More than a bystander: the contributions of intrinsic skeletal muscle defects in motor neuron diseases

PubMed Central

Boyer, Justin G.; Ferrier, Andrew; Kothary, Rashmi

2013-01-01

Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and spinal-bulbar muscular atrophy (SBMA) are devastating diseases characterized by the degeneration of motor neurons. Although the molecular causes underlying these diseases differ, recent findings have highlighted the contribution of intrinsic skeletal muscle defects in motor neuron diseases. The use of cell culture and animal models has led to the important finding that muscle defects occur prior to and independently of motor neuron degeneration in motor neuron diseases. In SMA for instance, the muscle specific requirements of the SMA disease-causing gene have been demonstrated by a series of genetic rescue experiments in SMA models. Conditional ALS mouse models expressing a muscle specific mutant SOD1 gene develop atrophy and muscle degeneration in the absence of motor neuron pathology. Treating SBMA mice by over-expressing IGF-1 in a skeletal muscle-specific manner attenuates disease severity and improves motor neuron pathology. In the present review, we provide an in depth description of muscle intrinsic defects, and discuss how they impact muscle function in these diseases. Furthermore, we discuss muscle-specific therapeutic strategies used to treat animal models of SMA, ALS, and SBMA. The study of intrinsic skeletal muscle defects is crucial for the understanding of the pathophysiology of these diseases and will open new therapeutic options for the treatment of motor neuron diseases. PMID:24391590

Reconstruction of upper lip muscle system by anatomy, magnetic resonance imaging, and serial histological sections.

PubMed

Bo, Chen; Ningbei, Yin

2014-01-01

Surgeons need references to undertake cleft lip repairs. We aimed to establish a three-dimensional model of upper lip muscles. We examined specimens from 2 adult cadaver heads and 8 adult cadaver lips, obtaining serial sections in the axial, sagittal, and coronal planes. Sections were stained to observe the philtrum, Cupid bow, vermilion, and nostril sill. Reconstruction was done with three-dimensional software (eg, 3D-DOCTOR, MicroMR). Parallel circular muscle fibers existed between modioli. The orbicularis oris deep layer contained fan muscle fibers inclining inward. Some ended at the anterior nasal crest. Others migrated to the depressor septum, crossed the midline, and migrated to the nasalis muscle. At the nostril floor, the depressor septum muscle bundle and ipsilateral orbicularis oris overlapped the nasalis muscle and the contralateral orbicularis oris. This construction shaped the nostril sill. The levator labii superioris alaeque nasi, levator labii superioris, and zygomaticus minor crossed the nasolabial groove and migrated to the superficial orbicularis oris, entering the outer edge of the nasal alar to the upper lip near the vermilion border and philtrum ridge, shaping Cupid bow. Contralateral deep orbicularis oris muscle fibers crossed the philtrum dimple to the lateral philtrum ridge (axial plane). Superficial reticular muscle fibers of the levator labii superioris, zygomaticus minor, zygomaticus major, and orbicularis oris inserted into the medial philtrum ridge (coronal plane). They intersected to form the philtrum ridge. A three-dimensional upper lip muscular system model was established that can be referenced for cleft lip repair and lip operations.

Inequities in exposure to occupational risk factors between Māori and non-Māori workers in Aotearoa New Zealand.

PubMed

Denison, Hayley J; Eng, Amanda; Barnes, Lucy A; Cheng, Soo; 't Mannetje, Andrea; Haddock, Katharine; Douwes, Jeroen; Pearce, Neil; Ellison-Loschmann, Lis

2018-05-02

Health inequities between indigenous and non-indigenous people are well documented. However, the contribution of differential exposure to risk factors in the occupational environment remains unclear. This study assessed differences in the prevalence of self-reported exposure to disease risk factors, including dust and chemicals, physical factors and organisational factors, between Māori and non-Māori workers in New Zealand. Potential participants were sampled from the New Zealand electoral rolls and invited to take part in a telephone interview, which included questions about current workplace exposures. Logistic regression, accounting for differences in age, socioeconomic status and occupational distribution between Māori and non-Māori, was used to assess differences in exposures. In total, 2344 Māori and 2710 non-Māori participants were included in the analyses. Māori had greater exposure to occupational risk factors than non-Māori. For dust and chemical exposures, the main differences related to Māori working in occupations where these exposures are more common. However, even within the same job, Māori were more likely to be exposed to physical factors such as heavy lifting and loud noise, and organisational factors such as carrying out repetitive tasks and working to tight deadlines compared with non-Māori. This is one of the first studies internationally to compare occupational risk factors between indigenous and non-indigenous people. These findings suggest that the contribution of the occupational environment to health inequities between Māori and non-Māori has been underestimated and that work tasks may be unequally distributed according to ethnicity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Enhancing Māori food security using traditional kai.

PubMed

McKerchar, Christina; Bowers, Sharron; Heta, Craig; Signal, Louise; Matoe, Leonie

2015-09-01

Lack of food security is one of the major nutrition issues facing Māori today. Loss of traditional kai (food) gathering places and practices following colonisation and urbanisation has impacted negatively on food security for Māori. This paper explores the role of Māori in enhancing Māori food security through revitalising traditional kai. A narrative literature review of peer reviewed and grey literature on revitalising traditional kai for Māori was conducted. The focus was on two areas: increasing the availability of traditional kai to Māori households (such as through replenishing fish stocks, and gardening projects) and increasing the financial means available to Māori households to purchase food (by economic development of traditional kai industries and employment creation). A range of activities to improve food security for Māori by revitalising traditional kai was identified in the literature. Māori are now significant players in New Zealand's fishing industry, and are developing their horticultural resources. Gardening initiatives have also grown considerably in Māori communities. Enabling factors included: the return of traditional kai resources by the Crown, and successful pursuit by Māori of the legal rights to develop them; development of Māori models of governance; government policy around Māori economic development and healthy eating; and Māori leadership on the issue. Barriers to revitalising traditional kai that remain to be addressed include: tensions between Government and Māori goals and models of resource management; economic pressures resulting in severely depleted fishing stocks; and pollution of marine and freshwater fish. Revitalising traditional kai has considerable potential to improve food security for Māori, both directly in terms of food supply and by providing income, and warrants policy and practical support. These findings have implications for other indigenous cultures who are struggling to be food secure. © The

Probing the origin of UX Ori-type variability in the YSO binary CO Ori with VLTI/GRAVITY

NASA Astrophysics Data System (ADS)

Davies, C. L.; Kreplin, A.; Kluska, J.; Hone, E.; Kraus, S.

