Economic and environmental aspects of cellulose-based bioethanol production in Hungary

First generation bioethanol production and its use as fuel were characterized by a significant take- off in the mid-2000s. The fast growth was followed by a very sharp slowdown in line with the changed position of the European Union. The change of direction aims that priority should be given to the polysaccharide-based materials from the potential raw materials of bioethanol production, which are available not from crops, but in the form of agricultural and forestry waste and by-products. The role, economic and environmental aspects of bioethanol as the fuel of the future arise open issues. With our examinations we want to contribute to respond to those questions which analyse the impacts and economy of the bioethanol production based on agricultural by-products. In this framework we compared the quantity of cellulose can be obtained from potential raw materials, we made economic calculations, and we analysed the impacts of raw material acquisition on landscape ecology. Our aim in all of this was to map the advantages and disadvantages of the second generation bioethanol production

Rheumatoid arthritis and smoking: putting the pieces together

Besides atherosclerosis and lung cancer, smoking is considered to play a major role in the pathogenesis of autoimmune diseases. It has long been known that there is a connection between rheumatoid factor-positive rheumatoid arthritis and cigarette smoking. Recently, an important gene–environment interaction has been revealed; that is, carrying specific HLA-DRB1 alleles encoding the shared epitope and smoking establish a significant risk for anti-citrullinated protein antibody-positive rheumatoid arthritis. We summarize how smoking-related alteration of the cytokine balance, the increased risk of infections (the possibility of cross-reactivity) and modifications of autoantigens by citrullination may contribute to the development of rheumatoid arthritis

Gliko-immunológiai vizsgálatok autoimmun folyamatok kialakulásának felderítésére = Glycoimmunological studies in search of the mechanism of autoimmune processes

Munkánk során az autoimmunitás glikoimmunológiai vonatkozásait vizsgáltuk. Igazoltuk, hogy glükózaminoglikánnal reagáló természetes autoantitestek igen nagy mennyiségben vannak jelen a normál felnőtt szérumban, és szintjük rheumatoid arthritisben szignifikánsan emelkedett. A kondroitin szulfát C ellenes IgM természetes autoantitestet mint a rheumatoid arthritis új stádium markerét azonosítottuk. Igazoltuk, hogy az ízületekre jellemző legjelentősebb glikozidáz enzim a hexózaminidáz, melynek fő forrása a synoviális fibroblaszt mind rheumatoid arthritisben, mint osteoarthritisben. Ugyanezen sejtek csak igen kis mértékben járulnak hozzá az ízületekben a béta glükuronidáz termeléshez. A Toll like receptor ligand oligoszacharid oldalláncokat létrehozni képes endoglikozidáz enzimek ízületen belüli expressziója rendkívül alacsony, míg az ismeretlen funkciójú Hc gp 39 (CHI3L1) kiemelkedően magas ízületi expressziót mutat. Adatbázis elemzéssel kimutattuk, a kísérletesen igazolt T sejtek epitópok glikozilációja rendkívül alacsony a normál fehérjékéhez képest, az autoantigén jelleg összefügg a molekula N-glikozilációjával, valamint, hogy a bakteriális-humán megegyező szekvenciák N glikozilációja meglepően alacsony. Összefüggést mutattunk ki a glükuronidázt kódoló KLOTHO gén egy SNP-je, a lizoszomális GusB gén két SNP-jének együttes előfordulása, valamint a rheumatoid arthritis között. | In our work we investigated glycoimmunological aspects of autoimmunity. We have shown that natural autoantibodies reactive with glycosaminoglycans are present in large amounts in healthy adult serum, and the level is significantly elevated in rheumatoid arthritis. We identified the chondroitin sulphate C-specific IgM antibody as a novel disease stage marker in rheumatoid arthritis. We found that the major glycosidase enzyme in the joint is hexosaminidase, the primary source of which are synovial fibroblasts both in rheumatoid arthritis and osteoarthritis. The same cells are characterized by very small contribution to the beta-glucuronidase production of the joints. Endoglycosidases that generate TLR ligand oligosaccharides show very low expression within the joints. On the contrary, Hc gp 39 (CHIL3L1), a member of the chitinase family of proteins with unknown function shows a robust expression within the joints. Using database analysis we have found association between the autoantigenic nature of a given protein with its N-glycosylation, surprisingly low N-glycosylation of experimentally proven T cell epitopes as well as strikingly low expression of sequences shared by bacteria and human proteins. We found significant association of an SNP of the KLOTHO gene, the simultaneous presence of two GusB SNPs and rheumatoid arthritis

