Disruption of ER-mitochondria tethering and signalling in C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia.

Hexanucleotide repeat expansions in C9orf72 are the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The mechanisms by which the expansions cause disease are not properly understood but a favoured route involves its translation into dipeptide repeat (DPR) polypeptides, some of which are neurotoxic. However, the precise targets for mutant C9orf72 and DPR toxicity are not fully clear, and damage to several neuronal functions has been described.

Helix pomatia hemocyanin - a novel bio-adjuvant for viral and bacterial antigens.

Background: New generated subunit vaccines are characterized by increased safety and lack of side effects, however they suffer from weak immunogenicity. The adjuvants are substances that have the ability to enhance the magnitude and duration of the immune response and to increase vaccine efficacy, but the different vaccines may require diverse adjuvants. The urgent need of novel adjuvant formulations occurs, thus ensuring protective cellular and humoral responses against infectious pathogens.

Anti-cancer properties of gastropodan hemocyanins in murine model of colon carcinoma.

Background: Various immunotherapeutic approaches have been used for the treatment of cancer. A number of natural compounds are designed to repair, stimulate, or enhance the immune system response. Among them are the hemocyanins (Hcs) - extracellular copper proteins isolated from different arthropod and mollusc species.

Suppression of dsDNA-specific B lymphocytes reduces disease symptoms in SCID model of mouse lupus.

Self-specific B cells play a main role in the pathogenesis of lupus. This autoimmune disease is characterized by the generation of autoantibodies against self antigens, and the elimination of B and T cells involved in the pathological immune response is a logical approach for effective therapy. We have previously constructed a chimeric molecule by coupling a DNA-mimotope peptides to an anti-CD32 antibody.

Targeted silencing of DNA-specific B cells combined with partial plasma cell depletion displays additive effects on delaying disease onset in lupus-prone mice.

Targeting autoreactive B lymphocytes at any stage of their differentiation could yield viable therapeutic strategies for treating autoimmunity. All currently used drugs, including the most recently introduced biological agents, lack target specificity. Selective silencing of double-stranded DNA-specific B cells in animals with spontaneous lupus has been achieved previously by the administration of a chimeric antibody molecule that cross-links their DNA-reactive B cell immunoglobulin receptors with inhibitory FcγIIb (CD32) receptors.

Generation of gene-engineered chimeric DNA molecules for specific therapy of autoimmune diseases.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the development of self-reactive B and T cells and autoantibody production. In particular, double-stranded DNA-specific B cells play an important role in lupus progression, and their selective elimination is a reasonable approach for effective therapy of SLE. DNA-based vaccines aim at the induction of immune response against the vector-encoded antigen.

Production of enzymes and antimicrobial compounds by halophilic Antarctic Nocardioides sp. grown on different carbon sources.

This study demonstrated the potential of microbial isolates from Antarctic soils to produce hydrolytic enzymes by using specific substrates. The results revealed potential of the strains to produce a broad spectrum of hydrolytic enzymes. Strain A-1 isolated from soil samples in Casey Station, Wilkes Land, was identified as Nocardioides sp.

Marine gastropod hemocyanins as adjuvants of non-conjugated bacterial and viral proteins.

Killed viral vaccines and bacterial toxoids are weakly immunogenic. Numerous compounds are under evaluation as immunological adjuvants and peptide-carriers to improve the immune response. The hemocyanins, giant extracellular copper proteins in the blood of many mollusks, are widely used as immune stimulants.

Target silencing of disease-associated B-lymphocytes by chimeric molecules in SCID model of pristane-induced autoimmunity.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the generation of autoantibodies against a diverse array of self-antigens. The B cells producing immunoglobulin G (IgG) antibodies to double-stranded DNA appear to play a main role in the disease progression. Their specific elimination is a reasonable mechanism for effective therapy of SLE.

Re-establishing tolerance to DNA in humanized and murine models of SLE.

DNA-specific B cells in SLE represent a logical target for therapeutic intervention. We hypothesize that it is possible to re-establish tolerance to native DNA in SCID mice with cells transferred from SLE patients or from lupus-prone MRL/lpr mice by administering chimeric molecules, containing a monoclonal antibody against inhibitory B cell receptors coupled to a peptide that antigenically mimics DNA. These protein-engineered molecules are able to co-crosslink selectively the antigen receptors of B cells possessing anti-native DNA specificity with the inhibitory surface receptors, thus delivering a strong suppressive signal.

Biosurfactant production by halotolerant Rhodococcus fascians from Casey Station, Wilkes Land, Antarctica.

Isolate A-3 from Antarctic soil in Casey Station, Wilkes Land, was characterized for growth on hydrocarbons. Use of glucose or kerosene as a sole carbon source in the culture medium favoured biosynthesis of surfactant which, by thin-layer chromatography, indicated the formation of a rhamnose-containing glycolipid. This compound lowered the surface tension at the air/water interface to 27 mN/m as well as inhibited the growth of B.

