bluuebunny/crossref_metadata_2025 huggingface dataset:
A central role of sibling sRNAs NgncR_162/163 in main metabolic pathways of Neisseria gonorrhoeae
Authors: Steiner Thomas , Zachary Marie , Bauer Susanne , Müller Martin J. , Krischke Markus , Radziej Sandra , Klepsch Maximilian , Huettel Bruno , Eisenreich Wolfgang , Rudel Thomas , Beier Dagmar
Published: May 2022

Bacterial regulatory RNAs (sRNAs) have been implicated in the regulation of numerous metabolic pathways. In most of these studies, sRNA-dependent regulation of mRNAs or proteins of enzymes in metabolic pathways has been predicted to affect the metabolism of these bacteria. However, only in very few cases has the role in metabolism been demonstrated. We performed here a combined transcriptome and metabolome analysis to define the regulon of the sibling sRNAs NgncR_162 and NgncR_163 and their impact on the metabolism of the major human pathogen Neisseria gonorrhoeae. These sRNA have previously been shown to control genes of the citric acid and methylcitrate cycle by post-transcriptional negative regulation. By transcriptome analysis we expand the NgncR_162/163 regulon by several new members and provide evidence that the sibling sRNAs act as both negative and positive regulators of target gene expression. Newly identified NgncR_162/163 targets are mostly involved in transport processes, especially the uptake of glycine, branched chain amino acids and phenylalanine. NgncR_162/163 also play key roles in the control of serine-glycine metabolism and hence probably affect biosynthesis of nucleotides, vitamins and other amino acids via the supply of C1-units. Metabolic flux analysis demonstrated a bipartite metabolism with glucose degradation providing intermediates for anabolic pathways, while energy metabolism via the citric acid cycle is mainly driven by amino acids, which feed into the cycle. Thus, by combined RNA-seq and metabolomics we significantly extended the regulon of NgncR_162/163 and demonstrate their role in the regulation of central metabolic pathways of the gonococcus.

Importance

Neisseria gonorrhoeae is a major human pathogen which infects more than 100 million people every year. An alarming development is the emergence of gonococcal strains resistant against virtually all of the antibiotics used for their treatment. Despite the medical importance and the vanishing treatment options of gonococcal infections, the bacterial metabolism and its regulation is only ill defined until today. We investigate here the regulation of the gonococcal metabolism by two previously studied sRNAs, NgncR_162/163 using RNA-seq and metabolomics. The results provided in this study demonstrate the regulation of transport processes and metabolic pathways involved in the biosynthesis of nucleotides, vitamins and amino acids by NgncR_162/163. Combined transcriptome and metabolome analyses provide a thus far unreached depth in the regulation of metabolic pathways by the neisserial sibling sRNAs and may therefore also be suitable for functional analysis of a growing number of other bacterial metabolic sRNA regulators.
The transcription regulator Lmo3 is required for cell fate specification in the external globus pallidus
Authors: Biswas Shiona , Chan C. Savio , Rubenstein John L.R. , Gan Lin
Published: May 2022

The external globus pallidus (GPe) is an essential component of the basal ganglia, a group of subcortical nuclei that are involved in control of action. Changes in the firing of GPe neurons are associated with both passive and active body movements. Aberrant activity of GPe neurons has been linked to motor symptoms of a variety of movement disorders, such as Parkinson’s Disease, Huntington’s disease and dystonia. Recent studies have helped delineate functionally distinct sub types of GABAergic GPe projection neurons. However, little remains known about specific molecular mechanisms underlying the development of GPe neuronal subtypes. We show that the transcriptional regulator Lmo3 is required for the development of medial ganglionic eminence derived Nkx2.1+ and PV+ GPe neurons, but not FoxP2+ neurons or Npas1+ neurons. As a consequence of the reduction in PV+ neurons, Lmo3-null mice have a reduced pallidal input to the subthalamic nucleus.

SIGNIFICANCE STATEMENT

The external globus pallidus (GPe) is a critical component of the basal ganglia and can coordinate neuronal activity across the basal ganglia by virtue of its widespread projections to almost all other basal ganglia nuclei. Aberrant activity of GPe neurons has been linked to motor symptoms of a wide variety of movement disorders. Recent advances have delineated functionally distinct sub types of GABAergic GPe projection neurons. However, little remains known about molecular mechanisms underlying their development. Here, we demonstrate that the transcription regulator Lmo3 is required for the development of specific subtypes of GPe neurons, and for their appropriate connectivity with other parts of the basal ganglia.
Coiling of cellular protrusions around extracellular fibers
Authors: Sadhu Raj Kumar , Hernandez-Padilla Christian , Eisenbach Yael Eshed , Zhang Lixia , Vishwasrao Harshad D , Behkam Bahareh , Shroff Hari , Iglič Aleš , Peles Elior , Nain Amrinder S. , Gov Nir S
Published: May 2022

Protrusions at the leading-edge of a cell play an important role in sensing the extracellular cues, during cellular spreading and motility. Recent studies provided indications that these protrusions wrap (coil) around the extra-cellular fibers. The details of this coiling process, and the mechanisms that drive it, are not well understood. We present a combined theoretical and experimental study of the coiling of cellular protrusions on fibers of different geometry. Our theoretical model describes membrane protrusions that are produced by curved membrane proteins that recruit the protrusive forces of actin polymerization, and identifies the role of bending and adhesion energies in orienting the leading-edges of the protrusions along the azimuthal (coiling) direction. Our model predicts that the cell’s leading-edge coils on round fibers, but the coiling ceases for a fiber of elliptical (flat) cross-section. These predictions are verified by 3D visualization and quantitation of coiling on suspended fibers using Dual-View light-sheet microscopy (diSPIM). Overall, we provide a theoretical framework supported by high spatiotemporal resolution experiments capable of resolving coiling of cellular protrusions around extracellular fibers of varying diameters.

