Sample records for beta major deletion

  1. Bacillus subtilis generates a major specific deletion in pAM beta 1.


    van der Lelie, D; Venema, G


    pAM beta 1, a 26.5-kilobase plasmid originally isolated from Streptococcus faecalis, was conjugally transferred from Streptococcus lactis to Bacillus subtilis. No conjugal transfer of pAM beta 1 from B. subtilis to S. lactis was observed. In addition, pAM beta 1 which had been reintroduced in S. lactis after cycling through B. subtilis had lost its conjugal transferability to Streptococcus cremoris, although under the same conditions noncycled pAM beta 1 was transferred at high efficiency. Re...

  2. CCAAT/enhancer binding protein {beta} deletion increases mitochondrial function and protects mice from LXR-induced hepatic steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, Shaikh M., E-mail: [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Choudhury, Mahua; Janssen, Rachel C.; Baquero, Karalee C. [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Miyazaki, Makoto [Division of Renal Diseases and Hypertension, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Friedman, Jacob E. [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States)


    Highlights: Black-Right-Pointing-Pointer LXR agonist activation increases liver TG accumulation by increasing lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta}{sup -/-} mouse prevents LXR activation-mediated induction of hepatic lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta} deletion increases mitochondrial transport chain function. Black-Right-Pointing-Pointer Beneficial effects of LXR activation on liver cholesterol metabolism did not change. Black-Right-Pointing-Pointer C/EBP{beta} inhibition might have important therapeutic potential. -- Abstract: Drugs designed specifically to activate liver X receptors (LXRs) have beneficial effects on lowering cholesterol metabolism and inflammation but unfortunately lead to severe hepatic steatosis. The transcription factor CCAAT/enhancer binding protein beta (C/EBP{beta}) is an important regulator of liver gene expression but little is known about its involvement in LXR-based steatosis and cholesterol metabolism. The present study investigated the role of C/EBP{beta} expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBP{beta} deletion in mice prevented LXR agonist-mediated induction of lipogenic gene expression in liver in conjunction with significant reduction of liver TG accumulation. Surprisingly, C/EBP{beta}{sup -/-} mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBP{beta}{sup -/-} mice increased the expression of liver ATP-binding cassette transporter ABCG1, a gene implicated in cholesterol efflux and reducing blood levels of total and LDL-cholesterol. Together, these findings establish a central role for C/EBP{beta} in the LXR-mediated steatosis and mitochondrial function, without impairing the influence of LXR activation on lowering LDL and increasing HDL-cholesterol. Inactivation of C/EBP{beta} might therefore be an important therapeutic strategy to prevent LXR

  3. Deletion of glutamate dehydrogenase in beta-cells abolishes part of the insulin secretory response not required for glucose homeostasis

    DEFF Research Database (Denmark)

    Carobbio, Stefania; Frigerio, Francesca; Rubi, Blanca


    Insulin exocytosis is regulated in pancreatic ss-cells by a cascade of intracellular signals translating glucose levels into corresponding secretory responses. The mitochondrial enzyme glutamate dehydrogenase (GDH) is regarded as a major player in this process, although its abrogation has not been...... tested yet in animal models. Here, we generated transgenic mice, named betaGlud1(-/-), with ss-cell-specific GDH deletion. Our results show that GDH plays an essential role in the full development of the insulin secretory response. In situ pancreatic perfusion revealed that glucose-stimulated insulin...... secretion was reduced by 37% in betaGlud1(-/-). Furthermore, isolated islets with either constitutive or acute adenovirus-mediated knock-out of GDH showed a 49 and 38% reduction in glucose-induced insulin release, respectively. Adenovirus-mediated re-expression of GDH in betaGlud1(-/-) islets fully restored...

  4. Portal vein thrombosis after splenectomy for beta-thalassemia major

    International Nuclear Information System (INIS)

    Al-Hawsawi, Zakaria M.; Tarawah, Ahmed M.; Hassan, Ruhul Amin A.; Haouimi, Ammar S.


    Portal vein thrombosis is a recognized complication after splenectomy for beta-thalassemia major due to the chronic hypercoagulable state which has been recognized to exist in childhood thalassemia and contribute to thromboembolic events. We reporting one patient with beta-thalassemia major developed portal vein thrombosis following splenectomy. (author)

  5. Scintigraphic evaluation of bone involvement in beta thalassemia major

    International Nuclear Information System (INIS)

    Armijo, Soledad; Hidalgo, Pablo


    In this article, the authors describe a 19 year old man with beta-thalassemia major and back pain, who was studied with a Tc99m Metilendiphosphonate (Tc99m MDP) bone scan. This case shows many of the complications of beta-thalassemia major in the skeletal system. Also we can see some indirect signs of endocrinopathies associated (Au)

  6. Anaesthesia for a patient with beta thalassaemia major ...

    African Journals Online (AJOL)

    Presented here is a case report of a 32-year-old gentleman with beta thalassaemia major presenting for elective laparoscopic cholecystectomy and splenectomy, followed by a discussion of the literature. Keywords: anaemia, anaesthesia, beta thalassaemia, iron overload, laparoscopic cholecystectomy, splenectomy ...

  7. Deletion mutant defines DQ beta variants with DR4 positive DQw3 positive haplotypes

    International Nuclear Information System (INIS)

    Nepom, B.S.; Kim, S.J.; Nepom, G.T.


    We describe the production of an HLA deletion mutation by radiation mutagenesis of a DR4- and DQw3-homozygous, Dw4- and Dw14-heterozygous cell line designed to analyze polymorphisms associated with DR4 and DQw3. Southern blot analysis confirms a deletion of class I and class II genes on one haplotype. Variation in DQ beta alleles associated with DQw3 was previously described by characteristic RFLP patterns for a DQ beta bene. One pattern, which correlated precisely with A-10-83 monoclonal antibody reactivity (TA10), defined an allele which we call DQ''3.1''. The mutant cell line has lost the polymorphic bands on Southern blots corresponding to the DQ''3.1'' allele, while the intact Dw14 haplotype retains the alternate allele at DQ beta which is DQw-3 positive. TA10-negative. These data demonstrate the segregation of two DQw3 positive DQ beta allelic variants, both associated with DR4, which can be distinguished on the basis of both RFLP and monoclonal antibody reactivity

  8. Hemolytic disease of the newborn caused by a new deletion of the entire beta-globin cluster.


    Pirastu, M; Kan, Y W; Lin, C C; Baine, R M; Holbrook, C T


    We describe a new type of gamma delta beta-thalassemia in four generations of a family of Scotch-Irish descent. The proposita presented with hemolytic disease of the newborn, which was characterized by a microcytic anemia. Initial restriction endonuclease analysis of the DNA showed no grossly abnormal patterns, but studies of polymorphic restriction sites and gene dosage revealed an extensive deletion that removed all the beta- and beta-like globin genes from the affected chromosome. In situ ...

  9. Lack of Association between Dopamine Beta-Hydroxylase (DBH 19-bp Insertion/Deletion Polymorphism and Risk of Schizophrenia

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    Mansour shakiba


    Full Text Available Objective: Interaction between genetic and environmental factors is considered as major factors in Schizophrenia (SCZ. It has been shown that dopaminergic and noradrenergic neurotransmission dysfunction play an essential role in the SCZ pathogenesis.This study aimed to find the impact of functional 19-bp insertion/deletion (ins/del polymorphism in dopamine beta-hydroxylase (DBH gene on SCZ risk in a sample of Iranian population.Method: This case-control study was conducted on 109 SCZ patients and 116 matched healthy subjects. Genomic DNA samples were extracted from peripheral blood cells using salting out method. Genotyping of 19-bp ins/del DBH polymorphism was done using Polymerase Chain Reaction (PCR method.Results: Neither the overall chi-square comparison of cases and controls (

  10. Characterization of a large deletion in the {beta}-globin gene cluster in a newborn with hemoglobin FE

    Energy Technology Data Exchange (ETDEWEB)

    Louie, E.; Dietz, L.; Shafer, F. [Children`s Hosptial, Oakland, CA (United States)] [and others


    A sample on a newborn with hemoglobin FE screen results was obtained to investigate whether E/E or B/{beta}{degrees} thalassemia was present using polymerase chain reaction (PCR) methodology. The newborn appeared homozygous for the hemoglobin E mutation in our initial study, but the parents` genotypes did not support this diagnosis. The father is homozygous for the absence of the hemoglobin E mutation (non E/non E) and the mother is heterozygous (E/non E) for this mutation. The limitation of PCR analysis is an assumption that the amplification of the two {beta}-globin alleles is equivalent. A large deletion on one {beta}-globin gene, which would produce E/{beta}{degrees} thalassemia, would be missed if it included part or the entire region subjected to amplification. The family results were consistent with either non-paternity, sample mix-up or such a deletion of the {beta}-globin gene in the father and child. To rule out the possibility of non-paternity, two polymorphic loci (HLA on chromosome 6 and a VNTR system of chromosome 17) that are outside of the {beta}-globin gene were analyzed and show that inheritance is consistent and the likelihood of a sample mix-up is then reduced. We therefore believe there is a gene deletion in this family. At the present time, analyses of the RFLPs that are 5{prime} of the {beta}-globin gene cluster show that the polymorphisms most distal from the 5{prime} {beta}-globin gene are not being inherited as expected. These results support our interpretation that a deletion exists in the father and was inherited by the child. The father`s clinical picture of possible HPFH (the father has 12% hemoglobin F) also supports the interpretation of a deletion in this family. Deletions of the {beta}-globin gene within this ethnic group are rare. Currently, Southern blots on the family are being probed to determine the extent of the putative deletion.

  11. A comparison of heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major. (United States)

    Amoozgar, Hamid; Zeighami, Samaneh; Haghpanah, Sezaneh; Karimi, Mehran


    The goal of this study was to compare heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major. In this cross-sectional study, 60 patients with beta thalassemia major and 60 patients with beta thalassemia intermedia who had clinically no symptoms of arrhythmia and clinically normal heart function were evaluated using 24-hour ambulatory electrocardiogram monitoring and echocardiography. For data analysis SPSS ver.20 software was used. A P-value of less than 0.05 was considered statistically significant. The mean age of the beta thalassemia intermedia patients was 24.18 ± 7.9 years and the mean age in beta thalassemia major was 24.38 ± 7.7 years (P>0.05). Premature atrial contractions (PACs) were observed in 14 (23.3%) patients with beta thalassemia intermedia and in 22 (36.6%) beta thalassemia major patients. Premature ventricular contractions (PVCs) were detected in 8 (13.3%) patients in the beta thalassemia intermediate group and 16 (26.6) patients in the beta thalassemia major group, respectively. The left ventricular diastolic dimension, end-diastolic volume, and stroke volume were significantly higher in beta thalassemia intermedia group (Pintermedia group. Both atrial and ventricular arrhythmias were more common in the beta thalassemia major group. Higher end-diastolic volume and stroke volume were detected in the beta thalassemia intermedia group. Pulmonary acceleration time was lower in the beta thalassemia intermedia group, which can be an indicator of higher pulmonary pressure.

  12. Attenuated Response to Methamphetamine Sensitization and Deficits in Motor Learning and Memory after Selective Deletion of [beta]-Catenin in Dopamine Neurons (United States)

    Diaz-Ruiz, Oscar; Zhang, YaJun; Shan, Lufei; Malik, Nasir; Hoffman, Alexander F.; Ladenheim, Bruce; Cadet, Jean Lud; Lupica, Carl R.; Tagliaferro, Adriana; Brusco, Alicia; Backman, Cristina M.


    In the present study, we analyzed mice with a targeted deletion of [beta]-catenin in DA neurons (DA-[beta]cat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-[beta]cat KO mice showed significant…

  13. Levels of Beta-2 Microglobulin and Cystatin C in Beta Thalassemia Major Patients

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    Ayse Kacar


    Full Text Available Aim: Thalassemia is accepted to be the most common genetic disease in the world. This study was performed to establish whether there was a glomerular renal damage, which was usually a less mentioned subject in patients with Beta Thalassemia Major, and to compare urea, creatinine and creatinine clearance with early indicators of kidney damage as Cystatin-C and %u03B2-2 microglobulin as on determining the glomerular damage. Material and Method: This study was prospectively performed in patients, who were regularly followed in the children hematology outpatient clinic with a diagnosis of Beta Thalassemia Major. Results: There was no statistically significant difference between urea and levels of creatinine clearance and Cystatin-C. There was a statistically negative relationship between creatinine and creatinine clearance at an advanced level as 53.7% (p: 0.002, p

  14. Deletion of a region that is a candidate for the difference between the deletion forms of hereditary persistence of fetal hemoglobin and deltabeta-thalassemia affects beta- but not gamma-globin gene expression.

    NARCIS (Netherlands)

    R. Calzolari (Roberta); T. McMorrow (Tara); N. Yannoutsos (Nikos); A. Langeveld (An); F.G. Grosveld (Frank)


    textabstractThe analysis of a number of cases of beta-globin thalassemia and hereditary persistence of fetal hemoglobin (HPFH) due to large deletions in the beta-globin locus has led to the identification of several DNA elements that have been implicated in the switch

  15. Current and future alternative therapies for beta-thalassemia major

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    Edouard de Dreuzy


    Full Text Available Beta-thalassemia is a group of frequent genetic disorders resulting in the synthesis of little or no β-globin chains. Novel approaches are being developed to correct the resulting α/β-globin chain imbalance, in an effort to move beyond the palliative management of this disease and the complications of its treatment (e.g. life-long red blood cell transfusion, iron chelation, splenectomy, which impose high costs on healthcare systems. Three approaches are envisaged: fetal globin gene reactivation by pharmacological compounds injected into patients throughout their lives, allogeneic hematopoietic stem cell transplantation (HSCT, and gene therapy. HSCT is currently the only treatment shown to provide an effective, definitive cure for β-thalassemia. However, this procedure remains risky and histocompatible donors are identified for only a small fraction of patients. New pharmacological compounds are being tested, but none has yet made it into common clinical practice for the treatment of beta-thalassemia major. Gene therapy is in the experimental phase. It is emerging as a powerful approach without the immunological complications of HSCT, but with other possible drawbacks. Rapid progress is being made in this field, and long-term efficacy and safety studies are underway.

  16. Diagnosis of Beta-thalassaemia major in previously transfused patients

    International Nuclear Information System (INIS)

    Ahmed, S.; Rehman, Z.; Karamat, K.A.


    Objective: The study was conducted to evaluate the effects of blood transfusion(s) on the haematological picture of beta-thalassaemia major. Results: Out of the 280 patients 109 (39%) had received one or more blood transfusions (cases). The remaining 171 patients who did not receive any transfusion served as controls. The mean MCV, MCH and Hb-F in cases were significantly higher than in the controls (p 4 transfusions (17%) (p=0.016). In the occasionally transfused patients Hb-F level was directly related to the time since last transfusion. In 44/109 (40%) transfused patients (Hb-F>30%) the diagnosis of thalassaemia was not difficult. In 54/109 (50%) patients (Hb-:5-30%) the diagnosis was aided by parent's study, while PCR for thalassaemia mutation was required in 11/109 (10%) patients (Hb-F <5%). Conclusion: In most transfused patients of thalassaemia major MCV and MCH were significantly higher while Hb-F was lower than in the un-transfused patients. There was a linear correlation between Hb-F level and time since last transfusion in the occasionally transfused patients. However, the reduction in Hb-F level was more marked and sustained in multipally transfused patients. Parent's study and PCR are useful aids in establishing the correct diagnosis in these patients. (author)

  17. Deletion of Lytic Transglycosylases Increases Beta-Lactam Resistance in Shewanella oneidensis (United States)

    Yin, Jianhua; Sun, Yiyang; Sun, Yijuan; Yu, Zhiliang; Qiu, Juanping; Gao, Haichun


    Production of chromosome-encoded β-lactamases confers resistance to β-lactams in many Gram-negative bacteria. Some inducible β-lactamases, especially the class C β-lactamase AmpC in Enterobacteriaceae, share a common regulatory mechanism, the ampR-ampC paradigm. Induction of ampC is intimately linked to peptidoglycan recycling, and the LysR-type transcriptional regulator AmpR plays a central role in the process. However, our previous studies have demonstrated that the expression of class D β-lactamase gene blaA in Shewanella oneidensis is distinct from the established paradigm since an AmpR homolog is absent and major peptidoglycan recycling enzymes play opposite roles in β-lactamase expression. Given that lytic transglycosylases (LTs), a class of peptidoglycan hydrolases cleaving the β-1,4 glycosidic linkage in glycan strands of peptidoglycan, can disturb peptidoglycan recycling, and thus may affect induction of blaA. In this study, we investigated impacts of such enzymes on susceptibility to β-lactams. Deletion of three LTs (SltY, MltB and MltB2) increased β-lactam resistance, while four other LTs (MltD, MltD2, MltF, and Slt2) seemed dispensable to β-lactam resistance. The double LT mutants ΔmltBΔmltB2 and ΔsltYΔmltB2 had β-lactam resistance stronger than any of the single mutants. Deletion of ampG (encoding permease AmpG) and mrcA (encoding penicillin binding protein 1a, PBP1a) from both double LT mutants further increased the resistance to β-lactams. Notably, all increased β-lactam resistance phenotypes were in accordance with enhanced blaA expression. Although significant, the increase in β-lactamase activity after inactivating LTs is much lower than that produced by PBP1a inactivation. Our data implicate that LTs play important roles in blaA expression in S. oneidensis. PMID:29403465

  18. Evaluation of pulmonary function in beta-thalassemia major patients

    International Nuclear Information System (INIS)

    Eidani, I.; Keikhaei, B.; Rahim, F.; Bagheri, A.


    Objective: To describe and quantify the functional change of the lung in patients with beta-thalassemia major (TM) and determine the correlation between pulmonary function test (PFT) results with hemoglobin, ferritin and age changes. Methodology: Pulmonary function tests were performed on 60 transfusion-dependent patients with TM, ranging in age from 10 to 45 years. Percent-predicted values for forced expiratory volume in one second (FEV1), and forced expiratory flows (FEF) 25-75% were significantly reduced, whereas forced expiratory vital capacity (FVC) and FEV1/FVC were closed to normal limits, indicating a restrictive disease. All factors including; FVC, FEV1, and FEV1/FVC, FEF 25-75% were negatively correlated with age and ferritin levels. In contrast, all factors including; FVC, FEV1, and FEV1/FVC, FEF 25-75% were positively correlated with hemoglobin (Hb). We performed linear regression analysis to study the simultaneous influence of the presence of age, ferritin, and Hb on obstructive PFT indexes. Results: Pulmonary function test results were normal in only 32 (53.3%) of 60 patients and the rest 28 cases (46.7%) showed abnormal pulmonary function. FEV1 and FEF 25% - 75% have significant negative correlation with age (r = - 0.64 p(r) = 0.003 and r = - 0.58 p(r) = 0.02 respectively), also have significant positive correlation with Hb (r = 0.31 p(r) = 0.015 and r = 0.33 p(r) = 0.01 respectively), and only FEF 25% - 75% has significant negative correlation with ferritin (r -0.26 p(r) = 0.04). Conclusion: The present study has shown that restrictive disease and reduced lung diffusing capacity are the predominant abnormalities of pulmonary function patients with TM. The low hemoglobin concentration and a fall in the diffusing capacity of the alveola - capillary membrane, together with the dependence of the reduced pulmonary diffusing capacity on age and serum ferritin levels, as well as of the entity of restrictive disease on age, suggests that pulmonary

  19. Anaesthesia for a patient with beta thalassaemia major

    African Journals Online (AJOL)

    Creative Commons License [CC BY-NC-ND 4.0] ... monitoring and management instituted. The first arterial blood ... thalassaemia is a defect of the beta globin chains of the ... Decreased supply due to anaemia, chronic infections and frequent ...

  20. Expression of deleted, atoxic atypical recombinant beta2 toxin in a baculovirus system and production of polyclonal and monoclonal antibodies. (United States)

    Serroni, Anna; Magistrali, Chiara Francesca; Pezzotti, Giovanni; Bano, Luca; Pellegrini, Martina; Severi, Giulio; Di Pancrazio, Chiara; Luciani, Mirella; Tittarelli, Manuela; Tofani, Silvia; De Giuseppe, Antonio


    Clostridium perfringens is an important animal and human pathogen that can produce more than 16 different major and minor toxins. The beta-2 minor toxin (CPB2), comprising atypical and consensus variants, appears to be involved in both human and animal enterotoxaemia syndrome. The exact role of CPB2 in pathogenesis is poorly investigated, and its mechanism of action at the molecular level is still unknown because of the lack of specific reagents such as monoclonal antibodies against the CPB2 protein and/or the availability of a highly purified antigen. Previous studies have reported that purified wild-type or recombinant CPB2 toxin, expressed in a heterologous system, presented cytotoxic effects on human intestinal cell lines. Undoubtedly, for this reason, to date, these purified proteins have not yet been used for the production of monoclonal antibodies (MAbs). Recently, monoclonal antibodies against CPB2 were generated using peptides designed on predicted antigenic epitopes of this toxin. In this paper we report, for the first time, the expression in a baculovirus system of a deleted recombinant C-terminal 6xHis-tagged atypical CPB2 toxin (rCPB2 Δ1-25 -His 6 ) lacking the 25 amino acids (aa) of the N-terminal putative signal sequence. A high level of purified recombinant rCPB2 Δ1-25 -His 6 was obtained after purification by Ni 2+ affinity chromatography. The purified product showed no in vitro and in vivo toxicity. Polyclonal antibodies and twenty hybridoma-secreting Mabs were generated using purified rCPB2 Δ1-25 -His 6 . Finally, the reactivity and specificity of the new antibodies were tested against both recombinant and wild-type CPB2 toxins. The high-throughput of purified atoxic recombinant CPB2 produced in insect cells, allowed to obtain monoclonal and polyclonal antibodies. The availability of these molecules could contribute to develop immunoenzymatic methods and/or to perform studies about the biological activity of CPB2 toxin.

  1. Deletion of hepatocyte nuclear factor-1-beta in an infant with prune belly syndrome. (United States)

    Haeri, Sina; Devers, Patricia L; Kaiser-Rogers, Kathleen A; Moylan, Vincent J; Torchia, Beth S; Horton, Amanda L; Wolfe, Honor M; Aylsworth, Arthur S


    Prune belly syndrome is a rare congenital disorder characterized by deficiency of abdominal wall muscles, cryptorchidism, and urinary tract anomalies. We have had the opportunity to study a baby with prune belly syndrome associated with an apparently de novo 1.3-megabase interstitial 17q12 microdeletion that includes the hepatocyte nuclear factor-1-beta gene at 17q12. One previous patient, an adult, has been reported with prune belly syndrome and a hepatocyte nuclear factor-1-beta microdeletion. Hepatocyte nuclear factor-1-beta is a widely expressed transcription factor that regulates tissue-specific gene expression and is expressed in numerous tissues including mesonephric duct derivatives, the renal tubule of the metanephros, and the developing prostate of the mouse. Mutations in hepatocyte nuclear factor-1-beta cause the "renal cysts and diabetes syndrome," isolated renal cystic dysplasia, and a variety of other malformations. Based on its expression pattern and the observation of two affected cases, we propose that haploinsufficiency of hepatocyte nuclear factor-1-beta may be causally related to the production of the prune belly syndrome phenotype through a mechanism of prostatic and ureteral hypoplasia that results in severe obstructive uropathy with urinary tract and abdominal distension. Copyright Thieme Medical Publishers.

  2. Astrocytic beta 2 Adrenergic Receptor Gene Deletion Affects Memory in Aged Mice

    NARCIS (Netherlands)

    Jensen, Cathy Joanna; Demol, Frauke; Bauwens, Romy; Kooijman, Ron; Massie, Ann; Villers, Agnes; Ris, Laurence; De Keyser, Jacques


    In vitro and in vivo studies suggest that the astrocytic adrenergic signalling enhances glycogenolysis which provides energy to be transported to nearby cells and in the form of lactate. This energy source is important for motor and cognitive functioning. While it is suspected that the beta

  3. Deletion of Nhlh2 results in a defective torpor response and reduced Beta adrenergic receptor expression in adipose tissue.

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    Umesh D Wankhade


    Full Text Available Mice with a targeted deletion of the basic helix-loop-helix transcription factor, Nescient Helix-Loop-Helix 2 (Nhlh2, display adult-onset obesity with significant increases in their fat depots, abnormal responses to cold exposure, and reduced spontaneous physical activity levels. These phenotypes, accompanied by the hypothalamic expression of Nhlh2, make the Nhlh2 knockout (N2KO mouse a useful model to study the role of central nervous system (CNS control on peripheral tissue such as adipose tissue.Differences in body temperature and serum analysis of leptin were performed in fasted and ad lib fed wild-type (WT and N2KO mice. Histological analysis of white (WAT and brown adipose tissue (BAT was performed. Gene and protein level expression of inflammatory and metabolic markers were compared between the two genotypes.We report significant differences in serum leptin levels and body temperature in N2KO mice compared with WT mice exposed to a 24-hour fast, suggestive of a defect in both white (WAT and brown adipose tissue (BAT function. As compared to WT mice, N2KO mice showed increased serum IL-6 protein and WAT IL-6 mRNA levels. This was accompanied by slight elevations of mRNA for several macrophage markers, including expression of macrophage specific protein F4/80 in adipose, suggestive of macrophage infiltration of WAT in the mutant animals. The mRNAs for beta3-adrenergic receptors (beta3-AR, beta2-AR and uncoupling proteins were significantly reduced in WAT and BAT from N2KO mice compared with WT mice.These studies implicate Nhlh2 in the central control of WAT and BAT function, with lack of Nhlh2 leading to adipose inflammation and altered gene expression, impaired leptin response to fasting, all suggestive of a deficient torpor response in mutant animals.

  4. beta-thalassaemia major hos børn og unge i Danmark

    DEFF Research Database (Denmark)

    Jung, Anne; Main, Katharina Maria; Scheibel, Elma


    INTRODUCTION: Beta-thalassemia major occurs with increasing frequency among Danish children as a result of immigration. The aim of the study was to estimate the occurrence of beta-thalassemia major in Denmark, analyse the treatment and organ functions, and identify areas for an improved treatment...... strategy. MATERIAL AND METHODS: During 1998-99 all Danish pediatric departments were contacted for identification of children aged 0-18 years with beta-thalassemia major. Blood transfusions and chelation therapy were registered, and for Eastern Denmark clinical, endocrine, cardiac, and serologic parameters...... were performed. RESULTS: Twenty-six children had beta-thalassemia major. Out of these, 20 received blood transfusions, and 17 patients were chelated. Eight patients were not chelated owing to previous bone marrow transplantation, treatment with hydroxyurea or ferritin

  5. Beta-thalassaemia major hos børn og unge i Danmark

    DEFF Research Database (Denmark)

    Jung, A.; Main, K.M.; Scheibel, E.


    INTRODUCTION: Beta-thalassemia major occurs with increasing frequency among Danish children as a result of immigration. The aim of the study was to estimate the occurrence of beta-thalassemia major in Denmark, analyse the treatment and organ functions, and identify areas for an improved treatment...... strategy. MATERIAL AND METHODS: During 1998-99 all Danish pediatric departments were contacted for identification of children aged 0-18 years with beta-thalassemia major. Blood transfusions and chelation therapy were registered, and for Eastern Denmark clinical, endocrine, cardiac, and serologic parameters...... were performed. RESULTS: Twenty-six children had beta-thalassemia major. Out of these, 20 received blood transfusions, and 17 patients were chelated. Eight patients were not chelated owing to previous bone marrow transplantation, treatment with hydroxyurea or ferritin

  6. Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle (United States)

    Sakhnini, Lama


    In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.

  7. Nitroblue tetrazolium test in patients with beta-thalassemia major

    International Nuclear Information System (INIS)

    Ghaffari, J.; Vahidshahi, K.; Kosaryan, M.; Karami, H.; Mahdavi, M.; Parvinnejad, N.


    Objective to assess the neutrophil function in thalassemia major (TM)patients and compare it with the control group and to recognize its relevantfactors. This was a retrospective cohort study, which was carried out fromOctober 2007 to February 2008 in the Thalassemia research Center in Boo AliSina Hospital in Sari, Mazandaran, North of Iran. The study populationconsisted of TM patients in Boo Ali Sina Teaching Hospital. The method ofsampling in the case group was systematic and it was target based in thecontrol group. The sample size determined was based on previous studies.Thalassemia major was diagnosed based on hemoglobin electrophoresis (casegroup). The control group was their brothers and sisters, who had +-5 yearsof age difference and were of the same gender as the patients. Datacollection was based on interview, investigating demographic characteristicsand also obtaining medical information from medical records of the patients.The neutrophil function was by performing nitroblue tetrazolium (NBT)reduction test. The test was carried out on both groups and the data wereanalyzed by software using SPSS version 13.0. In this study, 39 patients and39 healthy controls were compared. The average age of the patients was21.6+-5.3 years and it was 22.4+-5.1 years in healthy controls (p=0.7). Therewas a significant correlation between the test's results and the patients age(p=0.008). The rate of impaired NBT results in the patients was 36%, while itwas 10% in controls, which were significantly different. The neutrophilactivity based on NBT test was 89.9+-11.6% in the case group and 93.7+-2.51%in the control group (p=0.025). This study indicates that neutrophil activityin thalassemia patients was significantly lower, compared to the normalcontrol group, especially in young patients. Based on the results, evaluationof neutrophil function and pyogenic infections in TM patients seemsnecessary. (author)

  8. Prevalence of major depressive disorder in patients receiving beta-blocker therapy versus other medications. (United States)

    Carney, R M; Rich, M W; teVelde, A; Saini, J; Clark, K; Freedland, K E


    Depression is believed to be a common side effect in patients receiving beta-blocker therapy. However, diagnoses of depression defined by current diagnostic criteria may not be more common in patients receiving beta-blockers than in patients with the same medical disorder receiving other medications. Seventy-seven patients undergoing elective cardiac catheterization for evaluation of chest pain received a semi-structured diagnostic psychiatric interview. Twenty-one percent of the patients receiving beta-blockers and 33 percent of the patients receiving medications other than beta-blockers met the current American Psychiatric Association criteria for major depressive disorder (DSM-III) (p = NS). The mean heart rate and state anxiety scores for patients taking beta-blockers were significantly lower than those measured in patients taking medications other than beta-blockers. No other medical or demographic differences were observed between the two groups. Despite the methodologic limitations of the study, there does not appear to be a difference in the point prevalence of depression between patients receiving beta-blockers and those receiving other medications.

  9. Human parvovirus B19 in patients with beta thalassemia major from Tehran, Iran. (United States)

    Arabzadeh, Seyed Ali Mohammad; Alizadeh, Farideh; Tavakoli, Ahmad; Mollaei, Hamidreza; Bokharaei-Salim, Farah; Karimi, Gharib; Farahmand, Mohammad; Mortazavi, Helya Sadat; Monavari, Seyed Hamidreza


    Due to the tropism of human parvovirus B19 to erythroid progenitor cells, infection in patients with an underlying hemolytic disorder such as beta-thalassemia major leads to suppression of erythrocyte formation, referred to as transient aplasia crisis (TAC), which may be life-threatening. We investigated the prevalence of parvovirus B19 among patients with beta thalassemia major attending the Zafar Adult Thalassemia Clinic in Tehran, Iran. This cross-sectional study was performed to determine the presence of parvovirus B19 DNA in blood samples and parvovirus B19 genotypes in plasma samples of patients with thalassemia major. The population consisted of 150 patients with beta-thalassemia major who attended the Zafar clinic in Tehran. Specimens were studied using a real-time polymerase chain reaction assay. The prevalence of parvovirus B19 in our study population was 4%. Of 150 patients with thalassemia, six (4%) were positive for B19 DNA. There was no significant correlation between blood transfusion frequency and B19 DNA positivity. Finally, phylogenetic analysis of human parvovirus B19 revealed genotype I in these six patients. In this study, acute B19 infections were detected in patients with beta thalassemia major. Screening of such high-risk groups can considerably reduce the incidence and prevalence of B19 infection; thus, screening is required for epidemiologic surveillance and disease-prevention measures.

  10. [Beta thalassemia major and pregnancy during adolescence: report of two cases]. (United States)

    Trigo, Lucas Augusto Monteiro Castro; Surita, Fernanda Garanhani; Parpinelli, Mary Angela; Pereira, Belmiro Gonçalves; Fertrin, Kleber Yotsumoto; Costa, Maria Laura


    Beta thalassemia major is a rare hereditary blood disease in which impaired synthesis of beta globin chains causes severe anemia. Medical treatment consists of chronic blood transfusions and iron chelation. We describe two cases of adolescents with beta thalassemia major with unplanned pregnancies and late onset of prenatal care. One had worsening of anemia with increased transfusional requirement, fetal growth restriction, and placental senescence. The other was also diagnosed with hypothyroidism and low maternal weight, and was admitted twice during pregnancy due to dengue shock syndrome and influenza H1N1-associated respiratory infection. She also developed fetal growth restriction and underwent vaginal delivery at term complicated by uterine hypotonia. Both patients required blood transfusions after birth and chose medroxyprogesterone as a contraceptive method afterwards. This report highlights the importance of medical advice on contraceptive methods for these women and the role of a specialized prenatal follow-up in association with a hematologist.

  11. The role of beta-endorphin in the pathophysiology of major depression. (United States)

    Hegadoren, K M; O'Donnell, T; Lanius, R; Coupland, N J; Lacaze-Masmonteil, N


    A role for beta-endorphin (beta-END) in the pathophysiology of major depressive disorder (MDD) is suggested by both animal research and studies examining clinical populations. The major etiological theories of depression include brain regions and neural systems that interact with opioid systems and beta-END. Recent preclinical data have demonstrated multiple roles for beta-END in the regulation of complex homeostatic and behavioural processes that are affected during a depressive episode. Additionally, beta-END inputs to regulatory pathways involving feeding behaviours, motivation, and specific types of motor activity have important implications in defining the biological foundations for specific depressive symptoms. Early research linking beta-END to MDD did so in the context of the hypothalamic-pituitary-adrenal (HPA) axis activity, where it was suggested that HPA axis dysregulation may account for depressive symptoms in some individuals. The primary aims of this paper are to use both preclinical and clinical research (a) to critically review data that explores potential roles for beta-END in the pathophysiology of MDD and (b) to highlight gaps in the literature that limit further development of etiological theories of depression and testable hypotheses. In addition to examining methodological and theoretical challenges of past clinical studies, we summarize studies that have investigated basal beta-END levels in MDD and that have used challenge tests to examine beta-END responses to a variety of experimental paradigms. A brief description of the synthesis, location in the CNS and behavioural pharmacology of this neuropeptide is also provided to frame this discussion. Given the lack of clinical improvement observed with currently available antidepressants in a significant proportion of depressed individuals, it is imperative that novel mechanisms be investigated for antidepressant potential. We conclude that the renewed interest in elucidating the role of beta

  12. Seroprevalence of parvovirus B19 infection in patients with beta thalassemia major in Fayoum University Hospital

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    Mohamed E. Al Ghwass


    Conclusion: Parvovirus B19 infection is detected in high rates among children with beta thalassemia major. Measures to avoid iatrogenic and nosocomial transmission have to be implemented including screening of donated blood for B19 especially blood given to patients with hematological disorders. Also data from this study support the need for introduction of an approved B19 vaccine that primarily protects children with thalassemia major against that infection.

  13. Muscarinic supersensibility of anterior pituitary ACTH and beta-endorphin release in major depressive illness

    International Nuclear Information System (INIS)

    Risch, S.C.; Gillin, J.C.; Janowsky, D.S.


    Since numerious physiological systems display muscarinic receptor supersensitivity in major depressive illnesses, the authors have hypothesize that anterior pituitary release of ACTH and beta-Endorphin immunoreactivity may also be muscarinically supersensitive in depression. The studies were conducted under FDA-approved IND and with local human subjects committee approval. Plasma ACTH concentrations were determined as follows: samples were assayed in duplicate using equilibrium radioimmunoassay utilizing a rabbit anti-porcine ACTH antibody. Significance ofchanges in plasma cortisol, ACTH and beta-endorphin immunoreactivity after physostigmine and saline were determined by repeated measures analysis of variance. In all subject groups, physostigmine (relative to placebo) caused significant increases in plasma concentrations of cortisol, ACTH, and beta-endorphin immonoreactivity

  14. Mapping of a Leishmania major gene/locus that confers pentamidine resistance by deletion and insertion of transposable element

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    Coelho Adriano C.


    Full Text Available Pentamidine (PEN is an alternative compound to treat antimony-resistant leishmaniasis patients, which cellular target remains unclear. One approach to the identification of prospective targets is to identify genes able to mediate PEN resistance following overexpression. Starting from a genomic library of transfected parasites bearing a multicopy episomal cosmid vector containing wild-type Leishmania major DNA, we isolated one locus capable to render PEN resistance to wild type cells after DNA transfection. In order to map this Leishmania locus, cosmid insert was deleted by two successive sets of partial digestion with restriction enzymes, followed by transfection into wild type cells, overexpression, induction and functional tests in the presence of PEN. To determine the Leishmania gene related to PEN resistance, nucleotide sequencing experiments were done through insertion of the transposon Mariner element of Drosophila melanogaster (mosK into the deleted insert to work as primer island. Using general molecular techniques, we described here this method that permits a quickly identification of a functional gene facilitating nucleotide sequence experiments from large DNA fragments. Followed experiments revealed the presence of a P-Glycoprotein gene in this locus which role in Leishmania metabolism has now been analyzed.

  15. Genotyping of the 19-bp insertion/deletion polymorphism in the 5' flank of beta-hydroxylase gene by dissociation analysis of allele-specific PCR products

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Werge, Thomas


    The 19-bp insertion/deletion polymorphism in the 5' flank of the dopamine beta-hydroxylase (DBH) gene has been associated with psychiatric disorders. We have developed a simple, reliable and inexpensive closed-tube assay for genotyping of this polymorphism based upon T(m) determination of amplified...... and a conventional approach based upon agarose gel electrophoresis of amplified fragments revealed complete concordance between the two procedures. The insights obtained in this study may be utilized to develop assays based upon dissociation analysis of PCR products for genotyping of other insertion...

  16. In vivo immunologic selection of class I major histocompatibility complex gene deletion variants from the B16-BL6 melanoma. (United States)

    Talmadge, J E; Talmadge, C B; Zbar, B; McEwen, R; Meeker, A K; Tribble, H


    The mechanism by which tumor allografts escape host immunologic attack was investigated. B16-BL6 cells (the bladder 6 subline of the B16 melanoma) (H-2b) were transfected with a gene (Dd) encoding an allogeneic class I major histocompatibility complex antigen. Clones that expressed Dd antigen were injected into the footpads of nonimmune syngeneic mice, syngeneic immune mice, and nude mice. Under conditions of immunologic selection a clone that contained multiple copies of the transfected gene formed variants that lacked the transfected gene. Primary tumors and pulmonary metastases of immunized mice and pulmonary metastases of nonimmunized mice had lost the Dd gene and, in most cases, all of the associated plasmid. In contrast, in immunodeficient nude mice, primary tumors and pulmonary metastases retained the Dd gene and the associated plasmid. Deletion of genes encoding cell surface antigens may be one of the mechanisms by which allogeneic tumors escape immunologic attack.

  17. Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis. (United States)

    Mir-Coll, Joan; Duran, Jordi; Slebe, Felipe; García-Rocha, Mar; Gomis, Ramon; Gasa, Rosa; Guinovart, Joan J


    Glycogen accumulation occurs in beta cells of diabetic patients and has been proposed to partly mediate glucotoxicity-induced beta cell dysfunction. However, the role of glycogen metabolism in beta cell function and its contribution to diabetes pathophysiology remain poorly understood. We investigated the function of beta cell glycogen by studying glucose homeostasis in mice with (1) defective glycogen synthesis in the pancreas; and (2) excessive glycogen accumulation in beta cells. Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using pancreas-specific Cre lines. Glucose homeostasis was assessed by determining fasting glycaemia, insulinaemia and glucose tolerance. Beta cell mass was determined by morphometry. Glycogen was detected histologically by periodic acid-Schiff's reagent staining. Isolated islets were used for the determination of glycogen and insulin content, insulin secretion, immunoblots and gene expression assays. Gys1 knockout (Gys1 (KO)) mice did not exhibit differences in glucose tolerance or basal glycaemia and insulinaemia relative to controls. Insulin secretion and gene expression in isolated islets was also indistinguishable between Gys1 (KO) and controls. Conversely, despite effective glycogen overaccumulation in islets, mice with PTG overexpression (PTG(OE)) presented similar glucose tolerance to controls. However, under fasting conditions they exhibited lower glycaemia and higher insulinaemia. Importantly, neither young nor aged PTG(OE) mice showed differences in beta cell mass relative to age-matched controls. Finally, a high-fat diet did not reveal a beta cell-autonomous phenotype in either model. Glycogen metabolism is not required for the maintenance of beta cell function. Glycogen accumulation in beta cells alone is not sufficient to trigger the dysfunction or loss of these cells, or progression to diabetes.

  18. Countermeasure development for Rift Valley fever: deletion, modification or targeting of major virulence factor NSs. (United States)

    Lihoradova, Olga; Ikegami, Tetsuro


    Rift Valley fever (RVF) is a mosquito-borne zoonotic disease characterized by a high rate of abortion in ruminants, and febrile illness, hemorrhagic fever, retinitis and encephalitis in humans. RVF is caused by the RVF virus (RVFV), belonging to the genus Phlebovirus of the family Bunyaviridae . RVFV encodes a major virulence factor, NSs , which is dispensable for viral replication, yet required for evasion of host innate immune responses. RVFV NSs inhibits host gene upregulation at the transcriptional level, while promoting viral translation in the cytoplasm. In this article, we summarize the virology and pathology of RVF, and countermeasure development for RVF, with emphasis on NSs function and applications.

  19. Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a major metabolic gene.

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    Pep Charusanti


    Full Text Available Bacterial survival requires adaptation to different environmental perturbations such as exposure to antibiotics, changes in temperature or oxygen levels, DNA damage, and alternative nutrient sources. During adaptation, bacteria often develop beneficial mutations that confer increased fitness in the new environment. Adaptation to the loss of a major non-essential gene product that cripples growth, however, has not been studied at the whole-genome level. We investigated the ability of Escherichia coli K-12 MG1655 to overcome the loss of phosphoglucose isomerase (pgi by adaptively evolving ten replicates of E. coli lacking pgi for 50 days in glucose M9 minimal medium and by characterizing endpoint clones through whole-genome re-sequencing and phenotype profiling. We found that 1 the growth rates for all ten endpoint clones increased approximately 3-fold over the 50-day period; 2 two to five mutations arose during adaptation, most frequently in the NADH/NADPH transhydrogenases udhA and pntAB and in the stress-associated sigma factor rpoS; and 3 despite similar growth rates, at least three distinct endpoint phenotypes developed as defined by different rates of acetate and formate secretion. These results demonstrate that E. coli can adapt to the loss of a major metabolic gene product with only a handful of mutations and that adaptation can result in multiple, alternative phenotypes.

  20. Hypothalamic-pituitary-adrenal axis abnormalities in response to deletion of 11beta-HSD1 is strain-dependent

    NARCIS (Netherlands)

    Carter, R. N.; Paterson, J. M.; Tworowska, U.; Stenvers, D. J.; Mullins, J. J.; Seckl, J. R.; Holmes, M. C.


    Inter-individual differences in hypothalamic-pituitary-adrenal (HPA) axis activity underlie differential vulnerability to neuropsychiatric and metabolic disorders, although the basis of this variation is poorly understood. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has previously been

  1. Effect ALPHA Globalin Gene Deletion and GAMMA Globin Gene -158 (C/T) Polymorphism in BETA- Thalassaemic Patients

    International Nuclear Information System (INIS)

    EL Serafi, T.I.; Ismail, E.F.; Mahmoud, M.A.; Mohamed, M.A.; Ghattas, M.H.; Badran, D.I.; El Serafi, I.T.; Mohamed, H.S.


    The beta-thalassemias (β- thalassemias) are among the most common autosomal recessive disorders. They have a remarkably high frequency in the Mediterranean region and represent one of the most common genetic diseases in Egypt. In this study, the spectrum of P- thalassemia mutations and genotype-to-phenotype correlations were defined in 32 β- thalassaemic patients (β- thalassemias major and intermedia) with varying disease severity in two cities of the Suez Canal region. Ten different mutations were identified and the most frequent ones were: Isi-6 (T-C) (37.5%), IVSI-110 (G-A) (34.4%) and both IVSI-1 (G-A), IVSII-745 (C-G) and -102 (C-G) (12.5% each). There was a wide spectrum of phenotypic severity in all patients. We studied the Xmnl polymorphism (C/T) in γ- globin gene position -158 of P- thalassemia as a modulating factor of the disease severity. Presence of the polymorphism was found in two patients and this was not sufficient to explain the diversity of the phenotype encountered. Co-inheritance of alpha thalassaemia as a modulating factor was not evident in our patients. In conclusion, we have been unable to find a molecular basis for the benign clinical course in all our patients. Other genetic or acquired factors must be hypothesized which ameliorate the clinical condition.

  2. Effect of long-term transfusion therapy on the glycometabolic status and pancreatic beta cell function in patients with beta Thalassemia major

    Directory of Open Access Journals (Sweden)

    Kamalakshi G Bhat


    Full Text Available Background: Diabetes mellitus is a major complication of iron overload in patients with beta thalassemia major. Design: This is a descriptive study conducted in a Tertiary Care Teaching Hospital to analyze beta cell function and insulin resistance, and their relation to iron overload status in beta thalassemia major. Fasting glucose, two-hour post load glucose, fasting insulin, alanine amino transaminase (ALT, and ferritin were used as outcome measures. The homeostatic model assessment (HOMA model was used to calculate the beta cell function and insulin resistance index. Results: Of the 30 cases, 20% had impaired fasting glucose, 3.3% had impaired glucose tolerance, and none had diabetes. Fasting glucose was not significant between the cases and controls (P = 0.113. Fasting insulin (P = 0.001, ferritin (P = 0.001, and ALT (P = 0.001 levels were significantly high in the cases. Insulin resistance index was significantly higher in the cases (P = 0.001 as also the beta cell function (P = 0.001. With increase in age and the number of units transfused there is a decline in beta cell function, fasting insulin, and insulin resistance after attaining the maximum level. This suggests that initial insulin resistance is followed by insulin depletion due to loss of beta cell function, leading to diabetes mellitus. Conclusion: Impaired glucose tolerance (IGT and insulin resistance precede the onset of insulin-dependent diabetes and adequate chelation therapy is essential for delaying the onset or for prevention of diabetes.

  3. Regional consensus opinion for the management of Beta thalassemia major in the Arabian Gulf area (United States)


    Thalassemia syndrome has diverse clinical presentations and a global spread that has far exceeded the classical Mediterranean basin where the mutations arose. The mutations that give rise to either alpha or beta thalassemia are numerous, resulting in a wide spectrum of clinical severity ranging from carrier state to life-threatening, inherited hemolytic anemia that requires regular blood transfusion. Beta thalassemia major constitutes a remarkable challenge to health care providers. The complications arising due to the anemia, transfusional iron overload, as well as other therapy-related complications add to the complexity of this condition. To produce this consensus opinion manuscript, a PubMed search was performed to gather evidence-based original articles, review articles, as well as published work reflecting the experience of physicians and scientists in the Arabian Gulf region in an effort to standardize the management protocol. PMID:24044606

  4. A cross-sectional study of metabolic and endocrine complications in beta-thalassemia major

    International Nuclear Information System (INIS)

    Najafipour, F.; Aliasgarzadeh, A.; Aghamohamadzadeh, N.; Bahrami, A.; Mobasri, M.; Niafar, M.; Khoshbaten, M.


    Iron overload is a major problem in patients with beta-thalassemia major, and it has many structural and metabolic consequences. The aim of this study was evaluation of endocrine disturbances in patients with beta-thalassemia major who were older than 10 years of age. In this cross-sectional study, investigator collected demographic data and medical histories, as well as menstrual history in females, from the medical records of 56 patients with beta-thalassemia major. Patients were examined to determine their pubertal status and the standard deviation score for height for evaluation of short stature. For evaluation of glucose tolerance, a fasting blood glucose and oral glucose tolerance tests were performed. Evidence for diabetes mellitus was based on American Diabetes Association and World Health Organization criteria. Serum levels of calcium, phosphorous, thyroid-stimulating hormone, free thyroxin, luteinizing hormone and follicular-stimulating hormone and estradiol in girls and testosterone in boys were measured. The mean and standard deviation for age in the 56 patients (36 males and 20 females) was 15.62+-4.44 years. Diabetes mellitus was present in 5 patients (8.9%), impaired fasting glucose was found in 16 patients (28.6%) and an impaired glucose tolerance test was found in 4 patients (7.1%). Short stature (standard deviation score <-2) was seen in 25 (70%) boys and 14 (73%) girls. Impaired puberty was found in 40 patients (71%). Hypocalcaemia and primary overt hyperthyroidism were present in 23 (41%) and 9 patients (16%), respectively. Only eight patients (14.3%) had no endocrine abnormalities. Despite therapy with deferoxamine to treat iron overload, the risk of secondary endocrine dysfunction remained high. Hypogonadism was one of the most frequent endocrine complications. Impaired glucose tolerance, short stature, hypocalcemia, subclinical and overt hypothyroidism are also frequent. (author)

  5. The interaction of beta 2-microglobulin (beta 2m) with mouse class I major histocompatibility antigens and its ability to support peptide binding. A comparison of human and mouse beta 2m

    DEFF Research Database (Denmark)

    Pedersen, L O; Stryhn, A; Holter, T L


    of class I molecules are involved in peptide binding, whereas most of class I molecules are involved in beta 2m binding. We propose that mouse beta 2m interacts with the minor peptide binding (i.e. the "empty") fraction with a lower affinity than human beta 2m does, whereas mouse and human beta 2m interact......The function of major histocompatibility complex (MHC) class I molecules is to sample peptides derived from intracellular proteins and to present these peptides to CD8+ cytotoxic T lymphocytes. In this paper, biochemical assays addressing MHC class I binding of both peptide and beta 2-microglobulin...... (beta 2m) have been used to examine the assembly of the trimolecular MHC class I/beta 2m/peptide complex. Recombinant human beta 2m and mouse beta 2ma have been generated to compare the binding of the two beta 2m to mouse class I. It is frequently assumed that human beta 2m binds to mouse class I heavy...

  6. Purification, crystallization and preliminary X-ray analysis of a deletion mutant of a major buckwheat allergen

    International Nuclear Information System (INIS)

    Kezuka, Yuichiro; Itagaki, Takashi; Satoh, Rie; Teshima, Reiko; Nonaka, Takamasa


    A 16 kDa buckwheat protein (BWp16) is a major allergen responsible for immediate hypersensitivity reactions including anaphylaxis. An immunologically active mutant of BWp16 was prepared and a three-wavelength MAD data set was collected from a crystal of selenomethionine-labelled mutant protein. A 16 kDa buckwheat protein (BWp16) is a major allergen responsible for immediate hypersensitivity reactions including anaphylaxis. A deletion mutant of BWp16 (rBWp16ΔN) was overproduced and purified and was shown to be immunologically active. A three-wavelength MAD data set was collected from a crystal of selenomethionine-labelled rBWp16ΔN. The crystal belonged to the triclinic space group P1, with unit-cell parameters a = 28.39, b = 31.54, c = 32.20 Å, α = 111.92, β = 108.91, γ = 98.74°. One monomer was expected to be present in the asymmetric unit based on the calculated Matthews coefficient of 1.76 Å 3 Da −1

  7. Hypoparathyroidism and intracerebral calcification in patients with beta-thalassemia major

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    Karimi, M. [Iran-Shiraz-Namazee Hospital, Namazee Square, Hematology Research Center, Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:; Rasekhi, A.R. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:; Rasekh, M. [Iran-Shiraz-Namazee Hospital, Namazee Square, Department of Endocrinology and Metabolism, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:; Nabavizadeh, S.A. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:; Assadsangabi, R. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:; Amirhakimi, G.H. [Iran-Shiraz-Namazee Hospital, Namazee Square, Department of Endocrinology and Metabolism, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:


    Background: Hypoparathyroidism is one of the most important endocrine complications of thalassemia major. This study was conducted to evaluate the prevalence of intracerebral calcifications in patients with thalassemia with and without hypoparathyroidism. Methods: 47 beta-thalassemia patients with hypoparathyroidism underwent a brain CT scan to investigate the presence and extent of intracerebral calcification. 30 age- and sex-matched beta-thalassemic patients with normal parathyroid function who had undergone brain CT for headache, or some other minor neurologic problems were also enrolled in the study serving as controls. The amount of intracerebral calcification, hematologic parameters, and some clinical findings were compared between both groups. Results: Intracerebral calcification was present in 54.2% of beta-thalassemia patients with hypoparathyroidism. The most frequent sites of calcification were basal ganglia, and frontoparietal areas of the brain. Thalami, internal capsule, cerebellum and posterior fossa were other less frequently calcified regions of the brain. In contrast, there was no evidence of intracerebral calcifications in the 30 thalassemic patients with normal parathyroid function. There was not a statistically significant difference between serum ferritin concentrations in thalassemia patient with hypoparathyroidism and those with normal parathyroid function (2781 vs. 2178, P > 0.05). Conclusion: Intracranial calcification is a common finding in thalassemia patients with hypoparathyroidism, it can be extensive and involves most regions of the brain.

  8. Hypoparathyroidism and intracerebral calcification in patients with beta-thalassemia major

    International Nuclear Information System (INIS)

    Karimi, M.; Rasekhi, A.R.; Rasekh, M.; Nabavizadeh, S.A.; Assadsangabi, R.; Amirhakimi, G.H.


    Background: Hypoparathyroidism is one of the most important endocrine complications of thalassemia major. This study was conducted to evaluate the prevalence of intracerebral calcifications in patients with thalassemia with and without hypoparathyroidism. Methods: 47 beta-thalassemia patients with hypoparathyroidism underwent a brain CT scan to investigate the presence and extent of intracerebral calcification. 30 age- and sex-matched beta-thalassemic patients with normal parathyroid function who had undergone brain CT for headache, or some other minor neurologic problems were also enrolled in the study serving as controls. The amount of intracerebral calcification, hematologic parameters, and some clinical findings were compared between both groups. Results: Intracerebral calcification was present in 54.2% of beta-thalassemia patients with hypoparathyroidism. The most frequent sites of calcification were basal ganglia, and frontoparietal areas of the brain. Thalami, internal capsule, cerebellum and posterior fossa were other less frequently calcified regions of the brain. In contrast, there was no evidence of intracerebral calcifications in the 30 thalassemic patients with normal parathyroid function. There was not a statistically significant difference between serum ferritin concentrations in thalassemia patient with hypoparathyroidism and those with normal parathyroid function (2781 vs. 2178, P > 0.05). Conclusion: Intracranial calcification is a common finding in thalassemia patients with hypoparathyroidism, it can be extensive and involves most regions of the brain.

  9. A Comparison of Quality of Life between Adolescences with Beta Thalassemia Major and their Healthy Peers

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    Shahram Baraz


    Full Text Available Background The chronic genetic blood disorder, thalassemia, affects Quality of life (QOL negatively. Regarding this, if adolescences with thalassemia are treated well, they will grow into an adult who will have a good potential for participating in society. Objectives: to determine the strongest predictor of QOL, compare QOL between the adolescents with beta-type major and their peers in Abadan city. Materials and Methods This was a cross-sectional study; the population consisted of 65 beta thalassemia major patients and 65  healthy peers with the same ages as the witness group. The data collection tools included SF-36 questionnaire and a questionnaire for demographic information. Data analysis was performed using independent t-test, correlation and linear regression by SPSS-16. Results The results of the study revealed that there is a significant difference (P < 0.05 in the average quality of life between the two groups of the study. On the other hand, the results showed that there was a meaningful relation between different aspects of life quality and family history of thalassemia            (P< 0.05. Also, there was a negative correlation between quality of life and the frequency of blood transfusion per year (P< 0.05. Conclusion Adolescences with beta thalassemia major do not have a desirable quality of life, therefore, this fact shows the necessity of serious reforming in various fields of health care, treatment, family, social and financial support, and rehabilitation that need more attention from health care policymakers.

  10. Noninvasive analysis of skin iron and zinc levels in beta-thalassemia major and intermedia

    International Nuclear Information System (INIS)

    Gorodetsky, R.; Goldfarb, A.; Dagan, I.; Rachmilewitz, E.A.


    Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for noninvasive determination of iron and zinc in two distinct skin areas, representing predominantly dermal and epidermal tissues, in 56 patients with beta-thalassemia major and intermedia. The mean iron levels in the skin of patients with beta-thalassemia major and intermedia were elevated by greater than 200% and greater than 50%, respectively, compared with control values. The zinc levels of both skin areas examined were within the normal range. The data indicate that the rate and number of blood transfusions, which correlated well with serum ferritin levels (r . 0.8), are not the only factors that determine the amount of iron deposition in the skin (r less than 0.6). Other sources of iron intake contribute to the total iron load in the tissues, particularly in patients who are not given multiple transfusions. The noninvasive quantitation of skin levels may reflect the extent of iron deposition in major parenchymal organs. Repeated DXS examinations of the skin could monitor the clearance of iron from the tissues of patients with iron overload in the course of therapy with chelating agents

  11. Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection.

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    Magdalena Radwanska


    Full Text Available Effector responses induced by polarized CD4+ T helper 2 (Th2 cells drive nonhealing responses in BALB/c mice infected with Leishmania major. Th2 cytokines IL-4 and IL-13 are known susceptibility factors for L. major infection in BALB/c mice and induce their biological functions through a common receptor, the IL-4 receptor alpha chain (IL-4Ralpha. IL-4Ralpha-deficient BALB/c mice, however, remain susceptible to L. major infection, indicating that IL-4/IL-13 may induce protective responses. Therefore, the roles of polarized Th2 CD4+ T cells and IL-4/IL-13 responsiveness of non-CD4+ T cells in inducing non-healer or healer responses have yet to be elucidated. CD4+ T cell-specific IL-4Ralpha (Lck(creIL-4Ralpha(-/lox deficient BALB/c mice were generated and characterized to elucidate the importance of IL-4Ralpha signaling during cutaneous leishmaniasis in the absence of IL-4-responsive CD4+ T cells. Efficient deletion was confirmed by loss of IL-4Ralpha expression on CD4+ T cells and impaired IL-4-induced CD4+ T cell proliferation and Th2 differentiation. CD8+, gammadelta+, and NK-T cells expressed residual IL-4Ralpha, and representative non-T cell populations maintained IL-4/IL-13 responsiveness. In contrast to IL-4Ralpha(-/lox BALB/c mice, which developed ulcerating lesions following infection with L. major, Lck(creIL-4Ralpha(-/lox mice were resistant and showed protection to rechallenge, similar to healer C57BL/6 mice. Resistance to L. major in Lck(creIL-4Ralpha(-/lox mice correlated with reduced numbers of IL-10-secreting cells and early IL-12p35 mRNA induction, leading to increased delayed type hypersensitivity responses, interferon-gamma production, and elevated ratios of inducible nitric oxide synthase mRNA/parasite, similar to C57BL/6 mice. These data demonstrate that abrogation of IL-4 signaling in CD4+ T cells is required to transform non-healer BALB/c mice to a healer phenotype. Furthermore, a beneficial role for IL-4Ralpha signaling in L

  12. Frequency of hepatitis B and hepatitis C in multi - transfused beta thalassemia major patients

    International Nuclear Information System (INIS)

    Iqbal, M.M.; Hassan, S.; Aziz, S.


    To determine the frequency of hepatitis B and C virus infection among children with beta thalassemia major registered at Military Hospital Rawalpindi. Children attending Thalassemia Centre Military Hospital Rawalpindi for regular blood transfusion were registered. They belonged to different ethnic groups and came from different parts of the country. Their demographic data was recorded, detailed history taken and physical examination was carried out. Their serum samples were tested for hepatitis B surface antigen and anti HCV antibody assay with third generation commercial ELISA method. During the study; 141 patients of beta thalassemia major were screened. Out of them 50 patients (35.5% ,95% confidence interval 27.8-43.5)w ere found hepatitis C virus antibody positive and 1 patient (0.7 %) hepatitis B surface antigen positive. One patient (0.7%) had both hepatitis B and C virus infection. Mean age of hepatitis C infected patients was 10.4+3.85y ears (range 2-16 years). Mean age of uninfected patients was 6.1 + 3.59 years. (p value 0.000) In addition, the results indicate that higher prevalence of anti-HCV was significantly associated with longer duration of transfusion (p value <0.003). In spite of the fact that screened blood is used for transfusions, still a large number of patients have been found infected with hepatitis C. Therefore more accurate techniques are required for screening of blood to prevent transfusion associated transmission. (author)

  13. A gene encoding the major beta tubulin of the mitotic spindle in Physarum polycephalum plasmodia

    Energy Technology Data Exchange (ETDEWEB)

    Burland, T.G.; Paul, E.C.A.; Oetliker, M.; Dove, W.F.


