library of compounds to find ligands for the flavin-adenine dinucleotide synthase (FADS) -a potential target for drug design against tuberculosis and pneumonia- by implementing a new and efficient virtual screening protocol. The protocol has been developed for thein silicosearch of ligands of unexplored therapeutic targets, for which limited information about ligands or ligand-receptor structures is available. It implements an integrative funnel-like strategy with filtering layers that increase in computational accuracy. The protocol starts with a pharmacophore-based virtual screening strategy that uses ligand-free receptor conformations from molecular dynamics (MD) simulations. Then, it performs a molecular docking stage using several docking programs and an exponential consensus ranking strategy. The last filter, samples the conformations of compounds bound to the target using MD simulations. The MD conformations are scored using several traditional scoring functions in combination with a newly-proposed score that takes into account the fluctuations of the molecule with a Morse-based potential. The protocol was optimized and validated using a compound library with known ligands of theCorynebacterium ammoniagenesFADS. Then, it was used to find new FADS ligands from a compound library of 14,000 molecules. A small set of 17in silicofiltered molecules were tested experimentally. We identified five inhibitors of the activity of the flavin adenylyl transferase mononucleotide of the FADS, and some of them were able to inhibit growth of three bacterial species:Corynebacterium ammoniagenes, Mycobacterium tuberculosis, andStreptococcus pneumoniae, where the former two are human pathogens. Overall, the results show that the integrative VS protocol is a cost-effective solution for the discovery of ligands of unexplored therapeutic targets.

Author summary

Developing cures for antimicrobial-resistant microorganisms is a pressing necessity. Addressing this problem requires the discovery of novel therapeutic targets -for example, bacterial proteins with no human homologues- and the development of cost-effective drug screening protocols. In this work, we tackled the problem on both sides. We developed an efficient and successful integrative computational protocol for screening inhibitory-molecules for unexplored targets. We used it to discover five novel inhibitors of flavin-adenine dinucleotide synthase (FADS), a promising protein target of pathogens causingtuberculosisandpneumonia.
Exploration of bacterial bottlenecks andStreptococcus pneumoniaepathogenesis by CRISPRi-seq
Authors: Liu Xue , Kimmey Jacqueline M. , de Bakker Vincent , Nizet Victor , Veening Jan-Willem
Published: April 2020

Streptococcus pneumoniaeis a commensal bacterium of the human nasopharynx, but can cause harmful infections if it spreads to other parts of the body, such as pneumonia, sepsis or meningitis. To facilitate pathogenesis studies, we constructed a doxycycline-inducible pooled CRISPR interference (CRISPRi) library targeting all operons in protypicalS. pneumoniaestrain D39V. Our library design allows fitness within the pool to be assessed by a one-step PCR reaction directly followed by Illumina sequencing (CRISPRi-seq). The doxycycline-inducible CRISPRi system is tightly controllable and suitable for both bottleneck exploration and evaluation of gene fitnessin vitroandin vivo. Here, we applied CRISPRi-seq to identify genetic factors important for causing pneumococcal pneumonia. Mice were infected intratracheally with our CRISPRi library and bacteria collected at 24 h (from lung) and 48 h (from both lung and blood) post-infection. CRISPRi-seq showed a critical bottleneck at 48 h after intratracheal infection, with only a few bacteria surviving the brunt of the innate immune response to cause systemic infection. However, earlier at 24 h post-infection, many significant differences in gene fitness cost betweenin vitroandin vivoconditions were identified, including genes encoding known and putative novel virulence factors, genes essential onlyin vivo, and genes essential onlyin vitro. A key advantage of CRISPRi-seq over traditional transposon-based genetic screens is that all genes, including essential genes, can be tested for their role in virulence and pathogenicity. The approaches developed here should be generally applicable to study infection bottlenecks andin vivofitness for other important human and animal pathogens.
Multiscale cardiac imaging to capture the whole heart and its internal cellular architecture, with applications to congenital heart disease
Authors: Rykiel Graham , López Claudia S. , Riesterer Jessica L. , Fries Ian , Deosthali Sanika , Courchaine Katherine , Maloyan Alina , Thornburg Kent , Rugonyi Sandra
Published: April 2020

Efficient cardiac pumping depends on the morphological structure of the heart, but also on its sub-cellular (ultrastructural) architecture, which enables cardiac contraction. In cases of congenital heart defects, localized sub-cellular disruptions in architecture that increase the risk of heart failure are only starting to be discovered. This is in part due to a lack of technologies that can image the three dimensional (3D) heart structure, assessing malformations; and its ultrastructure, assessing disruptions. We present here a multiscale, correlative imaging procedure that achieves high-resolution images of the whole heart, using 3D micro-computed tomography (micro-CT); and its ultrastructure, using 3D scanning electron microscopy (SEM). This combination of technologies has not been possible before in imaging the same cardiac sample due to the heart large size, even when studying small fetal and neonatal animal models (~5×5×5mm3). Here, we achieved uniform fixation and staining of the whole heart, without losing ultrastructural preservation (at the nm resolution range). Our approach enables multiscale studies of cardiac architecture in models of congenital heart disease and beyond.
The SCF/KIT pathway implements self-organised epithelial patterning by cell movement
Authors: Chuyen Alexandre , Rulquin Charlotte , Thomé Virginie , Clément Raphaël , Kodjabachian Laurent , Pasini Andrea
Published: April 2020

How individual cell behaviours lead to the emergence of global patterns is poorly understood. In theXenopusembryonic epidermis, multiciliated cells (MCCs) are born in a random pattern within an inner mesenchymal layer, and subsequently intercalate at regular intervals into an outer epithelial layer. Using both experiments and mathematical modelling, we show that this transition from chaotic to ordered distribution relies on mutual repulsion among motile immature MCCs, and affinity towards outer-layer intercellular junctions. Consistently, ARP2/3-mediated actin remodelling is required for MCC pattern emergence. Using multiple functional approaches, we show that the Kit tyrosine kinase receptor, expressed in MCCs, and its ligand Scf, expressed in outer-layer cells, are both required for regular MCC distribution. While Scf behaves as a potent adhesive cue for MCCs, Kit expression is sufficient to confer order to a disordered heterologous cell population. Our work reveals how a single signalling system can implement self-organised large-scale patterning.

Highlights

- Immature multiciliated cells transit from a disordered to an ordered pattern

- The transition is a self-organising process based on repulsive and affinity movements

- ARP2/3-dependent actin remodelling is required for pattern emergence

- The SCF/KIT pathway promotes both repulsion and affinity movements

eTOC blurb

In developingXenopusepidermis, immature multiciliated cells (MCCs), initially chaotically distributed within an inner layer, emerge in an orderly pattern among cells of the outer layer. This process involves MCC mutual repulsion and affinity towards outer-layer intercellular junctions. The SCF/KIT signalling pathway promotes both properties to allow regular MCC distribution.
FAM111A regulates replication origin activation and cell fitness
Authors: Rios-Szwed Diana O. , Garcia-Wilson Elisa , Sanchez-Pulido Luis , Alvarez Vanesa , Jiang Hao , Bandau Susanne , Lamond Angus , Ponting Chris P. , Alabert Constance
Published: April 2020

FAM111A is a replisome associated protein and dominant mutations within its trypsin-like peptidase domain are linked to severe human developmental syndromes. However, FAM111A functions and its putative substrates remain largely unknown. Here, we showed that FAM111A promotes origin activation and interacts with the putative peptidase FAM111B, and we identified the first potential FAM111A substrate, the suicide enzyme HMCES. Moreover, unrestrained expression of FAM111A wild-type and patient mutants impaired DNA replication and caused cell death only when the peptidase domain remained intact. Altogether our data reveal how FAM111A promotes DNA replication in normal conditions and becomes harmful in a disease context.
Identification of essential genes forEscherichia coliaryl polyene biosynthesis and function in biofilm formation
Authors: Johnston Isabel , Osborn Lucas J , Markley Rachel L , McManus Elizabeth A , Kadam Anagha , Schultz Karlee B , Nagajothi Nagashreyaa , Ahern Philip P , Brown J Mark , Claesen Jan
Published: April 2020

Aryl polyenes (APEs) are specialized polyunsaturated carboxylic acids that were identifiedin silicoas the product of the most widespread family of bacterial biosynthetic gene clusters (BGCs). They are present in several Gram-negative host-associated bacteria, including multi-drug resistant human pathogens. Here, we characterize a biological function of APEs, focusing on the BGC from a uropathogenicEscherichia coli(UPEC) strain. We first perform a genetic deletion analysis to identify the essential genes required for APE biosynthesis. Next, we show that APEs function as fitness factors that increase protection from oxidative stress and contribute to biofilm formation. Together, our study highlights key steps in the APE biosynthesis pathway that can be explored as potential drug targets for complementary strategies to reduce fitness and prevent biofilm formation of multi-drug resistant pathogens.
Axin-mediated regulation of lifespan and muscle health inC. elegansinvolves AMPK-FOXO signaling
Authors: Mallick Avijit , Ranawade Ayush , Gupta Bhagwati P
Published: April 2020

Aging is a significant risk factor for several diseases. Studies have uncovered multiple signaling pathways that modulate the process of aging including the Insulin/IGF-1 signaling (IIS). InC. elegansthe key regulator of IIS is DAF-16/FOXO whose activity is regulated by phosphorylation. A major kinase involved in DAF-16-mediated lifespan extension is the AMPK catalytic subunit homolog, AAK-2. In this study, we demonstrate a novel role of PRY-1/Axin in AAK-2 activation to regulate DAF-16 function. Thepry-1transcriptome contains many genes associated with aging and muscle function. Consistent with this,pry-1is strongly expressed in muscles and muscle-specific overexpression ofpry-1extends the lifespan, delays muscle aging, and improves mitochondrial morphology in DAF-16-dependent manner. Furthermore, PRY-1 is necessary for AAK-2 phosphorylation. Together, our data demonstrate a crucial role of PRY-1 in maintaining the lifespan and muscle health. Since muscle health declines with age, our study offers new possibilities to manipulate Axin function to delay muscle aging and improve lifespan.
Host association induces genome changes inCandida albicanswhich alters its virulence
Authors: Smith Amanda C. , Hickman Meleah A.
Published: April 2020

Candida albicansis an opportunistic fungal pathogen of humans that is typically diploid yet, has a highly labile genome that is tolerant of large-scale perturbations including chromosomal aneuploidy and loss-of-heterozygosity events. The ability to rapidly generate genetic variation is crucial forC. albicansto adapt to changing or stress environments, like those encountered in the host. Genetic variation occurs via stress-induced mutagenesis or can be generated through its parasexual cycle, which includes mating between diploids or stress-induced mitotic defects to produce tetraploids and non-meiotic ploidy reduction. However, it remains largely unknown how genetic background contributes toC. albicansgenome instabilityin vitroorin vivo.Here, we tested how genetic background, ploidy and host environment impactC. albicansgenome stability. We found that host association induced both loss-of-heterozygosity events and genome size changes, regardless of genetic background or ploidy. However, the magnitude and types of genome changes varied acrossC. albicansstrains. We also assessed whether host-induced genomic changes resulted in any consequences on growth rate and virulence phenotypes and found that many host derived isolates had significant changes compared to their parental strains. Interestingly, host derivatives from diploidC. albicanspredominantly displayed increased virulence, whereas host derivatives from tetraploidC. albicanshad mostly reduced virulence. Together, these results are important for understanding how host-induced genomic changes inC. albicansalter the relationship between the host andC. albicans.
BLOS1 mediates kinesin switch during endosomal recycling of LDL receptor
Authors: Zhang Chang , Hao Chanjuan , Shui Guanghou , Li Wei
Published: April 2020

Low-density lipoprotein receptor (LDLR) in hepatocytes plays a key role in normal clearance of circulating LDL and in whole body cholesterol homeostasis. The trafficking of LDLR is highly regulated in clathrin-dependent endocytosis, endosomal recycling and lysosomal degradation. Current studies have been focusing on its endocytosis and degradation. However, the detailed molecular and cellular mechanisms underlying its endosomal recycling are largely unknown. We found that BLOS1, a shared subunit of BLOC-1 and BORC, is involved in LDLR endosomal recycling. Loss of BLOS1 leads to less membrane LDLR and impairs LDL clearance from plasma in hepatocyte-specific BLOS1 knockout mice. BLOS1 interacts with kinesin-3, and that BLOS1 acts as a new adaptor for kinesin-2 to coordinate kinesin-3 and kinesin-2 during the long-range transport of recycling endosomes (REs) to plasma membrane along microtubule tracks to overcome hurdles at microtubule intersections. These findings provide new insights into RE’s anterograde transport and the pathogenesis of dyslipidemia.
Regulation of blood cell transdifferentiation by oxygen sensing neurons
Authors: Corcoran Sean , Mase Anjeli , Hashmi Yousuf , Ouyang Debra , Augsburger Jordan , Jacobs Thea , Kukar Katelyn , Brückner Katja
Published: April 2020

Transdifferentiation generates specialized cell types independent of stem or progenitor cells. Despite the unique process, it remains poorly understood how transdifferentiation is regulated in vivo. Here we reveal a mechanism of environmental control of blood cell transdifferentiation in aDrosophilamodel of hematopoiesis. Functional lineage tracing provides evidence for transdifferentiation from macrophage-like plasmatocytes to crystal cells that execute melanization. Interestingly, this transdifferentiation is promoted by neuronal activity of a specific subset of sensory neurons, in the caudal sensory cones of the larva. Crystal cells develop from plasmatocyte clusters surrounding the sensory cones, triggered by environmental conditions: oxygen sensing, and the atypical guanylyl cyclase Gyc88E specifically expressed in the sensory cone neurons, drive plasmatocyte-to-crystal cell transdifferentiation. Our findings reveal an unexpected functional and molecular link of environment-monitoring sensory neurons that govern blood cell transdifferentiation in vivo, suggesting similar principles in vertebrate systems where environmental sensors and blood cell populations coincide.

Highlights

Functional lineage tracing reveals in vivo transdifferentiation in aDrosophilamodel of hematopoiesis

Active sensory neurons of the caudal sensory cones promote blood cell transdifferentiation in theDrosophilalarva

Environmental oxygen sensing and atypical guanylyl cyclase activity in sensory cone neurons drive blood cell transdifferentiation
Vasohibin-1 mediated tubulin detyrosination selectively regulates secondary sprouting and lymphangiogenesis in the zebrafish trunk
Authors: de Oliveira Marta Bastos , Katja Meier , Baptiste Coxam , Ilse Geudens , Simone Jung , Anna Szymborska , Holger Gerhardt
Published: April 2020

Previous studies have shown that Vasohibin-1 (Vash-1) is stimulated by VEGFs in endothelial cells and that its overexpression interferes with angiogenesisin vivo. Recently, Vasohibin-1 was found to mediate tubulin detyrosination, a post-translational modification that is implicated in many cell functions, such as cell division. Here we used the zebrafish embryo to investigate the cellular and subcellular mechanisms of Vash-1 on endothelial microtubules during formation of the trunk vasculature. We show that microtubules within venous-derived secondary sprouts are strongly and selectively detyrosinated in comparison with other endothelial cells, and that this difference is lost uponvash-1knockdown. Vasohibin-1 depletion in zebrafish specifically affected secondary sprouting from the posterior cardinal vein, increasing both the number of sprouts and endothelial cell divisions. We show that altering secondary sprout numbers and structure uponvash-1depletion leads to a failure in the development and specification of lymphatic vessels of the zebrafish trunk.

Vasohibin-1 mediated detyrosination of endothelial microtubules is selectively required for adequate behaviour of venous secondary sprouting and subsequent formation of functional lymphatics in the zebrafish trunk.
The EccDNA Replicon: A Heritable, Extranuclear Vehicle That Enables Gene Amplification and Glyphosate Resistance in Amaranthus palmeri
Authors: Molin William T. , Yaguchi Allison , Blenner Mark , Saski Christopher A.
Published: April 2020

Gene copy number variation is a predominant mechanism used by organisms to respond to selective pressures from the environment. This often results in unbalanced structural variations that perpetuate as adaptations to sustain life. However, the underlying mechanisms that give rise to gene proliferation are poorly understood. Here, we show a unique result of genomic plasticity in Amaranthus palmeri: a massive, ~400-kb extrachromosomal circular DNA (eccDNA) that harbors the 5-ENOYLPYRUVYLSHIKIMATE-3-PHOSPHATE SYNTHASE (EPSPS) gene and 58 other genes whose encoded functions traverse detoxification, replication, recombination, transposition, tethering, and transport. Gene expression analysis under glyphosate stress showed transcription of 41 of these 59 genes, with high expression of EPSPS, as well as genes coding for aminotransferases, zinc finger proteins, and several uncharacterized proteins. The genomic architecture of the eccDNA replicon is composed of a complex arrangement of repeat sequences and mobile genetic elements interspersed among arrays of clustered palindromes that may be crucial for stability, DNA duplication and tethering, and/or a means of nuclear integration of the adjacent and intervening sequences. Comparative analysis of orthologous genes in grain amaranth (Amaranthus hypochondriacus) and waterhemp (Amaranthus tuberculatus) suggests that higher order chromatin interactions contribute to the genomic origins of the A. palmeri eccDNA replicon structure.
CrystalCMP: automatic comparison of molecular structures
Authors: Rohlíček Jan , Skořepová Eliška
Published: April 2020

This article describes new developments in the CrystalCMP software. In particular, an automatic procedure for comparison of molecular packing is presented. The key components are an automated procedure for fragment selection and the replacement of the angle calculation by root-mean-square deviation of atomic positions. The procedure was tested on a large data set taken from the Cambridge Structural Database (CSD) and the results of all the comparisons were saved as an HTML page, which is freely available on the web. The analysis of the results allowed estimation of the threshold for identification of identical packing and allowed duplicates and entries with potentially incorrect space groups to be found in the CSD.
Assessing resilience against floods with a system dynamics approach: a comparative study of two models
Authors: Feofilovs Maksims , Romagnoli Francesco , Gotangco Charlotte Kendra , Josol Jairus Carmela , Jardeleza Jean Meir Perez , Litam Joseph Emanuel , Campos Joaquin Ignacio , Abenojar Katrina
Published: April 2020

Purpose

This paper aims to present the concepts of two different ways of generating a dynamic structure of the urban system to further allow in understanding specific urban behavior facing against flood and further evaluate the potential effect of specific resilience strategies aiming to decrease the exposure and vulnerability of the system.

Design/methodology/approach

Two system dynamics model structures are presented in form of Casual Loop Diagrams.

Findings

The main differences among the tow approaches are the time horizon and the approach that regulates the assessment of the resilience through a dynamic composite indicator: the first model refers to baseline at initial simulation time; the second model is focused on the ratio service supply to demand.

Research limitations/implications

Within the approach, the purpose is to properly and efficiently evaluate the effect of different Flood Risk Management strategies, i.e. prevention, defence, mitigation, preparation and recovery for consistent and resilient flood governance plans with different type of resilience scenarios.

Originality/value

The need for such tool is underlined by a lack on the assessment of urban resilience to flood as whole, considering the physical and social dimensions and the complex interaction among their main components. There are several assessment tools based on an indicator approach that have been proposed to meet this need. Nevertheless, indicator-based approach has the limitation to exclude the complexity of the system and its systemic interaction in terms of feedbacks’ effects among the identified components or variables selected for the system description. This peculiarity can be provided by System Dynamics modeling.
Supervisor support, work engagement and turnover intentions: evidence from Indian call centres
Authors: Pattnaik Subash Chandra , Panda Narendra
Published: April 2020

Purpose

This paper aims to examine the relationship between supervisor support, work engagement and turnover intentions with work engagement playing the role of a mediator.

Design/methodology/approach

Data from 386 Indian call centre employees through questionnaire survey was collected. A variety of statistical tools such as confirmatory factor analysis, Sobel test and descriptive statistics were used for examining the relationship.

Findings

From this study, it was found that work engagement partially mediates the relationship between supervisor support and turnover intentions confirming well with the model hypothesized for the study.

Originality/value

Both employee turnover and disengagement levels in call centres keep on increasing, but very little research has been conducted so far on the linkage between supervisor support, work engagement and turnover intentions. Whatever little research has been conducted so far does not take supervisor support as a one-dimensional construct, thus obscuring its impact on work engagement and turnover intentions. That too, the findings about the relationship between work engagement and turnover intentions are mixed, thus calling for further studies. Moreover, the majority of the studies so far have come from Western contexts. The relationship is yet to be fully understood in the emerging Asian business context.
The influence of multi-stakeholder platforms on farmers' innovation and rural development in emerging economies: a systematic literature review
Authors: Barzola Iza Carlos L , Dentoni Domenico , Omta Onno S.W.F.
Published: April 2020

Purpose

Despite the increasing interest on multi-stakeholder platforms (MSPs) as novel organizational forms addressing grand challenges surrounding agri-food systems, the literature on how MSPs influence farmers' innovation remains scattered across sub-disciplines and geographies and, overall, of limited help for informing managerial and policy action and reflection.

Design/methodology/approach

To address this gap, this systematic literature review (SRL) provides an overview on what MSPs are and how they influence farmers' innovation in emerging economies.

Findings

The selected sample included n = 44 publications in 2004–2018, focussing for 70% on Africa, with minor shares in Latin America and Asia, and with a strong theoretical and methodological segmentation across five sub-disciplines (agribusiness management, agricultural economics, agricultural innovation systems, agricultural research for development and public policy and governance). Overall, this SRL leads to three findings. First, a key distinctive organizational feature of MSPs relative to other novel organizational forms in emerging economies entails the presence of a virtual and/or physical interface spanning across multiple heterogeneous stakeholders. Second, in relation to their impact pathways towards farmers' innovation, MSPs tend to achieve different intermediary outcomes and levels of innovation depending on their organizational goals and activities.

Research limitations/implications

These findings also reveal four key limitations of the extant MSP literature – namely, disciplinary silos thinking, linear thinking, limited focus on the role of informal institutions and little emphasis on power dynamics – which could inform managers and policy makers on how MSPs could influence farmers; innovation.

Originality/value

This study offers a SLR with the goal of providing practitioners and academics with first, a holistic view of the available research on the impact of MSPs on farmers innovation, and second, propose an impact pathway framework to understand how and under which circumstances MSPs support farmers' innovation given their functioning, structure and the governance mechanisms of MSPs.
Dealing with the visibility created by accounting numbers – A case study of cost accounting translation in a transitional economy
Authors: Albu Catalin Nicolae , Albu Nadia , Guinea Flavius Andrei , Tsamenyi Mathew
Published: April 2020

Purpose

This paper investigates the process of translating a costing tool into operational use in the context of a transitional (post-communist) economy, where local institutions challenge the rationality of western methods.

Design/methodology/approach

By mobilizing Actor–Network Theory, in particular Callon's four moments of translation, and by drawing data from an interventionist research, the paper focuses on the process of change instilled by the implementation of a costing tool in 20 Romanian construction companies.

Findings

The costing system is initially problematized as a tool for rational decision making. However, the visibility over the accounting figures generated by the costing tool instilled new roles for the cost system to manage internal and external interdependencies. First, two costing datasets were created, one for decision making and one for tax purposes, to manage the relationship with the state taxation authorities. Second, since the costing tool generated visibility over the field practices as well, engineers convinced management to drop the decision-making set of costs. The costing tool ultimately only became used for tax optimization, an originally unintended use, reflecting its translation process.

Research limitations/implications

By taking an interventionist approach, the paper contributes to theorizing accounting in transitional economies by bringing their economic idiosyncrasies into the analysis.

Practical implications

The results inform managers about the intended and unintended consequences of management accounting tools and about actors' role in shaping their use.

Originality/value

Our research responds to recent calls to study how organizations configure their control systems in a rapidly changing environment and what is the role of management accounting in these arrangements.
Social Media use and value creation in the digital landscape: a dynamic-capabilities perspective
Authors: Garrido-Moreno Aurora , García-Morales Víctor , King Stephen , Lockett Nigel
Published: April 2020

Purpose

Although Social Media use has become all-pervasive, previous research has failed to explain how to use Social Media tools strategically to create business value in today's increasingly digital landscapes. Adopting a dynamic capabilities perspective, this paper empirically examines the specific process through which Social Media use translates into better performance and the capabilities involved in this process.

Design/methodology/approach

A research model is proposed that includes both antecedents and consequences of Social Media use. Existing research was examined to derive the research hypotheses, which were tested using SEM methodology on a sample of 212 hotels.

Findings

The results show that Social Media use does not exert significant direct impact on organizational performance. Rather, the findings confirm the mediating role played by Social CRM and Customer Engagement capabilities in the value creation process.

Practical implications

The results demonstrate how Social Media tools should be implemented and managed to generate business value in hotels. Implications yield interesting insights for hotel managers

Originality/value

This study is a first attempt to analyze empirically the real impact of digital media technologies, particularly Social Media use, drawing on the dynamic capabilities perspective and focusing on service firms (hotels). Including the variable “Organizational Readiness” as a basic prerequisite to benefit from Social Media use enhances the study's novelty and contribution.
Subcutaneous granuloma annulare on the heel: A case report and review of the Japanese published work
Authors: Endo Yukie , Sekiguchi Akiko , Motegi Sei‐ichiro , Ishikawa Osamu
Published: April 2020

Subcutaneous granuloma annulare is a rare variant of granuloma annulare. It mostly presents as painless subcutaneous nodule(s) with or without annular lesions on the lower legs and scalp of children. We herein report a case of a 5‐year‐old Japanese girl with subcutaneous granuloma annulare on the right heel. The lesions improved in 15 months without any therapy. We also review 85 reported cases of subcutaneous granuloma annulare between 1 and 85 years of age in the Japanese published work. The most susceptible age was 5 years and below; however, a small peak occurred from the 40s to 60s. Subcutaneous granuloma annulare was more frequent in females (male : female ratio, 6:11). Sixty‐five cases (76.4%) had multiple lesions; the average number of lesions was 4.8 ± 5.8. The most affected site was the lower legs (28 cases), followed by the dorsum of the foot (21 cases) and scalp (17 cases). The heel was an unusual location; only two cases of sole subcutaneous granuloma annulare have been reported. Twenty‐one cases revealed a classical dermal change along with a subcutaneous change. Patients with classical dermal lesions were younger (P < 0.0001) and had a smaller number of lesions (P < 0.05) than those without the lesions. The lesion(s) resolved in 24 of the 44 untreated cases within 1 week to 19 months. Refractory or recurrent lesion(s) were seen in four of 21 treated cases and in four of 44 untreated cases. Because subcutaneous granuloma annulare lesions often resolve spontaneously without treatment, invasive treatments should be avoided.
Complex biotic interactions mediated by shrubs: Revisiting the stress‐gradient hypothesis and consequences for tree seedling survival
Authors: Guignabert Arthur , Augusto Laurent , Gonzalez Maya , Chipeaux Christophe , Delerue Florian
Published: April 2020

Using nurse shrubs to improve tree seedling establishment in stressed environments is a common practice in forestry. Recent refinements of the stress‐gradient hypothesis suggest that positive nurse effects occur under intermediate stress and decline in the harshest conditions. Additionally, indirect facilitation (e.g. protection from herbivory) is expected in low‐stressed/productive systems according to the initial stress‐gradient hypothesis. However, there have been fewer investigations into the use of nurse shrubs to decrease herbivore impacts in stressed systems compared with the role of nurses in stress alleviation. This raises the need to clarify conditions in which the use of nurse shrubs would be most appropriate.

We conducted a field experiment in the sand dune forest of southwest France characterized by severe summer water shortages and the presence of different types of wild herbivores. In 2015 and 2016, Pinus pinaster seedlings were planted under shrubs Arbutus unedo or in shrub‐removed locations, in fenced/unfenced areas. Survival, cause of mortality and water stress were monitored for 1 year after plantation.

Summer drought was the main cause of mortality. Water stress increased in both years as summer progressed. We found direct facilitation only in July 2016 at intermediate water stress, due to a decrease in vapour pressure deficit under shrubs. These positive effects declined in late summer when stress was at a maximum. Rodent damage occurred under shrubs in spring whereas ungulate browsing was observed in open areas in autumn/winter. Overall seedling survival was equivalent under or outside shrubs during the first year, but was better under shrubs in the second one.

Synthesis and applications. Our results partially validate the refinement of the stress‐gradient hypothesis, with a decline of positive interactions in the most water‐stressed conditions. This draws attention to the difficulty of using shrubs as nurses to improve tree regeneration in the most xeric systems. In addition, we show that indirect associational effects, both positive and negative, could be as important as abiotic stress alleviation in a stressful ecosystem, and using shrubs to facilitate seedling survival could be efficient depending on the type of herbivore involved. This highlights the fact that considering plant–plant interactions can help in the design of management options, providing that up‐to‐date ecological theories are considered and that the different biotic and abiotic constraints are accurately evaluated.
The Postcapitalist Transition: Policy Implications for the Left
Authors: Mason Paul
Published: April 2020

The postcapitalism thesis asserts that open source and collaborative non‐profit organisations represent a new, non‐market sector in which the profit motive and monetary exchange no longer drive economic activity; in Marxist political economy terms, they are a new means for suppressing the law of value. Information technology has produced four systemic dysfunctions, limiting capitalism’s ability to function as a complex adaptive system: the zero marginal cost effect, the tendency to delink work from wages, positive network effects, and information asymmetries. In response, in addition to the traditional remedies of social democracy for a stagnant neoliberal economic model, left parties must adopt a programme of transition: aggressively breaking up technological monopolies; promoting universal basic income and basic service solutions; outlawing rent‐seeking business models; and promoting data democracy.