Bacteriophage translocation

The occurrence of phages in the human body, especially in the gastrointestinal tract, raises the question of their potential role in the physiology and pathology of this system. Especially important is the issue of whether phages can pass the intestinal wall and migrate to lymph, peripheral blood, and internal organs and, if so, the effects such a phenomenon could have (such passage by bacteria, known as bacterial translocation, has been shown to cause various disturbances in humans, from immune defects to sepsis). Available data from the literature support the assumption that phage translocation can take place and may have some immunomodulatory effects. In addition, phages of the gut may play a protective role by inhibiting local immune reactions to antigens derived from gut flora.     

Loop formation by the transgeneWAP:6xHishGH in transgenic rabbit fibroblasts, revealed by fluorescencein situ hybridization to nuclear halos

Using fluorescence in situ hybridization (FISH) to somatic nuclear halos from transgenic rabbits WAP:6xHishGH, we present evidence for stability of transgenesis at the chromatin level. FISH performed on fibroblasts from a homozygous individual showed 2 independent loops from both chromosomes of pair 7. On a heterozygous individual, FISH detected a single loop. According to the concept of chromatin loops and their influence on gene expression, this shows that the human growth hormone transgene, which was actively expressed in mammary gland under the influence of the tissue-specific promoter, was inactive in examined skin fibroblasts.     

Exogenous abscisic acid increases stability of polysomes in embryos of triticale caryopses during germination

Some posttranslational processes that occur in embryos of germinating triticale caryopses treated with different concentrations of abscisic acid (ABA) were examined. ABA increased the ratio of cytoskeleton-bound polysomes in the total population of polysomes and depressed the share of free and membrane-bound polysomes. Using exogenous RNase, stability of the total polysomal population as well as each polysomal fraction was investigated. The total extractable polysomes isolated from embryonic tissues of germinating triticale caryopses treated with ABA were more stable than the polysomes isolated from the control sample caryopses. The contribution of the polysomes that were not digested by RNase was increased by higher concentrations of ABA applied during germination. At high concentrations of ABA (50, 100 μM), the quantitative contribution of polysomes in the total ribosomal fraction was almost 100% of the amount of polysomes before digestion and the modifications observed consisted mainly of the shift of the so-called heavy polysomes towards light polysomes, containing a few ribosomes. Within each polysomal population, cytoskeleton-bound polysomes (CBP and CMBP) were the most stable, which may imply that the bonds between polysomes and these protein filaments, created in all eukaryotic cells increased their stability. It is assumed that mRNAs are stabilised or destabilised by interaction of proteins with their various sequences. A plant hormone may depress or elevate the quantities of these proteins, thus regulating the stability of different mRNAs. The results confirm the multi-faceted mechanism of ABA-induced response, where one of the constituents is the effect of ABA on the stability of mRNAs molecules. The co-ordinated regulation of mRNAs synthesis and their stability provide plants with improved adaptability.     

Enzymes in Bast Fibrous Plant Processing

The program COST Action 847 Textile Quality and Biotechnology (2000–2005) has given an excellent chance to review the possibilities of the research, aiming at development of the industrial application of enzymes for bast fibrous plant degumming and primary processing. The recent advancements in enzymatic processing of bast fibrous plants (flax, hemp, jute, ramie and alike plants) and related textiles are given. The performance of enzymes in degumming, modification of bast fibres, roving, yarn, related fabrics as well as enzymatic bonding of lignocellulosic composites is provided.     

Studies on the side-chain hydroxylation of ifosfamide and its bromo analogue

Deutero-substituted (alpha,alpha,alpha',alpha'-tetradeuterated) derivatives of ifosfamide (IF-d(4)) and its bromo analogue were synthesised. In vitro metabolic studies showed that microsomal hydroxylation of IF-d(4) is slower than for unlabelled compound, suggesting that kinetic isotope effect operates during those transformations. At the same time deutero-substituted derivatives are more active against L1210 leukaemia in mice than unlabelled compounds, suggesting a negative role of side-chain hydroxylation metabolic pathways in the anticancer activity of ifosfamide and its analogues.     

Obstetrical prevention of human cancers. Review article

Cancer appears in the new form of cell life as a direct consequence of self-organising pre-cancer cells (dissipathogenic systems), whose further existence is disabled by extreme impairment of their metabolism. Life itself is the highest value, since instead of necrosis or apoptosis, the cellular system in an unfavourable environment can change its genetic identity provided that the improvement in its own metabolism leads to increased chaos by higher dissipation of matter and energy in its environment. Prolongation of human life has resulted by a longer period of old age which is favourable for self-organisation of dissipative neoplastic cells. Modern medicine has explained the relation of the cervical cancer to preterm births and to inadequate use of oral contraceptives and/or replacement, instead of supplementary, neurohormonal therapy. Therefore, as early as in the period of pregnancy reproductive cells should be protected due to their prime importance in the intergenerational passage of life. Disturbance of systemic autoregulation causes development of dissipathogenic state of cells. A single zygote, whose environment is also important for the future development of the next two generations that are initiated with its formation, defines the unique identity of each person, whose life is determined by free will and neoplasms.     

