WorldWideScience

Sample records for allele separating skeletal

  1. Allele-specific gene silencing in two mouse models of autosomal dominant skeletal myopathy.

    Directory of Open Access Journals (Sweden)

    Ryan E Loy

    Full Text Available We explored the potential of mutant allele-specific gene silencing (ASGS in providing therapeutic benefit in two established mouse models of the autosomal dominantly-inherited muscle disorders, Malignant Hyperthermia (MH and Central Core Disease (CCD. Candidate ASGS siRNAs were designed and validated for efficacy and specificity on ryanodine receptor (RyR1 cDNA mini-constructs expressed in HEK293 cells using RT-PCR- and confocal microscopy-based assays. In vivo delivery of the most efficacious identified siRNAs into flexor digitorum brevis (FDB muscles was achieved by injection/electroporation of footpads of 4-6 month old heterozygous Ryr1(Y524S/+ (YS/+ and Ryr1(I4895T/+ (IT/+ knock-in mice, established mouse models of MH with cores and CCD, respectively. Treatment of IT/+ mice resulted in a modest rescue of deficits in the maximum rate (∼38% rescue and magnitude (∼78% of ligand-induced Ca(2+ release that occurred in the absence of a change in the magnitude of electrically-evoked Ca(2+ release. Compared to the difference between the caffeine sensitivity of Ca(2+ release in FDB fibers from YS/+ and WT mice treated with SCR siRNA (EC(50: 1.1 mM versus 4.4 mM, respectively, caffeine sensitivity was normalized in FDB fibers from YS/+ mice following 2 (EC(50: 2.8 mM and 4 week (EC(50: 6.6 mM treatment with YS allele-specific siRNA. Moreover, the temperature-dependent increase in resting Ca(2+ observed in FDB fibers from YS/+ mice was normalized to WT levels after 2 weeks of treatment with YS allele-specific siRNA. As determined by quantitative real time PCR, the degree of functional rescue in YS/+ and IT/+ mice correlated well with the relative increase in fractional WT allele expression.

  2. Enhanced protein electrophoresis technique for separating human skeletal muscle myosin heavy chain isoforms

    Science.gov (United States)

    Bamman, M. M.; Clarke, M. S.; Talmadge, R. J.; Feeback, D. L.

    1999-01-01

    Talmadge and Roy (J. Appl. Physiol. 1993, 75, 2337-2340) previously established a sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) protocol for separating all four rat skeletal muscle myosin heavy chain (MHC) isoforms (MHC I, IIa, IIx, IIb); however, when applied to human muscle, the type II MHC isoforms (Ila, IIx) are not clearly distinguished. In this brief paper we describe a modification of the SDS-PAGE protocol which yields distinct and consistent separation of all three adult human MHC isoforms (MHC I, IIa, IIx) in a minigel system. MHC specificity of each band was confirmed by Western blot using three monoclonal IgG antibodies (mAbs) immunoreactive against MHCI (mAb MHCs, Novacastra Laboratories), MHCI+IIa (mAb BF-35), and MHCIIa+IIx (mAb SC-71). Results provide a valuable SDS-PAGE minigel technique for separating MHC isoforms in human muscle without the difficult task of casting gradient gels.

  3. Functional reconstitution of skeletal muscle Ca2+ channels: Separation of regulatory and channel components

    International Nuclear Information System (INIS)

    Regulatory properties of a partially purified Ca2+-channel preparation from isolated rabbit skeletal muscle triads were examined in proteoliposomes. By selective reconstitution of protein fractions obtained by wheat germ lectin and ion-exchange chromatography, a separation of Ca2+-channel activity (fraction C) from regulatory component(s) (fraction R) responsible for verapamil sensitivity was achieved. Reconstitution of fraction C alone yielded vesicles that exhibited channel-mediated 45Ca2+ uptake that could be directly inhibited by coreconstitution of G0 in the presence of guanosine 5'-[γ-thio]triphosphate. Coreconstitution of fractions C and R yielded vesicles in which the sensitivity of 45Ca2+ uptake to verapamil was restored. Fraction C included a 180-kDa protein that was phosphorylated by cAMP-dependent protein kinase (PK-A) but not by PK-P and a 145-kDa protein that was not phosphorylated by either kinase. Fraction R contained proteins that did not absorb to wheat germ lectin and included 165-kDa and 55-kDa proteins that were phosphorylated by PK-P but not by PK-A. These results suggest a complex model for Ca2+-channel regulation in skeletal muscle involving a number of distinct, separable protein components

  4. Skeletal muscle

    Science.gov (United States)

    There are approximately 650-850 muscles in the human body these include skeletal (striated), smooth and cardiac muscle. The approximation is based on what some anatomists consider separate muscle or muscle systems. Muscles are classified based on their anatomy (striated vs. smooth) and if they are v...

  5. Regulation of protein synthesis in human skeletal muscle : separate and combined effects of exercise and amino acids

    OpenAIRE

    Apró, William

    2014-01-01

    Skeletal muscle is a highly plastic tissue which has the ability to adapt to various forms of external stimuli such as diverse modes of contractile activity. Thus, performance of endurance exercise over several of weeks results in increased oxidative capacity. In contrast, prolonged performance of resistance exercise ultimately results in increased muscle mass. These adaptations are brought about by transient alterations in gene expression and mRNA translation which result...

  6. The FOXO3A rs2802292 G-Allele Associates with Improved Peripheral and Hepatic Insulin Sensitivity and Increased Skeletal Muscle-FOXO3A mRNA Expression in Twins

    DEFF Research Database (Denmark)

    Banasik, Karina; Ribel-Madsen, Rasmus; Gjesing, Anette P;

    2011-01-01

    with reduced incremental area under the curve 0–120 min for insulin after an oral glucose load [ß = -3% (-5; -0.07), P = 0.04], but this association was not significant after adjustment for body mass index. Conclusion: Our data indicate that the minor G-allele of FOXO3A rs2802292 is associated with enhanced...

  7. What phylogeny and gene genealogy analyses reveal about homoplasy in citrus microsatellite alleles

    OpenAIRE

    Barkley, Noelle A.; Krueger, Robert R.; Federici, Claire T.; Roose, Mikeal L

    2009-01-01

    Sixty-five microsatellite alleles amplified from ancestral citrus accessions classified in three separate genera were evaluated for sequence polymorphism to establish the basis of inter- and intra-allelic genetic variation, evaluate the extent of size homoplasy, and determine an appropriate model (stepwise or infinite allele) for analysis of citrus microsatellite alleles. Sequences for each locus were aligned and subsequently used to determine relationships between alleles of different taxa v...

  8. Nomenclature for human CYP2D6 alleles.

    Science.gov (United States)

    Daly, A K; Brockmöller, J; Broly, F; Eichelbaum, M; Evans, W E; Gonzalez, F J; Huang, J D; Idle, J R; Ingelman-Sundberg, M; Ishizaki, T; Jacqz-Aigrain, E; Meyer, U A; Nebert, D W; Steen, V M; Wolf, C R; Zanger, U M

    1996-06-01

    To standardize CYP2D6 allele nomenclature, and to conform with international human gene nomenclature guidelines, an alternative to the current arbitrary system is described. Based on recommendations for human genome nomenclature, we propose that alleles be designated by CYP2D6 followed by an asterisk and a combination of roman letters and arabic numerals distinct for each allele with the number specifying the key mutation and, where appropriate, a letter specifying additional mutations. Criteria for classification as a separate allele and protein nomenclature are also presented. PMID:8807658

  9. Allele coding in genomic evaluation

    DEFF Research Database (Denmark)

    Standen, Ismo; Christensen, Ole Fredslund

    2011-01-01

    coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being the best. \\paragraph*{Conclusions:} Different allele coding methods lead to the same inference in the marker-based and equivalent models when a fixed...... effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous...... genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call...

  10. Myogenin Regulates Exercise Capacity and Skeletal Muscle Metabolism in the Adult Mouse

    OpenAIRE

    Flynn, Jesse M.; Eric Meadows; Marta Fiorotto; Klein, William H.

    2010-01-01

    Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were ana...

  11. Three allele combinations associated with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Kulakova Olga G

    2006-07-01

    Full Text Available Abstract Background Multiple sclerosis (MS is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS. Methods 286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion of the DRB1, TNF, LT, TGFβ1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group. Results We identified two previously unknown MS-associated tri-allelic combinations: -509TGFβ1*C, DRB1*18(3, CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2 allele, the microsatellite TNFa9 allele and the biallelic combination CCR5Δ32, DRB1*04 were also reidentified as MS-associated. Conclusion These results represent an independent validation of MS association with DRB1*15(2 and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles.

  12. Assignment of SNP allelic configuration in polyploids using competitive allele-specific PCR: application to citrus triploid progeny

    Science.gov (United States)

    Cuenca, José; Aleza, Pablo; Navarro, Luis; Ollitrault, Patrick

    2013-01-01

    Background Polyploidy is a major component of eukaryote evolution. Estimation of allele copy numbers for molecular markers has long been considered a challenge for polyploid species, while this process is essential for most genetic research. With the increasing availability and whole-genome coverage of single nucleotide polymorphism (SNP) markers, it is essential to implement a versatile SNP genotyping method to assign allelic configuration efficiently in polyploids. Scope This work evaluates the usefulness of the KASPar method, based on competitive allele-specific PCR, for the assignment of SNP allelic configuration. Citrus was chosen as a model because of its economic importance, the ongoing worldwide polyploidy manipulation projects for cultivar and rootstock breeding, and the increasing availability of SNP markers. Conclusions Fifteen SNP markers were successfully designed that produced clear allele signals that were in agreement with previous genotyping results at the diploid level. The analysis of DNA mixes between two haploid lines (Clementine and pummelo) at 13 different ratios revealed a very high correlation (average = 0·9796; s.d. = 0·0094) between the allele ratio and two parameters [θ angle = tan−1 (y/x) and y′ = y/(x + y)] derived from the two normalized allele signals (x and y) provided by KASPar. Separated cluster analysis and analysis of variance (ANOVA) from mixed DNA simulating triploid and tetraploid hybrids provided 99·71 % correct allelic configuration. Moreover, triploid populations arising from 2n gametes and interploid crosses were easily genotyped and provided useful genetic information. This work demonstrates that the KASPar SNP genotyping technique is an efficient way to assign heterozygous allelic configurations within polyploid populations. This method is accurate, simple and cost-effective. Moreover, it may be useful for quantitative studies, such as relative allele-specific expression analysis and bulk segregant analysis

  13. Identification of incompatibility alleles in the tetraploid species sour cherry.

    Science.gov (United States)

    Tobutt, K R; Bosković, R; Cerović, R; Sonneveld, T; Ruzić, D

    2004-03-01

    The incompatibility genetics of sour cherry ( Prunus cerasus), an allotetraploid species thought to be derived from sweet cherry (diploid) and ground cherry (tetraploid), were investigated by test crossing and by analysis of stylar ribonucleases which are known to be the products of incompatibility alleles in sweet cherry. Stylar extracts of 36 accessions of sour cherry were separated electrophoretically and stained for ribonuclease activity. The zymograms of most accessions showed three bands, some two or four. Of the ten bands seen, six co-migrated with bands that in sweet cherry are attributed to the incompatibility alleles S(1), S(3), S(4), S(6, ) S(9) and S(13). 'Cacanski Rubin', 'Erdi Botermo B', 'Koros' and 'Ujfehertoi Furtos', which showed bands apparently corresponding to S(1) and S(4), were test pollinated with the sweet cherry 'Merton Late' ( S(1) S(4)). Monitoring pollen tube growth, and, in one case, fruit set, showed that these crosses were incompatible and that the four sour cherries indeed have the alleles S(1) and S(4). Likewise, test pollination of 'Marasca Piemonte', 'Marasca Savena' and 'Morello, Dutch' with 'Noble' ( S(6) S(13)) showed that these three sour cherries have the alleles S(6) and S(13). S(13) was very frequent in sour cherry cultivars, but is rare in sweet cherry cultivars, whereas with S(3) the situation is reversed. It was suggested that the other four bands are derived from ground cherry and one of these, provisionally attributed to S(B), occurred frequently in a small set of ground cherry accessions surveyed. Analysing some progenies from sour by sweet crosses by S allele-specific PCR and monitoring the success of some sweet by sour crosses were informative. They indicated mostly disomic inheritance, with sweet cherry S alleles belonging to one locus and, presumably, the ground cherry alleles to the other, and helped clarify the genomic arrangement of the alleles and the interactions in heteroallelic pollen. PMID:14689184

  14. Multilocus Inherited Neoplasia Alleles Syndrome

    DEFF Research Database (Denmark)

    Whitworth, James; Skytte, Anne-Bine; Sunde, Lone;

    2016-01-01

    as multilocus inherited neoplasia alleles syndrome [MINAS]) in patients with unusual inherited cancer syndrome phenotypes. To facilitate the clinical management of novel cases of MINAS, we have established a database to collect information on what is likely to be an increasingly recognized cohort...

  15. Compatibility of hyaluronic acid hydrogel and skeletal muscle myoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wang Wei; Zhang Li; Sun Liang; Wang Chengyue [Jinzhou Central Hospital, Jinzhou 121000 (China); Fan Ming; Liu Shuhong, E-mail: Weiwang_Ly@yahoo.com.c [Institute of Basic Medical Sciences, Academy of Military Medical Science, Beijing 100850 (China)

    2009-04-15

    Compatibility of hyaluronic acid hydrogel (HAH) and skeletal muscle myoblasts has been investigated for the first time in the present paper. Skeletal muscle myoblasts were separated from skeletons of rats and incubated with a HAH-containing culture medium. Cell morphology, hydrophilicity and cell adhesion of the HAH scaffold were investigated using optical microscopy, scanning electron microscopy, Hoechest33258 fluorescent staining, the immunocytochemistry method and water adsorption rate measurement. It was found that at a proper concentration (around 0.5%) of hyaluronic acid, the hydrogel possessed good compatibility with skeletal muscle myoblasts. The hydrogel can create a three-dimensional structure for the growth of skeletal muscle myoblasts and benefit cell attachment to provide a novel scaffold material for the tissue engineering of skeletal muscle.

  16. Allele walking: a new and highly accurate approach to HLA-DRB1 typing. Application to DRB1*04 alleles.

    Science.gov (United States)

    Nieto, A; Tobes, R; Martín, J; Pareja, E

    1997-02-01

    We have developed a typing method, which can be used even in small laboratories, to produce a highly accurate and reliable allele assignment in any homozygous or heterozygous situation. We have called the method allele walking (AW) and it consists of sequential rounds of PCR-RFLP. After digestion, electrophoresis separates alleles positive for the mutation from the negative alleles; the cleaved fragment is then recovered from the gel and analyzed for mutations at another codon. In this way, AW is able to positively ascertain which mutations are in the same chromosome (cis-linkage) and assigns alleles independently from each other. Artificial sites are created in the PCR step in order to positively detect substitutions not naturally recognized by any of the existing or convenient enzymes. We report the application of AW for typing the 22 DRB1*04 alleles. The first PCR-RFLP round groups DRB1*04 alleles. Subsequently, the mutations at codons 86, 74, 71, 57 and 37 can be analyzed for the unambiguous assignment of the majority of the alleles. Additional polymorphisms at different codons can be assayed to resolve any undetermined alleles. The viability of all the restriction sites used as well as the feasibility of AW were successfully tested. PMID:9062970

  17. Tetra-allelic SNPs: Informative forensic markers compiled from public whole-genome sequence data.

    Science.gov (United States)

    Phillips, C; Amigo, J; Carracedo, Á; Lareu, M V

    2015-11-01

    Multiple-allele single nucleotide polymorphisms (SNPs) are potentially useful for forensic DNA analysis as they can provide more discrimination power than normal binary SNPs. In addition, the presence in a profile of more than two alleles per marker provides a clearer indication of mixed DNA than assessments of imbalanced signals in the peak pairs of binary SNPs. Using the 1000 Genomes Phase III human variant data release of 2014 as the starting point, this study collated 961 tetra-allelic SNPs that pass minimum sequence quality thresholds and where four separate nucleotide substitution alleles were detected. Although most of these loci had three of the four alleles in combined frequencies of 2% or less, 160 had high heterozygosities with 50 exceeding those of 'ideal' 0.5:0.5 binary SNPs. From this set of most polymorphic tetra-allelic SNPs, we identified markers most informative for forensic purposes and explored these loci in detail. Subsets of the most polymorphic tetra-allelic SNPs will make useful additions to current panels of forensic identification SNPs and ancestry-informative SNPs. The 24 most discriminatory tetra-allelic SNPs were estimated to detect more than two alleles in at least one marker per profile in 99.9% of mixtures of African contributors. In European contributor mixtures 99.4% of profiles would show multiple allele patterns, but this drops to 92.6% of East Asian contributor mixtures due to reduced levels of polymorphism for the 24 SNPs in this population group. PMID:26209763

  18. Invasive Allele Spread under Preemptive Competition

    OpenAIRE

    Yasi, J. A.; Korniss, G.; Caraco, T.

    2005-01-01

    We study a discrete spatial model for invasive allele spread in which two alleles compete preemptively, initially only the "residents" (weaker competitors) being present. We find that the spread of the advantageous mutation is well described by homogeneous nucleation; in particular, in large systems the time-dependent global density of the resident allele is well approximated by Avrami's law.

  19. Differential allelic expression of a fibrillin gene (FBNI) in patients with Marfan syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hewett, D.; Lynch, J.; Sykes, B. [Univ. of Oxford (United Kingdom); Firth, H. [Churchill Hospital, Oxford (United Kingdom); Child, A. [St. George`s Hospital Medical School, London (United Kingdom)

    1994-09-01

    Marfan syndrome is a connective-tissue disorder affecting cardiovascular, skeletal, and ocular systems. The major Marfan locus has been identified as the FBN1 gene on chromosome 15; this codes for the extracellular-matrix protein fibrillin, a 350-kD constituent of the 8-10-nm elastin-associated microfibrils. The authors identified five MFS patients who were heterozygous for an RsaI restriction-site dimorphism in the 3{prime} UTR of the FBN1 gene. This expressed variation was used to distinguish the mRNA output from each of the two FBN1 alleles in fibroblast cultures from these five patients. Three of the patients were shown to produce <5% of the normal level of FBN1 transcripts from one of their alleles. This null-allele phenotype was not observed in 10 nonmarfanoid fibroblast cell lines. 26 refs., 4 figs.

  20. The skeletal system

    NARCIS (Netherlands)

    Nikkels, PGJ

    2015-01-01

    Skeletal dysplasias are a group of disorders with a disturbance in development and/or growth of cartilage and/or bone. Epiphysis, metaphysis, and diaphysis of long bones are affected in a generalized manner with or without involvement of membranous bone of the skull. A dysostosis affects one or some

  1. Skeletal (stromal) stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Kermani, Abbas Jafari; Zaher, Walid;

    2015-01-01

    Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells that reside in the bone marrow stroma and can differentiate into osteoblasts, chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC differentiation into osteoblastic cells is a strategy....../preadipocyte factor 1 (Dlk1/Pref-1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a Special Issue entitled: Stem Cells and Bone....

  2. Skeletal surveys in multiple myeloma

    International Nuclear Information System (INIS)

    Thirty-three patients with multiple myeloma were studied with serial skeletal surveys, serum immunoglobulin levels, and postabsorptive urinary hydroxyproline (Spot-HYPRO) determinations. Twenty receiving chemotherapy were also followed with skeletal surveys in order to evaluate bone response to treatment. A close association was found between skeletal findings and changes in immunoglubulin levels with positive correlation in 71% of the patients. A similar association was found between skeletal disease and Spot-HYPRO level changes in 65%. Five of 12 patients (42%) with partial or complete clinical response to chemotherapy, demonstrated improvement in the appearance of skeletal lesions. Positive correlation between the roentgenographic changes and clinical markers of myeloma as well as therapeutic response, indicates that skeletal surveys are useful and effective in monitoring patients with multiple myeloma. (orig.)

  3. Segregation of male-sterility alleles across a species boundary.

    Science.gov (United States)

    Weller, S G; Sakai, A K; Culley, T M; Duong, L; Danielson, R E

    2014-02-01

    Hybrid zones may serve as bridges permitting gene flow between species, including alleles influencing the evolution of breeding systems. Using greenhouse crosses, we assessed the likelihood that a hybrid zone could serve as a conduit for transfer of nuclear male-sterility alleles between a gynodioecious species and a hermaphroditic species with very rare females in some populations. Segregation patterns in progeny of crosses between rare females of hermaphroditic Schiedea menziesii and hermaphroditic plants of gynodioecious Schiedea salicaria heterozygous at the male-sterility locus, and between female S. salicaria and hermaphroditic plants from the hybrid zone, were used to determine whether male-sterility was controlled at the same locus in the parental species and the hybrid zone. Segregations of females and hermaphrodites in approximately equal ratios from many of the crosses indicate that the same nuclear male-sterility allele occurs in the parent species and the hybrid zone. These rare male-sterility alleles in S. menziesii may result from gene flow from S. salicaria through the hybrid zone, presumably facilitated by wind pollination in S. salicaria. Alternatively, rare male-sterility alleles might result from a reversal from gynodioecy to hermaphroditism in S. menziesii, or possibly de novo evolution of male sterility. Phylogenetic analysis indicates that some species of Schiedea have probably evolved separate sexes independently, but not in the lineage containing S. salicaria and S. menziesii. High levels of selfing and expression of strong inbreeding depression in S. menziesii, which together should favour females in populations, argue against a reversal from gynodioecy to hermaphroditism in S. menziesii.

  4. Angiotensin-converting enzyme genotype affects skeletal muscle strength in elite athletes.

    Science.gov (United States)

    Costa, Aldo Matos; Silva, António José; Garrido, Nuno; Louro, Hugo; Marinho, Daniel Almeida; Cardoso Marques, Mário; Breitenfeld, Luiza

    2009-01-01

    Previous studies have associated angiotensin-converting enzyme (ACE) D allele with variability in the skeletal muscle baseline strength, though conclusions have been inconsistent across investigations. The purpose of this study was to examine the possible association between ACE genotype and skeletal muscle baseline strength in elite male and female athletes involved in different event expertise. A group of 58 elite athletes, designated as Olympic candidates, were studied: 35 swimmers (19 males and 16 females, 18.8 ± 3.2 years) and 23 triathletes (15 males and 8 females, 18.7 ± 3.0 years). The athletes were classified as: short (≤ 200m) and middle (400m to 1500m) distance athletes, respectively. For each subject the grip strength in both hands was measure using an adjustable mechanical hand dynamometer. The maximum height in both squat jump (SJ) and counter movement jump (CMJ) were also assessed, using a trigonometric carpet (Ergojump Digitime 1000; Digitest, Jyvaskyla, Finland). DNA extraction was obtained with Chelex 100(®) and genotype determination by PCR-RFLP methods. Both males and females showed significantly higher right grip strength in D allele carriers compared to II homozygote's. We found that allelic frequency differs significantly by event distance specialization in both genders (p sprinter D allele carriers showed the superior scores in nearly all strength measurements (p < 0.05), in both genders. Among endurance athletes, the results also demonstrated that female D allele carriers exhibited the higher performance right grip and CMJ scores (p < 0.05). In conclusion, the ACE D allele seems associated with skeletal muscle baseline strength in elite athletes, being easily identified in females. Key pointsDD homozygote's and D allele carriers from both genders shows significantly higher right grip strength.Right grip strength remains significantly higher in the D allele carrier's female endurance group.Female's D allele carriers exhibited the higher

  5. Skeletal Effects of Smoking.

    Science.gov (United States)

    Cusano, Natalie E

    2015-10-01

    Smoking is a leading cause of preventable death and disability. Smoking has long been identified as a risk factor for osteoporosis, with data showing that older smokers have decreased bone mineral density and increased fracture risk compared to nonsmokers, particularly at the hip. The increase in fracture risk in smokers is out of proportion to the effects on bone density, indicating deficits in bone quality. Advanced imaging techniques have demonstrated microarchitectural deterioration in smokers, particularly in the trabecular compartment. The mechanisms by which smoking affects skeletal health remain unclear, although multiple pathways have been proposed. Smoking cessation may at least partially reverse the adverse effects of smoking on the skeleton.

  6. Skeletal Effects of Smoking.

    Science.gov (United States)

    Cusano, Natalie E

    2015-10-01

    Smoking is a leading cause of preventable death and disability. Smoking has long been identified as a risk factor for osteoporosis, with data showing that older smokers have decreased bone mineral density and increased fracture risk compared to nonsmokers, particularly at the hip. The increase in fracture risk in smokers is out of proportion to the effects on bone density, indicating deficits in bone quality. Advanced imaging techniques have demonstrated microarchitectural deterioration in smokers, particularly in the trabecular compartment. The mechanisms by which smoking affects skeletal health remain unclear, although multiple pathways have been proposed. Smoking cessation may at least partially reverse the adverse effects of smoking on the skeleton. PMID:26205852

  7. The skeletal system

    International Nuclear Information System (INIS)

    The joy of diagnostic radiology is derived in great measure in its neverending variety including the unveiling of new diagnostic entities and new information concerning known disease processes. This year is no exception in the fascinating documentation of skeletal disease. In the study of disorders of the joints, CT investigation of the temporomandibular joint and arthotomography of the shoulder are gaining in popularity. New observations concerning cyst-like osseous lesions in lupus erthematosis, destructive joint lesions in renal osteodystrophy, and intra- and periarticular calcifications secondary to steroid injections have come forward. Articles discussing interesting observations concerning chondrosarcoma are included as well as one that describes the demonstration of fluid levels in aneurysmal bone cysts by CT. Ossification in soft tissues following resection of giant cell tumors as evidence of residual neoplasm is an important new sign. Marrow transplantation for treatment of mucopolysaccharidosis represents a new therapeutic breakthrough. Some of the skeletal manifestions of hypomagnesemia, 13-cis-retinoic acid, and aluminum are elucidated in this year's articles on metabolic disease. Further studies of methods of measuring bone density are also included

  8. ANGIOTENSIN-CONVERTING ENZYME GENOTYPE AFFECTS SKELETAL MUSCLE STRENGTH IN ELITE ATHLETES

    Directory of Open Access Journals (Sweden)

    Aldo Matos Costa

    2009-09-01

    Full Text Available Previous studies have associated angiotensin-converting enzyme (ACE D allele with variability in the skeletal muscle baseline strength, though conclusions have been inconsistent across investigations. The purpose of this study was to examine the possible association between ACE genotype and skeletal muscle baseline strength in elite male and female athletes involved in different event expertise. A group of 58 elite athletes, designated as Olympic candidates, were studied: 35 swimmers (19 males and 16 females, 18.8 ± 3.2 years and 23 triathletes (15 males and 8 females, 18.7 ± 3.0 years. The athletes were classified as: short (< 200m and middle (400m to 1500m distance athletes, respectively. For each subject the grip strength in both hands was measure using an adjustable mechanical hand dynamometer. The maximum height in both squat jump (SJ and counter movement jump (CMJ were also assessed, using a trigonometric carpet (Ergojump Digitime 1000; Digitest, Jyvaskyla, Finland. DNA extraction was obtained with Chelex 100® and genotype determination by PCR-RFLP methods. Both males and females showed significantly higher right grip strength in D allele carriers compared to II homozygote's. We found that allelic frequency differs significantly by event distance specialization in both genders (p < 0.05. In fact, sprinter D allele carriers showed the superior scores in nearly all strength measurements (p < 0.05, in both genders. Among endurance athletes, the results also demonstrated that female D allele carriers exhibited the higher performance right grip and CMJ scores (p < 0.05. In conclusion, the ACE D allele seems associated with skeletal muscle baseline strength in elite athletes, being easily identified in females

  9. ACTN3 allele frequency in humans covaries with global latitudinal gradient.

    Directory of Open Access Journals (Sweden)

    Scott M Friedlander

    Full Text Available A premature stop codon in ACTN3 resulting in α-actinin-3 deficiency (the ACTN3 577XX genotype is common in humans and reduces strength, muscle mass, and fast-twitch fiber diameter, but increases the metabolic efficiency of skeletal muscle. Linkage disequilibrium data suggest that the ACTN3 R577X allele has undergone positive selection during human evolution. The allele has been hypothesized to be adaptive in environments with scarce resources where efficient muscle metabolism would be selected. Here we test this hypothesis by using recently developed comparative methods that account for evolutionary relatedness and gene flow among populations. We find evidence that the ACTN3 577XX genotype evolved in association with the global latitudinal gradient. Our results suggest that environmental variables related to latitudinal variation, such as species richness and mean annual temperature, may have influenced the adaptive evolution of ACTN3 577XX during recent human history.

  10. Non-Invasive Prenatal Diagnosis of Lethal Skeletal Dysplasia by Targeted Capture Sequencing of Maternal Plasma

    Science.gov (United States)

    Wang, Yaoshen; Chen, Chao; Gao, Changxin; Yu, Song; Liu, Yan; Song, Wei; Asan; Zhu, Hongmei; Yang, Ling; Deng, Hongmei; Su, Yue; Yi, Xin

    2016-01-01

    Background Since the discovery of cell-free foetal DNA in the plasma of pregnant women, many non-invasive prenatal testing assays have been developed. In the area of skeletal dysplasia diagnosis, some PCR-based non-invasive prenatal testing assays have been developed to facilitate the ultrasound diagnosis of skeletal dysplasias that are caused by de novo mutations. However, skeletal dysplasias are a group of heterogeneous genetic diseases, the PCR-based method is hard to detect multiple gene or loci simultaneously, and the diagnosis rate is highly dependent on the accuracy of the ultrasound diagnosis. In this study, we investigated the feasibility of using targeted capture sequencing to detect foetal de novo pathogenic mutations responsible for skeletal dysplasia. Methodology/Principal Findings Three families whose foetuses were affected by skeletal dysplasia and two control families whose foetuses were affected by other single gene diseases were included in this study. Sixteen genes related to some common lethal skeletal dysplasias were selected for analysis, and probes were designed to capture the coding regions of these genes. Targeted capture sequencing was performed on the maternal plasma DNA, the maternal genomic DNA, and the paternal genomic DNA. The de novo pathogenic variants in the plasma DNA data were identified using a bioinformatical process developed for low frequency mutation detection and a strict variant interpretation strategy. The causal variants could be specifically identified in the plasma, and the results were identical to those obtained by sequencing amniotic fluid samples. Furthermore, a mean of 97% foetal specific alleles, which are alleles that are not shared by maternal genomic DNA and amniotic fluid DNA, were identified successfully in plasma samples. Conclusions/Significance Our study shows that capture sequencing of maternal plasma DNA can be used to non-invasive detection of de novo pathogenic variants. This method has the potential

  11. Axial skeletal CT densitometry

    International Nuclear Information System (INIS)

    Since the discovery of the Roentgen ray a precise and accurate assessment of bone mineral content has been a challenge to many investigators. A number of methods have been developed but no one satisfied. Considering its technical possibilities computed tomography is very promising in determination of bone mineral content (BMC). The new modality enables BMC estimations in the axial skeletal trabecular bone. CT densitometry can be performed on a normal commercially available third generation whole body CT scanner. No dedicated device in a special clinical set-up is necessary. In this study 106 patients, most of them clinically suspected of osteoporosis, were examined. The new method CT densitometry has been evaluated. The results have been correlated to alternative BMC determination methods. (Auth.)

  12. Pediatric aspects of skeletal dysplasia.

    Science.gov (United States)

    Ozono, Keiichi; Namba, Noriyuki; Kubota, Takuo; Kitaoka, Taichi; Miura, Kohji; Ohata, Yasuhisa; Fujiwara, Makoto; Miyoshi, Yoko; Michigami, Toshimi

    2012-10-01

    Skeletal dysplasia is a disorder of skeletal development characterized by abnormality in shape, length, a number and mineral density of the bone. Skeletal dysplasia is often associated with manifestation of other organs such as lung, brain and sensory systems. Skeletal dysplasias or dysostosis are classified with more than 400 different names. Enchondral bone formation is a coordinated event of chondrocyte proliferation, differentiation and exchange of terminally maturated chondrocyte with bone. Impaired enchondral bone formation will lead to skeletal dysplasia, especially associated with short long bones. Appropriate bone volume and mineral density are achieved by balance of bone formation and bone resorption and mineralization. The gene encoding fibroblast growth factor receptor 3 is responsible for achondroplasia, representative skeletal dysplasia with short stature. The treatment with growth hormone is approved for achondroplasia in Japan. Osteogenesis imperfecta is characterized by low bone mineral density and fragile bone. Data on the beneficial effect of bisphosphonate for osteogenesis imperfecta are accumulating. Osteopetrosis has high bone mineral density, but sometimes show bone fragility. In Japan as well as other countries, pediatrician treat larger numbers of patients with skeletal dysplasia with short stature and fragile bones compared to 20 years ago.

  13. An atlas of normal skeletal scintigraphy

    International Nuclear Information System (INIS)

    This atlas was compiled to provide the neophyte as well as the experienced radiologist and the nuclear medicine physician with a reference on normal skeletal scintigraphy as an aid in distinguishing normal variations in skeletal uptake from abnormal findings. Each skeletal scintigraph is labeled, and utilizing an identical scale, a relevant skeletal photograph and radiograph are placed adjacent to the scintigraph

  14. Allele Workbench: transcriptome pipeline and interactive graphics for allele-specific expression.

    Directory of Open Access Journals (Sweden)

    Carol A Soderlund

    Full Text Available Sequencing the transcriptome can answer various questions such as determining the transcripts expressed in a given species for a specific tissue or condition, evaluating differential expression, discovering variants, and evaluating allele-specific expression. Differential expression evaluates the expression differences between different strains, tissues, and conditions. Allele-specific expression evaluates expression differences between parental alleles. Both differential expression and allele-specific expression have been studied for heterosis (hybrid vigor, where the hybrid has improved performance over the parents for one or more traits. The Allele Workbench software was developed for a heterosis study that evaluated allele-specific expression for a mouse F1 hybrid using libraries from multiple tissues with biological replicates. This software has been made into a distributable package, which includes a pipeline, a Java interface to build the database, and a Java interface for query and display of the results. The required input is a reference genome, annotation file, and one or more RNA-Seq libraries with optional replicates. It evaluates allelic imbalance at the SNP and transcript level and flags transcripts with significant opposite directional allele-specific expression. The Java interface allows the user to view data from libraries, replicates, genes, transcripts, exons, and variants, including queries on allele imbalance for selected libraries. To determine the impact of allele-specific SNPs on protein folding, variants are annotated with their effect (e.g., missense, and the parental protein sequences may be exported for protein folding analysis. The Allele Workbench processing results in transcript files and read counts that can be used as input to the previously published Transcriptome Computational Workbench, which has a new algorithm for determining a trimmed set of gene ontology terms. The software with demo files is available

  15. Progressive skeletal myopathy, a phenotypic variant of desmin myopathy associated with desmin mutations.

    Science.gov (United States)

    Dalakas, Marinos C; Dagvadorj, Ayush; Goudeau, Bertrand; Park, Kye-Yoon; Takeda, Kazuyo; Simon-Casteras, Monique; Vasconcelos, Olavo; Sambuughin, Nyamkhishig; Shatunov, Alexey; Nagle, James W; Sivakumar, Kumaraswamy; Vicart, Patrick; Goldfarb, Lev G

    2003-03-01

    Desmin myopathy is a familial or sporadic disorder characterized by the presence of desmin mutations that cause skeletal muscle weakness associated with cardiac conduction block, arrhythmia and heart failure. Distinctive histopathologic features include intracytoplasmic accumulation of desmin-reactive deposits and electron-dense granular aggregates in skeletal and cardiac muscle cells. We describe two families with features of adult-onset slowly progressive skeletal myopathy without cardiomyopathy. N342D point mutation was present in the desmin helical rod domain in patients of family 1, and I451M mutation was found in the non-helical tail domain in patients of family 2. Of interest, the same I451M mutation has previously been reported in patients with cardiomyopathy and no signs of skeletal myopathy. Some carriers of the I451M mutation did not develop any disease, suggesting incomplete penetrance. Expression studies demonstrated inability of the N342D mutant desmin to form cellular filamentous network, confirming the pathogenic role of this mutation, but the network was not affected by the tail-domain I451M mutation. Progressive skeletal myopathy is a rare phenotypic variant of desmin myopathy allelic to the more frequent cardio-skeletal form.

  16. Neurology of endemic skeletal fluorosis

    Directory of Open Access Journals (Sweden)

    Reddy D

    2009-01-01

    Full Text Available Endemic skeletal fluorosis is widely prevalent in India and is a major public health problem. The first ever report of endemic skeletal fluorosis and neurological manifestation was from Prakasam district in Andhra Pradesh in the year 1937. Epidemiological and experimental studies in the endemic areas suggest the role of temperate climate, hard physical labor, nutritional status, presence of abnormal concentrations of trace elements like strontium, uranium, silica in water supplies, high fluoride levels in foods and presence of kidney disease in the development of skeletal fluorosis. Neurological complications of endemic skeletal fluorosis, namely radiculopathy, myelopathy or both are mechanical in nature and till date the evidence for direct neurotoxicity of fluoride is lacking. Prevention of the disease should be the aim, knowing the pathogenesis of fluorosis. Surgery has a limited role in alleviating the neurological disability and should be tailored to the individual based on the imaging findings.

  17. Simvastatin effects on skeletal muscle

    DEFF Research Database (Denmark)

    Larsen, Steen; Stride, Nis; Hey-Mogensen, Martin;

    2013-01-01

    Glucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9)....

  18. Aneuploidy and Skeletal Health

    Science.gov (United States)

    Kamalakar, Archana; Harris, John R.; McKelvey, Kent D.; Suva, Larry J.

    2014-01-01

    The normal human chromosome complement consists of 46 chromosomes comprising 22 morphologically different pairs of autosomes and one pair of sex chromosomes. Variations in either chromosome number and/or structure frequently result in significant mental impairment, and/or a variety of other clinical problems, among them, altered bone mass and strength. Chromosomal syndromes associated with specific chromosomal abnormalities are classified as either numerical or structural and may involve more than one chromosome. Aneuploidy refers to the presence of an extra copy of a specific chromosome, or trisomy, as seen in Down’s syndrome (trisomy 21), or the absence of a single chromosome, or monosomy, as seen in Turner syndrome (a single X chromosome in females: 45, X). Aneuploidies have diverse phenotypic consequences, ranging from severe mental retardation and developmental abnormalities to increased susceptibility to various neoplasms and premature death. In fact, trisomy 21 is the prototypical aneuploidy in humans, is the most common genetic abnormality associated with longevity and is one of the most widespread genetic causes of intellectual disability. In this review, the impact of trisomy 21 on the bone mass, architecture, skeletal health and quality of life of people with Down syndrome will be discussed. PMID:24980541

  19. Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

    Energy Technology Data Exchange (ETDEWEB)

    Rosendahl, K.; Maurseth, K.; Olsen, Oe.E. [Dept. of Paediatric Radiology, Haukeland University Hospital, Bergen (Norway); Halvorsen, O.J. [Dept. of Pathology, Haukeland University Hospital, Bergen (Norway); Gjelland, K. [Dept. of Gynaecology, Haukeland University Hospital, Bergen (Norway); Engebretsen, L. [Dept. of Genetics, Haukeland University Hospital, Bergen (Norway)

    2001-09-01

    We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

  20. Evolutionary dynamics of sporophytic self-incompatibility alleles in plants

    DEFF Research Database (Denmark)

    Schierup, M H; Vekemans, X; Christiansen, F B

    1997-01-01

    The stationary frequency distribution and allelic dynamics in finite populations are analyzed through stochastic simulations in three models of single-locus, multi-allelic sporophytic self-incompatibility. The models differ in the dominance relationships among alleles. In one model, alleles act c...

  1. Ultracapacitor separator

    Science.gov (United States)

    Wei, Chang; Jerabek, Elihu Calvin; LeBlanc, Jr., Oliver Harris

    2001-03-06

    An ultracapacitor includes two solid, nonporous current collectors, two porous electrodes separating the collectors, a porous separator between the electrodes and an electrolyte occupying the pores in the electrodes and separator. The electrolyte is a polar aprotic organic solvent and a salt. The porous separator comprises a wet laid cellulosic material.

  2. Skeletal muscle involvement in cardiomyopathies.

    Science.gov (United States)

    Limongelli, Giuseppe; D'Alessandro, Raffaella; Maddaloni, Valeria; Rea, Alessandra; Sarkozy, Anna; McKenna, William J

    2013-12-01

    The link between heart and skeletal muscle disorders is based on similar molecular, anatomical and clinical features, which are shared by the 'primary' cardiomyopathies and 'primary' neuromuscular disorders. There are, however, some peculiarities that are typical of cardiac and skeletal muscle disorders. Skeletal muscle weakness presenting at any age may indicate a primary neuromuscular disorder (associated with creatine kinase elevation as in dystrophinopathies), a mitochondrial disease (particularly if encephalopathy, ocular myopathy, retinitis, neurosensorineural deafness, lactic acidosis are present), a storage disorder (progressive exercise intolerance, cognitive impairment and retinitis pigmentosa, as in Danon disease), or metabolic disorders (hypoglycaemia, metabolic acidosis, hyperammonaemia or other specific biochemical abnormalities). In such patients, skeletal muscle weakness usually precedes the cardiomyopathy and dominates the clinical picture. Nevertheless, skeletal involvement may be subtle, and the first clinical manifestation of a neuromuscular disorder may be the occurrence of heart failure, conduction disorders or ventricular arrhythmias due to cardiomyopathy. ECG and echocardiogram, and eventually, a more detailed cardiovascular evaluation may be required to identify early cardiac involvement. Paediatric and adult cardiologists should be proactive in screening for neuromuscular and related disorders to enable diagnosis in probands and evaluation of families with a focus on the identification of those at risk of cardiac arrhythmia and emboli who may require specific prophylactic treatments, for example, pacemaker, implantable cardioverter-defibrillator and anticoagulation. PMID:24149064

  3. Quantification of Allele Dosage in tetraploid Roses

    NARCIS (Netherlands)

    Vukosavljev, M.; Guardo, Di M.; Weg, van de W.E.; Arens, P.; Smulders, M.J.M.

    2012-01-01

    Many important crops (wheat, potato, strawberry, rose, etc.) are polyploid. This complicates genetic analyses, as the same locus can be present on multiple homologous or homoeologous chromosomes. SSR markers are suitable for mapping in segregating populations of polyploids as they are multi-allelic,

  4. Diversity of Lactase Persistence Alleles in Ethiopia

    DEFF Research Database (Denmark)

    Jones, BL; Raga, TO; Liebert, Anke;

    2013-01-01

    The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene ...

  5. Diversity of Lactase Persistence Alleles in Ethiopia

    DEFF Research Database (Denmark)

    Jones, BL; Raga, TO; Liebert, Anke;

    2013-01-01

    The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene...

  6. Expression of human PTPN22 alleles

    DEFF Research Database (Denmark)

    Nielsen, C; Barington, T; Husby, S;

    2007-01-01

    Considering the female predominance in most of the autoimmune disorders that associate with the PTPN22 Trp620 variant and the complexity by which this variant influences immunologic tolerance, the objective of this study was to ascertain if the allele-specific expression of the disease-associated...... variant Udgivelsesdato: 2007-Mar...

  7. Cloverleaf skull associated with unusual skeletal anomalies

    International Nuclear Information System (INIS)

    A male infant which cloverleaf skull and multiple other birth defects born to unrelated, healthy, young parents is presented. Radiologic findings in addition to the cloverleaf skull configuration included short, wide clavicles, winged scapulae, unusual shapes of ribs with abnormal spacing between them and with prominent costovertebral junctions, and widely separated ischia. Ulnae appeared angular with probable fusion to the midportion of the radial bones bilaterally. There was polydactyly of the hands and feet with grossly abnormal metacarpal and metatarsal bones. Skeletal maturation was normal. Computed tomography of the skull showed dilated lateral and third ventricles as well as agenesis of the corpus callosum. The mother denies any teratogenic exposure during the pregnancy. The findings in this infant do not seem to fit into any previously described syndrome. (orig.)

  8. Skeletal complications of eating disorders.

    Science.gov (United States)

    Donaldson, Abigail A; Gordon, Catherine M

    2015-09-01

    Anorexia nervosa (AN) is a psychiatric illness with profound medical consequences. Among the many adverse physical sequelae of AN, bone health is impacted by starvation and can be permanently impaired over the course of the illness. In this review of skeletal complications associated with eating disorders, we discuss the epidemiology, neuroendocrine changes, adolescent vs. adult skeletal considerations, orthopedic concerns, assessment of bone health, and treatment options for individuals with AN. The focus of the review is the skeletal sequelae associated with anorexia nervosa, but we also briefly consider other eating disorders that may afflict adolescents and young adults. The review presents updates to the field of bone health in AN, and also suggests knowledge gaps and areas for future investigation. PMID:26166318

  9. Estimating the probability of allelic drop-out of STR alleles in forensic genetics

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Mogensen, Helle Smidt;

    2009-01-01

    In crime cases with available DNA evidence, the amount of DNA is often sparse due to the setting of the crime. In such cases, allelic drop-out of one or more true alleles in STR typing is possible. We present a statistical model for estimating the per locus and overall probability of allelic drop......-out using the results of all STR loci in the case sample as reference. The methodology of logistic regression is appropriate for this analysis, and we demonstrate how to incorporate this in a forensic genetic framework....

  10. Replication study of the vitamin D receptor (VDR) genotype association with skeletal muscle traits and sarcopenia.

    Science.gov (United States)

    Walsh, Sean; Ludlow, Andrew T; Metter, E Jeffrey; Ferrucci, Luigi; Roth, Stephen M

    2016-06-01

    Polymorphisms in the vitamin D receptor (VDR) gene are some of the most studied in relation to skeletal muscle traits and significant associations have been observed by multiple groups. One such paper by our group provided the first evidence of a genetic association with sarcopenia in men, but that finding has yet to be replicated in an independent cohort. In the present study, we examined multiple VDR polymorphisms in relation to skeletal muscle traits and sarcopenia in 864 men and women across the adult age span. In addition to VDR genotypes and haplotypes, measurements of skeletal muscle strength and fat-free mass (FFM) were determined in all subjects and a measure of sarcopenia was calculated. We observed significant associations between Fok1 and Bsm1 genotypes and skeletal muscle strength in men and women, though these associations were modest and no significant associations were observed for these polymorphisms and muscle mass traits nor for Bsm1-Taq1 haplotype with muscle strength. Fok1 FF genotype was associated with an increased the risk of sarcopenia in older women compared to f-allele carriers (1.3-fold higher risk). These results support previous findings that VDR genetic variation appears to impact skeletal muscle strength and risk for sarcopenia but the influence is modest. PMID:26415498

  11. Skeletal stem cells in space and time.

    Science.gov (United States)

    Kassem, Moustapha; Bianco, Paolo

    2015-01-15

    The nature, biological characteristics, and contribution to organ physiology of skeletal stem cells are not completely determined. Chan et al. and Worthley et al. demonstrate that a stem cell for skeletal tissues, and a system of more restricted, downstream progenitors, can be identified in mice and demonstrate its role in skeletal tissue maintenance and regeneration.

  12. Skeletal Muscle Hypertrophy after Aerobic Exercise Training

    OpenAIRE

    Konopka, Adam R.; Harber, Matthew P.

    2014-01-01

    Current dogma suggests aerobic exercise training has minimal effect on skeletal muscle size. We and others have demonstrated that aerobic exercise acutely and chronically alters protein metabolism and induces skeletal muscle hypertrophy. These findings promote an antithesis to the status quo by providing novel perspective on skeletal muscle mass regulation and insight into exercise-countermeasures for populations prone to muscle loss.

  13. Skeletal muscle proteomics: current approaches, technical challenges and emerging techniques

    LENUS (Irish Health Repository)

    Ohlendieck, Kay

    2011-02-01

    Abstract Background Skeletal muscle fibres represent one of the most abundant cell types in mammals. Their highly specialised contractile and metabolic functions depend on a large number of membrane-associated proteins with very high molecular masses, proteins with extensive posttranslational modifications and components that exist in highly complex supramolecular structures. This makes it extremely difficult to perform conventional biochemical studies of potential changes in protein clusters during physiological adaptations or pathological processes. Results Skeletal muscle proteomics attempts to establish the global identification and biochemical characterisation of all members of the muscle-associated protein complement. A considerable number of proteomic studies have employed large-scale separation techniques, such as high-resolution two-dimensional gel electrophoresis or liquid chromatography, and combined them with mass spectrometry as the method of choice for high-throughput protein identification. Muscle proteomics has been applied to the comprehensive biochemical profiling of developing, maturing and aging muscle, as well as the analysis of contractile tissues undergoing physiological adaptations seen in disuse atrophy, physical exercise and chronic muscle transformation. Biomedical investigations into proteome-wide alterations in skeletal muscle tissues were also used to establish novel biomarker signatures of neuromuscular disorders. Importantly, mass spectrometric studies have confirmed the enormous complexity of posttranslational modifications in skeletal muscle proteins. Conclusions This review critically examines the scientific impact of modern muscle proteomics and discusses its successful application for a better understanding of muscle biology, but also outlines its technical limitations and emerging techniques to establish new biomarker candidates.

  14. The acylphosphatase (Acyp) alleles associate with male hybrid sterility in Drosophila.

    Science.gov (United States)

    Michalak, Pawel; Ma, Daina

    2008-06-15

    Hybrid defects are believed to result from genetic incompatibilities between genes that have evolved in separate parental lineages. These genetic dysfunctions on the hybrid genomic background, also known as Dobzhansky-Muller incompatibilities, can be an incipient signature of speciation, and as such - a subject of active research. Here we present evidence that Acyp locus (CG16870) that encodes acylphosphatase, a small enzyme that catalyzes the hydrolysis of acylphosphates and participates in ion transport across biological membranes, is involved in genetic incompatibilities leading to male sterility in hybrids between Drosophila simulans and D. mauritiana. There is a strong association between Acyp alleles (genotype) and the sterility/fertility pattern (phenotype), as well as between the phenotype, the genotype and its transcriptional activity. Allele-specific expression in hybrids heterozygous for Acyp suggests a cis-type regulation of this gene, where an allele from one of the parental species (D. simulans) is consistently overexpressed.

  15. Microsatellite allele frequencies in humans and chimpanzees, with implications for constraints on allele size.

    Science.gov (United States)

    Garza, J C; Slatkin, M; Freimer, N B

    1995-07-01

    The distributions of allele sizes at eight simple-sequence repeat (SSR) or microsatellite loci in chimpanzees are found and compared with the distributions previously obtained from several human populations. At several loci, the differences in average allele size between chimpanzees and humans are sufficiently small that there might be a constraint on the evolution of average allele size. Furthermore, a model that allows for a bias in the mutation process shows that for some loci a weak bias can account for the observations. Several alleles at one of the loci (Mfd 59) were sequenced. Differences between alleles of different lengths were found to be more complex than previously assumed. An 8-base-pair deletion was present in the nonvariable region of the chimpanzee locus. This locus contains a previously unrecognized repeated region, which is imperfect in humans and perfect in chimpanzees. The apparently greater opportunity for mutation conferred by the two perfect repeat regions in chimpanzees is reflected in the higher variance in repeat number at Mfd 59 in chimpanzees than in humans. These data indicate that interspecific differences in allele length are not always attributable to simple changes in the number of repeats. PMID:7659015

  16. Initial invasion of gametophytic self-incompatibility alleles in the absence of tight linkage between pollen and pistil S alleles.

    Science.gov (United States)

    Sakai, Satoki; Wakoh, Haluka

    2014-08-01

    In homomorphic self-incompatibility (SI) systems of plants, the loci controlling the pollen and pistil types are tightly linked, and this prevents the generation of compatible combinations of alleles expressing pollen and pistil types, which would result in self-fertilization. We modeled the initial invasion of the first pollen and pistil alleles in gametophytic SI to determine whether these alleles can stably coexist in a population without tight linkage. We assume pollen and pistil loci each carry an incompatibility allele S and an allele without an incompatibility function N. We assume that pollen with an S allele are incompatible with pistils carrying S alleles, whereas other crosses are compatible. Ovules in pistils carrying an S allele suffer viability costs because recognition consumes resources. We found that the cost of carrying a pistil S allele allows pollen and pistil S alleles to coexist in a stable equilibrium if linkage is partial. This occurs because parents that carry pistil S alleles but are homozygous for pollen N alleles cannot avoid self-fertilization; however, they suffer viability costs. Hence, pollen N alleles are selected again. When pollen and pistil S alleles can coexist in a polymorphic equilibrium, selection will favor tighter linkage.

  17. Choosing a skeletal muscle relaxant.

    Science.gov (United States)

    See, Sharon; Ginzburg, Regina

    2008-08-01

    Skeletal muscle relaxants are widely used in treating musculoskeletal conditions. However, evidence of their effectiveness consists mainly of studies with poor methodologic design. In addition, these drugs have not been proven to be superior to acetaminophen or nonsteroidal anti-inflammatory drugs for low back pain. Systematic reviews and meta-analyses support using skeletal muscle relaxants for short-term relief of acute low back pain when nonsteroidal anti-inflammatory drugs or acetaminophen are not effective or tolerated. Comparison studies have not shown one skeletal muscle relaxant to be superior to another. Cyclobenzaprine is the most heavily studied and has been shown to be effective for various musculoskeletal conditions. The sedative properties of tizanidine and cyclobenzaprine may benefit patients with insomnia caused by severe muscle spasms. Methocarbamol and metaxalone are less sedating, although effectiveness evidence is limited. Adverse effects, particularly dizziness and drowsiness, are consistently reported with all skeletal muscle relaxants. The potential adverse effects should be communicated clearly to the patient. Because of limited comparable effectiveness data, choice of agent should be based on side-effect profile, patient preference, abuse potential, and possible drug interactions. PMID:18711953

  18. Allelic associations of two polymorphic microsatellites in intron 40 of the human von Willebrand factor gene

    Energy Technology Data Exchange (ETDEWEB)

    Pena, S.D.J.; De Souza, K.T. (Nucleo de Genetica Medica de Minas Gerais, Belo Horizonte (Brazil)); De Andrade, M.; Chakraborty, R. (Univ. of Texas Graduate School of Biomedical Sciences, Houston, TX (United States))

    1994-01-18

    At intron 40 of the von Willebrand factor (vWF) gene, two GATA-repeat polymorphic sites exist that are physically separated by 212 bp. At the first site (vWF1 locus), seven segregating repeat alleles were observed in a Brazilian Caucasian population, and at the second (vWF2 locus) there were eight alleles, detected through PCR amplifications of this DNA region. Haplotype analysis of individuals revealed 36 different haplotypes in a sample of 338 chromosomes examined. Allele frequencies between generations and gender at each locus were not significantly different, and the genotype frequencies were consistent with their Hardy-Weinberg expectations. Linkage disequilibrium between loci is highly significant with positive allele size association; that is, large alleles at the loci tend to occur together, and so do the same alleles. Variability at each locus appeared to have arisen in a stepwise fashion, suggesting replication slippage as a possible mechanism of production of new alleles. However, the authors observed an increased number of haplotypes, in contrast with the predictions of a stepwise production of variation in the entire region, suggesting some form of cooperative changes between loci that could be due to either gene conversion, or a common control mechanism of production of new variation at these repeat polymorphism sites. The high degree of polymorphism (gene diversity values of 72% and 78% at vWF1 and vWF2, respectively, and of 93% at the haplotype level) makes these markers informative for paternity testing, genetic counseling, and individual-identification purposes.

  19. Estimation of allele frequencies for VNTR loci.

    OpenAIRE

    Devlin, B; Risch, N; Roeder, K

    1991-01-01

    VNTR loci provide valuable information for a number of fields of study involving human genetics, ranging from forensics (DNA fingerprinting and paternity testing) to linkage analysis and population genetics. Alleles of a VNTR locus are simply fragments obtained from a particular portion of the DNA molecule and are defined in terms of their length. The essential element of a VNTR fragment is the repeat, which is a short sequence of basepairs. The core of the fragment is composed of a variable ...

  20. A Bayesian Approach to Multistage Fitting of the Variation of the Skeletal Age Features

    Directory of Open Access Journals (Sweden)

    Dong Hua

    2009-01-01

    Full Text Available Accurate assessment of skeletal maturity is important clinically. Skeletal age assessment is usually based on features encoded in ossification centers. Therefore, it is critical to design a mechanism to capture as much as possible characteristics of features. We have observed that given a feature, there exist stages of the skeletal age such that the variation pattern of the feature differs in these stages. Based on this observation, we propose a Bayesian cut fitting to describe features in response to the skeletal age. With our approach, appropriate positions for stage separation are determined automatically by a Bayesian approach, and a model is used to fit the variation of a feature within each stage. Our experimental results show that the proposed method surpasses the traditional fitting using only one line or one curve not only in the efficiency and accuracy of fitting but also in global and local feature characterization.

  1. The protease inhibitor PI*S allele and COPD

    DEFF Research Database (Denmark)

    Hersh, C P; Ly, N P; Berkey, C S;

    2005-01-01

    In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear. The current...

  2. Skeletal fluorosis in immobilized extremities.

    Science.gov (United States)

    Rosenquist, J B

    1975-11-01

    The effect of immobilization on skeletal fluorosis was studied in growing rabbits. One hind leg was immobilized by an external fixation device extending below the wrist joint and above the knee joint, the extremity being in a straight position after severance of the sciatic nerve. The animals, aged 7 weeks at the beginning of the experiment, were given 10 mg of fluoride per kg body weight and day during 12 weeks. In the tibiae, development of the skeletal fluorosis was more irregular than that observed in previous studies of normally active animals, being most excessive in the mobile bone. The immobilization effect was most profound in the femora as the cortical thickness and the femur score were significantly higher than those in the mobile femora. It was suggested that an altered muscular activity was the reason for the observed changes. PMID:1189918

  3. Skeletal and body composition evaluation

    Science.gov (United States)

    Mazess, R. B.

    1983-01-01

    Research on radiation detectors for absorptiometry; analysis of errors affective single photon absorptiometry and development of instrumentation; analysis of errors affecting dual photon absorptiometry and development of instrumentation; comparison of skeletal measurements with other techniques; cooperation with NASA projects for skeletal evaluation in spaceflight (Experiment MO-78) and in laboratory studies with immobilized animals; studies of postmenopausal osteoporosis; organization of scientific meetings and workshops on absorptiometric measurement; and development of instrumentation for measurement of fluid shifts in the human body were performed. Instrumentation was developed that allows accurate and precise (2% error) measurements of mineral content in compact and trabecular bone and of the total skeleton. Instrumentation was also developed to measure fluid shifts in the extremities. Radiation exposure with those procedures is low (2-10 MREM). One hundred seventy three technical reports and one hundred and four published papers of studies from the University of Wisconsin Bone Mineral Lab are listed.

  4. Skeletal Fragility in Endogenous Hypercortisolism.

    Science.gov (United States)

    Mazziotti, Gherardo; Delgado, Adriano; Maffezzoni, Filippo; Formenti, Annamaria; Giustina, Andrea

    2016-01-01

    Skeletal fragility is a frequent complication of endogenous hypercortisolism, and fragility fractures may be the first clinical manifestation of the disease. Fractures involve more frequently the vertebrae and may occur in 30-50% of the patients exposed to glucocorticoid excess, in close relationship with severity and duration of hypercortisolism. Although improvement of bone mineral density was reported after resolution of hypercortisolism, there are patients with persistently high fracture risk after the cure of hypercortisolism, and other patients in whom the resolution of hypercortisolism may take a long time, implying a multistep therapeutic approach. Since vertebral fractures tend to occur early during the natural history of disease, a skeletal-specific approach should be undertaken in these patients; however, the cost-effectiveness of this approach is still largely unknown since data on effectiveness and safety of bone-active drugs in endogenous hypercortisolism are scarce. PMID:27210111

  5. Dideoxy single allele-specific PCR - DSASP new method to discrimination allelic

    Directory of Open Access Journals (Sweden)

    Eleonidas Moura Lima

    2015-06-01

    Full Text Available Gastric cancer (GC is a multifactorial disease with a high mortality rate in Brazil and worldwide. This work aimed to evaluate single nucleotide polymorphisms (SNP rs1695, in the Glutathione S-Transferase Pi (GSTP1 gene in GC samples by comparative analysis Specific PCR - ASP and Dideoxy Single Allele-Specific PCR - DSASP methods. The DSASP is the proposed new method for allelic discrimination. This work analyzed 60 GC samples, 26 diffuse and 34 intestinal types. The SNP rs1695 of the GSTP1 gene was significantly associated with GC analyzed by DSASP method (χ2 = 9.7, P 0.05. These results suggest that the SNP rs1695 of the GSTP1 gene was a risk factor associated with gastric carcinogens is and the DSASP method was a new successfully low-cost strategy to study allelic discrimination.

  6. Determination of DQB1 alleles using PCR amplification and allele-specific primers.

    Science.gov (United States)

    Lepage, V; Ivanova, R; Loste, M N; Mallet, C; Douay, C; Naoumova, E; Charron, D

    1995-10-01

    Molecular genotyping of HLA class II genes is commonly carried out using polymerase chain reaction (PCR) in combination with sequence-specific oligotyping (PCR-SSO) or a combination of the PCR and restriction fragment length polymorphism methods (PCR-RFLP). However, the identification of the DQB1 type by PCR-SSO and PCR-RFLP is very time-consuming which is disadvantageous for the typing of cadaveric organ donors. We have developed a DQB1 typing method using PCR in combination with allele-specific amplification (PCR-ASA), which allows the identification of the 17 most frequent alleles in one step using seven amplification mixtures. PCR allele-specific amplification HLA-DQB1 typing is easy to perform, and the results are easy to interpret in routine clinical practice. The PCR-ASA method is therefore better suited to DQB1 typing for organ transplantation than other methods.

