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Trends in Environmental Analytical... Jun 2024High resolution mass spectrometry (HRMS) has become an important tool in environmental and food safety analysis. This review highlights how HRMS has been used to analyze...
High resolution mass spectrometry (HRMS) has become an important tool in environmental and food safety analysis. This review highlights how HRMS has been used to analyze chemical contaminants in fish. Measuring and documenting chemical contaminants in fish serves not only as an indicator of environmental conditions but can also monitor the health of these animals and help protect an important source of human food. The incidence and significance of contaminants including veterinary drugs, human drugs and personal care products, pesticides, persistent organic pollutants, per- and poly fluorinated substances, and marine toxins will be reviewed. The advantage of HRMS over traditional MS is its ability to expand the number of compounds that can be detected and identified. This is true whether HRMS is used for targeted analytes, or more broadly for suspect screening and nontargeted analyses. The classes of compounds, types of fish or seafood, options for data acquisition and analysis, and reports of unexpected findings from recent HMRS methods for chemical contaminants in fish are summarized.
PubMed: 38957876
DOI: 10.1016/j.teac.2024.e00227 -
Green Chemistry : An International... Jul 2024Humins, (side-)products of the acid-catalysed dehydration of carbohydrates, will be produced in substantial quantities with the development of industrial biorefining...
Humins, (side-)products of the acid-catalysed dehydration of carbohydrates, will be produced in substantial quantities with the development of industrial biorefining processes. Most structural knowledge about such humins is based on synthetic model humins prepared at lab-scale from typical carbohydrate(-derived) compounds. Here, we report the first extensive characterisation study of an industrial humin. The soluble humin was generated from pilot plant-scale methanolic cyclodehydration of D-fructose to 5-methoxymethyl-2-furfural (MMF), as part of the Avantium YXY® process to produce FDCA. Purification of the industrial humin followed by fractionation allowed isolation of a water-insoluble, high molecular weight fraction (WIPIH) and a water-soluble, low-to-middle molecular weight soluble fraction (WES). Characterisation by elemental analysis, thermogravimetry, IR and NMR spectroscopy and size exclusion chromatography provided a detailed picture of the humin structure in both fractions. Aided by a comprehensive NMR spectral library of furanic model compounds, we identified the main furanic building blocks and inter-unit linkages and propose a structure for this industrial humin sample. The WIPIH and WES fractions were found to be composed of furanic rings interconnected by short aliphatic chains containing a wide range of functionalities including alcohols, ethers, carboxylic acids, esters, aldehydes and ketones. The low level of crosslinking and high functional group content of the industrial humin differ from the more extensively studied, (highly over-)condensed synthetic model humins, towards which they can be considered intermediates. The structural and compositional insights into the nature of an actual industrial humin open up a broad spectrum of valorisation opportunities.
PubMed: 38957875
DOI: 10.1039/d4gc00429a -
Frontiers in Genetics 2024To analyze the prenatal diagnosis, parental verification, and pregnancy outcomes of three fetuses with 17ql2 microdeletion syndrome.
PURPOSE
To analyze the prenatal diagnosis, parental verification, and pregnancy outcomes of three fetuses with 17ql2 microdeletion syndrome.
METHODS
We retrospectively reviewed 46 singleton pregnancies with anomalies in the urinary system who underwent amniocentesis from Feb 2022 to October 2023 in the Prenatal Diagnosis Center of Lianyungang Maternal and Child Health Hospital. These fetuses were subjected to chromosomal microarray analysis (CMA) and/or trio whole-exome sequencing (Trio-WES). We specifically evaluated these cases' prenatal renal ultrasound findings and clinical characteristics of the affected parents.
RESULTS
Three fetuses were diagnosed as 17q12 microdeletions, and the detection rate was 6.5% in fetuses with anomalies in the urinary system (3/46). The heterogeneous deletions range from 1.494 to 1.66 Mb encompassing the complete hepatocyte nuclear factor 1 homeobox B () gene. Fetuses with 17q12 deletion exhibited varied renal phenotypes. Moreover, the clinical phenotypes of the affected parents differed greatly in the two cases (case 2 and case 3) in which the deletion was inherited. For case 3, the mother manifested classic symptoms of 17q12 deletion syndrome as well as unreported characteristics, such as very high myopia.
