1,721,096 research outputs found
Toward a holographic brain paradigm: a lipid-centric model of brain functioning
Get PDFDue to the stimulation of neuronal membrane dipoles by action potentials, under suitable conditions coherent dipole oscillations can be formed. We argue that these dipole oscillations satisfy the weak Bose-Einstein condensate criteria of the Froehlich model of biological coherence. They can subsequently generate electromagnetic fields (EMFs) propagating in the inter-neuronal space. When neighboring neurons fire synchronously, EMFs can create interference patterns and hence form holographic images containing analog information about the sensory inputs that trigger neuronal activity. The mirror pattern projected by EMFs inside the neuron can encode information in the neuronal cytoskeleton. We outline an experimental verification of our hypothesis and its consequences for anesthesia, neurodegenerative diseases, and psychiatric states
Recent advancements in colchicine derivatives: Exploring synthesis, activities, and nanoformulations for enhanced therapeutic efficacy
No full textThe multifaceted anti-cancer properties of colchicine make it a promising candidate for tumor treatment. However, its application has been limited by poor solubility, low bioavailability, and systemic toxicity. Considerable efforts have been directed toward the development of colchicine derivatives and nanoformulations to overcome these challenges. In this review, we provide a comprehensive overview of recent advances in colchicine derivatives and nanoformulations for cancer treatment. Synthesis methods and in vitro antiproliferative assays for the reviewed derivatives and formulations are explored. Challenges, such as drug resistance and formulation optimization, are also addressed, along with future perspectives for leveraging the full potential of colchicine derivatives and their nanoformulations as innovative anti-cancer strategies, toward successful clinical applications
Molecular Insights in Psychiatry
No full textThis Special Issue included articles discussing several important psychiatric phenomena whose elucidation can be provided by cellular and subcellular molecular mechanisms [...
Computational molecular modelling as a platform for a deeper understanding of protein dynamics and rational drug design
Get PDFThermodynamic and kinetic stability of the Josephin Domain closed arrangement: evidences from replica exchange molecular dynamics
Get PDFAbstract
Background
Molecular phenomena driving pathological aggregation in neurodegenerative diseases are not completely understood yet. Peculiar is the case of Spinocerebellar Ataxia 3 (SCA3) where the conformational properties of the AT-3 N-terminal region, also called Josephin Domain (JD), play a key role in the first step of aggregation, having the JD an amyloidogenic propensity itself. For this reason, unraveling the intimate relationship between JD structural features and aggregation tendency may lead to a step forward in understanding the pathology and rationally design a cure. In this connection, computational modeling has demonstrated to be helpful in exploring the protein molecular dynamics and mechanism of action.
Results
Conformational dynamics of the JD is here finely investigated by replica exchange molecular dynamics simulations able to sample the microsecond time scale and to provide both a thermodynamic and kinetic description of the protein conformational changes. Accessible structural conformations of the JD have been identified in: open, intermediate and closed like arrangement. Data indicated the closed JD arrangement as the most likely protein arrangement. The protein transition from closed toward intermediate/open states was characterized by a rate constant higher than 700\ua0ns. This result also explains the inability of classical molecular dynamics to explore transitions from closed to open JD configuration on a time scale of hundreds of nanoseconds.
Conclusion
This work provides the first kinetic estimation of the JD transition pathway from open-like to closed-like arrangement and vice-versa, indicating the closed-like arrangement as the most likely configuration for a JD in water environment. More widely, the importance of our results is also underscored considering that the ability to provide a kinetic description of the protein conformational changes is a scientific challenge for both experimental and theoretical approaches to date.
Reviewers
This article was reviewed by Oliviero Carugo, Bojan Zagrovic
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
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