bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccinations in patients diagnosed with an autoimmune disorder receiving an immunosuppressive agent: a best practice implementation project
Authors: Loflin Betty , Upchurch Linda , Palokas Michelle , Christian Robin
Published: January 2024

Introduction:

Immunosuppressed patients face increased health risks due to infections such as influenza or COVID-19. Scientific evidence supports improved health-related outcomes in this patient population, such as reduced hospitalizations, with up-to-date vaccinations. The project setting, a community-based rheumatology clinic, did not have a vaccination record specific to the needs of immunosuppressed patients, which may have led to suboptimal immunization status in these patients.

Objective:

This project aimed to promote evidence-based practices regarding the use of vaccinations in patients diagnosed with autoimmune disorders receiving immunosuppressive agents.

Methods:

This project used the JBI evidence implementation framework to promote best practices regarding vaccination. Two audit criteria were identified using a JBI evidence summary. Baseline audits identified gaps between the evidence and current practice. Barriers to best practice were then identified, and strategies implemented. Post-implementation audits measured changes in compliance.

Results:

Baseline audits revealed 67% compliance with the two best practices. Barriers included a lack of provider awareness of the current vaccination recommendations for immunosuppressed patients and a lack of customizable vaccine records. Strategies to address these barriers included educating providers about current national vaccination recommendations and implementing a new patient vaccination history intake form. Post-implementation audits revealed 83% compliance, a 16% increase from baseline.

Conclusions:

This evidence-based implementation project enhanced best practices by educating providers and implementing an updated patient vaccination history form. Recommendations included improved compliance with the use of the new form and assessing the effectiveness and usability of a customizable electronic form that interfaced with the clinic's electronic medical records.
Genomic epidemiology of the clinically dominant clonal complex 1 in the Listeria monocytogenes population in the UK
Authors: Fotopoulou Emily T. , Jenkins Claire , Barker Clare R. , Painset Anais , Didelot Xavier , Simbo Ameze , Douglas Amy , Godbole Gauri , Jorgensen Frieda , Gharbia Saheer , McLauchlin† Jim
Published: January 2024

Listeria monocytogenes

is a food-borne pathogen, typically affecting the elderly, immunocompromised patients and pregnant women. The aim of this study was to determine the population structure of

L. monocytogenes

clonal complex 1 (CC1) in the UK and describe the genomic epidemiology of this clinically significant CC. We interrogated a working dataset of 4073 sequences of

L. monocytogenes

isolated between January 2015 and December 2020 from human clinical specimens, food and/or food-production environments. A minimum spanning tree was reconstructed to determine the population structure of

L. monocytogenes

in the UK. Subsequent analysis focused on

L. monocytogenes

CC1, as the cause of the highest proportion of invasive listeriosis in humans. Sequencing data was integrated with metadata on food and environmental isolates, and information from patient questionnaires, including age, sex and clinical outcomes. All isolates either belonged to lineage I (n=1299/4073, 32%) or lineage II (n=2774/4073, 68%), with clinical isolates from human cases more likely to belong to lineage I (n=546/928, 59%) and food isolates more likely to belong to lineage II (n=2352/3067, 77%). Of the four largest CCs, CC1 (n=237) had the highest proportion of isolates from human cases of disease (CC1 n=160/237, 67.5 %; CC121 n=13/843, 2 %; CC9 n=53/360, 15 %; CC2 n=69/339, 20%). Within CC1, most cases were female (n=95/160, 59%, P=0.01771) and the highest proportion of cases were in people >60 years old (39/95, 41%, P=1.314×10−6) with a high number of them aged 20–39 years old (n=35/95, 37%) most linked to pregnancy-related listeriosis (n=29/35, 83%). Most of the male cases were in men aged over 60 years old (40/65, 62%), and most of the fatal cases in both males and females were identified in this age group (42/55, 76%). Phylogenetic analysis revealed 23 5 SNP single linkage clusters comprising 80/237 (34 %) isolates with cluster sizes ranging from 2 to 19. Five 5 SNP clusters comprised isolates from human cases and an implicated food item. Expanding the analysis to 25 SNP single linkage clusters resolved an additional two clusters linking human cases to a potential food vehicle. Analysis of demographic and clinical outcome data identified CC1 as a clinically significant cause of invasive listeriosis in the elderly population and in women of child-bearing age. Phylogenetic analysis revealed the population structure of CC1 in the UK comprised small, sparsely populated genomic clusters. Only clusters containing isolates from an implicated food vehicle, or food processing or farming environments, were resolved, emphasizing the need for clinical, food and animal-health agencies to share sequencing data in real time, and the importance of a One Health approach to public-health surveillance of listeriosis.
Transcriptomic Analysis Identifies Candidate Genes for Differential Expression duringXenopus laevisInner Ear Development
Authors: Virk Selene M. , Trujillo-Provencio Casilda , Serrano Elba E.
Published: January 2024

Background

The genes involved in inner ear development and maintenance of the adult organ have yet to be fully characterized. Previous genetic analysis has emphasized the early development that gives rise to the otic vesicle. This study aimed to bridge the knowledge gap and identify candidate genes that are expressed as the auditory and vestibular sensory organs continue to grow and develop until the systems reach postmetamorphic maturity.

