Stigmergy in Web 2.0 : a model for site dynamics

Building Web 2.0 sites does not necessarily ensure the success of the site. We aim to better understand what improves the success of a site by drawing insight from biologically inspired design patterns. Web 2.0 sites provide a mechanism for human interaction enabling powerful intercommunication between massive volumes of users. Early Web 2.0 site providers that were previously dominant are being succeeded by newer sites providing innovative social interaction mechanisms. Understanding what site traits contribute to this success drives research into Web sites mechanics using models to describe the associated social networking behaviour. Some of these models attempt to show how the volume of users provides a self-organising and self-contextualisation of content. One model describing coordinated environments is called stigmergy, a term originally describing coordinated insect behavior. This paper explores how exploiting stigmergy can provide a valuable mechanism for identifying and analysing online user behavior specifically when considering that user freedom of choice is restricted by the provided web site functionality. This will aid our building better collaborative Web sites improving the collaborative processes.

Cytokine synthesis by intestinal intraepithelial lymphocytes. Both gamma/delta T cell receptor-positive and alpha/beta T cell receptor-positive T cells in the G1 phase of cell cycle produce IFN-gamma and IL-5

Murine intestinal intraepithelial lymphocytes (IEL) have been shown to contain subsets of alpha/beta TCR+ and gamma/delta TCR+ T cells that spontaneously produce cytokines such as IFN-gamma and IL-5. We have now determined the nature and cell cycle stage of these cytokine-producing T lymphocytes in EIL by using IFN-gamma- and IL-5-specific ELISPOT assay, cytokine-specific mRNA-cDNA dot-blot hybridization and polymerase chain reaction, and flow cytometry (FACS) for DNA analysis. When CD3+ T cells from IEL of normal C3H/HeN mice were separated into low and high density fractions by discontinuous Percoll gradients, IFN-gamma and IL-5 spot-forming cells were only found in the former population. Analysis of mRNA for these cytokines by both IFN-gamma- and IL-5-specific dot-blot hybridization and polymerase chain reaction revealed that higher levels of message for IFN-gamma and IL-5 were also seen in the low density fraction. However, cell cycle analysis of these two fractions by FACS using propidium iodide showed a similar pattern of cell cycle stages in both low and high density populations (G0 + G1 approximately 96 to 98% and S/G2 + M approximately 2 to 4%). Finally, mRNA from gamma/delta TCR+ and alpha/beta TCR+ T cells in both low and high density fractions of IEL were analyzed for IFN-gamma and IL-5 message by polymerase chain reaction. After 35 cycles of amplification, both gamma/delta TCR+ and alpha/beta TCR+ T cells in the low density fraction expressed higher levels of message for these two cytokines when compared with the high density population. These results have now shown that both gamma/delta and alpha/beta TCR+ IEL can be separated into low and high density subsets and both fractions possess a similar stage of cell cycle. However, only the low density cells (in G1 phase) of both gamma/delta and alpha/beta TCR types possess increased cytokine-specific mRNA and produce the cytokines IFN-gamma and IL-5. Our results suggest that alpha/beta TCR+ and gamma/delta TCR+ IEL can produce cytokines without cell proliferation.

A novel immunodeficiency disorder characterized by genetic amplification of interleukin 25

Many primary immunodeficiency disorders of differing etiologies have been well characterized, and much understanding of immunological processes has been gained by investigating the mechanisms of disease. Here, we have used a whole-genome approach, employing single-nucleotide polymorphism and gene expression microarrays, to provide insight into the molecular etiology of a novel immunodeficiency disorder. Using DNA copy number profiling, we define a hyperploid region on 14q11.2 in the immunodeficiency case associated with the interleukin (IL)-25 locus. This alteration was associated with significantly heightened expression of IL25 following T-cell activation. An associated dominant type 2 helper T cell bias in the immunodeficiency case provides a mechanistic explanation for recurrence of infections by pathogens met by Th1-driven responses. Furthermore, this highlights the capacity of IL25 to alter normal human immune responses.

IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF

Background IL-20 is a pleiotrophic member of the IL-10 family and plays a role in skin biology and the development of haematopoietic cells. Recently, IL-20 has been demonstrated to have potential anti-angiogenic effects in non-small cell lung cancer (NSCLC) by down regulating COX-2. Methods The expression of IL-20 and its cognate receptors (IL-20RA/B and IL-22R1) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of this family was examined in normal bronchial epithelial and NSCLC cell lines. Furthermore, the effect of IL-20 on VEGF family members was examined. Results The expression of IL-20 and its receptors are frequently dysregulated in NSCLC. IL-20RB mRNA was significantly elevated in NSCLC tumours (p < 0.01). Protein levels of the receptors, IL-20RB and IL-22R1, were significantly increased (p < 0.01) in the tumours of NSCLC patients. IL-20 and its receptors were found to be epigenetically regulated through histone post-translational modifications and DNA CpG residue methylation. In addition, treatment with recombinant IL-20 resulted in decreased expression of the VEGF family members at the mRNA level. Conclusions This family of genes are dysregulated in NSCLC and are subject to epigenetic regulation. Whilst the anti-angiogenic properties of IL-20 require further clarification, targeting this family via epigenetic means may be a viable therapeutic option in lung cancer treatment. © 2011 Elsevier Ltd. All rights reserved.

A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk

The main genetic determinant of soluble interleukin 6 receptor (sIL-6R) levels is the missense variant rs2228145 that maps to the cleavage site of IL-6R. For each Ala allele, sIL-6R serum levels increase by ∼20 ng ml -1 and asthma risk by 1.09-fold. However, this variant does not explain the total heritability for sIL-6R levels. Additional independent variants in IL6R may therefore contribute to variation in sIL-6R levels and influence asthma risk. We imputed 471 variants in IL6R and tested these for association with sIL-6R serum levels in 360 individuals. An intronic variant (rs12083537) was associated with sIL-6R levels independently of rs4129267 (P=0.0005), a proxy single-nucleotide polymorphism for rs2228145. A significant and consistent association for rs12083537 was observed in a replication panel of 354 individuals (P=0.033). Each rs12083537:A allele increased sIL-6R serum levels by 2.4 ng ml -1. Analysis of mRNA levels in two cohorts did not identify significant associations between rs12083537 and IL6R transcription levels. On the other hand, results from 16 705 asthmatics and 30 809 controls showed that the rs12083537:A allele increased asthma risk by 1.04-fold (P=0.0419). Genetic risk scores based on IL6R regulatory variants may prove useful in explaining variation in clinical response to tocilizumab, an anti-IL-6R monoclonal antibody.

Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case-control study and meta-analysis of published series

Objectives. It has been shown previously that IL-23R variants are associated with AS. We conducted an extended analysis in the UK population and a meta-analysis with the previously published studies, in order to refine these IL-23R associations with AS. Methods. The UK case-control study included 730 new cases and 1331 healthy controls. In the extended study, the 730 cases were combined with 1088 published cases. Allelic associations were analysed using contingency tables. In the meta-analysis, 3482 cases and 3150 controls from four different published studies and the new UK cases were combined. DerSimonian-Laird test was used to calculate random effects pooled odds ratios (ORs). Results. In the UK case-control study with new cases, four of the eight SNPs showed significant associations, whereas in the extended UK study, seven of the eight IL-23R SNPs showed significant associations (P < 0.05) with AS, maximal with rs11209032 (P < 10-5, OR 1.3), when cases with IBD and/or psoriasis were excluded. The meta-analysis showed significant associations with all eight SNPs; the strongest associations were again seen not only with rs11209032 (P = 4.06 × 10-9, OR ∼1.2) but also with rs11209026 (P < 10-10, OR ∼0.6). Conclusions. IL-23R polymorphisms are clearly associated with AS, but the primary causal association(s) is(are) still not established. These polymorphisms could contribute either increased or decreased susceptibility to AS; functional studies will be required for their full evaluation. Additionally, observed stronger associations with SNPs rs11209026 and rs11465804 upon exclusion of IBD and/or psoriasis cases may represent an independent association with AS. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Axial binding of 2-methylimidazole to the tetraarylcarboxylatodiruthenium (II, III) core: X-ray crystal structure of [Ru-2(O2CC6H4-p-OMe)(4)(2-mimH)(2)](ClO4). 1.75CH(2)Cl(2).H2O

Diruthenium (II. III) complexes of the type [Ru-2(O2CAr)(4) (2-mimH)(2)](ClO4) (Ar = C6H4-p-X : X=OMe,1, X=Me, 2, 2-mimH=2-methylimidazole) have been isolated from the reaction of Ru2Cl(O2CAr)(4) with 2-mimH in CH2Cl2 followed by the addition of NaClO4. The crystal structure of 1.1.75CH(2)Cl(2).H2O has been determined. The crystal belongs to the monoclinic space group p2(1)/c with the following unit cell dimensions for the C40H40N4O16ClRu2.1.75CH(2)Cl(2).H2O (M = 1237.0) : a = 12.347(3)Angstrom, b = 17.615(5)Angstrom, c = 26.148(2)Angstrom,beta = 92.88(1)degrees. v = 5679(2)Angstrom(3). Z=4, D-c = 1.45 g cm(-3). lambda(Mo-K-alpha) = 0.7107 Angstrom, mu(Mo-K-alpha) = 8.1 cm(-1), T = 293 K, R = 0.0815 (wR(2) = 0.2118) for 5834 reflections with 1 > 2 sigma(I). The complex has a tetracarboxylatodiruthenium (II, III) core and two axially bound 2-methylimidazole ligands. The Ru-Ru bond length is 2.290(1)Angstrom. The Ru-Ru bond order is 2.5 and the complex is three-electron paramagnetic. The complex shows an irreversible Ru-2(II,III)-->Ru-2(Il,II) reduction near -0.2 V vs SCE in CH2Cl2-0. 1 MTBAP. The complexes exemplify the first adduct of the tetracarboxylatodiruthenium (II,III) core having N-donor ligands

Influence of interleukin-1 beta on platelet-poor plasma clot formation: A potential impact on early bone healing

Objectives Hematoma quality (especially the fibrin matrix) plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β) on fibrin clot formation from platelet-poor plasma (PPP). Methods Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG), blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM), confocal microscopy (CM), turbidity, and clot lysis assays. Results The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β) compared to the control group without IL-1β (543.8 ± 205.8). Maximal turbidity was observed in the control group. IL-1β (500 pg/mL) treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05). The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers. Conclusion IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

Cystine peptides Antiparallel β-sheet conformation of the cyclic biscystine peptide [Boc-Cys-Ala-Cys-NHCH3]2

The crystal structure analysis of the cyclic biscystine peptide [Boc-Cys1-Ala2-Cys3-NHCH3]2 with two disulfide bridges confirms the antiparallel ?-sheet conformation for the molecule as proposed for the conformation in solution. The molecule has exact twofold rotation symmetry. The 22-membered ring contains two transannular NH ? OC hydrogen bonds and two additional NH ? OC bonds are formed at both ends of the molecule between the terminal (CH3)3COCO and NHCH3 groups. The antiparallel peptide strands are distorted from a regularly pleated sheet, caused mainly by the L-Ala residue in which ?=� 155° and ?= 162°. In the disulfide bridge C? (1)-C? (1)-S(1)-(3')-C?(3')-C?(3'), S�S = 2.030 Å, angles C? SS = 107° and 105°, and the torsional angles are �49, �104, +99, �81, �61°, respectively. The biscystine peptide crystallizes in space group C2 with a = 14.555(2) Ã…, b = 10.854(2) Ã…, c = 16.512(2)Ã…, and ?= 101.34(1) with one-half formula unit of C30H52N8O10S4· 2(CH3)2SO per asymmetric unit. Least-squares refinement of 1375 reflections observed with |F| > 3?(F) yielded an R factor of 7.2%.

A combined extended and helical backbone for Boc-(Ala-Leu-Ac(7)c-)(2)-OMe

The structure of the peptide Boc-Ala-Leu-Ac(7)c-Ala-Leu-Ac(7)c-OMe (Ac(7)c,1-aminocycloheptane-1-carboxylic acid) is described in crystals. The presence of two Ac(7)c residues was expected to stabilize a 3(10)-helical fold. Contrary to expectation the structural analysis revealed an unfolded amino terminus, with Ala(1) adopting an extended beta-conformation (phi = -93degrees,psi = 112degrees). Residues 2-5 form a 3(10)-helix, stabilized by three successive intramolecular hydrogen bonds. Notably, two NH groups Ala(1) and Ac(7)c(3) do not form any hydrogen bonds in the crystal. Peptide assembly appears to be dominated by packing of the cycloheptane rings that stack against one another within the molecule and also throughout the crystal in columns.

Ac2PIM-responsive miR-150 and miR-143 Target Receptor-interacting Protein Kinase 2 and Transforming Growth Factor Beta-activated Kinase 1 to Suppress NOD2-induced Immunomodulators

Specific and coordinated regulation of innate immune receptor-driven signaling networks often determines the net outcome of the immune responses. Here, we investigated the cross-regulation of toll-like receptor (TLR)2 and nucleotide-binding oligomerization domain (NOD)2 pathways mediated by Ac2PIM, a tetra-acylated form of mycobacterial cell wall component and muramyl dipeptide (MDP), a peptidoglycan derivative respectively. While Ac2PIM treatment of macrophages compromised their ability to induce NOD2-dependent immunomodulators like cyclooxygenase (COX)-2, suppressor of cytokine signaling (SOCS)-3, and matrix metalloproteinase (MMP)-9, no change in the NOD2-responsive NO, TNF-alpha, VEGF-A, and IL-12 levels was observed. Further, genome-wide microRNA expression profiling identified Ac2PIM-responsive miR-150 and miR-143 to target NOD2 signaling adaptors, RIP2 and TAK1, respectively. Interestingly, Ac2PIM was found to activate the SRC-FAK-PYK2-CREB cascade via TLR2 to recruit CBP/P300 at the promoters of miR-150 and miR-143 and epigenetically induce their expression. Loss-of-function studies utilizing specific miRNA inhibitors establish that Ac2PIM, via the miRNAs, abrogate NOD2-induced PI3K-PKC delta-MAPK pathway to suppress beta-catenin-mediated expression of COX-2, SOCS-3, and MMP-9. Our investigation has thus underscored the negative regulatory role of Ac2PIM-TLR2 signaling on NOD2 pathway which could broaden our understanding on vaccine potential or adjuvant utilities of Ac2PIM and/or MDP.

Sonic hedgehog-responsive lipoxygenases and cyclooxygenase-2 modulate Dectin-1-induced inflammatory cytokines

Immune responses during fungal infections are predominately mediated by 5/15-lipoxygenases (LO)-or cyclooxygenase (COX)-2-catalysed bioactive eicosanoid metabolites like leukotrienes, lipoxins and prostaglandins. Although few host mediators of fungi-triggered eicosanoid production have been established, the molecular mechanism of expression and regulation of 5-LO, 15-LO and COX-2 are not well-defined. Here, we demonstrate that, macrophages infected with representative fungi Candida albicans, Aspergillus flavus or Aspergillus fumigatus or those treated with Curdlan, a selective agonist of pattern recognition receptor for fungi Dectin-1, displays increased expression of 5-LO, 15-LO and COX-2. Interestingly, Dectin-1-responsive Syk pathway activates mTOR-sonic hedgehog (SHH) signaling cascade to stimulate the expression of these lipid metabolizing enzymes. Loss-of-function analysis of the identified intermediaries indicates that while Syk-mTOR-SHH pathway-induced 5-LO and 15-LO suppressed the Dectin-l-responsive pro-inflammatory signature cytokines like TNE-alpha, IL-1 beta and IL-12, Syk-mTOR-SHH-induced COX-2 positively regulated these cytokines. Dectin-1-stimulated IL-6, however, is dependent on 5-LO, 15-LO and COX-2 activity. Together, the current study establishes Dectin-1-arbitrated host mediators that direct the differential regulation of immune responses during fungal infections and thus are potential candidates of therapeutic intervention. (C) 2015 Elsevier Ltd. All rights reserved.

Contos da Câmara 2 : depoimentos de servidores nos 180 anos do Legislativo

Reúne depoimentos de servidores da Câmara do Deputados sobre os acontecimentos que marcaram a história do parlamento brasileiro a partir da segunda metade do século XX. Coletados pelo Núcleo de História Oral da Câmara durante as comemorações dos 180 anos do Poder Legislativo em 2003, os textos retratam a realidade dos primeiros anos vividos no Planalto Central: a carência de infra-estrutura, a falta de opção de atividades de lazer e o profundo sentimento de saudade da antiga capital da República. Mas também levam a reminiscências de momentos divertidos, curiosidades e reflexões animadas e esperançosas sobre a mudança da capital para Brasília. O ponto alto são as experiências vivenciadas nos prédios do Congresso Nacional, a lembrança dos amigos, dos colegas e, especialmente, dos fatos marcantes, que sublinham as significativas mudanças nas rotinas de trabalho da Instituição para se adequar à modernização e às novas exigências da sociedade, no contexto de acontecimentos políticos que modificaram seguidas vezes o cenário do país.

Catálogo de obras raras da Biblioteca da Câmara dos Deputados, v.2 : Brasil por escrito

Traz somente obras referentes ao Brasil. Inclui desde livros do século XVI, até alguns poucos do inicio do século XX. Oferece um panorama da história do Brasil desde o seu descobrimento até a Proclamação da República e da fixação definitiva das fronteiras brasileiras pelo trabalho do Barão do Rio Branco e de Joaquim Nabuco. Alguns assuntos históricos são representados, como a documentação sobre a escravatura de negros e de índios, as lutas contra os holandeses e o processo da independência. Traz a correspondência entre o Príncipe Regente Dom Pedro e seu pai, Dom João Vl, complementada por ofícios e documentos das diversas províncias e por depoimentos de militares portugueses submetidos a conselhos de guerra que questionaram as suas atuações ao longo do processo. Essas publicações são particularmente raras por lerem sido impressas pelas Cortes de Lisboa para ditribuição somente aos seus membros e proibida a reprodução.