bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacteria-induced activation of a fungal silent gene cluster is controlled by histone deacetylase Sirtuin E
Authors: Jäger Nils , Rosin Maira , Stroe Maria C. , Brakhage Axel A. , Heinzel Thorsten 
Published: December 2023

AbstractFilamentous fungi encode an untapped reservoir of natural products whose biosynthesis enzymes are often encoded by gene clusters. The majority of these gene clusters are only activated under distinct environmental conditions such as the presence of distinct neighbouring microorganisms but not under standard laboratory conditions. Previously, we provided evidence for such a scenario with the specific activation of the silentorsgene cluster in the filamentous fungusAspergillus nidulansby the bacteriumStreptomyces rapamycinicus. The bacterium triggered the activation of the GcnE histone acetyltransferase that acetylated histone 3 in nucleosomes of theorsgene cluster and thebasRtranscription factor, and thereby the gene cluster. The inducing compound was shown to be the bacterial arginoketide azalomycin F. Here, by inhibitor studies with the pan-sirtuin inhibitor nicotinamide (NAM) the involvement of a sirtuin HDAC was implied. Accordingly, deletion of all six putative sirtuin-encoding genes (sirA-EandhstA) revealed that only deletion ofsirEled to production of orsellinic acid byA. nidulanswithout the need of the bacterium. Also other effects on growth and colony morphology due to NAM were phenocopied by thesirEdeletion mutant. Addition of NAM did not compensate for the loss of the BasR transcription factor required for activation of theorsgene cluster. Collectively, SirE is the negative regulator of the bacteria-induced activation of theorsBGC. In line, addition of NAM to monocultures ofAspergillus mulundensisencoding a sirtuin E with highest similarity to theA. nidulansprotein also activated theorsBGC in this fungus.
Elevated mutation rates in the multi-azole resistantAspergillus fumigatusclade drives rapid evolution of antifungal resistance
Authors: Bottery Michael J. , van Rhijn Norman , Chown Harry , Rhodes Johanna L. , Celia-Sanchez Brandi N. , Brewer Marin T. , Momany Michelle , Fisher Matthew C. , Knight Christopher G. , Bromley Michael J. 
Published: December 2023

AbstractThe evolution of antifungal resistance is an emerging global threat. Particularly concerning is the widespread occurrence of azole resistance withinAspergillus fumigatus, a globally ubiquitous environmental mould that causes over 1 million life-threatening invasive infections in humans each year. It is increasingly evident that the environmental use of azoles has led to selective sweeps across multiple genomic loci resulting in the rapid expansion of a genetically distinct cluster of genotypes (clade A) that results in resistance to clinically deployed azoles. Isolates within this cluster are more likely to be cross resistant to agricultural antifungals with unrelated modes of action suggesting they may be adapting rapidly to antifungal challenge. Here we show that this cluster is not only multi-azole resistant but has increased propensity to develop resistance to new antifungals because of variants in the DNA mismatch repair system. A variant inmsh6is found almost exclusively within clade A, occurs in 88% of multi-azole resistant isolates harbouring the canonicalcyp51Aazole resistance allelic variant TR34/L98H, and is globally distributed. Naturally occurring isolates with thismsh6variant display a 4 to 9-times higher rate of mutation, leading to an increased propensity to evolve resistance to current and next generation antifungals. We argue that pervasive environmental use of fungicides creates selective arenas whereby genotypes ofA. fumigatuswith increased adaptive capability thrive in the face of strong directional selection, leading to the genesis and amplification of antifungal resistance. These results help explain the pronounced clustering of multiple independent resistance mechanisms within the mutable clade A. Our findings further suggest that resistance to next generation antifungals is more likely to emerge within organisms that are already multi-azole resistant, posing a major problem due to the prospect of dual use of novel antifungals in clinical and agricultural settings.
An improved chromosome-level genome assembly of perennial ryegrass (Lolium perenneL.)
Authors: Chen Yutang , Kölliker Roland , Mascher Martin , Copetti Dario , Himmelbach Axel , Stein Nils , Studer Bruno 
Published: December 2023

ABSTRACTThis work is an update and extension of the previously published article “Ultralong Oxford Nanopore Reads Enable the Development of a Reference-Grade Perennial Ryegrass Genome Assembly”, by Frei et al.. The published genome assembly of the doubled haploid perennial ryegrass (Lolium perenneL.) genotype Kyuss marked a milestone for forage grass research and breeding. However, order and orientation errors may exist in the pseudo-chromosomes of Kyuss, since barley (Hordeum vulgareL.), which diverged 30 million years ago from perennial ryegrass, was used as the reference to scaffold Kyuss. To correct for structural errors possibly present in the published Kyuss assembly, wede novoassembled the genome again and generated 50-fold coverage high-throughput chromosome conformation capture (Hi-C) data to assist pseudo-chromosome construction. The resulting new chromosome-level assembly showed improved quality with high contiguity (contig N50 = 120 Mb), high completeness (total BUSCO score = 99%), high base-level accuracy (QV = 50) and correct pseudo-chromosome structure (validated by Hi-C contact map). This new assembly will serve as a better reference genome forLoliumspp. and greatly benefit the forage and turf grass research community.
Segregation-to-Integration Transformation Model of Memory Evolution
Authors: Bavassi Luz , Fuentemilla Lluís 
Published: December 2023

