scholarly journals Electrical impulse characterization along actin filaments in pathological conditions

2021 ◽  
Author(s):  
Christian Hunley ◽  
Md Mohsin ◽  
Marcelo Marucho
Keyword(s):  
Actin Filaments ◽  
High Performance ◽  
Original Research ◽  
Experimental Conditions ◽  
Theoretical Formulation ◽  
Pathological Conditions ◽  
Wide Range ◽  
Biological Environment ◽  
Electrical Impulses

We present an interactive Mathematica notebook that characterizes the electrical impulses along actin filaments in both muscle and non-muscle cells for a wide range of physiological and pathological conditions. The program is based on a multi-scale (atomic → monomer → filament) approach capable of accounting for the atomistic details of a protein molecular structure, its biological environment, and their impact on the travel distance, velocity, and attenuation of monovalent ionic wave packets propagating along microfilaments. The interactive component allows investigators to conduct original research by choosing the experimental conditions (intracellular Vs in vitro), nucleotide state (ATP Vs ADP), actin isoform (alpha, gamma, beta, and muscle or non-muscle cell), as well as, a conformation model that covers a variety of mutants and wild-type (the control) actin filament. The simplicity of the theoretical formulation and the high performance of the Mathematica software enable the analysis of multiple conditions without computational restrictions. These studies may provide an unprecedented molecular understanding of why and how age, inheritance, and disease conditions induce dysfunctions in the biophysical mechanisms underlying the propagation of electrical signals along actin filaments.

Phytochemical, Analytical and Medicinal Studies of Holoptelea integrifolia Roxb. Planch - A Review

2019 ◽  
Vol 5 (4) ◽  
pp. 270-277 ◽  
Author(s):  
Vijay Kumar ◽  
Simranjeet Singh ◽  
Ragini Bhadouria ◽  
Ravindra Singh ◽  
Om Prakash
Keyword(s):  
Liquid Chromatography ◽  
Thin Layer ◽  
Thin Layer Chromatography ◽  
High Performance ◽  
Biologically Active ◽  
Toxicological Studies ◽  
Wide Range ◽  
Layer Chromatography

Holoptelea integrifolia Roxb. Planch (HI) has been used to treat various ailments including obesity, osteoarthritis, arthritis, inflammation, anemia, diabetes etc. To review the major phytochemicals and medicinal properties of HI, exhaustive bibliographic research was designed by means of various scientific search engines and databases. Only 12 phytochemicals have been reported including biologically active compounds like betulin, betulinic acid, epifriedlin, octacosanol, Friedlin, Holoptelin-A and Holoptelin-B. Analytical methods including the Thin Layer Chromatography (TLC), High-Performance Thin Layer Chromatography (HPTLC), High-Performance Liquid Chromatography (HPLC) and Liquid Chromatography With Mass Spectral (LC-MS) analysis have been used to analyze the HI. From medicinal potency point of view, these phytochemicals have a wide range of pharmacological activities such as antioxidant, antibacterial, anti-inflammatory, and anti-tumor. In the current review, it has been noticed that the mechanism of action of HI with biomolecules has not been fully explored. Pharmacology and toxicological studies are very few. This seems a huge literature gap to be fulfilled through the detailed in-vivo and in-vitro studies.

scholarly journals A multi-scale approach to describe electrical impulses propagating along actin filaments in both intracellular andin vitroconditions

RSC Advances ◽  
2018 ◽  
Vol 8 (22) ◽  
pp. 12017-12028 ◽  
Author(s):  
Christian Hunley ◽  
Diego Uribe ◽  
Marcelo Marucho
Keyword(s):  
Molecular Structure ◽  
Actin Filaments ◽  
Analytic Solution ◽  
Multi Scale ◽  
Biological Environment ◽  
Electrical Impulses

An innovative analytic solution accounting for the molecular structure, its biological environment, and their impact on electrical impulses along microfilaments.

scholarly journals Creep Behaviour and Microstructural Characterization of VAT 36 and VAT 32 Superalloys

Metals ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 877 ◽  
Author(s):  
Vagner Gobbi ◽  
Silvio Gobbi ◽  
Danieli Reis ◽  
Jorge Ferreira ◽  
José Araújo ◽  
...  
Keyword(s):  
Failure Analysis ◽  
Creep Resistance ◽  
High Performance ◽  
Creep Behaviour ◽  
Ductile Failure ◽  
Microstructural Characterization ◽  
Dislocation Slip ◽  
Creep Tests ◽  
Experimental Conditions ◽  
Wide Range

