Biology subjects

Langer, L.

Publications and source records attributed to Langer, L..

4 recordsLinked to original sources

bioRxiv2026

Experimental evidence for antagonistic effects of sperm competition in two sea urchin species

Sperm competition can occur when sperm from two or more males compete for fertilization of a batch of eggs. While it has been extensively studied in internal fertilizers, it remains poorly under-stood in external fertilizers. To investigate how sperm competition affects fertilization under sperm limitation, we conducted controlled experiments on two sea urchin species: Paracentrotus lividus and Dendraster excentricus. Eggs from a single female were exposed to sperm from three individ-ual males separately (non-competitive treatment) or to a pooled sample from three males (competi-tive treatment). We measured fertilization success as proportion of eggs fertilized after two hours and assessed sperm motility as percentage of motile sperm and curvilinear velocity. For P. lividus , we estimated the sperm concentrations where fertilization success was 50% of maximum observed fertilization success (F50), and the fertilization efficiency of the sperm (Fe), i.e. the likelihood that a sperm - egg encounter results in a fertilizing contact, using the fertilization kinetics model of Styan (1998). For D. excentricus, fertilization success was measured at a sperm concentration expected to produce 50% fertilization success. Sperm competition reduced fertilization success and increased F50 compared to non-competitive treatments, suggesting antagonistic effects that may compromise fertilization under sperm-limited conditions in external fertilizers.

evolutionary biology↗

bioRxiv2025

Langerhans Cell-targeted mRNA Delivery: A Strategy for Dose-Sparing and Enhanced Anti-Tumor Immunity

Despite the success of mRNA therapeutics, challenges remain in optimizing immune responses and minimizing side effects. Cell-specific antigen delivery may help reduce required doses and improve vaccine efficacy. In this study, we report on the first targeted delivery system for mRNA to a specific subset of skin-resident antigen-presenting cells - Langerhans cells. By functionalizing lipid nanoparticles (LNPs) with a langerin-specific glycomimetic ligand, we achieve selective mRNA delivery to both murine and human primary Langerhans cells with minimal off-target uptake, at the same time resulting in significantly increased mRNA translation. This targeted mRNA delivery not only enhances antigen presentation and T cell responses but also enables dose-sparing and superior anti-tumor immunity compared to conventional immunization in a B16-OVA tumor model. Importantly, our platforms high compatibility with various lipid nanoparticle formulations offers a flexible and precise tool for skin-directed mRNA delivery.

immunology↗

bioRxiv2024

Aberrant and Ectopic Cell Populations of the Fibrotic Pushing Border in Restrictive Allograft Syndrome after Lung Transplantation

RationaleRestrictive allograft syndrome (RAS) is a major cause of mortality in patients following lung transplantation due to rapid progressive fibrosis in the pulmonary graft. We have only limited knowledge of the cellular and molecular mechanisms that characterize the fibrosis in the RAS lung. ObjectiveTo elucidate cellularly-resolved transcriptomic and histologic characteristics of the structural cells in human RAS lungs. MethodsSingle-nuclei RNA-sequencing was performed in peripheral lung tissues from 15 RAS patients undergoing lung re-transplantation, and from 9 healthy control lungs. Findings were validated and complemented by various histologic techniques, including immunofluorescence, RNAscope, combined Elastica van Gieson-immunohistochemistry stains, and micro-CT scans. Measurement and Main resultsDifferential gene expression analysis of our single-nuclei RNA-sequencing data revealed in human RAS lungs previously undescribed and uniquely distributed aberrant basaloid cells, ectopic COL15A1+ vascular endothelial cells, and CTHRC1+ fibrotic fibroblasts, all first characterized in idiopathic pulmonary fibrosis (IPF). In contrast to IPF, RAS lacks the cellular equivalent of bronchiolization. Histologic stains confirmed our transcriptomic discoveries and disclosed distinctive distribution patterns: Aberrant basaloid cells are primarily localized at the edge of the fibrotic pushing border, forming together with the juxtaposed CTHRC1+ fibrotic fibroblasts the fibrotic niche of alveolar fibroelastosis (AFE), the histopathological hallmark in RAS lungs. On the endothelial side, PRX+ alveolar microvasculature is lost in AFE areas. Micro-CT scans revealed that blood supply, now facilitated by expanded and ectopic COL15A1+ VE cells, changes from pulmonary to systemic perfusion. Last, our data reveals potential therapeutically-modifiable expression patterns in RAS, including genes coding for the integrin subunits v{beta}6, activators of TGF{beta}. ConclusionConsidering the marked clinical, histologic and etiologic dissimilarities of RAS and IPF, our snRNAseq study revealed a surprising general principle of cellular and molecular pathogenesis in the fibrosing lung: the entity-spanning composition of the fibrotic niche by a) aberrant basaloid cells localized at the fibrotic pushing border, b) ectopic COL15A1+ vascular ECs and c) effector CTHRC1+ fibrotic fibroblasts. This general principle justifies a flexible but cellular pathogenesis-guided transferability of potential therapeutic approaches between progressive fibrotic lung diseases.

cell biology↗

bioRxiv2021

Mito-nuclear variation in transgenerational and reproductive effects of amino acid and lipid nutrition

Epistasis between mitochondrial and nuclear genomes can modulate fitness effects of nutrition. Are these "mitonuclear" effects deterministic with regard to optimal nutrition? Which nutrients and genetic loci participate? Here, in fruitflies, we show that mitonuclear epistasis repeatably dictates fitness effects of dietary lipids and amino acids, with a tripartite interaction emerging as an unprecedented source of quantitative variation. We also observed diet-dependent developmental lethality and parental effects, but only in specific mitonucleotypes. Associating phenotype to mtDNA variation implicated a non-coding RNA (mt:lrRNA), suggesting a novel mechanism, with epistasis between mitochondria-derived regulatory factors and the nuclear genome producing qualitative differences in how diet impacts fitness. SUMMARYCombined action of nuclear genotype and regulatory loci on mtDNA produces major differences in fitness impacts of nutrition.

genetics↗