Biology subjects

Denise, H.

Publications and source records attributed to Denise, H..

3 recordsLinked to original sources

bioRxiv2026

Targeting skin ageing at the source: a novel cellular reprogramming approach using natural extract combinations

Cellular senescence is a driver of skin ageing that leads to structural deterioration and aesthetic changes. This study evaluated a novel senomorphic strategy, using synergistic combinations of natural small molecules to target RNA splicing regulation via upstream ERK/AKT signaling pathways. Nature-identical synthetic molecules, and corresponding extracts were assessed for cytotoxicity, impact on senescent cell load, proliferation, DNA damage load and SASP markers in naturally aged human primary skin cells. A topical, simple formulation was evaluated for impact on senescence and skin structure using 3D human ex vivo full-thickness skin explants exposed to 1.5 J/cm2 UVC irradiation. Combination of H. lupulus and G. biloba extracts produced a dose-dependent senomorphic impact of up to 45% in aged dermal fibroblasts and 10% in aged human primary keratinocytes (p [≤] 0.0001 & 0.001), without inducing cell proliferation. A 50% decrease in DNA damage load was also observed (p [≤] 0.0001). Qualitatively, the simple formulation mitigated UV-induced epidermal hyperplasia, restored collagen fiber organization, and reduced markers of senescence and inflammation. Targeting cellular senescence is an emerging traction point to address the root biological causes of skin ageing. Targeting the splicing dysregulation/senescence axis using combinations of natural plant extracts may provide a novel mode of action to reprogram senescent cells for repair and protection of skin structure and function.

cell biology↗

bioRxiv2021

Differential use of multiple genetic sex determination systems in divergent ecomorphs of an African crater lake cichlid

African cichlid fishes not only exhibit remarkably high rates of speciation but also have some of the fastest evolving sex determination systems in vertebrates. However, little is known empirically in cichlids about the genetic mechanisms generating new sex-determining variants, what forces dictate their fate, the demographic scales at which they evolve, and whether they are related to speciation. To address these questions, we looked for sex-associated loci in full genome data from 647 individuals of Astatotilapia calliptera from Lake Masoko, a small isolated crater lake in Tanzania, which contains two distinct ecomorphs of the species. We identified three separate XY systems on recombining chromosomes. Two Y alleles derive from mutations that increase expression of the gonadal soma-derived factor gene (gsdf) on chromosome 7; the first is a tandem duplication of the entire gene observed throughout much of the Lake Malawi haplochromine cichlid radiation to which A. calliptera belongs, and the second is a 5 kb insertion directly upstream of gsdf. Both the latter variant and another 700 bp insertion on chromosome 19 responsible for the third Y allele arose from transposable element insertions. Males belonging to the Masoko deep-water benthic ecomorph are determined exclusively by the gsdf duplication, whereas all three Y alleles are used in the Masoko littoral ecomorph, in which they appear to act antagonistically among males with different amounts of benthic admixture. This antagonism in the face of ongoing admixture may be important for sustaining multifactorial sex determination in Lake Masoko. In addition to identifying the molecular basis of three coexisting sex determining alleles, these results demonstrate that genetic interactions between Y alleles and genetic background can potentially affect fitness and adaptive evolution.

evolutionary biology↗

bioRxiv2018

Microbial adaptation to venom is common in snakes and spiders

Animal venoms are considered sterile sources of antimicrobial compounds with strong membrane disrupting activity against multi-drug resistant bacteria. However, bite wound infections are common in developing nations. Investigating the oral and venom microbiome of five snake and two spider species, we evidence viable microorganisms potentially unique to venom for black-necked spitting cobras (Naja nigricollis). Among these are two venom-resistant novel sequence types of Enterococcus faecalis; the genome sequence data of these isolates feature an additional 45 genes, nearly half of which improve membrane integrity. Our findings challenge the dogma of venom sterility and indicate an increased primary infection risk in the clinical management of venomous animal bite wounds. One Sentence SummaryIndependent bacterial colonization of cobra venom drives acquisition of genes antagonistic to venom antimicrobial peptides.

microbiology↗