Apyrase treatment prevents ischemia–reperfusion injury in rat lung isografts

ObjectiveEndothelial cells express the ectoenzyme ectonucleoside adenosine triphosphate diphosphohydrolase, an apyrase that inhibits vascular inflammation by catalyzing the hydrolysis of adenosine triphosphate and adenosine diphosphate. However, ectonucleoside adenosine triphosphate diphosphohydrolase expression is rapidly lost following oxidative stress, leading to the potential for adenosine triphosphate and related purigenic nucleotides to exacerbate acute solid organ inflammation and injury. We asked if administration of a soluble recombinant apyrase APT102 attenuates lung graft injury in a cold ischemia reperfusion model of rat syngeneic orthotopic lung transplantation.MethodsMale Fisher 344 donor lungs were cold preserved in a low-potassium dextrose solution in the presence or absence of APT102 for 18 hours prior to transplantation into syngeneic male Fisher 344 recipients. Seven minutes after reperfusion, lung transplant recipients received either a bolus of APT102 or vehicle (saline solution). Four hours after reperfusion, APT102- and saline solution–treated groups were evaluated for lung graft function and inflammation.ResultsAPT102 significantly reduced lung graft extracellular pools of adenosine triphosphate and adenosine diphosphate, improved oxygenation, and protected against pulmonary edema. Apyrase treatment was associated with attenuated neutrophil graft sequestration and less evidence of tissue inflammation as assessed by myeloperoxidase activity, expression of proinflammatory mediators, and numbers of apoptotic endothelial cells.ConclusionsAdministration of a soluble recombinant apyrase promotes lung function and limits the tissue damage induced by prolonged cold storage, indicating that extracellular purigenic nucleotides play a key role in promoting ischemia–reperfusion injury following lung transplantation

Manipulating the 3D organization of the largest synthetic yeast chromosome

Whether synthetic genomes can power life has attracted broad interest in the synthetic biology field. Here, we report de novo synthesis of the largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp yeast chromosome resulting from extensive genome streamlining and modification. We developed megachunk assembly combined with a hierarchical integration strategy, which significantly increased the accuracy and flexibility of synthetic chromosome construction. Besides the drastic sequence changes, we further manipulated the 3D structure of synIV to explore spatial gene regulation. Surprisingly, we found few gene expression changes, suggesting that positioning inside the yeast nucleoplasm plays a minor role in gene regulation. Lastly, we tethered synIV to the inner nuclear membrane via its hundreds of loxPsym sites and observed transcriptional repression of the entire chromosome, demonstrating chromosome-wide transcription manipulation without changing the DNA sequences. Our manipulation of the spatial structure of synIV sheds light on higher-order architectural design of the synthetic genomes. </p

Photometric Properties of Jupiter Trojans Detected by the Dark Energy Survey

The Jupiter Trojans are a large group of asteroids that are coorbiting with Jupiter near its L4 and L5 Lagrange points. The study of Jupiter Trojans is crucial for testing different models of planet formation that are directly related to our understanding of solar system evolution. In this work, we select known Jupiter Trojans listed by the Minor Planet Center from the full six years data set (Y6) of the Dark Energy Survey (DES) to analyze their photometric properties. The DES data allow us to study Jupiter Trojans with a fainter magnitude limit than previous studies in a homogeneous survey with griz band measurements. We extract a final catalog of 573 unique Jupiter Trojans. Our sample include 547 asteroids belonging to L5. This is one of the largest analyzed samples for this group. By comparing with the data reported by other surveys we found that the color distribution of L5 Trojans is similar to that of L4 Trojans. We find that L5 Trojans' g - i and g - r colors become less red with fainter absolute magnitudes, a trend also seen in L4 Trojans. Both the L4 and L5 clouds consistently show such a color-size correlation over an absolute magnitude range 11 < H < 18. We also use DES colors to perform taxonomic classifications. C- and P-type asteroids outnumber D-type asteroids in the L5 Trojans DES sample, which have diameters in the 5-20 km range. This is consistent with the color-size correlation

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages