bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and dynamic changes in P-Rex1 upon activation by PIP3and inhibition by IP4
Authors: Ravala Sandeep K. , Adame-Garcia Sendi Rafael , Li Sheng , Chen Chun-Liang , Cianfrocco Michael A. , Gutkind J. Silvio , Cash Jennifer N. , Tesmer John J. G.
Published: September 2023

PIP3-dependent Rac exchanger 1 (P-Rex1) is abundantly expressed in neutrophils and plays central roles in chemotaxis and cancer metastasis by serving as a guanine-nucleotide exchange factor (GEF) for Rac. The enzyme is synergistically activated by PIP3and the heterotrimeric Gβγ subunits, but mechanistic details remain poorly understood. While investigating the regulation of P-Rex1 by PIP3, we discovered that Ins(1,3,4,5)P4(IP4) inhibits P-Rex1 activity and induces large decreases in backbone dynamics in diverse regions of the protein. Cryo-electron microscopy analysis of the P-Rex1·IP4complex revealed a conformation wherein the pleckstrin homology (PH) domain occludes the active site of the Dbl homology (DH) domain. This configuration is stabilized by interactions between the first DEP domain (DEP1) and the DH domain and between the PH domain and a 4-helix bundle (4HB) subdomain that extends from the C-terminal domain of P-Rex1. Disruption of the DH–DEP1 interface in a DH/PH-DEP1 fragment enhanced activity and led to a more extended conformation in solution, whereas mutations that constrain the occluded conformation led to decreased GEF activity. Variants of full-length P-Rex1 in which the DH–DEP1 and PH–4HB interfaces were disturbed exhibited enhanced activity during chemokine-induced cell migration, confirming that the observed structure represents the autoinhibited state in living cells. Interactions with PIP3-containing liposomes led to disruption of these interfaces and increased dynamics protein-wide. Our results further suggest that inositol phosphates such as IP4help to inhibit basal P-Rex1 activity in neutrophils, similar to their inhibitory effects on phosphatidylinositol-3-kinase.
Mechanisms of action and synergies of a novel lipid IVAbiosynthesis inhibitor
Authors: Holden Emma R , Yasir Muhammad , Turner A Keith , Webber Mark A , Charles Ian , Siegwart Ed , Raynham Tony , Mistry Ajay , George John , Gilmour Matthew
Published: September 2023

The development of novel antimicrobials provides additional treatment options for infectious diseases, including antimicrobial resistant infections. There are many hurdles to antimicrobial development and identifying an antimicrobial’s mechanism of action is a crucial step in progressing candidate molecules through the drug discovery pipeline. We used the genome wide screening method TraDIS-Xpressto identify genes in two model Gram-negative bacteria that affected sensitivity to three analogues of a novel antimicrobial compound (OPT-2U1). TraDIS-Xpressidentified that all three analogues targeted the lipid IVAbiosynthetic pathway inE. coliandSalmonellaTyphimurium. Specifically, we determined that the antimicrobial target was likely to be LpxD, and validated this by finding a 5 log2-fold increase in the MIC of the OPT-2U1 analogues inE. coliwhenlpxDwas overexpressed. Synergies were identified between OPT-2U1 analogues combined with rifampicin or colistin, to varying strengths, in bothE. coliandS. Typhimurium. LPS composition was a likely reason for differences betweenE. coliand S.Typhimurium, as perturbation of LPS synthesis affected synergy between antibiotics and OPT-2U1 analogues. Finally, genes involved in ATP synthesis and membrane signalling functions were also found to affect the synergy between colistin and OPT-2U1 analogues. TraDIS-Xpresshas proven a powerful tool to rapidly assay all genes (and notably, essential genes) within a bacterium for roles in dictating antimicrobial sensitivity. This study has confirmed the predicted target pathway of OPT-2U1 and identified synergies which could be investigated for development of novel antimicrobial formulations.

Data Summary

Nucleotide sequence data supporting the analysis in this study has been deposited in ArrayExpress under the accession number E-MTAB-13250. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.
Sparse clustered inhibition projects sequential activity onto unique neural subspaces
Authors: Lehr Andrew B , Kumar Arvind , Tetzlaff Christian
Published: September 2023

Neural activity in the brain traces sequential trajectories on low dimensional subspaces. For flexible behavior, these neural subspaces must be manipulated and reoriented within tens of milliseconds. Using mathematical analysis and simulation of a recurrently connected neural circuit for sequence generation, we report that incorporating a subtype of interneurons that provides sparse but clustered inhibition enables the projection of sequential activity onto task- or context-specific neural subspaces. Depending on the sparsity of inhibitory projections, neural subspaces could be arbitrarily rotated with respect to the intrinsic subspace, without altering the key aspects of sequence generation. Thus, we propose a circuit motif and mechanism by which inhibitory interneurons can enable flexible switching between neural subspaces on a fast timescale of milliseconds, controlled by top down signals.
Single-molecule FRET and tracking of transfected biomolecules: multi-dimensional protein dynamics in living cells
Authors: Anandamurugan Abhinaya , Eidloth Antonia , Wortmann Philipp , Schrangl Lukas , Aprile-Garcia Fernando , Lan Chenyang , Sawarkar Ritwick , Schütz Gerhard J. , Hugel Thorsten
Published: September 2023

