bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional screening identifies novel miRNAs inhibiting Vascular Smooth Muscle Cell proliferation
Authors: Rodor Julie , Klimi Eftychia , Braga Luca , Ring Nadja A.R. , Ballantyne Margaret D. , Miscianinov Vladislav , Vacante Francesca , Miteva Katarina , Kesidou Despoina , Bennett Matthew , Beqqali Abdelaziz , Giacca Mauro , Zacchigna Serena , Baker Andrew H. 
Published: April 2024

ABSTRACTProliferation of vascular smooth muscle cells (vSMCs) following injury is a crucial contributor to pathological vascular remodelling. MicroRNAs (miRNAs) are powerful gene regulators and attractive therapeutic agents. Here, we aim to systematically identify and characterise miRNAs with therapeutic potential in targeting aberrant vSMC proliferation. We performed a high-throughputin vitroscreen using a library of 2042 human miRNA-mimics for their impact on vSMC proliferation and identified seven novel antiproliferative miRNAs i.e miR-323a-3p, miR449b-5p, miR-491-3p, miR-892b, miR-1827, miR-4774-3p, miR-5681b. Overexpression of these seven miRNAs affects proliferation of vSMCs from different vascular beds. Focusing on vein graft failure, a condition in which miRNA-based therapeutics can be applied to the graft ex-vivo, we showed that these miRNAs reduced human saphenous vein SMC (HSVSMC) proliferation without inducing apoptosis or senescence, and five of them also significantly decreased migration. HSVSMC transcriptomic analysis showed that each miRNA overexpression affects a core cell cycle gene network. However, this effect is mediated by distinct miRNA targets. In contrast to HSVSMC, miRNA overexpression in saphenous vein endothelial cells (ECs) led to no decrease or a less pronounced reduction in proliferation for the seven miRNAs. Transcriptomics analysis confirmed a distinct and limited response of ECs to the miRNA overexpression.
New gamma interferon (IFN-γ) algorithm for tuberculosis diagnosis in cynomolgus macaques
Authors: Warit Saradee , Meesawat Suthirote , Cheawchanlertfa Pattsarun , Makhoa Nampueng , Srilohasin Prapaporn , Kaewparuehaschai Machamon , Noradechanon Kirana , Pomcoke Areeya , Kemthong Taratorn , Prammananan Therdsak , Kanitpun Reka , Palaga Tanapat , Malaivijitnond Suchinda , Chaiprasert Angkana 
Published: April 2024

AbstractTuberculosis (TB) is the first infectious disease to be screened-out from specified pathogen-free cynomolgus macaques (Macaca fascicularis; Mf) using in human pharmaceutical testing. Being either latent or active stage after exposure to theMycobacterium tuberculosiscomplex (MTBC), the monkey gamma-interferon release assay (mIGRA) was previously introduced for early TB detection in Mf. However, a high number of indeterminate cases were unexpectedly encountered. The main reasons were a mitogen positive control and an interpretation algorithm. A cohort of 316 Mf exposed to MTBC was tested of two positive mitogen controls [QFT-PHA and a mixture of ConcanavalinA and Pokeweed (ConA+PWM)], and 100 of 316 animals were selected and 26-month followed-up for the establishment of a new mIGRA algorithm for interpretation. As such, the number of indeterminate cases was drastically reduced (80-100%) when the ConA + PWM mixture was used as a positive mitogen control along with a new mIGRA algorithm for interpretation.
Life with only 28 tRNAs: Reduced translation accuracy compensates for the lack of twelve tRNAs inSalmonella enterica
Authors: Näsvall Joakim 
Published: April 2024

AbstractDespite the link between codon usage bias and the composition of the tRNA pool, the evolutionary forces shaping codon usage and tRNA pools remain largely untested by experiment. This study investigates the relationship between tRNA pool composition and synonymous codon usage (SCU) by deleting twelve nonessential tRNAs inSalmonella enterica, generating an organism (ΔT12) with 28 essential tRNAs left, and a severe imbalance between its tRNA pool and SCU. Mutations selected during the construction of ΔT12 and in subsequent evolution experiments, suggest two key mechanisms for compensating the fitness effects of this imbalance: (i) Near-cognate tRNA adaptation: mutations or gene copy number variations allowed remaining tRNAs to better read codons originally assigned to missing tRNAs. (ii) Reduced translation accuracy: mutations in ribosomal proteins (S3, S4, S5, L7/L12) and EF-Tu likely increased the rate of near-cognate decoding, prioritizing translation speed over accuracy. These findings suggest that translation rate may be a stronger evolutionary pressure than maintaining perfect accuracy when there is a mismatch between the tRNA pool and SCU. The ΔT12 strain provides a valuable tool for further exploring the co-evolution of the tRNA pool and SCU.
Modulation of input to the spinal cord; contribution of GABA released by interneurons and glial cells by polarization at the entry of sensory information
Authors: Hammar Ingela , Jankowska Elzbieta 
Published: April 2024