    The multinucleate plasmodium of Physarum polycephalum is unusual among eucaryotic cells in that it uses tubulins only in mitotic-spindle microtubules; cytoskeletal, flagellar, and centriolar microtubules are absent in this cell type. The authors identified a ..beta..-tubulin cDNA clone, ..beta..105, which is shown to correspond to the transcript of the betC ..beta..-tubulin locus and to encode ..beta..2 tubulin, the ..beta.. tubulin expressed specifically in the plasmodium and used exclusively in the mitotic spindle. Physarum amoebae utilize tubulins in the cytoskeleton, centrioles, and flagella, in addition to the mitotic spindle. Sequence analysis shows that ..beta..2 tubulin is only 83% identical to the two ..beta.. tubulins expressed in amoebae. This compares with 70 to 83% identity between Physarum ..beta..2 tubulin and the ..beta.. tubulins of yeasts, fungi, alga, trypanosome, fruit fly, chicken, and mouse. On the other hand, Physarum ..beta..2 tubulin is no more similar to, for example, Aspergillus ..beta.. tubulins than it is to those of Drosophila melanogaster or mammals. Several eucaryotes express at least one widely diverged ..beta.. tubulin as well as one or more ..beta.. tubulins that conform more closely to a consensus ..beta..-tubulin sequence. The authors suggest that ..beta..-tubulins diverge more when their expression pattern is restricted, especially when this restriction results in their use in fewer functions. This divergence among ..beta.. tubulins could have resulted through neutral drift. For example, exclusive use of Physarum ..beta..2 tubulin in the spindle may have allowed more amino acid substitutions than would be functionally tolerable in the ..beta.. tubulins that are utilized in multiple microtubular organelles. Alternatively, restricted use of ..beta.. tubulins may allow positive selection to operate more freely to refine ..beta..-tubulin function.

  14. Bone metabolism and mineral density in patients with beta-thalassemia major

    International Nuclear Information System (INIS)

    Dundar, U.; Kupesiz, A.; Yesilipeck, A.; Ozdem, S.; Gultekin, M.; Gilgil, E.; Tuncer, T.


    To evaluate bone metabolism in patients with beta-thalassemia major and to determine the factors associated with the development of osteoporosis. We studied 25 patients with thalassemia major with a mean age of 18.4 years (rang 5-31), age and gender matched 24 healthy controls who were attending the outpatient physical medicine and rehabilitation clinic of Akdeniz University Hospital between January 2004 and March 2004 in Turkey. Bone mineral density (BMD) of lumbar spine (L-1-L4) and proximal femur were determined using dual x-ray absorptiometry (DXA). Venous blood samples were obtained for determination of blood cell count and markers of bone formation and resorption. The BMD values, both at lumbar and femoral neck levels were significantly lower in patients compared to controls. Serum N-telopeptide level was slightly higher, whereas osteocalcin was slightly lower in patients, however, the values were not statistically significant. Plasma levels of insulin like growth factor-1 (IGF-I) and insulin like growth factor for binding protein-3 (IGFBP-3) were significantly lower in patients. Also, serum levels of estradiol and progesterone in females, luteinizing, hormone and follicle-stimulating hormone in both genders were significantly lower in patients. Serum levels of free testosterone and total testosterone were lower in patients, but not statistically significant. Patients also had significantly higher serum phosphorous levels and lower serum calcitonin levels compared to controls. The BMD is decreased in thalassemic patients. Growth retardation, growth hormone/IGF-I/IGFP-3 axis dysfunction, gonadal dysfunction and hypothalomo-pituitary-gonadal axis dysfunction may be responsible for the development of osteoporosis in the patients with beta-thalassemia major. (author)

  15. Beta-lipotropin is the major component of the plasma opioid response to surgical stress in humans

    Energy Technology Data Exchange (ETDEWEB)

    Porro, C.A.; Facchinetti, F.; Bertellini, E.; Petraglia, F.; Stacca, R.; Barbieri, G.C.; Genazzani, A.R.


    There is growing experimental evidence that beta-endorphin immunoreactivity is raised by surgical stress in patients undergoing general anesthesia. As the assay methods employed to date did not allow to fully discriminate between beta-endorphin and its immediate precursor, beta-lipotropin, the authors have investigated in the present study plasma levels of these two peptides by separating them by chromatography on plasma extracts prior to radioimmunoassay. Beta-lipotropin, but not beta-endorphin, plasma levels were found to be significantly elevated during surgery in the general anesthesia group, while no change was found in either peptide concentration in the spinal one. Cortisol plasma levels also increased significantly 90 minutes after the beginning of surgery. Although the sampling time they adopted may have prevented them from detecting an early peak of beta-endorphin during the first 30 minutes of surgery, the major component of the pituitary opioid response to surgical stress appears to be related to beta-lipotropin. This is in agreement with results of experimental work on various kinds of stress in animals and humans and seems to rule out a role for plasma beta-endorphin in post-operative analgesia. 38 references, 1 figure, 1 table.

  16. beta-thalassaemia major hos børn og unge i Danmark

    DEFF Research Database (Denmark)

    Jung, Anne; Main, Katharina Maria; Scheibel, Elma


    . One patient had died. The body height was between 1.5 and -5.4 SDS (median -1.7) and the sitting height was -0.6 to -5.6 SDS (median -2.3). The bone age was delayed 1-5 years (median -2.5) in six out of ten examined patients, and puberty delayed in four out of five. A dilated left ventricle...... strategy. MATERIAL AND METHODS: During 1998-99 all Danish pediatric departments were contacted for identification of children aged 0-18 years with beta-thalassemia major. Blood transfusions and chelation therapy were registered, and for Eastern Denmark clinical, endocrine, cardiac, and serologic parameters....... An earlier and more effective iron chelation therapy together with improved patient support may reduce growth disturbances and endocrine and cardiac late effects....

  17. Endocrine dysfunction and growth retardation assessment in children with beta -thalassemia major

    International Nuclear Information System (INIS)

    Noureldin, A.M.; Ahmed, A.M.


    Children suffering from beta-thalassemia major are reported to have endocrine abnormalities and growth retardation. This study was carried out to study the cause of their growth retardation and determine the extent and rate of endocrine complications. Twenty beta-thalassemic major pubertal children, with mean baemoglobin and ferritin concentration of 8.8±0.6 and 3.597± 1.931, respectively, and twenty pubertal control children were used in the study. The anthropometric measurements that carried out revealed significant low growth rate in patient groups in comparison with control. Patients divided into two groups; I) D-thal with delayed growth and II) S-thal with stunted growth. Basal serum thyoid hormones (T 3 and T 4 ) and thyroid stimulating hormone (TSH) were measured in patient groups and control group. T 3 showed highly significant decrease (P 4 showed non-significant change and TSH showed highly significant increase (P<0.001). Serum growth hormone showed significant lower concentrations in patient groups with values of 2.163±0.9 ng/ml, (P<0.01) and 1.832±1.9ng/ml, (P<0.01) for delayed growth thalassemic group (D-thal) and stunted growth thalassemic group (S-thal), respectively. Serum concentration of insulin growth factor-1 (IGF-1) hormone was studied. D-thal and S-thal had significant lower basal IGF-1 concentrationsof-58.44% (P<0.001) for D-thal and -64.37%, (P<0.001) for S-thal

  18. Beta-cell specific deletion of Dicer1 leads to defective insulin secretion and diabetes mellitus

    DEFF Research Database (Denmark)

    Kalis, Martins; Bolmeson, Caroline; Esguerra, Jonathan L.S.


    -cells specific disruption of the Dicer1 gene using the Cre-lox system controlled by the rat insulin promoter (RIP). In contrast to their normoglycaemic control littermates (RIP-Cre(+/-) Dicer1(¿/wt)), RIP-Cre(+/-)Dicer1(flox/flox) mice (RIP-Cre Dicer1(¿/¿)) developed progressive hyperglycaemia and full...... revealed altered islet morphology, marked decreased ß-cell mass, reduced numbers of granules within the ß-cells and reduced granule docking in adult RIP-Cre Dicer1(¿/¿) mice. ß-cell specific Dicer1 deletion did not appear to disrupt fetal and neonatal ß-cell development as 2-week old RIP-Cre Dicer1...

  19. The interaction between beta 2-microglobulin (beta 2m) and purified class-I major histocompatibility (MHC) antigen

    DEFF Research Database (Denmark)

    Pedersen, L O; Hansen, A S; Olsen, A C


    been generated recently and this paper reports on a similar assay for the interaction between beta 2m and class I. As a model system human beta 2m binding to mouse class I was used. The assay is strictly biochemical using purified reagents which interact in solution and complex formation is determined...... by size separation. It is specific and highly sensitive. The observed affinity of the interaction, KD, is close to 0.4 nM. The rate of association at 37 degrees C is very fast (the ka is around 5 x 10(4)/M/s) whereas the dissociation is slow (the kd is around 8 x 10(-6)/s); the ratio of dissociation...

  20. Prospects and future of conservative management of beta thalassemia major in a developing country

    International Nuclear Information System (INIS)

    Rahman, M.; Lodhi, Y.


    Objective: To assess the efficacy, prospects and future of conservative management of beta thalassemia major patients in a developing country. Design: Patients registered at IHBTS were studied over a period of three years. They consented to being managed on moderate transfusion regimen, aiming to maintain a pre-transfusion haemoglobin(Hgb) level of 9.0 plus minus 1.0 g per dL. We studied their transfusion requirements, status for transfusion transmitted infections (TTls), serum ferritin levels and complications developing as a result of iron overload. Subjects: Initially all registered patients were included in this study. Sporadic patients as well as dropouts occurring due to any reason, (patients concurrently seeking treatment at other centres as well, or complying poorly to advised chelation therapy) were excluded from the study. The data presented here conforms to a cohort of 60 regular patients who adhered best to our selection criteria. Main Outcome Measures: 1) The study highlights the deficiencies and problems of conservative management for beta thalassemia major. 2) The major impact of our study is the message that conservative management in a poor country, like ours, is a no-win situation. 3) There is an urgent need to immediately start a prevention programme. Results: In the younger patients, blood consumption even on the moderate transfusion regimen is 120ml/kg/year, however with ascending age the consumption increases to 240ml/kg/year. A substantive number of the patients are either Hep C (35%) or Hep B (1.7%) positive. There are no HIV positive patients. Serum ferritin levels vary widely and could not be controlled due to poor compliance to chelation. 50% of the patients developed one or other complications of iron overload. The cost of treatment depending on the quality of care, is tremendous and beyond the reach of the common man. Conclusions: Conservative management may be the best alternative and at times the only hope for patients in our country

  1. Endocrinopathies in Turkish children with Beta thalassemia major: results from a single center study. (United States)

    Isik, Pamir; Yarali, Nese; Tavil, Betül; Demirel, Fatma; Karacam, Gülşah Bayram; Sac, Rukiye Unsal; Fettah, Ali; Ozkasap, Serdar; Kara, Abdurrahman; Tunc, Bahattin


    The endocrinological complications in β-thalassemia major patients do affect the life quality to a large extend. In this study, the endocrinological complications of 47 β-thalassemia patients, who have been followed-up at our hospital's pediatric hematology department, were evaluated. Out of β-thalassemia major cases included to this study, the 55.3% was male and 44.7% was female. The patients' mean levels of ferritin, whose mean age was 10.0 ± 4.5 years (2-20 years), were 2497 ± 1469 ng/mL (472-8558 ng/mL). At least one endocrinological pathology in 27 out of 47 (57.4%) and more than one endocrinological pathology in 14 out of 47 (29.7%) thalassemia patients were observed. The most frequently observed complication in followed-up cases was vitamin D insufficiency and deficiency (78.2%). The other complications in decreasing order were pubertal failure (41.6%), growth retardation (25.5%), decreased bone-mineral density (22.2%), secondary hyperparathyroidism (11.5%), overt hypothyroidism (4.25%), subclinical hypothyroidism (2.12%), and impaired glucose tolerance (2.12%). There was no statistically significant difference between serum mean ferritin level and endocrin complications (P > .05). Four patients (8.5%) had decreased signal intensity in pituitary magnetic resonance imaging (MRI) but this finding was not associated with ferritin levels (P = .87). MRI parameters were similar between patients with and without gonadal dysfunction. Mean height of the pituitary gland was 4.98 ± 1.1 mm (3-9 mm) and this was similar to those normal values in the literature. Ferritin levels were not correlated with pituitary height (P > .05). Beta thalassemia major, having the potential of leading to multisystemic complications, is a chronic disease that should be treated and followed-up by a multidisciplinary approach. Due to frequently encountered endocrinological complications, beta thalassemic patients should be followed-up regularly by hematology and endocrinology

  2. Beta thalassemia major: The effect of age on glomerular filtration rate

    Directory of Open Access Journals (Sweden)

    Majid Malaki


    Full Text Available Thalassemia is a common hereditary hemoglobinopathy disorder that affects many organs in the body. Estimation of kidney function is important, as it is the vital organ that plays the major role in the elimination of accumulated iron as well as the chelating drugs that have to be used as therapy. Sixty- three patients aged 1-29 years, with a mean ± SD of 14 ± 6.7 years, affected with beta- thalassemia major in Tabriz Children′s Hospital were evaluated for their renal function on the basis of their age, serum iron, serum ferritin and serum creatinine levels along with two methods of estimating glomerular filtration rate (GFR; by Schwartz method for those under 18 years old and using Modification of Diet in Renal Disease (MDRD formula for those who were 18 years and above. Elevation of serum creatinine denoting renal dysfunction was not seen in our patients, but hyperfiltration was a common finding. An increasing GFR was observed, which corresponded to age, but no relationships were seen between serum iron, serum ferritin, regular blood transfusion, chelating therapy to GFR.

  3. MRI evaluation of tissue iron burden in patients with {beta}-thalassaemia major

    Energy Technology Data Exchange (ETDEWEB)

    Argyropoulou, Maria I.; Astrakas, Loukas [University of Ioannina, Radiology Department, Medical School, Ioannina (Greece)


    {beta}-Thalassaemia major is a hereditary haemolytic anaemia that is treated with multiple blood transfusions. A major complication of this treatment is iron overload, which leads to cell death and organ dysfunction. Chelation therapy, used for iron elimination, requires effective monitoring of the body burden of iron, for which serum ferritin levels and liver iron content measured in liver biopsies are used as markers, but are not reliable. MRI based on iron-induced T2 relaxation enhancement can be used for the evaluation of tissue siderosis. Various MR protocols using signal intensity ratio and mainstream relaxometry methods have been used, sometimes with discrepant results. Relaxometry methods using multiple echoes achieve better sampling of the time domain in which relaxation mechanisms take place and lead to more precise results. In several studies the MRI parameters of liver siderosis have failed to correlate with those of other affected organs, underlining the necessity for MRI iron evaluation in individual organs. Most studies have included children in the evaluated population, but MRI data on very young children are lacking. Wider application of relaxometry methods is indicated, with the establishment of universally accepted MRI protocols, and further studies, including young children, are needed. (orig.)

  4. Deletion of Irs2 causes reduced kidney size in mice: role for inhibition of GSK3beta?

    LENUS (Irish Health Repository)

    Carew, Rosemarie M.


    Abstract Background Male Irs2-\\/- mice develop fatal type 2 diabetes at 13-14 weeks. Defects in neuronal proliferation, pituitary development and photoreceptor cell survival manifest in Irs2-\\/- mice. We identify retarded renal growth in male and female Irs2-\\/- mice, independent of diabetes. Results Kidney size and kidney:body weight ratio were reduced by approximately 20% in Irs2-\\/- mice at postnatal day 5 and was maintained in maturity. Reduced glomerular number but similar glomerular density was detected in Irs2-\\/- kidney compared to wild-type, suggesting intact global kidney structure. Analysis of insulin signalling revealed renal-specific upregulation of PKBβ\\/Akt2, hyperphosphorylation of GSK3β and concomitant accumulation of β-catenin in Irs2-\\/- kidney. Despite this, no significant upregulation of β-catenin targets was detected. Kidney-specific increases in Yes-associated protein (YAP), a key driver of organ size were also detected in the absence of Irs2. YAP phosphorylation on its inhibitory site Ser127 was also increased, with no change in the levels of YAP-regulated genes, suggesting that overall YAP activity was not increased in Irs2-\\/- kidney. Conclusions In summary, deletion of Irs2 causes reduced kidney size early in mouse development. Compensatory mechanisms such as increased β-catenin and YAP levels failed to overcome this developmental defect. These data point to Irs2 as an important novel mediator of kidney size.

  5. The survival analysis of beta thalassemia major patients in South East of Iran

    International Nuclear Information System (INIS)

    Roudbari, M.; Soltani-Rad, M.; Roudbari, S.


    The objective was to determine the survival of beta-thalassemia major patients with transfusion, and its related factors in Southeast of Iran. This cross-sectional study was performed in Zahedan, Iran in 2007. The sample included patients who were referred from all over the Zahedan Thalassemia Center from 1998 to 2006. The data were collected using the patient's records, which were recorded by the staff during transfusion. The data included demographic and medical information blood group, blood RH, the kind of transfused blood [KTB], annual number of transfusions [ANOT], accompanied disease [AD], Hemoglobin [Hb] and ferritin level. For data analysis, the Kaplan-Meyer method, and Long Rank test together with Cox Regression were used. Forty-six of 578 patients died and 99% survived for the first year. The ages survival proportions were 5 (97.9%), 10 (97%), 15 (92.1%), and 20 (81.2%) years. The survival time showed significant relationships with the ANOT p=0.0053, KTB p=0.003, Hb=0.002 and ferritin level p=0.0087, and AD p=0.00. Using regular transfusion, paying attention to screening of transfused blood, increasing the families knowledge on the disease to prevent the bearing of thalassemia fetus, are recommended; finally, the detection and treating of the AD, are of great importance to extend the lifetime of the patients. (author)

  6. [Long-term effects of combined therapy in patients with beta-thalassemia major]. (United States)

    Bagnulo, S; Giannini, A M; Moscatelli, F; Stragapede, L; Acquafredda, A; Dammacco, A


    We evaluated therapy complications in 19 beta-thalassemia major patients (mean age from 3 years/5 months and 1 years/6 months) who were followed at II Pediatric Department-University of Bari. 3 out of 19 patients underwent allogenic BMT from matched related donor; 2 out of 19 underwent splenectomy. All of them were receiving hypertransfusion therapy and continuous chelation with DFO. In all patients we performed physical examination, laboratory assays, cardiac and endocrinologic function tests, serum HBV-HCV-HIV antibodies, otoscopy and audiometric test, fundus oculi, skeletal x-ray. 1 out of 19 patients, who was under 15, had a slight dilatation of left ventricle and arythmia. All patients were HBsAb positive. 4/19 patients were HCV Ab positive (ELISA test) with an increase in ALT-AST serum levels since at least 6 months. In 3 of them we assessed RIBA test, always positive. 3 of them underwent liver biopsy (1 iron overload 2 chronic active hepatitis). All patients were HIV Ab negative. 4/15 patients revealed low GH levels after Arginina test. 13 pre-pubescent patients had normal results with GNRH test but lower results after FSH test. 1 pubescent patient had gonadotropic hypophyseal deficit. 4 patients had subclinic hypothiroidism. We couldn't find any sequelas in bone-eyes-ears. Hypertransfusion therapy, chelation, profilaxis of infections improved length and quality of life in thalassemic patients. Hypogonadotropic hypogonadism remains a serious sequela and we think it needs to be treated.

  7. Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

    Directory of Open Access Journals (Sweden)

    Murtadha Al-Khabori


    Full Text Available Objectives: Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX side effects in patients with thalassemia major or intermedia.Methods: A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period.Results: Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline, feeling unwell (2, severe diarrhea (1, pregnancy (1, death unrelated to chelator (2 and rise in serum transaminases (2. Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013.Conclusion: Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings.

  8. Survival Analysis and its Associated Factors of Beta Thalassemia Major in Hamadan Province

    Directory of Open Access Journals (Sweden)

    Reza Zamani


    Full Text Available Background: There currently is a lack of knowledge about the long-term survival of patients with beta thalassemia (BT, particularly in regions with low incidence of the disease. The aim of the present study was to determine the survival rate of the patients with BT major and the factors associated with the survival time. Methods: This retrospective cohort study was performed in Hamadan province, located in the west of Iran. The study included patients that referred to the provincial hospitals during 16 year period from 1997 to 2013. The follow up of each subject was calculated from the date of birth to the date of death. Demographic and clinical data were extracted from patients’ medical records using a checklist. Statistical analysis included the Kaplan-Meier method to analyze survivals, log-rank to compare curves between groups, and Cox regression for multivariate prognostic analysis. Results: A total of 133 patients with BT major were enrolled, 54.9% of whom were male and 66.2% were urban. The 10-, 20- and 30-year survival rate for all patients were 98.3%, 88.4% and 80.5%, respectively. Based on hazard ratio (HR, we found that accompanied diseases (P=0.01, blood type (P=0.03 and residency status (P=0.01 were significant predictors for the survival time of patients. Conclusion: The survival rate of BT patients has improved. Future researches such as prospective designs are required for the estimation of survival rate and to find other prognostic factors, which have reliable sources of data.

  9. Effect of Average Annual Mean Serum Ferritin Levels on QTc Interval and QTc Dispersion in Beta-Thalassemia Major

    Directory of Open Access Journals (Sweden)

    Yazdan Ghandi


    Full Text Available Background There is evidence indicating impaired cardiomyocytic contractility, delayed electrical conduction and increased electrophysiological heterogeneities due to iron toxicity in beta-thalassemia major patients. In the present study, we compared the electrocardiographic and echocardiographic features of beta-thalassemia major patients with a healthy control group. Materials and Methods The average annual serum ferritin levels of fifty beta-thalassemia major patients were assessed. For each patient, corrected QT (QTc intervals and QTc dispersions (QTcd were calculated and V1S and V5R were measured. All subjects underwent two-dimensional M-mode echocardiography and Doppler study and were compared with 50 healthy subjects as a control group. Results QTc interval and dispersion were significantly higher in beta-thalassemia major patients (P= 0.001. The mean V5R (20.04 ± 4.34 vs. 17.14 ± 2.55 mm and V1S (10.24 ± 2.62 vs. 7.83 ± 0.38 mm showed considerably higher mean values in patients in comparison with control group.Peak mitral inflow velocity at early diastole and early to late ratio in the case- group was markedly higher(P

  10. Shortened of the crown and root lengths of the mandibular permanent molar in beta major thalassemia children

    Directory of Open Access Journals (Sweden)

    Indra Primathena


    Full Text Available Beta major thalassemia is a genetically inherited blood disorder due to a genetic mutation on the polypeptide chains of hemoglobin which is manifested in the growth and development of the tooth. The objectives of the investigation were to obtain differences of the crown and root lengths of the mandibular first right side permanent molar between beta major thalassemia children and normal children group at the matching ages of 11 to 13 years old. The descriptive comparative method was used in the study and samples were selected using the purposive sampling technique. Sample numbers, which were obtained using the consecutive sampling technique, consists of 12 children of beta major thalassemia and 12 of normal children at the matching ages of 11 to 13 years. Periapical radiographs of both thalassemia and normal children were administered using the method of Seow and Lai. Data were analyzed using t-test method. The study revealed that the crown and root lengths of the mandibular first right side permanent molar of beta major thalassemia children were shorter than normal children at the ages of 11 to 13 years.

  11. Imaging manifestations of acquired elastopathy resembling pseudoxanthoma elasticum in patients with beta thalassaemia major and sickle cell disease

    International Nuclear Information System (INIS)

    Narayana, Harish; Cheng, Ken; Lau, Ken; Harish, Radhika; Bowden, Donald K.


    Development of an acquired systemic elastopathy resembling pseudoxanthoma elasticum in patients with chronic haemoglobinopathies such as beta thalassaemia major and sickle cell disease is well documented. There is paucity of any comprehensive literature on the radiological manifestations of this entity. This pictorial review aims to describe and illustrate the multi system and multi modality imaging findings of this condition.

  12. Prevalence and spectrum of large deletions or duplications in the major long QT syndrome-susceptibility genes and implications for long QT syndrome genetic testing. (United States)

    Tester, David J; Benton, Amber J; Train, Laura; Deal, Barbara; Baudhuin, Linnea M; Ackerman, Michael J


    Long QT syndrome (LQTS) is a cardiac channelopathy associated with syncope, seizures, and sudden death. Approximately 75% of LQTS is due to mutations in genes encoding for 3 cardiac ion channel α-subunits (LQT1 to LQT3). However, traditional mutational analyses have limited detection capabilities for atypical mutations such as large gene rearrangements. We set out to determine the prevalence and spectrum of large deletions/duplications in the major LQTS-susceptibility genes in unrelated patients who were mutation negative after point mutation analysis of LQT1- to LQT12-susceptibility genes. Forty-two unrelated, clinically strong LQTS patients were analyzed using multiplex ligation-dependent probe amplification, a quantitative fluorescent technique for detecting multiple exon deletions and duplications. The SALSA multiplex ligation-dependent probe amplification LQTS kit from MRC-Holland was used to analyze the 3 major LQTS-associated genes, KCNQ1, KCNH2, and SCN5A, and the 2 minor genes, KCNE1 and KCNE2. Overall, 2 gene rearrangements were found in 2 of 42 unrelated patients (4.8%, confidence interval 1.7 to 11). A deletion of KCNQ1 exon 3 was identified in a 10-year-old Caucasian boy with a corrected QT duration of 660 ms, a personal history of exercise-induced syncope, and a family history of syncope. A deletion of KCNQ1 exon 7 was identified in a 17-year-old Caucasian girl with a corrected QT duration of 480 ms, a personal history of exercise-induced syncope, and a family history of sudden cardiac death. In conclusion, because nearly 5% of patients with genetically elusive LQTS had large genomic rearrangements involving the canonical LQTS-susceptibility genes, reflex genetic testing to investigate genomic rearrangements may be of clinical value. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Morphological and dimensional characteristics of dental arch in children with beta thalassemia major

    Directory of Open Access Journals (Sweden)

    Disha Kumar


    Full Text Available Background and Objectives: The aim of this study was to examine the arch dimensions of beta thalassemia major patients in comparison with normal individuals. Materials and Methods: Dental arch dimensions were compared between thalassemic patients and normal individuals in the age group of 12–16 years in the maxillary and mandibular arch corresponding to each other regarding age, sex and Angle's molar relationship. A total number of sixty cases in each group were taken. Maxillary and mandibular impressions were made with alginate for all the sixty participants in each group and poured with die stone. Measurement of inter incisor, inter canine, inter premolar and intermolar arch width, arch depth, right anterior, right posterior, left anterior, and left posterior arch length was carried out from each cast using digital Vernier caliper.Results: Unpaired t-test was used for comparison between the two groups. Statistically, a significant difference was found between the case and control groups in the maxillary arch in intercanine width, inter premolar width, intermolar width, right anterior arch length, right posterior arch length, and left anterior arch length. However, no statistically significant difference was found between the groups in inter incisor width, left posterior arch length, and arch depth in the maxillary arch. In the mandibular arch, statistically significant difference was found between the case and control groups in inter canine width, inter premolar width, inter molar width, and left anterior arch length. However, no statistically significant difference was found between the case and control groups in the mandibular arch in interincisor width, right anterior arch length, right posterior arch length, and left posterior arch length. Conclusion: Dental arch widths and arch lengths were significantly reduced in thalassemic patients as compared to normal individuals for the maxillary and mandibular arches.

  14. Anxiety, depression and quality of life in patients with beta thalassemia major and their caregivers. (United States)

    Yengil, Erhan; Acipayam, Can; Kokacya, Mehmet Hanifi; Kurhan, Faruk; Oktay, Gonul; Ozer, Cahit


    Mental health and health related quality of life is commonly affected in patients with chronic problems and their caregivers. In the present study, it was aimed to assess depression and anxiety in patients with beta thalassemia major (BTM) and in their caregivers; and to evaluate effects of these disorders on quality of life. The study was carried out in a district Hereditary Hemoglobinopathy Center and included 88 patients with BTM and 63 of their caregivers. All subjects were assessed using Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Short Form-36 (SF-36) by a trained psychiatry resident via face-to-face interview. The BDI scores were 17 or above in 20.5% of the patients with BTM and 28.6% of their caregivers (P = 0.248). Of the patients with BTM, there were mild anxiety symptoms in 19.3%, while moderate and severe anxiety symptoms in 14.8% and 4.5%, respectively. Anxiety levels were similar between the patients with BTM and their caregivers (P = 0.878). It was found that BDI and BAI scores were negatively correlated to scores of physical health and mental health components of SF-36 in patients with BTM and their caregivers. In linear regression analysis, it was seen that depression affected physical and mental health of the patients with BTM and their caregivers regardless from anxiety. BTM leads an increase in the frequency of depression and anxiety in both patients and their caregivers, and affects negatively physical and mental components of quality of life.

  15. Quality of life among Iranian patients with beta-thalassemia major using the SF-36 questionnaire

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    Sezaneh Haghpanah

    Full Text Available CONTEXT AND OBJECTIVE Patients with beta-thalassemia major (β-TM experience physical, psychological and social problems that lead to decreased quality of life (QoL. The aim here was to measure health-related QoL and its determinants among patients with β-TM, using the Short Form-36 (SF-36 questionnaire. DESIGN AND SETTING Cross-sectional study at the Hematology Research Center of Shiraz University of Medical Sciences, in southern Iran. METHODS One hundred and one patients with β-TM were randomly selected. After the participants' demographics and disease characteristics had been recorded, they were asked to fill out the SF-36 questionnaire. The correlations of clinical and demographic factors with the QoL score were evaluated. RESULTS There were 44 men and 57 women of mean age 19.52 ± 4.3 years (range 12-38. On two scales, pain (P = 0.041 and emotional role (P = 0.009, the women showed significantly lower scores than the men. Lower income, poor compliance with iron-chelating therapy and presence of comorbidities were significantly correlated with lower SF-36 scores. These factors were also found to be determinants of worse SF-36 scores in multivariate analysis. CONCLUSIONS We showed that the presence of disease complications, poor compliance with iron-chelating therapy and poor economic status were predictors of worse QoL among patients with β-TM. Prevention and proper management of disease-related complications, increased knowledge among patients regarding the importance of managing comorbidities and greater compliance with iron-chelating therapy, along with psychosocial and financial support, could help these patients to cope better with this chronic disease state.

  16. Effect of nutrition support on immunity in paediatric patients with beta-thalassaemia major. (United States)

    Tienboon, Prasong


    Nutritional deficiencies have been variably observed in thalassaemia and the aetiology of many of the immune abnormalities in thalassaemic children are poorly defined. Therefore, we tested the hypothesis that certain immune abnormalities have a nutritional basis. Nutritional status, selective quantitative and functional indices of immunity were studied in twelve children (7 females, 5 males; mean age 28 months, SD 5 and range 19.8-35.5), with thalassaemia major before and after a one month period of intensive nutrition support (the study diet consisted of 'Enfapro' liquid formula (Mead Johnson) with added dextrose and corn oil to achieve a caloric density of 1.1 kcal/cc in addition to vitamins and minerals). Each child was provided approximately 150 kcal/day and 4 g of protein/day. Lymphocyte proliferation to Concanavalin A (Con A) (P = 0.008) and Purified Protein Derivative (PPD) (P = 0.002) was depressed upon entry into the study, however the response to Con A attained normal values by the end of the intervention. Compared to baselines, the proliferative response to Con A (P = 0.005) and Phytohemagglutinin A (PHA) (P = 0.031) both improved after the nutrition support. Although there was no general correlation of zinc status with lymphocyte proliferation, normal baseline zinc status was associated with improvement of proliferation. The %CD4 increased (P = 0.036), primarily because of a decrease in total lymphocytes and to lesser extent a decrease in CD8 lymphocytes. Serum immunoglobulin concentrations were found to be elevated on admission but were not significantly affected by the nutrition intervention. C3 concentrations were uniformly depressed on admission but increased by the end of the study protocol (P = 0.037). C4 and CH50 activity were not significantly influenced by the intervention. In conclusion, children with beta thalassaemia have abnormalities of lymphocyte function as well as key complement components that are responsive to nutrition support. In

  17. [Pretreatment doses of antithymocyte globubin-fresenius for allogeneic hematopoietic stem cell transplantation for beta-thalassemia major]. (United States)

    Li, Chunfu; Wang, Yanhua; Wu, Xuedong; Pei, Fuyu; He, Yuelin; Feng, Xiaoqin; Liu, Huaying


    To investigate the effects of different doses of antithymocyte globubin-fresenius (ATG-F) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with beta-thalassemia Major. Sixty-four children with beta-thalassemia major undergoing allo-HSCT were divided into two equal groups to receive ATG-F pretreatments at high (30 mg/kg) or low (15 mg/kg) doses as part of the conditioning regimen including mainly cyclophosphamide, busulfan, fludarabine, and thiotepa. The outcomes of the patients were compared between the two groups. No obvious difference were noted in the time to leukocyte and platelet engraftment between the two groups. The incidence of grade II-IV acute graft-versus-host disease (aGVHD) appeared to be higher in the low-dose group than in the high-dose group (12.5% vs 9.4%). The incidence of grade III-IV aGVHD was also higher in the low dose group (12.5% vs 6.3%), but the difference was not statistically significant. Application of high-dose ATG-F was associated with a higher rate of probable and possible fungal infection (P<0.05). The two doses of ATG-F is feasible as a part of the conditioning regimen for allo-HSCT in children with beta-thalassemia major.

  18. The pancreas in {beta}-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbunces

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    Papakonstantinou, Olympia [University Hospital of Heraklion, Medical School of Crete, Department of Radiology, Heraklion, Crete (Greece); Attikon Hospital, 2nd Department of Radiology, Athens (Greece); Ladis, Vasilios; Kostaridou, Stavroula; Berdousi, Helen; Kattamis, Christos [Thalassemia Unit, University of Athens, ' ' Aghia Sophia' ' Children' s Hospital, Athens (Greece); Maris, Thomas; Gourtsoyiannis, Nicholas [University Hospital of Heraklion, Medical School of Crete, Department of Radiology, Heraklion, Crete (Greece)


    The study aims at describing the MR features of pancreas in beta-thalassemia major, investigating the relations between MR findings and glucose disturbances and between hepatic and pancreatic siderosis. Signal intensity ratios of the pancreas and liver to right paraspinous muscle (P/M, L/M) were retrospectively assessed on abdominal MR imaging studies of 31 transfusion-dependent patients with beta-thalassemia major undergoing quantification of hepatic siderosis and 10 healthy controls, using T1- (120/4/90), intermediate in and out of phase - (120/2.7, 4/20), and T2*-(120/15/20) weighted GRE sequences. Using the signal drop of the liver and pancreas on opposed phase images, we recorded serum ferritin and results of oral glucose tolerance test (OGTT). Decreased L/M and P/M on at least the T2* sequence were noticed in 31/31 and 30/31 patients, respectively, but no correlation between P/M and L/M was found. Patients with pathologic OGTT displayed a higher degree of hepatic siderosis (p < 0.04) and signal drop of pancreas on opposed phase imaging (p < 0.025), implying fatty replacement of pancreas. P/M was neither correlated with glucose disturbances nor serum ferritin. Iron deposition in the pancreas cannot be predicted by the degree of hepatic siderosis in beta-thalassemia major. Fatty replacement of the pancreas is common and may be associated with glucose disturbances. (orig.)

  19. Resolution of alloimmunization and refractory autoimmune hemolytic anemia in a multi-transfused beta-thalassemia major patient

    Directory of Open Access Journals (Sweden)

    Joseph Philip


    Full Text Available Beta-thalassemia is one of the most prevalent autosomal disorders, which affect more than 400,000 newborn per year worldwide. In India, the carrier rate of beta-thalassemia varies from 3-17%. The overall rate of alloimmunization in thalassemia patients has been reported to be 5-30% in the world, which is mostly contributed by the alloimmunization to minor blood group antigen. Among Asians, the incidence of red cell alloimmunization is 22%. The recommended treatment for beta-thalassemia major is regular blood transfusion every 3 to 4 weeks. The development of anti-red cell antibodies (alloantibodies and/or autoantibodies can significantly complicate transfusion therapy. Alloantibodies are commonly associated with red cell hemolysis. Red cell autoantibodies appear less frequently, but they can result in clinical hemolysis called autoimmune hemolytic anemia (AIHA, and in difficulty in cross-matching blood. Patients with autoantibodies may have a higher transfusion rate and often require immunosuppressive drugs or alternative treatments including intravenous immunoglobulin (IVIg and rituximab (anti-CD20 monoclonal antibody.

  20. Adrenal glands in beta-thalassemia major: magnetic resonance (MR) imaging features and correlation with iron stores

    International Nuclear Information System (INIS)

    Drakonaki, Eleni; Papakonstantinou, Olympia; Maris, Thomas; Gourtsoyiannis, Nicholas; Vasiliadou, Artemis; Papadakis, Alex


    This study aimed at describing the magnetic resonance (MR) imaging features of the adrenal glands in beta-thalassemic patients and at investigating the relation between adrenal and hepatic siderosis. Adrenal signal intensity (SI) was retrospectively assessed on abdominal MR studies of 35 patients with beta-thalassemia major undergoing quantification of hepatic siderosis and 12 healthy controls, using T1- (120/4/90), intermediate - (120/4/20), and T2*- (120/15/20) weighted GRE sequences. Adrenal SI was graded as grade 0 (normal SI on all sequences), grade 1 (hypointensity on T2* alone), or grade 2 (hypointensity on at least T2*). Adrenal size was measured in the thalassemic patients and compared with normative data. Liver-to-muscle (L/M) SI ratios, expressing hepatic siderosis, were estimated on each sequence. Serum ferritin levels were recorded. Adrenal hypointensity (grades 1 and 2) was noted in 24/35 (68.6%) patients. L/M ratios correlated significantly with adrenal SI in all sequences. Patients with grade 1 and grade 2 adrenal SI had significantly decreased L/M ratios compared with grade 0. Serum ferritin correlated significantly with L/M values but not with adrenal SI. Adrenal size was within normal limits. Diffuse hypointensity in normal-sized adrenals is a common MR finding in beta-thalassemic patients and correlates with the degree of hepatic siderosis. (orig.)

  1. Adrenal glands in beta-thalassemia major: magnetic resonance (MR) imaging features and correlation with iron stores

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    Drakonaki, Eleni; Papakonstantinou, Olympia; Maris, Thomas; Gourtsoyiannis, Nicholas [University Hospital of Heraklion, Department of Radiology, Heraklion (Greece); Vasiliadou, Artemis [Aghios Georgios Hospital of Chania, Thalassemia Unit, Chania (Greece); Papadakis, Alex [Venizelion Hospital of Heraklion, Thalassemia Unit, Heraklion (Greece)


    This study aimed at describing the magnetic resonance (MR) imaging features of the adrenal glands in beta-thalassemic patients and at investigating the relation between adrenal and hepatic siderosis. Adrenal signal intensity (SI) was retrospectively assessed on abdominal MR studies of 35 patients with beta-thalassemia major undergoing quantification of hepatic siderosis and 12 healthy controls, using T1- (120/4/90), intermediate - (120/4/20), and T2*- (120/15/20) weighted GRE sequences. Adrenal SI was graded as grade 0 (normal SI on all sequences), grade 1 (hypointensity on T2* alone), or grade 2 (hypointensity on at least T2*). Adrenal size was measured in the thalassemic patients and compared with normative data. Liver-to-muscle (L/M) SI ratios, expressing hepatic siderosis, were estimated on each sequence. Serum ferritin levels were recorded. Adrenal hypointensity (grades 1 and 2) was noted in 24/35 (68.6%) patients. L/M ratios correlated significantly with adrenal SI in all sequences. Patients with grade 1 and grade 2 adrenal SI had significantly decreased L/M ratios compared with grade 0. Serum ferritin correlated significantly with L/M values but not with adrenal SI. Adrenal size was within normal limits. Diffuse hypointensity in normal-sized adrenals is a common MR finding in beta-thalassemic patients and correlates with the degree of hepatic siderosis. (orig.)

  2. beta-Thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0]. (United States)

    Adams, J G; Steinberg, M H; Newman, M V; Morrison, W T; Benz, E J; Iyer, R


    Hemoglobin Vicksburg was discovered in a 6-year-old Black boy who had been anemic since infancy. Examination of his hemolysate revealed 87.5% Hb F, 2.4% Hb A2, and 7.6% Hb Vicksburg, which had the electrophoretic and chromatographic properties of Hb A. Structural analysis of Hb Vicksburg demonstrated a deletion of leucine at beta 75(E19), a new variant. Hb Vicksburg was neither unstable nor subject to posttranslational degradation. The alpha/non-alpha biosynthetic ratio was 2.6. Because the proband appeared to be a mixed heterozygote for Hb Vicksburg and beta 0-thalassemia, Hb Vicksburg should have comprised the major portion of the hemolysate. Thus, Hb Vicksburg was synthesized at a rate considerably lower than would be expected on the basis of gene dosage. There was no reason to suspect abnormal translation of beta Vicksburg mRNA; in individuals with Hb St. Antoine (beta 74 and beta 75 deleted), the abnormal hemoglobin comprised 25% of the hemolysate in the simple heterozygote yet was unstable. Deletion of beta 75, therefore, would not in itself appear to lead to diminished synthesis. There was a profound deficit of beta Vicksburg mRNA when measured by liquid hybridization analysis with beta cDNA. The most plausible explanation for the low output of Hb Vicksburg is that a mutation for beta +-thalassemia is present in cis to the structural mutation.

  3. Evaluation of cognition in children with beta-thalassemia major and healthy counterparts in terms of abstract thinking and visual organization

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    Samaneh Homayouni-Meymandi


    Conclusion: The results show the potential impact of the disease on children›s cognitive levels and suggest that children with beta-thalassemia major need more attention in the field of education to promote their understanding.

  4. A novel deletion in the thyrotropin Beta-subunit gene identified by array comparative genomic hybridization analysis causes central congenital hypothyroidism in a boy originating from Turkey. (United States)

    Hermanns, Pia; Couch, Robert; Leonard, Norma; Klotz, Cherise; Pohlenz, Joachim


    Isolated central congenital hypothyroidism (ICCH) is rare but important. Most ICCH patients are diagnosed later, which results in severe growth failure and intellectual disability. We describe a boy with ICCH due to a large homozygous TSHβ gene deletion. A 51-day-old male Turkish infant, whose parents were first cousins, was admitted for evaluation of prolonged jaundice. His clinical appearance was compatible with hypothyroidism. Venous thyrotropin (TSH) was undetectably low, with a subsequent low free T4 and a low free T3, suggestive of central hypothyroidism. Using different PCR protocols, we could not amplify both coding exons of the boy's TSHβ gene, which suggested a deletion. An array comparative genomic hybridization (aCGH) using specific probes around the TSHβ gene locus showed him to be homozygous for a 6-kb deletion spanning all exons and parts of the 5' untranslated region of the gene. Infants who are clinically suspected of having hypothyroidism should be evaluated thoroughly, even if their TSH-based screening result is normal. In cases with ICCH and undetectably low TSH serum concentrations, a TSHβ gene deletion should be considered; aCGH should be performed when gene deletions are suspected. In such cases, PCR-based sequencing techniques give negative results.

  5. Pituitary gland height evaluated by MR in patients with {beta}-thalassemia major: a marker of pituitary gland function

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    Argyropoulou, M.I.; Metafratzi, Z.; Efremidis, S.C. [Dept. of Radiology, Univ. of Ioannina (Greece); Kiortsis, D.N. [Dept. of Physiology, Univ. of Ioannina (Greece); Bitsis, S.; Tsatoulis, A. [Dept. of Internal Medicine, Univ. of Ioannina (Greece)


    In transfusion-dependent {beta}-thalassemia major, increased iron deposition in the pituitary gland has a cytotoxic effect leading mainly to hypogonadotropic hypogonadism. Our purpose was to assess in these patients the height of the pituitary gland and to evaluate whether it represents a marker of pituitary gland function. In 29 patients with {beta}-thalassemia major and 35 age- and gender-matched controls the pituitary gland height was evaluated in a midline sagittal scan using a spin echo T1-weighted (500/20 TR/TE) sequence. In all patients, an extensive endocrine evaluation was performed, including measurements of spontaneous and stimulated levels of gonadotropins, thyroid hormones, growth hormone, insulin-like growth factor, and adrenal hormones. The pituitary gland height was lower in thalassemic patients with hypogonadotropic hypogonadism (n=15) (mean 3.48; SD 0.46) than in the age- and gender-matched controls (mean 6.29; SD 0.77), (P<0.001). No statistically significant difference was found between thalassemic patients without hormone dysfunction (n=14) (mean 5.34; SD 1.52) and age- and gender-matched controls (mean 5.91; SD 1.06). We conclude that in thalassemic patients the pituitary gland height is an additional marker of pituitary gland function and might be useful in clinical management. (orig.)

  6. Orthodontic Consideration in Patients with Beta-Thalassemia Major: Case Report and Literature Review. (United States)

    Einy, Shmuel; Hazan-Molina, Hagai; Ben-Barak, Ayelet; Aizenbud, Dror

    Beta Thalassemia (βT) patients present a unique facial appearance and specific craniofacial, jaw and dental patterns. Although this anomaly often requires orthodontic management, βT patients have received scant attention in the orthodontic and dental literature over the past 50 years. The aim of this article is to review the characteristic craniofacial and dental manifestation pattern of βT patients and to emphasize their preferred orthodontic management protocol by presenting a βT orthodontic treated patient. A 10 year old patient presented with a complaint of severe esthetic and functional disorders due to her diagnosis of βT. We initiated orthodontic treatment including a combined orthopedic and functional treatment modality to improve facial appearance. Maxillary restraint and increased mandibular size during treatment along with an increase in the vertical dimension were achieved. The patient presented with Angle class I molar relationship, with reduction of the excessive overjet and deep overbite. Orthodontic treatment comprised of maxillary orthopedic treatment directed especially toward premaxilla with light forces, and mandibular modification by functional appliance along with fixed orthodontic treatment is recommended in βT patients.

  7. Assessment of cognitive function in children with beta-thalassemia major: a cross-sectional study. (United States)

    Raafat, Nelly; El Safy, Usama; Khater, Nahed; Hassan, Tamer; Hassan, Basheir; Siam, Ahmed; Youssef, Amira; El Shabrawy, Amany


    Multiple risk factors contribute to cognitive impairment in children with β-thalassemia major. For a more refined understanding of this issue, we attempted to evaluate cognitive function in β-thalassemia major patients and identify the relationship between possible cognitive dysfunction and the following: demography, transfusion and chelation characteristics, iron overload, and disease complications. We studied 100 β-thalassemia major children and 100 healthy controls who matched well in terms of age, sex, and socioeconomic status. All participants underwent psychometric assessment using Wechsler Intelligence Scale for Children-Third Edition, Arabic version. The mean Full-Scale IQ and Performance IQ of patients were significantly lower than those of controls, whereas no significant difference was found for Verbal IQ. No significant relationship existed between IQ and any of the assessed parameters. We concluded that Performance IQ, not Verbal IQ, was significantly affected in β-thalassemia major patients, but there was no clear association between IQ and any of the parameters. © The Author(s) 2014.

  8. Bone marrow changes in beta-thalassemia major: quantitative MR imaging findings and correlation with iron stores

    International Nuclear Information System (INIS)

    Drakonaki, Eleni E.; Karantanas, Apostolos H.; Maris, Thomas G.; Papadakis, Alex


    The purpose of this study is to describe the MR imaging features of bone marrow in beta-thalassemia major and investigate their relation to ferritin, liver and spleen siderosis. Spinal bone marrow was prospectively assessed on abdominal MR studies of 40 transfused beta-thalassemic patients and 15 controls using T1-w, Pd, T2*-w Gradient Echo (GRE) and T1-w turbo Spin Echo (TSE) sequences. Signal intensity (SI) ratios of liver, spleen and bone marrow to paraspinous muscles (L/M, S/M, B/M respectively) and the respective T2 relaxation rates (1/T2) were calculated. Serum ferritin levels were recorded. Bone marrow hypointensity in at least T2*-w GRE sequence was noted in 29/40 (72.5%) patients. Eleven/40 patients exhibited normal B/M on all MR sequences. Five/40 patients had normal B/M and low L/M. B/M correlated with L/M in T1-w TSE sequence only (r = 0.471, p = 0.05). B/M correlated with S/M and mean ferritin values in all sequences (r > 0.489, p - 0.496, p < 0.03 respectively). Marrow 1/T2 did not correlate with ferritin values or liver and spleen 1/T2. B/M in transfused beta-thalassemic patients is related to splenic siderosis and ferritin levels. Although marrow is usually hypointense, it may occasionally display normal SI coexisting with liver hypointensity, a pattern typical of primary hemochromatosis. (orig.)

  9. Bone marrow changes in beta-thalassemia major: quantitative MR imaging findings and correlation with iron stores

    Energy Technology Data Exchange (ETDEWEB)

    Drakonaki, Eleni E.; Karantanas, Apostolos H. [University Hospital of Heraklion, Radiology Department, Heraklion, Crete (Greece); Maris, Thomas G. [University of Crete, Department of Medical Physics, Heraklion, Crete (Greece); Papadakis, Alex [Venizelion General Hospital, Heraklion, Crete (Greece)


    The purpose of this study is to describe the MR imaging features of bone marrow in beta-thalassemia major and investigate their relation to ferritin, liver and spleen siderosis. Spinal bone marrow was prospectively assessed on abdominal MR studies of 40 transfused beta-thalassemic patients and 15 controls using T1-w, Pd, T2*-w Gradient Echo (GRE) and T1-w turbo Spin Echo (TSE) sequences. Signal intensity (SI) ratios of liver, spleen and bone marrow to paraspinous muscles (L/M, S/M, B/M respectively) and the respective T2 relaxation rates (1/T2) were calculated. Serum ferritin levels were recorded. Bone marrow hypointensity in at least T2*-w GRE sequence was noted in 29/40 (72.5%) patients. Eleven/40 patients exhibited normal B/M on all MR sequences. Five/40 patients had normal B/M and low L/M. B/M correlated with L/M in T1-w TSE sequence only (r = 0.471, p = 0.05). B/M correlated with S/M and mean ferritin values in all sequences (r > 0.489, p < 0.01 and r > - 0.496, p < 0.03 respectively). Marrow 1/T2 did not correlate with ferritin values or liver and spleen 1/T2. B/M in transfused beta-thalassemic patients is related to splenic siderosis and ferritin levels. Although marrow is usually hypointense, it may occasionally display normal SI coexisting with liver hypointensity, a pattern typical of primary hemochromatosis. (orig.)

  10. Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known Beta Thalassemia Major (United States)

    Soman, Salil; Rosenfeld, David L; Roychowdhury, Sudipta; Drachtman, Richard A; Cohler, Alan


    We describe a 16 year-old male with β thalassemia major and gait disturbances that had not been given blood transfusions due to a severe childhood transfusion reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the spine and epidural masses causing cord compression consistent with extramedullary hematopoiesis (EMH). After treatment with steroids, radiotherapy and monitored blood transfusions, the patient demonstrated significant improvement of his paraspinal lesions and near complete resolution of his neurological symptoms. While EMH causing cord compression in adolescents is rare in the current era of bone marrow transplantation or chronic transfusions, it should be considered when thalassemia major patients present with neurological deficits. The well defined imaging features of EMH can play a central role in its diagnosis and management, especially because surgical and / or radiotherapeutic intervention are often considered in cases of failed medical treatment. PMID:22470615

  11. Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known Beta Thalassemia Major

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    Alan COHLER


    Full Text Available We describe a 16 year-old male with ß thalassemia major and gait disturbances that had not been given blood transfusions due to a severe childhood transfusion reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the spine and epidural masses causing cord compression consistent with extramedullary hematopoiesis (EMH. After treatment with steroids, radiotherapy and monitored blood transfusions, the patient demonstrated significant improvement of his paraspinal lesions and near complete resolution of his neurological symptoms. While EMH causing cord compression in adolescents is rare in the current era of bone marrow transplantation or chronic transfusions, it should be considered when thalassemia major patients present with neurological deficits. The well defined imaging features of EMH can play a central role in its diagnosis and management, especially because surgical and / or radiotherapeutic intervention are often considered in cases of failed medical treatment.

  12. Cord Compression due to Extramedullary Hematopoiesis in an Adolescent with Known Beta Thalassemia Major


    Soman, Salil; Rosenfeld, David L; Roychowdhury, Sudipta; Drachtman, Richard A; Cohler, Alan


    We describe a 16 year-old male with ß thalassemia major and gait disturbances that had not been given blood transfusions due to a severe childhood transfusion reaction. Thoracic spine MRI demonstrated hematopoietic marrow throughout the spine and epidural masses causing cord compression consistent with extramedullary hematopoiesis (EMH). After treatment with steroids, radiotherapy and monitored blood transfusions, the patient demonstrated significant improvement of his paraspinal lesions a...

  13. Prevalence and Intensity of Depression in Mothers of Children with Beta-Thalassemia Major In Talghani Hospital of Gorgan, Iran

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    Nargesbeygom Mirbehbahani


    Full Text Available Background: Thalassemia is a chronic disease that it leads to psychological and social problems for parents. Mothers are at markedly increased risk of suffering from psychological distress and depression because they usually take on a considerable part of extra care that their children need.This study was designed to determine prevalence and intensity of depression in mothers with a thalassemic child. Material and Methods: In this cross – sectional study, 65 mothers of children with thalassemia major (case group and 65 mothers of children without thalassemia major (control group were assessed using the Beck Depression Inventory (BDI. Data were analyzed by using SPSS (v 16.0 for windows. Results: Prevalence of depression was significantly higher in case group than that in control group (84.6%vs. 56.9%, p <0.05. Moderate depression had a highest prevalence in the both groups (33.4% in case group and 30.8% in control group. Prevalence of severe depression in case group was markedly higher than that in control group (29.2% vs. 3.1% p<0.05. There was a significant difference between intensity of depression in mothers of case group that had another child with beta-thalassemia major (p<0.05. Conclusion: Mothers of children with thalassemia major are vulnerable to depression. They need psychosocial support to promote their health.

  14. Renal tubular dysfunction in pediatric patients with beta-thalassemia major

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    Ali Ahmadzadeh


    Full Text Available To evaluate the prevalence of renal tubular dysfunction in children with β-thalassemia (β-T major, we studied the glomerular and tubular function in 140 children with β-T major and compared them to a healthy control group at our center from May 2007 to April 2008. Fresh first morning samples were collected from each patient and analyzed for sodium, potassium, calcium (Ca, protein, uric acid (UA, creatinine (Cr, urine osmolality and urinary N-acetyl-β-D-glucosaminidase (UNAG activity. Blood samples were also collected for complete blood count, blood urea nitrogen (BUN, fasting blood sugar, serum creatinine (SCr, electrolytes, and ferritin before transfusion. Among the study patients, 72 were males, and the mean age was 11.5 (ranging 7-16 years. SCr levels were all within normal limits and all of them had normal glomerular filtration rate (GFR. The mean UNAG was 17.8 IU/L in the study patients (normal 0.15-11.5 IU/L and 3.2 IU/L in the control group (P 0.21 (P = 0.006. Nine (6.4% thalassemic patients with a mean age of 12 years had proteinuria (Upr/UCr > 0.2. Sixty-nine (49.3% out of the 140 patients and 45 (65.2% of the patients having UNAG had uricosuria also (UUA/UCr > 0.26. Ten (7% patients had microscopic hematuria and 10 (7% patients with a mean age of 13.5 years had glucosuria or diabetes mellitus. We conclude that tubular dysfunction is a relative common complication of the β-T major; UNAG and its index are the best to detect renal tubular dysfunction in these patients. Currently, periodic measurement of UCa/UCr and UUA/UCr ratios as well as urinalysis are recommended.

  15. Post-transfusion hypertension, convulsion and intracranial haemorrhage in beta-thalassemia major

    International Nuclear Information System (INIS)

    Masood, S.A.; Zaidi, A.


    The haematologic disorder b-thalassemia major is common in Pakistan. We describe a patient with undiagnosed thalassemia presenting with hypertension and convulsions and found to have cerebral haemorrhage on neuro-imaging. He had been transfused 2 weeks before this illness. Our experience is similar to a few case reports described in literature that were found to have cerebral haemorrhages post-mortem after a similar clinical presentation. All patients had a blood transfusion within 2 weeks prior to the presentation so association with transfusion has been proposed. We have reviewed the several mechanisms presented and discussed the findings. (author)

  16. Consanguinity Ratio in Beta-Thalassemia Major Patients in District Bannu

    International Nuclear Information System (INIS)

    Khan, M. S.; Ahmed, M.; Khan, R. A.; Mushtaq, N.; Shah, M. W. U.


    Objective: To assess the frequency of consanguinity in b-thalassemia major patients and its association with age, gender and hepatitis C virus antibody positivity. Methods: The cross-sectional study was conducted from June 2013 to July 2014 at various hospitals of district Bannu in the North Western Khyber Pakhtunkhwa province of Pakistan. Data was recorded on a predesigned questionnaire. Results: Out of 180 subjects, 133(74 percent) parents were cousins, while 47(26 percent) were unrelated. The frequency of anti-hepatitis C virus antibody positivity was 14(7.77 percent). Conclusion: High prevalence of the disease in the study region was due to consanguineous marriages. (author)

  17. Functional isotypes are not encoded by the constant region genes of the beta subunit of the T cell receptor for antigen/major histocompatibility complex



    Human T cell clones and a cDNA probe specific for constant regions of the beta subunit of the antigen/major histocompatibility complex (MHC) receptor, TiC beta 1 and TiC beta 2, were employed to determine whether these genes were differentially used by functional classes of T lymphocytes. DNA from 10 interleukin-2-dependent T cell clones including class I and class II MHC-specific cytotoxic T lymphocytes (n = 6), T4+ inducer T lymphocytes (n = 2), and T8+ suppressor T lymphocytes (n = 2) show...

  18. Hydroxyurea appears beneficial in patients with beta-thalassaemia major and intermedia

    Directory of Open Access Journals (Sweden)

    S. F.S.A. Abdul Wahid


    Full Text Available Patients with severe inherited β-globin chain disorders may have milder illness if they produce high levels of fetal hemoglobin (HbF. Hydroxyurea (HU has been shown to enhance HbF levels in patients with sickle cell disease and may be useful in β-thalassemias. We administered HU to 13 patients with β-thalassemia intermedia or major, including 6 splenectomized patients. The patients received escalating doses (10 to 25 mg/kg/d of HU for around 2 years (median: 21 months, range: 8 - 55 months. Eleven patients responded with an increase in the pre-transfusion HbF levels, from a base line median of 8.0% (2.5 - 61.3% to 28.0% (6.6 - 49.2% and 40.7% (4.8 - 72.3% at 3 months and 18 months post-HU, respectively. A concomitant increment in median hemoglobin levels was noted at 1, 3 and 18 months of HU therapy. Six of 7 transfusion-dependent patients who had an increment of HbF (one with β-thalassemia major also had reduced transfusion requirement over the 2-year period of HU therapy. Response to HU was also shown by a reduction in spleen size. Apart from oral ulcers that resolved upon dose reduction of HU, no significant toxicity was noted. We conclude that increased HbF production in β-thalassemia patients, with an improvement in erythropoiesis, can be achieved using HU with minimal toxicity. (Med J Indones 2007; 16:78-83 Keywords: fetal hemoglobin (HbF, erythropoiesis, toxicity

  19. Prevalence of hepatitis G virus in Pakistani children with transfusion dependent beta- thalassemia major. (United States)

    Moatter, T; Adil, S; Haroon, S; Azeemuddin, S; Hassan, F; Khurshid, M


    We ought to obtain data on the prevalence of the newly discovered tranfusion transmittable hepatitis G virus in polytransfused b- thalassemia major children. Each individual had received multiple blood transfusions, from 12 to 36 per year. No documentation of prior hepatic infection was available. Serum samples were collected prospectively from the randomly selected subjects and were analyzed for HGV RNA by polymerase chain reaction using primer specific for two different regions of the HGV genome. Among the 100 individuals examined 21 were positive for HGV RNA. Four patients had evidence of dual infection, both HGV RNA and HCV RNA were isolated from their sera. While in one sample presence of both HGV RNA and HBV DNA was established. Only one child was positive for hepatitis E antibodies. The sera of 10 children were reactive for hepatitis B surface antigen whereas 35 individuals were positive for hepatitis C virus antibody. The ALT levels were variable in HGV infected children. Four out of 16 (25%) showed peak ALT levels of 218 IU/I, 8/16 (50%) children demonstrated slightly elevated ALT levels whereas 25% individuals showed normal ALT levels. Alkaline Phosphatase levels were elevated in 90% of the children and 20% patients of this series also had higher GGT levels. The observed AP levels were not statistically different among HGV, HGV/HCV or HGV/HBV groups. Even though the ALT levels were deranged in the children with HGV alone but none of the children had demonstrated symptoms of liver disease, their direct and total bilirubin levels were normal and no complain of jaundice was recorded. In conclusion, our findings suggested that like other blood borne hepatic viruses, HGV is also prevalent in the high risk group of multiple transfused patients in Pakistan but our results support the absence of any causal relationship between HGV and hepatitis.

  20. The Correlation between Troponin and Ferritin Serum Levels in the Patients with Major Beta-Thalassemia

    Directory of Open Access Journals (Sweden)

    Iraj Shahramian


    Full Text Available Background: Thalassemia is a hereditary hemoglobinopathy whose most common complication is cardiac involvement which ends up in these patients’ death. Since troponin is a sensitive and specific marker for the detection of microinfarct, we studied the relationship between troponin and ferritin serum levels for early diagnosis of cardiac involvement in these patients. Materials and Methods: This case-control study was performed on 80 patients, including 40 patients with major thalassemia and normal echocardiography and 40 healthy volunteers ranging from 6 months to 16 years old. All the children were examined and the eligible children who were not infected with known heart disease, iron deficiency anemia, kidney disease, diabetes, fever, and systemic diseases were enrolled into the study after obtaining written informed consents from their parents. At 8:00 A.M. before breakfast, 5cc blood was drawn from these children. After collecting the samples, ferritin and troponin serum levels were evaluated using ELISA and electro- kymonolonsense methods, respectively. The gathered data were analyzed through the SPSS statistical software (v. 20 and T-test. Besides, P value<0.05 was considered as statistically significant. Results: The study results revealed a significant difference between the two groups regarding the mean of the serum levels of troponin (P=0.045 and ferritin (P=0.001. In this study, no significant correlation was observed between serum troponin and ferritin levels and age and BMI in the two groups. Also, no significant relationship was found between serum troponin level and sex (P=0.264. Conclusions: In microinfarct, troponin increases independent of ferritin; therefore, it can be used for early detection of cardiac involvement in thalassemia patients to determine the sub-clinical effects.

