bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing the accuracy of single-molecule data analysis using tMAVEN
Authors: Verma Anjali R. , Ray Korak Kumar , Bodick Maya , Kinz-Thompson Colin D. , Gonzalez Ruben L.
Published: August 2023

Time-dependent single-molecule experiments contain rich kinetic information about the functional dynamics of biomolecules. A key step in extracting this information is the application of kinetic models, such as hidden Markov models (HMMs), which characterize the molecular mechanism governing the experimental system. Unfortunately, researchers rarely know the physico-chemical details of this molecular mechanisma priori, which raises questions about how to select the most appropriate kinetic model for a given single-molecule dataset and what consequences arise if the wrong model is chosen. To address these questions, we have developed and used time-seriesModeling,Analysis, andVisualizationENvironment (tMAVEN), a comprehensive, open-source, and extensible software platform. tMAVEN can perform each step of the single-molecule analysis pipeline, from pre-processing to kinetic modeling to plotting, and has been designed to enable the analysis of a single-molecule dataset with multiple types of kinetic models. Using tMAVEN, we have systematically investigated mismatches between kinetic models and molecular mechanisms by analyzing simulated examples of prototypical single-molecule datasets exhibiting common experimental complications, such as molecular heterogeneity, with a series of different types of HMMs. Our results show that no single kinetic modeling strategy is mathematically appropriate for all experimental contexts. Indeed, HMMs only correctly capture the underlying molecular mechanism in the simplest of cases. As such, researchers must modify HMMs using physico-chemical principles to avoid the risk of missing the significant biological and biophysical insights into molecular heterogeneity that their experiments provide. By enabling the facile, side-by-side application of multiple types of kinetic models to individual single-molecule datasets, tMAVEN allows researchers to carefully tailor their modeling approach to match the complexity of the underlying biomolecular dynamics and increase the accuracy of their single-molecule data analyses.

Statement of Significance

The power of time-dependent single-molecule biophysical experiments lies in their ability to uncover the molecular mechanisms governing experimental systems by computationally applying kinetic models to the data. While many software solutions have been developed to estimate the optimal parameters of such models, the results reported here show that the models themselves are often inherently mismatched with the molecular mechanisms they are being used to analyze. To investigate these mismatches and demonstrate how to best model the kinetics of a molecular mechanism, we have used time-seriesModeling,Analysis, andVisualizationENvironment (tMAVEN), an open-source software platform we have developed that, among other features, enables the analysis of single-molecule datasets using different kinetic models within a single, extensible, and customizable pipeline.
Bacteriophage P22 SieA mediated superinfection exclusion
Authors: Leavitt Justin C. , Woodbury Brianna M. , Gilcrease Eddie B. , Bridges Charles M. , Teschke Carolyn M. , Casjens Sherwood R.
Published: August 2023

Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages.Salmonellaphage P22 has four such systems that are expressed from the prophage in a lysogen that are encoded by thec2(repressor),gtrABC,sieA, andsieBgenes. Here we report that the P22-encoded SieA protein is the only phage protein required for exclusion by the SieA system, and that it is an inner membrane protein that blocks DNA injection by P22 and its relatives, but has no effect on infection by other tailed phage types. The P22 virion injects its DNA through the host cell membranes and periplasm via a conduit assembled from three “ejection proteins” after their release from the virion. Phage P22 mutants were isolated that overcome the SieA block, and they have amino acid changes in the C-terminal regions of the gene16and20encoded ejection proteins. Three different single amino acid changes in these proteins are required to obtain nearly full resistance to SieA. Hybrid P22 phages that have phage HK620 ejection protein genes are also partially resistant to SieA. There are three sequence types of extant phage-encoded SieA proteins that are less than 30% identical to one another, yet comparison of two of these types found no differences in target specificity. Our data are consistent with a model in which the inner membrane protein SieA interferes with the assembly or function of the periplasmic gp20 and membrane-bound gp16 DNA delivery conduit.

HIGHLIGHTS

Phage P22 SieA protein blocks DNA injection by P22-like phages

SieA is an inner membrane protein

Hybrid P22 phages with phage HK620 ejection proteins partially escape SieA exclusion

SieA escape mutants of P22 alter the gp16 and 20 proteins that form the DNA ejection tube.
The α-crystallin chaperones undergo a quasi-ordered co-aggregation process in response to saturating client interaction
Authors: Miller Adam P. , O’Neill Susan E. , Lampi Kirsten J. , Reichow Steve L.
Published: August 2023

