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Environmental Science & Technology Nov 2022To unravel the complexity of per- and polyfluoroalkyl substances (PFAS) in products and environmental samples, sum parameters that provide relevant information on...
To unravel the complexity of per- and polyfluoroalkyl substances (PFAS) in products and environmental samples, sum parameters that provide relevant information on chemical characteristics are necessary since not all PFAS can be captured by target analysis in case of missing reference standards or if they are not extractable or amenable to the analytical method. Therefore, we evaluated photocatalysis (UV/TiO) as a further total oxidizable precursor approach (PhotoTOP) to characterize perfluoroalkyl acid precursors via their conversion to perfluoroalkyl carboxylic acids (PFCAs). Photocatalysis has the advantage that no salts are needed, allowing direct injection with liquid chromatography-mass spectrometry without time-consuming and potentially discriminating sample cleanup. OH radicals were monitored with OH probes to determine the reactivity. For eight different precursors (diPAPs, FTSAs, FTCAs, -EtFOSAA, PFOSA), mass balance was achieved within 4 h of oxidation, and also, in the presence of matrix, complete conversion was possible. The PhotoTOP was able to predict the precursor chain length of known and here newly identified precursors qualitatively when applied to two PFAS-coated paper samples and technical PFAS mixtures. The length of the perfluorinated carbon chain (n) was mostly conserved in the form of PFCAs (n-1) with only minor fractions of shorter-chain PFCAs. Finally, an unknown fabric sample and a polymer mixture (no PFAS detectable in extracts) were oxidized, and the generated PFCAs indicated the occurrence of side-chain fluorinated polymers.
Topics: Environmental Monitoring; Fluorocarbons; Carboxylic Acids; Water Pollutants, Chemical
PubMed: 36305720
DOI: 10.1021/acs.est.2c05652 -
Journal of Hepato-biliary-pancreatic... Jul 2023To clarify the pathological significance of two precursors (high-grade biliary intraepithelial neoplasm [BilIN] and intraductal papillary neoplasm of bile duct [IPNB])...
BACKGROUND
To clarify the pathological significance of two precursors (high-grade biliary intraepithelial neoplasm [BilIN] and intraductal papillary neoplasm of bile duct [IPNB]) in cholangiocarcinomas (CCAs).
METHODS
Ninety-one cases of CCA (47 distal CCAs [dCCAs], 31 perihilar CCAs [pCCAs] and 13 intrahepatic CCAs of large duct type [LD-iCCAs]) were examined for their association with precursors. Neoplastic intraepithelial lesions without underlying infiltrating carcinoma in the surrounding mucosa of CCAs were considered to reflect high-grade BilIN. High-grade BilIN and IPNB were subdivided into gastric, biliary, intestinal and oncocytic subtypes, while CCAs were subdivided into gastrobiliary, intestinal and oncocytic subtypes. The postoperative overall survival (OS) was examined.
RESULTS
Fifty-four and 8 of 91 CCAs were associated with high-grade BilIN and IPNB, respectively, while these precursors were unidentifiable in the remaining CCAs. A majority of CCAs were of the gastrobiliary subtype, while the intestinal subtype was occasionally detected, and the oncocytic subtype was rare. CCAs with high-grade BilIN showed a similar postoperative OS to CCAs without precursors, while CCAs with IPNB showed a favorable postoperative OS compared to CCAs without precursors.
CONCLUSIONS
CCAs were frequently associated with precursors; high-grade BilIN may be a major precursor and IPNB a minor one. CCAs with IPNB showed a favorable postoperative OS compared to CCAs with high-grade BilIN.
Topics: Humans; Bile Ducts, Intrahepatic; Bile Duct Neoplasms; Cholangiocarcinoma; Bile Ducts; Carcinoma in Situ; Bile Pigments
PubMed: 36707055
DOI: 10.1002/jhbp.1308 -
The American Journal of Surgical... Aug 2023Recently, the World Health Organization (WHO) recognized the existence of human papillomavirus (HPV)-independent invasive cervical squamous cell carcinoma (SCC), but...
Recently, the World Health Organization (WHO) recognized the existence of human papillomavirus (HPV)-independent invasive cervical squamous cell carcinoma (SCC), but HPV-independent precursor lesions were not included due to the lack of description of this rare entity. We present the histologic spectrum of highly differentiated squamous HPV-negative and p16 ink4a -negative precursor lesions adjacent to and/or preceding invasive HPV-negative cervical SCC in 3 patients. The histologic features resembled those described for vulvar HPV-negative precursor lesions. One precursor featured a proliferation of atypical basal keratinocytes with mitotic activity, premature squamatization in elongated epithelial rete, and mostly regular superficial squamous differentiation with TP53 mutation and immunohistochemical p53 overexpression termed differentiated cervical intraepithelial neoplasia (d-CIN). The other 2 precursors included verruciform acanthosis with plump rete, minimal atypia, and an EGFR mutation that resembled vulvar acanthosis with altered differentiation, and an exophytic papillary proliferation with a PIK3CA mutation resembling the differentiated exophytic vulvar intraepithelial lesion. Two precursors that preceded the invasive SCC harbored an additional pathogenic SMARCB1 mutation. The cytologic smears of d-CIN revealed 3-dimensional branched basaloid tubular structures and eosinophilic squamous cell clusters mimicking the histologic features. In conclusion, highly differentiated cervical HPV-negative precursors are characteristic intraepithelial squamous lesions with somatic mutations that resemble those described in vulvar HPV-independent carcinogenesis. For optimal reproducibility, we propose a simplistic classification of these HPV-negative cervical precursors in TP53 -mutated d-CIN and p53 wild-type verruciform intraepithelial neoplasia.
Topics: Female; Humans; Tumor Suppressor Protein p53; Papillomavirus Infections; Reproducibility of Results; Vulvar Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; Papillomaviridae; Uterine Cervical Dysplasia; Cyclin-Dependent Kinase Inhibitor p16
PubMed: 37283469
DOI: 10.1097/PAS.0000000000002067 -
The New Phytologist Jan 2021The gaseous plant hormone ethylene is produced by a fairly simple two-step biosynthesis route. Despite this pathway's simplicity, recent molecular and genetic studies... (Review)
Review
The gaseous plant hormone ethylene is produced by a fairly simple two-step biosynthesis route. Despite this pathway's simplicity, recent molecular and genetic studies have revealed that the regulation of ethylene biosynthesis is far more complex and occurs at different layers. Ethylene production is intimately linked with the homeostasis of its general precursor S-adenosyl-l-methionine (SAM), which experiences transcriptional and posttranslational control of its synthesising enzymes (SAM synthetase), as well as the metabolic flux through the adjacent Yang cycle. Ethylene biosynthesis continues from SAM by two dedicated enzymes: 1-aminocyclopropane-1-carboxylic (ACC) synthase (ACS) and ACC oxidase (ACO). Although the transcriptional dynamics of ACS and ACO have been well documented, the first transcription factors that control ACS and ACO expression have only recently been discovered. Both ACS and ACO display a type-specific posttranslational regulation that controls protein stability and activity. The nonproteinogenic amino acid ACC also shows a tight level of control through conjugation and translocation. Different players in ACC conjugation and transport have been identified over the years, however their molecular regulation and biological significance is unclear, yet relevant, as ACC can also signal independently of ethylene. In this review, we bring together historical reports and the latest findings on the complex regulation of the ethylene biosynthesis pathway in plants.
Topics: Amino Acid Oxidoreductases; Ethylenes; Gene Expression Regulation, Plant; Lyases; Plants
PubMed: 32790878
DOI: 10.1111/nph.16873 -
Current Protein & Peptide Science 2023With the advent of cancer diagnostics and therapeutics, circular RNAs (circRNAs) are swiftly becoming one of the significant regulators of gene expression and cellular... (Review)
Review
BACKGROUND
With the advent of cancer diagnostics and therapeutics, circular RNAs (circRNAs) are swiftly becoming one of the significant regulators of gene expression and cellular functions. A plethora of multiple molecular mechanisms has been observed to elicit their influence.
OBJECTIVE
Circular RNAs (circRNAs) are a distinct category of endogenous noncoding RNAs designed as a result of exon back splicing events in precursor's mRNAs (pre-mRNAs) and are widely distributed in the transcriptome of eukaryotic cells.
METHODS
Although the role of circRNAs is still in its infancy, they serve as microRNA sponges, protein scaffolds, and modulators of transcription and splicing and occasionally as templates for the production of peptides.