  1. Assessment of status of thyroid function in patients of beta thalassemia major, reporting to OPD of military hospital, rawalpindi

    International Nuclear Information System (INIS)

    Jehanzeb, K.


    Objective: To determine the status of thyroid functions in patients of Beta Thalassemia Major, reporting to OPD of Military Hospital, Rawalpindi. Study Design: Descriptive cross sectional study. Place and Duration of Study: Paediatric Outpatients Department of Military Hospital, Rawalpindi from 1st Jan to 30th Jun 2012. Material and Methods: After taking informed consent from the parents of all the children fulfilling the inclusion criteria, detailed history was taken and blood samples were drawn by strict aseptic means. Samples taken from these patients included complete blood and thyroid profile (serum thyroxine T4, triiodothyronine T3 and thyroid stimulating hormone TSH). These blood samples were labeled and sent to Armed Forces Institute of Pathology (AFIP), Rawalpindi for analysis by enzyme-linked immunosorbent assay (ELISA). Primary hypothyroidism was defined by TSH levels >4IU/ml. Statistical analysis was done at the end of study using SPSS version 10. Significance for association was calculated using student t-test. Results: Sixty patients fulfilled the inclusion criteria out of these sixty four patients lost the follow up while 56 patients completed the study. Out of 56 patients, 21 (37.5 percent) had biochemical evidence of hypothyroidism. Mean Ferritin level was 3924 +- 1247ng/ml in hypothyroid and 3136 +- 1387ng/ml in euthyroid patients indicating a significant difference in mean serum ferritin levels between hypothyroid patients and others. Conclusion: The study demonstrates hypothyroidism in a significant number of hyper transfused Beta- thalassemic patients, emphasizing the importance of monitoring thyroid functions in thalassemic patients, particularly in those receiving suboptimal chelation. (author)

  2. Dual energy x-ray absorptiometry (DEXA) in the assessment of liver iron in patients with beta thalassaemia major

    International Nuclear Information System (INIS)

    Chatterton, B.E.; Thomas, C.M.; Schultz, C.G.


    Full text: Beta thalassaemia major is a condition in which anaemia from abnormal haemoglobin production causes bone marrow expansion and frequently reduced bone mineral density. These patients have a chronic requirement for transfusion which results in tissue iron overload which may cause organ damage. Increased X-ray attenuation in the liver was noted in patients undergoing whole body DEXA for the assessment of bone density and it was assumed that this was related to liver iron stores. The aim of this study was to determine if useful information about liver iron could be obtained from these studies. Method: Using a Lunar DPXL, whole body scanning was performed in 16 patients (eight male) age 19-32 with Beta Thalassaemia. As well as calculating indices of total body composition, regions of interest were placed over the visualised liver. The 'bone mineral content' (BMC),g and bone mineral density (BMD),g/cm 2 were calculated over the liver regions, with the assumption that the calculation related to mineral in the region of interest. The results were compared with the serum ferritin as an indirect measure of body iron stores. Results showed a highly significant correlation (r=0.85) between 'BMD' in the liver region and ferritin. Conclusion: Despite the known difficulties with equating iron stores and ferritin, and possible confounders on liver density, such as fibrosis, the high correlation suggests that DEXA may have a place in the assessment of iron deposition, and be more cost effective than other technologies such as MRI and CT. Prospective studies with invasive measurements of liver iron will be needed to determine this. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  3. Beta-Thalassemia Major and Female Fertility: The Role of Iron and Iron-Induced Oxidative Stress (United States)

    Roussou, Paraskevi; Tsagarakis, Nikolaos J.; Diamanti-Kandarakis, Evanthia


    Endocrine complications due to haemosiderosis are present in a significant number of patients with beta-thalassemia major (BTM) worldwide and often become barriers in their desire for parenthood. Thus, although spontaneous fertility can occur, the majority of females with BTM is infertile due to hypogonadotropic hypogonadism (HH) and need assisted reproductive techniques. Infertility in these women seems to be attributed to iron deposition and iron-induced oxidative stress (OS) in various endocrine organs, such as hypothalamus, pituitary, and female reproductive system, but also through the iron effect on other organs, such as liver and pancreas, contributing to the impaired metabolism of hormones and serum antioxidants. Nevertheless, the gonadal function of these patients is usually intact and fertility is usually retrievable. Meanwhile, a significant prooxidants/antioxidants imbalance with subsequent increased (OS) exists in patients with BTM, which is mainly caused by tissue injury due to overproduction of free radicals by secondary iron overload, but also due to alteration in serum trace elements and antioxidant enzymes. Not only using the appropriate antioxidants, essential trace elements, and minerals, but also regulating the advanced glycation end products, could probably reduce the extent of oxidative damage and related complications and retrieve BTM women's infertility. PMID:24396593

  4. Cure of beta-thalassaemia major by umbilical cord blood transplantation--a case report of Malaysia's first cord blood transplantation. (United States)

    Chan, L L; Lin, H P


    A 25-month-old boy with beta-thalassaemia major was presented with an opportunity for umbilical cord blood transplantation when his unborn sibling was diagnosed in utero to be a beta-thalassaemia carrier and also human leucocyte antigen compatible. A barely adequate amount of cord blood was collected at the birth of his sibling and infused into the patient after appropriate chemo-conditioning. Engraftment occurred without major complications. The subject is now alive and well 9 months post-transplant, thus marking our first success in umbilical cord blood transplantation.

  5. Functional labeling of insulin receptor subunits in live cells. Alpha 2 beta 2 species is the major autophosphorylated form

    International Nuclear Information System (INIS)

    Le Marchand-Brustel, Y.; Ballotti, R.; Gremeaux, T.; Tanti, J.F.; Brandenburg, D.; Van Obberghen, E.


    Both receptor subunits were functionally labeled in order to provide methods allowing, in live cells and in broken cell systems, concomitant evaluation of the insulin receptor dual function, hormone binding, and kinase activity. In cell-free systems, insulin receptors were labeled on their alpha-subunit with 125I-photoreactive insulin, and on their beta-subunit by autophosphorylation. Thereafter, phosphorylated receptors were separated from the complete set of receptors by means of anti-phosphotyrosine antibodies. Using this approach, a subpopulation of receptors was found which had bound insulin, but which were not phosphorylated. Under nonreducing conditions, receptors appeared in three oligomeric species identified as alpha 2 beta 2, alpha 2 beta, and alpha 2. Mainly the alpha 2 beta 2 receptor species was found to be phosphorylated while insulin was bound to alpha 2 beta 2, alpha 2 beta, and alpha 2 forms. In live cells, biosynthetic labeling of insulin receptors was used. Receptors were first labeled with [35S]methionine. Subsequently, the addition of insulin led to receptor autophosphorylation by virtue of the endogenous ATP pool. The total amount of [35S]methionine-labeled receptors was precipitated with antireceptor antibodies, whereas with anti-phosphotyrosine antibodies, only the phosphorylated receptors were isolated. Using this approach we made the two following key findings: (1) Both receptor species, alpha 2 beta 2 and alpha 2 beta, are present in live cells and in comparable amounts. This indicates that the alpha 2 beta form is not a degradation product of the alpha 2 beta 2 form artificially generated during receptor preparation. (2) The alpha 2 beta 2 species is the prevalently autophosphorylated form

  6. CRISPR/Cas9-Mediated Genomic Deletion of the Beta-1, 4 N-acetylgalactosaminyltransferase 1 Gene in Murine P19 Embryonal Carcinoma Cells Results in Low Sensitivity to Botulinum Neurotoxin Type C.

    Directory of Open Access Journals (Sweden)

    Kentaro Tsukamoto

    Full Text Available Botulinum neurotoxins produced by Clostridium botulinum cause flaccid paralysis by inhibiting neurotransmitter release at peripheral nerve terminals. Previously, we found that neurons derived from the murine P19 embryonal carcinoma cell line exhibited high sensitivity to botulinum neurotoxin type C. In order to prove the utility of P19 cells for the study of the intracellular mechanism of botulinum neurotoxins, ganglioside-knockout neurons were generated by deletion of the gene encoding beta-1,4 N-acetylgalactosaminyltransferase 1 in P19 cells using the clustered regularly interspaced short palindromic repeats combined with Cas9 (CRISPR/Cas9 system. By using this system, knockout cells could be generated more easily than with previous methods. The sensitivity of the generated beta-1,4 N-acetylgalactosaminyltransferase 1-depleted P19 neurons to botulinum neurotoxin type C was decreased considerably, and the exogenous addition of the gangliosides GD1a, GD1b, and GT1b restored the susceptibility of P19 cells to botulinum neurotoxin type C. In particular, addition of a mixture of these three ganglioside more effectively recovered the sensitivity of knockout cells compared to independent addition of GD1a, GD1b, or GT1b. Consequently, the genome-edited P19 cells generated by the CRISPR/Cas9 system were useful for identifying and defining the intracellular molecules involved in the toxic action of botulinum neurotoxins.

  7. Beta-amyloid deposition in patients with major depressive disorder with differing levels of treatment resistance: a pilot study. (United States)

    Li, Peng; Hsiao, Ing-Tsung; Liu, Chia-Yih; Chen, Chia-Hsiang; Huang, She-Yao; Yen, Tzu-Chen; Wu, Kuan-Yi; Lin, Kun-Ju


    Lack of treatment response in patients with late-life depression is common. The role of brain beta-amyloid (Aβ) deposition in treatment outcome in subjects with late-life depression remains unclear. The present study aimed to investigate brain Aβ deposition in patients with major depressive disorder (MDD) with differing treatment outcomes in vivo using 18 F-florbetapir imaging. This study included 62 MDD patients and 18 healthy control subjects (HCs).We first employed the Maudsley staging method (MSM) to categorize MDD patients into two groups according to treatment response: mild treatment resistance (n = 29) and moderate-to-severe treatment resistance (n = 33).The standard uptake value ratio (SUVR) of each volume of interest was analysed, and voxel-wise comparisons were made between the MDD patients and HCs. Vascular risk factors, serum homocysteine level, and apolipoprotein E (ApoE) genotype were also determined. The MDD patients with moderate-to-severe treatment resistance had higher 18 F-florbetapir SUVRs than the HCs in the parietal region (P depressive symptoms may represent prodromal manifestations of Alzheimer's disease (AD). Depressive symptomatology in old age, particularly in subjects with a poor treatment response, may underscore early changes of AD-related pathophysiology.

  8. Molecular Modeling of the Major DNA Adduct Formed from Food Mutagen Ochratoxin A in NarI Two-Base Deletion Duplexes: Impact of Sequence Context and Adduct Ionization on Conformational Preference and Mutagenicity. (United States)

    Kathuria, Preetleen; Sharma, Purshotam; Manderville, Richard A; Wetmore, Stacey D


    Exposure to ochratoxin A (OTA), a possible human carcinogen, leads to many different DNA mutations. As a first step toward understanding the structural basis of OTA-induced mutagenicity, the present work uses a robust computational approach and a slipped mutagenic intermediate model previously studied for C 8 -dG aromatic amine adducts to analyze the conformational features of postreplication two-base deletion DNA duplexes containing OT-dG, the major OTA lesion at the C 8 position of guanine. Specifically, a total of 960 ns of molecular dynamics simulations (excluding trial simulations) were carried out on four OT-dG ionization states in three sequence contexts within oligomers containing the NarI recognition sequence, a known hotspot for deletion mutations induced by related adducts formed from known carcinogens. Our results indicate that the structural properties and relative stability of the competing "major groove" and "stacked" conformations of OTA adducted two-base deletion duplexes depend on both the OTA ionization state and the sequence context, mainly due to conformation-dependent deviations in discrete local (hydrogen-bonding and stacking) interactions at the lesion site, as well as DNA bending. When the structural characteristics of the OT-dG adducted two-base deletion duplexes are compared to those associated with previously studied C 8 -dG adducts, a greater understanding of the effects of the nucleobase-carcinogen linkage, and size of the carcinogenic moiety on the conformational preferences of damaged DNA is obtained. Most importantly, our work predicts key structural features for OT-dG-adducted deletion DNA duplexes, which in turn allow us to develop hypotheses regarding OT-dG replication outcomes. Thus, our computational results are valuable for the design and interpretation of future biochemical studies on the potentially carcinogenic OT-dG lesion.

  9. Distribution of serum lipids and lipoproteins in patients with beta thalassaemia major; an epidemiological study in young adults from Greece

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    Barbetseas John


    Full Text Available Abstract Background Beta-thalassaemia major (b-TM has been defined as a combination of chronic hemolytic anemia, iron storage disease and myocarditis, and it has been associated with premature death especially due to heart failure. To the best of our knowledge the status of blood lipids in these patients has rarely been investigated. Thus, we assessed the levels of lipids and lipoproteins in a sample of cardiovascular disease free adult men and women with b-TM. Methods During 2003 we enrolled 192 consecutive patients with b-TM that visited our Institution for routine examinations. The Institution is considered the major reference center for b-TM in Greece. Of the 192 patients, 88 were men (25 ± 6 years old and 104 women (26 ± 6 years old. Fasting blood lipid levels were measured in all participants. Results Data analysis revealed that 4% of men and 2% of women had total serum cholesterol levels > 200 mg/dl, and 11% of men and 17% of women had triglyceride levels > 150 mg/dl. In addition, mean HDL cholesterol levels were 32 ± 11 mg/dl in men and 38 ± 10 mg/dl in women, lipoprotein-a levels were 8.3 ± 9 mg/dl in men and 8.8 ± 9 mg/dl in women, apolipoprotein-A1 levels were 111 ± 17 mg/dl in men and 123 ± 29 mg/dl in women, and apolipoprotein-B levels were 60 ± 20 mg/dl in men and 59 ± 14 mg/dl in women. Total-to-HDL cholesterol ratios were 3.7 ± 1.2 and 3.8 ± 1.5 in men and women, respectively. Conclusions The majority of the patients had blood lipid levels (by the exception of HDL-cholesterol within the normal range, and consequently the prevalence of lipid and lipoprotein abnormalities was much lower as compared to the general population of the same age. Interestingly, is that the total – to HDL cholesterol ratio was high in our patients, and may underline the importance of this index for the prognosis of future cardiac events in these patients.

  10. Deletion of beta-2-microglobulin ameliorates spinal cord lesion load and promotes recovery of brainstem NAA levels in a murine model of multiple sclerosis. (United States)

    Denic, Aleksandar; Pirko, Istvan; Wootla, Bharath; Bieber, Allan; Macura, Slobodan; Rodriguez, Moses


    We used genetic deletion of β2-microglobulin to study the influence of CD8(+) T cells on spinal cord demyelination, remyelination, axonal loss and brainstem N-acetyl aspartate levels during the acute and chronic phases of Theiler's murine encephalomyelitis virus (TMEV) infection. We used β2m(-/-) and β2m(+/+) B10.Q mice (of H-2(q) background) normally susceptible to TMEV-induced demyelination. Over the disease course, β2m(+/+) mice had increasing levels of demyelination and minimal late-onset remyelination. In contrast, β2m(-/-) mice had steady levels of demyelination from 45-390 dpi and remyelination was extensive and more complete. Early in the disease, brainstem NAA levels drop in both strains, but accordingly with remyelination and axonal preservation, NAA recover in β2m(-/-) mice despite equivalent brainstem pathology. At 270 dpi, β2m(+/+) mice had significantly fewer spinal cord axons than β2m(-/-) mice (up to 28% less). In addition, β2m(+/+) mice lost axons of all calibers, whereas β2m(-/-) mice had a modest loss of only medium- and large-caliber axons. This study further supports the hypothesis that CD8(+) T cells are involved in demyelination, and axonal loss following Theiler's virus-induced demyelination. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

  11. Spatial Factors Play a Major Role as Determinants of Endemic Ground Beetle Beta Diversity of Madeira Island Laurisilva (United States)

    Boieiro, Mário; Carvalho, José C.; Cardoso, Pedro; Aguiar, Carlos A. S.; Rego, Carla; de Faria e Silva, Israel; Amorim, Isabel R.; Pereira, Fernando; Azevedo, Eduardo B.; Borges, Paulo A. V.; Serrano, Artur R. M.


    The development in recent years of new beta diversity analytical approaches highlighted valuable information on the different processes structuring ecological communities. A crucial development for the understanding of beta diversity patterns was also its differentiation in two components: species turnover and richness differences. In this study, we evaluate beta diversity patterns of ground beetles from 26 sites in Madeira Island distributed throughout Laurisilva – a relict forest restricted to the Macaronesian archipelagos. We assess how the two components of ground beetle beta diversity (βrepl – species turnover and βrich - species richness differences) relate with differences in climate, geography, landscape composition matrix, woody plant species richness and soil characteristics and the relative importance of the effects of these variables at different spatial scales. We sampled 1025 specimens from 31 species, most of which are endemic to Madeira Island. A spatially explicit analysis was used to evaluate the contribution of pure environmental, pure spatial and environmental spatially structured effects on variation in ground beetle species richness and composition. Variation partitioning showed that 31.9% of species turnover (βrepl) and 40.7% of species richness variation (βrich) could be explained by the environmental and spatial variables. However, different environmental variables controlled the two types of beta diversity: βrepl was influenced by climate, disturbance and soil organic matter content whilst βrich was controlled by altitude and slope. Furthermore, spatial variables, represented through Moran’s eigenvector maps, played a significant role in explaining both βrepl and βrich, suggesting that both dispersal ability and Madeira Island complex orography are crucial for the understanding of beta diversity patterns in this group of beetles. PMID:23724065

  12. Bauer-7-en-3{beta}-yl acetate: a major constituent of unusual samples of Brazilian propolis

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Erica Weinstein [Secretaria da Agricultura e Abastecimento, Pindamonhangaba, SP (Brazil). Agencia Paulista de Tecnologia dos Agronegocios; Message, Dejair [Vicosa Univ., MG (Brazil). Inst. de Biociencias. Dept. de Biologia Animal; Negri, Giuseppina; Salatino, Antonio [Sao Paulo Univ., SP (Brazil). Dept. de Botanica


    The pentacyclic triterpenoid bauer-7-en-3{beta}-yl acetate was obtained from thloroform extract of an unusual sample of propolis from southeast Brazil with the yield of 7%. The compound was identified by comparison of IR, MS and NMR analysis with published data. (author)

  13. Evaluation of heart disease in patients with beta-thalessemia major referred to Shahid Madanni Hospital in Khorram Abad in 2003

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    azam Mohsenzadeh


    Conclusions: Based on the X2 test, there was a postive correlation between age, age of Desferal use, and serum ferretin with cardiac disease (P<0.05. However, there was no correlation between age and blood group with cardiac disease. It is suggested that patients with beta-thalessemia major have blood transfusions and use Deseral regularly. Also, it is necessary to periodically evaluate the heart function of these patients.

  14. Relative stability of major types of beta-turns as a function of amino acid composition: a study based on Ab initio energetic and natural abundance data. (United States)

    Perczel, András; Jákli, Imre; McAllister, Michael A; Csizmadia, Imre G


    Folding properties of small globular proteins are determined by their amino acid sequence (primary structure). This holds both for local (secondary structure) and for global conformational features of linear polypeptides and proteins composed from natural amino acid derivatives. It thus provides the rational basis of structure prediction algorithms. The shortest secondary structure element, the beta-turn, most typically adopts either a type I or a type II form, depending on the amino acid composition. Herein we investigate the sequence-dependent folding stability of both major types of beta-turns using simple dipeptide models (-Xxx-Yyy-). Gas-phase ab initio properties of 16 carefully selected and suitably protected dipeptide models (for example Val-Ser, Ala-Gly, Ser-Ser) were studied. For each backbone fold most probable side-chain conformers were considered. Fully optimized 321G RHF molecular structures were employed in medium level [B3LYP/6-311++G(d,p)//RHF/3-21G] energy calculations to estimate relative populations of the different backbone conformers. Our results show that the preference for beta-turn forms as calculated by quantum mechanics and observed in Xray determined proteins correlates significantly.

  15. Associations between a health-promoting lifestyle and quality of life among adults with beta-thalassemia major. (United States)

    Maheri, Aghbabak; Sadeghi, Roya; Shojaeizadeh, Davoud; Tol, Azar; Yaseri, Mehdi; Ebrahimi, Mojtaba


    A health-promoting lifestyle (HPL) is a factor that affects the quality of life (QoL) in patients with beta-thalassemia (β-thalassemia). Due to the lack of studies of this issue, this study aimed to determine the association between HPL and QoL among adults with β-thalassemia. This cross-sectional (descriptive-analytic) study was conducted among 389 adult patients with β-thalassemia in Tehran, Iran. The research instrument included a questionnaire consisting of three parts: demographic items, the Short-Form Health Survey and the Health-Promoting Lifestyle Profile. The data were analyzed using SPSS version 23.0. The results were considered significant at the conventional pthalassemia; these four dimensions explained 37.9% of the variance in QoL. QoL and HPL were not at acceptable levels among patients with thalassemia. Therefore, educational interventions emphasizing spiritual growth, physical activity, and interpersonal relations are necessary for patients with thalassemia.

  16. Beta-thalassemia

    Directory of Open Access Journals (Sweden)

    Origa Raffaella


    , deletions in the beta globin gene on chromosome 11, leading to reduced (beta+ or absent (beta0 synthesis of the beta chains of hemoglobin (Hb. Transmission is autosomal recessive; however, dominant mutations have also been reported. Diagnosis of thalassemia is based on hematologic and molecular genetic testing. Differential diagnosis is usually straightforward but may include genetic sideroblastic anemias, congenital dyserythropoietic anemias, and other conditions with high levels of HbF (such as juvenile myelomonocytic leukemia and aplastic anemia. Genetic counseling is recommended and prenatal diagnosis may be offered. Treatment of thalassemia major includes regular RBC transfusions, iron chelation and management of secondary complications of iron overload. In some circumstances, spleen removal may be required. Bone marrow transplantation remains the only definitive cure currently available. Individuals with thalassemia intermedia may require splenectomy, folic acid supplementation, treatment of extramedullary erythropoietic masses and leg ulcers, prevention and therapy of thromboembolic events. Prognosis for individuals with beta-thalassemia has improved substantially in the last 20 years following recent medical advances in transfusion, iron chelation and bone marrow transplantation therapy. However, cardiac disease remains the main cause of death in patients with iron overload.

  17. A time-driven, activity-based costing methodology for determining the costs of red blood cell transfusion in patients with beta thalassaemia major. (United States)

    Burns, K E; Haysom, H E; Higgins, A M; Waters, N; Tahiri, R; Rushford, K; Dunstan, T; Saxby, K; Kaplan, Z; Chunilal, S; McQuilten, Z K; Wood, E M


    To describe the methodology to estimate the total cost of administration of a single unit of red blood cells (RBC) in adults with beta thalassaemia major in an Australian specialist haemoglobinopathy centre. Beta thalassaemia major is a genetic disorder of haemoglobin associated with multiple end-organ complications and typically requiring lifelong RBC transfusion therapy. New therapeutic agents are becoming available based on advances in understanding of the disorder and its consequences. Assessment of the true total cost of transfusion, incorporating both product and activity costs, is required in order to evaluate the benefits and costs of these new therapies. We describe the bottom-up, time-driven, activity-based costing methodology used to develop process maps to provide a step-by-step outline of the entire transfusion pathway. Detailed flowcharts for each process are described. Direct observations and timing of the process maps document all activities, resources, staff, equipment and consumables in detail. The analysis will include costs associated with performing these processes, including resources and consumables. Sensitivity analyses will be performed to determine the impact of different staffing levels, timings and probabilities associated with performing different tasks. Thirty-one process maps have been developed, with over 600 individual activities requiring multiple timings. These will be used for future detailed cost analyses. Detailed process maps using bottom-up, time-driven, activity-based costing for determining the cost of RBC transfusion in thalassaemia major have been developed. These could be adapted for wider use to understand and compare the costs and complexities of transfusion in other settings. © 2018 British Blood Transfusion Society.

  18. The entire β-globin gene cluster is deleted in a form of τδβ-thalassemia.

    NARCIS (Netherlands)

    E.R. Fearon; H.H.Jr. Kazazian; P.G. Waber (Pamela); J.I. Lee (Joseph); S.E. Antonarakis; S.H. Orkin (Stuart); E.F. Vanin; P.S. Henthorn; F.G. Grosveld (Frank); A.F. Scott; G.R. Buchanan


    textabstractWe have used restriction endonuclease mapping to study a deletion involving the beta-globin gene cluster in a Mexican-American family with gamma delta beta-thalassemia. Analysis of DNA polymorphisms demonstrated deletion of the beta-globin gene from the affected chromosome. Using a DNA

  19. Interstitial deletion of the short arm of chromosome 3. Fetal pathology and exclusion of the gene for beta-galactosidase-1 (GLB-1) from 3(p11----p14.2)

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Coerdt, W; Hahnemann, N


    A de novo interstitial deletion of the short arm of chromosome 3 was prenatally diagnosed in a male fetus, karyotype 46,XY,del(3)(pter----p14.2::p11----qter). The fetus had craniofacial dysmorphisms, a single transverse palmar crease, ulnar deviation in the wrists, cardiovascular anomalies...

  20. Preferrential rearrangement in normal rabbits of the 3' VHa allotype gene that is deleted in Alicia mutants; somatic hypermutation/conversion may play a major role in generating the heterogeneity of rabbit heavy chain variable region sequences. (United States)

    Allegrucci, M; Young-Cooper, G O; Alexander, C B; Newman, B A; Mage, R G


    The rabbit is unique in having well-defined allotypes in the variable region of the heavy chain. Products of the VHa locus, (with alleles a1, a2, and a3), account for the majority of the serum immunoglobulins. A small percentage of the serum immunoglobulins are a-negative. In 1986, Kelus and Weiss described a mutation that depressed the expression of the Ig VH a2 genes in an a1/a2 rabbit. From this animal the Alicia rabbit strain was developed and the mutation was termed ali. We previously showed, using Southern analysis and the transverse alternating field electrophoresis technique, that the difference between the ali rabbit and normal is a relatively small deletion including some of the most 3' VH genes. The most JH proximal 3' VH1 genes in DNA from normal rabbits of a1, a2 and a3 haplotypes encode a1, a2 and a3 molecules respectively, and it has been suggested that these genes are responsible for allelic inheritance of VHa allotypes. The present study suggests that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression in rabbits because VH gene(s) in this region are the target(s) of preferential VDJ rearrangements. This raises the possibility that mechanisms such as somatic gene conversion and hypermutation are at work to generate the antibody repertoire in this species. Our data support the view that the 3' VH1 gene may be the preferred target for rearrangement in normal rabbits, and for the normal chromosome in heterozygous ali animals. However, homozygous ali rabbits with a deletion that removed the a2-encoding VH1 on both chromosomes do survive, rearrange other VH genes and produce normal levels of immunoglobulins as well as a significant percentage of B cells which bear the a2 allotype. This challenges the view that one VH gene, VH1, is solely responsible for the inheritance pattern of VHa allotypes.

  1. Microglia and macrophages are major sources of locally produced transforming growth factor-beta1 after transient middle cerebral artery occlusion in rats

    DEFF Research Database (Denmark)

    Lehrmann, E; Kiefer, R; Christensen, Thomas


    The potentially neurotrophic cytokine transforming growth factor-beta1 (TGF-beta1) is locally expressed following human stroke and experimental ischemic lesions, but the cellular source(s) and profile of induction have so far not been established in experimental focal cerebral ischemia. This stud...

  2. Bone age estimation and prediction of final height in patients with {beta}-thalassaemia major: a comparison between the two most common methods

    Energy Technology Data Exchange (ETDEWEB)

    Christoforidis, Athanasios; Katzos, George; Athanassiou-Metaxa, Miranda [Aristotle University of Thessaloniki, 1st Paediatric Department, Thessaloniki (Greece); Badouraki, Maria [Ippokratio Hospital, Paediatric Radiology Department, Thessaloniki (Greece)


    Thalassaemic patients are in need of frequent assessment of bone age because of growth failure and pubertal disorders. To compare the ''rapid'' Greulich and Pyle (G and P) method with the third edition of the Tanner and Whitehouse (TW3) method for determining skeletal maturity and predicting final height in thalassaemic patients. A total of 191 radiographs from 58 patients (28 male, 30 female) were retrospectively evaluated by two investigators, one for each method. In 47 radiographs from 15 patients having attained their adult height, predicted final height was calculated according to each method. The mean bone ages determined by both the G and P and TW3 methods were lower than mean chronological age, although the differences were not statistically significant (10.04 {+-} 3.69 years and 9.98 {+-} 3.39 years vs. 10.78 {+-} 3.96 years, respectively). Both methods had a tendency to over-estimate final height. Overall, the TW3 method seemed to be more accurate than the G and P method (mean absolute error 3.21 {+-} 2.51 years vs. 3.99 {+-} 2.99 years, respectively, P=0.048). The same method should be used when serial assessments are performed, as both methods provide similarly reliable, although not equivalent, results. The TW3 height prediction method seemed to be more accurate in patients with {beta}-thalassaemia major than the G and P method, albeit with a large confidence interval. (orig.)

  3. Serotonin transporter binding with [{sup 123}I]{beta}-CIT SPECT in major depressive disorder versus controls: effect of season and gender

    Energy Technology Data Exchange (ETDEWEB)

    Ruhe, Henricus G. [University of Amsterdam, Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, Amsterdam (Netherlands); Academic Medical Center, Department of Psychiatry, P.O. Box 22660, Amsterdam (Netherlands); Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Reitsma, Johannes B. [University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam (Netherlands); Schene, Aart H. [University of Amsterdam, Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, Amsterdam (Netherlands)


    The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls. We included 49 depressed outpatients (mean{+-}SD 42.3 {+-} 8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for {>=}4 weeks, and 49 healthy controls matched for age ({+-}2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [{sup 123}I]{beta}-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BP{sub ND}) in the midbrain and diencephalon with cerebellar binding as a reference. In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosis x gender interaction; p = 0.048). In the diencephalon we found a comparable diagnosis x gender interaction (p = 0.002) and an additional smoking x gender (p = 0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p = 0.018) with higher SERT availability in winter. Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosis x gender and gender x smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD. (orig.)

  4. Fetzima (levomilnacipran), a drug for major depressive disorder as a dual inhibitor for human serotonin transporters and beta-site amyloid precursor protein cleaving enzyme-1. (United States)

    Rizvi, Syed Mohd Danish; Shaikh, Sibhghatulla; Khan, Mahiuddin; Biswas, Deboshree; Hameed, Nida; Shakil, Shazi


    Pharmacological management of Major Depressive Disorder includes the use of serotonin reuptake inhibitors which targets serotonin transporters (SERT) to increase the synaptic concentrations of serotonin. Beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1) is responsible for amyloid β plaque formation. Hence it is an interesting target for Alzheimer's disease (AD) therapy. This study describes molecular interactions of a new Food and Drug Administration approved antidepressant drug named 'Fetzima' with BACE-1 and SERT. Fetzima is chemically known as levomilnacipran. The study has explored a possible link between the treatment of Depression and AD. 'Autodock 4.2' was used for docking study. The free energy of binding (ΔG) values for 'levomilnacipran-SERT' interaction and 'levomilnacipran-BACE1' interaction were found to be -7.47 and -8.25 kcal/mol, respectively. Levomilnacipran was found to interact with S438, known to be the most important amino acid residue of serotonin binding site of SERT during 'levomilnacipran-SERT' interaction. In the case of 'levomilnacipran-BACE1' interaction, levomilnacipran interacted with two very crucial aspartic acid residues of BACE-1, namely, D32 and D228. These residues are accountable for the cleavage of amyloid precursor protein and the subsequent formation of amyloid β plaques in AD brain. Hence, Fetzima (levomilnacipran) might act as a potent dual inhibitor of SERT and BACE-1 and expected to form the basis of a future dual therapy against depression and AD. It is an established fact that development of AD is associated with Major Depressive Disorder. Therefore, the design of new BACE-1 inhibitors based on antidepressant drug scaffolds would be particularly beneficial.

  5. BETA digital beta radiometer

    International Nuclear Information System (INIS)

    Borovikov, N.V.; Kosinov, G.A.; Fedorov, Yu.N.


    Portable transportable digital beta radiometer providing for measuring beta-decay radionuclide specific activity in the range from 5x10 -9 up to 10 -6 Cu/kg (Cu/l) with error of ±25% is designed and introduced into commercial production for determination of volume and specific water and food radioactivity. The device specifications are given. Experience in the BETA radiometer application under conditions of the Chernobyl' NPP 30-km zone has shown that it is convenient for measuring specific activity of the order of 10 -8 Cu/kg, and application of a set of different beta detectors gives an opportunity to use it for surface contamination measurement in wide range of the measured value

  6. Partial deletion 11q

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Tommerup, N; Sørensen, F B


    We describe the cytogenetic findings and the dysmorphic features in a stillborn girl with a large de novo terminal deletion of the long arm of chromosome 11. The karyotype was 46,XX,del(11)(q21qter). By reviewing previous reports of deletion 11q, we found that cleft lip and palate are most...

  7. The Correlation of Cardiac and Hepatic Hemosiderosis as Measured by T2*MRI Technique with Ferritin Levels and Hemochromatosis Gene Mutations in Iranian Patients with Beta Thalassemia Major

    Directory of Open Access Journals (Sweden)

    Mohammad Soleiman Soltanpour


    Full Text Available Objectives: Organ-specific hemosiderosis and iron overload complications are more serious and more frequent in some patients with beta thalassemia major (BTM compared with others. We investigated whether coinheritance of HFE H63D or C282Y gene mutations in patients with BTM contributes to the phenotypic variation of iron overload complications and assessed the correlation of cardiac and hepatic hemosiderosis with plasma ferritin levels. Methods: We studied 60 patients with BTM with a mean age of 17.5±9.1 years from the Northwest of Iran. HFE gene mutations were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. Cardiac and hepatic hemosiderosis was assessed using T2*magnetic resonance imaging (MRI. Ferritin levels were measured using the enzyme immunoassay method. Results: Ferritin levels showed a strong inverse correlation with hepatic T2*MRI values (r = -0.631, p = 0.001 but a poor correlation with cardiac T2*MRI values (r = -0.297, p = 0.044. The correlation between cardiac T2*MRI values and hepatic T2*MRI values was poor and insignificant (r = 0.287, p = 0.058. Genotype and allele distribution of HFE H63D and C282Y mutation did not differ significantly between patients with and without hepatic or cardiac hemosiderosis (p > 0.050. However, carriers of HFE 63D allele had significantly higher ferritin levels compared with non-carriers (1 903±993 vs. 992±683, p < 0.001. Conclusions: Cardiac T2*MRI values showed a poor correlation with hepatic T2*MRI values and ferritin levels. Accurate assessment of cardiac iron overload in patients with BTM can only be done using the T2*MRI technique. Additionally, HFE H63D is a significant determinant factor for elevated ferritin levels in BTM patients.

  8. The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion processing in major depression. (United States)

    Baune, Bernhard T; Dannlowski, Udo; Domschke, Katharina; Janssen, Debbie G A; Jordan, Margaret A; Ohrmann, Patricia; Bauer, Jochen; Biros, Erik; Arolt, Volker; Kugel, Harald; Baxter, Alan G; Suslow, Thomas


    Accumulating evidence suggests the involvement of inflammatory processes and cytokines in particular in the pathophysiology of major depression (MDD) and resistance to antidepressant treatment. Furthermore, amygdala and anterior cingulate cortex (ACC) responsiveness to emotional stimuli has been suggested as a predictor of treatment response. This study investigated the association between genetic variants of the interleukin 1 beta (IL1B) gene and amygdala and ACC responsiveness to emotional stimuli and response to antidepressant treatment. In this analysis, 256 Caucasian patients with MDD (145 women, 111 men) were genotyped for variants rs16944, rs1143643, and rs1143634 in the IL1B gene (2q14). Response to antidepressant treatment over 6 weeks was defined as remission (50% decrease on Hamilton Rating Scale for Depression-21-question). Brain activity under visual presentation of emotional faces was assessed in a subsample of 32 depressed patients by means of functional magnetic resonance imaging at 3 T. Pharmacogenetic analyses show significant associations of the GG genotypes of single nucleotide polymorphisms (SNPs) rs16944 (odds ratio = 1.74; 95% confidence interval 1.2-4.3) and rs1143643 (odds ratio = 3.1; 95% confidence interval 1.3-7.8) (compared with the AA genotype) with nonremission after 6 weeks. The imaging analyses show that the number of G-alleles in both SNPs (rs16944 and rs1143643) was associated with reduced responsiveness of the amygdala and ACC to emotional stimulation. The present study suggests a negative effect of the IL1B gene on pharmacological response and amygdala and ACC function involving the same genotypes of two SNPs (rs16944, rs116343), which taken together increase the risk of nonremission over 6 weeks of antidepressant treatment in MDD. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Deletion mutations of bacteriophage

    International Nuclear Information System (INIS)

    Ryo, Yeikou


    Resolution of mutation mechanism with structural changes of DNA was discussed through the studies using bacteriophage lambda. One of deletion mutations inductions of phage lambda is the irradiation of ultraviolet ray. It is not clear if the inductions are caused by errors in reparation of ultraviolet-induced damage or by the activation of int gene. Because the effective site of int gene lies within the regions unnecessary for existing, it is considered that int gene is connected to deletion mutations induction. A certain system using prophage complementarity enables to detect deletion mutations at essential hereditary sites and to solve the relations of deletion mutations with other recombination system, DNA reproduction and repairment system. Duplication and multiplication of hereditary elements were discussed. If lambda deletion mutations of the system, which can control recombination, reproduction and repairment of added DNA, are constructed, mutations mechanism with great changes of DNA structure can be solved by phage lambda. (Ichikawa, K.)

  10. Schizophrenia and chromosomal deletions

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Baldini, A. [Baylor College of Medicine, Houston, TX (United States); Morris, M. A. [Univ. of Geneva School of Medicine, NY (United States)] [and others


    Recent genetic linkage analysis studies have suggested the presence of a schizophrenia locus on the chromosomal region 22q11-q13. Schizophrenia has also been frequently observed in patients affected with velo-cardio-facial syndrome (VCFS), a disorder frequently associated with deletions within 22q11.1. It has been hypothesized that psychosis in VCFS may be due to deletion of the catechol-o-methyl transferase gene. Prompted by these observations, we screened for 22q11 deletions in a population of 100 schizophrenics selected from the Maryland Epidemiological Sample. Our results show that there are schizophrenic patients carrying a deletion of 22q11.1 and a mild VCFS phenotype that might remain unrecognized. These findings should encourage a search for a schizophrenia-susceptibility gene within the deleted region and alert those in clinical practice to the possible presence of a mild VCFS phenotype associated with schizophrenia. 9 refs.

  11. Quantum deletion: Beyond the no-deletion principle

    International Nuclear Information System (INIS)

    Adhikari, Satyabrata


    Suppose we are given two identical copies of an unknown quantum state and we wish to delete one copy from among the given two copies. The quantum no-deletion principle restricts us from perfectly deleting a copy but it does not prohibit us from deleting a copy approximately. Here we construct two types of a 'universal quantum deletion machine' which approximately deletes a copy such that the fidelity of deletion does not depend on the input state. The two types of universal quantum deletion machines are (1) a conventional deletion machine described by one unitary operator and (2) a modified deletion machine described by two unitary operators. Here it is shown that the modified deletion machine deletes a qubit with fidelity 3/4, which is the maximum limit for deleting an unknown quantum state. In addition to this we also show that the modified deletion machine retains the qubit in the first mode with average fidelity 0.77 (approx.) which is slightly greater than the fidelity of measurement for two given identical states, showing how precisely one can determine its state [S. Massar and S. Popescu, Phys. Rev. Lett. 74, 1259 (1995)]. We also show that the deletion machine itself is input state independent, i.e., the information is not hidden in the deleting machine, and hence we can delete the information completely from the deletion machine

  12. Conditional deletion of Pten causes bronchiolar hyperplasia. (United States)

    Davé, Vrushank; Wert, Susan E; Tanner, Tiffany; Thitoff, Angela R; Loudy, Dave E; Whitsett, Jeffrey A


    Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that regulates multiple cellular processes including cell polarity, migration, proliferation, and carcinogenesis. In this work, we demonstrate that conditional deletion of Pten (Pten(Delta/Delta)) in the respiratory epithelial cells of the developing mouse lung caused epithelial cell proliferation and hyperplasia as early as 4 to 6 weeks of age. While bronchiolar cell differentiation was normal, as indicated by beta-tubulin and FOXJ1 expression in ciliated cells and by CCSP expression in nonciliated cells, cell proliferation (detected by expression of Ki-67, phospho-histone-H3, and cyclin D1) was increased and associated with activation of the AKT/mTOR survival pathway. Deletion of Pten caused papillary epithelial hyperplasia characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protruded into the airway lumens. Cell polarity, as assessed by subcellular localization of cadherin, beta-catenin, and zonula occludens-1, was unaltered. PTEN is required for regulation of epithelial cell proliferation in the lung and for the maintenance of the normal simple columnar epithelium characteristics of bronchi and bronchioles.

  13. Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. I. Recognition by two alpha beta T cell receptors

    DEFF Research Database (Denmark)

    Rognan, D; Stryhn, A; Fugger, L


    dynamics. Next, three-dimensional models of two different T cell receptors (TCRs) both specific for the Ha255-262/Kk complex were generated based on previously published TCR X-ray structures. Finally, guided by the recently published X-ray structures of ternary TCR/peptide/MHC-I complexes, the TCR models...... the models. They were found to account well for the experimentally obtained data, lending considerable support to the proposed models and suggesting a universal docking mode for alpha beta TCRs to MHC-peptide complexes. Such models may also be useful in guiding future rational experimentation....

  14. Rapid detection of pathological mutations and deletions of the haemoglobin beta gene (HBB) by High Resolution Melting (HRM) analysis and Gene Ratio Analysis Copy Enumeration PCR (GRACE-PCR). (United States)

    Turner, Andrew; Sasse, Jurgen; Varadi, Aniko


    Inherited disorders of haemoglobin are the world's most common genetic diseases, resulting in significant morbidity and mortality. The large number of mutations associated with the haemoglobin beta gene (HBB) makes gene scanning by High Resolution Melting (HRM) PCR an attractive diagnostic approach. However, existing HRM-PCR assays are not able to detect all common point mutations and have only a very limited ability to detect larger gene rearrangements. The aim of the current study was to develop a HBB assay, which can be used as a screening test in highly heterogeneous populations, for detection of both point mutations and larger gene rearrangements. The assay is based on a combination of conventional HRM-PCR and a novel Gene Ratio Analysis Copy Enumeration (GRACE) PCR method. HRM-PCR was extensively optimised, which included the use of an unlabelled probe and incorporation of universal bases into primers to prevent interference from common non-pathological polymorphisms. GRACE-PCR was employed to determine HBB gene copy numbers relative to a reference gene using melt curve analysis to detect rearrangements in the HBB gene. The performance of the assay was evaluated by analysing 410 samples. A total of 44 distinct pathological genotypes were detected. In comparison with reference methods, the assay has a sensitivity of 100 % and a specificity of 98 %. We have developed an assay that detects both point mutations and larger rearrangements of the HBB gene. This assay is quick, sensitive, specific and cost effective making it suitable as an initial screening test that can be used for highly heterogeneous cohorts.

  15. Different small, acid-soluble proteins of the alpha/beta type have interchangeable roles in the heat and UV radiation resistance of Bacillus subtilis spores

    International Nuclear Information System (INIS)

    Mason, J.M.; Setlow, P.


    Spores of Bacillus subtilis strains which carry deletion mutations in one gene (sspA) or two genes (sspA and sspB) which code for major alpha/beta-type small, acid-soluble spore proteins (SASP) are known to be much more sensitive to heat and UV radiation than wild-type spores. This heat- and UV-sensitive phenotype was cured completely or in part by introduction into these mutant strains of one or more copies of the sspA or sspB genes themselves; multiple copies of the B. subtilis sspD gene, which codes for a minor alpha/beta-type SASP; or multiple copies of the SASP-C gene, which codes for a major alpha/beta-type SASP of Bacillus megaterium. These findings suggest that alpha/beta-type SASP play interchangeable roles in the heat and UV radiation resistance of bacterial spores

  16. Speculative Betas


    Harrison Hong; David Sraer


    We provide a model for why high beta assets are more prone to speculative overpricing than low beta ones. When investors disagree about the common factor of cash-flows, high beta assets are more sensitive to this macro-disagreement and experience a greater divergence-of-opinion about their payoffs. Short-sales constraints for some investors such as retail mutual funds result in high beta assets being over-priced. When aggregate disagreement is low, expected return increases with beta due to r...

  17. Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial

    DEFF Research Database (Denmark)

    Juul, Anne Benedicte; Wetterslev, Jørn; Gluud, Christian


    Objectives To evaluate the long term effects of perioperative blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. Design Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. Setting University...

  18. Mechanism of the hydrolysis of 4-methylumbelliferyl-beta-D-glucoside by germinating and outgrowing spores of Bacillus species. (United States)

    Setlow, B; Cabrera-Martinez, R-M; Setlow, P


    during spore outgrowth in the presence of beta-MUG. Deletion of the genes coding for BglA, BglH, BglC and BglD reduced beta-MUG hydrolysis by germinating and outgrowing spores of B. subtilis 168 at least 99.7%. Assay of glucosidases active on beta-MUG or beta-MUG-P in extracts of dormant and outgrowing spores of B. atrophaeus revealed no enzyme active on beta-MUG and one enzyme that comprised > or =90% of the phosphoglucosidase active on beta-MUG-P. Partial purification and amino-terminal sequence analysis of this phosphoglucosidase identified this enzyme as BglH. Generation of MU from beta-MUG by germinating and outgrowing spores of B. atrophaeus and B. subtilis is mediated by the PTS-driven uptake and phosphorylation of beta-MUG, followed by phosphoglucosidase action on the intracellular beta-MUG-P. The major phosphoglucosidase catalyzing MU generation from beta-MUG-P in spores of both species is probably BglH. This work provides new insight into the mechanism of uptake and hydrolysis of beta-MUG by germinating and outgrowing spores of Bacillus species, in particular B. atrophaeus. The research reported here provides a biological basis for a Rapid Readout Biological Indicator that is used to monitor the efficacy of ethylene oxide sterilization.

  19. Distinct fates of self-specific T cells developing in irradiation bone marrow chimeras: Clonal deletion, clonal anergy, or in vitro responsiveness to self-Mls-1a controlled by hemopoietic cells in the thymus

    International Nuclear Information System (INIS)

    Speiser, D.E.; Chvatchko, Y.; Zinkernagel, R.M.; MacDonald, H.R.


    Elimination of potentially self-reactive T lymphocytes during their maturation in the thymus has been shown to be a major mechanism in accomplishing self-tolerance. Previous reports demonstrated that clonal deletion of self-Mls-1a-specific V beta 6+ T lymphocyte is controlled by a radiosensitive I-E+ thymic component. Irradiation chimeras reconstituted with I-E- bone marrow showed substantial numbers of mature V beta 6+ T cells despite host Mls-1a expression. Analysis of the functional properties of such chimeric T cells revealed a surprising variability in their in vitro reactivity to host Mls-1a, depending on the H-2 haplotype of stem cells used for reconstitution. In chimeras reconstituted with B10.S (H-2s) stem cells, mature V beta 6+ lymphocytes were present but functionally anergic to host-type Mls-1a in vitro. In contrast, in chimeras reconstituted with B10.G (H-2q) bone marrow, nondeleted V beta 6+ cells were highly responsive to Mls-1a in vitro. These findings suggest that clonal anergy of V beta 6+ cells to self-Mls-1a may be controlled by the affinity/avidity of T cell receptor interactions with bone marrow-derived cells in the thymus depending on the major histocompatibility complex class II molecules involved. Furthermore, chimeras bearing host (Mls-1a)-reactive V beta 6+ cells did not differ clinically from those with anergic or deleted V beta 6+ cells and survived more than one year without signs of autoimmune disease. Interestingly, their spleen cells had no Mls-1a stimulatory capacity in vitro. Therefore, regulation at the level of antigen presentation may be an alternative mechanism for maintenance of tolerance to certain self-antigens such as Mls-1a

  20. Beta spectrometry

    International Nuclear Information System (INIS)

    Dryak, P.; Zderadicka, J.; Plch, J.; Kokta, L.; Novotna, P.


    For the purpose of beta spectrometry, a semiconductor spectrometer with one Si(Li) detector cooled with liquid nitrogen was designed. Geometrical detection efficiency is about 10% 4 sr. The achieved resolution for 624 keV conversion electrons of sup(137m)Ba is 2.6 keV (FWHM). A program was written in the FORTRAN language for the correction of the deformation of the measured spectra by backscattering in the analysis of continuous beta spectra. The method permits the determination of the maximum energy of the beta spectrum with an accuracy of +-5 keV. (author)

  1. Reconstitution of normal and hyperactivated forms of casein kinase-2 by variably mutated beta-subunits

    DEFF Research Database (Denmark)

    Boldyreff, B; Meggio, F; Pinna, L A


    Twenty-one mutants of the noncatalytic beta-subunit of human casein kinase-2 have been created, expressed in Escherichia coli, and purified to homogeneity. They are either modified at the autophosphorylation site (mutants beta delta 1-4 and beta A 5,6) or bear variable deletions in their C...

  2. Beta Blockers (United States)

    ... may not work as effectively for people of African heritage and older people, especially when taken without ... conditions/high-blood-pressure/in-depth/beta-blockers/ART-20044522 . Mayo Clinic Footer Legal Conditions and Terms ...

  3. On Deletion of Sutra Translation

    Institute of Scientific and Technical Information of China (English)

    CHEN Shu-juan


    Dao An's the metaphor of translation "wine diluted with water' ' expressed a view about translation that had been abridged.Later Kumarajiva provided metaphor "rice chewed—tasteless and downright disgusting".Both of them felt regretted at the weakening of taste,sometimes even the complete loss of flavor caused by deletion in translation of Buddhist sutras.In early sutra translation,deletion is unavoidable which made many sutra translators felt confused and drove them to study it further and some even managed to give their understanding to this issue.This thesis will discuss the definition,and what causes deletion and the measures adopted by the sutra translators.

  4. Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M-type extended-spectrum beta-lactamases: a prospective study with Swedish volunteers. (United States)

    Tängdén, Thomas; Cars, Otto; Melhus, Asa; Löwdin, Elisabeth


    Foreign travel has been suggested to be a risk factor for the acquisition of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. To our knowledge, this has not previously been demonstrated in a prospective study. Healthy volunteers traveling outside Northern Europe were enrolled. Rectal swabs and data on potential travel-associated risk factors were collected before and after traveling. A total of 105 volunteers were enrolled. Four of them did not complete the study, and one participant carried ESBL-producing Escherichia coli before travel. Twenty-four of 100 participants with negative pretravel samples were colonized with ESBL-producing Escherichia coli after the trip. All strains produced CTX-M enzymes, mostly CTX-M-15, and some coproduced TEM or SHV enzymes. Coresistance to several antibiotic subclasses was common. Travel to India was associated with the highest risk for the acquisition of ESBLs (88%; n = 7). Gastroenteritis during the trip was an additional risk factor (P = 0.003). Five of 21 volunteers who completed the follow-up after 6 months had persistent colonization with ESBLs. This is the first prospective study demonstrating that international travel is a major risk factor for colonization with ESBL-producing Enterobacteriaceae. Considering the high acquisition rate of 24%, it is obvious that global efforts are needed to meet the emergence and spread of CTX-M enzymes and other antimicrobial resistances.

  5. Preventive Effects of Beta-Hydroxy-Beta-Methyl Butyrate


    N. Ravanbakhsh; N. Torabi; M. Foadoddini


    Aims: One of the major factors in sudden cardiac arrest is the initiation and continuation of deadly arrhythmias during ischemia. It is known that beta-hydroxy-beta-methylbutyrate (HMB) has useful effects such as anti-inflammatory and anti-apoptosis effects in the skeletal muscles. The aim of this study was to investigate the preventive effects of HMB on the ventricular arrhythmias due to the ischemia. Materials & Methods: In the experimental study, 30 Wistar male rats were randomly div...

  6. The chicken beta 2-microglobulin gene is located on a non-major histocompatibility complex microchromosome: a small, G+C-rich gene with X and Y boxes in the promoter

    DEFF Research Database (Denmark)

    Riegert, P; Andersen, R; Bumstead, N


    a similar genomic organization but smaller introns and higher G+C content than mammalian beta 2-microglobulin genes. The promoter region is particularly G+C-rich and contains, in addition to interferon regulatory elements, potential S/W, X, and Y boxes that were originally described for mammalian class II...... but not class I alpha or beta 2-microglobulin genes. There is a single chicken beta 2-microglobulin gene that has little polymorphism in the coding region. Restriction fragment length polymorphisms from Mhc homozygous lines, Mhc congenic lines, and backcross families, as well as in situ hybridization, show...

  7. Strategies for state-dependent quantum deleting

    International Nuclear Information System (INIS)

    Song Wei; Yang Ming; Cao Zhuoliang


    A quantum state-dependent quantum deleting machine is constructed. We obtain a upper bound of the global fidelity on N-to-M quantum deleting from a set of K non-orthogonal states. Quantum networks are constructed for the above state-dependent quantum deleting machine when K=2. Our deleting protocol only involves a unitary interaction among the initial copies, with no ancilla. We also present some analogies between quantum cloning and deleting

  8. ATLAS DQ2 Deletion Service

    International Nuclear Information System (INIS)

    Oleynik, Danila; Petrosyan, Artem; Garonne, Vincent; Campana, Simone


    The ATLAS Distributed Data Management project DQ2 is responsible for the replication, access and bookkeeping of ATLAS data across more than 100 distributed grid sites. It also enforces data management policies decided on by the collaboration and defined in the ATLAS computing model. The DQ2 Deletion Service is one of the most important DDM services. This distributed service interacts with 3rd party grid middleware and the DQ2 catalogues to serve data deletion requests on the grid. Furthermore, it also takes care of retry strategies, check-pointing transactions, load management and fault tolerance. In this paper special attention is paid to the technical details which are used to achieve the high performance of service, accomplished without overloading either site storage, catalogues or other DQ2 components. Special attention is also paid to the deletion monitoring service that allows operators a detailed view of the working system.

  9. Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells.

    Directory of Open Access Journals (Sweden)

    Moina Hasni Ebou

    Full Text Available Diabetes is a major complication of chronic Glucocorticoids (GCs treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1 and 2 (Tph2, leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells.

  10. Beta-amyloid deposition and cognitive function in patients with major depressive disorder with different subtypes of mild cognitive impairment: 18F-florbetapir (AV-45/Amyvid) PET study

    International Nuclear Information System (INIS)

    Wu, Kuan-Yi; Liu, Chia-Yih; Chen, Chia-Hsiang; Lee, Chin-Pang; Chen, Cheng-Sheng; Hsiao, Ing-Tsung; Hsieh, Chia-Ju; Yen, Tzu-Chen; Lin, Kun-Ju


    The objective of this study was to evaluate the amyloid burden, as assessed by 18 F-florbetapir (AV-45/Amyvid) positron emission tomography PET, in patients with major depressive disorder (MDD) with different subtypes of mild cognitive impairment (MCI) and the relationship between amyloid burden and cognition in MDD patients. The study included 55 MDD patients without dementia and 21 healthy control subjects (HCs) who were assessed using a comprehensive cognitive test battery and 18 F-florbetapir PET imaging. The standardized uptake value ratios (SUVR) in eight cortical regions using the whole cerebellum as reference region were determined and voxel-wise comparisons between the HC and MDD groups were performed. Vascular risk factors, serum homocysteine level and the apolipoprotein E (ApoE) genotype were also determined. Among the 55 MDD patients, 22 (40.0 %) had MCI, 12 (21.8 %) non-amnestic MCI (naMCI) and 10 (18.2 %) amnestic MCI (aMCI). The MDD patients with aMCI had the highest relative 18 F-florbetapir uptake in all cortical regions, and a significant difference in relative 18 F-florbetapir uptake was found in the parietal region as compared with that in naMCI subjects (P < 0.05) and HCs (P < 0.01). Voxel-wise analyses revealed significantly increased relative 18 F-florbetapir uptake in the MDD patients with aMCI and naMCI in the frontal, parietal, temporal and occipital areas (P < 0.005). The global cortical SUVR was significantly negatively correlated with MMSE score (r = -0.342, P = 0.010) and memory function (r = -0.328, P = 0.015). The negative correlation between the global SUVR and memory in the MDD patients remained significant in multiple regression analyses that included age, educational level, ApoE genotype, and depression severity (β = -3.607, t = -2.874, P = 0.006). We found preliminary evidence of brain beta-amyloid deposition in MDD patients with different subtypes of MCI. Our findings in MDD patients support the hypothesis that a higher

  11. Beta-amyloid deposition and cognitive function in patients with major depressive disorder with different subtypes of mild cognitive impairment: {sup 18}F-florbetapir (AV-45/Amyvid) PET study

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kuan-Yi; Liu, Chia-Yih; Chen, Chia-Hsiang; Lee, Chin-Pang [Chang Gung Memorial Hospital and Chang Gung University, Department of Psychiatry, Tao-Yuan (China); Chen, Cheng-Sheng [Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Department of Psychiatry, Kaohsiung (China); Hsiao, Ing-Tsung; Hsieh, Chia-Ju; Yen, Tzu-Chen; Lin, Kun-Ju [Chang Gung Memorial Hospital, Department of Nuclear Medicine and Molecular Imaging Center, Kuei Shan Hsiang, Taoyuan (China); Chang Gung University, Department of Medical Imaging and Radiological Sciences and Healthy Aging Research Center, Tao-Yuan (China)


    The objective of this study was to evaluate the amyloid burden, as assessed by {sup 18}F-florbetapir (AV-45/Amyvid) positron emission tomography PET, in patients with major depressive disorder (MDD) with different subtypes of mild cognitive impairment (MCI) and the relationship between amyloid burden and cognition in MDD patients. The study included 55 MDD patients without dementia and 21 healthy control subjects (HCs) who were assessed using a comprehensive cognitive test battery and {sup 18}F-florbetapir PET imaging. The standardized uptake value ratios (SUVR) in eight cortical regions using the whole cerebellum as reference region were determined and voxel-wise comparisons between the HC and MDD groups were performed. Vascular risk factors, serum homocysteine level and the apolipoprotein E (ApoE) genotype were also determined. Among the 55 MDD patients, 22 (40.0 %) had MCI, 12 (21.8 %) non-amnestic MCI (naMCI) and 10 (18.2 %) amnestic MCI (aMCI). The MDD patients with aMCI had the highest relative {sup 18}F-florbetapir uptake in all cortical regions, and a significant difference in relative {sup 18}F-florbetapir uptake was found in the parietal region as compared with that in naMCI subjects (P < 0.05) and HCs (P < 0.01). Voxel-wise analyses revealed significantly increased relative {sup 18}F-florbetapir uptake in the MDD patients with aMCI and naMCI in the frontal, parietal, temporal and occipital areas (P < 0.005). The global cortical SUVR was significantly negatively correlated with MMSE score (r = -0.342, P = 0.010) and memory function (r = -0.328, P = 0.015). The negative correlation between the global SUVR and memory in the MDD patients remained significant in multiple regression analyses that included age, educational level, ApoE genotype, and depression severity (β = -3.607, t = -2.874, P = 0.006). We found preliminary evidence of brain beta-amyloid deposition in MDD patients with different subtypes of MCI. Our findings in MDD patients support the

  12. A new alpha(0)-thalassemia deletion found in a Dutch family (--(AW)).

    NARCIS (Netherlands)

    Phylipsen, M.; Vogelaar, I.P.; Schaap, R.A.; Arkesteijn, S.G.; Boxma, G.L.; Helden, W.C. van; Wildschut, I.C.; Bruin-Roest, A.C. de; Giordano, P.C.; Harteveld, C.L.


    Alpha-thalassemia is an inherited hemoglobin disorder characterized by a microcytic hypochromic anemia caused by a quantitative reduction of the alpha-globin chain. The majority of the alpha-thalassemias is caused by deletions in the alpha-globin gene cluster. A deletion in the alpha-globin gene

  13. Enhanced expression in vivo of HLA-ABC antigens and beta 2-microglobulin on human lymphoid cells induced by human interferon-alpha in patients with lung cancer. Enhanced expression of class I major histocompatibility antigens prior to treatment

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Plesner, T; Larsen, J K


    than 0.5, respectively) by day-to-day analysis of an untreated healthy control group. An increased expression of both HLA-ABC (mean 55%, P less than 0.0005) and beta 2m (mean 23%, P less than 0.01) was also observed prior to treatment in the lung cancer patients when compared to a group of age matched......The effect of cloned human interferon-alpha (IFN-alpha) on the expression of HLA-ABC antigens (HLA-ABC) and beta 2-microglobulin (beta 2m) on human peripheral lymphoid cells in vivo was studied by cytofluorometry using monoclonal antibodies and fluorescein-labelled rabbit anti-mouse immunoglobulin....... A significant increase in the mean fluorescence intensity of HLA-ABC (median 59%, P less than 0.001) and beta 2m (median 57%, P less than 0.001) on small lymphoid cells was observed 24 h after initiation of IFN-alpha treatment (50 X 10(6) units IFN-alpha/m2 three times a week). The enhanced expression...

  14. Nature of mutants induced by ionizing radiation in cultured hamster cells. III. Molecular characterization of HPRT-deficient mutants induced by. gamma. -rays or. cap alpha. -particles showing that the majority have deletions of all or part of the hprt gene

    Energy Technology Data Exchange (ETDEWEB)

    Thacker, J


    DNA from 58 independent HPRT-deficient mutants of V79 hamster cells induced by ionizing radiation was analysed by Southern blot hybridization to a full-length hamster hprt cDNA. About half of the ..gamma..-ray-induced mutants (20/43) were apparently total gene deletions, because they lacked all functional hprt gene sequences hybridizing to the cDNA probe. Another 10 mutants showed various partial deletions and/or rearrangements of the hprt gene. The remaining 13 mutants showed no detectable change in comparison to the structure of the normal gene, which correlated well with previous characterization of these mutants indicating that most carry point mutations in the hprt gene. Thus, 70% or more of radiation-induced HPRT-deficient mutants arise through large genetic changes, especially deletions of all or part of the hprt gene. 16 references, 4 figures, 1 table.

  15. Beta Emission and Bremsstrahlung

    Energy Technology Data Exchange (ETDEWEB)

    Karpius, Peter Joseph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    Bremsstrahlung is continuous radiation produced by beta particles decelerating in matter; different beta emitters have different endpoint energies; high-energy betas interacting with high-Z materials will more likely produce bremsstrahlung; depending on the data, sometimes all you can say is that a beta emitter is present.

  16. Marcadores eletrocardiográficos para detecção precoce de doença cardíaca em pacientes com talassemia beta maior Electrocardiographic markers for the early detection of cardiac disease in patients with beta-thalassemia major

    Directory of Open Access Journals (Sweden)

    Kemal Nisli


    Full Text Available OBJETIVO: Analisar comparativamente a dispersão da onda P (DOP em pacientes com talassemia beta maior (β-TM e indivíduos saudáveis (controles para a detecção precoce do risco de arritmias. MÉTODOS: Oitenta e uma crianças com β-TM, com idades entre 4 e 19 anos, e 74 crianças saudáveis (grupo controle foram submetidas a exame eletrocardiográfico e ecocardiograma transtorácico de rotina para avaliação cardíaca. A DOP foi calculada como a diferença entre as durações máxima e mínima da onda P. RESULTADOS: Houve uma diferença estatisticamente significativa entre o grupo de estudo e o grupo controle no pico de velocidade do fluxo transmitral no início da diástole (E e na razão E/fluxo transmitral tardio (A. A duração máxima da onda P e a DOP foram significativamente maiores nos pacientes com β-TM do que nos indivíduos controles. CONCLUSÕES: O aumento da DOP em nossos pacientes com β-TM pode estar relacionado à depressão na condução intra-atrial, devido à dilatação atrial, e ao aumento da atividade simpática. Estes pacientes devem ser acompanhados atentamente devido à possibilidade de ocorrência de arritmias com risco de vida.OBJECTIVE: To comparatively evaluate P-wave dispersion (PWD in patients with β-thalassemia major (TM and healthy control subjects for the early prediction of arrhythmia risk. METHODS: Eighty-one children with β-TM, aged 4-19 years, and 74 healthy children (control group underwent routine electrocardiography and transthoracic echocardiography for cardiac evaluation. PWD was calculated as the difference between the maximum and the minimum P-wave duration. RESULTS: There was a statistically significant difference between study and control groups in peak early (E mitral inflow velocity and E/late (A velocity ratio. Maximum P-wave duration and PWD were found to be significantly higher in β-TM patients than in control subjects. CONCLUSIONS: Increased PWD in our β-TM patients might be related

  17. Interactions between beta subunits of the KCNMB family and Slo3: beta4 selectively modulates Slo3 expression and function.

    Directory of Open Access Journals (Sweden)

    Cheng-Tao Yang


    Full Text Available The pH and voltage-regulated Slo3 K(+ channel, a homologue of the Ca(2+- and voltage-regulated Slo1 K(+ channel, is thought to be primarily expressed in sperm, but the properties of Slo3 studied in heterologous systems differ somewhat from the native sperm KSper pH-regulated current. There is the possibility that critical partners that regulate Slo3 function remain unidentified. The extensive amino acid identity between Slo3 and Slo1 suggests that auxiliary beta subunits regulating Slo1 channels might coassemble with and modulate Slo3 channels. Four distinct beta subunits composing the KCNMB family are known to regulate the function and expression of Slo1 Channels.To examine the ability of the KCNMB family of auxiliary beta subunits to regulate Slo3 function, we co-expressed Slo3 and each beta subunit in heterologous expression systems and investigated the functional consequences by electrophysiological and biochemical analyses. The beta4 subunit produced an 8-10 fold enhancement of Slo3 current expression in Xenopus oocytes and a similar enhancement of Slo3 surface expression as monitored by YFP-tagged Slo3 or biotin labeled Slo3. Neither beta1, beta2, nor beta3 mimicked the ability of beta4 to increase surface expression, although biochemical tests suggested that all four beta subunits are competent to coassemble with Slo3. Fluorescence microscopy from beta4 KO mice, in which an eGFP tag replaced the deleted exon, revealed that beta4 gene promoter is active in spermatocytes. Furthermore, quantitative RT-PCR demonstrated that beta4 and Slo3 exhibit comparable mRNA abundance in both testes and sperm.These results argue that, for native mouse Slo3 channels, the beta4 subunit must be considered as a potential interaction partner and, furthermore, that KCNMB subunits may have functions unrelated to regulation of the Slo1 alpha subunit.

  18. Induction of beta-lactamase production in Pseudomonas aeruginosa biofilm

    DEFF Research Database (Denmark)

    Giwercman, B; Jensen, E T; Høiby, N


    Imipenem induced high levels of beta-lactamase production in Pseudomonas aeruginosa biofilms. Piperacillin also induced beta-lactamase production in these biofilms but to a lesser degree. The combination of beta-lactamase production with other protective properties of the biofilm mode of growth c...... could be a major reason for the persistence of this sessile bacterium in chronic infections....

  19. Physical mapping of chromosome 8p22 markers and their homozygous deletion in a metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bova, G.S.; Pin, S.S.; Isaacs, W.B. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)]|[Brady Urological Institute, Baltimore, MD (United States)] [and others


    Numerous studies have implicated the short arm of chromosome 8 as the site of one or more tumor suppressor genes inactivated in carcinogenesis of the prostate, colon, lung, and liver. Previously, we identified a homozygous deletion on chromosome 8p22 in a metastatic prostate cancer. To map this homozygous deletion physically, long-range restriction mapping was performed using yeast artificial chromosomes (YACs) spanning approximately 2 Mb of chromosome band 8p22. Subcloned genomic DNA and cDNA probes isolated by hybrid capture from these YACs were mapped in relation to one another, reinforcing map integrity. Mapped single-copy probes from the region were then applied to DNA isolated from a metastatic prostate cancer containing a chromosome 8p22 homozygous deletion and indicated that its deletion spans 730-970 kb. Candidate genes PRLTS (PDGF-receptor {beta}-like tumor suppressor) and CTSB (cathepsin B) are located outside the region of homozygous deletion. Genethon marker D8S549 is located approximately at the center of this region of homozygous deletion. Two new microsatellite polymorphisms, D8S1991 and D8S1992, also located within the region of homozygous deletion on chromosome 8p22, are described. Physical mapping places cosmid CI8-2644 telomeric to MSR (macrophage scavenger receptor), the reverse of a previously published map, altering the interpretation of published deletion studies. This work should prove helpful in the identification of candidate tumor suppressor genes in this region. 47 refs., 5 figs., 1 tab.

  20. Clonal deletion: A mechanism of tolerance in mixed bone marrow chimeras

    International Nuclear Information System (INIS)

    Yu, J.C.; Webster, M.; Fox, I.J.


    The mechanism of antigen-specific immunologic unresponsiveness which results from lethal irradiation and mixed (syngeneic-allogeneic) bone marrow cell (BMC) reconstitution is unknown. To determine whether clonal deletion is the mechanism of tolerance in this model, monoclonal antibody (Mab) RR-4-4, specific for a T-cell receptor (V beta 6) reactive against the minor alloantigen MLsa, was employed. Six-week-old B10 mice (H-2b, Mlsb, Thyl.2) were tolerized to AKR antigens (H-2k, Mlsa, Thyl.1) by whole body irradiation (950 R) and iv infusion of T-cell-depleted (TCD) B10 BMC + non-TCD AKR BMC. Chimerism and antigen-specific tolerance were documented by flow microfluorometry (FMF), skin grafting, mixed lymphocyte reaction, and cell-mediated lympholysis. When tolerant B10 mice (n = 15) had accepted AKR skin grafts for greater than 100 days, these animals were studied for the presence of host V beta 6+ T cells using Mab RR-4-4. FMF revealed that 0-5% of host (B10) lymph node and spleen cells from chimeras were V beta 6+ while 15-20% of lymph node and spleen cells from control B10 mice expressed V beta 6. These data demonstrate that clonal deletion occurs in the lethal irradiation-mixed reconstitution model as evidenced by the near total elimination of Mlsa-reactive V beta 6+ T cells and suggest that it maybe a mechanism responsible for tolerance in adult mice

  1. Generating Bona Fide Mammalian Prions with Internal Deletions. (United States)

    Munoz-Montesino, Carola; Sizun, Christina; Moudjou, Mohammed; Herzog, Laetitia; Reine, Fabienne; Chapuis, Jérôme; Ciric, Danica; Igel-Egalon, Angelique; Laude, Hubert; Béringue, Vincent; Rezaei, Human; Dron, Michel


    Mammalian prions are PrP proteins with altered structures causing transmissible fatal neurodegenerative diseases. They are self-perpetuating through formation of beta-sheet-rich assemblies that seed conformational change of cellular PrP. Pathological PrP usually forms an insoluble protease-resistant core exhibiting beta-sheet structures but no more alpha-helical content, loosing the three alpha-helices contained in the correctly folded PrP. The lack of a high-resolution prion structure makes it difficult to understand the dynamics of conversion and to identify elements of the protein involved in this process. To determine whether completeness of residues within the protease-resistant domain is required for prions, we performed serial deletions in the helix H2 C terminus of ovine PrP, since this region has previously shown some tolerance to sequence changes without preventing prion replication. Deletions of either four or five residues essentially preserved the overall PrP structure and mutant PrP expressed in RK13 cells were efficiently converted into bona fide prions upon challenge by three different prion strains. Remarkably, deletions in PrP facilitated the replication of two strains that otherwise do not replicate in this cellular context. Prions with internal deletion were self-propagating and de novo infectious for naive homologous and wild-type PrP-expressing cells. Moreover, they caused transmissible spongiform encephalopathies in mice, with similar biochemical signatures and neuropathologies other than the original strains. Prion convertibility and transfer of strain-specific information are thus preserved despite shortening of an alpha-helix in PrP and removal of residues within prions. These findings provide new insights into sequence/structure/infectivity relationship for prions. Prions are misfolded PrP proteins that convert the normal protein into a replicate of their own abnormal form. They are responsible for invariably fatal neurodegenerative

  2. A single-chain fusion molecule consisting of peptide, major histocompatibility gene complex class I heavy chain and beta2-microglobulin can fold partially correctly, but binds peptide inefficiently

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C; Buus, S


    of a recombinant murine MHC-I molecule, which could be produced in large amounts in bacteria. The recombinant MHC-I protein was expressed as a single molecule (PepSc) consisting of the antigenic peptide linked to the MHC-I heavy chain and further linked to human beta2-microglobulin (hbeta2m). The PepSc molecule...... electrophoresis (SDS-PAGE). Serological analysis revealed the presence of some, but not all, MHC-I-specific epitopes. Biochemically, PepSc could bind peptide, however, rather ineffectively. We suggest that a partially correctly refolded MHC-I has been obtained....

  3. Milk Intolerance, Beta-Casein and Lactose. (United States)

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen


    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows' milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows' milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows' milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  4. Milk Intolerance, Beta-Casein and Lactose

    Directory of Open Access Journals (Sweden)

    Sebely Pal


    Full Text Available True lactose intolerance (symptoms stemming from lactose malabsorption is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows’ milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  5. Levered and unlevered Beta


    Fernandez, Pablo


    We prove that in a world without leverage cost the relationship between the levered beta ( L) and the unlevered beta ( u) is the No-costs-of-leverage formula: L = u + ( u - d) D (1 - T) / E. We also analyze 6 alternative valuation theories proposed in the literature to estimate the relationship between the levered beta and the unlevered beta (Harris and Pringle (1985), Modigliani and Miller (1963), Damodaran (1994), Myers (1974), Miles and Ezzell (1980), and practitioners) and prove that all ...

  6. Beta Thalassemia (For Parents) (United States)

    ... Safe Videos for Educators Search English Español Beta Thalassemia KidsHealth / For Parents / Beta Thalassemia What's in this ... Symptoms Diagnosis Treatment Print en español Beta talasemia Thalassemias Thalassemias are a group of blood disorders that ...

  7. Probabilistic cloning and deleting of quantum states

    International Nuclear Information System (INIS)

    Feng Yuan; Zhang Shengyu; Ying Mingsheng


    We construct a probabilistic cloning and deleting machine which, taking several copies of an input quantum state, can output a linear superposition of multiple cloning and deleting states. Since the machine can perform cloning and deleting in a single unitary evolution, the probabilistic cloning and other cloning machines proposed in the previous literature can be thought of as special cases of our machine. A sufficient and necessary condition for successful cloning and deleting is presented, and it requires that the copies of an arbitrarily presumed number of the input states are linearly independent. This simply generalizes some results for cloning. We also derive an upper bound for the success probability of the cloning and deleting machine

  8. Spontaneous and mutagen-induced deletions: mechanistic studies in Salmonella tester strain TA102

    International Nuclear Information System (INIS)

    Levin, D.E.; Marnett, L.J.; Ames, B.N.


    Salmonella tester strain TA102 carries the hisG428 ochre mutation on the multicopy plasmid pAQ1. DNA sequence analysis of 45 spontaneous revertants of hisG428 on the chromosome in the presence of pKM101 (strain TA103) indicates that hisG428 revertants fall into three major categories: (i) small, in-frame deletions (3 or 6 base pairs) that remove part or all of the ochre triplet; (ii) base substitution mutations at the ochre site; (iii) extragenic ochre suppressors. Deletion revertants are identified in a simple phenotypic screen by their resistance to the inhibitory histidine analog thiazolealanine, which feedback inhibits the wild-type hisG enzyme but not the enzyme resulting from the deletions. The effect of various genetic backgrounds on the generation of spontaneous deletion revertants was examined. The presence of a uvrB mutation or a recA mutation suppressed the generation of spontaneous deletion revertants to approximately 1/2.5. When hisG428 was in multiple copies on pAQ1, the frequency of spontaneous deletion revertants increased by 40-fold, which is the approximate copy number of pAQ1. Mutagenic agents that induce single-strand breaks in DNA (e.g., x-rays, bleomycin, and nalidixic acid) induced deletion revertants in TA102. These agents induced deletion revertants only in hisG428 on pAQ1 and only in the presence of pKM101. Deletion revertants were not induced by frameshift mutagens (i.e., ICR-191 and 9aminoacridine). These results indicate that different pathways exist for the generation of spontaneous and mutagen-induced deletion revertants of hisG428. 41 references, 2 figures, 3 tables

  9. [Prevalence survey and molecular characterization of alpha and beta thalassemia in Liuzhou city of Guangxi]. (United States)

    Cai, Ren; Li, Liyan; Liang, Xin; Liu, Zhongying; Su, Liu; Li, Wenjun; Zhu, Qiangui; Mo, Qiuhua; Pan, Lizhen; Ouyang, Hong; Huang, Lihua; Xu, Xiangmin


    To investigate the gene frequencies and mutation patterns of alpha thalassemia (alpha-thal) and beta thalassemia (beta-thal) in Liuzhou city of Guangxi Zhuang Autonomous Region. Cluster sampling was used. A total of 1 028 of umbilical blood samples were collected for a prevalence study of alpha-thal and a total of 1 312 healthy young people when receiving pre-marriage consultation were recruited for a beta-thal prevalence survey. Individuals live in city or town area of Liuzhou. A complete blood count as well as hemoglobin electrophoresis analysis were done in all of samples for phenotyping of alpha and beta-thals. Those with Hb Bart's for alpha-thal indicator and those with both microcytosis (MCV /=4.0%) for beta-thal were further studied by DNA analysis. PCR-based methodologies were used to characterize the mutation contributions of alpha and beta-thals. All the subjects were tested for the state of carrying beta-thala alleles for evaluating the situation of the compound heterozygotes of alpha-thal with beta-thal. Of 1 028 random samples of umbilical blood screened, 112 of subjects were defined to be the gene carriers of alpha-thal. The alpha-thal carrier rate was as high as 11.19% including 3 compound heterozygotes. Five well-known types of alpha-thal alleles were detected with gene contributions of 37.4% (--(SEA) deletion), 31.3% (-alpha(3.7) deletion), 17.4% (-alpha(4.2) deletion), 12.1% (alpha(CS)alpha mutation), and 0.9% (alpha(QS)alpha mutation), successively. Of the 1 312 adult specimens studied, 89 with beta-thal including 14 of the compound higher Hb F subjects were detected. All of the 89 phenotypic beta-thal carriers had the mutations in the beta-globin gene, making the overall prevalence 6.78%. The commonly seen three mutations, beta CD41 - 42 (-CTTT) frameshift, beta CD17 (T-A) nonsense mutation and beta-28 (A-G) promoter variation were accounted for 90% of the beta-thal alleles in Liuzhou. Of these beta-thal subjects, 16 (accounting for 18%) were

  10. Forward-Looking Betas

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Vainberg, Gregory

    Few issues are more important for finance practice than the computation of market betas. Existing approaches compute market betas using historical data. While these approaches differ in terms of statistical sophistication and the modeling of the time-variation in the betas, they are all backward......-looking. This paper introduces a radically different approach to estimating market betas. Using the tools in Bakshi and Madan (2000) and Bakshi, Kapadia and Madan (2003) we employ the information embedded in the prices of individual stock options and index options to compute our forward-looking market beta...

  11. Two novel deletions (array CGH findings) in pigment dispersion syndrome. (United States)

    Mikelsaar, Ruth; Molder, Harras; Bartsch, Oliver; Punab, Margus


    We report the first male with pigment dispersion syndrome and a balanced translocation t(10;15)(p11.1;q11.1). Cytogenetic analyses using Giemsa banding and FISH methods, and array CGH were performed. Array CGH analyses did not show altered DNA sequences in the breakpoints of the translocation, but revealed two novel deletions in 2q22.1 and 18q22.1. We suppose that the coexistence of t(10;15) and pigment dispersion syndrome in our patient is a coincidence. The deletion in 2q22.1, where the gene LRP1B has been located, may play a major role in the dysembryogenesis of the eye and cause the disorder.

  12. Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. II. Cross-reaction between a monoclonal antibody and two alpha beta T cell receptors

    DEFF Research Database (Denmark)

    Rognan, D; Engberg, J; Stryhn, A


    -peptide pair into the Fab combining site. Interestingly, the most energetically favored binding mode shows numerous analogies to the recently determined recognition of class I MHC-peptide complexes by alpha beta T cell receptors (TCRs). The pSAN13.4.1 also binds diagonally across the MHC binding groove......The recombinant antibody, pSAN13.4.1, has a unique T cell like specificity; it binds an Influenza Hemagglutinin octapeptide (Ha255-262) in an MHC (H-2Kk)-restricted manner, and a detailed comparison of the fine specificity of pSAN13.4.1 with the fine specificity of two Ha255-262-specific, H-2Kk......-restricted T cell hybridomas has supported this contention. A three-dimensional model of pSAN13.4.1 has been derived by homology modeling techniques. Subsequently, the structure of the pSAN13.4.1 antibody in complex with the antigenic Ha-Kk ligand was derived after a flexible and automated docking of the MHC...

  13. A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity. (United States)

    Biamino, Elisa; Di Gregorio, Eleonora; Belligni, Elga Fabia; Keller, Roberto; Riberi, Evelise; Gandione, Marina; Calcia, Alessandro; Mancini, Cecilia; Giorgio, Elisa; Cavalieri, Simona; Pappi, Patrizia; Talarico, Flavia; Fea, Antonio M; De Rubeis, Silvia; Cirillo Silengo, Margherita; Ferrero, Giovanni Battista; Brusco, Alfredo


    Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array-CGH analysis, we identified a novel familial 3q29 deletion (1.36 Mb), centromeric to the 3q29 deletion region, which manifests with variable expressivity. The deletion was identified in a 3-year-old girl diagnosed with ID/DD and autism and segregated in six family members, all affected by severe psychiatric disorders including schizophrenia, major depression, anxiety disorder, and personality disorder. All individuals carrying the deletion were overweight or obese, and anomalies compatible with optic atrophy were observed in three out of four cases examined. Amongst the 10 genes encompassed by the deletion, the haploinsufficiency of Optic Atrophy 1 (OPA1), associated with autosomal dominant optic atrophy, is likely responsible for the ophthalmological anomalies. We hypothesize that the haploinsufficiency of ATPase type 13A4 (ATP13A4) and/or Hairy/Enhancer of Split Drosophila homolog 1 (HES1) contribute to the neuropsychiatric phenotype, while HES1 deletion might underlie the overweight/obesity. In conclusion, we propose a novel contiguous gene syndrome due to a proximal 3q29 deletion variably associated with autism, ID/DD, psychiatric traits and overweight/obesity. © 2015 Wiley Periodicals, Inc.

  14. Major depression (United States)

    Depression - major; Depression - clinical; Clinical depression; Unipolar depression; Major depressive disorder ... providers do not know the exact causes of depression. It is believed that chemical changes in the ...

  15. Seven gene deletions in seven days

    DEFF Research Database (Denmark)

    Ingemann Jensen, Sheila; Lennen, Rebecca; Herrgard, Markus


    Generation of multiple genomic alterations is currently a time consuming process. Here, a method was established that enables highly efficient and simultaneous deletion of multiple genes in Escherichia coli. A temperature sensitive plasmid containing arabinose inducible lambda Red recombineering ...

  16. CCAAT/enhancer binding protein β deletion increases mitochondrial function and protects mice from LXR-induced hepatic steatosis

    International Nuclear Information System (INIS)

    Rahman, Shaikh M.; Choudhury, Mahua; Janssen, Rachel C.; Baquero, Karalee C.; Miyazaki, Makoto; Friedman, Jacob E.


    Highlights: ► LXR agonist activation increases liver TG accumulation by increasing lipogenesis. ► C/EBPβ −/− mouse prevents LXR activation-mediated induction of hepatic lipogenesis. ► C/EBPβ deletion increases mitochondrial transport chain function. ► Beneficial effects of LXR activation on liver cholesterol metabolism did not change. ► C/EBPβ inhibition might have important therapeutic potential. -- Abstract: Drugs designed specifically to activate liver X receptors (LXRs) have beneficial effects on lowering cholesterol metabolism and inflammation but unfortunately lead to severe hepatic steatosis. The transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) is an important regulator of liver gene expression but little is known about its involvement in LXR-based steatosis and cholesterol metabolism. The present study investigated the role of C/EBPβ expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBPβ deletion in mice prevented LXR agonist-mediated induction of lipogenic gene expression in liver in conjunction with significant reduction of liver TG accumulation. Surprisingly, C/EBPβ −/− mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBPβ −/− mice increased the expression of liver ATP-binding cassette transporter ABCG1, a gene implicated in cholesterol efflux and reducing blood levels of total and LDL-cholesterol. Together, these findings establish a central role for C/EBPβ in the LXR-mediated steatosis and mitochondrial function, without impairing the influence of LXR activation on lowering LDL and increasing HDL-cholesterol. Inactivation of C/EBPβ might therefore be an important therapeutic strategy to prevent LXR activation-mediated adverse effects on liver TG metabolism without disrupting its beneficial effects on cholesterol metabolism.

  17. Conditional Deletion of Pten Causes Bronchiolar Hyperplasia


    Davé, Vrushank; Wert, Susan E.; Tanner, Tiffany; Thitoff, Angela R.; Loudy, Dave E.; Whitsett, Jeffrey A.


    Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that regulates multiple cellular processes including cell polarity, migration, proliferation, and carcinogenesis. In this work, we demonstrate that conditional deletion of Pten (PtenΔ/Δ) in the respiratory epithelial cells of the developing mouse lung caused epithelial cell proliferation and hyperplasia as early as 4 to 6 weeks of age. While bronchiolar cell differentiation was normal, as in...

  18. Thorough analysis of unorthodox ABO deletions called by the 1000 Genomes project. (United States)

    Möller, M; Hellberg, Å; Olsson, M L


    ABO remains the clinically most important blood group system, but despite earlier extensive research, significant findings are still being made. The vast majority of catalogued ABO null alleles are based on the c.261delG polymorphism. Apart from c.802G>A, other mechanisms for O alleles are rare. While analysing the data set from the 1000 Genomes (1000G) project, we encountered two previously uncharacterized deletions, which needed further exploration. The Erythrogene database, complemented with bioinformatics software, was used to analyse ABO in 2504 individuals from 1000G. DNA samples from selected 1000G donors and African blood donors were examined by allele-specific PCR and Sanger sequencing to characterize predicted deletions. A 5821-bp deletion encompassing exons 5-7 was called in twenty 1000G individuals, predominantly Africans. This allele was confirmed and its exact deletion point defined by bioinformatic analyses and in vitro experiments. A PCR assay was developed, and screening of African samples revealed three donors heterozygous for this deletion, which was thereby phenotypically established as an O allele. Analysis of upstream genetic markers indicated an ancestral origin from ABO*O.01.02. We estimate this deletion as the 3rd most common mechanism behind O alleles. A 24-bp deletion was called in nine individuals and showed greater diversity regarding ethnic distribution and allelic background. It could neither be confirmed by in silico nor in vitro experiments. A previously uncharacterized ABO deletion among Africans was comprehensively mapped and a genotyping strategy devised. The false prediction of another deletion emphasizes the need for cautious interpretation of NGS data and calls for strict validation routines. © 2017 International Society of Blood Transfusion.

  19. Betting Against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse

    We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model’s five central predictions: (1) Since constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for U...... of the BAB factor is low; (4) Increased funding liquidity risk compresses betas toward one; (5) More constrained investors hold riskier assets........S. equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures; (2) A betting-against-beta (BAB) factor, which is long leveraged low beta assets and short high-beta assets, produces significant positive risk-adjusted returns; (3) When funding constraints tighten, the return...

  20. Roughing up Beta

    DEFF Research Database (Denmark)

    Bollerslev, Tim; Li, Sophia Zhengzi; Todorov, Viktor

    -section. An investment strategy that goes long stocks with high jump betas and short stocks with low jump betas produces significant average excess returns. These higher risk premiums for the discontinuous and overnight market betas remain significant after controlling for a long list of other firm characteristics......Motivated by the implications from a stylized equilibrium pricing framework, we investigate empirically how individual equity prices respond to continuous, or \\smooth," and jumpy, or \\rough," market price moves, and how these different market price risks, or betas, are priced in the cross......-section of expected returns. Based on a novel highfrequency dataset of almost one-thousand individual stocks over two decades, we find that the two rough betas associated with intraday discontinuous and overnight returns entail significant risk premiums, while the intraday continuous beta is not priced in the cross...

  1. The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer (United States)


    Background Qualitative and quantitative changes in human mitochondrial DNA (mtDNA) have been implicated in various cancer types. A 4,977 bp deletion in the major arch of the mitochondrial genome is one of the most common mutations associated with a variety of human diseases and aging. Methods We conducted a comprehensive study on clinical features and mtDNA of 104 colorectal cancer patients in the Wenzhou area of China. In particular, using a quantitative real time PCR method, we analyzed the 4,977 bp deletion and mtDNA content in tumor tissues and paired non-tumor areas from these patients. Results We found that the 4,977 bp deletion was more likely to be present in patients of younger age (≤65 years, p = 0.027). In patients with the 4,977 bp deletion, the deletion level decreased as the cancer stage advanced (p = 0.031). Moreover, mtDNA copy number in tumor tissues of patients with this deletion increased, both compared with that in adjacent non-tumor tissues and with in tumors of patients without the deletion. Such mtDNA content increase correlated with the levels of the 4,977 bp deletion and with cancer stage (p deletion may play a role in the early stage of colorectal cancer, and it is also implicated in alteration of mtDNA content in cancer cells. PMID:21232124


    Institute of Scientific and Technical Information of China (English)


    Objective: To investigate the abnormality of p15 gene in brain glioma and the correlation of it with occurrence or malignant progression of brain glioma. Methods: Deletion and 5'CPG island methylation of p15 gene were detected by the methods of PCR and PCR-based methylation in 56 cases of brain glioma. Results: Out of 43 cases of high grade glioma, 14 cases were found to have homozygous deletion of p15E1, while none of the 13 cases of low grade glioma was found to have deletion of p15E1 (P<0.05). Methylation of 5'CPG Island of p15 gene was found only in four cases of glioma. Conclusion: Abnormality of p15 gene may involved in the occurrence and malignant progression of brain glioma. Homozygous deletion of gene is the major mechanism of inactivation for p15 gene in brain glioma.

  3. Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

    Directory of Open Access Journals (Sweden)

    Colovati Mileny ES


    Full Text Available Abstract Background The majority of Marfan syndrome (MFS cases is caused by mutations in the fibrillin-1 gene (FBN1, mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature. Results We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15. Discussion This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

  4. Deletion analysis of susy-sl promoter for the identification of optimal promoter sequence

    International Nuclear Information System (INIS)

    Bacha, S.; Khatoon, A.; Asif, M.; Bshir, A.


    The promoter region of sucrose synthase (susy-Sl) was identified and isolated from tomato. The 5? deletion analysis was carried out for the identification of minimum optimal promoter. Transgenic lines of Arabidopsis thaliana were developed by floral dip method incorporating various promoter deletion cassettes controlling GUS reporter gene. GUS assay of transgenic tissues indicated that full length susy-Sl promoter and its deletion mutants were constitutively expressed in vegetative and floral tissues of A. thaliana. The expression was observed in roots, shoots and flowers of A. thaliana. Analysis of 5? deletion series of susy-Sl promoter showed that a minimum of 679 bp fragment of the promoter was sufficient to drive expression of GUS reporter gene in the major tissues of transgenic A. thaliana. (author)

  5. Distinct phenotype of PHF6 deletions in females. (United States)

    Di Donato, N; Isidor, B; Lopez Cazaux, S; Le Caignec, C; Klink, B; Kraus, C; Schrock, E; Hackmann, K


    We report on two female patients carrying small overlapping Xq26.2 deletions of 100 kb and 270 kb involving the PHF6 gene. Mutations in PHF6 have been reported in individuals with Borjeson-Forssman-Lehmann syndrome, a condition present almost exclusively in males. Two very recent papers revealed de novo PHF6 defects in seven female patients with intellectual disability and a phenotype resembling Coffin-Siris syndrome (sparse hair, bitemporal narrowing, arched eyebrows, synophrys, high nasal root, bulbous nasal tip, marked clinodactyly with the hypoplastic terminal phalanges of the fifth fingers and cutaneous syndactyly of the toes, Blaschkoid linear skin hyperpigmentation, dental anomalies and occasional major malformations). The clinical presentation of these patients overlaps completely with our first patient, who carries a germline deletion involving PHF6. The second patient has a mosaic deletion and presented with a very mild phenotype of PHF6 loss in females. Our report confirms that PHF6 loss in females results in a recognizable phenotype overlapping with Coffin-Siris syndrome and distinct from Borjeson-Forssman-Lehmann syndrome. We expand the clinical spectrum and provide the first summary of the recommended medical evaluation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Beta limits for ETF

    International Nuclear Information System (INIS)

    Helton, F.J.; Miller, R.L.


    ETF (Engineering Test Facility) one-dimensional transport simulations indicate that a volume-average beta of 4% is required for ignition. It is therefore important that theoretical beta limits, determined by requiring equilibria to be stable to all ideal modes, exceed 4%. This paper documents an ideal MHD analysis wherein it is shown that, with appropriate plasma cross-sectional shape and current profile optimization, operation near 5% is possible. The critical beta value, however, depends on the functional form used for ff', which suggests that higher critical betas could be achieved by directly optimizing the safety factor profile. (author)

  7. Beta-energy averaging and beta spectra

    International Nuclear Information System (INIS)

    Stamatelatos, M.G.; England, T.R.


    A simple yet highly accurate method for approximately calculating spectrum-averaged beta energies and beta spectra for radioactive nuclei is presented. This method should prove useful for users who wish to obtain accurate answers without complicated calculations of Fermi functions, complex gamma functions, and time-consuming numerical integrations as required by the more exact theoretical expressions. Therefore, this method should be a good time-saving alternative for investigators who need to make calculations involving large numbers of nuclei (e.g., fission products) as well as for occasional users interested in restricted number of nuclides. The average beta-energy values calculated by this method differ from those calculated by ''exact'' methods by no more than 1 percent for nuclides with atomic numbers in the 20 to 100 range and which emit betas of energies up to approximately 8 MeV. These include all fission products and the actinides. The beta-energy spectra calculated by the present method are also of the same quality

  8. A novel large deletion of the ICR1 region including H19 and putative enhancer elements. (United States)

    Fryssira, Helen; Amenta, Stella; Kanber, Deniz; Sofocleous, Christalena; Lykopoulou, Evangelia; Kanaka-Gantenbein, Christina; Cerrato, Flavia; Lüdecke, Hermann-Josef; Bens, Susanne; Riccio, Andrea; Buiting, Karin


    Beckwith-Wiedemann syndrome (BWS) is a rare pediatric overgrowth disorder with a variable clinical phenotype caused by deregulation affecting imprinted genes in the chromosomal region 11p15. Alterations of the imprinting control region 1 (ICR1) at the IGF2/H19 locus resulting in biallelic expression of IGF2 and biallelic silencing of H19 account for approximately 10% of patients with BWS. The majority of these patients have epimutations of the ICR1 without detectable DNA sequence changes. Only a few patients were found to have deletions. Most of these deletions are small affecting different parts of the ICR1 differentially methylated region (ICR1-DMR) removing target sequences for CTCF. Only a very few deletions reported so far include the H19 gene in addition to the CTCF binding sites. None of these deletions include IGF2. A male patient was born with hypotonia, facial dysmorphisms and hypoglycemia suggestive of Beckwith-Wiedemann syndrome. Using methylation-specific (MS)-MLPA (Multiplex ligation-dependent probe amplification) we have identified a maternally inherited large deletion of the ICR1 region in a patient and his mother. The deletion results in a variable clinical expression with a classical BWS in the mother and a more severe presentation of BWS in her son. By genome-wide SNP array analysis the deletion was found to span ~100 kb genomic DNA including the ICR1DMR, H19, two adjacent non-imprinted genes and two of three predicted enhancer elements downstream to H19. Methylation analysis by deep bisulfite next generation sequencing revealed hypermethylation of the maternal allele at the IGF2 locus in both, mother and child, although IGF2 is not affected by the deletion. We here report on a novel large familial deletion of the ICR1 region in a BWS family. Due to the deletion of the ICR1-DMR CTCF binding cannot take place and the residual enhancer elements have access to the IGF2 promoters. The aberrant methylation (hypermethylation) of the maternal IGF2

  9. Fluorescence in situ hybridization evaluation of chromosome deletion patterns in prostate cancer. (United States)

    Huang, S F; Xiao, S; Renshaw, A A; Loughlin, K R; Hudson, T J; Fletcher, J A


    Various nonrandom chromosomal aberrations have been identified in prostate carcinoma. These aberrations include deletions of several chromosome regions, particularly the chromosome 8 short arm. Large-scale numerical aberrations, reflected in aberrant DNA ploidy, are also found in a minority of cases. However, it is unclear whether prostate carcinomas contain aberrations of certain chromosome regions that are deleted frequently in other common types of cancer. In this study, we performed dual-color fluorescence in situ hybridization on intact nuclei from touch preparations of 16 prostate cancers. Chromosome copy number was determined using pericentromeric probes, whereas potential chromosome arm deletions were evaluated using yeast artificial chromosome (YAC) and P1 probes. Two YAC probes targeted chromosome 8 short arm regions known to be deleted frequently in prostate cancer. Other YACs and P1s were for chromosome regions, including 1p22, 3p14, 6q21, 9p21, and 22q12, that are deletion targets in a variety of cancers although not extensively studied in prostate cancer. Hybridization efficiencies and signal intensities were excellent for both repeat sequence (alpha-satellite) and single, copy (YAC and P1) fluorescence in situ hybridization probes. Of 16 prostate cancers, 11 had clonal aberrations of 1 or more of the 13 chromosome regions evaluated, and 10 cases (62.5%) had 8p deletions, including 4 cases with 8p deletion in virtually all cells and aneuploidy in only a subset of those deleted cells. Deletions at 3p14, 6q21, and 22q12 were identified in 2, 1, and 1 case, respectively, and each of those cases had a similarly sized cell population with 8p deletion. These studies confirm 8p deletion in the majority of prostate carcinomas. 8p deletions appear to be early events in prostate tumorigenesis, often antedating aneuploidy. Fluorescence in situ hybridization strategies incorporating pericentromeric and single-copy regional chromosome probes offer a powerful and

  10. 17q12 Deletion in a patient with Williams syndrome: Case report and review of the literature. (United States)

    Cohen, Lilian; Samanich, Joy; Pan, Quilu; Mehta, Lakshmi; Marion, Robert


    Williams syndrome (WS) is a complex genomic disorder entailing distinctive facial dysmorphism, cardiovascular abnormalities, intellectual disabilities, unusual behavioral features, and a specific cognitive profile with considerable variability. Additional symptoms include endocrine abnormalities, renal anomalies and connective tissue disorders. We report a monozygotic twin patient with WS who presented with multicystic kidneys in the newborn period, and, in addition to the typical WS deletion at 7q11.23, was found to have a de novo 1.7 Mb deletion in the 17q12 region on microarray comparative genomic hybridization. The co-twin was selectively terminated at 23 wk of gestation after being diagnosed with bilateral multicystic dysplastic kidneys and anhydramnios. Review of the literature shows that deletion of chromosome 17q12, encompassing hepatocyte nuclear factor 1beta gene, is associated with cystic renal disease and is the first recurrent genomic deletion associated with maturity onset diabetes of the young. In addition, reports of female reproductive tract malformations and patients with neurocognitive or psychiatric phenotypes have recently been described. This review of the literature summarizes 47 other cases involving 17q12 deletions with wide variability in phenotype, possibly suggesting a contiguous gene syndrome. It is likely that the additional 17q12 deletion has played a role in modifying the phenotype in our patient. This case highlights the importance of using array comparative genomic hybridization in the clinical setting to uncover the etiology of atypical findings in individuals with known microdeletion syndromes.

  11. 46 CFR 67.171 - Deletion; requirement and procedure. (United States)


    ... 46 Shipping 2 2010-10-01 2010-10-01 false Deletion; requirement and procedure. 67.171 Section 67...; Requirement for Exchange, Replacement, Deletion, Cancellation § 67.171 Deletion; requirement and procedure. (a... provided in § 67.161, and the vessel is subject to deletion from the roll of actively documented vessels...

  12. 19 CFR 142.49 - Deletion of C-4 Code. (United States)


    .... Entry filers may delete C-4 Codes from Line Release by notifying the port director in writing on a Deletion Data Loading Sheet. Such notification shall state the C-4 Code which is to be deleted, the port... TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.49 Deletion of C-4 Code. (a) By Customs. A port...

  13. High beta tokamaks

    International Nuclear Information System (INIS)

    Dory, R.A.; Berger, D.P.; Charlton, L.A.; Hogan, J.T.; Munro, J.K.; Nelson, D.B.; Peng, Y.K.M.; Sigmar, D.J.; Strickler, D.J.


    MHD equilibrium, stability, and transport calculations are made to study the accessibility and behavior of ''high beta'' tokamak plasmas in the range β approximately 5 to 15 percent. For next generation devices, beta values of at least 8 percent appear to be accessible and stable if there is a conducting surface nearby

  14. Sorting out Downside Beta

    NARCIS (Netherlands)

    G.T. Post (Thierry); P. van Vliet (Pim); S.D. Lansdorp (Simon)


    textabstractDownside risk, when properly defined and estimated, helps to explain the cross-section of US stock returns. Sorting stocks by a proper estimate of downside market beta leads to a substantially larger cross-sectional spread in average returns than sorting on regular market beta. This

  15. Betting against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse


    We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model's five central predictions: (1) Because constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically...

  16. Oncogenic activation of v-kit involves deletion of a putative tyrosine-substrate interaction site. (United States)

    Herbst, R; Munemitsu, S; Ullrich, A


    The transforming gene of the Hardy-Zuckerman-4 strain of feline sarcoma virus, v-kit, arose by transduction of the cellular c-kit gene, which encodes the receptor tyrosine kinase (RTK) p145c-kit. To gain insight into the molecular basis of the v-kit transforming potential, we characterized the feline c-kit by cDNA cloning. Comparison of the feline v-kit and c-kit sequences revealed, in addition to deletions of the extracellular and transmembrane domains, three additional mutations in the v-kit oncogene product: deletion of tyrosine-569 and valine-570, the exchange of aspartate at position 761 to glycine, and replacement of the C-terminal 50 amino acids by five unrelated residues. Examinations of individual v-kit mutations in the context of chimeric receptors yielded inhibitory effects for some mutants on both autophosphorylation and substrate phosphorylation functions. In contrast, deletion of tyrosine-569 and valine-570 significantly enhanced transforming and mitogenic activities of p145c-kit, while the other mutations had no significant effects. Conservation in subclass III RTKs and the identification of the corresponding residue in beta PDGF-R, Y579, as a binding site for src family tyrosine kinases suggests an important role for Y568 in kit signal regulation and the definition of its oncogenic potential. Repositioning of Y571 by an inframe two codon deletion may be the crucial alteration resulting in enhancement of v-kit oncogenic activity.

  17. Rapid deletion production in fungi via Agrobacterium mediated transformation of OSCAR deletion contructs. (United States)

    Precise deletion of gene(s) of interest, while leaving the rest of the genome unchanged, provides the ideal product to determine that particular gene’s function in the living organism. In this protocol we describe the OSCAR method of precise and rapid deletion plasmid construction. OSCAR relies on t...

  18. The fate of deleted DNA produced during programmed genomic deletion events in Tetrahymena thermophila. (United States)

    Saveliev, S V; Cox, M M


    Thousands of DNA deletion events occur during macronuclear development in the ciliate Tetrahymena thermophila. In two deleted genomic regions, designated M and R, the eliminated sequences form circles that can be detected by PCR. However, the circles are not normal products of the reaction pathway. The circular forms occur at very low levels in conjugating cells, but are stable. Sequencing analysis showed that many of the circles (as many as 50% of those examined) reflected a precise deletion in the M and R regions. The remaining circles were either smaller or larger and contained varying lengths of sequences derived from the chromosomal DNA surrounding the eliminated region. The chromosomal junctions left behind after deletion were more precise, although deletions in either the M or R regions can generate any of several alternative junctions (1). Some new chromosomal junctions were detected in the present study. The results suggest that the deleted segment is released as a linear DNA species that is degraded rapidly. The species is only rarely converted to the stable circles we detect. The deletion mechanism is different from those proposed for deletion events in hypotrichous ciliates (2-4), and does not reflect a conservative site-specific recombination process such as that promoted by the bacteriophage lambda integrase (5). Images PMID:7838724

  19. Genetics Home Reference: beta thalassemia (United States)

    ... Facebook Twitter Home Health Conditions Beta thalassemia Beta thalassemia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Beta thalassemia is a blood disorder that reduces the production ...

  20. The effects of beta-carotene and vitamin E on erythrocytes lipid peroxidation in beta-thalassemia patients

    Directory of Open Access Journals (Sweden)

    Soleiman Mahjoub


    Full Text Available BACKGROUND: Thalassemia is the most common hereditary disease in the world. Thalassemic erythrocytes are exposed to higher oxidative stress and lipid peroxidation. The aim of this study was to investigate the effects of beta-carotene and vitamin E on erythrocytes lipid peroxidation in beta-thalassemia patients.
    METHODS: A prospective double-blind, placebo-controlled study of the effect of beta-carotene and vitamin E on lipid peroxidation in erythrocytes membranes was performed on 120 beta-thalassemia major patients in four groups. The patients were supplemented for 4 weeks as follows: group 1 with beta-carotene (13 mg/day, group 2 with vitamin E (550 mg/day, group 3 with beta-carotene plus vitamin E and group 4 with placebo. We prepared all capsules for 4 roups in the same shape and color. Measurements of serum beta-carotene and vitamin E were performed by high performance
    liquid chromatography. After preparation of ghost cells from blood specimens, malondialdehyde (MDA was determined as index of lipid peroxidation in erythrocytes membranes before and after treatment. RESULTS: The levels of serum beta-carotene and vitamin E were significantly lower and MDA concentrations in erythrocytes membranes were significantly higher in beta-thalassemia patients compared to controls (P<0.001. In groups that treated with vitamin supplements for 4-weeks, lipid peroxidation rates were significantly reduced after treatment (P<0.001, but in placebo group there was not significant difference (P>0.05.
    CONCLUSIONS: Our findings provide evidence that an oral treatment with beta-carotene and vitamin E can significantly reduce lipid peroxidation of erythrocytes membranes and could be useful in management of beta-thalassemia major patients. KEYWORDS: Beta-thalassemia major, beta-carotene, vitamin E, malondialdehyde, lipid peroxidation.

  1. Identification of differentially expressed proteins in spontaneous thymic lymphomas from knockout mice with deletion of p53

    DEFF Research Database (Denmark)

    Honoré, Bent; Buus, Søren; Claësson, Mogens H


    ABSTRACT: BACKGROUND: Knockout mice with a deletion of p53 spontaneously develop thymic lymphomas. Two cell lines (SM5 and SM7), established from two independent tumours, exhibited about fifty to seventy two-fold differentially expressed proteins compared to wild type thymocytes by two-dimensiona......ABSTRACT: BACKGROUND: Knockout mice with a deletion of p53 spontaneously develop thymic lymphomas. Two cell lines (SM5 and SM7), established from two independent tumours, exhibited about fifty to seventy two-fold differentially expressed proteins compared to wild type thymocytes by two...... alpha type 3, transforming acidic coiled-coil containing protein 3, mitochondrial ornithine aminotransferase and epidermal fatty acid binding protein and down-regulation of adenylosuccinate synthetase, tubulin beta-3 chain, a 25 kDa actin fragment, proteasome subunit beta type 9, cofilin-1 and glia...

  2. Rapid synthesis of beta zeolites (United States)

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng


    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  3. Mitochondrial common deletion is elevated in blood of breast cancer patients mediated by oxidative stress. (United States)

    Nie, Hezhongrong; Chen, Guorong; He, Jing; Zhang, Fengjiao; Li, Ming; Wang, Qiufeng; Zhou, Huaibin; Lyu, Jianxin; Bai, Yidong


    The 4977 bp common deletion is one of the most frequently observed mitochondrial DNA (mtDNA) mutations in human tissues and has been implicated in various human cancer types. It is generally believed that continuous generation of intracellular reactive oxygen species (ROS) during oxidative phosphorylation (OXPHOS) is a major underlying mechanism for generation of such mtDNA deletions while antioxidant systems, including Manganese superoxide dismutase (MnSOD), mitigating the deleterious effects of ROS. However, the clinical significance of this common deletion remains to be explored. A comprehensive investigation on occurrence and accumulation of the common deletion and mtDNA copy number was carried out in breast carcinoma (BC) patients, benign breast disease (BBD) patients and age-matched healthy donors in our study. Meanwhile, the representative oxidative (ROS production, mtDNA and lipid oxidative damage) and anti-oxidative features (MnSOD expression level and variation) in blood samples from these groups were also analyzed. We found that the mtDNA common deletion is much more likely to be detected in BC patients at relatively high levels while the mtDNA content is lower. This alteration has been associated with a higher MnSOD level and higher oxidative damages in both BC and BBD patients. Our results indicate that the mtDNA common deletion in blood may serve a biomarker for the breast cancer. Copyright © 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  4. Deletion analysis of SMN1 and NAIP genes in southern Chinese children with spinal muscular atrophy

    Institute of Scientific and Technical Information of China (English)

    Yu-hua LIANG; Xiao-ling CHEN; Zhong-sheng YU; Chun-yue CHEN; Sheng BI; Lian-gen MAO; Bo-lin ZHOU; Xian-ning ZHANG


    Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis as well as muscular atrophy. Three types of SMA are rec-ognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: SMA1, SMA2, and SMA3. The survival of motor neuron (SMN) gene has been identified as an SMA determining gene, whereas the neuronal apoptosis inhibitory protein (NAIP) gene is considered to be a modifying factor of the severity of SMA. The main objective of this study was to analyze the deletion of SMN1 and NAIP genes in southern Chinese children with SMA. Here, polymerase chain reaction (PCR) combined with restriction fragment length polymorphism (RFLP) was performed to detect the deletion of both exon 7 and exon 8 of SMNI and exon 5 of NAIP in 62 southern Chinese children with strongly suspected clinical symptoms of SMA. All the 32 SMAI patients and 76% (13/17) of SMA2 patients showed homozygous deletions for exon 7 and exon 8, and all the 13 SMA3 patients showed single deletion of SMN1 exon 7 along with 24% (4/17) of SMA2 patients. Eleven out of 32 (34%) SMA1 patients showed NAIP deletion, and none of SMA2 and SMA3 patients was found to have NAIP deletion. The findings of homozygous deletions of exon 7 and/or exon 8 of SMN1 gene confirmed the diagnosis of SMA, and suggested that the deletion of SMN1 exon 7 is a major cause of SMA in southern Chinese children, and that the NA1P gene may be a modifying factor for disease severity of SMA 1. The molecular diagnosis system based on PCR-RFLP analysis can conveniently be applied in the clinical testing, genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis of SMA.

  5. 9q22 Deletion - First Familial Case

    Directory of Open Access Journals (Sweden)

    Yamamoto Toshiyuki


    Full Text Available Abstract Background Only 29 cases of constitutional 9q22 deletions have been published and all have been sporadic. Most associate with Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS, MIM #109400 due to haploinsufficiency of the PTCH1 gene (MIM *601309. Methods and Results We report two mentally retarded female siblings and their cognitively normal father, all carrying a similar 5.3 Mb microdeletion at 9q22.2q22.32, detected by array CGH (244 K. The deletion does not involve the PTCH1 gene, but instead 30 other gene,s including the ROR2 gene (MIM *602337 which causing both brachydactyly type 1 (MIM #113000 and Robinow syndrome (MIM #268310, and the immunologically active SYK gene (MIM *600085. The deletion in the father was de novo and FISH analysis of blood lymphocytes did not suggest mosaicism. All three patients share similar mild dysmorphic features with downslanting palpebral fissures, narrow, high bridged nose with small nares, long, deeply grooved philtrum, ears with broad helix and uplifted lobuli, and small toenails. All have significant dysarthria and suffer from continuous middle ear and upper respiratory infections. The father also has a funnel chest and unilateral hypoplastic kidney but the daughters have no malformations. Conclusions This is the first report of a familial constitutional 9q22 deletion and the first deletion studied by array-CGH which does not involve the PTCH1 gene. The phenotype and penetrance are variable and the deletion found in the cognitively normal normal father poses a challenge in genetic counseling.

  6. Deletion 22q13.3 syndrome

    Directory of Open Access Journals (Sweden)

    Phelan Mary C


    Full Text Available Abstract The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndrome is under-diagnosed and its true incidence remains unknown. Common physical traits include long eye lashes, large or unusual ears, relatively large hands, dysplastic toenails, full brow, dolicocephaly, full cheeks, bulbous nose, and pointed chin. Behavior is autistic-like with decreased perception of pain and habitual chewing or mouthing. The loss of 22q13.3 can result from simple deletion, translocation, ring chromosome formation and less common structural changes affecting the long arm of chromosome 22, specifically the region containing the SHANK3 gene. The diagnosis of deletion 22q13 syndrome should be considered in all cases of hypotonia of unknown etiology and in individuals with absent speech. Although the deletion can sometimes be detected by high resolution chromosome analysis, fluorescence in situ hybridization (FISH or array comparative genomic hybridization (CGH is recommended for confirmation. Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like affect (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders, cerebral palsy. Genetic counseling is recommended and parental laboratory studies should be considered to identify cryptic rearrangements and detect parental mosaicism. Prenatal diagnosis should be offered for future pregnancies in those families with inherited rearrangements


    Directory of Open Access Journals (Sweden)

    Seham Ragab


    Full Text Available Background: Cardiac iron toxicity is the leading cause of death among  β-halassaemia major (TM  patients.  Once  heart failure becomes overt , it will be  difficult to reverse . Objectives: To investigate non overt cardiac dysfunctions  in TM patients using  pulsed wave Tissue Doppler  Imaging (TD I and its relation to the iron overload and brain natruritic peptide (BNP. Methods: Thorough  clinical , conventional echo and  pulsed  wave TDI  parameters were compared between  asymtomatic 25 β-TM  patients  and 20 age and gender matched individuals. Serum ferritin and plasma BNP  levels were assayed by  ELISA .  Results: TM patients had significant higher mitral inflow early diastolic (E wave and  non significant other conventional echo  parameters. Pulsed wave TDI revealed systolic and diastolic dysfunctions in the form of significant higher  isovolumetric contraction time (ICT , ejection time ( E T and  isovolumetric relaxation time (IRT with significantly lower  mitral annulus  early diastolic velocity E` (12.07 ±2.06 vs 15.04±2.65 ,P= 0.003  in patients compared to  controls. Plasma BNP was higher in patients compared to the controls.  Plasma BNP and serum ferritin had significant correlation with each other and with pulsed wave conventional and TDI indices of systolic and diastolic functions.  Patients with E/E` ≥ 8 had  significant higher  serum ferritin  and plasma BNP levels compared to those with E/E` ratio < 8 without difference in Hb levels .Conclusion:  Pulsed wave TDI  is an  important diagnostic tool for latent cardiac dysfunction in iron loaded TM patients and is related to iron overload and BNP .

  8. The Diagnostic Value of Pulsed Wave Tissue Doppler Imaging in Asymptomatic Beta- Thalassemia Major Children and Young Adults; Relation to Chemical Biomarkers of Left Ventricular Function and Iron Overload. (United States)

    Ragab, Seham M; Fathy, Waleed M; El-Aziz, Walaa FAbd; Helal, Rasha T


    Cardiac iron toxicity is the leading cause of death among β-halassaemia major (TM) patients. Once heart failure becomes overt, it is difficult to reverse. To investigate non-overt cardiac dysfunctions in TM patients using pulsed wave Tissue Doppler Imaging (TD I) and its relation to iron overload and brain natriuretic peptide (BNP). Thorough clinical, conventional echo and pulsed wave TDI parameters were compared between asymptomatic 25 β-TM patients and 20 age and gender matched individuals. Serum ferritin and plasma BNP levels were assayed by ELISA. TM patients had significant higher mitral inflow early diastolic (E) wave and non significant other conventional echo parameters. In the patient group, pulsed wave TDI revealed systolic dysfunctions, in the form of significant higher isovolumetric contraction time (ICT), and lower ejection time (E T), with diastolic dysfunction in the form of higher isovolumetric relaxation time (IRT), and lower mitral annulus early diastolic velocity E' (12.07 ±2.06 vs 15.04±2.65, P= 0.003) compared to the controls. Plasma BNP was higher in patients compared to the controls. Plasma BNP and serum ferritin had a significant correlation with each other and with pulsed wave conventional and TDI indices of systolic and diastolic functions. Patients with E/E' ≥ 8 had significant higher serum ferritin and plasma BNP levels compared to those with ratio wave TDI is an important diagnostic tool for latent cardiac dysfunction in iron-loaded TM patients and is related to iron overload and BNP.

  9. Beta particle measurement fundamentals

    International Nuclear Information System (INIS)

    Alvarez, J.L.


    The necessary concepts for understanding beta particle behavior are stopping power, range, and scattering. Dose as a consequence of beta particle interaction with tissue can be derived and explained by these concepts. Any calculations of dose, however, assume or require detailed knowledge of the beta spectrum at the tissue depth of calculation. A rudimentary knowledge of the incident spectrum can be of use in estimating dose, interpretating dose measuring devices and designing protection. The stopping power and range based on the csda will give a conservative estimate in cases of protection design, as scattering will reduce the range. Estimates of dose may be low because scattering effects were neglected

  10. DELISHUS: an efficient and exact algorithm for genome-wide detection of deletion polymorphism in autism (United States)

    Aguiar, Derek; Halldórsson, Bjarni V.; Morrow, Eric M.; Istrail, Sorin


    Motivation: The understanding of the genetic determinants of complex disease is undergoing a paradigm shift. Genetic heterogeneity of rare mutations with deleterious effects is more commonly being viewed as a major component of disease. Autism is an excellent example where research is active in identifying matches between the phenotypic and genomic heterogeneities. A considerable portion of autism appears to be correlated with copy number variation, which is not directly probed by single nucleotide polymorphism (SNP) array or sequencing technologies. Identifying the genetic heterogeneity of small deletions remains a major unresolved computational problem partly due to the inability of algorithms to detect them. Results: In this article, we present an algorithmic framework, which we term DELISHUS, that implements three exact algorithms for inferring regions of hemizygosity containing genomic deletions of all sizes and frequencies in SNP genotype data. We implement an efficient backtracking algorithm—that processes a 1 billion entry genome-wide association study SNP matrix in a few minutes—to compute all inherited deletions in a dataset. We further extend our model to give an efficient algorithm for detecting de novo deletions. Finally, given a set of called deletions, we also give a polynomial time algorithm for computing the critical regions of recurrent deletions. DELISHUS achieves significantly lower false-positive rates and higher power than previously published algorithms partly because it considers all individuals in the sample simultaneously. DELISHUS may be applied to SNP array or sequencing data to identify the deletion spectrum for family-based association studies. Availability: DELISHUS is available at Contact: and Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22689755

  11. The first Dutch SDHB founder deletion in paraganglioma – pheochromocytoma patients

    Directory of Open Access Journals (Sweden)

    Devilee Peter


    Full Text Available Abstract Background Germline mutations of the tumor suppressor genes SDHB, SDHC and SDHD play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH, the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described. Methods We carried out gene deletion scanning using MLPA in 126 patients negative for point mutations in the SDH genes. We then proceeded to the molecular characterization of deletions, mapping breakpoints in each patient and used haplotype analysis to determine whether the deletions are due to a mutation hotspot or if a common haplotype indicated a single founder mutation. Results A novel deletion of exon 3 of the SDHB gene was identified in nine apparently unrelated Dutch patients. An identical 7905 bp deletion, c.201-4429_287-933del, was found in all patients, resulting in a frameshift and a predicted truncated protein, p.Cys68HisfsX21. Haplotype analysis demonstrated a common haplotype at the SDHB locus. Index patients presented with pheochromocytoma, extra-adrenal PGL and HN-PGL. A lack of family history was seen in seven of the nine cases. Conclusion The identical exon 3 deletions and common haplotype in nine patients indicates that this mutation is the first Dutch SDHB founder mutation. The predominantly non-familial presentation of these patients strongly suggests reduced penetrance. In this small series HN-PGL occurs as frequently as pheochromocytoma and extra-adrenal PGL.

  12. Some analogies between quantum cloning and quantum deleting

    International Nuclear Information System (INIS)

    Qiu Daowen


    We further verify the impossibility of deleting an arbitrary unknown quantum state, and also show it is impossible to delete two nonorthogonal quantum states as a consequence of unitarity of quantum mechanics. A quantum approximate (deterministic) deleting machine and a probabilistic (exact) deleting machine are constructed. The estimation for the global fidelity characterizing the efficiency of the quantum approximate deleting is given. We then demonstrate that unknown nonorthogonal states chosen from a set with their multiple copies can evolve into a linear superposition of multiple deletions and failure branches by a unitary process if and only if the states are linearly independent. It is notable that the proof for necessity is somewhat different from Pati's [Phys. Rev. Lett. 83, 2849 (1999)]. Another deleting machine for the input states that are unnecessarily linearly independent is also presented. The bounds on the success probabilities of these deleting machines are derived. So we expound some preliminary analogies between quantum cloning and deleting

  13. Detection of glycemic abnormalities in adolescents with beta thalassemia using continuous glucose monitoring and oral glucose tolerance in adolescents and young adults with β-thalassemia major: Pilot study

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman


    Full Text Available Background: Both insulin deficiency and resistance are reported in patients with β-thalassemia major (BTM. The use of continuous blood glucose monitoring (CGM, among the different methods for early detection of glycemic abnormalities, has not been studied thoroughly in these adolescents. Materials and Methods: To assess the oralglucose tolerance (OGT and 72-h continuous glucose concentration by the continuous glucose monitoring system (CGMS and calculate homeostatic model assessment (HOMA, and the quantitative insulin sensitivity check index (QUICKI was conducted in 16 adolescents with BTM who were receiving regular blood transfusions every 2-4 weeks and iron-chelation therapy since early childhood. Results: Sixteen adolescents with BTM (age: 19.75 ± 3 years were investigated. Using OGTT, (25% had impaired fasting blood (plasma glucose concentration (BG (>5.6 mmol/L. 2-h after the glucose load, one of them had BG = 16.2 mmol/L (diabetic and two had impaired glucose tolerance (IGT (BG > 7.8 and 11.1 mmol/L and 9 with IGT (56%. HOMA and QUICKI revealed levels 0.33 (0.36 ± 0.03, respectively, ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B% on one hand and the fasting and the 2-h BG (r=−0.6, and − 0.48, P < 0.01, respectively on the other hand. Neither fasting serum insulin nor c-peptide concentrations were correlated with fasting BG or ferritin levels. The average and maximum blood glucose levels during CGM were significantly correlated with the fasting BG (r = 0.68 and 0.39, respectively, with P < 0.01 and with the BG at 2-hour after oral glucose intake (r = 0.87 and 0.86 respectively, with P < 0.001. Ferritin concentrations were correlated with the fasting BG and the 2-h blood glucose levels in the OGTT (r = 0.52, and r = 0.43, respectively, P < 0.01 as well as with the average BG recorded by CGM (r = 0.75, P < 0.01. Conclusion: CGM has proven to

  14. Mitochondrial DNA deletion and impairment of mitochondrial biogenesis are mediated by reactive oxygen species in ionizing radiation-induced premature senescence

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hyeon Soo; Jung, U Hee; Jo, Sung Kee [Radiation Biotechnology Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Young Sang [College of Natural Sciences, Chungnam National University, Daejeon (Korea, Republic of)


    Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging, and contributes to harmful effects in cultured cells and animal tissues. mtDNA biogenesis genes (NRF-1, TFAM) are essential for the maintenance of mtDNA, as well as the transcription and replication of mitochondrial genomes. Considering that oxidative stress is known to affect mitochondrial biogenesis, we hypothesized that ionizing radiation (IR)-induced reactive oxygen species (ROS) causes mtDNA deletion by modulating the mitochondrial biogenesis, thereby leading to cellular senescence. Therefore, we examined the effects of IR on ROS levels, cellular senescence, mitochondrial biogenesis, and mtDNA deletion in IMR-90 human lung fibroblast cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated at 4 or 8 Gy. Old cells at PD55, and H2O2-treated young cells at PD 39, were compared as a positive control. The IR increased the intracellular ROS level, senescence-associated {beta}-galactosidase (SA-{beta}-gal) activity, and mtDNA common deletion (4977 bp), and it decreased the mRNA expression of NRF-1 and TFAM in IMR-90 cells. Similar results were also observed in old cells (PD 55) and H{sub 2}O{sub 2}-treated young cells. To confirm that a increase in ROS level is essential for mtDNA deletion and changes of mitochondrial biogenesis in irradiated cells, the effects of N-acetylcysteine (NAC) were examined. In irradiated and H{sub 2}O{sub 2}-treated cells, 5 mM NAC significantly attenuated the increases of ROS, mtDNA deletion, and SA-{beta}-gal activity, and recovered from decreased expressions of NRF-1 and TFAM mRNA. These results suggest that ROS is a key cause of IR-induced mtDNA deletion, and the suppression of the mitochondrial biogenesis gene may mediate this process.

