Contrasting High Scientific Production with Low International Collaboration and Scientific Impact: The Brazilian Case

The article presents an analysis of scientific production and impact among 35 most productive countries in the world. In the period 2000–2016, these countries produced 92% of the world publications. A correlation of international collaboration and scientific impact is shown. Differently from this pattern, Brazil shows high quantitative performance but low scientific impact, which is attributed to its low level of international collaboration. By contrast, instead of a generalized cooperation, as many undeveloped countries do, Brazil uses its internal effort to explore cooperation in a more symmetrical manner. Thus, in several areas, Brazil occupies a prominent position, including technological sectors, enabling it to occupy the eighth world’s economy position. The data confirm that an efficient internal scientific effort combined with well-balanced international cooperation can be more effective to enable countries to achieve higher levels of development in order to meet their technical and socioeconomic challenges. Brazil was able to reach the first step but did not follow the same track concerning higher scientific impact

Lumican Peptides: Rational Design Targeting ALK5/TGFBRI

Lumican, a small leucine rich proteoglycan (SLRP), is a component of extracellular matrix which also functions as a matrikine regulating multiple cell activities. In the cornea, lumican maintains corneal transparency by regulating collagen fibrillogenesis, promoting corneal epithelial wound healing, regulating gene expression and maintaining corneal homeostasis. We have recently shown that a peptide designed from the 13 C-terminal amino acids of lumican (LumC13) binds to ALK5/TGFBR1 (type1 receptor of TGF beta) to promote wound healing. Herein we evaluate the mechanism by which this synthetic C-terminal amphiphilic peptide (LumC13), binds to ALK5. These studies clearly reveal that LumC13-ALK5 form a stable complex. In order to determine the minimal amino acids required for the formation of a stable lumican/ALK5 complex derivatives of LumC13 were designed and their binding to ALK5 investigated in silico. These LumC13 derivatives were tested both in vitro and in vivo to evaluate their ability to promote corneal epithelial cell migration and corneal wound healing, respectively. These validations add to the therapeutic value of LumC13 (Lumikine) and aid its clinical relevance of promoting the healing of corneal epithelium debridement. Moreover, our data validates the efficacy of our computational approach to design active peptides based on interactions of receptor and chemokine/ligand.NIH/NEI grantsResearch to Prevent BlindnessOhio Eye Research FoundationUniv Cincinnati, Dept Ophthalmol, Cincinnati, OH 45267 USAUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, BrazilUniv Houston, Coll Optometry, Ocular Surface Inst, Houston, TX 77204 USAUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, BrazilNIH/NEI grants: RO1 EY011845NIH/NEI grants: R01 021768Web of Scienc

Urinary glycosaminoglycans excretion and the effect of dimethyl sulfoxide in an experimental model of non-bacterial cystitis

PURPOSE: We reproduced a non-bacterial experimental model to assess bladder inflammation and urinary glycosaminoglycans (GAG) excretion and examined the effect of dimethyl sulfoxide (DMSO). MATERIALS AND METHODS: Female rats were instilled with either protamine sulfate (PS groups) or sterile saline (control groups). At different days after the procedure, 24 h urine and bladder samples were obtained. Urinary levels of hyaluronic acid (HA) and sulfated glycosaminoglycans (S-GAG) were determined. Also to evaluate the effect of DMSO animals were instilled with either 50% DMSO or saline 6 hours after PS instillation. To evaluate the effect of DMSO in healthy bladders, rats were instilled with 50% DMSO and controls with saline. RESULTS: In the PS groups, bladder inflammation was observed, with polymorphonuclear cells during the first days and lymphomononuclear in the last days. HA and S-GAG had 2 peaks of urinary excretion, at the 1st and 7th day after PS injection. DMSO significantly reduced bladder inflammation. In contrast, in healthy bladders, DMSO produced mild inflammation and an increase in urinary HA levels after 1 and 7 days and an increase of S-GAG level in 7 days. Animals instilled with PS and treated with DMSO had significantly reduced levels of urinary HA only at the 1st day. Urinary S-GAG/Cr levels were similar in all groups. CONCLUSIONS: Increased urinary levels of GAG were associated with bladder inflammation in a PS-induced cystitis model. DMSO significantly reduced the inflammatory process after urothelial injury. Conversely, this drug provoked mild inflammation in normal mucosa. DMSO treatment was shown to influence urinary HA excretion

