Relationship between Nest and Body Temperature and Microclimate in the Paper Wasp Polistes dominula.

The paper wasp Polistes dominula is a thermophilic species originating from the Mediterranean climate, but is now widely spread in Europe. They live in quite differing habitats; and as synanthropic species, they have been established in human settlement areas. They build a single small comb at protected places with a favorable microclimate. We measured the temperature of the wasps, the nests and their environment at typical nesting sides in Austria (Europe) in the temperate climate, in order to reveal relationships between nest and body temperature and the habitats' microclimate. The temperatures of the comb and of the wasps' body were in a wide range (~20-37 °C) above the ambient air temperature at the nest. This is an advantage as higher temperatures accelerate the development speed of the brood. However, the mean comb temperature did not exceed approximately 38.6 °C. This was managed by cooling efforts of the adult wasps. The ambient air temperature near the nest (~1-2 cm) was always clearly elevated above the ambient air temperature at a local standard weather station in the habitat. A comparison with climate-model-generated macroclimate data revealed the necessity of measuring microclimate data for a reliable description of the insects' thermal environment.

Effect of climate on strategies of nest and body temperature regulation in paper wasps, Polistes biglumis and Polistes gallicus.

Polistes paper wasps are a widespread taxon inhabiting various climates. They build nests in the open without a protective outer layer, which makes them vulnerable to changing temperatures. To better understand the options they have to react to environmental variation and climate change, we here compare the thermoregulatory behavior of Polistes biglumis from cool Alpine climate with Polistes gallicus from warm Mediterranean climate. Behavioral plasticity helps both of them to withstand environmental variation. P. biglumis builds the nests oriented toward east-south-east to gain solar heat of the morning sun. This increases the brood temperature considerably above the ambience, which speeds up brood development. P. gallicus, by contrast, mostly avoids nesting sites with direct insolation, which protects their brood from heat stress on hot days. To keep the brood temperature below 40-42 °C on warm days, the adults of the two species show differential use of their common cooling behaviors. While P. biglumis prefers fanning of cool ambient air onto the nest heated by the sun and additionally cools with water drops, P. gallicus prefers cooling with water drops because fanning of warm ambient air onto a warm nest would not cool it, and restricts fanning to nests heated by the sun.

JAK2-mutant hematopoietic cells display metabolic alterations that can be targeted to treat myeloproliferative neoplasms.

Increased energy requirement and metabolic reprogramming are hallmarks of cancer cells. We show that metabolic alterations in hematopoietic cells are fundamental to the pathogenesis of mutant JAK2-driven myeloproliferative neoplasms (MPNs). We found that expression of mutant JAK2 augmented and subverted metabolic activity of MPN cells, resulting in systemic metabolic changes in vivo, including hypoglycemia, adipose tissue atrophy, and early mortality. Hypoglycemia in MPN mouse models correlated with hyperactive erythropoiesis and was due to a combination of elevated glycolysis and increased oxidative phosphorylation. Modulating nutrient supply through high-fat diet improved survival, whereas high-glucose diet augmented the MPN phenotype. Transcriptomic and metabolomic analyses identified numerous metabolic nodes in JAK2-mutant hematopoietic stem and progenitor cells that were altered in comparison with wild-type controls. We studied the consequences of elevated levels of Pfkfb3, a key regulatory enzyme of glycolysis, and found that pharmacological inhibition of Pfkfb3 with the small molecule 3PO reversed hypoglycemia and reduced hematopoietic manifestations of MPNs. These effects were additive with the JAK1/2 inhibitor ruxolitinib in vivo and in vitro. Inhibition of glycolysis by 3PO altered the redox homeostasis, leading to accumulation of reactive oxygen species and augmented apoptosis rate. Our findings reveal the contribution of metabolic alterations to the pathogenesis of MPNs and suggest that metabolic dependencies of mutant cells represent vulnerabilities that can be targeted for treating MPNs.

Effectiveness and safety of moderate-intensity aerobic water exercise during pregnancy for reducing use of epidural analgesia during labor: protocol for a randomized clinical trial.

BACKGROUND: Epidural analgesia during labor can provide effective pain relief, but can also lead to adverse effects. The practice of moderate exercise during pregnancy is associated with an increased level of endorphins in the blood, and this could also provide pain relief during labor. Aerobic water exercises, rather than other forms of exercise, do not negatively impact articulations, reduce edema, blood pressure, and back pain, and increase diuresis. We propose a randomized controlled trial (RCT) to evaluate the effectiveness and safety of a moderate water exercise program during pregnancy on the need for epidural analgesia during labor. METHODS: A multi-center, parallel, randomized, evaluator blinded, controlled trial in a primary care setting. We will randomised 320 pregnant women (14 to 20 weeks gestation) who have low risk of complications to a moderate water exercise program or usual care. DISCUSSION: The findings of this research will contribute toward understanding of the effects of a physical exercise program on pain and the need for analgesia during labor. TRIAL REGISTRATION: ISRCTN Registry identifier: 14097513 register on 04 September 2017. Retrospectively registered.

Incidence of intracardiac thrombus formation prior to electrical cardioversion in respect to the mode of oral anticoagulation.

AIMS: To evaluate the incidence of newly diagnosed intracardiac thrombi (ICT) in respect to the mode of OAC in patients undergoing cardioversion (CV). METHODS AND RESULTS: We prospectively assessed transesophageal echocardiography (TEE) and OAC therapy prior to CV in AF patients with ≥48-hour duration scheduled for CV. A total of 60 first-time ICT (4.7%) were diagnosed in 1,286 TEE, with highest rate in patients without OAC (9.6% vs. OAC 4.1%, P  =  0.009) and an apparently lower rate in nonvitamin K antagonist anticoagulants (NOAC) therapy compared to vitamin K antagonist (VKA) (2.5% vs. 5.3%, P  =  0.02). VKA therapy control 4 weeks prior to CV was overall average (time in therapeutic range 60%) and patients showed more frequently clinical characteristics and TEE parameters associated with risk for ICT. Even among patients with effective OAC therapy (uninterrupted NOAC and VKA therapy with international normalized ratio (INR) ≥2.0 for 3 weeks), ICT occurred in 2.7%, but with no difference between both groups (P  =  0.22). There was no difference between different types of NOAC. Independent predictors for ICT were history of embolism, hypertension, BMI, absence of OAC, renal function, reduced atrial appendage flow, and presence of spontaneous echo contrast. CONCLUSION: NOAC therapy seems favorable in the overall prevention of ICT, although this is likely to be caused by suboptimal VKA therapy control and differences in the overall health status between VKA and NOAC patients. ICT occurred even with effective OAC therapy suggesting individual TEE-guided cardioversion in patients at risk.

Protective efficacy and safety of liver stage attenuated malaria parasites.

During the clinically silent liver stage of a Plasmodium infection the parasite replicates from a single sporozoite into thousands of merozoites. Infection of humans and rodents with large numbers of sporozoites that arrest their development within the liver can cause sterile protection from subsequent infections. Disruption of genes essential for liver stage development of rodent malaria parasites has yielded a number of attenuated parasite strains. A key question to this end is how increased attenuation relates to vaccine efficacy. Here, we generated rodent malaria parasite lines that arrest during liver stage development and probed the impact of multiple gene deletions on attenuation and protective efficacy. In contrast to P. berghei strain ANKA LISP2(-) or uis3(-) single knockout parasites, which occasionally caused breakthrough infections, the double mutant lacking both genes was completely attenuated even when high numbers of sporozoites were administered. However, different vaccination protocols showed that LISP2(-) parasites protected better than uis3(-) and double mutants. Hence, deletion of several genes can yield increased safety but might come at the cost of protective efficacy.

Actin regulation in the malaria parasite.

Many intracellular pathogens hijack host cell actin or its regulators for cell-to-cell spreading. In marked contrast, apicomplexan parasites, obligate intracellular, single cell eukaryotes that are phylogenetically older than the last common ancestor of animals and plants, employ their own actin cytoskeleton for active motility through tissues and invasion of host cells. A hallmark of actin-based motility of the malaria parasite is a minimal set of proteins that potentially regulate microfilament dynamics. An intriguing feature of the Plasmodium motor machinery is the virtual absence of elongated filamentous actin in vivo. Despite this unusual actin regulation sporozoites, the transmission stages that are injected into the mammalian host by Anopheles mosquitoes, display fast (1-3 µm/s) extracellular motility. Experimental genetics and analysis of recombinant proteins have recently contributed to clarify some of the cellular roles of apicomplexan actin monomer- and filament-binding proteins in parasite life cycle progression. These studies established that the malaria parasite employs multiple proteins that bind actin to form pools of readily polymerizable monomers, a prerequisite for fast formation of actin polymers. The motile extracellular stages of Plasmodium parasites are an excellent in vivo model system for functional characterization of actin regulation in single cell eukaryotes.