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Yu, Wan-cheng, Hai-ying Chen, Hong-li Yang, Peng Xia, Cheng-wei Zou, Tong-wen Sun, and Le-xin Wang. "rBMSC/Cav-1F92A Mediates Oxidative Stress in PAH Rat by Regulating SelW/14-3-3η and CA1/Kininogen Signal Transduction." Stem Cells International 2019 (October 28, 2019): 1–11. http://dx.doi.org/10.1155/2019/6768571.
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Background/Objectives. Carbonic anhydrase 1 (CA1)/kininogen and selenoprotein W (SelW)/14-3-3η signal transduction orchestrate oxidative stress, which can also be regulated by nitric oxide (NO). The mutated caveolin-1 (Cav-1F92A) gene may enhance NO production. This study explored the effect of Cav-1F92A-modified rat bone marrow mesenchymal stem cells (rBMSC/Cav-1F92A) on oxidative stress regulation through CA1/kininogen and SelW/14-3-3η signal transduction in a rat model of monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH). Method. PAH was induced in rats through the subcutaneous injection of MCT. Next, rBMSC/Vector (negative control), rBMSC/Cav-1, rBMSC/Cav-1F92A, or rBMSC/Cav-1F92A+L-NAME were administered to the rats. Changes in pulmonary hemodynamic and vascular morphometry and oxidative stress levels were evaluated. CA1/kininogen and SelW/14-3-3η signal transduction, endothelial nitric oxide synthase (eNOS) dimerization, and eNOS/NO/sGC/cGMP pathway changes were determined through real-time polymerase chain reaction, Western blot, or immunohistochemical analyses. Results. In MCT-induced PAH rats, rBMSC/Cav-1F92A treatment reduced right ventricular systolic pressure, vascular stenosis, and oxidative stress; downregulated CA1/kininogen signal transduction; upregulated SelW/14-3-3η signal transduction; and reactivated the NO pathway. Conclusions. In a rat model of MCT-induced PAH, rBMSC/Cav-1F92A reduced oxidative stress by regulating CA1/kininogen and SelW/14-3-3η signal transduction.
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Merlini, L. "Familial isolated hyperCKaemia associated with a new mutation in the caveolin-3 (CAV-3) gene." Journal of Neurology, Neurosurgery & Psychiatry 73, no. 1 (July 1, 2002): 65–67. http://dx.doi.org/10.1136/jnnp.73.1.65.
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Tekin, Hande, and Pınar Edem. "CAV-3-related age-dependent muscle diseases: A novel mutation in mother and son." Neurology Asia 28, no. 3 (September 2023): 751–55. http://dx.doi.org/10.54029/2023scy.
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The caveolin-3 protein encoded by the CAV-3 gene is a muscle-specific protein found in skeletal, smooth, and cardiac muscle. Caveolin-3 defects lead to several muscle diseases: rippling muscle disease (RMD), limb-girdle muscular dystrophy (LGMD1C), distal myopathy, familial hypertrophic cardiomyopathy, and asymptomatic hyper-CK-emia. While some variants that cause mutations in this gene cause a pure type of disease, some variants may appear as overlap syndromes. Even in the same variants of CAV-3 mutation, the type of muscle disease, its severity, and time of occurrence can be variable. For this reason, it should be known that CAV-3-related diseases and all overlapping diseases can be seen over time, and the patient should be followed up. We report here a 9-year- old boy and his 38-year-old mother who were investigated for asymptomatic hyper-CK-emia and diagnosed with caveolinopathy. The boy had calf hypertrophy and percussion-induced rapid muscle contraction (PIRCs). His mother had calf hypertrophy, contractions due to percussion, and proximal muscle weakness. Mother’s proximal muscles and m. gastrocnemius magnetic resonance imaging (MRI) was normal. The mother had complaints of weakness, showing slow progression starting from the second decade. Heterozygous (ENST000003cav3849.2) c.298A>T p.Ile100Phe variant in exon 2 was detected in the CAV-3 gene. This mutation is classified as pathogenic according to The American College of Medical Genetics and Genomics (ACMG) criteria (PM1, PM2, PP3, PM5). In conclusion, calves’ pseudohypertrophy and mildly raised CK without weakness can be the initial presentation of caveolinopathy. Percussion-induced muscle contractions, rather than muscle rippling, can occur at a young age. The onset of muscle weakness can be delayed during adolescence and can have a slowly deteriorating course associated with myalgia.
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Kalinowski, M., Ł. Adaszek, P. Miłoszowska, M. Skrzypczak, A. Ziętek-Barszcz, J. Kutrzuba, Z. Grądzki, and S. Winiarczyk. "Molecular analysis of a fragment of gene E1B 19K of canine adenovirus 2 (CAV-2) isolated from dogs with symptoms of cough." Polish Journal of Veterinary Sciences 15, no. 3 (October 1, 2012): 425–30. http://dx.doi.org/10.2478/v10181-012-0066-7.
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AbstractThe aim of this study was to perform molecular analysis of canine adenovirus 2 (CAV-2) E1B 19K gene fragment isolated from 20 dogs of various breeds (12 males and 8 females aged 1-9 years), with clinical symptoms of upper respiratory tract infections, from the Lubelszczyzna region. Nasal swabs were taken from dogs. DNA of CAV-2 was detected using the PCR method in 16 swabs. All PCR products were sequenced, and the obtained sequences were compared with each other and with the sequence of the E1B 19K gene of the CAV-2 strain from an online database of NCBI GenBank: AC 000003. Based on analysis of the obtained sequences, three polymorphic variants of CAV-2 (No.1-3) with homology of 78 - 100% were distinguished. The nucleotide and amino acid sequences of the most frequently represented polymorphic variant, No. 1, differed from the sequences of polymorphic variant No. 2 with one substitution. The nucleotide and amino acid sequence of the E1B 19K gene of CAV-2 AC 000003 differed from the analogous sequences of representatives of variant No. 1 with 44 nucleotide and 19 amino acid substitutions. The small number of nucleotide differences in the E1B 19K CAV-2 gene among the examined own isolates, compared with AC 000003, suggest that the infections in dogs were caused by a relatively genetically stable virus which occurs in eastern Poland.
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Szelechowski, Marion, Annie Fournier, Jennifer Richardson, Marc Eloit, and Bernard Klonjkowski. "Functional organization of the major late transcriptional unit of canine adenovirus type 2." Journal of General Virology 90, no. 5 (May 1, 2009): 1215–23. http://dx.doi.org/10.1099/vir.0.007773-0.
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Vectors derived from canine adenovirus type 2 (CAV-2) are attractive candidates for gene therapy and live recombinant vaccines. CAV-2 vectors described thus far have been generated by modifying the virus genome, most notably early regions 1 and 3 or the fiber gene. Modification of these genes was underpinned by previous descriptions of their mRNA and protein-coding sequences. Similarly, the construction of new CAV-2 vectors bearing changes in other genomic regions, in particular many of those expressed late in the viral cycle, will require prior characterization of the corresponding transcriptional units. In this study, we provide a detailed description of the late transcriptional organization of the CAV-2 genome. We examined the major late transcription unit (MLTU) and determined its six families of mRNAs controlled by the putative major late promoter (MLP). All mRNAs expressed from the MLTU had a common non-coding tripartite leader (224 nt) at their 5′ end. In transient transfection assays, the predicted MLP sequence was able to direct luciferase gene expression and the TPL sequence yielded a higher amount of transgene product. Identification of viral transcriptional products following in vitro infection confirmed most of the predicted protein-coding regions that were deduced from computer analysis of the CAV-2 genome. These findings contribute to a better understanding of gene expression in CAV-2 and lay the foundation required for genetic modifications aimed at vector optimization.
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He, Miaomiao, Jie Qiu, Yan Wang, Yang Bai, and Guangzhi Chen. "Caveolin-3 and Arrhythmias: Insights into the Molecular Mechanisms." Journal of Clinical Medicine 11, no. 6 (March 14, 2022): 1595. http://dx.doi.org/10.3390/jcm11061595.
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Caveolin-3 is a muscle-specific protein on the membrane of myocytes correlated with a variety of cardiovascular diseases. It is now clear that the caveolin-3 plays a critical role in the cardiovascular system and a significant role in cardiac protective signaling. Mutations in the gene encoding caveolin-3 cause a broad spectrum of clinical phenotypes, ranging from persistent elevations in the serum levels of creatine kinase in asymptomatic humans to cardiomyopathy. The influence of Caveolin-3(CAV-3) mutations on current density parallels the effect on channel trafficking. For example, mutations in the CAV-3 gene promote ventricular arrhythmogenesis in long QT syndrome 9 by a combined decrease in the loss of the inward rectifier current (IK1) and gain of the late sodium current (INa-L). The functional significance of the caveolin-3 has proved that caveolin-3 overexpression or knockdown contributes to the occurrence and development of arrhythmias. Caveolin-3 overexpression could lead to reduced diastolic spontaneous Ca2+ waves, thus leading to the abnormal L-Type calcium channel current-induced ventricular arrhythmias. Moreover, CAV-3 knockdown resulted in a shift to more negative values in the hyperpolarization-activated cyclic nucleotide channel 4 current (IHCN4) activation curve and a significant decrease in IHCN4 whole-cell current density. Recent evidence indicates that caveolin-3 plays a significant role in adipose tissue and is related to obesity development. The role of caveolin-3 in glucose homeostasis has attracted increasing attention. This review highlights the underlining mechanisms of caveolin-3 in arrhythmia. Progress in this field may contribute to novel therapeutic approaches for patients prone to developing arrhythmia.
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Pallister, Jackie, Kevin J. Fahey, and Michael Sheppard. "Cloning and sequencing of the chicken anaemia virus (CAV) ORF-3 gene, and the development of an ELISA for the detection of serum antibody to CAV." Veterinary Microbiology 39, no. 1-2 (March 1994): 167–78. http://dx.doi.org/10.1016/0378-1135(94)90097-3.
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Robinson, J. M. "What Can Epitope Specific Antibodies Tell us About the Organization of Caveolin in Cells?" Microscopy and Microanalysis 7, S2 (August 2001): 1030–31. http://dx.doi.org/10.1017/s1431927600031226.