Proteins in cells exhibit conformational dynamics, equally influenced by dynamic interactions with other biomolecules and their spatial variations, which can be induced by the protein’s compartment. Altogether this multi-dimensional dynamic is difficult to measurein cellula, because of limitations in instrumentation, fluorescence methodologies and the difficulty to track freely diffusing molecules. Here, we present a bottom-up engineering approach, which allows us to track transfected proteinsin cellulaand analyze time-resolved single-molecule FRET efficiencies. This has been achieved by alternating laser excitation (ALEX) based three-channel (donor, acceptor and FRET intensity) tracking with a live-cell HILO microscope. Unexpectedly, we find that the heat shock protein Hsp90 shows different conformational populationsin vitroandin cellula. Moreover, Hsp90’s conformational states depend on the localization within the cell, which is demonstrated by comparing a physical (microinjection) and a biological (SLO) transfection method. FRET-TTB (Tracking of Transfected Biomolecules) opens the path to study protein conformational dynamics of transfected and native biomoleculesin cellula, including time-resolved cellular localization.
Kinematic performance declines as group size increases during escape responses in a schooling coral reef fish
Authors: Bacchus Monica D. , Domenici Paolo , Killen Shaun S. , McCormick Mark I. , Nadler Lauren E.
Published: September 2023

Escaping predation is essential for species survival, but prey must effectively match their response to the perceived threat imposed by a predator. For social animals, one mechanism to reduce risk of predation is living in larger group sizes, which dilutes each individual’s risk of capture. When a predator attacks, individuals from a range of taxa (e.g., fishes, sharks, amphibians) perform an escape response, to evade the attack. Here, using the schooling coral reef damselfishChromis viridis, we assess if there is an optimal group size that maximizes both individual escape response performance as well as group cohesion and coordination following a simulated predator attack, comparing schools composed of four, eight, and sixteen fish. We found that fish in various group sizes exhibited no difference in their reaction timing to a simulated predator attack (i.e., escape latency), but larger groups exhibited slower kinematics (i.e., lower average turning rate and shorter distance covered during the escape response), potentially because larger groups perceived the predator attack as less risky due to safety in numbers. Both school cohesion and coordination (as measured through alignment and nearest neighbor distance, respectively) declined in the 100ms after the predator’s attack. While there was no impact of group size on alignment, larger group sizes exhibited closer nearest neighbor distances at all times. This study highlights that larger group sizes may allow individuals to save energy on costly behavioral responses to avoid predators, potentially through a greater threshold of the threat necessary to trigger a rapid escape response.
Characterization of Dr20/22: Molecular Insights and Antibody Response in Naturally Infected Dogs withDirofilaria repens
Authors: Pękacz Mateusz , Basałaj Katarzyna , Młocicki Daniel , Kamaszewski Maciej , Carretón Elena , Morchón Rodrigo , Wiśniewski Marcin , Zawistowska-Deniziak Anna
Published: September 2023

Subcutaneous dirofilariasis, caused by the parasitic nematode Dirofilaria repens, is a growing concern in Europe, affecting both dogs and humans. This study focused on D. repens Dr20/22, a protein encoded by an alt (abundant larval transcript) gene family. While well-documented in L3 larvae of other filariae species, this gene family had not been explored in dirofilariasis. The research involved cloning Dr20/22 cDNA, molecular characterization, and evaluating its potential application in the diagnosis of dirofilariasis. Although Real-Time analysis revealed mRNA expression in both adult worms and microfilariae, the native protein remained undetected in lysates from both developmental stages. This suggests the protein’s specificity for L3 larvae and may be related to a process called SLTS (spliced leader trans-splicing), contributing to stage-specific gene expression. The antigen’s apparent specificity for invasive larvae makes it a strong candidate for an early dirofilariasis marker. ELISA tests using sera from infected and healthy dogs detected specific IgG antibody responses in both groups, indicating that specific IgG in healthy dog sera may contribute to dirofilariasis immunity. Although further research is necessary, the molecular and immunological characterization of Dr20/22 can enhance our understanding of host-parasite interactions and provide insights into the mechanisms that facilitate immune system evasion.
LeishmaniaRibosomal Protein (RP) paralogous genes compensate each other’s expression maintaining protein native levels
Authors: Borges Francisca S. , Quilles José C. , Lorenzon Lucas B. , Espada Caroline R. , Freitas-Castro Felipe , Defina Tânia P. A. , Holetz Fabíola B. , Cruz Angela K.
Published: September 2023

