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The Plant Cell Jun 2024N 6-methyladenosine (m6A) is the most abundant mRNA modification and plays diverse roles in eukaryotes, including plants. It regulates various processes, including plant...
N 6-methyladenosine (m6A) is the most abundant mRNA modification and plays diverse roles in eukaryotes, including plants. It regulates various processes, including plant growth, development, and responses to external or internal stress responses. However, the mechanisms underlying how m6A is related to environmental stresses in both mammals and plants remain elusive. Here, we identified EVOLUTIONARILY CONSERVED C-TERMINAL REGION 8 (ECT8) as an m6A reader protein and showed that its m6A-binding capability is required for salt stress responses in Arabidopsis (Arabidopsis thaliana). ECT8 accelerates the degradation of its target transcripts through direct interaction with the decapping protein DECAPPING 5 within processing bodies. We observed a significant increase in the ECT8 expression level under various environmental stresses. Using salt stress as a representative stressor, we found that the transcript and protein levels of ECT8 rise in response to salt stress. The increased abundance of ECT8 protein results in the enhanced binding capability to m6A-modified mRNAs, thereby accelerating their degradation, especially those of negative regulators of salt stress responses. Our results demonstrated that ECT8 acts as an abiotic stress sensor, facilitating mRNA decay, which is vital for maintaining transcriptome homeostasis and enhancing stress tolerance in plants. Our findings not only advance the understanding of epitranscriptomic gene regulation but also offer potential applications for breeding more resilient crops in the face of rapidly changing environmental conditions.
PubMed: 38835286
DOI: 10.1093/plcell/koae149 -
Brain : a Journal of Neurology Jun 2024Congenital hydrocephalus (CH), characterized by cerebral ventriculomegaly, is one of the most common reasons for pediatric brain surgery. Recent studies have implicated...
Congenital hydrocephalus (CH), characterized by cerebral ventriculomegaly, is one of the most common reasons for pediatric brain surgery. Recent studies have implicated lin-41 (lineage variant 41)/TRIM71 (tripartite motif 71) as a candidate CH risk gene, however, TRIM71 variants have not been systematically examined in a large patient cohort or conclusively linked with an OMIM syndrome. Through cross-sectional analysis of the largest assembled cohort of patients with cerebral ventriculomegaly, including neurosurgically-treated CH (totaling 2,697 parent-proband trios and 8,091 total exomes), we identified 13 protein-altering de novo variants (DNVs) in TRIM71 in unrelated children exhibiting variable ventriculomegaly, CH, developmental delay, dysmorphic features, and other structural brain defects including corpus callosum dysgenesis and white matter hypoplasia. Eight unrelated patients were found to harbor arginine variants, including two recurrent missense DNVs, at homologous positions in RPXGV motifs of different NHL domains. Seven additional patients with rare, damaging, unphased or transmitted variants of uncertain significance were also identified. NHL-domain variants of TRIM71 exhibited impaired binding to the canonical TRIM71 target CDKN1A; other variants failed to direct the subcellular localization of TRIM71 to processing bodies. Single-cell transcriptomic analysis of human embryos revealed expression of TRIM71 in early first-trimester neural stem cells of the brain. These data show TRIM71 is essential for human brain morphogenesis and that TRIM71 mutations cause a novel neurodevelopmental syndrome featuring ventriculomegaly and CH.
PubMed: 38833623
DOI: 10.1093/brain/awae175 -
Proceedings of the National Academy of... Jun 2024Human pose, defined as the spatial relationships between body parts, carries instrumental information supporting the understanding of motion and action of a person. A...
Human pose, defined as the spatial relationships between body parts, carries instrumental information supporting the understanding of motion and action of a person. A substantial body of previous work has identified cortical areas responsive to images of bodies and different body parts. However, the neural basis underlying the visual perception of body part relationships has received less attention. To broaden our understanding of body perception, we analyzed high-resolution fMRI responses to a wide range of poses from over 4,000 complex natural scenes. Using ground-truth annotations and an application of three-dimensional (3D) pose reconstruction algorithms, we compared similarity patterns of cortical activity with similarity patterns built from human pose models with different levels of depth availability and viewpoint dependency. Targeting the challenge of explaining variance in complex natural image responses with interpretable models, we achieved statistically significant correlations between pose models and cortical activity patterns (though performance levels are substantially lower than the noise ceiling). We found that the 3D view-independent pose model, compared with two-dimensional models, better captures the activation from distinct cortical areas, including the right posterior superior temporal sulcus (pSTS). These areas, together with other pose-selective regions in the LOTC, form a broader, distributed cortical network with greater view-tolerance in more anterior patches. We interpret these findings in light of the computational complexity of natural body images, the wide range of visual tasks supported by pose structures, and possible shared principles for view-invariant processing between articulated objects and ordinary, rigid objects.
