Salmonella spp is a major foodborne pathogen with a wide variety of serovars associated with human cases and food sources Nevertheless, in Europe a panel of ten serovars is responsible for up to 80 of confirmed human cases Clustering studies by single nucleotide polymorphism SNP core-genome phylogenetic analysis of outbreaks due to these major serovars are simplified by the availability of many complete genomes in the free access databases This is not the case for outbreaks due to less common serovars, such as Welikade, for which no reference genomes are available In this study, we propose a method to solve this problem We propose to perform a core genome MLST cgMLST analysis based on hierarchical clustering using the free-access EnteroBase to select the most suitable genome to use as a reference for SNP phylogenetic analysis In this study, we applied this protocol to a retrospective analysis of a Salmonella enterica serovar Welikade S Welikade foodborne outbreak that occurred in France in 20described serovar and enriches public genome databases with 42 genomes from human and non-human S Welikade strains, including the isolate collected in 1956 in Sri Lanka, which gave the name to this serovar This is the first genomic analysis of an outbreak due to S Welikade described to dateThe Wnt pathway is central to a host of developmental and disease-related processes The remarkable conservation of this intercellular signaling cascade throughout metazoan lineages indicates that it coevolved with multicellularity to regulate the generation and spatial arrangement of distinct cell types By regulating cell fate specification, mitotic activity, and cell polarity, Wnt signaling orchestrates development and tissue homeostasis, and its dysregulation is implicated in developmental defects, cancer, and degenerative disorders We review advances in our understanding of this key pathway, from Wnt protein production and secretion to relay of the signal in the cytoplasm of the receiving cell We discuss the evolutionary history of this pathway as well as endogenous and synthetic modulators of its activity Finally, we highlight remaining gaps in our knowledge of Wnt signal transduction and avenues for future researchMetals are essential components in life processes and participate in many important biological processes Dysregulation of metal homeostasis is correlated with many diseases Metals are also frequently incorporated into diagnosis and therapeutics Understanding of metal homeostasis under pathophysiological conditions and the molecular mechanisms of action of metallodrugs in biological systems has positive impacts on human health As an emerging interdisciplinary area of research, metalloproteomics involves investigating metal-protein interactions in biological systems at a proteome-wide scale, has received growing attention, and has been implemented into metal-related research In this review, we summarize the recent advances in metalloproteomics methodologies and applications We also highlight emerging single-cell metalloproteomics, including time-resolved inductively coupled plasma mass spectrometry, mass cytometry, and secondary ion mass spectrometry Finally, we discuss future perspectives in metalloproteomics, aiming to attract more original research to develop more advanced methodologies, which could be utilized rapidly by biochemists or biologists to expand our knowledge of how metal functions in biology and medicineSubcellular compartmentalization is a defining feature of all cells In prokaryotes, compartmentalization is generally achieved via protein-based strategies The two main classes of microbial protein compartments are bacterial microcompartments and encapsulin nanocompartments Encapsulins self-assemble into proteinaceous shells with diameters between 24 and 42 nm and are defined by the viral HK97-fold of their shell protein Encapsulins have the ability to encapsulate dedicated cargo proteins, including ferritin-like proteins, peroxidases, and desulfurases Encapsulation is mediated by targeting sequences present in all cargo proteins Encapsulins are found in many bacterial and archaeal phyla and have been suggested to play roles in iron storage, stress resistance, sulfur metabolism, and natural product biosynthesis  https//wwwselleckchemcom/products/PHA-665752html  Phylogenetic analyses indicate that they share a common ancestor with viral capsid proteins Many pathogens encode encapsulins, and recent evidence suggests that they may contribute toward pathogenicity The existing information on encapsulin structure, biochemistry, biological function, and biomedical relevance is reviewed hereCovalent DNA-protein crosslinks DPCs are pervasive DNA lesions that interfere with essential chromatin processes such as transcription or replication This review strives to provide an overview of the sources and principles of cellular DPC formation DPCs are caused by endogenous reactive metabolites and various chemotherapeutic agents However, in certain conditions DPCs also arise physiologically in cells We discuss the cellular mechanisms resolving these threats to genomic integrity Detection and repair of DPCs require not only the action of canonical DNA repair pathways but also the activity of specialized proteolytic enzymes-including proteases of the SPRTN/Wss1 family-to degrade the crosslinked protein Loss of DPC repair capacity has dramatic consequences, ranging from genome instability in yeast and worms to cancer predisposition and premature aging in mice and humansGene regulation arises out of dynamic competition between nucleosomes, transcription factors, and other chromatin proteins for the opportunity to bind genomic DNA The timescales of nucleosome assembly and binding of factors to DNA determine the outcomes of this competition at any given locus Here, we review how these properties of chromatin proteins and the interplay between the dynamics of different factors are critical for gene regulation We discuss how molecular structures of large chromatin-associated complexes, kinetic measurements, and high resolution mapping of protein-DNA complexes in vivo set the boundary conditions for chromatin dynamics, leading to models of how the steady state behaviors of regulatory elements ariseDEAD-box ATPases constitute a very large protein family present in all cells, often in great abundance From bacteria to humans, they play critical roles in many aspects of RNA metabolism, and due to their widespread importance in RNA biology, they have been characterized in great detail at both the structural and biochemical levels DEAD-box proteins function as RNA-dependent ATPases that can unwind short duplexes of RNA, remodel ribonucleoprotein RNP complexes, or act as clamps to promote RNP assembly Yet, it often remains enigmatic how individual DEAD-box proteins mechanistically contribute to specific RNA-processing steps Here, we review the role of DEAD-box ATPases in the regulation of gene expression and propose that one common function of these enzymes is in the regulation of liquid-liquid phase separation of RNP condensatesMitogen-activated protein kinase MAPK-activated protein kinases MAPKAPKs are defined by their exclusive activation by MAPKs They can be activated by classical and atypical MAPKs that have been stimulated by mitogens and various stresses Genetic deletions of MAPKAPKs and availability of highly specific small-molecule inhibitors have continuously increased our functional understanding of these kinases MAPKAPKs cooperate in the regulation of gene expression at the level of transcription; RNA processing, export, and stability; and protein synthesis The diversity of stimuli for MAPK activation, the crosstalk between the different MAPKs and MAPKAPKs, and the specific substrate pattern of MAPKAPKs orchestrate immediate-early and inflammatory responses in space and time and ensure proper control of cell growth, differentiation, and cell behavior Hence, MAPKAPKs are promising targets for cancer therapy and treatments for conditions of acute and chronic inflammation, such as cytokine storms and rheumatoid arthritisThe brain, as one of the most lipid-rich organs, heavily relies on lipid transport and distribution to maintain homeostasis and neuronal function Lipid transport mediated by lipoprotein particles, which are complex structures composed of apolipoproteins and lipids, has been thoroughly characterized in the periphery Although lipoproteins in the central nervous system CNS were reported over half a century ago, the identification of APOE4 as the strongest genetic risk factor for Alzheimer's disease has accelerated investigation of the biology and pathobiology of lipoproteins in the CNS This review provides an overview of the different components of lipoprotein particles, in particular apolipoproteins, and their involvements in both physiological functions and pathological mechanisms in the CNSThe past decade has seen impressive advances in understanding the biosynthesis of ribosomally synthesized and posttranslationally modified peptides RiPPs One of the most common modifications found in these natural products is macrocyclization, a strategy also used by medicinal chemists to improve metabolic stability and target affinity and specificity Another tool of the peptide chemist, modification of the amides in a peptide backbone, has also been observed in RiPPs This review discusses the molecular mechanisms of biosynthesis of a subset of macrocyclic RiPP families, chosen because of the unusual biochemistry involved the five classes of lanthipeptides thioether cyclization by Michael-type addition, sactipeptides and ranthipeptides thioether cyclization by radical chemistry, thiopeptides cyclization by [4+2] cycloaddition, and streptide cyclization by radical C-C bond formation In addition, the mechanisms of backbone amide methylation, backbone epimerization, and backbone thioamide formation are discussed, as well as an unusual route to small molecules by posttranslational modification
  The aim of this study was to simultaneously analyze estrogen quinone-derived adducts, including 17β-estradiol-2,3-quinone E
  -2,3-Q and 17β-estradiol-3,4-quinone E
  -3,4-Q, in human albumin Alb and hemoglobin Hb derived from breast cancer patients with five-year postoperative treatment without recurrence in Taiwan and to evaluate the treatment-related effects on the production of these adducts
 
  Cohort
  Blood samples derived from breast cancer 5-year survivors without recurrence were collected Albumin and hemoglobin adducts of E
  -3,4-Q and E
  -2,3-Q were analyzed to evaluate the degree of disposition of estrogen to quinones and to compare these adduct levels with those in patients before treatment
 
  All data are expressed as mean ± standard deviation of three determinations We used Student's 
  -test to examine subgroups Data were transformed to the natural logarithm and tested for normal distribution for parametric analyses Linear correlations were investigated between individual adduct leveombination of treatment-related effects and environmental factors may modulate estrogen homeostasis and diminish the production of estrogen quinones in breast cancer patients