BMJ Ment Health. 2024 Dec 22;27(1):e301333. doi: 10.1136/bmjment-2024-301333.

ABSTRACT

Data sharing is a cornerstone of modern scientific research, playing a critical role in fostering greater collaboration, enhancing reproducibility, transparency and efficiency of scientific discoveries, and integrating diverse data sources. In circadian rhythm research, data sharing is particularly important due to the complexity and heterogeneity of the data, which includes molecular profiles, physiological measurements, clinical data and sensor-based data. UK research funders, such as Medical Research Council, Wellcome Trust and UK Research and Innovation, have established data-sharing policies to promote open science and enhance research transparency. Despite these policies, a recent assessment within the UK Circadian Mental Health Network (CMHN), which incorporates an analysis of publications from several countries, revealed that data sharing remains limited. Significant challenges including data complexity, privacy and ethical considerations, technical issues and entrenched academic culture are major barriers to progress. This perspective article highlights the current state of data sharing in circadian and mental health research, identifies key obstacles and compares these practices with broader trends. We also provide insights from principal investigators within the CMHN on the reasons for limited data sharing. To address these challenges, researchers can foster a culture of openness by seeking training, planning ahead in ethics processes and data management plans and using data outputs in research assessment. We outline CMHN's future plans to deliver training on Findable, Accessible, Interoperable, Reusable principles, offer data curation services and provide ethical guidelines. By adopting these strategies, we aim to improve data-sharing practices, ultimately advancing our understanding of circadian rhythms and their implications for mental health.

PMID:39715637 | DOI:10.1136/bmjment-2024-301333

J Nat Prod. 2024 Dec 23. doi: 10.1021/acs.jnatprod.4c01128. Online ahead of print.

ABSTRACT

Nonenzymatic reactions, though critical in natural product biosynthesis, are significantly challenging to control. Adding 3% NaI to the culture medium of Penicillium janczewskii significantly increased pseurotin D (1) production and decreased pseurotin A (2) production. Previously, 1 and 2 were suggested to be produced via a nonenzymatic reaction, where the epoxide at C-10 undergoes SN2 (2) or SN2' (1) reactions. We confirmed that 1 was isolated as a 1:1 mixture of C-13 epimers by spectral elucidation via CP3 analysis aided by selective excitation NMR methods, which supported that 1 was produced through a nonenzymatic SN2' reaction. We propose that NaI increased the ratio of 1 by causing steric hindrance at the C-11 position of the transient intermediate, which makes C-13 more preferred in the SN2/SN2' competition.

PMID:39714233 | DOI:10.1021/acs.jnatprod.4c01128

ISME J. 2024 Dec 23:wrae257. doi: 10.1093/ismejo/wrae257. Online ahead of print.

ABSTRACT

Most of the microbes in nature infrequently receive nutrients and are thus in slow- or non-growing states. How quickly they can resume their growth upon an influx of new resources is crucial to occupy environmental niches. Isogenic microbial populations are known to harbor only a fraction of cells with rapid growth resumption, yet little is known about the physiological characteristics of those cells and their emergence in the population. Here, we tracked growth of individual Escherichia coli cells in populations under fluctuating nutrient conditions. We found that shifting from high- to low-nutrient conditions caused stalling of cell growth with few cells continuing to divide extremely slowly, a process which was dependent on lipid turnover. Resuming high-nutrient inflow after low-nutrient conditions resulted in cells resuming growth and division, but with different lag times and leading to varying progeny. The history of cell growth during low-nutrient but not high-nutrient conditions was determinant for resumption of growth, which cellular genealogy analysis suggested to originate from inherited physiological differences. Our results demonstrate that cellular growth dynamics become diverse by nutrient limitations, under which a fraction of cells experienced a particular growth history can reproduce progeny with new resources in the future.

PMID:39714219 | DOI:10.1093/ismejo/wrae257

mSystems. 2024 Dec 26:e0131524. doi: 10.1128/msystems.01315-24. Online ahead of print.

ABSTRACT

The composition of bacterial transcriptomes is determined by the transcriptional regulatory network (TRN). The TRN regulates the transition from one physiological state to another. Here, we use independent component analysis to monitor the composition of the transcriptome during the transition from the exponential growth phase to the stationary phase. With Escherichia coli K-12 MG1655 as a model strain, we trigger the transition using carbon, nitrogen, and sulfur starvation. We find that (i) the transition to the stationary phase accompanies common transcriptome changes, including increased stringent responses and reduced production of cellular building blocks and energy regardless of the limiting element; (ii) condition-specific changes are strongly associated with transcriptional regulators (e.g., Crp, NtrC, CysB, Cbl) responsible for metabolizing the limiting element; and (iii) the shortage of each limiting element differentially affects the production of amino acids and extracellular polymers. This study demonstrates how the combination of genome-scale datasets and new data analytics reveals the fundamental characteristics of a key transition in the life cycle of bacteria.

IMPORTANCE: Nutrient limitations are critical environmental perturbations in bacterial physiology. Despite its importance, a detailed understanding of how bacterial transcriptomes are adjusted has been limited. By utilizing independent component analysis (ICA) to decompose transcriptome data, this study reveals key regulatory events that enable bacteria to adapt to nutrient limitations. The findings not only highlight common responses, such as the stringent response, but also condition-specific regulatory shifts associated with carbon, nitrogen, and sulfur starvation. The insights gained from this work advance our knowledge of bacterial physiology, gene regulation, and metabolic adaptation.

PMID:39714213 | DOI:10.1128/msystems.01315-24

J Integr Plant Biol. 2024 Dec 23. doi: 10.1111/jipb.13817. Online ahead of print.

ABSTRACT

Stomata are epidermal pores that are essential for water evaporation and gas exchange in plants. Stomatal development is orchestrated by intrinsic developmental programs, hormonal controls, and environmental cues. The steroid hormone brassinosteroid (BR) inhibits stomatal lineage progression by regulating BIN2 and BSL proteins in leaves. Notably, BR is known to promote stomatal development in hypocotyls as opposed to leaves; however, its molecular mechanism remains elusive. Here, we show that BR signaling has a dual regulatory role in controlling stomatal development in Arabidopsis hypocotyls. We found that brassinolide (BL; the most active BR) regulates stomatal development differently in a concentration-dependent manner. At low and moderate concentrations, BL promoted stomatal formation by upregulating the expression of SPEECHLESS (SPCH) and its target genes independently of BIN2 regulation. In contrast, high concentrations of BL and bikinin, which is a specific inhibitor of BIN2 and its homologs, significantly reduced stomatal formation. Genetic analyses revealed that BIN2 regulates stomatal development in hypocotyls through molecular mechanisms distinct from the regulatory mechanism of the cotyledons. In hypocotyls, BIN2 promoted stomatal development by inactivating BZR1, which suppresses the expression of SPCH and its target genes. Taken together, our results suggest that BR precisely coordinates the stomatal development of hypocotyls using an antagonistic control of SPCH expression via BZR1-dependent and BZR1-independent transcriptional regulation.

PMID:39714086 | DOI:10.1111/jipb.13817

Evolution. 2024 Dec 23:qpae187. doi: 10.1093/evolut/qpae187. Online ahead of print.

ABSTRACT

Facultatively parthenogenetic animals could help reveal the role of sexual conflict in the evolution of sex. Although each female can reproduce both sexually (producing sons and daughters from fertilized eggs) and asexually (typically producing only daughters from unfertilized eggs), these animals often form distinct sexual and asexual populations. We hypothesized that asexual populations are maintained through female resistance as well as the decay of male traits. We tested this via experimental crosses between individuals descended from multiple natural sexual and asexual populations of the facultatively parthenogenic stick-insect Megacrania batesii. We found that male-paired females descended from asexual populations produced strongly female-biased offspring sex-ratios resulting from reduced fertilization rates. This effect was not driven by incompatibility between diverged genotypes but, rather, by both genotypic and maternal effects on fertilization rate. Furthermore, when females from asexual populations mated and produced sons, those sons had poor fertilization success when paired with resistant females, consistent with male trait decay. Our results suggest that resistance to fertilization resulting from both maternal and genotypic effects, along with male sexual trait decay, can hinder the invasion of asexual populations by males. Sexual conflict could thus play a role in the establishment and maintenance of asexual populations.

