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The Journal of Cell Biology Nov 2023The c-Jun N-terminal kinase (JNK) regulates various important physiological processes. Although the JNK pathway has been under intense investigation for over 20 yr, its...
The c-Jun N-terminal kinase (JNK) regulates various important physiological processes. Although the JNK pathway has been under intense investigation for over 20 yr, its complexity is still perplexing, with multiple protein partners underlying the diversity of its activity. We show that JNK is associated with the basal bodies in both primary and motile cilia. Loss of JNK disrupts basal body migration and docking and leads to severe ciliogenesis defects. JNK's involvement in ciliogenesis stems from a dual role in the regulation of the actin networks of multiciliated cells (MCCs) and the establishment of the intraflagellar transport-B core complex. JNK signaling is also critical for the maintenance of the actin networks and ciliary function in mature MCCs. JNK is implicated in the development of diabetes, neurodegeneration, and liver disease, all of which have been linked to ciliary dysfunction. Our work uncovers a novel role of JNK in ciliogenesis and ciliary function that could have important implications for JNK's role in the disease.
Topics: Actins; Cilia; MAP Kinase Signaling System; Phosphorylation; Protein Processing, Post-Translational; JNK Mitogen-Activated Protein Kinases
PubMed: 37851005
DOI: 10.1083/jcb.202303052 -
Nature Communications Nov 2023In the mammalian visual system, the ventral lateral geniculate nucleus (vLGN) of the thalamus receives salient visual input from the retina and sends prominent GABAergic...
In the mammalian visual system, the ventral lateral geniculate nucleus (vLGN) of the thalamus receives salient visual input from the retina and sends prominent GABAergic axons to the superior colliculus (SC). However, whether and how vLGN contributes to fundamental visual information processing remains largely unclear. Here, we report in mice that vLGN facilitates visually-guided approaching behavior mediated by the lateral SC and enhances the sensitivity of visual object detection. This can be attributed to the extremely broad spatial integration of vLGN neurons, as reflected in their much lower preferred spatial frequencies and broader spatial receptive fields than SC neurons. Through GABAergic thalamocollicular projections, vLGN specifically exerts prominent surround suppression of visuospatial processing in SC, leading to a fine tuning of SC preferences to higher spatial frequencies and smaller objects in a context-dependent manner. Thus, as an essential component of the central visual processing pathway, vLGN serves to refine and contextually modulate visuospatial processing in SC-mediated visuomotor behaviors via visually-driven long-range feedforward inhibition.
Topics: Mice; Animals; Geniculate Bodies; Neurons; Thalamus; Visual Pathways; Superior Colliculi; Mammals
PubMed: 37949869
DOI: 10.1038/s41467-023-43147-9 -
Frontiers in Plant Science 2022Phytochromes are red- and far-red light receptors that control the growth and development of plants, enabling them to respond adequately to changing light conditions. It...
Phytochromes are red- and far-red light receptors that control the growth and development of plants, enabling them to respond adequately to changing light conditions. It has been shown that halted mRNAs stored in RNA granules called processing bodies are released upon light perception and contribute to the adaptation to the light environment. However, the photophysiological background of this process is largely unknown. We found that light of different wavelengths can trigger the disassembly of processing bodies in a dose- and time-dependent manner. We show that phytochromes control this process in red- and far-red light and that cytoplasmic phytochrome A is sufficient and necessary for the far-red light-induced disassembly of processing bodies. This adds a novel, unexpected cytoplasmic function to the processes controlled by phytochrome A. Overall, our findings suggest a role of phytochromes in the control of translationally halted mRNAs that are stored in processing bodies. We expect our findings to facilitate understanding of how light and environmental cues control the assembly and disassembly of processing bodies, which could have broader implications for the regulation of non-membranous organelles in general.
PubMed: 35283917
DOI: 10.3389/fpls.2022.828529 -
Bioresources and Bioprocessing 2021The Global Diabetes Compact was launched by the World Health Organization in April 2021 with one of its important goals to increase the accessibility and affordability... (Review)
Review
The Global Diabetes Compact was launched by the World Health Organization in April 2021 with one of its important goals to increase the accessibility and affordability of life-saving medicine-insulin. The rising prevalence of diabetes worldwide is bound to escalate the demand for recombinant insulin therapeutics, and currently, the majority of recombinant insulin therapeutics are produced from inclusion bodies. Here, a comprehensive review of downstream processing of recombinant human insulin/analogue production from inclusion bodies is presented All the critical aspects of downstream processing, starting from proinsulin recovery from inclusion bodies, inclusion body washing, inclusion body solubilization and oxidative sulfitolysis, cyanogen bromide cleavage, buffer exchange, purification by chromatography, pH precipitation and zinc crystallization methods, proinsulin refolding, enzymatic cleavage, and formulation, are explained in this review. Pertinent examples are summarized and the practical aspects of integrating every procedure into a multimodal purification scheme are critically discussed. In the face of increasing global demand for insulin product, there is a pressing need to develop a more efficient and economical production process. The information presented would be insightful to all the manufacturers and stakeholders for the production of human insulins, insulin analogues or biosimilars, as they strive to make further progresses in therapeutic recombinant insulin development and production.
PubMed: 34336550
DOI: 10.1186/s40643-021-00419-w -
Nucleic Acids Research Dec 2020Eukaryotic cells compartmentalize their internal milieu in order to achieve specific reactions in time and space. This organization in distinct compartments is essential... (Review)
Review
Eukaryotic cells compartmentalize their internal milieu in order to achieve specific reactions in time and space. This organization in distinct compartments is essential to allow subcellular processing of regulatory signals and generate specific cellular responses. In the nucleus, genetic information is packaged in the form of chromatin, an organized and repeated nucleoprotein structure that is a source of epigenetic information. In addition, cells organize the distribution of macromolecules via various membrane-less nuclear organelles, which have gathered considerable attention in the last few years. The macromolecular multiprotein complexes known as Promyelocytic Leukemia Nuclear Bodies (PML NBs) are an archetype for nuclear membrane-less organelles. Chromatin interactions with nuclear bodies are important to regulate genome function. In this review, we will focus on the dynamic interplay between PML NBs and chromatin. We report how the structure and formation of PML NBs, which may involve phase separation mechanisms, might impact their functions in the regulation of chromatin dynamics. In particular, we will discuss how PML NBs participate in the chromatinization of viral genomes, as well as in the control of specific cellular chromatin assembly pathways which govern physiological mechanisms such as senescence or telomere maintenance.
Topics: Cell Nucleus; Cellular Senescence; Chromatin; Chromatin Assembly and Disassembly; Genome, Human; Genome, Viral; Histones; Host-Pathogen Interactions; Humans; Intranuclear Inclusion Bodies; Promyelocytic Leukemia Protein; Protein Processing, Post-Translational; Small Ubiquitin-Related Modifier Proteins; Sumoylation; Telomere Homeostasis; Viruses
PubMed: 33068409
DOI: 10.1093/nar/gkaa828 -
Trends in Neurosciences Jul 2022The construction of complex engrams requires hippocampal-cortical interactions. These include both direct interactions and ones via often-overlooked subcortical loops.... (Review)
Review
The construction of complex engrams requires hippocampal-cortical interactions. These include both direct interactions and ones via often-overlooked subcortical loops. Here, we review the anatomical organization of a hierarchy of parallel 'Papez' loops through the hypothalamus that are homologous in mammals from rats to humans. These hypothalamic loops supplement direct hippocampal-cortical connections with iterative reprocessing paced by theta rhythmicity. We couple existing anatomy and lesion data with theory to propose that recirculation in these loops progressively enhances desired connections, while reducing interference from competing external goals and internal associations. This increases the signal-to-noise ratio in the distributed engrams (neocortical and cerebellar) necessary for complex learning and memory. The hypothalamic nodes provide key motivational input for engram enhancement during consolidation.
Topics: Animals; Cerebellum; Hippocampus; Humans; Hypothalamus; Learning; Mammals; Neural Pathways; Rats; Theta Rhythm
PubMed: 35599065
DOI: 10.1016/j.tins.2022.04.006 -
Brain Sciences Jan 2023Body inversion effects (BIEs) reflect the deployment of the configural processing of body stimuli. BIE modulates the activity of body-selective areas within both the...
Body inversion effects (BIEs) reflect the deployment of the configural processing of body stimuli. BIE modulates the activity of body-selective areas within both the dorsal and the ventral streams, which are tuned to low (LSF) or high spatial frequencies (HSF), respectively. The specific contribution of different bands to the configural processing of bodies along gender and posture dimensions, however, is still unclear. Seventy-two participants performed a delayed matching-to-sample paradigm in which upright and inverted bodies, differing for gender or posture, could be presented in their original intact form or in the LSF- or HSF-filtered version. In the gender discrimination task, participants' performance was enhanced by the presentation of HSF images. Conversely, for the posture discrimination task, a better performance was shown for either HSF or LSF images. Importantly, comparing the amount of BIE across spatial-frequency conditions, we found greater BIEs for HSF than LSF images in both tasks, indicating that configural body processing may be better supported by HSF information, which will bias processing in the ventral stream areas. Finally, the exploitation of HSF information for the configural processing of body postures was lower in individuals with higher autistic traits, likely reflecting a stronger reliance on the local processing of body-part details.
PubMed: 36831733
DOI: 10.3390/brainsci13020190 -
International Journal of Health Policy... Jul 2022Food systems affect nutritional and other health outcomes. Recent literature from India has described policy aspects addressing nutritional implications of specific... (Review)
Review
BACKGROUND
Food systems affect nutritional and other health outcomes. Recent literature from India has described policy aspects addressing nutritional implications of specific foods (eg, fruits, vegetables, and trans-fats), and identified opportunities to tackle the double burden of malnutrition. This paper attempts to deepen the understanding on how health concerns and the role of the health sector are addressed across food systems policies in India.
METHODS
This qualitative study used two approaches; namely (i) the framework method and (ii) manifest content analysis, to investigate national-level policy documents from relevant sectors (ie, food security, agriculture, biodiversity, food processing, trade, and waste management, besides health and nutrition). The documents were selected purposively. The textual data were coded and compared, from which themes were identified, described, and interpreted. Additionally, mentions of various health concerns and of the health ministry in the included documents were recorded and collated.
RESULTS
A total of 35 policy documents were included in the analysis. A variety of health concerns spanning nutritional, communicable and non-communicable diseases (NCDs) were mentioned. Undernutrition received specific attention even beyond nutrition policies. Only few policies mentioned NCDs, infectious diseases, and injuries. Governing and advisory bodies were instituted by 17 of the analysed policies (eg, food safety, agriculture, and food processing), and often included representation from the health ministry (9 of the 17 identified inter-ministerial bodies).
CONCLUSION
We found some evidence of concern for health, and inclusion of health ministry in food policy documents in India. The ongoing and planned intersectoral coordination to tackle undernutrition could inform actions to address other relevant but currently underappreciated concerns such as NCDs. Our study demonstrated a method for analysis of health consideration and intersectoral coordination in food policy documents, which could be applied to studies in other settings and policy domains.
Topics: Humans; Health Policy; India; Malnutrition; Nutrition Policy; Nutritional Status; Policy Making
PubMed: 33904697
DOI: 10.34172/ijhpm.2021.18 -
Clinical Epigenetics Nov 2022DNA methylation is an important epigenetic mechanism that regulates gene expression. To date, most DNA methylation studies have focussed on CpG islands in the gene... (Review)
Review
DNA methylation is an important epigenetic mechanism that regulates gene expression. To date, most DNA methylation studies have focussed on CpG islands in the gene promoter region, and the mechanism of methylation and the regulation of gene expression after methylation have been clearly elucidated. However, genome-wide methylation studies have shown that DNA methylation is widespread not only in promoters but also in gene bodies. Gene body methylation is widely involved in the expression regulation of many genes and is closely related to the occurrence and progression of malignant tumours. This review focusses on the formation of gene body methylation patterns, its regulation of transcription, and its relationship with tumours, providing clues to explore the mechanism of gene body methylation in regulating gene transcription and its significance and application in the field of oncology.
Topics: Humans; DNA Methylation; Protein Processing, Post-Translational; Neoplasms; CpG Islands; Epigenesis, Genetic
PubMed: 36443876
DOI: 10.1186/s13148-022-01382-9 -
Signal Transduction and Targeted Therapy Apr 2024RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the...
RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.
Topics: Humans; Autophagy; Colorectal Neoplasms; Family; Phosphoproteins; Proteins; RNA; RNA, Circular; RNA-Binding Proteins
PubMed: 38565536
DOI: 10.1038/s41392-024-01787-3