Regulatory role of cathepsin D in apoptosis

Cathepsin D (CTSD, EC 3.4.23.5) is well known aspartyl protease. Among different role in cell physiology, a new function of this enzyme is examined. Cathepsin D is an important regulator of apoptotic pathways in cells. It acts at different stage of intrinsic and extrinsic pathway of apoptosis. Cathepsin D can either induce apoptosis in presence of cytotoxic factors, but in certain studies an inhibitory role in apoptosis was also reviewed. Detailed review of involvement of cathepsin D in cell apoptosis is a purpose of this paper.     

Human gliosarcoma-associated ganglioside composition is complex and distinctive as evidenced by high-performance mass spectrometric determination and structural characterization

Gangliosides (GGs), involved in malignant alteration and tumor progression/invasiveness, are considered as tumor biomarkers or therapeutic targets. Here, we describe the first systematic GG composition characterization in human gliosarcoma versus normal brain tissue using our recently developed mass spectrometry (MS) methods, based on nano-electrospray (nano-ESI), Fourier-transform ion cyclotron resonance (FT-ICR), and chip nano-ESI quadrupole time-of-flight (QTOF), complemented by thin-layer chromatographic (TLC) analysis and quantification. Combined MS enabled detection and structural assignment of 73 distinct GG species: many more than reported so far for investigated gliomas. Apart from the 7.4-times lower total GG content, gliosarcoma contained all major brain-associated species, however, in very altered proportions, exhibiting a highly distinctive pattern: GD3 (48.9%)>GD1a/nLD1>GD2/GT3>GM3>GT1b>GM2>GM1a/GM1b/nLM1>LM1>GD1b>GQ1b. MS also revealed abundant O-Ac-GD3; its sequencing provided structural evidence to postulate a novel O-Ac-GD3 isomer O-acetylated at the inner Neu5Ac-residue, previously not structurally confirmed. The high sensitivity and mass accuracy permitted the assignment of unusual minor species: GM4, Hex-HexNAc-nLM1, Gal-GD1, Fuc-GT1, GalNAc-GT1, O-Ac-GM3, di- O-Ac-GD3O-Ac-GD3, and O-Ac-GT3, not previously reported as glioma-associated. The gliosarcoma-expressed GA2 might represent a marker distinguishing astrocytic from oligodendroglial tumors. This is, to our knowledge, so far the most complete GG composition characterization of certain glioma, which demonstrates that our MS-based approach could provide essential structural information relevant to glycosphingolipid role(s) in brain tumor biology, differential diagnosis/prognosis and novel treatment concepts.     

Evidence for recent horizontal transfer of gypsy-homologous LTR-retrotransposon gtwin into Drosophila erecta followed by its amplification with multiple aberrations

Long terminal repeat (LTR) retrotransposon gtwin was initially discovered in silico, and then it was isolated as gypsy-homologous sequence from Drosophila melanogaster strain, G32. The presence of ORF3 suggests, that gtwin, like gypsy, may be an endogenous retrovirus, which can leave the cell and infect another one. Therefore, in this study we decided to investigate the distribution of gtwin in different species of the melanogaster subgroup in order to find out whether gtwin can be transferred horizontally as well as vertically. Gtwin was found in all 9 species of this subgroup, hence it seems to have inhabited the host genomes for a long time. In addition, we have shown that in the Drosophila erecta genome two gtwin families are present. The first one has 93% of identity to D. melanogaster element and is likely to be a descendant of gtwin that existed in Drosophila before the divergence of the melanogaster subgroup species. The other one has >99% of identity to D. melanogaster gtwin. The most reasonable explanation is that this element has been recently horizontally transferred between D. melanogaster and D. erecta. The number and variety of gtwin copies from the "infectious" family suggest that after the horizontal transfer into D. erecta genome, gtwin underwent amplification and aberrations, leading to the rise of its diverse variants.     

Loss of MT1‐MMP causes cell senescence and nuclear defects which can be reversed by retinoic acid

MT1-MMP (MMP14) is a collagenolytic enzyme located at the cell surface and implicated in extracellular matrix (ECM) remodeling. Mmp14^−/− mice present dwarfism, bone abnormalities, and premature death. We demonstrate herein that the loss of MT1-MMP also causes cardiac defects and severe metabolic changes, and alters the cytoskeleton and the nuclear lamina structure. Moreover, the absence of MT1-MMP induces a senescent phenotype characterized by up-regulation of p16^INK4a and p21^CIP1/WAF1, increased activity of senescence-associated β-galactosidase, generation of a senescence-associated secretory phenotype, and somatotroph axis alterations. Consistent with the role of retinoic acid signaling in nuclear lamina stabilization, treatment of Mmp14^−/− mice with all-trans retinoic acid reversed the nuclear lamina alterations, partially rescued the cell senescence phenotypes, ameliorated the pathological defects in bone, skin, and heart, and extended their life span. These results demonstrate that nuclear architecture and cell senescence can be modulated by a membrane protease, in a process involving the ECM as a key regulator of nuclear stiffness under cell stress conditions.     

