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Sample records for bloom syndrome protein

  1. Bloom syndrome.

    Science.gov (United States)

    Arora, Harleen; Chacon, Anna H; Choudhary, Sonal; McLeod, Michael P; Meshkov, Lauren; Nouri, Keyvan; Izakovic, Jan

    2014-07-01

    Bloom Syndrome (BS, MIM #210900) is an autosomal recessive genetic disorder caused by a mutation in the BLM gene, which codes for the DNA repair enzyme RecQL3 helicase. Without proper DNA repair mechanisms, abnormal DNA exchange takes place between sister chromatids and results in genetic instability that may lead to cancer, especially lymphoma and acute myelogenous leukemia, lower and upper gastrointestinal tract neoplasias, cutaneous tumors, and neoplasias in the genitalia and urinary tract. BS patients are usually of Ashkenazi Jewish descent and exhibit narrow facial features, elongated limbs, and several dermatologic complications including photosensitivity, poikiloderma, and telangiectatic erythema. The most concerning manifestation of BS is multiple malignancies, which require frequent screenings and strict vigilance by the physician. Therefore, distinguishing between BS and other dermatologic syndromes of similar presentation such as Rothmund-Thomson Syndrome, Erythropoietic Protoporphyria, and Cockayne Syndrome is paramount to disease management and to prolonging life. BS can be diagnosed through a variety of DNA sequencing methods, and genetic testing is available for high-risk populations. This review consolidates several sources on BS sequelae and aims to suggest the importance of differentiating BS from other dermatologic conditions. This paper also elucidates the recently discovered BRAFT and FANCM protein complexes that link BS and Fanconi anemia.

  2. Critical interaction domains between bloom syndrome protein and RAD51.

    Science.gov (United States)

    Bergeron, Krystal L; Murphy, Eileen L; Brown, Lily W; Almeida, Karen H

    2011-01-01

    The American Cancer Society's 2009 statistics estimate that 1 out of every 4 deaths is cancer related. Genomic instability is a common feature of cancerous states, and an increase in genomic instability is the diagnostic feature of Bloom Syndrome. Bloom Syndrome, a rare disorder characterized by a predisposition to cancer, is caused by mutations of the BLM gene. This study focuses on the partnerships of BLM protein to RAD51, a Homologous Recombination repair protein essential for survival. A systematic set of BLM deletion fragments were generated to refine the protein binding domains of BLM to RAD51 and determine interacting regions of BLM and ssDNA. Results show that RAD51 and ssDNA interact in overlapping regions; BLM₁₀₀₋₂₁₄ and BLM₁₃₁₇₋₁₃₆₇. The overlapping nature of these regions suggests a preferential binding for one partner that could function to regulate homologous recombination and therefore helps to clarify the role of BLM in maintaining genomic stability.

  3. Loss of Bloom syndrome protein destabilizes human gene cluster architecture.

    Science.gov (United States)

    Killen, Michael W; Stults, Dawn M; Adachi, Noritaka; Hanakahi, Les; Pierce, Andrew J

    2009-09-15

    Bloom syndrome confers strong predisposition to malignancy in multiple tissue types. The Bloom syndrome patient (BLM) protein defective in the disease biochemically functions as a Holliday junction dissolvase and human cells lacking functional BLM show 10-fold elevated rates of sister chromatid exchange. Collectively, these phenomena suggest that dysregulated mitotic recombination drives the genomic instability underpinning the development of cancer in these individuals. Here we use physical analysis of the highly repeated, highly self-similar human ribosomal RNA gene clusters as sentinel biomarkers for dysregulated homologous recombination to demonstrate that loss of BLM protein function causes a striking increase in spontaneous molecular level genomic restructuring. Analysis of single-cell derived sub-clonal populations from wild-type human cell lines shows that gene cluster architecture is ordinarily very faithfully preserved under mitosis, but is so unstable in cell lines derived from BLMs as to make gene cluster architecture in different sub-clonal populations essentially unrecognizable one from another. Human cells defective in a different RecQ helicase, the WRN protein involved in the premature aging Werner syndrome, do not exhibit the gene cluster instability (GCI) phenotype, indicating that the BLM protein specifically, rather than RecQ helicases generally, holds back this recombination-mediated genomic instability. An ataxia-telangiectasia defective cell line also shows elevated rDNA GCI, although not to the extent of BLM defective cells. Genomic restructuring mediated by dysregulated recombination between the abundant low-copy repeats in the human genome may prove to be an important additional mechanism of genomic instability driving the initiation and progression of human cancer.

  4. Telomere-binding Protein TRF2 Binds to and Stimulates the Werner and Bloom Syndrome Helicases

    National Research Council Canada - National Science Library

    Patricia L. Opresko; Cayetano von Kobbe; Jean-Philippe Laine; Jeanine Harrigan; Ian D. Hickson; Vilhelm A. Bohr

    2002-01-01

    .... This interaction is mediated by the RecQ conserved C-terminal region of WRN. In vitro , TRF2 demonstrates high affinity for WRN and for another RecQ family member, the Bloom syndrome protein (BLM...

  5. The Werner syndrome protein is distinguished from the Bloom syndrome protein by its capacity to tightly bind diverse DNA structures.

    Science.gov (United States)

    Kamath-Loeb, Ashwini; Loeb, Lawrence A; Fry, Michael

    2012-01-01

    Loss of Werner syndrome helicase-exonuclease (WRN) or of its homolog Bloom syndrome helicase (BLM) results in different inherited disorders. Whereas Werner syndrome is characterized by premature onset of aging and age-associated diseases, Bloom syndrome involves developmental abnormalities and increased predisposition to diverse malignancies. To identify biochemical differences between WRN and BLM that might contribute to the dissimilar outcomes of their loss, we compared their abilities to unwind and bind in vitro diverse DNA structures. Full-length recombinant WRN and BLM proteins expressed in and purified from Sf9 insect cells unwound to comparable extents and with similar K(m) values partial DNA duplex, splayed arm DNA and G'2 bimolecular quadruplex DNA. However, WRN resolved bubble DNA ∼25-fold more efficiently than BLM. The two enzymes were mainly distinguished by their contrasting abilities to bind DNA. WRN bound partial duplexes, bubble and splayed arm DNA and G'2 bimolecular and G4 four-molecular quadruplexes with dissociation constants of 0.25 to 25 nM. By contrast, BLM formed substantial complexes with only G4 quadruplex DNA while binding only marginally other DNA structures. We raise the possibility that in addition to its enzymatic activities WRN may act as a scaffold for the assembly on DNA of additional DNA processing proteins.

  6. The Werner syndrome protein is distinguished from the Bloom syndrome protein by its capacity to tightly bind diverse DNA structures.

    Directory of Open Access Journals (Sweden)

    Ashwini Kamath-Loeb

    Full Text Available Loss of Werner syndrome helicase-exonuclease (WRN or of its homolog Bloom syndrome helicase (BLM results in different inherited disorders. Whereas Werner syndrome is characterized by premature onset of aging and age-associated diseases, Bloom syndrome involves developmental abnormalities and increased predisposition to diverse malignancies. To identify biochemical differences between WRN and BLM that might contribute to the dissimilar outcomes of their loss, we compared their abilities to unwind and bind in vitro diverse DNA structures. Full-length recombinant WRN and BLM proteins expressed in and purified from Sf9 insect cells unwound to comparable extents and with similar K(m values partial DNA duplex, splayed arm DNA and G'2 bimolecular quadruplex DNA. However, WRN resolved bubble DNA ∼25-fold more efficiently than BLM. The two enzymes were mainly distinguished by their contrasting abilities to bind DNA. WRN bound partial duplexes, bubble and splayed arm DNA and G'2 bimolecular and G4 four-molecular quadruplexes with dissociation constants of 0.25 to 25 nM. By contrast, BLM formed substantial complexes with only G4 quadruplex DNA while binding only marginally other DNA structures. We raise the possibility that in addition to its enzymatic activities WRN may act as a scaffold for the assembly on DNA of additional DNA processing proteins.

  7. Structure of the RecQ C-terminal domain of human Bloom syndrome protein.

    Science.gov (United States)

    Kim, Sun-Yong; Hakoshima, Toshio; Kitano, Ken

    2013-11-21

    Bloom syndrome is a rare genetic disorder characterized by genomic instability and cancer predisposition. The disease is caused by mutations of the Bloom syndrome protein (BLM). Here we report the crystal structure of a RecQ C-terminal (RQC) domain from human BLM. The structure reveals three novel features of BLM RQC which distinguish it from the previous structures of the Werner syndrome protein (WRN) and RECQ1. First, BLM RQC lacks an aromatic residue at the tip of the β-wing, a key element of the RecQ-family helicases used for DNA-strand separation. Second, a BLM-specific insertion between the N-terminal helices exhibits a looping-out structure that extends at right angles to the β-wing. Deletion mutagenesis of this insertion interfered with binding to Holliday junction. Third, the C-terminal region of BLM RQC adopts an extended structure running along the domain surface, which may facilitate the spatial positioning of an HRDC domain in the full-length protein.

  8. Solution structure of the HRDC domain of human Bloom syndrome protein BLM.

    Science.gov (United States)

    Sato, Akiko; Mishima, Masaki; Nagai, Aki; Kim, Sun-Yong; Ito, Yutaka; Hakoshima, Toshio; Jee, Jun-Goo; Kitano, Ken

    2010-10-01

    Bloom syndrome is a rare genetic disorder characterized by severe growth retardation and cancer predisposition. The disease is caused by a loss of function of the Bloom syndrome protein (BLM), a member of the RecQ family of DNA helicases. Here we report on the first 3D structure of a BLM fragment, a solution structure of the C-terminal helicase-and-ribonuclease D-C-terminal (HRDC) domain from human BLM. The structure reveals unique features of BLM HRDC that are distinct from the HRDC domain of Werner syndrome protein. In particular, BLM HRDC retains many acidic residues exposed to the solvent, which makes the domain surface extensively electronegative. Consistent with this, fluorescence polarization assays showed an inability of isolated BLM HRDC to interact with DNA substrates. Analyses employing ultracentrifugation, gel-filtration, CD spectroscopy and dynamic light scattering showed that the BLM HRDC domain exists as a stable monomer in solution. The results show that BLM HRDC is a compact, robust and acidic motif which may play a distinct role apart from DNA binding.

  9. Identification and analysis of new proteins involved in the DNA damage response network of Fanconi anemia and Bloom syndrome.

    Science.gov (United States)

    Guo, Rong; Xu, Dongyi; Wang, Weidong

    2009-05-01

    The use of co-immunoprecipitation (co-IP) to purify multi-protein complexes has contributed greatly to our understanding of the DNA damage response network associated with Fanconi anemia (FA), Bloom syndrome (BS) and breast cancer. Four new FA genes and two new protein partners for the Bloom syndrome gene product have been identified by co-IP. Here, we discuss our experience in using co-IP and other techniques to isolate and characterize new FA and BS-related proteins.

  10. RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability.

    Science.gov (United States)

    Xu, Dongyi; Guo, Rong; Sobeck, Alexandra; Bachrati, Csanad Z; Yang, Jay; Enomoto, Takemi; Brown, Grant W; Hoatlin, Maureen E; Hickson, Ian D; Wang, Weidong

    2008-10-15

    BLM, the helicase mutated in Bloom syndrome, associates with topoisomerase 3alpha, RMI1 (RecQ-mediated genome instability), and RPA, to form a complex essential for the maintenance of genome stability. Here we report a novel component of the BLM complex, RMI2, which interacts with RMI1 through two oligonucleotide-binding (OB)-fold domains similar to those in RPA. The resulting complex, named RMI, differs from RPA in that it lacks obvious DNA-binding activity. Nevertheless, RMI stimulates the dissolution of a homologous recombination intermediate in vitro and is essential for the stability, localization, and function of the BLM complex in vivo. Notably, inactivation of RMI2 in chicken DT40 cells results in an increased level of sister chromatid exchange (SCE)--the hallmark feature of Bloom syndrome cells. Epistasis analysis revealed that RMI2 and BLM suppress SCE within the same pathway. A point mutation in the OB domain of RMI2 disrupts the association between BLM and the rest of the complex, and abrogates the ability of RMI2 to suppress elevated SCE. Our data suggest that multi-OB-fold complexes mediate two modes of BLM action: via RPA-mediated protein-DNA interaction, and via RMI-mediated protein-protein interactions.

  11. Bloom syndrome in two siblings.

    Science.gov (United States)

    Sultan, Sheikh Javeed; Sultan, Sheikh Tariq

    2010-01-01

    Bloom syndrome (congenital telangiectatic erythema) is a rare autosomal recessive disorder characterized by telangiectasias and photosensitivity, growth deficiency of prenatal onset, variable degrees of immunodeficiency, and increased susceptibility to neoplasms of many sites and types. We are reporting Bloom syndrome in two brothers from Kashmir (India), 8 and 6 years of age, who presented with erythematous rashes on the face, photosensitivity, and growth retardation.

  12. The Bloom syndrome protein limits the lethality associated with RAD51 deficiency.

    Science.gov (United States)

    Lahkim Bennani-Belhaj, Kenza; Rouzeau, Sébastien; Buhagiar-Labarchède, Géraldine; Chabosseau, Pauline; Onclercq-Delic, Rosine; Bayart, Emilie; Cordelières, Fabrice; Couturier, Jérôme; Amor-Guéret, Mounira

    2010-03-01

    Little is known about the functional interaction between the Bloom's syndrome protein (BLM) and the recombinase RAD51 within cells. Using RNA interference technology, we provide the first demonstration that RAD51 acts upstream from BLM to prevent anaphase bridge formation. RAD51 downregulation was associated with an increase in the frequency of BLM-positive anaphase bridges, but not of BLM-associated ultrafine bridges. Time-lapse live microscopy analysis of anaphase bridge cells revealed that BLM promoted cell survival in the absence of Rad51. Our results directly implicate BLM in limiting the lethality associated with RAD51 deficiency through the processing of anaphase bridges resulting from the RAD51 defect. These findings provide insight into the molecular basis of some cancers possibly associated with variants of the RAD51 gene family.

  13. Solution structure of the RecQ C-terminal domain of human Bloom syndrome protein.

    Science.gov (United States)

    Park, Chin-Ju; Ko, Junsang; Ryu, Kyoung-Seok; Choi, Byong-Seok

    2014-02-01

    RecQ C-terminal (RQC) domain is known as the main DNA binding module of RecQ helicases such as Bloom syndrome protein (BLM) and Werner syndrome protein (WRN) that recognizes various DNA structures. Even though BLM is able to resolve various DNA structures similarly to WRN, BLM has different binding preferences for DNA substrates from WRN. In this study, we determined the solution structure of the RQC domain of human BLM. The structure shares the common winged-helix motif with other RQC domains. However, half of the N-terminal has unstructured regions (α1-α2 loop and α3 region), and the aromatic side chain on the top of the β-hairpin, which is important for DNA duplex strand separation in other RQC domains, is substituted with a negatively charged residue (D1165) followed by the polar residue (Q1166). The structurally distinctive features of the RQC domain of human BLM suggest that the DNA binding modes of the BLM RQC domain may be different from those of other RQC domains.

  14. Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair.

    Science.gov (United States)

    Wan, Li; Han, Jinhua; Liu, Ting; Dong, Shunli; Xie, Feng; Chen, Hongxia; Huang, Jun

    2013-06-25

    The Bloom syndrome gene product, BLM, is a member of the highly conserved RecQ family. An emerging concept is the BLM helicase collaborates with the homologous recombination (HR) machinery to help avoid undesirable HR events and to achieve a high degree of fidelity during the HR reaction. However, exactly how such coordination occurs in vivo is poorly understood. Here, we identified a protein termed SPIDR (scaffolding protein involved in DNA repair) as the link between BLM and the HR machinery. SPIDR independently interacts with BLM and RAD51 and promotes the formation of a BLM/RAD51-containing complex of biological importance. Consistent with its role as a scaffolding protein for the assembly of BLM and RAD51 foci, cells depleted of SPIDR show increased rate of sister chromatid exchange and defects in HR. Moreover, SPIDR depletion leads to genome instability and causes hypersensitivity to DNA damaging agents. We propose that, through providing a scaffold for the cooperation of BLM and RAD51 in a multifunctional DNA-processing complex, SPIDR not only regulates the efficiency of HR, but also dictates the specific HR pathway.

  15. Transcriptomic and Protein Expression Analysis Reveals Clinicopathological Significance of Bloom Syndrome Helicase (BLM) in Breast Cancer.

    Science.gov (United States)

    Arora, Arvind; Abdel-Fatah, Tarek M A; Agarwal, Devika; Doherty, Rachel; Moseley, Paul M; Aleskandarany, Mohammed A; Green, Andrew R; Ball, Graham; Alshareeda, Alaa T; Rakha, Emad A; Chan, Stephen Y T; Ellis, Ian O; Madhusudan, Srinivasan

    2015-04-01

    Bloom syndrome helicase (BLM) has key roles in homologous recombination repair, telomere maintenance, and DNA replication. Germ-line mutations in the BLM gene causes Bloom syndrome, a rare disorder characterized by premature aging and predisposition to multiple cancers, including breast cancer. The clinicopathologic significance of BLM in sporadic breast cancers is unknown. We investigated BLM mRNA expression in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n = 1,950) and validated in an external dataset of 2,413 tumors. BLM protein level was evaluated in the Nottingham Tenovus series comprising 1,650 breast tumors. BLM mRNA overexpression was significantly associated with high histologic grade, larger tumor size, estrogen receptor-negative (ER(-)), progesterone receptor-negative (PR(-)), and triple-negative phenotypes (ps < 0.0001). BLM mRNA overexpression was also linked to aggressive molecular phenotypes, including PAM50.Her2 (P < 0.0001), PAM50.Basal (P < 0.0001), and PAM50.LumB (P < 0.0001) and Genufu subtype (ER(+)/Her2(-)/high proliferation; P < 0.0001). PAM50.LumA tumors and Genufu subtype (ER(+)/Her2(-)/low proliferation) were more likely to express low levels of BLM mRNA (ps < 0.0001). Integrative molecular clusters (intClust) intClust.1 (P < 0.0001), intClust.5 (P < 0.0001), intClust.9 (P < 0.0001), and intClust.10 (P < 0.0001) were also more likely in tumors with high BLM mRNA expression. BLM mRNA overexpression was associated with poor breast cancer-specific survival (BCSS; ps < 0.000001). At the protein level, altered subcellular localization with high cytoplasmic BLM and low nuclear BLM was linked to aggressive phenotypes. In multivariate analysis, BLM mRNA and BLM protein levels independently influenced BCSS. This is the first and the largest study to provide evidence that BLM is a promising biomarker in breast cancer.

  16. Structure and function of the regulatory HRDC domain from human Bloom syndrome protein.

    Science.gov (United States)

    Kim, Young Mee; Choi, Byong-Seok

    2010-11-01

    The helicase and RNaseD C-terminal (HRDC) domain, conserved among members of the RecQ helicase family, regulates helicase activity by virtue of variations in its surface residues. The HRDC domain of Bloom syndrome protein (BLM) is known as a critical determinant of the dissolution function of double Holliday junctions by the BLM-Topoisomerase IIIα complex. In this study, we determined the solution structure of the human BLM HRDC domain and characterized its DNA-binding activity. The BLM HRDC domain consists of five α-helices with a hydrophobic 3(10)-helical loop between helices 1 and 2 and an extended acidic surface comprising residues in helices 3-5. The BLM HRDC domain preferentially binds to ssDNA, though with a markedly low binding affinity (K(d) ∼100 μM). NMR chemical shift perturbation studies suggested that the critical DNA-binding residues of the BLM HRDC domain are located in the hydrophobic loop and the N-terminus of helix 2. Interestingly, the isolated BLM HRDC domain had quite different DNA-binding modes between ssDNA and Holliday junctions in electrophoretic mobility shift assay experiments. Based on its surface charge separation and DNA-binding properties, we suggest that the HRDC domain of BLM may be adapted for a unique function among RecQ helicases--that of bridging protein and DNA interactions.

  17. Bloom syndrome with lung involvement.

    Science.gov (United States)

    Nair, Girija; Lobo, Ivona; Jayalaksmi, T K; Uppe, Abhay; Jindal, Savita; Chandra, Abhishek; Swami, Shivani

    2009-07-01

    We report a case of a 24-year old male presented with cough and breathlessness with diabetes mellitus and diagnosed as a case of bloom syndrome. He was a product of consanguineous marriage, having short stature, dolicocephaly, polydactyly, prominent nose with telangiectasia face. The respiratory system examination revealed bilateral coarse crepitations and wheezes and the chest X-ray revealed emphysema with right middle zone inhomogenous opacity. Also, CT thorax examination revealed bilateral cystic bronchiectasis with bronchiolitis obliterans. Bloom's syndrome was diagnosed on the basis of clinical features.

  18. Defining the molecular interface that connects the Fanconi anemia protein FANCM to the Bloom syndrome dissolvasome.

    Science.gov (United States)

    Hoadley, Kelly A; Xue, Yutong; Ling, Chen; Takata, Minoru; Wang, Weidong; Keck, James L

    2012-03-20

    The RMI subcomplex (RMI1/RMI2) functions with the BLM helicase and topoisomerase IIIα in a complex called the "dissolvasome," which separates double-Holliday junction DNA structures that can arise during DNA repair. This activity suppresses potentially harmful sister chromatid exchange (SCE) events in wild-type cells but not in cells derived from Bloom syndrome patients with inactivating BLM mutations. The RMI subcomplex also associates with FANCM, a component of the Fanconi anemia (FA) core complex that is important for repair of stalled DNA replication forks. The RMI/FANCM interface appears to help coordinate dissolvasome and FA core complex activities, but its precise role remains poorly understood. Here, we define the structure of the RMI/FANCM interface and investigate its roles in coordinating cellular DNA-repair activities. The X-ray crystal structure of the RMI core complex bound to a well-conserved peptide from FANCM shows that FANCM binds to both RMI proteins through a hydrophobic "knobs-into-holes" packing arrangement. The RMI/FANCM interface is shown to be critical for interaction between the components of the dissolvasome and the FA core complex. FANCM variants that substitute alanine for key interface residues strongly destabilize the complex in solution and lead to increased SCE levels in cells that are similar to those observed in blm- or fancm-deficient cells. This study provides a molecular view of the RMI/FANCM complex and highlights a key interface utilized in coordinating the activities of two critical eukaryotic DNA-damage repair machines.

  19. Competition between the DNA unwinding and strand pairing activities of the Werner and Bloom syndrome proteins

    Directory of Open Access Journals (Sweden)

    Orren David K

    2006-01-01

    Full Text Available Abstract Background The premature aging and cancer-prone Werner and Bloom syndromes are caused by defects in the RecQ helicase enzymes WRN and BLM, respectively. Recently, both WRN and BLM (as well as several other RecQ members have been shown to possess a strand annealing activity in addition to the requisite DNA unwinding activity. Since an annealing function would appear to directly oppose the action of a helicase, we have examined in this study the dynamic equilibrium between unwinding and annealing mediated by either WRN or BLM. Results Our investigation into the competition between annealing and unwinding demonstrates that, under standard reaction conditions, WRN- or BLM-mediated annealing can partially or completely mask unwinding as measured in standard helicase assays. Several strategies were employed to suppress the annealing activity so that the actual strength of WRN- or BLM-dependent unwinding could be more accurately assessed. Interestingly, if a DNA oligomer complementary to one strand of the DNA substrate to be unwound is added during the helicase reaction, both WRN and BLM unwinding is enhanced, presumably by preventing protein-mediated re-annealing. This strategy allowed measurement of WRN-catalyzed unwinding of long (80 base pair duplex regions and fully complementary, blunt-ended duplexes, both of which were otherwise quite refractory to the helicase activity of WRN. Similarly, the addition of trap strand stimulated the ability of BLM to unwind long and blunt-ended duplexes. The stimulatory effect of the human replication protein A (hRPA, the eukaryotic single-stranded DNA binding protein on both WRN- and BLM-dependent unwinding was also re-examined in light of its possible role in preventing re-annealing. Our results show that hRPA influences the outcome of WRN and BLM helicase assays by both inhibiting re-annealing and directly promoting unwinding, with the larger contribution from the latter mechanism. Conclusion These

  20. Competition between the DNA unwinding and strand pairing activities of the Werner and Bloom syndrome proteins.

    Science.gov (United States)

    Machwe, Amrita; Lozada, Enerlyn M; Xiao, Liren; Orren, David K

    2006-01-13

    The premature aging and cancer-prone Werner and Bloom syndromes are caused by defects in the RecQ helicase enzymes WRN and BLM, respectively. Recently, both WRN and BLM (as well as several other RecQ members) have been shown to possess a strand annealing activity in addition to the requisite DNA unwinding activity. Since an annealing function would appear to directly oppose the action of a helicase, we have examined in this study the dynamic equilibrium between unwinding and annealing mediated by either WRN or BLM. Our investigation into the competition between annealing and unwinding demonstrates that, under standard reaction conditions, WRN- or BLM-mediated annealing can partially or completely mask unwinding as measured in standard helicase assays. Several strategies were employed to suppress the annealing activity so that the actual strength of WRN- or BLM-dependent unwinding could be more accurately assessed. Interestingly, if a DNA oligomer complementary to one strand of the DNA substrate to be unwound is added during the helicase reaction, both WRN and BLM unwinding is enhanced, presumably by preventing protein-mediated re-annealing. This strategy allowed measurement of WRN-catalyzed unwinding of long (80 base pair) duplex regions and fully complementary, blunt-ended duplexes, both of which were otherwise quite refractory to the helicase activity of WRN. Similarly, the addition of trap strand stimulated the ability of BLM to unwind long and blunt-ended duplexes. The stimulatory effect of the human replication protein A (hRPA, the eukaryotic single-stranded DNA binding protein) on both WRN- and BLM-dependent unwinding was also re-examined in light of its possible role in preventing re-annealing. Our results show that hRPA influences the outcome of WRN and BLM helicase assays by both inhibiting re-annealing and directly promoting unwinding, with the larger contribution from the latter mechanism. These findings indicate that measurements of unwinding by WRN

  1. Genetics Home Reference: Bloom syndrome

    Science.gov (United States)

    ... are of Central and Eastern European (Ashkenazi) Jewish background. Related Information What information about a genetic condition can statistics ... Genetic Testing Registry: Bloom syndrome Other Diagnosis and Management Resources (2 ... Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy ...

  2. Bloom syndrome with lung involvement

    Directory of Open Access Journals (Sweden)

    Nair Girija

    2009-01-01

    Full Text Available We report a case of a 24-year old male presented with cough and breathlessness with diabetes mellitus and diagnosed as a case of bloom syndrome. He was a product of consanguineous marriage, having short stature, dolicocephaly, polydactyly, prominent nose with telangiectasia face. The respiratory system examination revealed bilateral coarse crepitations and wheezes and the chest X-ray revealed emphysema with right middle zone inhomogenous opacity. Also, CT thorax examination revealed bilateral cystic bronchiectasis with bronchiolitis obliterans. Bloom′s syndrome was diagnosed on the basis of clinical features.

  3. Structural and functional analyses of disease-causing missense mutations in Bloom syndrome protein.

    Science.gov (United States)

    Guo, Rong-Bing; Rigolet, Pascal; Ren, Hua; Zhang, Bo; Zhang, Xing-Dong; Dou, Shuo-Xing; Wang, Peng-Ye; Amor-Gueret, Mounira; Xi, Xu Guang

    2007-01-01

    Bloom syndrome (BS) is an autosomal recessive disorder characterized by genomic instability and the early development of many types of cancer. Missense mutations have been identified in the BLM gene (encoding a RecQ helicase) in affected individuals, but the molecular mechanism and the structural basis of the effects of these mutations remain to be elucidated. We analysed five disease-causing missense mutations that are localized in the BLM helicase core region: Q672R, I841T, C878R, G891E and C901Y. The disease-causing mutants had low ATPase and helicase activities but their ATP binding abilities were normal, except for Q672, whose ATP binding activity was lower than that of the intact BLM helicase. Mutants C878R, mapping near motif IV, and G891E and C901Y, mapping in motif IV, displayed severe DNA-binding defects. We used molecular modelling to analyse these mutations. Our work provides insights into the molecular basis of BLM pathology, and reveals structural elements implicated in coupling DNA binding to ATP hydrolysis and DNA unwinding. Our findings will help to explain the mechanism underlying BLM catalysis and interpreting new BLM causing mutations identified in the future.

  4. Bloom syndrome helicase in meiosis: Pro-crossover functions of an anti-crossover protein.

    Science.gov (United States)

    Hatkevich, Talia; Sekelsky, Jeff

    2017-09-01

    The functions of the Bloom syndrome helicase (BLM) and its orthologs are well characterized in mitotic DNA damage repair, but their roles within the context of meiotic recombination are less clear. In meiotic recombination, multiple repair pathways are used to repair meiotic DSBs, and current studies suggest that BLM may regulate the use of these pathways. Based on literature from Saccharomyces cerevisiae, Arabidopsis thaliana, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans, we present a unified model for a critical meiotic role of BLM and its orthologs. In this model, BLM and its orthologs utilize helicase activity to regulate the use of various pathways in meiotic recombination by continuously disassembling recombination intermediates. This unwinding activity provides the meiotic program with a steady pool of early recombination substrates, increasing the probability for a DSB to be processed by the appropriate pathway. As a result of BLM activity, crossovers are properly placed throughout the genome, promoting proper chromosomal disjunction at the end of meiosis. This unified model can be used to further refine the complex role of BLM and its orthologs in meiotic recombination. © 2017 WILEY Periodicals, Inc.

  5. FE65 regulates and interacts with the Bloom syndrome protein in dynamic nuclear spheres - potential relevance to Alzheimer's disease.

    Science.gov (United States)

    Schrötter, Andreas; Mastalski, Thomas; Nensa, Fabian M; Neumann, Martin; Loosse, Christina; Pfeiffer, Kathy; Magraoui, Fouzi El; Platta, Harald W; Erdmann, Ralf; Theiss, Carsten; Uszkoreit, Julian; Eisenacher, Martin; Meyer, Helmut E; Marcus, Katrin; Müller, Thorsten

    2013-06-01

    The intracellular domain of the amyloid precursor protein (AICD) is generated following cleavage of the precursor by the γ-secretase complex and is involved in membrane to nucleus signaling, for which the binding of AICD to the adapter protein FE65 is essential. Here we show that FE65 knockdown causes a downregulation of the protein Bloom syndrome protein (BLM) and the minichromosome maintenance (MCM) protein family and that elevated nuclear levels of FE65 result in stabilization of the BLM protein in nuclear mobile spheres. These spheres are able to grow and fuse, and potentially correspond to the nuclear domain 10. BLM plays a role in DNA replication and repair mechanisms and FE65 was also shown to play a role in DNA damage response in the cell. A set of proliferation assays in our work revealed that FE65 knockdown in HEK293T cells reduced cell replication. On the basis of these results, we hypothesize that nuclear FE65 levels (nuclear FE65/BLM containing spheres) may regulate cell cycle re-entry in neurons as a result of increased interaction of FE65 with BLM and/or an increase in MCM protein levels. Thus, FE65 interactions with BLM and MCM proteins may contribute to the neuronal cell cycle re-entry observed in brains affected by Alzheimer's disease.

  6. Bloom syndrome in an Indian child.

    Science.gov (United States)

    Inamadar, Arun C; Palit, Aparna

    2005-01-01

    A girl presented with severely stunted growth, photosensitivity, and a characteristic facies. Cytogenetic studies were suggestive of Bloom syndrome. This disorder has not been previously documented in the literature in an Indian child. Minor variations in characteristics in this patient have been highlighted. Cytogenetically, she was found to be a low sister chromatid exchange mosaicism of Bloom syndrome.

  7. Protein kinase A subunit expression is altered in Bloom syndrome fibroblasts and the BLM protein is increased in adrenocortical hyperplasias: inverse findings for BLM and PRKAR1A.

    Science.gov (United States)

    Heyerdahl, S L; Boikos, S; Horvath, A; Giatzakis, C; Bossis, I; Stratakis, C A

    2008-06-01

    Bloom syndrome is a genetic disorder associated with chromosomal instability and a predisposition to tumors that is caused by germline mutations of the BLM gene, a RecQ helicase. Benign adrenocortical tumors display a degree of chromosomal instability that is more significant than benign tumors of other tissues. Cortisol-producing hyperplasias, such as primary pigmented nodular adrenocortical disease (PPNAD), which has been associated with protein kinase A (PKA) abnormalities and/or PRKAR1A mutations, also show genomic instability. Another RecQ helicase, WRN, directly interacts with the PRKAR1B subunit of PKA. In this study, we have investigated the PRKAR1A expression in primary human Bloom syndrome cell lines with known BLM mutations and examined the BLM gene expression in PPNAD and other adrenal tumor tissues. PRKAR1A and other protein kinase A (PKA) subunits were expressed in Bloom syndrome cells and their level of expression differed by subunit and cell type. Overall, fibroblasts exhibited a significant decrease in protein expression of all PKA subunits except for PRKAR1A, a pattern that has been associated with neoplastic transformation in several cell types. The BLM protein was upregulated in PPNAD and other hyperplasias, compared to samples from normal adrenals and normal cortex, as well as samples from cortisol- and aldosterone-producing adenomas (in which BLM was largely absent). These data reveal an inverse relationship between BLM and PRKAR1A: BLM deficiency is associated with a relative excess of PRKAR1A in fibroblasts compared to other PKA subunits; and PRKAR1A deficiency is associated with increased BLM protein in adrenal hyperplasias.

  8. The Werner and Bloom syndrome proteins help resolve replication blockage by converting (regressed) holliday junctions to functional replication forks.

    Science.gov (United States)

    Machwe, Amrita; Karale, Rajashree; Xu, Xioahua; Liu, Yilun; Orren, David K

    2011-08-16

    Cells cope with blockage of replication fork progression in a manner that allows DNA synthesis to be completed and genomic instability minimized. Models for resolution of blocked replication involve fork regression to form Holliday junction structures. The human RecQ helicases WRN and BLM (deficient in Werner and Bloom syndromes, respectively) are critical for maintaining genomic stability and thought to function in accurate resolution of replication blockage. Consistent with this notion, WRN and BLM localize to sites of blocked replication after certain DNA-damaging treatments and exhibit enhanced activity on replication and recombination intermediates. Here we examine the actions of WRN and BLM on a special Holliday junction substrate reflective of a regressed replication fork. Our results demonstrate that, in reactions requiring ATP hydrolysis, both WRN and BLM convert this Holliday junction substrate primarily to a four-stranded replication fork structure, suggesting they target the Holliday junction to initiate branch migration. In agreement, the Holliday junction binding protein RuvA inhibits the WRN- and BLM-mediated conversion reactions. Importantly, this conversion product is suitable for replication with its leading daughter strand readily extended by DNA polymerases. Furthermore, binding to and conversion of this Holliday junction are optimal at low MgCl(2) concentrations, suggesting that WRN and BLM preferentially act on the square planar (open) conformation of Holliday junctions. Our findings suggest that, subsequent to fork regression events, WRN and/or BLM could re-establish functional replication forks to help overcome fork blockage. Such a function is highly consistent with phenotypes associated with WRN- and BLM-deficient cells.

  9. Clinical features of Bloom syndrome and function of the causative gene, BLM helicase.

    Science.gov (United States)

    Kaneko, Hideo; Kondo, Naomi

    2004-05-01

    Bloom syndrome is a rare autosomal recessive genetic disorder characterized by growth deficiency, unusual facies, sun-sensitive telangiectatic erythema, immunodeficiency and predisposition to cancer. The causative gene for Bloom syndrome is BLM, which encodes the BLM RecQ helicase homolog protein. The first part of this review describes a long-term follow-up study of two Bloom syndrome siblings. Subsequently, the focus is placed on the functional domains of BLM. Laboratory diagnosis of Bloom syndrome by detecting mutations in BLM is laborious and impractical, unless there are common mutations in a population. Immunoblot and immunohistochemical analyses for the detection of the BLM protein using a polyclonal BLM antibody, which are useful approaches for clinical diagnosis of Bloom syndrome, are also described. In addition, a useful adjunct for the diagnosis of Bloom syndrome in terms of the BLM function is investigated, since disease cells must have the defective BLM helicase function. This review also discusses the nuclear localization signal of BLM, the proteins that interact with BLM and tumors originating from Bloom syndrome.

  10. Bloom syndrome: multiple retinopathies in a chromosome breakage disorder.

    Science.gov (United States)

    Bhisitkul, R B; Rizen, M

    2004-03-01

    To describe multiple retinal abnormalities in a patient with Bloom syndrome, including early macular drusen, diabetic retinopathy, and the onset of leukaemic retinopathy. Clinical data were collected over 1 year of follow up, and ocular abnormalities in Bloom syndrome were reviewed from the literature. A 39 year old man with a rare autosomal recessive "chromosome breakage" syndrome was followed. A variety of ocular findings have been reported in Bloom syndrome; this patient had hard drusen in both maculae, non-proliferative diabetic retinopathy, and haemorrhagic retinopathy as a herald of acute lymphocytic leukaemia. Bloom syndrome is a rare disorder of genomic instability, in which a variety of ocular abnormalities have been found. Described here are multiple retinal manifestations arising from characteristic systemic associations of diabetes mellitus and leukaemia, as well as macular hard drusen.

  11. Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes.

    Science.gov (United States)

    Du, Xiaobing; Shen, Johnny; Kugan, Nishan; Furth, Emma E; Lombard, David B; Cheung, Catherine; Pak, Sally; Luo, Guangbin; Pignolo, Robert J; DePinho, Ronald A; Guarente, Leonard; Johnson, F Brad

    2004-10-01

    The Werner and Bloom syndromes are caused by loss-of-function mutations in WRN and BLM, respectively, which encode the RecQ family DNA helicases WRN and BLM, respectively. Persons with Werner syndrome displays premature aging of the skin, vasculature, reproductive system, and bone, and those with Bloom syndrome display more limited features of aging, including premature menopause; both syndromes involve genome instability and increased cancer. The proteins participate in recombinational repair of stalled replication forks or DNA breaks, but the precise functions of the proteins that prevent rapid aging are unknown. Accumulating evidence points to telomeres as targets of WRN and BLM, but the importance in vivo of the proteins in telomere biology has not been tested. We show that Wrn and Blm mutations each accentuate pathology in later-generation mice lacking the telomerase RNA template Terc, including acceleration of phenotypes characteristic of latest-generation Terc mutants. Furthermore, pathology not observed in Terc mutants but similar to that observed in Werner syndrome and Bloom syndrome, such as bone loss, was observed. The pathology was accompanied by enhanced telomere dysfunction, including end-to-end chromosome fusions and greater loss of telomere repeat DNA compared with Terc mutants. These findings indicate that telomere dysfunction may contribute to the pathogenesis of Werner syndrome and Bloom syndrome.

  12. Bloom syndrome in short children born small for gestational age: a challenging diagnosis.

    Science.gov (United States)

    Renes, Judith S; Willemsen, Ruben H; Wagner, Anja; Finken, Martijn J J; Hokken-Koelega, Anita C S

    2013-10-01

    GH treatment has become a frequently applied growth-promoting therapy in short children born small for gestational age (SGA). In some disorders GH treatment is contraindicated, eg, chromosomal breakage syndromes. Bloom syndrome is a rare chromosomal breakage syndrome characterized by severe pre- and postnatal growth deficiency, a photosensitive facial erythema, immunodeficiency, mental retardation or learning disabilities, endocrinopathies, and a predisposition to develop a wide variety of cancers. We report 2 patients with Bloom syndrome illustrating the variety in clinical manifestations. They were initially diagnosed with short stature after SGA birth and Silver Russell syndrome and treated with GH. Both patients presented with pre- and postnatal growth failure but no clear other characteristic features associated with Bloom syndrome. Photosensitive skin lesions developed only at a pubertal age and were minimal. Also, both children showed normal immunoglobulin levels, normal development, and no signs of endocrinopathies at start of GH. Dysmorphic features resembling Silver Russell syndrome were observed in both patients. Remarkably, during GH treatment IGF-1 levels increased to values greater than 3.5 SD score, with normal IGF binding protein-3 levels. Short children born SGA comprise a heterogeneous group. Bloom syndrome should be tested for in children with consanguineous parents, dysmorphic features (particularly resembling Silver Russell syndrome), skin abnormalities, and/or IGF-1 levels greater than 2.5 SD score during standard GH treatment with normal IGF binding protein-3 levels.

  13. Burkitt lymphoma in a child with Bloom syndrome.

    Science.gov (United States)

    Fedhila-Ben Ayed, F; Douira-Khomsi, W; Rhayem, S; Jelassi, M; Zribi, H; Chaabouni, M; Khemiri, M; Bellagha, I; Barsaoui, S

    2016-04-01

    Bloom syndrome is a rare disease characterized by chromosomal instability and increased risk of developing lymphoma. We report on a case of Bloom syndrome in a 5-year-old boy with Burkitt lymphoma. The diagnosis was suspected by growth retardation, repeated respiratory infections, facial telangiectasia, and a low immunoglobulin level, then confirmed cytogenetically by sister chromatid exchanges. Chemotherapy was poorly tolerated, which required reducing the doses. Unfortunately, it was not sufficient to control the neoplasm and the patient died 14 months after diagnosis. Cancers in Bloom syndrome are a challenge since the potentially life-threatening side effects of the chemotherapy may require modifications in standard treatment such as dose reduction, which can compromise the tumor prognosis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Functional deficiency of fibroblasts heterozygous for Bloom syndrome as specific manifestation of the primary defect.

    OpenAIRE

    Bartram, C.R.; Rüdiger, H W; Schmidt-Preuss, U; Passarge, E

    1981-01-01

    The effect on the rate of sister chromatid exchanges (SCEs) in Bloom syndrome fibroblasts by cocultivation with Fanconi anemia and xeroderma pigmentosum fibroblasts and with Bloom syndrome heterozygotes was studied. Cells of Fanconi anemia and xeroderma origin reduced the rate of SCEs in Bloom cells by about 45%-50%, just as control cells do. In contrast, heterozygous Bloom cells reduced the rate of SCEs by only 16%-28%. In absolute figures, Fanconi cells reduced the mean rate of SCE in Bloom...

  15. Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome.

    Science.gov (United States)

    Hudson, Damien F; Amor, David J; Boys, Amber; Butler, Kathy; Williams, Lorna; Zhang, Tao; Kalitsis, Paul

    2016-12-01

    Bloom syndrome is a recessive human genetic disorder with features of genome instability, growth deficiency and predisposition to cancer. The only known causative gene is the BLM helicase that is a member of a protein complex along with topoisomerase III alpha, RMI1 and 2, which maintains replication fork stability and dissolves double Holliday junctions to prevent genome instability. Here we report the identification of a second gene, RMI2, that is deleted in affected siblings with Bloom-like features. Cells from homozygous individuals exhibit elevated rates of sister chromatid exchange, anaphase DNA bridges and micronuclei. Similar genome and chromosome instability phenotypes are observed in independently derived RMI2 knockout cells. In both patient and knockout cell lines reduced localisation of BLM to ultra fine DNA bridges and FANCD2 at foci linking bridges are observed. Overall, loss of RMI2 produces a partially active BLM complex with mild features of Bloom syndrome.

  16. A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.

    NARCIS (Netherlands)

    Meetei, AR; Sechi, S; Wallisch, M; Yang, D; Young, MK; Joenje, H.; Hoatlin, M.E.

    2003-01-01

    Bloom syndrome (BS) is a genetic disorder associated with dwarfism, immunodeficiency, reduced fertility, and an elevated risk of cancer. To investigate the mechanism of this disease, we isolated from human HeLa extracts three complexes containing the helicase defective in BS, BLM. Interestingly, one

  17. A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.

    NARCIS (Netherlands)

    Meetei, AR; Sechi, S; Wallisch, M; Yang, D; Young, MK; Joenje, H.; Hoatlin, M.E.

    2003-01-01

    Bloom syndrome (BS) is a genetic disorder associated with dwarfism, immunodeficiency, reduced fertility, and an elevated risk of cancer. To investigate the mechanism of this disease, we isolated from human HeLa extracts three complexes containing the helicase defective in BS, BLM. Interestingly, one

  18. Augmented cell death with Bloom syndrome helicase deficiency.

    Science.gov (United States)

    Kaneko, Hideo; Fukao, Toshiyuki; Kasahara, Kimiko; Yamada, Taketo; Kondo, Naomi

    2011-01-01

    Bloom syndrome (BS) is a rare autosomal genetic disorder characterized by lupus-like erythematous telangi-ectasias of the face, sun sensitivity, infertility, stunted growth, upper respiratory infection, and gastrointestinal infections commonly associated with decreased immuno-globulin levels. The syndrome is associated with immuno-deficiency of a generalized type, ranging from mild and essentially asympto-matic to severe. Chromosomal abnormalities are hallmarks of the disorder, and high frequencies of sister chromatid exchanges and quadriradial configurations in lymphocytes and fibroblasts are diagnostic features. BS is caused by mutations in BLM, a member of the RecQ helicase family. We determined whether BLM deficiency has any effects on cell growth and death in BLM-deficient cells and mice. BLM-deficient EB-virus-transformed cell lines from BS patients and embryonic fibroblasts from BLM-/- mice showed slower growth than wild-type cells. BLM-deficient cells showed abnormal p53 protein expression after irradiation. In BLM-/- mice, small body size, reduced number of fetal liver cells and increased cell death were observed. BLM deficiency causes the up-regulation of p53, double-strand break and apoptosis, which are likely observed in irradiated control cells. Slow cell growth and increased cell death may be one of the causes of the small body size associated with BS patients.

  19. FANCM: A Landing Pad for the Fanconi Anemia and Bloom's Syndrome Complexes

    OpenAIRE

    Vinciguerra, Patrizia; D'Andrea, Alan D.

    2009-01-01

    Here, Deans and West (2009) reveal the molecular basis of the phenotypic similarities between Fanconi Anemia (FA) and Bloom's Syndrome, identifying FANCM as the anchor for both FA and Bloom's complexes at the site of the DNA interstrand crosslink.

  20. Deficiency of Bloom syndrome helicase activity is radiomimetic.

    Science.gov (United States)

    Horowitz, David P; Topaloglu, Ozlem; Zhang, Yonggang; Bunz, Fred

    2008-11-01

    Bloom syndrome is caused by homozygous mutations in BLM, which encodes a RecQ DNA helicase. Patient-derived cells deficient in BLM helicase activity exhibit genetic instability--apparent cytogenetically as sister chromatid exchanges--and activated DNA damage signaling. In this report, we show that BLM-knockout colorectal cancer cells exhibited endogenous, ATM-dependent double-strand DNA break responses similar to those recently observed in Bloom syndrome patient-derived cells. Xenograft tumors established from BLM-deficient cancer cells were not radiosensitive, but exhibited growth impairment that was comparable to that of wild type tumors treated with a single, high dose of ionizing radiation. These results suggest that pharmacological inhibitors of BLM would have a radiomimetic effect and that transient inhibition of BLM activity might be a viable strategy for anticancer therapy.

  1. Cellular defects caused by hypomorphic variants of the Bloom syndrome helicase gene BLM.

    Science.gov (United States)

    Shastri, Vivek M; Schmidt, Kristina H

    2016-01-01

    Bloom syndrome is an autosomal recessive disorder characterized by extraordinary cancer incidence early in life and an average life expectancy of ~27 years. Premature stop codons in BLM, which encodes a DNA helicase that functions in DNA double-strand-break repair, make up the vast majority of Bloom syndrome mutations, with only 13 single amino acid changes identified in the syndrome. Sequencing projects have identified nearly one hundred single nucleotide variants in BLM that cause amino acid changes of uncertain significance. Here, in addition to identifying five BLM variants incapable of complementing certain defects of Bloom syndrome cells, making them candidates for new Bloom syndrome causing mutations, we characterize a new class of BLM variants that cause some, but not all, cellular defects of Bloom syndrome. We find elevated sister-chromatid exchanges, a delayed DNA damage response and inefficient DNA repair. Conversely, hydroxyurea sensitivity and quadriradial chromosome accumulation, both characteristic of Bloom syndrome cells, are absent. These intermediate variants affect sites in BLM that function in ATP hydrolysis and in contacting double-stranded DNA. Allele frequency and cellular defects suggest candidates for new Bloom syndrome causing mutations, and intermediate BLM variants that are hypomorphic which, instead of causing Bloom syndrome, may increase a person's risk for cancer or possibly other Bloom-syndrome-associated disorders, such as type-2 diabetes.

  2. Proton beam therapy for malignancy in Bloom syndrome.

    Science.gov (United States)

    Mizumoto, M; Hashii, H; Senarita, M; Sakai, S; Wada, T; Okumura, T; Tsuboi, K; Sakurai, H

    2013-04-01

    Bloom syndrome is a DNA repair disorder that is hypersensitive to radiotherapy. We describe the first case in which proton beam therapy (PBT) was used in a patient with Bloom syndrome to treat oropharyngeal cancer. The patient was a 32-year-old woman with Bloom syndrome who was diagnosed with oropharyngeal cancer staged as T2N2bM0 poorly differentiated squamous cell carcinoma. The primary tumor was located on the right tongue base and extended to the right lateral pharyngeal wall. Several right upper region lymph nodes were positive for metastases. We selected PBT in anticipation of dose reduction to normal tissue. The clinical target volume was defined as the area of the primary tumor and lymph node metastases plus an 8-mm margin. After treatment with 36 GyE (Gray equivalent) in 20 fractions (4-5 fractions per week), dietary intake was decreased by mucositis and intravenous hyperalimentation was started. Termination of treatment for 2.5 weeks was required to relieve mucositis. Administration of 59.4 GyE in 33 fractions markedly reduced the size of the primary tumor, but also caused moderate mucositis that required termination of PBT. One month later, lung metastases and breast cancer developed and the patient died 9 months after PBT. At this time the reduction in size of the primary tumor was maintained without severe late toxicity. We obtained almost complete response for a radiosensitive patient with a deficiency of DNA repair, indicating the excellent dose concentration of proton beam therapy.

  3. Surveillance and treatment of malignancy in Bloom syndrome.

    Science.gov (United States)

    Thomas, E R A; Shanley, S; Walker, L; Eeles, R

    2008-06-01

    We report a patient with Bloom syndrome, a rare autosomal recessive condition characterised by chromosomal instability leading to a high risk of cancer at an early age. The diagnosis should be considered in patients with any cancer of significantly early onset, short stature and a photosensitive lupus-like rash on the face. Diagnostic confirmation is obtained from chromosome studies that show significantly increased numbers of sister chromatid exchanges. There are important management implications, including minimising the use of ionising radiation in surveillance and treatment.

  4. The X chromosome: does it have a role in Bloom syndrome, a genomic instability disorder?

    Science.gov (United States)

    Aslan, Deniz

    2014-01-01

    The Bloom syndrome, caused by mutations in a single gene [BLM (15q26.1)], is a rare genomic instability syndrome. Despite its autosomal recessive transmission, it shows a male dominance, suggesting the possibility of a subgroup with X-linked recessive inheritance. In view of the latest molecular developments achieved in the other genomic instability syndromes, the potential functions of the X chromosome in maintaining genomic stability, and particularly, the first clues of Bloom syndrome development by mechanisms other than the BLM, we suggest herein that the X chromosome should be investigated in Bloom syndrome.

  5. Lupus-like histopathology in bloom syndrome: reexamining the clinical and histologic implications of photosensitivity.

    Science.gov (United States)

    McGowan, Joseph; Maize, John; Cook, Joel

    2009-12-01

    Bloom syndrome is a rare genodermatosis of autosomal recessive inheritance. Although lupus-like skin lesions characterize this disorder, mechanisms of photosensitivity are poorly understood. In this case presentation, the authors report a patient with Bloom syndrome whose lupus-like facial rash revealed striking histopathologic similarities to cutaneous lupus erythematosus.

  6. [Bloom syndrome. Clinical manifestations and cromosomal study in a Mexican child].

    Science.gov (United States)

    Rosales-Solis, Gloria María; Martínez-Longoria, César Adrián; Guerrero-González, Guillermo Antonio; Ocampo-Garza, Jorge; Ocampo-Candiani, Jorge

    Bloom syndrome is an extremely rare inherited disorder. We present a case of Bloom syndrome with a chromosomal study in a Mexican five-year-old patient who presented growth retardation, narrow facies with poikiloderma, café-au-lait, macules and photosensitivity.

  7. Bloom syndrome and maternal uniparental disomy for chromosome 15

    Energy Technology Data Exchange (ETDEWEB)

    Woodage, T.; Prasad, M.; Trent, R.J.; Smith, A. (Children' s Hospital, Camperdown, New South Wales (New Zealand)); Dixon, J.W.; Romain, D.R.; Columbano-Green, L.M.; Selby, R.E. (Wellington Hospital (New Zealand)); Graham, D. (Waikato Hospital, Hamilton (New Zealand)); Rogan, P.K. (Pennsylvania State Univ., Hershey, PA (United States)) (and others)

    1994-07-01

    Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions. 37 refs., 3 figs., 2 tabs.

  8. Cellular defects caused by hypomorphic variants of the Bloom syndrome helicase gene BLM

    OpenAIRE

    Shastri, Vivek M.; Schmidt, Kristina H.

    2015-01-01

    Abstract Background Bloom syndrome is an autosomal recessive disorder characterized by extraordinary cancer incidence early in life and an average life expectancy of ~27 years. Premature stop codons in BLM , which encodes a DNA helicase that functions in DNA double‐strand‐break repair, make up the vast majority of Bloom syndrome mutations, with only 13 single amino acid changes identified in the syndrome. Sequencing projects have identified nearly one hundred single nucleotide variants in BLM...

  9. Three new BLM gene mutations associated with Bloom syndrome.

    Science.gov (United States)

    Amor-Guéret, Mounira; Dubois-d'Enghien, Catherine; Laugé, Anthony; Onclercq-Delic, Rosine; Barakat, Abdelhamid; Chadli, Elbekkay; Bousfiha, Ahmed Aziz; Benjelloun, Meriem; Flori, Elisabeth; Doray, Bérénice; Laugel, Vincent; Lourenço, Maria Teresa; Gonçalves, Rui; Sousa, Silvia; Couturier, Jérôme; Stoppa-Lyonnet, Dominique

    2008-06-01

    Bloom's syndrome (BS) is a rare autosomal recessive disease predisposing patients to all types of cancers affecting the general population. BS cells display a high level of genetic instability, including a 10-fold increase in the rate of sister chromatid exchanges, currently the only objective criterion for BS diagnosis. We have developed a method for screening the BLM gene for mutations based on direct genomic DNA sequencing. A questionnaire based on clinical information, cytogenetic features, and family history was addressed to physicians prescribing BS genetic screening, with the aim of confirming or guiding diagnosis. We report here four BLM gene mutations, three of which have not been described before. Three of the mutations are frameshift mutations, and the fourth is a nonsense mutation. All these mutations introduce a stop codon, and may therefore be considered to have deleterious biological effect. This approach should make it possible to identify new mutations and to correlate them with clinical information.

  10. A case of Bloom syndrome with uncommon clinical manifestations confirmed on genetic testing.

    Science.gov (United States)

    Jian-Bing, Wu; Cheng-Rang, Li; Yi-Ping, Ma; Nan, Sheng; Hui, Li; Lin, Lin

    2016-02-01

    Bloom syndrome, a rare autosomal-recessive disorder, characteristically presents with photosensitivity, telangiectatic facial erythema, and growth deficiency. We present a case of Bloom syndrome with uncommon clinical manifestations including alopecia areata, eyebrow hair loss, flat nose, reticular pigmentation, and short sharpened distal phalanges with fingernails that were wider than they were long. We detected the Bloom syndrome gene, BLM, which is one of the members of the RecQ family of DNA helicases, and found changes in 2 heterozygous nucleotide sites in the patient as well as her father and mother.

  11. Bloom syndrome complicated by colonic cancer in a young Tunisian woman.

    Science.gov (United States)

    Benjazia, Elhem; Turki, Hajer; Atig, Amira; Khalifa, Mabrouk; Letaief, Amel; Bahri, Fethi; Braham, Ahlem

    2011-10-01

    Bloom syndrome (BS) is an autosomal recessive inherited disorder characterized by chromosomal instability leading to a high risk of cancer at an early age. The diagnosis should be considered in patients with short stature, photosensitivity, variable degrees of immunodeficiency, and hypogonadism. We report a 19-year-old woman, with history of dysmorphic features and recurrent infections. The diagnosis of bloom syndrome was made and confirmed cytogenetically at the age of 14 years. She developed a colon cancer revealed by venous thrombosis and anemia. She died after 15 days of the cancer diagnosis. This is the first registrated case of confirmed Bloom syndrome in Tunisian population.

  12. Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome.

    Science.gov (United States)

    Chabosseau, Pauline; Buhagiar-Labarchède, Géraldine; Onclercq-Delic, Rosine; Lambert, Sarah; Debatisse, Michelle; Brison, Olivier; Amor-Guéret, Mounira

    2011-06-28

    Defects in DNA replication are associated with genetic instability and cancer development, as illustrated in Bloom syndrome. Features of this syndrome include a slowdown in replication speed, defective fork reactivation and high rates of sister chromatid exchange, with a general predisposition to cancer. Bloom syndrome is caused by mutations in the BLM gene encoding a RecQ helicase. Here we report that BLM deficiency is associated with a strong cytidine deaminase defect, leading to pyrimidine pool disequilibrium. In BLM-deficient cells, pyrimidine pool normalization leads to reduction of sister chromatid exchange frequency and is sufficient for full restoration of replication fork velocity but not the fork restart defect, thus identifying the part of the Bloom syndrome phenotype because of pyrimidine pool imbalance. This study provides new insights into the molecular basis of control of replication speed and the genetic instability associated with Bloom syndrome. Nucleotide pool disequilibrium could be a general phenomenon in a large spectrum of precancerous and cancer cells.

  13. Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes

    Directory of Open Access Journals (Sweden)

    Killen Michael W

    2012-10-01

    Full Text Available Abstract Defects in the human BLM gene cause Bloom syndrome, notable for early development of tumors in a broad variety of tissues. On the basis of sequence similarity, BLM has been identified as one of the five human homologs of RecQ from Escherichia coli. Nevertheless, biochemical characterization of the BLM protein indicates far greater functional similarity to the E. coli RecG protein and there is no known RecG homolog in human cells. To explore the possibility that the shared biochemistries of BLM and RecG may represent an example of convergent evolution of cellular function where in humans BLM has evolved to fulfill the genomic stabilization role of RecG, we determined whether expression of RecG in human BLM-deficient cells could suppress established functional cellular Bloom syndrome phenotypes. We found that RecG can indeed largely suppress both the definitive elevated sister chromatid exchange phenotype and the more recently demonstrated gene cluster instability phenotype of BLM-deficient cells. In contrast, expression of RecG has no impact on either of these phenotypes in human cells with functional BLM protein. These results suggest that the combination of biochemical activities shared by RecG and BLM fill the same evolutionary niche in preserving genomic integrity without requiring exactly identical molecular mechanisms.

  14. Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes.

    Science.gov (United States)

    Killen, Michael W; Stults, Dawn M; Wilson, William A; Pierce, Andrew J

    2012-10-30

    Defects in the human BLM gene cause Bloom syndrome, notable for early development of tumors in a broad variety of tissues. On the basis of sequence similarity, BLM has been identified as one of the five human homologs of RecQ from Escherichia coli. Nevertheless, biochemical characterization of the BLM protein indicates far greater functional similarity to the E. coli RecG protein and there is no known RecG homolog in human cells. To explore the possibility that the shared biochemistries of BLM and RecG may represent an example of convergent evolution of cellular function where in humans BLM has evolved to fulfill the genomic stabilization role of RecG, we determined whether expression of RecG in human BLM-deficient cells could suppress established functional cellular Bloom syndrome phenotypes. We found that RecG can indeed largely suppress both the definitive elevated sister chromatid exchange phenotype and the more recently demonstrated gene cluster instability phenotype of BLM-deficient cells. In contrast, expression of RecG has no impact on either of these phenotypes in human cells with functional BLM protein. These results suggest that the combination of biochemical activities shared by RecG and BLM fill the same evolutionary niche in preserving genomic integrity without requiring exactly identical molecular mechanisms.

  15. The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability

    Directory of Open Access Journals (Sweden)

    Noonan James P

    2001-07-01

    Full Text Available Abstract Background Bloom syndrome is a rare cancer-prone disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. Bloom syndrome cells have a distinctive high frequency of sister chromatid exchange and quadriradial formation. BLM, the protein altered in BS, is a member of the RecQ DNA helicase family, whose members share an average of 40% identity in the helicase domain and have divergent N-terminal and C-terminal flanking regions of variable lengths. The BLM DNA helicase has been shown to localize to the ND10 (nuclear domain 10 or PML (promyelocytic leukemia nuclear bodies, where it associates with TOPIIIα, and to the nucleolus. Results This report demonstrates that the N-terminal domain of BLM is responsible for localization of the protein to the nuclear bodies, while the C-terminal domain directs the protein to the nucleolus. Deletions of the N-terminal domain of BLM have little effect on sister chromatid exchange frequency and chromosome stability as compared to helicase and C-terminal mutations which can increase SCE frequency and chromosome abnormalities. Conclusion The helicase activity and the C-terminal domain of BLM are critical for maintaining genomic stability as measured by the sister chromatid exchange assay. The localization of BLM into the nucleolus by the C-terminal domain appears to be more important to genomic stability than localization in the nuclear bodies.

  16. Bloom syndrome in short children born small for gestational age: A challenging diagnosis

    NARCIS (Netherlands)

    J.S. Renes (Judith); R.H. Willemsen (Ruben); A. Wagner (Anja); M.J. Finken (Martijn); A.C.S. Hokken-Koelega (Anita)

    2013-01-01

    textabstractBackground: GH treatment has become a frequently applied growth-promoting therapy in short children born small for gestational age (SGA). In some disorders GH treatment is contraindicated, eg, chromosomal breakage syndromes. Bloom syndrome is a rare chromosomal breakage syndrome characte

  17. Bloom syndrome in short children born small for gestational age: A challenging diagnosis

    NARCIS (Netherlands)

    J.S. Renes (Judith); R.H. Willemsen (Ruben); A. Wagner (Anja); M.J. Finken (Martijn); A.C.S. Hokken-Koelega (Anita)

    2013-01-01

    textabstractBackground: GH treatment has become a frequently applied growth-promoting therapy in short children born small for gestational age (SGA). In some disorders GH treatment is contraindicated, eg, chromosomal breakage syndromes. Bloom syndrome is a rare chromosomal breakage syndrome characte

  18. Removal of the bloom syndrome DNA helicase extends the utility of imprecise transposon excision for making null mutations in Drosophila.

    Science.gov (United States)

    Witsell, Alice; Kane, Daniel P; Rubin, Sarah; McVey, Mitch

    2009-11-01

    Transposable elements are frequently used in Drosophila melanogaster for imprecise excision screens to delete genes of interest. However, these screens are highly variable in the number and size of deletions that are recovered. Here, we show that conducting excision screens in mus309 mutant flies that lack DmBlm, the Drosophila ortholog of the Bloom syndrome protein, increases the percentage and overall size of flanking deletions recovered after excision of either P or Minos elements.

  19. Bloom Syndrome Helicase Promotes Meiotic Crossover Patterning and Homolog Disjunction.

    Science.gov (United States)

    Hatkevich, Talia; Kohl, Kathryn P; McMahan, Susan; Hartmann, Michaelyn A; Williams, Andrew M; Sekelsky, Jeff

    2017-01-09

    In most sexually reproducing organisms, crossover formation between homologous chromosomes is necessary for proper chromosome disjunction during meiosis I. During meiotic recombination, a subset of programmed DNA double-strand breaks (DSBs) are repaired as crossovers, with the remainder becoming noncrossovers [1]. Whether a repair intermediate is designated to become a crossover is a highly regulated decision that integrates several crossover patterning processes, both along chromosome arms (interference and the centromere effect) and between chromosomes (crossover assurance) [2]. Because the mechanisms that generate crossover patterning have remained elusive for over a century, it has been difficult to assess the relationship between crossover patterning and meiotic chromosome behavior. We show here that meiotic crossover patterning is lost in Drosophila melanogaster mutants that lack the Bloom syndrome helicase. In the absence of interference and the centromere effect, crossovers are distributed more uniformly along chromosomes. Crossovers even occur on the small chromosome 4, which normally never has meiotic crossovers [3]. Regulated distribution of crossovers between chromosome pairs is also lost, resulting in an elevated frequency of homologs that do not receive a crossover, which in turn leads to elevated nondisjunction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. 3. Chromosomal instability in B-lymphoblasotoid cell lines from Werner's and Bloom's syndrome patients

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Werner's syndrome (WS) and Bloom's syndrome (BS) are rare autosomal recessive diseases in which the feature of premature aging and the elevated risk of neoplasia may be associated with genomic instability. To cha-racterize the genomic instability of WS and BS, B-lymphoblastoid cell lines (LCLs) from WS and BS patients were cytogenetically analyzed, comparing to those from healthy donors. Although all

  1. Structure and Cellular Roles of the RMI Core Complex from the Bloom Syndrome Dissolvasome

    Energy Technology Data Exchange (ETDEWEB)

    Hoadley, Kelly A.; Xu, Dongyi; Xue, Yutong; Satyshur, Kenneth A.; Wang, Weidong; Keck, James L. (NIH); (UW-MED)

    2010-11-11

    BLM, the protein product of the gene mutated in Bloom syndrome, is one of five human RecQ helicases. It functions to separate double Holliday junction DNA without genetic exchange as a component of the dissolvasome, which also includes topoisomerase III{alpha} and the RMI (RecQ-mediated genome instability) subcomplex (RMI1 and RMI2). We describe the crystal structure of the RMI core complex, comprising RMI2 and the C-terminal OB domain of RMI1. The overall RMI core structure strongly resembles two-thirds of the trimerization core of the eukaryotic single-stranded DNA-binding protein, Replication Protein A. Immunoprecipitation experiments with RMI2 variants confirm key interactions that stabilize the RMI core interface. Disruption of this interface leads to a dramatic increase in cellular sister chromatid exchange events similar to that seen in BLM-deficient cells. The RMI core interface is therefore crucial for BLM dissolvasome assembly and may have additional cellular roles as a docking hub for other proteins.

  2. Structure and cellular roles of the RMI core complex from the bloom syndrome dissolvasome.

    Science.gov (United States)

    Hoadley, Kelly A; Xu, Dongyi; Xue, Yutong; Satyshur, Kenneth A; Wang, Weidong; Keck, James L

    2010-09-08

    BLM, the protein product of the gene mutated in Bloom syndrome, is one of five human RecQ helicases. It functions to separate double Holliday junction DNA without genetic exchange as a component of the "dissolvasome," which also includes topoisomerase IIIα and the RMI (RecQ-mediated genome instability) subcomplex (RMI1 and RMI2). We describe the crystal structure of the RMI core complex, comprising RMI2 and the C-terminal OB domain of RMI1. The overall RMI core structure strongly resembles two-thirds of the trimerization core of the eukaryotic single-stranded DNA-binding protein, Replication Protein A. Immunoprecipitation experiments with RMI2 variants confirm key interactions that stabilize the RMI core interface. Disruption of this interface leads to a dramatic increase in cellular sister chromatid exchange events similar to that seen in BLM-deficient cells. The RMI core interface is therefore crucial for BLM dissolvasome assembly and may have additional cellular roles as a docking hub for other proteins.

  3. Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom's syndrome

    DEFF Research Database (Denmark)

    Suhasini, Avvaru N; Rawtani, Nina A; Wu, Yuliang

    2011-01-01

    Bloom's syndrome (BS) and Fanconi anemia (FA) are autosomal recessive disorders characterized by cancer and chromosomal instability. BS and FA group J arise from mutations in the BLM and FANCJ genes, respectively, which encode DNA helicases. In this work, FANCJ and BLM were found to interact...

  4. Bloom syndrome, genomic instability and cancer: the SOS-like hypothesis.

    Science.gov (United States)

    Amor-Guéret, Mounira

    2006-05-08

    Bloom syndrome (BS) displays one of the strongest known correlations between chromosomal instability and an increased risk of malignancy at an early age. The prevention of genomic instability and cancer depends on a complex network of pathways induced in response to DNA damage and stalled replication forks, including cell-cycle checkpoints, DNA repair, and apoptosis. Several studies have demonstrated that BLM is involved in the cellular response to DNA damage and stalled replication forks. BLM interacts physically and functionally with several proteins involved in the maintenance of genome integrity and BLM is redistributed and/or phosphorylated in response to several genotoxic stresses. The data concerning the relationship between BLM and these cellular pathways are summarized and the role of BLM in the rescue of arrested replication forks is discussed. Moreover, I speculate that BLM deficiency is lethal, and that BLM-deficient cells escaping apoptotic death do so by constitutively inducing a bacterial SOS-like response including the induction of alternative replication pathway(s) dependent on recombination, contributing to the mutator and hyper-Rec phenotypes characteristic of BS cells. This mechanism may be dependent on the RAD51 gene family, and involved in carcinogenesis in the general population.

  5. A wild-type DNA ligase I gene is expressed in Bloom's syndrome cells.

    OpenAIRE

    Petrini, J H; Huwiler, K G; Weaver, D T

    1991-01-01

    Alteration of DNA ligase I activity is a consistent biochemical feature of Bloom's syndrome (BS) cells. DNA ligase I activity in BS cells either is reduced and abnormally thermolabile or is present in an anomalously dimeric form. To assess the role of DNA ligase function in the etiology of BS, we have cloned the DNA ligase I cDNA from normal human cells by a PCR strategy using degenerate oligonucleotide primers based on conserved regions of the Saccharomyces cerevisiae and Schizosaccharomyces...

  6. Discrepant outcomes in two Brazilian patients with Bloom syndrome and Wilms' tumor: two case reports.

    Science.gov (United States)

    Moreira, Marilia Borges; Quaio, Caio Robledo Dc; Zandoná-Teixeira, Aline Cristina; Novo-Filho, Gil Monteiro; Zanardo, Evelin Aline; Kulikowski, Leslie Domenici; Kim, Chong Ae

    2013-12-30

    Bloom syndrome is a rare, autosomal recessive, chromosomal instability disorder caused by mutations in the BLM gene that increase the risk of developing neoplasias, particularly lymphomas and leukemias, at an early age. Case 1 was a 10-year-old Brazilian girl, the third child of a non-consanguineous non-Jewish family, who was born at 36 weeks of gestation and presented with severe intrauterine growth restriction. She had Bloom syndrome and was diagnosed with a unilateral Wilms' tumor at the age of 3.5 years. She responded well to oncological treatment and has remained disease-free for the last 17 years. Case 2 was a 2-year-old Brazilian girl born to non-Jewish first-degree cousins. Her gestation was marked by intrauterine growth restriction. She had Bloom syndrome; a unilateral stage II Wilms' tumor was diagnosed at the age of 4 years after the evaluation of a sudden onset abdominal mass. Surgical removal, neoadjuvant chemotherapy and radiotherapy were not sufficient to control the neoplasia. The tumor recurred after 8 months and she died from clinical complications. Our study reports the importance of rapid diagnostics and clinical follow-up of these patients.

  7. The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants.

    Science.gov (United States)

    Imamura, Osamu; Campbell, Judith L

    2003-07-08

    Bloom syndrome is a disorder of profound and early cancer predisposition in which cells become hypermutable, exhibit high frequency of sister chromatid exchanges, and show increased micronuclei. BLM, the gene mutated in Bloom syndrome, has been cloned previously, and the BLM protein is a member of the RecQ family of DNA helicases. Many lines of evidence suggest that BLM is involved either directly in DNA replication or in surveillance during DNA replication, but its specific roles remain unknown. Here we show that hBLM can suppress both the temperature-sensitive growth defect and the DNA damage sensitivity of the yeast DNA replication mutant dna2-1. The dna2-1 mutant is defective in a helicase-nuclease that is required either to coordinate with the crucial Saccharomyces cerevisiae (sc) FEN1 nuclease in Okazaki fragment maturation or to compensate for scFEN1 when its activity is impaired. We show that human BLM interacts with both scDna2 and scFEN1 by using coimmunoprecipitation from yeast extracts, suggesting that human BLM participates in the same steps of DNA replication or repair as scFEN1 and scDna2.

  8. Early-onset drusen in a girl with bloom syndrome: probable clinical importance of an ocular manifestation.

    Science.gov (United States)

    Aslan, Deniz; Oztürk, Gülyüz; Kaya, Zühre; Bideci, Aysun; Ozdogãan, Sibel; Ozdek, Sengül; Gürsel, Türkiz

    2004-04-01

    Ophthalmic examination of a girl admitted with the complaint of growth failure revealed retinal hard drusen. It was surprising to observe drusen in a child because they represent an age-related degenerative change in normal individuals. After further evaluation, she was diagnosed to have Bloom syndrome, a premature aging syndrome. To the authors' knowledge, this is the first case of Bloom syndrome associated with drusen. It is probable that not only aging but also other fundamental cell processes, especially uncontrolled cell proliferation, might be similarly affected and might follow a more rapid course in this inherited condition presenting with drusen. The authors suggest paying extra attention to drusen during the ophthalmic assessment in the diagnosis of all Bloom syndrome patients; it may be prudent to watch more carefully for the development of cancer in patients with drusen than those without drusen.

  9. Absence of p53 enhances growth defects and etoposide sensitivity of human cells lacking the Bloom syndrome helicase BLM.

    Science.gov (United States)

    So, Sairei; Adachi, Noritaka; Koyama, Hideki

    2007-07-01

    The Bloom syndrome helicase BLM and the tumor-suppressor protein p53 play important roles in preserving genome integrity. Here, we knock out the genes for BLM and p53 in a human pre-B-cell line, Nalm-6. We show that p53 plays an important role in cell proliferation, but not apoptosis, when BLM is absent. Intriguingly, despite the apoptotic function of p53, BLM(/)TP53(/) cells were more sensitive than either single mutant to etoposide, an anticancer agent that poisons DNA topoisomerase II. Our results suggest a direct, BLM-independent role for p53 in etoposide-induced, topoisomerase II-mediated DNA damage in human cells.

  10. Lens opacities in Bloom syndrome: case report and review of the literature.

    Science.gov (United States)

    Cefle, Kivanc; Ozturk, Sukru; Gozum, Nilufer; Duman, Nilgun; Mantar, Ferhan; Guler, Kerim; Palanduz, Sukru

    2007-09-01

    Bloom syndrome is an autosomal recessive disorder characterized by proportionate short stature, photosensitivity, immunodeficiency, hypogonadism and a tendency to develop various malignancies. The greatly increased frequency of sister chromatid exchanges (reciprocal exchange of homologous segments between the two sister chromatids of a chromosome) is regarded as pathognomonic for BS. We describe an 18-year old girl who presented with short stature. She was diagnosed with BS based on an extremely increased frequency of sister chromatid exchanges. Ophthalmological examination revealed mild lens opacities bilaterally, which, to our knowledge, has not been previously reported to be associated with BS.

  11. Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome.

    Science.gov (United States)

    Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

    2013-09-18

    Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress.

  12. Bloom综合征1例%Bloom syndrome:a case report

    Institute of Scientific and Technical Information of China (English)

    郭静; 杨瑞; 郝雁杰; 丁黎; 徐平; 贾惠临

    2014-01-01

    A 17-year-old girl with facial telangiectasis for 17 years is presented. She had multiple military-sized red papules on her face with telangiectasis since 40 days after birth. The histopathology was consistent with the Bloom syndrome.%患者,女,17岁。面部毛细血管扩张17年。出生40天出现面部多发粟粒大红色丘疹,伴毛细血管扩张。系统检查正常。组织病理改变符合Bloom综合征。

  13. Roles of Werner syndrome protein in protection of genome integrity

    DEFF Research Database (Denmark)

    Rossi, Marie L; Ghosh, Avik K; Bohr, Vilhelm A

    2010-01-01

    Werner syndrome protein (WRN) is one of a family of five human RecQ helicases implicated in the maintenance of genome stability. The conserved RecQ family also includes RecQ1, Bloom syndrome protein (BLM), RecQ4, and RecQ5 in humans, as well as Sgs1 in Saccharomyces cerevisiae, Rqh1...... syndrome (WS). WRN is one of the best characterized of the RecQ helicases and is known to have roles in DNA replication and repair, transcription, and telomere maintenance. Studies both in vitro and in vivo indicate that the roles of WRN in a variety of DNA processes are mediated by post...

  14. Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome DNA helicase

    Directory of Open Access Journals (Sweden)

    Paric Enesa

    2003-10-01

    Full Text Available Abstract Background Bloom syndrome is one of the most cancer-predisposing disorders and is characterized by genomic instability and a high frequency of sister chromatid exchange. The disorder is caused by loss of function of a 3' to 5' RecQ DNA helicase, BLM. The exact role of BLM in maintaining genomic integrity is not known but the helicase has been found to associate with several DNA repair complexes and some DNA replication foci. Results Chromatin immunoprecipitation of BLM complexes recovered telomere and ribosomal DNA repeats. The N-terminus of BLM, required for NB localization, is the same as the telomere association domain of BLM. The C-terminus is required for ribosomal DNA localization. BLM localizes primarily to the non-transcribed spacer region of the ribosomal DNA repeat where replication forks initiate. Bloom syndrome cells expressing the deletion alleles lacking the ribosomal DNA and telomere association domains have altered cell cycle populations with increased S or G2/M cells relative to normal. Conclusion These results identify telomere and ribosomal DNA repeated sequence elements as chromosomal targets for the BLM DNA helicase during the S/G2 phase of the cell cycle. BLM is localized in nuclear bodies when it associates with telomeric repeats in both telomerase positive and negative cells. The BLM DNA helicase participates in genomic stability at ribosomal DNA repeats and telomeres.

  15. Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome DNA helicase.

    Science.gov (United States)

    Schawalder, James; Paric, Enesa; Neff, Norma F

    2003-10-27

    Bloom syndrome is one of the most cancer-predisposing disorders and is characterized by genomic instability and a high frequency of sister chromatid exchange. The disorder is caused by loss of function of a 3' to 5' RecQ DNA helicase, BLM. The exact role of BLM in maintaining genomic integrity is not known but the helicase has been found to associate with several DNA repair complexes and some DNA replication foci. Chromatin immunoprecipitation of BLM complexes recovered telomere and ribosomal DNA repeats. The N-terminus of BLM, required for NB localization, is the same as the telomere association domain of BLM. The C-terminus is required for ribosomal DNA localization. BLM localizes primarily to the non-transcribed spacer region of the ribosomal DNA repeat where replication forks initiate. Bloom syndrome cells expressing the deletion alleles lacking the ribosomal DNA and telomere association domains have altered cell cycle populations with increased S or G2/M cells relative to normal. These results identify telomere and ribosomal DNA repeated sequence elements as chromosomal targets for the BLM DNA helicase during the S/G2 phase of the cell cycle. BLM is localized in nuclear bodies when it associates with telomeric repeats in both telomerase positive and negative cells. The BLM DNA helicase participates in genomic stability at ribosomal DNA repeats and telomeres.

  16. Prevalence of breast and colorectal cancer in Ashkenazi Jewish carriers of Fanconi anemia and Bloom syndrome.

    Science.gov (United States)

    Baris, Hagit N; Kedar, Inbal; Halpern, Gabrielle J; Shohat, Tamy; Magal, Nurit; Ludman, Mark D; Shohat, Mordechai

    2007-12-01

    Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ahshkenazi Jews: c.711+4A-->T (IVS4 +4 A-->T) in FACC and BLM(Ash) in Bloom syndrome. Individuals affected by either of these syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk. To estimate the cancer rate among FACC and BLM(Ash) carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals. We studied 42 FACC carriers, 28 BLM(Ash) carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM(Ash). All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM(Ash) and controls were computed and compared using the chi-square test. In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM(Ash) carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%). We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.

  17. Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes

    DEFF Research Database (Denmark)

    Newman, Joseph A; Savitsky, Pavel; Allerston, Charles K;

    2015-01-01

    Bloom's syndrome helicase (BLM) is a member of the RecQ family of DNA helicases, which play key roles in the maintenance of genome integrity in all organism groups. We describe crystal structures of the BLM helicase domain in complex with DNA and with an antibody fragment, as well as SAXS...

  18. Spontaneous and induced chromosomal damage and mutations in Bloom Syndrome mice.

    Science.gov (United States)

    Wang, Yanping; Heddle, John A

    2004-10-04

    Bloom Syndrome (BS) is characterized by both cancer and genomic instability, including chromosomal aberrations, sister chromosome exchanges, and mutations. Since BS heterozygotes are much more frequent than homozygotes, the issue of the sensitivity of heterozygotes to cancer is an important one. This and many other questions concerning the effects of BLM (the gene responsible for the BS) are more easily studied in mice than in humans. To gain insight into genomic instability associated with loss of function of BLM, which codes for a DNA helicase, we compared frequencies of micronuclei, somatic mutations, and loss of heterozygosity (LOH) in Blmtm3Brd homozygous, heterozygous, and wild-type mice carrying a cII transgenic reporter gene. It should be noted that the Blmtm3Brd is inserted into the endogenous locus with a partial duplication of the gene, so some function of the locus may be retained. The cII reporter gene was introduced from the Big Blue mouse by crossing them with Blmtm3Brd mice. All measurements were made on F2 mice from this cross. The reticulocytes of Blmtm3Brd homozygous mice had more micronuclei than heterozygous or wild-type mice (4.5, 2.7, and 2.5 per thousand, respectively; P 0.05). Mutation measurements were also made on mice that had been treated with ethyl-nitrosourea (ENU) because Bloom Syndrome cells are sensitive to ethylating agents. The ENU-induced mutation frequency in Blmtm3Brd homozygous, heterozygous, and wild mice were 54 x 10(-5), 35 x 10(-5), and 25 x 10(-5) mutants/plaques, respectively. ENU induced more mutations in Blmtm3Brd homozygous mice than in wild-type mice (P Bloom Syndrome except that they have normal frequencies of spontaneous mutation. The fact that these mice have elevated rates of both cancer and chromosomal aberrations (as shown by more micronuclei and LOH) but normal rates of spontaneous mutation, shows the greater importance of chromosomal events than mutations in the origin of their cancers.

  19. Bromodeoxyuridine does not contribute to sister chromatid exchange events in normal or Bloom syndrome cells.

    Science.gov (United States)

    van Wietmarschen, Niek; Lansdorp, Peter M

    2016-08-19

    Sister chromatid exchanges (SCEs) are considered sensitive indicators of genome instability. Detection of SCEs typically requires cells to incorporate bromodeoxyuridine (BrdU) during two rounds of DNA synthesis. Previous studies have suggested that SCEs are induced by DNA replication over BrdU-substituted DNA and that BrdU incorporation alone could be responsible for the high number of SCE events observed in cells from patients with Bloom syndrome (BS), a rare genetic disorder characterized by marked genome instability and high SCE frequency. Here we show using Strand-seq, a single cell DNA template strand sequencing technique, that the presence of variable BrdU concentrations in the cell culture medium and in DNA template strands has no effect on SCE frequency in either normal or BS cells. We conclude that BrdU does not induce SCEs and that SCEs detected in either normal or BS cells reflect DNA repair events that occur spontaneously.

  20. Relatively common mutations of the Bloom syndrome gene in the Japanese population.

    Science.gov (United States)

    Kaneko, Hideo; Isogai, Kouji; Fukao, Toshiyuki; Matsui, Eiko; Kasahara, Kimiko; Yachie, Akihiro; Seki, Hidetoshi; Koizumi, Shoichi; Arai, Masami; Utunomiya, Joji; Miki, Yoshio; Kondo, Naomi

    2004-09-01

    Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized by lupus-like erythematous facial telangiectasia, sun sensitivity, infertility, stunted growth and a high predisposition to various types of cancer. Chromosomal abnormalities are hallmarks of this disorder, and high frequencies of sister chromatid exchanges and quadriradial configurations in lymphocytes and fibroblasts are diagnostic features. BLM is the causative gene for BS. We investigated the mutation in the BLM gene in 4 Japanese BS kindreds. Taken together with previously documented mutations, 2 kindreds were homozygous for 631delCAA and 2 were compound heterozygous for 631delCAA. The silent mutation of A1055C (Thr to Thr) was detected in control Japanese individuals. The 6-bp deletion/7-bp insertion at position 2,281, which most Askenazi Jewish BS patients carry, was not detected in 200 Japanese alleles. These results suggest that 631delCAA is a relatively common mutation among the Japanese BS patients.

  1. Dephosphorylation and subcellular compartment change of the mitotic Bloom's syndrome DNA helicase in response to ionizing radiation.

    Science.gov (United States)

    Dutertre, Stéphanie; Sekhri, Redha; Tintignac, Lionel A; Onclercq-Delic, Rosine; Chatton, Bruno; Jaulin, Christian; Amor-Guéret, Mounira

    2002-02-22

    Bloom's syndrome is a rare human autosomal recessive disorder that combines a marked genetic instability and an increased risk of developing all types of cancers and which results from mutations in both copies of the BLM gene encoding a RecQ 3'-5' DNA helicase. We recently showed that BLM is phosphorylated and excluded from the nuclear matrix during mitosis. We now show that the phosphorylated mitotic BLM protein is associated with a 3'-5' DNA helicase activity and interacts with topoisomerase III alpha. We demonstrate that in mitosis-arrested cells, ionizing radiation and roscovitine treatment both result in the reversion of BLM phosphorylation, suggesting that BLM could be dephosphorylated through the inhibition of cdc2 kinase. This was supported further by our data showing that cdc2 kinase activity is inhibited in gamma-irradiated mitotic cells. Finally we show that after ionizing radiation, BLM is not involved in the establishment of the mitotic DNA damage checkpoint but is subjected to a subcellular compartment change. These findings lead us to propose that BLM may be phosphorylated during mitosis, probably through the cdc2 pathway, to form a pool of rapidly available active protein. Inhibition of cdc2 kinase after ionizing radiation would lead to BLM dephosphorylation and possibly to BLM recruitment to some specific sites for repair.

  2. Mutational analysis of Bloom helicase.

    Science.gov (United States)

    Xi, Xu Guang

    2010-01-01

    DNA helicases are biomolecular motors that convert the chemical energy derived from the hydrolysis of nucleotide triphosphate (usually ATP) into mechanical energy to unwind double-stranded DNA. The unwinding of double-stranded DNA is an essential process for DNA replication, repair, recombination, and transcription. Mutations in human RecQ helicases result in inherent human disease including Bloom's syndrome, Werner's syndrome, and Rothmund-Thomson syndrome. Bloom's syndrome (BS) is a rare human autosomal recessive disorder characterized by a strong predisposition to a wide range of cancers commonly affecting the general population. In order to understand the molecular basis of BS pathology and the mechanism underlying the function of Bloom helicase, we have analyzed BS-causing missense mutations by a combination of structural modeling, site-directed mutagenesis, and biochemical and biophysical approaches. Here, we describe the methods and protocols for measuring ATPase, ATP and DNA binding, DNA strand annealing, and DNA unwinding activities of Bloom protein and its mutant variants. These approaches should be applicable and useful for studying other helicases.

  3. Bloom syndrome complex promotes FANCM recruitment to stalled replication forks and facilitates both repair and traverse of DNA interstrand crosslinks.

    Science.gov (United States)

    Ling, Chen; Huang, Jing; Yan, Zhijiang; Li, Yongjiang; Ohzeki, Mioko; Ishiai, Masamichi; Xu, Dongyi; Takata, Minoru; Seidman, Michael; Wang, Weidong

    2016-01-01

    The recruitment of FANCM, a conserved DNA translocase and key component of several DNA repair protein complexes, to replication forks stalled by DNA interstrand crosslinks (ICLs) is a step upstream of the Fanconi anemia (FA) repair and replication traverse pathways of ICLs. However, detection of the FANCM recruitment has been technically challenging so that its mechanism remains exclusive. Here, we successfully observed recruitment of FANCM at stalled forks using a newly developed protocol. We report that the FANCM recruitment depends upon its intrinsic DNA translocase activity, and its DNA-binding partner FAAP24. Moreover, it is dependent on the replication checkpoint kinase, ATR; but is independent of the FA core and FANCD2-FANCI complexes, two essential components of the FA pathway, indicating that the FANCM recruitment occurs downstream of ATR but upstream of the FA pathway. Interestingly, the recruitment of FANCM requires its direct interaction with Bloom syndrome complex composed of BLM helicase, Topoisomerase 3α, RMI1 and RMI2; as well as the helicase activity of BLM. We further show that the FANCM-BLM complex interaction is critical for replication stress-induced FANCM hyperphosphorylation, for normal activation of the FA pathway in response to ICLs, and for efficient traverse of ICLs by the replication machinery. Epistasis studies demonstrate that FANCM and BLM work in the same pathway to promote replication traverse of ICLs. We conclude that FANCM and BLM complex work together at stalled forks to promote both FA repair and replication traverse pathways of ICLs.

  4. Bloom syndrome helicase stimulates RAD51 DNA strand exchange activity through a novel mechanism.

    Science.gov (United States)

    Bugreev, Dmitry V; Mazina, Olga M; Mazin, Alexander V

    2009-09-25

    Loss or inactivation of BLM, a helicase of the RecQ family, causes Bloom syndrome, a genetic disorder with a strong predisposition to cancer. Although the precise function of BLM remains unknown, genetic data has implicated BLM in the process of genetic recombination and DNA repair. Previously, we demonstrated that BLM can disrupt the RAD51-single-stranded DNA filament that promotes the initial steps of homologous recombination. However, this disruption occurs only if RAD51 is present in an inactive ADP-bound form. Here, we investigate interactions of BLM with the active ATP-bound form of the RAD51-single-stranded DNA filament. Surprisingly, we found that BLM stimulates DNA strand exchange activity of RAD51. In contrast to the helicase activity of BLM, this stimulation does not require ATP hydrolysis. These data suggest a novel BLM function that is stimulation of the RAD51 DNA pairing. Our results demonstrate the important role of the RAD51 nucleoprotein filament conformation in stimulation of DNA pairing by BLM.

  5. Enhancement of microhomology-mediated genomic rearrangements by transient loss of mouse Bloom syndrome helicase.

    Science.gov (United States)

    Yamanishi, Ayako; Yusa, Kosuke; Horie, Kyoji; Tokunaga, Masahiro; Kusano, Kohji; Kokubu, Chikara; Takeda, Junji

    2013-09-01

    Bloom syndrome, an autosomal recessive disorder of the BLM gene, confers predisposition to a broad spectrum of early-onset cancers in multiple tissue types. Loss of genomic integrity is a primary hallmark of such human malignancies, but many studies using disease-affected specimens are limited in that they are retrospective and devoid of an appropriate experimental control. To overcome this, we devised an experimental system to recapitulate the early molecular events in genetically engineered mouse embryonic stem cells, in which cells undergoing loss of heterozygosity (LOH) can be enriched after inducible down-regulation of Blm expression, with or without site-directed DNA double-strand break (DSB) induction. Transient loss of BLM increased the rate of LOH, whose breakpoints were distributed along the chromosome. Combined with site-directed DSB induction, loss of BLM synergistically increased the rate of LOH and concentrated the breakpoints around the targeted chromosomal region. We characterized the LOH events using specifically tailored genomic tools, such as high-resolution array comparative genomic hybridization and high-density single nucleotide polymorphism genotyping, revealing that the combination of BLM suppression and DSB induction enhanced genomic rearrangements, including deletions and insertions, whose breakpoints were clustered in genomic inverted repeats and associated with junctional microhomologies. Our experimental approach successfully uncovered the detailed molecular mechanisms of as-yet-uncharacterized loss of heterozygosities and reveals the significant contribution of microhomology-mediated genomic rearrangements, which could be widely applicable to the early steps of cancer formation in general.

  6. Bloom syndrome radials are predominantly non-homologous and are suppressed by phosphorylated BLM.

    Science.gov (United States)

    Owen, Nichole; Hejna, James; Rennie, Scott; Mitchell, Asia; Hanlon Newell, Amy; Ziaie, Navid; Moses, Robb E; Olson, Susan B

    2014-01-01

    Biallelic mutations in BLM cause Bloom syndrome (BS), a genome instability disorder characterized by growth retardation, sun sensitivity and a predisposition to cancer. As evidence of decreased genome stability, BS cells demonstrate not only elevated levels of spontaneous sister chromatid exchanges (SCEs), but also exhibit chromosomal radial formation. The molecular nature and mechanism of radial formation is not known, but radials have been thought to be DNA recombination intermediates between homologs that failed to resolve. However, we find that radials in BS cells occur over 95% between non-homologous chromosomes, and occur non-randomly throughout the genome. BLM must be phosphorylated at T99 and T122 for certain cell cycle checkpoints, but it is not known whether these modifications are necessary to suppress radial formation. We find that exogenous BLM constructs preventing phosphorylation at T99 and T122 are not able to suppress radial formation in BS cells, but are able to inhibit SCE formation. These findings indicate that BLM functions in 2 distinct pathways requiring different modifications. In one pathway, for which the phosphorylation marks appear dispensable, BLM functions to suppress SCE formation. In a second pathway, T99 and T122 phosphorylations are essential for suppression of chromosomal radial formation, both those formed spontaneously and those formed following interstrand crosslink damage.

  7. Somatic hypermutation of immunoglobulin genes is independent of the Bloom's syndrome DNA helicase.

    Science.gov (United States)

    Sack, S Z; Liu, Y; German, J; Green, N S

    1998-05-01

    Immunoglobulin gene somatic mutation leads to antibody affinity maturation through the introduction of multiple point mutations in the antigen binding site. No genes have as yet been identified that participate in this process. Bloom's syndrome (BS) is a chromosomal breakage disorder with a mutator phenotype. Most affected individuals exhibit an immunodeficiency of undetermined aetiology. The gene for this disorder, BLM, has recently been identified as a DNA helicase. If this gene were to play a role in immunoglobulin mutation, then people with BS may lack normally mutated antibodies. Since germ-line, non-mutated immunoglobulin genes generally produce low affinity antibodies, impaired helicase activity might be manifested as the immunodeficiency found in BS. Therefore, we asked whether BLM is specifically involved in immunoglobulin hypermutation. Sequences of immunoglobulin variable (V) regions were analysed from small unsorted blood samples obtained from BS individuals and compared with germ-line sequences. BS V regions displayed the normal distribution of mutations, indicating that the defect in BS is not related to the mechanism of somatic mutation. These data strongly argue against BLM being involved in this process. The genetic approach to identifying the genes involved in immunoglobulin mutation will require further studies of DNA repair- and immunodeficient individuals.

  8. Oxidative stress, mitochondrial abnormalities and antioxidant defense in Ataxia-telangiectasia, Bloom syndrome and Nijmegen breakage syndrome

    Directory of Open Access Journals (Sweden)

    Mateusz Maciejczyk

    2017-04-01

    Full Text Available Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T, Bloom syndrome (BS and Nijmegen breakage syndrome (NBS are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Recent studies indicate new, alternative sources of oxidative stress in A-T, BS and NBS cells, including NADPH oxidase 4 (NOX4, oxidised low-density lipoprotein (ox-LDL or Poly (ADP-ribose polymerases (PARP. Mitochondrial abnormalities such as changes in the ultrastructure and function of mitochondria, excess mROS production as well as mitochondrial damage have also been reported in A-T, BS and NBS cells. A-T, BS and NBS cells are inextricably linked to high levels of reactive oxygen species (ROS, and thereby, chronic oxidative stress may be a major phenotypic hallmark in these diseases. Due to the presence of mitochondrial disturbances, A-T, BS and NBS may be considered mitochondrial diseases. Excess activity of antioxidant enzymes and an insufficient amount of low molecular weight antioxidants indicate new pharmacological strategies for patients suffering from the aforementioned diseases. However, at the current stage of research we are unable to ascertain if antioxidants and free radical scavengers can improve the condition or prolong the survival time of A-T, BS and NBS patients. Therefore, it is necessary to conduct experimental studies in a human model.

  9. Oxidative stress, mitochondrial abnormalities and antioxidant defense in Ataxia-telangiectasia, Bloom syndrome and Nijmegen breakage syndrome.

    Science.gov (United States)

    Maciejczyk, Mateusz; Mikoluc, Bozena; Pietrucha, Barbara; Heropolitanska-Pliszka, Edyta; Pac, Malgorzata; Motkowski, Radosław; Car, Halina

    2017-04-01

    Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Recent studies indicate new, alternative sources of oxidative stress in A-T, BS and NBS cells, including NADPH oxidase 4 (NOX4), oxidised low-density lipoprotein (ox-LDL) or Poly (ADP-ribose) polymerases (PARP). Mitochondrial abnormalities such as changes in the ultrastructure and function of mitochondria, excess mROS production as well as mitochondrial damage have also been reported in A-T, BS and NBS cells. A-T, BS and NBS cells are inextricably linked to high levels of reactive oxygen species (ROS), and thereby, chronic oxidative stress may be a major phenotypic hallmark in these diseases. Due to the presence of mitochondrial disturbances, A-T, BS and NBS may be considered mitochondrial diseases. Excess activity of antioxidant enzymes and an insufficient amount of low molecular weight antioxidants indicate new pharmacological strategies for patients suffering from the aforementioned diseases. However, at the current stage of research we are unable to ascertain if antioxidants and free radical scavengers can improve the condition or prolong the survival time of A-T, BS and NBS patients. Therefore, it is necessary to conduct experimental studies in a human model. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Interaction of Werner and Bloom syndrome genes with p53 in familial breast cancer.

    Science.gov (United States)

    Wirtenberger, Michael; Frank, Bernd; Hemminki, Kari; Klaes, Rüdiger; Schmutzler, Rita K; Wappenschmidt, Barbara; Meindl, Alfons; Kiechle, Marion; Arnold, Norbert; Weber, Bernhard H F; Niederacher, Dieter; Bartram, Claus R; Burwinkel, Barbara

    2006-08-01

    Mutations of the human RecQ helicase genes WRN and BLM lead to rare autosomal recessive disorders, Werner and Bloom syndromes, which are associated with premature ageing and cancer predisposition. We tested the hypothesis whether three polymorphic, non-conservative amino acid exchanges in WRN and BLM act as low-penetrance familial breast cancer risk factors. Moreover, we examined the putative impact of p53 MspI 1798G>A, which is completely linked to p53PIN3, a 16 bp insertion/duplication that has been associated with reduced p53 expression, on familial breast cancer risk. Genotyping analyses, performed on 816 BRCA1/2 mutation-negative German familial breast cancer patients and 1012 German controls, revealed a significant association of the WRN Cys1367Arg polymorphism with familial breast cancer (OR = 1.28, 95% CI 1.06-1.54) and high-risk familial breast cancer (OR = 1.32, 95% CI 1.06-1.65). The analysis of p53 MspI 1798G>A, which is completely linked to p53PIN3, showed a significantly increased familial breast cancer risk for carriers of the 16 bp insertion/duplication, following a recessive mode (OR = 2.15, 95% CI = 1.12-4.11). WRN Cys1367Arg, located in the C-terminus, the binding site of p53, is predicted to be damaging. The joint effect of WRN Cys1367Arg and p53 MspI resulted in an increased breast cancer risk compared to the single polymorphisms (OR = 3.39, 95% CI 1.19-9.71). In conclusion, our study indicates the importance of inherited variants in the WRN and p53 genes for familial breast cancer susceptibility.

  11. Adenocarcinoma of the Right Colon in a Patient with Bloom Syndrome.

    Science.gov (United States)

    Martinez, Carlos Augusto Real; Pinheiro, Lilian Vital; Rossi, Debora Helena; Camargo, Michel Gardere; Ayrizono, Maria de Lourdes Setsuko; Leal, Raquel Franco; Coy, Cláudio Saddy Rodrigues

    2016-01-01

    Introduction. Bloom syndrome (BS) is an inherited disorder due to mutation in BLM gene. The diagnosis of BS should be considered in patients with growth retardation of prenatal onset, a photosensitive rash in a butterfly distribution over the cheeks, and an increased risk of cancer at an early age. Clinical manifestations also include short stature, dolichocephaly, prominent ears, micrognathia, malar hypoplasia and a high-pitched voice, immunodeficiency, type II diabetes, and hypogonadism associated with male infertility and female subfertility. The aim of this report is to describe case of patient with BS who developed adenocarcinoma of the cecum, successfully treated by right colectomy. Case Report. A 40-year-old man underwent colonoscopy to investigate the cause of his diarrhea, weight loss, and anemia. The patient knew that he was a carrier of BS diagnosed at young age. The colonoscopy showed an expansive and vegetating mass with 5.5 cm in diameter, located within the ascending colon. Histopathological analysis of tissue fragments collected during colonoscopy confirmed the presence of tubular adenocarcinoma, and he was referred for an oncological right colectomy. The procedure was performed without complications, and the patient was discharged on the fifth postoperative day. Histopathological examination of the surgical specimen confirmed the presence of a grade II tubular adenocarcinoma (stage IIA). The patient is currently well five years after surgery, without clinical or endoscopic signs of relapse in a multidisciplinary approach for the monitoring of comorbidities related to BS. Conclusion. Despite the development of colorectal cancer to be, a possibility rarely described the present case shows the need for early screening for colorectal cancer in all patients affected by BS.

  12. Adenocarcinoma of the Right Colon in a Patient with Bloom Syndrome

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    Carlos Augusto Real Martinez

    2016-01-01

    Full Text Available Introduction. Bloom syndrome (BS is an inherited disorder due to mutation in BLM gene. The diagnosis of BS should be considered in patients with growth retardation of prenatal onset, a photosensitive rash in a butterfly distribution over the cheeks, and an increased risk of cancer at an early age. Clinical manifestations also include short stature, dolichocephaly, prominent ears, micrognathia, malar hypoplasia and a high-pitched voice, immunodeficiency, type II diabetes, and hypogonadism associated with male infertility and female subfertility. The aim of this report is to describe case of patient with BS who developed adenocarcinoma of the cecum, successfully treated by right colectomy. Case Report. A 40-year-old man underwent colonoscopy to investigate the cause of his diarrhea, weight loss, and anemia. The patient knew that he was a carrier of BS diagnosed at young age. The colonoscopy showed an expansive and vegetating mass with 5.5 cm in diameter, located within the ascending colon. Histopathological analysis of tissue fragments collected during colonoscopy confirmed the presence of tubular adenocarcinoma, and he was referred for an oncological right colectomy. The procedure was performed without complications, and the patient was discharged on the fifth postoperative day. Histopathological examination of the surgical specimen confirmed the presence of a grade II tubular adenocarcinoma (stage IIA. The patient is currently well five years after surgery, without clinical or endoscopic signs of relapse in a multidisciplinary approach for the monitoring of comorbidities related to BS. Conclusion. Despite the development of colorectal cancer to be, a possibility rarely described the present case shows the need for early screening for colorectal cancer in all patients affected by BS.

  13. Successful treatment of mature B-cell lymphoma with rituximab-based chemotherapy in a patient with Bloom syndrome.

    Science.gov (United States)

    Jastaniah, Wasil

    2017-07-01

    This report presents a case of Bloom syndrome (BS) in a consanguineous Saudi family. The patient, an 11-year-old male with mature B-cell lymphoma, had minimal therapeutic response and significant dose-limiting toxicity with standard chemotherapy treatment. He later responded successfully to a rituximab-based chemotherapy protocol. This case highlights that the rituximab-based chemotherapy protocol is an effective and safe treatment alternative for mature B-cell lymphoma in patients with BS. Further trials are warranted to investigate this modality of treatment. © 2016 Wiley Periodicals, Inc.

  14. Rate of sister chromatid exchanges in Bloom syndrome fibroblasts reduced by co-cultivation with normal fibroblasts.

    OpenAIRE

    1980-01-01

    Six strains of Bloom syndrome (BlS) fibroblasts responded to co-cultivation with normal fibroblasts at a 1:2 ratio by a reduced rate of sister chromatid exchanges (SCE's) from a mean of 67.5 (range = 59--78) to 28.4 (range = 21--35). The response was dose-dependent in one strain tested at 1:2, 1:1, and 2:1 ratios. In addition, quadriradial exchange figures and other signs of increased chromosomal instability were not found in BlS cells following co-cultivation with control cells. Control cell...

  15. 兄弟同患Bloom综合征%Bloom's syndrome in two brothers

    Institute of Scientific and Technical Information of China (English)

    李向花; 王昊; 汪京峡; 杨一飞; 杨文斌; 马梅; 陆敏

    2012-01-01

    例1,男,9岁,回族.颜面、耳廓反复起红斑8年.出生7个月双颧部出现毛细血管扩张性红斑,渐累及耳廓和前臂,双小腿皮肤出现轻度鱼鳞病样外观,5岁时口唇出现水疱、糜烂,皮损夏季日光强烈时出现并渐加重,冬季自行缓解或消失.例2,例1胞弟.男,3岁,回族.颜面部反复起红斑2年.1岁时双颧部开始出现红斑,渐扩延至颊部,伴轻微瘙痒和脱屑,期间,小腿皮肤干燥、脱屑,呈鱼鳞样改变;皮损每于夏季来临时出现,且渐加重,随冬季到来皮损渐消失.2例各系统检查未发现异常,身高正常;实验室、病理及其他辅助检查无有意义的阳性发现,染色体检查正常.患儿父母为姨表近亲结婚,诊断为Bloom综合征.%The patient 1 was a 9-year-old boy of Hui nationality who presented with recurrent erythema over the face and auricles for 8 years.Telangiectasis and erythema developed on both cheeks 7 months after birth,which gradually spread to the auricles,forearms and both legs with a mild ichthyosiform appearance.At 5 years of age blisters and erosions appeared on the lips,which occurred and were aggravated after exposure to strong sunlight during summer and spontaneously subsided or disappeared in winter.The patient 2,a 3-year-old boy who was the younger brother of the patient 1,presented with recurrent erythema for 2 years.At 1 year of age,erythema began to appear on both cheeks and gradually spread to the buccal region,with mild pruritus and scaling.Meanwhile,the skin of both legs was dry and scaling and gave an ichthyosifonn appearance.The lesions usually appeared in early summer and gradually subsided in winter.No abnormality was found by systemic,laboratory,pathological or other auxiliary examination.Chromosomal abnormality was undetected.Body height was normal.The parents of the two siblings were first cousins.Both children were diagnosed with Bloom's syndrome.

  16. Electrophoretic protein profiles of mid-sized copepod Calanoides patagoniensis steadily fed bloom-forming diatoms

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    Victor M Aguilera

    2015-09-01

    Full Text Available Recent field and experimental evidence collected in the southern upwelling region off Concepción (36°5'S, 73°3'W showed an abrupt reduction (<72 h in the egg production rates (EPR of copepods when they were fed steadily and solely with the local bloom-forming diatom Thalassiosira rotula. Because diatoms were biochemically similar to dinoflagellate Prorocentrum minimum, a diet which supported higher reproductive outcomes, the fecundity reduction observed in copepod females fed with the diatom may have obeyed to post-ingestive processes, giving rise to resources reallocation. This hypothesis was tested by comparing feeding (clearance and ingestion rates, reproduction (EPR and hatching success and the structure of protein profiles (i.e., number and intensity of electrophoretic bands of copepods (adults and eggs incubated during 96 h with the two food conditions. The structure of protein profiles included molecular sizes that were calculated from the relative mobility of protein standards against the logarithm of their molecular sizes. After assessing the experimental conditions, feeding decreased over time for those females fed with T. rotula, while reproduction was higher in females fed with P. minimum. Electrophoretic profiles resulted similar mostly at a banding region of 100 to 89-kDa, while they showed partial differences around the region of 56-kDa band, especially in those females fed and eggs produced with T. rotula. Due to reproductive volume was impacted while larvae viability, a physiological processes with specific and high nutritional requirements, was independent on food type; post-ingestive processes, such as expression of stress-related proteins deviating resources to metabolic processes others than reproduction, are discussed under framework of nutritional-toxic mechanisms mediating copepod-diatoms relationships in productive upwelling areas.

  17. The Ashkenazic Jewish Bloom syndrome mutation blmAsh is present in non-Jewish Americans of Spanish ancestry.

    Science.gov (United States)

    Ellis, N A; Ciocci, S; Proytcheva, M; Lennon, D; Groden, J; German, J

    1998-12-01

    Bloom syndrome (BS) is more frequent in the Ashkenazic Jewish population than in any other. There the predominant mutation, referred to as "blmAsh," is a 6-bp deletion and 7-bp insertion at nucleotide position 2281 in the BLM cDNA. Using a convenient PCR assay, we have identified blmAsh on 58 of 60 chromosomes transmitted by Ashkenazic parents to persons with BS. In contrast, in 91 unrelated non-Ashkenazic persons with BS whom we examined, blmAsh was identified only in 5, these coming from Spanish-speaking Christian families from the southwestern United States, Mexico, or El Salvador. These data, along with haplotype analyses, show that blmAsh was independently established through a founder effect in Ashkenazic Jews and in immigrants to formerly Spanish colonies. This striking observation underscores the complexity of Jewish history and demonstrates the importance of migration and genetic drift in the formation of human populations.

  18. Chromosomal instability associated with a novel BLM frameshift mutation (c.1980-1982delAA) in two unrelated Tunisian families with Bloom syndrome.

    Science.gov (United States)

    Ben Salah, G; Salem, I Hadj; Masmoudi, A; Ben Rhouma, B; Turki, H; Fakhfakh, F; Ayadi, H; Kamoun, H

    2014-10-01

    The Bloom syndrome (BS) is an autosomal recessive disorder associated with dwarfism, immunodeficiency, reduced fertility and cancer risk. BS cells show genomic instability, particularly an hyper exchange between the sister chromatids due to a defective processing of the DNA replication intermediates. It is caused by mutations in the BLM gene which encodes a member of the RecQ family of DExH box DNA helicases. In this study, we reported cytogenetic, BLM linkage and mutational analyses for two affected Tunisian families. The Cytogenetic parameters were performed by chromosomal aberration (CA) and sister chromatid exchange (SCE) assays and results showed a significant increase in mean frequency of CA and SCE in BS cells. BLM linkage performed by microsatellite genotyping revealed homozygous haplotypes for the BS patients, evidence of linkage to BLM gene. Mutational analysis by direct DNA sequencing revealed a novel frameshift mutation (c.1980-1982delAA) in exon 8 of BLM gene, resulting in a truncated protein (p.Lys662fsX5). The truncated protein could explain genomic instability and its related symptoms in the BS patients. The screening of this mutation is useful for BS diagnosis confirmation in Tunisian families.

  19. Rif1 provides a new DNA-binding interface for the Bloom syndrome complex to maintain normal replication.

    Science.gov (United States)

    Xu, Dongyi; Muniandy, Parameswary; Leo, Elisabetta; Yin, Jinhu; Thangavel, Saravanabhavan; Shen, Xi; Ii, Miki; Agama, Keli; Guo, Rong; Fox, David; Meetei, Amom Ruhikanta; Wilson, Lauren; Nguyen, Huy; Weng, Nan-ping; Brill, Steven J; Li, Lei; Vindigni, Alessandro; Pommier, Yves; Seidman, Michael; Wang, Weidong

    2010-09-15

    BLM, the helicase defective in Bloom syndrome, is part of a multiprotein complex that protects genome stability. Here, we show that Rif1 is a novel component of the BLM complex and works with BLM to promote recovery of stalled replication forks. First, Rif1 physically interacts with the BLM complex through a conserved C-terminal domain, and the stability of Rif1 depends on the presence of the BLM complex. Second, Rif1 and BLM are recruited with similar kinetics to stalled replication forks, and the Rif1 recruitment is delayed in BLM-deficient cells. Third, genetic analyses in vertebrate DT40 cells suggest that BLM and Rif1 work in a common pathway to resist replication stress and promote recovery of stalled forks. Importantly, vertebrate Rif1 contains a DNA-binding domain that resembles the αCTD domain of bacterial RNA polymerase α; and this domain preferentially binds fork and Holliday junction (HJ) DNA in vitro and is required for Rif1 to resist replication stress in vivo. Our data suggest that Rif1 provides a new DNA-binding interface for the BLM complex to restart stalled replication forks.

  20. Non-Bloom syndrome-associated partial and total loss-of-function variants of BLM helicase.

    Science.gov (United States)

    Mirzaei, Hamed; Schmidt, Kristina H

    2012-11-20

    Bloom syndrome (BS) is an autosomal recessive disorder caused by mutations in the RecQ-like DNA helicase BLM, which functions in the maintenance of genome stability. Using a humanized model of Saccharomyces cerevisiae that expresses a chimera of the N terminus of yeast Sgs1 and the C terminus of human BLM from the chromosomal SGS1 locus, we have functionally evaluated 27 BLM alleles that are not currently known to be associated with BS. We identified nine alleles with impaired function when assessed for hypersensitivity to the DNA-damaging agent hydroxyurea (HU). Six of these alleles (P690L, R717T, W803R, Y811C, F857L, G972V) caused sensitivity to HU that was comparable to known BS-associated or helicase-dead alleles, suggesting that they may cause BS and, in the heterozygous state, act as risk factors for cancerogenesis. We also identified three alleles (R791C, P868L, G1120R) that caused intermediate sensitivity to HU; although unlikely to cause BS, these partial loss-of-function alleles may increase risk for cancers or other BS-associated complications if a person is homozygous or compound heterozygous for these alleles or if they carry a known BS-associated allele.

  1. Differential expression of Werner and Bloom syndrome genes in the peripheral blood of HIV-1 infected patients.

    Science.gov (United States)

    Bordi, Licia; Gioia, Cristiana; Lalle, Eleonora; Piselli, Pierluca; Poccia, Fabrizio; Capobianchi, Maria R; Amendola, Alessandra

    2007-02-01

    Human immunodeficiency virus (HIV)-induced immunodeficiency and immune-system aging share some analogies. Since Werner (WRN) and Bloom (BLM) helicases are crucial in cell repair and aging, their peripheral blood mononuclear cells (PBMC) mRNA levels were compared in HIV-1 infected patients and in normal donors. The mean levels of WRN mRNA were 3.7-fold higher in PBMCs from HIV-1 infected individuals in comparison to healthy donors, whereas BLM mRNA mean levels were slightly higher, although not significantly. WRN increase was positively correlated to CD4 and CD8 T-cell numbers, and also the percentage of naive T lymphocytes, and was observed also in T-cell subsets. Interestingly, a general trend toward increased WRN mRNA levels in individuals with lower viral load was observed, without association with patient age, time of seroconversion, and on/off antiretroviral therapy regimen. On the whole, this study shows that WRN and BLM are differentially modulated in HIV infection, as WRN--but not BLM--is significantly increased, suggesting that mechanisms different from defect or loss of helicase function, observed in WRN and BLM syndromes, may be at the basis of T-cell aging in HIV infection.

  2. Interhomolog recombination and loss of heterozygosity in wild-type and Bloom syndrome helicase (BLM)-deficient mammalian cells.

    Science.gov (United States)

    LaRocque, Jeannine R; Stark, Jeremy M; Oh, Jin; Bojilova, Ekaterina; Yusa, Kosuke; Horie, Kyoji; Takeda, Junji; Jasin, Maria

    2011-07-19

    Genomic integrity often is compromised in tumor cells, as illustrated by genetic alterations leading to loss of heterozygosity (LOH). One mechanism of LOH is mitotic crossover recombination between homologous chromosomes, potentially initiated by a double-strand break (DSB). To examine LOH associated with DSB-induced interhomolog recombination, we analyzed recombination events using a reporter in mouse embryonic stem cells derived from F1 hybrid embryos. In this study, we were able to identify LOH events although they occur only rarely in wild-type cells (≤2.5%). The low frequency of LOH during interhomolog recombination suggests that crossing over is rare in wild-type cells. Candidate factors that may suppress crossovers include the RecQ helicase deficient in Bloom syndrome cells (BLM), which is part of a complex that dissolves recombination intermediates. We analyzed interhomolog recombination in BLM-deficient cells and found that, although interhomolog recombination is slightly decreased in the absence of BLM, LOH is increased by fivefold or more, implying significantly increased interhomolog crossing over. These events frequently are associated with a second homologous recombination event, which may be related to the mitotic bivalent structure and/or the cell-cycle stage at which the initiating DSB occurs.

  3. Loss of the bloom syndrome helicase increases DNA ligase 4-independent genome rearrangements and tumorigenesis in aging Drosophila.

    Science.gov (United States)

    Garcia, Ana Maria; Salomon, Robert N; Witsell, Alice; Liepkalns, Justine; Calder, R Brent; Lee, Moonsook; Lundell, Martha; Vijg, Jan; McVey, Mitch

    2011-12-19

    The BLM DNA helicase plays a vital role in maintaining genome stability. Mutations in BLM cause Bloom syndrome, a rare disorder associated with cancer predisposition and premature aging. Humans and mice with blm mutations have increased frequencies of spontaneous mutagenesis, but the molecular basis of this increase is not well understood. In addition, the effect of aging on spontaneous mutagenesis in blm mutants has not been characterized. To address this, we used a lacZ reporter system in wild-type and several mutant strains of Drosophila melanogaster to analyze mechanisms of mutagenesis throughout their lifespan. Our data show that Drosophila lacking BLM have an elevated frequency of spontaneous genome rearrangements that increases with age. Although in normal flies most genome rearrangements occur through DNA ligase 4-dependent classical end joining, most rearrangements that accumulate during aging in blm mutants do not require DNA ligase 4, suggesting the influence of an alternative end-joining mechanism. Adult blm mutants also display reduced lifespan and ligase 4-independent enhanced tumorigenesis in mitotically active tissues. These results suggest that Drosophila BLM suppresses error-prone alternative end-joining repair of DNA double-strand breaks that can result in genome instability and tumor formation during aging. In addition, since loss of BLM significantly affects lifespan and tumorigenesis, the data provide a link between error-prone end joining, genome rearrangements, and tumor formation in a model metazoan.

  4. Depletion of the bloom syndrome helicase stimulates homology-dependent repair at double-strand breaks in human chromosomes.

    Science.gov (United States)

    Wang, Yibin; Smith, Krissy; Waldman, Barbara Criscuolo; Waldman, Alan S

    2011-04-03

    Mutation of BLM helicase causes Blooms syndrome, a disorder associated with genome instability, high levels of sister chromatid exchanges, and cancer predisposition. To study the influence of BLM on double-strand break (DSB) repair in human chromosomes, we stably transfected a normal human cell line with a DNA substrate that contained a thymidine kinase (tk)-neo fusion gene disrupted by the recognition site for endonuclease I-SceI. The substrate also contained a closely linked functional tk gene to serve as a recombination partner for the tk-neo fusion gene. We derived two cell lines each containing a single integrated copy of the DNA substrate. In these cell lines, a DSB was introduced within the tk-neo fusion gene by expression of I-SceI. DSB repair events that occurred via homologous recombination (HR) or nonhomologous end-joining (NHEJ) were recovered by selection for G418-resistant clones. DSB repair was examined under conditions of either normal BLM expression or reduced BLM expression brought about by RNA interference. We report that BLM knockdown in both cell lines specifically increased the frequency of HR events that produced deletions by crossovers or single-strand annealing while leaving the frequency of gene conversions unchanged or reduced. We observed no change in the accuracy of individual HR events and no substantial alteration of the nature of individual NHEJ events when BLM expression was reduced. Our work provides the first direct evidence that BLM influences DSB repair pathway choice in human chromosomes and suggests that BLM deficiency can engender genomic instability by provoking an increased frequency of HR events of a potentially deleterious nature.

  5. Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype

    Directory of Open Access Journals (Sweden)

    Matei Irina

    2001-08-01

    Full Text Available Abstract Background Genomic instability has been reported at microsatellite tracts in few coding sequences. We have shown that the Bloom syndrome BLM gene may be a target of microsatelliteinstability (MSI in a short poly-adenine repeat located in its coding region. To further characterize the involvement of BLM in tumorigenesis, we have investigated mutations in nine genes containing coding microsatellites in microsatellite mutator phenotype (MMP positive and negative gastric carcinomas (GCs. Methods We analyzed 50 gastric carcinomas (GCs for mutations in the BLM poly(A tract aswell as in the coding microsatellites of the TGFβ1-RII, IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes. Results BLM mutations were found in 27% of MMP+ GCs (4/15 cases but not in any of the MMP negative GCs (0/35 cases. The frequency of mutations in the other eight coding regions microsatellite was the following: TGFβ1-RII (60 %, BAX (27%, hMSH6 (20%,hMSH3 (13%, CBL (13%, IGFIIR (7%, RECQL (0% and WRN (0%. Mutations in BLM appear to be more frequently associated with frameshifts in BAX and in hMSH6and/or hMSH3. Tumors with BLM alterations present a higher frequency of unstable mono- and trinucleotide repeats located in coding regions as compared with mutator phenotype tumors without BLM frameshifts. Conclusions BLM frameshifts are frequent alterations in GCs specifically associated with MMP+tumors. We suggest that BLM loss of function by MSI may increase the genetic instability of a pre-existent unstable genotype in gastric tumors.

  6. [Soluble brain proteins in autosomal trisomy syndromes].

    Science.gov (United States)

    Mikhneva, L M; Baryshevskaia, V D

    1981-01-01

    The authors examined the soluble proteins of the brain frontal lobes in the newborn with trisomias of the 13th, 18th, and 21st chromosomes (Down's, Patau's, and Edwards' syndromes). The examinations were carried out on autopsy material (the post-mortem period not exceeding 24 hours) by the method of disc electrophoresis in polyacrylamide gel. The brain tissue was taken from 17 newborn infants with Down's syndrome; 9 infants with Patau's syndrome; and 7 infants with Edwards' syndrome. For the control the brain of 21 newborn infants without defects of the CNS development (the death cause being analogous) was taken. In all the syndromes studied diversely directed but relatively specific shifts were revealed on the proteinograms. It was the albumin section which appeared to be the most sensitive to the chromosomal pathology: in cases of Down's and Patau's syndromes the protein content in it was reduced, whereas in cases of Edwards' syndrome it was increased. In the latter syndrome the relative amount of neuronines S-5 and S-6, and in Patau's syndrome the amount of neuronine S-6 were lowered, this lowering being statistically significantly. In all the trisomias a tendency to a diminution of the zone of the acidic neurospecific cerebral proteins was noted. This is, possibly, due to the lower level of the CNS functional activity in chromosomal pathologies.

  7. Plasmodium falciparum Bloom homologue, a nucleocytoplasmic protein, translocates in 3' to 5' direction and is essential for parasite growth.

    Science.gov (United States)

    Rahman, Farhana; Tarique, Mohammed; Tuteja, Renu

    2016-05-01

    Malaria caused by Plasmodium, particularly Plasmodium falciparum, is the most serious and widespread parasitic disease of humans. RecQ helicase family members are essential in homologous recombination-based error-free DNA repair processes in all domains of life. RecQ helicases present in each organism differ and several homologues have been identified in various multicellular organisms. These proteins are involved in various pathways of DNA metabolism by providing duplex unwinding function. Five members of RecQ family are present in Homo sapiens but P. falciparum contains only two members of this family. Here we report the detailed biochemical and functional characterization of the Bloom (Blm) homologue (PfBlm) from P. falciparum 3D7 strain. Purified PfBlm exhibits ATPase and 3' to 5' direction specific DNA helicase activity. The calculated average reaction rate of ATPase was ~13 pmol of ATP hydrolyzed/min/pmol of enzyme. The immunofluorescence assay results show that PfBlm is expressed in all the stages of intraerythrocytic development of the P. falciparum 3D7 strain. In some stages of development in addition to nucleus PfBlm also localizes in the cytoplasm. The gene disruption studies of PfBlm by dsRNA showed that it is required for the ex-vivo intraerythrocytic development of the parasite P. falciparum 3D7 strain. The dsRNA mediated inhibition of parasite growth suggests that a variety of pathways are affected resulting in curtailing of the parasite growth. This study will be helpful in unravelling the basic mechanism of DNA transaction in the malaria parasite and additionally it may provide leads to understand the parasite specific characteristics of this protein.

  8. Sneddon syndrome associated with Protein S deficiency.

    Science.gov (United States)

    Sayin, Refah; Bilgili, Serap Gunes; Karadag, Ayse Serap; Tombul, Temel

    2012-01-01

    Sneddon syndrome (SS) is rare, arterio-occlusive disorder characterized by generalized livedo racemosa of the skin and various central nervous symptoms due to occlusion of medium-sized arteries of unknown. Seizure, cognitive impairment, hypertension, and history of repetitive miscarriages are the other symptoms seen in this disease. Livedo racemosa involves persisting irreversible skin lesions red or blue in color with irregular margins. Usually, SS occurs in women of childbearing age. Protein S deficiency is an inherited or acquired disorder associated with an increased risk of thrombosis. We present a 33-year-old woman with SS with diffuse livedo racemosa, recurrent cerebrovascular diseases, migraine-type headache, sinus vein thrombosis, and protein S deficiency. Protein S deficiency and with Sneddon syndrome rarely encountered in the literature.

  9. Sneddon syndrome associated with Protein S deficiency

    Directory of Open Access Journals (Sweden)

    Refah Sayin

    2012-01-01

    Full Text Available Sneddon syndrome (SS is rare, arterio-occlusive disorder characterized by generalized livedo racemosa of the skin and various central nervous symptoms due to occlusion of medium-sized arteries of unknown. Seizure, cognitive impairment, hypertension, and history of repetitive miscarriages are the other symptoms seen in this disease. Livedo racemosa involves persisting irreversible skin lesions red or blue in color with irregular margins. Usually, SS occurs in women of childbearing age. Protein S deficiency is an inherited or acquired disorder associated with an increased risk of thrombosis. We present a 33-year-old woman with SS with diffuse livedo racemosa, recurrent cerebrovascular diseases, migraine-type headache, sinus vein thrombosis, and protein S deficiency. Protein S deficiency and with Sneddon syndrome rarely encountered in the literature.

  10. Harmful algal blooms

    Digital Repository Service at National Institute of Oceanography (India)

    Bhat, S.R.; PrabhaDevi; DeSouza, L.; Verlecar, X.N.; Naik, C.G.

    as harmful algal bloom. Bloom formation is a natural process and it enhances biological productivity, but turns worrisome when caused by toxic species, leading to massive fish mortalities and hazards to human health. Incidences of'red tide' are increasing...

  11. Blood Proteins Linked to Severity of Chronic Fatigue Syndrome

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_167505.html Blood Proteins Linked to Severity of Chronic Fatigue Syndrome Inflammation ... it to changes in 17 immune-system signaling proteins called cytokines. That suggests inflammation plays a part ...

  12. Update of the human secretoglobin (SCGB gene superfamily and an example of 'evolutionary bloom' of androgen-binding protein genes within the mouse Scgb gene superfamily

    Directory of Open Access Journals (Sweden)

    Jackson Brian C

    2011-10-01

    Full Text Available Abstract The secretoglobins (SCGBs comprise a family of small, secreted proteins found in animals exclusively of mammalian lineage. There are 11 human SCGB genes and five pseudogenes. Interestingly, mice have 68 Scgb genes, four of which are highly orthologous to human SCGB genes; the remainder represent an 'evolutionary bloom' and make up a large gene family represented by only six counterparts in humans. SCGBs are found in high concentrations in many mammalian secretions, including fluids of the lung, lacrimal gland, salivary gland, prostate and uterus. Whereas the biological activities of most individual SCGBs have not been fully characterised, what already has been discovered suggests that this family has an important role in the modulation of inflammation, tissue repair and tumorigenesis. In mice, the large Scgb1b and Scgb2b gene families encode the androgen-binding proteins, which have been shown to play a role in mate selection. Although much has been learned about SCGBs in recent years, clearly more research remains to be done to allow a better understanding of the roles of these proteins in human health and disease. Such information is predicted to reveal valuable novel drug targets for the treatment of inflammation, as well as designing biomarkers that might identify tissue damage or cancer.

  13. A case with Bloom Syndrome

    Directory of Open Access Journals (Sweden)

    Füsun Düzcan

    2008-10-01

    Full Text Available BS is a rare, autosomal recessive disorder characterized by telangiectasias, photosensitivity, growth deficiency of prenatal onset, immunodeficiency, increased susceptibility to malignancies and diabetes mellitus. There is an increased risk of developing neoplasia at early ages. Chromosomal fractures and an increase in sister chromatid exchanges are observed in BS that presents prominent genetic instability. A sixteen year old boy applied to our clinic with complaint of erythema on his face having existed since infancy. In physical examination of the patient in whom growth retardancy has been determined, a narrow, long face, prognatism, an erythematous telangiectatic blanchable patch involving malar areas, nose, forehead, and temples have been established. The patient whose sister chromatid exchange number was determined as 107/cell in cytogenetic analyse, was cited as BS together with his phenotypic findings. The patient has been taken into follow-up in terms of cancer risk and the family was genetically informed. (Turkderm 2008; 42: 94-6

  14. A genetic screen for components of the mammalian RNA interference pathway in Bloom-deficient mouse embryonic stem cells

    OpenAIRE

    2009-01-01

    Genetic screens performed in model organisms have helped identify key components of the RNA interference (RNAi) pathway. Recessive genetic screens have recently become feasible through the use of mouse embryonic stem (ES) cells that are Bloom's syndrome protein (Blm) deficient. Here, we developed and performed a recessive genetic screen to identify components of the mammalian RNAi pathway in Blm-deficient ES cells. Genome-wide mutagenesis using a retroviral gene trap strategy resulted in the ...

  15. Differential expression of ribosomal proteins in myelodysplastic syndromes.

    Science.gov (United States)

    Rinker, Elizabeth B; Dueber, Julie C; Qualtieri, Julianne; Tedesco, Jason; Erdogan, Begum; Bosompem, Amma; Kim, Annette S

    2016-02-01

    Aberrations of ribosomal biogenesis have been implicated in several congenital bone marrow failure syndromes, such as Diamond-Blackfan anaemia, Shwachman-Diamond syndrome and Dyskeratosis Congenita. Recent studies have identified haploinsufficiency of RPS14 in the acquired bone marrow disease isolated 5q minus syndrome, a subtype of myelodysplastic syndromes (MDS). However, the expression of various proteins comprising the ribosomal subunits and other proteins enzymatically involved in the synthesis of the ribosome has not been explored in non-5q minus MDS. Furthermore, differences in the effects of these expression alterations among myeloid, erythroid and megakaryocyte lineages have not been well elucidated. We examined the expression of several proteins related to ribosomal biogenesis in bone marrow biopsy specimens from patients with MDS (5q minus patients excluded) and controls with no known myeloid disease. Specifically, we found that there is overexpression of RPS24, DKC1 and SBDS in MDS. This overexpression is in contrast to the haploinsufficiency identified in the congenital bone marrow failure syndromes and in acquired 5q minus MDS. Potential mechanisms for these differences and aetiology for these findings in MDS are discussed.

  16. Allan Bloom's Quarrel with History.

    Science.gov (United States)

    Thompson, James

    1988-01-01

    Responds to Allan Bloom's "The Closing of the American Mind." Concludes that despite cranky comments about bourgeois culture, the focus of Bloom's attack is on historicism, which undercuts his nostalgic vision of a prosperous and just America. Condemns Bloom's exclusion of Blacks, Hispanics, and women from America's cultural heritage.…

  17. Allan Bloom's Quarrel with History.

    Science.gov (United States)

    Thompson, James

    1988-01-01

    Responds to Allan Bloom's "The Closing of the American Mind." Concludes that despite cranky comments about bourgeois culture, the focus of Bloom's attack is on historicism, which undercuts his nostalgic vision of a prosperous and just America. Condemns Bloom's exclusion of Blacks, Hispanics, and women from America's cultural heritage.…

  18. The distribution and impacts of harmful algal bloom species in eastern boundary upwelling systems

    Science.gov (United States)

    Trainer, V. L.; Pitcher, G. C.; Reguera, B.; Smayda, T. J.

    2010-04-01

    Comparison of harmful algal bloom (HAB) species in eastern boundary upwelling systems, specifically species composition, bloom densities, toxin concentrations and impacts are likely to contribute to understanding these phenomena. We identify and describe HABs in the California, Canary, Benguela and Humboldt Current systems, including those that can cause the poisoning syndromes in humans called paralytic shellfish poisoning (PSP), diarrhetic shellfish poisoning (DSP), and amnesic shellfish poisoning (ASP), as well as yessotoxins, ichthyotoxins, and high-biomass blooms resulting in hypoxia and anoxia. Such comparisons will allow identification of parameters, some unique to upwelling systems and others not, that contribute to the development of these harmful blooms.

  19. First Two Cases of Bloom Syndrome in Russia: Lack of Skin Manifestations in a BLM c.1642C>T (p.Q548X) Homozygote as a Likely Cause of Underdiagnosis.

    Science.gov (United States)

    Suspitsin, Evgeny N; Sibgatullina, Farida I; Lyazina, Lydia V; Imyanitov, Evgeny N

    2017-03-01

    Bloom syndrome (BS) is an exceptionally rare hereditary disease. Typical manifestations of BS usually include growth deficiency, a characteristic facial appearance, skin hypersensitivity to ultraviolet irradiation, and a strong predisposition to early-onset cancers. We have previously described a recurrent BLM c.1642C>T (p.Q548X) mutation, which is present in heterozygous state in 0.2-0.6% of individuals of Slavic origin. Despite the high occurrence of this founder allele, BS has not yet been described in patients of Slavic ethnicity. Here, we present 2 cases of BS, which were missed by standard genetic counseling and were eventually identified entirely due to chance. Our patients show the need for further investigations to confirm whether the atypical appearance of BS is indeed characteristic for biallelic carriers of the c.1642C>T (p.Q548X) allele and whether the absence of skin manifestations contributes to the underdiagnosis of the disease in Russia. Therefore, we suggest that all Slavic patients with only one single clinical feature of BS are to be screened for this allele and subjected to further analysis wherever appropriate. In addition to identifying new BS patients, this effort will help to clarify the frequency of "atypical BS" with incomplete phenotypic manifestations.

  20. 4-hydroxynonenal protein adducts: Key mediator in Rett syndrome oxinflammation.

    Science.gov (United States)

    Valacchi, Giuseppe; Pecorelli, Alessandra; Cervellati, Carlo; Hayek, Joussef

    2017-01-05

    In the last 15 years a strong correlation between oxidative stress (OxS) and Rett syndrome (RTT), a rare neurodevelopmental disorder known to be caused in 95% of the cases, by a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, has been well documented. Here, we revised, summarized and discussed the current knowledge on the role of lipid peroxidation byproducts, with special emphasis on 4-hydroxynonenal (4HNE), in RTT pathophysiology. The posttranslational modifications of proteins via 4HNE, known as 4HNE protein adducts (4NHE-PAs), causing detrimental effects on protein functions, appear to contribute to the clinical severity of the syndrome, since their levels increase significantly during the subsequent 4 clinical stages, reaching the maximum degree at stage 4, represented by a late motor deterioration. In addition, 4HNE-PA are only partially removed due to the compromised functionality of the proteasome activity, contributing therefore to the cellular damage in RTT. All this will lead to a characteristic subclinical inflammation, defined "OxInflammation", derived by a positive feedback loop between OxS byproducts and inflammatory mediators that in a long run further aggravates the clinical features of RTT patients. Therefore, in a pathology completely orphan of any therapy, aiming 4HNE as a therapeutic target could represent a coadjuvant treatment with some beneficial impact in these patients.‬‬‬.

  1. Virtual Screening and Molecular Docking Study of Bloom’s Syndrome Protein (BLM for Finding Potential Lead Drug Candidate

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Verma

    2014-06-01

    Full Text Available Increased levels of locus-specific mutations within the BLM result in development of Bloom Syndrome and patients are found to be immune deficient. HRDC domain amino acid Lys1270 is presumably to play role in mediating interactions with DNA. Single point mutation of Lys1270 (K1270V reduces the potency of Double Holliday junction (DHJ DNA unwinding so BLM lead to its functional loss. Quadruplex formation have role in immunoglobulin heavy chain switching and inhibiting RecQ helicases activity in-vitro in BLM. Variety of G-Quadruplex ligands are employed by molecular docking for arriving at lead compound identification. The scoring function of docking results describes protein-ligand interaction and it conjointly instructed that docking of ligand at mutational binding site shows some repressing function to make potential lead drug molecule. So as to know the elaborated purposeful functional mechanism of protein and to relate impact of mutation with function and activity; dock screening, hit identification and lead optimization facilitate in design of lead drug compound.

  2. Plasma protein oxidation and total antioxidant power in premenstrual syndrome

    Institute of Scientific and Technical Information of China (English)

    Eans Tara Tuladhar; Anjali Rao

    2010-01-01

    Objective:To explore whether oxidative stress has any role inpremenstrual syndrome (PMS). Methods: Female volunteers suffering from PMS , in the age group of 20-24 years were compared to their asymptomatic normomennorhoeic counterparts in follicular phase and late luteal phase for ferric reducing antioxidant power of plasma(FRAP), plasma protein thiols(PPT) and protein carbonyls(PPC) levels.Results:There was no significant change in FRAP and PPC levels in controls andPMS groups but PPT decreased significantly in luteal phase ofPMS (P< 0.05) when compared to follicular phase.Conclusions:Estrogen and progesterone, might be responsible for a healthy antioxidant profile inPMS. However, a marked decrease inPPT in luteal phase of PMS group may be due to pro-oxidant nature of estrogen-active in this phase of PMS leading to consumption of the sacrificial antioxidant-protein thiol.

  3. A New Bloom: Transforming Learning

    Science.gov (United States)

    Cochran, David; Conklin, Jack

    2007-01-01

    This article discusses a new design for the classic Bloom's Taxonomy developed by Anderson, L. W. & Krathwohl, D. (2001), which can be used to evaluate learners' technology-enhanced experience in more powerful and critical ways. The New Bloom's Taxonomy incorporates contemporary research on learning and human cognition into its model. The…

  4. Algal Bloom: Boon or Bane?

    Digital Repository Service at National Institute of Oceanography (India)

    LokaBharathi, P.A.

    productive regions. Sometimes land run off and other anthropogenic influences trigger intense bloom leading to anoxia that can affect fauna at higher levels When such algal blooms are toxic (ca 6% of 5000sps) they are referred to as HABS (harmful algal...

  5. Protein digestion and absorption in the blind loop syndrome.

    Science.gov (United States)

    Curtis, K J; Prizont, R; Kim, Y S

    1979-12-01

    Protein digestion and absorption was studied in rats with 6-week-old surgically constructed self-filling intestinal blind loops and steatorrhea, ie, blind-loop animals and controls were fed a 14C-labeled protein meal containing a nonabsorbable marker, 51CrCl3, and sacrificed 1 or 2 hr later. Intestinal contents were analyzed for 14C, 51Cr, protein, trypsin, and the products of digestion. At 1 hr, 14C absorption was greater in controls, but at 2 hr there was no difference in absorption between the two groups. Marker studies showed that blind-loop filling resulted in a delay of the progression of intestinal contents distally. Intraluminal trypsin and porteolysis were similar in the two groups. Endogenous protein was greater in the blind-loop animals. The early stages of the blind-loop syndrome may be characterized by delayed protein absorption secondary to blind-loop filling, which is compensated for by the distal gut resulting in an absence of overall protein malabsorption.