Small heat shock proteins (sHSPs) are ATP-independent chaperones vital to cellular proteostasis, preventing protein aggregation events linked to various human diseases including cataract. The α-crystallins, αA-crystallin (αAc) and αB-crystallin (αBc), represent archetypal sHSPs that exhibit complex polydispersed oligomeric assemblies and rapid subunit exchange dynamics. Yet, our understanding of how this plasticity contributes to chaperone function remains poorly understood. This study investigates structural changes in αAc and αBc during client sequestration under varying degree of chaperone saturation. Using biochemical and biophysical analyses combined with single-particle electron microscopy (EM), we examined αAc and αBc in their apo-states and at various stages of client-induced co-aggregation, using lysozyme as a model client. Quantitative single-particle analysis unveiled a continuous spectrum of oligomeric states formed during the co-aggregation process, marked by significant client-triggered expansion and quasi-ordered elongation of the sHSP scaffold. These structural modifications culminated in an apparent amorphous collapse of chaperone-client complexes, resulting in the creation of co-aggregates capable of scattering visible light. Intriguingly, these co-aggregates maintain internal morphological features of highly elongated sHSP scaffolding with striking resemblance to polymeric α-crystallin species isolated from aged lens tissue. This mechanism appears consistent across both αAc and αBc, albeit with varying degrees of susceptibility to client-induced co-aggregation. Importantly, our findings suggest that client-induced co-aggregation follows a distinctive mechanistic and quasi-ordered trajectory, distinct from a purely amorphous process. These insights reshape our understanding of the physiological and pathophysiological co-aggregation processes of sHSPs, carrying potential implications for a pathway toward cataract formation.
Combined PI3K and MAPK inhibition synergizes to suppress PDAC
Authors: Bye Bailey A. , Jack Jarrid , Pierce Alexandra , Walsh R. McKinnon , Eades Austin , Chalise Prabhakar , Olou Appolinaire , VanSaun Michael N.
Published: August 2023

Oncogenic KRAS mutations are nearly ubiquitous in pancreatic ductal adenocarcinoma (PDAC), yet therapeutic attempts to target KRAS as well as its target MAPK pathway effectors have shown limited success due to the difficulty to pharmacologically target KRAS, inherent drug resistance in PDAC cells, and acquired resistance through activation of alternative mitogenic pathways such JAK-STAT and PI3K-AKT. While KRAS canonically drives the MAPK signaling pathway via RAF-MEK-ERK, it is also known to play a role in PI3K-AKT signaling. Our therapeutic study targeted the PI3K-AKT pathway with the drug Omipalisib (p110α/β/δ/γ and mTORC1/2 inhibitor) in combination with MAPK pathway targeting drug Trametinib (MEK1/2 inhibitor) or SHP099-HCL (SHP099), which is an inhibitor of the KRAS effector SHP2. Western blot analysis demonstrated that application of Trametinib or SHP099 alone selectively blocked ERK phosphorylation (pERK) but failed to suppress phosphorylated AKT (pAKT) and in some instances increased pAKT levels. Conversely, Omipalisib alone successfully inhibited pAKT but failed to suppress pERK. Therefore, we hypothesized that a combination therapeutic comprised of Omipalisib with either Trametinib or SHP099 would inhibit two prominent mitogenic pathways, MEK and PI3K-AKT, to more effectively suppress pancreatic cancer.In vitrostudies demonstrated that both Omipalisib/Trametinib and Omipalisib/SHP099 combination therapeutic strategies were generally more effective than treatment with each drug individually at reducing proliferation, colony formation, and cell migration compared to vehicle controls. Additionally, we found that while combination Omipalisib/SHP099 treatment reduced implanted tumor growthin vivo, the Omipalisib/Trametinib treatment was significantly more effective. Therefore, we additionally tested the Omipalisib/Trametinib combination therapeutic in the highly aggressive PKT (Ptf1acre, LSL-KrasG12D, TGFbR2fl/fl) spontaneous mouse model of PDAC. We subsequently found that PKT mice treated with the Omipalisib/Trametinib combination therapeutic survived significantly longer than mice treated with either drug alone, and more than doubled the mean survival time of vehicle control mice. Altogether, our data support the importance of a dual treatment strategy targeting both MAPK and PI3K-AKT pathways.
Robust and resource-optimal dynamic pattern formation of Min proteinsin vivo
Authors: Ren Ziyuan , Weyer Henrik , Würthner Laeschkir , Li Dongyang , Sou Cindy , Villarreal Daniel , Frey Erwin , Jun Suckjoon
Published: August 2023

The Min system inEscherichia coliplays a crucial role in cellular reproduction by preventing minicell formation through pole-to-pole oscillations. Despite extensive research, predicting the onset of Min protein concentrations for oscillation and understanding the system’s robustness under physiological perturbations remains challenging. Our study aims to address these gaps. We show that the Min system’s dynamic pattern formation is robust across a wide range of Min protein levels and varying growth physiology. Using genetically engineeredE. colistrains, we independently modulated the expression ofminCDandminEinE. coliunder both fast and slow growth conditions. This led to the construction of a MinD-MinE phase diagram, which revealed not just a large oscillation regime but also complex dynamic patterns such as traveling and standing waves. Interestingly, we found that the natural expression level of Min proteins is nearly optimal. Our work combines experimental findings with biophysical theory based on reaction-diffusion models, reproducing the experimental phase diagram and other key properties quantitatively. This includes the observation of an invariant wavelength of dynamic Min patterns across our phase diagram. Crucially, the success of our model depends on the switching of MinE between its latent and active states, indicating its essential role as a robustness module for Min oscillationin vivo. Our results underline the potential of integrating quantitative cell physiology and biophysical modeling in understanding the fundamental mechanisms controlling cell division machinery, offering insights applicable to other biological processes.
SCALiR: a web application for automating absolute quantification of mass spectrometry-based metabolomics data
Authors: Bishop Stephanie L. , Ponce-Alvarez Luis F. , Wacker Soren , Groves Ryan A. , Lewis Ian A.
Published: August 2023

Metabolomics is an important approach for studying complex biological systems. Quantitative liquid chromatography-mass spectrometry (LC-MS)-based metabolomics is becoming a mainstream strategy but presents several technical challenges that limit its widespread use. Computing metabolite concentrations using standard curves generated from standard mixtures of known concentrations is a labor-intensive process which is often performed manually. Currently, there are few options for open-source software tools that can automatically calculate metabolite concentrations. Herein, we introduce SCALiR (Standard Curve Application for determining Linear Ranges), a new web-based software tool specifically built for this task, which allows users to automatically transform LC-MS signal data into absolute quantitative data (https://www.lewisresearchgroup.org/software). The algorithm used in SCALiR automatically finds the equation of the line of best fit for each standard curve and uses this equation to calculate compound concentrations from their LC-MS signal. Using a standard mix containing 77 metabolites, we found excellent correlation between the concentrations calculated by SCALiR and the expected concentrations of each compound (R2= 0.99) and that SCALiR reproducibly calculated concentrations of mid-range standards across ten analytical batches (average coefficient of variation 0.091). SCALiR offers users several advantages, including that it (1) is open-source and vendor agnostic; (2) requires only 10 seconds of analysis time to compute concentrations of >75 compounds; (3) facilitates automation of quantitative workflows; and (4) performs deterministic evaluation of compound quantification limits. SCALiR provides the metabolomics community with a simple and rapid tool that enables rigorous and reproducible quantitative metabolomics studies.
Attentional selection and communication through coherence: Scope and limitations
Authors: Greenwood Priscilla E. , Ward Lawrence M.
Published: August 2023

Synchronous neural oscillations are strongly associated with a variety of perceptual, cognitive, and behavioural processes. It has been proposed that the role of the synchronous oscillations in these processes is to facilitate information transmission between brain areas, the ‘communication through coherence,’ or CTC hypothesis.The details of how this mechanism would work, however, and its causal status, are still unclear. Here we investigate computationally a proposed mechanism for selective attention that directly implicates the CTC as causal. The mechanism involves alpha band (about 10 Hz) oscillations, originating in the pulvinar nucleus of the thalamus, being sent to communicating cortical areas, organizing gamma (about 40 Hz) oscillations there, and thus facilitating phase coherence and communication between them. This is proposed to happen contingent on control signals sent from higher-level cortical areas to the thalamic reticular nucleus, which controls the alpha oscillations sent to cortex by the pulvinar. We studied the scope of this mechanism in parameter space, and limitations implied by this scope, using a computational implementation of our conceptual model. Our results indicate that, although the CTC-based mechanism can account for some effects of top-down and bottom-up attentional selection, its limitations indicate that an alternative mechanism, in which oscillatory coherence is caused by communication between brain areas rather than being a causal factor for it, might operate in addition to, or even instead of, the CTC mechanism.

Author summary

The ability to select some stimulus or stimulus location from all of those available to our senses is critical to our ability to navigate our complex biological and social niche, and to organize appropriate actions to accomplish our goals, namely to survive and to reproduce. We study here a possible mechanism by which the brain could accomplish attentional selection. We show that the interaction between 10 Hz and 40 Hz neural oscillations can provide increases in coherence and information transmission between computationally modelled cortical areas. Our results support the idea that synchronization between oscillations facilitates communication between cortical areas. Limitations and sensitivities to the model, however, also point to the idea that the relation between coherence and communication could go in the opposite direction in some cases, particularly when attention is not involved.
Identification of resistance mechanisms to small-molecule inhibition of TEAD-regulated transcription
Authors: Kulkarni Aishwarya , Mohan Varshini , Tang Tracy T. , Post Leonard , Manning Murray , Thio Niko , Parker Benjamin L. , Rosenbluh Joseph , Vissers Joseph H.A. , Harvey Kieran F.
Published: August 2023

The Hippo tumour suppressor pathway controls transcription by regulating nuclear abundance of YAP and TAZ, which activate transcription with the TEAD1-TEAD4 DNA-binding proteins. Recently, several small-molecule inhibitors of YAP and TEADs have been reported, with some now entering clinical trials for different cancers. Here, we investigated the cellular response to TEAD palmitoylation inhibitors, using a combination of genomic and genetic strategies. Genome-wide CRISPR/Cas9 screens identified genes that modulate the cellular response to TEAD inhibition, including members of the Hippo, MAPK and JAK-STAT signaling pathways. By exploring gene expression programs of mutant cells, we found that MAPK pathway hyperactivation confers resistance to TEAD inhibition by reinstating expression of a subset of YAP/TEAD target genes. Consistent with this, combined inhibition of TEAD and the MAPK protein MEK, synergistically blocked proliferation of several mesothelioma and lung cancer cell lines and more potently reduced the growth of patient-derived lung cancers in vivo. Collectively, we reveal mechanisms by which cells can overcome small-molecule inhibition of TEADs and potential strategies to enhance the anti-tumor activity of emerging Hippo pathway targeted therapies.
Distinct mechanisms by which antioxidant transcription factors Nrf1 and Nrf2 as drug targets contribute to the anticancer efficacy of Cisplatin on hepatoma cells
Authors: Wufuer Reziyamu , Liu Keli , Jingfeng  , Wang Meng , Hu Shaofan , Chen Feilong , Lin Shanshan , Zhang Yiguo
Published: August 2023