AbstractMemories are thought to use coding schemes that dynamically adjust their representational structure to maximize both persistence and utility. However, the nature of these coding scheme adjustments and their impact on the temporal evolution of memory after initial encoding is unclear. Here we introduce the Segregation-to-Integration Transformation (SIT) Model, a neural network formalization that offers a unified account of how the representational structure of a memory is transformed over time. SIT Model asserts that memories initially adopt a highly modular or segregated network structure, functioning as an optimal storage buffer by striking a balance between protection from disruptions and accommodating substantial information. Over time, a repeated combination of neural network reactivations, spreading, and synaptic plasticity transforms the initial modular memory structure into an integrated memory form, facilitating intercommunity spreading and fostering generalization. In addition, SIT Model reveals the existence of an optimal window during this transformation where memories are most susceptible to malleability, suggesting a non-linear or inverted U-shaped function in memory evolution. The results of our model integrate a wide range of experimental phenomena along with accounts of memory consolidation and reconsolidation, offering a unique perspective on memory evolution by leveraging simple architectural neural network property rules.
Discovery of high affinity and specificity stapled peptide Bcl-xL inhibitors using bacterial surface display
Authors: Case Marshall , Vinh Jordan , Kopp Anna , Smith Matthew , Thurber Greg 
Published: December 2023

AbstractIntracellular protein-protein interactions are involved in many different diseases, making them prime targets for therapeutic intervention. Several diseases are characterized by their overexpression of Bcl-xL, an anti-apoptotic B cell lymphoma 2 (Bcl-2) protein expressed on mitochondrial membranes. Bcl-xLoverexpression inhibits apoptosis, and selective inhibition of Bcl-xLhas the potential to increase cancer cell death while leaving healthy cells comparatively less affected. However, high homology between Bcl-xLand other Bcl-2 proteins has made it difficult to selectively inhibit this interaction by small molecule drugs. We engineered stapled peptides, a chemical modification that can improve cell penetration, protease stability, and conformational stability, towards the selective inhibition of Bcl-xL. To accomplish this task, we built a focused combinatorial mutagenesis library of peptide variants on the bacterial cell surface, used copper catalyzed click chemistry to form stapled peptides, and sorted the library for high binding to Bcl-xLand minimal binding towards other Bcl-2 proteins. We characterized the sequence and staple placement trends that governed specificity and identified molecules with ∼10 nM affinity to Bcl-xLand greater than 100-fold selectivity versus other Bcl-2 family members on and off the cell surface. We confirmed the mechanism of action of these peptides is consistent with apoptosis biology through mitochondrial outer membrane depolarization assays (MOMP). Overall, high affinity (10 nM Kd) and high specificity (100-fold selectivity) peptides were developed to target the Bcl-xLprotein. These results demonstrate that stapled alpha helical peptides are promising candidates for the specific treatment of cancers driven by Bcl-2 dysregulation.
Noncoding function of super enhancer derived mRNA in modulating neighboring gene expression and TAD interaction
Authors: Xie Bingning , Dean Ann 
Published: December 2023

ABSTRACTSuper enhancers are important regulators of gene expression that often overlap with protein-coding genes. However, it is unclear whether the overlapping protein-coding genes and the mRNA derived from them contribute to enhancer activity. Using an erythroid-specific super enhancer that overlaps theCpoxgene as a model, we found thatCpoxmRNA has a non-coding function in regulating neighboring protein-coding genes, eRNA expression and TAD interactions. Depletion ofCpoxmRNA leads to accumulation of H3K27me3 and release of p300 from theCpoxlocus, activating an intra-TAD enhancer and gene expression. Additionally, we identified a head-to-tail interaction between the TAD boundary genesCpoxandDcbld2that is facilitated by a novel type of repressive loop anchored by p300 and PRC2/H3K27me3. Our results uncover a regulatory role for mRNA transcribed within a super enhancer context and provide insight into head-to-tail inter-gene interaction in the regulation of gene expression and oncogene activation.
Ligand Response of Guanidine-IV riboswitch at Single-molecule Level
Authors: Gao Lingzhi , Chen Dian , Liu Yu 
Published: December 2023