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There are three members of the caveolin (CAV) gene family that give rise to four polypeptides. These polypeptides are CAV-1α, CAV-1β, CAV-2, and CAV-3. The CAV-1β isoform is a truncated form of CAV-1α that lacks 31 amino acids at the N-terminus of the molecule. The CAV- 1β molecule arises through an alternative splicing mechanism.Caveolae are specialized plasma membrane microdomains that are expressed at high levels in some cell types (e.g., endothelium, adipocytes, fibroblasts). These specialized regions of the plasma membrane have a characteristic omega-shaped appearance with diameters ranging from 40-90 run. They are distinct from clathrin-coated pits since they lack the characteristic coated appearance in electron microscopy. Caveolae were among the first structures to be discovered by biological electron microscopy. However, biochemical characterization of these structures did not begin in earnest until a marker protein was identified. The initial marker was the 22-kDa protein known as caveolin.
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Smuts, Heidi E. M. "Novel Gyroviruses, including Chicken Anaemia Virus, in Clinical and Chicken Samples from South Africa." Advances in Virology 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/321284.
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Introduction. Chicken anaemia virus, CAV, was until recently the only member of theGyrovirusgenus. 6 novel gyroviruses, AGV2, HGyV1, and GyV3-6, have since been discovered in human and chicken samples.Methods. PCR amplification of the VP2 gene was used to detect AGV2/HGyV1, GyV3, and CAV in a range of clinical samples including stool, respiratory, CSF, and HIV-positive plasma. Screening of fresh local chicken meat was also performed.Results. AGV2/HGyV1 or GyV3 was detected in stools from healthy children (17/49, 34.7%) and patients with diarrhoea (22/149, 14.8%). 1.2% (3/246) nasopharyngeal respiratory samples were positive. No AGV2/HGyV1 or GyV3 was detected in nasal swabs from wheezing patients, in CSF from patients with meningitis, and in HIVpositive plasma. CAV was found in 51% (25/49) of stools from healthy children and 16% (24/149) in diarrhoea samples. Screening of 28 chicken samples showed a higher prevalence of gyrovirus (20/28, 71%) compared to CAV (1/28, 3.6%). Phylogenetic analysis of the CAV VP1 gene showed South African sequences clustering with Brazilian isolates from genotypes D2 and A2.Conclusion. Novel gyroviruses, including CAV, are present in the South African population with diarrhoea and respiratory illness as well as in healthy children. Their presence suggests an origin from chicken meat consumption.
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Nogueira, E. O., L. Brentano, and A. J. P. Ferreira. "A VP3/VP1 gene polymerase chain reaction assay for detection of chicken anemia virus in broiler samples." Arquivo Brasileiro de Medicina Veterinária e Zootecnia 57, suppl 2 (September 2005): 131–40. http://dx.doi.org/10.1590/s0102-09352005000800001.
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A PCR assay was designed for amplification of the highly conserved VP3 gene and a 5' region of the VP1 gene, for the diagnosis of CAV in organ samples of broiler flocks suspected of chicken infectious anemia. A comparison of the VP3/VP1 PCR with in vivo virus isolation revealed 100% agreement of the results, with 13 positive and 3 negative samples in both assays, indicating that the VP3/VP1 PCR is a specific diagnostic method. Tissues from additional 24 broiler chicken flocks, with CAV-like lesions and clinical history were then tested only by the VP3/VP1 PCR and a reference PCR with published primers for the VP1 gene. Nineteen samples resulted positive and one negative in both PCR, while another 4 samples were positive only in the VP3/VP1 PCR. These results indicate that the VP3/VP1 PCR is a sensitive, specific diagnostic test, suitable as an alternative to the expensive and time consuming in vivo virus isolation method, specially considering the difficult diagnosis of CAV strains not readily adaptable to MSB-1 cell culture.
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CHITRADEVI, S., K. SUKUMAR, P. SURESH, G. A. BALASUBRAMANIAM, and D. KANNAN. "Molecular typing of fowl adenovirus associated with gizzard erosion in commercial layer grower chicken in Tamil Nadu." Indian Journal of Animal Sciences 90, no. 7 (October 29, 2020): 977–81. http://dx.doi.org/10.56093/ijans.v90i7.106664.
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The present study was undertaken to characterize fowl adenovirus associated with commercial layer grower chicken showed gizzard erosion. Ninety four commercial layer grower chicken flocks from Namakkal districts of Tamil Nadu had shown reduced feed intake, reduced weight gain, uneven growth and mortality of 0.3 to 7.7%. On postmortem examination of affected birds showed mild to severe gizzard erosion, blackish discoloration of gizzard contents, pale liver and no major lesions were seen in other organs. Total DNA was extracted and 897 bp fowl adenovirus specific hexon gene was amplified by PCR. Out of 94 flocks screened seven flocks were found positive of fowl adenovirus. Chicken embryo liver cell culture was prepared to isolate field fowl adenovirus from suspected flocks. Concurrent infection of chicken anaemia virus (CAV) was also screened by PCR for 419 bp VP2 gene of CAV and found that all the seven flocks which were PCR positive for FAdV also found positive for CAV. Sequencing and phylogenetic analysis of 897 bp FAdV hexon gene revealed that, it was belonged to FAdV serotypes 2 and 3 of species D.
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Engelman, Jeffrey A., Xiao Lan Zhang, Ferruccio Galbiati, and Michael P. Lisanti. "Chromosomal localization, genomic organization, and developmental expression of the murine caveolin gene family (Cav-1, -2, and -3)." FEBS Letters 429, no. 3 (June 16, 1998): 330–36. http://dx.doi.org/10.1016/s0014-5793(98)00619-x.
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Williams, Terence M., Michelle W. C. Cheung, David S. Park, Babak Razani, Alex W. Cohen, William J. Muller, Dolores Di Vizio, Neeru G. Chopra, Richard G. Pestell, and Michael P. Lisanti. "Loss of Caveolin-1 Gene Expression Accelerates the Development of Dysplastic Mammary Lesions in Tumor-Prone Transgenic Mice." Molecular Biology of the Cell 14, no. 3 (March 2003): 1027–42. http://dx.doi.org/10.1091/mbc.e02-08-0503.
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Caveolin-1 is the principal structural component of caveolae microdomains, which represent a subcompartment of the plasma membrane. Several independent lines of evidence support the notion that caveolin-1 functions as a suppressor of cell transformation. For example, the human CAV-1 gene maps to a suspected tumor suppressor locus (D7S522/7q31.1) that is frequently deleted in a number of carcinomas, including breast cancers. In addition, up to 16% of human breast cancers harbor a dominant-negative mutation, P132L, in the CAV-1 gene. Despite these genetic associations, the tumor suppressor role of caveolin-1 still remains controversial. To directly assess the in vivo transformation suppressor activity of the caveolin-1 gene, we interbred Cav-1 (−/−) null mice with tumor-prone transgenic mice (MMTV-PyMT) that normally develop multifocal dysplastic lesions throughout the entire mammary tree. Herein, we show that loss of caveolin-1 gene expression dramatically accelerates the development of these multifocal dysplastic mammary lesions. At 3 wk of age, loss of caveolin-1 resulted in an approximately twofold increase in the number of lesions (foci per gland; 3.3 ± 1.0 vs. 7.0 ± 1.2) and an approximately five- to sixfold increase in the total area occupied by these lesions. Similar results were obtained at 4 wk of age. However, complete loss of caveolin-1 was required to accelerate the appearance of these dysplastic mammary lesions, because Cav-1 (+/−) heterozygous mice did not show any increases in foci development. We also show that loss of caveolin-1 increases the extent and the histological grade of these mammary lesions and facilitates the development of papillary projections in the mammary ducts. Finally, we demonstrate that cyclin D1 expression levels are dramatically elevated in Cav-1 (−/−) null mammary lesions, consistent with the accelerated appearance and growth of these dysplastic foci. This is the first in vivo demonstration that caveolin-1 can function as a transformation suppressor gene.
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Keriel, Anne, Céline René, Chad Galer, Joseph Zabner, and Eric J. Kremer. "Canine Adenovirus Vectors for Lung-Directed Gene Transfer: Efficacy, Immune Response, and Duration of Transgene Expression Using Helper-Dependent Vectors." Journal of Virology 80, no. 3 (February 1, 2006): 1487–96. http://dx.doi.org/10.1128/jvi.80.3.1487-1496.2006.
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ABSTRACT A major hurdle to the successful clinical use of some viral vectors relates to the innate, adaptive, and memory immune responses that limit the efficiency and duration of transgene expression. Some of these drawbacks may be circumvented by using vectors derived from nonhuman viruses such as canine adenovirus type 2 (CAV-2). Here, we evaluated the potential of CAV-2 vectors for gene transfer to the respiratory tract. We found that CAV-2 transduction was efficient in vivo in the mouse respiratory tract, and ex vivo in well-differentiated human pulmonary epithelia. Notably, the in vivo and ex vivo efficiency was poorly inhibited by sera from mice immunized with a human adenovirus type 5 (HAd5, a ubiquitous human pathogen) vector or by human sera containing HAd5 neutralizing antibodies. Following intranasal instillation in mice, CAV-2 vectors also led to a lower level of inflammatory cytokine secretion and cellular infiltration compared to HAd5 vectors. Moreover, CAV-2 transduction efficiency was increased in vitro in human pulmonary cells and in vivo in the mouse respiratory tract by FK228, a histone deacetylase inhibitor. Finally, by using a helper-dependent CAV-2 vector, we increased the in vivo duration of transgene expression to at least 3 months in immunocompetent mice without immunosuppression. Our data suggest that CAV-2 vectors may be efficient and safe tools for long-term clinical gene transfer to the respiratory tract.
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Shahzad, Khurram, Martin Cadeiras, Sarfaraz Memon, Barry Zeeberg, Tod Klingler, Anshu Sinha, Esteban G. Tabak, Sreevalsa Unniachan, and Mario C. Deng. "Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy." Journal of Transplantation 2010 (2010): 1–13. http://dx.doi.org/10.1155/2010/719696.
