Offspring Generation Research Articles

Exercise Alters FBF1-Regulated Novel-miRNA-1135 Associated with Hydrolethalus Syndrome 1 in Rheumatoid Arthritis: A Preliminary Study.

Hydrolethalus Syndrome 1 (HYDS1) is a rare disorder that occurs commonly in Finnish infants but originates from the mother. This autosomal recessive syn-drome is associated with the FBF1, which is usually expressed in the centriole. The FBF1 is an inheritable arthritis disease phenotype that includes rheumatoid arthritis. Several studies have investigated males with FBF1 mutation carriers also related to arthritis diseases, including those under rheumatoid arthritis conditions, which revealed the possibility of conferring the gene mutation to the next generation of offspring. Nonetheless, there are some complications of FBF1 mutation with target miRNAs that can be affected by exercise. The objective of this study was to evaluate the different exercises that can be utilized to suppress the FBF1 mutation targeted by Novel-rno-miRNAs-1135 as a biomarker and assess the effectiveness of exercise in mitigating the FBF1 mutation. Four exercise interventional groups were divided into exercise and non-exercise groups. One hundred microliter pristane-induced arthritis (PIA) was injected at the dorsal re-gion of the tails of rodents and introduced to the two PIA interventional groups. On day forty-five, all animals were euthanized, and total RNA was extracted from the blood samples of ro-dents, while polymerase chain reaction (PCR) was amplified by using 5-7 primers. Computeri-zation was used for miRNA regulation and analysis of target gene candidates. The novel-rno-miRNA-1135 was downregulated to FBF1 in exercise groups. The exercise was found to have no significant impact in terms of change in novel-rno-miRNA-1135 regulation of FBF1 expression. Exercise has no impact on novel-rno-miRNA-1135 targeted for FBF1 in autoso-mal recessive disease.

A population hierarchical-based evolutionary algorithm for large-scale many-objective optimization

In large-scale many-objective optimization problems (LMaOPs), the performance of algorithms faces significant challenges as the number of objective functions and decision variables increases. The main challenges in addressing this type of problem are as follows: the large number of decision variables creates an enormous decision space that needs to be explored, leading to slow convergence; and the high-dimensional objective space presents difficulties in selecting dominant individuals within the population. To address this issue, this paper introduces an evolutionary algorithm based on population hierarchy to address LMaOPs. The algorithm employs different strategies for offspring generation at various population levels. Initially, the population is categorized into three levels by fitness value: poorly performing solutions with higher fitness (Ph), better solutions with lower fitness (Pl), and excellent individuals stored in the archive set (Pa). Subsequently, a hierarchical knowledge integration strategy (HKI) guides the evolution of individuals at different levels. Individuals in Pl generate offspring by integrating differential knowledge from Pa and Ph, while individuals in Ph generate offspring by learning prior knowledge from Pa. Finally, using a cluster-based environment selection strategy balances population diversity and convergence. Extensive experiments on LMaOPs with up to 10 objectives and 5000 decision variables validate the algorithm’s effectiveness, demonstrating superior performance.

Association of vertebral fractures with worsening degenerative changes of the spine: a longitudinal study.

Vertebral compression fractures (VFs) and spinal degeneration are both common causes of back pain, particularly in older adults. Previous cross-sectional studies have shown a potential association between these entities, but there is limited evidence on the role of VFs in spinal degeneration. In this longitudinal study, we evaluated the association between prevalent VFs and the subsequent progression of facet joint osteoarthritis (FJOA) and intervertebral disc height narrowing (DHN), using data from the Framingham Heart Study Offspring and Third Generation Multi-Detector Computed Tomography study. Summary indices representing the total burden of each spinal parameter (VFs, DHN and FJOA) were calculated for each individual. We hypothesized that prevalent VFs are associated with worsening spinal degeneration. 370 (31%) of 1197 participants, had a baseline (prevalent) VF. The change in summary index of DHN over the follow-up period was significantly higher in those with versus without prevalent VF (difference in change in DHN 0.38, 95% CI 0.18 to 0.59, P<.001), but the change in summary index of FJOA was similar between those with and without prevalent VF. However, once adjusted for age, sex, cohort, smoking status, body mass index, and baseline DHN, the change in summary index of DHN did not differ by prevalent VF status. There was a modestly higher change in the FJOA summary index in those with prevalent VFs compared to those without in the fully adjusted model (difference in change in FJOA 0.62, 95% CI -0.01 to 1.24, P=.054), driven primarily by those with severe (grade 3) VF (difference in change in FJOA 4.48, 95% CI 1.99 to 6.97). Moreover, there was greater change in the summary index of FJOA with increasing severity of prevalent VF (linear trend P=.005). Beyond the established morbidity and mortality associated with VFs, our study suggests that VFs may also lead to worsening spine osteoarthritis.

