Host phenology regulates parasite–host demographic cycles and eco‐evolutionary feedbacks

Parasite–host interactions can drive periodic population dynamics when parasites overexploit host populations. The timing of host seasonal activity, or host phenology, determines the frequency and demographic impact of parasite–host interactions, which may govern whether parasites sufficiently overexploit hosts to drive population cycles. We describe a mathematical model of a monocyclic, obligate‐killer parasite system with seasonal host activity to investigate the consequences of host phenology on host–parasite dynamics. The results suggest that parasites can reach the densities necessary to destabilize host dynamics and drive cycling as they adapt, but only in some phenological scenarios such as environments with short seasons and synchronous host emergence. Furthermore, only parasite lineages that are sufficiently adapted to phenological scenarios with short seasons and synchronous host emergence can achieve the densities necessary to overexploit hosts and produce population cycles. Host‐parasite cycles also generate an eco‐evolutionary feedback that slows parasite adaptation to the phenological environment as rare advantageous phenotypes can be driven extinct due to a population bottleneck depending on when they are introduced in the cycle. The results demonstrate that seasonal environments can drive population cycling in a restricted set of phenological patterns and provide further evidence that the rate of adaptive evolution depends on underlying ecological dynamics.     

DNA diet profiles with high‐resolution animal tracking data reveal levels of prey selection relative to habitat choice in a crepuscular insectivorous bird

Given the global decline of many invertebrate food resources, it is fundamental to understand the dietary requirements of insectivores. We give new insights into the functional relationship between the spatial habitat use, food availability, and diet of a crepuscular aerial insectivore, the European Nightjar (Caprimulgus europaeus) by relating spatial use data with high‐throughput sequencing (HTS) combined with DNA metabarcoding. Our study supports the predictions that nightjars collect a substantial part of their daily nourishment from foraging locations, sometimes at considerable distance from nesting sites. Lepidopterans comprise 65% of nightjars'' food source. Nightjars tend to select larger species of Lepidoptera (>19 mm) which suggests that nightjars optimize the efficiency of foraging trips by selecting the most energetically favorable—larger—prey items. We anticipate that our findings may shed additional light on the interactions between invertebrate communities and higher trophic levels, which is required to understand the repercussions of changing food resources on individual‐ and population‐level processes.     

High‐throughput sequencing outperforms traditional morphological methods in Blue Catfish diet analysis and reveals novel insights into diet ecology

Blue Catfish Ictalurus furcatus are an invasive, yet economically important species in the Chesapeake Bay. However, their impact on the trophic ecology of this system is not well understood. In order to provide in‐depth analysis of predation by Blue Catfish, we identified prey items using high‐throughput DNA sequencing (HTS) of entire gastrointestinal tracts from 134 samples using two genetic markers, mitochondrial cytochrome c oxidase I (COI) and the nuclear 18S ribosomal RNA gene. We compared our HTS results to a more traditional “hybrid” approach that coupled morphological identification with DNA barcoding. The hybrid study was conducted on additional Blue Catfish samples (n = 617 stomachs) collected from the same location and season in the previous year. Taxonomic representation with HTS vastly surpassed that achieved with the hybrid methodology in Blue Catfish. Significantly, our HTS study identified several instances of at‐risk and invasive species consumption not identified using the hybrid method, supporting the hypothesis that previous studies using morphological methods may greatly underestimate consumption of critical species. Finally, we report the novel finding that Blue Catfish diet diversity inversely correlates to daily flow rates, perhaps due to higher mobility and prey‐seeking behaviors exhibited during lower flow.     

Temperature but not ocean acidification affects energy metabolism and enzyme activities in the blue mussel,Mytilus edulis

1. In mosaic marine habitats, such as intertidal zones, ocean acidification (OA) is exacerbated by high variability of pH, temperature, and biological CO₂ production. The nonlinear interactions among these drivers can be context‐specific and their effect on organisms in these habitats remains largely unknown, warranting further investigation.
2. We were particularly interested in Mytilus edulis (the blue mussel) from intertidal zones of the Gulf of Maine (GOM), USA, for this study. GOM is a hot spot of global climate change (average sea surface temperature (SST) increasing by >0.2°C/year) with >60% decline in mussel population over the past 40 years.
3. Here, we utilize bioenergetic underpinnings to identify limits of stress tolerance in M. edulis from GOM exposed to warming and OA. We have measured whole‐organism oxygen consumption rates and metabolic biomarkers in mussels exposed to control and elevated temperatures (10 vs. 15°C, respectively) and current and moderately elevated P _CO2 levels (~400 vs. 800 µatm, respectively).
4. Our study demonstrates that adult M. edulis from GOM are metabolically resilient to the moderate OA scenario but responsive to warming as seen in changes in metabolic rate, energy reserves (total lipids), metabolite profiles (glucose and osmolyte dimethyl amine), and enzyme activities (carbonic anhydrase and calcium ATPase).
5. Our results are in agreement with recent literature that OA scenarios for the next 100–300 years do not affect this species, possibly as a consequence of maintaining its in vivo acid‐base balance.

     

Multi‐omics of the expression and clinical outcomes of TMPRSS2 in human various cancers: A potential therapeutic target for COVID‐19

Growing evidence has shown that Transmembrane Serine Protease 2 (TMPRSS2) not only contributes to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, but is also closely associated with the incidence and progression of tumours. However, the correlation of coronavirus disease (COVID‐19) and cancers, and the prognostic value and molecular function of TMPRSS2 in various cancers have not been fully understood. In this study, the expression, genetic variations, correlated genes, immune infiltration and prognostic value of TMPRSS2 were analysed in many cancers using different bioinformatics platforms. The observed findings revealed that the expression of TMPRSS2 was considerably decreased in many tumour tissues. In the prognostic analysis, the expression of TMPRSS2 was considerably linked with the clinical consequences of the brain, blood, colorectal, breast, ovarian, lung and soft tissue cancer. In protein network analysis, we determined 27 proteins as protein partners of TMPRSS2, which can regulate the progression and prognosis of cancer mediated by TMPRSS2. Besides, a high level of TMPRSS2 was linked with immune cell infiltration in various cancers. Furthermore, according to the pathway analysis of differently expressed genes (DEGs) with TMPRSS2 in lung, breast, ovarian and colorectal cancer, 160 DEGs genes were found and were significantly enriched in respiratory system infection and tumour progression pathways. In conclusion, the findings of this study demonstrate that TMPRSS2 may be an effective biomarker and therapeutic target in various cancers in humans, and may also provide new directions for specific tumour patients to prevent SARS‐CoV‐2 infection during the COVID‐19 outbreak.     

Insulin binding to the analytical antibody sandwich pair OXI‐005 and HUI‐018: Epitope mapping and binding properties

The insulin epitopes for two monoclonal antibodies (mAbs), OXI‐005 and HUI‐018, commonly used in combination for insulin concentration determination in sandwich assays, were determined using X‐ray crystallography. The crystal structure of the HUI‐018 Fab in complex with human insulin (HI) was determined and OXI‐005 Fab crystal structures were determined in complex with HI and porcine insulin (PI) as well as on its own. The OXI‐005 epitope comprises insulin residues 1,3,4,19–21 (A‐chain) and 25–30 (B‐chain) and for HUI‐018 residues 7,8,10–14,17 (A‐chain) and 5–7, 10, 14 (B‐chain). The areas of insulin involved in interactions with the mAb are 20% (OXI‐005) and 24% (HUI‐018) of the total insulin surface. Based on the Fab complex crystal structures with the insulins a molecular model for simultaneous binding of the Fabs to PI was built and this model was validated by small angle X‐ray scattering measurements for the ternary complex. The epitopes for the mAbs on insulin were found well separated from each other as expected from luminiscent oxygen channeling immunoassay results for different insulins (HI, PI, bovine insulin, DesB30 HI, insulin glargine, insulin lispro). The affinities of the OXI‐005 and HUI‐018 Fabs for HI, PI, and DesB30 HI were determined using surface plasmon resonance. The K _Ds were found to be in the range of 1–4 nM for the HUI‐018 Fab, while more different for the OXI‐005 Fab (50 nM for HI, 20 nM for PI and 400 nM for DesB30 HI) supporting the importance of residue B30 for binding to OXI‐005.     

A genotyping‐in‐thousands by sequencing panel to inform invasive deer management using noninvasive fecal and hair samples

Studies in ecology, evolution, and conservation often rely on noninvasive samples, making it challenging to generate large amounts of high‐quality genetic data for many elusive and at‐risk species. We developed and optimized a Genotyping‐in‐Thousands by sequencing (GT‐seq) panel using noninvasive samples to inform the management of invasive Sitka black‐tailed deer (Odocoileus hemionus sitkensis) in Haida Gwaii (Canada). We validated our panel using paired high‐quality tissue and noninvasive fecal and hair samples to simultaneously distinguish individuals, identify sex, and reconstruct kinship among deer sampled across the archipelago, then provided a proof‐of‐concept application using field‐collected feces on SGang Gwaay, an island of high ecological and cultural value. Genotyping success across 244 loci was high (90.3%) and comparable to that of high‐quality tissue samples genotyped using restriction‐site associated DNA sequencing (92.4%), while genotyping discordance between paired high‐quality tissue and noninvasive samples was low (0.50%). The panel will be used to inform future invasive species operations in Haida Gwaii by providing individual and population information to inform management. More broadly, our GT‐seq workflow that includes quality control analyses for targeted SNP selection and a modified protocol may be of wider utility for other studies and systems where noninvasive genetic sampling is employed.     

Mitochondrial uncoupling protein‐2 reprograms metabolism to induce oxidative stress and myofibroblast senescence in age‐associated lung fibrosis

Mitochondrial dysfunction has been associated with age‐related diseases, including idiopathic pulmonary fibrosis (IPF). We provide evidence that implicates chronic elevation of the mitochondrial anion carrier protein, uncoupling protein‐2 (UCP2), in increased generation of reactive oxygen species, altered redox state and cellular bioenergetics, impaired fatty acid oxidation, and induction of myofibroblast senescence. This pro‐oxidant senescence reprogramming occurs in concert with conventional actions of UCP2 as an uncoupler of oxidative phosphorylation with dissipation of the mitochondrial membrane potential. UCP2 is highly expressed in human IPF lung myofibroblasts and in aged fibroblasts. In an aging murine model of lung fibrosis, the in vivo silencing of UCP2 induces fibrosis regression. These studies indicate a pro‐fibrotic function of UCP2 in chronic lung disease and support its therapeutic targeting in age‐related diseases associated with impaired tissue regeneration and organ fibrosis.     

Intermittent methionine restriction reduces IGF‐1 levels and produces similar healthspan benefits to continuous methionine restriction

A sustained state of methionine restriction (MR) dramatically extends the healthspan of several model organisms. For example, continuously methionine‐restricted rodents have less age‐related pathology and are up to 45% longer‐lived than controls. Promisingly, MR is feasible for humans, and studies have suggested that methionine‐restricted individuals may receive similar benefits to rodents. However, long‐term adherence to a methionine‐restricted diet is likely to be challenging for many individuals. Prompted by this, and the fact that intermittent variants of other healthspan‐extending interventions (i.e., intermittent fasting and the cyclic ketogenic diet) are just as effective, if not more, than their continuous counterparts, we hypothesized that an intermittent form of MR might produce similar healthspan benefits to continuous MR. Accordingly, we developed two increasingly stringent forms of intermittent MR (IMR) and assessed whether mice maintained on these diets demonstrate the beneficial metabolic changes typically observed for continuous MR. To the best of our knowledge, we show for the first time that IMR produces similar beneficial metabolic effects to continuous MR, including improved glucose homeostasis and protection against diet‐induced obesity and hepatosteatosis. In addition, like continuous MR, IMR confers beneficial changes in the plasma levels of the hormones IGF‐1, FGF‐21, leptin, and adiponectin. Together, our findings demonstrate that the more practicable intermittent form of MR produces similar healthspan benefits to continuous MR, and thus may represent a more appealing alternative to the classical intervention.     

