Synthesis of b-substituted alanines via Michael addition of nucleophiles to dehydroalanine derivatives

Several b-substituted alanines are synthesised in high yields by a Michael addition of nucleophiles to N-acyl,N-tert-butyloxycarbonyl-dehydroalanine methyl ester, using mild reaction conditions and simple work-up procedures. The same method can be applied to dipeptides containing dehydroalanine

Michael addition of thiols, carbon nucleophiles and amines to dehydroamino acid and dehydropeptide derivatives

Michael additions of nitrogen heterocycles, thiols, carbon nucleophiles and amines to dehydroalanine derivatives, including a glycyldehydroalanine peptide, were performed in fair to good yields. Dehydroaminobutyric acid derivatives reacted only with the stronger nucleophiles but in considerably lower yields and often no reaction was observed with the corresponding dehydrophenylalanine derivatives. When a tosyl group was bonded to the nitrogen atom of the dehydroamino acid, in some cases the addition product underwent elimination of this group and yielded the corresponding b-substituted derivative of the a,b-dehydroamino acid. Addition of some b- dicarbonyl compounds led to formation of products to which the structure of a,a-disubstituted cyclic amino acid derivatives was assigned

High yielding synthesis of dehydroamino acid and dehydropeptide derivatives

By using a dimethylaminopyridine (DMAP) catalysed reaction of b-hydroxyamino acid derivatives with tert-butylpyrocarbonate [(Boc)2O], dehydroamino acid derivatives are obtained in high yields. The same methodology applied to dipeptides with a b-hydroxyamino acid residue gives the corresponding dipeptides with a dehydroamino acid residue

Clarifying changes in student empathy throughout medical school: a scoping review

Despite the increasing awareness of the relevance of empathy in patient care, some findings suggest that medical schools may be contributing to the deterioration of students' empathy. Therefore, it is important to clarify the magnitude and direction of changes in empathy during medical school. We employed a scoping review to elucidate trends in students' empathy changes/differences throughout medical school and examine potential bias associated with research design. The literature published in English, Spanish, Portuguese and French from 2009 to 2016 was searched. Two-hundred and nine potentially relevant citations were identified. Twenty articles met the inclusion criteria. Effect sizes of empathy scores variations were calculated to assess the practical significance of results. Our results demonstrate that scoped studies differed considerably in their design, measures used, sample sizes and results. Most studies (12 out of 20 studies) reported either positive or non-statistically significant changes/differences in empathy regardless of the measure used. The predominant trend in cross-sectional studies (ten out of 13 studies) was of significantly higher empathy scores in later years or of similar empathy scores across years, while most longitudinal studies presented either mixed-results or empathy declines. There was not a generalized international trend in changes in students' empathy throughout medical school. Although statistically significant changes/differences were detected in 13 out of 20 studies, the calculated effect sizes were small in all but two studies, suggesting little practical significance. At the present moment, the literature does not offer clear conclusions relative to changes in student empathy throughout medical school.info:eu-repo/semantics/publishedVersio

Virulence factors of non-Candida albicans Candida species

Infections caused by Candida species (candidosis) have greatly increased over recent years, mainly due to the escalation of the AIDS epidemic, population ageing, increasing number of immunocompromised patients and the more widespread use of indwelling medical devices. Besides Candida albicans, non-Candida albicans Candida (NCAC) species such as Candida glabrata, Candida tropicalis and Candida parapsilosis are now frequently identified as potential human pathogens. Candida species pathogenicity is facilitated by a number of virulence factors, most importantly adherence to medical devices and/or host cells, biofilm formation, and secretion of enzymes, such as proteases. Thus, we have been studying several of the most relevant virulence factors (adhesion, biofilm formation ability, tissue colonisation and invasion, expression of hydrolytic enzymes and antifungal agents susceptibility) of Candida clinical isolates recovered from different body sites (oral cavity and urinary and vaginal tracts). In summary, this presentation underlines both species and strain differences in terms of virulence factors associated with C. glabrata, C. parapsilosis and C. tropicalis. Furthermore, there is clear evidence demonstrating the importance of the use of new techniques including Confocal Laser Scanning Microscopy and molecular analysis tools enabling the elucidation of the mechanisms of virulence. By increasing our knowledge on Candida pathogenesis, new potential therapeutic targets may be identified that can be used as adjuvants for novel therapies

