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.
Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a ...poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease.
This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control.
Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio HR, 0.71 95% CI, 0.57 to 0.89;
= .003) and durvalumab + olaparib arms (HR, 0.55 95% CI, 0.43 to 0.69;
< .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR durvalumab
control, 0.42 95% CI, 0.22 to 0.80; HR durvalumab + olaparib
control, 0.41 95% CI, 0.21 to 0.75) and pMMR subgroups (HR durvalumab
control, 0.77 95% CI, 0.60 to 0.97; HR durvalumab + olaparib
control 0.57; 95% CI, 0.44 to 0.73); and in PD-L1-positive subgroups (HR durvalumab
control, 0.63 95% CI, 0.48 to 0.83; HR durvalumab + olaparib
control, 0.42 95% CI, 0.31 to 0.57). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab
control: HR, 0.77 95% CI, 0.56 to 1.07;
= .120; durvalumab + olaparib
control: HR, 0.59 95% CI, 0.42 to 0.83;
= .003). The safety profiles of the experimental arms were generally consistent with individual agents.
Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.
Modern neuromuscular electrodiagnosis (EDX) and neuromuscular ultrasound (NMUS) require a universal language for effective communication in clinical practice and research and, in particular, for ...teaching young colleagues. Therefore, the AANEM and the IFCN have decided to publish a joint glossary as they feel the need for an updated terminology to support educational activities in neuromuscular EDX and NMUS in all parts of the world. In addition NMUS has been rapidly progressing over the last years and is now widely used in the diagnosis of disorders of nerve and muscle in conjunction with EDX. This glossary has been developed by experts in the field of neuromuscular EDX and NMUS on behalf of the AANEM and the IFCN and has been agreed upon by electronic communication between January and November 2019. It is based on the glossaries of the AANEM from 2015 and of the IFCN from 1999. The EDX and NMUS terms and the explanatory illustrations have been updated and supplemented where necessary. The result is a comprehensive glossary of terms covering all fields of neuromuscular EDX and NMUS. It serves as a standard reference for clinical practice, education and research worldwide.
Highlights
Optimal terminology in neuromuscular electrodiagnosis and ultrasound has been revisited.
A team of international experts have revised and expanded a standardized glossary.
This list of terms serves as standard reference for clinical practice, education and research.
See editorial on page 1 in this issue.
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