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Frontiers in Plant Science 2023NAC transcription factors are an important genes that regulate plant growth and development, and can regulate functions such as fruit ripening in plants. Based on genome...
NAC transcription factors are an important genes that regulate plant growth and development, and can regulate functions such as fruit ripening in plants. Based on genome data of , the gene family was identified and analyzed by bioinformatics methods. In this study, we identified 85 genes in genome, and systematically analyzed the gene family. We found that they were distributed unevenly in the nineteen chromosomes. The amino acid length of gene family () ranged from 80 to 1065, molecular weight ranged from 22.17 to 119.02 kD, and isoelectric point ranged from 4.61~9.26. Its promoter region contains multiple stress responsive elements, including light responsive, gibberellin-responsive, abscisic acid responsiveness, MeJA-responsiveness and drought-inducibility elements. Phylogenetic analysis indicates that the gene family is most closely related to and . Analysis of SSR loci indicates that the fraction of mononucleotide repeats was the largest, as was the frequency of A/T. Non-coding RNA analysis showed that these 85 genes contain 397 miRNAs. The collinearity analysis shows that 9 collinear locis were found on the chromosomes of with , and 75 collinear locis with QRT-PCR experiment under different salt concentration and temperature conditions verified the response mechanism of gene family under stress conditions. Most genes are sensitive to salt stress and temperature stress. The results of this study provide a reference for further understanding the function of gene in .
PubMed: 37670854
DOI: 10.3389/fpls.2023.1232804 -
Exploration (Beijing, China) Jun 2023The acidic characteristic of the tumor site is one of the most well-known features and provides a series of opportunities for cancer-specific theranostic strategies. In... (Review)
Review
The acidic characteristic of the tumor site is one of the most well-known features and provides a series of opportunities for cancer-specific theranostic strategies. In this regard, pH-responsive theranostic nanoplatforms that integrate diagnostic and therapeutic capabilities are highly developed. The fluidity of the tumor microenvironment (TME), with its temporal and spatial heterogeneities, makes noninvasive molecular magnetic resonance imaging (MRI) technology very desirable for imaging TME constituents and developing MRI-guided theranostic nanoplatforms for tumor-specific treatments. Therefore, various MRI-based theranostic strategies which employ assorted therapeutic modes have been drawn up for more efficient cancer therapy through the raised local concentration of therapeutic agents in pathological tissues. In this review, we summarize the pH-responsive mechanisms of organic components (including polymers, biological molecules, and organosilicas) as well as inorganic components (including metal coordination compounds, metal oxides, and metal salts) of theranostic nanoplatforms. Furthermore, we review the designs and applications of pH-responsive theranostic nanoplatforms for the diagnosis and treatment of cancer. In addition, the challenges and prospects in developing theranostic nanoplatforms with pH-responsiveness for cancer diagnosis and therapy are discussed.
PubMed: 37933379
DOI: 10.1002/EXP.20220002 -
Molecular Cancer Therapeutics Mar 2022Targeting the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway with immunotherapy has revolutionized the treatment of many cancers. Somatic tumor...
Targeting the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway with immunotherapy has revolutionized the treatment of many cancers. Somatic tumor mutational burden (TMB) and T-cell-inflamed gene expression profile (GEP) are clinically validated pan-tumor genomic biomarkers that can predict responsiveness to anti-PD-1/PD-L1 monotherapy in many tumor types. We analyzed the association between these biomarkers and the efficacy of PD-1 inhibitor in 11 commonly used preclinical syngeneic tumor mouse models using murinized rat anti-mouse PD-1 DX400 antibody muDX400, a surrogate for pembrolizumab. Response to muDX400 treatment was broadly classified into three categories: highly responsive, partially responsive, and intrinsically resistant to therapy. Molecular and cellular profiling validated differences in immune cell infiltration and activation in the tumor microenvironment of muDX400-responsive tumors. Baseline and on-treatment genomic analysis showed an association between TMB, murine T-cell-inflamed gene expression profile (murine-GEP), and response to muDX400 treatment. We extended our analysis to investigate a canonical set of cancer and immune biology-related gene signatures, including signatures of angiogenesis, myeloid-derived suppressor cells, and stromal/epithelial-to-mesenchymal transition/TGFβ biology previously shown to be inversely associated with the clinical efficacy of immune checkpoint blockade. Finally, we evaluated the association between murine-GEP and preclinical efficacy with standard-of-care chemotherapy or antiangiogenic agents that previously demonstrated promising clinical activity, in combination with muDX400. Our profiling studies begin to elucidate the underlying biological mechanisms of response and resistance to PD-1/PD-L1 blockade represented by these models, thereby providing insight into which models are most appropriate for the evaluation of orthogonal combination strategies.