Methods

Affymetrixmicroarrays were used to assess inner ear transcriptome profiles from threeXenopus laevisdevelopmental ages where all eight endorgans comprise mechanosensory hair cells: larval stages 50 and 56, and the post-metamorphic juvenile. Pairwise comparisons were made between the three developmental stages and the resulting differentially expressedX.laevisProbe Set IDs (Xl-PSIDs) were assigned to four groups based on differential expression patterns. DAVID analysis was undertaken to impart functional annotation to the differentially regulated Xl-PSIDs.

Results

Analysis identified 1510 candidate genes for differential gene expression in one or more pairwise comparison. Annotated genes not previously associated with inner ear development emerged from this analysis, as well as annotated genes with established inner ear function, such asoncomodulin,neurod1,andsp7. Notably, 36% of differentially expressed Xl-PSIDs were unannotated.

Conclusions

Results draw attention to the complex gene regulatory patterns that characterizeXenopusinner ear development, and underscore the need for improved annotation of theX. laevisgenome. Outcomes can be utilized to select candidate inner ear genes for functional analysis, and to promoteXenopusas a model organism for biomedical studies of hearing and balance.
Transforming chemigenetic bimolecular fluorescence complementation systems into chemical dimerizers using chemistry
Authors: Kumar Pratik , Gutu Alina , Waring Amelia , Brown Timothy A. , Lavis Luke D. , Tebo Alison G.
Published: January 2024

Chemigenetic tags are versatile labels for fluorescence microscopy that combine some of the advantages of genetically encoded tags with small molecule fluorophores. The Fluorescence Activating and absorbance Shifting Tags (FASTs) bind a series of highly fluorogenic and cell-permeable chromophores. Furthermore, FASTs can be used in complementation-based systems for detecting or inducing protein-protein interactions, depending on the exact FAST protein variant chosen. In this study, we systematically explore substitution patterns on FAST fluorogens and generate a series of fluorogens that bind to FAST variants, thereby activating their fluorescence. This effort led to the discovery of a novel fluorogen with superior properties, as well as a fluorogen that transforms splitFAST systems into a fluorogenic dimerizer, eliminating the need for additional protein engineering.
DNA-PKcs Suppresses Illegitimate Chromosome Rearrangements
Authors: Wang Jinglong , Sadeghi Cheyenne A , Frock Richard L
Published: January 2024

Two DNA repair pathways, non-homologous end joining (NHEJ) and alternative end joining (A-EJ), are involved in V(D)J recombination and chromosome translocation. Previous studies reported distinct repair mechanisms for chromosome translocation, with NHEJ involved in human and A-EJ in mice predominantly. NHEJ depends on DNA-PKcs, a critical partner in synapsis formation and downstream component activation. While DNA-PKcs inhibition promotes chromosome translocations harboring microhomologies in mice, its synonymous effect in humans is not known. We find partial DNA-PKcs inhibition in human cells leads to increased translocations and the continued involvement of a dampened NHEJ. In contrast, complete DNA-PKcs inhibition substantially increased microhomology-mediated end joining (MMEJ), thus bridging the two different translocation mechanisms between human and mice. Similar to a previous study on Ku70 deletion, DNA-PKcs deletion in G1/G0-phase mouse progenitor B cell lines, significantly impairs V(D)J recombination and generated higher rates of translocations as a consequence of dysregulated coding and signal end joining. Genetic DNA-PKcs inhibition suppresses NHEJ involvement entirely, with repair phenotypically resembling Ku70-deficient A-EJ. In contrast, we find DNA-PKcs necessary in generating the near-excusive MMEJ associated with Lig4 deficiency. Our study underscores DNA-PKcs in suppressing illegitimate chromosome rearrangement while also contributing to MMEJ in both species.
Structure of a lasso peptide bound ETB receptor provides insights into the mechanism of GPCR inverse agonism
Authors: Shihoya Wataru , Akasaka Hiroaki , Jordan Peter A. , Lechner Anna , Okada Bethany K. , Cruz Gabriella Costa Machado da , Sano Fumiya K. , Tanaka Tatsuki , Kawahara Ryo , Chaudhari Rajan , Masamune Hiroko , Burk Mark J. , Nureki Osamu
Published: January 2024

Lasso peptides exhibit a unique lariat-like knotted structure imparting exceptional stability and thus show promise as therapeutic agents that target cell-surface receptors. One such receptor is the human endothelin ETBreceptor, which is implicated in challenging cancers with poor immunotherapy responsiveness. TheStreptomyces-derived lasso peptide, RES-701-3, is a selective inhibitor for ETBand a compelling candidate for therapeutic development. However, meager production from a genetically recalcitrant host has limited further structure-activity relationship studies of this potent inhibitor. Here, we report cryo-electron microscopy structures of ETBreceptor in both its apo form and complex with RES-701-3, facilitated by a calcineurin-fusion strategy. Hydrophobic interactions between RES-701-3 and the transmembrane region of the receptor, especially involving two tryptophan residues, play a crucial role in RES-701-3 binding. Furthermore, RES-701-3 prevents conformational changes associated with G-protein coupling, explaining its inverse agonist activity. A comparative analysis with other lasso peptides and their target proteins highlights the potential of lasso peptides as precise drug candidates for G-protein-coupled receptors. This structural insight into RES-701-3 binding to ETBreceptor offers valuable information for the development of novel therapeutics targeting this receptor and provides a broader understanding of lasso peptide interactions with human cell-surface receptors.
Discovery of Waddington’s developmental canals elucidates the embryogenesis stability inCaenorhabditis elegans
Authors: Wang Jianguo , Xiao Long , Yao Zeqi , Deng Shanjun , Yang Jianrong , Wu Chung-I , Du Zhuo , He Xionglei
Published: January 2024

