Langerin-Heparin Interaction: Two Binding Sites for Small and Large Ligands as revealed by a combination of NMR Spectroscopy and Cross-Linking Mapping Experiments

Langerin is a C-type lectin present on Langerhans cells that mediates capture of pathogens in a carbohydrate-dependent manner, leading to subsequent internalization and elimination in the cellular organelles called Birbeck granules. This mechanism mediated by langerin was shown to constitute a natural barrier for HIV-1 particle transmission. Besides interacting specifically with high mannose and fucosylated neutral carbohydrate structures, langerin has the ability to bind sulfated carbohydrate ligands as 6-sulfated galactosides in the Ca2+ dependent binding site. Very recently langerin was demonstrated to interact with sulfated glycosaminoglycans (GAGs), in a Ca2+ independent way, resulting in the proposal of a new binding site for GAGs. Based on those results, we have conducted a structural study of the interactions of small heparin (HEP) like oligosaccharides with langerin in solution. Heparin-bead cross-linking experiments, an approach specifically designed to identify HEP/HS binding sites in proteins were first carried out and experimentally validated the previously proposed model for the interaction of Lg ECD with 6 kDa HEP. High-resolution NMR studies of a set of 8 synthetic HEP-like trisaccharides harboring different sulfation patterns demonstrated that all of them bound to langerin in a Ca2+ dependent way. The binding epitopes were determined by STD NMR and the bound conformations by transferred NOESY experiments. These experimental data were combined with docking and molecular dynamics and resulted in the proposal of a binding mode characterized by the coordination of calcium by the two equatorial hydroxyl groups OH3 and OH4 at the non-reducing end. The binding also includes the carboxylate group at the adjacent iduronate residue. Such epitope is shared by all the 8 ligands, explaining the absence of any impact on binding from their differences in substitution pattern. Finally, in contrast to the small trisaccharides, we demonstrated that a longer HEP-like hexasaccharide, bearing an additional O-sulfate group at the non-reducing end, which precludes binding to the Ca2+ site, interacts with langerin in the previously identified Ca2+ independent binding site

Clinical and microbiological assessment of patients with a long-term diagnosis of human immunodeficiency virus infection and Candida oral colonization

The objective of this study was to evaluate Candida oral colonization in human immunodeficiency virus (HIV)-infected patients undergoing long-term highly active antiretroviral therapy (ARV). the cross-sectional study included 331 HIV patients, diagnosed from 1983 to 2003. Oral swabs were performed, and Candida species were determined using ID 32C. Isolates were tested for antifungal susceptibility. Clinical and laboratory data were collected to identify the association with Candida colonization. in total, 161 Candida isolates were detected among 147 of the 331 patients (44%), independently of the time when HIV infection was diagnosed. Candida albicans strains represented 137 (85%) of the isolates, and were susceptible to all of the tested antifungal drugs. Among the non-C. albicans strains, six isolates were dose-dependently susceptible to fluconazole, nine to itraconazole, and seven to ketoconazole. the isolation of Candida was significantly higher in patients with virological failure (83/147; p 0.0002) and CD4(+) T-lymphocyte counts < 200 cells/mm(3) (30/83; p 0.0003). Recovery of Candida in the oral cavity was independent of protease inhibitor (PI) usage (p 0.60). Colonized patients typically underwent salvage therapy (p 0.003), and had more episodes of opportunistic fungal infections (p 0.046) and malignancies (p 0.004). Oral Candida colonization in patients under ARV therapy was associated with the immunosupressed status of HIV-infected patients, i.e. low number of CD4(+) T-cells per cubic millimetre, failure of ARV therapy (salvage therapy), and higher number of opportunistic infections and malignancies. Despite the fact that PIs have in vitro antifungal activity, the use of this class of antiretroviral agent did not influence the presence of Candida in the oral cavity of AIDS patients.Univ Estadual Campinas, Dept Internal Med, Fac Med Sci, Div Infect Dis, BR-13081070 Campinas, SP, BrazilUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilChiba Univ, Med Mycol Res Ctr, Chiba, JapanUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilWeb of Scienc

Clinical and microbiological assessment of patients with a long-term diagnosis of human immunodeficiency virus infection and Candida oral colonization

