Pharmacological targeting of the cancer epigenome.

Epigenetic dysregulation is increasingly appreciated as a hallmark of cancer, including disease initiation, maintenance and therapy resistance. As a result, there have been advances in the development and evaluation of epigenetic therapies for cancer, revealing substantial promise but also challenges. Three epigenetic inhibitor classes are approved in the USA, and many more are currently undergoing clinical investigation. In this Review, we discuss recent developments for each epigenetic drug class and their implications for therapy, as well as highlight new insights into the role of epigenetics in cancer.

Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias.

ABSTRACT: The interaction between menin and histone-lysine N-methyltransferase 2A (KMT2A) is a critical dependency for KMT2A- or nucleophosmin 1 (NPM1)-altered leukemias and an emerging opportunity for therapeutic development. JNJ-75276617 (bleximenib) is a novel, orally bioavailable, potent, and selective protein-protein interaction inhibitor of the binding between menin and KMT2A. In KMT2A-rearranged (KMT2A-r) and NPM1-mutant (NPM1c) acute myeloid leukemia (AML) cells, JNJ-75276617 inhibited the association of the menin-KMT2A complex with chromatin at target gene promoters, resulting in reduced expression of several menin-KMT2A target genes, including MEIS1 and FLT3. JNJ-75276617 displayed potent antiproliferative activity across several AML and acute lymphoblastic leukemia (ALL) cell lines and patient samples harboring KMT2A or NPM1 alterations in vitro. In xenograft models of AML and ALL, JNJ-75276617 reduced leukemic burden and provided a significant dose-dependent survival benefit accompanied by expression changes of menin-KMT2A target genes. JNJ-75276617 demonstrated synergistic effects with gilteritinib in vitro in AML cells harboring KMT2A-r. JNJ-75276617 further exhibited synergistic effects with venetoclax and azacitidine in AML cells bearing KMT2A-r in vitro, and significantly increased survival in mice. Interestingly, JNJ-75276617 showed potent antiproliferative activity in cell lines engineered with recently discovered mutations (MEN1M327I or MEN1T349M) that developed in patients refractory to the menin-KMT2A inhibitor revumenib. A cocrystal structure of menin in complex with JNJ-75276617 indicates a unique binding mode distinct from other menin-KMT2A inhibitors, including revumenib. JNJ-75276617 is being clinically investigated for acute leukemias harboring KMT2A or NPM1 alterations, as a monotherapy for relapsed/refractory acute leukemia (NCT04811560), or in combination with AML-directed therapies (NCT05453903).

Inherent genome instability underlies trisomy 21-associated myeloid malignancies.

Constitutional trisomy 21 (T21) is a state of aneuploidy associated with high incidence of childhood acute myeloid leukemia (AML). T21-associated AML is preceded by transient abnormal myelopoiesis (TAM), which is triggered by truncating mutations in GATA1 generating a short GATA1 isoform (GATA1s). T21-associated AML emerges due to secondary mutations in hematopoietic clones bearing GATA1s. Since aneuploidy generally impairs cellular fitness, the paradoxically elevated risk of myeloid malignancy in T21 is not fully understood. We hypothesized that individuals with T21 bear inherent genome instability in hematopoietic lineages that promotes leukemogenic mutations driving the genesis of TAM and AML. We found that individuals with T21 show increased chromosomal copy number variations (CNVs) compared to euploid individuals, suggesting that genome instability could be underlying predisposition to TAM and AML. Acquisition of GATA1s enforces myeloid skewing and maintenance of the hematopoietic progenitor state independently of T21; however, GATA1s in T21 hematopoietic progenitor cells (HPCs) further augments genome instability. Increased dosage of the chromosome 21 (chr21) gene DYRK1A impairs homology-directed DNA repair as a mechanism of elevated mutagenesis. These results posit a model wherein inherent genome instability in T21 drives myeloid malignancy in concert with GATA1s mutations.

Dynamic joint stiffness in individuals with femoroacetabular impingement syndrome pre- and post-hip arthroscopy.

BACKGROUND: Patients with hip-related pain often fail to return to their desired level of activity following hip arthroscopy. Lasting biomechanics alterations may be one potential explanation. Dynamic joint stiffness assesses the mechanistic controls of the lower limb during high impact movements, and thus, may provide valuable clinical targets to improving movement and optimizing return to activity after surgery. METHODS: Twenty-five participants (13 females) with hip-related pain underwent 3D motion capture during a drop jump task before surgery and six months post-operatively. Nineteen healthy controls (9 females) were collected for comparison. Sagittal plane dynamic joint stiffness was calculated during the initial landing phase. Baseline and 6-month dynamic joint stiffness data were compared 1) between males and females with hip-related pain and 2) between individuals with hip-related pain and controls using Wilcoxon Signed-Rank and Mann Whitney U tests. Sexes were analyzed separately. FINDINGS: From baseline to 6 months post-operatively, females with hip-related pain demonstrated decreased dynamic ankle stiffness (2.26 Nm/deg. [0.61] to 1.84 Nm/deg. [0.43]) (p = .005) and males with hip-related pain demonstrated increased dynamic hip stiffness (2.73 [0.90] to 3.88 [1.73]) (p = .013). There were no differences in dynamic stiffness at any joint between individuals with hip-related pain at either timepoint when compared to controls (p ≥ .099). INTERPRETATION: Females and males with hip-related pain may demonstrate unique changes in dynamic joint stiffness after surgery, indicating return to activity may follow different trajectories for each sex. Additional work should examine the relationship between hip joint stiffness and treatment outcomes and identify additional movement-related rehabilitation targets.

Assessing reliability and validity of SIPAT and opportunities for improvement: A single-center cohort study.

Psychosocial assessment is a standard component of patient evaluations for transplant candidacy. The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a widely used measure to assess psychosocial risk for transplant. However, there are questions regarding the SIPAT's reliability and validity. We examined the SIPAT's psychometric performance and its impact on equitable access to transplant in a diverse cohort of 2825 patients seeking liver transplantation between 2014 and 2021 at an urban transplant center. The SIPAT demonstrated good internal consistency reliability at the overall score [Cronbach's α = 0.85, 95% CI (0.83, 0.86)] and domain levels (0.80 > α > 0.70). There was mixed support for structural validity, with poor overall model fit in confirmatory factor analysis and 50% of questions achieving the 0.70-factor loadings threshold. Adjusting for sociodemographic variables, the odds of not being waitlisted for psychosocial reasons were three times higher for patients with Medicaid insurance than patients with private insurance [OR 3.24, 95% CI (2.09, 4.99)] or Medicare [OR 2.89, 95% CI (1.84, 4.53)], mediated by higher SIPAT scores. Black patients had nearly twice the odds of White patients [OR 1.88, 95% CI (1.20, 2.91)], partially mediated by higher social support domain scores. Patients with Medicaid, non-White patients, and those without a college degree scored significantly higher on collinear questions, disproportionately contributing to higher SIPAT scores. The SIPAT did not perform equally across insurance type, race/ethnicity, and education groups, with the lowest subgroup validity associated with patient readiness and psychopathology domains. The SIPAT should be interpreted with caution, especially as a composite score. Future studies should examine validity in other populations.

Mezigdomide is effective alone and in combination with menin inhibition in preclinical models of KMT2A-r and NPM1c AML.

