bluuebunny/crossref_metadata_2025 huggingface dataset:
3D-Printing of Electroconductive MXene-based Micro-meshes in a Biomimetic Hyaluronic Acid-based Scaffold Directs and Enhances Electrical Stimulation for Neural Repair Applications
Authors: Woods Ian , Spurling Dahnan , Sunil Sandra , Maughan Jack , Gutierrez-Gonzalez Javier , McGuire Tara K. , Leahy Liam , Dervan Adrian , Nicolosi Valeria , O’Brien Fergal J
Published: April 2024

No effective treatments are currently available for central nervous system neurotrauma although recent advances in electrical stimulation suggest some promise in neural tissue repair. We hypothesized that structured integration of an electroconductive biomaterial into a tissue engineering scaffold could enhance electroactive signalling for neural regeneration.

Electroconductive 2D Ti3C2TxMXene nanosheets were synthesized from MAX-phase powder, demonstrating excellent biocompatibility with neurons, astrocytes and microglia. To achieve spatially-controlled distribution of these MXenes, melt-electrowriting was used to 3D-print highly-organized PCL micro-meshes with varying fibre spacings (low-, medium-and high-density), which were functionalized with MXenes to provide highly-tunable electroconductive properties (0.081±0.053-18.87±2.94 S/m). Embedding these electroconductive micro-meshes within a neurotrophic, immunomodulatory hyaluronic acid-based extracellular matrix (ECM) produced a soft, growth-supportive MXene-ECM composite scaffold. Electrical stimulation of neurons seeded on these scaffolds promoted neurite outgrowth, influenced by fibre spacing in the micro-mesh. In a multicellular model of cell behaviour, neurospheres stimulated for 7 days on high-density MXene-ECM scaffolds exhibited significantly increased axonal extension and neuronal differentiation, compared to low-density scaffolds and MXene-free controls. The results demonstrate that spatial-organization of electroconductive materials in a neurotrophic scaffold can enhance repair-critical responses to electrical stimulation and that these biomimetic MXene-ECM scaffolds offer a promising new approach to neurotrauma repair.
Morphological Study of Left–right Head Asymmetry inDoubledaya bucculenta(Coleoptera: Erotylidae: Languriinae)
Authors: Oda Hiroki , Nakamura Taro , Toki Wataru , Niimi Teruyuki
Published: April 2024

Left–right asymmetry in paired organs is well-documented across various species, including the claws of fiddler crabs and snail-eating snakes’ dentition. However, the mechanisms underlying these asymmetries remain largely elusive. This study investigatesDoubledaya bucculenta(Coleoptera: Erotylidae), a lizard beetle species known for pronounced left-sided asymmetry in adult female mandible and gena. Given that insect mouthparts comprise multiple functionally significant appendages, we aimed to clarify the degree of asymmetry extending beyond the mandibles and genae. Phenotypic morphology was assessed through trait measurement and asymmetry index calculations. Our detailed morphometric analyses revealed left-longer asymmetry not only in mandibles and genae but also in maxillae and labium. Notably, the degree of asymmetry in other mouthparts was generally less pronounced compared to outer mandibles, suggesting a potential influence of left mandible development on other mouthparts. Additionally, male mandibles exhibited region-specific asymmetry, potentially indicative of constrained evolutionary adaptations. This study enhances a comprehensive understanding of adult phenotype morphology and offers insights into the developmental basis of asymmetrical mouthparts.
The impact of micro-habitat fragmentation on microbial populations growth dynamics
Authors: Mant Dina , Orevi Tomer , Kashtan Nadav
Published: April 2024

Microbial communities inhabit almost every habitat on Earth and are essential to the function of diverse ecosystems. Most microbial habitats are not spatially continuous and well-mixed, but rather composed, at the microscale, of many isolated or semi-isolated local patches, resulting in partitioning of microbial populations into discrete local populations. The impact of this spatial fragmentation on population dynamics is not well-understood. Here, we study how fragmentations affect the growth dynamics of clonal microbial populations and how dynamics in individual patches dictate those of the whole metapopulation. To investigate this, we developed the µ-SPLASH, a novel ecology-on-a-chip platform, enabling the culture of microbes in microscopic landscapes comprised of thousands of microdroplets, spanning a wide range of sizes. Using the µ-SPLASH, we cultured the model bacteriaE. coliand based on time-lapse microscopy, analyzed the population dynamics within thousands of individual droplets at single-cell resolution. Our results reveal that growth curves vary dramatically with droplet size. While growth rates generally increase with drop size, reproductive success and the time to approach carrying capacity, display non-monotonic patterns. Combining µ-SPLASH experiments with computational modeling, we show that these patterns result from both stochastic and deterministic processes, and demonstrate the roles of initial population density, patchiness, and patch size distribution in dictating the local and metapopulation dynamics. This study reveals basic principles that elucidate the effects of habitat fragmentation and population partitioning on microbial population dynamics. These insights are imperative for a deeper understanding of natural microbial communities and have significant implications for microbiome engineering.
RNA language models predict mutations that improve RNA function
Authors: Shulgina Yekaterina , Trinidad Marena I. , Langeberg Conner J. , Nisonoff Hunter , Chithrananda Seyone , Skopintsev Petr , Nissley Amos J. , Patel Jaymin , Boger Ron S. , Shi Honglue , Yoon Peter H. , Doherty Erin E. , Pande Tara , Iyer Aditya M. , Doudna Jennifer A. , Cate Jamie H. D.
Published: April 2024