Controlo mecânico de infestantes

As infestantes são plantas indesejáveis que crescem juntamente com as plantas cultivadas e que interferem no seu desenvolvimento normal. As infestantes podem ser uma das principais causas da diminuição do rendimento das culturas, porque competem com elas para o espaço, para a água, luz solar, nutrientes e dióxido de carbono, podem segregar substâncias alelopáticas, ser o meio no qual temporariamente se instalam alguns organismos responsáveis por inúmeras pragas e doenças que atacam as culturas dificultando assim o combate às mesmas, dificultam a colheita quer esta seja manual ou mecanizada, podem contaminar o produto final, depreciando-o e, asseguram a reinfestação para as culturas seguintes. O controlo de infestantes ter-se-á iniciado quando o homem deixou a de ser nómada e de assegurar as suas necessidades através da colheita de frutos e da caça e passou após a “domesticação“ das espécies animais e vegetais a fazer agricultura, tornando-se sedentário. Portanto, desde o início da agricultura, que o homem tem feito grandes esforços para controlar as plantas infestantes, primeiro à mão, depois com o uso de alguns artefactos, ferramentas e equipamentos para melhorar a eficiência no seu controlo. Hoje existem equipamentos mecânicos sofisticados tal como, substâncias químicas ou biológicas que permitem o seu controlo prevenindo ou retardando a sua germinação ou crescimento. Interferência das plantas infestantes com a cultura pode gerar perdas significativas, na qualidade e quantidade de alimentos produzidos, desperdiçando enormes quantidades de energia, especialmente não renováveis. Os custos no controlo e os efeitos sobre os rendimentos são muito variáveis, dependendo do agricultor, das espécies de plantas infestantes e da estratégia ou estratégias adoptadas para garantir a eficácia no controlo. Nas últimas cinco décadas têm vindo a fazer-se significativos avanços científicos e tecnológicos na criação de estratégias para o aumento da eficácia no controlo de infestantes seja mecanicamente, seja através da utilização de substâncias químicas ou biológicas menos tóxicas para o homem, menos agressivas ao meio ambiente, com menores custos de produção e ao mesmo tempo, mais selectivas para as culturas onde são aplicadas. A alternativa ao controlo químico de infestantes através da aplicação de herbicidas é o controlo mecânico pela utilização de diversas alfaias agrícolas, tais como a charrua de aivecas, a charrua de discos, o escarificador de braços rígidos, o escarificador de braços flexíveis (vibrocultor) e a fresa. O controlo mecânico de infestantes poderá ser levado a cabo também por máquinas de corte, como por exemplo, as gadanheiras. Cortar as infestantes numa fase de desenvolvimento antes da produção de semente evita a sua propagação. Se o agricultor optar pela sementeira directa como técnica de instalação das culturas, a única alternativa que tem para o controlo de infestantes é a química, mas se optar pelo sistema de mobilização tradicional ou pela mobilização reduzida poderá controlar as infestantes, química e/ou mecanicamente. A eficácia das diferentes alfaias no controlo de infestantes depende da própria alfaia, da época do ano em que se realiza esse controlo, do estado do solo, das espécies de infestantes presentes e seu estádio de desenvolvimento. Iremos no presente trabalho, referir os aspectos mais importantes do controlo mecânico de infestantes

Antithrombin stabilisation by sulfated carbohydrates correlates with anticoagulant activity