Recovery of the pubic symphysis on primiparous young and multiparous senescent mice at postpartum

It has been observed that parturition has a significant effect on female skeletal architecture and that age alters musculoskeletal tissues and their functions. We therefore hypothesized that multiparity affects the recovery of the pubic symphysis in senescent mice at postpartum and the morphology of the interpubic tissues. The pubic symphysis of primiparous young, virgin senescent (VS) and multiparous senescent (MS) Swiss mice was examined by light microscopy, transmission electron microscopy, morphometric analysis and immunohistochemistry. The mouse pubic symphysis was remodeled during the first pregnancy: the cellular phenotype and morphology changed to ensure a structurally safe birth canal, followed by recovery of the interpubic articulation after birth. The morphology of the pubic symphysis in the VS group was maintained in a state similar to that observed in virgin young mice. In contrast, MS mice exhibited an interpubic ligament characterized by extended fibrocyte-like cells, an opened interpubic articulation gap, compacted and thin collagen fibrils and scarce galectin-3-positive cells. Thus, we found that the cellular and extracellular characteristics of the pubic symphysis were altered by multiparity in senescent mice. These particular tissue characteristics of the MS group might be associated with an impaired recovery process at postpartum. Thus, a better understanding of the alterations that occur in the birth canal, including the pubic symphysis, due to multiparity in reproductively aged mice may contribute to our comprehension of the biological mechanisms that modify the skeleton and pelvic ligaments and even play a role in the murine model of pelvic organ prolapse.     

Diversity in the Protein N-Glycosylation Pathways Within the Campylobacter Genus

The foodborne bacterial pathogen, Campylobacter jejuni, possesses an N-linked protein glycosylation (pgl) pathway involved in adding conserved heptasaccharides to asparagine-containing motifs of >60 proteins, and releasing the same glycan into its periplasm as free oligosaccharides. In this study, comparative genomics of all 30 fully sequenced Campylobacter taxa revealed conserved pgl gene clusters in all but one species. Structural, phylogenetic and immunological studies showed that the N-glycosylation systems can be divided into two major groups. Group I includes all thermotolerant taxa, capable of growth at the higher body temperatures of birds, and produce the C. jejuni-like glycans. Within group I, the niche-adapted C. lari subgroup contain the smallest genomes among the epsilonproteobacteria, and are unable to glucosylate their pgl pathway glycans potentially reminiscent of the glucosyltransferase regression observed in the O-glycosylation system of Neisseria species. The nonthermotolerant Campylobacters, which inhabit a variety of hosts and niches, comprise group II and produce an unexpected diversity of N-glycan structures varying in length and composition. This includes the human gut commensal, C. hominis, which produces at least four different N-glycan structures, akin to the surface carbohydrate diversity observed in the well-studied commensal, Bacteroides. Both group I and II glycans are immunogenic and cell surface exposed, making these structures attractive targets for vaccine design and diagnostics.In eukaryotes, glycosylated proteins are ubiquitous components of extracellular matrices and cellular surfaces. Their oligosaccharide moieties are implicated in a wide variety of essential cell-cell and cell-matrix processes ranging from immune recognition to cancer development. The first general protein glycosylation (pgl)¹ pathway was discovered in the epsilonproteobacterium Campylobacter jejuni (1). The organism transfers a conserved heptasaccharide en bloc to asparagine residues within the sequon D/E- X₁-N-X₂-S/T (X₁, X₂ ≠ P) of >60 glycoproteins (2–4). Furthermore, the pathway can be functionally transferred into Escherichia coli, and the oligosaccharyltransferase (OTase), PglB, is capable of adding foreign sugars to acceptor proteins (5–7). C. jejuni PglB also possesses hydrolase activity, influenced by the cellular growth phase and osmotic environment, releasing free oligosaccharides (fOS) into the periplasmic space in a 10:1 ratio relative to the amount of heptasaccharide N-linked to protein (8, 9).The C. jejuni N-linked heptasaccharide is conserved in structure in both C. jejuni and C. coli, the two most commonly isolated pathogenic Campylobacter species and major causes of human enteritis worldwide (10, 11). All campylobacters, but one, possess conserved pgl genes required for N-linked protein glycosylation ((12) and this study). This post-translational modification in C. jejuni influences DNA uptake, chicken and mouse colonization, epithelial cell adherence and invasion, recognition by human sera, and binding to the macrophage galactose lectin (MGL) receptor on dendritic cells (2, 13–17). Several Campylobacter species have now been recognized as emerging pathogens and causative agents of human gastroenteritis (e.g. C. upsaliensis and C. hyointestinalis), gingivitis, periodontitis, and human abortions (e.g. C. rectus, C. concisus, C. gracilis, C. showae, and C. upsaliensis) and inflammatory bowel disease in children (e.g. C. concisus) (18). Other species cause venereal disease and infertility in cattle (C. fetus subsp. venerealis; Cfv) or abortions in sheep (C. fetus subsp. fetus; Cff) (19).In this study, we used phylogenetic, immunological, structural and glycoproteomic studies to compare the N-glycosylation systems of 29 Campylobacter species and identified unexpected variations. Thus, although the pathway is a common feature within this genus, variability in the N-glycans and fOS at the species level suggests that each species possess a unique array of glycosyltransferases, which correlate with their phylogenetic relatedness.