Heat Stress Inhibits Pollen Development by Degrading mRNA Capping Enzyme ARCP1 and ARCP2.

Pollen development and germination are critical for successful generation of offspring in plants, yet they are highly susceptible to heat stress (HS). However, the molecular mechanism underlying this process has not been fully elucidated. In this study, we highlight the essential roles of two mRNA capping enzymes, named Arabidopsis mRNA capping phosphatase (ARCP) 1 and 2, in regulating male and female gamete development. The transmission efficiencies of gametes carrying arcp1 arcp2 from arcp1+/- arcp2-/- and arcp1-/- arcp2+/- mutants are 30% and zero, respectively. These mutants exhibited a significant increase in misshaped pollen, with germination rates approximately half of those in wild type. ARCP1/2 exhibit RNA triphosphatase and RNA guanylyltransferase activities, which are required for proper pollen development. Through RNA-seq analysis, genes involved in pollen development/germination and HS response were identified as downregulated genes in pollen from arcp1+/- arcp2-/- mutant. Furthermore, ARCP2 protein is degraded under HS condition, and inducing the expression of ARCP2 can increase the pollen germination rate under elevated temperature. We propose that HS triggers the degradation of mRNA capping enzymes, which in turn disrupts the transcriptome that required for pollen development and pollen germination and ultimately leads to male sterility.

Eggs, dietary choline, and nonalcoholic fatty liver disease in the Framingham Heart Study

BackgroundEggs are rich in bioactive compounds, including choline and carotenoids, that may benefit cardiometabolic outcomes. However, little is known about their relation with nonalcoholic fatty liver disease (NAFLD). ObjectiveWe investigated the association between intakes of eggs and selected egg-rich nutrients (choline, lutein and zeaxanthin) and NAFLD risk and changes in liver fat over approximately 6 years of follow-up in the Framingham Offspring and Third Generation cohorts. MethodsOn two separate occasions (2002–2005 and 2008–2011), liver fat was assessed using a computed tomography scan to estimate the average liver fat attenuation relative to a control phantom to create the liver phantom ratio (LPR). In 2008-2011, cases of incident NAFLD were identified as an LPR ≤0.33 in the absence of heavy alcohol use, after excluding prevalent NAFLD (LPR ≤0.33) in 2002–2005. Food frequency questionnaires were used to estimate egg intakes (classified as <1, 1, and ≥2 per week) and dietary choline (adjusted for body weight using the residual method), and the combined intakes of lutein and zeaxanthin. Multivariable modified Poisson regression and general linear models were used to compute incident risk ratios (RR) of NAFLD and adjusted mean annualized liver fat change. ResultsNAFLD cumulative incidence was 19% among a total of 1414 participants. We observed no associations between egg intake or the combined intakes of lutein and zeaxanthin with an incident NAFLD risk or liver fat change. Other diet and cardiometabolic risk factors did not modify this association. However, dietary choline intakes were inversely associated with NAFLD risk (RR for tertile 3 vs. 1: 0.69, 95% CI: 0.51–0.94). ConclusionsWhile egg intake was not directly associated with NAFLD risk, eggs are a major source of dietary choline, which was strongly inversely associated with NAFLD risk in this community-based cohort.

