bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial heterozygosity promotes survival under multidrug selection
Authors: Shitut Shraddha , van Dijk Thomas , Claessen Dennis , Rozen Daniel 
Published: May 2024

ABSTRACTAlthough bacterial cells typically contain a single chromosome, some species are naturally polyploid and carry multiple copies of their chromosome. Polyploid chromosomes can be identical or heterogeneous, the latter giving rise to bacterial heterozygosity. While the benefits of heterozygosity are well studied in eukaryotes, its consequences in bacteria are unknown. Here we examine this question in the context of antibiotic resistance to understand how bacterial heterozygosity affects bacterial survival. Using a cell wall deficient model system in the actinomyceteKitasatospora viridifaciens, we found that heterozygous cells containing different chromosomes expressing different antibiotic resistance markers persist across a broader range of antibiotic concentrations. Recombinant cells containing the same resistance genes on a single chromosome also survive these conditions, but these cells pay a significant fitness cost due to constitutive expression of these genes. By contrast, heterozygous cells mitigate these costs by flexibly adjusting the ratio of their different chromosomes, thereby allowing rapid responses in temporally and spatially variable environments. Our results provide evidence that bacterial heterozygosity can increase adaptive plasticity in bacterial cells, in a similar manner to the evolutionary benefits provided by multicopy plasmids in bacteria.Graphical abstractHeterozygotic bacterial cells (polyploid with multiple chromosome types) can persist across a wider range of conditions than homozygotic cells.Heterozygous cells can adaptively adjust chromosomal frequencies in response to external conditionsFlexibly adjusting chromosome ratios enables heterozygous cells to mitigate the costs of antibiotic resistance and allows rapid responses to temporally and spatially variable environmentsHeterozygosity can increase adaptive plasticity in bacterial cells, in a similar manner to the evolutionary benefits provided by multicopy plasmids.
A meta reinforcement learning account of behavioral adaptation to volatility in recurrent neural networks
Authors: Tuzsus D. , Pappas I. , Peters J. 
Published: May 2024

AbstractNatural environments often exhibit various degrees of volatility, ranging from slowly changing to rapidly changing contingencies. How learners adapt to changing environments is a central issue in both reinforcement learning theory and psychology. For example, learners may adapt to changes in volatility by increasing learning if volatility increases, and reducing it if volatility decreases. Computational neuroscience and neural network modeling work suggests that this adaptive capacity may result from a meta-reinforcement learning process (implemented for example in the prefrontal cortex), where past experience endows the system with the capacity to rapidly adapt to environmental conditions in new situations. Here we provide direct evidence for a meta-reinforcement learning account of adaptation to environmental volatility. Recurrent neural networks (RNNs) were trained on a restless four-armed bandit reinforcement learning problem under three different training regimes (low volatility training only, medium volatility training only, or meta-volatility training across a range of volatilities). We show that, in contrast to RNNs trained in the low volatility regime, RNNs trained under the medium or meta-volatility regimes exhibited a superior adaption to environmental volatility. This was reflected in a better performance, and computational modeling of the network’s behavior revealed a more adaptive adjustment of learning and exploration to varying levels of volatility during test. Results extend the meta-RL account to volatility adaptation and confirm past experience as a crucial factor of adaptive decision-making.
Dopamine transporter threonine-53 phosphorylation dictates kappa opioid receptor mediated locomotor suppression and conditioned place aversion via transporter upregulation
Authors: Varman Durairaj Ragu , Jayanthi Lankupalle D. , Ramamoorthy Sammanda 
Published: May 2024

