Photolabile protection for amino acids: studies on the release from novel benzoquinolone cages

The synthesis of a novel fused nitrogen heterocycle, benzoquinolone, for evaluation as a photocleavable protecting group is described for the first time, by coupling to model amino acids (alanine, phenylalanine and glutamic acid). Conversion of the phenylalanine ester conjugate to the thionated derivative was accomplished by reaction with Lawesson’s reagent. Photocleavage studies of the carbonyl and thiocarbonyl benzoquinolone conjugates in various solvents and at different wavelengths (300, 350 and 419 nm) showed that the most interesting result was obtained at 419 nm for the thioconjugate, revealing that the presence of the thiocarbonyl group clearly improved the photolysis rates, giving practicable irradiations times for the release of the amino acids (less than 1 minute).

Towards high performance and multi-functional structural membranes using advanced fibrous and textile materials

Scientific and technological advancements in the area of fibrous and textile materials have greatly enhanced their application potential in several high-end technical and industrial sectors including construction, transportation, medical, sports, aerospace engineering, electronics and so on. Excellent performance accompanied by light-weight, mechanical flexibility, tailor-ability, design flexibility, easy fabrication and relatively lower cost are the driving forces towards wide applications of these materials. Cost-effective fabrication of various advanced and functional materials for structural parts, medical devices, sensors, energy harvesting devices, capacitors, batteries, and many others has been possible using fibrous and textile materials. Structural membranes are one of the innovative applications of textile structures and these novel building skins are becoming very popular due to flexible design aesthetics, durability, lightweight and cost benefits. Current demand on high performance and multi-functional materials in structural applications has motivated to go beyond the basic textile structures used for structural membranes and to use innovative textile materials. Structural membranes with self-cleaning, thermoregulation and energy harvesting capability (using solar cells) are examples of such recently developed multi-functional membranes. Besides these, there exist enormous opportunities to develop wide varieties of multi-functional membranes using functional textile materials. Additionally, it is also possible to further enhance the performance and functionalities of structural membranes using advanced fibrous architectures such as 2D, 3D, hybrid, multi-layer and so on. In this context, the present paper gives an overview of various advanced and functional fibrous and textile materials which have enormous application potential in structural membranes.

Polyphasic identification of a Rhizopus species and a putative novel Gongronella which both degrade the fungicide metalaxyl

Apresentação efetuada na MicroBiotec’15

A novel and efficient approach to new N3-substituted-6,8-diaminopurines

[Excerpt] Purine nucleobases are fundamental biochemicals in living organisms. They have been a valuable inspiration for drug design once they play several key roles in the cell.1 To the best of our knowledge, reported routes to 8-aminopurines are still scarce due to the difficulty in introducing amino groups in this position of the purine ring. Here we report a novel, inexpensive and facile synthetic method to generate N3,N6-disubstituted-6,8-diaminopurines. In our research group, a number of substituted purines have been obtained from a common imidazole precursor, the 5-amino-4-cyanoformimidoyl imidazole 1. Recently, a comprehensive study on the reactivity of imidazoles 1 with nucleophiles under acidic conditions led us to develop experimental methods to incorporate primary amines into the cyanoformimidoyl group.2 (...)

The synthesis of novel 5-aminoimidazoles derivatives with anticancer activity

[Excerpt] The imidazole nucleus is present in a significant number of biomolecules and the inclusion of this moiety in organic scaffolds is considered an important synthetic strategy in drug discovery.[1] 5-Aminoimidazoles are interesting building blocks in medicinal chemistry since they are key components in many bioactive molecules and their derivatives showed a wide pharmacological potential as anticancer drugs.[1] The hydrazones constitute an important class of biological active drug molecules due to their wide range of pharmacological properties that include antitumoral activities.[2] Amidrazone derivatives could be considered very promising in the perspective of new drug discovery, because they are very effective as building blocks to obtain various heterocycles.[2,3] The α-hydrazononitriles are a special case of compounds belonging to the family of hydrazones that is less common in the literature, but has a great interest due to their pharmacological applications.[4] (...)

Myopia control with a novel peripheral gradient soft lens and orthokeratology: a 2-year clinical trial

Objective. To evaluate the degree of axial elongation with soft radial refractive gradient (SRRG) contact lenses, orthokeratology (OK), and single vision (SV) spectacle lenses (control) during a period of 1 year before treatment and 2 years after treatment. Methods. This was a prospective, longitudinal, nonrandomized study. The study groups consisted of 30, 29, and 41 children, respectively. The axial length (AL) was measured during 2 years after recruitment and lens fitting. Results. The baseline refractive sphere was correlated significantly (r 2 = 0.542; P < 0.0001) with the amount of myopia progression before baseline. After 2 years, the mean myopia progression values for the SRRG, OK, and SV groups were −0.56 ± 0.51, −0.32 ± 0.53, and −0.98 ± 0.58 diopter, respectively. The results represent reductions in myopic progression of 43% and 67% for the SRRG and OK groups, respectively, compared to the SV group. The AL increased more in the SV group compared to the SRRG and OK groups, with 27% and 38% lower axial elongation, respectively, compared to the SV group at the 2-year visit (P < 0.05). SRRG and OK showed no differences (P = 0.430). Conclusion. The SRRG lens significantly decreased AL elongation compared to the SV control group. The SRRG lens was similarly effective to OK in preventing myopia progression in myopic children and adolescent.

Transcranial direct current stimulation based metaplasticity protocols in working memory

It has been already shown that delivering tDCS that are spaced by an interval alters its impact on motor plasticity. These effects can be explained, based on metaplasticity in which a previous modification of activity in a neuronal network can change the effects of subsequent interventions in the same network. But to date there is limited data assessing metaplasticity effects in cognitive functioning.

Novel auxetic structures from basalt braided composites for structural applications

Auxetic materials are a class of materials behaves unusual way compared to regular materials i.e. possess negative Poisson’s ratio. This paper reports, the development of auxetic structures based on re-entrant hexagon design from braided composite materials and testing of the mechanical properties (tensile property, auxetic property and work of rupture). The structure developed from glass and basalt braided composite rods and properties were compared between them. Later, the basic re-entrant hexagon design was modified with vertical straight rods to improve their mechanical behavior and their auxetic property was studied. Auxetic behavior of these structures was studied in a tensile testing machine taking video during testing by Digital camera, later the video converted into images to measure the strain values using simple software, ImageJ. Along with experimental work, analytical model was used to calculate the Poisson’s ratio of basic structure and results were compared

Search for flavour-changing neutral current top quark decays t → Hq in pp collisions at √s=8 TeV with the ATLAS detector

A search for flavour-changing neutral current decays of a top quark to an uptype quark (q = u, c) and the Standard Model Higgs boson, where the Higgs boson decays to bb¯¯, is presented. The analysis searches for top quark pair events in which one top quark decays to Wb, with the W boson decaying leptonically, and the other top quark decays to Hq. The search is based on pp collisions at s√=8 TeV recorded in 2012 with the ATLAS detector at the CERN Large Hadron Collider and uses an integrated luminosity of 20.3 fb−1. Data are analysed in the lepton-plus-jets final state, characterised by an isolated electron or muon and at least four jets. The search exploits the high multiplicity of b-quark jets characteristic of signal events, and employs a likelihood discriminant that uses the kinematic differences between the signal and the background, which is dominated by tt¯→WbWb decays. No significant excess of events above the background expectation is found, and observed (expected) 95% CL upper limits of 0.56% (0.42%) and 0.61% (0.64%) are derived for the t → Hc and t → Hu branching ratios respectively. The combination of this search with other ATLAS searches in the H → γγ and H → WW *, ττ decay modes significantly improves the sensitivity, yielding observed (expected) 95% CL upper limits on the t → Hc and t → Hu branching ratios of 0.46% (0.25%) and 0.45% (0.29%) respectively. The corresponding combined observed (expected) upper limits on the |λ tcH | and |λ tuH | couplings are 0.13 (0.10) and 0.13 (0.10) respectively. These are the most restrictive direct bounds on tqH interactions measured so far.

Systems biology approaches for the design of novel Saccharomyces cerevisiae winemaking strains for enhanced flavour compounds synthesis

Tese de Doutoramento em Biologia Ambiental e Molecular

Current and previous eating practices among women recovered from anorexia nervosa: a qualitative approach

OBJECTIVE: The aim of this study was to analyze qualitatively how women, who have recovered from anorexia nervosa, perceive and describe their current eating practices, as well as the ones developed during the eating disorder period. METHODS: Seven women were interviewed individually with the objective of investigating their eating practices, transition phases and all relevant aspects that somewhat contributed to the habit-forming; experiences, feelings and perceptions related to mealtime and the influence that food has had over the present subjects' life. The interviews were analyzed by the discourse of the collective subject method. RESULTS: The results brought up the following topics: a) control; b) concerns and feelings; c) deprivation d) beauty dictatorship; e) eating competence; f) importance of food; g) food cacophony. CONCLUSIONS: What stands out is a multiplicity of eating practices, which during the eating disorder were similar to and characterized by restriction; however, after recovery, part of the subjects seem to have developed a higher eating competence, whereas others show a practice similar to the one acquired during the anorexia nervosa, such as the difficulty in realizing when they are satisfied and a feeling of discomfort when facing social interactions.

Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication

Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of three genes-SMYD2, SETD3, and NO66-was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity (AUC=0.959), and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC: 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness.

Development of Janus hydrogel microcapsules as novel biomaterials-stem cells construct for 3D co-culture applications

Co-cultures of two or more cell types and biodegradable biomaterials of natural origin have been successfully combined to recreate tissue microenvironments. Segregated co-cultures are preferred over conventional mixed ones in order to better control the degree of homotypic and heterotypic interactions. Hydrogel-based systems in particular, have gained much attention to mimic tissue-specific microenvironments and they can be microengineered by innovative bottom-up approaches such as microfluidics. In this study, we developed bi-compartmentalized (Janus) hydrogel microcapsules of methacrylated hyaluronic acid (MeHA)/methacrylated-chitosan (MeCht) blended with marine-origin collagen by droplet-based microfluidics co-flow. Human adipose stem cells (hASCs) and microvascular endothelial cells (hMVECs) were co-encapsulated to create platforms of study relevant for vascularized bone tissue engineering. A specially designed Janus-droplet generator chip was used to fabricate the microcapsules (<250â μm units) and Janus-gradient co-cultures of hASCs: hMVECs were generated in various ratios (90:10; 75:25; 50:50; 25:75; 10:90), through an automated microfluidic flow controller (Elveflow microfluidics system). Such monodisperse 3D co-culture systems were optimized regarding cell number and culture media specific for concomitant maintenance of both phenotypes to establish effective cell-cell (homotypic and heterotypic) and cell-materials interactions. Cellular parameters such as viability, matrix deposition, mineralization and hMVECs re-organization in tube-like structures, were enhanced by blending MeHA/MeCht with marine-origin collagen and increasing hASCs: hMVECs co-culture gradient had significant impact on it. Such Janus hybrid hydrogel microcapsules can be used as a platform to investigate biomaterials interactions with distinct combined cell populations.

A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening

We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.

Current Challenges in Modeling Cellular Metabolism

Mathematical and computational models play an essential role in understanding the cellular metabolism. They are used as platforms to integrate current knowledge on a biological system and to systematically test and predict the effect of manipulations to such systems. The recent advances in genome sequencing techniques have facilitated the reconstruction of genome-scale metabolic networks for a wide variety of organisms from microbes to human cells. These models have been successfully used in multiple biotechnological applications. Despite these advancements, modeling cellular metabolism still presents many challenges. The aim of this Research Topic is not only to expose and consolidate the state-of-the-art in metabolic modeling approaches, but also to push this frontier beyond the current edge through the introduction of innovative solutions. The articles presented in this e-book address some of the main challenges in the field, including the integration of different modeling formalisms, the integration of heterogeneous data sources into metabolic models, explicit representation of other biological processes during phenotype simulation, and standardization efforts in the representation of metabolic models and simulation results.