Na+ influx and Na+-K+ pump activation during short-term exposure of cardiac myocytes to aldosterone

To examine the effect of aldosterone on sarcolemmalNa⁺ transport, we measuredouabain-sensitive electrogenicNa⁺-K⁺pump current(I_p) involtage-clamped ventricular myocytes and intracellularNa⁺ activity(aⁱ_Na) in right ventricularpapillary muscles. Aldosterone (10 nM) induced an increase in bothI_p and the rateof rise of aⁱ_Na duringNa⁺-K⁺pump blockade with the fast-acting cardiac steroid dihydroouabain. Thealdosterone-induced increase inI_p and rate ofrise of aⁱ_Na was eliminated bybumetanide, suggesting that aldosterone activates Na⁺ influx through theNa⁺-K⁺-2Clcotransporter. To obtain independent support for this, theNa⁺,K⁺, andCl concentrations in thesuperfusate and solution of pipettes used to voltage clamp myocyteswere set at levels designed to abolish the inward electrochemicaldriving force for theNa⁺-K⁺-2Clcotransporter. This eliminated the aldosterone-induced increase inI_p. We concludethat in vitro exposure of cardiac myocytes to aldosterone activates theNa⁺-K⁺-2Clcotransporter to enhance Na⁺influx and stimulate theNa⁺-K⁺pump.

     

Body composition and cardiometabolic health across the menopause transition

Every year, 2 million women reach menopause in the United States, and they may spend 40% or more of their life in a postmenopausal state. In the years immediately preceding menopause—known as the menopause transition (or perimenopause)—changes in hormones and body composition increase a woman’s overall cardiometabolic risk. In this narrative review, we summarize the changes in weight, body composition, and body fat distribution, as well as the changes in energy intake, energy expenditure, and other cardiometabolic risk factors (lipid profile, glucose metabolism, sleep health, and vascular function), that occur during the menopause transition. We also discuss the benefits of lifestyle interventions in women in the earlier stages of menopause before these detrimental changes occur. Finally, we discuss how to include perimenopausal women in research studies so that women across the life-span are adequately represented.     

Cryptic genetic structure and copy-number variation in the ubiquitous forest symbiotic fungus Cenococcum geophilum

Ectomycorrhizal (ECM) fungi associated with plants constitute one of the most successful symbiotic interactions in forest ecosystems. ECM support trophic exchanges with host plants and are important factors for the survival and stress resilience of trees. However, ECM clades often harbour morpho-species and cryptic lineages, with weak morphological differentiation. How this relates to intraspecific genome variability and ecological functioning is poorly known. Here, we analysed 16 European isolates of the ascomycete Cenococcum geophilum, an extremely ubiquitous forest symbiotic fungus with no known sexual or asexual spore-forming structures but with a massively enlarged genome. We carried out whole-genome sequencing to identify single-nucleotide polymorphisms. We found no geographic structure at the European scale but divergent lineages within sampling sites. Evidence for recombination was restricted to specific cryptic lineages. Lineage differentiation was supported by extensive copy-number variation. Finally, we confirmed heterothallism with a single MAT1 idiomorph per genome. Synteny analyses of the MAT1 locus revealed substantial rearrangements and a pseudogene of the opposite MAT1 idiomorph. Our study provides the first evidence for substantial genome-wide structural variation, lineage-specific recombination and low continent-wide genetic differentiation in C. geophilum. Our study provides a foundation for targeted analyses of intra-specific functional variation in this major symbiosis.     

Herpes Simplex Virus type 1 infects Langerhans cells and the novel epidermal dendritic cell,Epi-cDC2s,via different entry pathways

Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is closely related to dermal conventional dendritic cells type 2 (cDC2) and can be preferentially infected by HIV. Here we show that in epidermal explants topically infected with herpes simplex virus (HSV-1), both LCs and Epi-cDC2s interact with HSV-1 particles and infected keratinocytes. Isolated Epi-cDC2s support higher levels of infection than LCs in vitro, inhibited by acyclovir, but both MNP subtypes express similar levels of the HSV entry receptors nectin-1 and HVEM, and show similar levels of initial uptake. Using inhibitors of endosomal acidification, actin and cholesterol, we found that HSV-1 utilises different entry pathways in each cell type. HSV-1 predominantly infects LCs, and monocyte-derived MNPs, via a pH-dependent pathway. In contrast, Epi-cDC2s are mainly infected via a pH-independent pathway which may contribute to the enhanced infection of Epi-cDC2s. Both cells underwent apoptosis suggesting that Epi-cDC2s may follow the same dermal migration and uptake by dermal MNPs that we have previously shown for LCs. Thus, we hypothesize that the uptake of HSV and infection of Epi-cDC2s will stimulate immune responses via a different pathway to LCs, which in future may help guide HSV vaccine development and adjuvant targeting.     