AbstractDynorphin (DYN)/kappa opioid receptor (KOR) activation contributes to aversion, dysphoria, sedation, depression, and enhanced psychostimulant-rewarding effects, which have been attributed to the inhibition of dopamine (DA) release. DYN fibers synapse onto DA terminals which express both KOR and dopamine transporter (DAT). DAT activity is critical in the regulation of DA dynamics and dopaminergic neurotransmission. Previously, we demonstrated that KOR agonists upregulate DAT activity via ERK1/2 signaling involving phospho-Thr53 DAT (pT53-DAT). However, whether pT53-DAT is involved in KOR-mediated DAT regulation in-vivo and whether such phenomenon contributes to the behavioral effects of KOR agonism are unknown. Here, we investigated the role of endogenous pT53-DAT in KOR-mediated DAT regulation and the effect of KOR agonists on locomotor suppression and aversive behaviors using DAT-Ala53 knock-in mice expressing DAT carrying non-phosphorylatable Ala at position 53 replacing Thr. Acute systemic administration of KOR agonist, U69593 resulted in KOR antagonist-sensitive increases in DAT activity in parallel to increases in pT53-DAT, and DAT Vmaxand surface expression in the ventral and dorsal striatum (containing the nucleus accumbens and caudate putamen respectively) of WT, but not DAT-Ala53 mice. KOR agonists produced conditioned place aversion (CPA) and locomotor suppression in WT but not DAT-Ala53 mice. However, both WT and DAT-Ala53 mice exhibited similar lithium chloride-induced CPA and morphine-induced conditioned place preference (CPP). These findings provide the first evidence that locomotor suppression and aversive responses to KOR agonists manifest due to the modulation of DAT activity via DAT-T53 phosphorylation establishing a causal relationship of pT53-DAT in KOR-mediated DAT regulation and KOR agonist-induced adverse effects.
The vibriophage-encoded inhibitor OrbA abrogates BREX-mediated defense through the ATPase BrxC
Authors: Oshiro Reid T , Dunham Drew T , Seed Kimberley D 
Published: May 2024

AbstractBacteria and phages are locked in a co-evolutionary arms race where each entity evolves mechanisms to restrict the proliferation of the other. Phage-encoded defense inhibitors have proven powerful tools to interrogate how defense systems function. A relatively common defense system is BREX (Bacteriophage exclusion); however, how BREX functions to restrict phage infection remains poorly understood. A BREX system encoded by the SXT integrative and conjugative element,VchInd5, was recently identified inVibrio cholerae, the causative agent of the diarrheal disease cholera. The lytic phage ICP1 that co-circulates withV. choleraeencodes the BREX inhibitor OrbA, but how OrbA inhibits BREX is unclear. Here, we determine that OrbA inhibits BREX using a unique mechanism from known BREX inhibitors by directly binding to the BREX component BrxC. BrxC has a functional ATPase domain that, when mutated, not only disrupts BrxC function but also alters how BrxC multimerizes. Furthermore, we find that OrbA binding disrupts BrxC-BrxC interactions. We determine that OrbA cannot bind BrxC encoded by the distantly related BREX system encoded by the SXTVchBan9, and thus fails to inhibit this BREX system that also circulates in epidemicV. cholerae. Lastly, we find that homologs of theVchInd5 BrxC are more diverse than the homologs of theVchBan9 BrxC. These data provide new insight into the function of the BrxC ATPase and highlight how phage-encoded inhibitors can disrupt phage defense systems using different mechanisms.ImportanceWith renewed interest in phage therapy to combat antibiotic-resistant pathogens, understanding the mechanisms bacteria use to defend themselves against phages and the counter-strategies phages evolve to inhibit defenses is paramount. Bacteriophage exclusion (BREX) is a common defense system with few known inhibitors. Here, we probe how the vibriophage-encoded inhibitor OrbA inhibits the BREX system ofVibrio cholerae, the causative agent of the diarrheal disease cholera. By interrogating OrbA function, we have begun to understand the importance and function of a BREX component. Our results demonstrate the importance of identifying inhibitors against defense systems, as they are powerful tools for dissecting defense activity and can inform strategies to increase the efficacy of some phage therapies.
X-ray crystallographic analyses of 14 IPMK inhibitor complexes
Authors: Wang Huanchen , Blind Raymond D. , Shears Stephen B. 
Published: May 2024

AbstractInositol polyphosphate multikinase (IPMK) is a ubiquitously expressed kinase that has been linked to several cancers. Here, we report 14 new co-crystal structures (1.7Å - 2.0Å resolution) of human IPMK complexed with various IPMK inhibitors developed by another group. The new structures reveal two ordered water molecules that participate in hydrogen-bonding networks, and an unoccupied pocket in the ATP-binding site of human IPMK. New Protein Data Bank (PDB) codes of these IPMK crystal structures are:8V6W(1.95Å),8V6X(1.75Å),8V6Y(1.70Å),8V6Z(1.85Å),8V70(1.85Å),8V71(1.70Å),8V72(2.0Å),8V73(1.90Å),8V74(1.85Å),8V75(1.85Å),8V76(1.95Å),8V77(1.95Å),8V78(1.95Å),8V79(1.95Å).
Prediction of pathological subthalamic nucleus beta burst occurrence in Parkinson’s disease
Authors: Abdi-Sargezeh Bahman , Shirani Sepehr , Sharma Abhinav , Green Alexander , Akram Harith , Zrinzo Ludvic , Limousin Patricia , Foltynie Tom , Denison Timothy , Tan Huiling , Litvak Vladimir , Oswal Ashwini 
Published: May 2024

AbstractThe cortico-basal ganglia network in Parkinson’s disease (PD) is characterized by the emergence of transient episodes of exaggerated beta frequency oscillatory synchrony known as bursts. Although it is well established that bursts of prolonged duration associate closely with motor impairments, the mechanisms leading to burst initiation remain poorly understood. Crucially, it is unclear whether there are features of basal ganglia activity which reliably predict burst onset. Current adaptive Deep Brain Stimulation (aDBS) approaches can only reactively deliver stimulation following burst detection and are unable to stimulate proactively to prevent burst onset. The discovery of predictive biomarkers could allow for such proactive stimulation, thereby offering potential for improvements in therapeutic efficacy. Here, using deep learning, we show that the timing of subthalamic nucleus (STN) beta bursts can be accurately predicted up to 60 ms prior to onset. Furthermore, we highlight that a dip in the beta amplitude - which is likely to be indicative of a phase reset of oscillatory populations occurring between 80-100 ms prior to burst onset - is a predictive biomarker for burst occurrence. These findings demonstrate proof-of-principle for the feasibility of beta burst prediction for DBS and provide insights into the mechanisms of burst initiation.
Native β-barrel substrates pass through two shared intermediates during folding on the BAM complex
Authors: Santos Thiago M. A. , Thomson Benjamin D. , Marquez Melissa D. , Pan Lydia , Monfared Tabasom H , Kahne Daniel E. 
Published: May 2024

AbstractThe assembly of β-barrel proteins into membranes is mediated by the evolutionarily conserved BAM complex. InEscherichia coli, BAM folds numerous substrates which vary considerably in size and shape. How BAM is able to efficiently fold such a diverse array of β-barrel substrates is not clear. Here, we develop a disulfide crosslinking method to trap native substrates in vivo as they fold on BAM. By placing a cysteine within the luminal wall of the BamA barrel as well as in the substrate β-strands, we can compare the residence time of each substrate strand within the BamA lumen. We validated this method using two defective, slow-folding substrates. We used this method to characterize stable intermediates which occur during folding of two structurally different native substrates. Strikingly, these intermediates occur during identical stages of folding for both substrates: soon after folding has begun, and just before folding is completed. We suggest that these intermediates arise due to barriers to folding that are common between β-barrel substrates, and that the BAM catalyst is able to fold so many different substrates because it addresses these common challenges.Significance StatementThe outer membrane of Gram-negative bacteria is a barrier which protects these organisms from many antimicrobial agents. Here, we study the machine responsible for folding and inserting integral β-barrel proteins into the membrane: BAM. Outer membrane integrity and cell viability is dependent on the proper function of BAM. Here we show that stable intermediates exist on the folding pathway of native substrates. We also show that mutant substrates that increase the stability of these native intermediates can stall during folding. This creates permeability defects that can be exploited by antibiotics that normally do not cross the outer membrane. These observations could enable the design of strategies to combat Gram-negative pathogens.
Structural basis for catalysis and selectivity of phospholipid synthesis by eukaryotic choline-phosphotransferase
Authors: Roberts Jacquelyn R. , Horibata Yasuhiro , Kwarcinski Frank E. , Lam Vinson , Raczkowski Ashleigh M. , Hubbard Akane , White Betsy , Sugimoto Hiroyuki , Tall Gregory G. , Ohi Melanie D. , Maeda Shoji 
Published: May 2024

AbstractPhospholipids are the most abundant component in lipid membranes and are essential for the structural and functional integrity of the cell. In eukaryotic cells, phospholipids are primarily synthesizedde novothrough the Kennedy pathway that involves multiple enzymatic processes. The terminal reaction is mediated by a group of cytidine-5’-diphosphate (CDP)-choline /CDP-ethanolamine-phosphotransferases (CPT/EPT) that use 1,2-diacylglycerol (DAG) and CDP-choline or CDP-ethanolamine to produce phosphatidylcholine (PC) or phosphatidylethanolamine (PE) those are the main phospholipids in eukaryotic cells. Here we present the structure of the yeast CPT1 in multiple substrate-bound states. Structural and functional analysis of these binding-sites reveal the critical residues for the DAG acyl-chain preference and the choline/ethanolamine selectivity. Additionally, we present the structure in complex with a potent inhibitor characterized in this study. The ensemble of structures allows us to propose the reaction mechanism for phospholipid biosynthesis by the family of CDP-alcohol phosphatidyltransferases (CDP-APs).
QGSJET-III model of high energy hadronic interactions. II. Particle production and extensive air shower characteristics
Authors: Ostapchenko Sergey 
Published: May 2024

The hadronization procedure of the QGSJET-III Monte Carlo (MC) generator of high energy hadronic interactions is discussed. Selected results of the model, regarding production spectra of secondary particles, are presented in comparison to experimental data and to the corresponding predictions of the QGSJET-II-04 MC generator. The model is applied to calculations of basic characteristics of extensive air showers initiated by cosmic ray interactions in the atmosphere and the results are compared to predictions of other MC generators of cosmic ray interactions.

Published by the American Physical Society
2024
Low-mass dark sector searches with deuteron photodisintegration
Authors: Mommers Cornelis J. G. , Vanderhaeghen Marc 
Published: May 2024

Recent years have seen much activity in searches for dark-sector messenger particles in the 10–100 MeV mass range, especially in view of a potential new light boson conjectured by the ATOMKI Collaboration, X17. Under the assumption that the messenger particle has definite parity and either zero or unit spin, quite stringent bounds already exist on its coupling to electrons and protons. Equally stringent bounds on the neutron coupling do not exist yet, but are nonetheless desirable. We explore how measurements of deuteron photodisintegration with a quasifree neutron can yield bounds on the neutron coupling, and compute projections for a potential measurement at the low-energy high-intensity electron scattering experiment MAGIX@MESA. The projected bounds are found to be competitive for an axial-vector or pseudoscalar scenario, but not for a vector or scalar scenario.

Published by the American Physical Society
2024
Fermions, quantum gravity, and holography in two dimensions
Authors: Asaduzzaman Muhammad , Catterall Simon , Samlodia Abhishek 
Published: May 2024

We study a model comprising N flavors of Kähler Dirac fermion propagating on a triangulated two-dimensional disk which is constrained to have a negative average bulk curvature. Dirichlet boundary conditions are chosen for the fermions. Quantum fluctuations of the geometry are included by summing over all possible triangulations consistent with these constraints. We show in the limit N→∞ that the partition function is dominated by a regular triangulation of two-dimensional hyperbolic space. We use strong coupling expansions and Monte Carlo simulation to show that in this limit boundary correlators of the fermions have a power law dependence on boundary separation as one expects from holography. However, we argue that this behavior breaks down for any finite number of massive fields in the thermodynamic limit and quantum fluctuations of the bulk geometry drive the theory into a nonholographic phase. In contrast, for massless fermions, we find evidence that the boundary is conformal even for finite N. This is consistent with theoretical results in quantum Liouville theory.

Published by the American Physical Society
2024
Multi-GeV Electron Acceleration in Wakefields Strongly Driven by Oversized Laser Spots
Authors: Põder K. , Wood J. C. , Lopes N. C. , Cole J. M. , Alatabi S. , Backhouse M. P. , Foster P. S. , Hughes A. J. , Kamperidis C. , Kononenko O. , Mangles S. P. D. , Palmer C. A. J. , Rusby D. , Sahai A. , Sarri G. , Symes D. R. , Warwick J. R. , Najmudin Z. 
Published: May 2024

Experiments were performed on laser wakefield acceleration in the highly nonlinear regime. With laser powers P<250  TW and using an initial spot size larger than the matched spot size for guiding, we were able to accelerate electrons to energies Emax>2.5  GeV, in fields exceeding 500  GV m−1, with more than 80 pC of charge at energies E>1  GeV. Three-dimensional particle-in-cell simulations show that using an oversized spot delays injection, avoiding beam loss as the wakefield undergoes length oscillation. This enables injected electrons to remain in the regions of highest accelerating fields and leads to a doubling of energy gain as compared to results from using half the focal length with the same laser.

