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Immunoglobulin class switch recombination (CSR) occurs in activated B cells with increased mitochondrial mass and membrane potential. Transcription factor Yin Yang 1 (YY1) is critical for CSR and for formation of the DNA loops involved in this process. We therefore sought to determine if YY1 knockout impacts mitochondrial gene expression and mitochondrial function in murine splenic B cells, providing a potential mechanism for regulating CSR. Selleckchem GDC-6036 We identified numerous genes in splenic B cells differentially regulated when cells are induced to undergo CSR. YY1 conditional knockout caused differential expression of 1129 genes, with 59 being mitochondrial-related genes. ChIP-seq analyses showed YY1 was directly bound to nearly half of these mitochondrial-related genes. Surprisingly, at the time when YY1 knockout dramatically reduces DNA loop formation and CSR, mitochondrial mass and membrane potential were not significantly impacted, nor was there a significant change in mitochondrial oxygen consumption, extracellular acidification rate, or mitochondrial complex I or IV activities. Our results indicate that YY1 regulates numerous mitochondrial-related genes in splenic B cells, but this does not account for the impact of YY1 on CSR or long-distance DNA loop formation. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.AIM The clinical features and implications of dizziness in patients with Parkinson's disease (PD) remain little known. This study aimed to investigate the clinical characteristics of dizziness, and the association of dizziness with motor and non-motor symptoms in early stages of PD. METHODS Demographics and clinical characteristics of patients with early PD (disease duration ≤5 years) were retrospectively assessed. The characteristics of dizziness were surveyed in each parkinsonian patient according to existence, frequency, duration and nature. Not only motor symptoms, but also non-motor scales for global cognition, anxiety, depression and fatigue were evaluated to identify risk factors of dizziness. RESULTS Of a total of 80 patients with early PD, 37 (46.3%) had dizziness. The characteristics of dizziness included short duration (seconds to minutes) and frequent occurrence (several times in a day or a week). The most common type of dizziness was orthostatic (40.5%), followed by non-specific and disequilibrium type. Among many scales for motor and non-motor symptoms, dizzy patients with early PD showed lower scores of Montreal Cognitive representing global cognition than non-dizzy people. A lower Montreal Cognitive Assessment score was the only factor significantly related to dizziness in patients with early PD. CONCLUSIONS We found that dizziness frequently occurs in early parkinsonian patients. It is highly linked to low Montreal Cognitive Assessment scores in patients with early PD, inferring that dizziness might be a potential non-motor symptom associated with cognitive decline in PD. Geriatr Gerontol Int 2020; •• ••-••. © 2020 Japan Geriatrics Society.BACKGROUND Numerous abnormally expressed miRs have been reported involved in oxaliplatin (L-OHP) resistance of colorectal cancer (CRC). The present study aimed to investigate whether miR-200b-3p could regulate L-OHP resistance via targeting TUBB3 in CRC cells. METHODS L-OHP resistant HT29 and HCT116 cells were exposed to escalating concentrations of L-OHP up to 30 μm. The effect of miR-200b-3p on L-OHP resistant CRC cells was then evaluated using the cell counting kit-8 (CCK-8) assay. CRC cell apoptosis was detected using Annexin V-FITC/PI double staining. Bioinformatics algorithms and luciferase reporter assays were also performed to investigate whether TUBB3 was a direct target of miR-200b-3p. RESULTS miR-200b-3p declined in L-OHP resistant CRC tissues and cell lines, and the overexpression of miR-200b-3p elevated the L-OHP sensitivity in L-OHP resistant HT29 and HCT116 cells. In addition, we determined the potential mechanisms underlying miR-200b-3p-mediated reversal of L-OHP resistance by mediating its downstream target TUBB3, and the overexpression of miR-200b-3p could induce migration and growth inhibition and apoptosis in L-OHP resistant HT29 and HCT116 cells by silencing βIII-tubulin protein expression. However, the overexpression of TUBB3 reversed miR-200b-3p mimic-induced migration, as well as growth inhibition and apoptosis, in L-OHP resistant CRC cells. CONCLUSIONS miR-200b-3p improved L-OHP resistance and induced growth inhibition and cell apoptosis in L-OHP resistant CRC cells, and the underlying mechanism was mediated, at least partially, through the suppression of βIII-tubulin protein expression. © 2020 John Wiley & Sons, Ltd.The use of a fluorescent dye to visualize cellular material on surfaces offers a targeted sampling approach for locating touch DNA on casework items. However, the current application of such dye is not feasible for examination of relatively large items. As a result, development of an efficient dye application system is required to translate this approach into practice. Here, the spray pattern (area covered, intensity, and evenness) of 15 different commercial spray devices was examined visually using food coloring. From this, five devices were selected to apply Diamond Nucleic Acid Dye (DD) to three substrates (glass slide, plastic sheet, and brown packing tape) seeded with saliva and touch DNA. The cellular material was visualized using the Dino-lite Microscope and Polilight. The inhibitory effects of DD afforded by each spray device were examined using Identifiler Plus® DNA profiling kit and a DNA input of 800 pg. The two most promising devices were further tested on a range of mock casework items seeded with touch DNA. The results presented demonstrate the feasibility of a spray system to apply DD to large surfaces and subsequently detect cellular material at both micro and macroscale. Specifically, the data suggest that a pressurized continuous-spray system is favorable and that droplet size influences the intensity of fluorescence and surface coverage. Furthermore, this study indicates that full STR profiles can be obtained following spraying with DD solution, even with excessive application, which is essential for the widespread use of these devices in casework. © 2020 American Academy of Forensic Sciences.
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