During embryogenesis, the cells in an embryo need to make numerous spatiotemporal decisions. However, there is inherent noise in each decision due to genetic or environmental fluctuations. How to suppress the noise accumulation to achieve stable embryonic end-products, a process known as Waddington’s developmental canalization, has been a major puzzle in biology since the 1940s. Previous studies have focused on the molecular noise within a cell instead of the cell noise within an embryo, thus providing indirect understandings (e,g., the well-known genetic capacitor Hsp90). In this study, we applied time-lapse microscopic imaging to capturing the spatiotemporal features of single cells, including cell position and cell cycle length, during the embryogenesis of approximately 2,100Caenorhabditis elegansembryos exposed to various genetic or environmental perturbations. By treating the deviation of a cell’s spatiotemporal feature from the expected value as noise, we modeled the transmission of noise from each mother cell to their daughters. We discovered pervasive mother-daughter negative feedbacks, which collectively constitute continuous and comprehensive ‘canals’ for suppressing noise accumulation along the developmental cell lineages, with the steepness (measuring noise suppression efficacy) and depth (measuring noise tolerance level) of the canals quantitatively defined. The learned quantitative rules enabled us to develop a cell-noise-based model that accurately predicts the nematode hatching phenotype, revealing how embryonic stochasticity could cause phenotypic disparity. With a high-dimensional mathematical tool we then proved the system stability of embryogenesis against the cell spatiotemporal noise. We also revealed several dozen canal-maintaining genes and proposed a novel association study framework that links embryonic cells rather than genetic variants with organismal traits. In sum, this study discovered and quantitatively characterized the developmental canals that directly stabilize embryogenesis in a metazoan, illuminating an 80-year-old puzzle and paving a way for studying the phenotypic plasticity and robustness of multicellular organisms from the perspective of embryogenesis.
Precision Genome Editing Unveils a Breakthrough in Reversing Antibiotic Resistance: CRISPR/Cas9 Targeting of Multi-Drug Resistance Genes in Methicillin-ResistantStaphylococcus aureus
Authors: Ates Aysegul , Tastan Cihan , Ermertcan Safak
Published: January 2024

Antibiotic resistance poses a global health crisis, limiting the efficacy of available therapeutic agents and hindering the development of new antibiotics. The pharmaceutical industry’s waning interest in antibiotic production further exacerbates this challenge. Addressing antibiotic resistance demands innovative solutions. Here, we explore the application of CRISPR-Cas-based antimicrobials as a pioneering approach to combat multidrug resistance. Our study focuses on the methicillin-resistant clinical Staphylococcus aureus (MRSA), a significant clinical threat. Utilizing CRISPR/Cas9 technology, we aimed to concurrently target methicillin (mecA), gentamicin (aacA), and ciprofloxacin (grlA, grlB) resistance genes, thereby altering the resistance profile and enhancing sensitivity to antibiotics. We engineered CRISPR plasmids containing sgRNAs specific to the target regions, which were subsequently electroporated into MRSA strains. Real-time Polymerase Chain Reaction (RT-PCR) assessed changes in resistance gene expression, while disk diffusion and broth microdilution methods determined alterations in resistance status. Western blotting analyzed changes in PBP2a expression, and Sanger sequence analysis confirmed mutations in target regions. Results revealed a statistically significant 1.5-fold decrease in mecA gene expression, 5.5-fold decrease in grlA gene, 6-fold decrease in grlB gene, and 4-fold decrease in aacA gene compared to the wild type strain, as determined by RT-PCR. Antibiotic susceptibility tests demonstrated the suppression of mecA, grlA, grlB, and aacA genes, resulting in the reversal of resistance to beta-lactam, quinolone, and aminoglycoside antibiotics. Western blot analysis showed 70% decrease in PBP2a expression, indicating the breakdown of beta-lactam resistance. Sanger sequence analysis confirmed point mutations in grlB and aacA genes, along with three-base mutations in grlA and mecA genes. Our findings underscore the potential of CRISPR/Cas9 technology to mitigate antibiotic resistance, offering a transformative strategy to restore the efficacy of existing antibiotics in the face of multidrug-resistant pathogens.
Flagella are required to coordinately activate competition and host colonization factors in response to a mechanical signal
Authors: Speare Lauren , Zhao Liang , Pavelsky Morgan N. , Jackson Aundre , Smith Stephanie , Tyagi Bhavyaa , Sharpe Garrett C. , Woo Madison , Satkowiak Lizzie , Bolton Trinity , Gifford Scott M. , Septer Alecia N.
Published: January 2024