  7. Borrowed alleles and convergence in serpentine adaptation.

    Science.gov (United States)

    Arnold, Brian J; Lahner, Brett; DaCosta, Jeffrey M; Weisman, Caroline M; Hollister, Jesse D; Salt, David E; Bomblies, Kirsten; Yant, Levi

    2016-07-19

    Serpentine barrens represent extreme hazards for plant colonists. These sites are characterized by high porosity leading to drought, lack of essential mineral nutrients, and phytotoxic levels of metals. Nevertheless, nature forged populations adapted to these challenges. Here, we use a population-based evolutionary genomic approach coupled with elemental profiling to assess how autotetraploid Arabidopsis arenosa adapted to a multichallenge serpentine habitat in the Austrian Alps. We first demonstrate that serpentine-adapted plants exhibit dramatically altered elemental accumulation levels in common conditions, and then resequence 24 autotetraploid individuals from three populations to perform a genome scan. We find evidence for highly localized selective sweeps that point to a polygenic, multitrait basis for serpentine adaptation. Comparing our results to a previous study of independent serpentine colonizations in the closely related diploid Arabidopsis lyrata in the United Kingdom and United States, we find the highest levels of differentiation in 11 of the same loci, providing candidate alleles for mediating convergent evolution. This overlap between independent colonizations in different species suggests that a limited number of evolutionary strategies are suited to overcome the multiple challenges of serpentine adaptation. Interestingly, we detect footprints of selection in A. arenosa in the context of substantial gene flow from nearby off-serpentine populations of A. arenosa, as well as from A. lyrata In several cases, quantitative tests of introgression indicate that some alleles exhibiting strong selective sweep signatures appear to have been introgressed from A. lyrata This finding suggests that migrant alleles may have facilitated adaptation of A. arenosa to this multihazard environment. PMID:27357660

  8. Skeletal muscle: an endocrine organ.

    Science.gov (United States)

    Pratesi, Alessandra; Tarantini, Francesca; Di Bari, Mauro

    2013-01-01

    Tropism and efficiency of skeletal muscle depend on the complex balance between anabolic and catabolic factors. This balance gradually deteriorates with aging, leading to an age-related decline in muscle quantity and quality, called sarcopenia: this condition plays a central role in physical and functional impairment in late life. The knowledge of the mechanisms that induce sarcopenia and the ability to prevent or counteract them, therefore, can greatly contribute to the prevention of disability and probably also mortality in the elderly. It is well known that skeletal muscle is the target of numerous hormones, but only in recent years studies have shown a role of skeletal muscle as a secretory organ of cytokines and other peptides, denominated myokines (IL6, IL8, IL15, Brain-derived neurotrophic factor, and leukaemia inhibitory factor), which have autocrine, paracrine, or endocrine actions and are deeply involved in inflammatory processes. Physical inactivity promotes an unbalance between these substances towards a pro-inflammatory status, thus favoring the vicious circle of sarcopenia, accumulation of fat - especially visceral - and development of cardiovascular diseases, type 2 diabetes mellitus, cancer, dementia and depression, according to what has been called "the diseasome of physical inactivity". PMID:23858303

  9. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth;

    2014-01-01

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity......-body insulin sensitivity increased by ~24% and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]-Glucose disposal increased by ~30% concomitant with a ~20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake...... the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point towards the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes....

  10. The exercised skeletal muscle: a review

    Directory of Open Access Journals (Sweden)

    Marina Marini

    2010-09-01

    Full Text Available The skeletal muscle is the second more plastic tissue of the body - second to the nervous tissue only. In fact, both physical activity and inactivity contribute to modify the skeletal muscle, by continuous signaling through nerve impulses, mechanical stimuli and humoral clues. In turn, the skeletal muscle sends signals to the body, thus contributing to its homeostasis. We'll review here the contribute of physical exercise to the shaping of skeletal muscle, to the adaptation of its mass and function to the different needs imposed by different physical activities and to the attainment of the health benefits associated with active skeletal muscles. Focus will primarily be on the molecular pathways and on gene regulation that result in skeletal muscle adaptation to exercise.

  11. Myogenin regulates exercise capacity and skeletal muscle metabolism in the adult mouse.

    Directory of Open Access Journals (Sweden)

    Jesse M Flynn

    Full Text Available Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle.

  12. CENTRIFUGAL SEPARATORS

    Science.gov (United States)

    Skarstrom, C.

    1959-03-10

    A centrifugal separator is described for separating gaseous mixtures where the temperature gradients both longitudinally and radially of the centrifuge may be controlled effectively to produce a maximum separation of the process gases flowing through. Tbe invention provides for the balancing of increases and decreases in temperature in various zones of the centrifuge chamber as the result of compression and expansions respectively, of process gases and may be employed effectively both to neutralize harmful temperature gradients and to utilize beneficial temperaturc gradients within the centrifuge.

  13. Advances and challenges in skeletal muscle angiogenesis

    DEFF Research Database (Denmark)

    Olfert, I Mark; Baum, Oliver; Hellsten, Ylva;

    2016-01-01

    during health, but poorly controlled in disease - resulting in either excessive capillary growth (pathological angiogenesis) or losses in capillarity (rarefaction). Given that skeletal muscle comprises nearly 40% of body mass in humans, skeletal muscle capillary density has a significant impact...... on 1) the methodological concerns that have arisen in determining skeletal muscle capillarity, and 2) highlight the concepts that are reshaping our understanding of the angio-adaptation process. We also summarize selected new findings (physical influences, molecular changes and ultrastructural...

  14. Cerebellar medulloblastoma presenting with skeletal metastasis

    OpenAIRE

    Barai Sukanta; Bandopadhayaya G; Julka P; Dhanapathi H; Haloi A; Seith A

    2004-01-01

    Medulloblastomas are highly malignant brain tumours, but only rarely produce skeletal metastases. No case of medulloblastoma has been documented to have produced skeletal metastases prior to craniotomy or shunt surgery. A 21-year-old male presented with pain in the hip and lower back with difficulty in walking of 3 months′ duration. Signs of cerebellar dysfunction were present hence a diagnosis of cerebellar neoplasm or skeletal tuberculosis with cerebellar abscess formation was consid...

  15. Nutrient and energy sensing in skeletal muscle

    OpenAIRE

    Deshmukh, Atul S.

    2009-01-01

    Nutrient overload and physical inactivity often leads to the development of obesity and type 2 diabetes. Acute over-nutrition can induce insulin resistance, while physical exercise enhances skeletal muscle insulin sensitivity. Like every living cell, skeletal muscle senses nutrient and energy signals and to adjust metabolic flux. This thesis focuses on some of the key nutrient and energy sensing (exercise/contraction-induced) pathways in skeletal muscle that regulate metabol...

  16. The Effects of Lactate on Skeletal Muscle

    OpenAIRE

    Willkomm, Lena

    2014-01-01

    Regular exercise and physical activity are cornerstones in the prevention and treatment of numerous chronic conditions, such as type 2 diabetes, coronary heart disease, and age-related sarcopenia. The associated health benefits arise from a number of tissues but due to its high plasticity skeletal muscle plays a pivotal role. The resident stem cells of skeletal muscle tissue, so called Satellite cells (SCs), contribute significantly to skeletal muscle adaptation and hence, maintenance of heal...

  17. DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status

    DEFF Research Database (Denmark)

    Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek;

    2012-01-01

    The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression in per...

  18. Separations chemistry

    International Nuclear Information System (INIS)

    Results of studies on the photochemistry of aqueous Pu solutions and the stability of iodine in liquid and gaseous CO2 are reported. Progress is reported in studies on: the preparation of macroporous bodies filled with oxides and sulfides to be used as adsorbents; the beneficiation of photographic wastes; the anion exchange adsorption of transition elements from thiosulfate solutions; advanced filtration applications of energy significance; high-resolution separations; and, the examination of the separation agents, octylphenylphosphoric acid (OPPA) and trihexyl phosphate (THP)

  19. Product separator

    Science.gov (United States)

    Welsh, Robert A.; Deurbrouck, Albert W.

    1976-01-20

    A secondary light sensitive photoelectric product separator for use with a primary product separator that concentrates a material so that it is visually distinguishable from adjacent materials. The concentrate separation is accomplished first by feeding the material onto a vibratory inclined surface with a liquid flow, such as a wet concentrating table. Vibrations generally perpendicular to the stream direction of flow cause the concentrate to separate from its mixture according to its color. When the concentrate and its surrounding stream reach the recovery end of the table, a detecting device notes the line of color demarcation and triggers a signal if it differs from a normal condition. If no difference is noted nothing moves on the second separator. However, if a difference is detected in the constant monitoring of the color line's location, a product splitter and recovery unit normally positioned near the color line at the recovery end, moves to a new position. In this manner the selected separated concentrate is recovered at a maximum rate regardless of variations in the flow stream or other conditions present.

  20. A Wisp3 Cre-knockin allele produces efficient recombination in spermatocytes during early prophase of meiosis I.

    Directory of Open Access Journals (Sweden)

    Steven Hann

    Full Text Available Individuals with the autosomal recessive skeletal disorder Progressive Pseudorheumatoid Dysplasia have loss-of-function mutations in WISP3, and aberrant WISP3 expression has been detected in tumors from patients with colon and breast cancer. In mice however, neither absence nor over-expression of WISP3 was found to cause a phenotype, and endogenous Wisp3 expression has been difficult to detect. To confirm that Wisp3 knockout mice have no phenotype and to identify potential sites of endogenous Wisp3 expression, we generated mice with a knockin allele (Wisp3 (GFP-Cre designed to express Green Fluorescent Protein (GFP and Cre-recombinase instead of WISP3. Heterozygous and homozygous knockin mice were fertile and indistinguishable from their wild-type littermates, confirming that mice lacking Wisp3 have no phenotype. We could not detect GFP-expression from the knockin allele, but we could detect Cre-expression after crossing mice with the knockin allele to Cre-reporter mice; the double heterozygous offspring had evidence of Cre-mediated recombination in several tissues. The only tissue that had high levels of Cre-mediated recombination was the testis, where recombination in spermatocytes occurred by early prophase of meiosis I. As a consequence, males that were double heterozygous for a Wisp3 (GFP-Cre and a floxed allele only contributed a recombined allele to their offspring. We detected no evidence of Cre-mediated recombination in the female ovary, although when double heterozygous females contributed the reporter allele to their offspring it had recombined ~7% of the time. Wisp3 (GFP-Cre expression therefore occurs less frequently and most likely at a later stage of oocyte development in female mice compared to male mice. We conclude that although WISP3 is dispensable in mice, male mice with a Wisp3 (GFP-Cre allele (Jackson Laboratory stock # 017685 will be useful for studying early prophase of meiosis I and for efficiently recombining floxed

  1. Prevalence of human leukocyte antigen (HLA) DRB1 alleles in Kuwaiti children with juvenile rheumatoid arthritis.

    Science.gov (United States)

    Alsaeid, Khaled; Haider, M Z; Kamal, H; Srivastva, B S; Ayoub, E M

    2002-02-01

    The prevalence of human leukocyte antigen (HLA) DR alleles has been determined in 69 Kuwaiti Arab children with juvenile rheumatoid arthritis (JRA) and compared to that in 212 ethnically matched normal healthy controls using a PCR-sequence specific primers (PCR-SSP) method. A very high incidence of DR3 was detected in JRA patients compared to the controls (P JRA patients was accounted for mainly by an excess of DRB1*0307 (P JRA were analysed separately; 73% compared to 58% for the whole JRA patient group. The frequency of DR1 was also higher in the JRA group compared to controls (P = 0.019, RR = 3.585). Although the incidence of some alleles was higher in the control group (DR13 and DR7), none reached a statistically significant level. All the patients with iridocyclitis had either a DR1 or DR3 allele, except for one child. The frequency of DRB1*03 was found to be much higher in the polyarticular subtype of Kuwaiti JRA cases compared to the oligoarticular subgroup and the controls. Also, a non-significant increase in the frequency of the DRB1*04, *11 and *15 alleles was detected in the polyarticular subtype of the Kuwaiti JRA cases compared to the controls.

  2. Allelic association studies of genome wide association data can reveal errors in marker position assignments

    Directory of Open Access Journals (Sweden)

    Curtis David

    2007-06-01

    Full Text Available Abstract Background Genome wide association (GWA studies provide the opportunity to develop new kinds of analysis. Analysing pairs of markers from separate regions might lead to the detection of allelic association which might indicate an interaction between nearby genes. Methods 396,591 markers typed in 541 subjects were studied. 7.8*1010 pairs of markers were screened and those showing initial evidence for allelic association were subjected to more thorough investigation along with 10 flanking markers on either side. Results No evidence was detected for interaction. However 6 markers appeared to have an incorrect map position according to NCBI Build 35. One of these was corrected in Build 36 and 2 were dropped. The remaining 3 were left with map positions inconsistent with their allelic association relationships. Discussion Although no interaction effects were detected the method was successful in identifying markers with probably incorrect map positions. Conclusion The study of allelic association can supplement other methods for assigning markers to particular map positions. Analyses of this type may usefully be applied to data from future GWA studies.

  3. Computational radiology in skeletal radiography

    Energy Technology Data Exchange (ETDEWEB)

    Peloschek, Ph.; Nemec, S. [Computational Image Analysis and Radiology Lab (CIR), Department of Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Widhalm, P. [Computational Image Analysis and Radiology Lab (CIR), Department of Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Pattern Recognition and Image Processing Group, Department of Computer Aided Automation, Vienna University of Technology, Wiedner Hauptstrasse 8-10/020, A-1040 Vienna (Austria); Donner, R. [Computational Image Analysis and Radiology Lab (CIR), Department of Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Pattern Recognition and Image Processing Group, Department of Computer Aided Automation, Vienna University of Technology, Wiedner Hauptstrasse 8-10/020, A-1040 Vienna (Austria); Institute for Computer Graphics and Vision, Graz University of Technology, Inffeldgasse 16, A-8010 Graz (Austria); Birngruber, E. [Computational Image Analysis and Radiology Lab (CIR), Department of Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Thodberg, H.H. [Visiana Aps, Sollerodvej 57C, DK-2840 Holte (Denmark); Kainberger, F. [Computational Image Analysis and Radiology Lab (CIR), Department of Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Langs, G. [Computational Image Analysis and Radiology Lab (CIR), Department of Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)], E-mail: georg.langs@meduniwien.ac.at

    2009-11-15

    Recent years have brought rapid developments in computational image analysis in musculo-skeletal radiology. Meanwhile the algorithms have reached a maturity that makes initial clinical use feasible. Applications range from joint space measurement to erosion quantification, and from fracture detection to the assessment of alignment angles. Current results of computational image analysis in radiography are very promising, but some fundamental issues remain to be clarified, among which the definition of the optimal trade off between automatization and operator-dependency, the integration of these tools into clinical work flow and last not least the proof of incremental clinical benefit of these methods.

  4. Computational radiology in skeletal radiography

    International Nuclear Information System (INIS)

    Recent years have brought rapid developments in computational image analysis in musculo-skeletal radiology. Meanwhile the algorithms have reached a maturity that makes initial clinical use feasible. Applications range from joint space measurement to erosion quantification, and from fracture detection to the assessment of alignment angles. Current results of computational image analysis in radiography are very promising, but some fundamental issues remain to be clarified, among which the definition of the optimal trade off between automatization and operator-dependency, the integration of these tools into clinical work flow and last not least the proof of incremental clinical benefit of these methods.

  5. SNP GENOTYPING BY TAQMAN ALLELE DISCRIMINATION TECHNIQUE

    Directory of Open Access Journals (Sweden)

    Lucian Negura

    2015-07-01

    Full Text Available Breast cancer is the most frequent neoplasm in women worldwide and the principal cause of deaths by cancer, the majority being by metastatic disease. About half of breast tumors are hormone dependent, and in post-menopause women the preferred first line treatment uses third generation aromatase inhibitors. Aromatase is encoded by CYP19 gene on 15q21.1, and there is strong evidence that mutations in this gene affect its expression, with directconsequences on cancer phenotype and response to treatment. Several single nucleotide polymorphisms have beenstudied on CYP19A1 transcription variant, notably rs727479, rs10046, rs4646 and rs700518. We implemented a Taqman-based allele discrimination assay for the rapid investigation of the 4 SNPs in CYP19A1. We genotyped 22 metastaticbreast cancer patients by the technique described.

  6. Shaping skeletal growth by modular regulatory elements in the Bmp5 gene.

    Directory of Open Access Journals (Sweden)

    Catherine Guenther

    2008-12-01

    Full Text Available Cartilage and bone are formed into a remarkable range of shapes and sizes that underlie many anatomical adaptations to different lifestyles in vertebrates. Although the morphological blueprints for individual cartilage and bony structures must somehow be encoded in the genome, we currently know little about the detailed genomic mechanisms that direct precise growth patterns for particular bones. We have carried out large-scale enhancer surveys to identify the regulatory architecture controlling developmental expression of the mouse Bmp5 gene, which encodes a secreted signaling molecule required for normal morphology of specific skeletal features. Although Bmp5 is expressed in many skeletal precursors, different enhancers control expression in individual bones. Remarkably, we show here that different enhancers also exist for highly restricted spatial subdomains along the surface of individual skeletal structures, including ribs and nasal cartilages. Transgenic, null, and regulatory mutations confirm that these anatomy-specific sequences are sufficient to trigger local changes in skeletal morphology and are required for establishing normal growth rates on separate bone surfaces. Our findings suggest that individual bones are composite structures whose detailed growth patterns are built from many smaller lineage and gene expression domains. Individual enhancers in BMP genes provide a genomic mechanism for controlling precise growth domains in particular cartilages and bones, making it possible to separately regulate skeletal anatomy at highly specific locations in the body.

  7. Expression of Gla proteins during fish skeletal development

    OpenAIRE

    Gavaia, Paulo J.

    2006-01-01

    Senegal sole skeletal development; Skeletal malformations; Skeletal malformation in mediterranean species; Senegal sole skeletal deformities; Zebra fish as model system: skeletal development; Identification of bone cells / skeletal development; Spatial - temporal pattern of bgp expression; Single cell resolution: localization of bgp mRNA; Single cell resolution: Immunolocalization of Bgp; Single cell resolution: localization of mgp mRNA; Single cell resolution: Immunolocalization of Mgp; An i...

  8. The effect of wild card designations and rare alleles in forensic DNA database searches

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Bright, Jo-Anne; Buckleton, John S;

    2015-01-01

    not correspond to any marker in the allelic ladder or appear above or below the extent of the allelic ladder range are assigned the allele designation R for rare allele. R alleles are position specific with respect to the observed/unambiguous allele. The F and R designations are made when the exact genotype has...

  9. Motor endplate cholinesterase in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Fujii,Masafumi

    1982-08-01

    Full Text Available The activity and properties of cholinesterase (ChE of the motor endplate and its fractions were studied in isolated human skeletal muscle. This preparation was used since the ChE activity of the membrane preparation was localized only in the motor endplate. The endplate ChE was stable in the isolated membrane for 4 weeks at 4 degrees C. The specific activity of the extracted ChE of human muscle membrane was 29.6% higher than that of the original membrane. Studies with specific substrates and ChE inhibitors indicated that most of the ChE of human muscle membrane and its fractions was acetylcholinesterase, and that the minor component was pseudocholinesterase. A Michaelis-Menten constant of 3.82 mM was estimated in the endplate ChE, and 0.88 mM in the extracted ChE of the endplate. The extracted human endplate ChE was separated into three fractions by Sephadex G-200 chromatography, and into two fractions by acrylamide gel electrophoresis.

  10. Skeletal stem cells in space and time

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Bianco, Paolo

    2015-01-01

    The nature, biological characteristics, and contribution to organ physiology of skeletal stem cells are not completely determined. Chan et al. and Worthley et al. demonstrate that a stem cell for skeletal tissues, and a system of more restricted, downstream progenitors, can be identified in mice ...

  11. Early prenatal diagnosis of skeletal anomalies

    NARCIS (Netherlands)

    A. Khalil; E. Pajkrt; L.S. Chitty

    2011-01-01

    Objective To review experience of early prenatal diagnosis of skeletal dysplasias, and to explore diagnostic accuracy and improve management. Methods A retrospective review of fetal medicine unit (FMU) records was performed to identify cases where a skeletal dysplasia was suspected by 14 weeks' gest

  12. Mechanical modeling of skeletal muscle functioning.

    NARCIS (Netherlands)

    Linden, van der Bart Jochem Julius Joost

    1998-01-01

    For movement of body or body segments is combined effort needed of the central nervous system and the muscular-skeletal system. This thesis deals with the mechanical functioning of skeletal muscle. That muscles come in a large variety of geometries, suggest the existence of a relation between muscle

  13. Characterization of rapidly and naturally quenched skeletal iron catalysts for FT synthesis

    Institute of Scientific and Technical Information of China (English)

    YAN Shi-run; QIAO Ming-hua; ZHU Yuan-long; FAN Kang-nian

    2004-01-01

    The slurry phase is a promising system for Fischer-Tropsch (FT) synthesis. Since the liquid medium efficiently removes the heat of reaction so that the steady-state reaction is easily achieved. High catalytic activity is maintained due to removal of waxy products from the catalyst surface by the action of solvent. In addition, CO-rich syngas from coal gasification can be directly used in FT synthesis which may increase the thermal efficiency of the indirect coal liquefaction. One of the important problems to be solved for slurry phase FT is the catalyst attrition and separation from wax residue. Fused iron and Raney iron were found to have high attrition resistance and easy to separate from wax in slurry phase FT synthesis, but their activity is relatively low. Amorphous alloys made by rapid quenching techniques have drawn increasing interest due to their superior mechanical,chemical and magnetic properties compared to the thermodynamically stable crystalline alloys of the same compositions. It is reported that rapidly quenched skeletal Ni catalyst showed higher catalytic activity than Raney Ni in selective hydrogenation of unsaturated organic functional groups.In this paper, Fe50Al50 (by weight) alloys with different quenching rates, rapid quenching (RQ) and natural quenching (NQ) were prepared for FT synthesis. The phase composition of alloys was characterized by XRD. The physical properties, thermal-stability and adsorption properties of skeletal Fe that was prepared by leaching aluminum of the corresponding alloy with aqueous solution of NaOH were also studied by BET, in situ XRD and H2- and CO-TPD. It is found from XRD patterns of the alloys that RQ Fe50Al50 is composed of orthorhombic phase, and NQ Fe50Al50 alloy is mainly composed of monoclinic phase. Meanwhile, diffraction peaks of the RQ alloy are seriously broadened. After leaching aluminum by aqueous solution of NaOH at the same conditions,skeletal Fe from the RQ alloy give the higher specific surface

  14. Defective skeletal mineralization in pediatric CKD.

    Science.gov (United States)

    Wesseling-Perry, Katherine

    2015-04-01

    Although traditional diagnosis and treatment of renal osteodystrophy focused on changes in bone turnover, current data demonstrate that abnormalities in skeletal mineralization are also prevalent in pediatric chronic kidney disease (CKD) and likely contribute to skeletal morbidities that continue to plague this population. It is now clear that alterations in osteocyte biology, manifested by changes in osteocytic protein expression, occur in early CKD before abnormalities in traditional measures of mineral metabolism are apparent and may contribute to defective skeletal mineralization. Current treatment paradigms advocate the use of 1,25(OH)2vitamin D for the control of secondary hyperparathyroidism; however, these agents fail to correct defective skeletal mineralization and may exacerbate already altered osteocyte biology. Further studies are critically needed to identify the initial trigger for abnormalities of skeletal mineralization as well as the potential effects that current therapeutic options may have on osteocyte biology and bone mineralization.

  15. Assessment of mandibular growth by skeletal scintigraphy

    International Nuclear Information System (INIS)

    Accurate assessment of facial skeletal growth remains a major problem in craniomaxillofacial surgery. Current methods include: (1) comparisons of chronologic age with growth histories of the patient and the family, (2) hand-wrist radiographs compared with a standard, and (3) serial cephalometric radiographs. Uptake of technetium-99m methylene diphosphonate into bone is a reflection of current metabolic activity and blood flow. Therefore, scintigraphy with this radiopharmaceutical might serve as a good method of assessing skeletal growth. Thirty-four patients, ranging in age from 15 months to 22 years, who were undergoing skeletal scintigrams for acute pathologic conditions of the extremities, were used to develop standards of uptake based on age and skeletal maturation. The results indicate that skeletal scintigraphy may be useful in evaluation of mandibular growth

  16. Cardiac, Skeletal, and smooth muscle mitochondrial respiration

    DEFF Research Database (Denmark)

    Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I;

    2014-01-01

    Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial function. Therefore, this study examined mitochondrial respiratory rates in the smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscle. Cardiac......, skeletal, and smooth muscle was harvested from a total of 22 subjects (53±6 yrs) and mitochondrial respiration assessed in permeabilized fibers. Complex I+II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac, skeletal, to smooth muscle (54±1; 39±4; 15......±1 pmol•s(-1)•mg (-1), pmitochondrial density, also fell progressively from cardiac, skeletal, to smooth muscle (222±13; 115±2; 48±2 umol•g(-1)•min(-1), p

  17. Identification of Multiple Alleles at the Wx Locus and Development of Single Segment Substitution Lines for the Alleles in Rice

    Institute of Scientific and Technical Information of China (English)

    ZENG Rui-zhen; ZHANG Ze-min; HE Feng-hua; XI Zhang-ying; Akshay TALUKDAR; SHI Jun-qiong; QIN Li-jun; HUANG Chao-feng; ZHANG Gui-quan

    2006-01-01

    The microsatellite markers 484/485 and 484/W2R were used to identify the multiple alleles at the Wx locus in rice germplasm. Fifteen alleles were identified in 278 accessions by using microsatellite class and G-T polymorphism. Among these alleles, (CT)12-G, (CT)15-G, (CT)16-G, (CT)17-G, (CT)18-G and (CT)21-G have not been reported. Seventy-two single-segment substitution lines (SSSLs) carrying different alleles at the Wx locus were developed by using Huajingxian 74 with the (CT)11-G allele as a recipient and 20 accessions containing 12 different alleles at the Wx locus as donors. The estimated length of the substituted segments ranged from 2.2 to 77.3 cM with an average of 17.4 cM.

  18. Inheritance of microsatellite alleles in pedigrees of Latvian barley varieties and related European ancestors.

    Science.gov (United States)

    Sjakste, T G; Rashal, I; Röder, M S

    2003-02-01

    Genetic diversity and inheritance of 65 microsatellite (SSR) loci were studied in a set of 37 barley varieties involved in the pedigrees of seven Latvian barley varieties: Abava, Agra, Balga, Imula, Linga, Priekulu 1 and Stendes. Cluster analysis divided all the varieties into two large groups according to their geographic distribution. Moravian, Swedish and Danish varieties clustered separately from varieties from Norway and Finland. The pattern of subgroups of both European and Latvian varieties was in accordance with their pedigree information. Graphical genotypes of microsatellite alleles of all seven barley chromosomes were determined for all the 37 varieties studied. Parental inheritance and transmission of microsatellite alleles through the generations of the pedigrees were analysed. The results confirmed the importance and informative value of microsatellite markers for genetic studies in barley and their utility for barley breeding and other applications in fundamental and applied barley genetics. PMID:12589555

  19. PPARδ regulates satellite cell proliferation and skeletal muscle regeneration

    Directory of Open Access Journals (Sweden)

    Angione Alison R

    2011-11-01

    Full Text Available Abstract Peroxisome proliferator-activated receptors (PPARs are a class of nuclear receptors that play important roles in development and energy metabolism. Whereas PPARδ has been shown to regulate mitochondrial biosynthesis and slow-muscle fiber types, its function in skeletal muscle progenitors (satellite cells is unknown. Since constitutive mutation of Pparδ leads to embryonic lethality, we sought to address this question by conditional knockout (cKO of Pparδ using Myf5-Cre/Pparδflox/flox alleles to ablate PPARδ in myogenic progenitor cells. Although Pparδ-cKO mice were born normally and initially displayed no difference in body weight, muscle size or muscle composition, they later developed metabolic syndrome, which manifested as increased body weight and reduced response to glucose challenge at age nine months. Pparδ-cKO mice had 40% fewer satellite cells than their wild-type littermates, and these satellite cells exhibited reduced growth kinetics and proliferation in vitro. Furthermore, regeneration of Pparδ-cKO muscles was impaired after cardiotoxin-induced injury. Gene expression analysis showed reduced expression of the Forkhead box class O transcription factor 1 (FoxO1 gene in Pparδ-cKO muscles under both quiescent and regenerating conditions, suggesting that PPARδ acts through FoxO1 in regulating muscle progenitor cells. These results support a function of PPARδ in regulating skeletal muscle metabolism and insulin sensitivity, and they establish a novel role of PPARδ in muscle progenitor cells and postnatal muscle regeneration.

  20. GPS Separator

    CERN Multimedia

    2016-01-01

    Footage of the 70 degree ISOLDE GPS separator magnet MAG70 as well as the switchyard for the Central Mass and GLM (GPS Low Mass) and GHM (GPS High Mass) beamlines in the GPS separator zone. In the GPS20 vacuum sector equipment such as the long GPS scanner 482 / 483 unit, faraday cup FC 490, vacuum valves and wiregrid piston WG210 and WG475 and radiation monitors can also be seen. Also the RILIS laser guidance and trajectory can be seen, the GPS main beamgate switch box and the actual GLM, GHM and Central Beamline beamgates in the beamlines as well as the first electrostatic quadrupoles for the GPS lines. Close up of the GHM deflector plates motor and connections and the inspection glass at the GHM side of the switchyard.

  1. HRS Separator

    CERN Multimedia

    2016-01-01

    Footage of the 90 and 60 degree ISOLDE HRS separator magnets in the HRS separator zone. In the two vacuum sectors HRS20 and HRS30 equipment such as the HRS slits SL240, the HRS faraday cup FC300 and wiregrid WG210 can be spotted. Vacuum valves, turbo pumps, beamlines, quadrupoles, water and compressed air connections, DC and signal cabling can be seen throughout the video. The HRS main and user beamgate in the beamline between MAG90 and MAG60 and its switchboxes as well as all vacuum bellows and flanges are shown. Instrumentation such as the HRS scanner unit 482 / 483, the HRS WG470 wiregrid and slits piston can be seen. The different quadrupoles and supports are shown as well as the RILIS guidance tubes and installation at the magnets and the different radiation monitors.

  2. Component Separations

    OpenAIRE

    Heller, Lior; McNichols, Colton H.; Ramirez, Oscar M.

    2012-01-01

    Component separation is a technique used to provide adequate coverage for midline abdominal wall defects such as a large ventral hernia. This surgical technique is based on subcutaneous lateral dissection, fasciotomy lateral to the rectus abdominis muscle, and dissection on the plane between external and internal oblique muscles with medial advancement of the block that includes the rectus muscle and its fascia. This release allows for medial advancement of the fascia and closure of up to 20-...

  3. Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles.

    Directory of Open Access Journals (Sweden)

    Jaan-Olle Andressoo

    2006-10-01

    Full Text Available Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background. We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models. Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria. We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals. Our data suggest a re-evaluation of the contribution of "null" alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals.

  4. Drop-out probabilities of IrisPlex SNP alleles

    DEFF Research Database (Denmark)

    Andersen, Jeppe Dyrberg; Tvedebrink, Torben; Mogensen, Helle Smidt;

    2013-01-01

    -out of true alleles is possible. As part of the validation of the IrisPlex assay in our ISO17025 accredited, forensic genetic laboratory, we estimated the probability of drop-out of specific SNP alleles using 29 and 30 PCR cycles and 25, 50 and 100 Single Base Extension (SBE) cycles. We observed no drop...

  5. Component separations.

    Science.gov (United States)

    Heller, Lior; McNichols, Colton H; Ramirez, Oscar M

    2012-02-01

    Component separation is a technique used to provide adequate coverage for midline abdominal wall defects such as a large ventral hernia. This surgical technique is based on subcutaneous lateral dissection, fasciotomy lateral to the rectus abdominis muscle, and dissection on the plane between external and internal oblique muscles with medial advancement of the block that includes the rectus muscle and its fascia. This release allows for medial advancement of the fascia and closure of up to 20-cm wide defects in the midline area. Since its original description, components separation technique underwent multiple modifications with the ultimate goal to decrease the morbidity associated with the traditional procedure. The extensive subcutaneous lateral dissection had been associated with ischemia of the midline skin edges, wound dehiscence, infection, and seroma. Although the current trend is to proceed with minimally invasive component separation and to reinforce the fascia with mesh, the basic principles of the techniques as described by Ramirez et al in 1990 have not changed over the years. Surgeons who deal with the management of abdominal wall defects are highly encouraged to include this technique in their collection of treatment options. PMID:23372455

  6. PDH regulation in skeletal muscle

    DEFF Research Database (Denmark)

    Kiilerich, Kristian

    Pyruvate dehydrogenase (PDH) decarboxylates pyruvate into acetyl-CoA and links glycolysis with the Krebs cycle. Because PDH is the only step where carbohydrate-derived substrate can enter the mitochondria and become completely oxidized, PDH activity can potentially determine if glycogen / glucose...... is oxidized completely, or whether pyruvate is converted to lactate. Activity of PDH in the active form (PDHa) is overall determined by the degree of PDH-E1? phosphorylation, where PDH-E1? dephosphorylation activates PDH, while PDH-E1? phosphorylation inactivates PDH. The PDH-E1? phosphorylation state...... in mouse skeletal muscle at rest and in response to fasting and during recovery from exercise. The studies indicate that the content of PDH-E1? in human muscle follows the metabolic profile of the muscle, rather than the myosin heavy chain fiber distribution of the muscle. The larger lactate accumulation...

  7. Human skeletal muscle releases leptin in vivo

    DEFF Research Database (Denmark)

    Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund;

    2012-01-01

    was unaltered. During saline infusion the adipose tissue release averaged 0.8 ± 0.3 ng min(-1) 100g tissue(-1) whereas skeletal muscle release was 0.5 ± 0.1 ng min(-1) 100g tissue(-1). In young healthy humans, skeletal muscle contribution to whole body leptin production could be substantial given the greater...... mass of muscle compared to fat. An understanding of the role that leptin plays in skeletal muscle metabolism may prove important in light of several late-phase trials with recombinant leptin as an anti-obesity drug...

  8. SPECT/CT diagnostics for skeletal infections

    International Nuclear Information System (INIS)

    Skeletal infections are often a diagnostic and clinical challenge. Nuclear imaging modalities used in the diagnostic workup of acute and chronic skeletal infections include three-phase bone scintigraphy and scintigraphy with labelled leucocytes. The introduction of hybrid technologies, such as single photon emission computed tomography/computed tomography (SPECT/CT) has dramatically changed nuclear medical imaging of infections. In general SPECT/CT leads to a considerably more accurate diagnosis than planar or SPECT imaging. Given the integrated acquisition of metabolic, functional and morphological information, SPECT/CT has increased in particular the specificity of three-phase skeletal scanning and scintigraphy with labeled leucocytes. (orig.)

  9. Multifocal skeletal tuberculosis: A case report

    Science.gov (United States)

    ZHANG, LIANG; WANG, JINGCHENG; FENG, XINMIN; TAO, YUPING; YANG, JIANDONG; ZHANG, SHENFEI; CAI, JUN

    2016-01-01

    Tuberculosis (TB) of the musculoskeletal system is a rare clinical condition. Multifocal bone involvement is extremely rare and difficult to recognize. Thus, due to the diverse and atypical clinical manifestations of multifocal skeletal TB, the disease is easy to misdiagnose. In the present study, a rare case of atypical disseminated multifocal skeletal TB was reported, which exhibited uncommon findings in radiological images that were more suggestive of a hematological malignancy or metastatic disease. In conclusion, the diagnosis of this condition by conventional diagnostic methods is challenging. The importance of CT-guided needle biopsy and open biopsy in the diagnosis of skeletal TB was emphasized. PMID:27073438

  10. AllelicImbalance: An R/ bioconductor package for detecting, managing, and visualizing allele expression imbalance data from RNA sequencing

    DEFF Research Database (Denmark)

    Gådin, Jesper R.; van't Hooft, Ferdinand M.; Eriksson, Per;

    2015-01-01

    the possible biases. Results: We present AllelicImblance, a software program that is designed to detect, manage, and visualize allelic imbalances comprehensively. The purpose of this software is to allow users to pose genetic questions in any RNA sequencing experiment quickly, enhancing the general utility...

  11. Magnetic separator

    OpenAIRE

    Křupka, Jiří

    2015-01-01

    Cílem bakalářské práce je návrh konstrukčního řešení magnetického separátoru určeného k separaci drobného průmyslového odpadu. Tato zpráva obsahuje přehled zařízení světových výrobců, která slouží k magnetické separaci ocelového odpadu. Dále pak posouzení variant technických řešení konstrukčních uzlů magnetického separátoru a následný výběr konkrétního řešení. Dle vstupních parametrů jsou vypočteny všechny parametry potřebné ke správnému návrhu stroje. Ve výpočtech jsou zahrnuty i odůvodnění ...

  12. Paternal-specific S-allele transmission in sweet cherry (Prunus avium L.): the potential for sexual selection.

    Science.gov (United States)

    Hedhly, A; Wünsch, A; Kartal, Ö; Herrero, M; Hormaza, J I

    2016-03-01

    Homomorphic self-incompatibility is a well-studied example of a physiological process that is thought to increase population diversity and reduce the expression of inbreeding depression. Whereas theoretical models predict the presence of a large number of S-haplotypes with equal frequencies at equilibrium, unequal allele frequencies have been repeatedly reported and attributed to sampling effects, population structure, demographic perturbation, sheltered deleterious mutations or selection pressure on linked genes. However, it is unclear to what extent unequal segregations are the results of gametophytic or sexual selection. Although these two forces are difficult to disentangle, testing S-alleles in the offspring of controlled crosses provides an opportunity to separate these two phenomena. In this work, segregation and transmission of S-alleles have been characterized in progenies of mixed donors and fully compatible pollinations under field conditions in Prunus avium. Seed set patterns and pollen performance have also been characterized. The results reveal paternal-specific distorted transmission of S-alleles in most of the crosses. Interestingly, S-allele segregation within any given paternal or maternal S-locus was random. Observations on pollen germination, pollen tube growth rate, pollen tube cohort size, seed set dynamics and transmission patterns strongly suggest post-pollination, prezygotic sexual selection, with male-male competition as the most likely mechanism. According to these results, post-pollination sexual selection takes precedence over frequency-dependent selection in explaining unequal S-haplotype frequencies. PMID:26559165

  13. Paternal-specific S-allele transmission in sweet cherry (Prunus avium L.): the potential for sexual selection.

    Science.gov (United States)

    Hedhly, A; Wünsch, A; Kartal, Ö; Herrero, M; Hormaza, J I

    2016-03-01

    Homomorphic self-incompatibility is a well-studied example of a physiological process that is thought to increase population diversity and reduce the expression of inbreeding depression. Whereas theoretical models predict the presence of a large number of S-haplotypes with equal frequencies at equilibrium, unequal allele frequencies have been repeatedly reported and attributed to sampling effects, population structure, demographic perturbation, sheltered deleterious mutations or selection pressure on linked genes. However, it is unclear to what extent unequal segregations are the results of gametophytic or sexual selection. Although these two forces are difficult to disentangle, testing S-alleles in the offspring of controlled crosses provides an opportunity to separate these two phenomena. In this work, segregation and transmission of S-alleles have been characterized in progenies of mixed donors and fully compatible pollinations under field conditions in Prunus avium. Seed set patterns and pollen performance have also been characterized. The results reveal paternal-specific distorted transmission of S-alleles in most of the crosses. Interestingly, S-allele segregation within any given paternal or maternal S-locus was random. Observations on pollen germination, pollen tube growth rate, pollen tube cohort size, seed set dynamics and transmission patterns strongly suggest post-pollination, prezygotic sexual selection, with male-male competition as the most likely mechanism. According to these results, post-pollination sexual selection takes precedence over frequency-dependent selection in explaining unequal S-haplotype frequencies.

  14. Skeletal muscle glucose uptake during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik A.

    2005-01-01

    The increase in skeletal muscle glucose uptake during exercise results from a coordinated increase in rates of glucose delivery (higher capillary perfusion), surface membrane glucose transport, and intracellular substrate flux through glycolysis. The mechanism behind the movement of GLUT4...

  15. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

  16. Inflammation induced loss of skeletal muscle.

    Science.gov (United States)

    Londhe, Priya; Guttridge, Denis C

    2015-11-01

    Inflammation is an important contributor to the pathology of diseases implicated in skeletal muscle dysfunction. A number of diseases and disorders including inflammatory myopathies and Chronic Obstructive Pulmonary Disorder (COPD) are characterized by chronic inflammation or elevation of the inflammatory mediators. While these disease states exhibit different pathologies, all have in common the loss of skeletal muscle mass and a deregulated skeletal muscle physiology. Pro-inflammatory cytokines are key contributors to chronic inflammation found in many of these diseases. This section of the review focuses on some of the known inflammatory disorders like COPD, Rheumatoid Arthritis (RA) and inflammatory myopathies that display skeletal muscle atrophy and also provides the reader an overview of the mediators of inflammation, their signaling pathways, and mechanisms of action. This article is part of a Special Issue entitled "Muscle Bone Interactions".

  17. Exercise Promotes Healthy Aging of Skeletal Muscle

    DEFF Research Database (Denmark)

    Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M;

    2016-01-01

    Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes cau...

  18. Common alleles contribute to schizophrenia in CNV carriers

    Science.gov (United States)

    Tansey, K E; Rees, E; Linden, D E; Ripke, S; Chambert, K D; Moran, J L; McCarroll, S A; Holmans, P; Kirov, G; Walters, J; Owen, M J; O'Donovan, M C

    2016-01-01

    The genetic architecture of schizophrenia is complex, involving risk alleles ranging from common alleles of weak effect to rare alleles of large effect, the best exemplar of the latter being large copy number variants (CNVs). It is currently unknown whether pathophysiology in those with defined rare mutations overlaps with that in other individuals with the disorder who do not share the same rare mutation. Under an extreme heterogeneity model, carriers of specific high-penetrance mutations form distinct subgroups. In contrast, under a polygenic threshold model, high-penetrance rare allele carriers possess many risk factors, of which the rare allele is the only one, albeit an important, factor. Under the latter model, cases with rare mutations can be expected to share some common risk alleles, and therefore pathophysiological mechanisms, with cases without the same mutation. Here we show that, compared with controls, individuals with schizophrenia who have known pathogenic CNVs carry an excess burden of common risk alleles (P=2.25 × 10−17) defined from a genome-wide association study largely based on individuals without known CNVs. Our finding is not consistent with an extreme heterogeneity model for CNV carriers, but does offer support for the polygenic threshold model of schizophrenia. That this is so provides support for the notion that studies aiming to model the effects of rare variation may uncover pathophysiological mechanisms of relevance to those with the disorder more widely. PMID:26390827

  19. [Regeneration capacity of skeletal muscle].

    Science.gov (United States)

    Wernig, A

    2003-07-01

    The organotypic stem cell of skeletal muscle has previously been known as satellite cell. They allow muscle fiber growth during ontogenesis, enable fiber hypertrophy and are responsible for the very efficient repair of muscle fibers. This efficient apparatus is to some degree counterbalanced by an enormous use of the satellite cell pool: fiber atrophy probably is accompanied by loss of myonuclei such that every reversal of atrophy is bound to use new myonuclei i.e. satellite cells. How often in life does this occur? Hard to say. Moreover, the potent repair capacity is challenged by an unexpected vulnerability of skeletal muscle fibers: Passive stretching of contracted muscles may cause multiple "microdamage," disruption of contractile elements or tiny areas of true necrosis (focal necrosis). How often does this happen? Well, for many of us at least once per year when we go up and down mountains during vacation time, followed by sour muscles. Others may decide to change his/her (locomotor) behaviour by severe onset of jogging; it may happen that they suffer kidney failure on Monday due to muscle microdamage and the transfer of myoproteins into the serum over weekend. Also 20 minutes of stepping up and down something like a chair will do: There is a remarkable increase in kreatin kinase and other muscle derived proteins which lasts for days and is bound to reflect some muscle damage. How about sportsmen and worker who repeatedly use their muscles in such a way? We don't have answers yet to most of these questions, but considerable amount of information has been collected over the last years both in animal and--less--in human. What is common in all cases of growth and repair is the proliferation of the satellite cells and their consequent incorporation and fusion with the parent fiber. This way focal damage is repaired often without visible reminders. We would run out of satellite cells were they not stem cells: After division one daughter remains a satellite cell

  20. Increased skeletal muscle capillarization enhances insulin sensitivity.

    Science.gov (United States)

    Akerstrom, Thorbjorn; Laub, Lasse; Vedel, Kenneth; Brand, Christian Lehn; Pedersen, Bente Klarlund; Lindqvist, Anna Kaufmann; Wojtaszewski, Jørgen F P; Hellsten, Ylva

    2014-12-15

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. Therefore, we investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle-specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist prazosin to the drinking water of Sprague-Dawley rats (n = 33), whereas 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-wk prazosin treatment, which ensured that prazosin was cleared from the blood stream. Whole body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue-specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]glucose during the plateau phase of the clamp. Whole body insulin sensitivity increased by ∼24%, and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]glucose disposal increased by ∼30% concomitant with an ∼20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point toward the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes. PMID:25352432

  1. Skeletal Aging and Osteoporosis Biomechanics and Mechanobiology

    CERN Document Server

    2013-01-01

    The focus of this book is on mechanical aspects of skeletal fragility related to aging and osteoporosis. Topics include: Age-related changes in trabecular structure and strength; age-related changes in cortical material properties; age-related changes in whole-bone structure; predicting bone strength and fracture risk using image-based methods and finite element analysis; animal models of osteoporosis and aging; age-related changes in skeletal mechano responsiveness; exercise and physical interventions for osteoporosis.

  2. Multifocal skeletal tuberculosis: A case report

    OpenAIRE

    Zhang, Liang; Wang, Jingcheng; Feng, Xinmin; Tao, Yuping; Yang, Jiandong; ZHANG, SHENFEI; Cai, Jun

    2016-01-01

    Tuberculosis (TB) of the musculoskeletal system is a rare clinical condition. Multifocal bone involvement is extremely rare and difficult to recognize. Thus, due to the diverse and atypical clinical manifestations of multifocal skeletal TB, the disease is easy to misdiagnose. In the present study, a rare case of atypical disseminated multifocal skeletal TB was reported, which exhibited uncommon findings in radiological images that were more suggestive of a hematological malignancy or metastat...

  3. Redox control of skeletal muscle atrophy.

    Science.gov (United States)

    Powers, Scott K; Morton, Aaron B; Ahn, Bumsoo; Smuder, Ashley J

    2016-09-01

    Skeletal muscles comprise the largest organ system in the body and play an essential role in body movement, breathing, and glucose homeostasis. Skeletal muscle is also an important endocrine organ that contributes to the health of numerous body organs. Therefore, maintaining healthy skeletal muscles is important to support overall health of the body. Prolonged periods of muscle inactivity (e.g., bed rest or limb immobilization) or chronic inflammatory diseases (i.e., cancer, kidney failure, etc.) result in skeletal muscle atrophy. An excessive loss of muscle mass is associated with a poor prognosis in several diseases and significant muscle weakness impairs the quality of life. The skeletal muscle atrophy that occurs in response to inflammatory diseases or prolonged inactivity is often associated with both oxidative and nitrosative stress. In this report, we critically review the experimental evidence that provides support for a causative link between oxidants and muscle atrophy. More specifically, this review will debate the sources of oxidant production in skeletal muscle undergoing atrophy as well as provide a detailed discussion on how reactive oxygen species and reactive nitrogen species modulate the signaling pathways that regulate both protein synthesis and protein breakdown. PMID:26912035

  4. Redox control of skeletal muscle atrophy.

    Science.gov (United States)

    Powers, Scott K; Morton, Aaron B; Ahn, Bumsoo; Smuder, Ashley J

    2016-09-01

    Skeletal muscles comprise the largest organ system in the body and play an essential role in body movement, breathing, and glucose homeostasis. Skeletal muscle is also an important endocrine organ that contributes to the health of numerous body organs. Therefore, maintaining healthy skeletal muscles is important to support overall health of the body. Prolonged periods of muscle inactivity (e.g., bed rest or limb immobilization) or chronic inflammatory diseases (i.e., cancer, kidney failure, etc.) result in skeletal muscle atrophy. An excessive loss of muscle mass is associated with a poor prognosis in several diseases and significant muscle weakness impairs the quality of life. The skeletal muscle atrophy that occurs in response to inflammatory diseases or prolonged inactivity is often associated with both oxidative and nitrosative stress. In this report, we critically review the experimental evidence that provides support for a causative link between oxidants and muscle atrophy. More specifically, this review will debate the sources of oxidant production in skeletal muscle undergoing atrophy as well as provide a detailed discussion on how reactive oxygen species and reactive nitrogen species modulate the signaling pathways that regulate both protein synthesis and protein breakdown.

  5. An analysis of the alleged skeletal remains of Carin Goring.

    Directory of Open Access Journals (Sweden)

    Anna Kjellström

    Full Text Available In 1991, treasure hunters found skeletal remains in an area close to the destroyed country residence of former Nazi leader Hermann Göring in northeastern Berlin. The remains, which were believed to belong to Carin Göring, who was buried at the site, were examined to determine whether it was possible to make a positive identification. The anthropological analysis showed that the remains come from an adult woman. The DNA analysis of several bone elements showed female sex, and a reference sample from Carin's son revealed mtDNA sequences identical to the remains. The profile has one nucleotide difference from the Cambridge reference sequence (rCRS, the common variant 263G. A database search resulted in a frequency of this mtDNA sequence of about 10% out of more than 7,000 European haplotypes. The mtDNA sequence found in the ulna, the cranium and the reference sample is, thus, very common among Europeans. Therefore, nuclear DNA analysis was attempted. The remains as well as a sample from Carin's son were successfully analysed for the three nuclear markers TH01, D7S820 and D8S1179. The nuclear DNA analysis of the two samples revealed one shared allele for each of the three markers, supporting a mother and son relationship. This genetic information together with anthropological and historical files provides an additional piece of circumstantial evidence in our efforts to identify the remains of Carin Göring.

  6. Functionally-Impaired HIV-1 Nef Alleles from a Mother-Child Transmission Pair

    OpenAIRE

    Bond, Vincent C; Michael Powell; Greene, Warner C.; Jalal A. Zuberi; Stringer, Harold G.; Romas Geleziunas; Mafhuz Khan; Roth, William W.

    2002-01-01

    Abstract: Unusual HIV-1 nef alleles were isolated from a woman and her vertically infected child. Both patients eventually progressed to develop AIDS. The child died at age 6.5 years, while the mother is currently alive, 13 years since her diagnosis with HIV-1. Predicted amino acid sequences of both mother and child Nefs diverged from the HIV-1 clade B consensus. In particular, they exhibited two separate 5-amino acid deletions bracketing a Cterminal dileucine regulatory motif and Trp-Gly mut...

  7. Comparison of allele frequencies of eight STR loci from Argentinian Amerindian and European populations.

    Science.gov (United States)

    Sala, A; Penacino, G; Corach, D

    1998-10-01

    Eight STR systems (THO1, FABP, VWA, FES/FPS, HPRTB, F13A1, CSF1PO, and D6S366) were investigated in different ethnic groups of Argentina. Allele and genotype frequencies, power of exclusion, and discriminative power were investigated. Hardy-Weinberg expectations were calculated from heterozygosity levels. FST and G tests demonstrated that significant differences exist among the investigated populations for some of the eight STRs markers. The Wichi Indians are clearly separated from the Mapuche and Tehuelche, who in turn are closer to the European population, suggesting non-Amerindian admixture.

  8. Fibrillin levels in a severely affected Marfan syndrome patient with a null allele

    Energy Technology Data Exchange (ETDEWEB)

    Boxer, M.; Withers, A.P.; Al-Ghaban, Z. [Univ. of Wales, Cardiff (United Kingdom)]|[Ninewells Hospital and Medical School, Dundee (United Kingdom)] [and others

    1994-09-01

    Marfan syndrome is an autosomal dominantly inherited connective tissue disorder characterized by defects in the cardiovascular, skeletal and ocular systems. A patient was first examined in 1992 having survived an acute sortic dissection with subsequent composite repair and insertion of a prosthetic aortic valve. Clinical examination revealed arachnodactyly, narrow, high arched palate with dental crowding, an arm span exceeding her height by 10.5 cm, joint laxity and bilateral lens subluxation. Analysis of the family showed affected members in three generations and the fibrillin gene, FBN1, was shown to segregate with the disease when using polymorphic markers including an RsaI polymorphism in the 3{prime}-untranslated region of the gene. Analysis of patient mRNA for this RsaI polymorphism by RT-PCR (reverse transcriptase-PCR) amplification and restriction enzyme digestion of the PCR products showed that the copy of the gene segregating with the disease was not transcribed. No low level expression of this allele was observed despite RT-PCR amplification incorporating radioactively labelled dCTP, thus revealing a null allele phenotype. Western blotting analysis of fibrillin secreted by the patient`s dermal fibroblasts using fibrillin-specific antibodies showed only normal sized fibrillin protein. However, immunohistochemical studies of the patient`s tissue and fibroblasts showed markedly lowered levels in staining of microfibrillar structures compared with age-matched controls. This low level of expression of the protein affected in Marfan syndrome in a patient with such severe clinical manifestations is surprising since current understanding would suggest that this molecular phenotype should lead to a mild clinical disorder.

  9. Allelic exclusion of immunoglobulin genes: models and mechanisms.

    Science.gov (United States)

    Vettermann, Christian; Schlissel, Mark S

    2010-09-01

    The allelic exclusion of immunoglobulin (Ig) genes is one of the most evolutionarily conserved features of the adaptive immune system and underlies the monospecificity of B cells. While much has been learned about how Ig allelic exclusion is established during B-cell development, the relevance of monospecificity to B-cell function remains enigmatic. Here, we review the theoretical models that have been proposed to explain the establishment of Ig allelic exclusion and focus on the molecular mechanisms utilized by developing B cells to ensure the monoallelic expression of Ig kappa and Ig lambda light chain genes. We also discuss the physiological consequences of Ig allelic exclusion and speculate on the importance of monospecificity of B cells for immune recognition.

  10. Molecular cloning of a full-length cDNA for dentatorubral-pallidoluysian atrophy and regional expressions of the expanded alleles in the CNS

    Energy Technology Data Exchange (ETDEWEB)

    Onodera, Osamu; Oyake, Mutsuo; Takano, Hiroki [Niigata Univ. (Japan)] [and others

    1995-11-01

    Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by genetic anticipation and variable combinations of symptoms including myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, and dementia. Recently, we discovered that DRPLA is caused by unstable expansion of a CAG repeat of a gene on the short arm of chromosome 12. We determined the consensus DRPLA cDNA sequence containing the complete coding region for 1,185 amino acids. The CAG repeat, which is expanded in DRPLA, is located 1,462 bp downstream from the putative methionine initiation codon and encodes a poly-glutamine tract. Although poly-serine and proline tracts exist near the CAG repeats, these poly-serine or proline tracts did not show any polymorphisms, which is in strong contrast to the high heterogeneity in the length of the CAG repeat. Northern blot analysis revealed a 4.7-kb transcript that is widely expressed in various tissues including heart, lung, kidney, placenta, skeletal muscle, and brain. Reverse transcription-PCR analysis revealed that the expanded alleles are transcribed to levels comparable to those of normal alleles. These results indicate that there is no difference in transcriptional efficiency between expanded and normal alleles. Furthermore, mRNA from cerebellar hemispheres of DRPLA patients showed smaller sizes of CAG repeats compared with other regions of the brain, which reflects somatic mosaicism of the expanded alleles of the DRPLA gene. 49 refs., 6 figs.

  11. MHC allele frequency distributions under parasite-driven selection: A simulation model

    Directory of Open Access Journals (Sweden)

    Radwan Jacek

    2010-10-01

    Full Text Available Abstract Background The extreme polymorphism that is observed in major histocompatibility complex (MHC genes, which code for proteins involved in recognition of non-self oligopeptides, is thought to result from a pressure exerted by parasites because parasite antigens are more likely to be recognized by MHC heterozygotes (heterozygote advantage and/or by rare MHC alleles (negative frequency-dependent selection. The Ewens-Watterson test (EW is often used to detect selection acting on MHC genes over the recent history of a population. EW is based on the expectation that allele frequencies under balancing selection should be more even than under neutrality. We used computer simulations to investigate whether this expectation holds for selection exerted by parasites on host MHC genes under conditions of heterozygote advantage and negative frequency-dependent selection acting either simultaneously or separately. Results In agreement with simple models of symmetrical overdominance, we found that heterozygote advantage acting alone in populations does, indeed, result in more even allele frequency distributions than expected under neutrality, and this is easily detectable by EW. However, under negative frequency-dependent selection, or under the joint action of negative frequency-dependent selection and heterozygote advantage, distributions of allele frequencies were less predictable: the majority of distributions were indistinguishable from neutral expectations, while the remaining runs resulted in either more even or more skewed distributions than under neutrality. Conclusions Our results indicate that, as long as negative frequency-dependent selection is an important force maintaining MHC variation, the EW test has limited utility in detecting selection acting on these genes.

  12. DRD4 dopamine receptor allelic diversity in various primate species

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, M.; Higley, D. [NIAAA, Rockville, MD (United States); O`Brien, S. [NCI, Frederick, MD (United States)] [and others

    1994-09-01

    The DRD4 dopamine receptor is uniquely characterized by a 48 bp repeating segment within the coding region, located in exon III. Different DRD4 alleles are produced by the presence of additional 48 bp repeats, each of which adds 16 amino acids to the length of the 3rd intracytoplasmic loop of the receptor. The DRD4 receptor is therefore an intriguing candidate gene for behaviors which are influenced by dopamine function. In several human populations, DRD4 alleles with 2-8 and 10 repeats have previously been identified, and the 4 and 7 repeat alleles are the most abundant. We have determined DRD4 genotypes in the following nonhuman primate species: chimpanzee N=2, pygmy chimpanzee N=2, gorilla N=4, siamang N=2, Gelada baboon N=1, gibbon N=1, orangutan (Bornean and Sumatran) N=62, spider monkey N=4, owl monkey N=1, Colobus monkey N=1, Patas monkey N=1, ruffed lemur N=1, rhesus macaque N=8, and vervet monkey N=28. The degree of DRD4 polymorphism and which DRD4 alleles were present both showed considerable variation across primate species. In contrast to the human, rhesus macaque monkeys were monomorphic. The 4 and 7 repeat allels, highly abundant in the human, may not be present in certain other primates. For example, the four spider monkeys we studied showed the 7, 8 and 9 repeat length alleles and the only gibbon we analyzed was homozygous for the 9 repeat allele (thus far not observed in the human). Genotyping of other primate species and sequencing of the individual DRD4 repeat alleles in different species may help us determine the ancestral DRD4 repeat length and identify connections between DRD4 genotype and phenotype.

  13. ALLELIC POLYMORPHISM OF IFNγ GENE IN PATIENTS WITH PULMONARY TUBERCULOSIS

    OpenAIRE

    E. L. Nikulina; I. O. Naslednikova; Urazova, O. I.; O. V. Voronkova; V. V. Novitsky; E. V. Nekrasov; O. V. Filiniuk; E. G. Churina; K. O. Mikheyeva; R. R. Hasanova; V. A. Serebryakova; N. A. Sukhalentseva

    2014-01-01

    In present work, some immunogenetic aspects of pulmonary tuberculosis were studied, using modern techniques from molecular genetics and immunology. It is shown that carriage of Т allele and homozygous TT genotype in +874А/Т IFNγ gene polymorphism comprise a immunogenetic factor which correlated with a protective effect, regarding a susceptibility to pulmonary tuberculosis. Predisposition for tuberculosis infection is associated with A allele of this gene, as well as with АА and АТ genotypes o...

  14. Apolipoprotein E Alleles, Dyslipidemia,and Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To describe the association between apolipoprotein E alleles, dyslipidemia, and coronary heart disease (CHD). Methods Using polymerase chain reaction (PCR) the restriction fragment length polymorphism (RFLP), we studied the apolipoprotein E genotypes in 142 patients with coronary artery disease (CAD) and 131 age-matched healthy subjects, as well as the association between apolipoprotein, plasma lipids, and CHD. Results Compared with the E3 allele, the E4 allele was associated with elevated total cholesterol (TC) values (average increase about 0.32-0.58 mmol/L), low-density lipoprotein cholesterol (LDL-C) values, and apolipoprotein B (APOB). The E2 allele has opposite effects (average decrease about 0.34-0.61 mmol/L at TC). Both in cases and controls, the allelic frequency of E3/3 was highest, reaching 67.8% of whole volume, hemozygote of apo E3 was moderate, and homozygote E4/4 was low, E2/2 and E4/2 were rare. The frequencies of E3/4 and E4/4 were significantly higher in patients with CAD compared with controls (P<0.001).Conclusion Apolipoprotein E alleles are important genetic markers for dyslipidemia and CHD.The carrier of E4 gene was the risk factor of CHD.

  15. Automatic reconstruction of skeletal structures from TLS forest scenes

    Science.gov (United States)

    Schilling, A.; Maas, H.-G.

    2014-05-01

    Detailed information about 3D forest structure is vital in forest science for analyzing the spatio-temporal development of plants as well as precise harvest forecasting in forest industry. Up to now, the majority of methods focus on complete structural reconstruction of trees from multiple scans, which might not be a suitable starting point with respect to modeling forest scenes over larger areas. For this reason, we propose a strategy to obtain skeletal structures of trees from single scans following a divide-and-conquer approach well-known from computer science. First, we split the range image into components representing surface patches and trace each component's boundary, which is essential for our skeleton retrieval method. Therefore, we propose an extension to standard boundary tracing that takes a component's interior depth discontinuities into account. Second, each component is processed separately: A 2D skeleton is obtained via the Voronoi Diagram and refined. Subsequently, a component is segmented into subsets of points depending on their proximity to skeleton nodes. Afterwards, the skeleton is split into paths and a Principal Curve is computed from each path's point cluster in order to retrieve the component shape as a set of 3D polygonal lines. Our method retrieves the intricate branching structure of components representing tree crown parts reliably and efficiently. The results are fitting with respect to a visual inspection. At present, results are fragments of tree skeletons, but it opens an attractive perspective to complete tree skeletons from skeletal parts, which we currently regard as future work.

  16. Skeletal Manifestations of Scurvy: A Case Report from Dubai

    Directory of Open Access Journals (Sweden)

    Shahryar Noordin

    2012-01-01

    Full Text Available Introduction. Nutritional deficiencies are rarely reported in developed countries. We report a child of Pakistani origin brought up in Dubai who developed skeletal manifestations of scurvy due to peculiar dietary habits. Case Presentation. A 4.5 year old boy presented with pain and swelling of multiple joints for three months and inability to walk for two months. Dietary history was significant for exclusive meat intake for the preceding two years. On examination the child’s height and weight were below the 5th percentile for his age. He was pale and tachycardic. There was significant swelling and tenderness over the wrist, knee and ankle joints, along with painful restriction of motion. Basic blood workup was unremarkable except for anemia. However, X-rays showed delayed bone age, severe osteopenia of the long bones, epiphyseal separation, cortical thinning and dense zone of provisional calcification, suggesting a radiological diagnosis of scurvy. The child was started on vitamin C replacement therapy. Over the following two months, the pain and swelling substantially reduced and the child became able to walk. Repeat X-rays showed improvement in the bony abnormalities. Conclusion. Although scurvy is not a very commonly encountered entity in the modern era, inappropriate dietary intake can lead to skeletal abnormalities which may be confused with rickets. A high index of suspicion is thus required for prompt diagnosis of scurvy in patients with bone and joint symptoms.

  17. Skeletal manifestations of scurvy: a case report from dubai.

    Science.gov (United States)

    Noordin, Shahryar; Baloch, Naveed; Salat, Muhammad Sohail; Rashid Memon, Abdul; Ahmad, Tashfeen

    2012-01-01

    Introduction. Nutritional deficiencies are rarely reported in developed countries. We report a child of Pakistani origin brought up in Dubai who developed skeletal manifestations of scurvy due to peculiar dietary habits. Case Presentation. A 4.5 year old boy presented with pain and swelling of multiple joints for three months and inability to walk for two months. Dietary history was significant for exclusive meat intake for the preceding two years. On examination the child's height and weight were below the 5th percentile for his age. He was pale and tachycardic. There was significant swelling and tenderness over the wrist, knee and ankle joints, along with painful restriction of motion. Basic blood workup was unremarkable except for anemia. However, X-rays showed delayed bone age, severe osteopenia of the long bones, epiphyseal separation, cortical thinning and dense zone of provisional calcification, suggesting a radiological diagnosis of scurvy. The child was started on vitamin C replacement therapy. Over the following two months, the pain and swelling substantially reduced and the child became able to walk. Repeat X-rays showed improvement in the bony abnormalities. Conclusion. Although scurvy is not a very commonly encountered entity in the modern era, inappropriate dietary intake can lead to skeletal abnormalities which may be confused with rickets. A high index of suspicion is thus required for prompt diagnosis of scurvy in patients with bone and joint symptoms.

  18. Allelic imbalance analysis by high-density single-nucleotide polymorphic allele (SNP) array with whole genome amplified DNA

    OpenAIRE

    Wong, Kwong-Kwok; Tsang, Yvonne T.M.; Shen, Jianhe; Cheng, Rita S.; Chang, Yi-Mieng; Man, Tsz-Kwong; Lau, Ching C.

    2004-01-01

    Besides their use in mRNA expression profiling, oligonucleotide microarrays have also been applied to single-nucleotide polymorphism (SNP) and loss of heterozygosity (LOH) or allelic imbalance studies. In this report, we evaluate the reliability of using whole genome amplified DNA for analysis with an oligonucleotide microarray containing 11 560 SNPs to detect allelic imbalance and chromosomal copy number abnormalities. Whole genome SNP analyses were performed with DNA extracted from osteosar...

  19. How sex hormones promote skeletal muscle regeneration.

    Science.gov (United States)

    Velders, Martina; Diel, Patrick

    2013-11-01

    Skeletal muscle regeneration efficiency declines with age for both men and women. This decline impacts on functional capabilities in the elderly and limits their ability to engage in regular physical activity and to maintain independence. Aging is associated with a decline in sex hormone production. Therefore, elucidating the effects of sex hormone substitution on skeletal muscle homeostasis and regeneration after injury or disuse is highly relevant for the aging population, where sarcopenia affects more than 30 % of individuals over 60 years of age. While the anabolic effects of androgens are well known, the effects of estrogens on skeletal muscle anabolism have only been uncovered in recent times. Hence, the purpose of this review is to provide a mechanistic insight into the regulation of skeletal muscle regenerative processes by both androgens and estrogens. Animal studies using estrogen receptor (ER) antagonists and receptor subtype selective agonists have revealed that estrogens act through both genomic and non-genomic pathways to reduce leukocyte invasion and increase satellite cell numbers in regenerating skeletal muscle tissue. Although animal studies have been more conclusive than human studies in establishing a role for sex hormones in the attenuation of muscle damage, data from a number of recent well controlled human studies is presented to support the notion that hormonal therapies and exercise induce added positive effects on functional measures and lean tissue mass. Based on the fact that aging human skeletal muscle retains the ability to adapt to exercise with enhanced satellite cell activation, combining sex hormone therapies with exercise may induce additive effects on satellite cell accretion. There is evidence to suggest that there is a 'window of opportunity' after the onset of a hypogonadal state such as menopause, to initiate a hormonal therapy in order to achieve maximal benefits for skeletal muscle health. Novel receptor subtype selective

  20. How sex hormones promote skeletal muscle regeneration.

    Science.gov (United States)

    Velders, Martina; Diel, Patrick

    2013-11-01

    Skeletal muscle regeneration efficiency declines with age for both men and women. This decline impacts on functional capabilities in the elderly and limits their ability to engage in regular physical activity and to maintain independence. Aging is associated with a decline in sex hormone production. Therefore, elucidating the effects of sex hormone substitution on skeletal muscle homeostasis and regeneration after injury or disuse is highly relevant for the aging population, where sarcopenia affects more than 30 % of individuals over 60 years of age. While the anabolic effects of androgens are well known, the effects of estrogens on skeletal muscle anabolism have only been uncovered in recent times. Hence, the purpose of this review is to provide a mechanistic insight into the regulation of skeletal muscle regenerative processes by both androgens and estrogens. Animal studies using estrogen receptor (ER) antagonists and receptor subtype selective agonists have revealed that estrogens act through both genomic and non-genomic pathways to reduce leukocyte invasion and increase satellite cell numbers in regenerating skeletal muscle tissue. Although animal studies have been more conclusive than human studies in establishing a role for sex hormones in the attenuation of muscle damage, data from a number of recent well controlled human studies is presented to support the notion that hormonal therapies and exercise induce added positive effects on functional measures and lean tissue mass. Based on the fact that aging human skeletal muscle retains the ability to adapt to exercise with enhanced satellite cell activation, combining sex hormone therapies with exercise may induce additive effects on satellite cell accretion. There is evidence to suggest that there is a 'window of opportunity' after the onset of a hypogonadal state such as menopause, to initiate a hormonal therapy in order to achieve maximal benefits for skeletal muscle health. Novel receptor subtype selective

  1. Influence of skeletal muscle satellite cells implanted into infarcted myocardium on remnant myocyte volumes

    Institute of Scientific and Technical Information of China (English)

    钟竑; 朱洪生; 卫洪超; 张臻

    2003-01-01

    Objective To study the effects of skeletal muscle satellite cells implanted into infarcted myocardium on the volume of remnant myocytes.Methods Thirty-six adult mongrel canines were divided randomly into implantation group and control group. In the implantation group, skeletal muscle satellite cells taken from the gluteus maximus muscles of the dogs were cultured, proliferated and labeled with 4', 6-diamidino-2-phenylindone (DAPI) in vitro. In both groups, a model of acute myocardial infarction was established in every dog. In the implantation group, each dog was injected with M199 solution containing autologous skeletal muscle satellite cells. The dogs in the control group received M199 solution without skeletal muscle satellite cells. The dogs of both groups were killed 2, 4 and 8 weeks after implantation (six dogs in a separate group each time). Both infarcted myocardium and normal myocytes distal from the infracted regions isolated were observed under optical and fluorescent microscope. Their volumes were determined using a confocal microscopy image analysis system and analyzed using SAS. A P<0.05 was considered significant.Results A portion of the implanted cells differentiated into muscle fiber with striations and were connected with intercalated discs. Cross-sectional area and cell volume were increased in normal myocardium. Hypertrophy of remnant myocytes in the infarcted site after skeletal muscle cell implantation was much more evident than in the control group. Cross-sectional area, cell area and cell volume differed significantly from those of the control group (P< 0.05). Hypertrophy of the cells occurred predominantly in terms of width and thickness, whereas cell length remained unchanged. Conclusion Skeletal muscle satellite cells implanted into infarct myocardium, could induce the hypertrophy of remnant myocyte cells in the infarcted site and could also aid in the recovery of the contractile force of the infarcted myocardium.

  2. Lip prints: The barcode of skeletal malocclusion

    Science.gov (United States)

    Raghav, Pradeep; Kumar, Naveen; Shingh, Shishir; Ahuja, N.K.; Ghalaut, Priyanka

    2013-01-01

    Introduction: In orthodontics, apart from essential diagnostic aids, there are so many soft tissue analyses in which lips are major part of concern. However, lip prints have never been used in orthodontics as diagnostic aid or forensic tool. Therefore, this study was designed to explore the possible association of lip prints with skeletal malocclusion. Materials and Methods: A sample of 114 subjects in the age group of 18-30 years, from North Indian adult population were selected on the basis of skeletal class I, class II and class III malocclusion, each comprising of 38 subjects with equal number of males and females. Lip prints of all the individuals were recorded and digital soft copies of lateral cephalograms were taken. Lip prints were compared between different skeletal malocclusions. Results: It was found that branched lip pattern was most common in North Indian adult population with no sexual dimorphism. The Z-test for proportion showed that the prevalence of vertical lip pattern was significantly higher in subjects having skeletal class III malocclusion. Conclusion: A definite co-relation of vertical lip patterns with skeletal class III malocclusion was revealed. PMID:24255559

  3. Lip prints: The barcode of skeletal malocclusion

    Directory of Open Access Journals (Sweden)

    Pradeep Raghav

    2013-01-01

    Full Text Available Introduction: In orthodontics, apart from essential diagnostic aids, there are so many soft tissue analyses in which lips are major part of concern. However, lip prints have never been used in orthodontics as diagnostic aid or forensic tool. Therefore, this study was designed to explore the possible association of lip prints with skeletal malocclusion. Materials and Methods: A sample of 114 subjects in the age group of 18-30 years, from North Indian adult population were selected on the basis of skeletal class I, class II and class III malocclusion, each comprising of 38 subjects with equal number of males and females. Lip prints of all the individuals were recorded and digital soft copies of lateral cephalograms were taken. Lip prints were compared between different skeletal malocclusions. Results: It was found that branched lip pattern was most common in North Indian adult population with no sexual dimorphism. The Z-test for proportion showed that the prevalence of vertical lip pattern was significantly higher in subjects having skeletal class III malocclusion. Conclusion: A definite co-relation of vertical lip patterns with skeletal class III malocclusion was revealed.

  4. Impriniting of human H19: Allele-specific CpG methylation, loss of the active allele in Wilms tumor, and potential for somatic allele switching

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Shields, T.; Crenshaw, T.; Hao, Y.; Moulton, T.; Tycko, B. (Columbia Univ., New York (United States))

    1993-07-01

    Genomic imprinting and monoallelic gene expression appear to play a role in human genetic disease and tumorigenesis. The human H19 gene, at chromosome 11p15, has previously been shown to be monoallelically expressed. Since CpG methylation has been implicated in imprinting, the authors analyzed methylation of H19 DNA. In fetal and adult organs the transcriptionally silent H19 allele was extensively hypermethylated through the entire gene and its promoter, and, consistent with a functional role for DNA methylation, expression of an H19 promoter-reporter construct was inhibited by in vitro methylation. Gynogenetic ovarian teratomas were found to contain only hypomethylated H19 DNA, suggesting that the expressed H19 allele might be maternal. This was confirmed by analysis of 11p15 polymorphisms in a patient with Wilms tumor. The tumor had lost the maternal 11p15, and H19 expression in the normal kidney was exclusively from this allele. Imprinting of human H19 appears to be susceptible to tissue-specific modulation in somatic development; in one individual, cerebellar cells were found to express only the otherwise silent allele. Implications of these findings for the role of DNA methylation in imprinting and for H19 as a candidate imprinted tumor-suppressor gene are discussed. 57 refs., 7 figs.

  5. Allele-Specific Reduction of the Mutant Huntingtin Allele Using Transcription Activator-Like Effectors in Human Huntington's Disease Fibroblasts.

    Science.gov (United States)

    Fink, Kyle D; Deng, Peter; Gutierrez, Josh; Anderson, Joseph S; Torrest, Audrey; Komarla, Anvita; Kalomoiris, Stefanos; Cary, Whitney; Anderson, Johnathon D; Gruenloh, William; Duffy, Alexandra; Tempkin, Teresa; Annett, Geralyn; Wheelock, Vicki; Segal, David J; Nolta, Jan A

    2016-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an abnormal expansion of CAG repeats. Although pathogenesis has been attributed to this polyglutamine expansion, the underlying mechanisms through which the huntingtin protein functions have yet to be elucidated. It has been suggested that postnatal reduction of mutant huntingtin through protein interference or conditional gene knockout could prove to be an effective therapy for patients suffering from HD. For allele-specific targeting, transcription activator-like effectors (TALE) were designed to target single-nucleotide polymorphisms (SNP) in the mutant allele and packaged into a vector backbone containing KRAB to promote transcriptional repression of the disease-associated allele. Additional TALEs were packaged into a vector backbone containing heterodimeric FokI and were designed to be used as nucleases (TALEN) to cause a CAG-collapse in the mutant allele. Human HD fibroblasts were treated with each TALE-SNP or TALEN. Allele-expression was measured using a SNP-genotyping assay and mutant protein aggregation was quantified with Western blots for anti-ubiquitin. The TALE-SNP and TALEN significantly reduced mutant allele expression (p TALE proteins, and provides a foundation for targeted treatment for individuals suffering from Huntington's or other genetically linked diseases. PMID:26850319

  6. Characterization of chromosomal qnrB and ampC alleles in Citrobacter freundii isolates from different origins.

    Science.gov (United States)

    Liao, Xiaoping; Fang, Liangxing; Li, Liang; Sun, Jian; Li, Xingping; Chen, Muya; Deng, Hui; Yang, Qiu'e; Li, Xue; Liu, Yahong

    2015-10-01

    The association of ESBLs (extended-spectrum beta-lactamases)/pAmpCs (plasmid-mediated AmpC β-lactamases) with PMQR (plasmid mediated quinolone resistance) in gram-negative bacteria has been of great concern. The present study was performed to characterize the diversity, gene location, genetic context, and evolution of ampC and qnrB alleles in isolates of Citrobacter freundii. Fifteen isolates of C. freundii were identified from a total of 788 isolates of Enterobacteriaceae derived from humans, animals, animal food products, and the environment between 2010 and 2012. Co-existence of qnrB/ΔqnrB with ampC was detected in all C. freundii isolates. Both ampC and qnrB genes were found to be located on the chromosome, but were distantly separated on the chromosome. Seven and six novel alleles were discovered for the 10 ampC and qnrB variants detected in this study, respectively. Phylogenetic analysis showed that the new alleles differed a little from the variants of ampC/qnrB previously described in this genus. The genetic context surrounding ampC genes was AmpR-AmpC-Blc-SugE. However, five different genetic contexts surrounding qnrB/ΔqnrB genes were observed, but they occurred in all cases between the pspF and sapA genes. Additionally, cloning experiments showed that the regions containing different qnrB alleles, even with different genetic contexts, contributed to the reduction of quinolone susceptibility. Our results showed that the chromosomal ampC and qnrB alleles are closely related to C. freundii. However, unlike ampC, qnrB alleles seemed to be related to the genetic contexts surrounding them. The evolution of these two genes in C. freundii isolates might be through different pathways.

  7. Carnitine Palmitoyltransferase 1B 531K Allele Carriers Sustain a Higher Respiratory Quotient after Aerobic Exercise, but β3-Adrenoceptor 64R Allele Does Not Affect Lipolysis: A Human Model

    Science.gov (United States)

    Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

    2014-01-01

    Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat oxidation (through the non-protein respiratory quotient). These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise. PMID:24905907

  8. Carnitine palmitoyltransferase 1B 531K allele carriers sustain a higher respiratory quotient after aerobic exercise, but β3-adrenoceptor 64R allele does not affect lipolysis: a human model.

    Directory of Open Access Journals (Sweden)

    Eduardo Gómez-Gómez

    Full Text Available Carnitine palmitoyltransferase IB (CPT1B and adrenoceptor beta-3 (ADRB3 are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate and fat oxidation (through the non-protein respiratory quotient. These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise.

  9. Carnitine palmitoyltransferase 1B 531K allele carriers sustain a higher respiratory quotient after aerobic exercise, but β3-adrenoceptor 64R allele does not affect lipolysis: a human model.

    Science.gov (United States)

    Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

    2014-01-01

    Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat oxidation (through the non-protein respiratory quotient). These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise. PMID:24905907

  10. The benefits of coffee on skeletal muscle.

    Science.gov (United States)

    Dirks-Naylor, Amie J

    2015-12-15

    Coffee is consumed worldwide with greater than a billion cups of coffee ingested every day. Epidemiological studies have revealed an association of coffee consumption with reduced incidence of a variety of chronic diseases as well as all-cause mortality. Current research has primarily focused on the effects of coffee or its components on various organ systems such as the cardiovascular system, with relatively little attention on skeletal muscle. Summary of current literature suggests that coffee has beneficial effects on skeletal muscle. Coffee has been shown to induce autophagy, improve insulin sensitivity, stimulate glucose uptake, slow the progression of sarcopenia, and promote the regeneration of injured muscle. Much more research is needed to reveal the full scope of benefits that coffee consumption may exert on skeletal muscle structure and function.

  11. Intraurethral Injection of Autologous Minced Skeletal Muscle

    DEFF Research Database (Denmark)

    Gräs, Søren; Klarskov, Niels; Lose, Gunnar

    2014-01-01

    PURPOSE: Intraurethral injection of in vitro expanded autologous skeletal muscle derived cells is a new regenerative therapy for stress urinary incontinence. We examined the efficacy and safety of a simpler alternative strategy using freshly harvested, minced autologous skeletal muscle tissue with...... its inherent content of regenerative cells. MATERIALS AND METHODS: A total of 20 and 15 women with uncomplicated and complicated stress urinary incontinence, respectively, received intraurethral injections of minced autologous skeletal muscle tissue and were followed for 1 year. Efficacy was assessed...... events were noted. CONCLUSIONS: Intraurethral injection of minced autologous muscle tissue is a simple surgical procedure that appears safe and moderately effective in women with uncomplicated stress urinary incontinence. It compares well to a more complicated regenerative strategy using in vitro...

  12. Pannexin 1 channels in skeletal muscles

    OpenAIRE

    Cea, Luis A.; Riquelme, Manuel A.; Vargas, Anibal A.; Urrutia, Carolina; Sáez, Juan C.

    2014-01-01

    Normal myotubes and adult innervated skeletal myofibers express the glycoprotein pannexin1 (Panx1). Six of them form a “gap junction hemichannel-like” structure that connects the cytoplasm with the extracellular space; here they will be called Panx1 channels. These are poorly selective channels permeable to ions, small metabolic substrate, and signaling molecules. So far little is known about the role of Panx1 channels in muscles but skeletal muscles of Panx1−/− mice do not show an evident ph...

  13. Vasodilatory mechanisms in contracting skeletal muscle

    DEFF Research Database (Denmark)

    Clifford, Philip S.; Hellsten, Ylva

    2004-01-01

    Skeletal muscle blood flow is closely coupled to metabolic demand, and its regulation is believed to be mainly the result of the interplay of neural vasoconstrictor activity and locally derived vasoactive substances. Muscle blood flow is increased within the first second after a single contraction...... and stabilizes within 30 s during dynamic exercise under normal conditions. Vasodilator substances may be released from contracting skeletal muscle, vascular endothelium, or red blood cells. The importance of specific vasodilators is likely to vary over the time course of flow, from the initial rapid rise...

  14. Identification and characterization of variant alleles at CODIS STR loci.

    Science.gov (United States)

    Allor, Catherine; Einum, David D; Scarpetta, Marco

    2005-09-01

    Short tandem repeat (STR) profiles from 32,671 individuals generated by the ABI Profiler Plus and Cofiler systems were screened for variant alleles not represented within manufacturer-provided allelic ladders. A total of 85 distinct variants were identified at 12 of the 13 CODIS loci, most of which involve a truncated tetranucleotide repeat unit. Twelve novel alleles, identified at D3S1358, FGA, D18S51, D5S818, D7S820 and TPOX, were confirmed by nucleotide sequence analysis and include both insertions and deletions involving the repeat units themselves as well as DNA flanking the repeat regions. Population genetic data were collected for all variants and frequencies range from 0.0003 (many single observations) to 0.0042 (D7S820 '10.3' in North American Hispanics). In total, the variant alleles identified in this study are carried by 1.6% of the estimated 1 million individuals tested annually in the U.S. for the purposes of parentage resolution. A paternity case involving a recombination event of paternal origin is presented and demonstrates how variant alleles can significantly strengthen the genetic evidence in troublesome cases. In such instances, increased costs and turnaround time associated with additional testing may be eliminated.

  15. A Platform for Interrogating Cancer-Associated p53 Alleles

    Science.gov (United States)

    D’Brot, Alejandro; Kurtz, Paula; Regan, Erin; Jakubowski, Brandon; Abrams, John M

    2016-01-01

    p53 is the most frequently mutated gene in human cancer. Compelling evidence argues that full transformation involves loss of growth suppression encoded by wild-type p53 together with poorly understood oncogenic activity encoded by missense mutations. Furthermore, distinguishing disease alleles from natural polymorphisms is an important clinical challenge. To interrogate the genetic activity of human p53 variants, we leveraged the Drosophila model as an in vivo platform. We engineered strains that replace the fly p53 gene with human alleles, producing a collection of stocks that are, in effect, ‘humanized’ for p53 variants. Like the fly counterpart, human p53 transcriptionally activated a biosensor and induced apoptosis after DNA damage. However, all humanized strains representing common alleles found in cancer patients failed to complement in these assays. Surprisingly, stimulus-dependent activation of hp53 occurred without stabilization, demonstrating that these two processes can be uncoupled. Like its fly counterpart, hp53 formed prominent nuclear foci in germline cells but cancer-associated p53 variants did not. Moreover, these same mutant alleles disrupted hp53 foci and inhibited biosensor activity, suggesting that these properties are functionally linked. Together these findings establish a functional platform for interrogating human p53 alleles and suggest that simple phenotypes could be used to stratify disease variants. PMID:26996664

  16. Role of microRNAs in skeletal muscle hypertrophy

    OpenAIRE

    Hitachi, Keisuke; Tsuchida, Kunihiro

    2014-01-01

    Skeletal muscle comprises approximately 40% of body weight, and is important for locomotion, as well as for metabolic homeostasis. Adult skeletal muscle mass is maintained by a fine balance between muscle protein synthesis and degradation. In response to cytokines, nutrients, and mechanical stimuli, skeletal muscle mass is increased (hypertrophy), whereas skeletal muscle mass is decreased (atrophy) in a variety of conditions, including cancer cachexia, starvation, immobilization, aging, and n...

  17. Omega-3 Fatty Acids and Skeletal Muscle Health

    OpenAIRE

    Stewart Jeromson; Gallagher, Iain J.; Stuart D. R. Galloway; D. Lee Hamilton

    2015-01-01

    Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscl...

  18. Who are we missing? Too few skeletal surveys for children with humeral and femoral fractures

    International Nuclear Information System (INIS)

    Aim: To determine the potential shortfall in skeletal survey referral for children presenting with an acute non-supracondylar humeral or femoral fracture. Materials and methods: Plain radiograph reports were reviewed retrospectively using the radiology information system database over a 5 year study period (May 2008–2013) in children under 18 months of age who presented with an acute fracture. Subsequent skeletal survey referral was used as a surrogate marker for further investigation of child abuse. Application of robust meta-analysis derived probability data regarding likelihood of child abuse as a cause of non-supracondylar humeral or femoral fracture was applied. An estimation of the expected number of cases of abuse, with shortfall in skeletal survey referrals, was then calculated. Results: There were 288 fractures in 281 children. Three children presented with multiple fractures and were considered separately in the present data. The mean patient age was 10.5 months. Nine (3%) non-supracondylar humeral fractures were identified of which four cases may have been due to non-accidental injury (NAI). One (11%) of these patients was referred for a skeletal survey indicating a potential shortfall of three referrals. Twenty-five (9%) femoral fractures were identified of which 13 cases may have been due to NAI, with six (24%) referrals for skeletal surveys generated. This indicates a potential shortfall of seven referrals. Conclusion: The present study serves as a current analysis of practice within a tertiary paediatric referral centre. There appeared to be local under-investigation of NAI. Improved child protection education and awareness programmes have now been introduced. - Highlights: • Long bone fractures in non-ambulatory children carry high probability for child abuse. • Suspicion for child abuse should trigger a referral for a skeletal survey. • We examine the potential shortfall in skeletal survey referrals in such patients. • Only 11% and 24% of

  19. A strategy to discover genes that carry multi-allelic or mono-allelic risk for common diseases: A cohort allelic sums test (CAST)

    International Nuclear Information System (INIS)

    A method is described to discover if a gene carries one or more allelic mutations that confer risk for any specified common disease. The method does not depend upon genetic linkage of risk-conferring mutations to high frequency genetic markers such as single nucleotide polymorphisms. Instead, the sums of allelic mutation frequencies in case and control cohorts are determined and a statistical test is applied to discover if the difference in these sums is greater than would be expected by chance. A statistical model is presented that defines the ability of such tests to detect significant gene-disease relationships as a function of case and control cohort sizes and key confounding variables: zygosity and genicity, environmental risk factors, errors in diagnosis, limits to mutant detection, linkage of neutral and risk-conferring mutations, ethnic diversity in the general population and the expectation that among all exonic mutants in the human genome greater than 90% will be neutral with regard to any effect on disease risk. Means to test the null hypothesis for, and determine the statistical power of, each test are provided. For this 'cohort allelic sums test' or 'CAST', the statistical model and test are provided as an Excel (TM) program, CASTAT (C) at http://epidemiology.mit.edu. Based on genetics, technology and statistics, a strategy of enumerating the mutant alleles carried in the exons and splice sites of the estimated ∼25,000 human genes in case cohort samples of 10,000 persons for each of 100 common diseases is proposed and evaluated: A wide range of possible conditions of multi-allelic or mono-allelic and monogenic, multigenic or polygenic (including epistatic) risk are found to be detectable using the statistical criteria of 1 or 10 ''false positive'' gene associations per 25,000 gene-disease pair-wise trials and a statistical power of >0.8. Using estimates of the distribution of both neutral and gene-inactivating nondeleterious mutations in humans and

  20. Implication of HLA-DMA Alleles in Corsican IDDM

    Directory of Open Access Journals (Sweden)

    P. Cucchi-Mouillot

    1998-01-01

    Full Text Available The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

  1. Genetic Diversity Based on Allozyme Alleles of Chinese Cultivated Rice

    Institute of Scientific and Technical Information of China (English)

    TANG Sheng-xiang; WEI Xing-hua; JIANG Yun-zhu; D S Brar; G S Khush

    2007-01-01

    Genetic diversity was analyzed with 6 632 core rice cultivars selected from 60 282 Chinese rice accessions on the basis of 12 allozyme loci, Pgil, Pgi2, Ampl, Amp2, Amp3, Amp4, Sdh1, Adh1, Est1, Est2, Est5 and Est9, by starch gel electrophoresis. Among the materials examined, 52 alleles at 12 polymorphic loci were identified, which occupied 96.3% of 54 alleles found in cultivated germplasm of O.sativa L. The number of alleles per locus ranged from 2 to 7 with an average of 4.33. The gene diversity (He) each locus varied considerably from 0.017 for Amp4 to 0.583 for Est2 with an average gene diversity (Ht) 0.271, and Shannon-Wiener index from 0.055 to 0.946 with an average of 0.468. The degree of polymorphism (DP) was in a range from 0.9 to 46.9% with an average of 21.4%. It was found that the genetic diversity in japonica (Keng) subspecies was lower in terms of allele's number, Ht and S-W index, being 91.8, 66.2 and 75.7% of indica (Hsien) one, respectively. Significant genetic differentiation between indica and japonica rice has been appeared in the loci Pgil, Amp2, Pgi2, and Est2, with higher average coefficient of genetic differentiation (Gst) 0.635, 0.626, 0.322 and 0.282, respectively. Except less allele number per locus (3.33) for modern cultivars, being 76.9% of landraces, the Ht and S-W index showed in similar between the modern cultivars and the landraces detected. In terms of allozyme, the rice cultivars in the Southwest Plateau and Central China have richer genetic diversity. The present study reveals again that Chinese cultivated rice germplasm has rich genetic diversity, showed by the allozyme allele variation.

  2. A common mutation associated with the Duarte galactosemia allele

    Energy Technology Data Exchange (ETDEWEB)

    Elsas, L.J.; Dembure, P.P.; Langley, S.; Paulk, E.M.; Hjelm, L.N.; Fridovich-Keil, J. (Emory Univ. School of Medicine, Atlanta, GA (United States))

    1994-06-01

    The human cDNA and gene for galactose-1-phosphate uridyl transferase (GALT) have been cloned and sequenced. A prevalant mutation (Q188R) is known to cause classic galactosemia (G/G). G/G galactosemia has an incidence of 1/38,886 in 1,396,766 Georgia live-born infants, but a more common variant of galactosemia, Duarte, has an unknown incidence. The proposed Duarte biochemical phenotypes of GALT are as follows: D/N, D/D, and D/G, which have [approximately]75%, 50%, and 25% of normal GALT activity, respectively. In addition, the D allele has isoforms of its enzyme that have more acidic pI than normal. Here the authors systematically determine (a) the prevalence of an A-to-G transition at base pair 2744 of exon 10 in the GALT gene, a transition that produces a codon change converting asparagine to aspartic acid at position 314 (N314D), and (b) the association of this mutation with the Duarte biochemical phenotype. The 2744G nucleotide change adds an AvaII (SinI) cut site, which was identified in PCR-amplified DNA. In 111 biochemically unphenotyped controls with no history of galactosemia, 13 N314D alleles were identified (prevalence 5.9%). In a prospective study, 40 D alleles were biochemically phenotyped, and 40 N314D alleles were found. By contrast, in 36 individuals known not to have the Duarte biochemical phenotype, no N314D alleles were found. The authors conclude that the N314D mutation is a common allele that probably causes the Duarte GALT biochemical phenotype and occurs in a predominantly Caucasian, nongalactosemic population, with a prevalence of 5.9%. 36 refs., 3 figs., 2 tabs.

  3. Allele-specific DNA methylation reinforces PEAR1 enhancer activity.

    Science.gov (United States)

    Izzi, Benedetta; Pistoni, Mariaelena; Cludts, Katrien; Akkor, Pinar; Lambrechts, Diether; Verfaillie, Catherine; Verhamme, Peter; Freson, Kathleen; Hoylaerts, Marc F

    2016-08-18

    Genetic variation in the PEAR1 locus is linked to platelet reactivity and cardiovascular disease. The major G allele of rs12041331, an intronic cytosine guanine dinucleotide-single-nucleotide polymorphism (CpG-SNP), is associated with higher PEAR1 expression in platelets and endothelial cells than the minor A allele. The molecular mechanism underlying this difference remains elusive. We have characterized the histone modification profiles of the intronic region surrounding rs12041331 and identified H3K4Me1 enhancer-specific enrichment for the region that covers the CpG-SNP. Interestingly, methylation studies revealed that the CpG site is fully methylated in leukocytes of GG carriers. Nuclear protein extracts from megakaryocytes, endothelial cells, vs control HEK-293 cells show a 3-fold higher affinity for the methylated G allele compared with nonmethylated G or A alleles in a gel electrophoretic mobility shift assay. To understand the positive relationship between methylation and gene expression, we studied DNA methylation at 4 different loci of PEAR1 during in vitro megakaryopoiesis. During differentiation, the CpG-SNP remained fully methylated, while we observed rapid methylation increases at the CpG-island overlapping the first 5'-untranslated region exon, paralleling the increased PEAR1 expression. In the same region, A-allele carriers of rs12041331 showed significantly lower DNA methylation at CGI1 compared with GG homozygote. This CpG-island contains binding sites for the methylation-sensitive transcription factor CTCF, whose binding is known to play a role in enhancer activation and/or repression. In conclusion, we report the molecular characterization of the first platelet function-related CpG-SNP, a genetic predisposition that reinforces PEAR1 enhancer activity through allele-specific DNA methylation. PMID:27313330

  4. Distribution of a pseudodeficiency allele among Tay-Sachs carriers

    Energy Technology Data Exchange (ETDEWEB)

    Tomczak, J.; Grebner, E.E. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Boogen, C. (Univ. of Essen Medical School (Germany))

    1993-08-01

    Recently Triggs-Raine et al. (1992) identified a new mutation in the gene coding for the [alpha]-subunit of [beta]-hexosaminidase A (hex A), the enzyme whose deficiency causes Tay-Sachs disease. This mutation, a C[sub 739]-to-T transition in exon 7, results in an altered enzyme that is active (albeit at reduced levels) in cells but that has essentially no activity in serum. This so-called pseudodeficient allele was first detected in compound heterozygotes who also carried a Tay-Sachs disease allele and therefore had no detectable hex A in their serum but who were in good health. Carriers of this apparently benign mutation are generally indistinguishable from carriers of a lethal mutation by means of routine enzyme-based screening tests, because the product of the pseudodeficient allele is not detectable in serum and has decreased activity in cells. This suggests that some individuals who have been classified as Tay-Sachs carriers are actually carriers of the pseudodeficient allele and are not at risk to have a child affected with Tay-Sachs disease. The pseudodeficient allele may also be responsible for some inconclusive diagnoses, where leukocyte values fall below the normal range but are still above the carrier range. The fact that there are now two mutant alleles (the psuedodeficient and the adult) that are indistinguishable from the lethal infantile mutations by means of enzyme assay yet that are phenotypically very different and that together may account for as much as 12% of enzyme-defined carriers on the basis of the data here suggests that DNA analysis should be part of a comprehensive screening program. It will be particularly useful to identify the mutations in couples at risk, before they undergo prenatal diagnosis. DNA analysis will also resolve some inconclusive diagnoses.

  5. The inheritance of resistance alleles in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Sreeram V Ramagopalan

    2007-09-01

    Full Text Available Multiple sclerosis (MS is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. HLA-DRB1*15 and HLA-DRB1*17-bearing haplotypes and interactions at the HLA-DRB1 locus increase risk of MS but it has taken large samples to identify resistance HLA-DRB1 alleles. In this investigation of 7,093 individuals from 1,432 MS families, we have assessed the validity, mode of inheritance, associated genotypes, and the interactions of HLA-DRB1 resistance alleles. HLA-DRB1*14-, HLA-DRB1*11-, HLA-DRB1*01-, and HLA-DRB1*10-bearing haplotypes are protective overall but they appear to operate by different mechanisms. The first type of resistance allele is characterised by HLA-DRB1*14 and HLA-DRB1*11. Each shows a multiplicative mode of inheritance indicating a broadly acting suppression of risk, but a different degree of protection. In contrast, a second type is exemplified by HLA-DRB1*10 and HLA-DRB1*01. These alleles are significantly protective when they interact specifically in trans with HLA-DRB1*15-bearing haplotypes. HLA-DRB1*01 and HLA-DRB1*10 do not interact with HLA-DRB1*17, implying that several mechanisms may be operative in major histocompatibility complex-associated MS susceptibility, perhaps analogous to the resistance alleles. There are major practical implications for risk and for the exploration of mechanisms in animal models. Restriction of antigen presentation by HLA-DRB1*15 seems an improbably simple mechanism of major histocompatibility complex-associated susceptibility.

  6. A common allele on chromosome 9 associated with coronary heartdisease

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, Ruth; Pertsemlidis, Alexander; Kavaslar, Nihan; Stewart, Alexandre; Roberts, Robert; Cox, David R.; Hinds, David; Pennachio, Len; Tybjaerg-Hansen, Anne; Folsom, Aaron R.; Boerwinkle,Eric; Hobbs, Helen H.; Cohen, Jonathan C.

    2007-03-01

    Coronary heart disease (CHD) is a major cause of death in Western countries. Here we used genome-wide association scanning to identify a 58 kb interval on chromosome 9 that was consistently associated with CHD in six independent samples. The interval contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension or diabetes. Homozygotes for the risk allele comprise 20-25% of Caucasians and have a {approx}30-40% increased risk of CHD. These data indicate that the susceptibility allele acts through a novel mechanism to increase CHD risk in a large fraction of the population.

  7. Mechanotransduction pathways in skeletal muscle hypertrophy.

    Science.gov (United States)

    Yamada, André Katayama; Verlengia, Rozangela; Bueno Junior, Carlos Roberto

    2012-02-01

    In the last decade, molecular biology has contributed to define some of the cellular events that trigger skeletal muscle hypertrophy. Recent evidence shows that insulin like growth factor 1/phosphatidyl inositol 3-kinase/protein kinase B (IGF-1/PI3K/Akt) signaling is not the main pathway towards load-induced skeletal muscle hypertrophy. During load-induced skeletal muscle hypertrophy process, activation of mTORC1 does not require classical growth factor signaling. One potential mechanism that would activate mTORC1 is increased synthesis of phosphatidic acid (PA). Despite the huge progress in this field, it is still early to affirm which molecular event induces hypertrophy in response to mechanical overload. Until now, it seems that mTORC1 is the key regulator of load-induced skeletal muscle hypertrophy. On the other hand, how mTORC1 is activated by PA is unclear, and therefore these mechanisms have to be determined in the following years. The understanding of these molecular events may result in promising therapies for the treatment of muscle-wasting diseases. For now, the best approach is a good regime of resistance exercise training. The objective of this point-of-view paper is to highlight mechanotransduction events, with focus on the mechanisms of mTORC1 and PA activation, and the role of IGF-1 on hypertrophy process. PMID:22171534

  8. Mechanotransduction pathways in skeletal muscle hypertrophy.

    Science.gov (United States)

    Yamada, André Katayama; Verlengia, Rozangela; Bueno Junior, Carlos Roberto

    2012-02-01

    In the last decade, molecular biology has contributed to define some of the cellular events that trigger skeletal muscle hypertrophy. Recent evidence shows that insulin like growth factor 1/phosphatidyl inositol 3-kinase/protein kinase B (IGF-1/PI3K/Akt) signaling is not the main pathway towards load-induced skeletal muscle hypertrophy. During load-induced skeletal muscle hypertrophy process, activation of mTORC1 does not require classical growth factor signaling. One potential mechanism that would activate mTORC1 is increased synthesis of phosphatidic acid (PA). Despite the huge progress in this field, it is still early to affirm which molecular event induces hypertrophy in response to mechanical overload. Until now, it seems that mTORC1 is the key regulator of load-induced skeletal muscle hypertrophy. On the other hand, how mTORC1 is activated by PA is unclear, and therefore these mechanisms have to be determined in the following years. The understanding of these molecular events may result in promising therapies for the treatment of muscle-wasting diseases. For now, the best approach is a good regime of resistance exercise training. The objective of this point-of-view paper is to highlight mechanotransduction events, with focus on the mechanisms of mTORC1 and PA activation, and the role of IGF-1 on hypertrophy process.

  9. Interleukin-6 myokine signaling in skeletal muscle

    DEFF Research Database (Denmark)

    Muñoz-Cánoves, Pura; Scheele, Camilla; Pedersen, Bente K;

    2013-01-01

    Interleukin (IL)-6 is a cytokine with pleiotropic functions in different tissues and organs. Skeletal muscle produces and releases significant levels of IL-6 after prolonged exercise and is therefore considered as a myokine. Muscle is also an important target of the cytokine. IL-6 signaling has b...

  10. Tissue engineering skeletal muscle for orthopaedic applications

    Science.gov (United States)

    Payumo, Francis C.; Kim, Hyun D.; Sherling, Michael A.; Smith, Lee P.; Powell, Courtney; Wang, Xiao; Keeping, Hugh S.; Valentini, Robert F.; Vandenburgh, Herman H.

    2002-01-01

    With current technology, tissue-engineered skeletal muscle analogues (bioartificial muscles) generate too little active force to be clinically useful in orthopaedic applications. They have been engineered genetically with numerous transgenes (growth hormone, insulinlike growth factor-1, erythropoietin, vascular endothelial growth factor), and have been shown to deliver these therapeutic proteins either locally or systemically for months in vivo. Bone morphogenetic proteins belonging to the transforming growth factor-beta superfamily are osteoinductive molecules that drive the differentiation pathway of mesenchymal cells toward the chondroblastic or osteoblastic lineage, and stimulate bone formation in vivo. To determine whether skeletal muscle cells endogenously expressing bone morphogenetic proteins might serve as a vehicle for systemic bone morphogenetic protein delivery in vivo, proliferating skeletal myoblasts (C2C12) were transduced with a replication defective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6). The C2BMP-6 cells constitutively expressed recombinant human bone morphogenetic protein-6 and synthesized bioactive recombinant human bone morphogenetic protein-6, based on increased alkaline phosphatase activity in coincubated mesenchymal cells. C2BMP-6 cells did not secrete soluble, bioactive recombinant human bone morphogenetic protein-6, but retained the bioactivity in the cell layer. Therefore, genetically-engineered skeletal muscle cells might serve as a platform for long-term delivery of osteoinductive bone morphogenetic proteins locally.

  11. Training induced adaptation in horse skeletal muscle

    NARCIS (Netherlands)

    Dam, K.G. van

    2006-01-01

    It appears that the physiological and biochemical adaptation of skeletal muscle to training in equine species shows a lot of similarities with human and rodent physiological adaptation. On the other hand it is becoming increasingly clear that intra-cellular mechanisms of adaptation (substrate transp

  12. Engineering skeletal muscle tissue in bioreactor systems

    Institute of Scientific and Technical Information of China (English)

    An Yang; Li Dong

    2014-01-01

    Objective To give a concise review of the current state of the art in tissue engineering (TE) related to skeletal muscle and kinds of bioreactor environment.Data sources The review was based on data obtained from the published articles and guidelines.Study selection A total of 106 articles were selected from several hundred original articles or reviews.The content of selected articles is in accordance with our purpose and the authors are authorized scientists in the study of engineered muscle tissue in bioreactor.Results Skeletal muscle TE is a promising interdisciplinary field which aims at the reconstruction of skeletal muscle loss.Although numerous studies have indicated that engineering skeletal muscle tissue may be of great importance in medicine in the near future,this technique still represents a limited degree of success.Since tissue-engineered muscle constructs require an adequate connection to the vascular system for efficient transport of oxygen,carbon dioxide,nutrients and waste products.Moreover,functional and clinically applicable muscle constructs depend on adequate neuromuscular junctions with neural calls.Third,in order to engineer muscle tissue successfully,it may be beneficial to mimic the in vivo environment of muscle through association with adequate stimuli from bioreactors.Conclusion Vascular system and bioreactors are necessary for development and maintenance of engineered muscle in order to provide circulation within the construct.

  13. Space travel directly induces skeletal muscle atrophy

    Science.gov (United States)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  14. AMPK controls exercise endurance, mitochondrial oxidative capacity, and skeletal muscle integrity. : AMPK in skeletal musclemetabolic adaptation

    OpenAIRE

    Lantier, Louise; Fentz, Joachim; Mounier, Rémi; Leclerc, Jocelyne; Treebak, Jonas,; Pehmøller, Christian; Sanz, Nieves; Sakakibara, Iori; Saint-Amand, Emmanuelle; Rimbaud, Stéphanie; Maire, Pascal; Marette, André; Ventura-Clapier, Renée; Ferry, Arnaud; Wojtaszewski, Jørgen,

    2014-01-01

    : AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that plays a central role in skeletal muscle metabolism. We used skeletal muscle-specific AMPKα1α2 double-knockout (mdKO) mice to provide direct genetic evidence of the physiological importance of AMPK in regulating muscle exercise capacity, mitochondrial function, and contraction-stimulated glucose uptake. Exercise performance was significantly reduced in the mdKO mice, with a reduction in maximal force production an...

  15. Skeletal Stability after Large Mandibular Advancement (> 10 mm) with Bilateral Sagittal Split Osteotomy and Skeletal Elastic Intermaxillary Fixation

    DEFF Research Database (Denmark)

    Schwartz, Kristoffer; Rodrigo, Maria; Jensen, Thomas

    2016-01-01

    OBJECTIVES: The aim of the present study was to assess the skeletal stability after large mandibular advancement (> 10 mm) with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation and to correlate the skeletal stability with the vertical facial type. MATERIAL AND METHO...... to distraction osteogenesis in large mandibular advancements....

  16. Further data on the microsatellite locus D12S67 in worldwide populations: an unusual distribution of D12S67 alleles in Native Americans.

    Science.gov (United States)

    Mitchell, R J; Federle, L; Sofro, A S; Papiha, S S; Briceno, I; Bernal, J E

    2000-08-01

    We report the frequencies of alleles at the microsatellite locus D12S67 in 2 widely separated ethnic groups of the world: 2 populations from Sulawesi, an island in the Indonesian archipelago, and 5 Native American tribes of Colombia, South America. The allele frequencies in the Minihasans and Torajans of Sulawesi are similar to each other (but the modal class allele is different) and in general agreement with those reported in mainland Asian groups, but different from both Europeans and Chinese Han of Taiwan. The 5 Native American tribes (Arsario, Kogui, Ijka, Wayuu, and Coreguaje) display different allele frequencies from those seen in Sulawesi populations, in other groups from Europe and mainland Asia, and in Chinese Han of Taiwan. Native Americans exhibit a bimodal distribution of alleles, unlike other groups, with significant differences among the tribes. The Arsario and Kogui have no admixture with Europeans or Africans and are the most distinctive, while the Wayuu have the most admixture and show most similarity to other groups. The data suggest that nonadmixed Native Americans may be quite distinctive with respect to this marker. The most common allele varies across the 5 tribes, from 249 base pairs to 261 base pairs. All samples exhibit Hardy-Weinberg genotype proportions; heterozygosities are lowest in the 2 nonadmixed Native American tribes. Examination of all the available data indicates that some east Asian and southeast Asian groups are characterized by a high frequency of smaller sized D12S67 alleles, while other populations have a greater proportion of the larger sized alleles. The cumulative, though still highly restricted, population data on locus D12S67 demonstrate that it may be of considerable value in anthropological genetic studies of ethnic groups. Data are required on Native Americans outside Colombia before this marker can be used in admixture studies of this group. PMID:11048795

  17. Ultra-deep Illumina sequencing accurately identifies MHC class IIb alleles and provides evidence for copy number variation in the guppy (Poecilia reticulata).

    Science.gov (United States)

    Lighten, Jackie; van Oosterhout, Cock; Paterson, Ian G; McMullan, Mark; Bentzen, Paul

    2014-07-01

    We address the bioinformatic issue of accurately separating amplified genes of the major histocompatibility complex (MHC) from artefacts generated during high-throughput sequencing workflows. We fit observed ultra-deep sequencing depths (hundreds to thousands of sequences per amplicon) of allelic variants to expectations from genetic models of copy number variation (CNV). We provide a simple, accurate and repeatable method for genotyping multigene families, evaluating our method via analyses of 209 b of MHC class IIb exon 2 in guppies (Poecilia reticulata). Genotype repeatability for resequenced individuals (N = 49) was high (100%) within the same sequencing run. However, repeatability dropped to 83.7% between independent runs, either because of lower mean amplicon sequencing depth in the initial run or random PCR effects. This highlights the importance of fully independent replicates. Significant improvements in genotyping accuracy were made by greatly reducing type I genotyping error (i.e. accepting an artefact as a true allele), which may occur when using low-depth allele validation thresholds used by previous methods. Only a small amount (4.9%) of type II error (i.e. rejecting a genuine allele as an artefact) was detected through fully independent sequencing runs. We observed 1-6 alleles per individual, and evidence of sharing of alleles across loci. Variation in the total number of MHC class II loci among individuals, both among and within populations was also observed, and some genotypes appeared to be partially hemizygous; total allelic dosage added up to an odd number of allelic copies. Collectively, observations provide evidence of MHC CNV and its complex basis in natural populations.

  18. Magnetic resonance imaging of the skeletal musculature

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Marc-Andre (ed.) [Univ. Hospital Heidelberg (Germany). Diagnostic and Intverventional Radiology

    2014-07-01

    Comprehensive overview of the value of cutting-edge MRI for the assessment of normal and diseased skeletal muscle. Presents research findings in respect of the role of modern morphological and functional MRI techniques. Provides examples of the added value provided by these techniques when evaluating muscular diseases. Although muscular diseases are a huge and heterogeneous group, in most cases of progressive disease the result is focal or general muscular weakness that presents as an unspecific symptom. Imaging techniques that offer differential diagnostic clues are therefore urgently needed. Despite this, MRI has to date often been assigned a subsidiary role in the diagnostic work-up of these diseases owing to the frequent inability of routine MRI protocols to detect pathognomonic findings. This situation is changing with the advent of modern MRI techniques that offer deeper insights into surrogate pathophysiologic parameters, such as muscular microcirculation, sodium homeostasis, energy and lipid metabolism, and muscle fiber architecture. Much higher levels of acceptance and demand by clinicians can be anticipated for these new techniques in the near future, and radiologists will have to face up to the increasing value of MRI of the skeletal musculature. In this book, recognized experts from around the world provide a comprehensive overview of the value of cutting-edge MRI for the assessment of normal and diseased skeletal muscle. A range of aspects are covered, from the general role of MRI in imaging the skeletal musculature, including in comparison with ultrasonography, through to the current value of MRI in the diagnostic work-up of different diseases. In addition, several chapters present research findings in respect of modern morphological and functional MRI techniques for assessment of the skeletal musculature and provide examples of the added value provided by these techniques when evaluating muscular diseases.

  19. A WIDE DISTRIBUTION OF A NEW VRN-B1c ALLELE OF WHEAT TRITICUM AESTIVUM L. IN RUSSIA, UKRAINE AND ADJACENT REGIONS: A LINK WITH THE HEADING TIME AND ADAPTIVE POTENTIAL

    Directory of Open Access Journals (Sweden)

    Shcherban A.

    2012-08-01

    Full Text Available The adaptation of common wheat (T. aestivum L. to diverse environmental conditions is greatly under the control of genes involved in determination of vernalization response (Vrn-1 genes. It was found that the variation in common wheat heading time is affected not only by combination of Vrn-1 homoeoalleles but also by multiple alleles at a separate Vrn-1 locus. Previously, we described the Vrn-B1c allele from T.aestivum cv. 'Saratovskaya 29' and found significant differences in the structure of the first (1st intron of this allele when compared to another highly abundant Vrn-B1a allele, specifically, the deletion of 0.8 kb coupled with the duplication of 0.4 kb. We suggested that the changes in the intron 1 of Vrn-B1c allele caused earlier ear emergence in the near-isogenic line and cultivars, carrying this allele. In this study we investigate the distribution of the Vrn-B1c allele in a wide set of spring wheat cultivars from Russia, Ukraine and adjacent regions. The analysis revealed that 40% of Russian and 53% of Ukranian spring wheat cultivars contain the Vrn-B1c allele. The high distribution of the Vrn-B1c allele can be explained by a frequent using of 'Saratovskaya 29' in the breeding process inside the studied area. From the other hand, the predominance of the Vrn-B1c allele among cultivars cultivated in West Siberia and Kazakhstan may be due to the selective advantage of this allele for the region where there is a high risk of early fall frosts.

  20. Inheritance and interactions of incompatibility alleles in the tetraploid sour cherry.

    Science.gov (United States)

    Bosković, R I; Wolfram, B; Tobutt, K R; Cerović, R; Sonneveld, T

    2006-01-01

    Three progenies of sour cherry (Prunus cerasus) were analysed to correlate self-(in)compatibility status with S-RNase phenotype in this allotetraploid hybrid of sweet and ground cherry. Self-(in)compatibility was assessed in the field and by monitoring pollen tube growth after selfing. The S-RNase phenotypes were determined by isoelectric focusing of stylar proteins and staining for RNase activity and, for the parents, confirmed by PCR. Seedling phenotypes were generally consistent with disomic segregation of S-RNase alleles. The genetic arrangements of the parents were deduced to be 'Köröser' (self-incompatible) S1S4.S(B) S(D), 'Schattenmorelle' (self-compatible) S6S13.S(B)S(B), and clone 43.87 (self-compatible) S4S13.S(B)S(B), where "." separates the two homologous genomes. The presence of S4 and S6 alleles at the same locus led to self-incompatibility, whereas S13 and S(B) at homologous loci led to self-compatibility. The failure of certain heteroallelic genotypes in the three crosses or in the self-incompatible seedlings indicates that S4 and S6 are dominant to S(B). However, the success of S13S(B) pollen on styles expressing corresponding S-RNases indicates competitive interaction or lack of pollen-S components. In general, the universal compatibility of S13S(B) pollen may explain the frequent occurrence of S13 and S(B) together in sour cherry cultivars. Alleles S(B) and S(D), that are presumed to derive from ground cherry, and S13, presumably from sweet cherry, were sequenced. Our findings contribute to an understanding of inheritance of self-(in)compatibility, facilitate screening of progenies for self-compatibility and provide a basis for studying molecular interactions in heteroallelic pollen. PMID:16307228

  1. Impact of autoimmune risk alleles on the immune system

    OpenAIRE

    Ray, John P.; Hacohen, Nir

    2015-01-01

    Genetic analyses of autoimmune diseases have revealed hundreds of disease-associated DNA variants, but the identity and function of the causal variants are understudied and warrant deeper mechanistic studies. Here, we highlight methods for deciphering how alleles that are associated with autoimmune disease alter the human immune system, and suggest strategies for future autoimmune genetic research.

  2. Disease-Causing Allele-Specific Silencing by RNA Interference

    Directory of Open Access Journals (Sweden)

    Hirohiko Hohjoh

    2013-04-01

    Full Text Available Small double-stranded RNAs (dsRNAs of approximately 21-nucleotides in size, referred to as small interfering RNA (siRNA duplexes, can induce sequence-specific posttranscriptional gene silencing, or RNA interference (RNAi. Since chemically synthesized siRNA duplexes were found to induce RNAi in mammalian cells, RNAi has become a powerful reverse genetic tool for suppressing the expression of a gene of interest in mammals, including human, and its application has been expanding to various fields. Recent studies further suggest that synthetic siRNA duplexes have the potential for specifically inhibiting the expression of an allele of interest without suppressing the expression of other alleles, i.e., siRNA duplexes likely confer allele-specific silencing. Such gene silencing by RNAi is an advanced technique with very promising applications. In this review, I would like to discuss the potential utility of allele-specific silencing by RNAi as a therapeutic method for dominantly inherited diseases, and describe possible improvements in siRNA duplexes for enhancing their efficacy.

  3. Distribution of forensic marker allelic frequencies in Pernambuco, Northestern Brazil.

    Science.gov (United States)

    Santos, S M; Souza, C A; Rabelo, K C N; Souza, P R E; Moura, R R; Oliveira, T C; Crovella, S

    2015-01-01

    Pernambuco is one of the 27 federal units of Brazil, ranking seventh in the number of inhabitants. We examined the allele frequencies of 13 short tandem repeat loci (CFS1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, vWA, and TPOX), the minimum recommended by the Federal Bureau of Investigation and commonly used in forensic genetics laboratories in Brazil, in a sample of 609 unrelated individuals from all geographic regions of Pernambuco. The allele frequencies ranged from 5 to 47.2%. No significant differences for any loci analyzed were observed compared with other publications in other various regions of Brazil. Most of the markers observed were in Hardy-Weinberg equilibrium. The occurrence of the allele 47.2 (locus FGA) and alleles 35.1 and 39 (locus D21S11), also described in a single study of the Brazilian population, was observed. The other forensic parameters analyzed (matching probability, power of discrimination, polymorphic information content, paternity exclusion, complement factor I, observed heterozygosity, expected heterozygosity) indicated that the studied markers are very informative for human forensic identification purposes in the Pernambuco population. PMID:25966202

  4. Estimating the age of alleles by use of intraallelic variability

    Energy Technology Data Exchange (ETDEWEB)

    Slatkin, M.; Rannala, B. [Univ of California, Berkeley, CA (United States)

    1997-02-01

    A method is presented for estimating the age of an allele by use of its frequency and the extent of variation among different copies. The method uses the joint distribution of the number of copies in a population sample and the coalescence times of the intraallelic gene genealogy conditioned on the number of copies. The linear birth-death process is used to approximate the dynamics of a rare allele in a finite population. A maximum-likelihood estimate of the age of the allele is obtained by Monte Carlo integration over the coalescence times. The method is applied to two alleles at the cystic fibrosis (CFTR) locus, {Delta}F508 and G542X, for which intraallelic variability at three intronic microsatellite loci has been examined. Our results indicate that G542X is somewhat older than {Delta}F508. Although absolute estimates depend on the mutation rates at the microsatellite loci, our results support the hypothesis that {Delta}F508 arose <500 generations ({approx}10,000 years) ago. 32 refs., 4 figs.

  5. Short mucin 6 alleles are associated with H pylori infection

    Institute of Scientific and Technical Information of China (English)

    Thai V Nguyen; Marcel JR Janssen; Paulien Gritters; René HM te Morsche; Joost PH Drenth; Henri van Asten; Robert JF Laheij; Jan BMJ Jansen

    2006-01-01

    AIM: To investigate the relationship between mucin 6(MUC6) VNTR length and H pylori infection.METHODS: Blood samples were collected from patients visiting the Can Tho General Hospital for upper gastrointestinal endoscopy. DNA was isolated from whole blood, the repeated section was cut out using a restriction enzyme (Pvu Ⅱ) and the length of the allele fragments was determined by Southern blotting. H pylori infection was diagnosed by 14C urea breath test. For analysis, MUC6 allele fragment length was dichotomized as being either long (> 13.5 kbp) or short (≤ 13.5 kbp)and patients were classified according to genotype [long-long (LL), long-short (LS), short-short (SS)].RESULTS: 160 patients were studied (mean age 43years, 36% were males, 58% H pylori positive). MUC6Pvu Ⅱ-restricted allele fragment lengths ranged from 7 to 19 kbp. Of the patients with the LL, LS, SS MUC6genotype, 43% (24/56), 57% (25/58) and 76% (11/46)were infected with H pylori, respectively (P = 0.003).CONCLUSION: Short MUC6 alleles are associated with H pylori infection.

  6. TrueAllele casework on Virginia DNA mixture evidence: computer and manual interpretation in 72 reported criminal cases.

    Directory of Open Access Journals (Sweden)

    Mark W Perlin

    Full Text Available Mixtures are a commonly encountered form of biological evidence that contain DNA from two or more contributors. Laboratory analysis of mixtures produces data signals that usually cannot be separated into distinct contributor genotypes. Computer modeling can resolve the genotypes up to probability, reflecting the uncertainty inherent in the data. Human analysts address the problem by simplifying the quantitative data in a threshold process that discards considerable identification information. Elevated stochastic threshold levels potentially discard more information. This study examines three different mixture interpretation methods. In 72 criminal cases, 111 genotype comparisons were made between 92 mixture items and relevant reference samples. TrueAllele computer modeling was done on all the evidence samples, and documented in DNA match reports that were provided as evidence for each case. Threshold-based Combined Probability of Inclusion (CPI and stochastically modified CPI (mCPI analyses were performed as well. TrueAllele's identification information in 101 positive matches was used to assess the reliability of its modeling approach. Comparison was made with 81 CPI and 53 mCPI DNA match statistics that were manually derived from the same data. There were statistically significant differences between the DNA interpretation methods. TrueAllele gave an average match statistic of 113 billion, CPI averaged 6.68 million, and mCPI averaged 140. The computer was highly specific, with a false positive rate under 0.005%. The modeling approach was precise, having a factor of two within-group standard deviation. TrueAllele accuracy was indicated by having uniformly distributed match statistics over the data set. The computer could make genotype comparisons that were impossible or impractical using manual methods. TrueAllele computer interpretation of DNA mixture evidence is sensitive, specific, precise, accurate and more informative than manual

  7. TrueAllele casework on Virginia DNA mixture evidence: computer and manual interpretation in 72 reported criminal cases.

    Science.gov (United States)

    Perlin, Mark W; Dormer, Kiersten; Hornyak, Jennifer; Schiermeier-Wood, Lisa; Greenspoon, Susan

    2014-01-01

    Mixtures are a commonly encountered form of biological evidence that contain DNA from two or more contributors. Laboratory analysis of mixtures produces data signals that usually cannot be separated into distinct contributor genotypes. Computer modeling can resolve the genotypes up to probability, reflecting the uncertainty inherent in the data. Human analysts address the problem by simplifying the quantitative data in a threshold process that discards considerable identification information. Elevated stochastic threshold levels potentially discard more information. This study examines three different mixture interpretation methods. In 72 criminal cases, 111 genotype comparisons were made between 92 mixture items and relevant reference samples. TrueAllele computer modeling was done on all the evidence samples, and documented in DNA match reports that were provided as evidence for each case. Threshold-based Combined Probability of Inclusion (CPI) and stochastically modified CPI (mCPI) analyses were performed as well. TrueAllele's identification information in 101 positive matches was used to assess the reliability of its modeling approach. Comparison was made with 81 CPI and 53 mCPI DNA match statistics that were manually derived from the same data. There were statistically significant differences between the DNA interpretation methods. TrueAllele gave an average match statistic of 113 billion, CPI averaged 6.68 million, and mCPI averaged 140. The computer was highly specific, with a false positive rate under 0.005%. The modeling approach was precise, having a factor of two within-group standard deviation. TrueAllele accuracy was indicated by having uniformly distributed match statistics over the data set. The computer could make genotype comparisons that were impossible or impractical using manual methods. TrueAllele computer interpretation of DNA mixture evidence is sensitive, specific, precise, accurate and more informative than manual interpretation alternatives

  8. Proteomic profiling reveals a severely perturbed protein expression pattern in aged skeletal muscle.

    Science.gov (United States)

    O'Connell, Kathleen; Gannon, Joan; Doran, Philip; Ohlendieck, Kay

    2007-08-01

    Extended longevity is often accompanied by frailty and increased susceptibility to a variety of crippling disorders. One of the most striking features of human aging is sarcopenia, which is defined as the age-related decline in skeletal muscle mass and strength. Although various metabolic and functional defects in aging muscle fibres have been described over the last decade, it is not known whether a pathophysiological hierarchy exists within degenerative pathways leading to muscle wasting. Hence, in order to identify novel biomarkers of age-dependent skeletal muscle degeneration, we have here applied mass spectrometry-based proteomics for studying global muscle protein expression patterns. As a model system of sarcopenia, we have employed crude extracts from senescent rat gastrocnemius muscle, as compared to young adult tissue preparations. Using the highly sensitive protein dye Deep Purple for the analysis of the 2-D separated muscle proteome and peptide mass fingerprinting for the identification of individual protein spots, a differential expression pattern was observed for contractile proteins, metabolic factors, regulatory components and heat shock elements. A drastic increase was shown for alpha B-crystallin, myosin light chain MLC-1, phosphoglycerate kinase, adenylate kinase, triosephosphate isomerase, albumin, aconitase and nucleoside-diphosphate kinase in aged fibres. In contrast, the expression of pyruvate kinase, aldolase, creatine kinase, transferrin, alpha-tropomyosin and myosin light chain MLC-3 was decreased in old skeletal muscle. Comparative 2-D immunoblotting of selected candidate proteins has confirmed the effect of aging on the skeletal muscle proteome. These findings demonstrate a severely perturbed protein expression pattern in aged skeletal muscle, which reflects the underlying molecular alterations causing a drastic decline of muscle strength in the senescent organism. In the long-term, the systematic deduction of abnormal protein expression

  9. Engineering skeletal myoblasts: roles of three-dimensional culture and electrical stimulation.

    Science.gov (United States)

    Pedrotty, Dawn M; Koh, Jennifer; Davis, Bryce H; Taylor, Doris A; Wolf, Patrick; Niklason, Laura E

    2005-04-01

    Immature skeletal muscle cells, or myoblasts, have been used in cellular cardiomyoplasty in attempts to regenerate cardiac muscle tissue by injection of cells into damaged myocardium. In some studies, muscle tissue within myoblast implant sites may be morphologically similar to cardiac muscle. We hypothesized that identifiable aspects of the cardiac milieu may contribute to growth and development of implanted myoblasts in vivo. To test this hypothesis, we designed a novel in vitro system to mimic some aspects of the electrical and biochemical environment of native myocardium. This system enabled us to separate the three-dimensional (3-D) electrical and biochemical signals that may be involved in myoblast proliferation and plasticity. Myoblasts were grown on 3-D polyglycolic acid mesh scaffolds under control conditions, in the presence of cardiac-like electrical current fluxes, or in the presence of culture medium that had been conditioned by mature cardiomyocytes. Cardiac-like electrical current fluxes caused increased myoblast number in 3-D culture, as determined by DNA assay. The increase in cell number was due to increased cellular proliferation and not differences in apoptosis, as determined by proliferating cell nuclear antigen and TdT-mediated dUTP nick-end labeling. Cardiomyocyte-conditioned medium also significantly increased myoblast proliferation. Expression of transcription factors governing differentiation along skeletal or cardiac lineages was evaluated by immunoblotting. Although these assays are qualitative, no changes in differentiation state along skeletal or cardiac lineages were observed in response to electrical current fluxes. Furthermore, from these experiments, conditioned medium did not appear to alter the differentiation state of skeletal myoblasts. Hence, cardiac milieu appears to stimulate proliferation but does not affect differentiation of skeletal myoblasts.