In the protozoan parasite Leishmania, most of the genes encoding for ribosomal proteins (RPs) are present as two or more copies in the genome, their untranslated regions (UTRs) are predominantly divergent, and might be associated with a distinct regulation of the paralogous genes’ expression. Here, we investigated the expression profiles of two RPs (S16 and L13a) encoded by duplicated genes in Leishmania major. The genes encoding for S16 protein have identical CDSs and divergent UTRs while the L13a CDSs diverge in two amino acids with divergent UTRs. Using CRISPR/Cas9 genomic editing system, we generated knockout (Δ) and tagged transfectants for each paralog of L13a and S16. Combining tagged and Δ cell lines we show that the expression of both RPS16 and RPL13a isoforms differ throughout the parasite development with one of the isoforms being always more abundant than its respective copy. Additionally, compensatory expression was observed for each paralog when one of the isoforms was deleted, evidencing functional conservation of these proteins. Such phenomenon is related to post-translational processes, since the compensation happened at the protein levels, with no alterations observed at the transcript levels. Ribosomal profiles for RPL13a point out a standard behavior for these paralogues as already reported for other RPs in trypanosomatids, showing its interaction with heavy RNA-protein complexes. The identification of sets of proteins binding specifically to the 3’UTRs of either the high or less abundant transcripts suggests a possible role of these proteins to differently control the levels of expression of these RP genes. In addition, conserved cis-elements were identified in the 3’UTRs of RPS16 or RPL13a; among these, exclusive cis-elements for the more or for the less expressed transcripts were identified.
An enduring role for hippocampal pattern completion in addition to an emergent non-hippocampal contribution to holistic episodic retrieval after a 24-hour delay
Authors: Joensen Bárður H. , Ashton Jennifer E. , Berens Sam C. , Gaskell M. Gareth , Horner Aidan J.
Published: September 2023

Episodic memory retrieval is associated with the holistic neocortical reinstatement of all event information; an effect driven by hippocampal pattern completion. However, whether holistic reinstatement occurs, and whether hippocampal pattern completion continues to drive reinstatement, after a period of consolidation is unclear. Theories of systems consolidation predict either a time-variant or -invariant role of the hippocampus in the holistic retrieval of episodic events. Here, we assessed whether episodic events continue to be reinstated holistically and whether hippocampal pattern completion continues to facilitate holistic reinstatement following a period of consolidation. Female and male human participants learnt ‘events’ that were composed of multiple overlapping pairs of event elements (e.g., person-location, object-location, location-person). Importantly, encoding occurred either immediately before or 24-hours before retrieval. Using fMRI during the retrieval of events, we show evidence for holistic reinstatement, as well as a correlation between reinstatement and hippocampal pattern completion, regardless of whether retrieval occurred immediately or 24-hours after encoding. Thus, hippocampal pattern completion continues to contribute to holistic reinstatement after a delay. However, our results also revealed that some holistic reinstatement can occur without evidence for a corresponding signature of hippocampal pattern completion after a delay (but not immediately after encoding). We therefore show that hippocampal pattern completion, in addition to a non-hippocampal process, has a role in holistic reinstatement following a period of consolidation. Our results point to a consolidation process where the hippocampus and neocortex may work in an additive, rather than compensatory, manner to support episodic memory retrieval.
Multiple evolutionary pathways lead to vancomycin resistance inClostridioides difficile
Authors: Buddle Jessica E. , Wright Rosanna C. T. , Turner Claire E. , Chaudhuri Roy R. , Brockhurst Michael A. , Fagan Robert P.
Published: September 2023

Clostridioides difficileis an important human pathogen, for which there are very limited treatment options, primarily the glycopeptide antibiotic vancomycin. In recent years vancomycin resistance has emerged as a serious problem in several Gram positive pathogens, but high level resistance has yet to be reported forC. difficile, although it is not known if this is due to constraints upon resistance evolution in this species. Here we show that resistance to vancomycin can evolve rapidly under ramping selection but is accompanied by severe fitness costs and pleiotropic trade-offs, including sporulation defects that would be expected to severely impact transmission. We identified two distinct pathways to resistance, both of which are predicted to result in changes to the muropeptide terminal D-Ala-D-Ala that is the primary target of vancomycin. One of these pathways involves a previously uncharacterised D,D-carboxypeptidase, expression of which is controlled by a dedicated two-component signal transduction system. Our findings suggest that whileC. difficileis capable of evolving high-level vancomycin resistance, this outcome may be limited clinically due to pleiotropic effects on key pathogenicity trains. Moreover, our data provide a mutational roadmap to inform genomic surveillance.
Structural and mechanistic insights into human choline and ethanolamine transport
Authors: Ri Keiken , Weng Tsai-Hsuan , Claveras Cabezudo Ainara , Jösting Wiebke , Yu Zhang , Bazzone Andre , Leong Nancy C.P. , Welsch Sonja , Doty Raymond T. , Gursu Gonca , Lim Tiffany Jia Ying , Schmidt Sarah Luise , Abkowitz Janis L. , Hummer Gerhard , Wu Di , Nguyen Long N , Safarian Schara
Published: September 2023

