Long-range resonant interactions in biological systems

The issue of retarded long-range resonant interactions between two molecules with oscillating dipole moments is reinvestigated within the framework of classical electrodynamics. By taking advantage of a theorem in complex analysis, we present a simple method to work out the frequencies of the normal modes, which are then used to estimate the interaction potential. The main results thus found are in perfect agreement with several outcomes obtained from quantum computations. Moreover, when applied to a biophysical context, our findings shed new light on Fr\"ohlich's theory of selective long-range interactions between biomolecules. In particular, at variance with a long-standing belief, we show that sizable resonant long-range interactions may exist only if the interacting system is out of thermal equilibrium.Comment: Letter : 4 page

Modelação molecular de péptidos bioactivos

Tese de doutoramento em Ciências (ramo de conhecimento em Química)A Angiotensina II é um pequeno péptido, que participa em diversas mecanismos fisiológicos. Com especial interesse para nós, devemos salientar a participação desta hormona no mecanismo de regulação da pressão arterial, estando directamente ligada com o surgimento de algumas patologias como a hipertensão. Uma abordagem ao tratamento da hipertensão é a administração de antagonistas da Angiotensina II, específicas ao seu receptor At1, cuja activação desencadeia uma cascata de respostas fisiológicas que levam ao aumento do valor da pressão arterial. O bloqueio desta activação pelo uso de antagonistas permite controlar os valores da pressão arterial, sem os efeitos secundários que frequentemente surgem com outras abordagens terapêuticas. A inclusão de dialquilglicinas em péptidos, para além de conferir um certo grau de resistência às enzimas digestivas, inclui restrições estruturais que, usadas convenientemente, podem permitir a conservação preferencial de uma estrutura adaptada ao alvo em vista. Neste trabalho, foram realizados estudos estruturais sobre a Angiotensina II e alguns dos seus antagonistas peptídicos, usando simulações moleculares, que permitiram a observação de um conjunto de características estruturais típicas de cada um. Foi igualmente simulado um conjunto de análogos desenhados, procurando encontrar as características estruturais típicas de antagonistas peptídicos da Angiotensina II. Dos compostos simulados, dois foram propostos como bons candidatos a possuírem actividade antagonista. Foi desenvolvida a síntese de análogos de Angiotensina II, usando técnicas clássicas de síntese peptídica em solução. Embora não tenha sido concluída a síntese de nenhum dos candidatos desenhados, as sínteses realizadas permitiram encontrar algumas soluções para problemas de síntese deste tipo de compostos.Angiotensin II is a small peptide, which participates in several physiologic mechanisms. With a special interest to us, we should point out its role on the regulation of blood pressure, being directly involved in the genesis of some pathologies, like hypertension. An approach to the treatment of hypertension is the administration of Angiotensin II antagonists, specific to its At1 receptor, whose activation triggers a cascade of physiologic responses that lead to the increase of blood pressure. The blockage of this activation, using Angiotensin II antagonists, allows the control of blood pressure values, avoiding some side effects common with other therapeutic approaches. The insertion of dialkylglycines on peptides, besides conferring some degree of resistance to the action of digestive enzymes, includes structural restrictions that, properly used, should allow the conservation of a given conformer, specially adapted to the pretended target. In this work, structural studies were performed on Angiotensin II and some of its peptide antagonists, using molecular simulation, which allowed the observation of several structural features that distinguish Angiotensin II and its peptide antagonist. A number of designed analogs were also simulated, searching the structural features identified for Angiotensin II peptide antagonists. From the simulated analogs, two were selected as promising candidates for antagonistic activity. The synthesis of Angiotensin II analogs was developed, using classic techniques of peptide synthesis on solution. Although not completed, the performed synthesis allowed the identification and solution of some problems common to the synthesis of this type of compounds

Phytochemical profile, antioxidant activity and cytotoxicity against keratinocytes, fibroblasts and endothelial cells of picoplanktonic marine cyanobacteria

Combining the increase demand for natural products in skin care formulations, and the bioactive arsenal of cyanobacteria, we aimed with this study to evaluate the potential of a 70% ethanolic extract of picocyanobacteria strains of the genera Cyanobium and Synechocystis for skin care applications.info:eu-repo/semantics/publishedVersio

