43 research outputs found
(Eschscholtz, 1823) (Decapoda: Astacidea: Astacidae)
No full textArslan, Kaan, Saglam, Berk, Beyatli, Nazli Coskun, Taskiran, Ekim Z., Bastug, Turgut, Purali, Nuhan (2023): Cloning and functional characterization of a TMC-like channel gene and protein in the crayfish Astacus leptodactylus (Eschscholtz, 1823) (Decapoda: Astacidea: Astacidae). Journal of Crustacean Biology 43 (2): 1-8, DOI: 10.1093/jcbiol/ruad032, URL: http://dx.doi.org/10.1093/jcbiol/ruad03
Effector Th1 cells under <scp>PD</scp> ‐1 and <scp>CTLA</scp> ‐4 checkpoint blockade abrogate the upregulation of multiple inhibitory receptors and by‐pass exhaustion
No full textImmune checkpoint inhibitor (ICI) immunotherapy relies on the restoration of T-cell functions. The ICI receptors are not only found on exhausted T cells but also upregulated upon activation and reach high levels on effector T cells. In an ex vivo model, this study explored the consequences of PD-1 and cytotoxic T-lymphocyte antigen (CTLA-4) blockade applied during specific time frames of T-cell stimulation that coincide with distinct functional phases in type 1 helper T (Th1) cells. When applied at an early stimulation stage, the checkpoint blockade interfered with the upregulation of multiple inhibitory receptors such as PD-1, LAG3, TIM-3 and CTLA-4. Moreover, extension of the blockade period restricted the hyporesponsiveness in T cells. Alternatively, a short-term ICI treatment was advantageous when applied at late time frames of Th1 cell stimulation. Here, a transition phase from effector to exhausted state, which coincided with the late time frames of Th1 stimulation, was clearly determined together with the transcriptomics data demonstrating the initiation of significant alterations in metabolic pathways, genetic information processes, effector and exhaustion specific pathways. Applied in this transition phase, PD-1 and/or CTLA-4 blockade downregulated the inhibitory receptors which were already present on the effector Th1 cells, potentially through endocytic pathways. Therefore, the efficacy of ICI therapy was modulated by the functional status of T cells and can be improved by modifying the timing and duration of PD-1 and CTLA-4 blockade. In conclusion, the ICI therapy not only supports the reactivation of T cells but can also constrain de novo exhaustion
Expression of ASC in post-mortem brain samples of Alzheimer's disease patients: A possible role for ASC in A beta amyloid formation
No full textAim: Amyloid is an extracellular insoluble protein aggregate which accumulates in several tissues in various clinical conditions. The co-localization of ASC, a key molecule in both apoptotic and inflammatory processes, with AA type amyloid fibrils has previously been demonstrated by our group. The aim of this study was to determine whether the distribution of ASC is altered around A beta deposits and senile plaques in post-mortem brain samples of Alzheimer's disease patients
Expression of ASC in post-mortem brain samples of alzheimer's disease patients: A possible role for ASC in aβ amyloid formation alzheimer hastalarının post-mortem beyin dokusu örneklerinde ASC ifadesi: Aβ amyloid oluşumunda ASC'nin rolü
No full textAim: Amyloid is an extracellular insoluble protein aggregate which accumulates in several tissues in various clinical conditions. The co-localization of ASC, a key molecule in both apoptotic and inflammatory processes, with AA type amyloid fibrils has previously been demonstrated by our group. The aim of this study was to determine whether the distribution of ASC is altered around Aβ deposits and senile plaques in post-mortem brain samples of Alzheimer's disease patients. Material and Methods: Immunohistochemical and immunofluorescence staining of paraffin-embedded tissues from post-mortem brain samples of 12 Alzheimer's disease patients were performed using anti-ASC and anti-Aβ antibodies. Then we investigated possible ASC- Aβ co-localization in an in-vitro system using COS-7 cells. Results: Immunohistochemical staining of paraffin-embedded tissues revealed co-localization of ASC protein with Aβ peptide in senile plaques. We further demonstrated the interaction between ASC and Aβ in ASC-YFP and amyloid precursor protein co-transfected COS-7 cells which also showed that specks are located near the intracellular Aβ deposits. Conclusion: We hypothesize that expression of ASC may be important in the pathogenesis of Aβ amyloid formation and in senile plaque development in predisposed tissues. Further functional studies are required to explore the link between ASC and Aβ amyloid formation. Key Words: ASC, Aβ, APP, Alzheimer's disease, inflammation, COS-7 cell line. © TurkJBiochem.com
Expression of ASC in post-mortem brain samples of Alzheimer's disease patients: A possible role for ASC in A beta amyloid formation
No full textAim: Amyloid is an extracellular insoluble protein aggregate which accumulates in several tissues in various clinical conditions. The co-localization of ASC, a key molecule in both apoptotic and inflammatory processes, with AA type amyloid fibrils has previously been demonstrated by our group. The aim of this study was to determine whether the distribution of ASC is altered around A beta deposits and senile plaques in post-mortem brain samples of Alzheimer's disease patients
Critical equimatchable graphs
No full textA graph G is equimatchable if every maximal matching of G has the same cardinality. In this paper, we investigate equimatchable graphs such that the removal of any edge creates a graph that is not equimatchable, called edge-critical equimatchable graphs (ECE-graphs). We show that apart from two simple cases, namely bipartite ECE-graphs and even cliques, all ECE-graphs are 2-connected factor-critical. Accordingly, we give a characterization of factor-critical ECE-graphs with connectivity 2. Our result provides a partial answer to an open question posed by Levit and Mandrescu [Eur. J. Comb. 20 (2019), 261–272] on the characterization of well-covered graphs with no shedding vertex. We also introduce equimatchable graphs such that the removal of any vertex creates a graph that is not equimatchable, called vertex-critical equimatchable graphs (VCEgraphs). To conclude, we clarify the relationship between various subclasses of equimatchable graphs (including ECE-graphs and VCE-graphs) and discuss the properties of factor-critical ECE-graphs with connectivity at least 3. © The author(s).Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, TÜBİTAK, (121F018
Development, Characterization And Research Of Efficacy On In Vitro Cell Culture Of Glucosamine Carrying Hyaluronic Acid Nanoparticles
No full textIntra-articular hyaluronic acid (HA) and oral glucosamine (GA) are frequently used to decrease pain and increase function in osteoarthritis patients. Injectable chondroitin sulfate and HA improve effectiveness however a formulation that combines GA and HA is currently not available. Aims of this study were to synthesize and characterize N-acetyl-d-GA immobilized HA based nanoparticles [GA-PEG@nano(HA)] to increase extracellular matrix production and to decrease OA markers of healthy and OA chondrocytes. Mean size of synthesized GA-PEG@nano(HA) was 175 nm and 20% of GA released from these composites during 21 days. Released GA reduced the proliferation of chondrosarcoma cells. Chondrogenic marker expression of bone marrow mesenchymal stem cells decreased slightly but not significantly. osteoarthritis and extracellular matrix markers of healthy and osteoarthritic chondrocytes at seven days in culture remained unchanged. In conclusion, GA-PEG@ nano(HA) composites had limited effects on mesenchymal stem cells, healthy and osteoarthritic chondrocytes.WoSScopu
The effect of colchicine on pyrin and pyrin interacting proteins.
No full textMEFV which encodes pyrin, cause familial Mediterranean fever (FMF), the most common auto-inflammatory disease. Pyrin is believed to be a regulator of inflammation, though the nature of this regulatory activity remains to be identified. Prophylactic treatment with colchicine, a microtubule toxin, has had a remarkable effect on disease progression and outcome. It has been thought that, inhibition of microtubule polymerization is the main mechanism of action of colchicine. But, the exact cellular mechanism explaining the efficacy of colchicine in suppressing FMF attacks is still unclear. Given the ability of colchicine treatment to be considered as a differential diagnosis criteria of FMF, we hypothesized that colchicine may have a specific effect on pyrin and pyrin interacting proteins. This study showed that colchicine prevents reticulated fibrils formed by PSTPIP1 filaments and reduces ASC speck rates in transfected cells. We further noted that, colchicine down-regulates MEFV expression in THP-1 cells. We also observed that colchicine causes re-organization of actin cytoskeleton in THP-1 cells. Pyrin is an actin-binding protein that specifically localizes with polymerizing actin filaments. Thus, MEFV expression might be affected by re-organization of actin cytoskeleton. The data presented here reveal an important connection between colchicine and pyrin which might explain the remarkable efficacy of colchicine in preventing FMF attacks. J. Cell. Biochem. 113: 35363546, 2012. (C) 2012 Wiley Periodicals, Inc
C1q deficiency: identification of a novel missense mutation and treatment with fresh frozen plasma
No full textA Turkish patient with C1q deficiency presented with a lupus-like disease, and a new missense mutation at A chain is presented. To characterize the genetic defect, all exons of the genes for the A, B, and C chains of C1q were sequenced in the patient. This revealed a missense mutation in the collagen-like domain of the A chain, p.Gly31Arg. No other sequence variants, including the common silent mutations, were found in the three chains. Exon 1 of the C1q A chain was sequenced in 105 samples from healthy controls for this particular mutation. None of these carried the mutation. The C1q-deficient patient was treated with fresh frozen plasma infusions. Our findings showed that Turkish patients may have different mutations than the previously described common mutation, and once again, not only nonsense mutations but also missense mutations cause hereditary C1q deficiency. Regular fresh frozen plasma infusions to the patient have been clinically and therapeutically successful
De novo cloning and functional characterization of potassium channel genes and proteins in the crayfish Astacus leptodactylus (Eschscholtz, 1823) (Decapoda: Astacidea: Astacidae)
No full textCurrent knowledge about the molecular properties of the crustacean ion channels is rather limited even if crustaceans have been widely used as a model in neuroscience. We cloned for the first time two different potassium channel genes from the freshwater crayfish Astacus leptodactylus (), one of the genes functionally expressed in the Xenopus oocytes. The open-reading frames of the genes were 1,203 and 3,447 bp, respectively. The nucleic acid sequence of the genes and associated proteins were similar to those of a typical potassium channel. BLAST analyses indicated that one of the cloned genes had a substantial similarity to an inward-rectifier potassium channel whereas the other gene was similar to a high-conductance-KCa type potassium channel reported in related species. Transmembrane topology and three-dimensional structure of the coded proteins were calculated and functional regions of the channel proteins responsible for ion selectivity, voltage sensing, gating, and calcium binding were identified. One of the cloned channel genes has been expressed in the Xenopus oocytes. Analysis of the expressed potassium currents confirmed that the cloned gene was coding a typical Kir-type potassium channel with ATP sensitivity
