Three new steroidal glycosides, metapregnoside A-c (II-IV), together with one known compound, byzantionoside B (I), were isolated from the fresh whole herb of Metaplexis japonica by using high-speed countercurrent chr...
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Three new steroidal glycosides, metapregnoside A-c (II-IV), together with one known compound, byzantionoside B (I), were isolated from the fresh whole herb of Metaplexis japonica by using high-speed countercurrent chromatography and semi-preparative liquid chromatography. Their structures and relative configurations were elucidated by spectroscopic methods including 1D NMR, 2D NMR and HR-ESI-MS. The potential targets of compound I-IV were identified by virtual screening. And the potential inhibitory effects of these compounds on tyrosine protein kinases were compared by molecular docking. Byzantionoside B (I) was the first isolated compound from Metaplexis genus. The docking score of metapregnoside c (IV) was the highest. And the sugar chain residues at position c-20 in the pregn-4-en-3-one derivatives is the main factor affecting their docking scores on tyrosine protein kinases Fes/Fps.
The death of c. Richard conti, MD, MAcc in February 2022 marked the passing of a global leader in cardiology who played a pivotal role in the history of the American college of cardiology and the college's outreac...
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The death of c. Richard conti, MD, MAcc in February 2022 marked the passing of a global leader in cardiology who played a pivotal role in the history of the American college of cardiology and the college's outreach to the People's Republic of china.
Background The cell division cycle is a process that is exquisitely controlled by a complex interplay between E3 ubiquitin ligases and deubiquitinating enzymes (DUBs). We have previously reported that the DUB USP13 re...
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Background The cell division cycle is a process that is exquisitely controlled by a complex interplay between E3 ubiquitin ligases and deubiquitinating enzymes (DUBs). We have previously reported that the DUB USP13 regulates Aurora B levels along the cell cycle. That observation prompted us to explore any possible connection between USP13 and the APc/c-cDH1, the major E3 controlling Aurora B levels in cells. Methods We performed immunoprecipitation assays followed by western-blotting to assess the interaction between USP13 and cDH1. The cellular effects of USP13 gain or loss of function were analyzed by transfection of FLAG-tagged USP13 plasmid or small interfering RNAs and short hairpin RNAs directed against USP13. The levels of cDH1 and other proteins were quantified in cell extracts by western-blotting. Results We found that USP13 binds to the APc/c adaptor cDH1. In addition, we report for the first time that USP13 controls cDH1 protein levels in cells: overexpression of USP13 increased cDH1 levels, whereas depletion of USP13 decreased cDH1 levels. conclusions We unveil the existing interplay between USP13 and cDH1: USP13 is capable of stabilizing cDH1 levels. We previously reported that USP13 stabilizes Aurora B in cells, a known substrate of the APc/c-cDH1 E3 ubiquitin ligase, before their entry into mitosis. Altogether, our data identify and establish the USP13-cDH1-Aurora B axis as a new regulatory module required for flawless cell cycle progression in mammalian cells, whose misfunction may be involved in the rewiring of cell cycle pathways linked to cancer development.
Epigenetic mechanisms control chromatin accessibility and gene expression to ensure proper cell fate specification. Histone proteins are integral chromatin components, and their modification promotes gene expression r...
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Epigenetic mechanisms control chromatin accessibility and gene expression to ensure proper cell fate specification. Histone proteins are integral chromatin components, and their modification promotes gene expression regulation. Specific proteins recognize modified histones such as the chromodomain protein MRG-1. MRG-1 is the caenorhabditis elegans ortholog of mammalian MRG15, which is involved in DNA repair. MRG-1 binds methylated histone H3 and is important for germline maturation and safeguarding. To elucidate interacting proteins that modulate MRG-1 activity, we performed in-depth protein-protein interaction analysis using immunoprecipitations coupled with mass spectrometry. We detected strong association with the Small ubiquitin-like modifier SUMO, and found that MRG-1 is post-translationally modified by SUMO. SUMOylation affects chromatin-binding dynamics of MRG-1, suggesting an epigenetic regulation pathway, which may be conserved. MULTIDIScIPLINARY ABSTRAcT Epigenetic mechanisms control chromatin accessibility and gene expression to ensure proper cell fate specification. We describe in this study that in the nematode c. elegans, the epigenetic regulator MRG-1 is modified by the small ubiquitin-like modifier SUMO. Posttranslational modification by SUMO affects chromatin-binding dynamics of MRG-1, suggesting a modulation of epigenetic regulation. METHOD SUMMARY co-immunoprecipitation is in combination with single-pot, solid-phase-enhanced, sample preparation (SP3), followed by mass spectrometry (coIP-MS) and label-free quantification (LFQ). TWEETABLE ABSTRAcT SUMOylation of the mammalian epigenetic factor MRG15 ortholog MRG-1 in c. elegans affects chromatin-binding dynamics of MRG-1.