ABSTRACTModulation of input from primary afferent fibres has long been examined at the level of the first relay neurons of these fibres. However, recent studies reveal that input to the spinal cord may also be modulated before action potentials in intraspinal collaterals of afferent fibres reach their target neurons, even at the level of the very entry of afferent fibres to the spinal grey matter. Such modulation greatly depends on the actions of GABA via extrasynaptic membrane receptors. In the reported study we hypothesized that the increase in excitability of afferent fibres following epidural polarization close to the site where collaterals of afferent fibres leave the dorsal columns is due to the release of GABA from two sources: not only terminals of GABAergic interneurons but also glial cells. We present evidence, primo, that GABA from both these sources contributes to a long-lasting increase in the excitability and a shortening of the refractory period of epidurally stimulated afferents fibres and, secondo, that effects of epidural polarization on GABA-containing terminals of GABAergic interneurons and on glial cells are more critical for these changes than direct effects on the stimulated fibres. The experiments were carried out in deeply anaesthetized rats in which changes in compound action potentials evoked in hindlimb peripheral nerves by dorsal column stimulation were used as a measure of the excitability of afferent fibres. The study throws new light on the modulation of input to spinal networks but also on mechanisms underlying the restoration of spinal functions.
The effect of a short oxygen exposure period on algal biomass degradation and methane formation in eutrophic and oligotrophic lake sediments
Authors: van Grinsven Sigrid , Maeda Natsumi , Glombitza Clemens , Lever Mark A. , Schubert Carsten J. 
Published: April 2024

AbstractEutrophication is suggested to enhance lacustrine methane emissions, due to enhanced sedimentary decomposition rates of algal biomass, and more frequent occurrence of water column anoxia. We investigated methane emissions from sediments originating from both a eutrophic and oligotrophic lake, and tested the effect of additional algal C inputs. Additionally, we investigated the effect of a pulse supply of oxygen, a mediating measure that is currently being used in the investigated eutrophic lake. Our results show a large legacy effect of eutrophication, but the methane release from new algal biomass additions was the same, although the process proceeded more rapidly in the eutrophic sediments. A short, 3-week pulse of oxygen lowered the emitted methane from both types of sediments by 50%, not only reducing the emissions of algal biomass additions, but also reducing methane emissions from the experiments without fresh organic matter inputs. This effect was relatively long-lasting: its effects were visible for several weeks after anoxic conditions were re-established, making it a potentially interesting measure to lower methane emissions over a longer period. Volatile fatty acid concentrations in the sediments were lowered due to oxygen exposure. Both the methanogenic and methanotrophic community composition showed surprisingly little response to the oxygen or algal biomass pulses. Overall, our results show that providing sediments with a brief pulse of oxygen following an algal bloom event, could strongly mediate the methane emissions following such an event. Such measures could be considered by policy makers to limit greenhouse gas emissions from managed lakes.
European Farmhouse Brewing Yeasts Form a Distinct Genetic Group
Authors: Preiss Richard , Fletcher Eugene , Garshol Lars Marius , Foster Barret , Ozsahin Emine , Lubberts Mark , van der Merwe George , Krogerus Kristoffer 
Published: April 2024

