MARSI: metabolite analogues for rational strain improvement

Metabolite analogues (MAs) mimic the structure of native metabolites, can competitively inhibit their utilization in enzymatic reactions, and are commonly used as selection tools for isolating desirable mutants of industrial microorganisms. Genome-scale metabolic models representing all biochemical reactions in an organism can be used to predict effects of MAs on cellular phenotypes. Here, we present the Metabolite Analogues for Rational Strain Improvement (MARSI) framework. MARSI provides a rational approach to strain improvement by searching for metabolites as targets instead of genes or reactions. The designs found by MARSI can be implemented by supplying MAs in the culture media, enabling metabolic rewiring without the use of recombinant DNA technologies that cannot always be used due to regulations. To facilitate experimental implementation, MARSI provides tools to identify candidate MAs to a target metabolite from a database of known drugs and analogues

Anéis vasculares na infância: diagnóstico e tratamento

Objetivo: apresentar a experiência do Serviço de Cirurgia Pediátrica do Instituto da Criança do HCFMUSP no diagnóstico e tratamento de crianças com anomalias do arco aórtico e definir a importância dos exames complementares para o diagnóstico. Métodos: estudo retrospectivo de 22 crianças com diagnóstico de compressão traqueoesofágica por anel vascular tratadas no Instituto da Criança, no período de 1985 a 2000, investigando-se dados clínicos pré e pós-operatórios, exames complementares e evolução. Resultados: a anomalia vascular mais freqüente foi artéria inominada direita anômala (10 casos), seguido de duplo arco aórtico (7 casos) e arco aórtico à direita (5 casos). Os sintomas predominantes foram respiratórios (86%) e de início precoce (76% desde o período neonatal). Entretanto, o diagnóstico definitivo na maioria dos casos (60%) só foi estabelecido após 1 ano de vida. O exame mais importante para o diagnóstico foi o esofagograma. A correção de todas anomalias foi realizada por toracotomia póstero-lateral esquerda. Não ocorreram complicações cirúrgicas. A evolução foi pior nos casos operados mais tardiamente. Todas as crianças permaneceram sintomáticas por até 6 meses, apesar de significativa melhora no pós-operatório. Conclusão: o diagnóstico de anel vascular deve ser investigado nas crianças com sintomas respiratórios de início precoce e nas "chiadoras" de difícil controle. O diagnóstico pode ser realizado de forma simples através do esofagograma. Os demais exames de imagem acrescentam poucas informações e são dispensáveis na maioria dos casos. Os sintomas respiratórios podem persistir com menor intensidade por períodos variáveis no pós-operatório.<br>Objective: To present the study carried out by the Pediatric Surgery Department of Instituto da Criança at the Medical School of Universidade de São Paulo regarding the diagnosis and treatment of children with aortic arch abnormalities and to define the role of complementary exams for diagnosis. Methods: Retrospective study of 22 patients with diagnosis of tracheoesophageal compression treated at Instituto da Criança from 1985 to 2000, analyzing pre- and postoperative clinical data, diagnostic exams and outcome. Results: The most frequent diagnosis was right aberrant innominate artery (10 cases), followed by double aortic arch (7 cases) and right aortic arch (5 cases). Respiratory symptoms (86%) and early manifestation (76% since the neonatal period) were predominant. Nevertheless, most cases (60%) had the definitive diagnosis established only after 1 year of life. The most relevant examination for the diagnosis was the esophagogram. The correction of all the anomalies was carried out through left postero-lateral thoracotomy. There were no surgical complications. The outcome was worse in patients with delayed treatment. All children remained symptomatic for up to 6 months, although they had significant improvement in the postoperative period. Conclusions: The diagnosis of vascular rings should be considered in children with early respiratory symptoms and in the wheezing baby with difficult control. The diagnosis may be established just through the esophagogram. Other image studies add few information and they are unnecessary in most cases. Less severe symptoms may persist for variable periods

Magnetoliposomes containing magnesium ferrite nanoparticles for enhanced therapeutic potential of curcumin

In this work, magnesium ferrite nanoparticles with superparamagnetic behavior and sizes around 20 nm were prepared and characterized. The structural and magnetic properties of these nanoparticles were evaluated by XRD, SEM and SQUID. In order to further develop applications in cancer therapy, the prepared MgFe2O4 nanoparticles were covered with a lipid bilayer (solid magnetoliposomes) or incorporated in lipid vesicles, forming aqueous magnetoliposomes.info:eu-repo/semantics/publishedVersio

Development of a Questionnaire to Assess Knowledge and Perceptions about Edible Insects

