Biology subjects

Piper, M.

Publications and source records attributed to Piper, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Single-nucleus multi-omics reveals reversible molecular signatures in skeletal muscle of patients with heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a complex systemic syndrome characterized by severe exercise intolerance. In addition to cardiac dysfunction, abnormalities in peripheral skeletal muscle are key contributors to reduced exercise capacity in HFpEF. Multiple studies show that exercise training and caloric restriction improve exercise capacity and quality of life in HFpEF patients. To map the HFpEF-associated molecular signatures in skeletal muscle and the effect of lifestyle intervention, we generated single-nucleus (sn) multiome (joint snRNA-seq and snATAC-seq) profiles of 140 biopsies. Our study included 95 individuals: 25 healthy controls and 70 HFpEF patients, of whom 45 had paired biopsies collected before and after a supervised diet and exercise intervention. From 132,568 nuclei, we resolved 15 skeletal muscle cell types and identified HFpEF-specific remodeling, including type 1 fiber and pericyte depletion and type 2x fiber enrichment, reflecting the cellular basis of exercise intolerance. Transcriptional changes in HFpEF muscle indicated dysregulation of metabolic pathways, stress-responsive programs, cytoskeletal integrity, and calcium signaling. Transcription factor (TF) motifs enriched in differentially accessible chromatin corresponded to concordantly differentially expressed TF-genes, revealing coordinated regulatory programs underlying these changes. Importantly, HFpEF-related changes in both chromatin accessibility and transcription were partially reversible following diet and exercise. Integrative multiomic velocity analyses revealed increased coordinated repression in both chromatin accessibility and transcription of calcium handling genes in HFpEF. HFpEF-linked chromatin was enriched for HF and cardiometabolic GWAS signals, and cross-modal analyses further nominated candidate causal variants and effector genes linking genetic risk to peripheral muscle dysfunction in HFpEF. Together, these findings highlight the molecular mechanisms underlying skeletal muscle remodeling in HFpEF and identify pathways responsive to lifestyle interventions.

genomics↗

bioRxiv2026

Systematic Regional Bias is Widespread in ChIP-seq

Robust and reproducible results are essential for confident scientific analysis. We demonstrate that transcription factor (TF) Chromatin Immunoprecipitation coupled with sequencing (ChIP-seq) suffers from systematic bias that may threaten its reproducibility: 80% of 200+ condition-matched, dual-replicate experiments in ENCODE contain genomic regions of systematic bias. We observe this regional bias even between replicates produced within the same experiment, resulting in thousands of unreplicated peaks, which often contain valuable biological data. We provide evidence that regional bias may lead to qualitative differences in TF biology inferred by different experiments; we discovered eight TFs with binding activity in compact chromatin that was identified by one experiment, yet systematically absent from others. To mitigate the effects of bias, we derive simple but effective metrics to quantify the quality of data within biased regions and demonstrate that they can be used for the robust integration of data from multiple experiments.

bioinformatics↗

bioRxiv2026

Genetic demultiplexing and transcript start site identification from nanopore sequencing of 10x Genomics multiome libraries

Short-read Illumina sequencing of 10x Genomics single-nucleus multiome libraries captures only the 3 end of RNA transcripts, losing transcription start site (TSS) information. Here we demonstrate nanopore sequencing of 10x multiome libraries, which enables the profiling of full length transcripts. We show concordance with common short-read sequencing based workflows including successful genetic demultiplexing of nanopore data despite its higher error rate. We compare TSS identified using nanopore sequencing of multiome cDNA to those identified using a short-read 5 assay, and provide an optimized approach for the preprocessing of nanopore reads prior to TSS identification. We find that nanopore sequencing of multiome cDNA captures a median of 63% of the TSS detected by the 5 assay.

bioinformatics↗

bioRxiv2026

Vgll2 and Tead1 Govern Generation of Mouse and Human Hypothalamic Hypocretin (Orexin) Neurons

