Although climate change models predict relatively modest increases in temperature in the tropics by the end of the century, recent analyses identify tropical ectotherms as the organisms most at risk ...from climate warming. Because metabolic rate in ectotherms increases exponentially with temperature, even a small rise in temperature poses a physiological threat to tropical ectotherms inhabiting an already hot environment. If correct, the metabolic theory of climate warming has profound implications for global biodiversity, since tropical insects and arachnids constitute the vast majority of animal species. Predicting how climate change will translate into fitness consequences for tropical arthropods requires an understanding of the effects of temperature increase on the entire life history of the species. Here, in a comprehensive case study of the fitness consequences of the projected temperature increase for the tropics, we conducted a split‐brood experiment on the neotropical pseudoscorpion, Cordylochernes scorpioides, in which 792 offspring from 33 females were randomly assigned at birth to control‐ and high‐temperature treatments for rearing through the adult stage. The diurnally varying, control treatment temperature was determined from long‐term, average daily temperature minima and maxima in the pseudoscorpion's native habitat. In the high temperature treatment, increasing temperature by the 3.5 °C predicted for the tropics significantly reduced survival and accelerated development at the cost of reduced adult size and a dramatic decrease in level of sexual dimorphism. The most striking effects, however, involved reproductive traits. Reared at high temperature, males produced 45% as many sperm as control males, and females failed to reproduce. Sequencing of the mitochondrial ND2 gene revealed two highly divergent haplogroups that differed substantially in developmental rate and survivorship but not in reproductive response to high temperature. Our findings suggest that reproduction may be the Achilles’ heel of tropical ectotherms, as climate warming subjects them to an increasingly adverse thermal environment.
Maternal inheritance of mitochondria creates a sex‐specific selective sieve through which mitochondrial mutations harmful to males but not females accumulate and contribute to sexual differences in ...longevity and disease susceptibility. Because eggs and sperm are under disruptive selection, sperm are predicted to be particularly vulnerable to the genetic load generated by maternal inheritance, yet evidence for mitochondrial involvement in male fertility is limited and controversial. Here, we exploit the coexistence of two divergent mitochondrial haplogroups (A and B2) in a Neotropical arachnid to investigate the role of mitochondria in sperm competition. DNA profiling demonstrated that B2‐carrying males sired more than three times as many offspring in sperm competition experiments than A males, and this B2 competitive advantage cannot be explained by female mitochondrial haplogroup or male nuclear genetic background. RNA‐Seq of testicular tissues implicates differential expression of mitochondrial oxidative phosphorylation (OXPHOS) genes in the B2 competitive advantage, including a 22‐fold upregulation of atp8 in B2 males. Previous comparative genomic analyses have revealed functionally significant amino acid substitutions in differentially expressed genes, indicating that the mitochondrial haplogroups differ not only in expression but also in DNA sequence and protein functioning. However, mitochondrial haplogroup had no effect on sperm number or sperm viability, and, when females were mated to a single male, neither male haplogroup, female haplogroup nor the interaction between male/female haplogroup significantly affected female reproductive success. Our findings therefore suggest that mitochondrial effects on male reproduction may often go undetected in noncompetitive contexts and may prove more important in nature than is currently appreciated.
In central Panamanian populations of the harlequin beetle riding pseudoscorpion, Cordylochernes scorpioides, males carrying highly divergent mitochondrial haplogroups (A and B2) differ extensively in the expression of mtDNA genes in testicular tissue. DNA profiling demonstrates that B2‐carrying males sire more than three times as many offspring in two‐male sperm competition experiments than do A males, and this B2 competitive advantage cannot be explained by female mitochondrial haplogroup or male nuclear genetic background. Despite conferring strong fitness benefits on males, the B2 haplogroup remains rare in central Panamá as a consequence of male inability to transmit mitochondria to offspring (mother's curse).