  10. Evaluation of Pakistani wheat germplasm for bread quality based on allelic variation in HMW glutenin subunits

    International Nuclear Information System (INIS)

    Seventy six Pakistani wheat genotypes including land races were investigated for Bread quality (BQ) based on allelic variation in HMW glutenin subunits at the Glu-1 loci through SDS- polyacrylamide gel electropherosis. Twenty five different allelic combinations were detected with a total of 14 Glu-1 loci. Highest polymorphism was revealed by Glu-B locus and some single/ rare sub units were also screened out. The frequencies of dominant subunits were 50% for 2*, 42.11% for subunit pair 17+18 and 48.68% for 5+10 and 2+12 respectively. The quality scores displayed a range from 4 to 10, however generally good quality score of eight was more frequent (39. 47%). The highest quality scores of 10 and 9 were observed in 22.36% and 19.74% of genotypes respectively. The UPGMA analysis grouped genotypes into three major with two additional sub clusters for each. The cluster 'a' 'b' and 'C' were separated at 73% genetic distance which was further differentiated at a genetic distance of 50% into their sub clusters. Pakistani wheat varieties/land races exhibited large variation in term of HMW-GS. The generated information will lead to the pyrimiding of sub units for high BQ through mission oriented marker assisted breeding programmes for quality improvement of wheat. (author)

  11. Functionally-Impaired HIV-1 Nef Alleles from a Mother-Child Transmission Pair

    Directory of Open Access Journals (Sweden)

    Vincent C. Bond

    2002-10-01

    Full Text Available Abstract: Unusual HIV-1 nef alleles were isolated from a woman and her vertically infected child. Both patients eventually progressed to develop AIDS. The child died at age 6.5 years, while the mother is currently alive, 13 years since her diagnosis with HIV-1. Predicted amino acid sequences of both mother and child Nefs diverged from the HIV-1 clade B consensus. In particular, they exhibited two separate 5-amino acid deletions bracketing a Cterminal dileucine regulatory motif and Trp-Gly mutations at the site for cleavage by the HIV-1 protease. The child’s Nef showed a modest ability to enhance HIV-1 infectivity in MAGI cells, whereas the mother’s Nef did not alter HIV-1 infectivity in the assay. Both Nefs were partially functional for CD4 down-regulation. The child’s Nef was fully functional for MHC-1 down-regulation, while the maternal Nef was non-functional. To our knowledge this study is the first to describe a functional divergence between Nef alleles in a case of mother-to-child HIV-1 transmission.

  12. Six Month Report on Tissue Cultured Avian Skeletal Myofibers in the STL/A Module Aboard STS-77

    Science.gov (United States)

    Vandenburgh, Herman H.

    1997-01-01

    Space travel is know to effect skeletal muscle, causing rapid and pronounced atrophy in humans and animals, even when strenuous exercise is used as a countermeasure. The cellular and molecular bases of this atrophy are unknown. Space travel may cause muscle atrophy by a direct effect on the muscle fibers and/or indirectly by reducing circulating levels of growth factors such as growth hormone. The recent development of a tissue culture incubator system for Shuttle Middeck basic science experiments [Space Tissue Loss (STL) Module] by the Walter Reed Army Institute of Research (WRAIR) allows the study of the effects of space travel directly on isolated skeletal myofibers. Avian bioartificial skeletal muscle 'organoids' containing differentiated skeletal myofibers and connective tissue fibroblasts were flown aboard the Space Shuttle (Space Transportation System, STS) on Flight STS-77, a repeat of a similar experiment flown on STS-66. The results from these two flight experiments show for the first time that space travel has a direct effect on skeletal muscle cells separate from any systemic effects resulting from altered circulating growth factors.

  13. Allelic divergence and cultivar-specific SSR alleles revealed by capillary electrophoresis using fluorescence-labeled SSR markers in sugarcane

    Science.gov (United States)

    Though sugarcane cultivars (Saccharum spp. hybrids) are complex aneu-polyploid hybrids, genetic evaluation and tracking of clone- or cultivar-specific alleles become possible due to capillary electrophoregrams (CE) using fluorescence-labeled SSR primer pairs. Twenty-four sugarcane cultivars, 12 each...

  14. Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis

    DEFF Research Database (Denmark)

    Jacobsen, Soren; Baslund, Bo; Madsen, Hans Ole;

    2002-01-01

    To determine whether variant alleles of the mannose-binding lectin (MBL) gene causing low serum concentrations of MBL and/or polymorphisms of HLA-DRB1 are associated with increased susceptibility to polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) or particular clinical phenotypes of PMR/GCA....

  15. KIR2DL2/2DL3-E35 alleles are functionally stronger than -Q35 alleles

    Science.gov (United States)

    Bari, Rafijul; Thapa, Rajoo; Bao, Ju; Li, Ying; Zheng, Jie; Leung, Wing

    2016-03-01

    KIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is an important factor for donor selection in allogeneic hematopoietic stem cell transplantation, the molecular determinant of functional diversity among various alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at position 35 (E35) are functionally stronger than those with glutamine at the same position (Q35). Cytotoxicity assay showed that NK cells from HLA-C1 positive donors with KIR2DL2/L3-E35 could kill more target cells lacking their ligands than NK cells with the weaker -Q35 alleles, indicating better licensing of KIR2DL2/L3+ NK cells with the stronger alleles. Molecular modeling analysis reveals that the glutamic acid, which is negatively charged, interacts with positively charged histidine located at position 55, thereby stabilizing KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand. The results of this study will be important for future studies of KIR2DL2/L3-associated diseases as well as for donor selection in allogeneic stem cell transplantation.

  16. A new computerised method for the assessment of skeletal maturity in the newborn infant

    Energy Technology Data Exchange (ETDEWEB)

    Argemi, J. [Department of Paediatrics, Consorci Hospitalari Parc Tauli, Barcelona (Spain); Badia, J. [Department of Paediatrics, Consorci Hospitalari Parc Tauli, Barcelona (Spain)

    1997-04-01

    Of the existing methods for assessment of skeletal maturity in children over 1 year of age none is particularly suited to the newborn infant. We describe a computerised method by which area, perimeter and progression in the shape of ossification centres of talus and calcaneus are evaluated separately. From single lateral radiographs of the left ankle of 302 normal term and preterm infants whose birth weights were appropriate for gestational age we constructed reference curves of areas and perimeters at different gestational ages, as well as frequency distributions of each morphological maturity stage. This method may be applicable in assessing skeletal maturity in pathological conditions, such as intrauterine growth retardation and congenital hypothyroidism. (orig.). With 6 figs.

  17. Evaluation of functional erythropoietin receptor status in skeletal muscle in vivo

    DEFF Research Database (Denmark)

    Christensen, Britt; Lundby, Carsten; Jessen, Niels;

    2012-01-01

    myosin light chain 3 and one of desmin/actin were decreased, while three isoforms of creatine kinase and two of glyceraldehyd-3-phosphate dehydrogenase were increased. Conclusions/Significance: Acute exposure to recombinant human erythropoietin is not associated by detectable activation of the Epo-R or......Background: Erythropoietin receptors have been identified in human skeletal muscle tissue, but downstream signal transduction has not been investigated. We therefore studied in vivo effects of systemic erythropoietin exposure in human skeletal muscle. Methodology/Principal Findings: The protocols...... involved 1) acute effects of a single bolus injection of erythropoietin followed by consecutive muscle biopsies for 1-10 hours, and 2) a separate study with prolonged administration for 16 days with biopsies obtained before and after. The presence of erythropoietin receptors in muscle tissue as well as...

  18. Determining skeletal maturation stage using cervical vertebrae: evaluation of three diagnostic methods

    Directory of Open Access Journals (Sweden)

    Luci Mara Fachardo Jaqueira

    2010-12-01

    Full Text Available The aim of the present study was to compare the use of three cervical vertebral evaluation methods (Hassel-Farman, Baccetti et al., and Seedat-Forsberg for determinating skeletal maturation stage in orthodontic patients. Twenty-three radiographs were randomly selected from a private orthodontic practice. Each radiograph was analyzed on three separate occasions by four evaluators (one radiologist and three orthodontists, who determined the skeletal maturation stage using the references established by each of the three methods. Intraevaluator and interevaluator comparisons were performed, and the degree of agreement was established using the weighted Kappa coefficient (95% CI. Good agreement (Kappa between 0.61 and 0.80 was observed between the determinations of most of the evaluators. The three methods demonstrated clinical applicability. However, the method proposed by Baccetti et al. achieved the best results, followed by the Hassel-Farman and the Seedat-Forsberg methods.

  19. Non-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall Stature Accounting for a Carcass Weight QTL (CW-3 and Skeletal Dysplasia in Japanese Black Cattle.

    Directory of Open Access Journals (Sweden)

    Akiko Takasuga

    2015-08-01

    Full Text Available Recessive skeletal dysplasia, characterized by joint- and/or hip bone-enlargement, was mapped within the critical region for a major quantitative trait locus (QTL influencing carcass weight; previously named CW-3 in Japanese Black cattle. The risk allele was on the same chromosome as the Q allele that increases carcass weight. Phenotypic characterization revealed that the risk allele causes disproportional tall stature and bone size that increases carcass weight in heterozygous individuals but causes disproportionately narrow chest width in homozygotes. A non-synonymous variant of FGD3 was identified as a positional candidate quantitative trait nucleotide (QTN and the corresponding mutant protein showed reduced activity as a guanine nucleotide exchange factor for Cdc42. FGD3 is expressed in the growth plate cartilage of femurs from bovine and mouse. Thus, loss of FDG3 activity may lead to subsequent loss of Cdc42 function. This would be consistent with the columnar disorganization of proliferating chondrocytes in chondrocyte-specific inactivated Cdc42 mutant mice. This is the first report showing association of FGD3 with skeletal dysplasia.

  20. Significant associations of stearoyl-CoA desaturase (SCD1 gene with fat deposition and composition in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Zhihua Jiang, Jennifer J. Michal, David J. Tobey, Tyler F. Daniels, Daniel C. Rule, Michael D. MacNeil

    2008-01-01

    Full Text Available Gene expression studies in humans and animals have shown that elevated stearoyl-CoA desaturase (SCD1 activity is associated with increased fat accumulation and monounsaturation of saturated fatty acids in skeletal muscle. However, results of the two reported association studies in humans are inconsistent. In the present study, we annotated the bovine SCD1 gene and identified 3 single nucleotide polymorphisms (SNPs in its 3'untranslated region (UTR. Genotyping these SNPs on a Wagyu x Limousin reference population revealed that the SCD1 gene was significantly associated with six fat deposition and fatty acid composition traits in skeletal muscle, but not with subcutaneous fat depth and percent kidney-pelvic-heart fat. In particular, we confirmed that the high stearoyl-CoA desaturase activities/alleles were positively correlated with beef marbling score, amount of monounsaturated fatty acids and conjugated linoleic acid content, but negatively with amount of saturated fatty acids. The inconsistent associations between human studies might be caused by using different sets of markers because we obeserved that most associated markers are located near the end of 3'UTR. We found that the proximity of the polyadenylation signal site is highly conserved among human, cattle and pig, indicating that the region might contain functional elements involved in posttranscriptional control of SCD1 activity. In conclusion, our cross species study provided solid evidence to support SCD1 gene as a critical player in skeletal muscle fat metabolism.

  1. Comparative Study of Skeletal Stability between Postoperative Skeletal Intermaxillary Fixation and No Skeletal Fixation after Bilateral Sagittal Split Ramus Osteotomy: an 18 Months Retrospective Study

    Directory of Open Access Journals (Sweden)

    Jens Hartlev

    2014-04-01

    Full Text Available Objectives: The purpose of the present study was to evaluate skeletal stability after mandibular advancement with bilateral sagittal split osteotomy. Material and Methods: Twenty-six patients underwent single-jaw bilateral sagittal split osteotomy (BSSO to correct skeletal Class II malocclusion. One group (n = 13 were treated postoperatively with skeletal elastic intermaxillary fixation (IMF while the other group (n = 13 where threated without skeletal elastic IMF. Results: The mean advancement at B-point and Pog in the skeletal elastic IMF group was 6.44 mm and 7.22 mm, respectively. Relapse at follow-up at B-point was -0.74 mm and -0.29 mm at Pog. The mean advancement at B-point and Pog in the no skeletal elastic IMF group was 6.30 mm and 6.45 mm, respectively. Relapse at follow-up at B-point was -0.97 mm and -0.86 mm at Pog. There was no statistical significant (P > 0.05 difference between the skeletal IMF group and the no skeletal group regarding advancement nor relapse at B-point or Pog. Conclusions: Bilateral sagittal split osteotomy is characterized as a stable treatment to correct Class II malocclusion. This study demonstrated no difference of relapse between the skeletal intermaxillary fixation group and the no skeletal intermaxillary fixation group. Because of selection-bias and the reduced number of patients it still remains inconclusive whether to recommend skeletal intermaxillary fixation or not in the prevention of relapse after mandibular advancement.

  2. Maximizing allele detection: Effects of analytical threshold and DNA levels on rates of allele and locus drop-out.

    Science.gov (United States)

    Rakay, Christine A; Bregu, Joli; Grgicak, Catherine M

    2012-12-01

    Interpretation of DNA evidence depends upon the ability of the analyst to accurately compare the DNA profile obtained from an item of evidence and the DNA profile of a standard. This interpretation becomes progressively more difficult as the number of 'drop-out' and 'drop-in' events increase. Analytical thresholds (AT) are typically selected to ensure the false detection of noise is minimized. However, there exists a tradeoff between the erroneous labeling of noise as alleles and the false non-detection of alleles (i.e. drop-out). In this study, the effect ATs had on both types of error was characterized. Various ATs were tested, where three relied upon the analysis of baseline signals obtained from 31 negative samples. The fourth AT was determined by utilizing the relationship between RFU signal and DNA input. The other ATs were the commonly employed 50, 150 and 200 RFU thresholds. Receiver Operating Characteristic (ROC) plots showed that although high ATs completely negated the false labeling of noise, DNA analyzed with ATs derived using analysis of the baseline signal exhibited the lowest rates of drop-out and the lowest total error rates. In another experiment, the effect small changes in ATs had on drop-out was examined. This study showed that as the AT increased from ∼10 to 60 RFU, the number of heterozygous loci exhibiting the loss of one allele increased. Between ATs of 60 and 150 RFU, the frequency of allelic drop-out remained constant at 0.27 (±0.02) and began to decrease when ATs of 150 RFU or greater were utilized. In contrast, the frequency of heterozygous loci exhibiting the loss of both alleles consistently increased with AT. In summary, for samples amplified with less than 0.5ng of DNA, ATs derived from baseline analysis of negatives were shown to decrease the frequency of drop-out by a factor of 100 without significantly increasing rates of erroneous noise detection.

  3. Skeletal scintigraphy in benign and malignant disease

    International Nuclear Information System (INIS)

    This paper begins with a discussion of the technical factors in skeletal scintigraphy, including collimation, the use of three-phase bone scan, and single-photon emission computed tomography. Skeletal scintigraphy for benign conditions is commonly indicated for the patient presenting with pain (trauma, sports-related injury, posttraumatic pain syndrome, painful orthopedic prosthesis) and for the patient with abnormal laboratory test results (metabolic bone disease, Paget disease). For malignant conditions, the bone scan is useful in the evaluation of metastases in patients with extraosseous malignancies and primary bone tumors. The discussion addresses the various scan patterns seen in the more common tumors, such as prostate carcinoma, breast carcinoma, and lung carcinoma. Bone scintigraphy is an exquisitely sensitive modality. With some understanding of the techniques necessary for obtaining the optimal bone scan, and of the patterns that can be seen in various clinical conditions, the radiologist will find the bone scan a very specific tool for evaluating both benign and malignant diseases

  4. YAP-mediated mechanotransduction in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Martina eFischer

    2016-02-01

    Full Text Available Skeletal muscle is not only translating chemical energy into mechanical work, it is also a highly adaptive and regenerative tissue whose architecture and functionality is determined by its mechanical and physical environment. Processing intra- and extracellular mechanical signaling cues contributes to the regulation of cell growth, survival, migration and differentiation. Yes-associated Protein (YAP, a transcriptional coactivator downstream of the Hippo pathway and its paralogue, the transcriptional co-activator with PDZ-binding motif (TAZ, were recently found to play a key role in mechanotransduction in various tissues including skeletal muscle. Furthermore, YAP/TAZ modulate myogenesis and muscle regeneration and abnormal YAP activity has been reported in muscular dystrophy and rhabdomyosarcoma. Here, we summarize the current knowledge of mechanosensing and -signaling in striated muscle. We highlight the role of YAP signaling and discuss the different routes and hypotheses of its regulation in the context of mechanotransduction.

  5. Tractography of peripheral nerves and skeletal muscles.

    Science.gov (United States)

    Khalil, C; Budzik, J F; Kermarrec, E; Balbi, V; Le Thuc, V; Cotten, A

    2010-12-01

    The assessment of human peripheral nerves and skeletal muscles by means of diffusion tensor imaging and tractograpy has been a recent area of research. These techniques have been successfully applied in both volunteers and patients, providing non-invasively, quantitative microstructural parameters (mainly mean fractional anisotropy and apparent diffusion coefficient) and offering a three-dimensional visualization tool of nerves and muscles fibers. DTI and tractography may reveal abnormalities that are beyond the resolution of conventional MR techniques and hence open the way to potential clinical applications. In this article, we will first summarize the current state of DTI and tractography in the evaluation of peripheral nerves and skeletal muscles as well as their potential future clinical applications. Then, we will address important technical considerations, which understanding is necessary to appropriately apply DTI and tractograhy, and in order to understand the current limitations of these innovative and promising techniques. PMID:20392583

  6. Tractography of peripheral nerves and skeletal muscles

    International Nuclear Information System (INIS)

    The assessment of human peripheral nerves and skeletal muscles by means of diffusion tensor imaging and tractograpy has been a recent area of research. These techniques have been successfully applied in both volunteers and patients, providing non-invasively, quantitative microstructural parameters (mainly mean fractional anisotropy and apparent diffusion coefficient) and offering a three-dimensional visualization tool of nerves and muscles fibers. DTI and tractography may reveal abnormalities that are beyond the resolution of conventional MR techniques and hence open the way to potential clinical applications. In this article, we will first summarize the current state of DTI and tractography in the evaluation of peripheral nerves and skeletal muscles as well as their potential future clinical applications. Then, we will address important technical considerations, which understanding is necessary to appropriately apply DTI and tractograhy, and in order to understand the current limitations of these innovative and promising techniques.

  7. Cytokine Signaling in Skeletal Muscle Wasting.

    Science.gov (United States)

    Zhou, Jin; Liu, Bin; Liang, Chun; Li, Yangxin; Song, Yao-Hua

    2016-05-01

    Skeletal muscle wasting occurs in a variety of diseases including diabetes, cancer, Crohn's disease, chronic obstructive pulmonary disease (COPD), disuse, and denervation. Tumor necrosis factor α (TNF-α) is involved in mediating the wasting effect. To date, a causal relationship between TNF-α signaling and muscle wasting has been established in animal models. However, results from clinical trials are conflicting. This is partly due to the fact that other factors such as TNF-like weak inducer of apoptosis (TWEAK) and interleukin 6 (IL-6) are also involved in skeletal muscle wasting. Because muscle wasting is often associated with physical inactivity and reduced food intake, therapeutic interventions will be most effective when multiple approaches are used in conjunction with nutritional support and exercise. PMID:27025788

  8. Epigenetic regulation of skeletal muscle metabolism.

    Science.gov (United States)

    Howlett, Kirsten F; McGee, Sean L

    2016-07-01

    Normal skeletal muscle metabolism is essential for whole body metabolic homoeostasis and disruptions in muscle metabolism are associated with a number of chronic diseases. Transcriptional control of metabolic enzyme expression is a major regulatory mechanism for muscle metabolic processes. Substantial evidence is emerging that highlights the importance of epigenetic mechanisms in this process. This review will examine the importance of epigenetics in the regulation of muscle metabolism, with a particular emphasis on DNA methylation and histone acetylation as epigenetic control points. The emerging cross-talk between metabolism and epigenetics in the context of health and disease will also be examined. The concept of inheritance of skeletal muscle metabolic phenotypes will be discussed, in addition to emerging epigenetic therapies that could be used to alter muscle metabolism in chronic disease states. PMID:27215678

  9. Skeletal manifestations of juvenile hypothyroidism and the impact of treatment on skeletal system

    Directory of Open Access Journals (Sweden)

    Manish Gutch

    2013-01-01

    Full Text Available Thyroid hormone mediates growth and development of the skeleton through its direct effects and through its permissive effects on growth hormone. The effect of hypothyroidism on bone is well described in congenital hypothyroidism, but the impact of thyroid hormone deficiency on a growing skeleton, as it happens with juvenile hypothyroidism, is less defined. In addition, the extent to which the skeletal defects of juvenile hypothyroidism revert on the replacement of thyroid hormone is not known. A study was undertaken in 29 juvenile autoimmune hypothyroid patients to study the skeletal manifestations of juvenile hypothyroidism and the impact of treatment of hypothyroidism on the skeletal system of juvenile patients. Hypothyroidism has a profound impact on the skeletal system and delayed bone age, dwarfism, and thickened bands at the metaphyseal ends being the most common findings. Post treatment, skeletal findings like delayed bone age and dwarfism improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. With the treatment of hypothyroidism, there is an exuberant advancement of bone age, the catch up of bone age being approximately double of the chronological age advancement.

  10. Treatment of Skeletal Muscle Injury: A Review

    OpenAIRE

    Vanden Bossche, L. C.; Vanderstraeten, G; Almqvist, K.F.; Rimbaut, S.; Witvrouw, E.; Philips, N.; Van den Steen, E; Baoge, L

    2012-01-01

    Skeletal muscle injuries are the most common sports-related injuries and present a challenge in primary care and sports medicine. Most types of muscle injuries would follow three stages: the acute inflammatory and degenerative phase, the repair phase and the remodeling phase. Present conservative treatment includes RICE (rest, ice, compression, elevation), nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy. However, if use improper, NSAIDs may suppress an essential inflammator...

  11. Multiple myeloma: imaging evaluation of skeletal disease

    OpenAIRE

    Crichlow, Candice; Sexton, Carlton

    2013-01-01

    This patient is a 56-year-old woman with a history of IGG k multiple myeloma diagnosed 15 years prior to admission. She had widespread lytic bone lesions and pathological fractures, which remarkably had not been accompanied by significant pain, but were mostly refactory to chemotherapy.Keywords: multiple myeloma; skeletal; pathological fracture; imaging(Published: 5 July 2013)Citation: Journal of Community Hospital Internal Medicine Perspectives 2013, 3: 21419 - http://dx.doi.org/10.3402/jchi...

  12. Impaired skeletal muscle microcirculation in systemic sclerosis

    OpenAIRE

    Partovi, Sasan; Schulte, Anja-Carina; Aschwanden, Markus; Staub, Daniel; Benz, Daniela; Imfeld, Stephan; Jacobi, Björn; Broz, Pavel; Jäger, Kurt A; Takes, Martin; Huegli, Rolf W; Bilecen, Deniz; Walker, Ulrich A.

    2012-01-01

    Introduction Muscle symptoms in systemic sclerosis (SSc) may originate from altered skeletal muscle microcirculation, which can be investigated by means of blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI). Methods After ethics committee approval and written consent, 11 consecutive SSc patients (5 men, mean age 52.6 years, mean SSc disease duration 5.4 years) and 12 healthy volunteers (4 men, mean age 45.1 years) were included. Subjects with peripheral arterial occlusi...

  13. Skeletal Muscle Autophagy: A New Metabolic Regulator

    OpenAIRE

    Neel, Brian A.; Lin, Yuxi; Pessin, Jeffrey E.

    2013-01-01

    Autophagy classically functions as a physiological process to degrade cytoplasmic components, protein aggregates, and/or organelles, as a mechanism for nutrient breakdown, and as a regulator of cellular architecture. Proper autophagic flux is vital for both functional skeletal muscle, which controls support and movement of the skeleton, and muscle metabolism. The role of autophagy as a metabolic regulator in muscle has been previously studied; however, the underlying molecular mechanisms that...

  14. Collagen quantification across human skeletal muscles

    OpenAIRE

    Lin, Evie Ya Hui

    2011-01-01

    Intramuscular connective tissue provides structural stability and facilitates force transmission in skeletal muscle. Additionally, it contains extracellular matrix that is crucial for muscle development and regeneration¹. Alterations of collagen content within intramuscular connective tissue have been associated with aging or diseased muscle ²,³. Data of baseline collagen content among different muscles, to provide deeper understanding of normal muscular functions, does not exist. Hence the a...

  15. Pannexin 1 channels in skeletal muscles

    Science.gov (United States)

    Cea, Luis A.; Riquelme, Manuel A.; Vargas, Anibal A.; Urrutia, Carolina; Sáez, Juan C.

    2014-01-01

    Normal myotubes and adult innervated skeletal myofibers express the glycoprotein pannexin1 (Panx1). Six of them form a “gap junction hemichannel-like” structure that connects the cytoplasm with the extracellular space; here they will be called Panx1 channels. These are poorly selective channels permeable to ions, small metabolic substrate, and signaling molecules. So far little is known about the role of Panx1 channels in muscles but skeletal muscles of Panx1−/− mice do not show an evident phenotype. Innervated adult fast and slow skeletal myofibers show Panx1 reactivity in close proximity to dihydropyridine receptors in the sarcolemma of T-tubules. These Panx1 channels are activated by electrical stimulation and extracellular ATP. Panx1 channels play a relevant role in potentiation of muscle contraction because they allow release of ATP and uptake of glucose, two molecules required for this response. In support of this notion, the absence of Panx1 abrogates the potentiation of muscle contraction elicited by repetitive electrical stimulation, which is reversed by exogenously applied ATP. Phosphorylation of Panx1 Thr and Ser residues might be involved in Panx1 channel activation since it is enhanced during potentiation of muscle contraction. Under denervation, Panx1 levels are upregulated and this partially explains the reduction in electrochemical gradient, however its absence does not prevent denervation-induced atrophy but prevents the higher oxidative state. Panx1 also forms functional channels at the cell surface of myotubes and their functional state has been associated with intracellular Ca2+ signals and regulation of myotube plasticity evoked by electrical stimulation. We proposed that Panx1 channels participate as ATP channels and help to keep a normal oxidative state in skeletal muscles. PMID:24782784

  16. Lactate oxidation in human skeletal muscle mitochondria

    DEFF Research Database (Denmark)

    Jacobs, Robert A; Meinild, Anne-Kristine; Nordsborg, Nikolai B;

    2013-01-01

    Lactate is an important intermediate metabolite in human bioenergetics and is oxidized in many different tissues including the heart, brain, kidney, adipose tissue, liver, and skeletal muscle. The mechanism(s) explaining the metabolism of lactate in these tissues, however, remains unclear. Here, we...... chemically permeabilized with saponin, which selectively perforates the sarcolemma and facilitates the loss of cytosolic content without altering mitochondrial membranes, structure, and subcellular interactions. High-resolution respirometry was performed on permeabilized muscle biopsy preparations. By use...

  17. Lip prints: The barcode of skeletal malocclusion

    OpenAIRE

    Pradeep Raghav; Naveen Kumar; Shishir Shingh; N K Ahuja; Priyanka Ghalaut

    2013-01-01

    Introduction: In orthodontics, apart from essential diagnostic aids, there are so many soft tissue analyses in which lips are major part of concern. However, lip prints have never been used in orthodontics as diagnostic aid or forensic tool. Therefore, this study was designed to explore the possible association of lip prints with skeletal malocclusion. Materials and Methods: A sample of 114 subjects in the age group of 18-30 years, from North Indian adult population were selected on the basis...

  18. Ribosome biogenesis during skeletal muscle hypertrophy

    OpenAIRE

    von Walden, Ferdinand

    2014-01-01

    Muscle adaptation to chronic resistance exercise (RE) is the result of a cumulative effect on gene expression and protein content. Following a bout of RE, muscle protein synthesis increases and, if followed by consecutive bouts (training), protein accretion and muscle hypertrophy develops. The protein synthetic capacity of the muscle is dictated by ribosome content. Therefore, the general aim of this thesis is to investigate the regulation of ribosome biogenesis during skeletal muscle hypertr...

  19. Training induced adaptation in horse skeletal muscle

    OpenAIRE

    van Dam, K.G.

    2006-01-01

    It appears that the physiological and biochemical adaptation of skeletal muscle to training in equine species shows a lot of similarities with human and rodent physiological adaptation. On the other hand it is becoming increasingly clear that intra-cellular mechanisms of adaptation (substrate transport, enzyme activity, etc) differ considerably between species. The major drawbacks in equine training physiological research are the lack of an appropriate training model and the lack of control o...

  20. Skeletal muscle HIF-1 and exercise

    OpenAIRE

    Rundqvist, Helene

    2008-01-01

    Regular physical activity prevents and improves a number of disease conditions and reduces the risk for premature death substantially. From a clinical as well as a basic science point of view it is important to create a more fundamental understanding of the molecular mechanisms that contribute to the improved functional capacity induced by regular physical activity. Skeletal muscle tissue exhibits a remarkable ability to adapt to altered demands. Training adaptations include...

  1. A post-transcriptional mechanism regulates calpastatin expression in bovine skeletal muscle.

    Science.gov (United States)

    Nattrass, G S; Cafe, L M; McIntyre, B L; Gardner, G E; McGilchrist, P; Robinson, D L; Wang, Y H; Pethick, D W; Greenwood, P L

    2014-02-01

    The objective of this study was to investigate whether single nucleotide polymorphisms (SNP) in the calpain 1 (CAPN1), calpain 3 (CAPN3) and calpastatin (CAST) genes, which have been shown to be associated with shear force and tenderness differences in the skeletal muscle of cattle, contribute to phenotypic variation in muscle tenderness by modulating the transcriptional activity of their respective gene. The mRNA expression of the calpain and CAST genes was assessed in the longissimus lumborum muscle (LLM) of cattle from two herds located in distinct production zones on the east (New South Wales, NSW) and west (Western Australia, WA) of Australia. The cattle in the herds were mainly Brahman cattle (Bos indicus) with smaller populations of Angus cattle (Bos taurus). There were 191 steers in the WA herd and 107 steers and 106 heifers in the NSW herd. These herds were established by choosing cattle from the diverse population which had different single nucleotide polymorphism (SNP) genotypes at the CAPN1, CAPN3 and CAST loci. Using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the transcriptional activities of the CAPN1 and the CAST genes, but not the CAPN3 gene, were found to differ between favorable, positively associated with tenderness, and unfavorable, negatively associated with tenderness, allelic variants of these genes. These findings suggest that the muscle shear force and consumer taste panel differences in tenderness explained by the CAPN1 and CAST gene markers are a consequence of alterations in their mRNA levels, which may ultimately influence the protein activity of these genes, thereby altering the rate and(or) the extent of postmortem proteolysis in skeletal muscle. Of particular importance were the significantly lower type II and type III CAST 5' splice variant mRNA levels that were detected in the LLM muscle of Brahman and Angus cattle with 2 favourable alleles of the CAST:c.2832A > G polymorphism. Moreover, a reduction in

  2. Modification of an HLA-B PCR-SSOP typing system leading to improved allele determination.

    Science.gov (United States)

    Middleton, D; Williams, F; Cullen, C; Mallon, E

    1995-04-01

    Modifications have been introduced to a previously reported HLA-B PCR-SSOP typing system. This has enabled further definition of alleles, determination of the probe pattern of some alleles not previously examined and identification of patterns of possible new alleles. However there are still some alleles that cannot be differentiated and there are several alleles which when present as a homozygote have the same pattern as in combination with another allele. When the method was applied to the typing of 66 consecutive cadaveric donors there were three donors whose type differed from the serological type.

  3. Allelic frequency distributions of 21 non-combined DNA index system STR loci in a Russian ethnic minority group from Inner Mongolia, China*

    Science.gov (United States)

    Wang, Hong-dan; Shen, Chun-mei; Liu, Wen-juan; Zhang, Yu-dang; Yang, Guang; Yan, Jiang-wei; Qin, Hai-xia; Zhu, Bo-feng

    2013-01-01

    We studied the allelic frequency distributions and statistical forensic parameters of 21 new short tandem repeat (STR) loci and the amelogenin locus, which are not included in the combined DNA index system (CODIS), in a Russian ethnic minority group from the Inner Mongolia Autonomous Region, China. A total of 114 bloodstain samples from unrelated individuals were extracted and co-amplified with four fluorescence-labeled primers in a multiplex polymerase chain reaction (PCR) system. Using capillary electrophoresis, the PCR products of the 21 STR loci were separated and genotyped. A total of 161 alleles were observed in the Russian ethnic minority group, and corresponding allelic frequencies ranged from 0.0044 to 0.5965. The 21 non-CODIS STR loci of the Russian ethnic minority group were characterized by high genetic diversity and therefore may be useful for elucidating the population’s genetic background, for individual identification, and for paternity testing in forensic practice. PMID:23733431

  4. Allelic frequency distributions of 21 non-combined DNA index system STR loci in a Russian ethnic minority group from Inner Mongolia, China.

    Science.gov (United States)

    Wang, Hong-dan; Shen, Chun-mei; Liu, Wen-juan; Zhang, Yu-dang; Yang, Guang; Yan, Jiang-wei; Qin, Hai-xia; Zhu, Bo-feng

    2013-06-01

    We studied the allelic frequency distributions and statistical forensic parameters of 21 new short tandem repeat (STR) loci and the amelogenin locus, which are not included in the combined DNA index system (CODIS), in a Russian ethnic minority group from the Inner Mongolia Autonomous Region, China. A total of 114 bloodstain samples from unrelated individuals were extracted and co-amplified with four fluorescence-labeled primers in a multiplex polymerase chain reaction (PCR) system. Using capillary electrophoresis, the PCR products of the 21 STR loci were separated and genotyped. A total of 161 alleles were observed in the Russian ethnic minority group, and corresponding allelic frequencies ranged from 0.0044 to 0.5965. The 21 non-CODIS STR loci of the Russian ethnic minority group were characterized by high genetic diversity and therefore may be useful for elucidating the population's genetic background, for individual identification, and for paternity testing in forensic practice.

  5. CT findings in skeletal cystic echinococcosis

    International Nuclear Information System (INIS)

    Purpose: To evaluate the CT findings of skeletal cystic echinococcosis. Material and Methods: CT findings of 7 patients with pathologically confirmed skeletal cystic echinococcosis were evaluated. Results: There were 4 men and 3 women, aged 36-75 years. Hydatid cysts were located in the spine (n=2), a rib (n=3), the pelvis and a vertebra (n=1), the pelvis and the left femur (n=1). The size of the lesions varied from 1 cm to 15 cm. CT showed well defined, single or multiple cystic lesions with no contrast enhancement, no calcification, no daughter cysts, and no germinal membrane detachment. The cystic lesion had a honeycomb appearance in 2 cases, there was pathologic fracture in 2 cases, bone expansion in 5 cases, cortical thinning in 6 cases, cortical destruction in 6 cases, bone sclerosis in 1 case, and soft tissue extension in 6 cases. Conclusion: Preoperative differential diagnosis of skeletal cystic lesions should include cystic echinococcosis, especially in endemic areas, since this diagnosis may easily be missed unless kept in mind

  6. Oxidative proteome alterations during skeletal muscle ageing

    Directory of Open Access Journals (Sweden)

    Sofia Lourenço dos Santos

    2015-08-01

    Full Text Available Sarcopenia corresponds to the degenerative loss of skeletal muscle mass, quality, and strength associated with ageing and leads to a progressive impairment of mobility and quality of life. However, the cellular and molecular mechanisms involved in this process are not completely understood. A hallmark of cellular and tissular ageing is the accumulation of oxidatively modified (carbonylated proteins, leading to a decreased quality of the cellular proteome that could directly impact on normal cellular functions. Although increased oxidative stress has been reported during skeletal muscle ageing, the oxidized protein targets, also referred as to the ‘oxi-proteome’ or ‘carbonylome’, have not been characterized yet. To better understand the mechanisms by which these damaged proteins build up and potentially affect muscle function, proteins targeted by these modifications have been identified in human rectus abdominis muscle obtained from young and old healthy donors using a bi-dimensional gel electrophoresis-based proteomic approach coupled with immunodetection of carbonylated proteins. Among evidenced protein spots, 17 were found as increased carbonylated in biopsies from old donors comparing to young counterparts. These proteins are involved in key cellular functions such as cellular morphology and transport, muscle contraction and energy metabolism. Importantly, impairment of these pathways has been described in skeletal muscle during ageing. Functional decline of these proteins due to irreversible oxidation may therefore impact directly on the above-mentioned pathways, hence contributing to the generation of the sarcopenic phenotype.

  7. Redox characterization of functioning skeletal muscle

    Directory of Open Access Journals (Sweden)

    Li eZuo

    2015-11-01

    Full Text Available Skeletal muscle physiology is influenced by the presence of chemically reactive molecules such as reactive oxygen species (ROS. These molecules regulate multiple redox-sensitive signaling pathways that play a critical role in cellular processes including gene expression and protein modification. While ROS have gained much attention for their harmful effects in muscle fatigue and dysfunction, research has also shown ROS to facilitate muscle adaptation after stressors such as physical exercise. This manuscript aims to provide a comprehensive review of the current understanding of redox signaling in skeletal muscle. ROS-induced oxidative stress and its role in the aging process are discussed. Mitochondria have been shown to generate large amounts of ROS during muscular contractions, and thus are susceptible to oxidative stress. ROS can modify proteins located in the mitochondrial membrane leading to cell death and osmotic swelling. ROS also contribute to the necrosis and inflammation of muscle fibers that is associated with muscular diseases including Duchenne muscular dystrophy (DMD. It is imperative that future research continues to investigate the exact role of ROS in normal skeletal muscle function as well as muscular dysfunction and disease.

  8. Perinatal lethal skeletal dysplasia: a case report

    Directory of Open Access Journals (Sweden)

    Sunita Dubey

    2016-01-01

    Full Text Available The word dysplasia originates from ancient Greek words dys (anomalous and plasia (formation. Skeltal dysplasia (SD is a heterogeneous group of congenital anomalies characterized by abnormalities in the development of the bone and cartilage tissue. This results in mark disproportion of the long bones, the spine and fetal head relation to the trunk. Perinatal lethal skeletal dysplasia leads to still birth or early neonatal death due to pulmonary hypoplasia. 30 yrs old G3P3L2 at 32 weeks presented with leaking per vaginum. Her serial scan was done as she had previous stillborn male child with short limbs. Her antenatal scan revealed short limbs from 24 weeks. From18 weeks to 24 weeks she did not underwent any sonography. She went into spontaneous labor and delivered still born male baby with clinical and radiological features suggestive of skeletal dysplasia. Skeletal dysplasia can be diagnosed on antenatal 2 D ultrasound from 14 - 16 weeks onwards. Prenatal genetic testing should be done to diagnose the genetic anomaly and patient should be referred to higher institute for this test. Even if genetic test not done even then termination of pregnancy should be considered based on ultrasound diagnosis especially with family history because of poor fetal prognosis and long term morbidity if survived. [Int J Reprod Contracept Obstet Gynecol 2016; 5(1.000: 224-229

  9. Separation anxiety in children

    Science.gov (United States)

    ... the child experiences anxiety when separated from the primary caregiver (usually the mother). ... Excessive distress when separated from the primary caregiver ... of separation Reluctance to go to sleep without the primary ...

  10. Separation Anxiety (For Parents)

    Science.gov (United States)

    ... 5 Things to Know About Zika & Pregnancy Separation Anxiety KidsHealth > For Parents > Separation Anxiety Print A A ... both of you get through it. How Separation Anxiety Develops Babies adapt pretty well to other caregivers. ...

  11. Fictional Separation Logic

    DEFF Research Database (Denmark)

    Jensen, Jonas Buhrkal; Birkedal, Lars

    2012-01-01

    Separation logic formalizes the idea of local reasoning for heap-manipulating programs via the frame rule and the separating conjunction P * Q, which describes states that can be split into \\emph{separate} parts, with one satisfying P and the other satisfying Q. In standard separation logic...... overlap. We demonstrate, via a range of examples, how fictional separation logic can be used to reason locally and modularly about mutable abstract data types, possibly implemented using sophisticated sharing. Fictional separation logic is defined on top of standard separation logic, and both the meta......, separation means physical separation. In this paper, we introduce \\emph{fictional separation logic}, which includes more general forms of fictional separating conjunctions P * Q, where "*" does not require physical separation, but may also be used in situations where the memory resources described by P and Q...

  12. Analysis of S-RNase alleles of almond (Prunus dulcis): characterization of new sequences, resolution of synonyms and evidence of intragenic recombination.

    Science.gov (United States)

    Ortega, Encarnación; Bosković, Radovan I; Sargent, Daniel J; Tobutt, Kenneth R

    2006-11-01

    Cross-compatibility relationships in almond are controlled by a gametophytically expressed incompatibility system partly mediated by stylar RNases, of which 29 have been reported. To resolve possible synonyms and to provide data for phylogenetic analysis, 21 almond S-RNase alleles were cloned and sequenced from SP (signal peptide region) or C1 (first conserved region) to C5, except for the S29 allele, which could be cloned only from SP to C1. Nineteen sequences (S4, S6, S11-S22, S25-S29)) were potentially new whereas S10 and S24 had previously been published but with different labels. The sequences for S16 and S17 were identical to that for S1, published previously; likewise, S15 was identical to S5. In addition, S4 and S20 were identical, as were S13 and S19. A revised version of the standard table of almond incompatibility genotypes is presented. Several alleles had AT or GA tandem repeats in their introns. Sequences of the 23 distinct newly cloned or already published alleles were aligned. Sliding windows analysis of Ka/Ks identified regions where positive selection may operate; in contrast to the Maloideae, most of the region from the beginning of C3 to the beginning of RC4 appeared not to be under positive selection. Phylogenetic analysis indicated four pairs of alleles had "bootstrap" support > 80%: S5/S10, S4/S8, S11/S24, and S3/S6. Various motifs up to 19 residues long occurred in at least two alleles, and their distributions were consistent with intragenic recombination, as were separate phylogenetic analyses of the 5' and 3' sections. Sequence comparison of phylogenetically related alleles indicated the significance of the region between RC4 and C5 in defining specificity.

  13. Skeletal dysplasias: A radiographic approach and review of common non-lethal skeletal dysplasias

    Institute of Scientific and Technical Information of China (English)

    Ananya; Panda; Shivanand; Gamanagatti; Manisha; Jana; Arun; Kumar; Gupta

    2014-01-01

    Skeletal dysplasias are not uncommon entities and a radiologist is likely to encounter a suspected case of dysplasia in his practice. The correct and early diagnosis of dysplasia is important for management of complications and for future genetic counselling. While there is an exhaustive classification system on dysplasias, it is important to be familiar with the radiological features of common dysplasias. In this article, we enumerate a radiographic approach to skeletal dysplasias, describe the essential as well as differentiating features of common non-lethal skeletal dysplasias and conclude by presenting working algorithms to either definitively diagnose a particular dysplasia or suggest the most likely differential diagnoses to the referring clinician and thus direct further workup of the patient.

  14. Allele-selective inhibition of trinucleotide repeat genes

    OpenAIRE

    Matsui, Masayuki; Corey, David R.

    2012-01-01

    Expanded trinucleotide repeats cause Huntington’s disease (HD) and many other neurodegenerative disorders. There are no cures for these devastating illnesses and treatments are urgently needed. Each trinucleotide repeat disorder is the result of the mutation of just one gene, and agents that block expression of the mutant gene offer a promising option for treatment. Therapies that block expression of both mutant and wild-type alleles can have adverse effects, challenging researchers to develo...

  15. Allele-Specific DNA Methylation Detection by Pyrosequencing®

    DEFF Research Database (Denmark)

    Sommer Kristensen, Lasse; Johansen, Jens Vilstrup; Grønbæk, Kirsten

    2015-01-01

    DNA methylation is an epigenetic modification that plays important roles in healthy as well as diseased cells, by influencing the transcription of genes. In spite the fact that human somatic cells are diploid, most of the currently available methods for the study of DNA methylation do not provide......-effective protocol for allele-specific DNA methylation detection based on Pyrosequencing(®) of methylation-specific PCR (MSP) products including a single nucleotide polymorphism (SNP) within the amplicon....

  16. Multiplex allele-specific target amplification based on PCR suppression

    OpenAIRE

    Broude, Natalia E.; Zhang, Lingang; Woodward, Karen; Englert, David; Cantor, Charles R.

    2001-01-01

    We have developed a strategy for multiplex PCR based on PCR suppression. PCR suppression allows DNA target amplification with only one sequence-specific primer per target and a second primer that is common for all targets. Therefore, an n-plex PCR would require only n + 1 primers. We have demonstrated uniform, efficient amplification of targeted sequences in 14-plex PCR. The high specificity of suppression PCR also provides multiplexed amplification with allele specifi...

  17. Effect of wheat puroindoline alleles on functional properties of starch

    OpenAIRE

    Brites, Carla Moita; Santos, Carla Alexandra Lourenço; Bagulho, Ana Sofia; Beirão-da-Costa, Maria Luisa

    2008-01-01

    Puroindoline a and b (Pina, Pinb) form the molecular basis of bread wheat grain hardness. Varieties with a softer endosperm and a wild genotype, in which both Pina and Pinb were present, seemed to produce less damaged starch Xour than hard varieties, where Pin mutations occurred and changed the starch rheological properties. The functional property of starch samples extracted from wheat varieties with diVerent Pin alleles was evaluated. Starch morphology was characteri...

  18. Generating Novel Allelic Variation Through Activator Insertional Mutagenesis in Maize

    OpenAIRE

    Bai, Ling; Singh, Manjit; Pitt, Lauren; Sweeney, Meredith; Brutnell, Thomas P.

    2007-01-01

    The maize transposable element Activator (Ac) has been exploited as an insertional mutagen to disrupt, clone, and characterize genes in a number of plant species. To develop an Ac-based mutagenesis platform for maize, a large-scale mutagenesis was conducted targeting the pink scutellum1 locus. We selected 1092 Ac transposition events from a closely linked donor Ac, resulting in the recovery of 17 novel ps1 alleles. Multiple phenotypic classes were identified corresponding to Ac insertions in ...

  19. Gene identification and allele-specific marker development for two allelic low phytic acid mutations in rice (Oryza sativa L.)

    International Nuclear Information System (INIS)

    Phytic acid (PA, myo-inositol 1,2,3,4,5,6-hexakisphosphate) is an important anti-nutritional component in cereal and legume grains. PA forms of phosphorus (P) and its salts with micronutrient cations, such as iron and zinc, are indigestible in humans and non-ruminant animals, and hence could affect food/feed nutritional value and cause P pollution of ground water from animal waste. We previously developed a set of low phytic acid (LPA) rice mutants with the aim to increase their nutritional quality. Among them, one line, i.e., Os-lpa -XQZ-1 (hereafter lpa 1-2), was identified to have a mutation allelic to the KBNT lpa 1-1 mutation (hereafter lpa 1-1), which was already delimited to a 47-kb region on chromosome 2. In this study, we searched the candidate gene for these two allelic LPA mutations using T-DNA insertion mutants, mutation detection by CEL I facilitated mismatch cleavage, and gene sequencing. The TIGR locus LOCOs02g57400 was revealed as the candidate gene hosting these two mutations. Sequence analysis showed that the lpa 1-1 is a single base pair substitution mutation, while lpa 1-2 involves a 1,475-bp fragment deletion. A CAPS marker (LPA1CAPS) was developed for distinguishing the lpa 1-1 allele from lpa 1-2 and WT alleles, and InDel marker (LPA1InDel) was developed for differentiating the lpa 1-2 allele from lpa 1-1 and WT ones. Analysis of two populations derived from the two mutants with wild-type varieties confirmed the complete co-segregation of these two markers and LPA phenotype. The LOCOs02g57400 is predicted to encode, through alternative splicing, four possible proteins that are homologous to the 2-phosphoglycerate kinase reported in hyperthermophilic and thermophilic bacteria. The identification of the LPA gene and development of allele-specific markers are of importance not only for breeding LPA varieties, but also for advancing genetics and genomics of phytic acid biosynthesis in rice and other plant species. (author)

  20. Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibres and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609

    DEFF Research Database (Denmark)

    Grunnet, Louise Groth; Brøns, Charlotte; Jacobsen, Stine;

    2009-01-01

    diabetes. Methods. Forty-six young men underwent a hyperinsulinemic euglycemic clamp with excision of skeletal muscle biopsies, an intravenous glucose tolerance test, (31)phosphorous magnetic resonance spectroscopy and 24-hour whole body metabolism was measured in a respiratory chamber. Results. The FTO rs...... significant after correction for body fat percentage. The risk allele was not associated with fat distribution, peripheral insulin sensitivity, insulin secretion, 24-hour energy expenditure or glucose and fat oxidation. The FTO genotype did not influence the mRNA expression of FTO or a set of key nuclear...... or mitochondrially encoded genes in skeletal muscle during rest. Conclusion. Increased energy efficiency - and potentially increased mitochondrial coupling - as suggested by faster recovery rates of PCr and Pi in oxidative muscle fibres may contribute to the increased risk of obesity and type 2 diabetes...

  1. Primary sacrococcygeal chordoma with unusual skeletal muscle metastasis

    Directory of Open Access Journals (Sweden)

    Lisa Vu, MD

    2014-01-01

    Full Text Available Chordomas are rare neoplasms that do not often metastasize. Of the small percent that do metastasize, they very infrequently involve skeletal muscle. Only a few cases of skeletal muscle metastases have been reported in the literature. We report an unusual case of a patient with a primary sacrococcygeal chordoma who experienced a long period of remission but who subsequently developed recurrence and multiple metastatic lesions to skeletal muscles including the deltoid, triceps, and pectineus.

  2. Primary sacrococcygeal chordoma with unusual skeletal muscle metastasis

    Science.gov (United States)

    Vu, Lisa; Haygood, Tamara Miner

    2015-01-01

    Chordomas are rare neoplasms that do not often metastasize. Of the small percent that do metastasize, they very infrequently involve skeletal muscle. Only a few cases of skeletal muscle metastases have been reported in the literature. We report an unusual case of a patient with a primary sacrococcygeal chordoma who experienced a long period of remission but who subsequently developed recurrence and multiple metastatic lesions to skeletal muscles including the deltoid, triceps, and pectineus. PMID:27190554

  3. ORTHOGNATIC SURGICAL TREATMENT OF SKELETAL CLASS III MALOCLUSION: CASE REPORT

    OpenAIRE

    GÜNGÖR, AHMET YALÇIN; Turkkahraman, Hakan; Baykul, Timucin; Aydın, Asım

    2012-01-01

    In this case report a case is presented with skeletal class III malocclusion which were treated with proper planned orthognatic surgery and orthodontic treatment. Our patient was a girl with 16 years, 3 months of chronologic and Ru period of skeletal age. A concave soft tissue profile and Class III molar relation was detected in extraoral and intraoral examination. Cephalometric evaluation revealed a significant Class III skeletal discrepancy (ANBº= -6). Presurgical orthodontics involved deco...

  4. Skeletal muscle regeneration - mechanisms, satellite cells, factors involved

    OpenAIRE

    Marš, Tomaž

    2015-01-01

    Skeletal muscle is the most abundant of the human body's tissues and it represents a substantial percentage of body mass. Its main function is contraction, which produces force for different types of movement. It also includes the contraction of skelet al muscles that enables locomotion, joint stabilization, posture maintenance and production of body heat. Overall, skeletal muscles play an important role in the body's long-term survival and are crucial for fast and efficient response to chang...

  5. Calpain-10 and insulin resistance in human skeletal muscle

    OpenAIRE

    Norton, Luke

    2007-01-01

    Variation in the calpain-10 gene has been linked to a three-fold increased risk for type 2 diabetes in Pima Indian and some European populations. Furthermore, reduced skeletal muscle expression of calpain-10 is associated with reduced insulin mediated glucose disposal and carbohydrate oxidation. The skeletal muscle specific calpain-3 plays a key role in skeletal muscle integrity and has also been linked to insulin resistance in humans and rodents. The major aims of this thesis were to...

  6. A metabolic link to skeletal muscle wasting and regeneration

    OpenAIRE

    René eKoopman; C. Hai eLy; Ryall, James G.

    2014-01-01

    Due to its essential role in movement, insulating the internal organs, generating heat to maintain core body temperature, and acting as a major energy storage depot, any impairment to skeletal muscle structure and function may lead to an increase in both morbidity and mortality. In the context of skeletal muscle, altered metabolism is directly associated with numerous pathologies and disorders, including diabetes, and obesity, while many skeletal muscle pathologies have secondary changes in m...

  7. Skeletal muscle adaptation in response to exercise(Ⅰ)

    Institute of Scientific and Technical Information of China (English)

    Ping Li; Zhen Yan

    2004-01-01

    @@ INTRODUCTION Skeletal muscles of adult mammalian species, including humans,are the source of power for locomotion and other daily activities essential for survival. Loss of skeletal musclecontractile function is a major cause of falling,morbidity and mortality,especially in elderly populations [1]. More importantly,skeletal muscles collectively influence total body metabolism of glucose, fat and protein, abnormalities of which are associated with a variety of common diseases[2-3].

  8. Working around the clock: circadian rhythms and skeletal muscle

    OpenAIRE

    ZHANG, XIPING; Dube, Thomas J.; Esser, Karyn A.

    2009-01-01

    The study of the circadian molecular clock in skeletal muscle is in the very early stages. Initial research has demonstrated the presence of the molecular clock in skeletal muscle and that skeletal muscle of a clock-compromised mouse, Clock mutant, exhibits significant disruption in normal expression of many genes required for adult muscle structure and metabolism. In light of the growing association between the molecular clock, metabolism, and metabolic disease, it will also be important to ...

  9. Regulatory mechanisms of skeletal muscle protein turnover during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    2009-01-01

    Skeletal muscle protein turnover is a relatively slow metabolic process that is altered by various physiological stimuli such as feeding/fasting and exercise. During exercise, catabolism of amino acids contributes very little to ATP turnover in working muscle. With regards to protein turnover...... with available and new techniques will undoubtedly reveal the functional significance and signaling mechanisms behind changes in skeletal muscle protein turnover during exercise. Key words: Exercise, skeletal muscle, protein metabolism, translation....

  10. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

    OpenAIRE

    McCarthy, John J.; Mula, Jyothi; Miyazaki, Mitsunori; Erfani, Rod; Garrison, Kelcye; Farooqui, Amreen B.; Srikuea, Ratchakrit; Lawson, Benjamin A.; Grimes, Barry; Keller, Charles; Zant, Gary Van; Campbell, Kenneth S.; Esser, Karyn A.; Dupont-Versteegden, Esther E.; Peterson, Charlotte A.

    2011-01-01

    An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overl...

  11. Na,K-ATPase regulation in skeletal muscle.

    Science.gov (United States)

    Pirkmajer, Sergej; Chibalin, Alexander V

    2016-07-01

    Skeletal muscle contains one of the largest and the most dynamic pools of Na,K-ATPase (NKA) in the body. Under resting conditions, NKA in skeletal muscle operates at only a fraction of maximal pumping capacity, but it can be markedly activated when demands for ion transport increase, such as during exercise or following food intake. Given the size, capacity, and dynamic range of the NKA pool in skeletal muscle, its tight regulation is essential to maintain whole body homeostasis as well as muscle function. To reconcile functional needs of systemic homeostasis with those of skeletal muscle, NKA is regulated in a coordinated manner by extrinsic stimuli, such as hormones and nerve-derived factors, as well as by local stimuli arising in skeletal muscle fibers, such as contractions and muscle energy status. These stimuli regulate NKA acutely by controlling its enzymatic activity and/or its distribution between the plasma membrane and the intracellular storage compartment. They also regulate NKA chronically by controlling NKA gene expression, thus determining total NKA content in skeletal muscle and its maximal pumping capacity. This review focuses on molecular mechanisms that underlie regulation of NKA in skeletal muscle by major extrinsic and local stimuli. Special emphasis is given to stimuli and mechanisms linking regulation of NKA and energy metabolism in skeletal muscle, such as insulin and the energy-sensing AMP-activated protein kinase. Finally, the recently uncovered roles for glutathionylation, nitric oxide, and extracellular K(+) in the regulation of NKA in skeletal muscle are highlighted. PMID:27166285

  12. Cryopreservation of human skeletal muscle impairs mitochondrial function

    DEFF Research Database (Denmark)

    Larsen, Steen; Wright-Paradis, C; Gnaiger, E;

    2012-01-01

    Previous studies have investigated if cryopreservation is a viable approach for functional mitochondrial analysis. Different tissues have been studied, and conflicting results have been published. The aim of the present study was to investigate if mitochondria in human skeletal muscle maintain...... functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity...... loss from the mitochondria. The results from this study demonstrate that normal mitochondrial functionality is not maintained in cryopreserved human skeletal muscle samples....

  13. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

    2011-01-01

    The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...... the role of skeletal muscle transverse tubules as potential modulators of tissue insulin responsiveness....

  14. Power of IRT in GWAS: successful QTL mapping of sum score phenotypes depends on interplay between risk allele frequency, variance explained by the risk allele, and test characteristics.

    Science.gov (United States)

    van den Berg, Stéphanie M; Service, Susan K

    2012-12-01

    As data from sequencing studies in humans accumulate, rare genetic variants influencing liability to disease and disorders are expected to be identified. Three simulation studies show that characteristics and properties of diagnostic instruments interact with risk allele frequency to affect the power to detect a quantitative trait locus (QTL) based on a test score derived from symptom counts or questionnaire items. Clinical tests, that is, tests that show a positively skewed phenotypic sum score distribution in the general population, are optimal to find rare risk alleles of large effect. Tests that show a negatively skewed sum score distribution are optimal to find rare protective alleles of large effect. For alleles of small effect, tests with normally distributed item parameters give best power for a wide range of allele frequencies. The item-response theory framework can help understand why an existing measurement instrument has more power to detect risk alleles with either low or high frequency, or both kinds.

  15. Novel method for analysis of allele specific expression in triploid Oryzias latipes reveals consistent pattern of allele exclusion.

    Directory of Open Access Journals (Sweden)

    Tzintzuni I Garcia

    Full Text Available Assessing allele-specific gene expression (ASE on a large scale continues to be a technically challenging problem. Certain biological phenomena, such as X chromosome inactivation and parental imprinting, affect ASE most drastically by completely shutting down the expression of a whole set of alleles. Other more subtle effects on ASE are likely to be much more complex and dependent on the genetic environment and are perhaps more important to understand since they may be responsible for a significant amount of biological diversity. Tools to assess ASE in a diploid biological system are becoming more reliable. Non-diploid systems are, however, not uncommon. In humans full or partial polyploid states are regularly found in both healthy (meiotic cells, polynucleated cell types and diseased tissues (trisomies, non-disjunction events, cancerous tissues. In this work we have studied ASE in the medaka fish model system. We have developed a method for determining ASE in polyploid organisms from RNAseq data and we have implemented this method in a software tool set. As a biological model system we have used nuclear transplantation to experimentally produce artificial triploid medaka composed of three different haplomes. We measured ASE in RNA isolated from the livers of two adult, triploid medaka fish that showed a high degree of similarity. The majority of genes examined (82% shared expression more or less evenly among the three alleles in both triploids. The rest of the genes (18% displayed a wide range of ASE levels. Interestingly the majority of genes (78% displayed generally consistent ASE levels in both triploid individuals. A large contingent of these genes had the same allele entirely suppressed in both triploids. When viewed in a chromosomal context, it is revealed that these genes are from large sections of 4 chromosomes and may be indicative of some broad scale suppression of gene expression.

  16. Skeletal Stability after Large Mandibular Advancement (> 10 mm with Bilateral Sagittal Split Osteotomy and Skeletal Elastic Intermaxillary Fixation

    Directory of Open Access Journals (Sweden)

    Kristoffer Schwartz

    2016-06-01

    Full Text Available Objectives: The aim of the present study was to assess the skeletal stability after large mandibular advancement (> 10 mm with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation and to correlate the skeletal stability with the vertical facial type. Material and Methods: A total of 33 consecutive patients underwent bimaxillary surgery to correct skeletal Class II malocclusion with a mandibular advancement (> 10 mm measured at B-point and postoperative skeletal elastic intermaxillary fixation for 16 weeks. Skeletal stability was evaluated using lateral cephalometric radiographs obtained preoperative (T1, 8 weeks postoperatively (T2, and 18 month postoperatively (T3. B-point and pogonion (Pog was used to measure the skeletal relapse and the mandibular plane angle (MP-angle was used to determine the vertical facial type. Results: The mean advancement from T1 to T2 were 11.6 mm and 13.5 mm at B-point and Pog, respectively. The mean skeletal relapse from T2 to T3 was -1.3 mm at B-point and -1.6 mm at Pog. The nineteen patients characterized as long facial types, showed the highest amount of skeletal relapse (-1.5 mm at B-point and -1.9 mm at Pog. Conclusions: The present study showed a limited amount of skeletal relapse in large mandibular advancement (> 10 mm with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation. Bilateral sagittal split osteotomy in combination with skeletal intermaxillary fixation can therefore be an alternative to distraction osteogenesis in large mandibular advancements.

  17. Skeletal Stability after Large Mandibular Advancement (> 10 mm) with Bilateral Sagittal Split Osteotomy and Skeletal Elastic Intermaxillary Fixation

    Science.gov (United States)

    Rodrigo-Domingo, Maria; Jensen, Thomas

    2016-01-01

    ABSTRACT Objectives The aim of the present study was to assess the skeletal stability after large mandibular advancement (> 10 mm) with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation and to correlate the skeletal stability with the vertical facial type. Material and Methods A total of 33 consecutive patients underwent bimaxillary surgery to correct skeletal Class II malocclusion with a mandibular advancement (> 10 mm) measured at B-point and postoperative skeletal elastic intermaxillary fixation for 16 weeks. Skeletal stability was evaluated using lateral cephalometric radiographs obtained preoperative (T1), 8 weeks postoperatively (T2), and 18 month postoperatively (T3). B-point and pogonion (Pog) was used to measure the skeletal relapse and the mandibular plane angle (MP-angle) was used to determine the vertical facial type. Results The mean advancement from T1 to T2 were 11.6 mm and 13.5 mm at B-point and Pog, respectively. The mean skeletal relapse from T2 to T3 was -1.3 mm at B-point and -1.6 mm at Pog. The nineteen patients characterized as long facial types, showed the highest amount of skeletal relapse (-1.5 mm at B-point and -1.9 mm at Pog). Conclusions The present study showed a limited amount of skeletal relapse in large mandibular advancement (> 10 mm) with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation. Bilateral sagittal split osteotomy in combination with skeletal intermaxillary fixation can therefore be an alternative to distraction osteogenesis in large mandibular advancements. PMID:27489609

  18. A high-throughput method for genotyping S-RNase alleles in apple

    DEFF Research Database (Denmark)

    Larsen, Bjarne; Ørgaard, Marian; Toldam-Andersen, Torben Bo;

    2016-01-01

    We present a new efficient screening tool for detection of S-alleles in apple. The protocol using general and multiplexed primers for PCR reaction and fragment detection on an automatized capillary DNA sequencer exposed a higher number of alleles than any previous studies. Analysis of alleles...

  19. Improvement of livestock breeding strategies using physiologic and functional genomic information of the muscle regulatory factors gene family for skeletal muscle development

    NARCIS (Netherlands)

    Pas, te M.F.W.; Soumillon, A.

    2001-01-01

    A defined number of skeletal muscle fibers are formed in two separate waves during prenatal development, while postnatal growth is restricted to hypertrophic muscle fiber growth. The genes of the MRF (muscle regulatory factors) gene family, consisting of 4 structurally related transcription factors

  20. PLASTICITY OF SKELETAL MUSCLE STUDIED BY STEREOLOGY

    Directory of Open Access Journals (Sweden)

    Ida Eržen

    2011-05-01

    Full Text Available The present contribution provides an overview of stereological methods applied in the skeletal muscle research at the Institute of Anatomy of the Medical Faculty in Ljubljana. Interested in skeletal muscle plasticity we studied three different topics: (i expression of myosin heavy chain isoforms in slow and fast muscles under experimental conditions, (ii frequency of satellite cells in young and old human and rat muscles and (iii capillary supply of rat fast and slow muscles. We analysed the expression of myosin heavy chain isoforms within slow rat soleus and fast extensor digitorum longus muscles after (i homotopic and heterotopic transplantation of both muscles, (ii low frequency electrical stimulation of the fast muscle and (iii transposition of the fast nerve to the slow muscle. The models applied were able to turn the fast muscle into a completely slow muscle, but not vice versa. One of the indicators for the regenerative potential of skeletal muscles is its satellite cell pool. The estimated parameters, number of satellite cells per unit fibre length, corrected to the reference sarcomere length (Nsc/Lfib and number of satellite cells per number of nuclei (myonuclei and satellite cell nuclei (Nsc/Nnucl indicated that the frequency of M-cadherin stained satellite cells declines in healthy old human and rat muscles compared to young muscles. To access differences in capillary densities among slow and fast muscles and slow and fast muscle fibres, we have introduced Slicer and Fakir methods, and tested them on predominantly slow and fast rat muscles. Discussing three different topics that require different approach, the present paper reflects the three decades of the development of stereological methods: 2D analysis by simple point counting in the 70's, the disector in the 80's and virtual spatial probes in the 90's. In all methods the interactive computer assisted approach was utilised.

  1. Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes

    Directory of Open Access Journals (Sweden)

    Stringer Saundra L

    2006-10-01

    Full Text Available Abstract Background Loss of heterozygosity (LOH contributes to many cancers, but the rate at which these events occur in normal cells of the body is not clear. LOH would be detectable in diverse cell types in the body if this event were to confer an obvious cellular phenotype. Mice that carry two different fluorescent protein genes as alleles of a locus would seem to be a useful tool for addressing this issue because LOH would change a cell's phenotype from dichromatic to monochromatic. In addition, LOH caused by mitotic crossing over might be discernable in tissues because this event produces a pair of neighboring monochromatic cells that are different colors. Results As a step in assessing the utility of this approach, we derived primary embryonic fibroblast populations and embryonic stem cell lines from mice that carried two different fluorescent protein genes as alleles at the chromosome 6 locus, ROSA26. Fluorescence activated cell sorting (FACS showed that the vast majority of cells in each line expressed the two marker proteins at similar levels, and that populations exhibited expression noise similar to that seen in bacteria and yeast. Cells with a monochromatic phenotype were present at frequencies on the order of 10-4 and appeared to be produced at a rate of approximately 10-5 variant cells per mitosis. 45 of 45 stably monochromatic ES cell clones exhibited loss of the expected allele at the ROSA26 locus. More than half of these clones retained heterozygosity at a locus between ROSA26 and the centromere. Other clones exhibited LOH near the centromere, but were disomic for chromosome 6. Conclusion Allelic fluorescent markers allowed LOH at the ROSA26 locus to be detected by FACS. LOH at this locus was usually not accompanied by LOH near the centromere, suggesting that mitotic recombination was the major cause of ROSA26 LOH. Dichromatic mouse embryonic cells provide a novel system for studying genetic/karyotypic stability and factors

  2. Regulation of skeletal muscle cell plasticity by the peroxisome proliferator-activated receptor gamma coactivator 1alpha

    OpenAIRE

    Handschin, C.

    2010-01-01

    Exercise triggers a pleiotropic response in skeletal muscle, which results in a profound remodeling of this tissue. Physical activity-dependent muscle fiber plasticity is regulated by a number of distinct signaling pathways. Even though most of these pathways are activated by different stimuli and in a temporally and spatially separated manner during exercise, many of the major signal transduction events converge on the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-...

  3. Skeletal muscle metastasis from uterine leiomyosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    O' Brien, J.M.; Brennan, D.D.; Taylor, D.H.; Eustace, S.J. [Cappagh National Orthopaedic Hospital, Department of Radiology, Dublin (Ireland); Holloway, D.P.; O' Keane, J.C. [Cappagh National Orthopaedic Hospital, Department of Pathology, Dublin (Ireland); Hurson, B. [Cappagh National Orthopaedic Hospital, Department of Orthopaedics, Dublin (Ireland)

    2004-11-01

    A case of a 68-year-old woman who presented with a rapidly enlarging painful right thigh mass is presented. She had a known diagnosis of uterine leiomyosarcoma following a hysterectomy for dysfunctional uterine bleeding. She subsequently developed a single hepatic metastatic deposit that responded well to radiofrequency ablation. Whole-body MRI and MRA revealed a vascular mass in the sartorius muscle and a smaller adjacent mass in the gracilis muscle, proven to represent metastatic leiomyosarcoma of uterine origin. To our knowledge, metastatic uterine leiomyosarcoma to the skeletal muscle has not been described previously in the English medical literature. (orig.)

  4. Skeletal muscle metastasis from uterine leiomyosarcoma.

    Science.gov (United States)

    O'Brien, J M; Brennan, D D; Taylor, D H; Holloway, D P; Hurson, B; O'Keane, J C; Eustace, S J

    2004-11-01

    A case of a 68-year-old woman who presented with a rapidly enlarging painful right thigh mass is presented. She had a known diagnosis of uterine leiomyosarcoma following a hysterectomy for dysfunctional uterine bleeding. She subsequently developed a single hepatic metastatic deposit that responded well to radiofrequency ablation. Whole-body MRI and MRA revealed a vascular mass in the sartorius muscle and a smaller adjacent mass in the gracilis muscle, proven to represent metastatic leiomyosarcoma of uterine origin. To our knowledge, metastatic uterine leiomyosarcoma to the skeletal muscle has not been described previously in the English medical literature.

  5. Human Skeletal Muscle Health with Spaceflight

    Science.gov (United States)

    Trappe, Scott

    2012-07-01

    This lecture will overview the most recent aerobic and resistance exercise programs used by crewmembers while aboard the International Space Station (ISS) for six months and examine its effectiveness for protecting skeletal muscle health. Detailed information on the exercise prescription program, whole muscle size, whole muscle performance, and cellular data obtained from muscle biopsy samples will be presented. Historically, detailed information on the exercise program while in space has not been available. These most recent exercise and muscle physiology findings provide a critical foundation to guide the exercise countermeasure program forward for future long-duration space missions.

  6. Converting skeletal structures to quad dominant meshes

    DEFF Research Database (Denmark)

    Bærentzen, Jakob Andreas; Misztal, Marek Krzysztof; Welnicka, Katarzyna

    2012-01-01

    We propose the Skeleton to Quad-dominant polygonal Mesh algorithm (SQM), which converts skeletal structures to meshes composed entirely of polar and annular regions. Both types of regions have a regular structure where all faces are quads except for a single ring of triangles at the center of each...... polar region. The algorithm produces high quality meshes which contain irregular vertices only at the poles or where several regions join. It is trivial to produce a stripe parametrization for the output meshes which also lend themselves well to polar subdivision. After an initial description of SQM, we...

  7. Contemporary approaches for imaging skeletal metastasis

    Institute of Scientific and Technical Information of China (English)

    David Ulmert; Lilja Solnes; Daniel LJ Thorek

    2015-01-01

    The skeleton is a common site of cancer metastasis. Notably high incidences of bone lesions are found for breast, prostate, and renal carcinoma. Malignant bone tumors result in significant patient morbidity. Identification of these lesions is a critical step to accurately stratify patients, guide treatment course, monitor disease progression, and evaluate response to therapy. Diagnosis of cancer in the skeleton typically relies on indirect bone-targeted radiotracer uptake at sites of active bone remodeling. In this manuscript, we discuss established and emerging tools and techniques for detection of bone lesions, quantification of skeletal tumor burden, and current clinical challenges.

  8. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent

    OpenAIRE

    Jeppesen, J; Albers, P. H.; Rose, A. J.; Birk, J. B.; Schjerling, P; Dzamko, N.; Steinberg, G. R.; Kiens, B

    2011-01-01

    The aim of this study was to investigate the molecular mechanisms regulating FA translocase CD36 (FAT/CD36) translocation and FA uptake in skeletal muscle during contractions. In one model, wild-type (WT) and AMP-dependent protein kinase kinase dead (AMPK KD) mice were exercised or extensor digitorum longus (EDL) and soleus (SOL) muscles were contracted, ex vivo. In separate studies, FAT/CD36 translocation and FA uptake in response to muscle contractions were investigated in the perfused rat ...

  9. Nosology and classification of genetic skeletal disorders: 2015 revision.

    Science.gov (United States)

    Bonafe, Luisa; Cormier-Daire, Valerie; Hall, Christine; Lachman, Ralph; Mortier, Geert; Mundlos, Stefan; Nishimura, Gen; Sangiorgi, Luca; Savarirayan, Ravi; Sillence, David; Spranger, Jürgen; Superti-Furga, Andrea; Warman, Matthew; Unger, Sheila

    2015-12-01

    The purpose of the nosology is to serve as a "master" list of the genetic disorders of the skeleton to facilitate diagnosis and to help delineate variant or newly recognized conditions. This is the 9th edition of the nosology and in comparison with its predecessor there are fewer conditions but many new genes. In previous editions, diagnoses that were phenotypically indistinguishable but genetically heterogenous were listed separately but we felt this was an unnecessary distinction. Thus the overall number of disorders has decreased from 456 to 436 but the number of groups has increased to 42 and the number of genes to 364. The nosology may become increasingly important today and tomorrow in the era of big data when the question for the geneticist is often whether a mutation identified by next generation sequencing technology in a particular gene can explain the clinical and radiological phenotype of their patient. This can be particularly difficult to answer conclusively in the prenatal setting. Personalized medicine emphasizes the importance of tailoring diagnosis and therapy to the individual but for our patients with rare skeletal disorders, the importance of tapping into a resource where genetic data can be centralized and made available should not be forgotten or underestimated. The nosology can also serve as a reference for the creation of locus-specific databases that are expected to help in delineating genotype-phenotype correlations and to harbor the information that will be gained by combining clinical observations and next generation sequencing results.

  10. A simplified immunohistochemical classification of skeletal muscle fibres in mouse

    Directory of Open Access Journals (Sweden)

    M. Kammoun

    2014-06-01

    Full Text Available The classification of muscle fibres is of particular interest for the study of the skeletal muscle properties in a wide range of scientific fields, especially animal phenotyping. It is therefore important to define a reliable method for classifying fibre types. The aim of this study was to establish a simplified method for the immunohistochemical classification of fibres in mouse. To carry it out, we first tested a combination of several anti myosin heavy chain (MyHC antibodies in order to choose a minimum number of antibodies to implement a semi-automatic classification. Then, we compared the classification of fibres to the MyHC electrophoretic pattern on the same samples. Only two anti MyHC antibodies on serial sections with the fluorescent labeling of the Laminin were necessary to classify properly fibre types in Tibialis Anterior and Soleus mouse muscles in normal physiological conditions. This classification was virtually identical to the classification realized by the electrophoretic separation of MyHC. This immunohistochemical classification can be applied to the total area of Tibialis Anterior and Soleus mouse muscles. Thus, we provide here a useful, simple and time-efficient method for immunohistochemical classification of fibres, applicable for research in mouse

  11. Autoimmune disease classification by inverse association with SNP alleles.

    Directory of Open Access Journals (Sweden)

    Marina Sirota

    2009-12-01

    Full Text Available With multiple genome-wide association studies (GWAS performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorporate the direction of allele-specific disease associations for SNPs. In this work, we refine the notion of a genetic variation profile for a given disease to capture strength of association with multiple SNPs in an allele-specific fashion. We apply this method to compare genetic variation profiles of six autoimmune diseases: multiple sclerosis (MS, ankylosing spondylitis (AS, autoimmune thyroid disease (ATD, rheumatoid arthritis (RA, Crohn's disease (CD, and type 1 diabetes (T1D, as well as five non-autoimmune diseases. We quantify pair-wise relationships between these diseases and find two broad clusters of autoimmune disease where SNPs that make an individual susceptible to one class of autoimmune disease also protect from diseases in the other autoimmune class. We find that RA and AS form one such class, and MS and ATD another. We identify specific SNPs and genes with opposite risk profiles for these two classes. We furthermore explore individual SNPs that play an important role in defining similarities and differences between disease pairs. We present a novel, systematic, cross-platform approach to identify allele-specific relationships between disease pairs based on genetic variation as well as the individual SNPs which drive the relationships. While recognizing similarities between diseases might lead to identifying novel treatment options, detecting differences between diseases previously thought to be similar may point to key novel disease-specific genes and pathways.

  12. Modulation of allele leakiness and adaptive mutability in Escherichia coli

    Indian Academy of Sciences (India)

    R. Jayaraman

    2000-08-01

    It is shown that partial phenotypic suppression of two ochre mutations (argE3 and lacZU118) and an amber mutation (in argE) by sublethal concentrations of streptomycin in an rpsL+ (streptomycin-sensitive) derivative of the Escherichia coli strain AB1157 greatly enhances their adaptive mutability under selection. Streptomycin also increases adaptive mutability brought about by the ppm mutation described earlier. Inactivation of recA affects neither phenotypic suppression by streptomycin nor replication-associated mutagenesis but abolishes adaptive mutagenesis. These results indicate a causal relationship between allele leakiness and adaptive mutability.

  13. Allelic drop-out probabilities estimated by logistic regression

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Asplund, Maria;

    2012-01-01

    We discuss the model for estimating drop-out probabilities presented by Tvedebrink et al. [7] and the concerns, that have been raised. The criticism of the model has demonstrated that the model is not perfect. However, the model is very useful for advanced forensic genetic work, where allelic drop......-out is occurring. With this discussion, we hope to improve the drop-out model, so that it can be used for practical forensic genetics and stimulate further discussions. We discuss how to estimate drop-out probabilities when using a varying number of PCR cycles and other experimental conditions....

  14. Isotope separation principles

    Energy Technology Data Exchange (ETDEWEB)

    Benedict, Manson

    1963-03-15

    Isotope separation theory of ideal cascades is discussed. It is shown how the most important characteristics of an isotope separation process can be worked out from the compositions and flow rates of the feed and product streams. These characteristics include plant size, dependence of product rate on product purity, minimum power consumption, costs of isotope separation, minimum time for reaching steady production, and effect of third component on process performance and product costs. The concepts of value functions, separative power, and separative work are used to derive the characteristics, and the analogy between isotope separation theory and thermodynamics is emphasized. (D.L.C.)

  15. Skeletal Structure of Printed Words: Evidence From the Stroop Task

    Science.gov (United States)

    Berent, Iris; Marom, Michal

    2005-01-01

    Do readers encode the sequencing of consonant (C) and vowel (V) phonemes (skeletal structure) in printed words? The authors used the Stroop task to examine readers' sensitivity to skeletal structure. In Experiment 1, CVC nonwords (e.g., pof) facilitated the naming of colors with congruent frames (e.g., red, a CVC word) but not with incongruent…

  16. A unified anatomy ontology of the vertebrate skeletal system.

    Directory of Open Access Journals (Sweden)

    Wasila M Dahdul

    Full Text Available The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO, to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish and multispecies (teleost, amphibian vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages, and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO, Gene Ontology (GO, Uberon, and Cell Ontology (CL, and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

  17. A unified anatomy ontology of the vertebrate skeletal system.

    Science.gov (United States)

    Dahdul, Wasila M; Balhoff, James P; Blackburn, David C; Diehl, Alexander D; Haendel, Melissa A; Hall, Brian K; Lapp, Hilmar; Lundberg, John G; Mungall, Christopher J; Ringwald, Martin; Segerdell, Erik; Van Slyke, Ceri E; Vickaryous, Matthew K; Westerfield, Monte; Mabee, Paula M

    2012-01-01

    The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

  18. Current opportunities and challenges in skeletal muscle tissue engineering

    NARCIS (Netherlands)

    Koning, Merel; Harmsen, Martin C; van Luyn, Marja J A; Werker, Paul M N

    2009-01-01

    The purpose of this article is to give a concise review of the current state of the art in tissue engineering (TE) of skeletal muscle and the opportunities and challenges for future clinical applicability. The endogenous progenitor cells of skeletal muscle, i.e. satellite cells, show a high pronenes

  19. Cryopreservation of human skeletal muscle impairs mitochondrial function

    DEFF Research Database (Denmark)

    Larsen, S; Wright-Paradis, C; Gnaiger, E;

    2012-01-01

    functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity of...

  20. Skeletal muscle stem cells from animals I. Basic cell biology

    Science.gov (United States)

    Skeletal muscle stem cells from food-producing animals have been of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding...

  1. Chance findings in skeletal radiology; Zufallsbefunde in der Skelettradiologie

    Energy Technology Data Exchange (ETDEWEB)

    Freyschmidt, Juergen [Beratungsstelle und Referenzzentrum fuer Osteoradiologie, Bremen (Germany)

    2016-08-01

    The book on chance findings in skeletal radiology covers the following issues: Part (I): Introduction - what are chance findings? Part (II); change findings under different radiological modalities: most frequent skeletal radiological change findings: scintiscanning, radiography and CT, MRT, PET and PET/CT. Part (III): case studies: skull; spinal cord; shoulder/pectoral girdle, chest; pelvis and hip joints; upper extremities; lower extremities.

  2. Glucose transporter expression in human skeletal muscle fibers

    DEFF Research Database (Denmark)

    Gaster, M; Handberg, A; Beck-Nielsen, H;

    2000-01-01

    amplification (TSA) technique to detect the localization of glucose transporter expression in human skeletal muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in human skeletal muscle cells during gestation...

  3. Skeletal Muscle Mitochondria and Aging: A Review

    Directory of Open Access Journals (Sweden)

    Courtney M. Peterson

    2012-01-01

    Full Text Available Aging is characterized by a progressive loss of muscle mass and muscle strength. Declines in skeletal muscle mitochondria are thought to play a primary role in this process. Mitochondria are the major producers of reactive oxygen species, which damage DNA, proteins, and lipids if not rapidly quenched. Animal and human studies typically show that skeletal muscle mitochondria are altered with aging, including increased mutations in mitochondrial DNA, decreased activity of some mitochondrial enzymes, altered respiration with reduced maximal capacity at least in sedentary individuals, and reduced total mitochondrial content with increased morphological changes. However, there has been much controversy over measurements of mitochondrial energy production, which may largely be explained by differences in approach and by whether physical activity is controlled for. These changes may in turn alter mitochondrial dynamics, such as fusion and fission rates, and mitochondrially induced apoptosis, which may also lead to net muscle fiber loss and age-related sarcopenia. Fortunately, strategies such as exercise and caloric restriction that reduce oxidative damage also improve mitochondrial function. While these strategies may not completely prevent the primary effects of aging, they may help to attenuate the rate of decline.

  4. Phosphoproteomic analysis of aged skeletal muscle.

    Science.gov (United States)

    Gannon, Joan; Staunton, Lisa; O'Connell, Kathleen; Doran, Philip; Ohlendieck, Kay

    2008-07-01

    One of the most important post-translational modifications is represented by phosphorylation on tyrosine, threonine and serine residues. Since abnormal phosphorylation is associated with various pathologies, it was of interest to perform a phosphoproteomic profiling of age-related skeletal muscle degeneration. We used the fluorescent phospho-specific Pro-Q Diamond dye to determine whether changes in the overall phosphorylation of the soluble skeletal muscle proteome differs significantly between young adult and senescent fibres. As an established model system of sarcopenia, we employed 30-month-old rat gastrocnemius fibres. Following the mass spectrometric identification of 59 major 2-D phosphoprotein landmark spots, the fluorescent dye staining survey revealed that 22 muscle proteins showed a differential expression pattern between 3-month- and 30-month-old muscle. Increased phosphorylation levels were shown for myosin light chain 2, tropomyosin alpha, lactate dehydrogenase, desmin, actin, albumin and aconitase. In contrast, decreased phospho-specific dye binding was observed for cytochrome c oxidase, creatine kinase and enolase. Thus, aging-induced alterations in phosphoproteins appear to involve the contractile machinery and the cytoskeleton, as well as the cytosolic and mitochondrial metabolism. This confirms that sarcopenia of old age is a complex neuromuscular pathology that is associated with drastic changes in the abundance and structure of key muscle proteins. PMID:18575773

  5. Nasal Septal Deviation and Facial Skeletal Asymmetries.

    Science.gov (United States)

    Hartman, Christopher; Holton, Nathan; Miller, Steven; Yokley, Todd; Marshall, Steven; Srinivasan, Sreedevi; Southard, Thomas

    2016-03-01

    During ontogeny, the nasal septum exerts a morphogenetic influence on the surrounding facial skeleton. While the influence of the septum is well established in long snouted animal models, its role in human facial growth is less clear. If the septum is a facial growth center in humans, we would predict that deviated septal growth would be associated with facial skeletal asymmetries. Using computed tomographic (CT) scans of n = 55 adult subjects, the purpose of this study was to test whether there is a correlation between septal deviation and facial asymmetries using three-dimensional (3D) geometric morphometric techniques. We calculated deviation as a percentage of septal volume relative to the volume of a modeled non-deviated septum. We then recorded skeletal landmarks representing the nasal, palatal, and lateral facial regions. Landmark data were superimposed using Procrustes analysis. First, we examined the correlation between nasal septal deviation and the overall magnitude of asymmetry. Next, we assessed whether there was a relationship between nasal septal deviation and more localized aspects of asymmetry using multivariate regression analysis. Our results indicate that while there was no correlation between septal deviation and the overall magnitude of asymmetry, septal deviation was associated with asymmetry primarily in the nasal floor and the palatal region. Septal deviation was unassociated with asymmetries in the lateral facial skeleton. Though we did not test the causal relationship between nasal septal deviation and facial asymmetry, our results suggest that the nasal septum may have an influence on patterns of adult facial form. PMID:26677010

  6. MR appearance of skeletal neoplasms following cryotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, M.L. [Dept. of Radiology SB-05, Washington Univ., Seattle, WA (United States); Lough, L.R. [Pitts Radiological Associates, Columbia, SC (United States); Shuman, W.P. [Dept. of Radiology, Medical Center Hospital of Vermont, Burlington, VT (United States); Lazerte, G.D. [Dept. of Pathology RC-72, Washington Univ., Medical Center Hospital of Vermont, Burlington, VT (United States); Conrad, E.U. [Dept. of Orthopedic Surgery RK-10, Washington Univ., Medical Center of Vermont, Burlington, VT (United States)

    1994-02-01

    Cryotherapy is an increasingly popular mode of therapy adjunctive to surgical curettage in the treatment of certain skeletal neoplasms, such as giant cell tumors or chondrosarcomas. The magnetic resonance (MR) findings following cryotherapy have not been previously reported. We reviewed the MR findings in seven patients with skeletal neoplasms following curettage and cryotherapy. In six cases we found a zone of varying thickness extending beyond the surgical margins, corresponding to an area of cryoinjury to medullary bone. This zone displayed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, consistent with the presence of marrow edema. This zone of edema almost certainly reflects underlying thermal osteonecrosis. This zone may vary in size and intensity over time as the area of cryoinjury evolves or resolves. MR is currently the imaging procedure of choice for follow-up of most musculoskeletal neoplasms. Knowledge of the MR findings following cryotherapy should help prevent confusion during the interpretation of follow-up MR examinations. (orig.)

  7. MR appearance of skeletal neoplasms following cryotherapy

    International Nuclear Information System (INIS)

    Cryotherapy is an increasingly popular mode of therapy adjunctive to surgical curettage in the treatment of certain skeletal neoplasms, such as giant cell tumors or chondrosarcomas. The magnetic resonance (MR) findings following cryotherapy have not been previously reported. We reviewed the MR findings in seven patients with skeletal neoplasms following curettage and cryotherapy. In six cases we found a zone of varying thickness extending beyond the surgical margins, corresponding to an area of cryoinjury to medullary bone. This zone displayed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, consistent with the presence of marrow edema. This zone of edema almost certainly reflects underlying thermal osteonecrosis. This zone may vary in size and intensity over time as the area of cryoinjury evolves or resolves. MR is currently the imaging procedure of choice for follow-up of most musculoskeletal neoplasms. Knowledge of the MR findings following cryotherapy should help prevent confusion during the interpretation of follow-up MR examinations. (orig.)

  8. Analysis of the distribution of HLA-A alleles in populations from five continents.

    Science.gov (United States)

    Middleton, D; Williams, F; Meenagh, A; Daar, A S; Gorodezky, C; Hammond, M; Nascimento, E; Briceno, I; Perez, M P

    2000-10-01

    The variation and frequency of HLA-A genotypes were established by PCR-SSOP typing in diverse geographically distributed populations: Brazilian, Colombian Kogui, Cuban, Mexican, Omani, Singapore Chinese, and South African Zulu. HLA-A allelic families with only one allele were identified for HLA-A*01, -A*23, -A*25, -A*31, -A*32, -A*36, -A*43, -A*69, -A*80; and with two alleles for HLA-A*03, -A*11, -A*26, -A*29, -A*33, -A*34, and -A*66. Greater variation was detected for HLA-A*02, -A*24, and -A*68 allele families. Colombian Kogui and Mexican Seris showed the least diversity with respect to HLA-A alleles, albeit with small numbers tested, with only four and five HLA-A alleles identified, respectively. It would appear by their presence in all populations studied, either rural or indigenous, that certain alleles are very important in pathogen peptide presentation. PMID:11082518

  9. Allelic Diversity of Major Histocompatibility Complex Class II DRB Gene in Indian Cattle and Buffalo

    Directory of Open Access Journals (Sweden)

    Sachinandan De

    2011-01-01

    Full Text Available The present study was conducted to study the diversity of MHC-DRB3 alleles in Indian cattle and buffalo breeds. Previously reported BoLA-DRB exon 2 alleles of Indian Zebu cattle, Bos taurus cattle, buffalo, sheep, and goats were analyzed for the identities and divergence among various allele sequences. Comparison of predicted amino acid residues of DRB3 exon 2 alleles with similar alleles from other ruminants revealed considerable congruence in amino acid substitution pattern. These alleles showed a high degree of nucleotide and amino acid polymorphism at positions forming peptide-binding regions. A higher rate of nonsynonymous substitution was detected at the peptide-binding regions, indicating that BoLA-DRB3 allelic sequence evolution was driven by positive selection.

  10. Effects of the APOE ε2 Allele on Mortality and Cognitive Function in the Oldest Old

    DEFF Research Database (Denmark)

    Lindahl-Jacobsen, Rune; Tan, Qihua; Mengel-From, Jonas;

    2013-01-01

    . We did not find a protective effect of the APOE ε2 allele on mortality among the oldest old, but in agreement with our previous findings, we found a 22% increased mortality risk for APOE ε4 carriers. The APOE ε2 allele may be protective on cognitive decline among the oldest old.......Some studies indicate that the APOE ε2 allele may have a protective effect on mortality and mental health among the elderly adults. We investigated the effect of the APOE ε2 allele on cognitive function and mortality in 1651 members of the virtually extinct Danish 1905 birth cohort. We found...... no protective effect of the APOE ε2 allele on mortality compared with the APOE ε3 allele. The point estimates indicated an increased protection against cognitive decline over time for persons with the APOE ε2 allele. Cognitive score did not significantly modify the mortality risk of the various APOE genotypes...

  11. FOXO1 delays skeletal muscle regeneration and suppresses myoblast proliferation.

    Science.gov (United States)

    Yamashita, Atsushi; Hatazawa, Yukino; Hirose, Yuma; Ono, Yusuke; Kamei, Yasutomi

    2016-08-01

    Unloading stress, such as bed rest, inhibits the regenerative potential of skeletal muscles; however, the underlying mechanisms remain largely unknown. FOXO1 expression, which induces the upregulated expression of the cell cycle inhibitors p57 and Gadd45α, is known to be increased in the skeletal muscle under unloading conditions. However, there is no report addressing FOXO1-induced inhibition of myoblast proliferation. Therefore, we induced muscle injury by cardiotoxin in transgenic mice overexpressing FOXO1 in the skeletal muscle (FOXO1-Tg mice) and observed regeneration delay in skeletal muscle mass and cross-sectional area in FOXO1-Tg mice. Increased p57 and Gadd45α mRNA levels, and decreased proliferation capacity were observed in C2C12 myoblasts expressing a tamoxifen-inducible active form of FOXO1. These results suggest that decreased proliferation capacity of myoblasts by FOXO1 disrupts skeletal muscle regeneration under FOXO1-increased conditions, such as unloading. PMID:27010781

  12. Dynamics of the skeletal muscle secretome during myoblast differentiation

    DEFF Research Database (Denmark)

    Henningsen, Jeanette; Rigbolt, Kristoffer T G; Blagoev, Blagoy;

    2010-01-01

    During recent years, increased efforts have focused on elucidating the secretory function of skeletal muscle. Through secreted molecules, skeletal muscle affects local muscle biology in an auto/paracrine manner as well as having systemic effects on other tissues. Here we used a quantitative...... proteomics platform to investigate the factors secreted during the differentiation of murine C2C12 skeletal muscle cells. Using triple encoding stable isotope labeling by amino acids in cell culture, we compared the secretomes at three different time points of muscle differentiation and followed the dynamics...... of the skeletal muscle as a prominent secretory organ. In addition to previously reported molecules, we identified many secreted proteins that have not previously been shown to be released from skeletal muscle cells nor shown to be differentially released during the process of myogenesis. We found 188...

  13. Low frequency of the scrapile resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed

    NARCIS (Netherlands)

    Acutis, P.L.; Sbaiz, L.; Verburg, F.J.; Riina, M.V.; Ru, G.; Moda, G.; Caramelli, M.; Bossers, A.

    2004-01-01

    Frequencies of polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene were studied in 1207 pure-bred and cross-bred Italian Biellese rams, a small ovine breed of about 65 000 head in Italy. Aside from the five most common alleles (VRQ, ARQ, ARR, AHQ and ARH), the rare ARK allele wa

  14. Microsatellite allele A5.1 of MHC class I chain-related gene A is associated with latent autoimmune diabetes in adults in Latvia.

    Science.gov (United States)

    Berzina, L; Shtauvere-Brameus, A; Rumba, I; Sanjeevi, C B

    2002-04-01

    NIDDM is one of the most common forms of diabetes. The diagnosis is based on WHO classification, which is a clinical classification and misses the autoimmune diabetes in adults. Therefore, among the clinically diagnosed NIDDM cases, there can be a certain number of patients with latent autoimmune diabetes in adults (LADA). The MICA gene is located in the MHC class I region and is expressed by monocytes, keratinocytes, and endothelial cells. Sequence determination of the MICA gene identifies trinucleotide repeat (GCT) microsatellite polymorphism, which identifies 5 alleles with 4, 5, 6, and 9 repetitions of GCT (A4, A5, A6, and A9) or 5 repetitions of GCT with 1 additional G insertion for allele A5.1. From our previous studies, we have shown that microsatellite allele A5 of MICA is associated with IDDM. The aim of this study was to test the hypothesis that certain MICA alleles are associated with LADA among clinically diagnosed NIDDM. Out of 100 clinically diagnosed NIDDM patients, 49 tested positive for GAD65 and IA-2 antibodies by use of 35S RIA. Samples from these 49 patients and 96 healthy controls were analyzed for MICA by PCR amplification, and fragment sizes were determined in an ABI prism DNA sequencer. Our results show that MICA allele A5.1 is significantly increased in antibody-positive (GAD65 or IA-2) NIDDM patients [35/49 (72%)] when compared to healthy controls [22/96 (23%)] (OR = 8.4; P < 0.0001). However, we do not see any association with each of the antibodies separately. From our study, we conclude that (a) MICA allele A5.1 is associated with LADA and (b) MICA may play an important role in the etiopathogenesis of LADA.

  15. Magnetic Separation in Romania

    OpenAIRE

    Rezlescu, Nicolae; Bradu, Elena-Brandusa; Iacob, Gheorghe; Badescu, Vasile; Iacob, Lavinia

    1986-01-01

    The utilization of the magnetic separators of foreign and Romanian source is presented and the most important achievements in research, engineering design and manufacturing activity concerning the magnetic separation in Romania are reviewed.

  16. Magnetic Separation in Czechoslovakia

    OpenAIRE

    Hencl, Vladimir

    1991-01-01

    The use of magnetic separation in various mineral processing facilities in Czechoslovakia is described. The manufacture of assorted types of magnetic separation machines is highlighted. Potential applications and research and development activities are discussed.

  17. Magnetic separation of algae

    Energy Technology Data Exchange (ETDEWEB)

    Nath, Pulak; Twary, Scott N.

    2016-04-26

    Described herein are methods and systems for harvesting, collecting, separating and/or dewatering algae using iron based salts combined with a magnetic field gradient to separate algae from an aqueous solution.

  18. Skeletal stem cell isolation: A review on the state-of-the-art microfluidic label-free sorting techniques.

    Science.gov (United States)

    Xavier, Miguel; Oreffo, Richard O C; Morgan, Hywel

    2016-01-01

    Skeletal stem cells (SSC) are a sub-population of bone marrow stromal cells that reside in postnatal bone marrow with osteogenic, chondrogenic and adipogenic differentiation potential. SSCs reside only in the bone marrow and have organisational and regulatory functions in the bone marrow microenvironment and give rise to the haematopoiesis-supportive stroma. Their differentiation capacity is restricted to skeletal lineages and therefore the term SSC should be clearly distinguished from mesenchymal stem cells which are reported to exist in extra-skeletal tissues and, critically, do not contribute to skeletal development. SSCs are responsible for the unique regeneration capacity of bone and offer unlimited potential for application in bone regenerative therapies. A current unmet challenge is the isolation of homogeneous populations of SSCs, in vitro, with homogeneous regeneration and differentiation capacities. Challenges that limit SSC isolation include a) the scarcity of SSCs in bone marrow aspirates, estimated at between 1 in 10-100,000 mononuclear cells; b) the absence of specific markers and thus the phenotypic ambiguity of the SSC and c) the complexity of bone marrow tissue. Microfluidics provides innovative approaches for cell separation based on bio-physical features of single cells. Here we review the physical principles underlying label-free microfluidic sorting techniques and review their capacity for stem cell selection/sorting from complex (heterogeneous) samples. PMID:27236022

  19. Allele mining and enhanced genetic recombination for rice breeding.

    Science.gov (United States)

    Leung, Hei; Raghavan, Chitra; Zhou, Bo; Oliva, Ricardo; Choi, Il Ryong; Lacorte, Vanica; Jubay, Mona Liza; Cruz, Casiana Vera; Gregorio, Glenn; Singh, Rakesh Kumar; Ulat, Victor Jun; Borja, Frances Nikki; Mauleon, Ramil; Alexandrov, Nickolai N; McNally, Kenneth L; Sackville Hamilton, Ruaraidh

    2015-12-01

    Traditional rice varieties harbour a large store of genetic diversity with potential to accelerate rice improvement. For a long time, this diversity maintained in the International Rice Genebank has not been fully used because of a lack of genome information. The publication of the first reference genome of Nipponbare by the International Rice Genome Sequencing Project (IRGSP) marked the beginning of a systematic exploration and use of rice diversity for genetic research and breeding. Since then, the Nipponbare genome has served as the reference for the assembly of many additional genomes. The recently completed 3000 Rice Genomes Project together with the public database (SNP-Seek) provides a new genomic and data resource that enables the identification of useful accessions for breeding. Using disease resistance traits as case studies, we demonstrated the power of allele mining in the 3,000 genomes for extracting accessions from the GeneBank for targeted phenotyping. Although potentially useful landraces can now be identified, their use in breeding is often hindered by unfavourable linkages. Efficient breeding designs are much needed to transfer the useful diversity to breeding. Multi-parent Advanced Generation InterCross (MAGIC) is a breeding design to produce highly recombined populations. The MAGIC approach can be used to generate pre-breeding populations with increased genotypic diversity and reduced linkage drag. Allele mining combined with a multi-parent breeding design can help convert useful diversity into breeding-ready genetic resources. PMID:26606925

  20. Allele frequency of CODIS 13 in Indonesian population.

    Science.gov (United States)

    Untoro, Evi; Atmadja, Djaja Surya; Pu, Chang-En; Wu, Fang-Chi

    2009-04-01

    Since the first application of DNA technology in 1985 in forensic cases, and the acceptance of this technology in 1988 at court, the DNA typing is widely used in personal identification, parentage cases and tracing the source of biological samples found in the crime scene. The FBI on 1990 had recommended the forensic labs to used 13 loci of Short Tandem Repeats (STR), known as CODIS 13, as the loci of choice for forensic use. The research on the population DNA database on these loci is extremely important for calculating the Paternity Index as well as Matching Probability for forensic application of DNA technology. As many as 402 unrelated persons, consisted of 322 from western part of Indonesia and 80 from eastern part of Indonesia, were chosen as the respondents of this research, after signing the informed consent. The peripheral blood sample was taken using sterile lancets and dropped onto FTA classic cards. The DNA was extracted by FTA purification solution (3x) and TE(-1) (2x), and amplified by PCR mix, either Cofiler or Profiler Plus (Perkin Elmers), followed by sequencing using ABI Prism type 3100 Avant Genetic Analyzer. The analysis showed that the alleles frequencies of Indonesian is specific, different with the other Asian populations with some specific alleles and microvariant were found. PMID:19261522

  1. Allele frequency of CODIS 13 in Indonesian population.

    Science.gov (United States)

    Untoro, Evi; Atmadja, Djaja Surya; Pu, Chang-En; Wu, Fang-Chi

    2009-04-01

    Since the first application of DNA technology in 1985 in forensic cases, and the acceptance of this technology in 1988 at court, the DNA typing is widely used in personal identification, parentage cases and tracing the source of biological samples found in the crime scene. The FBI on 1990 had recommended the forensic labs to used 13 loci of Short Tandem Repeats (STR), known as CODIS 13, as the loci of choice for forensic use. The research on the population DNA database on these loci is extremely important for calculating the Paternity Index as well as Matching Probability for forensic application of DNA technology. As many as 402 unrelated persons, consisted of 322 from western part of Indonesia and 80 from eastern part of Indonesia, were chosen as the respondents of this research, after signing the informed consent. The peripheral blood sample was taken using sterile lancets and dropped onto FTA classic cards. The DNA was extracted by FTA purification solution (3x) and TE(-1) (2x), and amplified by PCR mix, either Cofiler or Profiler Plus (Perkin Elmers), followed by sequencing using ABI Prism type 3100 Avant Genetic Analyzer. The analysis showed that the alleles frequencies of Indonesian is specific, different with the other Asian populations with some specific alleles and microvariant were found.

  2. Allelic variations of glut-1 deficiency syndrome: the chinese experience.

    Science.gov (United States)

    Liu, Yanyan; Bao, Xinhua; Wang, Dong; Fu, Na; Zhang, Xiaoying; Cao, Guangna; Song, Fuying; Wang, Shuang; Zhang, Yuehua; Qin, Jiong; Yang, Hong; Engelstad, Kristin; De Vivo, Darryl C; Wu, Xiru

    2012-07-01

    Glucose transporter type 1 deficiency syndrome is characterized by infantile onset seizures, development delay, movement disorders, and acquired microcephaly. The phenotype includes allelic variants such as intermittent ataxia, choreoathetosis, dystonia, and alternating hemiplegia of childhood with or without epilepsy. Dystonias involve allelic variants of glucose transporter type 1 deficiency syndrome. Three Chinese patients presented with paroxysmal behavioral disturbance, weakness, ataxia (especially after fasting), and exercise intolerance. Electroencephalogram findings did not correlate with clinical manifestations. Cranial magnetic resonance imaging produced normal results or mild hypomyelination. Hypoglycorrhachia was evident in all cases. Cerebrospinal fluid glucose ranged from 1.63-2.45 mmol/L. Erythrocyte 3-O-methyl-d-glucose uptake was decreased to 58% in patient 1. Three SLC2A1 disease-causing mutations (761delA, P383H, and R400C) were observed. No patient tolerated ketogenic diets. Two patients responded to frequent meals with snacks. Cerebrospinal fluid evaluation constitutes the diagnostic testing permitting early treatment of glucose transporter type 1 deficiency syndrome. Early diagnosis and treatment improve prognoses. PMID:22704013

  3. An allele of the crm gene blocks cyanobacterial circadian rhythms.

    Science.gov (United States)

    Boyd, Joseph S; Bordowitz, Juliana R; Bree, Anna C; Golden, Susan S

    2013-08-20

    The SasA-RpaA two-component system constitutes a key output pathway of the cyanobacterial Kai circadian oscillator. To date, rhythm of phycobilisome associated (rpaA) is the only gene other than kaiA, kaiB, and kaiC, which encode the oscillator itself, whose mutation causes completely arrhythmic gene expression. Here we report a unique transposon insertion allele in a small ORF located immediately upstream of rpaA in Synechococcus elongatus PCC 7942 termed crm (for circadian rhythmicity modulator), which results in arrhythmic promoter activity but does not affect steady-state levels of RpaA. The crm ORF complements the defect when expressed in trans, but only if it can be translated, suggesting that crm encodes a small protein. The crm1 insertion allele phenotypes are distinct from those of an rpaA null; crm1 mutants are able to grow in a light:dark cycle and have no detectable oscillations of KaiC phosphorylation, whereas low-amplitude KaiC phosphorylation rhythms persist in the absence of RpaA. Levels of phosphorylated RpaA in vivo measured over time are significantly altered compared with WT in the crm1 mutant as well as in the absence of KaiC. Taken together, these results are consistent with the hypothesis that the Crm polypeptide modulates a circadian-specific activity of RpaA.

  4. Cardiac-Restricted Expression of VCP/TER94 RNAi or Disease Alleles Perturbs Drosophila Heart Structure and Impairs Function

    Science.gov (United States)

    Viswanathan, Meera C.; Blice-Baum, Anna C.; Sang, Tzu-Kang; Cammarato, Anthony

    2016-01-01

    Valosin-containing protein (VCP) is a highly conserved mechanoenzyme that helps maintain protein homeostasis in all cells and serves specialized functions in distinct cell types. In skeletal muscle, it is critical for myofibrillogenesis and atrophy. However, little is known about VCP's role(s) in the heart. Its functional diversity is determined by differential binding of distinct cofactors/adapters, which is likely disrupted during disease. VCP mutations cause multisystem proteinopathy (MSP), a pleiotropic degenerative disorder that involves inclusion body myopathy. MSP patients display progressive muscle weakness. They also exhibit cardiomyopathy and die from cardiac and respiratory failure, which are consistent with critical myocardial roles for the enzyme. Nonetheless, efficient models to interrogate VCP in cardiac muscle remain underdeveloped and poorly studied. Here, we investigated the significance of VCP and mutant VCP in the Drosophila heart. Cardiac-restricted RNAi-mediated knockdown of TER94, the Drosophila VCP homolog, severely perturbed myofibrillar organization and heart function in adult flies. Furthermore, expression of MSP disease-causing alleles engendered cardiomyopathy in adults and structural defects in embryonic hearts. Drosophila may therefore serve as a valuable model for examining role(s) of VCP in cardiogenesis and for identifying novel heart-specific VCP interactions, which when disrupted via mutation, contribute to or elicit cardiac pathology. PMID:27500162

  5. Endochondral ossification pathway genes and postmenopausal osteoporosis: Association and specific allele related serum bone sialoprotein levels in Han Chinese.

    Science.gov (United States)

    Zhang, Yunzhi; Liu, Haiyan; Zhang, Chen; Zhang, Tianxiao; Zhang, Bo; Li, Lu; Chen, Gang; Fu, Dongke; Wang, KunZheng

    2015-11-16

    Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and disrupted bone architecture, predisposing the patient to increased fracture risk. Evidence from early genetic epidemiological studies has indicated a major role for genetics in the development of osteoporosis and the variation in BMD. In this study, we focused on two key genes in the endochondral ossification pathway, IBSP and PTHLH. Over 9,000 postmenopausal Han Chinese women were recruited, and 54 SNPs were genotyped. Two significant SNPs within IBSP, rs1054627 and rs17013181, were associated with BMD and postmenopausal osteoporosis by the two-stage strategy, and rs17013181 was also significantly associated with serum IBSP levels. Moreover, one haplotype (rs12425376-rs10843047-rs42294) covering the 5' end of PTHLH was associated with postmenopausal osteoporosis. Our results provide evidence for the association of these two key endochondral ossification pathway genes with BMD and osteoporosis in postmenopausal Han Chinese women. Combined with previous findings, we provide evidence that a particular SNP in IBSP has an allele-specific effect on mRNA levels, which would, in turn, reflect serum IBSP levels.

  6. Oxidative stress and mitochondrial impairment can be separated from lipofuscin accumulation in aged human skeletal muscle

    DEFF Research Database (Denmark)

    Hütter, Eveline; Skovbro, Mette; Lener, Barbara;

    2007-01-01

    According to the free radical theory of aging, reactive oxygen species (ROS) act as a driving force of the aging process, and it is generally believed that mitochondrial dysfunction is a major source of increased oxidative stress in tissues with high content of mitochondria, such as muscle or brain...

  7. Raman spectroscopy and coherent anti-Stokes Raman scattering imaging: prospective tools for monitoring skeletal cells and skeletal regeneration

    Science.gov (United States)

    Moura, Catarina Costa; Tare, Rahul S.; Oreffo, Richard O. C.; Mahajan, Sumeet

    2016-01-01

    The use of skeletal stem cells (SSCs) for cell-based therapies is currently one of the most promising areas for skeletal disease treatment and skeletal tissue repair. The ability for controlled modification of SSCs could provide significant therapeutic potential in regenerative medicine, with the prospect to permanently repopulate a host with stem cells and their progeny. Currently, SSC differentiation into the stromal lineages of bone, fat and cartilage is assessed using different approaches that typically require cell fixation or lysis, which are invasive or even destructive. Raman spectroscopy and coherent anti-Stokes Raman scattering (CARS) microscopy present an exciting alternative for studying biological systems in their natural state, without any perturbation. Here we review the applications of Raman spectroscopy and CARS imaging in stem-cell research, and discuss the potential of these two techniques for evaluating SSCs, skeletal tissues and skeletal regeneration as an exemplar. PMID:27170652

  8. NF-κB inhibition reveals a novel role for HGF during skeletal muscle repair.

    Science.gov (United States)

    Proto, J D; Tang, Y; Lu, A; Chen, W C W; Stahl, E; Poddar, M; Beckman, S A; Robbins, P D; Nidernhofer, L J; Imbrogno, K; Hannigan, T; Mars, W M; Wang, B; Huard, J

    2015-01-01

    The transcription factor nuclear factor κB (NF-κB)/p65 is the master regulator of inflammation in Duchenne muscular dystrophy (DMD). Disease severity is reduced by NF-κB inhibition in the mdx mouse, a murine DMD model; however, therapeutic targeting of NF-κB remains problematic for patients because of its fundamental role in immunity. In this investigation, we found that the therapeutic effect of NF-κB blockade requires hepatocyte growth factor (HGF) production by myogenic cells. We found that deleting one allele of the NF-κB subunit p65 (p65+/-) improved the survival and enhanced the anti-inflammatory capacity of muscle-derived stem cells (MDSCs) following intramuscular transplantation. Factors secreted from p65+/- MDSCs in cell cultures modulated macrophage cytokine expression in an HGF-receptor-dependent manner. Indeed, we found that following genetic or pharmacologic inhibition of basal NF-κB/p65 activity, HGF gene transcription was induced in MDSCs. We investigated the role of HGF in anti-NF-κB therapy in vivo using mdx;p65+/- mice, and found that accelerated regeneration coincided with HGF upregulation in the skeletal muscle. This anti-NF-κB-mediated dystrophic phenotype was reversed by blocking de novo HGF production by myogenic cells following disease onset. HGF silencing resulted in increased inflammation and extensive necrosis of the diaphragm muscle. Proteolytic processing of matrix-associated HGF is known to activate muscle stem cells at the earliest stages of repair, but our results indicate that the production of a second pool of HGF by myogenic cells, negatively regulated by NF-κB/p65, is crucial for inflammation resolution and the completion of repair in dystrophic skeletal muscle. Our findings warrant further investigation into the potential of HGF mimetics for the treatment of DMD. PMID:25906153

  9. Rapid chemical separations

    CERN Document Server

    Trautmann, N

    1976-01-01

    A survey is given on the progress of fast chemical separation procedures during the last few years. Fast, discontinuous separation techniques are illustrated by a procedure for niobium. The use of such techniques for the chemical characterization of the heaviest known elements is described. Other rapid separation methods from aqueous solutions are summarized. The application of the high speed liquid chromatography to the separation of chemically similar elements is outlined. The use of the gas jet recoil transport method for nuclear reaction products and its combination with a continuous solvent extraction technique and with a thermochromatographic separation is presented. Different separation methods in the gas phase are briefly discussed and the attachment of a thermochromatographic technique to an on-line mass separator is shown. (45 refs).

  10. Overexpression of SMPX in adult skeletal muscle does not change skeletal muscle fiber type or size.

    Directory of Open Access Journals (Sweden)

    Einar Eftestøl

    Full Text Available Mechanical factors such as stretch are thought to be important in the regulation of muscle phenotype. Small muscle protein X-linked (SMPX is upregulated by stretch in skeletal muscle and has been suggested to serve both as a transcription factor and a mechanosensor, possibly giving rise to changes in both fiber size and fiber type. We have used in vivo confocal imaging to study the subcellular localization of SMPX in skeletal muscle fibers of adult rats using a SMPX-EGFP fusion protein. The fusion protein was localized predominantly in repetitive double stripes flanking the Z-disc, and was excluded from all nuclei. This localization would be consistent with SMPX being a mechanoreceptor, but not with SMPX playing a role as a transcription factor. In vivo overexpression of ectopic SMPX in skeletal muscle of adult mice gave no significant changes in fiber type distribution or cross sectional area, thus a role of SMPX in regulating muscle phenotype remains unclear.

  11. Myofibre damage in human skeletal muscle

    DEFF Research Database (Denmark)

    Crameri, R M; Aagaard, P; Qvortrup, K;

    2007-01-01

    humans using voluntary exercise. Untrained males (n=8, range 22-27 years) performed 210 maximal eccentric contractions with each leg on an isokinetic dynamometer, voluntarily (VOL) with one leg and electrically induced (ES) with the other leg. Assessments from the skeletal muscle were obtained prior to......Disruption to proteins within the myofibre after a single bout of unaccustomed eccentric exercise is hypothesized to induce delayed onset of muscle soreness and to be associated with an activation of satellite cells. This has been shown in animal models using electrical stimulation but not in...... exercise and at 5, 24, 96 and 192 h postexercise. Muscle tenderness rose in VOL and ES after 24 h, and did not differ between groups. Maximal isometric contraction strength, rate of force development and impulse declined in the VOL leg from 4 h after exercise, but not in ES (except at 24 h). In contrast, a...

  12. Malignant fibrous histiocytoma with skeletal involvement

    Directory of Open Access Journals (Sweden)

    Takechi,Hideo

    1978-10-01

    Full Text Available Malignant fibrous histiocytoma of soft part is rather common but malignant fibrous histiocytoma of the bone is rarely encountered clinically. Authors present five cases of malignant fibrous histiocytoma with skeletal involvement and discuss their clinical course, x-ray findings and histological features. This tumor has marked tendency for local recurrence and metastasis. Other bone tumors such as giant cell tumor, aneurysmal bone cyst, non ossifying fibroma, osteosarcoma, fibrosarcoma of bone and metastatic cancer can be excluded by several characteristic findings observed in x-rays as well as histopathological features. All information on the patient should be carefully analysed, because it is difficult to decide whether bone involvement is primary or secondary. Four out of five cases definitely originated within the bone.

  13. Tissue Engineered Strategies for Skeletal Muscle Injury

    Directory of Open Access Journals (Sweden)

    Umile Giuseppe Longo

    2012-01-01

    Full Text Available Skeletal muscle injuries are common in athletes, occurring with direct and indirect mechanisms and marked residual effects, such as severe long-term pain and physical disability. Current therapy consists of conservative management including RICE protocol (rest, ice, compression, and elevation, nonsteroidal anti-inflammatory drugs, and intramuscular corticosteroids. However, current management of muscle injuries often does not provide optimal restoration to preinjury status. New biological therapies, such as injection of platelet-rich plasma and stem-cell-based therapy, are appealing. Although some studies support PRP application in muscle-injury management, reasons for concern persist, and further research is required for a standardized and safe use of PRP in clinical practice. The role of stem cells needs to be confirmed, as studies are still limited and inconsistent. Further research is needed to identify mechanisms involved in muscle regeneration and in survival, proliferation, and differentiation of stem cells.

  14. Mining skeletal phenotype descriptions from scientific literature.

    Directory of Open Access Journals (Sweden)

    Tudor Groza

    Full Text Available Phenotype descriptions are important for our understanding of genetics, as they enable the computation and analysis of a varied range of issues related to the genetic and developmental bases of correlated characters. The literature contains a wealth of such phenotype descriptions, usually reported as free-text entries, similar to typical clinical summaries. In this paper, we focus on creating and making available an annotated corpus of skeletal phenotype descriptions. In addition, we present and evaluate a hybrid Machine Learning approach for mining phenotype descriptions from free text. Our hybrid approach uses an ensemble of four classifiers and experiments with several aggregation techniques. The best scoring technique achieves an F-1 score of 71.52%, which is close to the state-of-the-art in other domains, where training data exists in abundance. Finally, we discuss the influence of the features chosen for the model on the overall performance of the method.

  15. Anisotropic photon migration in human skeletal muscle

    International Nuclear Information System (INIS)

    It is demonstrated in the short head of the human biceps brachii of 16 healthy subjects (12 males and 4 females) that near infrared photon migration is anisotropic. The probability for a photon to travel along the direction of the muscle fibres is higher (∼0.4) than that of travelling along a perpendicular axis (∼0.3) while in the adipose tissue the probability is the same (∼0.33) in all directions. Considering that the muscle fibre orientation is different depending on the type of muscle considered, and that inside a given skeletal muscle the orientation may change, the present findings in part might explain the intrasubject variability observed in the physiological parameters measured by near infrared spectroscopy techniques. In other words, the observed regional differences might not only be physiological differences but also optical artefacts. (note)

  16. Karate moves recognition from skeletal motion

    Science.gov (United States)

    Bianco, Simone; Tisato, Francesco

    2013-03-01

    This work aims at automatically recognizing sequences of complex karate movements and giving a measure of the quality of the movements performed. Since this is a problem which intrinsically needs a 3D model, in this work we propose a solution taking as input sequences of skeletal motions that can derive from both motion capture hardware or consumer-level, off the shelf, depth sensing systems. The proposed system is constituted by four different modules: skeleton representation, pose classification, temporal alignment, and scoring. The proposed system is tested on a set of different punch, kick and defense karate moves executed starting from the simplest case, i.e. fixed static stances (heiko dachi) up to sequences in which the starting stances is different from the ending one. The dataset has been recorded using a single Microsoft Kinect. The dataset includes the recordings of both male and female athletes with different skill levels, ranging from novices to masters.

  17. Emerging targeted drug therapies in skeletal dysplasias.

    Science.gov (United States)

    Yap, Patrick; Savarirayan, Ravi

    2016-10-01

    Quantum advances have occurred in the field of human genetics in the six decades since Watson and Crick expressed their "wish to suggest a structure for the salt of deoxyribose nucleic acid." These culminated with the human genome project, which has opened up myriad possibilities, including that of individualized genetic medicine, the ability to deliver medical advice, management, and therapy tailored to an individual's genetic blueprint. Advances in genetic diagnostic capabilities have been rapid, to the point where the genome can be sequenced for several thousand dollars. Crucially, it has facilitated the identification of targets for "precision" treatments to combat genetic diseases at their source. This manuscript will review the innovative, pathogenesis-based therapies that are revolutionizing management of skeletal dysplasias, giving patients and families new options and outcomes. © 2016 Wiley Periodicals, Inc. PMID:27155200

  18. Monitoring of progressive collapse of skeletal structures

    International Nuclear Information System (INIS)

    The authors propose an idea of monitoring the state of skeletal structures of high importance (e.g. roof structures over large area buildings) with the aim of identification of slowly-developing plastic zones. This is formulated as an inverse problem within the framework of the Virtual Distortion Method, which was used previously to identify stiffness/mass modifications in similar manner. Permanent plastic strains developed in a truss element can be modeled by an initial strain (virtual distortion) introduced to the structure. The formation of subsequent plastic zones in the structure is assumed to be slow. Consequently, the design variable (plastic strain) is time-independent, which makes the inverse analysis efficient. This article presents problem formulation and numerical algorithm for identification of the plastic strains int russ structures. The identification relies on gradient-based optimization. A numerical example is included to demonstrate the efficiency of the algorithm.

  19. Dysphagia due to Diffuse Idiopathic Skeletal Hyperostosis

    Directory of Open Access Journals (Sweden)

    Masafumi Ohki

    2012-01-01

    Full Text Available Diffuse idiopathic skeletal hyperostosis (DISH is usually asymptomatic. However, rarely, it causes dysphagia, hoarseness, dyspnea, snoring, stridor, and laryngeal edema. Herein, we present a patient with DISH causing dysphagia. A 70-year-old man presented with a 4-month history of sore throat, dysphagia, and foreign body sensation. Flexible laryngoscopy revealed a leftward-protruding posterior wall in the hypopharynx. Computed tomography and magnetic resonance imaging revealed a bony mass pushing, anteriorly, on the posterior hypopharyngeal wall. Ossification included an osseous bridge involving 5 contiguous vertebral bodies. Dysphagia due to DISH was diagnosed. His symptoms were relieved by conservative therapy using anti-inflammatory drugs. However, if conservative therapy fails and symptoms are severe, surgical treatments must be considered.

  20. Omega-3 Fatty Acids and Skeletal Muscle Health.

    Science.gov (United States)

    Jeromson, Stewart; Gallagher, Iain J; Galloway, Stuart D R; Hamilton, D Lee

    2015-11-19

    Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle.

  1. Muscle-specific microRNAs in skeletal muscle development.

    Science.gov (United States)

    Horak, Martin; Novak, Jan; Bienertova-Vasku, Julie

    2016-02-01

    Proper muscle function constitutes a precondition for good heath and an active lifestyle during an individual's lifespan and any deviations from normal skeletal muscle development and its functions may lead to numerous health conditions including e.g. myopathies and increased mortality. It is thus not surprising that there is an increasing need for understanding skeletal muscle developmental processes and the associated molecular pathways, especially as such information could find further uses in therapy. The understanding of complex skeletal muscle developmental networks was broadened with the discovery of microRNA (miRNA) molecules. MicroRNAs are evolutionary conserved small non-coding RNAs capable of negatively regulating gene expression on a post-transcriptional level by means of miRNA-mRNA interaction. Several miRNAs expressed exclusively in muscle have been labeled myomiRs. MyomiRs represent an integral part of skeletal muscle development, i.e. playing a significant role during skeletal muscle proliferation, differentiation and regeneration. The purpose of this review is to provide a summary of current knowledge regarding the involvement of myomiRs in the individual phases of myogenesis and other aspects of skeletal muscle biology, along with an up-to-date list of myomiR target genes and their functions in skeletal muscle and miRNA-related therapeutic approaches and future prospects. PMID:26708096

  2. Omega-3 Fatty Acids and Skeletal Muscle Health

    Directory of Open Access Journals (Sweden)

    Stewart Jeromson

    2015-11-01

    Full Text Available Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle.

  3. A metabolic link to skeletal muscle wasting and regeneration

    Directory of Open Access Journals (Sweden)

    René eKoopman

    2014-02-01

    Full Text Available Due to its essential role in movement, insulating the internal organs, generating heat to maintain core body temperature, and acting as a major energy storage depot, any impairment to skeletal muscle structure and function may lead to an increase in both morbidity and mortality. In the context of skeletal muscle, altered metabolism is directly associated with numerous pathologies and disorders, including diabetes, and obesity, while many skeletal muscle pathologies have secondary changes in metabolism, including cancer cachexia, sarcopenia and the muscular dystrophies. Furthermore, the importance of cellular metabolism in the regulation of skeletal muscle stem cells is beginning to receive significant attention. Thus, it is clear that skeletal muscle metabolism is intricately linked to the regulation of skeletal muscle mass and regeneration. The aim of this review is to discuss some of the recent findings linking a change in metabolism to changes in skeletal muscle mass, as well as describing some of the recent studies in developmental, cancer and stem-cell biology that have identified a role for cellular metabolism in the regulation of stem cell function, a process termed ‘metabolic reprogramming’.

