bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternating Magnetic Fields Drive Stimulation of Gene Expression via Generation of Reactive Oxygen Species
Authors: Mundell Jordan W. , Brier Matthew I. , Orloff Everest , Stanley Sarah A. , Dordick Jonathan S.
Published: September 2023

Magnetogenetics represents a method for remote control of cellular function. Despite successful use of magnetic fields to control gene expressionin vitroandin vivo, the mechanism underlying magnetogenetics is largely unknown, thereby hindering further development and applications. Previous work suggests a chemical-based mechanism involving the generation of reactive oxygen species (ROS) as a platform initiator and downstream signaling molecule. Herein, a chemical biology approach was used to elucidate further the mechanism of radio frequency-alternating magnetic field (RF-AMF) stimulation of a TRPV1-ferritin magnetogenetics platform that leads to Ca2+gating. RF-AMF stimulation of HEK 293T cells expressing TRPV1-Ferritin resulted in a ∼30% and ∼140% increase in intra- and extracellular ROS levels, respectively. Mutations to specific cysteine residues in TRPV1 responsible for ROS sensitivity eliminated RF-AMF driven Ca2+-dependent transcription of secreted embryonic alkaline phosphatase (SEAP). Using a non-tethered (to TRPV1) ferritin also eliminated RF-AMF driven SEAP production. These results suggest ferritin-dependent ROS activation of TRPV1 plays a key role in the initiation of magnetogenetics. Furthermore, inhibition of IP3R-based endoplasmic reticulum (ER) Ca2+release with Xestospongin C, inhibition of protein kinase C (PKC) activity with Gö 6983, or inhibition of NADPH oxidase (NOX) isoforms 1/2 gp91phoxcytochrome with GSK 2795039 eliminated short-term RF-AMF potentiation of SEAP production with capsaicin. Similarly, Gö 6983 significantly reduced long-term RF-AMF capsaicin potentiation of SEAP production. These results suggest that ROS-activated TRPV1 signaling to increase intracellular Ca2+includes pathways involving PKC, NOX, and the ER. Together, these findings fill in current knowledge gaps in the mechanism of magnetogenetics, which may lead to translational applications in medicine and biotechnology.
Immunogenicity and efficacy of a subcutaneously administered, adjuvanted vaccine containing modified S1 spike protein of SARS-CoV-2 variant C.1.2
Authors: Bowe Michael , Wright Emily , Pushko Peter , Backstedt Brian , Gardner Casey , Short-Freeman Micah , Kar Swagata , Wright David Craig
Published: September 2023

During the COVID-19 pandemic, vaccines have produced protective immunity sufficient enough to cause a decrease in hospitalizations and deaths; however, the pandemic continues due to mutational events, predominantly occurring in the S1 sequence of the spike protein of SARS-CoV-2. We have developed a baculovirus-expressed, modified S1 SARS-CoV-2 protein based on the C.1.2 variant, which was first identified in South Africa.1This was encapsulated in a vitamin E containing, nonphospholipid liposome, which was then used to subcutaneously immunize Syrian hamsters. This vaccine, when administered at day 1 generates IgG responses that react to the modified C.1.2 S1 protein; full-length spike proteins from Wuhan-Hu-1, Delta, Omicron BA.1; and the Omicron recombinant variant XBB.1.5 in 100% of the animals. The second dose administered subcutaneously on day 28 demonstrated anamnestic response in the quantitative IgG assay to the Wuhan-Hu-1 spike Receptor Binding Domain (RBD). In addition, antibody IgA and IgM responses in sera were demonstrated. Serum IgG antibody responses to the spike proteins of the modified C.1.2 S1 and full-length spike proteins Wuhan-Hu-1, Delta, Omicron BA.1, and Omicron recombinant XBB.1.5 variants are elevated for over 120 days. Challenge of vaccinated and unvaccinated hamsters at day 126 of the study with an Omicron BA.1 resulted in a difference in weight change and viral load based on the qRT-PCR assay seven days after challenge.
Soil Prokaryotic and Fungal Biome Structures Associated with Crop Disease Status across the Japan Archipelago
Authors: Fujita Hiroaki , Yoshida Shigenobu , Suzuki Kenta , Toju Hirokazu
Published: September 2023

Archaea, bacteria, and fungi in the soil are increasingly recognized as determinants of agricultural productivity and sustainability. A crucial step for exploring soil microbiomes with high ecosystem functions is to perform statistical analyses on potential relationship between microbiome structure and functions based on comparisons of hundreds or thousands of environmental samples collected across broad geographic ranges. In this study, we integrated agricultural field metadata with microbial community analyses by targeting > 2,000 soil samples collected along a latitudinal gradient from cool-temperate to subtropical regions in Japan (26.1– 42.8 °N). The data involving 632 archaeal, 26,868 bacterial, and 4,889 fungal operational taxonomic units detected across the fields of 19 crop plant species allowed us to conduct statistical analyses (permutational analyses of variance, generalized linear mixed models, and randomization analyses) on relationship among edaphic factors, microbiome compositions, and crop disease prevalence. We then examined whether the diverse microbes form species sets varying in potential ecological impacts on crop plants. A network analysis suggested that the observed prokaryotes and fungi were actually classified into several species sets (network modules), which differed substantially in associations with crop disease prevalence. Within the network of microbe-to-microbe coexistence, ecologically diverse microbes, such as an ammonium-oxidizing archaeum, an antibiotics-producing bacterium, and a potentially mycoparasitic fungus, were inferred to play key roles in shifts between crop-disease-promotive and crop-disease-suppressive states of soil microbiomes. The bird’s-eye view of soil microbiome structure will provide a basis for designing and managing agroecosystems with high disease-suppressive functions.

IMPORTANCE

Understanding how microbiome structure and functions are organized in soil ecosystems is one of the major challenges in both basic ecology and applied microbiology. Given the ongoing worldwide degradation of agroecosystems, building frameworks for exploring structural diversity and functional profiles of soil microbiomes is an essential task. Our study provides an overview of cropland microbiome states in light of potential crop-disease-suppressive functions. The large dataset allowed us to explore highly functional species sets that may be stably managed in agroecosystems. Furthermore, an analysis of network architecture highlighted species that are potentially used to cause shifts from disease-prevalent states of agroecosystems to disease-suppressive states. By extending the approach of comparative analyses towards broader geographic ranges and diverse agricultural practices, agroecosystem with maximized biological functions will be further explored.
Protein Kinase Structure and Dynamics: Role of the αC-β4 Loop
Authors: Wu Jian , Jonniya Nisha A. , Hirakis Sophia P. , Olivieri Cristina , Veglia Gianluigi , Kornev Alexandr P. , Taylor Susan S.
Published: September 2023

Although the αC-β4 loop is a stable feature of all protein kinases, the importance of this motif as a conserved element of secondary structure, as well as its links to the hydrophobic architecture of the kinase core, has been underappreciated. We first review the motif and then describe how it is linked to the hydrophobic spine architecture of the kinase core, which we first discovered using a computational tool, Local Spatial Pattern (LSP) alignment. Based on NMR predictions that a mutation in this motif abolishes the synergistic high-affinity binding of ATP and a pseudo substrate inhibitor, we used LSP to interrogate the F100A mutant. This comparison highlights the importance of the αC-β4 loop and key residues at the interface between the N- and C-lobes. In addition, we delved more deeply into the structure of the apo C-subunit, which lacks ATP. While apo C-subunit showed no significant changes in backbone dynamics of the αC-β4 loop, we found significant differences in the side chain dynamics of K105. The LSP analysis suggests disruption of communication between the N- and C-lobes in the F100A mutant, which would be consistent with the structural changes predicted by the NMR spectroscopy.
Expression of mRNAs Encoding Hypothalamic Small Proteins, Neurosecretory Protein GL and Neurosecretory Protein GM, in the Japanese Quail,Coturnix japonica
Authors: Kato Masaki , Iwakoshi-Ukena Eiko , Narimatsu Yuki , Furumitsu Megumi , Ukena Kazuyoshi
Published: September 2023

Neurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM) are novel neuropeptides that have been discovered in the hypothalamic infundibulum of chickens. NPGL and NPGM play important roles in lipid metabolism in juvenile chickens. The physiological functions of NPGL and NPGM in sexually mature birds remain unknown. The Japanese quail (Coturnix japonica) seems to be an appropriate model for analyzing NPGL and NPGM during sexual maturity. However, studies on NPGL or NPGM have yet to be reported in the Japanese quail. In the present study, we identified cDNAs encoding precursor proteins of NPGL and NPGM in the quail hypothalamus. In situ hybridization revealed thatNPGLmRNA-expressing cells in the hypothalamus were localized in the infundibular nucleus and median eminence, andNPGMmRNA-expressing cells were only found in the mammillary nucleus. Immunohistochemistry revealed that NPGM-like immunoreactive cells were distributed in the mammillary nucleus, whereas NPGL-like immunoreactive cells were not detected in the hypothalamus. Real-time PCR analysis indicated that the expression ofNPGLmRNA was higher in the hypothalamus of females than in males, andNPGMmRNA expression showed no sex differences.NPGLandNPGMmRNA expression in males was upregulated after 24 h of food deprivation. In females, onlyNPGMmRNA expression was increased by fasting. These results suggest that the physiological functions of NPGL and NPGM are different in quail, and these factors are involved in sex differences in energy metabolism.
Community ecology of phages on a clonal bacterial host
Authors: Pyenson Nora C. , Leeks Asher , Nweke Odera , Goldford Joshua E. , Turner Paul E. , Foster Kevin R. , Sanchez Alvaro
Published: September 2023

Bacteriophages are the most abundant and diverse biological entities on Earth, yet the ecological mechanisms that sustain this extraordinary diversity remain unclear. Here, we have discovered a general mechanism that allows phage diversity to outstrip the diversity of their bacterial hosts. We assembled and passaged dozens of diverse phage communities on a single, non-coevolving strain ofEscherichia coliuntil the phage communities reached equilibrium. In all cases, we found multiple phage species coexisted stably, despite competition for a single, clonal host population. Coexistence within these communities was supported through host phenotypic heterogeneity, whereby phages specialized on cells adopting different growth phenotypes. Our experiments reveal a rich community ecology of bacteriophages where multiple phage species coexist and interact at the scale of a single bacterial host.

