The Gravity Recovery and Climate Experiment (GRACE) twin satellites observe time variations in Earth's gravity field which yield valuable information about changes in terrestrial water storage (TWS). GRACE is characterized by low spatial (>150,000 km2) and temporal (>10 days) resolution but has the unique ability to sense water stored at all levels (including groundwater) systematically and continuously. The GRACE Data Assimilation System (DAS), based on the Catchment Land Surface Model (CLSM), enhances the value of the GRACE water storage data by enabling spatial and temporal downscaling and vertical decomposition into moisture components (i.e., groundwater, soil moisture, and snow), which individually are more useful for scientific applications. In this study, GRACE DAS was applied to North America, and GRACE‐based drought indicators were developed as part of a larger effort to investigate the possibility of more comprehensive and objective identification of drought conditions by integrating spatially, temporally, and vertically disaggregated GRACE data into the U.S. and North American Drought Monitors. Previously, the drought monitors lacked objective information on deep soil moisture and groundwater conditions, which are useful indicators of drought. Extensive data sets of groundwater storage from U.S. Geological Survey monitoring wells and soil moisture from the Soil Climate Analysis Network were used to assess improvements in the hydrological modeling skill resulting from the assimilation of GRACE TWS data. The results point toward modest, but statistically significant, improvements in the hydrological modeling skill across major parts of the United States, highlighting the potential value of a GRACE‐assimilated water storage field for improving drought detection.

The peroxisome proliferator activated receptor (PPAR)-γ is a nuclear receptor that is activated by lipids to induce the expression of genes involved in lipid and glucose metabolism, thereby converting nutritional signals into metabolic consequences1. PPARγ is the target of the thiazolidinedione (TZD)-class of insulin-sensitizing drugs, which have been widely prescribed to treat Type 2 Diabetes Mellitus (T2DM). A common side effect of treatment with TZDs is weight gain2. Here we report a novel role for central nervous system (CNS) PPARγ in the regulation of energy balance. We found that both acute and chronic activation of CNS PPARγ, by TZDs or by hypothalamic over-expression of a VP16-PPARγ fusion protein, led to positive energy balance in rats. Blocking the endogenous activation of CNS PPARγ, with pharmacological antagonists or with shRNA, led to negative energy balance, restored leptin-sensitivity in high-fat diet (HFD)-fed rats, and blocked the hyperphagic response to oral TZD treatment. These findings have implications for the widespread clinical use of TZD drugs and for understanding the etiology of diet-induced obesity.

Summary Glucagon-like peptide 1 (GLP-1) is necessary for normal gluco-regulation, and it has been widely presumed that this function reflects the actions of GLP-1 released from enteroendocrine L-cells. To test the relative importance of intestinal vs. pancreatic sources of GLP-1 for physiological regulation of glucose, we administered a GLP-1R antagonist, exendin 9–39 (Ex9), to mice with tissue-specific reactivation of the preproglucagon gene (Gcg). Ex9 impaired glucose tolerance in wild-type mice but had no impact on Gcg null or GLP-1R KO mice suggesting that Ex9 is a true and specific GLP-1R antagonist. Unexpectedly, Ex-9 had no effect on blood glucose in mice with restoration of intestinal Gcg. In contrast, pancreatic reactivation of Gcg fully restored the effect of Ex9 to impair both oral and IP glucose tolerance. These findings suggest an alternative model whereby islet GLP-1 also plays an important role in regulating glucose homeostasis.

Glucagon-like peptide 1 (GLP-1) is a peptide hormone that is released from the gut in response to nutrient ingestion and that has a range of metabolic effects, including enhancing insulin secretion and decreasing food intake. Postprandial GLP-1 secretion is greatly enhanced in rats and humans after some bariatric procedures, including vertical sleeve gastrectomy (VSG), and has been widely hypothesized to contribute to reduced intake, weight loss, and the improvements in glucose homeostasis after VSG. We tested this hypothesis using two separate models of GLP-1 receptor deficiency. We found that VSG-operated GLP-1 receptor–deficient mice responded similarly to wild-type controls in terms of body weight and body fat loss, improved glucose tolerance, food intake reduction, and altered food selection. These data demonstrate that GLP-1 receptor activity is not necessary for the metabolic improvements induced by VSG surgery.

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Severe cases of coronavirus disease 2019 (COVID-19) cannot be adequately managed with mechanical ventilation alone. The role and outcome of extracorporeal membrane oxygenation (ECMO) in the management of COVID-19 is currently unclear. Eight COVID-19 patients have received ECMO support in Shanghai with seven with venovenous (VV) ECMO support and one veno arterial (VA) ECMO during cardiopulmonary resuscitation. As of March 25, 2020, four patients died (50% mortality), three patients (37.5%) were successfully weaned off ECMO after 22, 40, and 47 days support, respectively, but remain on mechanical ventilation. One patient is still on VV ECMO with mechanical ventilation. The partial pressure of oxygen/fractional of inspired oxygen ratio before ECMO initiation was between 54 and 76, and all were well below 100. The duration of mechanical ventilation before ECMO ranged from 4 to 21 days. Except the one emergent VA ECMO during cardiopulmonary resuscitation, other patients were on ECMO support for between 18 and 47 days. In conclusion, ensuring effective, timely, and safe ECMO support in COVID-19 is key to improving clinical outcomes. Extracorporeal membrane oxygenation support might be an integral part of the critical care provided for COVID-19 patients in centers with advanced ECMO expertise.

The scarcity of groundwater storage change data at the global scale hinders our ability to monitor groundwater resources effectively. In this study, we assimilate a state‐of‐the‐art terrestrial water storage product derived from Gravity Recovery and Climate Experiment (GRACE) satellite observations into NASA's Catchment land surface model (CLSM) at the global scale, with the goal of generating groundwater storage time series that are useful for drought monitoring and other applications. Evaluation using in situ data from nearly 4,000 wells shows that GRACE data assimilation improves the simulation of groundwater, with estimation errors reduced by 36% and 10% and correlation improved by 16% and 22% at the regional and point scales, respectively. The biggest improvements are observed in regions with large interannual variability in precipitation, where simulated groundwater responds too strongly to changes in atmospheric forcing. The positive impacts of GRACE data assimilation are further demonstrated using observed low‐flow data. CLSM and GRACE data assimilation performance is also examined across different permeability categories. The evaluation reveals that GRACE data assimilation fails to compensate for the lack of a groundwater withdrawal scheme in CLSM when it comes to simulating realistic groundwater variations in regions with intensive groundwater abstraction. CLSM‐simulated groundwater correlates strongly with 12‐month precipitation anomalies in low‐latitude and midlatitude areas. A groundwater drought indicator based on GRACE data assimilation generally agrees with other regional‐scale drought indicators, with discrepancies mainly in their estimated drought severity.

SUMMARY Glucagon-like peptide-1 (GLP-1), an insulinotropic peptide released from the intestine after eating, is essential for normal glucose tolerance (GT). To determine whether this effect is mediated directly by GLP-1 receptors (GLP1R) on islet β-cells, we developed mice with β-cell specific knockdown of Glp1r. β-cell Glp1r knockdown mice had impaired GT after intraperitoneal (IP) glucose, and did not secrete insulin in response to IP or intravenous GLP-1. However, they had normal GT after oral glucose, a response that was impaired by a GLP1R antagonist. β-cell Glp1r knockdown mice had blunted responses to a GLP1R agonist, but intact glucose lowering with a DPP-4 inhibitor. Thus, in mice, β-cell Glp1r are required to respond to hyperglycemia and exogenous GLP-1, but other factors compensate for reduced GLP-1 action on the β-cell during meal ingestion. These results support a role for extra-islet GLP1R in oral glucose tolerance and paracrine regulation of β-cells by islet GLP-1.