  4. Compartmentalized ATP synthesis in skeletal muscle triads.

    Science.gov (United States)

    Han, J W; Thieleczek, R; Varsányi, M; Heilmeyer, L M

    1992-01-21

    Isolated skeletal muscle triads contain a compartmentalized glycolytic reaction sequence catalyzed by aldolase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate kinase. These enzymes express activity in the structure-associated state leading to synthesis of ATP in the triadic junction upon supply of glyceraldehyde 3-phosphate or fructose 1,6-bisphosphate. ATP formation occurs transiently and appears to be kinetically compartmentalized, i.e., the synthesized ATP is not in equilibrium with the bulk ATP. The apparent rate constants of the aldolase and the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase reaction are significantly increased when fructose 1,6-bisphosphate instead of glyceraldehyde 3-phosphate is employed as substrate. The observations suggest that fructose 1,6-bisphosphate is especially effectively channelled into the junctional gap. The amplitude of the ATP transient is decreasing with increasing free [Ca2+] in the range of 1 nM to 30 microM. In the presence of fluoride, the ATP transient is significantly enhanced and its declining phase is substantially retarded. This observation suggests utilization of endogenously synthesized ATP in part by structure associated protein kinases and phosphatases which is confirmed by the detection of phosphorylated triadic proteins after gel electrophoresis and autoradiography. Endogenous protein kinases phosphorylate proteins of apparent Mr 450,000, 180,000, 160,000, 145,000, 135,000, 90,000, 54,000, 51,000, and 20,000, respectively. Some of these phosphorylated polypeptides are in the Mr range of known phosphoproteins involved in excitation-contraction coupling of skeletal muscle, which might give a first hint at the functional importance of the sequential glycolytic reactions compartmentalized in triads. PMID:1731894

  5. Real-time PCR genotyping assay for canine progressive rod-cone degeneration and mutant allele frequency in Toy Poodles, Chihuahuas and Miniature Dachshunds in Japan.

    Science.gov (United States)

    Kohyama, Moeko; Tada, Naomi; Mitsui, Hiroko; Tomioka, Hitomi; Tsutsui, Toshihiko; Yabuki, Akira; Rahman, Mohammad Mahbubur; Kushida, Kazuya; Mizukami, Keijiro; Yamato, Osamu

    2016-04-01

    Canine progressive rod-cone degeneration (PRCD) is a middle- to late-onset, autosomal recessive, inherited retinal disorder caused by a substitution (c.5G>A) in the canine PRCD gene that has been identified in 29 or more purebred dogs. In the present study, a TaqMan probe-based real-time PCR assay was developed and evaluated for rapid genotyping and large-scale screening of the mutation. Furthermore, a genotyping survey was carried out in a population of the three most popular breeds in Japan (Toy Poodles, Chihuahuas and Miniature Dachshunds) to determine the current mutant allele frequency. The assay separated all the genotypes of canine PRCD rapidly, indicating its suitability for large-scale surveys. The results of the survey showed that the mutant allele frequency in Toy Poodles was high enough (approximately 0.09) to allow the establishment of measures for the prevention and control of this disorder in breeding kennels. The mutant allele was detected in Chihuahuas for the first time, but the frequency was lower (approximately 0.02) than that in Toy Poodles. The mutant allele was not detected in Miniature Dachshunds. This assay will allow the selective breeding of dogs from the two most popular breeds (Toy Poodle and Chihuahua) in Japan and effective prevention or control of the disorder. PMID:26549343

  6. The miR9863 family regulates distinct Mla alleles in barley to attenuate NLR receptor-triggered disease resistance and cell-death signaling.

    Directory of Open Access Journals (Sweden)

    Jie Liu

    2014-12-01

    Full Text Available Barley (Hordeum vulgare L. Mla alleles encode coiled-coil (CC, nucleotide binding, leucine-rich repeat (NB-LRR receptors that trigger isolate-specific immune responses against the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh. How Mla or NB-LRR genes in grass species are regulated at post-transcriptional level is not clear. The microRNA family, miR9863, comprises four members that differentially regulate distinct Mla alleles in barley. We show that miR9863 members guide the cleavage of Mla1 transcripts in barley, and block or reduce the accumulation of MLA1 protein in the heterologous Nicotiana benthamiana expression system. Regulation specificity is determined by variation in a unique single-nucleotide-polymorphism (SNP in mature miR9863 family members and two SNPs in the Mla miR9863-binding site that separates these alleles into three groups. Further, we demonstrate that 22-nt miR9863s trigger the biogenesis of 21-nt phased siRNAs (phasiRNAs and together these sRNAs form a feed-forward regulation network for repressing the expression of group I Mla alleles. Overexpression of miR9863 members specifically attenuates MLA1, but not MLA10-triggered disease resistance and cell-death signaling. We propose a key role of the miR9863 family in dampening immune response signaling triggered by a group of MLA immune receptors in barley.

  7. Substrate specificity of allelic variants of the TAP peptide transporter.

    Science.gov (United States)

    Heemels, M T; Ploegh, H L

    1994-12-01

    The transporter associated with antigen processing (TAP) translocates peptides from the cytosol into the lumen of the endoplasmic reticulum (ER). An important determinant for the specificity of translocation is the identity of the C-terminal residue of the peptide substrate. In the rat, a suitable C terminus is necessary but not always sufficient for a peptide to be selected for translocation. Here we show that sequence constraints within a peptide of optimal length (9 residues) may interfere with transport; that the transporter selectively translocates shorter derivatives of a 16-mer peptide rather than the 16-mer itself; and that the transporter cimb allele, which is most selective in the C termini it will tolerate, is more relaxed in peptide length preference than is the clma variant.

  8. Substrate specificity of allelic variants of the TAP peptide transporter.

    Science.gov (United States)

    Heemels, M T; Ploegh, H L

    1994-12-01

    The transporter associated with antigen processing (TAP) translocates peptides from the cytosol into the lumen of the endoplasmic reticulum (ER). An important determinant for the specificity of translocation is the identity of the C-terminal residue of the peptide substrate. In the rat, a suitable C terminus is necessary but not always sufficient for a peptide to be selected for translocation. Here we show that sequence constraints within a peptide of optimal length (9 residues) may interfere with transport; that the transporter selectively translocates shorter derivatives of a 16-mer peptide rather than the 16-mer itself; and that the transporter cimb allele, which is most selective in the C termini it will tolerate, is more relaxed in peptide length preference than is the clma variant. PMID:7895166

  9. New York State TrueAllele ® casework validation study.

    Science.gov (United States)

    Perlin, Mark W; Belrose, Jamie L; Duceman, Barry W

    2013-11-01

    DNA evidence can pose interpretation challenges, particularly with low-level or mixed samples. It would be desirable to make full use of the quantitative data, consider every genotype possibility, and objectively produce accurate and reproducible DNA match results. Probabilistic genotype computing is designed to achieve these goals. This validation study assessed TrueAllele(®) probabilistic computer interpretation on 368 evidence items in 41 test cases and compared the results with human review of the same data. Whenever there was a human result, the computer's genotype was concordant. Further, the computer produced a match statistic on 81 mixture items (for 87 inferred matching genotypes) in the test cases, while human review reported a statistic on 25 of these items (30.9%). Using match statistics to quantify information, probabilistic genotyping was shown to be sensitive, specific, and reproducible. These results demonstrate that objective probabilistic genotyping of biological evidence can reliably preserve DNA identification information.

  10. Introgressive hybridization: brown bears as vectors for polar bear alleles.

    Science.gov (United States)

    Hailer, Frank

    2015-03-01

    The dynamics and consequences of introgression can inform about numerous evolutionary processes. Biologists have therefore long been interested in hybridization. One challenge, however, lies in the identification of nonadmixed genotypes that can serve as a baseline for accurate quantification of admixture. In this issue of Molecular Ecology, Cahill et al. (2015) analyse a genomic data set of 28 polar bears, eight brown bears and one American black bear. Polar bear alleles are found to be introgressed into brown bears not only near a previously identified admixture zone on the Alaskan Admiralty, Baranof and Chichagof (ABC) Islands, but also far into the North American mainland. Elegantly contrasting admixture levels at autosomal and X chromosomal markers, Cahill and colleagues infer that male-biased dispersal has spread these introgressed alleles away from the Late Pleistocene contact zone. Compared to a previous study on the ABC Island population in which an Alaskan brown bear served as a putatively admixture-free reference, Cahill et al. (2015) utilize a newly sequenced Swedish brown bear as admixture baseline. This approach reveals that brown bears have been impacted by introgression from polar bears to a larger extent (up to 8.8% of their genome), than previously known, including the bear that had previously served as admixture baseline. No evidence for introgression of brown bear into polar bear is found, which the authors argue could be a consequence of selection. Besides adding new exciting pieces to the puzzle of polar/brown bear evolutionary history, the study by Cahill and colleagues highlights that wildlife genomics is moving from analysing single genomes towards a landscape genomics approach. PMID:25775930

  11. Radiographically visualized skeletal changes associated with mucopolysaccharidosis VI in cats

    International Nuclear Information System (INIS)

    The radiographic skeletal form and structure of all cats with mucopolysaccharidosis VI is described. Common manifestations included epiphyseal dysplasia, generalized osteoporosis, abnormal nasal turbinate development, his subluxation, impaired development of skeletal growth, pectus excavatum, hyoid hypoplasia, aplasia, hypoplasia and fragmentation or abnormal ossification of the dens, and aplasia or hypoplasia of frontal and sphenoid sinuses. The skeletal measurements of two affected cats were compared with those of normal, sex-matched littermates, and the measurements of two affected female cats were compared with those of a normal male littermate

  12. The Skeletally Immature and Newly Mature Throwing Athlete.

    Science.gov (United States)

    Braithwaite, Kiery A; Marshall, Kelley W

    2016-09-01

    Injuries to the shoulder and elbow in the pediatric and adolescent throwing athlete are common. Both knowledge of throwing mechanics and understanding of normal bone development in the immature skeleton are key to the diagnosis, treatment, and potential prevention of these common injuries. Pathologic changes from chronic repetitive trauma to the developing shoulder and elbow manifest as distinctly different injuries that can be predicted by the skeletal maturation of the patient. Sites of vulnerability and resulting patterns of injury change as the child evolves from the skeletally immature little league player to the skeletally mature high school/college athlete. PMID:27545423

  13. Bone-targeted agents: preventing skeletal complications in prostate cancer.

    Science.gov (United States)

    Morgans, Alicia K; Smith, Matthew R

    2012-11-01

    In men, prostate cancer is the most common non-cutaneous malignancy and the second most common cause of cancer death. Skeletal complications occur at various points during the disease course, either due to bone metastases directly, or as an unintended consequence of androgen deprivation therapy (ADT). Bone metastases are associated with pathologic fractures, spinal cord compression, and bone pain and can require narcotics or palliative radiation for pain relief. ADT results in bone loss and fragility fractures. This review describes the biology of bone metastases, skeletal morbidity, and recent advances in bone-targeted therapies to prevent skeletal complications of prostate cancer.

  14. Membranous lipodystrophy: skeletal findings on CT and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Nwawka, O.K.; Schneider, Robert; Mintz, Douglas N. [Hospital for Special Surgery, Department of Radiology and Imaging, New York, NY (United States); Bansal, Manjula [Hospital for Special Surgery, Department of Pathology and Laboratory Medicine, New York, NY (United States); Lane, Joseph [Hospital for Special Surgery, Department of Orthopedic Surgery, New York, NY (United States)

    2014-10-15

    Membranous lipodystrophy, also known as Nasu-Hakola disease, is a rare hereditary condition with manifestations in the nervous and skeletal systems. The radiographic appearance of skeletal lesions has been well described in the literature. However, CT and MRI findings of lesions in the bone have not been documented to date. This report describes the radiographic, CT, MRI, and histopathologic skeletal findings in a case of membranous lipodystrophy. With corroborative pathologic findings, a diagnosis of membranous lipodystrophy on imaging allows for appropriate clinical management of disease manifestations. (orig.)

  15. Membranous lipodystrophy: skeletal findings on CT and MRI.

    Science.gov (United States)

    Nwawka, O Kenechi; Schneider, Robert; Bansal, Manjula; Mintz, Douglas N; Lane, Joseph

    2014-10-01

    Membranous lipodystrophy, also known as Nasu-Hakola disease, is a rare hereditary condition with manifestations in the nervous and skeletal systems. The radiographic appearance of skeletal lesions has been well described in the literature. However, CT and MRI findings of lesions in the bone have not been documented to date. This report describes the radiographic, CT, MRI, and histopathologic skeletal findings in a case of membranous lipodystrophy. With corroborative pathologic findings, a diagnosis of membranous lipodystrophy on imaging allows for appropriate clinical management of disease manifestations.

  16. Generation of humoral immune responses to multi-allele PfAMA1 vaccines; effect of adjuvant and number of component alleles on the breadth of response.

    Directory of Open Access Journals (Sweden)

    Kwadwo A Kusi

    Full Text Available There is increasing interest in multi-allele vaccines to overcome strain-specificity against polymorphic vaccine targets such as Apical Membrane Antigen 1 (AMA1. These have been shown to induce broad inhibitory antibodies in vitro and formed the basis for the design of three Diversity-Covering (DiCo proteins with similar immunological effects. The antibodies produced are to epitopes that are shared between vaccine alleles and theoretically, increasing the number of component AMA1 alleles is expected to broaden the antibody response. A plateau effect could however impose a limit on the number of alleles needed to achieve the broadest specificity. Moreover, production cost and the vaccine formulation process would limit the number of component alleles. In this paper, we compare rabbit antibody responses elicited with multi-allele vaccines incorporating seven (three DiCos and four natural AMA1 alleles and three (DiCo mix antigens for gains in broadened specificity. We also investigate the effect of three adjuvant platforms on antigen specificity and antibody functionality. Our data confirms a broadened response after immunisation with DiCo mix in all three adjuvants. Higher antibody titres were elicited with either CoVaccine HT™ or Montanide ISA 51, resulting in similar in vitro inhibition (65-82% of five out of six culture-adapted P. falciparum strains. The antigen binding specificities of elicited antibodies were also similar and independent of the adjuvant used or the number of vaccine component alleles. Thus neither the four extra antigens nor adjuvant had any observable benefits with respect to specificity broadening, although adjuvant choice influenced the absolute antibody levels and thus the extent of parasite inhibition. Our data confirms the feasibility and potential of multi-allele PfAMA1 formulations, and highlights the need for adjuvants with improved antibody potentiation properties for AMA1-based vaccines.

  17. An Allele Real-Coded Quantum Evolutionary Algorithm Based on Hybrid Updating Strategy

    Directory of Open Access Journals (Sweden)

    Yu-Xian Zhang

    2016-01-01

    Full Text Available For improving convergence rate and preventing prematurity in quantum evolutionary algorithm, an allele real-coded quantum evolutionary algorithm based on hybrid updating strategy is presented. The real variables are coded with probability superposition of allele. A hybrid updating strategy balancing the global search and local search is presented in which the superior allele is defined. On the basis of superior allele and inferior allele, a guided evolutionary process as well as updating allele with variable scale contraction is adopted. And Hε gate is introduced to prevent prematurity. Furthermore, the global convergence of proposed algorithm is proved by Markov chain. Finally, the proposed algorithm is compared with genetic algorithm, quantum evolutionary algorithm, and double chains quantum genetic algorithm in solving continuous optimization problem, and the experimental results verify the advantages on convergence rate and search accuracy.

  18. An Allele Real-Coded Quantum Evolutionary Algorithm Based on Hybrid Updating Strategy.

    Science.gov (United States)

    Zhang, Yu-Xian; Qian, Xiao-Yi; Peng, Hui-Deng; Wang, Jian-Hui

    2016-01-01

    For improving convergence rate and preventing prematurity in quantum evolutionary algorithm, an allele real-coded quantum evolutionary algorithm based on hybrid updating strategy is presented. The real variables are coded with probability superposition of allele. A hybrid updating strategy balancing the global search and local search is presented in which the superior allele is defined. On the basis of superior allele and inferior allele, a guided evolutionary process as well as updating allele with variable scale contraction is adopted. And H ε gate is introduced to prevent prematurity. Furthermore, the global convergence of proposed algorithm is proved by Markov chain. Finally, the proposed algorithm is compared with genetic algorithm, quantum evolutionary algorithm, and double chains quantum genetic algorithm in solving continuous optimization problem, and the experimental results verify the advantages on convergence rate and search accuracy. PMID:27057159

  19. ApoE allele frequencies in Italian sporadic and familial Alzheimer's disease.

    Science.gov (United States)

    Sorbi, S; Nacmias, B; Forleo, P; Latorraca, S; Gobbini, I; Bracco, L; Piacentini, S; Amaducci, L

    1994-08-15

    Recent studies have provided evidence of association of apolipoprotein E (ApoE) epsilon 4 allele and late onset familial and sporadic Alzheimer's disease (AD). Epidemiological studies have established allelic variation at the ApoE locus. We have analyzed the ApoE gene polymorphism in a sample of 446 Italian subjects. Our data confirm a significant association between epsilon 4 allele and sporadic AD. The frequency of epsilon 4 allele in early onset familial AD patients was comparable to control values suggesting that epsilon 4 allele does not represent a risk factor for early onset familial AD (EOFAD). Moreover, we found a not previously reported association between ApoE epsilon 2 allele and sporadic AD and EOFAD. PMID:7824157

  20. Allelic diversity and molecular characterization of puroindoline genes in five diploid species of the Aegilops genus.

    Science.gov (United States)

    Cuesta, Susana; Guzmán, Carlos; Alvarez, Juan B

    2013-11-01

    Grain hardness is an important quality trait in wheat. This trait is related to the variation in, and the presence of, puroindolines (PINA and PINB). This variation can be increased by the allelic polymorphism present in the Aegilops species that are related to wheat. This study evaluated allelic Pina and Pinb gene variability in five diploid species of the Aegilops genus, along with the molecular characterization of the main allelic variants found in each species. This polymorphism resulted in 16 alleles for the Pina gene and 24 alleles for the Pinb gene, of which 10 and 17, respectively, were novel. Diverse mutations were detected in the deduced mature proteins of these alleles, which could influence the hardness characteristics of these proteins. This study shows that the diploid species of the Aegilops genus could be a good source of genetic variability for both Pina and Pinb genes, which could be used in breeding programmes to extend the range of different textures in wheat.

  1. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Timm, Sally; Wang, August G;

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission......-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  2. Enhancement of allele discrimination by introduction of nucleotide mismatches into siRNA in allele-specific gene silencing by RNAi.

    Directory of Open Access Journals (Sweden)

    Yusuke Ohnishi

    Full Text Available Allele-specific gene silencing by RNA interference (RNAi is therapeutically useful for specifically inhibiting the expression of disease-associated alleles without suppressing the expression of corresponding wild-type alleles. To realize such allele-specific RNAi (ASP-RNAi, the design and assessment of small interfering RNA (siRNA duplexes conferring ASP-RNAi is vital; however, it is also difficult. In a previous study, we developed an assay system to assess ASP-RNAi with mutant and wild-type reporter alleles encoding the Photinus and Renilla luciferase genes. In line with experiments using the system, we realized that it is necessary and important to enhance allele discrimination between mutant and corresponding wild-type alleles. Here, we describe the improvement of ASP-RNAi against mutant alleles carrying single nucleotide variations by introducing base substitutions into siRNA sequences, where original variations are present in the central position. Artificially mismatched siRNAs or short-hairpin RNAs (shRNAs against mutant alleles of the human Prion Protein (PRNP gene, which appear to be associated with susceptibility to prion diseases, were examined using this assessment system. The data indicates that introduction of a one-base mismatch into the siRNAs and shRNAs was able to enhance discrimination between the mutant and wild-type alleles. Interestingly, the introduced mismatches that conferred marked improvement in ASP-RNAi, appeared to be largely present in the guide siRNA elements, corresponding to the 'seed region' of microRNAs. Due to the essential role of the 'seed region' of microRNAs in their association with target RNAs, it is conceivable that disruption of the base-pairing interactions in the corresponding seed region, as well as the central position (involved in cleavage of target RNAs, of guide siRNA elements could influence allele discrimination. In addition, we also suggest that nucleotide mismatches at the 3'-ends of sense

  3. Stem Cell Separation Technologies

    OpenAIRE

    Zhu, Beili; Murthy, Shashi K

    2013-01-01

    Stem cell therapy and translational stem cell research require large-scale supply of stem cells at high purity and viability, thus leading to the development of stem cell separation technologies. This review covers key technologies being applied to stem cell separation, and also highlights exciting new approaches in this field. First, we will cover conventional separation methods that are commercially available and have been widely adapted. These methods include Fluorescence-activated cell so...

  4. [Separation anxiety. Theoretical considerations].

    Science.gov (United States)

    Blandin, N; Parquet, P J; Bailly, D

    1994-01-01

    The interest in separation anxiety is nowadays increasing: this disorder appearing during childhood may predispose to the occurrence of anxiety disorders (such as panic disorder and agoraphobia) and major depression into adulthood. Psychoanalytic theories differ on the nature of separation anxiety and its place in child development. For some authors, separation anxiety must be understood as resulting from the unconscious internal conflicts inherent in the individuation process and gradual attainment of autonomy. From this point of view, the fear of loss of mother by separation is not regarded as resulting from a real danger. However, Freud considers the primary experience of separation from protecting mother as the prototype situation of anxiety and compares the situations generating fear to separation experiences. For him, anxiety originates from two factors: the physiological fact is initiated at the time of birth but the primary traumatic situation is the separation from mother. This point of view may be compared with behavioral theories. Behavioral theories suggest that separation anxiety may be conditioned or learned from innate fears. In Freud's theory, the primary situation of anxiety resulting from the separation from mother plays a role comparable to innate fears. Grappling with the problem of separation anxiety, Bowlby emphasizes then the importance of the child's attachment to one person (mother or primary caregiver) and the fact that this attachment is instinctive. This point of view, based on the watch of infants, is akin to ethological theories on behaviour of non human primates. Bowlby especially shows that the reactions of infant separated from mother evolve on three stages: the phase of protestation which may constitute the prototype of adulthood anxiety, the phase of desperation which may be the prototype of depression, and the phase of detachment. He emphasizes so the role of early separations in the development of vulnerability to depression

  5. Age of an allele and gene genealogies of nested subsamples for populations admitting large offspring numbers

    OpenAIRE

    Eldon, Bjarki

    2012-01-01

    Coalescent processes, including mutation, are derived from Moran type population models admitting large offspring numbers. Including mutation in the coalescent process allows for quantifying the turnover of alleles by computing the distribution of the number of original alleles still segregating in the population at a given time in the past. The turnover of alleles is considered for specific classes of the Moran model admitting large offspring numbers. Versions of the Kingman coalescent are a...

  6. Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase

    OpenAIRE

    Carney, Amanda E.; Rebecca D Sanders; Garza, Kerry R.; McGaha, Lee Anne; Bean, Lora J. H.; Coffee, Bradford W.; Thomas, James W; Cutler, David J.; Kurtkaya, Natalie L.; Fridovich-Keil, Judith L.

    2009-01-01

    Duarte galactosemia is a mild to asymptomatic condition that results from partial impairment of galactose-1-phosphate uridylyltransferase (GALT). Patients with Duarte galactosemia demonstrate reduced GALT activity and carry one profoundly impaired GALT allele (G) along with a second, partially impaired GALT allele (Duarte-2, D2). Molecular studies reveal at least five sequence changes on D2 alleles: a p.N314D missense substitution, three intronic base changes and a 4 bp deletion in the 5′ pro...

  7. Identification of resistant carboxylesterase alleles in Culex pipiens complex via PCR-RFLP

    Directory of Open Access Journals (Sweden)

    Zhang Hanying

    2012-09-01

    Full Text Available Abstract Background Carboxylesterase overproduction is a frequently observed resistance mechanism of insects to organophosphate insecticides. As a major transmitter of human diseases, mosquitoes in the Culex pipiens complex have evolved 13 carboxylesterase alleles (Ester that confer organophosphate resistance. Six alleles, EsterB1, Ester2, Ester8, Ester9, EsterB10, and Ester11, have been observed in field populations in China, sometimes co-existing in one population. To differentiate the carboxylesterase alleles found in these field populations, PCR-RFLP was designed for use in resistance monitoring. Results Based on the DNA sequences of resistant and nonresistant carboxylesterase alleles, Ester B alleles were first amplified with PCR-specific primers and then digested with the restriction enzyme DraI. In this step, Ester2 and Ester11 were differentiated from the other Ester alleles. When the other Ester B alleles were digested with the restriction enzyme XbaI, EsterB1 and the susceptible C. p. pallens Ester were screened out. Ester8 and Ester9 were differentiated from EsterB10 and the susceptible C. p. quinquefasciatus esterase allele, respectively, by amplifying and digesting the Ester A alleles with the restriction enzyme ApaLI. The effectiveness of the custom-designed PCR-RFLP was verified in two field mosquito populations. Conclusions A PCR-RFLP based approach was developed to differentiate carboxylesterase alleles in Culex pipiens complex mosquitoes. These processes may be useful in monitoring the evolutionary dynamics of known carboxylesterase alleles as well as in the identification of new alleles in field populations.

  8. Separation of flow

    CERN Document Server

    Chang, Paul K

    2014-01-01

    Interdisciplinary and Advanced Topics in Science and Engineering, Volume 3: Separation of Flow presents the problem of the separation of fluid flow. This book provides information covering the fields of basic physical processes, analyses, and experiments concerning flow separation.Organized into 12 chapters, this volume begins with an overview of the flow separation on the body surface as discusses in various classical examples. This text then examines the analytical and experimental results of the laminar boundary layer of steady, two-dimensional flows in the subsonic speed range. Other chapt

  9. Entrainment separator performance

    International Nuclear Information System (INIS)

    Clean and dust-loaded ACS entrainment separators mounted upstream of HEPA filters were exposed to a combination of fine water mist and steam at about 700C from one to four hours. In every trial, the ACS entrainment separator prevented measurable deterioration of performance in the following HEPA filter. Droplet size-efficiency evaluation of the ACS entrainment separators showed that, within the accuracy of the measurements, they meet all service requirements and are fully equal to the best separator units available for service on pressurized water reactors

  10. Persistence of the common Hartnup disease D173N allele in populations of European origin.

    Science.gov (United States)

    Azmanov, Dimitar N; Rodgers, Helen; Auray-Blais, Christiane; Giguère, Robert; Bailey, Charles; Bröer, Stefan; Rasko, John E J; Cavanaugh, Juleen A

    2007-11-01

    Hartnup disorder is an aminoaciduria that results from mutations in the recently described gene SLC6A19 on chromosome 5p15.33. The disease is inherited in a simple recessive manner and ten different mutations have been described to date. One mutation, the D173N allele, is present in 42% of Hartnup chromosomes from apparently unrelated families from both Australia and North America. We report an investigation of the origins of the D173N allele using a unique combination of variants including SNPs, microsatellites, and a VNTR across 211 Kb spanning the SLC6A19 locus. All individuals who carry the mutant allele share an identical core haplotype suggesting a single common ancestor, indicating that the elevated frequency of the D173N allele is not a result of recurrent mutation. Analyses of these data indicate that the allele is more than 1000 years old. We compare the reasons for survival of this allele with other major alleles in some other common autosomal recessive diseases occurring in European Caucasians. We postulate that survival of this allele may be a consequence of failure of the allele to completely inactivate the transport of neutral amino acids. PMID:17555458

  11. Sequence analysis of two de novo mutation alleles at the DXS10011 locus.

    Science.gov (United States)

    Tamura, Akiyoshi; Iwata, Misa; Takase, Izumi; Miyazaki, Tokiko; Matsui, Kiyoshi; Nishio, Hajime; Suzuki, Koichi

    2003-09-01

    We have detected two unusual alleles at the DXS10011 locus in two paternity trio cases. In one case, one allele of the daughter was found not to have been derived from the mother but the other allele was shared with the father. In the other case, the mother and the son shared no bands. Paternity in both cases was established using conventional polymorphic markers in addition to DNA markers (probabilities: >0.999999). Sequencing showed that the two de novo alleles of the children acquired a single unit (GAAA).

  12. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, H.B.; Timm, S.; Wang, A.G.;

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  13. Allele-specific enzymatic amplification of beta-globin genomic DNA for diagnosis of sickle cell anemia.

    OpenAIRE

    Wu, D Y; Ugozzoli, L; B..K. Pal; Wallace, R B

    1989-01-01

    A rapid nonradioactive approach to the diagnosis of sickle cell anemia is described based on an allele-specific polymerase chain reaction (ASPCR). This method allows direct detection of the normal or the sickle cell beta-globin allele in genomic DNA without additional steps of probe hybridization, ligation, or restriction enzyme cleavage. Two allele-specific oligonucleotide primers, one specific for the sickle cell allele and one specific for the normal allele, together with another primer co...

  14. Orthodontics-surgical combination therapy for Class III skeletal malocclusion

    Directory of Open Access Journals (Sweden)

    M S Ravi

    2012-01-01

    Full Text Available The correction of skeletal Class III malocclusion with severe mandibular prognathism in an adult individual requires surgical and Othodontic combination therapy. The inter disciplinary approach is the treatment of choice in most of the skeletal malocclusions. A case report of an adult individual with Class III malocclusion, having mandibular excess in sagittal and vertical plane and treated with orthodontics,, bilateral sagittal split osteotomy and Le - Forte I osteotomy for the correction of skeletal, dental and soft tissue discrepancies is herewith presented. The surgical-orthodontic combination therapy has resulted in near-normal skeletal, dental and soft tissue relationship, with marked improvement in the facial esthetics in turn, has helped the patient to improve the self-confidence level.

  15. Arginylation of Myosin Heavy Chain Regulates Skeletal Muscle Strength

    Directory of Open Access Journals (Sweden)

    Anabelle S. Cornachione

    2014-07-01

    Full Text Available Protein arginylation is a posttranslational modification with an emerging global role in the regulation of actin cytoskeleton. To test the role of arginylation in the skeletal muscle, we generated a mouse model with Ate1 deletion driven by the skeletal muscle-specific creatine kinase (Ckmm promoter. Ckmm-Ate1 mice were viable and outwardly normal; however, their skeletal muscle strength was significantly reduced in comparison to controls. Mass spectrometry of isolated skeletal myofibrils showed a limited set of proteins, including myosin heavy chain, arginylated on specific sites. Atomic force microscopy measurements of contractile strength in individual myofibrils and isolated myosin filaments from these mice showed a significant reduction of contractile forces, which, in the case of myosin filaments, could be fully rescued by rearginylation with purified Ate1. Our results demonstrate that arginylation regulates force production in muscle and exerts a direct effect on muscle strength through arginylation of myosin.

  16. Suspected fetal skeletal malformations or bone diseases: how to explore

    Energy Technology Data Exchange (ETDEWEB)

    Cassart, Marie [Erasme Hospital, Medical Imaging, Brussels (Belgium)

    2010-06-15

    Skeletal dysplasias are a heterogeneous and complex group of conditions that affect bone growth and development and result in various anomalies in shape and size of the skeleton. Although US has proved reliable for the prenatal detection of skeletal abnormalities, the precise diagnosis of a dysplasia is often difficult to make before birth (especially in the absence of a familial history) due to their various phenotypic presentations, the variability in the time at which they manifest and often, the lack of precise molecular diagnosis. In addition to the accuracy of the antenatal diagnosis, it is very important to establish a prognosis. This is a clinically relevant issue as skeletal dysplasias may be associated with severe disability and may even be lethal. We will therefore describe the respective role of two-dimensional (2-D) US, three-dimensional (3-D) US and CT in the antenatal assessment of skeletal malformations. (orig.)

  17. Skeletal metastasis: treatments, mouse models,and the Wnt signaling

    Institute of Scientific and Technical Information of China (English)

    Kenneth C.Valkenburg; Matthew R.Steensma; Bart O.Williams; Zhendong Zhong

    2013-01-01

    Skeletal metastases result in significant morbidity and mortality.This is particularly true of cancers with a strong predilection for the bone,such as breast,prostate,and lung cancers.There is currently no reliable cure for skeletal metastasis,and palliative therapy options are limited.The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target.Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments.In this review,we discuss pathologic process of bone metastasis,the roles of the Wnt signaling,and the available experimental models and treatments.

  18. Regulation of the skeletal muscle blood flow in humans

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Saltin, Bengt

    2014-01-01

    In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... sympathetic vasoconstriction. ATP is released into plasma from erythrocytes and endothelial cells and the plasma concentration increases in both the feeding artery and the vein draining the contracting skeletal muscle. Adenosine also stimulates the formation of NO and prostaglandins, but the plasma adenosine...... concentration does not increase during exercise. In the skeletal muscle interstitium, there is a marked increase in the concentration of ATP and adenosine and this increase is tightly coupled to the increase in blood flow. The sources of interstitial ATP and adenosine are thought to be skeletal muscle cells...

  19. Purinergic receptors expressed in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Bornø, A; Ploug, Thorkil; Bune, L T;

    2012-01-01

    distribution of purinergic receptors in skeletal muscle fibres. We speculate that the intracellular localization of purinergic receptors may reflect a role in regulation of muscle metabolism; further studies are nevertheless needed to determine the function of the purinergic system in skeletal muscle cells.......Purinergic receptors are present in most tissues and thought to be involved in various signalling pathways, including neural signalling, cell metabolism and local regulation of the microcirculation in skeletal muscles. The present study aims to determine the distribution and intracellular content...... of purinergic receptors in skeletal muscle fibres in patients with type 2 diabetes and age-matched controls. Muscle biopsies from vastus lateralis were obtained from six type 2 diabetic patients and seven age-matched controls. Purinergic receptors were analysed using light and confocal microscopy...

  20. Is skeletal anchorage changing the limit of orthodontics?

    DEFF Research Database (Denmark)

    Melsen, Birte

    2007-01-01

    The limits for orthodontic treatment are often set by the lack of suitable anchorage. The mini-implant is used where conventional anchorage cannot be applied; not as a replacement for conventional anchorage. In patients with lack of teeth and reduced periodontium, skeletal anchorage allows...... and can be loaded immediately. The course will be addressed the following topics: Are the mini-implants replacing conventional anchorage? Why are orthodontic mini-implants necessary? The development of the skeletal anchorage systems The biological basis for the skeletal anchorage systems...... The characteristics of the different skeletal anchorage systems The insertion procedure The indications for the use of orthodontic mini-implants Treatment planning in relation to the use of mini-implants Case presentations...

  1. Regulation of PDH, GS and insulin signalling in skeletal muscle

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup

    The aims of the present thesis were to investigate 1) The impact of physical inactivity on insulinstimulated Akt, TBC1D4 and GS regulation in human skeletal muscle, 2) The impact of exercise training on glucose-mediated regulation of PDH and GS in skeletal muscle in elderly men, 3) The impact...... of inflammation on resting and exercise-induced PDH regulation in human skeletal muscle and 4) The effect of IL-6 on PDH regulation in mouse skeletal muscle. Study I demonstrated that bed rest–induced insulin resistance was associated with reduced insulinstimulated GS activity and Akt signaling as well...... glucose to the level seen when exercise was performed before bed rest. Study II demonstrated that exercise training-improved glucose regulation in elderly healthy subjects was associated with increased HKII, GLUT4, Akt2, PDK2, GS and PDH-E1α protein content. Moreover, exercise training resulted...

  2. The separation of adult separation anxiety disorder.

    Science.gov (United States)

    Baldwin, David S; Gordon, Robert; Abelli, Marianna; Pini, Stefano

    2016-08-01

    The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) categorization of mental disorders places "separation anxiety disorder" within the broad group of anxiety disorders, and its diagnosis no longer rests on establishing an onset during childhood or adolescence. In previous editions of DSM, it was included within the disorders usually first diagnosed in infancy, childhood, or adolescence, with the requirement for an onset of symptoms before the age of 18 years: symptomatic adults could only receive a retrospective diagnosis, based on establishing this early onset. The new position of separation anxiety disorder is based upon the findings of epidemiological studies that revealed the unexpectedly high prevalence of the condition in adults, often in individuals with an onset of symptoms after the teenage years; its prominent place within the DSM-5 group of anxiety disorders should encourage further research into its epidemiology, etiology, and treatment. This review examines the clinical features and boundaries of the condition, and offers guidance on how it can be distinguished from other anxiety disorders and other mental disorders in which "separation anxiety" may be apparent.

  3. The separation of adult separation anxiety disorder.

    Science.gov (United States)

    Baldwin, David S; Gordon, Robert; Abelli, Marianna; Pini, Stefano

    2016-08-01

    The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) categorization of mental disorders places "separation anxiety disorder" within the broad group of anxiety disorders, and its diagnosis no longer rests on establishing an onset during childhood or adolescence. In previous editions of DSM, it was included within the disorders usually first diagnosed in infancy, childhood, or adolescence, with the requirement for an onset of symptoms before the age of 18 years: symptomatic adults could only receive a retrospective diagnosis, based on establishing this early onset. The new position of separation anxiety disorder is based upon the findings of epidemiological studies that revealed the unexpectedly high prevalence of the condition in adults, often in individuals with an onset of symptoms after the teenage years; its prominent place within the DSM-5 group of anxiety disorders should encourage further research into its epidemiology, etiology, and treatment. This review examines the clinical features and boundaries of the condition, and offers guidance on how it can be distinguished from other anxiety disorders and other mental disorders in which "separation anxiety" may be apparent. PMID:27503572

  4. Resistance Exercise Reverses Aging in Human Skeletal Muscle

    OpenAIRE

    Simon Melov; Tarnopolsky, Mark A.; Kenneth Beckman; Krysta Felkey; Alan Hubbard

    2007-01-01

    Human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia). Multiple lines of evidence suggest that mitochondrial dysfunction is a major contributor to sarcopenia. We evaluated whether healthy aging was associated with a transcriptional profile reflecting mitochondrial impairment and whether resistance exercise could reverse this signature to that approximating a younger physiological age. Skeletal muscle biopsies from healthy older (N = 25) and younger (N =...

  5. Caries prevalence in skeletal series: is it possible to compare?

    OpenAIRE

    Veronica Wesolowski

    2006-01-01

    Because of the relationship with subsistence, dental caries is a central issue in paleopathological research. Usually, comparisons between caries prevalence exhibited in different skeletal series are made. Dietary variation is the most common explanation for cavities prevalence. The aim of this paper is to verify if it is possible to compare caries prevalence reported on papers for archaeological skeletal series. Another goal is to determine if other factors besides diet are implicated in den...

  6. Mechanistic and therapeutic insights gained from studying rare skeletal diseases.

    Science.gov (United States)

    Tosi, Laura L; Warman, Matthew L

    2015-07-01

    Rare bone diseases account for 5% of all birth defects and can cause significant morbidity throughout patients' lives. Significant progress is being made to elucidate the pathophysiological mechanisms underlying these diseases. This paper summarizes presentation highlights of a workshop on Rare Skeletal Diseases convened to explore how the study of rare diseases has influenced the field's understanding of bone anabolism and catabolism and directed the search for new therapies benefiting patients with rare conditions as well as patients with common skeletal disorders.

  7. Nutritional components affecting skeletal development in fish larvae

    OpenAIRE

    Cahu, Chantal; Zambonino, Jose-luis; Takeuchi, Toshio

    2003-01-01

    Marine fish larvae undergo major functional and morphological changes during the developmental stages and several factors can interfere with the normal development of larvae and affect fry quality. Skeletal malformations, such as spinal malformation-scoliosis, lordosis, coiled vertebral column-, missing or additional fin rays, bending opercle or jaw malformations, are frequently observed in hatchery-reared larvae. This paper reviews the effects of some nutritional components on skeletal devel...

  8. Orthodontics-surgical combination therapy for Class III skeletal malocclusion

    OpenAIRE

    Ravi, M. S.; Nillan K Shetty; Prasad, Rajendra B.

    2012-01-01

    The correction of skeletal Class III malocclusion with severe mandibular prognathism in an adult individual requires surgical and Othodontic combination therapy. The inter disciplinary approach is the treatment of choice in most of the skeletal malocclusions. A case report of an adult individual with Class III malocclusion, having mandibular excess in sagittal and vertical plane and treated with orthodontics,, bilateral sagittal split osteotomy and Le - Forte I osteotomy for the correction of...

  9. Development and progress of engineering of skeletal muscle tissue

    OpenAIRE

    Zhou, GQ; Liao, H.

    2009-01-01

    Engineering skeletal muscle tissue remains still a challenge, and numerous studies have indicated that this technique may be of great importance in medicine in the near future. This article reviews some of the recent findings resulting from tissue engineering science related to the contractile behavior and the phenotypes of muscle tissue cells in different three-dimensional environment, and discusses how tissue engineering could be used to create and regenerate skeletal muscle, as well as the...

  10. Effect of ionizing radiation on human skeletal muscle precursor cells

    OpenAIRE

    Marš, Tomaž; Čemažar, Maja; Jurdana, Mihaela; Pegan, Katarina

    2015-01-01

    Background. Long term effects of different doses of ionizing radiation on human skeletal muscle myoblast proliferation, cytokine signalling and stress response capacity were studied in primary cell cultures.Materials and methods. Human skeletal muscle myoblasts obtained from muscle biopsies were cultured and irradiated with a Darpac 2000 X-ray unit at doses of 4, 6 and 8 Gy. Acute effects of radiation were studied by interleukin - 6 (IL-6) release and stress response detected by the heat shoc...

  11. Adiponectin Upregulates Ferritin Heavy Chain in Skeletal Muscle Cells

    OpenAIRE

    Ikegami, Yuichi; Inukai, Kouichi; Imai, Kenta; Sakamoto, Yasushi; Katagiri, Hideki; Kurihara, Susumu; Awata, Takuya; Katayama, Shigehiro

    2009-01-01

    OBJECTIVE—Adiponectin is an adipocyte-derived protein that acts to reduce insulin resistance in the liver and muscle and also inhibits atherosclerosis. Although adiponectin reportedly enhances AMP-activated protein kinase and inhibits tumor necrosis factor-α action downstream from the adiponectin signal, the precise physiological mechanisms by which adiponectin acts on skeletal muscles remain unknown. RESEARCH DESIGN AND METHODS—We treated murine primary skeletal muscle cells with recombinant...

  12. Skeletal muscle microvascular function in girls with Turner syndrome

    OpenAIRE

    West, Sarah L.; Clodagh S. O'Gorman; Elzibak, Alyaa H.; Jessica Caterini; Noseworthy, Michael D.; Tammy Rayner; Jill Hamilton; Wells, Greg D

    2015-01-01

    Background: Exercise intolerance is prevalent in individuals with Turner Syndrome (TS). We recently demonstrated that girls with TS have normal aerobic but altered skeletal muscle anaerobic metabolism compared to healthy controls (HC). The purpose of this study was to compare peripheral skeletal muscle microvascular function in girls with TS to HC after exercise. We hypothesized that girls with TS would have similar muscle blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) s...

  13. Natriuretic peptides enhance the oxidative capacity of human skeletal muscle

    OpenAIRE

    Engeli, Stefan; Birkenfeld, Andreas L.; Badin, Pierre-Marie; Bourlier, Virginie; Louche, Katie; Viguerie, Nathalie; Thalamas, Claire; Montastier, Emilie; Larrouy, Dominique; Harant, Isabelle; de Glisezinski, Isabelle; Lieske, Stefanie; Reinke, Julia; Beckmann, Bibiana; Langin, Dominique

    2012-01-01

    Cardiac natriuretic peptides (NP) are major activators of human fat cell lipolysis and have recently been shown to control brown fat thermogenesis. Here, we investigated the physiological role of NP on the oxidative metabolism of human skeletal muscle. NP receptor type A (NPRA) gene expression was positively correlated to mRNA levels of PPARγ coactivator-1α (PGC1A) and several oxidative phosphorylation (OXPHOS) genes in human skeletal muscle. Further, the expression of NPRA, PGC1A, and OXPHOS...

  14. Dysregulation of skeletal muscle protein metabolism by alcohol

    OpenAIRE

    Steiner, Jennifer L.; Lang, Charles H.

    2015-01-01

    Alcohol abuse, either by acute intoxication or prolonged excessive consumption, leads to pathological changes in many organs and tissues including skeletal muscle. As muscle protein serves not only a contractile function but also as a metabolic reserve for amino acids, which are used to support the energy needs of other tissues, its content is tightly regulated and dynamic. This review focuses on the etiology by which alcohol perturbs skeletal muscle protein balance and thereby over time prod...

  15. Mesenchymal stem cells (MSCs) as skeletal therapeutics–an update

    OpenAIRE

    Saeed, Hamid; Ahsan, Muhammad; Saleem, Zikria; Iqtedar, Mehwish; Islam, Muhammad; Danish, Zeeshan; Khan, Asif Manzoor

    2016-01-01

    Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair/regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/ser...

  16. Mechanobiology of Embryonic Skeletal Development: Insights from Animal Models

    OpenAIRE

    Nowlan, Niamh C.; Sharpe, James; Karen A Roddy; Prendergast, Patrick J; Murphy, Paula

    2010-01-01

    A range of clinical conditions in which foetal movement is reduced or prevented can have a severe effect on skeletal development. Animal models have been instrumental to our understanding of the interplay between mechanical forces and skeletal development, in particular the mouse and the chick model systems. In the chick, the most commonly used means of altering the mechanical environment is by pharmaceutical agents which induce paralysis, while genetically modified mice with non-functional o...

  17. Eccentric Exercise Facilitates Mesenchymal Stem Cell Appearance in Skeletal Muscle

    OpenAIRE

    M Carmen Valero; Huntsman, Heather D.; Jianming Liu; Kai Zou; Boppart, Marni D.

    2012-01-01

    Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1) positive, non-hemat...

  18. Real time ray tracing of skeletal implicit surfaces

    DEFF Research Database (Denmark)

    Rouiller, Olivier; Bærentzen, Jakob Andreas

    Modeling and rendering in real time is usually done via rasterization of polygonal meshes. We present a method to model with skeletal implicit surfaces and an algorithm to ray trace these surfaces in real time in the GPU. Our skeletal representation of the surfaces allows to create smooth models...... easily that can be seamlessly animated and textured. The ray tracing is performed at interactive frame rate thanks to an acceleration data structure based on a BVH and a kd-tree....

  19. COX-2 inhibitor reduces skeletal muscle hypertrophy in mice

    OpenAIRE

    Novak, Margaret L.; Billich, William; Smith, Sierra M.; Sukhija, Kunal B.; McLoughlin, Thomas J.; Hornberger, Troy A.; Timothy J. Koh

    2009-01-01

    Anti-inflammatory strategies are often used to reduce muscle pain and soreness that can result from high-intensity muscular activity. However, studies indicate that components of the acute inflammatory response may be required for muscle repair and growth. The hypothesis of this study was that cyclooxygenase (COX)-2 activity is required for compensatory hypertrophy of skeletal muscle. We used the synergist ablation model of skeletal muscle hypertrophy, along with the specific C...

  20. Skeletal Muscle Stem Cells from Animals I. Basic Cell Biology

    OpenAIRE

    Michael V. Dodson, Gary J. Hausman, LeLuo Guan, Min Du, Theodore P. Rasmussen, Sylvia P. Poulos, Priya Mir, Werner G. Bergen, Melinda E. Fernyhough, Douglas C. McFarland, Robert P. Rhoads, Beatrice Soret, James M. Reecy, Sandra G. Velleman, Zhihua Jiang

    2010-01-01

    Skeletal muscle stem cells from food-producing animals are of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding of muscle stem cell biology and function is essential for developing technologies and strategies to augment the metabolic efficiency and muscle hypertrophy of growing animals potentially leading to grea...

  1. Skeletal muscle digoxin binding in patients with renal failure.

    OpenAIRE

    Jogestrand, T; Ericsson, F

    1983-01-01

    For digoxin analyses blood and skeletal muscle samples were taken from seven digoxin-treated patients with chronic renal failure. The ratio between skeletal muscle and serum digoxin concentration in the patients with renal failure was not significantly different from the ratios in two control groups consisting of subjects with normal renal function. In the group of patients with renal failure there was no relationship between the glomerular filtration rate and muscle digoxin binding (specific...

  2. AMPK Control of Fat Metabolism in Skeletal Muscle

    OpenAIRE

    Thomson, David M.; Winder, William W.

    2009-01-01

    AMP-activated protein kinase (AMPK) has emerged as a key regulator of skeletal muscle fat metabolism. Because abnormalities in skeletal muscle metabolism contribute to a variety of clinical diseases and disorders, understanding AMPK’s role in the muscle is important. It was originally shown to stimulate fatty acid oxidation decades ago, and since then much research has been accomplished describing this role. In this brief review we summarize much of this data, particularly in relation to chan...

  3. Road to Exercise Mimetics: Targeting Nuclear Receptors in Skeletal Muscle

    OpenAIRE

    Fan, Weiwei; Atkins, Annette R.; Yu, Ruth T.; Downes, Michael; Ronald M. Evans

    2013-01-01

    Skeletal muscle comprises the largest organ in the human body and is the major site for energy expenditure. It exhibits remarkable plasticity in response to physiological stimuli such as exercise. Physical exercise remodels skeletal muscle and enhances its capability to burn calories, which has been shown to be beneficial for many clinical conditions including metabolic syndrome and cancer. Nuclear receptors (NRs) comprise a class of transcription factors found only in metazoans that regulate...

  4. Skeletal muscle matrix metalloproteinase and exercise in humans

    OpenAIRE

    Rullman, Eric

    2011-01-01

    Skeletal muscle is a highly plastic tissue; it has a great capacity to adapt to environmental demands throughout life. The structural and functional changes that occur in response to exercise training are well characterized whereas much less is known about these adaptive processes at the cellular and molecular levels. A possibly underestimated aspect of skeletal muscle adaptation to exercise is the remodeling of the extracellular matrix (ECM). Degradation and processing of...

  5. DNA TYPING FOR HLA - DR ALLELES BY PCR - AMPLIFICATION WITH SEQUENCE- SPECIFIC PRIMERS

    Institute of Scientific and Technical Information of China (English)

    谭建明; 谢桐; 徐琴君

    1999-01-01

    Ohjective To establish a rapid genetyping for HLA- DR alleles by polymerase chain reaction wiht sequence - specifie primers (PCR - SSP) for clinical application. Material and Methods The subjects of study included 69 recipients, 43 unrelated donors and 5 cell lines, Genomic DNA was prepared from peripheral blood leukoeytes by a salting- out method, Thirty primers designed according to the HLA- DRB nucleotide sequences, and synthesized on a 391 DNN synthesizer,Twenty separate PCR reactions were perfomed for each sample, The amplification was accomplished by 34 cycles consisting of denaturation at 94℃ for 30 seconds, annealing at 60℃ for 50 seconds and extension at 72℃ for 40 seconds The specificity of matching was determined by standard DNAs and Southem hybeidization using DIG labeling probes. Results All 112 samples and 5 cell lines were able to be typed by PCR-SSP,No false positive or false negative typing results were obtained. The reproducibility was 100 %,The size of the .specific product was in cnoccrdance with the size of the designed primers. The overall time for genotyping was 4 bours. The typing results were confirned by Southem hybridization.Conelusions Genotyping for HLA- DR by PCR- SSP is a rapid and accurate matching technique suited for clinical application.

  6. Method for separating isotopes

    Science.gov (United States)

    Jepson, B.E.

    1975-10-21

    Isotopes are separated by contacting a feed solution containing the isotopes with a cyclic polyether wherein a complex of one isotope is formed with the cyclic polyether, the cyclic polyether complex is extracted from the feed solution, and the isotope is thereafter separated from the cyclic polyether.

  7. Nonterminal Separating Macro Grammars

    NARCIS (Netherlands)

    Hogendorp, Jan Anne; Asveld, P.R.J.; Nijholt, A.; Verbeek, Leo A.M.

    1987-01-01

    We extend the concept of nonterminal separating (or NTS) context-free grammar to nonterminal separating $m$-macro grammar where the mode of derivation $m$ is equal to "unrestricted". "outside-in' or "inside-out". Then we show some (partial) characterization results for these NTS $m$-macro grammars.

  8. Social Separation in Monkeys.

    Science.gov (United States)

    Mineka, Susan; Suomi, Stephen J.

    1978-01-01

    Reviews phenomena associated with social separation from attachment objects in nonhuman primates. Evaluates four theoretical treatments of separation in light of existing data: Bowlby's attachment-object-loss theory, Kaufman's conservation-withdrawal theory, Seligman's learned helplessness theory, and Solomon and Corbit's opponent-process theory.…

  9. Imprinted chromosomal domains revealed by allele-specific replication timing of the GABRB3 and GABRA5 genes

    Energy Technology Data Exchange (ETDEWEB)

    LaSalle, J.; Flint, A.; Lalande, M. [Harvard Medical School, Boston, MA (United States)] [and others

    1994-09-01

    The GABRB3 and GABRA5 genes are organized as a cluster in chromosome 15q11-q13. The genes are separated by around 100 kb and arranged in opposite transcriptional orientations. The GABA{sub A} receptor cluster lies near the Angelman and Prader-Willi loci and displays asynchronous DNA replication, suggesting that this region is subject to parental imprinting. In order to further study the association between DNA replication and imprinting, allele-specific replication was assayed by fluorescence in situ hybridization with {lambda}-phage probes from the GABRB3/A5 region and a D15Z1 satellite probe to identify the parental origin of each chromosome. The replication kinetics of each allele was determined by using a flow sorter to fractionate mitogen-stimulated lymphocytes on the basis of cell cycle progression prior to FISH analysis. These kinetic studies reveal a 50-150 kb chromosomal domain extending from the middle of the GABRB3/A5 intergenic region into the GABRA5 5{prime}-UTR which displays maternal replication in early S with paternal replication delayed until the end of S. In contrast, genomic regions on either side of this maternal early replication domain exhibit the opposite pattern with paternal before maternal replication and both alleles replicating in the latter half of S. These results indicate that the GABRB3/A5 region is divided into domains in which replication timing is determined by parental origin. In addition to a loss of asynchronous replication, organization into replication timing domains is also lost in lymphocytes from maternal and paternal uniparental disomy 15 patients suggesting that a chromosome contribution from both parents is required for the establishment of the imprinted replication domains.

  10. Separators for flywheel rotors

    Science.gov (United States)

    Bender, Donald A.; Kuklo, Thomas C.

    1998-01-01

    A separator forms a connection between the rotors of a concentric rotor assembly. This separator allows for the relatively free expansion of outer rotors away from inner rotors while providing a connection between the rotors that is strong enough to prevent disassembly. The rotor assembly includes at least two rotors referred to as inner and outer flywheel rings or rotors. This combination of inner flywheel ring, separator, and outer flywheel ring may be nested to include an arbitrary number of concentric rings. The separator may be a segmented or continuous ring that abuts the ends of the inner rotor and the inner bore of the outer rotor. It is supported against centrifugal loads by the outer rotor and is affixed to the outer rotor. The separator is allowed to slide with respect to the inner rotor. It is made of a material that has a modulus of elasticity that is lower than that of the rotors.

  11. Disagreement in genotyping results of drug resistance alleles of the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) gene by allele-specific PCR (ASPCR) assays and Sanger sequencing.

    Science.gov (United States)

    Sharma, Divya; Lather, Manila; Dykes, Cherry L; Dang, Amita S; Adak, Tridibes; Singh, Om P

    2016-01-01

    The rapid spread of antimalarial drug resistance in Plasmodium falciparum over the past few decades has necessitated intensive monitoring of such resistance for an effective malaria control strategy. P. falciparum dihydropteroate synthase (Pfdhps) and P. falciparum dihydrofolate reductase (Pfdhfr) genes act as molecular markers for resistance against the antimalarial drugs sulphadoxine and pyrimethamine, respectively. Resistance to pyrimethamine which is used as a partner drug in artemisinin combination therapy (ACT) is associated with several mutations in the Pfdhfr gene, namely A16V, N51I, C59R, S108N/T and I164L. Therefore, routine monitoring of Pfdhfr-drug-resistant alleles in a population may help in effective drug resistance management. Allele-specific PCR (ASPCR) is one of the commonly used methods for molecular genotyping of these alleles. In this study, we genotyped 55 samples of P. falciparum for allele discrimination at four codons of Pfdhfr (N51, C59, S108 and I164) by ASPCR using published methods and by Sanger's DNA sequencing method. We found that the ASPCR identified a significantly higher number of mutant alleles as compared to the DNA sequencing method. Such discrepancies arise due to the non-specificity of some of the allele-specific primer sets and due to the lack of sensitivity of Sanger's DNA sequencing method to detect minor alleles present in multiple clone infections. This study reveals the need of a highly specific and sensitive method for genotyping and detecting minor drug-resistant alleles present in multiple clonal infections.

  12. Zebrafish Fins as a Model System for Skeletal Human Studies

    Directory of Open Access Journals (Sweden)

    Manuel Marí-Beffa

    2007-01-01

    Full Text Available Recent studies on the morphogenesis of the fins of Danio rerio (zebrafish during development and regeneration suggest that a number of inductive signals involved in the process are similar to some of those that affect bone and cartilage differentiation in mammals and humans. Akimenko et al. (2002 has shown that bone morphogenetic protein-2b (BMP2b is involved in the induction of dermal bone differentiation during fin regeneration. Many other groups have also shown that molecules from the transforming growth factor-beta superfamily (TGFβ, including BMP2, are effective in promoting chondrogenesis and osteogenesis in vivo in higher vertebrates, including humans. In the present study, we review the state of the art of this topic by a comparative analysis of skeletal tissue development, regeneration and renewal processes in tetrapods, and fin regeneration in fishes. A general conclusion of this study states that lepidotrichia is a special skeletal tissue different to cartilage, bone, enamel, or dentine in fishes, according to its extracellular matrix (ECM composition. However, the empirical analysis of inducing signals of skeletal tissues in fishes and tetrapods suggests that lepidotrichia is different to any responding features with main skeletal tissues. A number of new inductive molecules are arising from fin development and regeneration studies that might establish an empirical basis for further molecular approaches to mammal skeletal tissues differentiation. Despite the tissue dissimilarity, this empirical evidence might finally lead to clinical applications to skeletal disorders in humans.

  13. Mesenchymal stem cells (MSCs) as skeletal therapeutics - an update.

    Science.gov (United States)

    Saeed, Hamid; Ahsan, Muhammad; Saleem, Zikria; Iqtedar, Mehwish; Islam, Muhammad; Danish, Zeeshan; Khan, Asif Manzoor

    2016-01-01

    Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair/regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/serum or by loading onto repair/induction supportive resorb-able scaffolds. Thus, this review is aimed at highlighting a wide range of pertinent clinical therapeutic options of MSCs in the treatment of skeletal diseases and skeletal tissue regeneration. Additionally, in skeletal disease and regenerative sections, only the early and more recent preclinical evidences are discussed followed by all the pertinent clinical studies. Moreover, germane post transplant therapeutic mechanisms afforded by MSCs have also been conversed. Nonetheless, assertive use of MSCs in the clinic for skeletal disorders and repair is far from a mature therapeutic option, therefore, posed challenges and future directions are also discussed. Importantly, for uniformity at all instances, term MSCs is used throughout the review. PMID:27084089

  14. Peripheral endocannabinoids regulate skeletal muscle development and maintenance

    Directory of Open Access Journals (Sweden)

    Dongjiao Zhao

    2010-12-01

    Full Text Available As a principal tissue responsible for insulin-mediated glucose uptake, skeletal muscle is important for whole-body health. The role of peripheral endocannabinoids as regulators of skeletal muscle metabolism has recently gained a lot of interest, as endocannabinoid system disorders could cause peripheral insulin resistance. We investigated the role of the peripheral endocannabinoid system in skeletal muscle development and maintenance. Cultures of C2C12 cells, primary satellite cells and mouse skeletal muscle single fibers were used as model systems for our studies. We found an increase in cannabinoid receptor type 1 (CB1 mRNA and endocannabinoid synthetic enzyme mRNA skeletal muscle cells during differentiation. We also found that activation of CB1 inhibited myoblast differentiation, expanded the number of satellite cells, and stimulated the fast-muscle oxidative phenotype. Our findings contribute to understanding of the role of the endocannabinoid system in skeletal muscle metabolism and muscle oxygen consumption, and also help to explain the effects of the peripheral endocannabinoid system on whole-body energy balance.

  15. Type 2 diabetes mellitus and skeletal muscle metabolic function.

    Science.gov (United States)

    Phielix, Esther; Mensink, Marco

    2008-05-23

    Type 2 diabetic patients are characterized by a decreased fat oxidative capacity and high levels of circulating free fatty acids (FFAs). The latter is known to cause insulin resistance, in particularly in skeletal muscle, by reducing insulin stimulated glucose uptake, most likely via accumulation of lipid inside the muscle cell. A reduced skeletal muscle oxidative capacity can exaggerate this. Furthermore, type 2 diabetes is associated with impaired metabolic flexibility, i.e. an impaired switching from fatty acid to glucose oxidation in response to insulin. Thus, a reduced fat oxidative capacity and metabolic inflexibility are important components of skeletal muscle insulin resistance. The cause of these derangements in skeletal muscle of type 2 diabetic patients remains to be elucidated. An impaired mitochondrial function is a likely candidate. Evidence from both in vivo and ex vivo studies supports the idea that an impaired skeletal muscle mitochondrial function is related to the development of insulin resistance and type 2 diabetes mellitus. A decreased mitochondrial oxidative capacity in skeletal muscle was revealed in diabetic patients, using in vivo 31-Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). However, quantification of mitochondrial function using ex vivo high-resolution respirometry revealed opposite results. Future (human) studies should challenge this concept of impaired mitochondrial function underlying metabolic defects and prove if mitochondria are truly functional impaired in insulin resistance, or low in number, and whether it represents the primary starting point of pathogenesis of insulin resistance, or is just an other feature of the insulin resistant state. PMID:18342897

  16. Regulation of Skeletal Muscle by microRNAs.

    Science.gov (United States)

    Diniz, Gabriela Placoná; Wang, Da-Zhi

    2016-01-01

    MicroRNAs (miRNAs) are a class of small noncoding RNAs highly conserved across species. miRNAs regulate gene expression posttranscriptionally by base pairing to complementary sequences mainly in the 3'-untranslated region of their target mRNAs to induce mRNA cleavage and translational repression. Thousands of miRNAs have been identified in human and their function has been linked to the regulation of both physiological and pathological processes. The skeletal muscle is the largest human organ responsible for locomotion, posture, and body metabolism. Several conditions such as aging, immobilization, exercise, and diet are associated with alterations in skeletal muscle structure and function. The genetic and molecular pathways that regulate muscle development, function, and regeneration as well as muscular disease have been well established in past decades. In recent years, numerous studies have underlined the importance of miRNAs in the control of skeletal muscle development and function, through its effects on several biological pathways critical for skeletal muscle homeostasis. Furthermore, it has become clear that alteration of the expression of many miRNAs or genetic mutations of miRNA genes is associated with changes on myogenesis and on progression of several skeletal muscle diseases. The present review provides an overview of the current studies and recent progress in elucidating the complex role exerted by miRNAs on skeletal muscle physiology and pathology. © 2016 American Physiological Society. Compr Physiol 6:1279-1294, 2016. PMID:27347893

  17. An analysis of the alleged skeletal remains of Carin Göring.

    Science.gov (United States)

    Kjellström, Anna; Edlund, Hanna; Lembring, Maria; Ahlgren, Viktoria; Allen, Marie

    2012-01-01

    In 1991, treasure hunters found skeletal remains in an area close to the destroyed country residence of former Nazi leader Hermann Göring in northeastern Berlin. The remains, which were believed to belong to Carin Göring, who was buried at the site, were examined to determine whether it was possible to make a positive identification. The anthropological analysis showed that the remains come from an adult woman. The DNA analysis of several bone elements showed female sex, and a reference sample from Carin's son revealed mtDNA sequences identical to the remains. The profile has one nucleotide difference from the Cambridge reference sequence (rCRS), the common variant 263G. A database search resulted in a frequency of this mtDNA sequence of about 10% out of more than 7,000 European haplotypes. The mtDNA sequence found in the ulna, the cranium and the reference sample is, thus, very common among Europeans. Therefore, nuclear DNA analysis was attempted. The remains as well as a sample from Carin's son were successfully analysed for the three nuclear markers TH01, D7S820 and D8S1179. The nuclear DNA analysis of the two samples revealed one shared allele for each of the three markers, supporting a mother and son relationship. This genetic information together with anthropological and historical files provides an additional piece of circumstantial evidence in our efforts to identify the remains of Carin Göring.

