96 research outputs found
Variational Methods for Biomolecular Modeling
Structure, function and dynamics of many biomolecular systems can be
characterized by the energetic variational principle and the corresponding
systems of partial differential equations (PDEs). This principle allows us to
focus on the identification of essential energetic components, the optimal
parametrization of energies, and the efficient computational implementation of
energy variation or minimization. Given the fact that complex biomolecular
systems are structurally non-uniform and their interactions occur through
contact interfaces, their free energies are associated with various interfaces
as well, such as solute-solvent interface, molecular binding interface, lipid
domain interface, and membrane surfaces. This fact motivates the inclusion of
interface geometry, particular its curvatures, to the parametrization of free
energies. Applications of such interface geometry based energetic variational
principles are illustrated through three concrete topics: the multiscale
modeling of biomolecular electrostatics and solvation that includes the
curvature energy of the molecular surface, the formation of microdomains on
lipid membrane due to the geometric and molecular mechanics at the lipid
interface, and the mean curvature driven protein localization on membrane
surfaces. By further implicitly representing the interface using a phase field
function over the entire domain, one can simulate the dynamics of the interface
and the corresponding energy variation by evolving the phase field function,
achieving significant reduction of the number of degrees of freedom and
computational complexity. Strategies for improving the efficiency of
computational implementations and for extending applications to coarse-graining
or multiscale molecular simulations are outlined.Comment: 36 page
Predation Risk Shapes Social Networks in Fission-Fusion Populations
Predation risk is often associated with group formation in prey, but recent advances in methods for analysing the social structure of animal societies make it possible to quantify the effects of risk on the complex dynamics of spatial and temporal organisation. In this paper we use social network analysis to investigate the impact of variation in predation risk on the social structure of guppy shoals and the frequency and duration of shoal splitting (fission) and merging (fusion) events. Our analyses revealed that variation in the level of predation risk was associated with divergent social dynamics, with fish in high-risk populations displaying a greater number of associations with overall greater strength and connectedness than those from low-risk sites. Temporal patterns of organisation also differed according to predation risk, with fission events more likely to occur over two short time periods (5 minutes and 20 minutes) in low-predation fish and over longer time scales (>1.5 hours) in high-predation fish. Our findings suggest that predation risk influences the fine-scale social structure of prey populations and that the temporal aspects of organisation play a key role in defining social systems
Brain metabolism and cerebrospinal fluid biomarkers profile of non-amnestic mild cognitive impairment in comparison to amnestic mild cognitive impairment and normal older subjects
Inhibition of cancer cell invasion and metastasis by genistein
Genistein is a small, biologically active flavonoid that is found in high amounts in soy. This important compound possesses a wide variety of biological activities, but it is best known for its ability to inhibit cancer progression. In particular, genistein has emerged as an important inhibitor of cancer metastasis. Consumption of genistein in the diet has been linked to decreased rates of metastatic cancer in a number of population-based studies. Extensive investigations have been performed to determine the molecular mechanisms underlying genistein’s antimetastatic activity, with results indicating that this small molecule has significant inhibitory activity at nearly every step of the metastatic cascade. Reports have demonstrated that, at high concentrations, genistein can inhibit several proteins involved with primary tumor growth and apoptosis, including the cyclin class of cell cycle regulators and the Akt family of proteins. At lower concentrations that are similar to those achieved through dietary consumption, genistein can inhibit the prometastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the transforming growth factor (TGF)-β signaling pathway. Several in vitro findings have been corroborated in both in vivo animal studies and in early-phase human clinical trials, demonstrating that genistein can both inhibit human cancer metastasis and also modulate markers of metastatic potential in humans, respectively. Herein, we discuss the variety of mechanisms by which genistein regulates individual steps of the metastatic cascade and highlight the potential of this natural product as a promising therapeutic inhibitor of metastasis
Gene therapy for primary immune deficiencies: a Canadian perspective
The use of gene therapy (GT) for the treatment of primary immune deficiencies (PID) including severe combined immune deficiency (SCID) has progressed significantly in the recent years. In particular, long-term studies have shown that adenosine deaminase (ADA) gene delivery into ADA-deficient hematopoietic stem cells that are then transplanted into the patients corrects the abnormal function of the ADA enzyme, which leads to immune reconstitution. In contrast, the outcome was disappointing for patients with X-linked SCID, Wiskott–Aldrich syndrome and chronic granulomatous disease who received GT followed by autologous gene corrected transplantations, as many developed hematological malignancies. The malignancies were attributed to the predilection of the viruses used for gene delivery to integrated at oncogenic areas. The availability of safer and more efficient self-inactivating lentiviruses for gene delivery has reignited the interest in GT for many PID that are now in various stages of pre-clinical studies and clinical trials. Moreover, advances in early diagnosis of PID and gene editing technology coupled with enhanced abilities to generate and manipulate stem cells ex vivo are expected to further contribute to the benefit of GT for PID. Here we review the past, the present and the future of GT for PID, with particular emphasis on the Canadian perspective
On the Coordination Behaviour of the hmta Toward Alkali Metal Cations in Presence of Perchlorate Anions
Novel Bioinformatics–Based Approach for Proteomic Biomarkers Prediction of Calpain-2 & Caspase-3 Protease Fragmentation: Application to βII-Spectrin Protein
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