The C-terminal end segment of troponin subunit I (TnI) is a structure highly conserved among the three muscle type-specific isoforms and across vertebrate species. Partial deletion or point mutation ...in this segment impairs cardiac muscle relaxation. In the present study, we characterized the C-terminal 27 amino acid peptide of human cardiac TnI (HcTnI-C27) for its role in modulating muscle contractility. Biologically or chemically synthesized HcTnI-C27 peptide retains an epitope structure in physiological solutions similarly to that in intact TnI as recognized by an anti-TnI C-terminus monoclonal antibody (mAb TnI-1). Protein binding studies found that HcTnI-C27 retains the binding affinity for tropomyosin as previously shown with intact cardiac TnI. A restrictive cardiomyopathy mutation R192H in this segment abolishes the bindings to mAb TnI-1 and tropomyosin, demonstrating a pathogenic loss of function. Contractility studies using skinned muscle preparations demonstrated that addition of HcTnI-C27 peptide reduces the Ca2+-sensitivity of myofibrils without decreasing maximum force production. The results indicate that the C-terminal end segment of TnI is a regulatory element of troponin, which retains the native configuration in the form of free peptide to confer an effect on myofilament Ca2+-desensitization. Without negative inotropic impact, this short peptide may be developed into a novel reagent to selectively facilitate cardiac muscle relaxation at the activated state as a potential treatment for heart failure.
•The C-terminal end segment of troponin I is a highly conserved structure.•Deletion or point mutation in this segment impairs cardiac muscle relaxation.•TnI C-terminal terminal peptide retains native conformation and binds tropomyosin.•The C27 peptide reduces myofibril Ca2+-sensitivity without decreasing maximum force.•The results demonstrate a potential mechanism for the treatment of heart failure.
Calponin and transgelin (originally named SM22) are homologous cytoskeleton proteins that regulate actin-activated myosin motor functions in smooth muscle contraction and non-muscle cell motility ...during adhesion, migration, proliferation, phagocytosis, wound healing, and inflammatory responses. They are abundant cytoskeleton proteins present in multiple cell types whereas their physiological functions remain to be fully established. This focused review summarizes the evolution of genes encoding calponin and transgelin and their isoforms and discusses the structural similarity and divergence in vertebrate and invertebrate species in the context of functions in regulating cell motility. As the first literature review focusing on the evolution of the calponin-transgelin family of proteins in relevance to their structure-function relationship, the goal is to outline a foundation of current knowledge for continued investigations to understand the biological functions of calponin and transgelin in various cell types during physiological and pathological processes.
Unloading or disuse rapidly results in skeletal muscle atrophy, switching to fast-type fibers, and decreased resistance to fatigue. The recovery process is of major importance in rehabilitation for ...various clinical conditions. Here we studied mouse soleus muscle during 60 days of reloading after 4 wk of hindlimb suspension. Unloading produced significant atrophy of soleus muscle with decreased contractile force and fatigue resistance, accompanied by switches of myosin isoforms from IIa to IIx and IIb and fast troponin T to more low-molecular-weight splice forms. The total mass, fiber size, and contractile force of soleus muscle recovered to control levels after 15 days of reloading. However, the fatigue resistance showed a trend of worsening during this period with significant infiltration of inflammatory cells at days 3 and 7, indicating reloading injuries that were accompanied by active regeneration with upregulations of filamin-C, αB-crystallin, and desmin. The fatigue resistance partially recovered after 30-60 days of reloading. The expression of peroxisome proliferator-activated receptor γ coactivator 1α and mitofusin-2 showed changes parallel to that of fatigue resistance after unloading and during reloading, suggesting a causal role of decreased mitochondrial function. Slow fiber contents in the soleus muscle were increased after 30-60 days of reloading to become significantly higher than the normal level, indicating a secondary adaption to compensate for the slow recovery of fatigue resistance.
The use of multi-materials structures is nowadays one of the most sought solutions to decrease weight and reduce both emission of greenhouse gases and fuel consumption in the automotive industry. ...Dissimilar joining of aluminum (Al) alloys to steels by fusion-based welding technologies is often difficult to achieve as a result of the significant mismatch in these materials’ physical and chemical properties. Moreover, when mixed in the liquid state, hard and brittle intermetallic compounds are easily formed. Due to characteristics that include high processing speed, flexibility and energy density, multiple attempts have been made to join Al to steel using laser-based processes. This thorough review article provides a comprehensive and exhausting analysis of the recent achievements and progress on joining of Al alloys to steel by various laser-based joining processes, including laser keyhole welding, laser welding-brazing, laser-arc welding, laser-assisted friction stir welding, laser roll pressure welding and joining based on laser additive manufacturing. This paper also evaluates the joining conditions, filler materials, phase constitution, microstructure, mechanical properties and joining mechanisms associated to each process. Furthermore, special emphasis is given to factors affecting the joint strength such as welding defects, joint geometry, intermetallic compounds formation and interfacial strength. The review is then concluded with an outlook providing the summary and future trends of this field.
Many-body fermion systems are important in many branches of physics, including condensed matter, nuclear, and now cold atom physics. In many cases, the interactions between fermions can be ...approximated by a contact interaction. A recent theoretical advance in the study of these systems is the derivation of a number of exact universal relations that are predicted to be valid for all interaction strengths, temperatures, and spin compositions. These equations, referred to as the Tan relations, relate a microscopic quantity, namely, the amplitude of the high-momentum tail of the fermion momentum distribution, to the thermodynamics of the many-body system. In this work, we provide experimental verification of the Tan relations in a strongly interacting gas of fermionic atoms by measuring both the microscopic and macroscopic quantities in the same system.
The conserved C-terminal end segment of troponin I (TnI) plays a critical role in regulating muscle relaxation. This function is retained in the isolated C-terminal 27 amino acid peptide (residues ...184–210) of human cardiac TnI (HcTnI-C27): When added to skinned muscle fibers, HcTnI-C27 reduces the Ca2+-sensitivity of activated myofibrils and facilitates relaxation without decreasing the maximum force production. However, the underlying mechanism of HcTnI-C27 function is unknown. We studied the conformational preferences of HcTnI-C27 and a myopathic mutant, Arg192His, (HcTnI-C27-H). Both peptides were mainly disordered in aqueous solution with a nascent helix involving residues from Trp191 to Ile195, as shown by NMR analysis and molecular dynamics simulations. The population of nascent helix was smaller in HcTnI-C27-H than in HcTnI-C27, as shown by circular dichroism (CD) titrations. Fluorescence and isothermal titration calorimetry (ITC) showed that both peptides bound tropomyosin (αTm), with a detectably higher affinity (∼10 μM) of HcTnI-C27 than that of HcTnI-C27-H (∼15 μM), consistent with an impaired Ca2+-desensitization effect of the mutant peptide on skinned muscle strips. Upon binding to αTm, HcTnI-C27 acquired a weakly stable helix-like conformation involving residues near Trp191, as shown by transferred nuclear Overhauser effect spectroscopy and hydrogen/deuterium exchange experiments. With the potent Ca2+-desensitization effect of HcTnI-C27 on skinned cardiac muscle from a mouse model of hypertrophic cardiomyopathy, the data support that the C-terminal end domain of TnI can function as an isolated peptide with the intrinsic capacity of binding tropomyosin, providing a promising therapeutic approach to selectively improve diastolic function of the heart.
Despite much recent effort, the highest reported T c of the infinite-layer nickelates remains lower than 15 K. Here, the authors apply pressure to Pr0.82Sr0.18NiO2 thin films and observe a monotonic ...increase of T c to 31 K at 12.1 GPa, an increase that does not level off with increasing pressure.
Storing information encoded in light is critical for realizing optical buffers for all-optical signal processing and quantum memories for quantum information processing. These proposals require ...efficient interaction between atoms and a well-defined optical mode. Photonic crystal fibres can enhance light-matter interactions and have engendered a broad range of nonlinear effects; however, the storage of light has proven elusive. Here, we report the first demonstration of an optical memory in a hollow-core photonic crystal fibre. We store gigahertz-bandwidth light in the hyperfine coherence of caesium atoms at room temperature using a far-detuned Raman interaction. We demonstrate a signal-to-noise ratio of 2.6:1 at the single-photon level and a memory efficiency of 27 plus or minus 1%. Our results demonstrate the potential of a room-temperature fibre-integrated optical memory for implementing local nodes of quantum information networks.
•This study was designed to assess in vitro and in vivo antioxidant effect of APS.•APS exhibited antioxidant effect activities in AAPH-induced cell and zebrafish model.•APS has a protective effect ...against AAPH-induced oxidative stress in cell and zebrafish model.
The in vitro and in vivo antioxidant potentials of a polysaccharide isolated from aloe vera gel were investigated. Enzymatic extracts were prepared from aloe vera gel by using ten digestive enzymes including five carbohydrases and five proteases. Among them, the highest yield was obtained with the Viscozyme extract and the same extract showed the best radical scavenging activity. An active polysaccharide was purified from the Viscozyme extract using ethanol-added separation and anion exchange chromatography. Purified aloe vera polysaccharide (APS) strongly scavenged radicals including DPPH, hydroxyl and alkyl radicals. In addition, APS showed a protective effect against AAPH-induced oxidative stress and cell death in Vero cells as well as in the in vivo zebrafish model. In this study, it is proved that both the in vitro and in vivo antioxidant potentials of APS could be further utilized in relevant industrial applications.
Key points
Deficiency of dysferlin causes limb‐girdle muscular dystrophy 2B and Miyoshi myopathy with cardiac involvement that leads to dilated cardiomyopathy and heart failure. The pathogenesis and ...pathophysiology of dysferlin cardiomyopathy are not fully understood.
We studied cardiac phenotypes of young dysferlin gene knockout mice to investigate the primary pathological and pathophysiological changes.
In comparison with wild‐type controls, dysferlin‐deficient cardiomyocytes showed slower Ca2+ re‐sequestration, and dysferlin deficiency blunted the β‐adrenergic effect on relaxation and pumping function of ex vivo working hearts.
Dysferlin deficiency increased phosphorylation of ventricular myosin light chain 2, suggesting a compensatory response to the impaired cardiac lusitropic function.
The data suggest that delayed calcium re‐sequestration and post‐translational modification of myofilament proteins may provide potential targets to develop new treatments for dysferlin cardiomyopathy.
Dysferlin is a cell membrane bound protein with a role in the repair of skeletal and cardiac muscle cells. Deficiency of dysferlin leads to limb‐girdle muscular dystrophy 2B (LGMD2B) and Miyoshi myopathy. In cardiac muscle, dysferlin is located at the intercalated disc and transverse tubule membranes. Loss of dysferlin causes death of cardiomyocytes, notably in ageing hearts, leading to dilated cardiomyopathy and heart failure in LGM2B patients. To understand the primary pathogenesis and pathophysiology of dysferlin cardiomyopathy, we studied cardiac phenotypes of young adult dysferlin knockout mice and found early myocardial hypertrophy with largely compensated baseline cardiac function. Cardiomyocytes isolated from dysferlin‐deficient mice showed normal shortening and re‐lengthening velocities in the absence of external load with normal peak systolic Ca2+ but slower Ca2+ re‐sequestration than wild‐type controls. The effects of isoproterenol on relaxation velocity, left ventricular systolic pressure and stroke volume were blunted in dysferlin‐deficient mouse hearts compared with that in wild‐type hearts. Young dysferlin‐deficient mouse hearts expressed normal isoforms of myofilament proteins whereas the phosphorylation of ventricular myosin light chain 2 was significantly increased, implying a molecular response to the impaired lusitropic function. These early phenotypes of diastolic cardiac dysfunction and blunted lusitropic response of cardiac muscle to β‐adrenergic stimulation indicate a novel pathogenic mechanism of dysferlin cardiomyopathy.
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