  15. beta-Carotene in breast milk and serum is increased after a single beta-carotene dose. (United States)

    Canfield, L M; Giuliano, A R; Neilson, E M; Yap, H H; Graver, E J; Cui, H A; Blashill, B M


    Normal lactating mothers were administered a single dose of 60 or 210 mg beta-carotene and changes in serum and milk retinol, alpha-tocopherol, and carotenoids were monitored for 8 d. Average serum beta-carotene concentrations increased 4.1- and 4.0-fold after the 60- and 210-mg doses, respectively. Milk beta-carotene concentrations increased 4.1- and 3.0-fold after the 60- and 210-mg doses, respectively. Maximum serum concentrations were reached 24 h after both supplements, although concentrations of milk beta-carotene continued to rise for 2-3 d. After 8 d, both serum and milk beta-carotene continued to rise for 2-3 d. After 8 d, both serum and milk beta-carotene concentrations remained about twofold higher than baseline concentrations. Increases in serum or milk beta-carotene concentrations were not dose-dependent. Initial serum and milk concentrations of beta-carotene predicted increases after supplementation, and increases in serum beta-carotene concentrations predicted those in milk. Concentrations of milk carotenoids were less than one-tenth their respective concentrations in serum. Lutein, beta-cryptoxanthin, lycopene, alpha-carotene, retinol, and alpha-tocopherol concentrations in serum or milk did not change significantly after beta-carotene supplementation. Retinol esters account for most of the retinol equivalents in the milk of well-nourished mothers. Initial and maximum concentrations of beta-carotene in serum and milk were strongly correlated for individual mothers. Collectively, the data showed that a single 60-mg supplement of beta-carotene sustained elevated beta-carotene concentrations in serum and milk for > 1 wk in normal mothers but did not affect concentrations of other major carotenoids, retinol, or alpha-tocopherol.

  16. Neutrinoless double beta decay

    Indian Academy of Sciences (India)


    Oct 6, 2012 ... Anyhow, the 'multi-isotope' ansatz is needed to compensate for matrix element ... The neccessary half-life requirement to touch this ... site energy depositions (like double beta decay) and multiple site interactions (most of.

  17. Beta-Carotene (United States)

    ... disease (COPD). It is also used to improve memory and muscle strength. Some people use beta-carotene ... to reduce the chance of death and night blindness during pregnancy, as well as diarrhea and fever ...

  18. Double beta decay: experiments

    International Nuclear Information System (INIS)

    Fiorini, Ettore


    The results obtained so far and those of the running experiments on neutrinoless double beta decay are reviewed. The plans for second generation experiments, the techniques to be adopted and the expected sensitivities are compared and discussed

  19. Phenotypic variability of Filipino beta(o)-thalassemia/HbE patients in Indonesia. (United States)

    Setianingsih, I; Williamson, R; Daud, D; Harahap, A; Marzuki, S; Forrest, S


    Three Indonesian patients with identical genotypes, each compound heterozygotes for Filipino beta(o)-thalassemia/HbE, expressed different clinical severities. One patient has mild disease and is transfusion independent, while the other two are severely affected and transfusion dependent. The size of the Filipino beta(o)-globin gene deletion was confirmed to be 45 kb, resolving conflicting values given in the literature. Neither ameliorating genetic factors such as alpha-globin gene deletions or the XmnI restriction site polymorphism at position -158 upstream of the (G)gamma-globin gene, nor differences in beta-globin gene haplotype, explain the phenotypic variation. These observations have implications for the development of antenatal diagnosis in Indonesia, as at present it is not possible to give an accurate prediction of severity of phenotype for this common genotype. Copyright 1999 Wiley-Liss, Inc.

  20. Familial deletion 18p syndrome: case report

    Directory of Open Access Journals (Sweden)

    Lemyre Emmanuelle


    Full Text Available Abstract Background Deletion 18p is a frequent deletion syndrome characterized by dysmorphic features, growth deficiencies, and mental retardation with a poorer verbal performance. Until now, five families have been described with limited clinical description. We report transmission of deletion 18p from a mother to her two daughters and review the previous cases. Case presentation The proband is 12 years old and has short stature, dysmorphic features and moderate mental retardation. Her sister is 9 years old and also has short stature and similar dysmorphic features. Her cognitive performance is within the borderline to mild mental retardation range. The mother also presents short stature. Psychological evaluation showed moderate mental retardation. Chromosome analysis from the sisters and their mother revealed the same chromosomal deletion: 46, XX, del(18(p11.2. Previous familial cases were consistent regarding the transmission of mental retardation. Our family differs in this regard with variable cognitive impairment and does not display poorer verbal than non-verbal abilities. An exclusive maternal transmission is observed throughout those families. Women with del(18p are fertile and seem to have a normal miscarriage rate. Conclusion Genetic counseling for these patients should take into account a greater range of cognitive outcome than previously reported.

  1. 78 FR 37525 - Procurement List; Deletions (United States)


    .... Contracting Activity: Dept of the Air Force, FA7014 AFDW A7KI, Andrews AFB, MD. Service Type/Location: Laundry... Procurement List. SUMMARY: This action deletes products and services from the Procurement List that were... products and services listed below are no longer suitable for procurement by the Federal Government under...

  2. Sequence analysis of 17 NRXN1 deletions

    DEFF Research Database (Denmark)

    Hoeffding, Louise Kristine Enggaard; Hansen, Thomas; Ingason, Andrés


    into the molecular mechanisms governing such genomic rearrangements may increase our understanding of disease pathology and evolutionary processes. Here we analyse 17 carriers of non-recurrent deletions in the NRXN1 gene, which have been associated with neurodevelopmental disorders, e.g. schizophrenia, autism...

  3. Angiotensin Converting Enzyme Insertion/Deletion Gene ...

    African Journals Online (AJOL)

    Angiotensin Converting Enzyme Insertion/Deletion Gene Polymorphism: An Observational Study among Diabetic Hypertensive Subjects in Malaysia. ... Methods: The pharmacological effect of ACE inhibition on mean arterial pressure (MAP) and glomerular filtration rate (GFR) were observed among a total of 62 subjects for ...

  4. Obtaining a Proportional Allocation by Deleting Items

    NARCIS (Netherlands)

    Dorn, B.; de Haan, R.; Schlotter, I.; Röthe, J.


    We consider the following control problem on fair allocation of indivisible goods. Given a set I of items and a set of agents, each having strict linear preference over the items, we ask for a minimum subset of the items whose deletion guarantees the existence of a proportional allocation in the

  5. Union-Find with Constant Time Deletions

    DEFF Research Database (Denmark)

    Alstrup, Stephen; Thorup, Mikkel; Gørtz, Inge Li


    operations performed, and α_M/N_(n) is a functional inverse of Ackermann’s function. They left open the question whether delete operations can be implemented more efficiently than find operations, for example, in o(log n) worst-case time. We resolve this open problem by presenting a relatively simple...

  6. Mapping genomic deletions down to the base

    DEFF Research Database (Denmark)

    Dunø, Morten; Hove, Hanne; Kirchhoff, Maria


    the breakpoint of the third patient was mapped to a region previously predicted to be prone for rearrangements. One patient also harboured an inversion in connection with the deletion that disrupted the HDAC9 gene. All three patients showed clinical characteristics reminiscent of the hand-foot-genital syndrome...

  7. {beta} - amyloid imaging probes

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    Imaging distribution of {beta} - amyloid plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the {beta} -amyloid plaques includes using radiolabeled peptides which can be only applied for peripheral {beta} - amyloid plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging {beta} - amyloid plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for {beta} - amyloid imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for {beta} - amyloid imaging agent.

  8. Delayed chromosomal instability caused by large deletion

    International Nuclear Information System (INIS)

    Ojima, M.; Suzuki, K.; Kodama, S.; Watanabe, M.


    Full text: There is accumulating evidence that genomic instability, manifested by the expression of delayed phenotypes, is induced by X-irradiation but not by ultraviolet (UV) light. It is well known that ionizing radiation, such as X-rays, induces DNA double strand breaks, but UV-light mainly causes base damage like pyrimidine dimers and (6-4) photoproducts. Although the mechanism of radiation-induced genomic instability has not been thoroughly explained, it is suggested that DNA double strand breaks contribute the induction of genomic instability. We examined here whether X-ray induced gene deletion at the hprt locus induces delayed instability in chromosome X. SV40-immortalized normal human fibroblasts, GM638, were irradiated with X-rays (3, 6 Gy), and the hprt mutants were isolated in the presence of 6-thioguanine (6-TG). A 2-fold and a 60-fold increase in mutation frequency were found by 3 Gy and 6 Gy irradiation, respectively. The molecular structure of the hprt mutations was determined by multiplex polymerase chain reaction of nine exons. Approximately 60% of 3 Gy mutants lost a part or the entire hprt gene, and the other mutants showed point mutations like spontaneous mutants. All 6 Gy mutants show total gene deletion. The chromosomes of the hprt mutants were analyzed by Whole Human Chromosome X Paint FISH or Xq telomere FISH. None of the point or partial gene deletion mutants showed aberrations of X-chromosome, however total gene deletion mutants induced translocations and dicentrics involving chromosome X. These results suggest that large deletion caused by DNA double strand breaks destabilizes chromosome structure, which may be involved in an induction of radiation-induced genomic instability

  9. Association of the UCP2 45-bp insertion/deletion polymorphism with ...

    African Journals Online (AJOL)

    Uncoupling protein-2 (UCP2) regulates insulin secretion and may play an important role in linking obesity to diabetes type 2 (T2D) that represents a major public health problem in Saudi Arabia. The present study aimed to evaluate the association between the 45-bp insertion/deletion (ins/del) in 3'UTR exon 8 within the ...

  10. Major Links. (United States)

    Henderson, Tona


    Provides electronic mail addresses for resources and discussion groups related to the following academic majors: art, biology, business, chemistry, computer science, economics, health sciences, history, literature, math, music, philosophy, political science, psychology, sociology, and theater. (AEF)

  11. Major Roads (United States)

    Minnesota Department of Natural Resources — This data set contains roadway centerlines for major roads (interstates and trunk highways) found on the USGS 1:24,000 mapping series. These roadways are current...

  12. A Novel Dimeric Inhibitor Targeting Beta2GPI in Beta2GPI/Antibody Complexes Implicated in Antiphospholipid Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    A Kolyada; C Lee; A De Biasio; N Beglova


    {beta}2GPI is a major antigen for autoantibodies associated with antiphospholipid syndrome (APS), an autoimmune disease characterized by thrombosis and recurrent pregnancy loss. Only the dimeric form of {beta}2GPI generated by anti-{beta}2GPI antibodies is pathologically important, in contrast to monomeric {beta}2GPI which is abundant in plasma. We created a dimeric inhibitor, A1-A1, to selectively target {beta}2GPI in {beta}2GPI/antibody complexes. To make this inhibitor, we isolated the first ligand-binding module from ApoER2 (A1) and connected two A1 modules with a flexible linker. A1-A1 interferes with two pathologically important interactions in APS, the binding of {beta}2GPI/antibody complexes with anionic phospholipids and ApoER2. We compared the efficiency of A1-A1 to monomeric A1 for inhibition of the binding of {beta}2GPI/antibody complexes to anionic phospholipids. We tested the inhibition of {beta}2GPI present in human serum, {beta}2GPI purified from human plasma and the individual domain V of {beta}2GPI. We demonstrated that when {beta}2GPI/antibody complexes are formed, A1-A1 is much more effective than A1 in inhibition of the binding of {beta}2GPI to cardiolipin, regardless of the source of {beta}2GPI. Similarly, A1-A1 strongly inhibits the binding of dimerized domain V of {beta}2GPI to cardiolipin compared to the monomeric A1 inhibitor. In the absence of anti-{beta}2GPI antibodies, both A1-A1 and A1 only weakly inhibit the binding of pathologically inactive monomeric {beta}2GPI to cardiolipin. Our results suggest that the approach of using a dimeric inhibitor to block {beta}2GPI in the pathological multivalent {beta}2GPI/antibody complexes holds significant promise. The novel inhibitor A1-A1 may be a starting point in the development of an effective therapeutic for antiphospholipid syndrome.

  13. Molecular characterization of NRXN1 deletions from 19,263 clinical microarray cases identifies exons important for neurodevelopmental disease expression (United States)

    Lowther, Chelsea; Speevak, Marsha; Armour, Christine M.; Goh, Elaine S.; Graham, Gail E.; Li, Chumei; Zeesman, Susan; Nowaczyk, Malgorzata J.M.; Schultz, Lee-Anne; Morra, Antonella; Nicolson, Rob; Bikangaga, Peter; Samdup, Dawa; Zaazou, Mostafa; Boyd, Kerry; Jung, Jack H.; Siu, Victoria; Rajguru, Manjulata; Goobie, Sharan; Tarnopolsky, Mark A.; Prasad, Chitra; Dick, Paul T.; Hussain, Asmaa S.; Walinga, Margreet; Reijenga, Renske G.; Gazzellone, Matthew; Lionel, Anath C.; Marshall, Christian R.; Scherer, Stephen W.; Stavropoulos, Dimitri J.; McCready, Elizabeth; Bassett, Anne S.


    Purpose The purpose of the current study was to assess the penetrance of NRXN1 deletions. Methods We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant CNVs was used as a proxy to estimate the relative penetrance of NRXN1 deletions. Results We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability, significantly greater than in controls [OR=8.14 (95% CI 2.91–22.72), p< 0.0001)]. Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3′ end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5′ NRXN1 deletion [OR=7.47 (95% CI 2.36–23.61), p=0.0006]. The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (p=0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV, a two-fold greater prevalence than for exonic NRXN1 deletion cases (p=0.0035). Conclusions The results support the importance of exons near the 5′ end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes. PMID:27195815

  14. BetaShape: A new code for improved analytical calculations of beta spectra

    Directory of Open Access Journals (Sweden)

    Mougeot Xavier


    Full Text Available The new code BetaShape has been developed in order to improve the nuclear data related to beta decays. An analytical model was considered, except for the relativistic electron wave functions, for ensuring fast calculations. Output quantities are mean energies, log ft values and beta and neutrino spectra for single and multiple transitions. The uncertainties from the input parameters, read from an ENSDF file, are propagated. A database of experimental shape factors is included. A comparison over the entire ENSDF database with the standard code currently used in nuclear data evaluations shows consistent results for the vast majority of the transitions and highlights the improvements that can be expected with the use of BetaShape.


    Directory of Open Access Journals (Sweden)

    G. A. Tsaur


    Full Text Available We assessed the prognostic significance of IKZF1 gene deletions in 141 pediatric patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL  on Russian multicenter trial in pediatric clinics of Ekaterinburg and Orenburg. IKZF1 deletions were estimated by multiplex ligation-dependent probe amplification. IKZF1 deletions were revealed in 15 (10.6 % patients. IKZF1 deletions were associated with age older than 10 years (p = 0.007, initial white blood cell count higher than 30 × 109/l (p = 0.003, t(9;22(q34.q11 (p = 0.003 and delayed blast clearance: М3 status of bone marrow at day 15 of remission induction (p = 0.003, lack of hematological remission at day 36 (p < 0.001 and high levels of minimal residual disease at days 15, 36 and 85 (p = 0.014; p < 0.001; p = 0.001 correspondingly. Patients with IKZF1 deletions had significantly lower event-free survival (EFS (0.30 ± 0.15 vs 0.89 ± 0.03; p < 0.001 and overall survival (OS (0.44 ± 0.19 vs 0.93 ± 0.02; p < 0.001, while cumulative incidence of relapse was higher (0.67 ± 0.18 vs 0.07 ± 0.02; p < 0.001. In the multivariate analysis IKZF1 deletions were associated with decreased EFS (hazard ratio (HR 4.755; 95 % confidence interval (CI 1.856–12.185; p = 0.001, and OS (HR 4.208; 95 % CI 1.322–13.393; p = 0.015, but increased relapse risk (HR 9,083; 95 % CI 3.119–26.451; p < 0.001. IKZF1 deletions retained their prognostic significance in the intermediate risk group patients (p < 0.001, but not in standard or high-risk groups. Majority of IKZF1 deletions – 12 (80 % of 15 – were revealed in the “B-other” group (n = 83. In this cohort of patients IKZF1 deletions led to inferior EFS (HR 6.172; 95 % CI 1.834–20.767; p = 0.003 and higher relapse rate (HR 16.303; 95 % CI 3.324–79.965; p = 0.015. Thus, our results showed that IKZF1 deletions are independent risk factor in BCP-ALL patients.

  16. Inhibition of Breast Cancer Metastasis by Heregulin-Beta 1

    National Research Council Canada - National Science Library

    Yu, Dihua


    The major goal of this Idea proposal is to determine whether and how HRG-Beta1 inhibits breast cancer metastasis and to identify the functional domains that are sufficient for inhibition of breast cancer metastasis...

  17. Genetics Home Reference: 17q12 deletion syndrome (United States)

    ... with 17q12 deletion syndrome have delayed development (particularly speech and language delays), intellectual disability, or behavioral or psychiatric disorders. Behavioral and psychiatric conditions that have been reported in people with 17q12 deletion syndrome include autism ...

  18. Conformational changes of the amyloid beta-peptide (1-40) adsorbed on solid surfaces

    NARCIS (Netherlands)

    Giacomelli, CE; Norde, W


    The conformational change of the 39-43 residues of the amyloid beta-peptide (A beta) toward a beta-sheet enriched state promotes self-aggregation of the peptide molecules and constitutes the major peptide component of the amyloid plaques in Alzheimer patients. The crucial question behind the

  19. Conformational changes of the amyloid beta-peptide (1-40) adsorbed on solid surfaces

    NARCIS (Netherlands)

    Giacomelli, C.E.; Norde, W.


    The conformational change of the 39-43 residues of the amyloid beta -peptide (A beta) toward a beta -sheet enriched state promotes self-aggregation of the peptide molecules and constitutes the major peptide component of the amyloid plaques in Alzheimer patients. The crucial question behind the

  20. Probabilistic deletion of copies of linearly independent quantum states

    International Nuclear Information System (INIS)

    Feng Jian; Gao Yunfeng; Wang Jisuo; Zhan Mingsheng


    We show that each of two copies of the nonorthogonal states randomly selected from a certain set S can be probabilistically deleted by a general unitary-reduction operation if and only if the states are linearly independent. We derive a tight bound on the best possible deleting efficiencies. These results for 2→1 probabilistic deleting are also generalized into the case of N→M deleting (N,M positive integers and N>M)

  1. Boosted beta regression.

    Directory of Open Access Journals (Sweden)

    Matthias Schmid

    Full Text Available Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1. Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures.

  2. Deletion Mutations in an Australian Series of HNPCC Patients

    Directory of Open Access Journals (Sweden)

    McPhillips Mary


    Full Text Available Abstract Hereditary non polyposis colorectal cancer (HNPCC is characterized by the presence of early onset colorectal cancer and other epithelial malignancies. The genetic basis of HNPCC is a deficiency in DNA mismatch repair, which manifests itself as DNA microsatellite instability in tumours. There are four genes involved in DNA mismatch repair that have been linked to HNPCC; these include hMSH2, hMLH1, hMSH6 and hPMS2. Of these four genes hMLH1 and hMSH2 account for the majority of families diagnosed with the disease. Notwithstanding, up to 40 percent of families do not appear to harbour a change in either hMSH2 or hMLH1 that can be detected using standard screening procedures such as direct DNA sequencing or a variety of methods all based on a heteroduplex analysis. In this report we have screened a series of 118 probands that all have the clinical diagnosis of HNPCC for medium to large deletions by the Multiplex Ligation-Dependent Probe Amplification assay (MLPA to determine the frequency of this type of mutation. The results indicate that a significant proportion of Australian HNPCC patients harbour deletion or duplication mutations primarily in hMSH2 but also in hMLH1.

  3. Files synchronization from a large number of insertions and deletions (United States)

    Ellappan, Vijayan; Kumari, Savera


    Synchronization between different versions of files is becoming a major issue that most of the applications are facing. To make the applications more efficient a economical algorithm is developed from the previously used algorithm of “File Loading Algorithm”. I am extending this algorithm in three ways: First, dealing with non-binary files, Second backup is generated for uploaded files and lastly each files are synchronized with insertions and deletions. User can reconstruct file from the former file with minimizing the error and also provides interactive communication by eliminating the frequency without any disturbance. The drawback of previous system is overcome by using synchronization, in which multiple copies of each file/record is created and stored in backup database and is efficiently restored in case of any unwanted deletion or loss of data. That is, to introduce a protocol that user B may use to reconstruct file X from file Y with suitably low probability of error. Synchronization algorithms find numerous areas of use, including data storage, file sharing, source code control systems, and cloud applications. For example, cloud storage services such as Drop box synchronize between local copies and cloud backups each time users make changes to local versions. Similarly, synchronization tools are necessary in mobile devices. Specialized synchronization algorithms are used for video and sound editing. Synchronization tools are also capable of performing data duplication.

  4. 78 FR 29119 - Procurement List; Additions and Deletion (United States)


    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to and Deletion from the Procurement List. SUMMARY: This action adds products and services to the... Activity: Washington Headquarters Services (WHS), Acquisition Directorate, Washington, DC. Deletion On 4/5...

  5. 5 CFR 1631.17 - Deletion of exempted information. (United States)


    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Deletion of exempted information. 1631.17... Deletion of exempted information. Where requested records contain matters which are exempted under 5 U.S.C... disclosed by the Board with deletions. To each such record, the Board shall attach a written justification...

  6. 75 FR 56995 - Procurement List Proposed Additions and Deletion (United States)


    ... Additions and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to and Deletion From the Procurement List. SUMMARY: The Committee is proposing to add... aggregated by the Defense Logistics Agency Troop Support, Philadelphia, PA. Deletion Regulatory Flexibility...

  7. 5 CFR 2502.18 - Deletion of exempted information. (United States)


    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Deletion of exempted information. 2502.18... Charges for Search and Reproduction § 2502.18 Deletion of exempted information. Where requested records... the remainder of the records, they shall be disclosed by the Office with deletions. To each such...

  8. 78 FR 75912 - Procurement List; Addition and Deletion (United States)


    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Addition to and deletion from the Procurement List. SUMMARY: This action adds a service to the Procurement...: General Services Administration, Fort Worth, TX Deletion On 11/1/2013 (78 FR 65618), the Committee for...

  9. 78 FR 27369 - Procurement List; Additions and Deletion (United States)


    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to and Deletion from the Procurement List. SUMMARY: This action adds products to the Procurement..., Philadelphia, PA. Deletion On 4/5/2013 (78 FR 20622-20623), the Committee for Purchase From People Who Are...

  10. 75 FR 7450 - Procurement List: Proposed Addition and Deletion (United States)


    ... Addition and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed addition to and deletion from Procurement List. SUMMARY: The Committee is proposing to add to the... W6BA ACA, FT CARSON, COLORADO. Deletion Regulatory Flexibility Act Certification I certify that the...

  11. 77 FR 20795 - Procurement List Proposed Addition and Deletion (United States)


    ... Addition and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Addition to and Deletion from the Procurement List. SUMMARY: The Committee is proposing to add a.... Deletion Regulatory Flexibility Act Certification I certify that the following action will not have a...

  12. 36 CFR 1275.58 - Deletion of restricted portions. (United States)


    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Deletion of restricted... HISTORICAL MATERIALS OF THE NIXON ADMINISTRATION Access by the Public § 1275.58 Deletion of restricted... materials after the deletion of the portions which are restricted under this § 1275.50 or § 1275.52. ...

  13. 75 FR 69638 - Procurement List; Additions and Deletion (United States)


    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to and deletion from the Procurement List. SUMMARY: This action adds products and a service to the...), DENVER, CO. Deletion On 9/17/2010 (75 FR 56995-56996), the Committee for Purchase From People Who Are...

  14. 76 FR 60810 - Procurement List; Proposed Additions and Deletion (United States)


    ... Additions and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to and Deletion from the Procurement List. SUMMARY: The Committee is proposing to add... Activity: Department of Energy, Idaho Operations Office, Idaho Falls, ID. DELETION Regulatory Flexibility...

  15. 44 CFR 5.27 - Deletion of identifying details. (United States)


    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Deletion of identifying... Availability of General Agency Information, Rules, Orders, Policies, and Similar Material § 5.27 Deletion of..., interpretation, or staff manual or instruction. However, the justification for each deletion will be explained...

  16. 29 CFR 1610.20 - Deletion of exempted matters. (United States)


    ... 29 Labor 4 2010-07-01 2010-07-01 false Deletion of exempted matters. 1610.20 Section 1610.20 Labor... Production or Disclosure Under 5 U.S.C. 552 § 1610.20 Deletion of exempted matters. Where requested records... the remainder of the records, they shall be disclosed by the Commission with deletions. To each such...

  17. 49 CFR 7.6 - Deletion of identifying detail. (United States)


    ... 49 Transportation 1 2010-10-01 2010-10-01 false Deletion of identifying detail. 7.6 Section 7.6... To Be Made Public by DOT § 7.6 Deletion of identifying detail. Whenever it is determined to be... the deletion will accompany the record published or made available for inspection. ...

  18. 76 FR 5142 - Procurement List; Additions and Deletion (United States)


    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to and deletion from the Procurement List. SUMMARY: This action adds services to the Procurement.... Contracting Activity: Department of Transportation, Federal Aviation Administration, Jamaica, NY. Deletion On...

  19. Genetics Home Reference: proximal 18q deletion syndrome (United States)

    ... characteristic features. Most cases of proximal 18q deletion syndrome are the result of a new (de novo) deletion and are not inherited from a ... J, Fox PT, Stratton RF, Perry B, Hale DE. Recurrent interstitial deletions of proximal 18q: a new syndrome involving expressive speech delay. Am J Med Genet ...

  20. Characterization of five partial deletions of the factor VIII gene

    International Nuclear Information System (INIS)

    Youssoufian, H.; Antonarakis, S.E.; Aronis, S.; Tsiftis, G.; Phillips, D.G.; Kazazian, H.H. Jr.


    Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. By using cloned DNA probes, the authors have characterized the following five different partial deletions of the factor VIII gene from a panel of 83 patients with hemophilia A: (i) a 7-kilobase (kb) deletion that eliminates exon 6; (ii) a 2.5-kb deletion that eliminates 5' sequences of exon 14; (iii) a deletion of at least 7 kb that eliminates exons 24 and 25; (iv) a deletion of at least 16 kb that eliminates exons 23-25; and (v) a 5.5-kb deletion that eliminates exon 22. The first four deletions are associated with severe hemophilia A. By contrast, the last deletion is associated with moderate disease, possibly because of in-frame splicing from adjacent exons. None of those patients with partial gene deletions had circulating inhibitors to factor VIII. One deletion occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of the maternal grandfather. These observations demonstrate that de novo deletions of X-linked genes can occur in either male or female gametes

  1. beta. -Amyloid gene dosage in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Murdoch, G H; Manuelidis, L; Kim, J H; Manuelidis, E E


    The 4-5 kd amyloid ..beta..-peptide is a major constituent of the characteristic amyloid plaque of Alzheimer's disease. It has been reported that some cases of sporatic Alzheimer's disease are associated with at least a partial duplication of chromosome 21 containing the gene corresponding to the 695 residue precursor of this peptide. To contribute to an understanding of the frequency to such a duplication event in the overall Alzheimer's population, the authors have determined the gene dosage of the ..beta..-amyloid gene in this collection of cases. All cases had a clinical diagnosis of Alzheimer's confirmed neuropathologically. Each Alzheimer's case had an apparent normal diploid ..beta..-amyloid gene dosage, while control Down's cases had the expected triploid dosage. Thus partial duplication of chromosome 21 may be a rare finding in Alzheimer's disease. Similar conclusions were just reported in several studies of the Harvard Alzheimer collection.

  2. Screening of Dystrophin Gene Deletions in Egyptian Patients with DMD/BMD Muscular Dystrophies

    Directory of Open Access Journals (Sweden)

    Laila K. Effat


    Full Text Available Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are allelic disorders caused by mutations within the dystrophin gene. Our study has identified 100 Egyptian families collected from the Human Genetics Clinic, National Research Center, Cairo. All cases were subjected to complete clinical evaluation pedigree analysis, electromyography studies, estimation of serum creatine phosphokinase enzyme (CPK levels and DNA analysis. Multiplex PCR using 18 pairs of specific primers were used for screening of deletion mutations within the dystrophin gene. A frequency of 55% among the families. Sixty per cent of detected deletions involved multiple exons spanning the major or the minor hot spot of the dystrophin gene. The remainder 40% which mainly involved exon 45. Comparing these findings with frequencies of other countries it was found that our figures fall within the reported range of 40%– for deletions. The distribution of deletions in our study and other different studies was variable and specific ethnic differences do not apparently account for specific deletions. In addition this study concluded that employment of the 18 exon analysis is a cost effective and a highly accurate (97% to launch a nationwide program.

  3. Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome (United States)

    Cheung, Evelyn Ning Man; George, Susan R.; Andrade, Danielle M.; Chow, Eva W. C.; Silversides, Candice K.; Bassett, Anne S.


    Purpose Hypocalcemia is a common endocrinological condition in 22q11.2 deletion syndrome. Neonatal hypocalcemia may affect neurodevelopment. We hypothesized that neonatal hypocalcemia would be associated with rare, more severe forms of intellectual disability in 22q11.2 deletion syndrome. Methods We used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease, e.g., interrupted aortic arch, in 149 adults with 22q11.2 deletion syndrome. Ten subjects had moderate-to-severe intellectual disability. Results The model was highly significant (P < 0.0001), showing neonatal seizures (P = 0.0018) and neonatal hypocalcemia (P = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with neonatal hypocalcemia in the entire sample (P < 0.0001), regardless of intellectual level. There was no evidence for the association of moderate- to-severe intellectual disability with other factors such as major structural brain malformations in this sample. Conclusion The results suggest that neonatal seizures may increase the risk for more severe intellectual deficits in 22q11.2 deletion syndrome, likely mediated by neonatal hypocalcemia. Neonatal hypocalcemia often remains unrecognized until the postseizure period, when damage to neurons may already have occurred. These findings support the importance of early recognition and treatment of neonatal hypocalcemia and potentially neonatal screening for 22q11.2 deletions. PMID:23765047

  4. Selective neuronal PTEN deletion: can we take the brakes off of growth without losing control?

    Directory of Open Access Journals (Sweden)

    Erin A Gutilla


    Full Text Available The limited ability for injured adult axons to regenerate is a major cause for limited functional recovery after injury to the nervous system, motivating numerous efforts to uncover mechanisms capable of enhancing regeneration potential. One promising strategy involves deletion or knockdown of the phosphatase and tensin (PTEN gene. Conditional genetic deletion of PTEN before, immediately following, or several months after spinal cord injury enables neurons of the corticospinal tract (CST to regenerate their axons across the lesion, which is accompanied by enhanced recovery of skilled voluntary motor functions mediated by the CST. Although conditional genetic deletion or knockdown ofPTEN in neurons enables axon regeneration, PTEN is a well-known tumor suppressor and mutations of the PTEN gene disrupt brain development leading to neurological abnormalities including macrocephaly, seizures, and early mortality. The long-term consequences of manipulating PTEN in the adult nervous system, as would be done for therapeutic intervention after injury, are only now being explored. Here, we summarize evidence indicating that long-term deletion of PTEN in mature neurons does not cause evident pathology; indeed, cortical neurons that have lived without PTEN for over 1 year appear robust and healthy. Studies to date provide only a first look at potential negative consequences of PTEN deletion or knockdown, but the absence of any detectable neuropathology supports guarded optimism that interventions to enable axon regeneration after injury are achievable.

  5. An environment-mediated quantum deleter

    International Nuclear Information System (INIS)

    Srikanth, R.; Banerjee, Subhashish


    Environment-induced decoherence presents a great challenge to realizing a quantum computer. We point out the somewhat surprising fact that decoherence can be useful, indeed necessary, for practical quantum computation, in particular, for the effective erasure of quantum memory in order to initialize the state of the quantum computer. The essential point behind the deleter is that the environment, by means of a dissipative interaction, furnishes a contractive map towards a pure state. We present a specific example of an amplitude damping channel provided by a two-level system's interaction with its environment in the weak Born-Markov approximation. This is contrasted with a purely dephasing, non-dissipative channel provided by a two-level system's interaction with its environment by means of a quantum nondemolition interaction. We point out that currently used state preparation techniques, for example using optical pumping, essentially perform as quantum deleters

  6. Ins1 Cre knock-in mice for beta cell-specific gene recombination


    Thorens Bernard; Tarussio David; Maestro Miguel Angel; Maestro Miguel Angel; Rovira Meritxell; Rovira Meritxell; Heikkilä Eija; Ferrer Jorge; Ferrer Jorge; Ferrer Jorge


    Aims/hypothesis Pancreatic beta cells play a central role in the control of glucose homeostasis by secreting insulin to stimulate glucose uptake by peripheral tissues. Understanding the molecular mechanisms that control beta cell function and plasticity has critical implications for the pathophysiology and therapy of major forms of diabetes. Selective gene inactivation in pancreatic beta cells, using the Cre-lox system, is a powerful approach to assess the role of particular genes in beta cel...

  7. Labelling of. beta. -endorphin (. beta. -END) and. beta. -lipotropin (. beta. -LPH) by /sup 125/I

    Energy Technology Data Exchange (ETDEWEB)

    Deby-Dupont, G.; Joris, J.; Franchimont, P. (Universite de Liege (Belgique)); Reuter, A.M.; Vrindts-Gevaert, Y. (Institut des Radioelements, Fleurus (Belgique))


    5 of human ..beta..-endorphin were labelled with 2 mCi /sup 125/I by the chloramine T technique. After two gel filtrations on Sephadex G-15 and on Sephadex G-50 in phosphate buffer with EDTA, Trasylol and mercapto-ethanol, a pure tracer was obtained with a specific activity about 150 at + 4/sup 0/C, the tracer remained utilizable for 30 days without loss of immunoreactivity. The labelling with lactoperoxydase and the use of another gel filtration method (filtration on Aca 202) gave a /sup 125/I ..beta..-END tracer with the same immunoreactivity. The binding of this tracer to the antibody of an anti-..beta..-END antiserum diluted at 1/8000 was 32% with a non specific binding of 2%. 5 of human ..beta..-lipotropin were labelled with 0.5 mCi /sup 125/I by the lactoperoxydase method. After two gel filtrations on Sephadex G-25 and on Sephadex G-75 in phosphate buffer with EDTA, Trasylol and mercapto-ethanol, a pure tracer with a specific activity of 140 was obtained. It remained utilizable for 30 days when kept at + 4/sup 0/C. Gel filtration on Aca 202 did not give good purification, while gel filtration on Aca 54 was good but slower than on Sephadex G-75. The binding to antibody in absence of unlabelled ..beta..-LPH was 32% for an anti-..beta..-LPH antiserum diluted at 1/4000. The non specific binding was 2.5%.

  8. Plasma beta HCG determination

    International Nuclear Information System (INIS)

    Amaral, L.B.D.; Pinto, J.C.M.; Linhares, E.; Linhares, Estevao


    There are three important indications for the early diagnosis of pregnancy through the determination of the beta sub-unit of chorionic gonadotrophin using radioimmunoassay: 1) some patient's or doctor's anxiety to discover the problem; 2) when it will be necessary to employ diagnostic or treatment procedures susceptible to affect the ovum; and 3) in the differential diagnosis of amenorrhoea, uterine hemorrhage and abdominal tumors. Other user's are the diagnosis of missed absortion, and the diagnosis and follow-up of chrorioncarcinoma. The AA. studied 200 determinations of plasma beta-HCG, considering the main difficulties occuring in the clinical use of this relevant laboratory tool in actual Obstetrics. (author) [pt

  9. Relation between the 2{nu}{beta}{beta} and 0{nu}{beta}{beta} nuclear matrix elements

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, Petr [Kellogg Radiation Laboratory, Caltech, Pasadena, CA 91125 (United States); Simkovic, Fedor [Department of Nuclear Physics and Biophysics, Comenius University, Mlynska dolina F1, SK-84248 Bratislava (Slovakia)


    A formal relation between the GT part of the nuclear matrix elements M{sub GT}{sup 0{nu}} of 0{nu}{beta}{beta} decay and the closure matrix elements M{sub cl}{sup 2{nu}} of 2{nu}{beta}{beta} decay is established. This relation is based on the integral representation of these quantities in terms of their dependence on the distance r between the two nucleons undergoing transformation. We also discuss the difficulties in determining the correct values of the closure 2{nu}{beta}{beta} decay matrix elements.

  10. Synergistic effects of high fat feeding and apolipoprotein E deletion on enterocytic amyloid-beta abundance

    Directory of Open Access Journals (Sweden)

    Dhaliwal Satvinder S


    Full Text Available Abstract Background Amyloid-β (Aβ, a key protein found in amyloid plaques of subjects with Alzheimer's disease is expressed in the absorptive epithelial cells of the small intestine. Ingestion of saturated fat significantly enhances enterocytic Aβ abundance whereas fasting abolishes expression. Apolipoprotein (apo E has been shown to directly modulate Aβ biogenesis in liver and neuronal cells but it's effect in enterocytes is not known. In addition, apo E modulates villi length, which may indirectly modulate Aβ as a consequence of differences in lipid absorption. This study compared Aβ abundance and villi length in wild-type (WT and apo E knockout (KO mice maintained on either a low-fat or high-fat diet. Wild-type C57BL/6J and apo E KO mice were randomised for six-months to a diet containing either 4% (w/w unsaturated fats, or chow comprising 16% saturated fats and 1% cholesterol. Quantitative immunohistochemistry was used to assess Aβ abundance in small intestinal enterocytes. Apo E KO mice given the low-fat diet had similar enterocytic Aβ abundance compared to WT controls. Results The saturated fat diet substantially increased enterocytic Aβ in WT and in apo E KO mice, however the effect was greater in the latter. Villi height was significantly greater in apo E KO mice than for WT controls when given the low-fat diet. However, WT mice had comparable villi length to apo E KO when fed the saturated fat and cholesterol enriched diet. There was no effect of the high-fat diet on villi length in apo E KO mice. Conclusion The findings of this study are consistent with the notion that lipid substrate availability modulates enterocytic Aβ. Apo E may influence enterocytic lipid availability by modulating absorptive capacity.

  11. Clinical implications of cytosine deletion of exon 5 of P53 gene in non small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Rashid Mir


    Full Text Available Aim: Lung cancer is considered to be the most common cancer in the world. In humans, about 50% or more cancers have a mutated tumor suppressor p53 gene thereby resulting in accumulation of p53 protein and losing its function to activate the target genes that regulate the cell cycle and apoptosis. Extensive research conducted in murine cancer models with activated p53, loss of p53, or p53 missense mutations have facilitated researchers to understand the role of this key protein. Our study was aimed to evaluate the frequency of cytosine deletion in nonsmall cell lung cancer (NSCLC patients. Methods: One hundred NSCLC patients were genotyped for P53 (exon5, codon168 cytosine deletion leading to loss of its function and activate the target genes by allele-specific polymerase chain reaction. The P53 cytosine deletion was correlated with all the clinicopathological parameters of the patients. Results and Analysis: 59% cases were carrying P53 cytosine deletion. Similarly, the significantly higher incidence of cytosine deletion was reported in current smokers (75% in comparison to exsmoker and nonsmoker. Significantly higher frequency of cytosine deletion was reported in adenocarcinoma (68.08% than squamous cell carcinoma (52.83%. Also, a significant difference was reported between p53 cytosine deletion and metastasis (64.28%. Further, the majority of the cases assessed for response carrying P53 cytosine deletion were found to show faster disease progression. Conclusion: The data suggests that there is a significant association of the P53 exon 5 deletion of cytosine in codon 168 with metastasis and staging of the disease.

  12. Induced nuclear beta decay

    International Nuclear Information System (INIS)

    Reiss, H.R.


    Certain nuclear beta decay transitions normally inhibited by angular momentum or parity considerations can be induced to occur by the application of an electromagnetic field. Such decays can be useful in the controlled production of power, and in fission waste disposal

  13. Trichoderma .beta.-glucosidase (United States)

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian


    The present invention provides a novel .beta.-glucosidase nucleic acid sequence, designated bgl3, and the corresponding BGL3 amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding BGL3, recombinant BGL3 proteins and methods for producing the same.

  14. Applied Beta Dosimetry

    International Nuclear Information System (INIS)

    Rich, B.L.


    Measurements of beta and/or nonpenetrating exposure results is complicated and past techniques and capabilities have resulted in significant inaccuracies in recorded results. Current developments have resulted in increased capabilities which make the results more accurate and should result in less total exposure to the work force. Continued development of works in progress should provide equivalent future improvements

  15. Beta thalassemia - a review

    Directory of Open Access Journals (Sweden)

    R Jha


    Full Text Available Thalassemia is a globin gene disorder that results in a diminished rate of synthesis of one or more of the globin chains. About 1.5% of the global population (80 to 90 million people are carriers of beta Thalassemia. More than 200 mutations are described in beta thalassemia. However not all mutations are common in different ethnic groups. The only effective way to reduce burden of thalassemia is to prevent birth of homozygotes. Diagnosis of beta thalassemia can be done by fetal DNA analysis for molecular defects of beta thalassemia or by fetal blood analysis. Hematopoietic stem cell transplantation is the only available curative approach for Thalassemia. Many patients with thalassemia in underdeveloped nations die in childhood or adolescence. Programs that provide acceptable care, including transfusion of safe blood and supportive therapy including chelation must be established.DOI: Journal of Pathology of Nepal; Vol.4,No. 8 (2014 663-671

  16. Double Beta Decay Experiments

    International Nuclear Information System (INIS)

    Piepke, A.


    The experimental observation of neutrino oscillations and thus neutrino mass and mixing gives a first hint at new particle physics. The absolute values of the neutrino mass and the properties of neutrinos under CP-conjugation remain unknown. The experimental investigation of the nuclear double beta decay is one of the key techniques for solving these open problems

  17. Beta cell adaptation in pregnancy

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis


    Pregnancy is associated with a compensatory increase in beta cell mass. It is well established that somatolactogenic hormones contribute to the expansion both indirectly by their insulin antagonistic effects and directly by their mitogenic effects on the beta cells via receptors for prolactin...... and growth hormone expressed in rodent beta cells. However, the beta cell expansion in human pregnancy seems to occur by neogenesis of beta cells from putative progenitor cells rather than by proliferation of existing beta cells. Claes Hellerström has pioneered the research on beta cell growth for decades...... in the expansion of the beta cell mass in human pregnancy, and the relative roles of endocrine factors and nutrients....

  18. High-resolution melting analysis for prenatal diagnosis of beta-thalassemia in northern Thailand. (United States)

    Charoenkwan, Pimlak; Sirichotiyakul, Supatra; Phusua, Arunee; Suanta, Sudjai; Fanhchaksai, Kanda; Sae-Tung, Rattika; Sanguansermsri, Torpong


    High-resolution melting (HRM) analysis is a rapid mutation analysis which assesses the pattern of reduction of fluorescence signal after subjecting the amplified PCR product with saturated fluorescence dye to an increasing temperature. We used HRM analysis for prenatal diagnosis of beta-thalassemia disease in northern Thailand. Five PCR-HRM protocols were used to detect point mutations in five different segments of the beta-globin gene, and one protocol to detect the 3.4 kb beta-globin deletion. We sought to characterize the mutations in carriers and to enable prenatal diagnosis in 126 couples at risk of having a fetus with beta-thalassemia disease. The protocols identified 18 common mutations causing beta-thalassemia, including the rare codon 132 (A-T) mutation. Each mutation showed a specific HRM pattern and all results were in concordance with those from direct DNA sequencing or gap-PCR methods. In cases of beta-thalassemia disease resulting from homozygosity for a mutation or compound heterozygosity for two mutations on the same amplified segment, the HRM patterns were different to those of a single mutation and were specific for each combination. HRM analysis is a simple and useful method for mutation identification in beta-thalassemia carriers and prenatal diagnosis of beta-thalassemia in northern Thailand.

  19. Chromosomal deletion unmasking a recessive disease: 22q13 deletion syndrome and metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    Bisgaard, A-M; Kirchhoff, M; Nielsen, J E


    A deletion on one chromosome and a mutant allele on the other may cause an autosomal recessive disease. We report on two patients with mental retardation, dysmorphic features and low catalytic activity of arylsulfatase A. One patient had a pathogenic mutation in the arylsulfatase A gene (ARSA......) and succumbed to metachromatic leukodystrophy (MLD). The other patient had a pseudoallele, which does not lead to MLD. The presenting clinical features and low arylsulfatase A activity were explained, in each patients, by a deletion of 22q13 and, thereby, of one allele of ARSA....

  20. Misleading Betas: An Educational Example (United States)

    Chong, James; Halcoussis, Dennis; Phillips, G. Michael


    The dual-beta model is a generalization of the CAPM model. In the dual-beta model, separate beta estimates are provided for up-market and down-market days. This paper uses the historical "Anscombe quartet" results which illustrated how very different datasets can produce the same regression coefficients to motivate a discussion of the…

  1. Effect of gamma rays at the dihydrofolate reductase locus: deletions and inversions

    International Nuclear Information System (INIS)

    Urlaub, G.; Mitchell, P.J.; Kas, E.; Chasin, L.A.; Funanage, V.L.; Myoda, T.T.; Hamlin, J.


    A series 11 gamma-ray-induced mutants at the dihydrofolate reductase (dhfr) locus in Chinese hamster ovary cells has been examined for the types of DNA sequence change brought about by this form of ionizing radiation. All 11 mutants were found to have suffered major structural changes affecting the dhfr gene. In eight of the mutants, all or part of the dhfr gene has been deleted. The extent of these deletions was examined in seven of these mutants and, for comparison, in two deletion mutants that were induced by UV irradiation. For this purpose, probes from an overlapping set of cosmids that span 210 kb of DNA in this region were used. Three of seven gamma-ray-induced mutants and one UV-induced mutant were shown to have deleted the entire 210-kb region. In the remaining mutants, endpoints ranging from within the dhfr gene to 100 kb downstream were observed. No upstream endpoints were detected, so that an upper limit on the size of these large deletions could not be assigned. Three of the 11 gamma-ray-induced mutants contained an interruption in the dhfr gene without any detectable loss of sequence. Restriction analysis of these interrupted mutants showed that at least 8-14 kb of foreign DNA sequence became joined to the gene at the point of disruption. Cytogenetic analysis of these mutants showed that in two cases an inversion of the banding pattern on chromosome Z-2 had taken place. The inverted dhfr mutants contain very low amounts of dhfr RNA sequences, and the 5' end of an inversion mutant gene exhibits the same pattern of DNA methylation and DNase I-hypersensitivity as the wild-type gene. Our results suggest that ionizing radiation causes primarily, if not exclusively, large deletions and inversions in mammalian cells

  2. Interaction with beta-arrestin determines the difference in internalization behavor between beta1- and beta2-adrenergic receptors. (United States)

    Shiina, T; Kawasaki, A; Nagao, T; Kurose, H


    The beta(1)-adrenergic receptor (beta(1)AR) shows the resistance to agonist-induced internalization. As beta-arrestin is important for internalization, we examine the interaction of beta-arrestin with beta(1)AR with three different methods: intracellular trafficking of beta-arrestin, binding of in vitro translated beta-arrestin to intracellular domains of beta(1)- and beta(2)ARs, and inhibition of betaAR-stimulated adenylyl cyclase activities by beta-arrestin. The green fluorescent protein-tagged beta-arrestin 2 translocates to and stays at the plasma membrane by beta(2)AR stimulation. Although green fluorescent protein-tagged beta-arrestin 2 also translocates to the plasma membrane, it returns to the cytoplasm 10-30 min after beta(1)AR stimulation. The binding of in vitro translated beta-arrestin 1 and beta-arrestin 2 to the third intracellular loop and the carboxyl tail of beta(1)AR is lower than that of beta(2)AR. The fusion protein of beta-arrestin 1 with glutathione S-transferase inhibits the beta(1)- and beta(2)AR-stimulated adenylyl cyclase activities, although inhibition of the beta(1)AR-stimulated activity requires a higher concentration of the fusion protein than that of the beta(2)AR-stimulated activity. These results suggest that weak interaction of beta(1)AR with beta-arrestins explains the resistance to agonist-induced internalization. This is further supported by the finding that beta-arrestin can induce internalization of beta(1)AR when beta-arrestin 1 does not dissociate from beta(1)AR by fusing to the carboxyl tail of beta(1)AR.

  3. Writing and deleting single magnetic skyrmions. (United States)

    Romming, Niklas; Hanneken, Christian; Menzel, Matthias; Bickel, Jessica E; Wolter, Boris; von Bergmann, Kirsten; Kubetzka, André; Wiesendanger, Roland


    Topologically nontrivial spin textures have recently been investigated for spintronic applications. Here, we report on an ultrathin magnetic film in which individual skyrmions can be written and deleted in a controlled fashion with local spin-polarized currents from a scanning tunneling microscope. An external magnetic field is used to tune the energy landscape, and the temperature is adjusted to prevent thermally activated switching between topologically distinct states. Switching rate and direction can then be controlled by the parameters used for current injection. The creation and annihilation of individual magnetic skyrmions demonstrates the potential for topological charge in future information-storage concepts.

  4. Transforming growth factor beta stimulation of biglycan gene expression is potentially mediated by sp1 binding factors

    DEFF Research Database (Denmark)

    Heegaard, Anne-Marie; Xie, Zhongjian; Young, Marian Frances


    . In this study, we have investigated the mechanism by which TGF-beta(1), TGF-beta(2) and TGF-beta(3) stimulate biglycan mRNA expression in the osteoblastic cell line MG-63. The cells were transfected with a series of deletional human biglycan promoter constructs and a region in the biglycan 5' DNA was found...... to respond to TGF-beta(1) with increased transcriptional activity in a dose-dependent manner. Also TGF-beta(2) and TGF-beta(3), two structurally highly related TGF-beta isoforms stimulated biglycan transcription. A TGF-beta responsive region was identified within the first 218 bp of the human biglycan...... was abrogated by mithramycin, an inhibitor of Sp1 binding to GC-rich DNA sequences. A mutation in the Sp1 site at -216 to -208 within the -218 biglycan promoter construct substantially diminished the transcriptional up-regulation by TGF-beta(1). Taken together this data shows for the first time that TGF-beta(1...

  5. Low-beta investment strategies


    Korn, Olaf; Kuntz, Laura-Chloé


    This paper investigates investment strategies that exploit the low-beta anomaly. Although the notion of buying low-beta stocks and selling high-beta stocks is natural, a choice is necessary with respect to the relative weighting of high-beta stocks and low-beta stocks in the investment portfolio. Our empirical results for US large-cap stocks show that this choice is very important for the risk-return characteristics of the resulting portfolios and their sensitivities to common risk factors. W...

  6. Neutrophil beta-2 microglobulin: an inflammatory mediator

    DEFF Research Database (Denmark)

    Bjerrum, O W; Nissen, Mogens Holst; Borregaard, N


    Beta-2 microglobulin (beta 2m) constitutes the light invariant chain of HLA class I antigen, and is a constituent of mobilizable compartments of neutrophils. Two forms of beta 2m exist: native beta 2m and proteolytically modified beta 2m (Des-Lys58-beta 2m), which shows alpha mobility in crossed ...

  7. Deletion of P2 promoter of GJB1 gene a cause of Charcot-Marie-Tooth disease. (United States)

    Kulshrestha, R; Burton-Jones, S; Antoniadi, T; Rogers, M; Jaunmuktane, Z; Brandner, S; Kiely, N; Manuel, R; Willis, T


    X-linked Charcot-Marie-Tooth disease (CMT) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene. This gene has nerve specific P2 promoter that work synergistically with SOX10 and EGR2 genes to initiate transcription. Mutation in this region is known to cause Schwann cell dysfunction. A single large family of X linked peripheral neuropathy was identified in our practice. Next generation sequencing for targeted panel assay identified an upstream exon-splicing deletion identified extending from nucleotide c.-5413 to approximately - c.-49. This matches the sequence of 32 nucleotides at positions c.*218-*249 in the 3'UTR downstream of the GJB1 gene. The deleted fragment included the entire P2 promoter region. The deletion segregated with the disease. To our knowledge a deletion of the P2 promoter alone as a cause of CMT has not been reported previously. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Beta and muon decays

    International Nuclear Information System (INIS)

    Galindo, A.; Pascual, P.


    These notes represent a series of lectures delivered by the authors in the Junta de Energia Nuclear, during the Spring term of 1965. They were devoted to graduate students interested in the Theory of Elementary Particles. Special emphasis was focussed into the computational problems. Chapter I is a review of basic principles (Dirac equation, transition probabilities, final state interactions.) which will be needed later. In Chapter II the four-fermion punctual Interaction is discussed, Chapter III is devoted to the study of beta-decay; the main emphasis is given to the deduction of the formulae corresponding to electron-antineutrino correlation, electron energy spectrum, lifetimes, asymmetry of electrons emitted from polarized nuclei, electron and neutrino polarization and time reversal invariance in beta decay. In Chapter IV we deal with the decay of polarized muons with radiative corrections. Chapter V is devoted to an introduction to C.V.C. theory. (Author)

  9. Beta and Gamma Gradients

    DEFF Research Database (Denmark)

    Løvborg, Leif; Gaffney, C. F.; Clark, P. A.


    Experimental and/or theoretical estimates are presented concerning, (i) attenuation within the sample of beta and gamma radiation from the soil, (ii) the gamma dose within the sample due to its own radioactivity, and (iii) the soil gamma dose in the proximity of boundaries between regions...... of differing radioactivity. It is confirmed that removal of the outer 2 mm of sample is adequate to remove influence from soil beta dose and estimates are made of the error introduced by non-removal. Other evaluations include variation of the soil gamma dose near the ground surface and it appears...... that the present practice of avoiding samples above a depth of 0.3 m may be over-cautious...

  10. Beta and muon decays

    Energy Technology Data Exchange (ETDEWEB)

    Galindo, A; Pascual, P


    These notes represent a series of lectures delivered by the authors in the Junta de Energia Nuclear, during the Spring term of 1965. They were devoted to graduate students interested in the Theory of Elementary Particles. Special emphasis was focussed into the computational problems. Chapter I is a review of basic principles (Dirac equation, transition probabilities, final state interactions.) which will be needed later. In Chapter II the four-fermion punctual Interaction is discussed, Chapter III is devoted to the study of beta-decay; the main emphasis is given to the deduction of the formulae corresponding to electron-antineutrino correlation, electron energy spectrum, lifetimes, asymmetry of electrons emitted from polarized nuclei, electron and neutrino polarization and time reversal invariance in beta decay. In Chapter IV we deal with the decay of polarized muons with radiative corrections. Chapter V is devoted to an introduction to C.V.C. theory. (Author)

  11. Whole genome HBV deletion profiles and the accumulation of preS deletion mutant during antiviral treatment (United States)


    Background Hepatitis B virus (HBV), because of its error-prone viral polymerase, has a high mutation rate leading to widespread substitutions, deletions, and insertions in the HBV genome. Deletions may significantly change viral biological features complicating the progression of liver diseases. However, the clinical conditions correlating to the accumulation of deleted mutants remain unclear. In this study, we explored HBV deletion patterns and their association with disease status and antiviral treatment by performing whole genome sequencing on samples from 51 hepatitis B patients and by monitoring changes in deletion variants during treatment. Clone sequencing was used to analyze preS regions in another cohort of 52 patients. Results Among the core, preS, and basic core promoter (BCP) deletion hotspots, we identified preS to have the highest frequency and the most complex deletion pattern using whole genome sequencing. Further clone sequencing analysis on preS identified 70 deletions which were classified into 4 types, the most common being preS2. Also, in contrast to the core and BCP regions, most preS deletions were in-frame. Most deletions interrupted viral surface epitopes, and are possibly involved in evading immuno-surveillance. Among various clinical factors examined, logistic regression showed that antiviral medication affected the accumulation of deletion mutants (OR = 6.81, 95% CI = 1.296 ~ 35.817, P = 0.023). In chronic carriers of the virus, and individuals with chronic hepatitis, the deletion rate was significantly higher in the antiviral treatment group (Fisher exact test, P = 0.007). Particularly, preS2 deletions were associated with the usage of nucleos(t)ide analog therapy (Fisher exact test, P = 0.023). Dynamic increases in preS1 or preS2 deletions were also observed in quasispecies from samples taken from patients before and after three months of ADV therapy. In vitro experiments demonstrated that preS2 deletions alone

  12. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis


    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  13. High beta experiments in CHS

    International Nuclear Information System (INIS)

    Okamura, S.; Matsuoka, K.; Nishimura, K.


    High beta experiments were performed in the low-aspect-ratio helical device CHS with the volume-averaged equilibrium beta up to 2.1 %. These values (highest for helical systems) are obtained for high density plasmas in low magnetic field heated with two tangential neutral beams. Confinement improvement given by means of turning off gas puffing helped significantly to make high betas. Magnetic fluctuations increased with increasing beta, but finally stopped to increase in the beta range > 1 %. The coherent modes appearing in the magnetic hill region showed strong dependence on the beta values. The dynamic poloidal field control was applied to suppress the outward plasma movement with the plasma pressure. Such an operation gave fixed boundary operations of high beta plasmas in helical systems. (author)

  14. Beta rays and neutrinos

    International Nuclear Information System (INIS)

    Adams, S.F.


    It was over 30 years between the first observation of the enigmatic process of beta decay and the first postulation of the neutrino. It took a further 26 years until the first neutrino was detected and yet another 27 until the electroweak theory was confirmed by the discovery of W and Z particles. This article traces some of the puzzles and paradoxes associated with the history of the neutrino. (author)

  15. Coroutine Sequencing in BETA

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger

    In object-oriented programming, a program execution is viewed as a physical model of some real or imaginary part of the world. A language supporting object-oriented programming must therefore contain comprehensive facilities for modeling phenomena and concepts form the application domain. Many...... applications in the real world consist of objects carrying out sequential processes. Coroutines may be used for modeling objects that alternate between a number of sequential processes. The authors describe coroutines in BETA...

  16. COM Support in BETA

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann


    Component technologies based on binary units of independent production are some of the most important contributions to software architecture and reuse during recent years. Especially the COM technologies and the CORBA standard from the Object Management Group have contributed new and interesting...... principles for software architecture, and proven to be useful in parctice. In this paper ongoing work with component support in the BETA language is described....

  17. Deletion of ultraconserved elements yields viable mice

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Zhu, Yiwen; Visel, Axel; Holt, Amy; Afzal, Veena; Pennacchio, Len A.; Rubin, Edward M.


    Ultraconserved elements have been suggested to retainextended perfect sequence identity between the human, mouse, and ratgenomes due to essential functional properties. To investigate thenecessities of these elements in vivo, we removed four non-codingultraconserved elements (ranging in length from 222 to 731 base pairs)from the mouse genome. To maximize the likelihood of observing aphenotype, we chose to delete elements that function as enhancers in amouse transgenic assay and that are near genes that exhibit markedphenotypes both when completely inactivated in the mouse as well as whentheir expression is altered due to other genomic modifications.Remarkably, all four resulting lines of mice lacking these ultraconservedelements were viable and fertile, and failed to reveal any criticalabnormalities when assayed for a variety of phenotypes including growth,longevity, pathology and metabolism. In addition more targeted screens,informed by the abnormalities observed in mice where genes in proximityto the investigated elements had been altered, also failed to revealnotable abnormalities. These results, while not inclusive of all thepossible phenotypic impact of the deleted sequences, indicate thatextreme sequence constraint does not necessarily reflect crucialfunctions required for viability.

