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Magnetic Resonance Imaging Clinics of... Feb 2024Accurate diagnosis and treatment evaluation of patients with gliomas is imperative to make clinical decisions. Multiparametric MR perfusion imaging reveals physiologic... (Review)
Review
Accurate diagnosis and treatment evaluation of patients with gliomas is imperative to make clinical decisions. Multiparametric MR perfusion imaging reveals physiologic features of gliomas that can help classify them according to their histologic and molecular features as well as distinguish them from other neoplastic and nonneoplastic entities. It is also helpful in distinguishing tumor recurrence or progression from radiation necrosis, pseudoprogression, and pseudoresponse, which is difficult with conventional MR imaging. This review provides an update on MR perfusion imaging for the diagnosis and treatment monitoring of patients with gliomas following standard-of-care chemoradiation therapy and other treatment regimens such as immunotherapy.
Topics: Humans; Magnetic Resonance Imaging; Brain Neoplasms; Contrast Media; Glioma; Perfusion Imaging
PubMed: 38007284
DOI: 10.1016/j.mric.2023.07.003 -
Cancers Aug 2023Glioblastoma (GB) is a malignant brain tumour that is challenging to treat, often relapsing even after aggressive therapy. Evaluating therapy response relies on magnetic...
BACKGROUND
Glioblastoma (GB) is a malignant brain tumour that is challenging to treat, often relapsing even after aggressive therapy. Evaluating therapy response relies on magnetic resonance imaging (MRI) following the Response Assessment in Neuro-Oncology (RANO) criteria. However, early assessment is hindered by phenomena such as pseudoprogression and pseudoresponse. Magnetic resonance spectroscopy (MRS/MRSI) provides metabolomics information but is underutilised due to a lack of familiarity and standardisation.
METHODS
This study explores the potential of spectroscopic imaging (MRSI) in combination with several machine learning approaches, including one-dimensional convolutional neural networks (1D-CNNs), to improve therapy response assessment. Preclinical GB (GL261-bearing mice) were studied for method optimisation and validation.
RESULTS
The proposed 1D-CNN models successfully identify different regions of tumours sampled by MRSI, i.e., normal brain (N), control/unresponsive tumour (T), and tumour responding to treatment (R). Class activation maps using Grad-CAM enabled the study of the key areas relevant to the models, providing model explainability. The generated colour-coded maps showing the N, T and R regions were highly accurate (according to Dice scores) when compared against ground truth and outperformed our previous method.
CONCLUSIONS
The proposed methodology may provide new and better opportunities for therapy response assessment, potentially providing earlier hints of tumour relapsing stages.
PubMed: 37568818
DOI: 10.3390/cancers15154002 -
Current Oncology (Toronto, Ont.) Aug 2023Gliomas are the most frequent intrinsic central nervous system tumors. The new 2021 WHO Classification of Central Nervous System Tumors brought significant changes into... (Review)
Review
Gliomas are the most frequent intrinsic central nervous system tumors. The new 2021 WHO Classification of Central Nervous System Tumors brought significant changes into the classification of gliomas, that underline the role of molecular diagnostics, with the adult-type diffuse glial tumors now identified primarily by their biomarkers rather than histology. The status of the isocitrate dehydrogenase (IDH) 1 or 2 describes tumors at their molecular level and together with the presence or absence of 1p/19q codeletion are the most important biomarkers used for the classification of adult-type diffuse glial tumors. In recent years terminology has also changed. IDH-mutant, as previously known, is diagnostically used as astrocytoma and IDH-wildtype is used as glioblastoma. A comprehensive understanding of these tumors not only gives patients a more proper treatment and better prognosis but also highlights new difficulties. MR imaging is of the utmost importance for diagnosing and supervising the response to treatment. By monitoring the tumor on followup exams better results can be achieved. Correlations are seen between tumor diagnostic and clinical manifestation and surgical administration, followup care, oncologic treatment, and outcomes. Minimal resection site use of functional imaging (fMRI) and diffusion tensor imaging (DTI) have become indispensable tools in invasive treatment. Perfusion imaging provides insightful information about the vascularity of the tumor, spectroscopy shows metabolic activity, and nuclear medicine imaging displays tumor metabolism. To accommodate better treatment the differentiation of pseudoprogression, pseudoresponse, or radiation necrosis is needed. In this report, we present a literature review of diagnostics of gliomas, the differences in their imaging features, and our radiology's departments accumulated experience concerning gliomas.
Topics: Humans; Adult; Brain Neoplasms; Diffusion Tensor Imaging; Mutation; Glioma; Biomarkers
PubMed: 37754483
DOI: 10.3390/curroncol30090568 -
International Journal of Molecular... Jan 2024Plants monitor day length and memorize changes in temperature signals throughout the day, creating circadian rhythms that support the timely control of physiological and... (Review)
Review
Plants monitor day length and memorize changes in temperature signals throughout the day, creating circadian rhythms that support the timely control of physiological and metabolic processes. The () transcription factors are known as master regulators for the acquisition of cold stress tolerance, whereas () is involved in plant adaptation to heat stress through thermomorphogenesis. Recent studies have shown that circadian clock genes control plant responses to temperature. Temperature-responsive transcriptomes show a diurnal cycle and peak expression levels at specific times of throughout the day. Circadian clock genes play essential roles in allowing plants to maintain homeostasis by accommodating temperature changes within the normal temperature range or by altering protein properties and morphogenesis at the cellular level for plant survival and growth under temperature stress conditions. Recent studies revealed that the central oscillator genes / () and // (//), as well as the () genes (/), were involved in the pathway of the cold signaling transcription factor and regulated the thermomorphogenesis gene . Further studies showed that another central oscillator, (), and the regulatory protein () are also involved. These studies led to attempts to utilize circadian clock genes for the acquisition of temperature-stress resistance in crops. In this review, we highlight circadian rhythm regulation and the clock genes involved in plant responses to temperature changes, as well as strategies for plant survival in a rapidly changing global climate.
Topics: Temperature; Circadian Clocks; Cold Temperature; Circadian Rhythm; Climate
PubMed: 38255990
DOI: 10.3390/ijms25020918 -
TAG. Theoretical and Applied Genetics.... Oct 2023We clarify the influence of the genotypes of the heading date genes Hd1, Ghd7, DTH8, and PRR37 and their combinations on yield-related traits and the functional...
We clarify the influence of the genotypes of the heading date genes Hd1, Ghd7, DTH8, and PRR37 and their combinations on yield-related traits and the functional differences between different haplotypes. Heading date is a key agronomic trait in rice (Oryza sativa L.) that determines yield and adaptability to different latitudes. Heading date 1 (Hd1), Grain number, plant height, and heading date 7 (Ghd7), Days to heading on chromosome 8 (DTH8), and PSEUDO-RESPONSE REGULATOR 37 (PRR37) are core rice genes controlling photoperiod sensitivity, and these genes have many haplotypes in rice cultivars. However, the effects of different haplotypes at these genes on yield-related traits in diverse rice materials remain poorly characterized. In this study, we knocked out Hd1, Ghd7, DTH8, or PRR37, alone or together, in indica and japonica varieties and systematically investigated the agronomic traits of each knockout line. Ghd7 and PRR37 increased the number of spikelets and improved yield, and this effect was enhanced with the Ghd7 DTH8 or Ghd7 PRR37 combination, but Hd1 negatively affected yield. We also identified a new weak functional Ghd7 allele containing a mutation that interferes with splicing. Furthermore, we determined that the promotion or inhibition of heading date by different PRR37 haplotypes is related to PRR37 expression levels, day length, and the genetic background. For rice breeding, a combination of functional alleles of Ghd7 and DTH8 or Ghd7 and PRR37 in the hd1 background can be used to increase yield. Our study clarifies the effects of heading date genes on yield-related traits and the functional differences among their different haplotypes, providing valuable information to identify and exploit elite haplotypes for heading date genes to breed high-yielding rice varieties.
