18 research outputs found

    The Role of SPARC Protein Expression in the Progress of Gastric Cancer

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    We aimed to investigate the expression of SPARC (secreted protein, acidic and rich in cysteine) in gastric cancer and its relationship with tumor angiogenesis and cancer cells proliferation. Protein expression of SPARC, VEGF, CD34 and Ki-67 in 80 cases of gastric cancer and 30 cases of normal gastric tissue was evaluated by immunohistochemistry. CD34 staining was used as an indicator of microvessel density (MVD). Ki-67 labeling Index (LI) indicated cancer cells proliferation. Statistical analysis was used to investigate its relationship with clinical characteristics, tumor angiogenesis and cancer cells proliferation. SPARC expression was mainly in the stromal cells surrounding the gastric cancer cells, and was statistically significant differences between gastric cancer and normal gastric tissue (P < 0.05). Both the expression of SPARC and VEGF were related to differentiation degree, clinical stage, Lauren classification and lymph node metastasis (P < 0.05). Expression of SPARC was significantly negatively correlated with the expression of VEGF and MVD in gastric cancer tissues. Expression of SPARC was also negatively correlated with Ki-67-LI. Our findings suggest that both the expression of SPARC and VEGF are closed to tumor angiogenesis in gastric cancer, SPARC inhibited tumor angiogenesis but VEGF promoted tumor angiogenesis. SPARC also inhibited cells proliferation of gastric cancer

    Phosphorylation of Neuralized at Serine 94 and 96 is Required for Notch Signaling during Drosophila Development

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    The Notch (N) signaling pathway defines one of the most fundamental signaling pathways that govern metazoan development. Neuralized (Neur) and Mindbomb (Mib), E3 ubiquitin ligases, are essential activators of the N pathway. They are responsible for ubiquitinating and mediating the endocytosis of N ligands, Delta (Dl) and Serrate (Ser). Whereas the functions of Neur are well characterized, how Neur itself is regulated is less well understood. I have identified several phosphorylated residues in Neur including residues S94 and S96. I have determined that phosphorylation of these residues is required for Neur function in embryonic neurogenesis and shown that overexpression of phosphorylation defective mutants leads to defects in sensory organ development inM.Sc

    Disentangling a Bad Reputation: Changing Perceptions of Amyloids

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    Historically, amyloids were perceived as toxic/irreversible protein aggregates associated with neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. Recent papers are challenging this perception by uncovering widespread cellular roles for physiological amyloidogenesis. These findings suggest that the amyloid-fold should be considered, alongside the native-fold and unfolded configurations, as a physiological and reversible protein organization. Cells exploit the amyloid fibrillation propensity of proteins in physiology. Systemic physiological amyloidogenesis programs induce a state of dormancy. Amyloid-like assemblies exhibit properties of solid-state protein organization. Insights from physiological amyloidogenesis open potential novel avenues of investigation for amyloid pathogenesis

    Primary amino acids affect the distribution of methylmercury rather than inorganic mercury among tissues of two farmed-raised fish species

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    The distributions of primary amino acids, MeHg and IHg in body tissues of two commonly farm-raised fish species (common carp: Cyprinus carpio; grass carp: Ctenopharyngodon idellus) in Guizhou Province, SW China, were investigated to understand the effects of primary amino acids on MeHg and Wig metabolism in farm-raised fish. The primary amino acids were classified into four groups: (1) essential and polar amino acids; (2) essential and non-polar amino acids; (3) non-essential and polar amino acids; and (4) non-essential and non-polar amino acids. For both fish species, groups (1, 2 and 3) were enriched in muscle and kidney, whereas group (4) was enriched in scale. The two fish species showed low MeHg concentrations (grass carp: 0.5-3.9 ng/g; common carp:1.0-7.4 ng/g) and low MeHg proportions (grass carp: 2-45%; common carp: 6-37%) in their tissues, which are mainly due to the simple food web structures and the fast growth of the farm-raised fish. Positive correlations (r = 0.342 to 0.472; p < 0.01; n = 78) were observed between MeHg and several primary amino acids (cysteine, threonine, phenylalanine, leucine, valine, glutamate serine and tyrosine) in fish tissues, which may be driven by the formation of MeHg-Cys complexes within fish body. However, no significant correlations were observed between IHg and any primary amino acids, indicating the metabolic processes of IHg and MeHg are different. This study advances our understanding that cysteine and its related/derived amino acids may be an important driving force for MeHg distribution and translocation in fish. (C) 2019 Elsevier Ltd. All rights reserved

    Stress-Induced Low Complexity RNA Activates Physiological Amyloidogenesis

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    Summary: Amyloid bodies (A-bodies) are inducible membrane-less nuclear compartments composed of heterogeneous proteins that adopt an amyloid-like state. A-bodies are seeded by noncoding RNA derived from stimuli-specific loci of the rDNA intergenic spacer (rIGSRNA). This raises the question of how rIGSRNA recruits a large population of diverse proteins to confer A-body identity. Here, we show that long low-complexity dinucleotide repeats operate as the architectural determinants of rIGSRNA. On stimulus, clusters of rIGSRNA with simple cytosine/uracil (CU) or adenosine/guanine (AG) repeats spanning hundreds of nucleotides accumulate in the nucleolar area. The low-complexity sequences facilitate charge-based interactions with short cationic peptides to produce multiple nucleolar liquid-like foci. Local concentration of proteins with fibrillation propensity in these nucleolar foci induces the formation of an amyloidogenic liquid phase that seeds A-bodies. These results demonstrate the physiological importance of low-complexity RNA and repetitive regions of the genome often dismissed as “junk” DNA. : Wang et al. report the identification of stress-induced low-complexity ribosomal intergenic RNA that drive the formation of an amyloidogenic liquid-like phase. Concentration of proteins with fibrillation propensity by low-complexity RNA initiates an amyloidogenic program that confers A-body identity. Keywords: nucleolus, rDNA intergenic spacer, junk DNA, amyloidogenesis, phase separation, beta-amyloid, liquid-to-solid phase transition, complex coacervation, lncRNA, architectural RN

    Local translation in nuclear condensate amyloid bodies

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    Biomolecular condensates concentrate molecules to facilitate basic biochemical processes, including transcription and DNA replication. While liquid-like condensates have been ascribed various functions, solid-like condensates are generally thought of as amorphous sites of protein storage. Here, we show that solid-like amyloid bodies coordinate local nuclear protein synthesis (LNPS) during stress. On stimulus, translationally active ribosomes accumulate along fiber-like assemblies that characterize amyloid bodies. Mass spectrometry analysis identified regulatory ribosomal proteins and translation factors that relocalize from the cytoplasm to amyloid bodies to sustain LNPS. These amyloidogenic compartments are enriched in newly transcribed messenger RNA by Heat Shock Factor 1 (HSF1). Depletion of stress-induced ribosomal intergenic spacer noncoding RNA (rIGSRNA) that constructs amyloid bodies prevents recruitment of the nuclear protein synthesis machinery, abolishes LNPS, and impairs the nuclear HSF1 response. We propose that amyloid bodies support local nuclear translation during stress and that solid-like condensates can facilitate complex biochemical reactions as their liquid counterparts can
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