Significance Statement

Cells adhere and migrate in environments that are composed of fibrous structures, such as the thin filaments of the extracellular matrix, or the wider axons and dendrites of neurons. In recent experiments, cells have been observed to form leading edge protrusions on such surfaces, that seem to coil around the extracellular fibers. However, the mechanism responsible for the formation of such coiling protrusions is not understood. Here, we provide a combined experimental and theoretical approach to explain the emergence of coiling protrusions. Our model is based on the self-organization of curved proteins that recruit actin polymerization at the leading edge of the cell, when spreading over an adhesive fiber.
Decreased miRNA-148a-3p expression in skeletal muscle of patients with chronic kidney disease
Authors: Robinson KA , Baker LA , Graham-Brown MPM , Ashford RU , Pawlyckz Izabella , Major RW , Burton JO , Sylvius N. , Cooper A , Philp A , Watson EL
Published: May 2022

Introduction

Skeletal muscle wasting is a common complication of chronic kidney disease which leads to a loss of muscle function. The pathogenesis of skeletal muscle wasting is incompletely understood, which is preventing the development of targeted therapeutics. Recent evidence implicates miRNAs in the of skeletal muscle wasting. Our aim was to firstly examine miRNA profiles of CKD human skeletal muscle for the identification of aberrant expression patterns compared to a healthy control (HC) cohort, and secondly, investigate the role these miRNAs may play in inducing or promoting skeletal muscle atrophy using a novel human primary skeletal muscle cell model of CKD skeletal muscle.

Methods

For the comparison between CKD and HC populations, skeletal muscle biopsies were collected from the vastus lateralis of n=15 non-dialysis dependent CKD patient’s stage 3b-5 CKD patients, and n=15 healthy controls matched for age, gender and physical activity. n=5 biopsies from each group underwent next generation sequencing to obtain complete microRNA profiles in CKD vs HC cohorts, which were then validated in a separate cohort by PCR (N=10 in each group). A causative role in muscle wasting was determined by transfection of key microRNAs into a primary culture model of CKD skeletal muscle and changes in protein degradation determined by L-[3H]- phenylalanine release into the media.

Results

Next Generation Sequencing identified differential expression of 16 miRNAs in skeletal muscle of CKD patients versus controls, and PCR validation confirmed miRNA-148a-3p expression was significantly decreased in CKD patients. The reduced miRNA-148a-3p expression was also maintained in the primary culture model. Upon overexpression of miRNA-148a-3p in CKD myotubes, protein degradation rates were decreased non-significantly (p=0.28) by 16.3% compared to un-transfected CKD cells.

Conclusion

CKD was associated with a significant reduction in miRNA-148a-3p expression in skeletal muscle compared to non-CKD controls which was retained in our in vitro model. Overexpression of miRNA-148a-3p in primary skeletal myotubes non-significantly decreased muscle protein degradation by 16.3%. In order to determine the importance of miRNA-148a-regulation of protein degradation, a deeper understanding of miRNA-148a-3p targets and their associated pathways with respect to those dysregulated in skeletal muscle wasting is required.
“A CRISPR-dCas13 RNA-editing tool to study alternative splicing”
Authors: Núñez-Álvarez Yaiza , Espie--Caullet Tristan , Buhagiar Géraldine , Rubio-Zulaika Ane , Alonso-Marañón Josune , Perez-Luna Elvira , Blazquez Lorea , Luco Reini F.
Published: May 2022

Alternative splicing allows multiple transcripts to be generated from the same gene to diversify the protein repertoire and gain new functions despite a limited coding genome. It can impact a wide spectrum of biological processes, including disease. However, its significance has long been underestimated due to limitations in dissecting the precise role of each splicing isoform in a physiological context. Furthermore, identifying key regulatory elements to correct deleterious splicing isoforms has proven equally challenging, increasing the difficulty to tackle the role of alternative splicing in cell biology. In this work, we take advantage of dCasRx, a catalytically inactive RNA targeting CRISPR-dCas13 ortholog, to efficiently switch alternative splicing patterns of endogenous transcripts without affecting overall gene expression levels in a cost-effective manner. Additionally, we demonstrate a new application for the dCasRx splice-editing system to identify key regulatory RNA elements of specific splicing events. With this approach, we are expanding the RNA toolkit to better understand the regulatory mechanisms underlying alternative splicing and its physiological impact in various biological processes, including pathological conditions.
Discovery of a new class of reversible TEA-domain transcription factor inhibitors with a novel binding mode
Authors: Hu Lu , Sun Yang , Liu Shun , Erb Hannah , Singh Alka , Mao Junhao , Luo Xuelian , Wu Xu
Published: May 2022

