The Biology of Beggiatoa.

Part I. An accurate most-probable-number enumeration method was developed for counting the number of Beggiatoa trichomes from various freshwater sediments. The medium consisted of extracted hay, diluted soil extract, 0.05% sodium acetate, and 15-35 units per ml of catalase. The same enrichment medium, but without the acetate, was the best enrichment medium from which to obtain pure cultures. A total of thirty-two strains of Beggiatoa were isolated from seven different freshwater habitats and were separated into five groups based on several preliminary characteristics. Four of the groups contained cells with trichomes of approximately the same diameter (1.5-2.7 (mu)m) and may be B. leptomitiformis or an unnamed species. The fifth group appeared to be B. alba. With the exception of three strains, all of the strains deposited sulfur in the presence of hydrogen sulfide. All of the strains grew heterotrophically and deposited poly-(beta)-hydroxybutyrate and volutin when grown on acetate supplemented with low concentrations of other organic nutrients. Thin sections of sulfur bearing trichomes indicated that the sulfur granules were external to the cytoplasmic membrane and were surrounded by an additional membrane. Part II. The assimilation and metabolism of CO(,2) by Beggiatoa alba strain B18LD was investigated. Although B. alba was shown to require CO(,2) for growth, the addition of excess CO(,2) (as NaHCO(,3)) to the medium in a closed system did not stimulate growth. The K(,m) values for the CO(,2) assimilation by heterotrophically-grown and mixotrophically-grown cells were 297 (mu)M and 666 (mu)M, respectively. The high K(,m) values for CO(,2) assimilation, coupled with acetate oxidation data suggested that the required CO(,2) was endogenously produced from acetate. The first stable fixation products from CO(,2) assimilation were aspartate and glutamate. Carbon dioxide was incorporated into cell wall material, proteins, nucleic acids, and amino acids and organic acids, but not into poly-(beta)-hydroxybutyrate. Fluoroacetate and glyoxylate inhibited CO(,2) assimilation. The CO(,2) fixation enzymes isocitrate dehydrogenase (NADP; reversed) and malate dehydrogenase (NADP; decarboxylating) were found in cell-free extracts of both mixotrophically-grown and heterotrophically-grown cells. The results suggested that an incomplete reductive tricarboxylic acid cycle might be present in B. alba for the metabolism of CO(,2). Part III. The assimilation and oxidation of (\u2714)C-1- and (\u2714)C-2- acetate by several strains of Beggiatoa were investigated. Approximately 16-28% of the (\u2714)C-2-acetate and 28-46% of the carboxyl labeled acetate were oxidized to (\u2714)CO(,2). The apparent K(,m) for the combined assimilation and oxidation of (\u2714)C-2-acetate by Beggiatoa alba B18LD was 1.0-1.4 (mu)M under differing growth conditions. Sixty-one to 73% of the (\u2714)C-1- or (\u2714)C-2- acetate assimilated by washed trichomes was incorporated into lipid, whereas 55% of the assimilated (\u2714)C-1-acetate was incorporated into poly-(beta)-hydroxybutyrate (PHB). That corresponded with chemical data showing that 56% of the cell dry weight was PHB. Fluoroacetate inhibited (\u2714)C-1-acetate assimilation at concentrations of 100-1000 (mu)M but inhibited (\u2714)C-1-acetate oxidation to (\u2714)CO(,2) only at 1000 (mu)M. After a 5 sec incubation of B. alba with (\u2714)C-1-acetate, the major products were succinate (39.7%), glutamate (11.1%), and fumarate (8.9%); after 25 sec, succinate (42.3%), glutamate (15.7%), and hydroxybutyrate (11.5%) were the major intermediates observed. The results indicated that a functional glyoxylate bypass might be present, but that citrate formation via the condensing enzyme was not present

Common variants in P2RY11 are associated with narcolepsy.

l e t t e r s Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genomewide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Americans). We identify a SNP in the 3′ untranslated region of P2RY11, the purinergic receptor subtype P2Y 11 gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 × 10 −10 , odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The diseaseassociated allele is correlated with reduced expression of P2RY11 in CD8 + T lymphocytes (339% reduced, P = 0.003) and natural killer (NK) cells (P = 0.031), but not in other peripheral blood mononuclear cell types. The low expression variant is also associated with reduced P2RY11-mediated resistance to ATP-induced cell death in T lymphocytes (P = 0.0007) and natural killer cells (P = 0.001). These results identify P2RY11 as an important regulator of immune-cell survival, with possible implications in narcolepsy and other autoimmune diseases

Common variants in P2RY11 are associated with narcolepsy.

Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genome-wide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Americans). We identify a SNP in the 3' untranslated region of P2RY11, the purinergic receptor subtype P2Y₁₁ gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 × 10⁻¹⁰, odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The disease-associated allele is correlated with reduced expression of P2RY11 in CD8(+) T lymphocytes (339% reduced, P = 0.003) and natural killer (NK) cells (P = 0.031), but not in other peripheral blood mononuclear cell types. The low expression variant is also associated with reduced P2RY11-mediated resistance to ATP-induced cell death in T lymphocytes (P = 0.0007) and natural killer cells (P = 0.001). These results identify P2RY11 as an important regulator of immune-cell survival, with possible implications in narcolepsy and other autoimmune diseases.journal articleresearch support, n.i.h., extramuralresearch support, non-u.s. gov'tresearch support, u.s. gov't, p.h.s.2011 Jan2010 12 19importedErratum in : Nat Genet. 2011 Oct;43(10):1040

Studies on the modification, by various agents, of the heat sensitivity of poliovirus

The decrease in heat sensitivity of Poliovirus, Type I, after incubation with cystine, has been studied. Characteristics of the inactivation by heat have also been studied. The results have led to an hypothesis which, while in no way completely satisfactory, provides a useful picture by which the data can be discussed, and also serves to indicate the areas to be clarified by future experiments. This hypothesis proposes the existence of two reactivity classes of viral sulfhydryl groups: -SH groups of the first class are oxidized by oxygen and by iodosobenzoic acid, probably to disulfides: -SH groups of the second class are so situated as to be unable to form disulfide bonds readily, and thus cannot be oxidized by oxygen, but can be oxidized to -SO2H or –SO3H by iodosobenzoic acid. The inactivation is postulated to consist of at least two steps: oxidation of sulfhydryl group(s), followed by denaturation of the viral protein. The existence of a denaturation step is suggested by the calculation of an Arrhenius constant for aerobic inactivation of 76,000 calories/mole. Evidence is presented to indicate that, at least in the case of oxidation by iodosobenzoate, the oxidation has a sensitizing effect; i.e., it increases the probability for the denaturation to occur. The main requirement for stabilization appears to be the formation of a disulfide bond between a half cystine molecule and the viral -SH group. No compound has been found to produce stabilization as complete as L-cystine. The results suggest that the other compounds tested do not react with the viral -SH groups, and therefore one cannot decide whether formation of disulfide bonds with a stabilizing compound is in itself sufficient for stabilization. This does indicate, however, that the -SH groups must occur in an extremely stereo-specific environmen

Bispecific T-Cell Redirection versus Chimeric Antigen Receptor (CAR)-T Cells as Approaches to Kill Cancer Cells

The concepts for T-cell redirecting bispecific antibodies (TRBAs) and chimeric antigen receptor (CAR)-T cells are both at least 30 years old but both platforms are just now coming into age. Two TRBAs and two CAR-T cell products have been approved by major regulatory agencies within the last ten years for the treatment of hematological cancers and an additional 53 TRBAs and 246 CAR cell constructs are in clinical trials today. Two major groups of TRBAs include small, short-half-life bispecific antibodies that include bispecific T-cell engagers (BiTE®s) which require continuous dosing and larger, mostly IgG-like bispecific antibodies with extended pharmacokinetics that can be dosed infrequently. Most CAR-T cells today are autologous, although significant strides are being made to develop off-the-shelf, allogeneic CAR-based products. CAR-Ts form a cytolytic synapse with target cells that is very different from the classical immune synapse both physically and mechanistically, whereas the TRBA-induced synapse is similar to the classic immune synapse. Both TRBAs and CAR-T cells are highly efficacious in clinical trials but both also present safety concerns, particularly with cytokine release syndrome and neurotoxicity. New formats and dosing paradigms for TRBAs and CAR-T cells are being developed in efforts to maximize efficacy and minimize toxicity, as well as to optimize use with both solid and hematologic tumors, both of which present significant challenges such as target heterogeneity and the immunosuppressive tumor microenvironment

Enumeration, Isolation, and Characterization of Beggiatoa from Freshwater Sediments

An accurate most-probable-number enumeration method was developed for counting the number of Beggiatoa trichomes from various freshwater sediments. The medium consisted of extracted hay, diluted soil extract, 0.05% acetate, and 15 to 35 U of catalase per ml. The same enrichment medium, but without the acetate, was the best enrichment medium from which to obtain pure cultures because it supported good growth of the beggiatoas without allowing them to be overgrown by other bacteria. A total of 32 strains of Beggiatoa were isolated from seven different freshwater habitats and partially characterized. The strains were separated into five groups based on several preliminary characteristics. Four of the groups contained cells with trichomes of approximately the same diameter (1.5 to 2.7 μm) and may be Beggiatoa leptomitiformis or an unnamed species. The fifth group appeared to be Beggiatoa alba. With the exception of three strains, all of the strains deposited sulfur in the presence of hydrogen sulfide, and all strains grew heterotrophically and deposited poly-β-hydroxybutyrate and volutin when grown on acetate supplemented with low concentrations of other organic nutrients. Thin sections of sulfur-bearing trichomes indicated that the sulfur granules were external to the cytoplasmic membrane and that they were surrounded by an additional membrane

A General Purpose Military Satellite Communications System Concept

International Telemetering Conference Proceedings / October 14-16, 1980 / Bahia Hotel, San Diego, CaliforniaAn interoperable military satellite communications system concept involving proliferated, all-frequency band, microprocessor-controlled satellites is proposed. Network access and control techniques are suggested, and the utility and cost effectiveness in terms of terminal cost savings are explored.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection