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Frontiers in Plant Science 2022Plants balance water availability with gas exchange and photosynthesis by controlling stomatal aperture. This control is regulated in part by the circadian clock, but it...
Plants balance water availability with gas exchange and photosynthesis by controlling stomatal aperture. This control is regulated in part by the circadian clock, but it remains unclear how signalling pathways of daily rhythms are integrated into stress responses. The serine/threonine protein kinase OPEN STOMATA 1 (OST1) contributes to the regulation of stomatal closure activation of S-type anion channels. OST1 also mediates gene regulation in response to ABA/drought stress. We show that ZEITLUPE (ZTL), a blue light photoreceptor and clock component, also regulates ABA-induced stomatal closure in , establishing a link between clock and ABA-signalling pathways. ZTL sustains expression of and ABA-signalling genes. Stomatal closure in response to ABA is reduced in mutants, which maintain wider stomatal apertures and show higher rates of gas exchange and water loss than wild-type plants. Detached rosette leaf assays revealed a stronger water loss phenotype in , double mutants, indicating that ZTL and OST1 contributed synergistically to the control of stomatal aperture. Experimental studies of sp., revealed that ZTL regulated the circadian clock and stomata, indicating ZTL function was similar in these trees and Arabidopsis. PSEUDO-RESPONSE REGULATOR 5 (PRR5), a known target of ZTL, affects ABA-induced responses, including stomatal regulation. Like ZTL, PRR5 interacted physically with OST1 and contributed to the integration of ABA responses with circadian clock signalling. This suggests a novel mechanism whereby the PRR proteins-which are expressed from dawn to dusk-interact with OST1 to mediate ABA-dependent plant responses to reduce water loss in time of stress.
PubMed: 35310670
DOI: 10.3389/fpls.2022.829121 -
Plant Physiology Jun 2022Environmental signals, especially daylength, play important roles in determining fertility in photoperiod-sensitive genic male sterile (PGMS) lines that are critical to...
Environmental signals, especially daylength, play important roles in determining fertility in photoperiod-sensitive genic male sterile (PGMS) lines that are critical to sustain production of high-yielding hybrid rice (Oryza sativa) varieties. However, the mechanisms by which PGMS lines perceive changes in photoperiod and transmit those signals to elicit downstream effects are not well understood. In this study, we compared the transcriptomes from the leaves and anthers of carbon starved anther (csa), a PGMS line, to wild-type (WT) tissues under different photoperiods. Components of circadian clock in the leaves, including Circadian Clock-Associated 1 and Pseudo-Response Regulator (PRR95), played vital roles in sensing the photoperiod signals. Photoperiod signals were weakly transduced to anthers, where gene expression was mainly controlled by the CSA allele. CSA played a critical role in regulating sugar metabolism and cell wall synthesis in anthers under short-day conditions, and transcription of key genes inducing csa-directed sterility was upregulated under long-day (LD) conditions though not to WT levels, revealing a mechanism to explain the partial restoration of fertility in rice under LD conditions. Eight direct targets of CSA regulation were identified, all of which were genes involved in sugar metabolism and transport (cell wall invertases, SWEETs, and monosaccharide transporters) expressed only in reproductive tissues. Several hub genes coordinating the effects of CSA regulation were identified as critical elements determining WT male fertility and further analysis of these and related genes will reveal insights into how CSA coordinates sugar metabolism, cell wall biosynthesis, and photoperiod sensing in rice anther development.
Topics: Fertility; Gene Expression Regulation, Plant; Oryza; Photoperiod; Plant Proteins; Sugars
PubMed: 35274732
DOI: 10.1093/plphys/kiac076 -
Cancers Mar 2022Gliomas, and glioblastoma in particular, exhibit an extensive intra- and inter-tumoral molecular heterogeneity which represents complex biological features correlating... (Review)
Review
Gliomas, and glioblastoma in particular, exhibit an extensive intra- and inter-tumoral molecular heterogeneity which represents complex biological features correlating to the efficacy of treatment response and survival. From a neuroimaging point of view, these specific molecular and histopathological features may be used to yield imaging biomarkers as surrogates for distinct tumor genotypes and phenotypes. The development of comprehensive glioma imaging markers has potential for improved glioma characterization that would assist in the clinical work-up of preoperative treatment planning and treatment effect monitoring. In particular, the differentiation of tumor recurrence or true progression from pseudoprogression, pseudoresponse, and radiation-induced necrosis can still not reliably be made through standard neuroimaging only. Given the abundant vascular and hemodynamic alterations present in diffuse glioma, advanced hemodynamic imaging approaches constitute an attractive area of clinical imaging development. In this context, the inclusion of objective measurable glioma imaging features may have the potential to enhance the individualized care of diffuse glioma patients, better informing of standard-of-care treatment efficacy and of novel therapies, such as the immunotherapies that are currently increasingly investigated. In Part B of this two-review series, we assess the available evidence pertaining to hemodynamic imaging for molecular feature prediction, in particular focusing on isocitrate dehydrogenase (IDH) mutation status, MGMT promoter methylation, 1p19q codeletion, and EGFR alterations. The results for the differentiation of tumor progression/recurrence from treatment effects have also been the focus of active research and are presented together with the prognostic correlations identified by advanced hemodynamic imaging studies. Finally, the state-of-the-art concepts and advancements of hemodynamic imaging modalities are reviewed together with the advantages derived from the implementation of radiomics and machine learning analyses pipelines.
PubMed: 35267650
DOI: 10.3390/cancers14051342 -
Neuro-oncology Aug 2022Diffuse Midline Glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis.
BACKGROUND
Diffuse Midline Glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis.
METHODS
We conducted a multi-site Phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma (NCT03416530). Patients enrolled on Arm D of the trial (n = 24) underwent serial lumbar puncture for cell-free tumor DNA (cf-tDNA) analysis and patients on all arms at the University of Michigan underwent serial plasma collection. We performed digital droplet polymerase chain reaction (ddPCR) analysis of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal 2D tumor area on MRI).
RESULTS
Change in H3.3K27M VAF over time ("VAF delta") correlated with prolonged PFS in both CSF and plasma samples. Nonrecurrent patients that had a decrease in CSF VAF displayed a longer progression free survival (P = .0042). Decrease in plasma VAF displayed a similar trend (P = .085). VAF "spikes" (increase of at least 25%) preceded tumor progression in 8/16 cases (50%) in plasma and 5/11 cases (45.4%) in CSF. In individual cases, early reduction in H3K27M VAF predicted long-term clinical response (>1 year) to ONC201, and did not increase in cases of later-defined pseudo-progression.
CONCLUSION
Our work demonstrates the feasibility and potential utility of serial cf-tDNA in both plasma and CSF of DMG patients to supplement radiographic monitoring. Patterns of change in H3K27M VAF over time demonstrate clinical utility in terms of predicting progression and sustained response and possible differentiation of pseudo-progression and pseudo-response.
Topics: Brain Neoplasms; Child; Circulating Tumor DNA; Glioma; Histones; Humans; Imidazoles; Mutation; Pyridines; Pyrimidines
PubMed: 35137228
DOI: 10.1093/neuonc/noac030 -
TAG. Theoretical and Applied Genetics.... Jan 2022Gene distributions and population genomics suggest artificial selection of ghd7 osprr37, for extremely early heading date of rice, in the Tohoku region of Japan. The...
Gene distributions and population genomics suggest artificial selection of ghd7 osprr37, for extremely early heading date of rice, in the Tohoku region of Japan. The ranges of cultivated crops expanded into various environmental conditions around the world after their domestication. Hokkaido, Japan, lies at the northern limit of cultivation of rice, which originated in the tropics. Novel genotypes for extremely early heading date in Hokkaido are controlled by loss-of-function of both Grain number, plant height and heading date 7 (Ghd7) and Oryza sativa Pseudo-Response Regulator 37 (OsPRR37). We traced genotypes for extremely early heading date and analyzed the phylogeny of rice varieties grown historically in Japan. The mutations in Ghd7 and OsPRR37 had distinct local distributions. Population genomics revealed that varieties collected from the Tohoku region of northern Japan formed three clusters. Mutant alleles of Ghd7 and OsPRR37 appear to have allowed rice cultivation to spread into Hokkaido. Our results show that the mutations of two genes might be occurred in the process of artificial selection during early rice cultivation in the Tohoku region.
Topics: Genes, Plant; Genotype; Mutation; Oryza; Phylogeny; Plant Breeding; Selection, Genetic
PubMed: 34731272
DOI: 10.1007/s00122-021-03966-0 -
Frontiers in Plant Science 2021Peel color is an important factor affecting commodity quality in vegetables; however, the genes controlling this trait remain unclear in wax gourd. Here, we used two F...
Peel color is an important factor affecting commodity quality in vegetables; however, the genes controlling this trait remain unclear in wax gourd. Here, we used two F genetic segregation populations to explore the inheritance patterns and to clone the genes associated with green and white skin in wax gourd. The F and BC trait segregation ratios were 3:1 and 1:1, respectively, and the trait was controlled by nuclear genes. Bulked segregant analysis of both F plants revealed peaks on Chr5 exceeding the confidence interval. Additionally, 6,244 F plants were used to compress the candidate interval into a region of 179 Kb; one candidate gene, (), encoding two-component response regulator-like protein pseudo-response regulator2 (APRR2), which is involved in the regulation of peel color, was present in this interval. Two bases (GA) present in the coding sequence of in green-skinned wax gourd were absent from white-skinned wax gourd. The latter contained a frameshift mutation, a premature stop codon, and lacked 335 residues required for the protein functional region. The chlorophyll content and expression were significantly higher in green-skinned than in white-skinned wax gourd. Thus, may regulate the peel color of wax gourd. This study provides a theoretical foundation for further studies of the mechanism of gene regulation for the fruit peel color of wax gourd.