Topics: Humans; Magnetic Resonance Imaging; Male; Female; Adult; Brain; Brain Mapping; Visual Perception; Posture; Young Adult; Imaging, Three-Dimensional; Photic Stimulation; Algorithms
PubMed: 38830105
DOI: 10.1073/pnas.2317707121 -
Frontiers in Psychiatry 2024Body image dissatisfaction has emerged as an important determinant of dietary and physical activity, which in turn determine adolescents' nutritional status. Hence, it...
PURPOSE
Body image dissatisfaction has emerged as an important determinant of dietary and physical activity, which in turn determine adolescents' nutritional status. Hence, it is important to understand predictors of body image dissatisfaction. Therefore, this study aimed to assess body image dissatisfaction and its associated factors among secondary school adolescents in the study area.
METHODS
Data collected for other purposes were used to assess body image dissatisfaction among adolescents in Harar town. Body image dissatisfaction was assessed using the Body Part Satisfaction Scale. Data processing and analysis were performed using STATA version 14, and binary logistic regression was used to identify factors associated with body image dissatisfaction. Factors associated with body image dissatisfaction were determined by estimating AOR along with 95% CI and the statistical significance was declared at a p-value less than or equal to 0.05.
RESULT
The prevalence of body image dissatisfaction was 22.06% [95% CI (19.63, 24.70)]. This study also revealed that males were more dissatisfied with their upper torso and face, and females were more dissatisfied with their middle torso, lower torso, height, and weight than males. In this study, body image dissatisfaction was associated with perception of being fat [AOR = 1.89, 95% CI (1.23, 2.91)], anxiety [AOR = 1.59, 95% CI (1.02, 2.48)], and cigarette smoking [AOR = 1.63, 95% CI (1.03, 2.58)].
CONCLUSION
Almost one in five secondary school adolescents in Harar had body image dissatisfaction, which was significantly associated with perceptions of being fat, anxiety, and smoking. In this study, a significant number of the adolescents experienced body image dissatisfaction. Hence, all concerned bodies have to take action to reduce the burden.
PubMed: 38827436
DOI: 10.3389/fpsyt.2024.1397155 -
Frontiers in Cellular Neuroscience 2024Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Current therapies primarily target the inflammatory component...
INTRODUCTION
Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Current therapies primarily target the inflammatory component of the disease and are highly effective in early stages of MS while limited therapies have an effect in the more chronic progressive stages of MS where resident glia have a larger role. MS lesions tend to be inflammatory even after the initial peripheral immune cell invasion has subsided and this inflammation is known to cause alternative splicing events.
METHODS
We used qPCR of normal-appearing white matter and white matter lesions from postmortem MS tissue, studies, and immunostaining in MS tissue to investigate the alternative splicing of one gene known to be important during recovery in an animal model of MS, .
RESULTS
We found a novel, intron-retained isoform which has not been annotated, upregulated specifically in MS patient white matter lesions. We found that this novel isoform activates the nonsense-mediated decay pathway in primary human astrocytes, the most populous glial cell in the CNS, and is then degraded. Overexpression of this isoform in astrocytes leads to an increased number of processing bodies , the primary site of mRNA decay. Finally, we demonstrated that MS white matter lesions have a higher burden of processing bodies compared to normal-appearing white matter, predominantly in GFAP-positive astrocytes.
DISCUSSION
The increase in alternative splicing of the gene, the stress that this alternative splicing causes, and the observation that processing bodies are increased in white matter lesions suggests that the lesion microenvironment may lead to increased alternative splicing of many genes. This alternative splicing may blunt the protective or reparative responses of resident glia in and around white matter lesions in MS patients.