Bacteria employ antagonistic strategies to eliminate competitors of an ecological niche. Contact-dependent mechanisms, such as the type VI secretion system (T6SS), are prevalent in host-associated bacteria, yet we know relatively little about how T6SS+ strains make contact with competitors in highly viscous environments, such as host mucus. To better understand how cells respond to and contact one another in such environments, we performed a genome-wide transposon mutant screen of the T6SS-wielding beneficial bacterial symbiont,Vibrio fischeri, and identified two sets of genes that are conditionally required for killing. LPS/capsule and flagellar-associated genes do not affect T6SS directly and are therefore not required for interbacterial killing when cell contact is forced yet are necessary for killing in high-viscosity liquid (hydrogel) where cell-cell contact must be biologically mediated. Quantitative transcriptomics revealed thatV. fischerisignificantly increases expression of both T6SS genes and cell surface modification factors upon transition from low-to high-viscosity media. Consistent with coincubation and fluorescence microscopy data, flagella are not required for T6SS expression in hydrogel. However, flagella play a key role in responding to the physical environment by promoting expression of the surface modification genes identified in our screen, as well as additional functional pathways important for host colonization including uptake of host-relevant iron and carbon sources, and nitric oxide detoxification enzymes. Our findings suggest that flagella may act as a mechanosensor forV. fischerito coordinately activate competitive strategies and host colonization factors, underscoring the significance of the physical environment in directing complex bacterial behaviors.

Significance

The physical environment can have dramatic effects on bacterial behavior, but little is known about how mechanical signals impact antagonistic interactions. Symbiotic bacteria use molecular weapons to eliminate competitors for limited space within highly viscous host tissue and mucus.

To better understand how the physical environment affects competition and adhesion within eukaryotic hosts, we used quantitative transcriptomics to reveal the flagella-dependent transcriptional response to bacterial transition from lower to a higher viscosity environment. This work revealed the T6SS interbacterial weapon is coordinately activated with host colonization factors, emphasizing the importance of integrating activation of interbacterial weapons into host colonization pathways to enhance a symbiont’s ability to successfully colonize the host while efficiently eliminating potential competitors from the host niche.
Image processing tools for petabyte-scale light sheet microscopy data
Authors: Ruan Xiongtao , Mueller Matthew , Liu Gaoxiang , Görlitz Frederik , Fu Tian-Ming , Milkie Daniel E. , Lillvis Joshua L. , Kuhn Alexander , Chong Johnny Gan , Hong Jason Li , Herr Chu Yi Aaron , Hercule Wilmene , Nienhaus Marc , Killilea Alison N. , Betzig Eric , Upadhyayula Srigokul
Published: January 2024

Light sheet microscopy is a powerful technique for high-speed 3D imaging of subcellular dynamics and large biological specimens. However, it often generates datasets ranging from hundreds of gigabytes to petabytes in size for a single experiment. Conventional computational tools process such images far slower than the time to acquire them and often fail outright due to memory limitations. To address these challenges, we present PetaKit5D, a scalable software solution for efficient petabyte-scale light sheet image processing. This software incorporates a suite of commonly used processing tools that are memory and performance-optimized. Notable advancements include rapid image readers and writers, fast and memory-efficient geometric transformations, high-performance Richardson-Lucy deconvolution, and scalable Zarr-based stitching. These features outperform state-of-the-art methods by over one order of magnitude, enabling the processing of petabyte-scale image data at the full teravoxel rates of modern imaging cameras. The software opens new avenues for biological discoveries through large-scale imaging experiments.
Hunting for peptide binders of specific targets with data-centric generative language models
Authors: Nie Zhiwei , Li Daixi , Chen Jie , Xu Fan , Liu Yutian , Fu Jie , Liu Xudong , Wang Zhennan , Ma Yiming , Wang Kai , Zhang Jingyi , Hu Zhiheng , Song Guoli , Ye Yuxin , Yin Feng , Zhou Bin , Liu Zhihong , Li Zigang , Gao Wen , Tian Yonghong
Published: January 2024

The increasing frequency of emerging viral infections calls for more efficient and low-cost drug design methods. Peptide binders have emerged as a strong contender to curb the pandemic due to their efficacy, safety, and specificity. Here, we propose a customizable low-cost pipeline incorporating model auditing strategy and data-centric methodology for controllable peptide generation.

A generative protein language model, pretrained on approximately 140 million protein sequences, is directionally fine-tuned to generate peptides with desired properties and binding specificity. The subsequent multi-level structure screening reduces the synthetic distribution space of peptide candidates regularly to identify authentic high-quality samples, i.e. potential peptide binders, atin silicostage. Paired with molecular dynamics simulations, the number of candidates that need to be verified in wet-lab experiments is quickly reduced from more than 2.2 million to 16. These potential binders are characterized by enhanced yeast display to determine expression levels and binding affinity to the target. The results show that only a dozen candidates need to be characterized to obtain the peptide binder with ideal binding strength and binding specificity. Overall, this work achieves efficient and low-cost peptide design based on a generative language model, increasing the speed ofde novoprotein design to an unprecedented level. The proposed pipeline is customizable, that is, suitable for rapid design of multiple protein families with only minor modifications.
Multiparameter-based photosynthetic state transitions of single phytoplankton cells
Authors: Harris Paul David , Eliezer Nadav Ben , Keren Nir , Lerner Eitan
Published: January 2024

