Effects of ouabain on vascular reactivity

Ouabain is an endogenous substance occurring in the plasma in the nanomolar range, that has been proposed to increase vascular resistance and induce hypertension. This substance acts on the a-subunit of Na+,K+-ATPase inhibiting the Na+-pump activity. In the vascular smooth muscle this effect leads to intracellular Na+ accumulation that reduces the activity of the Na+/Ca2+ exchanger and to an increased vascular tone. It was also suggested that circulating ouabain, even in the nanomolar range, sensitizes the vascular smooth muscle to vasopressor substances. We tested the latter hypothesis by studying the effects of ouabain in the micromolar and nanomolar range on phenylephrine (PE)-evoked pressor responses. The experiments were performed in normotensive and hypertensive rats in vivo, under anesthesia, and in perfused rat tail vascular beds. The results showed that ouabain pretreatment increased the vasopressor responses to PE in vitro and in vivo. This sensitization after ouabain treatment was also observed in hypertensive animals which presented an enhanced vasopressor response to PE in comparison to normotensive animals. It is suggested that ouabain at nanomolar concentrations can sensitize vascular smooth muscle to vasopressor stimuli possibly contributing to increased tone in hypertension

Building Partnerships to Address Social and Technological Challenges to Enhance Farm Profitability and Improve Water Quality Through Better Grassland Management

With 2.1 million acres of pastureland and 1.25 million acres of hay land in Virginia, the rural Virginia landscape is predominately grassland. These lands form the base of the $3.96 billion-dollar livestock and dairy industry in Virginia. Managing these livestock in a profitable manner for farmers and beneficial to the environment is important. A cultural tradition with roots in colonial times has been to run animals in large fields year-round throughout Virginia. Livestock often graze from spring until fall (about 220 days), and farmers feed hay the remainder of the year. Spikes in the cost of fuel, fertilizer, and equipment are making traditional grazing/haying systems less profitable. The Virginia Cooperative Extension Farm Enterprise budgets show that that the cost of hay accounts for over 50$75 per cow by extending their grazing season. The same phenomenon applies to other types of grazing livestock. If ten percent of the livestock producers in the state adopted better grazing management to extend their grazing season by 60 days, profitability is expected for Virginia grazing livestock producers by over $5 million per year. Practices such as rotational grazing and stream exclusion are directly tied to National and State goals to improve water quality in the Chesapeake Bay. Virginia’s Phase III WIP (Chesapeake Bay Watershed Improvement Plan) seeks the exclusion of livestock from all perennial streams and achieving good rotational grazing practices on 347,000 acres of pasture. A number of agencies and private sector groups have been providing cost share and technical guidance to incentivize livestock stream exclusion and the installation of pasture management infrastructure. Installation is only part of the challenge. Farmers also need to be taught how to how to manage the system in a profitable manner and have been slow to adopt good pasture management practices. Preliminary data show that 87% of Virginia’s cow-calf producers manage their grasslands using traditional methods. Only six percent have extended their grazing season beyond 265 days

The Small Satellite-Based, Imaging X-Ray Polarimeter Explorer (IXPE) Mission

The Imaging X-ray Polarimeter Explorer (IXPE) focuses on high energy astrophysics in the 2—8 keV x-ray band. IXPE is designed to explore general relativistic and quantum physics effects of gravity, energy, electric and magnetic fields at extreme limits. IXPE, a NASA Small Explorer (SMEX) Mission, will add new dimensions to on-orbit x-ray science: polarization degree, polarization angle and extended object polarization imaging. Polarization uniquely probes physical anisotropies that are not otherwise measurable—ordered magnetic fields, aspheric matter distributions, or general relativistic coupling to black-hole spin. Detailed imaging enables the specific properties of extended x-ray sources to be differentiated. The IXPE Observatory consists of spacecraft and payload modules built up in parallel to form the Observatory during system integration and test. The payload includes three polarization-sensitive, x-ray detector arrays paired with three x-ray mirror module assemblies (MMA). A deployable boom provides the correct separation (focal length) between the detector units and MMAs. Currently, the boom has been delivered, all four detectors units (DU) are complete, the detectors service unit (DSU) is complete, instrument system testing has been completed (DSU with 3 DUs), three of four MMAs is built and all spacecraft components except the solar array have been delivered along with the spacecraft and payload structures. Payload and spacecraft integration and test (I&T) started in March 2020. This paper overviews the flight segment (the Observatory, payload, and spacecraft implementation concepts) with emphasis on the build status and summarizes the launch segment. Launch is planned to occur on a Falcon 9 launch vehicle during Summer 2021. The paper summarizes the impacts of switching from the ‘design-to baseline’ of Pegasus XL to the selected launch vehicle for flight, Falcon 9. COVID-19 impacts to the Project are also summarized. The paper will close with a summary of the mission development status. The Project is firmly into the build phase for both the spacecraft and payload and rapidly approaching Observatory I&T

In vitro and in vivo mRNA delivery using lipid-enveloped pHresponsive polymer nanoparticles

Biodegradable core−shell structured nanoparticles with a poly(β-amino ester) (PBAE) core enveloped by a phospholipid bilayer shell were developed for in vivo mRNA delivery with a view toward delivery of mRNA-based vaccines. The pH-responsive PBAE component was chosen to promote endosome disruption, while the lipid surface layer was selected to minimize toxicity of the polycation core. Messenger RNA was efficiently adsorbed via electrostatic interactions onto the surface of these net positively charged nanoparticles. In vitro, mRNA-loaded particle uptake by dendritic cells led to mRNA delivery into the cytosol with low cytotoxicity, followed by translation of the encoded protein in these difficult-to-transfect cells at a frequency of 30%. Particles loaded with mRNA administered intranasally (i.n.) in mice led to the expression of the reporter protein luciferase in vivo as soon as 6 h after administration, a time point when naked mRNA given i.n. showed no expression. At later time points, luciferase expression was detected in naked mRNA-treated mice, but this group showed a wide variation in levels of transfection, compared to particle-treated mice. This system may thus be promising for noninvasive delivery of mRNA-based vaccines.United States. Dept. of Defense (Institute for Soldier Nanotechnology, contract W911NF-07-D-0004)Ragon Institute of MGH, MIT and HarvardSingapore. Agency for Science, Technology and ResearchHoward Hughes Medical Institute (Investigator

Deep Sequencing the Transcriptome Reveals Seasonal Adaptive Mechanisms in a Hibernating Mammal

Mammalian hibernation is a complex phenotype involving metabolic rate reduction, bradycardia, profound hypothermia, and a reliance on stored fat that allows the animal to survive for months without food in a state of suspended animation. To determine the genes responsible for this phenotype in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) we used the Roche 454 platform to sequence mRNA isolated at six points throughout the year from three key tissues: heart, skeletal muscle, and white adipose tissue (WAT). Deep sequencing generated approximately 3.7 million cDNA reads from 18 samples (6 time points ×3 tissues) with a mean read length of 335 bases. Of these, 3,125,337 reads were assembled into 140,703 contigs. Approximately 90% of all sequences were matched to proteins in the human UniProt database. The total number of distinct human proteins matched by ground squirrel transcripts was 13,637 for heart, 12,496 for skeletal muscle, and 14,351 for WAT. Extensive mitochondrial RNA sequences enabled a novel approach of using the transcriptome to construct the complete mitochondrial genome for I. tridecemlineatus. Seasonal and activity-specific changes in mRNA levels that met our stringent false discovery rate cutoff (1.0×10−11) were used to identify patterns of gene expression involving various aspects of the hibernation phenotype. Among these patterns are differentially expressed genes encoding heart proteins AT1A1, NAC1 and RYR2 controlling ion transport required for contraction and relaxation at low body temperatures. Abundant RNAs in skeletal muscle coding ubiquitin pathway proteins ASB2, UBC and DDB1 peak in October, suggesting an increase in muscle proteolysis. Finally, genes in WAT that encode proteins involved in lipogenesis (ACOD, FABP4) are highly expressed in August, but gradually decline in expression during the seasonal transition to lipolysis

Different Drivers: Exploring employee involvement in corporate philanthropy

Corporate Philanthropy (CP) is multi-dimensional, differs between sectors and involves both individual and organizational decision-making to achieve business and social goals. However, the CP literature characteristically focuses on strategic decisions made by business leaders and ignores the role of employees, especially those in lower status and lower paid positions. To redress this imbalance, we conducted a qualitative study of employees’ involvement in CP processes in ten workplaces in the South East of England to identify whether and how they are involved in CP decision-making and to capture their perspective on the nature of CP and the benefits generated by such activities. We specifically chose to study workplaces where employees are involved in the actual execution of the CP strategy, prioritising companies with a visible presence on the high street. The results illustrate the benefits of involving employees in CP decision-making, which we argue derives in part from the ‘liminal-like states’ that typify CP activities organised by shop floor staff, involving the temporary overturning of hierarchies, humanising of workplaces and opportunities for lower-level staff to prioritise their personal philanthropic preferences and signal their charitable identity to colleagues and customers. Whilst the data also suggests that CP decision-making remains predominantly top-down and driven by profit-oriented goals, we conclude that employees should be involved in choosing charitable causes as well as in designing and implementing workplace fundraising, in order to maximise the advantages of CP for the company and for wider society

Compartment-Restricted Biotinylation Reveals Novel Features of Prion Protein Metabolism in Vivo

A selective tagging method for detecting minor alternatively-localized populations of a protein is used to study a disease-associated transmembrane form of prion protein. The analysis reveals key features of transmembrane prion protein metabolism and one way this is altered by human disease-causing mutants

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems

New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous WIA in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little, while not much new information has been gathered on soil organisms. The impact on marine coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal classneonicotinoids and fipronil. , withContinued large scale – mostly prophylactic – use of these persistent organochlorine pesticides has the potential to greatly decreasecompletely eliminate populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates, and their deleterious impacts on growth, reproduction and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al. 2015)