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Sample records for aldrich research biochemicals

  1. 78 FR 12102 - Manufacturer of Controlled Substances; Notice of Application; Sigma Aldrich Research Biochemicals...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Sigma Aldrich... Administration (DEA) to be registered as a bulk manufacturer of the following classes of controlled...

  2. 77 FR 60145 - Manufacturer of Controlled Substances; Notice of Application; Sigma Aldrich Research Biochemicals...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-02

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Sigma Aldrich..., Natick, Massachusetts 01760- 2447, made application by letter to the Drug Enforcement Administration...

  3. Biochemical Activities of the Wiskott-Aldrich Syndrome Homology Region 2 Domains of Sarcomere Length Short (SALS) Protein.

    PubMed

    Tóth, Mónika Ágnes; Majoros, Andrea Kinga; Vig, Andrea Teréz; Migh, Ede; Nyitrai, Miklós; Mihály, József; Bugyi, Beáta

    2016-01-08

    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.

  4. 78 FR 33442 - Manufacturer of Controlled Substances; Notice of Application Sigma Aldrich Research Biochemicals...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug..., Massachusetts 01760- 2447, made application by letter to the Drug Enforcement Administration (DEA) to be registered as a bulk manufacturer of the following basic classes of controlled substances: Drug Schedule...

  5. [Wiskott-Aldrich syndrome].

    PubMed

    Román Jiménez, María Guadalupe; Yamazaki Nakashimada, Marco Antonio; Blancas Galicia, Lizbeth

    2010-01-01

    The Wiskott-Aldrich syndrome is a primary immunodeficiency characterized by congenital microthrombocytopenia, eczema and recurrent infections. This paper reports the case of a 3-year-6-month male patient, whose maternal uncle died at the age of 3 months due to fulminant sepsis from a pulmonary infection. The patient was a product of the first pregnancy, he was born at 27 weeks' gestation and weighed 1,400 g. As a neonate he was hospitalized during the first 2 months of life because of a low gastrointestinal bleeding, thrombocytopenia and severe infections. In the next 4 months and before coming to our hospital the infant was hospitalized 54 times. On admission he presented disseminated dermatosis, enlarged neck lymph nodes and psychomotor retardation. Laboratory studies revealed hemoglobin 8.1 g/dL, platelets 31,000/uL, mean platelet volume 5.6 fL, IgM 39.3 mg/dL, IgA 67 mg/dL, IgG 1,380 mg/dL. On several occasions he received globular packages and platelet concentrates. The infusion of immunoglobulin G was started every 21 days. Bone marrow transplantation was delayed due to the complications that merited 13 hospitalizations and severe thrombocytopenia, low gastrointestinal bleeding, septic arthritis, infectious gastroenteritis, chronic suppurative otitis media and severe folliculitis. At the age of 4 years BMT of cord was performed, and 26 days after transplantation he presented septic shock and died. The prognosis of bone marrow transplantation in Wiskott-Aldrich syndrome and in other primary immunodeficiencies depends on the promptness of its performance at early stages in life. It is important that the first contact physicians be aware of the primary immunodeficiency signs and symptoms.

  6. Q & A with Ed Tech Leaders: Interview with Clark Aldrich

    ERIC Educational Resources Information Center

    Shaughnessy, Michael F.; Fulgham, Susan M.

    2016-01-01

    Clark Aldrich is the founder and Managing Partner of Clark Aldrich Designs, and is known as a global education visionary, industry analyst, and speaker. In this interview, he responds to questions about his ideas, his work, and his theories.

  7. Q & A with Ed Tech Leaders: Interview with Clark Aldrich

    ERIC Educational Resources Information Center

    Shaughnessy, Michael F.; Fulgham, Susan M.

    2016-01-01

    Clark Aldrich is the founder and Managing Partner of Clark Aldrich Designs, and is known as a global education visionary, industry analyst, and speaker. In this interview, he responds to questions about his ideas, his work, and his theories.

  8. [Wiskott-Aldrich Syndrome: An updated review].

    PubMed

    Blancas-Galicia, Lizbeth; Escamilla-Quiroz, Cecilia; Yamazaki-Nakashimada, Marco Antonio

    2011-01-01

    The Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency and is inherited in an X-linked pattern. Affected patients have mutations in the gene encoding Wiskott-Aldrich syndrome protein (WASP), a key regulator of signaling and reorganization of the cytoskeleton in hematopoietic cells. Mutations in WASP gene lead to a wide clinical spectrum ranging from thrombocytopenia, immunodeficiency, eczema and high susceptibility to tumor development and manifestations such as skin infections, suppurative otitis and pneumonia. Clinical symptoms start around the age of 6 months. Incidence of this disease is 1-10/millions of births. The laboratory tests show low platelet count and small size, but definitive diagnosis can only be confirmed by the demonstration of mutations in WASP gene. Treatment of WAS is based on antimicrobial therapy, prophylactic use of intravenous gamma globulin and bone marrow transplantation. Life expectancy in treated individuals is around 20 years but without treatment is 3.5 years.

  9. Wiskott-Aldrich Syndrome (WAS)

    MedlinePlus

    ... new treatments to improve health and expand scientific knowledge through research. WAS is a primary immune deficiency ... Helps Researchers Explore Microbial Genomic Data Biological Materials Biological ... Clinical Sciences Support Center Vaccine and Treatment Evaluation Units Topical ...

  10. The Design of Advanced Learning Engines: An Interview with Clark Aldrich

    ERIC Educational Resources Information Center

    Foreman, Joel; Aldrich, Clark

    2005-01-01

    This article presents an interview with Clark Aldrich, whose expertise as an "e-learning guru" (one of three identified by "Fortune" magazine in November 2000) rests on substantial foundations: his service as the Gartner Group research director who initiated and developed the firm's e-learning coverage, his leadership of the world class team that…

  11. The Design of Advanced Learning Engines: An Interview with Clark Aldrich

    ERIC Educational Resources Information Center

    Foreman, Joel; Aldrich, Clark

    2005-01-01

    This article presents an interview with Clark Aldrich, whose expertise as an "e-learning guru" (one of three identified by "Fortune" magazine in November 2000) rests on substantial foundations: his service as the Gartner Group research director who initiated and developed the firm's e-learning coverage, his leadership of the world class team that…

  12. Wiskott-Aldrich syndrome protein and platelets.

    PubMed

    Oda, A; Ochs, H D

    2000-12-01

    Wiskott-Aldrich syndrome (WAS) and X-linked thrombocy topenia (XLT) are caused by mutations of the WAS protein (WASP) gene. The manifestations of the classic WAS phenotype consist of immunodeficiency, eczema and thrombocytopenia. However, thrombocytopenia and small platelets are the only consistent features of WAS and XLT. The exact mechanisms of the development of thrombocytopenia in patients with WAS or XLT are unknown. To date, platelets are the only primary cells in which inducible tyrosine phosphorylation of WASP has been consistently demonstrated. This review focuses on the recent progress in dissecting the causes of thrombocytopenia and the emerging understanding of WASP phosphorylation.

  13. Rediscovering Thomas Bailey Aldrich's "The Story of a Bad Boy."

    ERIC Educational Resources Information Center

    West, Mark I.

    1998-01-01

    Discusses Thomas Bailey Aldrich's "The Story of a Bad Boy" (written in 1868), one of the first children's books in the United States to introduce realism to children's literature. Describes the book's appealing qualities, and Aldrich's life and career. Lists classic elements of the book, and suggests six activities for stimulating…

  14. [Wiskott-Aldrich syndrome. A report of a new mutation].

    PubMed

    Guillén-Rocha, Nelva; López-Rocha, Eunice; Danielian, Silvia; Segura-Méndez, Nora; López-González, Lucina; Lugo-Reyes, Saúl Oswaldo

    2014-01-01

    Wiskott-Aldrich syndrome was first reported clinically in 1937, and in 1954 the classic triad was identified: eccema, recurrent infections and thrombocytopenia with an X-linked transmission. Its incidence is estimated at 1 to 10 in one million live births per year. Wiskott Aldrich syndrome is caused by mutations in a gene in the short arm of chromosome X that encodes the Wiskott-Aldrich syndrome protein (WASp), which identification and sequencing was first performed in 1994, and since then about 300 mutations have been reported. This paper describes the case of a boy with Wiskott-Aldrich syndrome, with clinical and genetic diagnosis, with a considerable diagnostic delay attributable to an atypical presentation misdiagnosed as immune thrombocytopenia.

  15. Current and emerging treatment options for Wiskott-Aldrich syndrome.

    PubMed

    Worth, Austen J J; Thrasher, Adrian J

    2015-01-01

    Wiskott-Aldrich syndrome is a life-threatening primary immunodeficiency associated with a bleeding tendency, eczema and a high incidence of autoimmunity and malignancy. Stem cell transplantation offers the opportunity of cure for all these complications, and over the past 35 years there has been a remarkable improvement in survival following this treatment. Here, we review advances in management of clinical complications pre- and post-transplant, as well as discuss the morbidity Wiskott-Aldrich syndrome patients experience following treatment. For patients with a poorly matched stem cell donor, recent gene therapy trials demonstrate encouraging results and the potential of low-toxicity therapy for all patients.

  16. [Wiscott-Aldrich syndrome. Description of a case].

    PubMed

    Brai, M; Balsamo, V; Mogavero, S; Romano, N; Lagrutta, A

    1975-01-01

    The Wiscott-Aldrich syndrome with the classical symptomatology (eczema, thrombocytopenia and susceptibility to infections) has been described in a 3-month-old child. The family history, together with the evidence of an immunological deficiency involving both thymus-dependent lymphocyte and immunoglobulin-antibody systems have given important clues to diagnosis. Impairment of immunoglobulin homoeostasis and its relevance to the assessment of heterozygotes is discussed.

  17. Wiskott-Aldrich syndrome protein: Emerging mechanisms in immunity.

    PubMed

    Rivers, Elizabeth; Thrasher, Adrian J

    2017-08-14

    The Wiskott-Aldrich syndrome protein (WASP) participates in innate and adaptive immunity through regulation of actin cytoskeleton-dependent cellular processes, including immune synapse formation, cell signaling, migration and cytokine release. There is also emerging evidence for a direct role in nuclear transcription programmes uncoupled from actin polymerization. A deeper understanding of some of the more complex features of Wiskott Aldrich syndrome (WAS) itself, such as the associated autoimmunity and inflammation, has come from identification of defects in the number and function of anti-inflammatory myeloid cells and regulatory T and B cells, as well as defects in positive and negative B-cell selection. In this review we outline the cellular defects that have been characterized in both human WAS patients and murine models of the disease. We will emphasize in particular recent discoveries that provide a mechanistic insight into disease pathology, including lymphoid and myeloid cell homeostasis, immune synapse assembly and immune cell signaling. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Present status of biochemical research on the insecticide resistance problem*

    PubMed Central

    Agosin, Moises

    1963-01-01

    In order to provide a rational basis for the development of new insecticides, a thorough understanding of resistance mechanisms is necessary and this presupposes a detailed knowledge of the normal biochemical pathways in insects. The author reviews recent progress in this field, particularly the work on enzymatic detoxication of insecticides which appears to be the most important single factor in the production of resistance. The mechanisms include dehydrochlorination and α-methylenic oxidation (DDT), hydrolysis by phosphatases or carboxyesterases (organophosphorus compounds), and oxidation by microsomal enzyme systems (various classes of insecticides). Much work still needs to be done on the enzyme systems involved, especially in relation to substrate specificity and the effect of enzyme inhibitors that might act as synergists of insecticides. PMID:20604178

  19. Biochem-Env: a platform of biochemistry for research in environmental and agricultural sciences.

    PubMed

    Cheviron, Nathalie; Grondin, Virginie; Mougin, Christian

    2017-04-07

    Biochemical indicators are potent tools to assess ecosystem functioning under anthropic and global pressures. Nevertheless, additional work is needed to improve the methods used for the measurement of these indicators, and for a more relevant interpretation of the obtained results. To face these challenges, the platform Biochem-Env aims at providing innovative and standardized measurement protocols, as well as database and information system favoring result interpretation and opening. Its skills and tools are also offered for expertise, consulting, training, and standardization. In addition, the platform is a service of a French Research Infrastructure for Analysis and Experimentation on Ecosystems, for research in environmental and agricultural sciences.

  20. Developmental expression of Drosophila Wiskott-Aldrich Syndrome family proteins

    PubMed Central

    Rodriguez-Mesa, Evelyn; Abreu-Blanco, Maria Teresa; Rosales-Nieves, Alicia E.; Parkhurst, Susan M.

    2012-01-01

    Background Wiskott-Aldrich Syndrome (WASP) family proteins participate in many cellular processes involving rearrangements of the actin cytoskeleton. To the date, four WASP subfamily members have been described in Drosophila: Wash, WASp, SCAR, and Whamy. Wash, WASp, and SCAR are essential during early Drosophila development where they function in orchestrating cytoplasmic events including membrane-cytoskeleton interactions. A mutant for Whamy has not yet been reported. Results We generated monoclonal antibodies that are specific to Drosophila Wash, WASp, SCAR, and Whamy, and use these to describe their spatial and temporal localization patterns. Consistent with the importance of WASP family proteins in flies, we find that Wash, WASp, SCAR, and Whamy are dynamically expressed throughout oogenesis and embryogenesis. For example, we find that Wash accumulates at the oocyte cortex. WASp is highly expressed in the PNS, while SCAR is the most abundantly expressed in the CNS. Whamy exhibits an asymmetric subcellular localization that overlaps with mitochondria and is highly expressed in muscle. Conclusion All four WASP family members show specific expression patterns, some of which reflect their previously known roles and others revealing new potential functions. The monoclonal antibodies developed offer valuable new tools to investigate how WASP family proteins regulate actin cytoskeleton dynamics. PMID:22275148

  1. Wiskott-Aldrich syndrome in a child presenting with macrothrombocytopenia.

    PubMed

    Bastida, Jose Maria; Del Rey, Monica; Revilla, Nuria; Benito, Rocio; Perez-Andrés, Martin; González, Berta; Riesco, Susana; Janusz, Kamila; Padilla, Jose; Hortal Benito-Sendin, Ana; Bueno, David; Blanco, Elena; Hernández-Rivas, Maria; Vicente, Vicente; Rivera, Jose; González-Porras, Ramon; Lozano, Maria Luisa

    2017-06-01

    Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease resulting from variants in the WAS gene, characterized by a triad of immunodeficiency, eczema, and thrombocytopenia. Despite the fact that WAS is traditionally differentiated from immune thrombocytopenia (ITP) by small size of WAS platelets, in practice, microthrombocytopenia may occasionally not be present, and in certain cases, WAS patients exhibit some parallelism to ITP patients. We characterized one patient presenting with the classic form of the disease but increased mean platelet volume. Molecular studies revealed a novel hemizygous 1-bp deletion in WAS gene, c.802delC, leading to a frameshift and stop codon at amino acid 308 (p.Arg268Glyfs*40). Next-generation sequencing of a total of 70 additional genes known to harbor variants implicated in inherited platelet disorders did not identify additional defects. The pathogenesis of macrothrombocytopenia in this case is not known, but probably the coexistence of a still unidentified additional genetic variant might be involved.

  2. In memoriam: John Warren Aldrich, 1906-1995

    USGS Publications Warehouse

    Banks, Richard C.

    1997-01-01

    John Aldrich was born in Providence, Rhode Island, on 23 February 1906, and went to the Providence public schools. He developed a broad interest in natural history at an early age, being stimulated by his mother, a kindergarten teacher, who introduced him to nature books. His interest was strengthened by Harold L. Madison, Director of the Park Museum in Providence, an Associate ( = member) of the AOU. As a high school student, John taught nature study at the Rhode Island Boy Scout Camp in summers. John was President of his class at Classical High School, and manager of the school's football team in his senior year. Also in that year, 1923, John published his first paper, a note in Bird-Lore on the occurrence of the Mockingbird in Rhode Island. That paper is a literary gem, showing that his skill in writing developed as early as his knowledge of birds. His early interest in football continued as well; he was a devoted fan of the Washington Redskins in his later years.

  3. Autoimmunity in Wiskott–Aldrich Syndrome: An Unsolved Enigma

    PubMed Central

    Catucci, Marco; Castiello, Maria Carmina; Pala, Francesca; Bosticardo, Marita; Villa, Anna

    2012-01-01

    Wiskott–Aldrich Syndrome (WAS) is a severe X-linked Primary Immunodeficiency that affects 1–10 out of 1 million male individuals. WAS is caused by mutations in the WAS Protein (WASP) expressing gene that leads to the absent or reduced expression of the protein. WASP is a cytoplasmic protein that regulates the formation of actin filaments in hematopoietic cells. WASP deficiency causes many immune cell defects both in humans and in the WAS murine model, the Was−/− mouse. Both cellular and humoral immune defects in WAS patients contribute to the onset of severe clinical manifestations, in particular microthrombocytopenia, eczema, recurrent infections, and a high susceptibility to develop autoimmunity and malignancies. Autoimmune diseases affect from 22 to 72% of WAS patients and the most common manifestation is autoimmune hemolytic anemia, followed by vasculitis, arthritis, neutropenia, inflammatory bowel disease, and IgA nephropathy. Many groups have widely explored immune cell functionality in WAS partially explaining how cellular defects may lead to pathology. However, the mechanisms underlying the occurrence of autoimmune manifestations have not been clearly described yet. In the present review, we report the most recent progresses in the study of immune cell function in WAS that have started to unveil the mechanisms contributing to autoimmune complications in WAS patients. PMID:22826711

  4. 77 FR 67675 - Importer of Controlled Substances, Notice of Registration, SA INTL GMBH C/O., Sigma Aldrich Co...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ... Enforcement Administration Importer of Controlled Substances, Notice of Registration, SA INTL GMBH C/O., Sigma..., 2012, 77 FR 50162, SA INTL GMBH C/O., Sigma Aldrich Co., LLC., 3500 Dekalb Street, St. Louis, Missouri... C/O., Sigma Aldrich Co. LLC., to import the basic classes of controlled substances is...

  5. 78 FR 39339 - Importer of Controlled Substances; Notice of Registration; SA INTL GMBH C/O., Sigma Aldrich Co., LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... Substances; Notice of Registration; SA INTL GMBH C/O., Sigma Aldrich Co., LLC By Notice dated March 20, 2013, and published in the Federal Register on March 28, 2013, 78 FR 19015, SA INTL GMBH C/O., Sigma Aldrich... the factors in 21 U.S.C. 823(a) and 952(a), and determined that the registration of SA INTL GMBH...

  6. Detection of six novel mutations in WASP gene in fifteen Iranian Wiskott-Aldrich patients.

    PubMed

    Safaei, Sepideh; Fazlollahi, Mohammad Reza; Houshmand, Masoud; Hamidieh, Amir Ali; Bemanian, Mohammad Hassan; Alavi, Samin; Mousavi, Farideh; Pourpak, Zahra; Moin, Mostafa

    2012-12-01

    Wiskott-Aldrich syndrome (WAS) is a life-threatening X-linked recessive immunodeficiency disease described as a clinical triad of thrombocytopenia, eczema, and recurrent infections, caused by mutations of the WAS protein (WASP) gene. The milder form of this disease is X-linked thrombocytopenia (XLT) that presents only as platelet abnormalities. Mutation analysis for 15 boys with Wiskott-Aldrich syndrome was performed. Five previously reported mutations and six novel mutations including G8X, R41X, D283E, P412fsX446, E464X, and AfsX358 were detected.

  7. One-step surgical approach of a thoracic aortic aneurysm in Wiskott-Aldrich syndrome.

    PubMed

    Bernabeu, Eduardo; Josa, Miguel; Nomdedeu, Benet; Ramírez, José; García-Valentín, Antonio; Mestres, Carlos A; Mulet, Jaime

    2007-04-01

    Wiskott-Aldrich syndrome is a primary immunodeficiency characterized by infections, thrombocytopenia, and eczema. We present a 33-year-old man with this syndrome who underwent a one-stage ascending aorta, aortic arch and descending aortic aneurysm repair under moderate hypothermia and continuous visceral and cerebral perfusion. Histologic examination showed the presence of an aortitis with granulomatous inflammatory response and multinucleated cells.

  8. Glycan Arrays: From Basic Biochemical Research to Bioanalytical and Biomedical Applications

    NASA Astrophysics Data System (ADS)

    Geissner, Andreas; Seeberger, Peter H.

    2016-06-01

    A major branch of glycobiology and glycan-focused biomedicine studies the interaction between carbohydrates and other biopolymers, most importantly, glycan-binding proteins. Today, this research into glycan-biopolymer interaction is unthinkable without glycan arrays, tools that enable high-throughput analysis of carbohydrate interaction partners. Glycan arrays offer many applications in basic biochemical research, for example, defining the specificity of glycosyltransferases and lectins such as immune receptors. Biomedical applications include the characterization and surveillance of influenza strains, identification of biomarkers for cancer and infection, and profiling of immune responses to vaccines. Here, we review major applications of glycan arrays both in basic and applied research. Given the dynamic nature of this rapidly developing field, we focus on recent findings.

  9. Microchip-based cellular biochemical systems for practical applications and fundamental research: from microfluidics to nanofluidics.

    PubMed

    Xu, Yan; Jang, Kihoon; Yamashita, Tadahiro; Tanaka, Yo; Mawatari, Kazuma; Kitamori, Takehiko

    2012-01-01

    By combining cell technology and microchip technology, innovative cellular biochemical tools can be created from the microscale to the nanoscale for both practical applications and fundamental research. On the microscale level, novel practical applications taking advantage of the unique capabilities of microfluidics have been accelerated in clinical diagnosis, food safety, environmental monitoring, and drug discovery. On the other hand, one important trend of this field is further downscaling of feature size to the 10(1)-10(3) nm scale, which we call extended-nano space. Extended-nano space technology is leading to the creation of innovative nanofluidic cellular and biochemical tools for analysis of single cells at the single-molecule level. As a pioneering group in this field, we focus not only on the development of practical applications of cellular microchip devices but also on fundamental research to initiate new possibilities in the field. In this paper, we review our recent progress on tissue reconstruction, routine cell-based assays on microchip systems, and preliminary fundamental method for single-cell analysis at the single-molecule level with integration of the burgeoning technologies of extended-nano space.

  10. The Wiskott-Aldrich Syndrome: The Actin Cytoskeleton and Immune Cell Function

    PubMed Central

    Blundell, Michael P.; Worth, Austen; Bouma, Gerben; Thrasher, Adrian J.

    2010-01-01

    Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive primary immunodeficiency characterised by immune dysregulation, microthrombocytopaenia, eczema and lymphoid malignancies. Mutations in the WAS gene can lead to distinct syndrome variations which largely, although not exclusively, depend upon the mutation. Premature termination and deletions abrogate Wiskott-Aldrich syndrome protein (WASp) expression and lead to severe disease (WAS). Missense mutations usually result in reduced protein expression and the phenotypically milder X-linked thrombocytopenia (XLT) or attenuated WAS [1-3]. More recently however novel activating mutations have been described that give rise to X-linked neutropenia (XLN), a third syndrome defined by neutropenia with variable myelodysplasia [4-6]. WASP is key in transducing signals from the cell surface to the actin cytoskeleton, and a lack of WASp results in cytoskeletal defects that compromise multiple aspects of normal cellular activity including proliferation, phagocytosis, immune synapse formation, adhesion and directed migration. PMID:21178275

  11. Systemic vasculitis and aneurysm formation in the Wiskott-Aldrich syndrome.

    PubMed Central

    McCluggage, W G; Armstrong, D J; Maxwell, R J; Ellis, P K; McCluskey, D R

    1999-01-01

    A 24 year old male who suffered from the Wiskott-Aldrich syndrome developed intra-abdominal bleeding on two occasions. Radiological investigations showed aneurysmal dilatation of branches of the hepatic and superior mesenteric arteries. The second abdominal bleed necessitated laparotomy and the bleeding was localised to the kidneys. Right nephrectomy was performed and histological examination showed a necrotising vasculitis, mainly involving medium and small sized renal blood vessels. Steroids, immunosuppressive treatment, and control of blood pressure resulted in resolution of the vasculitic process and prevented further haemorrhage. Vasculitis and aneurysm formation are rarely described complications of Wiskott-Aldrich syndrome and may account for the life threatening haemorrhage which occurs in this condition. Images PMID:10560364

  12. Mutations of the Wiskott-Aldrich Syndrome Protein affect protein expression and dictate the clinical phenotypes.

    PubMed

    Ochs, Hans D

    2009-01-01

    Mutations of the Wiskott-Aldrich Syndrome Protein (WASP) are responsible for classic Wiskott-Aldrich Syndrome (WAS), X-linked thrombocytopenia (XLT), and in rare instances congenital X-linked neutropenia (XLN). WASP is a regulator of actin polymerization in hematopoietic cells with well-defined functional domains that are involved in cell signaling and cell locomotion, immune synapse formation, and apoptosis. Mutations of WASP are located throughout the gene and either inhibit or disregulate normal WASP function. Analysis of a large patient population demonstrates a strong phenotype-genotype correlation. Classic WAS occurs when WASP is absent, XLT when mutated WASP is expressed and XLN when missense mutations occur in the Cdc42-binding site. However, because there are exceptions to this rule it is difficult to predict the long-term prognosis of a given affected boy solely based on the analysis of WASP expression.

  13. Development of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome.

    PubMed

    Boztug, Kaan; Dewey, Ricardo A; Klein, Christoph

    2006-10-01

    Wiskott-Aldrich syndrome (WAS) is a complex primary immunodeficiency disorder associated with microthrombocytopenia, autoinnmunity and susceptibility to malignant lymphoma. At the molecular level, this rare disorder is caused by mutations in the gene encoding the Wiskott-Aldrich syndrome protein (WASP). WASP is a cytosolic adaptor protein mediating the rearrangement of the actin cytoskeleton upon surface receptor signaling. Allogenic hematopoietic stem cell (HSC) transplantation represents a curative approach but remains problematic in light of severe risks and side effects. Recently, HSC gene therapy has emerged as an alternative treatment option. Cumulative preclinical data obtained from WASP-deficient murine models and human cells indicate a marked improvement of the impaired cellular and immunological phenotypes associated with WASP deficiency. The first clinical trial is currently being conducted to assess the feasibility, toxicity, and potential therapeutic benefit of transplanting autologous WASP-reconstituted hematopoietic stem cells.

  14. Biochemical and Hematologic Reference Intervals for Aged Xenopus laevis in a Research Colony.

    PubMed

    Chang, Angela G; Hu, Jing; Lake, Elizabeth; Bouley, Donna M; Johns, Jennifer L

    2015-09-01

    Xenopus laevis, the African clawed frog, is commonly used in developmental and toxicology research studies. Little information is available on aged X. laevis; however, with the complete mapping of the genome and the availability of transgenic animal models, the number of aged animals in research colonies is increasing. The goals of this study were to obtain biochemical and hematologic parameters to establish reference intervals for aged X. laevis and to compare results with those from young adult X. laevis. Blood samples were collected from laboratory reared, female frogs (n = 52) between the ages of 10 and 14 y. Reference intervals were generated for 30 biochemistry analytes and full hematologic analysis; these data were compared with prior results for young X. laevis from the same vendor. Parameters that were significantly higher in aged compared with young frogs included calcium, calcium:phosphorus ratio, total protein, albumin, HDL, amylase, potassium, CO2, and uric acid. Parameters found to be significantly lower in aged frogs included glucose, AST, ALT, cholesterol, BUN, BUN:creatinine ratio, phosphorus, triglycerides, LDL, lipase, sodium, chloride, sodium:potassium ratio, and anion gap. Hematology data did not differ between young and old frogs. These findings indicate that chemistry reference intervals for young X. laevis may be inappropriate for use with aged frogs.

  15. Biochemical and Hematologic Reference Intervals for Aged Xenopus laevis in a Research Colony

    PubMed Central

    Chang, Angela G; Hu, Jing; Lake, Elizabeth; Bouley, Donna M; Johns, Jennifer L

    2015-01-01

    Xenopus laevis, the African clawed frog, is commonly used in developmental and toxicology research studies. Little information is available on aged X. laevis; however, with the complete mapping of the genome and the availability of transgenic animal models, the number of aged animals in research colonies is increasing. The goals of this study were to obtain biochemical and hematologic parameters to establish reference intervals for aged X. laevis and to compare results with those from young adult X. laevis. Blood samples were collected from laboratory reared, female frogs (n = 52) between the ages of 10 and 14 y. Reference intervals were generated for 30 biochemistry analytes and full hematologic analysis; these data were compared with prior results for young X. laevis from the same vendor. Parameters that were significantly higher in aged compared with young frogs included calcium, calcium:phosphorus ratio, total protein, albumin, HDL, amylase, potassium, CO2, and uric acid. Parameters found to be significantly lower in aged frogs included glucose, AST, ALT, cholesterol, BUN, BUN:creatinine ratio, phosphorus, triglycerides, LDL, lipase, sodium, chloride, sodium:potassium ratio, and anion gap. Hematology data did not differ between young and old frogs. These findings indicate that chemistry reference intervals for young X. laevis may be inappropriate for use with aged frogs. PMID:26424243

  16. Thermodynamic analysis of lignocellulosic biofuel production via a biochemical process: guiding technology selection and research focus.

    PubMed

    Sohel, M Imroz; Jack, Michael W

    2011-02-01

    The aim of this paper is to present an exergy analysis of bioethanol production process from lignocellulosic feedstock via a biochemical process to asses the overall thermodynamic efficiency and identify the main loss processes. The thermodynamic efficiency of the biochemical process was found to be 35% and the major inefficiencies of this process were identified as: the combustion of lignin for process heat and power production and the simultaneous scarification and co-fermentation process accounting for 67% and 27% of the lost exergy, respectively. These results were also compared with a previous analysis of a thermochemical process for producing biofuel. Despite fundamental differences, the biochemical and thermochemical processes considered here had similar levels of thermodynamic efficiency. Process heat and power production was the major contributor to exergy loss in both of the processes. Unlike the thermochemical process, the overall efficiency of the biochemical process largely depends on how the lignin is utilized.

  17. Disorders of regulatory T cell function in patients with the Wiskott-Aldrich syndrome.

    PubMed Central

    Zabay, J M; Fontán, G; Campos, A; García-Rodriguez, M C; Pascual-Salcedo, D; Bootello, A; de la Concha, E G

    1984-01-01

    Three patients with the Wiskott-Aldrich syndrome were studied. One of them had no past history of relevant infections. The other two presented different degrees of humoral and cellular immunodeficiency and their T cells in vitro showed a defect in regulatory activity of Ig production in PWM stimulated cultures. This defect was not observed in the third patient. All three had normal numbers of B cells, producing normal amounts of Ig in vitro when co-cultured with normal T cells. It is suggested that the immunoregulatory T cell abnormality might play an important role in the pathogenesis of the humoral immunodeficiency. PMID:6609033

  18. Research on: A. Reclamation of borrow pits and denuded lands; B. Biochemical aspects of mycorrhizae of forest trees

    SciTech Connect

    Marx, D.H.

    1990-12-01

    This report furnishes a list of compiled and ongoing studies and a list of publications which resulted from the research accomplished by Institute scientists and other collaborators. The research accomplished can be placed in four categories: I. Research on borrow pit rehabilitation with 12 publications; II. Research on artificial regeneration of southern pines with 34 publications; III. Research on artificial regeneration of eastern hardwoods with 16 publications; and IV. Cooperative research with the University of Georgia on biochemical aspects of mycorrhizae with 5 publications. Major accomplishments of this research are: 1. Procedures to successfully reclaim borrow pits with sludge, subsoiling and seedlings with specific mycorrhizae. 2. Protocols to successfully artificially regenerate southern pines (particularly ling leaf pine) and certain eastern hardwoods. 3. Basic understanding of the biochemistry of mycorrhizae and the discovery of a new pathway for sucrose utilization in plants. 67 refs.

  19. Molecular characterization of sialophorin (CD43), the lymphocyte surface sialoglycoprotein defective in Wiskott-Aldrich syndrome.

    PubMed Central

    Shelley, C S; Remold-O'Donnell, E; Davis, A E; Bruns, G A; Rosen, F S; Carroll, M C; Whitehead, A S

    1989-01-01

    Sialophorin (CD43) of leukocytes and platelets is a surface sialoglycoprotein that is phenotypically defective on lymphocytes of patients with the X chromosome-linked immunodeficiency Wiskott-Aldrich syndrome. Previous studies with monoclonal antibodies indicate that sialophorin is a component of a T-lymphocyte activation pathway. Here we describe the cDNA cloning and derived amino acid sequence of human sialophorin. The sequence predicts an integral membrane polypeptide with an N-terminal hydrophobic signal region followed by a mucin-like 235-residue extracellular region with a uniform distribution of 46 serine, 47 threonine, and 24 proline residues. This is followed by a 23-residue transmembrane region and a 123-residue C-terminal intracellular region. These latter regions have been highly conserved during evolution; the intracellular region contains a number of potential phosphorylation sites that might mediate transduction of activation signals. The chromosomal location of the sialophorin gene was determined and the implications of this assignment for the pathogenesis of the Wiskott-Aldrich syndrome are discussed. Images PMID:2784859

  20. The scurfy mouse mutant has previously unrecognized hematological abnormalities and resembles Wiskott-Aldrich syndrome.

    PubMed Central

    Lyon, M F; Peters, J; Glenister, P H; Ball, S; Wright, E

    1990-01-01

    The X chromosome-linked scurfy (sf) mutant of the mouse is recognized by the scaliness of the skin from which the name is derived and results in death of affected males at about 3-4 weeks of age. Consideration of known man-mouse homologies of the X chromosome prompted hematological studies, which have shown that the blood is highly abnormal. The platelet and erythrocyte counts are both reduced and become progressively lower relative to normal as the disease progresses. There is gastrointestinal bleeding, and most animals appear to die of severe anemia. By contrast, the leukocyte count is consistently raised. Some animals showed signs of infection but it is not yet clear whether there is immunodeficiency. Other features include the scaly skin and apparently reduced lateral growth of the skin, conjunctivitis, and diarrhea in some animals. The mutant resembles Wiskott-Aldrich syndrome in man, which is characterized by thrombocytopenia, eczema, diarrhea, and immunodeficiency. The loci of the human and mouse genes lie in homologous segments of the X chromosome, although apparently in somewhat different positions relative to other gene loci. Scurfy differs from Wiskott-Aldrich syndrome in that scurfy males are consistently hypogonadal. Images PMID:2320565

  1. Identification of Catalysts and Materials for a High-Energy Density Biochemical Fuel Cell: Cooperative Research and Development Final Report, CRADA Number CRD-09-345

    SciTech Connect

    Ghirardi, M.; Svedruzic, D.

    2013-07-01

    The proposed research attempted to identify novel biochemical catalysts, catalyst support materials, high-efficiency electron transfer agents between catalyst active sites and electrodes, and solid-phase electrolytes in order to maximize the current density of biochemical fuel cells that utilize various alcohols as substrates.

  2. A fence barrier method of leading edge cell capture for explorative biochemical research.

    PubMed

    Wager, Lucas J; Murray, Rachael Z; Thompson, Erik W; Leavesley, David I

    2017-02-17

    The scratch or wound-healing assay is used ubiquitously for investigating re-epithelialisation and has already revealed the importance of cells comprising the leading edge of healing epithelial wounds. However it is currently limited to studying the effect of known biochemical agents on the tissue of choice. Here we present an adaptation that extends the utility of this model to encompass the collection of cells from the leading edge of migrating epithelial sheets making available explorative biochemical analyses. The method is scalable and does not require expensive apparatus, making it suitable for large and small laboratories alike. We detail the application of our method and exemplify proof of principle data derived from primary human keratinocyte cultures.

  3. Unification of some biochemical methods of research in the pre- and post-flight periods

    NASA Technical Reports Server (NTRS)

    Tigranyan, R. A.

    1980-01-01

    The biochemical methods for determination of various parameters and factors during pre- and post-flight periods, as used by American and Soviet teams dealing with space flight medicine are compared. The emphasis is on the exchange of information on the study of the blood and urine content of space travelers before and after space flight. A series of electrolytic, enzymatic, and hormonal factors is discussed.

  4. 78 FR 19015 - Importer of Controlled Substances; Notice of Application; SA INTL GMBH C/O., Sigma Aldrich Co. LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-28

    ... Enforcement Administration Importer of Controlled Substances; Notice of Application; SA INTL GMBH C/O., Sigma... February 1, 2013, SA INTL GMBH C/O., Sigma Aldrich Co. LLC., 3500 Dekalb Street, St. Louis, Missouri 63118... (21 U.S.C. 952(a)(2)(B)) may, in the circumstances set forth in 21 U.S.C. 958(i), file comments...

  5. 77 FR 47106 - Manufacturer of Controlled Substances; Notice of Application; SA INTL GMBH C/O., Sigma Aldrich Co...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; SA INTL GMBH C/O... on May 2, 2012, SA INTL GMBH C/O., Sigma Aldrich Co. LLC., 3500 Dekalb Street, St. Louis,...

  6. 77 FR 50162 - Importer of Controlled Substances; Notice of Application; SA INTL GMBH C/O., Sigma Aldrich Co., LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances; Notice of Application; SA INTL GMBH C/O., Sigma Aldrich Co., LLC Correction In notice document 2012-19191 appearing on pages 47106-47108 in the issue...

  7. A Hydrophobic Pocket in the Active Site of Glycolytic Aldolase Mediates Interactions with Wiskott-Aldrich Syndrome Protein

    SciTech Connect

    St-Jean,M.; Izard, T.; Sygusch, J.

    2007-01-01

    Aldolase plays essential catalytic roles in glycolysis and gluconeogenesis. However, aldolase is a highly abundant protein that is remarkably promiscuous in its interactions with other cellular proteins. In particular, aldolase binds to highly acidic amino acid sequences, including the C-terminus of the Wiskott-Aldrich syndrome protein, an actin nucleation promoting factor. Here we report the crystal structure of tetrameric rabbit muscle aldolase in complex with a C-terminal peptide of Wiskott-Aldrich syndrome protein. Aldolase recognizes a short, 4-residue DEWD motif (residues 498-501), which adopts a loose hairpin turn that folds about the central aromatic residue, enabling its tryptophan side chain to fit into a hydrophobic pocket in the active site of aldolase. The flanking acidic residues in this binding motif provide further interactions with conserved aldolase active site residues, Arg-42 and Arg-303, aligning their side chains and forming the sides of the hydrophobic pocket. The binding of Wiskott-Aldrich syndrome protein to aldolase precludes intramolecular interactions of its C-terminus with its active site, and is competitive with substrate as well as with binding by actin and cortactin. Finally, based on this structure a novel naphthol phosphate-based inhibitor of aldolase was identified and its structure in complex with aldolase demonstrated mimicry of the Wiskott-Aldrich syndrome protein-aldolase interaction. The data support a model whereby aldolase exists in distinct forms that regulate glycolysis or actin dynamics.

  8. A risk factor analysis of outcomes after unrelated cord blood transplantation for children with Wiskott-Aldrich syndrome.

    PubMed

    Shekhovtsova, Zhanna; Bonfim, Carmem; Ruggeri, Annalisa; Nichele, Samantha; Page, Kristin; AlSeraihy, Amal; Barriga, Francisco; de Toledo Codina, José Sánchez; Veys, Paul; Boelens, Jaap Jan; Mellgren, Karin; Bittencourt, Henrique; O'Brien, Tracey; Shaw, Peter J; Chybicka, Alicja; Volt, Fernanda; Giannotti, Federica; Gluckman, Eliane; Kurtzberg, Joanne; Gennery, Andrew R; Rocha, Vanderson

    2017-06-01

    Wiskott-Aldrich syndrome is a severe X-linked recessive immune deficiency disorder. A scoring system of Wiskott-Aldrich syndrome severity (0.5-5) distinguishes two phenotypes: X-linked thrombocytopenia and classic Wiskott-Aldrich syndrome. Hematopoietic cell transplantation is curative for Wiskott-Aldrich syndrome; however, the use of unrelated umbilical cord blood transplantation has seldom been described. We analyzed umbilical cord blood transplantation outcomes for 90 patients. The median age at umbilical cord blood transplantation was 1.5 years. Patients were classified according to clinical scores [2 (23%), 3 (30%), 4 (23%) and 5 (19%)]. Most patients underwent HLA-mismatched umbilical cord blood transplantation and myeloablative conditioning with anti-thymocyte globulin. The cumulative incidence of neutrophil recovery at day 60 was 89% and that of grade II-IV acute graft-versus-host disease at day 100 was 38%. The use of methotrexate for graft-versus-host disease prophylaxis delayed engraftment (P=0.02), but decreased acute graft-versus-host disease (P=0.03). At 5 years, overall survival and event-free survival rates were 75% and 70%, respectively. The estimated 5-year event-free survival rates were 83%, 73% and 55% for patients with a clinical score of 2, 4-5 and 3, respectively. In multivariate analysis, age <2 years at the time of the umbilical cord blood transplant and a clinical phenotype of X-linked thrombocytopenia were associated with improved event-free survival. Overall survival tended to be better in patients transplanted after 2007 (P=0.09). In conclusion, umbilical cord blood transplantation is a good alternative option for young children with Wiskott-Aldrich syndrome lacking an HLA identical stem cell donor. Copyright© Ferrata Storti Foundation.

  9. A risk factor analysis of outcomes after unrelated cord blood transplantation for children with Wiskott-Aldrich syndrome

    PubMed Central

    Shekhovtsova, Zhanna; Bonfim, Carmem; Ruggeri, Annalisa; Nichele, Samantha; Page, Kristin; AlSeraihy, Amal; Barriga, Francisco; de Toledo Codina, José Sánchez; Veys, Paul; Boelens, Jaap Jan; Mellgren, Karin; Bittencourt, Henrique; O’Brien, Tracey; Shaw, Peter J.; Chybicka, Alicja; Volt, Fernanda; Giannotti, Federica; Gluckman, Eliane; Kurtzberg, Joanne; Gennery, Andrew R.; Rocha, Vanderson

    2017-01-01

    Wiskott-Aldrich syndrome is a severe X-linked recessive immune deficiency disorder. A scoring system of Wiskott-Aldrich syndrome severity (0.5–5) distinguishes two phenotypes: X-linked thrombocytopenia and classic Wiskott-Aldrich syndrome. Hematopoietic cell transplantation is curative for Wiskott-Aldrich syndrome; however, the use of unrelated umbilical cord blood transplantation has seldom been described. We analyzed umbilical cord blood transplantation outcomes for 90 patients. The median age at umbilical cord blood transplantation was 1.5 years. Patients were classified according to clinical scores [2 (23%), 3 (30%), 4 (23%) and 5 (19%)]. Most patients underwent HLA-mismatched umbilical cord blood transplantation and myeloablative conditioning with anti-thymocyte globulin. The cumulative incidence of neutrophil recovery at day 60 was 89% and that of grade II–IV acute graft-versus-host disease at day 100 was 38%. The use of methotrexate for graft-versus-host disease prophylaxis delayed engraftment (P=0.02), but decreased acute graft-versus-host disease (P=0.03). At 5 years, overall survival and event-free survival rates were 75% and 70%, respectively. The estimated 5-year event-free survival rates were 83%, 73% and 55% for patients with a clinical score of 2, 4–5 and 3, respectively. In multivariate analysis, age <2 years at the time of the umbilical cord blood transplant and a clinical phenotype of X-linked thrombocytopenia were associated with improved event-free survival. Overall survival tended to be better in patients transplanted after 2007 (P=0.09). In conclusion, umbilical cord blood transplantation is a good alternative option for young children with Wiskott-Aldrich syndrome lacking an HLA identical stem cell donor. PMID:28255019

  10. Wiskott-Aldrich syndrome proteins in the nucleus: aWASH with possibilities.

    PubMed

    Verboon, Jeffrey M; Sugumar, Bina; Parkhurst, Susan M

    2015-01-01

    Actin and proteins that regulate its dynamics or interactions have well-established roles in the cytoplasm where they function as key components of the cytoskeleton to control diverse processes, including cellular infrastructure, cellular motility, cell signaling, and vesicle transport. Recent work has also uncovered roles for actin and its regulatory proteins in the nucleus, primarily in mechanisms governing gene expression. The Wiskott Aldrich Syndrome (WAS) family of proteins, comprising the WASP/N-WASP, SCAR/WAVE, WHAMM/JMY/WHAMY, and WASH subfamilies, function in the cytoplasm where they activate the Arp2/3 complex to form branched actin filaments. WAS proteins are present in the nucleus and have been implicated as transcriptional regulators. We found that Drosophila Wash, in addition to transcriptional effects, is involved in global nuclear architecture. Here we summarize the regulation and function of nuclear WAS proteins, and highlight how our work with Wash expands the possibilities for the functions of these proteins in the nucleus.

  11. New insights into the biology of Wiskott-Aldrich syndrome (WAS).

    PubMed

    Thrasher, Adrian J

    2009-01-01

    The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disease with a characteristic clinical phenotype that includes thrombocytopenia with small platelets, eczema, recurrent infections due to immunodeficiency, and an increased incidence of autoimmune manifestations and malignancies. The identification of the molecular defect in the WAS gene has broadened the clinical spectrum of disease to include chronic or intermittent X-linked thrombocytopenia (XLT), a relatively mild form of WAS, and X-linked neutropenia (XLN) due to an arrest of myelopoiesis. The pathophysiological mechanisms relate to defective actin polymerization in hematopoietic cells as a result of deficient or dysregulated activity of the WAS protein (WASp). The severity of disease is variable and somewhat predictable from genotype. Treatment strategies therefore range from conservative through to early definitive intervention by using allogeneic hematopoietic stem cell transplantation and potentially somatic gene therapy. All aspects of the condition from clinical presentation to molecular pathology and basic cellular mechanisms have been reviewed recently.

  12. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome.

    PubMed

    Aiuti, Alessandro; Biasco, Luca; Scaramuzza, Samantha; Ferrua, Francesca; Cicalese, Maria Pia; Baricordi, Cristina; Dionisio, Francesca; Calabria, Andrea; Giannelli, Stefania; Castiello, Maria Carmina; Bosticardo, Marita; Evangelio, Costanza; Assanelli, Andrea; Casiraghi, Miriam; Di Nunzio, Sara; Callegaro, Luciano; Benati, Claudia; Rizzardi, Paolo; Pellin, Danilo; Di Serio, Clelia; Schmidt, Manfred; Von Kalle, Christof; Gardner, Jason; Mehta, Nalini; Neduva, Victor; Dow, David J; Galy, Anne; Miniero, Roberto; Finocchi, Andrea; Metin, Ayse; Banerjee, Pinaki P; Orange, Jordan S; Galimberti, Stefania; Valsecchi, Maria Grazia; Biffi, Alessandra; Montini, Eugenio; Villa, Anna; Ciceri, Fabio; Roncarolo, Maria Grazia; Naldini, Luigi

    2013-08-23

    Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency caused by mutations in the gene encoding WASP, a protein regulating the cytoskeleton. Hematopoietic stem/progenitor cell (HSPC) transplants can be curative, but, when matched donors are unavailable, infusion of autologous HSPCs modified ex vivo by gene therapy is an alternative approach. We used a lentiviral vector encoding functional WASP to genetically correct HSPCs from three WAS patients and reinfused the cells after a reduced-intensity conditioning regimen. All three patients showed stable engraftment of WASP-expressing cells and improvements in platelet counts, immune functions, and clinical scores. Vector integration analyses revealed highly polyclonal and multilineage haematopoiesis resulting from the gene-corrected HSPCs. Lentiviral gene therapy did not induce selection of integrations near oncogenes, and no aberrant clonal expansion was observed after 20 to 32 months. Although extended clinical observation is required to establish long-term safety, lentiviral gene therapy represents a promising treatment for WAS.

  13. Stem-Cell Gene Therapy for the Wiskott–Aldrich Syndrome

    PubMed Central

    Boztug, Kaan; Schmidt, Manfred; Schwarzer, Adrian; Banerjee, Pinaki P.; Díez, Inés Avedillo; Dewey, Ricardo A.; Böhm, Marie; Nowrouzi, Ali; Ball, Claudia R.; Glimm, Hanno; Naundorf, Sonja; Kühlcke, Klaus; Blasczyk, Rainer; Kondratenko, Irina; Maródi, László; Orange, Jordan S.; von Kalle, Christof; Klein, Christoph

    2010-01-01

    SUMMARY The Wiskott–Aldrich syndrome (WAS) is an X-linked recessive primary immunodeficiency disorder associated with thrombocytopenia, eczema, and autoimmunity. We treated two patients who had this disorder with a transfusion of autologous, genetically modified hematopoietic stem cells (HSC). We found sustained expression of WAS protein expression in HSC, lymphoid and myeloid cells, and platelets after gene therapy. T and B cells, natural killer (NK) cells, and monocytes were functionally corrected. After treatment, the patients’ clinical condition markedly improved, with resolution of hemorrhagic diathesis, eczema, autoimmunity, and predisposition to severe infection. Comprehensive insertion-site analysis showed vector integration that targeted multiple genes controlling growth and immunologic responses in a persistently polyclonal hematopoiesis. (Funded by Deutsche Forschungsgemeinschaft and others; German Clinical Trials Register number, DRKS00000330.) PMID:21067383

  14. Abnormalities of follicular helper T-cell number and function in Wiskott-Aldrich syndrome

    PubMed Central

    Zhang, Xuan; Dai, Rongxin; Li, Wenyan; Zhao, Hongyi; Zhang, Yongjie; Zhou, Lina; Du, Hongqiang; Luo, Guangjin; Wu, Junfeng; Niu, Linlin; An, Yunfei; Zhang, Zhiyong; Ding, Yuan; Song, Wenxia; Liu, Chaohong

    2016-01-01

    Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific regulator of actin nucleation. Wiskott-Aldrich syndrome (WAS) patients show immunodeficiencies, most of which have been attributed to defective T-cell functions. T follicular helper (Tfh) cells are the major CD4+ T-cell subset with specialized B-cell helper capabilities. Aberrant Tfh cells activities are involved in immunopathologies such as autoimmunity, immunodeficiencies, and lymphomas. We found that in WAS patients, the number of circulating Tfh cells was significantly reduced due to reduced proliferation and increased apoptosis, and Tfh cells were Th2 and Th17 polarized. The expression of inducible costimulator (ICOS) in circulating Tfh cells was higher in WAS patients than in controls. BCL6 expression was decreased in total CD4+ T and Tfh cells of WAS patients. Mirroring the results in patients, the frequency of Tfh cells in WAS knockout (KO) mice was decreased, as was the frequency of BCL6+ Tfh cells, but the frequency of ICOS+ Tfh cells was increased. Using WAS chimera mice, we found that the number of ICOS+ Tfh cells was decreased in WAS chimera mice, indicating that the increase in ICOS+ Tfh cells in WAS KO mice was cell extrinsic. The data from in vivo CD4+ naive T-cell adoptive transfer mice as well as in vitro coculture of naive B and Tfh cells showed that the defective function of WASp-deficient Tfh cells was T-cell intrinsic. Consistent findings in both WAS patients and WAS KO mice suggested an essential role for WASp in the development and memory response of Tfh cells and that WASp deficiency causes a deficient differentiation defect in Tfh cells by downregulating the transcription level of BCL6. PMID:27170596

  15. Outcome following Gene Therapy in Patients with Severe Wiskott-Aldrich Syndrome

    PubMed Central

    Abina, Salima Hacein-Bey; Gaspar, H. Bobby; Blondeau, Johanna; Caccavelli, Laure; Charrier, Sabine; Buckland, Karen; Picard, Capucine; Six, Emmanuelle; Himoudi, Nourredine; Gilmour, Kimberly; McNicol, Anne-Marie; Hara, Havinder; Xu-Bayford, Jinhua; Rivat, Christine; Touzot, Fabien; Mavilio, Fulvio; Lim, Annick; Treluyer, Jean-Marc; Héritier, Sébastien; Lefrere, Francois; Magalon, Jeremy; Pengue-Koyi, Isabelle; Honnet, Géraldine; Blanche, Stéphane; Sherman, Eric A.; Male, Frances; Berry, Charles; Malani, Nirav; Bushman, Frederic D.; Fischer, Alain; Thrasher, Adrian J.; Galy, Anne; Cavazzana, Marina

    2016-01-01

    Importance Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency associated with severe microthrombocytopenia. Partially HLA-matched allogeneic hematopoietic stem cell (HSC) transplantation is associated with significant co-morbidity. Objective To assess the outcome and safety of autologous HSC gene therapy in WAS. Design Gene-corrected autologous HSC were infused in 7 consecutive WAS patients (age range: 0.8 to 15.5 years, mean 7 years) following myeloablative conditioning. Setting and participants: Patients with severe WAS lacking HLA-matched related or unrelated HSC donors were treated between December 2010 and January 2014. The follow up of patients in this intermediate analysis ranged from 9 to 42 months. Intervention A single infusion of gene-modified CD34+ cells with an advanced lentiviral vector. Main Outcome(s) and Measure(s) Primary outcomes were improvement at 24 months in eczema, the frequency and severity of infections, bleeding tendency, autoimmunity and reduction in disease-related days of hospitalization. Secondary outcomes were improvement in immunological and haematological parameters, and evidence for safety through vector integration analysis. Results Six out of the 7 patients were alive at the time of last follow-up (mean and median follow-up time: 28 and 27 months respectively) and showed sustained clinical benefit. One patient died 7 months after treatment from pre-existing drug- resistant herpes virus infections. Eczema and susceptibility to infections resolved in all 6 patients. Autoimmunity improved in 5/5 patients. No severe bleeding episodes were recorded after treatment, and at last follow up 6/6 patients were free from blood product support and thrombopoietic agonists. Hospitalization days were reduced from 25 days (median) in the 2 years pretreatment to 0 days (median) in the 2 years post treatment. All 6 surviving patients exhibited high-level, stable engraftment of functionally corrected lymphoid cells. The degree of

  16. [Persistent thrombocytopenia in a child: morphological examination of blood platelets established the diagnosis of Wiskott-Aldrich syndrome].

    PubMed

    Latger-Cannard, V; Lacroix, F; Devignes, J; Salignac, S; Bensoussan, D; Salmon, A; Mansuy, L; Bordigoni, P; Lecompte, T

    2008-01-01

    Thrombocytopenia frequently occurs in laboratory practice. The present work illustrates, through the presentation of a case report of Wiskott-Aldrich syndrome, the difficulties encountered to identify and characterize thrombocytopenia. The clinicobiological validation of a low platelet count involves both the biologist, who must assume the validation of numeration while mentioning the morphological characteristics of the platelets and other blood cells, as well as the physician who has to interpret these data according to the clinical context.

  17. Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients.

    PubMed

    Pala, Francesca; Morbach, Henner; Castiello, Maria Carmina; Schickel, Jean-Nicolas; Scaramuzza, Samantha; Chamberlain, Nicolas; Cassani, Barbara; Glauzy, Salome; Romberg, Neil; Candotti, Fabio; Aiuti, Alessandro; Bosticardo, Marita; Villa, Anna; Meffre, Eric

    2015-10-01

    Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by microthrombocytopenia, eczema, and high susceptibility to developing tumors and autoimmunity. Recent evidence suggests that B cells may be key players in the pathogenesis of autoimmunity in WAS. Here, we assessed whether WAS protein deficiency (WASp deficiency) affects the establishment of B cell tolerance by testing the reactivity of recombinant antibodies isolated from single B cells from 4 WAS patients before and after gene therapy (GT). We found that pre-GT WASp-deficient B cells were hyperreactive to B cell receptor stimulation (BCR stimulation). This hyperreactivity correlated with decreased frequency of autoreactive new emigrant/transitional B cells exiting the BM, indicating that the BCR signaling threshold plays a major role in the regulation of central B cell tolerance. In contrast, mature naive B cells from WAS patients were enriched in self-reactive clones, revealing that peripheral B cell tolerance checkpoint dysfunction is associated with impaired suppressive function of WAS regulatory T cells. The introduction of functional WASp by GT corrected the alterations of both central and peripheral B cell tolerance checkpoints. We conclude that WASp plays an important role in the establishment and maintenance of B cell tolerance in humans and that restoration of WASp by GT is able to restore B cell tolerance in WAS patients.

  18. WIP null mice display a progressive immunological disorder that resembles Wiskott-Aldrich syndrome.

    PubMed

    Curcio, C; Pannellini, T; Lanzardo, S; Forni, G; Musiani, P; Antón, I M

    2007-01-01

    The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency syndrome caused by mutations in the WAS protein (WASP). This participates in signalling and cytoskeletal homoeostasis, and some of its activities are regulated by its binding to the WASP interacting protein (WIP). WIP deficiency, however, has not yet been shown to be of pathological significance in humans. Here we show that, in WIP null (WIP(-/-)) mice, it produces haematological alterations and anatomical abnormalities in several organs, most probably as a consequence of autoimmune attacks. Granulocytosis and severe lymphopenia are associated with a proportional increase in segmented cells and fewer bone marrow erythrocytes and lymphocytes. Splenomegaly is accompanied by an increase of haematopoietic tissue and red pulp, reduction of the white pulp, and fewer B (B220(+)) lymphocytes (also apparent in the lymph nodes and Peyer's patches). Ulcerative colitis, interstitial pneumonitis, glomerular nephropathy with IgA deposits, autoantibodies, and joint inflammation are also evident. These progressive immunological disorders closely mimic those seen in WAS. WIP deficiency may thus be implicated in some cases in which mutations in the gene encoding WASP are not detected. Copyright (c) 2006 Pathological Society of Great Britain and Ireland.

  19. The mitochondrial genome of Elodia flavipalpis Aldrich (Diptera: Tachinidae) and the evolutionary timescale of Tachinid flies.

    PubMed

    Zhao, Zhe; Su, Tian-Juan; Chesters, Douglas; Wang, Shi-di; Ho, Simon Y W; Zhu, Chao-Dong; Chen, Xiao-Lin; Zhang, Chun-Tian

    2013-01-01

    Tachinid flies are natural enemies of many lepidopteran and coleopteran pests of forests, crops, and fruit trees. In order to address the lack of genetic data in this economically important group, we sequenced the complete mitochondrial genome of the Palaearctic tachinid fly Elodia flavipalpis Aldrich, 1933. Usually found in Northern China and Japan, this species is one of the primary natural enemies of the leaf-roller moths (Tortricidae), which are major pests of various fruit trees. The 14,932-bp mitochondrial genome was typical of Diptera, with 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes. However, its control region is only 105 bp in length, which is the shortest found so far in flies. In order to estimate dipteran evolutionary relationships, we conducted a phylogenetic analysis of 58 mitochondrial genomes from 23 families. Maximum-likelihood and Bayesian methods supported the monophyly of both Tachinidae and superfamily Oestroidea. Within the subsection Calyptratae, Muscidae was inferred as the sister group to Oestroidea. Within Oestroidea, Calliphoridae and Sarcophagidae formed a sister clade to Oestridae and Tachinidae. Using a Bayesian relaxed clock calibrated with fossil data, we estimated that Tachinidae originated in the middle Eocene.

  20. Wiskott–Aldrich syndrome: review and report of a large family

    PubMed Central

    Stiehm, E. R.; McIntosh, R. M.

    1967-01-01

    Wiskott–Aldrich syndrome is a sex-linked recessive antibody-deficiency syndrome characterized by thrombocytopenia, eczema and increased susceptibility to infection. All forms of therapy are notably unsuccessful and these patients succumb in the first decade. Three cases of this syndrome are presented from a large family in which nine male infants have succumbed with manifestations of this disease. Two of the infants died at ages 10 months and 4 years respectively. A third child is alive at age 2. Serial quantitative immune globulin studies performed in two cases demonstrated markedly elevated γA, decreased γM and normal γG; levels of γM were initially normal but fell progressively as γA levels increased. The low levels of γM are probably a factor in their low or absent isoagglutinins, poor response to injected antigens, and increased susceptibility to infection; elevated γA levels may indicate immunologic unresponsiveness and/or a compensatory mechanism for the defect in γM synthesis. In two of these patients prolonged trials (17 and 23 months) of periodic plasma infusions (15 ml/kg at 6-week intervals), accompanied by γ-globulin injections (0·1 ml/kg) were undertaken. Although no remarkable effects on the platelets or their resistance to infection was noted, we feel that some benefit might have accrued and that further trails are indicated. PMID:4166240

  1. Wiskott-Aldrich syndrome proteins in the nucleus: aWASH with possibilities

    PubMed Central

    Verboon, Jeffrey M; Sugumar, Bina; Parkhurst, Susan M

    2015-01-01

    Actin and proteins that regulate its dynamics or interactions have well-established roles in the cytoplasm where they function as key components of the cytoskeleton to control diverse processes, including cellular infrastructure, cellular motility, cell signaling, and vesicle transport. Recent work has also uncovered roles for actin and its regulatory proteins in the nucleus, primarily in mechanisms governing gene expression. The Wiskott Aldrich Syndrome (WAS) family of proteins, comprising the WASP/N-WASP, SCAR/WAVE, WHAMM/JMY/WHAMY, and WASH subfamilies, function in the cytoplasm where they activate the Arp2/3 complex to form branched actin filaments. WAS proteins are present in the nucleus and have been implicated as transcriptional regulators. We found that Drosophila Wash, in addition to transcriptional effects, is involved in global nuclear architecture. Here we summarize the regulation and function of nuclear WAS proteins, and highlight how our work with Wash expands the possibilities for the functions of these proteins in the nucleus. PMID:26305109

  2. Gene therapy for Wiskott-Aldrich syndrome in a severely affected adult.

    PubMed

    Morris, Emma C; Fox, Thomas; Chakraverty, Ronjon; Tendeiro, Rita; Snell, Katie; Rivat, Christine; Grace, Sarah; Gilmour, Kimberly; Workman, Sarita; Buckland, Karen; Butler, Katie; Chee, Ronnie; Salama, Alan D; Ibrahim, Hazem; Hara, Havinder; Duret, Cecile; Mavilio, Fulvio; Male, Frances; Bushman, Frederick D; Galy, Anne; Burns, Siobhan O; Gaspar, H Bobby; Thrasher, Adrian J

    2017-09-14

    Until recently, hematopoietic stem cell transplantation was the only curative option for Wiskott-Aldrich syndrome (WAS). The first attempts at gene therapy for WAS using a ϒ-retroviral vector improved immunological parameters substantially but were complicated by acute leukemia as a result of insertional mutagenesis in a high proportion of patients. More recently, treatment of children with a state-of-the-art self-inactivating lentiviral vector (LV-w1.6 WASp) has resulted in significant clinical benefit without inducing selection of clones harboring integrations near oncogenes. Here, we describe a case of a presplenectomized 30-year-old patient with severe WAS manifesting as cutaneous vasculitis, inflammatory arthropathy, intermittent polyclonal lymphoproliferation, and significant chronic kidney disease and requiring long-term immunosuppressive treatment. Following reduced-intensity conditioning, there was rapid engraftment and expansion of a polyclonal pool of transgene-positive functional T cells and sustained gene marking in myeloid and B-cell lineages up to 20 months of observation. The patient was able to discontinue immunosuppression and exogenous immunoglobulin support, with improvement in vasculitic disease and proinflammatory markers. Autologous gene therapy using a lentiviral vector is a viable strategy for adult WAS patients with severe chronic disease complications and for whom an allogeneic procedure could present an unacceptable risk. This trial was registered at www.clinicaltrials.gov as #NCT01347242. © 2017 by The American Society of Hematology.

  3. Age-dependent changes in cuticular hydrocarbons of larvae in Aldrichina grahami (Aldrich) (Diptera: Calliphoridae).

    PubMed

    Xu, Hong; Ye, Gong-Yin; Xu, Ying; Hu, Cui; Zhu, Guang-Hui

    2014-09-01

    Necrophagous flies, comprising the first wave of insects present in a cadaver, provide a great potential for more accurate determination of the late postmortem interval (PMI) based on their age. Cuticular hydrocarbons (CHs) are a promising age indicator in some insect species, especially for the larvae of necrophagous flies. Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were used to characterize the age-dependent, quantitative changes in CHs of larval Aldrichina grahami (Aldrich) (Diptera: Calliphoridae) at 24°C. The majority of low-molecular-weight alkanes (≤C25) and almost all of the alkenes decreased in abundance with larval development. By contrast, the abundance of high-molecular-weight alkanes of chain length greater than C25 gradually increased with age. For several peaks, including peak 28 (pentacosene a), peak 31 (n-C25), peak 43 (n-C27) and peak 68 (n-C31), a highly significant correlation was found between peak ratio (n-C29 divided by each chromatographic peak) and chronological age of the larvae. A mathematical model, derived from multivariate linear regression analysis, was developed for determining age of the larvae based on age-dependent changes in CHs. The estimated larval age based on the CHs had a good linear correlation with the chronological age (R(2)>0.9). These results indicate that CHs has a great potential for determining the age of fly larvae, and concomitantly for the PMI in forensic investigation.