The TEA domain (TEAD) transcription factor forms a transcription co-activation complex with the key downstream effector of the Hippo pathway, YAP/TAZ. TEAD-YAP controls the expression of Hippo-responsive genes involved in cell proliferation, development, and tumorigenesis. Hyperactivation of TEAD-YAP activities is observed in many human cancers, and is associated with cancer cell proliferation, survival and immune evasion. Therefore, targeting the TEAD-YAP complex has emerged as an attractive therapeutic approach. We previously reported that the mammalian TEAD transcription factors (TEAD1-4) possess auto-palmitoylation activities and contain an evolutionarily conserved palmitate-binding pocket (PBP), which allows small molecule modulation. Since then, several reversible and irreversible inhibitors have been reported by binding to PBP. Here, we report a new class of TEAD inhibitors with a novel binding mode. Representative analog TM2 shows potent inhibition of TEAD auto-palmitoylation both in vitro and in cells. Surprisingly, the co-crystal structure of the human TEAD2 YAP-binding domain (YBD) in complex with TM2 reveals that TM2 adopts an unexpected binding mode by occupying not only the hydrophobic PBP, but also a new side binding pocket formed by hydrophilic residues. RNA-seq analysis shows that TM2 potently and specifically suppresses TEAD-YAP transcriptional activities. Consistently, TM2 exhibits strong anti-proliferation effects as a single agent or in combination with a MEK inhibitor in YAP-dependent cancer cells. These findings establish TM2 as a promising small molecule inhibitor against TEAD-YAP activities and provide new insights for designing novel TEAD inhibitors with enhanced selectivity and potency.
Anterior insular cortex firing links initial and sustained encoding during aversion-resistant alcohol consumption
Authors: Starski Phillip , Morningstar Mitch , Katner Simon , Frasier Raizel , De Oliveira Sergio Thatiane , Wean Sarah , Lapish Christopher , Hopf F Woodward
Published: May 2022

Compulsive-like alcohol drinking (CLAD), where intake persists despite adverse consequences, is often a core facet of alcohol use disorder. Recent work sheds light on underlying mechanisms, but much remains unknown about CLAD etiology. Previously, we showed that projections from anterior insula (aINS), a central mediator of emotion, motivation, and interoception, promote CLAD in rodents, and heavy human drinkers exhibit similar insula-circuit recruitment under compulsion-like conditions. However, global aINS inhibition also reduces alcohol-only drinking (AOD), and one major obstacle is the lack of information on aINS firing patterns that could promote different aspects of intake. Here, we recorded single-unit activity in right aINS from 15 rats during AOD or CLAD (10mg/L or 60mg/L quinine in alcohol). Neurons with a sustained-increase or sustained-decrease phenotype (SIP, SDP) showed no firing differences across drinking conditions. In contrast, aINS neurons with a phenotype of strong firing increase at initiation of responding (IRP) showed significantly greater activity across the rest of licking during CLAD versus AOD, concurring with our previous behavioral findings suggesting quick evaluation and response strategy adjustment under CLAD. There were also no condition-related differences in firing-phenotype abundance. Further, total responding only correlated with abundance of SDP cells, but SDP firing returned to baseline during pauses in licking, while IRP and SIP sustained responding through pauses in licking. Thus, only aINS cells with a particular strong firing at licking onset showd greater sustained responding under compulsion-like conditions, while other cells likely promoted drinking more generally, providing critical new information about how aINS activity could promote alcohol consumption under different drinking conditions.
Topoisomerase I promotes formation of a novel DNA intermediate in the ribosomal DNA
Authors: Molinar Temistocles , Sultanov Daniel , Klein Hannah , Hochwagen Andreas
Published: May 2022

The ribosomal DNA (rDNA) is a conserved but highly unstable multi-gene locus that codes for the RNA components of the ribosome (rRNA). Despite being essential for protein translation and survival, rRNA gene-copy numbers fluctuate frequently. Here, we describe a novel rDNA intermediate that may be involved in these copy-number changes in Saccharomyces cerevisiae. Two-dimensional gel analyses revealed a structure that includes a large single-stranded tail and arises from the promoter of the 35S rRNA gene. Formation of this intermediate is unaffected by reduced 35S transcription but relies on topoisomerase I (Top1). Unexpectedly, intermediate formation is also independent of S phase or the rDNA-instability factor Fob1, even though Fob1 is mediates the major peak of Top1 cleavage complexes in the rDNA. Indeed, we find that the known rDNA instability phenotypes of top1 mutants, including increased formation of extrachromosomal rDNA circles, elevated genetic marker loss, and instability of critically short rDNA arrays, are also largely independent of Fob1. We therefore speculate that failure to form this intermediate leads to rDNA instability in top1 mutants.
The structure of yeast Npl3 bound to RNA reveals a cooperative sequence-specific recognition and an RNA chaperone role in splicing
Authors: Moursy Ahmed , Cléry Antoine , Gerhardy Stefan , Betz Katharina M. , Rao Sanjana , Campagne Sébastien , Beusch Irene , Duszczyk Malgorzata M. , Robinson Mark D. , Panse Vikram Govind , Allain Frédéric H.-T.
Published: May 2022

The conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by the RNA Recognition Motifs (RRM1 & RRM2) of Npl3 during the splicing reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover the consensus sequence bound to each RRM. High-resolution NMR structures show that RRM2 recognizes a 5’-GNGG-3’ motif leading to an unusual mille-feuille topology. These structures also reveal how RRM1 preferentially interacts with a CC-dinucleotide upstream of this motif, and how the inter-RRM linker and the region C-terminal to RRM2 contributes to cooperative RNA-binding. Structure-guided functional studies show that Npl3 genetically interacts with U2 snRNP specific factors and we provide evidence that Npl3 melts U2 snRNA stem-loop I, a prerequisite for U2/U6 duplex formation within the catalytic center of the Bactspliceosomal complex. Thus, our findings provide insights into an unanticipated RNA chaperoning role for Npl3 during spliceosome active site formation.
Functional analysis in a model sea anemone reveals phylogenetic complexity and a role in cnidocyte discharge of DEG/ENaC ion channels
Authors: Aguilar-Camacho Jose Maria , Foreman Katharina , Aharoni Reuven , Gründer Stefan , Moran Yehu
Published: May 2022

Ion channels of the DEG/ENaC family share a similar structure but serve strikingly diverse biological functions, such as Na+ reabsorption, mechanosensing, proton-sensing, chemosensing and cell-cell communication via neuropeptides. This functional diversity raises the question of the ancient function of DEG/ENaCs. Using an extensive phylogenetic analysis across many different animal groups, we found a surprising diversity of DEG/ENaCs already in Cnidaria (corals, sea anemones, hyrdoids and jellyfish). Using a combination of gene expression analysis, electrophysiological and functional studies combined with pharmacological inhibition as well as genetic knockout in the model cnidarian Nematostella vectensis, we reveal an unanticipated role for a proton-sensitive DEG/ENaC in discharge of N. vectensis cnidocytes, the stinging cells typifying all cnidarians. Our study supports the view that DEG/ENaCs are versatile channels that have been co-opted for diverse functions since their early occurrence in animals and that respond to simple and ancient stimuli, such as omnipresent protons.

Teaser

The analysis of an ion channel class in a sea anemone reveals its role in acidity-induced discharge of stinging cells.
“Replication stalling activates SSB for recruitment of DNA damage tolerance factors”
Authors: Thrall Elizabeth S. , Piatt Sadie C. , Chang Seungwoo , Loparo Joseph J.
Published: May 2022

Translesion synthesis (TLS) polymerases bypass DNA lesions that block replicative polymerases, allowing cells to tolerate DNA damage encountered during replication. It is well known that most bacterial TLS polymerases must interact with the sliding clamp processivity factor to carry out TLS, but recent work in Escherichia coli has revealed that single-stranded DNA-binding protein (SSB) plays a key role in enriching the TLS polymerase Pol IV at stalled replication forks in the presence of DNA damage. It remains unclear how this interaction with SSB enriches Pol IV in a stalling-dependent manner given that SSB is always present at the replication fork. In this study we use single-molecule imaging in live E. coli cells to investigate this SSB-dependent enrichment of Pol IV. We find that Pol IV is enriched through its interaction with SSB in response to a range of different replication stresses, and that changes in SSB dynamics at stalled forks may explain this conditional Pol IV enrichment. Finally, we show that other SSB-interacting proteins (SIPs) are likewise selectively enriched in response to replication perturbations, suggesting that this mechanism is likely a general one for enrichment of repair factors near stalled replication forks.
Disruption of integrin alpha-5/beta-1-dependent transforming growth factor beta-1 signaling pathway attenuates vessel co-option in colorectal cancer liver metastases
Authors: Rada Miran , Kapelanski-Lamoureux Audrey , Zlotnik Oran , Petrillo Stephanie , Lazaris Anthoula , Metrakos Peter
Published: May 2022

Colorectal cancer liver metastases (CRCLM) have two major histopathological growth patterns (HGPs) including angiogenic desmoplastic HGP (DHGP) and non-angiogenic replacement HGP (RHGP). The RHGP lesions obtain their blood supply through vessel co-option, where the cancer cells hijack the pre-existing blood vessels of the surrounding liver tissue. Consequently, anti-angiogenic therapies are less efficacious in CRCLM patients with RHGP lesions. Recently, we identified a positive correlation between the expression of Angiopoietin1 (Ang1) and the development of vessel co-opted CRCLM lesions in vivo. However, the mechanisms underlying Ang1 upregulation in vessel co-opting CRCLM lesions are unclear. Herein, we demonstrated that transforming growth factor β1 (TGFβ1) modulates the expression of Ang1 in hepatocytes in vitro. Significantly, pharmaceutical inhibition of integrin alpha-5/beta-1 (ITGα5β1) through ATN-161 impaired TGFβ1-dependent Ang1 expression in vitro and in vivo. Moreover, blocking ITGα5β1 attenuated the formation of vessel co-opting lesions. Furthermore, treatment with ATN-161 significantly improved survival in tumour-bearing mice. Taken together, our results suggest the molecular mechanism of Ang1 upregulation in vessel co-opting CRCLM and targeting this pathway may serve as promising therapeutic strategy to overcome the development of vessel co-option in CRCLM.
Cell walls are dynamically O-acetylated in the green seaweed, Ulva compressa
Authors: Bothwell John H. , Goodridge Alexander J. , Rapin Marie , Brennan Patrick J. , López Alexandra Traslaviña , Agrawal Akanksha , Fry Stephen C. , Campbell Georgia , Blomme Jonas
Published: May 2022

We report that cell wall polymers in the chlorophyte algae may be modified by O-acetylation. The importance of cell wall modifications in the green algae is not well understood, although similar modifications play key roles in land plants by modulating the properties of cell wall carbohydrate polymers. Using a combination of biophysical (Fourier-transform infrared and cross-polarisation heteronuclear correlation nuclear magnetic resonance spectroscopy), biochemical (thin-layer chromatography) and molecular approaches (yellow fluorescent protein-tagged transgene localisation), we show that the extractable ulvan fractions of Ulva compressa cell walls contain O-acetyl sidechains, we demonstrate that acetylation is dynamic and decreases reversibly in response to metal-induced stress, we note interactions between acetyl and borate sidechains and we locate two candidate genes that, together, may encode an acetyltransferase. We therefore propose that O-acetylation of ulvan residues is involved in the normal cell wall physiology of at least some chlorophyte algae. To the best of our knowledge, this is the first demonstration of O-acetyl sidechains in green algal cell wall polymers, and of reversible changes in algal cell wall polymer modification in response to stress.
Par3/Bazooka binds NICD and promotes Notch signalling duringDrosophiladevelopment
Authors: Wu Jun , Tannan Neeta Bala , Vuong Linh T. , Koca Yildiz , Collu Giovanna M. , Mlodzik Marek
Published: May 2022

The conservedbazooka (baz/par3) gene acts as a key regulator of asymmetrical cell divisions across the animal kingdom. Associated Par3/Baz-Par6-aPKC protein complexes are also well known for their role in the establishment of apical/basal cell polarity in epithelial cells. Here we define a novel, positive function of Baz/Par3 in the Notch pathway. UsingDrosophilawing and eye development, we demonstrate that Baz is required for Notch signaling activity and optimal transcriptional activation of Notch target genes. Baz appears to act independently of aPKC in these contexts, as knockdown ofaPKCdoes not causeNotchloss-of-function phenotypes. Using transgenic Notch constructs, our data positions Baz activity downstream of activating Notch cleavage steps and upstream of Su(H)/CSL transcription factor complex activity on Notch target genes. We demonstrate a biochemical interaction between NICD and Baz, suggesting that Baz is required for NICD activity before NICD binds to Su(H). Taken together, our data define a novel role of the polarity protein Baz/Par3, as a positive and direct regulator of Notch signaling through its interaction with NICD.
Loss-of-function mutation in humanOxidation Resistance gene 1disrupts the spatial-temporal regulation of histone arginine methylation in early brain development
Authors: Lin Xiaolin , Wang Wei , Yang Mingyi , Damseh Nadirah , de Sousa Mirta Mittelstedt Leal , Jacob Fadi , Lång Anna , Kristiansen Elise , Pannone Marco , Kissova Miroslava , Almaas Runar , Kuśnierczyk Anna , Siller Richard , Shahrour Maher , Al-Ashhab Motee , Abu-Libdeh Bassam , Tang Wannan , Slupphaug Geir , Elpeleg Orly , Bøe Stig Ove , Eide Lars , Sullivan Gareth J , Rinholm Johanne Egge , Song Hongjun , Ming Guo-li , van Loon Barbara , Edvardson Simon , Ye Jing , Bjørås Magnar
Published: May 2022

We report a loss-of-function mutation in the TLDc domain of humanOxidation Resistance 1(OXR1) gene, resulting in early-onset epilepsy, developmental delay, cognitive disabilities, and cerebellar atrophy. Patient lymphoblasts show impaired cell survival, proliferation, and hypersensitivity to oxidative stress. These phenotypes are rescued by TLDc domain replacement. We generated patient derived induced pluripotent stem cells (iPSCs) revealing impaired neural differentiation along with dysregulation of genes essential for neurodevelopment. We identified that OXR1 influences histone arginine methylation by activating protein arginine methyltransferases (PRMTs), suggesting OXR1 dependent mechanisms regulating gene expression during neurodevelopment. We modeled the function of OXR1 in early human brain development using patient derived brain organoids revealing that OXR1 contributes to the spatial-temporal regulation of histone arginine methylation in specific brain regions. Our work provides new insights into pathological features and molecular underpinnings associated with OXR1 deficiency, highlighting the therapeutic potential of OXR1 in numerous neurodegenerative and neurodevelopmental disorders.
Open science resources from the Tara Pacific expedition across coral reef and surface ocean ecosystems
Authors: Lombard Fabien , Bourdin Guillaume , Pesant Stéphane , Agostini Sylvain , Baudena Alberto , Boissin Emilie , Cassar Nicolas , Clampitt Megan , Conan Pascal , Silva Ophélie Da , Dimier Céline , Douville Eric , Elineau Amanda , Fin Jonathan , Flores J. Michel , Ghiglione Jean François , Hume Benjamin C.C. , Jalabert Laetitia , John Seth G. , Kelly Rachel L. , Koren Ilan , Lin Yajuan , Marie Dominique , McMinds Ryan , Mériguet Zoé , Metzl Nicolas , Paz-García David A. , Pedrotti Maria Luiza , Poulain Julie , Pujo-Pay Mireille , Ras Joséphine , Reverdin Gilles , Romac Sarah , Rouan Alice , Röttinger Eric , Vardi Assaf , Voolstra Christian R. , Moulin Clémentine , Iwankow Guillaume , Banaigs Bernard , Bowler Chris , de Vargas Colomban , Forcioli Didier , Furla Paola , Galand Pierre E. , Gilson Eric , Reynaud Stéphanie , Sunagawa Shinichi , Sullivan Matthew B. , Thomas Olivier , Troublé Romain , Thurber Rebecca Vega , Wincker Patrick , Zoccola Didier , Allemand Denis , Planes Serge , Boss Emmanuel , Gorsky Gaby
Published: May 2022

Abstract

The Tara Pacific expedition (2016-2018) sampled coral ecosystems around 32 islands in the Pacific Ocean and the ocean surface waters at 249 locations, resulting in the collection of nearly 58,000 samples. The expedition was designed to systematically study warm coral reefs and included the collection of corals, fish, plankton, and seawater samples for advanced biogeochemical, molecular, and imaging analysis. Here we provide a complete description of the sampling methodology, and we explain how to explore and access the different datasets generated by the expedition. Environmental context data were obtained from taxonomic registries, gazetteers, almanacs, climatologies, operational biogeochemical models, and satellite observations. The quality of the different environmental measures has been validated not only by various quality control steps but also through a global analysis allowing the comparison with known environmental large-scale structures. Such a wide released datasets opens the perspective to address a wide range of scientific questions.
Relations outside the workplace matter! A nexus of coworker ostracism, relational capital, alternate belongingness and knowledge hiding
Authors: Fatima Tehreem , Bilal Ahmad Raza , Imran Muhammad Kashif , Waqas Muhammad
Published: May 2022

Purpose

The current study aims to investigate the impact of coworker ostracism on coworker-directed knowledge hiding through the mediating role of relational social capital and moderating role of alternate belongingness in Pakistani higher educational settings.

Design/methodology/approach

A time-lagged study was carried out in which data from teaching and non-teaching faculty (N= 217) from the higher education sector of Lahore, Pakistan, were collected through multi-stage sampling. The collected data were analysed using moderated mediation analysis (PROCESS model 4 and 7).

Findings

The results revealed that ostracism from coworkers has an unfavourable impact on relational social capital that in turn promotes knowledge hiding. Nonetheless, if ostracized employees had sources to fulfil belongingness needs outside the work settings, this negative association was strengthened.

Originality/value

The authors have taken the role of belongingness outside the workplace in explaining the coworker ostracism and knowledge hiding relationship in higher educational settings and identified the explanatory role of relational social capital.
Supply chains and the success of M&As: investigating the effect of structural equivalence of merging firms' supplier and customer bases
Authors: Chae Sangho , Son Byung-Gak , Yan Tingting , Yang Yang S.
Published: May 2022

Purpose

This study investigates the extent to which structural equivalence between acquiring and target firms is associated with post-merger and acquisition (M&A) performance—a relationship that is proposed to be moderated by industry-level vertical relatedness between acquiring and target firms.

Design/methodology/approach

Applying social network analysis and regression, this study analyzes a buyer–supplier relationship network dataset of 279 M&A deals completed between 2010 and 2017 to test the hypotheses. Structural equivalence is measured as the proportion of common customers and suppliers between an acquiring firm and a target firm.

Findings

Supporting a view about the importance of supply chains in explaining M&As outcomes, the results suggest that the structural equivalence in the supplier network is positively associated with post-M&A firm performance. The results also show that the effect of the structural equivalence in the customer network is moderated by vertical relatedness between two merging firms (i.e. structural equivalence contributes to post-M&A performance when vertical industry relatedness is high).

Originality/value

This study contributes to the M&A and supply network literature by investigating the performance implications of structural equivalence in supplier and customer networks, demonstrating the importance of taking a supply chain view when explaining M&As outcomes. Specifically, the authors suggest considering structural equivalence as a new type of relatedness between merging firms (i.e. relatedness in network resources in explaining post-M&A performance). It also indicates how industry-level vertical resource relatedness, which is about relatedness in internal resources between the two firms, could interact with firm-level network resource relatedness, which is about relatedness in external supply chain resources between the two firms, in affecting post-M&A performance.
Guidelines for public sector managers on assessing the impact of outsourcing on business continuity strategies: a Brazilian case
Authors: Aragão João Paulo Santos , Fontana Marcele Elisa
Published: May 2022

Purpose

This paper aims to propose guidelines for public sector managers in assessing the impact of outsourcing on business continuity (BC) strategies. This paper evaluated how public managers from the state of Pernambuco, Brazil, perceive outsourcing, considering BC and how it relates to the outsourcing of services and activities.

Design/methodology/approach

Theoretical lenses of outsourcing and BC were used to derive the study hypotheses. A questionnaire was drawn up to collect information to test the hypotheses. To test the proposed hypotheses, binary logistic regression was used through an empirical analysis of a sample of 51 Brazilian public managers.

Findings

This study found that when the public sector suffers from negative impacts of financial restrictions, outsourced services are the first ones to receive the negative impacts. This has had an adverse impact on BC in the public sphere. On the other hand, the authors verified that the public sphere’s capacity for resilience and the existence of specific methodologies to support public managers in outsourcing decision-making can contribute to BC.

Research limitations/implications

This study assists public organizations to take advantage of internal outsourced services in the best possible way, making better use of public resources, gaining social legitimacy and legitimacy also in the provision of public services. However, each public sector can present different risks of non-continuity, and this aspect could not be considered in this research as well.

Originality/value

This study is a pioneer in highlighting the relationships between outsourcing strategies and BC in public services in Brazil. Through the guidelines discussed in this study, public managers could develop a more effective response to the implications of post-outsourcing budget constraints. In addition, the findings of this paper add to an understanding of the importance of business strategies for public services continuity and seek to help reduce uncertainties and better inform the government decision-making process.
The mediating effects of psychological states on the relationship of job dimensions to personal and work outcomes, for fresh graduates
Authors: Serhan Carole , Tsangari Haritini
Published: May 2022

Purpose

In today's challenging markets, organizations need to explore new ways to maximize employees' effectiveness and job satisfaction. Within this context, employed fresh graduates are a special group, which requires attention. Recognizing its needs in job design is one of the keys. The aim of the study is to determine the mediating role of experienced psychological states in the relationship between job dimensions and personal/work outcomes (motivation, satisfaction, effectiveness and commitment).

Design/methodology/approach

The new “modified job characteristics model” (MJCM) was implemented, where the focus was on testing if experienced psychological states play a mediating role. An index for summarizing core job dimensions (modified motivating potential score (MMPS)) was also developed in the study. For the empirical testing of the new modeling framework, a sample of 630 employed fresh graduates in Lebanon was selected. Various statistical analyses were performed, including partial correlation and multiple regression analysis.

Findings

Results showed that for those core job dimensions that significantly affected fresh graduates' personal/work outcomes, the relation was not direct causal, but was mediated by “experienced meaningfulness of the work”, “experienced responsibility for outcomes of the work”, “knowledge of results”, “self-confidence” and “prestige inside outside”. Further, MMPS was verified as a valid score reflecting the “motivating potential” of a job.

Practical implications

The findings demonstrate the importance of effectively designing and redesigning jobs: employers should focus on the core job dimensions and adopt an adjusted strategy to enhance fresh graduates' affective and behavioral responses.

Originality/value

The current study innovatively examines fresh graduates' psychological states and their role as a mediator in the relation between job dimensions and job satisfaction or commitment. A new modeling framework is used and an index for summarizing job dimensions is developed.
Residual stresses in additively manufactured parts: predictive simulation and experimental verification
Authors: Shaikh Mohammad Qasim , Berfield Thomas A. , Atre Sundar V.
Published: May 2022

Purpose

The purpose of this paper is to investigate a simulation solution for estimating the residual stresses developed in metal fused filament fabrication (MF3) printed parts. Additionally, to verify these estimates, a coupled experimental–computational approach using the crack-compliance method was investigated in this study.

Design/methodology/approach

In this study, a previously validated thermomechanical process simulation was used to estimate the residual stresses developed in the MF3 printing process. Metal-filled polymer filament with a solids loading of 59 Vol.% Ti-6Al-4V was studied. For experimental validation of simulation predictions, the MF3 printed green parts were slitted incrementally and the corresponding strains were measured locally using strain gauges. The developed strain was modeled in finite-element-based structural simulations to estimate a compliance matrix that was combined with strain gauge measurements to calculate the residual stresses. Finally, the simulation results were compared with the experimental findings.

Findings

The simulation predictions were corroborated by the experimental results. Both results showed the same distribution pattern, that is, tensile stresses at the outer zone and compressive stresses in the interior. In the experiments, the residual stresses varied between 1.02 MPa (tension) and −2.28 MPa (compression), whereas the simulations were predicted between 1.37 MPa (tension) and −1.39 MPa (compression). Overall, there was a good quantitative agreement between the process simulation predictions and the experimental measurements, although there were some discrepancies. It was concluded that the thermomechanical process simulation was able to predict the residual stresses developed in MF3 printed parts. This validation enables the printing process simulation to be used for optimizing the part design and printing parameters to minimize the residual stresses.

Originality/value

The applicability of thermomechanical process simulation to predict residual stresses in MF3 printing is demonstrated. Additionally, a coupled experimental–computational approach using the crack-compliance method was used to experimentally determine residual stresses in the three-dimensional printed part to validate the simulation predictions. Moreover, this paper presents a methodology that can be used to predict and measure residual stresses in other additive manufacturing processes, in general, though MF3 was used as demonstrator in this work.
Trends in over the top (OTT) research: a bibliometric analysis
Authors: Singh Navjit , Arora Simran , Kapur Bharti
Published: May 2022

Purpose

The purpose of this paper is to examine current trends in over the top (OTT) research through bibliometric analysis of Scopus and Web of Science indexed publications. This study attempted to identify the thrust areas that may be addressed through future research initiatives.

Design/methodology/approach

This study included bibliometric analysis of research articles published on OTT domain for a time period ranging from 2011 to 2021. The authors were able to extract 137 unique articles from selected databases with inclusion criteria limited to social sciences only. The retrieved data is then analyzed using the R studio and VoSviewer user interfaces. Finally, discussions on citations, keywords, authors and source contributions toward the development of field were presented using descriptive and visual displays.

Findings

OTT as a research theme has gained wider acceptance recently. However, there is a scarcity of studies on the subject. The authors discovered that previous studies in the field had focused on technological aspects of the domain thus leaving a plethora of opportunities for future researchers to explore. In this regard, the findings enlisted few unexplored domains specific to OTT that require immediate attention of the researchers and stakeholders. It was suggested to investigate the field from marketing, behavioral, regulatory, social and quality aspects so as to broaden its scope.

Originality/value

To the best of the authors’ knowledge, this is going to be the first bibliometric study ever conducted on OTT research. This study may be considered unique in identifying current trends in OTT research and recommending a course of action for future researchers.
THEORY FROM EMPTY LAND: Informal Commoning Outside/Within Economies and Ecologies of the Urban
Authors: Roast Asa
Published: May 2022

Debates over the ontology of contemporary urbanization have questioned the notion of a meaningful ‘outside’ to the urban and have called for greater attention to the socially contested construction of urban subjects and space. Ethnographic study of informal peri‐urban agriculture in the rapidly urbanizing city of Chongqing in Southwest China allows for a critical examination of the everyday ecologies and economies of planetary urbanization. The state‐led expansion of Chongqing since the early 2000s has created a peri‐urban zone consisting of large areas of undeveloped land awaiting construction, which is utilized informally by displaced ‘urbanized’ peasants and migrant workers. The use of this ‘empty’ urban land for agriculture reveals informal practices and displaced subjects which are variously positioned as ‘outside’ or ‘within’ urban systems and values. The undeveloped land remains ecologically entangled with urban processes and is the site of a contested commoning of space which is regarded as external to urban market values. Theorizing from the kongdi (empty land) launches a novel understanding of under‐studied urbanizing spaces which are positioned ambiguously outside urban governance, are under threat of rapid enclosure within urban regimes of accumulation, and spatialize the negotiation of the boundaries and meaning of the urban itself.
Potential missed opportunities for antenatal corticosteroid exposure and outcomes among periviable births: Observational cohort study
Authors: Travers Colm P. , Hansen Nellie I. , Das Abhik , Rysavy Matthew A. , Bell Edward F. , Ambalavanan Namasivayam , Peralta‐Carcelen Myriam , Tita Alan T. , Van Meurs Krisa P. , Carlo Waldemar A. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Published: May 2022

Objective

To test the hypothesis that potential missed opportunities for antenatal corticosteroids increase as gestational age decreases and are associated with adverse outcomes.

Design

Observational cohort study.

Setting

Twenty‐four US centers in the Neonatal Research Network.

Population

Actively treated infants at 22–25 weeks of gestation and with birthweight 401–1000 g, without major birth defects, born 2006–18.

Methods

Potential missed opportunity was defined as no antenatal corticosteroids but did have prenatal antibiotics, and/or magnesium sulphate, and/or prolonged rupture of membranes. Poisson regression models adjusted for baseline characteristics.

Main outcome measures

Antenatal corticosteroid exposure, mortality and severe intracranial haemorrhage or periventricular leucomalacia.

Results

A total of 6966 (87.5%) infants were exposed to antenatal corticosteroids, 454 (5.7%) had no exposure but potential missed opportunities for antenatal corticosteroid exposure, and 537 (6.7%) had no exposure and no evidence of potential missed opportunities. Compared with infants born at 25 weeks, potential missed opportunities for antenatal corticosteroid exposure were more likely at 22 weeks (adjusted relative risk [aRR] 11.06, 95% confidence interval [CI] 7.52–16.27) and 23 weeks (aRR 3.24, 95% CI 2.44–4.29) but did not differ at 24 weeks (aRR 1.08, 95% CI 0.82–1.42). Potential missed opportunities for antenatal corticosteroids decreased over time at 22–23 weeks of gestation. Antenatal‐corticosteroid‐exposed infants had lower risk of death (31.0% versus 54.8%; aRR 0.77, 95% CI 0.70–0.84) and survivors had lower risk of severe brain injury (25.0% versus 44.5%; aRR 0.64, 95% CI 0.55–0.73) compared with infants with potential missed opportunities.

Conclusion

Potential missed opportunities for antenatal corticosteroid exposure increased with decreasing gestational age and were associated with higher rates of death and severe brain injury among actively treated periviable births.
Personalised pre‐eclampsia prevention—Are we a step further?
Authors: Fields Neville J. , Wang Rui , Palmer Kirsten R.
Published: May 2022

Linked article: This is a mini commentary on Kinshella et al., pp. 1833–1843 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17222
Making the Invisible Visible
Authors: Tarran Brian
Published: May 2022

Geographer James Cheshire talks about his latest book – an atlas that sets out to reveal “the invisible patterns that shape our lives”
Unanswered Questions in the p-value Debate
Authors: Hirschauer Norbert
Published: May 2022

A statement on p-values and statistical significance by the ASA president's task force fails to tackle two crucial questions, says Norbert Hirschauer