craniosynostosis is a condition of premature fusion of the cranial sutures. Multi-suture craniosynostosis has been found to be associated with a number of syndromes and underlying gene mutations. Tumour necrosis facto...
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craniosynostosis is a condition of premature fusion of the cranial sutures. Multi-suture craniosynostosis has been found to be associated with a number of syndromes and underlying gene mutations. Tumour necrosis factor receptor-associated factors (TRAFs) are a family of adaptor proteins interacting with cell surface receptors or other signalling molecules. TRAF7 is one of the factors involved in multiple biologic processes, including ubiquitination, myogenesis and toll-like receptor signalling. Here, we report a child who presented with multi-suture craniosynostosis and had the uncommon c.1570c>T (***524Trp) variant of TRAF7.
A series of newpara-terphenyls derivatives have been efficiently synthesized by a ligand-free heterogeneous Pd/c-catalyzed two-fold Suzuki-Miyaura coupling reaction. Methyl 5-bromo-2-iodobenzoate was selected to react...
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A series of newpara-terphenyls derivatives have been efficiently synthesized by a ligand-free heterogeneous Pd/c-catalyzed two-fold Suzuki-Miyaura coupling reaction. Methyl 5-bromo-2-iodobenzoate was selected to react with a variety of different aryl boronic acids (2a-i). Nine newp-terphenyl derivatives (3a-i) were prepared and the structures were confirmed by several analytical techniques including infrared, spectroscopy,H-1 and(13)c NMR spectroscopy, mass spectrometry, and in the case of compound3 b,by X-ray diffraction method. The new derivatives were obtained in very good yields (78-91%). This synthetic facile route is envisioned to improve the preparation ofp-terphenyl-based natural products.
In this paper, a comparative study is presented on the application of General-purpose computing on Graphics Processing Units for solving the point reactor kinetics equations through the utilization of the 4th Order Ru...
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In this paper, a comparative study is presented on the application of General-purpose computing on Graphics Processing Units for solving the point reactor kinetics equations through the utilization of the 4th Order RungeKutta (RK4) method using the programming languages c and Python. Sequential and parallel algorithms of the RK4 method were developed in c/c++ and Python, with parallel algorithms specifically designed to operate on Graphics Processing Units (GPUs) utilizing the NVIDIA compute Unified Device Architecture (cUDA) as the programming platform. As an experiment, the execution time for the sequential and parallel algorithms were compared for a reactivity value of rho = 0.003 and a simulation time of t = 100 s. The parallel c and Python algorithms achieved, respectively, speedups of 9.33 and 409.7 when comparing the execution time on the best GPU utilized (RTX 3070Ti) with the best cPU (3600XT), while still maintaining numerical precision.
Background The medicinal effects of cannabis varieties on the market cannot be explained solely by the presence of the major cannabinoids Delta(9)-tetrahydrocannabinol (THc) and cannabidiol (cBD). Evidence for putativ...