AbstractThe brewing industry is constantly evolving, driven by the quest for novel flavors and fermentation characteristics that cater to evolving consumer preferences. This study explores the genetic and phenotypic diversity of European farmhouse yeasts, traditionally used in rural brewing practices and maintained outside of pure culture industrial yeast selection. We isolated landrace brewing yeast strains from diverse geographical locations across Europe, including Norway, Lithuania, Latvia, Russia, and also included African farmhouse brewing strains from Ghana. Our genomic analysis using long-read and short-read whole genome sequencing uncovered a genetically distinct group that diverges from industrial brewing yeasts. This group, which is closely related to ale brewing strains, is preliminarily named the “European Farmhouse” group and shows greater predicted admixture from Asian fermentation strains. Through genomic and phenotypic analyses, including flavor metabolite analysis via HS-GC-MS, sugar metabolite analysis via HPLC, and wort fermentation analysis, we found a broad spectrum of fermentation capabilities, from rapid and efficient fermentation to unique aroma and flavor compound profiles, potentially offering novel traits for brewing applications. This study highlights the importance of preservation of brewing cultural heritage knowledge and resources including yeast cultures.Key PointsA large set of geographically diverse farmhouse brewing strains were characterizedNorwegian and Baltic farmhouse brewing strains form a distinct genetic groupFarmhouse strains show considerable diversity in fermentation and flavour formation
Biosynthesis of oxyresveratrol in mulberry (Morus albaL.) is mediated by a group of p-coumaroyl-CoA 2’-hydroxylases acting upstream of stilbene synthases
Authors: Santiago Antonio , Romero Pablo , Martínez Ascensión , Martínez María José , Echeverría Jone , Selles Susana , Alvarez-Urdiola Raquel , Zhang Chen , Navarro-Payá David , Pizzio Gastón A. , Micó Estel·la , Samper Antonio , Morante Jaime , Cigliano Riccardo Aiese , Manzano David , Bru Roque , Matus José Tomás 
Published: April 2024

AbstractMulberry (Morus albaL.) is considered a millenary medicinal plant and a food source for silkworms. DifferentM. albaextracts offer a variety of biological and pharmacological properties that are in part attributed to stilbenoids, a small group of phenylpropanoids that include resveratrol and oxyresveratrol. These are naturally present in non-renewable parts of mulberry trees, impeding their efficient extraction. As a way to bypass this spatiotemporal restriction, we generated cell suspensions from mulberry twigs and demonstrated that the combined use of methyl jasmonate and methyl- or hydroxypropyl-β-cyclodextrins elicited a high production of resveratrol and oxyresveratrol, both intra and extracellularly. To identify oxyresveratrol-producing enzymes (unknown to date), we first improved the structural and functional annotation of the mulberry genome by integrating short and long-read sequencing data. We further combined this data with transcriptome, metabolite and proteome time-series evidence to identify a complete set of elicited phenylpropanoid- and stilbenoid-related genes. These included 22 stilbene synthase (STS) genes and a group of sixp-coumaroyl-CoA 2’-hydroxylases (C2’Hs) that were highly co-expressed with resveratrol and oxyresveratrol accumulation. We transiently transformedNicotiana benthamianaplants and grapevine (Vitis viniferaL.) cell suspensions to functionally validate the role of C2’Hs as the first committed step of oxyresveratrol synthesis, providing an alternative substrate for STSs by hydroxylatingp-coumaroyl-coA into 2’4’-dihydroxycinnamoyl-CoA. We offer tools for genomic and transcriptomic exploration in the context of jasmonate elicitation aiding in the characterization of novel stilbenoid-modifying and regulatory genes in theMorusgenus.
Vibrio choleraepathogenicity island 2 encodes two distinct types of restriction systems
Authors: Vizzarro Grazia , Lemopoulos Alexandre , Adams David William , Blokesch Melanie 
Published: April 2024

AbstractIn response to predation by bacteriophages and invasion by other mobile genetic elements such as plasmids, bacteria have evolved specialised defence systems that are often clustered together on genomic islands. The O1 El Tor strains ofVibrio choleraeresponsible for the ongoing seventh cholera pandemic (7PET) contain a characteristic set of genomic islands involved in host colonisation and disease, many of which contain defence systems. Notably,Vibriopathogenicity island 2 contains several characterised defence systems as well as a putative Type I restriction-modification system (T1RM), which, interestingly, is interrupted by two genes of unknown function. Here, we demonstrate that the T1RM system is active, methylates the host genomes of a representative set of 7PET strains, and identify a specific recognition sequence that targets non-methylated plasmids for restriction. We go on to show that the two genes embedded within the T1RM system encode a novel two-protein modification-dependent restriction system related to the GmrSD family of Type IV restriction enzymes. Indeed, we show that this system has potent anti-phage activity against diverse members of theTevenvirinae, a subfamily of bacteriophages with hypermodified genomes. Taken together these results expand our understanding of how this highly conserved genomic island contributes to the defence of pandemicV. choleraeagainst foreign DNA.
LiaR-dependent gene expression contributes to antimicrobial responses in group AStreptococcus
Authors: Vega Luis Alberto , Sansón-Iglesias Misu , Mukherjee Piyali , Buchan Kyle , Morrison Gretchen , Hohlt Anne E. , Flores Anthony R. 
Published: April 2024

