bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractClostridioides 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

AbstractHuman 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

AbstractThe 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

AbstractA 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

AbstractWild 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

1AbstractDesert 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.2TeaserIn 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

AbstractMate 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

ABSTRACTSingle-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

AbstractThe 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

PurposeBeginning 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/approachThe 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.FindingsResults 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/valueThis 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

PurposeThis 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/approachIn 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.FindingsEleven 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/valueWhile 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

PurposeThe 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/approachThis 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.FindingsRespondents 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 implicationsPractice implications include considerations for furthering moral entrepreneurship in organizations.Originality/valueThis 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

PurposeThe 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/approachThe 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.FindingsThe 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/valueThe 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.