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Background The medicinal effects of cannabis varieties on the market cannot be explained solely by the presence of the major cannabinoids Delta(9)-tetrahydrocannabinol (THc) and cannabidiol (cBD). Evidence for putative entourage effects caused by other compounds present in cannabis is hard to obtain due to the subjective nature of patient experience data. caenorhabditis elegans (c. elegans) is an objective test system to identify cannabis compounds involved in claimed health and entourage effects. Methods From a medicinal cannabis breeding program by MariPharm BV, the Netherlands a set of 12 varieties were selected both THc rich varieties as well as cBD rich varieties. A consecutive extraction process was applied resulting in a non-polar (cannabinoid-rich) and polar (cannabinoid-poor) extract of each variety. The test model c. elegans was exposed to these extracts in a broad set of bioassays for appetite control, body oscillation, motility, and nervous system function. Results Exposing c. elegans to extracts with a high concentration of cannabinoids (> 1 mu g/mL) reduces the life span of c. elegans dramatically. Exposing the nematodes to the low-cannabinoid (< 0.005 mu g/mL) polar extracts, however, resulted in significant effects with respect to appetite control, body oscillation, motility, and nervous system-related functions in a dose-dependent and variety-dependent manner. Discussion c. elegans is a small, transparent organism with a complete nervous system, behavior and is due to its genetic robustness and short life cycle highly suitable to unravel entourage effects of cannabis compounds. Although c. elegans lacks an obvious cB1 and cB2 receptor it has orthologs of Serotonin and Vanilloid receptor which are also involved in (endo)cannabinoid signaling. conclusion By using c. elegans, we were able to objectively distinguish different effects of different varieties despite the cannabinoid content. c. elegans seems a useful test system for studying entourage effe
Background Weiss-Kruszka syndrome (WSKA) is a rare disorder caused by mutations in theZNF462gene or deletion of 9p31.2 chromosome region, involvingZNF462. The prevalence of WSKA is unknown as only 24 affected individu...
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Background Weiss-Kruszka syndrome (WSKA) is a rare disorder caused by mutations in theZNF462gene or deletion of 9p31.2 chromosome region, involvingZNF462. The prevalence of WSKA is unknown as only 24 affected individuals have been described. This syndrome should be suspected in individuals presenting mild global developmental delay and common craniofacial abnormalities. case presentation We presented a case of an infant, 3 years and 4-month life who presented pondostatural and psychomotor retardation, generalized hypotonia with hypermobility, bilateral palpebral ptosis, epicanthal folds, and poorly expressive facies as the main clinical features. These characteristics lead to the realization of genetics studies that resulted in the identification of a novel mutation c.3306dup;p.(Gln1103Thrfs*10) inZNF462. conclusions WSKA should be suspected in individuals presenting mild global developmental delay, ptosis, downslanting palpebral fissures, exaggerated cupid's Bow, arched eyebrows, epicanthal folds and short upturned nose with a bulbous tip. Hypertrophy of the ventricular septum and severe OSA were described in our patient and should be considered in future reviews of the disease. This case is added to the reduced number of publications previously reported regarding WSKA and contributes to understanding the geneticcharacteristics, clinical features, and diagnosis of this syndrome.
Purpose Due to the randomness and unpredictability of many disasters, it is essential to be prepared to face difficult conditions after a disaster to reduce human casualties and meet the needs of the people. After the...
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Purpose Due to the randomness and unpredictability of many disasters, it is essential to be prepared to face difficult conditions after a disaster to reduce human casualties and meet the needs of the people. After the disaster, one of the most essential measures is to deliver relief supplies to those affected by the disaster. Therefore, this paper aims to assign demand points to the warehouses as well as routing their related relief vehicles after a disaster considering convergence in the border warehouses. Design/methodology/approach This research proposes a multi-objective, multi-commodity and multi-period queueing-inventory-routing problem in which a queuing system has been applied to reduce the congestion in the borders of the affected zones. To show the validity of the proposed model, a small-size problem has been solved using exact methods. Moreover, to deal with the complexity of the problem, a metaheuristic algorithm has been utilized to solve the large dimensions of the problem. Finally, various sensitivity analyses have been performed to determine the effects of different parameters on the optimal response. Findings According to the results, the proposed model can optimize the objective functions simultaneously, in which decision-makers can determine their priority according to the condition by using the sensitivity analysis results. Originality/value The focus of the research is on delivering relief items to the affected people on time and at the lowest cost, in addition to preventing long queues at the entrances to the affected areas.
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