Structured RNA lies at the heart of many central biological processes, from gene expression to catalysis. While advances in deep learning enable the prediction of accurate protein structural models, RNA structure prediction is not possible at present due to a lack of abundant high-quality reference data1. Furthermore, available sequence data are generally not associated with organismal phenotypes that could inform RNA function2–4. We created GARNET (Gtdb Acquired RNa with Environmental Temperatures), a new database for RNA structural and functional analysis anchored to the Genome Taxonomy Database (GTDB)5. GARNET links RNA sequences derived from GTDB genomes to experimental and predicted optimal growth temperatures of GTDB reference organisms. This enables construction of deep and diverse RNA sequence alignments to be used for machine learning. Using GARNET, we define the minimal requirements for a sequence- and structure-aware RNA generative model. We also develop a GPT-like language model for RNA in which overlapping triplet tokenization provides optimal encoding. Leveraging hyperthermophilic RNAs in GARNET and these RNA generative models, we identified mutations in ribosomal RNA that confer increased thermostability to theEscherichia coliribosome. The GTDB- derived data and deep learning models presented here provide a foundation for understanding the connections between RNA sequence, structure, and function.
The RNA binding protein Nab2 regulates splicing of the RhoGEFtriotranscript to govern axon and dendrite morphology
Authors: Lancaster Carly L. , Yalamanchili Pranav S. , Goldy Jordan N. , Leung Sara W. , Corbett Anita H. , Moberg Kenneth H.
Published: April 2024

TheDrosophilaRNA binding protein (RBP) Nab2 acts in neurons to regulate neurodevelopment and is orthologous to the human intellectual disability-linked RBP, ZC3H14. Nab2 governs axon projection in mushroom body neurons and limits dendritic arborization of class IV sensory neurons in part by regulating splicing events in ~150 mRNAs. Analysis of theSex-lethal(Sxl) mRNA revealed that Nab2 promotes an exon-skipping event and regulates m6A methylation onSxlpre-mRNA by the Mettl3 methyltransferase. Mettl3 heterozygosity broadly rescuesNab2nullphenotypes implying that Nab2 acts through similar mechanisms on other RNAs, including unidentified targets involved in neurodevelopment. Here, we show that Nab2 and Mettl3 regulate the removal of a 5’UTR intron in thetriopre-mRNA. Trio utilizes two GEF domains to balance Rac and RhoGTPase activity. Intriguingly, an isoform of Trio containing only the RhoGEF domain, GEF2, is depleted inNab2nullnervous tissue. Expression of Trio-GEF2 rescues projection defects inNab2nullaxons and dendrites, while the GEF1 Rac1-regulatory domain exacerbates these defects, suggesting Nab2-mediated regulation Trio-GEF activities. Collectively, these data identify Nab2-regulated splicing as a key step in balancing Trio GEF1 and GEF2 activity and show that Nab2, Mettl3, and Trio function in a common pathway that shapes axon and dendrite morphology.

Significance Statement

DrosophilaNab2, ortholog of the human RBP ZC3H14 mutated in inherited intellectual disability, acts through unknown RNA targets to control axon and dendrite morphology.

This study shows that Nab2 and the Mettl3 methyltransferase guide splicing oftriomRNA, which encodes a conserved GEF-domain protein. Intron retention intriomRNA leads to an imbalance in levels of two Trio GEF domains in Nab2-deficient neurons and restoring this balance rescues neuronal defects.

The authors conclude that Nab2 control oftriosplicing is required to pattern axon and dendrite growth and suggests that ZC3H14 may play a similar role in the vertebrate brain.
Rapid profiling of transcription factor-cofactor interaction networks reveals principles of epigenetic regulation
Authors: Inge MM , Miller R , Hook H , Bray D , Keenan JL , Zhao R , Gilmore TD , Siggers T
Published: April 2024

Transcription factor (TF)-cofactor (COF) interactions define dynamic, cell-specific networks that govern gene expression; however, these networks are understudied due to a lack of methods for high-throughput profiling of DNA-bound TF-COF complexes. Here we describe theCofactorRecruitment (CoRec) method for rapid profiling of cell-specific TF-COF complexes. We define a lysine acetyltransferase (KAT)-TF network in resting and stimulated T cells. We find promiscuous recruitment of KATs for many TFs and that 35% of KAT-TF interactions are condition specific. KAT-TF interactions identify NF-κB as a primary regulator of acutely induced H3K27ac. Finally, we find that heterotypic clustering of CBP/P300-recruiting TFs is a strong predictor of total promoter H3K27ac. Our data supports clustering of TF sites that broadly recruit KATs as a mechanism for widespread co-occurring histone acetylation marks. CoRec can be readily applied to different cell systems and provides a powerful approach to define TF-COF networks impacting chromatin state and gene regulation.
Accessory proteins increase the efficiency of RNA editing by Arabidopsis chloroplast editosomes
Authors: Lombana Jose , Hanson Maureen R. , Bentolila Stéphane
Published: April 2024

RNA editing modifies cytidines to uridines in plant organelle transcripts so that their sequences differ from the ones predicted from the genomic DNA. This process, conserved across most land plants, involves a family of RNA-binding proteins that has significantly expanded, the pentatricopeptide repeat (PPR)-containing proteins. In angiosperms, PPR proteins are found in editosomes associated with accessory proteins. The exact function of these accessory proteins has been unclear. Bacterial co-expression of an angiosperm synthetic factor and different accessory proteins, RIP2, RIP9, ORRM1 demonstrates their essential role in editing of an RNA target. The presence of ORRM1 and RIP2 or ORRM1 and RIP9 in bacteria with the PPR factor results in a target editing extent of 80%, which is similar to what is observedin planta. Accessory proteins increase the affinity of the PPR factor for the target RNA, likely the explanation of their role in improving editing efficiency. RNA-seq analysis of bacterial transcriptome in samples expressing various combinations of accessory proteins with the synthetic factor identified a total of 34 off-target editing events. Investigation of their upstream sequences that are recognized and bound by the synthetic factor allows the optimization of future designs to improve the specificity of this programmable RNA-editing factor.
Ribozyme-mediated gene-fragment complementation for non-destructive reporting of DNA transfer within soil
Authors: Selinidis Malyn A. , Corliss Andrew C. , Chappell James , Silberg Jonathan J.
Published: April 2024

Enzymes that produce volatile metabolites can be coded into genetic circuits to report non-disruptively on microbial behaviors in hard-to-image soils. However, these enzyme reporters remain challenging to apply in gene transfer studies due to leaky off states that can lead to false positives. To overcome this problem, we designed a reporter that uses ribozyme-mediated gene-fragment complementation of a methyl halide transferase (MHT) to regulate the synthesis of methyl halides. We split themhtgene into two non-functional fragments and attached these to a pair of splicing ribozyme fragments. While the individualmht-ribozyme fragments did not produce methyl halides when transcribed alone inEscherichia coli, co-expression resulted in a spliced transcript that translated the MHT reporter. When cells containing onemht-ribozyme fragment transcribed from a mobile plasmid were mixed with cells that transcribed the secondmht-ribozyme fragment, methyl halides were only detected following rare conjugation events. When conjugation was performed in soil, it led to a 16-fold increase in methyl halides in the soil headspace. These findings show how ribozyme-mediated gene-fragment complementation can achieve tight control of protein reporter production, a level of control that will be critical for monitoring the effects of soil conditions on gene transfer and the fidelity of biocontainment measures developed for environmental applications.
NaV1.7 targeted fluorescence imaging agents for nerve identification during intraoperative procedures
Authors: Gonzales Junior , Adilbay Dauren , de Souza Franca Paula Demetrio , Artschwager Raik , Chow Chun Yuen , Viray Tara , Johnson Delissa S. , Jiang Yan , Patel Snehal G. , Ganly Ian , Schroeder Christina I. , Lewis Jason S. , King Glenn F. , Reiner Thomas , Pillarsetty Nagavarakishore
Published: April 2024

Surgeries and trauma result in traumatic and iatrogenic nerve damage that can result in a debilitating condition that approximately affects 189 million individuals worldwide. The risk of nerve injury during oncologic surgery is increased due to tumors displacing normal nerve location, blood turbidity, and past surgical procedures, which complicate even an experienced surgeon’s ability to precisely locate vital nerves. Unfortunately, there is a glaring absence of contrast agents to assist surgeons in safeguarding vital nerves. To address this unmet clinical need, we leveraged the abundant expression of the voltage-gated sodium channel 1.7 (NaV1.7) as an intraoperative marker to access peripheral nervesin vivo, and visualized nerves for surgical guidance using a fluorescently-tagged version of a potent NaV1.7-targeted peptide, Tsp1a, derived from a Peruvian tarantula. We characterized the expression of NaV1.7 in sensory and motor peripheral nerves across mouse, primate, and human specimens and demonstrated universal expression. We synthesized and characterized a total of 10 fluorescently labeled Tsp1a-peptide conjugates to delineate nerves. We tested the ability of these peptide-conjugates to specifically accumulate in mouse nerves with a high signal-to-noise ratioin vivo. Using the best-performing candidate, Tsp1a-IR800, we performed thyroidectomies in non-human primates and demonstrated successful demarcation of the recurrent laryngeal and vagus nerves, which are commonly subjected to irreversible damage. The ability of Tsp1a to enhance nerve contrast during surgery provides opportunities to minimize nerve damage and revolutionize standards of care across various surgical specialties.
Brain dynamics and spatiotemporal trajectories during threat processing
Authors: Misra Joyneel , Pessoa Luiz
Published: April 2024

In the past decades, functional MRI research has investigated task processing in a largely static fashion based on evoked responses during blocked and event-related designs. Despite some progress in naturalistic designs, our understanding of threat processing remains largely limited to those obtained with standard paradigms with limited dynamics. In the present paper, we applied Switching Linear Dynamical Systems to uncover the dynamics of threat processing during a continuous threat-of-shock paradigm. First, we demonstrated that the SLDS model learned the regularities of the experimental paradigm, such that states and state transitions estimated from fMRI time series data from 85 regions of interest reflected threat proximity and threat approach vs. retreat. After establishing that the model captured key properties of threat-related processing, we characterized the dynamics of the states and their transitions. Importantly, we characterized both endogenous and exogenous contributions to dynamics. The results revealed how threat processing can be viewed in terms of dynamic multivariate patterns whose trajectories are a combination of intrinsic and extrinsic factors that jointly determine how the brain temporally evolves during dynamic threat. Furthermore, we developed a measure ofregion importancethat quantifies the contributions of an individual brain region to system dynamics, which complements the system-level characterization that is obtained with the state-space SLDS formalism. Finally, we investigated the generalizability of the modeling approach. The successful application of the SLDS model trained on one paradigm to a separate experiment illustrates the potential of this approach to capture fMRI dynamics that generalize across related but distinct threat-processing tasks. We propose that viewing threat processing through the lens of dynamical systems offers important avenues to uncover properties of the dynamics of threat that are not unveiled with standard experimental designs and analyses.
Hierarchical determinants of the oxidation-induced mutational landscape in human cells
Authors: Cordero Cameron , Mehta Kavi P. M. , Weaver Tyler M. , Ling Justin A. , Freudenthal Bret D. , Cortez David , Roberts Steven A.
Published: April 2024

8-oxoguanine (8-oxoG) is a common oxidative DNA lesion, which causes G>T substitutions that compose COSMIC single base substitution signature 18 (SBS18) in human cancers. Determinants of local and regional differences in 8-oxoG-induced mutability are currently unknown. To uncover factors influencing the topology of 8-oxoG-induced mutations, we assessed spontaneous and KBrO3-induced 8-oxoG mutagenesis in human cell lines. KBrO3exposure produced a SBS18-like substitution spectrum and a distinct never-before reported INDEL signature that we also observed in human cancers. KBrO3-induced 8-oxoG lesions occurred with similar sequence preference as KBrO3-induced substitutions, indicating that the reactivity of specific reactive oxygen species (ROS) dictates the trinucleotide motif specificity for 8-oxoG-induced mutagenesis. While 8-oxoG lesions occurred relatively uniformly across chromatin states and nucleosomes, 8-oxoG-induced mutations occurred more frequently in more compact regions of the genome, within nucleosomal DNA, and at inward facing guanines within strongly positioned nucleosomes. Cryo-EM structures of OGG1 bound to nucleosomes indicate that these effects originate from OGG1’s ability to flip outward positioned 8-oxoG lesions into the catalytic pocket with only minor alterations to nucleosome structure, while inward facing lesions occluded by the histone octamer are unrecognized. Mutation spectra from cells with DNA repair deficiencies revealed a hierarchical DNA repair network limiting 8-oxoG mutagenesis in human cells, where OGG1– and MUTY-mediated BER is supplemented by replication-associated factors participating in tolerance of 8-oxoG or derived repair intermediates (i.e. Pol η and HMCES). Surprisingly, analysis of transcriptional asymmetry of KBrO3-induced mutations demonstrated transcription-coupled repair of 8-oxoG in Pol η-deficient cells. Thus, radical chemistry, chromatin structures, and DNA repair processes combine to dictate the oxidative mutational landscape in human genomes.
Profiling the intestinal microbiota, plasma bile acids and inflammation markers reveals novel associations in Crohn’s disease and Ulcerative colitis
Authors: Prast-Nielsen Stefanie , Granström Anna Löf , Kiasat Ali , Ahlström Gustav , Edfeldt Gabriella , Rautiainen Susanne , Boulund Fredrik , Andersson Fredrik O , Lindberg Johan , Schuppe-Koistinen Ina , Gustafsson Ulf O , Engstrand Lars
Published: April 2024

Background and aims

Our study explores signatures for Crohn’s disease (CD) and Ulcerative Colitis (UC) reflecting the interplay between the intestinal microbiota, systemic inflammation, and plasma bile acid homeostasis.

Methods

1,257 individuals scheduled for colonoscopy were included and completed a comprehensive questionnaire. Individuals with IBD (‘CD’ n=64 and ‘UC’ n= 55), were age– and gender-matched to controls without findings during colonoscopy. Taxonomic profiles of the fecal microbiota and plasma profiles of inflammatory proteins and bile acids were used to build disease classifiers. Omics integration identified associations across datasets.

Results

B. hydrogenotrophicawas associated with CD andC. eutactus, C. sp. CAG 167, B. cellulosilyticus, C. mitsuokaiwith controls. Ten inflammation markers were increased in CD, and eleven bile acids and derivatives were decreased in CD, while 7a-Hydroxy-3-oxo-4-cholestenoate (7-HOCA) and chenodeoxycholic acid (CDCA) were increased compared to controls.

In UC, commensals such asF. prausnitziiandA. muciniphilawere depleted. CCL11, IL-17A, and TNF were increased in UC and associated to gut microbial changes. Correlations between taxa and bile acids were all positive.

Conclusions

For both CD and UC, taxonomic differences were primarily characterized by a reduction in commensal gut microbes which exhibited positive correlations with secondary bile acids and negative correlations with inflammation markers, potentially reflecting protective mechanisms of these commensal microbes.
Spatially Enhanced Processing for Valuable Objects in Prefrontal Cortex Neurons During Efficient Search
Authors: Sharifi Kiomars , Abbaszadeh Mojtaba , Ghazizadeh Ali
Published: April 2024

It is recently shown that objects with long-term reward associations can be efficiently located during visual search. The neural mechanism for valuable object pop-out is unknown. In this work, we recorded neuronal responses in the ventrolateral prefrontal cortex (vlPFC) with known roles in visual search and reward processing in macaques while monkeys engaged in efficient vs inefficient visual search for high-value fractal objects (targets). Behavioral results and modeling using multi-alternative attention-modulated drift-diffusion (MADD) indicated that efficient search was concurrent with enhanced processing for peripheral objects. Notably, neural results showed response amplification and receptive field widening to peripherally presented targets in vlPFC during visual search. Both neural effects predict higher target detection and were found to be correlated with it. Our results suggest that value-driven efficient search independent of low-level visual features arises from reward-induced spatial processing enhancement of peripheral valuable objects.
Exploring Gene-Mediated Mechanisms Behind Shared Phenotypes Across Diverse Diseases Using the clGENE Tool
Authors: Zheng Li
Published: April 2024

The observation of similar clinical characteristics across a broad spectrum of diseases suggests the existence of underlying shared molecular mechanisms. Identifying these mechanisms is critical for uncovering the molecular roots of diseases and advancing the development of innovative therapeutic strategies. However, researching the common genes that mediate similar phenotypes among different diseases often requires the integration of various sequencing datasets and clinical data. The batch effects among these datasets and the complexity of clinical data present significant challenges to the research. This study developed a framework named “clGENE”, aimed at uncovering the molecular mechanisms behind similar phenotypes across different diseases. By integrating data normalization, cosine similarity analysis, and principal component analysis (PCA) algorithms, this framework is capable of effectively identifying shared molecular mechanisms associated with specific phenotypes and further selecting key shared genes. Through the analysis of a pan-cancer dataset, we have verified the efficacy and reliability of the “clGENE” framework. Furthermore, this study also established a dataset on immune cell infiltration and successfully identified key patterns of immune cell infiltration in different cancer lymph node metastasis stages using the ‘clGENE’ framework, further confirming its potential application in biomedical research.
Sex differences in oxycodone-taking behaviors are linked to disruptions in reward-guided, decision-making functions
Authors: LaRocco Kaitlyn , Villiamma Peroushini , Hill Justin , Russell Mara A. , DiLeone Ralph J. , Groman Stephanie M.
Published: April 2024

Problematic opioid use that emerges in a subset of individuals may be due to pre-existing disruptions in the biobehavioral mechanisms that regulate drug use. The identity of these mechanisms is not known, but emerging evidence suggests that suboptimal decision-making that is observable prior to drug use may contribute to the pathology of addiction and, notably, serve as a powerful phenotype for interrogating biologically based differences in opiate-taking behaviors. The current study investigated the relationship between decision-making phenotypes and opioid-taking behaviors in male and female Long Evans rats. Adaptive decision-making processes were assessed using a probabilistic reversal-learning task and oxycodone- (or vehicle, as a control) taking behaviors assessed for 32 days using a saccharin fading procedure that promoted dynamic intake of oxycodone. Tests of motivation, extinction, and reinstatement were also performed. Computational analyses of decision-making and opioid-taking behaviors revealed that attenuated reward-guided decision-making was associated with greater self-administration of oxycodone and addiction-relevant behaviors. Moreover, pre-existing impairments in reward-guided decision-making observed in female rats was associated with greater oxycodone use and addiction-relevant behaviors when compared to males. These results provide new insights into the biobehavioral mechanisms that regulate opiate-taking behaviors and offer a novel phenotypic approach for interrogating sex differences in addiction susceptibility and opioid use disorders.
Heterologous expression and purification of glutamate decarboxylase-1 from the model plantArabidopsis thaliana: characterization of the enzyme’sin vitrotruncation by thiol endopeptidase activity
Authors: Menard Brittany S. , Benidickson Kirsten H. , Raytek Lee Marie , Snedden Wayne A. , Plaxton William C.
Published: April 2024

Plant glutamate decarboxylase (GAD) is a Ca2+-calmodulin activated cytosolic enzyme that produces γ-aminobutyrate (GABA) as the first committed step of the GABA shunt. This pathway circumvents the 2-oxoglutarate to succinate reactions of the mitochondrial tricarboxylic acid cycle. Our prior research established thatin vivophosphorylation of the root-specific AtGAD1 isozyme (AT5G17330) occurs at multiple N-terminal serine residues, following Pi resupply to Pi-starved cell cultures of the model plantArabidopsis thaliana. The aim of the current investigation was to purify recombinant AtGAD1 following its expression inEscherichia colito facilitate studies of the impact of site-specific phosphorylation on its kinetic properties. However,in vitroproteolytic truncation of a 5 kDa polypeptide from the C-terminus of 59 kDa AtGAD1 subunits occurred during its purification. Immunoblotting demonstrated that most protease inhibitors or cocktails that we tested were ineffective in suppressing partial AtGAD1 proteolysis during incubation of clarified extracts at 23 °C. Although the thiol modifiers N-ethylmaleimide or 2,2-dipyridyl disulfide negated AtGAD1 proteolysis, they also abolished its GAD activity. This indicates that an essential -SH group is needed for catalytic activity, and that AtGAD1 is susceptible to partial degradation either by anE. colicysteine endopeptidase, or possibly via autoproteolytic activity. The inclusion of exogenous Ca2+/calmodulin in extraction and chromatography buffers facilitated the purification of non-proteolyzed AtGAD1 to a specific activity of 27 (µmol GABA produced/mg) at optimal pH 5.8, while exhibiting an approximate 3-fold activation by Ca2+/CaM at pH 7.3. By contrast, the purified partially proteolyzed His6-AtGAD1 was >40% less active at both pH values, and only activated 2-fold by Ca2+/CaM at pH 7.3. These results emphasize the need to diagnose and prevent unwanted proteolysis before conducting kinetic studies of purified regulatory enzymes.
Exploring Lee-Yang and Fisher zeros in the 2D Ising model through multipoint Padé approximants
Authors: Singh Simran , Cipressi Massimo , Di Renzo Francesco
Published: April 2024

