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Human Pathology Mar 2023Clinical surveillance and follow-up of patients diagnosed with or at risk for urinary bladder cancers represent long-term, invasive, and costly processes for which... (Review)
Review
Clinical surveillance and follow-up of patients diagnosed with or at risk for urinary bladder cancers represent long-term, invasive, and costly processes for which supplemental biomarker information could help provide objective, personalized risk assessment. In particular, there are several precursors and possible precursors to urinary bladder cancer for which clinical behavior is heterogenous and interobserver variability in histopathologic diagnosis make it difficult to standardize management. This review seeks to highlight these precursor lesions from a diagnostic perspective (including flat urothelial lesions, papillary urothelial lesions, squamous lesions, and glandular lesions) and qualify known multiomic biomarkers that may help explain their behavior, predict patient risk, and acknowledge the nuance inherent to the question of whether these lesions are "benign" or "preneoplastic."
Topics: Humans; Urinary Bladder Neoplasms; Biomarkers; Urothelium
PubMed: 35716731
DOI: 10.1016/j.humpath.2022.06.006 -
Inorganic Chemistry Oct 2023Currently, two approaches dominate the large-scale production of MoS: liquid-phase exfoliation, referred to as the top-down approach, and bottom-up colloidal synthesis...
Currently, two approaches dominate the large-scale production of MoS: liquid-phase exfoliation, referred to as the top-down approach, and bottom-up colloidal synthesis from molecular precursors. Known colloidal synthesis approaches utilize toxic precursors. Here, an alternative green route for the bottom-up synthesis of MoS nanoflakes (NFs) is described. The NFs were synthesized by colloidal synthesis using [Mo(CHCOO)] and a series of sulfur (S)-precursors including thioacetamide (TAA), 3-mercaptopropionic acid (3-MPA), l-cysteine (L-CYS), mercaptosuccinic acid (MSA), 11-mercaptoundecanoic acid (MUA), 1-dodecanethiol (DDTH), and di--butyl disulfide (DTBD). While TAA, an S-precursor most commonly used for MoS NF preparation, is a known carcinogen, the other investigated S-precursors have low or no known toxicity. High-resolution scanning transmission electron microscopy (HR-STEM) and grazing incidence wide-angle X-ray scattering (GIWAXS) confirmed that in all cases, the syntheses yielded single-layer MoS NFs with lateral sizes smaller than 15 nm and a well-defined crystal structure. Electronic absorption and Raman spectra showed characteristic features associated with the MoS monolayers. The evolution of the absorption spectra of the growth solution during the syntheses reveals how the kinetics of the NF formation is affected by the S-precursor as well as the nature of the coordinating ligands.
PubMed: 37751900
DOI: 10.1021/acs.inorgchem.3c02420 -
ACS Omega Mar 2021Organoselenium compounds with perspective application as Se precursors for atomic layer deposition have been reviewed. The originally limited portfolio of available Se... (Review)
Review
Organoselenium compounds with perspective application as Se precursors for atomic layer deposition have been reviewed. The originally limited portfolio of available Se precursors such as HSe and diethyl(di)selenide has recently been extended by bis(trialkylsilyl)selenides, bis(trialkylstannyl)selenides, cyclic selenides, and tetrakis(,-dimethyldithiocarbamate)selenium. Their structural aspects, property tuning, fundamental properties, and preparations are discussed. It turned out that symmetric four- and six-membered cyclic silyl selenides possess well-balanced reactivity/stability, facile and cost-effective synthesis starting from inexpensive and readily available chlorosilanes, improved resistance toward air and moisture, easy handling, sufficient volatility, thermal resistance, and complete gas-to-solid phase exchange reaction with MoCl, affording MoSe nanostructures. These properties make them the most promising Se precursor developed for atomic layer deposition so far.
PubMed: 33748567
DOI: 10.1021/acsomega.1c00223 -
Current Opinion in Structural Biology Dec 2019The spliceosome executes eukaryotic precursor messenger RNA (pre-mRNA) splicing to remove noncoding introns through two sequential transesterification reactions,... (Review)
Review
The spliceosome executes eukaryotic precursor messenger RNA (pre-mRNA) splicing to remove noncoding introns through two sequential transesterification reactions, branching and exon ligation. The fidelity of this process is based on the recognition of the conserved sequences in the intron and dynamic compositional and structural rearrangement of this multi-megadalton machinery. Since atomic visualization of the splicing active site in an endogenous Schizosaccharomyces pombe spliceosome in 2015, high-resolution cryoelectron microscopy (cryo-EM) structures of other spliceosome intermediates began to uncover the molecular mechanism. Recent advances in the structural biology of the spliceosome make it clearer the mechanisms of its assembly, activation, disassembly and exon ligation. Together, these discrete structural images give rise to a molecular choreography of the spliceosome.
Topics: Cryoelectron Microscopy; Exons; Introns; Models, Molecular; Nucleic Acid Conformation; Protein Binding; Protein Conformation; RNA Precursors; RNA Splicing; Schizosaccharomyces; Spliceosomes; Structure-Activity Relationship
PubMed: 31476650
DOI: 10.1016/j.sbi.2019.07.010 -
Methods in Molecular Biology (Clifton,... 2023T lymphocytes (T cells) are essential components of the adaptive immune system; they serve multiple functions in responses to pathogens and to ensure immune homeostasis.... (Review)
Review
T lymphocytes (T cells) are essential components of the adaptive immune system; they serve multiple functions in responses to pathogens and to ensure immune homeostasis. Written for readers first entering this field of study, this chapter is a brief overview of the development of T cells in the thymus, from the entry of thymus-settling bone marrow-derived precursors to the egress of mature T cells. Surveyed topics include the differentiation and expansion of early precursors, the generation of the T cell antigen receptor repertoire, the selection of αβ T cell precursors, and their acquisition of functional competency.
Topics: Antigens; Cell Differentiation; Precursor Cells, T-Lymphoid; Receptors, Antigen, T-Cell; Receptors, Antigen, T-Cell, alpha-beta; Thymus Gland
PubMed: 36374448
DOI: 10.1007/978-1-0716-2740-2_1 -
The Journal of Nutrition Sep 2020A gluconeogenic precursor is a biochemical compound acted on by a gluconeogenic pathway enabling the net synthesis of glucose. Recognized gluconeogenic precursors in...
A gluconeogenic precursor is a biochemical compound acted on by a gluconeogenic pathway enabling the net synthesis of glucose. Recognized gluconeogenic precursors in fasting placental mammals include glycerol, lactate/pyruvate, certain amino acids, and odd-chain length fatty acids. Each of these precursors is capable of contributing net amounts of carbon to glucose synthesis via the tricarboxylic acid cycle (TCA cycle) because they are anaplerotic, that is, they are able to increase the pools of TCA cycle intermediates by the contribution of more carbon than is lost via carbon dioxide. The net synthesis of glucose from even-chain length fatty acids (ECFAs) in fasting placental mammals, via the TCA cycle alone, is not possible because equal amounts of carbon are lost via carbon dioxide as is contributed from fatty acid oxidation via acetyl-CoA. Therefore, ECFAs do not meet the criteria to be recognized as a gluconeogenic precursor via the TCA cycle alone. ECFAs are gluconeogenic precursors in organisms with a functioning glyoxylate cycle, which enables the net contribution of carbon to the intermediates of the TCA cycle from ECFAs and the net synthesis of glucose. The net conversion of ECFAs to glucose in fasting placental mammals via C3 metabolism of acetone may be a competent though inefficient metabolic path by which ECFA could be considered a gluconeogenic precursor. Defining a substrate as a gluconeogenic precursor requires careful articulation of the definition, organism, and physiologic conditions under consideration.
Topics: Acetyl Coenzyme A; Carbon; Citric Acid Cycle; Fatty Acids; Gluconeogenesis; Glucose; Glyoxylates; Humans; Oxidation-Reduction
PubMed: 32652033
DOI: 10.1093/jn/nxaa166 -
Frontiers in Bioengineering and... 2023Metabolic engineering strategies for terpenoid production have mainly focused on bottlenecks in the supply of precursor molecules and cytotoxicity to terpenoids. In... (Review)
Review
Metabolic engineering strategies for terpenoid production have mainly focused on bottlenecks in the supply of precursor molecules and cytotoxicity to terpenoids. In recent years, the strategies involving compartmentalization in eukaryotic cells has rapidly developed and have provided several advantages in the supply of precursors, cofactors and a suitable physiochemical environment for product storage. In this review, we provide a comprehensive analysis of organelle compartmentalization for terpenoid production, which can guide the rewiring of subcellular metabolism to make full use of precursors, reduce metabolite toxicity, as well as provide suitable storage capacity and environment. Additionally, the strategies that can enhance the efficiency of a relocated pathway by increasing the number and size of organelles, expanding the cell membrane and targeting metabolic pathways in several organelles are also discussed. Finally, the challenges and future perspectives of this approach for the terpenoid biosynthesis are also discussed.
