Dinoflagellates are amongst the most abundant and diverse groups of plankton in surface waters and contribute to food web productivity and c:N:P biogeochemistry. Here we analyse the c:N:P of marine, autotrophic, plank...
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Dinoflagellates are amongst the most abundant and diverse groups of plankton in surface waters and contribute to food web productivity and c:N:P biogeochemistry. Here we analyse the c:N:P of marine, autotrophic, planktonic dinoflagellates compiled from culture data from the scientific literature and test if dinoflagellate c:N:P differs from the Redfield ratio, and whether variability in c:N:P is associated with three traits: cell size, wall structure and toxin production. We find the average c:N:P of dinoflagellates is 90:12:1;higher in c:N, and lower in c:P and N:P than the canonical Redfield ratio. In aggregate the three traits examined here account for between 20-31% while taxonomic order accounts for between 37-38% of the variance in c:N:P. Smaller-sized and thecate taxa are higher in c:N, c:P and N:P than larger-size and athecate taxa. Species known to be able to produce c-rich toxins tend to be higher in c:P and N:P while species known to be able to produce N-rich toxins are lower in c:N, c:P and N:P relative to non-toxic species. These results indicate that any average estimate of dinoflagellate c:N:P will be influenced by the relative number of taxa with these traits.
Purpose In women under the age of 40, primary ovarian insufficiency (POI) is a devastating diagnosis with significant prevalence of 1-4% (Rajkovic and Pangas, Semin Reprod Med. 35(3):231-40, 2017). POI is characterize...
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Purpose In women under the age of 40, primary ovarian insufficiency (POI) is a devastating diagnosis with significant prevalence of 1-4% (Rajkovic and Pangas, Semin Reprod Med. 35(3):231-40, 2017). POI is characterized by amenorrhea with elevated levels of follicle stimulating hormone (FSH) and reduced estrogen levels, mimicking the menopausal state. Genetic determinants account for just over 10% of POI cases, yet determining whether particular single nucleotide polymorphisms (SNPs) are pathogenic is challenging. Methods We performed exome sequencing on a cohort of women with POI. cRISPR mutagenesis was employed to create a mutation in a conserved amino acid in the nematode protein. Functional relevance was assessed by analysis of bivalents and aberrant DNA morphologies in diakinesis nuclei. Results We identified a nonsynonymous c.c1051G;p.R351G variant, in a conserved region of the MSH5 protein. Mutation of this conserved amino acid in the c. elegans homolog, msh-5, revealed defective crossover outcomes in the homozygous and hemizygous states. conclusions These studies further implicate MSH5 as a POI gene and c.c1051G;p.R351G variant as likely playing a functional role in mammalian meiosis. This approach also highlights the ability of model organisms, such as c. elegans, to rapidly and inexpensively identify alleles of interest for further studies in mammalian models.
Polyinosinic-polycytidylic acid (poly I:c) is a synthetic analog of double-stranded RNA (dsRNA) that activates anti-infective innate immunity. The underlying mechanisms are identified as targeting pattern recognition ...
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Polyinosinic-polycytidylic acid (poly I:c) is a synthetic analog of double-stranded RNA (dsRNA) that activates anti-infective innate immunity. The underlying mechanisms are identified as targeting pattern recognition receptors and Th1-inducing. However, whether poly I:c manipulates metabolism to implement this anti-infective function is unknown. Here, Gc-MS based metabolomics was used to characterize metabolic profiles induced by different doses of poly I:c. Analysis on the dose-dependent metabolomes shows that elevation of the TcA cycle and malate with the increasing dose of ploy I:c forms the most characteristic feature of the poly I:c stimulation. Exogenous malate activates the TcA cycle and elevates survival of zebrafish infected with Vibrio alginolyticus, which is related to the elevated expression of il-1b, il-6, il-8, tnf-a, and c3b. These results reveal a previously unknown regulation of poly I:c that boosts the TcA cycle to enhance innate immunity against bacterial infection.
Background Protein-protein interactions form the basis of every organism and thus, investigating their dynamics, intracellular protein localization, trafficking and interactions of distinct proteins such as receptors ...
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Background Protein-protein interactions form the basis of every organism and thus, investigating their dynamics, intracellular protein localization, trafficking and interactions of distinct proteins such as receptors and their ligand-binding are of general interest. Bioluminescence resonance energy transfer (BRET) is a powerful tool to investigate these aspects in vitro. Since in vitro approaches mostly neglect the more complex in vivo situation, we established BRET as an in vivo tool for studying protein interactions in the nematode c. elegans. Results We generated worms expressing NanoBRET sensors and elucidated the interaction of two ligand-G protein-coupled receptor (GPcR) pairs, the neuropeptide receptor NPR-11 and the Adhesion GPcR LAT-1. Furthermore, we adapted the enhanced bystander BRET technology to measure subcellular protein localization. Using this approach, we traced ligand-induced internalization of NPR-11 in vivo. conclusions Our results indicate that in vivo NanoBRET is a tool to investigate specific protein interactions and localization in a physiological setting in real time in the living organism c. elegans.
