DOCSLIB.ORG

Intra-Erythrocyte Cation Concentrations in Relation to the C1797T B-Adducin Polymorphism in a General Population

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Intra-Erythrocyte Cation Concentrations in Relation to the C1797T B-Adducin Polymorphism in a General Population Journal of Human Hypertension (2007) 21, 387–392 & 2007 Nature Publishing Group All rights reserved 0950-9240/07 $30.00 www.nature.com/jhh ORIGINAL ARTICLE Intra-erythrocyte cation concentrations in relation to the C1797T b-adducin polymorphism in a general population T Richart1, L Thijs1, T Kuznetsova1, V Tikhonoff1,2, L Zagato3, P Lijnen1, R Fagard1, J Wang4, G Bianchi3 and JA Staessen1 1Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, Studies Coordinating Centre, University of Leuven, Leuven, Belgium; 2Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy; 3Division of Nephrology, Dialysis and Hypertension, University Vita Salute San Raffaele, Milan, Italy and 4Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai, China Genetic variability in the ADD1 (Gly460Trp) and ADD2 P ¼ 0.93). In men, iK, iMg and iNa did not differ according (C1797T) subunits of the cytoskeleton protein adducin to ADD1 genotypes. In men, iK (R 2 ¼ 0.128) increased plays a role in the pathogenesis of hypertension, with age and serum Na þ , but decreased with serum total possibly via changes in intracellular cation concentra- calcium and the daily intake of alcohol. iMg (R2 ¼ 0.087) tions. ADD2 1797CC homozygous men have decreased decreased with age, but increased with serum total erythrocyte count and hematocrit. We investigated calcium. After adjustment for these covariates (Pp0.04 possible association between intra-erythrocyte cations for all), findings in men for iK (CC versus T: 85.8 versus and the adducin polymorphisms. In 259 subjects (mean 87.3 mmol/l; P ¼ 0.14) and iMg (1.91 versus 1.82 mmol/l; age 47.7 years), we measured intra-erythrocyte Na þ P ¼ 0.03) remained consistent. In 136 women, none of [iNa], K þ [iK] and Mg2 þ [iMg], serum cations and the phenotype–genotype relations reached significance. adducin genotypes. Genotype frequencies (ADD1: GlyGly Changes in intra-erythrocyte cations in ADD2 1797CC 61.5%, Trp 38.5%; ADD2: CC 80.4%, T 19.6%) complied homozygous men might lead to osmotic fragility of with Hardy–Weinberg proportions. In men, ADD2 CC erythrocytes, but to what extent they reflect systemic homozygotes (n ¼ 100) compared to T-carriers (n ¼ 23) changes or are possibly involved in blood pressure had slightly lower iK (85.8 versus 87.5 mmol/l cells; P ¼ regulation remains unknown. 0.107), higher iMg (1.92 versus 1.80 mmol/l cells; P ¼ Journal of Human Hypertension (2007) 21, 387–392. 0.012), but similar iNa (6.86 versus 6.88 mmol/l cells; doi:10.1038/sj.jhh.1002154; published online 15 February 2007 Keywords: adducin; erythrocytes; polymorphism; genetics; osmotic Introduction knockout mice show a phenotype characterised by mild anemia and compensated hemolysis.1,2 In The membrane-skeleton protein adducin stimulates humans, a common polymorphism (C1797T) occurs the assembly of the spectrin–actin network, which in exon 15 of the b-adducin gene. We have demon- determines the structural integrity of the cell strated previously in cross-sectional and prospec- membrane. Adducin is composed of either a- and tive studies that genetic variability in the subunits of b-ora- and g-subunits, which are encoded by the cytoskeleton protein adducin plays a role in the different genes. In erythrocytes, a- and b-adducin are pathogenesis of hypertension, possibly via altera- abundantly present, whereas most other tissues tion of the intracellular cation concentrations.3,4 predominantly express a-g-heterodimers. b-Adducin In addition, we have recently noticed that in men consuming alcohol, b-adducin CC homozygosity was associated with lower erythrocyte count, 5 Correspondence: Dr JA Staessen, Studies Coordinating Centre, haemoglobin level and haematocrit. The osmotic Laboratory of Hypertension, Hypertension and Cardiovascular stability of erythrocytes decreases with lower intra- Rehabilitation Unit, Department of Cardiovascular Diseases, cellular potassium concentration.6 We therefore Campus Gasthuisberg, Herestraat 49, box 702, Leuven, B-3000 measured the intra-erythrocyte concentration of Belgium. cations in a sub-sample of our previous study E-mail: [email protected] 5 Received 21 August 2006; revised 27 November 2006; accepted 10 population to test possible association with the December 2006; published online 15 February 2007 a- and b-adducin polymorphisms. Intra-erythrocyte cations and adducin T Richart et al 388 Methods iNa þ and 2.1270.12% for iK þ . The inter-assay variation determined in five blood samples was Study population 2.3771.03% for iNa þ and 3.2271.18% for iK þ . The Ethics Committee of the University of Leuven approved the protocol of the Flemish study on Environment, Genes and Health Outcomes Determination of genotypes (FLEMENGHO). All subjects gave informed consent. Genomic DNA was extracted from peripheral blood. From August 1985 to November 1990, we recruited a Allelic discrimination of the ADD1 460 glycine random sample of the households living in a (Gly)/460 tryptophan (Trp) and the ADD2 C1797 T geographically defined area of Northern Belgium.7 polymorphism was carried out using the 50-nuclease We stratified the sample by sex and age (20–39, assay9 on an ABI Prism 7700 apparatus (Perkin 40–59 and X60 years) to recruit equal numbers of Elmer, Foster City, CA, USA). The forward and participants in each of the six strata. From June 1996 reverse primers and the 460Gly and 460Trp probes to December 2000, we enrolled nuclear families, employed in the TAQMan2 assay were 50-CGTCCAC using the former participants (1985–1990) as index ACCTTAGTCTTCGACTT-30 50-GGAGAAGACAAGA persons. The participation rate among the 2310 TGGCTGAACTC-30,50-FAM-TTCCATTCTGCCCTTC subjects contacted was 66.1%. Our previous study5 CTCGGATAMRA-30 and 50-TET-TTCCATTCTGCCA included 1870 subjects with haematological pheno- TTCCTCGGAA-TAMRA-3,0 respectively (where FAM, types and the C1797T b-adducin genotype. Of these, TAMRA and TET are dyes used with the TAQMan 277 subjects were randomly selected and underwent system). For the ADD2 C1797T polymorphism, the additional measurements of their intra-erythrocyte forward and reverse primers and the 1797C and 1797T cation concentrations and the concentration of probes employed in the TAQMan2 assay were 50-AGG serum ionised calcium. We excluded 18 subjects, AACGAGAGCCAGGCTCT-30 50-TTCATCAAAACAC because of missing values. ACACCTACCAAT-30,50-VIC2-TTCTTCAGCGTTGC Trained nurses measured each participant’s blood CCTCCACATTAMRA2-30 and 50-FAM2-TCTTCAGT pressure (BP) five times consecutively by conven- GTTGCCCTCCACATCTG-TAMRA2-30 (where VIC2, tional sphygmomanometry after the subjects had TAMRA2 and FAM2 are dyes used with the rested for at least 5 min in the sitting position. These TAQMan system). Per 25 ml, the polymerase chain five readings were averaged for analysis. Hyper- reaction (PCR) fluid contained 50 ng of DNA, tension was defined as a BP of at least 140 mm Hg 200 nmol of primers, 50 nmol of FAM probe and systolic or 90 mm Hg diastolic, or as use of anti- 100 nmol of VIC probe. The amplification condi- hypertensive drugs. Body mass index (BMI) was tions were 501C for 2 min and 951C for 10 min, body weight in kilograms divided by height in followed by 40 cycles at 951C for 15 s and 621C for metres squared. We used a standardized and 1 min. The genotyping procedure was established validated8 questionnaire to collect information after we had confirmed the polymorphism (C1797T, on medical history, smoking habits, intake of starting from