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Background. Cardiac allograft vasculopathy (CAV) is a major cause of graft loss and death after heart transplantation. Currently, no diagnostic methods are available during the early post-transplant period to accurately identify patients at risk of CAV. We hypothesized that PBMC gene expression profiles (GEP) can identify patients at risk of CAV.Methods. We retrospectively analyzed a limited set of whole-genome PBMC microarrays from 10 post-transplant patients who did (n=3) or did not (n=7) develop advanced grade CAV during their long-term follow-up. We used significance analysis of microarrays to identify differentially expressed genes and High-Throughput GoMiner to assess gene ontology (GO) categories. We corroborated our findings by retrospective analysis of PBMC real-time PCR data from 33 patients.Results. Over 300 genes were differentially expressed (FDR < 5%), and 18 GO-categories including “macrophage activation”, “Interleukin-6 pathway”, “NF-KappaB cascade”, and “response to virus” were enriched by these genes (FDR < 5%). Out of 8 transcripts available for RT-PCR analysis, we confirmed 6 transcripts (75.0%) including FPRL1, S100A9, CXCL10, PRO1073, and MMP9 (P<.05).Conclusion. Our pilot data suggest that GEP of PBMC may become a valuable tool in the evaluation of patients at risk of CAV. Larger prospectively designed studies are needed to corroborate our hypothesis.
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Caeiro, André, Sandra Caeiro, Sandra Correia, and Jorge Canhoto. "Induction of Somatic Embryogenesis in Tamarillo (Solanum betaceum Cav.) Involves Increases in the Endogenous Auxin Indole-3-Acetic Acid." Plants 11, no. 10 (May 19, 2022): 1347. http://dx.doi.org/10.3390/plants11101347.
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Somatic embryogenesis (SE) is a complex biological process regulated by several factors, such as the action of plant growth regulators, namely auxins, of which the most physiologically relevant is indole-3-acetic acid (IAA). In tamarillo, an optimized system for induction of SE creates, after an induction process, embryogenic (EC) and non-embryogenic callus (NEC). In this work the endogenous levels of auxin along the induction phase and in the calli samples were investigated using chemical quantifications by colorimetric reactions and HPLC as well as immunohistochemistry approaches. Differential gene expression (IAA 11, IAA 14, IAA 17, TIR 1, and AFB3) analysis during the induction phase was also carried out. The results showed that the endogenous IAA content is considerably higher in embryogenic than in non-embryogenic calli, with a tendency to increase as the dedifferentiation of the original explant (leaf segments) evolves. Furthermore, the degradation rates of IAA seem to be related to these levels, as non-embryogenic tissue presents a higher degradation rate. The immunohistochemical results support the quantifications made, with higher observable labeling on embryogenic tissue that tends to increase along the induction phase. Differential gene expression also suggests a distinct molecular response between EC and NEC.
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Hassan, Ghada S., Terence M. Williams, Philippe G. Frank, and Michael P. Lisanti. "Caveolin-1-deficient aortic smooth muscle cells show cell autonomous abnormalities in proliferation, migration, and endothelin-based signal transduction." American Journal of Physiology-Heart and Circulatory Physiology 290, no. 6 (June 2006): H2393—H2401. http://dx.doi.org/10.1152/ajpheart.01161.2005.
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We previously showed that ablation of caveolin-1 (Cav-1) gene expression in mice promotes neointimal hyperplasia in vivo, a phenomenon normally characterized by smooth muscle cell (SMC) migration and proliferation. Whether these defects are cell autonomous, i.e., due to loss of Cav-1 within SMCs or loss of Cav-1 expression in other adjacent cell types in vivo, remains unknown. Cav-1 has been shown to associate with receptors for many vasoactive factors on the SMC surface. Therefore, Cav-1 might be an important regulator of SMC proliferation, migration, and signal transduction. To mechanistically dissect the role of Cav-1 in SMC signaling, we isolated SMCs from the aortas (AoSMCs) of Cav-1-deficient (Cav-1−/−) mice and characterized these cells with respect to their proliferation, migration, and Ca2+ response to an important vasoactive factor, endothelin-1 (ET-1). 5-Bromo-2′-deoxyuridine incorporation and a wound-healing assay showed an increase in proliferation and migration rates in Cav-1−/− compared with wild-type (Cav-1+/+) AoSMCs. Cav-1−/− AoSMCs demonstrated upregulation of phosphorylated ERK1/2, cyclin D1, and proliferating cell nuclear antigen and reduced expression of the cyclin-dependent kinase inhibitor p27 Kip1. The Ca2+ response was examined in the presence of ET-1 and assessed by confocal microscopy with the Ca2+-sensitive fluorescent probe fluo 3. When treated with ET-1, Cav-1−/− AoSMCs exhibited a faster and larger increase in free intracellular Ca2+ than Cav-1+/+ cells. The ET-1-induced response in Cav-1−/− cells was mediated by the ETB receptor, as shown using the ETB receptor antagonist BQ-788 and the ETA receptor antagonist BQ-123. In Cav-1−/− cells, ETA receptor expression was reduced and ETB receptor expression was upregulated. Therefore, Cav-1 ablation increased the ET-1-induced Ca2+ response in SMCs by altering the type and expression level of the ET receptor (i.e., receptor isoform switching). These data suggest a novel regulatory role for Cav-1 in SMCs with respect to their proliferation, migration, and Ca2+-mediated signaling.
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Almejhim, Mariam, Mohammed Aljeldah, and Nasreldin Elhadi. "Improved isolation and detection of toxigenic Vibrio parahaemolyticus from coastal water in Saudi Arabia using immunomagnetic enrichment." PeerJ 9 (October 29, 2021): e12402. http://dx.doi.org/10.7717/peerj.12402.
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Background Vibrio parahaemolyticus is recognized globally as a cause of foodborne gastroenteritis and its widely disseminated in marine and coastal environment throughout the world. The main aim of this study was conducted to investigate the presence of toxigenic V. parahaemolyticus in costal water in the Eastern Province of Saudi Arabia by using immunomagnetic separation (IMS) in combination with chromogenic Vibrio agar medium and PCR targeting toxR gene of species level and virulence genes. Methods A total of 192 seawater samples were collected from five locations and enriched in alkaline peptone water (APW) broth. One-milliliter portion from enriched samples in APW were mixed with an immunomagnetic beads (IMB) coated with specific antibodies against V. parahaemolyticus polyvalent K antisera and separated beads with captured bacteria streaked on thiosulfate citrate bile salts sucrose (TCBS) agar and CHROMagar Vibrio (CaV) medium. Results Of the 192 examined seawater samples, 38 (19.8%) and 44 (22.9%) were positive for V. parahaemolyticus, producing green and mauve colonies on TCBS agar and CaV medium, respectively. Among 120 isolates of V. parahaemolyticus isolated in this study, 3 (2.5%) and 26 (21.7%) isolates of V. parahaemolyticus isolated without and with IMB treatment tested positive for the toxin regulatory (toxR) gene, respectively. Screening of the confirmed toxR gene-positive isolates revealed that 21 (17.5%) and 3 (2.5%) were positive for the thermostable direct hemolysin (tdh) encoding gene in strains isolated with IMB and without IMB treatment, respectively. None of the V. parahaemolyticus strains tested positive for the thermostable related hemolysin (trh) gene. In this study, we found that the CaV medium has no advantage over TCBS agar if IMB concentration treatment is used during secondary enrichment steps of environmental samples. The enterobacterial repetitive intergenic consensus (ERIC)-PCR DNA fingerprinting analysis revealed high genomic diversity, and 18 strains of V. parahaemolyticus were grouped and identified into four identical ERIC clonal group patterns. Conclusions The presented study reports the first detection of tdh producing V. parahaemolyticus in coastal water in the Eastern Province of Saudi Arabia.
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Singh, Dhirendra Pratap, Rashmi Pathak, Abhishek Pandit, Philip J. Ebenezer, Nithya Jambunathan, Sanjay Kumar, Alexander Du Plooy, Joseph Francis, and Mary E. White. "Abstract 3604: Epithelial Caveolin-1 regulates lung metastasis in advanced stages of breast cancer." Cancer Research 83, no. 7_Supplement (April 4, 2023): 3604. http://dx.doi.org/10.1158/1538-7445.am2023-3604.
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Abstract Organotypic metastasis is a well-orchestrated sequence of events that takes place in tumors. The interplay between secretory factors from the primary tumor and the microenvironment of a distant organ determines the fate of metastasis. A significant concern in effective triple-negative breast cancer (TNBC) treatment is lung metastasis. Caveolin-1 (Cav-1), a lipid raft protein, is an important component of the metastatic interplay and is reported to be upregulated in the advanced metastatic stage of breast cancer. Although Cav-1 has been shown to have oncogenic potential, its role in TNBC lung metastasis is not fully understood. Our data illustrates, knocking out Cav-1 in the 4T1 cells (a mouse breast cancer cell line) affects cell morphology, extracellular vesicle formation, and MMP release in vitro. Furthermore, a wound healing/cell migration assay showed reduced migration in Cav-1 KO 4T1 cells when compared to control 4T1 cells, and these findings were validated using Cav-1 siRNA. For investigating the metastatic role, we injected Cav-1 KO 4T1 and control 4T1 cells into the mammary fat pad of female BALB/c mice, a syngeneic mouse model of triple-negative breast cancer. We found no evidence of lung metastasis in Cav-1 KO 4T1 injected mice when compared to control 4T1 injected mice. This was further supported by mRNA profiling of the tumor. We observed 21 epithelial cell migration genes that are differentially expressed in Cav-1 KO tumors when compared to WT tumors. Correlation analysis from Breast Cancer Gene-Expression Miner v4.8 (bc-GenExMiner), a human database, showed a significant correlation between Cav-1 expression and several of the 21 epithelial cell migration genes, along with integrin 3 alpha (ITGα3). Interestingly, in silico protein docking predicted an interaction between Cav-1 and ITGα3, which was later confirmed by co-immunoprecipitation. The role of ITGα3 in metastasis was further corroborated by cell migration assay, which was affected when siRNA was used to silence ITGα3 gene expression. Collectively, these findings provide evidence that Cav-1 KO, along with ITGa3, plays an important role in distant lung metastasis in the 4T1 tumor-induced mice model. Citation Format: Dhirendra Pratap Singh, Rashmi Pathak, Abhishek Pandit, Philip J. Ebenezer, Nithya Jambunathan, Sanjay Kumar, Alexander Du Plooy, Joseph Francis, Mary E. White. Epithelial Caveolin-1 regulates lung metastasis in advanced stages of breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3604.
