Spearsbrennan8864

Breathing is highly sensitive to the PCO2 of arterial blood. Although CO2 is detected via the proxy of pH, CO2 acting directly via Cx26 may also contribute to the regulation of breathing. Here we exploit our knowledge of the structural motif of CO2-binding to Cx26 to devise a dominant negative subunit (Cx26DN) that removes the CO2-sensitivity from endogenously expressed wild type Cx26. Expression of Cx26DN in glial cells of a circumscribed region of the mouse medulla - the caudal parapyramidal area - reduced the adaptive change in tidal volume and minute ventilation by approximately 30% at 6% inspired CO2. As central chemosensors mediate about 70% of the total response to hypercapnia, CO2-sensing via Cx26 in the caudal parapyramidal area contributed about 45% of the centrally-mediated ventilatory response to CO2. Our data unequivocally link the direct sensing of CO2 to the chemosensory control of breathing and demonstrates that CO2-binding to Cx26 is a key transduction step in this fundamental process.Binarization is a critical step in analysis of retinal optical coherence tomography angiography (OCTA) images, but the repeatability of metrics produced from various binarization methods has not been fully assessed. This study set out to examine the repeatability of OCTA quantification metrics produced using different binarization thresholding methods, all of which have been applied in previous studies, across multiple devices and plexuses. Successive 3 × 3 mm foveal OCTA images of 13 healthy eyes were obtained on three different devices. For each image, contrast adjustments, 3 image processing techniques (linear registration, histogram normalization, and contrast-limited adaptive histogram equalization), and 11 binarization thresholding methods were independently applied. Vessel area density (VAD) and vessel length were calculated for retinal vascular images. Choriocapillaris (CC) images were quantified for VAD and flow deficit metrics. Repeatability, measured using the intra-class correlation coefficient, was inconsistent and generally not high (ICC  less then  0.8) across binarization thresholds, devices, and plexuses. In retinal vascular images, local thresholds tended to incorrectly binarize the foveal avascular zone as white (i.e., wrongly indicating flow). No image processing technique analyzed consistently resulted in highly repeatable metrics. Across contrast changes, retinal vascular images showed the lowest repeatability and CC images showed the highest.Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced moentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.Genetic programs operating in a history-dependent fashion are ubiquitous in nature and govern sophisticated processes such as development and differentiation. The ability to systematically and predictably encode such programs would advance the engineering of synthetic organisms and ecosystems with rich signal processing abilities. Here we implement robust, scalable history-dependent programs by distributing the computational labor across a cellular population. Our design is based on standardized recombinase-driven DNA scaffolds expressing different genes according to the order of occurrence of inputs. These multicellular computing systems are highly modular, do not require cell-cell communication channels, and any program can be built by differential composition of strains containing well-characterized logic scaffolds. We developed automated workflows that researchers can use to streamline program design and optimization. We anticipate that the history-dependent programs presented here will support many applications using cellular populations for material engineering, biomanufacturing and healthcare.An amendment to this paper has been published and can be accessed via a link at the top of the paper.The geometry of an inductor made of a long thin wire and having the highest possible Q-factor is found by numerical optimization. As frequency increases, the Q-factor first grows linearly and then according to a square-root law, while the cross-section of the optimal coil evolves from near-circular to sickle-shaped.Black phase CsPbI3 is attractive for optoelectronic devices, while usually it has a high formation energy and requires an annealing temperature of above 300 °C. selleckchem The formation energy can be significantly reduced by adding HI in the precursor. However, the resulting films are not suitable for light-emitting applications due to the high trap densities and low photoluminescence quantum efficiencies, and the low temperature formation mechanism is not well understood yet. Here, we demonstrate a general approach for deposition of γ-CsPbI3 films at 100 °C with high photoluminescence quantum efficiencies by adding organic ammonium cations, and the resulting light-emitting diode exhibits an external quantum efficiency of 10.4% with suppressed efficiency roll-off. We reveal that the low-temperature crystallization process is due to the formation of low-dimensional intermediate states, and followed by interionic exchange. This work provides perspectives to tune phase transition pathway at low temperature for CsPbI3 device applications.