Exploring the Critical Role of Tight Junction Proteins in Kidney Disease Pathogenesis.

Background: Kidney disease poses a significant global health challenge, marked by a rapid decline in renal function due to a variety of causative factors. A crucial element in the pathophysiology of kidney disease is the dysregulation of epithelial cells, which are vital components of renal tissue architecture. The integrity and functionality of these cells are largely dependent on tight junctions (TJ) proteins, complex molecular structures that link adjacent epithelial cells.

Two-Dimensional Turbulence with Local Interactions: Statistics of the Condensate.

Two-dimensional turbulence self-organizes through a process of energy accumulation at large scales, forming a coherent flow termed a condensate. We study the condensate in a model with local dynamics, the large-scale quasigeostrophic equation, observed here for the first time. We obtain analytical results for the mean flow and the two-point, second-order correlation functions, and validate them numerically.

Turbulence Statistics in a Two-Dimensional Vortex Condensate.

Disentangling the evolution of a coherent mean-flow and turbulent fluctuations, interacting through the nonlinearity of the Navier-Stokes equations, is a central issue in fluid mechanics. It affects a wide range of flows, such as planetary atmospheres, plasmas, or wall-bounded flows, and hampers turbulence models. We consider the special case of a two-dimensional flow in a periodic box, for which the mean flow, a pair of box-size vortices called "condensate," emerges from turbulence.

Predictability of escape for a stochastic saddle-node bifurcation: When rare events are typical.

Transitions between multiple stable states of nonlinear systems are ubiquitous in physics, chemistry, and beyond. Two types of behaviors are usually seen as mutually exclusive: unpredictable noise-induced transitions and predictable bifurcations of the underlying vector field. Here, we report a different situation, corresponding to a fluctuating system approaching a bifurcation, where both effects collaborate.

Approaches targeting the FGF-FGFR system: a review of the recent patent literature and associated advanced therapeutic agents.

Fibroblast growth factor receptors (FGFRs) and associated ligands (FGFs) are a family of well-validated targets for therapeutic interventions notably in cancer diseases in relation to their prominent roles in cell growth, survival, differentiation and angiogenesis. This patent review encompasses all different approaches (modulators of FGF or FGFR expression, anti-FGF antibodies, anti-FGFR antibodies, FGF traps, tyrosine-kinase (TK) inhibitors, allosteric modulators) used to block completely or partially the activities of the FGF-FGFR complexes resulting in clinical drug candidates or tool agents. Comparative analysis of biochemical, pharmacological or clinical data will be discussed for each class of molecules together with some perspectives.

Nonlinear energy transfers and phase diagrams for geostrophically balanced rotating-stratified flows.

Equilibrium statistical mechanics tools have been developed to obtain indications about the natural tendencies of nonlinear energy transfers in two-dimensional and quasi-two-dimensional flows like rotating and stratified flows in geostrophic balance. In this article we consider a simple model of such flows with a nontrivial vertical structure, namely, two-layer quasigeostrophic flows, which remain amenable to analytical study. We obtain the statistical equilibria of the system in the case of a linear vorticity-stream function relation, build the corresponding phase diagram, and discuss the most probable outcome of nonlinear energy transfers, both on the horizontal and on the vertical, in the presence of stratification and rotation.

Restricted partition functions and inverse energy cascades in parity symmetry breaking flows.

When the symmetries of homogenous isotropic turbulent flows are broken, different sets of modes with different physical roles emerge. In particular, choosing a forcing which puts more weight on one or the other of these sets may result in different statistics for the energy transfers. We use the general method of computing a partition function restricted to a portion of phase space to study analytically these different statistics.

Molecular mechanism of SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of FGF receptor signaling.

The fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling network plays an important role in cell growth, survival, differentiation, and angiogenesis. Deregulation of FGFR signaling can lead to cancer development. Here, we report an FGFR inhibitor, SSR128129E (SSR), that binds to the extracellular part of the receptor.

Transgenic sequences are frequently lost in Phytophthora parasitica transformants without reversion of the transgene-induced silenced state.

Little data exist on the mechanism and stability of transformation in Phytophthora parasitica, a major oomycete parasite of plants. Here, we studied the stability of drug-resistant protoplast transformants by analyzing single-zoospore derivatives. We show that the transgenic sequences are not stably integrated into the chromosomes, resulting in the loss of drug resistance in single-zoospore derivatives.

Regulation and role of a STE12-like transcription factor from the plant pathogen Colletotrichum lindemuthianum.

In phytopathogenic fungi, STE12-like genes encode transcription factors essential for appressorium-mediated host penetration. However, their regulation and downstream targets are still unknown. In the present study, a STE12-like gene (CLSTE12) from Colletotrichum lindemuthianum was isolated.

Functional analysis of CLPT1, a Rab/GTPase required for protein secretion and pathogenesis in the plant fungal pathogen Colletotrichum lindemuthianum.

In eukaryotic cells, Rab/GTPases are major regulators of vesicular trafficking and are involved in essential processes including exocytosis, endocytosis and cellular differentiation. To investigate the role of these proteins in fungal pathogenicity, a dominant-negative mutant allele of CLPT1, a Rab/GTPase of the bean pathogen Colletotrichum lindemuthianum, was expressed in transgenic strains. This mutated gene encodes the amino-acid substitution N123I analogous to the N133I substitution in a known trans-dominant inhibitor of the Sec4 Rab/GTPase from Saccharomyces cerevisiae.

Production of a cell wall-associated endopolygalacturonase by Colletotrichum lindemuthianum and pectin degradation during bean infection.

The bean pathogen Colletotrichum lindemuthianum expresses two endopolygalacturonase genes, CLPG1 and CLPG2, during interaction with its host plant. However, only CLPG1 was found to be secreted to the extracellular medium during saprophytic growth of the fungus on pectin. To localize CLPG2, a FLAG epitope sequence was inserted in the C-terminal sequence of CLPG2 and the modified gene was introduced into C.

A cis-acting sequence homologous to the yeast filamentation and invasion response element regulates expression of a pectinase gene from the bean pathogen Colletotrichum lindemuthianum.

Phytopathogenic fungi secrete hydrolytic enzymes that degrade plant cell walls, notably pectinases. The signaling pathway(s) that control pectinase gene expression are currently unknown in filamentous fungi. Recently, the green fluorescent protein coding sequence was used as a reporter gene to study the expression of CLPG2, a gene encoding an endopolygalacturonase of the bean pathogen Colletotrichum lindemuthianum.