PMID:39713880 | DOI:10.1093/evolut/qpae187

ACS Nanosci Au. 2024 Nov 15;4(6):416-425. doi: 10.1021/acsnanoscienceau.4c00040. eCollection 2024 Dec 18.

ABSTRACT

RNA-based agents (siRNA, miRNA, and mRNA) can selectively manipulate gene expression/proteins and are set to revolutionize a variety of disease treatments. Nanoparticle (NP) platforms have been developed to deliver functional mRNA or siRNA inside cells to overcome their inherent limitations. Recent studies have focused on siRNA to knock down proteins causing drug resistance or mRNA technology to introduce tumor suppressors. However, cancer needs multitargeted approaches to selectively manipulate multiple gene expressions/proteins. In this proof-of-concept study, we developed NPs containing Luc-mRNA and siRNA-GFP as model agents ((M+S)-NPs) and showed that NPs can simultaneously deliver functional mRNA and siRNA and impact the expression of two genes/proteins in vitro. Additionally, after in vivo administration, (M+S)-NPs successfully knocked down GFP while introducing luciferase into a TNBC mouse model, indicating that our NPs have the potential to develop RNA-based anticancer therapeutics. These studies pave the way to develop RNA-based, multitargeted approaches for complex diseases like cancer.

PMID:39713729 | PMC:PMC11659891 | DOI:10.1021/acsnanoscienceau.4c00040

Bioscience. 2024 Oct 14;74(12):825-839. doi: 10.1093/biosci/biae084. eCollection 2024 Dec.

ABSTRACT

In a hyperconnected world, framing and managing biological invasions poses complex and contentious challenges, affecting socioeconomic and environmental sectors. This complexity distinguishes the field and fuels polarized debates. In the present article, we synthesize four contentious issues in invasion science that are rarely addressed together: vocabulary usage, the potential benefits of nonnative species, perceptions shifting because of global change, and rewilding practices and biological invasions. Researchers have predominantly focused on single issues; few have addressed multiple components of the debate within or across disciplinary boundaries. Ignoring the interconnected nature of these issues risks overlooking crucial cross-links. We advocate for interdisciplinary approaches that better integrate social and natural sciences. Although they are challenging, interdisciplinary collaborations offer hope to overcome polarization issues in invasion science. These may bridge disagreements, facilitate knowledge exchange, and reshape invasion science narratives. Finally, we present a contemporary agenda to advance future research, management, and constructive dialogue.

PMID:39713562 | PMC:PMC11660934 | DOI:10.1093/biosci/biae084

ISME Commun. 2024 Dec 3;4(1):ycae151. doi: 10.1093/ismeco/ycae151. eCollection 2024 Jan.

ABSTRACT

Alga-dominated geothermal spring communities in Yellowstone National Park (YNP), USA, have been the focus of many studies, however, relatively little is known about the composition and community interactions which underpin these ecosystems. Our goal was to determine, in three neighboring yet distinct environments in Lemonade Creek, YNP, how cells cope with abiotic stressors over the diurnal cycle. All three environments are colonized by two photosynthetic lineages, Cyanidioschyzon and Galdieria, both of which are extremophilic Cyanidiophyceae red algae. Cyanidioschyzon, a highly specialized obligate photoautotroph, dominated cell counts at all three Lemonade Creek environments. The cell cycle of Cyanidioschyzon in YNP matched that observed in synchronized cultures, suggesting that light availability plays a strong role in constraining growth of this alga in its natural habitat. Surprisingly, the mixotrophic and physiologically more flexible Galdieria, was a minor component of these algal populations. Arsenic detoxification at Lemonade Creek occurred via complementary gene expression by different eukaryotic and prokaryotic lineages, consistent with this function being shared by the microbial community, rather than individual lineages completing the entire pathway. These results demonstrate the highly structured nature of these extreme habitats, particularly regarding arsenic detoxification.