The hypothalamic hypocretin (Hcrt; aka orexin) neuropeptide neurons are crucial for wakefulness and their malfunction results in narcolepsy; a devastating disorder without current cures. Transplantation of mouse Hcrt cells into mouse narcolepsy models is pointing to cell therapy as a potential treatment for narcolepsy. However, progress in this area requires decoding the developmental pathways generating human HCRT neurons and a deeper understanding of their diversity and physiology. Here, we identify the hypothalamic progenitor domain generating mouse Hcrt neurons and propose a conserved mouse/human genetic cascade driving Hcrt specification. This cascade involves the Vgll2 and Tead1 transcription factor partners, which we find are crucial for mouse Hcrt neuron generation. Conversely, co-misexpression of VGLL2 and TEAD1 in human stem cell derived hypothalamic organoids can induce HCRT neuron differentiation. These findings provide an important element for the development of human induced HCRT neurons for physiological studies and for cell therapy in narcolepsy.

neuroscience↗

bioRxiv2026

Phenotypic reversion and target prioritization for cellular inflammation via representation learning with foundation models

The identification of genetic perturbations that can reverse disease-associated cellular phenotypes toward a healthy state is a central challenge in early drug discovery. We present a proof-of-concept framework leveraging single-cell foundation models (scFMs) and a large-scale Perturb-seq dataset to prioritize targets for phenotypic reversion of cellular inflammation. We incorporated both basal and proinflammatory signaling conditions, specifically stimulation with interleukin-1 beta (IL-1{beta}) and tumor necrosis factor alpha (TNF-), to assess whether atherosclerotic disease-relevant stimulation improved identification of genes and pathways critical to disease progression. Our dataset comprised 864,115 endothelial cells subjected to 1,740 unique genetic perturbations. Through having both conditions, we identified targets that exhibited differential effects on gene expression dependent on cellular state. Using scFMs, we embedded single-cell transcriptomes into high-dimensional latent spaces and ranked perturbations by their ability to shift the inflammatory transcriptomic profile toward that of untreated controls. Benchmarking against both annotated gene sets and expert-curated targets, we found robust enrichment for known regulators of inflammation and biologically relevant targets, despite these models having no prior information about these targets. Importantly, including both basal and proinflammatory conditions improved identification of inflammation-associated targets compared to using just the basal condition. This underscored the value of incorporating disease-relevant stimulations in perturbation experiments. Our results highlight the utility of scFMs for data-driven target nomination, emphasize the role of cellular state in regulatory responses, and provide a scalable, model-agnostic approach for ML-guided target discovery. This work offers a valuable community resource for advancing biological understanding of inflammatory-associated disease.

bioinformatics↗

bioRxiv2025

CD300LG is a receptor for triglyceride-rich lipoproteins that facilitates postprandial lipid clearance

Circulating triglycerides are principally transported by triglyceride-rich lipoprotein particles (TRLs) including very-low-density-lipoproteins (VLDL) and chylomicrons and require the activity of lipoprotein lipase for appropriate lipid processing and cellular uptake. Despite known genetic links between CD300LG variants and altered lipid profiles, the functional role of CD300LG in lipid metabolism remains unclear. In this study, we identify CD300LG as a crucial receptor for TRLs. Human genetic analyses reveal that reduced CD300LG protein levels are causally linked with CAD risk and increased number, diameter, and TAG concentration of TRLs. In mice, CD300LG deficiency results in postprandial hypertriglyceridemia independent of changes in VLDL secretion, intestinal lipid absorption, or lipoprotein lipase activity. Mechanistically, CD300LG acts as a receptor for TRLs through a direct interaction with ApoA4 to facilitate TRL clearance at the microvascular endothelium. These findings elucidate new functions for both CD300LG and ApoA4 and advance our general understanding of triglyceride metabolism.

physiology↗

bioRxiv2025

Dietary Zn governs protein: carbohydrate regulation of fecundity and lifespan in Drosophila melanogaster

Recent work has shown that dietary zinc (Zn) restriction has a strong effect to limit egg production in female Drosophila, while also producing a variable, but beneficial, effect on lifespan. This combination of phenotypes is interesting because it is consistent with the disposable soma theory of ageing, and phenocopies the well-studied effects of reducing the dietary protein-to-carbohydrate (P:C) ratio. Thus, Zn restriction may be a key precision nutrition intervention to extend lifespan. To investigate this, we decided to assess the interactive effects of dietary Zn and P:C ratios on reproduction and lifespan. We found that the interventions interact, producing equally strong, but not additive, effects to modify female reproduction and lifespan. Specifically, both Zn restriction and lowering the P:C ratio reduced reproduction and benefited lifespan, but only when the other nutrient was maintained at high levels. When either Zn or P:C was at intermediate or low levels, adjusting the other nutritional component varied reproduction, but did so independently of lifespan, which remained fixed at a high level. Disrupting the Zn transporter, white, modified the magnitude of some effects, but not their direction. Thus, the micronutrient Zn modifies life-history outcomes to the same extent as altering the macronutrient (P:C) ratio, indicating its nutritional availability is likely to be a key determinant of fitness for Drosophila.

evolutionary biology↗

bioRxiv2024

Sox9 and Nfi transcription factors regulate the timing of neurogenesis and ependymal maturation in dopamine progenitors

Correct timing of neurogenesis is critical for both generating the correct number and subtypes of glia and neurons in the embryo, as well as preventing tumours and the depletion of stem cell pools in the adults. Here we analyse how the midbrain dopamine neuron (mDA) progenitors transition into cell cycle arrest (G0) and begin to mature into ependymal cells. The comparison of mDA progenitors from different embryonic stages revealed the upregulation of Nfi and Sox9 transcription factors during development. Their conditional inactivation in the early embryonic midbrain leads to delayed G0 entry and ependymal maturation, reduced gliogenesis, and increased generation of neurons, including mDA neurons. In contrast, their inactivation in late embryogenesis does not result in mitotic re-entry, suggesting that these factors are necessary for the G0 induction, but not for its maintenance. Our characterisation of mDA-progenitor-derived adult ependymal cells by single-cell RNA sequencing and histology show that they both retain several progenitor features but also secrete neuropeptides and contact neighbouring cells and blood vessels, indicating that these cells may form a novel part of the circumventricular organ system.

developmental biology↗

bioRxiv2024

IL15/IL15Rα complex induces an anti-tumor immune response following radiation therapy only in the absence of Tregs and fails to induce expansion of progenitor TCF1+ CD8 T cells

BackgroundThis work seeks to understand whether IL15-incorporating treatments improve response to radiotherapy and uncover mechanistic rationale for overcoming resistance to IL15 agonism using novel therapeutic combinations. Experimental DesignOrthotopic tumor models of PDAC were used to determine response to treatment. IL15-/- and Rag1-/- mouse models were employed to determine dependence on IL15 and CTLs, respectively. Flow cytometry was used to assess immune cell frequency and activation state. Phospho-proteomic analyses were used to characterize intracellular signaling pathways. ResultsWe show that the combination of radiation therapy (RT) and an IL15/IL15Ra fusion complex (denoted IL15c) fails to confer anti-tumor efficacy; however, a CD8-driven anti-tumor immune response is elicited with the concurrent administration of an aCD25 Treg-depleting antibody. Using IL15-/- and Rag1-/- mice, we demonstrate that response to RT + IL15c + aCD25 is dependent on both IL15 and CTLs. Furthermore, despite an equivalent survival benefit following treatment with RT + IL15c + aCD25 and combination RT + PD1-IL2v, a novel immunocytokine with PD-1 and IL2R{beta}{gamma} binding domains, CTL immunophenotyping and phospho-proteomic analysis of intracellular metabolites showed significant upregulation of activation and functionality in CD8 T cells treated with RT + PD1-IL2v. Finally, we show the immunostimulatory response to RT + PD1-IL2v is significantly diminished with a concurrent lack of TCF+ CD8 T cell generation in the absence of functional IL15 signaling. ConclusionsOur results are illustrative of a mechanism wherein unimpeded effector T cell activation through IL2R{beta} signaling and Treg inhibition are necessary in mediating an anti-tumor immune response.

cancer biology↗

bioRxiv2024

Divergent response to radio-immunotherapy is defined by intrinsic features of the tumor microenvironment

