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John the Baptist in Leonardo Da Vinci's Painting - What's in a Smile?
Clin Dermatol
January 2025
Agnes Irwin School. Rosemont, Pennsylvania, USA.
The smile is a complex human facial expression, most commonly associated with joy. We present a detailed view on Leonardo Da Vinci's painting of Saint John the Baptist, between 1516 to 1516, which illustrates a smiling saint, which has evoked multiple explanations and theories. Discussing Da Vinci's concept of painting as science media and the two merely contradictory painting techniques chiaroscuro and sfumato, we attempt to approach this picture.
View Article and Find Full Text PDFRefining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.
Nat Genet
January 2025
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.
View Article and Find Full Text PDFDiscovery of High-Affinity SMARCA2/4 Bromodomain Ligands and Development of Potent and Exceptionally Selective SMARCA2 PROTAC Degraders.
J Med Chem
January 2025
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.
In the SWI/SNF chromatin-remodeling complex, the mutually exclusive catalytic ATPase subunits SMARCA2 and SMARCA4 proteins have a synthetic-lethal relationship. Selectively targeting SMARCA2 for degradation is a promising and new therapeutic strategy for human cancers harboring inactivated mutated SMARCA4. In this study, we report the design, synthesis, and biological evaluation of novel SMARCA2/4 ligands and our subsequent design of PROTAC degraders using high-affinity SMARCA ligands and VHL-1 ligands.
View Article and Find Full Text PDFThe survival of B cells is compromised in kidney disease.
Nat Commun
December 2024
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Antibody-mediated protection against pathogens is crucial to a healthy life. However, the recent SARS-CoV-2 pandemic has shown that pre-existing comorbid conditions including kidney disease account for compromised humoral immunity to infections. Individuals with kidney disease are not only susceptible to infections but also exhibit poor vaccine-induced antibody response.
View Article and Find Full Text PDFEcological and anthropogenic effects on the genomic diversity of lemurs in Madagascar.
Nat Ecol Evol
January 2025
IBE, Institute of Evolutionary Biology (UPF-CSIC), Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Ecological variation and anthropogenic landscape modification have had key roles in the diversification and extinction of mammals in Madagascar. Lemurs represent a radiation with more than 100 species, constituting roughly one-fifth of the primate order. Almost all species of lemurs are threatened with extinction, but little is known about their genetic diversity and demographic history.
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