The objective of this study was to evaluate Candida oral colonization in human immunodeficiency virus (HIV)-infected patients undergoing long-term highly active antiretroviral therapy (ARV). the cross-sectional study included 331 HIV patients, diagnosed from 1983 to 2003. Oral swabs were performed, and Candida species were determined using ID 32C. Isolates were tested for antifungal susceptibility. Clinical and laboratory data were collected to identify the association with Candida colonization. in total, 161 Candida isolates were detected among 147 of the 331 patients (44%), independently of the time when HIV infection was diagnosed. Candida albicans strains represented 137 (85%) of the isolates, and were susceptible to all of the tested antifungal drugs. Among the non-C. albicans strains, six isolates were dose-dependently susceptible to fluconazole, nine to itraconazole, and seven to ketoconazole. the isolation of Candida was significantly higher in patients with virological failure (83/147; p 0.0002) and CD4(+) T-lymphocyte counts < 200 cells/mm(3) (30/83; p 0.0003). Recovery of Candida in the oral cavity was independent of protease inhibitor (PI) usage (p 0.60). Colonized patients typically underwent salvage therapy (p 0.003), and had more episodes of opportunistic fungal infections (p 0.046) and malignancies (p 0.004). Oral Candida colonization in patients under ARV therapy was associated with the immunosupressed status of HIV-infected patients, i.e. low number of CD4(+) T-cells per cubic millimetre, failure of ARV therapy (salvage therapy), and higher number of opportunistic infections and malignancies. Despite the fact that PIs have in vitro antifungal activity, the use of this class of antiretroviral agent did not influence the presence of Candida in the oral cavity of AIDS patients.Univ Estadual Campinas, Dept Internal Med, Fac Med Sci, Div Infect Dis, BR-13081070 Campinas, SP, BrazilUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilChiba Univ, Med Mycol Res Ctr, Chiba, JapanUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilWeb of Scienc

Fiber-optic lossy mode resonance sensors

In the last 4 years, experimental evidences about the potential use of optical sensors based on Lossy Mode Resonances (LMR) have been presented in the literature. These LMR sensors have some similarities with Surface Plasmon Resonance (SPR) sensors, the gold standard in label-free, real-time biomolecular interaction analysis. In these new LMR sensors, if the non-metallic nanocladding of an optical waveguide fulfills the conditions explained in this work, coupling of light to the cladding modes happens at certain resonance wavelengths, which enables the use of LMR devices as refractometers and opens the door to diverse applications such as in biology and proteomics research. These highly sensitive refractometers have already shown sensitivities higher than 20,000 nm/RIU or 5x10-7 RIU and, given the youth of this field, it is expected to achieve even better values

Optical sensors based on lossy-mode resonances

Lossy-mode resonance (LMR)–based optical sensing technology has emerged in the last two decades as a nanotechnological platform with very interesting and promising properties. LMR complements the metallic materials typically used in surface plasmon resonance (SPR)–based sensors, with metallic oxides and polymers. In addition, it enables one to tune the position of the resonance in the optical spectrum, to excite the resonance with both transverse electric (TE) and transverse magnetic (TM) polarized light, and to generate multiple resonances. The domains of application are numerous: as sensors for detection of refractive indices voltage, pH, humidity, chemical species, and antigens, as well as biosensors. This review will discuss the bases of this relatively new technology and will show the main contributions that have permitted the optimization of its performance to the point that the question arises as to whether LMR–based optical sensors could become the sensing platform of the near future

Comparative gastrointestinal organ lengths among Amazonian primates (Primates: Platyrrhini)

ObjectivesThe morphological features of the gastrointestinal tract (GIT) in mammals reflect a species' food niche breadth and dietary adaptations. For many wild mammals, the relationship between the structure of the GIT and diet is still poorly understood, for example, the GIT for frugivorous primates is usually classified as unspecialized and homogeneous. Here, we compare the GIT structure of 13 primate species from the three families of extant platyrrhines (Atelidae, Pitheciidae, and Cebidae) in Amazonia, and discuss possible evolutionary adaptations to different diets and trophic niches.MethodsWe measured the length of the esophagus, stomach, small intestine, large intestine, cecum, colon, and rectum of the digestive tracts of 289 primate specimens. We determined the allometric relationships of the different tubular organs with the total length of the GIT as a proxy of specimen body size. Allometric parameters were used to establish the quotients of differentiation of every organ for each primate specimen.ResultsThere was a high differentiation in structure of the digestive organs among genera. Alouatta specimens clearly separated from the other genera based on dissimilarities in gastric, colonic, and rectal quotients, likely linked to the fermentation of plant contents. In contrast, all cebines (Sapajus, Cebus, and Saimiri) and Cacajao species had similar small intestine quotients, which is expected due to their high rates of animal matter consumed.ConclusionsWe show that diverse adaptations in digestive structure exist among frugivorous primates, which in turn reflect different dietary patterns within this group that may enable the geographic coexistence of different primate species

