Impact of Truncated O-glycans in Gastric-Cancer-Associated CD44v9 Detection

CD44 variant isoforms are often upregulated in cancer and associated with increased aggressive tumor phenotypes. The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells. Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies. However, the structural variability conferred by both the alternative splicing and CD44 protein glycosylation is disregarded. In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies. We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection. These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE, grant numbers POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-007274; OCI-01-0145-FEDER-031028; and national funds through the Foundation for Science and Technology (FCT), grant numbers PTDC/BBB-EBI/0567/2014 (to CAR), UID/BIM/04293/2013, and PTDC/MED-QUI/29780/2017; and the project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). F. Pinto received a fellowship from FCT (SFRH/BPD/115730/2016)

Diastereoselective synthesis of beta-aminosulfones from the 1,2-addition to N-(para-methoxyphenyl) imines

The base-promoted 1,2-addition of alkyl phenylsulfones to N-(para-methoxyphenyl) imines was investigated as a direct route to stereochemically defined β-aminosulfones. Using nBuLi as base, 2-(phenylsulfonyl)ethylbenzene was added to a range of N-(para-methoxyphenyl) imines to give β-aminosulfone products in high yields as single anti-diastereoisomers. Other less substituted alkyl phenylsulfones were not as successful

Stereoselective synthesis of 1,2-diamine containing indolines by a conjugate addition nitro-Mannich reaction.

A conjugate addition nitro-Mannich reaction followed by nitro reduction and intramolecular N-arylation gives diastereomerically pure substituted 1,2-diamine containing indolines. Placing the N-arylation cyclisation handle on the imine precursor derived from an ortho-bromine substituted aromatic aldehyde gave the corresponding β-nitroamines in 55-72% yields as single diastereoisomers. Nitro reduction was effected with modified quantities of Zn/HCl and a subsequent Pd(0) catalysed Buchwald Hartwig cyclisation gave indoline products in 40-70% yields as single diastereoisomers

Base-Controlled Diastereoselective Synthesis of Either anti- or syn-β-Aminonitriles

Deprotonation of secondary alkane nitriles with nBuLi and addition to aryl imines gives kinetic anti-β-aminonitriles. Use of LHMDS allows reversible protonation of the reaction intermediate to give syn-β-aminonitriles. The pure diastereosiomers can be isolated in good yields, and the mechanism was elucidated

Upper tropospheric ozone production from lightning NOx-impacted convection: Smoke ingestion case study from the DC3 campaign

©2015. American Geophysical Union. All Rights Reserved. As part of the Deep Convective Cloud and Chemistry (DC3) experiment, the National Science Foundation/National Center for Atmospheric Research (NCAR) Gulfstream-V (GV) and NASA DC-8 research aircraft probed the chemical composition of the inflow and outflow of two convective storms (north storm, NS, south storm, SS) originating in the Colorado region on 22 June 2012, a time when the High Park wildfire was active in the area. A wide range of trace species were measured on board both aircraft including biomass burning (BB) tracers hydrogen cyanide (HCN) and acetonitrile (ACN). Acrolein, a much shorter lived tracer for BB, was also quantified on the GV. The data demonstrated that the NS had ingested fresh smoke from the High Park fire and as a consequence had a higher VOC OH reactivity than the SS. The SS lofted aged fire tracers along with other boundary layer ozone precursors and was more impacted by lightning NOx (LNOx) than the NS. The NCAR master mechanism box model was initialized with measurements made in the outflow of the two storms. The NS and SS were predicted to produce 11 and 14ppbv of O3, respectively, downwind of the storm over 2days. Sensitivity tests revealed that the ozone production potential of the SS was highly dependent on LNOx. Normalized excess mixing ratios, ΔX/ΔCO, for HCN and ACN were determined in both the fire plume and the storm outflow and found to be 7.0±0.5 and 2.3±0.5pptvppbv-1, respectively, and 1.4±0.3pptvppbv-1 for acrolein in the outflow only

Reductive conjugate addition nitro-Mannich route for the stereoselective synthesis of 1,2,3,4-tetrahydroquinoxalines