Human feline leukemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and 2) are members of the major facilitator superfamily1. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN, and Fowler syndrome2–7. Earlier studies concluded that FLVCR1 may function as a putative heme exporter8–12, while FLVCR2 was suggested to act as a heme importer13, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters14–17. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across human plasma membranes, utilizing a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unraveled the coordination chemistry underlying their substrate interactions. Within the binding pocket of both transporters, we identify fully conserved tryptophan and tyrosine residues holding a central role in the formation of cation-π interactions, essential for choline and ethanolamine selectivity. Our findings not only clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhancing our comprehension of disease-associated mutations that interfere with these vital processes, but also shed light on the conformational dynamics of these MFS-type proteins during the transport cycle.
Cerebellar circuits for disinhibition and synchronous inhibition
Authors: Lackey Elizabeth P. , Moreira Luis , Norton Aliya , Hemelt Marie E. , Osorno Tomas , Nguyen Tri M. , Macosko Evan Z. , Lee Wei-Chung Allen , Hull Court A. , Regehr Wade G.
Published: September 2023

The cerebellar cortex contributes to diverse behaviors by transforming mossy fiber inputs into predictions in the form of Purkinje cell (PC) outputs, and then refining those predictions1. Molecular layer interneurons (MLIs) account for approximately 80% of the inhibitory interneurons in the cerebellar cortex2, and are vital to cerebellar processing1,3. MLIs are thought to primarily inhibit PCs and suppress the plasticity of excitatory synapses onto PCs. MLIs also inhibit, and are electrically coupled to, other MLIs4–7, but the functional significance of these connections is not known1,3. Behavioral studies suggest that cerebellar-dependent learning is gated by disinhibition of PCs, but the source of such disinhibition has not been identified8. Here we find that two recently recognized MLI subtypes2, MLI1 and MLI2, have highly specialized connectivity that allows them to serve very different functional roles. MLI1s primarily inhibit PCs, are electrically coupled to each other, fire synchronously with other MLI1s on the millisecond time scalein vivo, and synchronously pause PC firing. MLI2s are not electrically coupled, they primarily inhibit MLI1s and disinhibit PCs, and are well suited to gating cerebellar-dependent learning8. These findings require a major reevaluation of processing within the cerebellum in which disinhibition, a powerful circuit motif present in the cerebral cortex and elsewhere9–17, greatly increases the computational power and flexibility of the cerebellum. They also suggest that millisecond time scale synchronous firing of electrically-coupled MLI1s helps regulate the output of the cerebellar cortex by synchronously pausing PC firing, which has been shown to evoke precisely-timed firing in PC targets18.
Microvascular Specificity of Spin Echo BOLD fMRI: Impact of EPI Echo Train Length
Authors: van Horen T.W.P. , Siero J.C.W. , Bhogal A.A. , Petridou N. , Báez-Yáñez M.G.
Published: September 2023

A spatially specific fMRI acquisition requires specificity to the microvasculature that serves active neuronal sites. Macrovascular contributions will reduce the microvascular specificity but can be reduced by using spin echo (SE) sequences that use a π pulse to refocus static field inhomogeneities near large veins. The microvascular specificity of a SE-echo planar imaging (SE-EPI) scan depends on the echo train length (ETL)-duration, but the dependence is not well-characterized in humans at 7T. To determine how microvascular-specific SE-EPI BOLD is in humans at 7T, we developed a Monte Carlo voxel model that computes the signal of a proton ensemble residing in a vasculature subjected to a SE-EPI pulse sequence. We characterized the ETL-duration dependence of the microvascular specificity by simulating the BOLD signal as a function of ETL, the range adhering to experimentally realistic readouts. We performed a validation experiment for our simulation observations, in which we acquired a set of SE-EPI BOLD time series with varying ETL during a hyperoxic gas challenge. Both our simulations and measurements show an increase in macrovascular contamination as a function of ETL, with an increase of 30% according to our simulation and 60% according to our validation experiment between the shortest and longest ETL durations (23.1 - 49.7 ms). We conclude that the microvascular specificity decreases heavily with increasing ETL-durations. We recommend reducing the ETL-duration as much as possible to minimize macrovascular contamination in SE-EPI BOLD experiments. We additionally recommend scanning at high resolutions to minimize partial volume effects with CSF. CSF voxels show a large BOLD response, which can be attributed to both the presence of large veins (high blood volume) and molecular oxygen-inducedT1-shortening (significant in a hyperoxia experiment). The magnified BOLD signal in a GM-CSF partial volume voxel reduces the desired microvascular specificity and, therefore, will hinder the interpretation of functional MRI activation patterns.
Differential Survival In Carrion Crows Through Eavesdropping on Human Speech: An Agent-Based Model
Authors: Schalz Sabrina
Published: September 2023

Wild carrion crows eavesdrop on human speech and respond more strongly to it than to the calls of pigeons or parakeets. However, it remains unclear whether this behaviour provides any benefit to them, and if so, under which environmental conditions such a benefit could be expected. I used an agent-based model to examine the effect of eavesdropping on the survival of a carrion crow under different environmental conditions. The crow could gain points from foraging, but also had to avoid encounters with a human in order to not lose points. In addition to eavesdropping, it could visually scan the patch for human presence and, once detected, could keep track of the human’s location. I found that eavesdropping led to higher final scores and higher rates of survival than visual scanning alone if the human density on the patch was elevated, or if there were visual obstacles reducing the accuracy of visual scans. Such environmental conditions are particularly common for urban crows foraging in areas such as public parks. The model provides a proof of concept for future empirical research into the potentially differential survival of urban crows eavesdropping on speech.
Synergistic olfactory processing for social plasticity in desert locusts
Authors: Petelski Inga , Günzel Yannick , Sayin Sercan , Kraus Susanne , Couzin-Fuchs Einat
Published: September 2023

1

Desert locust plagues threaten the food security of millions. Central to their formation is crowding-induced social plasticity from ‘solitarious’ to ‘gregarious‘ phenotypes. We investigated the impact of population density changes on locusts’ foraging choices and their neurobiology by examining how relevant food and social odors are coded in the antennal lobe. Our analysis shows that gregarious locusts are highly attentive to social cues during foraging, with olfaction playing an essential role. Using calcium imaging, we show that corresponding odors are encoded by projection neurons, revealing a stable combinatorial response map. Transient dynamics in the glomeruli converge into temporally evolving response motifs in the somata that differ between gregarious and solitarious insects. The dynamics of response motifs facilitate a crowding-dependent synergy between olfactory processing of food-related and social odors. Our study demonstrates the effectiveness of calcium imaging for locust olfaction, suggesting a crowding-induced adaptation to enhance food detection in swarms.

2

Teaser

In dense swarms, desert locusts optimize foraging efficiency by exhibiting an enhanced olfactory response to food odors.
Mate choice in the brain: Species differ in how male traits ‘turn on’ gene expression in female brains
Authors: Keagy Jason , Hofmann Hans A. , Boughman Janette W.
Published: September 2023

Mate choice plays a fundamental role in speciation, yet we know little about the molecular mechanisms that underpin this crucial decision-making process. Female stickleback fish differentially adapted to limnetic and benthic habitats and considered members of reproductively isolated species use different male traits to evaluate prospective partners and reject heterospecific males. Here, we integrate behavioral data from a mate choice experiment involving benthic and limnetic fish with gene expression data from the brains of females making these mate choice decisions. We find substantial gene expression variation between limnetic and benthic species, regardless of behavioral context, suggesting general divergence in gene expression patterns in female brains, in accordance with their genetic differentiation. Intriguingly, female gene co-expression modules covary with male display traits but in opposing directions for sympatric populations of the two species, suggesting male displays elicit a genomic response that reflects known differences in female preferences which serve to isolate the species. Furthermore, our analysis confirms the role of numerous candidate genes previously implicated in female mate choice decision-making in other teleost species, suggesting that these cognitive molecular processes are, in part, evolutionarily conserved. Taken together, our study adds important new insights to our understanding of the molecular processes underlying female decision-making that maintain isolation between diverging species.
DNA-dependent phase separation by human SSB2 (NABP1/OBFC2A) protein points to adaptations to eukaryotic genome repair processes
Authors: Kovács Zoltán J. , Harami Gábor M. , Pálinkás János , Kuljanishvili Natalie , Hegedüs József , Harami-Papp Hajnalka , Mahmudova Lamiya , Khamisi Lana , Szakács Gergely , Kovács Mihály
Published: September 2023

Single-stranded DNA binding proteins (SSBs) are ubiquitous across all domains of life and play essential rolesviastabilizing and protecting single-stranded (ss) DNA as well as organizing multiprotein complexes during DNA replication, recombination, and repair. Two mammalian SSB paralogs (hSSB1 and hSSB2 in humans) were recently identified and shown to be involved in various genome maintenance processes. Following our recent discovery of the liquid-liquid phase separation (LLPS) propensity ofE. coli(Ec) SSB, here we show that hSSB2 also forms LLPS condensates under physiologically relevant ionic conditions. Similar to that seen for EcSSB, we demonstrate the essential contribution of hSSB2’s C-terminal intrinsically disordered region (IDR) to condensate formation, and the selective enrichment of various genome metabolic proteins in hSSB2 condensates. However, in contrast to EcSSB-driven LLPS that is inhibited by ssDNA binding, hSSB2 phase separation requires single-stranded nucleic acid binding, and is especially facilitated by ssDNA. Our results reveal an evolutionarily conserved role for SSB-mediated LLPS in the spatiotemporal organization of genome maintenance complexes. At the same time, differential LLPS features of EcSSB and hSSB2 point to functional adaptations to prokaryoticversuseukaryotic genome metabolic contexts.
The Hsp60 C-terminus Senses Substrate and Triggers Allosteric ATP Hydrolysis
Authors: Von Salzen Daniel , Rodriguez Alejandro , Ullah Anwar , Bernal Ricardo Andres
Published: September 2023