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Kikuchi, Tateki. "Caveolin-3: A Causative Process of Chicken Muscular Dystrophy." Biomolecules 10, no. 9 (August 20, 2020): 1206. http://dx.doi.org/10.3390/biom10091206.
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The etiology of chicken muscular dystrophy is the synthesis of aberrant WW domain containing E3 ubiquitin-protein ligase 1 (WWP1) protein made by a missense mutation of WWP1 gene. The β-dystroglycan that confers stability to sarcolemma was identified as a substrate of WWP protein, which induces the next molecular collapse. The aberrant WWP1 increases the ubiquitin ligase-mediated ubiquitination following severe degradation of sarcolemmal and cytoplasmic β-dystroglycan, and an erased β-dystroglycan in dystrophic αW fibers will lead to molecular imperfection of the dystrophin-glycoprotein complex (DGC). The DGC is a core protein of costamere that is an essential part of force transduction and protects the muscle fibers from contraction-induced damage. Caveolin-3 (Cav-3) and dystrophin bind competitively to the same site of β-dystroglycan, and excessive Cav-3 on sarcolemma will block the interaction of dystrophin with β-dystroglycan, which is another reason for the disruption of the DGC. It is known that fast-twitch glycolytic fibers are more sensitive and vulnerable to contraction-induced small tears than slow-twitch oxidative fibers under a variety of diseased conditions. Accordingly, the fast glycolytic αW fibers must be easy with rapid damage of sarcolemma corruption seen in chicken muscular dystrophy, but the slow oxidative fibers are able to escape from these damages.
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Courtaut, Flavie, Alessandra Scagliarini, Virginie Aires, Clarisse Cornebise, Jean-Paul Pais de Barros, Céline Olmiere, and Dominique Delmas. "VEGF-R2/Caveolin-1 Pathway of Undifferentiated ARPE-19 Retina Cells: A Potential Target as Anti-VEGF-A Therapy in Wet AMD by Resvega, an Omega-3/Polyphenol Combination." International Journal of Molecular Sciences 22, no. 12 (June 19, 2021): 6590. http://dx.doi.org/10.3390/ijms22126590.
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Age-related macular degeneration (AMD) is one of the main causes of deterioration in vision in adults aged 55 and older. In spite of therapies, the progression of the disease is often observed without reverse vision quality. In the present study, we explored whether, in undifferentiated ARPE-19 retinal cells, a disruption of the VEGF receptors (VEGF-R)/caveolin-1 (Cav-1)/protein kinases pathway could be a target for counteracting VEGF secretion. We highlight that Resvega®, a combination of omega-3 fatty acids with an antioxidant, resveratrol, inhibits VEGF-A secretion in vitro by disrupting the dissociation of the VEGF-R2/Cav-1 complex into rafts and subsequently preventing MAPK activation. Moreover, DNA ChIP analysis reveals that this combination prevents the interaction between AP-1 and vegf-a and vegf-r2 gene promoters. By these pathways, Resvega could present a potential interest as nutritional complementation against AMD.
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Zhang, Dongxu, Wenyu Du, Xingming Pan, Xiaoxu Lin, Fang-Ru Li, Qingling Wang, Qian Yang, Hui-Min Xu, and Liao-Bin Dong. "Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus." Beilstein Journal of Organic Chemistry 20 (April 16, 2024): 815–22. http://dx.doi.org/10.3762/bjoc.20.73.
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Drimane-type sesquiterpenoids (DMTs) are characterized by a distinctive 6/6 bicyclic skeleton comprising the A and B rings. While DMTs are commonly found in fungi and plants, their presence in bacteria has not been reported. Moreover, the biosynthetic pathways for DMTs have been primarily elucidated in fungi, with identified P450s only acting on the B ring. In this study, we isolated and characterized three bacterial DMTs, namely 3β-hydroxydrimenol (2), 2α-hydroxydrimenol (3), and 3-ketodrimenol (4), from Streptomyces clavuligerus. Through genome mining and heterologous expression, we identified a cav biosynthetic gene cluster responsible for the biosynthesis of DMTs 2–4, along with a P450, CavA, responsible for introducing the C-2 and C-3 hydroxy groups. Furthermore, the substrate scope of CavA revealed its ability to hydroxylate drimenol analogs. This discovery not only broadens the known chemical diversity of DMTs from bacteria, but also provides new insights into DMT biosynthesis in bacteria.
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Nunes, Cley Donizeti Martins, Monalize Salete Mota, Fernando Irajá Félix de Carvalho, and Antonio Costa de Oliveira. "Variabilidade de Pyricularia oryzae Cav. em genótipos de arroz." Pesquisa Agropecuária Tropical 44, no. 3 (September 2014): 263–70. http://dx.doi.org/10.1590/s1983-40632014000300014.
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A brusone, causada pelo fungo Pyricularia oryzae Cav., é uma das mais importantes doenças da cultura do arroz. O conhecimento das raças do fungo permite direcionar o melhoramento genético, visando ao desenvolvimento de cultivares resistentes. Este trabalho objetivou determinar a variabilidade do fungo e a prevalência de raças, em genótipos de arroz irrigado; avaliar as reações das linhagens quase isogênicas de CO 39 aos isolados de P. oryzae; e identificar os genótipos de arroz que possuem genes complementares de resistência a estes isolados. O estudo foi realizado com 36 isolados de P. oryzae, coletados em 18 cultivares de arroz irrigado, em quatro municípios do Rio Grande do Sul. Foram identificadas 21 raças, ocorrendo maior frequência das raças do grupo IA, em todos os locais de coleta, destacando-se, dentre elas, a IA-1. Reação de resistência foi observada nas cultivares BRS Firmeza, Bluebelle, Te-tep e BRS 7 (Taim) e de susceptibilidade em Fanny, Dawn, BRS Pelota e BRS Atalanta. A série de linhagens quase isogênicas obtidas da cultivar CO 39 foi resistente aos isolados na seguinte ordem: C101 A51 (resistente para todos os isolados); C101 PKT (12); C104PKT (11); C105HP4L23 (8); e C101-LAC (3). A partir do estudo destes isolados, concluiu-se que há variabilidade de P. oryzae, prevalência da raça IA, maior tolerância da cultivar BRS Firmeza e que o gene Pi-2 confere resistência à brusone, em todos os isolados analisados.
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Lee, Y. S., C. A. VandeVoort, and K. E. Latham. "188 EFFECTS OF IN VITRO MATURATION ON GENE EXPRESSION IN RHESUS MONKEY OOCYTES." Reproduction, Fertility and Development 21, no. 1 (2009): 193. http://dx.doi.org/10.1071/rdv21n1ab188.
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Assisted reproduction technologies (ARTs) are achieving increasing prominence in reproductive medicine. With the increasing application of ARTs comes increased interest in optimizing efficiency while minimizing potential risks to the offspring. One area of assisted reproduction in which improvements are being sought is in vitro oocyte maturation. In vitro oocyte maturation (IVM) holds great promise as a tool for enhancing clinical treatment of infertility, enhancing availability of non-human primates for development of disease models, and facilitating endangered species preservation. However, IVM outcomes have remained significantly below success rates obtained using in vivo-matured (VVM) oocytes from humans and non-human primates. There is thus considerable interest in improving IVM. Key objectives toward achieving more efficient IVM will be to establish the molecular determinants of oocyte quality, identify specific biological processes or mechanisms that may be disrupted by ARTs, and identify specific modifications to procedures to eliminate these deficiencies. This study provides the first global comparison of mRNA expression profiles between in vitro- and in vivo-matured metaphase II stage oocytes in a non-human primate species. RNAs isolated from oocytes of each kind (IVM and VVM) were subjected to a 2-cycle labeling assay, and the labeled cRNAs were hybridized to Affymetrix rhesus macaque genome arrays (Affymetrix Inc., Santa Clara, CA, USA). To minimize false positive signals, only genes called present in at least 3 out of 4 biological replicates were used for significance analysis of microarray. Genes with significant differences among samples were identified at the 5% false discovery rate and were further selected on the basis of t-test (P < 0.05). We observed a small set of just 59 mRNAs that are differentially expressed between the 2 types of oocytes. Independent confirmation of gene expression differences was performed for 19 candidate genes using the quantitative RT-PCR. Gene functional classification analysis revealed that genes differentially expressed between IVM and VVM oocytes are related to cellular homeostasis, cell-cell interactions including growth factor and hormone stimulation and cell adhesion, and other functions such as mRNA stability and translation. Additionally, we observed in IVM oocytes overexpression of PLAGL1 and MEST, 2 maternally imprinted genes, indicating a possible interruption or loss of correct epigenetic programming. These results provide novel insight into the nature of oocyte-follicle cell interactions, the potential molecular and cellular consequences of altering these interactions, and the basis for compromised developmental competence following IVM procedures in a non-human primate model. The results also raise concerns about applying IVM clinically without addressing such developmental defects but indicate that these deficiencies may be overcome by further improvement in IVM culture systems. This study was supported by grants from the National Institutes of Health, National Centers for Research Resources (NCRR) RR15253 (KEL), RR000169 (CAV), and RR13439 (CAV).
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Kucharski, Thomas J., Timothy F. Ng, David M. Sharon, Pedram Navid-Azarbaijani, Mahvash Tavassoli, and Jose G. Teodoro. "Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation Is Required for Apoptotic Activity and Efficient Viral Replication." Journal of Virology 90, no. 20 (August 10, 2016): 9433–45. http://dx.doi.org/10.1128/jvi.00936-16.