Cisplatin (cis-Dichlorodiamineplatinum[II], CDDP) is generally accepted as a platinum-based alkylating agent type of the DNA-damaging anticancer drug, which is widely administrated in clinical treatment of many solid tumors. The pharmacological effect of CDDP is mainly achieved by replacing the chloride ion (Cl−) in its structure with H2O to form active substances with the strong electrophilic properties and then react with any nucleophilic molecules, primarily leading to genomic DNA damage and subsequent cell death. In this process, those target genes driven by the consensus electrophilic and/or antioxidant response elements (EpREs/AREs) in their promoter regions are also activated or repressed by CDDP. Thereby, we here examined the expression profiling of such genes regulated by two principal antioxidant transcription factors Nrf1 and Nrf2 (both encoded byNfe2l1andNfe2l2,respectively) in diverse cellular signaling responses to this intervention. The results demonstrated distinct cellular metabolisms, molecular pathways and signaling response mechanisms by which Nrf1 and Nrf2 as the drug targets differentially contribute to the anticancer efficacy of CDDP on hepatoma cells and xenograft tumor mice. Interestingly, the role of Nrf1, rather than Nrf2, is required for the anticancer effect of CDDP, to suppress malignant behavior of HepG2 cells by differentially monitoring multi-hierarchical signaling to gene regulatory networks. To our surprise, it was found there exists a closer relationship of Nrf1α than Nrf2 with DNA repair, but the hyperactive Nrf2 inNrf1α−/−cells manifests a strong correlation with its resistance to CDDP, albeit their mechanistic details remain elusive.
Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains
Authors: Mancinelli Chiara , Marx Dagan C. , Gonzalez-Hernandez Alberto J. , Huynh Kevin , Mancinelli Lucia , Arefin Anisul , Khelashvilli George , Levitz Joshua , Eliezer David
Published: August 2023

G protein-coupled receptors (GPCRs) control intracellular signaling cascades via agonist-dependent coupling to intracellular transducers including heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. In addition to their critical interactions with the transmembrane core of active GPCRs, all three classes of transducers have also been reported to interact with receptor C-terminal domains (CTDs). An underexplored aspect of GPCR CTDs is their possible role as lipid sensors given their proximity to the membrane. CTD-membrane interactions have the potential to control the accessibility of key regulatory CTD residues to downstream effectors and transducers. Here we report that the CTDs of two closely related family C GPCRs, metabotropic glutamate receptor 2 (mGluR2) and mGluR3, bind to membranes and that this interaction can regulate receptor function. We first characterize CTD structure with NMR spectroscopy, revealing lipid composition-dependent modes of membrane binding. Using molecular dynamics simulations and structure-guided mutagenesis, we then identify key conserved residues and cancer-associated mutations that modulate CTD-membrane binding. Finally, we provide evidence that mGluR3 transducer coupling is controlled by CTD-membrane interactions in live cells, which may be subject to regulation by CTD phosphorylation and changes in membrane composition. This work reveals a novel mechanism of GPCR modulation, suggesting that CTD-membrane binding may be a general regulatory mode throughout the broad GPCR superfamily.

Significance Statement

G protein-coupled receptors (GPCRs) allow cells to sense and respond to their environment and constitute the largest class of targets for approved therapeutic drugs. Temporally precise GPCR signaling is achieved by coupling the binding of extracellular ligands to the binding of intracellular signal transducers (e.g. heterotrimeric G proteins) and regulators (e.g. β-arrestins). The C-terminal domains (CTDs) of GPCRs are targets of various post-translational modifications and play a critical role in transducer and regulator recruitment. Here we report novel interactions of the CTDs of two GPCRs of the metabotropic glutamate receptor family with cellular membranes. These interactions serve to regulate CTD accessibility and thus, mGluR coupling to transducers and regulators. We propose that dynamic CTD-membrane interaction constitutes a general mechanism for regulating GPCR function.
Situating the parietal memory network in the context of multiple parallel distributed networks using high-resolution functional connectivity
Authors: Kwon Y. , Salvo J.J. , Anderson N. , Holubecki A.M , Lakshman M. , Yoo K. , Kay K. , Gratton C. , Braga R.M.
Published: August 2023