Due to their elongated and polarized morphology, neurons rely on the microtubule (MT) cytoskeleton for their shape, as well as for efficient intracellular transport that maintains neuronal function, survival, and conn...
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Due to their elongated and polarized morphology, neurons rely on the microtubule (MT) cytoskeleton for their shape, as well as for efficient intracellular transport that maintains neuronal function, survival, and connectivity. Although all MTs are constructed from alpha-and ll-tubulins that are highly conserved throughout eukaryotes, different MT networks within neurons exhibit different dynamics and functions. For example, molecular motors must be able to differentially recognize the axonal and dendritic MTs to deliver appropriate cargos to sensory endings and synaptic regions. The Tubulin code hypothesis proposes that MTs can be specialized in form and function by chemical differences in their composition by inclusion of different alpha-and ll-tubulins into the MT lattice, as well as differences in post-translational enzymatic modifications. The chemical differences encode information that allow MTs to regulate interactions with various microtubule-based molecular motors such as kinesins and dyneins as well as with structural microtubule-associated proteins (MAPs), which can, in turn, modify the function or stability of ***, we review studies involving c. elegans, a model organism with a relatively simple nervous system that is amenable to genetic analysis, that have contributed to our understanding of how the Tubulin code can specialize neuronal MT networks to establish differences in neuronal morphology and function. Such studies have revealed molecules and mechanisms that are conserved in vertebrates and have the potential to inform our understanding of neurological diseases involving defects in the cytoskeleton and intracellular transport.
Introduction Diffuse midline gliomas (DMGs) are infiltrative midline gliomas harboring H3K27M mutations and are generally associated with poor outcomes. H3K27M mutations include mutations in HIST1H3B/c (H3.1), HIST2H3...
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Introduction Diffuse midline gliomas (DMGs) are infiltrative midline gliomas harboring H3K27M mutations and are generally associated with poor outcomes. H3K27M mutations include mutations in HIST1H3B/c (H3.1), HIST2H3B/D (H3.2), or H3F3A (H3.3) genes. It is still unclear whether these mutations each portend a universally poor prognosis, or if there are any factors which modulate outcome. The main objective of this study was to study overall survival (OS) of H3.1 versus H3.3 K27M-mutant DMGs in pediatric and adult patients. Methods PubMed and Web of Science were searched, and we included studies if they have individual patient data of DMGs with available H3K27M genotype. Kaplan-Meier analysis and cox regression models were used to analyze the survival of H3.1 and H3.3 mutations in each subgroup. Results We included 26 studies with 102 and 529 H3.1 and H3.3-mutant DMGs, respectively. The H3.1 mutation was more commonly seen in younger age. In pediatric population, H3.3 mutation conferred a shorter survival (median OS of 10.1 vs 14.2 months;p < 0.001) in comparison to H3.1-positive patients, which was further confirmed in the multivariate cox analysis. conversely, H3.3 was associated with a prolonged survival in adult patients as compared with H3.1 mutation (median OS of 14.4 vs 1.7 months;p = 0.019). conclusion We demonstrated that the prognosis of H3.1 and H3.3 K27M mutation in DMG patients is modulated by patient age. Routine H3K27M mutation genotyping in newly diagnosed DMGs may further stratify patients with these difficult tumors.
Over the past decade, N-heterocycliccarbene (NHc), bipyridine (bpy), and pyridine oxazoline (PyOx) ligands have been increasingly applied in nickel catalysis, where the combination of a low-oxidation-state 3d metal a...
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Over the past decade, N-heterocycliccarbene (NHc), bipyridine (bpy), and pyridine oxazoline (PyOx) ligands have been increasingly applied in nickel catalysis, where the combination of a low-oxidation-state 3d metal and an electron-rich ligand can enable otherwise challenging bond activations. Herein we report the synthesis and characterization of two Ni(0) complexes supported by an alternative, bidentate, c,N ligand, (h)IMesPy ("half-IMes-pyridine" or 1-(2,4,6-trimethylphenyl)-3-(2-pyridinyl)-imidazol-2-ylidene). The unsymmetric ligand combines the strong sigma-donating properties of an NHc with the pi-accepting properties of pyridine to afford homoleptic [Ni((h)IMesPy)(2)] and heteroleptic [Ni(cod)((h)IMesPy)] complexes. characterization through the combination of single-crystal X-ray diffraction analysis and NMR spectroscopy, as well as reactivity studies demonstrating reversible interconversion between the two species, provide a strong basis for future applications to overcome reactivity challenges.
ceRNA effect was an important regulation mode of miRNA mediated bio-activities, however, most of the researches of ceRNA were on ncRNAs synergetic with mRNAs, the exploration of ceRNA effect regulated mRNA interaction...