Maternal inheritance of mitochondria creates a sex-specific selective sieve with implications for male longevity, disease susceptibility and infertility. Because males are an evolutionary dead end ...for mitochondria, mitochondrial mutations that are harmful or beneficial to males but not females cannot respond directly to selection. Although the importance of this male/female asymmetry in evolutionary response depends on the extent to which mitochondrial mutations exert antagonistic effects on male and female fitness, few studies have documented sex-specific selection acting on mitochondria. Here, we exploited the discovery of two highly divergent mitochondrial haplogroups (A and B2) in central Panamanian populations of the pseudoscorpion Cordylochernes scorpioides. Next-generation sequencing and phylogenetic analyses suggest that selection on the ND4 and ND4L mitochondrial genes may partially explain sexually antagonistic mitochondrial effects on reproduction. Males carrying the rare B2 mitochondrial haplogroup enjoy a marked advantage in sperm competition, but B2 females are significantly less sexually receptive at second mating than A females. This reduced propensity for polyandry is likely to significantly reduce female lifetime reproductive success, thereby limiting the spread of the male beneficial B2 haplogroup. Our findings suggest that maternal inheritance of mitochondria and sexually antagonistic selection can constrain male adaptation and sexual selection in nature.
Recent theory suggests that global warming may be catastrophic for tropical ectotherms. Although most studies addressing temperature effects in ectotherms utilize constant temperatures, Jensen's ...inequality and thermal stress considerations predict that this approach will underestimate warming effects on species experiencing daily temperature fluctuations in nature. Here, we tested this prediction in a neotropical pseudoscorpion. Nymphs were reared in control and high-temperature treatments under a constant daily temperature regime, and results compared to a companion fluctuating-temperature study. At constant temperature, pseudoscorpions outperformed their fluctuating-temperature counterparts. Individuals were larger, developed faster, and males produced more sperm, and females more embryos. The greatest impact of temperature regime involved short-term, adult exposure, with constant temperature mitigating high-temperature effects on reproductive traits. Our findings demonstrate the importance of realistic temperature regimes in climate warming studies, and suggest that exploitation of microhabitats that dampen temperature oscillations may be critical in avoiding extinction as tropical climates warm.
Recent theory suggests that tropical terrestrial arthropods are at significant risk from climate warming. Metabolic rate in such ectothermic species increases exponentially with environmental ...temperature, and a small temperature increase in a hot environment can therefore have a greater physiological impact than a large temperature increase in a cool environment. In two recent studies of the neotropical pseudoscorpion,
, simulated climate warming significantly decreased survival, body size and level of sexual dimorphism. However, these effects were minor compared with catastrophic consequences for male fertility and female fecundity, identifying reproduction as the life stage most vulnerable to climate warming. Here, we examine the effects of chronic high-temperature exposure on epigenetic regulation in
in the context of naturally occurring variation in mitochondrial DNA. Epigenetic mechanisms, including DNA methylation, histone modifications and small non-coding RNA (sncRNA) expression, are particularly sensitive to environmental factors such as temperature, which can induce changes in epigenetic states and phenotypes that may be heritable across generations. Our results indicate that exposure of male pseudoscorpions to elevated temperature significantly altered the expression of >60 sncRNAs in testicular tissue, specifically microRNAs and piwi-interacting RNAs. Mitochondrial haplogroup was also a significant factor influencing both sncRNAs and mitochondrial gene expression. These findings demonstrate that chronic heat stress causes changes in epigenetic profiles that may account for reproductive dysfunction in
males. Moreover, through its effects on epigenetic regulation, mitochondrial DNA polymorphism may provide the potential for an adaptive evolutionary response to climate warming.
Fractional and fractal derivatives are both generalizations of the usual derivatives that consider derivatives of non-integer orders. Interest in these generalizations has been triggered by a ...resurgence of clamor to develop a mathematical tool to describe “roughness” in the spirit of Mandelbrot’s (1967) fractal geometry. Fractional derivatives take the analytic approach towards developing a rational order derivative while fractal derivatives follow a more concrete, albeit geometric approach to the same end. Since both approaches alleged to extend whole derivatives to rational derivatives, it is not surprising that confusion will arise over which generalization to use in practice. This paper attempts to highlight the connection between the various generalizations to fractional and fractal derivatives with the end-in-view of making these concepts useful in various physics applications and to resolve some of the confusion that arise out of the fundamental philosophical differences in the derivation of fractional derivatives (non-local concept) and fractal derivatives (local concept).