  6. Anti-thrombin III, Protein C, and Protein S deficiency in acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Dasnan Ismail

    2002-06-01

    Full Text Available The final most common pathway for the majority of coronary artery disease is occlusion of a coronary vessel. Under normal conditions, antithrombin III (AT III, protein C, and protein S as an active protein C cofactor, are natural anticoagulants (hemostatic control that balances procoagulant activity (thrombin antithrombin complex balance to prevent thrombosis. If the condition becomes unbalanced, natural anticoagulants and the procoagulants can lead to thrombosis. Thirty subjects with acute coronary syndrome (ACS were studied for the incidence of antithrombin III (AT III, protein C, and protein S deficiencies, and the result were compare to the control group. Among patients with ACS, the frequency of distribution of AT-III with activity < 75% were 23,3% (7 of 30, and only 6,7% ( 2 of 30 in control subject. No one of the 30 control subject have protein C activity deficient, in ACS with activity < 70% were 13,3% (4 of 30. Fifteen out of the 30 (50% control subjects had protein S activity deficiency, while protein S deficiency activity < 70% was found 73.3.% (22 out of 30. On linear regression, the deterministic coefficient of AT-III activity deficiency to the development ACS was 13,25 %, and the deterministic coefficient of protein C activity deficient to the development of ACS was 9,06 %. The cut-off point for AT-III without protein S deficiency expected to contribute to the development of vessel disease was 45%. On discriminant analysis, protein C activity deficiency posed a risk for ACS of 4,5 greater than non deficient subjects, and AT-III activity deficiency posed a risk for ACS of 3,5 times greater than non deficient subjects. On binary logistic regression, protein S activity acted only as a reinforcing factor of AT-III activity deficiency in the development of ACS. Protein C and AT III deficiency can trigger ACS, with determinant coefficients of 9,06% and 13,25% respectively. Low levels of protein C posed a greater risk of

  7. Study on The Mechanism of Effects of Lomefloxacin on Biological Properties of Bloom Syndrome Helicase%洛美沙星对Bloom综合征解旋酶生物学特性影响的机理研究

    Institute of Scientific and Technical Information of China (English)

    骆衡; 陈祥; 丁玫; 杨齐心; 许厚强

    2011-01-01

    Bloom syndrome helicase (BLM), an important member of RecQ family of DNA helicases, participates in cell metabolism including DNA repair, recombination, transcription, telomere maintenance, and plays key roles in maintaining chromosome stability. The mutation of BLM helicase may lead to Bloom syndrome. Bloom syndrome is a rare autosomal recessive genetic disorder characterized by genomic instability and the early development of many types of cancer. Lomefloxacin (LMX) may treat many diseases by inhibiting many enzymes in cells and interfering DNA metabolism through binding DNA, but the specific mechanism of action remains unclear. This study was conducted to determine the effects of LMX on DNA-binding activity, helicase activity, and ATPase activity of BLM642 ~1290 helicase by fluorescence polarized technology and free phosphorus assay technology; and the parameters of binding between LMX and helicase were studied by fluorescence and ultraviolet absorption spectroscopy, included binding constants, number of binding sites, the type of acting force, and binding distance. The results indicated that the reaction between the helicase and LMX was occurred spontaneously, there was one binding site between two molecules, the helicase and LMX might compound BLM-LMX complexes caused by electrostatic force and hydrophobic interaction force; moreover, the intrinsic fluorescence of the helicase was static quenched by LMX as a result of non-radioactive energy transfer. In this process, the helicase and ATPase activities were inhibited and DNA-binding activity of the helicase was promoted by LMX. The mechanism of effects of LMX on biological properties of BLM helicase may be included as below: LMX could inhibit the ATPase activity by allosteric mechanism and stabilize the conformation of the enzyme in low helicase activity state, destroy the coupling of ATP hydrolysis to unwinding, and inhibit the unwinding dsDNA by blocking helicase translocation. The reason that LMX could

  8. Associations among genotype, clinical phenotype, and intracellular localization of trafficking proteins in ARC syndrome

    NARCIS (Netherlands)

    Smith, Holly; Galmes, Romain; Gogolina, Ekaterina; Straatman-Iwanowska, Anna; Reay, Kim; Banushi, Blerida; Bruce, Christopher K.; Cullinane, Andrew R.; Romero, Rene; Chang, Richard; Ackermann, Oanez; Baumann, Clarisse; Cangul, Hakan; Celik, Fatma Cakmak; Aygun, Canan; Coward, Richard; Dionisi-Vici, Carlo; Sibbles, Barbara; Inward, Carol; Kim, Chong Ae; Klumperman, Judith; Knisely, A. S.; Watson, Steven P.; Gissen, Paul

    2012-01-01

    Arthrogryposisrenal dysfunctioncholestasis (ARC) syndrome is a rare autosomal recessive multisystem disorder caused by mutations in vacuolar protein sorting 33 homologue B (VPS33B) and VPS33B interacting protein, apicalbasolateral polarity regulator (VIPAR). Cardinal features of ARC include congenit

  9. Associations among genotype, clinical phenotype, and intracellular localization of trafficking proteins in ARC syndrome

    NARCIS (Netherlands)

    Smith, Holly; Galmes, Romain; Gogolina, Ekaterina; Straatman-Iwanowska, Anna; Reay, Kim; Banushi, Blerida; Bruce, Christopher K.; Cullinane, Andrew R.; Romero, Rene; Chang, Richard; Ackermann, Oanez; Baumann, Clarisse; Cangul, Hakan; Celik, Fatma Cakmak; Aygun, Canan; Coward, Richard; Dionisi-Vici, Carlo; Sibbles, Barbara; Inward, Carol; Kim, Chong Ae; Klumperman, Judith; Knisely, A. S.; Watson, Steven P.; Gissen, Paul

    2012-01-01

    Arthrogryposisrenal dysfunctioncholestasis (ARC) syndrome is a rare autosomal recessive multisystem disorder caused by mutations in vacuolar protein sorting 33 homologue B (VPS33B) and VPS33B interacting protein, apicalbasolateral polarity regulator (VIPAR). Cardinal features of ARC include congenit

  10. Kindler syndrome

    Directory of Open Access Journals (Sweden)

    Kaviarasan P

    2005-01-01

    Full Text Available Kindler syndrome is a rare autosomal recessive disorder associated with skin fragility. It is characterized by blistering in infancy, photosensitivity and progressive poikiloderma. The syndrome involves the skin and mucous membrane with radiological changes. The genetic defect has been identified on the short arm of chromosome 20. This report describes an 18-year-old patient with classical features like blistering and photosensitivity in childhood and the subsequent development of poikiloderma. The differential diagnosis of Kindler syndrome includes diseases like Bloom syndrome, Cockayne syndrome, dyskeratosis congenita, epidermolysis bullosa, Rothmund-Thomson syndrome and xeroderma pigmentosum. Our patient had classical cutaneous features of Kindler syndrome with phimosis as a complication.

  11. OSU MODIS FLH Bloom Product

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Two bloom products were developed for the Oregon coast based on the observed change between running 8-day composite chlorophyll-a (CHL) and fluorescence line-height...

  12. Further Verification of Bloom's Taxonomy

    Science.gov (United States)

    Roberts, Nancy

    1976-01-01

    Tests a curriculum designed to teach fifth and sixth grade students system dynamics thinking, an orientation that is congruent with the fourth and fifth levels of Bloom's "Taxonomy of Educational Objectives: Cognitive Domain".

  13. The Arid Melancholy-Netherton Syndrome With Protein Energy Malnutrition

    Science.gov (United States)

    Jain, Pramod Ajit; Pandey, Neha

    2016-01-01

    Netherton Syndrome (NS) is a rare autosomal recessive hereditary ichthyosiform disease with a classical triad comprising of an ichthyosiform dermatosis, hair shaft abnormalities and atopic diathesis. There is a mutation in a gene named Serine Protease Inhibitor Kazal type-5 (SPINK5); a new type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. Skin manifestations include, Ichthyosis Linearis Circumflexa (ILC), polycyclic and serpiginous, erythematous plaques with characteristic migratory, double-edged scale at the margins, or Congenital Ichthyosiform Erythroderma (CIE). Most of the patients have elevated immunoglobulin class E (IgE) and show atopic manifestations. Hair shaft abnormalities like pili torti and/or trichorrhexis nodosa, trichorrhexis invaginata, are seen. Here, we report a rare case of Netherton Syndrome having ILC and trichorrhexis nodosa with protein energy malnutrition in a five-year-old school going girl. She belonged to a poor socio-economic background and was worried about her physical appearance due to her skin lesions, causing psychosocial morbidity to her. PMID:27190931

  14. RPGR-containing protein complexes in syndromic and non-syndromic retinal degeneration due to ciliary dysfunction

    Indian Academy of Sciences (India)

    Carlos A. Murga-Zamalloa; Anand Swaroop; Hemant Khanna

    2009-12-01

    Dysfunction of primary cilia due to mutations in cilia-centrosomal proteins is associated with pleiotropic disorders. The primary (or sensory) cilium of photoreceptors mediates polarized trafficking of proteins for efficient phototransduction. Retinitis pigmentosa GTPase regulator (RPGR) is a cilia-centrosomal protein mutated in >70% of X-linked RP cases and 10%–20% of simplex RP males. Accumulating evidence indicates that RPGR may facilitate the orchestration of multiple ciliary protein complexes. Disruption of these complexes due to mutations in component proteins is an underlying cause of associated photoreceptor degeneration. Here, we highlight the recent developments in understanding the mechanism of cilia-dependent photoreceptor degeneration due to mutations in RPGR and RPGR-interacting proteins in severe genetic diseases, including retinitis pigmentosa, Leber congenital amaurosis (LCA), Joubert syndrome, and Senior–Loken syndrome, and explore the physiological relevance of photoreceptor ciliary protein complexes.

  15. Food protein-induced enterocolitis syndrome, from practice to theory.

    Science.gov (United States)

    Miceli Sopo, Stefano; Greco, Monica; Monaco, Serena; Tripodi, Salvatore; Calvani, Mauro

    2013-08-01

    Food protein-induced enterocolitis syndrome (FPIES) is an allergic disease, probably non-IgE-mediated, with expression predominantly in the GI tract. The most characteristic symptom is repeated, debilitating vomiting. It occurs 2-6 h after ingestion of culprit food and is usually accompanied by pallor and lethargy. There may be diarrhea, and in 10-20% of cases, severe hypotension. These symptoms resolve completely within a few hours. The food most frequently involved is cow's milk, followed by rice, but many other foods may be involved. The prognosis is generally good in a few years. In this review the authors try to cope, with the help of some case histories, with the practical clinical aspects of FPIES. The authors also try to provide a management approach based on current knowledge, and finally, to point out the aspects of FPIES that are still controversial.

  16. Uncoupling proteins, dietary fat and the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Warden Craig H

    2006-09-01

    Full Text Available Abstract There has been intense interest in defining the functions of UCP2 and UCP3 during the nine years since the cloning of these UCP1 homologues. Current data suggest that both UCP2 and UCP3 proteins share some features with UCP1, such as the ability to reduce mitochondrial membrane potential, but they also have distinctly different physiological roles. Human genetic studies consistently demonstrate the effect of UCP2 alleles on type-2 diabetes. Less clear is whether UCP2 alleles influence body weight or body mass index (BMI with many studies showing a positive effect while others do not. There is strong evidence that both UCP2 and UCP3 protect against mitochondrial oxidative damage by reducing the production of reactive oxygen species. The evidence that UCP2 protein is a negative regulator of insulin secretion by pancreatic β-cells is also strong: increased UCP2 decreases glucose stimulated insulin secretion ultimately leading to β-cell dysfunction. UCP2 is also neuroprotective, reducing oxidative stress in neurons. UCP3 may also transport fatty acids out of mitochondria thereby protecting the mitochondria from fatty acid anions or peroxides. Current data suggest that UCP2 plays a role in the metabolic syndrome through down-regulation of insulin secretion and development of type-2 diabetes. However, UCP2 may protect against atherosclerosis through reduction of oxidative stress and both UCP2 and UCP3 may protect against obesity. Thus, these UCP1 homologues may both contribute to and protect from the markers of the metabolic syndrome.

  17. Expression of Werner and Bloom syndrome genes is differentially regulated by in vitro HIV-1 infection of peripheral blood mononuclear cells.

    Science.gov (United States)

    Bordi, L; Amendola, A; Ciccosanti, F; Abbate, I; Camilloni, G; Capobianchi, M R

    2004-11-01

    In HIV infection, continuous immune activation leads to accelerated ageing of the adaptive immune system, similar to that observed in elderly people. We investigated the expression of WRN and BLM (genes involved in disorders characterized by premature ageing, genomic instability and cancer predisposition) in peripheral blood mononuclear cells (PBMC) activated in vitro with phytohaemagglutinin (PHA) and infected with different HIV-1 strains. The steady state levels of mRNA were analysed by reverse transcription-polymerase chain reaction (RT-PCR), and protein expression was assayed using immunocytochemistry and Western blot techniques. In uninfected PBMC, PHA stimulation induced an increase in BLM mRNA and protein expression, while WRN expression remained virtually unchanged. When PBMC were infected in vitro with a lymphotropic HIV-1 strain, the level of BLM mRNA showed a peak at 24 h of infection, followed by a decline to uninfected culture levels. A similar result failed to be seen using an R5-tropic HIV-1 strain. In accordance with mRNA expression, in HIV-infected cultures PBMC were stained more frequently and more intensely by a BLM-specific antibody as compared to uninfected cultures, staining peaking at 24. Conversely, WRN expression was not modulated by HIV-1. The proportion of cells showing BLM up-regulation, established by immunocytochemical staining, was much greater than the proportion of productively infected PBMC, as established by proviral DNA measurement. This result indicates that BLM up-regulation is probably a result of an indirect bystander cell effect. Activation of the BLM gene in infected PBMC suggests that premature ageing could be a further immunopathogenetic mechanism involved in HIV-induced immunodeficiency, and points to a possible new candidate target for innovative therapeutic intervention.

  18. Telomeric D-loops containing 8-oxo-2'-deoxyguanosine are preferred substrates for Werner and Bloom syndrome helicases and are bound by POT1.

    Science.gov (United States)

    Ghosh, Avik; Rossi, Marie L; Aulds, Jason; Croteau, Deborah; Bohr, Vilhelm A

    2009-11-06

    8-Oxo-2'-deoxyguanosine (8-oxodG) is one of the most important oxidative DNA lesions, and G-rich telomeric DNA is especially susceptible to oxidative DNA damage. RecQ helicases WRN and BLM and telomere-binding protein POT1 are thought to play roles in telomere maintenance. This study examines the ability of WRN, BLM, and RecQ5 to unwind and POT1 to bind telomeric D-loops containing 8-oxodG. The results demonstrate that WRN and BLM preferentially unwind telomeric D-loops containing 8-oxodG and that POT1 binds with higher affinity to telomeric D-loops with 8-oxodG but shows no preference for telomeric single-stranded DNA with 8-oxodG. We speculate that telomeric D-loops with 8-oxodG may have a greater tendency to form G-quadruplex DNA structures than telomeric DNA lacking 8-oxodG.

  19. C-Reactive Protein Levels in the Brugada Syndrome

    Directory of Open Access Journals (Sweden)

    Aimé Bonny

    2011-01-01

    Full Text Available Background. Inflammation in the Brugada syndrome (BrS and its clinical implication have been little studied. Aims. To assess the level of inflammation in BrS patients. Methods. All studied BrS patients underwent blood samples drawn for C-reactive protein (CRP levels at admission, prior to any invasive intervention. Patients with a previous ICD placement were controlled to exclude those with a recent (<14 days shock. We divided subjects into symptomatic (syncope or aborted sudden death and asymptomatic groups. In a multivariable analysis, we adjusted for significant variables (age, CRP ≥ 2 mg/L. Results. Fifty-four subjects were studied (mean age 45 ± 13 years, 49 (91% male. Twenty (37% were symptomatic. Baseline characteristics were similar in both groups. Mean CRP level was 1,4 ± 0,9 mg/L in asymptomatic and 2,4 ± 1,4 mg/L in symptomatic groups (P = .003. In the multivariate model, CRP concentrations ≥ 2 mg/L remained an independent marker for being symptomatic (P = .018; 95% CI: 1.3 to 19.3. Conclusion. Inflammation seems to be more active in symptomatic BrS. C-reactive protein concentrations ≥ 2 mg/L might be associated with the previous symptoms in BrS. The value of inflammation as a risk factor of arrhythmic events in BrS needs to be studied.

  20. Harmful Algal Blooms and Public Health.

    Science.gov (United States)

    Grattan, Lynn M; Holobaugh, Sailor; Morris, J Glenn

    2016-07-01

    The five most commonly recognized Harmful Algal Bloom related illnesses include Ciguatera poisoning, Paralytic Shellfish poisoning, Neurotoxin Shellfish poisoning, Diarrheic Shellfish Poisoning and Amnesic Shellfish poisoning. Although they are each the product of different toxins, toxin assemblages or HAB precursors these clinical syndromes have much in common. Exposure occurs through the consumption of fish or shellfish; routine clinical tests are not available for diagnosis; there is no known antidote for exposure; and the risk of these illnesses can negatively impact local fishing and tourism industries. Thus, illness prevention is of paramount importance to minimize human and public health risks. To accomplish this, close communication and collaboration is needed among HAB scientists, public health researchers and local, state and tribal health departments at academic, community outreach, and policy levels.

  1. Harmful Algal Blooms and Public Health

    Science.gov (United States)

    Grattan, Lynn M.; Holobaugh, Sailor; Morris, J. Glenn

    2015-01-01

    The five most commonly recognized Harmful Algal Bloom related illnesses include Ciguatera poisoning, Paralytic Shellfish poisoning, Neurotoxin Shellfish poisoning, Diarrheic Shellfish Poisoning and Amnesic Shellfish poisoning. Although they are each the product of different toxins, toxin assemblages or HAB precursors these clinical syndromes have much in common. Exposure occurs through the consumption of fish or shellfish; routine clinical tests are not available for diagnosis; there is no known antidote for exposure; and the risk of these illnesses can negatively impact local fishing and tourism industries. Thus, illness prevention is of paramount importance to minimize human and public health risks. To accomplish this, close communication and collaboration is needed among HAB scientists, public health researchers and local, state and tribal health departments at academic, community outreach, and policy levels. PMID:27616971

  2. Food protein induced enterocolitis syndrome caused by rice beverage.

    Science.gov (United States)

    Caminiti, Lucia; Salzano, Giuseppina; Crisafulli, Giuseppe; Porcaro, Federica; Pajno, Giovanni Battista

    2013-05-14

    Food protein-induced enterocolitis syndrome (FPIES) is an uncommon and potentially severe non IgE-mediated gastrointestinal food allergy. It is usually caused by cow's milk or soy proteins, but may also be triggered by ingestion of solid foods. The diagnosis is made on the basis of clinical history and symptoms. Management of acute phase requires fluid resuscitation and intravenous steroids administration, but avoidance of offending foods is the only effective therapeutic option.Infant with FPIES presented to our emergency department with vomiting, watery stools, hypothension and metabolic acidosis after ingestion of rice beverage. Intravenous fluids and steroids were administered with good clinical response. Subsequently, a double blind placebo control food challenge (DBPCFC) was performed using rice beverage and hydrolyzed formula (eHF) as placebo. The "rice based formula" induced emesis, diarrhoea and lethargy. Laboratory investigations reveal an increase of absolute count of neutrophils and the presence of faecal eosinophils. The patient was treated with both intravenous hydration and steroids. According to Powell criteria, oral food challenge was considered positive and diagnosis of FPIES induced by rice beverage was made. Patient was discharged at home with the indication to avoid rice and any rice beverage as well as to reintroduce hydrolyzed formula. A case of FPIES induced by rice beverage has never been reported. The present case clearly shows that also beverage containing rice proteins can be responsible of FPIES. For this reason, the use of rice beverage as cow's milk substitute for the treatment of non IgE-mediated food allergy should be avoided.

  3. Angelman syndrome protein UBE3A interacts with primary microcephaly protein ASPM, localizes to centrosomes and regulates chromosome segregation.

    Directory of Open Access Journals (Sweden)

    Pooja Singhmar

    Full Text Available Many proteins associated with the phenotype microcephaly have been localized to the centrosome or linked to it functionally. All the seven autosomal recessive primary microcephaly (MCPH proteins localize at the centrosome. Microcephalic osteodysplastic primordial dwarfism type II protein PCNT and Seckel syndrome (also characterized by severe microcephaly protein ATR are also centrosomal proteins. All of the above findings show the importance of centrosomal proteins as the key players in neurogenesis and brain development. However, the exact mechanism as to how the loss-of-function of these proteins leads to microcephaly remains to be elucidated. To gain insight into the function of the most commonly mutated MCPH gene ASPM, we used the yeast two-hybrid technique to screen a human fetal brain cDNA library with an ASPM bait. The analysis identified Angelman syndrome gene product UBE3A as an ASPM interactor. Like ASPM, UBE3A also localizes to the centrosome. The identification of UBE3A as an ASPM interactor is not surprising as more than 80% of Angelman syndrome patients have microcephaly. However, unlike in MCPH, microcephaly is postnatal in Angelman syndrome patients. Our results show that UBE3A is a cell cycle regulated protein and its level peaks in mitosis. The shRNA knockdown of UBE3A in HEK293 cells led to many mitotic abnormalities including chromosome missegregation, abnormal cytokinesis and apoptosis. Thus our study links Angelman syndrome protein UBE3A to ASPM, centrosome and mitosis for the first time. We suggest that a defective chromosome segregation mechanism is responsible for the development of microcephaly in Angelman syndrome.

  4. Angelman syndrome protein UBE3A interacts with primary microcephaly protein ASPM, localizes to centrosomes and regulates chromosome segregation.

    Science.gov (United States)

    Singhmar, Pooja; Kumar, Arun

    2011-01-01

    Many proteins associated with the phenotype microcephaly have been localized to the centrosome or linked to it functionally. All the seven autosomal recessive primary microcephaly (MCPH) proteins localize at the centrosome. Microcephalic osteodysplastic primordial dwarfism type II protein PCNT and Seckel syndrome (also characterized by severe microcephaly) protein ATR are also centrosomal proteins. All of the above findings show the importance of centrosomal proteins as the key players in neurogenesis and brain development. However, the exact mechanism as to how the loss-of-function of these proteins leads to microcephaly remains to be elucidated. To gain insight into the function of the most commonly mutated MCPH gene ASPM, we used the yeast two-hybrid technique to screen a human fetal brain cDNA library with an ASPM bait. The analysis identified Angelman syndrome gene product UBE3A as an ASPM interactor. Like ASPM, UBE3A also localizes to the centrosome. The identification of UBE3A as an ASPM interactor is not surprising as more than 80% of Angelman syndrome patients have microcephaly. However, unlike in MCPH, microcephaly is postnatal in Angelman syndrome patients. Our results show that UBE3A is a cell cycle regulated protein and its level peaks in mitosis. The shRNA knockdown of UBE3A in HEK293 cells led to many mitotic abnormalities including chromosome missegregation, abnormal cytokinesis and apoptosis. Thus our study links Angelman syndrome protein UBE3A to ASPM, centrosome and mitosis for the first time. We suggest that a defective chromosome segregation mechanism is responsible for the development of microcephaly in Angelman syndrome.

  5. TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome

    NARCIS (Netherlands)

    Lambacher, N.J.; Bruel, A.L.; Dam, T.J. van; Szymanska, K.; Slaats, G.G.; Kuhns, S.; McManus, G.J.; Kennedy, J.E.; Gaff, K.; Wu, K.M.; Lee, R. van der; Burglen, L.; Doummar, D.; Riviere, J.B.; Faivre, L.; Attie-Bitach, T.; Saunier, S.; Curd, A.; Peckham, M.; Giles, R.H.; Johnson, C.A.; Huynen, M.A.; Thauvin-Robinet, C.; Blacque, O.E.

    2016-01-01

    The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS). However, t

  6. TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome

    NARCIS (Netherlands)

    Lambacher, N.J.; Bruel, A.L.; Dam, T.J. van; Szymanska, K.; Slaats, G.G.; Kuhns, S.; McManus, G.J.; Kennedy, J.E.; Gaff, K.; Wu, K.M.; Lee, R. van der; Burglen, L.; Doummar, D.; Riviere, J.B.; Faivre, L.; Attie-Bitach, T.; Saunier, S.; Curd, A.; Peckham, M.; Giles, R.H.; Johnson, C.A.; Huynen, M.A.; Thauvin-Robinet, C.; Blacque, O.E.

    2016-01-01

    The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS). However,

  7. Bloom, Neatby, and the Lung Fishes.

    Science.gov (United States)

    Auer, John W.

    1991-01-01

    Discusses Allan Bloom's "The Closing of the American Mind" from a Canadian point of view, contending that Bloom's angry, irrational book on failures in U.S. society and higher education does not raise interesting or important ideas. Similarities and differences between Bloom and author Hilda Neatby are noted. (SM)

  8. Service discovery using Bloom filters

    NARCIS (Netherlands)

    Goering, P.T.H.; Heijenk, Gerhard J.; Lelieveldt, B.P.F.; Haverkort, Boudewijn R.H.M.; de Laat, C.T.A.M.; Heijnsdijk, J.W.J.

    A protocol to perform service discovery in adhoc networks is introduced in this paper. Attenuated Bloom filters are used to distribute services to nodes in the neighborhood and thus enable local service discovery. The protocol has been implemented in a discrete event simulator to investigate the

  9. Yellow nail syndrome: does protein leakage play a role?

    Science.gov (United States)

    D'Alessandro, A; Muzi, G; Monaco, A; Filiberto, S; Barboni, A; Abbritti, G

    2001-01-01

    Yellow nail syndrome is characterized by primary lymphoedema, recurrent pleural effusion and yellow discoloration of the nails. Although mechanical lymphatic obstruction is assumed to be the underlying pathology, it cannot explain the common finding of high albumin concentration in the pleural space. This paper describes a case of yellow nail syndrome presenting with the classical triad of lymphoedema, recurrent pleural effusion and yellow discoloration of the nails, associated with persistent hypoalbuminaemia and increased enteric loss of albumin. Based on the findings in this case and those in the literature, it is speculated that increased microvascular permeability may contribute to the pathogenesis of this syndrome.

  10. Blooming Seas West of Ireland

    Science.gov (United States)

    2007-01-01

    For several weeks in May and early June, daily satellite images of the North Atlantic Ocean west of Ireland have captured partial glimpses of luxuriant blooms of microscopic marine plants between patches of clouds. On June 4, 2007, the skies over the ocean cleared, displaying the sea's spring bloom in brilliant color. A bright blue bloom stretches north from the Mouth of the River Shannon and tapers off like a plume of blue smoke north of Clare Island. (In the large image, a second bloom is visible to the north, wrapping around County Donegal, on the island's northwestern tip.) The image was captured by the Moderate Resolution Imaging Spectroradiometer (MODIS) on NASA's Terra satellite. Cold, nutrient-stocked water often wells up to the surface from the deeper ocean along coastal shelves and at the edges of ocean currents. When it does, it delivers a boost of nutrients that fuel large blooms of single-celled plants collectively known as phytoplankton. The plants are the foundation of the marine food web, and their proliferation in this area of the North Atlantic explains why the waters of western Ireland support myriad fisheries and populations of large mammals like seals, whales, and dolphins. Like plants on land, phytoplankton make their food through photosynthesis, harnessing sunlight for energy using chlorophyll and other light-capturing pigments. The pigments change the way light reflects off the surface water, appearing as colorful swirls of turquoise and green against the darker blue of the ocean. Though individually tiny, collectively these plants play a big role in Earth's carbon and climate cycles; worldwide, they remove about as much carbon dioxide from the atmosphere during photosynthesis as land plants do. Satellites are the only way to map the occurrence of phytoplankton blooms across the global oceans on a regular basis. That kind of information is important not only to scientists who model carbon and climate, but also to biologists and fisheries

  11. Association between C-reactive protein and features of the metabolic syndrome

    DEFF Research Database (Denmark)

    Fröhlich, M; Imhof, A; Berg, Gabriele

    2000-01-01

    OBJECTIVE: To assess the association of circulating levels of C-reactive protein, a sensitive systemic marker of inflammation, with different components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: Total cholesterol (TC), HDL cholesterol, triglycerides, uric acid, BMI , and prevalence...... concentrations in subjects grouped according to the presence of 0-1, 2-3, and > or =4 features of the metabolic syndrome were 1.11, 1.27, and 2.16 mg/l, respectively, with a statistically highly significant trend (P metabolic syndrome...

  12. Lovastatin Corrects Excess Protein Synthesis and Prevents Epileptogenesis in a Mouse Model of Fragile X Syndrome

    OpenAIRE

    Chuang, Shih-Chieh; Chubykin, Alexander A.; Sidorov, Michael; Bianchi, Riccardo; Wong, Robert K.S.; Osterweil, Emily; Bear, Mark; Chubykin, Alexander A.

    2013-01-01

    Many neuropsychiatric symptoms of fragile X syndrome (FXS) are believed to be a consequence of altered regulation of protein synthesis at synapses. We discovered that lovastatin, a drug that is widely prescribed for the treatment of high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent one of the robust functional consequences of increased protein synthesis in FXS, epileptogenesis. These data suggest that lovastatin is potentially disease...

  13. Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syndrome

    OpenAIRE

    Osterweil, Emily K.; Chuang, Shih-Chieh; Chubykin, Alexander A.; Sidorov, Michael; Bianchi, Riccardo; Wong, Robert K. S.; Bear, Mark F.

    2013-01-01

    Many neuropsychiatric symptoms of fragile X syndrome (FXS) are believed to be a consequence of altered regulation of protein synthesis at synapses. We discovered that lovastatin, a drug that is widely prescribed for treatment of high cholesterol, can correct excess hippocampal protein synthesis in themouse model of FXS and can prevent one of the robust functional consequences of increased protein synthesis in FXS, epileptogenesis. These data suggest that lovastatin is potentially disease modi...

  14. MERUNUT PEMAHAMAN TAKSONOMI BLOOM: SUATU KONTEMPLASI FILOSOFIS

    OpenAIRE

    Dominikus Tulasi

    2010-01-01

    This article would like to share the use of Bloom's taxonomy as a cognitive framework for teaching-learning process to undertake the way student-centered learning. Related to the curriculum based competence in excellent education, the abstract cognitive in applying Blooms taxonomy is so called scaffolding. We know the taxonomy Bloom is a six-level classification system that uses observed student behavior to infer and absorb the level of cognitive achievement domain. This article surveys think...

  15. Budd-Chiari syndrome during nephrotic relapse in a patient with resistance to activated protein C clotting inhibitor.

    Science.gov (United States)

    Gambaro, G; Patrassi, G; Pittarello, F; Nardellotto, A; Checchetto, S; D'Angelo, A

    1998-10-01

    It has long been known that patients with nephrotic syndrome have a hypercoagulable state, which explains the association between nephrotic syndrome, renal vein thrombosis, and thromboembolism. However, the Budd-Chiari syndrome has never been reported in nephrotic patients. This is the first report of such an association that, most likely, depended on a primary resistance to activated protein C.

  16. Massive phytoplankton blooms under Arctic sea ice.

    Science.gov (United States)

    Arrigo, Kevin R; Perovich, Donald K; Pickart, Robert S; Brown, Zachary W; van Dijken, Gert L; Lowry, Kate E; Mills, Matthew M; Palmer, Molly A; Balch, William M; Bahr, Frank; Bates, Nicholas R; Benitez-Nelson, Claudia; Bowler, Bruce; Brownlee, Emily; Ehn, Jens K; Frey, Karen E; Garley, Rebecca; Laney, Samuel R; Lubelczyk, Laura; Mathis, Jeremy; Matsuoka, Atsushi; Mitchell, B Greg; Moore, G W K; Ortega-Retuerta, Eva; Pal, Sharmila; Polashenski, Chris M; Reynolds, Rick A; Schieber, Brian; Sosik, Heidi M; Stephens, Michael; Swift, James H

    2012-06-15

    Phytoplankton blooms over Arctic Ocean continental shelves are thought to be restricted to waters free of sea ice. Here, we document a massive phytoplankton bloom beneath fully consolidated pack ice far from the ice edge in the Chukchi Sea, where light transmission has increased in recent decades because of thinning ice cover and proliferation of melt ponds. The bloom was characterized by high diatom biomass and rates of growth and primary production. Evidence suggests that under-ice phytoplankton blooms may be more widespread over nutrient-rich Arctic continental shelves and that satellite-based estimates of annual primary production in these waters may be underestimated by up to 10-fold.

  17. Bone morphogenetic proteins and the polycystic ovary syndrome

    NARCIS (Netherlands)

    E.L.A.F. van Houten (Leonie); J.S.E. Laven (Joop); Y.V. Louwers (Yvonne); A. McLuskey; A.P.N. Themmen (Axel); J.A. Visser (Jenny)

    2013-01-01

    textabstractBackground: Polycystic Ovary Syndrome (PCOS) is defined by two out of the following three criteria being met: oligo- or anovulation, hyperandrogenism, and polycystic ovaries. Affected women are often obese and insulin resistant. Although the etiology is still unknown, members of the Tran

  18. Algae Bloom in a Lake

    Directory of Open Access Journals (Sweden)

    David Sanabria

    2008-01-01

    Full Text Available The objective of this paper is to determine the likelihood of an algae bloom in a particular lake located in upstate New York. The growth of algae in this lake is caused by a high concentration of phosphorous that diffuses to the surface of the lake. Our calculations, based on Fick's Law, are used to create a mathematical model of the driving force of diffusion for phosphorous. Empirical observations are also used to predict whether the concentration of phosphorous will diffuse to the surface of this lake within a specified time and under specified conditions.

  19. BOR-syndrome-associated Eya1 mutations lead to enhanced proteasomal degradation of Eya1 protein.

    Directory of Open Access Journals (Sweden)

    Amna Musharraf

    Full Text Available Mutations in the human EYA1 gene have been associated with several human diseases including branchio-oto (BO and branchio-oto-renal (BOR syndrome, as well as congenital cataracts and ocular anterior segment anomalies. BOR patients suffer from severe malformations of the ears, branchial arches and kidneys. The phenotype of Eya1-heterozygous mice resembles the symptoms of human patients suffering from BOR syndrome. The Eya1 gene encodes a multifunctional protein that acts as a protein tyrosine phosphatase and a transcriptional coactivator. It has been shown that Eya1 interacts with Six transcription factors, which are also required for nuclear translocation of the Eya1 protein. We investigated the effects of seven disease-causing Eya1 missense mutations on Eya1 protein function, in particular cellular localization, ability to interact with Six proteins, and protein stability. We show here that the BOR-associated Eya1 missense mutations S454P, L472R, and L550P lead to enhanced proteasomal degradation of the Eya1 protein in mammalian cells. Moreover, Six proteins lead to a significant stabilization of Eya1, which is caused by Six-mediated protection from proteasomal degradation. In case of the mutant L550P, loss of interaction with Six proteins leads to rapid protein degradation. Our observations suggest that protein destabilization constitutes a novel disease causing mechanism for Eya1.

  20. Impact of weight loss and maintenance with ad libitum diets varying in protein and glycemic index content on metabolic syndrome

    DEFF Research Database (Denmark)

    Papadaki, Angeliki; Linardakis, Manolis; Plada, Maria

    2014-01-01

    We investigated the effects of weight loss and maintenance with diets that varied with regard to protein content and glycemic index (GI) on metabolic syndrome (MetSyn) status.......We investigated the effects of weight loss and maintenance with diets that varied with regard to protein content and glycemic index (GI) on metabolic syndrome (MetSyn) status....

  1. Algal blooms and Membrane Based Desalination Technology

    NARCIS (Netherlands)

    Villacorte, L.O.

    2014-01-01

    Seawater desalination is rapidly growing in terms of installed capacity (~80 million m3/day in 2013), plant size and global application. An emerging threat to this technology is the seasonal proliferation of microscopic algae in seawater known as algal blooms. Such blooms have caused operational pro

  2. Summer heatwaves promote blooms of harmful cyanobacteria

    NARCIS (Netherlands)

    Joehnk, K.D; Huisman, J.; Sharples, J.; Sommeijer, B.P.; Visser, P.M.; Stroom, J.M.

    2008-01-01

    Dense surface blooms of toxic cyanobacteria in eutrophic lakes may lead to mass mortalities of fish and birds, and provide a serious health threat for cattle, pets, and humans. It has been argued that global warming may increase the incidence of harmful algal blooms. Here, we report on a lake experi

  3. Algal blooms and Membrane Based Desalination Technology

    NARCIS (Netherlands)

    Villacorte, L.O.

    2014-01-01

    Seawater desalination is rapidly growing in terms of installed capacity (~80 million m3/day in 2013), plant size and global application. An emerging threat to this technology is the seasonal proliferation of microscopic algae in seawater known as algal blooms. Such blooms have caused operational pro

  4. Bloom's Idiosyncratic History of the University.

    Science.gov (United States)

    Lawler, Peter Augustine

    1989-01-01

    Analyzes "The Idiosyncratic History of the University," a chapter in Allan Bloom's "The Closing of the American Mind". Focuses on Bloom's history of the university as explained through Socrates' philosophy. Concentrates on the role of philosophers in society past and present. Discusses the Enlightenment, Existentialism,…

  5. Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome

    DEFF Research Database (Denmark)

    Ü Basmanav, F Buket; Cau, Laura; Tafazzoli, Aylar

    2016-01-01

    Uncombable hair syndrome (UHS), also known as "spun glass hair syndrome," "pili trianguli et canaliculi," or "cheveux incoiffables" is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant...... in the majority of UHS case subjects. The two enzymes PADI3 and TGM3, responsible for posttranslational protein modifications, and their target structural protein TCHH are all involved in hair shaft formation. Elucidation of the molecular outcomes of the disease-causing mutations by cell culture experiments...... and tridimensional protein models demonstrated clear differences in the structural organization and activity of mutant and wild-type proteins. Scanning electron microscopy observations revealed morphological alterations in hair coat of Padi3 knockout mice. All together, these findings elucidate the molecular genetic...

  6. Metabolic syndrome, insulin resistance, fibrinogen, homocysteine, leptin, and C-reactive protein in obese patients with obstructive sleep apnea syndrome

    Directory of Open Access Journals (Sweden)

    Basoglu Ozen

    2011-01-01

    Full Text Available Objective: The prevalence of obstructive sleep apnea syndrome (OSAS and metabolic syndrome is increasing worldwide, in part linked to epidemic of obesity. The purposes of this study were to establish the rate of metabolic syndrome and to compare fibrinogen, homocysteine, high-sensitivity C-reactive protein (hsCRP, leptin levels, and homeostasis model assessment insulin resistance (HOMA-IR in the obese patients with and without OSAS. Methods: The study population included 36 consecutive obese patients with OSAS (23 males; mean age, 50.0 ±19.7 years, and 34 obese patients without OSAS (17 males; mean age, 49.7±11.1 years were enrolled as control group. Metabolic syndrome was investigated; fibrinogen, homocysteine, CRP, and leptin levels were measured, and IR was assessed. Results: Metabolic syndrome was found in 17 (47.2% obese OSAS patients, whereas only 29.4% of obese subjects had metabolic syndrome (P > 0.05. Obese patients with OSAS had significantly higher mean levels of triglyceride (P< 0.001, total-cholesterol ( P = 0.003, low-density lipoprotein-cholesterol ( P = 0.001, fasting glucose ( P = 0.01, HOMA-IR ( P<0.001, thyroid-stimulating hormone ( P = 0.03, fibrinogen ( P < 0.003, hsCRP ( P <0.001, and leptin ( P = 0.03 than control group . Besides, leptin level was positively correlated with waist ( r = 0.512, P = 0.03 and neck circumferences ( r = 0.547, P = 0.03, and fasting glucose (r = 0.471, P = 0.04 in OSAS patients, but not in obese subjects. Conclusion: This study demonstrated that obese OSAS patients may have an increased rate of metabolic syndrome and higher levels of serum lipids, fasting glucose, IR, leptin, fibrinogen, and hsCRP than obese subjects without sleep apnea. Thus, clinicians should be encouraged to systematically evaluate the presence of metabolic abnormalities in OSAS and vice versa.

  7. Amyloid-related biomarkers and axonal damage proteins in parkinsonian syndromes

    DEFF Research Database (Denmark)

    Bech, Sara; Hjermind, Lena E; Salvesen, Lisette;

    2012-01-01

    Clinical differentiation between parkinsonian syndromes (PS) remains a challenge despite well-established clinical diagnostic criteria. Specific diagnostic biomarkers have yet to be identified, though in recent years, studies have been published on the aid of certain brain related proteins (BRP...

  8. Three functionally diverged major White Spot Syndrome Virus structural proteins evolved by gene duplication

    NARCIS (Netherlands)

    Hulten, van M.C.W.; Goldbach, R.W.; Vlak, J.M.

    2000-01-01

    White spot syndrome virus (WSSV) is an invertebrate virus causing considerable mortality in penaeid shrimp. The oval-to-bacilliform shaped virions, isolated from infected Penaeus monodon, contain four major proteins: VP28, VP26, VP24 and VP19 (28, 26, 24 and 19 kDa, respectively). VP26 and VP24 are

  9. Morvan's syndrome with anti contactin associated protein like 2 – voltage gated potassium channel antibody presenting with syndrome of inappropriate antidiuretic hormone secretion

    Directory of Open Access Journals (Sweden)

    Anjani Kumar Sharma

    2016-01-01

    Full Text Available Morvan's syndrome is a rare autoimmune disorder characterized by triad of peripheral nerve hyperexcitability, autonomic dysfunction, and central nervous system symptoms. Antibodies against contactin-associated protein-like 2 (CASPR2, a subtype of voltage-gated potassium channel (VGKC complex, are found in a significant proportion of patients with Morvan's syndrome and are thought to play a key role in peripheral as well as central clinical manifestations. We report a patient of Morvan's syndrome with positive CASPR2–anti-VGKC antibody having syndrome of inappropriate antidiuretic hormone as a cause of persistent hyponatremia.

  10. Morvan's syndrome with anti contactin associated protein like 2 – voltage gated potassium channel antibody presenting with syndrome of inappropriate antidiuretic hormone secretion

    Science.gov (United States)

    Sharma, Anjani Kumar; Kaur, Manminder; Paul, Madhuparna

    2016-01-01

    Morvan's syndrome is a rare autoimmune disorder characterized by triad of peripheral nerve hyperexcitability, autonomic dysfunction, and central nervous system symptoms. Antibodies against contactin-associated protein-like 2 (CASPR2), a subtype of voltage-gated potassium channel (VGKC) complex, are found in a significant proportion of patients with Morvan's syndrome and are thought to play a key role in peripheral as well as central clinical manifestations. We report a patient of Morvan's syndrome with positive CASPR2–anti-VGKC antibody having syndrome of inappropriate antidiuretic hormone as a cause of persistent hyponatremia. PMID:27695240

  11. The Raine syndrome protein FAM20C is a Golgi kinase that phosphorylates bio-mineralization proteins.

    Directory of Open Access Journals (Sweden)

    Hiroyuki O Ishikawa

    Full Text Available Raine syndrome is caused by mutations in FAM20C, which had been reported to encode a secreted component of bone and teeth. We found that FAM20C encodes a Golgi-localized protein kinase, distantly related to the Golgi-localized kinase Four-jointed. Drosophila also encode a Golgi-localized protein kinase closely related to FAM20C. We show that FAM20C can phosphorylate secreted phosphoproteins, including both Casein and members of the SIBLING protein family, which modulate biomineralization, and we find that FAM20C phosphorylates a biologically active peptide at amino acids essential for inhibition of biomineralization. We also identify autophosphorylation of FAM20C, and characterize parameters of FAM20C's kinase activity, including its Km, pH and cation dependence, and substrate specificity. The biochemical properties of FAM20C match those of an enzymatic activity known as Golgi casein kinase. Introduction of point mutations identified in Raine syndrome patients into recombinant FAM20C impairs its normal localization and kinase activity. Our results identify FAM20C as a kinase for secreted phosphoproteins and establish a biochemical basis for Raine syndrome.

  12. Proteomic analysis of differentially expressed proteins in Fenneropenaeus chinensis hemocytes upon white spot syndrome virus infection.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available To elucidate molecular responses of shrimp hemocytes to white spot syndrome virus (WSSV infection, two-dimensional gel electrophoresis was applied to investigate differentially expressed proteins in hemocytes of Chinese shrimp (Fenneropenaeus chinensis at 24 h post infection (hpi. Approximately 580 protein spots were detected in hemocytes of healthy and WSSV-infected shrimps. Quantitative intensity analysis revealed 26 protein spots were significantly up-regulated, and 19 spots were significantly down-regulated. By mass spectrometry, small ubiquitin-like modifier (SUMO 1, cytosolic MnSOD, triosephosphate isomerase, tubulin alpha-1 chain, microtubule-actin cross-linking factor 1, nuclear receptor E75 protein, vacuolar ATP synthase subunit B L form, inositol 1,4,5-trisphosphate receptor, arginine kinase, etc., amounting to 33 differentially modulated proteins were identified successfully. According to Gene Ontology annotation, the identified proteins were classified into nine categories, consisting of immune related proteins, stimulus response proteins, proteins involved in glucose metabolic process, cytoskeleton proteins, DNA or protein binding proteins, proteins involved in steroid hormone mediated signal pathway, ATP synthases, proteins involved in transmembrane transport and ungrouped proteins. Meanwhile, the expression profiles of three up-regulated proteins (SUMO, heat shock protein 70, and arginine kinase and one down-regulated protein (prophenoloxidase were further analyzed by real-time RT-PCR at the transcription level after WSSV infection. The results showed that SUMO and heat shock protein 70 were significantly up-regulated at each sampling time point, while arginine kinase was significantly up-regulated at 12 and 24 hpi. In contrast, prophenoloxidase was significantly down-regulated at each sampling time point. The results of this work provided preliminary data on proteins in shrimp hemocytes involved in WSSV infection.

  13. A role for Alstrom syndrome protein, alms1, in kidney ciliogenesis and cellular quiescence.

    Directory of Open Access Journals (Sweden)

    Guochun Li

    2007-01-01

    Full Text Available Premature truncation alleles in the ALMS1 gene are a frequent cause of human Alström syndrome. Alström syndrome is a rare disorder characterized by early obesity and sensory impairment, symptoms shared with other genetic diseases affecting proteins of the primary cilium. ALMS1 localizes to centrosomes and ciliary basal bodies, but truncation mutations in Alms1/ALMS1 do not preclude formation of cilia. Here, we show that in vitro knockdown of Alms1 in mice causes stunted cilia on kidney epithelial cells and prevents these cells from increasing calcium influx in response to mechanical stimuli. The stunted-cilium phenotype can be rescued with a 5' fragment of the Alms1 cDNA, which resembles disease-associated alleles. In a mouse model of Alström syndrome, Alms1 protein can be stably expressed from the mutant allele and is required for cilia formation in primary cells. Aged mice developed specific loss of cilia from the kidney proximal tubules, which is associated with foci of apoptosis or proliferation. As renal failure is a common cause of mortality in Alström syndrome patients, we conclude that this disease should be considered as a further example of the class of renal ciliopathies: wild-type or mutant alleles of the Alström syndrome gene can support normal kidney ciliogenesis in vitro and in vivo, but mutant alleles are associated with age-dependent loss of kidney primary cilia.

  14. Study of Plasma Malondialdehyde, Troponin I and C - Reactive protein in Acute Coronary Syndromes Patients

    Directory of Open Access Journals (Sweden)

    S. Shams

    2006-04-01

    Full Text Available Introduction & Objective: Ischemic injury of endothelium is associated with prostaglandin synthesis and platelet adhesion and aggregation, which may be associated with the release of aldehydes such as malondialdehyde (MDA. C-reactive protein and cardiac troponin I have been proposed as diagnostic markers of acute coronary syndromes. In this study, we compared the usefulness of plasma MDA as a marker of acute coronary syndromes with that of C-reactive protein and troponin I.Material & Methods: The study population contained 50 patients with unstable angina and 50 patients with acute myocardial infarction admitted to the hearth department of the Ekbatan Hospital of Hamadan. The subjects were matched according to age and sex. Total cholesterol, LDL and HDL cholesterol, triglycerides, plasma MDA, troponin I and C-reactive protein levels were determined in all patients. Results: Results showed that the plasma MDA levels were significantly higher in patients with acute myocardial infarction than in individuals with unstable angina (P<0.001 and were associated with increased levels of troponin I and C-reactive protein (P<0.001.Conclusion: The combination of the plasma MDA levels, which reflect endothelial injury, and troponin I and C-reactive protein levels may allow better discrimination in acute coronary syndromes patients.

  15. Posttranslational Protein Modification in the Salivary Glands of Sjögren's Syndrome Patients.

    Science.gov (United States)

    Herrera-Esparza, Rafael; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Badillo-Soto, Martha Adriana; Torres-Del-Muro, Felipe; Bollain-Y-Goytia, Juan José; Pacheco-Tovar, Deyanira; Avalos-Díaz, Esperanza

    2013-01-01

    The present study investigated posttranslational reactions in the salivary glands of patients with Sjögren's syndrome. We analysed the biopsies of primary Sjögren's patients using immunohistochemistry and a tag-purified anticyclic citrullinated protein (CCP) antibody to detect citrullinated peptides, and the presence of peptidylarginine deiminase 2 (PAD2) was assessed simultaneously. The present work demonstrated the weak presence of the PAD2 enzyme in some normal salivary glands, although PAD2 expression was increased considerably in Sjögren's patients. The presence of citrullinated proteins was also detected in the salivary tissues of Sjögren's patients, which strongly supports the in situ posttranslational modification of proteins in this setting. Furthermore, the mutual expression of CCP and PAD2 suggests that this posttranslational modification is enzyme dependent. In conclusion, patients with Sjögren's syndrome expressed the catalytic machinery to produce posttranslational reactions that may result in autoantigen triggering.

  16. Assessment of microcystis bloom toxicity associated with wildlife mortality in the Kruger National Park, South Africa.

    Science.gov (United States)

    Masango, Mxolisi G; Myburgh, Jan G; Labuschagne, Leonie; Govender, Danny; Bengis, Roy G; Naicker, Dharmarai

    2010-01-01

    Based on previous necropsy results, Microcystis blooms in constructed water impoundments in the Kruger National Park (KNP) have been identified as a cause of wildlife mortality. In response to wildlife mortality during 2007, water samples, containing algal bloom material, were collected during February 2007 and July 2007 from four dams (Nhlanganzwani, Mpanamana, Makhohlola, and Sunset) in the southeastern part of the KNP as part of the follow-up investigation. The toxicity of the Microcystis blooms was determined using the enzyme-linked immunosorbent assay (ELISA), protein phosphatase inhibition (PPI) assay, mouse bioassay, and African sharptooth catfish (Clarias gariepinus) primary hepatocytes. Both the ELISA and PPI assays indicated that the water sample collected during February 2007 from the Nhlanganzwani Dam, and samples collected from the Nhlanganzwani and Sunset dams in June 2007, were toxic. These dams, exhibiting the toxic Microcystis blooms, were also associated with the wildlife mortality. Mice injected intraperitoneally with water samples from Nhlanganzwani Dam (February 2007) induced hepatotoxicity and mortality within 1 hr. Primary hepatocytes from the sharptooth catfish exposed to samples from these dams gave similar results. This laboratory investigation and results strongly incriminate the toxic Microcystis blooms as the cause of the wildlife mortality. Eutrophication and bloom formation appear to have been the consequence of the high numbers of hippopotami (Hippopotamus amphibius) in specific dams.

  17. The effects of GH and hormone replacement therapy on serum concentrations of mannan-binding lectin, surfactant protein D and vitamin D binding protein in Turner syndrome

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Leth-Larsen, Rikke; Lauridsen, Anna Lis

    2004-01-01

    function. In the present study we examined whether GH or hormone replacement therapy (HRT) in Turner syndrome (TS) influence the serum concentrations of MBL and two other proteins partaking in the innate immune defence, surfactant protein D (SP-D) and vitamin D binding protein (DBP). DESIGN: Study 1...

  18. Unusual phenotype of glucose transport protein type 1 deficiency syndrome: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Annio Posar

    2014-01-01

    Full Text Available The glucose transport protein type 1 (GLUT1 deficit causes a chronic brain energy failure. The classic phenotype of GLUT1 deficiency syndrome is characterized by: Mild to severe motor delay and mental retardation; infantile-onset epilepsy; head growth deceleration; movement disorders (ataxia, dystonia, spasticity; and non-epileptic paroxysmal events (intermittent ataxia, periodic confusion, recurrent headaches. During last years the classic phenotype of this syndrome, as originally reported, has expanded. We report the atypical phenotype of a boy with GLUT1 deficiency syndrome, characterized by mild mental retardation and drug-resistant absence seizures with onset at the age of 6 years, without movement disorders nor decrease of head circumference. A prompt diagnosis of this disorder is mandatory since the ketogenic diet might represent an effective treatment.

  19. The Role of Maternal Dietary Proteins in Development of Metabolic Syndrome in Offspring

    Directory of Open Access Journals (Sweden)

    Alireza Jahan-Mihan

    2015-11-01

    Full Text Available The prevalence of metabolic syndrome and obesity has been increasing. Pre-natal environment has been suggested as a factor influencing the risk of metabolic syndrome in adulthood. Both observational and experimental studies showed that maternal diet is a major modifier of the development of regulatory systems in the offspring in utero and post-natally. Both protein content and source in maternal diet influence pre- and early post-natal development. High and low protein dams’ diets have detrimental effect on body weight, blood pressure191 and metabolic and intake regulatory systems in the offspring. Moreover, the role of the source of protein in a nutritionally adequate maternal diet in programming of food intake regulatory system, body weight, glucose metabolism and blood pressure in offspring is studied. However, underlying mechanisms are still elusive. The purpose of this review is to examine the current literature related to the role of proteins in maternal diets in development of characteristics of the metabolic syndrome in offspring.

  20. Increased fasting plasma acylation-stimulating protein concentrations in nephrotic syndrome.

    Science.gov (United States)

    Ozata, Metin; Oktenli, Cagatay; Gulec, Mustafa; Ozgurtas, Taner; Bulucu, Fatih; Caglar, Kayser; Bingol, Necati; Vural, Abdulgaffar; Ozdemir, I Caglayan

    2002-02-01

    Acylation-stimulating protein (ASP) is an adipocyte-derived protein that has recently been suggested to play an important role in the regulation of lipoprotein metabolism and triglyceride (TG) storage. ASP also appears to have a role in the regulation of energy balance. In addition to its role as a hormonal regulator of body weight and energy expenditure, leptin is now implicated as a regulatory molecule in lipid metabolism. However, little is known about the alterations in fasting plasma ASP and leptin concentrations in the nephrotic syndrome. As hyperlipidemia is one of the most striking manifestations of the nephrotic syndrome, we have investigated fasting plasma ASP and leptin levels and their relation to lipid levels in this syndrome. Twenty-five patients with untreated nephrotic syndrome and 25 age-, sex-, and body mass index-matched healthy controls were included in the study. Fasting plasma lipoproteins, TG, total cholesterol, lipoprotein(a), apolipoprotein AI (apoAI), apoB, urinary protein, plasma albumin, third component of complement (C3), ASP, and leptin levels were measured in both groups. Total cholesterol, TG, low and very low density lipoproteins, lipoprotein(a), apoB, and urinary protein levels were increased in the patient group, whereas plasma albumin, high density lipoprotein cholesterol, and apoAI levels were decreased compared with those in the control group (P Fasting ASP concentrations showed no correlation with body mass index, proteinuria, plasma albumin, leptin, or any lipid parameter in either group, but C3 levels (in patient group: r(s) = 0.92; P < 0.001; in control group: r(s) = 0.68; P < 0.001). Our findings showed that plasma ASP levels were significantly elevated, whereas leptin levels were normal in the nephrotic syndrome. Increased ASP levels in the setting of dyslipidemia in the nephrotic syndrome raise the possibility of an ASP receptor defect in adipocytes, which also suggests the existence of so-called ASP resistance. Moreover

  1. Recombinant scFv Antibodies against E Protein and N Protein of Severe Acute Respiratory Syndrome Virus

    Institute of Scientific and Technical Information of China (English)

    Hui LIU; Yan-Li DING; Wei HAN; Mei-Yun LIU; Rui-Yang TIAN; Sheng-Li YANG; Yi GONG

    2004-01-01

    Three single chain antibodies(scFv)against the proteins of severe acute respiratory syndrome coronavirus(SARS-CoV)were isolated by phage display from an scFv antibody library.Bio-panning was carried out against immobilized purified envelope(E)and nucleocapsid(N)proteins of SARS-CoV.Their binding activity and specificity to E or N protein of SARS-CoV were characterized by phage-ELISA.Two of them,B 10 and C20,could recognize non-overlapping epitopes of the E protein according to the two-site binding test result.Clone A 17 could recognize N protein.The sequence of the epitope or overlapping epitope of scFv antibody A17 was PTDSTDNNQNGGRNGARPKQRRPQ.The affinity(equilibrium dissociation constant,Kd)of SARS-CoV E protein was 5.7×10-8 M for B10 and 8.9×10-8 M for C20.The affinity of A17for N protein was 2.1 x 10-6 M.All three scFv antibodies were purified with affinity chromatography and determined by Western blot.

  2. Proteomic analysis of hepatic tissue of Cyprinus carpio L. exposed to cyanobacterial blooms in Lake Taihu, China.

    Directory of Open Access Journals (Sweden)

    Jinlin Jiang

    Full Text Available With the rapid development of industry and agriculture and associated pollution, the cyanobacterial blooms in Lake Taihu have become a major threat to aquatic wildlife and human health. In this study, the ecotoxicological effects of cyanobacterial blooms on cage-cultured carp (Cyprinus carpio L. in Meiliang Bay of Lake Taihu were investigated. Microcystins (MCs, major cyanobacterial toxins, have been detected in carp cultured at different experimental sites of Meiliang Bay. We observed that the accumulation of MCs in carp was closely associated with several environmental factors, including temperature, pH value, and density of cyanobacterial blooms. The proteomic profile of carp liver exposed to cyanobacterial blooms was analyzed using two-dimensional difference in-gel electrophoresis (2D-DIGE and mass spectrometry. The toxic effects of cyanobacterial blooms on carp liver were similar to changes caused by MCs. MCs were transported into liver cells and induced the excessive production of reactive oxygen species (ROS. MCs and ROS inhibited protein phosphatase and aldehyde dehydrogenase (ALDH, directly or indirectly resulting in oxidative stress and disruption of the cytoskeleton. These effects further interfered with metabolic pathways in the liver through the regulation of series of related proteins. The results of this study indicated that cyanobacterial blooms pose a major threat to aquatic wildlife in Meiliang Bay in Lake Taihu. These results provided evidence of the molecular mechanisms underlying liver damage in carp exposed to cyanobacterial blooms.

  3. Marfan Syndrome

    Science.gov (United States)

    Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, ... fibrillin. A problem with the fibrillin gene causes Marfan syndrome. Marfan syndrome can be mild to severe, ...

  4. Listening to the sound of flower blooming

    Institute of Scientific and Technical Information of China (English)

    YAN; Wei-fang

    2015-01-01

    The most beautiful thing in our life is the first glance,and the most beautiful point of fireworks is its evanescent bloom.Thing’s beautiful is usually due to its evanescent exist.It might exist shortly but in our mind for a long time.As for me,the most beautiful thing is to listen to the sound of flower blooming.

  5. Algal blooms and Membrane Based Desalination Technology

    OpenAIRE

    Villacorte, L.O.

    2014-01-01

    Seawater desalination is rapidly growing in terms of installed capacity (~80 million m3/day in 2013), plant size and global application. An emerging threat to this technology is the seasonal proliferation of microscopic algae in seawater known as algal blooms. Such blooms have caused operational problems in seawater reverse osmosis (SWRO) plants due to clogging and poor effluent quality of the pre-treatment system which eventually forced the shutdown of the plant to avoid irreversible fouling...

  6. Algal blooms and Membrane Based Desalination Technology

    OpenAIRE

    Villacorte, L.O.

    2014-01-01

    Seawater desalination is rapidly growing in terms of installed capacity (~80 million m3/day in 2013), plant size and global application. An emerging threat to this technology is the seasonal proliferation of microscopic algae in seawater known as algal blooms. Such blooms have caused operational problems in seawater reverse osmosis (SWRO) plants due to clogging and poor effluent quality of the pre-treatment system which eventually forced the shutdown of the plant to avoid irreversible fouling...

  7. Bloom's taxonomy of cognitive learning objectives.

    Science.gov (United States)

    Adams, Nancy E

    2015-07-01

    Information professionals who train or instruct others can use Bloom's taxonomy to write learning objectives that describe the skills and abilities that they desire their learners to master and demonstrate. Bloom's taxonomy differentiates between cognitive skill levels and calls attention to learning objectives that require higher levels of cognitive skills and, therefore, lead to deeper learning and transfer of knowledge and skills to a greater variety of tasks and contexts.

  8. Bloom's Taxonomy and Training in Programming Style

    OpenAIRE

    Teodosi TEODOSIEV

    2013-01-01

    Report published in the Proceedings of the National Conference on "Education in the Information Society", Plovdiv, May, 2013 The presented work is using Bloom's taxonomy to set the goals of teaching programming. Here are shown the elements of programming style, in which you can teach novices. Elements of programming style are at different levels of Bloom's pyramid. Association for the Development of the Information Society, Institute of Mathematics and Informatics Bulgarian Academ...

  9. Tumor suppressor p53 protein expression: prognostic significance in patients with low-risk myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Fernando Barroso Duarte

    2014-06-01

    Full Text Available BACKGROUND: At the time of diagnosis, more than 50% of patients with myelodysplastic syndrome have a normal karyotype and are classified as having a favorable prognosis. However, these patients often show very variable clinical outcomes. Furthermore, current diagnostic tools lack the ability to look at genetic factors beyond karyotyping in order to determine the cause of this variability.OBJECTIVE: To evaluate the impact of p53 protein expression at diagnosis in patients with low-risk myelodysplastic syndrome.METHODS: This study enrolled 38 patients diagnosed with low-risk myelodysplastic syndrome. Clinical data were collected by reviewing medical records, and immunohistochemical p53 staining was performed on bone marrow biopsies.RESULTS: Of the 38 participants, 13 (34.21% showed p53 expression in their bone marrow. At diagnosis, this group of patients also presented clinical features characteristic of a poor prognosis more often than patients who did not express p53. Furthermore, patients expressing p53 had a shorter median survival time compared to those without p53 expression.CONCLUSION: This study shows that the expression of p53 at diagnosis is a useful indicator of distinct clinical characteristics and laboratory profiles found in low-risk myelodysplastic syndrome patients. These data indicate that the immunohistochemical analysis of p53 may be a prognostic tool for myelodysplastic syndrome and should be used as an auxiliary test to help determine the best therapeutic choice.

  10. Uncoupling proteins, dietary fat and the metabolic syndrome

    OpenAIRE

    2006-01-01

    Abstract There has been intense interest in defining the functions of UCP2 and UCP3 during the nine years since the cloning of these UCP1 homologues. Current data suggest that both UCP2 and UCP3 proteins share some features with UCP1, such as the ability to reduce mitochondrial membrane potential, but they also have distinctly different physiological roles. Human genetic studies consistently demonstrate the effect of UCP2 alleles on type-2 diabetes. Less clear is whether UCP2 alleles influenc...

  11. Multiple proteins of White spot syndrome virus involved in recognition of -integrin

    Indian Academy of Sciences (India)

    Jing-Yan Zhang; Qing-Hui Liu; Jie Huang

    2014-06-01

    The recognition and attachment of virus to its host cell surface is a critical step for viral infection. Recent research revealed that -integrin was involved in White spot syndrome virus (WSSV) infection. In this study, the interaction of -integrin with structure proteins of WSSV and motifs involved in WSSV infection was examined. The results showed that envelope proteins VP26, VP31, VP37, VP90 and nucleocapsid protein VP136 interacted with LvInt. RGD-, YGL- and LDV-related peptide functioned as motifs of WSSV proteins binding with -integrin. The -integrin ligand of RGDT had better blocking effect compared with that of YGL- and LDV-related peptides. In vivo assay indicated that RGD-, LDV- and YGL-related peptides could partially block WSSV infection. These data collectively indicate that multiple proteins were involved in recognition of -integrin. Identification of proteins in WSSV that are associated with -integrin will assist development of new agents for effective control of the white spot syndrome.

  12. Rainfall-enhanced blooming in typhoon wakes

    Science.gov (United States)

    Lin, Y.-C.; Oey, L.-Y.

    2016-08-01

    Strong phytoplankton blooming in tropical-cyclone (TC) wakes over the oligotrophic oceans potentially contributes to long-term changes in global biogeochemical cycles. Yet blooming has traditionally been discussed using anecdotal events and its biophysical mechanics remain poorly understood. Here we identify dominant blooming patterns using 16 years of ocean-color data in the wakes of 141 typhoons in western North Pacific. We observe right-side asymmetric blooming shortly after the storms, attributed previously to sub-mesoscale re-stratification, but thereafter a left-side asymmetry which coincides with the left-side preference in rainfall due to the large-scale wind shear. Biophysical model experiments and observations demonstrate that heavier rainfall freshens the near-surface water, leading to stronger stratification, decreased turbulence and enhanced blooming. Our results suggest that rainfall plays a previously unrecognized, critical role in TC-induced blooming, with potentially important implications for global biogeochemical cycles especially in view of the recent and projected increases in TC-intensity that harbingers stronger mixing and heavier rain under the storm.

  13. Relationship of C-reactive protein with components of the metabolic syndrome in normal-weight and overweight elderly

    NARCIS (Netherlands)

    Hoekstra, T.; Geleijnse, J.M.; Schouten, E.G.; Kluft, C.; Kok, F.J.

    2005-01-01

    C-reactive protein (CRP) is known to be elevated in the metabolic syndrome. We aimed to explore in more detail the relationship between CRP and other components of the metabolic syndrome in a general population of 605 Dutch elderly individuals aged 65¿84 years. Methods and results Data were collecte

  14. TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome

    NARCIS (Netherlands)

    Lambacher, Nils J; Bruel, Ange-Line; van Dam, Teunis J P; Szymańska, Katarzyna; Slaats, Gisela G; Kuhns, Stefanie; McManus, Gavin J; Kennedy, Julie E; Gaff, Karl; Wu, Ka Man; van der Lee, Robin; Burglen, Lydie; Doummar, Diane; Rivière, Jean-Baptiste; Faivre, Laurence; Attié-Bitach, Tania; Saunier, Sophie; Curd, Alistair; Peckham, Michelle; Giles, R|info:eu-repo/dai/nl/173658725; Johnson, Colin A; Huynen, Martijn A; Thauvin-Robinet, Christel; Blacque, Oliver E

    2016-01-01

    The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS). However, t

  15. TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome

    NARCIS (Netherlands)

    Lambacher, Nils J; Bruel, Ange-Line; van Dam, Teunis J P; Szymańska, Katarzyna; Slaats, Gisela G; Kuhns, Stefanie; McManus, Gavin J; Kennedy, Julie E; Gaff, Karl; Wu, Ka Man; van der Lee, Robin; Burglen, Lydie; Doummar, Diane; Rivière, Jean-Baptiste; Faivre, Laurence; Attié-Bitach, Tania; Saunier, Sophie; Curd, Alistair; Peckham, Michelle; Giles, R; Johnson, Colin A; Huynen, Martijn A; Thauvin-Robinet, Christel; Blacque, Oliver E

    The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS). However,

  16. Identification of the Nucleocapsid, Tegument, and Envelope Proteins of the Shrimp White Spot Syndrome Virus Virion

    Science.gov (United States)

    Tsai, Jyh-Ming; Wang, Han-Ching; Leu, Jiann-Horng; Wang, Andrew H.-J.; Zhuang, Ying; Walker, Peter J.; Kou, Guang-Hsiung; Lo, Chu-Fang

    2006-01-01

    The protein components of the white spot syndrome virus (WSSV) virion have been well established by proteomic methods, and at least 39 structural proteins are currently known. However, several details of the virus structure and assembly remain controversial, including the role of one of the major structural proteins, VP26. In this study, Triton X-100 was used in combination with various concentrations of NaCl to separate intact WSSV virions into distinct fractions such that each fraction contained envelope and tegument proteins, tegument and nucleocapsid proteins, or nucleocapsid proteins only. From the protein profiles and Western blotting results, VP26, VP36A, VP39A, and VP95 were all identified as tegument proteins distinct from the envelope proteins (VP19, VP28, VP31, VP36B, VP38A, VP51B, VP53A) and nucleocapsid proteins (VP664, VP51C, VP60B, VP15). We also found that VP15 dissociated from the nucleocapsid at high salt concentrations, even though DNA was still present. These results were confirmed by CsCl isopycnic centrifugation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry, by a trypsin sensitivity assay, and by an immunogold assay. Finally, we propose an assembly process for the WSSV virion. PMID:16501111

  17. Cockayne Syndrome group B protein stimulates NEIL2 DNA glycosylase activity

    DEFF Research Database (Denmark)

    Aamann, Maria Diget; Hvitby, Christina Poulsen; Popuri, Venkateswarlu

    2014-01-01

    Cockayne Syndrome is a segmental premature aging syndrome, which can be caused by loss of function of the CSB protein. CSB is essential for genome maintenance and has numerous interaction partners with established roles in different DNA repair pathways including transcription coupled nucleotide...... excision repair and base excision repair. Here, we describe a new interaction partner for CSB, the DNA glycosylase NEIL2. Using both cell extracts and recombinant proteins, CSB and NEIL2 were found to physically interact independently of DNA. We further found that CSB is able to stimulate NEIL2 glycosylase...... in a DNA bubble structure using whole cell extracts. Taken together, our data supports a biological role for CSB and NEIL2 in transcription associated base excision repair....

  18. Transient overexpression of Werner protein rescues starvation induced autophagy in Werner syndrome cells.

    Science.gov (United States)

    Maity, Jyotirindra; Bohr, Vilhelm A; Laskar, Aparna; Karmakar, Parimal

    2014-12-01

    Reduced autophagy may be associated with normal and pathological aging. Here we report a link between autophagy and Werner protein (WRNp), mutated in Werner syndrome, the human premature aging Werner syndrome (WS). WRN mutant fibroblast AG11395 and AG05229 respond weakly to starvation induced autophagy compared to normal cells. While the fusion of phagosomes with lysosome is normal, WS cells contain fewer autophagy vacuoles. Cellular starvation autophagy in WS cells is restored after transfection with full length WRN. Further, siRNA mediated silencing of WRN in the normal fibroblast cell line WI-38 results in decreased autophagy and altered expression of autophagy related proteins. Thus, our observations suggest that WRN may have a role in controlling autophagy and hereby cellular maintenance.

  19. Production of polyclonal antiserum specific to the 27.5 kDa envelope protein of white spot syndrome virus

    NARCIS (Netherlands)

    You, Z.O.; Nadala, E.C.B.; Yang, J.S.; Hulten, van M.C.W.; Loh, P.C.

    2002-01-01

    A truncated version of the white spot syndrome virus (WSSV) 27.5 kDa envelope protein was expressed as a histidine tag fusion protein in Escherichia coli. The bacterial expression system allowed the production of up to 10 mg of purified recombinant protein per liter of bacterial culture. Antiserum f

  20. Production of polyclonal antiserum specific to the 27.5 kDa envelope protein of white spot syndrome virus

    NARCIS (Netherlands)

    You, Z.O.; Nadala, E.C.B.; Yang, J.S.; Hulten, van M.C.W.; Loh, P.C.

    2002-01-01

    A truncated version of the white spot syndrome virus (WSSV) 27.5 kDa envelope protein was expressed as a histidine tag fusion protein in Escherichia coli. The bacterial expression system allowed the production of up to 10 mg of purified recombinant protein per liter of bacterial culture. Antiserum f

  1. Relationship between high-sensitivity C-reactive protein and obesity / metabolic syndrome in children

    Institute of Scientific and Technical Information of China (English)

    陈芳芳

    2014-01-01

    Objective To explore the relationship between highsensitivity C-reactive protein(hsC RP)and obesity/metabolic syndrome(MetS)related factors in children.Methods 403 children aged 10-14 and born in Beijing were involved in this study.Height,weight,waist circumference,fat mass percentage(Fat%),blood pressure(BP),hsC RP,triglyceride(TG),total cholesterol

  2. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis.

    Directory of Open Access Journals (Sweden)

    Jose L Nieto-Torres

    2014-05-01

    Full Text Available Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV envelope (E gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+/K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS

  3. Characterization and interactome study of white spot syndrome virus envelope protein VP11.

    Directory of Open Access Journals (Sweden)

    Wang-Jing Liu

    Full Text Available White spot syndrome virus (WSSV is a large enveloped virus. The WSSV viral particle consists of three structural layers that surround its core DNA: an outer envelope, a tegument and a nucleocapsid. Here we characterize the WSSV structural protein VP11 (WSSV394, GenBank accession number AF440570, and use an interactome approach to analyze the possible associations between this protein and an array of other WSSV and host proteins. Temporal transcription analysis showed that vp11 is an early gene. Western blot hybridization of the intact viral particles and fractionation of the viral components, and immunoelectron microscopy showed that VP11 is an envelope protein. Membrane topology software predicted VP11 to be a type of transmembrane protein with a highly hydrophobic transmembrane domain at its N-terminal. Based on an immunofluorescence assay performed on VP11-transfected Sf9 cells and a trypsin digestion analysis of the virion, we conclude that, contrary to topology software prediction, the C-terminal of this protein is in fact inside the virion. Yeast two-hybrid screening combined with co-immunoprecipitation assays found that VP11 directly interacted with at least 12 other WSSV structural proteins as well as itself. An oligomerization assay further showed that VP11 could form dimers. VP11 is also the first reported WSSV structural protein to interact with the major nucleocapsid protein VP664.

  4. Characterization and interactome study of white spot syndrome virus envelope protein VP11.

    Science.gov (United States)

    Liu, Wang-Jing; Shiung, Hui-Jui; Lo, Chu-Fang; Leu, Jiann-Horng; Lai, Ying-Jang; Lee, Tai-Lin; Huang, Wei-Tung; Kou, Guang-Hsiung; Chang, Yun-Shiang

    2014-01-01

    White spot syndrome virus (WSSV) is a large enveloped virus. The WSSV viral particle consists of three structural layers that surround its core DNA: an outer envelope, a tegument and a nucleocapsid. Here we characterize the WSSV structural protein VP11 (WSSV394, GenBank accession number AF440570), and use an interactome approach to analyze the possible associations between this protein and an array of other WSSV and host proteins. Temporal transcription analysis showed that vp11 is an early gene. Western blot hybridization of the intact viral particles and fractionation of the viral components, and immunoelectron microscopy showed that VP11 is an envelope protein. Membrane topology software predicted VP11 to be a type of transmembrane protein with a highly hydrophobic transmembrane domain at its N-terminal. Based on an immunofluorescence assay performed on VP11-transfected Sf9 cells and a trypsin digestion analysis of the virion, we conclude that, contrary to topology software prediction, the C-terminal of this protein is in fact inside the virion. Yeast two-hybrid screening combined with co-immunoprecipitation assays found that VP11 directly interacted with at least 12 other WSSV structural proteins as well as itself. An oligomerization assay further showed that VP11 could form dimers. VP11 is also the first reported WSSV structural protein to interact with the major nucleocapsid protein VP664.

  5. Biology in Bloom: Implementing Bloom's Taxonomy to Enhance Student Learning in Biology

    Science.gov (United States)

    Crowe, Alison; Dirks, Clarissa; Wenderoth, Mary Pat

    2008-01-01

    We developed the Blooming Biology Tool (BBT), an assessment tool based on Bloom's Taxonomy, to assist science faculty in better aligning their assessments with their teaching activities and to help students enhance their study skills and metacognition. The work presented here shows how assessment tools, such as the BBT, can be used to guide and…

  6. Association among Fibrinolytic Proteins, Metabolic Syndrome Components, Insulin Secretion, and Resistance in Schoolchildren

    Directory of Open Access Journals (Sweden)

    Jin-Shuen Chen

    2015-01-01

    Full Text Available We investigated the role of urokinase plasminogen activator (uPA and its soluble receptors (suPAR and plasminogen activator inhibitor-1 (PAI-1 in metabolic syndrome (MetS components, insulin secretion, and resistance in schoolchildren. We enrolled 387 children, aged 10.3 ± 1.5 years, in Taipei. Anthropometry, fibrinolytic proteins, MetS components, insulin secretion, and resistance were measured. Subjects were divided into normal, overweight, and obese groups. Finally, the relationship between fibrinolytic proteins and metabolic syndrome in boys and girls was analyzed. In boys, PAI-1 was positively associated with body mass index (BMI percentile, hypertriglyceride, insulin secretion, and resistance. In girls, PAI-1 was positively associated with obesity, hypertriglyceridemia, and insulin secretion. In girls, uPA was positively associated with insulin secretion. suPAR was positively associated with high-sensitivity C-reactive protein in both boys and girls, and with BMI percentile and body fat in girls. The obese boys had higher suPAR and PAI-1 levels than the normal group. The obese girls had higher uPA, suPAR, and PAI-1 than the normal group. Boys and girls with MetS had higher PAI-1. Fibrinolytic proteins, especially PAI-1, are associated with MetS components and insulin secretion in children. Fibrinolytic proteins changes were more likely to occur in girls than in boys.

  7. DNA condensates organized by the capsid protein VP15 in White Spot Syndrome Virus.

    Science.gov (United States)

    Liu, Yingjie; Wu, Jinlu; Chen, Hu; Hew, Choy Leong; Yan, Jie

    2010-12-20

    The White Spot Syndrome Virus (WSSV) has a large circular double-stranded DNA genome of around 300kb and it replicates in the nucleus of the host cells. The machinery of how the viral DNA is packaged has been remained unclear. VP15, a highly basic protein, is one of the major capsid proteins found in the virus. Previously, it was shown to be a DNA binding protein and was hypothesized to participate in the viral DNA packaging process. Using Atomic Force Microscopy imaging, we show that the viral DNA is associated with a (or more) capsid proteins. The organized viral DNA qualitatively resembles the conformations of VP15 induced DNA condensates in vitro. Furthermore, single-DNA manipulation experiments revealed that VP15 is able to condense single DNA against forces of a few pico Newtons. Our results suggest that VP15 may aid in the viral DNA packaging process by directly condensing DNA.

  8. Cyanobacteria blooms produce teratogenic retinoic acids.

    Science.gov (United States)

    Wu, Xiaoqin; Jiang, Jieqiong; Wan, Yi; Giesy, John P; Hu, Jianying

    2012-06-12

    Deformed amphibians have been observed in eutrophic habitats, and some clues point to the retinoic acids (RAs) or RA mimics. However, RAs are generally thought of as vertebrate-specific hormones, and there was no evidence that RAs exist in cyanobacteria or algae blooms. By analyzing RAs and their analogs 4-oxo-RAs in natural cyanobacteria blooms and cultures of cyanobacteria and algae, we showed that cyanobacteria blooms could produce RAs, which were powerful animal teratogens. Intracellular RAs and 4-oxo-RAs with concentrations between 0.4 and 4.2 × 10(2) ng/L were detected in all bloom materials, and extracellular concentrations measured in water from Taihu Lake, China, were as great as 2.0 × 10 ng/L, which might pose a risk to wildlife through chronic exposure. Further examination of 39 cyanobacteria and algae species revealed that 32 species could produce RAs and 4-oxo-RAs (1.6-1.4 × 10(3) ng/g dry weight), and the dominant cyanobacteria species in Taihu Lake, Microcystis flos-aquae and Microcystis aeruginosa, produced high amounts of RAs and 4-oxo-RAs with concentrations of 1.4 × 10(3) and 3.7 × 10(2) ng/g dry weight, respectively. Most genera of cyanobacteria that could produce RAs and 4-oxo-RAs, such as Microcystis, Anabaena, and Aphanizomenon, often occur dominantly in blooms. Production of RAs and 4-oxo-RAs by cyanobacteria was associated with species, origin location, and growth stage. These results represent a conclusive demonstration of endogenous production of RAs in freshwater cyanobacteria blooms. The observation of teratogenic RAs in cyanobacteria is evolutionarily and ecologically significant because RAs are vertebrate-specific hormones, and cyanobacteria form extensive and highly visible blooms in many aquatic ecosystems.

  9. A 3D model of the membrane protein complex formed by the white spot syndrome virus structural proteins.

    Directory of Open Access Journals (Sweden)

    Yun-Shiang Chang

    Full Text Available BACKGROUND: Outbreaks of white spot disease have had a large negative economic impact on cultured shrimp worldwide. However, the pathogenesis of the causative virus, WSSV (whit spot syndrome virus, is not yet well understood. WSSV is a large enveloped virus. The WSSV virion has three structural layers surrounding its core DNA: an outer envelope, a tegument and a nucleocapsid. In this study, we investigated the protein-protein interactions of the major WSSV structural proteins, including several envelope and tegument proteins that are known to be involved in the infection process. PRINCIPAL FINDINGS: In the present report, we used coimmunoprecipitation and yeast two-hybrid assays to elucidate and/or confirm all the interactions that occur among the WSSV structural (envelope and tegument proteins VP51A, VP19, VP24, VP26 and VP28. We found that VP51A interacted directly not only with VP26 but also with VP19 and VP24. VP51A, VP19 and VP24 were also shown to have an affinity for self-interaction. Chemical cross-linking assays showed that these three self-interacting proteins could occur as dimers. CONCLUSIONS: From our present results in conjunction with other previously established interactions we construct a 3D model in which VP24 acts as a core protein that directly associates with VP26, VP28, VP38A, VP51A and WSV010 to form a membrane-associated protein complex. VP19 and VP37 are attached to this complex via association with VP51A and VP28, respectively. Through the VP26-VP51C interaction this envelope complex is anchored to the nucleocapsid, which is made of layers of rings formed by VP664. A 3D model of the nucleocapsid and the surrounding outer membrane is presented.

  10. Biomass decay rates and tissue nutrient loss in bloom and non-bloom-forming macroalgal species

    Science.gov (United States)

    Conover, Jessie; Green, Lindsay A.; Thornber, Carol S.

    2016-09-01

    Macroalgal blooms occur in shallow, low-wave energy environments and are generally dominated by fast-growing ephemeral macroalgae. When macroalgal mats undergo senescence and decompose they can cause oxygen depletion and release nutrients into the surrounding water. There are relatively few studies that examine macroalgal decomposition rates in areas impacted by macroalgal blooms. Understanding the rate of macroalgal bloom decomposition is essential to understanding the impacts of macroalgal blooms following senescence. Here, we examined the biomass, organic content, nitrogen decay rates and δ15N values for five macroalgal species (the bloom-forming Agardhiella subulata, Gracilaria vermiculophylla, Ulva compressa, and Ulva rigida and the non-bloom-forming Fucus vesiculosus) in Narragansett Bay, Rhode Island, U.S.A. using a litterbag design. Bloom-forming macroalgae had similar biomass decay rates (0.34-0.51 k d-1) and decayed significantly faster than non-bloom-forming macroalgae (0.09 k d-1). Biomass decay rates also varied temporally, with a significant positive correlation between biomass decay rate and water temperature for U. rigida. Tissue organic content decreased over time in all species, although A. subulata and G. vermiculophylla displayed significantly higher rates of organic content decay than U. compressa, U. rigida, and F. vesiculosus. Agardhiella subulata had a significantly higher rate of tissue nitrogen decay (0.35 k d-1) than all other species. By contrast, only the δ15N of F. vesiculosus changed significantly over the decay period. Overall, our results indicate that bloom-forming macroalgal species decay more rapidly than non-bloom-forming species.

  11. Identification of defects in the fibrillin gene and protein in individuals with the Marfan syndrome and related disorders.

    Science.gov (United States)

    Milewicz, D M

    1994-01-01

    The Marfan syndrome is an autosomal dominant disorder with pleiotropic manifestations that involve the cardiovascular, ocular, and skeletal systems. Through a number of investigational approaches, the gene encoding for fibrillin, the FBN1 gene on chromosome 15, has been identified as the defective gene causing the Marfan syndrome. Fibrillin is the large glycoprotein with a repetitive domain structure and is a major protein component of microfibrils, a fibrillar system closely associated with elastin in connective tissue. Mutational analysis of defects in the FBN1 gene in patients with the Marfan syndrome has revealed that most mutations are private or unique in an affected individual or family. Analysis of fibrillin protein or gene defects in individuals with related phenotypes has revealed that a perinatal lethal syndrome, termed neonatal Marfan syndrome, is due to FBN1 gene mutations. In addition, fibroblast cell strains from a subset of patients with idiopathic scoliosis have fibrillin protein defects. Last, fibroblasts from calves affected with bovine Marfan syndrome display defects in the fibrillin protein. These studies have wide-ranging implications in the diagnosis, treatment, and prevention of Marfan syndrome and related disorders. Images PMID:8180508

  12. A subunit vaccine against the adenovirus egg-drop syndrome using part of its fiber protein.

    Science.gov (United States)

    Fingerut, E; Gutter, B; Gallili, G; Michael, A; Pitcovski, J

    2003-06-20

    In this study, the effectiveness of antibodies against the hexon, fiber or a fiber fragment of an avian adenovirus egg-drop syndrome (EDS), in neutralizing the virus was tested. The fiber protein is responsible for binding the virus to the target cell. The fiber fragment knob-s comprises the carboxy-terminal knob domain and 34 amino acids of the immediately adjacent shaft domain of the adenovirus fiber protein. The hexon, fiber capsid protein and knob-s were produced in E. coli and injected into chickens. Antibodies that were produced against the whole fiber protein showed some hemagglutination inhibition (HI) activity. Antibodies produced against the knob-s protein showed HI activity and serum neutralization (SN) activity similar to the positive control-whole virus vaccine. We assume that production of only part of the fiber enables the protein produced in E. coli to fold correctly. Antibodies produced against the hexon protein showed no SN activity. In summary, knob-s induced SN and HI antibodies against EDS virus at a rate similar to the whole virus and were significantly more efficient than the full-length fiber. The recombinant knob-s protein may be used as a vaccine against pathogenic adenovirus infections.

  13. Protein-Based Classifier to Predict Conversion from Clinically Isolated Syndrome to Multiple Sclerosis.

    Science.gov (United States)

    Borràs, Eva; Cantó, Ester; Choi, Meena; Maria Villar, Luisa; Álvarez-Cermeño, José Carlos; Chiva, Cristina; Montalban, Xavier; Vitek, Olga; Comabella, Manuel; Sabidó, Eduard

    2016-01-01

    Multiple sclerosis is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. In most patients, the disease initiates with an episode of neurological disturbance referred to as clinically isolated syndrome, but not all patients with this syndrome develop multiple sclerosis over time, and currently, there is no clinical test that can conclusively establish whether a patient with a clinically isolated syndrome will eventually develop clinically defined multiple sclerosis. Here, we took advantage of the capabilities of targeted mass spectrometry to establish a diagnostic molecular classifier with high sensitivity and specificity able to differentiate between clinically isolated syndrome patients with a high and a low risk of developing multiple sclerosis. Based on the combination of abundances of proteins chitinase 3-like 1 and ala-β-his-dipeptidase in cerebrospinal fluid, we built a statistical model able to assign to each patient a precise probability of conversion to clinically defined multiple sclerosis. Our results are of special relevance for patients affected by multiple sclerosis as early treatment can prevent brain damage and slow down the disease progression.

  14. Phytoplankton Bloom Phenology near Palmer Station Antarctica

    Science.gov (United States)

    Crews, L.; Doney, S. C.; Kavanaugh, M.; Ducklow, H. W.; Schofield, O.; Glover, D. M.

    2015-12-01

    West Antarctic Peninsula (WAP) phytoplankton bloom phenology is coupled to growing season water column stratification precipitated by seasonal warming and the melting of winter sea-ice. Previous studies document declining bloom magnitude over decadal timescales in conjunction with decreasing sea-ice extent and duration in the Northern WAP, but less work has been to done explain the observed inter-annual variability in this region. Here we use a high-resolution in situ time series collected by the Palmer Station Antarctica Long Term Ecological Research program and satellite ocean color imagery to investigate the underlying mechanisms controlling phytoplankton bloom timing and magnitude near Palmer Station. We pair chlorophyll and CTD measurements collected twice per week during the austral summer, 1992—2003, with satellite ocean color and ice fractional cover data to examine bloom development and within-season trends in mixed layer depth. Initial results suggest a possible shift over time with spring/summer blooms occurring earlier in the growing season reflecting earlier sea-ice free conditions. Net phytoplankton accumulation rates are also computed and compared against growth estimates. Our results can be used to develop and validate models of coastal Antarctic primary production that better represent inter-annual primary production variability.

  15. Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization.

    Science.gov (United States)

    Twigg, Stephen R F; Lloyd, Deborah; Jenkins, Dagan; Elçioglu, Nursel E; Cooper, Christopher D O; Al-Sannaa, Nouriya; Annagür, Ali; Gillessen-Kaesbach, Gabriele; Hüning, Irina; Knight, Samantha J L; Goodship, Judith A; Keavney, Bernard D; Beales, Philip L; Gileadi, Opher; McGowan, Simon J; Wilkie, Andrew O M

    2012-11-02

    Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed.

  16. Engineered mutations in fibrillin-1 leading to Marfan syndrome act at the protein, cellular and organismal levels.

    Science.gov (United States)

    Zeyer, Karina A; Reinhardt, Dieter P

    2015-01-01

    Fibrillins are the major components of microfibrils in the extracellular matrix of elastic and non-elastic tissues. They are multi-domain proteins, containing primarily calcium binding epidermal growth factor-like (cbEGF) domains and 8-cysteine/transforming growth factor-beta binding protein-like (TB) domains. Mutations in the fibrillin-1 gene give rise to Marfan syndrome, a connective tissue disorder with clinical complications in the cardiovascular, skeletal, ocular and other organ systems. Here, we review the consequences of engineered Marfan syndrome mutations in fibrillin-1 at the protein, cellular and organismal levels. Representative point mutations associated with Marfan syndrome in affected individuals have been introduced and analyzed in recombinant fibrillin-1 fragments. Those mutations affect fibrillin-1 on a structural and functional level. Mutations which impair folding of cbEGF domains can affect protein trafficking. Protein folding disrupted by some mutations can lead to defective secretion in mutant fibrillin-1 fragments, whereas fragments with other Marfan mutations are secreted normally. Many Marfan mutations render fibrillin-1 more susceptible to proteolysis. There is also evidence that some mutations affect heparin binding. Few mutations have been further analyzed in mouse models. An extensively studied mouse model of Marfan syndrome expresses mouse fibrillin-1 with a missense mutation (p.C1039G). The mice display similar characteristics to human patients with Marfan syndrome. Overall, the analyses of engineered mutations leading to Marfan syndrome provide important insights into the pathogenic molecular mechanisms exerted by mutated fibrillin-1.

  17. Proteomic analysis of the alteration of protein expression in the placenta of Down syndrome

    Institute of Scientific and Technical Information of China (English)

    SUN Cheng-juan; YAN Li-yu; WANG Wei; YU Song; WANG Xin; ZHANG Wei-yuan

    2011-01-01

    Background Down syndrome (DS) is the most common form of human aneuploidy,and there is no effective therapy for the chromosomal abnormalities.We aimed to unravel the molecular mechanisms underlying DS and to provide clues to prenatal screening.Methods A series of proteomics-based experiments was conducted using 19 patients with DS fetuses and 17 normal pregnancies.The proteome of placenta was investigated as displayed by two-dimensional difference gel electrophoresis (2D-DIGE),and comparisons were made between placentas that developed under DS and normal pregnancy conditions.Multivariate analysis of the resulting protein patterns revealed DS-specific protein expression.Matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight (TOF/TOF) high-resolution tandem mass spectrometer (MS)-based identification was successful for 12 out of 17 selected protein spots.Results Among those,three proteins involved in the resist of reactive oxygen species (ROS) and neurogenesis were more abundant in the DS placenta (superoxide dismutase 1,endoplasmic reticulum protein 29 and heat shock protein beta-1),while peroxiredoxin-6 involved in cell defense mechanism against ROS was expressed at a higher level in the normal pregnancies.Conclusion Knowledge of the DS placenta proteome emphasizes the role of proteins involved in anti-oxidation during DS,and may form the basis of a potential approach to minimize the incidence of DS in the clinical setting.

  18. The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis

    Science.gov (United States)

    McBride, Ruth; Fielding, Burtram C.

    2012-01-01

    A respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), was first reported in China in late 2002. The subsequent efficient human-to-human transmission of this virus eventually affected more than 30 countries worldwide, resulting in a mortality rate of ~10% of infected individuals. The spread of the virus was ultimately controlled by isolation of infected individuals and there has been no infections reported since April 2004. However, the natural reservoir of the virus was never identified and it is not known if this virus will re-emerge and, therefore, research on this virus continues. The SARS-CoV genome is about 30 kb in length and is predicted to contain 14 functional open reading frames (ORFs). The genome encodes for proteins that are homologous to known coronavirus proteins, such as the replicase proteins (ORFs 1a and 1b) and the four major structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E). SARS-CoV also encodes for eight unique proteins, called accessory proteins, with no known homologues. This review will summarize the current knowledge on SARS-CoV accessory proteins and will include: (i) expression and processing; (ii) the effects on cellular processes; and (iii) functional studies. PMID:23202509

  19. The role of white spot syndrome virus (WSSV) VP466 protein in shrimp antiviral phagocytosis.

    Science.gov (United States)

    Ye, Ting; Zong, Rongrong; Zhang, Xiaobo

    2012-08-01

    Widespread evidence indicates that the structural proteins of virus play very important roles in virus-host interactions. However, the effect of viral proteins on host immunity has not been addressed. Our previous studies revealed that the host shrimp Rab6 (termed as PjRab previously), tropomyosin, β-actin and the white spot syndrome virus (WSSV) envelope protein VP466 formed a complex. In this study, the VP466 protein was shown to be able to bind host Rab6 protein and increase its GTPase activity in vivo and vitro. Thus, VP466 could function as a GTPase-activating protein (GAP) of Rab6. In the VP466-Rab-actin pathway, the increase of the Rab6 activity induced rearrangements of the actin cytoskeleton, resulting in the formation of actin stress fibers which promoted the phagocytosis against virus. Therefore our findings revealed that a viral protein could be employed by host to initiate the host immunity, representing a novel molecular mechanism in the virus-host interaction. Our study would help to better understand the molecular events in immune response against virus infection in invertebrates.

  20. Metabolic syndrome: adenosine monophosphate-activated protein kinase and malonyl coenzyme A.

    Science.gov (United States)

    Ruderman, Neil B; Saha, Asish K

    2006-02-01

    The metabolic syndrome can be defined as a state of metabolic dysregulation characterized by insulin resistance, central obesity, and a predisposition to type 2 diabetes, dyslipidemia, premature atherosclerosis, and other diseases. An increasing body of evidence has linked the metabolic syndrome to abnormalities in lipid metabolism that ultimately lead to cellular dysfunction. We review here the hypothesis that, in many instances, the cause of these lipid abnormalities could be a dysregulation of the adenosine monophosphate-activated protein kinase (AMPK)/malonyl coenzyme A (CoA) fuel-sensing and signaling mechanism. Such dysregulation could be reflected by isolated increases in malonyl CoA or by concurrent changes in malonyl CoA and AMPK, both of which would alter intracellular fatty acid partitioning. The possibility is also raised that pharmacological agents and other factors that activate AMPK and/or decrease malonyl CoA could be therapeutic targets.

  1. Envelope Proteins of White Spot Syndrome Virus (WSSV Interact with Litopenaeus vannamei Peritrophin-Like Protein (LvPT.

    Directory of Open Access Journals (Sweden)

    Shijun Xie

    Full Text Available White spot syndrome virus (WSSV is a major pathogen in shrimp cultures. The interactions between viral proteins and their receptors on the surface of cells in a frontier target tissue are crucial for triggering an infection. In this study, a yeast two-hybrid (Y2H library was constructed using cDNA obtained from the stomach and gut of Litopenaeus vannamei, to ascertain the role of envelope proteins in WSSV infection. For this purpose, VP37 was used as the bait in the Y2H library screening. Forty positive clones were detected after screening. The positive clones were analyzed and discriminated, and two clones belonging to the peritrophin family were subsequently confirmed as genuine positive clones. Sequence analysis revealed that both clones could be considered as the same gene, LV-peritrophin (LvPT. Co-immunoprecipitation confirmed the interaction between LvPT and VP37. Further studies in the Y2H system revealed that LvPT could also interact with other WSSV envelope proteins such as VP32, VP38A, VP39B, and VP41A. The distribution of LvPT in tissues revealed that LvPT was mainly expressed in the stomach than in other tissues. In addition, LvPT was found to be a secretory protein, and its chitin-binding ability was also confirmed.

  2. Regulation of ciliary retrograde protein trafficking by the Joubert syndrome proteins ARL13B and INPP5E.

    Science.gov (United States)

    Nozaki, Shohei; Katoh, Yohei; Terada, Masaya; Michisaka, Saki; Funabashi, Teruki; Takahashi, Senye; Kontani, Kenji; Nakayama, Kazuhisa

    2017-02-01

    ARL13B (a small GTPase) and INPP5E (a phosphoinositide 5-phosphatase) are ciliary proteins encoded by causative genes of Joubert syndrome. We here showed, by taking advantage of a visible immunoprecipitation assay, that ARL13B interacts with the IFT46 -: IFT56 (IFT56 is also known as TTC26) dimer of the intraflagellar transport (IFT)-B complex, which mediates anterograde ciliary protein trafficking. However, the ciliary localization of ARL13B was found to be independent of its interaction with IFT-B, but dependent on the ciliary-targeting sequence RVEP in its C-terminal region. ARL13B-knockout cells had shorter cilia than control cells and exhibited aberrant localization of ciliary proteins, including INPP5E. In particular, in ARL13B-knockout cells, the IFT-A and IFT-B complexes accumulated at ciliary tips, and GPR161 (a negative regulator of Hedgehog signaling) could not exit cilia in response to stimulation with Smoothened agonist. This abnormal phenotype was rescued by the exogenous expression of wild-type ARL13B, as well as by its mutant defective in the interaction with IFT-B, but not by its mutants defective in INPP5E binding or in ciliary localization. Thus, ARL13B regulates IFT-A-mediated retrograde protein trafficking within cilia through its interaction with INPP5E. © 2017. Published by The Company of Biologists Ltd.

  3. Envelope Proteins of White Spot Syndrome Virus (WSSV) Interact with Litopenaeus vannamei Peritrophin-Like Protein (LvPT).

    Science.gov (United States)

    Xie, Shijun; Zhang, Xiaojun; Zhang, Jiquan; Li, Fuhua; Xiang, Jianhai

    2015-01-01

    White spot syndrome virus (WSSV) is a major pathogen in shrimp cultures. The interactions between viral proteins and their receptors on the surface of cells in a frontier target tissue are crucial for triggering an infection. In this study, a yeast two-hybrid (Y2H) library was constructed using cDNA obtained from the stomach and gut of Litopenaeus vannamei, to ascertain the role of envelope proteins in WSSV infection. For this purpose, VP37 was used as the bait in the Y2H library screening. Forty positive clones were detected after screening. The positive clones were analyzed and discriminated, and two clones belonging to the peritrophin family were subsequently confirmed as genuine positive clones. Sequence analysis revealed that both clones could be considered as the same gene, LV-peritrophin (LvPT). Co-immunoprecipitation confirmed the interaction between LvPT and VP37. Further studies in the Y2H system revealed that LvPT could also interact with other WSSV envelope proteins such as VP32, VP38A, VP39B, and VP41A. The distribution of LvPT in tissues revealed that LvPT was mainly expressed in the stomach than in other tissues. In addition, LvPT was found to be a secretory protein, and its chitin-binding ability was also confirmed.

  4. Skeletal muscle morphology, protein synthesis and gene expression in Ehlers Danlos Syndrome

    DEFF Research Database (Denmark)

    Nygaard, Rie H; Jensen, Jacob K; Voermans, Nicol C

    2017-01-01

    INTRODUCTION: Patients with Ehlers Danlos Syndrome are known to have genetically impaired connective tissue and skeletal muscle symptoms in form of pain, fatigue and cramps, however earlier studies have not been able to link these symptoms to morphological muscle changes. METHODS: We obtained...... skeletal muscle biopsies in patients with classic EDS (cEDS, n=5 (Denmark)+ 8 (The Netherlands)) and vascular EDS (vEDS, n=3) and analyzed muscle fiber morphology and content (Western blotting and muscle fiber type/area distributions) and muscle mRNA expression and protein synthesis rate (RT-PCR and stable...... isotope technique). RESULTS: The cEDS patients did not differ from healthy controls (n = 7-11) with regard to muscle fiber type/area, myosin/α-actin ratio, muscle protein synthesis rate or mRNA expression. In contrast, the vEDS patients demonstrated higher expression of matrix proteins compared to c...

  5. Recruitment of bloom-forming cyanobacteria and its driving factors

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... Gao (2005) proposed a hypothesis that a series of processes which were .... mainly peaked in a given time of year before blooms onset. In addition .... Nuisance phytoplankton blooms in coastal, estuaries, and inland waters.

  6. AN OVERVIEW ON BLOOM'S REVISED TAKSONOMY

    OpenAIRE

    TUTKUN, Ömer Faruk

    2013-01-01

    In this study, the main purpose is to present the main frame of revised version in 2001 of Bloom's taxonomy that has been accepted extensively in our country since 1956 as well as around the world. In accordance with this purpose, in the study, answers have been searched to these questions: 1- The rise of the original Bloom's taxonomy and what are the key features of? 2- What are the reasons for renewal of original taxonomy? 3- What kind of arrangements has been made in revised taxonomy? 4- W...

  7. The Severe Acute Respiratory Syndrome (SARS-coronavirus 3a protein may function as a modulator of the trafficking properties of the spike protein

    Directory of Open Access Journals (Sweden)

    Tan Yee-Joo

    2005-02-01

    Full Text Available Abstract Background A recent publication reported that a tyrosine-dependent sorting signal, present in cytoplasmic tail of the spike protein of most coronaviruses, mediates the intracellular retention of the spike protein. This motif is missing from the spike protein of the severe acute respiratory syndrome-coronavirus (SARS-CoV, resulting in high level of surface expression of the spike protein when it is expressed on its own in vitro. Presentation of the hypothesis It has been shown that the severe acute respiratory syndrome-coronavirus genome contains open reading frames that encode for proteins with no homologue in other coronaviruses. One of them is the 3a protein, which is expressed during infection in vitro and in vivo. The 3a protein, which contains a tyrosine-dependent sorting signal in its cytoplasmic domain, is expressed on the cell surface and can undergo internalization. In addition, 3a can bind to the spike protein and through this interaction, it may be able to cause the spike protein to become internalized, resulting in a decrease in its surface expression. Testing the hypothesis The effects of 3a on the internalization of cell surface spike protein can be examined biochemically and the significance of the interplay between these two viral proteins during viral infection can be studied using reverse genetics methodology. Implication of the hypothesis If this hypothesis is proven, it will indicate that the severe acute respiratory syndrome-coronavirus modulates the surface expression of the spike protein via a different mechanism from other coronaviruses. The interaction between 3a and S, which are expressed from separate subgenomic RNA, would be important for controlling the trafficking properties of S. The cell surface expression of S in infected cells significantly impacts viral assembly, viral spread and viral pathogenesis. Modulation by this unique pathway could confer certain advantages during the replication of the severe

  8. Coastal engineering and Harmful Algal Blooms along Alexandria coast, Egypt

    Directory of Open Access Journals (Sweden)

    Amany A. Ismael

    2014-01-01

    The phytoplankton composition and its standing crop became totally different during the two periods. The most important bloom was caused by Micromonas pusilla forming a heavy green tide accompanied by a bloom of Peridinium quinquecorne. Although there were no fish or invertebrate mortality, this bloom caused economic losses to internal tourism. In the absence of any Environmental Assessment, the coastal engineering works increased the harmful algal blooms in Alexandria coastal waters, even after corrective steps were taken to mitigate the harmful effects.

  9. The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA.

    Science.gov (United States)

    Ganapathi, Karthik A; Austin, Karyn M; Lee, Chung-Sheng; Dias, Anusha; Malsch, Maggie M; Reed, Robin; Shimamura, Akiko

    2007-09-01

    Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic dysfunction, and leukemia predisposition. Mutations in the SBDS gene are identified in most patients with SDS. SBDS encodes a highly conserved protein of unknown function. Data from SBDS orthologs suggest that SBDS may play a role in ribosome biogenesis or RNA processing. Human SBDS is enriched in the nucleolus, the major cellular site of ribosome biogenesis. Here we report that SBDS nucleolar localization is dependent on active rRNA transcription. Cells from patients with SDS or Diamond-Blackfan anemia are hypersensitive to low doses of actinomycin D, an inhibitor of rRNA transcription. The addition of wild-type SBDS complements the actinomycin D hypersensitivity of SDS patient cells. SBDS migrates together with the 60S large ribosomal subunit in sucrose gradients and coprecipitates with 28S ribosomal RNA (rRNA). Loss of SBDS is not associated with a discrete block in rRNA maturation or with decreased levels of the 60S ribosomal subunit. SBDS forms a protein complex with nucleophosmin, a multifunctional protein implicated in ribosome biogenesis and leukemogenesis. Our studies support the addition of SDS to the growing list of human bone marrow failure syndromes involving the ribosome.

  10. Posttranslational Protein Modification in the Salivary Glands of Sjögren’s Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Rafael Herrera-Esparza

    2013-01-01

    Full Text Available The present study investigated posttranslational reactions in the salivary glands of patients with Sjögren’s syndrome. We analysed the biopsies of primary Sjögren’s patients using immunohistochemistry and a tag-purified anticyclic citrullinated protein (CCP antibody to detect citrullinated peptides, and the presence of peptidylarginine deiminase 2 (PAD2 was assessed simultaneously. The present work demonstrated the weak presence of the PAD2 enzyme in some normal salivary glands, although PAD2 expression was increased considerably in Sjögren’s patients. The presence of citrullinated proteins was also detected in the salivary tissues of Sjögren’s patients, which strongly supports the in situ posttranslational modification of proteins in this setting. Furthermore, the mutual expression of CCP and PAD2 suggests that this posttranslational modification is enzyme dependent. In conclusion, patients with Sjögren’s syndrome expressed the catalytic machinery to produce posttranslational reactions that may result in autoantigen triggering.

  11. Proteomic Identification of Altered Cerebral Proteins in the Complex Regional Pain Syndrome Animal Model

    Directory of Open Access Journals (Sweden)

    Francis Sahngun Nahm

    2014-01-01

    Full Text Available Background. Complex regional pain syndrome (CRPS is a rare but debilitating pain disorder. Although the exact pathophysiology of CRPS is not fully understood, central and peripheral mechanisms might be involved in the development of this disorder. To reveal the central mechanism of CRPS, we conducted a proteomic analysis of rat cerebrum using the chronic postischemia pain (CPIP model, a novel experimental model of CRPS. Materials and Methods. After generating the CPIP animal model, we performed a proteomic analysis of the rat cerebrum using a multidimensional protein identification technology, and screened the proteins differentially expressed between the CPIP and control groups. Results. A total of 155 proteins were differentially expressed between the CPIP and control groups: 125 increased and 30 decreased; expressions of proteins related to cell signaling, synaptic plasticity, regulation of cell proliferation, and cytoskeletal formation were increased in the CPIP group. However, proenkephalin A, cereblon, and neuroserpin were decreased in CPIP group. Conclusion. Altered expression of cerebral proteins in the CPIP model indicates cerebral involvement in the pathogenesis of CRPS. Further study is required to elucidate the roles of these proteins in the development and maintenance of CRPS.

  12. Algal blooms: a perspective from the coasts of India

    Digital Repository Service at National Institute of Oceanography (India)

    DeSilva, M.S.; Anil, A.C.; Naik, R.K.; DeCosta, P.M.

    Algal blooms have been documented along the west and east coasts of India. A review of bloom occurrences in Indian waters from 1908 to 2009 points out that a total of 101 cases have been reported. A comparison of the bloom cases reported before...

  13. Production and Characterization of Monoclonal Antibodies of Shrimp White Spot Syndrome Virus Envelope Protein VP28

    Institute of Scientific and Technical Information of China (English)

    Wan-gang GU; Jun-fa YUAN; Ge-lin XU; Li-juan LI; Ni LIU; Cong ZHANG; Jian-hong ZHANG; Zheng-li SHI

    2007-01-01

    BALB/c mice were immunized with purified White spot syndrome virus (WSSV).Six monoclonal antibody cell lines were selected by ELISA with VP28 protein expressed in E.coll in vitro neutralization experiments showed that 4 of them could inhibit the virus infection in crayfish.Westernblot suggested that all these monoclonal antibodies were against the conformational structure of VP28.The monoclonal antibody 7B4 was labeled with colloidal gold particles and used to locate the VP28 on virus envelope by immunogold labeling.These monoclonal antibodies could be used to develop immunological diagnosis methods for WSSV infection.

  14. The role of heparin-binding protein in acute respiratory distress syndrome

    Institute of Scientific and Technical Information of China (English)

    刘杨

    2014-01-01

    Objective To study the role of heparin-binding protein(HBP)in sepsis-associated acute respiratory distress syndrome(ARDS),and to evaluate the prognostic value of HBP in ARDS.Methods Sixty seven sepsis patients were enrolled in the prospective study.According to whether present ARDS,patients were divided into two groups:ARDS group and non-ARDS group.Blood samples were obtained within 2 hours after patients were diagnosed with sepsis.We measured the level of interleukin-6,interleukin-8 and HBP by ELISA,counted the

  15. An abundant evolutionarily conserved CSB-PiggyBac fusion protein expressed in Cockayne syndrome.

    Directory of Open Access Journals (Sweden)

    John C Newman

    2008-03-01

    Full Text Available Cockayne syndrome (CS is a devastating progeria most often caused by mutations in the CSB gene encoding a SWI/SNF family chromatin remodeling protein. Although all CSB mutations that cause CS are recessive, the complete absence of CSB protein does not cause CS. In addition, most CSB mutations are located beyond exon 5 and are thought to generate only C-terminally truncated protein fragments. We now show that a domesticated PiggyBac-like transposon PGBD3, residing within intron 5 of the CSB gene, functions as an alternative 3' terminal exon. The alternatively spliced mRNA encodes a novel chimeric protein in which CSB exons 1-5 are joined in frame to the PiggyBac transposase. The resulting CSB-transposase fusion protein is as abundant as CSB protein itself in a variety of human cell lines, and continues to be expressed by primary CS cells in which functional CSB is lost due to mutations beyond exon 5. The CSB-transposase fusion protein has been highly conserved for at least 43 Myr since the divergence of humans and marmoset, and appears to be subject to selective pressure. The human genome contains over 600 nonautonomous PGBD3-related MER85 elements that were dispersed when the PGBD3 transposase was last active at least 37 Mya. Many of these MER85 elements are associated with genes which are involved in neuronal development, and are known to be regulated by CSB. We speculate that the CSB-transposase fusion protein has been conserved for host antitransposon defense, or to modulate gene regulation by MER85 elements, but may cause CS in the absence of functional CSB protein.

  16. Role of mitogen-activated protein kinase pathways in multifactorial adverse cardiac remodeling associated with metabolic syndrome.

    Science.gov (United States)

    Asrih, Mohamed; Mach, François; Nencioni, Alessio; Dallegri, Franco; Quercioli, Alessandra; Montecucco, Fabrizio

    2013-01-01

    Metabolic syndrome has been widely associated with an increased risk for acute cardiovascular events. Emerging evidence supports metabolic syndrome as a condition favoring an adverse cardiac remodeling, which might evolve towards heart dysfunction and failure. This pathological remodeling has been described to result from the cardiac adaptive response to clinical mechanical conditions (such as hypertension, dyslipidemia, and hyperglycemia), soluble inflammatory molecules (such as cytokines and chemokines), as well as hormones (such as insulin), characterizing the pathophysiology of metabolic syndrome. Moreover, these cardiac processes (resulting in cardiac hypertrophy and fibrosis) are also associated with the modulation of intracellular signalling pathways within cardiomyocytes. Amongst the different intracellular kinases, mitogen-activated protein kinases (MAPKs) were shown to be involved in heart damage in metabolic syndrome. However, their role remains controversial. In this paper, we will discuss and update evidence on MAPK-mediated mechanisms underlying cardiac adverse remodeling associated with metabolic syndrome.

  17. Role of Mitogen-Activated Protein Kinase Pathways in Multifactorial Adverse Cardiac Remodeling Associated with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Mohamed Asrih

    2013-01-01

    Full Text Available Metabolic syndrome has been widely associated with an increased risk for acute cardiovascular events. Emerging evidence supports metabolic syndrome as a condition favoring an adverse cardiac remodeling, which might evolve towards heart dysfunction and failure. This pathological remodeling has been described to result from the cardiac adaptive response to clinical mechanical conditions (such as hypertension, dyslipidemia, and hyperglycemia, soluble inflammatory molecules (such as cytokines and chemokines, as well as hormones (such as insulin, characterizing the pathophysiology of metabolic syndrome. Moreover, these cardiac processes (resulting in cardiac hypertrophy and fibrosis are also associated with the modulation of intracellular signalling pathways within cardiomyocytes. Amongst the different intracellular kinases, mitogen-activated protein kinases (MAPKs were shown to be involved in heart damage in metabolic syndrome. However, their role remains controversial. In this paper, we will discuss and update evidence on MAPK-mediated mechanisms underlying cardiac adverse remodeling associated with metabolic syndrome.

  18. 5'-adenosine monophosphate-activated protein kinase and the metabolic syndrome.

    Science.gov (United States)

    Mor, Vijay; Unnikrishnan, M K

    2011-09-01

    Lifestyle changes such as physical inactivity combined with calorie-rich, low-fibre diets have triggered an explosive surge in metabolic syndrome, outlined as a cluster of heart attack risk factors such as insulin resistance, raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. By acting as a master-switch of energy homeostasis and associated pathophysiological phenomena, 5'-adenosine monophosphate-activated protein kinase (AMPK) appears to orchestrate the adaptive physiology of energy deficit, suggesting that the sedentary modern human could be suffering from chronic suboptimal AMPK activation. Addressing individual targets with potent ligands with high specificity may be inappropriate (it has not yielded any molecule superior to the sixty year old metformin) because this strategy cannot address a cluster of interrelated pathologies. However, spices, dietary supplements and nutraceuticals attenuate the multiple symptoms of metabolic syndrome in a collective and perhaps more holistic fashion with fewer adverse events. Natural selection could have favoured races that developed a taste for spices and dietary supplements, most of which are not only antioxidants but also activators of AMPK. The review will outline the various biochemical mechanisms and pathophysiological consequences of AMPK activation involving the cluster of symptoms that embrace metabolic syndrome and beyond. Recent advances that integrate energy homeostasis with a number of overarching metabolic pathways and physiological phenomena, including inflammatory conditions, cell growth and development, malignancy, life span, and even extending into environmental millieu, as in obesity mediated by gut microflora and others will also be outlined.

  19. Identification of defects in the fibrillin gene and protein in individuals with the Marfan syndrome and related disorders.

    OpenAIRE

    Milewicz, D M

    1994-01-01

    The Marfan syndrome is an autosomal dominant disorder with pleiotropic manifestations that involve the cardiovascular, ocular, and skeletal systems. Through a number of investigational approaches, the gene encoding for fibrillin, the FBN1 gene on chromosome 15, has been identified as the defective gene causing the Marfan syndrome. Fibrillin is the large glycoprotein with a repetitive domain structure and is a major protein component of microfibrils, a fibrillar system closely associated with ...

  20. MERUNUT PEMAHAMAN TAKSONOMI BLOOM: SUATU KONTEMPLASI FILOSOFIS

    Directory of Open Access Journals (Sweden)

    Dominikus Tulasi

    2010-09-01

    Full Text Available This article would like to share the use of Bloom's taxonomy as a cognitive framework for teaching-learning process to undertake the way student-centered learning. Related to the curriculum based competence in excellent education, the abstract cognitive in applying Blooms taxonomy is so called scaffolding. We know the taxonomy Bloom is a six-level classification system that uses observed student behavior to infer and absorb the level of cognitive achievement domain. This article surveys thinking within general education and management education, which uses and draws on Bloom's taxonomy, and then describes suggested uses of the taxonomy. The empirical evaluation of its effect on student achievement follows, as do thoughts about ways colleagues might use this tool to empower and motivate students as self-responsible learners in the classroom. The objective is to promote higher order thinking in college students, we understood an effort to learn how to assess critical-thinking skills in an introductory course. It means, we develop a process by which questions are prepared with both content and critical-thinking skills in mind.

  1. Spring bloom onset in the Nordic Seas

    Science.gov (United States)

    Mignot, Alexandre; Ferrari, Raffaele; Mork, Kjell Arne

    2016-06-01

    The North Atlantic spring bloom is a massive annual growth event of marine phytoplankton, tiny free-floating algae that form the base of the ocean's food web and generates a large fraction of the global primary production of organic matter. The conditions that trigger the onset of the spring bloom in the Nordic Seas, at the northern edge of the North Atlantic, are studied using in situ data from six bio-optical floats released north of the Arctic Circle. It is often assumed that spring blooms start as soon as phytoplankton cells daily irradiance is sufficiently abundant that division rates exceed losses. The bio-optical float data instead suggest the tantalizing hypothesis that Nordic Seas blooms start when the photoperiod, the number of daily light hours experienced by phytoplankton, exceeds a critical value, independently of division rates. The photoperiod trigger may have developed at high latitudes where photosynthesis is impossible during polar nights and phytoplankton enters into a dormant stage in winter. While the first accumulation of biomass recorded by the bio-optical floats is consistent with the photoperiod hypothesis, it is possible that some biomass accumulation started before the critical photoperiod but at levels too low to be detected by the fluorometers. More precise observations are needed to test the photoperiod hypothesis.

  2. Harmful cyanobacterial blooms: causes, consequences, and controls.

    Science.gov (United States)

    Paerl, Hans W; Otten, Timothy G

    2013-05-01

    Cyanobacteria are the Earth's oldest oxygenic photoautotrophs and have had major impacts on shaping its biosphere. Their long evolutionary history (≈ 3.5 by) has enabled them to adapt to geochemical and climatic changes, and more recently anthropogenic modifications of aquatic environments, including nutrient over-enrichment (eutrophication), water diversions, withdrawals, and salinization. Many cyanobacterial genera exhibit optimal growth rates and bloom potentials at relatively high water temperatures; hence global warming plays a key role in their expansion and persistence. Bloom-forming cyanobacterial taxa can be harmful from environmental, organismal, and human health perspectives by outcompeting beneficial phytoplankton, depleting oxygen upon bloom senescence, and producing a variety of toxic secondary metabolites (e.g., cyanotoxins). How environmental factors impact cyanotoxin production is the subject of ongoing research, but nutrient (N, P and trace metals) supply rates, light, temperature, oxidative stressors, interactions with other biota (bacteria, viruses and animal grazers), and most likely, the combined effects of these factors are all involved. Accordingly, strategies aimed at controlling and mitigating harmful blooms have focused on manipulating these dynamic factors. The applicability and feasibility of various controls and management approaches is discussed for natural waters and drinking water supplies. Strategies based on physical, chemical, and biological manipulations of specific factors show promise; however, a key underlying approach that should be considered in almost all instances is nutrient (both N and P) input reductions; which have been shown to effectively reduce cyanobacterial biomass, and therefore limit health risks and frequencies of hypoxic events.

  3. In the Cells of the 'Bloom Taxonomy'.

    Science.gov (United States)

    Calder, J. R.

    1983-01-01

    The Bloom Taxonomy of Educational Objectives is criticized because its distinctions between cognitive, affective, and psychomotor domains are invalid; its categories are ill-defined and do not denote homogenous types of objectives; its structural base is inconsistent; and it is debatable whether it is a true taxonomy. (IS)

  4. Biology in Bloom: Implementing Bloom's Taxonomy to Enhance Student Learning in Biology

    OpenAIRE

    Crowe, Alison; Dirks, Clarissa; Wenderoth, Mary Pat

    2008-01-01

    We developed the Blooming Biology Tool (BBT), an assessment tool based on Bloom's Taxonomy, to assist science faculty in better aligning their assessments with their teaching activities and to help students enhance their study skills and metacognition. The work presented here shows how assessment tools, such as the BBT, can be used to guide and enhance teaching and student learning in a discipline-specific manner in postsecondary education. The BBT was first designed and extensively tested fo...

  5. Soy Germ Protein With or Without-Zn Improve Plasma Lipid Profile in Metabolic Syndrome Women

    Directory of Open Access Journals (Sweden)

    SIWI PRAMATAMA MARS WIJAYANTI

    2012-03-01

    Full Text Available The aim of this research was to determine the effect of soy germ protein on lipid profile of metabolic syndrome (MetS patients. Respondents were 30 women with criteria, i.e. blood glucose level > normal, body mass index > 25 kg/m2, hypertriglyceridemia, low cholesterol-HDL level, 40-65 years old, living in Purwokerto, and signed the informed consent. The project was approved by the ethics committee of the Medical Faculty from Gadjah Mada University-Yogyakarta. Respondents were divided into three randomly chosen groups consisting of ten women each. The first, second, and third groups were treated, respectively, with milk enriched soy germ protein plus Zn, milk enriched soy germ protein (without Zn, and placebo for two months. Blood samples were taken at baseline, one and two months after observation. Two months after observation the groups consuming milk enriched with soy germ protein, both with or without Zn, had their level of cholesterol-total decrease from 215.8 to 180.2 mg/dl (P = 0.03, triglyceride from 240.2 to 162.5 mg/dl (P = 0.02, and LDL from 154.01 to 93.85 mg/dl (P = 0.03. In contrast, HDL increased from 38.91 to 49.49 mg/dl (P = 0.0008. In conclusion, soy germ protein can improve lipid profile, thus it can inhibit atherosclerosis incident.

  6. Expression of SET Protein in the Ovaries of Patients with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Xu Boqun

    2013-01-01

    Full Text Available Background. We previously found that expression of SET gene was up-regulated in polycystic ovaries by using microarray. It suggested that SET may be an attractive candidate regulator involved in the pathophysiology of polycystic ovary syndrome (PCOS. In this study, expression and cellular localization of SET protein were investigated in human polycystic and normal ovaries. Method. Ovarian tissues, six normal ovaries and six polycystic ovaries, were collected during transsexual operation and surgical treatment with the signed consent form. The cellular localization of SET protein was observed by immunohistochemistry. The expression levels of SET protein were analyzed by Western Blot. Result. SET protein was expressed predominantly in the theca cells and oocytes of human ovarian follicles in both PCOS ovarian tissues and normal ovarian tissues. The level of SET protein expression in polycystic ovaries was triple higher than that in normal ovaries (P<0.05. Conclusion. SET was overexpressed in polycystic ovaries more than that in normal ovaries. Combined with its localization in theca cells, SET may participate in regulating ovarian androgen biosynthesis and the pathophysiology of hyperandrogenism in PCOS.

  7. Increased levels of tau-like protein in patients with Down syndrome.

    Science.gov (United States)

    Mehta, P D; Patrick, B A; Dalton, A J; Aisen, P S; Emmerling, M E; Sersen, E A; Wisniewski, H M

    1999-11-19

    Tau-like protein levels from 40 Down syndrome (DS) persons (31-70 years old), 40 non-DS age-matched normal controls, 18 non-DS mentally retarded (MR) persons (26-91 years old), 25 probable Alzheimer disease (AD) patients (55-99 years old) and 24 non-demented elderly controls (54-79 years old) were measured using a sandwich enzyme linked immunosorbent assay. The levels were detected in 22 of 40 DS persons and were significantly higher in DS than any other group (P < 0.0001). There was no relationship between tau-like protein levels and age, gender or apolipoprotein E phenotypes in any of the five groups.

  8. Subsurface phytoplankton blooms fuel pelagic production in the North Sea

    DEFF Research Database (Denmark)

    Richardson, Kathrine; Visser, Andre; Pedersen, Flemming

    2000-01-01

    convincingly that energy fixed during the spring bloom is fueling the pelagic production occurring during summer months. We argue here that periodic phytoplankton blooms are occurring during the summer in the North Sea at depths of >25 m and that the accumulated new production [sensu (Dugdale and Goering......, Limnol. Oceanogr., 12, 196-206, 1967)] occurring in these blooms may be greater than that occurring in the spring bloom in the same regions. Thus, such blooms may explain apparent discrepancies in production yields between different temperate marine systems...

  9. Potential protein biomarkers for burning mouth syndrome discovered by quantitative proteomics

    Science.gov (United States)

    Ji, Eoon Hye; Diep, Cynthia; Liu, Tong; Li, Hong; Merrill, Robert; Messadi, Diana

    2017-01-01

    Burning mouth syndrome (BMS) is a chronic pain disorder characterized by severe burning sensation in normal looking oral mucosa. Diagnosis of BMS remains to be a challenge to oral healthcare professionals because the method for definite diagnosis is still uncertain. In this study, a quantitative saliva proteomic analysis was performed in order to identify target proteins in BMS patients’ saliva that may be used as biomarkers for simple, non-invasive detection of the disease. By using isobaric tags for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry to quantify 1130 saliva proteins between BMS patients and healthy control subjects, we found that 50 proteins were significantly changed in the BMS patients when compared to the healthy control subjects (p ≤ 0.05, 39 up-regulated and 11 down-regulated). Four candidates, alpha-enolase, interleukin-18 (IL-18), kallikrein-13 (KLK13), and cathepsin G, were selected for further validation. Based on enzyme-linked immunosorbent assay measurements, three potential biomarkers, alpha-enolase, IL-18, and KLK13, were successfully validated. The fold changes for alpha-enolase, IL-18, and KLK13 were determined as 3.6, 2.9, and 2.2 (burning mouth syndrome vs. control), and corresponding receiver operating characteristic values were determined as 0.78, 0.83, and 0.68, respectively. Our findings indicate that testing of the identified protein biomarkers in saliva might be a valuable clinical tool for BMS detection. Further validation studies of the identified biomarkers or additional candidate biomarkers are needed to achieve a multi-marker prediction model for improved detection of BMS with high sensitivity and specificity.

  10. Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome.

    Science.gov (United States)

    Ü Basmanav, F Buket; Cau, Laura; Tafazzoli, Aylar; Méchin, Marie-Claire; Wolf, Sabrina; Romano, Maria Teresa; Valentin, Frederic; Wiegmann, Henning; Huchenq, Anne; Kandil, Rima; Garcia Bartels, Natalie; Kilic, Arzu; George, Susannah; Ralser, Damian J; Bergner, Stefan; Ferguson, David J P; Oprisoreanu, Ana-Maria; Wehner, Maria; Thiele, Holger; Altmüller, Janine; Nürnberg, Peter; Swan, Daniel; Houniet, Darren; Büchner, Aline; Weibel, Lisa; Wagner, Nicola; Grimalt, Ramon; Bygum, Anette; Serre, Guy; Blume-Peytavi, Ulrike; Sprecher, Eli; Schoch, Susanne; Oji, Vinzenz; Hamm, Henning; Farrant, Paul; Simon, Michel; Betz, Regina C

    2016-12-01

    Uncombable hair syndrome (UHS), also known as "spun glass hair syndrome," "pili trianguli et canaliculi," or "cheveux incoiffables" is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Until now, both simplex and familial UHS-affected case subjects with autosomal-dominant as well as -recessive inheritance have been reported. However, none of these case subjects were linked to a molecular genetic cause. Here, we report the identification of UHS-causative mutations located in the three genes PADI3 (peptidylarginine deiminase 3), TGM3 (transglutaminase 3), and TCHH (trichohyalin) in a total of 11 children. All of these individuals carry homozygous or compound heterozygous mutations in one of these three genes, indicating an autosomal-recessive inheritance pattern in the majority of UHS case subjects. The two enzymes PADI3 and TGM3, responsible for posttranslational protein modifications, and their target structural protein TCHH are all involved in hair shaft formation. Elucidation of the molecular outcomes of the disease-causing mutations by cell culture experiments and tridimensional protein models demonstrated clear differences in the structural organization and activity of mutant and wild-type proteins. Scanning electron microscopy observations revealed morphological alterations in hair coat of Padi3 knockout mice. All together, these findings elucidate the molecular genetic causes of UHS and shed light on its pathophysiology and hair physiology in general. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  11. The Fowler syndrome-associated protein FLVCR2 is an importer of heme.

    Science.gov (United States)

    Duffy, Simon P; Shing, Jennifer; Saraon, Punit; Berger, Lloyd C; Eiden, Maribeth V; Wilde, Andrew; Tailor, Chetankumar S

    2010-11-01

    Mutations in FLVCR2, a cell surface protein related by homology and membrane topology to the heme exporter/retroviral receptor FLVCR1, have recently been associated with Fowler syndrome, a vascular disorder of the brain. We previously identified FLVCR2 to function as a receptor for FY981 feline leukemia virus (FeLV). However, the cellular function of FLVCR2 remains unresolved. Here, we report the cellular function of FLVCR2 as an importer of heme, based on the following observations. First, FLVCR2 binds to hemin-conjugated agarose, and binding is competed by free hemin. Second, mammalian cells and Xenopus laevis oocytes expressing FLVCR2 display enhanced heme uptake. Third, heme import is reduced after the expression of FLVCR2-specific small interfering RNA (siRNA) or after the binding of the FY981 FeLV envelope protein to the FLVCR2 receptor. Finally, cells overexpressing FLVCR2 are more sensitive to heme toxicity, a finding most likely attributable to enhanced heme uptake. Tissue expression analysis indicates that FLVCR2 is expressed in a broad range of human tissues, including liver, placenta, brain, and kidney. The identification of a cellular function for FLVCR2 will have important implications in elucidating the pathogenic mechanisms of Fowler syndrome and of phenotypically associated disorders.

  12. WRN protein as a novel erythroblast immunohistochemical marker with applications for the diagnosis of Werner syndrome.

    Science.gov (United States)

    Sadahira, Yoshito; Sugihara, Takashi; Fujiwara, Hideyo; Nishimura, Hirotake; Suetsugu, Yoshimasa; Takeshita, Morishige; Okamura, Seiichi; Goto, Makoto

    2015-03-01

    Genetic testing for mutations in the WRN gene is critical for the diagnosis of Werner syndrome (WS); however, these tests cannot be performed in a clinical setting. Nearly all of the WRN mutations result in expression of truncated WRN proteins that are missing the C-terminal nuclear localization signal. We evaluated the use of WRN protein immunohistochemistry for diagnosing WS using paraffin-embedded bone marrow sections. Using a well-defined commercially available polyclonal antibody against the C terminus of WRN, we found that of all the cell types tested, bone marrow erythroid precursors showed the strongest nuclear expression of WRN. Immunohistochemical analysis of bone marrow samples from 120 patients with non-WS hematological disorders (age range, 7 days-90 years) revealed WRN staining of the nuclei of CD71-positive early and late erythroid precursors. Erythroblasts negative for WRN immunostaining were only observed in two patients, both of whom were diagnosed with WS: one with concomitant myelodysplastic syndrome and the other with erythroleukemia with overexpression of TP53. Western blot analysis and immunocytochemistry indicated WRN was localized in the nuclei of the four positive control cell lines from non-WS patients but not in the five cell lines from WS patients, who had three different types of WRN mutations. Thus, immunohistochemical detection of WRN in erythroblasts from bone marrow paraffin sections could be useful in screening of WS cases and worthy of further molecular confirmation.

  13. Peritoneal protein losses in children with steroid-resistant nephrotic syndrome on continuous-cycler peritoneal dialysis.

    Science.gov (United States)

    Kopanati, Sashikala; Baum, Michel; Quan, Albert

    2006-07-01

    Glomerular protein permeability rises in nephrotic syndrome and may result from the effect of an unidentified "circulating factor." The effect of this "circulating factor" on the permeability of other body membranes is unknown. In this study we examine the peritoneal membrane protein permeability in patients with nephrotic syndrome on chronic-cycler peritoneal dialysis. We conducted a retrospective study of peritoneal protein losses in the dialysate effluent of 60 pediatric peritoneal dialysis patients (ages 5.1-22 years) over a 6-year period (January 1997-December 2002). Nineteen patients had steroid-resistant nephrotic syndrome (SRNS), while 41 had other non-nephrotic etiologies of renal failure. Total and normalized peritoneal protein losses are higher in SRNS than in non-nephrotic patients (12,603+/-5,403 mg/day vs 4,475+/-469 mg/day, Ppermeability, was higher in SRNS patients (3.50+/-1.00% vs 0.68+/-0.06%, Pdialysis, dialysis prescription, numbers of peritonitis episodes, catheter replacements, or hospitalizations. In summary, these results demonstrate that peritoneal protein losses in patients with SRNS are twice as great as in those without nephrotic syndrome. These results are consistent with the systemic effect of a "circulating factor" in SRNS and underscore the importance of adequate protein intake in patients on peritoneal dialysis.

  14. Insulin-like growth factor-I and insulin-like growth factor-binding proteins in the nephrotic syndrome.

    Science.gov (United States)

    Feld, S M; Hirschberg, R

    1996-06-01

    Similar to findings in the nephrotic syndrome in humans, rats with the doxorubicin-induced nephrotic syndrome (which resembles minimal change disease) have reduced serum levels of insulin-like growth factor-I (IGF-I). This is mainly caused by glomerular ultrafiltration of IGF-I-containing binding protein complexes, primarily of a molecular weight of approximately 50 kilodaltons, and urinary losses of the peptide. Despite urinary excretion of IGF-binding protein (IGFBP)-2, serum levels are increased more than twofold in the nephrotic syndrome compared with controls, because of increased synthesis of this binding protein by the liver. In contrast, the liver synthesis of IGFBP-3, the predominant binding protein in normal serum, is unchanged in the nephrotic syndrome. However, binding and serum levels of IGFBP-3 are reduced in nephrotic rat serum, apparently due to proteolytic degradation of IGFBP-3. The glomerular ultrafiltration of IGF-I, which leads to biologically significant IGF-I concentrations of about 1.35 nM in proximal tubule fluid, may have metabolic consequences, such as increased tubular phosphate absorption. Hypothetically, tubule fluid IGF-I may also contribute to progressive tubulointerstitial fibrosis which is sometimes present in protractive nephrotic glomerulopathies. The profound changes in the IGF-I/IGFBP system in the nephrotic syndrome may also contribute to systemic metabolic abnormalities and growth failure.

  15. The Role of Heat Shock Protein 90B1 in Patients with Polycystic Ovary Syndrome.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available Polycystic ovary syndrome (PCOS is a heterogenetic disorder in women that is characterized by arrested follicular growth and anovulatory infertility. The altered protein expression levels in the ovarian tissues reflect the molecular defects in folliculogenesis. To identify aberrant protein expression in PCOS, we analyzed protein expression profiles in the ovarian tissues of patients with PCOS. We identified a total of 18 protein spots that were differentially expressed in PCOS compared with healthy ovarian samples. A total of 13 proteins were upregulated and 5 proteins were downregulated. The expression levels of heat shock protein 90B1 (HSP90B1 and calcium signaling activator calmodulin 1 (CALM1 were increased by at least two-fold. The expression levels of HSP90B1 and CALM1 were positively associated with ovarian cell survival and negatively associated with caspase-3 activation and apoptosis. Knock-down of HSP90B1 with siRNA attenuated ovarian cell survival and increased apoptosis. In contrast, ovarian cell survival was improved and cell apoptosis was decreased in cells over-expressing HSP90B1. These results demonstrated the pivotal role of HSP90B1 in the proliferation and survival of ovarian cells, suggesting a critical role for HSP90B1 in the pathogenesis of PCOS. We also observed a downregulation of anti-inflammatory activity-related annexin A6 (ANXA6 and tropomyosin 2 (TPM2 compared with the normal controls, which could affect cell division and folliculogenesis in PCOS. This is the first study to identify novel altered gene expression in the ovarian tissues of patients with PCOS. These findings may have significant implications for future diagnostic and treatment strategies for PCOS using molecular interventions.

  16. The Role of Heat Shock Protein 90B1 in Patients with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Li, Li; Mo, Hui; Zhang, Jing; Zhou, Yongxian; Peng, Xiuhong; Luo, Xiping

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a heterogenetic disorder in women that is characterized by arrested follicular growth and anovulatory infertility. The altered protein expression levels in the ovarian tissues reflect the molecular defects in folliculogenesis. To identify aberrant protein expression in PCOS, we analyzed protein expression profiles in the ovarian tissues of patients with PCOS. We identified a total of 18 protein spots that were differentially expressed in PCOS compared with healthy ovarian samples. A total of 13 proteins were upregulated and 5 proteins were downregulated. The expression levels of heat shock protein 90B1 (HSP90B1) and calcium signaling activator calmodulin 1 (CALM1) were increased by at least two-fold. The expression levels of HSP90B1 and CALM1 were positively associated with ovarian cell survival and negatively associated with caspase-3 activation and apoptosis. Knock-down of HSP90B1 with siRNA attenuated ovarian cell survival and increased apoptosis. In contrast, ovarian cell survival was improved and cell apoptosis was decreased in cells over-expressing HSP90B1. These results demonstrated the pivotal role of HSP90B1 in the proliferation and survival of ovarian cells, suggesting a critical role for HSP90B1 in the pathogenesis of PCOS. We also observed a downregulation of anti-inflammatory activity-related annexin A6 (ANXA6) and tropomyosin 2 (TPM2) compared with the normal controls, which could affect cell division and folliculogenesis in PCOS. This is the first study to identify novel altered gene expression in the ovarian tissues of patients with PCOS. These findings may have significant implications for future diagnostic and treatment strategies for PCOS using molecular interventions.

  17. Gamma glutamyltransferase levels and its association with high sensitive C-reactive protein in patients with acute coronary syndromes

    Science.gov (United States)

    Emiroglu, Mehmet Yunus; Esen, Özlem Batukan; Bulut, Mustafa; Karapinar, Hekim; Kaya, Zekeriya; Akcakoyun, Mustafa; Kargin, Ramazan; Aung, Soe Moe; Alızade, Elnur; Pala, Selcuk; Esen, Ali Metin

    2010-01-01

    Background: Elevated Gamma-glutamyltransferase (GGT) level is independently correlated with conditions associatedwith increased atherosclerosis, such as obesity, elevated serum cholesterol, high blood pressure and myocardial infarction. It is also demonstrated that serum gamma-glutamyltransferase activity is an independent risk factor for myocardial infarction and cardiac death in patients with coronary artery disease. Although the relationship between gamma-glutamyltransferase and coronary artery disease has been reported, not many studies have shown the relationship between changes ofgamma-glutamyltransferase in acute coronary syndromes and a well established coronary risk factor high sensitive C-reactive protein. (hs-CRP). Aims: In this study, how gamma-glutamyltransferase levels changed in acute coronary syndromes and its relationship with high sensitive C-reactive protein if any were studied. Patients & Methods: This trial was carried out at Kosuyolu Cardiovascular Training and Research Hospital and Van Yuksek Ihtisas Hospital, Turkey. 219 patients (177 males and 42 females) presenting with acute coronary syndrome, and 51 control subjects between September 2007 and September 2008 were included in the study. Serum gamma-glutamyltransferase, high sensitive C-reactive protein, serum lipoprotein levels and troponin I were determined. Results: Serum gamma-glutamyltransferase and high sensitive C-reactive protein levels were higher in acute coronary syndrome patients compared to control. There was also correlation between gamma-glutamyltransferase and high sensitive C-reactive protein levels. Conclusion: Serum gamma-glutamyltransferase and high sensitive C-reactive protein levels were higher in acute coronary syndrome patients. In subgroup analyses, the higher difference with Non-ST elevation myocardial infarction and ST elevation myocardial infarction groups than unstable angina oectoris group proposes a relationship between gamma-glutamyltransferase and severity

  18. Gamma glutamyltransferase levels and its association with high sensitive C-reactive protein in patients with acute coronary syndromes

    Directory of Open Access Journals (Sweden)

    Mehmet Yunus Emiroglu

    2010-07-01

    Full Text Available Background: Elevated Gamma-glutamyltransferase (GGT level is independently correlated with conditions associatedwith increased atherosclerosis, such as obesity, elevated serum cholesterol, high blood pressure and myocardial infarction. It is also demonstrated that serum gamma-glutamyltransferase activity is an independent risk factor for myocardial infarction and cardiac death in patients with coronary artery disease. Although the relationship between gamma-glutamyltransferase and coronary artery disease has been reported, not many studies have shown the relationship between changes ofgamma-glutamyltransferase in acute coronary syndromes and a well established coronary risk factor high sensitive C-reactive protein. (hs-CRP. Aims: In this study, how gamma-glutamyltransferase levels changed in acute coronary syndromes and its relationship with high sensitive C-reactive protein if any were studied. Patients & Methods:This trial was carried out at Kosuyolu Cardiovascular Training and Research Hospital and Van Yuksek Ihtisas Hospital, Turkey. 219 patients (177 males and 42 females presenting with acute coronary syndrome, and 51 control subjects between September 2007 and September 2008 were included in the study. Serum gamma-glutamyltransferase, high sensitive C-reactive protein, serum lipoprotein levels and troponin I were determined. Results: Serum gamma-glutamyltransferase and high sensitive C-reactive protein levels were higher in acute coronary syndrome patients compared to control. There was also correlation between gamma-glutamyltransferase and high sensitive C-reactive protein levels. Conclusion: Serum gamma-glutamyltransferase and high sensitive C-reactive protein levels were higher in acute coronary syndrome patients. In subgroup analyses, the higher difference with Non-ST elevation myocardial infarction and ST elevation myocardial infarction groups than unstable angina oectoris group proposes a relationship between gamma

  19. Gamma glutamyltransferase levels and its association with high sensitive C-reactive protein in patients with acute coronary syndromes

    Directory of Open Access Journals (Sweden)

    Mehmet Yunus Emiroglu

    2010-01-01

    Full Text Available Background: Elevated Gamma-glutamyltransferase (GGT level is independently correlated with conditions associatedwith increased atherosclerosis, such as obesity, elevated serum cholesterol, high blood pressure and myocardial infarction. It is also demonstrated that serum gamma-glutamyltransferase activity is an independent risk factor for myocardial infarction and cardiac death in patients with coronary artery disease. Although the relationship between gamma-glutamyltransferase and coronary artery disease has been reported, not many studies have shown the relationship between changes ofgamma-glutamyltransferase in acute coronary syndromes and a well established coronary risk factor high sensitive C-reactive protein. (hs-CRP. Aims: In this study, how gamma-glutamyltransferase levels changed in acute coronary syndromes and its relationship with high sensitive C-reactive protein if any were studied. Patients & Methods: This trial was carried out at Kosuyolu Cardiovascular Training and Research Hospital and Van Yuksek Ihtisas Hospital, Turkey. 219 patients (177 males and 42 females presenting with acute coronary syndrome, and 51 control subjects between September 2007 and September 2008 were included in the study. Serum gamma-glutamyltransferase, high sensitive C-reactive protein, serum lipoprotein levels and troponin I were determined. Results: Serum gamma-glutamyltransferase and high sensitive C-reactive protein levels were higher in acute coronary syndrome patients compared to control. There was also correlation between gamma-glutamyltransferase and high sensitive C-reactive protein levels. Conclusion: Serum gamma-glutamyltransferase and high sensitive C-reactive protein levels were higher in acute coronary syndrome patients. In subgroup analyses, the higher difference with Non-ST elevation myocardial infarction and ST elevation myocardial infarction groups than unstable angina oectoris group proposes a relationship between gamma

  20. A genetic screen for components of the mammalian RNA interference pathway in Bloom-deficient mouse embryonic stem cells.

    Science.gov (United States)

    Trombly, Melanie I; Su, Hong; Wang, Xiaozhong

    2009-03-01

    Genetic screens performed in model organisms have helped identify key components of the RNA interference (RNAi) pathway. Recessive genetic screens have recently become feasible through the use of mouse embryonic stem (ES) cells that are Bloom's syndrome protein (Blm) deficient. Here, we developed and performed a recessive genetic screen to identify components of the mammalian RNAi pathway in Blm-deficient ES cells. Genome-wide mutagenesis using a retroviral gene trap strategy resulted in the isolation of putative homozygous RNAi mutant cells. Candidate clones were confirmed by an independent RNAi-based reporter assay and the causative gene trap integration site was identified using molecular techniques. Our screen identified multiple mutant cell lines of Argonaute 2 (Ago2), a known essential component of the RNAi pathway. This result demonstrates that true RNAi components can be isolated by this screening strategy. Furthermore, Ago2 homozygous mutant ES cells provide a null genetic background to perform mutational analyses of the Ago2 protein. Using genetic rescue, we resolve an important controversy regarding the role of two phenylalanine residues in Ago2 activity.

  1. Wind-driven marine phytoplank blooms: Satellite observation and analysis

    Science.gov (United States)

    Tang, DanLing

    2016-07-01

    Algal bloom is defined as a rapid increase or accumulation in biomass in an aquatic system. It not only can increase the primary production but also could result in negative ecological consequence, e.g.,Harmful Algal Blooms (HABs). According to the classic theory for the formation of algal blooms "critical depth" and "eutrophication", oligotrophic sea area is usually difficult to form a large area of algal blooms, and actuallythe traditional observation is only sporadic capture to the existence of algal blooms.Taking full advantage of multiple data of satellite remote sensing , this study introduces "Wind-driven algal blooms in open oceans: observation and mechanisms" It explained except classic coastal Ekman transport, the wind through a variety of mechanisms affecting the formation of algal blooms. Proposed a conceptual model of "Strong wind -upwelling-nutrient-phytoplankton blooms" in Western South China Sea (SCS) to assess role of wind-induced advection transport in phytoplankton bloom formation. It illustrates the nutrient resources that support long-term offshore phytoplankton blooms in the western SCS; (2)Proposal of the theory that "typhoons cause vertical mixing, induce phytoplankton blooms", and quantify their important contribution to marine primary production; Proposal a new ecological index for typhoon. Proposed remote sensing inversion models. (3)Finding of the spatial and temporaldistributions pattern of harmful algal bloom (HAB)and species variations of HAB in the South Yellow Sea and East China Sea, and in the Pearl River estuary, and their oceanic dynamic mechanisms related with monsoon; The project developed new techniques and generated new knowledge, which significantly improved understanding of the formation mechanisms of algal blooms. The proposed "wind-pump" mechanism integrates theoretical system combined "ocean dynamics, development of algal blooms, and impact on primary production", which will benefit fisheries management. These

  2. White spot syndrome virus envelope protein VP124 involved in the virus infection

    Institute of Scientific and Technical Information of China (English)

    ZHU Yanbing; WU Chenglin; YANG Feng

    2008-01-01

    White spot syndrome virus(WSSV)is one of the major shrimp pathogens causing large economic losses to shrimp farming.In an attempt to identify the envelope proteins involved in the virus infection,purified WSSV virions were mixed with three antisera against WSSV envelope proteins(VP39,VP124 and VP187),individually.And then they were injected intramuscularly into crayfish (Procambarus clarkii) to conduct in vivo neutralization assays.The results showed that for groups injected with virions only and groups injected with the mixture of virions and antiserum against VP124,the crayfish mortalities were 100% and 60% on the 8th day postinfection,individually.The virus infection could be delayed or neutralized by antibody against the envelope pro-tein VP124.Quantitative PCR was used to further investigate the influence of three antisera described above on the virus infec-tion.The results showed that the antiserum against VP124 could restrain the propagation of WSSV in crayfish.All of the results suggested that the viral envelope protein VP124 played a role in WSSV infection.

  3. Elements That Regulate the DNA Damage Response of Proteins Defective in Cockayne Syndrome.

    Science.gov (United States)

    Iyama, Teruaki; Wilson, David M

    2016-01-16

    Cockayne syndrome (CS) is a premature aging disorder characterized by developmental defects, multisystem progressive degeneration and sensitivity to ultraviolet light. CS is divided into two primary complementation groups, A and B, with the CSA and CSB proteins presumably functioning in DNA repair and transcription. Using laser microirradiation and confocal microscopy, we characterized the nature and regulation of the CS protein response to oxidative DNA damage, double-strand breaks (DSBs), angelicin monoadducts and trioxsalen interstrand crosslinks (ICLs). Our data indicate that CSB recruitment is influenced by the type of DNA damage and is most rapid and robust as follows: ICLs>DSBs>monoadducts>oxidative lesions. Transcription inhibition reduced accumulation of CSB at sites of monoadducts and ICLs, but it did not affect recruitment to (although slightly affected retention at) oxidative damage. Inhibition of histone deacetylation altered the dynamics of CSB assembly, suggesting a role for chromatin status in the response to DNA damage, whereas the proteasome inhibitor MG132 had no effect. The C-terminus of CSB and, in particular, its ubiquitin-binding domain were critical to recruitment, while the N-terminus and a functional ATPase domain played a minor role at best in facilitating protein accumulation. Although the absence of CSA had no effect on CSB recruitment, CSA itself localized at sites of ICLs, DSBs and monoadducts but not at oxidative lesions. Our results reveal molecular components of the CS protein response and point to a major involvement of complex lesions in the pathology of CS.

  4. Siderophores: The special ingredient to cyanobacterial blooms

    Science.gov (United States)

    Du, Xue; Creed, Irena; Trick, Charles

    2013-04-01

    Freshwater lakes provide a number of significant ecological services including clean drinking water, habitat for aquatic biota, and economic benefits. The provision of these ecological services, as well as the health of these aquatic systems, is threatened by the excessive growth of algae, specifically, cyanobacteria. Historically, blooms have been linked to eutrophication but recent occurrences indicate that there are less dramatic changes that induce these blooms. Iron is an essential micronutrient required for specific essential metabolic pathways; however, the amount of biologically available iron in naturally occurring lake ranges from saturation to much lower than cell transport affinities. To assist in the modulation of iron availabilities, cyanobacteria in culture produce low molecular weight compounds that function in an iron binding and acquisition system; nevertheless, this has yet to be confirmed in naturally occurring lakes. This project explored the relationship of P, N and in particular, Fe, in the promotion of cyanobacteria harmful algal blooms in 30 natural freshwater lakes located in and around the Elk Island National Park, Alberta. It is hypothesized that cyanobacteria produce and utilize iron chelators called siderophores in low Fe and nitrogen (N) conditions, creating a competitive advantage over other algae in freshwater lakes. Lakes were selected to represent a range of iron availability to explore the nutrient composition of lakes that propagated cyanobacteria harmful algal blooms (cHABs) compared to lakes that did not. Lake water was analyzed for nutrients, microbial composition, siderophore concentration, and toxin concentration. Modifications were made to optimize the Czaky and Arnow tests for hydroxamate- and catecholate-type siderophores, respectively, for field conditions. Preliminary results indicate the presence of iron-binding ligands (0.11-2.34 mg/L) in freshwater lakes characterized by widely ranging Fe regimes (0.04-2.74 mg

  5. Schwangerschafts Protein 1 (SP1) adds little to the age-related detection of fetal Down syndrome in the first trimester of pregnancy

    NARCIS (Netherlands)

    Kornman, LH; Morssink, LP; Ten Hoor, KA; De Wolf, BTHM; Kloosterman, MD; Beekhuis, [No Value; Mantingh, A

    1998-01-01

    Schwangerschafts Protein 1 (SP1), being a placental protein appearing in the maternal circulation early in pregnancy, has been investigated as a potential marker for Down syndrome in the first trimester. Our study compared SP1 levels in 15 pregnancies with a Down syndrome fetus and 97 matched contro

  6. Schwangerschafts Protein 1 (SP1) adds little to the age-related detection of fetal Down syndrome in the first trimester of pregnancy

    NARCIS (Netherlands)

    Kornman, LH; Morssink, LP; Ten Hoor, KA; De Wolf, BTHM; Kloosterman, MD; Beekhuis, [No Value; Mantingh, A

    1998-01-01

    Schwangerschafts Protein 1 (SP1), being a placental protein appearing in the maternal circulation early in pregnancy, has been investigated as a potential marker for Down syndrome in the first trimester. Our study compared SP1 levels in 15 pregnancies with a Down syndrome fetus and 97 matched

  7. Mutations of the CEP290 gene encoding a centrosomal protein cause Meckel-Gruber syndrome.

    Science.gov (United States)

    Frank, Valeska; den Hollander, Anneke I; Brüchle, Nadina Ortiz; Zonneveld, Marijke N; Nürnberg, Gudrun; Becker, Christian; Du Bois, Gabriele; Kendziorra, Heide; Roosing, Susanne; Senderek, Jan; Nürnberg, Peter; Cremers, Frans P M; Zerres, Klaus; Bergmann, Carsten

    2008-01-01

    Meckel-Gruber syndrome (MKS) is an autosomal recessive, lethal multisystemic disorder characterized by meningooccipital encephalocele, cystic kidney dysplasia, hepatobiliary ductal plate malformation, and postaxial polydactyly. Recently, genes for MKS1 and MKS3 were identified, putting MKS on the list of ciliary disorders (ciliopathies). By positional cloning in a distantly related multiplex family, we mapped a novel locus for MKS to a 3-Mb interval on 12q21. Sequencing of the CEP290 gene located in the minimal critical region showed a homozygous 1-bp deletion supposed to lead to loss of function of the encoded centrosomal protein CEP290/nephrocystin-6. CEP290 is thought to be involved in chromosome segregation and localizes to cilia, centrosomes, and the nucleus. Subsequent analysis of another consanguineous multiplex family revealed homozygous haplotypes and the same frameshift mutation. Our findings add to the increasing body of evidence that ciliopathies can cause a broad spectrum of disease phenotypes, and pleiotropic effects of CEP290 mutations range from single organ involvement with isolated Leber congenital amaurosis to Joubert syndrome and lethal early embryonic multisystemic malformations in Meckel-Gruber syndrome. We compiled clinical and genetic data of all patients with CEP290 mutations described so far. No clear-cut genotype-phenotype correlations were apparent as almost all mutations are nonsense, frameshift, or splice-site changes and scattered throughout the gene irrespective of the patients' phenotypes. Conclusively, other factors than the type and location of CEP290 mutations may underlie phenotypic variability. (c) 2007 Wiley-Liss, Inc.

  8. Identification of host cellular proteins that interact with the M protein of a highly pathogenic porcine reproductive and respiratory syndrome virus vaccine strain.

    Science.gov (United States)

    Wang, Qian; Li, Yanwei; Dong, Hong; Wang, Li; Peng, Jinmei; An, Tongqing; Yang, Xufu; Tian, Zhijun; Cai, Xuehui

    2017-02-22

    The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) continues to pose one of the greatest threats to the swine industry. M protein is the most conserved and important structural protein of PRRSV. However, information about the host cellular proteins that interact with M protein remains limited. Host cellular proteins that interact with the M protein of HP-PRRSV were immunoprecipitated from MARC-145 cells infected with PRRSV HuN4-F112 using the M monoclonal antibody (mAb). The differentially expressed proteins were identified by LC-MS/MS. The screened proteins were used for bioinformatics analysis including Gene Ontology, the interaction network, and the enriched KEGG pathways. Some interested cellular proteins were validated to interact with M protein by CO-IP. The PRRSV HuN4-F112 infection group had 10 bands compared with the control group. The bands included 219 non-redundant cellular proteins that interact with M protein, which were identified by LC-MS/MS with high confidence. The gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway bioinformatic analyses indicated that the identified proteins could be assigned to several different subcellular locations and functional classes. Functional analysis of the interactome profile highlighted cellular pathways associated with protein translation, infectious disease, and signal transduction. Two interested cellular proteins-nuclear factor of activated T cells 45 kDa (NF45) and proliferating cell nuclear antigen (PCNA)-that could interact with M protein were validated by Co-IP and confocal analyses. The interactome data between PRRSV M protein and cellular proteins were identified and contribute to the understanding of the roles of M protein in the replication and pathogenesis of PRRSV. The interactome of M protein will aid studies of virus/host interactions and provide means to decrease the threat of PRRSV to the swine industry in the future.

  9. Is Bloom's Taxonomy Appropriate for Computer Science?

    OpenAIRE

    Johnson, Colin G.; Fuller, Ursula

    2007-01-01

    Bloom's taxonomy attempts to provide a set of levels of cognitive engagement with material being learned. It is usually presented as a generic framework. In this paper we outline some studies which examine whether the taxonomy is appropriate for computing, and how its application in computing might differ from its application elsewhere. We place this in the context of ongoing debates concerning graduateness and attempts to benchmark the content of a computing degree.

  10. Plasma bactericidal/permeability-increasing protein concentrations in critically ill children with the sepsis syndrome.

    Science.gov (United States)

    Wong, H R; Doughty, L A; Wedel, N; White, M; Nelson, B J; Havrilla, N; Carcillo, J A

    1995-12-01

    Bactericidal/permeability-increasing protein (BPI) is a neutrophil azurophilic granule component that is bactericidal towards Gram-negative bacteria and inhibits lipopolysaccharide-mediated inflammatory responses. We conducted a prospective study to measure plasma BPI concentrations in 36 critically ill children with and without the sepsis syndrome. Plasma BPI concentrations ranged from 0.5 to 452 ng/ml. Patients with the sepsis syndrome had higher median plasma BPI concentrations than critically ill controls (5.1 vs. 1.8 ng/ml, P = 0.006). Patients with organ system failure had higher median plasma BPI concentrations than those with no organ system failure (4.5 vs. 1.3 ng/ml, P = 0.001). Plasma BPI concentrations were positively associated with pediatric risk of mortality score (P = 0.03, rs = 0.4). These data provide the first clinical insights regarding the role of endogenous BPI production in critically ill children and suggest that BPI may play an important role in host defenses.

  11. C-reactive protein as a risk factor for acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    杨胜利; 何秉贤; 何作云; 张华; 何学兰; 张伟

    2002-01-01

    Objective We assessed thelevels of C-reactive protein ( CRP ) in patients with acute coronary syndrome (ACS) [including unstable angina pectoris (UAP), acute myocardial infarction (AMI) and sudden cardiac death (SCD) ] compared with non-ACS [including stable angina pectoris (SAP), old myocardial infarction (OMI) and healthy volunteers] and sought to test whether CRP are associated with clinical acute coronary syndrome. Methods Ultrasensitive immunoassay (rate nephelometry with the Beckman Array multitest immunoassay system) wasused to measure CRP levels in 91 patients with ACS(20 UAP, 71 AMI including 2 SCD) and non-ACS (34SAP, 25 patients with healing phase of AMI, 41 OMI and 94 control healthy subjects) Results CRP levels were higher in ACS group (18.50 + 23.98 mg/L [ SE 2.51, n = 91 ] ) compared with non - ACS group (3.89+7.14mg/L[SE0.51, n=194]) (P <0.01).Using Logistic Regression, CRP was a potent determinant of ACS ( OR = 1.65) Conclusion These results suggest that CRP has a strong association with ACS, and CRP is a risk factor of ACS.

  12. Evaluation of salivary gland protein 1 antibodies in patients with primary and secondary Sjogren's syndrome.

    Science.gov (United States)

    Shen, Long; Kapsogeorgou, Efstathia K; Yu, Meixing; Suresh, Lakshmanan; Malyavantham, Kishore; Tzioufas, Anthanasios G; Ambrus, Julian L

    2014-11-01

    Sjogren's syndrome (SS) has been associated with the expression of anti-Ro and anti-La antibodies. Anti-salivary gland protein 1 (SP1) antibodies have recently been identified in patients with SS. The current work involved a cross sectional study to determine whether anti-SP1 antibodies were identified in particular subgroups of patients with SS. The results of this study revealed that anti-SP1 antibodies were present in the sera of 52% of SS patients while anti-Ro/anti-La was present in 63% of patients. 19% of patients had anti-SP1 without anti-Ro/anti-La. Patients with SS and lymphoma expressed anti-Ro, anti-La and anti-SP1 together. In SS associated with RA, 50% had antibodies anti-SP1 while 40% had anti-Ro/anti-La. In conclusion, anti-SP1 antibodies are commonly seen in both primary and secondary SS and rarely in normal controls. Future studies are needed to determine the roles and timing of expression of anti-SP1 antibodies in Sjogren's syndrome.

  13. Cockayne syndrome protein A is a transcription factor of RNA polymerase I and stimulates ribosomal biogenesis and growth

    Science.gov (United States)

    Koch, Sylvia; Garcia Gonzalez, Omar; Assfalg, Robin; Schelling, Adrian; Schäfer, Patrick; Scharffetter-Kochanek, Karin; Iben, Sebastian

    2014-01-01

    Mutations in the Cockayne syndrome A (CSA) protein account for 20% of Cockayne syndrome (CS) cases, a childhood disorder of premature aging and early death. Hitherto, CSA has exclusively been described as DNA repair factor of the transcription-coupled branch of nucleotide excision repair. Here we show a novel function of CSA as transcription factor of RNA polymerase I in the nucleolus. Knockdown of CSA reduces pre-rRNA synthesis by RNA polymerase I. CSA associates with RNA polymerase I and the active fraction of the rDNA and stimulates re-initiation of rDNA transcription by recruiting the Cockayne syndrome proteins TFIIH and CSB. Moreover, compared with CSA deficient parental CS cells, CSA transfected CS cells reveal significantly more rRNA with induced growth and enhanced global translation. A previously unknown global dysregulation of ribosomal biogenesis most likely contributes to the reduced growth and premature aging of CS patients. PMID:24781187

  14. CYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome

    Directory of Open Access Journals (Sweden)

    Barbara eBardoni

    2014-03-01

    Full Text Available Intellectual disability (ID and autism spectrum disorders (ADS have in common alterations in some brain circuits and brain abnormalities, such as synaptic transmission and dendritic spines morphology. Recent studies have indicated a differential expression for specific categories of genes as a cause for both types of disease, while an increasing number of genes is recognized to produce both disorders. An example is the Fragile X Mental retardation gene, FMR1, whose silencing causes the Fragile X syndrome, the most common form of intellectual disability and autism, also characterized by physical hallmarks. FMRP, the protein encoded by FMR1, is an RNA-binding protein with an important role in translational control. Among the interactors of FMRP, CYFIP1/2 proteins are good candidates for intellectual disability and autism, on the bases of their genetic implication and functional properties, even if the precise functional significance of the CYFIP/FMRP interaction is not understood yet. CYFIP1 and CYFIP2 represent a link between Rac1, the Wave complex and FMRP, favoring the cross talk between actin polymerization and translational control

  15. Localization studies of two white spot syndrome virus structural proteins VP51 and VP76

    Directory of Open Access Journals (Sweden)

    Yang Feng

    2006-09-01

    Full Text Available Abstract VP51 and VP76 are two structural proteins of white spot syndrome virus (WSSV. However, there is some controversy about their localization in the virion at present. In this study, we employ multiple approaches to reevaluate the location of VP51 and VP76. Firstly, we found VP51 and VP76 presence in viral nucleocapsids fraction by Western blotting. Secondly, after the high-salt treatment of nucleocapsids, VP51 and VP76 were still exclusively present in viral capsids by Western blotting and immunoelectron microscopy, suggesting two proteins are structural components of the viral capsid. To gather more evidence, we developed a method based on immunofluorescence flow cytometry. The results revealed that the mean fluorescence intensity of the viral capsids group was significantly higher than that of intact virions group after incubation with anti-VP51 or anti-VP76 serum and fluorescein isothiocyanate conjugated secondary antibody. All these results indicate that VP51 and VP76 are both capsid proteins of WSSV.

  16. The effect of milk and milk proteins on risk factors of metabolic syndrome in overweight adolecents

    DEFF Research Database (Denmark)

    Arnberg, Karina

    of type-2 diabetes and atherosclerotic cardiovascular diseases. Overweight children have higher concentrations of the metabolic syndrome risk factors than normal weight children and the pathological condition underlying cardiovascular diseases, called atherosclerosis, seems to start in childhood. A well...... in the adolescents. The analyses showed that increased physical activity was related to an improved arterial function whereas central adiposity and a high protein intake were related to increased arterial stiffness. In the intervention study, the adolescents with habitual low milk intakes were randomized to drink 1L...... factors than children having a high milk intake. The aim of the intervention study was to examine whether it is beneficial for overweight adolescents with a habitual low milk intake to increase the consumption of low fat milk and whether a potential beneficial effect is caused by whey or casein. The data...

  17. Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates.

    Science.gov (United States)

    Ross, Alison J; May-Simera, Helen; Eichers, Erica R; Kai, Masatake; Hill, Josephine; Jagger, Daniel J; Leitch, Carmen C; Chapple, J Paul; Munro, Peter M; Fisher, Shannon; Tan, Perciliz L; Phillips, Helen M; Leroux, Michel R; Henderson, Deborah J; Murdoch, Jennifer N; Copp, Andrew J; Eliot, Marie-Madeleine; Lupski, James R; Kemp, David T; Dollfus, Hélène; Tada, Masazumi; Katsanis, Nicholas; Forge, Andrew; Beales, Philip L

    2005-10-01

    The evolutionarily conserved planar cell polarity (PCP) pathway (or noncanonical Wnt pathway) drives several important cellular processes, including epithelial cell polarization, cell migration and mitotic spindle orientation. In vertebrates, PCP genes have a vital role in polarized convergent extension movements during gastrulation and neurulation. Here we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction, share phenotypes with PCP mutants including open eyelids, neural tube defects and disrupted cochlear stereociliary bundles. Furthermore, we identify genetic interactions between BBS genes and a PCP gene in both mouse (Ltap, also called Vangl2) and zebrafish (vangl2). In zebrafish, the augmented phenotype results from enhanced defective convergent extension movements. We also show that Vangl2 localizes to the basal body and axoneme of ciliated cells, a pattern reminiscent of that of the BBS proteins. These data suggest that cilia are intrinsically involved in PCP processes.

  18. [Cloning and sequence analysis of 55 K protein of egg drop syndrome virus].

    Science.gov (United States)

    Zhu, L; Jin, Q; Zeng, L

    1999-06-30

    For understanding the characteristics of genomic structure of egg drop syndrome virus(EDSV). Nucleic acid was extracted using routine method from weak virulent strain AA-2 of EDSV isolated from Chinese sick hens. Construction of the whole genomic library was by hydrolysis with Hind III, strand encoding 55 K gene locating in Hind III--A segment was sequenced and analyzed. The open reading frame has a length of 1,014 nt and codes a polypeptide of 337 amino acids with molecular weight of 38,200. Analysis of the amino acid sequence revealed a homology from 25.5%-32.4% to the 55 K protein of human adenovirus types 2, 12, 40, canine adenovirus and fowl adenoviruses of group 1, whereas to ovine adenovirus is 46.4%. The genomic structure of EDSV has some relationship with adenoviruses.

  19. C-reactive protein in the periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome.

    Science.gov (United States)

    Førsvoll, Jostein A; Oymar, Knut

    2007-11-01

    To evaluate levels of C-reactive protein (CRP) during febrile episodes in children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA). All CRP values during typical episodes of fever in children diagnosed with PFAPA during a 3 years period were retrospectively registered. In 16 children with PFAPA, a total of 87 CRP values were registered during 38 episodes of fever. The mean of the maximum CRP during each episode was 185 mg/L (SD: 69.4, range: 45-322). Values of CRP were elevated throughout the whole period of fever, with higher values on days 2-4 compared to day 1. Levels of CRP are substantially increased during febrile episodes in children with PFAPA. High levels of CRP may suggest a role for immunological mechanisms in PFAPA, and may raise the suspicion of PFAPA when measured in children with periodic fever of unknown origin.

  20. Protein-energy malnutrition is frequent and precocious in children with cri du chat syndrome.

    Science.gov (United States)

    Lefranc, Violaine; de Luca, Arnaud; Hankard, Régis

    2016-05-01

    Protein-energy malnutrition (PEM) is poorly reported in cri du chat syndrome (CDCS) (OMIM #123450), a genetic disease that causes developmental delay and global growth retardation. The objective was to determine the nutritional status at different ages in children with CDCS and factors associated with PEM. A questionnaire focused on growth and nutritional care was sent to 190 families. Among 36 analyzable questionnaires, growth and nutritional indices compatible with PEM occurred in 47% of patients: 19% before 6 months of age, 24% between 6-12 months and 34% after 12 months. Eight patients received enteral feeding. Speech therapy for swallowing education was performed more often in malnourished children (63% vs. 22%, P < 0.02). PEM is frequent and occurs early in this disease, requiring closed nutritional monitoring.

  1. Wiskott-Aldrich Syndrome Protein Regulates Leukocyte-Dependent Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Dan Ishihara

    2013-08-01

    Full Text Available A paracrine interaction between epidermal growth factor (EGF-secreting tumor-associated macrophages (TAMs and colony-stimulating factor 1 (CSF-1-secreting breast carcinoma cells promotes invasion and metastasis. Here, we show that mice deficient in the hematopoietic-cell-specific Wiskott-Aldrich syndrome protein (WASp are unable to support TAM-dependent carcinoma cell invasion and metastasis in both orthotopic and transgenic models of mammary tumorigenesis. Motility and invasion defects of tumor cells were recapitulated ex vivo upon coculture with WASp−/− macrophages. Mechanistically, WASp is required for macrophages to migrate toward CSF-1-producing carcinoma cells, as well as for the release of EGF through metalloprotease-dependent shedding of EGF from the cell surface of macrophages. Our findings suggest that WASp acts to support both the migration of TAMs and the production of EGF, which in concert promote breast tumor metastasis.

  2. Changes of pregnancy-associated plasma protein-A in patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    LIU Jin-lai; ZHANG Hui; XIE Xu-jing; CHEN Lin; ZHAO Chang-lin

    2005-01-01

    @@ The term vulnerable patient has been proposed to define subjects susceptible to an acute coronary syndrome (ACS) or sudden cardiac death based on plaque characteristics, blood abnorma-lities, or myocardial vulnerability.1 It will be important in the future to identify both vulnerable patients and vulnerable plaques. Atherosclerotic arteries obtained at autopsy from patients who died suddenly of cardiac causes indicate that pregnancy-associated plasma protein-A (PAPP-A) was abundantly expressed in plaque cells and in the extracellular matrix of ruptured and eroded unstable plaques, but not in stable plaques.2 Here we examined circulating PAPP-A levels in patients with ACS in order to evaluate its potential use in identifying vulnerable patients.

  3. CASP3 protein expression by flow cytometry in Down's syndrome subjects.

    Science.gov (United States)

    Salemi, Michele; Condorelli, Rosita A; Romano, Corrado; Concetta, Barone; Romano, Carmelo; Salluzzo, Maria Grazia; Bosco, Paolo; Calogero, Aldo E

    2014-01-01

    Down's syndrome (DS), the most common chromosomal disorder, is caused by 21 trisomy and is featured by intellectual disability. Subjects with DS can develop some traits of Alzheimer disease (AD) at an earlier age than subjects without trisomy 21. Apoptosis is a programmed cell death process under both normal physiological and pathological conditions. Caspase-3 (CASP3) plays an important role in neuronal death during nervous system development and under certain pathological conditions. Furthermore, in vitro and in vivo studies report elevated expression and activation of CASP3 in models of AD. On this account, the expression of CASP3 gene was evaluated in cultures of fibroblasts of DS and normal subjects by flow cytometry. CASP3 protein was up-regulated in fibroblasts of DS. The data obtained from this study strengthen the hypothesis that the over-expression of CASP3 gene could have a role in the activation of the apoptotic pathways acting in the neurodegenerative processes in DS.

  4. Increased plasma amyloid beta protein 1-42 levels in Down syndrome.

    Science.gov (United States)

    Mehta, P D; Dalton, A J; Mehta, S P; Kim, K S; Sersen, E A; Wisniewski, H M

    1998-01-23

    Amyloid beta protein 1-40 (A beta40) and A beta42 levels were quantitated in plasma from 43 persons with Down syndrome (DS; 26-68 years of age), 43 age-matched normal controls, and 19 non-DS mentally retarded (MR) persons (26-91 years of age) by using a sandwich enzyme linked immunosorbent assay. A beta40 levels were higher in DS and MR than controls, but were similar between DS and MR groups. A beta42 levels were higher in DS than controls or MR persons. The ratios of A beta42/A beta40 were higher in DS than controls or MR persons. The findings are consistent with those seen in DS brains.

  5. Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase

    DEFF Research Database (Denmark)

    Rosenthal, Andrew S; Dexheimer, Thomas S; Gileadi, Opher;

    2013-01-01

    complementary strands of duplex DNA as well as atypical DNA structures such as Holliday junctions. Mutations of the BLM gene can result in Bloom syndrome, an autosomal recessive disorder associated with cancer predisposition. BLM-deficient cells exhibit increased sensitivity to DNA damaging agents indicating...... and related analogs, which possess potent BLM inhibition and exhibit selectivity over related helicases. Moreover, these compounds demonstrated cellular activity by inducing sister chromatid exchanges, a hallmark of Bloom syndrome.......Human cells utilize a variety of complex DNA repair mechanisms in order to combat constant mutagenic and cytotoxic threats from both exogenous and endogenous sources. The RecQ family of DNA helicases, which includes Bloom helicase (BLM), plays an important function in DNA repair by unwinding...

  6. Cockayne syndrome group B protein promotes mitochondrial DNA stability by supporting the DNA repair association with the mitochondrial membrane

    DEFF Research Database (Denmark)

    Aamann, Maria Diget; Sorensen, Martin M; Hvitby, Christina Poulsen;

    2010-01-01

    Cockayne syndrome (CS) is a human premature aging disorder associated with severe developmental deficiencies and neurodegeneration, and phenotypically it resembles some mitochondrial DNA (mtDNA) diseases. Most patients belong to complementation group B, and the CS group B (CSB) protein plays a role...

  7. Middle east respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus ankara efficiently induces virus-neutralizing antibodies

    NARCIS (Netherlands)

    F. Song (Fei); R. Fux (Robert); L.B.V. Provacia (Lisette); A. Volz (Asisa); M. Eickmann; S. Becker (Stephan); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart); G. Suttera (Gerd)

    2013-01-01

    textabstractMiddle East respiratory syndrome coronavirus (MERS-CoV) has recently emerged as a causative agent of severe respiratory disease in humans. Here, we constructed recombinant modified vaccinia virus Ankara (MVA) expressing full-length MERS-CoV spike (S) protein (MVA-MERS-S). The genetic sta

  8. Protein profiling in the gut of Penaeus monodon gavaged with oral WSSV-vaccines and live white spot syndrom virus

    NARCIS (Netherlands)

    Kulkarni, A.D.; Kiron, V.; Rombout, J.H.W.M.; Brinchmann, M.; Fernandes, J.M.O.; Sudheer, N.S.; Singh, B.I.S.

    2014-01-01

    White spot syndrome virus (WSSV) is a pathogen that causes considerable mortality of the farmed shrimp, Penaeus monodon. Candidate ‘vaccines’, WSSV envelope protein VP28 and formalin-inactivated WSSV, can provide short-lived protection against the virus. In this study, P. monodon was orally intubate

  9. Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

    NARCIS (Netherlands)

    Stiff, T.; Alagoz, M.; Alcantara, D.; Outwin, E.; Brunner, H.G.; Bongers, M.H.F.; O'Driscoll, M.; Jeggo, P.A.

    2013-01-01

    Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions duri

  10. Epigenetic regulation in amyloid precursor protein and the Lesch-Nyhan syndrome.

    Science.gov (United States)

    Nguyen, Khue Vu

    2014-04-18

    Lesch-Nyhan syndrome (LNS) is a neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HPRT) is defective. A major unsolved question is how the loss of HPRT enzyme function affects the brain to cause the neurobehavioural syndrome in LNS and its attenuated variants (LNVs). To address this issue, a search for a link between LNS and the amyloid precursor protein (APP) is developed. Here, I identified, for the first time in fibroblasts from normal subjects as well as from LNS and LNV patients: (a) several APP-mRNA isoforms encoding divers APP protein isoforms ranging from 120 to 770 amino acids (with or without mutations and/or deletions) accounted for epigenetic mechanisms in the regulation of alternative APP pre-mRNA splicing and (b) five novel independent polymorphisms in the APP promoter: -956A>G, -1023T>C, -1161A>G, -2224G>A, -2335C>T relative to the transcription start site. A role for epistasis between mutated HPRT and APP genes affecting the regulation of alternative APP pre-mRNA splicing in LNS is suggested. An accurate quantification of various APP isoforms in brain tissues for detection of initial pathological changes or pathology development is needed. My findings may provide new directions not only for investigating the role of APP in neuropathology associated with HPRT-deficiency in LNS but also for the research in neurodevelopmental and neurodegenerative disorders by which various APP isoforms involved in the pathogenesis of the diseases such as Alzheimer's disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Sucrose in bloom-forming cyanobacteria: loss and gain of genes involved in its biosynthesis.

    Science.gov (United States)

    Kolman, María A; Salerno, Graciela L

    2016-02-01

    Bloom-forming cyanobacteria are widely distributed in freshwater ecosystems. To cope with salinity fluctuations, cyanobacteria synthesize compatible solutes, such as sucrose, to maintain the intracellular osmotic balance. The screening of cyanobacterial genomes revealed that homologues to sucrose metabolism-related genes only occur in few bloom-forming strains, mostly belonging to Nostocales and Stigonematales orders. Remarkably, among Chroococcales and Oscillatoriales strains, homologues were only found in M. aeruginosa PCC 7806 and Leptolyngbya boryana PCC 6306, suggesting a massive loss of sucrose metabolism in bloom-forming strains of these orders. After a complete functional characterization of sucrose genes in M. aeruginosa PCC 7806, we showed that sucrose metabolism depends on the expression of a gene cluster that defines a transcriptional unit, unique among all sucrose-containing cyanobacteria. It was also demonstrated that the expression of the encoding genes of sucrose-related proteins is stimulated by salt. In view of its ancestral origin in cyanobacteria, the fact that most bloom-forming strains lack sucrose metabolism indicates that the genes involved might have been lost during evolution. However, in a particular strain, like M. aeruginosa PCC 7806, sucrose synthesis genes were probably regained by horizontal gene transfer, which could be hypothesized as a response to salinity fluctuations.

  12. Meckel-Gruber syndrome protein MKS3 is required for endoplasmic reticulum-associated degradation of surfactant protein C.

    Science.gov (United States)

    Wang, Mei; Bridges, James P; Na, Cheng-Lun; Xu, Yan; Weaver, Timothy E

    2009-11-27

    Autosomal dominant mutations in the SFTPC gene are associated with idiopathic pulmonary fibrosis, a progressive lethal interstitial lung disease. Mutations that cause misfolding of the encoded proprotein surfactant protein C (SP-C) trigger endoplasmic reticulum (ER)-associated degradation, a pathway that segregates terminally misfolded substrate for retrotranslocation to the cytosol and degradation by proteasome. Microarray screens for genes involved in SP-C ER-associated degradation identified MKS3/TMEM67, a locus previously linked to the ciliopathy Meckel-Gruber syndrome. In this study, MKS3 was identified as a membrane glycoprotein predominantly localized to the ER. Expression of MKS3 was up-regulated by genetic or pharmacological inducers of ER stress. The ER lumenal domain of MKS3 interacted with a complex that included mutant SP-C and associated chaperones, whereas the region predicted to encode the transmembrane domains of MKS3 interacted with cytosolic p97. Deletion of the transmembrane and cytosolic domains abrogated interaction of MKS3 with p97 and resulted in accumulation of mutant SP-C proprotein; knockdown of MKS3 also inhibited degradation of mutant SP-C. These results support a model in which MKS3 links the ER lumenal quality control machinery with the cytosolic degradation apparatus.

  13. Meckel-Gruber Syndrome Protein MKS3 Is Required for Endoplasmic Reticulum-associated Degradation of Surfactant Protein C*

    Science.gov (United States)

    Wang, Mei; Bridges, James P.; Na, Cheng-Lun; Xu, Yan; Weaver, Timothy E.

    2009-01-01

    Autosomal dominant mutations in the SFTPC gene are associated with idiopathic pulmonary fibrosis, a progressive lethal interstitial lung disease. Mutations that cause misfolding of the encoded proprotein surfactant protein C (SP-C) trigger endoplasmic reticulum (ER)-associated degradation, a pathway that segregates terminally misfolded substrate for retrotranslocation to the cytosol and degradation by proteasome. Microarray screens for genes involved in SP-C ER-associated degradation identified MKS3/TMEM67, a locus previously linked to the ciliopathy Meckel-Gruber syndrome. In this study, MKS3 was identified as a membrane glycoprotein predominantly localized to the ER. Expression of MKS3 was up-regulated by genetic or pharmacological inducers of ER stress. The ER lumenal domain of MKS3 interacted with a complex that included mutant SP-C and associated chaperones, whereas the region predicted to encode the transmembrane domains of MKS3 interacted with cytosolic p97. Deletion of the transmembrane and cytosolic domains abrogated interaction of MKS3 with p97 and resulted in accumulation of mutant SP-C proprotein; knockdown of MKS3 also inhibited degradation of mutant SP-C. These results support a model in which MKS3 links the ER lumenal quality control machinery with the cytosolic degradation apparatus. PMID:19815549

  14. Colonic expression of Runx3 protein and TGF-β1 and their correlation in patients with irritable bowel syndrome

    Institute of Scientific and Technical Information of China (English)

    Xiaoning Sun; Cheng Lan; Yu An; Ye Sun

    2011-01-01

    Objective:To investigate the role of Runx3 protein and TGF-β1 in the pathogenesis of irritable bowel syndrome(IBS), as well as the correlation of these two proteins.Methods: Colonic tissue was collected from patients with IBS and normal persons. The colonic expression of Runx3 protein andTGF-β1 was detected with immunohistochemistry method. Semi-quantitative analysis was used to evaluate the staining degree of these two proteins.Results: Compared with their counterparts, patients withIBS did not show any changes in the colonic expression of Runx3 protein andTGF-β1 (P>0.05). Interestingly, there was a significant correlation between Runx3 protein andTGF-β1 in patients withIBS(P<0.05).Conclusions:The role of Runx3 protein and TGF-β1 in the pathogenesis ofIBS remains to be further studied.

  15. A PTPN11 allele encoding a catalytically impaired SHP2 protein in a patient with a Noonan syndrome phenotype.

    Science.gov (United States)

    Edwards, Jonathan J; Martinelli, Simone; Pannone, Luca; Lo, Ivan Fai-Man; Shi, Lisong; Edelmann, Lisa; Tartaglia, Marco; Luk, Ho-Ming; Gelb, Bruce D

    2014-09-01

    The RASopathies are a relatively common group of phenotypically similar and genetically related autosomal dominant genetic syndromes caused by missense mutations affecting genes participating in the RAS/mitogen-activated protein kinase (MAPK) pathway that include Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML, formerly LEOPARD syndrome). NS and NSML can be difficult to differentiate during infancy, but the presence of multiple lentigines, café au lait spots, and specific cardiac defects facilitate the diagnosis. Furthermore, individual PTPN11 missense mutations are highly specific to each syndrome and engender opposite biochemical alterations on the function of SHP-2, the protein product of that gene. Here, we report on a 5-year-old male with two de novo PTPN11 mutations in cis, c.1471C>T (p.Pro491Ser), and c.1492C>T (p.Arg498Trp), which are associated with NS and NSML, respectively. This boy's phenotype is intermediate between NS and NSML with facial dysmorphism, short stature, mild global developmental delay, pulmonic stenosis, and deafness but absence of café au lait spots or lentigines. The double-mutant SHP-2 was found to be catalytically impaired. This raises the question of whether clinical differences between NS and NSML can be ascribed solely to the relative SHP-2 catalytic activity.

  16. Phytoplankton-Associated Bacterial Community Composition and Succession during Toxic Diatom Bloom and Non-Bloom Events

    Science.gov (United States)

    Sison-Mangus, Marilou P.; Jiang, Sunny; Kudela, Raphael M.; Mehic, Sanjin

    2016-01-01

    Pseudo-nitzschia blooms often occur in coastal and open ocean environments, sometimes leading to the production of the neurotoxin domoic acid that can cause severe negative impacts to higher trophic levels. Increasing evidence suggests a close relationship between phytoplankton bloom and bacterial assemblages, however, the microbial composition and succession during a bloom process is unknown. Here, we investigate the bacterial assemblages before, during and after toxic and non-toxic Pseudo-nitzschia blooms to determine the patterns of bacterial succession in a natural bloom setting. Opportunistic sampling of bacterial community profiles were determined weekly at Santa Cruz Municipal Wharf by 454 pyrosequencing and analyzed together with domoic acid levels, phytoplankton community and biomass, nutrients and temperature. We asked if the bacterial communities are similar between bloom and non-bloom events and if domoic acid or the presence of toxic algal species acts as a driving force that can significantly structure phytoplankton-associated bacterial communities. We found that bacterial diversity generally increases when Pseudo-nitzschia numbers decline. Furthermore, bacterial diversity is higher when the low-DA producing P. fraudulenta dominates the algal bloom while bacterial diversity is lower when high-DA producing P. australis dominates the algal bloom, suggesting that the presence of algal toxin can structure bacterial community. We also found bloom-related succession patterns among associated bacterial groups; Gamma-proteobacteria, were dominant during low toxic P. fraudulenta blooms comprising mostly of Vibrio spp., which increased in relative abundance (6–65%) as the bloom progresses. On the other hand, Firmicutes bacteria comprising mostly of Planococcus spp. (12–86%) dominate during high toxic P. australis blooms, with the bacterial assemblage showing the same bloom-related successional patterns in three independent bloom events. Other environmental

  17. Changes in adenosine 5'-monophosphate-activated protein kinase as a mechanism of visceral obesity in Cushing's syndrome.

    Science.gov (United States)

    Kola, Blerina; Christ-Crain, Mirjam; Lolli, Francesca; Arnaldi, Giorgio; Giacchetti, Gilberta; Boscaro, Marco; Grossman, Ashley B; Korbonits, Márta

    2008-12-01

    Features of the metabolic syndrome such as central obesity with insulin resistance and dyslipidemia are typical signs of Cushing's syndrome and common side effects of prolonged glucocorticoid treatment. AMP-activated protein kinase (AMPK), a key regulatory enzyme of lipid and carbohydrate metabolism as well as appetite, is involved in the development of the deleterious metabolic effects of excess glucocorticoids, but no data are available in humans. In the current study, we demonstrate the effect of high glucocorticoid levels on AMPK activity of human adipose tissue samples from patients with Cushing's syndrome. AMPK activity and mRNA expression of genes involved in lipid metabolism were assessed in visceral adipose tissue removed at abdominal surgery of 11 patients with Cushing's syndrome, nine sex-, age-, and weight-matched patients with adrenal incidentalomas, and in visceral adipose tissue from four patients with non-endocrine-related abdominal surgery. The patients with Cushing's syndrome exhibited a 70% lower AMPK activity in visceral adipose tissue as compared with both incidentalomas and control patients (P = 0.007 and P cortisol and with urinary free cortisol. Our data suggest that glucocorticoids inhibit AMPK activity in adipose tissue, suggesting a novel mechanism to explain the deposition of visceral adipose tissue and the consequent central obesity observed in patients with iatrogenic or endogenous Cushing's syndrome.

  18. Atomic force microscopy-based antibody recognition imaging of proteins in the pathological deposits in Pseudoexfoliation Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Creasey, Rhiannon [School of Chemical and Physical Sciences, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Sharma, Shiwani [School of Medicine, Ophthalmology, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Gibson, Christopher T. [School of Chemical and Physical Sciences, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Craig, Jamie E. [School of Medicine, Ophthalmology, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia); Ebner, Andreas [Institute for Biophysics, Johannes Kepler Universitaet Linz, Altenbergerstr. 69, A-4040 Linz (Austria); Becker, Thomas [Nanochemistry Research Institute, Curtin University, GPO Box U1987, Perth, 6845 WA (Australia); Hinterdorfer, Peter [Institute for Biophysics, Johannes Kepler Universitaet Linz, Altenbergerstr. 69, A-4040 Linz (Austria); Voelcker, Nicolas H., E-mail: nico.voelcker@flinders.edu.au [School of Chemical and Physical Sciences, Flinders University of SA, GPO Box 2100, Adelaide, SA 5001 (Australia)

    2011-07-15

    The phenomenon of protein aggregation is of considerable interest to various disciplines, including the field of medicine. A range of disease pathologies are associated with this phenomenon. One of the ocular diseases hallmarked by protein aggregation is the Pseudoexfoliation (PEX) Syndrome. This condition is characterized by the deposition of insoluble proteinaceous material on the anterior human lens capsule. Genomic and proteomic analyses have revealed an association of specific genetic markers and various proteins, respectively, with PEX syndrome. However, the ultrastructure of the protein aggregates is poorly characterized. This study seeks to build capacity to determine the molecular nature of PEX aggregates on human lens capsules in their native state by AFM-based antibody recognition imaging. Lysyl oxidase-Like 1 (LOXL1), a protein identified as a component of PEX aggregates, is detected by an antibody-modified AFM probe. Topographical AFM images and antibody recognition images are obtained using three AFM-based techniques: TREC, phase and force-volume imaging. LOXL1 is found to be present on the lens capsule surface, and is localized around fibrous protein aggregates. Our evaluation shows that TREC imaging is best suited for human tissue imaging and holds significant potential for imaging of human disease tissues in their native state. -- Highlights: {yields} Atomic force microscopy techniques were applied to diseased human tissues. {yields} LOXL1 protein was detected on the small fibers of Pseudoexfoliation deposits. {yields} PicoTREC was the optimum technique for investigating protein aggregates.

  19. Characterization of a dominant negative C. elegans Twist mutant protein with implications for human Saethre-Chotzen syndrome.

    Science.gov (United States)

    Corsi, Ann K; Brodigan, Thomas M; Jorgensen, Erik M; Krause, Michael

    2002-06-01

    Twist is a transcription factor that is required for mesodermal cell fates in all animals studied to date. Mutations of this locus in humans have been identified as the cause of the craniofacial disorder Saethre-Chotzen syndrome. The Caenorhabditis elegans Twist homolog is required for the development of a subset of the mesoderm. A semidominant allele of the gene that codes for CeTwist, hlh-8, has defects that occur earlier in the mesodermal lineage than a previously studied null allele of the gene. The semidominant allele has a charge change (E29K) in the basic DNA-binding domain of CeTwist. Surprisingly, the mutant protein retains DNA-binding activity as both a homodimer and a heterodimer with its partner E/Daughterless (CeE/DA). However, the mutant protein blocks the activation of the promoter of a target gene. Therefore, the mutant CeTwist may cause cellular defects as a dominant negative protein by binding to target promoters as a homo- or heterodimer and then blocking transcription. Similar phenotypes as those caused by the E29K mutation were observed when amino acid substitutions in the DNA-binding domain that are associated with the human Saethre-Chotzen syndrome were engineered into the C. elegans protein. These data suggest that Saethre-Chotzen syndrome may be caused, in some cases, by dominant negative proteins, rather than by haploinsufficiency of the locus.

  20. A calcineurin inhibitory protein overexpressed in Down's syndrome interacts with the product of a ubiquitously expressed transcript

    Directory of Open Access Journals (Sweden)

    H.C.S. Silveira

    2004-06-01

    Full Text Available The Down's syndrome candidate region 1 (DSCR1 protein, encoded by a gene located in the human chromosome 21, interacts with calcineurin and is overexpressed in Down's syndrome patients. As an approach to clarifying a putative function for this protein, in the present study we used the yeast two-hybrid system to identify DSCR1 partners. The two-hybrid system is a method that allows the identification of protein-protein interactions through reconstitution of the activity of the yeast GAL 4 transcriptional activator. The gene DSCR1 fused to the GAL 4 binding domain (BD was used to screen a human fetal brain cDNA library cloned in fusion with the GAL 4 activation domain (AD. Three positive clones were found and sequence analysis revealed that all the plasmids coded for the ubiquitously expressed transcript (UXT. UXT, which is encoded in human Xp11, is a 157-amino acid protein present in both cytosol and nucleus of the cells. This positive interaction of DSCR1 and UXT was confirmed in vivo by mating the yeast strain AH109 (MATaexpressing AD-UXT with the strain Y187 (MATalpha expressing BD-DSCR1, and in vitro by co-immunoprecipitation experiments. These results may help elucidate a new function for DSCR1 and its participation in Down's syndrome pathogenesis.

  1. ICP35 Is a TREX-Like Protein Identified in White Spot Syndrome Virus

    Science.gov (United States)

    Phairoh, Panapat; Suthibatpong, Thana; Rattanarojpong, Triwit; Jongruja, Nujarin; Senapin, Saengchan; Choowongkomon, Kiattawee; Khunrae, Pongsak

    2016-01-01

    ICP35 is a non-structural protein from White spot syndrome virus believed to be important in viral replication. Since ICP35 was found to localize in the host nucleus, it has been speculated that the function of ICP35 might be involved in the interaction of DNA. In this study, we overexpressed, purified and characterized ICP35. The thioredoxin-fused ICP35 (thio-ICP35) was strongly expressed in E. coli and be able to form itself into dimers. Investigation of the interaction between ICP35 and DNA revealed that ICP35 can perform DNase activity. Structural model of ICP35 was successfully built on TREX1, suggesting that ICP35 might adopt the folding similar to that of TREX1 protein. Several residues important for dimerization in TREX1 are also conserved in ICP35. Residue Asn126 and Asp132, which are seen to be in close proximity to metal ions in the ICP35 model, were shown through site-directed mutagenesis to be critical for DNase activity. PMID:27348862

  2. Tricornered Kinase Regulates Synapse Development by Regulating the Levels of Wiskott-Aldrich Syndrome Protein.

    Directory of Open Access Journals (Sweden)

    Rajalaxmi Natarajan

    Full Text Available Precise regulation of synapses during development is essential to ensure accurate neural connectivity and function of nervous system. Many signaling pathways, including the mTOR (mechanical Target of Rapamycin pathway operate in neurons to maintain genetically determined number of synapses during development. mTOR, a kinase, is shared between two functionally distinct multi-protein complexes- mTORC1 and mTORC2, that act downstream of Tuberous Sclerosis Complex (TSC. We and others have suggested an important role for TSC in synapse development at the Drosophila neuromuscular junction (NMJ synapses. In addition, our data suggested that the regulation of the NMJ synapse numbers in Drosophila largely depends on signaling via mTORC2. In the present study, we further this observation by identifying Tricornered (Trc kinase, a serine/threonine kinase as a likely mediator of TSC signaling. trc genetically interacts with Tsc2 to regulate the number of synapses. In addition, Tsc2 and trc mutants exhibit a dramatic reduction in synaptic levels of WASP, an important regulator of actin polymerization. We show that Trc regulates the WASP levels largely, by regulating the transcription of WASP. Finally, we show that overexpression of WASP (Wiskott-Aldrich Syndrome Protein in trc mutants can suppress the increase in the number of synapses observed in trc mutants, suggesting that WASP regulates synapses downstream of Trc. Thus, our data provide a novel insight into how Trc may regulate the genetic program that controls the number of synapses during development.

  3. Hematochezia before the First Feeding in a Newborn with Food Protein-Induced Enterocolitis Syndrome

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    Masanori Mizuno

    2011-09-01

    Full Text Available The prevalence and incidence of food protein-induced enterocolitis syndrome (FPIES are clearly not known; its onset before first feeding at birth especially has been rarely reported. A female newborn was referred to our institution due to blood-stained diarrhea before her first feeding at birth. Examination of the stool with Wright-Giemsa staining on day 6 revealed numerous fecal eosinophils, including Charcot-Leyden crystals. Lymphocyte stimulation test (LST against cow's milk protein also showed positive values on day 12. The hematochezia resolved immediately after starting intravenous nutrition. She was fed with breast milk and extensively hydrolyzed formula and discharged from hospital on day 49. FPIES was diagnosed based on these symptoms and data. Our case was thought to have acquired allergic enterocolitis after sensitization in her fetal period, which caused severe FPIES triggered by the first intake of cow's milk soon after birth. The patient with FPIES presents atypical clinical findings, which is likely to cause misdiagnosis and delay of appropriate treatment. Heightened awareness and increased attention may be necessary to diagnose FPIES, even soon after birth. Evaluating fecal eosinophils and LST, which may be difficult to perform in every clinical hospital, is thought to be useful for the detection of FPIES without oral food challenge.

  4. Eosinophilia in infants with food protein-induced enterocolitis syndrome in Japan.

    Science.gov (United States)

    Kimura, Mitsuaki; Shimomura, Masaki; Morishita, Hideaki; Meguro, Takaaki; Seto, Shiro

    2017-04-01

    Many Japanese infants with food protein-induced enterocolitis syndrome (FPIES) show eosinophilia, which has been thought to be a characteristic of food protein-induced proctocolitis (FPIP). To elucidate the characteristics of eosinophilia in Japanese FPIES patients, 113 infants with non-IgE-mediated gastrointestinal food allergy due to cow's milk were enrolled and classified into FPIES (n = 94) and FPIP (n = 19). The percentage of peripheral blood eosinophils (Eo) was increased in most FPIES patients (median, 7.5%), which was comparable with that in FPIP patients (9.0%). Among FPIES patients, Eo was the highest in patients who had vomiting, bloody stool, and diarrhea simultaneously (12.9%) and lowest in patients with diarrhea alone (3.2%). Eo showed a significant positive correlation with the incidence of vomiting (Cramer's V = 0.31, p 10 days, n = 38) FPIES (median, 9.8% vs. 5.4%; p eosinophilia in Japanese FPIES infants: conspicuous and mild eosinophilia in early- and late-onset FPIES patients, respectively. Conspicuous eosinophilia in early-onset FPIES is suggested to be caused by abnormally high IL-5 production. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  5. Severe Food Protein-Induced Enterocolitis Syndrome to Cow’s Milk in Infants

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    Min Yang

    2015-12-01

    Full Text Available Cow’s milk is the most common cause of food-protein-induced enterocolitis syndrome (FPIES. The aim of this study was to examine the clinical features and treatment outcomes of infants with severe FPIES to cow’s milk. We reviewed all infants ≤12 months of age who were hospitalized and diagnosed with severe FPIES to cow’s milk between 1 January 2011 and 31 August 2014 in a tertiary Children’s Medical Center in China. Patients’ clinical features, feeding patterns, laboratory tests, and treatment outcomes were reviewed. A total of 12 infants met the inclusion criteria. All infants presented with diarrhea, edema, and hypoalbuminemia. Other main clinical manifestations included regurgitation/vomiting, skin rashes, low-grade fever, bloody and/or mucous stools, abdominal distention, and failure to thrive. They had clinical remission with resolution of diarrhea and significant increase of serum albumin after elimination of cow’s milk protein (CMP from the diet. The majority of infants developed tolerance to the CMP challenge test after 12 months of avoidance. In conclusion, we reported the clinical experience of 12 infants with severe FPIES to cow’s milk, which resulted in malnutrition, hypoproteinemia, and failure to thrive. Prompt treatment with CMP-free formula is effective and leads to clinical remission of FPIES in infants.

  6. A Wiskott-Aldrich syndrome protein is involved in endocytosis in Aspergillus nidulans.

    Science.gov (United States)

    Hoshi, Hiro-Omi; Zheng, Lu; Ohta, Akinori; Horiuchi, Hiroyuki

    2016-09-01

    Endocytosis is vital for hyphal tip growth in filamentous fungi and is involved in the tip localization of various membrane proteins. To investigate the function of a Wiskott-Aldrich syndrome protein (WASP) in endocytosis of filamentous fungi, we identified a WASP ortholog-encoding gene, wspA, in Aspergillus nidulans and characterized it. The wspA product, WspA, localized to the tips of germ tubes during germination and actin rings in the subapical regions of mature hyphae. wspA is essential for the growth and functioned in the polarity establishment and maintenance during germination of conidia. We also investigated its function in endocytosis and revealed that endocytosis of SynA, a synaptobrevin ortholog that is known to be endocytosed at the subapical regions of hyphal tips in A. nidulans, did not occur when wspA expression was repressed. These results suggest that WspA plays roles in endocytosis at hyphal tips and polarity establishment during germination.

  7. Characterization of polyclonal antibodies against nonstructural protein 9 from the porcine reproductive and respiratory syndrome virus

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    Mengmeng ZHAO,Juanjuan QIAN,Jiexiong XIE,Tiantian CUI,Songling FENG,Guoqiang WANG,Ruining WANG,Guihong ZHANG

    2016-06-01

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS is considered to be one of the most important infectious diseases impacting the swine industry and is characterized by reproductive failure in late term gestation in sows and respiratory disease in pigs of all ages. The nonstructural protein 9 gene, Nsp9, encoding the RNA-dependent RNA polymerase, is generally regarded as fairly conserved when compared to other viral proteins. Antibodies against Nsp9 will be of great importance for the diagnosis and treatment of the causal agent, PRRS virus. A study was undertaken to generate polyclonal antibodies against the immunodominant Nsp9. For this purpose, the Nsp9 was expressed in Escherichia coli and subsequently used as an antigen to immunize New Zealand rabbits. Antiserum was identified via an indirect ELISA, and then verified based on the ability to react with both naturally and artificially expressed Nsp9. Results of virus neutralization test showed that this antiserum could not neutralize the PRRSV. Nevertheless, this antiserum as a diagnostic core reagent should prove invaluable for further investigations into the mechanism of PRRS pathogenesis.

  8. Sex difference in the association of metabolic syndrome with high sensitivity C-reactive protein in a Taiwanese population

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    Lin Wen-Yuan

    2010-07-01

    Full Text Available Abstract Background Although sex differences have been reported for associations between components of metabolic syndrome and inflammation, the question of whether there is an effect modification by sex in the association between inflammation and metabolic syndrome has not been investigated in detail. Therefore, the aim of this study was to compare associations of high sensitivity C-creative protein (hs-CRP with metabolic syndrome and its components between men and women. Methods A total of 1,305 subjects aged 40 years and over were recruited in 2004 in a metropolitan city in Taiwan. The biochemical indices, such as hs-CRP, fasting glucose levels, lipid profiles, urinary albumin, urinary creatinine and anthropometric indices, were measured. Metabolic syndrome was defined using the American Heart Association and the National Heart, lung and Blood Institute (AHA/NHLBI definition. The relationship between metabolic syndrome and hs-CRP was examined using multivariate logistic regression analysis. Results After adjustment for age and lifestyle factors including smoking, and alcohol intake, elevated concentrations of hs-CRP showed a stronger association with metabolic syndrome in women (odds ratio comparing tertile extremes 4.80 [95% CI: 3.31-6.97] than in men (2.30 [1.65-3.21]. The p value for the sex interaction was 0.002. All components were more strongly associated with metabolic syndrome in women than in men, and all sex interactions were significant except for hypertension. Conclusions Our data suggest that inflammatory processes may be of particular importance in the pathogenesis of metabolic syndrome in women.

  9. Draft Genome Sequence of the Toxic Bloom-Forming Cyanobacterium Aphanizomenon flos-aquae NIES-81

    OpenAIRE

    Cao, Huansheng; Shimura, Yohei; Masanobu, Kawachi; Yin, Yanbin

    2014-01-01

    Aphanizomenon flos-aquae is a toxic filamentous cyanobacterium that causes water blooms in freshwaters across the globe. We present the draft genome sequence of the A. flos-aquae strain NIES-81, which was determined by 454 pyrosequencing technology. The draft genome is ~5.7 Mb, containing 5,802 predicted protein-coding genes and 58 RNA genes, with a G+C content of 38.5%.

  10. Draft Genome Sequence of the Toxic Bloom-Forming Cyanobacterium Aphanizomenon flos-aquae NIES-81.

    Science.gov (United States)

    Cao, Huansheng; Shimura, Yohei; Masanobu, Kawachi; Yin, Yanbin

    2014-02-13

    Aphanizomenon flos-aquae is a toxic filamentous cyanobacterium that causes water blooms in freshwaters across the globe. We present the draft genome sequence of the A. flos-aquae strain NIES-81, which was determined by 454 pyrosequencing technology. The draft genome is ~5.7 Mb, containing 5,802 predicted protein-coding genes and 58 RNA genes, with a G+C content of 38.5%.

  11. Nitrogenous nutrients promote the growth and toxicity of Dinophysis acuminata during estuarine bloom events.

    Science.gov (United States)

    Hattenrath-Lehmann, Theresa K; Marcoval, Maria A; Mittlesdorf, Heidi; Goleski, Jennifer A; Wang, Zhihong; Haynes, Bennie; Morton, Steve L; Gobler, Christopher J

    2015-01-01

    Diarrhetic Shellfish Poisoning (DSP) is a globally significant human health syndrome most commonly caused by dinoflagellates within the genus Dinophysis. While blooms of harmful algae have frequently been linked to excessive nutrient loading, Dinophysis is a mixotrophic alga whose growth is typically associated with prey availability. Consequently, field studies of Dinophysis and nutrients have been rare. Here, the temporal dynamics of Dinophysis acuminata blooms, DSP toxins, and nutrients (nitrate, ammonium, phosphate, silicate, organic compounds) were examined over four years within two New York estuaries (Meetinghouse Creek and Northport Bay). Further, changes in the abundance and toxicity of D. acuminata were assessed during a series of nutrient amendment experiments performed over a three year period. During the study, Dinophysis acuminata blooms exceeding one million cells L-1 were observed in both estuaries. Highly significant (pnutrients significantly enhanced D. acuminata densities in nearly all (13 of 14) experiments performed. Ammonium significantly increased cell densities in 10 of 11 experiments, while glutamine significantly enhanced cellular DSP content in 4 of 5 experiments examining this compound. Nutrients may have directly or indirectly enhanced D. acuminata abundances as densities of this mixotroph during experiments were significantly correlated with multiple members of the planktonic community (phytoflagellates and Mesodinium). Collectively, this study demonstrates that nutrient loading and more specifically N-loading promotes the growth and toxicity of D. acuminata populations in coastal zones.

  12. Bloom Helicase and DNA Topoisomerase IIIα Are Involved in the Dissolution of Sister Chromatids

    OpenAIRE

    Seki, Masayuki; Nakagawa, Takayuki; Seki, Takahiko; Kato, Genta; Tada, Shusuke; TAKAHASHI, Yuriko; Yoshimura, Akari; Kobayashi, Takayuki; Aoki, Ayako; Otsuki, Makoto; Felix A Habermann; Tanabe, Hideyuki; Ishii, Yutaka; Enomoto, Takemi

    2006-01-01

    Bloom's syndrome (BS) is an autosomal disorder characterized by predisposition to a wide variety of cancers. The gene product whose mutation leads to BS is the RecQ family helicase BLM, which forms a complex with DNA topoisomerase IIIα (Top3α). However, the physiological relevance of the interaction between BLM and Top3α within the cell remains unclear. We show here that Top3α depletion causes accumulation of cells in G2 phase, enlargement of nuclei, and chromosome gaps and breaks that occur ...

  13. Biology in bloom: implementing Bloom's Taxonomy to enhance student learning in biology.

    Science.gov (United States)

    Crowe, Alison; Dirks, Clarissa; Wenderoth, Mary Pat

    2008-01-01

    We developed the Blooming Biology Tool (BBT), an assessment tool based on Bloom's Taxonomy, to assist science faculty in better aligning their assessments with their teaching activities and to help students enhance their study skills and metacognition. The work presented here shows how assessment tools, such as the BBT, can be used to guide and enhance teaching and student learning in a discipline-specific manner in postsecondary education. The BBT was first designed and extensively tested for a study in which we ranked almost 600 science questions from college life science exams and standardized tests. The BBT was then implemented in three different collegiate settings. Implementation of the BBT helped us to adjust our teaching to better enhance our students' current mastery of the material, design questions at higher cognitive skills levels, and assist students in studying for college-level exams and in writing study questions at higher levels of Bloom's Taxonomy. From this work we also created a suite of complementary tools that can assist biology faculty in creating classroom materials and exams at the appropriate level of Bloom's Taxonomy and students to successfully develop and answer questions that require higher-order cognitive skills.

  14. The Deletable Bloom filter: A new member of the Bloom family

    CERN Document Server

    Rothenberg, Christian Esteve; Verdi, Fabio L; Magalhaes, Mauricio F

    2010-01-01

    We introduce the Deletable Bloom filter (DlBF) as a new spin on the popular data structure based on compactly encoding the information of where collisions happen when inserting elements. The DlBF design enables false-negative-free deletions at a fraction of the cost in memory consumption, which turns to be appealing for certain probabilistic filter applications.

  15. High sensitivity C-reactive protein in airline pilots with metabolic syndrome.

    Science.gov (United States)

    Alonso-Rodríguez, César; Medina-Font, Juan

    2012-05-01

    Airline pilots belong to a relatively high-income, healthy population, with sedentary behavior during their flight activity, who often eat unsuitable meals. We assessed the prevalence of metabolic syndrome (MS) and the levels of high sensitivity C-reactive protein (hs-CRP) in a population of airline pilot in order to study a possible relationship between the hs-CRP and MS. MS was established according to the National Cholesterol Education Program, Adult Treatment Panel III. hs-CRP was classified into three categories: Low 3 mg x L(-1). The prevalence of MS was 14.8%. The hs-CRP level in the population studied was 1.68 +/- 1.79 mg x L(-1). hs-CRP significantly increased with age. The pilots with MS presented significantly higher hs-CRP levels (median = 1.9 with an interquartile range (IQR) = 2.5 mg x L(-1)) than the pilots without MS (median = 0.9 and IQR = 1.275 mg x L(-1)). MS significantly increased in the groups with high hs-CRP in comparison with pilots with intermediate hs-CRP levels and with those with low hs-CRP levels. A similar association was found between the levels of hs-CRP and the prevalence of MS in the three age groups. The levels of hs-CRP increased in pilots as they presented greater numbers of MS diagnostic criteria. hs-CRP rises significantly in pilots of increasing age, in pilots with MS as compared to those without the syndrome, and in pilots as they present greater numbers of MS diagnostic criteria. The prevalence of MS increased among the groups with higher levels of hs-CRP.

  16. Metabolic syndrome: prevalence, associated factors, and C-reactive protein: the MADRIC (MADrid RIesgo Cardiovascular) Study.

    Science.gov (United States)

    Martínez, Maria A; Puig, Juan G; Mora, Marta; Aragón, Rosa; O'Dogherty, Pascual; Antón, José L; Sánchez-Villares, Teresa; Rubio, José M; Rosado, Javier; Torres, Rosa; Marcos, Joaquín; Pallardo, Luis F; Banegas, José R

    2008-09-01

    The metabolic syndrome (MS) is defined by the clustering of a number of cardiovascular risk factors. The aims of the present study were to estimate the prevalence of MS in Madrid (Spain) by 2 definitions and to investigate its relationship with several sociodemographic factors and C-reactive protein (CRP) levels. This was a cross-sectional population study, and participants were 1344 subjects aged 31 to 70 years. Clinical evaluation included data on sociodemographic and cardiovascular background, physical examination, fasting glucose, triglycerides, and high-density lipoprotein cholesterol. The CRP levels were determined in a subgroup of 843 subjects. The diagnosis of MS was made according to the 2005 Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF) definitions. The age- and sex-adjusted prevalence of MS was 24.6% (95% confidence interval [CI], 22.3%-26.9%) using the ATP III definition and 30.9% (95% CI, 28.4%-33.3%) using the International Diabetes Federation definition. The overall agreement rate was 91.5% (kappa = 0.80; 95% CI, 0.76-0.83). Prevalence figures by both definitions were higher in men than in women and increased with age. Male sex, older age, low educational level, and physical inactivity were all determinants of ATP III-defined MS. The presence of MS or any of its components was associated with high CRP levels. In a logistic regression analysis, low educational level and waist circumference were the best predictors for high CRP level. The prevalence of MS in the Madrid region is one of the highest in Europe and confirms the strong Spanish regional variability in this syndrome frequency. Some sociodemographic and lifestyle factors, particularly educational level, are predictors for MS and high CRP levels.

  17. Epigenetic Regulation in Amyloid Precursor Protein with Genomic Rearrangements and the Lesch-Nyhan Syndrome.

    Science.gov (United States)

    Nguyen, Khue Vu

    2015-01-01

    Recently, epigenetic regulation of alternative APP pre-mRNA splicing in the Lesch-Nyhan syndrome (LNS) has been studied (see Ref. 7) and showed for the first time, the presence of several APP-mRNA isoforms encoding divers APP protein isoforms ranging from 120 to 770 amino acids (with or without mutations and/or deletions). Here, by continuing on this work, I identified, for the first time new APP-mRNA isoforms with a deletion followed by an insertion (INDELS) in LNS and LNVs patients: c.19_2295delinsG166TT…GAGTCC…CTTAGTC…TCT489,p.Leu7Valfs*2;c.19_2295 delinsG169TT…GAGACC…CTTGGTC…TCT492,p.Leu7Valfs*2;and c.16_2313delinsG84CC…CAT616,p.Leu7Hisfs*45. A role of genomic rearrangements of APP gene via the Fork Stalling and Template Switching (FoSTeS) mechanism leading to INDELS was suggested. Epistasis between mutated HPRT1 and APP genes could be one of the factors of epigenetic modifications responsible for genomic rearrangements of APP gene. My findings accounted for epigenetic mechanism in the regulation of alternative APP pre-mRNA splicing as well as for epigenetic control of genomic rearrangements of APP gene may provide therefore new directions not only for investigating the role of APP in neuropathology associated with HGprt-deficiency in LNS and LNVs patients but also for the research in neurodevelopmental and neurodegenerative disorders by which APP gene involved in the pathogenesis of the diseases such as autism, fragile X syndrome (FXS), and Alzheimer's disease (AD) with its diversity and complexity, especially for sporadic form of AD (SAD). An accurate quantification of various APP-mRNA isoforms in brain tissues for detection of initial pathological changes or pathology development is needed and antisense drugs are the potential treatments.

  18. C-reactive protein as a predictor of adverse outcome in patients with acute coronary syndrome

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    A S Sheikh

    2012-01-01

    Full Text Available Background and Objectives: The acute-phase reactant C-reactive protein (CRP has been shown to reflect systemic and vascular inflammation and to predict future cardiovascular events. The objective of this study was to evaluate the prognostic value of CRP in predicting cardiovascular outcome in patients presenting with acute coronary syndromes. Patients and Methods: This prospective, single-centered study was carried out by the Department of Pathology in collaboration with the Department of Cardiology, Bolan Medical College Complex Quetta, Balochistan, Pakistan from January 2009 to December 2009. We studied 963 consecutive patients presenting with chest pain to Accident and Emergency Department. Patients were divided into four groups. Group-1 comprised patients with unstable angina; group-2 included patients with acute ST elevation myocardial infarction (STEMI; group-3 comprised patients with Non-ST elevation myocardial infarction (Non-STEMI and group-4 was the control group. All four groups were followed-up for 90 days for occurrence of cardiovascular events. Results: The CRP was elevated (>3 mg/L among 27.6% patients in Group-1; 70.9% in group- 2; 77.9% in group-3 and 5.3% in the control group. Among cases with elevated CRP, 92.1% had a cardiac event compared to 34.3% among patients with CRP £3 mg/L (P < 0.0001. The mortality was significantly higher (P < 0.0001 in group-2 (8.9% and group-3 (11.9% as compared to group-1 (2.1%. There was no cardiac event or mortality in Group-4. Conclusions: Elevated CRP is a predictor of adverse outcome in patients with acute coronary syndromes and helps in identifying patients who may be at risk of cardiovascular complications.

  19. Characterization of the Drosophila ortholog of the human Usher Syndrome type 1G protein sans.

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    Fabio Demontis

    Full Text Available BACKGROUND: The Usher syndrome (USH is the most frequent deaf-blindness hereditary disease in humans. Deafness is attributed to the disorganization of stereocilia in the inner ear. USH1, the most severe subtype, is associated with mutations in genes encoding myosin VIIa, harmonin, cadherin 23, protocadherin 15, and sans. Myosin VIIa, harmonin, cadherin 23, and protocadherin 15 physically interact in vitro and localize to stereocilia tips in vivo, indicating that they form functional complexes. Sans, in contrast, localizes to vesicle-like structures beneath the apical membrane of stereocilia-displaying hair cells. How mutations in sans result in deafness and blindness is not well understood. Orthologs of myosin VIIa and protocadherin 15 have been identified in Drosophila melanogaster and their genetic analysis has identified essential roles in auditory perception and microvilli morphogenesis, respectively. PRINCIPAL FINDINGS: Here, we have identified and characterized the Drosophila ortholog of human sans. Drosophila Sans is expressed in tubular organs of the embryo, in lens-secreting cone cells of the adult eye, and in microvilli-displaying follicle cells during oogenesis. Sans mutants are viable, fertile, and mutant follicle cells appear to form microvilli, indicating that Sans is dispensable for fly development and microvilli morphogenesis in the follicle epithelium. In follicle cells, Sans protein localizes, similar to its vertebrate ortholog, to intracellular punctate structures, which we have identified as early endosomes associated with the syntaxin Avalanche. CONCLUSIONS: Our work is consistent with an evolutionary conserved function of Sans in vesicle trafficking. Furthermore it provides a significant basis for further understanding of the role of this Usher syndrome ortholog in development and disease.

  20. Association of the Hermansky-Pudlak syndrome type-3 protein with clathrin

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    Gahl William A

    2005-09-01

    Full Text Available Abstract Background Hermansky-Pudlak syndrome (HPS is a disorder of lysosome-related organelle biogenesis characterized by oculocutaneous albinism and prolonged bleeding. These clinical findings reflect defects in the formation of melanosomes in melanocytes and dense bodies in platelets. HPS type-3 (HPS-3 results from mutations in the HPS3 gene, which encodes a 1004 amino acid protein of unknown function that contains a predicted clathrin-binding motif (LLDFE at residues 172–176. Results Clathrin was co-immunoprecipitated by HPS3 antibodies from normal but not HPS3 null melanocytes. Normal melanocytes expressing a GFP-HPS3 fusion protein demonstrated partial co-localization of GFP-HPS3 with clathrin following a 20°C temperature block. GFP-HPS3 in which the predicted clathrin-binding domain of HPS3 was mutated (GFP-HPS3-delCBD did not co-localize with clathrin under the same conditions. Immunoelectron microscopy of normal melanocytes expressing GFP-HPS3 showed co-localization of GFP-HPS3 with clathrin, predominantly on small vesicles in the perinuclear region. In contrast, GFP-HPS3-delCBD did not co-localize with clathrin and exhibited a largely cytoplasmic distribution. Conclusion HPS3 associates with clathrin, predominantly on small clathrin-containing vesicles in the perinuclear region. This association most likely occurs directly via a functional clathrin-binding domain in HPS3. These results suggest a role for HPS3 and its protein complex, BLOC-2, in vesicle formation and trafficking.

  1. Fecal assays detect hypersensitivity to cow's milk protein and gluten in adults with irritable bowel syndrome.

    Science.gov (United States)

    Carroccio, Antonio; Brusca, Ignazio; Mansueto, Pasquale; Soresi, Maurizio; D'Alcamo, Alberto; Ambrosiano, Giuseppe; Pepe, Ilenia; Iacono, Giuseppe; Lospalluti, Maria Letizia; La Chiusa, Stella M; Di Fede, Gaetana

    2011-11-01

    Some patients with irritable bowel syndrome (IBS)-like symptoms suffer from food hypersensitivity (FH); their symptoms improve when they are placed on elimination diets. No assays identify patients with FH with satisfactory levels of sensitivity. We determined the frequency of FH among patients with symptoms of IBS and the ability of fecal assays for tryptase, eosinophil cationic protein (ECP), or calprotectin to diagnose FH. The study included 160 patients with IBS, 40 patients with other gastrointestinal diseases, and 50 healthy individuals (controls). At the start of the study, patients completed a symptom severity questionnaire, fecal samples were assayed, and levels of specific immunoglobulin E were measured. Patients were observed for 4 weeks, placed on an elimination diet (without cow's milk and derivatives, wheat, egg, tomato, and chocolate) for 4 weeks, and kept a diet diary. Those who reported improvements after the elimination diet period were then diagnosed with FH, based on the results of a double-blind, placebo-controlled, oral food challenge (with cow's milk proteins and then with wheat proteins). Forty of the patients with IBS (25%) were found to have FH. Levels of fecal ECP and tryptase were significantly higher among patients with IBS and FH than those without FH. The ECP assay was the most accurate assay for diagnosis of FH, showing 65% sensitivity and 91% specificity. Twenty-five percent of patients with IBS have FH. These patients had increased levels of fecal ECP and tryptase, indicating that they might cause inflammation in patients with IBS. Fecal assays for ECP could be used to identify FH in patients with IBS. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis.

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    Marta L DeDiego

    2011-10-01

    Full Text Available Severe acute respiratory syndrome virus (SARS-CoV that lacks the envelope (E gene (rSARS-CoV-ΔE is attenuated in vivo. To identify factors that contribute to rSARS-CoV-ΔE attenuation, gene expression in cells infected by SARS-CoV with or without E gene was compared. Twenty-five stress response genes were preferentially upregulated during infection in the absence of the E gene. In addition, genes involved in signal transduction, transcription, cell metabolism, immunoregulation, inflammation, apoptosis and cell cycle and differentiation were differentially regulated in cells infected with rSARS-CoV with or without the E gene. Administration of E protein in trans reduced the stress response in cells infected with rSARS-CoV-ΔE or with respiratory syncytial virus, or treated with drugs, such as tunicamycin and thapsigargin that elicit cell stress by different mechanisms. In addition, SARS-CoV E protein down-regulated the signaling pathway inositol-requiring enzyme 1 (IRE-1 of the unfolded protein response, but not the PKR-like ER kinase (PERK or activating transcription factor 6 (ATF-6 pathways, and reduced cell apoptosis. Overall, the activation of the IRE-1 pathway was not able to restore cell homeostasis, and apoptosis was induced probably as a measure to protect the host by limiting virus production and dissemination. The expression of proinflammatory cytokines was reduced in rSARS-CoV-ΔE-infected cells compared to rSARS-CoV-infected cells, suggesting that the increase in stress responses and the reduction of inflammation in the absence of the E gene contributed to the attenuation of rSARS-CoV-ΔE.

  3. Proinflammatory proteins in female and male patients with primary antiphospholipid syndrome: preliminary data.

    Science.gov (United States)

    Bećarević, Mirjana; Ignjatović, Svetlana

    2016-10-01

    The latest classification criteria for the diagnosis of the antiphospholipid syndrome (APS, an autoimmune disease characterized by thromboses, miscarriages and presence of antiphospholipid antibodies (Abs)) emphasized that thrombotic manifestations of APS should be without any signs of an inflammatory process. However, atherosclerosis (a chronic inflammatory response to the accumulation of lipoproteins in the walls of arteries) and APS are characterized by some similar features. We evaluated whether proinflammatory proteins were associated with the features of the primary APS (PAPS). PAPS patients without obstetric complications and with impaired lipid profile were included in the study. Antiphospholipid antibodies, TNF-alpha, and apo(a) were determined by ELISA. Complement components and hsCRP were measured by immunonephelometry. Decreased C3c was observed in female patients with increased titers of IgG anti-β2gpI (χ(2) = 3.939, P = 0.047) and in male patients with increased IgM anticardiolipin Abs (χ(2) = 4.286, P = 0.038). Pulmonary emboli were associated with interleukin (IL)-6 in male (χ(2) = 6.519, P = 0.011) and in female (χ(2) = 10.405, P = 0.001) patients. Cerebrovascular insults were associated with LDL-cholesterol (P = 0.05, 95 % CI: 1.003 - 12.739) in female and with apo(a) (P = 0.016, 95 % CI: 0.000-0.003) in male patients. Older female patients had increased LDL-cholesterol levels and frequency of myocardial infarctions. Proinflammatory proteins were associated with features of primary APS. No real gender differences in regard to proinflammatory protein levels were observed. Premenopausal state of female PAPS patients confers lower cardiovascular risk.

  4. An active learning approach to Bloom's Taxonomy.

    Science.gov (United States)

    Weigel, Fred K; Bonica, Mark

    2014-01-01

    As educators strive toward improving student learning outcomes, many find it difficult to instill their students with a deep understanding of the material the instructors share. One challenge lies in how to provide the material with a meaningful and engaging method that maximizes student understanding and synthesis. By following a simple strategy involving Active Learning across the 3 primary domains of Bloom's Taxonomy (cognitive, affective, and psychomotor), instructors can dramatically improve the quality of the lesson and help students retain and understand the information. By applying our strategy, instructors can engage their students at a deeper level and may even find themselves enjoying the process more.

  5. Chromosomal protein HMG-14 gene maps to the Down syndrome region of human chromosome 21 and is overexpressed in mouse trisomy 16

    Energy Technology Data Exchange (ETDEWEB)

    Pash, J.; Popescu, N.; Matocha, M.; Rapoport, S.; Bustin, M. (National Institutes of Health, Bethesda, MD (USA))

    1990-05-01

    The gene for human high-mobility-group (HMG) chromosomal protein HMG-14 is located in region 21q22.3, a region associated with the pathogenesis of Down syndrome, one of the most prevalent human birth defects. The expression of this gene is analyzed in mouse embryos that are trisomic in chromosome 16 and are considered to be an animal model for Down syndrome. RNA blot-hybridization analysis and detailed analysis of HMG-14 protein levels indicate that mouse trisomy 16 embryos have approximately 1.5 times more HMG-14 mRNA and protein than their normal littermates, suggesting a direct gene dosage effect. The HMG-14 gene may be an additional marker for the Down syndrome. Chromosomal protein HMG-14 is a nucleosomal binding protein that may confer distinct properties to the chromatin structure of transcriptionally active genes and therefore may be a contributing factor in the etiology of the syndrome.

  6. High-sensitivity C-reactive protein predicts target organ damage in Chinese patients with metabolic syndrome

    DEFF Research Database (Denmark)

    Zhao, Zhigang; Nie, Hai; He, Hongbo

    2007-01-01

    with metabolic syndrome. A total of 1082 consecutive patients of Chinese origin were screened for the presence of metabolic syndrome according to the National Cholesterol Education Program's Adult Treatment Panel III. High-sensitivity C-reactive protein and target organ damage, including cardiac hypertrophy......Observational studies established high-sensitivity C-reactive protein as a risk factor for cardiovascular events in the general population. The goal of this study was to determine the relationship between target organ damage and high-sensitivity C-reactive protein in a cohort of Chinese patients......, carotid intima-media thickness, and renal impairment, were investigated. The median (25th and 75th percentiles) of high-sensitivity C-reactive protein in 619 patients with metabolic syndrome was 2.42 mg/L (0.75 and 3.66 mg/L) compared with 1.13 mg/L (0.51 and 2.46 mg/L) among 463 control subjects (P

  7. Distribution of Wfs1 protein in the central nervous system of the mouse and its relation to clinical symptoms of the Wolfram syndrome

    DEFF Research Database (Denmark)

    Luuk, H.; Koks, S.; Plaas, M.;

    2008-01-01

    Mutations in the coding region of the WFS1 gene cause Wolfram syndrome, a rare multisystem neurodegenerative disorder of autosomal recessive inheritance. Patients with Wolfram syndrome display considerable clinical pleiomorphism, and symptoms such as neurological complications and psychiatric dis...... and psychiatric symptoms found in Wolfram syndrome. Enrichment of Wfs1 protein in the central extended amygdala suggests a role in the modulation of anxiety and fear Udgivelsesdato: 2008/8/20...

  8. Genetics Home Reference: Ochoa syndrome

    Science.gov (United States)

    ... PubMed (1 link) PubMed OMIM (1 link) UROFACIAL SYNDROME 1 Sources for This Page Al Badr W, Al Bader S, Otto E, Hildebrandt F, Ackley T, Peng W, Xu J, Li J, Owens KM, Bloom D, Innis JW. Exome capture and massively parallel ...

  9. WATER BLOOM OF BLUEGREEN ALGE IN CARP FISHPOUNDS

    Directory of Open Access Journals (Sweden)

    Melita Mihaljević

    1996-03-01

    Full Text Available The massive development of bluegreen algae (Cyanophyta/Cyanobacteria, the so--called water bloom, is a frequent phenomenon in fishpond ecosystems. This study analyses water bloom development in three carp fishponds owned by a fishbreeding company at Donji Miholjac (Croatia, where one-year-old carps (Cyprinus carpio , were bred in defferent fishstock densities. Analyses of physicallychemical properties of water and phytoplankton biomass were per- formed in fortnight intervals from May till October, 1992. In all there investigated fishponds the water bloom of bluegreen algae developed, but at a different time and showing a different qualitative composition. In the fishpond with fishstock density of 250 kg/ha water bloom consisted of the species Aphanizomenon flos-aquae, and the biggest biomass (131.92 mg/I was found in August. In the fishpond with fishstock density of 437 kg/ha a water bloom consisting of species from the genues Anabaena and species Aphanizomenon flos-aquae developed at the end of July. In the fishpond with the so--called intensive breeding (fishstock density of 750 kg/ha water bloom of the species Microcystis aeruginosa developed as late as September. The beginning of water bloom development was caused by the low value (lower than 7 of the ratio between the quantities of total phosphorus and total nitrogen. However, the qualitative composition of water bloom was influenced by one-year-old carp fingerlings density.

  10. Requirements for forecasting harmful algal blooms in the Benguela

    CSIR Research Space (South Africa)

    Bernard, S

    2006-01-01

    Full Text Available The Benguela system suffers from the frequent occurence of a variety of harmful algal blooms (HABs).These blooms can have severe negative impacts on local marine ecosystems and communities, in addition to commercial marine concerns such as rock...

  11. The Self According to Allan Bloom and Charles Reich.

    Science.gov (United States)

    Aspy, David N.; Aspy, Cheryl B.

    1998-01-01

    Discusses the works of Charles Reich and Allan Bloom that have helped to shape current social and political debate concerning self theory. Both Reich and Bloom were concerned with the relationship between self and environment. Argues that it is important to insure that its cultural role of self theory is clearly interpreted and applied. (MKA)

  12. The Evolution of Educational Objectives: Bloom's Taxonomy and beyond

    Science.gov (United States)

    Fallahi, Carolyn R.; LaMonaca, Frank H., Jr.

    2009-01-01

    It is crucial for teachers to communicate effectively about educational objectives to students, colleagues, and others in education. In 1956, Bloom developed a cognitive learning taxonomy to enhance communication between college examiners. The Bloom taxonomy consists of 6 hierarchical levels of learning (knowledge, comprehension, application,…

  13. Use of Bloom's Taxonomy in Developing Reading Comprehension Specifications

    Science.gov (United States)

    Luebke, Stephen; Lorie, James

    2013-01-01

    This article is a brief account of the use of Bloom's Taxonomy of Educational Objectives (Bloom, Engelhart, Furst, Hill, & Krathwohl, 1956) by staff of the Law School Admission Council in the 1990 development of redesigned specifications for the Reading Comprehension section of the Law School Admission Test. Summary item statistics for the…

  14. Treatment of Metabolic syndrome by combination of physical activity and diet needs an optimal protein intake: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Dutheil Frédéric

    2012-09-01

    Full Text Available Abstract Background The recommended dietary allowance (RDA for protein intake has been set at 1.0-1.3 g/kg/day for senior. To date, no consensus exists on the lower threshold intake (LTI = RDA/1.3 for the protein intake (PI needed in senior patients ongoing both combined caloric restriction and physical activity treatment for metabolic syndrome. Considering that age, caloric restriction and exercise are three increasing factors of protein need, this study was dedicated to determine the minimal PI in this situation, through the determination of albuminemia that is the blood marker of protein homeostasis. Methods Twenty eight subjects (19 M, 9 F, 61.8 ± 6.5 years, BMI 33.4 ± 4.1 kg/m2 with metabolic syndrome completed a three-week residential programme (Day 0 to Day 21 controlled for nutrition (energy balance of −500 kcal/day and physical activity (3.5 hours/day. Patients were randomly assigned in two groups: Normal-PI (NPI: 1.0 g/kg/day and High-PI (HPI: 1.2 g/kg/day. Then, patients returned home and were followed for six months. Albuminemia was measured at D0, D21, D90 and D180. Results At baseline, PI was spontaneously 1.0 g/kg/day for both groups. Albuminemia was 40.6 g/l for NPI and 40.8 g/l for HPI. A marginal protein under-nutrition appeared in NPI with a decreased albuminemia at D90 below 35 g/l (34.3 versus 41.5 g/l for HPI, p  Conclusion During the treatment based on restricted diet and exercise in senior people with metabolic syndrome, the lower threshold intake for protein must be set at 1.2 g/kg/day to maintain blood protein homeostasis.

  15. Severe acute respiratory syndrome coronavirus protein 6 mediates ubiquitin-dependent proteosomal degradation of N-Myc(and STAT) interactor

    Institute of Scientific and Technical Information of China (English)

    Weijia; Cheng; Shiyou; Chen; Ruiling; Li; Yu; Chen; Min; Wang; Deyin; Guo

    2015-01-01

    Severe acute respiratory syndrome coronavirus(SARS-Co V) encodes eight accessory proteins, the functions of which are not yet fully understood. SARS-Co V protein 6(P6) is one of the previously studied accessory proteins that have been documented to enhance viral replication and suppress host interferon(IFN) signaling pathways. Through yeast two-hybrid screening, we identified eight potential cellular P6-interacting proteins from a human spleen c DNA library. For further investigation, we targeted the IFN signaling pathway-mediating protein, N-Myc(and STAT) interactor(Nmi). Its interaction with P6 was confirmed within cells. The results showed that P6 can promote the ubiquitin-dependent proteosomal degradation of Nmi. This study revealed a new mechanism of SARS-Co V P6 in limiting the IFN signaling to promote SARS-Co V survival in host cells.

  16. DSCR2, a Down syndrome critical region protein, is localized to the endoplasmic reticulum of mammalian cells

    Directory of Open Access Journals (Sweden)

    PA Possik

    2009-06-01

    Full Text Available We used immunocytochemical and fluorescence assays to investigate the subcellular location of the protein encoded by Down syndrome critical region gene 2 (DSCR2 in transfected cells. It was previously suggested that DSCR2 is located in the plasma membrane as an integral membrane protein. Interestingly, we observed this protein in the endoplasmic reticulum (ER of cells.We also studied whether the truncated forms of DSCR2 showed different subcellular distributions. Our observations indicate that DSCR2 probably is not inserted into the membrane of the endoplasmic reticulum since the fragments lacking the predicted transmembrane (TM helices remained associated with the ER. Our analyses suggest that, although DSCR2 is associated with the endoplasmic reticulum, it is not an integral membrane protein and it is maintained on the cytoplasmic side of the ER by indirect interaction with the ER membrane or with another protein.

  17. Regenerating Gene Protein as a Novel Autoantigen in the Pathogenesis of Sjögren’s Syndrome

    Directory of Open Access Journals (Sweden)

    Takashi Fujimoto

    2015-12-01

    Full Text Available Sjögren’s syndrome, an autoimmune disease characterized by exocrine gland dysfunction leading to dry mouth and dry eye diseases, is typified by lymphoplasmacytic infiltrations and a progressive destruction of the salivary and lacrimal glands. Despite an ever-increasing focus on identifying the underlying etiology of Sjögren’s syndrome, the factors that initiate this autoimmune disease and the mechanisms that cause the subsequent exocrine gland dysfunction remain a mystery. The original explanatory concept for the pathogenesis of Sjögren’s syndrome proposed a specific, self-perpetuating, immune-mediated loss of acinar and ductal cells as the principal cause of salivary gland dysfunction. We highlight the possible involvement of regenerating gene (Reg in the regeneration and destruction of salivary gland acinar and ductal cells in Sjögren’s syndrome. The Reg gene was originally isolated as a gene specifically overexpressed in regenerating pancreatic islets and constitutes a growth factor family (Reg family. We describe how salivary gland dysfunction is initiated and maintained and how it can be regenerated or progressed, mediated by the Reg gene, Reg protein, and anti-REG autoantibodies in Sjögren’s syndrome.

  18. Margalef's mandala and phytoplankton bloom strategies

    Science.gov (United States)

    Wyatt, Timothy

    2014-03-01

    Margalef's mandala maps phytoplankton species into a phase space defined by turbulence (A) and nutrient concentrations (Ni); these are the hard axes. The permutations of high and low A and high and low Ni divide the space into four domains. Soft axes indicate some ecological dynamics. A main sequence shows the normal course of phytoplankton succession; the r-K axis of MacArthur and Wilson runs parallel to it. An alternative successional sequence leads to the low A-high Ni domain into which many red tide species are mapped. Astronomical and biological time are implicit. A mathematical transformation of the mandala (rotation) links it to the classical bloom models of Sverdrup (time) and Kierstead and Slobodkin (space). Both rarity and the propensity to form red tides are considered to be species characters, meaning that maximum population abundance can be a target of natural selection. Equally, both the unpredictable appearance of bloom species and their short-lived appearances may be species characters. There may be a correlation too between these features and long-lived dormant stages in the life-cycle; then the vegetative planktonic phase is the 'weak link' in the life-cycle. Red tides are thus due to species which have evolved suites of traits which result in specific demographic strategies.

  19. RECOMMENDATION SYSTEM USING BLOOM FILTER IN MAPREDUCE

    Directory of Open Access Journals (Sweden)

    Reena Pagare

    2013-11-01

    Full Text Available Many clients like to use the Web to discover product details in the form of online reviews. The reviews are provided by other clients and specialists. Recommender systems provide an important response to the information overload problem as it presents users more practical and personalized information facilities. Collaborative filtering methods are vital component in recommender systems as they generate high-quality recommendations by influencing the likings of society of similar users. The collaborative filtering method has assumption that people having same tastes choose the same items. The conventional collaborative filtering system has drawbacks as sparse data problem & lack of scalability. A new recommender system is required to deal with the sparse data problem & produce high quality recommendations in large scale mobile environment. MapReduce is a programming model which is widely used for large-scale data analysis. The described algorithm of recommendation mechanism for mobile commerce is user based collaborative filtering using MapReduce which reduces scalability problem in conventional CF system. One of the essential operations for the data analysis is join operation. But MapReduce is not very competent to execute the join operation as it always uses all records in the datasets where only small fraction of datasets are applicable for the join operation. This problem can be reduced by applying bloomjoin algorithm. The bloom filters are constructed and used to filter out redundant intermediate records. The proposed algorithm using bloom filter will reduce the number of intermediate results and will improve the join performance.

  20. Phytoplankton Bloom in North Sea off Scotland

    Science.gov (United States)

    2008-01-01

    The northern and western highlands of Scotland were still winter-brown and even dusted with snow in places, but the waters of the North Sea were blooming with phytoplankton on May 8, 2008, when the Moderate Resolution Imaging Spectroradiometer (MODIS) on NASA's Aqua satellite passed over the region and captured this image. The tiny, plant-like organisms swirled in the waters off the country's east coast, coloring the shallow coastal waters shades of bright blue and green. Phytoplankton are tiny organisms--many are just a single cell--that use chlorophyll and other pigments to capture light for photosynthesis. Because these pigments absorb sunlight, they change the color of the light reflected from the sea surface back to the satellite. Scientists have used observations of 'ocean color' from satellites for more than 20 years to track worldwide patterns in phytoplankton blooms. Phytoplankton are important to the Earth system for a host of reasons, including their status as the base of the ocean food web. In the North Sea, they are the base of the food web that supports Scotland's commercial fisheries, including monkfish and herring. As photosynthesizers, they also play a crucial role in the carbon cycle, removing carbon dioxide from the atmosphere. Some oceanographers are concerned that rising ocean temperatures will slow phytoplankton growth rates, harming marine ecosystems and causing carbon dioxide to accumulate more rapidly in the atmosphere.

  1. Cysteine residues of the porcine reproductive and respiratory syndrome virus ORF5a protein are not essential for virus viability.

    Science.gov (United States)

    Sun, Lichang; Zhou, Yan; Liu, Runxia; Li, Yanhua; Gao, Fei; Wang, Xiaomin; Fan, Hongjie; Yuan, Shishan; Wei, Zuzhang; Tong, Guangzhi

    2015-02-02

    ORF5a protein was recently identified as a novel structural protein in porcine reproductive and respiratory syndrome virus (PRRSV). The ORF5a protein possesses two cysteines at positions 29 and 30 that are highly conserved among type 2 PRRSV. In this study, the significance of the ORF5a protein cysteine residues on virus replication was determined based on a type 2 PRRSV cDNA clone (pAJXM). Each cysteine was substituted by serine or glycine and the mutations were introduced into pAJXM. We found that the replacement of cysteine to glycine at position 30 was lethal for virus viability, but all serine mutant clones produced infectious progeny viruses. This data indicated that cysteine residues in the ORF5a protein were not essential for replication of type 2 PRRSV. The bimolecular fluorescence complementation (BiFC) and Co-immunoprecipitation (Co-IP) assay were used to study ORF5a protein interacted with other enveloped proteins. These results showed that ORF5a protein interacted non-covalently with itself and interacted with GP4 and 2b protein. The replacement of cysteine to glycine at position 30 affected the ORF5a protein interacted non-covalently with itself, which may account for the lethal phenotype of mutants carrying substitution of cysteine to glycine at position 30.

  2. Novel Roles of Amyloid-Beta Protein Precursor Metabolites in Fragile X Syndrome and Autism

    Science.gov (United States)

    Westmark, Cara J.; Sokol, Deborah K.; Maloney, Bryan; Lahiri, Debomoy K.

    2017-01-01

    Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and is associated with up to 5% of autism cases. Several promising drugs are in preclinical testing for FXS; however, bench-to-bedside plans for the clinic are severely limited due to lack of validated biomarkers and outcome measures. Published work from our laboratories has demonstrated altered levels of amyloid-beta (Aβ) protein precursor (APP) and its metabolites in FXS and idiopathic autism. Westmark and colleagues have focused on β-secretase (amyloidogenic) processing and the accumulation of Aβ peptides in adult FXS models while Lahiri and Sokol have studied α-secretase (nonamyloidogenic or anabolic) processing and altered levels of sAPPα and Aβ in pediatric autism and FXS. Thus, our groups have hypothesized a pivotal role for these Alzheimer’s disease (AD)-related proteins in the neurodevelopmental disorders of FXS and autism. In this review, we discuss the contribution of APP metabolites to FXS and autism pathogenesis as well as the potential use of these metabolites as blood-based biomarkers and therapeutic targets. Our future focus is to identify key underlying mechanisms through which APP metabolites contribute to FXS and autism condition-to-disease pathology. Positive outcomes will support utilizing APP metabolites as blood-based biomarkers in clinical trials as well as testing drugs that modulate APP processing as potential disease therapeutics. Our studies to understand the role of APP metabolites in developmental conditions such as FXS and autism are a quantum leap for the neuroscience field, which has traditionally restricted any role of APP to AD and aging. PMID:27573877

  3. SNX27, a protein involved in down syndrome, regulates GPR17 trafficking and oligodendrocyte differentiation.

    Science.gov (United States)

    Meraviglia, Veronica; Ulivi, Alessandro Francesco; Boccazzi, Marta; Valenza, Fabiola; Fratangeli, Alessandra; Passafaro, Maria; Lecca, Davide; Stagni, Fiorenza; Giacomini, Andrea; Bartesaghi, Renata; Abbracchio, Maria P; Ceruti, Stefania; Rosa, Patrizia

    2016-08-01

    The G protein-coupled receptor 17 (GPR17) plays crucial roles in myelination. It is highly expressed during transition of oligodendrocyte progenitor cells to immature oligodendrocytes, but, after this stage, it must be down-regulated to allow generation of mature myelinating cells. After endocytosis, GPR17 is sorted into lysosomes for degradation or recycled to the plasma membrane. Balance between degradation and recycling is important for modulation of receptor levels at the cell surface and thus for the silencing/activation of GPR17-signaling pathways that, in turn, affect oligodendrocyte differentiation. The molecular mechanisms at the basis of these processes are still partially unknown and their characterization will allow a better understanding of myelination and provide cues to interpret the consequences of GPR17 dysfunction in diseases. Here, we demonstrate that the endocytic trafficking of GPR17 is mediated by the interaction of a type I PDZ-binding motif located at the C-terminus of the receptor and SNX27, a recently identified protein of the endosome-associated retromer complex and whose functions in oligodendrocytes have never been studied. SNX27 knock-down significantly reduces GPR17 plasma membrane recycling in differentiating oligodendrocytes while accelerating cells' terminal maturation. Interestingly, trisomy-linked down-regulation of SNX27 expression in the brain of Ts65Dn mice, a model of Down syndrome, correlates with a decrease in GPR17(+) cells and an increase in mature oligodendrocytes, which, however, fail in reaching full maturation, eventually leading to hypomyelination. Our data demonstrate that SNX27 modulates GPR17 plasma membrane recycling and stability, and that disruption of the SNX27/GPR17 interaction might contribute to pathological oligodendrocyte differentiation defects. GLIA 2016. GLIA 2016;64:1437-1460.

  4. The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function

    Science.gov (United States)

    Locci, Michela; Draghici, Elena; Marangoni, Francesco; Bosticardo, Marita; Catucci, Marco; Aiuti, Alessandro; Cancrini, Caterina; Marodi, Laszlo; Espanol, Teresa; Bredius, Robbert G.M.; Thrasher, Adrian J.; Schulz, Ansgar; Litzman, Jiri; Roncarolo, Maria Grazia; Casorati, Giulia; Dellabona, Paolo

    2009-01-01

    The Wiskott-Aldrich syndrome (WAS) protein (WASp) is a regulator of actin cytoskeleton in hematopoietic cells. Mutations of the WASp gene cause WAS. Although WASp is involved in various immune cell functions, its role in invariant natural killer T (iNKT) cells has never been investigated. Defects of iNKT cells could indeed contribute to several WAS features, such as recurrent infections and high tumor incidence. We found a profound reduction of circulating iNKT cells in WAS patients, directly correlating with the severity of clinical phenotype. To better characterize iNKT cell defect in the absence of WASp, we analyzed was−/− mice. iNKT cell numbers were significantly reduced in the thymus and periphery of was−/− mice as compared with wild-type controls. Moreover analysis of was−/− iNKT cell maturation revealed a complete arrest at the CD44+ NK1.1− intermediate stage. Notably, generation of BM chimeras demonstrated a was−/− iNKT cell-autonomous developmental defect. was−/− iNKT cells were also functionally impaired, as suggested by the reduced secretion of interleukin 4 and interferon γ upon in vivo activation. Altogether, these results demonstrate the relevance of WASp in integrating signals critical for development and functional differentiation of iNKT cells and suggest that defects in these cells may play a role in WAS pathology. PMID:19307326

  5. Metabolic syndrome and C-reactive protein in patients with depressive disorder on antidepressive medication.

    Science.gov (United States)

    Stanojević, Albina; Popović, Irena; Nenadović, Milutin; Ravanić, Dragan; Paunović-Milosavljević, Gordana

    2013-01-01

    Recurrent depression is a psychiatric disorder of which etiology and pathogenesis might be related to immune response. Metabolic Syndrome (MetS) and its components are also strongly associated with elevated inflammatory indicators, as so as the body mass index (BMI) and total cholesterol levels. Objective of this study was to investigate if there was any difference in C-reactive protein (CRP) levels in patients with recurrent depressive disorder, treated with antidepressants, compared to a healthy control group of subjects and if there was an association between increased CRP levels and the presence of MetS in these two groups. Sixty subjects entered the study; of these 35 patients with the diagnosis of recurrent depressive disorder, while the healthy control group included 25 subjects. MetS was defined according to the NCEP ATP III criteria. The cut-off point for CRP was set at > 5 mg/L. There was no statistically significant difference in the prevalence of MetS and CRP values between the studied groups. Waist circumference and total cholesterol levels were significantly higher in the experimental group. Patients that fulfilled the criteria for MetS showed significantly higher values of central obesity and arterial hypertension in the experimental group as well. The elevated CRP levels were associated with increased frequency of MetS in depressed patients. Both CRP levels and metabolic risk profile screening, according to the international criteria, may be beneficial in order to obtain better assessment for depressive long-term medicated patients.

  6. Application of GP5 Protein to Develop Monoclonal Antibody against Porcine Reproductive and Respiratory Syndrome Virus

    Institute of Scientific and Technical Information of China (English)

    Hong Tian; Yan Cheng; Jin-yang Wu; Jian-hui He; You-jun Shang; Xiang-tao Liu

    2011-01-01

    In this study,a panel of monoclonal antibodies (mAbs) against Porcine reproductive and respiratory syndrome virus(PRRSV),named as 8C9 and4B4,were produced by fusing SP2/0 myeloma cells and spleen cells of BALB/c mice immunized with the PRRSV (TCID50=5.5),screened by the indirect ELISA and subjected to several limiting dilutions.mAbs were then identified by biological characterization.Among the two fusion cell strains,8C9 belonged to the IgG1 subclass and 4B4 belonged to the IgG2a subclass.The titers in cell culture supernatant and abdomen liquor reached to 1:104and 1:105,respectively.The specificity test indicated that the two cells had specific reactions for the PRRSV and GP5 protein respectively,and no reaction with Classical swine fever virus (CSFV) or Swine vesicular disease virus (SVDV).The molecular weights of the heavy chain and light chain were about 45.0 kDa and 25.0 kDa,respectively.In neutralization activity tests,the results showed that the prepared mAb 4B4 can protect 50% of cells with no CPE in dilution up to 1:512,but mAB 8C9 has no neutralization activities to PRRSV.

  7. Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells.

    Science.gov (United States)

    Cao, Kan; Graziotto, John J; Blair, Cecilia D; Mazzulli, Joseph R; Erdos, Michael R; Krainc, Dimitri; Collins, Francis S

    2011-06-29

    Hutchinson-Gilford progeria syndrome (HGPS) is a lethal genetic disorder characterized by premature aging. HGPS is most commonly caused by a de novo single-nucleotide substitution in the lamin A/C gene (LMNA) that partially activates a cryptic splice donor site in exon 11, producing an abnormal lamin A protein termed progerin. Accumulation of progerin in dividing cells adversely affects the integrity of the nuclear scaffold and leads to nuclear blebbing in cultured cells. Progerin is also produced in normal cells, increasing in abundance as senescence approaches. Here, we report the effect of rapamycin, a macrolide antibiotic that has been implicated in slowing cellular and organismal aging, on the cellular phenotypes of HGPS fibroblasts. Treatment with rapamycin abolished nuclear blebbing, delayed the onset of cellular senescence, and enhanced the degradation of progerin in HGPS cells. Rapamycin also decreased the formation of insoluble progerin aggregates and induced clearance through autophagic mechanisms in normal fibroblasts. Our findings suggest an additional mechanism for the beneficial effects of rapamycin on longevity and encourage the hypothesis that rapamycin treatment could provide clinical benefit for children with HGPS.

  8. Immunological Features of the Non-Structural Proteins of Porcine Reproductive and Respiratory Syndrome Virus

    Directory of Open Access Journals (Sweden)

    Edgar Rascón-Castelo

    2015-02-01

    Full Text Available Porcine reproductive and respiratory syndrome virus (PRRSV is currently one of the most important viruses affecting the swine industry worldwide. Despite the large number of papers published each year, the participation of non-structural proteins (nsps in the immune response is not completely clear. nsps have been involved in the host innate immune response, specifically, nsp1α/β, nsp2, nsp4 and nsp11 have been associated with the immunomodulation capability of the virus. To date, only participation by nsp1, nsp2, nsp4 and nsp7 in the humoral immune response has been reported, with the role of other nsps being overlooked. Furthermore, nsp1, nsp2, nsp5, nsp7 nsp9, nsp10, nsp11 have been implicated in the induction of IFN-γ and probably in the development of the cell-mediated immune response. This review discusses recent reports involving the participation of nsps in the modulation of the innate immune response and their role in the induction of both the humoral and cellular immune responses.

  9. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes.

    Science.gov (United States)

    Schubert, Julian; Siekierska, Aleksandra; Langlois, Mélanie; May, Patrick; Huneau, Clément; Becker, Felicitas; Muhle, Hiltrud; Suls, Arvid; Lemke, Johannes R; de Kovel, Carolien G F; Thiele, Holger; Konrad, Kathryn; Kawalia, Amit; Toliat, Mohammad R; Sander, Thomas; Rüschendorf, Franz; Caliebe, Almuth; Nagel, Inga; Kohl, Bernard; Kecskés, Angela; Jacmin, Maxime; Hardies, Katia; Weckhuysen, Sarah; Riesch, Erik; Dorn, Thomas; Brilstra, Eva H; Baulac, Stephanie; Møller, Rikke S; Hjalgrim, Helle; Koeleman, Bobby P C; Jurkat-Rott, Karin; Lehman-Horn, Frank; Roach, Jared C; Glusman, Gustavo; Hood, Leroy; Galas, David J; Martin, Benoit; de Witte, Peter A M; Biskup, Saskia; De Jonghe, Peter; Helbig, Ingo; Balling, Rudi; Nürnberg, Peter; Crawford, Alexander D; Esguerra, Camila V; Weber, Yvonne G; Lerche, Holger

    2014-12-01

    Febrile seizures affect 2-4% of all children and have a strong genetic component. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B, that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes.

  10. Cockayne syndrome group B (CSB) protein: at the crossroads of transcriptional networks.

    Science.gov (United States)

    Vélez-Cruz, Renier; Egly, Jean-Marc

    2013-01-01

    Cockayne syndrome (CS) is a rare genetic disorder characterized by a variety of growth and developmental defects, photosensitivity, cachectic dwarfism, hearing loss, skeletal abnormalities, progressive neurological degeneration, and premature aging. CS arises due to mutations in the CSA and CSB genes. Both gene products are required for the transcription-coupled (TC) branch of the nucleotide excision repair (NER) pathway, however, the severe phenotype of CS patients is hard to reconcile with a sole defect in TC-NER. Studies using cells from patients and mouse models have shown that the CSB protein is involved in a variety of cellular pathways and plays a major role in the cellular response to stress. CSB has been shown to regulate processes such as the transcriptional recovery after DNA damage, the p53 transcriptional response, the response to hypoxia, the response to insulin-like growth factor-1 (IGF-1), transactivation of nuclear receptors, transcription of housekeeping genes and the transcription of rDNA. Some of these processes are also affected in combined XP/CS patients. These new advances in the function(s) of CSB shed light onto the etiology of the clinical features observed in CS patients and could potentially open therapeutic avenues for these patients in the future. Moreover, the study of CS could further our knowledge of the aging process.

  11. Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response.

    Science.gov (United States)

    Ciccia, Alberto; Huang, Jen-Wei; Izhar, Lior; Sowa, Mathew E; Harper, J Wade; Elledge, Stephen J

    2014-12-30

    The signal transduction pathway of the DNA damage response (DDR) is activated to maintain genomic integrity following DNA damage. The DDR promotes genomic integrity by regulating a large network of cellular activities that range from DNA replication and repair to transcription, RNA splicing, and metabolism. In this study we define an interaction between the DDR factor NBS1 and TCOF1, a nucleolar protein that regulates ribosomal DNA (rDNA) transcription and is mutated in Treacher Collins syndrome. We show that NBS1 relocalizes to nucleoli after DNA damage in a manner dependent on TCOF1 and on casein kinase II and ATM, which are known to modify TCOF1 by phosphorylation. Moreover, we identify a putative ATM phosphorylation site that is required for NBS1 relocalization to nucleoli in response to DNA damage. Last, we report that TCOF1 promotes cellular resistance to DNA damaging agents. Collectively, our findings identify TCOF1 as a DDR factor that could cooperate with ATM and NBS1 to suppress inappropriate rDNA transcription and maintain genomic integrity after DNA damage.

  12. C-reactive protein level and obesity as cardiovascular risk factors in polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Eda Ülkü Uludağ

    2013-09-01

    Full Text Available Objective: To investigate the role of C-reactive protein(CRP level elevation and obesity for the increased cardiovasculardisease risk in polycystic ovary syndrome(PCOS.Methods: A hundred and nine patients with PCOS and 30age matched healthy volunteers with regular menstrualcycle are involved in the study. PCOS group is furthersubdivided into three subgroups according to the bodymass index (BMI. Subgroups included 54 with BMI30. Blood samplesfor glucose, insulin, uric acid, and CRP were collected inthe morning after overnight fasting (12 hours. Homeostasismodel assessment-insulin resistance (HOMA-IRwas calculated. Results: Fasting blood glucose, insulin,and HOMA-IR was significantly higher in PCOS group(p=0.02, p=0.01 and p=0.02. CRP level was higher insubgroup with BMI>30. High CRP level in PCOS wasfound to be independent from BMI (p30.When compared with the control group high insulin levelwas the only to be statistically significant in obese PCOSpatients (p=0.005. HOMA-IR was higher in PCOS subgroupwith BMI>30 when compared with controls and thePCOS subgroup with BMI<25 (p<0.001, p= 0.003.Conclusion: Obesity, hyperinsulinemia, and high CRPlevels are seemed to be related and potentiating eachother in PCOS. Struggling with obesity is one of the mostimportant issues for preventive medicine.Key words: PCOS, CRP, obesity, cardiovascular risk

  13. Characterisation of transparent exopolymer particles (TEP) produced during algal bloom: A membrane treatment perspective

    KAUST Repository

    Villacorte, Loreen O.

    2013-01-01

    Algal blooms are currently a major concern of the membrane industry as it generates massive concentrations of organic matter (e.g. transparent exopolymer particles [TEP]), which can adversely affect the operation of membrane filtration systems. The goal of this study is to understand the production, composition and membrane rejection of these organic materials using different characterisation techniques. Two common species of bloom-forming freshwater and marine algae were cultivated in batch cultures for 30days and the productions of TEP and other organic matter were monitored at different growth phases. TEP production of the marine diatom, Chaetoceros affinis, produced 6-9 times more TEP than the freshwater blue-green algae, Microcystis. The organic substances produced by both algal species were dominated by biopolymeric substances such as polysaccharides (45-64%) and proteins (2-17%) while the remaining fraction comprises of low molecular weight refractory (humic-like) and/ or biogenic organic substances. MF/UF membranes mainly rejected the biopolymers but not the low molecular weight organic materials. MF membranes (0.1-0.4 lm) rejected 42-56% of biopolymers, while UF membranes (10-100 kDa) rejected 65-95% of these materials. Further analysis of rejected organic materials on the surface of the membranes revealed that polysac-charides and proteins are likely responsible for the fouling of MF/UF systems during an algal bloom situation. © 2013 Desalination Publications.

  14. Serum Heat Shock Protein 70 Concentration in Relation to Polycystic Ovary Syndrome in a Non-Obese Chinese Population

    OpenAIRE

    Hui Gao; Jie Meng; Mengjing Xu; Shun Zhang; Bishwajit Ghose; Jun Liu; Ping Yao; Hong Yan; Di Wang; Liegang Liu

    2013-01-01

    Background Polycystic ovary syndrome (PCOS) represents the most common cause of anovulatory infertility and affects 6-15% of women of reproductive age. However, the underlying etiology is still poorly understood. In this study, we attempted to examine the association between circulating heat shock protein 70 (Hsp70) concentrations and PCOS in a non-obese Chinese population. Methods and Results Human peripheral blood from 52 patients with PCOS and 57 healthy controls, matched for age and BMI, ...

  15. Correlation between the serum level of advanced oxidation protein products and the cognitive function in patients with obstructive sleep apnea hypopnea syndrome

    Institute of Scientific and Technical Information of China (English)

    杨秀红

    2013-01-01

    Objective To observe the change of the cognitive function and the serum level of advanced oxidation protein products(AOPP) in patients with obstructive sleep apnea hypopnea syndrome(OSAHS),and then to investigate

  16. A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen.

    Science.gov (United States)

    Xue, Dahai; Shi, Hong; Smith, James D; Chen, Xinguo; Noe, Dennis A; Cedervall, Tommy; Yang, Derek D; Eynon, Elizabeth; Brash, Douglas E; Kashgarian, Michael; Flavell, Richard A; Wolin, Sandra L

    2003-06-24

    Antibodies against a conserved RNA-binding protein, the Ro 60-kDa autoantigen, occur in 24-60% of all patients with systemic lupus erythematosus. Anti-Ro antibodies are correlated with photosensitivity and cutaneous lesions in these patients and with neonatal lupus, a syndrome in which mothers with anti-Ro antibodies give birth to children with complete congenital heart block and photosensitive skin lesions. In higher eukaryotes, the Ro protein binds small RNAs of unknown function known as Y RNAs. Because the Ro protein also binds misfolded 5S rRNA precursors, it is proposed to function in a quality-control pathway for ribosome biogenesis. Consistent with a role in the recognition or repair of intracellular damage, an orthologue of Ro in the radiation-resistant eubacterium Deinococcus radiodurans contributes to survival of this bacterium after UV irradiation. Here, we show that mice lacking the Ro protein develop an autoimmune syndrome characterized by anti-ribosome antibodies, anti-chromatin antibodies, and glomerulonephritis. Moreover, in one strain background, Ro-/- mice display increased sensitivity to irradiation with UV light. Thus, one function of this major human autoantigen may be to protect against autoantibody development, possibly by sequestering defective ribonucleoproteins from immune surveillance. Furthermore, the finding that mice lacking the Ro protein are photosensitive suggests that loss of Ro function could contribute to the photosensitivity associated with anti-Ro antibodies in humans.

  17. Induction of macrophage chemotaxis by aortic extracts from patients with Marfan syndrome is related to elastin binding protein.

    Directory of Open Access Journals (Sweden)

    Gao Guo

    Full Text Available Marfan syndrome is an autosomal dominantly inherited disorder of connective tissue with prominent skeletal, ocular, and cardiovascular manifestations. Aortic aneurysm and dissection are the major determinants of premature death in untreated patients. In previous work, we showed that extracts of aortic tissues from the mgR mouse model of Marfan syndrome showed increased chemotactic stimulatory activity related to the elastin-binding protein. Aortic samples were collected from 6 patients with Marfan syndrome and 8 with isolated aneurysms of the ascending aorta. Control samples were obtained from 11 organ donors without known vascular or connective tissue diseases. Soluble proteins extracted from the aortic samples of the two patient groups were compared against buffer controls and against the aortic samples from controls with respect to the ability to induce macrophage chemotaxis as measured using a modified Boyden chamber, as well as the reactivity to a monoclonal antibody BA4 against bioactive elastin peptides using ELISA. Samples from Marfan patients displayed a statistically significant increase in chemotactic inductive activity compared to control samples. Additionally, reactivity to BA4 was significantly increased. Similar statistically significant increases were identified for the samples from patients with idiopathic thoracic aortic aneurysm. There was a significant correlation between the chemotactic index and BA4 reactivity, and the increases in chemotactic activity of extracts from Marfan patients could be inhibited by pretreatment with lactose, VGVAPG peptides, or BA4, which indicates the involvement of EBP in mediating the effects. Our results demonstrate that aortic extracts of patients with Marfan syndrome can elicit macrophage chemotaxis, similar to our previous study on aortic extracts of the mgR mouse model of Marfan syndrome (Guo et al., Circulation 2006; 114:1855-62.

  18. Effects of bromocriptine on CSF proteins and amines in patients with empty sella syndrome, acromegaly and prolactin producing pituitary adenomas.

    Science.gov (United States)

    Brismar, K; Sidén, A; Werner, S

    1981-01-01

    The effect of the dopamine agonist bromocriptine (5-40 mg/day) on cerebrospinal fluid proteins and amines was studied in 7 hyperprolactinemic patients, 4 with empty sella syndrome and 3 patients with pituitary adenoma. Small as well as high doses of bromocriptine depressed the endogenously formed dopamine, noradrenalin and adrenalin. Five patients initially exhibited changes consistent with slight to marked blood-cerebrospinal-fluid (CSF) barrier disturbances and 5 abnormal CSF-protein fractions. One CSF-protein fraction (isolelectric points (pI) approximately 5.3 pH-units) became more prominent during bromocriptine treatment. Analyses of his fraction indicated that it represented a transferrin component. It is stated that bromocriptine treatment besides affecting amine and trace metal metabolism also affects protein metabolism.

  19. Harmful Algal Bloom Research in China

    Institute of Scientific and Technical Information of China (English)

    Su Jilan; Zhou Mingjiang

    2001-01-01

    Proliferations of harmful algae in coastal waters, i.e., harmful algal blooms (HABs), popularly known as "red tides," have attracted the concern of governments and scientists worldwide. In recent years, HABs have occurred in China with increasing frequency and scope. These outbreaks have seriously affected the economy along the coast through fish kills, heavy losses in aquaculture, threats to human health, and other effects detrimental to the marine ecosystem. Therefore, it is important to pay special attention to the ecology and oceanography studies related to the outbreak of HABs. Only through the combination of the advancement of such knowledge with the strengthening of the monitoring network can we develop a HAB warning system for the sustainable development of the coastal economy.

  20. Activated protein C in the treatment of acute lung injury and acute respiratory distress syndrome

    NARCIS (Netherlands)

    A.D. Cornet; G.P. van Nieuw Amerongen; A. Beishuizen; M.J. Schultz; A.R.J. Girbes; A.B.J. Groeneveld

    2009-01-01

    Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) frequently necessitate mechanical ventilation in the intensive care unit. The syndromes have a high mortality rate and there is at present no treatment specifically directed at the underlying pathogenesis. Central in

  1. The sequence-specific transcription factor c-Jun targets Cockayne syndrome protein B to regulate transcription and chromatin structure.

    Directory of Open Access Journals (Sweden)

    Robert J Lake

    2014-04-01

    Full Text Available Cockayne syndrome is an inherited premature aging disease associated with numerous developmental and neurological defects, and mutations in the gene encoding the CSB protein account for the majority of Cockayne syndrome cases. Accumulating evidence suggests that CSB functions in transcription regulation, in addition to its roles in DNA repair, and those defects in this transcriptional activity might contribute to the clinical features of Cockayne syndrome. Transcription profiling studies have so far uncovered CSB-dependent effects on gene expression; however, the direct targets of CSB's transcriptional activity remain largely unknown. In this paper, we report the first comprehensive analysis of CSB genomic occupancy during replicative cell growth. We found that CSB occupancy sites display a high correlation to regions with epigenetic features of promoters and enhancers. Furthermore, we found that CSB occupancy is enriched at sites containing the TPA-response element. Consistent with this binding site preference, we show that CSB and the transcription factor c-Jun can be found in the same protein-DNA complex, suggesting that c-Jun can target CSB to specific genomic regions. In support of this notion, we observed decreased CSB occupancy of TPA-response elements when c-Jun levels were diminished. By modulating CSB abundance, we found that CSB can influence the expression of nearby genes and impact nucleosome positioning in the vicinity of its binding site. These results indicate that CSB can be targeted to specific genomic loci by sequence-specific transcription factors to regulate transcription and local chromatin structure. Additionally, comparison of CSB occupancy sites with the MSigDB Pathways database suggests that CSB might function in peroxisome proliferation, EGF receptor transactivation, G protein signaling and NF-κB activation, shedding new light on the possible causes and mechanisms of Cockayne syndrome.

  2. Physical Hydrography and Algal Bloom Transport in Hong Kong Waters

    Institute of Scientific and Technical Information of China (English)

    KUANG Cui-ping; LEE Joseph H.W.

    2005-01-01

    In sub-tropical coastal waters around Hong Kong, algal blooms and red tides are usually first sighted in the Mirs Bay, in the eastern waters of Hong Kong. A calibrated three-dimensional hydrodynamic model for the Pearl River Estuary (Delft3D) has been applied to the study of the physical hydrography of Hong Kong waters and its relationship with algal bloom transport patterns in the dry and wet seasons. The general 3D hydrodynamic circulation and salinity structure in the partially-mixed estuary are presented. Extensive numerical surface drogue tracking experiments are performed for algal blooms that are initiated in the Mirs Bay under different seasonal, wind and tidal conditions. The probability of bloom impact on the Victoria Harbour and nearby urban coastal waters is estimated. The computations show that: I) In the wet season (May~August), algal blooms initiated in the Mirs Bay will move in a clockwise direction out of the bay, and be transported away from Hong Kong due to SW monsoon winds which drive the SW to NE coastal current; ii) In the dry season (November~April), algal blooms initiated in the northeast Mirs Bay will move in an anti-clockwise direction and be carried away into southern waters due to the NE to SW coastal current driven by the NE monsoon winds; the bloom typically flows past the east edge of the Victoria Harbour and nearby waters. Finally, the role of hydrodynamic transport in an important episodic event - the spring 1998 massive red tide - is quantitatively examined. It is shown that the strong NE to E wind during late March to early April, coupled with the diurnal tide at the beginning of April, significantly increased the probability of bloom transport into the Port Shelter and East Lamma Channel, resulting in the massive fish kill. The results provide a basis for risk assessment of harmful algal bloom (HAB) impact on urban coastal waters around the Victoria Habour.

  3. Investigating the presence of predatory bacteria on algal bloom samples using a T6SS gene marker.

    Science.gov (United States)

    Hendricks, J.; Sison-Mangus, M.; Mehic, S.; McMahon, E.

    2015-12-01

    Predation is considered to be a major driving force in evolution and ecology, which has been observed affecting individual organisms, communities, and entire ecosystems. The type VI secretion system (T6SS) is an intermembranal protein complex identified in certain bacteria, which appears to have evolved strictly as a mechanism of predation. The effects of bacteria on phytoplankton physiology are still understudied, however, studies have shown that the interactions between bacteria that inhabit the phycosphere of phytoplankton can possibly result in coevolution of native host and microbiota. It is unclear if bacteria can prey upon other bacteria to gain advantages during periods of high phytoplankton density. Here, we investigate the predatory interactions between bacteria and analyze environmental samples for the presence of predatory bacterial genes in an effort to understand bacteria-bacteria and phytoplankton interactions during algal blooms. DNA were extracted from bacterial samples collected weekly from size-fractionated samples using 3.0 um and 0.2 um membrane filters at the Santa Cruz wharf. PCR amplification and gel visualization for the presence of T6SS gene was carried out on bloom and non-bloom samples. Moreover, we carried out a lab- based experiment to observe bacteria-bacteria interaction that may hint for the presence of predatory behavior between bacterial taxa. We observed what appeared to be a predatory biofilm formation between certain bacterial species. These bacteria, however, did not contain the T6SS genes. On the contrary the T6SS gene was discovered in some of the bloom samples gathered from the Santa Cruz wharf. It is still unclear if the predatory mechanisms facilitate the abundance of certain groups of bacteria that contain the T6SS genes during algal blooms, but our evidence suggest that bacterial predation through T6SS mechanism is present during bloom events.

  4. Seasonal phytoplankton blooms in the North Atlantic linked to the overwintering strategies of copepods

    Directory of Open Access Journals (Sweden)

    Kevin D. Friedland

    2016-04-01

    Full Text Available Abstract The North Atlantic Ocean contains diverse patterns of seasonal phytoplankton blooms with distinct internal dynamics. We analyzed blooms using remotely-sensed chlorophyll a concentration data and change point statistics. The first bloom of the year began during spring at low latitudes and later in summer at higher latitudes. In regions where spring blooms occurred at high frequency (i.e., proportion of years that a bloom was detected, there was a negative correlation between bloom timing and duration, indicating that early blooms last longer. In much of the Northeast Atlantic, bloom development extended over multiple seasons resulting in peak chlorophyll concentrations in summer. Spring bloom start day was found to be positively correlated with a spring phenology index and showed both positive and negative correlations to sea surface temperature and the North Atlantic Oscillation in different regions. Based on the characteristics of spring and summer blooms, the North Atlantic can be classified into two regions: a seasonal bloom region, with a well-defined bloom limited to a single season; and a multi-seasonal bloom region, with blooms extending over multiple seasons. These regions differed in the correlation between bloom start and duration with only the seasonal bloom region showing a significant, negative correlation. We tested the hypothesis that the near-surface springtime distribution of copepods that undergo diapause (Calanus finmarchicus, C. helgolandicus, C. glacialis, and C. hyperboreus may contribute to the contrast in bloom development between the two regions. Peak near-surface spring abundance of the late stages of these Calanoid copepods was generally associated with areas having a well-defined seasonal bloom, implying a link between bloom shape and their abundance. We suggest that either grazing is a factor in shaping the seasonal bloom or bloom shape determines whether a habitat is conducive to diapause, while recognizing

  5. Optical researches for cyanobacteria bloom monitoring in Curonian Lagoon

    Science.gov (United States)

    Shirshin, Evgeny A.; Budylin, Gleb B.; Yakimov, Boris P.; Voloshina, Olga V.; Karabashev, Genrik S.; Evdoshenko, Marina A.; Fadeev, Victor V.

    2016-04-01

    Cyanobacteria bloom is a great ecological problem of Curonian Lagoon and Baltic Sea. The development of novel methods for the on-line control of cyanobacteria concentration and, moreover, for prediction of bloom spreading is of interest for monitoring the state of ecosystem. Here, we report the results of the joint application of hyperspectral measurements and remote sensing of Curonian Lagoon in July 2015 aimed at the assessment of cyanobacteria communities. We show that hyperspectral data allow on-line detection and qualitative estimation of cyanobacteria concentration, while the remote sensing data indicate the possibility of cyanobacteria bloom detection using the spectral features of upwelling irradiation.

  6. Surfactant protein B gene polymorphism in preterm babies with respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    P.P.R. Lyra

    2011-01-01

    Full Text Available The etiology of respiratory distress syndrome (RDS is multifactorial and multigenic. Studies have suggested that polymorphisms and mutations in the surfactant protein B (SP-B gene are associated with the pathogenesis of RDS. The objectives of this study were to determine and compare the frequencies of SP-B gene polymorphisms in preterm babies with and without RDS. We studied 151 neonates: 79 preterm babies without RDS and 72 preterm newborns with RDS. The following four SP-B gene polymorphisms were analyzed: A/C at -18, C/T at 1580, A/G at 9306, and G/C at nucleotide 8714. The polymorphisms were detected by PCR amplification of genomic DNA and genotyping. The genotypes were determined using PCR-based converted restriction fragment length polymorphisms. The control group consisted of 42 (53% girls and 37 (47% boys. Weight ranged from 1170 to 3260 g and mean gestational age (GA was 33.9 weeks (range: 29 to 35 weeks and 6 days. The RDS group consisted of 31 (43% girls and 41 (57% boys. Weight ranged from 614 to 2410 g and mean GA was 32 weeks (range: 26 to 35 weeks. The logistic regression model showed that GA was the variable that most contributed to the occurrence of RDS. The AG genotype of the A/G polymorphism at position 9306 of the SP-B gene was a protective factor in this population (OR = 0.1681; 95%CI = 0.0426-0.6629. We did not detect differences in the frequencies of the other polymorphisms between the two groups of newborns.

  7. C-reactive protein in patients with Guillain Barré syndrome

    Directory of Open Access Journals (Sweden)

    Chetana Vaishnavi

    2014-01-01

    Full Text Available Context: C-reactive protein (CRP is an acute phase reactant, widely used as a biomarker for various infectious and inflammatory conditions. Guillain-Barrι syndrome (GBS is an acute, autoimmune, polyradiculoneuropathy, triggered by infectious agents such as Campylobacter jejuni. GBS is generally precipitated 1-3 weeks following C. jejuni infection which suggests a humoral immunopathogenic mechanism. Aims: Basal CRP levels were estimated in sera of patients with GBS and compared with adequate controls. Settings & Design: The study population was divided into 4 groups: (i GBS group included 45 newly diagnosed GBS patients; (ii Neurological control (NC group comprised of 59 patients with non-paralytic neurological symptoms/disorders; (iii Non-neurological controls (NNC comprised of 43 patients having no neurological symptoms and (iv Healthy controls (HC comprised of 101 healthy subjects. Materials and Methods: CRP was evaluated using slide latex agglutination test (LAT and enzyme linked immunosorbent assay (ELISA. Statistical Analysis: Statistical analysis was done by the Chi-square test. Results: CRP by LAT was positive in 24.4% GBS group, 34% NC group and 44% NNC group. The range of titer in CRP positive samples in the three patient groups (GBS, NC, NNC was at concentration of 0.6 mg/dl to 19.2 mg/dl. Similar results were also obtained by ELISA in the patient groups. None of the HC subjects was positive for detectable levels of CRP. High basal level of CRP was detected in patients with GBS. Conclusion: Autoimmune conditions like GBS can stimulate the production of a high level of inflammation resulting in an increase in the CRP production.

  8. Metabolic syndrome and C-reactive protein in patients with depressive disorder on antidepressive medication

    Directory of Open Access Journals (Sweden)

    Stanojević Albina

    2013-01-01

    Full Text Available Introduction. Recurrent depression is a psychiatric disorder of which etiology and pathogenesis might be related to immune response. Metabolic Syndrome (MetS and its components are also strongly associated with elevated inflammatory indicators, as so as the body mass index (BMI and total cholesterol levels. Objective. Objective of this study was to investigate if there was any difference in C-reactive protein (CRP levels in patients with recurrent depressive disorder, treated with antidepressants, compared to a healthy control group of subjects and if there was an association between increased CRP levels and the presence of MetS in these two groups. Methods. Sixty subjects entered the study; of these 35 patients with the diagnosis of recurrent depressive disorder, while the healthy control group included 25 subjects. MetS was defined according to the NCEP ATP III criteria. The cut-off point for CRP was set at >5 mg /L. Results. There was no statistically significant difference in the prevalence of MetS and CRP values between the studied groups. Waist circumference and total cholesterol levels were significantly higher in the experimental group. Patients that fulfilled the criteria for MetS showed significantly higher values of central obesity and arterial hypertension in the experimental group as well. The elevated CRP levels were associated with increased frequency of MetS in depressed patients. Conclusion. Both CRP levels and metabolic risk profile screening, according to the international criteria, may be beneficial in order to obtain better assessment for depressive long term medicated patients.

  9. Expression of G protein-coupled estrogen receptor in irritable bowel syndrome and its clinical significance.

    Science.gov (United States)

    Qin, Bin; Dong, Lei; Guo, Xiaoyan; Jiang, Jiong; He, Yangxin; Wang, Xiaoyan; Li, Lu; Zhao, Juhui

    2014-01-01

    Estrogen is suggested to participate in pathogenesis of irritable bowel syndrome (IBS), but expression of G protein-coupled estrogen receptor (GPER) in the colon of IBS patients has never been investigated. The aim of this study was to investigate the expression of GPER and classical estrogen receptors in the colon of IBS patients and healthy controls. Colonic biopsies were obtained by endoscopy from patients with IBS (n=46) and healthy subjects (n=13). Expression of GPER, estrogen receptor α (ERα) and estrogen receptor β (ERβ) in mast cells were measured by double-labelling immunofluorescence. Quantification of mRNA expression was performed for GPER, ERα and ERβ by real-time polymerase chain reaction. Differential distribution of GPER, ERα and ERβ were detected in human colonic mucosa. The expression of GPER in the cytoplasm of mast cells and GPER-positive cells was significantly higher in diarrhea-predominant IBS (D-IBS) patients than that in constipation-predominant IBS (C-IBS, Pcolonic mucosa and no difference of immunostaining results for ERα and ERβ was found among these three groups. A positive correlation (r=0.451, P=0.011) between GPER-positive cell counts and abdominal pain severity was observed in D-IBS group. Relative mRNA expression of GPER in D-IBS was also higher than that in C-IBS (P=0.018) and healthy subjects (P=0.011). The present study, for the first time, demonstrated the expression of GPER in human colonic mucosa and its correlation with abdominal pain severity.

  10. Does C-reactive Protein Add Prognostic Value to GRACE Score in Acute Coronary Syndromes?

    Energy Technology Data Exchange (ETDEWEB)

    Correia, Luis Cláudio Lemos, E-mail: lccorreia@terra.com.br; Vasconcelos, Isis; Garcia, Guilherme; Kalil, Felipe; Ferreira, Felipe; Silva, André; Oliveira, Ruan; Carvalhal, Manuela; Freitas, Caio; Noya-Rabelo, Márcia Maria [Escola Bahiana de Medicina e Saúde Pública, Salvador, BA (Brazil); Hospital São Rafael, Salvador, BA (Brazil)

    2014-05-15

    The incremental prognostic value of plasma levels of C-reactive protein (CRP) in relation to GRACE score has not been established in patients with acute coronary syndrome (ACS) with non-ST segment elevation. To test the hypothesis that CRP measurements at admission increases the prognostic value of GRACE score in patients with ACS. A total of 290 subjects, consecutively admitted for ACS, with plasma material obtained upon admission CRP measurement using a high-sensitivity method (nephelometry) were studied. Cardiovascular outcomes during hospitalization were defined by the combination of death, nonfatal myocardial infarction or nonfatal refractory angina. The incidence of cardiovascular events during hospitalization was 15% (18 deaths, 11 myocardial infarctions, 13 angina episodes) with CRP showing C-statistics of 0.60 (95% CI = 0.51-0.70, p = 0.034) in predicting these outcomes. After adjustment for the GRACE score, elevated CRP (defined as the best cutoff point) tended to be associated with hospital events (OR = 1.89, 95% CI = 0.92 to 3.88, p = 0.08). However, the addition of the variable elevated CRP in the GRACE model did not result in significant increase in C-statistics, which ranged from 0.705 to 0.718 (p = 0.46). Similarly, there was no significant reclassification of risk with the addition of CRP in the predictor model (net reclassification = 5.7 %, p = 0.15). Although CRP is associated with hospital outcomes, this inflammatory marker does not increase the prognostic value of the GRACE score.

  11. System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability

    DEFF Research Database (Denmark)

    Xiao, Zhenyu; Chang, Jer-Gung; Hendriks, Ivo A;

    2015-01-01

    . Following statistical analysis on five biological replicates, a total of 566 SUMO-2 targets were identified. After 2 hours of Hydroxyurea treatment, 10 proteins were up-regulated for SUMOylation and 2 proteins were down-regulated for SUMOylation, whereas after 24 hours, 35 proteins were up......-regulated for SUMOylation and 13 proteins were down-regulated for SUMOylation. A site-specific approach was used to map over 1,000 SUMO-2 acceptor lysines in target proteins. The methodology is generic and is widely applicable in the ubiquitin field. A large subset of these identified proteins function in one network...... that consists of interacting replication factors, transcriptional regulators, DNA damage response factors including MDC1, ATR-interacting protein ATRIP, the Bloom syndrome protein and the BLM-binding partner RMI1, the crossover junction endonuclease EME1, BRCA1 and CHAF1A. Furthermore, centromeric proteins...

  12. The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation.

    Science.gov (United States)

    Dawe, Helen R; Smith, Ursula M; Cullinane, Andrew R; Gerrelli, Dianne; Cox, Phillip; Badano, Jose L; Blair-Reid, Sarah; Sriram, Nisha; Katsanis, Nicholas; Attie-Bitach, Tania; Afford, Simon C; Copp, Andrew J; Kelly, Deirdre A; Gull, Keith; Johnson, Colin A

    2007-01-15

    Meckel-Gruber syndrome (MKS) is an autosomal recessive lethal malformation syndrome characterized by renal cystic dysplasia, central nervous system malformations (typically, posterior occipital encephalocele), and hepatic developmental defects. Two MKS genes, MKS1 and MKS3, have been identified recently. The present study describes the cellular, sub-cellular and functional characterization of the novel proteins, MKS1 and meckelin, encoded by these genes. In situ hybridization studies for MKS3 in early human embryos showed transcript localizations in agreement with the tissue phenotype of MKS patients. Both MKS proteins predominantly localized to epithelial cells, including proximal renal tubules and biliary epithelial cells. MKS1 localized to basal bodies, while meckelin localized both to the primary cilium and to the plasma membrane in ciliated cell-lines and primary cells. Meckelin protein with the Q376P missense mutation was unable to localize at the cell membrane. siRNA-mediated reduction of Mks1 and Mks3 expression in a ciliated epithelial cell-line blocked centriole migration to the apical membrane and consequent formation of the primary cilium. Co-immunoprecipitation experiments show that wild-type meckelin and MKS1 interact and, in three-dimensional tissue culture assays, epithelial branching morphogenesis was severely impaired. These results suggest that MKS proteins mediate a fundamental developmental stage of ciliary formation and epithelial morphogenesis.

  13. Presence of microcystin during events of algal blooms in Araruama Lagoon

    Directory of Open Access Journals (Sweden)

    Manildo Marcião de Oliveira

    2012-04-01

    Full Text Available Algal blooms are phenomena produced by anthropogenic activities, despite the possible natural causes. In Araruama Lagoon, blooms occurred in 2005 and in subsequent years, causing profound changes in phytoplankton communities. These episodes triggered events of extensive fish mortality associated with low levels of dissolved oxygen. Another adverse effect associated with blooms is the production of harmful toxins such as phycotoxins produced by eukaryotic microalgae and cyanotoxins produced by cyanobacteria. Samples of fish (mullet and menhaden and seston showed levels of microcystin by enzyme-linked immunosorbent assay (ELISA, also a seston sample (São Pedro d'Aldeia on 08/22/2007, in a period not related to fish mortality, showed cells which contained genes encoding microcystin synthetase, an enzyme responsible for the synthesis of microcystin. The succession of microalgae with the concomitant presence of potentially toxic cyanobacteria draws attention to the risk of chronic exposure by the population that uses fish as their main protein source.

