bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple regulators control the biosynthesis of brasilicardin inNocardia terpenica
Authors: Wolański Marcin , Krawiec Michał , Nieselt Kay , Schwarz Tobias , Dere Dilek , Krismer Bernhard , Cano-Prieto Carolina , Gross Harald , Zakrzewska-Czerwińska Jolanta 
Published: June 2024

AbstractBrasilicardin A, BraA, is a secondary metabolite produced by the bacteriumNocardia terpenica, and a promising drug due to its potent immunosuppressive activity and low cytotoxicity. Currently, a semisynthetic approach confers production of a complete compound but suffers from insufficient heterologous biosynthesis of BraA intermediates used in the chemical semi-synthesis steps leading to only lab scale quantities of the compound. A better understanding of the involved gene expression regulatory pathways within the brasilicardin biosynthetic gene cluster, Bra-BGC, is a prerequisite to further improve production titers. However, the transcriptional regulation of the Bra-BGC has only been superficially analyzed, till now.In this study, we comprehensively analyze the functions of several unstudied transcriptional regulators, KstR, SdpR and OmpR, encoded within the close vicinity of the Bra-BGC, and delve into the role of the previously described cluster-situated activator Bra12. We present, that Bra12 and the novel regulator SdpR, bind several DNA sequences located in the promoter regions of the genes essential for BraA biosynthesis. Subsequently, we demonstrate the complex regulatory network through which both regulators are capable of controlling activity of those gene promoters and thus gene expression in Bra-BGC. Furthermore, using the heterologous producer strainAmycolatopsis japonicum, we present, that Bra12 and SdpR regulators play opposite roles in brasilicardin congener biosynthesis. Finally, we propose a comprehensive model of multilevel gene expression regulation in Bra-BGC and propose the roles of locally encoded transcriptional regulators.
Dimeric assembly of F1-like ATPase for the gliding motility ofMycoplasma
Authors: Toyonaga Takuma , Kato Takayuki , Kawamoto Akihiro , Miyata Tomoko , Kawakami Keisuke , Fujita Junso , Hamaguchi Tasuku , Namba Keiichi , Miyata Makoto 
Published: June 2024

AbstractRotary ATPases, including F1Fo- and V/A-ATPases, are molecular motors that exhibit rotational movements for energy conversion1. In the gliding bacterium,Mycoplasma mobile, a dimeric F1-like ATPase forms a chain structure with the glycolytic enzyme, phosphoglycerate kinase (PGK), within the cell2, which is proposed to drive the bacterial gliding motility2–4. However, the mechanisms of force generation and transmission remain unclear. Here, we present a 3.2 Å resolution structure of the dimeric ATPase complex obtained using electron cryomicroscopy (cryo-EM). Notably, the structure revealed an assembly distinct from that of known dimeric forms of F1Fo-ATPase5, despite containing conserved F1-ATPase structures. The two ATPase units were interconnected by GliD dimers, previously identified as MMOB16202,6. Gliβ, a homologue of the F1-ATPase catalytic subunit6, exhibited a specific N-terminal region that incorporates PGK into the complex. Structural conformations of the catalytic subunits, catalytically important residues, and nucleotide-binding pattern of the catalytic sites of the ATPase displayed strong similarities to F1-ATPase, suggesting a rotation based on the rotary catalytic mechanism conserved in rotary ATPases1,7–10. Overall, the cryo-EM structure underscores an evolutionary connection in the rotary ATPases and provides insights into the mechanism through which F1-like ATPase drives bacterial gliding motility.
Identification of cognate recombination directionality factors for large serine recombinases by virtual pulldown
Authors: Shin Heewhan , Holland Alexandria , Alsaleh Abdulrazak , Retiz Alyssa D. , Pigli Ying Z. , Taiwo-Aiyerin Oluwateniola T. , Reyes Tania Peña , Bello Adebayo J. , Olorunniji Femi J. , Rice Phoebe A. 
Published: June 2024

ABSTRACTIntegrases from the “large serine” family are simple, highly directional site-specific DNA recombinases that have great promise as synthetic biology and genome editing tools. Integrative recombination (mimicking phage or mobile element insertion) requires only integrase and two short (∼40 – 50) DNA sites. The reverse reaction, excisive recombination, does not occur until it is triggered by the presence of a second protein termed a Recombination Directionality Factor (RDF), which binds specifically to its cognate integrase. Identification of RDFs has been hampered due to their lack of sequence conservation and lack of synteny with the phage integrase gene. Here we use Alphafold2-multimer to identify putative RDFs for more than half of a test set of 98 large serine recombinases, and experimental methods to verify predicted RDFs for 4 of 5 integrases chosen as test cases. We find no universally conserved structural motifs among known and predicted RDFs, yet they are all predicted to bind a similar location on their cognate integrase, suggesting convergent evolution of function. Our methodology greatly expands the available genetic toolkit of cognate integrase – RDF pairs.
Differential growth enhancement followed by notable microbiota modulation in growing-finishing pigs byBacillus subtilisstrains ps4060, ps4100, and a 50:50 strain mixture
Authors: Song Jun Ho , Park Sung-Su , Kim In Ho , Cho Yangrae 
Published: June 2024

ABSTRACTA 50:50 blend of twoBacillus subtilisstrains positively impacted the productivity of finishing pigs. Given this observed effect, we hypothesized that each strain has distinct effects on weight gain and their influence on gut microbiota. In a 16-week test, 160 pigs were divided into four groups: basal diet,B. subtilisps4100,B. subtilisps4060, and 50:50 mixture supplemented. Subsequently, we compared body weight and fecal microbiota. Among the supplements, ps4100, ps4060, and the 50:50 mix yielded respective average daily weight gains (ADG) of 3.6%, 4.6%, and 3.9% by the 6th week. The weight difference was maintained through the 16th week. At the 11th week, the difference in α-diversity among the fecal microbiota was marginal, and 17 of 229 genera showed differential abundance between the control and either of the treatment groups. A total of 12 of the 17 genera, includingLactobacillus, showed differential abundance between the ps4100 and ps4060-fed groups, and onlyEubacteriumconsistently decreased in abundance in both the ps4100 and ps4060 groups. In comparison, microbial diversity was significantly different at the 16th week (p< 0.05), with 96 out of 229 genera exhibiting differential abundance. A total of 42 of the 96 genera exhibited similar patterns in both the ps4100 and ps4060 groups compared to the control group. Additionally, 236 of 687 microbial enzymes with differential abundance deduced from 16S rRNA reads showed similar differential abundance in both groups compared to the control group. We concluded that the overall microbial balance, rather than the dominance or significant decrease of a few specific genera, likely caused the enhanced ADG until the 11th week. Substantial changes in microbiota manifested at the 16th week did not cause dramatically increased ADG but were a consequence of weight gain and could positively affect animal physiology and health afterward.
Centrosome positioning independently of microtubule-based forces
Authors: Schaeffer Alexandre , Gazzola Morgan , Gelin Matthieu , Vianay Benoit , de Pascalis Chiara , Blanchoin Laurent , Théry Manuel 
Published: June 2024

AbstractThe regulation of centrosome position is central to the establishment of polarized cell functions. This process is thought to rely on the generation of mechanical forces along microtubules, the balance of which determines centrosome position. By studying these forces in adherent cells in culture, we found that neither pushing nor pulling forces propagate along microtubules to the centrosome. Inhibiting dyneins or disassembling microtubules did not disrupt the maintenance of the centrosome at the center of the cell. In contrast, the actomyosin contractile network appears to be responsible for the generation of a centripetal flow that drives the centrosome towards the center of the cell independently of the microtubules. Furthermore, we found that centering of the centrosome depends more on the reorganization of cell shape around the centrosome than on an effective centrosome displacement throughout the cytoplasm. Interestingly, despite their lack of mechanical role, microtubules appear to direct this remodeling of cell shape. This revised view of centrosome positioning offers a new perspective for understanding the establishment of cell polarity.
Cyclical MinD membrane affinity differences are not necessary for MinD gradient formation inBacillus subtilis
Authors: Bohorquez Laura C. , Strahl Henrik , Marenduzzo Davide , Thiele Martin J. , Bürmann Frank , Hamoen Leendert W. 
Published: June 2024

