Delayed Diagnosis of Occult Phosphaturic Mesenchymal Tumor in the Foot

Phosphaturic mesenchymal tumors are the main cause of tumor-induced osteomalacia, a distinctive paraneoplastic syndrome mediated by overproduction of fibroblast growth factor 23, that leads to renal phosphate wasting and hypophosphatemia. Diagnosis of this mesenchymal tumors is difficult and usually delayed for several years. We present the case of a 70-years-old-male with generalized bone pain, multiple pathological fractures and persistent hypophosphatemia, diagnosed with tumor-induced osteomalacia after 4 years of the onset of symptoms. The tumor was localized in the forefoot using Gallium 68-DOTANOC positron emission tomography-computed tomography and successfully surgically treated. This case report highlights the importance of recognizing these rare tumors, as early diagnosis can prevent long-term morbidity.info:eu-repo/semantics/publishedVersio

An insight into structure and stability of DNA in ionic liquids from molecular dynamics simulation and experimental studies

Molecular dynamics simulation and biophysical analysis were employed to reveal the characteristics and the influence of ionic liquids (ILs) on the structural properties of DNA. Both computational and experimental evidence indicate that DNA retains its native B-conformation in ILs. Simulation data show that the hydration shells around the DNA phosphate group were the main criteria for DNA stabilization in this ionic media. Stronger hydration shells reduce the binding ability of ILs' cations to the DNA phosphate group, thus destabilizing the DNA. The simulation results also indicated that the DNA structure maintains its duplex conformation when solvated by ILs at different temperatures up to 373.15 K. The result further suggests that the thermal stability of DNA at high temperatures is related to the solvent thermodynamics, especially entropy and enthalpy of water. All the molecular simulation results were consistent with the experimental findings. The understanding of the properties of IL–DNA could be used as a basis for future development of specific ILs for nucleic acid technology

Comparative study of the effect of long-term ageing on the behaviour of bitumen and mastics with mineral fillers

This paper is based on a part of the research project carried out at the request of the German Research Foundation (DFG), under research project No. WE 1642/1-2 and LE 3649/1-2 (FOR2089).This study aims to evaluate the effect of mineral fillers on bitumen ageing. Two different bitumens and four mastics were investigated in the unaged and long-term aged states, based on different properties (consistency, rheology, fatigue resistance and ductility). Mastics stiffened less due to ageing treatment than bitumens, especially with granite filler. However, the results of the performance tests were not definitive regarding the effect of the filler. Aged bitumen showed greater fatigue resistance and higher specific energy of ductile fracture than unaged bitumen, whereas the mastics showed minor variations in the specific energy of ductile fracture with ageing treatment, which is indicative of less ageing, but the fatigue resistance decreased significantly in mastics with one of the bitumens.authorsversionpublishe

Mobility of contaminants in relation to dredging operations in a mesotidal estuary (Tagus Estuary, Portugal)

During the construction of a New Bridge over the Tagus estuary 2.5 million tons of sediments were dredged, part of this quantity being contaminated material. The extension and intensity of the water turbidity associated with dredging operating varied with the tidal conditions but the resuspended material collected near the bucket dredger did not present a concentration increment in metals and PCB, when compared to the estuarine suspended sediments. The calculated distribution coefficients suggest that some contaminants in solids near the dredger were not in equilibrium with the water. A 24-hour laboratory experiment demonstrated the complexity and quickness of anoxic sediments oxidation. In such a short period of time metals in the solids change their fractionation. A second laboratory simulation showed that mussels accumulate metals and PCB congeners when placed in turbid aerated water

Advances in the synthesis of Homochiral (-)-1-azafagomine and (+)-5-epi-1-azafagomine. 1-N-phenyl carboxamide derivatives of both enantiomers of 1-azafagomine: leads for the synthesis of active α-Glycosidase inhibitors

- A new expeditious preparation of homochiral (-)-1-azafagomine, and (+)-5-epi-1-azafagomine has been devised. Stoodley´s diastereoselective cycloaddition of dienes bearing a 2,3,4,6-tetraacetyl glucosyl chiral auxiliary to 4-phenyl-1,2,4-triazole-3,5-dione, was merged with Bols protocol for functionalizing alkenes into molecules bearing a glucosyl framework. Homochiral (+)-5-epi-1-azafagomine was synthetized for the first time. Partial reductive cleavage of the phenyltriazolidinone moiety afforded new homochiral 1-N-phenyl carboxamide derivatives of 1-azafagomine. Both enantiomers of these derivatives were synthetized and tested, displaying a very good enzymatic inhibition towards baker´s yeast α-glucosidase. The molecular recognition mechanism of the 1-N-phenyl carboxamide derivative of 1-azafagomine by α-glucosidase from baker´s yeast was studied by molecular modelling. The efficient packing of the aromatic ring of the 1-N-phenyl carboxamide moiety into a hydrophobic sub-site (pocket) in the enzyme´s active site, seems to be responsible for the improved binding affinity in relation to underivatized (-)1-azafagomine and (+)1-azafagomine.We thank FCT for project funding PTDC/QUI/67407/2006 and FCT and FEDER for funding NMR spectrometer Bruker Avance III 400 as part of the National NMR Network. M.N.M. acknowledges the contract research program "Compromisso com a Ciencia" Reference C2008-UMINHO-CQ-03 and access to the Minho University GRIUM cluster