Superalloys are used primarily for the aerospace, automotive, and petrochemical industries. These applications require materials with high creep resistance. In this work, evaluation of creep resistance and microstructural characterization were carried out at two new nickel intermediate content alloys for application in aerospace industry and in high performance valves for automotive applications (alloys VAT 32 and VAT 36). The alloys are based on a high nickel chromium austenitic matrix with dispersion of intermetallic L12 and phases containing different (Nb,Ti)C carbides. Creep tests were performed at constant load, in the temperature range of 675–750 °C and stress range of 500–600 MPa. Microstructural characterization and failure analysis of fractured surfaces of crept samples were carried out with optical and scanning electron microscopy with EDS. Phases were identified by Rietveld refinement. The results showed that the superalloy VAT 32 has higher creep resistance than the VAT 36. The superior creep resistance of the alloy VAT 32 is related to its higher fraction of carbides (Nb,Ti)C and intermetallic L12 provided by the amount of carbon, titanium, and niobium in its chemical composition and subsequent heat treatment. During creep deformation these precipitates produce anchoring effect of grain boundaries, hindering relative slide between grains and therefore inhibiting crack formation. These volume defects act also as obstacles to dislocation slip and climb, decreasing the creep rate. Failure analysis of surface fractures of crept samples showed intergranular failure mechanism at crack origin for both alloys VAT 36 and VAT 32. Intergranular fracture involves nucleation, growth, and subsequent binding of voids. The final fractured portion showed transgranular ductile failure, with dimples of different shapes, generated by the formation and coalescence of microcavities with dissimilar shape and sizes. The occurrence of a given creep mechanism depends on the test conditions. At creep tests of VAT 32 and VAT 36, for lower stresses and higher temperature, possible dislocation climb over carbides and precipitates would prevail. For higher stresses and intermediate temperatures shear mechanisms involving stacking faults presumably occur over a wide range of experimental conditions.

scholarly journals Design and Evaluation of LYSO/SiPM LIGHTENING PET Detector with DTI Sampling Method

Sensors ◽  
2020 ◽  
Vol 20 (20) ◽  
pp. 5820
Author(s):  
Zhenzhou Deng ◽  
Yushan Deng ◽  
Guandong Chen
Keyword(s):  
High Performance ◽  
Sampling Method ◽  
Average Energy ◽  
High Sensitivity ◽  
Operating Conditions ◽  
Optimum Operating ◽  
Time Interval ◽  
Silicon Photomultiplier ◽  
Experimental Conditions ◽  
Wide Range

Positron emission tomography (PET) has a wide range of applications in the treatment and prevention of major diseases owing to its high sensitivity and excellent resolution. However, there is still much room for optimization in the readout circuit and fast pulse sampling to further improve the performance of the PET scanner. In this work, a LIGHTENING® PET detector using a 13 × 13 lutetium-yttrium oxyorthosilicate (LYSO) crystal array read out by a 6 × 6 silicon photomultiplier (SiPM) array was developed. A novel sampling method, referred to as the dual time interval (DTI) method, is therefore proposed to realize digital acquisition of fast scintillation pulse. A semi-cut light guide was designed, which greatly improves the resolution of the edge region of the crystal array. The obtained flood histogram shown that all the 13 × 13 crystal pixels can be clearly discriminated. The optimum operating conditions for the detector were obtained by comparing the flood histogram quality under different experimental conditions. An average energy resolution (FWHM) of 14.3% and coincidence timing resolution (FWHM) of 972 ps were measured. The experimental results demonstrated that the LIGHTENING® PET detector achieves extremely high resolution which is suitable for the development of a high performance time-of-flight PET scanner.

scholarly journals Amyloid Beta: Multiple Mechanisms of Toxicity and Only Some Protective Effects?

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Paul Carrillo-Mora ◽  
Rogelio Luna ◽  
Laura Colín-Barenque
Keyword(s):  
Amyloid Beta ◽  
Protective Effects ◽  
Protective Mechanisms ◽  
Experimental Conditions ◽  
Mechanisms Of Toxicity ◽  
Mitochondrial Alterations ◽  
Physiological Properties ◽  
Wide Range

Amyloid beta (Aβ) is a peptide of 39–43 amino acids found in large amounts and forming deposits in the brain tissue of patients with Alzheimer’s disease (AD). For this reason, it has been implicated in the pathophysiology of damage observed in this type of dementia. However, the role of Aβin the pathophysiology of AD is not yet precisely understood. Aβhas been experimentally shown to have a wide range of toxic mechanismsin vivoandin vitro, such as excitotoxicity, mitochondrial alterations, synaptic dysfunction, altered calcium homeostasis, oxidative stress, and so forth. In contrast, Aβhas also shown some interesting neuroprotective and physiological properties under certain experimental conditions, suggesting that both physiological and pathological roles of Aβmay depend on several factors. In this paper, we reviewed both toxic and protective mechanisms of Aβto further explore what their potential roles could be in the pathophysiology of AD. The complete understanding of such apparently opposed effects will also be an important guide for the therapeutic efforts coming in the future.