PMID:39711979 | PMC:PMC11662350 | DOI:10.1093/ismeco/ycae151

Elife. 2024 Dec 23;13:RP93002. doi: 10.7554/eLife.93002.

ABSTRACT

Sudden death after myocardial infarction (MI) is associated with electrophysiological heterogeneities and ionic current remodelling. Low ejection fraction (EF) is used in risk stratification, but its mechanistic links with pro-arrhythmic heterogeneities are unknown. We aim to provide mechanistic explanations of clinical phenotypes in acute and chronic MI, from ionic current remodelling to ECG and EF, using human electromechanical modelling and simulation to augment experimental and clinical investigations. A human ventricular electromechanical modelling and simulation framework is constructed and validated with rich experimental and clinical datasets, incorporating varying degrees of ionic current remodelling as reported in literature. In acute MI, T-wave inversion and Brugada phenocopy were explained by conduction abnormality and local action potential prolongation in the border zone. In chronic MI, upright tall T-waves highlight large repolarisation dispersion between the border and remote zones, which promoted ectopic propagation at fast pacing. Post-MI EF at resting heart rate was not sensitive to the extent of repolarisation heterogeneity and the risk of repolarisation abnormalities at fast pacing. T-wave and QT abnormalities are better indicators of repolarisation heterogeneities than EF in post-MI.

PMID:39711335 | DOI:10.7554/eLife.93002

Physiol Plant. 2025 Jan-Feb;177(1):e70022. doi: 10.1111/ppl.70022.

ABSTRACT

Steryl esters (SE) are a storage pool of sterols that accumulates in cytoplasmic lipid droplets and helps to maintain plasma membrane sterol homeostasis throughout plant growth and development. Ester formation in plant SE is catalyzed by phospholipid:sterol acyltransferase (PSAT) and acyl-CoA:sterol acyltransferase (ASAT), which transfer long-chain fatty acid groups to free sterols from phospholipids and acyl-CoA, respectively. Comparative mass spectrometry-based metabolomic analysis between ripe fruits and seeds of a tomato (Solanum lycopersicum cv Micro-Tom) mutant lacking functional PSAT and ASAT enzymes (slasat1xslpsat1) shows that disruption of SE biosynthesis has a differential impact on the metabolome of these organs, including changes in the composition of free and glycosylated sterols. Significant perturbations were observed in the fruit lipidome in contrast to the mild effect detected in the lipidome of seeds. A contrasting response was also observed in phenylpropanoid metabolism, which is down-regulated in fruits and appears to be stimulated in seeds. Comparison of global metabolic changes using volcano plot analysis suggests that disruption of SE biosynthesis favours a general state of metabolic activation that is more evident in seeds than fruits. Interestingly, there is an induction of autophagy in both tissues, which may contribute along with other metabolic changes to the phenotypes of early seed germination and enhanced fruit tolerance to Botrytis cinerea displayed by the slasat1xslpsat1 mutant. The results of this study reveal unreported connections between SE metabolism and the metabolic status of plant cells and lay the basis for further studies aimed at elucidating the mechanisms underlying the observed effects.

PMID:39710490 | DOI:10.1111/ppl.70022

Food Chem. 2024 Dec 17;469:142547. doi: 10.1016/j.foodchem.2024.142547. Online ahead of print.