Effects of progesterone administered to maternal rats during the teratogenesis-sensitive period through different routes on neurobehavior and gut microbiota in offspring

Objective: Progesterone (P4) is the optimal agent for luteal support in assisted reproductive technologies. Despite the availability of various formulations, the impacts of P4 treatment administered through different routes on offspring growth remain unevaluated. This study aimed to investigate and compare the effects of P4 administration through three different routes in pregnant rats during the teratogenesis-sensitive period on fertility outcomes and the behavior, plasma P4 and pregnenolone levels, and alterations in gut microbiota in the filial generation (F1) of offspring. Methods: Female rats that mated successfully were randomly classified into four groups: Group 1, the normal control group; Group 2, the IG group, in which utrogestan was administered via intragastric gavage; Group 3, the IM group, in which P4 was administered via intramuscular injection; and Group 4, the VAGIN group, in which P4 sustained-release vaginal gel was administered through the vagina. Except for the control group, P4 was administered in other groups through their respective routes for 13 consecutive days daily during the teratogenic-sensitive gestation period (days 6–18). The fertility outcomes of the maternal rats were observed, and open-field and three-chamber social preference tests were conducted to assess anxiety and social behavior, along with an exhaustive swimming experiment to evaluate the motor endurance of the offspring. Plasma P4 and pregnenolone levels in the offspring were measured, and fecal samples were assessed using gut microbiota sequencing and subsequent bioinformatics analysis. Results: No significant alterations in fertility outcomes were observed through three P4 administration routes—intragastric gavage, intramuscular injection, and vaginal administration—in rats. However, in behavioral experiments in offspring, a significant increase was observed in swimming time in the IG group than in the control group (P = 0.013). Furthermore, the offspring in the IG group exhibited a marked decrease in non-social behaviors compared with the control group (P = 0.030). No significant behavioral changes were observed in the F1 offspring in the open-field test. Additionally, the offspring in the IG group exhibited a significant elevation in plasma pregnenolone levels compared with the control group (P = 0.019) 30 days after birth. No notable differences in the α-diversity of gut microbiota were observed among the groups. However, significant differences in β-diversity were observed in both the IG and IM groups compared with the control group, indicating that P4 treatment via the two routes exhibited a significant impact on the gut microbiota composition of F1 offspring. Distinct differences were observed in the gut microbiota of the offspring among the three P4 treatment groups, with 22, 28, and 33 differential bacterial taxa identified in the IG, IM, and VAGIN groups, respectively, using linear discriminant effect size analysis, whereas Olivella appeared exclusively in the control group rather than in the P4 treatment groups. Conclusion: Oral administration of P4 to maternal rats during the teratogenesis-sensitive period enhanced motor endurance and plasma pregnenolone levels and altered the composition of the gut microbiota in the offspring. Our findings demonstrated different effects on offspring growth when P4 is administered orally, intramuscularly, or vaginally.

An Improved Coevolutionary Algorithm for Constrained Multi-Objective Optimization Problems

Constrained multi-objective optimization problems are ubiquitous in engineering applications. In recent years, constrained multi-objective optimization algorithms based on the dual population coevolutionary framework have been widely studied due to their excellent performance. However, when facing optimization problems with complex constraints, the performance of existing algorithms still needs further improvement. This paper proposes an improved constrained multi-objective coevolutionary algorithm (iCMOCA). The algorithm mainly includes two populations: One population takes into account constraints, while the other population disregards them. Meanwhile, the iCMOCA employs effective collaboration between two populations during the process of offspring generation and environmental selection, and it utilizes an environmental selection strategy based on multi-objective to multi-objective decomposition to improve the performance. Comparative analysis conducted on the DAS-CMOP and MW test suites provides empirical evidence that iCMOCA outperforms five state-of-the-art algorithms.

