Telomeres are long DNA repeats and a protein complex at chromosome ends that are essential for genome integrity. Telomeres are very short in patients with dyskeratosis congenita due to germline ...mutations in telomere biology genes. We compared telomere length in patients with Fanconi anemia, Diamond-Blackfan anemia and Shwachman-Diamond syndrome with telomere length in dyskeratosis congenita. Telomere length was measured in six leukocyte subsets by automated multicolor flow fluorescence in situ hybridization, and age-adjusted using Z-scores (-2.326 = 1(st) percentile) were created. We examined individual data, and used canonical variate analysis for group comparisons and outlier detection. Most dyskeratosis congenita telomere lengths were below the 1(st) percentile, while only 2 Fanconi anemia and one each Diamond-Blackfan anemia and Shwachman-Diamond syndrome were that low. However, Fanconi anemia, Diamond-Blackfan anemia and Shwachman-Diamond syndrome clustered in the bottom half of the normal range. Canonical variate analysis separated dyskeratosis congenita widely from the other three syndromes by the first canonical variable (89.7% of the variance); the second variable (10.0%) separated Diamond-Blackfan anemia, Shwachman-Diamond syndrome, and Fanconi anemia from each other. Overall, unlike in dyskeratosis congenita, telomere lengths in patients with non-dyskeratosis congenita inherited bone marrow failure syndromes were usually in the normal range, albeit shorter than in unaffected individuals. Clinicaltrials.gov identifier: 00027274.
Epigenetic dysregulation has emerged as a major contributor to tumorigenesis. Histone methylation is a well-established mechanism of epigenetic regulation that is dynamically modulated by histone ...methyltransferases and demethylases. The pathogenic role of histone methylation modifiers in non-small cell lung cancer (NSCLC), which is the leading cause of cancer deaths worldwide, remains largely unknown. Here, we found that the histone H3 lysine 36 (H3K36) demethylase KDM2A (also called FBXL11 and JHDM1A) is frequently overexpressed in NSCLC tumors and cell lines. KDM2A and its catalytic activity were required for in vitro proliferation and invasion of KDM2A-overexpressing NSCLC cells. KDM2A overexpression in NSCLC cells with low KDM2A levels increased cell proliferation and invasiveness. KDM2A knockdown abrogated tumor growth and invasive abilities of NSCLC cells in mouse xenograft models. We identified dual-specificity phosphatase 3 (DUSP3) as a key KDM2A target gene and found that DUSP3 dephosphorylates ERK1/2 in NSCLC cells. KDM2A activated ERK1/2 through epigenetic repression of DUSP3 expression via demethylation of dimethylated H3K36 at the DUSP3 locus. High KDM2A levels correlated with poor prognosis in NSCLC patients. These findings uncover an unexpected role for a histone methylation modifier in activating ERK1/2 in lung tumorigenesis and metastasis, suggesting that KDM2A may be a promising therapeutic target in NSCLC.
Abstract Nanotechnology has enabled the engineering of nanostructured materials to meet current challenges in bone replacement therapies. Biocomposite nanofibrous scaffolds of poly( l -lactic acid)- ...co -poly( ε -caprolactone), gelatin and hydroxyapatite (HA) were fabricated by combining the electrospinning and electrospraying techniques in order to create a better osteophilic environment for the growth and mineralization of osteoblasts. Electrospraying of HA nanoparticles on electrospun nanofibers helped to attain rough surface morphology ideal for cell attachment and proliferation and also achieve improved mechanical properties than HA blended nanofibers. Nanofibrous scaffolds showed high pore size and porosity up to 90% with fiber diameter in the range of 200–700 nm. Nanofibrous scaffolds were characterized for their functional groups and chemical structure by FTIR and XRD analysis. Studies on cell–scaffold interaction were carried out by culturing human fetal osteoblast cells (hFOB) on both HA blended and sprayed PLACL/Gel scaffolds and assessing their growth, proliferation, mineralization and enzyme activity. The results of MTS, ALP, SEM and ARS studies confirmed, not only did HA sprayed biocomposite scaffolds showed better cell proliferation but also enhanced mineralization and alkaline phosphatase activity (ALP) proving that electrospraying in combination with electrospinning produced superior and more suitable biocomposite nanofibrous scaffolds for bone tissue regeneration.
•Low pH is a major factor that restricts growth and stability of probiotic bacteria.•Molecular oxygen is detrimental to growth and survival of probiotics especially during storage period.•The process ...of microencapsulation has been used for improving the viability of probiotics in fermented food products.•Antioxidant compounds could be used to limit negative effects of oxygen exposure on probiotic bacteria.•Mild heat treatment before spray drying may enhance cell survival during storage.
Probiotic foods are reported to provide several health benefits, as they help in maintaining a good balance and composition of intestinal flora, and increase the resistance against invasion of pathogens. The demand of probiotic functional foods is growing rapidly due to increased awareness of consumers about the impact of food on health. Development of foods with adequate doses of probiotics at the time of consumption is a challenge, because several factors during processing and storage affect the viability of probiotic organisms. The presence of probiotics in food products may also adversely affect their quality and sensory properties. Several attempts have been made during the last few decades to improve the viability of probiotics in different food products during their production until the time of consumption. Major emphasis has been given to protect the microorganisms with the help of encapsulation technique, by addition of different protectants, and by alteration of processing and storage conditions. This contribution provides an overview of probiotic foods, factors responsible for survival of probiotics, and advance technologies used to stabilize their viability during processing and storage.
Microwave-vacuum dehydration characteristics of button mushroom (
Agaricus bisporus) were evaluated in a commercially available microwave oven (0–600
W) modified to a drying system by incorporating a ...vacuum chamber in the cavity. The effect of drying parameters, namely microwave power, system pressure and product thickness on the drying kinetics and rehydration characteristics were investigated. The drying system was operated in the microwave power range of 115–285
W, pressure range of 6.5–23.5
kPa having mushroom slices of 6–14
mm thickness. Convective air drying at different air temperatures (50, 60 and 70
°C) was performed to compare the drying rate and rehydration properties of microwave-vacuum drying with conventional method. Microwave-vacuum drying resulted in 70–90% decrease in the drying time and the dried products had better rehydration characteristics as compared to convective air drying. The rate constants of the exponential and Page’s model for thin layer drying were established by regression analysis of the experimental data which were found to be affected mainly by the microwave power level followed by sample thickness while system pressure had a little effect on the drying rate. Rehydration ratio was significantly affected by the system pressure. Empirical models are also developed for estimating the drying rate constant and rehydration ratio as a function of the microwave-vacuum drying process parameters.
Steroidal glycoalkaloids (SGAs) such as α-solanine found in solanaceous food plants— as, for example, potato— are antinutritional factors for humans. Comparative coexpression analysis between tomato ...and potato coupled with chemical profiling revealed an array of 10 genes that partake in SGA biosynthesis. We discovered that six of them exist as a cluster on chromosome 7, whereas an additional two are adjacent in a duplicated genomic region on chromosome 12. Following systematic functional analysis, we suggest a revised SGA biosynthetic pathway starting from cholesterol up to the tetrasaccharide moiety linked to the tomato SGA aglycone. Silencing GLYCOALKALOID METABOLISM 4 prevented accumulation of SGAs in potato tubers and tomato fruit. This may provide a means for removal of unsafe, antinutritional substances present in these widely used food crops.
ABSTRACT
A new upper limit on the 21 cm signal power spectrum at a redshift of z ≈ 9.1 is presented, based on 141 h of data obtained with the Low-Frequency Array (LOFAR). The analysis includes ...significant improvements in spectrally smooth gain-calibration, Gaussian Process Regression (GPR) foreground mitigation and optimally weighted power spectrum inference. Previously seen ‘excess power’ due to spectral structure in the gain solutions has markedly reduced but some excess power still remains with a spectral correlation distinct from thermal noise. This excess has a spectral coherence scale of 0.25–0.45 MHz and is partially correlated between nights, especially in the foreground wedge region. The correlation is stronger between nights covering similar local sidereal times. A best 2-σ upper limit of $\Delta ^2_{21} \lt (73)^2\, \mathrm{mK^2}$ at $k = 0.075\, \mathrm{h\, cMpc^{-1}}$ is found, an improvement by a factor ≈8 in power compared to the previously reported upper limit. The remaining excess power could be due to residual foreground emission from sources or diffuse emission far away from the phase centre, polarization leakage, chromatic calibration errors, ionosphere, or low-level radiofrequency interference. We discuss future improvements to the signal processing chain that can further reduce or even eliminate these causes of excess power.
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