PubMed: 38812791
DOI: 10.3389/fncel.2024.1379261 -
The Journal of Biological Chemistry May 2024Ataxin-2 (Atx2) is a polyglutamine (polyQ) tract-containing RNA-binding protein, while its polyQ expansion may cause protein aggregation that is implicated in the...
Ataxin-2 (Atx2) is a polyglutamine (polyQ) tract-containing RNA-binding protein, while its polyQ expansion may cause protein aggregation that is implicated in the pathogenesis of neurodegenerative diseases such as spinocerebellar ataxia type 2 (SCA2). However, the molecular mechanism underlying how Atx2 aggregation contributes to the proteinopathies remains elusive. Here, we investigated the influence of Atx2 aggregation on the assembly and functionality of cellular processing bodies (P-bodies) by using biochemical and fluorescence imaging approaches. We have revealed that polyQ-expanded (PQE) Atx2 sequesters the DEAD-box RNA helicase (DDX6), an essential component of P-bodies, into aggregates or puncta via some RNA sequences. The N-terminal like-Sm (LSm) domain of Atx2 (residues 82-184) and the C-terminal helicase domain of DDX6 are responsible for the interaction and specific sequestration. Moreover, sequestration of DDX6 may aggravate pre-mRNA mis-splicing, and interfere with the assembly of cellular P-bodies, releasing the endoribonuclease MARF1 that promotes mRNA decay and translational repression. Rescuing the DDX6 protein level can recover the assembly and functionality of P-bodies, preventing targeted mRNA from degradation. This study provides a line of evidence for sequestration of the P-body components and impairment of the P-body homeostasis in dysregulating RNA metabolism, which is implicated in the disease pathologies and a potential therapeutic target.
PubMed: 38810698
DOI: 10.1016/j.jbc.2024.107413 -
Current Biology : CB Jun 2024The mitochondrial proteome is comprised of approximately 1,100 proteins, all but 12 of which are encoded by the nuclear genome in C. elegans. The expression of...
The mitochondrial proteome is comprised of approximately 1,100 proteins, all but 12 of which are encoded by the nuclear genome in C. elegans. The expression of nuclear-encoded mitochondrial proteins varies widely across cell lineages and metabolic states, but the factors that specify these programs are not known. Here, we identify mutations in two nuclear-localized mRNA processing proteins, CMTR1/CMTR-1 and SRRT/ARS2/SRRT-1, which we show act via the same mechanism to rescue the mitochondrial complex I mutant NDUFS2/gas-1(fc21). CMTR-1 is an FtsJ-family RNA methyltransferase that, in mammals, 2'-O-methylates the first nucleotide 3' to the mRNA CAP to promote RNA stability and translation. The mutations isolated in cmtr-1 are dominant and lie exclusively in the regulatory G-patch domain. SRRT-1 is an RNA binding partner of the nuclear cap-binding complex and determines mRNA transcript fate. We show that cmtr-1 and srrt-1 mutations activate embryonic expression of NDUFS2/nduf-2.2, a paralog of NDUFS2/gas-1 normally expressed only in dopaminergic neurons, and that nduf-2.2 is necessary for the complex I rescue by the cmtr-1 G-patch mutant. Additionally, we find that loss of the cmtr-1 G-patch domain cause ectopic localization of CMTR-1 protein to processing bodies (P bodies), phase-separated organelles involved in mRNA storage and decay. P-body localization of the G-patch mutant CMTR-1 contributes to the rescue of the hyperoxia sensitivity of the NDUFS2/gas-1 mutant. This study suggests that mRNA methylation at P bodies may control nduf-2.2 gene expression, with broader implications for how the mitochondrial proteome is translationally remodeled in the face of tissue-specific metabolic requirements and stress.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Electron Transport Complex I; Dopaminergic Neurons; Mutation; Methyltransferases; Mitochondria; Mitochondrial Proteins; NADH Dehydrogenase
PubMed: 38810637
DOI: 10.1016/j.cub.2024.04.079 -
Journal of Neurophysiology Jul 2024Closing our eyes largely shuts down our ability to see. That said, our eyelids still pass some light, allowing our visual system to coarsely process information about...