ABSTRACT: Small molecules that target the menin-KMT2A protein-protein interaction (menin inhibitors) have recently entered clinical trials in lysine methyltransferase 2A (KMT2A or MLL1)-rearranged (KMT2A-r) and nucleophosmin-mutant (NPM1c) acute myeloid leukemia (AML) and are demonstrating encouraging results. However, rationally chosen combination therapy is needed to improve responses and prevent resistance. We have previously identified IKZF1/IKAROS as a target in KMT2A-r AML and shown in preclinical models that IKAROS protein degradation with lenalidomide or iberdomide has modest single-agent activity yet can synergize with menin inhibitors. Recently, the novel IKAROS degrader mezigdomide was developed with greatly enhanced IKAROS protein degradation. In this study, we show that mezigdomide has increased preclinical activity in vitro as a single-agent in KMT2A-r and NPM1c AML cell lines, including sensitivity in cell lines resistant to lenalidomide and iberdomide. Further, we demonstrate that mezigdomide has the greatest capacity to synergize with and induce apoptosis in combination with menin inhibitors, including in MEN1 mutant models. We show that the superior activity of mezigdomide compared with lenalidomide or iberdomide is due to its increased depth, rate, and duration of IKAROS protein degradation. Single-agent mezigdomide was efficacious in 5 patient-derived xenograft models of KMT2A-r and 1 NPM1c AML. The combination of mezigdomide with the menin inhibitor VTP-50469 increased survival and prevented and overcame MEN1 mutations that mediate resistance in patients receiving menin inhibitor monotherapy. These results support prioritization of mezigdomide for early phase clinical trials in KMT2A-r and NPM1c AML, either as a single agent or in combination with menin inhibitors.

Females with hip-related pain demonstrate reduced kinetics at the hip and ankle during terminal stance of gait.

BACKGROUND: Individuals with hip-related pain (HRP) commonly report pain with walking and demonstrate altered movement patterns compared to healthy controls (HCs). Individuals with HRP may attempt to reduce pain during walking by decreasing kinetics and joint forces at the hip through increased use of the ankle during pushoff. RESEARCH QUESTION: Do individuals with HRP have increased kinetics at the ankle and decreased kinetics at the hip during pushoff in gait compared to HCs, and do kinetic patterns differ between males and females with HRP? METHODS: This retrospective observational study included 42 individuals with HRP and 20 HCs. Participants completed overground gait trials at their self-selected speed while kinematics and kinetics were recorded through a motion capture system and force plates. Peak internal hip and ankle moments and hip flexion and ankle plantarflexion angular impulse during terminal stance were used in general estimating equations for comparison of group by limb interactions for males and females separately, as well as a comparison of males and females within the HRP group. RESULTS: Females with HRP demonstrated reduced hip flexion impulse on their involved limb (.070 Nm*s/kg*m) compared to female HCs (.083Nm*s/kg*m; p = .032), as well as reduced peak ankle plantarflexion moment (-.94Nm/kg*m) compared to their contralateral limb (-.99Nm/kg*m) and the involved limb of HRP males (-1.00Nm/kg*m) (p ≤ .007). There were no between-limb or between-group differences in hip or ankle peak moments or impulses in males. SIGNIFICANCE: Females with HRP show decreased kinetics at both the hip and ankle; these patterns were not identified in males. Future investigations should examine whether increasing ankle kinetics during pushoff reduces pain at the hip, as this may be a valuable clinical treatment strategy.

Survival of Inoculated Vibrio spp., Shigatoxigenic Escherichia coli, Listeria monocytogenes, and Salmonella spp. on Seaweed (Sugar Kelp) During Storage.

Bacteria including Vibrio spp. persist in coastal waters and can contaminate edible seaweeds. Pathogens such as Listeria monocytogenes, shigatoxigenic Escherichia coli (STEC), and Salmonella have been associated with and present serious health risks in minimally processed vegetables including seaweeds. This study evaluated the survival of four pathogens inoculated onto two product forms of sugar kelp subjected to different storage temperatures. The inoculation comprised of a cocktail of two Listeria monocytogenes and STEC strains, two Salmonella serovars, and two Vibrio species. STEC and Vibrio were grown and applied in salt-containing media to simulate preharvest contamination, whereas L. monocytogenes and Salmonella inocula were prepared to simulate postharvest contamination. Samples were stored at 4°C and 10°C for 7 days, and 22°C for 8 h. Microbiological analyses were performed periodically (1, 4, 8, 24 h, etc.) to evaluate the effects of storage temperature on pathogen survival. Pathogen populations decreased under all storage conditions, but survival was greatest for all species at 22°C, with STEC exhibiting significantly less reduction (1.8 log CFU/g) than Salmonella, L. monocytogenes, and Vibrio (3.1, 2.7, and 2.7 log CFU/g, respectively) after storage. The largest population reduction (5.3 log CFU/g) was observed in Vibrio stored at 4°C for 7 days. Regardless of storage temperature, all pathogens remained detectable at the end of the study duration. Results emphasize the need for strict adherence to temperature control for kelp as temperature abuse may support pathogen survival, especially STEC, during storage, and the need for prevention of postharvest contamination, particularly with Salmonella.

