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Updated time: 17 Mar 2021
Submitted by: Nuno Santos
Abstract: Cholesterol is responsible for the plasticity of plasma membranes and is involved in physiological and pathophysiological responses. Cholesterol homeostasis is regulated by oxysterols, such as 25-hydroxycholesterol. The presence of 25-hydroxycholesterol at the membrane level has been shown to interfere with several viruses’ entry into their target cells. We used atomic force microscopy to assess the effect of 25-hydroxycholesterol on different properties of supported lipid bilayers with controlled lipid compositions. In particular, we showed that 25-hydroxycholesterol inhibits the lipid-condensing effects of cholesterol, rendering the bilayers less rigid. This study indicates that the inclusion of 25-hydroxycholesterol in plasma membranes or the conversion of part of their cholesterol content into 25-hydroxycholesterol leads to morphological alterations of the sphingomyelin (SM)-enriched domains and promotes lipid packing inhomogeneities. These changes culminate in membrane stiffness variations.
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Topic review
Updated time: 23 Aug 2021
Definition: Relevant samples are described and various problems and challenges—including 3D Challenges of 3D imaging by optical sectioning, light scattering and phototoxicity—are addressed. Furthermore, enhanced methods of wide-field or laser scanning microscopy together with some relevant examples and applications are summarized. In the future one may profit from a continuous increase in microscopic resolution, but also from molecular sensing techniques in the nanometer range using e.g., non-radiative energy transfer (FRET).
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Topic review
Updated time: 26 Nov 2021
Submitted by: Lydia Tabernero
Definition: The kinase interaction motif protein tyrosine phosphatases (KIM-PTPs), HePTP, PTPSL and STEP, are involved in the negative regulation of mitogen-activated protein kinase (MAPK) signalling pathways and are important therapeutic targets for a number of diseases.
Entry Collection : Biopharmaceuticals
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Topic review
Updated time: 26 Sep 2021
Submitted by: Ozlem Tastan Bishop
Definition: Understanding molecular mechanisms underlying the complexity of allosteric regulation in proteins has attracted considerable attention in drug discovery due to the benefits and versatility of allosteric modulators in providing desirable selectivity against protein targets while minimizing toxicity and other side effects. The proliferation of novel computational approaches for predicting ligand–protein interactions and binding using dynamic and network-centric perspectives has led to new insights into allosteric mechanisms and facilitated computer-based discovery of allosteric drugs. Although no absolute method of experimental and in silico allosteric drug/site discovery exists, current methods are still being improved. As such, the critical analysis and integration of established approaches into robust, reproducible, and customizable computational pipelines with experimental feedback could make allosteric drug discovery more efficient and reliable. In this article, we review computational approaches for allosteric drug discovery and discuss how these tools can be utilized to develop consensus workflows for in silico identification of allosteric sites and modulators with some applications to pathogen resistance and precision medicine. The emerging realization that allosteric modulators can exploit distinct regulatory mechanisms and can provide access to targeted modulation of protein activities could open opportunities for probing biological processes and in silico design of drug combinations with improved therapeutic indices and a broad range of activities.
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Topic review
Updated time: 27 Oct 2021
Submitted by: Subramanian Boopathi
Definition: Amyloid beta (Aβ) oligomers are the most neurotoxic aggregates causing neuronal death and cognitive damage. A detailed elucidation of the aggregation pathways from oligomers to fibril formation is crucial to develop therapeutic strategies for Alzheimer’s disease (AD). This review mainly focused on future perspective of Aβ peptide research using computer simulations.
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Topic review
Updated time: 21 Apr 2021
Submitted by: Si Wu
Definition: Amyloid oligomers are considered to be potential targets for the development of therapeutic strategies for a wide range of neurodegenerative diseases. However, due to the low-populated, transient, and heterogeneous nature of amyloid oligomers, they are hard to characterize by conventional bulk methods. The development of single molecule approaches provides a powerful toolkit for investigating these oligomeric intermediates as well as the complex process of amyloid aggregation at molecular resolution.
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Topic review
Updated time: 16 Sep 2021
Submitted by: Li Zhu
Definition: Cryo-electron microscopy (Cryo-EM) has become a routine technology for resolving the structure of biological macromolecules due to the resolution revolution in recent years. The specimens are typically prepared in a very thin layer of vitrified ice suspending in the holes of the perforated amorphous carbon film. However, the samples prepared by directly applying to the conventional support membranes may suffer from partial or complete denaturation caused by sticking to the air-water-interface (AWI). With the application in materials, graphene has also been used recently to improve frozen sample preparation instead of a suspended conventional amorphous thin carbon. It has been proved that graphene or graphene oxide and various chemical modifications on its surface can effectively prevent particles from adsorbing to the AWI, which improves the dispersion, adsorbed number, and orientation preference of frozen particles in the ice layer. Their excellent properties and thinner thickness can significantly reduce the background noise, allowing high-resolution three-dimensional reconstructions using a minimum data set.
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Topic review
Updated time: 12 Aug 2021
Submitted by: Jose Antonio Curiel
Definition: Fucosylated carbohydrates and glycoproteins from human breast milk are essential for the development of the gut microbiota in early life because they are selectively metabolized by bifidobacteria.
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Topic review
Updated time: 11 Aug 2021
Submitted by: Ekaterina Kovel
Definition: The simplest bioassay based on a bioluminescent system of coupled enzyme reactions was used to study toxic and antioxidant effects of a water-soluble fullerene derivative, fullerenol, with 10-12 oxygen groups (F10-12) at the enzymatic level. Toxic and antioxidant characteristics of F10-12 were compared to those of homologous fullerenols with a higher number of oxygen groups: F24-28 and F40-42. An active role of reactive oxygen species (ROS) in the bioeffects of F10-12 was demonstrated.
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Topic review
Updated time: 24 Nov 2021
Submitted by: Ren Jie Tuieng
Definition: Non-ionising ultraviolet radiation (UVR) and ionising radiation differ in their interactions with biomolecules, resulting in varied consequences. Here describing the underlying molecular interactions of radiation in the context of biological systems and their outcomes from exposure.
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