1,721,000 research outputs found
Dynamical properties of myoglobin in an ultraviscous water-glycerol solvent investigated with elastic neutron scattering and FTIR spectroscopy
Full text linkProteins have distinctive dynamical properties, characterized by the fluctuations of protein molecules among the different minima of their energy landscape. These fluctuations, progressively activated for temperature values larger than ~180 K, lead to a steep increase in the temperature dependence of all measurable dynamical properties. This phenomenon is known as Protein Dynamical Transition and, in spite of the intense studies due to its importance in protein function and to the relation with the fascinating fundamental thermodynamics of complex systems, many aspects of it are not yet clearly understood. Among these, the relationship with the properties of the external solvent and the molecular details of the involved protein motions still need further investigations. We report here a comparative study of the Dynamical Transition in a Protein-Glycerol-Water system, from two different points of view: i) Elastic Neutron Scattering (ENS), which gives the Mean Square Displacements of the hydrogen atoms of the protein and is particularly sensitive to side chain motions; ii) Fourier Transform Infrared Spectroscopy (FTIR) in the Amide regions, which is sensitive mainly to the properties of the backbone atoms of the protein. The obtained results show an almost superimposable thermal behavior of protein backbone (FTIR data) and side chains (ENS data). Thus, in our experimental conditions, the Protein Dynamical Transition emerges as a unique thermodynamic process related to the properties of the external Glycerol/Water medium and implying a general softening of the whole protein molecule (backbone and side chains), which is a prerequisite for protein function
Casein-loaded proteoliposomes: Drug Delivery Systems and Potential Inhibitors in Aβ1-40 Fibrillogenesis
No full textAlzheimer's disease (AD) represents the most common cause of dementia worldwide. The early symptom is usually a short-term memory loss, followed by symptoms including problems with language, disorientation, mood swings, loss of motivation, not managing self-care, and behavioral issues, until loss of body functions and, ultimately, death. The cause of AD is poorly understood and the diagnosis is complex. One of the main AD hallmarks is the extracellular deposition in brain tissue of proteinaceous amyloid plaques, composed by well-ordered fibrillary aggregates of the amyloid β-peptide (Aβ). The Aβ aggregation process follows typical nucleation-polymerization kinetics, characterized by structural intermediates with relevant cytotoxic activity. Such smaller soluble Aβ prefibrillar oligomers result indeed the most toxic species, able to interact with membranes by interfering with the cell function. Therefore, novel therapeutic strategies target oligomers or prefibrillar aggregates rather than mature fibers.
At this regard, αs1-Casein results able to inhibit the nucleation phase by sequestering the Aβ peptide on its surface and thus slowing down the entire Aβ1-40 fibrillogenesis process. αs1-Casein is a natural amphiphilic almost unfolded protein. In order to be useful as an inhibitor for AD treatment, it is crucial to define a way to efficiently protect αs1-Casein and deliver it to the brain in a controlled way.
Liposomes are spherical phospholipids-based vesicles characterized by excellent biocompatibility and biodegradability, low toxicity, ability to incorporate and protect both hydrophilic and hydrophobic drugs as well as ability to cross the Blood Brain Barrier in order to access the Central Nervous System. Based on these considerations, novel proteoliposomes composed by phospholipids, cholesterol and αs1-Casein were prepared and characterized. The proteoliposome preparation protocol was optimized in order to obtain the best results. Nanosystems were characterized by different biophysics techniques such as: light scattering, zeta-potential, laurdan fluorescence, chromatography and AFM imaging
Casein-loaded proteoliposomes: novel delivery strategy to inhibit Aβ1-40 fibrillogenesis in Alzheimer disease
No full textBackground: Alzheimer's disease (AD) is a chronic and progressive syndrome, which represents the most common cause of dementia worldwide. A pathological and characteristic AD hallmark is the deposition of amyloid plaques, composed by well-ordered amyloid β-peptide (Aβ) fibers, in brain tissue. The Aβ aggregation process follows typical nucleation-polymerization kinetics, characterized by structural intermediates with specific dimensions, morphologies and cytotoxic activity. Some evidences shifted researchers’ attention to smaller soluble Aβ prefibrillar oligomers as they result the most toxic species. Therefore, novel therapeutic strategies target oligomers or prefibrillar aggregates rather than mature fibers. In particular, αs1-Casein, a natural bovine milk protein, resulted able to slow down the entire fibrillogenesis process, increase the lag-time of the nucleation phase and sequester the Aβ peptide on its surface[1].
Future perspectives and scope: to benefit from the remarkable therapeutic option represented by αs1-Casein in AD treatment, it is crucial to define a way to efficiently protect proteins and deliver them to the brain in appropriate amounts. Liposomes are spherical phospholipids-based vesicles characterized by excellent biocompatibility and biodegradability, low toxicity, ability to incorporate and protect both hydrophilic and hydrophobic drugs as well as ability to cross the Blood-Brain Barrier (BBB) in order to access the CNS. Based on these considerations, novel proteoliposomes composed by phospholipids, cholesterol and αs1-Casein were prepared in order to exploit the potentiality of liposomes in brain delivery together with the fibrillogenesis inhibition activity of αs1-Casein. The proteoliposome preparation protocol was optimized in order to obtain the best results in terms of protein-loading and stability. Nanosystems have been characterized by different biophysics techniques, such as light scattering, zeta-potential, circular dichroism, fluorescence and AFM imaging
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Amyloid β-peptide insertion in liposomes containing GM1-cholesterol domains
Full text linkNeuronal membrane damage is related to the early impairments appearing in Alzheimer's disease due to the interaction of the amyloid β-peptide (Aβ) with the phospholipid bilayer. In particular, the ganglioside GM1, present with cholesterol in lipid rafts, seems to be able to initiate Aβ aggregation on membrane. We studied the thermodynamic and structural effects of the presence of GM1 on the interaction between Aβ and liposomes, a good membrane model system. Isothermal Titration Calorimetry highlighted the importance of the presence of GM1 in recruiting monomeric Aβ toward the lipid bilayer. Light and Small Angle X-ray Scattering revealed a different pattern for GM1 containing liposomes, both before and after interaction with Aβ. The results suggest that the interaction with GM1 brings to insertion of Aβ in the bilayer, producing a structural perturbation down to the internal layers of the liposome, as demonstrated by the obtained electron density profiles
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