Typhoid toxin exhausts the RPA response to DNA replication stress driving senescence and Salmonella infection.

Salmonella Typhi activates the host DNA damage response through the typhoid toxin, facilitating typhoid symptoms and chronic infections. Here we reveal a non-canonical DNA damage response, which we call RING (response induced by a genotoxin), characterized by accumulation of phosphorylated histone H2AX (γH2AX) at the nuclear periphery. RING is the result of persistent DNA damage mediated by toxin nuclease activity and is characterized by hyperphosphorylation of RPA, a sensor of single-stranded DNA (ssDNA) and DNA replication stress. The toxin overloads the RPA pathway with ssDNA substrate, causing RPA exhaustion and senescence. Senescence is also induced by canonical γΗ2ΑΧ foci revealing distinct mechanisms. Senescence is transmitted to non-intoxicated bystander cells by an unidentified senescence-associated secreted factor that enhances Salmonella infections. Thus, our work uncovers a mechanism by which genotoxic Salmonella exhausts the RPA response by inducing ssDNA formation, driving host cell senescence and facilitating infection

Possibilities of using branched-chain amino acids for the treatment and prevention of sarcopenia in elderly and old patients (literature review)

Due to the high prevalence of sarcopenia among elderly and old patients, early prevention and treatment of sarcopenia and its complications are relevant. Protein supplements can be used to maintain muscle strength and mass during aging. The possibility of using branched-chain amino acids (BCAAs) in the treatment and prevention of sarcopenia in geriatric patients is of scientific interest. BCAAs promote the synthesis and inhibit the degradation of muscle tissue proteins, are involved in the regulation of tissue sensitivity to insulin, ammonia utilization, the tricarboxylic acid cycle, etc.Search strategy. The search for scientific articles for literature review was carried out in the PubMed and PubMed Central databases. The selection criterion was scientific articles published up to December 2022. We used the following search keywords: “branched-chain amino acids”, “BCAA”, “body composition”, “sarcopenia”, “aging”. The 2019 European Working Group on Sarcopenia in Older People 2 (EWGSOP2) Consensus was included in the list of articles.Conclusions. The possibility of using BCAAs in elderly and old patients for the prevention and treatment of sarcopenia is a relevant topic that continues to be actively studied. The effectiveness of BCAA supplementation in the diet is debatable as long as sufficient protein is consumed daily. On the other hand, BCAA supplementation may be justified in cases where it is not possible to consume enough high-quality protein in the diet. More research is needed on this topic

Modularity in Protein Complex and Drug Interactions Reveals New Polypharmacological Properties

Recent studies have highlighted the importance of interconnectivity in a large range of molecular and human disease-related systems. Network medicine has emerged as a new paradigm to deal with complex diseases. Connections between protein complexes and key diseases have been suggested for decades. However, it was not until recently that protein complexes were identified and classified in sufficient amounts to carry out a large-scale analysis of the human protein complex system. We here present the first systematic and comprehensive set of relationships between protein complexes and associated drugs and analyzed their topological features. The network structure is characterized by a high modularity, both in the bipartite graph and in its projections, indicating that its topology is highly distinct from a random network and that it contains a rich and heterogeneous internal modular structure. To unravel the relationships between modules of protein complexes, drugs and diseases, we investigated in depth the origins of this modular structure in examples of particular diseases. This analysis unveils new associations between diseases and protein complexes and highlights the potential role of polypharmacological drugs, which target multiple cellular functions to combat complex diseases driven by gain-of-function mutations

Ultrafast laser micro-nano structuring of transparent materials with high aspect ratio

Ultrafast lasers are ideal tools to process transparent materials because they spatially confine the deposition of laser energy within the material's bulk via nonlinear photoionization processes. Nonlinear propagation and filamentation were initially regarded as deleterious effects. But in the last decade, they turned out to be benefits to control energy deposition over long distances. These effects create very high aspect ratio structures which have found a number of important applications, particularly for glass separation with non-ablative techniques. This chapter reviews the developments of in-volume ultrafast laser processing of transparent materials. We discuss the basic physics of the processes, characterization means, filamentation of Gaussian and Bessel beams and provide an overview of present applications