PubMed: 36911190
DOI: 10.3389/fbioe.2023.1132244 -
The Journal of Biological Chemistry Jan 2024Developing quantitative models of substrate specificity for RNA processing enzymes is a key step toward understanding their biology and guiding applications in... (Review)
Review
Developing quantitative models of substrate specificity for RNA processing enzymes is a key step toward understanding their biology and guiding applications in biotechnology and biomedicine. Optimally, models to predict relative rate constants for alternative substrates should integrate an understanding of structures of the enzyme bound to "fast" and "slow" substrates, large datasets of rate constants for alternative substrates, and transcriptomic data identifying in vivo processing sites. Such data are either available or emerging for bacterial ribonucleoprotein RNase P a widespread and essential tRNA 5' processing endonuclease, thus making it a valuable model system for investigating principles of biological specificity. Indeed, the well-established structure and kinetics of bacterial RNase P enabled the development of high throughput measurements of rate constants for tRNA variants and provided the necessary framework for quantitative specificity modeling. Several studies document the importance of conformational changes in the precursor tRNA substrate as well as the RNA and protein subunits of bacterial RNase P during binding, although the functional roles and dynamics are still being resolved. Recently, results from cryo-EM studies of E. coli RNase P with alternative precursor tRNAs are revealing prospective mechanistic relationships between conformational changes and substrate specificity. Yet, extensive uncharted territory remains, including leveraging these advances for drug discovery, achieving a complete accounting of RNase P substrates, and understanding how the cellular context contributes to RNA processing specificity in vivo.
Topics: Escherichia coli; Nucleic Acid Conformation; Ribonuclease P; RNA Precursors; RNA, Bacterial; RNA, Transfer; Substrate Specificity; Bacterial Proteins; Protein Binding
PubMed: 38013087
DOI: 10.1016/j.jbc.2023.105498 -
Biochemical Society Transactions Nov 2021Many growth factors and cytokines are produced as larger precursors, containing pro-domains, that require proteolytic processing to release the bioactive ligand. These... (Review)
Review
Many growth factors and cytokines are produced as larger precursors, containing pro-domains, that require proteolytic processing to release the bioactive ligand. These pro-domains can be significantly larger than the mature domains and can play an active role in the regulation of the ligands. Mining the UniProt database, we identified almost one hundred human growth factors and cytokines with pro-domains. These are spread across several unrelated protein families and vary in both their size and composition. The precise role of each pro-domain varies significantly between the protein families. Typically they are critical for controlling bioactivity and protein localisation, and they facilitate diverse mechanisms of activation. Significant gaps in our understanding remain for pro-domain function - particularly their fate once the bioactive ligand has been released. Here we provide an overview of pro-domain roles in human growth factors and cytokines, their processing, regulation and activation, localisation as well as therapeutic potential.
Topics: Animals; Biomarkers; Cytokines; Drug Discovery; Humans; Intercellular Signaling Peptides and Proteins; Ligands; Protein Domains; Protein Precursors; Proteolysis; Signal Transduction
PubMed: 34495310
DOI: 10.1042/BST20200663 -
Clinical Gastroenterology and... Mar 2024The prevalence of precursor lesions for gastric cancer (GC) and the differential burden between countries of varying GC risk is not well-understood. We conducted a...
BACKGROUND & AIMS
The prevalence of precursor lesions for gastric cancer (GC) and the differential burden between countries of varying GC risk is not well-understood. We conducted a systematic review and meta-analysis to estimate the global prevalence of precursor lesions.
METHODS
We estimated the prevalence of atrophic gastritis (AG), gastric intestinal metaplasia (IM), and dysplasia in regions with low, medium, and high GC incidence. Because IM is an advanced manifestation of AG, we assessed the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. Prevalence was sub-stratified by Helicobacter pylori infection, symptomatology, and period (<2000, 2000-2010, and >2010).
RESULTS
Among the 582 articles that underwent full-text review, 166 studies met inclusion criteria. The global prevalence estimates of AG, IM, and dysplasia were 25.4%, 16.2%, and 2.0%, respectively, on the basis of 126 studies that reported the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. The prevalence of all precursor lesions was higher in high and medium compared with low GC incidence countries (P < .01). Prevalence of AG and IM was significantly higher among H pylori-infected individuals (P < .01) but not statistically different between symptomatic and asymptomatic individuals (P > .17). All precursors demonstrated a secular decrease in prevalence over time.
CONCLUSIONS
Gastric precursor lesions have differences in prevalence in regions with differential GC incidence and are associated with H pylori infection. Because of the substantial prevalence of precursor lesions in both symptomatic and asymptomatic individuals, symptomatic evaluation may not be sufficient to identify individuals at risk. These estimates provide important insights for tailoring GC prevention strategies.
PubMed: 38438000
DOI: 10.1016/j.cgh.2024.02.023