  14. A Splice Variant of Bardet-Biedl Syndrome 5 (BBS5 Protein that Is Selectively Expressed in Retina.

    Directory of Open Access Journals (Sweden)

    Susan N Bolch

    Full Text Available Bardet-Biedl syndrome is a complex ciliopathy that usually manifests with some form of retinal degeneration, amongst other ciliary-related deficiencies. One of the genetic causes of this syndrome results from a defect in Bardet-Biedl Syndrome 5 (BBS5 protein. BBS5 is one component of the BBSome, a complex of proteins that regulates the protein composition in cilia. In this study, we identify a smaller molecular mass form of BBS5 as a variant formed by alternative splicing and show that expression of this splice variant is restricted to the retina.Reverse transcription PCR from RNA was used to isolate and identify potential alternative transcripts of Bbs5. A peptide unique to the C-terminus of the BBS5 splice variant was synthesized and used to prepare antibodies that selectively recognized the BBS5 splice variant. These antibodies were used on immunoblots of tissue extracts to determine the extent of expression of the alternative transcript and on tissue slices to determine the localization of expressed protein. Pull-down of fluorescently labeled arrestin1 by immunoprecipitation of the BBS5 splice variant was performed to assess functional interaction between the two proteins.PCR from mouse retinal cDNA using Bbs5-specific primers amplified a unique cDNA that was shown to be a splice variant of BBS5 resulting from the use of cryptic splicing sites in Intron 7. The resulting transcript codes for a truncated form of the BBS5 protein with a unique 24 amino acid C-terminus, and predicted 26.5 kD molecular mass. PCR screening of RNA isolated from various ciliated tissues and immunoblots of protein extracts from these same tissues showed that this splice variant was expressed in retina, but not brain, heart, kidney, or testes. Quantitative PCR showed that the splice variant transcript is 8.9-fold (+/- 1.1-fold less abundant than the full-length transcript. In the retina, the splice variant of BBS5 appears to be most abundant in the connecting cilium

  15. Protein profiling in the gut of Penaeus monodon gavaged with oral WSSV-vaccines and live white spot syndrome virus.

    Science.gov (United States)

    Kulkarni, Amod D; Kiron, Viswanath; Rombout, Jan H W M; Brinchmann, Monica F; Fernandes, Jorge M O; Sudheer, Naduvilamuriparampu S; Singh, Bright I S

    2014-07-01

    White spot syndrome virus (WSSV) is a pathogen that causes considerable mortality of the farmed shrimp, Penaeus monodon. Candidate 'vaccines', WSSV envelope protein VP28 and formalin-inactivated WSSV, can provide short-lived protection against the virus. In this study, P. monodon was orally intubated with the aforementioned vaccine candidates, and protein expression in the gut of immunised shrimps was profiled. The alterations in protein profiles in shrimps infected orally with live-WSSV were also examined. Seventeen of the identified proteins in the vaccine and WSSV-intubated shrimps varied significantly compared to those in the control shrimps. These proteins, classified under exoskeletal, cytoskeletal, immune-related, intracellular organelle part, intracellular calcium-binding or energy metabolism, are thought to directly or indirectly affect shrimp's immunity. The changes in the expression levels of crustacyanin, serine proteases, myosin light chain, and ER protein 57 observed in orally vaccinated shrimp may probably be linked to immunoprotective responses. On the other hand, altered expression of proteins linked to exoskeleton, calcium regulation and energy metabolism in WSSV-intubated shrimps is likely to symbolise disturbances in calcium homeostasis and energy metabolism.

  16. Algal bloom response and risk management: On-site response tools.

    Science.gov (United States)

    Watson, Susan B; Zastepa, Arthur; Boyer, Gregory L; Matthews, Eric

    2017-02-13

    Harmful algal blooms caused by cyanobacteria can present a risk to the safety of drinking- and recreational waters and beachfronts through the production of toxins, particularly microcystin, which are highly resilient to degradation. These blooms are difficult to predict, vary in appearance and toxicity, and can show significant spatial heterogeneity: wind- and current-borne scums can produce an order of magnitude range in toxin levels along shorelines. The growing demand for reliable, cost-effective and rapid methods to detect toxins in bloom material and reduce the risk of public exposure cannot be met by most analytical lab turnaround times. Commercial microcystin test kits are now available, but few have been rigorously field-tested or incorporated into monitoring programmes. Working with a local health agency, we evaluated two kits with different operative ranges of detection, applied to samples covering a wide range of water quality, sample matrices, and bloom composition. We compared their performance against lab analyses using Enzyme-Linked Immunosorbent and Protein Phosphatase Inhibition assays. Both kits could resolve samples with high (<10 μg/L microcystin equivalents (MCequiv)) and low/no toxins, but failed to reliably detect toxin levels between 1 and 5 μg/L, at which threshold there were few false negatives (8%) but ∼ one third of the samples (32%) yielded false positives. We conclude that these kits are potentially useful for screening and informed risk management decisions e.g. on beach closures, but should be followed up with more rigorous tests where needed. We describe how, based on these results, the kits have been successfully incorporated into the routine municipal beach monitoring and advisory programme by the Hamilton Public Health Services (Ontario).

  17. Nonstructural carbohydrates and return bloom potential differ among cranberry cultivars

    Science.gov (United States)

    explain low fruit set and biennial bearing tendencies of cranberry (Vaccinium macrocarpon). Yet, comparisons of nonstructural carbohydrate concentrations during critical phenological stages across cultivars that differ in biennial bearing tendencies and return bloom potential are lacking, particular...

  18. Algal blooms: an emerging threat to seawater reverse osmosis desalination

    KAUST Repository

    Villacorte, Loreen O.

    2014-08-04

    Seawater reverse osmosis (SWRO) desalination technology has been rapidly growing in terms of installed capacity and global application over the last decade. An emerging threat to SWRO application is the seasonal proliferation of microscopic algae in seawater known as algal blooms. Such blooms have caused operational problems in SWRO plants due to clogging and poor effluent quality of the pre-treatment system which eventually forced the shutdown of various desalination plants to avoid irreversible fouling of downstream SWRO membranes. This article summarizes the current state of SWRO technology and the emerging threat of algal blooms to its application. It also highlights the importance of studying the algal bloom phenomena in the perspective of seawater desalination, so proper mitigation and preventive strategies can be developed in the near future. © 2014 © 2014 Balaban Desalination Publications. All rights reserved.

  19. Lyngbya majuscula Blooms in an Enclosed Marine Environment

    Directory of Open Access Journals (Sweden)

    Chin Soon Lionel Ng

    2012-06-01

    Full Text Available Cyanobacterial blooms are a cause of concern because of their potential impacts on the marine environment. In Sentosa Cove, Singapore, Lyngbya majuscula blooms appeared regularly in the highly enclosed boat canals traversing the seafront residential development. This study investigated whether sediments resuspended by physical disturbance liberated nutrients that contribute to the blooms. Sediment resuspension events were mimicked in containers of sediment collected from the canals. Lyngbya majuscula that were incubated in containers with resuspended sediment attained greater biomass than those in filtered seawater only. Levels of iron, phosphates and nitrites in seawater with resuspended sediments were significantly higher than in those without. The results indicate that recurrent L. majuscula blooms in Sentosa Cove could be attributed to nutrient loading from sediment resuspension.

  20. Spatial analysis of freshwater lake cyanobacteria blooms, 2008-2011

    Science.gov (United States)

    Background/Question/Methods Cyanobacteria and associated harmful algal blooms cause significant social, economic, and environmental impacts. Cyanobacteria synthesize hepatotoxins, neurotoxins, and dermatotoxins, affecting the health of humans and other species. The Cyanobacteria ...

  1. Cerebrospinal fluid tau and phosphorylated tau protein are elevated in corticobasal syndrome

    NARCIS (Netherlands)

    Aerts, M.B.; Esselink, R.A.J.; Bloem, B.R.; Verbeek, M.M.

    2011-01-01

    Differentiating corticobasal syndrome (CBS) from progressive supranuclear palsy (PSP) and idiopathic Parkinson's disease (PD) can be difficult. To investigate the additional value of cerebrospinal fluid (CSF) biomarkers in the diagnostic differentiation of parkinsonism, we analyzed the CSF concentra

  2. Mutations of the CEP290 gene encoding a centrosomal protein cause Meckel-Gruber syndrome.

    NARCIS (Netherlands)

    Frank, V.; Hollander, A.I. den; Bruchle, N.O.; Zonneveld, M.N.; Nurnberg, G.; Becker, C.; Bois, G. Du; Kendziorra, H.; Roosing, S.; Senderek, J.; Nurnberg, P.; Cremers, F.P.M.; Zerres, K.; Bergmann, C.

    2008-01-01

    Meckel-Gruber syndrome (MKS) is an autosomal recessive, lethal multisystemic disorder characterized by meningooccipital encephalocele, cystic kidney dysplasia, hepatobiliary ductal plate malformation, and postaxial polydactyly. Recently, genes for MKS1 and MKS3 were identified, putting MKS on the

  3. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage

    DEFF Research Database (Denmark)

    Stewart, Grant S.; Panier, Stephanie; Townsend, Kelly

    2009-01-01

    for such disorders is Ataxia-Telangiectasia caused by biallelic mutation in ATM, a central component of the DNA damage response. Here, we report that the ubiquitin ligase RNF168 is mutated in the RIDDLE syndrome, a recently discovered immunodeficiency and radiosensitivity disorder. We show that RNF168 is recruited...... the accumulation of 53BP1 and BRCA1 to DNA lesions, and their loss is the likely cause of the cellular and developmental phenotypes associated with RIDDLE syndrome....

  4. Pulmonary Thromboembolism in Klinefelter%u2019s Syndrome Patient with Deficient of Protein C

    OpenAIRE

    Mehmet Yigit

    2013-01-01

    Klinefelter syndrome (KS) is a common genetic disorder caused by one or more supernumerary X chromosomes. KS poses an increased risk for venous thromboembolic events such as deep venous thrombosis and pulmonary embolism. Klinefelter syndrome is prone to hypercoagulability due to hormonal imbalance and one or more inherited thrombophilic factors. Therefore, patients with KS having a medical history of venous thromboembolism require chest computed tomographic (CT) images and oral anticoagulatio...

  5. Two-Dimensional Differential Gel Electrophoresis to Identify Protein Biomarkers in Amniotic Fluid of Edwards Syndrome (Trisomy 18 Pregnancies.

    Directory of Open Access Journals (Sweden)

    Te-Yao Hsu

    Full Text Available Edwards syndrome (ES is a severe chromosomal abnormality with a prevalence of about 0.8 in 10,000 infants born alive. The aims of this study were to identify candidate proteins associated with ES pregnancies from amniotic fluid supernatant (AFS using proteomics, and to explore the role of biological networks in the pathophysiology of ES.AFS from six second trimester pregnancies with ES fetuses and six normal cases were included in this study. Fluorescence-based two-dimensional difference gel electrophoresis (2D-DIGE and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS were used for comparative proteomic analysis. The identified proteins were further validated by Western blotting and the role of biological networks was analyzed.Twelve protein spots were differentially expressed by more than 1.5-fold in the AFS of the ES pregnancies. MALDI-TOF/MS identified one up-regulated protein: apolipoprotein A1 (ApoA1, and four under-regulated proteins: vitamin D binding protein (VDBP, alpha-1-antitrypsin (A1AT, insulin-like growth factor-binding protein 1 (IGFBP-1, and transthyretin (TTR. Western blot and densitometric analysis of ApoA1, A1AT, IGFBP-1, and TTR confirmed the alteration of these proteins in the amniotic fluid samples. Biological network analysis revealed that the proteins of the ES AFS were involved mainly in lipid and hormone metabolism, immune response, and cardiovascular disease.These five proteins may be involved in the pathogenesis of ES. Further studies are needed to explore.

  6. Harmful algal bloom smart device application: using image analysis and machine learning techniques for early classification of harmful algal blooms (SETAC presentation)

    Science.gov (United States)

    Reports of toxic cyanobacterial blooms, also known as Harmful Algal Blooms (HABS) have increased drastically in recent years. HABS impact human health from causing mild allergies to liver damage and death. The Ecological Stewardship Institute (ESI) at Northern Kentucky Universi...

  7. Harmful algal bloom smart device application: using image analysis and machine learning techniques for early classification of harmful algal blooms (SETAC presentation)

    Science.gov (United States)

    Reports of toxic cyanobacterial blooms, also known as Harmful Algal Blooms (HABS) have increased drastically in recent years. HABS impact human health from causing mild allergies to liver damage and death. The Ecological Stewardship Institute (ESI) at Northern Kentucky Universi...

  8. Algal Bloom in Aquatic Ecosystems-an Overview

    OpenAIRE

    M. Ghorbani; S.A. Mirbagheri; A. H. Hasani; S. M. Monavari; J.Nouri

    2014-01-01

    Algae play an important role in all aquatic ecosystems by providing all living organisms of water bodies with preliminary nutrients and energy required. However, abnormal and excessive algal growth so-called algal bloom would be detrimental as much. Given the importance of algae in aquatic environment as well as their sensitivity to environmental changes, algal measurements are of key components of water quality monitoring programs. The algal blooms could include a variety of adverse impacts...

  9. Fat bloom on chocolate confectionery systems - From core to surface

    OpenAIRE

    Dahlenborg, Hanna

    2014-01-01

    Abstract Fat bloom on chocolate is a major problem for the confectionery industry since the unappetising appearance and negative sensory effects lead to rejection by customers. The presence of fat bloom on chocolate confectionery systems is usually connected to migration of liquid fat due to the difference in composition between filling triacylglycerols (TAGs) and cocoa butter TAGs. The filling TAGs migrate into the chocolate shell where they can dissolve cocoa butter crystals. Consequ...

  10. Meta-analysis: a functional polymorphism in the gene encoding for activity of the serotonin transporter protein is not associated with the irritable bowel syndrome.

    NARCIS (Netherlands)

    Kerkhoven, L.A.S. van; Laheij, R.J.F.; Jansen, J.B.M.J.

    2007-01-01

    BACKGROUND: Serotonin is associated with symptoms of the irritable bowel syndrome, its action is terminated by the serotonin transporter protein. AIM: To assess the association between a functional polymorphism in the gene encoding for activity of the serotonin transporter protein and the irritable

  11. Sarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression.

    Science.gov (United States)

    Zatyka, Malgorzata; Da Silva Xavier, Gabriela; Bellomo, Elisa A; Leadbeater, Wendy; Astuti, Dewi; Smith, Joel; Michelangeli, Frank; Rutter, Guy A; Barrett, Timothy G

    2015-02-01

    Wolfram syndrome is an autosomal recessive disorder characterized by neurodegeneration and diabetes mellitus. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER)-resident transmembrane protein that is involved in the regulation of the unfolded protein response (UPR), intracellular ion homeostasis, cyclic adenosine monophosphate production and regulation of insulin biosynthesis and secretion. In this study, single cell Ca(2+) imaging with fura-2 and direct measurements of free cytosolic ATP concentration ([ATP]CYT) with adenovirally expressed luciferase confirmed a reduced and delayed rise in cytosolic free Ca(2+) concentration ([Ca(2+)]CYT), and additionally, diminished [ATP]CYT rises in response to elevated glucose concentrations in WFS1-depleted MIN6 cells. We also observed that sarco(endo)plasmic reticulum ATPase (SERCA) expression was elevated in several WFS1-depleted cell models and primary islets. We demonstrated a novel interaction between WFS1 and SERCA by co-immunoprecipitation in Cos7 cells and with endogenous proteins in human neuroblastoma cells. This interaction was reduced when cells were treated with the ER stress inducer dithiothreitol. Treatment of WFS1-depleted neuroblastoma cells with the proteasome inhibitor MG132 resulted in reduced accumulation of SERCA levels compared with wild-type cells. Together these results reveal a role for WFS1 in the negative regulation of SERCA and provide further insights into the function of WFS1 in calcium homeostasis.

  12. Mathematical model of heat transfer for bloom continuous casting

    Institute of Scientific and Technical Information of China (English)

    Qing Liu; Liangzhou Wang; Liqiang Zhang; Liguo Cao; Xiuzhong Ding; Mei Liang; Yongge Qi

    2008-01-01

    A mathematical model for heat transfer during solidification in continuous casting of automobile steel, was established on researching under the influence of the solidifying process of bloom quality of CCM in the EAF steelmaking shop, at Shijiazhuang Iron and Steel Co. Ltd. Several steel grades were chosen to research, such as, 40Cr and 42CrMo. According to the results of the high temperature mechanical property tests of blooms, the respective temperature curves for controlling the solidification of differem steels were acquired, and a simulating software was developed. The model was verified using two methods, which were bloom pin-shooting and surface strand temperature measuring experiments. The model provided references for research on the solidifying proc-ess and optimization of a secondary cooling system for automobile steel. Moreover, it was already applied to real production. The calculated temperature distribution and solidification trend of blooms had offered a reliable theory for optimizing the solidifying process of blooms, increasing withdrawal speed, and improving bloom quality. Meanwhile, a new secondary cooling system was designed to optimize a secondary cooling water distribution, including choice and arrangements of nozzles, calculation of cooling water quantity, and so on.

  13. Effects of fertilizers used in agricultural fields on algal blooms

    Science.gov (United States)

    Chakraborty, Subhendu; Tiwari, P. K.; Sasmal, S. K.; Misra, A. K.; Chattopadhyay, Joydev

    2017-06-01

    The increasing occurrence of algal blooms and their negative ecological impacts have led to intensified monitoring activities. This needs the proper identification of the most responsible factor/factors for the bloom formation. However, in natural systems, algal blooms result from a combination of factors and from observation it is difficult to identify the most important one. In the present paper, using a mathematical model we compare the effects of three human induced factors (fertilizer input in agricultural field, eutrophication due to other sources than fertilizers, and overfishing) on the bloom dynamics and DO level. By applying a sophisticated sensitivity analysis technique, we found that the increasing use of fertilizers in agricultural field causes more rapid algal growth and decreases DO level much faster than eutrophication from other sources and overfishing. We also look at the mechanisms how fertilizer input rate affects the algal bloom dynamics and DO level. The model can be helpful for the policy makers in determining the influential factors responsible for the bloom formation.

  14. Identification of genetically and oceanographically distinct blooms of jellyfish.

    Science.gov (United States)

    Lee, Patricia L M; Dawson, Michael N; Neill, Simon P; Robins, Peter E; Houghton, Jonathan D R; Doyle, Thomas K; Hays, Graeme C

    2013-03-06

    Reports of nuisance jellyfish blooms have increased worldwide during the last half-century, but the possible causes remain unclear. A persistent difficulty lies in identifying whether blooms occur owing to local or regional processes. This issue can be resolved, in part, by establishing the geographical scales of connectivity among locations, which may be addressed using genetic analyses and oceanographic modelling. We used landscape genetics and Lagrangian modelling of oceanographic dispersal to explore patterns of connectivity in the scyphozoan jellyfish Rhizostoma octopus, which occurs en masse at locations in the Irish Sea and northeastern Atlantic. We found significant genetic structure distinguishing three populations, with both consistencies and inconsistencies with prevailing physical oceanographic patterns. Our analyses identify locations where blooms occur in apparently geographically isolated populations, locations where blooms may be the source or result of migrants, and a location where blooms do not occur consistently and jellyfish are mostly immigrant. Our interdisciplinary approach thus provides a means to ascertain the geographical origins of jellyfish in outbreaks, which may have wide utility as increased international efforts investigate jellyfish blooms.

  15. Competing phytoplankton undermines allelopathy of a bloom-forming dinoflagellate.

    Science.gov (United States)

    Prince, Emily K; Myers, Tracey L; Naar, Jerome; Kubanek, Julia

    2008-12-07

    Biotic interactions in the plankton can be both complex and dynamic. Competition among phytoplankton is often chemically mediated, but no studies have considered whether allelopathic compounds are modified by biotic interactions. Here, we show that compounds exuded during Karenia brevis blooms were allelopathic to the cosmopolitan diatom Skeletonema costatum, but that bloom allelopathy varied dramatically among collections and years. We investigated several possible causes of this variability and found that neither bloom density nor concentrations of water-borne brevetoxins correlated with allelopathic potency. However, when we directly tested whether the presence of competing phytoplankton influenced bloom allelopathy, we found that S. costatum reduced the growth-inhibiting effects of bloom exudates, suggesting that S. costatum has a mechanism for undermining K. brevis allelopathy. Additional laboratory experiments indicated that inducible changes to K. brevis allelopathy were restricted to two diatoms among five sensitive phytoplankton species, whereas five other species were constitutively resistant to K. brevis allelopathy. Our results suggest that competitors differ in their responses to phytoplankton allelopathy, with S. costatum exhibiting a previously undescribed method of resistance that may influence community structure and alter bloom dynamics.

  16. Lacrimal proline rich 4 (LPRR4 protein in the tear fluid is a potential biomarker of dry eye syndrome.

    Directory of Open Access Journals (Sweden)

    Saijyothi Venkata Aluru

    Full Text Available Dry eye syndrome (DES is a complex, multifactorial, immune-associated disorder of the tear and ocular surface. DES with a high prevalence world over needs identification of potential biomarkers so as to understand not only the disease mechanism but also to identify drug targets. In this study we looked for differentially expressed proteins in tear samples of DES to arrive at characteristic biomarkers. As part of a prospective case-control study, tear specimen were collected using Schirmer strips from 129 dry eye cases and 73 age matched controls. 2D electrophoresis (2DE and Differential gel electrophoresis (DIGE was done to identify differentially expressed proteins. One of the differentially expressed protein in DES is lacrimal proline rich 4 protein (LPRR4. LPRR4 protein expression was quantified by enzyme immune sorbent assay (ELISA. LPRR4 was down regulated significantly in all types of dry eye cases, correlating with the disease severity as measured by clinical investigations. Further characterization of the protein is required to assess its therapeutic potential in DES.

  17. Recombinant S-layer proteins of Lactobacillus brevis mediating antibody adhesion to calf intestine alleviated neonatal diarrhea syndrome.

    Science.gov (United States)

    Khang, Yong-Ho; Park, Hee-Young; Jeong, Yoo-Seok; Kim, Jung-Ae; Kim, Young-Hwan

    2009-05-01

    A chimeric gene encoding enhanced green fluorescent protein (EGFP) and a S-layer protein from Lactobacillus brevis KCTC3102, and/or two copies of the Fc-binding Z-domain, a synthetic analog of the B-domain of protein A, was constructed and expressed in Escherichia coli BL21(DE3). The S-layer fusion proteins produced in a 500-l fermentor were likely to be stable in the range of pH 5 to 8 and 0 degree to 40 degrees . Their adhesive property enabled an easy and rapid immobilization of enzymes or antibodies on solid materials such as plastics, glass, sol-gel films, and intestinal epithelial cells. Owing to their affinity towards intestinal cells and immunoglobulin G, the Slayer fusion proteins enabled the adhesion of antibodies to human epithelial cells. In addition, feeding a mixture of the S-layer fusion proteins and antibodies against neonatal calf diarrhea (coronavirus, rotavirus, Escherichia coli, and Salmonella typhimurium) to Hanwoo calves resulted in 100% prevention of neonatal calf diarrhea syndrome (p<0.01),whereas feeding antibodies only resulted in 56% prevention.

  18. Purifying selection in porcine reproductive and respiratory syndrome virus ORF5a protein influences variation in envelope glycoprotein 5 glycosylation.

    Science.gov (United States)

    Robinson, Sally R; Abrahante, Juan E; Johnson, Craig R; Murtaugh, Michael P

    2013-12-01

    Porcine reproductive and respiratory syndrome virus ORF5a protein is encoded in an alternate open reading frame upstream of the major envelope glycoprotein (GP5) in subgenomic mRNA5. Bioinformatic analysis of 3466 type 2 PRRSV sequences showed that the two proteins have co-evolved through a fine balance of purifying codon usage to maintain a conserved RQ-rich motif in ORF5a protein, while eliciting a variable N-linked glycosylation motif in the alternative GP5 reading frame. Conservation of the ORF5a protein RQ-motif also explains an anomalous uracil desert in GP5 hypervariable glycosylation region. The N-terminus of the mature GP5 protein was confirmed to start with amino acid 32, the hypervariable region of the ectodomain. Since GP5 glycosylation variability is assumed to result from immunological selection against neutralizing antibodies, these findings show that an alternative possibility unrelated to immunological selection not only exists, but provides a foundation for investigating previously unsuspected aspects of PRRSV biology. Understanding functional consequences of subtle nucleotide sequence modifications in the region responsible for critical function in ORF5a protein and GP5 glycosylation is essential for rational design of new vaccines against PRRS. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Identification and Characterization of Nuclear Localization Signals within the Nucleocapsid Protein VP15 of White Spot Syndrome Virus

    Institute of Scientific and Technical Information of China (English)

    Li-juan LI; Hua-jun ZHANG; Cong ZHANG; Zheng-li SHI

    2009-01-01

    The nucleocapsid protein VP15 of white spot syndrome virus (WSSV) is a basic DNA-binding protein. Three canonical bipartite nuclear localization signals (NLSs), called NLS1 (aa 11-27), NLS2 (aa 33-49) and NLS3 (44-60), have been detected in this protein, using the ScanProsite computer program. To determine the nuclear localization sequence of VP15, the full-length open reading frame, or the sequence of one of the three NLSs, was fused to the green fluorescent protein (GFP) gene, and transiently expressed in insect Sf9 cells. Transfection with full-length VP15 resulted in GFP fluorescence being distributed exclusively in the nucleus. NLS 1 alone could also direct GFP to the nucleus, but less efficiently. Neither of the other two NLSs (NLS2 and 3) was functional when expressed alone, but exhibited similar activity to NLS1 when they were expressed as a fusion peptide. Furthermore, a mutated VP15, in which the two basic amino acids (11RR12) of NLSI were changed to two alanines (11AA12), caused GFP to be localized only in the cytoplasm of Sf9 cells. These results demonstrated that VP15, as a nuclear localization protein, needs cooperation between its three NLSs, and that the two residues (11RR12) of NLS1 play a key role in transporting the protein to the nucleus.

  20. Harmful algal bloom smart device application: using image analysis and machine learning techniques for early classification of harmful algal blooms

    Science.gov (United States)

    The Ecological Stewardship Institute at Northern Kentucky University and the U.S. Environmental Protection Agency are collaborating to optimize a harmful algal bloom detection algorithm that estimates the presence and count of cyanobacteria in freshwater systems by image analysis...

  1. Harmful algal bloom smart device application: using image analysis and machine learning techniques for early classification of harmful algal blooms

    Science.gov (United States)

    The Ecological Stewardship Institute at Northern Kentucky University and the U.S. Environmental Protection Agency are collaborating to optimize a harmful algal bloom detection algorithm that estimates the presence and count of cyanobacteria in freshwater systems by image analysis...

  2. C-reactive protein in antiphospholipid syndrome: relationship with cardiovascular pathology

    Directory of Open Access Journals (Sweden)

    N V Seredavkina

    2009-01-01

    Full Text Available Objective. To assess relationship of high sensitivity C reactive protein (hsCRP level in pts with antiphospholipid syndrome (APS with clinico-laboratory features and cardiovascular pathology. Material and methods. 206 pts were included. 58 from them had primary APS (PAPS, 72 –systemic lupus erythematosus (SLE with APS and 76 – SLE. 29 from 76 pts of the latter group were positive on anticardiolipin antibodies (ACA – SLE with antiphospholipid antibodies (APhL and 47 – low positive or negative on ACA – SLE without APhL. 72 persons without autoimmune diseases were included into control group. CRP (with high sensitivity immuno-nephelometric assay, APhL (with solid phase immuno-enzyme assay, plasma lipids were evaluated, sonography with measurement of intima-media complex (IMC thickness of common carotid arteries, carotid artery bulbs and internal carotid arteries, electrocardiography (ECG, echocardiography (EchoCG, Holter ECG monitoring were performed. Results. HsCRP serum level in pts was significantly higher than in control: 2,55 [0,71; 7,04] mg/l (varied from 0,15 to 39,85 vs 0,68 [0,26; 1,97] mg/l (varied from 0,1 to 9,61, p<0,001. Most high hsCRP concentration was found in SLE with APS (p=0,02. HsCRP level in pts with PAPS with history of combined or isolated arterial thrombosis was significantly higher than in pts with SLE and APS having the same localization of thrombosis. HsCRP concentration less than 3 mg/l correlated with duration of postthrombotic period in pts with PAPS. HsCRP level also correlated with triglyceride concentration, body mass index, summated coronary risk and magistral arteries IMC thickness. Conclusion. HsCRP elevation in pts with APS was associated with development of combined and arterial thrombosis as well as with traditional risk factors of atherosclerosis.

  3. Spring blooms in the Baltic Sea have weakened but lengthened from 2000 to 2014

    Science.gov (United States)

    Groetsch, Philipp M. M.; Simis, Stefan G. H.; Eleveld, Marieke A.; Peters, Steef W. M.

    2016-09-01

    Phytoplankton spring bloom phenology was derived from a 15-year time series (2000-2014) of ship-of-opportunity chlorophyll a fluorescence observations collected in the Baltic Sea through the Alg@line network. Decadal trends were analysed against inter-annual variability in bloom timing and intensity, and environmental drivers (nutrient concentration, temperature, radiation level, wind speed).Spring blooms developed from the south to the north, with the first blooms peaking mid-March in the Bay of Mecklenburg and the latest bloom peaks occurring mid-April in the Gulf of Finland. Bloom duration was similar between sea areas (43 ± 2 day), except for shorter bloom duration in the Bay of Mecklenburg (36 ± 11 day). Variability in bloom timing increased towards the south. Bloom peak chlorophyll a concentrations were highest (and most variable) in the Gulf of Finland (20.2 ± 5.7 mg m-3) and the Bay of Mecklenburg (12.3 ± 5.2 mg m-3).Bloom peak chlorophyll a concentration showed a negative trend of -0.31 ± 0.10 mg m-3 yr-1. Trend-agnostic distribution-based (Weibull-type) bloom metrics showed a positive trend in bloom duration of 1.04 ± 0.20 day yr-1, which was not found with any of the threshold-based metrics. The Weibull bloom metric results were considered representative in the presence of bloom intensity trends.Bloom intensity was mainly determined by winter nutrient concentration, while bloom timing and duration co-varied with meteorological conditions. Longer blooms corresponded to higher water temperature, more intense solar radiation, and lower wind speed. It is concluded that nutrient reduction efforts led to decreasing bloom intensity, while changes in Baltic Sea environmental conditions associated with global change corresponded to a lengthening spring bloom period.

  4. Improved energy kinetics following high protein diet in McArdle's syndrome. A 31P magnetic resonance spectroscopy study

    DEFF Research Database (Denmark)

    Jensen, K E; Jakobsen, J; Thomsen, C

    1990-01-01

    A patient with McArdle's syndrome was examined using bicycle ergometry and 31P NMR spectroscopy during exercise. The patients working capacity was approximately half the expected capacity of controls. Muscle energy kinetics improved significantly during intravenous glucose infusion and after 6...... weeks of high protein diet. During intravenous infusion of amino acids, no changes in working capacity could be detected. No decrease was seen in intracellular muscle pH during aerobic exercise. A significant decrease in muscle pH during aerobic exercise was detected in all controls....

  5. Blocking of Exchange Proteins Directly Activated by cAMP Leads to Reduced Replication of Middle East Respiratory Syndrome Coronavirus

    Science.gov (United States)

    Tao, Xinrong; Mei, Feng; Agrawal, Anurodh; Peters, Clarence J.; Ksiazek, Thomas G.

    2014-01-01

    The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infections and diseases represents a potential threat for worldwide spread and requires development of effective therapeutic strategies. In this study, we revealed a novel positive function of an exchange protein directly activated by cyclic AMP 1 (cAMP-1; Epac-1) on MERS-CoV replication. Specifically, we have shown that Epac-specific inhibitor treatment or silencing Epac-1 gene expression rendered cells resistant to viral infection. We believe Epac-1 inhibitors deserve further study as potential therapeutic agents for MERS-CoV infection. PMID:24453361

  6. Nitrogenous nutrients promote the growth and toxicity of Dinophysis acuminata during estuarine bloom events.

    Directory of Open Access Journals (Sweden)

    Theresa K Hattenrath-Lehmann

    Full Text Available Diarrhetic Shellfish Poisoning (DSP is a globally significant human health syndrome most commonly caused by dinoflagellates within the genus Dinophysis. While blooms of harmful algae have frequently been linked to excessive nutrient loading, Dinophysis is a mixotrophic alga whose growth is typically associated with prey availability. Consequently, field studies of Dinophysis and nutrients have been rare. Here, the temporal dynamics of Dinophysis acuminata blooms, DSP toxins, and nutrients (nitrate, ammonium, phosphate, silicate, organic compounds were examined over four years within two New York estuaries (Meetinghouse Creek and Northport Bay. Further, changes in the abundance and toxicity of D. acuminata were assessed during a series of nutrient amendment experiments performed over a three year period. During the study, Dinophysis acuminata blooms exceeding one million cells L-1 were observed in both estuaries. Highly significant (p<0.001 forward stepwise multivariate regression models of ecosystem observations demonstrated that D. acuminata abundances were positively dependent on multiple environmental parameters including ammonium (p = 0.007 while cellular toxin content was positively dependent on ammonium (p = 0.002 but negatively dependent on nitrate (p<0.001. Nitrogen- (N and phosphorus- (P containing inorganic and organic nutrients significantly enhanced D. acuminata densities in nearly all (13 of 14 experiments performed. Ammonium significantly increased cell densities in 10 of 11 experiments, while glutamine significantly enhanced cellular DSP content in 4 of 5 experiments examining this compound. Nutrients may have directly or indirectly enhanced D. acuminata abundances as densities of this mixotroph during experiments were significantly correlated with multiple members of the planktonic community (phytoflagellates and Mesodinium. Collectively, this study demonstrates that nutrient loading and more specifically N-loading promotes the

  7. High-protein diet in lactation leads to a sudden infant death-like syndrome in mice.

    Directory of Open Access Journals (Sweden)

    Thomas Walther

    Full Text Available BACKGROUND: It is well accepted that reduced foetal growth and development resulting from maternal malnutrition are associated with a number of chronic conditions in later life. On the other hand such generation-transcending effects of over-nutrition and of high-protein consumption in pregnancy and lactation, a proven fact in all developed societies, are widely unknown. Thus, we intended to describe the generation-transcending effects of a high-protein diet, covering most relevant topics of human life like embryonic mortality, infant death, and physical health in later life. METHODS: Female mice received control food (21% protein or were fed a high protein diet (42% protein during mating. After fertilisation, females stayed on their respective diet until weaning. At birth, pups were put to foster mothers who were fed with standard food or with HP diet. After weaning, control diet was fed to all mice. All offspring were monitored up to 360 days after birth. We determined glucose-tolerance and measured cardiovascular parameters using a tip-catheter. Finally, abdominal fat amount was measured. RESULTS AND CONCLUSIONS: We identified a worried impact of high-protein diet during pregnancy on dams' body weight gain, body weight of newborns, number of offspring, and also survival in later life. Even more important is the discovery that high-protein diet during lactation caused a more than eight-fold increase in offspring mortality. The observed higher newborn mortality during lactation is a hitherto non-described, unique link to the still incompletely understood human sudden infant death syndrome (SIDS. Thus, although offspring of lactating mothers on high-protein diet might have the advantage of lower abdominal fat within the second half of life, this benefit seems not to compensate the immense risk of an early sudden death during lactation. Our data may implicate that both pregnant women and lactating mothers should not follow classical high-protein

  8. The spike protein of severe acute respiratory syndrome (SARS) is cleaved in virus infected Vero-E6 cells

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    Spike protein is one of the major structural proteins of severe acute respiratory syndrome-coronavirus. It is essential for the interaction of the virons with host cell receptors and subsequent fusion of the viral envelop with host cell membrane to allow infection. Some spike proteins of coronavirus, such as MHV, HCoV-OC43, AIBV and BcoV, are proteolytically cleaved into two subunits, S1 and S2. In contrast, TGV, FIPV and HCoV-229E are not. Many studies have shown that the cleavage of spike protein seriously affects its function. In order to investigate the maturation and proteolytic processing of the S protein of SARS CoV, we generated S1 and S2 subunit specific antibodies (Abs) as well as N, E and 3CL protein-specific Abs. Our results showed that the antibodies could efficiently and specifically bind to their corresponding proteins from E. coli expressed or lysate of SARS-CoV infected Vero-E6 cells by Western blot analysis. Furthermore, the anti-S 1 and S2 Abs were proved to be capable of binding to SARS CoV under electron microscope observation. When S2 Ab was used to perform immune precipitation with lysate of SARS-CoV infected cells, a cleaved S2 fragment was detected with S2-specific mAb by Western blot analysis. The data demonstrated that the cleavage of S protein was observed in the lysate, indicating that proteolytic processing of S protein is present in host cells.

  9. Monitoring for Harmful Algal Blooms in Influent Waters and Through Treatment on Lake Erie in the 2013 and 2014 Bloom Seasons 

    Science.gov (United States)

    Monitoring of Harmful Algal Blooms in Influent and Through Drinking Water Treatment Facilities Located on Lake Erie in the 2013 and 2014 Bloom SeasonsToby Sanan, Nicholas Dugan, Darren Lytle, Heath MashHarmful algal blooms (HABs) and their associated toxins are emerging as signif...

  10. The Blooming Anatomy Tool (BAT): A Discipline-Specific Rubric for Utilizing Bloom's Taxonomy in the Design and Evaluation of Assessments in the Anatomical Sciences

    Science.gov (United States)

    Thompson, Andrew R.; O'Loughlin, Valerie D.

    2015-01-01

    Bloom's taxonomy is a resource commonly used to assess the cognitive level associated with course assignments and examination questions. Although widely utilized in educational research, Bloom's taxonomy has received limited attention as an analytical tool in the anatomical sciences. Building on previous research, the Blooming Anatomy Tool (BAT)…

  11. Evaluation of Harmful Algal Bloom Outreach Activities

    Directory of Open Access Journals (Sweden)

    Richard Weisman

    2007-12-01

    Full Text Available With an apparent increase of harmful algal blooms (HABs worldwide,healthcare providers, public health personnel and coastal managers are struggling toprovide scientifically-based appropriately-targeted HAB outreach and education. Since1998, the Florida Poison Information Center-Miami, with its 24 hour/365 day/year freeAquatic Toxins Hotline (1-888-232-8635 available in several languages, has received over 25,000 HAB-related calls. As part of HAB surveillance, all possible cases of HAB-relatedillness among callers are reported to the Florida Health Department. This pilot studyevaluated an automated call processing menu system that allows callers to access bilingualHAB information, and to speak directly with a trained Poison Information Specialist. Themajority (68% of callers reported satisfaction with the information, and many provided specific suggestions for improvement. This pilot study, the first known evaluation of use and satisfaction with HAB educational outreach materials, demonstrated that the automated system provided useful HAB-related information for the majority of callers, and decreased the routine informational call workload for the Poison Information Specialists, allowing them to focus on callers needing immediate assistance and their healthcare providers. These results will lead to improvement of this valuable HAB outreach, education and surveillance tool. Formal evaluation is recommended for future HAB outreach and educational materials.

  12. [Progress in research on defective protein trafficking and functional restoration in HERG-associated long QT syndrome].

    Science.gov (United States)

    Fang, Peiliang; Lian, Jiangfang

    2016-02-01

    The human ether-a-go-go related gene (HERG) encodes the α -subunit of the rapid component of the delayed rectifier K(+) channel, which is essential for the third repolarization of the action potential of human myocardial cells. Mutations of the HERG gene can cause type II hereditary long QT syndrome (LQT2), characterized by prolongation of the QT interval, abnormal T wave, torsade de pointes, syncope and sudden cardiac death. So far more than 300 HERG mutations have been identified, the majority of which can cause LQT2 due to HERG protein trafficking defect. It has been reported that certain drugs can induce acquired long QT syndrome through directly blocking the pore and/or affecting the HERG trafficking. The trafficking defects and K(+) currents can be restored with low temperature and certain drugs. However, the mechanisms underlying defective trafficking caused by HERG mutations and the inhibition/restoration of HERG trafficking by drugs are still unknown. This review summarizes the current understanding of the molecular mechanisms including HERG trafficking under physiological and pathological conditions, and the effects of drugs on the HERG trafficking, in order to provide theoretical evidence for the diagnosis and treatment of long QT syndrome.

  13. Chlorophyll Blooms in the Oligotropic Gyres: Ocean oases?

    Science.gov (United States)

    Wilson, C.; Maximenko, N.

    2005-12-01

    Ocean color images from the SeaWiFS satellite have revealed that large blooms of chlorophyll sometimes develop in late summer northeast of Hawaii in the oligotrophic Pacific. While these blooms are a recurrent feature, appearing almost every year, their existence was only recently discovered from satellite imagery of ocean color. They have been observed in 11 of 16 years of satellite ocean color data (CZCS, OCTS and SeaWiFS), can last up to 4-5 months, and can get as big as the state of California. Since the blooms have never been purposely sampled, it remains uncertain what species they are composed of, what mechanisms supply nutrients to support the elevated biomass, and what their impacts are on higher trophic levels. However, conventional scenarios of upwelled nutrients or enhanced mixing deepening the mixed layer into the nutricline do not seem to be operable. Instead, research has suggested that the source of new nutrients is biologically mediated, either by nitrogen fixing organisms, or by the vertical migration of diatom mats below the nutricline. Physical dynamics affect the blooms on a basin-wide scale. The blooms only appear in the eastern gyre of the Pacific, a closed anticyclonic gyre that has enhanced convergence relative to the rest of the Pacific, suggesting that blooms develop in part from a large-scale aggregation of the buoyant organisms proposed to be associated with them. While these proposed biological and physical dynamics are speculative, if similar blooms appear in other oceans, analysis of the common features of their physical environments will help to better pinpoint the physical forcings involved. Analysis of the global fields of SeaWiFS satellite chlorophyll shows that while not nearly as common as in the North Pacific, potentially similar blooms occur in the North and South Atlantic, and the North Indian Oceans, but not in the S. Pacific. However, unlike in the N. Pacific, these blooms are not always associated with strong convergence

  14. A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse)

    OpenAIRE

    Zhou, Yihua; Xu, Bixiong C.; Maheshwari, Hiralal G.; He, Li; Reed, Michael; Lozykowski, Maria; Okada, Shigeru; Cataldo, Lori; Coschigamo, Karen; Wagner, Thomas E.; Baumann, Gerhard; Kopchick, John J.

    1997-01-01

    Laron syndrome [growth hormone (GH) insensitivity syndrome] is a hereditary dwarfism resulting from defects in the GH receptor (GHR) gene. GHR deficiency has not been reported in mammals other than humans. Many aspects of GHR dysfunction remain unknown because of ethical and practical limitations in studying humans. To create a mammalian model for this disease, we generated mice bearing a disrupted GHR/binding protein (GHR/BP) gene through a homologous gene targeting approach. Homozygous GHR/...

  15. The effects of exercise on C-reactive protein, insulin, leptin and some cardiometabolic risk factors in Egyptian children with or without metabolic syndrome

    OpenAIRE

    Kamal Nashwa; Ragy Merhan

    2012-01-01

    Abstract Background The prevalence and magnitude of obesity in the children and the adolescents have increased dramatically in the developing countries over the last 20–30 years. The prevalence of metabolic syndrome (MS) in children is increasing. Aim: This study aimed to investigate the changes of C-reactive protein (CRP), leptin, insulin, and blood lipids before and after the exercise therapy in normal and obese children (with or without metabolic syndrome). Methods The study covered 49 nor...

  16. Allergen cross-reactivity in allergic rhinitis and oral-allergy syndrome: a bioinformatic protein sequence analysis.

    Science.gov (United States)

    Platt, Michael; Howell, Sara; Sachdeva, Ricky; Dumont, Charles

    2014-07-01

    Clinical allergy cross-reactivity that is seen with related inhalant allergens or between unrelated inhalant allergens and foods in oral allergy syndrome (OAS) remains poorly understood. The goal of this study is to determine whether clinical cross-reactivity can be identified from primary protein sequences in allergy epitopes and food proteins. High-throughput analysis was performed by assembling all known allergy epitopes within the Immune Epitope Database (IEDB; http://www.iedb.org) for 5 common species from 5 inhalant allergen subclasses and comparing their protein sequences to each other, as well as to sequences of intact proteins from known cross-reactive foods in the European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI) protein database (http://www.uniprot.org) that have been implicated in OAS. Computational methods were employed to allow for exact matching, gaps, and similar amino acids using multiple algorithms. A phylogenetic tree was created to determine evolutionary relationships between cross-reactive epitopes in OAS. Twenty-three common inhalant allergens had 4429 unique epitopes; the 19 foods implicated in OAS had 9497 protein sequences. The Basic Local Alignment Search Tool (BLAST) algorithm identified interclass and intraclass sequence similarities for the 5 inhalant allergy classes with high similarity for mites, grasses, and trees. Analysis of OAS proteins identified 104 matches to inhalant allergy epitopes that are known to cross-react. The phylogenetic tree displayed relationships that mostly followed organism phylogeny. Use of primary protein sequences was successful in explaining clinical allergy cross-reactivity. Clinical correlation is needed for use of these epitopes as diagnostic or therapeutic entities for patients with cross-reactive allergic disease. © 2014 ARS-AAOA, LLC.

  17. Comparison of high-protein diets and leucine supplementation in the prevention of metabolic syndrome and related disorders in mice.

    Science.gov (United States)

    Freudenberg, Anne; Petzke, Klaus J; Klaus, Susanne

    2012-11-01

    High-protein diets have been shown to promote weight loss, to improve glucose homeostasis and to increase energy expenditure and fat oxidation. We aimed to study whether leucine supplementation is able to mimic the alleviating effects of high-protein diets on metabolic syndrome parameters in mice fed high-fat diet. Male C57BL/6 mice were fed for 20 weeks with semisynthetic high-fat diets (20% w/w of fat) containing either an adequate (10% protein, AP) or high (50% protein, HP) amount of whey protein, or an AP diet supplemented with L-leucine corresponding to the leucine content of the HP diet (6% leucine, AP+L). Body weight and composition, energy expenditure, glucose tolerance, hepatic triacylglycerols (TG), plasma parameters as well as expression levels of mRNA and proteins in different tissues were measured. HP feeding resulted in decreased body weight, body fat and hepatic TG accumulation, as well as increased insulin sensitivity compared to AP. This was linked to an increased total and resting energy expenditure (REE), decreased feed energy efficiency, increased skeletal muscle (SM) protein synthesis, reduced hepatic lipogenesis and increased white fat lipolysis. Leucine supplementation had effects that were intermediate between HP and AP with regard to body composition, liver TG content, insulin sensitivity, REE and feed energy efficiency, and similar effects as HP on SM protein synthesis. However, neither HP nor AP+L showed an activation of the mammalian target of rapamycin pathway in SM. Leucine supplementation had no effect on liver lipogenesis and white fat lipolysis compared to AP. It is concluded that the essential amino acid leucine is able to mimic part but not all beneficial metabolic effects of HP diets.

  18. Improving Bloom Filter Performance on Sequence Data Using k-mer Bloom Filters.

    Science.gov (United States)

    Pellow, David; Filippova, Darya; Kingsford, Carl

    2017-06-01

    Using a sequence's k-mer content rather than the full sequence directly has enabled significant performance improvements in several sequencing applications, such as metagenomic species identification, estimation of transcript abundances, and alignment-free comparison of sequencing data. As k-mer sets often reach hundreds of millions of elements, traditional data structures are often impractical for k-mer set storage, and Bloom filters (BFs) and their variants are used instead. BFs reduce the memory footprint required to store millions of k-mers while allowing for fast set containment queries, at the cost of a low false positive rate (FPR). We show that, because k-mers are derived from sequencing reads, the information about k-mer overlap in the original sequence can be used to reduce the FPR up to 30 × with little or no additional memory and with set containment queries that are only 1.3 - 1.6 times slower. Alternatively, we can leverage k-mer overlap information to store k-mer sets in about half the space while maintaining the original FPR. We consider several variants of such k-mer Bloom filters (kBFs), derive theoretical upper bounds for their FPR, and discuss their range of applications and limitations.

  19. Self-Organizing Feature Maps Identify Proteins Critical to Learning in a Mouse Model of Down Syndrome

    Science.gov (United States)

    Higuera, Clara; Gardiner, Katheleen J.; Cios, Krzysztof J.

    2015-01-01

    Down syndrome (DS) is a chromosomal abnormality (trisomy of human chromosome 21) associated with intellectual disability and affecting approximately one in 1000 live births worldwide. The overexpression of genes encoded by the extra copy of a normal chromosome in DS is believed to be sufficient to perturb normal pathways and normal responses to stimulation, causing learning and memory deficits. In this work, we have designed a strategy based on the unsupervised clustering method, Self Organizing Maps (SOM), to identify biologically important differences in protein levels in mice exposed to context fear conditioning (CFC). We analyzed expression levels of 77 proteins obtained from normal genotype control mice and from their trisomic littermates (Ts65Dn) both with and without treatment with the drug memantine. Control mice learn successfully while the trisomic mice fail, unless they are first treated with the drug, which rescues their learning ability. The SOM approach identified reduced subsets of proteins predicted to make the most critical contributions to normal learning, to failed learning and rescued learning, and provides a visual representation of the data that allows the user to extract patterns that may underlie novel biological responses to the different kinds of learning and the response to memantine. Results suggest that the application of SOM to new experimental data sets of complex protein profiles can be used to identify common critical protein responses, which in turn may aid in identifying potentially more effective drug targets. PMID:26111164

  20. The 7a accessory protein of severe acute respiratory syndrome coronavirus acts as an RNA silencing suppressor.

    Science.gov (United States)

    Karjee, Sumona; Minhas, Ankita; Sood, Vikas; Ponia, Sanket S; Banerjea, Akhil C; Chow, Vincent T K; Mukherjee, Sunil K; Lal, Sunil K

    2010-10-01

    RNA silencing suppressors (RSSs) are well studied for plant viruses but are not well defined to date for animal viruses. Here, we have identified an RSS from a medically important positive-sense mammalian virus, Severe acute respiratory syndrome coronavirus. The viral 7a accessory protein suppressed both transgene and virus-induced gene silencing by reducing the levels of small interfering RNA (siRNA). The suppression of silencing was analyzed by two independent assays, and the middle region (amino acids [aa] 32 to 89) of 7a was responsible for suppression. Finally, the RNA suppression property and the enhancement of heterologous replicon activity by the 7a protein were confirmed for animal cell lines.

  1. Intrachromosomal recombination between highly diverged DNA sequences is enabled in human cells deficient in Bloom helicase.

    Science.gov (United States)

    Wang, Yibin; Li, Shen; Smith, Krissy; Waldman, Barbara Criscuolo; Waldman, Alan S

    2016-05-01

    Mutation of Bloom helicase (BLM) causes Bloom syndrome (BS), a rare human genetic disorder associated with genome instability, elevation of sister chromatid exchanges, and predisposition to cancer. Deficiency in BLM homologs in Drosophila and yeast brings about significantly increased rates of recombination between imperfectly matched sequences ("homeologous recombination," or HeR). To assess whether BLM deficiency provokes an increase in HeR in human cells, we transfected an HeR substrate into a BLM-null cell line derived from a BS patient. The substrate contained a thymidine kinase (tk)-neo fusion gene disrupted by the recognition site for endonuclease I-SceI, as well as a functional tk gene to serve as a potential recombination partner for the tk-neo gene. The two tk sequences on the substrate displayed 19% divergence. A double-strand break was introduced by expression of I-SceI and repair events were recovered by selection for G418-resistant clones. Among 181 events recovered, 30 were accomplished via HeR with the balance accomplished by nonhomologous end-joining. The frequency of HeR events in the BS cells was elevated significantly compared to that seen in normal human fibroblasts or in BS cells complemented for BLM expression. We conclude that BLM deficiency enables HeR in human cells.

  2. Downregulation of the Werner syndrome protein induces a metabolic shift that compromises redox homeostasis and limits proliferation of cancer cells.

    Science.gov (United States)

    Li, Baomin; Iglesias-Pedraz, Juan Manuel; Chen, Leng-Ying; Yin, Fei; Cadenas, Enrique; Reddy, Sita; Comai, Lucio

    2014-04-01

    The Werner syndrome protein (WRN) is a nuclear protein required for cell growth and proliferation. Loss-of-function mutations in the Werner syndrome gene are associated with the premature onset of age-related diseases. How loss of WRN limits cell proliferation and induces replicative senescence is poorly understood. Here, we show that WRN depletion leads to a striking metabolic shift that coordinately weakens the pathways that generate reducing equivalents for detoxification of reactive oxygen species and increases mitochondrial respiration. In cancer cells, this metabolic shift counteracts the Warburg effect, a defining characteristic of many malignant cells, resulting in altered redox balance and accumulation of oxidative DNA damage that inhibits cell proliferation and induces a senescence-like phenotype. Consistent with these findings, supplementation with antioxidant rescues at least in part cell proliferation and decreases senescence in WRN-knockdown cancer cells. These results demonstrate that WRN plays a critical role in cancer cell proliferation by contributing to the Warburg effect and preventing metabolic stress.

  3. ABHD5/CGI-58, the Chanarin-Dorfman Syndrome Protein, Mobilises Lipid Stores for Hepatitis C Virus Production

    Science.gov (United States)

    Vieyres, Gabrielle; Welsch, Kathrin; Gerold, Gisa; Gentzsch, Juliane; Kahl, Sina; Vondran, Florian W. R.; Kaderali, Lars; Pietschmann, Thomas

    2016-01-01

    Hepatitis C virus (HCV) particles closely mimic human very-low-density lipoproteins (VLDL) to evade humoral immunity and to facilitate cell entry. However, the principles that govern HCV association with VLDL components are poorly defined. Using an siRNA screen, we identified ABHD5 (α/β hydrolase domain containing protein 5, also known as CGI-58) as a new host factor promoting both virus assembly and release. ABHD5 associated with lipid droplets and triggered their hydrolysis. Importantly, ABHD5 Chanarin-Dorfman syndrome mutants responsible for a rare lipid storage disorder in humans were mislocalised, and unable to consume lipid droplets or support HCV production. Additional ABHD5 mutagenesis revealed a novel tribasic motif that does not influence subcellular localization but determines both ABHD5 lipolytic and proviral properties. These results indicate that HCV taps into the lipid droplet triglyceride reservoir usurping ABHD5 lipase cofactor function. They also suggest that the resulting lipid flux, normally devoted to VLDL synthesis, also participates in the assembly and release of the HCV lipo-viro-particle. Altogether, our study provides the first association between the Chanarin-Dorfman syndrome protein and an infectious disease and sheds light on the hepatic manifestations of this rare genetic disorder as well as on HCV morphogenesis. PMID:27124600

  4. ABHD5/CGI-58, the Chanarin-Dorfman Syndrome Protein, Mobilises Lipid Stores for Hepatitis C Virus Production.

    Directory of Open Access Journals (Sweden)

    Gabrielle Vieyres

    2016-04-01

    Full Text Available Hepatitis C virus (HCV particles closely mimic human very-low-density lipoproteins (VLDL to evade humoral immunity and to facilitate cell entry. However, the principles that govern HCV association with VLDL components are poorly defined. Using an siRNA screen, we identified ABHD5 (α/β hydrolase domain containing protein 5, also known as CGI-58 as a new host factor promoting both virus assembly and release. ABHD5 associated with lipid droplets and triggered their hydrolysis. Importantly, ABHD5 Chanarin-Dorfman syndrome mutants responsible for a rare lipid storage disorder in humans were mislocalised, and unable to consume lipid droplets or support HCV production. Additional ABHD5 mutagenesis revealed a novel tribasic motif that does not influence subcellular localization but determines both ABHD5 lipolytic and proviral properties. These results indicate that HCV taps into the lipid droplet triglyceride reservoir usurping ABHD5 lipase cofactor function. They also suggest that the resulting lipid flux, normally devoted to VLDL synthesis, also participates in the assembly and release of the HCV lipo-viro-particle. Altogether, our study provides the first association between the Chanarin-Dorfman syndrome protein and an infectious disease and sheds light on the hepatic manifestations of this rare genetic disorder as well as on HCV morphogenesis.

  5. Physical and biological data collected along the Texas, Mississippi, and Florida Gulf coasts in the Gulf of Mexico as part of the Harmful Algal BloomS Observing System from 19 Aug 1953 to 11 July 2014 (NODC Accession 0120767)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — HABSOS (Harmful Algal BloomS Observing System) is a data collection and distribution system for harmful algal bloom (HAB) information in the Gulf of Mexico. The goal...

  6. CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome

    NARCIS (Netherlands)

    Batsukh, Tserendulam; Pieper, Lasse; Koszucka, Anna M.; von Velsen, Nina; Hoyer-Fender, Sigrid; Elbracht, Miriam; Bergman, Jorieke E. H.; Hoefsloot, Lies H.; Pauli, Silke

    2010-01-01

    CHARGE syndrome is an autosomal dominant disorder caused in about two-third of cases by mutations in the CHD7 gene. For other genetic diseases e.g. hereditary spastic paraplegia, it was shown that interacting partners are involved in the underlying cause of the disease. These data encouraged us to s

  7. Mutations of the CEP290 gene encoding a centrosomal protein cause Meckel-Gruber syndrome.

    NARCIS (Netherlands)

    Frank, V.; Hollander, A.I. den; Bruchle, N.O.; Zonneveld, M.N.; Nurnberg, G.; Becker, C.; Bois, G. Du; Kendziorra, H.; Roosing, S.; Senderek, J.; Nurnberg, P.; Cremers, F.P.M.; Zerres, K.; Bergmann, C.

    2008-01-01

    Meckel-Gruber syndrome (MKS) is an autosomal recessive, lethal multisystemic disorder characterized by meningooccipital encephalocele, cystic kidney dysplasia, hepatobiliary ductal plate malformation, and postaxial polydactyly. Recently, genes for MKS1 and MKS3 were identified, putting MKS on the li

  8. Cockayne syndrome group B protein prevents the accumulation of damaged mitochondria by promoting mitochondrial autophagy

    DEFF Research Database (Denmark)

    Scheibye-Knudsen, Morten; Ramamoorthy, Mahesh; Sykora, Peter

    2012-01-01

    Cockayne syndrome (CS) is a devastating autosomal recessive disease characterized by neurodegeneration, cachexia, and accelerated aging. 80% of the cases are caused by mutations in the CS complementation group B (CSB) gene known to be involved in DNA repair and transcription. Recent evidence indi...

  9. Pulmonary Thromboembolism in Klinefelter%u2019s Syndrome Patient with Deficient of Protein C

    Directory of Open Access Journals (Sweden)

    Mehmet Yigit

    2013-08-01

    Full Text Available Klinefelter syndrome (KS is a common genetic disorder caused by one or more supernumerary X chromosomes. KS poses an increased risk for venous thromboembolic events such as deep venous thrombosis and pulmonary embolism. Klinefelter syndrome is prone to hypercoagulability due to hormonal imbalance and one or more inherited thrombophilic factors. Therefore, patients with KS having a medical history of venous thromboembolism require chest computed tomographic (CT images and oral anticoagulation therapy for a period of at least six months. A 21 year old, male patient diagnosed with Klinefelter syndrome was presented to the emergency department of our hospital with primary complaints of left lower extremity pain lasting for 2 months. Deep venous thromboembosis (DVT was diagnosed via venous doppler ultrasound and pulmonary thromboembolism in his chest CT images. Following anticoagulation treatment, his symptoms recovered. An endocrinologic test should be ordered in patients having klinefelter syndrome with a medical or familial history of venous thromboembolism as well as additional assessment of innate or acquired thrombophilia should be made.

  10. Genetics Home Reference: Potocki-Shaffer syndrome

    Science.gov (United States)

    ... Romeike BF, Wuyts W. Proximal chromosome 11p contiguous gene deletion syndrome phenotype: case report and review of the literature. Clin Neuropathol. 2007 Jan-Feb;26(1):1-11. Review. Citation on PubMed Swarr DT, Bloom D, Lewis RA, Elenberg E, Friedman EM, Glotzbach C, Wissman ...

  11. Studies of the viral binding proteins of shrimp BP53, a receptor of white spot syndrome virus.

    Science.gov (United States)

    Li, Chen; Gao, Xiao-Xiao; Huang, Jie; Liang, Yan

    2016-02-01

    The specific binding between viral attachment proteins (VAPs) of a virus and its cellular receptors on host cells mediates virus entry into host cells, which triggers subsequent viral infections. Previous studies indicate that F1 ATP synthase β subunit (named BP53), is found on the surface of shrimp cells and involved in white spot syndrome virus (WSSV) infection by functioning as a potential viral receptor. Herein, in a far-western blotting assay, three WSSV proteins with molecular weights of 28 kDa, 37 kDa, and >50 kDa were found to interact with BP53. The 28 kDa and 37 kDa proteins were identified as the envelope protein VP28 and VP37 of WSSV respectively, which could be recognized by the polyclonal antibodies. Enzyme-linked immunosorbent binding assays revealed that VP37 contributed to almost 80% of the binding capability for BP53 compared with the same amount of total WSSV protein. The relationship between BP53 and its complementary interacting protein, VP37, was visualized using a co-localization assay. Bound VP37 on the cell surface co-localized with BP53 and shared a similar subcellular location on the outer surface of shrimp cells. Pearson's correlation coefficients reached to 0.67 ± 0.05 and the Mander's overlap coefficients reached 0.70 ± 0.05, which indicated a strong relationship between the localization of BP53 and bound rVP37. This provides evidence for an interaction between BP53 and VP37 obtained at the molecular and cellular levels, supporting the hypothesis that BP53 serves as a receptor for WSSV by binding to VP37. The identification of the viral binding proteins of shrimp BP53 is helpful for better understanding the pathogenic mechanisms of WSSV to infect shrimp at the cellular level.

  12. Endogenous RGS proteins modulate SA and AV nodal functions in isolated heart: implications for sick sinus syndrome and AV block.

    Science.gov (United States)

    Fu, Ying; Huang, Xinyan; Piao, Lin; Lopatin, Anatoli N; Neubig, Richard R

    2007-05-01

    G protein-coupled receptors play a pivotal role in regulating cardiac automaticity. Their function is controlled by regulator of G protein signaling (RGS) proteins acting as GTPase-activating proteins for Galpha subunits to suppress Galpha(i) and Galpha(q) signaling. Using knock-in mice in which Galpha(i2)-RGS binding and negative regulation are disrupted by a genomic Galpha(i2)G184S (GS) point mutation, we recently (Fu Y, Huang X, Zhong H, Mortensen RM, D'Alecy LG, Neubig RR. Circ Res 98: 659-666, 2006) showed that endogenous RGS proteins suppress muscarinic receptor-mediated bradycardia. To determine whether this was due to direct regulation of cardiac pacemakers or to alterations in the central nervous system or vascular responses, we examined isolated, perfused hearts. Isoproterenol-stimulated beating rates of heterozygote (+/GS) and homozygote (GS/GS) hearts were significantly more sensitive to inhibition by carbachol than were those of wild type (+/+). Even greater effects were seen in the absence of isoproterenol; the potency of muscarinic-mediated bradycardia was enhanced fivefold in GS/GS and twofold in +/GS hearts compared with +/+. A(1)-adenosine receptor-mediated bradycardia was unaffected. In addition to effects on the sinoatrial node, +/GS and GS/GS hearts show significantly increased carbachol-induced third-degree atrioventricular (AV) block. Atrial pacing studies demonstrated an increased PR interval and AV effective refractory period in GS/GS hearts compared with +/+. Thus loss of the inhibitory action of endogenous RGS proteins on Galpha(i2) potentiates muscarinic inhibition of cardiac automaticity and conduction. The severe carbachol-induced sinus bradycardia in Galpha(i2)G184S mice suggests a possible role for alterations of Galpha(i2) or RGS proteins in sick sinus syndrome and pathological AV block.

  13. Protein dynamics associated with failed and rescued learning in the Ts65Dn mouse model of Down syndrome.

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    Md Mahiuddin Ahmed

    Full Text Available Down syndrome (DS is caused by an extra copy of human chromosome 21 (Hsa21. Although it is the most common genetic cause of intellectual disability (ID, there are, as yet, no effective pharmacotherapies. The Ts65Dn mouse model of DS is trisomic for orthologs of ∼55% of Hsa21 classical protein coding genes. These mice display many features relevant to those seen in DS, including deficits in learning and memory (L/M tasks requiring a functional hippocampus. Recently, the N-methyl-D-aspartate (NMDA receptor antagonist, memantine, was shown to rescue performance of the Ts65Dn in several L/M tasks. These studies, however, have not been accompanied by molecular analyses. In previous work, we described changes in protein expression induced in hippocampus and cortex in control mice after exposure to context fear conditioning (CFC, with and without memantine treatment. Here, we extend this analysis to Ts65Dn mice, measuring levels of 85 proteins/protein modifications, including components of MAP kinase and MTOR pathways, and subunits of NMDA receptors, in cortex and hippocampus of Ts65Dn mice after failed learning in CFC and after learning was rescued by memantine. We show that, compared with wild type littermate controls, (i of the dynamic responses seen in control mice in normal learning, >40% also occur in Ts65Dn in failed learning or are compensated by baseline abnormalities, and thus are considered necessary but not sufficient for successful learning, and (ii treatment with memantine does not in general normalize the initial protein levels but instead induces direct and indirect responses in approximately half the proteins measured and results in normalization of the endpoint protein levels. Together, these datasets provide a first view of the complexities associated with pharmacological rescue of learning in the Ts65Dn. Extending such studies to additional drugs and mouse models of DS will aid in identifying pharmacotherapies for effective

  14. Redox proteomics analysis of HNE-modified proteins in Down syndrome brain: clues for understanding the development of Alzheimer disease.

    Science.gov (United States)

    Di Domenico, Fabio; Pupo, Gilda; Tramutola, Antonella; Giorgi, Alessandra; Schininà, Maria Eugenia; Coccia, Raffaella; Head, Elizabeth; Butterfield, D Allan; Perluigi, Marzia

    2014-06-01

    Down syndrome (DS) is the most common genetic cause of intellectual disability, due to partial or complete triplication of chromosome 21. DS subjects are characterized by a number of abnormalities including premature aging and development of Alzheimer disease (AD) neuropathology after approximately 40 years of age. Several studies show that oxidative stress plays a crucial role in the development of neurodegeneration in the DS population. Increased lipid peroxidation is one of the main events causing redox imbalance within cells through the formation of toxic aldehydes that easily react with DNA, lipids, and proteins. In this study we used a redox proteomics approach to identify specific targets of 4-hydroxynonenal modifications in the frontal cortex from DS cases with and without AD pathology. We suggest that a group of identified proteins followed a specific pattern of oxidation in DS vs young controls, probably indicating characteristic features of the DS phenotype; a second group of identified proteins showed increased oxidation in DS/AD vs DS, thus possibly playing a role in the development of AD. The third group of comparison, DS/AD vs old controls, identified proteins that may be considered specific markers of AD pathology. All the identified proteins are involved in important biological functions including intracellular quality control systems, cytoskeleton network, energy metabolism, and antioxidant response. Our results demonstrate that oxidative damage is an early event in DS, as well as dysfunctions of protein-degradation systems and cellular protective pathways, suggesting that DS subjects are more vulnerable to oxidative damage accumulation that might contribute to AD development. Further, considering that the majority of proteins have been already demonstrated to be oxidized in AD brain, our results strongly support similarities with AD in DS.

  15. Harmful Freshwater Algal Blooms, With an Emphasis on Cyanobacteria

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    Hans W. Paerl

    2001-01-01

    Full Text Available Suspended algae, or phytoplankton, are the prime source of organic matter supporting food webs in freshwater ecosystems. Phytoplankton productivity is reliant on adequate nutrient supplies; however, increasing rates of nutrient supply, much of it manmade, fuels accelerating primary production or eutrophication. An obvious and problematic symptom of eutrophication is rapid growth and accumulations of phytoplankton, leading to discoloration of affected waters. These events are termed blooms. Blooms are a prime agent of water quality deterioration, including foul odors and tastes, deoxygenation of bottom waters (hypoxia and anoxia, toxicity, fish kills, and food web alterations. Toxins produced by blooms can adversely affect animal (including human health in waters used for recreational and drinking purposes. Numerous freshwater genera within the diverse phyla comprising the phytoplankton are capable of forming blooms; however, the blue-green algae (or cyanobacteria are the most notorious bloom formers. This is especially true for harmful toxic, surface-dwelling, scum-forming genera (e.g., Anabaena, Aphanizomenon, Nodularia, Microcystis and some subsurface bloom-formers (Cylindrospermopsis, Oscillatoria that are adept at exploiting nutrient-enriched conditions. They thrive in highly productive waters by being able to rapidly migrate between radiance-rich surface waters and nutrient-rich bottom waters. Furthermore, many harmful species are tolerant of extreme environmental conditions, including very high light levels, high temperatures, various degrees of desiccation, and periodic nutrient deprivation. Some of the most noxious cyanobacterial bloom genera (e.g., Anabaena, Aphanizomenon, Cylindrospermopsis, Nodularia are capable of fixing atmospheric nitrogen (N2, enabling them to periodically dominate under nitrogen-limited conditions. Cyanobacteria produce a range of organic compounds, including those that are toxic to higher-ranked consumers, from

  16. Optical detection of Prorocentrum donghaiense blooms based on multispectral reflectance

    Institute of Scientific and Technical Information of China (English)

    TAO Bangyi; PAN Delu; MAO Zhihua; SHEN Yuzhang; ZHU Qiankun; CHEN Jianyu

    2013-01-01

    Prorocentrum donghaiense is one of the most common red tide causative dinoflagellates in the Changjiang (Yangtze) River Estuary and the adjacent area of the East China Sea. It causes large-scale blooms in late spring and early summer that lead to widespread ecologic and economic damage. A means for distinguish-ing dinoflagellate blooms from diatom (Skeletonema costatum) blooms is desired. On the basis of measure-ments of remote sensing reflectance [Rrs(λ)] and inherent optical parameters, the potential of using a mul-tispectral approach is assessed for discriminating the algal blooms due to P. donghaiense from those due to S. costatum. The behavior of two reflectance ratios [R1 =Rrs(560)/Rrs(532) and R2 =Rrs(708)/Rrs(665)], suggests that differentiation of P. donghaiense blooms from diatom bloom types is possible from the current band setup of ocean color sensors. It is found that there are two reflectance ratio regimes that indicate a bloom is dominated by P. donghaiense: (1) R1 >1.55 and R2 1.75 and R2 ?1.0. Various sensitivity analyses are conducted to investigate the effects of the variation in varying levels of chlorophyll concentration and colored dissolved organic matter (CDOM) as well as changes in the backscattering ratio (bbp/bp) on the efficacy of this multispectral approach. Results indicate that the intensity and inherent op-tical properties of the algal species explain much of the behavior of the two ratios. Although backscattering influences the amplitude of Rrs(λ), especially in the 530 and 560 nm bands, the discrimination between P. donghaiense and diatoms is not significantly affected by the variation of bbp/bp. Since a CDOM(440) in coastal areas of the ECS is typically lower than 1.0 m−1 in most situations, the presence of CDOM does not interfere with this discrimination, even as SCDOM varies from 0.01 to 0.026 nm−1. Despite all of these effects, the dis-crimination of P. donghaiense blooms from diatom blooms based on multispectral

  17. Climbing Bloom's taxonomy pyramid: Lessons from a graduate histology course.

    Science.gov (United States)

    Zaidi, Nikki B; Hwang, Charles; Scott, Sara; Stallard, Stefanie; Purkiss, Joel; Hortsch, Michael

    2017-02-23

    Bloom's taxonomy was adopted to create a subject-specific scoring tool for histology multiple-choice questions (MCQs). This Bloom's Taxonomy Histology Tool (BTHT) was used to analyze teacher- and student-generated quiz and examination questions from a graduate level histology course. Multiple-choice questions using histological images were generally assigned a higher BTHT level than simple text questions. The type of microscopy technique (light or electron microscopy) used for these image-based questions did not result in any significant differences in their Bloom's taxonomy scores. The BTHT levels for teacher-generated MCQs correlated positively with higher discrimination indices and inversely with the percent of students answering these questions correctly (difficulty index), suggesting that higher-level Bloom's taxonomy questions differentiate well between higher- and lower-performing students. When examining BTHT scores for MCQs that were written by students in a Multiple-Choice Item Development Assignment (MCIDA) there was no significant correlation between these scores and the students' ability to answer teacher-generated MCQs. This suggests that the ability to answer histology MCQs relies on a different skill set than the aptitude to construct higher-level Bloom's taxonomy questions. However, students significantly improved their average BTHT scores from the midterm to the final MCIDA task, which indicates that practice, experience and feedback increased their MCQ writing proficiency. Anat Sci Educ. © 2017 American Association of Anatomists.

  18. Thermal blooming on laser propagation in an aspirating pipe

    Science.gov (United States)

    Zhu, Fuyin; Wang, Jihong; Ren, Ge; Tan, Yufeng; Zhu, Nengbing; Ai, Zhiwei

    2016-10-01

    Thermal blooming effect of gas on laser propagation can seriously degrade performance of far-field beam quality and energy distribution. Numerical simulation is carried out to study the influences of thermal blooming on laser propagation in line pipes. A physical model of thermal blooming effect of gas on laser propagation in an aspirating pipe is established. Axial flow and suction in the outlet are used to attenuate the thermal blooming effect. Based on the computational fluid dynamics (CFD) software, stable calculation of flow field is carried out first, then the optical field and the fluent field is coupling calculated by means of user defined function (UDF). The results show that radial flow is enhanced in the aspirating pipe and the index of refraction gradient caused by thermal blooming effect is decreased. It is indicated that the beam quality of the outlet is improved compared with the pipe model without aspirating. The optical path difference (OPD) distribution of the outlet is analyzed and decomposed by Zernike polynomials. It is shown that the defocus item of 4m aspirating pipe is decreased more than an order of magnitude compared with the 4m pipe without aspirating.

  19. Toxicity of harmful cyanobacterial blooms to bream and roach.

    Science.gov (United States)

    Trinchet, Isabelle; Cadel-Six, Sabrina; Djediat, Chakib; Marie, Benjamin; Bernard, Cécile; Puiseux-Dao, Simone; Krys, Sophie; Edery, Marc

    2013-09-01

    Aquatic ecosystems are facing increasing environmental pressures, leading to an increasing frequency of cyanobacterial Harmful Algal Blooms (cHABs) that have emerged as a worldwide concern due to their growing frequency and their potential toxicity to the fauna that threatens the functioning of ecosystems. Cyanobacterial blooms raise concerns due to the fact that several strains produce potent bioactive or toxic secondary metabolites, such as the microcystins (MCs), which are hepatotoxic to vertebrates. These strains of cyanobacteria may be potentially toxic to fish via gastrointestinal ingestion and also by direct absorption of the toxin MC from the water. The purpose of our study was to investigate toxic effects observed in fish taken from several lakes in the Ile-de-France region, where MCs-producing blooms occur. This study comprises histological studies and the measurement of MC concentrations in various organs. The histological findings are similar to those obtained following laboratory exposure of medaka fish to MCs: hepatic lesions predominate and include cell lysis and cell detachment. MC concentrations in the organs revealed that accumulation was particularly high in the digestive tract and the liver, which are known to be classical targets of MCs. In contrast concentrations were very low in the muscles. Differences in the accumulation of MC variants produced by blooms indicate that in order to more precisely evaluate the toxic potential of a specific bloom it is necessary not only to consider the concentration of toxins, but also the variants produced.

  20. Bloom Helicase and DNA Topoisomerase IIIα Are Involved in the Dissolution of Sister Chromatids

    Science.gov (United States)

    Seki, Masayuki; Nakagawa, Takayuki; Seki, Takahiko; Kato, Genta; Tada, Shusuke; Takahashi, Yuriko; Yoshimura, Akari; Kobayashi, Takayuki; Aoki, Ayako; Otsuki, Makoto; Habermann, Felix A.; Tanabe, Hideyuki; Ishii, Yutaka; Enomoto, Takemi

    2006-01-01

    Bloom's syndrome (BS) is an autosomal disorder characterized by predisposition to a wide variety of cancers. The gene product whose mutation leads to BS is the RecQ family helicase BLM, which forms a complex with DNA topoisomerase IIIα (Top3α). However, the physiological relevance of the interaction between BLM and Top3α within the cell remains unclear. We show here that Top3α depletion causes accumulation of cells in G2 phase, enlargement of nuclei, and chromosome gaps and breaks that occur at the same position in sister chromatids. The transition from metaphase to anaphase is also inhibited. All of these phenomena except cell lethality are suppressed by BLM gene disruption. Taken together with the biochemical properties of BLM and Top3α, these data indicate that BLM and Top3α execute the dissolution of sister chromatids. PMID:16880537

  1. Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein.

    Science.gov (United States)

    Tang, Maoxue; Gao, Guangping; Rueda, Carlos B; Yu, Hang; Thibodeaux, David N; Awano, Tomoyuki; Engelstad, Kristin M; Sanchez-Quintero, Maria-Jose; Yang, Hong; Li, Fanghua; Li, Huapeng; Su, Qin; Shetler, Kara E; Jones, Lynne; Seo, Ryan; McConathy, Jonathan; Hillman, Elizabeth M; Noebels, Jeffrey L; De Vivo, Darryl C; Monani, Umrao R

    2017-01-20

    Haploinsufficiency of the SLC2A1 gene and paucity of its translated product, the glucose transporter-1 (Glut1) protein, disrupt brain function and cause the neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). There is little to suggest how reduced Glut1 causes cognitive dysfunction and no optimal treatment for Glut1 DS. We used model mice to demonstrate that low Glut1 protein arrests cerebral angiogenesis, resulting in a profound diminution of the brain microvasculature without compromising the blood-brain barrier. Studies to define the temporal requirements for Glut1 reveal that pre-symptomatic, AAV9-mediated repletion of the protein averts brain microvasculature defects and prevents disease, whereas augmenting the protein late, during adulthood, is devoid of benefit. Still, treatment following symptom onset can be effective; Glut1 repletion in early-symptomatic mutants that have experienced sustained periods of low brain glucose nevertheless restores the cerebral microvasculature and ameliorates disease. Timely Glut1 repletion may thus constitute an effective treatment for Glut1 DS.

  2. Biochemical Activities of the Wiskott-Aldrich Syndrome Homology Region 2 Domains of Sarcomere Length Short (SALS) Protein.

    Science.gov (United States)

    Tóth, Mónika Ágnes; Majoros, Andrea Kinga; Vig, Andrea Teréz; Migh, Ede; Nyitrai, Miklós; Mihály, József; Bugyi, Beáta

    2016-01-01

    Drosophila melanogaster sarcomere length short (SALS) is a recently identified Wiskott-Aldrich syndrome protein homology 2 (WH2) domain protein involved in skeletal muscle thin filament regulation. SALS was shown to be important for the establishment of the proper length and organization of sarcomeric actin filaments. Here, we present the first detailed characterization of the biochemical activities of the tandem WH2 domains of SALS (SALS-WH2). Our results revealed that SALS-WH2 binds both monomeric and filamentous actin and shifts the monomer-filament equilibrium toward the monomeric actin. In addition, SALS-WH2 can bind to but fails to depolymerize phalloidin- or jasplakinolide-bound actin filaments. These interactions endow SALS-WH2 with the following two major activities in the regulation of actin dynamics: SALS-WH2 sequesters actin monomers into non-polymerizable complexes and enhances actin filament disassembly by severing, which is modulated by tropomyosin. We also show that profilin does not influence the activities of the WH2 domains of SALS in actin dynamics. In conclusion, the tandem WH2 domains of SALS are multifunctional regulators of actin dynamics. Our findings suggest that the activities of the WH2 domains do not reconstitute the presumed biological function of the full-length protein. Consequently, the interactions of the WH2 domains of SALS with actin must be tuned in the cellular context by other modules of the protein and/or sarcomeric components for its proper functioning.

  3. The nonstructural protein 1 papain-like cysteine protease was necessary for porcine reproductive and respiratory syndrome virus nonstructural protein 1 to inhibit interferon-β induction.

    Science.gov (United States)

    Shi, Xibao; Zhang, Gaiping; Wang, Li; Li, Xuewu; Zhi, Yubao; Wang, Fangyu; Fan, Jianming; Deng, Ruiguang

    2011-06-01

    Porcine reproductive and respiratory syndrome virus nonstructural protein 1 (nsp1) could be auto-cleaved into nsp1α and nsp1β, both of which had the papain-like cysteine protease activities. Previous studies have shown that porcine reproductive and respiratory syndrome virus nsp1 was an interferon (IFN) antagonist. However, the mechanism by which nsp1 inhibited IFN-β production was unclear. Here, we used site-directed mutagenesis that inactivated the papain-like cysteine protease activities of nsp1 to explore whether the papain-like cysteine protease activities were required for nsp1 to disrupt IFN-β production. The results showed that mutations that inactivated papain-like cysteine protease activity of nsp1α made nsp1 lose its IFN antagonism activity, whereas mutations that inactivated papain-like cysteine protease activity of nsp1β did not influence the IFN antagonism activity of nsp1. In conclusion, our present work indicated that the papain-like cysteine protease activity of nsp1α was necessary for nsp1 to inhibit IFN-β induction.

  4. Increased adipose tissue secretion of Fetuin-A, lipopolysaccharide-binding protein and high-mobility group box protein 1 in metabolic syndrome.

    Science.gov (United States)

    Jialal, Ishwarlal; Devaraj, Sridevi; Bettaieb, Ahmed; Haj, Fawaz; Adams-Huet, Beverley

    2015-07-01

    Adipose Tissue (AT) dysregulation contributes to the pro-inflammatory state and insulin resistance of Metabolic Syndrome (MetS). We examined AT secretion of the hepatokine, Fetuin-A, LBP, sCD14 and HMGB-1, and toll-like receptor 2 and 4 protein levels in MetS and controls. Secreted levels of Fetuin-A, LBP, HMGB-1 and sCD14 and TLR2 and TLR4 protein in AT of controls and MetS patients were assayed. Also mRNA and protein for Fetuin-A, LBP, sCD14 and HMGB-1 were studied in subcutaneous fat depot of mice and during adipocyte differentiation. Secretion of Fetuin-A, LBP and HMGB-1 from AT were significantly increased in MetS (n = 28) compared to controls (n = 25), even after adjustment for adiposity. There were no significant differences in sCD14. Both LBP and Fetuin-A correlated significantly with HOMA-IR and increased significantly with increasing features of MetS. There was a significant increase in AT TLR2 and TLR4 protein in MetS compared to controls. Expression of Fetuin-A and LBP were significantly higher in subcutaneous white adipose tissue of HFD fed mice as well as in ob/ob mice compared to C57BL6/J control mice (n = 6 per group). Additionally mRNA and protein levels of FetA, LBP and HMGB-1 increased during differentiation of 3T3-L1 adipocytes. We make the novel observation of increased secretion of Fetuin A, LBP and HMGB-1 from AT and hypothesize that these engage TLRs in AT and other tissues contributing to the pro-inflammatory state and insulin resistance of MetS. Published by Elsevier Ireland Ltd.

  5. Protein levels of genes encoded on chromosome 21 in fetal Down Syndrome brain (Part V): overexpression of phosphatidyl-inositol-glycan class P protein (DSCR5).

    Science.gov (United States)

    Ferrando-Miguel, R; Cheon, M S; Lubec, G

    2004-06-01

    Down Syndrome (DS, trisomy 21) is the most common genetic cause of mental retardation. The completed sequencing of genes encoded on chromosome 21 provides excellent basic information, however the molecular mechanisms leading to the phenotype of DS remain to be elucidated. Although overexpression of chromosome 21 encoded genes has been documented information at the protein expression level is mandatory as it is the proteins that carry out function. We therefore decided to evaluated expression level of seven proteins whose genes are encoded on chromosome 21: DSCR4, DSCR5, DSCR6; KIR4.2, GIRK2, KCNE1 and KCNE2 in fetal cortex brain of DS and controls at the early second trimester of pregnancy by Western blotting. beta-actin and neuron specific enolase (NSE) were used to normalise cell loss and neuronal loss. DSCR5 (PIG-P), a component of glycosylphosphatidylinositol- N-acetylglucosaminyltransferase (GPI-GnT), was overexpressed about twofold, even when levels were normalised with NSE. DSCR6 was overexpressed in addition but when normalised versus NSE, levels were comparable to controls. DSCR4 was not detectable in fetal brain. Potassium channels KIR4.2 and GIRK2 were comparable between DS and controls, whereas KCNE1 and KCNE2 were not detectable. Quantification of these proteins encoded on chromosome 21 revealed that not all gene products of the DS critical region are overexpressed in DS brain early in life, indicating that the DS phenotype cannot be simply explained by the gene dosage effect hypothesis. Overexpression of PIG-P (DSCR5) may lead to or represent impaired glycosylphosphatidylinositol- N-acetylglucosaminyltransferase mediated posttranslational modifications and subsequent anchoring of proteins to the plasma membrane.

  6. Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of Meier-Gorlin syndrome.

    Directory of Open Access Journals (Sweden)

    Tom Stiff

    Full Text Available Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS, a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency.

  7. Expression of intestinal mucosa tight junctions claudin proteins and mRNA in patients with irritable bowel syndrome

    Institute of Scientific and Technical Information of China (English)

    KONG Wu-ming; GONG Jun; DONG Lei; LU Xiao-lan; XU Jun-rong

    2007-01-01

    Objective:To investigate the changes of intestinal mucosa tight junctions(TJs)claudin-1,-3,-4 proteins and mRNA changes in patients with irritable bowel syndrome(IBS)and to elucidate their possible roles in the changes of bowel evacuation habit and formation.Methods:Claudin-1,-3,-4 proteins and mRNA were evaluated in intestinal mucosa in control group,D-IBS(diarrhea IBS)group and C-IBS (constipation IBS)group with immunohistochemical assay and Realtime-PCR.Results:It was observed that claudin-1,-3,-4 proteins were localized in the membranes of epithelial cells along the entire length of the plasma membrane including the apical end of the epithelial cells.The claudins were concentrated at the site of TJs only.Claudin-1,-3,-4 mRNA and claudin-1 protein in small intestinal mucosa and colonal mucous in D-IBS group were significantly downregulated(P<0.05).Claudin-1,-3,-4 mRNA and proteins in small intestinal mucosa and co1onal mucous in C-IBS group were significantly upregulated(P<0.05).There was no significant difference in the expression of claudin-3 protein in both small intestinal mucosa and colonal mucous between D-IBS group and control group(P>0.05).Similarly,no significantly different expression of claudin-4 protein in colonal mucous in D-IBS group was found compared with control group(P>0.05).Otherwise,the expression of claudin-4 protein in small intestinal mucosa decreased in D-IBS group(P<0.05).Conclusion:Claudin-1,-3,-4 may play a potential important role in the changes of bowel evacuation habit and formation in patients with IBS.It is not due to the localization changes of claudin proteins in TJ,but may be caused by the quantitative changes of the expression of TJ proteins and mRNA.

  8. Serum tau protein as a marker of disease activity in enterohemorrhagic Escherichia coli O111-induced hemolytic uremic syndrome.

    Science.gov (United States)

    Kuroda, Mondo; Shimizu, Masaki; Inoue, Natsumi; Ikeno, Iku; Nakagawa, Hiroyasu; Yokoi, Ayano; Niida, Yo; Konishi, Michio; Kaneda, Hisashi; Igarashi, Noboru; Yamahana, Junya; Taneichi, Hiromichi; Kanegane, Hirokazu; Ito, Mika; Saito, Shigeru; Furuichi, Kengo; Wada, Takashi; Nakagawa, Masaru; Yokoyama, Hitoshi; Yachie, Akihiro

    2015-01-01

    Tau protein levels in cerebrospinal fluid (CSF) and serum are elevated in patients with various central nervous system diseases. We investigated whether serum tau protein levels are useful for predicting and assessing disease activity of acute encephalopathy (AE) in enterohemorrhagic Escherichia coli (EHEC) O111-induced hemolytic uremic syndrome (HUS; EHEC encephalopathy). Serum samples were obtained from 14 patients with EHEC O111/HUS, 20 patients with non-EHEC-related AE, and 20 age- and sex-matched healthy controls. CSF samples were obtained from 2 patients with EHEC encephalopathy and 20 patients with non-EHEC-related AE. Tau protein levels and levels of several proinflammatory cytokines were quantified by enzyme-linked immunosorbent assays. Results were compared with the clinical features of EHEC encephalopathy, including magnetic resonance image (MRI) findings. Serum tau levels in patients with EHEC encephalopathy were significantly elevated compared with those in patients with EHEC O111/HUS without encephalopathy, patients with non-EHEC-related AE, and healthy controls. The ratio of CSF tau levels to serum tau levels was >1.0 in all patients with non-EHEC-related AE but encephalopathy. Serum tau protein levels increased rapidly and markedly in patients with severe EHEC 0111/HUS and encephalopathy when HUS occurred, but were not elevated in mild patients, even in the HUS phase. Furthermore, changes in serum tau protein levels in patients with EHEC encephalopathy were consistent with abnormalities on brain MRI and were positively correlated with proinflammatory cytokine levels. Our results indicate that serum tau protein might be useful to predict and assess disease activity of EHEC encephalopathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Effects of Soy-Germ Protein on Catalase Activity of Plasma and Erythocyte of Metabolic Syndrome Women

    Directory of Open Access Journals (Sweden)

    Hery Winarsi

    2015-01-01

    Full Text Available Oxidative stress always accompany patients with metabolic syndrome (MS. Several researchers reported that soy-protein is able to decrease oxidative stress level. However, there is no report so far about soy-germ protein in relation to its potential to the decrease oxidative stress level of MS patients. The aim of this study was to explore the potential of soy-germ protein on activity of catalase enzyme in blood’s plasma as well as erythrocytes of MS patients. Double-blind randomized clinical trial was used as an experimental study. Thirty respondents were included in this study with MS, normal level blood sugar, low-HDL cholesterol but high in triglyceride, 40-65 years old, Body Mass Index > 25 kg/m2, live in Purwokerto and agreed to sign the informed consent. They were randomly grouped into 3 different groups, 10 each: Group I, was given special milk that contains soy-germ protein and Zn; Group II, soy-germ protein, while Group III was placebo; for two consecutive months. Data were taken from blood samples in 3 different periods i.e. 0, 1, and 2 months after treatment. Two months after treatment, there was an increase from 5.36 to 20.17 IU/mg (P = 0.028 in activity of catalase enzyme in blood’s plasma respondents who consumed milk containing soy-germ protein with or without Zn. A similar trend of catalase activity, but at a lower level, was also noticed in erythrocyte; which increased from 88.31 to 201.11 IU/mg (P = 0.013. The increase in activity of catalase enzyme in blood’s plasma was 2.2 times higher than that in erythrocytes.

  10. Roles of viroplasm-like structures formed by nonstructural protein NSs in infection with severe fever with thrombocytopenia syndrome virus.

    Science.gov (United States)

    Wu, Xiaodong; Qi, Xian; Liang, Mifang; Li, Chuan; Cardona, Carol J; Li, Dexin; Xing, Zheng

    2014-06-01

    Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging bunyavirus that causes a hemorrhagic fever with a high mortality rate. The virus is likely tick-borne and replicates primarily in hemopoietic cells, which may lead to disregulation of proinflammatory cytokine induction and loss of leukocytes and platelets. The viral genome contains L, M, and S segments encoding a viral RNA polymerase, glycoproteins G(n) and G(c), nucleoprotein (NP), and a nonstructural S segment (NSs) protein. NSs protein is involved in the regulation of host innate immune responses and suppression of IFNβ-promoter activities. In this article, we demonstrate that NSs protein can form viroplasm-like structures (VLSs) in infected and transfected cells. NSs protein molecules interact with one another, interact with NP, and were associated with viral RNA in infected cells, suggesting that NSs protein may be involved in viral replication. Furthermore, we observed that NSs-formed VLS colocalized with lipid droplets and that inhibitors of fatty acid biosynthesis decreased VLS formation or viral replication in transfected and infected cells. Finally, we have demonstrated that viral dsRNAs were also localized in VLS in infected cells, suggesting that NSs-formed VLS may be implicated in the replication of SFTS bunyavirus. These findings identify a novel function of nonstructural NSs in SFTSV-infected cells where it is a scaffolding component in a VLS functioning as a virus replication factory. This function is in addition to the role of NSs protein in modulating host responses that will broaden our understanding of viral pathogenesis of phleboviruses.

  11. Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization.

    OpenAIRE

    2012-01-01

    Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epid...

  12. Hydrodynamic control of microphytoplankton bloom in a coastal sea

    Science.gov (United States)

    Murty, K. Narasimha; Sarma, Nittala S.; Pandi, Sudarsana Rao; Chiranjeevulu, Gundala; Kiran, Rayaprolu; Muralikrishna, R.

    2017-08-01

    The influence of hydrodynamics on phytoplankton bloom occurrence/formation has not been adequately reported. Here, we document diurnal observations in the tropical Bay of Bengal's mid-western shelf region which reveal microphytoplankton cell density maxima in association with neap tide many times more than what could be accounted for by solar insolation and nutrient levels. When in summer, phytoplankton cells were abundant and the cell density of Guinardia delicatula reached critical value by tide caused zonation, aggregation happened to an intense bloom. Mucilaginous exudates from the alga due to heat and silicate stress likely promoted and stable water column and weak winds left undisturbed, the transient bloom. The phytoplankton aggregates have implication as food resource in the benthic region implying higher fishery potential, in carbon dioxide sequestration (carbon burial) and in efforts towards improving remote sensing algorithms for chlorophyll in the coastal region.

  13. Hydrodynamic control of microphytoplankton bloom in a coastal sea

    Indian Academy of Sciences (India)

    K Narasimha Murty; Nittala S Sarma; Sudarsana Rao Pandi; Gundala Chiranjeevulu; Rayaprolu Kiran; R Muralikrishna

    2017-08-01

    The influence of hydrodynamics on phytoplankton bloom occurrence/formation has not been adequately reported. Here, we document diurnal observations in the tropical Bay of Bengal’s mid-western shelf region which reveal microphytoplankton cell density maxima in association with neap tide many times more than what could be accounted for by solar insolation and nutrient levels. When in summer, phytoplankton cells were abundant and the cell density of Guinardia delicatula reached critical value by tide caused zonation, aggregation happened to an intense bloom. Mucilaginous exudates from the alga due to heat and silicate stress likely promoted and stable water column and weak winds left undisturbed, the transient bloom. The phytoplankton aggregates have implication as food resource in the benthic region implying higher fishery potential, in carbon dioxide sequestration (carbon burial) and in efforts towards improving remote sensing algorithms for chlorophyll in the coastal region.

  14. Harmful Algal Bloom in Iligan Bay, Southern Philippines

    Directory of Open Access Journals (Sweden)

    Helen J Vicente

    2002-12-01

    Full Text Available We report the first occurrence of harmful algal bloom (HAB caused by a non-toxic dinoflagellate, Cochlodinium sp. in Philippine waters, particularly, in Kalangahan Pt.-Manticao Pt., Iligan Bay on March 13-18, 2002. Two patches of Cochlodinium sp. bloom, associated with fish kills in Kalangahan Pt.-Mantacao Pt., Iligan Bay, caused localized water discoloration from the usual ocean blue to rusty brown or reddish brown to blackish. The first patch, located near fish-aggregating device (FAD areas, spanned 2 km wide, while the second patch, located near a fish corral, spanned 500m wide. These patches occupied the water column from surface to 5 m depth, but a thick mat formed at 0.5 m to surface. Patches occupied the water column from surface to 5 m depth, but a thick mat formed at 0.5 m to surface. Patches decreased as the bloom began to decline. The observed dead demersal and pelagic fishes coincided with highest bloom density of 3.1 x 104 to 3.8 x 104 cells ml-1 of Cochlodinium. Dissected gills and stomach contents of fishes killed in HAB-affected areas did not reveal any indication of clogging of gills by Cochlodinium sp. Fishes covered by the “shading effect” of Cochlodinium bloom may have suffered anoxia or asphyxation due to oxygen depletion. No poisoning of people who consumed the dead fishes was reported. Laboratory analyses revealed lower DO values, 2.4 to 0.5 mg L-1from 2400 to 0600Hr; 14N:1P ratio; air-water temperature ranged from 28-29°C; pH 7.89-8.29; and salinity, 33-35°/oo. Favella sp., a tintinnid grazer of dinoflagellate was developing in the area at the termination of the Cochlodinium bloom on March 18.

  15. A novel single-parameter approach for forecasting algal blooms.

    Science.gov (United States)

    Xiao, Xi; He, Junyu; Huang, Haomin; Miller, Todd R; Christakos, George; Reichwaldt, Elke S; Ghadouani, Anas; Lin, Shengpan; Xu, Xinhua; Shi, Jiyan

    2017-01-01

    Harmful algal blooms frequently occur globally, and forecasting could constitute an essential proactive strategy for bloom control. To decrease the cost of aquatic environmental monitoring and increase the accuracy of bloom forecasting, a novel single-parameter approach combining wavelet analysis with artificial neural networks (WNN) was developed and verified based on daily online monitoring datasets of algal density in the Siling Reservoir, China and Lake Winnebago, U.S.A. Firstly, a detailed modeling process was illustrated using the forecasting of cyanobacterial cell density in the Chinese reservoir as an example. Three WNN models occupying various prediction time intervals were optimized through model training using an early stopped training approach. All models performed well in fitting historical data and predicting the dynamics of cyanobacterial cell density, with the best model predicting cyanobacteria density one-day ahead (r = 0.986 and mean absolute error = 0.103 × 10(4) cells mL(-1)). Secondly, the potential of this novel approach was further confirmed by the precise predictions of algal biomass dynamics measured as chl a in both study sites, demonstrating its high performance in forecasting algal blooms, including cyanobacteria as well as other blooming species. Thirdly, the WNN model was compared to current algal forecasting methods (i.e. artificial neural networks, autoregressive integrated moving average model), and was found to be more accurate. In addition, the application of this novel single-parameter approach is cost effective as it requires only a buoy-mounted fluorescent probe, which is merely a fraction (∼15%) of the cost of a typical auto-monitoring system. As such, the newly developed approach presents a promising and cost-effective tool for the future prediction and management of harmful algal blooms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Intense blooms of Trichodesmium erythraeum (Cyanophyta) in the open waters along east coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Jyothibabu, R.; Madhu, N.V.; Murukesh, N.; Haridas, P.; Nair, K.K.C.; Venugopal, P.

    -1) was obtained in these regions, which indicated the enhancement of primary production in the earlier stages of the bloom. Very low NO3-N concentrations, brownish yellow bloom colour, undisturbed patches and high primary production strongly...

  17. Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity

    DEFF Research Database (Denmark)

    Belling, Kirstine González-Izarzugaza; Russo, Francesco; Jensen, Anders Boeck

    2017-01-01

    Jak-STAT pathway, dysregulated genes important for disturbed immune system (IL4), energy balance (POMC and LEP) and erythropoietin signalling in KS. We present an extended epidemiological study that links KS comorbidities to the molecular level and identify potential causal players in the disease...... of co-expressed modules as well as central hubs and gene dosage perturbed protein complexes in a KS comorbidity network build from known disease proteins and their protein-protein interactions. The systems biology approaches together pointed to novel aspects of KS disease phenotypes including perturbed...

  18. Marine harmful algal blooms, human health and wellbeing

    DEFF Research Database (Denmark)

    Berdalet, Elisa; Fleming, Lora E.; Gowen, Richard

    2016-01-01

    Microalgal blooms are a natural part of the seasonal cycle of photosynthetic organisms in marine ecosystems. They are key components of the structure and dynamics of the oceans and thus sustain the benefits that humans obtain from these aquatic environments. However, some microalgal blooms can...... maintaining intensive, multidisciplinary and collaborative scientific research, and strengthening the coordination with stakeholders, policymakers and the general public. Here we provide an overview of different aspects of the HABs phenomena, an important element of the intrinsic links between oceans...

  19. [Causes of jellyfish blooms and their influence on marine environment].

    Science.gov (United States)

    Qu, Chang-feng; Song, Jin-ming; Li, Ning

    2014-12-01

    Jellyfish blooms have damaged the normal composition and function of marine ecosystem and ecological environments, which have been one of the new marine ecological disasters. In this study, we summarized the possible inducements of jellyfish blooms, and the influences of jellyfish blooms on biogenic elements, dissolved oxygen, seawater acidity and biological community were discussed emphatically. The results showed that jellyfish blooms had a close contact with its physiological structure and life history, which had favorable characteristics including simple body struc- ture, rapid growth, thriving reproduction and short generation interval to tolerate harsh environment better. Jellyfish abundance increased rapidly when it encountered suitable conditions. The temperature variations of seawater might be the major inducing factor which could result in jellyfish blooms. Jellyfish blooms may benefit from warmer temperature that could increase the food availability of jellyfish and promote jellyfish reproduction, especially for warm temperate jellyfish species. Eutrophication, climate change, overfishing, alien invasions and habitat modification were all possible important contributory factors of jellyfish blooms. Jellyfish could significantly influence the form distribution and biogeochemical cycling of biogenic elements. Jellyfish excreted NH4+ and P04(3-) at a rate of 59.1-91.5 micromol N x kg(-1) x h(-1) and 1.1-1.8 micromol P x kg(-1) x h(-1), which could meet about 8%-10% and 21.6% of the phytoplankton primary production requirement of N and P, respectively. Live jellyfish released dissolved organic carbon (DOC) at a rate of 1.0 micromol C x g(-1) x d(-1). As jellyfish decomposing, the effluxes of total N and total P were 4000 micromol N x kg(-1) x d(-1) and 120 micromol P x kg(-1) x d(-1), respectively, while the efflux of DOC reached 30 micromol C x g(-1) x d(-1). Jellyfish decomposition could cause seawater acidification and lowered level of dissolved oxygen

  20. The cognitive context of examinations in psychiatry using Bloom's taxonomy.

    Science.gov (United States)

    Miller, D A; Sadler, J Z; Mohl, P C; Melchiode, G A

    1991-11-01

    Psychiatric practice involves complex thinking patterns. In addition to commanding a huge number of facts, the student must learn to manipulate factual knowledge to solve diagnostic problems, develop treatment plans, and critically evaluate those plans. This study demonstrates an empirical method for evaluating the level of cognitive processes tested in multiple choice examinations. Use of Bloom's taxonomy in evaluating test items demonstrated the majority of test items on a psychiatry clerkship examination and a resident in-training examination fell into the most basic cognitive level, that of simple recall. The utility of Bloom's taxonomy is discussed along with implications for medical education.

  1. Improving retouched Bloom filter for trading off selected false positives against false negatives

    OpenAIRE

    Donnet, Benoît; Baynat, Bruno; Friedman, Timur

    2010-01-01

    Where distributed agents must share voluminous set membership information, Bloom fil- ters provide a compact, though lossy, way for them to do so. Numerous recent networking papers have examined the trade-offs between the bandwidth consumed by the transmis- sion of Bloom filters, and the error rate, which takes the form of false positives. This paper is about the retouched Bloom filter (RBF). An RBF is an extension that makes the Bloom fil- ter more flexible by permitting the removal of false...

  2. Retouched Bloom Filters: Allowing Networked Applications to Flexibly Trade Off False Positives Against False Negatives

    OpenAIRE

    Donnet, Benoît; Baynat, Bruno; Friedman, Timur

    2006-01-01

    Where distributed agents must share voluminous set mem- bership information, Bloom filters provide a compact, though lossy, way for them to do so. Numerous recent networking papers have examined the trade-offs between the bandwidth consumed by the transmission of Bloom filters, and the er- ror rate, which takes the form of false positives, and which rises the more the filters are compressed. In this paper, we introduce the retouched Bloom filter (RBF), an extension that makes the Bloom filter...

  3. Atherosclerosis in ancient humans, accelerated aging syndromes and normal aging: is lamin a protein a common link?

    Science.gov (United States)

    Miyamoto, Michael I; Djabali, Karima; Gordon, Leslie B

    2014-06-01

    Imaging studies of ancient human mummies have demonstrated the presence of vascular calcification that is consistent with the presence of atherosclerosis. These findings have stimulated interest in the underlying biological processes that might impart to humans an inherent predisposition to the development of atherosclerosis. Clues to these processes may possibly be found in accelerated aging syndromes, such as Hutchinson-Gilford progeria syndrome (HGPS), an ultra-rare disorder characterized by premature aging phenotypes, including very aggressive forms of atherosclerosis, occurring in childhood. The genetic defect in HGPS eventuates in the production of a mutant form of the nuclear structural protein lamin A, called progerin, which is thought to interfere with normal nuclear functioning. Progerin appears to be expressed in vascular cells, resulting in vessel wall cell loss and replacement by fibrous tissue, reducing vessel compliance and promoting calcification, leading to the vascular dysfunction and atherosclerosis seen in HGPS. Interestingly, vascular progerin is detectable in lower levels, in an age-related manner, in the general population, providing the basis for further study of the potential role of abnormal forms of lamin A in the atherosclerotic process of normal aging.

  4. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2.

    Science.gov (United States)

    Amr, Sami; Heisey, Cindy; Zhang, Min; Xia, Xia-Juan; Shows, Kathryn H; Ajlouni, Kamel; Pandya, Arti; Satin, Leslie S; El-Shanti, Hatem; Shiang, Rita

    2007-10-01

    A single missense mutation was identified in a novel, highly conserved zinc-finger gene, ZCD2, in three consanguineous families of Jordanian descent with Wolfram syndrome (WFS). It had been shown that these families did not have mutations in the WFS1 gene (WFS1) but were mapped to the WFS2 locus at 4q22-25. A G-->C transversion at nucleotide 109 predicts an amino acid change from glutamic acid to glutamine (E37Q). Although the amino acid is conserved and the mutation is nonsynonymous, the pathogenesis for the disorder is because the mutation also causes aberrant splicing. The mutation was found to disrupt messenger RNA splicing by eliminating exon 2, and it results in the introduction of a premature stop codon. Mutations in WFS1 have also been found to cause low-frequency nonsyndromic hearing loss, progressive hearing loss, and isolated optic atrophy associated with hearing loss. Screening of 377 probands with hearing loss did not identify mutations in the WFS2 gene. The WFS1-encoded protein, Wolframin, is known to localize to the endoplasmic reticulum and plays a role in calcium homeostasis. The ZCD2-encoded protein, ERIS (endoplasmic reticulum intermembrane small protein), is also shown to localize to the endoplasmic reticulum but does not interact directly with Wolframin. Lymphoblastoid cells from affected individuals show a significantly greater rise in intracellular calcium when stimulated with thapsigargin, compared with controls, although no difference was observed in resting concentrations of intracellular calcium.

  5. Telomeric protein TRF2 protects Holliday junctions with telomeric arms from displacement by the Werner syndrome helicase.

    Science.gov (United States)

    Nora, Gerald J; Buncher, Noah A; Opresko, Patricia L

    2010-07-01

    WRN protein loss causes Werner syndrome (WS), which is characterized by premature aging as well as genomic and telomeric instability. WRN prevents telomere loss, but the telomeric protein complex must regulate WRN activities to prevent aberrant telomere processing. Telomere-binding TRF2 protein inhibits telomere t-loop deletion by blocking Holliday junction (HJ) resolvase cleavage activity, but whether TRF2 also modulates HJ displacement at t-loops is unknown. In this study, we used multiplex fluorophore imaging to track the fate of individual strands of HJ substrates. We report the novel finding that TRF2 inhibits WRN helicase strand displacement of HJs with telomeric repeats in duplex arms, but unwinding of HJs with a telomeric center or lacking telomeric sequence is unaffected. These data, together with results using TRF2 fragments and TRF2 HJ binding assays, indicate that both the TRF2 B- and Myb domains are required to inhibit WRN HJ activity. We propose a novel model whereby simultaneous binding of the TRF2 B-domain to the HJ core and the Myb domain to telomeric arms promote and stabilize HJs in a stacked arm conformation that is unfavorable for unwinding. Our biochemical study provides a mechanistic basis for the cellular findings that TRF2 regulates WRN activity at telomeres.

  6. Metabolic manifestations of polycystic ovary syndrome in nonobese adolescents: retinol-binding protein 4 and ectopic fat deposition

    Science.gov (United States)

    Sopher, Aviva B.; Gerken, Adrienne T.; Blaner, William S.; Root, Jeremy M.; McMahon, Donald J.; Oberfield, Sharon E.

    2013-01-01

    Objective To determine whether nonobese adolescents with polycystic ovary syndrome (PCOS) have higher levels of retinol-binding protein 4 (RBP4) and ectopic fat than controls and whether RBP4 and ectopic fat correlate with comorbidities of metabolic disease. Design Cross-sectional case-control study. Setting Pediatric clinical research center based in a quaternary care medical center. Patient(s) Twenty-four nonobese adolescents between the ages of 13 and 21 years, 13 with PCOS and 11 controls. Intervention(s) Measurement of RBP4, insulin resistance, lipids, and body composition. Main Outcome Measure(s) Retinol-binding protein 4, reproductive and adrenal hormones, insulin resistance, intrahepatic and intramyocellular lipid levels, and visceral adipose tissue. Result(s) Adolescents with PCOS had higher intrahepatic lipid content and a statistical trend for higher RBP4 compared with controls. Retinol-binding protein 4 correlated with body fat, triglycerides, insulin resistance, and androgens but not intrahepatic lipid content; however, when adjusted for body fat, the correlation between RBP4 and triglycerides weakened to a statistical trend and was no longer statistically significant for the other measures. Conclusion(s) This small preliminary study of nonobese adolescent girls suggests that RBP4 may be involved in the dyslipidemia associated with PCOS and that there may be an independent relationship between RBP4 and triglycerides but not between RBP4 and insulin resistance. Although intrahepatic lipid content was higher in PCOS, it did not correlate with RBP4, triglycerides, or insulin resistance. PMID:22341881

  7. Genes Related to Mitochondrial Functions, Protein Degradation, and Chromatin Folding Are Differentially Expressed in Lymphomonocytes of Rett Syndrome Patients

    Science.gov (United States)

    Leoni, Guido; Cervellati, Franco; Canali, Raffaella; Cortelazzo, Alessio; De Felice, Claudio; Ciccoli, Lucia; Hayek, Joussef

    2013-01-01

    Rett syndrome (RTT) is mainly caused by mutations in the X-linked methyl-CpG binding protein (MeCP2) gene. By binding to methylated promoters on CpG islands, MeCP2 protein is able to modulate several genes and important cellular pathways. Therefore, mutations in MeCP2 can seriously affect the cellular phenotype. Today, the pathways that MeCP2 mutations are able to affect in RTT are not clear yet. The aim of our study was to investigate the gene expression profiles in peripheral blood lymphomonocytes (PBMC) isolated from RTT patients to try to evidence new genes and new pathways that are involved in RTT pathophysiology. LIMMA (Linear Models for MicroArray) and SAM (Significance Analysis of Microarrays) analyses on microarray data from 12 RTT patients and 7 control subjects identified 482 genes modulated in RTT, of which 430 were upregulated and 52 were downregulated. Functional clustering of a total of 146 genes in RTT identified key biological pathways related to mitochondrial function and organization, cellular ubiquitination and proteosome degradation, RNA processing, and chromatin folding. Our microarray data reveal an overexpression of genes involved in ATP synthesis suggesting altered energy requirement that parallels with increased activities of protein degradation. In conclusion, these findings suggest that mitochondrial-ATP-proteasome functions are likely to be involved in RTT clinical features. PMID:24453408

  8. Genes Related to Mitochondrial Functions, Protein Degradation, and Chromatin Folding Are Differentially Expressed in Lymphomonocytes of Rett Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Alessandra Pecorelli

    2013-01-01

    Full Text Available Rett syndrome (RTT is mainly caused by mutations in the X-linked methyl-CpG binding protein (MeCP2 gene. By binding to methylated promoters on CpG islands, MeCP2 protein is able to modulate several genes and important cellular pathways. Therefore, mutations in MeCP2 can seriously affect the cellular phenotype. Today, the pathways that MeCP2 mutations are able to affect in RTT are not clear yet. The aim of our study was to investigate the gene expression profiles in peripheral blood lymphomonocytes (PBMC isolated from RTT patients to try to evidence new genes and new pathways that are involved in RTT pathophysiology. LIMMA (Linear Models for MicroArray and SAM (Significance Analysis of Microarrays analyses on microarray data from 12 RTT patients and 7 control subjects identified 482 genes modulated in RTT, of which 430 were upregulated and 52 were downregulated. Functional clustering of a total of 146 genes in RTT identified key biological pathways related to mitochondrial function and organization, cellular ubiquitination and proteosome degradation, RNA processing, and chromatin folding. Our microarray data reveal an overexpression of genes involved in ATP synthesis suggesting altered energy requirement that parallels with increased activities of protein degradation. In conclusion, these findings suggest that mitochondrial-ATP-proteasome functions are likely to be involved in RTT clinical features.

  9. Low heart-type fatty acid binding protein level during aging may protect down syndrome people against atherosclerosis

    Directory of Open Access Journals (Sweden)

    Vianello Elena

    2013-01-01

    Full Text Available Abstract Background Aging is considered an important independent risk factor for atherosclerosis. Down syndrome people (DS display an accelerated aging process compared to healthy subjects, anyway they are relatively resistant to developing atherosclerosis. The mechanisms involved in such protective effect are not well known. Since heart-type fatty acid binding protein (H-FABP is a protein involved in the transport of fatty acids and it has been recently correlated with the presence of atherosclerosis, we aimed to measure H-FABP level both in DS and in healthy subjects during aging to evaluate the association between this molecule, aging and atherosclerosis. Findings We quantified plasmatic H-FABP level in three groups of male DS and age-matched healthy subjects (children, age 2–14 years; adults, age 20–50 years; elderly, > 60 years using a biochip array analyzer. We observed that aging is associated with increased H-FABP level in healthy subjects but not in DS which display both the same protein level in the different ages of life and have also lower level compared to their age-matched healthy subjects. Conclusion Reduced H-FABP level during aging in DS may play a protective role against atherosclerosis. The potential involvement of H-FABP in the relationship between aging, atherosclerosis and development of coronary artery disease needs further investigations.

  10. MOLECULAR DOCKING ANALYSES OF CYNODON DACTYLON DERIVED PHYTOCHEMICALS AGAINST WHITE SPOT SYNDROME VIRUS (WSSV STRUCTURAL PROTEIN VP26

    Directory of Open Access Journals (Sweden)

    Damayanthi Devi.I

    2015-05-01

    Full Text Available White spot disease is a major infectious disease of penaeid shrimps caused by the white spot syndrome virus (WSSV. The viral structural proteins are responsib le for binding virus to the cellular membranes of the host that is being systematically infected. An In silic o attempt was made to identify the potential drug to inhibit the WSSV spread of diseases. For that an effort , was made to deduce the antiviral potentiality of Cynodon dactylon derived phytochemicals with docking tec hnique. To stimulate the structure based drug design the, 3D structure of the VP26 (PDB-ID: 2EDM, a tegument protein thought to be i nvolved in the entry of WSSV nucleocapsid into the host nucleus, is retrieved from PDB datab ase and docking studies are carried out with the sketched phytochemical structures using GOLD software. Among the phytochemicals scr eened, luteolin and apigenin shows the best binding affinity with binding energies of 42.51 and 38.92 K.cal/m ol exhibiting the potential to block VP26 (2EDM protein of WSSV. This study will be helpful in developing novel antiviral drugs from plant sources against aquatic important pathogens.

  11. Nuclear magnetic resonance structure of the nucleic acid-binding domain of severe acute respiratory syndrome coronavirus nonstructural protein 3.

    Science.gov (United States)

    Serrano, Pedro; Johnson, Margaret A; Chatterjee, Amarnath; Neuman, Benjamin W; Joseph, Jeremiah S; Buchmeier, Michael J; Kuhn, Peter; Wüthrich, Kurt

    2009-12-01

    The nuclear magnetic resonance (NMR) structure of a globular domain of residues 1071 to 1178 within the previously annotated nucleic acid-binding region (NAB) of severe acute respiratory syndrome coronavirus nonstructural protein 3 (nsp3) has been determined, and N- and C-terminally adjoining polypeptide segments of 37 and 25 residues, respectively, have been shown to form flexibly extended linkers to the preceding globular domain and to the following, as yet uncharacterized domain. This extension of the structural coverage of nsp3 was obtained from NMR studies with an nsp3 construct comprising residues 1066 to 1181 [nsp3(1066-1181)] and the constructs nsp3(1066-1203) and nsp3(1035-1181). A search of the protein structure database indicates that the globular domain of the NAB represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. Two antiparallel two-strand beta-sheets and two 3(10)-helices are anchored against the surface of this barrel-like molecular core. Chemical shift changes upon the addition of single-stranded RNAs (ssRNAs) identified a group of residues that form a positively charged patch on the protein surface as the binding site responsible for the previously reported affinity for nucleic acids. This binding site is similar to the ssRNA-binding site of the sterile alpha motif domain of the Saccharomyces cerevisiae Vts1p protein, although the two proteins do not share a common globular fold.

  12. Prohibitin Interacts with envelope proteins of white spot syndrome virus and prevents infection in the red swamp crayfish, Procambarus clarkii.

    Science.gov (United States)

    Lan, Jiang-Feng; Li, Xin-Cang; Sun, Jie-Jie; Gong, Jing; Wang, Xian-Wei; Shi, Xiu-Zhen; Shi, Li-Jie; Weng, Yu-Ding; Zhao, Xiao-Fan; Wang, Jin-Xing

    2013-12-01

    Prohibitins (PHBs) are ubiquitously expressed conserved proteins in eukaryotes that are associated with apoptosis, cancer formation, aging, stress responses, cell proliferation, and immune regulation. However, the function of PHBs in crustacean immunity remains largely unknown. In the present study, we identified a PHB in Procambarus clarkii red swamp crayfish, which was designated PcPHB1. PcPHB1 was widely distributed in several tissues, and its expression was significantly upregulated by white spot syndrome virus (WSSV) challenge at the mRNA level and the protein level. These observations prompted us to investigate the role of PcPHB1 in the crayfish antiviral response. Recombinant PcPHB1 (rPcPHB1) significantly reduced the amount of WSSV in crayfish and the mortality of WSSV-infected crayfish. The quantity of WSSV in PcPHB1 knockdown crayfish was increased compared with that in the controls. The effects of RNA silencing were rescued by rPcPHB1 reinjection. We further confirmed the interaction of PcPHB1 with the WSSV envelope proteins VP28, VP26, and VP24 using pulldown and far-Western overlay assays. Finally, we observed that the colloidal gold-labeled PcPHB1 was located on the outer surface of the WSSV, which suggests that PcPHB1 specifically binds to the envelope proteins of WSSV. VP28, VP26, and VP24 are structural envelope proteins and are essential for attachment and entry into crayfish cells. Therefore, PcPHB1 exerts its anti-WSSV effect by binding to VP28, VP26, and VP24, preventing viral infection. This study is the first report on the antiviral function of PHB in the innate immune system of crustaceans.

  13. Unraveling the molecular effects of mutation L270P on Wiskkot-Aldrich syndrome protein: insights from molecular dynamics approach.

    Science.gov (United States)

    Palaniappan, Chandrasekaran; Rao, Sethumadhavan; Ramalingam, Rajasekaran

    2016-09-01

    Missense mutation L270P disrupts the auto-inhibited state of "Wiskkot-Aldrich syndrome protein" (WASP), thereby constitutively activating the mutant structure, a key event for pathogenesis of X-linked neutropenia (XLN). In this study, we comprehensively deciphered the molecular feature of activated mutant structure by all atom molecular dynamics (MD) approach. MD analysis revealed that mutant structure exposed a wide variation in the spatial environment of atoms, resulting in enhanced residue flexibility. The increased flexibility of residues favored to decrease the number of intra-molecular hydrogen bonding interactions in mutant structure. The reduction of hydrogen bonds in the mutant structure resulted to disrupt the local folding of secondary structural elements that eventually affect the proper folding of mutants. The unfolded state of mutant structure established more number of inter-molecular hydrogen bonding interaction at interface level due to the conformational variability, thus mediated high binding affinity with its interacting partner, Cdc42.

  14. Identification of the interaction domains of white spot syndrome virus envelope proteins VP28 and VP24.

    Science.gov (United States)

    Li, Zaipeng; Chen, Weiyu; Xu, Limei; Li, Fang; Yang, Feng

    2015-03-16

    VP28 and VP24 are two major envelope proteins of white spot syndrome virus (WSSV). The direct interaction between VP28 and VP24 has been described in previous studies. In this study, we confirmed this interaction and mapped the interaction domains of VP28 and VP24 by constructing a series of deletion mutants. By co-immunoprecipitation, two VP28-binding domains of VP24 were located at amino acid residues 46-61 and 148-160, while VP24-binding domain of VP28 was located at amino acid residues 31-45. These binding domains were further corroborated by peptide blocking assay, in which synthetic peptides spanning the binding domains were able to inhibit VP28-VP24 interaction, whereas same-size control peptides from non-binging regions did not.

  15. Context discovery using attenuated Bloom filters in ad-hoc networks

    NARCIS (Netherlands)

    Liu, F.; Heijenk, Gerhard J.

    2007-01-01

    A novel approach to performing context discovery in ad-hoc networks based on the use of attenuated Bloom filters is proposed in this paper. A Bloom filter is an efficient spacesaving data structure to represent context information. Attenuated Bloom filters are used to advertise the availability of c

  16. Return bloom in 'Stayman' apple with NAA and/or ethephon: 2007 through 2009

    Science.gov (United States)

    Following a season in which apple trees produce a full crop, many cultivars fail to produce enough bloom the next year for an adequate crop. Obtaining good return bloom is a problem for many apple growers. Plant growth regulators (PGRs) are recommended to enhance return bloom in apple. This study...

  17. A Preliminary Bloom's Taxonomy Assessment of End-of-Chapter Problems in Business School Textbooks

    Science.gov (United States)

    Marshall, Jennings B.; Carson, Charles M.

    2008-01-01

    This article examines textbook problems used in a sampling of some of the most common core courses found in schools of business to ascertain what level of learning, as defined by Bloom's Taxonomy, is required to provide a correct answer. A set of working definitions based on Bloom's Taxonomy (Bloom & Krathwohl, 1956) was developed for the six…

  18. Characterisation of algal organic matter produced by bloom-forming marine and freshwater algae

    KAUST Repository

    Villacorte, Loreen O.

    2015-04-01

    Algal blooms can seriously affect the operation of water treatment processes including low pressure (micro- and ultra-filtration) and high pressure (nanofiltration and reverse osmosis) membranes mainly due to accumulation of algal-derived organic matter (AOM). In this study, the different components of AOM extracted from three common species of bloom-forming algae (Alexandrium tamarense, Chaetoceros affinis and Microcystis sp.) were characterised employing various analytical techniques, such as liquid chromatography - organic carbon detection, fluorescence spectroscopy, fourier transform infrared spectroscopy, alcian blue staining and lectin staining coupled with laser scanning microscopy to indentify its composition and force measurement using atomic force microscopy to measure its stickiness. Batch culture monitoring of the three algal species illustrated varying characteristics in terms of growth pattern, cell concentration and AOM release. The AOM produced by the three algal species comprised mainly biopolymers (e.g., polysaccharides and proteins) but some refractory compounds (e.g., humic-like substances) and other low molecular weight acid and neutral compounds were also found. Biopolymers containing fucose and sulphated functional groups were found in all AOM samples while the presence of other functional groups varied between different species. A large majority (>80%) of the acidic polysaccharide components (in terms of transparent exopolymer particles) were found in the colloidal size range (<0.4μm). The relative stickiness of AOM substantially varied between algal species and that the cohesion between AOM-coated surfaces was much stronger than the adhesion of AOM on AOM-free surfaces. Overall, the composition as well as the physico-chemical characteristics (e.g., stickiness) of AOM will likely dictate the severity of fouling in membrane systems during algal blooms.

  19. C-reactive protein, high-molecular-weight adiponectin and development of metabolic syndrome in the Japanese general population: a longitudinal cohort study.

    Directory of Open Access Journals (Sweden)

    Yoshifumi Saisho

    Full Text Available AIMS: To clarify predictive values of C-reactive protein (CRP and high-molecular-weight (HMW adiponectin for development of metabolic syndrome. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of Japanese workers who had participated in an annual health checkup in 2007 and 2011. A total of 750 subjects (558 men and 192 women, age 46±8 years who had not met the criteria of metabolic syndrome and whose CRP and HMW-adiponectin levels had been measured in 2007 were enrolled in this study. Associations between CRP, HMW-adiponectin and development of metabolic syndrome after 4 years were assessed by logistic regression analysis and their predictive values were compared by receiver operating characteristic analysis. RESULTS: Among 750 subjects, 61 (8.1% developed metabolic syndrome defined by modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III criteria and 53 (7.1% developed metabolic syndrome defined by Japan Society for the Study of Obesity (JASSO in 2011. Although CRP and HMW-adiponectin were both significantly correlated with development of metabolic syndrome, multivariate logistic regression analysis revealed that HMW-adiponectin but not CRP was associated with metabolic syndrome independently of BMI or waist circumference. Adding these biomarkers to BMI or waist circumference did not improve the predictive value for metabolic syndrome. CONCLUSION: Our findings indicate that the traditional markers of adiposity such as BMI or waist circumference remain superior markers for predicting metabolic syndrome compared to CRP, HMW-adiponectin, or the combination of both among the Japanese population.

  20. Peripheral nerve P2 basic protein and the Guillain-Barre syndrome : In vitro demonstration of P2-specific antibody-secreting cells

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Jong, W.A.C. de; Demel, R.A.; Heijnen, C.J.; Ballieux, R.E.

    1984-01-01

    An immune response to the peripheral nerve basic protein P2 may be operative in the pathogenesis of the Guillain-Barré syndrome (GBS). A method is described for the purification of P2 of human origin. Purified P2 was used to investigate whether lymphocytes derived from peripheral blood of GBS

  1. Urinary albumin excretion and its relation with C-reactive protein and the metabolic syndrome in the prediction Of type 2 diabetes

    NARCIS (Netherlands)

    Brantsma, AH; Bakker, SJL; Hillege, HL; De Zeeuw, D; De Jong, PE; Gansevoort, RT

    2005-01-01

    OBJECTIVE - To investigate urinary albumin excretion (UAE) and its relation with C-reactive protein (CRP) and the metabolic syndrome in the prediction of the development of type 2 diabetes. RESEARCH DESIGN AND METHODS - We used data from the Prevention of Renal and Vascular End Stage Disease (PREVEN

  2. Peripheral nerve P2 basic protein and the Guillain-Barre syndrome : In vitro demonstration of P2-specific antibody-secreting cells

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Jong, W.A.C. de; Demel, R.A.; Heijnen, C.J.; Ballieux, R.E.

    1984-01-01

    An immune response to the peripheral nerve basic protein P2 may be operative in the pathogenesis of the Guillain-Barré syndrome (GBS). A method is described for the purification of P2 of human origin. Purified P2 was used to investigate whether lymphocytes derived from peripheral blood of GBS patien

  3. Pregnancy associated plasma protein A, a potential marker for vulnerable plaque in patients with non-ST-segment elevation acute coronary syndrome

    DEFF Research Database (Denmark)

    Iversen, Kasper; Teisner, Ane S; Teisner, Borge

    2009-01-01

    OBJECTIVES: To describe the presence and time-related pattern of circulating pregnancy associated plasma protein A (PAPP-A) levels in patients with non ST-segment elevation acute coronary syndrome (NSTE-ACS). DESIGN AND METHODS: Consecutively admitted patients (N=573) with clinical signs of NSTE-...

  4. Peripheral nerve P2 basic protein and the Guillain-Barre syndrome : In vitro demonstration of P2-specific antibody-secreting cells

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Jong, W.A.C. de; Demel, R.A.; Heijnen, C.J.; Ballieux, R.E.

    1984-01-01

    An immune response to the peripheral nerve basic protein P2 may be operative in the pathogenesis of the Guillain-Barré syndrome (GBS). A method is described for the purification of P2 of human origin. Purified P2 was used to investigate whether lymphocytes derived from peripheral blood of GBS patien

  5. Low-carbohydrate/high-protein diet improves diastolic cardiac function and the metabolic syndrome in overweight-obese patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    H. von Bibra

    2014-03-01

    Conclusions: These data indicate, that a low-glycaemic/high-protein but not a low-fat/high-carbohydrate nutrition modulates diastolic dysfunction in overweight T2D patients, improves insulin resistance and may prevent or delay the onset of diabetic cardiomyopathy and the metabolic syndrome.

  6. Effect of a High-Protein Diet versus Standard-Protein Diet on Weight Loss and Biomarkers of Metabolic Syndrome: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Ismael Campos-Nonato

    2017-06-01

    Full Text Available Background: Some studies have shown that protein-enriched diets can lead to greater weight loss and improvements in biomarkers of metabolic syndrome (MeS than standard protein diets. Therefore, the aim of this study was to determine the effect of increased protein intake on weight loss in Mexican adults with MeS. Methods: Randomized controlled trial in 118 adults aged 47.4 ± 11.5 years and meeting the established criteria for MeS were randomized to prescribed hypocaloric diets (500 kcal less than resting metabolic rate providing either 0.8 g/kg body weight (standard protein diet (SPD or 1.34 g/kg body weight (higher protein diet (HPD for 6 months. Body weight, waist circumference, percent body fat by bioimpedance analysis, fasting blood glucose, fasting insulin, hemoglobin A1c, total cholesterol, high-density lipoprotein (HDL cholesterol, very-low-density lipoprotein (VLDL cholesterol, triglycerides, C-reactive protein, creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase were measured at baseline, 3 months and at 6 months. Results: There were 105 subjects (51 for SPD and 54 for HPD who completed the trial. Overall weight loss was 5.1 ± 3.6 kg in the SPD group compared to 7.0 ± 3.7 kg in the in HPD group. Both groups lost a significant percent of centimeters of waist circumference (SPD -6.5 ± 2.6 cm and HPD -8.8 ± 2.6 cm. There was no statistical difference Except for the varying weight losses the two groups did not show any further differences overall. However in the subgroup judged to be adherent more than 75% of the time with the prescribed diets, there was a significant difference in mean weight loss (SPD -5.8% vs. HPD -9.5% after adjusting for baseline BMI. Both groups demonstrated significant decreases in waist circumference, glucose, insulin, triglycerides, and VLDL cholesterol, but there were no differences between the groups. There were no changes in blood tests for

  7. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage.

    Science.gov (United States)

    Stewart, Grant S; Panier, Stephanie; Townsend, Kelly; Al-Hakim, Abdallah K; Kolas, Nadine K; Miller, Edward S; Nakada, Shinichiro; Ylanko, Jarkko; Olivarius, Signe; Mendez, Megan; Oldreive, Ceri; Wildenhain, Jan; Tagliaferro, Andrea; Pelletier, Laurence; Taubenheim, Nadine; Durandy, Anne; Byrd, Philip J; Stankovic, Tatjana; Taylor, A Malcolm R; Durocher, Daniel

    2009-02-06

    The biological response to DNA double-strand breaks acts to preserve genome integrity. Individuals bearing inactivating mutations in components of this response exhibit clinical symptoms that include cellular radiosensitivity, immunodeficiency, and cancer predisposition. The archetype for such disorders is Ataxia-Telangiectasia caused by biallelic mutation in ATM, a central component of the DNA damage response. Here, we report that the ubiquitin ligase RNF168 is mutated in the RIDDLE syndrome, a recently discovered immunodeficiency and radiosensitivity disorder. We show that RNF168 is recruited to sites of DNA damage by binding to ubiquitylated histone H2A. RNF168 acts with UBC13 to amplify the RNF8-dependent histone ubiquitylation by targeting H2A-type histones and by promoting the formation of lysine 63-linked ubiquitin conjugates. These RNF168-dependent chromatin modifications orchestrate the accumulation of 53BP1 and BRCA1 to DNA lesions, and their loss is the likely cause of the cellular and developmental phenotypes associated with RIDDLE syndrome.

  8. Eutrophic urban ponds suffer from cyanobacterial blooms: Dutch examples

    NARCIS (Netherlands)

    Waajen, Guido W. A. M.; Faassen, Elisabeth J.; Lurling, Miquel

    2014-01-01

    Ponds play an important role in urban areas. However, cyanobacterial blooms counteract the societal need for a good water quality and pose serious health risks for citizens and pets. To provide insight into the extent and possible causes of cyanobacterial problems in urban ponds, we conducted a surv

  9. Controlling eutrophication by combined bloom precipitation and sediment phosphorus inactivation

    NARCIS (Netherlands)

    Lürling, M.F.L.L.W.; Oosterhout, J.F.X.

    2013-01-01

    The hypothesis that the combination of the flocculent polyaluminium chloride (PAC) with the lanthanum-modified bentonite Phoslock® (Flock & Lock) could sink effectively a water bloom of cyanobacteria and could shift a turbid, cyanobacteria infested lake to a clear water lake was tested in a

  10. Developing Learning Objectives for Accounting Ethics Using Bloom's Taxonomy

    Science.gov (United States)

    Kidwell, Linda A.; Fisher, Dann G.; Braun, Robert L.; Swanson, Diane L.

    2013-01-01

    The purpose of our article is to offer a set of core knowledge learning objectives for accounting ethics education. Using Bloom's taxonomy of educational objectives, we develop learning objectives in six content areas: codes of ethical conduct, corporate governance, the accounting profession, moral development, classical ethics theories, and…

  11. Mitigating cyanobacterial blooms: how effective are 'effective microorganisms'?

    NARCIS (Netherlands)

    Lürling, M.F.L.L.W.; Tolman, Y.; Euwe, M.

    2009-01-01

    This study examined the effects of 'Effective Microorganisms (EM)' on the growth of cyanobacteria, and their ability to terminate cyanobacterial blooms. The EM was tested in the form of 'mudballs' or 'Bokashi-balls', and as a suspension (EM-A) in laboratory experiments. No growth inhibition was obse

  12. Controlling eutrophication by combined bloom precipitation and sediment phosphorus inactivation

    NARCIS (Netherlands)

    Lürling, M.F.L.L.W.; Oosterhout, J.F.X.

    2013-01-01

    The hypothesis that the combination of the flocculent polyaluminium chloride (PAC) with the lanthanum-modified bentonite Phoslock® (Flock & Lock) could sink effectively a water bloom of cyanobacteria and could shift a turbid, cyanobacteria infested lake to a clear water lake was tested in a cont

  13. Allelopathic control of cyanobacterial blooms by periphyton biofilms.

    Science.gov (United States)

    Wu, Yonghong; Liu, Jiantong; Yang, Linzhang; Chen, Hong; Zhang, Shanqing; Zhao, Huijun; Zhang, Naiming

    2011-03-01

    Periphyton biofilms are natural mixtures comprised of photoautotrophic and heterotrophic complex microorganisms. In this work, the inhibition effects of periphyton biofilms on cyanobacterial blooms were studied in pilot and field trials. Results show that the cyanobacterial species responsible for the blooms had an upper nutrient concentration threshold, below which it could not effectively compete with other organisms in the periphyton. The disappearance of the cyanobacterial blooms was due to the allelopathy between the cyanobacteria and periphyton biofilm. In particular, it was found that the periphyton biofilm could produce water-soluble allelochemicals such as indole and 3-oxo-α-ionone to significantly inhibit the growth of the cyanobacteria. These allelochemicals are able to damage the thylakoid membranes of the cyanobacteria, interrupt the electron transport in photosystem II, decrease effective quantum yields, and eventually lead to the failure of photosynthesis. A comprehensive discussion on the ecological consequences of these findings is also presented. This work demonstrates the potential of periphyton biofilm to be used as an environmentally friendly ecological engineering solution for (i) the control of cyanobacterial blooms and (ii) a transitional means for the construction of beneficial conditions for ecosystem restoration. In addition, this work provides significant insights into the competitive relationships between algae and biofilms.

  14. Then the Wilderness Shall Bloom like a Rosy Bower

    DEFF Research Database (Denmark)

    Nielsen, Kirsten

    2014-01-01

    intertextual connections to the rest of the book. In my article, I have analysed how the Danish poet N.F.S. Grundtvig reworks Isa 35 in his hymn “Then the wilderness shall bloom like a rosy bower”, and how he reinterprets the wild animals as the Enemy (the Devil). In my view, the animals in Isa 35 have...

  15. Fungal parasitism: life cycle, dynamics and impact on cyanobacterial blooms.

    Directory of Open Access Journals (Sweden)

    Mélanie Gerphagnon

    Full Text Available Many species of phytoplankton are susceptible to parasitism by fungi from the phylum Chytridiomycota (i.e. chytrids. However, few studies have reported the effects of fungal parasites on filamentous cyanobacterial blooms. To investigate the missing components of bloom ecosystems, we examined an entire field bloom of the cyanobacterium Anabaena macrospora for evidence of chytrid infection in a productive freshwater lake, using a high resolution sampling strategy. A. macrospora was infected by two species of the genus Rhizosiphon which have similar life cycles but differed in their infective regimes depending on the cellular niches offered by their host. R. crassum infected both vegetative cells and akinetes while R. akinetum infected only akinetes. A tentative reconstruction of the developmental stages suggested that the life cycle of R. crassum was completed in about 3 days. The infection affected 6% of total cells (and 4% of akinètes, spread over a maximum of 17% of the filaments of cyanobacteria, in which 60% of the cells could be parasitized. Furthermore, chytrids may reduce the length of filaments of Anabaena macrospora significantly by "mechanistic fragmentation" following infection. All these results suggest that chytrid parasitism is one of the driving factors involved in the decline of a cyanobacteria blooms, by direct mortality of parasitized cells and indirectly by the mechanistic fragmentation, which could weaken the resistance of A. macrospora to grazing.

  16. Dynamic Soft Reduction for Continuously Cast Rail Bloom

    Institute of Scientific and Technical Information of China (English)

    CHEN Yong; LI Gui-jun; YANG Su-bo; ZHU Miao-yong

    2007-01-01

    Center porosity and centerline segregation in continuously cast bloom can be minimized by the well-known method of dynamic soft reduction. Metallurgical results of soft reduction previously employed in continuous bloom casting for heavy rail steel in Panzhihua Iron and Steel Group were not fully achieved because of the improper soft reduction process. Therefore, experiments for optimizing the process parameters of soft reduction for bloom were carried out. The results show that the proportion of the center porosity, which is less than 1.0, increases from 28.41% to 99.81%, while the proportion of the centerline segregation class increases from 40.91% to 100%, and the proportion of the central cavity increases from 92.05% to 100%, whereas the center carbon segregation index decreases from 1.17 to 1.05. The internal quality and the mechanical performance of the rails produced from continuously cast blooms meet the requirement of high-speed tracks of 350 km/h.

  17. ENCLOSURE EXPERIMENTS ON AND LACUSTRINE PRACTICE FOR ELIMINATING MICROCYSTIS BLOOM

    Institute of Scientific and Technical Information of China (English)

    刘建康; 谢平

    2002-01-01

    Microcystis bloom, one of the most objectionable characteristics of eutrophication in tropical and subtropical waters, occurred in Donghu Lake (East Lake) of Wuhan every summer from the 1970s up to 1984, but from 1985 up tonow failed to occur there. The cause of its disappearance remained in obscurityuntil recently. In situ enclosure experiments in the lake for three years showed that the stocking of the filter-feeding silver carp (Hypophthalmichthys molitrix) and big-head carp (Aristichthys nobilis) played a decisive role in eliminating Microcystis bloom from the lake; but that recurrence of the bloom is possibleunder certain conditions. This paper presents the details and the results of enclosure experiments. The authors' analysis of fish biomass data obtained by echo-sounding and the fishery production of the lake over the years, revealed that the recurrence of Microcystis bloom can be prevented so long as the combined biomass of silver carp and big-head carp remains at or exceeds 50 g per cubic meter of lakewater, as was the case in the lake's 1985 fish yield of 1015 t.``

  18. Hirsch, Bloom, and the Proper Ends of Education.

    Science.gov (United States)

    Ward, Jerry W., Jr.

    1989-01-01

    Urges teachers to use E. D. Hirsch's "Cultural Literacy" and Allan Bloom's "The Closing of the American Mind" as tools to explore what to teach and why to teach it. Concludes that in this way, teachers will be socially and morally responsible promoters of democratic literacy. (MM)

  19. Fungal parasitism: life cycle, dynamics and impact on cyanobacterial blooms.

    Science.gov (United States)

    Gerphagnon, Mélanie; Latour, Delphine; Colombet, Jonathan; Sime-Ngando, Télesphore

    2013-01-01

    Many species of phytoplankton are susceptible to parasitism by fungi from the phylum Chytridiomycota (i.e. chytrids). However, few studies have reported the effects of fungal parasites on filamentous cyanobacterial blooms. To investigate the missing components of bloom ecosystems, we examined an entire field bloom of the cyanobacterium Anabaena macrospora for evidence of chytrid infection in a productive freshwater lake, using a high resolution sampling strategy. A. macrospora was infected by two species of the genus Rhizosiphon which have similar life cycles but differed in their infective regimes depending on the cellular niches offered by their host. R. crassum infected both vegetative cells and akinetes while R. akinetum infected only akinetes. A tentative reconstruction of the developmental stages suggested that the life cycle of R. crassum was completed in about 3 days. The infection affected 6% of total cells (and 4% of akinètes), spread over a maximum of 17% of the filaments of cyanobacteria, in which 60% of the cells could be parasitized. Furthermore, chytrids may reduce the length of filaments of Anabaena macrospora significantly by "mechanistic fragmentation" following infection. All these results suggest that chytrid parasitism is one of the driving factors involved in the decline of a cyanobacteria blooms, by direct mortality of parasitized cells and indirectly by the mechanistic fragmentation, which could weaken the resistance of A. macrospora to grazing.

  20. Using Bloom To Bridge the WAC/WID Divide.

    Science.gov (United States)

    Cross, Geoffrey; Wills, Katherine

    A longitudinal study combined Stephen Tsuchdi's Workaday activities with Bloom's taxonomy of educational objectives to bridge the WAC/WID (writing across the curriculum/writing in the disciplines) divide. The researchers hoped that by combining concrete activities that can be applied across disciplines with a Bloomian conceptual framework of…