Closing our eyes largely shuts down our ability to see. That said, our eyelids still pass some light, allowing our visual system to coarsely process information about visual scenes, such as changes in luminance. However, the specific impact of eye closure on processing within the early visual system remains largely unknown. To understand how visual processing is modulated when eyes are shut, we used functional magnetic resonance imaging (fMRI) to measure responses to a flickering visual stimulus at high (100%) and low (10%) temporal contrasts, while participants viewed the stimuli with their eyes open or closed. Interestingly, we discovered that eye closure produced a qualitatively distinct pattern of effects across the visual thalamus and visual cortex. We found that with eyes open, low temporal contrast stimuli produced smaller responses across the lateral geniculate nucleus (LGN), primary (V1) and extrastriate visual cortex (V2). However, with eyes closed, we discovered that the LGN and V1 maintained similar blood oxygenation level-dependent (BOLD) responses as the eyes open condition, despite the suppressed visual input through the eyelid. In contrast, V2 and V3 had strongly attenuated BOLD response when eyes were closed, regardless of temporal contrast. Our findings reveal a qualitatively distinct pattern of visual processing when the eyes are closed-one that is not simply an overall attenuation but rather reflects distinct responses across visual thalamocortical networks, wherein the earliest stages of processing preserve information about stimuli but are then gated off downstream in visual cortex. When we close our eyes coarse luminance information is still accessible by the visual system. Using functional magnetic resonance imaging, we examined whether eyelid closure plays a unique role in visual processing. We discovered that while the LGN and V1 show equivalent responses when the eyes are open or closed, extrastriate cortex exhibited attenuated responses with eye closure. This suggests that when the eyes are closed, downstream visual processing is blind to this information.
Topics: Humans; Male; Female; Adult; Visual Cortex; Magnetic Resonance Imaging; Geniculate Bodies; Young Adult; Visual Perception; Visual Pathways; Thalamus; Photic Stimulation; Brain Mapping
PubMed: 38810261
DOI: 10.1152/jn.00073.2024 -
PloS One 2024In the realm of industrial inspection, the precise assessment of internal thread quality is crucial for ensuring mechanical integrity and safety. However, challenges...
In the realm of industrial inspection, the precise assessment of internal thread quality is crucial for ensuring mechanical integrity and safety. However, challenges such as limited internal space, inadequate lighting, and complex geometry significantly hinder high-precision inspection. In this study, we propose an innovative automated internal thread detection scheme based on machine vision, aimed at addressing the time-consuming and inefficient issues of traditional manual inspection methods. Compared with other existing technologies, this research significantly improves the speed of internal thread image acquisition through the optimization of lighting and image capturing devices. To effectively tackle the challenge of image stitching for complex thread textures, an internal thread image stitching technique based on a cylindrical model is proposed, generating a full-view thread image. The use of the YOLOv8 model for precise defect localization in threads enhances the accuracy and efficiency of detection. This system provides an efficient and intuitive artificial intelligence solution for detecting surface defects on geometric bodies in confined spaces.
Topics: Image Processing, Computer-Assisted; Algorithms; Artificial Intelligence
PubMed: 38805511
DOI: 10.1371/journal.pone.0304224 -
Nucleic Acids Research May 2024The RNA polymerase II carboxy-terminal domain (CTD) consists of conserved heptapeptide repeats that can be phosphorylated to influence distinct stages of the...
The RNA polymerase II carboxy-terminal domain (CTD) consists of conserved heptapeptide repeats that can be phosphorylated to influence distinct stages of the transcription cycle, including RNA processing. Although CTD-associated proteins have been identified, phospho-dependent CTD interactions have remained elusive. Proximity-dependent biotinylation (PDB) has recently emerged as an alternative approach to identify protein-protein associations in the native cellular environment. In this study, we present a PDB-based map of the fission yeast RNAPII CTD interactome in living cells and identify phospho-dependent CTD interactions by using a mutant in which Ser2 was replaced by alanine in every repeat of the fission yeast CTD. This approach revealed that CTD Ser2 phosphorylation is critical for the association between RNAPII and the histone methyltransferase Set2 during transcription elongation, but is not required for 3' end processing and transcription termination. Accordingly, loss of CTD Ser2 phosphorylation causes a global increase in antisense transcription, correlating with elevated histone acetylation in gene bodies. Our findings reveal that the fundamental role of CTD Ser2 phosphorylation is to establish a chromatin-based repressive state that prevents cryptic intragenic transcription initiation.
PubMed: 38801067
DOI: 10.1093/nar/gkae436