ATG; dbSNP number rs4984; URL: alcohol, use of medications and the menstrual cycle http://www.ncbi.nlm.nih.gov/SNP) by sequencing of women. From the type and number of alcoholic 17 individuals using the ABI Prism Big Dye beverages used each day, we calculated alcohol Terminator cycle sequencing ready reaction kit consumption in grams per day. (Applied Biosystems, Foster City, CA, USA). We tested the frequency of the polymorphism in a random population of 250 blood donors from North Italy, and found that the minor allele had a Measurement of phenotypes frequency of 15%. For quality control, 10% of the Venous blood samples were collected into ethylene- DNA samples in our study were genotyped in diamine-tetraacetic acid-containing tubes. Erythro- duplicate in a blinded fashion. Duplicate genotypes cyte count, haemoglobin, and haematocrit were were confirmatory in all samples. measured in whole-blood specimens with a SYS- MEX HST 403XE model automated cell counter (Systmex Corporation, Chuku, Kobe, Japan). Serum Statistical analysis ionised calcium and pH were determined using For database management and statistical analysis, an ICA2 ionised calcium analyser (Radiometer, we used SAS software, version 9.1.3 and JMP, Copenhagen, Denmark). version 6 (SAS Institute, Cary, NC, USA). Measure- Erythrocytes (1.5 ml) were washed three times ments with a skewed distribution were norma- with ice-cold 140 mM choline chloride. After centri- lised by logarithmic transformation. Comparisons fugation at 5500 r.p.m. at 41C for 3 min, the super- of means and proportions were performed using natant and the top layer of the cells were discarded Student’s t-test and Fisher’s exact test, respectively. by aspiration. The cells were lysed with double- We computed Pearson’s correlation coefficients distilled water and the Na þ ,Kþ and Mg2 þ concen- between the cation concentrations in erythrocytes trations were measured by atomic absorption and serum and compared
Load more

Recommended publications
  • Altered DNA Methylation in Children Born to Mothers with Rheumatoid
    Rheumatoid arthritis Ann Rheum Dis: first published as 10.1136/annrheumdis-2018-214930 on 29 May 2019. Downloaded from EPIDEMIOLOGICAL SCIENCE Altered DNA methylation in children born to mothers with rheumatoid arthritis during pregnancy Hilal Ince-Askan, 1 Pooja R Mandaviya,2 Janine F Felix,3,4,5 Liesbeth Duijts,3,6,7 Joyce B van Meurs,2 Johanna M W Hazes,1 Radboud J E M Dolhain1 Handling editor Josef S ABSTRACT Key messages Smolen Objectives The main objective of this study was to determine whether the DNA methylation profile of ► Additional material is What is already known about this subject? published online only. To children born to mothers with rheumatoid arthritis (RA) is ► Adverse exposures in early life are associated view please visit the journal different from that of children born to mothers from the with later-life health. online (http:// dx. doi. org/ 10. general population. In addition, we aimed to determine Epigenetic changes are thought to be one of the 1136annrheumdis- 2018- whether any differences in methylation are associated ► 214930). underlying mechanisms. with maternal RA disease activity or medication use There is not much known about the during pregnancy. ► For numbered affiliations see consequences of maternal rheumatoid arthritis end of article. Methods For this study, genome-wide DNA (RA) on the offsprings’ long-term health. methylation was measured at cytosine-phosphate- Correspondence to guanine (CpG) sites, using the Infinium Illumina What does this study add? Hilal Ince-Askan, Rheumatology, HumanMethylation 450K BeadChip, in 80 blood samples Erasmus Medical Centre, ► DNA methylation is different in children born to from children (mean age=6.8 years) born to mothers Rotterdam 3000 CA, The mothers with RA compared with mothers from Netherlands; with RA.
    [Show full text]
  • Analysis of the Indacaterol-Regulated Transcriptome in Human Airway
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/04/13/jpet.118.249292.DC1 1521-0103/366/1/220–236$35.00 https://doi.org/10.1124/jpet.118.249292 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:220–236, July 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Analysis of the Indacaterol-Regulated Transcriptome in Human Airway Epithelial Cells Implicates Gene Expression Changes in the s Adverse and Therapeutic Effects of b2-Adrenoceptor Agonists Dong Yan, Omar Hamed, Taruna Joshi,1 Mahmoud M. Mostafa, Kyla C. Jamieson, Radhika Joshi, Robert Newton, and Mark A. Giembycz Departments of Physiology and Pharmacology (D.Y., O.H., T.J., K.C.J., R.J., M.A.G.) and Cell Biology and Anatomy (M.M.M., R.N.), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Received March 22, 2018; accepted April 11, 2018 Downloaded from ABSTRACT The contribution of gene expression changes to the adverse and activity, and positive regulation of neutrophil chemotaxis. The therapeutic effects of b2-adrenoceptor agonists in asthma was general enriched GO term extracellular space was also associ- investigated using human airway epithelial cells as a therapeu- ated with indacaterol-induced genes, and many of those, in- tically relevant target. Operational model-fitting established that cluding CRISPLD2, DMBT1, GAS1, and SOCS3, have putative jpet.aspetjournals.org the long-acting b2-adrenoceptor agonists (LABA) indacaterol, anti-inflammatory, antibacterial, and/or antiviral activity. Numer- salmeterol, formoterol, and picumeterol were full agonists on ous indacaterol-regulated genes were also induced or repressed BEAS-2B cells transfected with a cAMP-response element in BEAS-2B cells and human primary bronchial epithelial cells by reporter but differed in efficacy (indacaterol $ formoterol .
    [Show full text]
  • Identification of Key Genes and Pathways for Alzheimer's Disease
    Biophys Rep 2019, 5(2):98–109 https://doi.org/10.1007/s41048-019-0086-2 Biophysics Reports RESEARCH ARTICLE Identification of key genes and pathways for Alzheimer’s disease via combined analysis of genome-wide expression profiling in the hippocampus Mengsi Wu1,2, Kechi Fang1, Weixiao Wang1,2, Wei Lin1,2, Liyuan Guo1,2&, Jing Wang1,2& 1 CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China 2 Department of Psychology, University of Chinese Academy of Sciences, Beijing 10049, China Received: 8 August 2018 / Accepted: 17 January 2019 / Published online: 20 April 2019 Abstract In this study, combined analysis of expression profiling in the hippocampus of 76 patients with Alz- heimer’s disease (AD) and 40 healthy controls was performed. The effects of covariates (including age, gender, postmortem interval, and batch effect) were controlled, and differentially expressed genes (DEGs) were identified using a linear mixed-effects model. To explore the biological processes, func- tional pathway enrichment and protein–protein interaction (PPI) network analyses were performed on the DEGs. The extended genes with PPI to the DEGs were obtained. Finally, the DEGs and the extended genes were ranked using the convergent functional genomics method. Eighty DEGs with q \ 0.1, including 67 downregulated and 13 upregulated genes, were identified. In the pathway enrichment analysis, the 80 DEGs were significantly enriched in one Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, GABAergic synapses, and 22 Gene Ontology terms. These genes were mainly involved in neuron, synaptic signaling and transmission, and vesicle metabolism. These processes are all linked to the pathological features of AD, demonstrating that the GABAergic system, neurons, and synaptic function might be affected in AD.