Thermal stabilisation of native antithrombin-III (AT), determined using differential scanning fluorimetry, correlated with the anticoagulant activity of heparin and heparin-related saccharides. Similar conformational changes were induced in native AT by a variety of active and inactive heparin-related sulfated carbohydrates, measured in solution using synchrotron radiation circular dichroism, and their anticoagulant activities. Measurement of native AT stabilisation provides a convenient assay for prospective anticoagulants and represents an additional parameter by which to compare biosimilar heparins.National Science Foundation's National High Magnetic Field Laboratory User Program in the Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) Facility (McKnight Brain Institute, University of Florida, USA)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo UNIFESP, Dept Biochem, BR-04044020 São Paulo, BrazilDiamond Light Source Ltd, Beam Line Circular Dichroism 23, Didcot OX11 ODE, Oxon, EnglandUniv Liverpool, Dept Struct & Chem Biol, Liverpool L69 7ZB, Merseyside, EnglandIst Ric Chim & Biochim G Ronzoni, I-20133 Milan, ItalyUniv Fed Rio Grande do Norte, Dept Biochem, BR-59072970 Natal, RN, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Biochem, BR-04044020 São Paulo, BrazilWeb of Scienc

Evaluation of the metabolism of glycosaminoglycans in patients with interstitial cystis

ABSTRACT ARTICLE INFO ______________________________________________________________ ______________________ Introduction: Painful bladder syndrome/interstitial cystitis (PBS/IC) pathogenesis is not fully known, but evidence shows that glycosaminoglycans (GAG) of bladder urothelium can participate in its genesis. The loss of these compounds facilitates the contact of urine compounds with deeper portions of bladder wall triggering an inflammatory process. We investigated GAG in urine and tissue of PBS/IC and pure stress urinary incontinence (SUI) patients to better understand its metabolism. Materials and Methods: Tissue and urine of 11 patients with PBS/IC according to NIDDK criteria were compared to 11 SUI patients. Tissue samples were analyzed by histological, immunohistochemistry and immunofluorescence methods. Statistical analysis were performed using t Student test and Anova, considering significant when p < 0.05. Results: PBS/IC patients had lower concentration of GAG in urine when compared to SUI (respectively 0.45 ± 0.11 x 0.62 ± 0.13 mg/mg creatinine, p < 0.05). However, there was no reduction of the content of GAG in the urothelium of both groups. Immunofluorescence showed that PBS/IC patients had a stronger staining of TGF-beta, decorin (a proteoglycan of chondroitin/dermatan sulfate), fibronectin and hyaluronic acid. Conclusion: the results suggest that GAG may be related to the ongoing process of inflammation and remodeling of the dysfunctional urothelium that is present in the PBS/IC

Clinical and laboratorial study of 19 cases of mucopolysaccharidoses

The mucopolysaccharidoses (MPS) are a heterogeneous group of inborn errors of lysosomal glycosaminoglycan (GAG) metabolism. The importance of this group of disorders among the inborn errors of metabolism led us to report 19 cases. METHOD: We performed clinical, radiological, and biochemical evaluations of the suspected patients, which allowed us to establish a definite diagnosis in 19 cases. RESULTS: Not all patients showed increased GAG levels in urine; enzyme assays should be performed in all cases with strong clinical suspicion. The diagnosis was made on average at the age of 48 months, and the 19 MPS cases, after a full clinical, radiological, and biochemical study, were classified as follows: Hurler -- MPS I (1 case); Hunter -- MPS II (2 cases); Sanfilippo -- MPS III (2 cases); Morquio -- MPS IV (4 cases); Maroteaux-Lamy -- MPS VI (9 cases); and Sly -- MPS VII (1 case). DISCUSSION: The high relative frequency of Maroteaux-Lamy disease contrasts with most reports in the literature and could express a population variability.As mucopolissacaridoses (MPS) constituem um grupo de erros inatos do metabolismo lisossomal dos glicosaminoglicanos (GAG) bastante heterogêneo. A importância das MPS levou-nos a relatar as características de 19 casos. MÉTODO: Realizamos uma avaliação clínica, radiológica e bioquímica, incluindo estudos enzimáticos, que nos permitiram estabelecer o diagnóstico definitivo em 19 casos. RESULTADOS: Nem todos os pacientes apresentaram níveis elevados de GAG na urina, devendo os ensaios enzimáticos serem realizados em todos os pacientes com forte suspeita clínica. O diagnóstico foi estabelecido em média aos 48 meses de idade e os casos, após amplo estudo clínico, radiológico e bioquímico, foram classificados como: Hurler -- MPS I (1 caso); Hunter -- MPS II (2 casos); Sanfilippo -- MPS III (2 casos); Morquio -- MPS IV (4 casos); Maroteaux-Lamy -- MPS VI (9 casos); e Sly -- MPS VI (1 caso). DISCUSSÃO: A proporção relativamente alta de MPS VI (Maroteaux-Lamy) contrasta com a maioria dos dados da literatura e pode expressar uma variabilidade populacional

