Exercise training reverses cardiac aging phenotypes associated with heart failure with preserved ejection fraction in male mice

Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age‐related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown. Given the strong association between aging and HFpEF, we hypothesized that ExT might reverse cardiac aging phenotypes that contribute to HFpEF pathophysiology and additionally provide a platform for novel mechanistic and therapeutic discovery. Here, we show that aged (24–30 months) C57BL/6 male mice recapitulate many of the hallmark features of HFpEF, including preserved left ventricular ejection fraction, subclinical systolic dysfunction, diastolic dysfunction, impaired cardiac reserves, exercise intolerance, and pathologic cardiac hypertrophy. Similar to older humans, ExT in old mice improved exercise capacity, diastolic function, and contractile reserves, while reducing pulmonary congestion. Interestingly, RNAseq of explanted hearts showed that ExT did not significantly modulate biological pathways targeted by conventional HF medications. However, it reversed multiple age‐related pathways, including the global downregulation of cell cycle pathways seen in aged hearts, which was associated with increased capillary density, but no effects on cardiac mass or fibrosis. Taken together, these data demonstrate that the aged C57BL/6 male mouse is a valuable model for studying the role of aging biology in HFpEF pathophysiology, and provide a molecular framework for how ExT potentially reverses cardiac aging phenotypes in HFpEF.     

Genetic diversity of the Plasmodium falciparum GTP-cyclohydrolase 1, dihydrofolate reductase and dihydropteroate synthetase genes reveals new insights into sulfadoxine-pyrimethamine antimalarial drug resistance

Plasmodium falciparum parasites resistant to antimalarial treatments have hindered malaria disease control. Sulfadoxine-pyrimethamine (SP) was used globally as a first-line treatment for malaria after wide-spread resistance to chloroquine emerged and, although replaced by artemisinin combinations, is currently used as intermittent preventive treatment of malaria in pregnancy and in young children as part of seasonal malaria chemoprophylaxis in sub-Saharan Africa. The emergence of SP-resistant parasites has been predominantly driven by cumulative build-up of mutations in the dihydrofolate reductase (pfdhfr) and dihydropteroate synthetase (pfdhps) genes, but additional amplifications in the folate pathway rate-limiting pfgch1 gene and promoter, have recently been described. However, the genetic make-up and prevalence of those amplifications is not fully understood. We analyse the whole genome sequence data of 4,134 P. falciparum isolates across 29 malaria endemic countries, and reveal that the pfgch1 gene and promoter amplifications have at least ten different forms, occurring collectively in 23% and 34% in Southeast Asian and African isolates, respectively. Amplifications are more likely to be present in isolates with a greater accumulation of pfdhfr and pfdhps substitutions (median of 1 additional mutations; P<0.00001), and there was evidence that the frequency of pfgch1 variants may be increasing in some African populations, presumably under the pressure of SP for chemoprophylaxis and anti-folate containing antibiotics used for the treatment of bacterial infections. The selection of P. falciparum with pfgch1 amplifications may enhance the fitness of parasites with pfdhfr and pfdhps substitutions, potentially threatening the efficacy of this regimen for prevention of malaria in vulnerable groups. Our work describes new pfgch1 amplifications that can be used to inform the surveillance of SP drug resistance, its prophylactic use, and future experimental work to understand functional mechanisms.     

Biological soil crust salvage for dryland restoration: an opportunity for natural resource restoration

Biocrusts' functional importance and vulnerability to disturbance have motivated consistent interest in biocrust restoration, as well as a recent increase in research to cultivate biocrusts in laboratory and greenhouse settings for use in ecological restoration. As part of a sustainable approach to developing biocrust restoration, we argue that a complementary step is to improve and accelerate methods for salvaging biocrusts that would otherwise be destroyed in a forthcoming disturbance. The increasing rate and scale of disturbance pressures in drylands where biocrusts flourish means that the supply of salvageable biocrust and demand for that material in restoration greatly exceed the present cultivable supply. In this article we describe the state of knowledge for biocrust salvage, present a simple set of steps for conducting a salvage harvest, discuss risks and benefits when considering using salvage, and suggest future research directions to facilitate scaling up biocrust restoration using salvaged material. A focus on the use of salvaged biocrust as a restoration source may prove an important step to improve ecological restoration in notoriously difficult to restore dryland ecosystems.     

Wading through the swamp: what does tropical peatland restoration mean to national‐level stakeholders in Indonesia?

Ecological restoration is considered to play an important role in mitigating climate change, protecting biodiversity, and preventing environmental degradation. Yet, there are often multiple perspectives on what outcomes restoration should be aiming to achieve, and how we should get to that point. In this study we interview a range of policymakers, academics, and non‐governmental organization (NGO) representatives to explore the range of perspectives on the restoration of Indonesia's tropical peatlands—key global ecosystems that have undergone large‐scale degradation. Thematic analysis suggests that participants agreed about the importance of restoration, but had differing opinions on how effective restoration activities to date have been and what a restored peatland landscape should look like. These results exemplify how ecological restoration can mean different things to different people, but also highlight important areas of consensus for moving forward with peatland restoration strategies.     

Plant respiration: Controlled by photosynthesis or biomass?

Two simplifying hypotheses have been proposed for whole‐plant respiration. One links respiration to photosynthesis; the other to biomass. Using a first‐principles carbon balance model with a prescribed live woody biomass turnover, applied at a forest research site where multidecadal measurements are available for comparison, we show that if turnover is fast the accumulation of respiring biomass is low and respiration depends primarily on photosynthesis; while if turnover is slow the accumulation of respiring biomass is high and respiration depends primarily on biomass. But the first scenario is inconsistent with evidence for substantial carry‐over of fixed carbon between years, while the second implies far too great an increase in respiration during stand development—leading to depleted carbohydrate reserves and an unrealistically high mortality risk. These two mutually incompatible hypotheses are thus both incorrect. Respiration is not linearly related either to photosynthesis or to biomass, but it is more strongly controlled by recent photosynthates (and reserve availability) than by total biomass.     

Cold and hungry: combined effects of low temperature and resource scarcity on an edge-of-range temperate primate,the golden snub-nose monkey

Both biotic and abiotic factors play important roles in influencing ecological distributions and niche limits. Where biotic and abiotic stressors co-occur in space and time, homeostatic systems face a scenario in which stressors can compound to impose a challenge that is greater than the sum of the separate factors. We studied the homeostatic strategies of the golden snub-nosed monkey Rhinopithecus roxellana, a species living in temperate deciduous forests at the edge of the global distribution range for folivorous primates, to cope with the co-occurrence of cold temperatures and resource scarcity during winter. We discovered that in winter the monkeys experience a dietary energy deficit of 101 kJ mbm⁻¹ d⁻¹ compared with calculated needs, despite increased feeding. This is partly offset by behavioral changes (reduced locomotion and increased resting) and reducing skin temperature by an average of 3.2°C through a cutaneous vasoconstriction to decrease heat loss. However, their major strategy is ingesting surplus energy and accumulating fat reserves when food was not limiting during summer and autumn. Their 14% of body mass lost over the winter represented an energy yield of 102 kJ mbm⁻¹ d⁻¹, which closely matched the calculated winter energy deficit of 101 kJ mbm⁻¹ d⁻¹. However, the latter value assumes that all the 75.41 kJ mbm⁻¹ d⁻¹ of protein ingested in winter was available for energy metabolism. This is almost certainly an over-estimate, suggesting that the study population was in negative energy balance over the study period. Our study therefore suggests that despite its suit of integrated homeostatic responses, the confluence of low temperatures and resource limitation during winter places this edge-of-range primate close the threshold of what is energetically viable. It also provides a framework for quantitative models predicting the vulnerability of temperate primates to global change.     

What would it take to describe the global diversity of parasites?