    [Show full text]
  • Targeted Disruption of the Adducin Gene ( Add2) Causes Red Blood Cell
    Proc. Natl. Acad. Sci. USA Vol. 96, pp. 10717–10722, September 1999 Cell Biology Targeted disruption of the ␤ adducin gene (Add2) causes red blood cell spherocytosis in mice DIANA M. GILLIGAN*†,LARISSA LOZOVATSKY*, BABETTE GWYNN‡,CARLO BRUGNARA§,NARLA MOHANDAS¶, AND LUANNE L. PETERS‡ *Department of Internal Medicine (Hematology), Yale University School of Medicine, New Haven, CT 06510; ‡The Jackson Laboratory, Bar Harbor, ME 04609; §Department of Laboratory Medicine, Children’s Hospital, Boston, MA 02115; and ¶Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720 Communicated by Edward A. Adelberg, Yale University, New Haven, CT, July 8, 1999 (received for review May 25, 1999) ABSTRACT Adducins are a family of cytoskeleton pro- was analyzed by Southern blotting using a flanking EcoRV- teins encoded by three genes (␣, ␤, ␥). In a comprehensive EcoRI fragment as the hybridization probe (Fig. 3B). Blasto- assay of gene expression, we show the ubiquitous expression cyst injection and embryo transfer were performed by using of ␣- and ␥-adducins in contrast to the restricted expression standard techniques (13). Male chimeras were mated to of ␤-adducin. ␤-adducin is expressed at high levels in brain C57BL͞6J females to generate heterozygotes. Progeny were and hematopoietic tissues (bone marrow in humans, spleen in genotyped by using PCR on tail biopsies. mice). To elucidate adducin’s role in vivo, we created ␤-ad- Red Blood Cell Analysis. Blood counts were determined by ducin null mice by gene targeting, deleting exons 9–13. A using a Technicon H3 analyzer (Bayer Diagnostics, Tarrytown, 55-kDa chimeric polypeptide is produced from the first eight NY). Smears were stained with Wright-Giemsa (Sigma).
    [Show full text]
  • Dysferlin, a Novel Skeletal Muscle Gene, Is Mutated in Miyoshi Myopathy and Limb Girdle Muscular Dystrophy
    © 1998 Nature America Inc. • http://genetics.nature.com article Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy Jing Liu1,11, Masashi Aoki1, Isabel Illa2, Chenyan Wu3, Michel Fardeau4, Corrado Angelini5, Carmen Serrano2, J. Andoni Urtizberea4, Faycal Hentati6, Mongi Ben Hamida6, Saeed Bohlega7, Edward J. Culper7, Anthony A. Amato8, Karen Bossie1, Joshua Oeltjen1, Khemissa Bejaoui1, Diane McKenna-Yasek1, Betsy A. Hosler1, Erwin Schurr9, Kiichi Arahata10, Pieter J. de Jong3 & Robert H. Brown Jr1 Miyoshi myopathy (MM) is an adult onset, recessive inherited distal muscular dystrophy that we have mapped to human chromosome 2p13. We recently constructed a 3-Mb P1-derived artificial chromosome (PAC) contig spanning the MM candidate region. This clarified the order of genetic markers across the MM locus, provided five new poly- morphic markers within it and narrowed the locus to approximately 2 Mb. Five skeletal muscle expressed sequence tags (ESTs) map in this region. We report that one of these is located in a novel, full-length 6.9-kb muscle cDNA, and we designate the corresponding protein ‘dysferlin’. We describe nine mutations in the dysferlin gene in nine families; five are predicted to prevent dysferlin expression. Identical mutations in the dysferlin gene can produce more than one myopathy phenotype (MM, limb girdle dystrophy, distal myopathy with anterior tibial onset). Introduction order discrepancies in previous studies6,8,13. The physical size of http://genetics.nature.com • Autosomal recessive muscular dystrophies constitute a genetically the PAC contig also indicated that the previous minimal size esti- heterogeneous group of disorders1−3.
