bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Read Sequencing Increases Diagnostic Yield for Pediatric Sensorineural Hearing Loss
Authors: Redfield Shelby E. , Shao Wanqing , Sun Tieqi , Pastolero Adrian , Rowell William J. , French Courtney E. , Nolan Cillian , Holt J. Matthew , Saunders Christopher T. , Fanslow Cairbre , Lampraki Eirini Maria , Lambert Christine , Kenna Margaret , Eberle Michael , Rockowitz Shira , Shearer Aiden Eliot
Published: October 2024

The diagnostic yield of genetic testing for pediatric sensorineural hearing loss (SNHL) has remained at around 40% for over a decade despite newly discovered causative genes and the expanded use of exome sequencing (ES). This stagnation may be due to (1) a focus on coding regions of the genome and (2) an inability to resolve variants in complex genomic regions due to reliance on short-read sequencing technologies. Short-read genome sequencing (srGS) and long-read genome sequencing (lrGS) both provide exonic single nucleotide variant (SNV) and small indel detection at the same sensitivity as ES, but also evaluate intronic regions. lrGS provides improved resolution for structural variants (SV) and repetitive genomic regions. We sought to investigate the potential utility of lrGS in the diagnostic evaluation of a small cohort of patients with SNHL of unknown etiology after ES and srGS. 19 pediatric patients with SNHL underwent lrGS via PacBio SMRT sequencing. Sequencing data were processed using the PacBio WGS variant pipeline. The diagnostic yield for this lrGS cohort was 4/19 (21%). Relevant variants detected only with lrGS included a hemizygous deletionin transwith a missense variant in an area of high genomic homology (OTOA) and two single nucleotide loss-of-function variantsin transto a known copy-number-loss for a gene with a highly homologous pseudogene (STRC). A complex inversion was identified in theMITFgene which was also identified on post-hoc analysis by srGS. LrGS provides improved resolution for complex genomic structural variation which may increase diagnostic yield for genetic pediatric SNHL, and, potentially, rare disease more broadly.
Multiscale Light Field Microscopy Platform for Multi-purpose Dynamic Volumetric Bioimaging
Authors: Bai Yangyang , Jones Matt , Ojeda Lauro Sebastian , Cuala Janielle , Cherchia Lynne , Georgia Senta K , Fraser Scott E , Truong Thai V
Published: October 2024

Light field microscopy (LFM) has emerged in recent years as a unique solution for fast, scan-free volumetric imaging of dynamic biological samples. This is achieved by using a microlens array in the detection path to record both the lateral and angular information of the light fields coming from the sample, capturing a 3-dimensional (3D) volume in a single 2-dimensional (2D) snapshot. In post-acquisition, the 3D sample volume is computationally reconstructed from the recorded 2D images, thus enabling unprecedented 3D capture speed, not limited by the typical constraint of physically scanning the focal plane over the sample volume. Up to date, most published LFM imaging setups have been specialized single-purpose platforms, optimized for a narrow performance window in field of view and resolution, thus hampering widespread adoption of LFM for biomedical research. Here, we present a versatile LFM platform for fast 3D imaging across multiple scales, enabling applications from cell to system-level biology on the same imaging setup. Our multiscale LFM is built as an add-on module to a conventional commercially available wide field microscope, and the various imaging applications, with different ranges of field of view and resolution, are achieved by simply switching between the standard microscope objectives available on the wide field microscope. Additionally, we provide an open-source end-to-end software package for calculating the system performance parameters, processing the experimentally measured point spread function, and light field 3D image reconstruction. We demonstrate the performance of our multiscale LFM platform through imaging the whole-brain activity map of seizures in larval zebrafish, calcium dynamics in ex vivo mouse pancreatic islets, and subcellular protein dynamics in cultured cells.
Chlorobaculum tepidumOuter Membrane Vesicles Are Likely a Significant Route for Biogenic Sulfur Transport
Authors: Noundou Vadesse L. , Levy Amalie , Modla Shannon , Yu Yanbao , Qu Jing , Hanson Thomas E.
Published: October 2024

Outer membrane-derived vesicles (OMVs) have been studied in different phyla of Gram-negative bacteria, most extensively in the Pseudomonadota, where they have been shown to participate in diverse biological and environmental processes. To date, the production of OMVs has not been reported in the Chlorobiaceae within the phylum Chlorobiota.Chlorobaculum. tepidumis the model organism for the Chlorobiaceae that synthesizes and consumes insoluble extracellular sulfur (S(0)) globules by an unknown mechanism. Here, we report evidence implicating outer membrane vesicles in biogenic S(0) globule synthesis. First we demonstrate thatCba. tepidumsecretes OMVs in the extracellular milieu, and that OMV yield and size vary with growth conditions, particularly sulfide concentration. A core of 28 proteins involved in diverse biological processes such as cell wall biogenesis, inorganic ion transport and metabolism were found to be shared between OMVs, extracellular S(0) globules andCba. tepidumintact cells. Multiple analytical methods indicated that OMVs contain S(0) and that OMVs and biogenic S(0) globules share protein and polysaccharide signatures, including lipooligosaccharides. Together these lines of evidence indicate thatCba. tepidum’s OMVs are one component of sulfur transport between cells and extracellular sulfur globules.

IMPORTANCE

All living cells must exchange material with their environment while maintaining cellular integrity. This is a particular challenge for materials that are not water soluble, yet many bacteria utilize insoluble materials for energy conservation and as nutrients for growth. Here we show thatCba. tepidummakes outer membrane vesicles and that these vesicles are likely involved in the exchange of material with extracellular elemental sulfur globules formed and consumed byCba. tepidumas part of its energy metabolism based on oxidizing reduced sulfur compounds like hydrogen sulfide. These data expand our basic understanding ofCba. tepidum’s metabolism. As elemental sulfur is an industrial by-product with a limited number of uses, the information here may help enable the use of additional sulfur compounds byCba. tepidumto drive the synthesis of biomass and/or specialty biochemicals from waste elemental sulfur by this autotrophic bacterium.
An all-in-one AAV vector for cardiac-specific gene silencing by an adenine base editor
Authors: Liu Zhanzhao , Yang Luzi , Yang Yuhan , Li Jiting , Chen Zhan , Guo Congting , Guo Qianhao , Li Qiuxuan , Sun Yueshen , Zhao Dongyu , Hu Xiaomin , Gao Fei , Guo Yuxuan
Published: October 2024

ABE editing outcomes are highly variable and unpredictable, depending on various factors. Therefore, the success rate of creating targeted A•T-to-G•C conversions using ABE is not high. But utilizing ABE to target RNA splicing sites for gene silencing has a higher success rate. Another challenge for base editing in the heart is that traditional ABE is too large in size, necessitating dual AAV delivery. Whether single AAV delivery can be achieved remains to be explored. In this study, we demonstrated how the diversity of Cas9 homologs and screening of sgRNAs can facilitate cardiac base editing. Single-AAV base editing outperformed dual-AAV systems in the heart, potentially benefiting from chromatin accessibility-guided sgRNA selection. These findings have important implications for the development of more effective and predictable base editing tools for cardiac gene therapy.
Unlocking the Potential of Low Quality Total RNA-seq Data: A Stepwise Mapping Approach for Improved Quantitative Analyses
Authors: Lee Jiwoon , Gim JungSoo
Published: October 2024

High-throughput sequencing assays face persistent challenges when analyzing low-quality RNAs, often assessed by the RNA integrity number (RIN). Current preprocessing methods and pipelines designed for mRNA-seq presume high-quality RNAs, overlooking the nuanced complexities arising from degraded transcripts in low-quality samples. This study questions the applicability of standard analysis pipelines, especially when sequencing low-quality total RNAs, which are sometimes the sole recourse for specific inquiries. To address this, we conducted a comprehensive investigation using large sequencing reads obtained from blood biospecimens with varying RINs. Introducing a novel mapping approach, termed ’stepwise mapping’, our systematic comparative analyses propose an optimal practice for total RNA-seq data analysis. Contrary to conventional mapping procedures, the ’stepwise mapping’ approach unveils additional transcriptome information, crucial for stable differential expression analysis, even with total RNA-seq data from specimens with relatively low RINs. Our method proves particularly valuable when analyzing limited specimens with low RNA quality.
Probabilistic modelling improves relative dating from gene phylogenies
Authors: Bernabeu Moisès , Armero Carmen , Gabaldón Toni
Published: October 2024

Establishing the timing of past evolutionary events is a fundamental task in the reconstruction of the history of life. State-of-the-art molecular dating methods generally involve the reconstruction of a species tree from conserved, vertically evolving genes, and the assumption of a molecular clock calibrated with the fossil record. Although this approach is extremely useful, its use is limited to speciation events and does not account for genes following different evolutionary paths. Recently, an alternative methodology for the relative dating of evolutionary events has been proposed that considers the distribution of branch lengths across sets of gene trees. Here, we validate this methodology using a fossil-calibrated phylogeny and propose a model-based formalisation using a Bayesian framework. Our analyses revealed that the normalisation of the compared branch lengths with branch lengths of a shared reference clade results in narrower distributions, allowing the correct inference of the relative ordering of evolutionary events. Moreover, we show that distributions of normalised lengths can be modelled using gamma or lognormal distributions. Finally, we demonstrate that inference of the posterior distribution of the mode allows accurate relative age estimation, as assessed by a strong correlation with the molecular clock-dated tree. Overall, we provide a novel, model-based approach to infer relative ages from sets of gene phylogenies.
Megakaryocytes assemble a three-dimensional cage of extracellular matrix that controls their maturation and anchoring to the vascular niche
Authors: Masson Claire , Scandola Cyril , Rinckel Jean-Yves , Proamer Fabienne , Janus-Bell Emily , Batool Fareeha , Osmani Naël , Goetz Jacky G. , Mallo Léa , Léon Catherine , Bornert Alicia , Poincloux Renaud , Destaing Olivier , Mansson Alma , Qian Hong , Lehmann Maxime , Eckly Anita
Published: October 2024

Megakaryocytes, the progenitor cells of blood platelets, play a crucial role in hemostasis by residing in the bone marrow and ensuring continuous platelet production. Unlike other hematopoietic cells, megakaryocytes do not enter the blood circulation intact. They remain anchored within the bone marrow while extending cytoplasmic protrusions called proplatelets through the sinusoidal endothelial barrier. These proplatelets subsequently fragment into functional platelets. This unique process of intravasation facilitates efficient platelet production while maintaining the megakaryocyte cell body within the bone marrow niche, thus preventing potential thrombotic complications. How the extracellular matrix (ECM) influences the delicate balance between megakaryocyte retention and proplatelet extension remains largely unknown. Here, we investigate the spatial organization and functional role of ECM components in the megakaryocyte vascular niche. Our findings reveal that laminin and collagen IV form three-dimensional (3D) ECM cages encompassing megakaryocytes and anchor them to the sinusoidal basement membrane. Gene deletion shows the existence of laminin α4 in the ECM cage that is necessary to maintain megakaryocyte-sinusoid interactions. Notably, megakaryocytes actively contribute to the ECM cage assembly; β1/β3 integrin knockout weakens these structures, increasing intravasation and entire megakaryocyte entry into circulation. The retention of megakaryocytes by these 3D ECM cages depends on dynamic remodeling processes. Inhibition of ECM proteolysis results in denser cage formation, increasing the frequence of immature megakaryocytes with impaired demarcation membrane system (DMS) development. Thus, the ECM cage represents a novel concept of an active and dynamic 3D microenvironment that is continuously remodeled and essential for maintaining megakaryocyte perivascular positioning. This specific microarchitecture guides megakaryocyte maturation and intravasation, underscoring the critical role of ECM microarchitecture and dynamics in megakaryocyte function.

Key Points

Megakaryocytes form a three-dimensional (3D) cage composed of laminin and collagen IV connected to the basement membrane surrounding them. This microarchitecture stabilizes megakaryocytes within their vascular niche.

β1/β3 integrins and MMP are key ECM cage regulators that assist megakaryocyte maturation and intravasation at the bone marrow-blood interface.
Irregular light schedules induce alterations on daily rhythms and gene expression in mice
Authors: Berbegal-Sáez Paula , Gallego-Landin Ines , Macía Javier , Valverde Olga
Published: October 2024

Synchronization of internal biological rhythms with external light-dark cycles is crucial for proper function and survival of the organisms, however modern life often imposes irregular light exposure, disrupting these internal clocks. This study investigated the effects of short-term shifted light-dark cycles on mice rhythmicity, and whether these alterations trigger molecular or behavioral changes. We evaluated locomotor activity, different behavioral domains and gene expression in the hypothalamus and medial prefrontal cortex. Despite non prominent behavioral impairments, such as anxiety or cognitive deficits, we observed a notable simplification in the locomotor activity patterns of the mice subjected to disrupted light-dark cycles. Molecular alterations included dysregulations in oscillations of core clock genes (Cry2,Per2) and disruptions in expression of genes involved in neuroplasticity, motivation, and stress responses, includingGluA1,Crhr2, andVipin both studied brain areas. Our study reveals that even brief light cycle shifts can disrupt circadian regulation at the molecular level, despite minimal behavioral changes. This molecular-behavioral discrepancy may suggest a complex adaptive response to drastic short-term light perturbations. Understanding the complex interplay between external light cues and internal biological rhythms regulation is crucial for mitigating the negative consequences of irregular light exposure on physiological processes and overall well-being.
Hypomorphic NOTCH1 Expression Alters Cardiomyocyte Cellular Architecture in Hypoplastic Left Heart Syndrome
Authors: Lewis Jordann , Lear Travis B. , Schlegel Brent , Woods Dominic , Rao Krithika , Sentis Amy , Tan Jay , Jagannathan Rajaganapathi , Javed Zaineb , Boudreau Aine N. , Nelson Timothy , Moulik Mousumi , Hempel Nadine , Chen Bill B. , Shiva Sruti , Rajasundaram Dhivyaa , Finkel Toren , Saraf Anita
Published: October 2024

NOTCH1 is a protein involved in cardiac development and mutations in NOTCH1 are implicated in left sided congenital heart disease, including hypoplastic left heart syndrome (HLHS). Therapeutic advances for HLHS patients have been hampered by the absence of suitable experimental models. Here, using human induced pluripotent stem cells (hiPSCs), we have generated a series of CRISPR-edited complex heterozygous hypomorphic mutations in NOTCH1 that recapitulate mutations seen in HLHS patients. These cells demonstrate the downregulation of genes associated with mitochondria, the actin cytoskeleton, and cardiomyocyte development. In addition, these hypomorphic NOTCH1 hiPSCs cells showed an increased propensity to differentiate towards non-cardiomyocyte lineages such as fibroblasts and smooth muscle cells, a finding confirmed in HLHS patient-derived myocardial tissue. Abnormalities in sarcomeric and mitochondrial architecture contributed to decreased ATP production, abnormal calcium transients, and reduced contractility. Using a split nano-luciferase system as a NOTCH1 intracellular reporter, we screened a library of FDA-approved compounds. Auranofin, an agent currently employed for rheumatoid arthritis, was identified as a candidate drug that could rescue impaired differentiation and contractility seen in the hypomorphic NOTCH1 model. These findings point to cell-autonomous abnormalities in hypomorphic NOTCH1 pre-cardiomyocyte cells that can be leveraged to identify potential therapeutic strategies for patients with severe congenital cardiac abnormalities.

Highlights:

CRISPR edited and patient-derived iPSCs with hypomorphic NOTCH1 expression were used to characterize a cell-based model of hypoplastic left heart syndrome.

Hypomorphic NOTCH1 iPSCs have abnormalities in pathways associated with mitochondrial function, actin cytoskeleton, and cardiomyocyte development.

Hypomorphic NOTCH1 iPSCs have less pluripotency and tend to skew differentiation away from cardiomyocytes and towards fibroblasts and smooth muscle cells.

NOTCH1 is required for cardiac cytoskeletal and mitochondrial architecture, and to preserve contractility and ATP production.

A high-throughput drug screen identified auranofin as an agent that may benefit patients with hypoplastic left heart syndrome.
Covalent Stabilization of Collagen Mimetic Triple Helices and Assemblies by Dopa Crosslinking
Authors: Cole Carson C. , Pogostin Brett H. , Vardanyan Vardan H. , Cahue Kiana A. , Bui Thi H. , Farsheed Adam C. , Swain Joseph W.R. , Makhoul Jonathan , Dubackic Marija , Holmqvist Peter , Olsson Ulf , Kolomeisky Anatoly B. , McHugh Kevin J. , Hartgerink Jeffrey D.
Published: October 2024

Creating thermally stable collagen mimetic peptides (CMPs) is a persistent challenge. Nature leverages covalent crosslinkings to stabilize collagen’s signature triple helical tertiary structure and higher-order assemblies. Herein, we demonstrate that crosslinkings between levodopa (Dopa) and lysine, amino acids present in native collagen, can covalently stabilize the triple helix in collagen mimetic peptides. Since alkaline conditions catalyze the oxidation of the catechol on Dopa to a benzoquinone, while being in proximity to the nucleophilic lysine, we hypothesized that this reaction could be a facile method to covalently capture the supramolecular structure of CMPs by simply increasing the pH of the aqueous solvent with the addition of sodium hydroxide. This covalent capture strategy successfully stabilizes CMP homotrimers and a de novo designed ABC-type heterotrimer demonstrating that the Lysine-Dopa covalent bond is best templated by a supramolecular, axial cation–πpairwise interaction. In nature, collagen can hierarchically assemble into fibers. This behavior can be mimicked with the self-assembly of CMPs, but the resulting nanofibers typically exhibit thermal stability below body temperature. In a final application, we demonstrate that Dopa–Lysine covalent capture also enhances the thermal stability of CMP nanofibers well above 37 °C. This biomimetic covalent capture strategy can stabilize a wide variety of CMP systems and potentially enable the biomedical application of these materials.
Long-read metagenomics empowers precise tracking of bacterial strains and their genomic changes after fecal microbiota transplantation
Authors: Fan Yu , Ni Mi , Aggarwala Varun , Mead Edward A , Ksiezarek Magdalena , Kamm Michael A , Borody Thomas , Paramsothy Sudarshan , Kaakoush Nadeem O , Grinspan Ari , Faith Jeremiah J , Fang Gang
Published: October 2024

Fecal microbiota transplantation (FMT) has revolutionized the treatment of recurrent Clostridioides difficile infection (rCDI) and is being evaluated across other diseases. Accurate tracking of bacterial strains, the functional units of the microbiota, that stably engraft in recipients is critical for understanding the determinants of strain engraftment, evaluating their correlation with clinical outcomes, and guiding the development of therapeutic bacterial consortia. While short-read sequencing has advanced our understanding of FMT, it faces challenges in the strain-level de novo metagenomic assembly of microbiome samples. In this study, we described a novel framework, LongTrack, that uses long-read metagenomic assemblies and reliable informatics tailored for FMT strain tracking. We first highlighted LongTrack advantage over short-read approaches especially when multiple strains co-exist in the same sample. We then showed LongTrack uncovered hundreds of engrafted strains across six FMT cases of rCDI and inflammatory bowel disease patients, validated by complementary bacterial culturing. Furthermore, beyond conventional strain tracking, long reads also allowed us to assess the genomic and epigenomic stability of successfully engrafted strains during the 5-year follow-ups, revealing structural variations in their genomes, which may be associated with strain adaptation in a new host environment. Combined, our study advocates the incorporation of long-read sequencing to enhance strain tracking in future FMT studies, paving the way for the development of more effective defined biotherapeutic as an alternative to FMT.
The Plasmodium falciparum NCR1 membrane protein is a novel antimalarial target that exports cholesterol to maintain membrane homeostasis
Authors: Zhang Zhemin , Lyu Meinan , Han Xu , Bandara Sepalika , Cui Meng , Istvan Eva S. , Geng Xinran , Tringides Marios L. , Gregor William D. , Miyagi Masaru , Oberstaller Jenna , Adams John H. , Zhang Youwei , Nieman Marvin T. , von Lintig Johannes , Goldberg Daniel E. , Yu Edward W.
Published: October 2024

Malaria is an extremely devastating parasitic infection that kills over half a million people each year. It is the leading cause of death in many developing countries, in part, due to a lack of resources and readily available therapeutics. Unfortunately, the most prevalent and deadliest causative agent of malaria,Plasmodium falciparum, has developed resistance to nearly all currently available antimalarial drugs. TheP. falciparumNiemann-Pick Type C1-related (PfNCR1) transporter has been identified as a druggable target, as it is required for membrane homeostasis of the parasite. However, the structure and detailed molecular mechanism of this membrane protein are not yet available. Here we present three structures of PfNCR1 both in the absence and presence of the functional inhibitor MMV009108 at resolutions between 2.98 Å and 3.81 Å using single-particle cryo-electron microscopy (cryo-EM). The data suggest that PfNCR1 binds cholesterol and forms a cholesterol transport tunnel to modulate the composition of the parasite plasma membrane. Cholesterol efflux assays substantiate this as they show that PfNCR1 is an exporter capable of extruding cholesterol from the membrane. Additionally, the inhibition mechanism of MMV009108 appears to be due to a direct blockage of PfNCR1, preventing this transporter from shuttling cholesterol.
STIX: Long-reads based Accurate Structural Variation Annotation at Population Scale
Authors: Zheng Xinchang , Chowdhury Murad , Mirpochoev Behzod , Clauset Aaron , Layer Ryan M , Sedlazeck Fritz J
Published: October 2024

The prioritization of Structural Variants (SV), which is needed to rank and identify potential pathogenic alleles, is still in its infancy. This is exemplified over gnomAD only being able to annotate 33.5% of GIAB SVs. To overcome this, we present the first long-read based annotation resource for both GRCh38 and CHM13-T2T reference using STIX. In contrast to previous methods, STIX indexes SV-informative long-reads themselves, can thus be easily extended and accurately annotate all SV types including insertions. STIX successfully annotated 95.9% of GIAB Tier1 SVs. STIX further improved cancer based SV prioritization by highlighting 3,563 SV from COSMIC being common in the population. We further showcase that mosaic SV can be independently gained and may be widely spread throughout the population. This highlights the need for accurate SV population frequency annotation to further facilitate the adoption of SV via long-read sequencing in medical research and clinical applications.
Targeting an Olfactory Receptor Mitigates High Residual Platelet Reactivity and Arterial Thrombosis Through Actin Cytoskeleton Depolymerization
Authors: Aggarwal Anu , Josyula Vara Prasad VN , Wang Nancy , Yang Moua , Shim Young Jun , Kennedy Quinn P. , Samuel Reina , Sangwan Naseer , Guntupalli Suman , Godwin Matthew , Ali Mariya , Jennings Courtney , Rajasekar Bhairavi , Scalise Alliefair , Park Huijun Edelyn , Stauffer Shaun , McCrea Keith , McIntyre Thomas , Cameron Scott J.
Published: October 2024

Background

Despite antiplatelet therapy, some patients remain at high risk for ischemic events due to medication non-responsiveness or High Residual Platelet Reactivity (HRPR). Our goal was to target an orphan G-Protein-Coupled Receptor (GPCR) on platelets belonging to the olfactory receptor family as a new antithrombotic strategy.

Methods

Using an engineered reporter cell line expressing Olfactory Receptor 2L13 (OR2L13) that was recently identified as an orphan GPCR to limit platelet reactivity, we performed a high-throughput screen (HST) of non-odorant bioactive compounds with counter-screen validation, followed by studies to determine changes in platelet function in healthy subjects and in patients with coronary artery disease and peripheral artery disease. Phospho-proteomics identified key signal transduction pathways, and a variety ofex vivoassays andin vivofunctional studies examined the impact of an identified non-odorant compound on platelet signaling, platelet biomechanics, and thrombosis.

Results

We identified 6 ligands specific for OR2L13 that function as receptor agonists, leading to the suppression of platelet aggregation and α-granule exocytosis via P2Y12,PAR1, Thromboxane Receptor (TxR) and glycoprotein VI (GPVI) receptors, suggesting involvement of common downstream mediator. The lead OR2L13 agonist identified phosphorylates heat shock protein 27 (HSP27) and depolymerizes the platelet filamentous actin cytoskeleton which was further confirmed in a clot retraction assay (CCF0054500 clot area 70.6 vs. vehicle clot area 5.2, P<0.0001). This anti-thrombotic effect of the OR2L13 agonist was reversed by a HSP27 inhibitor (clot area 3.6, P<0.0001). In a murine cremaster arterial injury model, platelet accumulation at the injury site was reduced by 88.9% by the lead OR2L13 agonist compared to vehicle (P<0.0003) without altering fibrin generationin vivo, or interfering with the coagulation cascade, and without impairing the protective mechanism of platelet hemostasis.