  18. Method for introducing unidirectional nested deletions (United States)

    Dunn, J.J.; Quesada, M.A.; Randesi, M.


    Disclosed is a method for the introduction of unidirectional deletions in a cloned DNA segment. More specifically, the method comprises providing a recombinant DNA construct comprising a DNA segment of interest inserted in a cloning vector. The cloning vector has an f1 endonuclease recognition sequence adjacent to the insertion site of the DNA segment of interest. The recombinant DNA construct is then contacted with the protein pII encoded by gene II of phage f1 thereby generating a single-stranded nick. The nicked DNA is then contacted with E. coli Exonuclease III thereby expanding the single-stranded nick into a single-stranded gap. The single-stranded gapped DNA is then contacted with a single-strand-specific endonuclease thereby producing a linearized DNA molecule containing a double-stranded deletion corresponding in size to the single-stranded gap. The DNA treated in this manner is then incubated with DNA ligase under conditions appropriate for ligation. Also disclosed is a method for producing single-stranded DNA probes. In this embodiment, single-stranded gapped DNA, produced as described above, is contacted with a DNA polymerase in the presence of labeled nucleotides to fill in the gap. This DNA is then linearized by digestion with a restriction enzyme which cuts outside the DNA segment of interest. The product of this digestion is then denatured to produce a labeled single-stranded nucleic acid probe. 1 fig.

  19. Rare human diseases: 9p deletion syndrome

    Directory of Open Access Journals (Sweden)

    Galagan V.O.


    Full Text Available Objective of the study was to review the anamnesis, pheno - and genotype in patients with rare chromosome disorders such as 9p deletion syndrome. Genetic methods of investigation (clinical and genealogical, cytogenetic, FISH- method, paraclinical and instrumental methods of examination were used. Karyotyping was performed by the G-method of differential staining of chromosomes. Only three cases of pathology were diagnosed in the Medical Genetics Center over the last 10 years. By anamnesis data nobody in the probands’ families had bad habits, was exposed to occupational hazards, took part in the elimination of the Chernobyl accident or lived in contaminated areas. Clinical signs of diseases have not been identified in probands’ parents. All probands had trigonocephaly, bilateral epicanthal folds, ocular hypertelorism, downslanting palpebral fissures, long philtrum, flat face and nasal bridge, low set ears with malformed auricles. Two patients of three ones had exophthalmos, contracture of the second and third fingers, abnormal external genitalia. In all three cases there was monosomy of chromosome 9 of critical segment p 24. Normal karyotypes were seen in all parents, so there were three cases of new mutations of 9p deletion syndrome. Retardation of physical, psycho-spech, mental development in proband with or without congenital anomalies requires medical genetic counseling in a specialized institution. Cases of reproductive loss in anamnesis require cytogenetic investigation of fetal membranes and amniotic fluid.

  20. Coexistence of Extended Spectrum Beta-Lactamases, AmpC Beta-Lactamases and Metallo-Beta-Lactamases in Acinetobacter baumannii from burns patients: a report from a tertiary care centre of India


    Gupta, V.; Garg, R.; Garg, S.; Chander, J.; Attri, A.K.


    Multidrug-resistant Acinetobacter baumanii is a major pathogen encountered in pyogenic infections, especially from burns patients in hospital settings. Often there is also coexistence of multiple beta-lactamase enzymes responsible for beta-lactam resistance in a single isolate, which further complicates treatment options. We conducted a study on burn wound pus samples obtained from the burns unit of our hospital. Phenotypic tests were used to determine the Extended Spectrum Beta-Lactamase, Am...

  1. Discoidin domain receptor 1 is activated independently of beta(1) integrin

    DEFF Research Database (Denmark)

    Vogel, W; Brakebusch, C; Fässler, R


    independent of the epidermal growth factor (EGF) receptor. In cells that endogenously express both DDR1 and the EGF receptor, stimulation with EGF does not induce DDR activation. Third, we detected full DDR1 activation after collagen stimulation in cells that have been treated with blocking antibodies...... for alpha(2)beta(1) integrin or in cells with a targeted deletion of the beta(1) integrin gene. Finally, we show that overexpression of dominant negative DDR1 in the myoblast cell line C2C12 blocks cellular differentiation and the formation of myofibers....

  2. Preventive Effects of Beta-Hydroxy-Beta-Methyl Butyrate

    Directory of Open Access Journals (Sweden)

    N. Ravanbakhsh


    Full Text Available Aims: One of the major factors in sudden cardiac arrest is the initiation and continuation of deadly arrhythmias during ischemia. It is known that beta-hydroxy-beta-methylbutyrate (HMB has useful effects such as anti-inflammatory and anti-apoptosis effects in the skeletal muscles. The aim of this study was to investigate the preventive effects of HMB on the ventricular arrhythmias due to the ischemia. Materials & Methods: In the experimental study, 30 Wistar male rats were randomly divided into three groups including control, HMB320, and HMB700. As control group received normal saline, HMB320 and HMB700 groups orally received 320 and 700 mg/Kg HMB as gavage for 2 weeks, respectively. The rats, having been anesthetized, underwent 30-minute ischemia. Then, the numbers of premature ventricular contractions (PVC, the appearance duration of ventricular tachycardia (VT, and the ventricular fibrillation (VF were assessed. Data was analyzed by SPSS 16 software using Kruskal-Walis, one-way ANOVA, Tukey’s post-hoc, and Chi-square tests. Findings: There was a significant reduction in the mean PVC number in HMB320 and HMB700 groups than control group (p=0.001. In addition, there was such a significant difference between the groups received the doses (p=0.008. There was a reduction in the mean appearance duration of VT in HMB320 and HMB700 groups than control group (p=0.001. There was a significant reduction in the mean appearance duration of VF in HMB700 group compared to control group, only (p=0.003. Conclusion: Through arrhythmias reduction, 2-week preventive consumption of HMB might considerably reduce the severe side effects of ischemia.

  3. Are there ethnic differences in deletions in the dystrophin gene?

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, M.; Verma, I.C. [All India Inst. of Medical Sciences, New Delhi (India)


    We studied 160 cases of Duchenne muscular dystrophy (DMD) drawn from all parts of India, using multiplex PCR of 27 exons. Of these, 103 (64.4%) showed intragenic deletions. Most (69.7%) of the deletions involved exons 45-51. The phenotype of cases with deletion of single exons did not differ significantly from those with deletion of multiple exons. The distribution of deletions in studies from different countries was variable, but this was accounted for either by the small number of cases studied, or by fewer exons analyzed. It is concluded that there is likely to be no ethnic difference with respect to deletions in the DMD gene. 38 refs., 2 figs., 3 tabs.

  4. LHCb: $2\\beta_s$ measurement at LHCb

    CERN Multimedia

    Conti, G


    A measurement of $2\\beta_s$, the phase of the $B_s-\\bar{B_s}$ oscillation amplitude with respect to that of the ${\\rm b} \\rightarrow {\\rm c^{+}}{\\rm W^{-}}$ tree decay amplitude, is one of the key goals of the LHCb experiment with first data. In the Standard Model (SM), $2\\beta_s$ is predicted to be $0.0360^{+0.0020}_{-0.0016} \\rm rad$. The current constraints from the Tevatron are: $2\\beta_{s}\\in[0.32 ; 2.82]$ at 68$\\%$CL from the CDF experiment and $2\\beta_{s}=0.57^{+0.24}_{-0.30}$ from the D$\\oslash$ experiment. Although the statistical uncertainties are large, these results hint at the possible contribution of New Physics in the $B_s-\\bar{B_s}$ box diagram. After one year of data taking at LHCb at an average luminosity of $\\mathcal{L}\\sim2\\cdot10^{32}\\rm cm^{-2} \\rm s^{-1}$ (integrated luminosity $\\mathcal{L}_{\\rm int}\\sim 2 \\rm fb^{-1}$), the expected statistical uncertainty on the measurement is $\\sigma(2\\beta_s)\\simeq 0.03$. This uncertainty is similar to the $2\\beta_s$ value predicted by the SM.

  5. Transgenic overexpression of active calcineurin in beta-cells results in decreased beta-cell mass and hyperglycemia.

    Directory of Open Access Journals (Sweden)

    Ernesto Bernal-Mizrachi


    Full Text Available Glucose modulates beta-cell mass and function through an initial depolarization and Ca(2+ influx, which then triggers a number of growth regulating signaling pathways. One of the most important downstream effectors in Ca(2+ signaling is the calcium/Calmodulin activated serine threonine phosphatase, calcineurin. Recent evidence suggests that calcineurin/NFAT is essential for beta-cell proliferation, and that in its absence loss of beta-cells results in diabetes. We hypothesized that in contrast, activation of calcineurin might result in expansion of beta-cell mass and resistance to diabetes.To determine the role of activation of calcineurin signaling in the regulation of pancreatic beta-cell mass and proliferation, we created mice that expressed a constitutively active form of calcineurin under the insulin gene promoter (caCn(RIP. To our surprise, these mice exhibited glucose intolerance. In vitro studies demonstrated that while the second phase of Insulin secretion is enhanced, the overall insulin secretory response was conserved. Islet morphometric studies demonstrated decreased beta-cell mass suggesting that this was a major component responsible for altered Insulin secretion and glucose intolerance in caCn(RIP mice. The reduced beta-cell mass was accompanied by decreased proliferation and enhanced apoptosis.Our studies identify calcineurin as an important factor in controlling glucose homeostasis and indicate that chronic depolarization leading to increased calcineurin activity may contribute, along with other genetic and environmental factors, to beta-cell dysfunction and diabetes.

  6. Structural domains required for channel function of the mouse transient receptor potential protein homologue TRP1beta. (United States)

    Engelke, Michael; Friedrich, Olaf; Budde, Petra; Schäfer, Christina; Niemann, Ursula; Zitt, Christof; Jüngling, Eberhard; Rocks, Oliver; Lückhoff, Andreas; Frey, Jürgen


    Transient receptor potential proteins (TRP) are supposed to participate in the formation of store-operated Ca(2+) influx channels by co-assembly. However, little is known which domains facilitate the interaction of subunits. Contribution of the N-terminal coiled-coil domain and ankyrin-like repeats and the putative pore region of the mouse TRP1beta (mTRP1beta) variant to the formation of functional cation channels were analyzed following overexpression in HEK293 (human embryonic kidney) cells. MTRP1beta expressing cells exhibited enhanced Ca(2+) influx and enhanced whole-cell membrane currents compared to mTRP1beta deletion mutants. Using a yeast two-hybrid assay only the coiled-coil domain facilitated homodimerization of the N-terminus. These results suggest that the N-terminus of mTRP1beta is required for structural organization thus forming functional channels.

  7. Beta-blocker use and clinical outcomes after primary vascular surgery

    DEFF Research Database (Denmark)

    Høgh, A.; Lindholt, J.S.; Nielsen, Henrik


    To explore the associations between beta-blocker use and clinical outcomes (death, hospitalisation with myocardial infarction (MI) or stroke, major amputation and recurrent vascular surgery) after primary vascular reconstruction.......To explore the associations between beta-blocker use and clinical outcomes (death, hospitalisation with myocardial infarction (MI) or stroke, major amputation and recurrent vascular surgery) after primary vascular reconstruction....

  8. A Comprehensive tRNA Deletion Library Unravels the Genetic Architecture of the tRNA Pool (United States)

    Bloom-Ackermann, Zohar; Navon, Sivan; Gingold, Hila; Towers, Ruth; Pilpel, Yitzhak; Dahan, Orna


    Deciphering the architecture of the tRNA pool is a prime challenge in translation research, as tRNAs govern the efficiency and accuracy of the process. Towards this challenge, we created a systematic tRNA deletion library in Saccharomyces cerevisiae, aimed at dissecting the specific contribution of each tRNA gene to the tRNA pool and to the cell's fitness. By harnessing this resource, we observed that the majority of tRNA deletions show no appreciable phenotype in rich medium, yet under more challenging conditions, additional phenotypes were observed. Robustness to tRNA gene deletion was often facilitated through extensive backup compensation within and between tRNA families. Interestingly, we found that within tRNA families, genes carrying identical anti-codons can contribute differently to the cellular fitness, suggesting the importance of the genomic surrounding to tRNA expression. Characterization of the transcriptome response to deletions of tRNA genes exposed two disparate patterns: in single-copy families, deletions elicited a stress response; in deletions of genes from multi-copy families, expression of the translation machinery increased. Our results uncover the complex architecture of the tRNA pool and pave the way towards complete understanding of their role in cell physiology. PMID:24453985

  9. Panchromatic cooperative hyperspectral adaptive wide band deletion repair method (United States)

    Jiang, Bitao; Shi, Chunyu


    In the hyperspectral data, the phenomenon of stripe deletion often occurs, which seriously affects the efficiency and accuracy of data analysis and application. Narrow band deletion can be directly repaired by interpolation, and this method is not ideal for wide band deletion repair. In this paper, an adaptive spectral wide band missing restoration method based on panchromatic information is proposed, and the effectiveness of the algorithm is verified by experiments.

  10. NPL deletion policy for RCRA-regulated TSD facilities finalized

    International Nuclear Information System (INIS)



    Under a new policy published by EPA on March 20, 1995, certain sites may be deleted from the National Priorities List (NPL) and deferred to RCRA corrective action. To be deleted from the NPL, a site must (1) be regulated under RCRA as a treatment, storage, or disposal (TSD) facility and (2) meet the four criteria specified by EPA. The new NPL deletion policy, which does not pertain to federal TSD facilities, became effective on April 19, 1995. 1 tab

  11. Clival encephalocele and 5q15 deletion: a case report. (United States)

    Puvabanditsin, Surasak; Malik, Imran; Garrow, Eugene; Francois, Lissa; Mehta, Rajeev


    A preterm neonate presenting with respiratory distress after birth was found to have a clival encephalocele, which is a variant of a basal encephalocele, and hypoplasia of the cerebellum. Genetic studies revealed a small deletion of the long arm of chromosome 5: 5q15 deletion. We report a rare variant of a basal encephalocele with a cerebellar malformation and 5q15 deletion. © The Author(s) 2014.

  12. Male gametophytic sterility. 1 - Gametic sterilities and deletions in petunia

    Energy Technology Data Exchange (ETDEWEB)

    Cornu, A.; Maizonnier, D. (Station d' Amelioration des Plantes de l' I.N.R.A., Dijon (France))


    Terminal deletions induced by ionizing radiations in Petunia are not sexually transmitted. Cytogenetic study of plants with a heterozygous deletion and their progenies shows that this lack of transmission is accompanied by a gametic semi-sterility due to the fact that gametes carrying the deleted chromosome are not viable. The interest of such a male sterility with a gametophytic determinism for the study of sporophyte-gametophyte relationships is underlined.

  13. HOXA genes cluster: clinical implications of the smallest deletion


    Pezzani, Lidia; Milani, Donatella; Manzoni, Francesca; Baccarin, Marco; Silipigni, Rosamaria; Guerneri, Silvana; Esposito, Susanna


    Background HOXA genes cluster plays a fundamental role in embryologic development. Deletion of the entire cluster is known to cause a clinically recognizable syndrome with mild developmental delay, characteristic facies, small feet with unusually short and big halluces, abnormal thumbs, and urogenital malformations. The clinical manifestations may vary with different ranges of deletions of HOXA cluster and flanking regions. Case presentation We report a girl with the smallest deletion reporte...

  14. The influence of large deletions on the mutation frequency induced by tritiated water and X-radiation in male Drosophila melanogaster post-meiotic germ cells

    International Nuclear Information System (INIS)

    Fossett, N.G.; Byrne, B.J.; Kelley, S.J.; Tucker, A.B.; Arbour-Reily, P.; Lee, W.R.


    Tritium beta radiation ( 3 H β-radiation) in the form of tritiated water was used to induce mutations at the alcohol dehydrogenase (Adh) locus in male Drosophila melanogaster post-meiotic germ cells. All 23 Adh null mutations were large deletions (>20 kb), determined by genetic complementation and Southern blot analyses. 27 Adh null mutations have been induced by 100-kVp X-rays and have been genetically and molecularly characterized. In contrast to 3 H β-radiation, 100-kVp X-rays induced a bimodal distribution of Adh null mutations, intragenic mutations, ≤250 bp, and large deletions, >100 kb. A statistically significant difference was observed between the frequency of large deletions (23/23 or 1.0) induced by 3 H β-radiation and the frequency of large deletions (19/27 or 0.7) induced by 100-kVp X-rays. However, a statistical difference was not observed between the size distribution of the large deletions induced by 3 H β-radiation and X-rays. The relative deletion frequency (RDF) induced by 3 H β-radiation and 100-kVp X-rays was (1.0/0.7=1.4). The relative biological effectiveness (RBE) of these two radiation sources was 1.4, determined from the ratio of the regression coefficients of the respective 3 H β-radiation and X-ray sex-linked recessive lethal (SLRL) dose-response data. The large difference in size between the two classes of X-ray-induced Adh null mutations and the increase in mutation frequency and deletion frequency for 3 H β-radiation with respect to X-rays may indicate that the relative deletion frequency (RDF) is the molecular biological basis for the increase in the RBE for radiation sources with a mean LET value ≤10 keV/μm

  15. Interactions between an alpha-helix and a beta-sheet. Energetics of alpha/beta packing in proteins. (United States)

    Chou, K C; Némethy, G; Rumsey, S; Tuttle, R W; Scheraga, H A


    Conformational energy computations have been carried out to determine the favorable ways of packing a right-handed alpha-helix on a right-twisted antiparallel or parallel beta-sheet. Co-ordinate transformations have been developed to relate the position and orientation of the alpha-helix to the beta-sheet. The packing was investigated for a CH3CO-(L-Ala)16-NHCH3 alpha-helix interacting with five-stranded beta-sheets composed of CH3CO-(L-Val)6-NHCH3 chains. All internal and external variables for both the alpha-helix and the beta-sheet were allowed to change during energy minimization. Four distinct classes of low-energy packing arrangements were found for the alpha-helix interacting with both the parallel and the anti-parallel beta-sheet. The classes differ in the orientation of the axis of the alpha-helix relative to the direction of the strands of the right-twisted beta-sheet. In the class with the most favorable arrangement, the alpha-helix is oriented along the strands of the beta-sheet, as a result of attractive non-bonded side-chain-side-chain interactions along the entire length of the alpha-helix. A class with nearly perpendicular orientation of the helix axis to the strands is also of low energy, because it allows similarly extensive attractive interactions. In the other two classes, the helix is oriented diagonally relative to the strands of the beta-sheet. In one of them, it interacts with the convex surface near the middle of the saddle-shaped twisted beta-sheet. In the other, it is oriented along the concave diagonal of the beta-sheet and, therefore, it interacts only with the corner regions of the sheet, so that this packing is energetically less favorable. The packing arrangements involving an antiparallel and a parallel beta-sheet are generally similar, although the antiparallel beta-sheet has been found to be more flexible. The major features of 163 observed alpha/beta packing arrangements in 37 proteins are accounted for in terms of the computed

  16. A Comparative Study of Quantum and Classical Deletion

    International Nuclear Information System (INIS)

    Shen Yao; Hao Liang; Long Guilu


    Here in this letter, we study the difference between quantum and classical deletion. We point out that the linear mapping deletion operation used in the impossibility proof for quantum systems applies also to classical system. The general classical deletion operation is a combined operation of measurement and transformation, i.e., first read the state and then transfer the state to the standard blank state. Though both quantum information and classical information can be deleted in an open system, quantum information cannot be recovered while classical information can be recovered. (general)

  17. Comprehensive analysis of pathogenic deletion variants in Fanconi anemia genes. (United States)

    Flynn, Elizabeth K; Kamat, Aparna; Lach, Francis P; Donovan, Frank X; Kimble, Danielle C; Narisu, Narisu; Sanborn, Erica; Boulad, Farid; Davies, Stella M; Gillio, Alfred P; Harris, Richard E; MacMillan, Margaret L; Wagner, John E; Smogorzewska, Agata; Auerbach, Arleen D; Ostrander, Elaine A; Chandrasekharappa, Settara C


    Fanconi anemia (FA) is a rare recessive disease resulting from mutations in one of at least 16 different genes. Mutation types and phenotypic manifestations of FA are highly heterogeneous and influence the clinical management of the disease. We analyzed 202 FA families for large deletions, using high-resolution comparative genome hybridization arrays, single-nucleotide polymorphism arrays, and DNA sequencing. We found pathogenic deletions in 88 FANCA, seven FANCC, two FANCD2, and one FANCB families. We find 35% of FA families carry large deletions, accounting for 18% of all FA pathogenic variants. Cloning and sequencing across the deletion breakpoints revealed that 52 FANCA deletion ends, and one FANCC deletion end extended beyond the gene boundaries, potentially affecting neighboring genes with phenotypic consequences. Seventy-five percent of the FANCA deletions are Alu-Alu mediated, predominantly by AluY elements, and appear to be caused by nonallelic homologous recombination. Individual Alu hotspots were identified. Defining the haplotypes of four FANCA deletions shared by multiple families revealed that three share a common ancestry. Knowing the exact molecular changes that lead to the disease may be critical for a better understanding of the FA phenotype, and to gain insight into the mechanisms driving these pathogenic deletion variants. © 2014 WILEY PERIODICALS, INC.

  18. 75 FR 1355 - Procurement List Additions and Deletions (United States)


    .../Location: Janitorial Services, Jamestown Service Center, 8430 Country Club Street, Jamestown, ND. NPA..., the following products and services are deleted from the Procurement List: Products Business Cards NSN...

  19. Base substitutions, frameshifts, and small deletions constitute ionizing radiation-induced point mutations in mammalian cells

    International Nuclear Information System (INIS)

    Grosovsky, A.J.; de Boer, J.G.; de Jong, P.J.; Drobetsky, E.A.; Glickman, B.W.


    The relative role of point mutations and large genomic rearrangements in ionizing radiation-induced mutagenesis has been an issue of long-standing interest. Recent studies using Southern blotting analysis permit the partitioning of ionizing radiation-induced mutagenesis in mammalian cells into detectable deletions and major genomic rearrangements and into point mutations. The molecular nature of these point mutations has been left unresolved; they may include base substitutions as well as small deletions, insertions, and frame-shifts below the level of resolution of Southern blotting analysis. In this investigation, we have characterized a collection of ionizing radiation-induced point mutations at the endogenous adenine phosphoribosyltransferase (aprt) locus of Chinese hamster ovary cells at the DNA sequence level. Base substitutions represented approximately equal to 2/3 of the point mutations analyzed. Although the collection of mutants is relatively small, every possible type of base substitution event has been recovered. These mutations are well distributed throughout the coding sequence with only one multiple occurrence. Small deletions represented the remainder of characterized mutants; no insertions have been observed. Sequence-directed mechanisms mediated by direct repeats could account for some of the observed deletions, while others appear to be directly attributable to radiation-induced strand breakage

  20. Alu-mediated large deletion of the CDSN gene as a cause of peeling skin disease. (United States)

    Wada, T; Matsuda, Y; Muraoka, M; Toma, T; Takehara, K; Fujimoto, M; Yachie, A


    Peeling skin disease (PSD) is an autosomal recessive skin disorder caused by mutations in CDSN and is characterized by superficial peeling of the upper epidermis. Corneodesmosin (CDSN) is a major component of corneodesmosomes that plays an important role in maintaining epidermis integrity. Herein, we report a patient with PSD caused by a novel homozygous large deletion in the 6p21.3 region encompassing the CDSN gene, which abrogates CDSN expression. Several genes including C6orf15, PSORS1C1, PSORS1C2, CCHCR1, and TCF19 were also deleted, however, the patient showed only clinical features typical of PSD. The deletion size was 59.1 kb. Analysis of the sequence surrounding the breakpoint showed that both telomeric and centromeric breakpoints existed within Alu-S sequences that were oriented in opposite directions. These results suggest an Alu-mediated recombination event as the mechanism underlying the deletion in our patient. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Rhes deletion is neuroprotective in the 3-nitropropionic acid model of Huntington's disease


    Mealer, Robert G.; Subramaniam, Srinivasa; Snyder, Solomon H.


    Although the mutated protein causing Huntington's disease (HD) is expressed throughout the body, the major pathology of HD is localized to the striatum of the brain. We previously reported that the striatal-enriched protein Rhes binds the mutated huntingtin protein and enhances its cytotoxicity. We now demonstrate that Rhes-deleted mice are dramatically protected from neurotoxicity and motor dysfunction in a striatal-specific model of HD elicited by 3-nitropropionic acid. This finding suggest...

  2. Enantioselective synthesis of alpha,beta-disubstituted-beta-amino acids. (United States)

    Sibi, Mukund P; Prabagaran, Narayanasamy; Ghorpade, Sandeep G; Jasperse, Craig P


    Highly diastereoselective and enantioselective addition of N-benzylhydroxylamine to imides 17 and 20-30 produces alpha,beta-trans-disubstituted N-benzylisoxazolidinones 19 and 31-41. These reactions proceed in 60-96% ee with 93-99% de's using 5 mol % of Mg(NTf2)2 and ligand 18. The product isoxazolidinones can be hydrogenolyzed directly to provide alpha,beta-disubstituted-beta-amino acids.

  3. Klf5 deletion promotes Pten deletion-initiated luminal-type mouse prostate tumors through multiple oncogenic signaling pathways. (United States)

    Xing, Changsheng; Ci, Xinpei; Sun, Xiaodong; Fu, Xiaoying; Zhang, Zhiqian; Dong, Eric N; Hao, Zhao-Zhe; Dong, Jin-Tang


    Krüppel-like factor 5 (KLF5) regulates multiple biologic processes. Its function in tumorigenesis appears contradictory though, showing both tumor suppressor and tumor promoting activities. In this study, we examined whether and how Klf5 functions in prostatic tumorigenesis using mice with prostate-specific deletion of Klf5 and phosphatase and tensin homolog (Pten), both of which are frequently inactivated in human prostate cancer. Histologic analysis demonstrated that when one Pten allele was deleted, which causes mouse prostatic intraepithelial neoplasia (mPIN), Klf5 deletion accelerated the emergence and progression of mPIN. When both Pten alleles were deleted, which causes prostate cancer, Klf5 deletion promoted tumor growth, increased cell proliferation, and caused more severe morphologic and molecular alterations. Homozygous deletion of Klf5 was more effective than hemizygous deletion. Unexpectedly, while Pten deletion alone expanded basal cell population in a tumor as reported, Klf5 deletion in the Pten-null background clearly reduced basal cell population while expanding luminal cell population. Global gene expression profiling, pathway analysis, and experimental validation indicate that multiple mechanisms could mediate the tumor-promoting effect of Klf5 deletion, including the up-regulation of epidermal growth factor and its downstream signaling molecules AKT and ERK and the inactivation of the p15 cell cycle inhibitor. KLF5 also appears to cooperate with several transcription factors, including CREB1, Sp1, Myc, ER and AR, to regulate gene expression. These findings validate the tumor suppressor function of KLF5. They also yield a mouse model that shares two common genetic alterations with human prostate cancer-mutation/deletion of Pten and deletion of Klf5.

  4. Coexistence of Southeast Asian ovalocytosis and beta-thalassemia: a molecular and hematological analysis. (United States)

    Fucharoen, Goonnapa; Fucharoen, Supan; Singsanan, Sanita; Sanchaisuriya, Kanokwan


    We describe hematological and molecular characterization of a Thai female who had Southeast Asian ovalocytosis (SAO) associated with beta+-thalassemia trait. The proband had mild microcytosis with Hb 12.9 g/dl, Hct 35.8%, MCV 74.4 fl, MCH 26.8 pg, MCHC 36.0 g/dl, and elevated Hb A2 (5.6%), characteristics of beta-thalassemia trait. Peripheral blood film examination revealed prominent ovalocytosis. However, a one-tube osmotic fragility (OF) test commonly used for thalassemia screening was negative and a normal OF curve was observed. Further polymerase chain reaction (PCR) analyses identified the beta(-28A-G) mutation in the beta-globin gene and a 27 bp deletion in erythrocyte band 3 protein gene, indicating a genetically compound heterozygote. Hematological data of the proband was comparatively presented with those of eight female and 15 male carriers of pure beta-thalassemia with the same mutation. The finding demonstrates that although the association of the SAO and beta-thalassemia does not produce a more severe clinical picture, this could lead to a mis-screening of beta-thalassemia using an OF test as a primary screening test. Additional blood film examination followed by PCR could help in the detection of this unusual genetic interaction in the region. (c) 2006 Wiley-Liss, Inc.

  5. beta1 integrins are not required for the maintenance of lymphocytes within intestinal epithelia

    DEFF Research Database (Denmark)

    Marsal, Jan; Brakebusch, Cord; Bungartz, Gerd


    beta(1) integrins are thought to play a central role in maintaining lymphocytes within mucosal epithelia via their interactions with extracellular matrix proteins and subepithelial cellular components within and underlying the basement membrane. In the current study type a (CD8alphabetaTCRalphabe......beta(1) integrins are thought to play a central role in maintaining lymphocytes within mucosal epithelia via their interactions with extracellular matrix proteins and subepithelial cellular components within and underlying the basement membrane. In the current study type a (CD8alphabeta......TCRalphabeta) and type b (CD8alphaalphaTCRgammadelta and CD8alphaalphaTCRalphabeta) intraepithelial lymphocyte (IEL) subsets within the mouse small intestine were found to express functional beta(1) integrin and the beta(1) integrin alpha chain partners alpha(1), alpha(2), and alpha(4). Using inducible beta(1) integrin......-knockout bone marrow-chimeric mice we demonstrate that IEL expression of alpha(1) and alpha(2) but not alpha(4) is dependent on expression of the beta(1) chain. Importantly, deletion of the beta(1) chain in IEL did not alter the number or composition of lymphocytes within the intestinal epithelium. Thus, while...

  6. Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus

    International Nuclear Information System (INIS)

    Papadopoulo, D.; Guillouf, C.; Moustacchi, E.; Mohrenweiser, H.


    Fanconi anemia (FA) is an inherited human disorder associated with a predisposition to cancer and characterized by anomalies in the processing of DNA cross-links and certain monoadducts. The authors reported previously that the frequency of psoralen-photoinduced mutations at the HPRT locus is lower in FA cells than in normal cells. This hypomutability is shown here to be associated with an increased frequency of deletions in the HPRT gene when either a mixture of cross-links and monoadducts or monoadducts alone are induced. Molecular analysis of mutants in the HPRT gene was carried out. In normal cells the majority of spontaneous and induced mutants are point mutations whereas in FA deletion mutations predominate. In that case a majority of mutants were found to lack individual exons or small clusters of exons whereas in normal cells large (complete or major gene loss) and small deletions are almost equally represented. Thus they propose that the FA defect lies in a mutagenic pathway that, in normal cells, involves by passing lesions and subsequent gap filling by a recombinational process during replication

  7. Beta measurement evaluation and upgrade

    International Nuclear Information System (INIS)

    Swinth, K.L.; Rathbun, L.A.; Roberson, P.L.; Endres, G.W.R.


    This program focuses on the resolution of problems associated with the field measurement of the beta dose component at Department of Energy (DOE) facilities. The change in DOE programs, including increased efforts in improved waste management and decontamination and decommissioning (D and D) of facilities, coupled with beta measurement problems identified at Three Mile Island has increased the need to improve beta measurements. In FY 1982, work was initiated to provide a continuing effort to identify problems associated with beta dose assessment at DOE facilities. The problems identified resulted in the development of this program. The investigation includes (1) an assessment of measurement systems now in use, (2) development of improved calibration systems and procedures, (3) application of innovative beta dosimetry concepts, (4) investigation of new instruments or concepts for monitoring and spectroscopy, and (5) development of recommendations to assure an adequate beta measurement program within DOE facilities

  8. The Golgi localization of phosphatidylinositol transfer protein beta requires the protein kinase C-dependent phosphorylation of serine 262 and is essential for maintaining plasma membrane sphingomyelin levels. (United States)

    van Tiel, Claudia M; Westerman, Jan; Paasman, Marten A; Hoebens, Martha M; Wirtz, Karel W A; Snoek, Gerry T


    Recombinant mouse phosphatidylinositol transfer protein (PI-TP)beta is a substrate for protein kinase C (PKC)-dependent phosphorylation in vitro. Based on site-directed mutagenesis and two-dimensional tryptic peptide mapping, Ser(262) was identified as the major site of phosphorylation and Ser(165) as a minor phosphorylation site. The phospholipid transfer activities of wild-type PI-TP beta and PI-TP beta(S262A) were identical, whereas PI-TP beta(S165A) was completely inactive. PKC-dependent phosphorylation of Ser(262) also had no effect on the transfer activity of PI-TP beta. To investigate the role of Ser(262) in the functioning of PI-TP beta, wtPI-TP beta and PI-TP beta(S262A) were overexpressed in NIH3T3 fibroblast cells. Two-dimensional PAGE analysis of cell lysates was used to separate PI-TP beta from its phosphorylated form. After Western blotting, wtPI-TP beta was found to be 85% phosphorylated, whereas PI-TP beta(S262A) was not phosphorylated. In the presence of the PKC inhibitor GF 109203X, the phosphorylated form of wtPI-TP beta was strongly reduced. Immunolocalization showed that wtPI-TP beta was predominantly associated with the Golgi membranes. In the presence of the PKC inhibitor, wtPI-TP beta was distributed throughout the cell similar to what was observed for PI-TP beta(S262A). In contrast to wtPI-TP beta overexpressors, cells overexpressing PI-TP beta(S262A) were unable to rapidly replenish sphingomyelin in the plasma membrane upon degradation by sphingomyelinase. This implies that PKC-dependent association with the Golgi complex is a prerequisite for PI-TP beta to express its effect on sphingomyelin metabolism.

  9. Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Pyo; Kim, Baek Gil [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Gao, Ming-Qing; Kang, Suki [Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Nam Hoon, E-mail: [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)


    Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  10. [Clinical management of beta-thalassaemia]. (United States)

    Thuret, Isabelle


    Beta-thalassemia syndromes are autosomal recessive disorders related to the inability to produce beta-globin chains. Thalassemia major is by definition a transfusion dependent anemia and iron overload is the leading cause of death and morbidity. Beta-thalassemia is rarely encountered in France where patients mainly originated from Mediterranean countries and South East Asia. Recently, two major advances have substantially improved the disease management: oral iron chelation therapy and the introduction of cardiac MRI for monitoring cardiac iron. Hematopoietic stem cell transplantation remains, in clinical practice, the only curative approach and is proposed to children having an HLA-identical sibling. Diagnosis of thalassemia trait is important in order to propose genetic counseling to couples at risk. Thalassemia intermedia is a clinical entity where anemia is mild or moderate, requiring no or occasional transfusion. Clinical severity increases with age with a more severe anemia, thrombotic complications and extra-medullary hematopoiesis. Iron overload, optimally monitored with liver MRI, occurs in adult patients and is related to increased iron hyper-absorption.

  11. Conditional Betas and Investor Uncertainty


    Fernando D. Chague


    We derive theoretical expressions for market betas from a rational expectation equilibrium model where the representative investor does not observe if the economy is in a recession or an expansion. Market betas in this economy are time-varying and related to investor uncertainty about the state of the economy. The dynamics of betas will also vary across assets according to the assets' cash-flow structure. In a calibration exercise, we show that value and growth firms have cash-flow structures...

  12. Dynamic returns of beta arbitrage


    Nascimento, Mafalda


    This thesis studies the patterns of the abnormal returns of the beta strategy. The topic can be helpful for professional investors, who intend to achieve a better performance in their portfolios. Following the methodology of Lou, Polk, & Huang (2016), the COBAR measure is computed in order to determine the levels of beta arbitrage in the market in each point in time. It is argued that beta arbitrage activity can have impact on the returns of the beta strategy. In fact, it is demonstrated that...

  13. Integration of BETA with Eclipse

    DEFF Research Database (Denmark)

    Andersen, Peter; Madsen, Ole Lehrmann; Enevoldsen, Mads Brøgger


    This paper presents language interoperability issues appearing in order to implement support for the BETA language in the Java-based Eclipse integrated development environment. One of the challenges is to implement plug-ins in BETA and be able to load them in Eclipse. In order to do this, some fo...... it is possible to implement plug-ins in BETA and even inherit from Java classes. In the paper the two approaches are described together with part of the mapping from BETA to Java class files.

  14. Simultaneous beta and gamma spectroscopy (United States)

    Farsoni, Abdollah T.; Hamby, David M.


    A phoswich radiation detector for simultaneous spectroscopy of beta rays and gamma rays includes three scintillators with different decay time characteristics. Two of the three scintillators are used for beta detection and the third scintillator is used for gamma detection. A pulse induced by an interaction of radiation with the detector is digitally analyzed to classify the type of event as beta, gamma, or unknown. A pulse is classified as a beta event if the pulse originated from just the first scintillator alone or from just the first and the second scintillator. A pulse from just the third scintillator is recorded as gamma event. Other pulses are rejected as unknown events.

  15. Brand deletion: How the decision-making approach affects deletion success

    Directory of Open Access Journals (Sweden)

    Víctor Temprano-García


    Full Text Available Literature on brand deletion (BD, a critical and topical decision within a firm's marketing strategy, is extremely scarce. The present research is concerned with the decision-making process and examines the effect on BD success of three different approaches to decision-making – rational, intuitive and political – and of the interaction between the rational and political approaches. The moderating effect of the type of BD – i.e., total brand killing or disposal vs. brand name change – is also analyzed. The model is tested on a sample of 155 cases of BD. Results point to positive effects on BD success of both rationality and intuition, and a negative effect of politics. Findings also indicate that the negative impact of political behavior on BD success is minimized in the absence of evidence and objective information and when the BD is undertaken through a brand name change. JEL classification: L10, M31, Keywords: Brand deletion, Rational decision-making, Intuitive decision-making, Political decision-making, Brand deletion success

  16. Phosphatase and tensin homologue deleted on chromosome 10 ...

    African Journals Online (AJOL)

    Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor gene deleted or mutated in many human cancers such as glioblastoma, spinal tumors, prostate, bladder, adrenals, thyroid, breast, endometrium, and colon cancers. They result from loss of heterozygosity (LOH) for the PTEN ...

  17. Generalised deletion designs | Gachii | African Journal of Science ...

    African Journals Online (AJOL)

    In this paper asymmetrical single replicate factorial designs are constructed from symmetrical single replicate factorial designs using the deletion technique. The study is along the lines of Voss(1986), Chauhan(1989) and Gachii and Odhiambo(1997). We give results for the general order deletion designs of the form sn-m1(s ...

  18. 24 CFR 990.155 - Addition and deletion of units. (United States)


    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Addition and deletion of units. 990.155 Section 990.155 Housing and Urban Development Regulations Relating to Housing and Urban...; Computation of Eligible Unit Months § 990.155 Addition and deletion of units. (a) Changes in public housing...

  19. 4977-bp mitochondrial DNA deletion in infertile patients with varicocele. (United States)

    Gashti, N G; Salehi, Z; Madani, A H; Dalivandan, S T


    Varicocele is the abnormal inflexion and distension of veins of the pampiniform plexus within spermatic cord and is one of the amendable causes of male infertility. It can increase reactive oxygen species (ROS) production in semen and cause oxidative stress. The purpose of this study was to analyse spermatozoa mtDNA 4977-bp deletion in infertile men with varicocele. To detect 4977-bp deletion in spermatozoa mtDNA, semen samples of 60 infertile patients with clinical varicocele and 90 normal men from northern Iran were prepared. After extraction of spermatozoa total DNA, Gap polymerase chain reaction (Gap PCR) was performed. 4977-bp deletion was observed in 81.66% of patients with varicocele, while approximately 15.55% of controls had this deletion. As spermatozoa from patients with varicocele had a high frequency of occurrence of 4977-bp deletion in mtDNA [OR = 24.18, 95% confidence interval (CI) = 10.15-57.57, P deletion in spermatozoa and cause infertility in north Iranian men. However, to determine the relation between sperm mtDNA 4977-bp deletion and varicocele-induced infertility, larger population-based studies are needed. It is concluded that there is an association between sperm mtDNA 4977-bp deletion and varicocele-induced infertility in the population studied. © 2013 Blackwell Verlag GmbH.

  20. 34 CFR 5.16 - Deletion of identifying details. (United States)


    ... 34 Education 1 2010-07-01 2010-07-01 false Deletion of identifying details. 5.16 Section 5.16 Education Office of the Secretary, Department of Education AVAILABILITY OF INFORMATION TO THE PUBLIC PURSUANT TO PUB. L. 90-23 (Eff. until 7-14-10) What Records Are Available § 5.16 Deletion of identifying...

  1. 42 CFR 401.118 - Deletion of identifying details. (United States)


    ... 42 Public Health 2 2010-10-01 2010-10-01 false Deletion of identifying details. 401.118 Section 401.118 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Deletion of identifying details. When CMS publishes or otherwise makes available an opinion or order...

  2. Coexistence of 9p Deletion Syndrome and Autism Spectrum Disorder (United States)

    Günes, Serkan; Ekinci, Özalp; Ekinci, Nuran; Toros, Fevziye


    Deletion or duplication of the short arm of chromosome 9 may lead to a variety of clinical conditions including craniofacial and limb abnormalities, skeletal malformations, mental retardation, and autism spectrum disorder. Here, we present a case report of 5-year-old boy with 9p deletion syndrome and autism spectrum disorder.

  3. Linguistic and Psychomotor Development in Children with Chromosome 14 Deletions (United States)

    Zampini, Laura; D'Odorico, Laura; Zanchi, Paola; Zollino, Marcella; Neri, Giovanni


    The present study focussed on a specific type of rare genetic condition: chromosome 14 deletions. Children with this genetic condition often show developmental delays and brain and neurological problems, although the type and severity of symptoms varies depending on the size and location of the deleted genetic material. The specific aim of the…

  4. 76 FR 78248 - Procurement List; Addition and Deletions (United States)


    .... Service Type/Location: Laundry Service, Stratton Medical Center, 113 Holland Ave, Albany, NY. [[Page 78249...: Addition to and Deletions from the Procurement List. SUMMARY: This action adds a service to the Procurement... disabilities, and deletes products and services from the Procurement List previously furnished by such agencies...

  5. 75 FR 49481 - Procurement List; Additions and Deletion (United States)


    ... added to the Procurement List: Services Service Type/Locations: Laundry Service, Atlanta VA Medical...: Additions to and deletion from the Procurement List. SUMMARY: This action adds services to the Procurement... disabilities and deletes a service from the Procurement List previously furnished by such agency. DATES...

  6. 78 FR 21916 - Procurement List; Addition And Deletions (United States)


    ..., the following service is added to the Procurement List: Service Service Type/Location: Laundry Service...: Addition to and Deletions from the Procurement List. SUMMARY: This action adds a service to the Procurement... disabilities, and deletes products and services from the Procurement List previously furnished by such agencies...

  7. 78 FR 53733 - Procurement List Additions and Deletions (United States)


    .../Location: Industrial Laundry Service, Bureau of Engraving and Printing, 9000 Blue Mound Road, Fort Worth...: Additions to and Deletions from the Procurement List. SUMMARY: This action adds products and services to the... severe disabilities, and deletes services from the Procurement List previously provided by such agencies...

  8. Recurrence and Variability of Germline EPCAM Deletions in Lynch Syndrome

    NARCIS (Netherlands)

    Kuiper, Roland P.; Vissers, Lisenka E. L. M.; Venkatachalam, Ramprasath; Bodmer, Danielle; Hoenselaar, Eveline; Goossens, Monique; Haufe, Aline; Kamping, Eveline; Niessen, Renee C.; Hogervorst, Frans B. L.; Gille, Johan J. P.; Redeker, Bert; Tops, Carli M. J.; van Gijn, Marielle E.; van den Ouweland, Ans M. W.; Rahner, Nils; Steinke, Verena; Kahl, Philip; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Stemmler, Susanne; Betz, Beate; Hutter, Pierre; Bunyan, David J.; Syngal, Sapna; Culver, Julie O.; Graham, Tracy; Chan, Tsun L.; Nagtegaal, Iris D.; van Krieken, J. Han J. M.; Schackert, Hans K.; Hoogerbrugge, Nicoline; van Kessel, Ad Geurts; Ligtenberg, Marjolijn J. L.

    Recently, we identified 3' end deletions in the EPCAM gene as a novel cause of Lynch syndrome. These truncating EPCAM deletions cause allele-specific epigenetic silencing of the neighboring DNA mismatch repair gene MSH2 in tissues expressing EPCAM. Here we screened a cohort of unexplained Lynch-like

  9. A major genetic component of BSE susceptibility (United States)

    Juling, Katrin; Schwarzenbacher, Hermann; Williams, John L; Fries, Ruedi


    Background Coding variants of the prion protein gene (PRNP) have been shown to be major determinants for the susceptibility to transmitted prion diseases in humans, mice and sheep. However, to date, the effects of polymorphisms in the coding and regulatory regions of bovine PRNP on bovine spongiform encephalopathy (BSE) susceptibility have been considered marginal or non-existent. Here we analysed two insertion/deletion (indel) polymorphisms in the regulatory region of bovine PRNP in BSE affected animals and controls of four independent cattle populations from UK and Germany. Results In the present report, we show that two previously reported 23- and 12-bp insertion/deletion (indel) polymorphisms in the regulatory region of bovine PRNP are strongly associated with BSE incidence in cattle. Genotyping of BSE-affected and control animals of UK Holstein, German Holstein, German Brown and German Fleckvieh breeds revealed a significant overrepresentation of the deletion alleles at both polymorphic sites in diseased animals (P = 2.01 × 10-3 and P = 8.66 × 10-5, respectively). The main effect on susceptibility is associated with the 12-bp indel polymorphism. Compared with non-carriers, heterozygous and homozygous carriers of the 12-bp deletion allele possess relatively higher risks of having BSE, ranging from 1.32 to 4.01 and 1.74 to 3.65 in the different breeds. These values correspond to population attributable risks ranging from 35% to 53%. Conclusion Our results demonstrate a substantial genetic PRNP associated component for BSE susceptibility in cattle. Although the BSE risk conferred by the deletion allele of the 12-bp indel in the regulatory region of PRNP is substantial, the main risk factor for BSE in cattle is environmental, i.e. exposure to feedstuffs contaminated with the infectious agent. PMID:17014722

  10. A major genetic component of BSE susceptibility

    Directory of Open Access Journals (Sweden)

    Williams John L


    Full Text Available Abstract Background Coding variants of the prion protein gene (PRNP have been shown to be major determinants for the susceptibility to transmitted prion diseases in humans, mice and sheep. However, to date, the effects of polymorphisms in the coding and regulatory regions of bovine PRNP on bovine spongiform encephalopathy (BSE susceptibility have been considered marginal or non-existent. Here we analysed two insertion/deletion (indel polymorphisms in the regulatory region of bovine PRNP in BSE affected animals and controls of four independent cattle populations from UK and Germany. Results In the present report, we show that two previously reported 23- and 12-bp insertion/deletion (indel polymorphisms in the regulatory region of bovine PRNP are strongly associated with BSE incidence in cattle. Genotyping of BSE-affected and control animals of UK Holstein, German Holstein, German Brown and German Fleckvieh breeds revealed a significant overrepresentation of the deletion alleles at both polymorphic sites in diseased animals (P = 2.01 × 10-3 and P = 8.66 × 10-5, respectively. The main effect on susceptibility is associated with the 12-bp indel polymorphism. Compared with non-carriers, heterozygous and homozygous carriers of the 12-bp deletion allele possess relatively higher risks of having BSE, ranging from 1.32 to 4.01 and 1.74 to 3.65 in the different breeds. These values correspond to population attributable risks ranging from 35% to 53%. Conclusion Our results demonstrate a substantial genetic PRNP associated component for BSE susceptibility in cattle. Although the BSE risk conferred by the deletion allele of the 12-bp indel in the regulatory region of PRNP is substantial, the main risk factor for BSE in cattle is environmental, i.e. exposure to feedstuffs contaminated with the infectious agent.

  11. Genetic counselling in the beta-thalassaemias

    Directory of Open Access Journals (Sweden)

    Adonis S. Ioannides


    Full Text Available The beta-thalassaemias are very important genetic disorders of haemoglobin synthesis and are amongst the commonest monogenic disorders. In view of the severity of beta-thalassaemia major, a number of screening programmes have been developed aimed at reducing the number of individuals born with the condition. Genetic counsellingplays a vital role in this process supporting the successful implementation of screening and delineating available options to at risk individuals. This review assesses the contribution of genetic counsellingat each stage of this process in the context of new diagnostic techniques and therapeutic options and discusses some of the more challenging aspects such as genotype/ phenotype correlation and coinheritance of other genetic conditions or genetic modifiers.

  12. Attenuation of monkeypox virus by deletion of genomic regions (United States)

    Lopera, Juan G.; Falendysz, Elizabeth A.; Rocke, Tonie E.; Osorio, Jorge E.


    Monkeypox virus (MPXV) is an emerging pathogen from Africa that causes disease similar to smallpox. Two clades with different geographic distributions and virulence have been described. Here, we utilized bioinformatic tools to identify genomic regions in MPXV containing multiple virulence genes and explored their roles in pathogenicity; two selected regions were then deleted singularly or in combination. In vitro and in vivostudies indicated that these regions play a significant role in MPXV replication, tissue spread, and mortality in mice. Interestingly, while deletion of either region led to decreased virulence in mice, one region had no effect on in vitro replication. Deletion of both regions simultaneously also reduced cell culture replication and significantly increased the attenuation in vivo over either single deletion. Attenuated MPXV with genomic deletions present a safe and efficacious tool in the study of MPX pathogenesis and in the identification of genetic factors associated with virulence.

  13. Role of DNA deletion length in mutation and cell survival

    International Nuclear Information System (INIS)

    Braby, L.A.; Morgan, T.L.


    A model is presented which is based on the assumption that malignant transformation, mutation, chromosome aberration, and reproductive death of cells are all manifestations of radiation induced deletions in the DNA of the cell, and that the size of the deletion in relation to the spacing of essential genes determines the consequences of that deletion. It is assumed that two independent types of potentially lethal lesions can result in DNA deletions, and that the relative numbers of these types of damage is dependent on radiation quality. The repair of the damage reduces the length of a deletion, but does not always eliminate it. The predictions of this model are in good agreement with a wide variety of experimental evidence. (author)

  14. Identification of active anti-inflammatory principles of beta- beta ...

    African Journals Online (AJOL)

    chromatography. Components of the extracts were identified by thin layer chromatography (TLC) scanner and UV-visible spectroscopy, using scopoletin as standard. Results: ... basic coumarin skeleton ring structure reduce ... Figure 2: Thin-layer chromatogram: (1) Ethanol extract; (2) Dichloromethane fraction; (3) Beta-beta.

  15. Improved limits on beta(-) and beta(-) decays of Ca-48

    Czech Academy of Sciences Publication Activity Database

    Bakalyarov, A.; Balysh, A.; Barabash, AS.; Beneš, P.; Briancon, C.; Brudanin, V. B.; Čermák, P.; Egorov, V.; Hubert, F.; Hubert, P.; Korolev, NA.; Kosjakov, VN.; Kovalík, Alojz; Lebedev, NA.; Novgorodov, A. F.; Rukhadze, NI.; Štekl, NI.; Timkin, VV.; Veleshko, IE.; Vylov, T.; Umatov, VI.


    Roč. 76, č. 9 (2002), s. 545-547 ISSN 0021-3640 Institutional research plan: CEZ:AV0Z1048901 Keywords : beta decay * double beta decay * Ca-48 Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 1.483, year: 2002

  16. Conversion of beta-methylbutyric acid to beta-hydroxy-beta-methylbutyric acid by Galactomyces reessii.


    Lee, I Y; Nissen, S L; Rosazza, J P


    beta-Hydroxy-beta-methylbutyric acid (HMB) has been shown to increase strength and lean mass gains in humans undergoing resistance-exercise training. HMB is currently marketed as a calcium salt of HMB, and thus, environmentally sound and inexpensive methods of manufacture are being sought. This study investigates the microbial conversion of beta-methylbutyric acid (MBA) to HMB by cultures of Galactomyces reessii. Optimal concentrations of MBA were in the range of 5 to 20 g/liter for HMB produ...

  17. Homozygous PMS2 deletion causes a severe colorectal cancer and multiple adenoma phenotype without extraintestinal cancer. (United States)

    Will, Olivia; Carvajal-Carmona, Luis G; Gorman, Patricia; Howarth, Kimberley M; Jones, Angela M; Polanco-Echeverry, Guadalupe M; Chinaleong, Jo-Anne; Günther, Thomas; Silver, Andrew; Clark, Susan K; Tomlinson, Ian


    We report a patient of Indian descent with parental consanguinity, who developed 10 carcinomas and 35 adenomatous polyps at age 23 and duodenal adenocarcinoma at age 25. He also had dysmorphic features, mental retardation, and café-au-lait spots but no brain tumor. We aimed to establish his molecular diagnosis. Germ-line screening for APC and MYH/MUTYH mutations was normal as was immunohistochemistry for MLH1 and MSH2 proteins. Investigation by array-comparative genomic hybridization revealed deletion of a small region on chromosome 7. Using polymerase chain reaction, this region was refined to a 400-kilobase deletion, which included exons 9-15 of the PMS2 gene, and all coding regions of oncomodulin, TRIAD3, and FSCN1. The deletion was confirmed as homozygous, and both parents were carriers. Immunohistochemistry showed absent PMS2 expression in all tumors and normal tissue. Most tumors showed microsatellite instability, more marked at dinucleotide than mononucleotide repeats. The tumors harbored no somatic mutations in APC, BRAF, AXIN2, or beta-catenin, but KRAS2 and TGFBR2 mutations were found. Our patient represents a novel phenotype for homozygous PMS2 mutation and perhaps the most severe colorectal cancer phenotype-in terms of numbers of malignancies at an early age-described to date. PMS2 mutations-and perhaps other homozygous mismatch repair mutations-should be considered in any patient presenting with multiple gastrointestinal tumors, since our patient could not be distinguished clinically from cases with attenuated familial adenomatous polyposis or MUTYH-associated polyposis.

  18. Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels: implication in the pathogenesis of Alzheimer's disease. (United States)

    Aliev, Gjumrakch; Gasimov, Eldar; Obrenovich, Mark E; Fischbach, Kathryn; Shenk, Justin C; Smith, Mark A; Perry, George


    The pathogenesis that is primarily responsible for Alzheimer's disease (AD) and cerebrovascular accidents (CVA) appears to involve chronic hypoperfusion. We studied the ultrastructural features of vascular lesions and mitochondria in brain vascular wall cells from human AD biopsy samples and two transgenic mouse models of AD, yeast artificial chromosome (YAC) and C57B6/SJL Tg (+), which overexpress human amyloid beta precursor protein (AbetaPP). In situ hybridization using probes for normal and 5 kb deleted human and mouse mitochondrial DNA (mtDNA) was performed along with immunocytochemistry using antibodies against the Abeta peptide processed from AbetaPP, 8-hydroxy-2'-guanosine (8OHG), and cytochrome c oxidase (COX). More amyloid deposition, oxidative stress markers as well as mitochondrial DNA deletions and structural abnormalities were present in the vascular walls of the human AD samples and the AbetaPP-YAC and C57B6/SJL Tg (+) transgenic mice compared to age-matched controls. Ultrastructural damage in perivascular cells highly correlated with endothelial lesions in all samples. Therefore, pharmacological interventions, directed at correcting the chronic hypoperfusion state, may change the natural course of the development of dementing neurodegeneration.

  19. Ku80-deleted cells are defective at base excision repair

    International Nuclear Information System (INIS)

    Li, Han; Marple, Teresa; Hasty, Paul


    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H 2 O 2 and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs

  20. Ku80-deleted cells are defective at base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Li, Han [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain); Marple, Teresa [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Hasty, Paul, E-mail: [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain)


    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H{sub 2}O{sub 2} and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs.

  1. Pathological mechanisms underlying single large‐scale mitochondrial DNA deletions (United States)

    Rocha, Mariana C.; Rosa, Hannah S.; Grady, John P.; Blakely, Emma L.; He, Langping; Romain, Nadine; Haller, Ronald G.; Newman, Jane; McFarland, Robert; Ng, Yi Shiau; Gorman, Grainne S.; Schaefer, Andrew M.; Tuppen, Helen A.; Taylor, Robert W.


    Objective Single, large‐scale deletions in mitochondrial DNA (mtDNA) are a common cause of mitochondrial disease. This study aimed to investigate the relationship between the genetic defect and molecular phenotype to improve understanding of pathogenic mechanisms associated with single, large‐scale mtDNA deletions in skeletal muscle. Methods We investigated 23 muscle biopsies taken from adult patients (6 males/17 females with a mean age of 43 years) with characterized single, large‐scale mtDNA deletions. Mitochondrial respiratory chain deficiency in skeletal muscle biopsies was quantified by immunoreactivity levels for complex I and complex IV proteins. Single muscle fibers with varying degrees of deficiency were selected from 6 patient biopsies for determination of mtDNA deletion level and copy number by quantitative polymerase chain reaction. Results We have defined 3 “classes” of single, large‐scale deletion with distinct patterns of mitochondrial deficiency, determined by the size and location of the deletion. Single fiber analyses showed that fibers with greater respiratory chain deficiency harbored higher levels of mtDNA deletion with an increase in total mtDNA copy number. For the first time, we have demonstrated that threshold levels for complex I and complex IV deficiency differ based on deletion class. Interpretation Combining genetic and immunofluorescent assays, we conclude that thresholds for complex I and complex IV deficiency are modulated by the deletion of complex‐specific protein‐encoding genes. Furthermore, removal of mt‐tRNA genes impacts specific complexes only at high deletion levels, when complex‐specific protein‐encoding genes remain. These novel findings provide valuable insight into the pathogenic mechanisms associated with these mutations. Ann Neurol 2018;83:115–130 PMID:29283441

  2. Hydroxyurea responses in clinically varied beta, HbE-beta thalassaemia and sickle cell anaemia patients of Eastern India. (United States)

    Chatterjee, Tridip; Chakravarty, Amit; Chakravarty, Sudipa


    The haematological and clinical response to hydroxyurea was estimated in HbE-beta, beta thalassaemia and sickle cell anaemia patients of Eastern India, with variable clinical severity and transfusion requirement to determine whether hydroxyurea can help these patients to maintain their steady haemoglobin level without blood transfusions. Three hundred patients (189 HbE-beta thalassaemia, 95 beta thalassaemia and 16 other haemoglobinopathies including sickle cell anaemia) were selected for hydroxyurea therapy and were followed up for 48-60 months. Results suggest significant response to hydroxyurea therapy in 19 beta and 99 HbE-beta patients in the transfusion-dependent group (GR-I). All of them became transfusion-independent while on hydroxyurea therapy. The majority of responding patients were IVS1-5(G-C) in one of their alleles in HbE-beta cases (83 out of 119). Though IVS1-5(G-C) was found to be the commonest mutation in our selected patients, the mutational background of the patients does not found to have any significant correlation with the response category towards hydroxyurea as per the results observed in our study. But, the drug works pretty well in most of the transfusion-dependent patients, as these patients were withdrawn from regular blood transfusion. At the same time, partial or no response to the drug hydroxyurea was also recorded in our study.

  3. Thymosin beta 4 and thymosin beta 10 expression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    W. Theunissen


    Full Text Available Thymosin beta 4 (Tβ4 and thymosin beta 10 (Tβ10 are two members of the beta-thymosin family involved in many cellular processes such as cellular motility, angiogenesis, inflammation, cell survival and wound healing. Recently, a role for beta-thymosins has been proposed in the process of carcinogenesis as both peptides were detected in several types of cancer. The aim of the present study was to investigate the expression pattern of Tβ4 and Tβ10 in hepatocellular carcinoma (HCC. To this end, the expression pattern of both peptides was analyzed in liver samples obtained from 23 subjects diagnosed with HCC. Routinely formalin-fixed and paraffin-embedded liver samples were immunostained by indirect immunohistochemistry with polyclonal antibodies to Tβ4 and Tβ10. Immunoreactivity for Tβ4 and Tβ10 was detected in the liver parenchyma of the surrounding tumor area. Both peptides showed an increase in granular reactivity from the periportal to the periterminal hepatocytes. Regarding HCC, Tβ4 reactivity was detected in 7/23 cases (30% and Tβ10 reactivity in 22/23 (97% cases analyzed, adding HCC to human cancers that express these beta-thymosins. Intriguing finding was seen looking at the reactivity of both peptides in tumor cells infiltrating the surrounding liver. Where Tβ10 showed a strong homogeneous expression, was Tβ4 completely absent in cells undergoing stromal invasion. The current study shows expression of both beta-thymosins in HCC with marked differences in their degree of expression and frequency of immunoreactivity. The higher incidence of Tβ10 expression and its higher reactivity in tumor cells involved in stromal invasion indicate a possible major role for Tβ10 in HCC progression.

  4. Association of. beta. -glucosidase with intact cells of thermoactinomyces

    Energy Technology Data Exchange (ETDEWEB)

    Haegerdal, B; Harris, H; Pye, E K


    The location of the ..beta..-glucosidase activity in a whole culture broth of the thermophilic organism Thermoactinomyces has been studied. Little ..beta..-glucosidase activity was found in the culture filtrate, while the culture solids contained the major part of the activity of the whole culture broth. The activity does not appear to be adsorbed to the culture solids; rather there is evidence that it is an intracellular soluble enzyme(s). The pH and temperature optima for a crude ..beta..-glucosidase preparation were determined to be pH 6.5 and 50 to 55/sup 0/C. Enzyme activity studies indicate that the same enzyme(s) accounts for the ..beta..-glucosidase and the cellobiase activities. The validity of using the filter paper activity of culture filtrates from Thermoactinomyces to predict the total saccharification of cellulosic materials to glucose is discussed.

  5. Stabilization of beta-catenin induces pancreas tumor formation. (United States)

    Heiser, Patrick W; Cano, David A; Landsman, Limor; Kim, Grace E; Kench, James G; Klimstra, David S; Taketo, Maketo M; Biankin, Andrew V; Hebrok, Matthias


    beta-Catenin signaling within the canonical Wnt pathway is essential for pancreas development. However, the pathway is normally down-regulated in the adult organ. Increased cytoplasmic and nuclear localization of beta-catenin can be detected in nearly all human solid pseudopapillary neoplasms (SPN), a rare tumor with low malignant potential. Conversely, pancreatic ductal adenocarcinoma (PDA) accounts for the majority of pancreatic tumors and is among the leading causes of cancer death. Whereas activating mutations within beta-catenin and other members of the canonical Wnt pathway are rare, recent reports have implicated Wnt signaling in the development and progression of human PDA. Here, we sought to address the role of beta-catenin signaling in pancreas tumorigenesis. Using Cre/lox technology, we conditionally activated beta-catenin in a subset of murine pancreatic cells in vivo. Activation of beta-catenin results in the formation of large pancreatic tumors at a high frequency in adult mice. These tumors resemble human SPN based on morphologic and immunohistochemical comparisons. Interestingly, stabilization of beta-catenin blocks the formation of pancreatic intraepithelial neoplasia (PanIN) in the presence of an activating mutation in Kras that is known to predispose individuals to PDA. Instead, mice in which beta-catenin and Kras are concurrently activated develop distinct ductal neoplasms that do not resemble PanIN lesions. These results demonstrate that activation of beta-catenin is sufficient to induce pancreas tumorigenesis. Moreover, they indicate that the sequence in which oncogenic mutations are acquired has profound consequences on the phenotype of the resulting tumor.

  6. [Molecular characterization of heterozygous beta-thalassemia in Lanzarote, Spain]. (United States)

    Calvo-Villas, José Manuel; de la Iglesia Iñigo, Silvia; Ropero Gradilla, Paloma; Zapata Ramos, María Francisca; Cuesta Tovar, Jorge; Sicilia Guillén, Francisco


    The aim of this study was to determine the molecular defects of heterozygous beta thalassaemia and to ascertain their distribution in Lanzarote. Molecular characterization was achieved by real time polymerase chain reaction (RT-PCR LightCycler, Roche), PCR-ARMS (PCR-amplification reaction mutations system) and DNA sequencing on an automated DNA sequencer. Two hundred forty-three heterozygous beta thalassaemia carriers were included between July 1991 and February 2007. RT-PCR detected the molecular defect in 81% of the beta thalassaemia chromosomes analyzed [113 codon CD 39 (C --> T); 41 IVS-1-nt-110 (G --> A), 25 IVS 1-nt-1 (G --> A) and 19 IVS 1-nt-6 (T --> C)]. The remaining 12 molecular defects included the deletion 619 bp (7.8%) and the mutations -28 (A --> G), IVS1-nt-2 (T --> G), CD 41/42 (-TTCT), CD 8/9 (+G), CD 51 (-C), CD 22 (G --> T) and CD 24 (T --> A), CD 67 (-TG) and the novel mutation CD 20/21-TGGA. The distribution of the mutations is similar to that found in the Mediterranean area. The increasing migratory flow received in the Canary Islands may explain the emergence of new mutations not reported before in our area.

  7. Detection of genomic deletions in rice using oligonucleotide microarrays

    Directory of Open Access Journals (Sweden)

    Bordeos Alicia


    Full Text Available Abstract Background The induction of genomic deletions by physical- or chemical- agents is an easy and inexpensive means to generate a genome-saturating collection of mutations. Different mutagens can be selected to ensure a mutant collection with a range of deletion sizes. This would allow identification of mutations in single genes or, alternatively, a deleted group of genes that might collectively govern a trait (e.g., quantitative trait loci, QTL. However, deletion mutants have not been widely used in functional genomics, because the mutated genes are not tagged and therefore, difficult to identify. Here, we present a microarray-based approach to identify deleted genomic regions in rice mutants selected from a large collection generated by gamma ray or fast neutron treatment. Our study focuses not only on the utility of this method for forward genetics, but also its potential as a reverse genetics tool through accumulation of hybridization data for a collection of deletion mutants harboring multiple genetic lesions. Results We demonstrate that hybridization of labeled genomic DNA directly onto the Affymetrix Rice GeneChip® allows rapid localization of deleted regions in rice mutants. Deletions ranged in size from one gene model to ~500 kb and were predicted on all 12 rice chromosomes. The utility of the technique as a tool in forward genetics was demonstrated in combination with an allelic series of mutants to rapidly narrow the genomic region, and eventually identify a candidate gene responsible for a lesion mimic phenotype. Finally, the positions of mutations in 14 mutants were aligned onto the rice pseudomolecules in a user-friendly genome browser to allow for rapid identification of untagged mutations Conclusion We demonstrate the utility of oligonucleotide arrays to discover deleted genes in rice. The density and distribution of deletions suggests the feasibility of a

  8. The best-beta CAPM

    NARCIS (Netherlands)

    Zou, L.


    The issue of 'best-beta' arises as soon as potential errors in the Sharpe-Lintner-Black capital asset pricing model (CAPM) are acknowledged. By incorporating a target variable into the investor preferences, this study derives a best-beta CAPM (BCAPM) that maintains the CAPM's theoretical appeal and

  9. Beta decay of Cu-56

    NARCIS (Netherlands)

    Borcea, R; Aysto, J; Caurier, E; Dendooven, P; Doring, J; Gierlik, M; Gorska, M; Grawe, H; Hellstrom, M; Janas, Z; Jokinen, A; Karny, M; Kirchner, R; La Commara, M; Langanke, K; Martinez-Pinedo, G; Mayet, P; Nieminen, A; Nowacki, F; Penttila, H; Plochocki, A; Rejmund, M; Roeckl, E; Schlegel, C; Schmidt, K; Schwengner, R; Sawicka, M


    The proton-rich isotope Cu-56 was produced at the GSI On-Line Mass Separator by means of the Si-28(S-32, p3n) fusion-evaporation reaction. Its beta -decay properties were studied by detecting beta -delayed gamma rays and protons. A half-Life of 93 +/- 3 ms was determined for Cu-56. Compared to the

  10. BETA SPECTRA. I. Negatrons spectra

    International Nuclear Information System (INIS)

    Grau Malonda, A.; Garcia-Torano, E.


    Using the Fermi theory of beta decay, the beta spectra for 62 negatrons emitters have been computed introducing a correction factor for unique forbidden transitions. These spectra are plotted vs. energy, once normal i sed, and tabulated with the related Fermi functions. The average and median energies are calculated. (Author)

  11. Review of the beta situation

    International Nuclear Information System (INIS)

    Sheffield, J.


    This note lists some of the possible causes of beta limitation in tokamak and discusses what is known and what is involved in investigating them. The motivation for preparing this note is the observed degradation of confinement with increasing beta poloidal β/sub p/ and beam power P/sub b/ in ISX-B

  12. RAVEN Beta Release

    International Nuclear Information System (INIS)

    Rabiti, Cristian; Alfonsi, Andrea; Cogliati, Joshua Joseph; Mandelli, Diego; Kinoshita, Robert Arthur; Wang, Congjian; Maljovec, Daniel Patrick; Talbot, Paul William


    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  13. RAVEN Beta Release

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Congjian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Maljovec, Daniel Patrick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Talbot, Paul William [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  14. Tau deletion promotes brain insulin resistance. (United States)

    Marciniak, Elodie; Leboucher, Antoine; Caron, Emilie; Ahmed, Tariq; Tailleux, Anne; Dumont, Julie; Issad, Tarik; Gerhardt, Ellen; Pagesy, Patrick; Vileno, Margaux; Bournonville, Clément; Hamdane, Malika; Bantubungi, Kadiombo; Lancel, Steve; Demeyer, Dominique; Eddarkaoui, Sabiha; Vallez, Emmanuelle; Vieau, Didier; Humez, Sandrine; Faivre, Emilie; Grenier-Boley, Benjamin; Outeiro, Tiago F; Staels, Bart; Amouyel, Philippe; Balschun, Detlef; Buee, Luc; Blum, David


    The molecular pathways underlying tau pathology-induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration. However, tau pathology may also result in the loss of specific physiological tau functions, which are largely unknown but could contribute to neuronal dysfunction. In the present study, we uncovered a novel function of tau in its ability to regulate brain insulin signaling. We found that tau deletion leads to an impaired hippocampal response to insulin, caused by altered IRS-1 and PTEN (phosphatase and tensin homologue on chromosome 10) activities. Our data also demonstrate that tau knockout mice exhibit an impaired hypothalamic anorexigenic effect of insulin that is associated with energy metabolism alterations. Consistently, we found that tau haplotypes are associated with glycemic traits in humans. The present data have far-reaching clinical implications and raise the hypothesis that pathophysiological tau loss-of-function favors brain insulin resistance, which is instrumental for cognitive and metabolic impairments in Alzheimer's disease patients. © 2017 Marciniak et al.

  15. Interactions between two beta-sheets. Energetics of beta/beta packing in proteins. (United States)

    Chou, K C; Némethy, G; Rumsey, S; Tuttle, R W; Scheraga, H A


    The analysis of the interactions between regularly folded segments of the polypeptide chain contributes to an understanding of the energetics of protein folding. Conformational energy-minimization calculations have been carried out to determine the favorable ways of packing two right-twisted beta-sheets. The packing of two five-stranded beta-sheets was investigated, with the strands having the composition CH3CO-(L-Ile)6-NHCH3 in one beta-sheet and CH3CO-(L-Val)6-NHCH3 in the other. Two distinct classes of low-energy packing arrangements were found. In the class with lowest energies, the strands of the two beta-sheets are aligned nearly parallel (or antiparallel) with each other, with a preference for a negative orientation angle, because this arrangement corresponds to the best complementary packing of the two twisted saddle-shaped beta-sheets. In the second class, with higher interaction energies, the strands of the two beta-sheets are oriented nearly perpendicular to each other. While the surfaces of the two beta-sheets are not complementary in this arrangement, there is good packing between the corner of one beta-sheet and the interior part of the surface of the other, resulting in a favorable energy of packing. Both classes correspond to frequently observed orientations of beta-sheets in proteins. In proteins, the second class of packing is usually observed when the two beta-sheets are covalently linked, i.e. when a polypeptide strand passes from one beta-sheet to the other, but we have shown here that a large contribution to the stabilization of this packing arrangement arises from noncovalent interactions.

  16. PAX3 gene deletion detected by microarray analysis in a girl with hearing loss. (United States)

    Drozniewska, Malgorzata; Haus, Olga


    Deletions of the PAX3 gene have been rarely reported in the literature. Mutations of this gene are a common cause of Waardenburg syndrome type 1 and 3. We report a 16 year old female presenting hearing loss and normal intellectual development, without major features of Waardenburg syndrome type 1, and without family history of the syndrome. Her phenotype, however, overlaps with features of craniofacial-deafness-hand syndrome. Microarray analysis showed ~862 kb de novo deletion at 2q36.1 including PAX3. The above findings suggest that the rearrangement found in our patient appeared de novo and with high probability is a cause of her phenotype.

  17. Smad signaling pathway is a pivotal component of tissue inhibitor of metalloproteinases-3 regulation by transforming growth factor beta in human chondrocytes. (United States)

    Qureshi, Hamid Yaqoob; Ricci, Gemma; Zafarullah, Muhammad


    Transforming growth factor beta (TGF-beta1) promotes cartilage matrix synthesis and induces tissue inhibitor of metalloproteinases-3 (TIMP-3), which inhibits matrix metalloproteinases, aggrecanases and TNF-alpha-converting enzyme implicated in articular cartilage degradation and joint inflammation. TGF-beta1 activates Akt, ERK and Smad2 pathways in chondrocytes. Here we investigated previously unexplored roles of specific Smads in TGF-beta1 induction of TIMP-3 gene by pharmacological and genetic knockdown approaches. TGF-beta1-induced Smad2 phosphorylation and TIMP-3 protein expression could be inhibited by the Smad2/3 phosphorylation inhibitors, PD169316 and SB203580 and by Smad2-specific siRNA. Specific inhibitor of Smad3 (SIS3) and Smad3 siRNA abolished TGF-beta induction of TIMP-3. Smad2/3 siRNAs also down regulated TIMP-3 promoter-driven luciferase activities, suggesting transcriptional regulation. SiRNA-driven co-Smad4 knockdown abrogated TIMP-3 augmentation by TGF-beta. TIMP-3 promoter deletion analysis revealed that -828 deletion retains the original promoter activity while -333 and -167 deletions display somewhat reduced activity suggesting that most of the TGF-beta-responsive, cis-acting elements are found in the -333 fragment. Chromatin Immunoprecipitation (ChIP) analysis confirmed binding of Smad2 and Smad4 with the -940 and -333 promoter sequences. These results suggest that receptor-activated Smad2 and Smad3 and co-Smad4 critically mediate TGF-beta-stimulated TIMP-3 expression in human chondrocytes and TIMP-3 gene is a target of Smad signaling pathway.

  18. Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways. (United States)

    Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K


    The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene driven by the vitellogenin A2 ERE were transfected into estrogen-treated MCF-7 cells. RXR beta inhibited ERE-driven reporter activity in a dose-dependent and element-specific fashion. This inhibition occurred in the absence of the RXR ligand 9-cis retinoic acid. The RXR beta-induced inhibition was specific for estrogen receptor (ER)-mediated ERE activation because inhibition was observed in ER-negative MDA-MB-231 cells only following transfection of the estrogen-activated ER. No inhibition of the basal reporter activity was observed. The inhibition was not caused by simple competition of RXR beta with the ER for ERE binding, since deletion mutants retaining DNA binding activity but lacking the N-terminal or C-terminal domain failed to inhibit reporter activity. In addition, cross-linking studies indicated the presence of an auxiliary nuclear factor present in MCF-7 cells that contributed to RXR beta binding of the ERE. Studies using known heterodimerization partners of RXR beta confirmed that RXR beta/triiodothyronine receptor alpha heterodimers avidly bind the ERE but revealed the existence of another triiodothyronine-independent pathway of ERE inhibition. These results indicate that estrogen-responsive genes may be negatively regulated by RXR beta through two distinct pathways.

  19. Structural and sequence features of two residue turns in beta-hairpins. (United States)

    Madan, Bharat; Seo, Sung Yong; Lee, Sun-Gu


    Beta-turns in beta-hairpins have been implicated as important sites in protein folding. In particular, two residue β-turns, the most abundant connecting elements in beta-hairpins, have been a major target for engineering protein stability and folding. In this study, we attempted to investigate and update the structural and sequence properties of two residue turns in beta-hairpins with a large data set. For this, 3977 beta-turns were extracted from 2394 nonhomologous protein chains and analyzed. First, the distribution, dihedral angles and twists of two residue turn types were determined, and compared with previous data. The trend of turn type occurrence and most structural features of the turn types were similar to previous results, but for the first time Type II turns in beta-hairpins were identified. Second, sequence motifs for the turn types were devised based on amino acid positional potentials of two-residue turns, and their distributions were examined. From this study, we could identify code-like sequence motifs for the two residue beta-turn types. Finally, structural and sequence properties of beta-strands in the beta-hairpins were analyzed, which revealed that the beta-strands showed no specific sequence and structural patterns for turn types. The analytical results in this study are expected to be a reference in the engineering or design of beta-hairpin turn structures and sequences. © 2014 Wiley Periodicals, Inc.

  20. Usefulness of MLPA in the detection of SHOX deletions. (United States)

    Funari, Mariana F A; Jorge, Alexander A L; Souza, Silvia C A L; Billerbeck, Ana E C; Arnhold, Ivo J P; Mendonca, Berenice B; Nishi, Mirian Y


    SHOX haploinsufficiency causes a wide spectrum of short stature phenotypes, such as Leri-Weill dyschondrosteosis (LWD) and disproportionate short stature (DSS). SHOX deletions are responsible for approximately two thirds of isolated haploinsufficiency; therefore, it is important to determine the most appropriate methodology for detection of gene deletion. In this study, three methodologies for the detection of SHOX deletions were compared: the fluorescence in situ hybridization (FISH), microsatellite analysis and multiplex ligation-dependent probe amplification (MLPA). Forty-four patients (8 LWD and 36 DSS) were analyzed. The cosmid LLNOYCO3'M'34F5 was used as a probe for the FISH analysis and microsatellite analysis were performed using three intragenic microsatellite markers. MLPA was performed using commercial kits. Twelve patients (8 LWD and 4 DSS) had deletions in SHOX area detected by MLPA and 2 patients generated discordant results with the other methodologies. In the first case, the deletion was not detected by FISH. In the second case, both FISH and microsatellite analyses were unable to identify the intragenic deletion. In conclusion, MLPA was more sensitive, less expensive and less laborious; therefore, it should be used as the initial molecular method for the detection of SHOX gene deletion. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  1. Conversion of Deletions during Recombination in Pneumococcal Transformation (United States)

    Lefevre, J. C.; Mostachfi, P.; Gasc, A. M.; Guillot, E.; Pasta, F.; Sicard, M.


    Genetic analysis of 16 deletions obtained in the amiA locus of pneumococcus is described. When present on donor DNA, all deletions increased drastically the frequency of wild-type recombinants in two-point crosses. This effect was maximal for deletions longer than 200 bases. It was reduced for heterologies shorter than 76 bases and did not exist for very short deletions. In three-point crosses in which the deletion was localized between two point mutations, we demonstrated that this excess of wild-type recombinants was the result of a genetic conversion. This conversion extended over several scores of bases outside the deletion. Conversion takes place during the heteroduplex stage of recombination. Therefore, in pneumococcal transformation, long heterologies participated in this heteroduplex configuration. As this conversion did not require an active DNA polymerase A gene it is proposed that the mechanism of conversion is not a DNA repair synthesis but involves breakage and ligation between DNA molecules. Conversion of deletions did not require the Hex system of correction of mismatched bases. It differs also from localized conversion. It appears that it is a process that evolved to correct errors of replication which lead to long heterologies and which are not eliminated by other systems. PMID:2599365

  2. A strong deletion bias in nonallelic gene conversion.

    Directory of Open Access Journals (Sweden)

    Raquel Assis

    Full Text Available Gene conversion is the unidirectional transfer of genetic information between orthologous (allelic or paralogous (nonallelic genomic segments. Though a number of studies have examined nucleotide replacements, little is known about length difference mutations produced by gene conversion. Here, we investigate insertions and deletions produced by nonallelic gene conversion in 338 Drosophila and 10,149 primate paralogs. Using a direct phylogenetic approach, we identify 179 insertions and 614 deletions in Drosophila paralogs, and 132 insertions and 455 deletions in primate paralogs. Thus, nonallelic gene conversion is strongly deletion-biased in both lineages, with almost 3.5 times as many conversion-induced deletions as insertions. In primates, the deletion bias is considerably stronger for long indels and, in both lineages, the per-site rate of gene conversion is orders of magnitudes higher than that of ordinary mutation. Due to this high rate, deletion-biased nonallelic gene conversion plays a key role in genome size evolution, leading to the cooperative shrinkage and eventual disappearance of selectively neutral paralogs.

  3. Deletion of Pr130 Interrupts Cardiac Development in Zebrafish

    Directory of Open Access Journals (Sweden)

    Jie Yang


    Full Text Available Protein phosphatase 2 regulatory subunit B, alpha (PPP2R3A, a regulatory subunit of protein phosphatase 2A (PP2A, is a major serine/threonine phosphatase that regulates crucial function in development and growth. Previous research has implied that PPP2R3A was involved in heart failure, and PR130, the largest transcription of PPP2R3A, functioning in the calcium release of sarcoplasmic reticulum (SR, plays an important role in the excitation-contraction (EC coupling. To obtain a better understanding of PR130 functions in myocardium and cardiac development, two pr130-deletion zebrafish lines were generated using clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated proteins (Cas system. Pr130-knockout zebrafish exhibited cardiac looping defects and decreased cardiac function (decreased fractional area and fractional shortening. Hematoxylin and eosin (H&E staining demonstrated reduced cardiomyocytes. Subsequent transmission electron microscopy revealed that the bright and dark bands were narrowed and blurred, the Z- and M-lines were fogged, and the gaps between longitudinal myocardial fibers were increased. Additionally, increased apoptosis was observed in cardiomyocyte in pr130-knockout zebrafish compared to wild-type (WT. Taken together, our results suggest that pr130 is required for normal myocardium formation and efficient cardiac contractile function.

  4. The autophosphorylation and p34cdc2 phosphorylation sites of casein kinase-2 beta-subunit are not essential for reconstituting the fully-active heterotetrameric holoenzyme

    DEFF Research Database (Denmark)

    Meggio, F; Boldyreff, B; Issinger, O G


    Two mutants of human casein kinase-2 beta-subunit with short deletions at either their amino (delta 1-4) or carboxy (delta 209-215) terminal side have been created that have lost the capability to undergo autophosphorylation and p34cdc2 mediated phosphorylation, respectively. Both mutants give rise...

  5. Derivatives of the Incomplete Beta Function

    Directory of Open Access Journals (Sweden)

    Robert J. Boik


    Full Text Available The incomplete beta function is defined as where Beta(p, q is the beta function. Dutka (1981 gave a history of the development and numerical evaluation of this function. In this article, an algorithm for computing first and second derivatives of Ix,p,q with respect to p and q is described. The algorithm is useful, for example, when fitting parameters to a censored beta, truncated beta, or a truncated beta-binomial model.

  6. Use of beta-adrenoceptor blocking drugs in hyperthyroidism. (United States)

    Feely, J; Peden, N


    There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol (200mg daily), metoprolol (200mg daily); acebutolol (400mg daily), oxprenolol ( 160mg daily), nadolol ( 80mg daily) and timolol (20mg daily) produce a beneficial clinical response equal to that seen with propranolol ( 160mg daily). Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to

  7. Performance of quantum cloning and deleting machines over coherence (United States)

    Karmakar, Sumana; Sen, Ajoy; Sarkar, Debasis


    Coherence, being at the heart of interference phenomena, is found to be an useful resource in quantum information theory. Here we want to understand quantum coherence under the combination of two fundamentally dual processes, viz., cloning and deleting. We found the role of quantum cloning and deletion machines with the consumption and generation of quantum coherence. We establish cloning as a cohering process and deletion as a decohering process. Fidelity of the process will be shown to have connection with coherence generation and consumption of the processes.

  8. Brand deletion: How the decision-making approach affects deletion success


    Víctor Temprano-García; Ana Isabel Rodríguez-Escudero; Javier Rodríguez-Pinto


    Literature on brand deletion (BD), a critical and topical decision within a firm's marketing strategy, is extremely scarce. The present research is concerned with the decision-making process and examines the effect on BD success of three different approaches to decision-making – rational, intuitive and political – and of the interaction between the rational and political approaches. The moderating effect of the type of BD – i.e., total brand killing or disposal vs. brand name change – is also...

  9. Upregulation of B7 molecules (CD80 and CD86) and exacerbated eosinophilic pulmonary inflammatory response in mice lacking the IFN-beta gene

    DEFF Research Database (Denmark)

    Matheu, Victor; Treschow, Alexandra; Navikas, Vaidrius


    . OBJECTIVE: We sought to define the differential role of endogenous IFN-beta in controlling the development of allergic inflammation. METHODS: We assessed whether deletion of the gene encoding IFN-beta (IFNB) with knockout mice participated in the development of allergic response in ovalbumin (OVA......BACKGROUND: IFN-beta has been shown to be effective as therapy for multiple sclerosis. Some reports attributed its beneficial effects to the capacity to induce a T(H)2 response. However, other studies have suggested that endogenous type I IFN might downregulate the allergic response in mice...

  10. Beta1 integrin is not essential for hematopoiesis but is necessary for the T cell-dependent IgM antibody response

    DEFF Research Database (Denmark)

    Brakebusch, Cord; Fillatreau, Simon; Potocnik, Alexandre J


    Several experimental evidences suggested that beta1 integrin-mediated adhesion of hematopoietic stem cells (HSC) is important for their function in the bone marrow (BM). Using induced deletion of the beta1 integrin gene restricted to the hematopoietic system, we show that beta1 integrin...... is not essential for HSC retention in the BM, hematopoiesis, and trafficking of lymphocytes. However, immunization with a T cell-dependent antigen resulted in virtually no IgM production and an increased secretion of IgG in mutant mice, while the response to a T cell-independent type 2 antigen showed decreases...

  11. Development of beta reference radiations

    International Nuclear Information System (INIS)

    Wan Zhaoyong; Cai Shanyu; Li Yanbo; Yin Wei; Feng Jiamin; Sun Yuhua; Li Yongqiang


    A system of beta reference radiation has been developed, that is composed of 740 MBq 147 Pm beta source, 74 MBq and 740 MBq 90 Sr + 90 Y β sources, compensation filters, a source handling tool, a source jig, spacing bars, a shutter, a control unit and a beta dose meter calibration stand. For 740 MBq 147 Pm and 74 MBq 90 Sr + 90 Y beta reference radiations with compensation filters and 740 MBq 90 Sr + 90 Y beta reference radiation without compensation filter, at 20 cm, 30 cm and 30 cm distance separately; the residual energy of maximum is 0.14 MeV, 1.98 MeV and 2.18 MeV separately; the absorbed dose to tissue D (0.07) is 1.547 mGy/h (1996-05-20), 5.037 mGy/h (1996-05-10) and 93.57 mGy/h (1996-05-15) separately; the total uncertainty is 3.0%, 1.7% and 1.7% separately. For the first and the second beta reference radiation, the dose rate variability in the area of 18 cm diameter in the plane perpendicular to the beta-ray beam axis is within +-6% and +-3% separately. (3 refs., 2 tabs., 8 figs.)

  12. A semiconductor beta ray spectrometer

    International Nuclear Information System (INIS)

    Bom, V.R.


    Measurement of energy spectra of beta particles emitted from nuclei in beta-decay processes provides information concerning the mass difference of these nuclei between initial and final state. Moreover, experimental beta spectra yield information on the feeding of the levels in the daughter nucleus. Such data are valuable in the construction and checking of the level schemes. This thesis describes the design, construction, testing and usage of a detector for the accurate measurement of the mentioned spectra. In ch. 2 the design and construction of the beta spectrometer, which uses a hyper-pure germanium crystal for energy determination, is described. A simple wire chamber is used to discriminate beta particles from gamma radiation. Disadvantages arise from the large amounts of scattered beta particles deforming the continua. A method is described to minimize the scattering. In ch. 3 some theoretical aspects of data analysis are described and the results of Monte-Carlo simulations of the summation of annihilation radiation are compared with experiments. Ch. 4 comprises the results of the measurements of the beta decay energies of 103-108 In. 87 refs.; 34 figs.; 7 tabs

  13. BETA (Bitter Electromagnet Testing Apparatus) (United States)

    Bates, Evan M.; Birmingham, William J.; Rivera, William F.; Romero-Talamas, Carlos A.


    The Bitter Electromagnet Testing Apparatus (BETA) is a 1-Tesla (T) prototype of the 10-T Adjustable Long Pulse High-Field Apparatus (ALPHA). These water-cooled resistive magnets use high DC currents to produce strong uniform magnetic fields. Presented here is the successful completion of the BETA project and experimental results validating analytical magnet designing methods developed at the Dusty Plasma Laboratory (DPL). BETA's final design specifications will be highlighted which include electromagnetic, thermal and stress analyses. The magnet core design will be explained which include: Bitter Arcs, helix starters, and clamping annuli. The final version of the magnet's vessel and cooling system are also presented, as well as the electrical system of BETA, which is composed of a unique solid-state breaker circuit. Experimental results presented will show the operation of BETA at 1 T. The results are compared to both analytical design methods and finite element analysis calculations. We also explore the steady state maximums and theoretical limits of BETA's design. The completion of BETA validates the design and manufacturing techniques that will be used in the succeeding magnet, ALPHA.

  14. 22q11.2 deletion syndrome (United States)

    McDonald-McGinn, Donna M.; Sullivan, Kathleen E.; Marino, Bruno; Philip, Nicole; Swillen, Ann; Vorstman, Jacob A. S.; Zackai, Elaine H.; Emanuel, Beverly S.; Vermeesch, Joris R.; Morrow, Bernice E.; Scambler, Peter J.; Bassett, Anne S.


    22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population. PMID:27189754

  15. Heme oxygenase-1 deletion affects stress erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Yu-An Cao

    Full Text Available Homeostatic erythropoiesis leads to the formation of mature red blood cells under non-stress conditions, and the production of new erythrocytes occurs as the need arises. In response to environmental stimuli, such as bone marrow transplantation, myelosuppression, or anemia, erythroid progenitors proliferate rapidly in a process referred to as stress erythropoiesis. We have previously demonstrated that heme oxygenase-1 (HO-1 deficiency leads to disrupted stress hematopoiesis. Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.We used a transplant model to induce stress conditions. In irradiated recipients that received hmox(+/- or hmox(+/+ bone marrow cells, we evaluated (i the erythrocyte parameters in the peripheral blood; (ii the staining intensity of CD71-, Ter119-, and CD49d-specific surface markers during erythroblast differentiation; (iii the patterns of histological iron staining; and (iv the number of Mac-1(+-cells expressing TNF-α. In the spleens of mice that received hmox(+/- cells, we show (i decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii increases in the insoluble iron levels and decreases in the soluble iron levels; (iii increased numbers of Mac-1(+-cells expressing TNF-α; and (iv decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen. Thus, HO-1 may serve as a therapeutic target for controlling erythropoiesis, and the dysregulation of HO-1 may be a predisposing condition for hematologic diseases.

  16. Experiments on double beta decay

    Energy Technology Data Exchange (ETDEWEB)

    Busto, J [Neuchatel Univ. (Switzerland). Inst. de Physique


    The Double Beta Decay, and especially ({beta}{beta}){sub 0{nu}} mode, is an excellent test of Standard Model as well as of neutrino physics. From experimental point of view, a very large number of different techniques are or have been used increasing the sensitivity of this experiments quite a lot (the factor of 10{sup 4} in the last 20 years). In future, in spite of several difficulties, the sensitivity would be increased further, keeping the interest of this very important process. (author) 4 figs., 5 tabs., 21 refs.

  17. Dosimetry of {beta} extensive sources; Dosimetria de fuentes {beta} extensas

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E.L.; Lallena R, A.M. [Departamento de Fisica Moderna, Universidad de Granada, E-18071 Granada (Spain)


    In this work, we have been studied, making use of the Penelope Monte Carlo simulation code, the dosimetry of {beta} extensive sources in situations of spherical geometry including interfaces. These configurations are of interest in the treatment of the called cranealfaringyomes of some synovia leisure of knee and other problems of interest in medical physics. Therefore, its application can be extended toward problems of another areas with similar geometric situation and beta sources. (Author)

  18. [Focus on beta-blockers for vascular specialists in 2012]. (United States)

    Mairesse, S; Blacher, J; Safar, M-E


    Since they were launched on the market in 1964, cardiovascular indications for beta-blockers have been validated and accepted worldwide. Numerous studies and meta-analysis have confirmed their benefits. They reduce mortality in post infarction and acute coronary syndrome populations and also in people with stable coronary heart disease. Moreover, heart failure with systolic left ventricular dysfunction is a major indication for this therapeutic class, providing a 30% decrease in mortality. In patients with permanent atrial fibrillation, beta-blockers are recommended for rate control. In hypertension patients, first-line drug treatment with beta-blockers is currently discussed. Indeed, several studies have shown that patients randomized in the beta-blocker arms experienced more coronary heart and cerebrovascular diseases than comparators. Their lesser effect on central blood pressure decrease could partially explain those results. Nevertheless, beta-blockers are still considered as first-line drugs for hypertension in the French and European guidelines. Long-term comparative studies focusing on central blood pressure are needed. Concerning the other indications for beta-blockers in vascular diseases, their use perioperatively to reduce surgical cardiovascular risk raised much hope, but the most recent results are disappointed and even suggest possible higher mortality. Finally, except for patients with critical ischemia of the lower limbs, presence of peripheral artery disease should probably be considered as a condition favoring their prescription. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  19. Space environment durability of beta cloth in LDEF thermal blankets (United States)

    Linton, Roger C.; Whitaker, Ann F.; Finckenor, Miria M.


    Beta cloth performance for use on long-term space vehicles such as Space Station Freedom (S.S. Freedom) requires resistance to the degrading effects of the space environment. The major issues are retention of thermal insulating properties through maintaining optical properties, preserving mechanical integrity, and generating minimal particulates for contamination-sensitive spacecraft surfaces and payloads. The longest in-flight test of beta cloth's durability was on the Long Duration Exposure Facility (LDEF), where it was exposed to the space environment for 68 months. The LDEF contained 57 experiments which further defined the space environment and its effects on spacecraft materials. It was deployed into low-Earth orbit (LEO) in Apr. 1984 and retrieved Jan. 1990 by the space shuttle. Among the 10,000 plus material constituents and samples onboard were thermal control blankets of multilayer insulation with a beta cloth outer cover and Velcro attachments. These blankets were exposed to hard vacuum, thermal cycling, charged particles, meteoroid/debris impacts, ultraviolet (UV) radiation, and atomic oxygen (AO). Of these space environmental exposure elements, AO appears to have had the greatest effect on the beta cloth. The beta cloth analyzed in this report came from the MSFC Experiment S1005 (Transverse Flat-Plate Heat Pipe) tray oriented approximately 22 deg from the leading edge vector of the LDEF satellite. The location of the tray on LDEF and the placement of the beta cloth thermal blankets are shown. The specific space environment exposure conditions for this material are listed.

  20. Multigene deletions in lung adenocarcinomas from irradiated and control mice

    International Nuclear Information System (INIS)

    Zhang, Y.; Woloschak, G.E.


    K-ras codon 12 point mutations mRb and p53 gene deletions were examined in tissues from 120 normal lungs and lung adenocarcinomas that were Formalin-treated and paraffin-embedded 25 years ago. The results showed that 12 of 60 (20%) lung adenocarcinomas had mRb deletions. All lung adenocarcinomas that were initially found bearing deleted mRb had p53 deletions (15 of 15; 100%). A significantly higher mutation frequency for K-ras codon 12 point mutations was also found in the lung adenocarcinomas from mice exposed to 24 once-weekly neutron irradiation (10 of 10; 100%) compared with those exposed to 24 or 60 once-weekly γ-ray doses (5 of 10; 50%). The data suggested that p53 and K-ras gene alterations were two contributory factors responsible for the increased incidence of lung adenocarcinoma in B6CF 1 male mice exposed to protracted neutron radiation

  1. Additions and deletions to the known cerambycidae (Coleoptera) of Bolivia (United States)

    An additional 137 species and two tribes are added to the known cerambycid fauna of Bolivia while 12 species are deleted. Comments and statistics regarding the growth of knowledge on the Bolivian Cerambycid fauna and species endemicity are included....

  2. 78 FR 75911 - Procurement List; Proposed Additions and Deletions (United States)


    ... persons who are blind or have other severe disabilities and to delete products and a service previously...: General Services Administration, New York, NY NSN: 8955-01-E61-3689--Coffee, Roasted, Ground, 39 oz. bag...

  3. 76 FR 37069 - Procurement List; Proposed Additions and Deletion (United States)


    ... Certification The following products and service are proposed for addition to Procurement List for production by... following product is proposed for deletion from the Procurement List: Product Detergent, Laundry NSN: 7930...

  4. [Effect of sulfonation of polyethersulfone sheets on the adsorption of beta2-microglobulin]. (United States)

    Cheng, Liping; Sun, Shudong; Yue, Yilun; Huang, Jia; Mao, Huayi; Liang, Bo


    This study was performed to evaluate the adsorption of beta2-microglobulin(beta2 M) by blood dialysis membrane materials which are polyethersulfone (PES), sulfonated polyethersulfones, (PES-SO3Na-I and PES-SO3Na-I ) in vitro incubated in human serum and radiolabeled beta2M (125I-beta2 M) solution respectively. In these experiments, the materials were incubated in 125I-beta2 M solution and human serum at the appointed time ranging from 15 minutes to four hours at 37 degrees C, and then the amounts of 125I-beta2M and serum beta2M adsorbed by materials were measured by radioimmunoassay (RIA). In the 125I-beta2 M system, amounts of 125I-beta2M adsorbed by the materials decreased in sequence of PES-SO3 Na-II > PES-SO3Na-I > PES. In the serum system, amounts of beta2M adsorbed reached maximums at 30 minutes and the final adsorptions decreased in sequence of PES-SO3Na-II > PES-SO3Na-I > PES. Sulfonated PES removes beta2M more than PES does and the adsorption of beta2M increases with the increase in the degree of sulfonation. Its ability to remove significant amount of beta2M may result in less beta2M available for incorporation into amyloid. The use of PES-SO3Na membranes lessens the likelihood of dialysis-related amyloidosis (DRA) development, which remains a major source of morbidity for patients treated with long-term hemodialysis.

  5. The interaction of CK2alpha and CK2beta, the subunits of protein kinase CK2, requires CK2beta in a preformed conformation and is enthalpically driven

    DEFF Research Database (Denmark)

    Raaf, Jennifer; Brunstein, Elena; Issinger, Olaf-Georg


    . In contrast to the cyclins in the case of the cyclin-dependent kinases CK2beta is no on-switch of CK2alpha; rather the formation of the CK2 holoenzyme is accompanied with an overall change of the enzyme's profile including a modulation of the substrate specificity, an increase of the thermostability......, and an allocation of docking sites for membranes and other proteins. In this study we used C-terminal deletion variants of human CK2alpha and CK2beta that were enzymologically fully competent and in particular able to form a heterotetrameric holoenzyme. With differential scanning calorimetry (DSC) we confirmed...

  6. Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal. (United States)

    Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T; Gage, Fred H; Evans, Ronald M; Shi, Yanhong


    The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active beta-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.

  7. Regional and ethnic distribution of beta thalassemia mutations and effect of consanguinity in patients referred for prenatal diagnosis

    International Nuclear Information System (INIS)

    Hafeez, M.


    To determine the regional and ethnic distribution of beta thalassemia mutation and the effect of consanguinity in patients referred for prenatal diagnosis of beta b-thalassemia and to target the high risk population for screening. A total of 499 couples were referred to Gentec Lab., Lahore, from all over Pakistan for prenatal diagnosis of b-thalassemia. After counseling, chorionic villus sampling was done between 10-16 weeks of gestation. DNA analysis was done by Amplification Refractory Mutation System (ARMS) for type of mutation in the Armed Forces Institute of Pathology, Rawalpindi. Ethnicity, race and consanguineous relationship of parents was determined.b-thalassemia was prevalent in Punjabis (60.7%) followed by Saraikees (25.5%). Castewise it was most frequent in Rajputs followed by Jatts, Arain, Sheikhs and Pathans. 56.7% of the couples were first cousins and 19.8% were relatives. The commonest mutations were Frameshift 8-9 (Fr8-9) 33.5%, Intervening Sequence 1-5 (IVS 1-5) 17.2%, Fr4142 - 8%, IVS 1-1 - 5.2%, Deletion 619 (Del 619) 4.2% and Codon 5 (Cd 5) - 4.2%. In samples sent for analysis, 53.1% turned out to be carriers (trait), 25.3% were diseased (thalassemia major) and 21.6% were normal. P-value of all results was less than 0.001. In this series, the highest frequency was found in Punjabi Rajputs. The commonest mutation was Fr 8-9. Most parents were first cousins. Premarital thalassemia carrier testing can effectively reduce the disease. (author)

  8. Characterization of arrangement and expression of the beta-2 microglobulin locus in the sandbar and nurse shark. (United States)

    Chen, Hao; Kshirsagar, Sarika; Jensen, Ingvill; Lau, Kevin; Simonson, Caitlin; Schluter, Samuel F


    Beta 2 microglobulin (beta2m) is an essential subunit of major histocompatibility complex (MHC) type I molecules. In this report, beta2m cDNAs were identified and sequenced from sandbar shark spleen cDNA library. Sandbar shark beta2m gene encodes one amino acid less than most teleost beta2m genes, and 3 amino acids less than mammal beta2m genes. Although sandbar shark beta2m protein contains one beta sheet less than that of human in the predicted protein structure, the overall structure of beta2m proteins is conserved during evolution. Germline gene for the beta2m in sandbar and nurse shark is present as a single locus. It contains three exons and two introns. CpG sites are evenly distributed in the shark beta2m loci. Several DNA repeat elements were also identified in the shark beta2m loci. Sequence analysis suggests that the beta2m locus is not linked to the MHC I loci in the shark genome.

  9. Metabolic responses to pyruvate kinase deletion in lysine producing Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Wittmann Christoph


    Full Text Available Abstract Background Pyruvate kinase is an important element in flux control of the intermediate metabolism. It catalyzes the irreversible conversion of phosphoenolpyruvate into pyruvate and is under allosteric control. In Corynebacterium glutamicum, this enzyme was regarded as promising target for improved production of lysine, one of the major amino acids in animal nutrition. In pyruvate kinase deficient strains the required equimolar ratio of the two lysine precursors oxaloacetate and pyruvate can be achieved through concerted action of the phosphotransferase system (PTS and phosphoenolpyruvate carboxylase (PEPC, whereby a reduced amount of carbon may be lost as CO2 due to reduced flux into the tricarboxylic acid (TCA cycle. In previous studies, deletion of pyruvate kinase in lysine-producing C. glutamicum, however, did not yield a clear picture and the exact metabolic consequences are not fully understood. Results In this work, deletion of the pyk gene, encoding pyruvate kinase, was carried out in the lysine-producing strain C. glutamicum lysCfbr, expressing a feedback resistant aspartokinase, to investigate the cellular response to deletion of this central glycolytic enzyme. Pyk deletion was achieved by allelic replacement, verified by PCR analysis and the lack of in vitro enzyme activity. The deletion mutant showed an overall growth behavior (specific growth rate, glucose uptake rate, biomass yield which was very similar to that of the parent strain, but differed in slightly reduced lysine formation, increased formation of the overflow metabolites dihydroxyacetone and glycerol and in metabolic fluxes around the pyruvate node. The latter involved a flux shift from pyruvate carboxylase (PC to PEPC, by which the cell maintained anaplerotic supply of the TCA cycle. This created a metabolic by-pass from PEP to pyruvate via malic enzyme demonstrating its contribution to metabolic flexibility of C. glutamicum on glucose. Conclusion The metabolic

  10. Sigma beta decay

    International Nuclear Information System (INIS)

    Newman, D.E.


    Describes an experiment to measure beta decays of the sigma particle. Sigmas produced by stopping a K - beam in a liquid hydrogen target decayed in the following reactions: Kp → Σπ; Σ → Neν. The electron and pion were detected by wire spark chambers in a magnetic spectrometer and by plastic scintillators, and were differentiated by a threshold gas Cherenkov counter. The neutron was detected by liquid scintillation counters. The data (n = 3) shell electrons or the highly excited electrons decay first. Instead, it is suggested that when there are two to five electrons in highly excited states immediately after a heavy ion--atom collision the first transitions to occur will be among highly excited Rydberg states in a cascade down to the 4s, 4p, and 3d-subshells. If one of the long lived states becomes occupied by electrons promoted during the collision or by electrons falling from higher levels, it will not decay until after the valence shell decays. LMM rates calculated to test the methods used are compared to previous works. The mixing coefficients are given in terms of the states 4s4p, 45sp+-, and 5s5p. The applicability of Cooper, Fano, and Prats' discussion of the energies and transition rates of doubly excited states is considered

  11. Double Beta Decay

    International Nuclear Information System (INIS)

    Fiorini, Ettore


    The importance of neutrinoless Double Beta Decay (DBD) is stressed in view of the recent results of experiments on neutrino oscillations which indicate that the difference between the squared masses of two neutrinos of different flavours is finite [For a recent review including neutrino properties and recent results see: Review of Particle Physics, J. of Phys. G: Nuclear and Particle Physics 33, 1]. As a consequence the mass of at least one neutrino has to be different from zero and it becomes imperative to determine its absolute value. The various experimental techniques to search for DBD are discussed together with the difficult problems of the evaluation of the corresponding nuclear matrix elements. The upper limits on neutrino mass coming from the results of the various experiments are reported together with the indication for a non zero value by one of them not confirmed so far. The two presently running experiments on neutrinoless DBD are briefly described together with the already approved or designed second generation searches aiming to reach the values on the absolute neutrino mass indicated by the results on neutrino oscillations

  12. Comparative genomic analysis of the gut bacterium Bifidobacterium longum reveals loci susceptible to deletion during pure culture growth

    Directory of Open Access Journals (Sweden)

    Shakhova VV


    Full Text Available Abstract Background Bifidobacteria are frequently proposed to be associated with good intestinal health primarily because of their overriding dominance in the feces of breast fed infants. However, clinical feeding studies with exogenous bifidobacteria show they don't remain in the intestine, suggesting they may lose competitive fitness when grown outside the gut. Results To further the understanding of genetic attenuation that may be occurring in bifidobacteria cultures, we obtained the complete genome sequence of an intestinal isolate, Bifidobacterium longum DJO10A that was minimally cultured in the laboratory, and compared it to that of a culture collection strain, B. longum NCC2705. This comparison revealed colinear genomes that exhibited high sequence identity, except for the presence of 17 unique DNA regions in strain DJO10A and six in strain NCC2705. While the majority of these unique regions encoded proteins of diverse function, eight from the DJO10A genome and one from NCC2705, encoded gene clusters predicted to be involved in diverse traits pertinent to the human intestinal environment, specifically oligosaccharide and polyol utilization, arsenic resistance and lantibiotic production. Seven of these unique regions were suggested by a base deviation index analysis to have been precisely deleted from strain NCC2705 and this is substantiated by a DNA remnant from within one of the regions still remaining in the genome of NCC2705 at the same locus. This targeted loss of genomic regions was experimentally validated when growth of the intestinal B. longum in the laboratory for 1,000 generations resulted in two large deletions, one in a lantibiotic encoding region, analogous to a predicted deletion event for NCC2705. A simulated fecal growth study showed a significant reduced competitive ability of this deletion strain against Clostridium difficile and E. coli. The deleted region was between two IS30 elements which were experimentally

  13. The significance of chromosome deletions in atomic-bomb survivors

    International Nuclear Information System (INIS)

    Tanaka, Kimio; Shigeta, Chiharu; Oguma, Nobuo; Kamada, Nanao; Deng, Z.; Niimi, Masanobu; Aisaka, Tadaichi.


    In 39 A-bomb survivors 40 years after exposure at ≤ 1,000 m from ground zero, the frequency and features of chromosome deletions in peripheral lymphocytes were examined using a differential staining technique. Simultaneously, in vitro irradiation experiment with Cf-252 was made to infer chromosome aberrations occuring immediately after exposure. Californium-252 with 100 rad induced dicentric and ring chromosomes in 40 % of the cells and acentric fragments in 44 %. Among the A-bomb survivors, chromosome aberrations were observed in 651 (21 %) of the total 3,136 cells. There were 146 cells with deletions (22 % of abnormal cells; 5 % of the total cells), and 10 cells with acentric fragment (0.3 % of the total cells). The figure for deletions was far higher than that reported in the literature. A large number of deletions were seen in chromosomes no.4, no.21, and no.22, and a few deletions in chromosomes no.7 and no.20. Significance of chromosome deletions is discussed. (Namekawa, K.)

  14. Fast detection of deletion breakpoints using quantitative PCR

    Directory of Open Access Journals (Sweden)

    Gulshara Abildinova


    Full Text Available Abstract The routine detection of large and medium copy number variants (CNVs is well established. Hemizygotic deletions or duplications in the large Duchenne muscular dystrophy DMD gene responsible for Duchenne and Becker muscular dystrophies are routinely identified using multiple ligation probe amplification and array-based comparative genomic hybridization. These methods only map deleted or duplicated exons, without providing the exact location of breakpoints. Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. Here, we present a strategy for detecting the breakpoints of medium and large CNVs regardless of their size. The hemizygous deletion of exons 45-50 in the DMD gene and the large autosomal heterozygous PARK2 deletion were used to demonstrate the workflow that relies on real-time quantitative PCR to narrow down the deletion region and Sanger sequencing for breakpoint confirmation. The strategy is fast, reliable and cost-efficient, making it amenable to widespread use in genetic laboratories.

  15. Ocular Findings in Children With 22q11.2 Deletion Syndrome. (United States)

    Gokturk, Bahar; Topcu-Yilmaz, Pinar; Bozkurt, Banu; Yildirim, Mahmut Selman; Guner, Sukru Nail; Sayar, Esra Hazar; Reisli, Ismail


    To identify the ocular features of children diagnosed as having 22q11.2 deletion syndrome in a Turkish population, which is the most common microdeletion syndrome with a wide range of facial and ocular abnormalities. Sixteen children aged between 4 months and 18 years with a microdeletion in chromosome 22q11.2 underwent a detailed ophthalmological examination including uncorrected and best corrected visual acuity testing, stereoscopic vision examination, biomicroscopic and indirect fundus examination, and ocular motility testing. All patients had at least one ocular abnormality. The major abnormalities were eyelid abnormalities (eye hooding, narrow palpebral fissure, telecanthus, hypertelorism, sparse and thin eyebrows and eyelashes, blepharitis, and distichiasis), posterior embryotoxon, and tortuous retinal vessels in at least half of the patients. Other ophthalmological disorders were refractive errors, iris remnants, and strabismus. The chromosome 22q11.2 deletion syndrome is associated with a wide range of ocular disorders, which necessitates a comprehensive eye examination for appropriate treatment and follow-up. Ocular findings sometimes can provide a clue to the diagnosis of 22q11.2 deletion. [J Pediatr Ophthalmol Strabismus. 2016;53(4):218-222]. Copyright 2016, SLACK Incorporated.

  16. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Payne CM


    Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

  17. Systematic Identification of Determinants for Single-Strand Annealing-Mediated Deletion Formation in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Maia Segura-Wang


    Full Text Available To ensure genomic integrity, living organisms have evolved diverse molecular processes for sensing and repairing damaged DNA. If improperly repaired, DNA damage can give rise to different types of mutations, an important class of which are genomic structural variants (SVs. In spite of their importance for phenotypic variation and genome evolution, potential contributors to SV formation in Saccharomyces cerevisiae (budding yeast, a highly tractable model organism, are not fully recognized. Here, we developed and applied a genome-wide assay to identify yeast gene knockout mutants associated with de novo deletion formation, in particular single-strand annealing (SSA-mediated deletion formation, in a systematic manner. In addition to genes previously linked to genome instability, our approach implicates novel genes involved in chromatin remodeling and meiosis in affecting the rate of SSA-mediated deletion formation in the presence or absence of stress conditions induced by DNA-damaging agents. We closely examined two candidate genes, the chromatin remodeling gene IOC4 and the meiosis-related gene MSH4, which when knocked-out resulted in gene expression alterations affecting genes involved in cell division and chromosome organization, as well as DNA repair and recombination, respectively. Our high-throughput approach facilitates the systematic identification of processes linked to the formation of a major class of genetic variation.

  18. APC promoter 1B deletion in seven American families with familial adenomatous polyposis. (United States)

    Snow, A K; Tuohy, T M F; Sargent, N R; Smith, L J; Burt, R W; Neklason, D W


    Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome caused by mutations in the adenomatous polyposis coli (APC) gene. Clinical genetic testing fails to identify disease causing mutations in up to 20% of clinically apparent FAP cases. Following the inclusion of multiplex ligation-dependent probe amplification (MLPA) probes specific for APC promoter 1B, seven probands were identified with a deletion of promoter 1B. Using haplotype analysis spanning the APC locus, the seven families appear to be identical by descent from a common founder. The clinical phenotype of 19 mutation carriers is classical FAP with colectomy at an average age of 24. The majority of cases had a large number of duodenal and gastric polyps. Measurements of allele-specific expression of APC mRNA using TaqMan assay confirmed that relative expression in the allele containing the promoter 1B deletion was reduced 42-98%, depending on tissue type. This study confirms the importance of APC promoter deletions as a cause of FAP and identifies a founder mutation in FAP patients from the United States. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. (beta-HC CG) in

    African Journals Online (AJOL)


    Urothelial tumour samples were obtained from all the 86 patients requiring surgical ..... and/or urine beta HCG appears to be an efficient diagnostic marker for the ..... collected all urothelial tumour specimens for storage, cutting and staining.

  20. Beta-glucans and cholesterol

    Czech Academy of Sciences Publication Activity Database

    Šíma, Petr; Vannucci, Luca; Větvička, V.


    Roč. 41, č. 4 (2017), s. 1799-1808 ISSN 1107-3756 Institutional support: RVO:61388971 Keywords : cholesterol * beta-glucans * diet Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.341, year: 2016

  1. Radioisotope indicator, type BETA 2

    International Nuclear Information System (INIS)

    Duszanski, M.; Pankow, A.; Skwarczynski, B.


    The authors describe a radioisotope indicator, type BETA 2, constructed in the ZKMPW Works to be employed in mines for counting, checking, signalling the presence and positioning of cars, as well as monitoring the state of some other equipment. (author)

  2. Beta 1- and beta 2-adrenergic 125I-pindolol binding sites in the interpeduncular nucleus of the rat: Normal distribution and the effects of deafferentation

    International Nuclear Information System (INIS)

    Battisti, W.P.; Artymyshyn, R.P.; Murray, M.


    The plasticity of the beta 1- and beta 2-adrenergic receptor subtypes was examined in the interpeduncular nucleus (IPN) of the adult rat. The beta-adrenergic receptor antagonist 125I-pindolol (125I-PIN) was used in conjunction with the selective subtype antagonists ICI 118,551 and ICI 89,406 to determine the subnuclear distribution of beta 1- and beta 2-adrenergic receptors in this nucleus and to correlate the receptor distribution with the distribution of both noradrenergic afferents from the locus coeruleus (LC) and non-noradrenergic afferents from the fasiculus retroflexus (FR). The density of these binding sites was examined following lesions that decreased (LC lesions) or increased (FR lesions) the density of the noradrenergic projection in the IPN. Quantitative radioautography indicated that beta 1-labeled binding sites account for the larger percentage of binding sites in the IPN. The beta 1-binding sites are densest in those subnuclei that receive a noradrenergic projection from the LC: the central, rostral, and intermediate subnuclei. beta 1-binding sites are algo homogeneously distributed throughout the lateral subnuclei, where there is no detectable noradrenergic innervation. beta 2-binding sites have a more restricted distribution. They are concentrated in the ventral half of the lateral subnuclei, where they account for 70% of total 125I-PIN binding sites. beta 2-binding sites are also present along the ventral border of the IPN. Some of this labeling extends into the central and intermediate subnuclei. Bilateral lesions of the LC, which selectively remove noradrenergic innervation to the IPN, result in an increase in the beta 1-binding sites. Bilateral lesions of the FR, which remove the major cholinergic and peptidergic input from the IPN, elicit an increase in noradrenergic projections and a decrease in beta 1-binding sites

  3. Numt-mediated double-strand break repair mitigates deletions during primate genome evolution.

    Directory of Open Access Journals (Sweden)

    Einat Hazkani-Covo


    Full Text Available Non-homologous end joining (NHEJ is the major mechanism of double-strand break repair (DSBR in mammalian cells. NHEJ has traditionally been inferred from experimental systems involving induced double strand breaks (DSBs. Whether or not the spectrum of repair events observed in experimental NHEJ reflects the repair of natural breaks by NHEJ during chromosomal evolution is an unresolved issue. In primate phylogeny, nuclear DNA sequences of mitochondrial origin, numts, are inserted into naturally occurring chromosomal breaks via NHEJ. Thus, numt integration sites harbor evidence for the mechanisms that act on the genome over evolutionary timescales. We have identified 35 and 55 lineage-specific numts in the human and chimpanzee genomes, respectively, using the rhesus monkey genome as an outgroup. One hundred and fifty two numt-chromosome fusion points were classified based on their repair patterns. Repair involving microhomology and repair leading to nucleotide additions were detected. These repair patterns are within the experimentally determined spectrum of classical NHEJ, suggesting that information from experimental systems is representative of broader genetic loci and end configurations. However, in incompatible DSBR events, small deletions always occur, whereas in 54% of numt integration events examined, no deletions were detected. Numts show a statistically significant reduction in deletion frequency, even in comparison to DSBR involving filler DNA. Therefore, numts show a unique mechanism of integration via NHEJ. Since the deletion frequency during numt insertion is low, native overhangs of chromosome breaks are preserved, allowing us to determine that 24% of the analyzed breaks are cohesive with overhangs of up to 11 bases. These data represent, to the best of our knowledge, the most comprehensive description of the structure of naturally occurring DSBs. We suggest a model in which the sealing of DSBs by numts, and probably by other filler

  4. Bir1 Deletion Causes Malfunction of the Spindle Assembly Checkpoint and Apoptosis in Yeast

    International Nuclear Information System (INIS)

    Ren, Qun; Liou, Liang-Chun; Gao, Qiuqiang; Bao, Xiaoming; Zhang, Zhaojie


    Cell division in yeast is a highly regulated and well studied event. Various checkpoints are placed throughout the cell cycle to ensure faithful segregation of sister chromatids. Unexpected events, such as DNA damage or oxidative stress, cause the activation of checkpoint(s) and cell cycle arrest. Malfunction of the checkpoints may induce cell death. We previously showed that under oxidative stress, the budding yeast cohesin Mcd1, a homolog of human Rad21, was cleaved by the caspase-like protease Esp1. The cleaved Mcd1 C-terminal fragment was then translocated to mitochondria, causing apoptotic cell death. In the present study, we demonstrated that Bir1 plays an important role in spindle assembly checkpoint and cell death. Similar to H 2 O 2 treatment, deletion of BIR1 using a BIR1-degron strain caused degradation of the securin Pds1, which binds and inactivates Esp1 until metaphase-anaphase transition in a normal cell cycle. BIR1 deletion caused an increase level of ROS and mis-location of Bub1, a major protein for spindle assembly checkpoint. In wild type, Bub1 was located at the kinetochores, but was primarily in the cytoplasm in bir1 deletion strain. When BIR1 was deleted, addition of nocodazole was unable to retain the Bub1 localization on kinetochores, further suggesting that Bir1 is required to activate and maintain the spindle assembly checkpoint. Our study suggests that the BIR1 function in cell cycle regulation works in concert with its anti-apoptosis function.

  5. Delta-Beta Thalassaemia in a Pathan Family. (United States)

    Ahmad, Saqib Qayyum; Zafar, Saerah Iffat; Malik, Hamid Saeed; Ahmed, Suhaib


    Delta-beta-thalassaemia (δβ-thalassaemia) is a rare type of thalassaemia which mostly results from deletion of δ and β genes with preservation of γ genes. δβ-thalassaemia is classified into (δβ)+ and (δβ)0 types. The (δβ)0-thalassemia is further divided into GγAγ(δβ)0-thalassaemia and Gγ(Aγδβ)0-thalassaemia. In heterozygous state, (δβ)0mutations give rise to phenotype resembling β-thalassaemia trait but with raised Hb-F, ranging from 5 to 20%, without a rise in Hb-A2. In homozygotes, the clinical picture is usually that of thalassaemia intermedia and the patients have 100% Hb-F. Workup of a 1-year child suffering from pallor, chronic ill health, and splenomegaly referred to our laboratory with the suspicion of β-thalassaemia, ultimately resulted in a diagnosis on polymerase chain reaction as having homozygous inversion/deletion Gγ(Aγδβ)0-thalassaemia. Her family members were also investigated.

  6. TGF-beta1 modulates focal adhesion kinase expression in rat intestinal epithelial IEC-6 cells via stimulatory and inhibitory Smad binding elements. (United States)

    Walsh, Mary F; Ampasala, Dinakar R; Rishi, Arun K; Basson, Marc D


    TGF-beta and FAK modulate cell migration, differentiation, proliferation and apoptosis, and TGF-beta promotes FAK transcription in intestinal epithelial cells via Smad-dependent and independent pathways. We utilized a 1320 bp FAK promoter-luciferase construct to characterize basal and TGF-beta-mediated FAK gene transcription in IEC-6 cells. Inhibiting JNK or Akt negated TGF-beta-stimulated promoter activity; ERK inhibition did not block the TGF-beta effect but increased basal activity. Co-transfection with Co-Smad4 enhanced the TGF-beta response while the inhibitory Smad7 abolished it. Serial deletions sequentially removing the four Smad binding elements (SBE) in the 5' untranslated region of the promoter revealed that the two most distal SBE's are positive regulators while SBE3 exerts a negative influence. Mutational deletion of two upstream p53 sites enhanced basal but did not affect TGF-beta-stimulated increases in promoter activity. TGF-beta increased DNA binding of Smad4, phospho-Smad2/3 and Runx1/AML1a to the most distal 435 bp containing 3 SBE and 2 AML1a sites by ChIP assay. However, although point mutation of SBE1 ablated the TGF-beta-mediated rise in SV40-promoter activity, mutation of AML1a sites did not. TGF-beta regulation of FAK transcription reflects a complex interplay between positive and negative non-Smad signals and SBE's, the last independent of p53 or AML1a.

  7. 41 CFR 51-2.3 - Notice of proposed addition or deletion. (United States)


    ... addition or deletion. 51-2.3 Section 51-2.3 Public Contracts and Property Management Other Provisions... or deletion. At least 30 days prior to the Committee's consideration of the addition or deletion of a... Register announcing the proposed addition or deletion and providing interested persons an opportunity to...

  8. 10 CFR 9.19 - Segregation of exempt information and deletion of identifying details. (United States)


    ... 10 Energy 1 2010-01-01 2010-01-01 false Segregation of exempt information and deletion of... Information Act Regulations § 9.19 Segregation of exempt information and deletion of identifying details. (a... deletions are made from parts of the record by computer, the amount of information deleted will be indicated...

