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Martin, G.

Publications and source records attributed to Martin, G..

At least 19 recordsLinked to original sources

A COJEC-chemotherapy resistant model of Th-ALK(F1174L)/MYCN neuroblastoma offers insights into tumour immune evasion and development of the bone marrow metastatic niche

Multi-agent COJEC chemotherapy is the main-stay of induction treatment for patients diagnosed with high-risk neuroblastoma. However, at least 10% of patients will be primary refractory to chemotherapy and only 50% achieve 5-year overall survival. The bone marrow is the most frequent site of metastasis in these patients. Novel approaches are required to improve response rates but the inter- and intra- patient tumour heterogeneity and dynamics of the neuroblastoma immune microenvironment makes anticipation of resistance phenotypes incredibly challenging. We present here a novel immunocompetent C57 Bl/6 model of Th-ALK(F1174L)/MYCN neuroblastoma, in which spontaneous abdominal tumours are driven by expression of mutant Anaplastic Lymphoma Kinase and over-expression of Mycn in the neural crest. We have used this model to generate a personalised dosing schedule inducing COJEC-chemotherapy resistance, in which individual mice receive chemotherapy cycles dependent upon the progression of their neuroblastoma tumours. Using both single cell RNA sequencing and spatial immunophenotyping gave us extraordinary precision in our comprehensive analysis of the tumour intrinsic and microenvironmental factors associated with COJEC resistance. We found that the resistance phenotype was driven by Cdk8 upregulation in adrenergic and mesenchymal tumour cells. Infiltration of immunosuppressive myeloid-derived immune cells and remodeling of the tumour-associated stroma further contributed to COJEC resistance. In the bone marrow we observed expansion of neutrophils and evidence of NETosis associated with micro-metastatic disease. Our results further endorse the development of CDK8-targeting therapeutics for neuroblastoma patients which might boost the anti-tumour immune response. Additional studies will be required to define the roles of neutrophils and neutrophil NETosis in neuroblastoma progression and metastasis. Our C57 Bl/6 model will be pivotal in future preclinical studies of immune-modulating therapeutics.

cancer biology↗

Development of a metabolomics-based index to monitor dietary effects on chronic inflammation: The Dietary Metabolomics Inflammation Index

BackgroundThe Dietary Inflammatory Index (DII) is widely used to assess the inflammatory potential of diet, but it relies on self-reported dietary assessment and does not directly capture individual differences in metabolism as an intermediate connection to inflammation. High-resolution metabolomics provides objective measurements that complement dietary assessment to support precision nutrition to control inflammation. ObjectiveWe developed, tested, and applied a Dietary Metabolite Inflammatory Index (DMII) to assess diet-related chronic inflammation using metabolites measured by liquid chromatography-high-resolution mass spectrometry. MethodsDII was calculated using dietaryindex R package with Block Food Frequency Questionnaire (FFQ) data. To develop the DMII, chronic inflammation-related dietary metabolites corresponding to the DII food parameters were found through a literature review. Dietary metabolites were identified and quantified by authentic standards by our established laboratory procedures. DMII uses the same inflammatory effect scores as the DII. Three DMII versions were developed: concentration-based, median-based, and quintile-based DMII. Mean and standard deviation of 29 dietary metabolites were calculated by using 3025 human plasma samples from 3 studies. DMII was tested in the Center for Health Discovery and Well-Being cohort (CHDWB) and the Atlanta African American Maternal and Child cohort (ATLAA) using chronic inflammation biomarkers, including high-sensitivity C-reactive protein (hs-CRP), CRP, and IL-6. The median-based DMII was further applied to four Alzheimers disease metabolomics datasets as a proof-of-concept application. ResultsIn the CHDWB study, concentration-based DMII had a weak positive correlation with Block FFQ-derived DII and strongly correlated with median-based and quintile-based DMII. In the same study, all three DMII versions had significant positive correlations with hs-CRP and IL-6. In the ATLAA study, only concentration-based DMII was positively associated with CRP and IL-6. Higher median-based DMII was associated with higher odds of Alzheimers disease. ConclusionsDMII provides a metabolomics-based framework for assessing diet-related chronic inflammation using metabolomics data. This metabolomics approach may complement self-reported dietary assessment to use diet and nutrition to help protect against chronic disease linked to inflammation.

biochemistry↗

Inferring the multi-host fitness landscape of endive necrotic mosaic virus from cross-inoculation experiments