Topics: Animals; B7-H1 Antigen; Biomarkers, Tumor; Cell Line, Tumor; Disease Models, Animal; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Mice; Neoplasms; Programmed Cell Death 1 Receptor; Tumor Microenvironment
PubMed: 34965960
DOI: 10.1158/1535-7163.MCT-21-0561 -
Proceedings of the National Academy of... Mar 2021Polyploidy is a prominent feature for genome evolution in many animals and all flowering plants. Plant polyploids often show enhanced fitness in diverse and extreme...
Polyploidy is a prominent feature for genome evolution in many animals and all flowering plants. Plant polyploids often show enhanced fitness in diverse and extreme environments, but the molecular basis for this remains elusive. Soil salinity presents challenges for many plants including agricultural crops. Here we report that salt tolerance is enhanced in tetraploid rice through lower sodium uptake and correlates with epigenetic regulation of jasmonic acid (JA)-related genes. Polyploidy induces DNA hypomethylation and potentiates genomic loci coexistent with many stress-responsive genes, which are generally associated with proximal transposable elements (TEs). Under salt stress, the stress-responsive genes including those in the JA pathway are more rapidly induced and expressed at higher levels in tetraploid than in diploid rice, which is concurrent with increased jasmonoyl isoleucine (JA-Ile) content and JA signaling to confer stress tolerance. After stress, elevated expression of stress-responsive genes in tetraploid rice can induce hypermethylation and suppression of the TEs adjacent to stress-responsive genes. These induced responses are reproducible in a recurring round of salt stress and shared between two tetraploid rice lines. The data collectively suggest a feedback relationship between polyploidy-induced hypomethylation in rapid and strong stress response and stress-induced hypermethylation to repress proximal TEs and/or TE-associated stress-responsive genes. This feedback regulation may provide a molecular basis for selection to enhance adaptation of polyploid plants and crops during evolution and domestication.
Topics: Cyclopentanes; DNA Methylation; DNA Transposable Elements; Epigenesis, Genetic; Gene Expression Regulation, Plant; Isoleucine; Oryza; Oxylipins; Salt Tolerance; Tetraploidy
PubMed: 33771925
DOI: 10.1073/pnas.2023981118 -
Frontiers in Immunology 2023Natural Killer (NK) cells contribute to the protective effects of vaccine-induced antibodies thanks to the low affinity receptor for IgG, FcγRIIIA/CD16, whose...
INTRODUCTION
Natural Killer (NK) cells contribute to the protective effects of vaccine-induced antibodies thanks to the low affinity receptor for IgG, FcγRIIIA/CD16, whose aggregation leads to the killing of infected cells and IFNγ release, through which they potentiate adaptive immune responses.
METHODS
Forty-seven healthy young individuals undergoing either homologous (ChAdOx1-S/ChAdOx1-S) or heterologous (ChAdOx1-S/BNT162B2) SARS-CoV-2 vaccination settings were recruited. Peripheral blood samples were collected immediately prior to vaccination and 8 weeks after the booster dose. The phenotypic and functional profile of NK cells was evaluated by flow cytometry at both time points. Serum samples were tested to evaluate circulating anti-Spike IgG levels and cytomegalovirus serostatus. CD16 F158V polymorphism was assessed by sequencing analysis.
RESULTS
The downregulation of CD16 and the selective impairment of antibody-dependent cytotoxicity and IFNγ production in CD56 NK population, persisting 8 weeks after boosting, were observed in heterologous, but not in homologous SARS-CoV-2 vaccination scheme. While the magnitude of CD16-dependent functions of the global CD56 pool correlated with receptor levels before and after vaccination, the responsivity of NKG2C subset, that displays amplified size and functionality in HCMV individuals, resulted intrinsically insensitive to CD16 levels. Individual CD16 responsiveness was also affected by CD16F158V polymorphism; F/F low affinity individuals, characterized by reduced CD16 levels and functions independently of vaccination, did not show post-vaccinal functional impairment with respect to intermediate and high affinity ones, despite a comparable CD16 downregulation. Further, CD16 high affinity ligation conditions by means of afucosylated mAb overcame vaccine-induced and genotype-dependent functional defects. Finally, the preservation of CD16 expression directly correlated with anti-Spike IgG titer, hinting that the individual magnitude of receptor-dependent functions may contribute to the amplification of the vaccinal response.
CONCLUSION
This study demonstrates a durable downmodulation of CD16 levels and Ab-dependent NK functions after SARS-CoV-2 heterologous vaccination, and highlights the impact of genetic and environmental host-related factors in modulating NK cell susceptibility to post-vaccinal Fc-dependent functional impairment.
Topics: Humans; COVID-19 Vaccines; SARS-CoV-2; Antibody-Dependent Cell Cytotoxicity; BNT162 Vaccine; COVID-19; Killer Cells, Natural; Antibodies, Viral; Vaccination; Immunoglobulin G
PubMed: 38045702
DOI: 10.3389/fimmu.2023.1285203 -
ACS Bio & Med Chem Au Aug 2022Recent work has proposed a new mechanism of bacterial iron regulation: riboswitches that undergo a conformational change in response to Fe. The (NiCo) riboswitch was...
Recent work has proposed a new mechanism of bacterial iron regulation: riboswitches that undergo a conformational change in response to Fe. The (NiCo) riboswitch was initially proposed to be specific for Ni and Co, but we recently showed via a -based fluorescent sensor that Fe is also a plausible physiological ligand for this riboswitch class. Here, we provide direct evidence that this riboswitch class responds to Fe. Isothermal titration calorimetry studies of the native riboswitches from three organisms show no response to Mn, a weak response to Zn, and similar dissociation constants (∼1 μM) and conformational responses for Fe, Co, and Ni. Only the iron response is in the physiological concentration regime; the riboswitches' responses to Co, Ni, and Zn require 10-, 10-, and 10-fold higher "free" metal ion concentrations, respectively, than the typical availability of those metal ions in cells. By contrast, the "Sensei" RNA, recently claimed to be an iron-specific riboswitch, exhibits no response to Fe. Our results demonstrate that iron responsiveness is a conserved property of riboswitches and clarify that this is the only family of iron-responsive riboswitch identified to date, setting the stage for characterization of their physiological function.
PubMed: 35996475
DOI: 10.1021/acsbiomedchemau.1c00069 -
Open Biology Apr 2018The endoplasmic reticulum (ER) stress response is regarded as an important process in the aetiology of Alzheimer's disease (AD). The accumulation of pathogenic misfolded... (Review)
Review
The endoplasmic reticulum (ER) stress response is regarded as an important process in the aetiology of Alzheimer's disease (AD). The accumulation of pathogenic misfolded proteins and the disruption of intracellular calcium (Ca) signalling are considered to be fundamental mechanisms that underlie the induction of ER stress, leading to neuronal cell death. Indeed, a number of studies have proposed molecular mechanisms linking ER stress to AD pathogenesis based on results from systems and AD mouse models. However, stress responsivity was largely different between each mouse model, even though all of these models display AD-related pathologies. While several reports have shown elevated ER stress responses in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (Tg) AD mouse models, we and other groups, in contrast, observed no such ER stress response in APP-single-Tg or -knockin mice. Therefore, it is debatable whether the ER stress observed in APP and PS1 double-Tg mice is due to AD pathology. From these findings, the roles of ER stress in AD pathogenesis needs to be carefully addressed in future studies. In this review, we summarize research detailing the relationship between ER stress and AD, and analyse the results in detail.
Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Calcium Signaling; Endoplasmic Reticulum Stress; Mice; Mice, Transgenic; Models, Molecular; Protein Folding
PubMed: 29695619
DOI: 10.1098/rsob.180024 -
Frontiers in Chemistry 2021Modulating the stimulus-responsiveness of a luminescent crystal is challenging owing to the complex interdependent nature of its controlling factors, such as molecular...
Modulating the stimulus-responsiveness of a luminescent crystal is challenging owing to the complex interdependent nature of its controlling factors, such as molecular structure, molecular conformation, crystal packing, optical properties, and amorphization behavior. Herein, we demonstrate a halogen-exchange approach that disentangles this problem, thereby realizing the modulation of room-temperature phosphorescence-to-phosphorescence mechanochromism. Replacing the bromine atoms in a brominated thienyl diketone with chlorine atoms afforded isostructural crystals; i.e., molecules with different halogen atoms exhibited the same molecular conformation and crystal packing. Consequently, amorphization behavior toward mechanical stimulation was also the same, and the phosphorescence of amorphous states originated from the same conformer of each diketone. In contrast, the phosphorescence properties of each conformer were modulated differently, which is ascribable to heavy atom effects, resulting in the modulation of the mechanochromism. Thus, halogen exchange is a promising approach for modulating the stimulus-responsive photofunctions of crystals involving spin-forbidden processes.
PubMed: 35096775
DOI: 10.3389/fchem.2021.812593 -
Leukemia Jan 2024Patients with multiple myeloma (MM) routinely receive mRNA-based vaccines to reduce COVID-19-related mortality. However, whether disease- and therapy-related alterations...
Patients with multiple myeloma (MM) routinely receive mRNA-based vaccines to reduce COVID-19-related mortality. However, whether disease- and therapy-related alterations in immune cells and cytokine-responsiveness contribute to the observed heterogeneous vaccination responses is unclear. Thus, we analyzed peripheral blood mononuclear cells from patients with MM during and after SARS-CoV-2 vaccination and breakthrough infection (BTI) using combined whole-transcriptome and surface proteome single-cell profiling with functional serological and T-cell validation in 58 MM patients. Our results demonstrate that vaccine-responders showed a significant overrepresentation of cytotoxic CD4 T- and mature CD38 NK-cells expressing FAS/TIM3 with a robust cytokine-responsiveness, such as type-I-interferon-, IL-12- and TNF-α-mediated signaling. Patients with MM experiencing BTI developed strong serological and cellular responses and exhibited similar cytokine-responsive immune cell patterns as vaccine-responders. This study can expand our understanding of molecular and cellular patterns associated with immunization responses and may benefit the design of improved vaccination strategies in immunocompromised patients.
Topics: Humans; COVID-19 Vaccines; Cytokines; Leukocytes, Mononuclear; Multiple Myeloma; COVID-19; SARS-CoV-2; Vaccination
PubMed: 38049509
DOI: 10.1038/s41375-023-02070-0 -
BMC Genomics May 2020Animals have specific molecular, physiological, and behavioral responses to light that are influenced by wavelength and intensity. Predictable environmental changes -...
BACKGROUND
Animals have specific molecular, physiological, and behavioral responses to light that are influenced by wavelength and intensity. Predictable environmental changes - predominantly solar and lunar cycles - drive endogenous daily oscillations by setting internal pacemakers, otherwise known as the circadian clock. Cnidarians have been a focal group to discern the evolution of light responsiveness due to their phylogenetic position as a sister phylum to bilaterians and broad range of light-responsive behaviors and physiology. Marine species that occupy a range of depths will experience different ranges of wavelengths and light intensities, which may result in variable phenotypic responses. Here, we utilize the eyeless sea anemone Nematostella vectensis, an estuarine anemone that typically resides in shallow water habitats, to compare behavioral and molecular responses when exposed to different light conditions.
RESULTS
Quantitative measures of locomotion clearly showed that this species responds to light in the blue and green spectral range with a circadian activity profile, in contrast to a circatidal activity profile in the red spectral range and in constant darkness. Differences in average day/night locomotion was significant in each condition, with overall peak activity during the dark period. Comparative analyses of 96 transcriptomes from individuals sampled every 4 h in each lighting treatment revealed complex differences in gene expression between colors, including in many of the genes likely involved in the cnidarian circadian clock. Transcriptional profiling showed the majority of genes are differentially expressed when comparing mid-day with mid-night, and mostly in red light. Gene expression profiles were largely unique in each color, although animals in blue and green were overall more similar to each other than to red light.
CONCLUSIONS
Together, these analyses support the hypothesis that cnidarians are sensitive to red light, and this perception results in a rich transcriptional and divergent behavioral response. Future work determining the specific molecular mechanisms driving the circadian and potential circatidal rhythms measured here would be impactful to connect gene expression variation with behavioral variation in this eyeless species.
Topics: Animals; Circadian Clocks; Circadian Rhythm Signaling Peptides and Proteins; Color; Darkness; Female; Gene Expression Regulation; Locomotion; Photoperiod; Pigments, Biological; Sea Anemones; Transcriptome
PubMed: 32410571
DOI: 10.1186/s12864-020-6766-y