A major obstacle limiting gene therapy for diseases of the heart and skeletal muscles is an inability to deliver genes systemically to muscles of an adult organism. Systemic gene transfer to striated muscles is hampered by the vascular endothelium, which represents a barrier to distribution of vectors via the circulation. Here we show the first evidence of widespread transduction of both cardiac and skeletal muscles in an adult mammal, after a single intravenous administration of recombinant adeno-associated virus pseudotype 6 vectors. The inclusion of vascular endothelium growth factor/vascular permeability factor, to achieve acute permeabilization of the peripheral microvasculature, enhanced tissue transduction at lower vector doses. This technique enabled widespread muscle-specific expression of a functional micro-dystrophin in the skeletal muscles of dystrophin-deficient mdx mice, which model Duchenne muscular dystrophy. We propose that these methods may be applicable for systemic delivery of a wide variety of genes to the striated muscles of adult mammals.
striated
In situ hybridisation (a-d) and schematic representation (e-f) of Ch-muscleLim (a, b), Ch-ldb3/zasp (c, d) expression mainly restricte to the developing radial canal endoderm (a-f). Ch-myhc-st-positive subumbrella striated muscle precursor cells (arrows, compare with Fig. 3m) do not show muscleLim- or ldb3/zasp-expression. Stages: medusal bud (a,c,e), young medusa (b,d,f). All oral views.
Striated muscle tissue is a muscle tissue that features repeating functional units called sarcomeres. The presence of sarcomeres manifests as a series of bands visible along the muscle fibers, which is responsible for the striated appearance observed in microscopic images of this tissue. There are two types of striated muscle:
Unlike skeletal and cardiac muscle tissue, smooth muscle tissue is not striated since there are no sarcomeres present. Skeletal muscles are attached to some component of the skeleton, and smooth muscle is found in hollow structures such as the walls of intestines or blood vessels. The fibres of striated muscle have a cylindrical shape with blunt ends, whereas those in smooth muscle are spindle-like with tapered ends. Striated muscle tissue has more mitochondria than smooth muscle. Both smooth muscle cells and cardiac muscle cells have a single nucleus, and skeletal muscle cells have many nuclei.[6]
The main function of striated muscle tissue is to create force and contract. These contractions in cardiac muscle will pump blood throughout the body. In skeletal muscle the contractions enable breathing, movement, and posture maintenance.[1]
Recordings of the change in tension in striated muscle after a sudden alteration of the length have made it possible to suggest how the force between the thick and thin muscle filaments may be generated.
The striated testis is an imaging finding that is seen in symptomatic and asymptomatic individuals. In geriatric people, the most common cause is interstitial fibrosis. In adolescent individuals, a few of the causes include trauma, neoplasm including non Hodgkin lymphoma, infection and testicular infarction 1.
Activation of striated muscle is a calcium-dependent process, with initial studies describing calcium binding as a switch that can turn regulated thin filaments "on" or "off". The basic regulatory apparatus is an actin-associated complex composed of tropomyosin (Tm) and troponin (Tn).
While early structural studies described regulation in terms of a three state model for the thin filament (blocked, closed, and open) this basic model lacks the ability to explain much of the behavior observed in striated muscle regulation. Developing more explicit and complex models is an area fraught with difficulty, and has been attempted by many groups. Here, we simplify the system in an elegant way to give a remarkably accurate description of a wide range of experimental behaviors using actin sliding velocities as an approximation of the level of activation observed in a system of thin filaments. Through the development of a simple steady-state model, we are able to define the level of activation of a thin filament and account for much of the behavior witnessed in regulation using only well defined parameters of actin-myosin binding kinetics and calcium regulation of striated muscle.
Striated muscle contraction is a process whereby force is generated within striated muscle tissue, resulting in a change in muscle geometry, or in short, increased force being exerted on the tendons. Force generation involves a chemo-mechanical energy conversion step that is carried out by the actin/myosin complex activity, which generates force through ATP hydrolysis. Striated muscle is a type of muscle composed of myofibrils, containing repeating units called sarcomeres, in which the contractile myofibrils are arranged in parallel to the axis of the cell, resulting in transverse or oblique striations observable at the level of the light microscope.Here striated muscle contraction is represented on the basis of calcium binding to the troponin complex, which exposes the active sites of actin. Once the active sites of actin are exposed, the myosin complex bound to ADP can bind actin and the myosin head can pivot, pulling the thin actin and thick myosin filaments past one another. Once the myosin head pivots, ADP is ejected, a fresh ATP can be bound and the energy from the hydrolysis of ATP to ADP is channeled into kinetic energy by resetting the myosin head. With repeated rounds of this cycle the sarcomere containing the thin and thick filaments effectively shortens, forming the basis of muscle contraction.
Contraction in striated and cardiac muscles is regulated by the motions of a Ca(2+)-sensitive tropomyosin/troponin switch. In contrast, troponin is absent in other muscle types and in nonmuscle cells, and actomyosin regulation is myosin-linked. Here we report an unusual crystal structure at 2 ...
Contraction in striated and cardiac muscles is regulated by the motions of a Ca(2+)-sensitive tropomyosin/troponin switch. In contrast, troponin is absent in other muscle types and in nonmuscle cells, and actomyosin regulation is myosin-linked. Here we report an unusual crystal structure at 2.7 A of the C-terminal 31 residues of rat striated-muscle alpha-tropomyosin (preceded by a fragment of the GCN4 leucine zipper). The C-terminal 22 residues (263-284) of the structure do not form a two-stranded alpha-helical coiled coil as does the rest of the molecule, but here the alpha-helices splay apart and are stabilized by the formation of a tail-to-tail dimer with a symmetry-related molecule. The site of splaying involves a small group of destabilizing core residues that is present only in striated muscle tropomyosin isoforms. These results reveal a specific recognition site for troponin T and clarify the physical basis for the unique regulatory mechanism of striated muscles.
From colonization to (post)industrial era, recreation guised as preservation of wilderness is a concept and ongoing topic in arts and media. This paper defines the distinct staging of untamed and pristine environment in open world games as striated wilderness which is constituted by aesthetics and gazing regimes of Western culture as well as by modularity and variability of computer games as data bases. Merging the wilderness discourse with concepts of tourist gaze and prospect-refuge theory, rural open world games can be analyzed as rhythmized liminal spaces of the man-nature dichotomy. Thus, they stand in the tradition of landscape gardens and nature parks where former survival instincts and urges for exploration are experienced for recreation and entertainment. Striated wilderness has to be differentiated between place (wilderness) and practice (wildness). How do open world games regulate our understanding of landscape and longing for nature?
Insufficient muscle repair and regeneration is a major clinical issue that plagues both young patients born with congenital defects and elderly patients, such as those who have suffered a heart attack or experienced a traumatic injury resulting in volumetric muscle loss. The progression of these diseases and injuries can lead to significant complications, such as amputation, or in the case of heart muscle, progression to heart failure. Heart failure is the leading cause of death for adults in the US and one of the leading causes of death in live born infants. In both skeletal and heart muscle disease or repair, invasive surgical repair procedures result in detrimental scar tissue formation and the weakening of the surrounding muscle, limiting long-term positive patient outcomes. To correct and improve these issues, natural, bioactive, biodegradable, and implantable biomaterial systems have and are continuing to be evaluated. Current research suggests that electrical, spatial, and chemical cues are important design parameters for biomaterials with applications in striated muscle tissue regeneration. During this seminar, I will highlight recent efforts to develop a variety of materials suitable for studying fundamental concepts in striated muscle tissue engineering in vitro, as well as highlight recent efforts centered on repairing diseased cardiac tissue in vivo. To this end, we developed sponge and hydrogel-based cell-free biomaterials using silk fibroin and decellularized cardiac extracellular matrix (cECM) derived from adult or fetal porcine heart tissue. We optimized and evaluated these materials using a combination of traditional cell culture techniques and bioreactor studies in vitro and via subcutaneous implantation or application to the heart in vivo, in models of rodent myocardial infarction and porcine right ventricular outflow tract repair. For example, utilization of acellular silk-cECM sponges in the repair of myocardial infarction has led to a reduction in scar expansion and improved cardiac function in adult rats, compared to untreated controls. Results from our in vivo studies highlight the complexity of the wound healing process, which leads to alterations in tissue organization, the distribution of cells types within the tissue, and the level of vascularization. Current and future work aims to evaluate the role of the immune system in the modulation of repair and regeneration, focusing on improving biomaterial formulations through a greater understanding of cell-material interactions. Results will lead to the development of personalized biomaterials that harness the power of the immune system to promote regeneration and repair of diseased or damaged muscle tissue, emphasizing development of a natural biomaterial-based platform for surgeons aiming to meet the needs of their specific patients. Much of this work was completed in collaboration with Kelly E. Sullivan-Giachetto and Jonathan M. Grasman under the advisement of David L. Kaplan and Lauren D. Black, III, in the Biomedical Engineering Department at Tufts University during my postdoctoral studies as an NIH IRACDA Scholar. 2ff7e9595c
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