Phytoplankton are a major source of primary production. Their photosynthetic fluorescence uniquely reports on their type, physiological state and response to environmental conditions. Changes in phytoplankton photophysiology are commonly monitored by bulk fluorescence spectroscopy, where gradual changes are reported in response to different perturbations such as light intensity changes. What is the meaning of such trends in bulk parameters if their values report ensemble averages of multiple unsynchronized cells? To answer this, we developed an experimental scheme that enables acquiring multiple fluorescence parameters, from multiple excitation sources and spectral bands. This enables tracking fluorescence intensities, brightnesses and their ratios, as well as mean photon nanotimes equivalent to mean fluorescence lifetimes, one cell at a time. We monitored three different phytoplankton species during diurnal cycles and in response to an abrupt increase in light intensity. Our results show that we can define specific subpopulations of fluorescence parameters for each of the phytoplankton species and in response to varying light conditions. Importantly, we identify the cells undergo well-defined transitions between these subpopulations that characterize the different light behaviors. The approach shown in this work will be useful in the exact characterization of phytoplankton cell states and parameter signatures in response to different changes these cells experience in marine environments, which will be useful in monitoring marine-related effects of global warming.

Significance Statement

Using three representatives of red-linage phytoplankton we demonstrate distinct photophysiological behaviors at the single cell level. The results indicate cell wide coordination into discrete cell states. We test cell state transitions as a function of light acclimation during diurnal cycle and in response to large intensity increases, which stimulate distinct photoprotective response mechanisms. The analysis was made possible through the development of flow-based confocal detection at multiple excitation and emission wavelengths monitoring both pigment composition and photosynthetic performance. Our findings show that with enough simultaneously recorded parameters per each cell, the detection of multiple phytoplankton species at their distinct cell states is possible. This approach will be useful in examining the response of complex natural marine populations to environmental perturbations.
Straightforward semi-quantitative MALDI-TOF MS based screening approach for selection of recombinant protein producing E. Coli
Authors: Kravtsov Ivan N. , Solovyev Andrey I. , Potemkina Eugenia A. , Kartashova Anastasya V. , Dmitrieva Maria A. , Danilova Kseniya V. , Tutykhina Irina L. , Polyakov Nikita B. , Egorova Daria A.
Published: January 2024

MALDI-TOF MS represents a rapid and cost-effective method for identifying proteins and microorganisms. When obtaining recombinant protein producers, differences in expression levels among transformants necessitate the conduction of a small-scale screening of expression levels. This study proposes a fast and easy method for screening clones producing recombinant proteins using MALDI-TOF MS. Various recombinant proteins were utilized to test the proposed method
Genomic Transfer via Membrane Vesicle: A Strategy of Giant Phage phiKZ for Early Infection
Authors: Antonova Daria , Nichiporenko Anna , Sobinina Mariia , Vishnyakov Innokentii E. , Moiseenko Andrey , Kurdyumova Inna , Khodorkovskii Mikhail , Sokolova Olga S. , Yakunina Maria V.
Published: January 2024

During infection, the giant phiKZ phage forms a specialized structure at the center of the host cell called the phage nucleus. This structure is crucial for safeguarding viral DNA against bacterial nucleases and for segregating the transcriptional activities of late genes. Here, we describe a morphological entity, the early phage infection vesicle (EPI vesicle), which appears to be responsible for earlier gene segregation at the beginning of the infection process. Using cryo-electron microscopy, electron tomography, and fluorescence microscopy with membrane-specific dyes, we found that the EPI vesicle is enclosed in a lipid bilayer originating, apparently, from the inner membrane of the bacterial cell. Our investigations further disclose that the phiKZ EPI vesicle contains both viral DNA and viral RNA polymerase (vRNAP). We have observed that the EPI vesicle migrates from the cell pole to the center, displaying co-localization with ChmA, the primary protein of the phage nucleus. While phage DNA is transported into the phage nucleus after phage maturation, the EPI vesicle remains outside. We hypothesized that the EPI vesicle acts as a membrane transport agent, efficiently delivering phage DNA to the phage nucleus while protecting it from the nucleases of the bacterium.
Saturated fatty acid-Coenzyme A supplementation restores neuronal energy levels, synaptic function, and protein homeostasis in hereditary spastic paraplegia
Authors: Saber Saber H. , Yak Nyakuoy , Yong Xuan Ling Hilary , Lu Siyuan , Binder Tobias , Purushothaman Reshinthine , Gaudin Arnaud , Harmer Jeffrey , Talbo Gert Hoy , van Waardenberg Ashley J , Anggono Victor , Balistreri Giuseppe , Joensuu Merja
Published: January 2024