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

    PubMed

    Natarajan, Rajalaxmi; Barber, Kara; Buckley, Amanda; Cho, Phillip; Egbejimi, Anuoluwapo; Wairkar, Yogesh P

    2015-01-01

    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.

  5. Wiskott-Aldrich syndrome protein deficiency in natural killer and dendritic cells affects antitumor immunity.

    PubMed

    Catucci, Marco; Zanoni, Ivan; Draghici, Elena; Bosticardo, Marita; Castiello, Maria C; Venturini, Massimo; Cesana, Daniela; Montini, Eugenio; Ponzoni, Maurilio; Granucci, Francesca; Villa, Anna

    2014-04-01

    Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency caused by reduced or absent expression of the WAS protein (WASP). WAS patients are affected by microthrombocytopenia, recurrent infections, eczema, autoimmune diseases, and malignancies. Although immune deficiency has been proposed to play a role in tumor pathogenesis, there is little evidence on the correlation between immune cell defects and tumor susceptibility. Taking advantage of a tumor-prone model, we show that the lack of WASP induces early tumor onset because of defective immune surveillance. Consistently, the B16 melanoma model shows that tumor growth and the number of lung metastases are increased in the absence of WASP. We then investigated the in vivo contribution of Was(-/-) NK cells and DCs in controlling B16 melanoma development. We found fewer B16 metastases developed in the lungs of Was(-/-) mice that had received WT NK cells as compared with mice bearing Was(-/-) NK cells. Furthermore, we demonstrated that Was(-/-) DCs were less efficient in inducing NK-cell activation in vitro and in vivo. In summary, for the first time, we demonstrate in in vivo models that WASP deficiency affects resistance to tumor and causes impairment in the antitumor capacity of NK cells and DCs. © 2013 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Gene therapy for Wiskott-Aldrich syndrome--long-term efficacy and genotoxicity.

    PubMed

    Braun, Christian Jörg; Boztug, Kaan; Paruzynski, Anna; Witzel, Maximilian; Schwarzer, Adrian; Rothe, Michael; Modlich, Ute; Beier, Rita; Göhring, Gudrun; Steinemann, Doris; Fronza, Raffaele; Ball, Claudia Regina; Haemmerle, Reinhard; Naundorf, Sonja; Kühlcke, Klaus; Rose, Martina; Fraser, Chris; Mathias, Liesl; Ferrari, Rudolf; Abboud, Miguel R; Al-Herz, Waleed; Kondratenko, Irina; Maródi, László; Glimm, Hanno; Schlegelberger, Brigitte; Schambach, Axel; Albert, Michael Heinrich; Schmidt, Manfred; von Kalle, Christof; Klein, Christoph

    2014-03-12

    Wiskott-Aldrich syndrome (WAS) is characterized by microthrombocytopenia, immunodeficiency, autoimmunity, and susceptibility to malignancies. In our hematopoietic stem cell gene therapy (GT) trial using a γ-retroviral vector, 9 of 10 patients showed sustained engraftment and correction of WAS protein (WASP) expression in lymphoid and myeloid cells and platelets. GT resulted in partial or complete resolution of immunodeficiency, autoimmunity, and bleeding diathesis. Analysis of retroviral insertion sites revealed >140,000 unambiguous integration sites and a polyclonal pattern of hematopoiesis in all patients early after GT. Seven patients developed acute leukemia [one acute myeloid leukemia (AML), four T cell acute lymphoblastic leukemia (T-ALL), and two primary T-ALL with secondary AML associated with a dominant clone with vector integration at the LMO2 (six T-ALL), MDS1 (two AML), or MN1 (one AML) locus]. Cytogenetic analysis revealed additional genetic alterations such as chromosomal translocations. This study shows that hematopoietic stem cell GT for WAS is feasible and effective, but the use of γ-retroviral vectors is associated with a substantial risk of leukemogenesis.

  7. Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients

    PubMed Central

    Pala, Francesca; Morbach, Henner; Castiello, Maria Carmina; Schickel, Jean-Nicolas; Scaramuzza, Samantha; Chamberlain, Nicolas; Cassani, Barbara; Glauzy, Salome; Romberg, Neil; Candotti, Fabio; Aiuti, Alessandro; Bosticardo, Marita; Villa, Anna; Meffre, Eric

    2015-01-01

    Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by microthrombocytopenia, eczema, and high susceptibility to developing tumors and autoimmunity. Recent evidence suggests that B cells may be key players in the pathogenesis of autoimmunity in WAS. Here, we assessed whether WAS protein deficiency (WASp deficiency) affects the establishment of B cell tolerance by testing the reactivity of recombinant antibodies isolated from single B cells from 4 WAS patients before and after gene therapy (GT). We found that pre-GT WASp-deficient B cells were hyperreactive to B cell receptor stimulation (BCR stimulation). This hyperreactivity correlated with decreased frequency of autoreactive new emigrant/transitional B cells exiting the BM, indicating that the BCR signaling threshold plays a major role in the regulation of central B cell tolerance. In contrast, mature naive B cells from WAS patients were enriched in self-reactive clones, revealing that peripheral B cell tolerance checkpoint dysfunction is associated with impaired suppressive function of WAS regulatory T cells. The introduction of functional WASp by GT corrected the alterations of both central and peripheral B cell tolerance checkpoints. We conclude that WASp plays an important role in the establishment and maintenance of B cell tolerance in humans and that restoration of WASp by GT is able to restore B cell tolerance in WAS patients. PMID:26368308

  8. Linkage of the Wiskott-Aldrich syndrome with polymorphic DNA sequences from the human X chromosome

    SciTech Connect

    Peacocke, M.; Siminovitch, K.A.

    1987-05-01

    The Wiskott-Aldrich syndrome (WAS) is one of several human immunodeficiency diseases inherited as an X-linked trait. The location of WAS on the X chromosome is unknown. The authors have studied 10 kindreds segregating for WAS for linkage with cloned, polymorphic DNA markers and have demonstrated significant linkage between WAS and two loci, DXS14 and DXS7, that map to the proximal short arm of the X chromosome. Maximal logarithm of odds (lod scores) for WAS-DXS14 and WAS-DWS7 were 4.29 (at 0 = 0.03) and 4.12 (at 0 = 0.00), respectively. Linkage data between WAS and six markers loci indicate the order of the loci to be (DXYS1-DXS1)-WAS-DXS14-DXS7-(DXS84-OTC). These results suggest that the WAS locus lies within the pericentric region of the X chromosome and provide an initial step toward identifying the WAS gene and improving the genetic counselling WAS families.

  9. The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function

    PubMed Central

    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

  10. WIP is a chaperone for Wiskott–Aldrich syndrome protein (WASP)

    PubMed Central

    de la Fuente, Miguel A.; Sasahara, Yoji; Calamito, Marco; Antón, Inés M.; Elkhal, Abdallah; Gallego, Maria D.; Suresh, Koduru; Siminovitch, Katherine; Ochs, Hans D.; Anderson, Kenneth C.; Rosen, Fred S.; Geha, Raif S.; Ramesh, Narayanaswamy

    2007-01-01

    Wiskott–Aldrich syndrome protein (WASP) is in a complex with WASP-interacting protein (WIP). WASP levels, but not mRNA levels, were severely diminished in T cells from WIP−/− mice and were increased by introduction of WIP in these cells. The WASP binding domain of WIP was shown to protect WASP from degradation by calpain in vitro. Treatment with the proteasome inhibitors MG132 and bortezomib increased WASP levels in T cells from WIP−/− mice and in T and B lymphocytes from two WAS patients with missense mutations (R86H and T45M) that disrupt WIP binding. The calpain inhibitor calpeptin increased WASP levels in activated T and B cells from the WASP patients, but not in primary T cells from the patients or from WIP−/− mice. Despite its ability to increase WASP levels proteasome inhibition did not correct the impaired IL-2 gene expression and low F-actin content in T cells from the R86H WAS patient. These results demonstrate that WIP stabilizes WASP and suggest that it may also be important for its function. PMID:17213309

  11. Lentivirus-based Gene Therapy of Hematopoietic Stem Cells in Wiskott-Aldrich Syndrome

    PubMed Central

    Aiuti, Alessandro; Biasco, Luca; Scaramuzza, Samantha; Ferrua, Francesca; Cicalese, Maria Pia; Baricordi, Cristina; Dionisio, Francesca; Calabria, Andrea; Giannelli, Stefania; Castiello, Maria Carmina; Bosticardo, Marita; Evangelio, Costanza; Assanelli, Andrea; Casiraghi, Miriam; Di Nunzio, Sara; Callegaro, Luciano; Benati, Claudia; Rizzardi, Paolo; Pellin, Danilo; Di Serio, Clelia; Schmidt, Manfred; Von Kalle, Christof; Gardner, Jason; Mehta, Nalini; Neduva, Victor; Dow, David J.; Galy, Anne; Miniero, Roberto; Finocchi, Andrea; Metin, Ayse; Banerjee, Pinaki; Orange, Jordan; Galimberti, Stefania; Valsecchi, Maria Grazia; Biffi, Alessandra; Montini, Eugenio; Villa, Anna; Ciceri, Fabio; Roncarolo, Maria Grazia; Naldini, Luigi

    2015-01-01

    Wiskott-Aldrich Syndrome (WAS) is an inherited immunodeficiency caused by mutations in the gene encoding WASP, a protein regulating the cytoskeleton. Hematopoietic stem/progenitor cell (HSPC) transplants can be curative but, when matched donors are unavailable, infusion of autologous HSPCs modified ex vivo by gene therapy is an alternative approach. We used a lentiviral vector encoding functional WASP to genetically correct HSPCs from three WAS patients and re-infused the cells after reduced-intensity conditioning regimen. All three patients showed stable engraftment of WASP-expressing cells and improvements in platelet counts, immune functions, and clinical score. Vector integration analyses revealed highly polyclonal and multi-lineage haematopoiesis resulting from the gene corrected HSPCs. Lentiviral gene therapy did not induce selection of integrations near oncogenes and no aberrant clonal expansion was observed after 20–32 months. Although extended clinical observation is required to establish long-term safety, lentiviral gene therapy represents a promising treatment for WAS. PMID:23845947

  12. Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: modulatory role of regulatory B cells.

    PubMed

    Bouma, Gerben; Carter, Natalie A; Recher, Mike; Malinova, Dessislava; Adriani, Marsilio; Notarangelo, Luigi D; Burns, Siobhan O; Mauri, Claudia; Thrasher, Adrian J

    2014-09-01

    Patients deficient in the cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASp) are predisposed to varied autoimmunity, suggesting it has an important controlling role in participating cells. IL-10-producing regulatory B (Breg) cells are emerging as important mediators of immunosuppressive activity. In experimental, antigen-induced arthritis WASp-deficient (WASp knockout [WAS KO]) mice developed exacerbated disease associated with decreased Breg cells and regulatory T (Treg) cells, but increased Th17 cells in knee-draining LNs. Arthritic WAS KO mice showed increased serum levels of B-cell-activating factor, while their B cells were unresponsive in terms of B-cell-activating factor induced survival and IL-10 production. Adoptive transfer of WT Breg cells ameliorated arthritis in WAS KO recipients and restored a normal balance of Treg and Th17 cells. Mice with B-cell-restricted WASp deficiency, however, did not develop exacerbated arthritis, despite exhibiting reduced Breg- and Treg-cell numbers during active disease, and Th17 cells were not increased over equivalent WT levels. These findings support a contributory role for defective Breg cells in the development of WAS-related autoimmunity, but demonstrate that functional competence in other regulatory populations can be compensatory. A properly regulated cytoskeleton is therefore important for normal Breg-cell activity and complementation of defects in this lineage is likely to have important therapeutic benefits. © 2014 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. The Mitochondrial Genome of Elodia flavipalpis Aldrich (Diptera: Tachinidae) and the Evolutionary Timescale of Tachinid Flies

    PubMed Central

    Zhao, Zhe; Su, Tian-juan; Chesters, Douglas; Wang, Shi-di; Ho, Simon Y. W.; Zhu, Chao-dong; Chen, Xiao-lin; Zhang, Chun-tian

    2013-01-01

    Tachinid flies are natural enemies of many lepidopteran and coleopteran pests of forests, crops, and fruit trees. In order to address the lack of genetic data in this economically important group, we sequenced the complete mitochondrial genome of the Palaearctic tachinid fly Elodia flavipalpis Aldrich, 1933. Usually found in Northern China and Japan, this species is one of the primary natural enemies of the leaf-roller moths (Tortricidae), which are major pests of various fruit trees. The 14,932-bp mitochondrial genome was typical of Diptera, with 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes. However, its control region is only 105 bp in length, which is the shortest found so far in flies. In order to estimate dipteran evolutionary relationships, we conducted a phylogenetic analysis of 58 mitochondrial genomes from 23 families. Maximum-likelihood and Bayesian methods supported the monophyly of both Tachinidae and superfamily Oestroidea. Within the subsection Calyptratae, Muscidae was inferred as the sister group to Oestroidea. Within Oestroidea, Calliphoridae and Sarcophagidae formed a sister clade to Oestridae and Tachinidae. Using a Bayesian relaxed clock calibrated with fossil data, we estimated that Tachinidae originated in the middle Eocene. PMID:23626734

  14. Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli ulcer formation

    PubMed Central

    Guenin-Macé, Laure; Veyron-Churlet, Romain; Thoulouze, Maria-Isabel; Romet-Lemonne, Guillaume; Hong, Hui; Leadlay, Peter F.; Danckaert, Anne; Ruf, Marie-Thérèse; Mostowy, Serge; Zurzolo, Chiara; Bousso, Philippe; Chrétien, Fabrice; Carlier, Marie-France; Demangel, Caroline

    2013-01-01

    Mycolactone is a diffusible lipid secreted by the human pathogen Mycobacterium ulcerans, which induces the formation of open skin lesions referred to as Buruli ulcers. Here, we show that mycolactone operates by hijacking the Wiskott-Aldrich syndrome protein (WASP) family of actin-nucleating factors. By disrupting WASP autoinhibition, mycolactone leads to uncontrolled activation of ARP2/3-mediated assembly of actin in the cytoplasm. In epithelial cells, mycolactone-induced stimulation of ARP2/3 concentrated in the perinuclear region, resulting in defective cell adhesion and directional migration. In vivo injection of mycolactone into mouse ears consistently altered the junctional organization and stratification of keratinocytes, leading to epidermal thinning, followed by rupture. This degradation process was efficiently suppressed by coadministration of the N-WASP inhibitor wiskostatin. These results elucidate the molecular basis of mycolactone activity and provide a mechanism for Buruli ulcer pathogenesis. Our findings should allow for the rationale design of competitive inhibitors of mycolactone binding to N-WASP, with anti–Buruli ulcer therapeutic potential. PMID:23549080

  15. Spurious case of XX maleness in a patient with a history of Wiskott-Aldrich syndrome.

    PubMed

    Nebesio, Todd D; Torres-Martinez, Wilfredo; Rink, Richard C; Eugster, Erica A

    2011-01-01

    To alert endocrinologists about the potential for karyotype confusion in patients who have undergone bone marrow transplantation. Clinical, laboratory, and imaging data are reported on a young adult male patient who initially presented because of concerns about short stature. An 18-year-old fully virilized male patient with a history of Wiskott-Aldrich syndrome had undergone successful bone marrow transplantation in infancy. The donor was his older sister. Many years later, he underwent evaluation because of short stature and was found to have a 46, XX karyotype. This unexpected finding led to several costly laboratory and imaging studies, as well as a new diagnosis of a disorder of sex development. The patient was referred to our medical center for further evaluation of XX sex reversal. A skin biopsy was eventually performed, which revealed a 46, XY karyotype. This unusual case highlights the fact that a peripheral blood specimen from bone marrow transplant recipients reflects the genetic makeup of the bone marrow donor. Although the cytogenetic changes that occur in recipients of bone marrow transplants are well known to hematologists and oncologists, they are not commonly recognized by other health care providers. Increased awareness of this potential situation in long-term survivors of bone marrow transplantation is needed.

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

    PubMed

    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.

  17. 78 FR 5499 - Manufacturer of Controlled Substances, Notice of Registration; Sigma Aldrich Research...

    Federal Register 2010, 2011, 2012, 2013, 2014

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  1. CrkL is an adapter for Wiskott-Aldrich syndrome protein and Syk.

    PubMed

    Oda, A; Ochs, H D; Lasky, L A; Spencer, S; Ozaki, K; Fujihara, M; Handa, M; Ikebuchi, K; Ikeda, H

    2001-05-01

    Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia are caused by mutations of the WAS protein (WASP) gene. WASP may be involved in the regulation of podosome, an actin-rich dynamic cell adhesion structure formed by various types of cells. The molecular links between WASP and podosomes or other cell adhesion structures are unknown. Platelets express an SH2-SH3 adapter molecule, CrkL, that can directly associate with paxillin, which is localized in podosomes. The hypothesis that CrkL binds to WASP was, therefore, tested. Results from coprecipitation experiments using anti-CrkL and GST-fusion proteins suggest that CrkL binds to WASP through its SH3 domain and that the binding was not affected by WASP tyrosine phosphorylation. The binding of GST-fusion SH3 domain of PSTPIP1 in vitro was also not affected by WASP tyrosine phosphorylation, suggesting that the binding of the SH3 domains to WASP is not inhibited by tyrosine phosphorylation of WASP. Anti-CrkL also coprecipitates a 72-kd protein, which was identified as syk tyrosine kinase, critical for collagen induced-platelet activation. CrkL immunoprecipitates contain kinase-active syk, as evidenced by an in vitro kinase assay. Coprecipitation experiments using GST-fusion CrkL proteins suggest that both SH2 and SH3 domains of CrkL are involved in the binding of CrkL to syk. WASP, CrkL, syk, and paxillin-like Hic-5 incorporated to platelet cytoskeleton after platelet aggregation. Thus, CrkL is a novel molecular adapter for WASP and syk and may potentially transfer these molecules to the cytoskeleton through association with cytoskeletal proteins such as Hic-5.

  2. [The effect of space flight on metabolism: the results of biochemical research in rat experiments on the Kosmos biosatellites].

    PubMed

    Popova, I A; Grigor'ev, A I

    1992-01-01

    Cosmos biosatellites research program was the unique possibility to study the metabolic features influenced by space flight factors. Based on the existing ideas about relationships between some metabolic responses, the state of metabolism and the systems of its control in the rats flown in space was evaluated to differentiate the processes occurred in microgravity, possibly under effect of this factor and during first postflight hours. The biochemical results of studying the rats exposed to space environments during 7, 14, 18.5 and 19.5 days and sacrificed 4-11 h after landing (Cosmos-782, -936, -1129, -1667, -2044 flight) are used. The major portion of data are in line with understanding that after landing when the microgravity-adapted rats again return to 1-g environments they display an acute stress reaction. A postflight stress reaction is manifested itself in a specific way as compared to adequate and well studied model of acute and chronic stress and dictates subsequent metabolic changes. Postflight together with the acute stressful and progressing readaptation shifts the metabolic signs of previous adaptation to microgravity are shown up. In the absence of engineering feasibility to control or record the state of metabolism inflight it can only presupposed what metabolic status is typical of the animals in space environments and that its development is triggered by a decreased secretion of the biologically active growth hormone. This concept is confirmed by the postflight data.

  3. Wiskott-Aldrich syndrome is an important differential diagnosis in male infants with juvenile myelomonocytic leukemialike features.

    PubMed

    Watanabe, Nobuhiro; Yoshimi, Ayami; Kamachi, Yoshiro; Kawabe, Takashi; Muramatsu, Hideki; Matsumoto, Kimikazu; Manabe, Atsushi; Kojima, Seiji; Kato, Koji

    2007-12-01

    A newborn presented with thrombocytopenia at birth and subsequently developed leukocytosis, monocytosis, and mild hepatomegaly. The bone marrow was normocellular with dysplasia and spontaneous granulocyte-monocyte colony formation was demonstrated. These findings fulfilled the diagnostic criteria of juvenile myelomonocytic leukemia. Then he developed atopic dermatitislike eczema, which led to the consideration of Wiskott-Aldrich syndrome (WAS). Lack of intracellular WASP expression and WASP gene mutation confirmed the diagnosis of WAS. After stem cell transplantation, he is alive in good condition with normal WASP expression. WAS should be considered as a differential diagnosis in male infants with juvenile myelomonocytic leukemialike features.

  4. Immunoglobulins and transient paraproteins in sera of patients with the Wiskott-Aldrich syndrome: a follow-up study.

    PubMed Central

    Radl, J; Dooren, L H; Morell, A; Skvaril, F; Vossen, J M; Uittenbogaart, C H

    1976-01-01

    Immunoglobulin levels of individual classes and IgG subclasses and the occurrence of homogeneous immunoglobulins--paraproteins--were studied longitudinally in the sera of three patients with the Wiskott-Aldrich syndrome; Common findings in all three patients were great variations in the immunoglobulin levels, restricted heterogeneity of the immunoglobulins, the frequent appearance of transient homogeneous immunoglobulins and the presence of serum antibodies against bovine milk proteins. A partial and selective deficiency involving mainly the T immune system is postulated as an explanation for these findings. Images Fig. 2 Fig. 3 Fig. 4 PMID:954233

  5. Impact on biochemical research of the discovery of stable isotopes: the outcome of the serendipic meeting of a refugee with the discoverer of heavy isotopes at Columbia University

    SciTech Connect

    Shemin, D.

    1987-03-01

    As late as the 1930s, approaches to biochemical research not only were rather primitive, but a certain amount of mysticism still surrounded the biochemical events that occur in the living cell. To a great extent, this was due to the lack of techniques needed to uncover the subtle reactions in the living cell. In the early 1930s, an accidental meeting of two scientists revolutionized approaches in biochemical studies and led to the scientific explosion in molecular biology that has occurred during the last few decades. The dark political storm in Germany deposited Dr. Rudolf Schoenheimer on the New York shore, where he met Professor Urey, who recently had discovered ''heavy'' hydrogen. Schoenheimer suggested that biological compounds tagged with heavy atoms of hydrogen would enable investigators to follow their metabolic pathways. This intellectual leap revolutionized the thinking and design of experiments and made it possible to uncover the myriad reactions that occur in the living cell.

  6. [Mutation analysis of WASP gene and prenatal diagnosis of Wiskott-Aldrich syndrome].

    PubMed

    Liu, Ning; Shi, Huirong; Kong, Xiangdong; Wu, Qinghua; Xu, Xueju; Bai, Qiaoling; Feng, Yin; Zhao, Zhenhua

    2014-09-01

    Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and an increased incidence of autoimmunity and malignancies. The patients always have a severe clinical phenotype that can result in death if not diagnosed and treated early in life. The treatment of choice with the best outcome is hematopoietic stem cell transplantation, preferably from a matched related donor. But uncertain treatment effect and high treatment cost limit its clinical application. It is the best strategy that avoiding birth of a fetus with defect through prenatal diagnosis at present. This study aimed to analyze the mutation of WASP gene in 4 Chinese families with WAS and to provide prenatal diagnosis for the high-risk fetus. The probands of the four WAS families were all males, one of whom was deceased but had a family history and clinical datas integrated. All the patients were detected with blood routine tests, immunological tests and bone marrow examination. PCR and bilateral direct sequencing of PCR product was carried out in the regions of exon and exon-intron boundaries of WASP gene for 3 probands, 4 mothers and 100 unrelated healthy individuals as control. Prenatal diagnosis was provided for the two fetuses at the first trimester by mutation analysis. Four WASP gene mutations were detected: c.91A > G (p.E31K), c.665C > T (p.R211X), c.397G > A (p.E133K), c.952-953delCC (p. P317fsX18), among which c.952-953delCC (p. P317fsX18) was first reported. Mothers in Family 2, 3 and 4 were carriers of WASP gene mutation, but family 1 was considered as a de-novo mutation. None of the 100 unaffected subjects had the above mutants. Prenatal diagnosis indicated that the fetus in family 2 was male and carried the same mutation as the proband, so the fetus was presumably to be a patient. The parents decided to receive an induced abortion. Following the termination of the pregnancy, the result of gene analysis of the

  7. Altered O-glycan synthesis in lymphocytes from patients with Wiskott- Aldrich syndrome

    PubMed Central

    1991-01-01

    The only molecular defect reported for the X-linked immunodeficiency Wiskott-Aldrich syndrome (WAS) is the abnormal electrophoretic behavior of the major T lymphocyte sialoglycoprotein CD43. Since the 70 to 80 O- linked carbohydrate chains of CD43 are known to influence markedly its electrophoretic mobility, we analyzed the structure and the biosynthesis of O-glycans of CD43 in lymphocytes from patients with WAS. Immunofluorescence analysis with the carbohydrate dependent anti- CD43 antibody T305 revealed that in 10 out of the 12 WAS patients tested increased numbers of T lymphocytes carry on CD43 an epitope which on normal lymphocytes is expressed only after activation. Other activation antigens were absent from WAS lymphocytes. Western blots of WAS cell lysates displayed a high molecular mass form of CD43 which reacted with the T305 antibody and which could be found on in vivo activated lymphocytes but was absent from normal unstimulated lymphocytes. To examine the O-glycan structures, carbohydrate labeled CD43 was immunoprecipitated and the released oligosaccharides identified. WAS lymphocyte CD43 was found to carry predominantly the branched structure NeuNAc alpha 2----3Gal beta 1----3 (NeuNAc alpha 2--- -3Gal beta 1----4G1cNAc beta 1----6) GalNAcOH whereas normal lymphocytes carry the structure NeuNAc alpha 2----3Gal beta 1----3 (NeuNAc alpha 2----6) GalNAcOH. Only after activation NeuNAc alpha 2---- 3Gal beta 1----3 (NeuNAc alpha 2----3Gal beta 1----4GlcNAc beta 1----6) GalNAcOH becomes the principal oligosaccharide on CD43 from normal lymphocytes. Analyzing the six glycosyltransferases involved in the biosynthesis of these O-glycan structures it was found that in WAS lymphocytes high levels of beta 1----6 N-acetyl-glucosaminyl transferase are responsible for the expression of NeuNAc alpha 2---- 3Gal beta 1----3 (NeuNAc alpha 2----3Gal beta 1----4GlcNAc beta 1----6) GalNAcOH on CD43. The gene responsible for WAS has not yet been identified but the results

  8. The UDP-galactose translocator gene is mapped to band Xp11. 23-p11. 22 containing the Wiskott-Aldrich Syndrome Locus

    SciTech Connect

    Hara, Takahiko; Hoshino, Masato; Aoki, Kazuhisa; Ayusawa, Dai; Kawakita, Masao ); Yamauchi, Masatake; Takahashi, Ei-ichi )

    1993-11-01

    The authors have cloned a segment of the human gene encoding UDP-galactose translocator by genetic complementation of its defective mutant in mouse FM3A cells. Chromosome mapping using fluorescent in situ hybridization revealed that the cloned gene hybridized to the Xp11.23-11.23 region of the X chromosome. This region is shared by the locus of Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency disorder, characterized by defective sugar chains on cell surface components. Genetic and phenotypic similarities suggest a possible link between UDP-galactose translocator and the Wiskott-Aldrich syndrome (WAS).

  9. Wasp, the Drosophila Wiskott-Aldrich Syndrome Gene Homologue, Is Required for Cell Fate Decisions Mediated by Notch Signaling

    PubMed Central

    Ben-Yaacov, Sari; Le Borgne, Roland; Abramson, Irit; Schweisguth, Francois; Schejter, Eyal D.

    2001-01-01

    Wiskott-Aldrich syndrome proteins, encoded by the Wiskott-Aldrich syndrome gene family, bridge signal transduction pathways and the microfilament-based cytoskeleton. Mutations in the Drosophila homologue, Wasp (Wsp), reveal an essential requirement for this gene in implementation of cell fate decisions during adult and embryonic sensory organ development. Phenotypic analysis of Wsp mutant animals demonstrates a bias towards neuronal differentiation, at the expense of other cell types, resulting from improper execution of the program of asymmetric cell divisions which underlie sensory organ development. Generation of two similar daughter cells after division of the sensory organ precursor cell constitutes a prominent defect in the Wsp sensory organ lineage. The asymmetric segregation of key elements such as Numb is unaffected during this division, despite the misassignment of cell fates. The requirement for Wsp extends to additional cell fate decisions in lineages of the embryonic central nervous system and mesoderm. The nature of the Wsp mutant phenotypes, coupled with genetic interaction studies, identifies an essential role for Wsp in lineage decisions mediated by the Notch signaling pathway. PMID:11149916

  10. Transformation of 2,4,6-trimethylphenol and furfuryl alcohol, photosensitised by Aldrich humic acids subject to different filtration procedures.

    PubMed

    Minella, Marco; Merlo, Maria Paola; Maurino, Valter; Minero, Claudio; Vione, Davide

    2013-01-01

    Suspended particles in a system made up of Aldrich humic acids (HAs) in water account for about 13% of the total HA mass, 10-11% of the organic carbon and 9-11% of radiation extinction in the UVA region. Extinction would be made up of radiation scattering (less than one third) and absorption (over two thirds). The contribution of particles to the degradation rates of trimethylphenol and furfuryl alcohol (FFA) (probes of triplet states and (1)O(2), respectively) was lower than 10% and possibly negligible. The results indicate that triplet states and (1)O(2) occurring in the solution bulk are mostly produced by the dissolved HA fraction. Experimental data would not exclude production of (1)O(2) in particle hydrophobic cores, unavailable for reaction with FFA. However, the limited to negligible particle fluorescence places an upper limit to particle core photoactivity.

  11. The early activation of memory B cells from Wiskott-Aldrich syndrome patients is suppressed by CD19 downregulation.

    PubMed

    Bai, Xiaoming; Zhang, Yongjie; Huang, Lu; Wang, Jinzhi; Li, Wenyan; Niu, Linlin; Jiang, Hongyan; Dai, Rongxin; Zhou, Lina; Zhang, Zhiyong; Miller, Heather; Song, Wenxia; Zhao, Xiaodong; Liu, Chaohong

    2016-09-29

    Wiskott-Aldrich syndrome (WAS) pediatric patients exhibit a deficiency in humoral immune memory. However, the mechanism by which Wiskott-Aldrich syndrome protein (WASP) regulates the differentiation and activation of memory B cells remains elusive. Here we examine the early activation events of memory B cells from the peripheral blood mononuclear cells of WAS patients and age-matched healthy controls (HCs) using total internal reflection fluorescence microscopy. In response to stimulation through the B-cell receptor (BCR), memory B cells from HCs showed significantly higher magnitudes of BCR clustering and cell spreading than naive B cells from the same individuals. This was associated with increases in CD19 recruitment to the BCR and the activation of its downstream signaling molecule Btk and decreases in FcγRIIB recruitment and the activation of its downstream molecule Src homology 2-containing inositol 5' phosphatase (SHIP). However, these enhanced signaling activities mediated by CD19 and Btk are blocked in memory B cells from WAS patients, whereas the activation of FcγRIIB and SHIP was increased. Although the expression levels of CD19, Btk, and FcγRIIB did not change between CD27(-) and CD27(+) B cells of HCs, the protein and mRNA levels of CD19 but not Btk and FcγRIIB were significantly reduced in both CD27(-) and CD27(+) B cells of WAS patients, compared with those of HCs. Overall, our study suggests that WASP is required for memory B-cell activation, promoting the activation by positive regulating CD19 transcription and CD19 recruitment to the BCR.

  12. B-cell reconstitution after lentiviral vector-mediated gene therapy in patients with Wiskott-Aldrich syndrome.

    PubMed

    Castiello, Maria Carmina; Scaramuzza, Samantha; Pala, Francesca; Ferrua, Francesca; Uva, Paolo; Brigida, Immacolata; Sereni, Lucia; van der Burg, Mirjam; Ottaviano, Giorgio; Albert, Michael H; Grazia Roncarolo, Maria; Naldini, Luigi; Aiuti, Alessandro; Villa, Anna; Bosticardo, Marita

    2015-09-01

    Wiskott-Aldrich syndrome (WAS) is a severe X-linked immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and susceptibility to autoimmunity and lymphomas. Hematopoietic stem cell transplantation is the treatment of choice; however, administration of WAS gene-corrected autologous hematopoietic stem cells has been demonstrated as a feasible alternative therapeutic approach. Because B-cell homeostasis is perturbed in patients with WAS and restoration of immune competence is one of the main therapeutic goals, we have evaluated reconstitution of the B-cell compartment in 4 patients who received autologous hematopoietic stem cells transduced with lentiviral vector after a reduced-intensity conditioning regimen combined with anti-CD20 administration. We evaluated B-cell counts, B-cell subset distribution, B cell-activating factor and immunoglobulin levels, and autoantibody production before and after gene therapy (GT). WAS gene transfer in B cells was assessed by measuring vector copy numbers and expression of Wiskott-Aldrich syndrome protein. After lentiviral vector-mediated GT, the number of transduced B cells progressively increased in the peripheral blood of all patients. Lentiviral vector-transduced progenitor cells were able to repopulate the B-cell compartment with a normal distribution of B-cell subsets both in bone marrow and the periphery, showing a WAS protein expression profile similar to that of healthy donors. In addition, after GT, we observed a normalized frequency of autoimmune-associated CD19(+)CD21(-)CD35(-) and CD21(low) B cells and a reduction in B cell-activating factor levels. Immunoglobulin serum levels and autoantibody production improved in all treated patients. We provide evidence that lentiviral vector-mediated GT induces transgene expression in the B-cell compartment, resulting in ameliorated B-cell development and functionality and contributing to immunologic improvement in patients with WAS. Copyright

  13. Effects of Wiskott-Aldrich Syndrome Protein Deficiency on IL-10-Producing Regulatory B Cells in Humans and Mice.

    PubMed

    Du, H-Q; Zhang, X; An, Y-F; Ding, Y; Zhao, X-D

    2015-06-01

    The Wiskott-Aldrich syndrome protein (WASp) is an important regulator of the actin cytoskeleton and is required for immune cell function. WASp deficiency causes a marked reduction in major mature peripheral B cell subsets, particularly marginal zone (MZ) B cells. We hypothesized that WASp deficiency may also lead to a reduction of regulatory B cells (known as B10 cells) belonging to a novel subset of B cells. And in consideration of the key role of B10 cells play in maintaining peripheral tolerance, we conjectured that a deficit of these cells could contribute to the autoimmunity in patients with Wiskott-Aldrich syndrome (WAS). The effects of WASp deficiency on B10 cells have been reported by only one group, which used an antigen-induced arthritis model. To add more information, we measured the percentage of B10 cells, regulatory T cells (Tregs) and Th1 cells in WASp knockout (WASp KO) mice. We also measured the percentage of B10 cells in patients with WAS by flow cytometry. Importantly, we used the non-induced autoimmune WASp KO mouse model to investigate the association between B10 cell frequency and the Treg/Th1 balance. We found that the percentage of B10 cells was reduced in both mice (steady state and inflammatory state) and in humans and that the lower B10 population correlated with an imbalance in the Treg/Th1 ratio in old WASp KO mice with autoimmune colitis. These findings suggest that WASp plays a crucial role in B10 cell development and that WASp-deficient B10 cells may contribute to autoimmunity in WAS. © 2015 John Wiley & Sons Ltd.

  14. Measures of Biochemical Sociology

    ERIC Educational Resources Information Center

    Snell, Joel; Marsh, Mitchell

    2008-01-01

    In a previous article, the authors introduced a new sub field in sociology that we labeled "biochemical sociology." We introduced the definition of a sociology that encompasses sociological measures, psychological measures, and biological indicators Snell & Marsh (2003). In this article, we want to demonstrate a research strategy that would assess…

  15. Measures of Biochemical Sociology

    ERIC Educational Resources Information Center

    Snell, Joel; Marsh, Mitchell

    2008-01-01

    In a previous article, the authors introduced a new sub field in sociology that we labeled "biochemical sociology." We introduced the definition of a sociology that encompasses sociological measures, psychological measures, and biological indicators Snell & Marsh (2003). In this article, we want to demonstrate a research strategy that would assess…

  16. Biochemical Engineering and Industrial Biotechnology.

    ERIC Educational Resources Information Center

    Moo-Young, Murray

    1986-01-01

    Describes the biochemical engineering and industrial biotechnology programs of the University of Waterloo (Ontario, Canada). Provides descriptions of graduate courses, along with a sample of current research activities. Includes a discussion of the programs' mechanisms for technology transfer. (TW)

  17. Biochemical Engineering and Industrial Biotechnology.

    ERIC Educational Resources Information Center

    Moo-Young, Murray

    1986-01-01

    Describes the biochemical engineering and industrial biotechnology programs of the University of Waterloo (Ontario, Canada). Provides descriptions of graduate courses, along with a sample of current research activities. Includes a discussion of the programs' mechanisms for technology transfer. (TW)

  18. Fractionation of Suwannee River Fulvic Acid and Aldrich Humic Acid on α-Al2O3: Spectroscopic Evidence

    SciTech Connect

    Claret, F.; Schäfer, T; Brevet, J; Reiller, P

    2008-01-01

    Sorptive fractionation of Suwannee River Fulvic Acid (SRFA) and Purified Aldrich Humic Acid (PAHA) on a-Al2O3 at pH 6 was probed in the supernatant using different spectroscopic techniques. Comparison of dissolved organic carbon (DOC) analysis with UV/vis spectrophotometric measurements at 254 nm, including specific UV absorbance (SUVA) calculation, revealed a decrease in chromophoric compounds for the nonsorbed extracts after a 24 h contact time. This fractionation, only observable below a certain ratio between initial number of sites of humic substances and of a-Al2O3, seems to indicate a higher fractionation for PAHA. C(1s) near-edge X-ray absorption fine structure spectroscopy (NEXAFS) confirmed this trend and points to a decrease in phenolic moieties in the supernatant and to an eventual increase in phenolic moieties on the surface. Time-resolved luminescence spectroscopy (TRLS) of Eu(III) as luminescent probe showed a decrease in the ratio between the 5D0?7F2 and 5D0?7F1 transitions for the fractionated organic matter (OM) that is thought to be associated with a lower energy transfer from the OM to Eu(III) due to the loss of polar aromatics. These modifications in the supernatant are a hint for the modification of sorbed humic extracts on the surface.

  19. Gene Correction of iPSCs from a Wiskott-Aldrich Syndrome Patient Normalizes the Lymphoid Developmental and Functional Defects.

    PubMed

    Laskowski, Tamara J; Van Caeneghem, Yasmine; Pourebrahim, Rasoul; Ma, Chao; Ni, Zhenya; Garate, Zita; Crane, Ana M; Li, Xuan Shirley; Liao, Wei; Gonzalez-Garay, Manuel; Segovia, Jose Carlos; Paschon, David E; Rebar, Edward J; Holmes, Michael C; Kaufman, Dan; Vandekerckhove, Bart; Davis, Brian R

    2016-08-09

    Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease caused by mutations in the gene encoding the WAS protein (WASp). Here, induced pluripotent stem cells (iPSCs) were derived from a WAS patient (WAS-iPSC) and the endogenous chromosomal WAS locus was targeted with a wtWAS-2A-eGFP transgene using zinc finger nucleases (ZFNs) to generate corrected WAS-iPSC (cWAS-iPSC). WASp and GFP were first expressed in the earliest CD34(+)CD43(+)CD45(-) hematopoietic precursor cells and later in all hematopoietic lineages examined. Whereas differentiation to non-lymphoid lineages was readily obtained from WAS-iPSCs, in vitro T lymphopoiesis from WAS-iPSC was deficient with few CD4(+)CD8(+) double-positive and mature CD3(+) T cells obtained. T cell differentiation was restored for cWAS-iPSCs. Similarly, defects in natural killer cell differentiation and function were restored on targeted correction of the WAS locus. These results demonstrate that the defects exhibited by WAS-iPSC-derived lymphoid cells were fully corrected and suggests the potential therapeutic use of gene-corrected WAS-iPSCs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Early deficit of lymphocytes in Wiskott–Aldrich syndrome: possible role of WASP in human lymphocyte maturation

    PubMed Central

    PARK, J Y; KOB, M; PRODEUS, A P; ROSEN, F S; SHCHERBINA, A; REMOLD-O'DONNELL, E

    2004-01-01

    Wiskott–Aldrich syndrome (WAS) is an X-linked platelet/immunodeficiency disease. The affected gene encodes WASP, a multidomain protein that regulates cytoskeletal assembly in blood cells. Patients have recurring infections, and their lymphocytes exhibit deficient proliferative responses in vitro. We report an evaluation of peripheral blood lymphocytes of 27 WAS patients, aged one month to 55 years. Whereas NK cells were normal, a significant deficit of T and B lymphocytes was observed. The number of lymphocytes was already decreased in infant patients, suggesting deficient output. Both CD4 and CD8 T lymphocytes were affected; the decrease was most pronounced for naïve T cells. Naïve CD4 lymphocytes of patients showed normal expression of Bcl-2, and Ki-67, and normal survival in vitro, suggesting that their in vivo survival and proliferation are normal. The collective data suggest that the patients’ lymphocyte deficit results from deficient output, likely due to abnormal lymphocyte maturation in the thymus and bone marrow. We propose that WASP plays an important role not only in the function of mature T lymphocytes, but also in the maturation of human T and B lymphocytes and that impaired lymphocyte maturation is central to the aetiology of WAS immunodeficiency. PMID:15030520

  1. Dendritic cell functional improvement in a preclinical model of lentiviral-mediated gene therapy for Wiskott-Aldrich syndrome

    PubMed Central

    Catucci, Marco; Prete, Francesca; Bosticardo, Marita; Castiello, Maria Carmina; Draghici, Elena; Locci, Michela; Roncarolo, Maria Grazia; Aiuti, Alessandro; Benvenuti, Federica; Villa, Anna

    2011-01-01

    Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency caused by the defective expression of the WAS protein (WASP) in hematopoietic cells. It has been shown that dendritic cells (DCs) are functionally impaired in WAS patients and was−/− mice. We have previously demonstrated the efficacy and safety of a murine model of WAS gene therapy (GT), using stem cells transduced with a lentiviral vector. The aim of this study was to investigate whether GT can correct DC defects in was−/− mice. As DCs expressing WASP were detected in the secondary lymphoid organs of the treated mice, we tested the in vitro and in vivo function of bone marrow-derived DCs (BMDCs). The BMDCs showed efficient in vitro uptake of latex beads and Salmonella typhimurium. When BMDCs from the treated mice (GT BMDCs) and the was−/− mice were injected into wild type hosts, we found a higher number of cells that had migrated to the draining lymph nodes compared to mice injected with was−/− BMDCs. Finally, we found that OVA-pulsed GT BMDCs or vaccination with anti-DEC205 OVA fusion protein can efficiently induce antigen-specific T cell activation in vivo. These findings show that WAS GT significantly improves DC function, thus adding new evidence of the preclinical efficacy of lentiviral vector-mediated WAS GT. PMID:22189416

  2. Dendritic cell functional improvement in a preclinical model of lentiviral-mediated gene therapy for Wiskott-Aldrich syndrome.

    PubMed

    Catucci, M; Prete, F; Bosticardo, M; Castiello, M C; Draghici, E; Locci, M; Roncarolo, M G; Aiuti, A; Benvenuti, F; Villa, A

    2012-12-01

    Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency caused by the defective expression of the WAS protein (WASP) in hematopoietic cells. It has been shown that dendritic cells (DCs) are functionally impaired in WAS patients and was(-/-) mice. We have previously demonstrated the efficacy and safety of a murine model of WAS gene therapy (GT), using stem cells transduced with a lentiviral vector (LV). The aim of this study was to investigate whether GT can correct DC defects in was(-/-) mice. As DCs expressing WASP were detected in the secondary lymphoid organs of the treated mice, we tested the in vitro and in vivo function of bone marrow-derived DCs (BMDCs). The BMDCs showed efficient in vitro uptake of latex beads and Salmonella typhimurium. When BMDCs from the treated mice (GT BMDCs) and the was(-/-) mice were injected into wild-type hosts, we found a higher number of cells that had migrated to the draining lymph nodes compared with mice injected with was(-/-) BMDCs. Finally, we found that ovalbumin (OVA)-pulsed GT BMDCs or vaccination of GT mice with anti-DEC205 OVA fusion protein can efficiently induce antigen-specific T-cell activation in vivo. These findings show that WAS GT significantly improves DC function, thus adding new evidence of the preclinical efficacy of LV-mediated WAS GT.

  3. Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function

    PubMed Central

    Dahlberg, Carin; Baptista, Marisa; Moran, Christopher J.; Detre, Cynthia; Keszei, Marton; Eston, Michelle A.; Alt, Frederick W.; Terhorst, Cox; Notarangelo, Luigi D.

    2012-01-01

    The Wiskott-Aldrich syndrome protein (WASP) is a key cytoskeletal regulator of hematopoietic cells. Although WASP-knockout (WKO) mice have aberrant B-cell cytoskeletal responses, B-cell development is relatively normal. We hypothesized that N-WASP, a ubiquitously expressed homolog of WASP, may serve some redundant functions with WASP in B cells. In the present study, we generated mice lacking WASP and N-WASP in B cells (conditional double knockout [cDKO] B cells) and show that cDKO mice had decreased numbers of follicular and marginal zone B cells in the spleen. Receptor-induced activation of cDKO B cells led to normal proliferation but a marked reduction of spreading compared with wild-type and WKO B cells. Whereas WKO B cells showed decreased migration in vitro and homing in vivo compared with wild-type cells, cDKO B cells showed an even more pronounced decrease in the migratory response in vivo. After injection of 2,4,6-trinitrophenol (TNP)–Ficoll, cDKO B cells had reduced antigen uptake in the splenic marginal zone. Despite high basal serum IgM, cDKO mice mounted a reduced immune response to the T cell–independent antigen TNP-Ficoll and to the T cell–dependent antigen TNP–keyhole limpet hemocyanin. Our results reveal that the combined activity of WASP and N-WASP is required for peripheral B-cell development and function. PMID:22411869

  4. Influence of Aldrich humic acid and metal precipitates on survivorship of mayflies (Atalophlebia spp.) to acid mine drainage.

    PubMed

    Holland, Aleicia; Duivenvoorden, Leo J; Kinnear, Susan H W

    2014-03-01

    Humic substances (HS) have been shown to decrease the toxicity of environmental stressors, but knowledge of their ability to influence the toxicity of multiple stressors such as metal mixtures and low pH associated with acid mine drainage (AMD) is still limited. The present study investigated the ability of HS to decrease toxicity of AMD to mayflies (Atalophlebia spp.). The AMD was collected from the Mount Morgan (Mount Morgan, Queensland, Australia) open pit. Mayflies were exposed to concentrations of AMD at 0%, 1%, 2%, 3%, and 4% in the presence of 0 mg/L, 10 mg/L, and 20 mg/L Aldrich humic acid (AHA). A U-shaped response was noted in all AHA treatments, with higher rates of mortality recorded in the 2% and 3% dilutions compared with 4%. This result was linked with increased precipitates in the lower concentrations. A follow-up trial showed significantly higher concentrations of precipitates in the 2% and 3% AMD dilutions in the 0 mg/L AHA treatment and higher precipitates in the 2% AMD, 10 mg/L and 20 mg/L AHA, treatments. Humic substances were shown to significantly increase survival of mayflies exposed to AMD by up to 50% in the 20 mg/L AHA treatment. Humic substances may have led to increased survival after AMD exposure through its ability to influence animal physiology and complex heavy metals. These results are valuable in understanding the ability of HS to influence the toxicity of multiple stressors.

  5. Fractionation of Suwannee River fulvic acid and aldrich humic acid on alpha-Al2O3: spectroscopic evidence.

    PubMed

    Claret, Francis; Schäfer, Thorsten; Brevet, Julien; Reiller, Pascal E

    2008-12-01

    Sorptive fractionation of Suwannee River Fulvic Acid (SRFA) and Purified Aldrich Humic Acid (PAHA) on alpha-Al2O3 at pH 6 was probed in the supernatant using different spectroscopic techniques. Comparison of dissolved organic carbon (DOC) analysis with UV/vis spectrophotometric measurements at 254 nm, including specific UV absorbance (SUVA) calculation, revealed a decrease in chromophoric compounds for the nonsorbed extracts after a 24 h contact time. This fractionation, only observable below a certain ratio between initial number of sites of humic substances and of alpha-Al2O3, seems to indicate a higher fractionation for PAHA. C(1s) near-edge X-ray absorption fine structure spectroscopy (NEXAFS) confirmed this trend and points to a decrease in phenolic moieties in the supernatant and to an eventual increase in phenolic moieties on the surface. Time-resolved luminescence spectroscopy (TRLS) of Eu(III) as luminescent probe showed a decrease in the ratio between the (5)D0-->(7)F2 and (5)D0-->(7)F1 transitions for the fractionated organic matter (OM) that is thought to be associated with a lower energy transfer from the OM to Eu(III) due to the loss of polar aromatics. These modifications in the supernatant are a hint for the modification of sorbed humic extracts on the surface.

  6. Systemic autoimmunity and defective Fas ligand secretion in the absence of the Wiskott-Aldrich syndrome protein

    PubMed Central

    Nikolov, Nikolay P.; Shimizu, Masaki; Cleland, Sophia; Bailey, Daniel; Aoki, Joseph; Strom, Ted; Schwartzberg, Pamela L.; Candotti, Fabio

    2010-01-01

    Autoimmunity is a surprisingly common complication of primary immunodeficiencies, yet the molecular mechanisms underlying this clinical observation are not well understood. One widely known example is provided by Wiskott-Aldrich syndrome (WAS), an X-linked primary immunodeficiency disorder caused by mutations in the gene encoding the WAS protein (WASp) with a high incidence of autoimmunity in affected patients. WASp deficiency affects T-cell antigen receptor (TCR) signaling and T-cell cytokine production, but its role in TCR-induced apoptosis, one of the mechanisms of peripheral immunologic tolerance, has not been investigated. We find that WASp-deficient mice produce autoantibodies and develop proliferative glomerulonephritis with immune complex deposition as they age. We also find that CD4+ T lymphocytes from WASp-deficient mice undergo reduced apoptosis after restimulation through the TCR. While Fas-induced cell death is normal, WASp deficiency affects TCR-induced secretion of Fas ligand (FasL) and other components of secretory granules by CD4+ T cells. These results describe a novel role of WASp in regulating TCR-induced apoptosis and FasL secretion and suggest that WASp-deficient mice provide a good model for the study of autoimmune manifestations of WAS and the development of more specific therapies for these complications. PMID:20457871

  7. Deletion of Wiskott–Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells

    PubMed Central

    Baptista, Marisa A. P.; Keszei, Marton; Oliveira, Mariana; Sunahara, Karen K. S.; Andersson, John; Dahlberg, Carin I. M.; Worth, Austen J.; Liedén, Agne; Kuo, I-Chun; Wallin, Robert P. A.; Snapper, Scott B.; Eidsmo, Liv; Scheynius, Annika; Karlsson, Mikael C. I.; Bouma, Gerben; Burns, Siobhan O.; Forsell, Mattias N. E.; Thrasher, Adrian J.; Nylén, Susanne; Westerberg, Lisa S.

    2016-01-01

    Wiskott–Aldrich syndrome (WAS) is caused by loss-of-function mutations in the WASp gene. Decreased cellular responses in WASp-deficient cells have been interpreted to mean that WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an exception to this concept and show that WASp-deficient dendritic cells have increased activation of Rac2 that support cross-presentation to CD8+ T cells. Using two different skin pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin and increased expansion of IFNγ-producing CD8+ T cells in the draining lymph node and spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8+ T cells at the expense of CD4+ T cells. WASp-deficient dendritic cells induce increased cross-presentation to CD8+ T cells by activating Rac2 that maintains a near neutral pH of phagosomes. Our data reveals an intricate balance between activation of WASp and Rac2 signalling pathways in dendritic cells. PMID:27425374

  8. Neural Wiskott-Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri.

    PubMed Central

    Suzuki, T; Miki, H; Takenawa, T; Sasakawa, C

    1998-01-01

    Shigella, the causative agent of bacillary dysentery, is capable of directing its own movement in the cytoplasm of infected epithelial cells. The bacterial surface protein VirG recruits host components mediating actin polymerization, which is thought to serve as the propulsive force. Here, we show that neural Wiskott-Aldrich syndrome protein (N-WASP), which is a critical target for filopodium formation downstream of Cdc42, is required for assembly of the actin tail generated by intracellular S.flexneri. N-WASP accumulates at the front of the actin tail and is capable of interacting with VirG in vitro and in vivo, a phenomenon that is not observed in intracellular Listeria monocytogenes. The verprolin-homology region in N-WASP was required for binding to the glycine-rich repeats domain of VirG, an essential domain for recruitment of F-actin on intracellular S.flexneri. Overexpression of a dominant-negative N-WASP mutant greatly inhibited formation of the actin tail by intracellular S.flexneri. Furthermore, depletion of N-WASP from Xenopus egg extracts shut off Shigella actin tail assembly, and this was restored upon addition of N-WASP protein, suggesting that N-WASP is a critical host factor for the assembly of the actin tail by intracellular Shigella. PMID:9582270

  9. Lessons from History of Education: The Selected Works of Richard Aldrich. World Library of Educationalists

    ERIC Educational Resources Information Center

    Aldrich, Richard

    2005-01-01

    In the World Library of Educationalists, international scholars themselves compile career-long collections of what they judge to be their finest pieces--extracts from books, key articles, salient research findings, major theoretical and practical contributions--so the world can read them in a single manageable volume. Readers will be able to…

  10. Lessons from History of Education: The Selected Works of Richard Aldrich. World Library of Educationalists

    ERIC Educational Resources Information Center

    Aldrich, Richard

    2005-01-01

    In the World Library of Educationalists, international scholars themselves compile career-long collections of what they judge to be their finest pieces--extracts from books, key articles, salient research findings, major theoretical and practical contributions--so the world can read them in a single manageable volume. Readers will be able to…

  11. Comparison of ZFNs versus CRISPR specific nucleases for genome edition of the Wiskott-Aldrich Syndrome locus.

    PubMed

    Gutierrez-Guerrero, Alejandra; Sanchez-Hernandez, Sabina; Galvani, Giuseppe; Pinedo-Gomez, Javier; Sanchez-Gilabert, Almudena; Martin-Guerra, Rocio; Cobo, Marien; Gregory, Philip; Holmes, Michael; Benabdellah, Karim; Martin, Francisco

    2017-09-19

    Primary immunodeficiencies (PID), including Wiskott-Aldrich syndrome (WAS), are a main target for genome editing (GE) strategies using specific nucleases (SNs) since a small number of corrected hematopoietic stem cells (HSCs) could cure patients. In this work, we have designed different WAS gene-specific CRISPR/Cas9 systems and compared their efficiency and specificity with homodimeric and heterodimeric WAS-specific Zinc Finger Nucleases (ZFNs) using K562 cells as a cellular model and plasmid nucleofection or integrative-deficient Lentiviral Vectors (IDLVs) for delivery. The different CRISPR/Cas9 and ZFNs SNs showed similar efficiency using plasmid nucleofection for delivery. However, dual IDLVs expressing ZFNs were more efficient than dual IDLVs expressing Cas9 and gRNA or that all-in-one IDLVs, expressing Cas9 and gRNA in the same vector. The specificity of heterodimeric ZFNs and CRISPR/Cas9, measured by increments in γH2AX foci formation in WAS-edited cells, was very similar between each other and both outperformed homodimeric ZFNs, independently of the delivery system used. Interestingly, we showed that delivery of SNs using IDLVs is more efficient and less genotoxic than plasmid nucleofection. We also showed a similar behavior of heterodimeric ZFNs and CRISPR/Cas9 for Homology-Directed (HD) gene knock-in strategies, with 88% and 83% of the donors inserted in the WAS locus respectively while using homodimeric ZFNs only 45% of the insertions were on target. In summary, our data indicates that CRISPR/Cas9 and heterodimeric ZFNs are both good alternatives to further develop SNs-based gene therapy strategies for WAS. However IDLVs delivery of WAS-specific heterodimeric ZFNs was the best option of all systems compared in this study.

  12. Altered expression of leucocyte sialoglycoprotein in Wiskott-Aldrich syndrome is associated with a specific defect in O-glycosylation.

    PubMed

    Greer, W L; Higgins, E; Sutherland, D R; Novogrodsky, A; Brockhausen, I; Peacocke, M; Rubin, L A; Baker, M; Dennis, J W; Siminovitch, K A

    1989-09-01

    The Wiskott-Aldrich syndrome (WAS) is an X-linked immune deficiency disorder characterized clinically by both lymphocyte and platelet dysfunction. Studies of WAS T lymphocytes have revealed deficient or defective cell surface expression of the highly O-glycosylated leucocyte sialoglycoprotein CD43. To further elucidate the basis for, and functional relevance of, CD43 modifications on WAS lymphocytes, we have studied lymphocytes from two WAS patients with regard to membrane glycoprotein profile and mitogen-induced proliferative responses. CD43 was found to be either absent or altered in size on peripheral blood lymphocytes and lectin-stimulated T cells from both patients. Compared with control cells, the WAS lymphocytes displayed reduced, but measurable proliferative responses to lectins and neuraminidase/galactose oxidase, and virtually no response to periodate, a mitogenic agent which targets sialic acid residues on membrane glycoproteins such as CD43. Analysis of activities of three glycosyltransferases involved in O-glycosylation revealed marked reduction in the level of activity of UDP-N-acetylglucosamine: Gal beta 1-3GalNAc-R beta-1,6-N-acetylglucosamine (beta-1,6-GlcNAc) transferase in one WAS patient and no detectable activity of this enzyme in a second. beta-1,6-GlcNAc transferase activity has recently been shown to increase during T cell activation coincident with changes in the O-linked glycans on CD43. A selective reduction of this glycosyltransferase in WAS lymphocytes suggests that O-linked oligosaccharides may be important to the structure of membrane glycoproteins involved in lymphocyte activation.

  13. Two sisters with clinical diagnosis of Wiskott-Aldrich Syndrome: Is the condition in the family autosomal recessive?

    SciTech Connect

    Kondoh, T.; Hayashi, K.; Matsumoto, T.

    1995-10-09

    We report two sisters in a family representing manifestations of Wiskott-Aldrich syndrome (WAS), an X-linked immunodeficiency disorder. An elder sister had suffered from recurrent infections, small thrombocytopenic petechiae, purpura, and eczema for 7 years. The younger sister had the same manifestations as the elder sister`s for a 2-year period, and died of intracranial bleeding at age 2 years. All the laboratory data of the two patients were compatible with WAS, although they were females. Sialophorin analysis with the selective radioactive labeling method of this protein revealed that in the elder sister a 115-KD band that should be specific for sialophorin was reduced in quantity, and instead an additional 135-KD fragment was present as a main band. Polymerase chain reaction (PCR) analysis of the sialophorin gene and single-strand conformation polymorphism (SSCP) analysis of the PCR product demonstrated that there were no detectable size-change nor electrophoretic mobility change in the DNA from both patients. The results indicated that their sialophorin gene structure might be normal. Studies on the mother-daughter transmission of X chromosome using a pERT84-MaeIII polymorphic marker mapped at Xp21 and HPRT gene polymorphism at Xq26 suggested that each sister had inherited a different X chromosome from the mother. Two explanations are plausible for the occurrence of the WAS in our patients: the WAS in the patients is attributable to an autosomal gene mutation which may regulate the sialophorin gene expression through the WAS gene, or, alternatively, the condition in this family is an autosomal recessive disorder separated etiologically from the X-linked WAS. 17 refs., 6 figs., 1 tab.

  14. Researchers Hooked on Teaching. Noted Scholars Discuss the Synergies of Teaching and Research. Foundations for Organizational Science Series.

    ERIC Educational Resources Information Center

    Andre, Rae, Ed.; Frost, Peter J., Ed.

    This collection of 19 essays is organized into a narrative of the teaching-research dilemma. The essays include: (1) "Struggling With Balance" (Cynthia V. Fukami); (2) "My Career as a Teacher: Promise, Failure, Redemption" (Howard E. Aldrich); (3) "Teaching and Research: A Puzzling Dichotomy" (Barbara A. Gutek); (4)…

  15. Researchers Hooked on Teaching. Noted Scholars Discuss the Synergies of Teaching and Research. Foundations for Organizational Science Series.

    ERIC Educational Resources Information Center

    Andre, Rae, Ed.; Frost, Peter J., Ed.

    This collection of 19 essays is organized into a narrative of the teaching-research dilemma. The essays include: (1) "Struggling With Balance" (Cynthia V. Fukami); (2) "My Career as a Teacher: Promise, Failure, Redemption" (Howard E. Aldrich); (3) "Teaching and Research: A Puzzling Dichotomy" (Barbara A. Gutek); (4)…

  16. Narrowing the candidate interval of the Wiskott-Aldrich syndrome by a proximal recombination event detected by linkage analysis and X inactivation study

    SciTech Connect

    Schindelhaur, D.; Bader, I.; Golla, A.

    1994-09-01

    The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency combined with thrombocytopenia in which the molecular defect is still unknown. Initial linkage data placed the WAS gene between TIMP and the marker DXS255 in Xp11.23 to Xp11.22. As no recombination was detected between the disease locus closely linked to DXS255 and the marker loci OATL1, SYP and TFE3, the position of WAS relative to these polymorphic loci could not yet be determined. In this study, further segregation analysis has been performed using additional (CA)n repeats DXS1367, DXS6616 and DXS1126. While DXS1367 and DXS6616 could be mapped adjacent to OATL1, location of DXS1126 between OATL1 and TFE3 is demonstrated. In a WAS pedigree of three generations (4 affected males, 10 obligate female carriers, 7 non-carriers) we observed a recombination event between the disease and the locus TIMP, DXSS1367, and DXS6616 in a patient manifesting WAS and the daughter of his female cousin. The carrier status of the female relative was confirmed or excluded by X inactivation analysis. No recombination was detected by the marker DXS6616 containing the zinc finger genes ZNF21 and ZNF81 as a candidate region of the Wiskott-Aldrich syndrome and narrows the boundaries to an interval bracketed by DXS6616 and DXS255. In addition, the current results identify the DXS1367 probe as a useful diagnostic marker for indirect genotype analysis of the Wiskott-Aldrich syndrome.

  17. Nuclear Role of WASp in the Pathogenesis of Dysregulated TH1 Immunity in Human Wiskott-Aldrich Syndrome

    PubMed Central

    Taylor, Matthew D.; Sadhukhan, Sanjoy; Kottangada, Ponnappa; Ramgopal, Archana; Sarkar, Koustav; D’Silva, Sheryl; Selvakumar, Annamalai; Candotti, Fabio; Vyas, Yatin M.

    2010-01-01

    The clinical symptomatology in the X-linked Wiskott-Aldrich syndrome (WAS), a combined immunodeficiency and autoimmune disease resulting from WAS protein (WASp) deficiency, reflects the underlying coexistence of an impaired T helper 1 (TH1) immunity alongside intact TH2 immunity. This suggests a role for WASp in patterning TH subtype immunity, yet the molecular basis for the TH1-TH2 imbalance in human WAS is unknown. We have discovered a nuclear role for WASp in the transcriptional regulation of the TH1 regulator gene TBX21 at the chromatin level. In primary TH1-differentiating cells, a fraction of WASp is found in the nucleus, where it is recruited to the proximal promoter locus of the TBX21 gene, but not to the core promoter of GATA3 (a TH2 regulator gene) or RORc (a TH17 regulator gene). Genome-wide mapping demonstrates association of WASp in vivo with the gene-regulatory network that orchestrates TH1 cell fate choice in the human TH cell genome. Functionally, nuclear WASp associates with H3K4 trimethyltransferase [RBBP5 (retinoblastoma-binding protein 5)] and H3K9/H3K36 tridemethylase [JMJD2A (Jumonji domain-containing protein 2A)] proteins, and their enzymatic activity in vitro and in vivo is required for achieving transcription-permissive chromatin dynamics at the TBX21 proximal promoter in primary differentiating TH1 cells. During TH1 differentiation, the loss of WASp accompanies decreased enrichment of RBBP5 and, in a subset of WAS patients, also of filamentous actin at the TBX21 proximal promoter locus. Accordingly, human WASp-deficient TH cells, from natural mutation or RNA interference–mediated depletion, demonstrate repressed TBX21 promoter dynamics when driven under TH1-differentiating conditions. These chromatin derangements accompany deficient T-BET messenger RNA and protein expression and impaired TH1 function, defects that are ameliorated by reintroducing WASp. Our findings reveal a previously unappreciated role of WASp in the epigenetic control

  18. Wiskott-Aldrich syndrome in a girl caused by heterozygous WASP mutation and extremely skewed X-chromosome inactivation: a novel association with maternal uniparental isodisomy 6.

