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Blood Advances Jun 2024von Willebrand factor (VWF) undergoes complex posttranslational modification within endothelial cells (ECs) before secretion. This includes significant N- and O-linked...
von Willebrand factor (VWF) undergoes complex posttranslational modification within endothelial cells (ECs) before secretion. This includes significant N- and O-linked glycosylation. Previous studies have demonstrated that changes in N-linked glycan structures significantly influence VWF biosynthesis. In contrast, although abnormalities in VWF O-linked glycans (OLGs) have been associated with enhanced VWF clearance, their effect on VWF biosynthesis remains poorly explored. Herein, we report a novel role for OLG determinants in regulating VWF biosynthesis and trafficking within ECs. We demonstrate that alterations in OLGs (notably reduced terminal sialylation) lead to activation of the A1 domain of VWF within EC. In the presence of altered OLG, VWF multimerization is reduced and Weibel-Palade body (WPB) formation significantly impaired. Consistently, the amount of VWF secreted from WPB after EC activation was significantly reduced in the context of O-glycosylation inhibition. Finally, altered OLG on VWF not only reduced the amount of VWF secreted after EC activation but also affected its hemostatic efficacy. Notably, VWF secreted after WPB exocytosis consisted predominantly of low molecular weight multimers, and the length of tethered VWF string formation on the surface of activated ECs was significantly reduced. In conclusion, our data therefore support the hypothesis that alterations in O-glycosylation pathways directly affect VWF trafficking within human EC. These findings are interesting given that previous studies have reported altered OLG on plasma VWF (notably increased T-antigen expression) in patients with von Willebrand disease.
Topics: von Willebrand Factor; Weibel-Palade Bodies; Humans; Polysaccharides; Glycosylation; Protein Transport; Endothelial Cells; Protein Processing, Post-Translational; Protein Multimerization
PubMed: 38640438
DOI: 10.1182/bloodadvances.2023012499 -
Journal of Agricultural and Food... May 2024Cold-adapted proteases are capable of efficient protein hydrolysis at reduced temperatures, which offer significant potential applications in the area of low temperature...
Cold-adapted proteases are capable of efficient protein hydrolysis at reduced temperatures, which offer significant potential applications in the area of low temperature food processing. In this paper, we attempted to characterize cold-adapted proteases from Antarctic krill. Antarctic krill possesses an extremely active autolytic enzyme system in their bodies, and the production of peptides and free amino acids accompanies the rapid breakdown of muscle proteins following the death. The crucial role of trypsin in this process is recognized. A cold-adapted trypsin named OUC-Pp-20 from Antarctic krill genome was cloned and expressed in . Recombinant trypsin is a monomeric protein of 26.8 ± 1.0 kDa with optimum reaction temperature at 25 °C. In addition, the catalytic specificity of OUC-Pp-20 was assessed by identifying its hydrolysis sites through LC-MS/MS. OUC-Pp-20 appeared to prefer Gln and Asn at the P1 position, which is an amino acid with an amide group in its side chain. Hydrolysis reactions on milk and shrimp meat revealed that it can effectively degrade allergenic components in milk and arginine kinase in shrimp meat. These findings update the current knowledge of cold-adapted trypsin and demonstrate the potential application of OUC-Pp-20 in low temperature food processing.
Topics: Animals; Euphausiacea; Hydrolysis; Cold Temperature; Trypsin; Substrate Specificity; Amino Acid Sequence; Tandem Mass Spectrometry; Enzyme Stability; Antarctic Regions
PubMed: 38628059
DOI: 10.1021/acs.jafc.4c00322 -
BMJ (Clinical Research Ed.) Apr 2024The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) statement was published in 2015 to provide the minimum...
The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) statement was published in 2015 to provide the minimum reporting recommendations for studies developing or evaluating the performance of a prediction model. Methodological advances in the field of prediction have since included the widespread use of artificial intelligence (AI) powered by machine learning methods to develop prediction models. An update to the TRIPOD statement is thus needed. TRIPOD+AI provides harmonised guidance for reporting prediction model studies, irrespective of whether regression modelling or machine learning methods have been used. The new checklist supersedes the TRIPOD 2015 checklist, which should no longer be used. This article describes the development of TRIPOD+AI and presents the expanded 27 item checklist with more detailed explanation of each reporting recommendation, and the TRIPOD+AI for Abstracts checklist. TRIPOD+AI aims to promote the complete, accurate, and transparent reporting of studies that develop a prediction model or evaluate its performance. Complete reporting will facilitate study appraisal, model evaluation, and model implementation.
Topics: Humans; Prognosis; Models, Statistical; Decision Support Techniques; Checklist
PubMed: 38626948
DOI: 10.1136/bmj-2023-078378 -
Spectrochimica Acta. Part A, Molecular... Jul 2024Uyghur medicine is one of the four major ethnic medicines in China and is a component of traditional Chinese medicine. The intrinsic quality of Uyghur medicinal...
Uyghur medicine is one of the four major ethnic medicines in China and is a component of traditional Chinese medicine. The intrinsic quality of Uyghur medicinal materials will directly affect the clinical efficacy of Uyghur medicinal preparations. However, in recent years, problems such as adulteration of Uyghur medicinal materials and foreign bodies with the same name still exist, so it is necessary to strengthen the quality control of Uyghur medicines to guarantee Uyghur medicinal efficacy. Identifying the components of Uyghur medicines can clarify the types of medicinal materials used, is a crucial step to realizing the quality control of Uyghur medicines, and is also an important step in screening the effective components of Uyghur medicines. Currently, the method of identifying the components of Uyghur medicines relies on manual detection, which has the problems of high toxicity of the unfolding agent, poor stability, high cost, low efficiency, etc. Therefore, this paper proposes a method based on Raman spectroscopy and multi-label deep learning model to construct a model Mix2Com for accurate identification of Uyghur medicine components. The experiments use computer-simulated mixtures as the dataset, introduce the Long Short-Term Memory Model (LSTM) and Attention mechanism to encode the Raman spectral data, use multiple parallel networks for decoding, and ultimately realize the macro parallel prediction of medicine components. The results show that the model is trained to achieve 90.76% accuracy, 99.41% precision, 95.42% recall value and 97.37% F1 score. Compared to the traditional XGBoost model, the method proposed in the experiment improves the accuracy by 49% and the recall value by 18%; compared with the DeepRaman model, the accuracy is improved by 9% and the recall value is improved by 14%. The method proposed in this paper provides a new solution for the accurate identification of Uyghur medicinal components. It helps to improve the quality standard of Uyghur medicinal materials, advance the research on screening of effective chemical components of Uyghur medicines and their action mechanisms, and then promote the modernization and development of Uyghur medicine.
Topics: Medicine, East Asian Traditional; Spectrum Analysis, Raman
PubMed: 38626675
DOI: 10.1016/j.saa.2024.124251 -
Journal of Cheminformatics Apr 2024Wiswesser Line Notation (WLN) is a old line notation for encoding chemical compounds for storage and processing by computers. Whilst the notation itself has long since...
PURPOSE
Wiswesser Line Notation (WLN) is a old line notation for encoding chemical compounds for storage and processing by computers. Whilst the notation itself has long since been surpassed by SMILES and InChI, distribution of WLN during its active years was extensive. In the context of modernising chemical data, we present a comprehensive WLN parser developed using the OpenBabel toolkit, capable of translating WLN strings into various formats supported by the library. Furthermore, we have devised a specialised Finite State Machine l, constructed from the rules of WLN, enabling the recognition and extraction of chemical strings out of large bodies of text. Available open-access WLN data with corresponding SMILES or InChI notation is rare, however ChEMBL, ChemSpider and PubChem all contain WLN records which were used for conversion scoring. Our investigation revealed a notable proportion of inaccuracies within the database entries, and we have taken steps to rectify these errors whenever feasible.
SCIENTIFIC CONTRIBUTION
Tools for both the extraction and conversion of WLN from chemical documents have been successfully developed. Both the Deterministic Finite Automaton (DFA) and parser handle the majority of WLN rules officially endorsed in the three major WLN manuals, with the parser showing a clear jump in accuracy and chemical coverage over previous submissions. The GitHub repository can be found here: https://github.com/Mblakey/wiswesser .
PubMed: 38622746
DOI: 10.1186/s13321-024-00831-2 -
ENeuro Apr 2024The medial mammillary bodies (MBs) play an important role in the formation of spatial memories; their dense inputs from hippocampal and brainstem regions makes them well...
The medial mammillary bodies (MBs) play an important role in the formation of spatial memories; their dense inputs from hippocampal and brainstem regions makes them well placed to integrate movement-related and spatial information, which is then extended to the anterior thalamic nuclei and beyond to the cortex. While the anatomical connectivity of the medial MBs has been well studied, much less is known about their physiological properties, particularly in freely moving animals. We therefore carried out a comprehensive characterization of medial MB electrophysiology across arousal states by concurrently recording from the medial MB and the CA1 field of the hippocampus in male rats. In agreement with previous studies, we found medial MB neurons to have firing rates modulated by running speed and angular head velocity, as well as theta-entrained firing. We extended the characterization of MB neuron electrophysiology in three key ways: (1) we identified a subset of neurons (25%) that exhibit dominant bursting activity; (2) we showed that ∼30% of theta-entrained neurons exhibit robust theta cycle skipping, a firing characteristic that implicates them in a network for prospective coding of position; and (3) a considerable proportion of medial MB units showed sharp-wave ripple (SWR) responsive firing (∼37%). The functional heterogeneity of MB electrophysiology reinforces their role as an integrative node for mnemonic processing and identifies potential roles for the MBs in memory consolidation through propagation of SWR-responsive activity to the anterior thalamus and prospective coding in the form of theta cycle skipping.
Topics: Animals; Mammillary Bodies; Male; Neurons; Sleep; Rats; Theta Rhythm; Wakefulness; Rats, Long-Evans; CA1 Region, Hippocampal; Action Potentials; Electrophysiological Phenomena
PubMed: 38621991
DOI: 10.1523/ENEURO.0447-23.2024 -
Chemosphere Jun 2024Plastic products have gained global popularity due to their lightweight, excellent ductility, high durability, and portability. However, out of the 8.3 billion tons of... (Review)
Review
Plastic products have gained global popularity due to their lightweight, excellent ductility, high durability, and portability. However, out of the 8.3 billion tons of plastic waste generated by human activities, 80% of plastic waste is discarded due to improper disposal, and then transformed into microplastic pollution under the combined influence of environmental factors and microorganisms. In this comprehensive study, we present a thorough review of recent advancements in research on the source, distribution, and effect of microplastics. More importantly, we conducted deep research on the catalytic degradation technologies of microplastics in water, including advanced oxidation and photocatalytic technologies, and elaborated on the mechanisms of microplastics degradation in water. Besides, various strategies for mitigating microplastic pollution in aquatic ecosystems are discussed, ranging from policy interventions, the initiative for plastic recycling, the development of efficient catalytic materials, and the integration of multiple technological approaches. This review serves as a valuable resource for addressing the challenge of removing microplastic contaminants from water bodies, offering insights into effective and sustainable solutions.
Topics: Microplastics; Oxidation-Reduction; Water Pollutants, Chemical; Plastics; Catalysis; Recycling; Water
PubMed: 38621489
DOI: 10.1016/j.chemosphere.2024.141939 -
ELife Apr 2024GlcNAcylation is a dynamic post-translational modification that diversifies the proteome. Its dysregulation is associated with neurological disorders that impair...
GlcNAcylation is a dynamic post-translational modification that diversifies the proteome. Its dysregulation is associated with neurological disorders that impair cognitive function, and yet identification of phenotype-relevant candidate substrates in a brain-region specific manner remains unfeasible. By combining an GlcNAc binding activity derived from OGA (OGA) with TurboID proximity labeling in , we developed an GlcNAcylation profiling tool that translates GlcNAc modification into biotin conjugation for tissue-specific candidate substrates enrichment. We mapped the GlcNAc interactome in major brain regions of and found that components of the translational machinery, particularly ribosomal subunits, were abundantly GlcNAcylated in the mushroom body of brain. Hypo-GlcNAcylation induced by ectopic expression of active OGA in the mushroom body decreased local translational activity, leading to olfactory learning deficits that could be rescued by dMyc overexpression-induced increase of protein synthesis. Our study provides a useful tool for future dissection of tissue-specific functions of GlcNAcylation in , and suggests a possibility that GlcNAcylation impacts cognitive function via regulating regional translational activity in the brain.
Topics: Animals; Drosophila; Mushroom Bodies; Brain; Cognition; Protein Processing, Post-Translational
PubMed: 38619103
DOI: 10.7554/eLife.91269 -
Materials (Basel, Switzerland) Mar 2024The restoration of ancient ceramics has attracted widespread attention as it can reveal the overall appearance of ancient ceramics as well as the original information...
The restoration of ancient ceramics has attracted widespread attention as it can reveal the overall appearance of ancient ceramics as well as the original information and artistic charm of cultural relics. However, traditional manual restoration is constrained due to its time-consuming nature and susceptibility to damaging ancient ceramics. Herein, a three-dimensional (3D) printing technique was employed to accurately restore Chinese Yuan Dynasty Longquan celadon using hollow AlO microsphere-modified 3D printing paste. The results show that the hollow AlO microsphere content plays a vital role in the printability, physical properties, and firing performance of the modified 3D printing paste. The printed green bodies show no noticeable spacing or voids under moderate rheological conditions. The as-prepared ceramic body modified with 6 wt.% hollow AlO microspheres and fired at 1280 °C exhibits optimal bending strength of 56.66 MPa and a relatively low density of 2.16 g∙cm, as well as a relatively uniform longitudinal elastic modulus and hardness along the interlayer. This 3D printing technique based on hollow AlO microsphere-modified paste presents a promising pathway for achieving non-contact and damage-free restoration of cultural relics.
PubMed: 38612119
DOI: 10.3390/ma17071603 -
Frontiers in Physiology 2024The mosquito is an important vector of diseases including dengue, Zika, chikungunya, and yellow fever. Olfaction is a critical modality for mosquitoes enabling them to...
The mosquito is an important vector of diseases including dengue, Zika, chikungunya, and yellow fever. Olfaction is a critical modality for mosquitoes enabling them to locate hosts, sources of nectar, and sites for oviposition. GABA is an essential neurotransmitter in olfactory processing in the insect brain, including the primary olfactory center, the antennal lobe. Previous work with has suggested that antennal lobe inhibition via GABA may be involved in the processing of odors. However, little is known about GABA receptor expression in the mosquito brain, or how they may be involved in odor attraction. In this context, generating mutants that target the mosquito's olfactory responses, and particularly the GABAergic system, is essential to achieve a better understanding of these diverse processes and olfactory coding in these disease vectors. Here we demonstrate the potential of a transgenic line using the QF2 transcription factor, GABA-B1, as a new neurogenetic tool to investigate the neural basis of olfaction in Our results show that the gene insertion has a moderate impact on mosquito fitness. Moreover, the line presented here was crossed with a QUAS reporter line expressing the green fluorescent protein and used to determine the location of the metabotropic GABA-B1 receptor expression. We find high receptor expression in the antennal lobes, especially the cell bodies surrounding the antennal lobes. In the mushroom bodies, receptor expression was high in the Kenyon cells, but had low expression in the mushroom body lobes. Behavioral experiments testing the fruit odor attractants showed that the mutants lost their behavioral attraction. Together, these results show that the GABA-B1 line provides a new tool to characterize GABAergic systems in the mosquito nervous system.
PubMed: 38606012
DOI: 10.3389/fphys.2024.1381164