Deep reinforcement learning assisted novelty search in Voronoi regions for constrained multi-objective optimization

Solving constrained multi-objective optimization problems (CMOPs) requires optimizing multiple conflicting objectives while satisfying various constraints. Existing constrained multi-objective evolutionary algorithms (CMOEAs) cross infeasible regions by ignoring constraints. However, these methods might neglect promising search directions, leading to insufficient exploration of the search space. To address this issue, this paper proposes a deep reinforcement learning assisted constrained multi-objective quality-diversity algorithm. The proposed algorithm designs a diversity maintenance mechanism to promote evenly coverage of the final solution set on the constrained Pareto front. Specifically, first, a novelty-oriented archive is created using a centroid Voronoi tessellation, which divides the search space into a desired number of Voronoi regions. Each region acts as a repository of non-dominated solutions with different phenotypic characteristics to provide diversity information and supplementary evolutionary trails. Secondly, to improve resource utilization, a deep Q-network is adopted to learn a policy to select suitable Voronoi regions for offspring generation based on their novelty scores. The exploration of these regions aims to find a set of diverse, high-performing solutions to accelerate convergence and escape local optima. Compared with eight state-of-the-art CMOEAs, experimental studies on four benchmark suites and nine real-world applications demonstrate that the proposed algorithm exhibits superior or at least competitive performance, especially on problems with discrete and narrow feasible regions.

Multi-branch evolutionary generative adversarial networks based on covariance crossover operators

Generative Adversarial Networks (GANs) have brought surprises in image generation and processing, particularly excelling in alleviating the problem of sparse samples in few-shot learning. Evolutionary Generative Adversarial Networks (EGANs) aim to convert the generation task into an optimization problem by integrating multiple loss functions to minimize the gap between the generated distribution and the data distribution. However, EGANs’ heavy reliance on mutation operations introduces excessive randomness, resulting in unstable generator updates and affecting the diversity of generated samples. This leads to challenges such as model collapse and gradient vanishing. In this paper, inspired by human grafting mechanism, we propose a novel Multi-branch Evolutionary Generative Adversarial Network (ME-GAN) based covariance crossover operator, which includes two distinct branches – Evolutionary GAN (E-GAN) and Conditional Evolutionary GAN (CE-GAN). Specifically, the E-GAN branch involves a mutation process to introduce randomness to the generated samples, while the CE-GAN branch aims to provide more realistic and diversify generated samples through conditional enhancement and relevant mutation processes. We propose a crossover operation that utilizes the covariance similarity metric to transfer different feature attributes between offspring of different generations, thereby generating a diverse sample. Extensive experiments on CIFAR-10, STL-10, and CelebA datasets demonstrate the effectiveness and superiority of the proposed framework.

Anastatus japonicus Ashmead, a potential biological control agent of Riptortus pedestris (Fabricius)

Riptortus pedestris (Fabricius) (Hemiptera: Alydidae) is a significant pest of soybean production in China. While biological control would be a desirable means to manage this pest, little research on the use of parasitoids against R. pedestris has been done. In this study, for the parasitoid Anastatus japonicus Ashmead (Hymenoptera: Eupelmidae), we measured the parasitism rate in R. pedestris, the emergence rate of parasitoid progeny, and mortality of eggs from host-feeding. Parasitoids of different ages were assessed against R. pedestris eggs of various ages under laboratory conditions. In addition, the development and longevity of A. japonicus reared on R. pedestris egg were also measured. We found the maximum parasitism rate of A. japonicus was 54.6% on R. pedestris egg. And the maximum emergence rate of A. japonicus was 50.0% from all offered R. pedestris eggs. Mortality from parasitoid host-feeding was 43.8% when 1-day-old R. pedestris eggs were offered to 6-day-old A. japonicus parasitoids. For older eggs, parasitism rates were lower, making 1-day old eggs the optimal host age for use in mass rearing. Longevity of the offspring (F1) generation of A. japonicus were 10 (males) and 23 (females) days. The developmental times of the F1 offspring were 21.9 (males) and 21.7 (females) days. The parasitism rate and the rate of mortality due to host feeding caused by parasitoid progeny (F1) generation were 56.3, and 43.8%, respectively. Among all the eggs parasitized not subjected to host feeding, 98.5% yielded adult parasitoids. Among all emerging A. japonicus, the sex ratio (as % female) in the F2 generation was 45%, which was significantly higher than that in the first generation (F1) (18%). These results suggest that A. japonicus could be a potential biological control agent for use against R. pedestris.

PSVI-14 Effects of poor maternal nutrition during gestation on first generation offspring oxidative status in skeletal muscle

Abstract Poor maternal nutrition (restricted- and over-nutrition) during gestation negatively impacts offspring pre- and post-natal growth. Previous work has identified decreased muscle mass and increased adiposity, leading to poor quantity and quality of animal protein products. Alterations in oxidative status, such as the imbalance of antioxidant activity and the production of free radicals, can result in oxidative stress damaging lipid membranes, proteins, and DNA. Changes in oxidative status may contribute to the poor growth outcomes observed in offspring from poorly nourished dams. Therefore, the objective of this research was to determine the effects of poor maternal nutrition during gestation on the oxidative status in offspring skeletal muscle in sheep. We hypothesized that offspring of restricted- and over-fed ewes would have decreased antioxidant activity and increased products of oxidative stress in skeletal muscle. To test this hypothesis, multiparous Dorset ewes (n = 46) pregnant with twins were fed 100% (CON), 60% (RES), or 140% (OVER) of total nutrient requirements (NRC) from d 30 of gestation until parturition. Following parturition, ewes were fed a control diet throughout lactation. At d 282 of age semitendinosus (STN) samples were collected from rams at necropsy, and at d 284 of age muscle biopsies from STN were collected from ewes. Data were analyzed in SAS using PROC MIXED with fixed effects of maternal diet and offspring sex. Data were considered significant at P ≤ 0.05. The activity of the endogenous antioxidant superoxide dismutase (SOD) was decreased by 45% and 33% in RES and OVER offspring, respectively, compared with CON (P ≤ 0.01). Offspring sex did not alter STN SOD activity (P = 0.35). Muscle glutathione peroxidase (GPx) activity was decreased in RES offspring by 20% compared with CON (P ≤ 0.04), but neither differed from OVER offspring (P ≥ 0.24). Ewes had 34% greater GPx activity compared with rams (P &amp;lt; 0.0001). Offspring from RES and OVER ewes had 77% and 87% greater concentrations of malondialdehyde (MDA), a marker of lipid peroxidation, when compared with CON (P &amp;lt; 0.0001). Ewes had 29% greater MDA concentrations compared with rams (P = 0.05). Protein carbonyl (PC), a marker of protein oxidation, concentrations were 36% and 38% greater in RES and OVER offspring, respectively, compared with CON (P ≤ 0.01). The decrease in antioxidant activities and increase in products of protein and lipid oxidation in offspring from poorly nourished dams suggests dysregulation in skeletal muscle oxidative status that may contribute to the negative consequences observed in offspring. Future work should focus on determining the mechanistic role of skeletal muscle oxidative stress in the decreased quantity and quality of animal protein products and identifying potential strategies to mitigate alterations in oxidative status as a result of poor maternal nutrition during gestation.

282 Effects of granddam poor maternal nutrition during gestation on second generation offspring oxidative status in circulation and skeletal muscle

Abstract Poor maternal nutrition (under- or over-feeding) during gestation negatively impacts antioxidant activity and oxidative stress markers in first generation (F1) offspring. To determine if these alterations persist into subsequent generations, multiparous Dorset ewes (F0; n = 46) pregnant with twins were fed 100% (CON), 60% (RES), or 140% (OVER) of total nutrient requirements (NRC) from d 30 of gestation until parturition. At 16 to 19 mo of age, F1 ewes (n = 37) were maintained on a control diet and bred to generate second generation offspring (F2; CON-F2, RES-F2, OVER-F2 corresponding to F0 diet). At 112 and 224 d of age, plasma samples were collected from F2 offspring, and at d 284 semitendinosus (STN) samples were collected from rams at necropsy and muscle biopsies in ewes. Data were analyzed in SAS using PROC MIXED where significance was determined at P ≤ 0.05. Circulating superoxide dismutase (SOD) activity was decreased by 21% and 25% in RES-F2 and OVER-F2 offspring, respectively, compared with CON-F2 (P &amp;lt; 0.0001). Plasma SOD activity was 17% less at d 224 than d 112 (P &amp;lt; 0.0001). Ewes had 9% greater circulating SOD activity compared with rams (P = 0.03). Muscle SOD activity was 31% and 35% greater in CON-F2 compared with RES-F2 and OVER-F2 offspring, respectively (P ≤ 0.003). Rams had 26% greater STN SOD activity than ewes (P = 0.006). Plasma glutathione peroxidase (GPx) activity was 14% greater in CON-F2 than RES-F2 and OVER-F2 offspring (P ≤ 0.003). Circulating GPx activity was 14% less at d 224 than d 112 (P &amp;lt; 0.0001). Muscle GPx activity was 39% and 35% greater in CON-F2 offspring compared with RES-F2 and OVER-F2, respectively (P &amp;lt; 0.0001). Ewes had 11% and 16% greater GPx activity in circulation and STN, respectively, than rams (P ≤ 0.005). Plasma concentrations of malondialdehyde (MDA) were 18% and 10% greater in RES-F2 and OVER-F2 offspring, respectively, than CON-F2 (P = 0.004). Circulating MDA concentrations were 20% greater at d 224 compared with d 112 (P &amp;lt; 0.0001). Concentrations of MDA in STN were increased in RES-F2 and OVER-F2 offspring by 36% and 50%, respectively, compared with CON-F2 (P ≤ 0.006). Ewes had 87% greater concentrations of MDA in STN compared with rams (P &amp;lt; 0.0001). Circulating protein carbonyl (PC) concentrations were 16% greater in RES-F2 offspring than CON-F2 and OVER-F2 (P ≤ 0.04). Plasma PC concentrations were 9% greater at d 224 compared with d 112 (P = 0.04). The concentrations of PC in STN were 81% and 69% greater in RES-F2 and OVER-F2 rams, respectively, compared with CON-F2 rams (P ≤ 0.0001). Alterations in oxidative status persist into the F2 generation and may impact muscle growth and metabolism.

Long-term effect of inbreeding in the yellow steppe lemming, Eolagurus luteus, captive colony

Abstract In the current research, we investigated the impact of gradually increasing inbreeding on the life span and reproductive rate of yellow steppe lemmings, Eolagurus luteus, that reproduced in the Moscow Zoo. The focal captive colony existed from 2017 to 2021. The studied animals belonged to the second to tenth generations. The founders of the colony were 5 females and 5 males originating from 3 females and 4 males livetrapped in the Zaisan basin (Kazakhstan). The degree of their descendant relatedness progressively increased. The animals intended to be used for reproduction were distributed to pairs with unfamiliar partners. We constructed the pedigree of 177 individuals and calculated their inbreeding coefficients. This parameter varied from 0 to 0.29, and the maximum values were registered in the lemmings of the seventh to tenth generations. We measured the life span of 61 individuals and used information about the reproduction or its absence in 45 pairs. A substantial decline in individual life span and reproductive parameters in the breeding pairs, along with a progressive increase in the inbreeding coefficients, was registered. The number of delivered litters, born pups, and young lived up to the age of puberty significantly depended on the level of mother inbreeding. The noticeable traits of inbreeding depression in the colony appeared in 2019–2020 when the offspring inbreeding coefficients reached approximately 0.2. Therefore, we assume that if the E. luteus population originates from a relatively small number of noninbred and unfamiliar individuals, then successful reproduction without significant inbreeding depression will continue for several generations of offspring.

Paternal zinc deficiency alters offspring metabolic status in Drosophila melanogaster

BackgroundThis study delves into the understudied yet potentially crucial role of paternal zinc deficiency in programming offspring metabolic outcomes. By examining paternal zinc deficiency, we aim to shed light on a previously unexplored avenue with the potential to significantly impact future generations. We investigated the intergenerational effects of paternal zinc deficiency on metabolic parameters in Drosophila melanogaster. MethodsDietary zinc deficiency was induced by supplementing the diet of Drosophila F0 male flies with TPEN (N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine) from egg stage. The F0 male flies after eclosion were mated with age-matched virgin female flies from the control group, resulting in the F1 offspring generation. The F1 generation were then cultured on a standard diet for subsequent metabolic analyses, including assessments of body weight, locomotion, and levels of glucose, trehalose, glycogen, and triglycerides as well as the expression of related genes. ResultsWe observed an increase (p<0.05) in body weight in male parent flies and female offspring. Negative geotaxis performance was also impaired in the female offspring. Paternal zinc deficiency exerted distinct effects on carbohydrate and lipid metabolism, as evidenced by a significant (p<0.05) increase in trehalose and triglyceride levels in both parent and offspring. Additionally, zinc deficiency led to alterations in the expression of key metabolic genes, including significant (p<0.05) increase in DILP2 mRNA levels, highlighting potential links to insulin signaling. Also, there were reduced mRNA levels of SOD1 and CAT in both parental and offspring generations. Parental zinc deficiency also increased the expression of Eiger and UPD2 mRNA in the offspring, suggesting potential perturbations in the immune response system. ConclusionThese findings underscore the link between zinc status and various physiological and molecular processes, revealing both immediate and intergenerational impacts on metabolic, antioxidant, and inflammatory pathways and providing valuable insights on the implications of paternal zinc deficiency in Drosophila melanogaster.

Second generation lethality in RNAseH2a knockout zebrafish.

Removal of ribonucleotides from DNA by RNaseH2 is essential for genome stability, and its impacted function causes the neurodegenerative disease, Aicardi Goutières Syndrome. We have created a zebrafish rnaseh2a mutant to model this process. Surprisingly, RNaseH2a knockouts show little phenotypic abnormality at adulthood in the first generation, unlike mouse knockout models, which are early embryonic lethal. However, the second generation offspring show reduced development, increased ribonucleotide incorporation and upregulation of key inflammatory markers, resulting in both maternal and paternal embryonic lethality. Thus, neither fathers or mothers can generate viable offspring even when crossed to wild-type partners. Despite their survival, rnaseh2a-/- adults show an accumulation of ribonucleotides in both the brain and testes that is not present in early development. Our data suggest that homozygotes possess RNaseH2 independent compensatory mechanisms that are inactive or overwhelmed by the inherited ribonucleotides in their offspring, or that zebrafish have a yet unknown tolerance mechanism. Additionally, we identify ribodysgenesis, the rapid removal of rNMPs and subsequently lethal fragmentation of DNA as responsible for maternal and paternal embryonic lethality.

Generation of rat offspring from ovarian oocytes by xenotransplantation

The idea of utilizing unused oocytes present in the ovaries has been tested in various ways to produce offspring. However, only a limited number of studies succeeded in offspring generation. They include transplantation of ovaries into autologous or allogeneic animals, and acquisition of pups from oocytes obtained by transplanting mouse ovaries into immunodeficient rats. Here we report successful production of rat oocytes by transplanting rat ovaries under the kidney capsule of immunodeficient mice with addition of hormone administration to the mice. In addition, these oocytes were developed by in vitro fertilization, and transplanted into the oviducts of pseudopregnant rats, resulting in successful delivery of pups. The modified gene of the donor rat was confirmed to be correctly inherited to the pups. These results show that xenotransplantation of ovarian tissue makes it possible to leave offspring, beginning a new phase in developmental engineering.

A constrained multi-objective evolutionary algorithm based on fitness landscape indicator

Constrained multi-objective optimization problems (CMOPs) with constraints in both the decision and objective space are shown to be great challenges to be solved. Considering the different requirements of different problems on resource allocation of exploration and exploitation, this paper proposes a new constrained multi-objective evolutionary algorithm based on a novel fitness landscape indicator. The indicator regards the fitness landscape and evolutionary generation among the population to determine the selection of the offspring generation mechanism. The proposed algorithm uses the new indicator to select different differential evolutions during the evolutionary process to balance exploration and exploitation. Numerical experiments on three test suites and three practical examples compared with six existing algorithms show the proposed algorithm can effectively deal with different types of CMOPs, especially in CMOPs with constraints in both the decision and objective spaces.

Psychological health among adult offspring of lesbian parents at a time of anti-LGBTQ+ oppression

ABSTRACT This study investigates potential differences in psychological health (i.e. life satisfaction, anticipated future life satisfaction, distress), social well-being, and experiences of victimisation among adult offspring born to lesbian parents when compared with participants from a nationally representative sample surveyed in the same historical context of renewed anti-LGBTQ+ oppression. The research involved 75 adult offspring (M = 30.93, SD = 0.93; sex assigned at birth: 39 female and 36 male; gender identity: 73 cisgender and 2 gender nonbinary; sexual orientation: 51 heterosexual and 24 sexual minority) of the first generation conceived through donor insemination by lesbian parents. These offspring were matched with 75 participants of a U.S. probability sample based on several factors, including age, race/ethnicity, education, sex assigned at birth, gender identity, and sexual orientation. The comparison group is presumed to have been raised by heterosexual parents. After applying Bonferroni’s correction to minimise the risk of Type I errors resulting from multiple comparisons, no significant differences emerged in the study variables between the two samples. Despite a climate of renewed anti-LGBTQ+ oppression, adult offspring of lesbian parents were doing well, possibly due to unique socialisation processes in childhood when their parents taught them to be resilient even in the face of socio-environmental challenges.

Cadmium Exposure in Male Rats Results in Ovarian Granulosa Cell Apoptosis in Female Offspring and Paternal Genetic Effects.

The aim of this study was to investigate whether the damage to male offspring induced by cadmium (Cd) exposure during embryonic period leads to the apoptosis of ovarian granulosa cells (OGCs) in the next generation of female offspring, and whether this apoptosis in the offspring was due to paternal genetic effects. Pregnant Sprague-Dawley (SD) rats were exposed to CdCl2 (0, 0.5, 2.0, or 8.0 mg/kg) by gavage daily for 20 days to produce the filial 1 (F1) generation. F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was generated in the same way. No apoptotic bodies were observed in the OGCs of either the F2 or F3 generation as shown by electron microscopy, and a reduced OGC apoptosis rate (detected by flow cytometry) was observed in F2 OGCs from the Cd-exposed group. Moreover, the mRNA (qRT-PCR) levels of Bax and Bcl-2 and the protein (western blotting) level of pro-caspase-8 increased in the F2 generation (p < 0.05). The expression of apoptosis-related miRNAs (qRT-PCR) and methylation of apoptosis-related genes (determined via bisulfite-sequencing PCR) in OGCs were further determined. Compared with those of the controls, the expression patterns of microRNAs (miRNAs) in the F2 offspring were different in the Cd-exposed group. The miR-92a-2-5p expression levels were decreased in both the F2 and F3 generations (p < 0.05), while the average methylation level of apoptosis-related genes did not change significantly (except for individual loci). In summary, this study showed that the paternal genetic intergenerational effect of male Cd exposure during embryonic period induced apoptosis of OGCs in the offspring was weakened, and the transgenerational effect disappeared; nevertheless, intergenerational and transgenerational changes in apoptosis-related genes, epigenetic modifications, DNA methylation, and miRNAs were observed, and may be important for understanding the homeostatic mechanisms of the body to alleviate the intergenerational transmission of Cd-induced damage.

Adult Offspring of Deer Mouse Breeding Pairs Selected for Normal and Compulsive-Like Large Nesting Expression Invariably Show the Same Behavior Without Prior In-Breeding.

Obsessive-compulsive disorder is a neuropsychiatric condition with notable genetic involvement. Against this background, laboratory-housed deer mice of both sexes varyingly present with excessive and persistent large nesting behavior (LNB), which has been validated for its resemblance of clinical compulsivity. Although LNB differs from normal nesting behavior (NNB) on both a biological and cognitive level, it is unknown to what extent the expression of LNB and NNB is related to familial background. Here, we randomly selected 14 NNB- and 14 LNB-expressing mice (equally distributed between sexes) to constitute 7 breeding pairs of each phenotype. Pairs were allowed to breed two successive generations of offspring, which were raised until adulthood (12 weeks) and assessed for nesting expression. Remarkably, our findings show that offspring from LNB-expressing pairs build significantly larger nests compared to offspring from NNB-expressing pairs and the nesting expression of the offspring of each breeding pair, irrespective of parental phenotype or litter, is family specific. Collectively, the results of this investigation indicate that LNB can be explored for its potential to shed light on heritable neurocognitive mechanisms that may underlie the expression of specific persistent behavioral phenotypes.