    PubMed

    Takimoto, Tomohito; Takada, Hidetoshi; Ishimura, Masataka; Kirino, Makiko; Hata, Kenichiro; Ohara, Osamu; Morio, Tomohiro; Hara, Toshiro

    2015-01-01

    Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema and immune deficiency, caused primarily by mutations in the WASP (Wiskott-Aldrich syndrome protein) gene. Female carriers are usually asymptomatic because of the preferential activation of the normal, nonmutated X-chromosome in their hematopoietic cells. We report our observations of a female child with WAS, who displayed symptoms of congenital thrombocytopenia. DNA sequencing analysis of the WASP gene revealed a heterozygous nonsense mutation in exon 10. The expressions of WASP and normal WASP mRNA were defective. We found preferential inactivation of the X-chromosome on which wild-type WASP was located. Single-nucleotide polymorphism microarray testing and the analysis of the polymorphic variable number of tandem repeat regions revealed maternal uniparental isodisomy of chromosome 6 (UPD6). Our results underscore the importance of WASP evaluation in females with congenital thrombocytopenia and suggest that UPD6 might be related to the pathophysiology of nonrandom X-chromosome inactivation.

  19. The mouse homolog of the Wiskott-Aldrich syndrome protein (WASP) gene is highly conserved and maps near the scurfy (sf) mutation on the X chromosome

    SciTech Connect

    Derry, J.M.J.; Wiedemann, P.; Wang, Y.; Kerns, J.A.; Lemahieu, V.; Francke, U.

    1995-09-20

    The mouse WASP gene, the homolog of the gene mutation in Wiskott-Aldrich syndrome, has been isolated and sequenced. The predicted amino acid sequence is 86% identical to human WASP sequence. A distinct feature of the mouse gene is an expanded polymorphic GGA trinucleotide repeat that codes for polyglycine and varies from 15 to 17 triplets in Mus musculus strains. The genomic structure of the mouse gene closely resembles the human with respect to exon-intron positions and intron lengths. The mouse WASP gene is expressed as an {approx}2.4-kb mRNA in thymus and spleen. Chromosomal mapping in an interspecific M. musculus/M. spretus backcross placed in the WASP locus near the centromere of the mouse X chromosome, inseparable form Gata1, Tcfe3, and scurfy (sf). This localization makes WASP a candidate for involvement in scurfy, a T cell-mediated fatal lymphoreticular disease of mice that has previously been proposed as a mouse homolog of Wiskott-Aldrich syndrome. Northern analysis of sf tissue samples indicated the presence of a consequence of lymphocytic infiltration, but no abnormalities in the amount or size of mRNA present. 34 refs., 5 figs.

  20. A Program on Biochemical and Biomedical Engineering.

    ERIC Educational Resources Information Center

    San, Ka-Yiu; McIntire, Larry V.

    1989-01-01

    Presents an introduction to the Biochemical and Biomedical Engineering program at Rice University. Describes the development of the academic and enhancement programs, including organizational structure and research project titles. (YP)

  1. A Program on Biochemical and Biomedical Engineering.

    ERIC Educational Resources Information Center

    San, Ka-Yiu; McIntire, Larry V.

    1989-01-01

    Presents an introduction to the Biochemical and Biomedical Engineering program at Rice University. Describes the development of the academic and enhancement programs, including organizational structure and research project titles. (YP)

  2. Biochemical transformation of coals

    DOEpatents

    Lin, M.S.; Premuzic, E.T.

    1999-03-23

    A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed. 7 figs.

  3. Biochemical transformation of coals

    DOEpatents

    Lin, Mow S.; Premuzic, Eugene T.

    1999-03-23

    A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed.

  4. Biochemical regulators in cardiac hypertrophy.

    PubMed

    Kölbel, F; Schreiber, V

    1983-01-01

    In recent years research has shown that muscle is capable of reacting to mechanical stimuli by altering biochemical processes. Myocardium is probably the source of a biochemical factor, or factors which activate myocardial protein synthesis. In experimentally induced cardiac hypertrophy adaptive alterations have been shown to occur not only in the adrenal medulla but also in the adrenal cortex. Finally, detection of cross reactivity between digitalis glycosides and a number of steroid hormones has succeeded. We assume that such cross reactivity indicates the existence of an endogenic factor of steroid character, which is produced in the adrenal gland and functions as an endogenic cardiotonic agent. During experimental cardiac hypertrophy its synthesis is possibly increased. We propose the term "endocardin" or "endocardiotonin" for this agent.

  5. Biochemical Engineering Fundamentals

    ERIC Educational Resources Information Center

    Bailey, J. E.; Ollis, D. F.

    1976-01-01

    Discusses a biochemical engineering course that is offered as part of a chemical engineering curriculum and includes topics that influence the behavior of man-made or natural microbial or enzyme reactors. (MLH)

  6. IL-2 in the tumor microenvironment is necessary for Wiskott-Aldrich syndrome protein deficient NK cells to respond to tumors in vivo

    PubMed Central

    Kritikou, Joanna S.; Dahlberg, Carin I. M.; Baptista, Marisa A. P.; Wagner, Arnika K.; Banerjee, Pinaki P.; Gwalani, Lavesh Amar; Poli, Cecilia; Panda, Sudeepta K.; Kärre, Klas; Kaech, Susan M.; Wermeling, Fredrik; Andersson, John; Orange, Jordan S.; Brauner, Hanna; Westerberg, Lisa S.

    2016-01-01

    To kill target cells, natural killer (NK) cells organize signaling from activating and inhibitory receptors to form a lytic synapse. Wiskott-Aldrich syndrome (WAS) patients have loss-of-function mutations in the actin regulator WASp and suffer from immunodeficiency with increased risk to develop lymphoreticular malignancies. NK cells from WAS patients fail to form lytic synapses, however, the functional outcome in vivo remains unknown. Here, we show that WASp KO NK cells had decreased capacity to degranulate and produce IFNγ upon NKp46 stimulation and this was associated with reduced capacity to kill MHC class I-deficient hematopoietic grafts. Pre-treatment of WASp KO NK cells with IL-2 ex vivo restored degranulation, IFNγ production, and killing of MHC class I negative hematopoietic grafts. Moreover, WASp KO mice controlled growth of A20 lymphoma cells that naturally produced IL-2. WASp KO NK cells showed increased expression of DNAM-1, LAG-3, and KLRG1, all receptors associated with cellular exhaustion and NK cell memory. NK cells isolated from WAS patient spleen cells showed increased expression of DNAM-1 and had low to negative expression of CD56, a phenotype associated with NK cells exhaustion. Finally, in a cohort of neuroblastoma patients we identified a strong correlation between WASp, IL-2, and patient survival. PMID:27477778

  7. Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and colocalizes with actin to NK cell-activating immunologic synapses

    NASA Astrophysics Data System (ADS)

    Orange, Jordan S.; Ramesh, Narayanaswamy; Remold-O'Donnell, Eileen; Sasahara, Yoji; Koopman, Louise; Byrne, Michael; Bonilla, Francisco A.; Rosen, Fred S.; Geha, Raif S.; Strominger, Jack L.

    2002-08-01

    The Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disorder caused by a mutation in WAS protein (WASp) that results in defective actin polymerization. Although the function of many hematopoietic cells requires WASp, the specific expression and function of this molecule in natural killer (NK) cells is unknown. Here, we report that WAS patients have increased percentages of peripheral blood NK cells and that fresh enriched NK cells from two patients with a WASp mutation have defective cytolytic function. In normal NK cells, WASp was expressed and localized to the activating immunologic synapse (IS) with filamentous actin (F-actin). Perforin also localized to the NK cell-activating IS but at a lesser frequency than F-actin and WASp. The accumulation of F-actin and WASp at the activating IS was decreased significantly in NK cells that had been treated with the inhibitor of actin polymerization, cytochalasin D. NK cells from WAS patients lacked expression of WASp and accumulated F-actin at the activating IS infrequently. Thus, WASp has an important function in NK cells. In patients with WASp mutations, the resulting NK cell defects are likely to contribute to their disease.

  8. Abelson Interactor 1 (Abi1) and Its Interaction with Wiskott-Aldrich Syndrome Protein (Wasp) Are Critical for Proper Eye Formation in Xenopus Embryos*

    PubMed Central

    Singh, Arvinder; Winterbottom, Emily F.; Ji, Yon Ju; Hwang, Yoo-Seok; Daar, Ira O.

    2013-01-01

    Abl interactor 1 (Abi1) is a scaffold protein that plays a central role in the regulation of actin cytoskeleton dynamics as a constituent of several key protein complexes, and homozygous loss of this protein leads to embryonic lethality in mice. Because this scaffold protein has been shown in cultured cells to be a critical component of pathways controlling cell migration and actin regulation at cell-cell contacts, we were interested to investigate the in vivo role of Abi1 in morphogenesis during the development of Xenopus embryos. Using morpholino-mediated translation inhibition, we demonstrate that knockdown of Abi1 in the whole embryo, or specifically in eye field progenitor cells, leads to disruption of eye morphogenesis. Moreover, signaling through the Src homology 3 domain of Abi1 is critical for proper movement of retinal progenitor cells into the eye field and their appropriate differentiation, and this process is dependent upon an interaction with the nucleation-promoting factor Wasp (Wiskott-Aldrich syndrome protein). Collectively, our data demonstrate that the Abi1 scaffold protein is an essential regulator of cell movement processes required for normal eye development in Xenopus embryos and specifically requires an Src homology 3 domain-dependent interaction with Wasp to regulate this complex morphogenetic process. PMID:23558677

  9. Structures of actin-bound Wiskott-Aldrich syndrome protein homology 2 (WH2) domains of Spire and the implication for filament nucleation

    PubMed Central

    Ducka, Anna M.; Joel, Peteranne; Popowicz, Grzegorz M.; Trybus, Kathleen M.; Schleicher, Michael; Noegel, Angelika A.; Huber, Robert; Holak, Tad A.; Sitar, Tomasz

    2010-01-01

    Three classes of proteins are known to nucleate new filaments: the Arp2/3 complex, formins, and the third group of proteins that contain ca. 25 amino acid long actin-binding Wiskott-Aldrich syndrome protein homology 2 domains, called the WH2 repeats. Crystal structures of the complexes between the actin-binding WH2 repeats of the Spire protein and actin were determined for the Spire single WH2 domain D, the double (SpirCD), triple (SpirBCD), quadruple (SpirABCD) domains, and an artificial Spire WH2 construct comprising three identical D repeats (SpirDDD). SpirCD represents the minimal functional core of Spire that can nucleate actin filaments. Packing in the crystals of the actin complexes with SpirCD, SpirBCD, SpirABCD, and SpirDDD shows the presence of two types of assemblies, “side-to-side” and “straight-longitudinal,” which can serve as actin filament nuclei. The principal feature of these structures is their loose, open conformations, in which the sides of actins that normally constitute the inner interface core of a filament are flipped inside out. These Spire structures are distant from those seen in the filamentous nuclei of Arp2/3, formins, and in the F-actin filament. PMID:20538977

  10. The nucleotide switch in Cdc42 modulates coupling between the GTPase-binding and allosteric equilibria of Wiskott–Aldrich syndrome protein

    PubMed Central

    Leung, Daisy W.; Rosen, Michael K.

    2005-01-01

    The GTP/GDP nucleotide switch in Ras superfamily GTPases generally involves differential affinity toward downstream effectors, with the GTP-bound state having a higher affinity for effector than the GDP-bound state. We have developed a quantitative model of allosteric regulation of the Wiskott–Aldrich syndrome protein (WASP) by the Rho GTPase Cdc42 to better understand how GTPase binding is coupled to effector activation. The model accurately predicts WASP affinity for Cdc42, activity toward Arp2/3 complex, and activation by Cdc42 as functions of a two-state allosteric equilibrium in WASP. The ratio of GTPase affinities for the inactive and active states of WASP is appreciably larger for Cdc42–GTP than for Cdc42–GDP. The greater ability to distinguish between the two states of WASP makes Cdc42–GTP a full WASP agonist, whereas Cdc42–GDP is only a partial agonist. Thus, the nucleotide switch controls not only the affinity of Cdc42 for its effector but also the efficiency of coupling between the Cdc42-binding and allosteric equilibria in WASP. This effect can ensure high fidelity and specificity in Cdc42 signaling in crowded membrane environments. PMID:15821030

  11. Signalling to actin assembly via the WASP (Wiskott-Aldrich syndrome protein)-family proteins and the Arp2/3 complex.

    PubMed Central

    Millard, Thomas H; Sharp, Stewart J; Machesky, Laura M

    2004-01-01

    The assembly of a branched network of actin filaments provides the mechanical propulsion that drives a range of dynamic cellular processes, including cell motility. The Arp2/3 complex is a crucial component of such filament networks. Arp2/3 nucleates new actin filaments while bound to existing filaments, thus creating a branched network. In recent years, a number of proteins that activate the filament nucleation activity of Arp2/3 have been identified, most notably the WASP (Wiskott-Aldrich syndrome protein) family. WASP-family proteins activate the Arp2/3 complex, and consequently stimulate actin assembly, in response to extracellular signals. Structural studies have provided a significant refinement in our understanding of the molecular detail of how the Arp2/3 complex nucleates actin filaments. There has also been much progress towards an understanding of the complicated signalling processes that regulate WASP-family proteins. In addition, the use of gene disruption in a number of organisms has led to new insights into the specific functions of individual WASP-family members. The present review will discuss the Arp2/3 complex and its regulators, in particular the WASP-family proteins. Emphasis will be placed on recent developments in the field that have furthered our understanding of actin dynamics and cell motility. PMID:15040784

  12. Sorption of Aldrich humic acid onto hematite: insights into fractionation phenomena by electrospray ionization with quadrupole time-of-flight mass spectrometry.

    PubMed

    Reiller, Pascal; Amekraz, Badia; Moulin, Christophe

    2006-04-01

    Sorption induced fractionation of purified Aldrich humic acid (PAHA) on hematite is studied through the modification of electrospray ionization (ESI) quadrupole time-of-flight (QToF) mass spectra of supernatants from retention experiments. The ESI mass spectra show an increase of the "mean molecular masses" of the molecules that constitutes humic aggregates. The low molecular weight fraction (LMWF; m/z < or = 600 Da) is preferentially sorbed compared to two other fractions. The resolution provided by ESI-QToF mass spectrometer in the low-mass range provided evidence of further fractionation induced by sorption within the LMWF. Among the two latter fractions, the high molecular weight fraction (HMWF; m/z approximately 1700 Da) seems to be more prone to sorption compared to the intermediate molecular weight fraction (IMWF; m/z approximately 900 Da). The IMWF seems to be more hydrophilic as it should be richer in O, N, and alkyl C from the proportion of even mass, and poorer in aromatic structures from mass defect analysis in ESI mass spectra.

  13. B cell–intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice

    PubMed Central

    Recher, Mike; Burns, Siobhan O.; de la Fuente, Miguel A.; Volpi, Stefano; Dahlberg, Carin; Walter, Jolan E.; Moffitt, Kristin; Mathew, Divij; Honke, Nadine; Lang, Philipp A.; Patrizi, Laura; Falet, Hervé; Keszei, Marton; Mizui, Masayuki; Csizmadia, Eva; Candotti, Fabio; Nadeau, Kari; Bouma, Gerben; Delmonte, Ottavia M.; Frugoni, Francesco; Fomin, Angela B. Ferraz; Buchbinder, David; Lundequist, Emma Maria; Massaad, Michel J.; Tsokos, George C.; Hartwig, John; Manis, John; Terhorst, Cox; Geha, Raif S.; Snapper, Scott; Lang, Karl S.; Malley, Richard; Westerberg, Lisa

    2012-01-01

    Wiskott Aldrich syndrome (WAS) is caused by mutations in the WAS gene that encodes for a protein (WASp) involved in cytoskeleton organization in hematopoietic cells. Several distinctive abnormalities of T, B, and natural killer lymphocytes; dendritic cells; and phagocytes have been found in WASp-deficient patients and mice; however, the in vivo consequence of WASp deficiency within individual blood cell lineages has not been definitively evaluated. By conditional gene deletion we have generated mice with selective deficiency of WASp in the B-cell lineage (B/WcKO mice). We show that this is sufficient to cause a severe reduction of marginal zone B cells and inability to respond to type II T-independent Ags, thereby recapitulating phenotypic features of complete WASp deficiency. In addition, B/WcKO mice showed prominent signs of B-cell dysregulation, as indicated by an increase in serum IgM levels, expansion of germinal center B cells and plasma cells, and elevated autoantibody production. These findings are accompanied by hyperproliferation of WASp-deficient follicular and germinal center B cells in heterozygous B/WcKO mice in vivo and excessive differentiation of WASp-deficient B cells into class-switched plasmablasts in vitro, suggesting that WASp-dependent B cell–intrinsic mechanisms critically contribute to WAS-associated autoimmunity. PMID:22302739

  14. Biochemical upgrading of oils

    DOEpatents

    Premuzic, E.T.; Lin, M.S.

    1999-01-12

    A process for biochemical conversion of heavy crude oils is provided. The process includes contacting heavy crude oils with adapted biocatalysts. The resulting upgraded oil shows, a relative increase in saturated hydrocarbons, emulsions and oxygenates and a decrease in compounds containing organic sulfur, organic nitrogen and trace metals. Adapted microorganisms which have been modified under challenged growth processes are also disclosed. 121 figs.

  15. Biochemical upgrading of oils

    DOEpatents

    Premuzic, Eugene T.; Lin, Mow S.

    1999-01-12

    A process for biochemical conversion of heavy crude oils is provided. The process includes contacting heavy crude oils with adapted biocatalysts. The resulting upgraded oil shows, a relative increase in saturated hydrocarbons, emulsions and oxygenates and a decrease in compounds containing in organic sulfur, organic nitrogen and trace metals. Adapted microorganisms which have been modified under challenged growth processes are also disclosed.

  16. Biochemical Education in Brazil.

    ERIC Educational Resources Information Center

    Vella, F.

    1988-01-01

    Described are discussions held concerning the problems of biochemical education in Brazil at a meeting of the Sociedade Brazileira de Bioquimica in April 1988. Also discussed are other visits that were made to universities in Brazil. Three major recommendations to improve the state of biochemistry education in Brazil are presented. (CW)

  17. Nanoparticles as biochemical sensors

    PubMed Central

    El-Ansary, Afaf; Faddah, Layla M

    2010-01-01

    There is little doubt that nanoparticles offer real and new opportunities in many fields, such as biomedicine and materials science. Such particles are small enough to enter almost all areas of the body, including cells and organelles, potentially leading to new approaches in nanomedicine. Sensors for small molecules of biochemical interest are of critical importance. This review is an attempt to trace the use of nanomaterials in biochemical sensor design. The possibility of using nanoparticles functionalized with antibodies as markers for proteins will be elucidated. Moreover, capabilities and applications for nanoparticles based on gold, silver, magnetic, and semiconductor materials (quantum dots), used in optical (absorbance, luminescence, surface enhanced Raman spectroscopy, surface plasmon resonance), electrochemical, and mass-sensitive sensors will be highlighted. The unique ability of nanosensors to improve the analysis of biochemical fluids is discussed either through considering the use of nanoparticles for in vitro molecular diagnosis, or in the biological/biochemical analysis for in vivo interaction with the human body. PMID:24198472

  18. Biochemical Education in Brazil.

    ERIC Educational Resources Information Center

    Vella, F.

    1988-01-01

    Described are discussions held concerning the problems of biochemical education in Brazil at a meeting of the Sociedade Brazileira de Bioquimica in April 1988. Also discussed are other visits that were made to universities in Brazil. Three major recommendations to improve the state of biochemistry education in Brazil are presented. (CW)

  19. Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells.

    PubMed Central

    She, H Y; Rockow, S; Tang, J; Nishimura, R; Skolnik, E Y; Chen, M; Margolis, B; Li, W

    1997-01-01

    Src homology domains [i.e., Src homology domain 2 (SH2) and Src homology domain 3 (SH3)] play a critical role in linking receptor tyrosine kinases to downstream signaling networks. A well-defined function of the SH3-SH2-SH3 adapter Grb2 is to link receptor tyrosine kinases, such as the epidermal growth factor receptor (EGFR), to the p21ras-signaling pathway. Grb2 has also been implicated to play a role in growth factor-regulated actin assembly and receptor endocytosis, although the underlying mechanisms remain unclear. In this study, we show that Grb2 interacts through its SH3 domains with the human Wiskott-Aldrich syndrome protein (WASp), which plays a role in regulation of the actin cytoskeleton. We find that WASp is expressed in a variety of cell types and is exclusively cytoplasmic. Although the N-terminal SH3 domain of Grb2 binds significantly stronger than the C-terminal SH3 domain to WASp, full-length Grb2 shows the strongest binding. Both phosphorylation of WASp and its interaction with Grb2, as well as with another adapter protein Nck, remain constitutive in serum-starved or epidermal growth factor-stimulated cells. WASp coimmunoprecipitates with the activated EGFR after epidermal growth factor stimulation. Purified glutathione S-transferase-full-length-Grb2 fusion protein, but not the individual domains of Grb2, enhances the association of WASp with the EGFR, suggesting that Grb2 mediates the association of WASp with EGFR. This study suggests that Grb2 translocates WASp from the cytoplasm to the plasma membrane and the Grb2-WASp complex may play a role in linking receptor tyrosine kinases to the actin cytoskeleton. Images PMID:9307968

  20. CDC’s Second National Report on Biochemical Indicators of Diet and Nutrition in the US Population is a valuable tool for researchers and policy makers123

    PubMed Central

    Pfeiffer, Christine M.; Sternberg, Maya R.; Schleicher, Rosemary L.; Haynes, Bridgette M.H.; Rybak, Michael E.; Pirkle, James L.

    2016-01-01

    The CDC’s National Report on Biochemical Indicators of Diet and Nutrition in the US Population (Nutrition Report) is a serial publication that provides ongoing assessment of the population’s nutritional status. The Nutrition Report presents data on blood and urine biomarker concentrations (selected water- and fat-soluble vitamins and nutrients, trace elements, dietary bioactive compounds) from a representative sample of the population participating in the NHANES. The Second Nutrition Report (released in 2012) contains reference information (means and percentiles) for 58 biomarkers measured during all or part of 2003–2006, stratified by age, sex, and race-ethnicity. Where available, we presented cutpoint-based prevalence data during 2003–2006, and data on changes in biomarker concentrations or prevalence since 1999. Blood vitamin concentrations were generally higher in older (≥60 y) compared to younger (20–39 y) adults and lower in Mexican Americans and non-Hispanic blacks compared to non-Hispanic whites. Nearly 80% of Americans (≥6 y) were not at risk for deficiencies in any of the 7 vitamins studied (A, B-6, B-12, C, D, E and folate). Deficiency rates varied by age, sex, and race-ethnicity. About 90% of women (12–49 y) were not at risk for iron deficiency, but only 68% were not at risk for deficiencies in iron and all 7 vitamins. Young women (20–39 y) had median urine iodine concentrations bordering on insufficiency. First-time data are presented on plasma concentrations of 24 saturated, mono- and polyunsaturated fatty acids. Tabulation and graphical presentation of NHANES data in the Second Nutrition Report benefits those organizations involved in developing and evaluating nutrition policy. PMID:23596164

  1. Physical forcing and physical/biochemical variability of the Mediterranean Sea: a review of unresolved issues and directions for future research

    NASA Astrophysics Data System (ADS)

    Malanotte-Rizzoli, P.; Artale, V.; Borzelli-Eusebi, G. L.; Brenner, S.; Crise, A.; Gacic, M.; Kress, N.; Marullo, S.; Ribera d'Alcalà, M.; Sofianos, S.; Tanhua, T.; Theocharis, A.; Alvarez, M.; Ashkenazy, Y.; Bergamasco, A.; Cardin, V.; Carniel, S.; Civitarese, G.; D'Ortenzio, F.; Font, J.; Garcia-Ladona, E.; Garcia-Lafuente, J. M.; Gogou, A.; Gregoire, M.; Hainbucher, D.; Kontoyannis, H.; Kovacevic, V.; Kraskapoulou, E.; Kroskos, G.; Incarbona, A.; Mazzocchi, M. G.; Orlic, M.; Ozsoy, E.; Pascual, A.; Poulain, P.-M.; Roether, W.; Rubino, A.; Schroeder, K.; Siokou-Frangou, J.; Souvermezoglou, E.; Sprovieri, M.; Tintoré, J.; Triantafyllou, G.

    2014-05-01

    This paper is the outcome of a workshop held in Rome in November 2011 on the occasion of the 25th anniversary of the POEM (Physical Oceanography of the Eastern Mediterranean) program. In the workshop discussions, a number of unresolved issues were identified for the physical and biogeochemical properties of the Mediterranean Sea as a whole, i.e., comprising the Western and Eastern sub-basins. Over the successive two years, the related ideas were discussed among the group of scientists who participated in the workshop and who have contributed to the writing of this paper. Three major topics were identified, each of them being the object of a section divided into a number of different sub-sections, each addressing a specific physical, chemical or biological issue: 1. Assessment of basin-wide physical/biochemical properties, of their variability and interactions. 2. Relative importance of external forcing functions (wind stress, heat/moisture fluxes, forcing through straits) vs. internal variability. 3. Shelf/deep sea interactions and exchanges of physical/biogeochemical properties and how they affect the sub-basin circulation and property distribution. Furthermore, a number of unresolved scientific/methodological issues were also identified and are reported in each sub-section after a short discussion of the present knowledge. They represent the collegial consensus of the scientists contributing to the paper. Naturally, the unresolved issues presented here constitute the choice of the authors and therefore they may not be exhaustive and/or complete. The overall goal is to stimulate a broader interdisciplinary discussion among the scientists of the Mediterranean oceanographic community, leading to enhanced collaborative efforts and exciting future discoveries.

  2. The Biochemical Basis of Minimal Brain Dysfunction

    ERIC Educational Resources Information Center

    Shaywitz, Sally E.; And Others

    1978-01-01

    Available from: C. V. Mosby Company 11830 Westline Industrial Drive St. Louis, Missouri 63141 The research review examines evidence suggesting a biochemical basis for minimal brain dysfunction (MBD), which includes both a relationship between MBD and metabolic abnormalities and a significant genetic influence on the disorder in children. (IM)

  3. Vector Encoding in Biochemical Networks

    NASA Astrophysics Data System (ADS)

    Potter, Garrett; Sun, Bo

    Encoding of environmental cues via biochemical signaling pathways is of vital importance in the transmission of information for cells in a network. The current literature assumes a single cell state is used to encode information, however, recent research suggests the optimal strategy utilizes a vector of cell states sampled at various time points. To elucidate the optimal sampling strategy for vector encoding, we take an information theoretic approach and determine the mutual information of the calcium signaling dynamics obtained from fibroblast cells perturbed with different concentrations of ATP. Specifically, we analyze the sampling strategies under the cases of fixed and non-fixed vector dimension as well as the efficiency of these strategies. Our results show that sampling with greater frequency is optimal in the case of non-fixed vector dimension but that, in general, a lower sampling frequency is best from both a fixed vector dimension and efficiency standpoint. Further, we find the use of a simple modified Ornstein-Uhlenbeck process as a model qualitatively captures many of our experimental results suggesting that sampling in biochemical networks is based on a few basic components.

  4. Biochemical Screening for in utero Drug Exposure.

    PubMed

    Wright, Tricia E

    2015-01-01

    Licit and illicit drug use is a common complication of pregnancy. Accurate information on drug use is difficult to obtain for many reasons as women fear self-disclosure or consenting for drug testing due to stigma, guilt, and fear of social and legal harm. As information about drug use is clinically very important, biochemical testing is an important adjunct to careful maternal history. In addition, research studies depend on accurate measures of exposure when reporting risks of a substance. This paper delineates available matrices for and methods of biochemical drug testing in pregnant women and neonates.

  5. Biochemical Education in Thailand: Past, Present, and Future.

    ERIC Educational Resources Information Center

    Svasti, Jisnuson; Surarit, Rudee

    1991-01-01

    Traces the history of Thailand's biochemical education from its initial evolution from medicine to modern day. Discusses the following aspects of Thailand's modern biochemical education: biochemistry teaching at Thai schools, university departments and biochemistry courses, textbooks, degree programs, interplay between research and teaching, and…

  6. Editorial: ESBES - European Society of Biochemical Engineering Sciences.

    PubMed

    Ferreira, Guilherme; Jungbauer, Alois

    2013-06-01

    The latest ESBES special issue on "Biochemical Engineering Sciences" is edited by Prof. Guilherme Ferreira (Chairman, ESBES) and Prof. Alois Jungbauer (co-Editor-in-Chief, Biotechnology Journal). This special issue comprises the latest research in biochemical engineering science presented at the 9(th) ESBES Conference held in Istanbul, Turkey in 2012.

  7. Biochemical Education in Thailand: Past, Present, and Future.

    ERIC Educational Resources Information Center

    Svasti, Jisnuson; Surarit, Rudee

    1991-01-01

    Traces the history of Thailand's biochemical education from its initial evolution from medicine to modern day. Discusses the following aspects of Thailand's modern biochemical education: biochemistry teaching at Thai schools, university departments and biochemistry courses, textbooks, degree programs, interplay between research and teaching, and…

  8. Use of zinc-finger nucleases to knock out the WAS gene in K562 cells: a human cellular model for Wiskott-Aldrich syndrome

    PubMed Central

    Toscano, Miguel G.; Anderson, Per; Muñoz, Pilar; Lucena, Gema; Cobo, Marién; Benabdellah, Karim; Gregory, Philip D.; Holmes, Michael C.; Martin, Francisco

    2013-01-01

    SUMMARY Mutations in the WAS gene cause Wiskott-Aldrich syndrome (WAS), which is characterized by eczema, immunodeficiency and microthrombocytopenia. Although the role of WASP in lymphocytes and myeloid cells is well characterized, its role on megakaryocyte (MK) development is poorly understood. In order to develop a human cellular model that mimics the megakaryocytic-derived defects observed in WAS patients we used K562 cells, a well-known model for study of megakaryocytic development. We knocked out the WAS gene in K562 cells using a zinc-finger nuclease (ZFN) pair targeting the WAS intron 1 and a homologous donor DNA that disrupted WASP expression. Knockout of WASP on K562 cells (K562WASKO cells) resulted in several megakaryocytic-related defects such as morphological alterations, lower expression of CD41ɑ, lower increments in F-actin polymerization upon stimulation, reduced CD43 expression and increased phosphatidylserine exposure. All these defects have been previously described either in WAS-knockout mice or in WAS patients, validating K562WASKO as a cell model for WAS. However, K562WASPKO cells showed also increased basal F-actin and adhesion, increased expression of CD61 and reduced expression of TGFβ and Factor VIII, defects that have never been described before for WAS-deficient cells. Interestingly, these phenotypic alterations correlate with different roles for WASP in megakaryocytic differentiation. All phenotypic alterations observed in K562WASKO cells were alleviated upon expression of WAS following lentiviral transduction, confirming the role of WASP in these phenotypes. In summary, in this work we have validated a human cellular model, K562WASPKO, that mimics the megakaryocytic-related defects found in WAS-knockout mice and have found evidences for a role of WASP as regulator of megakaryocytic differentiation. We propose the use of K562WASPKO cells as a tool to study the molecular mechanisms involved in the megakaryocytic-related defects observed

  9. Use of zinc-finger nucleases to knock out the WAS gene in K562 cells: a human cellular model for Wiskott-Aldrich syndrome.

    PubMed

    Toscano, Miguel G; Anderson, Per; Muñoz, Pilar; Lucena, Gema; Cobo, Marién; Benabdellah, Karim; Gregory, Philip D; Holmes, Michael C; Martin, Francisco

    2013-03-01

    Mutations in the WAS gene cause Wiskott-Aldrich syndrome (WAS), which is characterized by eczema, immunodeficiency and microthrombocytopenia. Although the role of WASP in lymphocytes and myeloid cells is well characterized, its role on megakaryocyte (MK) development is poorly understood. In order to develop a human cellular model that mimics the megakaryocytic-derived defects observed in WAS patients we used K562 cells, a well-known model for study of megakaryocytic development. We knocked out the WAS gene in K562 cells using a zinc-finger nuclease (ZFN) pair targeting the WAS intron 1 and a homologous donor DNA that disrupted WASP expression. Knockout of WASP on K562 cells (K562WASKO cells) resulted in several megakaryocytic-related defects such as morphological alterations, lower expression of CD41, lower increments in F-actin polymerization upon stimulation, reduced CD43 expression and increased phosphatidylserine exposure. All these defects have been previously described either in WAS-knockout mice or in WAS patients, validating K562WASKO as a cell model for WAS. However, K562WASPKO cells showed also increased basal F-actin and adhesion, increased expression of CD61 and reduced expression of TGFβ and Factor VIII, defects that have never been described before for WAS-deficient cells. Interestingly, these phenotypic alterations correlate with different roles for WASP in megakaryocytic differentiation. All phenotypic alterations observed in K562WASKO cells were alleviated upon expression of WAS following lentiviral transduction, confirming the role of WASP in these phenotypes. In summary, in this work we have validated a human cellular model, K562WASPKO, that mimics the megakaryocytic-related defects found in WAS-knockout mice and have found evidences for a role of WASP as regulator of megakaryocytic differentiation. We propose the use of K562WASPKO cells as a tool to study the molecular mechanisms involved in the megakaryocytic-related defects observed in WAS

  10. A Biochemical Double Slit

    NASA Astrophysics Data System (ADS)

    Kominis, Iannis

    2011-03-01

    Radical-ion-pair reactions, fundamental in photosynthesis and at the basis of the avian magnetic compass mechanism, have been recently shown to offer a rich playground for applying methods and concepts from quantum measurement/quantum information science. We will demonstrate that radical-ion-pair reactions are almost the exact analog of the optical double slit experiment, i.e. Nature has already engineered biochemical reactions performing the act of quantum interference. We will further elaborate on the non-trivial quantum effects pertaining in these reactions and the recent debate on their fundamental theoretical description that these effects have sparked.

  11. A comparison of lifestyle, genetic, bioclinical and biochemical variables of offspring with and without family histories of premature coronary heart disease: the experience of the European Atherosclerosis Research Studies.

    PubMed

    De Backer, G; De Henauw, S; Sans, S; Nicaud, V; Masana, L; Visvikis, S; Gerdes, C; Wilhelmsen, L

    1999-06-01

    Lifestyle, genetic, bioclinical and biochemical factors of European university students aged 18-26 years, with and without documented paternal histories of premature coronary heart disease, have been compared in the European Atherosclerosis Research Studies (EARS) I and II. To highlight consistencies and inconsistencies between findings in the two studies. All measurements were made according to strict protocols, by trained technicians using validated methods. The results for men in EARS I are compared with those from EARS II which was confined to men. In both studies we found no differences between cases and controls in lifestyle factors and bioclinical factors except that controls were taller. We found inconsistent differences between obesity indices and antecedents of arterial hypertension. In both studies we found consistent differences between cases and controls in levels of total cholesterol and apolipoprotein B, both levels being higher in cases. The lack of any difference between levels of high-density lipoprotein cholesterol and apolipoprotein A1 was also found consistently. Inconsistent differences were found for levels of triglycerides and apolipoprotein E. For most of the candidate genes that were studied, no differences between cases and controls were found, but different polymorphisms were associated with levels of lipids, apoproteins and fibrinogen independently of case-control status. Some of these associations were potentiated by lifestyle factors. The interaction between genetic and environmental factors is further illustrated with results from the association of apolipoprotein E polymorphism with the level of apolipoprotein B and a variety of other determinants of apolipoprotein B level. In the EARS studies a documented family history of premature coronary heart disease was mainly expressed in terms of biochemical factors that are determined both by nature and by nurture.

  12. Wiskott-Aldrich Syndrome Interacting Protein Deficiency Uncovers the Role of the Co-receptor CD19 as a Generic Hub for PI3 Kinase Signaling in B Cells.

    PubMed

    Keppler, Selina Jessica; Gasparrini, Francesca; Burbage, Marianne; Aggarwal, Shweta; Frederico, Bruno; Geha, Raif S; Way, Michael; Bruckbauer, Andreas; Batista, Facundo D

    2015-10-20

    Humans with Wiskott-Aldrich syndrome display a progressive immunological disorder associated with compromised Wiskott-Aldrich Syndrome Interacting Protein (WIP) function. Mice deficient in WIP recapitulate such an immunodeficiency that has been attributed to T cell dysfunction; however, any contribution of B cells is as yet undefined. Here we have shown that WIP deficiency resulted in defects in B cell homing, chemotaxis, survival, and differentiation, ultimately leading to diminished germinal center formation and antibody production. Furthermore, in the absence of WIP, several receptors, namely the BCR, BAFFR, CXCR4, CXCR5, CD40, and TLR4, were impaired in promoting CD19 co-receptor activation and subsequent PI3 kinase (PI3K) signaling. The underlying mechanism was due to a distortion in the actin and tetraspanin networks that lead to altered CD19 cell surface dynamics. In conclusion, our findings suggest that, by regulating the cortical actin cytoskeleton, WIP influences the function of CD19 as a general hub for PI3K signaling. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Biochemical Reversal of Aging

    NASA Astrophysics Data System (ADS)

    Ely, John T. A.

    2006-03-01

    We cite our progress on biochemical reversal of aging. However, it may be circa 2 years before we have necessary substances at low cost. Meanwhile, without them, a number of measures can be adopted providing marked improvement for the problems of aging in modern societies. For example, enzymes are needed to excrete toxins that accelerate aging; Hg is the ultimate toxin that disables all enzymes (including those needed to excrete Hg itself). Low Hg level in the urine, due to loss of excretory ability, causes the diagnosis of Hg toxicity to almost always be missed. Hg sources must be removed from the body! Another example is excess sugar; hyperglycemia decreases intracellular ascorbic acid (AA) by competitively inhibiting the insulin- mediated active transport of AA into cells. Thus, immunity is impaired by low leucocyte AA. AA is needed for new proteins in aging tissues. Humans must supplement AA; their need same as in AA-synthesizing mammals.

  14. Misleading biochemical laboratory test results

    PubMed Central

    Nanji, Amin A.

    1984-01-01

    This article reviews the general and specific factors that interfere with the performance of common biochemical laboratory tests and the interpretation of their results. The clinical status of the patient, drug interactions, and in-vivo and in-vitro biochemical interactions and changes may alter the results obtained from biochemical analysis of blood constituents. Failure to recognize invalid laboratory test results may lead to injudicious and dangerous management of patients. PMID:6375845

  15. Physical forcing and physical/biochemical variability of the Mediterranean Sea: a review of unresolved issues and directions for future research

    NASA Astrophysics Data System (ADS)

    Malanotte-Rizzoli, P.; Artale, V.; Borzelli-Eusebi, G. L.; Brenner, S.; Civitarese, G.; Crise, A.; Font, J.; Gacic, M.; Kress, N.; Marullo, S.; Ozsoy, E.; Ribera d'Alcalà, M.; Roether, W.; Schroeder, K.; Sofianos, S.; Tanhua, T.; Theocharis, A.; Alvarez, M.; Ashkenazy, Y.; Bergamasco, A.; Cardin, V.; Carniel, S.; D'Ortenzio, F.; Garcia-Ladona, E.; Garcia-Lafuente, J. M.; Gogou, A.; Gregoire, M.; Hainbucher, D.; Kontoyannis, H.; Kovacevic, V.; Krasakapoulou, E.; Krokos, G.; Incarbona, A.; Mazzocchi, M. G.; Orlic, M.; Pascual, A.; Poulain, P.-M.; Rubino, A.; Siokou-Frangou, J.; Souvermezoglou, E.; Sprovieri, M.; Taupier-Letage, I.; Tintoré, J.; Triantafyllou, G.

    2013-07-01

    convection cells are much more amenable to direct observational surveys and mooring arrays. An ubiquitous, energetic mesoscale and sub-mesoscale eddy field is superimposed to and interacts with the sub-basin scale, wind-driven gyres that characterize the upper thermocline circulation. Three different scales of motion are therefore superimposed producing a richness of interaction processes which typify similar interactions in unexplored ocean regions. Both wide and narrow shelves are present separated by steep continental slopes from the deep interiors. Cross-shelf fluxes of physical as well biogeochemical parameters are crucial in determining the properties of the shallow versus deep local ecosystems and their trophic chain. Most importantly, the Mediterranean Sea is a basin of contrasting ecosystems, from the strongly oligotrophic deep interiors to the fully eutrophic northern Adriatic characterized by recurrent, anomalous algal blooms and related anoxia events. This review focuses on the identification of the major unresolved scientific issues and wants also to provide directions for future research which may lead to the formulation of interdisciplinary, collaborative implementation plans to address these issues both theoretically and observationally.

  16. A randomized controlled trial investigating the effect of Pycnogenol and Bacopa CDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: the Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910)

    PubMed Central

    2012-01-01

    Background One of the major challenges associated with our ageing population is the increasing incidence of age-associated cognitive decline, which has significant implications for an individual's ability to lead a productive and fulfilling life. In pure economic terms the costs of ageing reflects decreased productivity and engagement with the workforce. The maintenance of brain health underpinning intact cognition is a key factor to maintaining a positive, engaged, and productive lifestyle. In light of this, the role of diet, including supplementation with nutritional and even pharmacological interventions capable of ameliorating the neurocognitive changes that occur with age constitute vital areas of research. Methods In order to reduce cognitive ageing, the ARC longevity intervention (ARCLI) was developed to examine the effects of two promising natural pharmacologically active supplements on cognitive performance. ARCLI is a randomized, placebo-controlled, double-blind, 3-arm clinical trial in which 465 participants will be randomized to receive an extract of Bacopa monnieri (CDRI08 300 mg/day), Pycnogenol (150 mg/day), or placebo daily for 12 months. Participants will be tested at baseline and then at 3, 6 and 12 months post-randomization on a wide battery of cognitive, neuropsychological and mood measures, cardiovascular (brachial and aortic systolic and diastolic blood pressures as well as arterial stiffness), biochemical (assays to measure inflammation, oxidative stress and safety) as well as genetic assessments (telomere length and several Single Nucleotide Polymorphisms). The primary aim is to investigate the effects of these supplements on cognitive performance. The secondary aims are to explore the time-course of cognitive enhancement as well as potential cardiovascular and biochemical mechanisms underpinning cognitive enhancement over the 12 months of administration. ARCLI will represent one of the largest and most comprehensive experimental clinical

  17. Early Salvage Hormonal Therapy for Biochemical Failure Improved Survival in Prostate Cancer Patients After Neoadjuvant Hormonal Therapy Plus Radiation Therapy-A Secondary Analysis of Irish Clinical Oncology Research Group 97-01

    SciTech Connect

    Mydin, Aminudin R.; Dunne, Mary T.; Finn, Marie A.; Armstrong, John G.

    2013-01-01

    Purpose: To assess the survival benefit of early vs late salvage hormonal therapy (HT), we performed a secondary analysis on patients who developed recurrence from Irish Clinical Oncology Research Group 97-01, a randomized trial comparing 4 vs 8 months neoadjuvant HT plus radiation therapy (RT) in intermediate- and high-risk prostate adenocarcinoma. Methods and Materials: A total of 102 patients from the trial who recurred were analyzed at a median follow-up of 8.5 years. The patients were divided into 3 groups based on the timing of salvage HT: 57 patients had prostate-specific antigen (PSA) {<=}10 ng/mL and absent distant metastases (group 1, early), 21 patients had PSA >10 ng/mL and absent distant metastases (group 2, late), and 24 patients had distant metastases (group 3, late). The endpoint analyzed was overall survival (OS) calculated from 2 different time points: date of enrolment in the trial (OS1) and date of initiation of salvage HT (OS2). Survival was estimated using Kaplan-Meier curves and a Cox regression model. Results: The OS1 differed significantly between groups (P<.0005): OS1 at 10 years was 78% in group 1, 42% in group 2, and 29% in group 3. The OS2 also differed significantly between groups (P<.0005): OS2 at 6 years was 70% in group 1, 47% in group 2, and 22% in group 3. Group 1 had the longest median time from end of RT to biochemical failure compared with groups 2 and 3 (3.3, 0.9, and 1.7 years, respectively; P<.0005). Group 1 also had the longest median PSA doubling time compared with groups 2 and 3 (9.9, 3.6, and 2.4 months, respectively; P<.0005). On multivariate analysis, timing of salvage HT, time from end of RT to biochemical failure, and PSA nadir on salvage HT were significant predictors of survival. Conclusion: Early salvage HT based on PSA {<=}10 ng/mL and absent distant metastases improved survival in patients with prostate cancer after failure of initial treatment with neoadjuvant HT plus RT.

  18. Rapamycin regulates biochemical metabolites

    PubMed Central

    Tucci, Paola; Porta, Giovanni; Agostini, Massimiliano; Antonov, Alexey; Garabadgiu, Alexander Vasilievich; Melino, Gerry; Willis, Anne E

    2013-01-01

    The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth, and deregulation of this pathway is associated with tumorigenesis. p53, and its less investigated family member p73, have been shown to interact closely with mTOR pathways through the transcriptional regulation of different target genes. To investigate the metabolic changes that occur upon inhibition of the mTOR pathway and the role of p73 in this response primary mouse embryonic fibroblast from control and TAp73−/− were treated with the macrocyclic lactone rapamycin. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analysis were used to obtain a rapamycin-dependent global metabolome profile from control or TAp73−/− cells. In total 289 metabolites involved in selective pathways were identified; 39 biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stress response. PMID:23839040

  19. Optical chemical and biochemical sensors: new trends (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Baldini, F.; Giannetti, A.

    2005-06-01

    Chemical and biochemical sensing is under the extensive research all over the world and many chemical and biochemical sensors are finding increasing number of applications in industry, environmental monitoring, medicine, biomedicine and chemical analysis. This is evidenced by each-year-growing number of international scientific conferences, in which advances in the field of the sensors are reported. One of the main reason why only a few sensors reach the international market, notwithstanding the high number of laboratory prototype described in many peer reviewed papers, lies in the fact that a biochemical sensor is a highly interdisciplinary "object" the realization of which requires the team work of scientists coming from different areas such as chemistry, physics, optoelectronics, engineering, biochemistry, and medicine. And this peculiarity is not easily found in the research teams. In the present paper, the fundamental bases of chemical and biochemical optical sensing are summarised and the new trends are described.

  20. A Course in... Biochemical Engineering.

    ERIC Educational Resources Information Center

    Ng, Terry K-L.; And Others

    1988-01-01

    Describes a chemical engineering course for senior undergraduates and first year graduate students in biochemical engineering. Discusses five experiments used in the course: aseptic techniques, dissolved oxygen measurement, oxygen uptake by yeast, continuous sterilization, and cultivation of microorganisms. (MVL)

  1. A Course in... Biochemical Engineering.

    ERIC Educational Resources Information Center

    Ng, Terry K-L.; And Others

    1988-01-01

    Describes a chemical engineering course for senior undergraduates and first year graduate students in biochemical engineering. Discusses five experiments used in the course: aseptic techniques, dissolved oxygen measurement, oxygen uptake by yeast, continuous sterilization, and cultivation of microorganisms. (MVL)

  2. Explorations into Chemical Reactions and Biochemical Pathways.

    PubMed

    Gasteiger, Johann

    2016-12-01

    A brief overview of the work in the research group of the present author on extracting knowledge from chemical reaction data is presented. Methods have been developed to calculate physicochemical effects at the reaction site. It is shown that these physicochemical effects can quite favourably be used to derive equations for the calculation of data on gas phase reactions and on reactions in solution such as aqueous acidity of alcohols or carboxylic acids or the hydrolysis of amides. Furthermore, it is shown that these physicochemical effects are quite effective for assigning reactions into reaction classes that correspond to chemical knowledge. Biochemical reactions constitute a particularly interesting and challenging task for increasing our understanding of living species. The BioPath.Database is a rich source of information on biochemical reactions and has been used for a variety of applications of chemical, biological, or medicinal interests. Thus, it was shown that biochemical reactions can be assigned by the physicochemical effects into classes that correspond to the classification of enzymes by the EC numbers. Furthermore, 3D models of reaction intermediates can be used for searching for novel enzyme inhibitors. It was shown in a combined application of chemoinformatics and bioinformatics that essential pathways of diseases can be uncovered. Furthermore, a study showed that bacterial flavor-forming pathways can be discovered.

  3. Inkjet printed (bio)chemical sensing devices.

    PubMed

    Komuro, Nobutoshi; Takaki, Shunsuke; Suzuki, Koji; Citterio, Daniel

    2013-07-01

    Inkjet printing has evolved from an office printing application to become an important tool in industrial mass fabrication. In parallel, this technology is increasingly used in research laboratories around the world for the fabrication of entire (bio)chemical sensing devices or single functional elements of such devices. Regularly stated characteristics of inkjet printing making it attractive to replace an alternative material deposition method are low cost, simplicity, high resolution, speed, reproducibility, flexibility, non-contact, and low amount of waste generated. With this review, we give an overview over areas of (bio)chemical sensing device development profiting from inkjet printing applications. A variety of printable functional sensor elements are introduced by examples, and the advantages and challenges of the inkjet method are pointed out. It is demonstrated that inkjet printing is already a routine tool for the fabrication of some (bio)chemical sensing devices, but also that novel applications are being continuously developed. Finally, some inherent limitations of the method and challenges for the further exploitation of this technology are pointed out.

  4. Cytokines as biochemical markers for knee osteoarthritis

    PubMed Central

    Mabey, Thomas; Honsawek, Sittisak

    2015-01-01

    Osteoarthritis (OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show biochemical changes within joint tissue which can occur many years before symptoms become apparent. The need for better diagnostic and prognostic tools is heightened with the prevalence of OA set to increase in aging and obese populations. As inflammation is increasingly being considered an important part of OAs pathophysiology, cytokines are being assessed as possible candidates for biochemical markers. Cytokines, both pro- and anti-inflammatory, as well as angiogenic and chemotactic, have in recent years been studied for relevant characteristics. Biochemical markers show promise in determination of the severity of disease in addition to monitoring of the efficacy and safety of disease-modifying OA drugs, with the potential to act as diagnostic and prognostic tools. Currently, the diagnostic power of interleukin (IL)-6 and the relationship to disease burden of IL-1β, IL-15, tumor necrosis factor-α, and vascular endothelial growth factor make these the best candidates for assessment. Grouping appropriate cytokine markers together and assessing them collectively alongside other bone and cartilage degradation products will yield a more statistically powerful tool in research and clinical applications, and additionally aid in distinguishing between OA and a number of other diseases in which cytokines are known to have an involvement. Further large scale studies are needed to assess the validity and efficacy of current biomarkers, and to discover other potential biomarker candidates. PMID:25621214

  5. [Basic biochemical processes in glaucoma progression].

    PubMed

    von Thun und Hohenstein-Blaul, N; Kunst, S; Pfeiffer, N; Grus, F H

    2015-05-01

    The term glaucoma summarizes a group of eye diseases that are accompanied by impairments of the optic nerve and related visual field deficits. An early diagnosis of glaucoma is currently not possible due to a lack of diagnostic tests; therefore, in most cases the disease is diagnosed many years after onset, which prevents an early therapy. The known risk factors for the development and progression of glaucomatous optic neuropathy comprise elevated intraocular pressure and a broad range of pressure fluctuations as well as lipometabolic disorders, genetic factor and diabetes. The consequences include the induction of anti-inflammatory proteins, elevated levels of oxidative stress and the destruction of retinal ganglion cells. Changes in the autoantibody repertoire have also been observed in the course of the disease. Basic ophthalmological research therefore focuses on the investigation of basic biochemical processes in the course of the disease. A better understanding of physiological and biochemical events is sought in order to develop new and more sensitive diagnostic options and to allow more targeted therapeutic measures. The understanding of biochemical processes allows a better insight into glaucoma progression to be gained, which will lead to improvements in diagnosis and therapy.

  6. Approaches to Chemical and Biochemical Information and Signal Processing

    NASA Astrophysics Data System (ADS)

    Privman, Vladimir

    2012-02-01

    We outline models and approaches for error control required to prevent buildup of noise when ``gates'' and other ``network elements'' based on (bio)chemical reaction processes are utilized to realize stable, scalable networks for information and signal processing. We also survey challenges and possible future research. [4pt] [1] Control of Noise in Chemical and Biochemical Information Processing, V. Privman, Israel J. Chem. 51, 118-131 (2010).[0pt] [2] Biochemical Filter with Sigmoidal Response: Increasing the Complexity of Biomolecular Logic, V. Privman, J. Halamek, M. A. Arugula, D. Melnikov, V. Bocharova and E. Katz, J. Phys. Chem. B 114, 14103-14109 (2010).[0pt] [3] Towards Biosensing Strategies Based on Biochemical Logic Systems, E. Katz, V. Privman and J. Wang, in: Proc. Conf. ICQNM 2010 (IEEE Comp. Soc. Conf. Publ. Serv., Los Alamitos, California, 2010), pages 1-9.

  7. BEST: Biochemical Engineering Simulation Technology

    SciTech Connect

    Not Available

    1996-01-01

    The idea of developing a process simulator that can describe biochemical engineering (a relatively new technology area) was formulated at the National Renewable Energy Laboratory (NREL) during the late 1980s. The initial plan was to build a consortium of industrial and U.S. Department of Energy (DOE) partners to enhance a commercial simulator with biochemical unit operations. DOE supported this effort; however, before the consortium was established, the process simulator industry changed considerably. Work on the first phase of implementing various fermentation reactors into the chemical process simulator, ASPEN/SP-BEST, is complete. This report will focus on those developments. Simulation Sciences, Inc. (SimSci) no longer supports ASPEN/SP, and Aspen Technology, Inc. (AspenTech) has developed an add-on to its ASPEN PLUS (also called BioProcess Simulator [BPS]). This report will also explain the similarities and differences between BEST and BPS. ASPEN, developed by the Massachusetts Institute of Technology for DOE in the late 1970s, is still the state-of-the-art chemical process simulator. It was selected as the only simulator with the potential to be easily expanded into the biochemical area. ASPEN/SP, commercially sold by SimSci, was selected for the BEST work. SimSci completed work on batch, fed-batch, and continuous fermentation reactors in 1993, just as it announced it would no longer commercially support the complete ASPEN/SP product. BEST was left without a basic support program. Luckily, during this same time frame, AspenTech was developing a biochemical simulator with its version of ASPEN (ASPEN PLUS), which incorporates most BEST concepts. The future of BEST will involve developing physical property data and models appropriate to biochemical systems that are necessary for good biochemical process design.

  8. Biotechnology for a renewable resources chemicals and fuels industry, biochemical engineering R and D

    SciTech Connect

    Villet, R.H.

    1980-04-01

    To establish an effective biotechnology of biomass processing for the production of fuels and chemicals, an integration of research in biochemical engineering, microbial genetics, and biochemistry is required. Reduction of the costs of producing chemicals and fuels from renewable resources will hinge on extensive research in biochemical engineering.

  9. Overview of the DOE/SERI Biochemical Conversion Program

    SciTech Connect

    Wright, J D

    1986-09-01

    The Solar Energy Research Institute manages a program of research and development on the biochemical conversion of renewable lignocellulosic materials to liquid fuels for the Department of Energy's Biofuels and Municipal Waste Technology Division. The Biochemical Conversion Program is mission oriented so effort is concentrated on technologies which appear to have the greatest potential for being adopted by the private sector to economically convert lignocellulosic materials into high value liquid transportation fuels such as ethanol. The program is structured to supply the technology for such fuels to compete economically first as an octane booster or fuel additive, and, with additional improvements, as a neat fuel. 18 refs., 3 figs., 1 tab.

  10. Biochemical Control of Marine Fouling

    DTIC Science & Technology

    1988-01-14

    amino acid and catecholamine analyses by ion-exchange chromatography, and determination with ninhydrin , performed in collaboration with Dr. Herbert...attempted to design and test new, potentially specific (nonhazardous, environmentally safe) biochemical inhibitors of the recruitment and fouling...reaction- sequences. In this effort, we have concentrated first on the design and testing of agents which specifically block the larval receptors and

  11. FY 1987 biochemical conversion/alcohol fuels program: Annual report

    SciTech Connect

    Not Available

    1988-11-01

    Ethanol, a high-octane liquid fuel compatible with today's transportation system, can be produced by biological processes from lignocellulosic feedstocks. The Biochemical Conversion/Alcohol Fuels Research Program managed by the Solar Energy Research Institute (SERI) for the US Department of Energy's Biofuels and Municipal Waste Technology Division carries out a program of research and development with the goals of developing processes for converting lignocellulosic materials to ethanol and other fuels in an efficient and cost-effective manner, and facilitating the adoption of these processes by industry. This annual report for FY 1987 summarizes the state of the art and the research conducted by the Biochemical Conversion/Alcohol Fuels Research Program in the past year. The appendices contain detailed descriptions of the individual research projects, organized into the following categories: Acid Hydrolysis, Enzymatic Hydrolysis, Xylose Fermentation, and Lignin Conversion.

  12. Bone marrow transplantation in a child with Wiskott-Aldrich syndrome latently infected with acyclovir-resistant (ACV(r)) herpes simplex virus type 1: emergence of foscarnet-resistant virus originating from the ACV(r) virus.

    PubMed

    Saijo, Masayuki; Yasuda, Yukiharu; Yabe, Hiromasa; Kato, Shunichi; Suzutani, Tatsuo; De Clercq, Erik; Niikura, Masahiro; Maeda, Akihiko; Kurane, Ichiro; Morikawa, Shigeru

    2002-09-01

    A human leukocyte antigen (HLA)-matched unrelated bone marrow transplantation (BMT) was performed in a 13-year-old patient with the congenital immunodeficiency syndrome, Wiskott-Aldrich syndrome. The patient had a history of acyclovir (ACV)-resistant (ACV(r)) herpes simplex virus type 1 (HSV-1) infections prior to BMT. After BMT, the skin lesions caused by HSV-1 relapsed on the face and genito-anal areas. Ganciclovir (GCV) therapy was initiated, but the mucocutaneous lesions worsened. An HSV-1 isolate recovered from the lesions during this episode was resistant to both ACV and GCV. The ACV(r) isolate was confirmed to have the same mutation in the viral thymidine kinase (TK) gene as that of the previously isolated ACV(r) isolates from the patient. After treatment switch to foscarnet (PFA), there was a satisfactory remission but not a complete recovery. Although the mucocutaneous lesions improved, a PFA-resistant (PFA(r)) HSV-1 was isolated 1 month after the start of PFA therapy. The PFA(r) HSV-1 isolate coded for the same mutation in the viral TK gene as the ACV(r) HSV-1 isolates. Furthermore, the PFA(r) isolate also expressed a mutated viral DNA polymerase (DNA pol) with an amino acid (Gly) substitution for Val at position 715. This is the first report on the clinical course of a BMT-associated ACV(r) HSV-1 infection that subsequently developed resistance to foscarnet as well.

  13. Interferometric biochemical and chemical sensors

    NASA Astrophysics Data System (ADS)

    Gauglitz, Guenter; Brecht, Andreas; Kraus, Gerolf

    1995-09-01

    Interferometric principles have gained wide acceptance in the field of chemical and biochemical sensing. Reflectometric interference spectrometry sensors using white light multiple reflections at thin layers, structures of polymers, or monolayers of biochemicals are discussed in a survey. These are compared to other techniques, especially methods using surface plasmon resonance and grating couplers. Applications in the area of environmental monitoring in public safety are given, demonstrating the results for halogenated hydrocarbons in air and water as well as pesticides in ground water. Calibration curves, limits of decision, of detection, and of determination are specified and discussed with respect to EU limits. The application of multivariate data analysis is considered including artificial neuronal networks for multisensor systems and referencing in the case of gas sensors.

  14. Biochemical Disincentives to Fertilizing Cellulosic Ethanol Crops

    NASA Astrophysics Data System (ADS)

    Gallagher, M. E.; Hockaday, W. C.; Snapp, S.; McSwiney, C.; Baldock, J.

    2010-12-01

    Corn grain biofuel crops produce the highest yields when the cropping ecosystem is not nitrogen (N)-limited, achieved by application of fertilizer. There are environmental consequences for excessive fertilizer application to crops, including greenhouse gas emissions, hypoxic “dead zones,” and health problems from N runoff into groundwater. The increase in corn acreage in response to demand for alternative fuels (i.e. ethanol) could exacerbate these problems, and divert food supplies to fuel production. A potential substitute for grain ethanol that could reduce some of these impacts is cellulosic ethanol. Cellulosic ethanol feedstocks include grasses (switchgrass), hardwoods, and crop residues (e.g. corn stover, wheat straw). It has been assumed that these feedstocks will require similar N fertilization rates to grain biofuel crops to maximize yields, but carbohydrate yield versus N application has not previously been monitored. We report the biochemical stocks (carbohydrate, protein, and lignin in Mg ha-1) of a corn ecosystem grown under varying N levels. We measured biochemical yield in Mg ha-1 within the grain, leaf and stem, and reproductive parts of corn plants grown at seven N fertilization rates (0-202 kg N ha-1), to evaluate the quantity and quality of these feedstocks across a N fertilization gradient. The N fertilization rate study was performed at the Kellogg Biological Station-Long Term Ecological Research Site (KBS-LTER) in Michigan. Biochemical stocks were measured using 13C nuclear magnetic resonance spectroscopy (NMR), combined with a molecular mixing model (Baldock et al. 2004). Carbohydrate and lignin are the main biochemicals of interest in ethanol production since carbohydrate is the ethanol feedstock, and lignin hinders the carbohydrate to ethanol conversion process. We show that corn residue carbohydrate yields respond only weakly to N fertilization compared to grain. Grain carbohydrate yields plateau in response to fertilization at

  15. Dialogues as Teaching Tools in the Biochemical Sciences.

    ERIC Educational Resources Information Center

    Roberts-Kirchhoff, Elizabeth S.; Caspers, Mary Lou

    2001-01-01

    Reports on the implementation of a group project whose goal was to write a dialogue that explores one area in which advances in biochemical research give rise to ethical and societal considerations. Reports that the project was regarded highly by students. (Author/MM)

  16. Biochemical Markers of Brain Injury: Applications to Combat Casualty Care

    DTIC Science & Technology

    2004-09-01

    these failures [6]. Unlike other organ-based diseases where rapid diagnosis employing biomarkers (usually involving blood tests) prove invaluable...implementation of appropriate triage and medical management. Criteria For Biochemical/Surrogate Markers: In the course of research on biomarkers ...our laboratories have developed criteria for biomarker development. As reflected in the present proposal, useful biomarkers should employ readily

  17. Biochemical adaptation to ocean acidification.

    PubMed

    Stillman, Jonathon H; Paganini, Adam W

    2015-06-01

    The change in oceanic carbonate chemistry due to increased atmospheric PCO2  has caused pH to decline in marine surface waters, a phenomenon known as ocean acidification (OA). The effects of OA on organisms have been shown to be widespread among diverse taxa from a wide range of habitats. The majority of studies of organismal response to OA are in short-term exposures to future levels of PCO2 . From such studies, much information has been gathered on plastic responses organisms may make in the future that are beneficial or harmful to fitness. Relatively few studies have examined whether organisms can adapt to negative-fitness consequences of plastic responses to OA. We outline major approaches that have been used to study the adaptive potential for organisms to OA, which include comparative studies and experimental evolution. Organisms that inhabit a range of pH environments (e.g. pH gradients at volcanic CO2 seeps or in upwelling zones) have great potential for studies that identify adaptive shifts that have occurred through evolution. Comparative studies have advanced our understanding of adaptation to OA by linking whole-organism responses with cellular mechanisms. Such optimization of function provides a link between genetic variation and adaptive evolution in tuning optimal function of rate-limiting cellular processes in different pH conditions. For example, in experimental evolution studies of organisms with short generation times (e.g. phytoplankton), hundreds of generations of growth under future conditions has resulted in fixed differences in gene expression related to acid-base regulation. However, biochemical mechanisms for adaptive responses to OA have yet to be fully characterized, and are likely to be more complex than simply changes in gene expression or protein modification. Finally, we present a hypothesis regarding an unexplored area for biochemical adaptation to ocean acidification. In this hypothesis, proteins and membranes exposed to the

  18. Pheochromocytoma-paraganglioma: Biochemical and genetic diagnosis.

    PubMed

    Cano Megías, Marta; Rodriguez Puyol, Diego; Fernández Rodríguez, Loreto; Sención Martinez, Gloria Lisette; Martínez Miguel, Patricia

    Pheochromocytomas and paragangliomas are tumours derived from neural crest cells, which can be diagnosed by biochemical measurement of metanephrine and methoxytyramine. Advances in genetic research have identified many genes involved in the pathogenesis of these tumours, suggesting that up to 35-45% may have an underlying germline mutation. These genes have a singular transcriptional signature and can be grouped into 2 clusters (or groups): cluster 1 (VHL and SHDx), involved in angiogenesis and hypoxia pathways; and cluster 2 (MEN2 and NF1), linked to the kinase signalling pathway. In turn, these genes are associated with a characteristic biochemical phenotype (noradrenergic and adrenergic), and clinical features (location, biological behaviour, age of presentation, etc.) in a large number of cases. Early diagnosis of these tumours, accompanied by a correct genetic diagnosis, should eventually become a priority to enable better treatment, early detection of complications, proper screening of family members and related tumours, as well as an improvement in the overall prognosis of these patients. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  19. Biochemical enzyme analysis in acute leukaemia.

    PubMed Central

    Drexler, H G; Gaedicke, G; Minowada, J

    1985-01-01

    This report summarises the current knowledge regarding the clinical utility of biochemical enzyme markers for both diagnostic and therapeutic purposes in acute leukaemia. The enzymes studied most extensively in this field are terminal deoxynucleotidyl transferase, adenosine deaminase, 5'-nucleotidase, purine nucleoside phosphorylase, and acid phosphatase, esterase, hexosaminidase isoenzymes. For each enzyme, the quantitative and qualitative characteristics in various immunologically defined subclasses of acute leukaemia are described. The quantitative evaluation of enzyme activities represents an adjunctive classification technique which should be incorporated into the multivariate analysis, the "multiple marker analysis." By qualitative characterisation pronounced heterogeneity of leukaemia subsets is uncovered. The application of 2'-deoxycoformycin, a specific inhibitor of adenosine deaminase, and the potential usefulness of two other enzymes as targets for treatment with selective agents is discussed. The concept that gene products expressed at certain developmental stages of normal cells can similarly be detected in leukaemic cells (which therefore seem to be "frozen" or "arrested" at this particular maturation/differentiation stage) is supported by the results obtained in enzyme studies. Besides their practical clinical importance for classification and treatment of acute leukaemias, biochemical enzyme markers constitute a valuable research tool to disclose biological properties of leukaemic cells. PMID:2981904

  20. Biochemical responses of the Skylab crewman

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Rambaut, P. C.

    1974-01-01

    The biochemical investigations of the Skylab crewmen were designed to study the physiological changes that were observed on flight crews returning from previous space flight missions as well as to study those changes expected to result from prolonged weightless exposure. These studies can be divided into two broad categories. One category included routine blood studies similar to those used in clinical medical practice. The second included research-type endocrine analyses used to investigate more thoroughly the metabolic/endocrine responses to the space flight environment. The premission control values indicated that all Skylab crewmen were healthy and were free from biochemical abnormalities. The routine results during and after flight showed slight but significant changes in electrolytes, glucose, total protein, osmolality, uric acid, cholesterol, and creatinine. Plasma hormal changes included adrenocorticotrophic hormone, cortisol, angiotensin I, aldosterone, insulin, and thyroxine. The 24-hour urine analyses results revealed increased excretion of cortisol, catecholamines, antidiuretic hormone, and aldosterone as well as excretion of significant electrolyte and uric acid during the Skylab flights.

  1. Biochemical testing of thyroid function.

    PubMed

    Klee, G G; Hay, I D

    1997-12-01

    Various published guidelines recommending serum thyrotropin (TSH)-first thyroid testing are outlined. The entities called "subclinical hypothyroidism" and "subclinical hyperthyroidism" are defined on the basis of abnormal TSH concentrations and normal values of other biochemical thyroid tests. The controversies about follow-up and treatment of these disorders are discussed. The laboratory experience of Mayo Clinic Rochester in using TSH-first thyroid testing and the subsequent implementation of a thyroid test ordering cascade are presented. Finally, recommendations are given for further optimizing laboratory testing for thyroid disorders.

  2. Biochemical structure of Calendula officinalis.

    PubMed

    Korakhashvili, A; Kacharava, T; Kiknavelidze, N

    2007-01-01

    Calendula officinalis is a well known medicinal herb. It is common knowledge that its medicinal properties are conditioned on biologically active complex substances of Carotin (Provitamin A), Stearin, Triterpiniod, Plavonoid, Kumarin, macro and micro compound elements. Because of constant need in raw material of Calendula officinalis, features of its ontogenetic development agro-biological qualities in various eco regions of Georgia were investigated. The data of biologically active compounds, biochemical structure and the maintenance both in flowers and in others parts of plant is presented; the pharmacological activity and importance in medicine was reviewed.

  3. Hyponatraemia: biochemical and clinical perspectives.

    PubMed

    Gill, G; Leese, G

    1998-09-01

    Hyponatraemia is a common bio-chemical abnormality, occurring in about 15% of hospital inpatients. It is often associated with severe illness and relatively poor outcome. Pathophysiologically, hyponatraemia may be spurious, dilutional, depletional or redistributional. Particularly difficult causes and concepts of hyponatraemia are the syndrome of inappropriate antidiuresis and the sick cell syndrome, which are discussed here in detail. Therapy should always be targeted at the underlying disease process. 'Hyponatraemic symptoms' are of doubtful importance, and may be more related to water overload and/or the causative disease, than to hyponatraemia per se. Artificial elevation of plasma sodium by saline infusion carries the risk of induction of osmotic demyelination (central pontine myelinolysis).

  4. Optofluidics in bio-chemical analysis

    NASA Astrophysics Data System (ADS)

    Guo, Yunbo; Fan, Xudong

    2012-01-01

    Optofluidics organically integrates microfluidics and photonics and is an emerging technology in biological and chemical analysis. In this paper, we overview the recent studies in bio-chemical sensing applications of optofluidics. Particularly, we report the research progress in our lab in developing diverse optofluidic devices using two unique configurations: thin-walled capillary based optofluidic ring resonator (OFRR) and multi-hole capillary based optofluidic platforms. The first one has been developed to be OFRR-based label-free biosensor, microfluidic laser based intra-cavity sensors, and on-column optical detectors for micro-gas chromatography (μGC), while the second one has been developed to be optofluidic Fabry-Pérot based label-free biosensor and optofluidic Surface-Enhanced Raman Spectroscopy (SERS) biosensor. All of these devices take advantage of superior fluidic handling capability and high sensitivity, and have been used in detecting various biological and chemical analytes in either liquid or vapor phase.

  5. Biochemically enhanced methane production from coal

    NASA Astrophysics Data System (ADS)

    Opara, Aleksandra

    For many years, biogas was connected mostly with the organic matter decomposition in shallow sediments (e.g., wetlands, landfill gas, etc.). Recently, it has been realized that biogenic methane production is ongoing in many hydrocarbon reservoirs. This research examined microbial methane and carbon dioxide generation from coal. As original contributions methane production from various coal materials was examined in classical and electro-biochemical bench-scale reactors using unique, developed facultative microbial consortia that generate methane under anaerobic conditions. Facultative methanogenic populations are important as all known methanogens are strict anaerobes and their application outside laboratory would be problematic. Additional testing examined the influence of environmental conditions, such as pH, salinity, and nutrient amendments on methane and carbon dioxide generation. In 44-day ex-situ bench-scale batch bioreactor tests, up to 300,000 and 250,000 ppm methane was generated from bituminous coal and bituminous coal waste respectively, a significant improvement over 20-40 ppm methane generated from control samples. Chemical degradation of complex hydrocarbons using environmentally benign reagents, prior to microbial biodegradation and methanogenesis, resulted in dissolution of up to 5% bituminous coal and bituminous coal waste and up to 25% lignite in samples tested. Research results confirm that coal waste may be a significant underutilized resource that could be converted to useful fuel. Rapid acidification of lignite samples resulted in low pH (below 4.0), regardless of chemical pretreatment applied, and did not generate significant methane amounts. These results confirmed the importance of monitoring and adjusting in situ and ex situ environmental conditions during methane production. A patented Electro-Biochemical Reactor technology was used to supply electrons and electron acceptor environments, but appeared to influence methane generation in a

  6. Thermodynamic constraints for biochemical networks.

    PubMed

    Beard, Daniel A; Babson, Eric; Curtis, Edward; Qian, Hong

    2004-06-07

    The constraint-based approach to analysis of biochemical systems has emerged as a useful tool for rational metabolic engineering. Flux balance analysis (FBA) is based on the constraint of mass conservation; energy balance analysis (EBA) is based on non-equilibrium thermodynamics. The power of these approaches lies in the fact that the constraints are based on physical laws, and do not make use of unknown parameters. Here, we show that the network structure (i.e. the stoichiometric matrix) alone provides a system of constraints on the fluxes in a biochemical network which are feasible according to both mass balance and the laws of thermodynamics. A realistic example shows that these constraints can be sufficient for deriving unambiguous, biologically meaningful results. The thermodynamic constraints are obtained by comparing of the sign pattern of the flux vector to the sign patterns of the cycles of the internal cycle space via connection between stoichiometric network theory (SNT) and the mathematical theory of oriented matroids.

  7. Bistability in biochemical signaling models.

    PubMed

    Sobie, Eric A

    2011-09-20

    This Teaching Resource provides lecture notes, slides, and a student assignment for a two-part lecture on the principles underlying bistability in biochemical signaling networks, which are illustrated with examples from the literature. The lectures cover analog, or graded, versus digital, all-or-none, responses in cells, with examples from different types of biological processes requiring each. Rate-balance plots are introduced as a method for determining whether generic one-variable systems exhibit one or several stable steady states. Bifurcation diagrams are presented as a more general method for detecting the presence of bistability in biochemical signaling networks. The examples include an artificial toggle switch, the lac operon in bacteria, and the mitogen-activated protein kinase cascade in both Xenopus oocytes and mammalian cells. The second part of the lecture links the concepts of bistability more closely to the mathematical tools provided by dynamical systems analysis. The examples from the first part of the lecture are analyzed with phase-plane techniques and bifurcation analysis, using the scientific programming language MATLAB. Using these programs as a template, the assignment requires the students to implement a model from the literature and analyze the stability of this model's steady states.

  8. Biochemical abnormalities in Pearson syndrome.

    PubMed

    Crippa, Beatrice Letizia; Leon, Eyby; Calhoun, Amy; Lowichik, Amy; Pasquali, Marzia; Longo, Nicola

    2015-03-01

    Pearson marrow-pancreas syndrome is a multisystem mitochondrial disorder characterized by bone marrow failure and pancreatic insufficiency. Children who survive the severe bone marrow dysfunction in childhood develop Kearns-Sayre syndrome later in life. Here we report on four new cases with this condition and define their biochemical abnormalities. Three out of four patients presented with failure to thrive, with most of them having normal development and head size. All patients had evidence of bone marrow involvement that spontaneously improved in three out of four patients. Unique findings in our patients were acute pancreatitis (one out of four), renal Fanconi syndrome (present in all patients, but symptomatic only in one), and an unusual organic aciduria with 3-hydroxyisobutyric aciduria in one patient. Biochemical analysis indicated low levels of plasma citrulline and arginine, despite low-normal ammonia levels. Regression analysis indicated a significant correlation between each intermediate of the urea cycle and the next, except between ornithine and citrulline. This suggested that the reaction catalyzed by ornithine transcarbamylase (that converts ornithine to citrulline) might not be very efficient in patients with Pearson syndrome. In view of low-normal ammonia levels, we hypothesize that ammonia and carbamylphosphate could be diverted from the urea cycle to the synthesis of nucleotides in patients with Pearson syndrome and possibly other mitochondrial disorders.

  9. Biochemical aspects of Huntington's chorea.

    PubMed Central

    Caraceni, T; Calderini, G; Consolazione, A; Riva, E; Algeri, S; Girotti, F; Spreafico, R; Branciforti, A; Dall'olio, A; Morselli, P L

    1977-01-01

    Fifteen patients affected by Huntington's chorea were divided into two groups, 'slow' and 'fast', according to IQ scores on the Wechsler-Bellevue scale, and scores on some motor performance tests. A possible correlation was looked for between some biochemical data (cerebrospinal fluid (CSF), homovanillic acid (HVA), and 5-hydroxyindolacetic acid (5HIAA) levels, plasma dopamine-beta-hydroxylase (DBH), dopamine (DA) uptake by platelets), and clinical data (duration of illness, severity of symptoms, age of patients, IQ scores, 'slow' and 'fast' groups). The CSF, HVA, and 5HIAA levels were found to be significantly lowered in comparison with normal controls. DBH activity and DA uptake by platelets did not differ significantly from normal subjects. Treatment with haloperidol in all patients and with dipropylacetic acid in three patients did not appear to modify the CSF, HVA, and 5HIAA concentrations, the plasma DBH activity, or the DA uptake. There were no significant differences in the CSF, HVA, and 5HIAA contents between the two groups of patients, and there was no correlation between biochemical data and clinical features. PMID:143508

  10. Diagnosis of hyperandrogenism: biochemical criteria.

    PubMed

    Stanczyk, Frank Z

    2006-06-01

    Biochemical derangements in ovarian, adrenal, and peripheral androgen production and metabolism play an important role in underlying causes of hyperandrogenism. Specific diagnostic serum markers such as testosterone (total) and dehydroepiandrosterone sulfate (DHEAS), respectively, may be helpful in the diagnosis of ovarian and adrenal hyperandrogenism, respectively. Validated immunoassays or mass spectrometry assays should be used to quantify testosterone, DHEAS and other principal androgens. Free testosterone measurements, determined by equilibrium dialysis or the calculated method, are advocated for routine evaluation of more subtle forms of hyperandrogenism. The skin, with its pilosebaceous units (PSUs), is an important site of active androgen production. A key regulator in PSUs is 5alpha-reductase, which transforms testosterone or androstenedione to dihydrotestosterone (DHT). DHT in blood is not effective in indicating the presence of hyperandrogenism. However, distal metabolites of DHT have been shown to be good markers of clinical manifestations of hirsutism, acne and alopecia. Assays for these peripheral markers need improvement for routine clinical testing.

  11. Biochemical nature of Russell Bodies

    PubMed Central

    Francesca Mossuto, Maria; Ami, Diletta; Anelli, Tiziana; Fagioli, Claudio; Maria Doglia, Silvia; Sitia, Roberto

    2015-01-01

    Professional secretory cells produce and release abundant proteins. Particularly in case of mutations and/or insufficient chaperoning, these can aggregate and become toxic within or amongst cells. Immunoglobulins (Ig) are no exception. In the extracellular space, certain Ig-L chains form fibrils causing systemic amyloidosis. On the other hand, Ig variants lacking the first constant domain condense in dilated cisternae of the early secretory compartment, called Russell Bodies (RB), frequently observed in plasma cell dyscrasias, autoimmune diseases and chronic infections. RB biogenesis can be recapitulated in lymphoid and non-lymphoid cells by expressing mutant Ig-μ, providing powerful models to investigate the pathophysiology of endoplasmic reticulum storage disorders. Here we analyze the aggregation propensity and the biochemical features of the intra- and extra-cellular Ig deposits in human cells, revealing β-aggregated features for RB. PMID:26223695

  12. Biochemical nature of Russell Bodies.

    PubMed

    Mossuto, Maria Francesca; Ami, Diletta; Anelli, Tiziana; Fagioli, Claudio; Doglia, Silvia Maria; Sitia, Roberto

    2015-07-30

    Professional secretory cells produce and release abundant proteins. Particularly in case of mutations and/or insufficient chaperoning, these can aggregate and become toxic within or amongst cells. Immunoglobulins (Ig) are no exception. In the extracellular space, certain Ig-L chains form fibrils causing systemic amyloidosis. On the other hand, Ig variants lacking the first constant domain condense in dilated cisternae of the early secretory compartment, called Russell Bodies (RB), frequently observed in plasma cell dyscrasias, autoimmune diseases and chronic infections. RB biogenesis can be recapitulated in lymphoid and non-lymphoid cells by expressing mutant Ig-μ, providing powerful models to investigate the pathophysiology of endoplasmic reticulum storage disorders. Here we analyze the aggregation propensity and the biochemical features of the intra- and extra-cellular Ig deposits in human cells, revealing β-aggregated features for RB.

  13. Biochemical Conversion: Using Enzymes, Microbes, and Catalysis to Make Fuels and Chemicals

    SciTech Connect

    2013-07-26

    This fact sheet describes the Bioenergy Technologies Office's biochemical conversion work and processes. BETO conducts collaborative research, development, and demonstration projects to improve several processing routes for the conversion of cellulosic biomass.

  14. [Biochemical genetics in St. Petersburg university: from the gene-enzyme model to medical biotechnology].

    PubMed

    Padkina, M V; Sambuk, E V

    2007-10-01

    The history of biochemical genetic research in St. Petersburg (Leningrad) State University is described. The main research projects and achievements of the Laboratory of Biochemical Genetics in studies on the mechanisms of gene expression control, coordinated regulation of metabolism, and the relationship of the physiological state of yeast cells with the maintenance of genetic stability are discussed. The fundamental importance of studies on the acid phosphatase model for the formation and development of medical biotechnology in St. Petersburg University is demonstrated.

  15. BioSM: metabolomics tool for identifying endogenous mammalian biochemical structures in chemical structure space.

    PubMed

    Hamdalla, Mai A; Mandoiu, Ion I; Hill, Dennis W; Rajasekaran, Sanguthevar; Grant, David F

    2013-03-25

    The structural identification of unknown biochemical compounds in complex biofluids continues to be a major challenge in metabolomics research. Using LC/MS, there are currently two major options for solving this problem: searching small biochemical databases, which often do not contain the unknown of interest or searching large chemical databases which include large numbers of nonbiochemical compounds. Searching larger chemical databases (larger chemical space) increases the odds of identifying an unknown biochemical compound, but only if nonbiochemical structures can be eliminated from consideration. In this paper we present BioSM; a cheminformatics tool that uses known endogenous mammalian biochemical compounds (as scaffolds) and graph matching methods to identify endogenous mammalian biochemical structures in chemical structure space. The results of a comprehensive set of empirical experiments suggest that BioSM identifies endogenous mammalian biochemical structures with high accuracy. In a leave-one-out cross validation experiment, BioSM correctly predicted 95% of 1388 Kyoto Encyclopedia of Genes and Genomes (KEGG) compounds as endogenous mammalian biochemicals using 1565 scaffolds. Analysis of two additional biological data sets containing 2330 human metabolites (HMDB) and 2416 plant secondary metabolites (KEGG) resulted in biochemical annotations of 89% and 72% of the compounds, respectively. When a data set of 3895 drugs (DrugBank and USAN) was tested, 48% of these structures were predicted to be biochemical. However, when a set of synthetic chemical compounds (Chembridge and Chemsynthesis databases) were examined, only 29% of the 458,207 structures were predicted to be biochemical. Moreover, BioSM predicted that 34% of 883,199 randomly selected compounds from PubChem were biochemical. We then expanded the scaffold list to 3927 biochemical compounds and reevaluated the above data sets to determine whether scaffold number influenced model performance

  16. Back to basics: thermodynamics in biochemical engineering.

    PubMed

    von Stockar, U; van der Wielen, L A M

    2003-01-01

    Rational and efficient process development in chemical technology always makes heavy use of process analysis in terms of balances, kinetics, and thermodynamics. While the first two of these concepts have been extensively used in biotechnology, it appears that thermodynamics has received relatively little attention from biotechnologists. This state of affairs is one among several reasons why development and design of biotechnological processes is today mostly carried out in an essentially empirical fashion and why bioprocesses are often not as thoroughly optimized as many chemical processes. Since quite a large body of knowledge in the area of bio thermodynamics already existed in the early nineties, the Steering Committee of a European Science Foundation program on Process Integration in Biochemical Engineering identified a need to stimulate a more systematic use of thermodynamics in the area. To this effect, a bianual course for advanced graduate students and researchers was developed. The present contribution uses the course structure to provide an outline of the area and to characterize very briefly the achievements, the challenges, and the research needs in the various sub-topics.

  17. The role of thermodynamics in biochemical engineering

    NASA Astrophysics Data System (ADS)

    von Stockar, Urs

    2013-09-01

    This article is an adapted version of the introductory chapter of a book whose publication is imminent. It bears the title "Biothermodynamics - The role of thermodynamics in biochemical engineering." The aim of the paper is to give a very short overview of the state of biothermodynamics in an engineering context as reflected in this book. Seen from this perspective, biothermodynamics may be subdivided according to the scale used to formalize the description of the biological system into three large areas: (i) biomolecular thermodynamics (most fundamental scale), (ii) thermodynamics of metabolism (intermediary scale), and (iii) whole-cell thermodynamics ("black-box" description of living entities). In each of these subareas, the main available theoretical approaches and the current and the potential applications are discussed. Biomolecular thermodynamics (i) is especially well developed and is obviously highly pertinent for the development of downstream processing. Its use ought to be encouraged as much as possible. The subarea of thermodynamics of live cells (iii), although scarcely applied in practice, is also expected to enhance bioprocess research and development, particularly in predicting culture performances, for understanding the driving forces for cellular growth, and in developing, monitoring, and controlling cellular cultures. Finally, there is no question that thermodynamic analysis of cellular metabolism (ii) is a promising tool for systems biology and for many other applications, but quite a large research effort is still needed before it may be put to practical use.

  18. Associative learning in biochemical networks.

    PubMed

    Gandhi, Nikhil; Ashkenasy, Gonen; Tannenbaum, Emmanuel

    2007-11-07

    It has been recently suggested that there are likely generic features characterizing the emergence of systems constructed from the self-organization of self-replicating agents acting under one or more selection pressures. Therefore, structures and behaviors at one length scale may be used to infer analogous structures and behaviors at other length scales. Motivated by this suggestion, we seek to characterize various "animate" behaviors in biochemical networks, and the influence that these behaviors have on genomic evolution. Specifically, in this paper, we develop a simple, chemostat-based model illustrating how a process analogous to associative learning can occur in a biochemical network. Associative learning is a form of learning whereby a system "learns" to associate two stimuli with one another. Associative learning, also known as conditioning, is believed to be a powerful learning process at work in the brain (associative learning is essentially "learning by analogy"). In our model, two types of replicating molecules, denoted as A and B, are present in some initial concentration in the chemostat. Molecules A and B are stimulated to replicate by some growth factors, denoted as G(A) and G(B), respectively. It is also assumed that A and B can covalently link, and that the conjugated molecule can be stimulated by either the G(A) or G(B) growth factors (and can be degraded). We show that, if the chemostat is stimulated by both growth factors for a certain time, followed by a time gap during which the chemostat is not stimulated at all, and if the chemostat is then stimulated again by only one of the growth factors, then there will be a transient increase in the number of molecules activated by the other growth factor. Therefore, the chemostat bears the imprint of earlier, simultaneous stimulation with both growth factors, which is indicative of associative learning. It is interesting to note that the dynamics of our model is consistent with certain aspects of

  19. Biochemical markers of spontaneous preterm birth in asymptomatic women.

    PubMed

    Chan, Ronna L

    2014-01-01

    Preterm birth is a delivery that occurs at less than 37 completed weeks of gestation and it is associated with perinatal morbidity and mortality. Spontaneous preterm birth accounts for up to 75% of all preterm births. A number of maternal or fetal characteristics have been associated with preterm birth, but the use of individual or group biochemical markers have advanced some of the understanding on the mechanisms leading to spontaneous preterm birth. This paper provides a summary on the current literature on the use of biochemical markers in predicting spontaneous preterm birth in asymptomatic women. Evidence from the literature suggests fetal fibronectin, cervical interleukin-6, and α-fetoprotein as promising biochemical markers in predicting spontaneous preterm birth in asymptomatic women. The role of gene-gene and gene-environment interactions, as well as epigenetics, has the potential to further elucidate and improve understanding of the underlying mechanisms or pathways of spontaneous preterm birth. Refinement in study design and methodology is needed in future research for the development and validation of individual or group biochemical marker(s) for use independently or in conjunction with other potential risk factors such as genetic variants and environmental and behavioral factors in predicting spontaneous preterm birth across diverse populations.

  20. Serum Biochemical Phenotypes in the Domestic Dog.

    PubMed

    Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A

    2016-01-01

    The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species.

  1. Biochemical transformation of solid carbonaceous material

    DOEpatents

    Lin, Mow S.; Premuzic, Eugene T.

    2001-09-25

    A method of biochemically transforming macromolecular compounds found in solid carbonaceous materials, such as coal is provided. The preparation of new microorganisms, metabolically weaned through challenge growth processes to biochemically transform solid carbonaceous materials at extreme temperatures, pressures, pH, salt and toxic metal concentrations is also disclosed.

  2. Serum Biochemical Phenotypes in the Domestic Dog

    PubMed Central

    Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A.

    2016-01-01

    The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species. PMID:26919479

  3. Within-Person Covariation between Mood and Biochemicals.

    DTIC Science & Technology

    1980-01-01

    experiments. Journal of Personality and Social Psychology , 37, 989-995. Vickers, R.R., Jr. (1979). The relationship of psychological coping and defenses to... Personality and Social Psychology , 10, 406-413. Si 15. Table 1. Average Within- Person Correlations Between Moods Act. Ang. Hap. Fear Dep. Fat...I AD-A158 196 WITHIN- PERSON COVARIATION BETWEEN MOOD AND BIOCHEMICALS III (U) NAVAL HEALTH RESEARCH CENTER SAN DIEGO CA I R R VICKERS ET AL. 1989

  4. Biochemical genetic markers in sugarcane.

    PubMed

    Glaszmann, J C; Fautret, A; Noyer, J L; Feldmann, P; Lanaud, C

    1989-10-01

    Isozyme variation was used to identify biochemical markers of potential utility in sugarcane genetics and breeding. Electrophoretic polymorphism was surveyed for nine enzymes among 39 wild and noble sugarcane clones, belonging to the species most closely related to modern varieties. Up to 114 distinct bands showing presence versus absence type of variation were revealed and used for qualitative characterization of the materials. Multivariate analysis of the data isolated the Erianthus clone sampled and separated the Saccharum spontaneum clones from the S. robustum and S. officinarum clones; the latter two were not differentiated from one another. The analysis of self-progenies of a 2n=112 S. spontaneum and of a commercial variety showed examples of mono- and polyfactorial segregations. Within the progeny of the variety, co-segregation of two isozymes frequent in S. spontaneum led to them being assigned to a single chromosome initially contributed by a S. spontaneum donor. This illustrates how combined survey of ancestral species and segregation analysis in modern breeding materials should permit using the lack of interspecific cross-over to establish linkage groups in a sugarcane genome.

  5. An Integrated Qualitative and Quantitative Biochemical Model Learning Framework Using Evolutionary Strategy and Simulated Annealing.

    PubMed

    Wu, Zujian; Pang, Wei; Coghill, George M

    Both qualitative and quantitative model learning frameworks for biochemical systems have been studied in computational systems biology. In this research, after introducing two forms of pre-defined component patterns to represent biochemical models, we propose an integrative qualitative and quantitative modelling framework for inferring biochemical systems. In the proposed framework, interactions between reactants in the candidate models for a target biochemical system are evolved and eventually identified by the application of a qualitative model learning approach with an evolution strategy. Kinetic rates of the models generated from qualitative model learning are then further optimised by employing a quantitative approach with simulated annealing. Experimental results indicate that our proposed integrative framework is feasible to learn the relationships between biochemical reactants qualitatively and to make the model replicate the behaviours of the target system by optimising the kinetic rates quantitatively. Moreover, potential reactants of a target biochemical system can be discovered by hypothesising complex reactants in the synthetic models. Based on the biochemical models learned from the proposed framework, biologists can further perform experimental study in wet laboratory. In this way, natural biochemical systems can be better understood.

  6. Genetics Home Reference: Wiskott-Aldrich syndrome

    MedlinePlus

    ... Syndrome: a model for defective actin reorganization, cell trafficking and synapse formation. Curr Opin Immunol. 2003 Oct; ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of ...

  7. Accurate atom-mapping computation for biochemical reactions.

    PubMed

    Latendresse, Mario; Malerich, Jeremiah P; Travers, Mike; Karp, Peter D

    2012-11-26

    The complete atom mapping of a chemical reaction is a bijection of the reactant atoms to the product atoms that specifies the terminus of each reactant atom. Atom mapping of biochemical reactions is useful for many applications of systems biology, in particular for metabolic engineering where synthesizing new biochemical pathways has to take into account for the number of carbon atoms from a source compound that are conserved in the synthesis of a target compound. Rapid, accurate computation of the atom mapping(s) of a biochemical reaction remains elusive despite significant work on this topic. In particular, past researchers did not validate the accuracy of mapping algorithms. We introduce a new method for computing atom mappings called the minimum weighted edit-distance (MWED) metric. The metric is based on bond propensity to react and computes biochemically valid atom mappings for a large percentage of biochemical reactions. MWED models can be formulated efficiently as Mixed-Integer Linear Programs (MILPs). We have demonstrated this approach on 7501 reactions of the MetaCyc database for which 87% of the models could be solved in less than 10 s. For 2.1% of the reactions, we found multiple optimal atom mappings. We show that the error rate is 0.9% (22 reactions) by comparing these atom mappings to 2446 atom mappings of the manually curated Kyoto Encyclopedia of Genes and Genomes (KEGG) RPAIR database. To our knowledge, our computational atom-mapping approach is the most accurate and among the fastest published to date. The atom-mapping data will be available in the MetaCyc database later in 2012; the atom-mapping software will be available within the Pathway Tools software later in 2012.

  8. Reaction networks and kinetics of biochemical systems.

    PubMed

    Arceo, Carlene Perpetua P; Jose, Editha C; Lao, Angelyn R; Mendoza, Eduardo R

    2017-01-01

    This paper further develops the connection between Chemical Reaction Network Theory (CRNT) and Biochemical Systems Theory (BST) that we recently introduced [1]. We first use algebraic properties of kinetic sets to study the set of complex factorizable kinetics CFK(N) on a CRN, which shares many characteristics with its subset of mass action kinetics. In particular, we extend the Theorem of Feinberg-Horn [9] on the coincidence of the kinetic and stoichiometric subsets of a mass action system to CF kinetics, using the concept of span surjectivity. We also introduce the branching type of a network, which determines the availability of kinetics on it and allows us to characterize the networks for which all kinetics are complex factorizable: A "Kinetics Landscape" provides an overview of kinetics sets, their algebraic properties and containment relationships. We then apply our results and those (of other CRNT researchers) reviewed in [1] to fifteen BST models of complex biological systems and discover novel network and kinetic properties that so far have not been widely studied in CRNT. In our view, these findings show an important benefit of connecting CRNT and BST modeling efforts. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Biochemical studies of the tracheobronchial epithelium

    SciTech Connect

    Mass, M.J.; Kaufman, D.G.

    1984-06-01

    Tracheobronchial epithelium has been a focus of intense investigation in the field of chemical carcinogenesis. We have reviewed some biochemical investigations that have evolved through linkage with carcinogenesis research. These areas of investigation have included kinetics of carcinogen metabolism, identification of carcinogen metabolites, levels of carcinogen binding to DNA, and analysis of carcinogen-DNA adducts. Such studies appear to have provided a reasonable explanation for the susceptibilities of the respiratory tracts of rats and hamsters to carcinogenesis by benzo(a)pyrene. Coinciding with the attempts to understand the initiation of carcinogenesis in the respiratory tract has also been a major thrust aimed at effecting its prevention both in humans and in animal models for human bronchogenic carcinoma. These studies have concerned the effects of derivatives of vitamin A (retinoids) and their influence on normal cell biology and biochemistry of this tissue. Recent investigations have included the effects of retinoid deficiency on the synthesis of RNA and the identification of RNA species associated with this biological state, and also have included the effects of retinoids on the synthesis of mucus-related glycoproteins. Tracheal organ cultures from retinoid-deficient hamsters have been used successfully to indicate the potency of synthetic retinoids by monitoring the reversal of squamous metaplasia. Techniques applied to this tissue have also served to elucidate features of the metabolism of retinoic acid using high pressure liquid chromatography. 94 references, 9 figures, 2 tables.

  10. PHA bioplastics, biochemicals, and energy from crops.

    PubMed

    Somleva, Maria N; Peoples, Oliver P; Snell, Kristi D

    2013-02-01

    Large scale production of polyhydroxyalkanoates (PHAs) in plants can provide a sustainable supply of bioplastics, biochemicals, and energy from sunlight and atmospheric CO(2). PHAs are a class of polymers with various chain lengths that are naturally produced by some microorganisms as storage materials. The properties of these polyesters make them functionally equivalent to many of the petroleum-based plastics that are currently in the market place. However, unlike most petroleum-derived plastics, PHAs can be produced from renewable feedstocks and easily degrade in most biologically active environments. This review highlights research efforts over the last 20 years to engineer the production of PHAs in plants with a focus on polyhydroxybutryrate (PHB) production in bioenergy crops with C(4) photosynthesis. PHB has the potential to be a high volume commercial product with uses not only in the plastics and materials markets, but also in renewable chemicals and feed. The major challenges of improving product yield and plant fitness in high biomass yielding C(4) crops are discussed in detail. Plant Biotechnology Journal © 2013 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  11. [Biochemical aspects of chronic rheumatic inflammation].

    PubMed

    Delbrück, A

    1975-01-01

    Morphological phenomena in rheumatoid arthritis are closely correlated to the biochemical aberrations of connective tissue metabolism. Both, morphological and biochemical analysis of the altered tissue portions demonstrate evidence for uncontrolled proliferation resp. metabolism similar to human and experimental malignoma. The present state of biochemical knowledge in this field permits to describe the metabolic state of the afflicted tissue by means of enzyme activity and substrate pattern and to draw some conclusions in respect to the pathogenesis of inflammatory processes involved in chronic rheumatic diseases.

  12. Thin-Film Transistor-Based Biosensors for Determining Stoichiometry of Biochemical Reactions

    PubMed Central

    Wang, Yi-Wen; Chen, Ting-Yang; Yang, Tsung-Han; Chang, Cheng-Chung; Yang, Tsung-Lin; Lo, Yu-Hwa

    2016-01-01

    The enzyme kinetic in a biochemical reaction is critical to scientific research and drug discovery but can hardly be determined experimentally from enzyme assays. In this work, a charge-current transducer (a transistor) is proposed to evaluate the status of biochemical reaction by monitoring the electrical charge changes. Using the malate-aspartate shuttle as an example, a thin-film transistor (TFT)-based biosensor with an extended gold pad is demonstrated to detect the biochemical reaction between NADH and NAD+. The drain current change indicates the status of chemical equilibrium and stoichiometry. PMID:28033412

  13. Thin-Film Transistor-Based Biosensors for Determining Stoichiometry of Biochemical Reactions.

    PubMed

    Wang, Yi-Wen; Chen, Ting-Yang; Yang, Tsung-Han; Chang, Cheng-Chung; Yang, Tsung-Lin; Lo, Yu-Hwa; Huang, Jian-Jang

    2016-01-01

    The enzyme kinetic in a biochemical reaction is critical to scientific research and drug discovery but can hardly be determined experimentally from enzyme assays. In this work, a charge-current transducer (a transistor) is proposed to evaluate the status of biochemical reaction by monitoring the electrical charge changes. Using the malate-aspartate shuttle as an example, a thin-film transistor (TFT)-based biosensor with an extended gold pad is demonstrated to detect the biochemical reaction between NADH and NAD+. The drain current change indicates the status of chemical equilibrium and stoichiometry.

  14. Changes in biochemical and functional parameters for men during exercise

    PubMed Central

    Karanauskiene, Diana; Zaicenkoviene, Kristina; Stasiule, Loreta

    2015-01-01

    Benefits of physical activity are undeniable. The aim of the present research was to determine the effects of physical activity and age on cholesterol and glucose levels in the blood, as well as changes in the functional parameters of the cardiovascular system, during stepwise increases in physical load for men employed in the same place, but with different levels of physical activity. The subjects were 95 military officers who were divided into groups according to the level of physical activity of their occupation, with veloergometry used as physical load. Cholesterol and glucose levels in the blood were taken as biochemical indices. The results showed that occupational physical activity had a positive effect on biochemical and cardiovascular functional parameters before, during, and after the physical load. Only the cardiovascular rate (systolic blood pressure) in older subjects was significantly higher than that of the younger persons; for all other parameters, age had no effect at all. PMID:28352696

  15. [Progress in noninvasive biochemical examination by near infrared spectroscopy].

    PubMed

    Ding, Hai-quan; Lu, Qi-peng; Peng, Zhong-qi; Chen, Xing-dan

    2010-08-01

    In the early nineties of last century, great importance had been gradually attached to the potential of near-infrared spectroscopy (NIRS) in the human body noninvasive biochemical examination. However, the human body is extremely complex. Although research teams have made some achievements in experimental simulations and in-vitro analysis, there is still no substantive breakthrough in clinical application now. The present paper discusses the key problems which prevent NIRS from achieving human noninvasive clinical biochemical examination, such as weak signal, the interference of human tissue background and the problem of blood volume change. The thoughts of noninvasive biomedical examination using NIRS are divided into two categories in terms of analytical method, that is classical near-infrared analysis and issue background interference elimination analysis. This paper also introduces in detail the current status of the two categories in the world, and believes that the second category is more promising to be successful in clinical application under the existing conditions.

  16. [Biochemical aspects of fetal hypoxia].

    PubMed

    Biringer, K; Danko, J; Dókus, K; Mat'asová, K; Zibolen, M; Pullmann, R

    2011-09-01

    To evaluate validity of biochemical diagnostic methods of fetal hypoxia. A case-control study. Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic. We included 67 patients, and they were retrospectively divided into group of controls (n=36), and studied group (n=31) according to pH in umbilical artery (UA) <7.15. Acid-base parameters were assessed with Rapidlab 248, Bayer Healthcare LLC, East Walpole, USA. We determined criterion for metabolic acidosis (MAC) as pH UA <7.15, resp. base deficit (BD) UA >12 mmol/l. Postpartal lactate concentration in umbilical vein (UV) and UA was determined with lactatemeter Accutrend Lactate, Roche Diagnostics, Switzerland. Quantitative assessment of fetal human protein S100B was provided with ELISA (Sangtec 100 ELISA, DiaSorin Inc., Stillwater, Minnesota, USA). Fetal erythropoietin concentration in UV was examined with immunoenzymatic assessment Access EPO (Beckman Coulter, Inc., Fullerton, CA, USA). histograms, Kolmogorov-Smirnov test, Mann-Whitney test, Spearman's rho; statistical significance: p<0.05, Receiver Operating Characteristic curves, Area Under the Curve. The best correlation was between fetal acid-base parameters and lactate in UA (p<0.0005). Significant correlation was between EPO in UV, and protein S100B in UV (p<0.05). EPO in UV significantly correlated with lactate in UA (p<0.05). Correlation between EPO in UV and protein S100B was not significant. According to ROC curves in prediction of fetal hypoxia, we found an excellent accuracy (AUC>0.9) for lactate in UA, good accuracy (AUC>0.7) had EPO in UV. Results for protein S100B were not significant. The highest sensitivity had EPO in UV, while the highest specificity has had lactate in UA. An indisputable evidence of labor management quality is the fetal metabolic status. On the basis of our results, the suitable clinical markers are lactate and EPO, in addition to acid-base parameters.

  17. Biochemical thermodynamics: applications of Mathematica.

    PubMed

    Alberty, Robert A

    2006-01-01

    reactants. Thus loading this package makes available 774 mathematical functions for these properties. These functions can be added and subtracted to obtain changes in these properties in biochemical reactions and apparent equilibrium constants.

  18. Raman spectroscopic biochemical mapping of tissues

    NASA Astrophysics Data System (ADS)

    Stone, Nicholas; Hart Prieto, Maria C.; Kendall, Catherine A.; Shetty, Geeta; Barr, Hugh

    2006-02-01

    Advances in technologies have brought us closer to routine spectroscopic diagnosis of early malignant disease. However, there is still a poor understanding of the carcinogenesis process. For example it is not known whether many cancers follow a logical sequence from dysplasia, to carcinoma in situ, to invasion. Biochemical tissue changes, triggered by genetic mutations, precede morphological and structural changes. These can be probed using Raman or FTIR microspectroscopy and the spectra analysed for biochemical constituents. Local microscopic distribution of various constituents can then be visualised. Raman mapping has been performed on a number of tissues including oesophagus, breast, bladder and prostate. The biochemical constituents have been calculated at each point using basis spectra and least squares analysis. The residual of the least squares fit indicates any unfit spectral components. The biochemical distribution will be compared with the defined histopathological boundaries. The distribution of nucleic acids, glycogen, actin, collagen I, III, IV, lipids and others appear to follow expected patterns.

  19. Biochemical Lab Activity Supports Evolution Theory

    ERIC Educational Resources Information Center

    Dyman, Daniel J.

    1974-01-01

    Described is thin-layer chromatography (TLC), a technique that can be conveniently used in the laboratory to generate evidence supporting the principle that degrees of biochemical similarity reflect degrees of evolutionary relatedness among organisms. (Author/PEB)

  20. Biochemical Lab Activity Supports Evolution Theory

    ERIC Educational Resources Information Center

    Dyman, Daniel J.

    1974-01-01

    Described is thin-layer chromatography (TLC), a technique that can be conveniently used in the laboratory to generate evidence supporting the principle that degrees of biochemical similarity reflect degrees of evolutionary relatedness among organisms. (Author/PEB)

  1. Exploring the remote sensing of foliar biochemical concentrations with AVIRIS data

    NASA Technical Reports Server (NTRS)

    Smith, Geoffrey M.; Curran, Paul J.

    1992-01-01

    Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) data shows promise for the estimation of foliar biochemical concentrations at the scale of the canopy. There are, however, several problems associated with the use of AVIRIS data in this way and these are detailed in recent Plant Biochemical Workshop Report. The research reported was concentrated upon three of these problems: field sampling of forest canopies, wet laboratory assay of foliar chemicals, and the visualization of AVIRIS data.

  2. Biochemical-Pathway Diversity in Archaebacteria

    DTIC Science & Technology

    1990-08-30

    characteristic of much or all of the Gram-positive lineage of eubacteria . We have extended the enzymological base of information to include organisms...to compare the biochemical diversitv within the archaebacteria to the biochemical diversity already known or now emerging within the eubacteria . RAI...INALL: In eubacteria aromatic-pathway character states are exceedingly diverse. A given feature will cluster at a hierarchical level ot phylogeny that

  3. [Biochemical diagnostics of fatal opium intoxication].

    PubMed

    Papyshev, I P; Astashkina, O G; Tuchik, E S; Nikolaev, B S; Cherniaev, A L

    2013-01-01

    Biochemical diagnostics of fatal opium intoxication remains a topical problem in forensic medical science and practice. We investigated materials obtained in the course of forensic medical expertise of the cases of fatal opium intoxication. The study revealed significant differences between myoglobin levels in blood, urine, myocardium, and skeletal muscles. The proposed approach to biochemical diagnostics of fatal opium intoxication enhances the accuracy and the level of evidence of expert conclusions.

  4. Biochemical Education East and West.

    ERIC Educational Resources Information Center

    Biochemical Education, 1987

    1987-01-01

    Reports on a workshop held in Japan by the Committee of Education of the International Union of Biochemistry. Discusses some of the success of biochemistry in Japan. Describes the day-by-day schedule of the workshop and emphasizes the undergraduate, graduate, and research program in Japan. (TW)

  5. Biochemical Remediation Using Plant Enzymes

    DTIC Science & Technology

    1994-06-01

    landowners. (C.N. Smith, 706-546-3175) Assessing Soil Carbon Policies The goal of EPA’s BIOME Agroecosystems Assessment Project, which is part of the...Global Climate Change Research Program, is to evaluate the degree to which agroecosystems can be technically managed, on a sustainable basis, to conserve

  6. Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs – an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research

    PubMed Central

    2013-01-01

    In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [H+]-related mechanism underlying the initiation and progression of the neoplastic process has been recently described by different research groups as a new paradigm in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (↑pHi/↓pHe, or “proton reversal”). Tumor cells survive their hostile microenvironment due to membrane-bound proton pumps and transporters, and their main defensive strategy is to never allow internal acidification because that could lead to their death through apoptosis. In this context, one of the primary and best studied regulators of both pHi and pHe in tumors is the Na+/H+ exchanger isoform 1 (NHE1). An elevated NHE1 activity can be correlated with both an increase in cell pH and a decrease in the extracellular pH of tumors, and such proton reversal is associated with the origin, local growth, activation and further progression of the metastatic process. Consequently, NHE1 pharmaceutical inhibition by new and potent NHE1 inhibitors represents a potential and highly selective target in anticancer therapy. Cariporide, being one of the better studied specific and powerful NHE1 inhibitors, has proven to be well tolerated by humans in the cardiological context, however some side-effects, mainly related to drug accumulation and cerebrovascular complications were reported. Thus, cariporide could become a new, slightly toxic and effective anticancer agent in different human malignancies. PMID:24195657

  7. Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs--an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research.

    PubMed

    Harguindey, Salvador; Arranz, Jose Luis; Polo Orozco, Julian David; Rauch, Cyril; Fais, Stefano; Cardone, Rosa Angela; Reshkin, Stephan J

    2013-11-06

    In recent years an increasing number of publications have emphasized the growing importance of hydrogen ion dynamics in modern cancer research, from etiopathogenesis and treatment. A proton [H+]-related mechanism underlying the initiation and progression of the neoplastic process has been recently described by different research groups as a new paradigm in which all cancer cells and tissues, regardless of their origin and genetic background, have a pivotal energetic and homeostatic disturbance of their metabolism that is completely different from all normal tissues: an aberrant regulation of hydrogen ion dynamics leading to a reversal of the pH gradient in cancer cells and tissues (↑pHi/↓pHe, or "proton reversal"). Tumor cells survive their hostile microenvironment due to membrane-bound proton pumps and transporters, and their main defensive strategy is to never allow internal acidification because that could lead to their death through apoptosis. In this context, one of the primary and best studied regulators of both pHi and pHe in tumors is the Na+/H+ exchanger isoform 1 (NHE1). An elevated NHE1 activity can be correlated with both an increase in cell pH and a decrease in the extracellular pH of tumors, and such proton reversal is associated with the origin, local growth, activation and further progression of the metastatic process. Consequently, NHE1 pharmaceutical inhibition by new and potent NHE1 inhibitors represents a potential and highly selective target in anticancer therapy. Cariporide, being one of the better studied specific and powerful NHE1 inhibitors, has proven to be well tolerated by humans in the cardiological context, however some side-effects, mainly related to drug accumulation and cerebrovascular complications were reported. Thus, cariporide could become a new, slightly toxic and effective anticancer agent in different human malignancies.

  8. Causal correlation of foliar biochemical concentrations with AVIRIS spectra using forced entry linear regression

    NASA Technical Reports Server (NTRS)

    Dawson, Terence P.; Curran, Paul J.; Kupiec, John A.

    1995-01-01

    A major goal of airborne imaging spectrometry is to estimate the biochemical composition of vegetation canopies from reflectance spectra. Remotely-sensed estimates of foliar biochemical concentrations of forests would provide valuable indicators of ecosystem function at regional and eventually global scales. Empirical research has shown a relationship exists between the amount of radiation reflected from absorption features and the concentration of given biochemicals in leaves and canopies (Matson et al., 1994, Johnson et al., 1994). A technique commonly used to determine which wavelengths have the strongest correlation with the biochemical of interest is unguided (stepwise) multiple regression. Wavelengths are entered into a multivariate regression equation, in their order of importance, each contributing to the reduction of the variance in the measured biochemical concentration. A significant problem with the use of stepwise regression for determining the correlation between biochemical concentration and spectra is that of 'overfitting' as there are significantly more wavebands than biochemical measurements. This could result in the selection of wavebands which may be more accurately attributable to noise or canopy effects. In addition, there is a real problem of collinearity in that the individual biochemical concentrations may covary. A strong correlation between the reflectance at a given wavelength and the concentration of a biochemical of interest, therefore, may be due to the effect of another biochemical which is closely related. Furthermore, it is not always possible to account for potentially suitable waveband omissions in the stepwise selection procedure. This concern about the suitability of stepwise regression has been identified and acknowledged in a number of recent studies (Wessman et al., 1988, Curran, 1989, Curran et al., 1992, Peterson and Hubbard, 1992, Martine and Aber, 1994, Kupiec, 1994). These studies have pointed to the lack of a physical

  9. Complete integrability of information processing by biochemical reactions

    NASA Astrophysics Data System (ADS)

    Agliari, Elena; Barra, Adriano; Dello Schiavo, Lorenzo; Moro, Antonio

    2016-11-01

    Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling – based on spin systems – has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis–Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy – based on completely integrable hydrodynamic-type systems of PDEs – which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions.

  10. Complete integrability of information processing by biochemical reactions

    PubMed Central

    Agliari, Elena; Barra, Adriano; Dello Schiavo, Lorenzo; Moro, Antonio

    2016-01-01

    Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. Within such framework far-reaching analogies are established among (anti-) cooperative collective behaviors in chemical kinetics, (anti-)ferromagnetic spin models in statistical mechanics and operational amplifiers/flip-flops in cybernetics. The underlying modeling – based on spin systems – has been proved to be accurate for a wide class of systems matching classical (e.g. Michaelis–Menten, Hill, Adair) scenarios in the infinite-size approximation. However, the current research in biochemical information processing has been focusing on systems involving a relatively small number of units, where this approximation is no longer valid. Here we show that the whole statistical mechanical description of reaction kinetics can be re-formulated via a mechanical analogy – based on completely integrable hydrodynamic-type systems of PDEs – which provides explicit finite-size solutions, matching recently investigated phenomena (e.g. noise-induced cooperativity, stochastic bi-stability, quorum sensing). The resulting picture, successfully tested against a broad spectrum of data, constitutes a neat rationale for a numerically effective and theoretically consistent description of collective behaviors in biochemical reactions. PMID:27812018

  11. Medical treatment for biochemical relapse after radiotherapy.

    PubMed

    Quero, L; Hennequin, C

    2014-10-01

    This article's purpose was to review the medical data justifying the use of a medical treatment for biochemical relapse after external beam radiotherapy. The MEDLINE database was searched to identify relevant information with the following medical subject headings: "prostate cancer", "radiotherapy" and "biochemical relapse". Prognostic factors affecting the overall survival of patients with a biochemical relapse after external beam radiotherapy have been identified: short prostate specific antigen (PSA)-doubling time (< 12 months), high PSA value (> 10 ng/mL) and short interval between treatment and biochemical relapse (< 18 months). If a second local treatment is not feasible, timing to initiate a salvage medical treatment is not defined. Particularly, randomized trials did not demonstrate a significant benefit of an early initiation of androgen deprivation treatment. Some retrospective studies suggest that an early androgen deprivation is justified if poor prognostic factors are found. However, if an androgen deprivation treatment is prescribed, intermittent schedule is non-inferior to a continuous administration and seems to offer a better quality of life. Many non-hormonal treatments have also been evaluated in this setting: only 5-alpha-reductase inhibitors could be proposed in some specific situations. In conclusion, the judicious use of a medical treatment for biochemical relapse is still debated. Given the natural history of this clinical situation, a simple surveillance is justified in many cases.

  12. Nonlinear biochemical signal processing via noise propagation

    NASA Astrophysics Data System (ADS)

    Kim, Kyung Hyuk; Qian, Hong; Sauro, Herbert M.

    2013-10-01

    Single-cell studies often show significant phenotypic variability due to the stochastic nature of intra-cellular biochemical reactions. When the numbers of molecules, e.g., transcription factors and regulatory enzymes, are in low abundance, fluctuations in biochemical activities become significant and such "noise" can propagate through regulatory cascades in terms of biochemical reaction networks. Here we develop an intuitive, yet fully quantitative method for analyzing how noise affects cellular phenotypes based on identifying a system's nonlinearities and noise propagations. We observe that such noise can simultaneously enhance sensitivities in one behavioral region while reducing sensitivities in another. Employing this novel phenomenon we designed three biochemical signal processing modules: (a) A gene regulatory network that acts as a concentration detector with both enhanced amplitude and sensitivity. (b) A non-cooperative positive feedback system, with a graded dose-response in the deterministic case, that serves as a bistable switch due to noise-induced ultra-sensitivity. (c) A noise-induced linear amplifier for gene regulation that requires no feedback. The methods developed in the present work allow one to understand and engineer nonlinear biochemical signal processors based on fluctuation-induced phenotypes.

  13. Biochemical Abnormalities in Psychiatric Outpatients

    PubMed Central

    Lipman, Daniel G.; Collins, James L.; Mathura, Clyde B.; Elder, Zelda B.

    1984-01-01

    This research project was an outgrowth of the observations of the senior author over a period exceeding four decades of practice, teaching, and research as internist and psychiatrist, with primary emphasis on relationships between psyche and soma. Patients at the Outpatient Psychiatric Clinic of the Howard University Hospital, Washington, DC, were given thorough annual physical examinations and laboratory evaluations of blood and urine. The authors found a significantly high incidence of medical illnesses and abnormal laboratory findings not previously suspected. There was a significant and direct correlation between psychopathology as projected in the Lipman Personality Image Projection (LPIP) test and abnormal laboratory and physical findings. The results in this study concur with previous reports that so-called purely psychogenic stress symptoms may be related to unrecognized medical illnesses. These somatic illnesses may remain unrecognized for indefinite periods of time in the traditional psychiatric outpatient setting from which patients are often referred elsewhere for treatment of nonpsychiatric illness. Initial and periodic physical and laboratory examinations should be performed by psychiatrists trained to recognize nonpsychiatric diseases that often present with psychiatric symptoms. A thorough knowledge of the mind-body relationship is essential to the practice of modern psychiatry. PMID:6716498

  14. 40 CFR 158.2000 - Biochemical pesticides definition and applicability.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Biochemical pesticides definition and...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs (a...

  15. 40 CFR 158.2010 - Biochemical pesticides data requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Biochemical pesticides data...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2010 Biochemical pesticides... required to support registration of biochemical pesticides. Sections 158.2080 through 158.2084 identify the...

  16. 40 CFR 158.2000 - Biochemical pesticides definition and applicability.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Biochemical pesticides definition and...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs (a...

  17. 40 CFR 158.2010 - Biochemical pesticides data requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Biochemical pesticides data...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2010 Biochemical pesticides... required to support registration of biochemical pesticides. Sections 158.2080 through 158.2084 identify the...

  18. 40 CFR 158.2000 - Biochemical pesticides definition and applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Biochemical pesticides definition and...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs (a...

  19. 40 CFR 158.2000 - Biochemical pesticides definition and applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Biochemical pesticides definition and...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs (a...

  20. 40 CFR 158.2010 - Biochemical pesticides data requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Biochemical pesticides data...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2010 Biochemical pesticides... required to support registration of biochemical pesticides. Sections 158.2080 through 158.2084 identify the...

  1. 40 CFR 158.2010 - Biochemical pesticides data requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Biochemical pesticides data...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2010 Biochemical pesticides... required to support registration of biochemical pesticides. Sections 158.2080 through 158.2084 identify the...

  2. 40 CFR 158.2010 - Biochemical pesticides data requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Biochemical pesticides data...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2010 Biochemical pesticides... required to support registration of biochemical pesticides. Sections 158.2080 through 158.2084 identify the...

  3. 40 CFR 158.2000 - Biochemical pesticides definition and applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Biochemical pesticides definition and...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs (a...

  4. Biochemical Production of Ethanol from Corn Stover: 2007 State of Technology Model

    SciTech Connect

    Aden, Andy

    2008-05-01

    Since 2001, NREL has kept track of technical research progress in the biochemical process through what are known as “State of Technology” (SOT) assessments. The purpose of this report is to update the FY 2005 SOT model with the latest research results from the past two years.

  5. Research

    ERIC Educational Resources Information Center

    Mathematics Teaching, 1973

    1973-01-01

    Implications for teachers from Piagetian-oriented piagetian-oriented research on problem solving reported in an article by Eleanor Duckworth are presented. Edward de Bono's Children Solve Problems,'' a collection of examples, is also discussed. (MS)

  6. eQuilibrator--the biochemical thermodynamics calculator.

    PubMed

    Flamholz, Avi; Noor, Elad; Bar-Even, Arren; Milo, Ron

    2012-01-01

    The laws of thermodynamics constrain the action of biochemical systems. However, thermodynamic data on biochemical compounds can be difficult to find and is cumbersome to perform calculations with manually. Even simple thermodynamic questions like 'how much Gibbs energy is released by ATP hydrolysis at pH 5?' are complicated excessively by the search for accurate data. To address this problem, eQuilibrator couples a comprehensive and accurate database of thermodynamic properties of biochemical compounds and reactions with a simple and powerful online search and calculation interface. The web interface to eQuilibrator (http://equilibrator.weizmann.ac.il) enables easy calculation of Gibbs energies of compounds and reactions given arbitrary pH, ionic strength and metabolite concentrations. The eQuilibrator code is open-source and all thermodynamic source data are freely downloadable in standard formats. Here we describe the database characteristics and implementation and demonstrate its use.

  7. Biochemical Removal of HAP Precursors From Coal

    SciTech Connect

    Olson, G.; Tucker, L.; Richards, J.

    1997-07-01

    This project addresses DOE`s interest in advanced concepts for controlling emissions of air toxics from coal-fired utility boilers. We are determining the feasibility of developing a biochemical process for the precombustion removal of substantial percentages of 13 inorganic hazardous air pollutant (HAP) precursors from coal. These HAP precursors are Sb, As, Be, Cd, Cr, Cl, Co, F, Pb, Hg, Mn, Ni, and Se. Although rapid physical coal cleaning is done routinely in preparation plants, biochemical processes for removal of HAP precursors from coal potentially offer advantages of deeper cleaning, more specificity, and less coal loss. Compared to chemical processes for coal cleaning, biochemical processes potentially offer lower costs and milder process conditions. Pyrite oxidizing bacteria, most notably Thiobacillusferrooxidans, are being evaluated in this project for their ability to remove HAP precursors from U.S. coals.

  8. Simulation of cellular biochemical system kinetics.

    PubMed

    Beard, Daniel A

    2011-01-01

    The goal of realistically and reliably simulating the biochemical processes underlying cellular function is achievable through a systematic approach that makes use of the broadest possible amount of in vitro and in vivo data, and is consistent with all applicable physical chemical theories. Progress will be facilitated by establishing: (1) a concrete self-consistent theoretical foundation for systems simulation; (2) extensive and accurate databases of thermodynamic properties of biochemical reactions; (3) parameterized and validated models of enzyme and transporter catalytic mechanisms that are consistent with physical chemical theoretical foundation; and (4) software tools for integrating all these concepts, data, and models into a cohesive representation of cellular biochemical systems. Ongoing initiatives are laying the groundwork for the broad-based community cooperation that will be necessary to pursue these elements of a strategic infrastructure for systems simulation on a large scale. Copyright © 2010 John Wiley & Sons, Inc.

  9. eQuilibrator—the biochemical thermodynamics calculator

    PubMed Central

    Flamholz, Avi; Noor, Elad; Bar-Even, Arren; Milo, Ron

    2012-01-01

    The laws of thermodynamics constrain the action of biochemical systems. However, thermodynamic data on biochemical compounds can be difficult to find and is cumbersome to perform calculations with manually. Even simple thermodynamic questions like ‘how much Gibbs energy is released by ATP hydrolysis at pH 5?’ are complicated excessively by the search for accurate data. To address this problem, eQuilibrator couples a comprehensive and accurate database of thermodynamic properties of biochemical compounds and reactions with a simple and powerful online search and calculation interface. The web interface to eQuilibrator (http://equilibrator.weizmann.ac.il) enables easy calculation of Gibbs energies of compounds and reactions given arbitrary pH, ionic strength and metabolite concentrations. The eQuilibrator code is open-source and all thermodynamic source data are freely downloadable in standard formats. Here we describe the database characteristics and implementation and demonstrate its use. PMID:22064852

  10. Biochemical characteristics among Mycobacterium bovis BCG substrains.

    PubMed

    Hayashi, Daisuke; Takii, Takemasa; Mukai, Tetsu; Makino, Masahiko; Yasuda, Emi; Horita, Yasuhiro; Yamamoto, Ryuji; Fujiwara, Akiko; Kanai, Keita; Kondo, Maki; Kawarazaki, Aya; Yano, Ikuya; Yamamoto, Saburo; Onozaki, Kikuo

    2010-05-01

    In order to evaluate the biochemical characteristics of 14 substrains of Mycobacterium bovis bacillus Calmette Guérin (BCG) - Russia, Moreau, Japan, Sweden, Birkhaug, Danish, Glaxo, Mexico, Tice, Connaught, Montreal, Phipps, Australia and Pasteur - we performed eight different biochemical tests, including those for nitrate reduction, catalase, niacin accumulation, urease, Tween 80 hydrolysis, pyrazinamidase, p-amino salicylate degradation and resistance to thiophene 2-carboxylic acid hydrazide. Catalase activities of the substrains were all low. Data for nitrate reduction, niacin accumulation, Tween 80 hydrolysis, susceptibility to hydrogen peroxide and nitrate, and optimal pH for growth were all variable among these substrains. These findings suggest that the heterogeneities of biochemical characteristics are relevant to the differences in resistance of BCG substrains to environmental stress. The study also contributes to the re-evaluation of BCG substrains for use as vaccines.

  11. Parameter Inference for Biochemical Systems that Undergo a Hopf Bifurcation

    PubMed Central

    Kirk, Paul D. W.; Toni, Tina; Stumpf, Michael P. H.

    2008-01-01

    The increasingly widespread use of parametric mathematical models to describe biological systems means that the ability to infer model parameters is of great importance. In this study, we consider parameter inferability in nonlinear ordinary differential equation models that undergo a bifurcation, focusing on a simple but generic biochemical reaction model. We systematically investigate the shape of the likelihood function for the model's parameters, analyzing the changes that occur as the model undergoes a Hopf bifurcation. We demonstrate that there exists an intrinsic link between inference and the parameters' impact on the modeled system's dynamical stability, which we hope will motivate further research in this area. PMID:18456830

  12. Remote sensing of forest canopy and leaf biochemical contents

    NASA Technical Reports Server (NTRS)

    Peterson, David L.; Matson, Pamela A.; Card, Don H.; Aber, John D.; Wessman, Carol; Swanberg, Nancy; Spanner, Michael

    1988-01-01

    Recent research on the remote sensing of forest leaf and canopy biochemical contents suggests that the shortwave IR region contains this information; laboratory analyses of dry ground leaves have yielded reliable predictive relationships between both leaf nitrogen and lignin with near-IR spectra. Attention is given to the application of these laboratory techniques to a limited set of spectra from fresh, whole leaves of conifer species. The analysis of Airborne Imaging Spectrometer data reveals that total water content variations in deciduous forest canopies appear as overall shifts in the brightness of raw spectra.

  13. Remote sensing of forest canopy and leaf biochemical contents

    NASA Technical Reports Server (NTRS)

    Peterson, David L.; Matson, Pamela A.; Card, Don H.; Aber, John D.; Wessman, Carol; Swanberg, Nancy; Spanner, Michael

    1988-01-01

    Recent research on the remote sensing of forest leaf and canopy biochemical contents suggests that the shortwave IR region contains this information; laboratory analyses of dry ground leaves have yielded reliable predictive relationships between both leaf nitrogen and lignin with near-IR spectra. Attention is given to the application of these laboratory techniques to a limited set of spectra from fresh, whole leaves of conifer species. The analysis of Airborne Imaging Spectrometer data reveals that total water content variations in deciduous forest canopies appear as overall shifts in the brightness of raw spectra.

  14. [Experimental testing of micro biochemical analytical system].

    PubMed

    Chen, Gang; Wen, Zhi-yu; Wen, Zhong-quan; Xu, Yi; Li, Xia; Jiang, Zi-ping

    2005-03-01

    A micro biochemical analytical system based on a micro fiber spectrometer is introduced. Experiment was carried out to calibrate and test the analysis system. In the experiment, the absorption spectra of Fe2+ -ferroin solution bodies with different concentrations were obtained. The working curve shows a fine linearity of the analysis system. The authors also compared the experimental results obtained from 722-spectrometer and those from our analysis system. It was shown that their system can meet the requirement of practical use. This system also has many advantages, such as real-time whole spectrum analyzing and small volume, and is an ideal instrument for biochemical analysis.

  15. Simulation of Biochemical Pathway Adaptability Using Evolutionary Algorithms

    SciTech Connect

    Bosl, W J

    2005-01-26

    -driven experimentation. This LDRD will focus on developing prototype software for the evolutionary computation and demonstrating its efficacy on a well-known biochemical pathway in yeast. Expected outcomes from this LDRD project included a demonstration of computational modeling of evolvability in a biochemical pathway, an important collaboration with the Systems Biology department at Harvard University, several proposals to secure external long-term funding from one or more sources and the nucleus of a new, focused research effort at LLNL in computational genomics, focused principally on Genomes to Life goals. All of these goals were achieved.

  16. Toxins–Useful Biochemical Tools for Leukocyte Research

    PubMed Central

    Cubillos, Susana; Norgauer, Johannes; Lehmann, Katja

    2010-01-01

    Leukocytes are a heterogeneous group of cells that display differences in anatomic localization, cell surface phenotype, and function. The different subtypes include e.g., granulocytes, monocytes, dendritic cells, T cells, B cells and NK cells. These different cell types represent the cellular component of innate and adaptive immunity. Using certain toxins such as pertussis toxin, cholera toxin or clostridium difficile toxin, the regulatory functions of Gαi, Gαs and small GTPases of the Rho family in leukocytes have been reported. A summary of these reports is discussed in this review. PMID:22069594

  17. Biochemical Applications in the Analytical Chemistry Lab

    ERIC Educational Resources Information Center

    Strong, Cynthia; Ruttencutter, Jeffrey

    2004-01-01

    An HPLC and a UV-visible spectrophotometer are identified as instruments that helps to incorporate more biologically-relevant experiments into the course, in order to increase the students understanding of selected biochemistry topics and enhances their ability to apply an analytical approach to biochemical problems. The experiment teaches…

  18. Biochemical Applications in the Analytical Chemistry Lab

    ERIC Educational Resources Information Center

    Strong, Cynthia; Ruttencutter, Jeffrey

    2004-01-01

    An HPLC and a UV-visible spectrophotometer are identified as instruments that helps to incorporate more biologically-relevant experiments into the course, in order to increase the students understanding of selected biochemistry topics and enhances their ability to apply an analytical approach to biochemical problems. The experiment teaches…

  19. 2009 Biochemical Conversion Platform Review Report

    SciTech Connect

    Ferrell, John

    2009-12-01

    This document summarizes the recommendations and evaluations provided by an independent external panel of experts at the U.S. Department of Energy Biomass Program’s Biochemical Conversion platform review meeting, held on April 14-16, 2009, at the Sheraton Denver Downtown, Denver, Colorado.

  20. A Course in Biochemical Engineering Fundamentals (Revisited).

    ERIC Educational Resources Information Center

    Bailey, J. E.; Ollis, D. F.

    1985-01-01

    Provides: (1) a glossary of terms used in biochemical engineering; (2) a list of key developments in the field; and (3) emphases placed in 15 topic areas in a course restructured on the basis of these developments. Topic areas include enzyme kinetics/applications, genetics and microbial control, transport phenomena, and others. (JN)

  1. Survey of Biochemical Education in Japanese Universities.

    ERIC Educational Resources Information Center

    Kagawa, Yasuo

    1995-01-01

    Reports findings of questionnaires sent to faculty in charge of biochemical education in medical schools and other programs from dentistry to agriculture. Total class hours have declined since 1984. New trends include bioethics and computer-assisted learning. Tables show trends in lecture hours, lecture content, laboratory hours, core subject…

  2. Metabonomics and medicine: the Biochemical Oracle.

    PubMed

    Mitchell, Steve; Holmes, Elaine; Carmichael, Paul

    2002-10-01

    Occasionally, a new idea emerges that has the potential to revolutionize an entire field of scientific endeavour. It is now within our grasp to be able to detect subtle perturbations within the phenomenally complex biochemical matrix of living organisms. The discipline of metabonomics promises an all-encompassing approach to understanding total, yet fundamental, changes occurring in disease processes, drug toxicity and cell function.

  3. Biochemical Approaches to Improved Nitrogen Fixation

    USDA-ARS?s Scientific Manuscript database

    Improving symbiotic nitrogen fixation by legumes has emerged again as an important topic on the world scene due to the energy crisis and lack of access to nitrogen fertilizer in developing countries. We have taken a biochemical genomics approach to improving symbiotic nitrogen fixation in legumes. L...

  4. Survey of Biochemical Education in Japanese Universities.

    ERIC Educational Resources Information Center

    Kagawa, Yasuo

    1995-01-01

    Reports findings of questionnaires sent to faculty in charge of biochemical education in medical schools and other programs from dentistry to agriculture. Total class hours have declined since 1984. New trends include bioethics and computer-assisted learning. Tables show trends in lecture hours, lecture content, laboratory hours, core subject…

  5. Biochemical Thermodynamics under near Physiological Conditions

    ERIC Educational Resources Information Center

    Mendez, Eduardo

    2008-01-01

    The recommendations for nomenclature and tables in Biochemical Thermodynamics approved by IUBMB and IUPAC in 1994 can be easily introduced after the chemical thermodynamic formalism. Substitution of the usual standard thermodynamic properties by the transformed ones in the thermodynamic equations, and the use of appropriate thermodynamic tables…

  6. Biochemical changes in the injured brain

    PubMed Central

    Sahu, Seelora; Nag, Deb Sanjay; Swain, Amlan; Samaddar, Devi Prasad

    2017-01-01

    Brain metabolism is an energy intensive phenomenon involving a wide spectrum of chemical intermediaries. Various injury states have a detrimental effect on the biochemical processes involved in the homeostatic and electrophysiological properties of the brain. The biochemical markers of brain injury are a recent addition in the armamentarium of neuro-clinicians and are being increasingly used in the routine management of neuro-pathological entities such as traumatic brain injury, stroke, subarachnoid haemorrhage and intracranial space occupying lesions. These markers are increasingly being used in assessing severity as well as in predicting the prognostic course of neuro-pathological lesions. S-100 protein, neuron specific enolase, creatinine phosphokinase isoenzyme BB and myelin basic protein are some of the biochemical markers which have been proven to have prognostic and clinical value in the brain injury. While S-100, glial fibrillary acidic protein and ubiquitin C terminal hydrolase are early biomarkers of neuronal injury and have the potential to aid in clinical decision-making in the initial management of patients presenting with an acute neuronal crisis, the other biomarkers are of value in predicting long-term complications and prognosis in such patients. In recent times cerebral microdialysis has established itself as a novel way of monitoring brain tissue biochemical metabolites such as glucose, lactate, pyruvate, glutamate and glycerol while small non-coding RNAs have presented themselves as potential markers of brain injury for future. PMID:28289516

  7. Biochemical Thermodynamics under near Physiological Conditions

    ERIC Educational Resources Information Center

    Mendez, Eduardo

    2008-01-01

    The recommendations for nomenclature and tables in Biochemical Thermodynamics approved by IUBMB and IUPAC in 1994 can be easily introduced after the chemical thermodynamic formalism. Substitution of the usual standard thermodynamic properties by the transformed ones in the thermodynamic equations, and the use of appropriate thermodynamic tables…

  8. Biochemical changes in the injured brain.

    PubMed

    Sahu, Seelora; Nag, Deb Sanjay; Swain, Amlan; Samaddar, Devi Prasad

    2017-02-26

    Brain metabolism is an energy intensive phenomenon involving a wide spectrum of chemical intermediaries. Various injury states have a detrimental effect on the biochemical processes involved in the homeostatic and electrophysiological properties of the brain. The biochemical markers of brain injury are a recent addition in the armamentarium of neuro-clinicians and are being increasingly used in the routine management of neuro-pathological entities such as traumatic brain injury, stroke, subarachnoid haemorrhage and intracranial space occupying lesions. These markers are increasingly being used in assessing severity as well as in predicting the prognostic course of neuro-pathological lesions. S-100 protein, neuron specific enolase, creatinine phosphokinase isoenzyme BB and myelin basic protein are some of the biochemical markers which have been proven to have prognostic and clinical value in the brain injury. While S-100, glial fibrillary acidic protein and ubiquitin C terminal hydrolase are early biomarkers of neuronal injury and have the potential to aid in clinical decision-making in the initial management of patients presenting with an acute neuronal crisis, the other biomarkers are of value in predicting long-term complications and prognosis in such patients. In recent times cerebral microdialysis has established itself as a novel way of monitoring brain tissue biochemical metabolites such as glucose, lactate, pyruvate, glutamate and glycerol while small non-coding RNAs have presented themselves as potential markers of brain injury for future.

  9. Biochemical reactions of ozone in plants

    Treesearch

    J. Brian Mudd

    1998-01-01

    Plants react biochemically to ozone in three phases: with constitutive chemicals in the apoplastic fluid and cell membranes; by forming messenger molecules by the affected constitutive materials (ethylene); and by responding to the messenger molecules with pathogenic RNAs and proteins. For instance, plant reactions with ozone result in constitutive molecules such as...

  10. Characterizing autism spectrum disorders by key biochemical pathways

    PubMed Central

    Subramanian, Megha; Timmerman, Christina K.; Schwartz, Joshua L.; Pham, Daniel L.; Meffert, Mollie K.

    2015-01-01

    The genetic and phenotypic heterogeneity of autism spectrum disorders (ASD) presents a substantial challenge for diagnosis, classification, research, and treatment. Investigations into the underlying molecular etiology of ASD have often yielded mixed and at times opposing findings. Defining the molecular and biochemical underpinnings of heterogeneity in ASD is crucial to our understanding of the pathophysiological development of the disorder, and has the potential to assist in diagnosis and the rational design of clinical trials. In this review, we propose that genetically diverse forms of ASD may be usefully parsed into entities resulting from converse patterns of growth regulation at the molecular level, which lead to the correlates of general synaptic and neural overgrowth or undergrowth. Abnormal brain growth during development is a characteristic feature that has been observed both in children with autism and in mouse models of autism. We review evidence from syndromic and non-syndromic ASD to suggest that entities currently classified as autism may fundamentally differ by underlying pro- or anti-growth abnormalities in key biochemical pathways, giving rise to either excessive or reduced synaptic connectivity in affected brain regions. We posit that this classification strategy has the potential not only to aid research efforts, but also to ultimately facilitate early diagnosis and direct appropriate therapeutic interventions. PMID:26483618

  11. Characterizing autism spectrum disorders by key biochemical pathways.

    PubMed

    Subramanian, Megha; Timmerman, Christina K; Schwartz, Joshua L; Pham, Daniel L; Meffert, Mollie K

    2015-01-01

    The genetic and phenotypic heterogeneity of autism spectrum disorders (ASD) presents a substantial challenge for diagnosis, classification, research, and treatment. Investigations into the underlying molecular etiology of ASD have often yielded mixed and at times opposing findings. Defining the molecular and biochemical underpinnings of heterogeneity in ASD is crucial to our understanding of the pathophysiological development of the disorder, and has the potential to assist in diagnosis and the rational design of clinical trials. In this review, we propose that genetically diverse forms of ASD may be usefully parsed into entities resulting from converse patterns of growth regulation at the molecular level, which lead to the correlates of general synaptic and neural overgrowth or undergrowth. Abnormal brain growth during development is a characteristic feature that has been observed both in children with autism and in mouse models of autism. We review evidence from syndromic and non-syndromic ASD to suggest that entities currently classified as autism may fundamentally differ by underlying pro- or anti-growth abnormalities in key biochemical pathways, giving rise to either excessive or reduced synaptic connectivity in affected brain regions. We posit that this classification strategy has the potential not only to aid research efforts, but also to ultimately facilitate early diagnosis and direct appropriate therapeutic interventions.

  12. Kombucha tea fermentation: Microbial and biochemical dynamics.

    PubMed

    Chakravorty, Somnath; Bhattacharya, Semantee; Chatzinotas, Antonis; Chakraborty, Writachit; Bhattacharya, Debanjana; Gachhui, Ratan

    2016-03-02

    Kombucha tea, a non-alcoholic beverage, is acquiring significant interest due to its claimed beneficial properties. The microbial community of Kombucha tea consists of bacteria and yeast which thrive in two mutually non-exclusive compartments: the soup or the beverage and the biofilm floating on it. The microbial community and the biochemical properties of the beverage have so far mostly been described in separate studies. This, however, may prevent understanding the causal links between the microbial communities and the beneficial properties of Kombucha tea. Moreover, an extensive study into the microbial and biochemical dynamics has also been missing. In this study, we thus explored the structure and dynamics of the microbial community along with the biochemical properties of Kombucha tea at different time points up to 21 days of fermentation. We hypothesized that several biochemical properties will change during the course of fermentation along with the shifts in the yeast and bacterial communities. The yeast community of the biofilm did not show much variation over time and was dominated by Candida sp. (73.5-83%). The soup however, showed a significant shift in dominance from Candida sp. to Lachancea sp. on the 7th day of fermentation. This is the first report showing Candida as the most dominating yeast genus during Kombucha fermentation. Komagateibacter was identified as the single largest bacterial genus present in both the biofilm and the soup (~50%). The bacterial diversity was higher in the soup than in the biofilm with a peak on the seventh day of fermentation. The biochemical properties changed with the progression of the fermentation, i.e., beneficial properties of the beverage such as the radical scavenging ability increased significantly with a maximum increase at day 7. We further observed a significantly higher D-saccharic acid-1,4-lactone content and caffeine degradation property compared to previously described Kombucha tea fermentations. Our

  13. A general method for modeling biochemical and biomedical response

    NASA Astrophysics Data System (ADS)

    Ortiz, Roberto; Lerd Ng, Jia; Hughes, Tyler; Abou Ghantous, Michel; Bouhali, Othmane; Arredouani, Abdelilah; Allen, Roland

    2012-10-01

    The impressive achievements of biomedical science have come mostly from experimental research with human subjects, animal models, and sophisticated laboratory techniques. Additionally, theoretical chemistry has been a major aid in designing new drugs. Here we introduce a method which is similar to others already well known in theoretical systems biology, but which specifically addresses biochemical changes as the human body responds to medical interventions. It is common in systems biology to use first-order differential equations to model the time evolution of various chemical concentrations, and we as physicists can make a significant impact through designing realistic models and then solving the resulting equations. Biomedical research is rapidly advancing, and the technique presented in this talk can be applied in arbitrarily large models containing tens, hundreds, or even thousands of interacting species, to determine what beneficial effects and side effects may result from pharmaceuticals or other medical interventions.

  14. Biochemical Genetic Pathways that Modulate Aging in Multiple Species

    PubMed Central

    Bitto, Alessandro; Wang, Adrienne M.; Bennett, Christopher F.; Kaeberlein, Matt

    2016-01-01

    The mechanisms underlying biological aging have been extensively studied in the past 20 years with the avail of mainly four model organisms: the budding yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, the fruitfly Drosophila melanogaster, and the domestic mouse Mus musculus. Extensive research in these four model organisms has identified a few conserved genetic pathways that affect longevity as well as metabolism and development. Here, we review how the mechanistic target of rapamycin (mTOR), sirtuins, adenosine monophosphate-activated protein kinase (AMPK), growth hormone/insulin-like growth factor 1 (IGF-1), and mitochondrial stress-signaling pathways influence aging and life span in the aforementioned models and their possible implications for delaying aging in humans. We also draw some connections between these biochemical pathways and comment on what new developments aging research will likely bring in the near future. PMID:26525455

  15. Self-organizing ontology of biochemically relevant small molecules

    PubMed Central

    2012-01-01

    Background The advent of high-throughput experimentation in biochemistry has led to the generation of vast amounts of chemical data, necessitating the development of novel analysis, characterization, and cataloguing techniques and tools. Recently, a movement to publically release such data has advanced biochemical structure-activity relationship research, while providing new challenges, the biggest being the curation, annotation, and classification of this information to facilitate useful biochemical pattern analysis. Unfortunately, the human resources currently employed by the organizations supporting these efforts (e.g. ChEBI) are expanding linearly, while new useful scientific information is being released in a seemingly exponential fashion. Compounding this, currently existing chemical classification and annotation systems are not amenable to automated classification, formal and transparent chemical class definition axiomatization, facile class redefinition, or novel class integration, thus further limiting chemical ontology growth by necessitating human involvement in curation. Clearly, there is a need for the automation of this process, especially for novel chemical entities of biological interest. Results To address this, we present a formal framework based on Semantic Web technologies for the automatic design of chemical ontology which can be used for automated classification of novel entities. We demonstrate the automatic self-assembly of a structure-based chemical ontology based on 60 MeSH and 40 ChEBI chemical classes. This ontology is then used to classify 200 compounds with an accuracy of 92.7%. We extend these structure-based classes with molecular feature information and demonstrate the utility of our framework for classification of functionally relevant chemicals. Finally, we discuss an iterative approach that we envision for future biochemical ontology development. Conclusions We conclude that the proposed methodology can ease the burden of

  16. Numerical Simulation of Bubbly Flows in an Aeration Tank with Biochemical Reactions

    NASA Astrophysics Data System (ADS)

    Noor Ul Huda, Khateeb; Shimizu, Kazuya; Gong, Xiaobo; Takagi, Shu

    2016-11-01

    For bubbly flow with biochemical reactions, all the analyses including overall fluid flow, bubble motion, bubble dissolution at local level and bacterial reactions/consumption of substrates are important. The developed system is provided by mixed Eulerian-Lagrangian formulation in which liquid media is represented in Eulerian system and bubbles are tracked individually. Murai and Matsumoto developed a model to track bubbles to predict plume structure in finely dispersed domain. Gong et al. developed the model further to include mass transfer, gas dissolution and mixing phenomenon entrained in this model. In this research we are using the model to include simulation of bacterial biochemical reactions for the purification of water and make it resemble as the wastewater purification tank. The gas bubble dissolution and mass transfer from gas to liquid phase is linked with biochemical reactions for an overall comprehensive study. The main area associated with this research is to incorporate all biochemical reactions in this bubbly flow based on situation of water and demand. In this particular study, various kinds of biomass and substrates are considered. A detailed model for biological wastewater purification involving reactions using bacteria's is developed and primary validation has been carried out based on experimental study. Finally, we tried to achieve physical optimization for this biochemical reactions.

  17. Biochemical and immunohistochemical characterization of Mimosa annexin.

    PubMed

    Hoshino, Daisuke; Hayashi, Asami; Temmei, Yusuke; Kanzawa, Nobuyuki; Tsuchiya, Takahide

    2004-09-01

    To characterize the biochemical properties of plant annexin, we isolated annexin from Mimosa pudica L. and analyzed the biochemical properties conserved between Mimosa annexin and animal annexins, e.g. the ability to bind phospholipid and F-actin in the presence of calcium. We show that Mimosa annexin is distributed in a wide variety of tissues. Immunoblot analysis also revealed that the amount of annexin is developmentally regulated. To identify novel functions of Mimosa annexin, we examined the pattern of distribution and the regulation of its expression in the pulvinus. The amount of annexin in the pulvinus increased at night and was sensitive to abscisic acid; however, there was no detectable induction of annexin by cold or mechanical stimulus. Annexin distribution in the cell periphery during the daytime was changed to a cytoplasmic distribution at night, indicating that Mimosa annexin may contribute to the nyctinastic movement in the pulvinus.

  18. Thermodynamics of biochemical networks and duality theorems.

    PubMed

    De Martino, Daniele

    2013-05-01

    One interesting yet difficult computational issue has recently been posed in biophysics in regard to the implementation of thermodynamic constraints to complex networks. Biochemical networks of enzymes inside cells are among the most efficient, robust, differentiated, and flexible free-energy transducers in nature. How is the second law of thermodynamics encoded for these complex networks? In this article it is demonstrated that for chemical reaction networks in the steady state the exclusion (presence) of closed reaction cycles makes possible (impossible) the definition of a chemical potential vector. Interestingly, this statement is encoded in one of the key results in combinatorial optimization, i.e., the Gordan theorem of the alternatives. From a computational viewpoint, the theorem reveals that calculating a reaction's free energy and identifying infeasible loops in flux states are dual problems whose solutions are mutually exclusive, and this opens the way for efficient and scalable methods to perform the energy balance analysis of large-scale biochemical networks.

  19. Construction and analysis of biochemical networks

    NASA Astrophysics Data System (ADS)

    Binns, Michael; Theodoropoulos, Constantinos

    2012-09-01

    Bioprocesses are being implemented for a range of different applications including the production of fuels, chemicals and drugs. Hence, it is becoming increasingly important to understand and model how they function and how they can be modified or designed to give the optimal performance. Here we discuss the construction and analysis of biochemical networks which are the first logical steps towards this goal. The construction of a reaction network is possible through reconstruction: extracting information from literature and from databases. This can be supplemented by reaction prediction methods which can identify steps which are missing from the current knowledge base. Analysis of biochemical systems generally requires some experimental input but can be used to identify important reactions and targets for enhancing the performance of the organism involved. Metabolic flux, pathway and metabolic control analysis can be used to determine the limits, capabilities and potential targets for enhancement respectively.

  20. Molecular and biochemical mechanisms of preterm labour.

    PubMed

    Mohan, Aarthi R; Loudon, Jenifer A; Bennett, Phillip R

    2004-12-01

    Parturition involves the synchronization of myometrial activity and structural changes of the cervix, leading to regular co-ordinated uterine contractions and cervical dilatation and effacement. The biochemical events involved in parturition resemble an inflammatory reaction, with growing evidence pointing to a crucial role for pro-inflammatory cytokines and prostaglandins in labour. There is accumulating evidence that there are common mediators involved in the regulation of 'labour-associated proteins', and that, in each case, an increase or decrease in gene expression mediates changes in their concentration. It is possible, therefore, that targeting these common mediators may represent newer strategies for the prevention of preterm labour. Our aim is to review the mechanical and biochemical mechanisms that may be involved in the processes of term and preterm labour. Specifically, we will consider the regulation of some of the 'labour-associated proteins', chemotactic cytokines, prostaglandins and enzymes of the prostaglandin biosynthetic pathway and the oxytocin receptor.

  1. Thermodynamics of Computational Copying in Biochemical Systems

    NASA Astrophysics Data System (ADS)

    Ouldridge, Thomas E.; Govern, Christopher C.; ten Wolde, Pieter Rein

    2017-04-01

    Living cells use readout molecules to record the state of receptor proteins, similar to measurements or copies in typical computational devices. But is this analogy rigorous? Can cells be optimally efficient, and if not, why? We show that, as in computation, a canonical biochemical readout network generates correlations; extracting no work from these correlations sets a lower bound on dissipation. For general input, the biochemical network cannot reach this bound, even with arbitrarily slow reactions or weak thermodynamic driving. It faces an accuracy-dissipation trade-off that is qualitatively distinct from and worse than implied by the bound, and more complex steady-state copy processes cannot perform better. Nonetheless, the cost remains close to the thermodynamic bound unless accuracy is extremely high. Additionally, we show that biomolecular reactions could be used in thermodynamically optimal devices under exogenous manipulation of chemical fuels, suggesting an experimental system for testing computational thermodynamics.

  2. Advances in Biochemical Indices of Zooplankton Production.

    PubMed

    Yebra, L; Kobari, T; Sastri, A R; Gusmão, F; Hernández-León, S

    Several new approaches for measuring zooplankton growth and production rates have been developed since the publication of the ICES (International Council for the Exploration of the Sea) Zooplankton Methodology Manual (Harris et al., 2000). In this review, we summarize the advances in biochemical methods made in recent years. Our approach explores the rationale behind each method, the design of calibration experiments, the advantages and limitations of each method and their suitability as proxies for in situ rates of zooplankton community growth and production. We also provide detailed protocols for the existing methods and information relevant to scientists wanting to apply, calibrate or develop these biochemical indices for zooplankton production. © 2017 Elsevier Ltd. All rights reserved.

  3. Structural and biochemical characterization of DSL ribozyme.

    PubMed

    Horie, Souta; Ikawa, Yoshiya; Inoue, Tan

    2006-01-06

    We recently reported on the molecular design and synthesis of a new RNA ligase ribozyme (DSL), whose active site was selected from a sequence library consisting of 30 random nucleotides set on a defined 3D structure of a designed RNA scaffold. In this study, we report on the structural and biochemical analyses of DSL. Structural analysis indicates that the active site, which consists of the selected sequence, attaches to the folded scaffold as designed. To see whether DSL resembles known ribozymes, a biochemical assay was performed. Metal-dependent kinetic studies suggest that the ligase requires Mg2+ ions. The replacement of Mg2+ with Co(NH3)6(3+) prohibits the reaction, indicating that DSL requires innersphere coordination of Mg2+ for a ligation reaction. The results show that DSL has requirements similar to those of previously reported catalytic RNAs.

  4. Pitfalls in the interpretation of common biochemical tests

    PubMed Central

    Ayling, R.

    2000-01-01

    This review considers some of the more common problems in the interpretation of the results of biochemical tests and, where possible, highlights ways in which errors can be identified or avoided.


Keywords: biochemical tests PMID:10684320

  5. Biochemical correlates of neurosensory changes in weightlessness

    NASA Technical Reports Server (NTRS)

    Leach, Carolyn S.; Reschke, Millard F.

    1989-01-01

    The possible existence of a relationship between space motion sickness and chemical and biochemical variables measured in body fluids is studied. Clinical chemistry and endocrine measurements from blood and urine samples taken before and after Space Shuttle flights were analyzed along with the occurrence of SMS during flight and provocative testing before flight. Significant positive correlations were observed with serum chloride and significant negative correlations with serum phosphate, serum uric acid, and plasma thyroid stimulating hormone.

  6. Biochemical correlates of neurosensory changes in weightlessness

    NASA Technical Reports Server (NTRS)

    Leach, Carolyn S.; Reschke, Millard F.

    1989-01-01

    The possible existence of a relationship between space motion sickness and chemical and biochemical variables measured in body fluids is studied. Clinical chemistry and endocrine measurements from blood and urine samples taken before and after Space Shuttle flights were analyzed along with the occurrence of SMS during flight and provocative testing before flight. Significant positive correlations were observed with serum chloride and significant negative correlations with serum phosphate, serum uric acid, and plasma thyroid stimulating hormone.

  7. Biochemical and pharmacologic comparison of thrombolytic agents.

    PubMed

    Stringer, K A

    1996-01-01

    The number of thrombolytic drugs for the management of acute myocardial infarction is rapidly expanding. New agents, some of which are biochemically modified versions of currently available thrombolytics, will soon arrive in the marketplace. The pharmacologic differences of the new drugs are the basis for clinical differences such as enhanced clot lysis and prolonged elimination half-life. Ultimately, these features may result in improved infarct artery patency and patient survival.

  8. Electronic modulation of biochemical signal generation

    NASA Astrophysics Data System (ADS)

    Gordonov, Tanya; Kim, Eunkyoung; Cheng, Yi; Ben-Yoav, Hadar; Ghodssi, Reza; Rubloff, Gary; Yin, Jun-Jie; Payne, Gregory F.; Bentley, William E.

    2014-08-01

    Microelectronic devices that contain biological components are typically used to interrogate biology rather than control biological function. Patterned assemblies of proteins and cells have, however, been used for in vitro metabolic engineering, where coordinated biochemical pathways allow cell metabolism to be characterized and potentially controlled on a chip. Such devices form part of technologies that attempt to recreate animal and human physiological functions on a chip and could be used to revolutionize drug development. These ambitious goals will, however, require new biofabrication methodologies that help connect microelectronics and biological systems and yield new approaches to device assembly and communication. Here, we report the electrically mediated assembly, interrogation and control of a multi-domain fusion protein that produces a bacterial signalling molecule. The biological system can be electrically tuned using a natural redox molecule, and its biochemical response is shown to provide the signalling cues to drive bacterial population behaviour. We show that the biochemical output of the system correlates with the electrical input charge, which suggests that electrical inputs could be used to control complex on-chip biological processes.

  9. Controllability of non-linear biochemical systems.

    PubMed

    Ervadi-Radhakrishnan, Anandhi; Voit, Eberhard O

    2005-07-01

    Mathematical methods of biochemical pathway analysis are rapidly maturing to a point where it is possible to provide objective rationale for the natural design of metabolic systems and where it is becoming feasible to manipulate these systems based on model predictions, for instance, with the goal of optimizing the yield of a desired microbial product. So far, theory-based metabolic optimization techniques have mostly been applied to steady-state conditions or the minimization of transition time, using either linear stoichiometric models or fully kinetic models within biochemical systems theory (BST). This article addresses the related problem of controllability, where the task is to steer a non-linear biochemical system, within a given time period, from an initial state to some target state, which may or may not be a steady state. For this purpose, BST models in S-system form are transformed into affine non-linear control systems, which are subjected to an exact feedback linearization that permits controllability through independent variables. The method is exemplified with a small glycolytic-glycogenolytic pathway that had been analyzed previously by several other authors in different contexts.

  10. Stoichiometric network theory for nonequilibrium biochemical systems.

    PubMed

    Qian, Hong; Beard, Daniel A; Liang, Shou-dan

    2003-02-01

    We introduce the basic concepts and develop a theory for nonequilibrium steady-state biochemical systems applicable to analyzing large-scale complex isothermal reaction networks. In terms of the stoichiometric matrix, we demonstrate both Kirchhoff's flux law sigma(l)J(l)=0 over a biochemical species, and potential law sigma(l) mu(l)=0 over a reaction loop. They reflect mass and energy conservation, respectively. For each reaction, its steady-state flux J can be decomposed into forward and backward one-way fluxes J = J+ - J-, with chemical potential difference deltamu = RT ln(J-/J+). The product -Jdeltamu gives the isothermal heat dissipation rate, which is necessarily non-negative according to the second law of thermodynamics. The stoichiometric network theory (SNT) embodies all of the relevant fundamental physics. Knowing J and deltamu of a biochemical reaction, a conductance can be computed which directly reflects the level of gene expression for the particular enzyme. For sufficiently small flux a linear relationship between J and deltamu can be established as the linear flux-force relation in irreversible thermodynamics, analogous to Ohm's law in electrical circuits.

  11. Biochemical assessment of acute myocardial ischaemia.

    PubMed Central

    Perez-Cárceles, M D; Osuna, E; Vieira, D N; Martínez, A; Luna, A

    1995-01-01

    AIMS--To evaluate the efficacy of biochemical parameters in different fluids in the diagnosis of myocardial infarction of different causes, analysed after death. METHODS--The myoglobin concentration and total creatine kinase (CK) and creatine kinase MB isoenzyme (CK-MB) activities were measured in serum, pericardial fluid, and vitreous humour from seven diagnostic groups of cadavers classified according to the severity of myocardial ischaemia and cause of death. Lactate dehydrogenase (LDH) and myosin were measured only in serum and pericardial fluid, and cathepsin D only in pericardial fluid. Routine haematoxylin and eosin and acridine orange staining were used for microscopy studies of heart tissue. RESULTS--In pericardial fluid there were substantial differences between the different groups with respect to CK, CK-MB, and LDH activities and myosin concentrations. The highest values were found in cases with morphological evidence of myocardial ischaemia. CONCLUSIONS--Biochemical parameters, which reach the pericardial fluid via passive diffusion and ultrafiltration due to a pressure gradient, were thus detectable in this fluid earlier than in serum in cases with myocardial ischaemia. These biochemical parameters may be of use for ruling out myocardial ischaemia in those controversial cases in which reliable morphological findings are lacking. PMID:7745110

  12. Hydrogel-based piezoresistive biochemical microsensors

    NASA Astrophysics Data System (ADS)

    Guenther, Margarita; Schulz, Volker; Gerlach, Gerald; Wallmersperger, Thomas; Solzbacher, Florian; Magda, Jules J.; Tathireddy, Prashant; Lin, Genyao; Orthner, Michael P.

    2010-04-01

    This work is motivated by a demand for inexpensive, robust and reliable biochemical sensors with high signal reproducibility and long-term-stable sensitivity, especially for medical applications. Micro-fabricated sensors can provide continuous monitoring and on-line control of analyte concentrations in ambient aqueous solutions. The piezoresistive biochemical sensor containing a special biocompatible polymer (hydrogel) with a sharp volume phase transition in the neutral physiological pH range near 7.4 can detect a specific analyte, for example glucose. Thereby the hydrogel-based biochemical sensors are useful for the diagnosis and monitoring of diabetes. The response of the glucosesensitive hydrogel was studied at different regimes of the glucose concentration change and of the solution supply. Sensor response time and accuracy with which a sensor can track gradual changes in glucose was estimated. Additionally, the influence of various recommended sterilization methods on the gel swelling properties and on the mechano-electrical transducer of the pH-sensors has been evaluated in order to choose the most optimal sterilization method for the implantable sensors. It has been shown that there is no negative effect of gamma irradiation with a dose of 25.7 kGy on the hydrogel sensitivity. In order to achieve an optimum between sensor signal amplitude and sensor response time, corresponding calibration and measurement procedures have been proposed and evaluated for the chemical sensors.

  13. Genetic and Biochemical Biomarkers in Canine Glaucoma.

    PubMed

    Graham, K L; McCowan, C; White, A

    2017-03-01

    In many health-related fields, there is great interest in the identification of biomarkers that distinguish diseased from healthy individuals. In addition to identifying the diseased state, biomarkers have potential use in predicting disease risk, monitoring disease progression, evaluating treatment efficacy, and informing pathogenesis. This review details the genetic and biochemical markers associated with canine primary glaucoma. While there are numerous molecular markers (biochemical and genetic) associated with glaucoma in dogs, there is no ideal biomarker that allows early diagnosis and/or identification of disease progression. Genetic mutations associated with canine glaucoma include those affecting ADAMTS10, ADAMTS17, Myocilin, Nebulin, COL1A2, RAB22A, and SRBD1. With the exception of Myocilin, there is very limited crossover in genetic biomarkers identified between human and canine glaucomas. Mutations associated with canine glaucoma vary between and within canine breeds, and gene discoveries therefore have limited overall effects as a screening tool in the general canine population. Biochemical markers of glaucoma include indicators of inflammation, oxidative stress, serum autoantibodies, matrix metalloproteinases, tumor necrosis factor-α, and transforming growth factor-β. These markers include those that indicate an adaptive or protective response, as well as those that reflect the damage arising from oxidative stress.

  14. The Use of Item Analysis for Improvement of Biochemical Teaching

    ERIC Educational Resources Information Center

    Nagata, Ryoichi

    2004-01-01

    Item analysis was used to find out which biochemical explanations need to be improved in biochemical teaching, not which items are to be discarded, improved, or reusable in biochemical examinations. The analysis revealed the basic facts of which less able students had more misunderstanding than able students. Identifying these basic facts helps…

  15. Biochemical Activities of 320 ToxCast Chemicals Evaluated Across 239 Functional Targets

    EPA Science Inventory

    EPA’s ToxCast research program is profiling chemical bioactivity in order to generate predictive signatures of toxicity. The present study evaluated 320 chemicals across 239 biochemical assays. ToxCast phase I chemicals include 309 unique structures, most of which are pesticide ...

  16. Biochemical Activities of 320 ToxCast Chemicals Evaluated Across 239 Functional Targets

    EPA Science Inventory

    EPA’s ToxCast research program is profiling chemical bioactivity in order to generate predictive signatures of toxicity. The present study evaluated 320 chemicals across 239 biochemical assays. ToxCast phase I chemicals include 309 unique structures, most of which are pesticide ...

  17. Biochemical and physical signal gradients in hydrogels to control stem cell behavior**

    PubMed Central

    Jeon, Oju; Alt, Daniel S.; Linderman, Stephen W.

    2013-01-01

    Three-dimensional (3D) gradients of biochemical and physical signals in macroscale, degradable hydrogels have been engineered that can regulate photoencapsulated human mesenchymal stem cell (hMSC) behavior. This simple, cytocompatible and versatile gradient system may be a valuable tool for researchers in biomaterials science to control stem cell fate in 3D and guide tissue regeneration. PMID:23983019

  18. [INVITED] Tilted fiber grating mechanical and biochemical sensors

    NASA Astrophysics Data System (ADS)

    Guo, Tuan; Liu, Fu; Guan, Bai-Ou; Albert, Jacques

    2016-04-01

    The tilted fiber Bragg grating (TFBG) is a new kind of fiber-optic sensor that possesses all the advantages of well-established Bragg grating technology in addition to being able to excite cladding modes resonantly. This device opens up a multitude of opportunities for single-point sensing in hard-to-reach spaces with very controllable cross-sensitivities, absolute and relative measurements of various parameters, and an extreme sensitivity to materials external to the fiber without requiring the fiber to be etched or tapered. Over the past five years, our research group has been developing multimodal fiber-optic sensors based on TFBG in various shapes and forms, always keeping the device itself simple to fabricate and compatible with low-cost manufacturing. This paper presents a brief review of the principle, fabrication, characterization, and implementation of TFBGs, followed by our progress in TFBG sensors for mechanical and biochemical applications, including one-dimensional TFBG vibroscopes, accelerometers and micro-displacement sensors; two-dimensional TFBG vector vibroscopes and vector rotation sensors; reflective TFBG refractometers with in-fiber and fiber-to-fiber configurations; polarimetric and plasmonic TFBG biochemical sensors for in-situ detection of cell, protein and glucose.

  19. The Histopathological Parameters Affecting Biochemical Recurrence in Radical Prostatectomies.

    PubMed

    Dere, Yelda; Altinboga, Aysegu Aksoy; Bal, Kaan; Calli, Aylin; Ermete, Murat; Sari, Aysegul Akder

    2017-04-01

    To determine the relationship between biochemical recurrence and other histopathological factors in prostate cancer. Analytical study. Pathology and Urology Departments, Izmir Ataturk Training and Research Hospital, between 2001 - 2013. 117 cases diagnosed with prostatic adenocarcinoma and treated by radical prostatectomy were reviewed retrospectively for histopathological features; whereas, other prognostic findings were noted. PSA levels and many other histopathological parameters were assessed in order to put forth their effect on biochemical recurrence. PSA level (p<0.001), tumor volume (p<0.001), Gleason score (p<0.001), extraprostatic extension (p<0.001), perineural invasion (p<0.001), ganglion involvement (p=0.040), vascular invasion (p<0.001), positive surgical margins (p<0.001), presence of tertiary pattern (p=0.004) and the involvement of the seminal vesicles (p<0.001) were found to be statistically related to the pathological stage. Age, perineural invasion, high grade tertiary pattern, intraluminal mucin, collagenous micronodules and foamy cytoplasmic changes were unrelated to recurrence. Histopathological features can be helpful in predicting prognosis in prostatic adenocarcinomas. However some of the histopathological factors such as intraluminal mucin and foamy cytoplasmic changes may not reflect high recurrence.

  20. Biochemical Studies of Olfaction: Role of Cilia in Odorant Recognition

    PubMed Central

    Rhein, L. D.

    1983-01-01

    Chemoreception in vertebrates is beginning to be understood. Numerous anatomical, behavioral, and physiological studies are now available. Current research efforts are examining the molecular basis of chemoreception. Rainbow trout (Salmo gairdneri) have a functional olfactory system and are a suitable vertebrate model for studying odorant interactions with receptors. Using a biochemical approach, initial events of olfactory recognition were examined; the aim was to determine the location and specificity of odor receptors. Cilia occupy the distal region of the receptor neuron on the trout olfactory epithelium, and their membranes are the postulated locus of odorant receptor sites. A cilia preparation was isolated from the olfactory rosette. The preparation was characterized by quantifying biochemical markers for cilia, along with electron microscopy, all of which substantiated enrichment of cilia. Functional activity was assessed by quantifying binding of several radioactively labeled odorant amino acids. The odorants bound to the cilia in a manner similar to the sedimentable preparation previously isolated from t h e olfactory rosette of the same animal, thus verifying the presence of odor receptors in the cilia preparation. Evidence also confirmed a site TSA which binds L-threonine, L-serine, and L-alanine and a site L which binds L-lysine (and L-arginine). Binding of L-serine and D-alanine showed evidence for a single affinity site while the others showed two affinity sites. Separation of membrane fractions from the cilia preparation revealed that binding activity is associated with a very low density membrane fraction B. PMID:19295786

  1. A multilayer biochemical dry deposition model. 1. Model formulation

    NASA Astrophysics Data System (ADS)

    Wu, Yihua; Brashers, Bart; Finkelstein, Peter L.; Pleim, Jonathan E.

    2003-01-01

    A multilayer biochemical dry deposition model has been developed based on the NOAA Multilayer Model (MLM; [1998]) to study gaseous exchanges between the soil, plants, and the atmosphere. Most of the parameterizations and submodels have been updated or replaced. The numerical integration was improved, and an aerodynamic resistance based on Monin-Obukhov theory was added. An appropriate parameterization for the leaf boundary layer resistance was chosen. A biochemical stomatal resistance model was chosen based on comparisons of four different existing stomatal resistance schemes. It describes photosynthesis and respiration and their coupling with stomatal resistance for sunlit and shaded leaves separately. Various aspects of the photosynthetic process in both C3 and C4 plants are considered in the model. To drive the photosynthesis model, the canopy radiation scheme has been updated. Leaf area index measurements are adjusted to account for stem area index. A normalized soil water stress factor was applied to potential photosynthesis to account for plant response to both drought and water-logging stresses. A new cuticle resistance model was derived based on membrane passive transport theory and Fick's first law. It accounts for the effects of diffusivity and solubility of specific gases in the cuticle membrane, as well as the thickness of the cuticle membrane. The model is designed for use in the nationwide dry deposition networks, for example, the Clean Air Status And Trends Network (CASTNet), and mesoscale models, for example, the Community Multiscale Air Quality model (CMAQ) and even the Weather Research and Forecasting model (WRF).

  2. Balanced Biochemical Reactions: A New Approach to Unify Chemical and Biochemical Thermodynamics

    PubMed Central

    Sabatini, Antonio; Vacca, Alberto; Iotti, Stefano

    2012-01-01

    A novel procedure is presented which, by balancing elements and electric charge of biochemical reactions which occur at constant pH and pMg, allows assessing the thermodynamics properties of reaction ΔrG′0, ΔrH′0, ΔrS′0 and the change in binding of hydrogen and magnesium ions of these reactions. This procedure of general applicability avoids the complex calculations required by the use of the Legendre transformed thermodynamic properties of formation ΔfG′0, ΔfH′0 and ΔfS′0 hitherto considered an obligatory prerequisite to deal with the thermodynamics of biochemical reactions. As a consequence, the term “conditional” is proposed in substitution of “Legendre transformed” to indicate these thermodynamics properties. It is also shown that the thermodynamic potential G is fully adequate to give a criterion of spontaneous chemical change for all biochemical reactions and then that the use of the Legendre transformed G′ is unnecessary. The procedure proposed can be applied to any biochemical reaction, making possible to re-unify the two worlds of chemical and biochemical thermodynamics, which so far have been treated separately. PMID:22247780

  3. Balanced biochemical reactions: a new approach to unify chemical and biochemical thermodynamics.

    PubMed

    Sabatini, Antonio; Vacca, Alberto; Iotti, Stefano

    2012-01-01

    A novel procedure is presented which, by balancing elements and electric charge of biochemical reactions which occur at constant pH and pMg, allows assessing the thermodynamics properties of reaction Δ(r)G'⁰, Δ(r)H'⁰, Δ(r)S'⁰ and the change in binding of hydrogen and magnesium ions of these reactions. This procedure of general applicability avoids the complex calculations required by the use of the Legendre transformed thermodynamic properties of formation Δ(f)G'⁰, Δ(f)H'⁰ and Δ(f)S'⁰ hitherto considered an obligatory prerequisite to deal with the thermodynamics of biochemical reactions. As a consequence, the term "conditional" is proposed in substitution of "Legendre transformed" to indicate these thermodynamics properties. It is also shown that the thermodynamic potential G is fully adequate to give a criterion of spontaneous chemical change for all biochemical reactions and then that the use of the Legendre transformed G' is unnecessary. The procedure proposed can be applied to any biochemical reaction, making possible to re-unify the two worlds of chemical and biochemical thermodynamics, which so far have been treated separately.

  4. Biochemical filter with sigmoidal response: increasing the complexity of biomolecular logic.

    PubMed

    Privman, Vladimir; Halámek, Jan; Arugula, Mary A; Melnikov, Dmitriy; Bocharova, Vera; Katz, Evgeny

    2010-11-11

    The first realization of a designed, rather than natural, biochemical filter process is reported and analyzed as a promising network component for increasing the complexity of biomolecular logic systems. Key challenge in biochemical logic research has been achieving scalability for complex network designs. Various logic gates have been realized, but a "toolbox" of analog elements for interconnectivity and signal processing has remained elusive. Filters are important as network elements that allow control of noise in signal transmission and conversion. We report a versatile biochemical filtering mechanism designed to have sigmoidal response in combination with signal-conversion process. Horseradish peroxidase-catalyzed oxidation of chromogenic electron donor by H(2)O(2) was altered by adding ascorbate, allowing to selectively suppress the output signal, modifying the response from convex to sigmoidal. A kinetic model was developed for evaluation of the quality of filtering. The results offer improved capabilities for design of scalable biomolecular information processing systems.

  5. Influence of low-frequency vibration on changes of biochemical parameters of living rats

    NASA Astrophysics Data System (ADS)

    Kasprzak, Cezary; Damijan, Zbigniew; Panuszka, Ryszard

    2004-05-01

    The aim of the research was to investigate how some selected biochemical parameters of living rats depend on exposure of low-frequency vibrations. Experiments were run on 30 Wistar rats randomly segregated into three groups: (I) 20 days old (before puberty), (II) 70th day after; (III) control group. The exposure was repeated seven times, for 3 h, at the same time of day. Vibrations applied during the first tests of the experiment had acceleration 1.22 m/s2 and frequency 20 Hz. At the 135th day the rats' bones were a subject of morphometric/biochemical examination. The results of biochemical tests proved decrease in LDL and HDL cholesterol levels for exposed rats as well as the Ca contents in blood plasma. There was evident increasing of Ca in blood plasma in exposed rats for frequency of exposition.

  6. CADLIVE toolbox for MATLAB: automatic dynamic modeling of biochemical networks with comprehensive system analysis.

    PubMed

    Inoue, Kentaro; Maeda, Kazuhiro; Miyabe, Takaaki; Matsuoka, Yu; Kurata, Hiroyuki

    2014-09-01

    Mathematical modeling has become a standard technique to understand the dynamics of complex biochemical systems. To promote the modeling, we had developed the CADLIVE dynamic simulator that automatically converted a biochemical map into its associated mathematical model, simulated its dynamic behaviors and analyzed its robustness. To enhance the feasibility by CADLIVE and extend its functions, we propose the CADLIVE toolbox available for MATLAB, which implements not only the existing functions of the CADLIVE dynamic simulator, but also the latest tools including global parameter search methods with robustness analysis. The seamless, bottom-up processes consisting of biochemical network construction, automatic construction of its dynamic model, simulation, optimization, and S-system analysis greatly facilitate dynamic modeling, contributing to the research of systems biology and synthetic biology. This application can be freely downloaded from http://www.cadlive.jp/CADLIVE_MATLAB/ together with an instruction.

  7. Autonomous bio-chemical decontaminator (ABCD) against weapons of mass destruction

    NASA Astrophysics Data System (ADS)

    Hyacinthe, Berg P.

    2006-05-01

    The proliferation of weapons of mass destruction (WMD) and the use of such elements pose an eminent asymmetric threat with disastrous consequences to the national security of any nation. In particular, the use of biochemical warfare agents against civilians and unprotected troops in international conflicts or by terrorists against civilians is considered as a very peculiar threat. Accordingly, taking a quarantine-before-inhalation approach to biochemical warfare, the author introduces the notion of autonomous biochemical decontamination against WMD. In the unfortunate event of a biochemical attack, the apparatus proposed herein is intended to automatically detect, identify, and more importantly neutralize a biochemical threat. Along with warnings concerning a cyber-WMD nexus, various sections cover discussions on human senses and computer sensors, corroborating evidence related to detection and neutralization of chemical toxins, and cyber-assisted olfaction in stand alone, peer-to-peer, and network settings. In essence, the apparatus can be used in aviation and mass transit security to initiate mass decontamination by dispersing a decontaminant aerosol or to protect the public water supply against a potential bioterrorist attack. Future effort may involve a system-on-chip (SoC) embodiment of this apparatus that allows a safer environment for the emerging phenomenon of cyber-assisted olfaction and morph cell phones into ubiquitous sensors/decontaminators. Although this paper covers mechanisms and protocols to avail a neutralizing substance, further research will need to explore the substance's various pharmacological profiles and potential side effects.

  8. Mechanisms of Ovarian Cancer Metastasis: Biochemical Pathways

    PubMed Central

    Nakayama, Kentaro; Nakayama, Naomi; Katagiri, Hiroshi; Miyazaki, Kohji

    2012-01-01

    Ovarian cancer is the most lethal gynecologic malignancy. Despite advances in chemotherapy, the five-year survival rate of advanced ovarian cancer patients with peritoneal metastasis remains around 30%. The most significant prognostic factor is stage, and most patients present at an advanced stage with peritoneal dissemination. There is often no clearly identifiable precursor lesion; therefore, the events leading to metastatic disease are poorly understood. This article reviews metastatic suppressor genes, the epithelial-mesenchymal transition (EMT), and the tumor microenvironment as they relate to ovarian cancer metastasis. Additionally, novel chemotherapeutic agents targeting the metastasis-related biochemical pathways are discussed. PMID:23109879

  9. Physiological and biochemical changes with Vamana procedure

    PubMed Central

    Gupta, Bharti; Mahapatra, Sushil C.; Makhija, Renu; Kumar, Adarsh; Jirankalgikar, Nikhil M.; Padhi, Madan M.; Devalla, Ramesh Babu

    2012-01-01

    Vamana Karma (therapeutic emesis) primarily a Samshodhana Karma (purification procedure) is one of the five Pradhana Karmas (chief procedures) of Panchakarma. It is mentioned in Ayurvedic texts that a person after Samyak Vamana (proper Vamana) experiences lightness of the body, Hrit (precordium), Kantha (throat/voice), and Shirah (head) and weakness. This procedure is effectively used in healthy and ailing persons for purification of body and extraction of Doshas (especially Kapha) in Ayurvedic system. It has been found worth to observe the physiological and biochemical changes during Vamana and after the procedure to understand the effect/safety margins of the procedure in healthy volunteers. PMID:23723640

  10. Noise-induced metastability in biochemical networks.

    PubMed

    Biancalani, Tommaso; Rogers, Tim; McKane, Alan J

    2012-07-01

    Intracellular biochemical reactions exhibit a rich dynamical phenomenology which cannot be explained within the framework of mean-field rate equations and additive noise. Here, we show that the presence of metastable states and radically different time scales are general features of a broad class of autocatalytic reaction networks, and that this fact may be exploited to gain analytical results. The latter point is demonstrated by a treatment of the paradigmatic Togashi-Kaneko reaction, which has resisted theoretical analysis for the last decade.

  11. Azoospermia: clinical, hormonal, and biochemical investigation.

    PubMed

    Papadimas, J; Papadopoulou, F; Ioannidis, S; Spanos, E; Tarlatzis, B; Bontis, J; Mantalenakis, S

    1996-01-01

    The aim of this study was to evaluate the clinical, hormonal and biochemical characteristics of infertile men with azoospermia. A total of 187 azoospermic out of 2610 infertile men (7.2%) were studied. Mean testicular volume and basal plasma levels of FSH were the most useful parameters concerning the evaluation of azoospermia. Basal plasma levels of LH and T were useful only in azoospermic men with hypogonadism, whereas plasma PRL levels, semen volume, and seminal plasma fructose levels were not found to be of common use except in selected cases.

  12. Sampling rare switching events in biochemical networks.

    PubMed

    Allen, Rosalind J; Warren, Patrick B; Ten Wolde, Pieter Rein

    2005-01-14

    Bistable biochemical switches are widely found in gene regulatory networks and signal transduction pathways. Their switching dynamics are difficult to study, however, because switching events are rare, and the systems are out of equilibrium. We present a simulation method for predicting the rate and mechanism of the flipping of these switches. We apply it to a genetic switch and find that it is highly efficient. The path ensembles for the forward and reverse processes do not coincide. The method is widely applicable to rare events and nonequilibrium processes.

  13. [Chronic fatigue syndrome: biochemical examination of blood].

    PubMed

    Hakariya, Yukiko; Kuratsune, Hirohiko

    2007-06-01

    Though patients with chronic fatigue syndrome (CFS) have lots of complaints, abnormal findings cannot be detected by biochemical screening tests. However, some specialized blood tests have revealed neuroendocrine immune axis abnormalities, which is closely associated with each other. Recent studies indicate that CFS can be understood as a special condition based on abnormality of the psycho-neuro-endocrino-immunological system, with the distinguishing feature of CFS seeming to be the secondary brain dysfunction caused by several cytokines and/or autoantibodies. In this paper, we summarize these abnormalities found in CFS and show the neuro-molecular mechanism leading to chronic fatigue.

  14. Biochemical processing of heavy oils and residuum

    SciTech Connect

    Lin, M.S.; Premuzic, T.; Yablon, J.H.; Zhou, Wei-Min

    1995-05-01

    During the past several decades, the petroleum industry has adjusted gradually to accommodate the changes in market product demands, government regulations, and the quality and cost of feedstock crude oils. For example, the trends show that the demand for distillate fuels, such as diesel, as compared to gasoline are increasing. Air-quality standards have put additional demand on the processing of heavier and higher sulfur feed stocks. Thus, the 1990 Clean Air Act amendments require the industry to produce greater quantities of oxygenated gasoline, and lower sulfur diesel and reformulated gasoline. Biochemical technology may play an important role in responding to these demands on the petroleum industry.

  15. [Optical detection system for micro biochemical analyses].

    PubMed

    Li, Feng; Wu, Yi-hui; Zhao, Hua-bing; Ju, Hui

    2005-04-01

    For the need of biochemical chip, which consumes fewer specimens and is easy to integrate with micro-fluid chip, two kinds of spectrophotometric analysis methods are described in the present paper. Both the direct detection method and evanescent wave detection method are used in the experiments with visible light (460-800 nm). The experimental results proved that the direct detection is simple and evident; on the other hand the evanescent wave detection method consumes much less reagent and is easy to integrate with microchips.

  16. Synchronization of stochastic oscillators in biochemical systems.

    PubMed

    Challenger, Joseph D; McKane, Alan J

    2013-07-01

    We investigate the synchronization of stochastic oscillations in biochemical models by calculating the complex coherence function within the linear noise approximation. The method is illustrated on a simple example and then applied to study the synchronization of chemical concentrations in social amoeba. The degree to which variation of rate constants in different cells and the volume of the cells affects synchronization of the oscillations is explored and the phase lag calculated. In all cases the analytical results are shown to be in good agreement with those obtained through numerical simulations.

  17. Preterm labour. Biochemical and endocrinological preparation for parturition.

    PubMed

    Terzidou, Vasso

    2007-10-01

    Preterm delivery is a common obstetric problem occurring in about 1 in 10 of all births. Preterm babies have a high risk of morbidity and mortality. Such births account for 75% of all major neonatal problems. At the other end of the spectrum, prolonged pregnancy is also a subject of concern because it too is associated with increased fetal morbidity and mortality. Despite extensive research, the mechanisms that control the length of human pregnancy and signal the onset of labour have not been fully determined. This chapter will discuss basic principles in the biology of parturition and the regulation of contraction-associated proteins including the oxytocin receptor. The major pathways regulating contractions and the transcriptional regulation of the main genes that are known to be involved in the onset of labour and parturition will be examined. Some new potentially therapeutic strategies for the biochemical management of preterm labour will be discussed.

  18. Guiding lights: recent developments in optogenetic control of biochemical signals.

    PubMed

    Yin, Taofei; Wu, Yi I

    2013-03-01

    Optogenetics arises from the innovative application of microbial opsins in mammalian neurons and has since been a powerful technology that fuels the advance of our knowledge in neuroscience. In recent years, there has been growing interest in designing optogenetic tools extendable to broader cell types and biochemical signals. To date, a variety of photoactivatable proteins (refers to induction of protein activity in contrast to fluorescence) have been developed based on the understanding of plant and microbial photoreceptors including phototropins, blue light sensors using flavin adenine dinucleotide proteins, cryptochromes, and phytochromes. Such tools offered researchers reversible, quantitative, and precise spatiotemporal control of enzymatic activity, protein-protein interaction, protein translocation, as well as gene transcription in cells and in whole animals. In this review, we will briefly introduce these photosensory proteins, describe recent developments in optogenetics, and compare and contrast different methods based on their advantages and limitations.

  19. Biochemical paths in humans and cells: Frontiers of AMS bioanalysis

    NASA Astrophysics Data System (ADS)

    Vogel, J. S.; Palmblad, N. M.; Ognibene, T.; Kabir, M. M.; Buchholz, B. A.; Bench, G.

    2007-06-01

    The publication rate of 3H and 14C use in biomedical research decreased by a factor of three since 1990 when the first applications of AMS in biomedicine were published. Against this decrease, the high sensitivity of AMS for these isotopes in small isolated samples has made significant contributions. New smaller spectrometers and increased commercial availability of AMS have solved some of the issues surrounding availability and cost, but improved quantitation in non-isotopic methods now compete with some early uses of AMS. We review the strength of AMS for quantifying rare biochemical events and chemical passages through individual people or cells and consider these as the frontiers of quantitation leading to profitable science unavailable to other techniques.

  20. Biochemical, endocrine, and hematological factors in human oxygen tolerance extension: Predictive studies 6

    NASA Technical Reports Server (NTRS)

    Lambertsen, C. J.; Clark, J. M.

    1992-01-01

    The Predictive Studies VI (Biochemical, endocrine, and hematological factors in human oxygen tolerance extension) Program consisted of two related areas of research activity, integrated in design and performance, that were each based on an ongoing analysis of human organ oxygen tolerance data obtained for the continuous oxygen exposures of the prior Predictive Studies V Program. The two research areas effectively blended broad investigation of systematically varied intermittent exposure patterns in animals with very selective evaluation of specific exposure patterns in man.

  1. BIOCHEMICAL PROCESSES FOR GEOTHERMAL BRINE TREATMENT

    SciTech Connect

    PREMUZIC,E.T.; LIN,M.S.; BOHENEK,M.; JOSHI-TOPE,G.; ZHOU,W.; SHELENKOVA,L.; WILKE,R.

    1998-09-20

    As part of the DOE Geothermal Energy Program, BNL's Advanced Biochemical Processes for Geothermal Brines (ABPGB) project is aimed at the development of cost-efficient and environmentally acceptable technologies for the disposal of geothermal wastes. Extensive chemical studies of high and low salinity brines and precipitates have indicated that in addition to trace quantities of regulated substances, e.g., toxic metals such as arsenic and mercury, there are significant concentrations of valuable metals, including gold, silver and platinum. Further chemical and physical studies of the silica product have also shown that the produced silica is a valuable material with commercial potential. A combined biochemical and chemical technology is being developed which (1) solubilizes, separates, and removes environmentally regulated constituents in geothermal precipitates and brines (2) generates an amorphous silica product which may be used as feedstock for the production of revenue generating materials, (3) recover economically valuable trace metals and salts. Geothermal power resources which utilize low salinity brines and use the Stretford process for hydrogen sulfide abatement generate a contaminated sulfur cake. Combined technology converts such sulfur to a commercial grade sulfur, suitable for agricultural use. The R and D activities at BNL are conducted jointly with industrial parties in an effort focused on field applications.

  2. Biochemical processes for geothermal brine treatment

    SciTech Connect

    Premuzic, E.T.; Lin, M.S.; Bohenek, M.; Joshi-Tope, G.; Zhou, W.; Shelenkova, L.; Wilke, R.

    1998-08-01

    As part of the DOE Geothermal Energy Program, BNL`s Advanced Biochemical Processes for Geothermal Brines (ABPGB) project is aimed at the development of cost-efficient and environmentally acceptable technologies for the disposal of geothermal wastes. Extensive chemical studies of high and low salinity brines and precipitates have indicated that in addition to trace quantities of regulated substances, e.g., toxic metals such as arsenic and mercury, there are significant concentrations of valuable metals, including gold, silver and platinum. Further chemical and physical studies of the silica product have also shown that the produced silica is a valuable material with commercial potential. A combined biochemical and chemical technology is being developed which (1) solubilizes, separates, and removes environmentally regulated constituents in geothermal precipitates and brines, (2) generates an amorphous silica product which may be used as feedstock for the production of revenue generating materials, (3) recover economically valuable trace metals and salts. Geothermal power resources which utilize low salinity brines and use the Stretford process for hydrogen sulfide abatement generate a contaminated sulfur cake. Combined technology converts such sulfur to a commercial grade sulfur, suitable for agricultural use. The R and D activities at BNL are conducted jointly with industrial parties in an effort focused on field applications.

  3. Biochemical effects of oral sodium phosphate.

    PubMed

    DiPalma, J A; Buckley, S E; Warner, B A; Culpepper, R M

    1996-04-01

    Our objective was to monitor serum and urine biochemical changes after oral sodium phosphate cleansing in a prospectively designed study. The study subjects were seven healthy, asymptomatic adults. Sodium phosphate 45 ml diluted in 45 ml water was given orally at baseline and 12 hr later. Calcium, ionized calcium, phosphorus, sodium, potassium, creatinine, and PTH were analyzed at 2, 4, 6, 9, 12, 14, 16, 18, 21 and 24 hr after the first challenge. Urinary calcium, phosphorus, sodium, potassium, and cyclic AMP were analyzed at baseline and every 2 hr after oral sodium phosphate. Blood pressure, pulse, and respiratory rate were recorded every 2 hr and symptom questionnaires using visual analog scales were completed. A marked rise in phosphorus (peak range 3.6-12.4 mg/dl, P < 0.001) and falls in calcium (P < 0.001) and ionized calcium (P < 0.001) were seen. Rises seen in PTH and urinary cAMP confirmed the physiologic significance of the biochemical effect. There were no significant changes in other serum and urine laboratory or clinical assessments. Reported significant symptoms included bloating, cramps, abdominal pain, and nausea. Significant hypocalcemia and hyperphosphatemia after oral sodium phosphate raises concern about its use in normal individuals. Oral sodium phosphate should not be administered in patients with cardiopulmonary, renal, or hepatic disease.

  4. Rebinding in biochemical reactions on membranes

    NASA Astrophysics Data System (ADS)

    Lawley, Sean D.; Keener, James P.

    2017-10-01

    The behavior of many biochemical processes depends crucially on molecules rapidly rebinding after dissociating. In the case of multisite protein modification, the importance of rebinding has been demonstrated both experimentally and through several recent computational studies involving stochastic spatial simulations. As rebinding stems from spatio-temporal correlations, theorists have resorted to models that explicitly include space to properly account for the effects of rebinding. However, for reactions in three space dimensions it was recently shown that well-mixed ordinary differential equation (ODE) models can incorporate rebinding by adding connections to the reaction network. The rate constants for these new connections involve the probability that a pair of molecules rapidly rebinds after dissociation. In order to study biochemical reactions on membranes, in this paper we derive an explicit formula for this rebinding probability for reactions in two space dimensions. We show that ODE models can use the formula to replicate detailed stochastic spatial simulations, and that the formula can predict ultrasensitivity for reactions involving multisite modification of membrane-bound proteins. Further, we compute a new concentration-dependent rebinding probability for reactions in three space dimensions. Our analysis predicts that rebinding plays a much larger role in reactions on membranes compared to reactions in cytoplasm.

  5. Biochemical basis for the biological clock

    NASA Technical Reports Server (NTRS)

    Morre, D. James; Chueh, Pin-Ju; Pletcher, Jake; Tang, Xiaoyu; Wu, Lian-Ying; Morre, Dorothy M.

    2002-01-01

    NADH oxidases at the external surface of plant and animal cells (ECTO-NOX proteins) exhibit stable and recurring patterns of oscillations with potentially clock-related, entrainable, and temperature-compensated period lengths of 24 min. To determine if ECTO-NOX proteins might represent the ultradian time keepers (pacemakers) of the biological clock, COS cells were transfected with cDNAs encoding tNOX proteins having a period length of 22 min or with C575A or C558A cysteine to alanine replacements having period lengths of 36 or 42 min. Here we demonstrate that such transfectants exhibited 22, 36, or 40 to 42 h circadian patterns in the activity of glyceraldehyde-3-phosphate dehydrogenase, a common clock-regulated protein, in addition to the endogenous 24 h circadian period length. The fact that the expression of a single oscillatory ECTO-NOX protein determines the period length of a circadian biochemical marker (60 X the ECTO-NOX period length) provides compelling evidence that ECTO-NOX proteins are the biochemical ultradian drivers of the cellular biological clock.

  6. Clinical, biochemical & cytomorphologic study on Hashimoto's thyroiditis

    PubMed Central

    Thomas, Tina; Sreedharan, Suja; Khadilkar, Urmila N.; Deviprasad, D; Kamath, M. Panduranga; Bhojwani, Kiran M.; Alva, Arathi

    2014-01-01

    Background & objectives: Despite, the extensive salt iodization programmes implemented in India, the prevalence of goiter has not reduced much in our country. The most frequent cause of hypothyroidism and goiter in iodine sufficient areas is Hashimoto's thyroiditis (HT). This study records the clinical presentation, biochemical status, ultrasonographic picture and cytological appearance of this disease in a coastal endemic zone for goiter. Methods: Case records of patients with cytological diagnosis of HT were studied in detail, with reference to their symptoms, presence of goiter, thyroid function status, antibody levels and ultrasound picture. Detailed cytological study was conducted in selected patients. Results: A total of 144 patients with cytological proven HT/lymphocytic thyroiditis were studied. Ninety per cent of the patients were females and most of them presented within five years of onset of symptoms. Sixty eight per cent patients had diffuse goiter, 69 per cent were clinically euthyroid and 46 per cent were biochemically mildly hypothyroid. Antibody levels were elevated in 92.3 per cent cases. In majority of patients the sonographic picture showed heterogeneous echotexture with increased vascularity. Cytological changes were characteristic. Interpretation & conclusions: Our study showed predominance of females in the study population in 21-40 yr age group with diffuse goiter. We suggest that in an endemic zone for goiter, all women of the child bearing age should be screened for HT. PMID:25758571

  7. [Biochemical principles of early saturnism recognition].

    PubMed

    Tsimakuridze, M P; Mansuradze, E A; Zurashvili, D G; Tsimakuridze, M P

    2009-03-01

    The aim of the work is to determine the major sensitive criteria of biochemical indicators that allow timely discovery of negative influence of lead on organism and assist in early diagnosis of primary stages of saturnism. The workers of Georgian typographies, performing technological processes of letterpress printing were observed. Professional groups having contact with lead aerosols (main group of 66 people) and the workers of the same typography not being in touch with the poison (control group of 24 people) were studied. It was distinguished that, protracted professional contact with lead causes moderate increase of lead, coproporphyrin and DALA in daily urine in most cases; it is more clearly evidenced in the professional groups of lead smelters and lino operators and less clearly among typesetter and printers. Upon the checkup of people, having a direct contact with lead, biochemical analysis of urine should be given a preference, especially the determination of quantitative content of lead and coproporphyrin in urine with the aim of revealing the lead carrier, which is one of the first signals for occupational lookout and medical monitoring of the similar contingent.

  8. Biochemical basis for the biological clock

    NASA Technical Reports Server (NTRS)

    Morre, D. James; Chueh, Pin-Ju; Pletcher, Jake; Tang, Xiaoyu; Wu, Lian-Ying; Morre, Dorothy M.

    2002-01-01

    NADH oxidases at the external surface of plant and animal cells (ECTO-NOX proteins) exhibit stable and recurring patterns of oscillations with potentially clock-related, entrainable, and temperature-compensated period lengths of 24 min. To determine if ECTO-NOX proteins might represent the ultradian time keepers (pacemakers) of the biological clock, COS cells were transfected with cDNAs encoding tNOX proteins having a period length of 22 min or with C575A or C558A cysteine to alanine replacements having period lengths of 36 or 42 min. Here we demonstrate that such transfectants exhibited 22, 36, or 40 to 42 h circadian patterns in the activity of glyceraldehyde-3-phosphate dehydrogenase, a common clock-regulated protein, in addition to the endogenous 24 h circadian period length. The fact that the expression of a single oscillatory ECTO-NOX protein determines the period length of a circadian biochemical marker (60 X the ECTO-NOX period length) provides compelling evidence that ECTO-NOX proteins are the biochemical ultradian drivers of the cellular biological clock.

  9. Surface Modification of Gold Nanoparticles with Small Molecules for Biochemical Analysis.

    PubMed

    Chen, Yiping; Xianyu, Yunlei; Jiang, Xingyu

    2017-02-21

    accessibility of small molecules on AuNPs in most cases can be precisely controlled without compromising their bioactivity as well, thus ensuring the performance, such as the specificity and sensitivity, of AuNP-based biochemical assays. This Account reviews recent progress in the surface chemistry of functionalized AuNPs for biochemical assays. The surface chemistries mainly include click chemistry, ligand exchange reaction, and coordination-based recognition. These surface-modified AuNPs allow for assaying a range of important biochemical markers including metal ions, small biomolecules, enzymes, and antigens and antibodies. Applications of these systems range from environmental monitoring to medical diagnostics. This Account highlights the advantages and limitations (sensitivity, detection efficiency, and stability) that AuNP-mediated assays still have compared with conventional analytical methods. This Account also discusses the future research directions of surface-modified AuNP-mediated biochemical analysis. The main aim of this Account is to summarize the current surface modification strategies for AuNPs and further demonstrate how to make use of surface modification strategies to effectively improve the performance of AuNP-mediated analytical methods for a wide variety of applications relating to biochemical analysis.

  10. Identifying biochemical phenotypic differences between cryptic species

    PubMed Central

    Liebeke, Manuel; Bruford, Michael W.; Donnelly, Robert K.; Ebbels, Timothy M. D.; Hao, Jie; Kille, Peter; Lahive, Elma; Madison, Rachael M.; Morgan, A. John; Pinto-Juma, Gabriela A.; Spurgeon, David J.; Svendsen, Claus; Bundy, Jacob G.

    2014-01-01

    Molecular genetic methods can distinguish divergent evolutionary lineages in what previously appeared to be single species, but it is not always clear what functional differences exist between such cryptic species. We used a metabolomic approach to profile biochemical phenotype (metabotype) differences between two putative cryptic species of the earthworm Lumbricus rubellus. There were no straightforward metabolite biomarkers of lineage, i.e. no metabolites that were always at higher concentration in one lineage. Multivariate methods, however, identified a small number of metabolites that together helped distinguish the lineages, including uncommon metabolites such as Nε-trimethyllysine, which is not usually found at high concentrations. This approach could be useful for characterizing functional trait differences, especially as it is applicable to essentially any species group, irrespective of its genome sequencing status. PMID:25252836

  11. Identifying biochemical phenotypic differences between cryptic species.

    PubMed

    Liebeke, Manuel; Bruford, Michael W; Donnelly, Robert K; Ebbels, Timothy M D; Hao, Jie; Kille, Peter; Lahive, Elma; Madison, Rachael M; Morgan, A John; Pinto-Juma, Gabriela A; Spurgeon, David J; Svendsen, Claus; Bundy, Jacob G

    2014-09-01

    Molecular genetic methods can distinguish divergent evolutionary lineages in what previously appeared to be single species, but it is not always clear what functional differences exist between such cryptic species. We used a metabolomic approach to profile biochemical phenotype (metabotype) differences between two putative cryptic species of the earthworm Lumbricus rubellus. There were no straightforward metabolite biomarkers of lineage, i.e. no metabolites that were always at higher concentration in one lineage. Multivariate methods, however, identified a small number of metabolites that together helped distinguish the lineages, including uncommon metabolites such as Nε-trimethyllysine, which is not usually found at high concentrations. This approach could be useful for characterizing functional trait differences, especially as it is applicable to essentially any species group, irrespective of its genome sequencing status. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  12. Hemoglobin Variants: Biochemical Properties and Clinical Correlates

    PubMed Central

    Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J.

    2013-01-01

    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples. PMID:23388674

  13. Thin membrane sensor with biochemical switch

    NASA Technical Reports Server (NTRS)

    Case, George D. (Inventor); Worley, III, Jennings F. (Inventor)

    1994-01-01

    A modular biosensor system for chemical or biological agent detection utilizes electrochemical measurement of an ion current across a gate membrane triggered by the reaction of the target agent with a recognition protein conjugated to a channel blocker. The sensor system includes a bioresponse simulator or biochemical switch module which contains the recognition protein-channel blocker conjugate, and in which the detection reactions occur, and a transducer module which contains a gate membrane and a measuring electrode, and in which the presence of agent is sensed electrically. In the poised state, ion channels in the gate membrane are blocked by the recognition protein-channel blocker conjugate. Detection reactions remove the recognition protein-channel blocker conjugate from the ion channels, thus eliciting an ion current surge in the gate membrane which subsequently triggers an output alarm. Sufficiently large currents are generated that simple direct current electronics are adequate for the measurements. The biosensor has applications for environmental, medical, and industrial use.

  14. Droplet microfluidics in (bio)chemical analysis.

    PubMed

    Basova, Evgenia Yu; Foret, Frantisek

    2015-01-07

    Droplet microfluidics may soon change the paradigm of performing chemical analyses and related instrumentation. It can improve not only the analysis scale, possibility for sensitivity improvement, and reduced consumption of chemical and biological reagents, but also the speed of performing a variety of unit operations. At present, microfluidic platforms can reproducibly generate monodisperse droplet populations at kHz or higher rates with droplet sizes suitable for high-throughput experiments, single-cell detection or even single molecule analysis. In addition to being used as microreactors with volume in the micro- to femtoliter range, droplet based systems have also been used to directly synthesize particles and encapsulate biological entities for biomedicine and biotechnology applications. This minireview summarizes various droplet microfluidics operations and applications for (bio)chemical assays described in the literature during the past few years.

  15. Highly valuable microalgae: biochemical and topological aspects.

    PubMed

    Pignolet, Olivier; Jubeau, Sébastien; Vaca-Garcia, Carlos; Michaud, Philippe

    2013-08-01

    The past decade has seen a surge in the interest in microalgae culture for biodiesel production and other applications as renewable biofuels as an alternative to petroleum transport fuels. The development of new technologies for the culture of these photosynthetic microorganisms and improved knowledge of their biochemical composition has spurred innovation in the field of high-value biomolecules. These developments are only economically viable if all the microalgae fractions are valorized in a biorefinery strategy. Achieving this objective requires an understanding of microalgae content and the cellular localization of the main biomolecular families in order to develop efficient harvest and sequential recovery technologies. This review summarizes the state of the art in microalgae compositions and topologies using some examples of the main industrially farmed microalgae.

  16. Biochemical Basis of Sestrin Physiological Activities

    SciTech Connect

    Ho, Allison; Cho, Chun-Seok; Namkoong, Sim; Cho, Uhn-Soo; Lee, Jun Hee

    2016-05-10

    Excessive accumulation of reactive oxygen species (ROS) and chronic activation of mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) are well-characterized promoters of aging and age-associated degenerative pathologies. Sestrins, a family of highly conserved stress-inducible proteins, are important negative regulators of both ROS and mTORC1 signaling pathways; however, the mechanistic basis of how Sestrins suppress these pathways remains elusive. In the past couple of years, breakthrough discoveries about Sestrin signaling and its molecular nature have markedly increased our biochemical understanding of Sestrin function. These discoveries have also uncovered new potential therapeutic strategies that may eventually enable us to attenuate aging and age-associated diseases.

  17. Hydrophobic hydrophilic phenomena in biochemical processes.

    PubMed

    Ben-Naim, Arieh

    2003-09-01

    The evolution of concepts developed in the study of the hydrophobic affect is surveyed, within the more general context of solvent-induced effects. A systematic analysis of the solvent-induced contribution to the driving force for the process of protein folding has led to two important modifications in our understanding of these effects. First, the conventional concepts of hydrophobic solvation and hydrophobic interactions had to be replaced by their respective conditional effects. Second, each of the hydrophobic effects has also a corresponding hydrophilic counterpart. Some of the latter effects could contribute significantly to the total driving force for the process of protein folding, and perhaps even dominate the driving force for biochemical processes.

  18. Comparative biochemical studies of carotenoids in catfishes.

    PubMed

    Tsushima, M; Ikuno, Y; Nagata, S; Kodama, K; Matsuno, T

    2002-11-01

    The carotenoids of 12 species of Siluriformes fishes (eight families) were investigated from a comparative biochemical point of view. The patterns of carotenoids in catfishes belonging to the family Siluridae were quite different from those of the other seven families of catfishes (Bagridae, Amblycipitidae, Clariidae, Plotosidae, Ictaluridae, Callichthyidae and Malapteruridae). 7, 8-Dihydro-beta-carotene; 7, 8, 7', 8'- and 7, 8, 9, 10-tetrahydro-beta-carotene; (3R)-7', 8'-dihydro-beta-cryptoxanthin; 7, 8-dihydrolutein A; 7, 8-dihydrolutein B; parasiloxanthin; 7', 8'-dihydroparasiloxanthin; and 4 or 4'-hydroxyparasiloxanthin were characteristic carotenoids found in only one family, Siluridae, and these carotenoids accounted for 24-60% of total carotenoids. In catfishes belonging to the other seven families except Siluridae, the carotenoid patterns were very similar and the most predominant carotenoid was zeaxanthins (23-56%). Copyright 2002 Elsevier Science Inc.

  19. Charge trapping and luminescence in biochemical systems

    NASA Astrophysics Data System (ADS)

    Cooke, D. Wayne

    A review of radiation-induced charge trapping and release in biochemical systems is given. Several techniques appropriate to studying this damage are discussed; electron spin resonance (ESR), electron-nuclear double resonance (ENDOR), optical absorption, muon spin rotation (μSR), and thermally stimulated luminescence (TSL), for example, with the emphasis being on TSL. Experimental aspects of this technique, along with many results from TSL studies of amino acids, proteins, DNA, RNA, and related compounds are reviewed. Specific models derived from analyses of the TSL glow curves and emission spectra are discussed. The overwhelming majority of these studies suggest that electronic deexcitation of the radiation-induced trapped charge occurs via the singlet and triplet manifolds of the molecule.

  20. The biochemical basis of hereditary fructose intolerance.

    PubMed

    Bouteldja, Nadia; Timson, David J

    2010-04-01

    Hereditary fructose intolerance is a rare, but potentially lethal, inherited disorder of fructose metabolism, caused by mutation of the aldolase B gene. Treatment currently relies solely on dietary restriction of problematic sugars. Biochemical study of defective aldolase B enzymes is key to revealing the molecular basis of the disease and providing a stronger basis for improved treatment and diagnosis. Such studies have revealed changes in enzyme activity, stability and oligomerisation. However, linking these changes to disease phenotypes has not always been straightforward. This review gives a general overview of the features of hereditary fructose intolerance, then concentrates on the biochemistry of the AP variant (Ala149Pro variant of aldolase B) and molecular pathological consequences of mutation of the aldolase B gene.

  1. Methylenetetrahydrofolate reductase: biochemical characterization and medical significance.

    PubMed

    Trimmer, Elizabeth E

    2013-01-01

    Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydofolate (CH2-H4folate) to 5-methyltetrahydrofolate (CH3-H4folate). The enzyme employs a noncovalently-bound flavin adenine dinucleotide (FAD), which accepts reducing equivalents from NAD(P)H and transfers them to CH2-H4folate. The reaction provides the sole source of CH3-H4folate, which is utilized by methionine synthase in the synthesis of methionine from homocysteine. MTHFR plays a key role in folate metabolism and in the homeostasis of homocysteine; mutations in the enzyme lead to hyperhomocyst(e)inemia. A common C677T polymorphism in MTHFR has been associated with an increased risk for the development of cardiovascular disease, Alzheimer's disease, and depression in adults, and of neural tube defects in the fetus. The mutation also confers protection for certain types of cancers. This review presents the current knowledge of the enzyme, its biochemical characterization, and medical significance.

  2. Biochemical composition of marine monogenean parasite eggs.

    PubMed

    Brazenor, Alexander K; Francis, David S; Hutson, Kate S; Carton, Alexander G

    2017-08-24

    This study on the eggs of the tropical monogenean Neobenedenia girellae presents the first detailed quantitative biochemical information of a marine parasite species' eggs. Moisture and protein composed the majority of the contents of freshly laid eggs (79.12±0.82 and 11.51±0.49% respectively) followed by lipid (2.50±0.15%). Lipids were composed of approximately equal amounts of saturated, monounsaturated, and polyunsaturated fatty acids and the predominant lipid class was triacylglycerol (33.82±1.20%). This study represents a fundamental step towards a better understanding of the early life biology of this important species of parasite. Copyright © 2017. Published by Elsevier B.V.

  3. Physiological, behavioral and biochemical adaptations of intertidal fishes to hypoxia.

    PubMed

    Richards, Jeffrey G

    2011-01-15

    Hypoxia survival in fish requires a well-coordinated response to either secure more O(2) from the hypoxic environment or to limit the metabolic consequences of an O(2) restriction at the mitochondria. Although there is a considerable amount of information available on the physiological, behavioral, biochemical and molecular responses of fish to hypoxia, very little research has attempted to determine the adaptive value of these responses. This article will review current attempts to use the phylogenetically corrected comparative method to define physiological and behavioral adaptations to hypoxia in intertidal fish and further identify putatively adaptive biochemical traits that should be investigated in the future. In a group of marine fishes known as sculpins, from the family Cottidae, variation in hypoxia tolerance, measured as a critical O(2) tension (P(crit)), is primarily explained by variation in mass-specific gill surface area, red blood cell hemoglobin-O(2) binding affinity, and to a lesser extent variation in routine O(2) consumption rate (M(O(2))). The most hypoxia-tolerant sculpins consistently show aquatic surface respiration (ASR) and aerial emergence behavior during hypoxia exposure, but no phylogenetically independent relationship has been found between the thresholds for initiating these behaviors and P(crit). At O(2) levels below P(crit), hypoxia survival requires a rapid reorganization of cellular metabolism to suppress ATP consumption to match the limited capacity for O(2)-independent ATP production. Thus, it is reasonable to speculate that the degree of metabolic rate suppression and the quantity of stored fermentable fuel is strongly selected for in hypoxia-tolerant fishes; however, these assertions have not been tested in a phylogenetic comparative model.

  4. Diabetes, biochemical markers of bone turnover, diabetes control, and bone.

    PubMed

    Starup-Linde, Jakob

    2013-01-01

    Diabetes mellitus is known to have late complications including micro vascular and macro vascular disease. This review focuses on another possible area of complication regarding diabetes; bone. Diabetes may affect bone via bone structure, bone density, and biochemical markers of bone turnover. The aim of the present review is to examine in vivo from humans on biochemical markers of bone turnover in diabetics compared to non-diabetics. Furthermore, the effect of glycemic control on bone markers and the similarities and differences of type 1- and type 2-diabetics regarding bone markers will be evaluated. A systematic literature search was conducted using PubMed, Embase, Cinahl, and SveMed+ with the search terms: "Diabetes mellitus," "Diabetes mellitus type 1," "Insulin dependent diabetes mellitus," "Diabetes mellitus type 2," "Non-insulin dependent diabetes mellitus," "Bone," "Bone and Bones," "Bone diseases," "Bone turnover," "Hemoglobin A Glycosylated," and "HbA1C." After removing duplicates from this search 1,188 records were screened by title and abstract and 75 records were assessed by full text for inclusion in the review. In the end 43 records were chosen. Bone formation and resorption markers are investigated as well as bone regulating systems. T1D is found to have lower osteocalcin and CTX, while osteocalcin and tartrate-resistant acid are found to be lower in T2D, and sclerostin is increased and collagen turnover markers altered. Other bone turnover markers do not seem to be altered in T1D or T2D. A major problem is the lack of histomorphometric studies in humans linking changes in turnover markers to actual changes in bone turnover and further research is needed to strengthen this link.

  5. Pattern Selection by Dynamical Biochemical Signals

    PubMed Central

    Palau-Ortin, David; Formosa-Jordan, Pau; Sancho, José M.; Ibañes, Marta

    2015-01-01

    The development of multicellular organisms involves cells to decide their fate upon the action of biochemical signals. This decision is often spatiotemporally coordinated such that a spatial pattern arises. The dynamics that drive pattern formation usually involve genetic nonlinear interactions and positive feedback loops. These complex dynamics may enable multiple stable patterns for the same conditions. Under these circumstances, pattern formation in a developing tissue involves a selection process: why is a certain pattern formed and not another stable one? Herein we computationally address this issue in the context of the Notch signaling pathway. We characterize a dynamical mechanism for developmental selection of a specific pattern through spatiotemporal changes of the control parameters of the dynamics, in contrast to commonly studied situations in which initial conditions and noise determine which pattern is selected among multiple stable ones. This mechanism can be understood as a path along the parameter space driven by a sequence of biochemical signals. We characterize the selection process for three different scenarios of this dynamical mechanism that can take place during development: the signal either 1) acts in all the cells at the same time, 2) acts only within a cluster of cells, or 3) propagates along the tissue. We found that key elements for pattern selection are the destabilization of the initial pattern, the subsequent exploration of other patterns determined by the spatiotemporal symmetry of the parameter changes, and the speeds of the path compared to the timescales of the pattern formation process itself. Each scenario enables the selection of different types of patterns and creates these elements in distinct ways, resulting in different features. Our approach extends the concept of selection involved in cellular decision-making, usually applied to cell-autonomous decisions, to systems that collectively make decisions through cell

  6. Psychological and Biochemical Effects of a Stress Management Program,

    DTIC Science & Technology

    risk factors for cardiovascular disease . We wanted to sample emotional, behavioral, physical and biochemical measures which might be sensitive to the changes of an effective stress management program.

  7. Biochemical processes of oligotrophic peat deposits of Vasyugan Mire

    NASA Astrophysics Data System (ADS)

    Inisheva, L. I.; Sergeeva, M. A.

    2009-04-01

    The problem of peat and mire ecosystems functioning and their rational use is the main problem of biosphere study. This problem also refers to forecasting of biosphere changes results which are global and anthropogenic. According to many scientists' research the portion of mires in earth carbon balance is about 15% of world's stock. The aim of this study is to investigate biochemical processes in oligotrophic deposits in North-eastern part of Vasyugan Mire. The investigations were made on the territory of scientific-research ground (56˚ 03´ and 56˚ 57´ NL, 82˚ 22´ and 82˚ 42´ EL). It is situated between two rivers Bakchar and Iksa (in outskirts of the village Polynyanka, Bakchar region, Tomsk oblast). Evolution of investigated mire massif began with the domination of eutrophic phytocenosis - Filicinae, then sedge. Later transfer into oligotrophic phase was accompanied by formation of meter high-moor peat deposit. The age of three-meter peat deposit reaches four thousand years. Biochemical processes of carbon cycle cover the whole peat deposit, but the process activity and its direction in different layers are defined by genesis and duration of peat formation. So, the number of cellulose-fermenting aerobes in researched peat deposits ranges from 16.8 to 75.5 million CFU/g, and anaerobic bacteria from 9.6 to 48.6 million CFU/g. The high number of aerobes is characteristic for high water levels, organizing by raised bog peats. Their number decreases along the profile in 1.7 - 2 times. The number of microflora in peat deposit is defined by the position in the landscape profile (different geneses), by the depth, by hydrothermic conditions of years and individual months. But microflora activity shows along all depth of peat deposit. We found the same in the process of studying of micromycete complex structure. There was revealed either active component micromycete complex - mycelium, or inert one - spores in a meter layer of peat deposit. If mushrooms

  8. Clinical-biochemical correlations in acromegaly at diagnosis and the real prevalence of biochemically discordant disease.

    PubMed

    Mercado, Moisés; Espinosa de los Monteros, Ana Laura; Sosa, Ernesto; Cheng, Sonia; Mendoza, Victoria; Hernández, Irma; Sandoval, Carolina; Guinto, Gerardo; Molina, Mario

    2004-01-01

    To analyze clinical-biochemical correlations in newly diagnosed acromegaly, focusing in particular on patients with discrepant parameters. Retrospective study. Data from 164 patients with acromegaly seen between 1995 and 2003. Patients were reviewed for the presence of headaches, arthralgias, hypertension, menstrual abnormalities, impotence, glucose intolerance or diabetes. Biochemical evaluation consisted of age- and gender-adjusted IGF-I levels and glucose-suppressed GH. Magnetic resonance imaging (MRI) revealed macroadenoma in 127 patients and microadenoma in 37. Patients with macroadenomas were younger than those with microadenomas and the disease was more frequent in females. Excluding acral enlargement, which was present in all the patients, the most commonly reported complaints were headaches (66%) and arthralgias (52%). Hypertension was present in 37% of patients, whereas the prevalence of glucose intolerance and diabetes was 27 and 32%, respectively. Hyperprolactinemia was present in 20% of patients with microadenomas and in 40% of patients with macroadenomas. Hypogonadism was demonstrated in more than half of the patients and was not related to tumor size or prolactin level. Of all the clinical and metabolic abnormalities of acromegaly, only the presence of diabetes correlated with both basal and nadir post-glucose GH levels. Only 4 patients (2.4%) had glucose-suppressed GH values of <1 ng/ml in the presence of clinical evidence of acromegaly, an elevated IGF-I level and a pituitary adenoma on MRI. Clinical features of acromegaly correlate poorly with indices of biochemical activity. The prevalence of biochemically discordant acromegaly is considerably lower than recently reported.

  9. Biochemical reaction engineering and process development in anaerobic wastewater treatment.

    PubMed

    Aivasidis, Alexander; Diamantis, Vasileios

    2005-01-01

    Developments in production technology have frequently resulted in the concentrated local accumulation of highly organic-laden wastewaters. Anaerobic wastewater treatment, in industrial applications, constitutes an advanced method of synthesis by which inexpensive substrates are converted into valuable disproportionate products. A critical discussion of certain fundamental principles of biochemical reaction engineering relevant to the anaerobic mode of operation is made here, with special emphasis on the roles of thermodynamics, kinetics, mass and heat transfer, reactor design, biomass retention and recycling. The applications of the anaerobic processes are discussed, introducing the principles of an upflow anaerobic sludge bed reactor and a fixed-bed loop reactor. The merits of staging reactor systems are presented using selected examples based on two decades of research in the field of anaerobic fermentation and wastewater treatment at the Forschungszentrum Julich (Julich Research Center, Germany). Wastewater treatment is an industrial process associated with one of the largest levels of mass throughput known, and for this reason it provides a major impetus to further developments in bioprocess technology in general.

  10. The need for combined inorganic, biochemical, and nutritional studies of chromium(III).

    PubMed

    Vincent, John B; Love, Sharifa T

    2012-09-01

    The history of biochemical and nutritional studies of the element is unfortunately full of twists and turns, most leading to dead ends. Chromium (Cr), as the trivalent ion, has been proposed to be an essential element, a body mass and muscle development agent, and, in the form of the most popular Cr-containing nutritional supplement, to be toxic when given orally to mammals. None of these proposals, despite significant attention in the popular media, has proven to be correct. Trivalent chromium has also been proposed as a therapeutic agent to increase insulin sensitivity and affect lipid metabolism, although a molecular mechanism for such actions has not been elucidated. Greater cooperative research interactions between nutritionists, biochemists, and chemists might have avoided the earlier issues in nutritional and biochemical Cr research and is necessary to establish the potential role of Cr as a therapeutic agent at a molecular level. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  11. Mechanism of Salinity Tolerance in Plants: Physiological, Biochemical, and Molecular Characterization

    PubMed Central

    Huang, Bingru

    2014-01-01

    Salinity is a major abiotic stress limiting growth and productivity of plants in many areas of the world due to increasing use of poor quality of water for irrigation and soil salinization. Plant adaptation or tolerance to salinity stress involves complex physiological traits, metabolic pathways, and molecular or gene networks. A comprehensive understanding on how plants respond to salinity stress at different levels and an integrated approach of combining molecular tools with physiological and biochemical techniques are imperative for the development of salt-tolerant varieties of plants in salt-affected areas. Recent research has identified various adaptive responses to salinity stress at molecular, cellular, metabolic, and physiological levels, although mechanisms underlying salinity tolerance are far from being completely understood. This paper provides a comprehensive review of major research advances on biochemical, physiological, and molecular mechanisms regulating plant adaptation and tolerance to salinity stress. PMID:24804192

  12. Scaling up Semi-Arid Grassland Biochemical Content from the Leaf to the Canopy Level: Challenges and Opportunities

    PubMed Central

    He, Yuhong; Mui, Amy

    2010-01-01

    Remote sensing imagery is being used intensively to estimate the biochemical content of vegetation (e.g., chlorophyll, nitrogen, and lignin) at the leaf level. As a result of our need for vegetation biochemical information and our increasing ability to obtain canopy spectral data, a few techniques have been explored to scale leaf-level biochemical content to the canopy level for forests and crops. However, due to the contribution of non-green materials (i.e., standing dead litter, rock, and bare soil) from canopy spectra in semi-arid grasslands, it is difficult to obtain information about grassland biochemical content from remote sensing data at the canopy level. This paper summarizes available methods used to scale biochemical information from the leaf level to the canopy level and groups these methods into three categories: direct extrapolation, canopy-integrated approach, and inversion of physical models. As for semi-arid heterogeneous grasslands, we conclude that all methods are useful, but none are ideal. It is recommended that future research should explore a systematic upscaling framework which combines spatial pattern analysis, canopy-integrated approach, and modeling methods to retrieve vegetation biochemical content at the canopy level. PMID:22163513

  13. Model-Based Design of Biochemical Microreactors.

    PubMed

    Elbinger, Tobias; Gahn, Markus; Neuss-Radu, Maria; Hante, Falk M; Voll, Lars M; Leugering, Günter; Knabner, Peter

    2016-01-01

    Mathematical modeling of biochemical pathways is an important resource in Synthetic Biology, as the predictive power of simulating synthetic pathways represents an important step in the design of synthetic metabolons. In this paper, we are concerned with the mathematical modeling, simulation, and optimization of metabolic processes in biochemical microreactors able to carry out enzymatic reactions and to exchange metabolites with their surrounding medium. The results of the reported modeling approach are incorporated in the design of the first microreactor prototypes that are under construction. These microreactors consist of compartments separated by membranes carrying specific transporters for the input of substrates and export of products. Inside the compartments of the reactor multienzyme complexes assembled on nano-beads by peptide adapters are used to carry out metabolic reactions. The spatially resolved mathematical model describing the ongoing processes consists of a system of diffusion equations together with boundary and initial conditions. The boundary conditions model the exchange of metabolites with the neighboring compartments and the reactions at the surface of the nano-beads carrying the multienzyme complexes. Efficient and accurate approaches for numerical simulation of the mathematical model and for optimal design of the microreactor are developed. As a proof-of-concept scenario, a synthetic pathway for the conversion of sucrose to glucose-6-phosphate (G6P) was chosen. In this context, the mathematical model is employed to compute the spatio-temporal distributions of the metabolite concentrations, as well as application relevant quantities like the outflow rate of G6P. These computations are performed for different scenarios, where the number of beads as well as their loading capacity are varied. The computed metabolite distributions show spatial patterns, which differ for different experimental arrangements. Furthermore, the total output of G6P

  14. Model-Based Design of Biochemical Microreactors

    PubMed Central

    Elbinger, Tobias; Gahn, Markus; Neuss-Radu, Maria; Hante, Falk M.; Voll, Lars M.; Leugering, Günter; Knabner, Peter

    2016-01-01

    Mathematical modeling of biochemical pathways is an important resource in Synthetic Biology, as the predictive power of simulating synthetic pathways represents an important step in the design of synthetic metabolons. In this paper, we are concerned with the mathematical modeling, simulation, and optimization of metabolic processes in biochemical microreactors able to carry out enzymatic reactions and to exchange metabolites with their surrounding medium. The results of the reported modeling approach are incorporated in the design of the first microreactor prototypes that are under construction. These microreactors consist of compartments separated by membranes carrying specific transporters for the input of substrates and export of products. Inside the compartments of the reactor multienzyme complexes assembled on nano-beads by peptide adapters are used to carry out metabolic reactions. The spatially resolved mathematical model describing the ongoing processes consists of a system of diffusion equations together with boundary and initial conditions. The boundary conditions model the exchange of metabolites with the neighboring compartments and the reactions at the surface of the nano-beads carrying the multienzyme complexes. Efficient and accurate approaches for numerical simulation of the mathematical model and for optimal design of the microreactor are developed. As a proof-of-concept scenario, a synthetic pathway for the conversion of sucrose to glucose-6-phosphate (G6P) was chosen. In this context, the mathematical model is employed to compute the spatio-temporal distributions of the metabolite concentrations, as well as application relevant quantities like the outflow rate of G6P. These computations are performed for different scenarios, where the number of beads as well as their loading capacity are varied. The computed metabolite distributions show spatial patterns, which differ for different experimental arrangements. Furthermore, the total output of G6P

  15. Biochemical fiber sensor based on evanescent field for detection persistent organic pollutants (POPs)

    NASA Astrophysics Data System (ADS)

    Prasetyo, Edi; Putri Gitrin, Martia; Marzuki, Ahmad; Suryanti, Venty

    2017-01-01

    Fiber optic is a light waveguides media that are cylindrical. Optical fiber has certain properties when it transmits light so it can be developed to be a sensing device or sensor. Evanescent wave phenomena appear when there are total internal reflections from many modes in an optical fiber. In this research, the Biochemical Fiber Sensor (BFS) using polishing cladding and some of the core fiber will be fabricated. BFS is used to interact with a biochemical compound. The principle of BFS is based on evanescent absorption which absorbs the typical spectrum of a biochemical compound. By measuring the spectrum from the light output in the BFS, evanescent absorption spectra can be analyzed an optical fiber. In this study, the biochemical compounds that used are lindane that is one of the Persistent Organic Pollutants (POPs). The result showed that there is a change from BFS spectra when it was exposed by POPs compound with various concentration. That change showed that there is evanescent absorption in BFS. Concentration of POPs compound is proportional with evanescent absorption of the POPs compound.

  16. Physiological, Biochemical, and Molecular Mechanisms of Heat Stress Tolerance in Plants

    PubMed Central

    Hasanuzzaman, Mirza; Nahar, Kamrun; Alam, Md. Mahabub; Roychowdhury, Rajib; Fujita, Masayuki

    2013-01-01

    High temperature (HT) stress is a major environmental stress that limits plant growth, metabolism, and productivity worldwide. Plant growth and development involve numerous biochemical reactions that are sensitive to temperature. Plant responses to HT vary with the degree and duration of HT and the plant type. HT is now a major concern for crop production and approaches for sustaining high yields of crop plants under HT stress are important agricultural goals. Plants possess a number of adaptive, avoidance, or acclimation mechanisms to cope with HT situations. In addition, major tolerance mechanisms that employ ion transporters, proteins, osmoprotectants, antioxidants, and other factors involved in signaling cascades and transcriptional control are activated to offset stress-induced biochemical and physiological alterations. Plant survival under HT stress depends on the ability to perceive the HT stimulus, generate and transmit the signal, and initiate appropriate physiological and biochemical changes. HT-induced gene expression and metabolite synthesis also substantially improve tolerance. The physiological and biochemical responses to heat stress are active research areas, and the molecular approaches are being adopted for developing HT tolerance in plants. This article reviews the recent findings on responses, adaptation, and tolerance to HT at the cellular, organellar, and whole plant levels and describes various approaches being taken to enhance thermotolerance in plants. PMID:23644891

  17. Biochemical monitoring in fenugreek to develop functional food and medicinal plant variants.

    PubMed

    Thomas, James E; Bandara, Manjula; Lee, Ee Lynn; Driedger, Darcy; Acharya, Surya

    2011-02-28

    Many plants used as functional foods or for medicinal purposes have been criticized for their inconsistent physiological effects. Variation in genotype and environmental conditions under which plants are produced can contribute to this inconsistency in biochemical composition. Fenugreek (Trigonella foenum-graecum L.) is a medicinal plant that not only can lower blood glucose and cholesterol levels in animals, but also can be used as a forage crop for livestock feed. Seed content for the bioactive compounds diosgenin, galactomannan and 4-hydroxyisoleucine was characterized for ten fenugreek genotypes under rainfed and irrigated conditions. High and low seed yielding genotype/environment combinations were identified that possessed distinct biochemical and seed production traits. In general high seed yielding genotype/environment combinations exhibited a more stable biochemical composition and consisted largely of irrigated fenugreek. This research indicates that comprehensive biochemical analysis of plant products would facilitate the development of more reliable produce for use by the functional food/medicinal plant industry. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Biochemical processing of geothermal brines and sludges: Adaptability to multiple industrial applications

    SciTech Connect

    Premuzic, E.T.; Lin, M.S.; Jin, J.Z.

    1994-07-01

    Extensive Research and Development effort leading to the identification of low cost environmentally acceptable disposal of geothermal brines and sludges has shown that biochemical processing of the waste streams meets these requirements. Further exploration of the process variables has also indicated that biochemical treatment of waste streams is a versatile technology, adaptable to several applications beyond that of rendering hazardous and/or mixed wastes to nonhazardous byproducts which meet regulatory requirements. Such advanced biochemical technologies may be used for solubilization and recovery of a few metals such as arsenic and mercury to the isolation of many metals, including radionuclides. Spin-offs from this technology have also applications in the treatment of crude oils, oil wastes and the recovery of valuable metals and salts. In the metal recovery mode the aqueous phase can be reinjected or treated further so that the end products meet the environmental drinking water standards. In this paper, recent studies dealing with the multiple industrial applications potential of biochemical processes will be discussed.

  19. Optical tweezers and multiphoton microscopies integrated photonic tool for mechanical and biochemical cell processes studies

    NASA Astrophysics Data System (ADS)

    de Thomaz, A. A.; Faustino, W. M.; Fontes, A.; Fernandes, H. P.; Barjas-Castro, M. d. L.; Metze, K.; Giorgio, S.; Barbosa, L. C.; Cesar, C. L.

    2007-09-01

    The research in biomedical photonics is clearly evolving in the direction of the understanding of biological processes at the cell level. The spatial resolution to accomplish this task practically requires photonics tools. However, an integration of different photonic tools and a multimodal and functional approach will be necessary to access the mechanical and biochemical cell processes. This way we can observe mechanicaly triggered biochemical events or biochemicaly triggered mechanical events, or even observe simultaneously mechanical and biochemical events triggered by other means, e.g. electricaly. One great advantage of the photonic tools is its easiness for integration. Therefore, we developed such integrated tool by incorporating single and double Optical Tweezers with Confocal Single and Multiphoton Microscopies. This system can perform 2-photon excited fluorescence and Second Harmonic Generation microscopies together with optical manipulations. It also can acquire Fluorescence and SHG spectra of specific spots. Force, elasticity and viscosity measurements of stretched membranes can be followed by real time confocal microscopies. Also opticaly trapped living protozoas, such as leishmania amazonensis. Integration with CARS microscopy is under way. We will show several examples of the use of such integrated instrument and its potential to observe mechanical and biochemical processes at cell level.

  20. Developments in commercially produced microbials at Biochem Products

    Treesearch

    John Lublinkhof; Douglas H. Ross

    1985-01-01

    Biochem Products is part of a large industrial and scientific family - the Solvay Group. Solvay, headquartered in Brussels, Belgium is a multinational company with 46,000 employees worldwide. In the U.S., our working partners include a large polymer manufacturer, a peroxygen producer and a leading poultry and animal health products company. Biochem Products is a...

  1. A Biochemical Approach to the Problem of Dyslexia.

    ERIC Educational Resources Information Center

    Baker, Sidney McDonald

    1985-01-01

    The paper presents the case of a sixth-grade boy, labeled dyslexic, who responded positively to a biochemical approach. Remedy of iron, zinc, and Vitamin B-6 deficiencies as well as an imbalance of fatty acids resulted in improvements in hair and skin and also in reading. A biochemical approach to behavior problems is proposed. (Author/CL)

  2. A Biochemical Approach to the Problem of Dyslexia.

    ERIC Educational Resources Information Center

    Baker, Sidney McDonald

    1985-01-01

    The paper presents the case of a sixth-grade boy, labeled dyslexic, who responded positively to a biochemical approach. Remedy of iron, zinc, and Vitamin B-6 deficiencies as well as an imbalance of fatty acids resulted in improvements in hair and skin and also in reading. A biochemical approach to behavior problems is proposed. (Author/CL)

  3. [On the quality control in forensic biochemical departments].

    PubMed

    Tuchik, E S; Astashkina, O G

    2013-01-01

    The main principles of quality control in the laboratory practice of forensic biochemical departments are discussed. Recommendations on international standardization are suggested. Characteristics of the main phases of intralaboratory quality control of investigations and the reagents used in them are described. The necessity of quality control at all stages of forensic-biochemical studies and expertise is emphasized.

  4. Alternative aircraft anti-icing formulations with reduced aquatic toxicity and biochemical oxygen demand

    USGS Publications Warehouse

    Gold, Harris; Joback, Kevin; Geis, Steven; Bowman, George; Mericas, Dean; Corsi, Steven R.; Ferguson, Lee

    2010-01-01

    The current research was conducted to identify alternative aircraft and pavement deicer and anti-icer formulations with improved environmental characteristics compared to currently used commercial products (2007). The environmental characteristics of primary concern are the biochemical oxygen demand (BOD) and aquatic toxicity of the fully formulated products. Except when the distinction among products is necessary for clarity, “deicer” will refer to aircraft-deicing fluids (ADFs), aircraft anti-icing fluids (AAFs), and pavementdeicing materials (PDMs).

  5. Applied spectrophotometry: analysis of a biochemical mixture.

    PubMed

    Trumbo, Toni A; Schultz, Emeric; Borland, Michael G; Pugh, Michael Eugene

    2013-01-01

    Spectrophotometric analysis is essential for determining biomolecule concentration of a solution and is employed ubiquitously in biochemistry and molecular biology. The application of the Beer-Lambert-Bouguer Lawis routinely used to determine the concentration of DNA, RNA or protein. There is however a significant difference in determining the concentration of a given species (RNA, DNA, protein) in isolation (a contrived circumstance) as opposed to determining that concentration in the presence of other species (a more realistic situation). To present the student with a more realistic laboratory experience and also to fill a hole that we believe exists in student experience prior to reaching a biochemistry course, we have devised a three week laboratory experience designed so that students learn to: connect laboratory practice with theory, apply the Beer-Lambert-Bougert Law to biochemical analyses, demonstrate the utility and limitations of example quantitative colorimetric assays, demonstrate the utility and limitations of UV analyses for biomolecules, develop strategies for analysis of a solution of unknown biomolecular composition, use digital micropipettors to make accurate and precise measurements, and apply graphing software. Copyright © 2013 Wiley Periodicals, Inc.

  6. Multiple capillary biochemical analyzer with barrier member

    DOEpatents

    Dovichi, N.J.; Zhang, J.Z.

    1996-10-22

    A multiple capillary biochemical analyzer is disclosed for sequencing DNA and performing other analyses, in which a set of capillaries extends from wells in a microtiter plate into a cuvette. In the cuvette the capillaries are held on fixed closely spaced centers by passing through a sandwich construction having a pair of metal shims which squeeze between them a rubber gasket, forming a leak proof seal for an interior chamber in which the capillary ends are positioned. Sheath fluid enters the chamber and entrains filament sample streams from the capillaries. The filament sample streams, and sheath fluid, flow through aligned holes in a barrier member spaced close to the capillary ends, into a collection chamber having a lower glass window. The filament streams are illuminated above the barrier member by a laser, causing them to fluoresce. The fluorescence is viewed end-on by a CCD camera chip located below the glass window. The arrangement ensures an equal optical path length from all fluorescing spots to the CCD chip and also blocks scattered fluorescence illumination, providing more uniform results and an improved signal-to-noise ratio. 12 figs.

  7. A biochemically structured model for Saccharomyces cerevisiae.

    PubMed

    Lei, F; Rotbøll, M; Jørgensen, S B

    2001-07-12

    A biochemically structured model for the aerobic growth of Saccharomyces cerevisiae on glucose and ethanol is presented. The model focuses on the pyruvate and acetaldehyde branch points where overflow metabolism occurs when the growth changes from oxidative to oxido-reductive. The model is designed to describe the onset of aerobic alcoholic fermentation during steady-state as well as under dynamical conditions, by triggering an increase in the glycolytic flux using a key signalling component which is assumed to be closely related to acetaldehyde. An investigation of the modelled process dynamics in a continuous cultivation revealed multiple steady states in a region of dilution rates around the transition between oxidative and oxido-reductive growth. A bifurcation analysis using the two external variables, the dilution rate, D, and the inlet concentration of glucose, S(f), as parameters, showed that a fold bifurcation occurs close to the critical dilution rate resulting in multiple steady-states. The region of dilution rates within which multiple steady states may occur depends strongly on the substrate feed concentration. Consequently a single steady state may prevail at low feed concentrations, whereas multiple steady states may occur over a relatively wide range of dilution rates at higher feed concentrations.

  8. Biochemical Testing After Pheochromocytoma Removal: How Early?

    PubMed

    Zelinka, T; Petrák, O; Hamplová, B; Turková, H; Waldauf, P; Rosa, J; Šomlóová, Z; Holaj, R; Štrauch, B; Indra, T; Kršek, M; Brabcová Vránková, A; Vránková, A Brabcová; Musil, Z; Dušková, J; Kubinyi, J; Michalský, D; Novák, K; Widimský, J

    2015-08-01

    Pheochromocytomas are catecholamine-producing tumors with typical clinical presentation. Tumor resection is considered as an appropriate treatment strategy. Due to its unpredictable clinical behavior, biochemical testing is mandatory to confirm the success of tumor removal after surgery. The aim of the study was to investigate the feasibility of a shorter interval of postoperative testing (earlier than the recommended 2-4 weeks according to recently published Guidelines). We investigated 81 patients with pheochromocytoma before and after surgery. Postoperative examination was performed of stable subjects after their transport from the surgical to the internal ward (7.1±2.2 days after surgery). Plasma metanephrines were used for the diagnosis of pheochromocytoma and confirmation of successful tumor removal. All subjects with pheochromocytoma had markedly elevated plasma metanephrines before surgery. No correlation between postoperative interval (the shortest being 3 days) and plasma metanephrine levels was found. Postoperative plasma metanephrine levels did not differ significantly from those taken at the one-year follow-up. In conclusion, we have shown that early postoperative diagnostic workup of subjects with pheochromocytoma is possible and may thus simplify early postoperative management of this clinical condition. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Multiple capillary biochemical analyzer with barrier member

    DOEpatents

    Dovichi, Norman J.; Zhang, Jian Z.

    1996-01-01

    A multiple capillary biochemical analyzer for sequencing DNA and performing other analyses, in which a set of capillaries extends from wells in a microtiter plate into a cuvette. In the cuvette the capillaries are held on fixed closely spaced centers by passing through a sandwich construction having a pair of metal shims which squeeze between them a rubber gasket, forming a leak proof seal for an interior chamber in which the capillary ends are positioned. Sheath fluid enters the chamber and entrains filament sample streams from the capillaries. The filament sample streams, and sheath fluid, flow through aligned holes in a barrier member spaced close to the capillary ends, into a collection chamber having a lower glass window. The filament streams are illuminated above the barrier member by a laser, causing them to fluoresce. The fluorescence is viewed end-on by a CCD camera chip located below the glass window. The arrangement ensures an equal optical path length from all fluorescing spots to the CCD chip and also blocks scattered fluorescence illumination, providing more uniform results and an improved signal to noise ratio.

  10. Induced biochemical interactions in crude oils

    SciTech Connect

    Premuzic, E.T.; Lin, M.S.

    1996-08-01

    In the evolution of oil from sedimentary to reservoir conditions, the hydrogen to carbon ratios decrease while the oxygen, nitrogen, and sulfur to carbon ratios increase. During this process, the oils become heavier and richer in asphaltenes. In terms of chemical composition, the oils become enriched in resins, asphaltenes, and polar compounds containing the heteroatoms and metals. Over the geological periods of time, the chemical and physical changes have been brought about by chemical, biological (biochemical) and physical (temperature and pressure) means as well as by the catalytic effects of the sedimentary matrices, migration, flooding, and other physical processes. Therefore, different types of oils are the end products of a given set of such interactions which were brought about by multiple and simultaneous physicochemical processes involving electron transfer, free radical, and chemical reactions. A biocatalyst introduced into a reaction mixture of the type produced by such reactions will seek available chemical reaction sites and react at the most favorable ones. The rates and the chemical pathways by which the biocatalytic reactions will proceed will depend on the oil type and the biocatalyst(s). Some of the possible reaction pathways that may occur in such complex mixtures are discussed.

  11. [Biochemical tests for identifying Pasteurella multocida].

    PubMed

    Karaivanov, L

    1984-01-01

    Studied was the biochemical activity of a total of 168 strains of Pasteurella--73 isolated from birds (48 from cases of acute fowl cholera, and 25--of chronic cholera), and 95 isolated from mammals (3 from lambs, 24 from pigs, 36 from cattle, and 32 from rabbits) with regard to the tests determining the hemolytic activity, production of indol, reduction of nitrates, breakdown of urea, beta galactosidase activity, production of hydrogen sulfide, ornitin-, arginine-, lysine-decarboxylase-, and phosphatase activity, and the fermentation of substrates such as manite, glucose, galactose, saccharose, manose, levulose, dulcite, lactose, maltose, rafinose, trechalose, salicin, melobiose, icelobiose, arabinose, xylose, and sorbite. To differentiate Pasteurella multocida strains isolated from mamals from those isolated from birds the phosphatase activity test on solid media with sodium phenolphtalein diphosphate had to be employed Pasteurella organisms isolated from mammals showed positive phosphatase activity, while those isolated from birds exhibited a negative one. Arabinose and xylose fermentation tests could simultaneously be used. Pasteurellae isolated in cases of acute fowl cholera showed positive reaction for arabinose and a negative one for xylose, while the strains isolated from mammals showed the reverse activity. The strains isolated in cases of chronic fowl cholera were shown to belong to this group.

  12. BIOCHEMICAL ANALYSIS OF PKR ACTIVATION BY PACT†

    PubMed Central

    Peters, Gregory A.; Dickerman, Benjamin; Sen, Ganes C.

    2009-01-01

    Many extracellular stresses cause inhibition of translation initiation by triggering phosphorylation of the initiation factor, eIF-2α. A major protein kinase responsible for this phosphorylation is PKR, a latent kinase which itself needs activation by autophosphorylation. In stressed cells, this activation occurs when PACT, a PKR-binding protein, is phosphorylated and activates PKR. We have previously demonstrated that the presence of specific residues in domain 3 of PACT is necessary for its ability to activate PKR in vivo. Here, we analyzed the biochemical properties of the inactive PACT mutants by assessing their ability to bind and activate PKR in vitro. Among the essential residues, two serines need to be phosphorylated in vivo for PACT’s ability to activate PKR. We substituted those serines with aspartic acids, mimics of phosphoserines, and investigated the properties of the corresponding mutant PACTs. In vitro, they activate PKR more efficiently because they bind to PKR more tightly. These results indicate that stress-induced phosphorylation of specific serine residues in domain 3 of PACT increases its affinity for PKR, which leads to better activation of PKR and resultant eIF-2α phosphorylation. PMID:19580324

  13. Biochemical and Genetic Insights into Asukamycin Biosynthesis*

    PubMed Central

    Rui, Zhe; Petříčková, Kateřina; Škanta, František; Pospíšil, Stanislav; Yang, Yanling; Chen, Chung-Yung; Tsai, Shih-Feng; Floss, Heinz G.; Petříček, Miroslav; Yu, Tin-Wein

    2010-01-01

    Asukamycin, a member of the manumycin family metabolites, is an antimicrobial and potential antitumor agent isolated from Streptomyces nodosus subsp. asukaensis. The entire asukamycin biosynthetic gene cluster was cloned, assembled, and expressed heterologously in Streptomyces lividans. Bioinformatic analysis and mutagenesis studies elucidated the biosynthetic pathway at the genetic and biochemical level. Four gene sets, asuA–D, govern the formation and assembly of the asukamycin building blocks: a 3-amino-4-hydroxybenzoic acid core component, a cyclohexane ring, two triene polyketide chains, and a 2-amino-3-hydroxycyclopent-2-enone moiety to form the intermediate protoasukamycin. AsuE1 and AsuE2 catalyze the conversion of protoasukamycin to 4-hydroxyprotoasukamycin, which is epoxidized at C5–C6 by AsuE3 to the final product, asukamycin. Branched acyl CoA starter units, derived from Val, Leu, and Ile, can be incorporated by the actions of the polyketide synthase III (KSIII) AsuC3/C4 as well as the cellular fatty acid synthase FabH to produce the asukamycin congeners A2–A7. In addition, the type II thioesterase AsuC15 limits the cellular level of ω-cyclohexyl fatty acids and likely maintains homeostasis of the cellular membrane. PMID:20522559

  14. Robustness analysis of stochastic biochemical systems.

    PubMed

    Ceska, Milan; Safránek, David; Dražan, Sven; Brim, Luboš

    2014-01-01

    We propose a new framework for rigorous robustness analysis of stochastic biochemical systems that is based on probabilistic model checking techniques. We adapt the general definition of robustness introduced by Kitano to the class of stochastic systems modelled as continuous time Markov Chains in order to extensively analyse and compare robustness of biological models with uncertain parameters. The framework utilises novel computational methods that enable to effectively evaluate the robustness of models with respect to quantitative temporal properties and parameters such as reaction rate constants and initial conditions. We have applied the framework to gene regulation as an example of a central biological mechanism where intrinsic and extrinsic stochasticity plays crucial role due to low numbers of DNA and RNA molecules. Using our methods we have obtained a comprehensive and precise analysis of stochastic dynamics under parameter uncertainty. Furthermore, we apply our framework to compare several variants of two-component signalling networks from the perspective of robustness with respect to intrinsic noise caused by low populations of signalling components. We have successfully extended previous studies performed on deterministic models (ODE) and showed that stochasticity may significantly affect obtained predictions. Our case studies demonstrate that the framework can provide deeper insight into the role of key parameters in maintaining the system functionality and thus it significantly contributes to formal methods in computational systems biology.

  15. Analysis of Homeostatic Mechanisms in Biochemical Networks.

    PubMed

    Reed, Michael; Best, Janet; Golubitsky, Martin; Stewart, Ian; Nijhout, H Frederik

    2017-09-07

    Cell metabolism is an extremely complicated dynamical system that maintains important cellular functions despite large changes in inputs. This "homeostasis" does not mean that the dynamical system is rigid and fixed. Typically, large changes in external variables cause large changes in some internal variables so that, through various regulatory mechanisms, certain other internal variables (concentrations or velocities) remain approximately constant over a finite range of inputs. Outside that range, the mechanisms cease to function and concentrations change rapidly with changes in inputs. In this paper we analyze four different common biochemical homeostatic mechanisms: feedforward excitation, feedback inhibition, kinetic homeostasis, and parallel inhibition. We show that all four mechanisms can occur in a single biological network, using folate and methionine metabolism as an example. Golubitsky and Stewart have proposed a method to find homeostatic nodes in networks. We show that their method works for two of these mechanisms but not the other two. We discuss the many interesting mathematical and biological questions that emerge from this analysis, and we explain why understanding homeostatic control is crucial for precision medicine.

  16. [Cystinuria update: clinical, biochemical and genetic aspects].

    PubMed

    Orts Costa, J A; Zúñiga Cabrera, A; Martínez de la Cára y Salmerón, J

    2003-06-01

    Cystinuria is an autosomal recessive disorder with an estimated incidence of 1 case in 7000 live births, that results in elevated urinary excretion of cystine and dibasic aminoacids: ornithine, lysine and arginine. Discussed by Sir Archibald Edward Garrod, in 1908, as one of the four first known inborn errors of metabolism, it is characterized by a defect in transport of cystine and dibasic aminoacids, that affects their reabsortion in both renal tubule and gastrointestinal tract. To date, according to the recent molecular findings, two genes have been identified as responsible for this disease: SLC3A1 and SLC7A9. A more accurate pheno/genotyping identification of cystinuric patients will allow to improve prophilaxis and therapy for this illness. Cystinuria only causes recurrent urolithiasis (about 1-2 / of renal calculi in adults) and its associated complications as clinical feature because of poor cystine solubility at low pH. An accurate control over prohylaxis (based on high water intake and potassium citrate treatment, on first line, and tiol-derivatives treatment, on second line) must be taken in patients -like homozygous type I- with high lithiasis risk. However, approximately one half of patients under prophylaxis control will develop recurrent lithiasis; in this case, only urology or surgical approaches would be possible. 474 Updated knowledge about biochemical, genetic, clinical, diagnosis, prevention, treatment and prognosis aspects of this, relatively unusual, disease has been reviewed in this article.

  17. Biochemical indicators of hepatotoxic effects of pesticides.

    PubMed

    Dahamna, S; Sekfali, N; Walker, C H

    2004-01-01

    Pesticides can cause damage to man and beneficial organisms. Some sub-lethal effects of pesticides were studied in birds with a view to identifying characteristic biochemical responses that may be useful for the monitoring of exposure to sub-lethal levels in the field. Pesticides were used: demeton-S-methyl, (DSM), chlorpyriphos, chlorfenviphos, triazophos, pirimicarb, methiocarb and permethrin. Blood was collected before dosing, and 2, 6, 24, 48 and 72 hours after the treatment from the brachial vein of birds. Enzyme activities were assayed in the plasma or serum samples obtained. The assays used were GOT, MDH, GDH, SDH, GAMMA GT and ChE. The results showed an increase in plasma and serum GOT and gamma-GT levels were found in all animals treated with the previous pesticides. The level of ChE increased in birds after treatment with permethrin. It was concluded that the pesticides cause structural and functional changes in the liver and also, the measurement of the previous parameter activities may be useful for assessing exposure and sub-lethal effects of pesticides on the wildlife.

  18. Robustness Analysis of Stochastic Biochemical Systems

    PubMed Central

    Česka, Milan; Šafránek, David; Dražan, Sven; Brim, Luboš

    2014-01-01

    We propose a new framework for rigorous robustness analysis of stochastic biochemical systems that is based on probabilistic model checking techniques. We adapt the general definition of robustness introduced by Kitano to the class of stochastic systems modelled as continuous time Markov Chains in order to extensively analyse and compare robustness of biological models with uncertain parameters. The framework utilises novel computational methods that enable to effectively evaluate the robustness of models with respect to quantitative temporal properties and parameters such as reaction rate constants and initial conditions. We have applied the framework to gene regulation as an example of a central biological mechanism where intrinsic and extrinsic stochasticity plays crucial role due to low numbers of DNA and RNA molecules. Using our methods we have obtained a comprehensive and precise analysis of stochastic dynamics under parameter uncertainty. Furthermore, we apply our framework to compare several variants of two-component signalling networks from the perspective of robustness with respect to intrinsic noise caused by low populations of signalling components. We have successfully extended previous studies performed on deterministic models (ODE) and showed that stochasticity may significantly affect obtained predictions. Our case studies demonstrate that the framework can provide deeper insight into the role of key parameters in maintaining the system functionality and thus it significantly contributes to formal methods in computational systems biology. PMID:24751941

  19. Saturated fat intake predicts biochemical failure after prostatectomy.

    PubMed

    Strom, Sara S; Yamamura, Yuko; Forman, Michele R; Pettaway, Curtis A; Barrera, Stephanie L; DiGiovanni, John

    2008-06-01

    Previous reports show that obesity predicts biochemical failure after treatment for localized prostate cancer. Since obesity is associated with increased fat consumption, we investigated the role that dietary fat intake plays in modulating obesity-related risk of biochemical failure. We evaluated the association between saturated fat intake and biochemical failure among 390 men from a previously described prostatectomy cohort. Participants completed a food frequency questionnaire collecting nutrient information for the year prior to diagnosis. Because fat and energy intake are highly correlated, the residual method was used to adjust fat (total and saturated) intakes for energy. Biochemical-failure-free-survival rates were calculated using the Kaplan-Meier method. Crude and adjusted effects were estimated using Cox proportional hazards models. During a mean follow-up of 70.6 months, 78 men experienced biochemical failure. Men who consumed high- saturated fat (HSF) diets were more likely to experience biochemical failure (p = 0.006) and had significantly shorter biochemical-failure-free-survival than men with low saturated fat (LSF) diets (26.6 vs. 44.7 months, respectively, p = 0.002). After adjusting for obesity and clinical variables, HSF-diet patients were almost twice as likely to experience biochemical failure (hazard ratio = 1.95, p = 0.008) compared to LSF diet patients. Men who were both obese and consumed HSF diets had the shortest biochemical-failure-free-survival (19 months), and nonobese men who consumed LSF diets had the longest biochemical-failure-free-survival (46 months, p < 0.001). Understanding the interplay between modifiable factors, such as diet and obesity, and disease characteristics may lead to the development of behavioral and/or targeted interventions for patients at increased risk of progression. (c) 2008 Wiley-Liss, Inc.

  20. biochem4j: Integrated and extensible biochemical knowledge through graph databases.

    PubMed

    Swainston, Neil; Batista-Navarro, Riza; Carbonell, Pablo; Dobson, Paul D; Dunstan, Mark; Jervis, Adrian J; Vinaixa, Maria; Williams, Alan R; Ananiadou, Sophia; Faulon, Jean-Loup; Mendes, Pedro; Kell, Douglas B; Scrutton, Nigel S; Breitling, Rainer

    2017-01-01

    Biologists and biochemists have at their disposal a number of excellent, publicly available data resources such as UniProt, KEGG, and NCBI Taxonomy, which catalogue biological entities. Despite the usefulness of these resources, they remain fundamentally unconnected. While links may appear between entries across these databases, users are typically only able to follow such links by manual browsing or through specialised workflows. Although many of the resources provide web-service interfaces for computational access, performing federated queries across databases remains a non-trivial but essential activity in interdisciplinary systems and synthetic biology programmes. What is needed are integrated repositories to catalogue both biological entities and-crucially-the relationships between them. Such a resource should be extensible, such that newly discovered relationships-for example, those between novel, synthetic enzymes and non-natural products-can be added over time. With the introduction of graph databases, the barrier to the rapid generation, extension and querying of such a resource has been lowered considerably. With a particular focus on metabolic engineering as an illustrative application domain, biochem4j, freely available at http://biochem4j.org, is introduced to provide an integrated, queryable database that warehouses chemical, reaction, enzyme and taxonomic data from a range of reliable resources. The biochem4j framework establishes a starting point for the flexible integration and exploitation of an ever-wider range of biological data sources, from public databases to laboratory-specific experimental datasets, for the benefit of systems biologists, biosystems engineers and the wider community of molecular biologists and biological chemists.

  1. In Situ Biospectroscopic Investigation of Rapid Ischemic and Postmortem Induced Biochemical Alterations in the Rat Brain

    PubMed Central

    2015-01-01

    Rapid advances in imaging technologies have pushed novel spectroscopic modalities such as Fourier transform infrared spectroscopy (FTIR) and X-ray absorption spectroscopy (XAS) at the sulfur K-edge to the forefront of direct in situ investigation of brain biochemistry. However, few studies have examined the extent to which sample preparation artifacts confound results. Previous investigations using traditional analyses, such as tissue dissection, homogenization, and biochemical assay, conducted extensive research to identify biochemical alterations that occur ex vivo during sample preparation. In particular, altered metabolism and oxidative stress may be caused by animal death. These processes were a concern for studies using biochemical assays, and protocols were developed to minimize their occurrence. In this investigation, a similar approach was taken to identify the biochemical alterations that are detectable by two in situ spectroscopic methods (FTIR, XAS) that occur as a consequence of ischemic conditions created during humane animal killing. FTIR and XAS are well suited to study markers of altered metabolism such as lactate and creatine (FTIR) and markers of oxidative stress such as aggregated proteins (FTIR) and altered thiol redox (XAS). The results are in accordance with previous investigations using biochemical assays and demonstrate that the time between animal death and tissue dissection results in ischemic conditions that alter brain metabolism and initiate oxidative stress. Therefore, future in situ biospectroscopic investigations utilizing FTIR and XAS must take into consideration that brain tissue dissected from a healthy animal does not truly reflect the in vivo condition, but rather reflects a state of mild ischemia. If studies require the levels of metabolites (lactate, creatine) and markers of oxidative stress (thiol redox) to be preserved as close as possible to the in vivo condition, then rapid freezing of brain tissue via decapitation into

  2. Improved prediction of biochemical recurrence after radical prostatectomy by genetic polymorphisms.

    PubMed

    Morote, Juan; Del Amo, Jokin; Borque, Angel; Ars, Elisabet; Hernández, Carlos; Herranz, Felipe; Arruza, Antonio; Llarena, Roberto; Planas, Jacques; Viso, María J; Palou, Joan; Raventós, Carles X; Tejedor, Diego; Artieda, Marta; Simón, Laureano; Martínez, Antonio; Rioja, Luis A

    2010-08-01

    Single nucleotide polymorphisms are inherited genetic variations that can predispose or protect individuals against clinical events. We hypothesized that single nucleotide polymorphism profiling may improve the prediction of biochemical recurrence after radical prostatectomy. We performed a retrospective, multi-institutional study of 703 patients treated with radical prostatectomy for clinically localized prostate cancer who had at least 5 years of followup after surgery. All patients were genotyped for 83 prostate cancer related single nucleotide polymorphisms using a low density oligonucleotide microarray. Baseline clinicopathological variables and single nucleotide polymorphisms were analyzed to predict biochemical recurrence within 5 years using stepwise logistic regression. Discrimination was measured by ROC curve AUC, specificity, sensitivity, predictive values, net reclassification improvement and integrated discrimination index. The overall biochemical recurrence rate was 35%. The model with the best fit combined 8 covariates, including the 5 clinicopathological variables prostate specific antigen, Gleason score, pathological stage, lymph node involvement and margin status, and 3 single nucleotide polymorphisms at the KLK2, SULT1A1 and TLR4 genes. Model predictive power was defined by 80% positive predictive value, 74% negative predictive value and an AUC of 0.78. The model based on clinicopathological variables plus single nucleotide polymorphisms showed significant improvement over the model without single nucleotide polymorphisms, as indicated by 23.3% net reclassification improvement (p = 0.003), integrated discrimination index (p <0.001) and likelihood ratio test (p <0.001). Internal validation proved model robustness (bootstrap corrected AUC 0.78, range 0.74 to 0.82). The calibration plot showed close agreement between biochemical recurrence observed and predicted probabilities. Predicting biochemical recurrence after radical prostatectomy based on

  3. Validation of artificial neural network models for predicting biochemical markers associated with male infertility.

    PubMed

    Vickram, A S; Kamini, A Rao; Das, Raja; Pathy, M Ramesh; Parameswari, R; Archana, K; Sridharan, T B

    2016-08-01

    Seminal fluid is the secretion from many glands comprised of several organic and inorganic compounds including free amino acids, proteins, fructose, glucosidase, zinc, and other scavenging elements like Mg(2+), Ca(2+), K(+), and Na(+). Therefore, in the view of development of novel approaches and proper diagnosis to male infertility, overall understanding of the biochemical and molecular composition and its role in regulation of sperm quality is highly desirable. Perhaps this can be achieved through artificial intelligence. This study was aimed to elucidate and predict various biochemical markers present in human seminal plasma with three different neural network models. A total of 177 semen samples were collected for this research (both fertile and infertile samples) and immediately processed to prepare a semen analysis report, based on the protocol of the World Health Organization (WHO [2010]). The semen samples were then categorized into oligoasthenospermia (n=35), asthenospermia (n=35), azoospermia (n=22), normospermia (n=34), oligospermia (n=34), and control (n=17). The major biochemical parameters like total protein content, fructose, glucosidase, and zinc content were elucidated by standard protocols. All the biochemical markers were predicted by using three different artificial neural network (ANN) models with semen parameters as inputs. Of the three models, the back propagation neural network model (BPNN) yielded the best results with mean absolute error 0.025, -0.080, 0.166, and -0.057 for protein, fructose, glucosidase, and zinc, respectively. This suggests that BPNN can be used to predict biochemical parameters for the proper diagnosis of male infertility in assisted reproductive technology (ART) centres. AAS: absorption spectroscopy; AI: artificial intelligence; ANN: artificial neural networks; ART: assisted reproductive technology; BPNN: back propagation neural network model; DT: decision tress; MLP: multilayer perceptron; PESA: percutaneous

  4. Mechanical and biochemical mapping of human auricular cartilage for reliable assessment of tissue-engineered constructs.

    PubMed

    Nimeskern, Luc; Pleumeekers, Mieke M; Pawson, Duncan J; Koevoet, Wendy L M; Lehtoviita, Iina; Soyka, Michael B; Röösli, Christof; Holzmann, David; van Osch, Gerjo J V M; Müller, Ralph; Stok, Kathryn S

    2015-07-16

    It is key for successful auricular (AUR) cartilage tissue-engineering (TE) to ensure that the engineered cartilage mimics the mechanics of the native tissue. This study provides a spatial map of the mechanical and biochemical properties of human auricular cartilage, thus establishing a benchmark for the evaluation of functional competency in AUR cartilage TE. Stress-relaxation indentation (instantaneous modulus, Ein; maximum stress, σmax; equilibrium modulus, Eeq; relaxation half-life time, t1/2; thickness, h) and biochemical parameters (content of DNA; sulfated-glycosaminoglycan, sGAG; hydroxyproline, HYP; elastin, ELN) of fresh human AUR cartilage were evaluated. Samples were categorized into age groups and according to their harvesting region in the human auricle (for AUR cartilage only). AUR cartilage displayed significantly lower Ein, σmax, Eeq, sGAG content; and significantly higher t1/2, and DNA content than NAS cartilage. Large amounts of ELN were measured in AUR cartilage (>15% ELN content per sample wet mass). No effect of gender was observed for either auricular or nasoseptal samples. For auricular samples, significant differences between age groups for h, sGAG and HYP, and significant regional variations for Ein, σmax, Eeq, t1/2, h, DNA and sGAG were measured. However, only low correlations between mechanical and biochemical parameters were seen (R<0.44). In conclusion, this study established the first comprehensive mechanical and biochemical map of human auricular cartilage. Regional variations in mechanical and biochemical properties were demonstrated in the auricle. This finding highlights the importance of focusing future research on efforts to produce cartilage grafts with spatially tunable mechanics.

  5. Influence of biochemical composition on endplate cartilage tensile properties in the human lumbar spine.

    PubMed

    Fields, Aaron J; Rodriguez, David; Gary, Kaitlyn N; Liebenberg, Ellen C; Lotz, Jeffrey C

    2014-02-01

    Endplate cartilage integrity is critical to spine health and is presumably impaired by deterioration in biochemical composition. Yet, quantitative relationships between endplate biochemical composition and biomechanical properties are unavailable. Using endplate cartilage harvested from human lumbar spines (six donors, ages 51-67 years) we showed that endplate biochemical composition has a significant influence on its equilibrium tensile properties and that the presence of endplate damage associates with a diminished composition-function relationship. We found that the equilibrium tensile modulus (5.9 ± 5.7 MPa) correlated significantly with collagen content (559 ± 147 µg/mg dry weight, r(2)  = 0.35) and with the collagen/GAG ratio (6.0 ± 2.1, r(2)  = 0.58). Accounting for the damage status of the adjacent cartilage improved the latter correlation (r(2)  = 0.77) and indicated that samples with adjacent damage such as fissures and avulsions had a diminished modulus-collagen/GAG relationship (p = 0.02). Quasi-linear viscoelastic relaxation properties (C, t1 , and t2 ) did not correlate with biochemical composition. We conclude that reduced matrix quantity decreases the equilibrium tensile modulus of human endplate cartilage and that characteristics of biochemical composition that are independent of matrix quantity, that is, characteristics related to matrix quality, may also be important. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. A chemiluminescence biochemical oxygen demand measuring method.

    PubMed

    Nakamura, Hideaki; Abe, Yuta; Koizumi, Rui; Suzuki, Kyota; Mogi, Yotaro; Hirayama, Takumi; Karube, Isao

    2007-10-17

    A new chemiluminescence biochemical oxygen demand (BOD(CL)) determining method was studied by employing redox reaction between quinone and Baker's yeast. The measurement was carried out by utilizing luminol chemiluminescence (CL) reaction catalyzed by ferricyanide with oxidized quinone of menadione, and Saccharomyces cerevisiae using a batch-type luminometer. In this study, dimethyl sulfoxide was used as a solvent for menadione. After optimization of the measuring conditions, the CL response to hydrogen peroxide in the incubation mixture had a linear response between 0.1 and 100 microM H2O2 (r2=0.9999, 8 points, n=3, average of relative standard deviation; R.S.D.(av)=4.22%). Next, a practical relationship between the BOD(CL) response and the glucose glutamic acid concentration was obtained over a range of 11-220 mg O2 L(-1) (6 points, n=3, R.S.D.(av) 3.71%) with a detection limit of 5.5 mg O2 L(-1) when using a reaction mixture and incubating for only 5 min. Subsequently, the characterization of this method was studied. First, the BOD(CL) responses to 16 pure organic substances were examined. Second, the influences of chloride ions, artificial seawater, and heavy metal ions on the BOD(CL) response were investigated. Real sample measurements using river water were performed. Finally, BOD(CL) responses were obtained for at least 8 days when the S. cerevisiae suspension was stored at 4 degrees C (response reduction, 69.9%; R.S.D. for 5 testing days, 18.7%). BOD(CL) responses after 8 days and 24 days were decreased to 69.9% and 35.8%, respectively, from their original values (R.S.D. for 8 days involving 5 testing days, 18.7%).

  7. Pellagra and alcoholism: a biochemical perspective.

    PubMed

    Badawy, Abdulla A-B

    2014-01-01

    Historical and clinical aspects of pellagra and its relationship to alcoholism are reviewed from a biochemical perspective. Pellagra is caused by deficiency of niacin (nicotinic acid) and/or its tryptophan (Trp) precursor and is compounded by B vitamin deficiencies. Existence on maize or sorghum diets and loss of or failure to isolate niacin from them led to pellagra incidence in India, South Africa, Southern Europe in the 18th century and the USA following the civil war. Pellagra is also induced by drugs inhibiting the conversion of Trp to niacin and by conditions of gastrointestinal dysfunction. Skin photosensitivity in pellagra may be due to decreased synthesis of the Trp metabolite picolinic acid → zinc deficiency → decreased skin levels of the histidine metabolite urocanic acid and possibly also increased levels of the haem precursor 5-aminolaevulinic acid (5-ALA) and photo-reactive porphyrins. Depression in pellagra may be due to a serotonin deficiency caused by decreased Trp availability to the brain. Anxiety and other neurological disturbances may be caused by 5-ALA and the Trp metabolite kynurenic acid. Pellagra symptoms are resolved by niacin, but aggravated mainly by vitamin B6. Alcohol dependence can induce or aggravate pellagra by inducing malnutrition, gastrointestinal disturbances and B vitamin deficiencies, inhibiting the conversion of Trp to niacin and promoting the accumulation of 5-ALA and porphyrins. Alcoholic pellagra encephalopathy should be managed with niacin, other B vitamins and adequate protein nutrition. Future studies should explore the potential role of 5-ALA and also KA in the skin and neurological disturbances in pellagra.

  8. The ONIOM molecular dynamics method for biochemical applications: cytidine deaminase

    SciTech Connect

    Matsubara, Toshiaki; Dupuis, Michel; Aida, Misako

    2007-03-22

    Abstract We derived and implemented the ONIOM-molecular dynamics (MD) method for biochemical applications. The implementation allows the characterization of the functions of the real enzymes taking account of their thermal motion. In this method, the direct MD is performed by calculating the ONIOM energy and gradients of the system on the fly. We describe the first application of this ONOM-MD method to cytidine deaminase. The environmental effects on the substrate in the active site are examined. The ONIOM-MD simulations show that the product uridine is strongly perturbed by the thermal motion of the environment and dissociates easily from the active site. TM and MA were supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan. MD was supported by the Division of Chemical Sciences, Office of Basic Energy Sciences, and by the Office of Biological and Environmental Research of the U.S. Department of Energy DOE. Battelle operates Pacific Northwest National Laboratory for DOE.

  9. Automatising the analysis of stochastic biochemical time-series

    PubMed Central

    2015-01-01

    Background Mathematical and computational modelling of biochemical systems has seen a lot of effort devoted to the definition and implementation of high-performance mechanistic simulation frameworks. Within these frameworks it is possible to analyse complex models under a variety of configurations, eventually selecting the best setting of, e.g., parameters for a target system. Motivation This operational pipeline relies on the ability to interpret the predictions of a model, often represented as simulation time-series. Thus, an efficient data analysis pipeline is crucial to automatise time-series analyses, bearing in mind that errors in this phase might mislead the modeller's conclusions. Results For this reason we have developed an intuitive framework-independent Python tool to automate analyses common to a variety of modelling approaches. These include assessment of useful non-trivial statistics for simulation ensembles, e.g., estimation of master equations. Intuitive and domain-independent batch scripts will allow the researcher to automatically prepare reports, thus speeding up the usual model-definition, testing and refinement pipeline. PMID:26051821

  10. Biochemical Analyses of Dissimilatory Iron Reduction by Shewanella oneidensis

    NASA Astrophysics Data System (ADS)

    Ruebush, S. S.; Tien, M.; Icopini, G. A.; Brantley, S. L.

    2002-12-01

    Shewanella oneidensis demonstrates respiratory flexibility by the transfer of electrons to Fe (III) and Mn (IV) oxides under anaerobic conditions. Researchers postulate that the bacterium utilizes surface proteins to facilitate the respiratory mechanism for dissimilatory iron(III) reduction. Previous genetic and biochemical studies has shown that iron reduction is associated with the outer membrane of the cell. The identity of the terminal reductase is not yet known. S. oneidensis has been shown to use soluble extra-cellular compounds to facilitate iron(III) reduction as well as expression of novel proteins on the cell surface when interacting with iron(III) oxides. Our results show that the outer membrane fraction possess enzymatic activity for converting Fe(III) to Fe(II) as measured by ferrozine complexation. AQDS, extra-cellular organic extracts, and iron(III) both soluble and solid have been assayed for activity with outer membrane fractions. Zymograms of the membrane fractions separated by isoelectric focusing and native PAGE electrophoresis stained using ferrozine have implicated proteins that are directly involved in the Fe(III) reduction process. A proteomics analysis of outer membrane proteins has also been implemented to identify different expression patterns under Fe(III) reducing conditions. Proteins that are unique to Fe(III) reduction have been isolated and identified using N-terminal sequence analysis. We will also attempt to examine the effect of enzymatic iron(III) reduction on isotopic partitioning from in vitro assays.

  11. Fungi in freshwaters: ecology, physiology and biochemical potential.

    PubMed

    Krauss, Gerd-Joachim; Solé, Magali; Krauss, Gudrun; Schlosser, Dietmar; Wesenberg, Dirk; Bärlocher, Felix

    2011-07-01

    Research on freshwater fungi has concentrated on their role in plant litter decomposition in streams. Higher fungi dominate over bacteria in terms of biomass, production and enzymatic substrate degradation. Microscopy-based studies suggest the prevalence of aquatic hyphomycetes, characterized by tetraradiate or sigmoid spores. Molecular studies have consistently demonstrated the presence of other fungal groups, whose contributions to decomposition are largely unknown. Molecular methods will allow quantification of these and other microorganisms. The ability of aquatic hyphomycetes to withstand or mitigate anthropogenic stresses is becoming increasingly important. Metal avoidance and tolerance in freshwater fungi implicate a sophisticated network of mechanisms involving external and intracellular detoxification. Examining adaptive responses under metal stress will unravel the dynamics of biochemical processes and their ecological consequences. Freshwater fungi can metabolize organic xenobiotics. For many such compounds, terrestrial fungal activity is characterized by cometabolic biotransformations involving initial attack by intracellular and extracellular oxidative enzymes, further metabolization of the primary oxidation products via conjugate formation and a considerable versatility as to the range of metabolized pollutants. The same capabilities occur in freshwater fungi. This suggests a largely ignored role of these organisms in attenuating pollutant loads in freshwaters and their potential use in environmental biotechnology. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  12. Label-Free Optical Ring Resonator Bio/Chemical Sensors

    NASA Astrophysics Data System (ADS)

    Zhu, Hongying; Suter, Jonathan D.; Fan, Xudong

    Optical micro-ring resonator sensors are an emerging category of label-free optical sensors for bio/chemical sensing that have recently been under intensive investigation. Researchers of this technology have been motivated by a tremendous breadth of different applications, including medical diagnosis, environmental monitoring, homeland security, and food quality control, which require sensitive analytical tools. Ring resonator sensors use total internal reflection to support circulating optical resonances called whispering gallery modes (WGMs). The WGMs have an evanescent field of several hundred nanometers into the surrounding medium, and can therefore detect the refractive index change induced when the analyte binds to the resonator surface. Despite the small physical size of a resonator, the circulating nature of the WGM creates extremely long effective lengths, greatly increasing light-matter interaction and improving its sensing performance. Moreover, only small sample volume is needed for detection because the sensors can be fabricated in sizes well below 100 μm. The small footprint allows integration of those ring resonator sensors onto lab-on-a-chip types of devices for multiplexed detection.

  13. Mammalian cells exposed to ionizing radiation: Structural and biochemical aspects.

    PubMed

    Sabanero, Myrna; Azorín-Vega, Juan Carlos; Flores-Villavicencio, Lérida Liss; Castruita-Dominguez, J Pedro; Vallejo, Miguel Angel; Barbosa-Sabanero, Gloria; Cordova-Fraga, Teodoro; Sosa-Aquino, Modesto

    2016-02-01

    Acute or chronic exposure to ionizing radiation is a factor that may be hazardous to health. It has been reported that exposure to low doses of radiation (less than 50 mSv/year) and subsequently exposure to high doses produces greater effects in people. It has been reported that people who have been exposed to low doses of radiation (less than 50 mSv/year) and subsequently are exposed to high doses, have greater effects. However, at a molecular and biochemical level, it is an unknown alteration. This study, analyzes the susceptibility of a biological system (HeLa ATCC CCL-2 human cervix cancer cell line) to ionizing radiation (6 and 60 mSv/90 s). Our research considers multiple variables such as: total protein profile, mitochondrial metabolic activity (XTT assay), cell viability (Trypan blue exclusion assay), cytoskeleton (actin microfilaments), nuclei (DAPI), and genomic DNA. The results indicate, that cells exposed to ionizing radiation show structural alterations in nuclear phenotype and aneuploidy, further disruption in the tight junctions and consequently on the distribution of actin microfilaments. Similar alterations were observed in cells treated with a genotoxic agent (200 μM H2O2/1h). In conclusion, this multi-criteria assessment enables precise comparisons of the effects of radiation between various line cells. However, it is necessary to determine stress markers for integration of the effects of ionizing radiation.

  14. The yeast actin cytoskeleton: from cellular function to biochemical mechanism.

    PubMed

    Moseley, James B; Goode, Bruce L

    2006-09-01

    All cells undergo rapid remodeling of their actin networks to regulate such critical processes as endocytosis, cytokinesis, cell polarity, and cell morphogenesis. These events are driven by the coordinated activities of a set of 20 to 30 highly conserved actin-associated proteins, in addition to many cell-specific actin-associated proteins and numerous upstream signaling molecules. The combined activities of these factors control with exquisite precision the spatial and temporal assembly of actin structures and ensure dynamic turnover of actin structures such that cells can rapidly alter their cytoskeletons in response to internal and external cues. One of the most exciting principles to emerge from the last decade of research on actin is that the assembly of architecturally diverse actin structures is governed by highly conserved machinery and mechanisms. With this realization, it has become apparent that pioneering efforts in budding yeast have contributed substantially to defining the universal mechanisms regulating actin dynamics in eukaryotes. In this review, we first describe the filamentous actin structures found in Saccharomyces cerevisiae (patches, cables, and rings) and their physiological functions, and then we discuss in detail the specific roles of actin-associated proteins and their biochemical mechanisms of action.

  15. Genetic, Biochemical and Clinical Insights into Primary Congenital Glaucoma

    PubMed Central

    Faiq, Muneeb; Sharma, Reetika; Dada, Rima; Mohanty, Kuldeep; Saluja, Daman

    2013-01-01

    ABSTRACT Glaucoma is an irreversible form of optic neuropathy in which the optic nerve suffers damage in a characteristic manner with optic nerve cupping and retinal ganglion cell death. Primary congenital glaucoma (PCG) is an idiopathic irreversible childhood blinding disorder which manifests at birth or within the first year of life. PCG presents with a classical triad of symptoms (viz epiphora, photophobia and blepharospasm) though there are many additional symptoms, including large eye ball and hazy cornea. The only anatomical anomaly found in PCG is trabecular meshwork (TM) dysgenesis. PCG is an inheritable disease with established genetic etiology. It transmits through autosomal recessive mode. A number of cases are sporadic also. Mutations in many genes have been found to be causative in PCG and many are yet to be found. Mutations in cytochrome P4501B1 (CYP1B1) gene have been found to be the predominant cause of PCG. Other genes that have been implicated in PCG etiology are myocilin, Forkhead-related transcription factor C1 (FOXC1) and latent transforming growth factor beta-binding protein 2 (LTBP2). Mutations in these genes have been reported from many parts of the world. In addition to this, mitochondrial genome mutations are also thought to be involved in its pathogenesis. There appears to be some mechanism involving more than one genetic factor. In this review, we will discuss the various clinical, biochemical and genetic aspects of PCG. We emphasize that etiology of PCG does not lie in a single gene or genetic factor. Research needs to be oriented into a direction where gene-gene interactions, ocular embryology, ophthalmic metabolism and systemic oxidative status need to be studied in order to understand this disorder. We also accentuate the need for ophthalmic genetic facilities in all ophthalmology setups. How to cite this article: Faiq M, Sharma R, Dada R, Mohanty K, Saluja D, Dada T. Genetic, Biochemical and Clinical Insights into Primary Congenital

  16. Genetic, Biochemical and Clinical Insights into Primary Congenital Glaucoma.

    PubMed

    Faiq, Muneeb; Sharma, Reetika; Dada, Rima; Mohanty, Kuldeep; Saluja, Daman; Dada, Tanuj

    2013-01-01

    Glaucoma is an irreversible form of optic neuropathy in which the optic nerve suffers damage in a characteristic manner with optic nerve cupping and retinal ganglion cell death. Primary congenital glaucoma (PCG) is an idiopathic irreversible childhood blinding disorder which manifests at birth or within the first year of life. PCG presents with a classical triad of symptoms (viz epiphora, photophobia and blepharospasm) though there are many additional symptoms, including large eye ball and hazy cornea. The only anatomical anomaly found in PCG is trabecular meshwork (TM) dysgenesis. PCG is an inheritable disease with established genetic etiology. It transmits through autosomal recessive mode. A number of cases are sporadic also. Mutations in many genes have been found to be causative in PCG and many are yet to be found. Mutations in cytochrome P4501B1 (CYP1B1) gene have been found to be the predominant cause of PCG. Other genes that have been implicated in PCG etiology are myocilin, Forkhead-related transcription factor C1 (FOXC1) and latent transforming growth factor beta-binding protein 2 (LTBP2). Mutations in these genes have been reported from many parts of the world. In addition to this, mitochondrial genome mutations are also thought to be involved in its pathogenesis. There appears to be some mechanism involving more than one genetic factor. In this review, we will discuss the various clinical, biochemical and genetic aspects of PCG. We emphasize that etiology of PCG does not lie in a single gene or genetic factor. Research needs to be oriented into a direction where gene-gene interactions, ocular embryology, ophthalmic metabolism and systemic oxidative status need to be studied in order to understand this disorder. We also accentuate the need for ophthalmic genetic facilities in all ophthalmology setups. How to cite this article: Faiq M, Sharma R, Dada R, Mohanty K, Saluja D, Dada T. Genetic, Biochemical and Clinical Insights into Primary Congenital Glaucoma

  17. Biochemical mediator demand--a novel rapid alternative for measuring biochemical oxygen demand.

    PubMed

    Pasco, N; Baronian, K; Jeffries, C; Hay, J

    2000-05-01

    The biochemical oxygen demand (BOD) test (BOD5) is a crucial environmental index for monitoring organic pollutants in waste water but is limited by the 5-day requirement for completing the test. We have optimised a rapid microbial technique for measuring the BOD of a standard BOD5 substrate (150 mg glucose/l, 150 mg glutamic acid/l) by quantifying an equivalent biochemical mediator demand in the absence of oxygen. Elevated concentrations of Escherichia coli were incubated with an excess of redox mediator, potassium hexacyanoferrate(III), and a known substrate for 1 h at 37 degrees C without oxygen. The addition of substrate increased the respiratory activity of the microorganisms and the accumulation of reduced mediator; the mediator was subsequently re-oxidised at a working electrode generating a current quantifiable by a coulometric transducer. Catabolic conversion efficiencies exceeding 75% were observed for the oxidation of the standard substrate. The inclusion of a mediator allowed a higher co-substrate concentration compared to oxygen and substantially reduced the incubation time from 5 days to 1 h. The technique replicates the traditional BOD5 method, except that a mediator is substituted for oxygen, and we aim to apply the principle to measure the BOD of real waste streams in future work.

  18. Are There Any Promising Biochemical Correlates of Achievement Behavior and Motivation? The Evidence for Serum Uric Acid and Serum Cholesterol

    ERIC Educational Resources Information Center

    Kasl, Stanislav V.

    1974-01-01

    This review examines the available evidence in support of the argument that serum uric acid (SUA) possesses considerable promise as an indicator of one type of biochemical influence on achievement behavior. The evidence arguing for further research into the role of serum cholesterol in achievement behavior is also examined. (Author/JR)

  19. Myoinositol Attenuates the Cell Loss and Biochemical Changes Induced by Kainic Acid Status Epilepticus

    PubMed Central

    Kikvidze, Marina

    2016-01-01

    Identification of compounds preventing or modifying the biochemical changes that underlie the epileptogenesis process and understanding the mechanism of their action are of great importance. We have previously shown that myoinositol (MI) daily treatment for 28 days prevents certain biochemical changes that are triggered by kainic acid (KA) induced status epilepticus (SE). However in these studies we have not detected any effects of MI on the first day after SE. In the present study we broadened our research and focused on other molecular and morphological changes at the early stages of SE induced by KA and effects of MI treatment on these changes. The increase in the amount of voltage-dependent anionic channel-1 (VDAC-1), cofilin, and caspase-3 activity was observed in the hippocampus of KA treated rats. Administration of MI 4 hours later after KA treatment abolishes these changes, whereas diazepam treatment by the same time schedule has no significant influence. The number of neuronal cells in CA1 and CA3 subfields of hippocampus is decreased after KA induced SE and MI posttreatment significantly attenuates this reduction. No significant changes are observed in the neocortex. Obtained results indicate that MI posttreatment after KA induced SE could successfully target the biochemical processes involved in apoptosis, reduces cell loss, and can be successfully used in the future for translational research. PMID:27642592

  20. SEROLOGICAL AND BIOCHEMICAL GENETIC MARKERS AND THEIR ASSOCIATIONS WITH PSYCHIATRIC DISORDERS : A REVIEW

    PubMed Central

    Balgir, R.S.

    1983-01-01

    SUMMARY The studies pertaining to associations of serological and biochemical genetic markers (blood groups in particular and scrum proteins and enzymes in general) with the psychiatric disorders such as psychoses in general, Schizophrenia, manic-depressive psychosis including unipolar and bipolar affective disorders and neuroses have been critically examined. The reasons for inconsistent findings of various investigators have been pointed out to assist the future researchers to overcome the previous drawbacks. Implications of associations of genetic markers with the psychiatric disorders have been discussed and future areas of research suggested. PMID:21847304

  1. Biochemical recurrence after definitive prostate cancer therapy. Part I: defining and localizing biochemical recurrence of prostate cancer.

    PubMed

    Ward, John F; Moul, Judd W

    2005-05-01

    The introduction of prostate-specific antigen into clinical practice heralded a dramatic shift in the epidemiology of prostate cancer. The diagnosis and treatment of lower stage disease in younger men with fewer competing co-morbidities has resulted in a longer period of post-treatment cancer surveillance and the potential for disease recurrence. Life-long periodic prostate-specific antigen testing for biochemical recurrence is standard of care; however, there is no single definition of biochemical recurrence that reliably predicts clinical recurrence. This review explores the complexities of biochemical recurrence, a thorough understanding of which is crucial to making appropriate treatment decisions after primary treatment. It also evaluates the array of diagnostic tests frequently employed when biochemical recurrence has occurred. There is a disconnection between biochemical recurrence and progression to clinical disease. The definition of biochemical recurrence varies both by the prostate-specific antigen cut-point used and by the primary therapy employed. Furthermore, biochemical recurrence by itself appears not to be as reliable a predictor of eventual clinical recurrence as prostate-specific antigen doubling time. Current imaging modalities are rarely useful in localizing disease when biochemical recurrence is first detected. The correct interpretation of biochemical recurrence is crucial to treatment decision-making. New data show that prostate-specific antigen doubling time during prostate-specific antigen recurrence may be a valid surrogate for death from the disease. The potential therefore exists for prostate-specific antigen doubling time to be accepted as a trial endpoint, which might accelerate drug approval by the United States Food and Drug Administration.

  2. Comparative study of the biochemical properties of proteasomes in domestic animals.

    PubMed

    Raule, Mary; Cerruti, Fulvia; Cascio, Paolo

    2015-07-15

    Information on the biochemical properties of proteasomes is lacking or, at best, only fragmentary for most species of veterinary interest. Moreover, direct comparison of the limited data available on the enzymatic features of proteasomes in domestic animals is rendered difficult due to the heterogeneity of the experimental settings used. This represents a clear drawback in veterinary research, given the crucial involvement of proteasomes in control of several physiological and pathological processes. We performed the first comparative analysis of key biochemical properties of proteasomes obtained from 8 different domestic mammals. Specifically, we investigated the three main peptidase activities of constitutive and immunoproteasomes in parallel and systematically checked the sensitivity of the chymotryptic site to three of the most potent and selective inhibitors available. Overall, there was substantial similarity in the enzymatic features of proteasomes among the species examined, although some interesting species-specific features were observed.

  3. Comparison of cold resistance physiological and biochemical features of four Herba Rhodiola seedlings under low temperature

    PubMed Central

    He, Shuling; Zhao, Kentian; Ma, Lingfa; Yang, Jingjun; Chang, Yuwei; Ashraf, Muhammad Aqeel

    2015-01-01

    To discuss the cold resistance performance of different Herba Rhodiolae and successfully transplant Herba Rhodiolae to the Gansu plateau area for nursing, domestication and planting, this paper systematically studies six physiological and biochemical features of Rhodiola kirilowii, Rhodiola algida, Rhodiola crenulata and Herba Rhodiolae that are closely associated with cold resistance features and concludes with the cold resistance capability of Rhodiola kirilowii. In the selected six main indexes of the Herba Rhodiolae, the POD, SOD and CAT activity and MDA and Pro content in the leaf are the main physiological and biochemical indexes to indicate the cold resistance performance of four Herba Rhodiolae seedlings and can be regarded as the preliminary indexes to assess the winter performance of Herba Rhodiolae. The research work will provide the theoretical basis for the wild variants of Herba Rhodiolae and GAPJ base construction. PMID:26981000

  4. Organic solvent pretreatment of lignocellulosic biomass for biofuels and biochemicals: A review.

    PubMed

    Zhang, Ke; Pei, Zhijian; Wang, Donghai

    2016-01-01

    Lignocellulosic biomass represents the largest potential volume and lowest cost for biofuel and biochemical production. Pretreatment is an essential component of biomass conversion process, affecting a majority of downstream processes, including enzymatic hydrolysis, fermentation, and final product separation. Organic solvent pretreatment is recognized as an emerging way ahead because of its inherent advantages, such as the ability to fractionate lignocellulosic biomass into cellulose, lignin, and hemicellulose components with high purity, as well as easy solvent recovery and solvent reuse. Objectives of this review were to update and extend previous works on pretreatment of lignocellulosic biomass for biofuels and biochemicals using organic solvents, especially on ethanol, methanol, ethylene glycol, glycerol, acetic acid, and formic acid. Perspectives and recommendations were given to fully describe implementation of proper organic solvent pretreatment for future research.

  5. Design and implementation of multi-campus, modular master classes in biochemical engineering

    NASA Astrophysics Data System (ADS)

    Wuyts, Niek; Bruneel, Dorine; Meyers, Myriam; Van Hoof, Etienne; De Vos, Leander; Langie, Greet; Rediers, Hans

    2015-07-01

    The Master of Science in engineering technology: biochemical engineering is organised in KU Leuven at four geographically dispersed campuses. To sustain the Master's programmes at all campuses, it is clear that a unique education profile at each campus is crucial. In addition, a rationalisation is required by increased cooperation, increased exchange of lecturers, and increased student mobility. To achieve this, a multicampus education system for the M.Sc. in engineering technology: biochemical engineering was developed by offering modules that are also available for students of other campuses. Such a module is primarily based on the research expertise present at the campus. In the development, special attention has been given to the optimal organisation of the modules, evaluation, required modifications of the current curricula, and the practical consequences for students following the module at another campus. Even in the first year of implementation, around 30% of the students followed a multicampus module, which indicates the potential success of the multicampus concept described here.

  6. Hematological and serum biochemical indices in healthy bonnet macaques (Macaca radiata)

    PubMed Central

    Pierre, Peter J.; Sequeira, Marlon K.; Corcoran, Christopher A.; Blevins, Maria W.; Gee, Melaney; Laudenslager, Mark L.; Bennett, Allyson J.

    2015-01-01

    Background Blood reference values for bonnet macaques (Macaca radiata) are limited. The goal of this study was to determine reference ranges for hematological and serum biochemical indices in healthy, socially housed bonnet macaques for males and females over a range of ages. Methods Blood hematological and serum biochemical values were obtained from 50 healthy bonnet macaques of both sexes and aged 10-234 months. Results Age and sex differences were present in a number of measures. Globulins, total protein, and creatinine (CREAT) values were highest among older subjects, while alkaline phophatase, albumin, and phosphorus values were higher in juveniles. Sex differences were present in concentrations of red blood cells and CREAT, with higher values in males. Conclusion The blood parameter data reported here as age-specific reference values for laboratory-housed, healthy bonnet macaques may be used to inform clinical care and laboratory primate research. PMID:21366603

  7. Reduction, integration and emergence in biochemical networks.

    PubMed

    Ricard, Jacques

    2004-12-01

    Most studies of molecular cell biology are based upon a process of decomposition of complex biological systems into their components, followed by the study of these components. The aim of the present paper is to discuss, on a physical basis, the internal logic of this process of reduction. The analysis is performed on simple biological systems, namely protein and metabolic networks. A multi-sited protein that binds two ligands x and y can be considered the simplest possible biochemical network. The organization of this network can be described through a comparison of three systems, i.e. XY, X and Y. X and Y are component sub-systems that collect states x(i) and y(j), respectively, i.e. protein states that have bound either i molecules of x (whether or not these states have also bound y), or j molecules of y (whether or not these states have bound x). XY is a system made up of the specific association of X and Y that collects states x(i)y(j). One can define mean self-informations per node of the network, , and . Reduction of the system XY into its components is possible if, and only if, ,is equal to the sum of and . If is smaller than the sum of and , the system is integrated, for it has less self-information than the set of its components X and Y. It can also occur that , be larger than the sum of and . Hence, the system XY displays negative integration and emergence of self-information relative to its components X and Y. Such a system is defined as complex. Positive or negative integration of the system implies it cannot be reduced to its components. The degree of integration can be measured by a function , called mutual information of integration. In the case of enzyme networks, emergence of self-information is associated with emergence of catalytic activity. Moreover, if the enzyme reaction is part of a metabolic sequence, its mutual information of integration can be

  8. Morphological and biochemical differentiation in Antarctic krill

    NASA Astrophysics Data System (ADS)

    Färber-Lorda, Jaime; Beier, Emilio; Mayzaud, Patrick

    2009-11-01

    During the February 1981 cruise FIBEX MD-25 between 30-50°E and 61-64°S, hydrography showed the presence of two gyres, confirmed by the geostrophic circulation relative to 1000 m from Levitus climatology, at the borders of these gyres concentrations of highly morphologically differentiated krill were found. Gaussian component analysis of krill samples, pooled by sectors, showed three cohorts of Euphausia superba in the western sector and one in the eastern sector. Across the sampling area, Thysanoessa macrura and E. superba occurred at separate stations. Analysis of cohorts in T. macrura separated two size groups in both the western and the eastern sectors. The use of a Differentiation Index (D.I.) [Färber-Lorda, J., 1990. Somatic length relationships and ontogenetic morphometric differentiation of Euphausia superba and Thysanoessa macrura of the southwest Indian Ocean during summer (February 1981). Deep-Sea Res. 37, 1135-1143.], based on somatic lengths, allows studying certain morphological differences within the populations sampled. Morphologically different and bigger males II (D.I. from 2.8 to 3.5) were present only in the southern transect while smaller males I (D.I. from 3.5 to 5.0) were present over the entire area. Biochemical composition of both species showed significant differences among stations for protein, lipids, and carbohydrates. A significant difference in lipid content was found between males I, and males II. For T. macrura, percentage of lipid content in mature animals was much higher than that in E. superba. The D.I. size distribution showed that when populations of E. superba were highly differentiated (corresponding to mature animals) in morphology, lipid content was high, and they were located near a gyre. Differences in morphometry can influence distribution of the species, because different developing stages have different swimming capacities. It is shown that, together with hydrography and trophic conditions, lipid content and

  9. Biochemical investigation of cypermethrin toxicity in rabbits.

    PubMed

    Dahamna, S; Harzallah, D; Guemache, A; Sekfali, N

    2009-01-01

    cypermethrin on the erythropoiesis. An increase of plasma enzyme activities in GOT, GPT and CPK were recorded, explain a high energy-generating product. An increase, in the plasma enzyme activity in Alkaline phosphatase, related to their role in the cell permeability. The histopathological results showed lesions and morphological changes of hepato-cellular, fibrosis and appearance of inflammatory infiltrate, confirmed disturbances of the biochemical parameters. These changes were much underlines during the animal toxicity.

  10. ALX receptor ligands define a biochemical endotype for severe asthma.

    PubMed

    Ricklefs, Isabell; Barkas, Ioanna; Duvall, Melody G; Cernadas, Manuela; Grossman, Nicole L; Israel, Elliot; Bleecker, Eugene R; Castro, Mario; Erzurum, Serpil C; Fahy, John V; Gaston, Benjamin M; Denlinger, Loren C; Mauger, David T; Wenzel, Sally E; Comhair, Suzy A; Coverstone, Andrea M; Fajt, Merritt L; Hastie, Annette T; Johansson, Mats W; Peters, Michael C; Phillips, Brenda R; Levy, Bruce D

    2017-07-20

    In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA). ALX expression and levels of proresolving ligands (lipoxin A4 [LXA4], 15-epi-LXA4, and annexin A1 [ANXA1]), and a proinflammatory ligand (serum amyloid A [SAA]) were measured in bronchoscopy samples collected in Severe Asthma Research Program-3 (SA [n = 69], non-SA [NSA, n = 51] or healthy donors [HDs, n = 47]). Bronchoalveolar lavage (BAL) fluid LXA4 and 15-epi-LXA4 were decreased and SAA was increased in SA relative to NSA. BAL macrophage ALX expression was increased in SA. Subjects with LXA4loSAAhi levels had increased BAL neutrophils, more asthma symptoms, lower lung function, increased relative risk for asthma exacerbation, sinusitis, and gastroesophageal reflux disease, and were assigned more frequently to SA clinical clusters. SAA and aliquots of LXA4loSAAhi BAL fluid induced IL-8 production by lung epithelial cells expressing ALX receptors, which was inhibited by coincubation with 15-epi-LXA4. Together, these findings have established an association between select ALX receptor ligands and asthma severity that define a potentially new biochemical endotype for asthma and support a pivotal functional role for ALX signaling in the fate of lung inflammation. Severe Asthma Research Program-3 (SARP-3; ClinicalTrials.gov NCT01606826)FUNDING Sources. National Heart, Lung and Blood Institute, the NIH, and the German Society of Pediatric Pneumology.

  11. ALX receptor ligands define a biochemical endotype for severe asthma

    PubMed Central

    Ricklefs, Isabell; Barkas, Ioanna; Duvall, Melody G.; Grossman, Nicole L.; Israel, Elliot; Bleecker, Eugene R.; Castro, Mario; Erzurum, Serpil C.; Fahy, John V.; Gaston, Benjamin M.; Denlinger, Loren C.; Mauger, David T.; Wenzel, Sally E.; Comhair, Suzy A.; Coverstone, Andrea M.; Fajt, Merritt L.; Hastie, Annette T.; Johansson, Mats W.; Peters, Michael C.; Phillips, Brenda R.; Levy, Bruce D.

    2017-01-01

    BACKGROUND. In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA). METHODS. ALX expression and levels of proresolving ligands (lipoxin A4 [LXA4], 15-epi-LXA4, and annexin A1 [ANXA1]), and a proinflammatory ligand (serum amyloid A [SAA]) were measured in bronchoscopy samples collected in Severe Asthma Research Program-3 (SA [n = 69], non-SA [NSA, n = 51] or healthy donors [HDs, n = 47]). RESULTS. Bronchoalveolar lavage (BAL) fluid LXA4 and 15-epi-LXA4 were decreased and SAA was increased in SA relative to NSA. BAL macrophage ALX expression was increased in SA. Subjects with LXA4loSAAhi levels had increased BAL neutrophils, more asthma symptoms, lower lung function, increased relative risk for asthma exacerbation, sinusitis, and gastroesophageal reflux disease, and were assigned more frequently to SA clinical clusters. SAA and aliquots of LXA4loSAAhi BAL fluid induced IL-8 production by lung epithelial cells expressing ALX receptors, which was inhibited by coincubation with 15-epi-LXA4. CONCLUSIONS. Together, these findings have established an association between select ALX receptor ligands and asthma severity that define a potentially new biochemical endotype for asthma and support a pivotal functional role for ALX signaling in the fate of lung inflammation. TRIAL REGISTRATION. Severe Asthma Research Program-3 (SARP-3; ClinicalTrials.gov NCT01606826) FUNDING Sources. National Heart, Lung and Blood Institute, the NIH, and the German Society of Pediatric Pneumology. PMID:28724795

  12. Biochemical observation during 28 days of space flight

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Kambaut, P. C.

    1975-01-01

    With the completion of the 28-day flight of Skylab 2, the sum of biochemical data on human reaction to the weightless environment was significantly extended both quantitatively and qualitatively. The biochemical studies were divided into two broad categories. One group included the more routine blood studies similar to those used in everyday medical practice. The second category encompassed those analyses used to investigate more thoroughly the endocrinological and fluid changes first seen in the crewmembers following the Gemini, Apollo, and Soviet missions. Significant biochemical changes were observed that varied in magnitude and direction, but all disappeared shortly after return to earth. Most of changes indicate successful adaptation by the body to the combined stresses of weightlessness. Results of the biochemical observation are presented in the form of data tables and graphs.

  13. A view of the history of biochemical engineering.

    PubMed

    Katzen, R; Tsao, G T

    2000-01-01

    The authors present a view of biochemical engineering by describing their personal interests and experience over the years involving mostly conversion of lignocellulosics into fuels and chemicals and the associated engineering subjects.

  14. Pleural, peritoneal and pericardial effusions – a biochemical approach

    PubMed Central

    Kopcinovic, Lara Milevoj; Culej, Jelena

    2014-01-01

    The pathological accumulation of serous fluids in the pleural, peritoneal and pericardial space occurs in a variety of conditions. Since patient management depends on right and timely diagnosis, biochemical analysis of extravascular body fluids is considered a valuable tool in the patient management process. The biochemical evaluation of serous fluids includes the determination of gross appearance, differentiation of transudative from exudative effusions and additional specific biochemical testing to assess the effusion etiology. This article summarized data from the most relevant literature concerning practice with special emphasis on usefulness of biochemical tests used for the investigation of pleural, peritoneal and pericardial effusions. Additionally, preanalytical issues concerning serous fluid analysis were addressed and recommendations concerning acceptable analytical practice in serous fluid analysis were presented. PMID:24627721

  15. CELLULAR, BIOCHEMICAL, AND MOLECULAR TECHNIQUES IN DEVELOPMENTAL TOXICOLOGY

    EPA Science Inventory

    Cellular, molecular and biochemical approaches vastly expand the possibilities for revealing the underlying mechanisms of developmental toxicity. The increasing interest in embryonic development as a model system for the study of gene expression has resulted in a cornucopia of i...

  16. Aquatic ecological biochemical investigations in the Lake Baikal region

    SciTech Connect

    Timofeeva, S.S.; Kozhova, O.M.

    1986-07-01

    The authors maintain that at the current level of investigations a constructive solution of the problem of protecting aquatic ecosystems is possible only on the basis of a thorough study of biochemical mechanisms of the interaction of biota and pollutants. They believe that in the program of investigations in the Baikal region, with consideration of the easy vulnerability of the aquatic ecosystems, ecological biochemical investigations should occupy one of the leading places. The authors suggest a method for the screening of xenobiotics, consisting of xenobiotics; chemical investigations; biochemical investigations of the properties of xenobiotics, and toxicological investigations of xenobiotics. The differences in the elimination of xenobiotics are considerable due to the species and biochemical characteristics of hydrophytes and chemical structure of the investigated toxicants. The results obtained in experiments with cyanide compounds are of considerable interest, since cyanides, the strongest poisons of animals, prove to be little toxic for higher aquatic plants and algae.

  17. A temperature-compensation mechanism in biochemical oscillation models

    NASA Astrophysics Data System (ADS)

    Bayramov, Sh. K.

    2017-07-01

    Different mechanisms that underlie temperature compensation of the frequency (period) of biochemical self-oscillations are considered. A systemic approach to the elucidation of the molecular nature of temperature compensation of the frequency of biochemical self-oscillations has been characterized as better substantiated. The phenomenon of temperature compensation is not unique for circadian oscillations ("biochemical clocks") but is rather an inherent property of all multidimensional chemical oscillators. Stages with negative coefficients of control over frequency were shown to be the components of the structure of "presetting generators" of biochemical self-oscillations, and the balancing role of these stages can be considered more important as believed earlier. The calculation of control coefficients showed that the elementary stages make unequal contributions to the mechanism that underlies temperature compensation; therefore, different mutations have dissimilar effects on the temperature compensation of the period of circadian oscillations in the respective mutants.

  18. 2011 Biomass Program Platform Peer Review: Biochemical Conversion

    SciTech Connect

    Pezzullo, Leslie

    2012-02-01

    This document summarizes the recommendations and evaluations provided by an independent external panel of experts at the 2011 U.S. Department of Energy Biomass Program’s Biochemical Conversion Platform Review meeting.

  19. Systematic review of biochemical biomarkers for neck and upper-extremity musculoskeletal disorders.

    PubMed

    Gold, Judith E; Hallman, David M; Hellström, Fredrik; Björklund, Martin; Crenshaw, Albert G; Djupsjobacka, Mats; Heiden, Marina; Mathiassen, Svend Erik; Piligian, George; Barbe, Mary F

    2016-03-01

    This study systematically summarizes biochemical biomarker research in non-traumatic musculoskeletal disorders (MSD). Two research questions guided the review: (i) Are there biochemical markers associated with neck and upper-extremity MSD? and (ii) Are there biochemical markers associated with the severity of neck and upper-extremity MSD? A literature search was conducted in PubMed and SCOPUS, and 87 studies met primary inclusion criteria. Following a quality screen, data were extracted from 44 articles of sufficient quality. Most of the 87 studies were cross-sectional and utilized convenience samples of patients as both cases and controls. A response rate was explicitly stated in only 11 (13%) studies. Less than half of the studies controlled for potential confounding through restriction or in the analysis. Most sufficient-quality studies were conducted in older populations (mean age in one or more analysis group >50 years). In sufficient-quality articles, 82% demonstrated at least one statistically significant association between the MSD and biomarker(s) studied. Evidence suggested that: (i) the collagen-repair marker TIMP-1 is decreased in fibro proliferative disorders, (ii) 5-HT (serotonin) is increased in trapezius myalgia, and (iii) triglycerides are increased in a variety of MSD. Only 5 studies showed an association between a biochemical marker and MSD severity. While some MSD biomarkers were identified, limitations in the articles examined included possible selection bias, confounding, spectrum effect (potentially heterogeneous biomarker associations in populations according to symptom severity or duration), and insufficient attention to comorbid conditions. A list of recommendations for future studies is provided.

  20. Laetrile: A Study of Its Physicochemical and Biochemical Properties

    PubMed Central

    Levi, Leo; French, W. N.; Bickis, I. J.; Henderson, I. W. D.

    1965-01-01

    A study was made of the composition and biochemical behaviour of the drug, Laetrile, distributed for clinical trial in the United States and Canada. It was established that the Canadian and the American product are different pharmaceutical formulations, displaying different physicochemical and biochemical properties. The investigation demonstrated, furthermore, that neither preparation can be considered as a palliative in cancer therapy on the basis of the biological rationale advanced by their manufacturers. ImagesFig. 3 PMID:14281087

  1. Energy-based analysis of biochemical cycles using bond graphs.

    PubMed

    Gawthrop, Peter J; Crampin, Edmund J

    2014-11-08

    Thermodynamic aspects of chemical reactions have a long history in the physical chemistry literature. In particular, biochemical cycles require a source of energy to function. However, although fundamental, the role of chemical potential and Gibb's free energy in the analysis of biochemical systems is often overlooked leading to models which are physically impossible. The bond graph approach was developed for modelling engineering systems, where energy generation, storage and transmission are fundamental. The method focuses on how power flows between components and how energy is stored, transmitted or dissipated within components. Based on the early ideas of network thermodynamics, we have applied this approach to biochemical systems to generate models which automatically obey the laws of thermodynamics. We illustrate the method with examples of biochemical cycles. We have found that thermodynamically compliant models of simple biochemical cycles can easily be developed using this approach. In particular, both stoichiometric information and simulation models can be developed directly from the bond graph. Furthermore, model reduction and approximation while retaining structural and thermodynamic properties is facilitated. Because the bond graph approach is also modular and scaleable, we believe that it provides a secure foundation for building thermodynamically compliant models of large biochemical networks.

  2. Energy-based analysis of biochemical cycles using bond graphs

    PubMed Central

    Gawthrop, Peter J.; Crampin, Edmund J.

    2014-01-01

    Thermodynamic aspects of chemical reactions have a long history in the physical chemistry literature. In particular, biochemical cycles require a source of energy to function. However, although fundamental, the role of chemical potential and Gibb's free energy in the analysis of biochemical systems is often overlooked leading to models which are physically impossible. The bond graph approach was developed for modelling engineering systems, where energy generation, storage and transmission are fundamental. The method focuses on how power flows between components and how energy is stored, transmitted or dissipated within components. Based on the early ideas of network thermodynamics, we have applied this approach to biochemical systems to generate models which automatically obey the laws of thermodynamics. We illustrate the method with examples of biochemical cycles. We have found that thermodynamically compliant models of simple biochemical cycles can easily be developed using this approach. In particular, both stoichiometric information and simulation models can be developed directly from the bond graph. Furthermore, model reduction and approximation while retaining structural and thermodynamic properties is facilitated. Because the bond graph approach is also modular and scaleable, we believe that it provides a secure foundation for building thermodynamically compliant models of large biochemical networks. PMID:25383030

  3. [Fifty years of cooperation--FEBS and Polish Biochemical Society].

    PubMed

    Barańska, Jolanta

    2014-01-01

    This year, the Federation of European Biochemical Societies (FEBS) celebrates its 50th anniversary. The Polish Biochemical Society, represented by the Society's President, Kazimierz Zakrzewski, was a founding member of the organization. The text presents a history of collaboration between FEBS and Polish Biochemical Society, the participation of Polish Biochemical Society members in different FEBS activities, as well as the role they played in running the Federation. Author describes FEBS Congresses which taken place in Warsaw, the first 3rd FEBS Meeting in 1966 and then 29th Congress in 2004. The profiles of Jakub Karol Parnas, the founding father of the Polish biochemistry and some crucial Presidents of the Society, are also presented. The text describes Parnas Conferences, organized jointly by Polish and Ukrainian Biochemical Societies from 1996, and growing from 2011 into three-nation event with participation of Ukrainian, Israeli and Polish scientists, largely due to significant help from FEBS. Summarizing the last few years, author judge the cooperation between the Federation and the Polish Biochemical Society as optimal.

  4. Phaeochromocytoma: diagnostic challenges for biochemical screening and diagnosis.

    PubMed

    Barron, Jeffrey

    2010-08-01

    The aim of this article is to provide knowledge of the origin of catecholamines and metabolites so that there can be an informed approach to the methods for biochemical screening for a possible phaeochromocytoma; The article includes a review of catecholamine and metadrenaline metabolism, with methods used in biochemical screening. In the adrenal medulla and a phaeochromocytoma, catecholamines continuously leak from chromaffin granules into the cytoplasm and are converted to metadrenalines. For a phaeochromocytoma to become biochemically detectable, metnoradrenaline secretion needs to rise fourfold, whereas noradrenaline secretion needs to rise 15-fold. The prevalence of a sporadic phaeochromocytoma is low; therefore false-positive results exceed true-positive results. Assay sensitivity is high because it is important not to miss a possible phaeochromocytoma. The use of urine or plasma fractionated metadrenalines as the first-line test has been recommended due to improved sensitivity. A negative result excludes a phaeochromocytoma. Only after a sporadic phaeochromocytoma has been diagnosed biochemically is it cost effective to request imaging. Sensitivities and specificities of the assays differ according to pre-test probabilities of the presence of a phaeochromocytoma, with hereditary and incidentalomas having a higher pre-test probability than sporadic phaeochromocytoma. In conclusion, in screening for a possible phaeochromocytoma, biochemical investigations should be completed first to exclude or establish the diagnosis. The preferred biochemical screening test is fractionated metadrenalines, including methoxytyramine so as not to miss dopamine-secreting tumours.

  5. Between biochemists and embryologists -- the biochemical study of embryonic induction in the 1930s.

    PubMed

    Armon, Rony

    2012-01-01

    The discovery by Hans Spemann of the "organizer" tissue and its ability to induce the formation of the amphibian embryo's neural tube inspired leading embryologists to attempt to elucidate embryonic inductions' underlying mechanism. Joseph Needham, who during the 1930s conducted research in biochemical embryology, proposed that embryonic induction is mediated by a specific chemical entity embedded in the inducing tissue, surmising that chemical to be a hormone of sterol-like structure. Along with embryologist Conrad H. Waddington, they conducted research aimed at the isolation and functional characterization of the underlying agent. As historians clearly pointed out, embryologists came to question Needham's biochemical approach; he failed to locate the hormone he sought and eventually abandoned his quest. Yet, this study finds that the difficulties he ran into resulted primarily from the limited conditions for conducting his experiments at his institute. In addition, Needham's research reflected the interests of leading biochemists in hormone and cancer research, because it offered novel theoretical models and experimental methods for engaging with the function of the hormones and carcinogens they isolated. Needham and Waddington were deterred neither by the mounting challenges nor by the limited experimental infrastructure. Like their colleagues in hormone and cancer research, they anticipated difficulties in attempting to establish causal links between complex biological phenomena and simple chemical triggering.

  6. Identification of another actin-related protein (Arp) 2/3 complex binding site in neural Wiskott-Aldrich syndrome protein (N-WASP) that complements actin polymerization induced by the Arp2/3 complex activating (VCA) domain of N-WASP.

    PubMed

    Suetsugu, S; Miki, H; Takenawa, T

    2001-08-31

    Neural Wiskott-Aldrich syndrome protein (N-WASP) is an essential regulator of actin cytoskeleton formation via its association with the actin-related protein (Arp) 2/3 complex. It is believed that the C-terminal Arp2/3 complex-activating domain (verprolin homology, cofilin homology, and acidic (VCA) or C-terminal region of WASP family proteins domain) of N-WASP is usually kept masked (autoinhibition) but is opened upon cooperative binding of upstream regulators such as Cdc42 and phosphatidylinositol 4,5-bisphosphate (PIP2). However, the mechanisms of autoinhibition and association with Arp2/3 complex are still unclear. We focused on the acidic region of N-WASP because it is thought to interact with Arp2/3 complex and may be involved in autoinhibition. Partial deletion of acidic residues from the VCA portion alone greatly reduced actin polymerization activity, demonstrating that the acidic region contributes to Arp2/3 complex-mediated actin polymerization. Surprisingly, the same partial deletion of the acidic region in full-length N-WASP led to constitutive activity comparable with the activity seen with the VCA portion. Therefore, the acidic region in full-length N-WASP plays an indispensable role in the formation of the autoinhibited structure. This mutant contains WASP-homology (WH) 1 domain with weak affinity to the Arp2/3 complex, leading to activity in the absence of part of the acidic region. Furthermore, the actin comet formed by the DeltaWH1 mutant of N-WASP was much smaller than that of wild-type N-WASP. Partial deletion of acidic residues did not affect actin comet size, indicating the importance of the WH1 domain in actin structure formation. Collectively, the acidic region of N-WASP plays an essential role in Arp2/3 complex activation as well as in the formation of the autoinhibited structure, whereas the WH1 domain complements the activation of the Arp2/3 complex achieved through the VCA portion.

  7. Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination.

    PubMed

    Woodman, Andrew; Arnold, Jamie J; Cameron, Craig E; Evans, David J

    2016-08-19

    Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3' non-coding region we have further developed a cell-based assay (the 3'CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. A proposed biochemical mechanism involving hemoglobin for blast overpressure-induced injury.

    PubMed

    Elsayed, N M; Gorbunov, N V; Kagan, V E

    1997-07-25

    Blast overpressure (BOP) is the abrupt, rapid, rise in atmospheric pressure resulting from explosive detonation, firing of large-caliber weapons, and accidental occupational explosions. Exposure to incident BOP waves causes internal injuries, mostly to the hollow organs, particularly the ears, lungs and gastrointestinal tract. BOP-induced injury used to be considered of military concern because it occurred mostly in military environments during military actions or training, and to a lesser extent during civilian occupational accidents. However, in recent years with the proliferation of indiscriminate terrorist bombings worldwide involving civilians, blast injury has become a societal concern, and the need to understand the biochemical and molecular mechanism(s) of injury, and to find new and effective methods for treatment gained importance. In general, past BOP research has focused on the physiological and pathological manifestations of incapacitation, thresholds of safety, and on predictive modeling. However, we have been studying the molecular mechanism of BOP-induced injury, and recently began to have an insight into that mechanism, and recognize the role of hemoglobin released during hemorrhage in catalyzing free radical reactions leading to oxidative stress. In this report we discuss the biochemical changes observed after BOP exposure in rat blood and lung tissue, and propose a biochemical mechanism for free radical-induced oxidative stress that can potentially complicate the injury. Moreover, we observed that some antioxidants can interact with Hb oxidation products (oxy-, met- and oxoferrylHb) and act as prooxidants that can increase the damage rather than decrease it.

  9. [Design of high-efficiency double compound parabolic concentrator system in near infrared noninvasive biochemical analysis].

    PubMed

    Gao, Jing; Lu, Qi-Peng; Peng, Zhong-Qi; Ding, Hai-Quan; Gao, Hong-Zhi

    2013-05-01

    High signal-to-noise ratio (SNR) of system is necessary to obtain accurate blood components in near infrared noninvasive biochemical analysis. In order to improve SNR of analytical system, high-efficiency double compound parabolic concentrator (DCPC) system was researched, which was aimed at increasing light utilization efficiency. Firstly, with the request of collection efficiency in near infrared noninvasive biochemical analysis, the characteristic of emergent rays through compound parabolic concentrator (CPC) was analyzed. Then the maximum focusing angle range of the first stage CPC was determined. Secondly, the light utilization efficiency of truncated type was compared with standard DCPC, thus the best structure parameters of DCPC system were optimized. Lastly, combined with optical parameters of skin tissue, calculations were operated when incident wavelength is 1 000 nm. The light utilization efficiency of DCPC system, CPC-focusing mirror system, and non-optical collecting system was calculated. The results show that the light utilization efficiency of the three optical systems is 1.46%, 0.84% and 0.26% respectively. So DCPC system enhances collecting ability for human diffuse reflection light, and helps improve SNR of noninvasive biochemical analysis system and overall analysis accuracy effectively.

  10. Estimating Biochemical Parameters of Tea (camellia Sinensis (L.)) Using Hyperspectral Techniques

    NASA Astrophysics Data System (ADS)

    Bian, M.; Skidmore, A. K.; Schlerf, M.; Liu, Y.; Wang, T.

    2012-07-01

    Tea (Camellia Sinensis (L.)) is an important economic crop and the market price of tea depends largely on its quality. This research aims to explore the potential of hyperspectral remote sensing on predicting the concentration of biochemical components, namely total tea polyphenols, as indicators of tea quality at canopy scale. Experiments were carried out for tea plants growing in the field and greenhouse. Partial least squares regression (PLSR), which has proven to be the one of the most successful empirical approach, was performed to establish the relationship between reflectance and biochemical concentration across six tea varieties in the field. Moreover, a novel integrated approach involving successive projections algorithms as band selection method and neural networks was developed and applied to detect the concentration of total tea polyphenols for one tea variety, in order to explore and model complex nonlinearity relationships between independent (wavebands) and dependent (biochemicals) variables. The good prediction accuracies (r2 > 0.8 and relative RMSEP < 10 %) achieved for tea plants using both linear (partial lease squares regress) and nonlinear (artificial neural networks) modelling approaches in this study demonstrates the feasibility of using airborne and spaceborne sensors to cover wide areas of tea plantation for in situ monitoring of tea quality cheaply and rapidly.

  11. The equation for prediction of blood viscosity from biochemical laboratory data

    NASA Astrophysics Data System (ADS)

    Sahin, B.; Yigitarslan, S.

    2015-03-01

    In most cases, the viscosity of blood is measured after adulteration with heparin or EDTA. The aim of the present research was to derive an equation that can be used for determination of viscosity from biochemical data. Blood samples taken from seven healthy people were analyzed in biochemical laboratory and their viscosities were measured by adding EDTA as anticoagulant. Ten parameters of biochemical laboratory including blood cells (erythrocytes, leukocytes, thrombocytes) and their functional products that directly affect the blood viscosity were chosen. Several equations relating viscosity to those parameters were derived by using a computer program. According to the regression analysis of the functions derived, the viscosity equation was obtained. This equation can be used for determination of blood viscosity from classical laboratory analysis. The advantages of using the derived equation are elimination of anticoagulant addition and elimination of Fahraeus_Lindquist effect. After proving that the equation is acceptable for numerous people, apparent viscosity changes can be followed during any disease and successfulness of anticoagulant drugs can be investigated.

  12. Biochemical and Immunological Markers of Over-Training

    PubMed Central

    Gleeson, Michael

    2002-01-01

    Athletes fail to perform to the best of their ability if they become infected, stale, sore or malnourished. Excessive training with insufficient recovery can lead to a debilitating syndrome in which performance and well being can be affected for months. Eliminating or minimizing these problems by providing advice and guidelines on training loads, recovery times, nutrition or pharmacological intervention and regular monitoring of athletes using an appropriate battery of markers can help prevent the development of an overtraining syndrome in athletes. The potential usefulness of objective physiological, biochemical and immunological markers of overtraining has received much attention in recent years. Practical markers would be ones that could be measured routinely in the laboratory and offered to athletes as part of their sports science and medical support. The identification of common factors among overtrained athletes in comparison with well-trained athletes not suffering from underperformance could permit appropriate intervention to prevent athletes from progressing to a more serious stage of the overtraining syndrome. To date, no single reliable objective marker of impending overtraining has been identified. Some lines of research do, however, show promise and are based on findings that overtrained athletes appear to exhibit an altered hormonal response to stress. For example, in response to a standardized bout (or repeated bouts) of high intensity exercise, overtrained athletes show a lower heart rate, blood lactate and plasma cortisol response. Several immune measures that can be obtained from a resting blood sample (e.g. the expression of specific cell surface proteins such as CD45RO+ on T-lymphocytes) also seem to offer some hope of identifying impending overtraining. If an athlete is suspected of suffering from overtraining syndrome, other measures will also required, if only to exclude other possible causes of underperformance including post-viral fatigue

  13. Biochemical and immunological markers of over-training.

    PubMed

    Gleeson, Michael

    2002-06-01

    Athletes fail to perform to the best of their ability if they become infected, stale, sore or malnourished. Excessive training with insufficient recovery can lead to a debilitating syndrome in which performance and well being can be affected for months. Eliminating or minimizing these problems by providing advice and guidelines on training loads, recovery times, nutrition or pharmacological intervention and regular monitoring of athletes using an appropriate battery of markers can help prevent the development of an overtraining syndrome in athletes. The potential usefulness of objective physiological, biochemical and immunological markers of overtraining has received much attention in recent years. Practical markers would be ones that could be measured routinely in the laboratory and offered to athletes as part of their sports science and medical support. The identification of common factors among overtrained athletes in comparison with well-trained athletes not suffering from underperformance could permit appropriate intervention to prevent athletes from progressing to a more serious stage of the overtraining syndrome. To date, no single reliable objective marker of impending overtraining has been identified. Some lines of research do, however, show promise and are based on findings that overtrained athletes appear to exhibit an altered hormonal response to stress. For example, in response to a standardized bout (or repeated bouts) of high intensity exercise, overtrained athletes show a lower heart rate, blood lactate and plasma cortisol response. Several immune measures that can be obtained from a resting blood sample (e.g. the expression of specific cell surface proteins such as CD45RO+ on T-lymphocytes) also seem to offer some hope of identifying impending overtraining. If an athlete is suspected of suffering from overtraining syndrome, other measures will also required, if only to exclude other possible causes of underperformance including post-viral fatigue

  14. Diabetes mellitus: biochemical, histological and microbiological aspects in periodontal disease.

    PubMed

    Marigo, L; Cerreto, R; Giuliani, M; Somma, F; Lajolo, C; Cordaro, M

    2011-07-01

    Relationship between diabetes mellitus (DM) and periodontal disease has been the subject of many studies that underline that diabetic patients are two/three times more susceptible to have an increased risk of periodontal disease, especially when metabolic control is inadequate. In this review the authors analyze, in diabetic patient, biochemical, histological and microbiological aspects of periodontal disease. Recent studies reported the results obtained in not diabetic patients, both periodontopatic and not: in periodontopatic subjects, the value of glycated hemoglobin was higher. As regards type 2 DM has a positive relationship between periodontal inflammation and glycemia, with good probabilities of disease development. Some Authors showed how the hygiene and the professional/domiciliary control could support a reduction of the glycate hemoglobin and, therefore, of the periodontal disease. The glucose accumulation in the crevicular fluid, noticed in pockets with a depth >4 mm, causes an increase of spirochetes and bacteria. Some research reported that scarcely controlled patients show high levels of interleukin-1beta (IL-1beta). This alteration together with the prolonged expression of tumor necrosis factor (TNF) could represent a mechanism used by bacteria to cause a major damage during the inflammation process, sometimes favoured by immunological defects, due to the mobilization of lymphocytes subpopulations. By measuring the values of TNF-a, fibrinogen, high sensitive capsule reactive protein (hs-CRP), IL-4, IL-6, IL-8, IL-10, at the beginning of non-surgical periodontal therapy and it has been after 3 months of treatment, noticed a relevant reduction only of TNF-a and fibrinogen. Concerning vascular alteration, vascular endothelium growing factor (VEGF) could play a major role in the tissues ischemia. The VEGF should determine the tissue ischemia, the angiogenesis and the alteration of glucose haematic level, in patients affected by microvasculopathies due

  15. Evaluation of Nutritional Biochemical Parameters in Haemodialysis Patients over a Ten-year Period.

    PubMed

    Alfonso, A I-Q; Castillo, R F; Gomez Jimenez, F J; Nuñez Negrillo, A M

    2015-06-01

    Protein-energy malnutrition as well as systemic inflammation and metabolic disorders are common in patients with chronic kidney failure, who require renal replacement therapy (haemodialysis). Such malnutrition is a factor that significantly contributes to their morbidity and mortality. This study evaluated the nutritional status of haemodialysis patients by assessing biochemical and anthropometric parameters in order to determine whether these patients suffered disorders reflecting nutritional deterioration directly related to time on haemodialysis. This research comprised 90 patients of both genders with chronic kidney failure, who regularly received haemodialysis at our unit over a period of ten years. The patients' blood was tested quarterly for plasma albumin, total cholesterol and total proteins, and tested monthly for transferrin. The patients' weight, height and body mass index (BMI) were monitored. Body mass index was calculated using the formula: weight (kg)/height (m2 ) and classified in one of the following categories defined in the World Health Organization (WHO) Global Database on Body Mass Index: (i) underweight [BMI < 18.50], (ii) normal [BMI 18.50 - 24.99], (iii) overweight [BMI 25 - 29.99], (iv) obese [BMI > 30]. In the ten-year period of the study, the patients experienced a substantial decline in their biochemical parameters. Nevertheless, their BMI did not show any significant changes despite the patients' state of malnutrition. The prevalence of malnutrition in haemodialysis patients was evident. Nevertheless, the BMI of the subjects did not correspond to the biochemical parameters measured. Consequently, the results showed that the nutritional deterioration of these patients was mainly reflected in their biochemical parameters rather than in their anthropometric measurements.

  16. Evaluation of Nutritional Biochemical Parameters in Haemodialysis Patients over a Ten-year Period

    PubMed Central

    Alfonso, AIQ; Castillo, RF; Jimenez, FJ Gomez; Negrillo, AM Nuñez

    2015-01-01

    ABSTRACT Aim: Protein-energy malnutrition as well as systemic inflammation and metabolic disorders are common in patients with chronic kidney failure who require renal replacement therapy (haemodialysis). Such malnutrition is a factor that significantly contributes to their morbidity and mortality. This study evaluated the nutritional status of haemodialysis patients by assessing biochemical and anthropometric parameters in order to determine whether these patients suffered disorders reflecting nutritional deterioration directly related to time on haemodialysis. Subjects and Method: This research comprised 90 patients of both genders with chronic kidney failure, who regularly received haemodialysis at our unit over a period of ten years. The patients' blood was tested quarterly for plasma albumin, total cholesterol and total proteins, and tested monthly for transferrin. The patients' weight, height and body mass index (BMI) were monitored. Body mass index was calculated using the formula: weight (kg)/height (m2) and classified in one of the following categories defined in the World Health Organization (WHO) Global Database on Body Mass Index: (i) underweight [BMI < 18.50], (ii) normal [BMI 18.50 – 24.99], (iii) overweight [BMI 25 – 29.99], (iv) obese [BMI ≥ 30]. Results: In the ten-year period of the study, the patients experienced a substantial decline in their biochemical parameters. Nevertheless, their BMI did not show any significant changes despite the patients' state of malnutrition. Conclusions: The prevalence of malnutrition in haemodialysis patients was evident. Nevertheless, the BMI of the subjects did not correspond to the biochemical parameters measured. Consequently, the results showed that the nutritional deterioration of these patients was mainly reflected in their biochemical parameters rather than in their anthropometric measurements. PMID:26426172

  17. SIM-GC-MS analysis of biochemical evolution in Amanita genus

    NASA Astrophysics Data System (ADS)

    Ristoiu, Dumitru; Kovacs, Emoke Dalma; Cobzac, Codruta; Parvu, Marcel; Ristoiu, Tania; Kovacs, Melinda Haydee

    2010-11-01

    Amanita is one of the most well known basidiomycetes genus throughout the world because some of its species that are acknowledged due to their toxic and/or hallucinogenic properties. Considering these properties in the last decades become more important for scientist to dignify exactly the chemical content of these mushroom species. Latter researches shown that A. phalloides contain two main groups of toxins: the amatoxins and the phallotoxins. As regards A. rubescens there are not so much studies referring to its biochemical "fingerprint". Two species (A. rubescens and A. phalloides) of Amanita genus were studied in order to determine the biochemical hall-mark at nanoscale for these basidiomycete's species. Parts as caps, gills, flesh and stem of these mushrooms were analyzed on quadrupole mass spectrometer engaged with a gas chromatograph (GC-qMS) using selective ion monitoring mode (SIM). The biochemical profiles of these species had shown the presence of compounds like fatty acid methyl esters (FAMEs), alkaloids, and volatile compounds (including alcohol compounds, carbonyl compounds, terpenes). The levels of biochemical compounds from these species were compared between the two types of species and also between young, mature and old samples for the same species as well as between the parts of mushroom. After this comparison were between the two species it was observed that in case of A. phalloides the alkaloid content were higher usually with almost 50 %. As regards presence of volatile compounds they have almost similar level in both mushroom species. Considering the levels of fatty acid methyl esters, their levels were higher with 30 - 40 % in case of A. rubescens.

  18. Microfluidics meets metabolomics to reveal the impact of Campylobacter jejuni infection on biochemical pathways.

    PubMed

    Mortensen, Ninell P; Mercier, Kelly A; McRitchie, Susan; Cavallo, Tammy B; Pathmasiri, Wimal; Stewart, Delisha; Sumner, Susan J

    2016-06-01

    Microfluidic devices that are currently being used in pharmaceutical research also have a significant potential for utilization in investigating exposure to infectious agents. We have established a microfluidic device cultured with Caco-2 cells, and utilized metabolomics to investigate the biochemical responses to the bacterial pathogen Campylobacter jejuni. In the microfluidic devices, Caco-2 cells polarize at day 5, are uniform, have defined brush borders and tight junctions, and form a mucus layer. Metabolomics analysis of cell culture media collected from both Caco-2 cell culture systems demonstrated a more metabolic homogenous biochemical profile in the media collected from microfluidic devices, compared with media collected from transwells. GeneGo pathway mapping indicated that aminoacyl-tRNA biosynthesis was perturbed by fluid flow, suggesting that fluid dynamics and shear stress impacts the cells translational quality control. Both microfluidic device and transwell culturing systems were used to investigate the impact of Campylobacter jejuni infection on biochemical processes. Caco-2 cells cultured in either system were infected at day 5 with C. jejuni 81-176 for 48 h. Metabolomics analysis clearly differentiated C. jejuni 81-176 infected and non-infected medias collected from the microfluidic devices, and demonstrated that C. jejuni 81-176 infection in microfluidic devices impacts branched-chain amino acid metabolism, glycolysis, and gluconeogenesis. In contrast, no distinction was seen in the biochemical profiles of infected versus non-infected media collected from cells cultured in transwells. Microfluidic culturing conditions demonstrated a more metabolically homogenous cell population, and present the opportunity for studying host-pathogen interactions for extended periods of time.

  19. Advances in drug discovery and biochemical studies.

    PubMed

    Kita, Kiyoshi; Shiomi, Kazuro; Omura, Satoshi

    2007-05-01

    Japanese researchers continue to discover new means to combat parasites and make important contributions toward developing tools for global control of parasitic diseases. Streptomyces avermectinius, the source of ivermectin, was discovered in Japan in the early 1970s and renewed and vigorous screening of microbial metabolites in recent years has led to the discovery of new antiprotozoals and anthelminthics, including antimalarial drugs. Intensive studies of parasite energy metabolism, such as NADH-fumarate reductase systems and the synthetic pathways of nucleic acids and amino acids, also contribute to the identification of novel and unique drug targets.

  20. Chemical and Biochemical Studies of PGBX.

    DTIC Science & Technology

    1980-08-30

    DLN N0014-7-Ci 3 nEECASEEEilI EEEmEm ErI- 0OFFICE OF NAVAL RESEARCH Contract N00014-77-C-0340 r - Task No. NR 206-003 ANNUAL REPORT NO. 2 Chemical and...in the membrane. The ionophoretic properties of PGBx have been confirmed by Weissmann, et al (Weissmann, G., Anderson, P., Serhan , C., Samuelson, E...Nelson (St. Joseph’s University), Dr. R . Doskotch (Ohio State University), Dr. K. Biemann (MIT) and Dr. D. Trainor (Columbia University). This report does

  1. Biochemical modeling with Systems Biology Graphical Notation.

    PubMed

    Jansson, Andreas; Jirstrand, Mats

    2010-05-01

    The Systems Biology Graphical Notation (SBGN) is an emerging standard for graphical notation developed by an international systems biology community. Standardized graphical notation is crucial for efficient and accurate communication of biological knowledge between researchers with various backgrounds in the expanding field of systems biology. Here, we highlight SBGN from a practical point of view and describe how the user can build and simulate SBGN models from a simple drag-and-drop graphical user interface in PathwayLab. Copyright 2010 Elsevier Ltd. All rights reserved.

  2. Conditions for duality between fluxes and concentrations in biochemical networks.

    PubMed

    Fleming, Ronan M T; Vlassis, Nikos; Thiele, Ines; Saunders, Michael A

    2016-11-21

    Mathematical and computational modelling of biochemical networks is often done in terms of either the concentrations of molecular species or the fluxes of biochemical reactions. When is mathematical modelling from either perspective equivalent to the other? Mathematical duality translates concepts, theorems or mathematical structures into other concepts, theorems or structures, in a one-to-one manner. We present a novel stoichiometric condition that is necessary and sufficient for duality between unidirectional fluxes and concentrations. Our numerical experiments, with computational models derived from a range of genome-scale biochemical networks, suggest that this flux-concentration duality is a pervasive property of biochemical networks. We also provide a combinatorial characterisation that is sufficient to ensure flux-concentration duality.The condition prescribes that, for every two disjoint sets of molecular species, there is at least one reaction complex that involves species from only one of the two sets. When unidirectional fluxes and molecular species concentrations are dual vectors, this implies that the behaviour of the corresponding biochemical network can be described entirely in terms of either concentrations or unidirectional fluxes.

  3. Biochemical diagnosis in 3040 kidney stone formers in Argentina.

    PubMed

    Spivacow, Francisco Rodolfo; del Valle, Elisa Elena; Negri, Armando Luis; Fradinger, Erich; Abib, Anabella; Rey, Paula

    2015-08-01

    Nephrolithiasis is a frequent condition in urology that has an important recurrence and high impact in health economy. Knowing the biochemical abnormalities implicated in its pathogenesis is mandatory to establish therapeutic aims. Our objectives are to present the results in 3040 kidney stone formers in Argentina. All patients were selected after completing an ambulatory metabolic protocol with diagnostic purposes. There were 1717 men, (56.48%), with a mean age of 45±12 years, and 1323 women, (43.52%), mean age 44±12 years. 2781 patients had biochemical abnormalities, (91.49%), and were arbitrarily divided in two groups: those who had only one (single) biochemical abnormality (n=2156) and those who had associated abnormalities (n=625). No biochemical abnormalities were found in 259 patients (8.51%). The abnormalities present, single and associated, in order of frequency, were idiopathic hypercalciuria, (56.88%), hyperuricosuria (21.08%), unduly acidic urine (10.95%), hypocitraturia (10.55%), hypomagnesuria (7.9%), primary hyperparathyroidism (3.01%), hyperoxaluria (2.6%), and cystinuria (0.32%). We performed in 484 patient's stone composition and found calcium oxalate stones related to idiopathic hypercalciuria predominantly while uric acid stones to unduly acidic urine. In conclusion, the biochemical abnormalities described are similar to those found in a previous series of our own and to those reported in the literature. Its diagnosis is important to therapeutic purposes to avoid eventual recurrence.

  4. Biochemical characterisation during seed development of oil palm (Elaeis guineensis).

    PubMed

    Kok, Sau-Yee; Namasivayam, Parameswari; Ee, Gwendoline Cheng-Lian; Ong-Abdullah, Meilina

    2013-07-01

    Developmental biochemical information is a vital base for the elucidation of seed physiology and metabolism. However, no data regarding the biochemical profile of oil palm (Elaeis guineensis Jacq.) seed development has been reported thus far. In this study, the biochemical changes in the developing oil palm seed were investigated to study their developmental pattern. The biochemical composition found in the seed differed significantly among the developmental stages. During early seed development, the water, hexose (glucose and fructose), calcium and manganese contents were present in significantly high levels compared to the late developmental stage. Remarkable changes in the biochemical composition were observed at 10 weeks after anthesis (WAA): the dry weight and sucrose content increased significantly, whereas the water content and hexose content declined. The switch from a high to low hexose/sucrose ratio could be used to identify the onset of the maturation phase. At the late stage, dramatic water loss occurred, whereas the content of storage reserves increased progressively. Lauric acid was the most abundant fatty acid found in oil palm seed starting from 10 WAA.

  5. Maximizing the Biochemical Resolving Power of Fluorescence Microscopy

    PubMed Central

    Esposito, Alessandro; Popleteeva, Marina; Venkitaraman, Ashok R.

    2013-01-01

    Most recent advances in fluorescence microscopy have focused on achieving spatial resolutions below the diffraction limit. However, the inherent capability of fluorescence microscopy to non-invasively resolve different biochemical or physical environments in biological samples has not yet been formally described, because an adequate and general theoretical framework is lacking. Here, we develop a mathematical characterization of the biochemical resolution in fluorescence detection with Fisher information analysis. To improve the precision and the resolution of quantitative imaging methods, we demonstrate strategies for the optimization of fluorescence lifetime, fluorescence anisotropy and hyperspectral detection, as well as different multi-dimensional techniques. We describe optimized imaging protocols, provide optimization algorithms and describe precision and resolving power in biochemical imaging thanks to the analysis of the general properties of Fisher information in fluorescence detection. These strategies enable the optimal use of the information content available within the limited photon-budget typically available in fluorescence microscopy. This theoretical foundation leads to a generalized strategy for the optimization of multi-dimensional optical detection, and demonstrates how the parallel detection of all properties of fluorescence can maximize the biochemical resolving power of fluorescence microscopy, an approach we term Hyper Dimensional Imaging Microscopy (HDIM). Our work provides a theoretical framework for the description of the biochemical resolution in fluorescence microscopy, irrespective of spatial resolution, and for the development of a new class of microscopes that exploit multi-parametric detection systems. PMID:24204821

  6. Platform biochemicals for a biorenewable chemical industry.

    PubMed

    Nikolau, Basil J; Perera, M Ann D N; Brachova, Libuse; Shanks, Brent

    2008-05-01

    The chemical industry is currently reliant on a historically inexpensive, petroleum-based carbon feedstock that generates a small collection of platform chemicals from which highly efficient chemical conversions lead to the manufacture of a large variety of chemical products. Recently, a number of factors have coalesced to provide the impetus to explore alternative renewable sources of carbon. Here we discuss the potential impact on the chemical industry of shifting from non-renewable carbon sources to renewable carbon sources. This change to the manufacture of chemicals from biological carbon sources will provide an opportunity for the biological research community to contribute fundamental knowledge concerning carbon metabolism and its regulation. We discuss whether fundamental biological research into metabolic processes at a holistic level, made possible by completed genome sequences and integrated with detailed structural understanding of biocatalysts, can change the chemical industry from being dependent on fossil-carbon feedstocks to using biorenewable feedstocks. We illustrate this potential by discussing the prospect of building a platform technology based upon a concept of combinatorial biosynthesis, which would explore the enzymological flexibilities of polyketide biosynthesis.

  7. Monotone and near-monotone biochemical networks

    PubMed Central

    2007-01-01

    Monotone subsystems have appealing properties as components of larger networks, since they exhibit robust dynamical stability and predictability of responses to perturbations. This suggests that natural biological systems may have evolved to be, if not monotone, at least close to monotone in the sense of being decomposable into a “small” number of monotone components, In addition, recent research has shown that much insight can be attained from decomposing networks into monotone subsystems and the analysis of the resulting interconnections using tools from control theory. This paper provides an expository introduction to monotone systems and their interconnections, describing the basic concepts and some of the main mathematical results in a largely informal fashion. PMID:19003437

  8. Systems biology solutions for biochemical production challenges.

    PubMed

    Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus; Herrgård, Markus J

    2017-06-01

    There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains for biofuels and -chemicals. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Hematologic and plasma biochemical values of Spix's macaws (Cyanopsitta spixii).

    PubMed

    Foldenauer, Ulrike; Borjal, Raffy Jim; Deb, Amrita; Arif, Abdi; Taha, Abid Sharif; Watson, Ryan William; Steinmetz, Hanspeter; Bürkle, Marcellus; Hammer, Sven

    2007-12-01

    The Spix's macaw (Cyanopsitta spixii) is considered the world's most endangered parrot, with the last wild bird disappearing in 2001 and only 74 birds in captivity. To establish hematologic and plasma biochemical reference ranges and to look for differences relative to sex, age, and season, we obtained blood samples from 46 captive Spix's macaws (23 male, 23 female) housed in aviaries at the Al Wabra Wildlife Preservation in the State of Qatar. No significant differences in hematologic or plasma biochemical values were found between females and males. Adult and juvenile birds differed in mean concentrations of glucose, total protein, amylase, cholesterol, and phosphorus; in percentages of heterophils and lymphocytes; and in the absolute lymphocyte count. Total protein, cholesterol, and phosphorus concentrations; hematocrit; and heterophil and lymphocyte counts differed significantly by season. Baseline hematologic and plasma biochemical ranges were established, which may be useful as reference values for clinicians working with this highly endangered species.

  10. Hematologic and plasma biochemical values of hyacinth macaws (Anodorhynchus hyacinthinus).

    PubMed

    Kolesnikovas, Cristiane K M; Niemeyer, Claudia; Teixeira, Rodrigo H F; Nunes, Adauto L V; Rameh-de-Albuquerque, Luciana C; Sant'Anna, Sávio S; Catão-Dias, José L

    2012-09-01

    The hyacinth macaw (Anodorhyncus hyacinthinus), considered the largest psittacine bird species in the world, is an endangered species, with a remaining population of approximately 6500 birds in the wild. To establish hematologic and plasma biochemical reference ranges and to verify differences related to sex, samples from 29 hyacinth macaws (14 males, 15 females) were obtained from birds apprehended from illegal wildlife trade and subsequently housed at the Sorocaba Zoo, Brazil. No significant differences in hematologic or plasma biochemical values were found between females and males. Compared with published reference values, differences were found in mean concentrations of total red blood cell count, corpuscular volume, corpuscular hemoglobin level, total white blood cell count, aspartate aminotransferase level, creatine kinase concentration, alkaline phosphatase concentration, and phosphorus level. Baseline hematologic and plasma biochemical ranges were established, which may be useful as reference values for clinicians working with this endangered species in captivity or rehabilitation centers.

  11. Click Chemistry-Mediated Nanosensors for Biochemical Assays

    PubMed Central

    Chen, Yiping; Xianyu, Yunlei; Wu, Jing; Yin, Binfeng; Jiang, Xingyu

    2016-01-01

    Click chemistry combined with functional nanoparticles have drawn increasing attention in biochemical assays because they are promising in developing biosensors with effective signal transformation/amplification and straightforward signal readout for clinical diagnostic assays. In this review, we focus on the latest advances of biochemical assays based on Cu (I)-catalyzed 1, 3-dipolar cycloaddition of azides and alkynes (CuAAC)-mediated nanosensors, as well as the functionalization of nanoprobes based on click chemistry. Nanoprobes including gold nanoparticles, quantum dots, magnetic nanoparticles and carbon nanomaterials are covered. We discuss the advantages of click chemistry-mediated nanosensors for biochemical assays, and give perspectives on the development of click chemistry-mediated approaches for clinical diagnosis and other biomedical applications. PMID:27217831

  12. Click Chemistry-Mediated Nanosensors for Biochemical Assays.

    PubMed

    Chen, Yiping; Xianyu, Yunlei; Wu, Jing; Yin, Binfeng; Jiang, Xingyu

    2016-01-01

    Click chemistry combined with functional nanoparticles have drawn increasing attention in biochemical assays because they are promising in developing biosensors with effective signal transformation/amplification and straightforward signal readout for clinical diagnostic assays. In this review, we focus on the latest advances of biochemical assays based on Cu (I)-catalyzed 1, 3-dipolar cycloaddition of azides and alkynes (CuAAC)-mediated nanosensors, as well as the functionalization of nanoprobes based on click chemistry. Nanoprobes including gold nanoparticles, quantum dots, magnetic nanoparticles and carbon nanomaterials are covered. We discuss the advantages of click chemistry-mediated nanosensors for biochemical assays, and give perspectives on the development of click chemistry-mediated approaches for clinical diagnosis and other biomedical applications.

  13. Haematological and biochemical variations among eight sighthound breeds.

    PubMed

    Uhríková, I; Lačňáková, A; Tandlerová, K; Kuchařová, V; Řeháková, K; Jánová, E; Doubek, J

    2013-11-01

    The aim of the study was to compare the haematological and biochemical profiles of eight sighthound breeds. Samples were taken from 192 individuals of the sighthound breeds (Whippet, Greyhound, Italian Greyhound, Sloughi, Saluki, Borzoi, Pharaoh Hound and Azawakh). Routine haematological and biochemical examinations were performed and the results were evaluated statistically. There were significant differences in haematology and clinical biochemistry among the sighthound breeds. The most similar laboratory profile to Greyhounds was found in Whippets. Italian Greyhounds had significantly higher alanine aminotransferase activity than other sighthounds, except Pharaoh Hounds. Application of the Greyhound laboratory profile to other sighthounds is not recommended because of the frequent differences in haematological and clinical biochemical reference intervals. © 2013 Australian Veterinary Association.

  14. The origin recognition complex: a biochemical and structural view

    PubMed Central

    Li, Huilin; Stillman, Bruce

    2013-01-01

    The origin recognition complex (ORC) was first discovered in the baker’s yeast in 1992. Identification of ORC opened up a path for subsequent molecular level investigations on how eukaryotic cells initiate and control genome duplication each cell cycle. Twenty years after the first biochemical isolation, ORC is now taking on a three-dimensional shape, although a very blurry shape at the moment, thanks to the recent electron microscopy and image reconstruction efforts. In this chapter, we outline the current biochemical knowledge about ORC from several eukaryotic systems, with emphasis on the most recent structural and biochemical studies. Despite many species-specific properties, an emerging consensus is that ORC is a ATP-dependent machine that recruits other key proteins to form pre-Replicative Complexes (pre-RCs) at many origins of DNA replication, enabling the subsequent initiation of DNA replication in S phase. PMID:22918579

  15. Myocardial biochemical changes in furazolidone-induced cardiomyopathy of turkeys.

    PubMed

    Mirsalimi, S M; Qureshi, F S; Julian, R J; O'Brien, P J

    1990-02-01

    This study tested the hypothesis that membrane transport is the major biochemical system of the myocardium altered in furazolidone-induced cardiomyopathy (round heart disease), before the development of myocardial failure, and that metabolic enzymes and contractile proteins are less affected. Compared with controls, maximal percentage depression of activities of myocardium from furazolidone-treated birds were 40 for creatine kinase, 30 for glycolysis, 30 for glycogen, 20 for myofibrils, 20 for Krebs's cycle enzymes, 15 for fatty acid oxidation and 10 for total soluble protein. Sodium and potassium transport, antioxidant system activity, myosin, myosin isoenzyme patterns and amino acid aminotransferases were unaffected. In marked contrast, the calcium-transport ATPase activity of the sarcoplasmic reticulum had undergone a 60 per cent compensatory increase in activity. The pattern of biochemical changes observed is consistent with a role of ischaemia in the pathogenesis of round heart disease and indicates that calcium transport by the sarcoplasmic reticulum is the major biochemical system affected.

  16. Computer simulation of initial events in the biochemical mechanisms of DNA damage

    NASA Technical Reports Server (NTRS)

    Chatterjee, A.; Holley, W. R.

    1993-01-01

    Understanding the systematic and quantitative correlation between the physical events of energy deposition by ionizing radiation and the ensuing chemical and biochemical processes leading to DNA damage is one of the goals in radiation research. Significant progress has been made toward achieving the stated goal by using theoretical modeling techniques. These techniques are strongly dependent on computer simulation procedures. A review of such techniques with details of various stages of simulation development, including a comparison with available experimental data, is presented in this article.

  17. Techno-Economic Analysis of Bioconversion of Methane into Biofuel and Biochemical (Poster)

    SciTech Connect

    Fei, Q.; Tao, L.; Pienkos, P .T.; Guarnieri, M.; Palou-Rivera, I.

    2014-10-01

    In light of the relatively low price of natural gas and increasing demands of liquid transportation fuels and high-value chemicals, attention has begun to turn to novel biocatalyst for conversion of methane (CH4) into biofuels and biochemicals [1]. A techno-economic analysis (TEA) was performed for an integrated biorefinery process using biological conversion of methane, such as carbon yield, process efficiency, productivity (both lipid and acid), natural gas and other raw material prices, etc. This analysis is aimed to identify research challenges as well provide guidance for technology development.

  18. Advanced biochemical processes for geothermal brines FY 1998 annual operating plan

    SciTech Connect

    1997-10-01

    As part of the overall Geothermal Energy Research which is aimed at the development of economical geothermal resources production systems, the aim of the Advanced Biochemical Processes for Geothermal Brines (ABPGB) effort is the development of economic and environmentally acceptable methods for disposal of geothermal wastes and conversion of by-products to useful forms. Methods are being developed for dissolution, separation and immobilization of geothermal wastes suitable for disposal, usable in inert construction materials, suitable for reinjection into the reservoir formation, or used for recovery of valuable metals.

  19. Wearable technology for bio-chemical analysis of body fluids during exercise.

    PubMed

    Morris, Deirdre; Schazmann, Benjamin; Wu, Yangzhe; Coyle, Shirley; Brady, Sarah; Fay, Cormac; Hayes, Jer; Lau, King Tong; Wallace, Gordon; Diamond, Dermot

    2008-01-01

    This paper details the development of a textile based fluid handling system with integrated wireless biochemical sensors. Such research represents a new advancement in the area of wearable technologies. The system contains pH, sodium and conductivity sensors. It has been demonstrated during on-body trials that the pH sensor has close agreement with measurements obtained using a reference pH probe. Initial investigations into the sodium and conductivity sensors have shown their suitability for integration into the wearable system. It is thought that applications exist in personal health and sports performance and training.

  20. Computer simulation of initial events in the biochemical mechanisms of DNA damage

    NASA Technical Reports Server (NTRS)

    Chatterjee, A.; Holley, W. R.

    1993-01-01

    Understanding the systematic and quantitative correlation between the physical events of energy deposition by ionizing radiation and the ensuing chemical and biochemical processes leading to DNA damage is one of the goals in radiation research. Significant progress has been made toward achieving the stated goal by using theoretical modeling techniques. These techniques are strongly dependent on computer simulation procedures. A review of such techniques with details of various stages of simulation development, including a comparison with available experimental data, is presented in this article.

  1. [Biochemical differentiation of proteus strains from various clinical materials].

    PubMed

    Józefowicz-Piatkowska, H; Woch, G

    1993-01-01

    The material consisted of 729 strain of Proteus isolated from clinical samples in three microbiological laboratories of city of Lódź region. Our of these strains, 466 were Proteus mirabilis, and remaining represented: P. penneri-13 strains, P. vulgaris (II biogroup)-56 and 54 strains which were not classifiable on the basis of biochemical properties and scheme elaborated by Hickman et al. for biogroups of P. vulgaris. The authors indicate feasibility of differentiation of P. vulgaris basing on biochemical tests as a supplementary method to other tests of intracellular differentiation of Proteus.

  2. Biochemical parameters of plants as indicators of air pollution.

    PubMed

    Tripathi, A K; Gautam, Mukesh

    2007-01-01

    In the present study species like Mangifera indica, Linn., Cassia fistula, Linn., and Eucalyptus hybrid were exposed to different air pollution load for short duration (active biomonitoring). Variation in biochemical parameters like chlorophyll, protein, soluble sugar free amino acid, ascorbic acid, nitrate reductase, superoxide dismutase and peroxidase in the leaves were found to be pollution load dependent. These variations can be used as indicators of air pollution for early diagnosis of stress or as a marker for physiological damage to trees prior to the onset of visible injury symptoms. Just by analyzing these biochemical indicators air quality can also be assessed.

  3. Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian patients

    PubMed Central

    Borsatto, Taciane; Sperb-Ludwig, Fernanda; Lima, Samyra E.; S. Carvalho, Maria R.; S. Fonseca, Pablo A.; S. Camelo, José; M. Ribeiro, Erlane; F. V. de Medeiros, Paula; M. Lourenço, Charles; F. M. de Souza, Carolina; Boy, Raquel; Félix, Têmis M.; M. Bittar, Camila; L. C. Pinto, Louise; C. Neto, Eurico; J. Blom, Henk; D. Schwartz, Ida V.

    2017-01-01

    Introduction The association between the BTD genotype and biochemical phenotype [profound biotinidase deficiency (BD), partial BD or heterozygous activity] is not always consistent. This study aimed to investigate the genotype-biochemical phenotype association in patients with low biotinidase activity. Methods All exons, the 5'UTR and the promoter of the BTD gene were sequenced in 72 Brazilian individuals who exhibited low biotinidase activity. For each patient, the expected biochemical phenotype based on the known genotype was compared with the observed biochemical phenotype. Additional non-genetic factors that could affect the biotinidase activity were also analysed. Results Most individuals were identified by neonatal screening (n = 66/72). When consecutive results for the same patient were compared, age, prematurity and neonatal jaundice appeared to affect the level of biotinidase activity. The biochemical phenotype at the time of the second blood collection changed in 11/22 patients compared to results from the first sample. Three novel variants were found: c.1337T>C (p.L446P), c.1466A>G (p.N489S) and c.962G>A (p.W321*). Some patients with the same genotype presented different biochemical phenotypes. The expected and observed biochemical phenotypes agreed in 68.5% of cases (concordant patients). The non-coding variants c.-183G>A, c.-315A>G and c.-514C>T were present in heterozygosis in 5/17 discordant patients. In addition, c.-183G>A and c.-514C>T were also present in 10/37 concordant patients. Conclusions The variants found in the promoter region do not appear to have a strong impact on biotinidase activity. Since there is a disparity between the BTD genotype and biochemical phenotype, and biotinidase activity may be affected by both genetic and non-genetic factors, we suggest that the diagnosis of BD should be based on more than one measurement of plasma biotinidase activity. DNA analysis can be of additional relevance to differentiate between partial BD and

  4. [Biochemical markers of bone metabolism and their importance].

    PubMed

    Obermayer-Pietsch, B; Schwetz, V

    2016-06-01

    Laboratory analyses of biochemical markers for bone and mineral metabolism can play a key role in the assessment of patients with osteoporosis. They may help to assess bone turnover in the diagnostic work-up and aid decision-making as well as selection of pharmaceutical therapy options. Recent publications on therapy response have shown that biochemical markers of bone turnover are valuable tools for the evaluation of therapy success in individual osteoporosis patients and the assessment of bone mineral density gain during therapy.

  5. Behavior and biochemical analysis of phencyclidine

    SciTech Connect

    McCann, D.J.

    1988-01-01

    The objectives of this research were: (1) to develop the radial maze as a tool for the study of phencyclidine (PCP) and related drugs; (2) to evaluate verapamil and colonidine, two proposed treatments for PCP intoxication, as potential antagonists of PCP in the radial maze; and (3) to evaluate the functionality of two distinct types of PCP binding sites as receptors by comparing, for a series of drugs, activity in competitive binding experiments with behavioral activity. The radial maze proved to be a useful tool for the study of PCP and related drugs. With training, rats became highly efficient at obtaining the 8 food pellets placed in the maze. However, PCP and related drugs disrupted this performance, causing numerous reentries into previously visited arms. Results of correlation analyses comparing rank-order affinities with rank-order potencies of (+)SKF-10,047 (the prototypical sigma-opioid agonist), PCP, and several PCP analogs support the involvement of ({sup 3}H)-1-(2-thienyl)cyclohexyl piperidine binding sites (TCP sites) in mediating both the discriminative stimulus properties of PCP and disruption of performance in a 4-arm radial maze.

  6. Overall View of Chemical and Biochemical Weapons

    PubMed Central

    Pitschmann, Vladimír

    2014-01-01

    This article describes a brief history of chemical warfare, which culminated in the signing of the Chemical Weapons Convention. It describes the current level of chemical weapons and the risk of using them. Furthermore, some traditional technology for the development of chemical weapons, such as increasing toxicity, methods of overcoming chemical protection, research on natural toxins or the introduction of binary technology, has been described. In accordance with many parameters, chemical weapons based on traditional technologies have achieved the limit of their development. There is, however, a big potential of their further development based on the most recent knowledge of modern scientific and technical disciplines, particularly at the boundary of chemistry and biology. The risk is even higher due to the fact that already, today, there is a general acceptance of the development of non-lethal chemical weapons at a technologically higher level. In the future, the chemical arsenal will be based on the accumulation of important information from the fields of chemical, biological and toxin weapons. Data banks obtained in this way will be hardly accessible and the risk of their materialization will persist. PMID:24902078

  7. Overall view of chemical and biochemical weapons.

    PubMed

    Pitschmann, Vladimír

    2014-06-04

    This article describes a brief history of chemical warfare, which culminated in the signing of the Chemical Weapons Convention. It describes the current level of chemical weapons and the risk of using them. Furthermore, some traditional technology for the development of chemical weapons, such as increasing toxicity, methods of overcoming chemical protection, research on natural toxins or the introduction of binary technology, has been described. In accordance with many parameters, chemical weapons based on traditional technologies have achieved the limit of their development. There is, however, a big potential of their further development based on the most recent knowledge of modern scientific and technical disciplines, particularly at the boundary of chemistry and biology. The risk is even higher due to the fact that already, today, there is a general acceptance of the development of non-lethal chemical weapons at a technologically higher level. In the future, the chemical arsenal will be based on the accumulation of important information from the fields of chemical, biological and toxin weapons. Data banks obtained in this way will be hardly accessible and the risk of their materialization will persist.

  8. Clinical and biochemical aspects of chromium deficiency.

    PubMed

    Wallach, S

    1985-01-01

    The essentiality of chromium (Cr) in animal and human nutrition is now well accepted. In animals, Cr deficiency can cause a diabetic-like state, impaired growth, elevated blood lipids, increased aortic plaque formation, and decreased fertility and longevity. The ability of Cr to potentiate insulin sensitivity has considerable experimental support. In the human, Cr deficiency has been demonstrated unequivocally in only one clinical situation, patients on total parenteral nutrition without added Cr. In such patients, impaired glucose tolerance, hyperglycemia, relative insulin resistance, peripheral neuropathy, and a metabolic encephalopathy have been noted with reversal of the clinical phenomena by Cr repletion. Many studies have been performed to determine whether Cr deficiency may be important in other clinical conditions, namely, diabetes mellitus, pregnant and parous women, and the aged population. Available data indicate that Cr supplementation can improve glucose metabolism in glucose intolerant individuals and decrease the total/HDL cholesterol ratio regardless of the status of glucose tolerance. However, whether Cr supplementation has long-term health benefits is unknown. Further, despite many tantalizing observations, it is still unclear whether Cr deficiency, latent or overt, is common in any human situation other than generalized malnutrition and total parenteral nutrition without added Cr. Technical uncertainties in the analysis of Cr, Cr contamination of food by the use of stainless steel processing equipment and eating utensils, and the lack of a clinically feasible test for Cr deficiency continue to impede progress in Cr research. Nevertheless, there is considerably more clarity as to plasma and urine Cr levels, food and tissue Cr content, and metabolic pathways of Cr metabolism than existed a decade ago. It is expected that progress will accelerate, since critical questions can now be addressed regarding the role of Cr in human nutrition.

  9. Biochemical and medical importance of vanadium compounds.

    PubMed

    Korbecki, Jan; Baranowska-Bosiacka, Irena; Gutowska, Izabela; Chlubek, Dariusz

    2012-01-01

    Vanadium belongs to the group of transition metals and is present in the air and soil contaminants in large urban agglomerations due to combustion of fossil fuels. It forms numerous inorganic compounds (vanadyl sulfate, sodium metavanadate, sodium orthovanadate, vanadium pentoxide) as well as complexes with organic compounds (BMOV, BEOV, METVAN). Depending on the research model, vanadium compounds exhibit antitumor or carcinogenic properties. Vanadium compounds generate ROS as a result of Fenton's reaction or of the reaction with atmospheric oxygen. They inactivate the Cdc25B(2) phosphatase and lead to degradation of Cdc25C, which induces G(2)/M phase arrest. In cells, vanadium compounds activate numerous signaling pathways and transcription factors, including PI3K-PKB/Akt-mTOR, NF-κB, MEK1/2-ERK, that cause cell survival or increased expression and release of VEGF. Vanadium compounds inhibit p53-dependent apoptosis and promote entry into the S phase of cells containing functional p53 protein. In addition, vanadium compounds, in particular organic derivatives, have insulin-mimetic and antidiabetic properties. Vanadium compounds lower blood glucose levels in animals and in clinical trials. They also inhibit the activity of protein tyrosine phosphatase 1B. By activating the PI3K-PKB/Akt pathway, vanadium compaunds increase the cellular uptake of glucose by the GLUT4 transporter. The PKB/Akt pathway is also used to inactivate glycogen synthase kinase-3. The impact of vanadium compounds on inflammatory reactions has not been fully studied. Vanadium pentoxide causes expression of COX-2 and the release of proinflammatory cytokines in a human lung fibroblast model. Other vanadium compounds activate NF-κB in macrophages by activating IKKβ.

  10. Solving the differential biochemical Jacobian from metabolomics covariance data.

    PubMed

    Nägele, Thomas; Mair, Andrea; Sun, Xiaoliang; Fragner, Lena; Teige, Markus; Weckwerth, Wolfram

    2014-01-01

    High-throughput molecular analysis has become an integral part in organismal systems biology. In contrast, due to a missing systematic linkage of the data with functional and predictive theoretical models of the underlying metabolic network the understanding of the resulting complex data sets is lacking far behind. Here, we present a biomathematical method addressing this problem by using metabolomics data for the inverse calculation of a biochemical Jacobian matrix, thereby linking computer-based genome-scale metabolic reconstruction and in vivo metabolic dynamics. The incongruity of metabolome coverage by typical metabolite profiling approaches and genome-scale metabolic reconstruction was solved by the design of superpathways to define a metabolic interaction matrix. A differential biochemical Jacobian was calculated using an approach which links this metabolic interaction matrix and the covariance of metabolomics data satisfying a Lyapunov equation. The predictions of the differential Jacobian from real metabolomic data were found to be correct by testing the corresponding enzymatic activities. Moreover it is demonstrated that the predictions of the biochemical Jacobian matrix allow for the design of parameter optimization strategies for ODE-based kinetic models of the system. The presented concept combines dynamic modelling strategies with large-scale steady state profiling approaches without the explicit knowledge of individual kinetic parameters. In summary, the presented strategy allows for the identification of regulatory key processes in the biochemical network directly from metabolomics data and is a fundamental achievement for the functional interpretation of metabolomics data.

  11. [Strategies for diagnosis and biochemical control of porphyrias].

    PubMed

    Brock, Axel; Rasmussen, Lars Melholt; Hertz, Jens Michael

    2014-02-17

    Porphyrias are rare, distinct and well characterized diseases due to impairment of one of the eight steps in the biosynthesis of haem, which is the functional group of haemoglobin, myoglobin and cytochromes, including the cytochrome P-450 family. The actual strategies for diagnosis and biochemical control of the five most common porphyrias are described.

  12. Chemical and biochemical thermodynamics: Is it time for a reunification?

    PubMed

    Iotti, Stefano; Raff, Lionel; Sabatini, Antonio

    2017-02-01

    The thermodynamics of chemical reactions in which all species are explicitly considered with atoms and charge balanced is compared with the transformed thermodynamics generally used to treat biochemical reactions where atoms and charges are not balanced. The transformed thermodynamic quantities suggested by Alberty are obtained by execution of Legendre transformation of the usual thermodynamic potentials. The present analysis demonstrates that the transformed values for ΔrG'(0) and ΔrH'(0)can be obtained directly without performing Legendre transformations by simply writing the chemical reactions with all the pseudoisomers explicitly included and charges balanced. The appropriate procedures for computing the stoichiometric coefficients for the pseudoisomers are fully explained by means of an example calculation for the biochemical ATP hydrolysis reaction. It is concluded that the analysis has reunited the "two separate worlds" of conventional thermodynamics and transformed thermodynamics. In addition, it is also shown that the value of the conditional Gibbs energy of reaction, ΔrG', for a biochemical reaction is the same of the value of ΔrG for any chemical reaction involving pseudoisomers of the biochemical reagents.

  13. Biochemical and physiological consequences of the Apollo flight diet.

    NASA Technical Reports Server (NTRS)

    Hander, E. W.; Leach, C. S.; Fischer, C. L.; Rummel, J.; Rambaut, P.; Johnson, P. C.

    1971-01-01

    Six male subjects subsisting on a typical Apollo flight diet for five consecutive days were evaluated for changes in biochemical and physiological status. Laboratory examinations failed to demonstrate any significant changes of the kind previously attributed to weightlessness, such as in serum electrolytes, endocrine values, body fluid, or hematologic parameters.

  14. A MULTILAYER BIOCHEMICAL DRY DEPOSITION MODEL 1. MODEL FORMULATION

    EPA Science Inventory

    A multilayer biochemical dry deposition model has been developed based on the NOAA Multilayer Model (MLM) to study gaseous exchanges between the soil, plants, and the atmosphere. Most of the parameterizations and submodels have been updated or replaced. The numerical integration ...

  15. Metstoich--Teaching Quantitative Metabolism and Energetics in Biochemical Engineering

    ERIC Educational Resources Information Center

    Wong, Kelvin W. W.; Barford, John P.

    2010-01-01

    Metstoich, a metabolic calculator developed for teaching, can provide a novel way to teach quantitative metabolism to biochemical engineering students. It can also introduce biochemistry/life science students to the quantitative aspects of life science subjects they have studied. Metstoich links traditional biochemistry-based metabolic approaches…

  16. Study on color difference estimation method of medicine biochemical analysis

    NASA Astrophysics Data System (ADS)

    Wang, Chunhong; Zhou, Yue; Zhao, Hongxia; Sun, Jiashi; Zhou, Fengkun

    2006-01-01

    The biochemical analysis in medicine is an important inspection and diagnosis method in hospital clinic. The biochemical analysis of urine is one important item. The Urine test paper shows corresponding color with different detection project or different illness degree. The color difference between the standard threshold and the test paper color of urine can be used to judge the illness degree, so that further analysis and diagnosis to urine is gotten. The color is a three-dimensional physical variable concerning psychology, while reflectance is one-dimensional variable; therefore, the estimation method of color difference in urine test can have better precision and facility than the conventional test method with one-dimensional reflectance, it can make an accurate diagnose. The digital camera is easy to take an image of urine test paper and is used to carry out the urine biochemical analysis conveniently. On the experiment, the color image of urine test paper is taken by popular color digital camera and saved in the computer which installs a simple color space conversion (RGB -> XYZ -> L *a *b *)and the calculation software. Test sample is graded according to intelligent detection of quantitative color. The images taken every time were saved in computer, and the whole illness process will be monitored. This method can also use in other medicine biochemical analyses that have relation with color. Experiment result shows that this test method is quick and accurate; it can be used in hospital, calibrating organization and family, so its application prospect is extensive.

  17. [Experiments using rats on Kosmos biosatellites: morphologic and biochemical studies].

    PubMed

    Il'in, E A; Kaplanskiĭ, A S; Savina, E A

    1989-01-01

    Results of morphological and biochemical investigations of rats flown on Cosmos biosatellites are discussed. It is emphasized that most changes occurring during exposure to microgravity are directly or indirectly related to lower musculoskeletal loads which in turn produce deconditioning of different physiological systems and organism as a whole. It is concluded that this deconditioning is associated with both metabolic and structural changes.

  18. Solving the Differential Biochemical Jacobian from Metabolomics Covariance Data

    PubMed Central

    Nägele, Thomas; Mair, Andrea; Sun, Xiaoliang; Fragner, Lena; Teige, Markus; Weckwerth, Wolfram

    2014-01-01

    High-throughput molecular analysis has become an integral part in organismal systems biology. In contrast, due to a missing systematic linkage of the data with functional and predictive theoretical models of the underlying metabolic network the understanding of the resulting complex data sets is lacking far behind. Here, we present a biomathematical method addressing this problem by using metabolomics data for the inverse calculation of a biochemical Jacobian matrix, thereby linking computer-based genome-scale metabolic reconstruction and in vivo metabolic dynamics. The incongruity of metabolome coverage by typical metabolite profiling approaches and genome-scale metabolic reconstruction was solved by the design of superpathways to define a metabolic interaction matrix. A differential biochemical Jacobian was calculated using an approach which links this metabolic interaction matrix and the covariance of metabolomics data satisfying a Lyapunov equation. The predictions of the differential Jacobian from real metabolomic data were found to be correct by testing the corresponding enzymatic activities. Moreover it is demonstrated that the predictions of the biochemical Jacobian matrix allow for the design of parameter optimization strategies for ODE-based kinetic models of the system. The presented concept combines dynamic modelling strategies with large-scale steady state profiling approaches without the explicit knowledge of individual kinetic parameters. In summary, the presented strategy allows for the identification of regulatory key processes in the biochemical network directly from metabolomics data and is a fundamental achievement for the functional interpretation of metabolomics data. PMID:24695071

  19. Development of a new first-aid biochemical detector

    NASA Astrophysics Data System (ADS)

    Hu, Jingfei; Liao, Haiyang; Su, Shilin; Ding, Hao; Liu, Suquan

    2016-10-01

    The traditional biochemical detector exhibits poor adaptability, inconvenient carrying and slow detection, which can't meet the needs of first-aid under field condition like natural or man-made disasters etc. Therefore a scheme of first-aid biochemical detector based on MOMES Micro Spectrometer, UV LED and Photodiode was proposed. An optical detection structure combined continuous spectrum sweep with fixed wavelength measurement was designed, which adopted mobile detection optical path consisting of Micro Spectrometer and Halogen Lamp to detect Chloride (Cl-), Creatinine (Cre), Glucose (Glu), Hemoglobin (Hb). The UV LED and Photodiode were designed to detect Potassium (K-), Carbon dioxide (CO2), Sodium (Na+). According to the field diagnosis and treatment requirements, we designed the embedded control hardware circuit and software system, the prototype of first-aid biochemical detector was developed and the clinical trials were conducted. Experimental results show that the sample's absorbance repeatability is less than 2%, the max coefficient of variation (CV) in the batch repeatability test of all 7 biochemical parameters in blood samples is 4.68%, less than the clinical requirements 10%, the correlation coefficient (R2) in the clinical contrast test with AU5800 is almost greater than 0.97. To sum up, the prototype meets the requirements of clinical application.

  20. MATLAB-Based Teaching Modules in Biochemical Engineering

    ERIC Educational Resources Information Center

    Lee, Kilho; Comolli, Noelle K.; Kelly, William J.; Huang, Zuyi

    2015-01-01

    Mathematical models play an important role in biochemical engineering. For example, the models developed in the field of systems biology have been used to identify drug targets to treat pathogens such as Pseudomonas aeruginosa in biofilms. In addition, competitive binding models for chromatography processes have been developed to predict expanded…

  1. The Stereochemistry of Biochemical Molecules: A Subject to Revisit

    ERIC Educational Resources Information Center

    Centelles, Josep J.; Imperial, Santiago

    2005-01-01

    Although Fischer's convention for stereoisomers is useful for simple molecules, the stereochemistry of complex biochemical molecules is often poorly indicated in textbooks. This article reports on errors in stereochemistry of complex hydrosoluble vitamin B12 molecule. Twenty-five popular biochemistry textbooks were examined for their treatment of…

  2. Physiologic and biochemical aspects of skeletal muscle denervation and reinnervation

    NASA Technical Reports Server (NTRS)

    Max, S. R.; Mayer, R. F.

    1984-01-01

    Some of the physiologic and biochemical changes that occur in mammalian skeletal muscle following denervation and reinnervation are considered and some comparisons are made with changes observed following altered motor function. The nature of the trophic influence by which nerves control muscle properties are discussed, including the effects of choline acetyltransferase and acetylcholinesterase and the role of the acetylcholine receptor.

  3. The biochemical properties of antibodies and their fragments

    USDA-ARS?s Scientific Manuscript database

    Immunoglobulins (Ig) or antibodies are a powerful molecular recognition tools that can be used to identify minute quantities of a given target analyte. Their antigen binding properties define both the sensitivity and selectivity of an immunoassay. Understanding the biochemical properties of this c...

  4. [Interpopulation differeces biochemical adaptation at population of Gorny Altai].

    PubMed

    Chanchaeva, E A; Aĭzman, R I

    2014-01-01

    The factual nutrition of aborigines Russian, altay and kazah nationalities of Gorny Altai were studied. As a result, interpopulating differences of population's nutrition witch quantitative consumption macronutrients have been influence and dependence on the nationality has been determined. Biochemical parameters of blood with quantitative composition of ration's macronutrients are correlated.

  5. Biochemical Parameters of Orienteers Competing in a Long Distance Race.

    ERIC Educational Resources Information Center

    Mikan, Vladimir; And Others

    1992-01-01

    Measured important biochemical parameters in a group of orienteers two hours before beginning and immediately after an orienteering marathon. Found levels of dehydration. Suggests a drinking regimen which is designed for orienteering races. Concludes that no runner having kidney or liver abnormalities or changes in the urine should be allowed to…

  6. BIOCHEMICAL INDICES OF EXPOSURE TO ENVIRONMENTAL ESTROGENS: A SPECIES COMPARISON

    EPA Science Inventory

    Existence of endocrine active substances in the aquatic environment has been clearly established in several studies. Exposure of organisms to both natural and synthetic xenoestrogens have been found to alter biochemical homeostatis and, in some cases, result in reproductive and d...

  7. Metabolic decompensation in methylmalonic aciduria: which biochemical parameters are discriminative?

    PubMed

    Zwickler, Tamaris; Haege, Gisela; Riderer, Alina; Hörster, Friederike; Hoffmann, Georg F; Burgard, Peter; Kölker, Stefan

    2012-09-01

    Recurrent, life-threatening metabolic decompensations often occur in patients with methylmalonic aciduria (MMAuria). Our study evaluated (impending) metabolic decompensations in these patients aiming to identify the most frequent and reliable clinical and biochemical abnormalities that could be helpful for decision-making on when to start an emergency treatment. Seventy-six unscheduled and 179 regular visits of 10 patients with confirmed MMAuria continuously followed by our metabolic centre between 1975 and 2009 were analysed. The most frequent symptom of an impending acute metabolic decompensation was vomiting (90% of episodes), whereas symptoms of intercurrent infectious disease (29%) or other symptoms (such as food refusal and impaired consciousness) were found less often. Thirty-five biochemical parameters were included in the analysis. Among them, pathological changes of acid-base balance reflecting metabolic acidosis with partial respiratory compensation (decreased pH, pCO(2), standard bicarbonate, and base excess) and elevated ammonia were the most reliable biochemical parameters for the identification of a metabolic decompensation and the estimation of its severity. In contrast, analyses of organic acids, acylcarnitines and carnitine status were less discriminative. In conclusion, careful history taking and identification of suspicious symptoms in combination with a small number of rapidly available biochemical parameters are helpful to differentiate compensated metabolic condition and (impending) metabolic crisis and to decide when to start an emergency treatment.

  8. Biochemical and Structural Studies of RNA Modification and Repair

    ERIC Educational Resources Information Center

    Chan, Chio Mui

    2009-01-01

    RNA modification, RNA interference, and RNA repair are important events in the cell. This thesis presents three projects related to these three fields. By using both biochemical and structural methods, we characterized enzymatic activities of pseudouridine synthase TruD, solved the structure of "A. aeolicus" GidA, and reconstituted a novel…

  9. Molecular and Biochemical Characterization of Postharvest Senescence in Broccoli

    PubMed Central

    Page, Tania; Griffiths, Gareth; Buchanan-Wollaston, Vicky

    2001-01-01

    Postharvest senescence in broccoli (Brassica oleracea L. var Italica) florets results in phenotypic changes similar to those seen in developmental leaf senescence. To compare these two processes in more detail, we investigated molecular and biochemical changes in broccoli florets stored at two different temperatures after harvest. We found that storage at cooler temperatures delayed the symptoms of senescence at both the biochemical and gene expression levels. Changes in key biochemical components (lipids, protein, and chlorophyll) and in gene expression patterns occurred in the harvested tissue well before any visible signs of senescence were detected. Using previously identified senescence-enhanced genes and also newly isolated, differentially expressed genes, we found that the majority of these showed a similar enhancement of expression in postharvest broccoli as in developmental leaf senescence. At the biochemical level, a rapid loss of membrane fatty acids was detected after harvest, when stored at room temperature. However, there was no corresponding increase in levels of lipid peroxidation products. This, together with an increased expression of protective antioxidant genes, indicated that, in the initial stages of postharvest senescence, an orderly dismantling of the cellular constituents occurs, using the available lipid as an energy source. Postharvest changes in broccoli florets, therefore, show many similarities to the processes of developmental leaf senescence. PMID:11161029

  10. Classic and contemporary approaches to modeling biochemical reactions

    PubMed Central

    Chen, William W.; Niepel, Mario; Sorger, Peter K.

    2010-01-01

    Recent interest in modeling biochemical networks raises questions about the relationship between often complex mathematical models and familiar arithmetic concepts from classical enzymology, and also about connections between modeling and experimental data. This review addresses both topics by familiarizing readers with key concepts (and terminology) in the construction, validation, and application of deterministic biochemical models, with particular emphasis on a simple enzyme-catalyzed reaction. Networks of coupled ordinary differential equations (ODEs) are the natural language for describing enzyme kinetics in a mass action approximation. We illustrate this point by showing how the familiar Briggs-Haldane formulation of Michaelis-Menten kinetics derives from the outer (or quasi-steady-state) solution of a dynamical system of ODEs describing a simple reaction under special conditions. We discuss how parameters in the Michaelis-Menten approximation and in the underlying ODE network can be estimated from experimental data, with a special emphasis on the origins of uncertainty. Finally, we extrapolate from a simple reaction to complex models of multiprotein biochemical networks. The concepts described in this review, hitherto of interest primarily to practitioners, are likely to become important for a much broader community of cellular and molecular biologists attempting to understand the promise and challenges of “systems biology” as applied to biochemical mechanisms. PMID:20810646

  11. A MULTILAYER BIOCHEMICAL DRY DEPOSITION MODEL 2. MODEL EVALUATION

    EPA Science Inventory

    The multilayer biochemical dry deposition model (MLBC) described in the accompanying paper was tested against half-hourly eddy correlation data from six field sites under a wide range of climate conditions with various plant types. Modeled CO2, O3, SO2<...

  12. Biochemical Parameters of Orienteers Competing in a Long Distance Race.

    ERIC Educational Resources Information Center

    Mikan, Vladimir; And Others

    1992-01-01

    Measured important biochemical parameters in a group of orienteers two hours before beginning and immediately after an orienteering marathon. Found levels of dehydration. Suggests a drinking regimen which is designed for orienteering races. Concludes that no runner having kidney or liver abnormalities or changes in the urine should be allowed to…

  13. Metstoich--Teaching Quantitative Metabolism and Energetics in Biochemical Engineering

    ERIC Educational Resources Information Center

    Wong, Kelvin W. W.; Barford, John P.

    2010-01-01

    Metstoich, a metabolic calculator developed for teaching, can provide a novel way to teach quantitative metabolism to biochemical engineering students. It can also introduce biochemistry/life science students to the quantitative aspects of life science subjects they have studied. Metstoich links traditional biochemistry-based metabolic approaches…

  14. The Stereochemistry of Biochemical Molecules: A Subject to Revisit

    ERIC Educational Resources Information Center

    Centelles, Josep J.; Imperial, Santiago

    2005-01-01

    Although Fischer's convention for stereoisomers is useful for simple molecules, the stereochemistry of complex biochemical molecules is often poorly indicated in textbooks. This article reports on errors in stereochemistry of complex hydrosoluble vitamin B12 molecule. Twenty-five popular biochemistry textbooks were examined for their treatment of…

  15. Annelid Aminotransferase Activity--An Exercise in Basic Biochemical Skills.

    ERIC Educational Resources Information Center

    Teal, A. R.; Alcock, R. S.

    1978-01-01

    A practical exercise is described that allows students to investigate a specific problem using a variety of biochemical techniques. The need for a thorough understanding of the theoretical principles underlying these processes is emphasized. A program of private study and assessment is suggested to enable the progress of students to be followed.…

  16. The use of biochemical methods in extraterrestrial life detection

    NASA Astrophysics Data System (ADS)

    McDonald, Gene

    2006-08-01

    Instrument development for in situ extraterrestrial life detection focuses primarily on the ability to distinguish between biological and non-biological material, mostly through chemical analysis for potential biosignatures (e.g., biogenic minerals, enantiomeric excesses). In constrast, biochemical analysis techniques commonly applied to Earth life focus primarily on the exploration of cellular and molecular processes, not on the classification of a given system as biological or non-biological. This focus has developed because of the relatively large functional gap between life and non-life on Earth today. Life on Earth is very diverse from an environmental and physiological point of view, but is highly conserved from a molecular point of view. Biochemical analysis techniques take advantage of this similarity of all terrestrial life at the molecular level, particularly through the use of biologically-derived reagents (e.g., DNA polymerases, antibodies), to enable analytical methods with enormous sensitivity and selectivity. These capabilities encourage consideration of such reagents and methods for use in extraterrestrial life detection instruments. The utility of this approach depends in large part on the (unknown at this time) degree of molecular compositional differences between extraterrestrial and terrestrial life. The greater these differences, the less useful laboratory biochemical techniques will be without significant modification. Biochemistry and molecular biology methods may need to be "de-focused" in order to produce instruments capable of unambiguously detecting a sufficiently wide range of extraterrestrial biochemical systems. Modern biotechnology tools may make that possible in some cases.

  17. Light-addressable potentiometric sensor for biochemical systems

    NASA Astrophysics Data System (ADS)

    Hafeman, Dean G.; Parce, J. Wallace; McConnell, Harden M.

    1988-05-01

    Numerous biochemical reactions can be measured potentiometrically through changes in pH, redox potential, or transmembrane potential. An alternating photocurrent through an electrolyte-insulator-semiconductor interface provides a highly sensitive means to measure such potential changes. A spatially selectable photoresponse permits the determination of a multiplicity of chemical events with a single semiconductor device.

  18. [Biochemical characteristics of the causative agent of fowl typhoid].

    PubMed

    Giurov, B

    1986-01-01

    Studied were the biochemical properties of a total of 563 Salmonella strains divided into two biotypes--S. gallinarum (542) and S. pullorum (21). The first ones were isolated from typhoid foci of chickens, poults, turkeys, pheasants, guinea fowls, pigeons, and starlings that had died of septicaemia. One strain was isolated from a 4-month-old pig. The S. pullorum strains originated from epizootiologically linked foci of pullorosis, being isolated from live chicken carriers, dead embryos, and down from hatcheries as well as from young chickens that had died in them up to the age of 20 days. The link is discussed between the biochemical properties of the isolated strains and their origin, and the importance of some biochemical tests employed to distinguished them. Attention is paid to the likeliness of isolating aberant strains of S. gallinarum with deviations from the morphology of colonies and their antigenic and biochemical characteristic typical of the species. Suggested is the employment of the tests for motility, dulcit, maltosa, ramnosa, sorbit, and ornithine for the rapid differentiation of Salmonella gallinarum from the closely related Salmonella species of D serologic group. In order to avoid the occurrence of confusion with other microbial species the tests for the demonstration of lactose, sodium malonate, phenylalanine, indole, hydrogen sulfide, and lysine-decarboxylase.

  19. Biochemical and Structural Studies of RNA Modification and Repair

    ERIC Educational Resources Information Center

    Chan, Chio Mui

    2009-01-01

    RNA modification, RNA interference, and RNA repair are important events in the cell. This thesis presents three projects related to these three fields. By using both biochemical and structural methods, we characterized enzymatic activities of pseudouridine synthase TruD, solved the structure of "A. aeolicus" GidA, and reconstituted a novel…

  20. Opium and heroin alter biochemical parameters of human's serum.

    PubMed

    Kouros, Divsalar; Tahereh, Haghpanah; Mohammadreza, Afarinesh; Minoo, Mahmoudi Zarandi

    2010-05-01

    Iran is a significant consumer of opium, and, generally, of opioids, in the world. Addiction is one of the important issues of the 21st century and is an imperative issue in Iran. Long-term consumption of opioids affects homeostasis. To determine the effects of opium and heroin consumption on serum biochemical parameters. In a cross-sectional study, subjects who had consumed heroin (n = 35) or opium (n = 42) for more than two years and 35 nonaddict volunteers as the control group were compared in regard to various biochemical parameters such as fasting blood sugar (FBS), Na(+), K(+), Ca(2+), blood urea nitrogen (BUN), uric acid (UA), triglyceride (TG), cholesterol, creatinine, and total protein. Chromatography was used to confirm opioid consumption, and the concentration of biochemical parameters was determined by laboratory diagnostic tests on serum. No significant differences were found in Na(+), Ca(2+), BUN, UA, TG, creatinine, and total protein concentrations among the three groups. FBS, K(+), and UA levels were significantly lower in opium addicts compared to the control group. Serum Ca(2+) concentration of heroin addicts showed a significant decrease compared to that of the control group. Both addict groups showed a significant decrease in serum cholesterol levels. Chronic use of opium and heroin can change serum FBS, K(+), Ca(2+), UA, and cholesterol. This study, one of few on the effects of opium on serum biochemical parameters in human subjects, has the potential to contribute to the investigation of new approaches for further basic studies.