Mechanisms of excitation-contraction uncoupling relevant to activity-induced muscle fatigueThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 368-372 ◽  
Author(s):  
Graham D. Lamb
Keyword(s):  
Structural Changes ◽  
Peer Review Process ◽  
Ryanodine Receptors ◽  
Low Frequency ◽  
Force Production ◽  
Dihydropyridine Receptors ◽  
Long Duration ◽  
Triad Junction ◽  
Sensor Molecules ◽  
Selection Of

If the free [Ca2+] in the cytoplasm of a skeletal muscle fiber is raised substantially for a period of seconds to minutes or to high levels just briefly, it leads to disruption of the normal excitation-contraction (E-C) coupling process and a consequent long-lasting decrease in force production. It appears that the disruption to the coupling occurs at the triad junction, where the voltage-sensor molecules (dihydropyridine receptors) normally interact with and open the Ca2+ release channels (ryanodine receptors) in the adjacent sarcoplasmic reticulum (SR). This disruption results in inadequate release of SR Ca2+ upon stimulation. Such E-C uncoupling may underlie the long-duration low-frequency fatigue that can occur after various types of exercise, as well as possibly being a contributing factor to the muscle weakness in certain muscle diseases. The process or processes causing the disruption of the coupling between the voltage sensors and the release channels is not known with certainty, but might be associated with structural changes at the triad junction, possibly caused by activation of the Ca2+-dependent protease, µ-calpain.

scholarly journals Spontaneous Ca2+ sparks and Ca2+ homeostasis in a minimal model of permeabilized ventricular myocytes

2010 ◽  
Vol 299 (6) ◽  
pp. H1996-H2008 ◽  
Author(s):  
Jana M. Hartman ◽  
Eric A. Sobie ◽  
Gregory D. Smith
Keyword(s):  
Dwell Time ◽  
Ventricular Myocytes ◽  
Molecular Level ◽  
Cell Model ◽  
Ryanodine Receptors ◽  
Low Frequency ◽  
Open Probability ◽  
Long Duration ◽  
Release Flux ◽  
Health And Disease

Many issues remain unresolved concerning how local, subcellular Ca2+ signals interact with bulk cellular concentrations to maintain homeostasis in health and disease. To aid in the interpretation of data obtained in quiescent ventricular myocytes, we present here a minimal whole cell model that accounts for both localized (subcellular) and global (cellular) aspects of Ca2+ signaling. Using a minimal formulation of the distribution of local [Ca2+] associated with a large number of Ca2+-release sites, the model simulates both random spontaneous Ca2+ sparks and the changes in myoplasmic and sarcoplasmic reticulum (SR) [Ca2+] that result from the balance between stochastic release and reuptake into the SR. Ca2+-release sites are composed of clusters of two-state ryanodine receptors (RyRs) that exhibit activation by local cytosolic [Ca2+] but no inactivation or regulation by luminal Ca2+. Decreasing RyR open probability in the model causes a decrease in aggregate release flux and an increase in SR [Ca2+], regardless of whether RyR inhibition is mediated by a decrease in RyR open dwell time or an increase in RyR closed dwell time. The same balance of stochastic release and reuptake can be achieved, however, by either high-frequency/short-duration or low-frequency/long-duration Ca2+ sparks. The results are well correlated with recent experimental observations using pharmacological RyR inhibitors and clarify those aspects of the release-reuptake balance that are inherent to the coupling between local and global Ca2+ signals and those aspects that depend on molecular-level details. The model of Ca2+ sparks and homeostasis presented here can be a useful tool for understanding changes in cardiac Ca2+ release resulting from drugs, mutations, or acquired diseases.

The nucleosome: a little variation goes a long wayThis paper is one of a selection of papers published in this Special Issue, entitled 27th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (4) ◽  
pp. 505-507 ◽  
Author(s):  
Emily Bernstein ◽  
Sandra B. Hake
Keyword(s):  
Peer Review Process ◽  
Gene Activation ◽  
Epigenetic Inheritance ◽  
Histone Variants ◽  
Post Translational Modifications ◽  
Chromatin Compaction ◽  
Cellular Processes ◽  
Chromatin Template ◽  
Mitosis And Meiosis ◽  
Selection Of

Changes in the overall structure of chromatin are essential for the proper regulation of cellular processes, including gene activation and silencing, DNA repair, chromosome segregation during mitosis and meiosis, X chromosome inactivation in female mammals, and chromatin compaction during apoptosis. Such alterations of the chromatin template occur through at least 3 interrelated mechanisms: post-translational modifications of histones, ATP-dependent chromatin remodeling, and the incorporation (or replacement) of specialized histone variants into chromatin. Of these mechanisms, the exchange of variants into and out of chromatin is the least well understood. However, the exchange of conventional histones for variant histones has distinct and profound consequences within the cell. This review focuses on the growing number of mammalian histone variants, their particular biological functions and unique features, and how they may affect the structure of the nucleosome. We propose that a given nucleosome might not consist of heterotypic variants, but rather, that only specific histone variants come together to form a homotypic nucleosome, a hypothesis that we refer to as the nucleosome code. Such nucleosomes might in turn participate in marking specific chromatin domains that may contribute to epigenetic inheritance.