2018-03-01

The primary star in the young stellar object binary CO Ori displays UX Ori-type variability: irregular, high amplitude optical, and near-infrared photometric fluctuations where flux minima coincide with polarization maxima. This is attributed to changes in local opacity. In CO Ori A, these variations exhibit a 12.4 yr cycle. Here, we investigate the physical origin of the fluctuating opacity and its periodicity using interferometric observations of CO Ori obtained using VLTI/GRAVITY. Continuum K-band circum-primary and circum-secondary emission are marginally spatially resolved for the first time, while Brγ emission is detected in the spectrum of the secondary. We estimate a spectral type range for CO Ori B of K2-K5 assuming visual extinction, AV = 2 and a distance of 430 pc. From geometric modelling of the continuum visibilities, the circum-primary emission is consistent with a central point source plus a Gaussian component with a full width at half-maximum of 2.31 ± 0.04 mas, inclined at 30.2° ± 2.2° and with a major axis position angle of 40° ± 6°. This inclination is lower than that reported for the discs of other UX Ori-type stars, providing a first indication that the UX Ori phenomena may arise through fluctuations in circum-stellar material exterior to a disc, for example, in a dusty outflow. An additional wide, symmetric Gaussian component is required to fit the visibilities of CO Ori B, signifying a contribution from scattered light. Finally, closure phases of CO Ori A were used to investigate whether the 12.4 yr periodicity is associated with an undetected third component, as has been previously suggested. We rule out any additional companions contributing more than 3.6 per cent to the K-band flux within ˜7.3-20 mas of CO Ori A.

Experience with peroneus brevis muscle flaps for reconstruction of distal leg and ankle defects

PubMed Central

Bajantri, Babu; Bharathi, Ravindra; Ramkumar, Sanjai; Latheef, Latheesh; Dhane, Smitha; Sabapathy, S. Raja

2013-01-01

Objective: Peroneus brevis is a muscle in the leg which is expendable without much functional deficit. The objective of this study was to find out its usefulness in coverage of the defects of the lower leg and ankle. Patients and Methods: A retrospective analysis of the use of 39 pedicled peroneus brevis muscle flaps used for coverage of defects of the lower leg and ankle between November 2010 and December 2012 was carried out. The flaps were proximally based for defects of the lower third of the leg in 12 patients and distally based for reconstruction of defects of the ankle in 26 patients, with one patient having flaps on both ankles. Results: Partial flap loss in critical areas was found in four patients requiring further flap cover and in non-critical areas in two patients, which were managed with a skin graft. Three of the four critical losses occurred when we used it for covering defects over the medial malleolus. There was no complete flap loss in any of the patients. Conclusion: This flap has a unique vascular pattern and fails to fit into the classification of the vasculature of muscles by Mathes and Nahai. The unusual feature is an axial vessel system running down the deep aspect of the muscle and linking the perforators from the peroneal artery and anterior tibial artery, which allows it to be raised proximally or distally on a single perforator. The flap is simple to raise and safe for the reconstruction of small-to moderate-sized skin defects of the distal third of the tibia and all parts of the ankle except the medial malleolus, which is too far from the pedicle of the distally based flap. The donor site can be closed primarily to provide a linear scar. The muscle flap thins with time to provide a good result aesthetically at the primary defect. PMID:23960305

Varicella-zoster virus (VZV) origin of DNA replication oriS influences origin-dependent DNA replication and flanking gene transcription.

PubMed

Khalil, Mohamed I; Sommer, Marvin H; Hay, John; Ruyechan, William T; Arvin, Ann M

2015-07-01

The VZV genome has two origins of DNA replication (oriS), each of which consists of an AT-rich sequence and three origin binding protein (OBP) sites called Box A, C and B. In these experiments, the mutation in the core sequence CGC of the Box A and C not only inhibited DNA replication but also inhibited both ORF62 and ORF63 expression in reporter gene assays. In contrast the Box B mutation did not influence DNA replication or flanking gene transcription. These results suggest that efficient DNA replication enhances ORF62 and ORF63 transcription. Recombinant viruses carrying these mutations in both sites and one with a deletion of the whole oriS were constructed. Surprisingly, the recombinant virus lacking both copies of oriS retained the capacity to replicate in melanoma and HELF cells suggesting that VZV has another origin of DNA replication. Copyright © 2015 Elsevier Inc. All rights reserved.

Vitamin D status of Māori and non-Māori octogenarians in New Zealand: a Cohort Study (LiLACS NZ).

PubMed

Bacon, Catherine J; Kerse, Ngaire; Hayman, Karen J; Moyes, Simon A; Teh, Ruth O; Kepa, Mere; Pillai, Avinesh; Dyall, Lorna

2016-12-01

This study assessed vitamin D status and its determinants in a cohort of octogenarians living within New Zealand's Bay of Plenty and Lakes Districts. Serum 25- hydroxyvitamin D [25(OH)D] concentration was measured in 209 Māori (aged 80-90 years) and 357 non-Māori (85 years), along with demographic, lifestyle, supplement use and other health data. Mean [95% CI] 25(OH)D concentration was 69 [67 to 72] nmol/L, with 15% >100 nmol/L and 6 individuals >150 nmol/L. Concentrations in Māori (59 [55 to 62] 4 nmol/L) were lower than in non-Māori (75 [72 to 78] nmol/L; p<0.001), a difference maintained when adjusted for day-of-year measured. Vitamin D supplementation was reported by 98 participants (18%): including a greater proportion of women (24%) than men (11%; p<0.001) and of non-Māori (24%) than Māori (7%; p<0.001). Of those taking vitamin D, 49% took high oral doses (>=25 μg/day or equivalent) and five individuals took >50 μg/day. Vitamin D supplement use strongly and independently predicted seasonally- adjusted 25(OH)D concentration and was associated with 28 nmol/L higher levels than non-use. Other predictors included Māori ethnicity (10 nmol/L lower concentration than for non-Māori), and female gender (11 nmol/L lower). Vitamin D status in New Zealand octogenarians appears higher than previously reported, particularly in non-Māori compared to Māori. Prescribed and non-prescribed oral vitamin D supplementation is prevalent in this group and a strong indicator of vitamin D status.

Quantitative evaluation of skeletal muscle defects in second harmonic generation images.

PubMed

Liu, Wenhua; Raben, Nina; Ralston, Evelyn

2013-02-01

Skeletal muscle pathologies cause irregularities in the normally periodic organization of the myofibrils. Objective grading of muscle morphology is necessary to assess muscle health, compare biopsies, and evaluate treatments and the evolution of disease. To facilitate such quantitation, we have developed a fast, sensitive, automatic imaging analysis software. It detects major and minor morphological changes by combining texture features and Fourier transform (FT) techniques. We apply this tool to second harmonic generation (SHG) images of muscle fibers which visualize the repeating myosin bands. Texture features are then calculated by using a Haralick gray-level cooccurrence matrix in MATLAB. Two scores are retrieved from the texture correlation plot by using FT and curve-fitting methods. The sensitivity of the technique was tested on SHG images of human adult and infant muscle biopsies and of mouse muscle samples. The scores are strongly correlated to muscle fiber condition. We named the software MARS (muscle assessment and rating scores). It is executed automatically and is highly sensitive even to subtle defects. We propose MARS as a powerful and unbiased tool to assess muscle health.