Fitness landscapes offer a compact representation of adaptation, yet are rarely inferred from sparse multi-environment data. We present a Bayesian approach to infer an effective multi-host phenotypic fitness landscape from cross-inoculation assays by linking successful infection probabilities to Fishers geometrical model and to an explicit decomposition of establishment routes. The model estimates (i) the distance matrix among host-specific phenotypic optima, (ii) target-host permissiveness through the widths of fitness peaks, (iii) target-specific differences in the efficiency with which phenotypic suitability translates into successful infection, and (iv) the conditional probabilities that successful infections are attributed to direct establishment, rescue from standing variation in the source inoculum, or de novo rescue in the target host. We apply the approach to an experimental evolution dataset for endive necrotic mosaic virus evolved on five Asteraceae hosts and challenged in a full cross-inoculation design. The inferred landscape can be visualized as a phenotypic map of the host community, revealing pronounced heterogeneity in target-host permissiveness and a geometry broadly concordant with host phylogeny. By grounding assay-derived distances in an explicit mechanistic model, the approach provides a parsimonious representation of multi-host constraints that can be used to discuss establishment barriers and potential springboard hosts in heterogeneous communities. More broadly, it offers a general method for inferring effective fitness landscapes from sparse multi-environment data.

evolutionary biology↗

Smooth muscle cell estrogen receptor alpha promotes arterial stiffness in the absence of estradiol

BackgroundClinical evidence supports a greater impact of arterial stiffening in cardiovascular mortality in women versus men. Arterial stiffness increases across the menopausal transition, implicating a role of the loss of estrogens in arterial stiffening, but mediating mechanisms remain unclear. MethodsThe role of estradiol and smooth muscle cell (SMC) estrogen receptor alpha (ER) in arterial stiffening, by aortic pulse wave velocity (PWV), was assessed in 3 models: (1) the loss of estradiol in young, female mice comparing sham surgery or bilateral ovariectomy (OVEX) {+/-} estradiol, (2) the impact of sham versus OVEX surgery in young, female SMC-ER-intact and SMC-ER-knockout (KO) littermates, and (3) arterial stiffening during natural aging by comparing young and aged, female and male SMC-ER-intact and SMC-ER-KO littermates. Mechanistic pathways were assessed using histological assessment of aortic fibrosis and elastin degradation, aortic MMP expression, and atomic force microscopy. ResultsOVEX increased PWV and aortic medial fibrosis, with no impact on elastin integrity, in young female mice. Arterial stiffening and fibrosis were prevented in OVEX mice that were supplemented with estradiol. OVEX-induced arterial stiffening in SMC-ER-intact female mice was prevented in SMC-ER-KO littermates. In this model, OVEX was also associated with increased aortic medial fibrosis without changes in elastin integrity. Aging from 3 to 18 months significantly increased PWV in female and male SMC-ER-intact mice. Aging-induced stiffening was fully prevented in female and partially prevented in male SMC-ER-KO mice. SMC-ER contributes to aging-associated arterial stiffening by sex-specific mechanisms, including elastin degradation in females and phenotypic changes in SMC stiffness and probability to form cellular adhesions in males. Circulating estradiol was significantly decreased in serum from aged compared with young female mice. ConclusionsThese findings support that SMC-ER contributes to arterial stiffening in female and male mice in situations where the vasculature is exposed to low levels of estradiol.

physiology↗

Environmental complexity constrains evolutionary adaptation across taxa

Complex environments combining multiple stressors are the new norm worldwide. Adaptive evolution will be critical to population persistence under these combined challenges, but how environmental complexity affects the pace of evolution remains poorly understood. Using a meta-experimental evolution approach, we exposed 14 species, from bacteria to unicellular eukaryotes and plants, to single stressors and their pairwise combinations for multiple generations, while keeping the overall stress level comparable. Populations evolving under combined stressors tended to have lower fitness increase in the selective environments, higher fitness reductions in the control environment, and shallower relation between initial maladaptation and fitness gain, than under single stressors. However, these responses varied with species and stressor type. Accounting for such constraints on evolutionary dynamics should prove crucial for the management of biodiversity. Significance StatementA pressing challenges for modern science and society in the face of ongoing global change is understanding what limits the capacity of living organisms to adapt to complex environments combining multiple stressors. To answer to this question, we conducted a large-scale meta-experimental evolution design across a diversity of organisms, exposing them for multiple generations to either single or combined-stress treatments. Combined stressors led to less adaptive fitness gain than single stressors, and imposed additional costs through reduced fitness in non-stressful conditions. This unique combination of meta-experimental approach with a careful distinction between environmental complexity and overall stress allowed us to gain robust quantitative evidence on how environmental complexity can impact the pace of evolution.