Understanding Biological Structures Through Exploring the Mechanical Response of Cell-Like Systems

2008 ◽  
Author(s):  
Ying Zhang ◽  
Philip R. LeDuc
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Filaments ◽  
Living Cell ◽  
Cellular Response ◽  
Cancer Metastasis ◽  
Cell Structure ◽  
Polymer Physics ◽  
Wide Range

The actin cytoskeleton provides mechanical support for the cell and influences activities such as cancer metastasis and chemotaxis. While their mechanical responses have been studied in vivo and in vitro, understanding the link between these two forms remains challenging. To explore this gap and further understand cell structure, we reconstructed the cell cytoskeleton in a membrane-like spherical liposome to mimic the cellular environment; this enables an artificial “cell like” system. Through this approach, we are pursuing a path to compare in vitro mechanics from a polymer physics perspective of individual actin filaments with the in vivo mechanics of a living cell [1]. A living cell contains many organelles, which are in a highly packed environment and require significant organization to function. The actin cytoskeleton provides both structural and organizational regulation that is essential for cellular response. Here, we first encapsulated G-actin into giant unilamellar vesicles through an electroformation technique and then polymerized them into actin filaments (F-actin) within individual vesicles. To probe their conformation, we visualized these vesicles with fluorescence and laser scanning confocal microscopy. We then used a tapping mode atomic force microscopy to determine the mechanical properties of these cell-like systems. These results provide insight into a wide range of fields and studies including polymer physics, cell biology, and biotechnology.

scholarly journals Mycobacterial Esx-3 Requires Multiple Components for Iron Acquisition

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
M. Sloan Siegrist ◽  
Magnus Steigedal ◽  
Rushdy Ahmad ◽  
Alka Mehra ◽  
Marte S. Dragset ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Iron Acquisition ◽  
Multiple Reaction Monitoring ◽  
Protein Export ◽  
Secretion Systems ◽  
Experimental Conditions ◽  
Content Type ◽  
Type Vii Secretion ◽  
Wide Range

ABSTRACT The type VII secretion systems are conserved across mycobacterial species and in many Gram-positive bacteria. While the well-characterized Esx-1 pathway is required for the virulence of pathogenic mycobacteria and conjugation in the model organism Mycobacterium smegmatis, Esx-3 contributes to mycobactin-mediated iron acquisition in these bacteria. Here we show that several Esx-3 components are individually required for function under low-iron conditions but that at least one, the membrane-bound protease MycP3 of M. smegmatis, is partially expendable. All of the esx-3 mutants tested, including the ΔmycP 3ms mutant, failed to export the native Esx-3 substrates EsxH ms and EsxG ms to quantifiable levels, as determined by targeted mass spectrometry. Although we were able to restore low-iron growth to the esx-3 mutants by genetic complementation, we found a wide range of complementation levels for protein export. Indeed, minute quantities of extracellular EsxH ms and EsxG ms were sufficient for iron acquisition under our experimental conditions. The apparent separation of Esx-3 function in iron acquisition from robust EsxG ms and EsxH ms secretion in the ΔmycP 3ms mutant and in some of the complemented esx-3 mutants compels reexamination of the structure-function relationships for type VII secretion systems. IMPORTANCE Mycobacteria have several paralogous type VII secretion systems, Esx-1 through Esx-5. Whereas Esx-1 is required for pathogenic mycobacteria to grow within an infected host, Esx-3 is essential for growth in vitro. We and others have shown that Esx-3 is required for siderophore-mediated iron acquisition. In this work, we identify individual Esx-3 components that contribute to this process. As in the Esx-1 system, most mutations that abolish Esx-3 protein export also disrupt its function. Unexpectedly, however, ultrasensitive quantitation of Esx-3 secretion by multiple-reaction-monitoring mass spectrometry (MRM-MS) revealed that very low levels of export were sufficient for iron acquisition under similar conditions. Although protein export clearly contributes to type VII function, the relationship is not absolute.

scholarly journals The making of a muscle

2012 ◽  
Vol 34 (3) ◽  
pp. 4-11 ◽  
Author(s):  
Marta Fiorotto
Keyword(s):  
High Performance ◽  
Rubber Tree ◽  
In Vitro Study ◽  
Cell Types ◽  
Experimental Manipulation ◽  
Point Of Use ◽  
Wide Range ◽  
The Difference ◽  
Environmental Causes

The skeletal musculature is usually thought of as the primary organ of locomotion, and, like the tyres of a high-performance racing car, their composition, design, preparation and plasticity can make the difference between winner and ‘wannabe’. The similarities do not end there, however. Their primary components (cells of the mesodermal layer in the embryo and latex from the rubber tree) begin their existence in locations that can be quite distant from their final point of use and in forms that bear no resemblance to the final product. Their differentiation from primary material to final product entails extensive processing, and the integration of other materials and structures are essential to ensure their function. A fundamental difference, however, is that, in the case of muscle, once the embryo is formed, the progression from relatively undifferentiated mesodermal cells to the final structures is on autopilot, provided there are no contextual aberrations either from genetic or environmental causes. Our current understanding of how muscles develop is a synthesis of observations made on a wide array of organisms, including nematode worms, fruitflies, fish, frogs, birds and various mammals, as well as from the in vitro study of cells isolated from these species. The study of myogenesis in mammals, although less amenable to experimental manipulation, has been facilitated by the recent advances in mouse genetic engineering which has enabled the function of individual genes and cell types to be investigated, as well as the lineage of cells to be traced back to their origin. In this rapid trek through the life of a muscle, how the production of a mature functional muscle from its early inception is orchestrated will be outlined in exceedingly broad strokes so as to convey the wide range of processes that must be engaged in order to generate a functional muscle. Hopefully, enough information will be provided to encourage those interested to explore further.

Rapid qualitative profiling of metabolites present in Fusarium solani, a rhizospheric fungus derived from Senna spectabilis, using GC/MS and UPLC-QTOF/MSE techniques assisted by UNIFI information system

2020 ◽  
Vol 26 (4) ◽  
pp. 281-291
Author(s):  
Natália Carolina Vieira ◽  
Patrícia Cardoso Cortelo ◽  
Ian Castro-Gamboa
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Ethyl Acetate ◽  
Fusarium Solani ◽  
High Performance ◽  
Ethyl Acetate Extract ◽  
Bioactive Metabolites ◽  
Flight Mass Spectrometry ◽  
Wide Range

Fungi are an important source of natural products found in a variety of plant species. A wide range of methods for the detection of metabolites present in fungi have been reported in the literature. The search for methodologies that allow the rapid detection of compounds present in crude extracts is crucial to enable the metabolite annotation doing a qualitative analysis of the complex matrix. Mass spectrometry is an important ally when it comes to in silico detection of previously reported metabolites. In this work, the ethyl acetate extract of Fusarium solani was analyzed by gas chromatography coupled to mass spectrometry (GC/MS) after derivatization process. The ethyl acetate extract was also investigated by liquid chromatography coupled with high-resolution tandem mass spectrometry assisted by the UNIFI software system. A library containing previously reported metabolites from the Fusarium genus was added to the UNIFI platform. Simultaneously, the extract was analyzed through anticholinesterase and antifungal assays. The analysis of the derivatized extract by GC/MS led to the putative identification of five metabolites, and the investigation using Ultra-High Performance Liquid Chromatography - Quadrupole Time-of-Flight Mass Spectrometry (UPLC-QTOF) analysis in data-independent acquisition mode (mass spectrometry) led to the annotation of 15 compounds present in the built-in Fusarium library added to the UNIFI system. The Fusarium solani extract showed potential anticholinesterase and in vitro antifungal activity supported by the detection of bioactive metabolites.

A Distributed Computing Tool for Generating Neural Simulation Databases

2006 ◽  
Vol 18 (12) ◽  
pp. 2923-2927 ◽  
Author(s):  
Robert J. Calin-Jageman ◽  
Paul S. Katz
Keyword(s):  
High Performance ◽  
Large Scale ◽  
Model Neuron ◽  
Scale Model ◽  
Large Set ◽  
Experimental Conditions ◽  
Entry Level ◽  
Neural Simulation ◽  
Wide Range ◽  
Parameter Values

After developing a model neuron or network, it is important to systematically explore its behavior across a wide range of parameter values or experimental conditions, or both. However, compiling a very large set of simulation runs is challenging because it typically requires both access to and expertise with high-performance computing facilities. To lower the barrier for large-scale model analysis, we have developed NeuronPM, a client/server application that creates a “screen-saver” cluster for running simulations in NEURON (Hines & Carnevale, 1997). NeuronPM provides a user-friendly way to use existing computing resources to catalog the performance of a neural simulation across a wide range of parameter values and experimental conditions. The NeuronPM client is a Windows-based screen saver, and the NeuronPM server can be hosted on any Apache/PHP/MySQL server. During idle time, the client retrieves model files and work assignments from the server, invokes NEURON to run the simulation, and returns results to the server. Administrative panels make it simple to upload model files, define the parameters and conditions to vary, and then monitor client status and work progress. NeuronPM is open-source freeware and is available for download at http://neuronpm.homeip.net . It is a useful entry-level tool for systematically analyzing complex neuron and network simulations.

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