Published by the American Physical Society
2024
The art of living together: space mining ecosystem, sustainability and accountability
Authors: Lee Yeolan , Fong Eric A. 
Published: May 2024

PurposeA major obstacle regarding the measurement of an organization's sustainability and accountability in the space economy is defining the context and boundaries of commercial activity in outer space. Here, we introduce an ecosystem framework to address this obstacle. We utilize this framework to analyze the space mining sector. Our ecosystem framework sets the space mining sector's boundaries and helps a firm identify key stakeholders, activities, policies, norms and common pool resources in that sector and the interactions between them; a significant step in structuring how to measure space sustainability and accountability.Design/methodology/approachBorrowing theories and perspectives from a wide range of academic fields, this paper conducts a comprehensive context analysis of the space mining ecosystem.FindingsUsing our ecosystem framework to define the context and set boundaries for the space mining sector allowed us to identify sustainability-related issues in the sector and offer roadmaps to develop sustainability measures and standards.Originality/valueTo the best of the authors’ knowledge, this is one of the first papers to introduce a framework to define boundaries in the global space economy and provides a tool to understand, measure and evaluate the space mining sector's environmental, social and economic issues.
Assessing the predictive validity of brand-sustainability-self-congruence on consumer behavior and subjective well-being
Authors: Kumagai Ken 
Published: May 2024

PurposeThis research extends self-congruity theory and assesses the predictive validity of the triad personality congruence among brand, brand-related sustainability initiatives (BSI) and self-concept (BSSC: brand-sustainability-self-congruence) on consumers’ brand evaluation.Design/methodology/approachThree studies assessed BSSC using the brand personality scale (BPS) and the direct congruence measure (DCM). Through moderated mediation analyses, BSSC effects were examined on consumers’ behavioral intention, behavior and subjective well-being (SWB). The mediating role of brand trust and the moderating role of brand/BSI types and consumer characteristics were also assessed.FindingsBSSC increased consumers’ brand trust, behavioral intention, behavior and SWB. Data based on BPS revealed impactful attributes that increase/decrease BSSC levels across brand-BSI combinations and the moderating role of sustainability involvement and income to enhance BSSC effects. BSSC was particularly effective, according to DCM.Practical implicationsFor BSI planning, strategic consideration of BSSC based on both BPS and DCM is recommended. Thus, managers may predict the psychological impact of BSI and align its attributes to increase consumers’ brand evaluation.Originality/valueIn the sustainable marketing context, this research discusses BSSC – triad personality congruence – based on BPS and DCM and its predictive effects on consumers’ short-term brand evaluation, their actual behavior and SWB, a long-term life evaluation. The results imply a possible variation in consumers’ information processing according to the congruence measurement approach. Thus, it is relevant to the research on self-congruity, sustainability, marketing, consumer psychology/behavior and well-being.
Vulnerability, resilience and empowerment: the tripartite typology for addressing modern slavery in global value chains
Authors: Kubacki Krzysztof , Szablewska Natalia , Siemieniako Dariusz , Brennan Linda 
Published: May 2024

Purpose
Modern slavery in global value chains is an emerging topic of interest across various fields, including in international business, but is often fragmented in its approach. This study aims to provide a practical framework for studying relationships between participants in global value chains by exploring the nexus of three concepts – vulnerability, resilience and empowerment (VRE) – in the context of modern slavery.

Design/methodology/approach
This article offers a deductive thematic analysis of 51 empirical and conceptual business research studies on modern slavery in global value chains published until mid-2021 according to the three categories of interest at the micro (within individuals and organisations), meso (between individuals and organisations) and macro (structural) levels.

Findings
The findings have informed the development of three themes, each of which is an opportunity for future research with clear policy implications: a reductionist approach to vulnerability obscures its complexity; externalising the empowerment process and locating it outside of the agency of workers serves to further disempower them; and focusing exclusively on organisational resilience conceals the essentiality of resilience within individuals, communities and societies.

Originality/value
This article is among the first to extend the focus of business literature on modern slavery in global value chains beyond its current largely facile engagement with VRE, offering an original descriptive VRE typology to engage with the nexus between these three concepts.