NMR and molecular modelling studies on elastase inhibitor-peptides for wound management

Proteases play an important and critical role in the physiological process of wound repair. However, excessive and unregulated release of proteolytic enzymes (e.g., elastase) mediates abnormal degradation of healthy tissues, which leads to inflammatory disorders such as chronic wounds. Thus, it is of therapeutic interest to develop novel synthetic inhibitor-peptides of elastase, which can restore the balance between the free enzyme and the endogenous inhibitors in chronic wounds. In previous works, we have reported two different drug delivery systems to release novel elastase inhibitors to the wound site. In both systems synthetic peptides (KRCCPDTCGIKCL-Pep4 and KRMMPDTMGIKML-Pep4M) based on the primary structure of the endogenous elastase inhibitor, secretory leucocyte protease inhibitor, were used as active material. Phosphorylation of the reported peptides prompts significant structural differences, which reflects in distinct inhibitory capacity towards elastase. These structural modifications were prompted by electrostatic interactions and hydrogen bonds established from the peptide phosphoresidue. The current study was also extended to another synthetic peptide (WCTASVPPQCY-PepBBI) that is based on the reactive loop of another elastase inhibitor, the Bowmen-Birk inhibitor. PepBBI, phosphorylated and non-phosphorylated, displays similar behaviour to Pep4 and Pep4M. The structural modifications reported herein were evaluated by two-dimensional nuclear magnetic resonance and molecular modelling approaches.The authors gratefully acknowledge the financial support of the Portuguese Foundation for Science and Technology (scholarship SFRH/BD/36522/2007 and PEst-OE/EQB/LA0004/2011), FEDER (European Fund for Regional Development)-COMPETE-QREN-EU and the European Project Lidwine - Multifunctional medical textiles for wound (e.g. Decubitus). We acknowledge CERMAX at ITQB-UNL and Rede Nacional de RMN for access to the facilities. Rede Nacional de RMN is supported with funds from FCT, Projecto de Re-equipamento Cientifico contract REDE/1517/RMN/2005, Portugal. Micaelo, N.M. acknowledges the contract research program "Compromisso corn a Ciencia" reference: C2008-UMINHO-CQ-03 and access to the Minho University GRIUM cluster

Tailoring cutinase activity towards polyethylene terephthalate and polyamide 6,6 fibers

Cutinase from Fusarium solani pisi was genetically modified near the active site, by site-directed mutagenesis, to enhance its activity towards polyethylene terephthalate (PET) and polyamide 6,6 (PA 6,6) fibers. The mutations L81A, N84A, L182A, V184A and L189A were done to enlarge the active site in order to better fit a larger polymer chain. Modeling studies have shown enhanced free energy stabilization of model substrate tetrahedral intermediate (TI) bound at the enzyme active site for all mutants, for both model polymers. L81A and L182A showed an activity increase of four- and five-fold, respectively, when compared with the wild type, for PET fibers. L182A showed the one- and two-fold higher ability to biodegrade aliphatic polyamide substrates. Further studies in aliphatic polyesters seem to indicate that cutinase has higher ability to recognize aliphatic substrates.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/22490/2005, SFRH/BD/22149/2005European Community - Biosyntex Project, no. G5RD-CT-2000-30110 “Competitive and Sustainable Growth

Influence of anion–water interactions on the behaviour of lipases in room temperature ionic liquids

In this report, molecular dynamics simulations were applied in order to investigate the effect of Room Temperature Ionic Liquid (RTIL) anions toward the structure and dynamic properties of lipases. Two lipases were studied; Candida antarctica lipase B and Candida rugosa lipase were solvated by five RTILs that contained the same cation, with increasing hydration levels. Several properties were investigated: structural deviations and flexibility of the protein conformation, the behaviour of RTILs at the protein surface, and the interactions between RTILs and water molecules in the systems. Both lipases' conformations showed an increased structural stability in RTILs when compared to an aqueous solution. The lowest structural deviation was observed around 15 to 20 percent of water content (w/w protein). The RTIL with the chloride anion was shown to be the exception however, inducing the least structural stability at low water percentages. The flexibility of both lipases was clearly affected when transferred from aqueous into RTILs. The flexible regions found for both lipases in water were significantly more rigid in RTILs. Around the protein surface, the behaviour of RTIL anions and the water molecules was similar to other conventional organic solvents. The water retention ability for all RTIL anions was consistent for both lipases except for the bis(trifluoromethylsulfonyl)imide anion, which showed distinctive behaviour toward different protein surface properties. The effect of water content was more profound compared to the difference between the RTILs anions studied. However, it was found that the structural and dynamic properties of the lipases were affected by the behaviour of anions toward the hydration layer of the enzymes