Quantitative evaluation of skeletal muscle defects in second harmonic generation images

NASA Astrophysics Data System (ADS)

Liu, Wenhua; Raben, Nina; Ralston, Evelyn

2013-02-01

Skeletal muscle pathologies cause irregularities in the normally periodic organization of the myofibrils. Objective grading of muscle morphology is necessary to assess muscle health, compare biopsies, and evaluate treatments and the evolution of disease. To facilitate such quantitation, we have developed a fast, sensitive, automatic imaging analysis software. It detects major and minor morphological changes by combining texture features and Fourier transform (FT) techniques. We apply this tool to second harmonic generation (SHG) images of muscle fibers which visualize the repeating myosin bands. Texture features are then calculated by using a Haralick gray-level cooccurrence matrix in MATLAB. Two scores are retrieved from the texture correlation plot by using FT and curve-fitting methods. The sensitivity of the technique was tested on SHG images of human adult and infant muscle biopsies and of mouse muscle samples. The scores are strongly correlated to muscle fiber condition. We named the software MARS (muscle assessment and rating scores). It is executed automatically and is highly sensitive even to subtle defects. We propose MARS as a powerful and unbiased tool to assess muscle health.

Biotechnology: the language of multiple views in Māori communities.

PubMed

Te Momo, O H Fiona

2007-09-01

In Aotearoa (New Zealand), the government funded studies on communicating biotechnology to different sectors in the community from 2003 to 2006. Subsequently, a researcher covering the Māori sector performed a content analysis of data gathered in the community. Qualitative analysis methods included examining text from participant interviews, focus groups, government documents, newspapers, Internet sites, and current literature. Content was coded by identifying common themes in the English and the Māori language. Words like genetic modification (GM), genetic engineering (GE), and biotechnology were explained to provide a basic understanding between the communities and researcher. The terminology applied in the research was essential to achieve communication between the researcher and the community. The resultant themes represented seven views to interpret the communities association with biotechnology: purist Māori, religious Māori, anti Māori, pro Māori, no Māori, uncertain Māori, and middle Māori views. The themes are taken from the analysis of data compiled after 3 years of completing different stages of a research project. The views indicate that a common understanding can be achieved in the diverse range of Māori tribal communities providing those communicating biotechnology can identify the view and interpretations communities associate with biotechnology. This knowledge is essential for government agencies, researchers, community practitioners, scientist, and businesses that desire to dialogue with Māori communities in the language of biotechnology.

Regions flanking ori sequences affect the replication efficiency of the mitochondrial genome of ori+ petite mutants from yeast.

PubMed

Rayko, E; Goursot, R; Cherif-Zahar, B; Melis, R; Bernardi, G

1988-03-31

The mitochondrial genomes of progenies from 26 crosses between 17 cytoplasmic, spontaneous, suppressive, ori+ petite mutants of Saccharomyces cerevisiae have been studied by electrophoresis of restriction fragments. Only parental genomes (or occasionally, genomes derived from them by secondary excisions) were found in the progenies of the almost 500 diploids investigated; no evidence for illegitimate, site-specific mitochondrial recombination was detected. One of the parental genomes was always found to be predominate over the other one, although to different extents in different crosses. This predominance appears to be due to a higher replication efficiency, which is correlated with a greater density of ori sequences on the mitochondrial genome (and with a shorter repeat unit size of the latter). Exceptions to the 'repeat-unit-size rule' were found, however, even when the parental mitochondrial genomes carried the same ori sequence. This indicates that noncoding, intergenic sequences outside ori sequences also play a role in modulating replication efficiency. Since in different petites such sequences differ in primary structure, size, and position relative to ori sequences, this modulation is likely to take place through an indirect effect on DNA and nucleoid structure.

Radiological Assessment of Bioengineered Bone in a Muscle Flap for the Reconstruction of Critical-Size Mandibular Defect

PubMed Central

Al-Fotawei, Randa; Ayoub, Ashraf F.; Heath, Neil; Naudi, Kurt B.; Tanner, K. Elizabeth; Dalby, Matthew J.; McMahon, Jeremy

2014-01-01

This study presents a comprehensive radiographic evaluation of bone regeneration within a pedicled muscle flap for the reconstruction of critical size mandibular defect. The surgical defect (20 mm×15 mm) was created in the mandible of ten experimental rabbits. The masseter muscle was adapted to fill the surgical defect, a combination of calcium sulphate/hydroxyapatite cement (CERAMENT™ |SPINE SUPPORT), BMP-7 and rabbit mesenchymal stromal cells (rMSCs) was injected inside the muscle tissue. Radiographic assessment was carried out on the day of surgery and at 4, 8, and 12 weeks postoperatively. At 12 weeks, the animals were sacrificed and cone beam computerized tomography (CBCT) scanning and micro-computed tomography (µ-CT) were carried out. Clinically, a clear layer of bone tissue was identified closely adherent to the border of the surgical defect. Sporadic radio-opaque areas within the surgical defect were detected radiographically. In comparison with the opposite non operated control side, the estimated quantitative scoring of the radio-opacity was 46.6% ±15, the mean volume of the radio-opaque areas was 63.4% ±20. Areas of a bone density higher than that of the mandibular bone (+35% ±25%) were detected at the borders of the surgical defect. The micro-CT analysis revealed thinner trabeculae of the regenerated bone with a more condensed trabecular pattern than the surrounding native bone. These findings suggest a rapid deposition rate of the mineralised tissue and an active remodelling process of the newly regenerated bone within the muscle flap. The novel surgical model of this study has potential clinical application; the assessment of bone regeneration using the presented radiolographic protocol is descriptive and comprehensive. The findings of this research confirm the remarkable potential of local muscle flaps as local bioreactors to induce bone formation for reconstruction of maxillofacial bony defects. PMID:25226170

Rapid and reliable healing of critical size bone defects with genetically modified sheep muscle.

PubMed

Liu, F; Ferreira, E; Porter, R M; Glatt, V; Schinhan, M; Shen, Z; Randolph, M A; Kirker-Head, C A; Wehling, C; Vrahas, M S; Evans, C H; Wells, J W

2015-09-21

Large segmental defects in bone fail to heal and remain a clinical problem. Muscle is highly osteogenic, and preliminary data suggest that autologous muscle tissue expressing bone morphogenetic protein-2 (BMP-2) efficiently heals critical size defects in rats. Translation into possible human clinical trials requires, inter alia, demonstration of efficacy in a large animal, such as the sheep. Scale-up is fraught with numerous biological, anatomical, mechanical and structural variables, which cannot be addressed systematically because of cost and other practical issues. For this reason, we developed a translational model enabling us to isolate the biological question of whether sheep muscle, transduced with adenovirus expressing BMP-2, could heal critical size defects in vivo. Initial experiments in athymic rats noted strong healing in only about one-third of animals because of unexpected immune responses to sheep antigens. For this reason, subsequent experiments were performed with Fischer rats under transient immunosuppression. Such experiments confirmed remarkably rapid and reliable healing of the defects in all rats, with bridging by 2 weeks and remodelling as early as 3-4 weeks, despite BMP-2 production only in nanogram quantities and persisting for only 1-3 weeks. By 8 weeks the healed defects contained well-organised new bone with advanced neo-cortication and abundant marrow. Bone mineral content and mechanical strength were close to normal values. These data demonstrate the utility of this model when adapting this technology for bone healing in sheep, as a prelude to human clinical trials.

oRis: multiagents approach for image processing

NASA Astrophysics Data System (ADS)

Rodin, Vincent; Harrouet, Fabrice; Ballet, Pascal; Tisseau, Jacques

1998-09-01

In this article, we present a parallel image processing system based on the concept of reactive agents. This means that, in our system, each agent has a very simple behavior which allows it to take a decision (find out an edge, a region, ...) according to its position in the image and to the information enclosed in it. Our system lies in the oRis language, which allows to describe very finely and simply the agents' behaviors. In fact, oRis is an interpreted and dynamic multiagent language. First of all, oRis is an object language with the use of classes regrouping attributes and methods. The syntax is close to the C++ language and includes notions of multiple inheritance, oRis is also an agent language: every object with a method `main()' becomes an agent. This method is cyclically executed by the system scheduler and corresponds to the agent behavior. We also present an application made with oRis. This application allows to detect concentric striae located on different natural `objects' (age-rings of tree, fish otolith growth rings, striae of some minerals, ...). The stopping of the multiagent system is implemented through a technique issued from immunology: the apoptosis.

Anatomic variations found on dissection of depressor septi nasi muscles in cadavers.

PubMed

Ebrahimi, Ali; Nejadsarvari, Nasrin; Motamedi, Mohammad Hosein Kalantar; Rezaee, Maryam; Koushki, Ehsan Shams

2012-01-01

To define variations of the depressor septi muscle in Iranians; to provide guidance for modification of this muscle during rhinoplasty in patients with an active muscle and short upper lip; and to correlate our findings with our clinical experience to develop the applied algorithms. This study was conducted by dissecting 82 depressor septi nasi muscles in 41 Iranian cadavers. Origin and insertion points of each muscle were studied. Three variations were found in muscle insertion points: periosteal, orbicularis oris, and floating. Forty-four percent of the muscles were inserted into the periosteum of the maxilla (n = 36); 39% of muscles were inserted into the orbicularis oris muscle (n = 32); and 17% were diminutive or floating (n = 14). Periosteal insertion was thicker and stronger than the other variations. In all cadavers, the origin of the muscle was medial crus of alar cartilage and caudal of the nasal septum. This cadaveric dissection showed that the percentage of depressor septi muscle insertions is not similar to that found in other surveys. In this study, periosteal insertion of the depressor septi muscle was the most common variation.

Defect in skeletal muscle phosphatidylinositol-3-kinase in obese insulin-resistant mice.

PubMed Central

Heydrick, S J; Jullien, D; Gautier, N; Tanti, J F; Giorgetti, S; Van Obberghen, E; Le Marchand-Brustel, Y

1993-01-01

Activation of phosphatidylinositol-3-kinase (PI3K) is one of the earliest postreceptor events in the insulin signaling pathway. Incubation of soleus muscles from lean mice with 50 nM insulin caused a 3-10-fold increase in antiphosphotyrosine-immunoprecipitable PI3K (antiPTyr-PI3K) activity within 2 min in muscle homogenates as well as both the cytosolic and membrane fractions. Insulin did not affect total PI3K activity. Both the antiPTyr-PI3K stimulation and activation of insulin receptor tyrosine kinase were dependent on hormone concentration. In muscles from obese, insulin-resistant mice, there was a 40-60% decrease in antiPTyr-PI3K activity after 2 min of insulin that was present equally in the cytosolic and membrane fractions. A significant reduction in insulin sensitivity was also observed. The defect appears to result from alterations in both insulin receptor and postreceptor signaling. Starvation of obese mice for 48 h, which is known to reverse insulin resistance, normalized the insulin response of both PI3K and the receptor tyrosine kinase. The results demonstrate that: (a) antiPTyr-PI3K activity is responsive to insulin in mouse skeletal muscle, (b) both the insulin responsiveness and sensitivity of this activity are blunted in insulin-resistant muscles from obese mice, (c) these alterations result from a combination of insulin receptor and postreceptor defects, and (d) starvation restores normal insulin responses. Images PMID:8386184

Retrofitting BACs with G418 resistance, luciferase, and oriP and EBNA-1 – new vectors for in vitro and in vivo delivery

PubMed Central

Magin-Lachmann, Christine; Kotzamanis, George; D'Aiuto, Leonardo; Wagner, Ernst; Huxley, Clare

2003-01-01

Background Bacterial artificial chromosomes (BACs) have been used extensively for sequencing the human and mouse genomes and are thus readily available for most genes. The large size of BACs means that they can generally carry intact genes with all the long range controlling elements that drive full levels of tissue-specific expression. For gene expression studies and gene therapy applications it is useful to be able to retrofit the BACs with selectable genes such as G418 resistance, reporter genes such as luciferase, and oriP/EBNA-1 from Epstein Barr virus which allows long term episomal maintenance in mammalian cells. Results We describe a series of retrofitting plasmids and a protocol for in vivo loxP/Cre recombination. The vector pRetroNeo carries a G418 resistance cassette, pRetroNeoLuc carries G418 resistance and a luciferase expression cassette, pRetroNeoLucOE carries G418 resistance, luciferase and an oriP/EBNA-1 cassette and pRetroNeoOE carries G418 resistance and oriP/EBNA-1. These vectors can be efficiently retrofitted onto BACs without rearrangement of the BAC clone. The luciferase cassette is expressed efficiently from the retrofitting plasmids and from retrofitted BACs after transient transfection of B16F10 cells in tissue culture and after electroporation into muscles of BALB/c mice in vivo. We also show that a BAC carrying GFP, oriP and EBNA-1 can be transfected into B16F10 cells with Lipofectamine 2000 and can be rescued intact after 5 weeks. Conclusion The pRetro vectors allow efficient retrofitting of BACs with G418 resistance, luciferase and/or oriP/EBNA-1 using in vivo expression of Cre. The luciferase reporter gene is expressed after transient transfection of retrofitted BACs into cells in tissue culture and after electroporation into mouse muscle in vivo. OriP/EBNA-1 allows stable maintenance of a 150-kb BAC without rearrangement for at least 5 weeks. PMID:12609052

42 CFR 93.402 - ORI allegation assessments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... RESEARCH MISCONDUCT Responsibilities of the U.S. Department of Health and Human Services Research Misconduct Issues § 93.402 ORI allegation assessments. (a) When ORI receives an allegation of research misconduct directly or becomes aware of an allegation or apparent instance of research misconduct, it may...

A Disulfide Bond-forming Machine Is Linked to the Sortase-mediated Pilus Assembly Pathway in the Gram-positive Bacterium Actinomyces oris.

PubMed

Reardon-Robinson, Melissa E; Osipiuk, Jerzy; Chang, Chungyu; Wu, Chenggang; Jooya, Neda; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

2015-08-28

Export of cell surface pilins in Gram-positive bacteria likely occurs by the translocation of unfolded precursor polypeptides; however, how the unfolded pilins gain their native conformation is presently unknown. Here, we present physiological studies to demonstrate that the FimA pilin of Actinomyces oris contains two disulfide bonds. Alanine substitution of cysteine residues forming the C-terminal disulfide bridge abrogates pilus assembly, in turn eliminating biofilm formation and polymicrobial interaction. Transposon mutagenesis of A. oris yielded a mutant defective in adherence to Streptococcus oralis, and revealed the essential role of a vitamin K epoxide reductase (VKOR) gene in pilus assembly. Targeted deletion of vkor results in the same defects, which are rescued by ectopic expression of VKOR, but not a mutant containing an alanine substitution in its conserved CXXC motif. Depletion of mdbA, which encodes a membrane-bound thiol-disulfide oxidoreductase, abrogates pilus assembly and alters cell morphology. Remarkably, overexpression of MdbA or a counterpart from Corynebacterium diphtheriae, rescues the Δvkor mutant. By alkylation assays, we demonstrate that VKOR is required for MdbA reoxidation. Furthermore, crystallographic studies reveal that A. oris MdbA harbors a thioredoxin-like fold with the conserved CXXC active site. Consistently, each MdbA enzyme catalyzes proper disulfide bond formation within FimA in vitro that requires the catalytic CXXC motif. Because the majority of signal peptide-containing proteins encoded by A. oris possess multiple Cys residues, we propose that MdbA and VKOR constitute a major folding machine for the secretome of this organism. This oxidative protein folding pathway may be a common feature in Actinobacteria. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A Disulfide Bond-forming Machine Is Linked to the Sortase-mediated Pilus Assembly Pathway in the Gram-positive Bacterium Actinomyces oris*

PubMed Central

Reardon-Robinson, Melissa E.; Osipiuk, Jerzy; Chang, Chungyu; Wu, Chenggang; Jooya, Neda; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

2015-01-01

Export of cell surface pilins in Gram-positive bacteria likely occurs by the translocation of unfolded precursor polypeptides; however, how the unfolded pilins gain their native conformation is presently unknown. Here, we present physiological studies to demonstrate that the FimA pilin of Actinomyces oris contains two disulfide bonds. Alanine substitution of cysteine residues forming the C-terminal disulfide bridge abrogates pilus assembly, in turn eliminating biofilm formation and polymicrobial interaction. Transposon mutagenesis of A. oris yielded a mutant defective in adherence to Streptococcus oralis, and revealed the essential role of a vitamin K epoxide reductase (VKOR) gene in pilus assembly. Targeted deletion of vkor results in the same defects, which are rescued by ectopic expression of VKOR, but not a mutant containing an alanine substitution in its conserved CXXC motif. Depletion of mdbA, which encodes a membrane-bound thiol-disulfide oxidoreductase, abrogates pilus assembly and alters cell morphology. Remarkably, overexpression of MdbA or a counterpart from Corynebacterium diphtheriae, rescues the Δvkor mutant. By alkylation assays, we demonstrate that VKOR is required for MdbA reoxidation. Furthermore, crystallographic studies reveal that A. oris MdbA harbors a thioredoxin-like fold with the conserved CXXC active site. Consistently, each MdbA enzyme catalyzes proper disulfide bond formation within FimA in vitro that requires the catalytic CXXC motif. Because the majority of signal peptide-containing proteins encoded by A. oris possess multiple Cys residues, we propose that MdbA and VKOR constitute a major folding machine for the secretome of this organism. This oxidative protein folding pathway may be a common feature in Actinobacteria. PMID:26170452

Patterns of privilege: A total cohort analysis of admission and academic outcomes for Māori, Pacific and non-Māori non-Pacific health professional students.

PubMed

Wikaire, Erena; Curtis, Elana; Cormack, Donna; Jiang, Yannan; McMillan, Louise; Loto, Rob; Reid, Papaarangi

2016-10-07

Tertiary institutions are struggling to ensure equitable academic outcomes for indigenous and ethnic minority students in health professional study. This demonstrates disadvantaging of ethnic minority student groups (whereby Indigenous and ethnic minority students consistently achieve academic outcomes at a lower level when compared to non-ethnic minority students) whilst privileging non-ethnic minority students and has important implications for health workforce and health equity priorities. Understanding the reasons for academic inequities is important to improve institutional performance. This study explores factors that impact on academic success for health professional students by ethnic group. Kaupapa Māori methodology was used to analyse data for 2686 health professional students at the University of Auckland in 2002-2012. Data were summarised for admission variables: school decile, Rank Score, subject credits, Auckland school, type of admission, and bridging programme; and academic outcomes: first-year grade point average (GPA), first-year passed all courses, year 2 - 4 programme GPA, graduated, graduated in the minimum time, and composite completion for Māori, Pacific, and non-Māori non-Pacific (nMnP) students. Statistical tests were used to identify significant differences between the three ethnic groupings. Māori and Pacific students were more likely to attend low decile schools (27 % Māori, 33 % Pacific vs. 5 % nMnP, p < 0.01); complete bridging foundation programmes (43 % Māori, 50 % Pacific vs. 5 % nMnP, p < 0.01), and received lower secondary school results (Rank Score 197 Māori, 178 Pacific vs. 231 nMnP, p < 0.01) when compared with nMnP students. Patterns of privilege were seen across all academic outcomes, whereby nMnP students achieved higher first year GPA (3.6 Māori, 2.8 Pacific vs. 4.7 nMnP, p < 0.01); were more likely to pass all first year courses (61 % Māori, 41 % Pacific vs. 78 % nMnP, p < 0.01); to

Reconstruction of Knee Defects Using Pedicled Gastrocnemius Muscle Flap with Split-Thickness Skin Grafting: A Single Surgeon's Experience with 21 Patients.

PubMed

Kilic, Ali; Denney, Brad; de la Torre, Jorge

2018-05-31

Generally, reconstruction of knee defects with exposed bone, joint, tendon, and/or hardware requires a vascularized muscle flap for coverage. Although there are several surgical options for a knee defect reconstruction, the pedicled gastrocnemius muscle still remains the workhorse flap. Although this flap is commonly used for knee defect reconstruction and the technique is described very well, there is an absence of information in the literature detailing the technique of harvesting and insetting of the gastrocnemius flap step by step with illustrations. The purpose of this article is to describe in detail the technique to reconstruct defects of the knee with pedicled gastrocnemius muscle flap as well as to present demographics and surgical results of 21 patients who had knee reconstruction with a pedicled gastrocnemius muscle flap and split-thickness skin grafting. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Detailed Anatomy of the Nasolabial Muscle in Human Fetuses as Determined by Micro-CT Combined With Iodine Staining.

PubMed

Wu, Jiajun; Yin, Ningbei

2016-01-01

This study aims to investigate the 3-dimensional (3D) anatomical structure of the orbicularis oris and nasalis, which are closely associated with the appearance of the upper lip and lower part of the nose. The relationship of the complicated 3D anatomical structure with the outline shape was also determined. Microcomputed tomography combined with iodine staining was used to scan the nasolabial tissues of 3 aborted fetuses. The strictly aligned, corrected, full-capacity, 2-dimensional (2D) grayscale images obtained were then used to reconstruct 3D structures using a 3D reconstruction software. 2D grayscale slices and a 3D anatomical model of the orbicularis oris and nasalis of the specimens were obtained. The 2D images and the 3D model confirmed the orbicularis oris anatomical structure reported in previous studies and also provided new insights (such as the close association of the formation of the philtral dimple, lip peak, philtral ridge, and nasal sill with the orbicularis oris). In addition, the results show that the nasolabial muscle consists of muscle fibers from different sources and is divided into four distinct parts: pars marginalis, pars peripheralis, muscle fibers of the levator labii superioris, and nasalis muscle fibers. The 3D anatomical structures indicate that the orbicularis oris and nasalis are closely associated with the appearances of the upper lip and lower part of the nose. The results may aid plastic surgeons in performing cleft-lip correction surgery.

