-
Biological Chemistry Oct 2023The ribosomal RNA precursor (pre-rRNA) comprises three of the four ribosomal RNAs and is synthesized by RNA polymerase (Pol) I. Here, we describe the mechanisms of Pol I... (Review)
Review
The ribosomal RNA precursor (pre-rRNA) comprises three of the four ribosomal RNAs and is synthesized by RNA polymerase (Pol) I. Here, we describe the mechanisms of Pol I transcription in human cells with a focus on recent insights gained from structure-function analyses. The comparison of Pol I-specific structural and functional features with those of other Pols and with the excessively studied yeast system distinguishes organism-specific from general traits. We explain the organization of the genomic rDNA loci in human cells, describe the Pol I transcription cycle regarding structural changes in the enzyme and the roles of human Pol I subunits, and depict human rDNA transcription factors and their function on a mechanistic level. We disentangle information gained by direct investigation from what had apparently been deduced from studies of the yeast enzymes. Finally, we provide information about how Pol I mutations may contribute to developmental diseases, and why Pol I is a target for new cancer treatment strategies, since increased rRNA synthesis was correlated with rapidly expanding cell populations.
Topics: Humans; RNA, Ribosomal; RNA Precursors; Saccharomyces cerevisiae; Transcription, Genetic; RNA Polymerase I; DNA, Ribosomal
PubMed: 37454246
DOI: 10.1515/hsz-2023-0214 -
Frontiers in Plant Science 2022is both a traditional herbal medicine and a plant of high ornamental and medicinal value. Alkaloids, especially terpenoid indole alkaloids (TIAs), with pharmacological...
is both a traditional herbal medicine and a plant of high ornamental and medicinal value. Alkaloids, especially terpenoid indole alkaloids (TIAs), with pharmacological activities are present in the tissues of . A number of genes involved in alkaloid biosynthetic pathways have been identified. However, the regulatory mechanisms underlying the precursor and methyl jasmonate (MeJA)-induced accumulation of alkaloids in are poorly understood. In this study, we collected protocorm-like bodies (PLBs) and treated them with TIA precursors (tryptophan and secologanin) and MeJA for 0 (T0), 4 (T4) and 24 h (T24); we also established control samples (C4 and C24). Then, we measured the total alkaloid content of the PLBs and performed transcriptome sequencing using the Illumina HiSeq 2,500 system. The total alkaloid content increased significantly after 4 h of treatment. Go and KEGG analysis suggested that genes from the TIA, isoquinoline alkaloid, tropane alkaloid and jasmonate (JA) biosynthetic pathways were significantly enriched. Weighted gene coexpression network analysis (WGCNA) uncovered brown module related to alkaloid content. Six and seven genes related to alkaloid and JA bisosynthetic pathways, respectively, might encode the key enzymes involved in alkaloid biosynthesis of . Moreover, 13 transcription factors (TFs), which mostly belong to AP2/ERF, WRKY, and MYB gene families, were predicted to regulate alkaloid biosynthesis. Our data provide insight for studying the regulatory mechanism underlying TIA precursor and MeJA-induced accumulation of three types of alkaloids in .
PubMed: 35937364
DOI: 10.3389/fpls.2022.941231 -
Journal of Labelled Compounds &... Jan 2022Copper-mediated nucleophilic radiofluorination using boronic precursors is a promising, general method to label aromatic compounds with [ F]fluoride. However, in various...
Copper-mediated nucleophilic radiofluorination using boronic precursors is a promising, general method to label aromatic compounds with [ F]fluoride. However, in various reports, large amounts of precursor (60 μmol) were needed to achieve high radiochemical conversions (RCCs), which is neither ideal nor practical for the preparation of F radiopharmaceuticals. To investigate this matter, we studied alcohol-enhanced Cu-mediated nucleophilic radiofluorination using a variety of model reactions in which we varied the concentration of [ F]fluoride (no carrier added or isotope diluted) and the amount of precursor, base, and Cu(OTF) (Py) . We found that lower amounts of precursors (e.g., 15 μmol) could be used and that the amount of base (e.g., K CO or KHCO ) played a critical and limiting role in the labeling reactions. Greater than one-equivalent of base and sufficient amounts of precursors and Cu(OTf) (Py) were required to achieve good to high RCCs. The RCCs were also dependent on the overall concentration of the labeling reactions, with low reaction volumes and high concentrations of reagents being preferred. Our findings will help to improve the design of radiolabeling protocols using alcohol-enhanced copper-mediated radiofluorination of boronic precursors for the preparation of F labeled radiopharmaceuticals and other radiohalogen-labeled compounds.
Topics: Copper; Fluorides; Fluorine Radioisotopes; Isotope Labeling; Radiochemistry; Radiopharmaceuticals
PubMed: 34617619
DOI: 10.1002/jlcr.3955 -
Water Research Apr 2023Both quantifiable and semi-quantifiable poly- and perfluoroalkyl substances (PFAS) were evaluated in the influent, effluent, and biosolids of 38 wastewater treatment...
Both quantifiable and semi-quantifiable poly- and perfluoroalkyl substances (PFAS) were evaluated in the influent, effluent, and biosolids of 38 wastewater treatment plants. PFAS were detected in all streams at all facilities. For the means of the sums of detected, quantifiable PFAS concentrations were 98 ± 28 ng/L, 80 ± 24 ng/L, and 160,000 ± 46,000 ng/kg (dry weight basis) in the influent, effluent, and biosolids (respectively). In the aqueous influent and effluent streams this quantifiable PFAS mass was typically associated with perfluoroalkyl acids (PFAAs). In contrast, quantifiable PFAS in the biosolids were primarily polyfluoroalkyl substances that potentially serve as precursors to the more recalcitrant PFAAs. Results of the total oxidizable precursor (TOP) assay on select influent and effluent samples showed that semi-quantified (or, unidentified) precursors accounted for a substantial portion (21 to 88%) of the fluorine mass compared to that associated with quantified PFAS, and that this fluorine precursor mass was not appreciably transformed to perfluoroalkyl acids within the WWTPs, as influent and effluent precursor concentrations via the TOP assay were statistically identical. Evaluation of semi-quantified PFAS, consistent with results of the TOP assay, showed the presence of several classes of precursors in the influent, effluent, and biosolids; perfluorophosphonic acids (PFPAs) and fluorotelomer phosphate diesters (di-PAPs) occurred in 100 and 92% of biosolid samples, respectively. Analysis of mass flows showed that, for both quantified (on a fluorine mass basis) and semi-quantified PFAS, the majority of PFAS exited WWTPs through the aqueous effluent compared to the biosolids stream. Overall, these results highlight the importance of semi-quantified PFAS precursors in WWTPs, and the need to further understand the impacts of their ultimate fate in the environment.
Topics: Water Pollutants, Chemical; Biosolids; Fluorine; Fluorocarbons; Water Purification; Water
PubMed: 36801573
DOI: 10.1016/j.watres.2023.119724 -
Membranes Jun 2021Carbon molecular sieve (CMS) membranes have been developed to replace or support energy-intensive cryogenic distillation for olefin/paraffin separation. Olefin and... (Review)
Review
Carbon molecular sieve (CMS) membranes have been developed to replace or support energy-intensive cryogenic distillation for olefin/paraffin separation. Olefin and paraffin have similar molecular properties, but can be separated effectively by a CMS membrane with a rigid, slit-like pore structure. A variety of polymer precursors can give rise to different outcomes in terms of the structure and performance of CMS membranes. Herein, for olefin/paraffin separation, the CMS membranes derived from a number of polymer precursors (such as polyimides, phenolic resin, and polymers of intrinsic microporosity, PIM) are introduced, and olefin/paraffin separation properties of those membranes are summarized. The effects from incorporation of inorganic materials into polymer precursors and from a pyrolysis process on the properties of CMS membranes are also reviewed. Finally, the prospects and future directions of CMS membranes for olefin/paraffin separation and aging issues are discussed.
PubMed: 34209477
DOI: 10.3390/membranes11070482 -
Critical Reviews in Food Science and... Jul 2023Natural animal-based flavors have great appeal to consumers and have broad applications in the food industry. In this review, we summarized findings related to bacon and... (Review)
Review
Natural animal-based flavors have great appeal to consumers and have broad applications in the food industry. In this review, we summarized findings related to bacon and Cheddar cheese flavors' components and their precursors, reaction mechanisms, influential factors, and characterization methods. The results show that free sugars, free amino acids, peptides, vitamins, lipids, and nitrites are precursors to bacon flavor. The conditions governing the formation of bacon flavor are thermally dependent, which facilitates the use of thermal food processing to generate such a flavor. For Cheddar cheese flavor, milk ingredients such as lactose, citrate, fat, and casein are reported as precursors. The optimum conditions to generate Cheddar cheese flavor from precursors are quite strict, which limits its application in food processing. As an alternative, it is more practical to generate Cheddar cheese flavor by combining key aroma compounds using thermal food processing. This review provides the food industry the comprehensive information about the generation of bacon and Cheddar cheese flavors using precursor molecules.
PubMed: 37431669
DOI: 10.1080/10408398.2023.2230497 -
PLoS Computational Biology Oct 2019MicroRNAs are conserved, endogenous small RNAs with critical post-transcriptional regulatory functions throughout eukaryota, including prominent roles in development and...