Cascade control of «smart home» heating

2022 ◽  
Vol 14 (4) ◽  
pp. 82-89
Author(s):  
Sergey Polyakov ◽  
V. Akimov ◽  
A. Polukazakov
Keyword(s):  
Structural Changes ◽  
Experimental Studies ◽  
Residential Building ◽  
Heating System ◽  
Cascade Control ◽  
Virtual Object ◽  
Coolant Temperature ◽  
Home Heating ◽  
Input Signals ◽  
Selection Of

The article discusses the issues of implementing the conversion of input signals of «smart» sensors for automation of the heating system, an algorithm for calculating the parameters of measuring circuits with a nonlinear element and an operational amplifier is developed. The issues of modeling cascade control of residential building heating systems are investigated. The results of the analysis and selection of parameters of the cascade control system are presented. An algorithm implementing the operation of a virtual object is given. The structures of management of residential building objects are proposed. The method of calculating the adjustment of the controller for cascade control is given. For the heating system stand, the procedure for setting the parameters of the process of PID control of the coolant temperature is considered. The results confirming the achievability of the proposed structural changes are obtained. The results of experimental studies are presented.

Frequency-Weighted Variable-Length Controllers Using Anytime Control Strategies

2011 ◽  
Author(s):  
Gundula B. Runge ◽  
Al Ferri ◽  
Bonnie Ferri
Keyword(s):  
Time Scale ◽  
Weighting Function ◽  
Control Strategies ◽  
Low Frequency ◽  
Low Frequencies ◽  
High Frequencies ◽  
Frequency Components ◽  
Computational Resources ◽  
Weighted Variable ◽  
Selection Of

This paper considers an anytime strategy to implement controllers that react to changing computational resources. The anytime controllers developed in this paper are suitable for cases when the time scale of switching is in the order of the task execution time, that is, on the time scale found commonly with sporadically missed deadlines. This paper extends the prior work by developing frequency-weighted anytime controllers. The selection of the weighting function is driven by the expectation of the situations that would require anytime operation. For example, if the anytime operation is due to occasional and isolated missed deadlines, then the weighting on high frequencies should be larger than that for low frequencies. Low frequency components will have a smaller change over one sample time, so failing to update these components for one sample period will have less effect than with the high frequency components. An example will be included that applies the anytime control strategy to a model of a DC motor with deadzone and saturation nonlinearities.

scholarly journals DNA Polymerase: Structural Homology, Conformational Dynamics, and the Effects of Carcinogenic DNA Adducts

2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Richard G. Federley ◽  
Louis J. Romano
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Dna Adducts ◽  
Structural Changes ◽  
Dna Polymerases ◽  
Conformational Dynamics ◽  
Three Dimensional ◽  
Structural Homology ◽  
Human Right ◽  
Selection Of

DNA replication is vital for an organism to proliferate and lying at the heart of this process is the enzyme DNA polymerase. Most DNA polymerases have a similar three dimensional fold, akin to a human right hand, despite differences in sequence homology. This structural homology would predict a relatively unvarying mechanism for DNA synthesis yet various polymerases exhibit markedly different properties on similar substrates, indicative of each type of polymerase being prescribed to a specific role in DNA replication. Several key conformational steps, discrete states, and structural moieties have been identified that contribute to the array of properties the polymerases exhibit. The ability of carcinogenic adducts to interfere with conformational processes by directly interacting with the protein explicates the mutagenic consequences these adducts impose. Recent studies have identified novel states that have been hypothesised to test the fit of the nascent base pair, and have also shown the enzyme to possess a lively quality by continually sampling various conformations. This review focuses on the homologous structural changes that take place in various DNA polymerases, both replicative and those involved in adduct bypass, the role these changes play in selection of a correct substrate, and how the presence of bulky carcinogenic adducts affects these changes.