A principle of brain organization is that networks serving higher cognitive functions are widely distributed across the brain. One exception has been the parietal memory network (PMN), which plays a role in recognition memory but is often defined as being restricted to posteromedial association cortex. We hypothesized that high-resolution estimates of the PMN would reveal small regions that had been missed by prior approaches. High-field 7T functional magnetic resonance imaging (fMRI) data from extensively sampled participants was used to define the PMN within individuals. The PMN consistently extended beyond the core posteromedial set to include regions in the inferior parietal lobule; rostral, dorsal, medial, and ventromedial prefrontal cortex; the anterior insula; and ramus marginalis of the cingulate sulcus. The results suggest that, when fine-scale anatomy is considered, the PMN matches the expected distributed architecture of other association networks, reinforcing that parallel distributed networks are an organizing principle of association cortex.
Structure ofC. elegansTMC-2 complex suggests roles of lipid-mediated subunit contacts in mechanosensory transduction
Authors: Clark Sarah , Jeong Hanbin , Posert Rich , Goehring April , Gouaux Eric
Published: August 2023

Mechanotransduction is the process by which a mechanical force, such as touch, is converted into an electrical signal. Transmembrane channel-like (TMC) proteins are an evolutionarily-conserved family of ion channels whose function has been linked to a variety of mechanosensory processes, including hearing and balance sensation in vertebrates and locomotion inDrosophila. The molecular features that tune homologous TMC ion channel complexes to diverse mechanical stimuli are unknown.Caenorhabditis elegansexpress two TMC homologs, TMC-1 and TMC-2, both of which are the likely pore-forming subunits of mechanosensitive ion channels but differ in their expression pattern and functional role in the worm. Here we present the single particle cryo-electron microscopy structure of the native TMC-2 complex isolated fromC. elegans. The complex is composed of two copies each of the pore-forming TMC-2 subunit, the calcium and integrin binding protein CALM-1 and the transmembrane inner ear protein TMIE. Comparison of the TMC-2 complex to the recently published cryo-EM structure of theC. elegansTMC-1 complex reveals differences in subunit composition and highlights conserved protein-lipid interactions, as well as other structural features, that together suggest a mechanism for TMC-mediated mechanosensory transduction.

Significance Statement

One mechanism by which organisms sense their environment is through the perception of mechanical stimuli such as sound, touch, and vibration. Transmembrane channel-like (TMC) proteins are ion channels whose function has been linked to a variety of mechanosensitive processes, including hearing and balance in vertebrates and touch sensation in worms. The molecular mechanisms by which TMCs respond to mechanical stimuli are unknown. Here we present the structure of the TMC-2 complex isolated from worms. Comparison of the TMC-2 complex to the recently solved structure of the worm TMC-1 complex highlights common structural features that are likely important for sensing mechanical stimuli yet also illuminates key differences that may explain the distinct functional roles of TMC-1 and TMC-2 in the worm.
A novel patient-derived cellular platform for validating microglia-targeted therapeutics for Alzheimer’s disease
Authors: Cuní-López Carla , Stewart Romal , Okano Satomi , Redlich Garry L. , Appleby Mark W. , White Anthony R. , Quek Hazel
Published: August 2023

The scarcity of effective biomarkers and therapeutic strategies for predicting disease onset and progression in Alzheimer’s disease (AD) is a major challenge to improve much-needed therapeutic outcomes. Conventional drug discovery approaches have been unsuccessful in providing efficient interventions due to their ‘one-size-fits-all’ nature. As an alternative, personalised drug development holds promise to pre-select responders and identify suitable drug efficacy indicators. In this study, we established a preclinical drug testing strategy by assessing the efficacy of anti-inflammatory drugs in 2D and 3Din vitromodels of monocyte-derived microglia-like cells (MDMi) derived from AD and mild cognitive impairment (MCI) patients, and matched healthy individuals. We observed that the cytokine inflammatory profiles of MDMi in response to drugs clustered separately between cohorts, with the 3D model showing a more defined separation between healthy and patient donors than 2D. By ranking donor and cytokine responses to drugs, we identified that drug efficacy was limited in AD patients and involved cohort-specific responsive cytokines. Our findings suggest that MDMi models have the potential to predict disease progression, stratify responders and identify biomarkers for estimating the efficacy of microglia-targeted drugs. Together, our pipeline could serve as a valuable tool to enhance the clinical translational value of preclinical drug screens and ultimately improve drug outcomes for AD.
Haplotype differences in common bean accessions confer the capacity to flower under Scandinavian summer conditions
Authors: Rendón-Anaya M , Buinovskaja G , Yu L , Ingvarsson PK
Published: August 2023

The capacity to flower under long days has been a major pre-requisite for the adaptation of the common bean to European climates. The complexity of such adaptation has been studied, mostly under the optics of QTL mapping, but still the genetic basis of the trait remains elusive. In the current study we sequenced a collection of >200 accessions ofP. vulgarisof Mesoamerican, Andean and European origin, for which the flowering capacity under long days during the summer season in Sweden was evaluated. Our variant calling strategy allowed us to identify 16.9e6SNPs and 38.6e3long structural variants. Furthermore, we observed gene-pool specific selective sweeps that correspond to the independent domestication events in the Americas. GWAS and haplotype structure tests identified single nucleotide and structural variants strongly associated to the capacity to flower under long days, particularly in chromosome 1.
Acetylcholine Modulates the Precision of Prediction Error in the Auditory Cortex
Authors: Pérez-González David , Lao-Rodríguez Ana B. , Aedo-Sánchez Cristian , Malmierca Manuel S.
Published: August 2023

