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41.
H?Bukulmez AL?Matthews CM?Sullivan C?Chen MJ?Kraay RC?Elston RW?Moskowitz VM?Goldberg ML?WarmanEmail author 《Arthritis research & therapy》2005,8(1):R25
In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA),
we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family
histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses
to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis
of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing
total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We
compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings
of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the
siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age
and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to
identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with
hip OA than in those with knee OA. 相似文献
42.
The restriction enzyme TaqI digests 0.2% of the genomic DNA from the
grasshopper Caledia captiva to a family of sequences 168 bp in length
(length of consensus sequence). The sequence variation of this "Taq family"
of repeat units was examined among four races from C. captiva to assay the
pattern of evolution within this highly repeated DNA. The Taq-family
repeats are located in C-banded heterochromatin on at least one member of
each homologous pair of chromosomes; the locations range from centromeric
to telomeric. Thirty-nine cloned repeats isolated from two population 1A
individuals along with 11 clones from seven populations taken from three of
the races demonstrated sequence variation at 72 positions. Pairwise
comparisons of the cloned repeats, both within an individual and between
different races, indicate that levels of intraspecific divergence, as
measured by reproductive incompatibility, do not correlate with sequence
divergence among the 168-bp repeats. A number of subsequences within the
repeat remain unchanged among all 50 clones; the longest of these is 18 bp.
That the same 18-bp subsequence is present in all clones examined is a
finding that departs significantly (P less than 0.01) from what would be
expected to occur at random. Two other cloned repeats, from a
reproductively isolated race of C. captiva, have sequences that show 56%
identity with this 18-bp conserved region. An analysis showed that the
frequency of occurrence of an RsaI recognition site within the 168- bp
repeat in the entire Taq family agreed with that found in the cloned
sequences. These data, along with a partial sequence for the entire Taq
family obtained by sequencing uncloned repeats, suggest that the consensus
sequence from the cloned copies is representative of this highly repeated
family and is not a biased sample resulting from the cloning procedure. The
18-bp conserved sequence is part of a 42-bp sequence that possesses dyad
symmetry typical of protein-binding sites. We speculate that this may be
significant in the evolution of the Taq family of sequences.
相似文献
43.
Stamos B Loredo L Chand S Phan TV Zhang Y Mohapatra S Rajeshwar K Perera R 《Analytical biochemistry》2012,424(2):114-123
Protein microarrays have emerged as an indispensable research tool for providing information about protein functions and interactions through high-throughput screening. Traditional methods for immobilizing biomolecules onto solid surfaces have been based on covalent and noncovalent binding, entrapment in semipermeable membranes, microencapsulation, sol gel, and hydrogel methods. Each of these techniques has its own strengths but fails to combine the most important tenets of a functional protein microarray such as covalent attachment, native protein conformation, homogeneity of the protein monolayer, control over active site orientation, and retention of protein activity. Here we present a selective and site-directed covalent immobilization technique for proteins via a benzoxazine ring formation through a Diels-Alder reaction in water and a genetically encoded 3-amino-L-tyrosine (3-NH(2)Tyr) amino acid. Fully functional protein microarrays, with monolayer arrangements and complete control over their orientations, were generated using this strategy. 相似文献
44.
Increased plasticity of genomic imprinting of Dlk1 in brain is due to genetic and epigenetic factors
Sylvie Croteau David Roquis Marie-Claude Charron Danielle Frappier Daniel Yavin J. Conceptión Loredo–Osti Thomas J. Hudson Anna K. Naumova 《Mammalian genome》2005,16(2):127-135
The expression of six imprinted genes (Dlk1, Gtl2, Igf2r, Kcnq1, Nnat, and Peg1) was examined in brains of 21 mice derived from N2 × N2 intercrosses between C57BL/6 and MOLF/Ei strains. Imprinting of Igf2r, Kcnq1, Gtl2, and Dlk1 varied among individuals. As three of these genes are implicated in cell–cell signaling or cell–environment interactions, variation in their imprinting may influence a wide range of biological processes from cell differentiation to behavior. To elucidate the mechanisms underlying the interindividual imprinting variation in the brain, we focused our effort on the paternally expressed gene Dlk1. We investigated expression of Dlk1 in the brains of animals from N9 and N10 backcrosses and found that reactivation of the normally silent maternal Dlk1 allele in the N9 and N10 mice occurred less often than in N2 × N2 animals. Our data suggest that trans-acting genetic factors of MOLF/Ei origin facilitate the reactivation of the normally silent maternal allele of Dlk1. We mapped one of these factors to the proximal part of Chr 7. The results of bisulfite sequencing methylation analysis show that reactivation of the maternal allele was also associated with hypermethylation of the intragenic differentially methylated region (IG DMR), which is the imprinting control region for the Dlk1–Gtl2 domain. Thus, the imprinting status of Dlk1 in the brain depends upon trans-acting genetic influences and correlates with the methylation status of a specific subregion of the IG DMR.The GenBank accession numbers for sequences described in this article are AY644388–644394. 相似文献
45.
