Search bioRxiv⌕ Search

Biology subjects

Fernandez, R. J.

Publications and source records attributed to Fernandez, R. J..

3 recordsLinked to original sources

Edge-focused network-based approach: an improved kernel density estimator for home range

O_LIOne of the central challenges in ecology and animal behaviour is to generate animal home range estimations. Kernel density estimate for home range has been one of the most widely used estimates these last few decades, despite its limitations. More recently a network-based kernel density (NKDE) approach has been proposed, which uses Delaunay triangulation. C_LIO_LIHere we show that NKDE has a discontinuous kernel density. We then develop a new network-based method that emphasises entirely on the edges, instead of the nodes in the network. We call this Edge-Focused Network-based Kernel Density Estimation (EFNKDE). In this method, a unit weight is distributed uniformly along each edge of the network and Euclidean distance is used to compute the contribution of each segment of the edge to the kernel density at a given point. C_LIO_LIThis is a network based method that leads to a continuous and differentiable kernel density. An analytical expression for the same is obtained for the Gaussian kernel. By taking concrete examples and studying different methods and through different perspectives across a range of bandwidths, we show that EFNKDE has many advantages over other methods. We present a model that provides a theoretical basis to the effectiveness of EFNKDE in linear regimes. C_LIO_LIEFNKDE is easy to apply, can work with minimal data, provides a smooth kernel density that highlights the network and does not overemphasise the data. This method is most suitable for estimating home ranges with narrow corridors and forbidden regions. C_LI

ecology↗

Patient induced pluripotent stem cell-derived hepatostellate organoids establish a basis for liver pathologies in telomeropathies

Patients with dyskeratosis congenita (DC) and related telomeropathies resulting from premature telomere dysfunction suffer from multi-organ failure. In the liver, DC patients present with nodular hyperplasia, steatosis, inflammation, and cirrhosis. We model DC liver pathologies using isogenic human induced pluripotent stem (iPS) cells harboring a causal DC mutation in DKC1, or a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-corrected control allele. Differentiation of these iPS cells into hepatocytes or hepatic stellate cells followed by generation of genotype-admixed hepatostellate organoids revealed a dominant phenotype in the parenchyma, with DC hepatocytes eliciting a pathogenic hyperplastic response in stellate cells independent of stellate cell genotype. Pathogenic phenotypes could be rescued via suppression of AKT activity, a central regulator of MYC-driven hyperplasia downstream of DKC1 mutation. Thus, isogenic iPS-derived admixed hepatostellate organoids offer insight into the liver pathologies in telomeropathies and provide a framework for evaluating emerging therapies.

cell biology↗

GSK3 inhibition rescues growth and telomere dysfunction in dyskeratosis congenita iPSC-derived type II alveolar epithelial cells

Dyskeratosis congenita (DC) is a rare genetic disorder characterized by deficiencies in telomere maintenance leading to very short telomeres and the premature onset of certain age-related diseases, including pulmonary fibrosis (PF). PF is thought to derive from epithelial failure, particularly that of type II alveolar epithelial (AT2) cells, which are highly dependent on Wnt signaling during development and adult regeneration. We use human iPSC-derived AT2 (iAT2) cells to model how short telomeres affect AT2 cells. Cultured DC mutant iAT2 cells accumulate shortened, uncapped telomeres and manifest defects in the growth of alveolospheres, hallmarks of senescence, and apparent defects in Wnt signaling. The GSK3 inhibitor, CHIR99021, which mimics the output of canonical Wnt signaling, enhances telomerase activity and rescues the defects. These findings support further investigation of Wnt agonists as potential therapies for DC related pathologies.

cell biology↗