171,557 research outputs found
Tumor Necrosis Factor-a Neutralizing Antibodies Induced by a Glycolaldehyde-Modified C- terminal Polypeptide.
No full textTNF-a is a pro-inflammatory cytokine that is overexpressed in diverse inflammatory states such as rheumatoid arthritis. Anti-TNF therapies, including monoclonal antibodies (Abs), have demonstrated remarkable success in management of arthritis and other chronic inflammatory diseases. The possibility to elicit autoAbs to TNF-a (beneficial autoimmunity) has been proposed as an immunotherapeutic approach to neutralize systemic TNF-a (1). Studies using a DNA vaccination strategy in rat adjuvant arthritis mapped several epitopes for natural anti-TNF-a autoAbs in the C-terminal portion of the sequence. We previously showed that aldehyde-tagged peptide conjugates representing immunogenic epitopes of toxic shock syndrome toxin–1, could induce anti-toxin neutralizing Abs without the need of potent adjuvants (2). In the present study, using a C-terminal TNF-a recombinant polypeptide, we followed a similar approach to generate neutralizing Abs against TNF-a in Lewis rats. Immunized rats showed less severe symptoms in the collagen induced arthritis ( CIA) model.
1. Dalum I. et. al. Therapeutic antibodies elicited by immunization against TNF-alpha. Nat Biotechnol 1999. 17:666-669.
2. Bavoso A, Ostuni A, De Vendel J, Pollaro F, Armentano F, Knight T, Makker S. and A. Tramontano. Aldehyde modification of peptide immunogen enhances protein-reactive antibody response to toxic shock syndrome toxin-1. J Pept Sci 2006. 12:843-849
The lncRNA HOTAIR links the repressor Snail to epigenetic modifications of specific genomic sites in Epithelial-to-Mesenchymal Transition
No full textThe lncRNA HOTAIR links the repressor Snail to epigenetic modifications of specific genomic sites in Epithelial-to-Mesenchymal Transition
Cecilia Battistelli 1,§, Carla Cicchini 1,§,, Laura Santangelo 1, Anna Tramontano 2, Marco Tripodi 1,3
1Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, Italy
2Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Physics, Sapienza University of Rome, Rome, Italy
3National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy.
§Co-first authors.
Co-corresponding authors
The transcription factor Snail is a master regulator of cellular identity and Epithelial-to-Mesenchymal Transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail specific binding sites is unclear. Here we report that the long non-coding (lnc)RNA HOTAIR mediates a physical interaction between Snail and EZH2, enzymatic subunit of the Polycomb Repressive Complex 2 (PRC2) and main writer of chromatin repressive marks. The Snail repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate a lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT
Sequenza peptidica isolata nel dominio II tipo immunoglobulina del recettore I del fattore di crescita dell'endotelio vascolare e legante l'integrina alpha5beta1 ad attivita' proangiogenica.
No full textNew predictions for single top production at hadron colliders
No full textWe present the next-to-leading order calculation for single-top production at hadron colliders. Our approach is novel in the fact that the calculation has been performed starting from the 2 → 3 Born process, qg → q'tb, keeping the
b-quark massive. A first comparison with the predictions based on the 2 → 2 Born process, using the b distribution function, is shown. Finally, we present, for the first time, the NLO prediction for the differential distributions of the spectator b both at the Tevatron and at the LHC
HIV-1 reverse transcriptase inhibition by a dipyridodiazepinone derivative: BI-RG-587
No full textThe dipyridodiazepinone derivative 6,11-dihydro-11-cyclopropyl-4-methyldipyrido[2,3-b:2',3'-e]-[1,4] diazepin-6-one (BI-RG-587) selectively inhibits human immunodeficiency virus type 1 (HIV-1) replication by suppressing HIV-1 reverse transcriptase activity. Both RNA- and DNA-dependent polymerase associated activities of this enzyme were found to be inhibited by BI-RG-587 in a pattern dependent on the template used. The lowest IC50 values were obtained using poly(rC)-oligo(dG)12-18 and poly(dA)-oligo(dT)12-18 as template-primer. For the RNA-dependent activity poly(rC)-oligo(dG)12-18 and dGTP appeared to enhance the inhibition of the RNA-dependent enzyme activity by BI-RG-587, with the effect of poly(rC)-oligo(dG)12-18 dominating that of dGTP. Poly(rA)-oligo(dT)10 seemed to decrease the inhibition whereas poly(rU)-oligo(dA)12-18 or poly(rG)-oligo-(dC)12-18 had no effect. dATP, dTTP and dCTP, three nucleotide triphosphates, also had no impact on the inhibition. Differences were observed for the template-dependent action of BI-RG-587 against the DNA-dependent enzyme activity. Both substrates were required to allow the inhibition by BI-RG-587 in the poly(dC)-oligo(dG)12-18 and dGTP reaction, whereas only the template and enzyme interaction seemed to be necessary for the poly(dA)-oligo(dT)12-18 and dTTP reaction. The different behaviors of DNA- and RNA-dependent DNA polymerase activities could indicate either the presence of different active sites for distinct activities or the presence of a unique active site with different configurations depending upon the template used. Also, BI-RG-587 showed a mutually exclusive inhibition when combined with two other classes of HIV-1 RT inhibitors represented by phosphonoformic acid and 3'-azido-3'-dideoxythymidine triphosphate
Thyrotropin and dibutyryl cyclic AMP increase levels of c-myc and c-fos mRNAs in cultured rat thyroid cells.
No full textWe have studied the effects of thyrotropin (TSH) on the growth and on the levels of the mRNAs of the cellular proto-oncogenes, c-myc, and c-fos, in the specific target of TSH action, the thyroid follicular cell. FRTL5 cells, a cloned line from normal rat thyroid gland that depends upon TSH for its replication, were maintained in a quiescent state for 5 days by keeping them in a medium devoid of serum or TSH. The addition of bovine TSH (bTSH, 1 nM) increased DNA synthesis and stimulated cell proliferation after a lag period of 24 h. This growth response was anteceded by prompt, but transient, increases in the levels of c-myc and c-fos mRNAs, with peak responses at 60 and 30 min, respectively. The minimally and maximally effective concentrations of bTSH were 0.01 mM and 1.0 nM, respectively. Dibutyryl cAMP (Bt2cAMP) stimulated cell growth and increased the level of c-myc mRNA in a concentration-dependent manner, with maximum effects at a Bt2cAMP concentration of 1 mM. At the single concentration tested (1 mM), Bt2cAMP also increased the level of c-fos mRNA. Hence, bTSH-stimulated mitogenesis in quiescent FRTL5 cells is associated with rapid, but short-lived, increases in the levels of the mRNAs of the proto-oncogenes, c-myc and c-fos. Since bTSH is known to stimulate adenylate cyclase in these cells, and since the effect of TSH on c-myc and c-fos mRNAs is mimicked by Bt2cAMP, it is possible that these responses to bTSH are mediated, at least in part, by cAMP
The role of molecular modelling in biomedical research
No full textThe synergy between experimental and computational biology has greatly benefited both fields, providing invaluable information in many different areas of the life sciences. This minireview will focus on one specific aspect of computational biology, molecular modelling, and describe a few examples highlighting the effectiveness of protein structural analysis and modelling in providing relevant information about systems of biomedical interest. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved
Abdominoplasty after bariatric surgery: Comparison of three different techniques
No full textBACKGROUND: Abdominoplasty after massive weight loss is not a cosmetic procedure. The aim of this study was to compare three different techniques for postbariatric abdominoplasty. METHODS: All postbariatric patients that have undergone abdominoplasty from January 2013 to December 2016 were included in the study. Patients were divided into 3 groups: Subjects who underwent standard procedure were allocated ingroup A; those cases performed using a synthetic glue were assigned to group B; cases performed with an energy device were inserted in group C. Operative time, length of stay and complications were recorded. RESULTS: Seventy-one abdominoplasties were performed in the selected period. Mean operative time was shorter (P<0.01) in group C (94.3±2.7 minutes) than in group A(112.1±16.8 minutes) and in group B (121±13.2 minutes). Mean length of stay was significantly reduced (P<0.01) in group C (2.4±0.7) when compared to group A (3.5±0.6 days) and group B (3.1±0.5 days). Bleeding occurred in 21 (29.5%) patients (15 in group A, 4 in groupB, 3 in group C; P<0.01). Seroma was detected in 22(30.9%) subjects (14 in group A, 2in group B, 6 in group C; P<0.01). Wound dehiscence and umbilical necrosis were recorded in 7 (9.9%) and 9 (12.6%) patients respectively, without statistical differences. CONCLUSIONS: Both synthetic glue and energy device improve outcomes of postbariatric abdominoplasties. The glue reduces rates of bleeding and seroma. The energy deviceimproves intraoperative hemostasis and shortens operative time. copy
The exploding field of the HCV polymerase non-nucleoside inhibitors: summary of a first generation compounds
No full textThe hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) is strictly essential for viral replication
and it has been used as viral target for anti-HCV drug development. All small molecules which have been identified to be
selective non-nucleoside inhibitors (NNI) of the HCV RdRp to date are reported
Biochemical characterization of the HIV-1 integrase 3’-processing activity and its inhibition by phosphorotioate oligonucleotides
No full textTo better understand HIV-1 integrase (IN) functions, we determined the kinetic parameters of the 3'-processing reaction. Steady-state kinetic analysis performed using Dixon plots indicated that the concentration of active enzyme was 10-fold lower than that calculated by protein determination. The turnover number was low, suggesting that IN remained bound to DNA after cleavage. The catalytic efficiency increased 10-fold from 30 to 37 degrees C and 2-fold from 37 to 42 degrees C. In enzyme assays carried out at 37 degrees C, both single-and double-stranded phosphorothioate oligos bound to IN with an efficiency comparable to that of the phosphodiester duplex substrate. The competition efficiency of single-stranded oligos was directly related to the sequence length. On the other hand, phosphorothioate duplex U5 LTRs modified in the plus strand were capable of both competing with the substrate and directly inhibiting the 3'-processing activity. These results suggest that, in addition to other modes of action (inhibition of gp120-CD4 interaction and reverse transcriptase), phosphorothioate hetero- and homopolimeric oligos also potently inhibit the IN activity
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