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ceRNA effect was an important regulation mode of miRNA mediated bio-activities, however, most of the researches of ceRNA were on ncRNAs synergetic with mRNAs, the exploration of ceRNA effect regulated mRNA interaction was still lack of. Besides, c/EBPa was one of the most crucial adipogenic regulators, which has been demonstrated to form a protein complex with FOXO1 to mediate AdipoQ expression. So that, we try to explore whether the ceRNA effect mediated the interaction of c/EBPa and FOXO1, and identified the key miRNAs of their ceRNA effect. In this paper, we found the ceRNA effect of c/EBPa and FOXO1 mediated their protein complex formation, furthermore regulated its transcriptional role for AdipoQ, thereby influencing pre-adipocytes adipogenesis. More importantly, we demonstrated that the miR-144 was the decisive factor that mediated the ceRNA effect of c/EBPa and FOXO1 to influence AdipoQ, thus regulated pre-adipocytes adipogenesis. This research will provide a new supplementary idea of the miRNA role in mediating coding RNA interaction that regulates pre-adipocyte adipogenesis. (c) 2022 Elsevier Inc. All rights reserved.
Background Nucleosome-mediated chromatin compaction has a direct effect on the accessibility of trans-acting activators and repressors to DNA targets and serves as a primary regulatory agent of genetic expression. Und...
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Background Nucleosome-mediated chromatin compaction has a direct effect on the accessibility of trans-acting activators and repressors to DNA targets and serves as a primary regulatory agent of genetic expression. Understanding the nature and dynamics of chromatin is fundamental to elucidating the mechanisms and factors that epigenetically regulate gene expression. Previous work has shown that there are three types of canonical sequences that strongly regulate nucleosome positioning and thus chromatin accessibility: putative nucleosome-positioning elements, putative nucleosome-repelling sequences, and homopolymeric runs of A/T. It is postulated that these elements can be used to remodel chromatin in c. elegans. Here we show the utility of such elements in vivo, and the extreme efficacy of a newly discovered repelling sequence, PRS-322. Results In this work, we show that it is possible to manipulate nucleosome positioning in c. elegans solely using canonical and putative positioning sequences. We have not only tested previously described sequences such as the Widom 601, but also have tested additional nucleosome-positioning sequences: the Trifonov sequence, putative repelling sequence-322 (PRS-322), and various homopolymeric runs of A and T nucleotides. conclusions Using each of these types of putative nucleosome-positioning sequences, we demonstrate their ability to alter the nucleosome profile in c. elegans as evidenced by altered nucleosome occupancy and positioning in vivo. Additionally, we show the effect that PRS-322 has on nucleosome-repelling and chromatin remodeling.
During mitosis, phosphorylation and dephosphorylation of lamins triggers the nuclear envelope disassembly/assembly. However, it hasn't been known whether lamin proteins undergo any modification other than phosphor...
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During mitosis, phosphorylation and dephosphorylation of lamins triggers the nuclear envelope disassembly/assembly. However, it hasn't been known whether lamin proteins undergo any modification other than phosphorylation during the cell cycle. Glycosylation of lamin proteins is one of the less studied post-translational modification. Glycosylation and phosphorylation compete for the same positions and interplay between two modifications generate a post-translational code in the cell. Based on this, we hypothesized that glycosylation of lamin A/c protein may be important in the regulation of the structural organization of the nuclear lamina during interphase and mitosis. We analysed the glycan units of lamin A/c protein in lung carcinoma cells synchronized at G2/M and S phases via capLc-ESI-MS/MS. Besides, the outermost glycan units were determined using lectin blotting and gold-conjugated antibody and lectin staining. TEM studies also allowed us to observe the localization of glycosylated lamin A/c protein. With this study, we determined that lamin A/c protein shows O-glycosylation at G2/M and S phases of the cell cycle. In addition to O-GlcNAcylation and O-GalNAcylation, lamin A/c is found to be contain Gal, Fuc, Man, and Sia sugars at G2/M and S phases for the first time. Having found the glycan units of the lamin A/c protein suggests that glycosylation might have a role in the nuclear organization during the cell cycle.
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