    [Show full text]
  • Mouse Add2 Conditional Knockout Project (CRISPR/Cas9)
    https://www.alphaknockout.com Mouse Add2 Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Add2 conditional knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Add2 gene (NCBI Reference Sequence: NM_001271858 ; Ensembl: ENSMUSG00000030000 ) is located on Mouse chromosome 6. 16 exons are identified, with the ATG start codon in exon 3 and the TGA stop codon in exon 16 (Transcript: ENSMUST00000204059). Exon 3 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the Mouse Add2 gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-434N19 as template. Cas9, gRNA and targeting vector will be co-injected into fertilized eggs for cKO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Mice homozygous for targeted mutations that inactivate the gene display mild anemia with compensated hemolysis, marked alteration in osmotic fragility, predominant presence of elliptocytes in the blood and increased blood pressure. Exon 3 starts from about 100% of the coding region. The knockout of Exon 3 will result in frameshift of the gene. The size of intron 2 for 5'-loxP site insertion: 3014 bp, and the size of intron 3 for 3'-loxP site insertion: 859 bp. The size of effective cKO region: ~683 bp. The cKO region does not have any other known gene. Page 1 of 8 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele gRNA region 5' gRNA region 3' 1 3 4 16 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Exon of mouse Add2 Homology arm cKO region loxP site Page 2 of 8 https://www.alphaknockout.com Overview of the Dot Plot Window size: 10 bp Forward Reverse Complement Sequence 12 Note: The sequence of homologous arms and cKO region is aligned with itself to determine if there are tandem repeats.
    [Show full text]
  • Pharmacogenomics and Pharmacogenetics of Hypertension: Update and Perspectives—The Adducin Paradigm
    Pharmacogenomics and Pharmacogenetics of Hypertension: Update and Perspectives—The Adducin Paradigm Paolo Manunta and Giuseppe Bianchi Division of Nephrology, Dialysis and Hypertension, University “Vita-Salute” San Raffaele Hospital, Milan, Italy There is a growing literature on the potential prospective use of genome information to enhance success in finding new medicines. An example of a prospective efficacy of pharmacogenetic and pharmacogenomics is the detection and impact of adducin polymorphism on hypertension. Adducin is a heterodimeric cytoskeleton protein, the three subunits of which are encoded by genes (ADD1, ADD2, and ADD3) that map to three different chromosomes. A long series of parallel studies in the Milan hypertensive rat strain model of hypertension and humans indicated that an altered adducin function might cause hypertension through an enhanced constitutive tubular sodium reabsorption. In particular, six linkage studies, 18 of 20 association studies, and four of five follow-up studies that measured organ damage in hypertensive patients support the clinical impact of adducing polymorphism. As many modulatory genes and environment affect the adducin activity, the context must be taken into account to measure the clinical effect size of adducins. Pharmacogenomics is giving an important contribution to this end. In particular, the selective advantages of diuretics in preventing myocardial infarction and stroke over other antihypertensive therapies that produce a similar BP reduction in carriers of the mutated adducin may support new strategies that aim to optimize the use of antihypertensive agents for the prevention of hypertension-associated organ damage. J Am Soc Nephrol 17: S30–S35, 2006. doi: 10.1681/ASN.2005121346 he enormous variation in the individual response to optimal goal levels seems to be more important than specific antihypertensive treatment has led to acceleration of drug selection.