Jasmonic acid perception by COI1 involves inositol polyphosphates in Arabidopsis thaliana

Plant responses to wounding are part of their defense responses against insects, and are tightly regulated. The isoleucin conjugate of jasmonic acid (JA‐Ile) is a major regulatory molecule. We have previously shown that inositol polyphosphate signals are required for defense responses in Arabidopsis; however, the way in which inositol polyphosphates contribute to plant responses to wounding has so far remained unclear. Arabidopsis F‐box proteins involved in the perception of JA‐Ile (COI1) and auxin (TIR1) are structurally similar. Because TIR1 has recently been shown to contain inositol hexakisphosphate (InsP₆) as a co‐factor of unknown function, here we explored the possibility that InsP₆ or another inositol polyphosphate is required for COI1 function. In support of this hypothesis, COI1 variants with changes in putative inositol polyphosphate coordinating residues exhibited a reduced interaction with the COI1 target, JAZ9, in yeast two‐hybrid tests. The equivalent COI1 variants displayed a reduced capability to rescue jasmonate‐mediated root growth inhibition or silique development in Arabidopsis coi1 mutants. Yeast two‐hybrid tests using wild‐type COI1 in an ipk1Δ yeast strain exhibiting increased levels of inositol pentakisphosphate (InsP₅) and reduced levels of InsP₆ indicate an enhanced COI1/JAZ9 interaction. Consistent with these findings, Arabidopsis ipk1‐1 mutants, also with increased InsP₅ and reduced InsP₆ levels, showed increased defensive capabilities via COI1‐mediated processes, including wound‐induced gene expression, defense against caterpillars or root growth inhibition by jasmonate. The combined data from experiments using mutated COI1 variants, as well as yeast and Arabidopsis backgrounds altered in inositol polyphosphate metabolism, indicate that an inositol polyphosphate, and probably InsP₅, contributes to COI1 function.     

In vitro assay of the antimicrobial activity of kephir against bacterial and fungal strains

Kephir is a fermented carbonated refreshing milk, with a slightly acidic aromatic taste and creamy foam composition which contains lactobacilli, leuconostocci, acetic acid bacteria, lactostreptococci and yeasts. Recent studies have demonstrated its antibacterial, immunostimulating, antitumoral and cholesterol-lowering activities.

Purpose

The purpose of this study was to investigate the antimicrobial activity of kephir against Bacillus subtilis spp. spizizenii ATCC 6633, Staphylococcus aureus ATCC 6538, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 8739, Salmonella enteritidis ATCC 13076, Pseudomonas aeruginosa ATCC 9027 and Candida albicans ATCC 10231. The kephir fermented for 24 h and 48 h, as well and after 7 days preservation at 4–8 °C was tested by in vitro disk diffusion method. The intensity of the antimicrobial activity was interpreted by comparison with two antibiotics, i.e. ampicillin and neomycin.

Results

The antimicrobial activity of 24 h as well as 48 fermented kephir, fresh or after 7 days preservation at 4–8 °C was similar and observed against B. subtilis, S. aureus, E. coli, E. faecalis and S. enteritidis. For E. coli, E. faecalis and S. enteritidis the antimicrobial activity was superior to both tested antibiotics and for B. subtilis and S. aureus to one antibiotic. The tested products exhibited no activity against P. aeruginosa and C. albicans.

Conclusion

Kephir is exhibiting large spectrum and strong antibacterial activity probably due to the complex viable probiotic strains association producing antimicrobial substances.     

Complete genome sequence of Oceanithermus profundus type strain (506)

Oceanithermus profundus Miroshnichenko et al. 2003 is the type species of the genus Oceanithermus, which belongs to the family Thermaceae. The genus currently comprises two species whose members are thermophilic and are able to reduce sulfur compounds and nitrite. The organism is adapted to the salinity of sea water, is able to utilize a broad range of carbohydrates, some proteinaceous substrates, organic acids and alcohols. This is the first completed genome sequence of a member of the genus Oceanithermus and the fourth sequence from the family Thermaceae. The 2,439,291 bp long genome with its 2,391 protein-coding and 54 RNA genes consists of one chromosome and a 135,351 bp long plasmid, and is a part of the Genomic Encyclopedia of Bacteria and Archaea project.