How many parasites are there on Earth? Here, we use helminth parasites to highlight how little is known about parasite diversity, and how insufficient our current approach will be to describe the full scope of life on Earth. Using the largest database of host–parasite associations and one of the world’s largest parasite collections, we estimate a global total of roughly 100 000–350 000 species of helminth endoparasites of vertebrates, of which 85–95% are unknown to science. The parasites of amphibians and reptiles remain the most poorly described, but the majority of undescribed species are probably parasites of birds and bony fish. Missing species are disproportionately likely to be smaller parasites of smaller hosts in undersampled countries. At current rates, it would take centuries to comprehensively sample, collect and name vertebrate helminths. While some have suggested that macroecology can work around existing data limitations, we argue that patterns described from a small, biased sample of diversity aren’t necessarily reliable, especially as host–parasite networks are increasingly altered by global change. In the spirit of moonshots like the Human Genome Project and the Global Virome Project, we consider the idea of a Global Parasite Project: a global effort to transform parasitology and inventory parasite diversity at an unprecedented pace.     

Contrasted histories of organelle and nuclear genomes underlying physiological diversification in a grass species

C₄ photosynthesis evolved multiple times independently in angiosperms, but most origins are relatively old so that the early events linked to photosynthetic diversification are blurred. The grass Alloteropsis semialata is an exception, as this species encompasses C₄ and non-C₄ populations. Using phylogenomics and population genomics, we infer the history of dispersal and secondary gene flow before, during and after photosynthetic divergence in A. semialata. We further analyse the genome composition of individuals with varied ploidy levels to establish the origins of polyploids in this species. Detailed organelle phylogenies indicate limited seed dispersal within the mountainous region of origin and the emergence of a C₄ lineage after dispersal to warmer areas of lower elevation. Nuclear genome analyses highlight repeated secondary gene flow. In particular, the nuclear genome associated with the C₄ phenotype was swept into a distantly related maternal lineage probably via unidirectional pollen flow. Multiple intraspecific allopolyploidy events mediated additional secondary genetic exchanges between photosynthetic types. Overall, our results show that limited dispersal and isolation allowed lineage divergence, with photosynthetic innovation happening after migration to new environments, and pollen-mediated gene flow led to the rapid spread of the derived C₄ physiology away from its region of origin.     

Species specificity and intraspecific variation in the chemical profiles of Heliconius butterflies across a large geographic range

In many animals, mate choice is important for the maintenance of reproductive isolation between species. Traits important for mate choice and behavioral isolation are predicted to be under strong stabilizing selection within species; however, such traits can also exhibit variation at the population level driven by neutral and adaptive evolutionary processes. Here, we describe patterns of divergence among androconial and genital chemical profiles at inter‐ and intraspecific levels in mimetic Heliconius butterflies. Most variation in chemical bouquets was found between species, but there were also quantitative differences at the population level. We found a strong correlation between interspecific chemical and genetic divergence, but this correlation varied in intraspecific comparisons. We identified “indicator” compounds characteristic of particular species that included compounds already known to elicit a behavioral response, suggesting an approach for identification of candidate compounds for future behavioral studies in novel systems. Overall, the strong signal of species identity suggests a role for these compounds in species recognition, but with additional potentially neutral variation at the population level.     

Best environmental predictors of breeding phenology differ with elevation in a common woodland bird species

Temperatures in mountain areas are increasing at a higher rate than the Northern Hemisphere land average, but how fauna may respond, in particular in terms of phenology, remains poorly understood. The aim of this study was to assess how elevation could modify the relationships between climate variability (air temperature and snow melt‐out date), the timing of plant phenology and egg‐laying date of the coal tit (Periparus ater). We collected 9 years (2011–2019) of data on egg‐laying date, spring air temperature, snow melt‐out date, and larch budburst date at two elevations (~1,300 m and ~1,900 m asl) on a slope located in the Mont‐Blanc Massif in the French Alps. We found that at low elevation, larch budburst date had a direct influence on egg‐laying date, while at high‐altitude snow melt‐out date was the limiting factor. At both elevations, air temperature had a similar effect on egg‐laying date, but was a poorer predictor than larch budburst or snowmelt date. Our results shed light on proximate drivers of breeding phenology responses to interannual climate variability in mountain areas and suggest that factors directly influencing species phenology vary at different elevations. Predicting the future responses of species in a climate change context will require testing the transferability of models and accounting for nonstationary relationships between environmental predictors and the timing of phenological events.