O-HO PET/CT is safe and effective for the early detection and quantitative analysis of subclinical post-RT changes in heart perfusion in breast cancer patients. The LV segments supplied by the LAD are the main site of MBF changes. A minimum radiation dose deposited in the LAD may be a predictor of radiation-induced heart toxicity. Advances in knowledge: This is the first time that O-HO PET/CT has been used to assess MBF after RT and the first granular description of the distribution of blood flow changes after breast cancer RT.
Gene regulation ensures that the appropriate genes are expressed at the proper times. Nuclear retention of incompletely spliced or mature mRNAs emerges as a novel, previously underappreciated layer of post-transcriptional gene regulation. Studies on this phenomenon indicated that it exerted significant impact on the regulation of gene expression by regulating export and translation delay, which allows synthesis of specific proteins in response to a stimulus, e.g. under stress conditions or at strictly controlled time points, e.g. during cell differentiation or development. Here, we found that transcription in microsporocytes, during prophase of the first meiotic division, occurs in pulsatile manner. After each pulse, the transcriptional activity is silenced, but the transcripts synthesized at this time are not exported immediately to the cytoplasm, but are retained in the nucleoplasm and Cajal bodies (CBs). In contrast to nucleoplasm, mature transcripts were not found in CBs. Only non-fully-spliced transcripts with retained introns were stored in the CBs. Retained introns are spliced at precisely defined times, and fully mature mRNAs are released into the cytoplasm, where the proteins are produced. These proteins are necessary for further cell development during meiotic prophase. Our findings provide new insight into the regulatory mechanisms of gene expression based on mRNA retention in the nucleus during the development of generative cells in plants. Similar processes were observed during spermatogenesis in animals. This indicates the existence of an evolutionarily conserved mechanism of gene expression regulation during generative cells development in Eukaryota.
Gene regulation ensures that the appropriate genes are expressed at the proper time. Nuclear retention of incompletely spliced or mature mRNAs is emerging as a novel, previously underappreciated layer of post-transcriptional regulation. Studies on this phenomenon indicated that it exerts a significant influence on the regulation of gene expression by regulating export and translation delay, which allows the synthesis of specific proteins in response to a stimulus or at strictly controlled time points, e.g. during cell differentiation or development. Here, we show that transcription in microsporocytes of European larch (Larix decidua) occurs in a pulsatile manner during prophase of the first meiotic division. Transcriptional activity was then silenced after each pulse. However, the transcripts synthesized were not exported immediately to the cytoplasm but were retained in the nucleoplasm and Cajal bodies (CBs). In contrast to the nucleoplasm, we did not detect mature transcripts in CBs, which only stored non-fully-spliced transcripts with retained introns. Notably, the retained introns were spliced at precisely defined times, and fully mature mRNAs were released into the cytoplasm for translation. As similar processes have been observed during spermatogenesis in animals, our results illustrate an evolutionarily conserved mechanism of gene expression regulation during generative cells development in Eukaryota.
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Background: Relatives of critically ill patients who either die or survive the intensive care unit (ICU) may develop substantial mental health problems that are collectively defined as Post-Intensive Care Syndrome in Family (PICS-F). It is important to document in a systematic manner all of the possible risk factors associated with the development of the latter.Methods: By using a systematized search strategy we included studies that focused on PICS-F in relatives of adult ICU patients and reported the risk factors associated with its development. The search was conducted within PubMed, Embase, SCOPUS, clinicaltrials.gov and Cochrane Library on the 2nd of May, 2021. PRISMA guidelines were implemented for appropriate reporting. Results: We included 52 papers covering 8293 relatives. The prevalence of PICS-F varied between 2.5-69%. We identified over 70 different risk factors of PICS-F, among which we distinguished patient-related (n=28), relative-related (n=33) and medical staff-related (n=9) risk factors. Among 17 studies with the highest quality we identified the 7 following factors associated with the development of PICS-F: younger age of a patient, death of a patient, depression in relatives during the ICU stay, history of mental disorders in relatives, being a spouse and low satisfaction with communication & care in the ICU.Conclusions: PICS-F is a highly prevalent phenomenon that may be exacerbated by a number of risk factors. Special attention should be paid to proper identification of susceptible relatives in order to prevent PICS.
Recent studies show a crucial role of post-transcriptional processes in the regulation of gene expression. Our research has shown that mRNA retention in the nucleus plays a significant role in such regulation. We studied larch microsporocytes during meiotic prophase, characterized by pulsatile transcriptional activity. After each pulse, the transcriptional activity is silenced, but the transcripts synthesized at this time are not exported immediately to the cytoplasm but are retained in the cell nucleus and especially in Cajal bodies, where non-fully-spliced transcripts with retained introns are accumulated. Analysis of the transcriptome of these cells and detailed analysis of the nuclear retention and transport dynamics of several mRNAs revealed two main patterns of nuclear accumulation and transport. The majority of studied transcripts followed the first one, consisting of a more extended retention period and slow release to the cytoplasm. We have shown this in detail for the pre-mRNA and mRNA encoding RNA pol II subunit 10. In this pre-mRNA, a second (retained) intron is posttranscriptionally spliced at a precisely defined time. Fully mature mRNA is then released into the cytoplasm, where the RNA pol II complexes are produced. These proteins are necessary for transcription in the next pulse to occur.mRNAs encoding translation factors and SERRATE followed the second pattern, in which the retention period was shorter and transcripts were rapidly transferred to the cytoplasm. The presence of such a mechanism in various cell types from a diverse range of organisms suggests that it is an evolutionarily conserved mechanism of gene regulation.
Background Urinary tract infections (UTI) represent one of the most common contagious diseases in humans. Uropathogenic Escherichia coli (UPEC) strains are recognized as the most frequent causative agent, and these express a range of virulence factors including the adhesins. Immune response to UPEC under immunosuppression has not been fully understood yet. Interleukin 1β (IL1β), 6 (IL6) and 17 (IL17) represent clinically relevant markers of inflammation. Aim The study aimed to investigate the interplay between UPEC genotype and hosts’ immune status in shaping local inflammatory response in the course of an UTI episode. The respective numbers of: 18 kidney recipients with UPEC UTI, 28 immunocompetent hosts with UPEC UTI and 29 healthy controls were involved. Urine IL1β, IL6, and IL17/creatinine ratios in relation to fimH, csgA, papC, tosA, and flu genes presence in UPEC isolated from the urine samples were analyzed. Apart from traditional statistics, also machine learning algorithms were applied. Results The urine levels of IL1β and IL 6 were similar in kidney recipients and the immunocompetent hosts. IL1β levels were higher in both kidney recipients and immunocompetent hosts than in controls, while IL6 levels were higher only in immunocompetent hosts than in controls. In the machine learning classification model, high urine IL17 levels were significantly more prevalent in controls, while low IL17 levels in urines infected with Ag43-positive UPEC strains, regardless of the host’s immune status. In the traditional statistical analysis, IL17 levels appeared significantly higher in urine samples from kidney recipients infected with Ag43–negative UPEC strains. Conclusions In the UTI- affected patients, the combination of the immune status of an individual and Ag43 status of the UPEC strain determined urine IL17 level in the analyzed group. However, IL17 levels above median were overall more prevalent in controls.
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