evolutionary biology↗

Alternative splicing of PIF4 regulates plant development under heat stress

The Phytochrome-Interacting Factor 4 (PIF4) is a key player in the integration of multiple internal and external stimuli to optimize different aspects of plant development. While both the DNA encoding this transcription factor and its protein are known to be under tight control, no regulation at the RNA level has been previously reported. Our genomic analysis revealed that the exon/intron structure of the basic Helix-Loop-Helix (bHLH) DNA binding domain of PIF4 is conserved and pointed to skipping of an exon in this region specifically in response to heat stress. We then showed that this alternative splicing event downregulates PIF4 function under heat, which in etiolated seedlings induces photomorphogenic-related traits. Our results disclose a role for PIFs in plant responses to heat and reveal a new regulatory layer for the control of PIF4 function, underscoring the critical role of posttranscriptional regulatory processes in the molecular integration of environmental cues.

plant biology↗

Chlorpyrifos and tamoxifen co-pretreatment promotes stem-like phenotype and upregulation of anti-estrogen therapy resistance markers in ERα breast cancer cells

Endocrine therapy (ET) is the standard first-line treatment for hormone receptor positive breast cancer but about 30% of patients develop resistance. Chlorpyrifos (CPF), is an endocrine disruptor pesticide that promotes a stemness phenotype and triggers molecular mechanisms involved in ET resistance. The goal of this study is to assess whether CPF induces tamoxifen (TAM) resistance by modulating estrogen receptor alpha (RE) expression through histone deacetylase 1 (HDAC1) regulation. We analyzed public databases of breast cancer patients and performed in vitro experiments using the MCF-7 cell line. We evaluated whether the co-pretreatment with CPF and TAM (CPF+TAM) modulates stemness and ET resistance markers. We found that CPF+TAM selects cells that exhibit increased clonogenicity, enhanced mammosphere-forming ability, and upregulates the stemness markers CD44, NANOG and POU5F1 while decreasing CD24. This selected cell subpopulation shows higher levels of mRNA and elevated protein expression of RE and HDAC1. Finally, we identified a resistance and stemness marker signature induced by CPF+TAM that closely resembles the profile observed in the dataset of patients who acquired tamoxifen resistance. Our findings show that CPF promotes an undifferentiated basal-like cell phenotype that contributes to TAM resistance, reinforcing the need for global restrictions to safeguard public health.

cancer biology↗

Rlim coordinates diurnal regulation of food intake and thermogenesis

Energy homeostasis in mice is maintained through coordinated activity among hypothalamic nuclei that regulate food intake and thermogenesis. These processes must adapt to the sleep-wake cycle, yet the underlying pathways, cell types, and molecular mechanisms governing their diurnal regulation remain poorly understood. We show that mice lacking the E3 ubiquitin ligase Rlim are lean and resistant to diet-induced obesity, owing to reduced food intake and enhanced brown adipose tissue (BAT) thermogenesis. We identify GABAergic neurons in the suprachiasmatic nucleus (SCN)--components of the central circadian clock--as mediators of these effects. Specifically, Rlim in RIP-Cre+ neurons governs daily thermogenic rhythms, while Rlim in vasoactive intestinal peptide (VIP)-expressing neurons modulates diurnal feeding behavior. Thus, Rlim is a key regulator of diurnal rhythms controlling energy balance.

physiology↗

Deep learning-enabled scaffolding of spatial arrays of PfCSP epitopes

Malaria is a leading cause of disease in developing countries. The licensed malaria vaccine RTS,S/AS01 confers partial protection in part due to the elicitation of circumsporozoite protein (CSP) antibodies, of which those to the CSP repeat and junctional regions offer the most potent protection. Anti-repeat region antibodies, including the protective antibody L9, frequently develop mutations that promote inter-Fab contacts when bound to CSP in "spiral" quaternary structures. As a first step toward the design of immunogens that elicit L9-like antibodies, we utilized generative deep learning models to design epitope-scaffolds that incorporated up to three junctional repeat epitopes with structural conformations and relative spatial orientations matching those of the multivalent complex of CSP bound to three copies of L9. Affinity and structural studies demonstrated accurate scaffolding of two epitopes with the intended relative orientation, and less accurate positioning of the third epitope. This study demonstrates proof of principle for design of multi-epitope scaffolds with pre-determined relative epitope spatial positioning. The study also represents an initial step toward development of multi-epitope immunogens to elicit antibodies that utilize homotypic interactions to bind pathogen in multivalent clusters.