One-Sentence Summary

Diverse communities of phages emerge stably and consistently on a clonal bacterial host, enabled by phenotypic heterogeneity.
AIRR-C Human IG Reference Sets: curated sets of immunoglobulin heavy and light chain germline genes
Authors: Collins Andrew M. , Ohlin Mats , Corcoran Martin , Heather James M. , Ralph Duncan , Law Mansun , Martínez-Barnetche Jesus , Ye Jian , Richardson Eve , Gibson William S. , Rodriguez Oscar L. , Peres Ayelet , Yaari Gur , Watson Corey T. , Lees William D.
Published: September 2023

Analysis of an individual’s immunoglobulin (IG) gene repertoire requires the use of high-quality germline gene Reference Sets. The Adaptive Immune Receptor Repertoire-Community (AIRR-C) Reference Sets have been developed to include only human IG heavy and light chain alleles that have been confirmed by evidence from multiple high-quality sources. By including only those alleles with a high level of support, including some new sequences that currently lack official names, AIRR-seq analysis will have greater accuracy and studies of the evolution of immunoglobulin genes, their allelic variants and the expressed immune repertoire will be facilitated. Although containing less than half the previously recognised IG alleles (e.g. just 198 IGHV sequences), the Reference Sets eliminated erroneous calls and provided excellent coverage when tested on a set of repertoires from 99 individuals comprising over 4 million V(D)J rearrangements. To improve AIRR-seq analysis, some alleles have been extended to deal with short 3’ or 5’ truncations that can lead them to be overlooked by alignment utilities. To avoid other challenges for analysis programs, exact paralogs (e.g. IGHV1-69*01 and IGHV1-69D*01) are only represented once in each set, though alternative sequence names are noted in accompanying metadata. The Reference Sets also include novel alleles: 8 IGHV alleles, 2 IGKV alleles and 5 IGLV alleles. The version-tracked AIRR-C Reference Sets are freely available at the OGRDB website (https://ogrdb.airr-community.org/germline_sets/Human) and will be regularly updated to include newly-observed and previously-reported sequences that can be confirmed by new high-quality data.
Equine dermatitis outbreak associated with parapoxvirus
Authors: Virtanen Jenni , Hautala Katja , Utriainen Mira , Dutra Lara , Eskola Katarina , Airas Niina , Uusitalo Ruut , Ahvenainen Ella , Smura Teemu , Sironen Tarja , Vapalahti Olli , Kant Ravi , Virtala Anna-Maija K. , Kinnunen Paula M.
Published: September 2023

Parapoxviruses (PPV) cause skin and mucous membrane lesions in several animal species, and of the five recognized PPVs, at least three are zoonotic. Equine PPV (EqPPV) is the sixth one initially described in humans in the United States and later in a severely sick horse in Finland in 2013–2015. In 2021–2022, a large-scale pustulo-vesicular pastern dermatitis outbreak occurred in horses all over Finland. This study aimed at analysing the outbreak, identifying and describing the causative agent, describing clinical signs, and searching for risk factors. EqPPV was identified as a probable causative agent and co-infections with several potentially pathogenic and zoonotic bacteria were observed. Histopathologically, suppurative and ulcerative dermatitis was diagnosed. Due to the lack of specific tests for this virus, we developed a novel diagnostic EqPPV-PCR with sensitivity of 10 copies/reaction. Based on a large proportion of the genome sequenced directly from clinical samples, very little variation was detected between the sequences of the case from 2013 and the cases from 2021–2022. Based on an epidemiological survey, the main risk factor for pastern dermatitis was having racehorses. Approximately one third of the horses at each affected stable got clinical dermatitis, manifesting as severe skin lesions. Skin lesions were also occasionally reported in humans, indicating potential zoonotic transmission. Case stables commonly reported attendance in race events before acquiring the disease. Survey also identified differences in practises between case and control stables. Taken together, these results enable a better preparedness, diagnostics, and guidelines for future outbreaks.
AP profiling resolves co-translational folding pathway and chaperone interactionsin vivo
Authors: Chen Xiuqi , Kaiser Christian M.
Published: September 2023

Natural proteins have evolved to fold robustly along specific pathways. Folding begins during synthesis, guided by interactions of the nascent protein with the ribosome and molecular chaperones. However, the timing and progression of co-translational folding remain largely elusive, in part because the process is difficult to measure in the natural environment of the cytosol. We developed a high-throughput method to quantify co-translational folding in live cells that we term Arrest Peptide profiling (AP profiling). We employed AP profiling to delineate co-translational folding for a set of GTPase domains with very similar structures, defining how topology shapes folding pathways. Genetic ablation of major nascent chain-binding chaperones resulted in localized folding changes that suggest how functional redundancies among chaperones are achieved by distinct interactions with the nascent protein. Collectively, our studies provide a window into cellular folding pathways of complex proteins and pave the way for systematic studies on nascent protein folding at unprecedented resolution and throughput.
Sirenian genomes illuminate the evolution of fully aquatic species within the mammalian superorder Afrotheria
Authors: Tian Ran , Zhang Yaolei , Kang Hui , Zhang Fan , Jin Zhihong , Wang Jiahao , Zhang Peijun , Zhou Xuming , Lanyon Janet M. , Sneath Helen L. , Woolford Lucy , Fan Guangyi , Li Songhai , Seim Inge
Published: September 2023