Intercalation of proflavine and a platinum derivative of proflavine into double-helical Poly(A)
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The equilibria and kinetics of the interactions of proflavine (PR) and its platinum-containing derivative [PtCl(tmen)(2)HNC(13)H(7)(NHCH(2)CH(2))(2)](+) (PRPt) with double-stranded poly(A) have been investigated by spectrophotometry and Joule temperature-jump relaxation at ionic strength 0.1 M, 25 degrees C, and pH 5.2. Spectrophotometric measurements indicate that base-dye interactions are prevailing. T-jump experiments with polarized light showed that effects due to field-induced alignment could be neglected. Both of the investigated systems display two relaxation effects. The kinetic features of the reaction are discussed in terms of a two-step series mechanism in which a precursor complex DS(I) is formed in the fast step, which is then converted to a final complex in the slow step. The rate constants of the fast step are k(1) = (2.5 +/- 0.4) x 10(6) M(-1) s(-1), k(-1) = (2.4 +/- 0.1) x 10(3) s(-1) for poly(A)-PR and k(1) = (2.3 +/- 0.1) x 10(6) M(-1) s(-1), k(-1) = (1.6 +/- 0.2) x 10(3) s(-1) for poly(A)-PRPt. The rate constants for the slow step are k(2) = (4.5 +/- 0.5) x 10(2) s(-1), k(-2) = (1.7 +/- 0.1) x 10(2) s(-1) for poly(A)-PR and k(2) = 9.7 +/- 1.2 s(-1), k(-2) = 10.6 +/- 0.2 s(-1) for poly(A)-PRPt. Spectrophotometric measurements yield for the equilibrium constants and site size the values K = (4.5 +/- 0.1) x 10(3) M(-1), n = 1.3 +/- 0.5 for poly(A)-PR and K = (2.9 +/- 0.1) x 10(3) M(-1), n = 2.3 +/- 0.6 for poly(A)-PRPt. The values of k(1) are similar and lower than expected for diffusion-limited reactions. The values of k(-1) are similar as well. It is suggested that the formation of DS(I) involves only the proflavine residues in both systems. In contrast, the values of k(2) and k(-2) in poly(A)-PRPt are much lower than in poly(A)-PR. The results suggest that in the complex DS(II) of poly(A)-PRPt both proflavine and platinum residues are intercalated. In addition, a very slow process was detected and ascribed to the covalent binding of Pt(II) to the adenine. 相似文献
46.
Julio Isael Pérez-Carreón Lidia Martínez-Pérez María Lilia Loredo Lucia Yañez-Maldonado Gabriela Velasco-Loyden Susana Vidrio-Gómez Jorge Ramírez-Salcedo Francisco Hernández-Luis Israel Velázquez-Martínez Juan Antonio Suárez-Cuenca Rolando Hernández-Muñoz Victoria Chagoya de Sánchez 《The international journal of biochemistry & cell biology》2010,42(2):287-296
47.
Repeated evolution of sympatric,palaeoendemic species in closely related,co‐distributed lineages of Hemiphyllodactylus Bleeker, 1860 (Squamata: Gekkonidae) across a sky‐island archipelago in Peninsular Malaysia
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L. Lee Grismer Perry L. Wood Jr Shahrul Anuar Evan S. H. Quah Mohd Abdul Muin Chan Kin Onn Alexandra X. Sumarli Ariel I. Loredo 《Zoological Journal of the Linnean Society》2015,174(4):859-876
A time‐calibrated phylogenetic tree indicates that the evolution of sympatric, montane, endemic species from closely related, co‐distributed lineages of the Hemiphyllodactylus harterti group were not the result of rapid, forest‐driven, climatic oscillations of the Last Glacial Maximum, but rather the result of infrequent episodes of environmental fluctuation during the Late Miocene. This hypothesis is supported by genetic divergences (based on the mitochondrial gene ND2) between the three major lineages of the H. harterti group (17.5–25.1%), their constituent species (9.4–14.3%), and the evolution of discrete, diagnostic, morphological, and colour pattern characteristics between each species. Sister species pairs from two of the three lineages occur in sympatry on mountain tops from opposite sides of the Thai–Malay Peninsula, but the lineages to which each pair belongs are not sister lineages. A newly discovered species from Gunung Tebu, Terengganu State, H emiphyllodactylus bintik sp. nov. , is described. © 2015 The Linnean Society of London 相似文献
48.
