A giant elastic protein of molecular mass ranging from 2,993 kDa (cardiac), 3,300 kDa (psoas), to 3,700 kDa (soleus) having a kinase domain. The amino- terminal is involved in a Z line binding, and the carboxy-terminal region is bound to the myosin filament with an overlap between the counter-connectin filaments at the M line.
The repeating contractile units of the MYOFIBRIL, delimited by Z bands along its length.
The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.
The long cylindrical contractile organelles of STRIATED MUSCLE cells composed of ACTIN FILAMENTS; MYOSIN filaments; and other proteins organized in arrays of repeating units called SARCOMERES .
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Resistance and recovery from distortion of shape.
Fibers composed of MICROFILAMENT PROTEINS, which are predominately ACTIN. They are the smallest of the cytoskeletal filaments.
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
Proteins which bind calmodulin. They are found in many tissues and have a variety of functions including F-actin cross-linking properties, inhibition of cyclic nucleotide phosphodiesterase and calcium and magnesium ATPases.
Contractile tissue that produces movement in animals.
Also known as articulations, these are points of connection between the ends of certain separate bones, or where the borders of other bones are juxtaposed.
The joint that is formed by the articulation of the head of FEMUR and the ACETABULUM of the PELVIS.
A synovial hinge connection formed between the bones of the FEMUR; TIBIA; and PATELLA.
Derivatives of chondroitin which have a sulfate moiety esterified to the galactosamine moiety of chondroitin. Chondroitin sulfate A, or chondroitin 4-sulfate, and chondroitin sulfate C, or chondroitin 6-sulfate, have the sulfate esterified in the 4- and 6-positions, respectively. Chondroitin sulfate B (beta heparin; DERMATAN SULFATE) is a misnomer and this compound is not a true chondroitin sulfate.
Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed)
Products in capsule, tablet or liquid form that provide dietary ingredients, and that are intended to be taken by mouth to increase the intake of nutrients. Dietary supplements can include macronutrients, such as proteins, carbohydrates, and fats; and/or MICRONUTRIENTS, such as VITAMINS; MINERALS; and PHYTOCHEMICALS.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
Organized services to provide information on any questions an individual might have using databases and other sources. (From Random House Unabridged Dictionary, 2d ed)
Information intended for potential users of medical and healthcare services. There is an emphasis on self-care and preventive approaches as well as information for community-wide dissemination and use.
A system containing any combination of computers, computer terminals, printers, audio or visual display devices, or telephones interconnected by telecommunications equipment or cables: used to transmit or receive information. (Random House Unabridged Dictionary, 2d ed)
The attitude and behavior associated with an individual using the computer.
Familiarity and comfort in using computers efficiently.
The fusion of ceramics (porcelain) to an alloy of two or more metals for use in restorative and prosthodontic dentistry. Examples of metal alloys employed include cobalt-chromium, gold-palladium, gold-platinum-palladium, and nickel-based alloys.
The heat flow across a surface per unit area per unit time, divided by the negative of the rate of change of temperature with distance in a direction perpendicular to the surface. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Alloys that contain a high percentage of gold. They are used in restorative or prosthetic dentistry.
A tooth from which the dental pulp has been removed or is necrotic. (Boucher, Clinical Dental Terminology, 4th ed)
A prosthetic restoration that reproduces the entire surface anatomy of the visible natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin.
Use of a metal casting, usually with a post in the pulp or root canal, designed to support and retain an artificial crown.
Exploitation through misrepresentation of the facts or concealment of the purposes of the exploiter.
A type of scanning probe microscopy in which a probe systematically rides across the surface of a sample being scanned in a raster pattern. The vertical position is recorded as a spring attached to the probe rises and falls in response to peaks and valleys on the surface. These deflections produce a topographic map of the sample.
A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.
A 90-kDa protein produced by macrophages that severs ACTIN filaments and forms a cap on the newly exposed filament end. Gelsolin is activated by CALCIUM ions and participates in the assembly and disassembly of actin, thereby increasing the motility of some CELLS.
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.
Any of numerous agile, hollow-horned RUMINANTS of the genus Capra, in the family Bovidae, closely related to the SHEEP.
A species of gram-positive, rod-shaped bacteria isolated from the intestinal tract of humans and animals, the human mouth, and vagina. This organism produces the fermented product, acidophilus milk.
The white liquid secreted by the mammary glands. It contains proteins, sugar, lipids, vitamins, and minerals.
A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare.
Diseases of the domestic or wild goat of the genus Capra.
Anaerobic degradation of GLUCOSE or other organic nutrients to gain energy in the form of ATP. End products vary depending on organisms, substrates, and enzymatic pathways. Common fermentation products include ETHANOL and LACTIC ACID.
Deciduous plant rich in volatile oil (OILS, VOLATILE). It is used as a flavoring agent and has many other uses both internally and topically.

Engrailed negatively regulates the expression of cell adhesion molecules connectin and neuroglian in embryonic Drosophila nervous system. (1/616)

Engrailed is expressed in subsets of interneurons that do not express Connectin or appreciable Neuroglian, whereas other neurons that are Engrailed negative strongly express these adhesion molecules. Connectin and Neuroglian expression are virtually eliminated in interneurons when engrailed expression is driven ubiquitously in neurons, and greatly increased when engrailed genes are lacking in mutant embryos. The data suggest that Engrailed is normally a negative regulator of Connectin and neuroglian. These are the first two "effector" genes identified in the nervous system of Drosophila as regulatory targets for Engrailed. We argue that differential Engrailed expression is crucial in determining the pattern of expression of cell adhesion molecules and thus constitutes an important determinant of neuronal shape and perhaps connectivity.  (+info)

Mechanical and chemical unfolding of a single protein: a comparison. (2/616)

Is the mechanical unraveling of protein domains by atomic force microscopy (AFM) just a technological feat or a true measurement of their unfolding? By engineering a protein made of tandem repeats of identical Ig modules, we were able to get explicit AFM data on the unfolding rate of a single protein domain that can be accurately extrapolated to zero force. We compare this with chemical unfolding rates for untethered modules extrapolated to 0 M denaturant. The unfolding rates obtained by the two methods are the same. Furthermore, the transition state for unfolding appears at the same position on the folding pathway when assessed by either method. These results indicate that mechanical unfolding of a single protein by AFM does indeed reflect the same event that is observed in traditional unfolding experiments. The way is now open for the extensive use of AFM to measure folding reactions at the single-molecule level. Single-molecule AFM recordings have the added advantage that they define the reaction coordinate and expose rare unfolding events that cannot be observed in the absence of chemical denaturants.  (+info)

Proteinuria is associated with persistence of antibody to streptococcal M protein in Aboriginal Australians. (3/616)

Aboriginal communities in Northern Australia with high rates of group A streptococcal (GAS) skin infection in childhood also have high rates of renal failure in adult life. In a cross-sectional study of one such high risk community, albuminuria was used as a marker of renal disease. The prevalence of albuminuria increased from 0/52 in subjects aged 10-19 years to 10/29 (32.9%) in those aged 50 or more (P < 0.001). Antibodies to streptococcal M protein, markers of past GAS infection, were present in 48/52 (92%) at ages 10-19 years, 16/32 (50%) at ages 30-39, and 20/29 (69%) in those aged 50 or more. After allowing for the age-dependencies of albuminuria and of M protein antibodies (P < 0.001) albuminuria was significantly associated with M protein antibodies (P < 0.01). Thus, 72% of adults aged 30 or more with M protein antibodies also had albuminuria, compared with only 21% of those who were seronegative. More detailed modelling suggested that although most Aboriginal people in this community developed M protein antibodies following GAS infection in childhood, the development of proteinuria was associated with the persistence of such seropositivity into adult life. The models predicted that proteinuria developed at a mean age of 30 years in seropositive persons, at 45 years in seronegative persons who were overweight, and at 62 years in seronegative persons of normal weight. We demonstrated a clear association between evidence of childhood GAS infection and individual risk of proteinuria in adult life. This study provided a strong rationale for prevention of renal disease through the more effective control of GAS skin infections in childhood and through the prevention of obesity in adult life.  (+info)

Strength of a weak bond connecting flexible polymer chains. (4/616)

Bond dissociation under steadily rising force occurs most frequently at a time governed by the rate of loading (Evans and Ritchie, 1997 Biophys. J. 72:1541-1555). Multiplied by the loading rate, the breakage time specifies the force for most frequent failure (called bond strength) that obeys the same dependence on loading rate. The spectrum of bond strength versus log(loading rate) provides an image of the energy landscape traversed in the course of unbonding. However, when a weak bond is connected to very compliant elements like long polymers, the load applied to the bond does not rise steadily under constant pulling speed. Because of nonsteady loading, the most frequent breakage force can differ significantly from that of a bond loaded at constant rate through stiff linkages. Using generic models for wormlike and freely jointed chains, we have analyzed the kinetic process of failure for a bond loaded by pulling the polymer linkages at constant speed. We find that when linked by either type of polymer chain, a bond is likely to fail at lower force under steady separation than through stiff linkages. Quite unexpectedly, a discontinuous jump can occur in bond strength at slow separation speed in the case of long polymer linkages. We demonstrate that the predictions of strength versus log(loading rate) can rationalize conflicting results obtained recently for unfolding Ig domains along muscle titin with different force techniques.  (+info)

Different domains of the M-band protein myomesin are involved in myosin binding and M-band targeting. (5/616)

Myomesin is a 185-kDa protein located in the M-band of striated muscle where it interacts with myosin and titin, possibly connecting thick filaments with the third filament system. By using expression of epitope-tagged myomesin fragments in cultured cardiomyocytes and biochemical binding assays, we could demonstrate that the M-band targeting activity and the myosin-binding site are located in different domains of the molecule. An N-terminal immunoglobulin-like domain is sufficient for targeting to the M-band, but solid-phase overlay assays between individual N-terminal domains and the thick filament protein myosin revealed that the unique head domain contains the myosin-binding site. When expressed in cardiomyocytes, the head domains of rat and chicken myomesin showed species-specific differences in their incorporation pattern. The head domain of rat myomesin localized to a central area within the A-band, whereas the head domain of chicken myomesin was diffusely distributed in the cytoplasm. We therefore conclude that the head domain of myomesin binds to myosin but that this affinity is not sufficient for the restriction of the domain to the M-band in vivo. Instead, the neighboring immunoglobulin-like domain is essential for the precise incorporation of myomesin into the M-band, possibly because of interaction with a yet unknown protein of the sarcomere.  (+info)

Expression and functional characteristics of calpain 3 isoforms generated through tissue-specific transcriptional and posttranscriptional events. (6/616)

Calpain 3 is a nonlysosomal cysteine protease whose biological functions remain unknown. We previously demonstrated that this protease is altered in limb girdle muscular dystrophy type 2A patients. Preliminary observations suggested that its gene is subjected to alternative splicing. In this paper, we characterize transcriptional and posttranscriptional events leading to alterations involving the NS, IS1, and IS2 regions and/or the calcium binding domains of the mouse calpain 3 gene (capn3). These events can be divided into three groups: (i) splicing of exons that preserve the translation frame, (ii) inclusion of two distinct intronic sequences between exons 16 and 17 that disrupt the frame and would lead, if translated, to a truncated protein lacking domain IV, and (iii) use of an alternative first exon specific to lens tissue. In addition, expression of these isoforms seems to be regulated. Investigation of the proteolytic activities and titin binding abilities of the translation products of some of these isoforms clearly indicated that removal of these different protein segments affects differentially the biochemical properties examined. In particular, removal of exon 6 impaired the autolytic but not fodrinolytic activity and loss of exon 16 led to an increased titin binding and a loss of fodrinolytic activity. These results are likely to impact our understanding of the pathophysiology of calpainopathies and the development of therapeutic strategies.  (+info)

Mechanically driven contour-length adjustment in rat cardiac titin's unique N2B sequence: titin is an adjustable spring. (7/616)

The giant elastic protein titin is largely responsible for passive forces in cardiac myocytes. A number of different titin isoforms with distinctly different structural elements within their central I-band region are expressed in human myocardium. Their coexpression has so far prevented an understanding of the respective contributions of the isoforms to myocardial elasticity. Using isoform-specific antibodies, we find in the present study that rat myocardium expresses predominantly the small N2B titin isoform, which allows us to characterize the elastic behavior of this isoform. The extensibility and force response of N2B titin were studied by using immunoelectron microscopy and by measuring the passive force-sarcomere length (SL) relation of single rat cardiac myocytes under a variety of mechanical conditions. Experimental results were compared with the predictions of a mechanical model in which the elastic titin segment behaves as two wormlike chains, the tandem immunoglobulin (Ig) segments and the PEVK segment (rich in proline [P], glutamate [E], valine [V], and lysine [K] residues), connected in series. The overall contour length was predicted from the sequence of N2B cardiac titin. According to mechanical measurements, above approximately 2.2 microm SL titin's elastic segment extends beyond its predicted contour length. Immunoelectron microscopy indicates that a prominent source of this contour-length gain is the extension of the unique N2B sequence (located between proximal tandem Ig segment and PEVK), and that Ig domain unfolding is negligible. Thus, the elastic region of N2B cardiac titin consists of three mechanically distinct extensible segments connected in series: the tandem Ig segment, the PEVK segment, and the unique N2B sequence. Rate-dependent and repetitive stretch-release experiments indicate that both the contour-length gain and the recovery from it involve kinetic processes, probably unfolding and refolding within the N2B segment. As a result, the contour length of titin's extensible segment depends on the rate and magnitude of the preceding mechanical perturbations. The rate of recovery from the length gain is slow, ensuring that the adjusted length is maintained through consecutive cardiac cycles and that hysteresis is minimal. Thus, as a result of the extensible properties of the unique N2B sequence, the I-band region of the N2B cardiac titin isoform functions as a molecular spring that is adjustable.  (+info)

A response regulator that represses transcription of several virulence operons in the group A streptococcus. (8/616)

A search for homologs of the Bacillus subtilis PhoP response regulator in the group A streptococcus (GAS) genome revealed three good candidates. Inactivation of one of these, recently identified as csrR (J. C. Levin and M. R. Wessels, Mol. Microbiol. 30:209-219, 1998), caused the strain to produce mucoid colonies and to increase transcription of hasA, the first gene in the operon for capsule synthesis. We report here that a nonpolar insertion in this gene also increased transcription of ska (encoding streptokinase), sagA (streptolysin S), and speMF (mitogenic factor) but did not affect transcription of slo (streptolysin O), mga (multiple gene regulator of GAS), emm (M protein), scpA (complement C5a peptidase), or speB or speC (pyrogenic exotoxins B and C). The amounts of streptokinase, streptolysin S, and capsule paralleled the levels of transcription of their genes in all cases. Because CsrR represses genes unrelated to those for capsule synthesis, and because CsrA-CsrB is a global regulatory system in Escherichia coli whose mechanism is unrelated to that of these genes in GAS, the locus has been renamed covR, for "control of virulence genes" in GAS. Transcription of the covR operon was also increased in the nonpolar insertion mutant, indicating that CovR represses its own synthesis as well. All phenotypes of the covR nonpolar insertion mutant were complemented by the covR gene on a plasmid. CovR acts on operons expressed both in exponential and in stationary phase, demonstrating that the CovR-CovS pathway is separate from growth phase-dependent regulation in GAS. Therefore, CovR is the first multiple-gene repressor of virulence factors described for this important human pathogen.  (+info)

Myofiber passive stiffness is lowered by phosphorylation of the giant sarcomeric protein titin, with beneficial effects on diastolic function. Titin can be phosphorylated by cGMP-activated protein kinase (PK)G, a pathway stimulated by B-type natriuretic peptide (BNP) or PDE-5A inhibitor (sildenafil). Whether titin phosphorylation and stiffness are affected by PKG activation in vivo had not been studied. Here we examined how dogs with experimental hypertension and diastolic dysfunction, induced by renal wrapping, respond to treatment with β-blockers, sildenafil, and BNP, in terms of altered titin phosphorylation and passive stiffness.. Isolated permeabilized cardiomyocytes from left ventricular (LV) biopsies untreated (n=5), treated with β-blockers (n=7), followed by sildenafil (n=7) and BNP (n=7) were attached to a force transducer and the passive length tension relation (Fpas) was measured between 1.8 and 2.4µm sarcomere length (SL) before and after PKA and PKG administration. We also ...
Rationale: The giant protein titin plays key roles in myofilament assembly and determines the passive mechanical properties of the sarcomere. The cardiac titin molecule has 2 mayor elastic elements, the N2B and the PEVK region. Both have been suggested to determine the elastic properties of the heart with loss of function data only available for the N2B region.. Objective: The purpose of this study was to investigate the contribution of titins proline-glutamate-valine-lysine (PEVK) region to biomechanics and growth of the heart.. Methods and Results: We removed a portion of the PEVK segment (exons 219 to 225; 282 aa) that corresponds to the PEVK element of N2B titin, the main cardiac titin isoform. Adult homozygous PEVK knockout (KO) mice developed diastolic dysfunction, as determined by pressure-volume loops, echocardiography, isolated heart experiments, and muscle mechanics. Immunoelectron microscopy revealed increased strain of the N2B element, a spring region retained in the PEVK-KO. ...
Titin also known as connectin is a large filamentous protein that greatly contributes to passive myocardial stiffness. to passive myocardial stiffness in all tissue types but most in MLV least in BLA and an intermediate level in BLV. We also studied whether titin-actin interaction is regulated by S100A1/calcium and found that calcium alone or S100A1 alone did not alter passive stiffness but that combined they significantly lowered stiffness. We propose that titin-actin interaction is a viscous break that is on during diastole and off during systole. RAF265 Rabbit polyclonal to AIM1L. 1 Introduction Passive tension development in the sarcomere plays a critical role in diastolic function. The giant protein titin/connectin spans the half-sarcomere from Z-disk to M-line [1] and is responsible for the development of passive tension within the sarcomere [2]. Titin-based passive tension constitutes a large fraction of the myocardial passive tension; the other main contributor is the extracellular ...
TY - JOUR. T1 - Cardiac titin. T2 - A multifunctional giant. AU - Lewinter, Martin M.. AU - Granzier, Hendrikus Henk. PY - 2010/5/18. Y1 - 2010/5/18. N2 - Titin is responsible for the passive and restoring force of the cardiac sarcomere and makes a major contribution to the diastolic wall stress of the LV, the level of which can be tuned through differential splicing and phosphorylation. PKA and PKG phosphorylation lower stress, and PKC increases it. Changes in titin phosphorylation and titin splicing occur in cardiac disease, in addition to mutations in the titin gene. A host of titin-binding proteins have been discovered that implicate titin as a key player in the organization and development of the sarcomere, in protein turnover, and in sensing mechanical stress. Several stress-sensing signalosomes along the molecule have been discovered, of which only the FHL-based signalosome binds to a spring element (N2B). This N2B-FHL signalosome is ideally situated to sense sarcomere strain and link ...
Alpha-connectin/titin-1 exists as an elastic filament that links a thick filament with the Z-disk, keeping thick filaments centered within the sarcomere during force generation. We have shown that the connectin filament has an affinity for calcium ions and its binding site(s) is restricted to the be …
The elastic region of human soleus titin extends in situ from near the T12 epitope to near the Ti102 epitope, and is composed mainly of tandem Ig segments and the PEVK segment (Figs. 1 and 2). When slack sarcomeres are stretched, the elastic titin segment does not extend uniformly. Instead, in sarcomeres stretched to a length of ∼2.75 mm, titin extension is confined primarily to the tandem Ig segments, whereas upon further stretch, extension occurs primarily within the PEVK segment. These findings strongly support the sequential extension model of titin elasticity (Labeit and Kolmerer, 1995; Gautel and Goulding, 1996; Linke et al., 1996). To understand how it is possible that titins distinct segments extend differently, we simulated the segmental extension measurements obtained here with the mechanical properties of the single titin molecule (Kellermayer et al., 1997; Tskhovrebova et al., 1997). Modeling the tandem Ig and PEVK segments as serially linked WLC with persistence lengths of 15 and ...
PURPOSE: In this study we sought to determine whether a Titin peptide fragment can serve as a clinical biomarker for changes in muscle mass. METHODS: Mass spectrometry was used to identify Titin fragment in urine. An antibody against this Titin sequence was raised and used to develop a competitive ELISA assay for measurement in serum. Rat tissue extractions in the presence or absence of a series of proteases of interest were used to identify its enzymatic origin. A rat model of dexamethasone (DEX) induced muscle atrophy and a human 56-day bed rest study with and without vibration therapy were used to assess biological and clinical relevance. RESULTS: A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly ...
Dilated cardiomyopathy (DCM) is a frequently occurring heart disease characterized by dilation of the left or both ventricles, and systolic and diastolic dysfunctions leading to heart failure. Considering that changes in the expression of titin have been reported to modulate the passive mechanical properties of myocardium and have been associated with human cases of DCM, this study was aimed at relating the passive mechanical properties of myofibrils to the expression of titin in the left ventricle of the Bio TO-2 hamster, a genetic animal model of human DCM, during the progression of the disease. The results of this thesis suggest that a minor change in the expression of titin toward the stiffer N2B isoform occurs with disease progression in the left ventricle of the DCM hamster, but the change is too small to result in a measurable difference between the passive mechanical properties of the DCM and control myofibrils ...
The thin and thick filaments of muscle sarcomeres are interconnected by the giant protein titin, which is a scaffolding filament, signaling platform, and provider of passive tension and elasticity in myocytes. This review summarizes recent insight into the mechanisms behind how titin gene mutations cause hereditary cardiomyopathy and how titin protein is mechanically active in skeletal and cardiac myocytes. A main theme is the evolving role of titin as a modulator of contraction. Topics include strain-sensing via titin in the sarcomeric A-band as the basis for length-dependent activation, titin elastic recoil and refolding of titin domains as an energy source, and Ca2+-dependent stiffening of titin stretched during eccentric muscle contractions ...
TY - JOUR. T1 - Mechanical stability and differentially conserved physical-chemical properties of titin Ig-domains. AU - Garcia, Tzintzuni I.. AU - Oberhauser, Andres F.. AU - Braun, Werner. PY - 2009/5/15. Y1 - 2009/5/15. N2 - The mechanisms that determine mechanical stabilities of protein folds remain elusive. Our understanding of these mechanisms is vital to both bioengineering efforts and to the better understanding and eventual treatment of pathogenic mutations affecting mechanically important proteins such as titin. We present a new approach to analyze data from single-molecule force spectroscopy for different domains of the giant muscle protein titin. The region of titin found in the I-band of a sarcomere is composed of about 40 Ig-domains and is exposed to force under normal physiological conditions and connects the free-hanging ends of the myosin filaments to the Z-disc. Recent single-molecule force spectroscopy data show a mechanical hierarchy in the I-band domains. Domains near the ...
The active and passive contractile performance of skeletal muscle fibers largely depends on the myosin heavy chain (MHC) isoform and the stiffness of the titin spring, respectively. Open questions concern the relationship between titin-based stiffness and active contractile parameters, and titins importance for total passive muscle stiffness. Here, a large set of adult rabbit muscles (n = 37) was studied for titin size diversity, passive mechanical properties, and possible correlations with the fiber/MHC composition. Titin isoform analyses showed sizes between ∼3300 and 3700 kD; 31 muscles contained a single isoform, six muscles coexpressed two isoforms, including the psoas, where individual fibers expressed similar isoform ratios of 30:70 (3.4:3.3 MD). Gel electrophoresis and Western blotting of two other giant muscle proteins, nebulin and obscurin, demonstrated muscle type-dependent size differences of ≤70 kD. Single fiber and single myofibril mechanics performed on a subset of muscles ...