A modular reactor to simulate biofilm development in orthopedic materials

Surfaces of medical implants are generally designed to encourage soft- and/or hard-tissue adherence, eventually leading to tissue- or osseo-integration. Unfortunately, this feature may also encourage bacterial adhesion and biofilm formation. To understand the mechanisms of bone tissue infection associated with contaminated biomaterials, a detailed understanding of bacterial adhesion and subsequent biofilm formation on biomaterial surfaces is needed. In this study, a continuous-flow modular reactor composed of several modular units placed in parallel was designed to evaluate the activity of circulating bacterial suspensions and thus their predilection for biofilm formation during 72 h of incubation. Hydroxyapatite discs were placed in each modular unit and then removed at fixed times to quantify biofilm accumulation. Biofilm formation on each replicate of material, unchanged in structure, morphology, or cell density, was reproducibly observed. The modular reactor therefore proved to be a useful tool for following mature biofilm formation on different surfaces and under conditions similar to those prevailing near human-bone implants. [Int Microbiol 2013; 16(3):191-198]Keywords: orthopedic materials · orthopedic conditions · modular reactors · continuous flow · biomaterials · biofilm formatio

Contributo para o conhecimento da biodiversidade marinha da ilha das Flores

XIII Expedição Científica do Departamento de Biologia - Flores e Corvo 2007.No âmbito da XIII Expedição Científica Flores e Corvo/2007, organizada pelo Departamento de Biologia da Universidade dos Açores, efectuaram-se várias observações e recolhas de organismos marinhos, utilizando 3 metodologias: mergulho (bentos), arrasto (plâncton) e prospecção no intertidal

Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea

Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes

A review on the laser-assisted flow deposition method: growth of ZnO micro and nanostructures

Zinc oxide (ZnO) is a widely versatile semiconductor with major importance from the technological point of view, presenting the advantage to be grown by a large number of techniques and with one of the richest varieties of morphologies. Due to the special interest of this semiconductor, several methods have been developed to control the production of its nanostructures. Herein, we report the development of a vapour-based method, designated by laser-assisted flow deposition (LAFD), able of producing ZnO micro and nanocrystals with different morphologies, with a high crystalline and optical quality. This new process allows high yield of ZnO production, showing great prospects for scalable applications. In the present work, we review in detail the main growth parameters and their relationship with the produced morphologies, in addition to their influence in the structural and optical properties. Furthermore, an assessment of the possible growth mechanisms that may be involved in this new method is reported. Some potential applications of the ZnO structures produced by LAFD were also evaluated, with focus on the photocatalysis and photovoltaic fields. Additionally, the possibility of synthesizing ZnO composite nanostructures, as well as the growth of other metal oxides using this technique was explored.publishe

Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer

BACKGROUND. Monocarboxylate transporters (MCTs) are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, however the role of MCTs in prostate cancer is largely unknown.The aim of the present work was to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs) expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1/4 and MCT2 chaperones, respectively, in prostate carcinoma. METHODS. Prostate tissues were obtained from 171 patients, who performed radical prostatectomy and 14 patients who performed cystoprostatectomy. Samples and clinico-pathological data were retrieved and organized into tissue microarray (TMAs) blocks. Protein expression was evaluated by immunohistochemistry in neoplastic (n= 171), adjacent non-neoplastic tissues (n= 135), PIN lesions (n=40) and normal prostatic tissue (n=14). Protein expression was correlated with patients' clinicopathologic characteristics. RESULTS. In the present study, a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. All MCT isoforms and CD147 were expressed in PIN lesions. Importantly, for MCT2 and MCT4 the expression levels in PIN lesions were between normal and tumour tissue, which might indicate a role for these MCTs in the malignant transformation. Associations were found between MCT1, MCT4 and CD147 expressions and poor prognosis markers; importantly MCT4 and CD147 overexpression correlated with higher PSA levels, Gleason score and pT stage, as well as with perineural invasion and biochemical recurrence. CONCLUSIONS. Our data provides novel evidence for the involvement of MCTs in prostate cancer. According to our results, we consider that MCT2 should be further explored as tumour marker and both MCT4 and CD147 as markers of poor prognosis in prostate cancer.NPG, CP and VMG received fellowships from the Portuguese Foundation for Science and Technology (FCT), refs. SFRH/BD/61027/2009, SFRH/BPD/69479/ 2010 and SFRH/BI/33503/2008, respectively. This work was supported by the FCT grant ref. PTDC/SAU-FCF/104347/2008, under the scope of Programa Operacional Temático Factores de Competitividade” (COMPETE) of Quadro Comunitário de Apoio III and co-financed by Fundo Comunitário Europeu FEDER