Differential impact of exportin-1-mediated nuclear export of RNAs on the RNA content of extracellular vesicle subpopulations

Extracellular vesicles (EVs) are membrane-enclosed subcellular structures released by all cell types. EVs have important roles in both cellular homeostasis and intercellular communication. Recent progress in the field revealed substantial heterogeneity of EVs even within the size-based EV categories. Here we addressed the question whether the exportin-1 (XPO1)-mediated nuclear export of RNAs contributed to the EV heterogeneity. Size-based populations were separated from the conditioned media of three cell lines (U937, THP-1 and 5/4E8) in steady-state condition. The effects of activation and leptomycin B treatment (to inhibit the XPO1-mediated nuclear export of RNAs) were also tested in the case of the two monocytic cell lines. Agilent Pico and Small chips were used to characterize RNAs, fragment analysis was performed, and EV-associated miRNAs were tested by Taqman assays. As expected, we found the highest small RNA/total RNA ratio and the lowest rRNA/ total RNA proportion in small EVs (~ 50–150 nm). Profiles of the small RNAs within different size-based EV categories significantly differed based on the activation status of the EV releasing cells. Leptomycin B had a differential inhibition on the tested small RNAs in EVs, even within the same EV size category. A similar heterogeneity of the EV miRNA content was observed upon cellular activation and nuclear export inhibition. Here we complement the already existing knowledge on EV heterogeneity by providing evidence that the RNA cargo varies depending on the EV size-based category, the releasing cell type, the functional status of the releasing cells and the exportin-1-mediated nuclear export of RNAs

The emerging and diverse roles of Src-like adaptor proteins in health and disease

Although Src-like adaptor proteins (SLAP-1 and SLAP-2) were mainly studied in lymphocytes, where they act as negative regulators and provide fine control of receptor signaling, recently, several other functions of these proteins were discovered. In addition to the well-characterized immunoregulatory functions, SLAP proteins appear to have an essential role in the pathogenesis of type I hypersensitivity, osteoporosis, and numerous malignant diseases. Both adaptor proteins are expressed in a wide variety of tissues, where they have mostly inhibitory effects on multiple intracellular signaling pathways. In this review, we summarize the diverse effects of SLAP proteins

Central role of nitric oxide in the pathogenesis of rheumatoid arthritis and sysemic lupus erythematosus

Nitric oxide (NO) has been shown to regulate T cell functions under physiological conditions, but overproduction of NO may contribute to T lymphocyte dysfunction. NO-dependent tissue injury has been implicated in a variety of rheumatic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Several studies reported increased endogenous NO synthesis in both SLE and RA, and recent evidence suggests that NO contributes to T cell dysfunction in both autoimmune diseases. The depletion of intracellular glutathione may be a key factor predisposing patients with SLE to mitochondrial dysfunction, characterized by mitochondrial hyperpolarization, ATP depletion and predisposition to death by necrosis. Thus, changes in glutathione metabolism may influence the effect of increased NO production in the pathogenesis of autoimmunity

Az allergia és az allergiás asztma pathomechanizmusának molekuláris biológiai és genetikai vizsgálata = Molecular biologic and genetic investigation of the pathomechanism of allergy and allergic asthma

