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Journal of Genetics Jul 2018Tauopathies represent a group of neurodegenerative disorder which are characterized by the presence of tau positive specialized argyrophilic and insoluble intraneuronal... (Review)
Review
Tauopathies represent a group of neurodegenerative disorder which are characterized by the presence of tau positive specialized argyrophilic and insoluble intraneuronal and glial fibrillar lesions known as neurofibrillary tangles (NFTs). Tau is a neuron specific microtubule binding protein which is required for the integrity and functioning of neuronal cells, and hyperphosphorylation of tau and its subsequent aggregation and paired helical filaments (PHFs) and NFTs has emerged as one of the major pathogenic mechanisms of tauopathies in human and mammalian model systems. Modeling of human tauopathies in results in manifestation of associated phenotypes, and a recent study has demonstrated that similar to human and mammalian models, accumulation of insoluble tau aggregates in the form of typical neurotoxic NFTs triggers the pathogenesis of tauopathies in fly models. In view of the availability of remarkable genetic tools, tau models could be extremely useful for in-depth analysis of the role of NFTs in neurodegeneration and tau aetiology, and also for the screening of novel gene(s) and molecule(s) which suppress the toxicity of tau aggregates.
Topics: Animals; Disease Models, Animal; Drosophila melanogaster; Humans; Neurofibrillary Tangles; Neurons; Tauopathies; tau Proteins
PubMed: 30027909
DOI: No ID Found -
Journal of Molecular Recognition : JMR Dec 2019This review describes selected basics of water in biomolecular recognition. We focus on a qualitative understanding of the most important physical aspects, how these... (Review)
Review
This review describes selected basics of water in biomolecular recognition. We focus on a qualitative understanding of the most important physical aspects, how these change in magnitude between bulk water and protein environment, and how the roles that water plays for proteins arise from them. These roles include mechanical support, thermal coupling, dielectric screening, mass and charge transport, and the competition with a ligand for the occupation of a binding site. The presence or absence of water has ramifications that range from the thermodynamic binding signature of a single ligand up to cellular survival. The large inhomogeneity in water density, polarity and mobility around a solute is hard to assess in experiment. This is a source of many difficulties in the solvation of protein models and computational studies that attempt to elucidate or predict ligand recognition. The influence of water in a protein binding site on the experimental enthalpic and entropic signature of ligand binding is still a point of much debate. The strong water-water interaction in enthalpic terms is counteracted by a water molecule's high mobility in entropic terms. The complete arrest of a water molecule's mobility sets a limit on the entropic contribution of a water displacement process, while the solvent environment sets limits on ligand reactivity.
Topics: Binding Sites; Hydrogen Bonding; Ligands; Proteins; Water
PubMed: 31456282
DOI: 10.1002/jmr.2810 -
Proceedings of the National Academy of... Jan 2009Molecular imaging enables visualization of specific molecules in vivo and without substantial perturbation to the target molecule's environment. Glycans are appealing... (Review)
Review
Molecular imaging enables visualization of specific molecules in vivo and without substantial perturbation to the target molecule's environment. Glycans are appealing targets for molecular imaging but are inaccessible with conventional approaches. Classic methods for monitoring glycans rely on molecular recognition with probe-bearing lectins or antibodies, but these techniques are not well suited to in vivo imaging. In an emerging strategy, glycans are imaged by metabolic labeling with chemical reporters and subsequent ligation to fluorescent probes. This technique has enabled visualization of glycans in living cells and in live organisms such as zebrafish. Molecular imaging with chemical reporters offers a new avenue for probing changes in the glycome that accompany development and disease.
Topics: Animals; Cells; Diagnostic Imaging; Humans; Molecular Probe Techniques; Polysaccharides
PubMed: 19104067
DOI: 10.1073/pnas.0811481106 -
Proceedings of SPIE--the International... Aug 2022Advances in nanotechnology enable the detection of trace molecules from the enhanced Raman signal generated at the surface of plasmonic nanoparticles. We have developed...