AbstractThe ability to sense and respond to host defenses is essential for pathogen survival. Some mechanisms involve two-component systems (TCS) that respond to host molecules, such as antimicrobial peptides (AMPs) and activate specific gene regulatory pathways to aid in survival. Alongside TCSs, bacteria coordinate cell division proteins, chaperones, cell wall sortases and secretory translocons at discrete locations within the cytoplasmic membrane, referred to as functional membrane microdomains (FMMs). In Group AStreptococcus(GAS), the FMM or “ExPortal” coordinates protein secretion, cell wall synthesis and sensing of AMP-mediated cell envelope stress via the LiaFSR three-component system. Previously we showed GAS exposure to a subset of AMPs (α-defensins) activates the LiaFSR system by disrupting LiaF and LiaS co-localization in the ExPortal, leading to increased LiaR phosphorylation, expression of the transcriptional regulator SpxA2, and altered GAS virulence gene expression. The mechanisms by which LiaFSR integrates cell envelope stress with responses to AMP activity and virulence are not fully elucidated. Here, we show the LiaFSR regulon is comprised of genes encoding SpxA2 and three membrane-associated proteins: a PspC domain-containing protein (PCP), the lipoteichoic acid-modifying protein LafB and the membrane protein insertase YidC2. Our data show phosphorylated LiaR induces transcription of these genes via a conserved operator, whose disruption attenuates GAS virulence and increases susceptibility to AMPs in a manner primarily dependent on differential expression of SpxA2. Our work expands understanding of the LiaFSR regulatory network in GAS and identifies targets for further investigation of mechanisms of cell envelope stress tolerance contributing to GAS pathogenesis.
Higgs portal interpretation of the Belle II
B+→K+νν
measurement
Authors: McKeen David , Ng John N. , Tuckler Douglas 
Published: April 2024

The Belle II experiment recently observed the decay B+→K+νν for the first time, with a measured value for the branching ratio of (2.3±0.7)×10−5. This result exhibits a ∼3σ deviation from the Standard Model (SM) prediction. The observed enhancement with respect to the Standard Model could indicate the presence of invisible light new physics. In this paper, we investigate whether this result can be accommodated in a minimal Higgs portal model, where the SM is extended by a singlet Higgs scalar that decays invisibly to dark sector states. We find that current and future bounds on invisible decays of the 125 GeV Higgs boson completely exclude a new scalar with a mass ≳10  GeV. On the other hand, the Belle II results can be successfully accommodated if the new scalar is lighter than B mesons but heavier than kaons. We also investigate the cosmological implications of the new states and explore the possibility that they are part of an Abelian Higgs extension of the SM. Future Higgs factories are expected to place stringent bounds on the invisible branching ratio of the 125 GeV Higgs boson, and will be able to definitively test the region of parameter space favored by the Belle II results.

Published by the American Physical Society
2024
Light mass window of inert doublet dark matter with lepton portal interaction
Authors: Higuchi Ryo , Iguro Syuhei , Okawa Shohei , Omura Yuji 
Published: April 2024

We study phenomenology of a light scalar dark matter (DM). In the model, there is an inert doublet scalar and a singlet Dirac fermion ψ, both charged under a global Z2 symmetry. The mass of the lightest inert scalar H can be lighter than 10 GeV by imposing appropriate relations between three scalar quartic couplings. The lightest Z2 odd particle is stable and DM. In this paper, focusing on the parameter space where H is lighter than ψ and is DM, we discuss DM physics related to relic density, direct detection, indirect detection, collider searches, and other cosmological observations. We clarify differences from the case where ψ is instead DM, which has been focused on in previous works.