Electron Transport Chain Is Biochemically Linked to Pilus Assembly Required for Polymicrobial Interactions and Biofilm Formation in the Gram-Positive Actinobacterium Actinomyces oris.

PubMed

Sanchez, Belkys C; Chang, Chungyu; Wu, Chenggang; Tran, Bryan; Ton-That, Hung

2017-06-20

The Gram-positive actinobacteria Actinomyces spp. are key colonizers in the development of oral biofilms due to the inherent ability of Actinomyces to adhere to receptor polysaccharides on the surface of oral streptococci and host cells. This receptor-dependent bacterial interaction, or coaggregation, requires a unique sortase-catalyzed pilus consisting of the pilus shaft FimA and the coaggregation factor CafA forming the pilus tip. While the essential role of the sortase machine SrtC2 in pilus assembly, biofilm formation, and coaggregation has been established, little is known about trans -acting factors contributing to these processes. We report here a large-scale Tn 5 transposon screen for mutants defective in Actinomyces oris coaggregation with Streptococcus oralis We obtained 33 independent clones, 13 of which completely failed to aggregate with S. oralis , and the remainder of which exhibited a range of phenotypes from severely to weakly defective coaggregation. The former had Tn 5 insertions in fimA , cafA , or srtC2 , as expected; the latter were mapped to genes coding for uncharacterized proteins and various nuo genes encoding the NADH dehydrogenase subunits. Electron microscopy and biochemical analyses of mutants with nonpolar deletions of nuo genes and ubiE , a menaquinone C-methyltransferase-encoding gene downstream of the nuo locus, confirmed the pilus and coaggregation defects. Both nuoA and ubiE mutants were defective in oxidation of MdbA, the major oxidoreductase required for oxidative folding of pilus proteins. Furthermore, supplementation of the ubiE mutant with exogenous menaquinone-4 rescued the cell growth and pilus defects. Altogether, we propose that the A. oris electron transport chain is biochemically linked to pilus assembly via oxidative protein folding. IMPORTANCE The Gram-positive actinobacterium A. oris expresses adhesive pili, or fimbriae, that are essential to biofilm formation and Actinomyces interactions with other bacteria

42 CFR 93.403 - ORI review of research misconduct proceedings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false ORI review of research misconduct proceedings. 93... POLICIES ON RESEARCH MISCONDUCT Responsibilities of the U.S. Department of Health and Human Services Research Misconduct Issues § 93.403 ORI review of research misconduct proceedings. ORI may conduct reviews...

42 CFR 93.403 - ORI review of research misconduct proceedings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false ORI review of research misconduct proceedings. 93... POLICIES ON RESEARCH MISCONDUCT Responsibilities of the U.S. Department of Health and Human Services Research Misconduct Issues § 93.403 ORI review of research misconduct proceedings. ORI may conduct reviews...

42 CFR 93.403 - ORI review of research misconduct proceedings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false ORI review of research misconduct proceedings. 93... POLICIES ON RESEARCH MISCONDUCT Responsibilities of the U.S. Department of Health and Human Services Research Misconduct Issues § 93.403 ORI review of research misconduct proceedings. ORI may conduct reviews...

42 CFR 93.403 - ORI review of research misconduct proceedings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false ORI review of research misconduct proceedings. 93... POLICIES ON RESEARCH MISCONDUCT Responsibilities of the U.S. Department of Health and Human Services Research Misconduct Issues § 93.403 ORI review of research misconduct proceedings. ORI may conduct reviews...

42 CFR 93.403 - ORI review of research misconduct proceedings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false ORI review of research misconduct proceedings. 93... POLICIES ON RESEARCH MISCONDUCT Responsibilities of the U.S. Department of Health and Human Services Research Misconduct Issues § 93.403 ORI review of research misconduct proceedings. ORI may conduct reviews...

Smoking in pregnancy a key factor for sudden infant death among Māori.

PubMed

MacFarlane, M; Mitchell, E A; Thompson, J M D; Lawton, B; Zuccollo, J; Elder, D; Taylor, B; McDonald, G; Stewart, A W; Percival, T; Baker, N; Schlaud, M; Fleming, P

2018-06-05

To examine the Sudden Unexpected Death in Infancy (SUDI) disparity between Māori and non-Māori in New Zealand. A nationwide prospective case-control study ran from March 2012-February 2015. Exposure to established SUDI risk factors was analysed to investigate the disparity experienced by Māori. Infant ethnicity was based on mother's ethnicity. Māori ethnicity was prioritised. Non-Māori includes Pacific, Asian, NZ European and Other. There were 137 cases and 649 controls. The Māori SUDI rate was 1.41/1,000 live births compared to 0.53/1,000 for non-Māori. Parents/caregivers of 133 cases (97%) and 258 controls (40%) were interviewed. Smoking in pregnancy was associated with an equally-increased SUDI risk for Māori (adjusted OR=8.11, 95%CI=2.64, 24.93) and non-Māori (aOR=5.09, 95% CI=1.79, 14.47), as was bed-sharing (aOR=3.66, 95% CI=1.49, 9.00 versus aOR=11.20, 95% CI=3.46, 36.29). Bed-sharing prevalence was similar, however more Māori controls smoked during pregnancy (46.7%) than non-Māori (22.8%). The main contributor relating to increased SUDI risk for Māori/non-Māori infants is the combination of smoking in pregnancy and bed-sharing. The association between known SUDI risk factors, including bed-sharing and/or smoking in pregnancy and SUDI risk, is the same regardless of ethnicity. Māori infants are exposed more frequently to both behaviours because of the higher Māori smoking rate. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Pinnacle of life--Māori living to advanced age.

PubMed

Dyall, Lorna; Kerse, Ngaire; Hayman, Karen; Keeling, Sally

2011-03-25

The purpose of this feasibility study was to investigate whether Māori of advanced age would be interested in and able to take part in a quantitative study involving a comprehensive questionnaire, physical health assessment and blood analyses (a range of biological markers). The study also aimed to involve older Māori in all stages: development of research questions, review of assessment techniques and interpretation of results. Māori aged 75-79 years living in the Bay of Plenty and Lakes DHB areas were invited to participate in a feasibility study covering a wide range of quantitative health related questions. After informed consent interviews and physical assessments were conducted in participants' homes or at a local clinic by Māori health providers contracted as a research partner. For those who gave informed consent specifically for blood analyses, bloods were taken and analysed for defined biological markers of inflammation and ageing. All physical assessments and blood analyses were forwarded to each participant's own general practitioner and relevant guidance was given by the research team. Collective results from 33 Māori participants are presented and cover: Te Reo Māori me ona tikanga (Māori language and cultural knowledge), tribal and whanau (extended family) links, cultural values and religion, whanau engagement and recreational activities, health status, healthy eating and discrimination. The Te Whare Tapa Wha model of health and the Poutama model of human development are utilised to provide an overall framework and context to present the results in respect of our participants and to celebrate their 'advanced' old age. The feasibility study has been successful in engagement with older Māori. It has paved the way to implement a subsequent longitudinal study which aims to enrol 600 Māori aged 80 to 90 years and 600 non-Māori aged 85 years in the Bay of Plenty and Lakes District Health Board areas (Tauranga, Rotorua, Whakatane, Opotiki and Te

The Brightening of the Red Supergiant alpha Ori

NASA Astrophysics Data System (ADS)

Wasatonic, R. P.; Guinan, E. F.