  9. Tables of double beta decay data

    Energy Technology Data Exchange (ETDEWEB)

    Tretyak, V.I. [AN Ukrainskoj SSR, Kiev (Ukraine)]|[Strasbourg-1 Univ., 67 (France). Centre de Recherches Nucleaires; Zdesenko, Y.G. [AN Ukrainskoj SSR, Kiev (Ukraine)


    A compilation of experimental data on double beta decay is presented. The tables contain the most stringent known experimental limits or positive results of 2{beta} transitions of 69 natural nuclides to ground and excited states of daughter nuclei for different channels (2{beta}{sup -}; 2{beta}{sup +}; {epsilon}{beta}{sup +}; 2{epsilon}) and modes (0{nu}; 2{nu}; 0{nu}M) of decay. (authors). 189 refs., 9 figs., 3 tabs.

  10. Beta Instability and Stochastic Market Weights


    David H. Goldenberg


    An argument is given for individual firm beta instability based upon the stochastic character of the market weights defining the market portfolio and the constancy of its beta. This argument is generalized to market weighted portfolios and the form of the stochastic process generating betas is linked to that of the market return process. The implications of this analysis for adequacy of models of beta nonstationarity and estimation of betas are considered in light of the available empirical e...

  11. Topological side-chain classification of beta-turns: ideal motifs for peptidomimetic development. (United States)

    Tran, Tran Trung; McKie, Jim; Meutermans, Wim D F; Bourne, Gregory T; Andrews, Peter R; Smythe, Mark L


    Beta-turns are important topological motifs for biological recognition of proteins and peptides. Organic molecules that sample the side chain positions of beta-turns have shown broad binding capacity to multiple different receptors, for example benzodiazepines. Beta-turns have traditionally been classified into various types based on the backbone dihedral angles (phi2, psi2, phi3 and psi3). Indeed, 57-68% of beta-turns are currently classified into 8 different backbone families (Type I, Type II, Type I', Type II', Type VIII, Type VIa1, Type VIa2 and Type VIb and Type IV which represents unclassified beta-turns). Although this classification of beta-turns has been useful, the resulting beta-turn types are not ideal for the design of beta-turn mimetics as they do not reflect topological features of the recognition elements, the side chains. To overcome this, we have extracted beta-turns from a data set of non-homologous and high-resolution protein crystal structures. The side chain positions, as defined by C(alpha)-C(beta) vectors, of these turns have been clustered using the kth nearest neighbor clustering and filtered nearest centroid sorting algorithms. Nine clusters were obtained that cluster 90% of the data, and the average intra-cluster RMSD of the four C(alpha)-C(beta) vectors is 0.36. The nine clusters therefore represent the topology of the side chain scaffold architecture of the vast majority of beta-turns. The mean structures of the nine clusters are useful for the development of beta-turn mimetics and as biological descriptors for focusing combinatorial chemistry towards biologically relevant topological space.

  12. The PDZ protein tax-interacting protein-1 inhibits beta-catenin transcriptional activity and growth of colorectal cancer cells. (United States)

    Kanamori, Mutsumi; Sandy, Peter; Marzinotto, Stefania; Benetti, Roberta; Kai, Chikatoshi; Hayashizaki, Yoshihide; Schneider, Claudio; Suzuki, Harukazu


    Wnt signaling is essential during development while deregulation of this pathway frequently leads to the formation of various tumors including colorectal carcinomas. A key component of the pathway is beta-catenin that, in association with TCF-4, directly regulates the expression of Wnt-responsive genes. To identify novel binding partners of beta-catenin that may control its transcriptional activity, we performed a mammalian two-hybrid screen and isolated the Tax-interacting protein (TIP-1). The in vivo complex formation between beta-catenin and TIP-1 was verified by coimmunoprecipitation, and a direct physical association was revealed by glutathione S-transferase pull-down experiments in vitro. By using a panel of deletion mutants of both proteins, we demonstrate that the interaction is mediated by the PDZ (PSD-95/DLG/ZO-1 homology) domain of TIP-1 and requires primarily the last four amino acids of beta-catenin. TIP-1 overexpression resulted in a dose-dependent decrease in the transcriptional activity of beta-catenin when tested on the TOP/FOPFLASH reporter system. Conversely, siRNA-mediated knock-down of endogenous TIP-1 slightly increased endogenous beta-catenin transactivation function. Moreover, we show that overexpression of TIP-1 reduced the proliferation and anchorage-independent growth of colorectal cancer cells. These data suggest that TIP-1 may represent a novel regulatory element in the Wnt/beta-catenin signaling pathway.

  13. Future of double beta decay and dark matter searches - GENIUS

    International Nuclear Information System (INIS)

    Klapdor-Kleingrothaus, H. V.; Baudis, L.; Heusser, G.; Krivosheina, I. V.; Kolb, S.; Majorovits, B.; Nabi, J.-U.; Paes, H.


    The recent results from the HEIDELBERG-MOSCOW experiment have demonstrated the large potential of double beta decay to search for new physics beyond the standard model. To increase further by a major step the present sensitivity for double beta decay and dark matter searches, we describe here a project, proposed recently [1], which would operate one tonne of 'naked' enriched germanium-detectors in liquid nitrogen as shielding in an underground set-up (GENIUS). It improves the sensitivity of neutrino masses to 0.01 eV. A 10 tonne version would probe neutrino masses even down to 10 -3 eV

  14. In-trap decay spectroscopy for {beta}{beta} decays

    Energy Technology Data Exchange (ETDEWEB)

    Brunner, Thomas


    The presented work describes the implementation of a new technique to measure electron-capture (EC) branching ratios (BRs) of intermediate nuclei in {beta}{beta} decays. This technique has been developed at TRIUMF in Vancouver, Canada. It facilitates one of TRIUMF's Ion Traps for Atomic and Nuclear science (TITAN), the Electron Beam Ion Trap (EBIT) that is used as a spectroscopy Penning trap. Radioactive ions, produced at the radioactive isotope facility ISAC, are injected and stored in the spectroscopy Penning trap while their decays are observed. A key feature of this technique is the use of a strong magnetic field, required for trapping. It radially confines electrons from {beta} decays along the trap axis while X-rays, following an EC, are emitted isotropically. This provides spatial separation of X-ray and {beta} detection with almost no {beta}-induced background at the X-ray detector, allowing weak EC branches to be measured. Furthermore, the combination of several traps allows one to isobarically clean the sample prior to the in-trap decay spectroscopy measurement. This technique has been developed to measure ECBRs of transition nuclei in {beta}{beta} decays. Detailed knowledge of these electron capture branches is crucial for a better understanding of the underlying nuclear physics in {beta}{beta} decays. These branches are typically of the order of 10{sup -5} and therefore difficult to measure. Conventional measurements suffer from isobaric contamination and a dominating {beta} background at theX-ray detector. Additionally, X-rays are attenuated by the material where the radioactive sample is implanted. To overcome these limitations, the technique of in-trap decay spectroscopy has been developed. In this work, the EBIT was connected to the TITAN beam line and has been commissioned. Using the developed beam diagnostics, ions were injected into the Penning trap and systematic studies on injection and storage optimization were performed. Furthermore, Ge

  15. Amino-acid composition after loop deletion drives domain swapping. (United States)

    Nandwani, Neha; Surana, Parag; Udgaonkar, Jayant B; Das, Ranabir; Gosavi, Shachi


    Rational engineering of a protein to enable domain swapping requires an understanding of the sequence, structural and energetic factors that favor the domain-swapped oligomer over the monomer. While it is known that the deletion of loops between β-strands can promote domain swapping, the spliced sequence at the position of the loop deletion is thought to have a minimal role to play in such domain swapping. Here, two loop-deletion mutants of the non-domain-swapping protein monellin, frame-shifted by a single residue, were designed. Although the spliced sequence in the two mutants differed by only one residue at the site of the deletion, only one of them (YEIKG) promoted domain swapping. The mutant containing the spliced sequence YENKG was entirely monomeric. This new understanding that the domain swapping propensity after loop deletion may depend critically on the chemical composition of the shortened loop will facilitate the rational design of domain swapping. © 2017 The Protein Society.

  16. The Yeast Deletion Collection: A Decade of Functional Genomics (United States)

    Giaever, Guri; Nislow, Corey


    The yeast deletion collections comprise >21,000 mutant strains that carry precise start-to-stop deletions of ∼6000 open reading frames. This collection includes heterozygous and homozygous diploids, and haploids of both MATa and MATα mating types. The yeast deletion collection, or yeast knockout (YKO) set, represents the first and only complete, systematically constructed deletion collection available for any organism. Conceived during the Saccharomyces cerevisiae sequencing project, work on the project began in 1998 and was completed in 2002. The YKO strains have been used in numerous laboratories in >1000 genome-wide screens. This landmark genome project has inspired development of numerous genome-wide technologies in organisms from yeast to man. Notable spinoff technologies include synthetic genetic array and HIPHOP chemogenomics. In this retrospective, we briefly describe the yeast deletion project and some of its most noteworthy biological contributions and the impact that these collections have had on the yeast research community and on genomics in general. PMID:24939991

  17. Molecular studies of deletions at the human steroid sulfatase locus

    International Nuclear Information System (INIS)

    Shapiro, L.J.; Yen, P.; Pomerantz, D.; Martin, E.; Rolewic, L.; Mohandas, T.


    The human steroid sulfatase gene (STS) is located on the distal X chromosome short arm close to the pseudoautosomal region but in a segment of DNA that is unique to the X chromosome. In contrast to most X chromosome-encoded genes, STS expression is not extinguished during the process of X chromosome inactivation. Deficiency of STS activity produced the syndrome of X chromosome-linked ichthyosis, which is one of the most common inborn errors of metabolism in man. Approximately 90% of STS - individuals have large deletions at the STS locus. The authors and others have found that the end points of such deletions are heterogeneous in their location. One recently ascertained subject was observed to have a 40-kilobase deletion that is entirely intragenic, permitting the cloning and sequencing of the deletion junction. Studies of this patient and of other X chromosome sequences in other subjects permit some insight into the mechanism(s) responsible for generating frequent deletions on the short arm of the X chromosome

  18. Sorting genomes by reciprocal translocations, insertions, and deletions. (United States)

    Qi, Xingqin; Li, Guojun; Li, Shuguang; Xu, Ying


    The problem of sorting by reciprocal translocations (abbreviated as SBT) arises from the field of comparative genomics, which is to find a shortest sequence of reciprocal translocations that transforms one genome Pi into another genome Gamma, with the restriction that Pi and Gamma contain the same genes. SBT has been proved to be polynomial-time solvable, and several polynomial algorithms have been developed. In this paper, we show how to extend Bergeron's SBT algorithm to include insertions and deletions, allowing to compare genomes containing different genes. In particular, if the gene set of Pi is a subset (or superset, respectively) of the gene set of Gamma, we present an approximation algorithm for transforming Pi into Gamma by reciprocal translocations and deletions (insertions, respectively), providing a sorting sequence with length at most OPT + 2, where OPT is the minimum number of translocations and deletions (insertions, respectively) needed to transform Pi into Gamma; if Pi and Gamma have different genes but not containing each other, we give a heuristic to transform Pi into Gamma by a shortest sequence of reciprocal translocations, insertions, and deletions, with bounds for the length of the sorting sequence it outputs. At a conceptual level, there is some similarity between our algorithm and the algorithm developed by El Mabrouk which is used to sort two chromosomes with different gene contents by reversals, insertions, and deletions.

  19. Differential roles of the glycogen-binding domains of beta subunits in regulation of the Snf1 kinase complex. (United States)

    Mangat, Simmanjeet; Chandrashekarappa, Dakshayini; McCartney, Rhonda R; Elbing, Karin; Schmidt, Martin C


    Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic alpha subunit and regulatory beta and gamma subunits. In this study, the role of the beta subunits in the regulation of Snf1 activity was examined. Yeasts express three isoforms of the AMP-activated protein kinase consisting of Snf1 (alpha), Snf4 (gamma), and one of three alternative beta subunits, either Sip1, Sip2, or Gal83. The Gal83 isoform of the Snf1 complex is the most abundant and was analyzed in the greatest detail. All three beta subunits contain a conserved domain referred to as the glycogen-binding domain. The deletion of this domain from Gal83 results in a deregulation of the Snf1 kinase, as judged by a constitutive activity independent of glucose availability. In contrast, the deletion of this homologous domain from the Sip1 and Sip2 subunits had little effect on Snf1 kinase regulation. Therefore, the different Snf1 kinase isoforms are regulated through distinct mechanisms, which may contribute to their specialized roles in different stress response pathways. In addition, the beta subunits are subjected to phosphorylation. The responsible kinases were identified as being Snf1 and casein kinase II. The significance of the phosphorylation is unclear since the deletion of the region containing the phosphorylation sites in Gal83 had little effect on the regulation of Snf1 in response to glucose limitation.

  20. Photochemical fate of beta-blockers in NOM enriched waters

    International Nuclear Information System (INIS)

    Wang, Ling; Xu, Haomin; Cooper, William J.; Song, Weihua


    Beta-blockers, prescribed for the treatment of high blood pressure and for long-term use after a heart attack, have been detected in surface and ground waters. This study examines the photochemical fate of three beta-blockers, atenolol, metoprolol, and nadolol. Hydrolysis accounted for minor losses of these beta-blockers in the pH range 4–10. The rate of direct photolysis at pH 7 in a solar simulator varied from 6.1 to 8.9 h −1 at pH 7. However, the addition of a natural organic matter (NOM) isolate enhanced the photochemical loss of all three compounds. Indirect photochemical fate, generally described by reactions with hydroxyl radical (·OH) and singlet oxygen ( 1 ΔO 2 ), and, the direct reaction with the triplet excited state, 3 NOM ⁎ , also varied but collectively appeared to be the major loss factor. Bimolecular reaction rate constants of the three beta-blockers with 1 ΔO 2 and ·OH were measured and accounted for 0.02–0.04% and 7.2–38.9% of their loss, respectively. These data suggest that the 3 NOM ⁎ contributed 50.6–85.4%. Experiments with various 3 NOM ⁎ quenchers supported the hypothesis that it was singly the most important reaction. Atenolol was chosen for more detailed investigation, with the photoproducts identified by LC–MS analysis. The results suggested that electron-transfer could be an important mechanism in photochemical fate of beta-blockers in the presence of NOM. - Highlights: ► Photochemical degradation of beta-blockers in the simulated natural waters. ► Reactive Oxygen Species play a minor role in the indirect photodegradation. ► The loss of beta-blockers results from direct reaction with 3 DOM ⁎ .

  1. The physiology of rodent beta-cells in pancreas slices. (United States)

    Rupnik, M


    Beta-cells in pancreatic islets form complex syncytia. Sufficient cell-to-cell electrical coupling seems to ensure coordinated depolarization pattern and insulin release that can be further modulated by rich innervation. The complex structure and coordinated action develop after birth during fast proliferation of the endocrine tissue. These emergent properties can be lost due to various reasons later in life and can lead to glucose intolerance and diabetes mellitus. Pancreas slice is a novel method of choice to study the physiology of beta-cells still embedded in their normal cellulo-social context. I present major advantages, list drawbacks and provide an overview on recent advances in our understanding of the physiology of beta-cells using the pancreas slice approach.

  2. Topographic Beta Spiral and Onshore Intrusion of the Kuroshio Current (United States)

    Yang, De-Zhou; Huang, Rui Xin; Yin, Bao-shu; Feng, Xing-Ru; Chen, Hai-ying; Qi, Ji-Feng; Xu, Ling-jing; Shi, Yun-long; Cui, Xuan; Gao, Guan-Dong; Benthuysen, Jessica A.


    The Kuroshio intrusion plays a vitally important role in carrying nutrients to marginal seas. However, the key mechanism leading to the Kuroshio intrusion remains unclear. In this study we postulate a mechanism: when the Kuroshio runs onto steep topography northeast of Taiwan, the strong inertia gives rise to upwelling over topography, leading to a left-hand spiral in the stratified ocean. This is called the topographic beta spiral, which is a major player regulating the Kuroshio intrusion; this spiral can be inferred from hydrographic surveys. In the world oceans, the topographic beta spirals can be induced by upwelling generated by strong currents running onto steep topography. This is a vital mechanism regulating onshore intruding flow and the cross-shelf transport of energy and nutrients from the Kuroshio Current to the East China Sea. This topographic beta spiral reveals a long-term missing link between the oceanic general circulation theory and shelf dynamic theory.

  3. BCL2-like 11 intron 2 deletion polymorphism is not associated with non-small cell lung cancer risk and prognosis. (United States)

    Cho, Eun Na; Kim, Eun Young; Jung, Ji Ye; Kim, Arum; Oh, In Jae; Kim, Young Chul; Chang, Yoon Soo


    BCL2-Like 11(BIM), which encodes a BH3-only protein, is a major pro-apoptotic molecule that facilitates cell death. We hypothesized that a BIM intron 2 deletion polymorphism increases lung cancer risk and predicts poor prognosis in non-small lung cancer (NSCLC) patients. We prospectively recruited 450 lung cancer patients and 1:1 age, sex, and smoking status matched control subjects from February 2013 to April 2014 among patients treated at Severance, Gangnam Severance, and Chonnam Hwasoon Hospital. The presence of a 2903-bp genomic DNA deletion polymorphism of intron 2 of BIM was analyzed by PCR and validated by sequencing. Odds ratios were calculated by chi-square tests and survival analysis with Kaplan-Meier estimation. Sixty-nine out of 450 (15.3%) lung cancer patients carried the BIM deletion polymorphism, while 66 out of 450 (14.7%) control subjects carried the BIM deletion polymorphism, with an odds ratio of for lung cancer of 1.054 (95% CI; 0.731-1.519). We categorized 406 NSCLC patients according to the presence of the polymorphism and found that there were no statistically significant differences in age, sex, histologic type, or stage between subjects with and without the deletion polymorphism. The BIM deletion polymorphism did not influence overall survival (OS) or progression free survival (PFS) in our sample (OS; 37.6 vs 34.4 months (P=0.759), PFS; 49.6 vs 26.0 months (P=0.434)). These findings indicate that the BIM deletion polymorphism is common in Korean NSCLC patients but does not significantly affect the intrinsic biologic function of BH3-only protein. Furthermore, the BIM deletion polymorphism did not predict clinical outcomes in patients with NSCLC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Plasmid-mediated AmpC-type beta-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum beta-lactams, including moxalactam. (United States)

    Horii, T; Arakawa, Y; Ohta, M; Ichiyama, S; Wacharotayankun, R; Kato, N


    Klebsiella pneumoniae NU2936 was isolated from a patient and was found to produce a plasmid-encoded beta-lactamase (MOX-1) which conferred resistance to broad spectrum beta-lactams, including moxalactam, flomoxef, ceftizoxime, cefotaxime, and ceftazidime. Resistance could be transferred from K. pneumoniae NU2936 to Escherichia coli CSH2 by conjugation with a transfer frequency of 5 x 10(-7). The structural gene of MOX-1 (blaMOX-1) was cloned and expressed in E. coli HB101. The MIC of moxalactam for E. coli HB101 producing MOX-1 was > 512 micrograms/ml. The apparent molecular mass and pI of this enzyme were calculated to be 38 kDa and 8.9, respectively. Hg2+ and Cu2+ failed to block enzyme activity, and the presence of EDTA in the reaction buffer did not reduce the enzyme activity. However, clavulanate and cloxacillin, serine beta-lactamase inhibitors, inhibited the enzyme activity competitively (Kis = 5.60 and 0.35 microM, respectively). The kinetic study of MOX-1 suggested that it effectively hydrolyzed broad-spectrum beta-lactams. A hybridization study confirmed that blaMOX-1 is encoded on a large resident plasmid (pRMOX1; 180 kb) of strain NU2936. By deletion analysis, the functional region was localized within a 1.2-kb region of the plasmid. By amino acid sequencing, 18 of 33 amino acid residues at the N terminus of MOX-1 were found to be identical to those of Pseudomonas aeruginosa AmpC. These findings suggest that MOX-1 is a plasmid-mediated AmpC-type beta-lactamase that provides enteric bacteria resistance to broad-spectrum beta-lactams, including moxalactam. Images PMID:8517725

  5. Smart Beta or Smart Alpha

    DEFF Research Database (Denmark)

    Winther, Kenneth Lillelund; Steenstrup, Søren Resen


    that smart beta investing probably will do better than passive market capitalization investing over time, we believe many are coming to a conclusion too quickly regarding active managers. Institutional investors are able to guide managers through benchmarks and risk frameworks toward the same well......Smart beta has become the flavor of the decade in the investment world with its low fees, easy access to rewarded risk premiums, and appearance of providing good investment results relative to both traditional passive benchmarks and actively managed funds. Although we consider it well documented......-documented smart beta risk premiums and still motivate active managers to avoid value traps, too highly priced small caps, defensives, etc. By constructing the equity portfolios of active managers that resemble the most widely used risk premiums, we show that the returns and risk-adjusted returns measures...

  6. A Rare Syndrome of Deletion in 2 Siblings

    Directory of Open Access Journals (Sweden)

    Aravindhan Veerapandiyan MBBS


    Full Text Available The Glutamate receptor, ionotropic, delta 2 gene codes for an ionotropic glutamate delta-2 receptor, which is selectively expressed in cerebellar Purkinje cells, and facilitates cerebellar synapse organization and transmission. The phenotype associated with the deletion of Glutamate receptor, ionotropic, delta 2 gene in humans was initially defined in 2013. In this case report, the authors describe 2 brothers who presented with developmental delay, tonic upward gaze, nystagmus, oculomotor apraxia, hypotonia, hyperreflexia, and ataxia. They were found to have a homozygous intragenic deletion within the Glutamate receptor, ionotropic, delta 2 gene at exon 2. Our patients serve as an addition to the literature of previously reported children with this rare clinical syndrome associated with Glutamate receptor, ionotropic, delta 2 deletion.

  7. A local-world node deleting evolving network model

    International Nuclear Information System (INIS)

    Gu Yuying; Sun Jitao


    A new type network growth rule which comprises node addition with the concept of local-world connectivity and node deleting is studied. A series of theoretical analysis and numerical simulation to the LWD network are conducted in this Letter. Firstly, the degree distribution p(k) of this network changes no longer pure scale free but truncates by an exponential tail and the truncation in p(k) increases as p a decreases. Secondly, the connectivity is tighter, as the local-world size M increases. Thirdly, the average path length L increases and the clustering coefficient decreases as generally node deleting increases. Finally, trends up when the local-world size M increases, so as to k max . Hence, the expanding local-world can compensate the infection of the node deleting

  8. A local-world node deleting evolving network model

    Energy Technology Data Exchange (ETDEWEB)

    Gu Yuying [Department of Mathematics, Tongji University, Shanghai 200092 (China); Sun Jitao [Department of Mathematics, Tongji University, Shanghai 200092 (China)], E-mail:


    A new type network growth rule which comprises node addition with the concept of local-world connectivity and node deleting is studied. A series of theoretical analysis and numerical simulation to the LWD network are conducted in this Letter. Firstly, the degree distribution p(k) of this network changes no longer pure scale free but truncates by an exponential tail and the truncation in p(k) increases as p{sub a} decreases. Secondly, the connectivity is tighter, as the local-world size M increases. Thirdly, the average path length L increases and the clustering coefficient decreases as generally node deleting increases. Finally, trends up when the local-world size M increases, so as to k{sub max}. Hence, the expanding local-world can compensate the infection of the node deleting.

  9. Monoamine oxidase deficiency in males with an X chromosome deletion. (United States)

    Sims, K B; de la Chapelle, A; Norio, R; Sankila, E M; Hsu, Y P; Rinehart, W B; Corey, T J; Ozelius, L; Powell, J F; Bruns, G


    Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.

  10. SIRT6-mediated transcriptional suppression of Txnip is critical for pancreatic beta cell function and survival in mice. (United States)

    Qin, Kunhua; Zhang, Ning; Zhang, Zhao; Nipper, Michael; Zhu, Zhenxin; Leighton, Jake; Xu, Kexin; Musi, Nicolas; Wang, Pei


    Better understanding of how genetic and epigenetic components control beta cell differentiation and function is key to the discovery of novel therapeutic approaches to prevent beta cell dysfunction and failure in the progression of type 2 diabetes. Our goal was to elucidate the role of histone deacetylase sirtuin 6 (SIRT6) in beta cell development and homeostasis. Sirt6 endocrine progenitor cell conditional knockout and beta cell-specific knockout mice were generated using the Cre-loxP system. Mice were assayed for islet morphology, glucose tolerance, glucose-stimulated insulin secretion and susceptibility to streptozotocin. Transcriptional regulatory functions of SIRT6 in primary islets were evaluated by RNA-Seq analysis. Reverse transcription-quantitative (RT-q)PCR and immunoblot were used to verify and investigate the gene expression changes. Chromatin occupancies of SIRT6, H3K9Ac, H3K56Ac and active RNA polymerase II were evaluated by chromatin immunoprecipitation. Deletion of Sirt6 in pancreatic endocrine progenitor cells did not affect endocrine morphology, beta cell mass or insulin production but did result in glucose intolerance and defective glucose-stimulated insulin secretion in mice. Conditional deletion of Sirt6 in adult beta cells reproduced the insulin secretion defect. Loss of Sirt6 resulted in aberrant upregulation of thioredoxin-interacting protein (TXNIP) in beta cells. SIRT6 deficiency led to increased acetylation of histone H3 lysine residue at 9 (H3K9Ac), acetylation of histone H3 lysine residue at 56 (H3K56Ac) and active RNA polymerase II at the promoter region of Txnip. SIRT6-deficient beta cells exhibited a time-dependent increase in H3K9Ac, H3K56Ac and TXNIP levels. Finally, beta cell-specific SIRT6-deficient mice showed increased sensitivity to streptozotocin. Our results reveal that SIRT6 suppresses Txnip expression in beta cells via deacetylation of histone H3 and plays a critical role in maintaining beta cell function and viability

  11. Microarray data analyses of yeast RNA Pol I subunit RPA12 deletion strain

    Directory of Open Access Journals (Sweden)

    Kamlesh Kumar Yadav


    Full Text Available The ribosomal RNA (rRNA biosynthesis is the most energy consuming process in all living cells and the majority of total transcription activity is dedicated for synthesizing rRNA. The cells may adjust the synthesis of rRNA with the availability of resources. rRNA is mainly synthesized by RNA polymerase I that is composed of 14 subunits. Deletion of RPA12, 14, 39 and 49 are viable. RPA12 is a very small protein (13.6 kDa, and the amount of protein in the cells is very high (12,000 molecules per cell, but the role of this protein is unknown in other cellular metabolic processes (Kulak et al., 2014 [1]. RPA12 consists of two zinc-binding domains and it is required for the termination of rRNA synthesis (Mullem et al., 2002 [2]. Deletions of RPA12 in Saccharomyces cerevisiae and Schizosaccharomyces pombe cause a conditional growth defect (Nogi et al., 1993 [3]. In S. pombe, C-terminal deletion behaves like wild-type (Imazawa et al., 2001 [4]. This prompted us to investigate in detail the physiological role of RPA12 in S. cerevisiae, we performed the microarray of rpa12∆ strain and deposited into Gene Expression Omnibus under GSE68731. The analysis of microarray data revealed that the expression of major cellular metabolism genes is high. The amino acid biosynthesis, nonpolar lipid biosynthesis and glucose metabolic genes are highly expressed. The analyses also revealed that the rpa12∆ cells have an uncontrolled synthesis of cell metabolites, so RPA12 could be a master regulator for whole cellular metabolism.

  12. The diagnosis and molecular analysis of a novel 21.9kb deletion (Qinzhou type deletion) causing α+ thalassemia. (United States)

    Long, Ju; Yan, Shanhuo; Lao, Kegan; Pang, Wanrong; Ye, Xuehe; Sun, Lei


    α-Thalassemia is a common single-gene genetic disease that can cause Hb Bart's hydrops fetalis and Hb H disease in tropical and subtropical regions. When examining conventional thalassemia genes, an only detected --(SEA) genotype sample needs further analysis. In doing so, we found a novel 21.9kb deletion (Qinzhou type deletion). The deletion position of the novel 21.9kb deletion is from 14373bp to 36299bp of the α-globin gene cluster (NG_000006.1); thus, there exists a 21927bp sequence deletion, into which a 29bp sequence is added. After sequence analysis, a group of Gap-PCR primers were synthesized to diagnose this novel thalassemia genotype. Through pedigree analysis, we deduced that the propositus obtained the novel alleles from her mother. The genotype of this propositus is --(SEA)/-α(21.9) and its phenotype conforms to the characteristics of Hb H disease, establishing that the combination between -α(21.9) genotype and α(0) genotype can lead to Hb H disease. By molecular analysis, we established that this case fits the characteristic of an α(+) thalassemia genotype. © 2013.

  13. Telomere healing following DNA polymerase arrest-induced breakages is likely the main mechanism generating chromosome 4p terminal deletions. (United States)

    Hannes, Femke; Van Houdt, Jeroen; Quarrell, Oliver W; Poot, Martin; Hochstenbach, Ron; Fryns, Jean-Pierre; Vermeesch, Joris R


    Constitutional developmental disorders are frequently caused by terminal chromosomal deletions. The mechanisms and/or architectural features that might underlie those chromosome breakages remain largely unexplored. Because telomeres are the vital DNA protein complexes stabilizing linear chromosomes against chromosome degradation, fusion, and incomplete replication, those terminal-deleted chromosomes acquired new telomeres either by telomere healing or by telomere capture. To unravel the mechanisms leading to chromosomal breakage and healing, we sequenced nine chromosome 4p terminal deletion boundaries. A computational analysis of the breakpoint flanking region, including 12 previously published pure terminal breakage sites, was performed in order to identify architectural features that might be involved in this process. All terminal 4p truncations were likely stabilized by telomerase-mediated telomere healing. In the majority of breakpoints multiple genetic elements have a potential to induce secondary structures and an enrichment in replication stalling site motifs were identified. These findings suggest DNA replication stalling-induced chromosome breakage during early development is the first mechanistic step leading toward terminal deletion syndromes. © 2010 Wiley-Liss, Inc.

  14. Immune Modulation of NYVAC-Based HIV Vaccines by Combined Deletion of Viral Genes that Act on Several Signalling Pathways

    Directory of Open Access Journals (Sweden)

    Carmen Elena Gómez


    Full Text Available An HIV-1 vaccine continues to be a major target to halt the AIDS pandemic. The limited efficacy of the RV144 phase III clinical trial with the canarypox virus-based vector ALVAC and a gp120 protein component led to the conclusion that improved immune responses to HIV antigens are needed for a more effective vaccine. In non-human primates, the New York vaccinia virus (NYVAC poxvirus vector has a broader immunogenicity profile than ALVAC and has been tested in clinical trials. We therefore analysed the HIV immune advantage of NYVAC after removing viral genes that act on several signalling pathways (Toll-like receptors—TLR—interferon, cytokines/chemokines, as well as genes of unknown immune function. We generated a series of NYVAC deletion mutants and studied immune behaviour (T and B cell to HIV antigens and to the NYVAC vector in mice. Our results showed that combined deletion of selected vaccinia virus (VACV genes is a valuable strategy for improving the immunogenicity of NYVAC-based vaccine candidates. These immune responses were differentially modulated, positive or negative, depending on the combination of gene deletions. The deletions also led to enhanced antigen- or vector-specific cellular and humoral responses. These findings will facilitate the development of optimal NYVAC-based vaccines for HIV and other diseases.

  15. Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru (United States)

    Akinyi, Sheila; Hayden, Tonya; Gamboa, Dionicia; Torres, Katherine; Bendezu, Jorge; Abdallah, Joseph F.; Griffing, Sean M.; Quezada, Wilmer Marquiño; Arrospide, Nancy; De Oliveira, Alexandre Macedo; Lucas, Carmen; Magill, Alan J.; Bacon, David J.; Barnwell, John W.; Udhayakumar, Venkatachalam


    The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times. PMID:24077522

  16. Beta decay of 22O

    International Nuclear Information System (INIS)

    Hubert, F.; Dufour, J.P.; Moral, R. del; Fleury, A.; Jean, D.; Pravikoff, M.S.; Delagrange, H.; Geissel, H.; Schmidt, K.H.; Hanelt, E.


    The beta-gamma spectroscopic study of 22 O is presented. This nucleus, produced as a projectile-like fragment from the interaction of a 60 MeV/n 40 Ar beam with a Be target, has been separated by the LISE spectrometer. Several gamma rays from 22 O decay have been observed, from which a half-life of (2.25±0.15) s has been determined. Accurate excitation energies have been deduced for several states in 22 F. A partial beta decay scheme of 22 O has been established. Experimental results have been compared with shell model calculations. (orig.)

  17. Beta-hemolytic Streptococcal Bacteremia

    DEFF Research Database (Denmark)

    Nielsen, Hans Ulrik; Kolmos, Hans Jørn; Frimodt-Møller, Niels


    Bacteremia with beta-hemolytic Streptococci groups A, B, C and G has a mortality rate of approximately 20%. In this study we analyzed the association of various patient risk factors with mortality. Records from 241 patients with beta-hemolytic streptococcal bacteremia were reviewed with particular...... attention to which predisposing factors were predictors of death. A logistic regression model found age, burns, immunosuppressive treatment and iatrogenic procedures prior to the infection to be significant predictors of death, with odds ratios of 1.7 (per decade), 19.7, 3.6 and 6.8, respectively...

  18. The Beta Transmuted Weibull Distribution

    Directory of Open Access Journals (Sweden)

    Manisha Pal


    Full Text Available The paper introduces a beta transmuted Weibull distribution, which contains a number ofdistributions as special cases. The properties of the distribution are discussed and explicit expressions are derived for the mean deviations, Bonferroni and Lorenz curves, and reliability. The distribution and moments of order statistics are also studied. Estimation of the model parameters by the method of maximum likelihood is discussed. The log beta transmuted Weibull model is introduced to analyze censored data. Finally, the usefulness of the new distribution in analyzing positive data is illustrated.

  19. Beta activity of enriched uranium

    International Nuclear Information System (INIS)

    Nambiar, P.P.V.J.; Ramachandran, V.


    Use of enriched uranium as reactor fuel necessitates its handling in various forms. For purposes of planning and organising radiation protection measures in enriched uranium handling facilities, it is necessary to have a basic knowledge of the radiation status of enriched uranium systems. The theoretical variations in beta activity and energy with U 235 enrichment are presented. Depletion is considered separately. Beta activity build up is also studied for two specific enrichments, in respect of which experimental values for specific alpha activity are available. (author)

  20. Metabolic clearance rate and urinary clearance of purified beta-core

    International Nuclear Information System (INIS)

    Wehmann, R.E.; Blithe, D.L.; Flack, M.R.; Nisula, B.C.


    We injected a highly purified preparation of the beta-core molecule, a fragment of hCG beta excreted in pregnancy urine, into five men and three women to determine its kinetic parameters, MCR, and urinary clearance. The beta-core molecule was distributed in an initial volume [1950 +/- 156 (mean +/- SEM) mL/m2 body surface area] approximately equal to the estimated plasma volume. Its disappearance was multiexponential on a semilogarithmic plot, with a rapid phase t1/2 of 3.5 +/- 0.7 min and a slow phase t1/2 of 22.4 +/- 4.2 min. The transit time (the mean time spent by a molecule of beta-core in transit) was 20.6 +/- 2.1 min. The MCR was 192.0 +/- 8.0 mL/min.m2 body surface area. About 5% of the injected dose of beta-core was excreted into the urine in the first 30 min after injection, and low levels of excretion persisted for up to 7 days. The urinary clearance rate of beta-core was 13.7 +/- 1.4 mL/min.m2, accounting for about 8% of the elimination of beta-core from the plasma. The beta-core immunoreactivity in serum and urine was characterized by gel filtration and three independent RIA systems to show that its properties were indistinguishable from those of the injected beta-core. Serum levels of beta-core in pregnant women were less than 0.2 ng/mL, while the amounts excreted in their urine were as much as 5 mg/day. Based on these clearance parameters of beta-core in normal subjects, less than 0.2% of the beta-core excreted in pregnancy urine is derived by urinary clearance of plasma beta-core. Therefore, more than 99% of the beta-core excreted in pregnancy urine is derived from beta-core in a compartment separate from plasma. In particular, these data indicate that there is relatively little placental secretion of beta-core into plasma and that placental secretion does not account for the vast majority of beta-core in pregnancy urine

  1. A {beta} - {gamma} coincidence; Metodo de coincidencias {beta} - {gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Agullo, F


    A {beta} - {gamma} coincidence method for absolute counting is given. The fundamental principles are revised and the experimental part is detailed. The results from {sup 1}98 Au irradiated in the JEN 1 Swimming pool reactor are given. The maximal accuracy is 1 per cent. (Author) 11 refs.

  2. Pseudotumor of the pituitary due to PROP-1 deletion. (United States)

    Teinturier, C; Vallette, S; Adamsbaum, C; Bendaoud, M; Brue, T; Bougnères, P F


    Hypopituitarism associated with pituitary mass in childhood is most frequently the consequence of craniopharyngioma or Rathke's cleft cyst. We report a patient with an intrasellar pseudotumor associated with hypopituitarism, which led us to a misdiagnosis of intrasellar craniopharyngioma. After spontaneous involution of the mass, diagnosis was revised. DNA analysis showed a deletion in the Prophet of Pit-1 (PROP-1) gene, a pituitary transcription factor. It is important to recognize that a PROP-1 deletion can cause pituitary pseudotumor that can be mistaken for a craniopharyngioma or Rathke's pouch cyst.

  3. Evidence for novel beta-sheet structures in Iowa mutant beta-amyloid fibrils. (United States)

    Tycko, Robert; Sciarretta, Kimberly L; Orgel, Joseph P R O; Meredith, Stephen C


    Asp23-to-Asn mutation within the coding sequence of beta-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-Abeta40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-Abeta40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10(-3) min(-1) and 1.07 x 10(-4) min(-1) for D23N-Abeta40 and the wild-type peptide WT-Abeta40, respectively) and without a lag phase. Electron microscopy shows that D23N-Abeta40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-beta pattern, with a sharp reflection at 4.7 A and a broad reflection at 9.4 A, which is notably smaller than the value for WT-Abeta40 fibrils (10.4 A). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-Abeta40 fibrils containing the in-register, parallel beta-sheet structure commonly found in WT-Abeta40 fibrils and most other amyloid fibrils. Antiparallel beta-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through (13)C-(13)C and (15)N-(13)C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-Abeta40 fibrils and the unusual vasculotropic clinical picture in these patients.

  4. N-Benzylhydroxylamine addition to beta-aryl enoates. Enantioselective synthesis of beta-aryl-beta-amino acid precursors (United States)

    Sibi; Liu


    Chiral Lewis acid catalyzed N-benzylhydroxylamine addition to pyrrolidinone-derived enoates afforded beta-aryl-beta-amino acid derivatives in high enantiomeric purity with moderate to very good chemical efficiency.

  5. Thalassemia major and consanguinity in Shiraz city, Iran. (United States)

    Asadi-Pooya, Ali Akbar; Doroudchi, Mehrnoosh


    Beta-thalassemia is among the most common genetic disorders in the world and in Iran, with widespread occurrence. A cross-sectional study on 648 beta-thalassemia patients in Shiraz, Iran was carried out to determine the demography of beta-thalassemia major in Shiraz city, Fars province, Iran and also the rate of consanguinity and the significance of pre-marriage counseling in decreasing familial marriages and consequently preventing this autosomal recessive genetic disease. All interviewed patients had thalassemia major and their age, sex, and the consanguinity between parents were recorded. 40.6% of beta-thalassemia patients were outcomes of first-cousin marriages. Comparison of the percentages of familial marriages (consanguinity) between parents of beta-thalassemia patients and a sample of normal population, revealed a statistically significant difference (pmarriages among thalassemic families, however, more education and awareness of young women and men about the increased risk of beta-thalassemia after familial marriage through pre-marriage counseling is still necessary.

  6. Small mosaic deletion encompassing the snoRNAs and SNURF-SNRPN results in an atypical Prader-Willi syndrome phenotype. (United States)

    Anderlid, Britt-Marie; Lundin, Johanna; Malmgren, Helena; Lehtihet, Mikael; Nordgren, Ann


    Genetic analyses were performed in a male patient with suspected Prader-Willi syndrome who presented with hypogonadism, excessive eating, central obesity, small hands and feet and cognition within the low normal range. However, he had no neonatal hypotonia or feeding problems during infancy. Chromosome analysis showed a normal male karyotype. Further analysis with array-CGH identified a mosaic 847 kb deletion in 15q11-q13, including SNURF-SNRPN, the snoRNA gene clusters SNORD116 (HBII-85), SNORD115, (HBII-52), SNORD109 A and B (HBII-438A and B), SNORD64 (HBII-13), and NPAP1 (C15ORF2). MLPA confirmed the deletion and the results were compatible with a paternal origin. Metaphase-FISH verified the mosaicism with the deletion present in 58% of leukocytes analyzed. Three smaller deletions in this region have previously been reported in patients with Prader-Willi syndrome phenotype. All three deletions included SNORD116, but only two encompassed parts of SNURF-SNRPN, implicating SNORD116 as the major contributor to the Prader-Willi phenotype. Our case adds further information about genotype-phenotype correlation and supports the hypothesis that SNORD116 plays a major role in the pathogenesis of Prader-Willi syndrome. Furthermore, it examplifies diagnostic difficulties in atypical cases and illustrates the need for additional testing methods when Prader-Willi syndrome is suspected. © 2013 Wiley Periodicals, Inc.

  7. Electret dosemeter for beta radiation

    International Nuclear Information System (INIS)

    Campos, L.L.; Caldas, L.V.E.; Mascarenhas, S.

    The response characteristics of an electret dosemeter for beta radiation are studied. Experiments were performed using different geometries and walls, and it was verified for which geometry the dosemeter sensitivity is greater. Sources of 90 Sr - 90 Y, 204 Tl and 85 Kr were used in the experiments. (I.C.R.) [pt

  8. Personnel monitoring for beta rays

    International Nuclear Information System (INIS)

    Piesch, E.; Johns, T.F.


    The practical considerations which have to be taken into account in the design of personnel monitors intended to measure doses resulting from exposure to beta rays are discussed. These include the measurement of doses in situations involving either fairly uniform or non-uniform irradiation and of doses to the male gonads. (UK)

  9. Constraining neutrinoless double beta decay

    International Nuclear Information System (INIS)

    Dorame, L.; Meloni, D.; Morisi, S.; Peinado, E.; Valle, J.W.F.


    A class of discrete flavor-symmetry-based models predicts constrained neutrino mass matrix schemes that lead to specific neutrino mass sum-rules (MSR). We show how these theories may constrain the absolute scale of neutrino mass, leading in most of the cases to a lower bound on the neutrinoless double beta decay effective amplitude.

  10. Beta Cell Workshop 2013 Kyoto

    DEFF Research Database (Denmark)

    Heller, R Scott; Madsen, Ole D; Nielsen, Jens Høiriis


    The very modern Kyoto International Conference Center provided the site for the 8th workshop on Beta cells on April 23-26, 2013. The preceding workshops were held in Boston, USA (1991); Kyoto, Japan (1994); Helsingør, Denmark (1997); Helsinki, Finland (2003); El Perello, Spain (2006); Peebles...

  11. [Perissodactyla: the primary structure of hemoglobins from the lowland tapir (Tapirus terrestris): glutamic acid in position 2 of the beta chains]. (United States)

    Mazur, G; Braunitzer, G


    The hemoglobins from a lowland tapir (Tapirus terrestris) were analysed and the complete primary structure is described. The globin chains were separated on CM cellulose column in 8M urea and the amino-acid sequences were determined in the liquid phase sequenator. The results show that globin consists of two alpha chains (alpha I and alpha II) and beta major and beta minor components. The alpha chains differ only at one position: alpha I contains aspartic acid and alpha II glycine. The beta chains are heterogeneous: aspartic and glutamic acid were found at position beta 21 and beta 73 of the beta major components and asparagine and serine at position beta 139. In the beta minor components four positions were found with more than one amino acid, namely beta 2, beta 4, beta 6 and beta 56. The sequences are compared with those of man, horse and rhinoceros. Four residues of horse methemoglobin, which are involved in the alpha 1 beta 1 contacts are substituted in tapir hemoglobins. In the alpha chains: alpha 107(G14)Ser----Val, alpha 111-(G18) Val----Leu, alpha 115(GH3) Asn----Asp or Gly; in the beta chains: beta 116(G18) Arg----Gln. The amino acid at beta 2 of the major components is glutamic acid while glutamine and histidine are found in the minor components. Although glutamic acid, a binding site for ATP, does not interact with 2,3-bisphosphoglycerate, glutamine and histidine in the minor components are responsible for the slight effect of 2,3-bisphosphoglycerate on tapir hemoglobin.

  12. Beta calibration and dosimetry at IPEN

    International Nuclear Information System (INIS)

    Caldas, L.V.E.


    A commercial extrapolation chamber (PTW, Germany) was tested in different beta radiation fields and its properties investigated. Its usefullness for beta radiation calibration and dosimetry was demonstrated. (Author) [pt

  13. Illegitimate V(D)J recombination-mediated deletions in Notch1 and Bcl11b are not sufficient for extensive clonal expansion and show minimal age or sex bias in frequency or junctional processing

    Energy Technology Data Exchange (ETDEWEB)

    Champagne, Devin P., E-mail:; Shockett, Penny E., E-mail:


    Highlights: • Examines illegitimate V(D)J deletion junctions in Notch1 and Bcl11b. • Suggests little influence of deletions alone on clonal outgrowth in wild-type mice. • No age or sex biases in frequency, clonality, or junctional processing observed. • Contrasts with previous results at TCRβ and HPRT1 loci. • Deletions in Bcl11b may be tolerated more easily than those in Notch1. - Abstract: Illegitimate V(D)J recombination at oncogenes and tumor suppressor genes is implicated in formation of several T cell malignancies. Notch1 and Bcl11b, genes involved in developing T cell specification, selection, proliferation, and survival, were previously shown to contain hotspots for deletional illegitimate V(D)J recombination associated with radiation-induced thymic lymphoma. Interestingly, these deletions were also observed in wild-type animals. In this study, we conducted frequency, clonality, and junctional processing analyses of Notch1 and Bcl11b deletions during mouse development and compared results to published analyses of authentic V(D)J rearrangements at the T cell receptor beta (TCRβ) locus and illegitimate V(D)J deletions observed at the human, nonimmune HPRT1 locus not involved in T cell malignancies. We detect deletions in Notch1 and Bcl11b in thymic and splenic T cell populations, consistent with cells bearing deletions in the circulating lymphocyte pool. Deletions in thymus can occur in utero, increase in frequency between fetal and postnatal stages, are detected at all ages examined between fetal and 7 months, exhibit only limited clonality (contrasting with previous results in radiation-sensitive mouse strains), and consistent with previous reports are more frequent in Bcl11b, partially explained by relatively high Recombination Signal Information Content (RIC) scores. Deletion junctions in Bcl11b exhibit greater germline nucleotide loss, while in Notch1 palindromic (P) nucleotides are more abundant, although average P nucleotide length is

  14. Deletion Mutagenesis and Identification of Causative Mutations in Maize. (United States)

    Jia, Shangang; Li, Aixia; Zhang, Chi; Holding, David


    We describe a method for gamma-irradiation of mature maize seeds to generate mutants with opaque endosperm and reduced kernel fill phenotypes. We also describe methods for mapping mutants and identifying causal gene mutations. Using this method, a population of 1788M2 families and 47 Mo17 × F2s showing stable, segregating, and viable kernel phenotypes was developed. For molecular characterization of the mutants, we utilized a novel functional genomics platform that combines separate Bulked Segregant RNA and exome sequencing data sets (BSREx-seq) to map causative mutations and identify candidate genes within mapping intervals. We also describe the use of exome capture sequencing of F2 mutant and normal pools to perform mapping and candidate gene identification without the need for separate RNA-seq (BSEx-seq). To exemplify the utility of the deletion mutants for functional genomics and provide proof-of-concept for the bioinformatics platform, we summarize the identification of the causative deletion in two mutants. Mutant 937, which was characterized by BSREx-seq, harbors a 6203-bp in-frame deletion covering six exons within the Opaque-1 gene on chromosome 4. Preliminary investigation of opaque mutant 1486 with BSEx-seq shows a tight mapping interval and associated deletion on chromosome 10.

  15. Genetics Home Reference: 22q13.3 deletion syndrome (United States)

    ... 5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How are genetic ... Veltman JA, de Vries BB. Molecular characterisation of patients with subtelomeric 22q ... L, Enns GM, Hoyme HE. Terminal 22q deletion syndrome: a newly recognized cause of ...

  16. 78 FR 21348 - Procurement List; Additions and Deletions; Recissions (United States)


    ... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Additions and Deletions; Recissions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Rescission of Previous Procurement List Decision. SUMMARY: The Committee for Purchase...

  17. Genetics Home Reference: 2q37 deletion syndrome (United States)

    ... on PubMed or Free article on PubMed Central Casas KA, Mononen TK, Mikail CN, Hassed SJ, Li S, ... 2005 Aug 18. Citation on PubMed Falk RE, Casas KA. Chromosome 2q37 deletion: clinical and molecular aspects. ...

  18. The detection of large deletions or duplications in genomic DNA. (United States)

    Armour, J A L; Barton, D E; Cockburn, D J; Taylor, G R


    While methods for the detection of point mutations and small insertions or deletions in genomic DNA are well established, the detection of larger (>100 bp) genomic duplications or deletions can be more difficult. Most mutation scanning methods use PCR as a first step, but the subsequent analyses are usually qualitative rather than quantitative. Gene dosage methods based on PCR need to be quantitative (i.e., they should report molar quantities of starting material) or semi-quantitative (i.e., they should report gene dosage relative to an internal standard). Without some sort of quantitation, heterozygous deletions and duplications may be overlooked and therefore be under-ascertained. Gene dosage methods provide the additional benefit of reporting allele drop-out in the PCR. This could impact on SNP surveys, where large-scale genotyping may miss null alleles. Here we review recent developments in techniques for the detection of this type of mutation and compare their relative strengths and weaknesses. We emphasize that comprehensive mutation analysis should include scanning for large insertions and deletions and duplications. Copyright 2002 Wiley-Liss, Inc.

  19. 78 FR 24733 - Procurement List, Additions and Deletions (United States)


    ... Purchase From People Who Are Blind or Severely Disabled published notices of proposed additions to the... Services Administration. Portable Desktop Clipboard, 9\\1/2\\ W x 1\\1/2\\ D x 13\\1/2\\ H NSN: 7510-00-NIB-2133... for Purchase From People Who Are Blind or Severely Disabled published notices of proposed deletions...

  20. 76 FR 35415 - Procurement List; Proposed Additions and Deletions (United States)


    ... Command, Natick, MA. SERVICE: Service Type/Location: Laundry Services, Department of Veterans Affairs... proposing to add products and a service to the Procurement List that will be furnished by nonprofit agencies employing persons who are blind or have other severe disabilities, and deletes products and a service...

  1. 76 FR 14942 - Procurement List; Additions and Deletions (United States)


    ... DFAC. Service Type/Location: Laundry & Dry Cleaning Service, F.E. Warren, AFB, WY. NPA: Goodwill... Service Type/Location: Laundry Service, Atlanta VA Medical Center, Decatur, GA. NPA: GINFL Services, Inc...: Additions to and deletions from the Procurement List. SUMMARY: This action adds services to the Procurement...

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    ... Customs and Border Protection, Office of Procurement, Washington, DC Service Type/Locations: Laundry.../Locations: Laundry Service, Naval Hospital System, 2800 Child Street, Jacksonville, FL NPA: GINFL Services...: Additions to and deletion from the Procurement List. SUMMARY: This action adds products and services to the...

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    .... Services Service Type/Location: Laundry and Dry Cleaning Service, Buckley Air Force Base Lodging & Medical... products and services to the Procurement List that will be furnished by nonprofit agencies employing persons who are blind or have other severe disabilities, and deletes a service previously provided by such...

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    ... Investigation, Washington, DC Service Type/Location: Laundry Service, Stratton Medical Center, 113 Holland Ave... persons who are blind or have other severe disabilities, and deletes services previously furnished by such... entities to furnish the services to the Government. 3. There are no known regulatory alternatives which...

  5. Induced pluripotent stem cells with a pathological mitochondrial DNA deletion (United States)

    Cherry, Anne B. C.; Gagne, Katelyn E.; McLoughlin, Erin M.; Baccei, Anna; Gorman, Bryan; Hartung, Odelya; Miller, Justine D.; Zhang, Jin; Zon, Rebecca L.; Ince, Tan A.; Neufeld, Ellis J.; Lerou, Paul H.; Fleming, Mark D.; Daley, George Q.; Agarwal, Suneet


    In congenital mitochondrial DNA (mtDNA) disorders, a mixture of normal and mutated mtDNA (termed heteroplasmy) exists at varying levels in different tissues, which determines the severity and phenotypic expression of disease. Pearson marrow pancreas syndrome (PS) is a congenital bone marrow failure disorder caused by heteroplasmic deletions in mtDNA. The cause of the hematopoietic failure in PS is unknown, and adequate cellular and animal models are lacking. Induced pluripotent stem (iPS) cells are particularly amenable for studying mtDNA disorders, as cytoplasmic genetic material is retained during direct reprogramming. Here we derive and characterize iPS cells from a patient with PS. Taking advantage of the tendency for heteroplasmy to change with cell passage, we isolated isogenic PS-iPS cells without detectable levels of deleted mtDNA. We found that PS-iPS cells carrying a high burden of deleted mtDNA displayed differences in growth, mitochondrial function, and hematopoietic phenotype when differentiated in vitro, compared to isogenic iPS cells without deleted mtDNA. Our results demonstrate that reprogramming somatic cells from patients with mtDNA disorders can yield pluripotent stem cells with varying burdens of heteroplasmy that might be useful in the study and treatment of mitochondrial diseases. PMID:23400930

  6. 78 FR 17641 - Procurement List; Proposed Addition and Deletion (United States)


    ... People Who Are Blind or Severely Disabled, 1401 S. Clarke Street, Suite 10800, Arlington, Virginia 22202... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Addition and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION...

  7. 78 FR 45183 - Procurement List; Proposed Addition and Deletions (United States)


    ... People Who Are Blind or Severely Disabled, 1401 S. Clark Street, Suite 10800, Arlington, Virginia, 22202... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Addition and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled...

  8. 78 FR 68823 - Procurement List Proposed Additions and Deletions (United States)


    ... for Purchase From People Who Are Blind or Severely Disabled, 1401 S. Clark Street, Suite 10800... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Proposed Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled...

  9. 78 FR 32631 - Procurement List; Proposed Additions and Deletions (United States)


    ... People Who Are Blind or Severely Disabled, 1401 S. Clark Street, Suite 10800, Arlington, Virginia 22202... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions and Deletions AGENCY: Committee for Purchase from People Who are Blind or Severely Disabled...

  10. 78 FR 43180 - Procurement List; Proposed Additions and Deletions (United States)


    ... for Purchase From People Who Are Blind or Severely Disabled, 1401 S. Clark Street, Suite 10800... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions and Deletions AGENCY: Committee for Purchase from People Who Are Blind or Severely Disabled...

  11. Angiotensin-converting enzyme insertion/deletion gene ...

    Indian Academy of Sciences (India)

    Angiotensin-converting enzyme insertion/deletion gene polymorphism in cystic fibrosis patients. Sabrine Oueslati Sondess Hadj Fredj Hajer Siala Amina Bibi Hajer Aloulou Lamia Boughamoura Khadija Boussetta Sihem Barsaoui Taieb Messaoud. Research Note Volume 95 Issue 1 March 2016 pp 193-196 ...

  12. The insertion/deletion polymorphism of angiotensin-converting ...

    African Journals Online (AJOL)

    The association between type 2 diabetes mellitus (T2DM) and essential hypertension (EH) is not well understood. Both conditions result from an interaction of multiple genetic (ethnic) and environmental (geographical) factors. One possible genetic determinant is the angiotensin-converting enzyme (ACE) insertion/deletion ...

  13. Oncolytic Replication of E1b-Deleted Adenoviruses

    Directory of Open Access Journals (Sweden)

    Pei-Hsin Cheng


    Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

  14. Remarks on Causative Verbs and Object Deletion in English (United States)

    Onozuka, Hiromi


    Rappaport Hovav and Levin [Rappaport Hovav, M., Levin, B., 1998. "Building verb meanings." In: Butt, M., Geuder, W. (Eds.), "The Projection of Arguments: Lexical and Compositional Factors." CSLI Publications, Stanford, pp. 97-134] contend that result verbs disallow object deletion because of their lexical semantic properties. Their point is that…

  15. [An updated review of 1p36 deletion (monosomy) syndrome]. (United States)

    Bello, Sabina; Rodríguez-Moreno, Antonio

    The Monosomy 1p36 deletion syndrome is part of the group of diseases known as Rare Diseases. The objective of the present work is to review the characteristics of Monosomy 1p36 deletion syndrome. The monosomy 1p36 deletion syndrome phenotype includes: dysmorphic craniofacial features; large anterior fontanelle, unibrow, deep-set eyes, epicanthus, wide nasal root/bridge, mandible hypoplasia, abnormal location of the pinna, philtrum and pointed chin; neurological alterations: seizures and hydrocephalus (in some cases). Cerebral malformations: ventricular hypertrophy, increased subarachnoid space, morphological alterations of corpus callosum, cortical atrophy, delays in myelinisation, periventricular leukomalacia and periventricular heterotopia. These alterations produce intellectual disability and delays in motor growth, communication skills, language, social and adaptive behaviour. It is Hearing and vision impairments are also observed in subjects with this syndrome, as well as alterations of cardiac, endocrine and urinary systems and alterations at skin and skeletal level. Approximately 100 cases have been documented since 1981. This rare disease is the most common subtelomeric-micro-deletion syndrome. In situ hybridization with fluorescence (FISH) and array-comparative genomic hybridization (CGH-array) are at present the two best diagnostic techniques. There is currently no effective medical treatment for this disease. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. 78 FR 73503 - Procurement List Additions and Deletions (United States)


    ... by the General Services Administration. NSN: MR 376--Resealable Bags, Holiday, 6.5'' x 5.875''. NSN..., Holiday, 24PC. NPA: Winston-Salem Industries for the Blind, Inc., Winston-Salem, NC. Contracting Activity... disabilities, and deletes a product and services from the Procurement List previously furnished by such...

  17. Genetics Home Reference: distal 18q deletion syndrome (United States)

    ... 18q deletion syndrome chromosome 18q monosomy chromosome 18q- syndrome De Grouchy syndrome del(18q) syndrome monosomy 18q Related Information How ... MS, Tienari PJ, Wirtavuori KO, Valanne LK. 18q-syndrome: brain MRI shows poor differentiation of gray and white matter on ... RL, Hale DE, Rose SR, Leach RJ, Cody JD. The spectrum ...

  18. Construction of a psb C deletion strain in Synechocystis 6803. (United States)

    Goldfarb, N; Knoepfle, N; Putnam-Evans, C


    Synechocystis 6803 is a cyanobacterium that carries out-oxygenic photosynthesis. We are interested in the introduction of mutations in the large extrinsic loop region of the CP43 protein of Photosystem II (PSII). CP43 appears to be required for the stable assembly of the PSII complex and also appears to play a role in photosynthetic oxygen evolution. Deletion of short segments of the large extrinsic loop results in mutants incapable of evolving oxygen. Alterations in psbC, the gene encoding CP43, are introduced into Synechocystis 6803 by transformation and homologous recombination. Specifically, plasmid constructs bearing the site-directed mutations are introduced into a deletion strain where the portion of the gene encoding the area of mutation has been deleted and replaced by a gene conferring antibiotic resistance. We have constructed a deletion strain of Synechocystis appropriate for the introduction of mutations in the large extrinsic loop of CP43 and have used it successfully to produce site-directed mutants.

  19. 77 FR 60969 - Procurement List; Proposed Additions and Deletions (United States)


    ...., Wichita, KS. Contracting Activity: Defense Logistics Agency Troop Support, Philadelphia, PA. Coverage: C-List for 100% of the requirement of the Department of Defense, as aggregated by the Defense Logistics...., Portsmouth, VA. Contracting Activity: Dept. of the Army, W071 Endist Kansas City, Kansas City, MO. Deletions...

  20. Frequency of heterozygous TET2 deletions in myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Joseph Tripodi


    Full Text Available Joseph Tripodi1, Ronald Hoffman1, Vesna Najfeld2, Rona Weinberg31The Myeloproliferative Disorders Program, Tisch Cancer Institute, Department of Medicine and 2Department of Medicine and Pathology, Mount Sinai School of Medicine, 3The Myeloproliferative Disorders Program, Cellular Therapy Laboratory, The New York Blood Center, New York, NY, USAAbstract: The Philadelphia chromosome (Ph-negative myeloproliferative neoplasms (MPNs, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a group of clonal hematopoietic stem cell disorders with overlapping clinical and cytogenetic features and a variable tendency to evolve into acute leukemia. These diseases not only share overlapping chromosomal abnormalities but also a number of acquired somatic mutations. Recently, mutations in a putative tumor suppressor gene, ten-eleven translocation 2 (TET2 on chromosome 4q24 have been identified in 12% of patients with MPN. Additionally 4q24 chromosomal rearrangements in MPN, including TET2 deletions, have also been observed using conventional cytogenetics. The goal of this study was to investigate the frequency of genomic TET2 rearrangements in MPN using fluorescence in situ hybridization as a more sensitive method for screening and identifying genomic deletions. Among 146 MPN patients, we identified two patients (1.4% who showed a common 4q24 deletion, including TET2. Our observations also indicated that the frequency of TET2 deletion is increased in patients with an abnormal karyotype (5%.Keywords: TET2, myeloproliferative neoplasms, fluorescence in situ hybridization, cytogenetics