Development of Commercially Acceptable Formulations of the Nematophagous FungusVerticillium chlamydosporium

Studies in shaken flasks and a 20-liter bioreactor showed that biomass ofVerticillium chlamydosporiumcould be produced in large quantities in liquid culture. The fungus grew readily in media containing commercially available, low-cost ingredients (e.g., cotton seed meal, soybean meal) and a volumetric productivity of about 0.3 g/h/liter was achieved in the bioreactor. Chlamydospores were not produced in submerged culture, the biomass consisting only of mycelia and conidia. When this biomass was mixed with a carrier (kaolin) and a binder (gum arabic) and the ingredients were granulated and then dried to a moisture content of less than 2%, a biologically active product suitable for application to soil was produced. The fungus grew vigorously from these granules when they were placed on agar and retained its viability when granules were stored in vacuum-sealed bags at 25°C for 12 months. Experiments on tomato in the glasshouse showed that when the formulated product was incorporated into field soil at 10 g granules/liter soil, population densities ofV. chlamydosporiumwere increased to about 10⁴colony-forming units/g soil after 7–14 weeks. Between 37 and 82% of the first generation egg masses produced byMeloidogyne javanicacontained parasitized eggs.     

Farthest north lake and fjord populations of calanoid copepods Limnocalanus macrurus and Drepanopus bungei in the Canadian high Arctic

The zooplankton assemblages of Lake A and Disraeli Fjord, northern Ellesmere Island (83°N, 75°W), were surveyed in early summer 1999. In permanently ice-covered Lake A, two glacial relict calanoid copepod species (Drepanopus bungei and Limnocalanus macrurus) were found in the top 30 m. All developmental stages of the more abundant D. bungei were present, whereas only adults of L. macrurus were found. Analysis of gut contents showed that L. macrurus preyed upon the smaller species. A net tow sample of zooplankton from Disraeli Fjord was mainly composed of D. bungei and L. macrurus, along with two marine cyclopoid copepods (Oncaea borealis and Oithona similis). These two zooplankton communities occur within unusual environments that are strongly influenced by perennial ice and snow. They will be subject to major habitat disruption should the current warming trends continue in the north polar region.     

What to do in the face of multiple threats? Incorporating dependencies within a return on investment framework for conservation

Aim Our study aimed to determine priority areas for conservation investment with explicit consideration of the impacts of multiple threatening processes, and the dependencies that exist between actions required to abate these threats. Location Australia. Methods We analysed the return on investment for two different management actions aimed at reducing the impact of invasive species on the native fauna and flora of Australia. We focussed on the management of the European red fox (Vulpes vulpes) and European rabbit (Oryctolagus cuniculus) at two spatial scales: across 72 biogeographic regions of Australia and within one high‐priority biogeographic region. We considered each action independently and also explicitly accounted for the option of an integrated fox and rabbit management action. We accounted for the spatial distributions of the threatened species within our analysis and determined how this refined spatial information influenced both the priority areas and the timing of this investment. Results Integrated fox and rabbit management was identified as a higher priority than singular threat abatement in most bioregions, whereas rabbit control alone was the most frequent priority if dependencies between actions were ignored. At the regional scale, funding was entirely directed to integrated action when seven or more species within the priority region were impacted by more than one threat. The total allocation of funding and timing of initial investment remained relatively insensitive to differences in the spatial overlap of species distributions. Main conclusions Our findings indicate that prioritizing conservation actions without explicit consideration of the impacts of multiple threats can reduce the cost‐effectiveness of investments. The benefits expected from investment in abating one threat alone may be overestimated where other processes continue to threaten species persistence. We conclude that future attention should be directed to refining our understanding of the cost‐efficiencies delivered through integrated actions and institutional mechanisms to achieve their delivery.     

Evidence for Systemic, Cross-resistance in White Clover ( Trifolium repens ) and Annual Medic ( Medicago truncatula var truncatula ) Induced by Biological and Chemical Agents

Soil-based growth cabinet and greenhouse experiments were designed to determine whether a resistance response previously noted in Trifolium repens to the clover cyst nematode Heterodera trifolii was systemic and also effective against a pest from a different taxon. Root applications of benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester (BTH) or a Pseudomonas -like bacterial strain P29 to white clover seedlings induced resistance to the blue-green aphid, Acyrthosiphon kondoi . A similar response was observed in the annual medic, Medicago truncatula var truncatula . Estimation of lignin and callose content of whole plants at the termination of the bioassay showed no differences between treated and control plants. The significance of these findings is discussed.