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ABSTRACTChicken anemia virus (CAV) is a single-stranded circular DNA virus that carries 3 genes, the most studied of which is the gene encoding VP3, also known as apoptin. This protein has been demonstrated to specifically kill transformed cells while leaving normal cells unharmed in a manner that is independent of p53 status. Although the mechanistic basis for this differential activity is unclear, it is evident that the subcellular localization of the protein is important for the difference. In normal cells, apoptin exists in filamentous networks in the cytoplasm, whereas in transformed cells, apoptin is present in the nucleus and appears as distinct foci. We have previously demonstrated that DNA damage signaling through the ataxia telangiectasia mutated (ATM) pathway induces the translocation of apoptin from the cytoplasm to the nucleus, where it induces apoptosis. We found that apoptin contains four checkpoint kinase consensus sites and that mutation of either threonine 56 or 61 to alanine restricts apoptin to the cytoplasm. Furthermore, treatment of tumor cells expressing apoptin with inhibitors of checkpoint kinase 1 (Chk1) and Chk2 causes apoptin to localize to the cytoplasm. Importantly, silencing of Chk2 rescues cancer cells from the cytotoxic effects of apoptin. Finally, treatment of virus-producing cells with Chk inhibitor protects them from virus-mediated toxicity and reduces the titer of progeny virus. Taken together, our results indicate that apoptin is a sensor of DNA damage signaling through the ATM-Chk2 pathway, which induces it to migrate to the nucleus during viral replication.IMPORTANCEThe chicken anemia virus (CAV) protein apoptin is known to induce tumor cell-specific death when expressed. Therefore, understanding its regulation and mechanism of action could provide new insights into tumor cell biology. We have determined that checkpoint kinase 1 and 2 signaling is important for apoptin regulation and is a likely feature of both tumor cells and host cells producing virus progeny. Inhibition of checkpoint signaling prevents apoptin toxicity in tumor cells and attenuates CAV replication, suggesting it may be a future target for antiviral therapy.
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Radmanić, Leona, Petra Korać, Lana Gorenec, Petra Šimičić, Kristian Bodulić, Adriana Vince, and Snježana Židovec Lepej. "Distinct Expression Patterns of Genes Coding for Biological Response Modifiers Involved in Inflammatory Responses and Development of Fibrosis in Chronic Hepatitis C: Upregulation of SMAD-6 and MMP-8 and Downregulation of CAV-1, CTGF, CEBPB, PLG, TIMP-3, MMP-1, ITGA-1, ITGA-2 and LOX." Medicina 58, no. 12 (November 27, 2022): 1734. http://dx.doi.org/10.3390/medicina58121734.
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Background and Objectives: The aim of this study was to analyze the expression of genes on transcriptomic levels involved in inflammatory immune responses and the development of fibrosis in patients with chronic hepatitis C. Materials and Methods: Expression patterns of 84 selected genes were analyzed with real-time quantitative RT PCR arrays in the peripheral blood of treatment-naive patients with chronic hepatitis C and healthy controls. The panel included pro- and anti-fibrotic genes, genes coding for extracellular matrix (EMC) structural constituents and remodeling enzymes, cell adhesion molecules, inflammatory cytokines, chemokines and growth factors, signal transduction members of the transforming growth factor- beta (TGF-ß) superfamily, transcription factors, and genes involved in epithelial to mesenchymal transition. Results: The expression of SMAD-6 coding for a signal transduction TGF-beta superfamily member as well as MMP-8 coding for an ECM protein were significantly increased in CHC patients compared with controls. Conclusions: Chronic hepatitis C was also characterized by a significant downregulation of a set of genes including CAV-1, CTGF, TIMP-3, MMP-1, ITGA-1, LOX, ITGA-2, PLG and CEBPB encoding various biological response modifiers and transcription factors. Our results suggest that chronic hepatitis C is associated with distinct patterns of gene expression modulation in pathways associated with the regulation of immune responses and development of fibrosis.
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Galbiati, Ferruccio, Daniela Volonte', Jun Liu, Franco Capozza, Philippe G. Frank, Liang Zhu, Richard G. Pestell, and Michael P. Lisanti. "Caveolin-1 Expression Negatively Regulates Cell Cycle Progression by Inducing G0/G1 Arrest via a p53/p21WAF1/Cip1-dependent Mechanism." Molecular Biology of the Cell 12, no. 8 (August 2001): 2229–44. http://dx.doi.org/10.1091/mbc.12.8.2229.
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Caveolin-1 is a principal component of caveolae membranes in vivo. Caveolin-1 mRNA and protein expression are lost or reduced during cell transformation by activated oncogenes. Interestingly, the human caveolin-1 gene is localized to a suspected tumor suppressor locus (7q31.1). However, it remains unknown whether caveolin-1 plays any role in regulating cell cycle progression. Here, we directly demonstrate that caveolin-1 expression arrests cells in the G0/G1 phase of the cell cycle. We show that serum starvation induces up-regulation of endogenous caveolin-1 and arrests cells in the G0/G1 phase of the cell cycle. Moreover, targeted down-regulation of caveolin-1 induces cells to exit the G0/G1 phase. Next, we constructed a green fluorescent protein-tagged caveolin-1 (Cav-1-GFP) to examine the effect of caveolin-1 expression on cell cycle regulation. We directly demonstrate that recombinant expression of Cav-1-GFP induces arrest in the G0/G1 phase of the cell cycle. To examine whether caveolin-1 expression is important for modulating cell cycle progression in vivo, we expressed wild-type caveolin-1 as a transgene in mice. Analysis of primary cultures of mouse embryonic fibroblasts from caveolin-1 transgenic mice reveals that caveolin-1 induces 1) cells to exit the S phase of the cell cycle with a concomitant increase in the G0/G1 population, 2) a reduction in cellular proliferation, and 3) a reduction in the DNA replication rate. Finally, we demonstrate that caveolin-1-mediated cell cycle arrest occurs through a p53/p21-dependent pathway. Taken together, our results provide the first evidence that caveolin-1 expression plays a critical role in the modulation of cell cycle progression in vivo.
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Extermann, Martine, Biwei Cao, Anders E. Berglund, Jing-Yi Chern, Hye Sook Chon, Mihaela C. Cristea, Christopher Cubitt, et al. "Ovarian cancer: Age, prognosis, and biologic underpinnings." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e17555-e17555. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e17555.
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e17555 Background: The prognosis of ovarian cancer worsens markedly with age. Yet few data are available to explain this phenomenon. Two hypotheses can be made. Changes in pharmacokinetics (PK) and treatment tolerance limit the dosing of chemotherapy, and/or changes in tumor and host-tumor biology limit treatment efficacy. Objective:To identify PK, body composition, and biologic changes with age that may impact prognosis. We reported PK findings in a previous abstract (Extermann et al., ASCO 2021) In this abstract we focus on the biologic findings. Methods: We conducted a prospective cohort study of women with stage III/IV high-grade serous ovarian cancers treated with neoadjuvant intravenous carboplatin (C) AUC 5 every 3 weeks and paclitaxel (P) dosed either weekly at 80 mg/m2 or every 3 weeks at 175 mg/m2. Body composition was assessed using baseline CT scans at the L3 level. Pre- and post-chemotherapy plasma samples were assayed by ELISA for CRP, IL-6, TNF alpha, TNF-receptor 1 and 2, d-dimers, vitamins B12 and D, methylmalonic acid, and cortisol levels. Tissue samples pre- and post-chemotherapy were analyzed for gene expression, gene methylation, and immunohistochemistry for inflammatory markers and senescence. Toxicity was assessed as first cycle nadir ANC and G4 hematologic (H) or grade 3-4 non-hematologic (NH) toxicity by CTCAE 4.0 criteria over a 3 cycles follow-up. The correlation between continuous measures was assessed by Spearman correlation coefficient, and the association with toxicity was evaluated by Wilcoxon rank sum test. The association with relapse-free survival (RFS) and overall survival (OS) was calculated by Log-rank and Cox regression analyzes. Results: Seventeen patients, ages 38 to 86 (median 61) were eligible, 14 underwent surgery. Treatment delivery was high with a median relative dose intensity of 100%. The mean percentage of senescent cells (CAV-1 +) was 49.5% in the stroma, vs 12.8% in the tumor (p < 0.001) prechemotherapy, and 15.7% in the stroma vs 21.4% in the tumor post-chemotherapy (pre-post stroma p < 0.01). The percentage of PD-L1 positive cells and CTLA-4 positive cells was very low: mean < 1% both pre-and post-chemotherapy. The results from gene expression and methylation showed an increase in the inflammatory pathways and a decrease in the apoptosis pathways over time. Vitamin D levels decreased with age. Prechemotherapy CD8 percentage in the stroma and post chemotherapy d-dimers were associated with RFS. Conclusions: Neoadjuvant treatment delivery was high in an academic setting. Our results provide insights in the underexplored area of biologic response to chemotherapy in patients with ovarian cancer. Although our results did not provide clear candidates to explain the worsening of prognosis with age, they offer clues to develop future research on this issue.
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Lupu, Cristina, Hua Zhu, Jonathan Wren, and Florea Lupu. "Novel Protein Encoded by C6orf105 Regulates Tissue Factor Pathway Inhibitor Expression and Function In Human Endothelial Cells In Normal Conditions and During Androgen Stimulation." Blood 116, no. 21 (November 19, 2010): 348. http://dx.doi.org/10.1182/blood.v116.21.348.348.
