Cytokine structural taxonomy and mechanisms of receptor engagement

Seven discrete families of cytokines have been identified by sequence and structural analysis. Within this diverse set of protein folds, the hematopoietic growth factors and tumor necrosis factor-like cytokines display a remarkable degree of variation upon their respective topological frameworks. In addition, prototype X-ray structures of ligand-receptor complexes reveal two different strategies of receptor engagement

Sistema web para el proceso de ventas en Neoestructura Sac

Como parte de este estudio tenemos el desarrollo y la implementación del SistemaWeb para el proceso de ventas en Neoestructura SAC., empresa perteneciente al rubro de construcciones metálicas. Como objetivo principal se debe visualizar la influencia del Sistema en el proceso de ventas, cuyos resultados fueron satisfactorios tanto en el indicador Eficacia de cierre de ventas y grado de interés (hubo un aumento de la media una vez que se implemento el SistemaWeb en la empresa). Con el Sistema implementado en la empresa se demostró que hubo mayor rapidez en la manipulación de los documentos, el problema estaba poco a poco teniendo menos impacto; y con el SistemaWeb se logro que las demás áreas también mejoren sus procesos. Aplicamos la metodología SCRUM en el desarrollo del Sistema. Sistema web desarrollado con la arquitectura de Software MVC (Modelo-VistaControlador), código PHP y HTML.

In silico characterization of the family of PARP-like poly(ADP-ribosyl)transferases (pARTs)

BACKGROUND: ADP-ribosylation is an enzyme-catalyzed posttranslational protein modification in which mono(ADP-ribosyl)transferases (mARTs) and poly(ADP-ribosyl)transferases (pARTs) transfer the ADP-ribose moiety from NAD onto specific amino acid side chains and/or ADP-ribose units on target proteins. RESULTS: Using a combination of database search tools we identified the genes encoding recognizable pART domains in the public genome databases. In humans, the pART family encompasses 17 members. For 16 of these genes, an orthologue exists also in the mouse, rat, and pufferfish. Based on the degree of amino acid sequence similarity in the catalytic domain, conserved intron positions, and fused protein domains, pARTs can be divided into five major subgroups. All six members of groups 1 and 2 contain the H-Y-E trias of amino acid residues found also in the active sites of Diphtheria toxin and Pseudomonas exotoxin A, while the eleven members of groups 3 – 5 carry variations of this motif. The pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains. Some of these domain associations appear to be very ancient since they are observed also in insects, fungi, amoebae, and plants. The recently completed genome of the pufferfish T. nigroviridis contains recognizable orthologues for all pARTs except for pART7. The nearly completed albeit still fragmentary chicken genome contains recognizable orthologues for twelve pARTs. Simpler eucaryotes generally contain fewer pARTs: two in the fly D. melanogaster, three each in the mosquito A. gambiae, the nematode C. elegans, and the ascomycete microfungus G. zeae, six in the amoeba E. histolytica, nine in the slime mold D. discoideum, and ten in the cress plant A. thaliana. GenBank contains two pART homologues from the large double stranded DNA viruses Chilo iridescent virus and Bacteriophage Aeh1 and only a single entry (from V. cholerae) showing recognizable homology to the pART-like catalytic domains of Diphtheria toxin and Pseudomonas exotoxin A. CONCLUSION: The pART family, which encompasses 17 members in the human and 16 members in the mouse, can be divided into five subgroups on the basis of sequence similarity, phylogeny, conserved intron positions, and patterns of genetically fused protein domains

Breves Reflexiones Constitucionales Sobre Temas de Actualidad. Entrevista a Gerardo Eto Cruz

En la presente entrevista, el Dr. Eto plantea su opinión acerca de diversos temas de actualidad, en lo cuales se ve involucrado el Derecho Constitucional. Así pues, la línea de la presente entrevista recorre diversos temas como la legitimidad de la Constitución de 1993, sus avances, retrocesos y retos pendientes. Asimismo, realiza breves comentarios sobre las garantías constitucionales incidiendo sobretodo en la acción de amparo; luego analiza temas diversos como la tenencia de armas, la ley de la promoción de la alimentación saludable (la mal llamada ley de la comida chatarra), así como el derecho sucesorio de las uniones de hecho

Short-Term effect of COX-2 selective inhibitor as an adjunct for the treatment of periodontal disease: a clinical double-blind study in humans