RESULTS
It is well known that abnormal circRNA expression is prevalent in malignancies and has been linked to a number of pathophysiological aspects of cancer. This extensively anomalous expression assists in cellular proliferation and growth, sustaining cellular invasiveness and bypassing cellular senescence and death, thus advocating their promise to serve as both clinical biomarkers and therapeutic targets.
CONCLUSION
An overview of the recent status of circRNA will aid in the identification of new biomarkers, therapeutic targets, and their prospect in the diagnosis and therapy of disease. In this review article, we discuss the functional mechanisms of circRNAs, their biomarker potential in disease diagnosis and prognosis, therapeutic approaches, and the associated limitations.
Topics: Humans; RNA, Circular; Neoplasms; MicroRNAs; Biomarkers; RNA Splicing
PubMed: 36635927
DOI: 10.2174/1389203724666230111113715 -
International Journal of Molecular... Mar 2021Protein post-translational modifications (PTMs) play key roles in eukaryotes since they finely regulate numerous mechanisms used to diversify the protein functions and... (Review)
Review
Protein post-translational modifications (PTMs) play key roles in eukaryotes since they finely regulate numerous mechanisms used to diversify the protein functions and to modulate their signaling networks. Besides, these chemical modifications also take part in the viral hijacking of the host, and also contribute to the cellular response to viral infections. All domains of the human immunodeficiency virus type 1 (HIV-1) Gag precursor of 55-kDa (Pr55), which is the central actor for viral RNA specific recruitment and genome packaging, are post-translationally modified. In this review, we summarize the current knowledge about HIV-1 Pr55 PTMs such as myristoylation, phosphorylation, ubiquitination, sumoylation, methylation, and ISGylation in order to figure out how these modifications affect the precursor functions and viral replication. Indeed, in HIV-1, PTMs regulate the precursor trafficking between cell compartments and its anchoring at the plasma membrane, where viral assembly occurs. Interestingly, PTMs also allow Pr55 to hijack the cell machinery to achieve viral budding as they drive recognition between viral proteins or cellular components such as the ESCRT machinery. Finally, we will describe and compare PTMs of several other retroviral Gag proteins to give a global overview of their role in the retroviral life cycle.
Topics: Cell Membrane; Endosomal Sorting Complexes Required for Transport; HIV-1; Humans; Protein Precursors; Protein Processing, Post-Translational; RNA, Viral; Virus Assembly; Virus Replication; gag Gene Products, Human Immunodeficiency Virus
PubMed: 33799890
DOI: 10.3390/ijms22062871 -
Materials Horizons Apr 2023With the rapid development of integrated electronics and optoelectronics, methods for the scalable industrial-scale growth of two-dimensional (2D) transition metal... (Review)
Review
With the rapid development of integrated electronics and optoelectronics, methods for the scalable industrial-scale growth of two-dimensional (2D) transition metal dichalcogenide (TMD) materials have become a hot research topic. However, the control of gas distribution of solid precursors in common chemical vapor deposition (CVD) is still a challenge, resulting in the growth of 2D TMDs strongly influenced by the location of the substrate from the precursor powder. In contrast, liquid-precursor-intermediated growth not only avoids the use of solid powders but also enables the uniform distribution of precursors on the substrate through spin-coating, which is much more favorable for the synthesis of wafer-scale TMDs. Moreover, the spin-coating process based on liquid precursors can control the thickness of the spin-coated films by regulating the solution concentration and spin-coating speed. Herein, this review focuses on the recent progress in the synthesis of 2D TMDs based on liquid-precursor-intermediated CVD (LPI-CVD) growth. Firstly, the different assisted treatments based on LPI-CVD strategies for monolayer 2D TMDs are introduced. Then, the progress in the regulation of the different physical properties of monolayer 2D TMDs by substitution of the transition metal and their corresponding heterostructures based on LPI-CVD growth are summarized. Finally, the challenges and perspectives of 2D TMDs based on the LPI-CVD method are discussed.
