Notes

CE: Autism Array Disorder: The Nurse's Role.
Our results identify UFMylation as a crucial post-translational modification for maintenance of p53 stability and tumour-suppressive function, and point to UFMylation as a promising therapeutic target in cancer.Cancer represents an evolutionary process through which growing malignant populations genetically diversify, leading to tumour progression, relapse and resistance to therapy. In addition to genetic diversity, the cell-to-cell variation that fuels evolutionary selection also manifests in cellular states, epigenetic profiles, spatial distributions and interactions with the microenvironment. Therefore, the study of cancer requires the integration of multiple heritable dimensions at the resolution of the single cell - the atomic unit of somatic evolution. In this Review, we discuss emerging analytic and experimental technologies for single-cell multi-omics that enable the capture and integration of multiple data modalities to inform the study of cancer evolution. These data show that cancer results from a complex interplay between genetic and non-genetic determinants of somatic evolution.Adeno-associated viral vectors (AAV) are unique in their ability to transduce a variety of both dividing and nondividing cells, with significantly lower risk of random genomic integration and with no known pathogenicity in humans, but their role in ex vivo regional gene therapy for bone repair has not been definitively established. The goal of this study was to test the ability of AAV vectors carrying the cDNA for BMP-2 to transduce human mesenchymal stem cells (MSCs), produce BMP-2, and induce osteogenesis in vitro as compared with lentiviral gene therapy with a two-step transcriptional amplification system lentiviral vector (LV-TSTA). To this end, we created two AAV vectors (serotypes 2 and 6) expressing the target transgene; eGFP or BMP-2. Transduction of human MSCs isolated from bone marrow (BMSCs) or adipose tissue (ASCs) with AAV2-eGFP and AAV6-eGFP led to low transduction efficiency (BMSCs 3.57% and 8.82%, respectively, ASCs 6.17 and 20.2%, respectively) and mean fluorescence intensity as seen with FAC applications.During the last 20 years, the role of musicians' body movements has emerged as a central question in instrument practice Why do musicians make so many postural movements, for instance, with their torsos and heads, while playing musical instruments? The musical significance of such ancillary gestures is still an enigma and therefore remains a major pedagogical challenge, since one does not know if these movements should be considered essential embodied skills that improve musical expressivity. Although previous studies established clear connections between musicians' body movements and musical structures (particularly for clarinet, piano or violin performances), no evidence of direct relationships between body movements and the quality of the produced timbre has ever been found. In this study, focusing on the area of bowed-string instruments, we address the problem by showing that cellists use a set of primary postural directions to develop fluid kinematic bow features (velocity, acceleration) that prevent the production of poor quality (i.e., harsh, shrill, whistling) sounds. By comparing the body-related angles between normal and posturally constrained playing situations, our results reveal that the chest rotation and vertical inclination made by cellists act as coordinative support for the kinematics of the bowing gesture. These findings support the experimental works of Alexander, especially those that showed the role of head movements with respect to the upper torso (the so-called primary control) in ensuring the smooth transmission of fine motor control in musicians all the way to the produced sound. More generally, our research highlights the importance of focusing on this fundamental postural sense to improve the quality of human activities across different domains (music, dance, sports, rehabilitation, working positions, etc.).Evaluating the performance of photoplethysmogram (PPG) event detection algorithms requires a large number of PPG signals with different noise levels and sampling frequencies. As publicly available PPG databases provide few options, artificially constructed PPG signals can also be used to facilitate this evaluation. Here, we propose a dynamic model to synthesize PPG over specified time durations and sampling frequencies. In this model, a single pulse was simulated by two Gaussian functions. Additionally, the beat-to-beat intervals were simulated using a normal distribution with a specific mean value and a specific standard deviation value. To add periodicity and to generate a complete signal, the circular motion principle was used. We synthesized three classes of pulses by emulating three different templates excellent (systolic and diastolic waves are salient), acceptable (systolic and diastolic waves are not salient), and unfit (systolic and diastolic waves are noisy). The optimized model fitting of the Gaussian functions to the templates yielded 0.99, 0.98, and 0.85 correlations between the template and synthetic pulses for the excellent, acceptable, and unfit classes, respectively, with mean square errors of 0.001, 0.003, and 0.017, respectively. By comparing the heart rate variability of real PPG and randomly synthesized PPG for 5 min in 116 records from the MIMIC III database, strong correlations were found in SDNN, RMSSD, LF, HF, SD1, and SD2 (0.99, 0.89, 0.84, 0.89, 0.90 and 0.95, respectively).Micro-CT scan images enhanced by iodine staining provide high-resolution visualisation of soft tissues in laboratory mice. We have compared Micro-CT scan-derived left ventricular (LV) mass with dissection and weighing. Ex-vivo micro-CT scan images of the mouse hearts were obtained following staining by iodine. The LV was segmented and its volume was assessed using a semi-automated method by Drishti software. The left ventricle was then dissected in the laboratory and its actual weight was measured and compared against the estimated results. LV mass was calculated multiplying its estimated volume and myocardial specific gravity. Thirty-five iodine-stained post-natal mouse hearts were studied. Mice were of either sex and 68 to 352 days old (median age 202 days with interquartile range 103 to 245 days) at the time of sacrifice. Samples were from 20 genetically diverse strains. Median mouse body weight was 29 g with interquartile range 24 to 34 g. Left Ventricular weights ranged from 40.0 to 116.7 mg. The segmented LV mass estimated from micro-CT scan and directly measured dissected LV mass were strongly correlated (R2 = 0. 97). Segmented LV mass derived from Micro-CT images was very similar to the physically dissected LV mass (mean difference = 0.09 mg; 95% confidence interval - 3.29 mg to 3.1 mg). Micro-CT scanning provides a non-destructive, efficient and accurate visualisation tool for anatomical analysis of animal heart models of human cardiovascular conditions. Iodine-stained soft tissue imaging empowers researchers to perform qualitative and quantitative assessment of the cardiac structures with preservation of the samples for future histological analysis.The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The virus has rapidly spread in humans, causing the ongoing Coronavirus pandemic. Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises the Spike glycoprotein on the envelope to recognise and bind the human receptor ACE2. This event initiates the fusion of viral and host cell membranes and then the viral entry into the host cell. Despite several ongoing clinical studies, there are currently no approved vaccines or drugs that specifically target SARS-CoV-2. Until an effective vaccine is available, repurposing FDA approved drugs could significantly shorten the time and reduce the cost compared to de novo drug discovery. In this study we attempted to overcome the limitation of in silico virtual screening by applying a robust in silico drug repurposing strategy. We combined and integrated docking simulations, with molecular dynamics (MD), Supervised MD (SuMD) and Steered MD (SMD) simulations to identify a Spike protein - ACE2 interaction inhibitor. Our data showed that Simeprevir and Lumacaftor bind the receptor-binding domain of the Spike protein with high affinity and prevent ACE2 interaction.China is a major coal-producing country that consumes large amounts of coal every year. Due to the existence of many small coal kilns using backward mining methods, numerous worked-out areas have been formed. The coal mines were abandoned with no mitigation, so air penetrates into the roadways and contacts the coal seams; as a result, the residual coal seams spontaneously ignite to form coal fires. These coal fires have burned millions of tons of valuable coal resources and caused serious environmental problems. To implement fire suppression more effectively, coal fire detection is a key technology. In this paper, thermal infrared remote sensing from unmanned aerial vehicle combined with a surface survey is used to identify the range of coal fires in the Huojitu coal mine in Shenmu city. The scopes and locations of the fire zones are preliminarily delineated, which provides an accurate basis for the development of fire suppression projects.Dissimilatory sulfate reduction (DSR)-an important reaction in the biogeochemical sulfur cycle-has been dated to the Palaeoarchaean using geological evidence, but its evolutionary history is poorly understood. Several lineages of bacteria carry out DSR, but in archaea only Archaeoglobus, which acquired DSR genes from bacteria, has been proven to catalyse this reaction. We investigated substantial rates of sulfate reduction in acidic hyperthermal terrestrial springs of the Kamchatka Peninsula and attributed DSR in this environment to Crenarchaeota in the Vulcanisaeta genus. Community profiling, coupled with radioisotope and growth experiments and proteomics, confirmed DSR by 'Candidatus Vulcanisaeta moutnovskia', which has all of the required genes. Other cultivated Thermoproteaceae were briefly reported to use sulfate for respiration but we were unable to detect DSR in these isolates. Phylogenetic studies suggest that DSR is rare in archaea and that it originated in Vulcanisaeta, independent of Archaeoglobus, by separate acquisition of qmoABC genes phylogenetically related to bacterial hdrA genes.Bacteria respond to changes in their environment with specific transcriptional programmes, but even within genetically identical populations these programmes are not homogenously expressed1. Such transcriptional heterogeneity between individual bacteria allows genetically clonal communities to develop a complex array of phenotypes1, examples of which include persisters that resist antibiotic treatment and metabolically specialized cells that emerge under nutrient-limiting conditions2. Fluorescent reporter constructs have played a pivotal role in deciphering heterogeneous gene expression within bacterial populations3 but have been limited to recording the activity of single genes in a few genetically tractable model species, whereas the vast majority of bacteria remain difficult to engineer and/or even to cultivate. Single-cell transcriptomics is revolutionizing the analysis of phenotypic cell-to-cell variation in eukaryotes, but technical hurdles have prevented its robust application to prokaryotes. Here, using an improved poly(A)-independent single-cell RNA-sequencing protocol, we report the faithful capture of growth-dependent gene expression patterns in individual Salmonella and Pseudomonas bacteria across all RNA classes and genomic regions.
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