ABSTRACTRiboswitches represent a class of non-coding RNA that possess the unique ability to specifically bind ligands and, in response, regulate gene expression. A recent report unveiled a type of riboswitch, known as the guanidine-IV riboswitch, which responds to guanidine levels to regulate downstream genetic transcription. However, the precise molecular mechanism through which the riboswitch senses its target ligand and undergoes conformational changes remain elusive. This gap in understanding has impeded the potential applications of this riboswitch. To bridge this knowledge gap, our study investigated the conformational dynamics of the guanidine-IV riboswitch RNA upon ligand binding. We employed single-molecule fluorescence resonance energy transfer (smFRET) to dissect the behaviors of the aptamer, terminator, and full-length riboswitch. Our findings indicated that the aptamer portion exhibited higher sensitivity to guanidine compared to the terminator and full-length constructs. Additionally, we utilized Position-specific Labelling of RNA (PLOR) combined with smFRET to observe, at the single-nucleotide and single-molecule level, the structural transitions experienced by the guanidine-IV riboswitch during transcription. Notably, we discovered that the influence of guanidine on the riboswitch RNA’s conformations was significantly reduced after the transcription of 88 nucleotides. Furthermore, we proposed a folding model for the guanidine-IV riboswitch in the absence and presence of guanidine, thereby providing insights into its ligand-response mechanism.Impact statementThe aptamer domain of the guanidine-IV riboswitch exhibits a greater sensitivity to guanidine, surpassing that observed in both the terminator and full-length riboswitch. A finely-tuned transcriptional window of the guanidine-IV riboswitch was detected to be responsive to ligand binding. Furthermore, a folding-function model for the guanidine-IV riboswitch under both guanidine-free and guanidine-present conditions offers valuable insights into its regulatory mechanism.
A genome-wide survey of DNA methylation inPanax notoginsengreveals CHH hyper-methylation regulates the after-ripening and dormancy of recalcitrant seeds
Authors: Ge Na , Jia Jin-Shan , Wang Qing-Yan , Li Chao-Lin , Huang Min , Chen Jun-Wen 
Published: December 2023

AbstractDNA methylation plays a crucial role in regulating fruit ripening and seed development. It remains unknown about the dynamic characteristics of DNA methylation and its regulation mechanisms in morpho-physiological dormancy (MPD)-typed seeds with recalcitrant characteristics. TheP. notoginsengseeds are defined by the MPD and are characterized by a strong sensitivity to dehydration during the after-ripening process. We performed DNA methylomes, siRNA profiles, and transcriptomes of embryo and endosperm inP. notoginsengseeds at different after-ripening stages. Herein, we find that the CHH hyper-methylation contributes to the global increase in DNA methylation during the after-ripening process ofP. notoginsengseeds. The endosperm genome is hyper-methylated compared to the embryo genome. The CHH hyper-methylation is caused by the high expression level of DNA methyltransferasePnCMT2in the embryo, andPnDRM2in the endosperm, respectively. The CHH hyper-methylation alters gene transcription levels to regulate the after-ripening and dormancy of recalcitrant seeds. For example, it inhibits the expression of genes in embryo development to make seeds maintain a dormant status, whereas it activates the expression of genes in the hormone-mediated signaling pathway, and energy metabolism to accomplish the MPD-typed seed after-ripening process. Together, our findings reveal a global increase in DNA methylation and its vital driver in gene expression, and thus elucidate how global CHH hyper-methylation regulates the after-ripening in recalcitrant MPD-typed seeds. This work establishes a key role for epigenetics in regulating the dormancy of MPD-typed seeds with recalcitrant characteristics.
Mr. Smith goes to flatland: institutions, public policy and the bossless company
Authors: McCaffrey Matthew 
Published: December 2023

PurposeThis study aims to explore a range of institutional, environmental and policy conditions that influence the creation of “bossless” or “flat” companies, i.e. firms with little or no formal hierarchy.Design/methodology/approachThe author builds on the theory and evidence presented by Foss and Klein (2022) in their study of the costs and benefits of organizing without hierarchy. The author also draws on a variety of related theoretical insights and empirical evidence. The paper is exploratory and anecdotal though and is intended to motivate further research rather than provide a definitive account of bossless organizing.FindingsThe paper develops nine propositions. It suggests that high levels of economic freedom create maximum scope for entrepreneurs to experiment with different organizational forms (1). Likewise, a lack of economic freedom increases the scope for the government to experiment (2). Markets characterized by technological innovation and uncertainty are likely to discourage bossless organizing (3 and 4), while stagnating industries with major capital requirements are likely to encourage it (5). Labor market interventions that increase the cost of employment contracts sometimes encourage firms to flatten (6), but more generally, these interventions encourage expanding management layers (7). In environments with strong intellectual property (IP) laws, companies with more modular and knowledge-based work are more likely to flatten (8). The creation of low-hierarchy firms such as cooperatives is encouraged by public subsidies, access to cheap credit and preferential tax treatment (9).Originality/valueStudies of bossless or flat firms focus almost exclusively on describing their internal organization and evaluating their performance; little attention is paid to the conditions that encourage or discourage the emergence of these firms. This paper focuses on the latter, with a view to encouraging more scholarly interest in this field.
Effect of board structure on stakeholders’ centric perspective of sustainable corporate world
Authors: Bhat Basit Ali , Makkar Manpreet Kaur , Gupta Nitin 
Published: December 2023