Hereditary Spastic Paraplegia (HSP) type 54 is a complex childhood autosomal recessive neurodegenerative disorder characterized by impairments in both neuromuscular and cognitive functions. This condition arises from mutations in theDDHD2gene, which encodes for the phospholipase A1 enzyme DDHD2. Previous research has indicated that loss ofDDHD2results in lipid droplet accumulation in the brain, progressive apoptosis of motor neurons in the spinal cord, a reduction in cardiolipin content, and an increase in reactive oxygen species. However, the precise underlying mechanisms of HSP54 remains unclear. Our recent study demonstrated a robust increase in saturated free fatty acids (sFFAs), particularly myristic acid, during neuronal stimulation and memory acquisitionin vivoin the brains of mice andin vitroin primary neurons. This activity-dependent increase of sFFAs was blocked inDDHD2knockout mice (DDHD2-/-), suggesting that disturbed production of sFFAs underlies the neuronal pathology of HSP54. Here, using electron microscopy (EM) and live-cell confocal imaging, mass spectrometry and proteomics, electric field stimulation, as well as fluorometric and mitochondrial function assays in cultured primary neurons, we discovered that loss of DDHD2 leads to reduced levels of acetyl-coenzyme A (CoA) and ATP. Additionally, DDHD2 deficiency results in impaired respiratory function, altered mitochondrial morphology and distribution, a significant defect in synaptic vesicle recycling with an accumulation of large bulk endosomes in the presynapses, as well as an imbalance in global protein homeostasis. Our study further reveals that the combined administration of myristic acid and CoA (Myr-CoA) fully rescues mitochondrial function and ATP production within 48 hours. This intervention also leads to a marked restoration of neuronal protein homeostasis, providing the first demonstration of a potential combinatory therapeutic intervention for HSP54. Our findings demonstrate that the sFFAs released by the activity of DDHD2 play a central role in maintaining neuronal energy levels, synaptic function, and protein balance. The requirement for DDHD2 lipase activity in these processes can, therefore, be bypassed by supplementation of a preconjugated Myr-CoA.
Probing baryogenesis with radiative beauty decay and electron electric dipole moment
Authors: Hou Wei-Shu , Kumar Girish , Modak Tanmoy
Published: January 2024

With the Large Hadron Collider (LHC) running, we should probe electroweak baryogenesis (EWBG) while probing CP violation (CPV) with electron electric dipole moment (eEDM). Rooted in the flavor structure of the Standard Model (SM), the general two Higgs doublet model (g2HDM) with a second set of Yukawa couplings can deliver EWBG while surviving eEDM. We point out a chiral-enhanced top-bottom interference effect that makes b→sγ decay an exquisite window on EWBG and eEDM, and illustrate the importance of the ΔACP observable at Belle II.

Published by the American Physical Society
2024
Probing the Short-Distance Structure of the Quark-Gluon Plasma with Energy Correlators
Authors: Yang Zhong , He Yayun , Moult Ian , Wang Xin-Nian
Published: January 2024

Energy-energy correlators (EECs) are promising observables to study the dynamics of jet evolution in the quark-gluon plasma (QGP) through its imprint on angular scales in the energy flux of final-state particles. We carry out the first complete calculation of EECs using realistic simulations of high-energy heavy-ion collisions and dissect the different dynamics underlying the final distribution through analyses of jet propagation in a uniform medium. The EECs of γ-jets in heavy-ion collisions are found to be enhanced by the medium response from elastic scatterings instead of induced gluon radiation at large angles. In the meantime, EECs are suppressed at small angles due to energy loss and transverse momentum broadening of jet shower partons. These modifications are further shown to be sensitive to the angular scale of the in-medium interaction, as characterized by the Debye screening mass. Experimental verification and measurement of such modifications will shed light on this scale and the short-distance structure of the QGP in heavy-ion collisions.

Published by the American Physical Society
2024
The High-Pressure Freezing Laboratory for Macromolecular Crystallography (HPMX), an ancillary tool for the macromolecular crystallography beamlines at the ESRF
Authors: Carpentier Philippe , van der Linden Peter , Mueller-Dieckmann Christoph
Published: January 2024

This article describes the High-Pressure Freezing Laboratory for Macromolecular Crystallography (HPMX) at the ESRF, and highlights new and complementary research opportunities that can be explored using this facility. The laboratory is dedicated to investigating interactions between macromolecules and gases in crystallo, and finds applications in many fields of research, including fundamental biology, biochemistry, and environmental and medical science. At present, the HPMX laboratory offers the use of different high-pressure cells adapted for helium, argon, krypton, xenon, nitrogen, oxygen, carbon dioxide and methane. Important scientific applications of high pressure to macromolecules at the HPMX include noble-gas derivatization of crystals to detect and map the internal architecture of proteins (pockets, tunnels and channels) that allows the storage and diffusion of ligands or substrates/products, the investigation of the catalytic mechanisms of gas-employing enzymes (using oxygen, carbon dioxide or methane as substrates) to possibly decipher intermediates, and studies of the conformational fluctuations or structure modifications that are necessary for proteins to function. Additionally, cryo-cooling protein crystals under high pressure (helium or argon at 2000 bar) enables the addition of cryo-protectant to be avoided and noble gases can be employed to produce derivatives for structure resolution. The high-pressure systems are designed to process crystals along a well defined pathway in the phase diagram (pressure–temperature) of the gas to cryo-cool the samples according to the three-step `soak-and-freeze method'. Firstly, crystals are soaked in a pressurized pure gas atmosphere (at 294 K) to introduce the gas and facilitate its interactions within the macromolecules. Samples are then flash-cooled (at 100 K) while still under pressure to cryo-trap macromolecule–gas complexation states or pressure-induced protein modifications. Finally, the samples are recovered after depressurization at cryo-temperatures. The final section of this publication presents a selection of different typical high-pressure experiments carried out at the HPMX, showing that this technique has already answered a wide range of scientific questions. It is shown that the use of different gases and pressure conditions can be used to probe various effects, such as mapping the functional internal architectures of enzymes (tunnels in the haloalkane dehalogenase DhaA) and allosteric sites on membrane-protein surfaces, the interaction of non-inert gases with proteins (oxygen in the hydrogenase ReMBH) and pressure-induced structural changes of proteins (tetramer dissociation in urate oxidase). The technique is versatile and the provision of pressure cells and their application at the HPMX is gradually being extended to address new scientific questions.
The distribution of Cyclone Idai’s water impacts in Beira, Mozambique
Authors: McCordic Cameron , Raimundo Ines , Judyn Matthew , Willis Duncan
Published: January 2024