We present a numerical calculation of the Lee-Yang and Fisher zeros of the 2D Ising model using multipoint Padé approximants. We perform simulations for the 2D Ising model with ferromagnetic couplings both in the absence and in the presence of a magnetic field using a cluster spin-flip algorithm. We show that it is possible to extract genuine signature of Lee-Yang and Fisher zeros of the theory through the poles of magnetization and specific heat, using the multipoint Padé method. We extract the poles of magnetization using Padé approximants and compare their scaling with known results. We verify the circle theorem associated to the well known behavior of Lee-Yang zeros. We present our finite volume scaling analysis of the zeros done at T=Tc for a few lattice sizes, extracting to a good precision the (combination of) critical exponents βδ. The computation at the critical temperature is performed after the latter has been determined via the study of Fisher zeros, thus extracting both βc and the critical exponent ν. Results already exist for extracting the critical exponents for the Ising model in two and three dimensions making use of Fisher and Lee-Yang zeros. In this work, multipoint Padé is shown to be competitive with this respect and thus a powerful tool to study phase transitions.

Published by the American Physical Society
2024
Neutrino fog for dark matter-electron scattering experiments
Authors: Carew Ben , Caddell Ashlee R. , Maity Tarak Nath , O’Hare Ciaran A. J.
Published: April 2024

The search for sub-GeV dark matter via scattering on electrons has ramped up in the last few years. Like in the case of dark matter scattering on nuclei, electron-recoil-based searches also face an ultimate background in the form of neutrinos. The so-called “neutrino fog” refers to the range of open dark matter parameter space where the background of neutrinos can potentially prevent a conclusive discovery claim of a dark matter signal from being made. In this study, we map the neutrino fog for a range of electron recoil experiments based on silicon, germanium, xenon, and argon targets. In analogy to the nuclear recoil case, we also calculate the “edge” to the neutrino fog, which can be used as a visual guide to determine where neutrinos become an important background—this boundary excludes some parts of the key theory milestones used to motivate these experiments.

Published by the American Physical Society
2024
Synthesis and crystal structure of an iron triazole complex resulting from the unexpected ligand cleavage of a triazolium carbene precursor
Authors: Pacholski Roman , Durka Krzysztof , Buchalski Piotr
Published: April 2024

Typically reactions of N-heterocyclic carbenes with transition metals are straightforward and require a carbene salt, a base strong enough to deprotonate such a salt and a metal. Yet when carbene precursors are in the form of triazolium salts, reaction may not proceed as easily as expected. In our work, we intended to obtain a triazolylidene complex of iron(II) chloride, but due to the presence of small amounts of water in the tetrahydrofuran solvent used, bis(acetonitrile)tetrakis(1-benzyl-1H-1,2,4-triazole-κN
4)iron(II) μ-oxido-bis[trichloridoferrate(III)] acetonitrile disolvate, [Fe(C9H9N3)4(CH3CN)2][Fe2Cl6O]·2CH3CN – an interesting anion with a linear geometry of the O atom – was formed instead of the iron carbene complex. Reaction proceeded via cleavage of the alkyl N-substituent of the triazolium salt. The formation of the product was confirmed by X-ray crystallography. The crystal structure and possible reaction pathways are discussed.
STOPGAP: an open-source package for template matching, subtomogram alignment and classification
Authors: Wan William , Khavnekar Sagar , Wagner Jonathan
Published: April 2024

Cryo-electron tomography (cryo-ET) enables molecular-resolution 3D imaging of complex biological specimens such as viral particles, cellular sections and, in some cases, whole cells. This enables the structural characterization of molecules in their near-native environments, without the need for purification or separation, thereby preserving biological information such as conformational states and spatial relationships between different molecular species. Subtomogram averaging is an image-processing workflow that allows users to leverage cryo-ET data to identify and localize target molecules, determine high-resolution structures of repeating molecular species and classify different conformational states. Here, STOPGAP, an open-source package for subtomogram averaging that is designed to provide users with fine control over each of these steps, is described. In providing detailed descriptions of the image-processing algorithms that STOPGAP uses, this manuscript is also intended to serve as a technical resource to users as well as for further community-driven software development.
Reducing airline accident risk and saving lives: financial health, corporate governance, and aviation safety
Authors: Khadivar Hamed , Murphy Miles , Walker Thomas
Published: April 2024

Purpose

This study investigates the impact of financial health and corporate governance on aviation safety, aiming to fill a critical gap in existing research. The purpose of this study is to identify how these factors influence the safety records of airlines and provide insights for regulators, airlines and stakeholders to enhance aviation safety.