2016-09-01

We have been carrying out V-band and Wing TiO-band and Near-IR photoelectric photometry of the semi-regular variable red supergiant alpha Ori (Betelgeuse) over last 20 yrs. Photometry obtained during early to mid September 2016 indicates that the star is at (or near) maximum light at = +0.29 mag. Measures of TiO-band and near-IR colors indicate that alpha Ori has undergone a temperature increase of about +120 K and has an estimated spectral type of M0.5 Iab. Because alpha Ori is one of the nearest Type II SN progenitors, it an important star to monitor.

Organization of the central control of muscles of facial expression in man

PubMed Central

Root, A A; Stephens, J A

2003-01-01

Surface EMGs were recorded simultaneously from ipsilateral pairs of facial muscles while subjects made three different common facial expressions: the smile, a sad expression and an expression of horror, and three contrived facial expressions. Central peaks were found in the cross-correlograms of EMG activity recorded from the orbicularis oculi and zygomaticus major during smiling, the corrugator and depressor anguli oris during the sad look and the frontalis and mentalis during the horror look. The size of the central peak was significantly greater between the orbicularis oculi and zygomaticus major during smiling. It is concluded that co-contraction of facial muscles during some facial expressions are accompanied by the presence of common synaptic drive to the motoneurones supplying the muscles involved. Central peaks were found in the cross-correlograms of EMG activity recorded from the frontalis and depressor anguli oris during a contrived expression. However, no central peaks were found in the cross-correlograms of EMG activity recorded from the frontalis and orbicularis oculi or from the frontalis and zygomaticus major during the other two contrived expressions. It is concluded that a common synaptic drive is not present between all possible facial muscle pairs and suggests a functional role for the synergy. The origin of the common drive is discussed. It is concluded that activity in branches of common stem last-order presynaptic input fibres to motoneurones innervating the different facial muscles and presynaptic synchronization of input activity to the different motoneurone pools is involved. The former probably contributes more to the drive to the orbicularis oculi and zygomaticus major during smiling, while the latter is probably more prevalent in the corrugator and depressor anguli oris during the sad look, the frontalis and mentalis during the horror look and the frontalis and depressor anguli oris during one of the contrived expressions. The strength

Progressive Cl- channel defects reveal disrupted skeletal muscle maturation in R6/2 Huntington's mice.

PubMed

Miranda, Daniel R; Wong, Monica; Romer, Shannon H; McKee, Cynthia; Garza-Vasquez, Gabriela; Medina, Alyssa C; Bahn, Volker; Steele, Andrew D; Talmadge, Robert J; Voss, Andrew A

2017-01-01

Huntington's disease (HD) patients suffer from progressive and debilitating motor dysfunction. Previously, we discovered reduced skeletal muscle chloride channel (ClC-1) currents, inwardly rectifying potassium (Kir) channel currents, and membrane capacitance in R6/2 transgenic HD mice. The ClC-1 loss-of-function correlated with increased aberrant mRNA processing and decreased levels of full-length ClC-1 mRNA (Clcn1 gene). Physiologically, the resulting muscle hyperexcitability may help explain involuntary contractions of HD. In this study, the onset and progression of these defects are investigated in R6/2 mice, ranging from 3 wk old (presymptomatic) to 9-13 wk old (late-stage disease), and compared with age-matched wild-type (WT) siblings. The R6/2 ClC-1 current density and level of aberrantly spliced Clcn1 mRNA remain constant with age. In contrast, the ClC-1 current density increases, and the level of aberrantly spliced Clcn1 mRNA decreases with age in WT mice. The R6/2 ClC-1 properties diverge from WT before the onset of motor symptoms, which occurs at 5 wk of age. The relative decrease in R6/2 muscle capacitance also begins in 5-wk-old mice and is independent of fiber atrophy. Kir current density is consistently lower in R6/2 compared with WT muscle. The invariable R6/2 ClC-1 properties suggest a disruption in muscle maturation, which we confirm by measuring elevated levels of neonatal myosin heavy chain (MyHC) in late-stage R6/2 skeletal muscle. Similar changes in ClC-1 and MyHC isoforms in the more slowly developing Q175 HD mice suggest an altered maturational state is relevant to adult-onset HD. Finally, we find nuclear aggregates of muscleblind-like protein 1 without predominant CAG repeat colocalization in R6/2 muscle. This is unlike myotonic dystrophy, another trinucleotide repeat disorder with similar ClC-1 defects, and suggests a novel mechanism of aberrant mRNA splicing in HD. These early and progressive skeletal muscle defects reveal much needed

Suppression of initiation defects of chromosome replication in Bacillus subtilis dnaA and oriC-deleted mutants by integration of a plasmid replicon into the chromosomes.

PubMed

Hassan, A K; Moriya, S; Ogura, M; Tanaka, T; Kawamura, F; Ogasawara, N

1997-04-01

We constructed Bacillus subtilis strains in which chromosome replication initiates from the minimal replicon of a plasmid isolated from Bacillus natto, independently of oriC. Integration of the replicon in either orientation at the proA locus (115 degrees on the genetic map) suppressed the temperature-sensitive phenotype caused by a mutation in dnaA, a gene required for initiation of replication from oriC. In addition, in a strain with the plasmid replicon integrated into the chromosome, we were able to delete sequences required for oriC function. These strains were viable but had a slower growth rate than the oriC+ strains. Marker frequency analysis revealed that both pyrD and metD, genes close to proA, showed the highest values among the markers (genes) measured, and those of other markers decreased symmetrically with distance from the site of the integration (proA). These results indicated that the integrated plasmid replicon operated as a new and sole origin of chromosome replication in these strains and that the mode of replication was bidirectional. Interestingly, these mutants produced anucleate cells at a high frequency (about 40% in exponential culture), and the distribution of chromosomes in the cells was irregular. A change in the site and mechanism (from oriC to a plasmid system) of initiation appears to have resulted in a drastic alteration in coordination between chromosome replication and chromosome partition or cell division.

Unravelling the whāriki of Crown Māori health infrastructure.