Central and peripheral contributions to neuromuscular fatigue induced by a 24-h treadmill run

2010 ◽  
Vol 108 (5) ◽  
pp. 1224-1233 ◽  
Author(s):  
Vincent Martin ◽  
Hugo Kerhervé ◽  
Laurent A. Messonnier ◽  
Jean-Claude Banfi ◽  
André Geyssant ◽  
...  
Keyword(s):  
Compound Muscle Action Potential ◽  
Vastus Lateralis ◽  
Low Frequency ◽  
Force Production ◽  
Neuromuscular Fatigue ◽  
Voluntary Activation ◽  
Knee Extensors ◽  
Function Evaluation ◽  
Central Component ◽  
Low Frequency Fatigue

This experiment investigated the fatigue induced by a 24-h running exercise (24TR) and particularly aimed at testing the hypothesis that the central component would be the main mechanism responsible for neuromuscular fatigue. Neuromuscular function evaluation was performed before, every 4 h during, and at the end of the 24TR on 12 experienced ultramarathon runners. It consisted of a determination of the maximal voluntary contractions (MVC) of the knee extensors (KE) and plantar flexors (PF), the maximal voluntary activation (%VA) of the KE and PF, and the maximal compound muscle action potential amplitude (Mmax) on the soleus and vastus lateralis. Tetanic stimulations also were delivered to evaluate the presence of low-frequency fatigue and the KE maximal muscle force production ability. Strength loss occurred throughout the exercise, with large changes observed after 24TR in MVC for both the KE and PF muscles (−40.9 ± 17.0 and −30.3 ± 12.5%, respectively; P < 0.001) together with marked reductions of %VA (−33.0 ± 21.8 and −14.8 ± 18.9%, respectively; P < 0.001). A reduction of Mmax amplitude was observed only on soleus, and no low-frequency fatigue was observed for any muscle group. Finally, KE maximal force production ability was reduced to a moderate extent at the end of the 24TR (−10.2%; P < 0.001), but these alterations were highly variable ( ± 15.7%). These results suggest that central factors are mainly responsible for the large maximal muscle torque reduction after ultraendurance running, especially on the KE muscles. Neural drive reduction may have contributed to the relative preservation of peripheral function and also affected the evolution of the running speed during the 24TR.

Electroacupuncture at Zusanli Rescues the Enteric Neuronal Loss in the Stomach of Diabetic Rats

2012 ◽  
Vol 18 (1) ◽  
pp. 5-14 ◽  
Author(s):  
Min Hu ◽  
Fan Du ◽  
Shi Liu
Keyword(s):  
High Frequency ◽  
Low Frequency ◽  
Neuronal Loss ◽  
Diabetic Rats ◽  
Enteric Neurons ◽  
Control Group ◽  
Sprague Dawley ◽  
Long Duration ◽  
Sprague Dawley Rats ◽  
Zusanli Acupoint

The purpose of this study was to investigate the effects of electroacupuncture at Zusanli acupoint on the enteric neuropathy in diabetic rats. Sprague–Dawley rats were divided into different groups depending on the total electroacupuncture span and frequency. The expression of nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5 (PGP9.5), and doublecortin was significantly decreased in the diabetic group compared with the control group. Long-term electroacupuncture at Zusanli with either high frequency or low frequency could increase the expression levels of nNOS, CHAT, PGP9.5, and doublecortin, and the increase was greater in the high-frequency group. But no obvious changes were seen in the short-term electroacupuncture groups. These results suggest that electroacupuncture at Zusanli can restore the deficiency of enteric neurons in diabetes partly but a comparative long duration of stimuli (6 weeks) is required. The increase of doublecortin may be involved in this positive process.

Expression and bioactivity of recombinant segments of human perforinThis paper is one of a selection of papers in this Special Issue, entitled International Symposium on Recent Advances in Molecular, Clinical, and Social Medicine, and has undergone the Journal's usual peer-review process.

2007 ◽  
Vol 85 (2) ◽  
pp. 203-208 ◽  
Author(s):  
Hongmei Dong ◽  
Xiaohu Xu ◽  
Mohong Deng ◽  
Xiaojun Yu ◽  
Hu Zhao ◽  
...  
Keyword(s):  
Recombinant Proteins ◽  
Fusion Proteins ◽  
Target Genes ◽  
Review Process ◽  
Peer Review Process ◽  
Nitrilotriacetic Acid ◽  
E Coli ◽  
Recombinant Plasmids ◽  
Expression Plasmids ◽  
Selection Of

The aim of the study was to prepare an active recombinant human perforin by comparing 5 candidate segments of human perforin. Full-length perforin, MAC1 (28–349 aa), MAC2 (166–369 aa), C-100, and N-60 of human perforin were selected as candidate active segments and designated, respectively, HP1, HP2, HP3, HP4, and HP5. The target genes were amplified by PCR and the products were individually subcloned into pGEM-T. The genes for HP1, HP2, HP3, and HP5 were subcloned into pET-DsbA, whereas pET-41a (+) was used as the expression vector of HP4. The fusion proteins were expressed in Escherichia coli BL21pLysS(DE3) and purified using nickel nitrilotriacetic acid (NTA) agarose affinity chromatography. The hemolysis microassay was used as an activity assay of fusion protein. From this study, we obtained the recombinant plasmids pGEM-T-HP1, -HP2, -HP3, -HP4 and -HP5, consisting of 1600, 960, 600, 300bp, and 180, respectively. From these recombinant plasmids, expression plasmids were successfully constructed and expressed in E. coli BL21pLysS(DE3). The resultant fusion proteins, affinity purified using Ni–NTA, were ~80, 58, 45, 44, and 30 kDa, respectively. The recombinant proteins were assayed for activity on hemolysis. HP2 and HP5 were the only recombinant proteins that were active in hemolysis, and the hemolytic function was concentration dependent. These results demonstrate that active recombinant forms of perforin can be synthesized in a prokaryote model. The recombinant N-60 and MAC1 (28–349 aa) of human perforin have the function of forming pores. Our study provides the experimental basis for further investigation on the application of perforin.

scholarly journals Investigation of the Effect of Sodium Selenate on Acetylcholinesterase Activity under Extremely Low Frequency Electromagnetic Field

2012 ◽  
Vol 4 (1) ◽  
Author(s):  
Ezzatollah Fathi ◽  
Raheleh Farahzadi
Keyword(s):  
Electromagnetic Field ◽  
Structural Changes ◽  
Tertiary Structure ◽  
Low Frequency ◽  
Acetylcholinesterase Activity ◽  
The Elderly ◽  
Skin Aging ◽  
Sodium Selenate ◽  
Spectroscopic Techniques ◽  
Extremely Low Frequency

Acetylcholinestrase (AChE EC 3.1.1.7) is one of the most important enzymes in nervous system, which plays a role in Alzheimer’s disease. Selenium is a vital micronutrient and many investigations have been performed about the physiological, biochemical and behavioral effects of this element, such as postponing the Alzheimer's symptoms in the elderly and delaying the initiation signs of skin aging. Recent studies have shown that this element protects various enzymes against the toxicity caused by heavy metals such as; Pb, Al, Cu and Cd. AChE activity is altered under the influence of extremely low frequency electromagnetic field (ELF-EMF). In this study, the effects of ELF-EMF, with 0.3 mT field intensity and 50, 100, 217 Hz frequencies, were investigated on the AChE, in the presence of different concentrations of sodium selenate, using UV-Visible, fluorescence and circular dichroism spectroscopic techniques. The results demonstrated that the enzyme activity declined by increasing the frequency and the amount of sodium selenate. Also, significant structural changes occurred in the secondary and tertiary structures of AChE. Our results showed that with increasing the concentration of sodium selenate transition from α-helix to β-structure was appeared in the presence of ELF-EMF. In conclusion, according to changes observed in the secondary and tertiary structure of enzyme, it is proposed that these fields are able to affect the structure and dynamics of the active site gorge of AChE.

Interactions of lactoferrin with cells involved in immune functionThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function, and Applications, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (3) ◽  
pp. 282-290 ◽  
Author(s):  
Dominique Legrand ◽  
Elisabeth Elass ◽  
Mathieu Carpentier ◽  
Joël Mazurier
Keyword(s):  
Immune Cells ◽  
Host Response ◽  
Review Process ◽  
Peer Review Process ◽  
Direct Interaction ◽  
Antimicrobial Activities ◽  
Nuclear Targeting ◽  
Cellular Targets ◽  
Anti Inflammatory ◽  
Selection Of

The antimicrobial activities of lactoferrin (Lf) depend on its capacity to bind iron and on its direct interaction with the surface of microorganisms. Its protective effect also extends to the regulation of the host response to infections. Depending on the immune status of an individual, Lf can have anti-inflammatory properties that downregulate the immune response and prevent septic shock and damage to tissues. It also acts as a promoter of the activation, differentiation, and (or) proliferation of immune cells. Although most of the anti-inflammatory activities are correlated with the neutralization of proinflammatory molecules by Lf, the promoting activity seems to be related to a direct effect of Lf on immune cells. Although the mechanisms that govern these activities are not clearly defined, and probably differ from cell to cell, several cellular targets and possible mechanisms of action are highlighted. The majority of the molecular targets at the surface of cells are multiligand receptors but, interestingly, most of them have been reported as signaling, endocytosis, and nuclear-targeting molecules. This review focuses on the known and putative mechanisms that allow the immunoregulating effect of Lf in its interactions with immune cells.

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