A novel image-based method for simultaneous counting of Lactobacillus and Saccharomyces in mixed culture fermentation.

Mixed microorganism cultures are prevalent in the food industry. A variety of microbiological mixtures have been used in these unique fermenting processes to create distinctive flavor profiles and potential health benefits. Mixed cultures are typically not well characterized, which may be due to the lack of simple measurement tools. Image-based cytometry systems have been employed to automatically count bacteria or yeast cells. In this work, we aim to develop a novel image cytometry method to distinguish and enumerate mixed cultures of yeast and bacteria in beer products. Cellometer X2 from Nexcelom was used to count of Lactobacillus plantarum and Saccharomyces cerevisiae in mixed cultures using fluorescent dyes and size exclusion image analysis algorithm. Three experiments were performed for validation. (1) Yeast and bacteria monoculture titration, (2) mixed culture with various ratios, and (3) monitoring a Berliner Weisse mixed culture fermentation. All experiments were validated by comparing to manual counting of yeast and bacteria colony formation. They were highly comparable with ANOVA analysis showing p-value > 0.05. Overall, the novel image cytometry method was able to distinguish and count mixed cultures consistently and accurately, which may provide better characterization of mixed culture brewing applications and produce higher quality products.

The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia.

Targeting critical epigenetic regulators reverses aberrant transcription in cancer, thereby restoring normal tissue function1-3. The interaction of menin with lysine methyltransferase 2A (KMT2A), an epigenetic regulator, is a dependence in acute leukaemia caused by either rearrangement of KMT2A or mutation of the nucleophosmin 1 gene (NPM1)4-6. KMT2A rearrangements occur in up to 10% of acute leukaemias and have an adverse prognosis, whereas NPM1 mutations occur in up to 30%, forming the most common genetic alteration in acute myeloid leukaemia7,8. Here, we describe the results of the first-in-human phase 1 clinical trial investigating revumenib (SNDX-5613), a potent and selective oral inhibitor of the menin-KMT2A interaction, in patients with relapsed or refractory acute leukaemia (ClinicalTrials.gov, NCT04065399). We show that therapy with revumenib was associated with a low frequency of grade 3 or higher treatment-related adverse events and a 30% rate of complete remission or complete remission with partial haematologic recovery (CR/CRh) in the efficacy analysis population. Asymptomatic prolongation of the QT interval on electrocardiography was identified as the only dose-limiting toxicity. Remissions occurred in leukaemias refractory to multiple previous lines of therapy. We demonstrate clearance of residual disease using sensitive clinical assays and identify hallmarks of differentiation into normal haematopoietic cells, including differentiation syndrome. These data establish menin inhibition as a therapeutic strategy for susceptible acute leukaemia subtypes.

Sexual selection and the evolution of condition-dependence: an experimental test at two resource levels.

Stronger condition-dependence in sexually selected traits is well-documented, but how this relationship is established remains unknown. Moreover, resource availability can shape responses to sexual selection, but resource effects on the relationship between sexual selection and condition-dependence are also unknown. In this study, we directly test the hypotheses that sexual selection drives the evolution of stronger-condition-dependence and that resource availability affects the outcome, by evolving fruit flies (Drosophila melanogaster) under relatively strong or weak sexual selection (through varied sex ratios) and at resource-poor or resource-rich adult diets. We then experimentally manipulated condition via developmental diet and assessed condition-dependence in adult morphology, behavior, and reproduction. We observed stronger condition-dependence in female size in male-biased populations and in female ovariole production in resource-limited populations. However, we found no evidence that male condition-dependence increased in response to sexual selection, or that responses depended on resource levels. These results offer no support for the hypotheses that sexual selection increases male condition-dependence or that sexual selection's influence on condition-dependence is influenced by resource availability. Our study is, to our knowledge, the first experimental test of these hypotheses. If the results we report are general, then sexual selection's influence on the evolution of condition-dependence may be less important than predicted.

The Maintenance of the U.S. Racial Hierarchy Through Judgments of Multiracial People Based on Proximity to Whiteness.

Previous research has argued that a growing multiracial population will blur boundaries between racial groups, reducing racism and improving interracial relations. However, this is unlikely to happen if multiracial groups are judged according to their proximity to Whiteness. We examined how having White ancestry shapes status perceptions of multiracial groups. Studies 1 and 2 showed that multiracial groups with White ancestry (e.g., Black/White) are considered higher status than dual minority multiracial (e.g., Black/Latinx) and monoracial minority (e.g., Black) groups. Study 3 revealed that multiracial groups with White ancestry are perceived as more competent and warmer than monoracial minority and dual minority multiracial groups, leading to higher status perceptions for multiracial groups with White ancestry. Thus, multiracial people, like other racial minorities, may be judged according to White, Eurocentric standards. The results imply that, without anti-racist intervention, the treatment of multiracial people will reinforce, rather than challenge, the existing racial hierarchy.

Females with hip-related pain display altered lower limb mechanics compared to their healthy counterparts in a drop jump task.

BACKGROUND: Hip-related pain describes femoroacetabular impingement syndrome, acetabular dysplasia, and other hip pain conditions without clear morphological features. Movement strategies in this population, notably sex-related patterns, are poorly understood and may provide insights into why females report more pain and worse function. This study examined the sex-related differences during a drop vertical jump task between those with hip-related pain and healthy controls. METHODS: Patients with hip-related pain and healthy controls completed five repetitions of a drop jump while their kinematics and kinetics were recorded using a motion capture system and force plates. Hip, knee, and ankle joint angles and external joint moments during landing were used in general estimating equations for comparison of group by sex by limb interactions. Time series data were further investigated using statistical parametric mapping. FINDINGS: Females with hip-related pain had 9.1° less hip flexion (P = .041) and 9.2° less knee flexion (P = .024) than healthy females, and 8.3° less knee flexion than male counterparts with hip-related pain (P = .039). Males demonstrated 1.4° less hip flexion on the affected side compared to their uninvolved side (P = .004). Statistical parametric mapping results showed significant differences in knee flexion angle for females with hip-related pain compared to healthy females (P = .042). There were no significant differences in hip, knee, or ankle moments. INTERPRETATION: Females with hip-related pain showed kinematic patterns distinct from healthy controls. Sex may be an important variable of interest in characterizing movement impairments in this population and movement impairments may be an appropriate target for intervention for these patients.

Technological risks and ethical implications of using robots in long-term care.

Introduction: The pandemic provides a unique opportunity to examine new directions in innovative technological approaches in long-term care (LTC) homes. While robotics could enhance staff capacity to provide care, there are potential technology risks and ethical concerns involved in technology use among older people residing in communal aged care homes. This qualitative descriptive study explores the technological risks and ethical issues associated with the adoption of robots in the specific context of LTC homes. Methods: The research team including patient and family partners employed purposive and snowballing methods to recruit 30 LTC participants: frontline interdisciplinary staff, operational leaders, residents and family members, and ethics experts in dementia care. Semi-structured interviews were conducted. Thematic analysis was performed to identify themes that capture empirical experiences and perspectives of a diverse group of LTC stakeholders about robotic use. Results: Technological risks include safety, increased workload, privacy, cost and social justice, and human connection. The findings offer practical insights based on the LTC perspective to contribute to the robot ethics literature. We propose a list of pragmatic recommendations, focusing on six principles (ETHICS): Engagement of stakeholders, Technology benefit and risk assessment, Harm mitigation, Individual autonomy, Cultural safety and justice, Support of privacy. Conclusions: There is both a growing interest as well as fear in using robotics in LTC. Practice leaders need to reflect on ethical considerations and engage relevant stakeholders in making technology decisions for everyday care.

Experimental evolution under varying sex ratio and nutrient availability modulates male mating success in Drosophila melanogaster.