Conclusion

We describe and characterize the first non-olfactory tool to target an olfactory receptor for the purpose of inhibiting platelet activation and thrombosis through downstream HSP27 in a comprehensive investigation using a first-of-its kind platelet inhibitor targeting an orphan platelet GPCR.
IQD2 recruits KLCR1 to the membrane-microtubule nexus to promote cytoskeletal mechano-responsiveness in leaf epidermis pavement cells
Authors: Buhl Jonas , Klemm Sandra , Kölling Malte , Ruhnow Felix , Ihling Christian , Tüting Christian , Dahiya Pradeep , Patzsch Jacqueline , Colin Leia , Stamm Gina , Sinz Andrea , Kastritis Panagiotos L. , Persson Staffan , Bürstenbinder Katharina
Published: October 2024

Plant cells experience a variety of mechanical stresses from both internal and external sources, including turgor pressure, mechanical strains arising from heterogeneous growth between neighboring cells, and environmental factors like touch from soil, rain, or wind [1,2]. These stresses serve as signals at the cell-, tissue- and organismal level to coordinate plant growth during development and stress responses [3]. In plants, the physical cell wall-plasma membrane-microtubule continuum is proposed to be integral in transducing mechanical signals from the exterior to intracellular components [4–6]. Cortical microtubules (CMTs) rapidly reorient in response to mechanical stress to align with the maximal tensile stress direction [7,8]. Several studies proposed that CMTs themselves may act as stress sensors; the precise mechanisms involved in the regulation of CMTs and the modes of sensing, however, are still not clearly understood. Here, we show that IQD2 and KLCR1 are enriched at CMTs in proximity to the plasma membrane. IQD2, which is abona fidemicrotubule-associated protein, promotes microtubule localization of KLCR1. By combining cross-linking mass spectrometry (XL-MS) and computational modeling with structure-function studies, we present first experimental insights into the composition and structure of IQD2-KLCR1 complexes. Further, we demonstrate that the IQD2-KLCR1 module is a positive regulator of microtubule mechano-responses in pavement cells. Collectively, our work identifies the IQD2-KLCR1 module as novel regulator of mechanostress-mediated CMT reorientation and provides a framework for future mechanistic studies aimed at a functional dissection of mechanotransduction at the plasma membrane-CMT interface during growth and plant morphogenesis.

Highlights

IQD2 and KLCR1 localize to the plasma membrane-microtubule nexus

IQD2 is required for efficient microtubule targeting of KLCR1in planta

IQD2 physically interacts with KLCR1 and microtubules

The IQD2-KLCR1 module promotes mechano-stress induced microtubule reorganization
Dark matter induced baryonic feedback in galaxies
Authors: Acevedo Javier F. , An Haipeng , Boukhtouchen Yilda , Bramante Joseph , Richardson Mark L. A. , Sansom Lucy
Published: October 2024

We demonstrate that nongravitational interactions between dark matter and baryonic matter can affect structural properties of galaxies. Detailed galaxy simulations and analytic estimates demonstrate that dark matter which collects inside white dwarf stars and ignites type Ia supernovae can substantially alter star formation, stellar feedback, and the halo density profile through a dark matter induced baryonic feedback process, distinct from usual supernova feedback in galaxies.

Published by the American Physical Society
2024
Climate change literacy objectives for construction professionals in Zimbabwe
Authors: James Mellinda , Moyo Tirivavi , Moyo Cynthia
Published: September 2024

Purpose

Construction professionals' literacy incapacity exacerbates their vulnerability to climate change hazards on construction projects. Therefore, this study sought to determine climate change literacy objectives for Zimbabwean construction professionals. Climate change-literate construction professionals can significantly strengthen resilience and adaptive capability within the built environment.

Design/methodology/approach

The positivist approach employed a cross-sectional questionnaire survey strategy to collect quantitative data from construction professionals (Architects, Civil/Structural engineers, Project managers and Quantity surveyors) working in 280 registered consultancy and construction firms in Zimbabwe. The data were analysed using mean scores, normalisation, Kruskall–Wallis tests and factor analysis.

Findings

The respondents’ perceptions of the most critical climate change literacy objectives included knowledge of sustainable material utility, designing for resilient structures and understanding how climate change affects workers' physical and mental well-being. Generally, consensus on the nature of climate literacy objectives was evident. The factor analysis determined three components: stakeholder and climate information-related interventions, carbon and environmental footprint-related literacy and climate systems and indigenous knowledge-related literacy. Construction professionals can interpret climate change information through the determined objectives, contribute to reducing carbon and environmental footprint and improve project outcomes.

Research limitations/implications

A limitation was that a quantitative method was only employed; a concurrent qualitative inquiry could have mined more diverse views. Professional bodies and tertiary institutions can design climate change programmes based on the determined climate change literacy objectives for construction professionals.

Originality/value

The study determined climate change literacy objectives for construction professionals in Zimbabwe to enable them to respond to climate change hazards.
Leading from a distance: nurturing trust in virtual and crisis environments
Authors: Gamage Ancy , Muchiri Michael , Shahid Sehrish , Rashid Tanzil
Published: September 2024

Purpose

This study draws on the Social Process of Leadership (SPL) to identify the necessary behavioural leadership characteristics for trust-building in virtual crisis environments.

Design/methodology/approach

The study employs an in-depth qualitative case-study approach that is embedded in local contexts. Multiple sources of data – organisational documents, in-depth qualitative interviews, observational evidence and field notes – were used in the study. Interviews were informed by a purposeful sampling strategy and were semi-structured. This allowed the interviewer to use prompts to follow up with unanticipated issues raised by participants. Thematic analysis was conducted using NVivo.