Maternal inheritance of mitochondria creates a sex-specific selective sieve with implications for male longevity, disease susceptibility and infertility. Because males are an evolutionary dead end ...for mitochondria, mitochondrial mutations that are harmful or beneficial to males but not females cannot respond directly to selection. Although the importance of this male/female asymmetry in evolutionary response depends on the extent to which mitochondrial mutations exert antagonistic effects on male and female fitness, few studies have documented sex-specific selection acting on mitochondria. Here, we exploited the discovery of two highly divergent mitochondrial haplogroups (A and B2) in central Panamanian populations of the pseudoscorpion Cordylochemes scorpioides. Next-generation sequencing and phylogenetic analyses suggest that selection on the ND4 and ND4L mitochondrial genes may partially explain sexually antagonistic mitochondrial effects on reproduction. Males carrying the rare B2 mitochondrial haplogroup enjoy a marked advantage in sperm competition, but B2 females are significantly less sexually receptive at second mating than A females. This reduced propensity for polyandry is likely to significantly reduce female lifetime reproductive success, thereby limiting the spread of the male beneficial B2 haplogroup. Our findings suggest that maternal inheritance of mitochondria and sexually antagonistic selection can constrain male adaptation and sexual selection in nature.
Females produce few, large and costly eggs, whereas males produce many small and physiologically inexpensive sperm. This differential investment in gametes has long been identified as a force driving ...the evolution of divergent mating tactics in the sexes. In most species, anisogamy is also coupled with strict maternal inheritance of genetic elements in the cytoplasm, including DNA in cellular endosymbionts and mitochondria. Because males are an evolutionary dead end for mitochondria, mutations in the mitochondrial genome that are harmful or beneficial to males but not to females cannot respond directly to selection. Few studies have documented sex-specific selection acting on mitochondria, and its general evolutionary significance remains poorly understood. As a polyandrous, viviparous invertebrate with indirect sperm transfer, the pseudoscorpion, Cordylochernes scorpioides, possesses a suite of reproductive and behavioral traits that makes it ideally suited for investigating the effects of mtDNA variation on male adaptation and sexual selection. Mitochondrial genome sequencing and phylogenetic analyses have revealed the coexistence of two highly divergent mitochondrial haplogroups, Clades A and B2, in central Panamá. DNA profiling demonstrated that B2-haplogroup males enjoyed a significant sperm competitive advantage, siring 2.5 times as many offspring as A- haplogroup males in two-male sperm competition experiments. However, mtDNA variation also influenced female sexual receptivity on second mating, with B2-haplogroup females significantly less likely to accept sperm from a second male. Taken together, these findings suggest that, despite its highly advantageous effects on sperm competitive ability, the B2 haplogroup is constrained to low frequency in central Panamanian populations of C. scorpioidesbecause of its negative consequences for females, in terms of reduced propensity for adaptive polyandrous behavior among females carrying B2 haplogroup mitochondria.
5595 Background: DUO-E (NCT04269200) showed statistically significant, clinically meaningful improvement in progression-free survival (PFS) with addition of durvalumab to CP, followed by durvalumab ± ...the PARP inhibitor olaparib, vs CP alone for patients (pts) with EC (Westin SN et al. J Clin Oncol 2024;42:283–99). PARP inhibitors are an established approach to targeting tumors with homologous recombination deficiency, so we performed post hoc exploratory analyses of PFS by BRCAm status. Methods: Pts with newly diagnosed FIGO Stage III/IV or recurrent EC and naïve to first-line systemic treatment were randomized 1:1:1 to CP (CP + durvalumab placebo pbo; 6 cycles followed by durvalumab pbo + olaparib pbo), CP+D (CP + durvalumab 1120 mg q3w; 6 cycles followed by durvalumab 1500 mg q4w + olaparib pbo) or CP+D+O (CP + durvalumab 6 cycles followed by durvalumab + olaparib 300 mg bid). Tissue BRCAm status was determined retrospectively (FoundationOneCDx assay, Foundation Medicine). Results: Of 718 pts randomized, 19.9% were mismatch repair deficient (dMMR) and 80.1% MMR proficient (pMMR). At primary analysis (April 12, 2023), PFS improvement was observed for CP+D and CP+D+O vs CP irrespective of BRCAm status (Table). BRCAm prevalence was low overall (dMMR: 12.6% BRCAm, 61.5% non-BRCAm, 25.9% unknown; pMMR: 4.0% BRCAm, 65.9% non-BRCAm, 30.1% unknown). PFS outcomes for CP+D+O vs CP in pMMR non-BRCAm pts (HR 0.57, 95% CI 0.42–0.78) were consistent with the overall pMMR subgroup (HR 0.57, 95% CI 0.44–0.73); BRCAm subgroup analyses were descriptive due to small sample size. Conclusions: Clinical benefit with addition of durvalumab to CP, followed by durvalumab + olaparib, vs CP alone was observed in the ITT and pMMR populations irrespective of BRCAm status. Clinical trial information: NCT04269200 . Table: see text
5599 Background: DUO-E (NCT04269200) showed statistically significant and clinically meaningful progression-free survival improvement with addition of durvalumab (D) to carboplatin/paclitaxel (CP) ...followed by D ± olaparib (O) vs CP alone for patients (pts) with EC (Westin SN et al. J Clin Oncol 2024;42:283–99). We describe safety and tolerability, focusing on the most common adverse events (AEs). Methods: Pts with newly diagnosed FIGO Stage III/IV or recurrent EC and naïve to systemic treatment were randomized 1:1:1 to CP (CP + D placebo pbo; 6 cycles followed by D pbo + O pbo), CP+D (CP + D 1120 mg IV q3w; 6 cycles followed by D 1500 mg IV q4w + O pbo), or CP+D+O (CP + D 6 cycles followed by D + O 300 mg tablets bid). Safety was assessed through AEs. Results: 709 pts (19.3% mismatch repair deficient dMMR, 80.7% MMR proficient pMMR) received treatment (CP: n=236; CP+D: n=235; CP+D+O: n=238). Total median treatment duration with D/pbo was 9.0, 9.9 and 13.1 months in the CP, CP+D and CP+D+O arms and 5.7, 7.6 and 9.2 months withO/pbo, respectively. 18.6%, 20.9% and 24.4% of pts in the CP, CP+D and CP+D+O arm, respectively, had AEs leading to treatment discontinuations, 50.0%, 54.5% and 68.9% had AEs leading to dose interruptions, and 56.4%, 54.9% and 67.2% had grade ≥3 AEs. There was no increase in immune-mediated AEs or AEs of special interest for O with CP+D+O. There were 3 cases of pure red-cell aplasia with CP+D+O (all grade 3) and 3 of autoimmune hemolytic anemia (1 with CP+D, 2 with CP+D+O; all grade 3). The most common AEs were mostly low grade, with grade 3/4 in few pts (anemia 14%, 16%, 24% in the CP, CP+D, CP+D+O arms, respectively, alopecia 0%, 0%, 0%, nausea 1%, <1%, 3%, fatigue 2%, 2%, 2%), and led to few treatment discontinuations and interruptions (Table). AE profiles were generally consistent across MMR subgroups. Conclusions: In DUO-E, safety findings were generally consistent with the known safety profiles of CP, D and O. The addition of D to CP followed by D or by D + O resulted in expected and manageable safety profiles compared with CP alone, with the most common AEs being low grade and leading to few discontinuations or dose modifications/interruptions of D/pbo or O/pbo. Clinical trial information: NCT04269200 . Table: see text
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