PubMed: 36628937
DOI: 10.1039/d2mh01207c -
International Journal of Molecular... Dec 2021With few exceptions, proteins that constitute the proteome of mitochondria originate outside of this organelle in precursor forms. Such protein precursors follow... (Review)
Review
With few exceptions, proteins that constitute the proteome of mitochondria originate outside of this organelle in precursor forms. Such protein precursors follow dedicated transportation paths to reach specific parts of mitochondria, where they complete their maturation and perform their functions. Mitochondrial precursor targeting and import pathways are essential to maintain proper mitochondrial function and cell survival, thus are tightly controlled at each stage. Mechanisms that sustain protein homeostasis of the cytosol play a vital role in the quality control of proteins targeted to the organelle. Starting from their synthesis, precursors are constantly chaperoned and guided to reduce the risk of premature folding, erroneous interactions, or protein damage. The ubiquitin-proteasome system provides proteolytic control that is not restricted to defective proteins but also regulates the supply of precursors to the organelle. Recent discoveries provide evidence that stress caused by the mislocalization of mitochondrial proteins may contribute to disease development. Precursors are not only subject to regulation but also modulate cytosolic machinery. Here we provide an overview of the cellular pathways that are involved in precursor maintenance and guidance at the early cytosolic stages of mitochondrial biogenesis. Moreover, we follow the circumstances in which mitochondrial protein import deregulation disturbs the cellular balance, carefully looking for rescue paths that can restore proteostasis.
Topics: Cell Survival; Cytosol; Humans; Mitochondria; Mitochondrial Proteins; Organelle Biogenesis; Protein Precursors; Protein Transport
PubMed: 35008433
DOI: 10.3390/ijms23010007 -
Foods (Basel, Switzerland) Jul 2022Volatile polyfunctional thiol compounds, particularly 3-sulfanylhexan-1-ol (3SH) and 3-sulfanylhexyl acetate (3SHA), are key odorants contributing to the aroma profile... (Review)
Review
Volatile polyfunctional thiol compounds, particularly 3-sulfanylhexan-1-ol (3SH) and 3-sulfanylhexyl acetate (3SHA), are key odorants contributing to the aroma profile of many wine styles, generally imparting tropical grapefruit and passionfruit aromas. 3SH and 3SHA are present in negligible concentrations in the grape berry, juice, and must, suggesting that they are released from non-volatile precursors present in the grape. The exploration of the nature and biogenesis of these precursors to 3SH and 3SHA has proven important for the elucidation of polyfunctional thiol biogenesis during alcoholic fermentation. The development and validation of appropriate analytical techniques for the analysis of 3SH precursors in enological matrices have been extensive, and this review explores the analysis and discovery of these precursor compounds. The development of analytical methods to analyze 3SH precursors, from the selection of the analytical instrument, sample preparation, and methods for standardization, will first be discussed, before highlighting how these techniques have been used in the elucidation of the biogenesis of 3SH and 3SHA in grape wines. Lastly, the future of thiol precursor analysis will be considered, with the development of new methods that greatly reduce the sample preparation time and enable multiple precursors, and the thiols themselves, to be quantitated using a single method.
PubMed: 35885295
DOI: 10.3390/foods11142050 -
Nature Communications Sep 2021Nuclear-encoded mitochondrial proteins destined for the matrix have to be transported across two membranes. The TOM and TIM23 complexes facilitate the transport of...
Nuclear-encoded mitochondrial proteins destined for the matrix have to be transported across two membranes. The TOM and TIM23 complexes facilitate the transport of precursor proteins with N-terminal targeting signals into the matrix. During transport, precursors are recognized by the TIM23 complex in the inner membrane for handover from the TOM complex. However, we have little knowledge on the organization of the TOM-TIM23 transition zone and on how precursor transfer between the translocases occurs. Here, we have designed a precursor protein that is stalled during matrix transport in a TOM-TIM23-spanning manner and enables purification of the translocation intermediate. Combining chemical cross-linking with mass spectrometric analyses and structural modeling allows us to map the molecular environment of the intermembrane space interface of TOM and TIM23 as well as the import motor interactions with amino acid resolution. Our analyses provide a framework for understanding presequence handover and translocation during matrix protein transport.
Topics: Cell Fractionation; Cell Nucleus; Cross-Linking Reagents; Mass Spectrometry; Membrane Transport Proteins; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Membranes; Mitochondrial Precursor Protein Import Complex Proteins; Molecular Docking Simulation; Mutagenesis, Site-Directed; Point Mutation; Protein Binding; Protein Interaction Mapping; Protein Precursors; Recombinant Proteins; Saccharomyces cerevisiae Proteins
PubMed: 34588454
DOI: 10.1038/s41467-021-26016-1