The human mitochondrial chaperonin Hsp60/Hsp10 plays an essential role in maintaining protein homeostasis through an ATP dependent protein refolding mechanism. In the absence of this chaperonin, all cells perish due to an accumulation of misfolded aggregates. Despite its importance, the detailed mechanism of ATP hydrolysis and the role of the C-terminal tail remains unresolved. Here we show that the C-terminal tail acts as a sensor for the arrival of substrate into the chaperonin internal chamber that directly leads to an allosteric trigger of ATP hydrolysis in a neighboring subunit. Our results reveal that removal of the C-terminal tail leads to normal binding of both ATP and a misfolded substrate, but the chaperonin stalls and is unable to progress along the protein folding reaction cycle because it has lost the ability to sense the presence of substrate. High resolution reconstructions reveal the detailed mechanism of ATP hydrolysis where access to the γ-phosphate is blocked by the carboxylate oxygen of an aspartate residue. Binding of the C-terminal tail to substrate displaces this oxygen and allows ATP hydrolysis. These results bring a better understanding of how Hsp60 functions at an atomic level where substrate arrival activates ATP hydrolysis through an allosteric trigger.
Beginning farmer status and financial performance differentials
Authors: Weir Rebecca , Hadrich Joleen , Bonanno Alessandro , Jablonski Becca B.R.
Published: September 2023

Purpose

Beginning Farmer and Rancher programs are available for operators with ten years of experience or less on any farm. These programs support farmers who are starting operations, often without an initial asset allocation. However, some beginning farmers acquire operations that are already established, with substantial assets in place. The authors investigate whether a profitability gap exists between beginning farmers entering the industry ex novo and those operating a preexisting operation and if so, what factors contribute to the gap.

Design/methodology/approach

The authors utilize the Blinder-Oaxaca decomposition to determine what drives financial differences between first-generation beginning farmers, second-generation beginning farmers and established farmers using a unique farm-level panel dataset from 1997 to 2021.

Findings

Results indicate that first- and second-generation beginning farmers have similar operating profit margins, but first-generation beginning farmers have a statistically higher rate of return on assets than second-generation beginning farmers. Established farmers outperform second-generation beginning farmers on both the operating profit margin and rate of return on assets. These results suggest that economic viability for beginning farmers differs depending upon the initial status of their operation, suggesting that heterogenous policies may be more impactful in supporting various pathways to enter agriculture.

Originality/value

This analysis is the first to identify beginning farmers that enter the industry without an asset base and those that take over a principal operator role on an established farm through an assumed farm transition. The authors quantify differences in financial performance using detailed accrual-based financial data that tracks farms over time in one dataset.
Practical implications of workplace ostracism: a systematic literature review
Authors: Mohammad Sheikh Sajid , Nazir Nazir A.
Published: September 2023

Purpose

This review analyzes data from research articles published from 2010 to 2022 related to workplace ostracism which include theoretical or empirical practical implications. The primary motive of this review is to identify main themes of practical implications relevant to workplace ostracism.

Design/methodology/approach

In total, 86 research articles published in 56 journals were retrieved from six well-known management science databases, namely, Science Direct, Emerald Online, Springer Link, Taylor and Francis, Wiley and Sage. The affinity diagram was utilized to organize the practical implications of the studies into meaningful themes. Moreover, in order to prioritize the main themes, the Pareto diagram was utilized.

Findings

Eleven themes have been used to categorize the practical implications of the reviewed articles, demonstrating various human resource (HR) interventions for avoiding or limiting the feelings of ostracism at work. Specifically, they focus on training and development, culture, formal and informal meetings, interpersonal relationships, task interdependence, monitoring, trust and transparency, proper channel, job autonomy and individual characteristics.

Originality/value

While many systematic and traditional literature reviews have been undertaken in an attempt to thoroughly organize extant literature on various aspects of workplace ostracism, no study has addressed the main themes of practical implications vis-à-vis employees experiencing workplace ostracism. Moreover, the majority of them are apparently out of date (prior to 2019), and there is just one study undertaken up to 2020.
Public relations professionals' views of moral entrepreneurship: an exploration of the concept, its benefits and barriers
Authors: Erzikova Elina , Martinelli Diana
Published: September 2023

Purpose

The purpose of this paper is to examine US public relations professionals' perceptions of the benefits and challenges associated with the concept of moral entrepreneurship, defined as the purposeful process of changing or creating new institutionalized ethical norms. This study argues that the concept of moral entrepreneurship provides organizations with a potentially valuable framework to actively recognize societal pressures and problems and act accordingly to better the environment in which the organization resides and operates.