Purpose

Climate hazards in the form of cyclones are projected to become more intense under the pressures of future climate change. These changes represent a growing hazard to low lying coastal cities like Beira, Mozambique. In 2019, Beira experienced the devastating impact of Cyclone Idai. One of the many impacts resulting from this Cyclone was disrupted drinking water access. This investigation explores the distribution of Cyclone Idai’s impact on drinking water access via an environmental justice lens, exploring how preexisting water access characteristics may have predisposed households to the impacts of Cyclone Idai in Beria.

Design/methodology/approach

Relying on household survey data collected in Beira, the investigation applied a decision tree algorithm to investigate how drinking water disruption was distributed across the household survey sample using these preexisting vulnerabilities.

Findings

The investigation found that households that mainly relied upon piped water sources and experienced inconsistent access to water in the year prior to Cyclone Idai were more likely to experience disrupted drinking water access immediately after Cyclone Idai. The results indicate that residents in formal areas of Beira, largely reliant upon piped water supply, experienced higher rates of disrupted drinking water access following Cyclone Idai.

Originality/value

These findings question a commonly held assumption that informal areas are more vulnerable to climate hazards, like cyclones, than formal areas of a city. The findings support the inclusion of informal settlements in the design of climate change adaptation strategies.
Potential effects of customer-brand identification and self-representation on Aliexpress advocacy: a comparative study
Authors: Hussain Safdar , Shoukat Muhammad Haroon , Elgammal Islam , Khan Mukaram Ali , Selem Kareem M.
Published: January 2024

Purpose

Drawing on social identity theory (SIT), the current research highlights the sequential mediation effects of customer interaction, functional value and hedonic value in linking customer-brand identification and self-representation with online brand advocacy (OBA).

Design/methodology/approach

Data were gathered from 483 Egyptian and 595 non-Egyptian Aliexpress shopping platform customers, then analyzed using SmartPLS 4.

Findings

The multigroup analysis findings revealed that customer interaction and functional/hedonic values sequentially mediated the linkages of customer-brand identification and self-presentation with OBA for Egyptian and non-Egyptian user groups.

Originality/value

The novelty of this study is that it tested and validated customer interaction with the Aliexpress service scale, allowing for reflection on the interactive nature of this platform between Egyptian and non-Egyptian customers. SIT also lends credence to the idea that self-presentation mediates the effect of customer-brand identification on Aliexpress’s OBA, potentially shedding new light on this understudied dimension using a theoretical framework.
Elastic manufacturing: provisioning and deprovisioning production capacity to vary product volume and mix
Authors: Rama Murthy Sudhir , Sousa-Zomer Thayla Tavares , Minshall Tim , Velu Chander , Kazantsev Nikolai , McFarlane Duncan
Published: January 2024

Purpose

Advancements in responsive manufacturing have been supporting companies over the last few decades. However, manufacturers now operate in a context of continuous uncertainty. This research paper explores a mechanism where companies can “elastically” provision and deprovision their production capacity, to enable them in coping with repeated disruptions. Such a mechanism is facilitated by the imitability and substitutability of production resources.

Design/methodology/approach

An inductive study was conducted using Gioia methodology for this theory generation research. Respondents from 20 UK manufacturing companies across multiple industrial sectors reflected on their experience during COVID-19. Resource-based view and resource dependence theory were employed to analyse the manufacturers' use of internal and external production resources.

Findings

The study identifies elastic responses at four operational levels: production-line, factory, company and supply chain. Elastic responses that imposed variable-costs were particularly well-suited for coping with unforeseen disruptions. Further, the imitability and substitutability of manufacturers helped others produce alternate goods during the crisis.

Originality/value

While uniqueness of production capability helps manufacturers sustain competitive advantage against competitors during stable operations, imitability and substitutability are beneficial during a crisis. Successful manufacturing companies need to combine these two approaches to respond effectively to repeated disruptions in a context of ongoing uncertainties. The theoretical contribution is in characterising responsive manufacturing in terms of resource heterogeneity and resource homogeneity, with elastic resourcing as the underlying mechanism.
Investors in the Bangladeshi stock market: issues, behavioural biases and circumvention strategies
Authors: Chowdhury Nazreen Tabassum , Mahdzan Nurul Shahnaz , Rahman Mahfuzur
Published: January 2024

Purpose

This study aims to explore the underlying issues of behavioural biases in relation to stock market participation and the challenges of individual investors in Bangladesh. The study identifies behavioural biases affecting individuals’ stock market participation, their circumvention strategies and the importance of financial knowledge in encouraging the participation of individuals in the stock market.

