Alzheimer’s disease is the most common type of neurodegenerative disease in the world. Genetic evidence strongly suggests that aberrant generation, aggregation, and/or clearance of neurotoxic amyloid-β peptides (Aβ) triggers the disease. Aβ accumulates at the points of contact of neurons in ordered cords and fibrils, forming the so-called senile plaques. Aβ isoforms of different lengths are found in healthy human brains regardless of age and appear to play a role in signaling pathways in the brain and to have neuroprotective properties at low concentrations. In recent years, different substances have been developed targeting Aβ production, aggregation, interaction with other molecules, and clearance, including peptide-based drugs. Aβ is a product of sequential cleavage of the membrane glycoprotein APP (amyloid precursor protein) by β- and γ-secretases. A number of familial mutations causing an early onset of the disease have been identified in the APP, especially in its transmembrane domain. The mutations are reported to influence the production, oligomerization, and conformational behavior of Aβ peptides. This review highlights the results of structural studies of the main proteins involved in Alzheimer’s disease pathogenesis and the molecular mechanisms by which perspective therapeutic substances can affect Aβ production and nucleation.

Plant protoplasts are widely used for genetic manipulation and functional studies in transient expression systems. However, little is known about the molecular pathways involved in a cell response to the combined stress factors resulted from protoplast generation. Plants often face more than one type of stress at a time, and how plants respond to combined stress factors is therefore of great interest. Here, we used protoplasts of the moss Physcomitrella patens as a model to study the effects of short-term stress on the chloroplast proteome. Using label-free comparative quantitative proteomic analysis (SWATH-MS), we quantified 479 chloroplast proteins, 219 of which showed a more than 1.4-fold change in abundance in protoplasts. We additionally quantified 1451 chloroplast proteins using emPAI. We observed degradation of a significant portion of the chloroplast proteome following the first hour of stress imposed by the protoplast isolation process. Electron-transport chain (ETC) components underwent the heaviest degradation, resulting in the decline of photosynthetic activity. We also compared the proteome changes to those in the transcriptional level of nuclear-encoded chloroplast genes. Globally, the levels of the quantified proteins and their corresponding mRNAs showed limited correlation. Genes involved in the biosynthesis of chlorophyll and components of the outer chloroplast membrane showed decreases in both transcript and protein abundance. However, proteins like dehydroascorbate reductase 1 and 2-cys peroxiredoxin B responsible for ROS detoxification increased in abundance. Further, genes such as thylakoid ascorbate peroxidase were induced at the transcriptional level but down-regulated at the proteomic level. Together, our results demonstrate that the initial chloroplast reaction to stress is due changes at the proteomic level.

We present a multimodal multi-species multi-omics multi-tissue transformer for aging research and drug discovery capable of performing multiple tasks such as age prediction across species, target discovery, tissue, sex, and disease sample classification, drug sensitivity prediction, replication of omics response and prediction of biological and phenotypic response to compound treatment. This model combines textual, tabular, and knowledge graph-derived representations of biological experiments to provide insights into molecular-level biological processes. We demonstrate that P3GPT has developed an intuition for the interactions between compounds, pathologies, and gene regulation in the context of multiple species and tissues. In these areas, it outperforms existing LLMs and we highlight its utility in diverse case studies. P3GPT is a general model that may be used as a target identification tool, aging clock, digital laboratory, and scientific assistant. The model is intended as a community resource available open source as well as via a Discord server.

Three novel strains of Gram-stain-negative, obligately anaerobic, spore-forming straight or slightly curved rods with pointed ends occurring singly or in pairs were isolated from the faeces of healthy human children. The strains were characterized by mesophilic fermentative metabolism and production of acetate, ethanol and H₂ as the end metabolic products. Strains ASD3451 and ASD5720^T were motile, fermented lactose and raffinose, and weakly fermented maltose. Strain ASD4241^T was non-motile and did not ferment the carbohydrates listed above but fermented starch. Strains ASD3451 and ASD5720^T shared average nucleotide identity higher than 98.5 % with each other, while ASD4241^T had only 88.5-89 % identity to them. Based on phylogenetic and chemotaxonomic analyses, we propose Diplocloster agilis gen. nov., sp. nov. (ASD5720^T=JCM 34353^T=VKM B-3497^T) and Diplocloster modestus sp. nov. (ASD4241^T=JCM 34351^T=VKM B-3498^T) within the family Lachnospiraceae .