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Weathering the storm: Most maternal and environmental drivers of individual reproductive success do not scale up to population recruitment in a large herbivore.

Population growth depends upon individual survival and reproduction, but do drivers of individual reproductive success scale up to population recruitment? Factors affecting individuals may have little effect on population dynamics if individuals within a population experience different conditions. When seasonal resource availability is unpredictable and breeding season long, average conditions over a breeding cycle may poorly reflect the environment experienced by many individuals. We compared the drivers of individual reproductive success and population recruitment in an asynchronously breeding large herbivore, the eastern grey kangaroo (Macropus giganteus). We analysed 18 years of individual-based data using multivariate hierarchical Bayesian models to first identify the causal mechanisms relating population density, environmental conditions and maternal traits to individual success. We then assessed whether the drivers of individual reproductive success scaled up to determine population recruitment. Most maternal and environmental covariates strongly influenced individual reproductive success, with distinct effects on juvenile survival before and after pouch exit. Maternal traits had a greater influence in the pouch, whereas environmental conditions became increasingly important once young exited the pouch. Most drivers of individual reproductive success did not affect population recruitment. Recruitment increased with population density and mean body condition of adult females. Weather harshness had a weak positive effect on recruitment, which appeared independent of female age structure, previous recruitment or forage. Most drivers of individual reproductive success did not scale up to population recruitment. Birth asynchrony could buffer population recruitment against environmental variation such that variables affecting individual reproduction have little impact at the population level. Large herbivores that reproduce asynchronously may therefore be more resilient to environmental variability than synchronous breeders.

Bayesian modelling

The inheritance of growth and form in the mouse. IV. Changes in the variance components of weight, tail length and tail width during growth.

A complete diallel cross, including inbreds and reciprocals, was made among six inbred lines of mice. Body weight, tail length and tail width were measured at ages of 1 through 12 weeks. The analysis described by Griffing (1956a, 1956b, 1958) as the modified diallel, method 3, model II was made for each trait at each age, a separate analysis being made for each sex. Inbreds did not contribute to estimates of the effects in the diallel model, but were used to estimate heterosis. Positive heterosis was observed for all three traits. Heritability increased with age for all three traits, although it remained small for tail width; for body weight it was larger in females than for males, while for tail length and width the opposite was true. Non-additive genetic variance was observed for all three traits. Maternal effects variance was virtually non-existent for tail length, but for body weight and tail width exhibited a marked peak around weaning, followed by a gradual decline for body weight and a rapid decline for tail width. Environmental variance exhibited a marked peak at weaning for all three traits and was larger for male body weight and tail length from four weeks onward. Residual reciprocal effects were important for tail length at all ages, but were small or negligible for body weight and tail width. It is concluded that the relative importance of the individual's genotype in determining size increases with age, while that of non-genetic factors declines.

Age Factors

Effect of environmental factors and fetal and maternal genotype on gestation length and birth weight of Holstein calves.

Records of gestation length and birth weight on 1522 live single births (from 1958 to 1976) of Holstein calves were from 81 sires and 552 dams. Average gestation length was 282.3 days, and average birth weight was 42.9 kg. Male calves were carried 1.7 days longer than female calves and weighed 2.9 kg more at birth. Both gestation length and birth weight increased with parity. Calves born in spring and summer were carried shorter times and weighed less than those born in fall and winter. Heritabilities of gestation length and birth weight as progeny traits were .73 and .51 and as maternal traits were .19 and .26. Genetic correlations between gestation length and birth weight were .46 as a progeny trait and .35 as a maternal trait. Genetic correlations between progeny traits and maternal traits were negative. The phenotypic correlation between gestation length and birth weight was .37, and environmental correlation was .30.

Animals

A further assessment of predictors of the child's behavior in dental treatment.

The child's disruptiveness during dental treatment was related modestly to his age as well as his state, trait, and dental anxiety. In three samples comprising 132 experienced and 49 inexperienced pedodontic patients, the child's behavior during treatment could not be predicted from any aspect of maternal anxiety -- trait, state, or dental. Previous conceptions of maternal influence on the child's dental anxiety should be re-evaluated.

Anxiety

Genomic early growth mechanisms of two endangered Mexican spruces.