Az asztmásokban szignifikánsan alacsonyabb volt az MCP-1 szint, mint az egészségesekben. Az asztmás csoporton belül az atópiásokban (IgE>100kU/l) szignifikánsan alacsonyabb volt az MCP-1 szint, mint a nem-atópiásokban. Az asztmások között szignifikánsan több olyan gyermeket találtunk, akik hordoztak legalább egy MBL mutációt és pozitívak voltak Chlamydophila pneumoniae (CP) ellenes IgG-re, mint a kontroll csoportban. Az asztmás csoporton belül szignifikánsan több allergiás-asztmás beteg volt pozitív CP-specifikus IgA-ra és IgA+IgG-re, mint nem-allergiás asztmás. A TNF? -308A allélja jelentősen megnöveli annak az esélyét, hogy a CP fertőzött gyermekekben asztma alakuljon ki. Az asztmás gyerekek között szignifikánsan magasabb volt a krónikus Mycoplasma pneumoniae (MP) fertőzöttek aránya (31.1% az asztmás gyermekekben és 18.1% az egészséges kontrollokban). A CCR5?32 allélfrekvenciája szignifikánsan magasabb volt a krónikus MP fertőzöttek között, mint a nem fertőzöttekben, illetve nem-krónikus fertőzöttekben. Ezzel szemben a krónikusan fertőzött asztmásokban alacsonyabb volt a CCR5?32 allélfrekvenciája, mint a krónikusan fertőzött kontrollokban. Az asztma biobankunkban 425 beteg DNS-ét és adatait gyűjtöttük össze. Emellett, 404 allergiás, de nem asztmás, illetve több mint 500 egészséges kontroll DNS-e, illetve adatai állnak rendelkezésünkre. Elkezdtük az asztma parciális genomszűrését a 11q13 genomrégióban 67 SNP genotipizálásával. | The serum levels of the MCP-1 protein were significantly lower in asthmatic children than in healthy controls. Furthermore, within the asthmatic group, the serum levels of MCP-1 were significantly lower in children with atopic phenotypes than with nonatopic phenotypes. Among asthmatic children carrying variant MBL alleles there were significantly more patients positive for C pneumoniae (CP)-specific IgG, than among control children with variant MBL genotypes. Significantly more allergic asthmatic patients were positive for (CP)-specific IgA and IgA+IgG than nonallergic asthmatic patients. Among asthmatic children carrying the TNF? -308A allele, there were significantly more patients positive for (CP)-specific IgG, than among control children carrying the same allele. In the asthmatic group significantly more children were positive for Mycoplasma pneumoniae (MP) -specific antibodies, than in the control group (31.1% vs. 18.1%). The allelic frequency of the CCR5?32 was significantly higher among MP-seropositive and than among MP-seronegative children. Significantly less MP-seropositive asthmatic than MP-seropositive control carries the CCR5?32 allele. We collected genomic DNA and clinical data from 425 children with asthma, 304 allergic, but without asthma and more than 500 healthy controls. We started the partial genome screening of asthma with genotyping 67 SNPs in chromosome 11q13

Isolation of Exosomes from Blood Plasma: Qualitative and Quantitative Comparison of Ultracentrifugation and Size Exclusion Chromatography Methods

BACKGROUND: Exosomes are emerging targets for biomedical research. However, suitable methods for the isolation of blood plasma-derived exosomes without impurities have not yet been described. AIM: Therefore, we investigated the efficiency and purity of exosomes isolated with potentially suitable methods; differential ultracentrifugation (UC) and size exclusion chromatography (SEC). METHODS AND RESULTS: Exosomes were isolated from rat and human blood plasma by various UC and SEC conditions. Efficiency was investigated at serial UC of the supernatant, while in case of SEC by comparing the content of exosomal markers of various fractions. Purity was assessed based on the presence of albumin. We found that the diameter of the majority of isolated particles fell into the size range of exosomes, however, albumin was also present in the preparations, when 1h UC at 4 degrees C was applied. Furthermore, with this method only a minor fraction of total exosomes could be isolated from blood as deduced from the constant amount of exosomal markers CD63 and TSG101 detected after serial UC of rat blood plasma samples. By using UC for longer time or with shorter sedimentation distance at 4 degrees C, or UC performed at 37 degrees C, exosomal yield increased, but albumin impurity was still observed in the isolates, as assessed by transmission electron microscopy, dynamic light scattering and immunoblotting against CD63, TSG101 and albumin. Efficiency and purity were not different in case of using further diluted samples. By using SEC with different columns, we have found that although a minor fraction of exosomes can be isolated without significant albumin content on Sepharose CL-4B or Sephacryl S-400 columns, but not on Sepharose 2B columns, the majority of exosomes co-eluted with albumin. CONCLUSION: Here we show that it is feasible to isolate exosomes from blood plasma by SEC without significant albumin contamination albeit with low vesicle yield