A concise, high yielding and structurally divergent synthesis of complex 1,2,3,4-tetrahydroquinoxalines with excellent diastereoselectivity is described. A wide array of nitroalkenes and imines derived from commercially available aromatic aldehydes and 2-chloroanalines were subjected to a key reductive conjugate addition nitro-Mannich reaction to give diastereomerically pure β-nitro amines. Sequential reduction of the nitro function followed by Pd-catalyzed intramolecular N-arylation of the resultant primary amine onto the 2-chloroanailine gives highly substituted 1,2,3,4-tetrahydroquinoxalines. Non basic imines were found to participate better in the nitro-Mannich reaction if the stronger acid methanesulfonic acid was used to promote the reaction. The 3 step reaction sequence should be useful for the array synthesis of drug like scaffolds

Genetic variability in five populations of Partamona helleri (Hymenoptera, Apidae) from Minas Gerais State, Brazil

Partamona is a Neotropical genus of stingless bees that comprises 33 species distributed from Mexico to southern Brazil. These bees are well-adapted to anthropic environments and build their nests in several substrates. In this study, 66 colonies of Partamona helleri from five localities in the Brazilian state of Minas Gerais (São Miguel do Anta, Teixeiras, Porto Firme, Viçosa and Rio Vermelho) were analyzed using nine microsatellite loci in order to assess their genetic variability. Low levels of observed (Ho = 0.099-0.137) and expected (H e = 0.128-0.145) heterozygosity were encountered and revealed discrete genetic differentiation among the populations (F ST = 0.025). AMOVA further showed that most of the total genetic variation (94.24%) in P. helleri was explained by the variability within local populations

Host immunity in the protective response to nasal immunization with a pneumococcal antigen associated to live and heat-killed Lactobacillus casei

Background: At present, available pneumococcal vaccines have failed to eradicate infections caused by S. pneumoniae. Search for effective vaccine continues and some serotype independent pneumococcal proteins are considered as candidates for the design of new vaccines, especially a mucosal vaccine, since pneumococci enter the body through mucosal surfaces. Selection of the appropriate adjuvant is important for mucosal vaccines, and lactic acid bacteria (LAB) with immunostimulant properties are promissory candidates. In this work, we assessed the adjuvant effect of a probiotic strain, Lactobacillus casei (L. casei), when nasally administered with a pneumococcal antigen (pneumococcal protective protein A: PppA) for the prevention of pneumococcal infection. Adjuvanticity of both live (LcV) and heat-killed (LcM) was evaluated and humoral and cellular antigen-specific immune response was assessed in mucosal and systemic compartments. The potential mechanisms induced by nasal immunization were discussed.Results: Nasal immunization of young mice with PppA+LcV and PppA+LcM induced anti-PppA IgA and IgG antibodies in mucosal and systemic compartments and levels of these specific antibodies remained high even at day 45 after the 3rd Immunization (3rd I). These results were correlated with IL-4 induction by the mixture of antigen plus LcV and LcM. Also, PppA+Lc (V and M) induced stimulation of Th1 and Th17 cells involved in the defence against pneumococci. The protection against pneumococcal respiratory challenge at day 30 after the 3rd I showed that PppA+LcV and PppA+LcM immunizations significantly reduced pathogen counts in nasal lavages while prventing their passage into lung and blood. Survival of mice immunized with the co-application of PppA plus LcV and LcM was significantly higher than in mice immunized with PppA alone and control mice when intraperitoneal challenge was performed. No significant differences between the treatments involving LcV and LcM were found.Conclusions: Live and heat-killed L. casei enhanced the antigen-specific immune response when administered nasally with a pneumococcal antigen. Considering the potential risk associated with live bacteria, the design of a nasal vaccine based on pneumococcal antigens and heat-killed L. casei emerges as a safe and effective strategy for the prevention of pneumococcal infections and opens new possibilities of application of dead LAB as adjuvants in vaccine formulations against other pathogens.Fil: Vintiñi, Elisa Ofelia. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Medina, Marcela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentin