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In this mini review, we discuss the relation between aggregation and bacterial dormancy, focusing on both persisters and VBNC cells. Understanding the link between protein aggregation and dormancy will not only provide insight into the fundamentals of bacterial survival, but could prove highly valuable in our future battle to fight them.The spatial and temporal coordination of protein transport is an essential cornerstone of the bacterial adaptation to different environmental conditions. By adjusting the protein composition of extra-cytosolic compartments, like the inner and outer membranes or the periplasmic space, protein transport mechanisms help shaping protein homeostasis in response to various metabolic cues. The universally conserved SecYEG translocon acts at the center of bacterial protein transport and mediates the translocation of newly synthesized proteins into and across the cytoplasmic membrane. The ability of the SecYEG translocon to transport an enormous variety of different substrates is in part determined by its ability to interact with multiple targeting factors, chaperones and accessory proteins. These interactions are crucial for the assisted passage of newly synthesized proteins from the cytosol into the different bacterial compartments. In this review, we summarize the current knowledge about SecYEG-mediated protein transport, primarily in the model organism Escherichia coli, and describe the dynamic interaction of the SecYEG translocon with its multiple partner proteins. We furthermore highlight how protein transport is regulated and explore recent developments in using the SecYEG translocon as an antimicrobial target.Extracellular RNAs (exRNAs) including abundant full length tRNAs and tRNA fragments (tRFs) have recently garnered attention as a promising source of biomarkers and a novel mediator in cell-to-cell communication in eukaryotes. Depending on the physiological state of cells, tRNAs/tRFs are released to the extracellular space either contained in extracellular vesicles (EVs) or free, through a mechanism that is largely unknown. In this perspective article, we propose that extracellular tRNAs (ex-tRNAs) and/or extracellular tRFs (ex-tRFs) are relevant paracrine signaling molecules whose activity depends on the mechanisms of release by source cells and capture by recipient cells. We speculate on how ex-tRNA/ex-tRFs orchestrate the effects in target cells, depending on the type of sequence and the mechanisms of uptake. We further propose that tRNA modifications may be playing important roles in ex-tRNA biology.Native cell extracts hold great promise for understanding the molecular structure of ordered biological systems at high resolution. This is because higher-order biomolecular interactions, dubbed as protein communities, may be retained in their (near-)native state, in contrast to extensively purifying or artificially overexpressing the proteins of interest. The distinct machine-learning approaches are applied to discover protein-protein interactions within cell extracts, reconstruct dedicated biological networks, and report on protein community members from various organisms. Their validation is also important, e.g., by the cross-linking mass spectrometry or cell biology methods. In addition, the cell extracts are amenable to structural analysis by cryo-electron microscopy (cryo-EM), but due to their inherent complexity, sorting structural signatures of protein communities derived by cryo-EM comprises a formidable task. The application of image-processing workflows inspired by machine-learning techniques would provide improvements in distinguishing structural signatures, correlating proteomic and network data to structural signatures and subsequently reconstructed cryo-EM maps, and, ultimately, characterizing unidentified protein communities at high resolution. In this review article, we summarize recent literature in detecting protein communities from native cell extracts and identify the remaining challenges and opportunities. We argue that the progress in, and the integration of, machine learning, cryo-EM, and complementary structural proteomics approaches would provide the basis for a multi-scale molecular description of protein communities within native cell extracts.MicroRNAs (miRNAs) are emerging as significant regulators of the tumorigenesis of gastric cancer (GC), and may be effective biomarkers for diagnosis, prognosis, and therapeutic targeting for GC. In this study, miR-653-5p was found to be significantly upregulated in GC tissues, serum, and cell lines and was strongly associated with poor prognosis in patients with GC. Furthermore, miR-653-5p promoted GC cell proliferation and metastasis in vivo and in vitro. Suppressor of cytokine signaling 6 (SOCS6) was directly targeted by miR-653-5p, and SOCS6 attenuated miR-653-5p-mediated GC cell growth, migration, and invasion. In addition, SOCS6-mediated inactivation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was also reversed by the administration of miR-653-5p. The findings from this study support a novel regulatory axis between miR-653-5p, SOCS6, and JAK2/STAT3 that may be a target for diagnosis and therapeutic intervention for GC.Carbonic anhydrases (CAs) are universal zinc ion containing metalloenzymes that play a pivotal role in various physiological processes. In this study, a CA I (designated as Hdh CA I) was isolated and characterized from the mantle tissue of Pacific abalone, Haliotis discus hannai. The full-length cDNA sequence of Hdh CA I was 1,417-bp in length, encoding a protein of 337 amino acids with molecular weight of 37.58 kDa. Hdh CA I sequence possessed a putative signal peptide of 22 amino acids and a CA catalytic function domain. The predicted protein shared 94 and 78% sequence identities with Haliotis gigantea and Haliotis tuberculata CA I, respectively. Results of phylogenetic analysis indicated that Hdh CA I was evolutionarily close to CA I of H. gigantea and H. tuberculata with high bootstrap values. Givinostat ic50 Significantly higher levels of Hdh CA I mRNA transcript were found in mantle than other examined tissues. In situ hybridization results showed strong hybridization signals in epithelial cells of the dorsal mantle pallial, an area known to synthesize and secrete proteins responsible for the nacreous layer formation of shell.
Homepage: https://www.selleckchem.com/products/ITF2357(Givinostat).html
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