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In this article, I review the literature to determine how successful the latent trait theory model of personality from differential psychology has been for studying personality in non-human primates. The evidence for the success of this model is quite good, and offers insights and directions for personality research in primates and other animals. This, I conclude, stems from (i) the human trait model's simplicity, and (ii) the fact that the human differential model of personality developed in the face of harsh criticism, which led researchers to test and refine their models.

This study investigated the impact of overexpressing the mitochondrial enzyme Fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) in human osteosarcoma epithelial cells (U2OS) in vitro. While the downregulation or knockdown of FAHD1 has been extensively researched in various cell types, this study aimed to pioneer the exploration of how increased catalytic activity of human FAHD1 isoform 1 (hFAHD1.1) affects human cell metabolism. Our hypothesis posited that elevation in FAHD1 activity would lead to depletion of mitochondrial oxaloacetate levels. This depletion could potentially result in a decrease in the flux of the tricarboxylic acid (TCA) cycle, thereby accompanied by reduced ROS production. In addition to hFAHD1.1 overexpression, stable U2OS cell lines were established overexpressing a catalytically enhanced variant (T192S) and a loss-of-function variant (K123A) of hFAHD1. It is noteworthy that homologs of the T192S variant are present in animals exhibiting increased resistance to oxidative stress and cancer. Our findings demonstrate that heightened activity of the mitochondrial enzyme FAHD1 decreases cellular ROS levels in U2OS cells. However, these results also prompt a series of intriguing questions regarding the potential role of FAHD1 in mitochondrial metabolism and cellular development.

FAHD1 is a mitochondrial enzyme involved in oxaloacetate metabolism, with emerging links to cellular redox balance, Ca 2+ -metabolism, and structural features. Building on previous work (Heberle et al. Sci Rep 14:9231, 2024), we investigated how overexpression of human FAHD1 (hFAHD1) variants, including wild-type, the catalytically inactive hFAHD1-K123A, and the hyperactive hFAHD1-T192S, affects nuclear morphology in U2OS osteosarcoma cells. Using high-content microscopy and automated classification, we observed variant-specific shifts in nuclear shape distributions. Notably, expression of K123A was associated with a higher frequency of large, rounded nuclei and a reduction in elongated forms, while the T192S variant produced subtler changes. By aligning morphological clusters with available proteomic profiles, we identified suggestive correlations with differences in biosynthetic activity and chromatin organization. These findings indicate that altered FAHD1 activity is correlated with changes in nuclear morphology and may be associated with broader cellular organization. Our results are descriptive and hypothesis-generating, highlighting possible links between mitochondrial metabolic states and nuclear architecture that warrant further validation.

Metallothioneins (MTs) are a family of mostly low-molecular weight, cysteine-rich proteins capable of specific metal-ion binding that are involved in metal detoxification and homeostasis, as well as in stress response. In contrast to most other animal species which possess two-domain (bidominial) MTs, some gastropod species have evolved Cd 2+ -selective multidomain MTs (md-MTs) consisting of several concatenated β3 domains and a single C-terminal β1 domain. Each domain contains three-metal ion clusters and binds three metal ions. The terrestrial snail Alinda biplicata possesses, among other MT isoforms, an md-MT with nine β3 domains and a C-terminal β1 domain (termed 10md-MT), capable of binding up to 30 Cd 2+ ions per protein molecule. In the present study, the Alinda biplicata 10md-MT gene and a truncated version consisting of one β3 domain and a single C-terminal β1 domain ( 2d-MT ) were introduced into a Caenorhabditis elegans knock-out strain lacking a native MT gene ( mtl-1 ). The two snail MT constructs consistently increased Cd 2+ resistance, and partially improved morphological, life history and physiological fitness traits in the nematode model host Caenorhabditis elegans . This highlights how the engineering of transgenic Caenorhabditis elegans strains expressing snail MTs provides an enhancement of the innate metal detoxification mechanism and in doing so provides a platform for enhanced mechanistic toxicology.

Human fumarylacetoacetate hydrolase (FAH) domain containing protein 1 (FAHD1) is a mitochondrial oxalocatate decarboxylase, the first of its kind identified in eukaryotes. The physiological role of FAHD1 in other eukaryotes is still poorly understood. In C. elegans loss of the FAHD1 ortholog FAHD-1 was reported to impair mitochondrial function, locomotion and egg-laying behavior, yet the underlying mechanisms remained unclear. Using tissue-specific rescue of fahd-1(-) worms, we find that these phenotypic abnormalities are at least in part due to fahd-1's function in neurons. Moreover, we show that egg-laying defects in fahd-1(-) worms can be fully rescued by external dopamine administration and that depletion of fahd-1 expression induces expression of several enzymes involved in serotonin biosynthesis. Together, our results support a role for fahd-1 in modulating serotonin levels and suggest this protein as a novel link between metabolism and neurotransmitter signaling in the nervous system. Finally, we propose a model to explain how a metabolic defect could ultimately lead to marked changes in neuronal signaling.

People with higher levels of neuroticism seem to have drawn the short straw of personality. However, there are multiple ways to score highly in neuroticism. Analyses of the short scale of the Eysenck Personality Questionnaire-Revised in three large data sets have revealed that higher neuroticism can mean having elevated scores on all items, elevated scores mainly on items related to anxiety and tension, or elevated scores mainly on items related to worry and vulnerability. Epidemiological and molecular genetic studies have revealed that people in the first group are at greater risk for poorer mental and physical health but that people in the latter two groups, especially those beset by worry and feelings of vulnerability, have better physical health. These findings suggest that future research on neuroticism and health should focus on different ways that people can exhibit high neuroticism.

A bstract We consider a microscopic analogue of the BMS analysis of asymptotic symmetries by analysing universal geometric structures on infinitesimal tangent light cones. Thereby, two natural microscopic symmetry groups arise: a non-trivially represented Lorentz group and a BMS-like group. The latter has a rich mathematical structure, since it contains the former as a non-canonical subgroup, next to infinitely many other Lorentz subgroups. None of those Lorentz subgroups appears to be intrinsically preferred, and hence, the microscopic BMS-like group constitutes a natural symmetry group for infinitesimal tangent light cones. We compare our investigation with the classical BMS analysis and show, that the microscopic BMS-like group is a gauge group for the bundle of null vectors. Motivated by the various applications of the original BMS group, our findings could have interesting implications: they identify a geometric structure that could be suitable for a bulk analysis of gravitational waves, they suggest a possible enlargement of the fundamental gauge group of gravity and they motivate the possibility of an interrelation between the UV structure of gauge theories, gravitational memory effects and BMS-like symmetries. Also, our results imply, that BMS-like groups arise not only as macroscopic, asymptotic symmetry groups in cosmology, but describe also a fundamental and seemingly unknown microscopic symmetry of pseudo-Riemannian geometry.

Huntington’s disease (HD) is a neurodegenerative disorder caused by poly-Q expansion in the Huntingtin (HTT) protein. Here, we delineate elevated mutant HTT (mHTT) levels in patient-derived cells including fibroblasts and iPSC derived cortical neurons using mesoscale discovery (MSD) HTT assays. HD patients’ fibroblasts and cortical neurons recapitulate aberrant alternative splicing as a molecular fingerprint of HD. Branaplam is a splicing modulator currently tested in a phase II study in HD (NCT05111249). The drug lowers total HTT (tHTT) and mHTT levels in fibroblasts, iPSC, cortical progenitors, and neurons in a dose dependent manner at an IC 50 consistently below 10 nM without inducing cellular toxicity. Branaplam promotes inclusion of non-annotated novel exons. Among these Branaplam-induced exons, there is a 115 bp frameshift-inducing exon in the HTT transcript. This exon is observed upon Branaplam treatment in Ctrl and HD patients leading to a profound reduction of HTT RNA and protein levels. Importantly, Branaplam ameliorates aberrant alternative splicing in HD patients’ fibroblasts and cortical neurons. These findings highlight the applicability of splicing modulators in the treatment of CAG repeat disorders and decipher their molecular effects associated with the pharmacokinetic and -dynamic properties in patient-derived cellular models. Krach et al. dissect the molecular mechanism of the alternative splicing modulator Branaplam in Huntington’s disease. They show that the drug lowers mutant HTT protein levels and ameliorates alternative splicing pathology in an iPSC disease model.

Fumarylacetoacetate hydrolase (FAH) proteins form a superfamily found in Archaea, Bacteria, and Eukaryota. However, few fumarylacetoacetate hydrolase domain (FAHD)-containing proteins have been studied in Metazoa and their role in plants remains elusive. Sequence alignments revealed high homology between two Arabidopsis thaliana FAHD-containing proteins and human FAHD1 (hFAHD1) implicated in mitochondrial dysfunction-associated senescence. Transcripts of the closest hFAHD1 orthologue in Arabidopsis (AtFAHD1a) peak during seed maturation drying, which influences seed longevity and dormancy. Here, a homology study was conducted to assess if AtFAHD1a contributes to seed longevity and vigour. We found that an A. thaliana T-DNA insertional line (Atfahd1a-1) had extended seed longevity and shallower thermo-dormancy. Compared to the wild type, metabolite profiling of dry Atfahd1a-1 seeds showed that the concentrations of several amino acids, some reducing monosaccharides, and δ-tocopherol dropped, whereas the concentrations of dehydroascorbate, its catabolic intermediate threonic acid, and ascorbate accumulated. Furthermore, the redox state of the glutathione disulphide/glutathione couple shifted towards a more reducing state in dry mature Atfahd1a-1 seeds, suggesting that AtFAHD1a affects antioxidant redox poise during seed development. In summary, AtFAHD1a appears to be involved in seed redox regulation and to affect seed quality traits such as seed thermo-dormancy and longevity.

Studies of personality traits in common marmosets ( Callithrix jacchus ) indicate that there are five or six constructs—Sociability, Dominance, Neuroticism, Openness, and two related to Conscientiousness. The present study attempted to determine whether our earlier study of laboratory-housed individuals only yielded three—Dominance, Sociability, and Neuroticism—because of a low amount of between-subjects variance. To do so, we increased our sample size from 77 to 128. In addition, we ascertained the reliability and validity of ratings and whether polymorphisms related to the serotonin 1a receptor were associated with personality. We found Sociability, Dominance, and Negative Affect factors that resembled three domains found in previous studies, including ours. We also found an Openness and Impulsiveness factor, the latter of which bore some resemblance to Conscientiousness, and two higher-order factors, Pro-sociality and Boldness. In further analyses, we could not exclude the possibility that Pro-sociality and Boldness represented a higher-level of personality organization. Correlations between personality factors and well-being were consistent with the definitions of the factors. There were no significant associations between personality and genotype. These results suggest that common marmoset personality structure varies as a function of rearing or housing variables that have not yet been investigated systematically.