Scalable, data-assimilated models predict large-scale shoreline response to waves and sea-level rise.

Coastal change is a complex combination of multi-scale processes (e.g., wave-driven cross-shore and longshore transport; dune, bluff, and cliff erosion; overwash; fluvial and inlet sediment supply; and sea-level-driven recession).

Optimization of Xenografting Methods for Generating Human Skeletal Muscle in Mice.

Xenografts of human skeletal muscle generated in mice can be used to study muscle pathology and to test drugs designed to treat myopathies and muscular dystrophies for their efficacy and specificity in human tissue. We previously developed methods to generate mature human skeletal muscles in immunocompromised mice starting with human myogenic precursor cells (hMPCs) from healthy individuals and individuals with facioscapulohumeral muscular dystrophy (FSHD). Here, we examine a series of alternative treatments at each stage in order to optimize engraftment.

μ-Crystallin in Mouse Skeletal Muscle Promotes a Shift from Glycolytic toward Oxidative Metabolism.

μ-Crystallin, encoded by the gene, binds the thyroid hormones, T and T. Because T and T are potent regulators of metabolism and gene expression, and levels in human skeletal muscle can vary widely, we investigated the effects of overexpression of . We generated transgenic mice, tg, that expressed protein specifically in skeletal muscle at levels 2.

Keratin 18 is an integral part of the intermediate filament network in murine skeletal muscle.

Intermediate filaments (IFs) contribute to force transmission, cellular integrity, and signaling in skeletal muscle. We previously identified keratin 19 (Krt19) as a muscle IF protein. We now report the presence of a second type I muscle keratin, Krt18.

Muscle xenografts reproduce key molecular features of facioscapulohumeral muscular dystrophy.

Aberrant expression of DUX4, a gene unique to humans and primates, causes Facioscapulohumeral Muscular Dystrophy-1 (FSHD), yet the pathogenic mechanism is unknown. As transgenic overexpression models have largely failed to replicate the genetic changes seen in FSHD, many studies of endogenously expressed DUX4 have been limited to patient biopsies and myogenic cell cultures, which never fully differentiate into mature muscle fibers. We have developed a method to xenograft immortalized human muscle precursor cells from patients with FSHD and first-degree relative controls into the tibialis anterior muscle compartment of immunodeficient mice, generating human muscle xenografts.

Dynamic flood modeling essential to assess the coastal impacts of climate change.

Coastal inundation due to sea level rise (SLR) is projected to displace hundreds of millions of people worldwide over the next century, creating significant economic, humanitarian, and national-security challenges. However, the majority of previous efforts to characterize potential coastal impacts of climate change have focused primarily on long-term SLR with a static tide level, and have not comprehensively accounted for dynamic physical drivers such as tidal non-linearity, storms, short-term climate variability, erosion response and consequent flooding responses. Here we present a dynamic modeling approach that estimates climate-driven changes in flood-hazard exposure by integrating the effects of SLR, tides, waves, storms, and coastal change (i.

Effect of Ibuprofen on Skeletal Muscle of Dysferlin-Null Mice.

Ibuprofen, a nonsteroidal anti-inflammatory drug, and nitric oxide (NO) donors have been reported to reduce the severity of muscular dystrophies in mice associated with the absence of dystrophin or -sarcoglycan, but their effects on mice that are dystrophic due to the absence of dysferlin have not been examined. We have tested ibuprofen, as well as isosorbide dinitrate (ISDN), a NO donor, to learn whether used alone or together they protect dysferlin-null muscle in A/J mice from large strain injury (LSI) induced by a series of high strain lengthening contractions. Mice were maintained on chow containing ibuprofen and ISDN for 4 weeks.

Neuromuscular electrical stimulation promotes development in mice of mature human muscle from immortalized human myoblasts.

Background: Studies of the pathogenic mechanisms underlying human myopathies and muscular dystrophies often require animal models, but models of some human diseases are not yet available. Methods to promote the engraftment and development of myogenic cells from individuals with such diseases in mice would accelerate such studies and also provide a useful tool for testing therapeutics. Here, we investigate the ability of immortalized human myogenic precursor cells (hMPCs) to form mature human myofibers following implantation into the hindlimbs of non-obese diabetic-Rag1 (null) IL2rγ (null) (NOD-Rag)-immunodeficient mice.

Myopathic changes in murine skeletal muscle lacking synemin.

Diseases of striated muscle linked to intermediate filament (IF) proteins are associated with defects in the organization of the contractile apparatus and its links to costameres, which connect the sarcomeres to the cell membrane. Here we study the role in skeletal muscle of synemin, a type IV IF protein, by examining mice null for synemin (synm-null). Synm-null mice have a mild skeletal muscle phenotype.

Physiotherapy extended-role practitioner for individuals with hip and knee arthritis: patient perspectives of a rural/urban partnership.

Purpose: To explore the perspectives of people with hip and knee arthritis regarding a physiotherapy extended-role practitioner (ERP) model of care in a rural setting.

Method: Using semi-structured interviews, a qualitative descriptive case study was undertaken with 13 participants from a rural family practice located in the province of Ontario, Canada, who had all been assessed by an ERP. Transcribed interviews were analyzed for emergent themes.

Influences of desmin and keratin 19 on passive biomechanical properties of mouse skeletal muscle.

In skeletal muscle fibers, forces must be transmitted between the plasma membrane and the intracellular contractile lattice, and within this lattice between adjacent myofibrils. Based on their prevalence, biomechanical properties and localization, desmin and keratin intermediate filaments (IFs) are likely to participate in structural connectivity and force transmission. We examined the passive load-bearing response of single fibers from the extensor digitorum longus (EDL) muscles of young (3 months) and aged (10 months) wild-type, desmin-null, K19-null, and desmin/K19 double-null mice.

Unmasking potential intracellular roles for dysferlin through improved immunolabeling methods.

Mutations in the DYSF gene that severely reduce the levels of the protein dysferlin are implicated in muscle-wasting syndromes known as dysferlinopathies. Although studies of its function in skeletal muscle have focused on its potential role in repairing the plasma membrane, dysferlin has also been found, albeit inconsistently, in the sarcoplasm of muscle fibers. The aim of this article is to study the localization of dysferlin in skeletal muscle through optimized immunolabeling methods.

Daily multidisciplinary rounds to implement the ventilator bundle decreases ventilator-associated pneumonia in trauma patients: but does it affect outcome?

Background: The incidence of ventilator-associated pneumonia (VAP) in trauma patients can be decreased with use of the ventilator bundle (VAPB). Our VAP rate remained high despite the adoption of the VAPB. To better implement the VAPB, a multidisciplinary team composed of the surgical intensive care unit (SICU) nursing staff, physician, and respiratory therapist reviewed briefly a checklist of VAPB goals for each patient before morning attending rounds.

Physiology, structure, and susceptibility to injury of skeletal muscle in mice lacking keratin 19-based and desmin-based intermediate filaments.

Intermediate filaments, composed of desmin and of keratins, play important roles in linking contractile elements to each other and to the sarcolemma in striated muscle. Our previous results show that the tibialis anterior (TA) muscles of mice lacking keratin 19 (K19) lose costameres, accumulate mitochondria under the sarcolemma, and generate lower specific tension than controls. Here we compare the physiology and morphology of TA muscles of mice lacking K19 with muscles lacking desmin or both proteins [double knockout (DKO)].

Absence of keratin 19 in mice causes skeletal myopathy with mitochondrial and sarcolemmal reorganization.

Intermediate filaments, composed of desmin and of keratins, play important roles in linking contractile elements to each other and to the sarcolemma in striated muscle. We examined the contractile properties and morphology of fast-twitch skeletal muscle from mice lacking keratin 19. Tibialis anterior muscles of keratin-19-null mice showed a small but significant decrease in mean fiber diameter and in the specific force of tetanic contraction, as well as increased plasma creatine kinase levels.

Devastating consequences of subway accidents: traumatic amputations.

The efficiencies of the subway system are tempered by the occurrence of accidents, some with devastating injuries. The purpose of this study is to examine our experience with traumatic amputations after subway accidents. A retrospective trauma registry review (1989-2003) of 41 patients who presented to Bellevue Hospital, New York City, with amputations from subway accidents was undertaken to examine the following end points: age, sex, Injury Severity Score, time and mechanism of accident, history of psychiatric disorders and alcohol use, admission vital signs, Glasgow Coma Scale score, amputation type, associated injuries, limb salvage rate, operative procedures, mortality, and disposition.

Public health lessons learned from analysis of New York City subway injuries.

Serious subway injuries are devastating to their young victims and have high rates of mortality and amputation. We identified the urban population at greatest risk for subway injuries and investigated the influence of local economies on injury rates. We propose using changes in social conditions as a "trigger" for increased vigilance and protective measures at times of higher risk.

Association of small ankyrin 1 with the sarcoplasmic reticulum.

Small ankyrin 1, or sAnk1, is a small, alternatively spliced product of the erythroid ankyrin gene, ANK1, that is expressed in striated muscle and concentrated in the network sarcoplasmic reticulum (SR) surrounding the Z disks and M lines. We have characterized sAnk1 in muscle homogenates and SR vesicles, and have identified the region that targets it to the network SR. Selective extractions and partitioning into Triton X-114 show that sAnk1 behaves like the SR Ca-ATPase and so is an integral protein of the SR membrane.

Specific interaction of the actin-binding domain of dystrophin with intermediate filaments containing keratin 19.

Cytokeratins 8 and 19 concentrate at costameres of striated muscle and copurify with the dystrophin-glycoprotein complex, perhaps through the interaction of the cytokeratins with the actin-binding domain of dystrophin. We overexpressed dystrophin's actin-binding domain (Dys-ABD), K8 and K19, as well as closely related proteins, in COS-7 cells to assess the basis and specificity of their interaction. Dys-ABD alone associated with actin microfilaments.

Cloning and characterization of cytokeratins 8 and 19 in adult rat striated muscle. Interaction with the dystrophin glycoprotein complex.

We used degenerate primers for the amino- and carboxyl-terminal ends of the rod domains of intermediate filament proteins in reverse transcriptase-PCR experiments to identify and clone cytokeratins 8 and 19 (K8 and K19) from cardiac muscle of the adult rat. Northern blots showed that K8 has a 2.2-kb transcript and K19 has a 1.

Plasma membrane-cytoskeleton-endoplasmic reticulum complexes in neurons and astrocytes.

The possibility that certain integral plasma membrane (PM) proteins involved in Ca(2+) homeostasis form junctional units with adjacent endoplasmic reticulum (ER) in neurons and glia was explored using immunoprecipitation and immunocytochemistry. Rat brain membranes were solubilized with the mild, non-ionic detergent, IGEPAL CA-630. Na(+)/Ca(2+) exchanger type 1 (NCX1), a key PM Ca(2+) transporter, was immunoprecipitated from the detergent-soluble fraction.

Costameres: repeating structures at the sarcolemma of skeletal muscle.

Costameres, structures at the plasma membrane of skeletal muscle, are present in a rectilinear array that parallels the organization of the underlying contractile apparatus. Costameres have three major functions: to keep the plasma membrane, or sarcolemma, aligned and in register with nearby contractile structures; to protect the sarcolemma against contraction-induced damage; and to transmit some of the forces of contraction laterally, to the extracellular matrix. These functions require that costameres link the contractile apparatus through the membrane to the extracellular matrix.

Sarcolemmal organization in skeletal muscle lacking desmin: evidence for cytokeratins associated with the membrane skeleton at costameres.

The sarcolemma of fast-twitch muscle is organized into "costameres," structures that are oriented transversely, over the Z and M lines of nearby myofibrils, and longitudinally, to form a rectilinear lattice. Here we examine the role of desmin, the major intermediate filament protein of muscle in organizing costameres. In control mouse muscle, desmin is enriched at the sarcolemmal domains that lie over nearby Z lines and that also contain beta-spectrin.