Purpose
Corporate leadership and environmental, social and governance (ESG) performance are closely intertwined, as effective corporate leadership can facilitate the achievement of strong ESG performance. Thus, the purpose of the study is to investigate the impact of corporate board leadership on the ESG performance of listed firms.

Design/methodology/approach
The sample has been taken from the listed firms of the Nifty 500 index spanning the period of 10 years from 2012 to 2022. Dynamic panel data estimations are applied through a fixed effect model.

Findings
The findings of this study revealed that board size, board independence and board qualification have a significant positive influence on ESG performance. It is evident that good corporate governance practices can positively influence ESG performance by fostering accountability, transparency and ethical behavior, as well as better integrating ESG considerations into their decision-making processes and ensuring that ESG issues are prioritized at the highest levels of management. Further findings also revealed that chief executive officer (CEO) duality has a significant negative relationship with ESG performance, which goes against the belief of stakeholder theory.

Social implications
It has practical implications for policymakers, as they can enact new regulations pertaining to the CEO’s position in the organizations to make corporate governance responsible for improved sustainability and ESG performance.

Originality/value
There are very few studies analyzing the impact of corporate board structure on ESG performance related to emerging markets. Thus, this study contributes to that literature by using the methodology GMM panel data for the first time as per our knowledge
Exploring the role of organizational developmental HR practices in enhancing employees' commitment to organizational career: a multilevel investigation
Authors: Deng Ting , Tang Chunyong , Lai Yanzhao 
Published: December 2023

PurposeDrawing upon the conservation of resources (COR) theory, this study examined the relationship between organizational developmental human resource (HR) practices and employees' commitment to the organizational career (COC), while considering the mediating role of psychological availability and the moderating effects of links and fit.Design/methodology/approachA hierarchical linear modeling analysis was conducted to analyze the data from a 3-wave time-lagged study with 394 employees and 65 supervisors in ten Chinese firms.FindingsThe study's findings suggest that organizational developmental HR practices have a positive and indirect impact on employees' COC, with psychological availability serving as a mediator. The indirect effects were stronger for employees with stronger links and better fit.Practical implicationsThis study provides managers with guidelines to improve employees' COC. Managers should also focus on supporting employees' psychological resources. Furthermore, organizations should be aware that employees with varying levels of links and fit may respond differently to psychological availability.Originality/valueThe study offers a new understanding of how and under what conditions organizational developmental HR practices can increase employees' COC. It also highlights the role of psychological availability as the psychological mechanism mediating this relationship and adds to the limited literature on the potential positive impact of strong links and fit.
Modeling corporate social responsibility and organizational attractiveness: the underlying mechanism of organizational trust
Authors: Chowdhury Md Sohel , Moniruzzaman H.M. , Lipy Nusrat Sharmin , Kang Dae-seok 
Published: December 2023

PurposeDrawing on signaling and social identity theories, the main objective of this paper is to suggest and validate a research framework to investigate the association of corporate social responsibility (CSR) perceptions with organizational attractiveness by uncovering the underlying mechanism of organizational trust.Design/methodology/approachBy conducting regression analysis, the study hypotheses were tested with the data collected from a snowball convenient sample of 318 potential job seekers.FindingsThe study results revealed that prospective applicants' perceptions about a company's CSR undertakings are significantly associated with their trust in and attraction to the company. Noticeably, organizational trust partially mediated the direct relationship between CSR perceptions and organizational attractiveness.Research limitations/implicationsBased on the study results, some specific theoretical advancements and helpful insights have been highlighted for human resources (HR) practitioners in today's competing organizations. The paper ends by outlining key research drawbacks and directions for possible work in the future.Originality/valueDespite the plausible underlying role of organizational trust in the link between CSR and organizational attraction, empirical studies of this theoretical phenomenon are still lacking in the context of pre-hire recruitment literature. This may be the first study that identifies organizational trust as a salient psychological factor through which job seekers' CSR perceptions become more instrumental in influencing their attraction to a firm.