This study elucidated the genomic basis of family-level growth variance in the critically endangered endemic Mexican spruces Picea martinezii and P. mexicana by: (i) analyzing family- and population-level variations in seedling basal diameter and height after 12 months of growth under common garden conditions and seed weight as maternal provisioning trait; and (ii) identifying genomic loci (SNPs) associated with these traits. Despite limited sample sizes (77 and 74 families representing all known populations of both species), 32 and 10 outlier SNPs were identified yielding 17 and six annotated candidate genes in P. martinezii and P. mexicana, respectively. These genes showed contrasting multivariate associations suggesting species-specific hypothesized growth strategies at the family level: defense-oriented framework in P. martinezii and plasticity-driven response in P. mexicana. Notably, several candidate genes encode key components of growth hormone pathways, including a gibberellin-regulated protein, a cytokinin hydroxylase and the AP2-like transcription factor ANT, providing valuable insights into how maternal genetic variation corresponds to the hormonal pathways that govern cell proliferation and organ size in the progeny. Integration of these findings with the contrasting demographic histories of both species revealed that population bottlenecks enhance the detectability of growth-associated variants by reducing background genetic variation. These genomic resources provide actionable information for prioritizing conservation measures, implementing assisted gene flow to maintain adaptive potential under climate change and designing future breeding programs. With 80.9-99.6% sequence identity to conserved Picea abies homologs, these findings may extend across the genus.

Picea

Teratocarcinoma cells as vehicles for introducing specific mutant mitochondrial genes into mice.

The immediate purpose of the experiment was to establish a means of introducing specific mitochondrially encoded mutant genes into mice. Mouse teratocarcinoma stem cells were used as vehicles for the cytoplasmic markers because of their known capacity for normal somatic and germinal differentiation after injection into blastocysts. The mutation of choice, chloramphenicol resistance (CAP(R)), was first produced in a melanoma cell line by mutagenesis and selection. The CAP(R) trait was then transferred from a resistant melanoma cell to a sensitive (CAP(S)) teratocarcinoma cell by fusing to the latter only the cytoplasmic portion of the CAP(R) donor. This indirect route demonstrated the cytoplasmic provenance of the mutation. Protein synthesis in mitochondria isolated from the cybrid, or cytoplasmic hybrid, cells was barely affected by chloramphenicol, in contrast to the inhibitory influence of the drug on mitochondria of the parent teratocarcinoma line. Cells of the cybrid clone resembled teratocarcinoma cells and retained their ability to form diverse tissues in solid tumors produced from subcutaneous grafts. Cells from the tumors were retransplanted and were tested periodically by culture in chloramphenicol; they were found to be stably CAP(R) even after 16 weeks in vivo in the absence of the selective agent. The CAP(R) cybrids were microinjected into blastocysts of another inbred strain and, after transfer to foster mothers, mosaic mice were obtained. They comprised both cybrid- and blastocyst-derived cells in various tissues, as indicated by strain-specific nuclear markers. These results demonstrate successful normal differentiation of the CAP(R) lineage in vivo. Teratocarcinoma cybrids thus offer a practical portal of entry of preselected mitochondrial genes into mice. This will ultimately permit in vivo investigation of maternally transmitted traits, of mitochondrial genetic influences in specialized cells, and of possible roles of cytoplasmic genes in clinical and disease states.

Animals

Genetic analysis of lines selected for wing vibration in Drosophila melanogaster.

Selection for the wing vibration component of courtship in the Oregon-R stock of D. melanogaster was practiced for 44 generations. Selection was successful, indicating that there is genetic variation for the trait in the Oregon-R stock. The mean realized heritability of the trait, based on the first 11 generations of selection, was 15%. Biometrical analysis showed that there is some additive genetic variance for the trait with the possibility of some ambidirectional dominance. No maternal effects for the trait were found.

Animals

Genetic analysis of nurse dams selected for six-week body weight or postweaning gain in mice.

