Anthrax Research Today is a free monthly online journal that collates and summarizes the latest research about Anthrax, including details on bacillus anthracis, contagiousness, exposure, effects.

Function, structure and regulation of the vacuolar (H(+))-ATPases.

Jefferies KC, Cipriano DJ, Forgac M

The vacuolar ATPases (or V-ATPases) are ATP-driven proton pumps that function to both acidify intracellular compartments and to transport protons across the plasma membrane. Intracellular V-ATPases function in such normal cellular processes as receptor-mediated endocytosis, intracellular membrane traffic, prohormone processing, protein degradation and neurotransmitter uptake, as well as in disease processes, including infection by influenza and other viruses and killing of cells by anthrax and diphtheria toxin. Plasma membrane V-ATPases are important in such physiological processes as urinary acidification, bone resorption and sperm maturation as well as in human diseases, including osteopetrosis, renal tubular acidosis and tumor metastasis. V-ATPases are large multi-subunit complexes composed of a peripheral domain (V(1)) responsible for hydrolysis of ATP and an integral domain (V(0)) that carries out proton transport. Proton transport is coupled to ATP hydrolysis by a rotary mechanism. V-ATPase activity is regulated in vivo using a number of mechanisms, including reversible dissociation of the V(1) and V(0) domains, changes in coupling efficiency of proton transport and ATP hydrolysis and changes in pump density through reversible fusion of V-ATPase containing vesicles. V-ATPases are emerging as potential drug targets in treating a number of human diseases including osteoporosis and cancer.

Published 1 May 2008 in Arch Biochem Biophys.
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Articles on Anthrax published 29 April 2008:

Molecular epidemiology of Bacillus anthracis: determining the correct origin.   Appl Environ Microbiol, 74(9): 2928-31.

We analyzed and compared strains of Bacillus anthracis isolated from husbandry and industrial anthrax cases in Switzerland between 1952 and 1981 with published data using multiple-locus variable-number tandem repeat analysis. Strains isolated from autochthonous cases of anthrax in cattle belong to genotype B2, together with strains from continental Europe, while human B. anthracis strains clustered with genotype A4. These strains could be traced back to outbreaks of human anthrax that occurred ... [Abstract] [Full-text]

Improvement of an antibody neutralizing the anthrax toxin by simultaneous mutagenesis of its six hypervariable loops.   J Mol Biol, 378(5): 1094-103.

The enhancement of antibody affinity by mutagenesis targeting only complementarity determining regions has the advantage of respecting the framework regions, which are important for tolerance if clinical use is envisaged. Here, starting from a Fab (antigen-binding fragment; 35PA(83)) capable of neutralizing the lethal toxin of anthrax and having an affinity of 3.4 nM for its antigen, a phage-displayed library of variants where all six complementarity determining regions (73 positions) were ... [Abstract] [Full-text]

Articles on Anthrax published 23 April 2008:

Antiinflammatory cAMP signaling and cell migration genes co-opted by the anthrax bacillus.   Proc Natl Acad Sci U S A, 105(16): 6150-5.

Bacillus anthracis, the etiologic agent of anthrax, avoids immune surveillance and commandeers host macrophages as a vehicle for lymphatic spreading. Here, we show that B. anthracis edema toxin (ET), via its adenylyl cyclase activity, dramatically increases the motility of infected macrophages and the expression of vascular endothelial growth factor. The transcription factor CREB and the syndecan-1 gene, a CREB target, play crucial roles in ET-induced macrophage migration. These molecular and ... [Abstract] [Full-text]

Articles on Anthrax published 22 April 2008:

Liberty to Decide on Dual Use Biomedical Research: An Acknowledged Necessity.   Sci Eng Ethics.

Humanity entered the twenty-first century with revolutionary achievements in biomedical research. At the same time multiple "dual-use" results have been published. The battle against infectious diseases is meeting new challenges, with newly emerging and re-emerging infections. Both natural disaster epidemics, such as SARS, avian influenza, haemorrhagic fevers, XDR and MDR tuberculosis and many others, and the possibility of intentional mis-use, such as letters containing anthrax ... [Abstract] [Full-text]

Articles on Anthrax published 21 April 2008:

Enhancement of antibody responses to Bacillus anthracis protective antigen domain IV by use of calreticulin as a chimeric molecular adjuvant.   Infect Immun, 76(5): 1952-9.

The generation of protective humoral immune responses against the receptor-binding domain (domain IV) of protective antigen [PA(dIV)] of Bacillus anthracis represents a plausible approach against anthrax toxin. In the current study, we have developed a naked DNA vaccine encoding calreticulin (CRT) linked to PA(dIV) of Bacillus anthracis [CRT/PA(dIV)]. We transfected a human embryonic kidney cell line (HEK 293) with CRT/PA(dIV) DNA and performed Western blotting and confocal microscopy analysis. ... [Abstract] [Full-text]

Renewable enzyme reactors based on beds of artificial gel antibodies.   J Biochem Biophys Methods, 70(6): 1188-91.

A novel approach is described for the synthesis of beds for enzyme reactors. The method is based on the use of artificial antibodies in the form of polyacrylamide gel particles with diameters around 0.1-0.3 mm. These gel particles mimic protein antibodies, raised in experimental animals, in the sense that they selectively recognize and adsorb only the protein present during the preparation of the "antibodies". The gel antibodies have several advantages over conventional protein ... [Abstract] [Full-text]

Mast cell activators: a new class of highly effective vaccine adjuvants.   Nat Med.

Mast cells (MCs) have recently received recognition as prominent effectors in the regulation of immune cell migration to draining lymph nodes and lymphocyte activation. However, their role in the development of humoral immune responses is not clear. Here, we demonstrate that subcutaneous or nasal administration of small-molecule MC activators with vaccine antigens evokes large increases in antigen-specific serum immunoglobulin G (IgG) responses. These responses were MC dependent and correlated ... [Abstract] [Full-text]

Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury.   Cell, 133(2): 235-49.

Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via ... [Abstract] [Full-text]

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