ABSTRACTProteins can diffuse micrometers in seconds, yet bacterial cells are able to maintain stable protein gradients. The best studied bacterial protein gradient is the Min system ofEscherichia coli. In rod-shaped bacteria the MinCD proteins prevent formation of minicells by inhibiting FtsZ polymerization close to the cell poles. InE. colithese proteins oscillate between cell poles within a minute, resulting in an increased MinCD concentration at the poles. This oscillation is caused by the interaction between MinD and the protein MinE, which form an ATP-driven reaction-diffusion system, whereby the ATPase MinD cycles between a monomeric cytosolic and a dimeric membrane attached states.Bacillus subtilisalso has MinCD, but lacks MinE. In this case MinCD form a static gradient that requires the transmembrane protein MinJ, located at cell poles and cell division sites. A recent reaction-diffusion model was successful in recreating the MinD gradient inB. subtilis, assuming that MinD cycles between cytosol and membrane, like inE. coli. Here we show that the monomeric and dimeric states ofB. subtilisMinD have comparable membrane affinities, that MinD interacts with MinJ as a dimer, and that MinJ is not required for membrane localization of MinD. Based on these new findings we tested different models, using kinetic Monte Carlo simulations, and found that a difference in diffusion rate between the monomer and dimer, rather than a difference in membrane affinity, is important forB. subtilisMinCD gradient formation.IMPORTANCEProteins can diffuse micrometers in seconds, yet bacterial cells are able to maintain stable protein gradients. One of the best studied examples is the membrane associated MinD protein gradient inEscherichia coli. This oscillating gradient requires cycling of MinD between a monomeric cytosolic and a dimeric membrane attached state.Bacillus subtilisalso has a Min system, but in this case MinD forms a static gradient. Mathematical models have been successful in recreating the MinD gradient inB. subtilis, using anE. coli-like membrane attachment cycle of MinD. Here we show that, in contrast to theE. colisituation, the monomeric and dimeric state ofB. subtilisMinD have comparable membrane affinities. Using this and other information, we tested Monte Carlo simulations and found that a difference in diffusion rate between MinD monomer and dimer, rather than a difference in membrane affinity, is important for MinD gradient formation inB. subtilis.
The interplay between Mobilome and Resistome inStaphylococcus aureus
Authors: Contarin Rachel , Drapeau Antoine , François Pauline , Madec Jean-Yves , Haenni Marisa , Dordet-Frisoni Emilie 
Published: June 2024

AbstractAntibiotic resistance genes (ARGs) inStaphylococcus aureuscan disseminate vertically through successful clones, but also horizontally through the transfer of genes conveyed by mobile genetic elements (MGEs). The underexplored MGE/ARG associations in S. aureusfavor the emergence of multidrug-resistant clones, posing a significant threat to human and animal health.This study investigated the interplay between the mobilome, encompassing MGEs, and the resistome, the collection of ARGs, in more than 10,000S. aureusgenomes from human and animal sources. The analysis revealed a remarkable diversity of MGEs and ARGs, with plasmids and transposons being the main carriers of resistance genes. Numerous MGE/ARG associations were identified, suggesting that MGEs play a critical role in the dissemination of resistance. A high degree of similaritywas observed in MGE/ARG associations between human and animal isolates, highlighting the potential for unrestricted spread of ARGs between hosts. While clonal expansion is a major driver of resistance dissemination inS. aureus, our results showed that MGEs and their associated ARGs can spread across different strain types (STs), favoring the evolution of these clones and their adaptation in selective environments. The high variability of MGE/ARG associations within individual STs and the ir spread across several STs highlight the crucial role of MGEs in shaping theS. aureusresistome.Overall, this study provides valuable insights into the complex interplay between MGEs and ARGs inS. aureus, emphasizing the need to elucidate the mechanisms governing the epidemic success of MGEs, particularly those implicated in ARG transfer.ImportanceThe research presented in this article highlights the crucial importance of understanding the interactions between mobile genetic elements (MGEs) and antibiotic resistance genes (ARGs) carried byStaphylococcus aureus, a versatile bacterium that can be both a harmless commensal and a dangerous pathogen for humans and animals.S. aureusstrains represent a major threat due to their ability to rapidly acquire and disseminate ARGs. By analyzing a large dataset ofS. aureusgenomes, we highlighted the substantial role of MGEs, in particular plasmids and transposons, in the dissemination of ARGs within and betweenS. aureuspopulations, bypassing the host barrier. Given that multidrug-resistantS. aureusstrains are classified as a high-prioritypathogenby global health organizations, this knowledge is crucial for understanding the complex dynamics of transmission of antibiotic resistance in this species.
Reading Outside the Lines: A Systematic Approach for Detecting Bias in Scientific Communications
Authors: Osborne Melisa , McKenna TJ , Crawford Felicity , Rueger Theresa , Shah Barkha , Gott Mae Rose , Labadorf Adam 
Published: June 2024

ABSTRACTConsciousness of the social impact of science and the potential biases of its authors is critical to understanding, interpreting, and using scientific findings responsibly. This is especially true for sciences concerned with human health and behavior, where societal and unconscious biases may reinforce existing inequities and discriminatory practices. Considering backgrounds and biases, we may notice bias influencing scientists’ methodological choices and conclusions, even when a work is otherwise scientifically sound. To this end, we created the pedagogical tool Finding inEquity in LIterature and eXperimentation (FELIX). FELIX is a tool that systematizes the detection of bias and subjectivity in scientific communications by using a three-phase progression of (i) Annotation, (ii) Analysis and (iii) Synthesis, where students form a unified argument about the text with a focus on its relationship to social or ethical context. Results from a mixed methods approach indicated the efficacy of our approach in supporting student learning related to reading comprehension, critical thinking skills, and in understanding the social and ethical implications of the research they were reading. We put forward FELIX as a universal method for training students in the reading of scientific communications and as a tool for addressing systemic inequities in science and science education.
Salience signaling and stimulus scaling of ventral tegmental area glutamate neuron subtypes
Authors: McGovern Dillon J. , Phillips Alysabeth , Ly Annie , Prévost Emily D. , Ward Lucy , Siletti Kayla , Kim Yoon Seok , Fenno Lief E. , Ramakrishnan Charu , Deisseroth Karl , Ford Christopher P. , Root David H. 
Published: June 2024

ABSTRACTVentral tegmental area (VTA) glutamatergic neurons participate in reward, aversion, drug-seeking, and stress. Subsets of VTA VGluT2+ neurons are capable of co-transmitting glutamate and GABA (VGluT2+VGaT+ neurons), transmitting glutamate without GABA (VGluT2+VGaT- neurons), or co-transmitting glutamate and dopamine (VGluT2+TH+ neurons), but whether these molecularly distinct subpopulations show behavior-related differences is not wholly understood. We identified that neuronal activity of each VGluT2+ subpopulation is sensitive to reward value but signaled this in different ways. The phasic maximum activity of VGluT2+VGaT+ neurons increased with sucrose concentration, whereas VGluT2+VGaT- neurons increased maximum and sustained activity with sucrose concentration, and VGluT2+TH+ neurons increased sustained but not maximum activity with sucrose concentration. Additionally, VGluT2+ subpopulations signaled consummatory preferences in different ways. VGluT2+VGaT- neurons and VGluT2+TH+ neurons showed a signaling preference for a behaviorally-preferred fat reward over sucrose, but in temporally-distinct ways. In contrast, VGluT2+VGaT+ neurons uniquely signaled a less behaviorally-preferred sucrose reward compared with fat. Further experiments suggested that VGluT2+VGaT+ consummatory reward-related activity was related to sweetness, partially modulated by hunger state, and not dependent on caloric content or behavioral preference. All VGluT2+ subtypes increased neuronal activity following aversive stimuli but VGluT2+VGaT+ neurons uniquely scaled their magnitude and sustained activity with footshock intensity. Optogenetic activation of VGluT2+VGaT+ neurons during low intensity footshock enhanced fear-related behavior without inducing place preference or aversion. We interpret these data such that VTA glutamatergic subpopulations signal different elements of rewarding and aversive experiences and highlight the unique role of VTA VGluT2+VGaT+ neurons in enhancing the salience of behavioral experiences.
Field, frequency, and temperature dependencies of the surface resistance of nitrogen diffused niobium superconducting radio frequency cavities
Authors: Dhakal P. , Khanal B. D. , Gurevich A. , Ciovati G. 
Published: June 2024

We investigate the rf performance of several single-cell superconducting radio-frequency cavities subjected to low temperature heat treatment in nitrogen environment. The cavities were treated at temperature 120–165 °C for an extended period of time (24–48 h) either in high vacuum or in a low partial pressure of ultrapure nitrogen. The improvement in Q0 with a Q rise was observed when nitrogen gas was injected at ∼300 °C during the cavity cooldown from 800 °C and held at 165 °C, without any degradation in accelerating gradient over the baseline performance. The treatment was applied to several elliptical cavities with frequency ranging from 0.75 to 3.0 GHz, showing an improved quality factor as a result of low temperature nitrogen treatments. The Q rise feature is similar to that achieved by nitrogen alloying Nb cavities at higher temperature, followed by material removal by electropolishing. The surface modification was confirmed by the change in electronic mean free path and tuned with the temperature and duration of heat treatment. The decrease of the temperature-dependent surface resistance with increasing rf field, resulting in a Q rise, becomes stronger with increasing frequency and decreasing temperature. The data suggest a crossover frequency of ∼0.95  GHz above that the Q rise phenomenon occurs at 2 K. Some of these results can be explained qualitatively with an existing model of intrinsic field-dependence of the surface resistance with both equilibrium and nonequilibrium quasiparticle distribution functions. The change in the Q slope below 0.95 GHz may result from masking contribution of trapped magnetic flux to the residual surface resistance.

Published by the American Physical Society
2024
Nuclear-matter saturation and symmetry energy within
Δ
-full chiral effective field theory
Authors: Jiang W. G. , Forssén C. , Djärv T. , Hagen G. 
Published: June 2024

Nuclear saturation and the symmetry energy are key properties of low-energy nuclear physics that depend on fine details of the nuclear interaction. The equation of state around saturation is also an important anchor for extrapolations to higher densities and studies of neutron stars. Here we develop a unified statistical framework that uses realistic nuclear forces to link the theoretical modeling of finite nuclei and infinite nuclear matter. We construct fast and accurate emulators for nuclear-matter observables and employ an iterative history-matching approach to explore and reduce the enormous parameter domain of Δ-full chiral interactions. We perform rigorous uncertainty quantification and find that model calibration including O16 observables gives saturation predictions that are more precise than those that only use few-body data.

Published by the American Physical Society
2024
Representation of women and people of color on nonprofit boards and CEO gender and race
Authors: Lee Young-joo 
Published: June 2024

PurposeThis study examines how the representation of women and people of color on nonprofit boards relates to CEO gender and race.Design/methodology/approachThis study uses the 2020 data of 501(c)(3) nonprofit organizations in a Southeastern U.S. state. It employs the seemingly unrelated bivariate probit regression to simultaneously estimate the two equations for CEO gender and race.FindingsThe findings show that the proportion of board members of color is positively associated with having a CEO of color and a female CEO. The proportion of female board members is positively associated with having a female CEO, but not with having a CEO of color.Practical implicationsThe lack of a positive connection between women’s representation on the board and having a CEO of color may be attributable to the pervasive and systematic Whiteness in nonprofit leadership. The findings suggest that nonprofit boards reflect on the current executive hiring policies and practices to address existing racial biases or barriers.Originality/valueThis study’s findings reveal that the descriptive representation of women and people of color in the governing board is closely linked to their substantive representation in the form of selecting a woman or a person of color as the CEO. The findings also suggest an interconnection between the representation of people of color on the board and having a female CEO. However, women’s representation on the board is not related to having a CEO of color.
The influence of human resource management policies on employee behaviour related outcomes and organisational resilience during COVID-19
Authors: Baird Kevin , Tung Amy , Phan Thanh , Bhuyan Mohammed 
Published: June 2024

PurposeThis study examines the effect of Human Resource Management (HRM) policies in respect to workplace flexibility and employee empowerment on two employee behaviour related outcomes (employee organisational commitment (EOC) and collegiality) and organisational resilience during the COVID-19 pandemic.Design/methodology/approachData were collected using an online survey questionnaire managed by Qualtrics. The questionnaire was distributed to the lower, middle and senior managers of 1,000 Australian organisations with 337 responses used in the analysis.FindingsThe findings indicate that workplace flexibility exhibits a direct and indirect (through collegiality) significant positive association with organisational resilience, and employee empowerment exhibits a direct and indirect (through both EOC and collegiality) significant positive association with organisational resilience.Originality/valueThe results highlight the importance of implementing desirable HRM policies in respect to empowering employees and enhancing workplace flexibility due to their role in facilitating organisational resilience both directly and indirectly through their influence on employee behaviour related outcomes, specifically EOC and collegiality.