Topics: Oryza; Plant Breeding; Phenotype; Mutation; Genotype; Plant Proteins; Gene Expression Regulation, Plant; Flowers; Photoperiod
PubMed: 37851149
DOI: 10.1007/s00122-023-04476-x -
Plant, Cell & Environment Sep 2023As an endogenous time-keeping mechanism, the circadian clock benefits plant fitness and adaptation to the rhythmically changed diel environments. The key components...
As an endogenous time-keeping mechanism, the circadian clock benefits plant fitness and adaptation to the rhythmically changed diel environments. The key components within the core oscillator of plant circadian clock have been extensively characterised, however, the fine-tuning circadian regulators are still less identified. Here, we demonstrated that BBX28 and BBX29, the two B-Box V subfamily members lacking DNA-binding motifs, are involved in the regulation of Arabidopsis circadian clock. Over-expressing either BBX28 or BBX29 significantly lengthened circadian period, whereas loss-of-function of BBX28 rather than BBX29 displayed a modestly long period in free-running condition. Mechanistically, BBX28 and BBX29 interacted with core clock components PRR5, PRR7 and PRR9 in nucleus to augment their transcriptional repressive activities. RNA-sequencing analysis further revealed that BBX28 and BBX29 shared 686 common differentially expressed genes (DEGs) including a subset of known direct transcriptional targets of PRR proteins within core oscillator, including CCA1, LHY, LNKs and RVE8 etc. Intriguingly, PRR proteins can feedback repress BBX28 and BBX29 transcription by associating with their promoters. Together, our findings unmasked an exquisite mechanism in which BBX28 and BBX29 interplay with PRR proteins to fine-tune the circadian pace.
Topics: Arabidopsis; Transcription Factors; Arabidopsis Proteins; Circadian Clocks; Circadian Rhythm; Gene Expression Regulation, Plant
PubMed: 37312621
DOI: 10.1111/pce.14648 -
The Plant Journal : For Cell and... Dec 2023Perennial monocarpic mass flowering represents as a key developmental innovation in flowering time diversity in several biological and economical essential families,...
Perennial monocarpic mass flowering represents as a key developmental innovation in flowering time diversity in several biological and economical essential families, such as the woody bamboos and the shrubby Strobilanthes. However, molecular and genetic mechanisms underlying this important biodiversity remain poorly investigated. Here, we generated a full-length transcriptome resource incorporated into the BlueOmics database (http://blueomics.iflora.cn) for two Strobilanthes species, which feature contrasting flowering time behaviors. Using about 112 and 104 Gb Iso-seq reads together with ~185 and ~75 Gb strand-specific RNA seq data, we annotated 80 971 and 79 985 non-redundant full-length transcripts for the perennial polycarpic Strobilanthes tetrasperma and the perennial monocarpic Strobilanthes biocullata, respectively. In S. tetrasperma, we identified 8794 transcripts showing spatiotemporal expression in nine tissues. In leaves and shoot apical meristems at two developmental stages, 977 and 1121 transcripts were differentially accumulated in S. tetrasperma and S. biocullata, respectively. Interestingly, among the 33 transcription factors showing differential expression in S. tetrasperma but without differential expression in S. biocullata, three were involved potentially in the photoperiod and circadian-clock pathway of flowering time regulation (FAR1 RELATED SEQUENCE 12, FRS12; NUCLEAR FACTOR Y A1, NFYA1; PSEUDO-RESPONSE REGULATOR 5, PRR5), hence provides an important clue in deciphering the flowering diversity mechanisms. Our data serve as a key resource for further dissection of molecular and genetic mechanisms underpinning key biological innovations, here, the perennial monocarpic mass flowering.
Topics: Humans; Transcriptome; Flowers; Gene Expression Profiling; Plant Leaves; RNA-Seq; Gene Expression Regulation, Plant
PubMed: 37665679
DOI: 10.1111/tpj.16452 -
International Journal of Molecular... Nov 2023() play key roles in the circadian rhythms and flowering in plants. Here, we identified the four members of the family in , including , , and , and isolated their...