BackgroundTreatment with immunotherapy can elicit varying responses across cancer types, and the mechanistic underpinnings that contribute to response vs. progression remain poorly understood. However, to date there are few preclinical models that accurately represent these disparate disease scenarios. MethodsUsing combinatorial radio-immunotherapy consisting of PD-1 blockade, IL2R{beta}{gamma} biased signaling, and OX40 agonism we were able to generate preclinical tumor models with conflicting responses, where head and neck squamous cell carcinoma (HNSCC) models responds and pancreatic ductal adenocarcinoma (PDAC) progresses. ResultsBy modeling these disparate states, we find that regulatory T cells (Tregs) are expanded in PDAC tumors undergoing treatment, constraining tumor reactive CD8 T cell activity. Consequently, the depletion of Tregs restores the therapeutic efficacy of our treatment and abrogates the disparity between models. Moreover, we show that through heterotopic implantations that the site of tumor development defines the response to therapy, as implantation of HNSCC tumors into the pancreas resulted in comparable levels of tumor progression. ConclusionsThis work highlights complexity of combining immunotherapies within the tumor microenvironment and further defines the immune and non-immune components of the tumor microenvironment as an intrinsic feature of immune suppression. What is already known on this topicO_LIIn Head and neck squamous cell carcinomas (HNSCC) and pancreatic ductal adenocarcinoma (PDAC), targeting PD-1 and IL2R{beta}{gamma} simultaneously (PD1-IL2v) has been shown to be effective when combined with radiation therapy (RT), yet complete response is still limited. The T cell co-stimulatory receptor OX40 (TNFRSF4) has pleiotropic effects, promoting T cell survival, expansion, and memory differentiation in conventional effector T cells, while subsequently limiting regulatory T cell (Treg) suppression by constraining induction and expression of Foxp3. Expression of OX40 is highly upregulated after treatment with PD1-IL2v, and we postulated that combining OX40 agonism with PD1-IL2v and RT would provide additional benefit. C_LI What this study addsO_LIUsing orthotopic models of HNSCC and PDAC, we found that the addition of OX40 agonism unexpectedly drives tumor progression in PDAC, but not HNSCC. Intriguingly, this effect dependent on the tumor microenvironment as the effect is reversed by swapping the location of tumor implantation. This progression was also abrogated by the depletion of regulatory T cells (Tregs), a known mediator of resistance in these models. C_LI How this study might affect research, practice or policyO_LIOur data demonstrate that unexpected and deleterious effects can stem from combining multiple immunotherapies. These findings hold particular translational relevance as the use of combination immunotherapies is increasingly common on trial. C_LI

immunology↗

bioRxiv2023

Integrated omics analysis unveils a DNA damage response to neurogenic injury

Spinal cord injury (SCI) evokes profound bladder dysfunction. Current treatments are limited by a lack of molecular data to inform novel therapeutic avenues. Previously, we showed systemic inosine treatment improved bladder function following SCI in rats. Here, we applied multi-omics analysis to explore molecular alterations in the bladder and their sensitivity to inosine following SCI. Canonical pathways regulated by SCI included those associated with protein synthesis, neuroplasticity, wound healing, and neurotransmitter degradation. Upstream regulator analysis identified MYC as a key regulator, whereas causal network analysis predicted multiple regulators of DNA damage response signaling following injury, including PARP-1. Staining for both DNA damage ({gamma}H2AX) and PARP activity (poly-ADP-ribose) markers in the bladder was increased following SCI, and attenuated in inosine-treated tissues. Proteomics analysis suggested that SCI induced changes in protein synthesis-, neuroplasticity-, and oxidative stress-associated pathways, a subset of which were shown in transcriptomics data to be inosine-sensitive. These findings provide novel insights into the molecular landscape of the bladder following SCI, and highlight a potential role for PARP inhibition to treat neurogenic bladder dysfunction. Synopsis O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/571015v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@7c3e79org.highwire.dtl.DTLVardef@e998f5org.highwire.dtl.DTLVardef@38fd4aorg.highwire.dtl.DTLVardef@17d3aba_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIEmployed a multi-omics approach, integrating both transcriptomic and proteomic analyses, to investigate the molecular response in a rat model of spinal cord injury (SCI) and the therapeutic effect of inosine. C_LIO_LIDiscovered multiple regulators of the DNA damage response, including PARP-1, using causal network analysis. C_LIO_LIObserved decreased markers of DNA damage and PARP activity in inosine-treated tissues, indicating the therapeutic potential of inosine in neurogenic dysfunction. C_LIO_LIIdentified significant alterations in molecular pathways associated with protein synthesis, neuroplasticity, wound healing, and neurotransmitter degradation after SCI, and their modulation by inosine, highlighting its neuroprotective effects beyond DNA damage repair. C_LI

cell biology↗

bioRxiv2023

Polycomb Repressive Complex 2 is critical for mouse cortical glutamatergic neuron development

