Kochlu4041

Furthermore, siRNA knockdown of p53 in fibroblasts reduced split-dose recovery. In summary, cells defective in p53 are less sensitive to radiotherapy fraction size and lack of split-dose recovery in DNA ligase IV and DNA-PKcs mutant cells suggests the dependence of fraction size sensitivity on intact NHEJ.The study investigated the effect of single and chronic (10 sessions) whole-body cryotherapy (WBC; 3-min, - 110 °C) on amino acid (AA) profile, myostatin, fibroblast growth factor 21 (FGF21), and concentrations of brain-derived neurotrophic factor (BDNF), irisin and adiponectin in relation to glucose homeostasis. Thirty-five, healthy men were randomly split into experimental (young 28 ± 7 years and middle-aged 51 ± 3 years) and control groups. Blood samples were taken before and 1 h after the first and last (10th) WBC session. Baseline myostatin correlated significantly with visceral fat area, glucose, insulin, HOMA-IR and irisin (all p  less then  0.05). The single session of WBC induced temporary changes in AA profile, whereas chronic exposure lowered valine and asparagine concentrations (p  less then  0.01 and p = 0.01, respectively) compared to the baseline. The chronic WBC reduced fasting glucose (p = 0.04), FGF21 (- 35.8%, p = 0.06) and myostatin (-18.2%, p = 0.06). Still, the effects were age-dependent. The decrease of myostatin was more pronounced in middle-aged participants (p  less then  0.01). Concentrations of irisin and adiponectin increased in response to chronic WBC, while BDNF level remained unchanged. By improving the adipo-myokine profile, chronic WBC may reduce effectively the risk of the metabolic syndrome associated with hyperinsulinemia, increased levels of valine and asparagine, and muscle atrophy.Programmed cell death (PCD) is one of the most intensively researched fields in modern mammalian biology with roles in cancer, aging, diabetes and numerous neurodegenerative diseases. It is becoming increasingly clear that PCD also plays significant roles in plant defence and responses to the environment. Given their unique ability to tolerate desiccation (cells remain viable even after they've lost 95% of their water), resurrection plants make ideal models to study the regulation of plant PCD pathways. PF-07081532 Previously, we showed that the Australian resurrection plant, Tripogon loliiformis, suppresses plant PCD, via trehalose-mediated activation of autophagy pathways, during drying. In the present study, we created a full-length T. loliiformis cDNA library, performed a large-scale Agrobacterium screen for improved salinity tolerance and identified Stachyose synthase (TlStach) as a potential candidate for improving stress tolerance. Tripogon loliiformis shoots accumulate stachyose synthase transcripts and stachyose during drying. Attempts to generate transgenic plants expressing TlStach failed and were consistent with previous reports in mammals that demonstrated stachyose-mediated induction of apoptosis. Using a combination of transcriptomics, metabolomics and cell death assays (TUNNEL and DNA laddering), we investigated whether stachyose induces apoptotic-like cell death in T. loliiformis. We show that stachyose triggers the formation of the hallmarks of plant apoptotic-like cell death in the desiccation sensitive Nicotiana benthamiana but not the resilient T. loliiformis. These findings suggest that T. loliiformis suppresses stachyose-mediated apoptotic-like cell death and provides insights on the role of sugar metabolism and plant PCD pathways. A better understanding of how resilient plants regulate sugar metabolism and PCD pathways may facilitate future targeting of plant metabolic pathways for increased stress tolerance.Parabiosis experiments suggest that molecular factors related to rejuvenation and aging circulate in the blood. Here, we show that miR-199-3p, which circulates in the blood as a cell-free miRNA, is significantly decreased in the blood of aged mice compared to young mice; and miR-199-3p has the ability to enhance myogenic differentiation and muscle regeneration. Administration of miR-199 mimics, which supply miR-199-3p, to aged mice resulted in muscle fiber hypertrophy and delayed loss of muscle strength. Systemic administration of miR-199 mimics to mdx mice, a well-known animal model of Duchenne muscular dystrophy (DMD), markedly improved the muscle strength of mice. Taken together, cell-free miR-199-3p in the blood may have an anti-aging effect such as a hypertrophic effect in aged muscle fibers and could have potential as a novel RNA therapeutic for DMD as well as age-related diseases. The findings provide us with new insights into blood-circulating miRNAs as age-related molecules.Disc coal samples with different water content were tested using the split Hopkinson press bar test system. Their dynamic tensile failure process was monitored via an ultra-high-speed digital image correlation system. The deformation trend and failure characteristics as a function of the water content were analyzed, and the water content effect on dynamic mechanical properties was investigated. The results demonstrated that the dynamic stress-strain curve of the coal samples consisted of four stages. As the water content increased, the coal sample brittleness degraded, while its ductility was enhanced. Quadratic polynomial functions can describe dynamic peak stress, peak strain, and loading pressure. Under different loading pressures, the dynamic peak stress exhibited a concave bending trend as the water content increased. The coal sample's dynamic tensile strength had a strong rate correlation, and the saturated coal sample exhibited the highest rate correlation. Under high-rate loading, the inertia effect and the Stefan effect of water in coal samples hinder the initiation and propagation of coal sample cracks, improving the coal sample's strength. The research results provide a basic theoretical basis for the prevention and control of rock burst in coal mines.In this work, a mid-wavelength infrared separate absorption and multiplication avalanche photodiode (SAM-APD) with 100% cut-off wavelength of ~ 5.0 µm at 200 K grown by molecular beam epitaxy was demonstrated. The InAsSb-based SAM-APD device was designed to have electron dominated avalanche mechanism via the band structure engineered multi-quantum well structure based on AlAsSb/GaSb H-structure superlattice and InAsSb material in the multiplication region. The device exhibits a maximum multiplication gain of 29 at 200 K under -14.7 bias voltage. The maximum multiplication gain value for the MWIR SAM-APD increases from 29 at 200 K to 121 at 150 K. The electron and hole impact ionization coefficients were derived and the large difference between their value was observed. The carrier ionization ratio for the MWIR SAM-APD device was calculated to be ~ 0.097 at 200 K.