Design/methodology/approach

Semi-structured interviews were used in this study to gather information from industry researchers, individual investors, brokers and institutional advisors. Twenty-two experts were contacted, and 13 agreed to participate in the interviews. The study then uses the thematic analysis method to report its findings.

Findings

This research shows that investors’ behavioural biases (such as loss aversion, herding, trust, gambler’s fallacy and risk tolerance) are among Bangladesh’s primary drivers of stock market participation. Circumvention strategies (such as poor corporate governance and agency costs) also play a part in individuals’ participation. These influences are in addition to the obvious factors of investment risks, poor infrastructure, poor regulation enforcement and the need for more sufficient investment products.

Research limitations/implications

This study conducted 13 interviews with expert subjects, which is a small sample size. However, the findings achieved saturation and cannot be ignored. Future research should use quantitative or experimental methods with a large sample size to validate the current findings.

Originality/value

This study is pioneering in the Bangladesh stock market, exploring the behavioural biases of investors’ participation in the market. This paper provides valuable insights into investor participation by discovering the underlying behavioural biases that have been continually ignored; these insights may also be relevant in frontier markets in Asian countries.
Investigating alternative avenues for financial behaviour change: moving beyond the traditional approach
Authors: Lučić Andrea , Uzelac Marija
Published: January 2024

Purpose

This study aims to explore possible behavioural change venues, beyond the traditional approach to financial education, using the capability-opportunity-motivation behaviour theoretical framework of behavioural change.

Design/methodology/approach

The study included 45, semi-structured, in-depth interviews of young adults to explore which elements of financial behaviour formation should interventions target to be effective.

Findings

To strengthen capability, the study recommends behavioural education and training for boosting financial knowledge and skills, enablement of financial independence and modelling for empowering self-control and reducing impulsiveness. To boost motivation, gamification of modelling is advised for boosting responsible financial behaviour as part of the identity and inducing consideration of future consequences. Persuasion is advised for inducing positive emotions while incentivization and coercion are advised for empowering self-conscious intentions. To rise opportunity, the study proposes incentivization and coercion imposed by parents, and governmental efforts regarding restriction, enablement and environmental restructuring.

Practical implications

The study brings recommendations for developing efficient interventions for strengthening responsible financial behaviour that may help design type-specific education programmes to promote responsible financial behaviour.

Originality/value

The present study attempts to explore new venues in intervention design that break away from the traditional approach of financial education focused on knowledge and skills that is proven to be ineffective
The impact of the forestland‐tenure disputes on the new type of forestry operating entity's long‐term investment: The intermediary effects on credit constraints
Authors: Xiao Hui , Hou Fangmiao , Li Xiaoyi , Wei Zhuoran , Wu Chengliang
Published: January 2024

In the context of the state's proposal to accelerate the development of new type of forestry operating entities in rural area, we provide an analysis of how forestland‐tenure disputes affect the long‐term investment behavior through credit constraints based on the perspective of forestland‐tenure disputes. Based on the survey data of 485 new type of forestry operating entities in nine provinces across China, the empirical analysis is conducted using the Tobit model and mediating effect model, while paying attention to the heterogeneity of management scale and different entity types on the impact of new type of forestry operating entity's long‐term investment behavior. The conclusions are as follows: both forestland‐tenure disputes and dispute areas have a significant negative impact on the new type of forestry operating entity's long‐term investment. In addition, forestland‐tenure disputes not only have a direct negative impact on the long‐term investment but also have an indirect negative impact on the long‐term investment by constraining the new type of forestry operating entity's bank loan and expanding the loan gap. It is suggested to improve the forestland trading market, regulate the order of trading, and implement the policy of forest tenure mortgage to provide stable policy guarantee and external conditions for fully activating the vitality of forestland management.
Health literacy in older adults receiving hemodialysis in Turkey: A cross‐sectional study
Authors: Uğurlu Ziyafet , Kav Sultan , Eler Çiğdem Özdemir , Kaya Semiha , Korkmaz Yasemin
Published: January 2024

Introduction

This study aimed to determine the health literacy level and related factors of older adults receiving hemodialysis treatment.

Methods

A cross‐sectional study was conducted at the five dialysis centers, using the information form and Turkish Health Literacy Survey‐32 (THLS‐32). A total of 336 older adults receiving hemodialysis treatment participated.

Results

The general health literacy score was found to be 25.69 ± 14.47. Based on the health literacy assessment scores, 62.5% of the participants were in the category of inadequate and limited level of health literacy. The lower level of education, perceived health status, income, and getting help in reading and writing were statistically significant predictors of the health literacy score.

Conclusion

The health literacy of older adults receiving hemodialysis treatment was inadequate and limited. Findings of this study emphasize the importance of integrating health literacy assessment in clinical care settings and supporting the health literacy of older adults receiving hemodialysis treatment.