Edible insects (EI) have been consumed as traditional foods in many parts of the globe, but in other regions, they are not readily accepted, particularly in Western countries. However, because EI are suggested to constitute a more sustainable protein food as compared with other sources of animal protein, they can be considered a future food that could help mitigate hunger and malnutrition. Additionally, new gastronomic trends are already targeting this area for exploring new potentialities. The objective of this work was to develop and validate a questionnaire to assess consumers’ perceptions and knowledge about EI in seven different domains: D1. Culture and Tradition, D2. Gastronomic Innovation and Gourmet Kitchen, D3. Environment and Sustainability, D4. Economic and Social Aspects, D5. Commercialization and Marketing, D6. Nutritional Aspects and D7. Health Effects. The 64 items were subjected to item analysis and reliability analysis for validation, and factor analysis was also conducted to identify a grouping structure. The results validated all the items of the seven subscales with high values of Cronbach’s alpha (α = 0.732 for D1, α = 0.795 for D2, α = 0.882 for D3, α = 0.742 for D4, α = 0.675 for D5, α = 0.799 for D6 and α = 0.788 for D7). However, by eliminating 17 items, the final values of the alpha increased in all subscales. Factor analysis with extraction by principal component analysis with varimax rotation extracted 14 factors that explained, in total, 65% of the variance, although the first two factors were the most important (35.7% variance explained). In conclusion, the confirmed usefulness of the questionnaire has been hereby validated for assessing consumer perceptions of and knowledge about EI.info:eu-repo/semantics/publishedVersio

Perturbative tests of non-perturbative counting

We observe that a class of quarter-BPS dyons in N=4 theories with charge vector (Q, P) and with nontrivial values of the arithmetic duality invariant I := gcd (Q wedge P) are nonperturbative in one frame but perturbative in another frame. This observation suggests a test of the recently computed nonperturbative partition functions for dyons with nontrivial values of the arithmetic invariant. For all values of I, we show that the nonperturbative counting yields vanishing indexed degeneracy for this class of states everywhere in the moduli space in precise agreement with the perturbative result.Comment: 10 pages, 0 figure

Benzothienoquinolines: new one-pot synthesis and fluorescence studies of their interaction with DNA and polynucleotides

Revised version. "Available online 10 August 2014"In this work, we were able to obtain the benzothieno[3,2-b]quinoline 1 and benzothieno[2,3-c]quinoline 2 using a new one-pot procedure from the reaction of the commercially available 3-bromobenzo[b]thiophene-2-carbaldehyde with 2-aminophenylpinacolborane under Suzuki coupling conditions using a stereochemically hindered ligand, 2-(cyclohexylphosphane)biphenyl and Ba(OH)2.8H2O as the base. Fluorescence properties of the benzothieno[3,2-b]quinoline 1 and the benzothieno[2,3-c]quinoline 2 were studied in solvents of different polarity. Both compounds exhibit a solvent sensitive emission, compound 1 being less fluorescent (quantum yield < 0.05) than compound 2 (quantum yield between 0.04 and 0.10). The interaction of these compounds with salmon sperm DNA and synthetic double-stranded heteropolynucleotides, poly(dA–dT)•(dA–dT) and poly(dG–dC)•(dG–dC), was studied using spectroscopic methods, allowing the determination of the intrinsic binding constants and binding site sizes. The interaction of both compounds is stronger with adenine-thymine (A-T) base pairs. Compound 1 is the most intercalative in salmon sperm DNA (47%) and polynucleotides (46%-49% of intercalated molecules), while for compound 2, 41% is intercalated in salmon sperm DNA and only 8% in poly(dG–dC)•(dG–dC). Docking studies indicate that compound 1 interacts more strongly with DNA than compound 2, with a significant value of binding free energy in the case of intercalation. Minor groove binding is also very favorable and, probably, both mechanisms occur with a preponderance of intercalation in the case of compound 1. Overall, these results indicate that both benzothienoquinolines interact with nucleic acids by both intercalation and groove binding.Foundation for the Science and Technology (FCT, Portugal), for financial support to the Portuguese NMR network (PTNMR) and also to FEDER and QREN for financial support to the Research Centres, CFUM [Strategic Project PEst-C/FIS/UI0607/2013 (FCOMP-01-0124-FEDER-037291)] and CQ/UM [Strategic Project PEst-C/QUI/UI0686/2013 (FCOMP-01-0124-FEDER-037302)], and to the research project PTDC/QUI-QUI/111060/2009 (F-COMP-01-0124-FEDER-015603) also financed by COMPETE/QREN/EU. FCT, POPH-QREN and FSE are acknowledged for the PhD grants of A.R.O.R. (SFRH/BD/90949/2012) and M.S.D.C. (SFRH/BD/47052/2008), for the Post-Doc. Grant of R.C.C. (SFRH/BPD/68344/2010) and for support to MAP-Fis Doctoral Program

Counting all dyons in N =4 string theory

For dyons in heterotic string theory compactified on a six-torus, with electric charge vector Q and magnetic charge vector P, the positive integer I = g.c.d.(Q \wedge P) is an invariant of the U-duality group. We propose the microscopic theory for computing the spectrum of all dyons for all values of I, generalizing earlier results that exist only for the simplest case of I=1. Our derivation uses a combination of arguments from duality, 4d-5d lift, and a careful analysis of fermionic zero modes. The resulting degeneracy agrees with the black hole degeneracy for large charges and with the degeneracy of field-theory dyons for small charges. It naturally satisfies several physical requirements including integrality and duality invariance. As a byproduct, we also derive the microscopic (0,4) superconformal field theory relevant for computing the spectrum of five-dimensional Strominger-Vafa black holes in ALE backgrounds and count the resulting degeneracies

Magnetoliposomes containing calcium ferrite nanoparticles for applications in breast cancer therapy

Magnetoliposomes containing calcium ferrite (CaFe2O4) nanoparticles were developed and characterized for the first time. CaFe2O4 nanoparticles were covered by a lipid bilayer or entrapped in liposomes forming, respectively, solid or aqueous magnetoliposomes as nanocarriers for new antitumor drugs. The magnetic nanoparticles were characterized by UV/Visible absorption, XRD, HR-TEM, and SQUID, exhibiting sizes of 5.2 ± 1.2 nm (from TEM) and a superparamagnetic behavior. The magnetoliposomes were characterized by DLS and TEM. The incorporation of two new potential antitumor drugs (thienopyridine derivatives) specifically active against breast cancer in these nanosystems was investigated by fluorescence emission and anisotropy. Aqueous magnetoliposomes, with hydrodynamic diameters around 130 nm, and solid magnetoliposomes with sizes of ca. 170 nm, interact with biomembranes by fusion and are able to transport the antitumor drugs with generally high encapsulation efficiencies (70%). These fully biocompatible drug-loaded magnetoliposomes can be promising as therapeutic agents in future applications of combined breast cancer therapy.This research was funded by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CF-UM-UP (UID/FIS/04650/2013; UID/FIS/04650/2019), CQUM (UID/QUI/00686/2016; UID/QUI/00686/2019) and LA-26 (PEst-C/SAU/LA0026/2013), and through the research project PTDC/QUI-QFI/28020/2017 (POCI-01-0145-FEDER-028020), financed by FCT, European Fund of Regional Development (FEDER), COMPETE2020 and Portugal2020. The magnetic measurements were supported by projects UTAP-EXPL/NTec/0046/2017, NORTE-01-0145-FEDER-028538 e PTDC/FIS-MAC/29454/2017. The APC was also funded by FCT. B.D.C. acknowledges FCT for a PhD grant (SFRH/BD/141936/2018)

Magnetoliposomes as nanocarriers for fluorescent potential antitumor drugs

Both aqueous magnetoliposomes (AMLs, containing magnetic nanoparticles entrapped in liposomes) and solid magnetoliposomes (SMLs, where clusters of nanoparticles are covered by a lipid bilayer) containing several different nanoparticles (magnetite, nickel ferrite, manganese ferrite or magnesium ferrite) have been developed, exhibiting a superparamagnetic behavior and diameters below 150 nm.Financial support by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding to CF-UM-UP (UID/FIS/04650/2013) and CQUM (UID/QUI/00686/2016) is acknowledged. A.R.O. Rodrigues thanks the FCT for SFRH/BD/90949/2012 PhD grant and funding to MAP-Fis Doctoral Program.info:eu-repo/semantics/publishedVersio

Retrospective analysis of risk factors and gaps in prevention strategies for mother-to-child HIV transmission in Rio de Janeiro, Brazil

Background Despite great progress made in methods to prevent mother-to-child transmission of HIV (MTCT), delivery and uptake of these measures remains a challenge in many countries. Although the Brazilian Ministry of Health aimed to eliminate MTCT by 2015, infection still occured in 15–24% of infants born to HIV-infected mothers. We sought to identify remaining factors that constrain MTCT elimination. Methods We conducted a retrospective, matched case-control study by reviewing hospital charts of infants born to HIV-infected mothers between 1997 and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan area. Cases were defined as HIV-exposed children with two positive HIV tests before 18 months of age; controls were defined as HIV-exposed children with two negative HIV tests before 18 months of age. We performed bivariate and MTCT cascade analyses to identify risk factors for MTCT and gaps in prevention services. Results We included 435 infants and their mothers (145 cases, 290 controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that cases were less likely to complete all individual measures in the antenatal, delivery, and postnatal period (p < 0.05). Assessing completion of the PMTCT cascade, the sequential steps of PMTCT interventions, we found inadequate retention in care among both cases and controls, and cases were significantly less likely than controls to continue receiving care throughout the cascade (p < 0.05). Motives for incompletion of PMTCT measures included infrastructural issues, such as HIV test results not being returned, but were most often due to lack of care-seeking. Over the course of the study period, PMTCT completion improved, although it remained below the 95% target for antenatal care, HIV testing, and antenatal ART set by the WHO. Adding concern, evaluation of co-infections indicated that case infants were also more likely to have congenital syphilis (OR: 4.29; 95% CI: 1.66 to 11.11). Conclusions While PMTCT coverage has improved over the years, completion of services remains insufficient. Along with interventions to promote care-seeking behaviour, increased infrastructural support for PMTCT services is needed to meet the HIV MTCT elimination goal in Brazil as well as address rising national rates of congenital syphilis