A fundamental property of sensory systems is their ability to detect novel stimuli in the ambient environment. The auditory brain contains neurons that decrease their response to repetitive sounds but increase their firing rate to novel or deviant stimuli; the difference between both responses is known as stimulus-specific adaptation or neuronal mismatch (nMM). Here, we tested the effect of microiontophoretic applications of ACh on the neuronal responses in the auditory cortex (AC) of anesthetized rats during an auditory oddball paradigm, including cascade controls. Results indicate that ACh modulates the nMM, affecting prediction error responses but not repetition suppression, and this effect is manifested predominantly in infragranular cortical layers. The differential effect of ACh on responses to standards, relative to deviants (in terms of averages and variances), were consistent with the representational sharpening that accompanies an increase in the precision of prediction errors. These findings suggest that ACh plays an important role in modulating prediction error signaling in the AC and gating the access of these signals to higher cognitive levels.
Elasmobranch genome sequencing reveals evolutionary trends of vertebrate karyotype organization
Authors: Yamaguchi Kazuaki , Uno Yoshinobu , Kadota Mitsutaka , Nishimura Osamu , Nozu Ryo , Murakumo Kiyomi , Matsumoto Rui , Sato Keiichi , Kuraku Shigehiro
Published: August 2023

Genomic studies of vertebrate chromosome evolution have long been hindered by the scarcity of chromosome-scale DNA sequences of some key taxa. One of those limiting taxa has been the elasmobranchs (sharks and rays), which harbor species often with numerous chromosomes and enlarged genomes. Here, we report the chromosome-scale genome assembly for the zebra sharkStegostoma tigrinum, an endangered species that has a relatively small genome among sharks (3.71 Gb), as well as for the whale sharkRhincodon typus. Our analysis using a male–female comparison identified an X Chromosome, the first genomically characterized shark sex chromosome. The X Chromosome harbors the Hox C cluster whose intact linkage has not been shown for an elasmobranch fish. The sequenced shark genomes show a gradualism of chromosome length with remarkable length-dependent characteristics—shorter chromosomes tend to have higher GC content, gene density, synonymous substitution rate, and simple tandem repeat content as well as smaller gene length and lower interspersed repeat content. We challenge the traditional binary classification of karyotypes as with and without so-called microchromosomes. Even without microchromosomes, the length-dependent characteristics persist widely in nonmammalian vertebrates. Our investigation of elasmobranch karyotypes underpins their unique characteristics and provides clues for understanding how vertebrate karyotypes accommodate intragenomic heterogeneity to realize a complex readout. It also paves the way to dissecting more genomes with variable sizes to be sequenced at high quality.
Supply chain management practices (SCMPs) and performance nexus in developing and emerging economies (DEEs): a systematic review
Authors: Baisa Goitom Abera , Schäfer Joachim G. , Alemu Abebe Ejigu
Published: August 2023

Purpose

This study aims to synthesize and analyze research on the Supply Chain Management Practices (SCMPs)-performance nexus, examine current knowledge, identify emerging trends, and provide plausible suggestions for future research engagements in the manufacturing sector in the context of Developing and Emerging Economies (DEEs).

Design/methodology/approach

Following a systematic review approach, this study analyzed 20 peer-reviewed scientific journal articles published between 2007 and 2021. The study sample was systematically selected from the Web of Science (WoS) and Google Scholar databases, following strict evaluation and selection criteria.

Findings

Numerous dimensions of SCMPs have been considered in the extant literature; however, six have stood out as the most common. In addition, operational performance stood out as the most widely investigated measure in the SCM literature. Moreover, SCMPs have predominantly shown positive effects on performance outcomes. Methodological issues that future studies should consider are suggested.

Research limitations/implications

The sample size was not sufficiently large relative to the rule of thumb set in the literature because of the scarcity of studies in the manufacturing sector in the DEEs context. Despite these limitations, the results of this study provide crucial insights into knowledge and practice.

Originality/value

This review is the first of its kind to examine the SCMPs-performance nexus in the context of DEEs. Based on the findings of this study, future research directions are proposed.
How is entrepreneurial marketing shaped by E-commerce technology: a case study of Chinese pure-play e-retailers
Authors: Hong Yiwen , Sawang Sukanlaya , Yang Hsiao-Pei (Sophie)
Published: August 2023

Purpose

The focus of this study is on how online-only retailers, known as pure-play e-retailers, leverage e-commerce platforms to identify and pursue market opportunities. Through the perspective of entrepreneurial marketing, this study aims to explore the influence of e-commerce technologies on the decision-making process of entrepreneurial marketing. This exploration is conducted via a case study of pure-play e-retailers based in China.

Design/methodology/approach

This study utilised a qualitative case study methodology to examine the complex processes of entrepreneurial marketing in an online environment. The study gathered detailed insights from both owner-managers and staff members of eight pure-play e-retail businesses. Additionally, the research involved a careful review of the firms' webpages and social media pages. This holistic approach facilitated a comprehensive understanding of their marketing strategies and practices.

Findings

The case study findings indicate that while many core aspects of entrepreneurial marketing remain important, there are distinct factors influencing the entrepreneurial marketing decision-making in the online marketplace. The online EM framework can be visualised as follows: (1) trend-orientated as well as innovative-orientated (2) data-orientated and entrepreneur-orientated (3) innovative-driven customer stimulation (4) orientated towards both platforms and proactiveness.

Originality/value

The paper provides an initial understanding of how digitalisation is enabling and transforming entrepreneurship in companies with high level digitalisation but low level digital development. Building on current entrepreneurial marketing literature, this paper develops an online entrepreneurial marketing framework to enhance understanding of the interaction between e-commerce technology and entrepreneurial marketing decision making.
Investigating the asymmetric effect of income inequality on financial fragility in South Africa and selected emerging markets: a Bayesian approach with hierarchical priors
Authors: Zungu Lindokuhle Talent , Greyling Lorraine
Published: August 2023

Purpose

This study aims to test the validity of the Rajan theory in South Africa and other selected emerging markets (Chile, Peru and Brazil) during the period 1975–2019.

Design/methodology/approach

In this study, the researchers used time-series data to estimate a Bayesian Vector Autoregression (BVAR) model with hierarchical priors. The BVAR technique has the advantage of being able to accommodate a wide cross-section of variables without running out of degrees of freedom. It is also able to deal with dense parameterization by imposing structure on model coefficients via prior information and optimal choice of the degree of formativeness.

Findings

The results for all countries except Peru confirmed the Rajan hypotheses, indicating that inequality contributes to high indebtedness, resulting in financial fragility. However, for Peru, this study finds it contradicts the theory. This study controlled for monetary policy shock and found the results differing country-specific.

Originality/value

The findings suggest that an escalating level of inequality leads to financial fragility, which implies that policymakers ought to be cautious of excessive inequality when endeavouring to contain the risk of financial fragility, by implementing sound structural reform policies that aim to attract investments consistent with job creation, development and growth in these countries. Policymakers should also be cautious when implementing policy tools (redistributive policies, a sound monetary policy), as they seem to increase the risk of excessive credit growth and financial fragility, and they need to treat income inequality as an important factor relevant to macroeconomic aggregates and financial fragility.
IT-related resources, digital marketing capabilities and business performance: moderating effects of digital orientation and technological turbulence
Authors: Ranjan Piyush
Published: August 2023

Purpose

This research intends to develop a conceptual framework investigating how IT-related resources, namely IT advancement (ITAD) and IT alignment (ITAG), utilization relates to digital marketing capabilities (DMCs) development, which in turn improves business performance (BP), as well as how digital orientation (DO) and technological turbulence (TT) moderate these effects.

Design/methodology/approach

This study employs an online email-based survey technique to collect primary cross-sectional data from 388 small and medium-sized enterprises operating in India. Moderated hierarchical regression was used to validate the hypothesized relationships.

Findings

ITAD and ITAG are significant drivers of DMCs, and these capabilities positively influence BP. Moreover, DO strengthens the positive effect of ITAD and ITAG on DMCs, with ITAD having a higher impact than ITAG. Similarly, DMCs have a greater positive effect on BP in an environment with high TT.

Originality/value

Despite increased interest in the information technology resources required for the development of DMCs, less attention has been paid to the relationship between ITAD and ITAG resources and DMCs. In addition, few researchers investigate the moderating influence of DO on the relationship between IT-related resources and DMCs, as well as TT on the association between DMCs and BP.
Research-practice gap in accounting journals? A topic modeling approach
Authors: Federsel Florian Philipp , Fülbier Rolf Uwe , Seitz Jan
Published: August 2023

Purpose

A gap between research and practice is commonly perceived throughout accounting academia. However, empirical evidence on the magnitude of this detachment remains scarce. The authors provide new evidence to the ongoing debate by introducing a novel topic-based approach to capture the research-practice gap and quantify its extent. They also explore regional differences in the research-practice gap.

Design/methodology/approach

The authors apply the unsupervised machine learning approach Latent Dirichlet allocation (LDA) to compare the topical composition of 2,251 articles from six premier research, practice and bridging journals from the USA and Europe between 2009 and 2019. The authors extend the existing methods of summarizing literature and develop metrics that allow researchers to evaluate the research-practice gap. The authors conduct a plethora of additional analyses to corroborate the findings.

Findings

The results substantiate a pronounced topic-related research-practice gap in accounting literature and document its statistical significance. Moreover, the authors uncover that this gap is more pronounced in the USA than in Europe, highlighting the importance of institutional differences between academic communities.

Practical implications

The authors objectify the debate about the extent of a research-practice gap and stimulate further discussions about explanations and consequences.

Originality/value

To the best of the authors' knowledge, this is the first paper to deploy a rigorous machine learning approach to measure a topic-based research-practice gap in the accounting literature. Additionally, the authors provide theoretical rationales for the extent and regional differences in the research-practice gap.
Decision-making in organizations: should managers use AI?
Authors: Brink Anniek , Benyayer Louis-David , Kupp Martin
Published: August 2023

Purpose

Prior research has revealed that a large share of managers is reluctant towards the use of artificial intelligence (AI) in decision-making. This aversion can be caused by several factors, including individual drivers. The purpose of this paper is to better understand the extent to which individual factors influence managers’ attitudes towards the use of AI and, based on these findings, to propose solutions for increasing AI adoption.

