Molybdenum Induces the expression of a protein containing a new heterometallic Mo-Fe cluster in desulfoVibrio alaskensis

Biochemistry. 2009 Feb 10;48(5):873-82. doi: 10.1021/bi801773t.

NMR assignment of the apo-form of a Desulfovibrio gigas protein containing a novel Mo–Cu cluster

Biomol NMR Assign (2007) 1:81–83 DOI 10.1007/s12104-007-9022-3

A copper protein and a cytochrome bind at the same site on bacterial cytochrome c peroxidase

Biochemistry, 2004, 43 (46), pp 14566–14576 DOI: 10.1021/bi0485833

Structural and functional studies of PpcA: a key protein in the electron transfer pathways of Geobacter sulfurreducens

Dissertação para obtenção do Grau de Doutor em Bioquímica, ramo de Biotecnologia

The Impact of Multifocal Intraocular Lens in Retinal Imaging with Optical Coherence Tomography

Multifocal intraocular lenses (MF IOLs) have concentric optical zones with different dioptric power, enabling patients to have good visual acuity at multiple focal points. However, several optical limitations have been attributed to this particular design. The purpose of this study is to access the effect of MF IOLs design on the accuracy of retinal optical coherence tomography (OCT). Cross-sectional study conducted at the Refractive Surgery Department of Central Lisbon Hospital Center. Twenty-three eyes of 15 patients with a diffractive MF IOL and 27 eyes of 15 patients with an aspheric monofocal IOL were included in this study. All patients underwent OCT macular scans using Heidelberg Spectralis®. Macular thickness and volume values and image quality (Q factor) were compared between the two groups. There were no statistically significant differences between both groups regarding macular thickness or volume measurements. Retinal OCT image quality was significantly lower in the MF IOL group (p < 0.01). MF IOLs are associated with a significant decrease in OCT image quality. However, this fact does not seem to compromise the accuracy of spectral domain OCT retinal measurements.

Bull's Eye Maculopathy in a Patient Treated with Efavirenz

Objective: To report a case of retinal toxicity associated with efavirenz in an adult. Methods: We describe a case of gradual-onset blurry vision in both eyes in a 37-year-old HIV Caucasian woman, on antiretroviral therapy (ART), including efavirenz. Results: The patient presented with a best corrected visual acuity of 20/100 for the right eye (RE) and 20/125 for the left eye (LE). Fundoscopy revealed mottled atrophic changes of the macular retinal pigment epithelium (RPE) in both eyes. Fluorescein angiography revealed an annular pattern of RPE atrophy in both eyes. Full-field electretinography (ERG) was normal. Conclusions: Based on our patient’s history and on previous reports, efavirenz seems to be the culprit in this case. Our report provides evidence in support of routine ophthalmological evaluation of patients on efavirenz.

Rett Syndrome With and Without Detected MECP2 Mutations: an Attempt to Redefine Phenotypes

Background: The diagnosis of Rett syndrome (RTT) is based on a set of clinical criteria, irrespective of mutation status. The aims of this study were (1) to define the clinical differences existing between patients with Rett syndrome with (Group I) and without a MECP2 mutation (Group II), and (2) to characterize the phenotypes associated with the more common MECP2 mutations. Patients and Methods: We analyzed 87 patients fulfilling the clinical criteria for RTT. All were observed and videotaped by the same paediatric neurologist. Seven common mutations were considered separately, and associated clinical features analysed. Results: Comparing Group I and II, we found differences concerning psychomotor development prior to onset, acquisition of propositive manipulation and language, and evolving autistic traits. Based on age at observation, we found differences in eye pointing, microcephaly, growth, number of stereotypies, rigidity, ataxia and ataxic-rigid gait, and severity score. Patients with truncating differed from those with missense mutations regarding acquisition of propositive words and independent gait, before the beginning of the disease, and microcephaly, growth, foot length, dystonia, rigidity and severity score, at the time of observation. Patients with the R168X mutation had a more severe phenotype, whereas those with R133C showed a less severe one. Patients with R294X had a hyperactive behaviour, and those with T158M seemed to be particularly ataxic and rigid. Conclusion: A clear regressive period (with loss of prehension and language, deceleration of growth) and the presence of more than three different stereotypies, rigidity and ataxic-rigid gait seemed to be very helpful in differentiating Group I from Group II.

Adult B-Cell Acute Lymphoblastic Leukemia Cells Display Decreased PTEN Activity and Constitutive Hyperactivation of PI3K/Akt Pathway Despite High PTEN Protein Levels

Adult B-cell acute lymphoblastic leukemia remains a major therapeutic challenge, requiring a better characterization of the molecular determinants underlying disease progression and resistance to treatment. Here, using a phospho-flow cytometry approach we show that adult diagnostic B-cell acute lymphoblastic leukemia specimens display PI3K/Akt pathway hyperactivation, irrespective of their BCR-ABL status and despite paradoxically high basal expression of PTEN, the major negative regulator of the pathway. Protein kinase CK2 is known to phosphorylate PTEN thereby driving PTEN protein stabilization and concomitant PTEN functional inactivation. In agreement, we found that adult B-cell acute lymphoblastic leukemia samples show significantly higher CK2 kinase activity and lower PTEN lipid phosphatase activity than healthy controls. Moreover, the clinical-grade CK2 inhibitor CX-4945 (Silmitasertib) reversed PTEN levels in leukemia cells to those observed in healthy controls, and promoted leukemia cell death without significantly affecting normal bone marrow cells. Our studies indicate that CK2-mediated PTEN posttranslational inactivation, associated with PI3K/Akt pathway hyperactivation, are a common event in adult B-cell acute lymphoblastic leukemia and suggest that CK2 inhibition may constitute a valid, novel therapeutic tool in this malignancy.

Thoracic Duct Decompression for Protein-Losing Enteropathy in Failing Fontan Circulation

An infrequent but devastating late complication of Fontan circulation is protein-losing enteropathy (PLE), which results from unbalanced lymphatic homeostasis. Surgical decompression of the thoracic duct by redirecting its drainage to the pulmonary venous atrium has been introduced recently as a possible treatment. This report describes a single-institution experience with this innovative procedure in 2 patients with failing Fontan circulation with PLE refractory to optimized medical therapy.

Signal transduction pathways involving the hypertension-related WNK1 and WNK4 protein kinases

Dissertação apresentada para obtenção do Grau de Doutor em Biologia, na especialidade de Genética Molecular, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Development and Characterization of bioactive, edible whey protein films and coatings to improve quality and safety of Food products

Dissertação para a obtenção de grau de doutor em Ciências da Engenharia e Tecnologia

Medicago truncatula as a platform for Molecular Farming: a study of the subcellular localization of a human recombinant protein!

Dissertation presented at Faculdade de Ciências e Tecnologia of Universidade Nova de Lisboa to obtain the Degree of Master in Biotecnology

C-reactive protein in early risk assessment in acute pancreatitis

ABSTRACT:C-reactive protein (CRP) has been widely used in the early risk assessment of patients with acute pancreatitis (AP), but unclear aspects about its prognostic accuracy in this setting persist. This project evaluated first CRP prognostic accuracy for severity, pancreatic necrosis (PNec), and in-hospital mortality (IM) in AP in terms of the best timing for CRP measurement and the optimal CRP cutoff points. Secondly it was evaluated the CRP measured at approximately 24 hours after hospital admission (CRP24) prognostic accuracy for IM in AP individually and in a combined model with a recent developed tool for the early risk assessment of patients with AP, the Bedside Index for Severity in AP (BISAP). Two single-centre retrospective cohort studies were held. The first study included 379 patients and the second study included 134 patients. Statistical methods such as the Hosmer-Lemeshow goodness-of-fit test, the area under the receiver-operating characteristic curve, the net reclassification improvement, and the integrated discrimination improvement were used. It was found that CRP measured at approximately 48 hours after hospital admission (CRP48) had a prognostic accuracy for severity, PNec, and IM in AP better than CRP measured at any other timing. It was observed that the optimal CRP48 cutoff points for severity, PNec, and IM in AP varied from 170mg/l to 190mg/l, values greater than the one most often recommended in the literature – 150mg/l. It was found that CRP24 had a good prognostic accuracy for IM in AP and that the cutoff point of 60mg/l had a negative predictive value of 100%. Finally it was observed that the prognostic accuracy of a combined model including BISAP and CRP24 for IM in AP could perform better than the BISAP alone model. These results might have a direct impact on the early risk assessment of patients with AP in the daily clinical practice.--------- RESUMO: A proteina c-reactiva (CRP) tem sido largamente usada na avaliação precoce do risco em doentes com pancreatite aguda (AP), mas aspectos duvidosos acerca do seu valor prognóstico neste contexto persistem. Este projecto avaliou primeiro o valor prognóstico da CRP para a gravidade, a necrose pancreática (PNec) e a mortalidade intra-hospitalar (IM) na AP em termos do melhor momento para efectuar a sua medição e dos seus pontos-de-corte óptimos. Em segundo lugar foi avaliado o valor prognóstico da proteína c-reactiva medida aproximadamente às 24 horas após a admissão hospitalar (CRP24) para a IM na AP isoladamente e num modelo combinado, que incluiu uma ferramenta de avaliação precoce do risco em doentes com AP recentemente desenvolvida, o Bedside Index for Severity in Acute Pancreatitis (BISAP). Dois estudos unicêntricos de coorte retrospectivo foram realizados. O primeiro estudo incluiu 379 doentes e o segundo estudo incluiu 134 doentes. Metodologias estatísticas como o teste de Hosmer-Lemeshow goodness-of-fit, a area under the receiver-operating characteristic curve, o net reclassification improvement e o integrated discrimination improvement foram usadas. Verificou-se que a CRP medida às 48 horas após a admissão hospitalar (CRP48) teve um valor prognóstico para a gravidade, a PNec e a IM na AP melhor do que a CRP medida em qualquer outro momento. Observou-se que os pontos de corte óptimos da CRP48 para a gravidade, a PNec e a IM na AP variaram entre 170mg/l e 190mg/l, valores acima do valor mais frequentemente recomendado na literatura – 150mg/l. Verificou-se que a CRP medida aproximadamente às 24 horas após a admissão hospitalar (CRP24) teve um bom valor prognóstico para a IM na AP e que o ponto de corte 60mg/l teve um valor preditivo negativo de 100%. Finalmente observou-se que o valor prognóstico de um modelo combinado incluindo o BISAP e a CRP24 para a IM na AP pode ter um desempenho melhor do que o do BISAP isoladamente. Estes resultados podem ter um impacto directo na avaliação precoce do risco em doentes com AP na prática clínica diária.

Liver and serum soluble protein changes and pathomorphology in undernourished mice with acute Schistosomiasis mansoni

Body, liver and spleen weights; histopathology of the liver, spleen and intestines; hepatic and serum soluble proteins changes were the parameters studied in undernourished Swiss albino mice experimentally infected with S. mansoni. Non-infected deficient animab had lower liver/body weight and spleen/body weight ratios as compared to the controls (22.60% casein group). Infected mice showed higher values regardless the type of diet. Undernourished infected subgroup showed a persistent exudative periovular reaction in the liver. Soluble hepatic proteins content and serum protein fractions appeared to be lower in the deficient infected mice. A significant difference was detected in the gammaglobulin fraction between infected and non-infected animals fed the control diet with higher values for the former. Our data suggest that the effects of malnutrition, per se, are sometimes more detrimental to the host than those due to Manson 's schistosomiasis.

Structural characterization of the urea-unfolded state of Colicin Immunity Protein Im7 and Im9

Dissertação para obtenção do Grau de Mestre em Bioquímica Estrutural e Funcional