Microenvironmental entropy dynamics analysis reveals novel insights into Notch-Delta-Jagged decision-making mechanism.

Notch-Delta-Jagged (NDJ) signaling among neighboring cells contributes crucially to spatiotemporal pattern formation and developmental decision-making. Despite numerous detailed mathematical models, their high-dimensionality parametric space limits analytical treatment, especially regarding local microenvironmental fluctuations. Using the low-dimensional dynamics of the recently postulated least microenvironmental uncertainty principle (LEUP) framework, we showcase how the LEUP formalism recapitulates a noisy NDJ spatial patterning.

Emergent dynamics of underlying regulatory network links EMT and androgen receptor-dependent resistance in prostate cancer.

Advanced prostate cancer patients initially respond to hormone therapy, be it in the form of androgen deprivation therapy or second-generation hormone therapies, such as abiraterone acetate or enzalutamide. However, most men with prostate cancer eventually develop hormone therapy resistance. This resistance can arise through multiple mechanisms, such as through genetic mutations, epigenetic mechanisms, or through non-genetic pathways, such as lineage plasticity along epithelial-mesenchymal or neuroendocrine-like axes.

Spatiotemporal Patterning Enabled by Gene Regulatory Networks.

Spatiotemporal pattern formation plays a key role in various biological phenomena including embryogenesis and neural network formation. Though the reaction-diffusion systems enabling pattern formation have been studied phenomenologically, the biomolecular mechanisms behind these processes have not been modeled in detail. Here, we study the emergence of spatiotemporal patterns due to simple, synthetic and commonly observed two- and three-node gene regulatory network motifs coupled with their molecular diffusion in one- and two-dimensional space.

Identification and functional characterization of mRNAs that exhibit stop codon readthrough in Arabidopsis thaliana.

Stop codon readthrough (SCR) is the process of continuation of translation beyond the stop codon, generating protein isoforms with C-terminal extensions. SCR has been observed in viruses, fungi, and multicellular organisms, including mammals. However, SCR is largely unexplored in plants.

Intrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma.

Intrinsically disordered proteins (IDPs) are proteins that lack rigid 3D structure. Hence, they are often misconceived to present a challenge to Anfinsen's dogma. However, IDPs exist as ensembles that sample a quasi-continuum of rapidly interconverting conformations and, as such, may represent proteins at the extreme limit of the Anfinsen postulate.

Coupled Feedback Loops Involving PAGE4, EMT and Notch Signaling Can Give Rise to Non-genetic Heterogeneity in Prostate Cancer Cells.

Non-genetic heterogeneity is emerging as a crucial factor underlying therapy resistance in multiple cancers. However, the design principles of regulatory networks underlying non-genetic heterogeneity in cancer remain poorly understood. Here, we investigate the coupled dynamics of feedback loops involving (a) oscillations in androgen receptor (AR) signaling mediated through an intrinsically disordered protein PAGE4, (b) multistability in epithelial-mesenchymal transition (EMT), and c) Notch-Delta-Jagged signaling mediated cell-cell communication, each of which can generate non-genetic heterogeneity through multistability and/or oscillations.

Emergent Properties of the HNF4α-PPARγ Network May Drive Consequent Phenotypic Plasticity in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in adults and children. It is characterized by excessive accumulation of lipids in the hepatocytes of patients without any excess alcohol intake. With a global presence of 24% and limited therapeutic options, the disease burden of NAFLD is increasing.