Sirenians of the diverse superorder Afrotheria were the first mammals to retransition from land to water and are the sole herbivorous marine mammals, but little is known about the underlying genomic changes. Here, we generated a chromosome-level dugong (Dugong dugon) genome. A comparison of our assembly and a recent West Indian manatee genome with other afrotherian genomes revealed possible molecular solutions to aquatic life by sirenians, including a shift in daily activity patterns (circadian clock) and tolerance to a high-iodine plant diet mediated through changes in the iodide transporter NIS (SLC5A5) and its co-transporters. Functionalin vitroassays confirmed that sirenian amino acid substitutions alter the properties of the circadian clock protein PER2 and NIS. Sirenians show evidence of convergent regression of integumentary system (skin and its appendages) genes with cetaceans, the only other fully aquatic mammal group. Our analysis also uncovered gene losses that may be maladaptive in a modern environment, including a candidate gene (KCNK18) for sirenian cold stress syndrome likely lost during their evolutionary shift in daily activity patterns. Finally, genomes from nine Australian locations and the functionally extinct Okinawan population confirm and date a genetic break on the Australian east coast and highlight the need for whole-genome resequencing data from small or isolated dugong populations worldwide for conservation and genetic management.
SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide
Authors: Larsson Johan , Hellstrand Ebba , Hammarström Per , Nyström Sofie
Published: September 2023

An increasing number of reports suggest an association between COVID-19 infection and initiation or acceleration of neurodegenerative diseases (NDs) including Alzheimer’s disease (AD) and Creutzfeldt-Jakob disease (CJD). Both these diseases and several other NDs are caused by conversion of human proteins into a misfolded, aggregated amyloid fibril state. The fibril formation process is self-perpetuating by seeded conversion from preformed fibril seeds. We recently described a plausible mechanism for amyloid fibril formation of SARS-CoV-2 spike protein. Spike-protein formed amyloid fibrils upon cleavage by neutrophil elastase, abundant in the inflammatory response to COVID-19 infection.

We here provide evidence of significant Spike-amyloid fibril seeded acceleration of amyloid formation of CJD associated human prion protein (HuPrP) using anin vitroconversion assay. By seeding the HuPrP conversion assay with otherin vitrogenerated disease associated amyloid fibrils we demonstrate that this is not a general effect but a specific feature of spike-amyloid fibrils. We also showed that the amyloid fibril formation of AD associated Aβ1-42 was accelerated by Spike-amyloid fibril seeds. Of seven different 20-amino acid long peptides, Spike532 (532NLVKNKCVNFNFNGLTGTGV551) was most efficient in seeding HuPrP and Spike601 (601GTNTSNQVAVLYQDVNCTEV620) was most effective in seeding Aβ1-42, suggesting substrate dependent selectivity of the cross-seeding activity.

Albeit purelyin vitro, our data suggest that cross-seeding by Spike-amyloid fibrils can be implicated in the increasing number of reports of CJD, AD, and possibly other NDs in the wake of COVID-19.
On the estimation of genome-average recombination rates
Authors: Dutheil Julien Y.
Published: September 2023

The rate at which recombination events occur in a population is an indicator of its effective population size and the organism’s reproduction mode. It determines the extent of linkage disequilibrium along the genome and, thereby, the efficacy of both purifying and positive selection. The population recombination rate can be inferred using models of genome evolution in populations. Classical methods based on the patterns of linkage-disequilibrium provide the most accurate estimates, providing large sample sizes are used and the demography of the population is properly accounted for. Here, the capacity of approaches based on the sequentially Markov coalescent (SMC) to infer the genome-average recombination rate from as little as a single diploid genome is examined. SMC approaches provide highly accurate estimates even in the presence of changing population sizes, providing that (1) within genome heterogeneity is accounted for and (2) classical maximum-likelihood optimization algorithms are employed to fit the model. SMC-based estimates proved sensitive to the presence of gene conversion, which leads to an overestimation of the recombination rate if conversion events are frequent. Conversely, methods based on the correlation of heterozygosity succeed in disentangling the rate of crossing over from that of gene conversion events, but only when the population size is constant and the recombination landscape homogeneous. These results call for a convergence of these two methods to obtain accurate and comparable estimates of recombination rates between populations.
Training-dependent gradients of timescales of neural dynamics in the primate prefrontal cortex and their contributions to working memory
Authors: Trepka Ethan , Spitmaan Mehran , Qi Xue-Lian , Constantinidis Christos , Soltani Alireza
Published: September 2023

Cortical neurons exhibit multiple timescales related to dynamics of spontaneous fluctuations (intrinsic timescales) and response to task events (seasonal timescales) in addition to selectivity to task-relevant signals. These timescales increase systematically across the cortical hierarchy, e.g., from parietal to prefrontal and cingulate cortex, pointing to their role in cortical computations. It is currently unknown whether these timescales depend on training in a specific task and/or are an inherent property of neurons, and whether more fine-grained hierarchies of timescales exist within specific cortical regions. To address these questions, we analyzed single-cell recordings within five subregions of the prefrontal cortex (PFC) of male macaques before and after training on a working-memory task. We found fine-grained but opposite gradients of intrinsic and seasonal timescales that mainly appeared after training. Intrinsic timescales decreased whereas seasonal timescales increased from posterior to anterior subregions within both dorsal and ventral PFC. Moreover, training was accompanied by increases in proportions of neurons that exhibited intrinsic and seasonal timescales. These effects were comparable to the emergence of response selectivity due to training. Finally, task selectivity accompanied opposite neural dynamics such that neurons with task-relevant selectivity exhibited longer intrinsic and shorter seasonal timescales. Notably, neurons with longer intrinsic and shorter seasonal timescales exhibited superior population-level coding, but these advantages extended to the delay period mainly after training. Together, our results provide evidence for plastic, fine-grained gradients of timescales within PFC that can influence both single-cell and population coding, pointing to the importance of these timescales in understanding cognition.

Significance statement

Recent studies have demonstrated that neural responses exhibit dynamics with different timescales that follow a certain order or hierarchy across cortical areas. While the hierarchy of timescales is consistent across different tasks, it is unknown if these timescales emerge only after training or if they represent inherent properties of neurons. To answer this question, we estimated multiple timescales in neural response across five subregions of the monkeys’ lateral prefrontal cortex before and after training on a working-memory task. Our results provide evidence for fine-grained gradients related to certain neural dynamics. Moreover, we show that these timescales depend on and can be modulated by training in a cognitive task, and contribute to encoding of task-relevant information at single-cell and population levels.
Association of mitochondrial fucosyltransferase TbFUT1 with the assembly of the mitochondrial FoF1-ATP synthase in bloodstream formTrypanosoma brucei
Authors: Duncan Samuel M. , Smithson Laura , Tinti Michele , Vaughan Susan , Ferguson Michael A.J.
Published: September 2023

The geneTbFUT1encodes an essential fucosyltransferase which, unexpectedly, localises to the mitochondrion of the protist parasiteTrypanosoma brucei. The expression ofTbFUT1is required for the maintenance of mitochondrial membrane potential (ΨΔm) in the bloodstream form (BSF) of the parasite, but the precise functions of TbFUT1 are unknown. Here, we demonstrate that depletion of TbFUT1 causes the accumulation of dyskinetoplastid cells; i.e., cells lacking concatenated complexes of mini- and maxicircle kinetoplast DNA (kDNA), the mitochondrial DNA of these organisms. Morphological analysis by serial face block-scanning electron microscopy showed that the dyskinetoplastid mitochondria were otherwise unperturbed with respect to structure and volume. Proteomics analyses showed that TbFUT1 depletion caused a decrease in the steady-state levels of several subunits of the Fo-subcomplex and peripheral stalk components of the mitochondrial FoF1-ATP synthase, as well as a pronounced reduction in mitochondrial ribosomal large subunit (LSU) proteins and more minor reduction in small subunit (SSU) proteins. TbFUT1 was rendered redundant with respect to cell survival and ΨΔm generation upon F1-γWT/L262Pmutation; a mutation that allows the generation of ΨΔm in the absence of mitochondrial translation. Additionally, depletion of TbFUT1 no longer perturbs kDNA replication in these cells, indicating that dyskinetoplasty is a downstream consequence of impaired ΨΔm. Depletion of TbFUT1 in wild type cells leads to the collapse of ΨΔm via a functional FoF1-ATP synthase complex. We therefore conclude these mutants are inhibited in the synthesis of Fo-subcomplex components and, thus, impairing the assembly of functional FoF1-ATP synthase complexes. Curiously, mitochondrial transcript levels exhibit similar changes in abundance after FUT1 ablation in the parental and F1-γWT/L262Pmutants. Further, the ∼5-fold overexpression of TbFUT1 in theTbFUT1conditional knockout mutant under permissive conditions selectively inhibits the formation of the fully RNA-edited A6 transcript by an unknown mechanism, partially suppressing FoF1-ATP synthase assembly in these mutants. Together, these data suggest that mitochondrial fucosylation is essential for the assembly of protein complexes containing kDNA encoded subunits.
SARS-CoV-2 hijacks fragile X mental retardation proteins for efficient infection
Authors: Garvanska Dimitriya H. , Alvarado Rojelio E. , Mundt Filip Oskar , Nilsson Emma , Duel Josephine Kerzel , Coscia Fabian , Lindqvist Richard , Lokugamage Kumari , Johnson Bryan A. , Plante Jessica A. , Morris Dorothea R. , Vu Michelle N. , Estes Leah K. , McLeland Alyssa M. , Walker Jordyn , Crocquet-Valdes Patricia A. , Mendez Blanca Lopez , Plante Kenneth S. , Walker David H. , Weisser Melanie Bianca , Overby Anna K. , Mann Matthias , Menachery Vineet D. , Nilsson Jakob
Published: September 2023

Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1 and FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replicationin vitroand have delayed disease onsetin vivo. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins for efficient infection and provides molecular insight to the possible underlying molecular defects in fragile X syndrome.
Resolving the climatic and ecological drivers of geographical gradients in avian sexual selection
Authors: Barber Robert A. , Yang Jingyi , Yang Chenyue , Barker Oonagh , Janicke Tim , Tobias Joseph A.
Published: September 2023

Sexual selection, one of the central pillars of evolutionary theory, has powerful effects on organismal morphology, behaviour and population dynamics. However, current knowledge about geographical variation in this evolutionary mechanism and its underlying drivers remains highly incomplete, in part because standardized data on the strength of sexual selection is sparse even for well-studied organisms. Here we use information on mating systems – including the incidence of polygamy and extra-pair paternity – to quantify the intensity of sexual selection in 10671 (>99.9%) bird species distributed worldwide. We show that avian sexual selection varies latitudinally, peaking at higher latitudes, although the gradient is reversed in the world’s most sexually selected birds – specialist frugivores – which are strongly associated with tropical forests. Phylogenetic models further reveal that the strength of sexual selection is explained by temperature seasonality coupled with a suite of climate-associated factors, including migration, diet, and territoriality. Overall, these analyses suggest that climatic conditions leading to short, intense breeding seasons, or highly abundant and patchy food resources, increase the potential for polygamy in birds, driving latitudinal gradients in sexual selection. Our findings help to resolve longstanding debates about spatial variation in evolutionary mechanisms linked to reproductive biology, and provide a comprehensive species-level dataset for further studies of selection and phenotypic evolution in the context of global climatic change.
Inhibition of the type IV secretion system from antibiotic-resistantHelicobacter pyloriclinical isolates supports the potential of Cagα as an anti-virulence target
Authors: Oudouhou Flore , Morin Claire , Bouin Mickael , Gaudreau Christiane , Baron Christian
Published: September 2023

Helicobacter pyloriresistance to antibiotics is a growing problem and it increasingly leads to treatment failure. While the bacterium is present worldwide, the severity of the clinical outcomes is highly dependent on the geographical origin and genetic characteristics of the strains. One of the major virulence factors identified inH. pyloriis thecagpathogenicity island (cagPAI), which encodes a type IV secretion used to translocate effectors into human cells. Here, we investigated the genetic variability of thecagPAI among 13 antibiotic-resistantH. pyloristrains that were isolated from patient biopsies in Québec. Seven of the clinical strains carried thecagPAI, but only four could be readily cultivated under laboratory conditions. We observed variability of the sequences of CagA and CagL proteins that are encoded by thecagPAI. All clinical isolates induce interleukin-8 secretion and morphological changes upon co-incubation with epithelial gastric cancer cells and two of them produce extracellular T4SS pili. Finally, we demonstrate that molecule 1G2, a small molecule inhibitor of the Cagα protein from the model strainH. pylori26695, reduces interleukin-8 secretion in one of the clinical isolates. Co-incubation with 1G2 also inhibits the assembly of T4SS pili, suggesting a mechanism for its action on T4SS function.
Lipid scrambling is a general feature of protein insertases
Authors: Li Dazhi , Rocha-Roa Cristian , Schilling Matthew A. , Reinisch Karin M. , Vanni Stefano
Published: September 2023

Glycerophospholipids are synthesized primarily in the cytosolic leaflet of the endoplasmic reticulum (ER) membrane and must be equilibrated between bilayer leaflets to allow the ER and membranes derived from it to grow. Lipid equilibration is facilitated by integral membrane proteins called “scramblases”. These proteins feature a hydrophilic groove allowing the polar heads of lipids to traverse the hydrophobic membrane interior, similar to a credit-card moving through a reader. Nevertheless, despite their fundamental role in membrane expansion and dynamics, the identity of most scramblases has remained elusive. Here, combining biochemical reconstitution and molecular dynamics simulations, we show that lipid scrambling is a general feature of protein insertases, integral membrane proteins which insert polypeptide chains into membranes of the ER and organelles disconnected from vesicle trafficking. Our data indicate that lipid scrambling occurs in the same hydrophilic channel through which protein insertion takes place, and that scrambling is abolished in the presence of nascent polypeptide chains. We propose that protein insertases could have a so-far overlooked role in membrane dynamics as scramblases.
The effect of entrepreneurial leadership traits on corporate sustainable development and firm performance: a resource-based view
Authors: Razzaque Anjum , Lee In , Mangalaraj George
Published: September 2023

Purpose

This study aims to empirically assess entrepreneurial leadership skills’ role in Corporate Sustainable Development (CSD) and firm performance (FP). This study considers five specific entrepreneurial traits: innovativeness, creativity, analytical thinking, emotional intelligence and passion and motivation. The motivation for this investigation stems from concerns over micro-firms vulnerabilities and small and medium enterprises (SMEs) lacking proper leadership skills. This study is guided by the resource-based view theory and conducted during the pandemic, offering insights into firms operating under constrained conditions.

Design/methodology/approach

Confirmatory factor analysis and structural equation modeling (SEM), were used on survey responses from 321 Bahraini firms. This study’s data collection occurred under environmental uncertainties due to the pandemic and provides a unique context for understanding CSD and entrepreneurial leadership skills under high business/environmental uncertainty.

Findings

The findings reveal that entrepreneurial leadership skills positively impact CSD and firm performance through creativity, passion and motivation. However, innovativeness negatively affects CSD and FP. Furthermore, CSD positively influences firm performance.

Research limitations/implications

Theoretical and practical implications, plus limitations, are also discussed in this study.

Practical implications

Understanding entrepreneurial leadership skills effect on CSD and firm performance in SMEs is important as SEMs are prone to fail in the early years. This study’s findings and its implications help guide SME leaders in furthering their entrepreneurial leadership skills to foster CSD and firm performance.

Originality/value

This study contributes to comprehending the crucial role of entrepreneurial skills, during uncertain times of the pandemic, for SMEs’ survival. It provides valuable insights for firms operating in competitive environments, offering a unique perspective on the required entrepreneurial skills and their effect on CSD and firm performance.
Appraising alternative building technologies adoption in low-cost housing provision to achieving Sustainable Development Goal 11
Authors: Ebekozien Andrew , Aigbavboa Clinton Ohis , Samsurijan Mohamad Shaharudin
Published: September 2023

Purpose

Though alternative building technologies (ABTs) have been encouraged to address accessible and affordable issues in low-cost housing (LCH) provision, their adoption is still overwhelmed with encumbrances. The encumbrances that hinder ABT adoption require an in-depth study, especially in developing countries like Nigeria. However, studies regarding ABT and its role in improving Nigeria's LCH to achieve Sustainable Development Goal (SDG) 11 are scarce. This research investigates encumbrances to ABT adoption in Nigeria's LCH provision and suggests feasible measures to prevent or reduce the encumbrances, thereby improving achieving SDG 11 (sustainable cities and communities).

Design/methodology/approach

This research utilised qualitative research and adopted a face-to-face interview as the primary data collection. The interviewees comprised ABT practitioners and end users in Nigeria who were chosen by a convenient sampling technique. The study's data were analysed manually through a thematic approach.

Findings

This study shows that stakeholders should embrace ABT in LCH provision to improve achieving SDG 11 in Nigeria. Also, it clustered the perceived 20 encumbrances to ABT adoption in LCH provision into government/policymaker, housing developers/building contractors, ABT users and ABT manufacturers-related issues in Nigeria's context. This study suggested mechanisms to mitigate encumbrances to ABT adoption in LCH provision, thereby improving achieving SDG 11.

Originality/value

This research adds to the limited literature by analysing ABT adoption encumbrances in Nigeria's LCH provision, which could assist policy formulation for the uptake of ABT in LCH provision and improve achieving Goal 11.
Forms of falsified online reviews: the good, the bad, and the downright ugly
Authors: Istanbulluoglu Doga , Harris Lloyd C.
Published: September 2023

Purpose

Falsified online reviews (FORs) are the published/viewable consumer-generated online content regarding a firm (or its representatives) or its services and goods that is, to some degree, untruthful or falsified. The purpose of this study is first to explore the nature of FORs, focusing on reviewers' interpretations and refections on falsity, intent, anonymity and the target of their FOR. Secondly, the authors examine the valence and veracity dimensions of FORs and introduce a typology to differentiate their variations.

Design/methodology/approach

using an exploratory research design, 48 interviews were conducted with participants who post online reviews on social media about their experiences with food and beverage serving outlets.

Findings

The results show four common forms of FORs on social media. These are reviews focused on equity equalizing, friendly flattery, opinionated opportunism and malicious profiteering.

Research limitations/implications

The authors provide exploratory and in-depth information via interviews, but do not analyse the content of FORs.

Practical implications

Firms should be aware of varieties of FORs and that these may not be limited to malicious content. This is important in terms of showing that in dealing with FORs, a one-size-fits-all approach will not work. FORs are not always entirely fabricated, and instead various levels of falseness are observed, ranging from slight alterations to complete fabrications.

Originality/value

Previous research explored how to identify and differentiate FORs from truthful ones, focusing on the reviews or how they are perceived by readers. However, comparatively little is known of the reviewers of FORs. Hence, this study focuses on reviewers and offers new insights into the nature of FORs by identifying and examining the main forms of FORs on social media.
Salutogenic environment: the effect of environmental quality of hospital public spaces (EQHPS) on patients’ sense of coherence
Authors: Ghaffari Faezeh , Shabak Maryam , Norouzi Nima , Nayyeri Fallah Siyamak
Published: September 2023

Purpose

This study aims at identifying the key perceived environmental attributes that can influence patients’ sense of coherence (SOC) in hospital public spaces and can improve hospital quality to create a salutogenic environment.

Design/methodology/approach

In total, 205 patients from the two hospitals in Sari City, Iran, participated in a questionnaire survey. The data were analyzed through structural equation modeling using partial least squares to investigate the impact of environmental qualities of public spaces on patients’ SOC.

Findings

Results confirmed that public spaces’ quality is positively associated with patients’ SOC. Accessibility has the most effective role in patients’ SOC, closely followed by relationability and intelligibility indicators. Environmental comfort also influences patients’ SOC in hospital public spaces. In comparison, the quality of the visibility is less important to patients’ SOC.

Practical implications

Findings will help hospital managers and designers to identify influential factors to improve the quality of health-care environments. Furthermore, the study will provide a picture of patients’ views and SOC intentions regarding public spaces in health-care environments.

Originality/value

To the authors’ knowledge, there is a lack of studies on the relationship between hospital public spaces and users’ SOC. Thus, this study investigates the experiences and perceptions of patients toward the quality of public spaces in hospital environments in physical, social and psychological aspects to find out its effects on patients’ SOC.
The role of information and communication technology in modernizing the courts: a case of Nepali judiciary
Authors: Paudel Krishna Prasad
Published: September 2023

Purpose

The purpose of this paper is to investigate the practices of information and communication technology (ICT) in modernizing the courts. In this context, this paper focuses on the usage of ICT in the Nepali judiciary system involving both judicial and court administration to automate judicial activities.

Design/methodology/approach

A narrative case study was conducted to identify the current status of technology in the judiciary system concerning court automation and administration. The information was gathered from justice, case registration officer, bench officer and admin personnel.

Findings

This study shows that technological intervention is made in the Nepali judiciary to automate judicial activities. The judicial activities, such as case registration, case automation, case hearing, the decision of cases and cause list, are of high priority and are managed through case management software. Furthermore, it demands an innovative learning environment within the judiciary to strengthen the capacity of the employees of the judiciary in the field of ICT.

Research limitations/implications

This study anticipates the participant’s perception and practical aspects of technology to modernize the courts to provide better and more effective service to its stakeholders. This study carried out the perceptions of the justice, bench officer, case registration officer and admin personnel. The voice of the other stakeholders was not carried out.

Practical implications

This paper establishes the practical aspects of ICT in modernizing the courts to provide better services to its stakeholders. It also replicates the status of ICT in the Nepali judiciary.

Originality/value

This paper tries to establish the practical implications of ICT along with its importance in the judiciary of Nepal.
The influence of information asymmetry on the interaction between voluntary corporate disclosure and cost of equity: evidence from publicly traded Indian enterprises
Authors: Bhatia Aparna , Kaur Amanjot
Published: September 2023

Purpose

The purpose of this paper is to investigate whether information asymmetry mediates the relationship between disclosure and cost of equity.

Design/methodology/approach

The study is based on a sample of 500 companies listed in Bombay Stock Exchange for a period of six years from 2015 to 2021. Panel data regression is applied to analyze the relationship between voluntary disclosure, cost of equity and information asymmetry. Mediation effect of information asymmetry is tested with the help of Barron and Kenny’s (1986) approach.

Findings

Findings suggest that in case of Indian companies, disclosure reduces cost of equity directly and indirectly through mediation of information asymmetry. Indian investors value credible information for better estimation of future returns, supporting the validity of estimation risk and stock market liquidity hypothesis, which proposes an inverse relationship between disclosure and cost of equity.

Research limitations/implications

Managers can use the findings to strategize their disclosure policy and secure funds at lower cost. Shareholders can monitor managerial actions by demanding credible disclosures. Government too can encourage voluntary disclosure by providing special incentives to the firms.

Originality/value

This study is a pioneering research that investigates the mediating influence of information asymmetry between disclosure and cost of equity with reference to the Indian corporate landscape.
The use of outcome measures and factors affecting use in adult social care occupational therapy services in the UK
Authors: Davenport Sharon , Underhill Ann
Published: September 2023

Purpose

This study aims to explore which outcome measures are used by occupational therapy staff in adult social care settings in the UK, and the factors affecting use of outcome measures.

Design/methodology/approach

A quantitative descriptive research design was used, using a cross-sectional study to explore occupational therapy staff views on the use of outcome measures. A 38-question survey was developed on Microsoft Forms. Recruitment occurred online over a three-week period in 2021 via the social media platform “Twitter”. Results were analysed using Excel using descriptive statistics and qualitative results used thematic analysis.

Findings

Participants (n = 20) used a range of outcome measures (13) in adult social care settings in the previous 12 months. Standardised measures were used by half the sample in the previous 12 months. The Therapy Outcome Measure and Barthel Index were in most use. The breadth of adult social care practice and practical factors such as caseload and lack of a meaningful tool were found to be barriers to outcome measure use. Facilitators included service improvement, accountability, use of audit and professional occupational therapy leadership.

Research limitations/implications

The overall use of outcome measures can be considered low in this setting, with manager support seen to be key to the use of outcome measures. Further research is needed to investigate nationwide use.

Practical implications

Training, time and manager support are key to use of standardised tests and outcome measures in the adult social care settings. The use of occupational performance measures should be considered to demonstrate unique professional impact.

Originality/value

This contemporary study reveals use of outcome measures within occupational therapy adult social care services in the UK, which is an under researched and under published area.