PubMed: 34659288
DOI: 10.3389/fpls.2021.716772 -
Clinical Case Reports Aug 2021Antiangiogenic agents can induce a distinct MRI pattern in glioblastoma, characterized by a decrease in the contrast enhancement on T1-weighted images and a simultaneous...
Antiangiogenic agents can induce a distinct MRI pattern in glioblastoma, characterized by a decrease in the contrast enhancement on T1-weighted images and a simultaneous hyperintensity on T2-weighted or fluid-attenuated inversion recovery images.
PubMed: 34457284
DOI: 10.1002/ccr3.4604 -
Frontiers in Plant Science 2021Photoperiod-regulated floral transition is vital to the flowering plant. "Xiangfei" is a flowering ornamental plant with high development potential economically and is...
Photoperiod-regulated floral transition is vital to the flowering plant. "Xiangfei" is a flowering ornamental plant with high development potential economically and is a short-day woody perennial. However, the genetic regulation of short-day-induced floral transition in is unclear. To systematically research the responses of during this process, dynamic changes in morphology, physiology, and transcript levels were observed and identified in different developmental stages of long-day- and short-day-treated plants. We found that floral transition in occurred 10 d after short-day induction, but flower bud differentiation did not occur at any stage under long-day conditions. A total of 1,226 differentially expressed genes were identified, of which 146 genes were associated with flowering pathways of sugar, phytohormones, photoperiod, ambient temperature, and aging signals, as well as floral integrator and meristem identity genes. The trehalose-6-phosphate signal positively modulated floral transition by interacting with SQUAMOSA PROMOTER-BINDING-LIKE PROTEIN 4 (SPL4) in the aging pathway. Endogenous gibberellin, abscisic acid, cytokinin, and jasmonic acid promoted floral transition, whereas strigolactone inhibited it. In the photoperiod pathway, FD, CONSTANS-LIKE 12, and nuclear factors Y positively controlled floral transition, whereas PSEUDO-RESPONSE REGULATOR 7, FLAVIN-BINDING KELCH REPEAT F-BOX PROTEIN 1, and LUX negatively regulated it. SPL4 and pEARLI1 positively affected floral transition. Suppressor of Overexpression of Constans 1 and AGAMOUSLIKE24 integrated multiple flowering signals to modulate the expression of /, , , , , and , thereby regulating floral transition. Finally, we propose a regulatory network model for short-day-induced floral transition in . This study improves our understanding of flowering time regulation in and provides knowledge for its production and commercialization.
PubMed: 34456954
DOI: 10.3389/fpls.2021.715683 -
Neuro-oncology Advances 2021Currently, bevacizumab (BEV), an antiangiogenic agent, is used as an adjunctive therapy to re-irradiation and surgery in patients with recurrent high-grade gliomas... (Review)
Review
BACKGROUND
Currently, bevacizumab (BEV), an antiangiogenic agent, is used as an adjunctive therapy to re-irradiation and surgery in patients with recurrent high-grade gliomas (rHGG). BEV has shown to decrease enhancement on MRI, but it is often unclear if these changes are due to tumor response to BEV or treatment-induced changes in the blood brain barrier. Preliminary studies show that amino acid PET can aid in distinguishing these changes on MRI.
METHODS
The authors performed a systematic review of PubMed and Embase through July 2020 with the search terms 'bevacizumab' or 'Avastin' and 'recurrent glioma' and 'PET,' yielding 38 papers, with 14 meeting inclusion criteria.
RESULTS
Thirteen out of fourteen studies included in this review used static PET and three studies used dynamic PET to evaluate the use of BEV in rHGG. Six studies used the amino acid tracer [18F]FET, four studies used [11C]MET, and four studies used [18F]FDOPA.
CONCLUSION
[18F]FET, [11C]MET, and [18F]FDOPA PET in combination with MRI have shown promising results for improving accuracy in diagnosing tumor recurrence, detecting early treatment failure, and distinguishing between tumor progression and treatment-induced changes in patients with rHGG treated with BEV.
PubMed: 34409294
DOI: 10.1093/noajnl/vdab003 -
Statistics in Medicine Oct 2021Observational studies usually include participants representing the wide heterogeneous population. The conditional causal effect, treatment effect conditional on...
Observational studies usually include participants representing the wide heterogeneous population. The conditional causal effect, treatment effect conditional on baseline characteristics, is of practical importance. Its estimation is subject to two challenges. First, the causal effect is not observable in any individual due to counterfactuality. Second, high-dimensional baseline variables are involved to satisfy the ignorable treatment selection assumption and to attain better estimation efficiency. In this work, a nonparametric estimation procedure, along with a pseudo-response, is proposed to estimate the conditional treatment effect through "characteristic score"-a parsimonious representation of baseline variable influence on treatment benefit. Adopting sparse dimension reduction with variable prescreening in the proposed estimation, we aim to identify the key baseline variables that impact the conditional treatment effect and to uncover the characteristic score that best predicts the treatment effect. This approach is applied to an HIV study for assessing the benefit of antiretroviral regimens and identifying the beneficiary subpopulation.
Topics: Causality; Humans
PubMed: 34181277
DOI: 10.1002/sim.9119