Findings

Three key themes (related to how leaders nurture trust in virtual and crisis contexts) emerged from the data. These relate to nurturing trust by (1) optimising and providing a clear vision through reconfigured and personalised communication structures; (2) minimising uncertainty, optimising and modelling values-based behaviours and (3) enhancing adaptability and performance.

Research limitations/implications

The study extends the applicability of this theoretical approach to remote workplaces. It also contributes to the literature on crisis leadership by showcasing how leaders’ crisis responses based on SPL help organisations navigate disruptions. Limitations regarding the small sample size and the one case study context exist.

Practical implications

Organisations should invest in leadership and resilience and build strong remote/hybrid working models in preparation for future crises.

Originality/value

Despite the growing popularity of SPL, there is limited work on how leaders implement SPL processes to build and maintain trust in virtual workplaces. Furthermore, SPL has not yet been applied in highly disruptive work contexts, like those created by the pandemic.
The contribution of organic private label products to private label share outcomes
Authors: Hoskins Jake , Konuk Faruk Anıl , Machin Jane Emma
Published: September 2024

Purpose

The growing demand for sustainable consumption motivates retailers to consider including organic private label products in private label assortments to attract and serve health and environmentally conscious consumers, while also possibly improving the image of the private label brand as well. This study aims to examine the impact of prioritizing organic private label products in private label assortments on private label share outcomes.

Design/methodology/approach

Theoretical predictions are empirically examined using a comprehensive store panel sales data set covering 50 distinct metropolitan markets in the USA from 2008 to 2011 in the yogurt product category.

Findings

Findings indicate that private label products may provide strategic value for certain retailers, based on a variety of private label assortment, national brand competition and retailer characteristic dimensions.

Research limitations/implications

This research serves as initial empirical evidence on how organic products may influence private label category share. Future research should consider additional product categories and geographic markets and also seek to understand consumer perceptual factors in more detail.

Practical implications

Retail managers can better understand the role that organic products play in private label portfolios.

Originality/value

While much previous work has examined how organic products sell relative to conventional products and a sizable literature has investigated private label brand strategy, little research has explicitly examined the role of organic products within private label assortments.
The impact of attention and task performance on antiphishing performance: a multigoal perspective
Authors: Pan Shihe , Kuem Jungwon
Published: September 2024

Purpose

People are often recognized as the weakest part of thwarting phishing attacks. The goal of preventing phishing can conflict with the goal of keeping a good level of productivity in daily work; however, we still lack an understanding of this multigoal scenario. This paper aims to develop and test a new model of antiphishing performance, especially in relation to individuals' task performance in daily work. Drawing on the extended multiple-goal pursuit model (MGPM*), we examined the relationship between task performance at a time point and the subsequent antiphishing performance as well as how this relationship differs across varying types of phishing emails and attention levels to phishing cues.

Design/methodology/approach

We tested the model by conducting a field experiment with a survey questionnaire. Four legitimate work emails and four phishing emails (consisting of two work-related and two work-unrelated emails) were sent to 357 participants. The data were analyzed using generalized estimating equations.

Findings

The results indicate that task performance at a time point has a curvilinear relationship with subsequent antiphishing performance. This relationship is moderated by the types of phishing emails and individuals' attention to phishing cues. For work-related phishing emails, task performance is negatively associated with antiphishing performance when it reaches an intermediate level; however, when task performance is low, or high to an extent, it is positively related to antiphishing performance. For work-unrelated phishing emails, there is a positive association between task performance and antiphishing performance. Moreover, attention to phishing cues moderates the curvilinear relationship between task performance and antiphishing performance such that when task performance reaches an intermediate level, as attention to phishing cues increases, the relationship between task performance and antiphishing performance will turn from negative to positive.

Practical implications

This paper has practical implications that bear on the conflict between antiphishing performance and task performance.

Originality/value

This paper sheds light on the potential of the extended multiple-goal pursuit model in studying antiphishing behavior.
Artificial intelligence and its applications in the context of accounting and disclosure
Authors: Al-Okaily Manaf
Published: September 2024

Purpose

The purpose of this paper is to examine whether artificial intelligence (AI) increases data and information quality in the accounting and disclosure context.

Design/methodology/approach

Data were collected from financial managers, who are working in listed Jordanian firms in the Amman Stock Exchange. SmartPLS software based on the Partial Least Squares Structural Equation Modeling approach was used to test hypotheses.

Findings

The empirical results reached the acceptance of all hypotheses, and this means that all hypothesized relationships were positive, as the impact of AI was positive on data and information quality in the accounting and disclosure context, and also the adoption of digital disclosure mediated the relationship between AI and the quality of financial data and information, and hence, all hypotheses were statistically supported in the context of Jordan.

Originality/value

This study broadened the literature by proposing a research model that defines some of the main factors for determining financial managers’ perceptions of issues with digital financial disclosure adoption and its impact on financial data and information quality. By illuminating the relevance of these issues in the presence of the mandate of digital disclosure, this study sheds some light on digital disclosure regulators in making future policies for digital disclosure adoption among the different sectors such as financial, service and industrial in the Jordanian context.
Exploring aggressive tax planning dynamics: the impact of investment opportunity sets and free cash-flow surplus
Authors: Ghazalat Anas
Published: September 2024

Purpose

This study aims to investigate how investment opportunity sets (IOs) and free cash-flow (FCF) surpluses affect aggressive tax planning (ATP). This research focuses on examining the correlation between these factors and delves into how ATP, perceived as a tool for exploiting legal loopholes, plays a central role.