Optimization of the production medium for biosynthesis of antifungal antibiotic AK-111-81 by phosphate-deregulated mutant of Streptomyces hygroscopicus.

Experimental mathematical designs were applied for optimization of a nutrient medium for biosynthesis of the antifungal antibiotic AK-111-81 by phosphate-deregulated mutant of Streptomyces hygroscopicus 111-81. Antifungal antibiotic AK-111-81 possesses well-expressed activity against Fusarium graminearum and other phytopathogenic fungi. The level of the production of the antibiotic AK-111-81 on this medium is more than three times higher than on the initial medium.

Spontaneous white sectored-mutants in Streptomyces hygroscopicus 111-81: characterization and antibiotic productivity.

Spontaneous white mutants from sectors of Streptomyces hygroscopicus 111-81 were isolated. The comparison of morphological, cultural, and biochemical properties of the mutants and ancestor showed the differences in colors of aerial, substrate mycelia, and sporulation. Changes in resistance to antibiotics and sensitivity to lysozyme indicated alterations in cell walls and cell membranes of the mutants.

Biosurfactant production by antarctic facultative anaerobe Pantoea sp. during growth on hydrocarbons.

The facultative anaerobe Pantoea sp. strain A-13, isolated from ornithogenic soil of Dewart Island (Frazier Islands), Antarctica, produced glycolipid biosurfactants when grown on n-paraffins or kerosene as the sole source of carbon and energy. Hemolysis of erythrocytes, growth inhibition of Bacillus subtilis, and thin-layer chromatography studies have suggested that the secreted glycolipids are rhamnolipids.

Actinomycins with altered threonine units in the beta-peptidolactone.

Five new members of the actinomycin family, actinomycins G2-G6 (2-6), are produced by Streptomyces iakyrus strain DSM 41873. Their structures were established by spectroscopic methods. Unlike actinomycin D (1), the alpha-ring of the novel compounds contains the unusual amino acid 3-hydroxy-5-methylproline, while the beta-ring includes N-methylalanine and either a chlorinated or hydroxylated threonine moiety.

Effects of nutrients on the production of AK-111-81 macrolide antibiotic by Streptomyces hygroscopicus.

The influence of different carbon and nitrogen sources on the production of AK-111-81 nonpolyenic macrolide antibiotic by Streptomyces hygroscopicus 111-81 was studied. Substitution of glucose with lactose or glycerol significantly affected maximal antibiotic AK-111-81 productivity as the growth rate was close to that of the basal fermentation medium. Addition of ammonium succinate to the fermentation medium markedly increased the antibiotic productivity as the growth rate was low.

Potential for biodegradation of hydrocarbons by microorganisms isolated from Antarctic soils.

Seventeen pure aerobic microbial isolates were obtained from soil samples of three regions of Antarctica: Casey Station, Dewart Island and Terra Nova Bay. Most of them were gram positive coryneform bacteria. Isolates were tested for their ability to grow on mineral salt agar plates supplemented with one of the following model n-alkanes or aromatic hydrocarbons: hexane, heptane, paraffin, benzene, toluene, naphthalene and kerosene.

A new antibiotic, TH818, and its properties.

Antibiotic TH818 was isolated and purified from a culture broth of Streptomyces fulvoviolaceus 818 by extraction and reversed-phase liquid chromatography. The antibiotic TH818 possesses high molecular mass and unique structure, constructed from carbohydrates, amino acids and lipids. The hydrolysis experiments showed the presence of six fatty acids (hexadecanoic, hexadecenoic, octadecanoic, iso-nonadecanoic, docosanoic and pentacosanoic acids), four sugars (glucose, galactose, N -acetylglucosamine and N -acetylgalactosamine), and seven amino acids (threonine, alanine, glutamic acid, glycine, serine and two unidentified).

Physiological and antagonistic potential of actinomycetes from loquat rhizosphere.

The microflora of Eriobotrya japonica (loquat) was studied by the serial dilutions-spread plate method. A variety of bacteria, fungi and actinomycetes was detected. The genus Steptomyces dominated in the population (83%).

Fatty acid composition of Streptomyces hygroscopicus strains producing antibiotics.

The fatty acid composition from mycelia of Streptomyces hygroscopicus strains was studied. A significant proportion of C18:2 was found in cultures. High levels of C16:0, iso-C18:0 and C18:1 were also detected in all S.

[Interaction of actinomycetes in relation to an intensification of protease biosynthesis].

This work was aimed at studying the interactions during the growth of Actinomyces rimosus producing proteases and Actinomyces violocinereus which did not synthesize secreted proteolytic enzymes. The production of proteases in the association of the actinomycetes was shown to be stimulated by metabolic products released by A. violocinereus into the surrounding medium.