Design/methodology/approach

Using a comprehensive international sample spanning 1950–2009 and later, this empirical analysis draws on diverse databases. The authors examine 372 airlines across 70 countries from 1990 to 2016. The research uses statistical models to analyze the relationship between financial indicators, corporate governance quality and aviation safety, addressing limitations of prior single-country studies.

Findings

The findings reveal a significant inverse relationship between financial health and accident propensity, with profitable airlines exhibiting lower accident rates. Additionally, airlines with higher corporate governance quality, characterized by qualified directors and stable leadership, experience fewer accidents. The study identifies key factors such as pilot errors, mechanical failures and adverse weather, contributing to approximately 75% of accidents, emphasizing the importance of organizational control.

Practical implications

This research has crucial implications for aviation safety policies and practices. Regulators and international organizations, such as International Civil Aviation Organization and International Air Transport Association, should allocate resources to supervise financially vulnerable airlines and those with lower governance quality. Governments might consider incentivizing safety practices through tax deductibility for relevant expenses. Shareholders are encouraged to prioritize qualified, younger and less busy directors, recognizing their impact on safety performance.

Originality/value

This study contributes to existing literature by addressing methodological biases and offering a comprehensive international perspective. The identification of a link between financial health, corporate governance and accident rates in the aviation industry provides valuable insights. The research informs policymakers, regulators and industry stakeholders on effective strategies to improve safety by considering financial and governance factors under their control.
A comparative analysis of lean start-up and design thinking and its integration
Authors: Sreenivasan Aswathy , Suresh M.
Published: April 2024

Purpose

This study aims to emphasize the integration of lean start-up and design thinking approaches and investigate how they may be used together.

Design/methodology/approach

The report uses a systematic literature review methodology to analyze and summarize previous research on combining lean start-up and design thinking. Inferences were discovered and analyzed after relevant publications were chosen based on predetermined inclusion criteria.

Findings

The research shows that combining lean start-up and design thinking significantly impacts entrepreneurship. Start-ups can efficiently uncover consumer needs, reduce risks and improve their product or service offerings by combining the client-centricity of design thinking with the iterative and data-driven concepts of lean start-up. This integration promotes an innovative culture, gives teams the freedom to try new things and learn from mistakes and raises the possibility of start-up success.

Research limitations/implications

The dependence on pre-existing literature, which might cover only some potential uses and circumstances, is a weakness of this research. It is advised that more empirical research be conducted to determine the precise circumstances in which the integrated strategy performs best. Future studies should also explore the difficulties and drawbacks of using these approaches to offer suggestions for overcoming them and maximizing their advantages.

Practical implications

The findings have significant ramifications for business owners and other professionals working in the start-up environment. The combination of lean start-up and design thinking emphasizes the relevance of early customer interaction and empathy-driven design. To foster creativity and hasten the expansion of start-ups, practitioners are urged to create a comprehensive strategy that integrates the advantages of both techniques. Through this integration, business owners may develop solutions that appeal to their target market, increasing adoption rates and market competitiveness.

Originality/value

This study is interesting in comparing lean start-up and design thinking, emphasizing the overlaps and benefits of their application to entrepreneurship. This study discusses successful start-up methods by offering suggestions for future research and practice. It also provides a basis for further developing and adopting the integrated approach.
Extended service strategy choice for competing manufacturers in agency retail platform considering consumer preferences
Authors: Liu Bin , Sun Jing , Huang Zongsheng
Published: April 2024

Purpose

We investigate the extended service strategy choices of competing manufacturers and examine their impact on the retail platform.

Design/methodology/approach

We construct a supply chain model with a retail platform as the leader and manufacturers as the followers. Manufacturers face differential consumer preferences on the same agency retail platform, and they can sell a bundled extended service product and sell a separate product without any extended service.

Findings

The sale of extended warranty services on the retail platform leads to lower pricing of the manufacturers' products and changes in the product market structure in response to differences in consumer preferences. The retailing platform tends to provide an extended warranty conditionally. The sale of extended warranty services on a retail platform would be detrimental to the interests of the manufacturer who sells products with extended warranty services and in favor of the manufacturer who sells products without them.

Originality/value

The equilibrium results of the retail platform’s non-sales and sales of extended warranty services for the no-extended warranty product under the same commission rate and differential commission rate models are discussed, and the product structure of the market is investigated, respectively.
Application of deep learning model incorporating domain knowledge in international migration forecasting
Authors: Pu Tongzheng , Huang Chongxing , Zhang Haimo , Yang Jingjing , Huang Ming
Published: April 2024

Purpose

Forecasting population movement trends is crucial for implementing effective policies to regulate labor force growth and understand demographic changes. Combining migration theory expertise and neural network technology can bring a fresh perspective to international migration forecasting research.