A modified crossfostering technique was developed to compare the performance of nurse dams in selected and control populations of mice. The H6 and M16 populations were selected for increased 6-week body weight and 3- to 6-week postweaning gain, respectively, while the C2 and ICR populations were the respective controls. Crossfostering was performed using H6, M16 and their reciprocal F1 crosses as nurse dams in the selected crossfostering group and C2 ICR and their reciprocals in the control group. Measurements recorded for nurse dams included mean body weight of 8 young within a nursed litter at birth (MWB) and 12 days of age (MW12). The latter was used as a measure of postnatal maternal performance. Other traits recorded for nurse dams were number born (NB), body weight at parturition (DWP) and 12 days postpartum (DW12), and weight gain (DWG), feed intake (FED) and efficiency (EFF = DWG/FED) for the first 12 days of lactation. The correlated response in MW12 was negative (P less than .01) for M16 and essentially zero for H6. Both lines exhibited positive (P less than .01) correlated responses in DWP and DW12 and no change in EFF. Only the H6 line increases significantly in DWG and FED as a result of selection. NB increased in M16 and H6, but was significant for the latter population only. Population differences in selection response [(M16-ICR)-(H6-C2)] were significant for FED only, primarily due to average direct genetic effects. Direct comparisons of M16 and H6 indicated that M16 was larger in DWP and DW12 but smaller in DWG and EFF. Average direct genetic effects favored M16 for NB, DWP, and DW12, whereas average maternal genetic effects favored H6 for NB, DWP, DW12 and FED. Percent direct heterosis, in F1 crosses of selected populations was significant for MW12 (13.7%) ,FED (10.8%) and NB (11.4%). Direct heterosis in F1 crosses of the controls was significant for MW12 (9.4%), NB (6.6%), DWP (3.5%), DW12 (3.3%) and FED (4.4%). The effects of MW12, DWG and metabolic body size (MBS) accounted for 47% of the variation in FED, pooled within populations. Of these variables, MW12 accounted for the highest proportion (32%) of variation in total feed intake.

Animals

Maternal and fetal outcome associated with hemoglobin E trait and hemoglobin E disease.

A study of 20 patients with hemoglobin E trait abnormality and 8 patients with hemoglobin E disease in pregnancy is presented. The hematologic abnormality in HbE hemoglobinopathy is mild though hemoglobin values are significantly lower than in HbA patients. Fetal wastage is no increased and the salvage rate is high (live births over 95 per cent). The mean birthweight of the baby in HbE patients is significantly lower than in HbA patients, but the incidence of prematurity is not significantly increased in HbE patients. Blood loss at delivery is not markedly affected by hemoglobin type. The incidences of postpartum hemorrhage, preeclampsia, and malaria are not significantly increased in HbE patients; the reason for the significant increase in incidence of abruptio placentae in HbE is not known. No maternal deaths or congenital fetal abnormalities were recorded. It is concluded that the course of pregnancy in HbE trait abnormality and HbE disease is relatively benign.

Abortion, Spontaneous

Amniocentesis in the early second trimester of pregnancy and maternal anxiety.

Anxiety state and trait were measured before and after amniocentesis early in the second trimester of pregnancy, in a group of 28 women who were at risk of bearing an abnormal foetus. A significant decrease in maternal anxiety occurred in the majority of women after receiving the results of the amniocentesis. It is concluded that amniocentesis for intrauterine diagnosis of foetal abnormalities makes a significant contribution to the psychological wellbeing of those pregnant women who are at greater risk of having an abnormal baby.

Adult

Scaling linear-model breeding values to the liability scale: an application to pig binary traits.

In commercial pig production, many important traits are recorded as binary phenotypes. For such traits, threshold models offer an appropriate framework but are computationally intensive. Thus, linear models are widely used to obtain genomic estimated breeding values (GEBV); however, these are on the observed scale (phenotypic). This creates the need for a robust method to approximate GEBV from linear models to the liability scale. A recently proposed approximation showed good concordance for low-prevalence traits (<5%) but has not yet been tested for a wider range of prevalence values and for models with more than one random effect. We aimed to evaluate the performance of this approximation for pig binary traits with prevalences ranging from <5% to >86%, in both animal and maternal animal models. Data were available for five fitness traits (FT1-FT5), with up to 233k animals with phenotypes, of which 204k animals were genotyped with a 25k SNP array. Variance component estimates were obtained using threshold models. Classical animal models were used for FT1-FT3, and maternal animal models for FT4 and FT5. Variance components on the observed scale were then obtained by multiplying estimates from a threshold model by the square of the height of the standard normal density evaluated at the threshold. GEBV were predicted using single-step genomic best linear unbiased prediction under both linear and threshold models. The approximation tested involved scaling the GEBV using the height of the ordinate of the standard normal distribution evaluated at the threshold as a scaling factor. The agreement between GEBV from the scaled linear model and the threshold model on the probability scale was evaluated using Pearson and Spearman correlations, mean squared error (MSE), regression parameters, overlapping coefficient (OVL), distribution overlap, and classification accuracy (CACC). Correlations between linear and threshold GEBV ranged from 0.94 (low-prevalence traits) to 0.99 (high-prevalence traits) for the direct GEBV and were 0.99 for the maternal GEBV. MSE were close to zero. The OVL exceeded 0.83 for all traits. CACC ranged from 95.10% to 98.33% for the direct GEBV and from 92.54% to 97.42% for the maternal GEBV. Regardless of model and trait prevalence, this approximation yielded GEBV that are highly consistent with threshold model GEBV, providing a reliable, practical approach for large-scale pig genetic evaluations for binary traits using linear models.