immunology↗

Cotyledon opening during seedling deetiolation is determined by ABA-mediated splicing regulation

During seedling deetiolation, plants adjust their development to expose photosynthetic tissues to sunlight, enabling the transition from heterotrophic to autotrophic growth. While various plant hormones are known to influence this process, the role of abscisic acid (ABA) remains unclear. Here, we reveal that ABA plays a major role in controlling the dynamics of cotyledon aperture during seedling deetiolation. In darkness, ABA accumulates in the cotyledons to effectively repress their opening. However, light exposure reverses this effect, allowing the cotyledons to open. Our findings indicate that the ABA-mediated regulation of cotyledon dynamics is accompanied by genome-wide rearrangements in both transcriptional and splicing patterns. We demonstrate that the ABA-dependent adjustments of cotyledon and splicing dynamics in response to light depend on the positive role of two splicing factors, RS40 and RS41. Moreover, we identify transcriptional and posttranscriptional mechanisms that repress the activity of these proteins in the dark. Altogether, this work sheds light on the interplay between light and ABA, highlighting a new developmental outcome: cotyledon opening, and identifying a novel layer of gene regulation: alternative splicing.

plant biology↗

A PIF- and GUN1-regulated switch in cell axis growth drives cotyledon expansion through tissue-specific cell expansion and division

Despite its crucial role during seedling deetiolation, cotyledon expansion has been largely overlooked, with hypocotyl elongation favored as the primary phenotypic readout in light signaling research. Here, we investigate how cotyledon expansion is regulated during seedling establishment, and reveal that light-induced cotyledon expansion involves a rapid switch in growth direction - from longitudinal in darkness to transversal upon initial light exposure. Using PIFq- and phyA/phyB-deficient Arabidopsis mutants, we demonstrate that this switch is repressed by PIFs in the dark and promoted by phytochromes under red light. Notably, expansion is antagonistically regulated in the light by GUN1-mediated plastid retrograde signaling. Cotyledon expansion involves rapid epidermis cell expansion, transitioning from rectangular in darkness to characteristic lobed cells in light. Importantly, our findings show that mesophyll extension is driven not only by cell enlargement but also by palisade cell division, consistent with an enrichment of cell cycle-related genes that are antagonistically regulated by the PIF/phy system and retrograde signaling in the cotyledon. Finally, using mutant lines expressing PIF1 and phyB specifically in the epidermis, we establish that epidermal expansion can drive palisade cell growth, while mesophyll cell division is predominantly regulated by light at the tissue-specific level. This study provides a novel framework for investigating cotyledon expansion during seedling deetiolation, incorporating tissue-level regulation. We propose that cotyledons serve as an excellent model for studying morphogenesis and organ geometry, which in plants is governed by directional cell growth. SIGNIFICANT STATEMENTDespite their critical role in the successful establishment of green photoautotrophic organisms, the mechanisms governing cotyledon expansion during seedling deetiolation remain largely unknown. Our study reveals that the phy/PIF system drives a light-induced shift in the cotyledon growth axis to promote cotyledon growth through tissue-specific cell expansion and division, while GUN1-mediated plastid signals counteract this process when chloroplast biogenesis is impaired.

plant biology↗

Morphological map of under- and over-expression of genes in human cells

Cell Painting images offer valuable insights into a cells state and enable many biological applications, but publicly available arrayed datasets only include hundreds of genes perturbed. The JUMP (Joint Undertaking in Morphological Profiling) Cell Painting Consortium perturbed roughly 75% of the protein-coding genome in human U-2 OS cells, generating a rich resource of single-cell images and extracted features. These profiles capture the phenotypic impacts of perturbing 15,243 human genes, including overexpressing 12,609 genes (using open reading frames, ORFs) and knocking out 7,975 genes (using CRISPR-Cas9). We mitigated technical artifacts by rigorously evaluating data processing options and validated the datasets robustness and biological relevance. Analysis of phenotypic profiles revealed novel gene clusters and functional relationships, including those associated with mitochondrial function, cancer, and neural processes. The JUMP Cell Painting genetic dataset is a valuable resource for exploring gene relationships and uncovering novel functions.

bioinformatics↗

A Comprehensive Bibliometric Investigation on Antimicrobials from Fungal Origins with a Biotechnological Perspective