Design/methodology/approach

This study uses panel data analysis techniques on a sample of 1,248 firm-observations gathered from nonfinancial enterprises in Jordan that are listed in the Amman Stock Exchange (ASE) between the years 2008 and 2019. The Driscoll–Kraay regression model (fixed effect) is enlisted to avoid the inconsistency of the slope across individual units and time period.

Findings

The findings indicate that the IOs does not affect ATP. However, there is a significant negative effect of FCF surplus on ATP. Furthermore, consistent with positive accounting theory the data reveal that all of these control variables exert a substantial positive influence on ATP.

Research limitations/implications

This study concentrates on nonfinancial firms listed in the ASE, thereby constraining the applicability of the results to alternative contexts. Nevertheless, the findings of this study enhance comprehension regarding the extent of ATP and bear policy implications for policymakers regarding the structuring of future tax systems aimed at reducing the prevalence of tax avoidance behaviors. Thus, future research should conduct longitudinal studies to capture temporal dynamics.

Originality/value

This study contributes to the existing literature on ATP by focusing on using the Wilson tax-shelter model as a precise proxy. It fills gaps in prior research by exploring connections between IOs, FCF and ATP. The findings offer novel insights into the dynamics of tax planning strategies and contribute to the broader understanding of tax management practices.
Discerning the state of the art in Italy of voluntary disclosure on biodiversity and endemic species
Authors: Solimene Silvia , Coluccia Daniela , Fontana Stefano , Gulluscio Carmela , Bernardo Alessandro , Carnegie Garry D.
Published: September 2024

Purpose

This study aims to examine the extent and quality of biodiversity reporting within publicly traded companies in Italy during 2022, amidst growing calls worldwide for enhanced corporate environmental responsibility.

Design/methodology/approach

The study proposes a framework derived from existing biodiversity reporting literature and international guidelines on the topic. Using data from companies’ non-financial reports, the voluntary biodiversity disclosure index is quantified on disclosed information. Various quality reporting characteristics are also deepened. Sector-specific analysis is conducted across 11 industries.

Findings

Approximately 30% of companies in the sample release information on their biodiversity practices/initiatives regarding biodiversity and extinction loss risks. Quantitative analysis reveals a general commitment to disclosure yet falls short of optimal standards. Qualitative insights suggest a genuine intention towards reporting exists, with notable gaps in future orientation, double materiality and mitigation strategies. The quality analysis underscores that the reporting is mainly generalised, narrative and disaggregated concerning actions to restore habitats and ecosystems.

Research limitations/implications

A limitation of this study is the observation of annual reports during one reporting period. Future studies of longer duration would provide cross-period insights into corporate behaviour.

Practical implications

Policymakers should implement regulations and guidelines specifically tailored to biodiversity reporting, providing clear frameworks and standards for companies. Collaborative initiatives between governments, businesses and environmental organisations offer potential to develop best practices and facilitate knowledge-sharing in biodiversity reporting.

Social implications

Collaborative initiatives between governments, businesses and environmental organisations offer potential to develop best practices and facilitate knowledge sharing in biodiversity reporting.

Originality/value

The study contributes to future biodiversity disclosure research by introducing a comprehensive framework that fosters stakeholder trust and environmental accountability. It also sheds light on biodiversity stewardship among Italian companies, under EU directives.
Police leaders’ perspectives on their ability to support employee wellbeing in Australia: lack of time, training or support?
Authors: Sharafizad Fleur , Hernandez Grande Aglae , Farr-Wharton Benjamin
Published: September 2024

Purpose

Policing organizations in Australia are increasingly expected to eliminate or mitigate psychosocial risks in the workplace to promote employee wellbeing. New leadership skills are required, as police leaders play a key role in supporting the physical and mental health of their staff. This study aims to investigate police leaders’ perceptions about their ability to support employee wellbeing, and the ways in which they would like their organization to equip them for this important task.

Design/methodology/approach

Qualitative thematic analysis was conducted on the narratives provided by 156 Australian police leaders in response to a series of open-ended questionnaire questions.

Findings

Drawing on the conservation of resources theory, the themes identified indicate that police leaders are hindered in their ability to support the wellbeing of their staff by their own increasing workload in a context of reduced resourcing, the continuing stigma around mental health issues, a lack of knowledge and skills about how to support employee wellbeing and a lack of support from senior management.

Practical implications

Overall, the study highlights the way in which new work, health and safety guidelines place additional responsibilities on police leaders for which many report not feeling prepared. Findings suggest that bespoke leadership training may be required to assist police leaders in supporting the mitigation of psychosocial hazards in the workplace.

Originality/value

Considering continuously evolving psychosocial safety guidelines, this paper makes a unique contribution to contemporary knowledge by focusing on the role and readiness of police leaders in Australia to lessen the psychological impact of police work on officers in an increasingly complex policing context. Additionally, practical implications and recommendations are discussed and offered.