Beachcurrie7964

Here we report the development and testing of a novel self-limiting gene drive system, Killer-Rescue (K-R), in Drosophila melanogaster. This system is composed of an autoregulated Gal4 Killer (K) and a Gal4-activated Gal80 Rescue (R). Overexpression of Gal4 is lethal, but in the presence of R activation of Gal80 leads to much lower levels of Gal4 and rescue of lethality. We demonstrate that with a single 2 1 engineered to wild-type release, K drives R through the population and after nine generations, more than 98% of the population carry R and less than 2% of the population are wild-type flies. We discuss how this simple K-R gene drive system may be readily adapted for population replacement in a human health pest, Aedes aegypti, or for population suppression in an agricultural pest, Drosophila suzukii.The novel coronavirus disease 2019 (COVID-19) has grown to be a global public-health emergency since patients were first detected in Wuhan, China, in December 2019. As of April 9, 2020, the novel coronavirus (named as SARS-CoV-2 by the International Committee on Taxonomy of Viruses on February 11) has infected 83,251 and 1,484,811 patients in China and the world, respectively. However, we have neither confirmed effective antiviral medications nor vaccines available to deal with this emergency. read more In this commentary, we offer an alternative promising therapy for COVID-19, that is, mesenchymal stem cell transplantation.Recently, cation exchange chromatography (CEX) using aqueous volatile buffers was directly coupled with mass spectrometry (MS) and applied for intact analysis of therapeutic proteins and antibodies. In our study, chemical modifications responsible for charge variants were identified by CEX-UV-MS for a monoclonal antibody (mAb), a bispecific antibody, and an Fc-fusion protein. We also report post-CEX column addition of organic solvent and acid followed by mixing at elevated temperatures, which unfolded proteins, increased ion intensity (sensitivity) and facilitated top-down analysis. mAb stressed by hydrogen peroxide oxidation was used as a model system, which produced additional CEX peaks. The on-line CEX-UV-MS top-down analysis produced gas-phase fragments containing one or two methionine residues. Oxidation of some methionine residues contributed to earlier (acidic), some to later (basic) eluting peaks, while oxidation of other residues did not change CEX elution. The abundance of the oxidized and non-oxidized fragment ions also allowed estimation of the oxidation percentage of different methionine residues in stressed mAb. CEX-UV-MS measurement revealed a new intact antibody proteoform at 5% that eluted as a basic peak and included paired modifications high-mannose glycosylation and remaining C-terminal lysine residue (M5/M5 + K). This finding was confirmed by peptide mapping and on-column disulfide reduction coupled with reversed-phase liquid chromatography - top-down MS analysis of the collected basic peak. Overall, our results demonstrate the utility of the on-line method in providing site-specific structural information of charge modifications without fraction collection and laborious peptide mapping.The worldwide incidence of traumatic brain injury (TBI) is approximately 0.5% per year and the frequency is significantly higher among military personnel and athletes. Repetitive TBIs are associated with military and athletic activities and typically involve more severe consequences. The majority of TBIs are mild however these still can result in long term cognitive deficits and there is currently no effective treatment. tert-butylhydroquinone (tBHQ) and pioglitazone can activate the Nrf2 and PPAR- transcription factors, respectively, and each has been shown to be neuroprotective in various model systems. We examined behavioral and gene expression changes after repetitive mild TBI followed by simultaneous treatment with both factors. We used a repetitive closed head injury of mice involving five injuries with a one-week interval between each TBI. We found that memory performance was significantly reduced by the injuries, unless the TBIs were followed by the tBHQ and pioglitazone administrations. Certain genes, e.g., growth hormone and osteopontin, were downregulated by the injury and this was reversed by the treatment while other genes, e.g., a tumor necrosis factor receptor, were upregulated by the injury and restored if the post-injury treatment was administered. Analysis of gene expression levels affected by the injury and/or the treatment point to potential mechanisms that could be exploited therapeutically.We perceive objects as permanent and stable despite frequent occlusions and eye movements, but their representation in the visual cortex is neither permanent nor stable Feature selective cells respond only as long as objects are visible, and their responses depend on eye position. We explored the hypothesis that the system maintains object pointers that provide permanence and stability. Pointers should send facilitatory signals to the feature cells of an object, and these signals should persist across temporary occlusions and remap to compensate for image displacements caused by saccades. Here we searched for such signals in monkey areas V2 and V4 (Macaca mulatta). We developed a new paradigm in which a monkey freely inspects an array of objects in search for reward while some of the objects are being occluded temporarily by opaque drifting strips. Two types of objects were used to manipulate attention. Results (1) Eye movements indicated a robust representation of location and type of the occluded objects; (2) in neurons of V4, but not V2, occluded objects produced elevated activity relative to blank condition; (3) the elevation of activity was reduced for objects that had been fixated immediately before the current fixation ('inhibition of return'); (4) when attended, or when target of a saccade, visible objects produced enhanced responses in V4, but occluded objects produced no modulation. While results 1-3 confirm the hypothesis, the absence of modulation under occlusion is not consistent. Further experiments are needed to resolve this discrepancy.