    [Show full text]
  • Molecular Mechanisms of Dendrite Stability
    REVIEWS Molecular mechanisms of dendrite stability Anthony J. Koleske Abstract | In the developing brain, dendrite branches and dendritic spines form and turn over dynamically. By contrast, most dendrite arbors and dendritic spines in the adult brain are stable for months, years and possibly even decades. Emerging evidence reveals that dendritic spine and dendrite arbor stability have crucial roles in the correct functioning of the adult brain and that loss of stability is associated with psychiatric disorders and neurodegenerative diseases. Recent findings have provided insights into the molecular mechanisms that underlie long-term dendrite stabilization, how these mechanisms differ from those used to mediate structural plasticity and how they are disrupted in disease. The proper formation and long-term maintenance of as it affords mature neurons the ability to fine-tune spine- neuronal connectivity is crucial for correct function- based synaptic connections, while retaining overall long- ing of the brain. The size and shape of a neuron’s den- term dendrite arbor field integrity and integration within drite arbor determine the number and distribution of networks. Furthermore, cytoskeletal stability is crucial receptive synaptic contacts it can make with afferents. for maintaining long-lasting synaptic changes such as During development, dendrites undergo continual long-term potentiation (LTP). Examining the distinct dynamic changes in shape to facilitate proper wiring, mechanisms that mediate spine and dendrite stability is synapse formation and establishment of neural circuits. the major focus of this Review. Dendrite arbors are highly dynamic during develop- By adulthood, the dynamic behaviour of spines is ment, extending and retracting branches as they mature, greatly reduced.
    [Show full text]
  • Original Article Common Variant Rs7597774 in ADD2 Is Associated with Dilated Cardiomyopathy in Chinese Han Population
    Int J Clin Exp Med 2015;8(1):1188-1196 www.ijcem.com /ISSN:1940-5901/IJCEM0003312 Original Article Common variant rs7597774 in ADD2 is associated with dilated cardiomyopathy in Chinese Han population Fei F Chen1*, Yun L Xia1*, Cheng Q Xu2, Si S Li2, Yuan Y Zhao2, Xiao J Wang2, Shan S Chen2, Lian J Gao1, Yang Zhong3, Xin Tu2, Qing Wang2,4, Yan Z Yang1 1Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, China; 2College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technol- ogy, Wuhan, China; 3Department of Cardiology, Fifth People’s Hospital of Dalian, Dalian, China; 4Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. *Equal contributors. Received October 21, 2014; Accepted January 7, 2015; Epub January 15, 2015; Published January 30, 2015 Abstract: Two polymorphisms, rs7597774 and rs1739843 in ADD2 and HSPB7 respectively, were found to be as- sociated with dilated cardiomyopathy (DCM) in European cohorts but the results were not validated in the Chinese Han population. We aimed to test the association of the two variants with DCM in a cohort of Chinese Han popula- tion. DCM (399) and control (1384) individuals were identified from the GeneID database in China, and DNA was isolated from peripheral blood lymphocytes for genotyping. Alleles were amplified by PCR, and amplicons harboring polymorphisms rs1739843 and rs7597774 were directly genotyped using high-resolution melting analysis. Sta- tistical analysis was subsequently performed to evaluate the association of the variants with DCM.
    [Show full text]
  • Cortical Organoids Model Early Brain Development Disrupted by 16P11.2 Copy
    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.25.172262; this version posted October 6, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Cortical Organoids Model Early Brain Development Disrupted by 16p11.2 Copy Number Variants in Autism Jorge Urresti1#, Pan Zhang1#, Patricia Moran-Losada1, Nam-Kyung Yu2, Priscilla D. Negraes3,4, Cleber A. Trujillo3,4, Danny Antaki1,3, Megha Amar1, Kevin Chau1, Akula Bala Pramod1, Jolene Diedrich2, Leon Tejwani3,4, Sarah Romero3,4, Jonathan Sebat1,3,5, John R. Yates III2, Alysson R. Muotri3,4,6,7,*, Lilia M. Iakoucheva1,* 1 Department of Psychiatry, University of California San Diego, La Jolla, CA, USA 2 Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA 3 Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA USA 4 Department of Pediatrics/Rady Children’s Hospital San Diego, University of California, San Diego, La Jolla, CA, USA 5 University of California San Diego, Beyster Center for Psychiatric Genomics, La Jolla, CA, USA 6 University of California San Diego, Kavli Institute for Brain and Mind, La Jolla, CA, USA 7 Center for Academic Research and Training in Anthropogeny (CARTA), La Jolla, CA, USA # These authors contributed equally: Jorge Urresti, Pan Zhang *Corresponding authors: Lilia M. Iakoucheva ([email protected]) and Alysson R. Muotri ([email protected]). 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.25.172262; this version posted October 6, 2020.