Design/methodology/approach

This study proposes a conditional generative adversarial neural network model incorporating the migration knowledge – conditional generative adversarial network (MK-CGAN). By using the migration knowledge to design the parameters, MK-CGAN can effectively address the limited data problem, thereby enhancing the accuracy of migration forecasts.

Findings

The model was tested by forecasting migration flows between different countries and had good generalizability and validity. The results are robust as the proposed solutions can achieve lesser mean absolute error, mean squared error, root mean square error, mean absolute percentage error and R2 values, reaching 0.9855 compared to long short-term memory (LSTM), gated recurrent unit, generative adversarial network (GAN) and the traditional gravity model.

Originality/value

This study is significant because it demonstrates a highly effective technique for predicting international migration using conditional GANs. By incorporating migration knowledge into our models, we can achieve prediction accuracy, gaining valuable insights into the differences between various model characteristics. We used SHapley Additive exPlanations to enhance our understanding of these differences and provide clear and concise explanations for our model predictions. The results demonstrated the theoretical significance and practical value of the MK-CGAN model in predicting international migration.
Swimming against the current: the positive effects of counter-cultural HR practices on the calculative/collaborative HR practices–firm performance relationship
Authors: Prince Nicholas R. , Prince J. Bruce , Prince Sari N. , Kabst Rüediger
Published: April 2024

Purpose

This paper investigates the effect of counter-cultural human resources (CCHR) practices on firm performance. Specifically, it investigates the impact of national culture [future orientation (FO), in-group collectivism (I-GC), performance orientation (PO), power distance (PD) and uncertainty avoidance (UA)] on the calculative and collaborative HR practice–firm performance relationship.

Design/methodology/approach

This study uses data from the CRANET and GLOBE studies to conduct a multi-level analysis of the impact of national culture on the calculative/collaborative HR–firm performance relationship.

Findings

It finds support for both the CCHR and societal-culture fit (SCF) perspectives of national culture, with FO and I-GC supporting the CCHR perspective and the other culture dimensions aligning more closely with SCF.

Originality/value

These findings empirically validate that CCHR practices can help supplement behaviors lacking in the cultural environment in which organizations operate.
Empowering architecture, engineering and construction students through building information modeling competitions: a deep dive into behavioral motivation
Authors: Ao Yibin , Peng Panyu , Li Mingyang , Li Jiayue , Wang Yan , Martek Igor
Published: April 2024

Purpose

Building Information Modeling (BIM) competitions are a beneficial approach to enhance BIM education, offering students practical experience in BIM application, including mastering workflows and technical tools. However, research exploring the individual perceptions influencing participation intentions and behaviors in BIM competitions is limited. Therefore, this study aims to investigate the factors affecting university students' behavioral intention and behavior in BIM competitions, providing theoretical support for BIM competitions and educational reform.

Design/methodology/approach

This study employs the Structural Equation Modeling (SEM) based on the Unified Theory of Acceptance and Use of Technology (UTAUT) framework to analyze the factors influencing BIM competition participation among 970 Architecture, Engineering, and Construction (AEC) university students.

Findings

The results of the study show that social influence, attitude, and self-efficacy play critical roles in shaping students' intentions to participate in BIM competitions. Furthermore, self-efficacy, facilitating conditions, and behavioral intention significantly influence students' actual engagement in such competitions. Surprisingly, effort expectancy negatively influences intentions, as less challenging tasks can lead students to perceive their participation as less impactful on their skills and learning, reducing their behavioral intention to participate.

Originality/value

This research provides valuable insights into the effectiveness of BIM competitions in enhancing BIM education for AEC students. Extending the UTAUT model to include self-efficacy and attitude, provides a novel perspective for understanding students' intentions and behaviors regarding BIM competitions. The study’s theoretical support proposes incorporating BIM competitions to augment BIM teaching methods and offers suggestions for advancing the efficacy of students' involvement in BIM competitions within higher education, thus contributing to educational reform in the AEC sector.
Caught in crises: Syrian refugees in Türkiye’s labor market
Authors: Mohammed Umar
Published: April 2024

Purpose

This study aims to analyze the factors driving Syrian refugees into the informal labor market in Türkiye despite the existence of regulations and programs to facilitate their integration into the formal labor market.

Design/methodology/approach

This study presents results from a literature review of secondary sources and primary data collection through semi-structured interviews with key stakeholders and Syrian refugees.

Findings

The study shows that the implementation of policies and programs to boost formal employment among refugees has yielded limited results. Many refugees continue to operate within the informal economy. This informality is due to various socio-economic challenges, including anti-refugee sentiments, geographical restrictions and economic crises. The 2023 twin earthquakes have further exacerbated the vulnerable situation of refugees, intensifying the difficulty of achieving self-reliance.

Research limitations/implications

The study’s drawbacks include a small sample size. This implies that the sample is not representative; therefore, results may lack generalizability.

Practical implications

The study’s findings could stimulate greater engagement in public policy, facilitate the management of public perceptions regarding refugees and provide support to the private sector, all to enhance the integration of Syrian refugees into the formal labor market.

Originality/value

This study addresses crucial areas previously unexplored, including the impact of economic and natural disaster crises on the labor market integration of refugees. To the best of the author’s knowledge, by investigating these factors for the first time, this study offers novel insights into their influence on refugees’ labor market integration.