ABSTRACT

Roasting degrades the coffee compound mozambioside (1) into several products, including 17-O-β-D-glucosyl-11-hydroxycafestol-2-one (2), 11-O-β-D-glucosyl-16-desoxycafestol-2-one (3), 11-O-β-D-glucosyl-(S)-16-desoxy-17-oxocafestol-2-one (4), 11-O-β-D-glucosyl-15,16-dehydrocafestol-2-one (5), 11-O-β-D-glucosyl-(R)-16-desoxy-17-oxocafestol-2-one (6), bengalensol (7), and 11-hydroxycafestol-2-one (8). A UHPLC-MS/MS method was established to quantify 1-8 and monitor their formation during authentic coffee roasting. Concentrations of 1 and the dominant roasting products 4, 5, and 7 ranged from 21.0 to 170.4 nmol/g in coffee powders, with ∼41-128 % extracted into the brew. Human bitter taste thresholds of 1, 2, and 4-8 were determined. The major roasting products exhibited lower thresholds (27-80 μM) than 1 (132 μM). Genotyping of panelists revealed a correlation between sensitivity for mozambioside-derivatives and the presence of intact TAS2R43 gene loci. The combination of 1-8 in coffee concentrations elicited a bitter taste recognized in 80 % of the panelists, suggesting this compound class contributes to coffee's taste profile.

PMID:39709917 | DOI:10.1016/j.foodchem.2024.142547

Redox Biol. 2024 Dec 16;79:103464. doi: 10.1016/j.redox.2024.103464. Online ahead of print.

ABSTRACT

Non-communicable chronic diseases (NCDs) are most commonly characterized by age-related loss of homeostasis and/or by cumulative exposures to environmental factors, which lead to low-grade sustained generation of reactive oxygen species (ROS), chronic inflammation and metabolic imbalance. Nuclear factor erythroid 2-like 2 (NRF2) is a basic leucine-zipper transcription factor that regulates the cellular redox homeostasis. NRF2 controls the expression of more than 250 human genes that share in their regulatory regions a cis-acting enhancer termed the antioxidant response element (ARE). The products of these genes participate in numerous functions including biotransformation and redox homeostasis, lipid and iron metabolism, inflammation, proteostasis, as well as mitochondrial dynamics and energetics. Thus, it is possible that a single pharmacological NRF2 modulator might mitigate the effect of the main hallmarks of NCDs, including oxidative, proteostatic, inflammatory and/or metabolic stress. Research on model organisms has provided tremendous knowledge of the molecular mechanisms by which NRF2 affects NCDs pathogenesis. This review is a comprehensive summary of the most commonly used model organisms of NCDs in which NRF2 has been genetically or pharmacologically modulated, paving the way for drug development to combat NCDs. We discuss the validity and use of these models and identify future challenges.

PMID:39709790 | DOI:10.1016/j.redox.2024.103464

Lancet. 2025 Dec 21;404(10471):2538-2539. doi: 10.1016/S0140-6736(24)02320-1.

NO ABSTRACT

PMID:39709199 | DOI:10.1016/S0140-6736(24)02320-1

Biochem Pharmacol. 2024 Dec 19:116722. doi: 10.1016/j.bcp.2024.116722. Online ahead of print.

ABSTRACT

Glioblastoma (GB) is the most prevalent and aggressive primary brain tumor with fatal outcome due to a lack of effective treatments. We previously identified C1q-tumor necrosis factor-related protein 8 (CTRP8), a new member of the adiponectin family, as a novel agonist of the relaxin family peptide receptor 1 (RXFP1) and showed that the CTRP8-RXFP1 ligand-receptor system facilitates increased invasiveness and chemoresistance in GB cells. In the present study, we have investigated the role of the CTRP8-RXFP1 signaling axis in glioma progression using an orthotopic mouse model xenografted with human U251 glioma cells stably expressing CTRP8 and RXFP1. Our results demonstrate that this in-vivo U251-CTRP8/RXFP1 glioma model promoted the formation of aggressive, highly proliferative glioma that resulted in significantly shorter survival times of xenografted mice. CTRP8/RXFP1 xenografts showed strongly elevated mitotic activity, increased expression of cathepsin B at the migrating front and promoted a pro-inflammatory tumor microenvironment characterized by a strong upregulation of cytokines, among them eotaxin-2 and-3, interleukin (IL)-6, IL-18 and others. Proteomic analysis of xenografted mouse brain identified both human and mouse proteome signatures unique to CTRP8/RXFP1 xenografts compared to U251 xenografts. In conclusion, our results suggest that co-expression of CTRP8 and RXFP1 promotes signaling pathways that generate unique tissue proteomic and inflammatory cytokine signatures which promote glioma aggressiveness. The CTRP-RXFP1 signaling pathway may represent an effective therapeutic target for the treatment of fast-progressing and currently untreatable GB.

PMID:39709036 | DOI:10.1016/j.bcp.2024.116722

Structure. 2024 Dec 16:S0969-2126(24)00527-6. doi: 10.1016/j.str.2024.11.014. Online ahead of print.

ABSTRACT

Major histocompatibility complex class II (MHC-II) presents antigens to T helper cells. The spectrum of presented peptides is regulated by the exchange catalyst human leukocyte antigen DM (HLA-DM), which dissociates peptide-MHC-II complexes in the endosome. How susceptible a peptide is to HLA-DM is mechanistically not understood. Here, we present a data-driven mathematical model for the conformational landscape of MHC-II that explains the wide range of measured HLA-DM susceptibilities and predicts why some peptides are largely HLA-DM-resistant. We find that the conformational plasticity of MHC-II mediates both allosteric competition and cooperation between peptide and HLA-DM. Competition causes HLA-DM susceptibility to be proportional to the intrinsic peptide off-rate. Remarkably, diverse MHC-II allotypes with conserved HLA-DM interactions show a universal linear susceptibility function. However, HLA-DM-resistant peptides deviate from this susceptibility function; we predict resistance to be caused by fast peptide association with MHC-II. Thus, our study provides quantitative insight into peptide and MHC-II allotype parameters that shape class-II antigen presentation.

PMID:39708815 | DOI:10.1016/j.str.2024.11.014

Curr Biol. 2024 Dec 17:S0960-9822(24)01638-5. doi: 10.1016/j.cub.2024.11.071. Online ahead of print.

ABSTRACT

Metazoan parasites have played a major role in shaping innate immunity in animals. Insect hosts and parasitoid wasps are excellent models for illuminating how animal innate immune systems have evolved to neutralize these enemies. One such strategy relies on symbioses between insects and intracellular bacteria that express phage-encoded toxins. In some cases, the genes that encode these toxins have been horizontally transferred to the genomes of the insects. Here, we used genome editing in Drosophila melanogaster to recapitulate the evolution of two toxin genes-cytolethal distending toxin B (cdtB) and apoptosis inducing protein of 56kDa (aip56)-that were horizontally transferred likely from phages of endosymbiotic bacteria to insects millions of years ago. We found that a cdtB::aip56 fusion gene (fusionB), which is conserved in D. ananassae subgroup species, dramatically promoted fly survival and suppressed parasitoid wasp development when heterologously expressed in D. melanogaster immune tissues. We found that FusionB was a functional nuclease and was secreted into the host hemolymph where it targeted the parasitoid embryo's serosal tissue. Although the mechanism of toxicity remains unknown, when expressed ubiquitously, fusionB resulted in delayed development of late-stage fly larvae and eventually killed pupating flies. These results point to the salience of regulatory constraint in mitigating autoimmunity during the domestication process following horizontal transfer. Our findings demonstrate how horizontal gene transfer can instantly provide new, potent innate immune modules in animals.

PMID:39708795 | DOI:10.1016/j.cub.2024.11.071

STAR Protoc. 2024 Dec 19;6(1):103521. doi: 10.1016/j.xpro.2024.103521. Online ahead of print.

ABSTRACT

Spatial transcriptomics (ST) is fundamental for understanding molecular mechanisms in health and disease. Here, we present a protocol for efficient and high-resolution ST in 2D/3D with Open-ST. We describe all steps for repurposing Illumina flow cells into spatially barcoded capture areas and preparing ST libraries from stained cryosections. We detail the computational workflow for generating 2D/3D molecular maps ("virtual tissue blocks"), aligned with histological data, unlocking molecular pathways in space. Open-ST is applicable to any tissue, including clinical samples. For complete details on the use and execution of this protocol, please refer to Schott et al.1.