() play key roles in the circadian rhythms and flowering in plants. Here, we identified the four members of the family in , including , , and , and isolated their retrotransposon-tagged mutants. They were expressed in different organs and were nuclear-localized. The four genes played important roles in normal clock rhythmicity maintenance by negatively regulating the expression of and . Surprisingly, the four functioned redundantly in regulating flowering time under long-day conditions, and the quadruple mutant flowered earlier. Moreover, MtPRR can recruit the MtTPL/MtTPR corepressors and the other MtPRRs to form heterodimers to constitute the core mechanism of the circadian oscillator.
Topics: Circadian Clocks; Medicago truncatula; Arabidopsis; Circadian Rhythm; Photoperiod; Gene Expression Regulation, Plant
PubMed: 38069157
DOI: 10.3390/ijms242316834 -
Physiologia Plantarum 2023Under severe environmental stress conditions, plants inhibit their growth and development and initiate various defense mechanisms to survive. The pseudo-response...
Under severe environmental stress conditions, plants inhibit their growth and development and initiate various defense mechanisms to survive. The pseudo-response regulator (PRRs) genes have been known to be involved in fruit ripening and plant immunity in various plant species, but their role in responses to environmental stresses, especially high salinity and dehydration, remains unclear. Here, we focused on PRRs in tomato plants and identified two PRR2-like genes, SlSRP1 and SlSRP1H, from the leaves of salt-treated tomato plants. After exposure to dehydration and high-salt stresses, expression of SISRP1, but not SlSRP1H, was significantly induced in tomato leaves. Subcellular localization analysis showed that SlSRP1 was predominantly located in the nucleus, while SlSRP1H was equally distributed in the nucleus and cytoplasm. To further investigate the potential role of SlSRP1 in the osmotic stress response, we generated SISRP1-silenced tomato plants. Compared to control plants, SISRP1-silenced tomato plants exhibited enhanced tolerance to high salinity, as evidenced by a high accumulation of proline and reduced chlorosis, ion leakage, and lipid peroxidation. Moreover, SISRP1-silenced tomato plants showed dehydration-tolerant phenotypes with enhanced abscisic acid sensitivity and increased expression of stress-related genes, including SlRD29, SlAREB, and SlDREB2. Overall, our findings suggest that SlSRP1 negatively regulates the osmotic stress response.
Topics: Dehydration; Solanum lycopersicum; Plant Proteins; Sodium Chloride; Abscisic Acid; Stress, Physiological; Plants, Genetically Modified; Gene Expression Regulation, Plant
PubMed: 38148202
DOI: 10.1111/ppl.14082 -
Plant & Cell Physiology Dec 2023Circadian clocks are biological timekeeping systems that coordinate genetic, metabolic and physiological behaviors with the external day-night cycle. The clock in plants...
Circadian clocks are biological timekeeping systems that coordinate genetic, metabolic and physiological behaviors with the external day-night cycle. The clock in plants relies on the transcriptional-translational feedback loops transcription-translation feedback loop (TTFL), consisting of transcription factors including PSUEDO-RESPONSE REGULATOR (PRR) proteins, plant lineage-specific transcriptional repressors. Here, we report that a novel synthetic small-molecule modulator, 5-(3,4-dichlorophenyl)-1-phenyl-1,7-dihydro-4H-pyrazolo[3,4-d] pyrimidine-4,6(5H)-dione (TU-892), affects the PRR7 protein amount. A clock reporter line of Arabidopsis was screened against the 10,000 small molecules in the Maybridge Hitfinder 10K chemical library. This screening identified TU-892 as a period-lengthening molecule. Gene expression analyses showed that TU-892 treatment upregulates CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) mRNA expression. TU-892 treatment reduced the amount of PRR7 protein, a transcriptional repressor of CCA1. Other PRR proteins including TIMING OF CAB EXPRESSION 1 were altered less by TU-892 treatment. TU-892-dependent CCA1 upregulation was attenuated in mutants impaired in PRR7. Collectively, TU-892 is a novel type of clock modulator that reduces the levels of PRR7 protein.
Topics: Arabidopsis Proteins; Circadian Rhythm; Transcription Factors; Arabidopsis; Circadian Clocks; Gene Expression Regulation, Plant
PubMed: 37705303
DOI: 10.1093/pcp/pcad107