Design/methodology/approach

This exploratory study uses purposive in-depth interviews with 25 diverse public relations professionals, who represented communication firms, in-house public relations departments, higher education, nonprofits and government.

Findings

Respondents assigned a high value to the concept of moral entrepreneurship: In addition to its being viewed as the right thing to do, they recognized its practice as a way to help organizations recruit and retain employee talent and improve stakeholder trust. However, based on the interviews, organizational leadership is the primary initiator of ethical changes; therefore, without a seat at the management table, practitioners lack the influence to initiate such new organizational directions and take on the role of moral entrepreneurs only when directed to do so by their superiors. Barriers to adopting a moral entrepreneurship approach included a limited budget and shortage of staff, employees' resistance to change, fear of failure, poor leadership and a politically polarized workplace.

Practical implications

Practice implications include considerations for furthering moral entrepreneurship in organizations.

Originality/value

This study is the first to explore the applicability of the concept of moral entrepreneurship in public relations. The paper underscores the need for further discussion around novel approaches to ethics in public relations that go beyond simple compliance with professional codes and industry standards and that help organizations lead societal change.
The entrepreneurial mindset in entrepreneurship education: what can we learn from S-O-R models?
Authors: Larsen Inge Birkbak , Blenker Per , Neergaard Helle
Published: September 2023

Purpose

The aim of this paper is to examine the usefulness of the stimulus-organism-response (S-O-R) model for systematizing and further exploring the knowledge of the role of entrepreneurship education (EE) in fostering students' entrepreneurial mindset (EM). Current research studying the EM in an educational setting often fails to conceptualize this mindset and its attributes rigorously and to include epistemological considerations regarding how the authors can know whether a person has developed an EM or not.

Design/methodology/approach

The authors test the S-O-R model by combining it with a critical realist approach to develop a conceptual model for understanding the EM and its development in an educational setting.

Findings

The authors identify eight psychological constructs that represent markers of the EM. The authors further surface the multi-causal characteristic of learning in EE. The authors' model cannot be applied to detect causal relationships, but it is useful in exploring potential causal tendencies and plausible explanations of the mechanisms and circumstances of EE, which may, in concert, potentially foster the psychological attributes associated with an EM.

Originality/value

The paper addresses the often-overlooked epistemological considerations related to how the authors can know anything about psychological and theoretical constructs, such as the EM. A conscious discussion about how the authors can develop knowledge and insight about the EM and how individuals develop it is critical to justify a continued focus on the EM in EE.
Business model pivoting and digital technologies in turbulent environments
Authors: Balta Maria Elisavet , Papadopoulos Thanos , Spanaki Konstantina
Published: September 2023

Purpose

This paper aims to draw on the Dynamic Capabilities View to discuss how small and medium enterprises (SMEs) use digital technologies to develop digital capabilities that will enable them to change their current business model and trajectory, that is, to pivot-within turbulent environments, and subsequently to survive and grow.

Design/methodology/approach

The authors collected and analysed qualitative data from 26 SMEs in South-East England that have used digital technologies to pivot during the pandemic. The data was collected via in-depth semi-structured interviews. The authors analysed the data by creating first-order concepts, second-order themes, and aggregating dimensions.

Findings

The findings suggest that (1) digital technologies enable pivoting by facilitating the creation of the following digital capability types: “digital sensing”, “digital seizing” and “digital transforming”; (2) Each of these digital capability types is underpinned by micro-foundations (sub-capabilities) and shaped by the digital culture of the organisation. (3) these capabilities are triggered by the turbulent environment and the existing digital technologies, and are shaped by the digital culture.

Originality/value

The authors contribute to the literature of digital entrepreneurship as the authors illustrate (1) how the micro-foundations of digital capabilities, as facilitated by digital technologies, assist pivoting; and (2) the process from key activities during pivoting to second-order themes that represent micro-foundations to digital (dynamic) capabilities for pivoting in turbulent environments. The study highlights the importance of digital pivoting for businesses in the UK Southeast that have many aspirations for growth and innovation, whilst striving to address multiple challenges including digital divide and literacy, inflation and cost of living crisis, as well as supply chain issues.
Collaborative research competencies in supply chain management: the role of boundary spanning and reflexivity
Authors: Beaulieu Martin , Rebolledo Claudia , Lissillour Raphael
Published: September 2023

Purpose

This paper aims to investigate the competencies that researchers need to develop and employ for successful collaborative research.

Design/methodology/approach

The authors use a reflexive approach built on participant observation of six cases of collaborative research in public procurement and logistics.

Findings

The authors identify and explain two major competencies that are required for successful collaborative research. The first is boundary-spanning competence that represents the researchers' ability to move fluidly from the academic milieu to the practitioner's environment. The second is reflexivity competence that allows the researchers to learn from each collaborative research project they participate in and further improve their boundary-spanning competence.

