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International Journal of Molecular... Jan 2018Auxin plays a crucial role in the diverse cellular and developmental responses of plants across their lifespan. Plants can quickly sense and respond to changes in auxin... (Review)
Review
Auxin plays a crucial role in the diverse cellular and developmental responses of plants across their lifespan. Plants can quickly sense and respond to changes in auxin levels, and these responses involve several major classes of auxin-responsive genes, including the () family, the () family, (), and the () family. Aux/IAA proteins are short-lived nuclear proteins comprising several highly conserved domains that are encoded by the auxin early response gene family. These proteins have specific domains that interact with ARFs and inhibit the transcription of genes activated by ARFs. Molecular studies have revealed that Aux/IAA family members can form diverse dimers with to regulate genes in various ways. Functional analyses of Aux/IAA family members have indicated that they have various roles in plant development, such as root development, shoot growth, and fruit ripening. In this review, recently discovered details regarding the molecular characteristics, regulation, and protein-protein interactions of the Aux/IAA proteins are discussed. These details provide new insights into the molecular basis of the Aux/IAA protein functions in plant developmental processes.
Topics: Gene Expression Regulation, Plant; Indoleacetic Acids; Multigene Family; Plant Development; Plant Proteins; Plants
PubMed: 29337875
DOI: 10.3390/ijms19010259 -
Nature Sep 2020Temperature controls plant growth and development, and climate change has already altered the phenology of wild plants and crops. However, the mechanisms by which plants...
Temperature controls plant growth and development, and climate change has already altered the phenology of wild plants and crops. However, the mechanisms by which plants sense temperature are not well understood. The evening complex is a major signalling hub and a core component of the plant circadian clock. The evening complex acts as a temperature-responsive transcriptional repressor, providing rhythmicity and temperature responsiveness to growth through unknown mechanisms. The evening complex consists of EARLY FLOWERING 3 (ELF3), a large scaffold protein and key component of temperature sensing; ELF4, a small α-helical protein; and LUX ARRYTHMO (LUX), a DNA-binding protein required to recruit the evening complex to transcriptional targets. ELF3 contains a polyglutamine (polyQ) repeat, embedded within a predicted prion domain (PrD). Here we find that the length of the polyQ repeat correlates with thermal responsiveness. We show that ELF3 proteins in plants from hotter climates, with no detectable PrD, are active at high temperatures, and lack thermal responsiveness. The temperature sensitivity of ELF3 is also modulated by the levels of ELF4, indicating that ELF4 can stabilize the function of ELF3. In both Arabidopsis and a heterologous system, ELF3 fused with green fluorescent protein forms speckles within minutes in response to higher temperatures, in a PrD-dependent manner. A purified fragment encompassing the ELF3 PrD reversibly forms liquid droplets in response to increasing temperatures in vitro, indicating that these properties reflect a direct biophysical response conferred by the PrD. The ability of temperature to rapidly shift ELF3 between active and inactive states via phase transition represents a previously unknown thermosensory mechanism.
Topics: Acclimatization; Arabidopsis; Arabidopsis Proteins; Hot Temperature; Models, Molecular; Peptides; Phase Transition; Prion Proteins; Protein Domains; Repressor Proteins; Temperature; Transcription Factors
PubMed: 32848244
DOI: 10.1038/s41586-020-2644-7 -
Cell Feb 2020Recognition of microbe-associated molecular patterns (MAMPs) is crucial for the plant's immune response. How this sophisticated perception system can be usefully...
Recognition of microbe-associated molecular patterns (MAMPs) is crucial for the plant's immune response. How this sophisticated perception system can be usefully deployed in roots, continuously exposed to microbes, remains a mystery. By analyzing MAMP receptor expression and response at cellular resolution in Arabidopsis, we observed that differentiated outer cell layers show low expression of pattern-recognition receptors (PRRs) and lack MAMP responsiveness. Yet, these cells can be gated to become responsive by neighbor cell damage. Laser ablation of small cell clusters strongly upregulates PRR expression in their vicinity, and elevated receptor expression is sufficient to induce responsiveness in non-responsive cells. Finally, localized damage also leads to immune responses to otherwise non-immunogenic, beneficial bacteria. Damage-gating is overridden by receptor overexpression, which antagonizes colonization. Our findings that cellular damage can "switch on" local immune responses helps to conceptualize how MAMP perception can be used despite the presence of microbial patterns in the soil.
Topics: Arabidopsis; Arabidopsis Proteins; Ascorbate Peroxidases; Flagellin; Gene Expression Regulation, Plant; Laser Therapy; Membrane Proteins; Microscopy, Confocal; Plant Diseases; Plant Roots; Protein Kinases; Receptors, Pattern Recognition; Signal Transduction; Time-Lapse Imaging
PubMed: 32032516
DOI: 10.1016/j.cell.2020.01.013 -
Gut Microbes 2022Studies of the gut-liver axis have enhanced our understanding of the pathophysiology of various liver diseases and the mechanisms underlying the regulation of the...
Studies of the gut-liver axis have enhanced our understanding of the pathophysiology of various liver diseases and the mechanisms underlying the regulation of the effectiveness of therapies. Radiotherapy (RT) is an important therapeutic option for patients with unresectable hepatocellular carcinoma (HCC). However, the role of the microbiome in regulating the response to RT remains unclear. The present study characterizes the gut microbiome of patients responsive or non-responsive to RT and investigates the molecular mechanisms underlying the differences in patient response. We collected fecal samples for 16S rRNA sequencing from a prospective longitudinal trial of 24 HCC patients receiving RT. We used fecal microbiota transplantation (FMT), flow cytometry, and transcriptome sequencing to explore the effects of dysbiosis on RT. We also examined the role of stimulator of interferon genes (STING) in RT-associated antitumor immune responses mediated by gut microbiota in STING- (Tmem173) and cGAS-knockout (Mb21d1) mouse models. We propose that primary resistance to RT could be attributed to the disruption of the gut microbiome. Mechanistically, gut microbiome dysbiosis impairs antitumor immune responses by suppressing antigen presentation and inhibiting effector T cell functions through the cGAS-STING-IFN-I pathway. Cyclic-di-AMP - an emerging second messenger of bacteria - may act as a STING agonist and is thus a potential target for the prediction and modulation of responses to RT in HCC patients. Our study highlights the therapeutic potential of modulating the gut microbiome in HCC patients receiving RT and provides a new strategy for the radiosensitization of liver cancer.
Topics: Animals; Carcinoma, Hepatocellular; Dysbiosis; Gastrointestinal Microbiome; Immunity; Liver Neoplasms; Mice; Nucleotidyltransferases; Prospective Studies; RNA, Ribosomal, 16S
PubMed: 36093568
DOI: 10.1080/19490976.2022.2119055 -
Vaccines Apr 2022Vaccination to prevent and even eliminate disease is amongst the greatest achievements of modern medicine. Opportunities remain in vaccine development to improve... (Review)
Review
Vaccination to prevent and even eliminate disease is amongst the greatest achievements of modern medicine. Opportunities remain in vaccine development to improve protection across the whole population. A next step in vaccine development is the detailed molecular characterization of individual humoral immune responses against a pathogen, especially the rapidly evolving pathogens. New technologies such as sequencing the immune repertoire in response to disease, immunogenomics/vaccinomics, particularly the individual HLA variants, and high-throughput epitope characterization offer new insights into disease protection. Here, we highlight the emerging technologies that could be used to identify variation within the human population, facilitate vaccine discovery, improve vaccine safety and efficacy, and identify mechanisms of generating immunological memory. In today's vaccine-hesitant climate, these techniques used individually or especially together have the potential to improve vaccine effectiveness and safety and thus vaccine uptake rates. We highlight the importance of using these techniques in combination to understand the humoral immune response as a whole after vaccination to move beyond neutralizing titers as the standard for immunogenicity and vaccine efficacy, especially in clinical trials.
PubMed: 35632439
DOI: 10.3390/vaccines10050683 -
Biomolecules Jan 2023Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone that assists in the maturation of many client proteins involved in cellular signal transduction.... (Review)
Review
Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone that assists in the maturation of many client proteins involved in cellular signal transduction. As a regulator of cellular signaling processes, it is vital for the maintenance of cellular proteostasis and adaptation to environmental stresses. Emerging research shows that Hsp90 function in an organism goes well beyond intracellular proteostasis. In metazoans, Hsp90, as an environmentally responsive chaperone, is involved in inter-tissue stress signaling responses that coordinate and safeguard cell nonautonomous proteostasis and organismal health. In this way, Hsp90 has the capacity to influence evolution and aging, and effect behavioral responses to facilitate tissue-defense systems that ensure organismal survival. In this review, I summarize the literature on the organismal roles of Hsp90 uncovered in multicellular organisms, from plants to invertebrates and mammals.
Topics: Humans; Animals; HSP90 Heat-Shock Proteins; Molecular Chaperones; Signal Transduction; Proteostasis; Stress, Physiological; Mammals
PubMed: 36830620
DOI: 10.3390/biom13020251 -
Genes & Genetic Systems Dec 2022Conifers are important in many forest ecosystems. They have a long generation time and are immobile; therefore, they require considerable plasticity to adapt to... (Review)
Review
Conifers are important in many forest ecosystems. They have a long generation time and are immobile; therefore, they require considerable plasticity to adapt to environmental stresses. Moreover, conifers have a large genome, a high proportion of which is occupied by repetitive elements. Retrotransposons are the most highly represented repetitive elements in conifers whose whole-genome sequences have been examined. These retrotransposons are usually silenced, to maintain genome integrity; however, some are activated by environmental stress. The insertion of retrotransposons into genic regions is associated with phenotypic and genetic diversity. The large number and high diversity of retrotransposons in conifer genomes suggest that they play a role in adaptation to the environment. In this review, progress in research on the roles of retrotransposons in the stress responses of conifers is reviewed, and potential future work is discussed.
Topics: Retroelements; Tracheophyta; Ecosystem; Terminal Repeat Sequences; Genome, Plant
PubMed: 36384751
DOI: 10.1266/ggs.22-00042 -
Research (Washington, D.C.) 2023Cancer immunotherapy has achieved tremendous successful clinical results and obtained historic victories in tumor treatments. However, great limitations associated with... (Review)
Review
Cancer immunotherapy has achieved tremendous successful clinical results and obtained historic victories in tumor treatments. However, great limitations associated with feeble immune responses and serious adverse effects still cannot be neglected due to the complicated multifactorial etiology and pathologic microenvironment in tumors. The rapid development of nanomedical science and material science has facilitated the advanced progress of engineering biomaterials to tackle critical issues. The supramolecular biomaterials with flexible and modular structures have exhibited unparalleled advantages of high cargo-loading efficiency, excellent biocompatibility, and diversiform immunomodulatory activity, thereby providing a powerful weapon for cancer immunotherapy. In past decades, supramolecular biomaterials were extensively explored as versatile delivery platforms for immunotherapeutic agents or designed to interact with the key moleculars in immune system in a precise and controllable manner. In this review, we focused on the crucial role of supramolecular biomaterials in the modulation of pivotal steps during tumor immunotherapy, including antigen delivery and presentation, T lymphocyte activation, tumor-associated macrophage elimination and repolarization, and myeloid-derived suppressor cell depletion. Based on extensive research, we explored the current limitations and development prospects of supramolecular biomaterials in cancer immunotherapy.
PubMed: 37705962
DOI: 10.34133/research.0211 -
ELife Jun 2023Bacterial pneumonia in neonates can cause significant morbidity and mortality when compared to other childhood age groups. To understand the immune mechanisms that...
Bacterial pneumonia in neonates can cause significant morbidity and mortality when compared to other childhood age groups. To understand the immune mechanisms that underlie these age-related differences, we employed a mouse model of pneumonia to determine the dynamic cellular and molecular differences in immune responsiveness between neonates (PND 3-5) and juveniles (PND 12-18), at 24, 48, and 72 hr. Cytokine gene expression from whole lung extracts was also quantified at these time points, using quantitative RT-PCR. challenge resulted in rapid and significant increases in neutrophils, monocytes, and γδT cells, along with significant decreases in dendritic cells and alveolar macrophages in the lungs of both neonates and juveniles. -challenged juvenile lung had significant increases in interstitial macrophages and recruited monocytes that were not observed in neonatal lungs. Expression of IFNγ-responsive genes was positively correlated with the levels and dynamics of MHCII-expressing innate cells in neonatal and juvenile lungs. Several facets of immune responsiveness in the wild-type neonates were recapitulated in juvenile juveniles. Employing a pre-clinical model of pneumonia, we identified significant differences in the early cellular and molecular dynamics in the lungs that likely contribute to the elevated susceptibility of neonates to bacterial pneumonia and could represent targets for intervention to improve respiratory outcomes and survivability of neonates.
Topics: Animals; Mice; Escherichia coli; Molecular Dynamics Simulation; Lung; Pneumonia, Bacterial; Cytokines; Escherichia coli Infections
PubMed: 37266566
DOI: 10.7554/eLife.82933 -
Chemical Reviews May 2024Since the last century, we have witnessed the development of molecular magnetism which deals with magnetic materials based on molecular species, i.e., organic radicals... (Review)
Review
Since the last century, we have witnessed the development of molecular magnetism which deals with magnetic materials based on molecular species, i.e., organic radicals and metal complexes. Among them, the broadest attention was devoted to molecule-based ferro-/ferrimagnets, spin transition materials, including those exploring electron transfer, molecular nanomagnets, such as single-molecule magnets (SMMs), molecular qubits, and stimuli-responsive magnetic materials. Their physical properties open the application horizons in sensors, data storage, spintronics, and quantum computation. It was found that various optical phenomena, such as thermochromism, photoswitching of magnetic and optical characteristics, luminescence, nonlinear optical and chiroptical effects, as well as optical responsivity to external stimuli, can be implemented into molecule-based magnetic materials. Moreover, the fruitful interactions of these optical effects with magnetism in molecule-based materials can provide new physical cross-effects and multifunctionality, enriching the applications in optical, electronic, and magnetic devices. This Review aims to show the scope of optical phenomena generated in molecule-based magnetic materials, including the recent advances in such areas as high-temperature photomagnetism, optical thermometry utilizing SMMs, optical addressability of molecular qubits, magneto-chiral dichroism, and opto-magneto-electric multifunctionality. These findings are discussed in the context of the types of optical phenomena accessible for various classes of molecule-based magnetic materials.
PubMed: 38687182
DOI: 10.1021/acs.chemrev.3c00840