Design/methodology/approach

The paper builds on prior research, especially on the factors driving the adoption of AI in companies. In addition, data was collected by means of 16 expert interviews using a semi-structured interview guideline.

Findings

The study concludes on four groups of individual factors ranked according to their importance: demographics, familiarity, psychology and personality. Moreover, the findings emphasized the importance of communication and training, explainability and transparency and participation in the process to foster the adoption of AI in decision-making.

Research limitations/implications

The paper identifies four ways to foster AI integration for organizational decision-making as areas for further empirical analysis by business researchers.

Practical implications

This paper offers four ways to foster AI adoption for organizational decision-making: explaining the benefits and training the more adverse categories, explaining how the algorithms work and being transparent about the shortcomings, striking a good balance between automated and human-made decisions, and involving users in the design process.

Social implications

The study concludes on four groups of individual factors ranked according to their importance: demographics, familiarity, psychology and personality. Moreover, the findings emphasized the importance of communication and training, explainability and transparency and participation in the process to foster the adoption of AI in decision-making.

Originality/value

This study is one of few to conduct qualitative research into the individual factors driving usage intention among managers; hence, providing more in-depth insights about managers’ attitudes towards algorithmic decision-making. This research could serve as guidance for developers developing algorithms and for managers implementing and using algorithms in organizational decision-making.
Risk attitudes impact the entrepreneurial choices of Chinese agricultural laborers: a deep mechanism analysis
Authors: Wu Guanghao , Shi Xiuyi , Li Jiajia
Published: August 2023

Purpose

The purpose of this paper is to precisely measure the risk attitudes of Chinese agricultural laborers and then analyze the impact and mechanism of risk attitudes on the entrepreneurial choices of Chinese agricultural laborers.

Design/methodology/approach

This paper is based on the theory of expected utility function and utilizes the authoritative China Family Panel Studies (CFPS) to accurately measure the risk attitudes of 7,639 Chinese agricultural laborers through experimental methods. In the empirical analysis, this paper employed Probit, IV-Probit and mediation effect models to examine the research hypotheses.

Findings

First, agricultural laborers with the lowest risk appetite account for 54.8%, which is 8.69 times the number of agricultural laborers with the highest risk appetite. Second, agricultural laborers preferring risk are more likely to engage in entrepreneurship; this result has been validated through a series of robustness tests. Third, mechanism analysis shows that risk attitude drives the entrepreneurship of Chinese agricultural laborers through improving interpersonal trust, social interaction and formal credit behavior.

Originality/value

Existing research has mainly investigated the impact of risk attitudes on the entrepreneurial choices of the general population, with limited attention paid to agricultural laborers. The potential mechanisms in that process remain unclear, and the measurement results of risk attitude also require further precision. Based on experimental method, this paper not only helps clarify the relationship between risk attitudes and agricultural laborers entrepreneurship in China, but also provides policy recommendations to promote agricultural laborers entrepreneurship and drive rural development.
Pre‐operative gastric ultrasound in patients at risk of pulmonary aspiration: a prospective observational cohort study
Authors: Baettig S. J. , Filipovic M. G. , Hebeisen M. , Meierhans R. , Ganter M. T.
Published: August 2023

Point‐of‐care gastric sonography offers an objective approach to assessing individual pulmonary aspiration risk before induction of general anaesthesia. We aimed to evaluate the potential impact of routine pre‐operative gastric ultrasound on peri‐operative management in a cohort of adult patients undergoing elective or emergency surgery at a single centre. According to pre‐operative gastric ultrasound results, patients were classified as low risk (empty, gastric fluid volume ≤ 1.5 ml.kg‐1 body weight) or high risk (solid, mixed or gastric fluid volume > 1.5 ml.kg‐1 body weight) of aspiration. After sonography, examiners were asked to indicate changes in aspiration risk management (none; more conservative; more liberal) to their pre‐defined anaesthetic plan and to adapt it if patient safety was at risk. We included 2003 patients, 1246 (62%) of which underwent elective and 757 (38%) emergency surgery. Among patients who underwent elective surgery, 1046/1246 (84%) had a low‐risk and 178/1246 (14%) a high‐risk stomach, with this being 587/757 (78%) vs. 158/757 (21%) among patients undergoing emergency surgery, respectively. Routine pre‐operative gastric sonography enabled changes in anaesthetic management in 379/2003 (19%) of patients, with these being a more liberal approach in 303/2003 (15%). In patients undergoing elective surgery, pre‐operative gastric sonography would have allowed a more liberal approach in 170/1246 (14%) and made a more conservative approach indicated in 52/1246 (4%), whereas in patients undergoing emergency surgery, 133/757 (18%) would have been managed more liberally and 24/757 (3%) more conservatively. We showed that pre‐operative gastric ultrasound helps to identify high‐ and low‐risk situations in patients at risk of aspiration and adds useful information to peri‐operative management. Our data suggest that routine use of pre‐operative gastric ultrasound may improve individualised care and potentially impact patient safety.