Connectin is scientifically formulated to deliver the key joint building blocks important for joint support. We deliver these important building blocks in an herbal delivery system to make a true one-of-a-kind effective product for efficient hip and joint support. Connectins unique, triple patented formula is one of the only joint supplements to undergo clinical trials to prove its effectiveness. We used gold-standard research parameters for our testing, which yielded improvement in an average of just 15 days*!! Our scientists know that every dog is unique, so we made this powerful joint support product in tablets, powder, and soft chews to make Connectin easy to administer! We also offer a special concentrated soft chew Connectin specifically for the Large Dog to make sure their big needs are met!. *Verified by independent veterinary researchers. Clinical data on file.. ...
upstream sequence) g.5009 aagcacaga c.-301 . . . . . . g.5069 gccactagattagtctgtgagggaaggagatgcctcttccttcccttcaatagtgggtta c.-241 . . . , 02 . . g.7616 aacccagctggcaccctctggaactacgg , gaacaatattcttcaagagaaggtcactcta c.-181 . . . . . . / g.7676 ccaaagccaggagcacagtattctcaggatctcaacaaggaagagcagaccaag / gttgct c.-121 alternative splice site ^ . . . . . . g.7736 tctgattccttacaaccttccgtaattccaggcttgtggccccaaattcagggccccacc c.-61 . . . . . . g.7796 cttccaggaacaaatcattatagtaataatttgccttcatcttccatataccaactaagc c.-1 . . . . . . g.7856 ATGTTTAACTACGAACGTCCAAAACACTTCATCCAGTCCCAAAACCCATGTGGCTCCAGA c.60 M F N Y E R P K H F I Q S Q N P C G S R p.20 . . . . . . g.7916 TTGCAGCCTCCTGGACCAGAAACCTCCAGCTTCTCTAGCCAGACCAAACAGTCTTCCATT c.120 L Q P P G P E T S S F S S Q T K Q S S I p.40 . . . . . . g.7976 ATCATCCAGCCCCGCCAGTGTACAGAGCAAAGATTTTCTGCCTCCTCAACACTGAGCTCT c.180 I I Q P R Q C T E Q R F S A S S T L S S p.60 . . . . . . g.8036 CACATCACCATGTCCTCCTCTGCTTTCCCTGCTTCTCCCCAGCAGCATGCTGGCTCCAAC c.240 H I T M S S S A F P ...
We use single molecule techniques to study the mechanical design of the giant muscle protein titin. Titin spans half the length of a muscle sarcomere and can be...
RNA-binding motif protein 20 (RBM20) is a cardiac splice regulator that adapts cardiac filling via its diverse substrates-including the sarcomeric protein titin. The molecular basis and regulation of RBM20-dependent exon exclusion are largely unknown. In tissue culture experiments, we show that the combination of RNA recognition motif (RRM) and C-terminus is necessary and sufficient for RBM20 activity, indicating an important function of the ZnF2 domain in splicing repression. Using splice reporter and in vitro binding assays targeting titin exons 241-243, we identified a minimal genomic segment that is necessary for RBM20-mediated splicing repression of the alternative exon. Here, RBM20 binds the cluster containing most RBM20 binding motifs through its RRM domain and represses the upstream and downstream introns. For subsequent exon exclusion, specific regions upstream, downstream and within the alternative exon 242 are required. Regulation of exon exclusion involves PTB4 as a novel titin ...
Imagine grabbing two snakes by the tail so that they cant wriggle off...Under the microscope muscle looks like millions of tiny pistons stac... ...Wilmanns lab and the team of Mathias Gautel an EMBL alumnus and now ...The latest study which arises from more than a decade of collaborativ...,The,giant,protein,titin,helps,build,muscles,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
The active isometric force produced by muscles varies with muscle length in accordance with the force-length relationship. Compared with isometric contractions at the same final length, force increases after active lengthening (force enhancement) and decreases after active shortening (force depression). In addition to cross-bridges, titin has been suggested to contribute to force enhancement and depression. Although titin is too compliant in passive muscles to contribute to active tension at short sarcomere lengths on the ascending limb and plateau of the force-length relationship, recent evidence suggests that activation increases titin stiffness. To test the hypothesis that titin plays a role in force enhancement and depression, we investigated isovelocity stretching and shortening in active and passive wild-type and mdm (muscular dystrophy with myositis) soleus muscles. Skeletal muscles from mdm mice have a small deletion in the N2A region of titin and show no increase in titin stiffness ...
PPAK is a repeated protein motif found in the PEVK (Pro-Glu-Val-Lys) domain of the titin protein and in a number of other proteins. Titin ( EC 2.7.11.1 ) is a giant elastic protein found in striated muscle that is a key component in the assembly and functioning of sarcomeres [ (PUBMED:15507486) ]. PPAK motifs (PPAK refers to the four amino acids found at the beginning of the motif) occur 60 times in human soleus titin [ (PUBMED:11276084) ]. PPAK motifs occur in groups of 2-12 that are separated by regions rich in glutamic acid (approximately 45%) and termed polyE segments. The charge fluctuation between the PPAK and polyE regions suggests ionic interactions between these segments and their involvement in the elastic function of titin. ...
BACKGROUND: Titin is a giant protein crucial for the assembly and elasticity of the sarcomere. Recently, titin has been linked to signal transduction through its kinase domain, which has been proposed to sense mechanical load. We developed a knockout in which expression of M-line-deficient titin can be induced in adult mice and investigated the role of the titin kinase region in cardiac function. METHODS AND RESULTS: Isolated heart experiments revealed that in titin M-line-deficient mice, the contractile response to beta-adrenergic agonists and extracellular calcium is reduced. However, the Ca(2+) sensitivity and cooperativity of activation of skinned cardiac muscle were unchanged. In knockout mice, calcium transients showed a reduced rate of calcium uptake, and expression analysis showed reduced levels of calmodulin, phospholamban, and SERCA2. Ultimately, knockout mice developed cardiac hypertrophy and heart failure, which involves protein kinase C signal transduction but not the ...
Hendrikus Granzier, PhD, studies the mechanisms whereby the giant filamentous protein titin (the largest protein known) influence muscle structure and function. His lab has shown that titin functions as a molecular spring that mediates acute responses to changing pathophysiological states of the heart. They also study the role of titin in cardiac disease, using mouse models with specific modifications in the titin gene, including deciphering the mechanisms that are responsible for gender differences in diastolic dysfunction. An additional focus of Dr. Granziers lab is on nebulin, a major muscle protein that causes a severe skeletal muscle disease in humans. Based on previous work, they hypothesize that nebulin is a determinant of calcium sensitivity of contractile force. To test this and other concepts, he uses a nebulin knockout approach in the mouse. Research is multi-faceted and uses cutting-edge techniques at levels ranging across the single molecule, single cell, muscle, and the intact ...
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The M-band is the transverse structure that cross-links the thick filaments in the center and provides a perfect alignment of the A-band in the activated sarcomere. The molecular composition of the M-bands in adult mouse skeletal muscle is fiber-type dependent. All M-bands in fast fibers contain M-protein while M-bands in slow fibers contain a significant proportion of the EH-myomesin isoform, previously detected only in embryonic heart muscle. This fiber-type specificity develops during the first postnatal weeks. However, the ratio between the amounts of myosin and of myomesin, taken as sum of both isoforms, remains nearly constant in all studied muscles. Ultrastructural analysis demonstrates that some of the soleus fibers show a diffuse appearance of the M-band, resembling the situation in the embryonic heart. A model is proposed to explain the functional consequence of differential M-band composition for the physiological and morphological properties of sarcomeres in different muscle ...
connectin: cell surface protein which binds both laminin & actin; binds thick filaments to Z lines in frog skeletal muscle; see also record for mini-titin which is a similar protein from invertebrates; titin has a protein kinase domain and a calmodulin-binding site near the C-terminus
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The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD and 165 kD. The predicted MYOM2 protein contains 1,465 amino acids. Like MYOM1, MYOM2 has a unique N-terminal domain followed by 12 repeat domains with strong homology to either fibronectin type III or immunoglobulin C2 domains. Protein sequence comparisons suggested that the MYOM2 protein and bovine M protein are identical. [provided by RefSeq, Jul 2008 ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD and 165 kD. The predicted MYOM2 protein contains 1,465 amino acids. Like MYOM1, MYOM2 has a unique N-terminal domain followed by 12 repeat domains with strong homology to either fibronectin type III or immunoglobulin C2 domains. Protein sequence comparisons suggested that the MYOM2 protein and bovine M protein are identical. [provided by RefSeq, Jul 2008 ...
Rubber band proteins can be influenced. Sildenafil inhibits a specific enzyme (phosphodiesterase 5 A), which causes the increased formation of a messenger substance (cGMP). The messenger substance activates the enzyme protein kinase G, which attaches phosphate groups to certain proteins. This so-called phosphorylation causes blood vessels to relax, which was why the potency pill Viagra originally came onto the market. The Bochum and Rochester researchers found that the cardiac muscle protein titin is also phosphorylated through the same mechanism. The titin molecules are similar to rubber bands explains the Bochum physiologist. They contribute decisively to the stiffness of the cardiac walls. The activity of the protein kinase G causes titin to relax. This makes the cardiac walls more elastic. The effect occurs within minutes of administering the drug.. ...
We identified thousands of circRNAs in the human heart and show that a subset of these circRNAs is differentially expressed in diseased hearts. The identified cardiac circRNAs conform to most of the key properties of circRNAs: (1) circ RNAs were flanked by 7- to 8-fold longer introns compared with a random set of intron, (2) we found an enrichment of inverted Alu repeats in the introns flanking the predicted circ RNAs, (3) cardiac circRNAs were not generally enriched for miRNA-binding sites, (4) circRNAs were resistant to RNase R treatment and lack poly(A) tails.. The main finding of this study is that RBM20 is crucial for the formation of a subset of circRNAs that originate from a specific region within the I-band of the titin gene (ie, PEVK and Ig repeats), a region that is known to undergo extensive alternative splicing to produce titin isoforms with the desired biomechanical properties.15 Given the known role of RBM20 in exon skipping in titins I-band, we propose the concept that RBM20, by ...
Phenotypic and genetic/allelic heterogeneity is a feature of many neuromuscular disorders, titinopathies being one of them. Hereditary Myopathy with Early Respiratory Failure (HMERF) has been considered an extremely rare disease with definite clinicopathologic hallmarks, and geographically restricted to the Northern European population with one single titin gene defect identified in previous years. The recent availability of massive parallel sequencing techniques, allowing the screening of all coding regions of the genome in undiagnosed patients, together with a growing awareness of the main muscle MRI features of the disease, has led to the discovery of a number of HMERF families and new titin mutations in the last five years ...
Molecules with defined mechanical properties are especially needed for the assembly of nanotechnological devices. A team from the University of British Columbia (Vancouver, Canada) succeeded in producing proteins with new mechanical properties through the combination of two parent protein fragments. The research group of Hongbin Li chose two different titin domains from heart muscle for their experiments. Titin, a giant molecule, is responsible for controlling the passive tension of our muscles and also pulls them together again after an extension. Depending on the type of muscle, there are differences: The titin found in heart muscle is less tensile than that found in skeletal muscle and it gives the heart the necessary stability to resist the pressure of the inflowing blood. As the parent generation, the scientists chose two globular titin domains called I27 and I32, whose mechanical properties have already been intensively researched. Both are similarly built and are composed of the protein ...
The efficient functioning of striated muscle is dependent upon the precise interactions and alignment of complex cytoskeletal networks. For example, sarcomeres, the basic contractile units of myofibrils, are comprised of uniformly arranged filament systems and regulatory proteins. The actin-containing thin filaments are anchored in the Z-lines and extend toward the middle of the sarcomere, the M-line, where they interact with the myosin-containing thick filaments to drive contraction. A third filament system is composed of single molecules of titin, the largest known vertebrate protein (∼3.7 MDa). Titin filaments span half sarcomeres, with their N-termini overlapping in the Z-lines and their C-termini overlapping in the M-lines, thus forming a continuous filament system among adjacent myofibrils (Obermann et al., 1996; Gregorio et al., 1998; Mues et al., 1998). Based on the assembly properties, molecular layout and modular structure of titin, it is proposed to act as a template for ...
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As a continuation to Blueprint Genetics recent collaborative studies on genetics of dilated cardiomyopathy (DCM) (Eur Heart J 2015 and PlosOne 2015), we performed meta-analysis of truncating titin variants in DCM.
Research team with RUB involvement reports in Genes and Development. The same mechanism that stabilizes the DNA in the cell nucleus is also important for the structure and function of vertebrate muscle cells. This has been established by RUB-researchers led by Prof. Dr. Wolfgang Linke (Institute of Physiology) in cooperation with American and German colleagues. An enzyme attaches a methyl group to the protein Hsp90, which then forms a complex with the muscle protein titin. When the researchers disrupted this protein network through genetic manipulation in zebrafish the muscle structure partly disintegrated. The scientists have thus shown that methylation also plays a significant role outside the nucleus. They published their results in Genes and Development.. Methylation in the nucleus. Enzymes, called methyltransferases, transfer methyl (CH3) groups to specific sections of the DNA in the nucleus. In this way, they mark active and inactive regions of the genes. However, not only DNA but also ...
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myomesin: protein from M-band of skeletal muscle; RefSeq NM_003970 (human); NM_008664 (mouse); XM_240481 (Myom2, rat), XM_237523 (Myom1, rat)
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In electron micrographs of the sarcomere, the M line appears as a series of parallel electron-dense lines in the central zone of the A band impliing that the M line is needed for the regular packing of the thick filaments. The M line maintains the myosin filaments in a hexagonal lattice ...
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The cover shows the La Concha bay from Ondarreta beach. The sand, in combination with the pocket watch, represents the passage of time, in reference to the travel in time done by the researchers. Starting from the sequences of the titin protein of a sel
The cover shows the La Concha bay from Ondarreta beach. The sand, in combination with the pocket watch, represents the passage of time, in reference to the travel in time done by the researchers. Starting from the sequences of the titin protein of a sel
Human Aortic Preferentially Expressed Protein-1 (APEG-1) is a novel specific smooth muscle differentiation marker thought to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). Good quality crystals that were suitable for X-ray crystallographic studies were obtained following the truncation of the 14 N-terminal amino acids of APEG-1, a region predicted to be disordered. The truncated protein (termed ΔAPEG-1) consists of a single immunoglobulin (Ig) like domain which includes an Arg-Gly-Asp (RGD) adhesion recognition motif. The RGD motif is crucial for the interaction of extracellular proteins and plays a role in cell adhesion. The X-ray structure of ΔAPEG-1 was determined and was refined to sub-atomic resolution (0.96 Å). This is the best resolution for an immunoglobulin domain structure so far. The structure adopts a Greek-key β-sandwich fold and belongs to the I (intermediate) set of the immunoglobulin superfamily. The residues lying between the β-sheets form a
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Kolmerer, B.; Witt, C. C.; Freiburg, A.; Millevoi, S.; Stier, G.; Sorimachi, H.; Pelin, K.; Carrier, L.; Schwartz, K.; Labeit, D. et al.; Gregorio, C. C.; Linke, W. A.; Labeit, S.: The titin cDNA sequence and partial genomic sequences: insights into the molecular genetics, cell biology and physiology of the titin filament system. Reviews of Physiology, Biochemistry and Pharmacology 138, pp. 19 - 55 (1999 ...
Results A pathogenic disease-related gene variant was identified in 57% of patients: 28 (18%) TTN; 7 (5%) LMNA; 16 (11%) structural cytoskeleton Z-disk genes; 9 (6%) desmosomal genes; 18 (12%) motor sarcomeric genes and 9 (6%) other genes. Baseline clinical features were similar throughout the different genotypes. A significant relationship was found between gene cluster subgroups and LVRR, with a lower rate of LVRR in structural cytoskeleton Z-disk gene mutation carriers (1/16 patients, 6%, p,0.05 vs the other subgroups). Of note, structural cytoskeleton Z-disk gene rare variants were independently and inversely associated with LVRR when adjusted for clinical predictors of LVRR (OR 0.065; 95% CI 0.008 to 0.535, p=0.011). ...
Hello Community, I am having troubles with the following (spring) geometry: As you can see it´s basically a spring element which is locked in position
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The examination of the expression profiles of other major sarcomere proteins revealed no significant preferential changes in any protein tested, other than titin (Fig. 3 C). When OD was normalized with that of MHC or actin, depending on the molecular weight, only titin was found to be significantly reduced (Fig. 3 C, bar graphs on the right). Therefore, proteins are reduced disproportionately in long-term disuse, with the effect on titin largest among the major sarcomere proteins.. In skeletal muscle, at least half of total protein is thick and thin filament based, and this fraction is lost at a faster rate than other muscle proteins in disuse (Jackman and Kandarian, 2004). The increase in the intensity of some bands in disused muscle (Fig. 3 B, arrows) indicates that the expression of nonsarcomere (or minor/unknown sarcomere) proteins may increase relative to that of the major sarcomere proteins tested in the present study.. It has been reported that gene expression is reduced for nebulin in ...
Titin (also known as connectin) is the main determinant of physiological levels of passive muscle force. experiments using Ig-domain unfolding parameters obtained in earlier single-molecule atomic force microscopy experiments recover the phenomenology of stress AG-490 relaxation and predict large-scale unfolding in titin during an extended period (>20 min) of relaxation. By contrast, immunolabeling experiments failed to demonstrate large-scale unfolding. Thus, under physiological conditions in relaxed human soleus fibers, Ig domains are more stable than predicted by atomic force microscopy experiments. Ig-domain unfolding did not become more pronounced after gelsolin treatment, suggesting that the thin filament is unlikely to significantly contribute to AG-490 the mechanical stability of the domains. We conclude that in human soleus fibers, Ig unfolding cannot solely explain stress relaxation. INTRODUCTION When nonactivated striated muscle is stretched, passive force ensues. Passive force is ...
Autor: Pizon, Véronique et al.; Genre: Zeitschriftenartikel; Im Druck veröffentlicht: 2002; Keywords: myosin; microtubules; titin; MURF2; myofibril; assembly; connectin; Titel: Transient association of titin and myosin with microtubules in nascent myofibrils directed by the MURF2 RING-finger protein
For more than 100 years, a basic physiological tenet has ruled cardiac function: A healthy beating heart will pump out the same amount of blood that it receives. Known as the Frank-Starling Law of the Heart, it is as accepted as gravity and, like gravity, is still not fully understood. Using X-ray diffraction techniques, Thomas Irving from Illinois Techs College of Science and Pieter de Tombe from Loyola University Chicago Stritch School of Medicine discovered that the protein titin may play a critical role in the nano-science behind Frank-Starling. Blood enters the heart during its diastolic phase, when cardiac muscle is relaxed and lengthened. As the heart pumps and enters into its systolic phase, the muscle forcefully contracts through the interaction of myosin and actin protein filaments. Titin serves as a kind of elastic band that stores energy when cardiac muscle is stretched and releases energy when the muscle contracts and shortens. Irving and de Tombe learned that the action of titin pulling
While we have looked at birds before, it has not been a complete coverage. Moreover the ortholog for the TTN gene has been named the SPEG complex locus. So here we use the SPEG complex locus transcripts instead of the transcript from the gene annotated as Titin. We can see that the Chinese Turtle (Pelodiscus sinensis) shows the characteristic pattern of the PEVK exons. However, none of the transcripts annotated in birds [falbicollis_ENSFALG00000003453,ggallus_ENSGALG00000028386,acarolinensis_ENSACAG00000013938,mgallopavo_ENSMGAG00000011306 tguttata_ENSTGUG00000006089 ...
Region: This exon occurs in the I-band region of the titin protein.. Domains: This exon codes for the following domain(s) - PEVK 6.. PSI: The proportion spliced-in (an estimate of the percentage of TTN transcripts that incorporate this exon based on RNAseq data) is 15% in DCM (LV tissue of 84 end-stage patients) and 37% in GTEx (LV tissue of 105 samples from Genotype-Tissue Expression project). (See Ref. 1 for details). Symmetry: This exon is symmetric, i.e. the length of the exon is a multiple of three and therefore removal of it will not alter the reading frame.. References ...
Region: This exon occurs in the I-band region of the titin protein.. Domains: This exon codes for the following domain(s) - PEVK7.. PSI: The proportion spliced-in (an estimate of the percentage of TTN transcripts that incorporate this exon based on RNAseq data) is 10% in DCM (LV tissue of 84 end-stage patients) and 25% in GTEx (LV tissue of 105 samples from Genotype-Tissue Expression project). (See Ref. 1 for details). Symmetry: This exon is symmetric, i.e. the length of the exon is a multiple of three and therefore removal of it will not alter the reading frame.. References ...
We have studied the unfolding by force of one of the immunoglobulin domains of the muscle protein titin using molecular dynamics simulations at 300 K. Previous studies, done at constant pulling rates, showed that under the effect of the force two strands connected to each other by six backbone H-bon... DRIVER (German) ...
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The structure and function of the sarcomere of striated muscle is well studied but the steps of sarcomere assembly and maintenance remain under-characterized. With the aid of chaperones and factors of the protein quality control system, muscle proteins can be folded and assembled into the contractile apparatus of the sarcomere. When sarcomere assembly is incomplete or the sarcomere becomes damaged, suites of chaperones and maintenance factors respond to repair the sarcomere. Here we show evidence of the importance of the M-line proteins, specifically myomesin, in the monitoring of sarcomere assembly and integrity in previously characterized zebrafish muscle mutants. We show that myomesin is one of the last proteins to be incorporated into the assembling sarcomere, and that in skeletal muscle, its incorporation requires connections with both titin and myosin. In diseased zebrafish sarcomeres, myomesin1a shows an early increase of gene expression, hours before chaperones respond to damaged muscle. ...
Summary: Force enhancement is absent in sarcomeres where amino acids in N2A and PEVK titin are deleted, indicating these specific regions are paramount in increasing titin stiffness in an active sarcomere. ...
A compression anastomosis ring (CAR) assembly for use in joining severed organ wall portions of a hollow organ. The assembly comprises a first portion which includes an anvil ring and a second portion which comprises a bottom ring, at least one ring element, and at least one spring element formed of a shape-memory alloy. The at least one spring element provides a restorative force and is in compressive force contact with the bottom ring and the tissue to be joined is positioned between the anvil ring and the bottom ring. A plurality of needles on one of the ring elements is operative, upon application of a closure force, to pierce the tissue and the anvil ring, holding the disk to the second portion of the CAR assembly. An applicator for applying the CAR assembly and a method for using the assembly and applicator are taught.
Honestly, based purely on my observations here, the MFM situation with the first doctor is a little unusual. Its actually pretty normal for MFMs to either be a primary doctor by themselves with no regular OB in the picture at all, or MFMs that co-manage with the OB doing the typical OB stuff while the MFM keeps an extra eye on things and directs the plan. Many MFMs dont deliver at all. My personal MFM situation is my MFM can do either, she is comfortable being a primary and delivering her patients, or co-managing (although she confided to me that she will not co-manage with just any old OB, it has to be someone she feels is a quality OB.) Ive not heard of an MFM that co-manages but takes the delivery except in emergencies...I dont really understand the OBs role with the first MFM. In any case, as long as you have an OB that you like and trust to deliver you, as far as my non-expert understanding, theres no reason they cant deliver you whether your pregnancy goes smoothly or not unless ...
Various muscular diseases are associated with changes in the elasticity of the protein titin, but whether these changes are a cause or an effect of disease has been unclear. Researchers help solve this
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This paper presents an analysis of the possible modes of behavior available to a system of two noninactivating conductance mechanisms, and indicates a good correspondence to the types of behavior exhibited by barnacle fiber. The differential equations of a simple equivalent circuit for the fiber are dealt with by means of some of the mathematical techniques of nonlinear mechanics. General features of the system are (a) a propensity to produce damped or sustained oscillations over a rather broad parameter range, and (b) considerable latitude in the shape of the oscillatory potentials. It is concluded that for cells subject to changeable parameters (either from cell to cell or with time during cellular activity), a system dominated by two noninactivating conductances can exhibit varied oscillatory and bistable behavior. See paper for details ...
BACKGROUND: Titin is a huge protein ( approximately 3 MDa) that is present in the contractile unit (sarcomere) of striated muscle and has a key role in muscle assembly and elasticity. Titin is mainly composed of two types of module (type I and II). Type I modules are found exclusively in the region of titin localised in the A band, where they are arranged in a super-repeat pattern that correlates with the ultrastructure of the thick filament. No structure of a titin type I module has been reported so far. RESULTS: We have determined the structure of a representative type I module, A71, using nuclear magnetic resonance (NMR) spectroscopy. The structure has the predicted fibronectin type III fold. Titin-specific conserved residues are either located at the putative module-module interfaces or along one side of the protein surface. Several proline residues that contribute to two stretches in a polyproline II helix conformation are solvent-exposed and line up as a continuous ribbon extending over ...
In Angewandtes online release last Thu there was a lovely paper about AFM studies of the enzyme titin kinase (TK), which is naturally activated by pulling force, a bit like a christmas cracker, but reversibly (that bit was known, but I wasnt aware of it before ...
Puchner, E. M.; Alexandrovich, A.; Kho, A. L.; Hensen, U.; Schaefer, L.; Brandmeier, B.; Graeter, F.; Grubmueller, H.; Gaub, H. E.; Gautel, M.: Mechanoenzymatics of titin kinase. Proceedings of the National Academy of Scienes of the United States of America 105 (36), S. 13385 - 13390 (2008 ...
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Titin is a giant elastomeric muscle protein that has been suggested to function as a sensor of sarcomeric stress and strain, but the mechanisms by which it does so are unresolved. To gain insight into its mechanosensory ...
For the past 5 odd months this has been the norm. Attached image is for the past 20 odd hours on my 1M line :sick: Guess thats what Telkom means with...
CS1 maint: discouraged parameter (link) "Dethklok". Connect-in. Archived from the original on 2012-03-26. Retrieved 2011-09-10 ...
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... /ˈtaɪtɪn/, also known as connectin, is a protein that in humans is encoded by the TTN gene. Titin is a giant protein, ... In 1977, Koscak Maruyama and coworkers isolated an elastic protein from muscle fiber which they called connectin. Two years ... 54 (1). Maruyama K, Matsubara S, Natori R, Nonomura Y, Kimura S (August 1977). "Connectin, an elastic protein of muscle. ... Maruyama K (May 1994). "Connectin, an elastic protein of striated muscle". Biophysical Chemistry. 50 (1-2): 73-85. doi:10.1016/ ...
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... associates with connectin through IS2, a p94-specific sequence". The Journal of Biological Chemistry. 270 (52): 31158-62. doi: ... "Suppressed disassembly of autolyzing p94/CAPN3 by N2A connectin/titin in a genetic reporter system". The Journal of Biological ...
Sorimachi H, Ono Y, Suzuki K (2000). "Skeletal muscle-specific calpain, p94, and connectin/titin: their physiological functions ... associates with connectin through IS2, a p94-specific sequence". J. Biol. Chem. 270 (52): 31158-62. doi:10.1074/jbc.270.52. ... associates with connectin through IS2, a p94-specific sequence". J. Biol. Chem. 270 (52): 31158-62. doi:10.1074/jbc.270.52. ... interacts with the extreme C-terminal region of connectin, a unique region flanked by two immunoglobulin C2 motifs". Arch. ...
CS1 maint: discouraged parameter (link) https://www.telegraphindia.com/west-bengal/calcutta-connect-in-project-chandigarh/cid/ ...
The protein is a type of connectin called a mannan-binding lectin, which plays a role in innate immunity by binding to ...
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The giant protein titin (connectin) extends from the Z-line of the sarcomere, where it binds to the thick filament (myosin) ...
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We have shown that the connectin filament has an affinity for calcium ions and its binding site(s) is restricted to the be … ... Alpha-connectin/titin-1 exists as an elastic filament that links a thick filament with the Z-disk, keeping thick filaments ... We now report the localization and the characterization of calcium-binding sites on beta-connectin. Purified beta-connectin was ... the elastic portion of connectin filaments. Furthermore, we estimated the N-terminal location of beta-connectin of various ...
connectin: cell surface protein which binds both laminin & actin; binds thick filaments to Z lines in frog skeletal muscle; see ... connectin (titin). Subscribe to New Research on connectin cell surface protein which binds both laminin & actin; binds thick ... titin; CMD1G protein, human; TTN protein, human; Z-Band region of titin; alpha-connectin; beta-connectin; titin 1; titin 2; ...
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The cell adhesion molecule, connectin, and the development of the Drosophila neuromuscular system ... The cell adhesion molecule, connectin, and the development of the Drosophila neuromuscular system ... The cell adhesion molecule, connectin, and the development of the Drosophila neuromuscular system ... The cell adhesion molecule, connectin, and the development of the Drosophila neuromuscular system ...
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Connectin filaments link thick filaments and Z lines in frog skeletal muscle as revealed by immunoelectron microscopy. K ... We suggest that connectin filaments run alongside the thick filaments, starting from a region approximately 0.15 micron from ... K Maruyama, T Yoshioka, H Higuchi, K Ohashi, S Kimura, R Natori; Connectin filaments link thick filaments and Z lines in frog ... In an earlier study connectin, an elastic protein of striated muscle, was found to be associated with "gap filaments" ...
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Monoclonal antibodies, 3B9 and 4C9, specific to connectin (also called titin), 3000 kDa elastic filamentous protein of ... Characterization of connectin-like proteins of obliquely striated muscle of a polychaete (Annelida).. Authors: Y Kawamura, J ... Anti-connectin monoclonal antibodies that react with the unc-22 gene product bind dense bodies of Caenorhabditis (Nematode) ... Monoclonal antibodies, 3B9 and 4C9, specific to connectin (also called titin), 3000 kDa elastic filamentous protein of ...
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Cummins k19 diesel engine connectin. Posted by Belt Tensioner, Automotive. Part Number 205840 Part Name Connecting rod bearing ...
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The TTN gene provides instructions for making a very large protein called titin. Learn about this gene and related health conditions.
connectin R l N ` conodont R m h g contralateral bias index Α o C A X w ...
... titin/connectin; winding filament hypothesis ...
As labeled, certain products offered for sale through your websites are drugs within the meaning of section 201(g) of the FD&C Act [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or because they are intended to affect the structure or function of the body. These products, as marketed through your websites, are also new drugs as defined by section 201(p) of the FD&C Act [21 U.S.C. § 321(p)], because they are not generally recognized as safe and effective for their labeled uses. New drugs may not be introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in section 505(a) of the FD&C Act [21 U.S.C. § 355(a)]. No approved applications pursuant to section 505 of the FD&C Act [21 U.S.C. § 355] are in effect for these products. Accordingly, their introduction or delivery for introduction into interstate commerce violates sections 301(d) and 505(a) of the FD&C ...
Connectin * LDB3 protein, human * LIM Domain Proteins * MYH7 protein, human * MYOZ2 protein, human ...
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Amphioxus connectin exhibits merged structure as invertebrate connectin in I-Band region and vertebrate connectin in A-band ... Amphioxus connectin exhibits merged structure as invertebrate connectin in I-Band region and vertebrate connectin in A-band ... Amphioxus connectin exhibits merged structure as invertebrate connectin in I-Band region and vertebrate connectin in A-band ... Amphioxus connectin exhibits merged structure as invertebrate connectin in I-Band region and vertebrate connectin in A-band ...
Gregorio, C., Perry, C. N., & Mcelhinny, A. S. (2005). Functional properties of the titin/connectin-associated proteins, the ... Gregorio, C, Perry, CN & Mcelhinny, AS 2005, Functional properties of the titin/connectin-associated proteins, the muscle- ... Gregorio, Carol ; Perry, Cynthia N. ; Mcelhinny, Abigail S. / Functional properties of the titin/connectin-associated proteins ... T1 - Functional properties of the titin/connectin-associated proteins, the muscle-specific RING finger proteins (MURFs), in ...
Titin (also known as connectin) is the main determinant of physiological. June 12, 2017. Felix Stevens ... Titin (also known as connectin) is the main determinant of physiological levels of passive muscle force. experiments using Ig- ...
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Connectin. A giant elastic protein of molecular mass ranging from 2,993 kDa (cardiac), 3,300 kDa (psoas), to 3,700 kDa (soleus ... and the carboxy-terminal region is bound to the myosin filament with an overlap between the counter-connectin filaments at the ...
190 kDa connectin-associated protein. 190 kDa titin-associated protein. Myomesin family member 1 ...
  • Connectin All-in-One Dog Joint Support Soft Chews for stiff, aging bodies or to protect young, healthy joints. (jefferspet.com)
  • In Clover Connectin Hip & Joint Soft Chews 100 ct. (holisticpetinfo.com)
  • In Clover Connectin Soft Chews for Dogs contain glucosamine, chondroitin and nutrients that help reduce inflammation and joint pain in dogs. (holisticpetinfo.com)
  • Our scientists know that every dog is unique, so we made this powerful joint support product in tablets, powder, and soft chews to make Connectin easy to administer! (inclover.com)
  • In Clover Connectin Soft Chews have a tasty pork flavor made from real and natural pork liver which makes it taste like an irresistible treat for your pet! (thepetbeastro.com)
  • Characterization of connectin-like proteins of obliquely striated muscle of a polychaete (Annelida). (scienceopen.com)
  • Connectin is an elastic protein found in vertebrate striated muscle and in some invertebrates as connectin-like proteins. (elsevier.com)
  • With regard to this sequence, although the region corresponding to the I-band is homologous to that of invertebrate connectin-like proteins and has an Ig-PEVK region similar to that of the Neanthes sp. (elsevier.com)
  • These findings revealed that amphioxus connectin has the domain structure of invertebrate connectin-like proteins at its N-terminus and that of vertebrate connectin at its C-terminus. (elsevier.com)
  • Thus, amphioxus connectin has a novel structure among known connectin-like proteins. (elsevier.com)
  • Mcelhinny, Abigail S. / Functional properties of the titin/connectin-associated proteins, the muscle-specific RING finger proteins (MURFs), in striated muscle . (elsevier.com)
  • Hu DH, Kimura S, Maruyama K. Sodium dodecyl sulfate-gel electrophoresis of connectin-like high molecular weight proteins of various types of vertebrate and invertebrate muscles. (springer.com)
  • Proteins are generally large molecules (e.g., the muscle protein titin or connectin has a single amino acid chain that is 27,000 subunits long). (newworldencyclopedia.org)
  • The giant elastic protein titin (connectin) spans the distance from the Z-line to the M-line in the striated muscle sarcomere and serves as a molecular ruler for self-assembly of sarcomere proteins during myofibrillogenesis, as well as a passive force generator (e.g. (rupress.org)
  • I decided to try the Connectin chews to see if they would help with what I had perceived as shoulder and hip issues. (jefferspet.com)
  • We have shown that the connectin filament has an affinity for calcium ions and its binding site(s) is restricted to the beta-connectin/titin-2 portion. (nih.gov)
  • We now report the localization and the characterization of calcium-binding sites on beta-connectin. (nih.gov)
  • Purified beta-connectin was digested by trypsin into 1700- and 400-kDa fragments. (nih.gov)
  • Antibodies against the 400-kDa fragment formed a sharp dense stripe at the boundary of the A and the I bands, indicating that the calcium-binding domain constitutes the N-terminal region of beta-connectin, that is, the elastic portion of connectin filaments. (nih.gov)
  • Furthermore, we estimated the N-terminal location of beta-connectin of various origins (n = 26). (nih.gov)
  • Myofibrils were treated with a solution containing 0.1 mM CaCl2 and 70 microM leupeptin to split connectin filaments into beta-connectin and a subfragment, and chain weights of these polypeptides were estimated according to their mobility in 2% polyacrylamide slab gels. (nih.gov)
  • Fortunately, contaminant beta-connectin (MW, 2000 k) was not adsorbed to Toyopearl (DEAE) column in the presence of 4M urea. (nii.ac.jp)
  • When beta-connectin was split off from alpha-connection institue 1200 kDa peptide was formed. (nii.ac.jp)
  • It was possible to isolate this peptide by sedimentation of alpha- and beta-connectin at low ionic strength. (nii.ac.jp)
  • Publications] Matsuura,Tetsu: 'Ioketion and characterization of 1200kDa peptide of α-connectin' J.Biochem.110. (nii.ac.jp)
  • Publications] Kimura,Sumiko: 'Characterization and localization of α-connectin an elastic Protein isolated from rabbit sreleteel muscle' J.Muscle Res,Cell Motil.13. (nii.ac.jp)
  • Alpha-connectin/titin-1 exists as an elastic filament that links a thick filament with the Z-disk, keeping thick filaments centered within the sarcomere during force generation. (nih.gov)
  • The giant muscle elastic protein, alpha-connectin, also called titin 1, of MW of about 3000 k was not isolated because of its insolubility and easy proteolysis. (nii.ac.jp)
  • Hu DH, Matsuno A, Terakado K, Matsuura T, Kimura S, Maruyama K. Projectin is an invertebrate connectin (titin): Isolation from crayfish claw muscle and localization in crayfish claw muscle and insect flight muscle. (springer.com)
  • Because the secondary structure of the 400-kDa fragment was changed by the binding of calcium ions, connectin filaments could be expected to alter their elasticity during the contraction-relaxation cycle of skeletal muscle. (nih.gov)
  • Connectin filaments link thick filaments and Z lines in frog skeletal muscle as revealed by immunoelectron microscopy. (rupress.org)
  • In the present immunoelectron microscopic study using polyclonal antibodies against native connectin, we have concluded that the connectin structures are directly linked to Z lines from the thick (myosin) filaments in myofibrils of skinned fibers of frog skeletal muscle. (rupress.org)
  • We suggest that connectin filaments run alongside the thick filaments, starting from a region approximately 0.15 micron from the center of the A band. (rupress.org)
  • Recently, the muscle specific RING finger (MURF) family members have established themselves as excellent candidates for linking myofibril components (including the giant, multi-functional protein, titin/connectin), with microtubules, intermediate filaments, and nuclear factors. (elsevier.com)
  • Molluscan muscle twitchin, a titin/connectin-related giant protein, regulates interactions between actin and myosin filaments at low Ca 2+ concentrations. (springer.com)
  • Whereas thick and thin filaments are responsible for active force production, the passive elasticity of muscle is dominated by titin/connectin filaments ( 1 ). (pnas.org)
  • Publications] Sonoda,Masaki: 'Mole cular shape of α-connectin,an elastic tilamentous protein of skeletal muscle' Proc,Jpn,Acad. (nii.ac.jp)
  • The standardized Cayenne Pepper used in Connectin relaxes muscles and supports joints throughout the normal aging process. (inclover.com)
  • Daily feeding of Connectin provides the body with all three essential joint building blocks (glucosamine, chondroitin, hyaluronic acid) critical to healthy joint function plus a power-packed herbal blend for noticeable, lasting results. (jefferspet.com)
  • Connectin is a patented joint supplement for dogs that combines the natural joint building blocks of glucosamine, chondroitin and hyaluronic acid with the anti-inflammatory properties of yucca and cayenne. (holisticpetinfo.com)
  • In Clover Connectin has added glucosamine and chondroitin plus additional herbs that work together to heal joints and help maintain healthy body movement. (thepetbeastro.com)
  • Monoclonal antibodies, 3B9 and 4C9, specific to connectin (also called titin), 3000 kDa elastic filamentous protein of vertebrate skeletal muscle, crossreacted with a high molecular weight protein (500 kDa) of the nematode Caenorhabditis elegans. (scienceopen.com)
  • In Clover Connectin is specially formulated to help create a natural and safe supplement to help your furry friend feel their absolute best! (thepetbeastro.com)
  • Anti-connectin monoclonal antibodies that react with the unc-22 gene product bind dense bodies of Caenorhabditis (Nematode) bodywall muscle cells. (scienceopen.com)
  • In this study, we determined the structure of the amphioxus connectin gene and analyzed its sequence based on its genomic information. (elsevier.com)
  • Changes in gene expression and content of titin (connectin) in striated muscles of chronically etihanol-fed rats]. (nih.gov)
  • Gautel M. The super-repeats of titin/connectin and their interactions: glimpses at sarcomeric assembly. (springer.com)
  • Clinical trials by independent veterinarians* showed Connectin improved mobility in dogs within 2 weeks. (holisticpetinfo.com)
  • A University study performed on Connectin by AVMHA accredited veterinarians on 88+ dogs show significant improvement in joint health within 15 days with no side effects. (holisticpetinfo.com)
  • In Clover Connectin for Large Breeds is an excellent supplement to support your dogs joint and hip function. (naturalpetwarehouse.com)
  • Connectin is natural, herbal-based joint supplement for dogs. (furryfriendsinc.com)
  • Connectin has been proven by independent research to deliver noticeable results in your dog's mobility within an average of 15 days. (inclover.com)
  • Connectin has been proven safe and effective in clinical trials by independent veterinarians. (furryfriendsinc.com)
  • For example, thyroid-releasing hormone has 234 amino acids, whereas the elastic muscle protein connectin has over 34,000. (jove.com)
  • 4000K protein, the region corresponding to the A-band has a super-repeat structure of Ig and fibronectin type 3 domains and a kinase domain near the C-terminus, which is similar to the structure of vertebrate connectin. (elsevier.com)
  • Connectin is scientifically formulated to deliver the key joint building blocks important for joint support. (inclover.com)
  • Publications] Uchida,Kiyoshi: 'Structural properties of connectin studied by ultra violet resonance Raman spectroscopy and infrared dicbroism' FEBS Letters. (nii.ac.jp)
  • Go to mycomputer properties-hardware-device manager-wireless network connectin disable. (fixya.com)
  • I then purchased Connectin based on the reviews and my dog can't gobble it up fast enough! (holisticpetinfo.com)
  • stock piling material when in connectin with the actual oil and chip contract. (illinois.gov)
  • Our results indicate that theexemplary anterior thalamic lesion eliminates about half of the en passagepathways traveling between Broca's area, passing though ventral anteriornucleus and thence to pulvinar, while affecting only twenty percent of pathwaysconnecting Broca's area with pulvinar. (ufl.edu)
  • Giving Connectin as a part of your dog's daily regime supplies all three essential joint building blocks that are critical for healthy joint function. (inclover.com)