CONCLUSION
Our findings demonstrate the necessity and significance of offering prenatal genetic testing when various renal anomalies are detected. In addition, our study broadens the phenotypic spectrum of 17q12 deletions. Most importantly, our findings may allow timely supportive genetic counseling and guidance for pregnancy in affected families, e.g., with the help of preimplantation genetic testing (PGT).
PubMed: 38957807
DOI: 10.3389/fgene.2024.1401315 -
IScience Jun 2024The initiation of transcription in Escherichia coli () is facilitated by promoter specificity factors, also known as σ factors, which may bind a promoter only as part...
The initiation of transcription in Escherichia coli () is facilitated by promoter specificity factors, also known as σ factors, which may bind a promoter only as part of a complex with RNA polymerase (RNAP). By performing cross-linking mass spectrometry (CL-MS) of apo-σ, we reveal structural features suggesting a compact conformation compared to the known RNAP-bound extended conformation. Then, we validate the existence of the compact conformation using CL-MS by identifying cross-links similar to those found , which deviate from the extended conformation only during the stationary phase of bacterial growth. Conclusively, we provide information in support of a compact conformation of apo-σ that exists in live cells, which might represent a transcriptionally inactive form that can be activated upon binding to RNAP.
PubMed: 38957792
DOI: 10.1016/j.isci.2024.110140 -
Journal of Craniovertebral Junction &... 2024Missed diagnosis of evolving or coexisting idiopathic (IIH) and spontaneous intracranial hypotension (SIH) is often the reason for persistent or worsening symptoms after...
Is foramen magnum decompression for acquired Chiari I malformation like putting a finger in the dyke? - A simplistic overview of artificial intelligence in assessing critical upstream and downstream etiologies.
BACKGROUND
Missed diagnosis of evolving or coexisting idiopathic (IIH) and spontaneous intracranial hypotension (SIH) is often the reason for persistent or worsening symptoms after foramen magnum decompression for Chiari malformation (CM) I. We explore the role of artificial intelligence (AI)/convolutional neural networks (CNN) in Chiari I malformation in a combinatorial role for the first time in literature, exploring both upstream and downstream magnetic resonance findings as initial screening profilers in CM-1. We have also put together a review of all existing subtypes of CM and discuss the role of upright (gravity-aided) magnetic resonance imaging (MRI) in evaluating equivocal tonsillar descent on a lying-down MRI. We have formulated a workflow algorithm MaChiP 1.0 (Manjila Chiari Protocol 1.0) using upstream and downstream profilers, that cause de novo or worsening Chiari I malformation, which we plan to implement using AI.
MATERIALS AND METHODS
The PRISMA guidelines were used for "CM and machine learning and CNN" on PubMed database articles, and four articles specific to the topic were encountered. The radiologic criteria for IIH and SIH were applied from neurosurgical literature, and they were applied between primary and secondary (acquired) Chiari I malformations. An upstream etiology such as IIH or SIH and an isolated downstream etiology in the spine were characterized using the existing body of literature. We propose the utility of using four selected criteria for IIH and SIH each, over MRI T2 images of the brain and spine, predominantly sagittal sequences in upstream etiology in the brain and multiplanar MRI in spinal lesions.
RESULTS
Using MaChiP 1.0 (patent/ copyright pending) concepts, we have proposed the upstream and downstream profilers implicated in progressive Chiari I malformation. The upstream profilers included findings of brain sagging, slope of the third ventricular floor, pontomesencephalic angle, mamillopontine distance, lateral ventricular angle, internal cerebral vein-vein of Galen angle, and displacement of iter, clivus length, tonsillar descent, etc., suggestive of SIH. The IIH features noted in upstream pathologies were posterior flattening of globe of the eye, partial empty sella, optic nerve sheath distortion, and optic nerve tortuosity in MRI. The downstream etiologies involved spinal cerebrospinal fluid (CSF) leak from dural tear, meningeal diverticula, CSF-venous fistulae, etc.
CONCLUSION
AI would help offer predictive analysis along the spectrum of upstream and downstream etiologies, ensuring safety and efficacy in treating secondary (acquired) Chiari I malformation, especially with coexisting IIH and SIH. The MaChiP 1.0 algorithm can help document worsening of a previously diagnosed CM-1 and find the exact etiology of a secondary CM-I. However, the role of posterior fossa morphometry and cine-flow MRI data for intracranial CSF flow dynamics, along with advanced spinal CSF studies using dynamic myelo-CT scanning in the formation of secondary CM-I is still being evaluated.
PubMed: 38957754
DOI: 10.4103/jcvjs.jcvjs_160_23 -
Environmental Science. Advances Jul 2024In this study, we evaluated the suitability of elutriation, a method successfully employed in the extraction of microplastics from marine sediments, for the extraction...
In this study, we evaluated the suitability of elutriation, a method successfully employed in the extraction of microplastics from marine sediments, for the extraction of microplastics from freshwater and terrestrial soils. Five soils were sampled throughout Oklahoma, USA in order to capture a range of sand, silt, clay, and organic matter composition. Each soil was subjected to microplastic extraction with and without elutriation, followed by digestion in 7.5% NaOCl, and then flotation in 6 M ZnCl. The mass of each soil was measured after elutriation to determine sample mass reduction, and multiple methods including fluorescence imaging and automated particle counting through ImageJ, Attenuated Total Reflectence-Fourier Transfor Infrared Spectroscopy (ATR-FTIR), and Pyrolysis-coupled Gas Chromatography/Mass Spectrometry (py-GC/MS) were used to determine microplastic quantity, mass, and characteristics. -test was used to check for statistically-significant differences between methods in terms of mass or particle quantity. For all tested soils, elutriation resulted in greater sample mass reduction than non-elutriated samples, and was between 59.0-97.3% for the tested soils. Furthermore, no statistically significant ( < 0.05) differences were observed in particle quantification or polymer mass between methods, and no differences were observed for polymer or size distribution. Additionally, 33% more polymers were positively identified ( = 70%) by ATR-FTIR analysis in elutriated samples compared to non-elutriated soils. The mass reduction provided by elutriation allows for the processing of larger sample volumes, leading to greater accuracy and sensitivity in detecting microplastics. As such, we recommend elutriation be performed as a pretreatment step to extract microplastics from soils.
PubMed: 38957706
DOI: 10.1039/d4va00087k -
Cureus Jul 2024This study describes an unusual case of multiple myeloma that progressed to anaplastic multiple myeloma in the pleural fluid. The Wright-stained cytospin of the pleural...
This study describes an unusual case of multiple myeloma that progressed to anaplastic multiple myeloma in the pleural fluid. The Wright-stained cytospin of the pleural fluid showed a predominant population of mononuclear plasma cells with pleomorphic nuclei, characterized by both small and large nuclei, which is typical of anaplastic multiple myeloma. However, there were also more binuclear plasma cells with pleomorphic nuclei. Morphometric analysis showed that the mean nuclear length was 1.9-fold and 2.3-fold higher in the large nuclei compared to the small nuclei for the mononuclear plasma cells and binuclear plasma cells, respectively (p<0.001). The patient received B cell maturation antigen chimeric antigen receptor T cell (CAR-T) therapy for relapsed disease, with a significant reduction of the serum monoclonal paraprotein level at day 51 post-therapy. Pathologists should be aware that pleomorphic binuclear plasma cells can be part of the morphologic spectrum in anaplastic multiple myeloma.
PubMed: 38957510
DOI: 10.7759/cureus.63597 -
PNAS Nexus Jul 2024The Fanconi anemia (FA) repair pathway governs repair of highly genotoxic DNA interstrand crosslinks (ICLs) and relies on translesion synthesis (TLS). TLS is facilitated...
The Fanconi anemia (FA) repair pathway governs repair of highly genotoxic DNA interstrand crosslinks (ICLs) and relies on translesion synthesis (TLS). TLS is facilitated by REV1 or site-specific monoubiquitination of proliferating cell nuclear antigen (PCNA) (PCNA-Ub) at lysine 164 (K164). A but not mutation renders mammals hypersensitive to ICLs. Besides the FA pathway, alternative pathways have been associated with ICL repair (1, 2), though the decision making between those remains elusive. To study the dependence and relevance of PCNA-Ub in FA repair, we intercrossed mice. A combined mutation ( ) was found embryonically lethal. RNA-seq of primary double-mutant (DM) mouse embryonic fibroblasts (MEFs) revealed elevated levels of replication stress-induced checkpoints. To exclude stress-induced confounders, we utilized a knock-down to obtain a model to study ICL repair in depth. Regarding ICL-induced cell toxicity, cell cycle arrest, and replication fork progression, single-mutant and DM MEFs were found equally sensitive, establishing PCNA-Ub to be critical for FA-ICL repair. Immunoprecipitation and spectrometry-based analysis revealed an unknown role of PCNA-Ub in excluding mismatch recognition complex MSH2/MSH6 from being recruited to ICLs. In conclusion, our results uncovered a dual function of PCNA-Ub in ICL repair, i.e. exclude MSH2/MSH6 recruitment to channel the ICL toward canonical FA repair, in addition to its established role in coordinating TLS opposite the unhooked ICL.
PubMed: 38957451
DOI: 10.1093/pnasnexus/pgae242 -
Frontiers in Oncology 2024Lung cancer persistently leads as the primary cause of morbidity and mortality among malignancies. A notable increase in the prevalence of lung adenocarcinoma has become... (Review)
Review
Lung cancer persistently leads as the primary cause of morbidity and mortality among malignancies. A notable increase in the prevalence of lung adenocarcinoma has become evident in recent years. Although targeted therapies have shown in treating certain subsets of non-small cell lung cancers (NSCLC), a significant proportion of patients still face suboptimal therapeutic outcomes. Neuregulin-1 (NRG1), a critical member of the gene family, initially drew interest due to its distribution within the nascent ventricular endocardium, showcasing an exclusive presence in the endocardium and myocardial microvessels. Recent research has highlighted NRG1's pivotal role in the genesis and progression across a spectrum of tumors, influencing molecular perturbations across various tumor-associated signaling pathways. This review provides a concise overview of NRG1, including its expression patterns, configuration, and fusion partners. Additionally, we explore the unique features and potential therapeutic strategies for NRG1 fusion-positive occurrences within the context of NSCLC.
PubMed: 38957319
DOI: 10.3389/fonc.2024.1405380 -
Biological Psychiatry Global Open... Jul 2024Sex-differential biology may contribute to the consistently male-biased prevalence of autism spectrum disorder (ASD). Gene expression differences between males and...
BACKGROUND
Sex-differential biology may contribute to the consistently male-biased prevalence of autism spectrum disorder (ASD). Gene expression differences between males and females in the brain can indicate possible molecular and cellular mechanisms involved, although transcriptomic sex differences during human prenatal cortical development have been incompletely characterized, primarily due to small sample sizes.
METHODS
We performed a meta-analysis of sex-differential expression and co-expression network analysis in 2 independent bulk RNA sequencing datasets generated from cortex of 273 prenatal donors without known neuropsychiatric disorders. To assess the intersection between neurotypical sex differences and neuropsychiatric disorder biology, we tested for enrichment of ASD-associated risk genes and expression changes, neuropsychiatric disorder risk genes, and cell type markers within identified sex-differentially expressed genes (sex-DEGs) and sex-differential co-expression modules.
RESULTS
We identified 101 significant sex-DEGs, including Y-chromosome genes, genes impacted by X-chromosome inactivation, and autosomal genes. Known ASD risk genes, implicated by either common or rare variants, did not preferentially overlap with sex-DEGs. We identified 1 male-specific co-expression module enriched for immune signaling that is unique to 1 input dataset.
CONCLUSIONS
Sex-differential gene expression is limited in prenatal human cortex tissue, although meta-analysis of large datasets allows for the identification of sex-DEGs, including autosomal genes that encode proteins involved in neural development. Lack of sex-DEG overlap with ASD risk genes in the prenatal cortex suggests that sex-differential modulation of ASD symptoms may occur in other brain regions, at other developmental stages, or in specific cell types, or may involve mechanisms that act downstream from mutation-carrying genes.
PubMed: 38957312
DOI: 10.1016/j.bpsgos.2024.100321