The Polycomb Repressive Complex 2 (PRC2) regulates corticogenesis, yet the consequences of mutations to this epigenetic modifier in the mature brain are poorly defined. Importantly, PRC2 core genes are haploinsufficient and causative for several human neurodevelopmental disorders. To address the role of PRC2 in mature cortical structure and function, we conditionally mutated the PRC2 gene Eed in the developing mouse telencephalon. Adult homozygotes displayed smaller forebrain structures. Single-nucleus transcriptomics revealed glutamatergic neurons were particularly affected, exhibiting dysregulation of cortical layer-specific profiles, accompanied by aberrations in neuronal morphology and connectivity. Incredibly, homozygous mice performed well on challenging cognitive tasks. In contrast, heterozygous mice did not exhibit anatomical or behavioral phenotypes but displayed dysregulation of neuronal genes and altered neuronal morphology that was strikingly different from homozygous phenotypes. Collectively, we demonstrate how alterations to PRC2 function shape the mature brain and reveal a dose-specific role for PRC2 in determining glutamatergic neuron identity.

developmental biology↗

bioRxiv2023

SPAG7 deletion causes intrauterine growth restriction, resulting in adulthood obesity and metabolic dysfunction

From a forward mutagenetic screen to discover mutations associated with obesity, we identified mutations in the spag7 gene linked to metabolic dysfunction in mice. Here we show that SPAG7 KO mice are born smaller and develop obesity and glucose intolerance in adulthood. This obesity does not stem from hyperphagia, but a decrease in energy expenditure. The KO animals also display reduced exercise tolerance and muscle function due to impaired mitochondrial function. Furthermore, SPAG7-deficiency in developing embryos leads to intrauterine growth restriction, brought on by placental insufficiency, likely due to abnormal development of the placental junctional zone. This insufficiency leads to loss of SPAG7-deficient fetuses in utero and reduced birth weights of those that survive. We hypothesize that a "thrifty phenotype" is ingrained in SPAG7 KO animals during development that leads to adult obesity. Collectively, these results indicate that SPAG7 is essential for embryonic development and energy homeostasis later in life.

molecular biology↗

bioRxiv2022

Sex-specific transgenerational effects of diet on offspring life history and physiology

Dietary variation in males and females can shape the expression of offspring life histories and physiology. However, the relative contributions of maternal and paternal dietary variation to phenotypic expression of latter generations is currently unknown. We provided male and female Drosophila melanogaster diets differing in sucrose concentration prior to reproduction, and similarly subjected grandoffspring to the same treatments. We then investigated the phenotypic consequences of this dietary variation among grandsons and granddaughters. We demonstrate transgenerational effects of dietary sucrose, mediated through the grandmaternal lineage, which mimic the direct effects of sucrose on lifespan, with opposing patterns across sexes; low sucrose increased female, but decreased male, lifespan. Dietary mismatching of grandoffspring-grandparent diets increased lifespan and reproductive success, and moderated triglyceride levels, of grandoffspring, providing insights into the physiological underpinnings of the complex transgenerational effects on life histories.

evolutionary biology↗

bioRxiv2022

Targeting OLIG2 increases therapeutic responses in SHH medulloblastoma mouse models and patient-derived medulloblastoma organoids

Recurrence after therapy is the primary life-threatening complication of medulloblastoma. In Sonic Hedgehog (SHH)-subgroup medulloblastoma, OLIG2-expressing tumour stem cells are crucial to recurrence. We investigated the potential of the small-molecule OLIG2 inhibitor CT-179 to decrease recurrence in patient-derived organoids, mice genetically-engineered to develop SHH-driven MB, and mice with MB patient-derived xenograft (PDX) tumours. We found that OLIG2 mRNA significantly correlated with poor survival in patients with SHH-MB, but not other subgroups. CT-179 rapidly downregulated OLIG2 protein in vitro and displayed nanomolar IC50 values. CT-179 arrested MB cells at G2/M, with degradation of cyclin B1 and phospho-CDK1 inducing apoptosis. In vivo CT-179 induced similar cell cycle changes in MBs in Smo-mutant mice and significantly increased mouse survival. In both MB organoids and mouse models, CT-179 combined with radiotherapy showed greater efficacy than either treatment alone. These data highlight the potential for OLIG2-targeted therapy to improve MB outcomes by targeting recurrent disease.