High plasma concentrations of acyl‐coenzyme A binding protein (ACBP) predispose to cardiovascular disease: Evidence for a phylogenetically conserved proaging function of ACBP

Autophagy defects accelerate aging, while stimulation of autophagy decelerates aging. Acyl‐coenzyme A binding protein (ACBP), which is encoded by a diazepam‐binding inhibitor (DBI), acts as an extracellular feedback regulator of autophagy. As shown here, knockout of the gene coding for the yeast orthologue of ACBP/DBI (ACB1) improves chronological aging, and this effect is reversed by knockout of essential autophagy genes (ATG5, ATG7) but less so by knockout of an essential mitophagy gene (ATG32). In humans, ACBP/DBI levels independently correlate with body mass index (BMI) as well as with chronological age. In still‐healthy individuals, we find that high ACBP/DBI levels correlate with future cardiovascular events (such as heart surgery, myocardial infarction, and stroke), an association that is independent of BMI and chronological age, suggesting that ACBP/DBI is indeed a biomarker of “biological” aging. Concurringly, ACBP/DBI plasma concentrations correlate with established cardiovascular risk factors (fasting glucose levels, systolic blood pressure, total free cholesterol, triglycerides), but are inversely correlated with atheroprotective high‐density lipoprotein (HDL). In mice, neutralization of ACBP/DBI through a monoclonal antibody attenuates anthracycline‐induced cardiotoxicity, which is a model of accelerated heart aging. In conclusion, plasma elevation of ACBP/DBI constitutes a novel biomarker of chronological aging and facets of biological aging with a prognostic value in cardiovascular disease.     

Early‐life patterns of growth are linked to levels of phenotypic trait covariance and postfledging mortality across avian species

Life history studies have established that trade‐offs between growth and survival are common both within and among species. Identifying the factor(s) that mediate this trade‐off has proven difficult, however, especially at the among‐species level. In this study, we examined a series of potentially interrelated traits in a community of temperate‐zone passerine birds to help understand the putative causes and consequences of variation in early‐life growth among species. First, we examined whether nest predation risk (a proven driver of interspecific variation in growth and development rates) was correlated with species‐level patterns of incubation duration and nestling period length. We then assessed whether proxies for growth rate covaried with mean trait covariance strength (i.e., phenotypic correlations ( ^rp), which can be a marker of early‐life stress) among body mass, tarsus length, and wing length at fledging. Finally, we examined whether trait covariance strength at fledging was related to postfledging survival. We found that higher nest predation risk was correlated with faster skeletal growth and that our proxies for growth corresponded with increased trait covariance strength ( ^rp), which subsequently, correlated with higher mortality in the next life stage (postfledging period). These results provide an indication that extrinsic pressures (nest predation) impact rates of growth, and that there are costs of rapid growth across species, expressed as higher mean ^rp and elevated postfledging mortality. The link between higher levels of trait covariance at fledging and increased mortality is unclear, but increased trait covariance strength may reflect reduced phenotypic flexibility (i.e., phenotypic canalization), which may limit an organism''s capacity for coping with environmental or ecological variability.     

Permafrost response to temperature rise in carbon and nutrient cycling: Effects from habitat‐specific conditions and factors of warming

Permafrost is experiencing climate warming at a rate that is two times faster than the rest of the Earth''s surface. However, it is still lack of a quantitative basis for predicting the functional stability of permafrost ecosystems in carbon (C) and nutrient cycling. We compiled the data of 708 observations from 89 air‐warming experiments in the Northern Hemisphere and characterized the general effects of temperature increase on permafrost C exchange and balance, biomass production, microbial biomass, soil nutrients, and vegetation N dynamics through a meta‐analysis. Also, an investigation was made on how responses might change with habitat‐specific (e.g., plant functional groups and soil moisture status) conditions and warming variables (e.g., warming phases, levels, and timing). The net ecosystem C exchange (NEE) was found to be downregulated by warming as a result of a stronger sensitivity to warming in respiration (15.6%) than in photosynthesis (6.2%). Vegetation usually responded to warming by investing more C to the belowground, as belowground biomass increased much more (30.1%) than aboveground biomass (2.9%). Warming had a minor effect on microbial biomass. Warming increased soil ammonium and nitrate concentrations. What''s more, a synthesis of 70 observations from 11 herbs and 9 shrubs revealed a 2.5% decline of N in green leaves. Compared with herbs, shrubs had a stronger response to respiration and had a decline in green leaf N to a greater extent. Not only in dry condition did green leaf N decline with warming but also in wet conditions. Warming in nongrowing seasons would negatively affect soil water, C uptake, and biomass production during growing seasons. Permafrost C loss and vegetation N decline may increase with warming levels and timing. Overall, these findings suggest that besides a positive C cycling–climate feedback, there will be a negative feedback between permafrost nutrient cycling and climate warming.