Biased population sex ratios can alter optimal male mating strategies, and allocation to reproductive traits depends on nutrient availability. However, there is little information on how nutrition interacts with sex ratio to influence the evolution of pre-copulatory and post-copulatory traits separately. To address this omission, we test how male mating success and reproductive investment evolve under varying sex ratios and adult diet in Drosophila melanogaster, using experimental evolution. We found that sex ratio and nutrient availability interacted to determine male pre-copulatory performance. Males from female-biased populations were slow to mate when they evolved under protein restriction. By contrast, we found direct and non-interacting effects of sex ratio and nutrient availability on post-copulatory success. Males that evolved under protein restriction were relatively poor at suppressing female remating. Males that evolved under equal sex ratios fathered more offspring and were better at supressing female remating, relative to males from male-biased or female-biased populations. These results support the idea that sex ratios and nutrition interact to determine the evolution of pre-copulatory mating traits, but independently influence the evolution of post-copulatory traits.

Unleashing Cell-Intrinsic Inflammation as a Strategy to Kill AML Blasts.

Leukemic blasts are immune cells gone awry. We hypothesized that dysregulation of inflammatory pathways contributes to the maintenance of their leukemic state and can be exploited as cell-intrinsic, self-directed immunotherapy. To this end, we applied genome-wide screens to discover genetic vulnerabilities in acute myeloid leukemia (AML) cells implicated in inflammatory pathways. We identified the immune modulator IRF2BP2 as a selective AML dependency. We validated AML cell dependency on IRF2BP2 with genetic and protein degradation approaches in vitro and genetically in vivo. Chromatin and global gene-expression studies demonstrated that IRF2BP2 represses IL1ß/TNFα signaling via NFκB, and IRF2BP2 perturbation results in an acute inflammatory state leading to AML cell death. These findings elucidate a hitherto unexplored AML dependency, reveal cell-intrinsic inflammatory signaling as a mechanism priming leukemic blasts for regulated cell death, and establish IRF2BP2-mediated transcriptional repression as a mechanism for blast survival. SIGNIFICANCE: This study exploits inflammatory programs inherent to AML blasts to identify genetic vulnerabilities in this disease. In doing so, we determined that AML cells are dependent on the transcriptional repressive activity of IRF2BP2 for their survival, revealing cell-intrinsic inflammation as a mechanism priming leukemic blasts for regulated cell death. See related commentary by Puissant and Medyouf, p. 1617. This article is highlighted in the In This Issue feature, p. 1599.

The evolution of sex peptide: sexual conflict, cooperation, and coevolution.

A central paradigm in evolutionary biology is that the fundamental divergence in the fitness interests of the sexes ('sexual conflict') can lead to both the evolution of sex-specific traits that reduce fitness for individuals of the opposite sex, and sexually antagonistic coevolution between the sexes. However, clear examples of traits that evolved in this way - where a single trait in one sex demonstrably depresses the fitness of members of the opposite sex, resulting in antagonistic coevolution - are rare. The Drosophila seminal protein 'sex peptide' (SP) is perhaps the most widely cited example of a trait that appears to harm females while benefitting males. Transferred in the ejaculate by males during mating, SP triggers profound and wide-ranging changes in female behaviour and physiology. Early studies reported that the transfer of SP enhances male fitness while depressing female fitness, providing the foundations for the widespread view that SP has evolved to manipulate females for male benefit. Here, we argue that this view is (i) a simplification of a wider body of contradictory empirical research, (ii) narrow with respect to theory describing the origin and maintenance of sexually selected traits, and (iii) hard to reconcile with what we know of the evolutionary history of SP's effects on females. We begin by charting the history of thought regarding SP, both at proximate (its production, function, and mechanism of action) and ultimate (its fitness consequences and evolutionary history) levels, reviewing how studies of SP were central to the development of the field of sexual conflict. We describe a prevailing paradigm for SP's evolution: that SP originated and continues to evolve to manipulate females for male benefit. In contrast to this view, we argue on three grounds that the weight of evidence does not support the view that receipt of SP decreases female fitness: (i) results from studies of SP's impact on female fitness are mixed and more often neutral or positive, with fitness costs emerging only under nutritional extremes; (ii) whether costs from SP are appreciable in wild-living populations remains untested; and (iii) recently described confounds in genetic manipulations of SP raise the possibility that measures of the costs and benefits of SP have been distorted. Beyond SP's fitness effects, comparative and genetic data are also difficult to square with the idea that females suffer fitness costs from SP. Instead, these data - from functional and evolutionary genetics and the neural circuitry of female responses to SP - suggest an evolutionary history involving the evolution of a dedicated SP-sensing apparatus in the female reproductive tract that is likely to have evolved because it benefits females, rather than harms them. We end by exploring theory and evidence that SP benefits females by functioning as a signal of male quality or of sperm receipt and storage (or both). The expanded view of the evolution of SP that we outline recognises the context-dependent and fluctuating roles played by both cooperative and antagonistic selection in the origin and maintenance of reproductive traits.

A resource-poor developmental diet reduces adult aggression in male Drosophila melanogaster.

Aggressive behaviours occur throughout the animal kingdom and agonistic contests often govern access to resources. Nutrition experienced during development has the potential to influence aggressive behaviours in adults through effects on growth, energy budgets and an individual's internal state. In particular, resource-poor developmental nutrition might decrease adult aggression by limiting growth and energy budgets, or alternatively might increase adult aggression by enhancing motivation to compete for resources. However, the direction of this relationship-and effects of developmental nutrition experienced by rivals-remains unknown in most species, limiting understanding of how early-life environments contribute to variation in aggression. We investigated these alternative hypotheses by assessing male-male aggression in adult fruit flies, Drosophila melanogaster, that developed on a low-, medium- or high-resource diet, manipulated via yeast content. We found that a low-resource developmental diet reduced the probability of aggressive lunges in adults, as well as threat displays against rivals that developed on a low-resource diet. These effects appeared to be independent of diet-related differences in body mass. Males performed relatively more aggression on a central food patch when facing rivals of a low-resource diet, suggesting that developmental diet affects aggressive interactions through social effects in addition to individual effects. Our finding that resource-poor developmental diets reduce male-male aggression in D. melanogaster is consistent with the idea that resource budgets mediate aggression and in a mass-independent manner. Our study improves understanding of the links between nutrition and aggression. Significance statement Early-life nutrition can influence social behaviours in adults. Aggression is a widespread social behaviour with important consequences for fitness. Using the fruit fly, Drosophila melanogaster, we show that a poor developmental diet reduces aspects of adult aggressive behaviour in males. Furthermore, males perform more aggression near food patches when facing rivals of poor nutrition. This suggests that early-life nutrition affects aggressive interactions through social effects in addition to individual effects. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00265-021-03050-z.

Impact of Blanching, Freezing, and Fermentation on Physicochemical, Microbial, and Sensory Quality of Sugar Kelp (Saccharina latissima).

Low seaweed consumption in the West is due to lack of availability and consumer familiarity. In this study, the effects of preservation processes on quality aspects of Saccharina latissima products were assessed. First, a blanching (100 °C for 1 or 3 min) treatment was used to produce seaweed salad. In a second study, effects of blanching, freezing, and fermentation on kelp quality were assessed and processed kelp was used to produce sauerkraut. Blanching significantly decreased (p ≤ 0.05) the instrumental kelp a* value and firmness. The a* value negatively correlated with overall liking of salads. To prepare sauerkraut, raw, raw/frozen (-20 °C), blanched (100 °C, 1 min), or blanched/frozen kelp were mixed with cabbage, salted, inoculated with starter cultures and fermented. Inconsistent trends in L* values, firmness, and fungi enumeration were observed after fermentation. Consumers evaluated kelp salad (n = 100) and sauerkraut (n = 80) for acceptability. Blanched kelp salad had higher hedonic scores than raw kelp salad. A 100% cabbage sauerkraut control and blanched kelp/cabbage blends were compared; kelp blends were similar to control for appearance, color, and texture but were lower for overall acceptability. Results suggest improved quality and enhanced consumer acceptability of seaweed products with use of minimal processing.