Adjunctive therapeutic strategies that modulate the inflammatory mediators can play a significant role in periodontal therapy. In this double-blind, placebo-controlled study, 60 subjects diagnosed as periodontitis patients were evaluated for 28 days after periodontal treatment combined with selective cyclooxygenase-2 (COX-2) inhibitor. The experimental group received scaling and root planning (SRP) combined with the Loxoprofen antiinflammatory drug (SRP+Loxoprofen). The control group received SRP combined with placebo (SRP+placebo). Plaque index (PI), probing pocket depth (PD) and bleeding on probing (BOP) were monitored with an electronic probe at baseline and after 14 and 28 days. Both groups displayed clinical improvement in PD, PI and BOP. They also showed statistically similar values (p>0.05) of PD reduction on day 14 (0.4 mm) and on day 28 (0.6 mm). At the baseline, few deeper sites (>7 mm) from SRP+Loxoprofen group were responsible and most PD reduction was observed after 14 days (p<0.05). The percentage of remaining deep pockets (>7 mm) after 14 days in the SRP+Loxoprofen group was significantly lower (p<0.05) than in the SRP+placebo group. Loxoprofen presents potential effect as an adjunct of periodontal disease treatment, but long-term clinical trials are necessary to confirm its efficacy.Estratégias terapêuticas adjuvantes que modulam os mediadores inflamatórios podem ter função significante na terapia periodontal. Neste estudo duplo-cego controlado com placebo, 60 indivíduos diagnosticados com periodontite foram avaliados por 28 dias após tratamento periodontal combinado com inibidor seletivo de COX-2. O grupo experimental foi tratado com raspagem e alisamento radicular combinado com medicação anti-inflamatória Loxoprofeno (RAR+Loxoprofen). O grupo controle foi tratado com raspagem e alisamento radicular combinado com medicação placebo (Raspagem e alisamento radicular - RAR+placebo). Presença de placa (PI), profundidade de sondagem (PS) e sangramento à sondagem (SS) foram monitoradas com auxílio de uma sonda computadorizada no início do estudo e após 14 e 28 dias. Os dois grupos demonstraram melhora clínica em relação a PS, PI e SS. Também foi observado valores semelhantes (p>0,05) de redução da PS nos períodos de 14 dias (0,4 mm) e 28 dias (0,6 mm). No início do estudo, alguns sítios profundos (>7 mm) do grupo RAR+Loxoprofen foram os responsáveis pela maior redução da PS depois de 14 dias (p<0,05). A porcentagem de bolsas periodontais profundas >7 mm após 14 dias no grupo RAR+Loxoprofen foi significativamente inferior do que o grupo RAR+placebo (p<0.05). A medicação Loxoprofen apresenta potencial efeito adjuvante à terapia periodontal, mas estudos de longo prazo são necessários para confirmar sua eficácia.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)FAPESPSankyo Pharma Ltda

Expression of osteoblastic phenotype in periodontal ligament fibroblasts cultured in three-dimensional collagen gel

Objective : To investigate the influence of a three-dimensional cell culture model on the expression of osteoblastic phenotype in human periodontal ligament fibroblast (hPDLF) cultures. Material and Methods : hPDLF were seeded on bi-dimensional (2D) and three-dimensional (3D) collagen type I (experimental groups) and and on a plastic coverslip (control) for up to 14 days. Cell viability and alkaline phosphatase (ALP) activity were performed. Also, cell morphology and immunolabeling for alkaline phosphatase (ALP) and osteopontin (OPN) were assessed by epifluorescence and confocal microscopy. The expression of osteogenic markers, including alkaline phosphatase, osteopontin, osteocalcin (OC), collagen I (COL I) and runt-related transcription factor 2 (RUNX2), were analyzed using real-time polymerase chain reaction (RT-PCR). Mineralized bone-like nodule formation was visualized by microscopy and calcium content was assessed quantitatively by alizarin red assay. Results : Experimental cultures produced an increase in cell proliferation. Immunolabeling for OPN and ALP in hPDLF were increased and ALP activity was inhibited by three-dimensional conditions. OPN and RUNX2 gene expression was significantly higher on 3D culture when compared with control surface. Moreover, ALP and COL I gene expression were significantly higher in three-dimensional collagen than in 2D cultures at 7 days. However, at 14 days, 3D cultures exhibited ALP and COL I gene expression significantly lower than the control, and the COL I gene expression was also significantly lower in 3D than in 2D cultures. Significant calcium mineralization was detected and quantified by alizarin red assay, and calcified nodule formation was not affected by tridimensionality. Conclusion : This study suggests that the 3D cultures are able to support hPDLF proliferation and favor the differentiation and mineralized matrix formation, which may be a potential periodontal regenerative therapy

Novel C16orf57 mutations in patients with Poikiloderma with Neutropenia: bioinformatic analysis of the protein and predicted effects of all reported mutations

<p>Abstract</p> <p>Background</p> <p>Poikiloderma with Neutropenia (PN) is a rare autosomal recessive genodermatosis caused by <it>C16orf57 </it>mutations. To date 17 mutations have been identified in 31 PN patients.</p> <p>Results</p> <p>We characterize six PN patients expanding the clinical phenotype of the syndrome and the mutational repertoire of the gene. We detect the two novel <it>C16orf57 </it>mutations, c.232C>T and c.265+2T>G, as well as the already reported c.179delC, c.531delA and c.693+1G>T mutations. cDNA analysis evidences the presence of aberrant transcripts, and bioinformatic prediction of C16orf57 protein structure gauges the mutations effects on the folded protein chain.</p> <p>Computational analysis of the C16orf57 protein shows two conserved H-X-S/T-X tetrapeptide motifs marking the active site of a two-fold pseudosymmetric structure recalling the 2H phosphoesterase superfamily. Based on this model C16orf57 is likely a 2H-active site enzyme functioning in RNA processing, as a presumptive RNA ligase.</p> <p>According to bioinformatic prediction, all known <it>C16orf57 </it>mutations, including the novel mutations herein described, impair the protein structure by either removing one or both tetrapeptide motifs or by destroying the symmetry of the native folding.</p> <p>Finally, we analyse the geographical distribution of the recurrent mutations that depicts clusters featuring a founder effect.</p> <p>Conclusions</p> <p>In cohorts of patients clinically affected by genodermatoses with overlapping symptoms, the molecular screening of <it>C16orf57 </it>gene seems the proper way to address the correct diagnosis of PN, enabling the syndrome-specific oncosurveillance.</p> <p>The bioinformatic prediction of the C16orf57 protein structure denotes a very basic enzymatic function consistent with a housekeeping function. Detection of aberrant transcripts, also in cells from PN patients carrying early truncated mutations, suggests they might be translatable. Tissue-specific sensitivity to the lack of functionally correct protein accounts for the main cutaneous and haematological clinical signs of PN patients.</p