Heparan sulfate and heparin interactions with proteins.

Heparan sulfate (HS) polysaccharides are ubiquitous components of the cell surface and extracellular matrix of all multicellular animals, whereas heparin is present within mast cells and can be viewed as a more sulfated, tissuespecific, HS variant. HS and heparin regulate biological processes through interactions with a large repertoire of proteins. Owing to these interactions and diverse effects observed during in vitro, ex vivo and in vivo experiments, manifold biological/pharmacological activities have been attributed to them. The properties that have been thought to bestow protein binding and biological activity upon HS and heparin vary from high levels of sequence specificity to a dependence on charge. In contrast to these opposing opinions, we will argue that the evidence supports both a level of redundancy and a degree of selectivity in the structure–activity relationship. The relationship between this apparent redundancy, the multi-dentate nature of heparin and HS polysaccharide chains, their involvement in protein networks and the multiple binding sites on proteins, each possessing different properties, will also be considered. Finally, the role of cations in modulating HS/heparin activity will be reviewed and some of the implications for structure–activity relationships and regulation will be discussed

High-sensitivity visualisation of contaminants in heparin samples by spectral filtering of H-1 NMR spectra

A novel application of two-dimensional correlation analysis has been employed to filter H-1 NMR heparin spectra distinguishing acceptable natural variation and the presence of foreign species. Analysis of contaminated heparin samples, compared to a dataset of accepted heparin samples using two-dimensional correlation spectroscopic analysis of their 1-dimensional H-1 NMR spectra, allowed the spectral features of contaminants to be recovered with high sensitivity, without having to resort to more complicated NMR experiments. Contaminants, which exhibited features distinct from those of heparin and those with features normally hidden within the spectral mass of heparin could be distinguished readily. A heparin sample which had been pre-mixed with a known contaminant, oversulfated chondroitin sulfate (OSCS), was tested against the heparin reference library. It was possible to recover the 1 H NMR spectrum of the OSCS component through difference 2D-COS power spectrum analysis of as little as 0.25% (w/w) with ease, and of 2% (w/w) for more challenging contaminants, whose NMR signals fell under those of heparin. the approach shows great promise for the quality control of heparin and provides the basis for greatly improved regulatory control for the analysis of heparin, as well as other intrinsically heterogeneous and varied products.Wellcome TrustRoyal SocietyBBSRCFinlambardia SPA 'Fondo per la promozione di Accordi Istituzionali'Univ Liverpool, Sch Biol Sci, Liverpool L69 3BX, Merseyside, EnglandIst Ric Chim & Biochim G Ronzoni, I-20133 Milan, ItalyUNIFESP Universidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, BR-04044020 São Paulo, BrazilKeele Univ, Inst Sci & Technol Med, Keele ST5 5BG, Staffs, EnglandNatl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, EnglandUNIFESP Universidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, BR-04044020 São Paulo, BrazilWeb of Scienc