Animals

Aggregation of coronary risk factors in families of men with fatal and non-fatal coronary heart disease.

The occurrence of main coronary risk factors was assessed in the families of 211 men under age 56 from East Finland. Fifty men were survivors of a recent myocardial infarction, 55 had died of myocardial infarction, 53 suffered from uncomplicated angina, and 53 were healthy reference men. Familial hyperlipidaemia was twice and familial hypertension three times as common in case as in reference families; other risk factors were equally common in both. Familial hypercholesterolaemia was commonest in the families of men with fatal myocardial infarction, and multiple type familial hyperlipidaemia in those of men with angina. Any increase in familial aggregation of coronary heart disease was invariably paralleled by increased aggregation of hyperlipidaemia and hypertension, with the most impressive aggregation of both traits in case families with a maternal history of early coronary death. It is concluded that most of the familial aggregation of coronary heart disease is mediated by familial aggregations of hyperlipidaemia and hypertension.

Adolescent

Abnormal haemoglobins in the Sudan savanna of Nigeria. II. Immunological response to malaria in normals and subjects with sickle cell trait.

Children born in areas hyperendemic for Plasmodium falciparum are protected by maternal antibodies for up to about five months of life, after which they are subject to intense infection until they acquire sufficient immunity--by about five years of age. Children with sickle cell trait (Hb.AS) are at an advantage during these critical years, probably because of preferential phagocytosis of parasitized red cells. This could lead to either (i) early processing of antigen by macrophages and an accelerated immune response, or (ii) less antigenic stimulus and hence lower antibody production. Immunoglobulin (Ig)G and IgM determinations, agar gel diffusion (Ouchterlony) against soluble P. falciparum antigen, the indirect fluorescent antibody (IFA) test using P. falciparum and P. malariae antigens, and the indirect haemagglutination (IHA) test with P. falciparum antigen were performed on sera from a population with different Hb electrophoretic types in the hyperendemic malarial area of Garki, Kano State, Nigeria. Plasma immunoglobulins and antimalarial antibodies rose with age. After the first year of life, lower mean concentrations of immunoglobulins (especially IgM), and lower mean titres of antibodies specific against P. falciparum (Ouchterlony, IHA and less significantly IFA) were present in Hb.AS compared to Hb.AA; these differences increased with age. Antimalarial intervention was followed by a decline of all values and final levels showed little difference between haemoglobin types. It was unlikely that either a relative inability to produce antibody or a more rapid catabolism of immunoglobulins was responsible for the lower levels in sickle cell trait. The observations are more easily explained by the hypothesis that Hb.AS persons have less antigenic stimulus due to the early removal of parasitized sickled cells by macrophages, which then degrade the antigens. The antibody difference between Hb.AA and Hb.AS increased throughout life, suggesting that this process remained a feature of sickle cell trait even after parasite frequencies and densities were similar in the two Hb groups. These observations have implications in the aetiology of tropical splenomegaly syndrome, which is rarely seen in sickle cell trait subjects. Mean IgG and IgM were slightly higher in Hb.AS than Hb.AA infants, the difference for IgG achieving significance. This suggested that during infancy early phagocytosis of parasitized cells had led to enhanced processing of antigen and hence an earlier immune response in Hb.AS, but this was unlikely to be a major factor in survival. IFA titres against P. malariae were slightly but not significantly lower in Hb.AS, possibly as a result of cross-reaction with P. falciparum antibody or of a slight degree of protection against P. malariae.

Adolescent

Prader-Willi syndrome as a neurogenetic model for psychosis and obsessive-compulsive disorder: A review of clinical, behavioral, and biological insights.

Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder classically defined by hyperphagia and obesity. However, its profound psychiatric phenotype offers a unique genetic framework for understanding major mental illnesses. This review positions PWS as a potentially informative biological model for psychosis and obsessive-compulsive disorder (OCD), bridging the gap between 15q11-q13 imprinting defects and neural circuit dysfunction. We synthesize evidence demonstrating that psychosis in PWS is not a uniform trait but is disproportionately linked to the maternal uniparental disomy (mUPD) subtype. This genotype-phenotype correlation suggests that overexpression of maternally imprinted genes and loss of paternal expression disrupt cortical excitatory-inhibitory balance, resembling the "schizophrenia-bipolar" genomic architecture. Furthermore, synthesized evidence characterizes the repetitive, ritualistic behaviors in PWS not merely as behavioral challenges, but as a developmentally arrested OCD-spectrum phenotype driven by distinct serotonergic-oxytocinergic imbalances and hypothalamic-limbic dysconnectivity. Mechanistic insights from preclinical models of MAGEL2, SNORD116, and NDN deficiency are integrated with clinical findings to highlight shared neurobiological substrates. Finally, we outline a roadmap for precision psychiatry in PWS, emphasizing the necessity of pharmacogenomics in antipsychotic management and the potential of targeted circuit-based therapeutics. By deconstructing the psychiatric comorbidities of PWS, we provide a framework for translating genomic architecture into mechanistic understanding and targeted treatment for complex neuropsychiatric disorders.

15q11-q13

The heterogeneity of rat-liver mitochondrial DNA.

Two types of mitochondrial DNA (mtDNA) can be distinquished in an inbred strain of rats of the Wistar type. The population of DNA molecules of the liver of one single rat is homogeneous. This was shown for a number of 100 animals and confirms the data of other investigators. The two types of mitochondrial DNA, designated A and B, differ in their number of cleavage sites for the restriction endonucleases Eco RI (2sites), Hind II (1 site) and Hha I (1 site). No differences were found for the restriction enzymes Bam HI, Hap II, Hind III and Hpa I. The degree of sequence divergence of the two types of DNA is calculated to be roughly 5% on the basis of these observations. From 20 rats part of the liver was taken and the mtDNA was characterized. Heterologous and homologous crosses between type A and type B rats were made. Analysis of the offspring revealed strictly maternal inheritance of the A and B mtDNA traits. For purposes of base-sequence analysis and RNA.DNA hybridization the strain could easily be "purified" genetically.

Animals

Influence of Gonadal and Chromosomal Sex on the Brain Transcriptome in a Mouse Species with Natural Sex Reversal.

Sex chromosomes are expected to play a role in shaping the transcriptional architecture of sexual dimorphism, through the direct expression of sex-linked genes, by regulating autosomal genes, or in interactions with hormones. Yet, their degree of involvement remains elusive partly because chromosomal sex (e.g. XX/XY) and gonadal sex (ovaries or testes) are usually inextricably intertwined. They are, however, dissociated in the African pygmy mouse, Mus minutoides, in which a feminizing X (X*) has evolved, resulting in three female genotypes (XX, XX*, and X*Y) and one male genotype (XY). Furthermore, all sex chromosomes are fused to autosomes (neo-sex chromosomes: neo-X, neo-X* and neo-Y). Despite complete sex reversal, X*Y females show distinctive phenotypes with greater fertility, divergent maternal care strategies, and the masculinization of some traits (e.g. enhanced aggressiveness). By comparing the brain transcriptome of the four sexual genotypes, we show that differential gene expression is mainly linked to gonadal sex but also, and significantly, to chromosomal sex. Genes influenced by chromosomal sex are overrepresented on sex-linked genomic regions, and some are strong candidates to explain X*Y-specific behavioral and reproductive traits. Our results also suggest the preferential inactivation of the X* chromosome in XX* females, only in the brain, which could explain their trait similarities with XX females. Overall, we show that sex and neo-sex chromosomes have profoundly impacted the brain transcriptome in ways that reflect their new transmission modes, evolutionary trajectories, and resulting genomic conflicts.

Animals

Congenital perceptive hearing loss and atopic dermatitis.

Two brothers were suffering from perceptive hearing loss, atopic dermatitis and mild palmophantar keratoderma. There was a predisposition to atopic disease in the maternal family, and palmoplantar keratosis as a dominant trait in the paternal family. Atopoc dermatitis and palmoplantar keratoderma separately have been reported to co-exist with hearing loss, but a combination of all three has not so far been reported.

Adolescent