Advances in nanotechnology enable the detection of trace molecules from the enhanced Raman signal generated at the surface of plasmonic nanoparticles. We have developed technology to enable super-resolution imaging of plasmonic nanoparticles, where the fluctuations in the surface enhanced Raman scattering (SERS) signal can be analyzed with localization microscopy techniques to provide nanometer spatial resolution of the emitting molecule's location. Additional work now enables the super-resolved SERS image and the corresponding spectrum to be acquired simultaneously. Here we will discuss how this approach can be applied to provide new insights into biological cells.
PubMed: 37431396
DOI: 10.1117/12.2632824 -
Philosophical Transactions. Series A,... Mar 2017Feedback traps are tools for trapping and manipulating single charged objects, such as molecules in solution. An alternative to optical tweezers and other... (Review)
Review
Feedback traps are tools for trapping and manipulating single charged objects, such as molecules in solution. An alternative to optical tweezers and other single-molecule techniques, they use feedback to counteract the Brownian motion of a molecule of interest. The trap first acquires information about a molecule's position and then applies an electric feedback force to move the molecule. Since electric forces are stronger than optical forces at small scales, feedback traps are the best way to trap single molecules without 'touching' them (e.g. by putting them in a small box or attaching them to a tether). Feedback traps can do more than trap molecules: they can also subject a target object to forces that are calculated to be the gradient of a desired potential function U(x). If the feedback loop is fast enough, it creates a virtual potential whose dynamics will be very close to those of a particle in an actual potential U(x). But because the dynamics are entirely a result of the feedback loop-absent the feedback, there is only an object diffusing in a fluid-we are free to specify and then manipulate in time an arbitrary potential U(x,t). Here, we review recent applications of feedback traps to studies on the fundamental connections between information and thermodynamics, a topic where feedback plays an even more fundamental role. We discuss how recursive maximum-likelihood techniques allow continuous calibration, to compensate for drifts in experiments that last for days. We consider ways to estimate work and heat, using them to measure fluctuating energies to a precision of ±0.03 kT over these long experiments. Finally, we compare work and heat measurements of the costs of information erasure, the Landauer limit of kT ln 2 per bit of information erased. We argue that, when you want to know the average heat transferred to a bath in a long protocol, you should measure instead the average work and then infer the heat using the first law of thermodynamics.This article is part of the themed issue 'Horizons of cybernetical physics'.
PubMed: 28115614
DOI: 10.1098/rsta.2016.0217 -
Frontiers in Pharmacology 2016Traditional medicine has a history extending back to thousands of years, and during the intervening time, man has identified the healing properties of a very broad range... (Review)
Review
Traditional medicine has a history extending back to thousands of years, and during the intervening time, man has identified the healing properties of a very broad range of plants. Globally, the use of herbal therapies to treat and manage cardiovascular disease (CVD) is on the rise. This is the second part of our comprehensive review where we discuss the mechanisms of plants and herbs used for the treatment and management of high blood pressure. Similar to the first part, PubMed and ScienceDirect databases were utilized, and the following keywords and phrases were used as inclusion criteria: hypertension, high blood pressure, herbal medicine, complementary and alternative medicine, endothelial cells, nitric oxide (NO), vascular smooth muscle cell (VSMC) proliferation, hydrogen sulfide, nuclear factor kappa-B (NF-κB), oxidative stress, and epigenetics/epigenomics. Each of the aforementioned keywords was co-joined with plant or herb in question, and where possible with its constituent molecule(s). This part deals in particular with plants that are used, albeit less frequently, for the treatment and management of hypertension. We then discuss the interplay between herbs/prescription drugs and herbs/epigenetics in the context of this disease. The review then concludes with a recommendation for more rigorous, well-developed clinical trials to concretely determine the beneficial impact of herbs and plants on hypertension and a disease-free living.