  18. Apolipoprotein E alleles in Alzheimer`s and Parkinson`s patients

    Energy Technology Data Exchange (ETDEWEB)

    Poduslo, S.E. [Texas Tech Univ., Lubbock, TX (United States); Schwankhaus, J.D. [Department of Veterans Affairs, Lubbock, TX (United States)

    1994-09-01

    A number of investigators have found an association between the apolipoprotein E4 allele and Alzheimer`s disease. The E4 allele appears at a higher frequency in late onset familial Alzheimer`s patients. In our studies we obtained blood samples from early and late onset familial and sporadic Alzheimer`s patients and spouses, as well as from Parkinson`s patients. The patients were diagnosed as probable Alzheimer`s patients after a neurological examination, extensive blood work, and a CAT scan. The diagnosis was made according to the NINCDS-ADRDA criteria. The apolipoprotein E4 polymorphism was detected after PCR amplification of genomic DNA, restriction enzyme digestion with Hhal, and polyacrylamide gel electrophoresis. Ethidium bromide-stained bands at 91 bp were designated as allele 3, at 83 bp as allele 2, and at 72 bp as allele 4. Of the 84 probable Alzheimer`s patients (all of whom were Caucasian), 47 were heterozygous and 13 were homozygous for the E4 allele. There were 26 early onset patients; 13 were heterozygous and 7 homozygous for the E4 allele. The frequencies for the E4 allele for late onset familial patients was 0.45 and for sporadic patients was 0.37. We analyzed 77 spouses with an average age of 71.9 {plus_minus} 7.4 years as controls, and 15 were heterozygous for the E4 allele for an E4 frequency of 0.097. Of the 53 Parkinson`s patients, 11 had the E4 allele for a frequency of 0.113. Thus our findings support the association of the ApoE4 allele with Alzheimer`s disease.

  19. Major histocompatibility complex class I chain related (MIC) A gene, TNFa microsatellite alleles and TNFB alleles in juvenile idiopathic arthritis patients from Latvia.

    Science.gov (United States)

    Nikitina Zake, Liene; Cimdina, Ija; Rumba, Ingrida; Dabadghao, Preethi; Sanjeevi, Carani B

    2002-05-01

    In order to analyze involvement of major histocompatibility complex class I chain-related gene A (MICA) and tumor necrosis factor a (TNFa) microsatellite polymorphisms as well as TNFB gene in juvenile idiopathic arthritis (JIA), we studied 128 patients divided into groups according to clinical features [monoarthritis (n = 14), oligoarthritis (n = 58), polyarthritis (n = 50), and systemic (n = 6)], and 114 age- and sex-matched healthy controls from Latvia. DNA samples were amplified with specific primers and used for genotyping of MICA and TNFa microsatellite. Typing for a biallelic NcoI polymerase chain reaction RFLP polymorphism located at the first intron of TNFB gene was done as follows: restriction digests generated fragments of 555bp and 185bp for TNFB*1 allele, and 740bp for TNFB*2 allele. The results were compared between cases and controls. We found significant increase of MICA allele A4 (p = 0.009; odds ratio [OR] = 2.3) and allele TNFa2 (p = 0.0001; OR = 4.4) in patients compared with controls. The frequency of allele TNFa9 was significantly decreased (p = 0.0001; OR = 0.1) in patients with JIA. No significant differences of TNFB allele frequency were found. Our data suggest that MICA and TNFa microsatellite polymorphisms may be used as markers for determination of susceptibility and protection from JIA.

  20. Skeletal injuries associated with sexual abuse

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Karl; Chapman, Stephen [Department of Radiology, Birmingham Children' s Hospital, Steelhouse Lane, B4 6NH, Birmingham (United Kingdom); Hall, Christine M. [Department of Radiology, Great Ormond Street Hospital for Children, London (United Kingdom)

    2004-08-01

    Background: Sexual abuse is often associated with physical abuse, the most common injuries being bruising and other soft-tissue injuries, but fractures occur in 5% of sexually abused children. The fractures described to date have formed part of the spectrum of injuries in these children and have not been specifically related to the abusive act. Objective: To describe concurrent sexual abuse and fractures. Materials and methods: Three children with pelvic or femoral shaft injuries in association with sexual abuse. Results: A 3-year-old girl with extensive soft-tissue injuries to the arms, legs and perineum also sustained fractures of both pubic rami and the sacral side of the right sacro-iliac joint. A 5-month-old girl with an introital tear was shown to have an undisplaced left femoral shaft fracture. A 5-year-old girl presented with an acute abdomen and pneumoperitoneum due to a ruptured rectum following sexual abuse. She had old healed fractures of both pubic rami with disruption of the symphysis pubis. Conclusions: Although the finding of a perineal injury in a young child may be significant enough for the diagnosis of abuse, additional skeletal injuries revealed by radiography will assist in confirmation of that diagnosis and may be more common than hitherto suspected. (orig.)

  1. Ediacaran skeletal metazoan interpreted as a lophophorate.

    Science.gov (United States)

    Zhuravlev, A Yu; Wood, R A; Penny, A M

    2015-11-01

    While many skeletal biomineralized genera are described from Ediacaran (635-541 million years ago, Ma) strata, none have been suggested to have an affinity above the Porifera-Cnidaria metazoan grade. Here, we reinterpret the widespread terminal Ediacaran (approx. 550-541 Ma) sessile goblet-shaped Namacalathus as a triploblastic eumetazoan. Namacalathus has a stalked cup with radially symmetrical cross section, multiple lateral lumens and a central opening. We show that the skeleton of Namacalathus is composed of a calcareous foliated ultrastructure displaying regular concordant columnar inflections, with a possible inner organic-rich layer. These features point to an accretionary growth style of the skeleton and an affinity with the Lophotrochozoa, more specifically within the Lophophorata (Brachiopoda and Bryozoa). Additionally, we present evidence for asexual reproduction as expressed by regular budding in a bilateral pattern. The interpretation of Namacalathus as an Ediacaran total group lophophorate is consistent with an early radiation of the Lophophorata, as known early Cambrian representatives were sessile, mostly stalked forms, and in addition, the oldest known calcareous Brachiopoda (early Cambrian Obolellida) and Bryozoa (Ordovician Stenolaemata) possessed foliated ultrastructures. PMID:26538593

  2. Osteogenic sarcoma with skeletal muscle metastases

    Energy Technology Data Exchange (ETDEWEB)

    Peh, W.C.G. [Department of Diagnostic Radiology, The University of Hong Kong, Queen Mary Hospital (Hong Kong); Shek, T.W.H. [Department of Pathology, The University of Hong Kong, Queen Mary Hospital (Hong Kong); Wang Shihchang [Department of Diagnostic Imaging, National University of Singapore, National University Hospital (Singapore); Wong, J.W.K.; Chien, E.P. [Department of Orthopaedic Surgery, The University of Hong Kong, Queen Mary Hospital (Hong Kong)

    1999-05-01

    Two cases of osteogenic sarcoma with skeletal muscle metastases are described. A 40-year-old woman presented with progressive swelling of both calves and a soft tissue back lump. She had been diagnosed with mandibular chondroblastic osteogenic sarcoma 6 years earlier. Radiographs showed calcified masses. MRI scans and bone scintigraphy revealed multiple soft tissue masses in both calves. Bone scintigraphy also showed uptake in the back lump, right thigh and left lung base. Biopsy confirmed metastatic chondroblastic osteogenic sarcoma, which initially responded well to chemotherapy. However, the metastatic disease subsequently progressed rapidly and she died 21 months after presentation. The second case concerns a 20-year-old man who presented with a pathologic fracture of the humerus, which was found to be due to osteoblastic osteogenic sarcoma. He developed cerebral metastases 17 months later, followed by metastases at other sites. Calcified masses were subsequently seen on radiographs of the abdomen and chest. CT scans confirmed the presence of densely calcified muscle metastases in the abdominal wall, erector spinae and gluteal muscles. The patient`s disease progressed rapidly and he died 30 months after presentation. (orig.) With 6 figs., 29 refs.

  3. Highly extensible skeletal muscle in snakes.

    Science.gov (United States)

    Close, Matthew; Perni, Stefano; Franzini-Armstrong, Clara; Cundall, David

    2014-07-15

    Many snakes swallow large prey whole, and this process requires large displacements of the unfused tips of the mandibles and passive stretching of the soft tissues connecting them. Under these conditions, the intermandibular muscles are highly stretched but subsequently recover normal function. In the highly stretched condition we observed in snakes, sarcomere length (SL) increased 210% its resting value (SL0), and actin and myosin filaments no longer overlapped. Myofibrils fell out of register and triad alignment was disrupted. Following passive recovery, SLs returned to 82% SL0, creating a region of double-overlapping actin filaments. Recovery required recoil of intracellular titin filaments, elastic cytoskeletal components for realigning myofibrils, and muscle activation. Stretch of whole muscles exceeded that of sarcomeres as a result of extension of folded terminal tendon fibrils, stretching of extracellular elastin and independent slippage of muscle fibers. Snake intermandibular muscles thus provide a unique model of how basic components of vertebrate skeletal muscle can be modified to permit extreme extensibility.

  4. Body size prediction from juvenile skeletal remains.

    Science.gov (United States)

    Ruff, Christopher

    2007-05-01

    There are currently no methods for predicting body mass from juvenile skeletal remains and only a very limited number for predicting stature. In this study, stature and body mass prediction equations are generated for each year from 1 to 17 years of age using a subset of the Denver Growth Study sample, followed longitudinally (n = 20 individuals, 340 observations). Radiographic measurements of femoral distal metaphyseal and head breadth are used to predict body mass and long bone lengths are used to predict stature. In addition, pelvic bi-iliac breadth and long bone lengths are used to predict body mass in older adolescents. Relative prediction errors are equal to or smaller than those associated with similar adult estimation formulae. Body proportions change continuously throughout growth, necessitating age-specific formulae. Adult formulae overestimate stature and body mass in younger juveniles, but work well in 17-year-olds from the sample, indicating that in terms of body proportions they are representative of the general population. To illustrate use of the techniques, they are applied to the juvenile Homo erectus (ergaster) KNM-WT 15000 skeleton. New body mass and stature estimates for this specimen are similar to previous estimates derived using other methods. Body mass estimates range from 50 to 53 kg, and stature was probably slightly under 157 cm, although a precise stature estimate is difficult to determine due to differences in linear body proportions between KNM-WT 15000 and the Denver reference sample. PMID:17295297

  5. Satellite cell proliferation in adult skeletal muscle

    Science.gov (United States)

    Booth, Frank W. (Inventor); Thomason, Donald B. (Inventor); Morrison, Paul R. (Inventor); Stancel, George M. (Inventor)

    1995-01-01

    Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

  6. Skeletal injuries associated with sexual abuse

    International Nuclear Information System (INIS)

    Background: Sexual abuse is often associated with physical abuse, the most common injuries being bruising and other soft-tissue injuries, but fractures occur in 5% of sexually abused children. The fractures described to date have formed part of the spectrum of injuries in these children and have not been specifically related to the abusive act. Objective: To describe concurrent sexual abuse and fractures. Materials and methods: Three children with pelvic or femoral shaft injuries in association with sexual abuse. Results: A 3-year-old girl with extensive soft-tissue injuries to the arms, legs and perineum also sustained fractures of both pubic rami and the sacral side of the right sacro-iliac joint. A 5-month-old girl with an introital tear was shown to have an undisplaced left femoral shaft fracture. A 5-year-old girl presented with an acute abdomen and pneumoperitoneum due to a ruptured rectum following sexual abuse. She had old healed fractures of both pubic rami with disruption of the symphysis pubis. Conclusions: Although the finding of a perineal injury in a young child may be significant enough for the diagnosis of abuse, additional skeletal injuries revealed by radiography will assist in confirmation of that diagnosis and may be more common than hitherto suspected. (orig.)

  7. A Δ11 desaturase gene genealogy reveals two divergent allelic classes within the European corn borer (Ostrinia nubilalis

    Directory of Open Access Journals (Sweden)

    Harrison Richard G

    2010-04-01

    Full Text Available Abstract Background Moth pheromone mating systems have been characterized at the molecular level, allowing evolutionary biologists to study how changes in protein sequence or gene expression affect pheromone phenotype, patterns of mating, and ultimately, the formation of barriers to gene exchange. Recent studies of Ostrinia pheromones have focused on the diversity of sex pheromone desaturases and their role in the specificity of pheromone production. Here we produce a Δ11 desaturase genealogy within Ostrinia nubilalis. We ask what has been the history of this gene, and whether this history suggests that changes in Δ11 desaturase have been involved in the divergence of the E and Z O. nubilalis pheromone strains. Results The Δ11 desaturase gene genealogy does not differentiate O. nubilalis pheromone strains. However, we find two distinct clades, separated by 2.9% sequence divergence, that do not sort with pheromone strain, geographic origin, or emergence time. We demonstrate that these clades do not represent gene duplicates, but rather allelic variation at a single gene locus. Conclusions Analyses of patterns of variation at the Δ11 desaturase gene in ECB suggest that this enzyme does not contribute to reproductive isolation between pheromone strains (E and Z. However, our genealogy reveals two deeply divergent allelic classes. Standing variation at loci that contribute to mate choice phenotypes may permit novel pheromone mating systems to arise in the presence of strong stabilizing selection.

  8. Coordinated gene expression between skeletal muscle and intramuscular adipose tissue in growing beef cattle.

    Science.gov (United States)

    Roberts, S L; Lancaster, P A; DeSilva, U; Horn, G W; Krehbiel, C R

    2015-09-01

    Previous research indicates that metabolism and fiber type of skeletal muscle is related to intramuscular lipid content. It is hypothesized that changes in skeletal muscle gene expression influence adipose tissue development. The objective of this study was to determine differences in the metabolism and intercellular signaling of skeletal muscle fibers within the same muscle group that could be responsible for the initiation of intramuscular adipose tissue development and differentiation. Longissimus dorsi muscle samples were collected from steers ( = 12; 385 d of age; 378 kg BW) grazing wheat pasture. Longissimus muscle samples were dissected under magnification and sorted into 3 categories based on visual stage of adipose tissue development: immature intramuscular adipose tissue (MM), intermediate intramuscular adipose tissue (ME), and mature intramuscular adipose tissue (MA). Additionally, muscle fibers lying adjacent to each intramuscular adipose tissue (IM) category and those not associated with IM tissue were collected and stored separately. Quantitative real-time PCR was used to determine relative fold change in genes involved in metabolism, angiogenesis, formation of extracellular matrix, and intercellular signaling pathways in both LM and IM samples. Gene expression data were analyzed using a GLM that included the fixed effect of tissue. Pearson correlation coefficients were also computed between gene expression in LM and IM tissue samples that were at the same stage of development. and γ mRNA expression were 3.56- and 1.97-fold greater ( development categories. Genes associated with metabolism and angiogenesis in LM tissue showed no differences among stages of development. Myostatin expression did not change in LM tissue; however, expression of and mRNA decreased ( tissue had a strong positive correlation ( ≥ 0.69) with angiogenic growth factors in LM associated with MM IM; however, no correlation was observed in ME or MA IM. These data indicate a

  9. Salmonella Typhi shdA: pseudogene or allelic variant?

    Science.gov (United States)

    Urrutia, I M; Fuentes, J A; Valenzuela, L M; Ortega, A P; Hidalgo, A A; Mora, G C

    2014-08-01

    ShdA from Salmonella Typhimurium (ShdASTm) is a large outer membrane protein that specifically recognizes and binds to fibronectin. ShdASTm is involved in the colonization of the cecum and the Peyer's patches of terminal ileum in mice. On the other hand, shdA gene from Salmonella Typhi (shdASTy) has been considered a pseudogene (i.e. a nonfunctional sequence of genomic DNA) due to the presence of deletions and mutations that gave rise to premature stop codons. In this work we show that, despite the deletions and mutations, shdASTy is fully functional. S. Typhi ΔshdA mutants presented an impaired adherence and invasion of HEp-2 pre-treated with TGF-β1, an inducer of fibronectin production. Moreover, shdA from S. Typhi and S. Typhimurium seem to be equivalent since shdASTm restored the adherence and invasion of S. Typhi ΔshdA mutant to wild type levels. In addition, anti-FLAG mAbs interfered with the adherence and invasion of the S. Typhi shdA-3xFLAG strain. Finally, shdASTy encodes a detectable protein when heterologously expressed in Escherichia coli DH5α. The data presented here show that shdASTy is not a pseudogene, but a different functional allele compared with shdASTm. PMID:24859062

  10. Rotary drum separator system

    Science.gov (United States)

    Barone, Michael R. (Inventor); Murdoch, Karen (Inventor); Scull, Timothy D. (Inventor); Fort, James H. (Inventor)

    2009-01-01

    A rotary phase separator system generally includes a step-shaped rotary drum separator (RDS) and a motor assembly. The aspect ratio of the stepped drum minimizes power for both the accumulating and pumping functions. The accumulator section of the RDS has a relatively small diameter to minimize power losses within an axial length to define significant volume for accumulation. The pumping section of the RDS has a larger diameter to increase pumping head but has a shorter axial length to minimize power losses. The motor assembly drives the RDS at a low speed for separating and accumulating and a higher speed for pumping.

  11. On separable Pauli equations

    OpenAIRE

    Zhalij, Alexander

    2002-01-01

    We classify (1+3)-dimensional Pauli equations for a spin-1/2 particle interacting with the electro-magnetic field, that are solvable by the method of separation of variables. As a result, we obtain the eleven classes of vector-potentials of the electro-magnetic field A(t,x) providing separability of the corresponding Pauli equations. It is established, in particular, that the necessary condition for the Pauli equation to be separable into second-order matrix ordinary differential equations is...

  12. Microsatellite allele dose and configuration establishment (MADCE): an integrated approach for genetic studies in allopolyploids

    NARCIS (Netherlands)

    Dijk, van T.; Noordijk, Y.; Dubos, T.; Bink, M.C.A.M.; Visser, R.G.F.; Weg, van de W.E.

    2012-01-01

    BACKGROUND: Genetic studies in allopolyploid plants are challenging because of the presence of similar sub-genomes, which leads to multiple alleles and complex segregation ratios. In this study, we describe a novel method for establishing the exact dose and configuration of microsatellite alleles fo

  13. An Updated Collection of Sequence Barcoded Temperature-Sensitive Alleles of Yeast Essential Genes.

    Science.gov (United States)

    Kofoed, Megan; Milbury, Karissa L; Chiang, Jennifer H; Sinha, Sunita; Ben-Aroya, Shay; Giaever, Guri; Nislow, Corey; Hieter, Philip; Stirling, Peter C

    2015-09-01

    Systematic analyses of essential gene function using mutant collections in Saccharomyces cerevisiae have been conducted using collections of heterozygous diploids, promoter shut-off alleles, through alleles with destabilized mRNA, destabilized protein, or bearing mutations that lead to a temperature-sensitive (ts) phenotype. We previously described a method for construction of barcoded ts alleles in a systematic fashion. Here we report the completion of this collection of alleles covering 600 essential yeast genes. This resource covers a larger gene repertoire than previous collections and provides a complementary set of strains suitable for single gene and genomic analyses. We use deep sequencing to characterize the amino acid changes leading to the ts phenotype in half of the alleles. We also use high-throughput approaches to describe the relative ts behavior of the alleles. Finally, we demonstrate the experimental usefulness of the collection in a high-content, functional genomic screen for ts alleles that increase spontaneous P-body formation. By increasing the number of alleles and improving the annotation, this ts collection will serve as a community resource for probing new aspects of biology for essential yeast genes. PMID:26175450

  14. Revealing the Genetic Variation and Allele Heterozygote Javanese and Arab Families in Malang East Java Indonesia

    Directory of Open Access Journals (Sweden)

    Nila Kartika Sari

    2014-02-01

    Results: Our result showed that the genetic variability and heterozygote allele increasing by using the 13 CODIS markers from the first generation to the next generation with paternity testing from each family were matched. Conclusion: We can conclude that in a Javanese-Arab family ethnic seems stimulate the increasing genetic variation and allele heterozygote.

  15. Identification of novel alleles of the rice blast resistance gene Pi54

    Science.gov (United States)

    Vasudevan, Kumar; Gruissem, Wilhelm; Bhullar, Navreet K.

    2015-10-01

    Rice blast is one of the most devastating rice diseases and continuous resistance breeding is required to control the disease. The rice blast resistance gene Pi54 initially identified in an Indian cultivar confers broad-spectrum resistance in India. We explored the allelic diversity of the Pi54 gene among 885 Indian rice genotypes that were found resistant in our screening against field mixture of naturally existing M. oryzae strains as well as against five unique strains. These genotypes are also annotated as rice blast resistant in the International Rice Genebank database. Sequence-based allele mining was used to amplify and clone the Pi54 allelic variants. Nine new alleles of Pi54 were identified based on the nucleotide sequence comparison to the Pi54 reference sequence as well as to already known Pi54 alleles. DNA sequence analysis of the newly identified Pi54 alleles revealed several single polymorphic sites, three double deletions and an eight base pair deletion. A SNP-rich region was found between a tyrosine kinase phosphorylation site and the nucleotide binding site (NBS) domain. Together, the newly identified Pi54 alleles expand the allelic series and are candidates for rice blast resistance breeding programs.

  16. Correlation in chicken between the marker LEI0258 alleles and Major Histocompatibility Complex sequences

    DEFF Research Database (Denmark)

    Chazara, Olympe; Juul-Madsen, Helle Risdahl; Chang, Chi-Seng;

    Background The LEI0258 marker is located within the B region of the chicken Major Histocompatibility Complex (MHC), and is surprisingly well associated with serology. Therefore, the correlation between the LEI0258 alleles and the MHC class I and the class II alleles at the level of sequences is w...

  17. Overdispersion in allelic counts and θ-correction in forensic genetics

    DEFF Research Database (Denmark)

    Tvedebrink, Torben

    2010-01-01

    We present a statistical model for incorporating the extra variability in allelic counts due to subpopulation structures. In forensic genetics, this effect is modelled by the identical-by-descent parameter θ, which measures the relationship between pairs of alleles within a population relative...

  18. HLA-DRB1 allele polymorphisms in genetic susceptibility to esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun Lin; Chang-Sheng Deng; Jie Sun; Xian-Gong Zheng; Xing Huang; Yan Zhou; Ping Xiong; Ya-Ping Wang

    2003-01-01

    AIM: To probe into the genetic susceptibility of HLA-DRB1 alleles to esophageal carcinoma in Han Chinese in Hubei Province.METHODS: HLA-DRB1 allele polymorphisms were typed by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 42 unrelated patients with esophageal cancer and 136 unrelated normal control subjects and the associated HLA-DRB1 allele was measured by nucleotide sequence analysis with PCR.SAS software was used in statistics.RESULTS: Allele frequency (AF) of HLA-DRB1·0901 was significantly higher in esophageal carcinoma patients than that in the normal controls (0.2500 vs0.1397, P=0.028, the odds ratio 2.053, etiologic fraction 0.1282). After analyzed the allele nucleotide sequence of HLA-DRB1·0901 which approachs to the corresponded exon 2 sequence of the allele in genebank. There was no association between patients and controls in the rested HLA-DRB1 alleles.CONCLUSION: HLA-DRB1·0901 allele is more common in the patients with esophageal carcinoma than in the healthy controls, which is positively associated with the patients of Hubei Han Chinese. Individuals carrying HLA-DRB1·0901may be susceptible to esophageal carcinoma.

  19. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Øhlenschlaeger, Tommy; Garred, Peter; Madsen, Hans O;

    2004-01-01

    Cardiovascular disease is an important complication in patients with systemic lupus erythematosus (SLE). Variant alleles of the mannose-binding lectin gene are associated with SLE as well as with severe atherosclerosis. We determined whether mannose-binding lectin variant alleles were associated...

  20. Evidence for multiple alleles effecting muscling and fatness at the Ovine GDF8 locus

    Directory of Open Access Journals (Sweden)

    Oddy V Hutton

    2007-11-01

    Full Text Available Abstract Background The current investigation surveyed genetic polymorphism at the ovine GDF8 locus and determined its contribution to variation in muscling and fatness in sheep. Results Re-sequencing 2988 bp from a panel of 15 sires revealed a total of six SNP, none of which were located within exons of the gene. One of the identified SNP, g+6723G>A, is known to increase muscularity within the Belgian Texel. A genetic survey of 326 animals revealed that the mutation is near fixation within Australian Texels and present in additional breeds including White Suffolk, Poll Dorset and Lincoln. Using a resource population comprising 15 sires and 1191 half-sib progeny with genotypic data, the effect of this and other SNP was tested against a set of 50 traits describing growth, muscling, fatness, yield, meat and eating quality. The loss of function allele (g+6723A showed significant effects on slaughter measurements of muscling and fatness. No effect was detected on objectively assessed meat quality however evidence was found for an association between g+6723G>A, decreased intramuscular fat and reduced eating quality. Haplotype analysis using flanking microsatellites was performed to search for evidence of currently unidentified mutations which might affect production traits. Four haplotypes were identified that do not carry g+6723A but which showed significant associations with muscling and fatness. Conclusion The finding that g+6723G>A is present within Australian sheep facilitated an independent evaluation into its phenotypic consequence. Testing was conducted using a separate genetic background and animals raised in different environments to the Belgian Texel in which it was first identified. The observation that the direction and size of effects for g+6723A is approximately consistent represented a robust validation of the effects of the mutation. Based on observed allele frequencies within breeds, selection for g+6723A will have the largest

  1. The number of self-incompatibility alleles in a finite, subdivided population

    DEFF Research Database (Denmark)

    Schierup, M H

    1998-01-01

    The actual and effective number of gametophytic self-incompatibility alleles maintained at mutation-drift-selection equilibrium in a finite population subdivided as in the island model is investigated by stochastic simulations. The existing theory founded by Wright predicts that for a given...... population size the number of alleles maintained increases monotonically with decreasing migration as is the case for neutral alleles. The simulation results here show that this is not true. At migration rates above Nm = 0.01-0.1, the actual and effective number of alleles is lower than for an undivided...... population with the same number of individuals, and, contrary to Wright's theoretical expectation, the number of alleles is not much higher than for an undivided population unless Nm

  2. Low-dose biplanar skeletal survey versus digital skeletal survey in multiple myeloma

    International Nuclear Information System (INIS)

    To evaluate the low-dose biplanar (LDB) skeletal survey (SS) for the assessment of focal bone involvement in patients with multiple myeloma (MM) as compared with digital SS and to compare the two techniques in terms of image quality, patient comfort and radiation exposure. Fifty-six consecutive patients with newly diagnosed or first relapsed MM underwent LDB and digital SS on the same day. These were assessed by two radiologists for the detection of focal bone lesions. In the case of discordance, whole-body MR imaging was performed. Image quality, patient comfort and radiation dose were also assessed. Fifty-six patients (M:30, F:26, mean age, 62 years) with newly diagnosed (n = 21) or first relapse MM (n = 35) were enrolled. A total of 473 bone lesions in 46 patients (82 %) were detected. Out of that total, digital SS detected significantly more lesions than LDB SS (451 [95.35 %] versus 467 [98.73 %]), especially in osteopenic and obese patients. Overall patient satisfaction was greater with LDB SS (48.6 %) compared with digital SS (2.7 %). The radiation dose was significantly reduced (by a factor of 7.8) with the LDB X-ray device. Low-dose biplanar skeletal surveys cannot replace digital SS in all patients suffering from multiple myeloma. (orig.)

  3. Low-dose biplanar skeletal survey versus digital skeletal survey in multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Boutry, Nathalie [University Hospital of Jeanne de Flandre and University of Lille 2, Departments of Pediatric and Musculoskeletal Imaging, Lille (France); University Hospital of Jeanne de Flandre and University of Lille 2, Department of Pediatric Imaging, Lille (France); Hopital Jeanne de Flandre, Service de Radiopediatrie, Lille (France); Dutouquet, Bastien; Cotten, Anne [University Hospital of Roger Salengro and University of Lille 2, Department of Musculoskeletal Imaging, Lille (France); Leleu, Xavier [University Hospital of Claude Huriez and University of Lille 2, Clinical Hematology Department, Lille (France); Vieillard, Marie-Helene [University Hospital of Roger Salengro and University of Lille 2, Rheumatology Department, Lille (France); Duhamel, Alain [University of Lille 2, Department of Medical Statistics, Lille (France)

    2013-08-15

    To evaluate the low-dose biplanar (LDB) skeletal survey (SS) for the assessment of focal bone involvement in patients with multiple myeloma (MM) as compared with digital SS and to compare the two techniques in terms of image quality, patient comfort and radiation exposure. Fifty-six consecutive patients with newly diagnosed or first relapsed MM underwent LDB and digital SS on the same day. These were assessed by two radiologists for the detection of focal bone lesions. In the case of discordance, whole-body MR imaging was performed. Image quality, patient comfort and radiation dose were also assessed. Fifty-six patients (M:30, F:26, mean age, 62 years) with newly diagnosed (n = 21) or first relapse MM (n = 35) were enrolled. A total of 473 bone lesions in 46 patients (82 %) were detected. Out of that total, digital SS detected significantly more lesions than LDB SS (451 [95.35 %] versus 467 [98.73 %]), especially in osteopenic and obese patients. Overall patient satisfaction was greater with LDB SS (48.6 %) compared with digital SS (2.7 %). The radiation dose was significantly reduced (by a factor of 7.8) with the LDB X-ray device. Low-dose biplanar skeletal surveys cannot replace digital SS in all patients suffering from multiple myeloma. (orig.)

  4. Laser-Beam Separator

    Science.gov (United States)

    Mcdermid, I. S.

    1984-01-01

    Train of prisms and optical stop separate fundamental beam of laser from second and higher order harmonics of beam produced in certain crystals and by stimulated Raman scattering in gases and liquids.

  5. Molten salt electrolyte separator

    Science.gov (United States)

    Kaun, Thomas D.

    1996-01-01

    A molten salt electrolyte/separator for battery and related electrochemical systems including a molten electrolyte composition and an electrically insulating solid salt dispersed therein, to provide improved performance at higher current densities and alternate designs through ease of fabrication.

  6. Separator for alkaline batteries

    Science.gov (United States)

    Hoyt, H. W.; Pfluger, H. L.

    1968-01-01

    Separator compositions have been tested as components of three-plate silver-zinc oxide cells in a standard cycling test. Six materials meet imposed requirements, giving cycling performance superior to cellophane.

  7. The microcephalin ancestral allele in a Neanderthal individual

    DEFF Research Database (Denmark)

    Lari, Martina; Rizzi, Ermanno; Milani, Lucio;

    2010-01-01

    The high frequency (around 0.70 worldwide) and the relatively young age (between 14,000 and 62,000 years) of a derived group of haplotypes, haplogroup D, at the microcephalin (MCPH1) locus led to the proposal that haplogroup D originated in a human lineage that separated from modern humans >1...

  8. Distal humeral epiphyseal separation.

    Science.gov (United States)

    Moucha, Calin S; Mason, Dan E

    2003-10-01

    Distal humeral epiphyseal separation is an uncommon injury that is often misdiagnosed upon initial presentation. To make a timely, correct diagnosis, the treating physician must have a thorough understanding of basic anatomical relationships and an awareness of the existence of this injury. This is a case of a child who sustained a separation of the distal humeral epiphysis, as well as multiple other bony injuries, secondary to child abuse.

  9. Chiral separation in microflows

    OpenAIRE

    Kostur, Marcin; Schindler, Michael; Talkner, Peter; Hänggi, Peter

    2005-01-01

    Molecules that only differ by their chirality, so called enantiomers, often possess different properties with respect to their biological function. Therefore, the separation of enantiomers presents a prominent challenge in molecular biology and belongs to the ``Holy Grail'' of organic chemistry. We suggest a new separation technique for chiral molecules that is based on the transport properties in a microfluidic flow with spatially variable vorticity. Because of their size the thermal fluctua...

  10. Hydrogen separation process

    Science.gov (United States)

    Mundschau, Michael; Xie, Xiaobing; Evenson, IV, Carl; Grimmer, Paul; Wright, Harold

    2011-05-24

    A method for separating a hydrogen-rich product stream from a feed stream comprising hydrogen and at least one carbon-containing gas, comprising feeding the feed stream, at an inlet pressure greater than atmospheric pressure and a temperature greater than 200.degree. C., to a hydrogen separation membrane system comprising a membrane that is selectively permeable to hydrogen, and producing a hydrogen-rich permeate product stream on the permeate side of the membrane and a carbon dioxide-rich product raffinate stream on the raffinate side of the membrane. A method for separating a hydrogen-rich product stream from a feed stream comprising hydrogen and at least one carbon-containing gas, comprising feeding the feed stream, at an inlet pressure greater than atmospheric pressure and a temperature greater than 200.degree. C., to an integrated water gas shift/hydrogen separation membrane system wherein the hydrogen separation membrane system comprises a membrane that is selectively permeable to hydrogen, and producing a hydrogen-rich permeate product stream on the permeate side of the membrane and a carbon dioxide-rich product raffinate stream on the raffinate side of the membrane. A method for pretreating a membrane, comprising: heating the membrane to a desired operating temperature and desired feed pressure in a flow of inert gas for a sufficient time to cause the membrane to mechanically deform; decreasing the feed pressure to approximately ambient pressure; and optionally, flowing an oxidizing agent across the membrane before, during, or after deformation of the membrane. A method of supporting a hydrogen separation membrane system comprising selecting a hydrogen separation membrane system comprising one or more catalyst outer layers deposited on a hydrogen transport membrane layer and sealing the hydrogen separation membrane system to a porous support.

  11. Circadian rhythms, the molecular clock, and skeletal muscle.

    Science.gov (United States)

    Lefta, Mellani; Wolff, Gretchen; Esser, Karyn A

    2011-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock mechanism found in most, if not all, cell types including skeletal muscle. The mammalian molecular clock is a complex of multiple oscillating networks that are regulated through transcriptional mechanisms, timed protein turnover, and input from small molecules. At this time, very little is known about circadian aspects of skeletal muscle function/metabolism but some progress has been made on understanding the molecular clock in skeletal muscle. The goal of this chapter is to provide the basic terminology and concepts of circadian rhythms with a more detailed review of the current state of knowledge of the molecular clock, with reference to what is known in skeletal muscle. Research has demonstrated that the molecular clock is active in skeletal muscles and that the muscle-specific transcription factor, MyoD, is a direct target of the molecular clock. Skeletal muscle of clock-compromised mice, Bmal1(-/-) and Clock(Δ19) mice, are weak and exhibit significant disruptions in expression of many genes required for adult muscle structure and metabolism. We suggest that the interaction between the molecular clock, MyoD, and metabolic factors, such as PGC-1, provide a potential system of feedback loops that may be critical for both maintenance and adaptation of skeletal muscle.

  12. The functional importance of sequence versus expression variability of MHC alleles in parasite resistance.

    Science.gov (United States)

    Axtner, Jan; Sommer, Simone

    2012-12-01

    Understanding selection processes driving the pronounced allelic polymorphism of the major histocompatibility complex (MHC) genes and its functional associations to parasite load have been the focus of many recent wildlife studies. Two main selection scenarios are currently debated which explain the susceptibility or resistance to parasite infections either by the effects of (1) specific MHC alleles which are selected frequency-dependent in space and time or (2) a heterozygote or divergent allele advantage. So far, most studies have focused only on structural variance in co-evolutionary processes although this might not be the only trait subject to natural selection. In the present study, we analysed structural variance stretching from exon1 through exon3 of MHC class II DRB genes as well as genotypic expression variance in relation to the gastrointestinal helminth prevalence and infection intensity in wild yellow-necked mice (Apodemus flavicollis). We found support for the functional importance of specific alleles both on the sequence and expression level. By resampling a previously investigated study population we identified specific MHC alleles affected by temporal shifts in parasite pressure and recorded associated changes in allele frequencies. The allele Apfl-DRB*23 was associated with resistance to infections by the oxyurid nematode Syphacia stroma and at the same time with susceptibility to cestode infection intensity. In line with our expectation, MHC mRNA transcript levels tended to be higher in cestode-infected animals carrying the allele Apfl-DRB*23. However, no support for a heterozygote or divergent allele advantage on the sequence or expression level was detected. The individual amino acid distance of genotypes did not explain individual differences in parasite loads and the genetic distance had no effect on MHC genotype expression. For ongoing studies on the functional importance of expression variance in parasite resistance, allele

  13. On separable Pauli equations

    International Nuclear Information System (INIS)

    We classify (1+3)-dimensional Pauli equations for a spin-(1/2) particle interacting with the electro-magnetic field, that are solvable by the method of separation of variables. As a result, we obtain the 11 classes of vector-potentials of the electro-magnetic field A(t,x(vector sign))=(A0(t,x(vector sign)), A(vector sign)(t,x(vector sign))) providing separability of the corresponding Pauli equations. It is established, in particular, that the necessary condition for the Pauli equation to be separable into second-order matrix ordinary differential equations is its equivalence to the system of two uncoupled Schroedinger equations. In addition, the magnetic field has to be independent of spatial variables. We prove that coordinate systems and the vector-potentials of the electro-magnetic field providing the separability of the corresponding Pauli equations coincide with those for the Schroedinger equations. Furthermore, an efficient algorithm for constructing all coordinate systems providing the separability of Pauli equation with a fixed vector-potential of the electro-magnetic field is developed. Finally, we describe all vector-potentials A(t,x(vector sign)) that (a) provide the separability of Pauli equation, (b) satisfy vacuum Maxwell equations without currents, and (c) describe non-zero magnetic field

  14. A Novel Real-time Fluorescence Mutant-allele-specific Amplification Method for Rapid Single Nucleotide Polymorphism Analysis

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Current methods for single nucleotide polymorphism (SNP) analysis are timeconsuming and complicated. We aimed at development of one-step real-time fluorescence mutant-allele-specific amplification (MASA) method for rapid SNP analysis. The method is a marriage of two technologies: MASA primers for target DNA and a double-stranded DNA-selective fluorescent dye, SYBR Green I. Genotypes are separated according to the different threshold cycles of the wild-type and mutant primers. K-ras oncogene was used as a target to validate the feasibility of the method. The experimental results showed that the different genotypes can be clearly discriminated by the assay. The real-time fluorescence MASA method will have an enormous potential for fast and reliable SNP analysis due to its simplicity and low cost.

  15. The Physical Model of Magnetic Separation in a Plate Separator

    OpenAIRE

    Brożek, M.

    1999-01-01

    The results of magnetic separation depend on many factors, such as physical properties of particles of the separated mixture, magnetic intensity, particle sizes, separation conditions (constant or alternating field, dry or wet separation) and others. The formulae representing the dependence of separation results on the above mentioned factors are obtained from the model. The mathematical model presents only some general dependences of separations results on time or length of the separation pa...

  16. Computer simulation of free settling and skeletal settling during liquid phase sintering

    Directory of Open Access Journals (Sweden)

    Nikolić Z.S.

    2006-01-01

    Full Text Available In recent years, a range of computer simulation models leading to a better understanding of liquid phase sintering phenomena, have been developed with the aim of simulating the detailed evolution of microstructure during grain growth. Some liquid phase sintered materials show both macrostructural and microstructural effects associated with gravity force. Therefore we will develop a numerical procedure for the estimation of how much gravity will influence domain (two-dimensional particle representation growth, domain boundary migration and solid skeleton formation due to gravity induced segregation during liquid phase sintering. The method used for the simulation of a gravity field will be based on the settling procedure. Gravity induced settling will be separated into two stages - Free Settling and Skeletal Settling. Isolated solid phase domains fall under gravity and slide down over the already settled domains (free settling. During settling they make point contacts with each other. Necks between them then form and start to grow until the equilibrium dihedral angle between the domain boundaries and the liquid is established. Thus a solid skeleton forms and skeletal settling of a connected solid structure takes place. .

  17. Oral conjugated linoleic acid supplementation enhanced glycogen resynthesis in exercised human skeletal muscle.

    Science.gov (United States)

    Tsao, Jung-Piao; Liao, Su-Fen; Korivi, Mallikarjuna; Hou, Chien-Wen; Kuo, Chia-Hua; Wang, Hsueh-Fang; Cheng, I-Shiung

    2015-01-01

    Present study examined the effects of conjugated linoleic acid (CLA) supplementation on glycogen resynthesis in exercised human skeletal muscle. Twelve male participants completed a cross-over trial with CLA (3.8 g/day for 8 week) or placebo supplements by separation of 8 weeks. CLA is a mixture of trans-10 cis-12 and cis-9 trans-11 isomers (50:50). On experiment day, all participants performed 60-min cycling exercise at 75% VO2 max, then consumed a carbohydrate meal immediately after exercise and recovered for 3 h. Biopsied muscle samples from vastus lateralis were obtained immediately (0 h) and 3 h following exercise. Simultaneously, blood and gaseous samples were collected for every 30 min during 3-h recovery. Results showed significantly increased muscle glycogen content with CLA after a single bout of exercise (P Gaseous exchange data showed no beneficial effect of CLA on fat oxidation, instead lower non-esterified fatty acid and glycerol levels were found at 0 h. Our findings conclude that CLA supplementation can enhance the glycogen resynthesis rate in exercised human skeletal muscle. PMID:25385360

  18. Effect of vitamin D on skeletal muscle.

    Science.gov (United States)

    Walrand, Stéphane

    2016-06-01

    Beyond its traditional biological roles on bone health, extra-skeletal effects of vitamin D are currently under extensive research. The expression of the vitamin D receptor in most tissues has also strengthened the argument for its multiple functions. Among these, the effect of vitamin D on the mass and muscle performance has long been discussed. In ancient Greece, Herodotus recommended the sun as a cure for the "weak and soft muscles" and former Olympians exposed to sunlight to improve their physical performance. In 1952, Dr Spellerberg, a sports physiologist, has conducted an extensive study on the effects of UV irradiation on the performance of elite athletes. Following the significant results of this investigation, the scientist has informed the Olympic Committee that UV irradiation had a "persuasive" effect on physical performance and motor skills. These data are consistent with many subsequent studies reporting an improvement in physical activity, speed and endurance in young subjects treated with UV or with supplements containing vitamin D. Additional observation indicates a significant effect on muscle strength, particularly in the lower limbs. Concerning the mechanisms involved, some recent fundamental studies have shown that vitamin D exerts some molecular effects within the muscle cell. Specifically, a regulatory effect of vitamin D on calcium flux, mineral homeostasis and signaling pathways controlling protein anabolism has been reported in muscle tissue. Several epidemiological studies show that low vitamin D status is always associated with a decrease in muscle mass, strength and contractile capacity in older people. Vitamin D deficiency accelerates muscle loss with age (sarcopenia), and therefore leads to a reduction in physical capacity and to an increased risk of falls and fractures. In contrast, an additional intake of vitamin D in older people significantly improves muscle function and physical performance. PMID:27100224

  19. The Dmp1-SOST Transgene Interacts With and Downregulates the Dmp1-Cre Transgene and the Rosa(Notch) Allele.

    Science.gov (United States)

    Zanotti, Stefano; Canalis, Ernesto

    2016-05-01

    Activation of Notch1 in osteocytes of Rosa(Notch) mice, where a loxP-flanked STOP cassette and the Nicd coding sequence were targeted to the reverse orientation splice acceptor (Rosa)26 locus, causes osteopetrosis associated with suppressed Sost expression and enhanced Wnt signaling. To determine whether Sost downregulation mediates the effects of Notch activation in osteocytes, Rosa(Notch) mice were crossed with transgenics expressing Cre recombinase or SOST under the control of the dentin matrix protein (Dmp)1 promoter. Dmp1-SOST transgenics displayed vertebral osteopenia and a modest femoral cancellous and cortical bone phenotype, whereas hemizygous Dmp1-Cre transgenics heterozygous for the Rosa(Notch) allele (Dmp1-Cre;Rosa(Notch)) exhibited osteopetrosis. The phenotype of Notch activation in osteocytes was prevented in Dmp1-Cre;Rosa(Notch) mice hemizygous for the Dmp1-SOST transgene. The effect was associated with downregulated Notch signaling and suppressed Dmp1 and Rosa26 expression. To test whether SOST regulates Notch expression in osteocytes, cortical bone cultures from Dmp1-Cre;Rosa(Notch) mice or from Rosa(Notch) control littermates were exposed to recombinant human SOST. The addition of SOST had only modest effects on Notch target gene mRNA levels and suppressed Dmp1, but not Cre or Rosa26, expression. These findings suggest that prevention of the Dmp1-Cre;Rosa(Notch) skeletal phenotype by Dmp1-SOST is not secondary to SOST expression but to interactions among the Dmp1-SOST and Dmp1-Cre transgenes and the Rosa26 locus. In conclusion, the Dmp1-SOST transgene suppresses the expression of the Dmp1-Cre transgene and of Rosa26. PMID:26456319

  20. Demographic history and rare allele sharing among human populations

    Science.gov (United States)

    Gravel, Simon; Henn, Brenna M.; Gutenkunst, Ryan N.; Indap, Amit R.; Marth, Gabor T.; Clark, Andrew G.; Yu, Fuli; Gibbs, Richard A.; Bustamante, Carlos D.; Altshuler, David L.; Durbin, Richard M.; Abecasis, Gonçalo R.; Bentley, David R.; Chakravarti, Aravinda; Clark, Andrew G.; Collins, Francis S.; De La Vega, Francisco M.; Donnelly, Peter; Egholm, Michael; Flicek, Paul; Gabriel, Stacey B.; Gibbs, Richard A.; Knoppers, Bartha M.; Lander, Eric S.; Lehrach, Hans; Mardis, Elaine R.; McVean, Gil A.; Nickerson, Debbie A.; Peltonen, Leena; Schafer, Alan J.; Sherry, Stephen T.; Wang, Jun; Wilson, Richard K.; Gibbs, Richard A.; Deiros, David; Metzker, Mike; Muzny, Donna; Reid, Jeff; Wheeler, David; Wang, Jun; Li, Jingxiang; Jian, Min; Li, Guoqing; Li, Ruiqiang; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Jian; Wang, Wei; Yang, Huanming; Zhang, Xiuqing; Zheng, Huisong; Lander, Eric S.; Altshuler, David L.; Ambrogio, Lauren; Bloom, Toby; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Jaffe, David B.; Shefler, Erica; Sougnez, Carrie L.; Bentley, David R.; Gormley, Niall; Humphray, Sean; Kingsbury, Zoya; Koko-Gonzales, Paula; Stone, Jennifer; McKernan, Kevin J.; Costa, Gina L.; Ichikawa, Jeffry K.; Lee, Clarence C.; Sudbrak, Ralf; Lehrach, Hans; Borodina, Tatiana A.; Dahl, Andreas; Davydov, Alexey N.; Marquardt, Peter; Mertes, Florian; Nietfeld, Wilfiried; Rosenstiel, Philip; Schreiber, Stefan; Soldatov, Aleksey V.; Timmermann, Bernd; Tolzmann, Marius; Egholm, Michael; Affourtit, Jason; Ashworth, Dana; Attiya, Said; Bachorski, Melissa; Buglione, Eli; Burke, Adam; Caprio, Amanda; Celone, Christopher; Clark, Shauna; Conners, David; Desany, Brian; Gu, Lisa; Guccione, Lorri; Kao, Kalvin; Kebbel, Andrew; Knowlton, Jennifer; Labrecque, Matthew; McDade, Louise; Mealmaker, Craig; Minderman, Melissa; Nawrocki, Anne; Niazi, Faheem; Pareja, Kristen; Ramenani, Ravi; Riches, David; Song, Wanmin; Turcotte, Cynthia; Wang, Shally; Mardis, Elaine R.; Wilson, Richard K.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Weinstock, George; Durbin, Richard M.; Burton, John; Carter, David M.; Churcher, Carol; Coffey, Alison; Cox, Anthony; Palotie, Aarno; Quail, Michael; Skelly, Tom; Stalker, James; Swerdlow, Harold P.; Turner, Daniel; De Witte, Anniek; Giles, Shane; Gibbs, Richard A.; Wheeler, David; Bainbridge, Matthew; Challis, Danny; Sabo, Aniko; Yu, Fuli; Yu, Jin; Wang, Jun; Fang, Xiaodong; Guo, Xiaosen; Li, Ruiqiang; Li, Yingrui; Luo, Ruibang; Tai, Shuaishuai; Wu, Honglong; Zheng, Hancheng; Zheng, Xiaole; Zhou, Yan; Li, Guoqing; Wang, Jian; Yang, Huanming; Marth, Gabor T.; Garrison, Erik P.; Huang, Weichun; Indap, Amit; Kural, Deniz; Lee, Wan-Ping; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; Daly, Mark J.; DePristo, Mark A.; Altshuler, David L.; Ball, Aaron D.; Banks, Eric; Bloom, Toby; Browning, Brian L.; Cibulskis, Kristian; Fennell, Tim J.; Garimella, Kiran V.; Grossman, Sharon R.; Handsaker, Robert E.; Hanna, Matt; Hartl, Chris; Jaffe, David B.; Kernytsky, Andrew M.; Korn, Joshua M.; Li, Heng; Maguire, Jared R.; McCarroll, Steven A.; McKenna, Aaron; Nemesh, James C.; Philippakis, Anthony A.; Poplin, Ryan E.; Price, Alkes; Rivas, Manuel A.; Sabeti, Pardis C.; Schaffner, Stephen F.; Shefler, Erica; Shlyakhter, Ilya A.; Cooper, David N.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Stenson, Peter D.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Bustamante, Carlos D.; Clark, Andrew G.; Boyko, Adam; Degenhardt, Jeremiah; Gravel, Simon; Gutenkunst, Ryan N.; Kaganovich, Mark; Keinan, Alon; Lacroute, Phil; Ma, Xin; Reynolds, Andy; Clarke, Laura; Flicek, Paul; Cunningham, Fiona; Herrero, Javier; Keenen, Stephen; Kulesha, Eugene; Leinonen, Rasko; McLaren, William M.; Radhakrishnan, Rajesh; Smith, Richard E.; Zalunin, Vadim; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Stütz, Adrian M.; Humphray, Sean; Bauer, Markus; Cheetham, R. Keira; Cox, Tony; Eberle, Michael; James, Terena; Kahn, Scott; Murray, Lisa; Chakravarti, Aravinda; Ye, Kai; De La Vega, Francisco M.; Fu, Yutao; Hyland, Fiona C. L.; Manning, Jonathan M.; McLaughlin, Stephen F.; Peckham, Heather E.; Sakarya, Onur; Sun, Yongming A.; Tsung, Eric F.; Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.; Sudbrak, Ralf; Albrecht, Marcus W.; Amstislavskiy, Vyacheslav S.; Herwig, Ralf; Parkhomchuk, Dimitri V.; Sherry, Stephen T.; Agarwala, Richa; Khouri, Hoda M.; Morgulis, Aleksandr O.; Paschall, Justin E.; Phan, Lon D.; Rotmistrovsky, Kirill E.; Sanders, Robert D.; Shumway, Martin F.; Xiao, Chunlin; McVean, Gil A.; Auton, Adam; Iqbal, Zamin; Lunter, Gerton; Marchini, Jonathan L.; Moutsianas, Loukas; Myers, Simon; Tumian, Afidalina; Desany, Brian; Knight, James; Winer, Roger; Craig, David W.; Beckstrom-Sternberg, Steve M.; Christoforides, Alexis; Kurdoglu, Ahmet A.; Pearson, John V.; Sinari, Shripad A.; Tembe, Waibhav D.; Haussler, David; Hinrichs, Angie S.; Katzman, Sol J.; Kern, Andrew; Kuhn, Robert M.; Przeworski, Molly; Hernandez, Ryan D.; Howie, Bryan; Kelley, Joanna L.; Melton, S. Cord; Abecasis, Gonçalo R.; Li, Yun; Anderson, Paul; Blackwell, Tom; Chen, Wei; Cookson, William O.; Ding, Jun; Kang, Hyun Min; Lathrop, Mark; Liang, Liming; Moffatt, Miriam F.; Scheet, Paul; Sidore, Carlo; Snyder, Matthew; Zhan, Xiaowei; Zöllner, Sebastian; Awadalla, Philip; Casals, Ferran; Idaghdour, Youssef; Keebler, John; Stone, Eric A.; Zilversmit, Martine; Jorde, Lynn; Xing, Jinchuan; Eichler, Evan E.; Aksay, Gozde; Alkan, Can; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Kidd, Jeffrey M.; Sahinalp, S. Cenk; Sudmant, Peter H.; Mardis, Elaine R.; Chen, Ken; Chinwalla, Asif; Ding, Li; Koboldt, Daniel C.; McLellan, Mike D.; Dooling, David; Weinstock, George; Wallis, John W.; Wendl, Michael C.; Zhang, Qunyuan; Durbin, Richard M.; Albers, Cornelis A.; Ayub, Qasim; Balasubramaniam, Senduran; Barrett, Jeffrey C.; Carter, David M.; Chen, Yuan; Conrad, Donald F.; Danecek, Petr; Dermitzakis, Emmanouil T.; Hu, Min; Huang, Ni; Hurles, Matt E.; Jin, Hanjun; Jostins, Luke; Keane, Thomas M.; Le, Si Quang; Lindsay, Sarah; Long, Quan; MacArthur, Daniel G.; Montgomery, Stephen B.; Parts, Leopold; Stalker, James; Tyler-Smith, Chris; Walter, Klaudia; Zhang, Yujun; Gerstein, Mark B.; Snyder, Michael; Abyzov, Alexej; Balasubramanian, Suganthi; Bjornson, Robert; Du, Jiang; Grubert, Fabian; Habegger, Lukas; Haraksingh, Rajini; Jee, Justin; Khurana, Ekta; Lam, Hugo Y. K.; Leng, Jing; Mu, Xinmeng Jasmine; Urban, Alexander E.; Zhang, Zhengdong; Li, Yingrui; Luo, Ruibang; Marth, Gabor T.; Garrison, Erik P.; Kural, Deniz; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; McCarroll, Steven A.; Banks, Eric; DePristo, Mark A.; Handsaker, Robert E.; Hartl, Chris; Korn, Joshua M.; Li, Heng; Nemesh, James C.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Degenhardt, Jeremiah; Kaganovich, Mark; Clarke, Laura; Smith, Richard E.; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Humphray, Sean; Cheetham, R. Keira; Eberle, Michael; Kahn, Scott; Murray, Lisa; Ye, Kai; De La Vega, Francisco M.; Fu, Yutao; Peckham, Heather E.; Sun, Yongming A.; Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.; Xiao, Chunlin; Iqbal, Zamin; Desany, Brian; Blackwell, Tom; Snyder, Matthew; Xing, Jinchuan; Eichler, Evan E.; Aksay, Gozde; Alkan, Can; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Kidd, Jeffrey M.; Chen, Ken; Chinwalla, Asif; Ding, Li; McLellan, Mike D.; Wallis, John W.; Hurles, Matt E.; Conrad, Donald F.; Walter, Klaudia; Zhang, Yujun; Gerstein, Mark B.; Snyder, Michael; Abyzov, Alexej; Du, Jiang; Grubert, Fabian; Haraksingh, Rajini; Jee, Justin; Khurana, Ekta; Lam, Hugo Y. K.; Leng, Jing; Mu, Xinmeng Jasmine; Urban, Alexander E.; Zhang, Zhengdong; Gibbs, Richard A.; Bainbridge, Matthew; Challis, Danny; Coafra, Cristian; Dinh, Huyen; Kovar, Christie; Lee, Sandy; Muzny, Donna; Nazareth, Lynne; Reid, Jeff; Sabo, Aniko; Yu, Fuli; Yu, Jin; Marth, Gabor T.; Garrison, Erik P.; Indap, Amit; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Ward, Alistair N.; Wu, Jiantao; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Garimella, Kiran V.; Hartl, Chris; Shefler, Erica; Sougnez, Carrie L.; Wilkinson, Jane; Clark, Andrew G.; Gravel, Simon; Grubert, Fabian; Clarke, Laura; Flicek, Paul; Smith, Richard E.; Zheng-Bradley, Xiangqun; Sherry, Stephen T.; Khouri, Hoda M.; Paschall, Justin E.; Shumway, Martin F.; Xiao, Chunlin; McVean, Gil A.; Katzman, Sol J.; Abecasis, Gonçalo R.; Blackwell, Tom; Mardis, Elaine R.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Koboldt, Daniel C.; Durbin, Richard M.; Balasubramaniam, Senduran; Coffey, Allison; Keane, Thomas M.; MacArthur, Daniel G.; Palotie, Aarno; Scott, Carol; Stalker, James; Tyler-Smith, Chris; Gerstein, Mark B.; Balasubramanian, Suganthi; Chakravarti, Aravinda; Knoppers, Bartha M.; Abecasis, Gonçalo R.; Bustamante, Carlos D.; Gharani, Neda; Gibbs, Richard A.; Jorde, Lynn; Kaye, Jane S.; Kent, Alastair; Li, Taosha; McGuire, Amy L.; McVean, Gil A.; Ossorio, Pilar N.; Rotimi, Charles N.; Su, Yeyang; Toji, Lorraine H.; TylerSmith, Chris; Brooks, Lisa D.; Felsenfeld, Adam L.; McEwen, Jean E.; Abdallah, Assya; Juenger, Christopher R.; Clemm, Nicholas C.; Collins, Francis S.; Duncanson, Audrey; Green, Eric D.; Guyer, Mark S.; Peterson, Jane L.; Schafer, Alan J.; Abecasis, Gonçalo R.; Altshuler, David L.; Auton, Adam; Brooks, Lisa D.; Durbin, Richard M.; Gibbs, Richard A.; Hurles, Matt E.; McVean, Gil A.

    2011-01-01

    High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence. PMID:21730125

  1. Naturally occurring allele diversity allows potato cultivation in northern latitudes.

    Science.gov (United States)

    Kloosterman, Bjorn; Abelenda, José A; Gomez, María del Mar Carretero; Oortwijn, Marian; de Boer, Jan M; Kowitwanich, Krissana; Horvath, Beatrix M; van Eck, Herman J; Smaczniak, Cezary; Prat, Salomé; Visser, Richard G F; Bachem, Christian W B

    2013-03-14

    Potato (Solanum tuberosum L.) originates from the Andes and evolved short-day-dependent tuber formation as a vegetative propagation strategy. Here we describe the identification of a central regulator underlying a major-effect quantitative trait locus for plant maturity and initiation of tuber development. We show that this gene belongs to the family of DOF (DNA-binding with one finger) transcription factors and regulates tuberization and plant life cycle length, by acting as a mediator between the circadian clock and the StSP6A mobile tuberization signal. We also show that natural allelic variants evade post-translational light regulation, allowing cultivation outside the geographical centre of origin of potato. Potato is a member of the Solanaceae family and is one of the world's most important food crops. This annual plant originates from the Andean regions of South America. Potato develops tubers from underground stems called stolons. Its equatorial origin makes potato essentially short-day dependent for tuberization and potato will not make tubers in the long-day conditions of spring and summer in the northern latitudes. When introduced in temperate zones, wild material will form tubers in the course of the autumnal shortening of day-length. Thus, one of the first selected traits in potato leading to a European potato type is likely to have been long-day acclimation for tuberization. Potato breeders can exploit the naturally occurring variation in tuberization onset and life cycle length, allowing varietal breeding for different latitudes, harvest times and markets. PMID:23467094

  2. A unique skeletal microstructure of the deep-sea micrabaciid scleractinian corals

    Science.gov (United States)

    Janiszewska, Katarzyna; Stolarski, Jaroslaw; Benzerara, Karim; Meibom, Anders; Mazur, Maciej; Kitahara, Marcelo; Cairns, Stephen D.

    2010-05-01

    separated at the meso-scale. However, AFM and FESEM observations of RAD show nanogranular units (ca. 30-100 nm in diameter) typical of fast growing skeletal regions. Unique microstructural organization of the micrabaciid skeleton supports their monophyletic status (reinforced by macromorphological and molecular data), and points to a diversity of organic matrix-mediated biomineralization strategies in Scleractinia.

  3. Calsequestrins in skeletal and cardiac muscle from adult Danio rerio.

    Science.gov (United States)

    Furlan, Sandra; Mosole, Simone; Murgia, Marta; Nagaraj, Nagarjuna; Argenton, Francesco; Volpe, Pompeo; Nori, Alessandra

    2016-04-01

    Calsequestrin (Casq) is a high capacity, low affinity Ca(2+)-binding protein, critical for Ca(2+)-buffering in cardiac and skeletal muscle sarcoplasmic reticulum. All vertebrates have multiple genes encoding for different Casq isoforms. Increasing interest has been focused on mammalian and human Casq genes since mutations of both cardiac (Casq2) and skeletal muscle (Casq1) isoforms cause different, and sometime severe, human pathologies. Danio rerio (zebrafish) is a powerful model for studying function and mutations of human proteins. In this work, expression, biochemical properties cellular and sub-cellular localization of D. rerio native Casq isoforms are investigated. By quantitative PCR, three mRNAs were detected in skeletal muscle and heart with different abundances. Three zebrafish Casqs: Casq1a, Casq1b and Casq2 were identified by mass spectrometry (Data are available via ProteomeXchange with identifier PXD002455). Skeletal and cardiac zebrafish calsequestrins share properties with mammalian Casq1 and Casq2. Skeletal Casqs were found primarily, but not exclusively, at the sarcomere Z-line level where terminal cisternae of sarcoplasmic reticulum are located. PMID:26585961

  4. Estimation of skeletal muscle mass from body creatine content

    Science.gov (United States)

    Pace, N.; Rahlmann, D. F.

    1982-01-01

    Procedures have been developed for studying the effect of changes in gravitational loading on skeletal muscle mass through measurements of the body creatine content. These procedures were developed for studies of gravitational scale effects in a four-species model, comprising the hamster, rat, guinea pig, and rabbit, which provides a sufficient range of body size for assessment of allometric parameters. Since intracellular muscle creatine concentration varies among species, and with age within a given species, the concentration values for metabolically mature individuals of these four species were established. The creatine content of the carcass, skin, viscera, smooth muscle, and skeletal muscle was determined for each species. In addition, the skeletal muscle mass of the major body components was determined, as well as the total and fat-free masses of the body and carcass, and the percent skeletal muscle in each. It is concluded that these procedures are particularly useful for studying the effect of gravitational loading on the skeletal muscle content of the animal carcass, which is the principal weight-bearing organ of the body.

  5. Prolonged Culture of Aligned Skeletal Myotubes on Micromolded Gelatin Hydrogels

    Science.gov (United States)

    Bettadapur, Archana; Suh, Gio C.; Geisse, Nicholas A.; Wang, Evelyn R.; Hua, Clara; Huber, Holly A.; Viscio, Alyssa A.; Kim, Joon Young; Strickland, Julie B.; McCain, Megan L.

    2016-06-01

    In vitro models of skeletal muscle are critically needed to elucidate disease mechanisms, identify therapeutic targets, and test drugs pre-clinically. However, culturing skeletal muscle has been challenging due to myotube delamination from synthetic culture substrates approximately one week after initiating differentiation from myoblasts. In this study, we successfully maintained aligned skeletal myotubes differentiated from C2C12 mouse skeletal myoblasts for three weeks by utilizing micromolded (μmolded) gelatin hydrogels as culture substrates, which we thoroughly characterized using atomic force microscopy (AFM). Compared to polydimethylsiloxane (PDMS) microcontact printed (μprinted) with fibronectin (FN), cell adhesion on gelatin hydrogel constructs was significantly higher one week and three weeks after initiating differentiation. Delamination from FN-μprinted PDMS precluded robust detection of myotubes. Compared to a softer blend of PDMS μprinted with FN, myogenic index, myotube width, and myotube length on μmolded gelatin hydrogels was similar one week after initiating differentiation. However, three weeks after initiating differentiation, these parameters were significantly higher on μmolded gelatin hydrogels compared to FN-μprinted soft PDMS constructs. Similar results were observed on isotropic versions of each substrate, suggesting that these findings are independent of substrate patterning. Our platform enables novel studies into skeletal muscle development and disease and chronic drug testing in vitro.

  6. Extra-osseous uterine pathophysiology demonstrated on skeletal scintigraphy

    International Nuclear Information System (INIS)

    Full text: Skeletal scintigraphy is a sensitive procedure for evaluating disease and trauma involving the skeleton. Extra-skeletal pathophysiology is also often demonstrated. This may include uptake by tumours, soft tissue calcification and infection as well as renal pathology. Skeletal scintigraphy is often performed to evaluate hip and back pain and extra-osseous uterine pathophysiology can be demonstrated in both the early and late phases of the study as in the following cases. Three women underwent skeletal scintigraphy for the investigation of low back pain in two patients and post-partum hip pain in one. A large vascular uterus with deviation of the bladder was demonstrated in the post-partum patient. Increased pelvic vascularity and bladder deviation in the second patient was shown by ultrasound to correspond to a left-sided fibroid with associated adenomyosis. In the third case, right-sided pelvic vascularity and left bladder deviation were shown on ultrasound to be due to an anteverted, anteflexed uterus tilted to the right. These cases illustrate the importance of documenting extra-osseous findings on skeletal scintigraphy and the benefits of correlation with anatomical imaging

  7. Thalidomide affects the skeletal system of ovariectomized rats.

    Science.gov (United States)

    Kaczmarczyk-Sedlak, Ilona; Folwarczna, Joanna; Trzeciak, Henryk I

    2009-01-01

    Apart from having written an inglorious chapter in the history of medicine, thalidomide is currently being intensely studied because of its multidimensional activity. The aim of this study was to examine the effects of thalidomide on the skeletal system in ovariectomized and non-ovariectomized rats. The experiments were carried out with female Wistar rats, divided into eight groups: sham-operated control rats; sham-operated rats receiving thalidomide at doses of 15, 30 or 60 mg/kg, po; ovariectomized control rats; ovariectomized rats receiving thalidomide at doses of 15, 30 or 60 mg/kg, po. The drug was administered for 4 weeks. Body mass gain and the mass of the uterus, liver, spleen and thymus were studied. Macrometric parameters and content of mineral substances, calcium and phosphorus in the femur, tibia and L-4 vertebra and histomorphometric parameters of the femur and tibia were examined. In the femur, the mechanical properties of the whole bone and of the femoral neck were examined. Thalidomide did not affect the skeletal system of the non-ovariectomized rats. Bilateral ovariectomy induced osteoporotic skeletal changes in mature female rats. The effects of thalidomide on the skeletal system of ovariectomized rats depended on the dose used. With a dose of 15 mg/kg, po, thalidomide counteracted some osteoporotic changes induced by estrogen deficiency. With a dose of 60 mg/kg, po, thalidomide intensified the destructive effects of estrogen deficiency on the rat skeletal system.

  8. Follow-up skeletal survey use by child abuse pediatricians.

    Science.gov (United States)

    Harper, Nancy S; Lewis, Terri; Eddleman, Sonja; Lindberg, Daniel M

    2016-01-01

    Skeletal survey is frequently used to identify occult fractures in young children with concern for physical abuse. Because skeletal survey is relatively insensitive for some abusive fractures, a follow-up skeletal survey (FUSS) may be undertaken at least 10-14 days after the initial skeletal survey to improve sensitivity for healing fractures. This was a prospectively planned secondary analysis of a prospective, observational study of 2,890 children who underwent subspecialty evaluation for suspected child physical abuse at 1 of 19 centers. Our objective was to determine variability between sites in rates of FUSS recommendation, completion and fracture identification among the 2,049 participants who had an initial SS. Among children with an initial skeletal survey, the rate of FUSS recommendation for sites ranged from 20% to 97%; the rate of FUSS completion ranged from 10% to 100%. Among sites completing at least 10 FUSS, rates of new fracture identification ranged from 8% to 28%. Among completed FUSS, new fractures were more likely to be identified in younger children, children with higher initial level of concern for abuse, and those with a fracture or cutaneous injury identified in the initial evaluation. The current variability in FUSS utilization is not explained by variability in occult fracture prevalence. Specific guidelines for FUSS utilization are needed. PMID:26342432

  9. The effects of obesity on skeletal muscle regeneration

    Directory of Open Access Journals (Sweden)

    Dmitry eAkhmedov

    2013-12-01

    Full Text Available Obesity and metabolic disorders such as type 2 diabetes mellitus are accompanied by increased lipid deposition in adipose and non-adipose tissues including liver, pancreas, heart and skeletal muscle. Recent publications report impaired regenerative capacity of skeletal muscle following injury in obese mice. Although muscle regeneration has not been thoroughly studied in obese and type 2 diabetic humans and mechanisms leading to decreased muscle regeneration in obesity remain elusive, the initial findings point to the possibility that muscle satellite cell function is compromised under conditions of lipid overload. Elevated toxic lipid metabolites and increased proinflammatory cytokines as well as insulin and leptin resistance that occur in obese animals may contribute to decreased regenerative capacity of skeletal muscle. In addition, obesity-associated alterations in the metabolic state of skeletal muscle fibers and satellite cells may directly impair the potential for satellite cell-mediated repair. Here we discuss recent studies that expand our understanding of how obesity negatively impacts skeletal muscle maintenance and regeneration.

  10. Does I-131-MIBG underestimate skeletal disease burden in neuroblastoma?

    Directory of Open Access Journals (Sweden)

    Barai Sukanta

    2004-10-01

    Full Text Available Background: Controversy persists as to the need for both MIBG and bone scanning in routine evaluation of neuroblastoma. Aim: To compare the efficacy of I-131- metaiodobenzylguanidine (MIBG scan against that of conventional Tc99m- methylene diphosphonate (MDP bone scan for the detection of skeletal deposition of neuroblastoma. Methods and Material: The study included 57 patients (36 boys, 21 girls: age range 1-14 years of neuroblastoma who underwent both bone scan with Tc99m-MDP and I-131-MIBG scan within 15 days of each other at presentation and during follow-up. Results: At presentation 11(19.2% patients had evidence of skeletal metastases on MDP scan against 7 patients who showed bony secondaries on MIBG scan. Of the 7 patients, with positive MIBG and MDP scans, MDP scan detected 11 sites whereas MIBG scan detected 7 sites. On follow-up study, 3 patients with initial abnormal MDP scan but normal MIBG scan, developed skeletal metastases detectable on MIBG scan, whereas 3 of the 46 patients who had normal MDP and MIBG scan at presentation; developed skeletal metastases detectable on MDP scan. MIBG scan was concordant in 2 of them but was normal in the third patient. Conclusion: I-131-MIBG underestimates skeletal disease burden in neuroblastoma. Therefore, Tc99m-MDP bone scan should remain a part of routine assessment of patients with neuroblastoma.

  11. Osteopoikilosis: A Sign Mimicking Skeletal Metastases in a Cancer Patient

    Directory of Open Access Journals (Sweden)

    Hamid Nasrolahi

    2011-01-01

    Full Text Available Osteopoikilosis is a rare benign osteosclerotic bone disorder that may be misdiagnosed as skeletal metastases. Here we describe a case of coincidental breast cancer and osteopoikilosis mimicking skeletal metastases. A 41-year-old woman underwent right modified radical mastectomy in April 2007. Twenty-eight months after initial treatment,the patient complained of bilateral knee and foot pain. Plain X-rays of the feet and knees showed multiple well-defined osteosclerotic lesions. According to the radiographic appearance, the most likely differential diagnoses included skeletal metastases from breast cancer and osteopoikilosis. A whole-body bone scintigraphy showed no increase in uptake by the sclerotic lesions, and serum lactic dehydrogenase, carcinoembryonic antigen, alkaline phosphatase and cancer antigen 15-3 were not elevated. We therefore diagnosed the patient’s skeletal lesions as osteopoikilosis. This case and ourliterature review suggest that the radiographic appearance of osteopoikilosis may mimic or mask skeletal metastases, potentially leading to misdiagnosis in patients with cancer.

  12. Diversity of HLA-B17 alleles and haplotypes in East Asians and a novel Cw6 allele (Cw*0604) associated with B*5701.

    Science.gov (United States)

    Inoue, T; Ogawa, A; Tokunaga, K; Ishikawa, Y; Kashiwase, K; Tanaka, H; Park, M H; Jia, G J; Chimge, N O; Sideltseva, E W; Akaza, T; Tadokoro, K; Takahashi, T; Juji, T

    1999-06-01

    The distribution of HLA-B17 alleles and their association with HLA-A, -C and -DRB1 alleles were investigated in seven East Asian populations Japanese, South Korean, Chinese-Korean, Man, Northern Han, Mongolian and Buryat populations). The B17 alleles were identified from genomic DNA using group-specific polymerase chain reaction (PCR) followed by hybridization with sequence-specific oligonucleotide probes (SSOP). In all of these East Asian populations, except Japanese and Chinese-Koreans, B*5701 was detected and strongly associated with A*0101, Cw*0602 and DRB1*0701. In contrast, B*5801 was detected in all the seven populations and strongly associated with A*3303, Cw*0302, DRB1*0301 and DRB1*1302. The A*3303-Cw*0302-B*5801-DRB1*1302 haplotype was observed in South Korean, Chinese-Korean, Buryat and Japanese populations, while A*3303-Cw*0302-B*5801-DRB1*0301 was predominantly observed in the Mongolian population. A similar haplotype, A*0101-Cw*0302-B*5801-DRB1*1302, was observed in the Buryat population. A novel Cw6 allele, Cw*0604, was identified in the Man population. This Cw allele was observed on the haplotype A*0101-B*5701-DRB1*0701. Thus, we confirmed, at the sequence level, that the common haplotypes carrying B*5701 and B*5801 have been conserved and shared in East Asian populations.

  13. Separably injective Banach spaces

    CERN Document Server

    Avilés, Antonio; Castillo, Jesús M F; González, Manuel; Moreno, Yolanda

    2016-01-01

    This monograph contains a detailed exposition of the up-to-date theory of separably injective spaces: new and old results are put into perspective with concrete examples (such as l∞/c0 and C(K) spaces, where K is a finite height compact space or an F-space, ultrapowers of L∞ spaces and spaces of universal disposition). It is no exaggeration to say that the theory of separably injective Banach spaces is strikingly different from that of injective spaces. For instance, separably injective Banach spaces are not necessarily isometric to, or complemented subspaces of, spaces of continuous functions on a compact space. Moreover, in contrast to the scarcity of examples and general results concerning injective spaces, we know of many different types of separably injective spaces and there is a rich theory around them. The monograph is completed with a preparatory chapter on injective spaces, a chapter on higher cardinal versions of separable injectivity and a lively discussion of open problems and further lines o...

  14. Organic Separation Test Results

    Energy Technology Data Exchange (ETDEWEB)

    Russell, Renee L.; Rinehart, Donald E.; Peterson, Reid A.

    2014-09-22

    Separable organics have been defined as “those organic compounds of very limited solubility in the bulk waste and that can form a separate liquid phase or layer” (Smalley and Nguyen 2013), and result from three main solvent extraction processes: U Plant Uranium Recovery Process, B Plant Waste Fractionation Process, and Plutonium Uranium Extraction (PUREX) Process. The primary organic solvents associated with tank solids are TBP, D2EHPA, and NPH. There is concern that, while this organic material is bound to the sludge particles as it is stored in the tanks, waste feed delivery activities, specifically transfer pump and mixer pump operations, could cause the organics to form a separated layer in the tank farms feed tank. Therefore, Washington River Protection Solutions (WRPS) is experimentally evaluating the potential of organic solvents separating from the tank solids (sludge) during waste feed delivery activities, specifically the waste mixing and transfer processes. Given the Hanford Tank Waste Treatment and Immobilization Plant (WTP) waste acceptance criteria per the Waste Feed Acceptance Criteria document (24590-WTP-RPT-MGT-11-014) that there is to be “no visible layer” of separable organics in the waste feed, this would result in the batch being unacceptable to transfer to WTP. This study is of particular importance to WRPS because of these WTP requirements.

  15. Gulf stream separation dynamics

    Science.gov (United States)

    Schoonover, Joseph

    Climate models currently struggle with the more traditional, coarse ( O(100 km) ) representation of the ocean. In these coarse ocean simulations, western boundary currents are notoriously difficult to model accurately. The modeled Gulf Stream is typically seen exhibiting a mean pathway that is north of observations, and is linked to a warm sea-surface temperature bias in the Mid-Atlantic Bight. Although increased resolution ( O(10 km) ) improves the modeled Gulf Stream position, there is no clean recipe for obtaining the proper pathway. The 70 year history of literature on the Gulf Stream separation suggests that we have not reached a resolution on the dynamics that control the current's pathway just south of the Mid-Atlantic Bight. Without a concrete knowledge on the separation dynamics, we cannot provide a clean recipe for accurately modeling the Gulf Stream at increased resolutions. Further, any reliable parameterization that yields a realistic Gulf Stream path must express the proper physics of separation. The goal of this dissertation is to determine what controls the Gulf Stream separation. To do so, we examine the results of a model intercomparison study and a set of numerical regional terraforming experiments. It is argued that the separation is governed by local dynamics that are most sensitive to the steepening of the continental shelf, consistent with the topographic wave arrest hypothesis of Stern (1998). A linear extension of Stern's theory is provided, which illustrates that wave arrest is possible for a continuously stratified fluid.

  16. Allelic discrimination in naturalized ovine from Pantanal Sul-Matogrossense by means of microsatellite markers

    Directory of Open Access Journals (Sweden)

    Crispim Bruno do Amaral

    2012-08-01

    Full Text Available The molecular biology techniques that are used in allelic discrimination for individual and sheep breeds characterization are important tools in breeding programs and conservation of genetic resources. The use of microsatellite markers allows allelic differentiation, which in turn allows us to infer the genetic variability of sample populations. The study aimed to test the sensitivity and efficiency of fluorescent capillary electrophoresis, using microsatellite primers, for allelic discrimination of the Crioulo breed from Pantanal sul-matogrossense, as well as verify the possibility of using the products of sequencing in genetic variability analysis. For this test, were used blood samples from Pantaneira breed sheep. The allelic discrimination of eight microsatellites was determined by capillary electrophoresis in automatic sequencer and the results analyses were performed on the programs CERVUS and Dendro-UPGMA. The results indicated the possibility of using this technique for the individual genotyping of all loci tested in electrophoretic analysis and its potential to allelic discrimination even in case of difference between two pairs of bases between the alleles. The resulting dendrogram based on the distance matrix by the UPGMA assembly method, indicated medium similarity coefficient of 0.72 in the group of animals. It was concluded that there is the viability and efficiency of the microsatellite molecular markers technique using capillary electrophoresis for allelic discrimination and the utility of results for studies of genetic variability, paternity diagnosis and characterization of the Crioulo sheep herd from Pantanal sul-matogrossense.

  17. Correlation of DNA fragment sizes within loci in the presence of non-detectable alleles.

    Science.gov (United States)

    Chakraborty, R; Li, Z

    1995-01-01

    At present most forensic databases of DNA profiling of individuals consist of DNA fragment sizes measured from Southern blot restriction fragment length polymorphism (RFLP) analysis. Statistical studies of these databases have revealed that, when fragment sizes are measured from RFLP analysis, some of the single-band patterns of individuals may actually be due to heterozygosity of alleles in which fragment size resulting from one allele remains undetected. In this work, we evaluate the effect of such allelic non-detectability on correlation of fragment sizes within individuals at a locus, and its impact on the inference of independence of fragment sizes within loci. We show that when non-detectable alleles are present in a population at a locus, positive correlations of fragment sizes are expected, which increase with the proportion of non-detectable alleles at the locus. Therefore, a non-zero positive correlation is not a proof of allelic dependence within individuals. Applications of this theory to the current forensic RFLP databases within the US show that there is virtually no evidence of significant allelic dependence within any of the loci. Therefore, the assumption that DNA fragment sizes within loci are independent is valid, and hence, the population genetic principles of computing DNA profile frequencies by multiplying binned frequencies of fragment sizes are most likely to be appropriate for forensic applications of DNA typing data.

  18. Mass Separation by Metamaterials.

    Science.gov (United States)

    Restrepo-Flórez, Juan Manuel; Maldovan, Martin

    2016-02-25

    Being able to manipulate mass flow is critically important in a variety of physical processes in chemical and biomolecular science. For example, separation and catalytic systems, which requires precise control of mass diffusion, are crucial in the manufacturing of chemicals, crystal growth of semiconductors, waste recovery of biological solutes or chemicals, and production of artificial kidneys. Coordinate transformations and metamaterials are powerful methods to achieve precise manipulation of molecular diffusion. Here, we introduce a novel approach to obtain mass separation based on metamaterials that can sort chemical and biomolecular species by cloaking one compound while concentrating the other. A design strategy to realize such metamaterial using homogeneous isotropic materials is proposed. We present a practical case where a mixture of oxygen and nitrogen is manipulated using a metamaterial that cloaks nitrogen and concentrates oxygen. This work lays the foundation for molecular mass separation in biophysical and chemical systems through metamaterial devices.

  19. Mass Separation by Metamaterials

    Science.gov (United States)

    Restrepo-Flórez, Juan Manuel; Maldovan, Martin

    2016-02-01

    Being able to manipulate mass flow is critically important in a variety of physical processes in chemical and biomolecular science. For example, separation and catalytic systems, which requires precise control of mass diffusion, are crucial in the manufacturing of chemicals, crystal growth of semiconductors, waste recovery of biological solutes or chemicals, and production of artificial kidneys. Coordinate transformations and metamaterials are powerful methods to achieve precise manipulation of molecular diffusion. Here, we introduce a novel approach to obtain mass separation based on metamaterials that can sort chemical and biomolecular species by cloaking one compound while concentrating the other. A design strategy to realize such metamaterial using homogeneous isotropic materials is proposed. We present a practical case where a mixture of oxygen and nitrogen is manipulated using a metamaterial that cloaks nitrogen and concentrates oxygen. This work lays the foundation for molecular mass separation in biophysical and chemical systems through metamaterial devices.

  20. Allelic variation in the squirrel monkey x-linked color vision gene: biogeographical and behavioral correlates.

    Science.gov (United States)

    Cropp, Susan; Boinski, Sue; Li, Wen-Hsiung

    2002-06-01

    Most Neotropical primate species possess a polymorphic X-linked and a monomorphic autosomal color vision gene. Consequently, populations are composed of both dichromatics and trichromatics. Most theories on the maintenance of this genetic system revolve around possible advantages for foraging ecology. To examine the issue from a different angle, we compared the numbers and relative frequencies of alleles at the X-linked locus among three species of Saimiri representing a wide range of geographical and behavioral variation in the genus. Exons 3, 4, and 5 of the X-linked opsin gene were sequenced for a large number of X chromosomes for all three species. Several synonymous mutations were detected in exons 4 and 5 for the originally reported alleles but only a single nonsynonymous change was detected. Two alleles were found that appeared to be the result of recombination events. The low occurrence of recombinant alleles and absence of mutations in the amino acids critical for spectral tuning indicates that stabilizing selection acts to maintain the combinations of critical sites specific to each allele. Allele frequencies were approximately the same for all Saimiri species, with a slight but significant difference between S. boliviensis and S. oerstedii. No apparent correlation exists between allele frequencies and behavioral or biogeographical differences between species, casting doubt on the speculation that the spectral sensitivities of the alleles have been maintained because they are specifically well-tuned to Saimiri visual ecology. Rather, the spectral tuning peaks might have been maintained because they are as widely spaced as possible within the limited range of middlewave to longwave spectra useful to all primates. This arrangement creates a balance between maximizing the distance between spectral tuning peaks (allowing the color opponency of the visual system to distinguish between peaks) and maximizing the number of alleles within a limited range (yielding

  1. Multiple origins of Plasmodium falciparum dihydropteroate synthetase mutant alleles associated with sulfadoxine resistance in India.

    Science.gov (United States)

    Lumb, Vanshika; Das, Manoj K; Singh, Neeru; Dev, Vas; Khan, Wajihullah; Sharma, Yagya D

    2011-06-01

    With the spread of chloroquine (CQ)-resistant malaria in India, sulfadoxine-pyrimethamine (SP) alone or in combination with artesunate is used as an alternative antimalarial drug. Due to continuous drug pressure, the Plasmodium falciparum parasite is exhibiting resistance to antifolates because of mutations in candidate genes dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps). Our earlier study on flanking microsatellite markers of dhfr mutant alleles from India had shown a single origin of the pyrimethamine resistance and some minor haplotypes which shared haplotypes with Southeast Asian (Thailand) strains. In the present study, we have analyzed 193 of these Indian P. falciparum isolates for 15 microsatellite loci around dhps to investigate the genetic lineages of the mutant dhps alleles in different parts of the country. Eighty-one of these samples had mutant dhps alleles, of which 62 were from Andaman and Nicobar Islands and the remaining 19 were from mainland India. Of 112 isolates with a wild-type dhps allele, 109 were from mainland India and only 3 were from Andaman and Nicobar Islands. Consistent with the model of selection, the mean expected heterozygosity (H(e)) around mutant dhps alleles (H(e) = 0.55; n = 81) associated with sulfadoxine resistance was lower (P ≤ 0.05) than the mean H(e) around the wild-type dhps allele (H(e) = 0.80; n = 112). There was more genetic diversity in flanking microsatellites of dhps than dhfr among these isolates, which confirms the assertion that dhps mutations are at a very early stage of fixation in the parasite population. Microsatellite haplotypes around various mutant dhps alleles suggest that the resistant dhps alleles have multiple independent origins in India, especially in Andaman and Nicobar Islands. Determining the genetic lineages of the resistant dhps alleles on Andaman and Nicobar Islands and mainland India is significant, given the role of Asia in the intercontinental spread of chloroquine

  2. Global pathway analysis using DNA microarrays in skeletal muscle of women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe

    2007-01-01

    . The spots were well separated on the chips and had satisfactory spot morphology. The linear range was three orders of magnitude. In a series of self-hybridization experiments, we demonstrated a low coefficient of variation (CV) and high precision and accuracy of the chips. Conclusions These data indicate...... that impaired expression of genes representing OXPHOS pathways may play a role for insulin resistance in skeletal muscle of women with PCOS. Upregulation of OXPHOS pathways seems to be one of the mechanisms whereby pioglitazone improves insulin sensitivity. Our in-house spotted microarray chip performed...... comparable to other commercial and custom made microarrays and is a cost-effective alternative especially in larger epidemiological studies....

  3. Metabolic alkalosis reduces exercise-induced acidosis and potassium accumulation in human skeletal muscle interstitium

    DEFF Research Database (Denmark)

    Street, D.; Nielsen, Jens Jung; Bangsbo, Jens;

    2005-01-01

    Skeletal muscle releases potassium during activity. Interstitial potassium accumulation is important for muscle function and the development of fatigue resulting from exercise. In the present study we used sodium citrate ingestion as a tool to investigate the relationship between interstitial H......+ concentration and K+ accumulation during exercise. Seven healthy subjects performed one-legged knee-extensor exercise on two separate days with and without sodium citrate ingestion. Interstitial H+ and K+ concentrations were measured with the microdialysis technique. Citrate ingestion reduced the plasma H......+ concentration and increased the plasma HCO3- concentration. Citrate had no effect on interstitial H+ at rest. The increase in interstitial H+ concentration during intense exercise was significantly lower (P citrate ingestion compared to control (peak interstitial H+ concentration 79 versus 131 n...

  4. Identification of 2127 new HLA class I alleles in potential stem cell donors from Germany, the United States and Poland.

    Science.gov (United States)

    Hernández-Frederick, C J; Giani, A S; Cereb, N; Sauter, J; Silva-González, R; Pingel, J; Schmidt, A H; Ehninger, G; Yang, S Y

    2014-03-01

    We describe 2127 new human leukocyte antigen (HLA) class I alleles found in registered stem cell donors. These alleles represent 28.9% of the currently known class I alleles. Comparing new allele sequences to homologous sequences, we found 68.1% nonsynonymous nucleotide substitutions, 28.9% silent mutations and 3.0% nonsense mutations. Many substitutions occurred at positions that have not been known to be polymorphic before. A large number of HLA alleles and nucleotide variations underline the extreme diversity of the HLA system. Strikingly, 156 new alleles were found not only multiple times, but also in carriers of various parentage, suggesting that some new alleles are not necessarily rare. Moreover, new alleles were found especially often in minority donors. This emphasizes the benefits of specifically recruiting such groups of individuals.

  5. Analysis of a Larger SNP Dataset from the HapMap Project Confirmed That the Modern Human A Allele of the ABO Blood Group Genes Is a Descendant of a Recombinant between B and O Alleles

    Directory of Open Access Journals (Sweden)

    Masaya Itou

    2013-01-01

    Full Text Available The human ABO blood group gene consists of three main alleles (A, B, and O that encode a glycosyltransferase. The A and B alleles differ by two critical amino acids in exon 7, and the major O allele has a single nucleotide deletion (Δ261 in exon 6. Previous evolutionary studies have revealed that the A allele is the most ancient, B allele diverged from the A allele with two critical amino acid substitutions in exon 7, and the major O allele diverged from the A allele with Δ261 in exon 6. However, a recent phylogenetic network analysis study showed that the A allele of humans emerged through a recombination between the B and O alleles. In the previous study, a restricted dataset from only two populations was used. In this study, therefore, we used a large single nucleotide polymorphism (SNP dataset from the HapMap Project. The results indicated that the A101-A201-O09 haplogroup was a recombinant lineage between the B and O haplotypes, containing the intact exon 6 from the B allele and the two critical A type sites in exon 7 from the major O allele. Its recombination point was assumed to be located just behind Δ261 in exon 6.

  6. Skeletal structure of printed words: evidence from the stroop task.

    Science.gov (United States)

    Berent, Iris; Marom, Michal

    2005-04-01

    Do readers encode the sequencing of consonant (C) and vowel (V) phonemes (skeletal structure) in printed words? The authors used the Stroop task to examine readers' sensitivity to skeletal structure. In Experiment 1, CVC nonwords (e.g., pof) facilitated the naming of colors with congruent frames (e.g., red, a CVC word) but not with incongruent ones (e.g., green). In Experiment 2, the color black (a CCVC frame) was named faster with a congruent CCVC frame (e.g., grof) compared to either CCVCC (e.g., groft) or CVC (e.g., gof) incongruent controls. Finally, in Experiment 3, the color pink (a CVCC frame) was named faster with a CVCC frame (e.g., goft) compared to either CCVCC or CVC incongruent controls. In most cases, congruent frames shared no segments with the color name. These findings demonstrate that readers automatically assemble the skeletal structure of printed words.

  7. Skeletal response to simulated weightlessness - A comparison of suspension techniques

    Science.gov (United States)

    Wronski, T. J.; Morey-Holton, E. R.

    1987-01-01

    Comparisons are made of the skeletal response of rats subjected to simulated weightlessness by back or tail suspension. In comparison to pair-fed control rats, back-suspended rats failed to gain weight whereas tail-suspended rats exhibited normal weight gain. Quantitative bone histomorphometry revealed marked skeletal abnormalities in the proximal tibial metaphysis of back-suspended rats. Loss of trabecular bone mass in these animals was due to a combination of depressed longitudinal bone growth, decreased bone formation, and increased bone resorption. In contrast, the proximal tibia of tail-suspended rats was relatively normal by these histologic criteria. However, a significant reduction trabecular bone volume occurred during 2 weeks of tail suspension, possibly due to a transient inhibition of bone formation. The findings indicate that tail suspension may be a more appropriate model for evaluating the effects of simulated weightlessness on skeletal homeostasis.

  8. Treatment of Anterior Cruciate Ligament Injury in Skeletally Immature Patients

    Directory of Open Access Journals (Sweden)

    Joshua L. Hudgens

    2012-01-01

    Full Text Available The incidence of ACL tears is rising in the pediatric and adolescent populations as these individuals succumb to traumatic and nontraumatic athletic injuries. Management of this condition in the skeletally immature patient poses a challenge and is controversial. Operative reconstruction carries the concern for damage to the physis with resultant limb length inequality and angular joint deformity but provides stability to the knee and allows return of function in most patients. On the other hand, nonoperative treatment has been shown to carry an increased risk of meniscal and articular cartilage damage and is difficult from a compliance standpoint in this demographic. For the majority of skeletally immature patients, operative treatment is recommended as it has shown good clinical and functional results with minimal risk of growth disturbance. This paper aims to address the natural course of ACL injuries in the skeletally immature patient, treatment options with associated complications, and current preventative strategies.

  9. Regulation of Metabolic Signaling in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth

    Regulation of glucose metabolism, despite intense research through decades, is still not clear. Skeletal muscle is highly important for maintaining glucose homeostasis. Regulation of skeletal muscle glucose metabolism is influenced by protein signaling and changes in the activity of metabolic...... enzymes. Skeletal muscle consists of thousands of muscle fibers. These fibers can roughly be classified into type I and type II muscle fibers. The overall aim of this PhD thesis was to investigate the effect of insulin and exercise on human muscle fiber type specific metabolic signaling. The importance of...... biopsies, single muscle fibers were dissected. Muscle fiber type determination was performed and fibers were pooled in groups of type I and II muscle fibers. Muscle fiber pools were investigated for regulation of signaling molecules and enzymes, involved in glucose metabolism. Irrespective of the group of...

  10. Perlecan and synaptophysin changes in denervated skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    Kai Ma; Zhifeng Huang; Jianfeng Ma; Longquan Shao; Huiming Wang; Yanliang Wang

    2012-01-01

    The present study observed sciatic nerve and gastrocnemius muscle changes in denervated rats using morphology methods, and assessed expression of perlecan, an extracellular matrix com-ponent, which is located at the skeletal muscle cell surface as acetylcholine esterase, as well as synaptophysin, a synaptic marker. Results showed degeneration and inflammation following transection of the sciatic nerve. In addition, the sciatic nerve-dominated skeletal muscle degen-erated with mild inflammation, indicating that skeletal muscle atrophy primarily contributed to denervation-induced nutritional disturbances. With prolonged injury time (1-4 weeks post-injury), perlecan expression gradually decreased and reached the lowest level at 4 weeks, but synap-tophysin expression remained unchanged after denervation. Results suggested that perlecan expression was more sensitive to denervation and reflected regional extracellular matrix changes following denervation.

  11. Separation membrane development

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M.W. [Savannah River Technology Center, Aiken, SC (United States)

    1998-08-01

    A ceramic membrane has been developed to separate hydrogen from other gases. The method used is a sol-gel process. A thin layer of dense ceramic material is coated on a coarse ceramic filter substrate. The pore size distribution in the thin layer is controlled by a densification of the coating materials by heat treatment. The membrane has been tested by permeation measurement of the hydrogen and other gases. Selectivity of the membrane has been achieved to separate hydrogen from carbon monoxide. The permeation rate of hydrogen through the ceramic membrane was about 20 times larger than Pd-Ag membrane.

  12. SULFIDE METHOD PLUTONIUM SEPARATION

    Science.gov (United States)

    Duffield, R.B.

    1958-08-12

    A process is described for the recovery of plutonium from neutron irradiated uranium solutions. Such a solution is first treated with a soluble sullide, causing precipitation of the plutoniunn and uraniunn values present, along with those impurities which form insoluble sulfides. The precipitate is then treated with a solution of carbonate ions, which will dissolve the uranium and plutonium present while the fission product sulfides remain unaffected. After separation from the residue, this solution may then be treated by any of the usual methods, such as formation of a lanthanum fluoride precipitate, to effect separation of plutoniunn from uranium.

  13. WET FLUORIDE SEPARATION METHOD

    Science.gov (United States)

    Seaborg, G.T.; Gofman, J.W.; Stoughton, R.W.

    1958-11-25

    The separation of U/sup 233/ from thorium, protactinium, and fission products present in neutron-irradiated thorium is accomplished by dissolving the irradiated materials in aqueous nitric acid, adding either a soluble fluoride, iodate, phosphate, or oxalate to precipltate the thorium, separating the precipltate from the solution, and then precipitating uranlum and protactinium by alkalizing the solution. The uranium and protactinium precipitate is removcd from the solution and dissolved in nitric acid. The uranyl nitrate may then be extracted from the acid solution by means of ether, and the protactinium recovered from the aqueous phase.

  14. Spiral Flow Separator

    Science.gov (United States)

    Robertson, Glen A.

    1993-01-01

    Proposed liquid-separating device relies on centrifugal force in liquid/liquid or liquid/solid mixture in spiral path. Operates in continuous flow at relatively high rates. Spiral tubes joined in sequence, with outlet tubes connected to joints. Cross-sectional areas of successive spiral tubes decreases by cross-sectional areas of outlet tubes. Centrifugal force pushes denser particles or liquids to outer edge of spiral, where removed from flow. Principle exploited to separate solids from wastewater, oil from fresh or salt water, or contaminants from salt water before evaporation. Also used to extract such valuable materials as precious metals from slurries.

  15. Spiral fluid separator

    Science.gov (United States)

    Robertson, Glen A. (Inventor)

    1993-01-01

    A fluid separator for separating particulate matter such as contaminates is provided which includes a series of spiral tubes of progressively decreasing cross sectional area connected in series. Each tube has an outlet on the outer curvature of the spiral. As fluid spirals down a tube, centrifugal force acts to force the heavier particulate matter to the outer wall of the tube, where it exits through the outlet. The remaining, and now cleaner, fluid reaches the next tube, which is smaller in cross sectional area, where the process is repeated. The fluid which comes out the final tube is diminished of particulate matter.

  16. Unity Through Separation

    DEFF Research Database (Denmark)

    Dabelsteen, Hans B.

    analysis, Dabelsteen study Danish secularism as an ideological concept. He finds that the conceptual structure of Danish secularism holds separation-as-principled distance at its core. Institutionally this particularly pertains to the establishment arrangement, and in practice it translates...... into the principle of treating everybody equally (with religious freedom, equality and Danish peoplehood as the most important principles adjacent to secularism). In a study of the historical roots of the separation doctrine and two current policy cases (same-sex marriage and reforms of church governance...

  17. THE USE OF NEW REAGENT KITS FOR DETECTION AND DESCRIPTION OF ADDITIONAL ALLELES

    Directory of Open Access Journals (Sweden)

    M. A. Loginova

    2011-01-01

    Full Text Available During the screening typing of recruited volunteers with Volga Federal District for unrelated hematopoietic stem cell registry on the loci (HLA-A, B, DRB1, DRB345 in sample No 1758 identified a new allele at locus A. The use of basic kit AlleleSEQR HLA-A Sequencing in combination with HARP – A2F98A allowed to determine the genotype of this sample – А*30:01:01, a new allele А*25, В*13, 44, DRB1*03, 09, DRB3*02, DRB4*01. 

  18. Clarifying the Relationship between Average Excesses and Average Effects of Allele Substitutions.

    Science.gov (United States)

    Alvarez-Castro, José M; Yang, Rong-Cai

    2012-01-01

    Fisher's concepts of average effects and average excesses are at the core of the quantitative genetics theory. Their meaning and relationship have regularly been discussed and clarified. Here we develop a generalized set of one locus two-allele orthogonal contrasts for average excesses and average effects, based on the concept of the effective gene content of alleles. Our developments help understand the average excesses of alleles for the biallelic case. We dissect how average excesses relate to the average effects and to the decomposition of the genetic variance. PMID:22509178

  19. Clarifying the relationship between average excesses and average effects of allele substitutions

    Directory of Open Access Journals (Sweden)

    Jose M eÁlvarez-Castro

    2012-03-01

    Full Text Available Fisher’s concepts of average effects and average excesses are at the core of the quantitative genetics theory. Their meaning and relationship have regularly been discussed and clarified. Here we develop a generalized set of one-locus two-allele orthogonal contrasts for average excesses and average effects, based on the concept of the effective gene content of alleles. Our developments help understand the average excesses of alleles for the biallelic case. We dissect how average excesses relate to the average effects and to the decomposition of the genetic variance.

  20. Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange

    DEFF Research Database (Denmark)

    Hmelo, Laura R; Borlee, Bradley R; Almblad, Henrik;

    2015-01-01

    Allelic exchange is an efficient method of bacterial genome engineering. This protocol describes the use of this technique to make gene knockouts and knock-ins, as well as single-nucleotide insertions, deletions and substitutions, in Pseudomonas aeruginosa. Unlike other approaches to allelic...... exchange, this protocol does not require heterologous recombinases to insert or excise selective markers from the target chromosome. Rather, positive and negative selections are enabled solely by suicide vector-encoded functions and host cell proteins. Here, mutant alleles, which are flanked by regions...

  1. Estimation of the frequency of hexosaminidase a variant alleles in the American Jewish population.

    OpenAIRE

    Greenberg, D A; Kaback, M M

    1982-01-01

    There appear to be several alleles of the hexosaminidase A (HEX A) gene that lead to different clinical syndromes. In addition to the infantile-onset Tay-Sachs disease (TSD), there is a juvenile-onset and an adult-onset form, which are also characterized by low HEX A levels. There are also apparently healthy adults with low HEX A activity. Based primarily on data from population screening for TSD carrier status, we estimate the allele frequency of the combined variant alleles for which data a...

  2. Systematic Functional Interrogation of Rare Cancer Variants Identifies Oncogenic Alleles | Office of Cancer Genomics

    Science.gov (United States)

    Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and the function of these alleles remains undefined. We have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. We subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. We identified 12 transforming alleles, including two in genes (PIK3CB, POT1) that have not been shown to be tumorigenic.

  3. Embryonic development of Python sebae - I: Staging criteria and macroscopic skeletal morphogenesis of the head and limbs.

    Science.gov (United States)

    Boughner, Julia C; Buchtová, Marcela; Fu, Katherine; Diewert, Virginia; Hallgrímsson, Benedikt; Richman, Joy M

    2007-01-01

    This study explores the post-ovipositional craniofacial development of the African Rock Python (Python sebae). We first describe a staging system based on external characteristics and next use whole-mount skeletal staining supplemented with Computed tomography (CT) scanning to examine skeletal development. Our results show that python embryos are in early stages of organogenesis at the time of laying, with separate facial prominences and pharyngeal clefts still visible. Limb buds are also visible. By 11 days (stage 3), the chondrocranium is nearly fully formed; however, few intramembranous bones can be detected. One week later (stage 4), many of the intramembranous upper and lower jaw bones are visible but the calvaria are not present. Skeletal elements in the limbs also begin to form. Between stages 4 (day 18) and 7 (day 44), the complete set of intramembranous bones in the jaws and calvaria develops. Hindlimb development does not progress beyond stage 6 (33 days) and remains rudimentary throughout adult life. In contrast to other reptiles, there are two rows of teeth in the upper jaw. The outer tooth row is attached to the maxillary and premaxillary bones, whereas the inner row is attached to the pterygoid and palatine bones. Erupted teeth can be seen in whole-mount stage 10 specimens and are present in an unerupted, mineralized state at stage 7. Micro-CT analysis reveals that all the young membranous bones can be recognized even out of the context of the skull. These data demonstrate intrinsic patterning of the intramembranous bones, even though they form without a cartilaginous template. In addition, intramembranous bone morphology is established prior to muscle function, which can influence bone shape through differential force application. After careful staging, we conclude that python skeletal development occurs slowly enough to observe in good detail the early stages of craniofacial skeletogenesis. Thus, reptilian animal models will offer unique

  4. A novel simple method for determining CYP2D6 gene copy number and identifying allele(s with duplication/multiplication.

    Directory of Open Access Journals (Sweden)

    Taimour Langaee

    Full Text Available Cytochrome P450 2D6 (CYP2D6 gene duplication and multiplication can result in ultrarapid drug metabolism and therapeutic failure or excessive response in patients. Long range polymerase chain reaction (PCR, restriction fragment length polymorphism (RFLP and sequencing are usually used for genotyping CYP2D6 duplication/multiplications and identification, but are labor intensive, time consuming, and costly.We developed a simple allele quantification-based Pyrosequencing genotyping method that facilitates CYP2D6 copy number variation (CNV genotyping while also identifying allele-specific CYP2D6 CNV in heterozygous samples. Most routine assays do not identify the allele containing a CNV. A total of 237 clinical and Coriell DNA samples with different known CYP2D6 gene copy numbers were genotyped for CYP2D6 *2, *3, *4, *6, *10, *17, *41 polymorphisms and CNV determination.The CYP2D6 gene allele quantification/identification were determined simultaneously with CYP2D6*2, *3, *4, *6, *10, *17, *41 genotyping. We determined the exact CYP2D6 gene copy number, identified which allele had the duplication or multiplication, and assigned the correct phenotype and activity score for all samples.Our method can efficiently identify the duplicated CYP2D6 allele in heterozygous samples, determine its copy number in a fraction of time compared to conventional methods and prevent incorrect ultrarapid phenotype calls. It also greatly reduces the cost, effort and time associated with CYP2D6 CNV genotyping.

  5. Differences in the ability to suppress interferon β production between allele A and allele B NS1 proteins from H10 influenza A viruses

    Directory of Open Access Journals (Sweden)

    Zohari Siamak

    2010-12-01

    Full Text Available Abstract Background In our previous study concerning the genetic relationship among H10 avian influenza viruses with different pathogenicity in mink (Mustela vison, we found that these differences were related to amino acid variations in the NS1 protein. In this study, we extend our previous work to further investigate the effect of the NS1 from different gene pools on type I IFN promoter activity, the production of IFN-β, as well as the expression of the IFN-β mRNA in response to poly I:C. Results Using a model system, we first demonstrated that NS1 from A/mink/Sweden/84 (H10N4 (allele A could suppress an interferon-stimulated response element (ISRE reporter system to about 85%. The other NS1 (allele B, from A/chicken/Germany/N/49 (H10N7, was also able to suppress the reporter system, but only to about 20%. The differences in the abilities of the two NS1s from different alleles to suppress the ISRE reporter system were clearly reflected by the protein and mRNA expressions of IFN-β as shown by ELISA and RT-PCR assays. Conclusions These studies reveal that different non-structural protein 1 (NS1 of influenza viruses, one from allele A and another from allele B, show different abilities to suppress the type I interferon β expression. It has been hypothesised that some of the differences in the different abilities of the alleles to suppress ISRE were because of the interactions and inhibitions at later stages from the IFN receptor, such as the JAK/STAT pathway. This might reflect the additional effects of the immune evasion potential of different NS1s.

  6. Ambiguous allele combinations in HLA Class I and Class II sequence-based typing: when precise nucleotide sequencing leads to imprecise allele identification

    Directory of Open Access Journals (Sweden)

    Larsen Paula

    2004-09-01

    Full Text Available Abstract Sequence-based typing (SBT is one of the most comprehensive methods utilized for HLA typing. However, one of the inherent problems with this typing method is the interpretation of ambiguous allele combinations which occur when two or more different allele combinations produce identical sequences. The purpose of this study is to investigate the probability of this occurrence. We performed HLA-A,-B SBT for Exons 2 and 3 on 676 donors. Samples were analyzed with a capillary sequencer. The racial distribution of the donors was as follows: 615-Caucasian, 13-Asian, 23-African American, 17-Hispanic and 8-Unknown. 672 donors were analyzed for HLA-A locus ambiguities and 666 donors were analyzed for HLA-B locus ambiguities. At the HLA-A locus a total of 548 total ambiguous allele combinations were identified (548/1344 = 41%. Most (278/548 = 51% of these ambiguities were due to the fact that Exon 4 analysis was not performed. At the HLA-B locus 322 total ambiguous allele combinations were found (322/1332 = 24%. The HLA-B*07/08/15/27/35/44 antigens, common in Caucasians, produced a large portion of the ambiguities (279/322 = 87%. A large portion of HLA-A and B ambiguous allele combinations can be addressed by utilizing a group-specific primary amplification approach to produce an unambiguous homozygous sequence. Therefore, although the prevalence of ambiguous allele combinations is high, if the resolution of these ambiguities is clinically warranted, methods exist to compensate for this problem.

  7. The HLA-DRB1 allele polymorphisms and nasopharyngeal carcinoma.

    Science.gov (United States)

    Yang, Huimin; Yu, Kaihui; Zhang, Ruoheng; Li, Jiatong; Wei, Xiaomou; Zhang, Yuening; Zhang, Chengdong; Xiao, Feifan; Zhao, Dong; Lin, Xuandong; Wu, Huayu; Yang, Xiaoli

    2016-06-01

    Human leukocyte antigen (HLA)-DRB1 has been reported to influence individual's susceptibility to nasopharyngeal carcinoma (NPC) by many studies in recent years; however, these studies provided controversial results. The meta-analysis was thus conducted here to estimate the relationship between HLA-DRB1 polymorphisms and NPC. After an extensive review of journals from various databases (PubMed, the Web of Science, Embase, China National Knowledge Internet (CNKI), and Wanfang Database), 8 out of 69 case-control studies, including 778 cases and 1148 controls, were extracted. The results showed that 4 of 13 polymorphisms allele are statistically significantly associated with NPC, among them, HLA-DRB1*3, HLA-DRB1*9, and HLA-DRB1*10 may increase the risk of NPC while HLA-DRB1*01 has the opposite effect. The pooled odds ratio and 95 % confidence interval (CI) were 1.702 [95 % CI (1.047, 2.765)], 1.363 [95 % CI (1.029, 1.806)], 1.989 [95 % CI (1.042, 3.799)], and 0.461 [95 % CI (0.315, 0.676)], respectively. In a further ethnicity-based subgroup analysis, HLA-DRB1*08, HLA-DRB1*11, and HLA-DRB1*16 were found to be linked with NPC in Asian, Tunisian, and Caucasian, respectively. In Asian, HLA-DRB1*03, 08, and 10 may elevate the risk whereas HLA-DRB1*09 could lower it. In Tunisian, HLA-DRB1*01 and 11 are the protective factors while HLA-DRB1*03 is the only risk factor. In Caucasian, HLA-DRB1*01 and 03 increase the risk and HLA-DRB1*16 lowers it. The most frequent statistically associated gene is found to be HLA-DRB1*03 which has protective influence on Asian and Tunisian. In conclusion, HLA-DRB1*01, DRB1*03, DRB1*09, and DRB1*10 are related with NPC susceptibility, and the association of HLA-DRB1*08, DRB1*11, and DRB1*16 with NPC risk are significantly different in different ethnicities. PMID:27059731

  8. Angiopoietin-1 enhances skeletal muscle regeneration in mice

    Science.gov (United States)

    Mofarrahi, Mahroo; McClung, Joseph M.; Kontos, Christopher D.; Davis, Elaine C.; Tappuni, Bassman; Moroz, Nicolay; Pickett, Amy E.; Huck, Laurent; Harel, Sharon; Danialou, Gawiyou

    2015-01-01

    Activation of muscle progenitor cell myogenesis and endothelial cell angiogenesis is critical for the recovery of skeletal muscle from injury. Angiopoietin-1 (Ang-1), a ligand of Tie-2 receptors, enhances angiogenesis and skeletal muscle satellite cell survival; however, its role in skeletal muscle regeneration after injury is unknown. We assessed the effects of Ang-1 on fiber regeneration, myogenesis, and angiogenesis in injured skeletal muscle (tibialis anterior, TA) in mice. We also assessed endogenous Ang-1 levels and localization in intact and injured TA muscles. TA fiber injury was triggered by cardiotoxin injection. Endogenous Ang-1 mRNA levels immediately decreased in response to cardiotoxin then increased during the 2 wk. Ang-1 protein was expressed in satellite cells, both in noninjured and recovering TA muscles. Positive Ang-1 staining was present in blood vessels but not in nerve fibers. Four days after the initiation of injury, injection of adenoviral Ang-1 into injured muscles resulted in significant increases in in situ TA muscle contractility, muscle fiber regeneration, and capillary density. In cultured human skeletal myoblasts, recombinant Ang-1 protein increased survival, proliferation, migration, and differentiation into myotubes. The latter effect was associated with significant upregulation of the expression of the myogenic regulatory factors MyoD and Myogenin and certain genes involved in cell cycle regulation. We conclude that Ang-1 strongly enhances skeletal muscle regeneration in response to fiber injury and that this effect is mediated through induction of the myogenesis program in muscle progenitor cells and the angiogenesis program in endothelial cells. PMID:25608750

  9. Pericapillary basement membrane thickening in human skeletal muscles.

    Science.gov (United States)

    Baum, Oliver; Bigler, Marius

    2016-09-01

    The basement membrane (BM) surrounding capillaries in skeletal muscles varies physiologically in thickness according to age, physical fitness, and anatomical site in humans. Furthermore, the pericapillary BM thickness (CBMT) increases pathophysiologically during several common disease states, including peripheral arterial disease and diabetes mellitus. This review on CBM thickening in human skeletal muscles is two pronged. First, it addresses the advantages/disadvantages of grid- and tablet-based measuring and morphometric techniques that are implemented to assess the CBMT on transmission electron micrographs. Second, it deals with the biology of CBM thickening in skeletal muscles, particularly its possible causes, molecular mechanisms, and functional impact. CBM thickening is triggered by several physical factors, including diabetes-associated glycation, hydrostatic pressure, and inflammation. Increased biosynthesis of type IV collagen expression or repetitive cycles in pericyte or endothelial cell degeneration/proliferation appear to be most critical for CBM accumulation. A thickened CBM obviously poses a greater barrier for diffusion, lowers the microvascular elasticity, and impedes transcytosis of inflammatory cells. Our own morphometric data reveal the CBM enlargement to be not accompanied by the pericyte coverage. Owing to an overlap or redundancy in the capillary supply, CBM thickening in skeletal muscles might not be such a devastating occurrence as in organs with endarterial circulation (e.g., kidney and retina). CBM growth in skeletal muscles can be reversed by training or administration of antidiabetic drugs. In conclusion, CBM thickening in skeletal muscles is a microvascular remodeling process by which metabolic, hemodynamic, and inflammatory forces are integrated together and which could play a hitherto underestimated role in etiology/progression of human diseases.

  10. Linkage disequilibrium between HLA-G*0104 and HLA-E*0103 alleles in Tswa Pygmies.

    Science.gov (United States)

    Di Cristofaro, J; Julie, D C; Buhler, S; Frassati, C; Basire, A; Galicher, V; Baier, C; Essautier, A; Regnier, A; Granier, T; Lepfoundzou, A D; Chiaroni, J; Picard, C

    2011-03-01

    Nonclassical human leukocyte antigen (HLA)-G and -E loci are separated by approximately 660 kb on the short arm of chromosome 6. Interestingly, some functional and expression characteristics are relatively identical or associated for both molecules. For example, expression of HLA-E on the cell surface has been linked to preferential binding of nonameric leader peptides derived from the signal sequence of HLA-G. It has been suggested that these two molecules act synergistically in modulating susceptibility to infectious or chronic inflammatory diseases. A possible explanation for these observations is that HLA-E and HLA-G are evolving under analogous selective pressures and have functions that place them under selective regimes differing from classical HLA genes. The purpose of this study was to investigate the consistency of this hypothesis based on the characterization of the molecular polymorphism of these two genes and their linkage disequilibrium (LD) in three populations, i.e. Southeastern French (n = 57), Teke Congolese (n = 84) and Tswa Pygmies (n = 74). Allelic frequencies observed for HLA-G and HLA-E and for 14-bp ins/del polymorphism in the three populations were similar to those observed in the literature for populations from corresponding geographic areas. Only one of the recently described HLA-G polymorphisms (HLA-G*01:07-01:16) was found, i.e. HLA-G*01:15 in one individual from Congo. We showed that two haplotypes in Tswa Pygmies, i.e. HLA-G*01:04-E*01:03:01 and G*01:04-E*01:01, exhibited highly significant positive and negative D' values respectively. Although these LD could have functional implications, it is more likely because of the genetic drift as the two other populations did not display any significant LD.

  11. FREQUENT ALLELIC IMBALANCE AND CYTOGENETIC DELETION ON THE SHORT ARM OF CHROMOSOME 1 IN NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    黄铁军; 黄必军; 张林杰; 梁启万; 方燕

    2004-01-01

    Objective: To construct a fine map of the loss of chromosome lpter-p36.11 region in nasopharyngeal carcinoma (NPC) using PCR-LOH technique. Methods:DNA extracted from separated cancerous cells and their mated noncancerous lymphocytes from 47 cases of NPC biopsies were analyzed by means of PCR-LOH to detect 20loci spanning chromosome lpter-p36.11 region in NPC.Results: In 47 NPC cases, 37 (82.2%) cases showed at least one loci LOH. The highest frequency of less of heterozygosity (LOH) at all 20 loci was found at loci DIS234(50. 0%) on lp36.13 and loci DIS2644 (37.5%) on lp36.22.There was a statistically significant difference betweenDIS234 LOH frequency (60%, 9/15) in early stage and that (50. 0%, 8/16) in advanced stage (P>0.05). Of all 20 STSs (sequence tqgged-site, STS), DIS243 (37.5%) and DIS199(30.2%) showed the highest frequency of MI (microsatellite instability) on lp36.33 and lp36.21, respectively. In addition,several cases showed a contiguous stretch of allelic loss in a different level. Conclusion: Two minimal deletion regions (MDR) on the short arm of chromosome 1 were seated at lp36.13 (DIS234, 2.0 cm) and lp36.22 (DIS436-DIS2644, 6.3cm) respectively, indicating that one or more candidate tumor suppressor gene (TSG) in the two regions may be involved in NPC pathogenesis in an early clinical stage.

  12. Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD

    NARCIS (Netherlands)

    Remels, A.H.; Schrauwen, P.; Broekhuizen, R.; Willems, J.; Kersten, A.H.; Gosker, H.R.; Schols, A.M.

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is a multiorgan systemic disease. The systemic features are skeletal muscle weakness and cachexia, the latter being associated with systemic inflammation. The exact mechanisms underlying skeletal muscle dysfunction in COPD remain obscure. Recent evidence

  13. Understanding Age-Related Changes in Skeletal Muscle Metabolism: Differences Between Females and Males.

    Science.gov (United States)

    Gheller, Brandon J F; Riddle, Emily S; Lem, Melinda R; Thalacker-Mercer, Anna E

    2016-07-17

    Skeletal muscle is the largest metabolic organ system in the human body. As such, metabolic dysfunction occurring in skeletal muscle impacts whole-body nutrient homeostasis. Macronutrient metabolism changes within the skeletal muscle with aging, and these changes are associated in part with age-related skeletal muscle remodeling. Moreover, age-related changes in skeletal muscle metabolism are affected differentially between males and females and are likely driven by changes in sex hormones. Intrinsic and extrinsic factors impact observed age-related changes and sex-related differences in skeletal muscle metabolism. Despite some support for sex-specific differences in skeletal muscle metabolism with aging, more research is necessary to identify underlying differences in mechanisms. Understanding sex-specific aging skeletal muscle will assist with the development of therapies to attenuate adverse metabolic and functional outcomes. PMID:27431365

  14. A study on the change of autophagy in skeletal muscle of patients with chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    黄娟

    2013-01-01

    Objective To study skeletal muscle atrophy and the change of autophagy in skeletal muscle of patients with chronic kidney disease.Methods Mean muscle cross sectional area,mRNA and protein expression of

  15. Allelic frequency distributions of 21 non-combined DNA index system STR loci in a Russian ethnic minority group from Inner Mongolia, China

    Institute of Scientific and Technical Information of China (English)

    Hong-dan WANG; Chun-mei SHEN; Wen-juan LIU; Yu-dang ZHANG; Guang YANG; Jiang-wei YAN; Hai-xia QIN

    2013-01-01

    We studied the allelic frequency distributions and statistical forensic parameters of 21 new short tandem repeat (STR) loci and the amelogenin locus,which are not included in the combined DNA index system (CODIS),in a Russian ethnic minority group from the Inner Mongolia Autonomous Region,China.A total of 114 bloodstain samples from unrelated individuals were extracted and co-amplified with four fluorescence-labeled primers in a multiplex polymerase chain reaction (PCR) system.Using capillary electrophoresis,the PCR products of the 21 STR loci were separated and genotyped.A total of 161 alleles were observed in the Russian ethnic minority group,and corresponding allelic frequencies ranged from 0.0044 to 0.5965.The 21 non-CODIS STR loci of the Russian ethnic minority group were characterized by high genetic diversity and therefore may be useful for elucidating the population's genetic background,for individual identification,and for paternity testing in forensic practice.

  16. Rapid genotyping assays for the 4-base pair deletion of canine MDR1/ABCB1 gene and low frequency of the mutant allele in Border Collie dogs.

    Science.gov (United States)

    Mizukami, Keijiro; Chang, Hye-Sook; Yabuki, Akira; Kawamichi, Takuji; Hossain, Mohammad A; Rahman, Mohammad M; Uddin, Mohammad M; Yamato, Osamu

    2012-01-01

    P-glycoprotein, encoded by the MDR1 or ABCB1 gene, is an integral component of the blood-brain barrier as an efflux pump for xenobiotics crucial in limiting drug uptake into the central nervous system. Dogs homozygous for a 4-base pair deletion of the canine MDR1 gene show altered expression or function of P-glycoprotein, resulting in neurotoxicosis after administration of the substrate drugs. In the present study, the usefulness of microchip electrophoresis for genotyping assays detecting this deletion mutation was evaluated. Mutagenically separated polymerase chain reaction (MS-PCR) and real-time PCR assays were newly developed and evaluated. Furthermore, a genotyping survey was carried out in a population of Border Collies dogs in Japan to determine the allele frequency in this breed. Microchip electrophoresis showed advantages in detection sensitivity and time saving over other modes of electrophoresis. The MS-PCR assay clearly discriminated all genotypes. Real-time PCR assay was most suitable for a large-scale survey due to its high throughput and rapidity. The genotyping survey demonstrated that the carrier and mutant allele frequencies were 0.49% and 0.25%, respectively, suggesting that the mutant allele frequency in Border Collies is markedly low compared to that in the susceptible dog breeds such as rough and smooth Collies. PMID:22362942

  17. A New Cryogenic Air Separation Process with Flash Separator

    OpenAIRE

    Barakat, Taj Alasfia M.; Rabah, Ali A.; Khalel, Zeinab A. M.

    2013-01-01

    A new cryogenic air separation process with flash separator is developed. A flash separator is added to the conventional double-column cryogenic air separation process. The flash separator is used to replace the turbine required to recover a portion of the energy in the double-column air separation process. The flash separator served dual purposes of throttling and separation. Both the conventional and the new processes are simulated using Aspen Plus version 11.1 the model air flow rate and c...

  18. New Mechanics of Generic Musculo-Skeletal Injury

    OpenAIRE

    Ivancevic, Vladimir G.

    2008-01-01

    Prediction and prevention of musculo-skeletal injuries is an important aspect of preventive health science. Using as an example a human knee joint, this paper proposes a new coupled-loading-rate hypothesis, which states that a generic cause of any musculo-skeletal injury is a Euclidean jolt, or SE(3)-jolt, an impulsive loading that hits a joint in several coupled degrees-of-freedom simultaneously. Informally, it is a rate-of-change of joint acceleration in all 6-degrees-of-freedom simultaneou...

  19. Long-term skeletal findings in Menkes disease

    Energy Technology Data Exchange (ETDEWEB)

    Amador, Eva [Son Dureta Children' s Hospital, Department of Paediatric Radiology, Palma de Mallorca (Spain); Domene, Ruth; Fuentes, Cristian; Carreno, Juan-Carlos; Enriquez, Goya [Vall d' Hebron Children' s Hospital, Department of Paediatric Radiology, Barcelona (Spain)

    2010-08-15

    Skeletal findings in infants with Menkes disease, the most characteristic of which are metaphyseal spurs, long-bone fractures and wormian bones, have been widely reported. However, the changes in skeletal features over time are not well known. The long-term findings differ completely from those initially observed and consist of undertubulation and metaphyseal flaring, similar to the findings seen in some types of bone dysplasia. The initial and long-term radiological features in an 8-year-old boy with Menkes disease are illustrated. (orig.)

  20. Toll-like receptor 4 modulates skeletal muscle substrate metabolism

    OpenAIRE

    Frisard, Madlyn I.; McMillan, Ryan P.; Marchand, Julie; Wahlberg, Kristin A.; Wu, Yaru; Voelker, Kevin A.; Heilbronn, Leonie; Haynie, Kimberly; Muoio, Brendan; Li, Liwu; Hulver, Matthew W.

    2010-01-01

    Toll-like receptor 4 (TLR4), a protein integral to innate immunity, is elevated in skeletal muscle of obese and type 2 diabetic humans and has been implicated in the development of lipid-induced insulin resistance. The purpose of this study was to examine the role of TLR4 as a modulator of basal (non-insulin-stimulated) substrate metabolism in skeletal muscle with the hypothesis that its activation would result in reduced fatty acid oxidation and increased partitioning of fatty acids toward n...