PMID:39708325 | DOI:10.1016/j.xpro.2024.103521

Anal Chem. 2024 Dec 21. doi: 10.1021/acs.analchem.4c04166. Online ahead of print.

ABSTRACT

The great variety of antimicrobial resistance (AMR) profiles among tuberculosis (TB) patients necessitates a comprehensive detection method. This study developed culture-independent, long amplicon-based targeted next-generation sequencing (tNGS) methods for predicting AMR across 16 drugs within the Mycobacterium tuberculosis complex (MTBC). Multiplex PCR amplification was employed to enrich 20 gene regions, with sequencing performed on either the Oxford Nanopore Technologies (ONT) or Illumina platforms. Customized bioinformatics pipelines provide a streamlined process from raw data to clinician-friendly reports. The ONT tNGS method has been optimized, and its performance has been thoroughly evaluated, utilizing Q20+ chemistry in combination with the R10.4.1 flow cell. It requires only 15 high-quality reads per target gene to accurately identify all variants, with the turnaround time taking 4 h and 50 min. Studies confirmed that this method effectively identifies Mycobacterium species and was highly resistant to interference from other clinical pathogens. To ensure optimal coverage, it is recommended to input at least 500 copies of the genome and sequence 500MB of high-quality FASTQ data. Diagnostic performance evaluations demonstrate that this method achieves 98.35% concordance with phenotypic drug susceptibility testing (pDST) and is consistent with the results obtained from Xpert MTB/RIF assays. The design of long amplicons not only ensures comprehensive coverage of target regions but also simplifies primer design, facilitating compatibility with various sequencing platforms. Compared with previous studies, the optimized ONT tNGS method in this study significantly improves turnaround time, detection accuracy, and the comprehensive coverage of mutations associated with AMR.

PMID:39707933 | DOI:10.1021/acs.analchem.4c04166

Plant Physiol. 2024 Dec 21:kiae663. doi: 10.1093/plphys/kiae663. Online ahead of print.

ABSTRACT

Phytohormone signaling is fine-tuned by regulatory feedback loops. The phytohormone abscisic acid (ABA) plays key roles in plant development and abiotic stress tolerance. PYRABACTIN RESISTENCE 1/PYR1-LIKE/REGULATORY COMPONENT OF ABA RECEPTOR (PYR/PYL/RCAR) receptors sense ABA, and in turn, ABA represses their expression. Conversely, ABA induces expression of type 2C PROTEIN PHOSPHATASES (PP2C) genes, which negatively regulate the ABA signaling pathway. This regulatory feedback scheme is likely important for modulating ABA signaling. Here, we provide insight into the mechanisms underlying the ABA-induced repression of PYR/PYL/RCAR expression in Arabidopsis (Arabidopsis thaliana). ABA time course analyses revealed strong and sustained repression of PYR/PYL/RCARs, suggesting that receptor gene regulation is an important step in resetting the ABA signaling pathway. Cordycepin-induced transcription inhibition showed that PYL1/4/5/6 mRNA destabilization is involved in the ABA-induced repression of these genes. Furthermore, genetic evidence indicated that decapping may play a role in PYL4/5/6 mRNA decay. We also provide evidence that the Arabidopsis-specific microRNA5628 (miR5628), which is transiently induced by the ABA core signaling pathway, guides PYL6 transcript cleavage in response to ABA. After cleavage, the resulting 5'- and 3'-cleaved fragments of PYL6 mRNA may be degraded by the XRN4 exoribonuclease. miR5628 is an evolutionary novelty that may enhance PYL6 mRNA degradation, along with decapping and XRN4 activity. Thus, regulating the stability of PYR/PYL/RCAR transcripts maintains ABA signaling homeostasis.

PMID:39707902 | DOI:10.1093/plphys/kiae663