cancer biology↗

bioRxiv2021

The Biosynthetic Costs of Amino Acids at the Base of the Food Chain Determine Their Use in Higher-order Consumer Genomes

Dietary nutrient composition is essential for shaping important fitness traits and behaviours. Many organisms are protein limited and for Drosophila melanogaster, this limitation manifests at the level of the single most limiting essential Amino Acid (AA) in the diet. The identity of this AA and its effects on female fecundity is readily predictable by a procedure called exome matching in which the sum of AAs encoded by a consumers exome is used to predict the relative proportion of AAs required in its diet. However, the exome matching calculation does not weight AA contributions to the overall profile by protein size or expression. Here we update the exome matching calculation to include these weightings. Surprisingly, although nearly half of the transcriptome is differentially expressed when comparing male and female flies, we found that creating transcriptome-weighted exome matched diets for each sex did not enhance their fecundity over that supported by exome matching alone. These data indicate that while organisms may require different amounts of dietary protein across conditions, the relative proportion of the constituent AAs remains constant. Interestingly, we also found remarkable conservation of exome matched AA profiles across taxa and that the composition of these profiles could be explained by the metabolic costs of microbial AA synthesis. Thus, it appears that bioenergetic constraints amongst autotrophs shape the relative proportion of AAs that are available across trophic levels and that that this constrains biomass composition.

genomics↗

bioRxiv2021

Restricting a single amino acid cross-protects D. melanogaster from nicotine poisoning through mTORC1 and GCN2 signalling.

Dietary interventions that restrict protein intake have repeatedly been shown to offer beneficial health outcomes to the consumer. Benefits such as increased stress tolerance can be observed in response to restricting individual amino acids, thus mimicking dietary protein restriction. Here, we sought to further understand the relationship between dietary amino acids and stress tolerance using Drosophila melanogaster. Utilising a chemically defined medium for Drosophila, we found that transiently restricting adult flies of a single essential amino acid generally protects against a lethal dose of the naturally occurring insecticide, nicotine. This protection was conferred during the pre-treatment window, was specific for individual amino acids and depended on the identity of the focal amino acid, as well as the duration and intensity of its restriction. For instance, complete isoleucine deprivation for 7 days maximised its protective effect - increasing survival during nicotine exposure by 100%. However, a dose of 25% threonine was required to maximise its protective effect (53% enhanced survival). To understand the molecular basis of these effects, we modified the signalling of two cellular sensors of amino acids, GCN2 (General control non-derepressible) and mTORC1 (mechanistic Target of Rapamycin Complex 1) in combination with amino acid restriction. We found that GCN2 was necessary for diets to protect against nicotine, whereas suppression of mTORC1 was sufficient to induce nicotine resistance. This finding implies that amino acid restriction acts via amino acid signalling to cross-protect against seemingly unrelated stressors. Altogether, our study offers new insights into the physiological responses to restriction of individual amino acids that confer stress tolerance. This has broad potential for application in animal and human health.

genetics↗

bioRxiv2021

Maternal and paternal sugar consumption interact to modify offspring life history and physiology

Intergenerational effects on offspring phenotypes occur in response to variation in both maternal and paternal nutrition. Because the combined maternal and paternal effects are rarely considered together however, their relative contributions, and the capacity for interactions between parental diets to shape offspring life history and physiology are not understood. To address this, we altered sucrose levels of adult fruit flies (Drosophila melanogaster) prior to mating, across two generations, producing parent-parent and parent-offspring combinations that were either matched or mismatched in dietary sucrose. We then measured lifespan, fecundity, body mass, and triglyceride levels in parents and offspring. We reveal complex non-additive interactions, that involve diets of each parent and offspring to shape offspring phenotypes, but the effects were generally not consistent with an adaptive response to parental diet. Notably, we find that interacting parental flies (sires and dams) lived longer when their sucrose treatments were matched, but they produced shorter-lived offspring.

evolutionary biology↗