A natural oxadiazine isolated from cyanobacteria kills cancer cells in multicellular culture systems by impairing cellular respiration

Cyanobacteria are versatile microorganisms that ubiquitously inhabit terrestrial and aquatic ecosystems. They adapt to external threats by mainly producing secondary metabolites. Therefore, cyanobacteria have been recognized as producer of natural products with potential biotechnological applications, such as bioplastics, antifouling, antibiotics, antiprotozoal or anticancer treatment.info:eu-repo/semantics/publishedVersio

Risco de úlceras por pressão e dependência funcional numa unidade de cuidados continuados de longa duração e manutenção

Foi realizado um estudo descritivo, retrospetivo e de natureza quantitativa estudando a população de utentes internados numa Unidade de Cuidados Continuados de Longa Duração e Manutenção (Miranda do Douro) desde a sua abertura até a atualidade* (N=151), com base em três objetivos principais: (1) determinar o perfil sociodemográfico e clínico dos utentes; (2) avaliar os níveis de dependência no momento de admissão e alta; (3) estratificar o risco de desenvolvimento de úlcera por pressão aquando do ingresso na unidade. Os dados foram recolhidos através dos processos dos utentes, tendo em conta uma ficha previamente estruturada com base nas variáveis a incluir no estudo. Quanto aos instrumentos utilizámos a Escala de Braden, para determinar o risco de desenvolver UP e a Escala de Barthel na admissão e alta para avaliar os níveis de dependência funcional. Concluímos que a avaliação do risco de desenvolver UP é uma componente chave da prevenção em cuidados continuados. A avaliação permite identificar utentes mais suscetíveis ao desenvolvimento deste tipo de feridas, e adequar os cuidados às suas necessidades. Ganhos importantes em autonomia foram conseguidos durante o período em análise. Apesar da tipologia de cuidados, patologias incapacitantes associadas, idade avançada, é possível conseguir reabilitar para algumas tarefas básicas e instrumentais de vida diária

Out-of-equilibrium collective oscillation as phonon condensation in a model protein

In the first part of the present paper (theoretical), the activation of out-of-equilibrium collective oscillations of a macromolecule is described as a classical phonon condensation phenomenon. If a macromolecule is modeled as an open system, that is, it is subjected to an external energy supply and is in contact with a thermal bath to dissipate the excess energy, the internal nonlinear couplings among the normal modes make the system undergo a non-equilibrium phase transition when the energy input rate exceeds a threshold value. This transition takes place between a state where the energy is incoherently distributed among the normal modes, to a state where the input energy is channeled into the lowest frequency mode entailing a coherent oscillation of the entire molecule. The model put forward in the present work is derived as the classical counterpart of a quantum model proposed long time ago by H. Fr\"ohlich in the attempt to explain the huge speed of enzymatic reactions. In the second part of the present paper (experimental), we show that such a phenomenon is actually possible. Two different and complementary THz near-field spectroscopic techniques, a plasmonic rectenna, and a micro-wire near-field probe, have been used in two different labs to get rid of artefacts. By considering a aqueous solution of a model protein, the BSA (Bovine Serum Albumin), we found that this protein displays a remarkable absorption feature around 0.314 THz, when driven in a stationary out-of-thermal equilibrium state by means of optical pumping. The experimental outcomes are in very good qualitative agreement with the theory developed in the first part, and in excellent quantitative agreement with a theoretical result allowing to identify the observed spectral feature with a collective oscillation of the entire molecule.Comment: 49 pages, 10 figures; Physical Review X, (2018) in pres

Exploring the bioactive potential of Pisolithus (Basidiomycota): comprehensive insights into antimicrobial, anticancer, and antioxidant properties for innovative applications

Addressing pressing health concerns, modern medical research seeks to identify new antimicrobials to combat drug resistance, novel molecules for cancer treatment, and antioxidants for inflammation-related diseases. Pisolithus (Basidiomycota) is a ubiquitous and widely distributed fungal genus in forest ecosystems, known for establishing ectomycorrhizal associations with a range of host plants, enhancing their growth, and conferring protection against biotic and abiotic stresses. Beyond ecological applications, Pisolithus yields bioactive compounds with medicinal potential. This comprehensive review explores the transversal biological activity of Pisolithus fungi, aiming to provide a thorough overview of their antimicrobial, anticancer, and antioxidant potential. The focus is on elucidating bioactive compounds within Pisolithus to trigger further research for innovative applications. Compounds from Pisolithus displayed antimicrobial activity against a broad spectrum of microorganisms, including antibiotic-resistant bacteria. The efficacy of Pisolithus-derived compounds matched established medications, emphasizing their therapeutic potential. In anticancer research, the triterpene pisosterol stood out with documented cytotoxicity against various cancer cell lines, showcasing promise for novel anticancer therapies. Pisolithus was also recognized as a potential source of antioxidants, with basidiocarps exhibiting high antioxidant activity. In vivo validation and comprehensive studies on a broader range of compounds, together with mechanistic insights into the mode of action of Pisolithus-derived compounds, are compelling areas for future research.info:eu-repo/semantics/publishedVersio

Geometry and stratigraphic relationships of lower Oligocene coral reefs in Lumignano (Berici Hills, northern Italy)

The Cliffs of Lumignano (Northern Italy) are a renowned climbing area, set on the steep walls of lower Oligocene limestones of the Castelgomberto formation which are made mainly of coral boundstone. Lumignano lies approximately on the south-eastern margin of a Cenozoic carbonate platform known as the Lessini Shelf, but the depositional environment of coral reefs is still debated, and it is unclear whether it was a Caribbean-type carbonate platform with a lagoon and steep slope, or a carbonate ramp with coral reefs on the mid ramp. We produced a geological map of the Lumignano area, in which five lithofacies are distinguished and mapped within the Castelgomberto formation. Their spatial distribution and main sedimentological characters outline that landward of coral reefs, a high-energy environment was present and was shallower than the reefs. Seaward of coral reefs, coralline algae and marlstones with bryozoans occur, while no evidence of a slope made of coral rubble was found. Hence, the detailed geological mapping and the documentation of the stratigraphic relationships between lithofacies provided a valuable contribution to the understanding of depositional environments of the lower Oligocene Lessini Shelf. This work also suggests elements for a better definition of the Castelgomberto formation, which could be split in members or lithofacies that can be mapped at a reasonably large scale (1:10000). The coralline algal lithofacies of the Castelgomberto formation is locally indistinguishable from the analogous facies of the underlying Priabona formation, but the boundary between these two units is always marked by an unconformity, which is easy to identify and may be used for the lithostratigraphic definition of the Castelgomberto formation

Análise de um stick de hóquei em patins em remate para futuro desenvolvimento de soluções de reforço estrutural

Do ponto de vista da engenharia, existe pouca informação sobre o hóquei em patins [1], daí ter surgido o interesse pelo estudo do remate deste desporto. O objetivo desta investigação foi criar condições para analisar o comportamento do stick durante um remate de hóquei em patins, recorrendo a técnicas videográficas. Através da análise das imagens obtidas em alta-velocidade, foi possivel obter uma melhor perceção do comportamento do stick em função da força que lhe é aplicada.info:eu-repo/semantics/publishedVersio

Tracing the path between mushrooms and Alzheimer’s Disease—a literature review

Alzheimer’s disease (AD) is well-known among neurodegenerative diseases for the decline of cognitive functions, making overall daily tasks difficult or impossible. The disease prevails as the most common form of dementia and remains without a well-defined etiology. Being considered a disease of multifactorial origin, current targeted treatments have only managed to reduce or control symptoms, and to date, only two drugs are close to being able to halt its progression. For decades, natural compounds produced by living organisms have been at the forefront of research for new therapies. Mushrooms, which are well-known for their nutritional and medicinal properties, have also been studied for their potential use in the treatment of AD. Natural products derived from mushrooms have shown to be beneficial in several AD-related mechanisms, including the inhibition of acetylcholinesterase (AChE) and β-secretase (BACE 1); the prevention of amyloid beta (Aβ) aggregation and neurotoxicity; and the prevention of Tau expression and aggregation, as well as antioxidant and anti-inflammatory potential. Several studies in the literature relate mushrooms to neurodegenerative diseases. However, to the best of our knowledge, there is no publication that summarizes only AD data. In this context, this review aims to link the therapeutic potential of mushrooms to AD by compiling the anti-AD potential of different mushroom extracts or isolated compounds, targeting known AD-related mechanisms.info:eu-repo/semantics/publishedVersio