OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research

Online application for survival analysis (OASIS) has served as a popular and convenient platform for the statistical analysis of various survival data, particularly in the field of aging research. With the recent advances in the fields of aging research that deal with complex survival data, we noticed a need for updates to the current version of OASIS. Here, we report OASIS 2 (http://sbi.postech.ac.kr/oasis2), which provides extended statistical tools for survival data and an enhanced user interface. In particular, OASIS 2 enables the statistical comparison of maximal lifespans, which is potentially useful for determining key factors that limit the lifespan of a population. Furthermore, OASIS 2 provides statistical and graphical tools that compare values in different conditions and times. That feature is useful for comparing age-associated changes in physiological activities, which can be used as indicators of "healthspan." We believe that OASIS 2 will serve as a standard platform for survival analysis with advanced and user-friendly statistical tools for experimental biologists in the field of aging research.1127Ysciescopu

Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2

The mammalian intestine is one of the most rapidly self-renewing tissues, driven by stem cells residing at the crypt bottom. Paneth cells form a major element of the niche microenvironment providing various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt3. Different Wnt ligands can selectively activate β-catenin-dependent (canonical) or -independent (noncanonical) signaling. Here, we report that the Dishevelled-associated activator of morphogenesis 1 (Daam1) and its paralogue Daam2 asymmetrically regulate canonical and noncanonical Wnt (Wnt/PCP) signaling. Daam1/2 interacts with the Wnt inhibitor RNF43, and Daam1/2 double knockout stimulates canonical Wnt signaling by preventing RNF43-dependent degradation of the Wnt receptor, Frizzled (Fzd). Single-cell RNA sequencing analysis revealed that Paneth cell differentiation is impaired by Daam1/2 depletion because of defective Wnt/PCP signaling. Together, we identified Daam1/2 as an unexpected hub molecule coordinating both canonical and noncanonical Wnt, which is fundamental for specifying an adequate number of Paneth cells

Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2

The mammalian intestine is one of the most rapidly self-renewing tissues, driven by stem cells residing at the crypt bottom. Paneth cells form a major element of the niche microenvironment providing various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt3. Different Wnt ligands can selectively activate β-catenin-dependent (canonical) or -independent (noncanonical) signaling. Here, we report that the Dishevelled-associated activator of morphogenesis 1 (Daam1) and its paralogue Daam2 asymmetrically regulate canonical and noncanonical Wnt (Wnt/PCP) signaling. Daam1/2 interacts with the Wnt inhibitor RNF43, and Daam1/2 double knockout stimulates canonical Wnt signaling by preventing RNF43-dependent degradation of the Wnt receptor, Frizzled (Fzd). Single-cell RNA sequencing analysis revealed that Paneth cell differentiation is impaired by Daam1/2 depletion because of defective Wnt/PCP signaling. Together, we identified Daam1/2 as an unexpected hub molecule coordinating both canonical and noncanonical Wnt, which is fundamental for specifying an adequate number of Paneth cells

Identification of druggable PPIs using domain-mediated interaction interfaces

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Bio-Inspired Extreme Wetting Surfaces for Biomedical Applications

Biological creatures with unique surface wettability have long served as a source of inspiration for scientists and engineers. More specifically, materials exhibiting extreme wetting properties, such as superhydrophilic and superhydrophobic surfaces, have attracted considerable attention because of their potential use in various applications, such as self-cleaning fabrics, anti-fog windows, anti-corrosive coatings, drag-reduction systems, and efficient water transportation. In particular, the engineering of surface wettability by manipulating chemical properties and structure opens emerging biomedical applications ranging from high-throughput cell culture platforms to biomedical devices. This review describes design and fabrication methods for artificial extreme wetting surfaces. Next, we introduce some of the newer and emerging biomedical applications using extreme wetting surfaces. Current challenges and future prospects of the surfaces for potential biomedical applications are also addressed

Linear Motif-Mediated Interactions Have Contributed to the Evolution of Modularity in Complex Protein Interaction Networks

<div><p>The modular architecture of protein-protein interaction (PPI) networks is evident in diverse species with a wide range of complexity. However, the molecular components that lead to the evolution of modularity in PPI networks have not been clearly identified. Here, we show that weak domain-linear motif interactions (DLIs) are more likely to connect different biological modules than strong domain-domain interactions (DDIs). This molecular division of labor is essential for the evolution of modularity in the complex PPI networks of diverse eukaryotic species. In particular, DLIs may compensate for the reduction in module boundaries that originate from increased connections between different modules in complex PPI networks. In addition, we show that the identification of biological modules can be greatly improved by including molecular characteristics of protein interactions. Our findings suggest that transient interactions have played a unique role in shaping the architecture and modularity of biological networks over the course of evolution.</p></div

The expansion of DLIs contributed to the increase in modularity of metazoan PPI networks.

<p>(<b>a</b>) Topological modularity, <i>M_PPI</i>, in nine representative eukaryotic species. (<b>b</b>) A schematic showing how increased complexity is associated with <i>M_PPI</i>. (<b>c</b>) Network modularity (<i>M_DLI/DDI</i>) in nine representative eukaryotic species. (<b>d</b>) A schematic showing how DLIs are associated with increased <i>M_DLI/DDI</i>. (<b>e</b>) The evolution of ‘cell-cell adhesion’ and ‘leukocyte migration’ groups is shown as an example.</p

Enrichment of DLIs and DDIs in interactions between and within biological modules.

<p>(<b>a</b>) Odd ratio in functional groups. (<b>b</b>) Two functional groups, ‘cell-cell adhesion’ and ‘leukocyte migration’ were shown. (<b>c</b>) Odd ratio in protein complexes. (<b>d</b>) Two protein complexes, ‘RNA polymerase II’ and ‘BRCA1-associated genome surveillance’ were shown. (<b>e</b>) Odd ratio in subcellular localizations. (<b>f</b>) Two subcellular localizations, ‘cytoplasm’ and ‘nucleus’, were shown.</p

DDI and DLI-assigned human PPI network.

<p>(<b>a</b>) Categorizing human PPIs as DDIs or DLIs. A part of the human PPI network is shown to visualize DDI/DLI-assigned network. (<b>b</b>) Quality assessment of linear motifs during classification process. (<b>c</b>) Comparison of DDIs and DLIs categorized using our method to reference sets. (<b>d</b>) Edge clustering coefficients of DDIs and DLIs in the human PPI network. Grey bars show the distribution of average edge clustering coefficients in 10⁵ networks with randomly assigned DDIs and DLIs.</p