    [Show full text]
  • Transcriptional Profile of Human Anti-Inflamatory Macrophages Under Homeostatic, Activating and Pathological Conditions
    UNIVERSIDAD COMPLUTENSE DE MADRID FACULTAD DE CIENCIAS QUÍMICAS Departamento de Bioquímica y Biología Molecular I TESIS DOCTORAL Transcriptional profile of human anti-inflamatory macrophages under homeostatic, activating and pathological conditions Perfil transcripcional de macrófagos antiinflamatorios humanos en condiciones de homeostasis, activación y patológicas MEMORIA PARA OPTAR AL GRADO DE DOCTOR PRESENTADA POR Víctor Delgado Cuevas Directores María Marta Escribese Alonso Ángel Luís Corbí López Madrid, 2017 © Víctor Delgado Cuevas, 2016 Universidad Complutense de Madrid Facultad de Ciencias Químicas Dpto. de Bioquímica y Biología Molecular I TRANSCRIPTIONAL PROFILE OF HUMAN ANTI-INFLAMMATORY MACROPHAGES UNDER HOMEOSTATIC, ACTIVATING AND PATHOLOGICAL CONDITIONS Perfil transcripcional de macrófagos antiinflamatorios humanos en condiciones de homeostasis, activación y patológicas. Víctor Delgado Cuevas Tesis Doctoral Madrid 2016 Universidad Complutense de Madrid Facultad de Ciencias Químicas Dpto. de Bioquímica y Biología Molecular I TRANSCRIPTIONAL PROFILE OF HUMAN ANTI-INFLAMMATORY MACROPHAGES UNDER HOMEOSTATIC, ACTIVATING AND PATHOLOGICAL CONDITIONS Perfil transcripcional de macrófagos antiinflamatorios humanos en condiciones de homeostasis, activación y patológicas. Este trabajo ha sido realizado por Víctor Delgado Cuevas para optar al grado de Doctor en el Centro de Investigaciones Biológicas de Madrid (CSIC), bajo la dirección de la Dra. María Marta Escribese Alonso y el Dr. Ángel Luís Corbí López Fdo. Dra. María Marta Escribese
    [Show full text]
  • Adducin in Tumorigenesis and Metastasis
    www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 29), pp: 48453-48459 Review Adducin in tumorigenesis and metastasis Cong Luo1 and Jiayu Shen2 1Zhejiang Cancer Hospital, Department of Abdominal oncology, Hangzhou, Zhejiang, China 2Zhejiang Chinese Medical University, The Second Clinical Medical College, Hangzhou, Zhejiang, China Correspondence to: Cong Luo, email: [email protected] Keywords: adducin, phosphorylation, tumor Received: November 16, 2016 Accepted: March 28, 2017 Published: April 18, 2017 Copyright: Luo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Adducin is a membrane-skeletal protein localized at spectrin-actin junctions, involving in the formation of the network of cytoskeleton, cellular signal transduction, ionic transportation, cell motility and cell proliferation. While previous researches focused mainly on the relationship between adducin and hypertension, there are few studies focusing on the role of adducin in tumor. Previous studies showed that adducin played a role in the evolution and progression of neoplasm. This review makes a brief summary on the structure, function and mechanism of adducin and how adducin functions in tumorigenesis and metastasis. INTRODUCTION Human ADD2 is localized at chromosome 2p13-p14 [5], whereas ADD3 is on chromosome 10q24.2-24.3[6]. Adducin is a ubiquitously expressed membrane- The sequences of α adducin and β adducin share 66% skeletal protein, which was firstly extracted from human similarity at amino acid level, while γ adducin displays erythrocyte in 1986 [1].
    [Show full text]