MicroRNAs are conserved, endogenous small RNAs with critical post-transcriptional regulatory functions throughout eukaryota, including prominent roles in development and disease. Despite much effort, microRNA annotations still contain errors and are incomplete due especially to challenges related to identifying valid miRs that have small numbers of reads, to properly locating hairpin precursors and to balancing precision and recall. Here, we present miRWoods, which solves these challenges using a duplex-focused precursor detection method and stacked random forests with specialized layers to detect mature and precursor microRNAs, and has been tuned to optimize the harmonic mean of precision and recall. We trained and tuned our discovery pipeline on data sets from the well-annotated human genome, and evaluated its performance on data from mouse. Compared to existing approaches, miRWoods better identifies precursor spans, and can balance sensitivity and specificity for an overall greater prediction accuracy, recalling an average of 10% more annotated microRNAs, and correctly predicts substantially more microRNAs with only one read. We apply this method to the under-annotated genomes of Felis catus (domestic cat) and Bos taurus (cow). We identified hundreds of novel microRNAs in small RNA sequencing data sets from muscle and skin from cat, from 10 tissues from cow and also from human and mouse cells. Our novel predictions include a microRNA in an intron of tyrosine kinase 2 (TYK2) that is present in both cat and cow, as well as a family of mirtrons with two instances in the human genome. Our predictions support a more expanded miR-2284 family in the bovine genome, a larger mir-548 family in the human genome, and a larger let-7 family in the feline genome.
Topics: Animals; Base Sequence; Cats; Cattle; Computational Biology; Female; Gene Expression Regulation; Genome; High-Throughput Nucleotide Sequencing; Humans; Male; MicroRNAs; RNA Precursors; Sequence Analysis, RNA
PubMed: 31596843
DOI: 10.1371/journal.pcbi.1007309 -
Chemistry of Materials : a Publication... Sep 2022The synthesis of iron oxide nanoparticles with control over size and shape has long been an area of research, with iron oleate being arguably the most successful...
The synthesis of iron oxide nanoparticles with control over size and shape has long been an area of research, with iron oleate being arguably the most successful precursor. Issues with reproducibility and versatility in iron oleate-based syntheses remain, however, in large part due to the mutable nature of its structure and stoichiometry. In this work, we characterize two new forms of iron oleate precursor that can be isolated in large quantities, show long-term stability, and have well-defined stoichiometry, leading to reproducible and predictable reactivity. Synthesis with these precursors is shown to produce iron oxide nanoparticles in a tunable size range of 4-16 nm with low size dispersity and properties consistent with magnetite in the superparamagnetic size regime.
PubMed: 36117881
DOI: 10.1021/acs.chemmater.2c02046 -
Organic Letters Mar 2022The preparation of 2,2,2-trifluoroacetaldehyde -(aryl)oxime, a previously inaccessible precursor of trifluoroacetonitrile, via reaction of hydroxylamine and...
The preparation of 2,2,2-trifluoroacetaldehyde -(aryl)oxime, a previously inaccessible precursor of trifluoroacetonitrile, via reaction of hydroxylamine and trifluoroacetaldehyde hydrate is reported. This precursor released CFCN in quantitative yield under mildly basic conditions. The precursor was successfully used in the synthesis of trifluoromethylated oxadiazoles. The facile, cost-effective, scalable, and recyclable procedure makes these trifluoroacetonitrile precursors generally applicable.
Topics: Acetaldehyde; Oxadiazoles; Oximes
PubMed: 35266394
DOI: 10.1021/acs.orglett.2c00637 -
Frontiers in Immunology 2019NK cells are generated from hematopoietic stem cells (HSC) residing in the bone marrow (BM), similar to other blood cells. Development toward mature NK cells occurs... (Review)
Review
NK cells are generated from hematopoietic stem cells (HSC) residing in the bone marrow (BM), similar to other blood cells. Development toward mature NK cells occurs largely outside the BM through travel of CD34+ and other progenitor intermediates toward secondary lymphoid organs. The BM harbors multipotent CD34+ common lymphoid progenitors (CLPs) that generate T, B, NK, and Dendritic Cells and are devoid of erythroid, myeloid, and megakaryocytic potential. Over recent years, there has been a quest for single-lineage progenitors predominantly with the objective of manipulation and intervention in mind, which has led to the identification of unipotent NK cell progenitors devoid of other lymphoid lineage potential. Research efforts for the study of lymphopoiesis have almost exclusively concentrated on healthy donor tissues and on repopulation/transplant models. This has led to the widely accepted assumption that lymphopoiesis during disease states reflects the findings of these models. However, compelling evidences in animal models show that inflammation plays a fundamental role in the regulation of HSC maturation and release in the BM niches through several mechanisms including modulation of the CXCL12-CXCR4 expression. Indeed, recent findings during systemic inflammation in patients provide evidence that a so-far overlooked CLP exists in the BM (LinCD34DNAM-1CXCR4) and that it overwhelmingly exits the BM during systemic inflammation. These "inflammatory" precursors have a developmental trajectory toward surprisingly functional NK and T cells as reviewed here and mirror the steady state maintenance of the NK cell pool by CD34DNAM-1CXCR4 precursors. Our understanding of NK cell precursor development may benefit from including a distinct "inflammatory" progenitor modeling of lymphoid precursors, allowing rapid deployment of specialized LinCD34DNAM-1CXCR4 -derived resources from the BM.
Topics: Animals; Biomarkers; Bone Marrow Cells; Cell Differentiation; Disease Susceptibility; Homeostasis; Humans; Immunophenotyping; Inflammation; Lymphoid Progenitor Cells; Stem Cell Niche
PubMed: 31555276
DOI: 10.3389/fimmu.2019.02045