Influence of personality, age, sex, and oestrus state on chimpanzee problem-solving success

Despite the importance of individual problem solvers for group- and individual-level fitness, the correlates of individual problem-solving success are still an open topic of investigation. In addition to demographic factors, such as age or sex, certain personality dimensions have also been revealed as reliable correlates of problem-solving by animals. Such correlates, however, have been little-studied in chimpanzees. To empirically test the influence of age, sex, estrous state, and different personality factors on chimpanzee problem-solving, we individually tested 36 captive chimpanzees with two novel foraging puzzles. We included both female (N = 24) and male (N = 12) adult chimpanzees (aged 14–47 years) in our sample. We also controlled for the females’ estrous state—a potential influence on cognitive reasoning—by testing cycling females both when their sexual swelling was maximally tumescent (associated with the luteinizing hormone surge of a female’s estrous cycle) and again when it was detumescent. Although we found no correlation between the chimpanzees’ success with either puzzle and their age or sex, the chimpanzees’ personality ratings did correlate with responses to the novel foraging puzzles. Specifically, male chimpanzees that were rated highly on the factors Methodical, Openness (to experience), and Dominance spent longer interacting with the puzzles. There was also a positive relationship between the latency of females to begin interacting with the two tasks and their rating on the factor Reactivity/Undependability. No other significant correlations were found, but we report tentative evidence for increased problem-solving success by the females when they had detumescent estrous swellings

Genetic variants in the LAMA5 gene in pediatric nephrotic syndrome

Item does not contain fulltextBACKGROUND: Nephrotic syndrome (NS), a chronic kidney disease, is characterized by significant loss of protein in the urine causing hypoalbuminemia and edema. In general, approximately 15% of childhood-onset cases do not respond to steroid therapy and are classified as steroid-resistant NS (SRNS). In approximately 30% of cases with SRNS, a causative mutation can be detected in one of 44 monogenic SRNS genes. The gene LAMA5 encodes laminin-alpha5, an essential component of the glomerular basement membrane. Mice with a hypomorphic mutation in the orthologous gene Lama5 develop proteinuria and hematuria. METHODS: To identify additional monogenic causes of NS, we performed whole exome sequencing in 300 families with pediatric NS. In consanguineous families we applied homozygosity mapping to identify genomic candidate loci for the underlying recessive mutation. RESULTS: In three families, in whom mutations in known NS genes were excluded, but in whom a recessive, monogenic cause of NS was strongly suspected based on pedigree information, we identified homozygous variants of unknown significance (VUS) in the gene LAMA5. While all affected individuals had nonsyndromic NS with an early onset of disease, their clinical outcome and response to immunosuppressive therapy differed notably. CONCLUSION: We here identify recessive VUS in the gene LAMA5 in patients with partially treatment-responsive NS. More data will be needed to determine the impact of these VUS in disease management. However, familial occurrence of disease, data from genetic mapping and a mouse model that recapitulates the NS phenotypes suggest that these genetic variants may be inherited factors that contribute to the development of NS in pediatric patients

Dissecting the treatment-naive ecosystem of human melanoma brain metastasis.

Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spatial single-cell transcriptomics and T cell receptor (TCR)-seq. Cancer cells from MBM were more chromosomally unstable, adopted a neuronal-like cell state, and enriched for spatially variably expressed metabolic pathways. Key observations were validated in independent patient cohorts, patient-derived MBM/ECM xenograft models, RNA/ATAC-seq, proteomics, and multiplexed imaging. Integrated spatial analyses revealed distinct geography of putative cancer immune evasion and evidence for more abundant intra-tumoral B to plasma cell differentiation in lymphoid aggregates in MBM. MBM harbored larger fractions of monocyte-derived macrophages and dysfunctional TOX <sup>+</sup> CD8 <sup>+</sup> T cells with distinct expression of immune checkpoints. This work provides comprehensive insights into MBM biology and serves as a foundational resource for further discovery and therapeutic exploration