Opsoclonus-myoclonus-ataxia syndrome associated with chikungunya and dengue virus co-infection

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-09-19T16:55:58Z No. of bitstreams: 1 Rosario MS Opsoclonus-Myoclonus-Ataxia Syndrome....pdf: 514736 bytes, checksum: 2d645cdbe4121ce8c8d637e1a2c7ed2d (MD5) Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-09-19T17:27:26Z (GMT) No. of bitstreams: 1 Rosario MS Opsoclonus-Myoclonus-Ataxia Syndrome....pdf: 514736 bytes, checksum: 2d645cdbe4121ce8c8d637e1a2c7ed2d (MD5) Made available in DSpace on 2018-09-19T17:27:26Z (GMT). No. of bitstreams: 1 Rosario MS Opsoclonus-Myoclonus-Ataxia Syndrome....pdf: 514736 bytes, checksum: 2d645cdbe4121ce8c8d637e1a2c7ed2d (MD5) Previous issue date: 2018 CNPq-National Council for Scientific and Technological Development (302584/2015-3) and MCTI-Ministry of Science, Technology, Innovation/FINEP–Funding Authority for Studies and Projects/FNDCT–National Fund for the Development of Science and Technology (04160060-00/2016) Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Secretaria Estadual da Saúde da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / University of Rome Tor Vergata. Rome, Italy Secretaria Estadual da Saúde da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil Secretaria Estadual da Saúde da Bahia. Hospital Geral Roberto Santos. Salvador, BA, Brasil University of Oxford. Department of Zoology. Oxford, UK Instituto Evandro Chagas. Centro de Tecnologia e Inovação. Ananindeua, PA, Brasil Instituto Evandro Chagas. Centro de Tecnologia e Inovação. Ananindeua, PA, Brasil Instituto Evandro Chagas. Centro de Tecnologia e Inovação. Ananindeua, PA, Brasil Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare neurological disorder characterized by irregular multidirectional eye movements, myoclonus, cerebellar ataxia, sleep disturbances, and cognitive dysfunction. Although most commonly related to paraneoplastic syndrome, this condition has occasionally been described following infectious illnesses. This article reports the first case of OMAS in association with chikungunya and dengue virus co-infection. The genetic analysis identified chikungunya virus of East/Central/South African genotype and dengue serotype 4 virus of genotype II. This report represents an unusual clinical syndrome associated with viral co-infection and reinforces the need for clinical vigilance with regard to neurological syndromes in the context of emergent arboviruses

O uso de diários de campo na reflexão sobre a prática docente de licenciandos de química

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Quasi-elastic processes of the 48Ca + 120Sn system and the 48Ca nuclear matter density

We present the results of a high-precision quasi-elastic excitation function measurement for the 48Ca + 120Sn system at θLAB = 160 at near-barrier energies in steps of 1.0 MeV. The corresponding quasi-elastic barrier distribution is derived. A large-scale coupled-channel calculation was performed to investigate the role of several reaction channels in the reaction mechanism. An excellent agreement between theory and data was obtained for the barrier distribution. The first quadrupole vibrations of the 48Ca and 120Sn, the 2n, and the 4He transfers have a strong influence on the reaction mechanism and are responsible for the good agreement achieved. The 1n transfer has a minor importance in the result when compared with the 2n transfer, which suggests that the pairing correlation might play an important role in the 2n-neutron transfer process. However, if the octupole vibration of the projectile is included in the coupling scheme, the agreement with the data gets worse. The comparison of the coupled-channel calculations with experimental data leads to the conclusion that the nuclear matter diffuseness of the 48Ca nucleus is 0.56 fm in agreement with most of the double-magic nuclei.European Community 26201

Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD