Effect of Perfusate Osmolarity on Hearts Preserved Under Hypothermic Pulsatile Perfusion for 24 Hours

Canine hearts preserved under hypothermic pulsatile perfusion (24 hours) with an osmolarity of 340 mOsm/L had better preservation and transplantation response than hearts perfused at an osmolarity of 310 and 270 mOsm/L. The hearts perfused at 340 mOsm /L survived an average of 22.6 days after transplantation. This survival was significantly (p\u3e0.05) better than that observed after fresh transplantation (13.4 days average). Hearts perfused at 270 mOsm /L had a significantly (p\u3e0.05) lower survival after transplantation (5.8 days average) than the fresh allografts or the hearts perfused at 310 or 340 mOsm / L. Similar survival times were observed for the fresh transplants and those perfused at an osmolarity of 310 mOsm/L (17.8 days average). Thus, osmolarity appears to be an essential factor for hypothermic pulsatile perfusion of hearts

Meeting the Challenges Facing Wheat Production The Strategic Research Agenda of the Global Wheat Initiative

Wheat occupies a special role in global food security since, in addition to providing 20% of our carbohydrates and protein, almost 25% of the global production is traded internationally. The importance of wheat for food security was recognised by the Chief Agricultural Scientists of the G20 group of countries when they endorsed the establishment of the Wheat Initiative in 2011. The Wheat Initiative was tasked with supporting the wheat research community by facilitating col-laboration, information and resource sharing and helping to build the capacity to address chal-lenges facing production in an increasingly variable environment. Many countries invest in wheat research. Innovations in wheat breeding and agronomy have delivered enormous gains over the past few decades, with the average global yield increasing from just over 1 tonne per hectare in the early 1960s to around 3.5 tonnes in the past decade. These gains are threatened by climate change, the rapidly rising financial and environmental costs of fertilizer, and pesticides, combined with declines in water availability for irrigation in many regions. The international wheat research community has worked to identify major opportunities to help ensure that global wheat pro-duction can meet demand. The outcomes of these discussions are presented in this paper

A small molecule MST1/2 inhibitor accelerates murine liver regeneration with improved survival in models of steatohepatitis

Dysfunctional liver regeneration following surgical resection remains a major cause of postoperative mortality and has no therapeutic options. Without targeted therapies, the current treatment paradigm relies on supportive therapy until homeostasis can be achieved. Pharmacologic acceleration of regeneration represents an alternative therapeutic avenue. Therefore, we aimed to generate a small molecule inhibitor that could accelerate liver regeneration with an emphasis on diseased models, which represent a significant portion of patients who require surgical resection and are often not studied. Utilizing a clinically approved small molecule inhibitor as a parent compound, standard medicinal chemistry approaches were utilized to generate a small molecule inhibitor targeting serine/threonine kinase 4/3 (MST1/2) with reduced off-target effects. This compound, mCLC846, was then applied to preclinical models of murine partial hepatectomy, which included models of diet-induced metabolic dysfunction-associated steatohepatitis (MASH). mCLC846 demonstrated on target inhibition of MST1/2 and reduced epidermal growth factor receptor inhibition. The inhibitory effects resulted in restored pancreatic beta-cell function and survival under diabetogenic conditions. Liver-specific cell-line exposure resulted in Yes-associated protein activation. Oral delivery of mCLC846 perioperatively resulted in accelerated murine liver regeneration and improved survival in diet-induced MASH models. Bulk transcriptional analysis of regenerating liver remnants suggested that mCLC846 enhanced the normal regenerative pathways and induced them following liver resection. Overall, pharmacological acceleration of liver regeneration with mCLC846 was feasible, had an acceptable therapeutic index, and provided a survival benefit in models of diet-induced MASH

Black Nature / Dark Matter Poetics: Camille Dungy’s Smith Blue and Tracy K. Smith’s Life on Mars

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