Published by the American Physical Society
2024
How sustainability assurance work gets done: assurors’ sensemaking, socialization and interactions with clients
Authors: Bouten Lies , Hoozée Sophie 
Published: April 2024

PurposeThis study examines how assurors make sense of sustainability assurance (SA) work and how interactions with assurance team members and clients shape assurors’ sensemaking and their actual SA work.Design/methodology/approachTo obtain detailed accounts of how SA work occurs on the ground, this study explores three SA engagements by interviewing the main actors involved, both at the client firms and at their Big Four assurance providers.FindingsIndividual assurors’ (i.e. partners and other team members) sensemaking of SA work results in the crafting of their logics of action (LoAs), that is, their meanings about the objectives of SA work and how to conduct it. Without organizational socialization, team members may not arrive at shared meanings and deviate from the team-wide assurance approach. To fulfill their objectives for SA work, assurors may engage in socialization with clients or assume a temporary role. Yet, the role negotiations taking place in the shadows of the scope negotiations determine their default role during the engagement.Practical implicationsTwo options are available to help SA statement users gauge the relevance of SA work: either displaying the SA work performed or making it more uniform.Originality/valueThis study theoretically grounds how assurors make sense of SA work and documents how (the lack of) professional socialization, organizational socialization and socialization of frequent interaction partners at the client shape actual SA work. Thereby, it unravels the SA work concealed behind SA statements.
Employee perceptions of hotel CSR initiatives and job satisfaction: exploring organizational identification, psychological contract fulfillment and attachment styles
Authors: Dang Toan Thi Phuoc , Do Vinh Thi Thanh 
Published: April 2024

PurposeThis study offers an empirical framework for how hotel employees CSR perceptions affect their job satisfaction by incorporating the parallel mediating roles of organizational identification and psychological contract fulfillment. In addition, it examines the moderator effects of employees' CSR-induced attributions on the constructed mediated model, providing a powerful lens through which to evaluate when and how employees' CSR perceptions influence organizational identification and psychological contract fulfillment.Design/methodology/approachThe study use PLS-SEM techniques to analyze a sample of 520 employees from 49 luxury hotels with 4–5 stars in Khanh Hoa province, Vietnam.FindingsThe results show that CSR positively influences job satisfaction through the mediating role of psychological contract fulfillment and organizational identification. Besides, attachment styles also play moderator role in the relationship between CSR and psychological contract fulfillment/organizational identification.Practical implicationsThe discoveries elucidated within this research endeavor proffer actionable discernments to be earnestly contemplated by professionals entrenched in the hotel industry, earnestly aspiring to ameliorate the contentment of their workforce and, concomitantly, augment the overarching efficacy of their organizational operations.Originality/valueThis study provides human resource departments with insights and suggestions for maximizing the efficacy of CSR implementation in the hotel industry.
Towards the environment of legitimacy: Do the institutional quality and policy uncertainty matter for the performance of stock markets of South Asian countries?
Authors: Khan Ather Azim , Ramzan Muhammad , Mehmood Shafaqat , Wong Wing-Keung 
Published: April 2024

PurposeThis paper assesses the environment of legitimacy by determining the role of institutional quality and policy uncertainty on the performance of five major South Asian stock markets (India, Pakistan, Bangladesh, Sri Lanka, and Nepal) using 21 years data from 2000 to 2020. The focus of this study is to approach the issue of the environment of legitimacy that leads to sustained market returns.Design/methodology/approachPanel cointegration tests of Kao and Pedroni are applied, and the Dynamic Panel Vector Autoregressive (PVAR) model is used to determine the estimates.FindingsADF P-Values of both Kao and Pedroni tests show that the panels are cointegrated; the statistical significance of the results of the Kao and Pedroni panel cointegration test confirms cointegration among the variables. After determining the most appropriate lag, the analysis is done using PVAR. The results indicate that institutional quality, policy uncertainty, and GDP positively affect stock market return. Meanwhile, government actions and inflation negatively affect stock market returns. On the other hand, stock market return positively affects institutional quality, government action, policy uncertainty, and GDP. While stock market return negatively affects inflation.Research limitations/implicationsThe sample is taken only from a limited number of South Asian countries, and the period is also limited to 21 years.Practical implicationsBased on our research findings, we have identified several policy implications recommended to enhance and sustain the performance of stock markets.Originality/valueThis paper uses a unique analytical tool, which gives a better insight into the problem. The value of this work lies in its findings, which also have practical implications and theoretical significance.