Interest in research related to fungi exploration past few years, given its relevance to bioactive compounds production as these metabolites are a promising source of bacteriostatic or fungistatic compounds. Therefore, their use represents a significant alternative to traditional antibiotics by minimizing the risks related to microbial resistance. In this context, this work aimed to: assess the volume of annual publications on the subject and identify key players, analyze the collaboration network among researchers, and check the patents filed on this topic. For this purpose, the Bibliometrix R-package was used, as well as scientific metadata from the Web of Science and Scopus databases (n=506). In total, 256 sources, authors (n=2,526), keywords (n=1,812), and references (n=19,315) were analyzed from 1989 to 2023. The academic debate on the subject has been promoted by India (29%), United Kingdom (UK) (7%), China (6%) and the United States of America (USA) (6%). The authors identified as the most cited were Liu J (n=142), followed by Jesu Arockiaraj (n=106). There is a knowledge predominance of publications focusing on the life science disciplines. The most prolific institutions were the National Research Center (n=20) and the University of Pittsburgh (n=13). The most cited journals were the World Journal of Microbiology & Biotechnology (n=719) and Applied Microbiology and Biotechnology (n=661). Finally, the United States Patent and Trademark Office represented 85% of the patents filed on the subject (n=28,303). Together, these results can direct researchers and Biotech industries in their search for the most important sources related to antimicrobial biotechnology.

microbiology↗

ALDH1 subtype-specific inhibitor targets key cell populations in triple negative breast cancer

Aggressive breast cancer subtypes, particularly triple-negative breast cancer (TNBC), lack effective targeted therapies, requiring novel approaches. This study focuses on the aldehyde dehydrogenase 1A (ALDH1A) subfamily, comprising ALDH1A1, ALDH1A2, and ALDH1A3, and their roles in tumor biology and the tumor microenvironment. Comprehensive transcriptomic and single-cell analyses revealed subtype- and cell-specific expression patterns of ALDH1A isoforms, with ALDH1A3 predominantly expressed in epithelial cancer cells of basal-like tumors, while ALDH1A1 and ALDH1A2 were expressed in stromal and immune-associated subpopulations. Guided by these findings, we developed ABD0171, a selective ALDH1A3 inhibitor that demonstrated potent isoform-specific activity. ABD0171 effectively disrupted key pathways in TNBC cells in vitro, including IL6/JAK/STAT3, tPA and Src/FAK, and exhibited superior selectivity, robust antitumor and antimetastatic effects, and a favorable safety profile in vivo. These results establish ALDH1A3 as a promising therapeutic target and validate ABD0171 as a candidate to address current challenges in aggressive breast cancers.

cancer biology↗

An orbitocortical-thalamic circuit suppresses binge alcohol-drinking.

Alcohol consumption remains a significant global health challenge, causing millions of direct and indirect deaths annually. Intriguingly, recent work has highlighted the prefrontal cortex, a major brain area that regulates inhibitory control of behaviors, whose activity becomes dysregulated upon alcohol abuse. However, whether an endogenous mechanism exists within this brain area that limits alcohol consumption is unknown. Here we identify a discrete GABAergic neuronal ensemble in the medial orbitofrontal cortex (mOFC) that is selectively recruited during binge alcohol-drinking and intoxication. Upon alcohol intoxication, this neuronal ensemble suppresses binge drinking behavior. Optogenetically silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. We find that this neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. We further show, using brain-wide analysis, that this neuronal ensemble projects widely, and that its projections specifically to the mediodorsal thalamus are responsible for regulating binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by halting alcohol intake. These results provide valuable insights into the complex nature of alcohol abuse and offers potential avenues for the development of mOFC neuronal ensemble-targeted interventions.

neuroscience↗

Painting the diversity of a world's favourite fruit: A next generation catalogue of cultivated bananas