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Abstract Abstract 348 Cardiovascular disease (CVD) and thrombotic complications (deep vein thrombosis/venous thromboembolism, DVT/VTE) represent major health problems, with men having higher rates of clinical events than women. Tissue Factor Pathway Inhibitor (TFPI) is the key natural inhibitor of coagulation: it neutralizes factor Xa (FXa) and inhibits tissue factor-factor VIIa (TF-FVIIa) in the presence of FXa. In vivo most of TFPI is in endothelial cells (EC), reversibly bound to yet unidentified receptors, and glycosyl phosphatidylinositol-floated in caveolae and/or lipid raft microdomains. Intravascular thrombosis occurs frequently in older people, especially associated with cancer, diabetes, or CVD. TF is directly involved in tumor hypercoagulability, angiogenesis and metastasis. Cell-associated TFPI is the most physiologically significant inhibitor of the TF-FVIIa- triggered coagulation pathway; nevertheless, very few mechanisms/factors that could regulate the natural expression of TFPI have been identified so far. Here we describe androgen treatment of EC as a novel way to preserve and/or enhance a healthy vascular function, particularly related to the regulation of TFPI-dependent anticoagulant function of the endothelium. Our hypothesis is that a yet uncharacterized protein encoded by C6orf105 is a novel regulator of TFPI expression and function in EC, both in native conditions and during androgen stimulation. “In silico” data mining using global meta-analysis of publicly available NCBI's Gene Expression Omnibus 2-channel human microarray datasets identified C6orf105 as highly co-expressed with TFPI and following a parallel co-regulation. The uncharacterized protein has 230-aa, Mr ∼27 kDa, 5–6 predicted transmembrane domains and has sequence similarities with members of the androgen-inducible genes family. We tentatively named it TFPI-Regulating Factor (TFPI-RF). Real-time qPCR and western blot confirmed robust expression of TFPI-RF in EC in culture (HUVEC and EA.hy926 hybrid cell line). By immunofluorescence (IMF) TFPI-RF appears both on the cell surface and intracellularly co-localizing with TFPI and caveolin-1 (cav-1). Post-transcriptional (siRNA) down-regulation of TFPI-RF decreased TFPI, both as protein (∼2-times) and as anticoagulant activity (∼3-fold), apparently by reducing the co-localization of the TF-FVIIa-FXa-TFPI complex with cav-1. Over-expression of TFPI-RF in HUVEC and EA.hy926 led to enhanced co-localization of TFPI-RF with TFPI, and increased TFPI mRNA and anticoagulant activity (∼2-times). Western blot of cellular fractions after extraction with Triton X-114 and temperature-induced phase separation revealed the presence of TFPI and TFPI-RF in detergent-insoluble fractions, which suggests predominant lipid raft association. IMF illustrates TFPI-RF co-clustering with TFPI and cav-1 or GM1 (raft marker) in live EC incubated with anti-TFPI antibody or Cholera Toxin-B, respectively. The effect of androgens was studied by incubating EC with 30 nM dehydrotestosterone (DHT) or equivalent testosterone-BSA (cell-impermeable). 1-h incubation led to 2-times enhanced TFPI activity, increased co-localization of the quaternary complex with cav-1 and TFPI-RF, and enhanced exposure of TFPI and TFPI-RF on the cell surface. 24-h treatment with DHT up-regulates the expression of both TFPI (2-fold) and TFPI-RF (3-fold), as well as the TFPI inhibitory activity against FXa. DHT failed to enhance TFPI activity in TFPI-RF siRNA EC. Our results reveal a novel mechanism of up-regulation of the anticoagulant activity of endogenous TFPI in response to physiological levels of androgen. While the precise role of androgens in the ageing process is unclear, it is believed that androgen replacement could have beneficial influence on the declining functions in the elderly. Our data could expand on the effects of androgens on the haemostatic function of the endothelium and discover new roles for novel proteins like C6orf105/TFPI-RF in enhancing the endothelial anticoagulant function. These may open possibilities to manipulate the cellular endogenous TFPI and/or other intrinsic factors to counteract pro-thrombotic states associated with CVD, DVT/VTE, sepsis and cancer. Disclosures: No relevant conflicts of interest to declare.
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Kushner, Brian H., Kim Kramer, Shakeel Modak, Suresh C. Jhanwar, and Nai-Kong V. Cheung. "Secondary Leukemia (Sl)/Myelodysplasia (MDS) and Bone Marrow (BM) Chromosomal Aberrations after Dose-Intensive Chemotherapy for Neuroblastoma (NB)." Blood 104, no. 11 (November 16, 2004): 5090. http://dx.doi.org/10.1182/blood.v104.11.5090.5090.
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Abstract We previously described SL/MDS in 3/53 newly-diagnosed NB patients (pts) who received 4 cycles of high-dose cyclophosphamide (4200 mg/m2)-doxorubicin (75 mg/m2)-vincristine (CAV) and 3 cycles of high-dose cisplatin (200 mg/m2)-etoposide (600 mg/m2) (P/E), ± local radiotherapy (RT), ± immunotherapy using the anti-GD2 3F8 antibody, ± targeted RT using 131-I-3F8. With longer follow-up and the addition of a further 11 pts who received 7 cycles and 5 pts who received 6 cycles, there are 3 more cases of SL/MDS (Table1), which gives SL or MDS in 6/69 pts. Table 1. Pts with Secondary Leukemia or MDS Age From Dx Presentation Type Cytogenetics * all 3 received 7 cycles; 2 also received local RT and 3F8 ** all 3 received 7 cycles, local RT, 3F8, and 131-I-3F8 Previously reported cases (J Clin Oncol16:3880, 1998)* 4y 15m surveillance BM M2 del(9)(q13q34),del(11)(q23q25) 5y 27m thrombocytopenia MDS del(5)(q11), der(7)t(7;17)(q11,q11), −17 12y 7m monocytosis M5 del(11)(q23) (rearranged MLL gene) New cases** 3y 12m leukocytosis ALL t(4;11)(q21;q23) (rearranged MLL) 8y 50m thrombocytopenia MDS del(5q) and del(7q) 25y 24m thrombocytopenia MDS del(7q) This SL risk was a reason for subsequently limiting induction to 3 CAV and 2 P/E. At 4+-to-72+ months (median, 19+), SL/MDS has not occurred in 46 pts treated with 5 cycles, including 19 who received thiotepa-topotecan-carboplatin (TTC) with an autologous stem-cell transplant and 11 who received both TTC and oral etoposide (E) maintenance. In routine surveillance studies, 4 pts in the 6/7-cycle group had BM cytogenetic changes (worrisome for SL) that spontaneously resolved, and 1 pt in the 5-cycle group had a cytogenetic aberration that has persisted in >90% of BM cells for 15+ months, without morphologic or clinical evidence of SL/MDS (Table 2). Allo-transplant was recommended, but not done, for this patient and for the 10 yr old with a t(3;6) translocation that was documented in 20%-to-100% of BM mitoses for 26 months before finally disappearing (Table 2). Table 2. Pts with chromosomal aberrations but no SL or MDS Age From Dx # of Cycles, other Rx* Cytogenetics, Duration * all of these pts also received 3F8 18y 10m 7, local RT inv(11)(q21q23) (rearranged MLL), 1m 6y 21m 7, local RT, 131-I-3F8 t(2;16)(q31;q22) t(6;10)(q21;p13), 4m 10y 22m 6, local RT, 131-I-3F8 der(6) t(3,6)(q23, p25), 26m 6y 24m 7, local RT, 131-I-3F8 dup(1)(q21q32), 14m 5y 17m 5, local RT, TTC, oral E t(4;11)(p12;q23) (rearranged MLL), 15m+ In prior-treated NB pts, we also found transient BM cytogenetic abnormalities, some associated with leukemia or MDS, including del(16) (q22) and del(7q), though others are not, including inv(17) (p13q23). We conclude that fewer cycles of dose-intensive induction may reduce risks of SL/MDS and that BM cytogenetic abnormalities do not invariably evolve into SL or MDS. The nature of other genetic or epigenetic abnormalities that underlie such a transformation is currently unknown.
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Casas, Mariana, Reinaldo Figueroa, Gonzalo Jorquera, Matías Escobar, Jordi Molgó, and Enrique Jaimovich. "IP3-dependent, post-tetanic calcium transients induced by electrostimulation of adult skeletal muscle fibers." Journal of General Physiology 136, no. 4 (September 13, 2010): 455–67. http://dx.doi.org/10.1085/jgp.200910397.
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Tetanic electrical stimulation induces two separate calcium signals in rat skeletal myotubes, a fast one, dependent on Cav 1.1 or dihydropyridine receptors (DHPRs) and ryanodine receptors and related to contraction, and a slow signal, dependent on DHPR and inositol trisphosphate receptors (IP3Rs) and related to transcriptional events. We searched for slow calcium signals in adult muscle fibers using isolated adult flexor digitorum brevis fibers from 5–7-wk-old mice, loaded with fluo-3. When stimulated with trains of 0.3-ms pulses at various frequencies, cells responded with a fast calcium signal associated with muscle contraction, followed by a slower signal similar to one previously described in cultured myotubes. Nifedipine inhibited the slow signal more effectively than the fast one, suggesting a role for DHPR in its onset. The IP3R inhibitors Xestospongin B or C (5 µM) also inhibited it. The amplitude of post-tetanic calcium transients depends on both tetanus frequency and duration, having a maximum at 10–20 Hz. At this stimulation frequency, an increase of the slow isoform of troponin I mRNA was detected, while the fast isoform of this gene was inhibited. All three IP3R isoforms were present in adult muscle. IP3R-1 was differentially expressed in different types of muscle fibers, being higher in a subset of fast-type fibers. Interestingly, isolated fibers from the slow soleus muscle did not reveal the slow calcium signal induced by electrical stimulus. These results support the idea that IP3R-dependent slow calcium signals may be characteristic of distinct types of muscle fibers and may participate in the activation of specific transcriptional programs of slow and fast phenotype.
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Cloquell, Ana, Isidro Mateo, Stefano Gambera, Martí Pumarola, Ramon Alemany, Javier García-Castro, and Ana Judith Perisé-Barrios. "Systemic cellular viroimmunotherapy for canine high-grade gliomas." Journal for ImmunoTherapy of Cancer 10, no. 12 (December 2022): e005669. http://dx.doi.org/10.1136/jitc-2022-005669.
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BackgroundOncolytic viruses constitute a growing field of interest, both in human and veterinary oncology, given that they are particularly helpful for treating non-surgical tumors and disseminated cancer, such as high-grade gliomas. Companion dogs present malignant gliomas with biological, genetic, phenotypic, immunological, and clinical similarities to human gliomas. These features favor comparative approaches, leading to the treatment of canine oncological patients to achieve translational applications to the human clinic. The systemic administration of oncolytic viruses presents a challenge due to their limitations in effectively targeting tumors and metastases. Therefore, the aim of this study is to evaluate the safety and antitumor activity of a virotherapy used in spontaneous canine tumors.MethodsTen dogs with high-grade rostrotentorial gliomas underwent weekly systemic endovenous cellular virotherapy with dCelyvir (canine mesenchymal stem cells infected with the canine oncolytic adenovirus ICOCAV17) for 8 weeks. Efficacy was determined in seven dogs according to the Response Assessment in Veterinary Neuro-Oncology criteria considering clinical status and MRI measurements. Medical history, physical and neurological examinations, and vaccination status were evaluated prior to and during follow-up. Safety was evaluated by physical examinations and hematological and biochemical changes in peripheral blood. Immune populations were analyzed by flow cytometry in peripheral blood and by gene expression and immunohistochemistry in the tumor microenvironment.ResultsThe treatment was well tolerated and major adverse effects were not observed. Two dogs had partial responses (76% and 86% reduction in tumor size), and 3/7 showed stable disease. ICOCAV17 was detected in peripheral blood in nine dogs, and a correlation between the ICOCAV17 particles and anti-canine adenovirus (CAV) antibodies was observed. ICOCAV17 was detected in 3/9 tumor tissues after necropsies. Regarding tumor-infiltrating lymphocytes, the dogs with disease stabilization and partial response tended to have reduced memory B-cell infiltration and increased monocyte/macrophage lineage cells.ConclusionsThese findings indicate that dCelyvir is safe and presents efficacy in canine rostrotentorial high-grade gliomas. These data are relevant to the ongoing phase Ib regulated human clinical trial that is administering this virotherapy to children, adolescents, and young adults with diffuse pontine glioma. Celyvir should be further explored as a treatment in veterinary and human neuro-oncology.