PubMed: 27014064
DOI: 10.3389/fphar.2016.00050 -
Circulation Research Jul 2009A great deal of progress has been made recently in understanding the molecules and mechanisms that regulate transendothelial migration of leukocytes, or diapedesis, a... (Review)
Review
A great deal of progress has been made recently in understanding the molecules and mechanisms that regulate transendothelial migration of leukocytes, or diapedesis, a critical step in the inflammatory response. This review focuses mainly on the active role of the endothelial cell in this process as it occurs at endothelial cell borders. It discusses some of the many molecules that have been reported to play a role in transendothelial migration and asks why so many molecules seem to be involved. The concept is emerging that diapedesis itself can be dissected into sequential steps controlled by specific molecule(s) at the endothelial cell border. Several mechanisms have been shown to play a critical role in transendothelial migration including signals derived from clustering of apically disposed intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, disruption or loosening of adherens junctions, and targeted recycling of platelet/endothelial cell adhesion molecule and other molecules from the recently described lateral border recycling compartment. A hypothesis that integrates the various known mechanisms is proposed.
Topics: Animals; Cell Movement; Endothelium, Vascular; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leukocytes; Mice; Signal Transduction; Vascular Cell Adhesion Molecule-1
PubMed: 19644057
DOI: 10.1161/CIRCRESAHA.109.200717 -
Viruses Feb 2013Dengue virus (DENV), which is transmitted by Aedes mosquitoes, causes fever and hemorrhagic disorders in humans. The virus entry process mediated through host receptor... (Review)
Review
Dengue virus (DENV), which is transmitted by Aedes mosquitoes, causes fever and hemorrhagic disorders in humans. The virus entry process mediated through host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue disease. Therefore, elucidation of the molecular mechanisms underlying virus entry is essential for an understanding of dengue pathology and for the development of effective new anti-dengue agents. DENV binds to its receptor molecules mediated through a viral envelope (E) protein, followed by incorporation of the virus-receptor complex inside cells. The fusion between incorporated virus particles and host endosome membrane under acidic conditions is mediated through the function of DENV E protein. Carbohydrate molecules, such as sulfated glycosaminoglycans (GAG) and glycosphingolipids, and carbohydrate-recognition proteins, termed lectins, inhibit virus entry. This review focuses on carbohydrate-derived entry inhibitors, and also introduces functionally related compounds with similar inhibitory mechanisms against DENV entry.
Topics: Animals; Antiviral Agents; Carbohydrates; Dengue; Dengue Virus; Humans; Membrane Fusion; Virus Internalization
PubMed: 23389466
DOI: 10.3390/v5020605 -
Biological Research Jul 2019In the growth condition(s) of plants, numerous secondary metabolites (SMs) are produced by them to serve variety of cellular functions essential for physiological... (Review)
Review
In the growth condition(s) of plants, numerous secondary metabolites (SMs) are produced by them to serve variety of cellular functions essential for physiological processes, and recent increasing evidences have implicated stress and defense response signaling in their production. The type and concentration(s) of secondary molecule(s) produced by a plant are determined by the species, genotype, physiology, developmental stage and environmental factors during growth. This suggests the physiological adaptive responses employed by various plant taxonomic groups in coping with the stress and defensive stimuli. The past recent decades had witnessed renewed interest to study abiotic factors that influence secondary metabolism during in vitro and in vivo growth of plants. Application of molecular biology tools and techniques are facilitating understanding the signaling processes and pathways involved in the SMs production at subcellular, cellular, organ and whole plant systems during in vivo and in vitro growth, with application in metabolic engineering of biosynthetic pathways intermediates.
Topics: Cell Culture Techniques; Gene Expression Regulation, Plant; Plant Growth Regulators; Plant Physiological Phenomena; Plant Roots; Plant Shoots; Plants; Secondary Metabolism; Signal Transduction; Stress, Physiological
PubMed: 31358053
DOI: 10.1186/s40659-019-0246-3