Societal impact statementBananas are nutritious fruits of major importance in the tropics and subtropics. Characterizing their diversity is essential to ensure their conservation and use. A catalogue showcasing cultivated bananas genomic diversity was compiled and is to be used as a tool to support the classification of banana cultivars. This research revealed that cultivated banana groups are not all made of identical clones. Materials from recent collecting missions indicated that more banana diversity is expected to be found as the exploration of the banana gene pool continues. These discoveries will drive dynamic conservation strategies for banana genetic resources and will increase their use. SummaryO_LIBanana is an important food crop cultivated in many tropical and subtropical regions around the world. Due to their low fertility, banana landraces are clonally propagated. However, different factors, such as synonymy and the effects of environment, make their assignment to described sets of clones, or cultivar groups, difficult. Consequently, passport data of accessions in genebanks is often uncomplete and sometimes inaccurate. C_LIO_LIWith the recent advances in genomics, a new powerful tool was developed enabling the fine-scale characterization of bananas ancestry along chromosomes, i.e. in silico chromosome painting. We applied this method to a high-throughput genotyping data set obtained from 317 banana accessions spanning most of the known cultivar groups. This set included both genebank and new uncharacterized materials. C_LIO_LIBy comparing curated morphological assignation to the genomic patterns resulting from in silico chromosome painting, we were able to compile a catalogue referencing the chromosome painting patterns of most of the described cultivar groups. C_LIO_LIExamining the genomic patterns obtained, we discovered intra-cultivar group variability. In some cultivar groups, mitotic recombination or deletions were clonally accumulated in cultivars. In addition, we identified at least 4 cultivar groups in which cultivars likely resulting from distinct sexual events co-existed, notably Pisang Awak in which 5 distinct genomic patterns of two ploidy levels were identified. New patterns were also discovered in the newest materials of the set, showing that a wider diversity of clones still exist on farm. C_LI

genomics↗

Marigold: A machine learning-based web app for zebrafish pose tracking

High-throughput behavioral analysis is important for drug discovery, toxicological studies, and the modeling of neurological disorders such as autism and epilepsy. Zebrafish embryos and larvae are ideal for such applications because they are spawned in large clutches, develop rapidly, feature a relatively simple nervous system, and have orthologs to many human disease genes. However, existing software for video-based behavioral analysis can be incompatible with recordings that contain dynamic backgrounds or foreign objects, lack support for multiwell formats, require expensive hardware, and/or demand considerable programming expertise. Here, we introduce Marigold, a free and open source web app for high-throughput behavioral analysis of embryonic and larval zebrafish. Marigold features an intuitive graphical user interface (GUI), tracks up to 10 user-defined keypoints, supports both single- and multiwell formats, and exports a range of kinematic parameters in addition to publication-quality data visualizations. By leveraging a highly efficient, custom-designed neural network architecture, Marigold achieves reasonable training and inference speeds even on modestly powered computers lacking a discrete graphics processing unit (GPU). Notably, as a web app, Marigold does not require any installation and runs within popular web browsers on ChromeOS, Linux, macOS, and Windows. To demonstrate Marigolds utility, we conducted two sets of biological experiments. First, we examined novel aspects of the touch-evoked escape response in techno trousers (tnt) mutant embryos, which contain a previously described loss-of-function mutation in the gene encoding Eaat2b, a glial glutamate transporter. We identified differences and interactions between touch location (head vs. tail) and genotype. Second, we investigated the effects of feeding on larval visuomotor behavior at 5 and 7 days post-fertilization (dpf). We found differences in the number and vigor of swimming bouts between fed and unfed fish at both time points, as well as interactions between developmental stage and feeding regimen. In both biological experiments presented here, the use of Marigold facilitated novel behavioral findings. Marigolds ease of use, robust pose tracking, amenability to diverse experimental paradigms, and flexibility regarding hardware requirements make it a powerful tool for analyzing zebrafish behavior, especially in low-resource settings such as course-based undergraduate research experiences (CUREs). Marigold is available at: https://downeslab.github.io/marigold/.

animal behavior and cognition↗

An Arabidopsis SR protein relieving ABA inhibition of seedling establishment represses ABA-responsive alternative splicing

The phytohormone abscisic acid (ABA) inhibits postgerminative growth under unfavorable conditions to delay the transition to the autotrophic stage and promote plant survival. While stress-induced ABA accumulation is well established to trigger extensive transcriptional changes, it is becoming clear that it also relies on alternative splicing to enhance stress tolerance. However, the upstream components modulating posttranscriptional regulation of the ABA response remain largely unknown. Here, we show that loss of function of the Arabidopsis SR34a protein enhances sensitivity to ABA during seedling establishment. Individual-nucleotide crosslinking and immunoprecipitation (iCLIP) combined with RNA-sequencing revealed that SR34a is an alternative splicing regulator that binds predominantly GCU-rich exonic sequences near splice sites. We find that SR34a targets all alternative splicing event types, including in RNAs encoding known determinants of ABA sensitivity, to prevent ABA-responsive splicing in germinated seeds. Our study sheds mechanistic light on how plant SR proteins regulate alternative splicing and counteract ABA inhibition of early plant growth.

plant biology↗