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Whitelaw, E., A. Coates, and N. J. Proudfoot. "Globin gene transcripts can utilize histone gene 3′ end processing signals." Nucleic Acids Research 14, no. 17 (1986): 7059–70. http://dx.doi.org/10.1093/nar/14.17.7059.
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Evans, Mark J., and Richard C. Scarpulla. "Introns in the 3'-untranslated region can inhibit chimeric CAT and β-galactosidase gene expression." Gene 84, no. 1 (December 1989): 135–42. http://dx.doi.org/10.1016/0378-1119(89)90147-9.
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Wilson, Sarah M., Brian S. Schmutzler, Joel M. Brittain, Erik T. Dustrude, Matthew S. Ripsch, Jessica J. Pellman, Tae-Sung Yeum, et al. "Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides." Journal of Biological Chemistry 287, no. 42 (August 13, 2012): 35065–77. http://dx.doi.org/10.1074/jbc.m112.378695.
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N-type Ca2+ channels (CaV2.2) are a nidus for neurotransmitter release and nociceptive transmission. However, the use of CaV2.2 blockers in pain therapeutics is limited by side effects resulting from inhibition of the physiological functions of CaV2.2 within the CNS. We identified an anti-nociceptive peptide (Brittain, J. M., Duarte, D. B., Wilson, S. M., Zhu, W., Ballard, C., Johnson, P. L., Liu, N., Xiong, W., Ripsch, M. S., Wang, Y., Fehrenbacher, J. C., Fitz, S. D., Khanna, M., Park, C. K., Schmutzler, B. S., Cheon, B. M., Due, M. R., Brustovetsky, T., Ashpole, N. M., Hudmon, A., Meroueh, S. O., Hingtgen, C. M., Brustovetsky, N., Ji, R. R., Hurley, J. H., Jin, X., Shekhar, A., Xu, X. M., Oxford, G. S., Vasko, M. R., White, F. A., and Khanna, R. (2011) Suppression of inflammatory and neuropathic pain by uncoupling CRMP2 from the presynaptic Ca2+ channel complex. Nat. Med. 17, 822–829) derived from the axonal collapsin response mediator protein 2 (CRMP2), a protein known to bind and enhance CaV2.2 activity. Using a peptide tiling array, we identified novel peptides within the first intracellular loop (CaV2.2(388–402), “L1”) and the distal C terminus (CaV1.2(2014–2028) “Ct-dis”) that bound CRMP2. Microscale thermophoresis demonstrated micromolar and nanomolar binding affinities between recombinant CRMP2 and synthetic L1 and Ct-dis peptides, respectively. Co-immunoprecipitation experiments showed that CRMP2 association with CaV2.2 was inhibited by L1 and Ct-dis peptides. L1 and Ct-dis, rendered cell-penetrant by fusion with the protein transduction domain of the human immunodeficiency virus TAT protein, were tested in in vitro and in vivo experiments. Depolarization-induced calcium influx in dorsal root ganglion (DRG) neurons was inhibited by both peptides. Ct-dis, but not L1, peptide inhibited depolarization-stimulated release of the neuropeptide transmitter calcitonin gene-related peptide in mouse DRG neurons. Similar results were obtained in DRGs from mice with a heterozygous mutation of Nf1 linked to neurofibromatosis type 1. Ct-dis peptide, administered intraperitoneally, exhibited antinociception in a zalcitabine (2′-3′-dideoxycytidine) model of AIDS therapy-induced and tibial nerve injury-related peripheral neuropathy. This study suggests that CaV peptides, by perturbing interactions with the neuromodulator CRMP2, contribute to suppression of neuronal hypersensitivity and nociception.
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Debsharma, Sanjoy K., Md Abu Syed, Md Hannan Ali, Sheikh Maniruzzaman, Popy R. Roy, Marian Brestic, Ahmed Gaber, and Akbar Hossain. "Harnessing on Genetic Variability and Diversity of Rice (Oryza sativa L.) Genotypes Based on Quantitative and Qualitative Traits for Desirable Crossing Materials." Genes 14, no. 1 (December 21, 2022): 10. http://dx.doi.org/10.3390/genes14010010.
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Yield is a complex parameter of rice due to its polygonal nature, sometimes making it difficult to coat the selection process in the breeding program. In the current study, 34 elite rice genotypes were assessed to evaluate 3 locations for the selection of desirable rice cultivars suitable for multiple environments based on genetic diversity. In variance analysis, all genotypes have revealed significant variations (p ≤ 0.001) for all studied characters, signifying a broader sense of genetic variability for selection purposes. The higher phenotypic coefficient of variation (PCV) and genotypic coefficient of variation (GCV) were found for yield-associated characteristics such as the number of grains panicle−1 (GP), panicles hill−1 (PPH), and tillers hill−1 (TILL). All of the characters had higher heritability (greater than 60%) and higher genetic advance (greater than 20%), which pointed out non-additive gene action and suggested that selection would be effective. The most significant traits causing the genotype variants were identified via principal component analysis. In the findings of the cluster analysis, 34 elite lines were separated into 3 categories of clusters, with cluster II being chosen as the best one. The relationship matrix between each elite cultivar and traits was also determined utilizing a heatmap. Based on multi-trait genotype-ideotype distance index (MGIDI), genotypes Gen2, Gen4, Gen14, Gen22, and Gen30 in Satkhira; Gen2, Gen6, Gen7, Gen15, and Gen30 in Kushtia; and Gen10, Gen12, Gen26, Gen30, and Gen34 in Barishal were found to be the most promising genotypes. Upon validation, these genotypes can be suggested for commercial release or used as potential breeding material in crossing programs for the development of cultivars suitable for multiple environments under the future changing climate.
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de la Taille, Alexandre, Jacques Irani, Theo M. de Reijke, and Alexander Haese. "CAN PROSTATE CANCER GENE 3 (PCA3) PREDICT INITIAL BIOPSY OUTCOME?" Journal of Urology 181, no. 4 (April 2009): 655. http://dx.doi.org/10.1016/s0022-5347(09)61838-3.
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Perera, Imara Y., and Raymond E. Zielinski. "Structure and expression of the Arabidopsis CaM-3 calmodulin gene." Plant Molecular Biology 19, no. 4 (July 1992): 649–64. http://dx.doi.org/10.1007/bf00026791.
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Jiang, Jie, Daryl Cole, Nigel Westwood, Lee Macpherson, Farzin Farzaneh, Ghulam J. Mufti, Mahvash Tavassoli, and Joop Gaken. "Apoptin Induced Tumour Specific Killing Via Protein Kinase C Isoforms: A Potential Therapeutic Strategy In Plasma Cell Dyscrasias." Blood 116, no. 21 (November 19, 2010): 5039. http://dx.doi.org/10.1182/blood.v116.21.5039.5039.
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Abstract Abstract 5039 There is mounting evidence that malignant cells have an intrinsic ability to prevent apoptosis. In the present study we provide evidence that the ectopic expression of Apoptin can restore the failing apoptosis program in myeloma cells via protein kinase C b (PKCb) and overcome intrinsic or acquired resistance to cell death. Apoptin (VP3), a chicken anemia virus (CAV)-derived protein has been shown to possess tumor specific cytotoxicity; its expression induces apoptosis in human tumor and transformed cells but there is little or no cytotoxic effect in normal human cells or cell lines derived from different tissues including peripheral blood mononuclear cells, fibroblast and epithelial cells. Several studies have shown that the tumor specific killing of Apoptin correlates with its phosphorylation and its subcellular localization. In cancer cells, Apoptin is localized in the nucleus and is phosphorylated on threonine108 by an as yet unknown kinase, whereas in normal cells Apoptin is detected in the cytoplasm and is essentially unphosphorylated. We developed a lentiviral vector encoding a GFP-Apoptin fusion gene (LV-GFP-AP), which delivers the Apoptin gene efficiently to haematopoietic cells. Apoptin significantly and selectively killed a number of leukemia cell lines including K562, HL60, U937, KG1 and NB4. In particular, the dexamethasone resistant multiple myeloma cell line MM1.R and the dexamethasone sensitive cell line MM1.S were efficiently killed by Apoptin. In contrast normal CD34+ cells were not killed and maintained their differentiation potential in multilineage colony formation assays. In addition, we showed that the dexamethasone resistant MM1.R cells were considerably more susceptible to Apoptin induced cell death than the parental matched MM1.S cells. This correlated with increased phosphorylation and activation of the Apoptin protein in MM1.R cells. Expression profiling of MM1.R and MM1.S cells identified a number of differentially expressed kinases. PKCb was over-expressed 9 fold in MM1.R cells and we showed, by immunoprecipitation and in vivo kinase studies, that this kinase was responsible for Apoptin phosphorylation. Analysis of the Apoptin amino acid sequence for potential phosphorylation sites indicated seven putative phosphorylation sites corresponding to the PKC kinase consensus motifs (S/TXK/R or S/TXXK/R). These sites included Thr-108, which has been previously shown to be phosphorylated in tumor cells, but not in normal cells. In vitro studies showed that recombinant Apoptin protein was phosphorylated by recombinant GST-PKCb protein at the Thr-108 site. Addition of a PKCb specific inhibitor resulted in diminished Apoptin phosphorylation whilst an unrelated inhibitor had no such effect. Furthermore, shRNA knockdown or drug mediated inhibition of PKCb in vivo significantly reduced Apoptin phosphorylation. Finally, we found that Apoptin mediated cell death proceeded via the up-regulation of PKCb, activation of caspase-9/3, cleavage of the PKCd catalytic domain and down-regulation of MERTK and AKT protein kinases. Collectively these results demonstrate a novel pathway for Apoptin activation involving PKCb and PKCd. Our results show that Apoptin is able to effectively eliminate multiple myeloma cells which have become resistant to dexamethasone. In addition, this study has led to the identification of tumor specific cellular targets such as PKCb, whose modulation by shRNAs and small molecule drugs can induce strong anti-myeloma effects. Importantly, the evidence from our data suggests that protein kinase C inhibitors may have an important therapeutic role in plasma cell neoplasia. Disclosures: No relevant conflicts of interest to declare.