Originality/value

This study goes beyond the list of skills for collaborative research reported in the literature to describe two major competencies that researchers should develop to perform successful collaborative research. This reflection may serve as a starting point for the development of a sociological understanding of the collaborative research field.
An optimal organizational excellence model for the public sector
Authors: Rahmati Mohammad Hossein , Jalilvand Mohammad Reza
Published: September 2023

Purpose

Current models of organizational excellence are appropriate for the private organizations. It is evident that if an appropriate model is not adopted, the process of excellence in the organizations fails and some dimensions of the organization get affected by unpredictable damages. This research aims to identify an appropriate excellence model for public organizations.

Design/methodology/approach

First, a comprehensive literature review was conducted to identify the excellence criteria and models. Second, the models were through an expert-oriented questionnaire, analyzed by the analytical hierarchy process (AHP) technique. Participants were experts in the two domains of excellence models and public sector management. A sample of 15 experts was selected using purposive sampling. In order to emphasize on reliability, 10 questionnaires were adopted for analysis.

Findings

The findings showed that the European Foundation for Quality Management (EFQM) model is the most appropriate model for excellence measurement in the public organizations based on the five selected indices.

Originality/value

The identification of a model for measuring organizational excellence for public sector can significantly contribute to existing literature on excellence measurement.
The clinical utility of Multidimensional Behavioral Health Screen
Authors: Davis Scott A. , Frayne Daniel , McSurdy Jessica , Franz Annabel O. , McCord David Mark
Published: September 2023

Purpose

In the USA, integrated care remains largely aspirational; a majority of Americans receive mental health care entirely within the primary medical care outpatient setting. A new instrument, the Multidimensional Behavioral Health Screen (MBHS) ( McCord, 2020) was developed specifically to address this gap by systematically screening for a broad array of mental health issues in every patient, every visit. The goal of this current feasibility study was to evaluate the perceptions of the primary medical care providers regarding the usefulness and practicality of the MBHS, a necessary step toward broad-based implementation.

Design/methodology/approach

The MBHS was given to 101 consenting patients in a primary medical outpatient setting, each of whom was then seen by one of six participating primary care providers (PCPs). Providers completed a brief survey rating the ease of use, understandability, helpfulness and perceived accuracy of the MBHS after each patient visit and a final summary survey at the conclusion of the study.

Findings

Ratings were very positive overall, and the MBHS was clearly preferred to the traditional screening measures (Patient Health Questionnaire-9 [PHQ-9] and Generalized Anxiety Disorder-7 [GAD-7]). Providers offered suggestions for improvement and particularly for implementation.

Research limitations/implications

The small sample size (101 patients and 6 PCPs) and limited geographical reach may limit generalizability. Surveying providers using similar methodology should be done with larger numbers of providers and more diverse primary medical care settings.

Practical implications

This study provides evidence that the MBHS may be significantly effective in operationalizing the integrated care model in United States (US) healthcare systems.

Social implications

The MBHS, a new behavioral health screening tool, was perceived by providers as useful in identifying mental health issues and guiding treatment decisions in the primary care setting.

Originality/value

This paper identifies a novel screening instrument that implements new and emerging models of psychological dysfunction in a practical way in primary medical care, making integrated care a reality rather than an aspiration.
Effects of chairman ownership on financing decisions: empirical evidence from GCC
Authors: Elmaasrawy Hamada Elsaid , Tawfik Omar Ikbal , Hussainey Khaled
Published: September 2023

Purpose

This study aims to examine the impacts of board chairman characteristics on the decision to finance with debts.

Design/methodology/approach

Based on historical data from 173 active nonfinancial firms listed on Gulf Cooperation Council (GCC) Stock Exchange Markets during 2012–2019, this research uses ordinary least squares (OLS) and dynamic system-generalized methods of moments to test its hypotheses. The final dataset comprises 1,384 firm-year observations from 10 major nonfinancial industry classifications.

Findings

Results indicate a negative impact of board chairman ownership on the decision to finance with retained earnings (RE). Negative effects of the chairman and chief executive officer (CEO) from the same family on the decision to finance with RE, whereas positive effects of the chairman and CEO from the same family on the decision to finance with debts are observed. In addition, a negative effect of the chairman from a royal family on the decision to invest with debts is found.

Research limitations/implications

Many board chairmen characteristics, such as age, gender, experience, education level, periodic change and ethnicity, are unaddressed. Financial decisions (FDs) are also limited to two decisions (internal financing with RE and external financing with debts).

Practical implications

Findings of this study provide an improved understanding of the role of chairman characteristics in FDs in GCC. Investors and lenders dealing with companies in GCC markets benefit from the authors' results because of the effects of chairman characteristics on FDs when making investment decisions in company stocks.

Originality/value

The study clarifies how each of the three board chairman characteristics (i.e. chairman ownership, chairman and CEO from the same family and the chairman from the royal family) affects FDs, especially the decisions to finance with debts and RE.