Josimari M DeSantana Kamilla ML da Cruz Kathleen A Sluka 《Arthritis research & therapy》2013,15(6):222
Animal models of disease states are valuable tools for developing new treatments and investigating underlying mechanisms. They should mimic the symptoms and pathology of the disease and importantly be predictive of effective treatments. Fibromyalgia is characterized by chronic widespread pain with associated co-morbid symptoms that include fatigue, depression, anxiety and sleep dysfunction. In this review, we present different animal models that mimic the signs and symptoms of fibromyalgia. These models are induced by a wide variety of methods that include repeated muscle insults, depletion of biogenic amines, and stress. All potential models produce widespread and long-lasting hyperalgesia without overt peripheral tissue damage and thus mimic the clinical presentation of fibromyalgia. We describe the methods for induction of the model, pathophysiological mechanisms for each model, and treatment profiles. 相似文献
49.
Ariadna Yolanda Ruiz‐Loredo Edith López Ana María López‐Colomé 《Journal of cellular physiology》2011,226(2):414-423
The retinal pigment epithelium (RPE) forms the outer blood–retina barrier (BRB). Most retinal diseases involve BRB breakdown, whereupon thrombin contained in serum directly contacts the RPE. Thrombin is known to promote actin stress fiber formation, an important determinant in eye diseases involving the epithelial–mesenchymal transition (EMT) and migration of RPE cells, such as proliferative vitreoretinopathy. We analyzed thrombin effect on signaling pathways leading to myosin light chain (MLC) phosphorylation and actin stress fiber formation in primary cultures of rat RPE cells, in order to support a role for thrombin in RPE transdifferentiation. MLC phosphorylation was measured by Western blot; actin cytoskeleton was visualized using immunofluorescent phalloidin, and Rho GTPase activation was assessed by ELISA. We showed that thrombin/PAR‐1 induces the time‐ and dose‐dependent phosphorylation of MLC through the activation of Rho/ROCK and myosin light chain kinase (MLCK). ROCK increased phospho‐MLC by phosphorylating MLC and by inhibiting MLC phosphatase. Thrombin effect was abolished by the ROCK inhibitor Y‐27632, whereas MLCK inhibitor ML‐7 and PLC‐β inhibitor U73122 attenuated MLC phosphorylation by ≈50%, suggesting the activation of MLCK by PLC‐β‐mediated calcium increase. Additionally, thrombin‐induced MLC phosphorylation was blocked by the inhibitory PKCζ pseudosubstrate, wortmannin, and LY294002, indicating IP3/PKCζ involvement in the control of MLC phosphorylation. Moreover, we demonstrated that thrombin effect on MLC induces actin stress fiber formation, since this effect was prevented by inhibiting the pathways leading to MLC phosphorylation. We conclude that thrombin stimulation of MLC phosphorylation and actin stress fiber formation may be involved in thrombin‐induced RPE cell transformation subsequent to BRB dysfunction. J. Cell. Physiol. 226: 414–423, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
50.
Jennifer L. Shea J. Concepción Loredo‐Osti Guang Sun 《Obesity (Silver Spring, Md.)》2010,18(7):1393-1397
Retinol‐binding protein 4 (RBP4) is a novel adipokine that likely contributes to systemic insulin resistance and dyslipidemia. The role of genetic variations in RBP4 on phenotypes of glucose and lipid metabolism is not clear in humans. The purpose of this study was to examine five single‐nucleotide polymorphisms (SNPs) in the RBP4 gene to determine their relationship with markers of insulin resistance and serum lipids in the CODING Study. The CODING Study consists of 1,836 subjects recruited from the genetically homogeneous population of Newfoundland and Labrador (NL), Canada. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMAIR), HOMA for β cell function (HOMAβ), total cholesterol (Chol), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), and triglycerides were determined after a 12‐h fast. Five SNPs within RBP4 (rs3758539, G/A 5′ flanking region; rs61461737, A/G intron; rs10882280, C/A intron; rs11187545, A/G intron; and rs12265684, C/G intron) were genotyped using TaqMan validated or functionally tested SNP genotyping assays. After correcting for multiple testing, we observed a significant association between the minor allele of two noncoding SNPs (rs10882280 and rs11187545) and higher serum HDL‐C (P = 0.043 and 0.042, respectively). No significant associations were observed with any other parameter related to lipid metabolism. We also found no significant association between any variant sites and markers of insulin resistance. Our results suggest that genetic variations in RBP4 may play a role in the differences in serum HDL‐C levels in the NL population. 相似文献