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Ran, Fourier, Arafa, Liesecke, Sjöstrand, Waldenlind, Steinberg, and Belin. "Anoctamin 3: A Possible Link between Cluster Headache and Ca2+ Signaling." Brain Sciences 9, no. 8 (July 30, 2019): 184. http://dx.doi.org/10.3390/brainsci9080184.
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Cluster headache is a severe primary headache characterized by extremely painful attacks of unilateral headache. Verapamil is commonly used as a prophylactic treatment with good effect. In order to search for new pathways involved in the pathophysiology of cluster headache, we analyzed genetic variants that were previously linked to verapamil response in migraine in a Swedish cluster headache case-control sample. We used TaqMan qPCR for genetic screening and performed a gene expression analysis on associated genes in patient-derived fibroblasts, and further investigated which reference genes were suitable for analysis in fibroblasts from cluster headache patients. We discovered a significant association between anoctamin 3, a gene encoding a calcium-activated ion channel, and cluster headache. The association was not dependent on verapamil treatment since the associated variant, rs1531394, was also overrepresented in patients not using verapamil. No difference was found in the anoctamin 3 gene expression between controls and patients. Also, we determined that TBP, IPO8 and PDHB were suitable reference genes in cluster headache fibroblasts. This finding is the first report of an association between a variant in a gene encoding an ion-channel and cluster headache, and the first significant genetic evidence of calcium involvement in cluster headache pathophysiology.
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Dode, Leonard, Christine De Greef, Irina Mountian, Marlene Attard, Margaret M. Town, Rik Casteels, and Frank Wuytack. "Structure of the Human Sarco/Endoplasmic Reticulum Ca2+-ATPase 3 Gene." Journal of Biological Chemistry 273, no. 22 (May 29, 1998): 13982–94. http://dx.doi.org/10.1074/jbc.273.22.13982.
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Hu, Jiabao, Youyi Zhang, Man Zhang, Kimran Jean Jacques, Yaya Li, Jiachu Sun, Yang Yang, Shanliang Xu, Yajun Wang, and Xiaojun Yan. "Jellyfish venom can induce apoptosis in fish by P53-inducible gene 3." Aquaculture 547 (January 2022): 737518. http://dx.doi.org/10.1016/j.aquaculture.2021.737518.
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Chehboun, Salma, Jérémie Labrecque-Carbonneau, Sarah Pasquin, Yasmine Meliani, Bouchra Meddah, Walter Ferlin, Mukut Sharma, Aurélie Tormo, Jean-François Masson, and Jean-François Gauchat. "Epstein-Barr virus-induced gene 3 (EBI3) can mediate IL-6trans-signaling." Journal of Biological Chemistry 292, no. 16 (March 9, 2017): 6644–56. http://dx.doi.org/10.1074/jbc.m116.762021.
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Jones, Rachel, Meredith B. Baker, Martina Weber, David G. Harrison, Gang Bao, and Charles D. Searles. "Molecular beacons can assess changes in expression and 3′-polyadenylation of human eNOS mRNA." American Journal of Physiology-Cell Physiology 296, no. 3 (March 2009): C498—C504. http://dx.doi.org/10.1152/ajpcell.00462.2008.
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The endothelium plays an essential role in maintaining vascular homeostasis, and it fulfills this role by modulating intracellular signaling and gene expression in response to chemical and mechanical stimuli. Assessing changes in endothelial gene expression is essential to understanding how physiological and pathophysiological processes modulate vascular homeostasis. Here we describe the use of molecular beacons to rapidly and quantitatively assess expression and 3′-polyadenylation of a gene that is important for vascular homeostasis, endothelial nitric oxide synthase (eNOS). Single- and dual-fluorescence resonance energy transfer (FRET) molecular beacon hybridization assays were developed to measure changes in mRNA levels and 3′-polyadenylation, respectively, in primary human endothelial cell cultures subjected to laminar shear stress or statin treatment. Optimized beacon hybridization assays took ∼15 min to perform, and eNOS mRNA levels were validated by quantitative real-time RT-PCR. Competitive inhibition assays and posttranscriptional silencing of eNOS expression were used to verify the specificity of molecular beacon fluorescence. Finally, the dual-FRET method was used to assess eNOS polyadenylation in tissues isolated from mice subjected to exercise training. These data demonstrate that molecular beacons can be used to rapidly and efficiently measure endothelial gene expression and 3′-polyadenylation. This approach could easily be adapted for studies of other endothelial genes and has promise for applications in live endothelial cells.
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Barnes, Kyra J., and Nick J. Spencer. "Can colonic migrating motor complexes occur in mice lacking the endothelin-3 gene?" Clinical and Experimental Pharmacology and Physiology 42, no. 5 (April 23, 2015): 485–95. http://dx.doi.org/10.1111/1440-1681.12380.
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DAVIDSON, JEFFREY N., GADIPARTHI N. RAO, LEE NISWANDER, CARLA ANDREANO, CELESTE TAMER, and KUEY-CHU CHEN. "Organization and Nucleotide Sequence of the 3′ End of the Human CAD Gene." DNA and Cell Biology 9, no. 9 (November 1990): 667–76. http://dx.doi.org/10.1089/dna.1990.9.667.
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Gabellini, Nadia, Stefania Bortoluzzi, Gian A. Danieli, and Ernesto Carafoli. "The human SLC8A3 gene and the tissue-specific Na+/Ca2+ exchanger 3 isoforms." Gene 298, no. 1 (September 2002): 1–7. http://dx.doi.org/10.1016/s0378-1119(02)00982-4.
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Zhou, G. L., Y. Cao, Y. Z. Xin, Y. F. Song, and H. G. Jin. "Alternative polyadenylation and polymorphisms of 3'untranslated regions of bovine BBOX1 gene." Czech Journal of Animal Science 63, No. 5 (April 26, 2018): 188–94. http://dx.doi.org/10.17221/105/2016-cjas.
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l-Carnitine, a key element in fatty acid metabolism and energy production, is biosynthesized from gamma-butyro-betaine by the catalysis of gamma-butyrobetaine hydroxylase (BBOX1). We cloned three different 3'untranslated regions (3'UTRs) alternative polyadenylation (APA) transcripts of the BBOX1 gene with different 3'UTR length (GenBank Accession Nos. KX431577, KX431578, KX431579). Two polymorphisms, NM_001101881.2: g.1797_1798insTGC and g.1935T>C, were revealed in 3'UTR of BBOX1 gene. They created or disrupted a restriction site for endonuclease BbvI and HincII, respectively. Moreover, the single nucleotide polymorphism (SNP) g.1935T>C can create or disrupt polyadenylation signals PAS3 resulting in the presence of APA3 transcript variant. Marker-trait association analyses showed that the BBOX1-BbvI and BBOX1-HincII loci were significantly associated with muscle fibre diameter, shear force, net meat weight, and carcass weight (P < 0.01). Moreover, we also found a significant association of combined genotypes with cooking loss, muscle fibre diameter, shear force, net meat weight, and carcass weight (P < 0.01). The results of this study provide the evidence that polymorphisms in BBOX1 gene are associated with meat quality and carcass traits in Chinese Red cattle, and may be used as a candidate for marker assisted selection in beef cattle breeding program.
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Vito, P., E. Lacan , and L. D'Adamio. "Interfering with Apoptosis: Ca2+-Binding Protein ALG-2 and Alzheimer's Disease Gene ALG-3." Science 271, no. 5248 (January 26, 1996): 521–25. http://dx.doi.org/10.1126/science.271.5248.521.
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Varchenko, O., M. Kuchuk, M. Parii, and Y. Symonenko. "Matching of the GFP Gene Expression Levels by Different Terminator Sequences Regulation." Mikrobiolohichnyi Zhurnal 82, no. 6 (November 30, 2020): 74–83. http://dx.doi.org/10.15407/microbiolj82.06.074.
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The ability to express foreign genes in plant cells provides a powerful tool for studying the function of specific genes. In addition, the creation of genetically modified plants may provide new important features that are useful for industrial production or pharmaceutical applications. One of the key parameters for the development of a high level of heterologous genes expression is the efficiency of terminators used in genetic engineering, since the level of gene expression depends on its choice. Aim. Study of the gfp gene expression regulation in Nicotiana rustica L. tissues by different terminators. Methods. The Golden Gate method of molecular cloning was used for genetic constructs creation. The tissues of N. rustica plants were infiltrated by the created genetic vectors for transient gene expression. The expression level was determined by spectrofluorometric (level of green fluorescent protein (GFP) fluorescence) and protein analysis: determination of water-soluble proteins concentration and its electrophoresis separation in polyacrylamide gel (PAGE). Results. Five different terminators with polyadenylation signal/3’-untranslated region (3’UTR) were selected for the study: the 7th gene isolated from Agrobacterium tumefaciens L. (Atug7), the terminator of the gene that encode mannopinsyntase from A. tumefaciens (mas), the terminator of tomato (Solanum lycopersum L.) adenosine 5’-triphosphatase (ATPase), the potato histone H4 terminator (Solanum tuberosum L.) and the 35S Cauliflower Mosaic Virus (35S CaMV) terminator. All transcriptional units additionally contained a 5’-untranslated region out of the 2B gene from the family of genes encoding the small subunit of Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) (5’UTR RbcS2B), the coding sequence of the gfp gene and double 35S Cauliflower Mosaic Virus promoter (D35S CaMV). Thus, we created 5 genetic constructs with different terminator sequences. The presence of recombinant GFP protein in total protein extracts and its identity to standard protein was proved by the spectrofluorometric and PAGE analyzes. For the first time was shown the difference of GFP reporter protein accumulation in N. rustica tissues by terminator regulation of transient gfp gene expression. Conclusions. We detected the highest expression of the gfp gene when the Atug7 terminator was used and the lowest level with the histone H4 terminator. The difference between protein accumulations using these terminators was in 2.89 times. It showed that the terminator sequence has a high influence on the gene expression. It choice is an important step in genetic constructs creation, since terminator can be used for regulating the level of gene expression depending on the goals.