PubMed

Came, Heather; Tudor, Keith

2017-07-07

New Zealand's central government, and more specifically the Ministry of Health, consistently acknowledges their special relationship with Māori and the strategic importance of Māori health, and certainly, strengthening Māori health is critical to addressing systemic health inequities. This paper, framed in terms of the Crown principles attributed to the Treaty of Waitangi, ie, participation, protection and partnership, examines three structural decisions that threaten to unravel the whāriki (foundational mat) of Crown Māori health policy infrastructure. These include the disestablishment of the Ministry of Health's policy team, Te Kete Hauora, revoking mandatory district health boards' (DHB) Māori health plans and reporting, and downscaling the requirements of DHBs to consult. These actions appear to breach the Articles of te Tiriti o Waitangi and may be cited as such in the forthcoming WAI 2575 kaupapa health hearing before the Waitangi Tribunal. The authors call for the Ministry of Health to embrace its Treaty obligations, and to protect and reinstate the whāriki of Māori health infrastructure.

Replication origins oriGNAI3 and oriB of the mammalian AMPD2 locus nested in a region of straight DNA flanked by intrinsically bent DNA sites.

PubMed

Balani, Valério Américo; de Lima Neto, Quirino Alves; Takeda, Karen Izumi; Gimenes, Fabrícia; Fiorini, Adriana; Debatisse, Michelle; Fernandez, Maria Aparecida

2010-11-01

The aim of this work was to determine whether intrinsically bent DNA sites are present at, or close to, the mammalian replication origins oriGNAI3 and oriB in the Chinese hamster AMPD2 locus. Using an electrophoretic mobility shift assay and in silico analysis, we located four intrinsically bent DNA sites (b1 to b4) in a fragment that contains the oriGNAI3 and one site (b5) proximal to oriB. The helical parameters show that each bent DNA site is curved in a left-handed superhelical writhe. A 2D projection of 3D fragment trajectories revealed that oriGNAI3 is located in a relatively straight segment flanked by bent sites b1 and b2, which map in previously identified Scaffold/Matrix Attachment Region. Sites b3 and b4 are located approximately 2 kb downstream and force the fragment into a strong closed loop structure. The b5 site is also located in an S/MAR that is found just downstream of oriB.

Achieving health equity in Aotearoa: strengthening responsiveness to Māori in health research.

PubMed

Reid, Papaarangi; Paine, Sarah-Jane; Curtis, Elana; Jones, Rhys; Anderson, Anneka; Willing, Esther; Harwood, Matire

2017-11-10

Excellent health research is essential for good health outcomes, services and systems. Health research should also build towards equity and in doing so ensure that no one is left behind. As recipients of government funding, researchers are increasingly required to demonstrate an understanding of their delegated responsibilities to undertake research that has the potential to address Māori health needs and priorities. These requirements form the basis of responsiveness to Māori in health research, and several research institutions have implemented systems to support their organisational approach to this endeavour. However, many health researchers have a narrow view of responsiveness to Māori and how it might be relevant to their work. In this viewpoint paper we provide an overview of existing frameworks that can be used to develop thinking and positioning in relation to the Treaty of Waitangi and responsiveness to Māori. We also describe an equity-based approach to responsiveness to Māori and highlight four key areas that require careful consideration, namely: (1) relevance to Māori; (2) Māori as participants; (3) promoting the Māori voice, and; (4) human tissue. Finally, we argue for greater engagement with responsiveness to Māori activities as part of our commitment to achieving equitable health outcomes.

Use of the rectus abdominis muscle flap to fill a retroperitoneal defect following blast injury.

PubMed

Talarczyk, Matthew R; Ricci, Michael A

2009-02-01

Wartime injuries from explosive devices have created the need for atypical responses to devastating and unusual injuries. We report a case of an explosive abdominal injury that produced a huge defect in the posterior abdominal wall which was ultimately repaired with a rectus abdominus flap, an usual use of this versatile muscle flap. The rectus abdominus muscle may be another tool available for the repair of wartime injuries.

Mortality trends in Australian Aboriginal peoples and New Zealand Māori.

PubMed

Phillips, Bronwen; Daniels, John; Woodward, Alistair; Blakely, Tony; Taylor, Richard; Morrell, Stephen

2017-01-01

The health status of Indigenous populations of Australia and New Zealand (NZ) Māori manifests as life expectancies substantially lower than the total population. Accurate assessment of time trends in mortality and life expectancy allows evaluation of progress in reduction of health inequalities compared to the national or non-Indigenous population. Age-specific mortality and life expectancy (at birth) (LE) for Indigenous populations (Australia from 1990 and NZ from 1950); and all Australia and non-Māori NZ (from 1890), males (M) and females (F), were obtained from published sources and national statistical agency reports. Period trends were assessed for credible estimates of Indigenous LE, and the LE gap compared to the total population for Australia, and non-Māori for NZ. Period trends in premature adult mortality, as cumulative probability of dying over 15-59 years, were assessed similarly. The relative contribution of differences in age-specific mortality to the LE gap between Indigenous and the all-Australia population, and the non-Māori NZ, was estimated for each country by sex for the most recent period: 2010-2012 for Australia, 2012-2014 for NZ. LE increased for all populations, although LE gaps between Indigenous and all Australia showed little change over time. LE gaps between NZ Māori and non-Māori increased significantly from the early 1980s to the mid-1990s, and since then have fallen again. Recent LE gaps in Australia (M 12.5; F 12.0 years in 2010-2012) were larger than in NZ (M 7.3; F 6.8 years in 2012-2014). Premature adult mortality (15-59 years) improved for all populations, but mortality ratios show little change since 2000, with Indigenous at 3½-4 times that of all Australians, and Māori 2-3 times that of non-Māori. Using decomposition analysis, the age interval contributing most strongly to differences in LE between Indigenous and all Australia was 35-59 years, but between Māori and non-Māori it was 60-74 years. In Australia and

Progressive Cl− channel defects reveal disrupted skeletal muscle maturation in R6/2 Huntington’s mice

PubMed Central

Miranda, Daniel R.; Wong, Monica; Romer, Shannon H.; McKee, Cynthia; Garza-Vasquez, Gabriela; Medina, Alyssa C.; Bahn, Volker; Steele, Andrew D.; Talmadge, Robert J.

2017-01-01

Huntington’s disease (HD) patients suffer from progressive and debilitating motor dysfunction. Previously, we discovered reduced skeletal muscle chloride channel (ClC-1) currents, inwardly rectifying potassium (Kir) channel currents, and membrane capacitance in R6/2 transgenic HD mice. The ClC-1 loss-of-function correlated with increased aberrant mRNA processing and decreased levels of full-length ClC-1 mRNA (Clcn1 gene). Physiologically, the resulting muscle hyperexcitability may help explain involuntary contractions of HD. In this study, the onset and progression of these defects are investigated in R6/2 mice, ranging from 3 wk old (presymptomatic) to 9–13 wk old (late-stage disease), and compared with age-matched wild-type (WT) siblings. The R6/2 ClC-1 current density and level of aberrantly spliced Clcn1 mRNA remain constant with age. In contrast, the ClC-1 current density increases, and the level of aberrantly spliced Clcn1 mRNA decreases with age in WT mice. The R6/2 ClC-1 properties diverge from WT before the onset of motor symptoms, which occurs at 5 wk of age. The relative decrease in R6/2 muscle capacitance also begins in 5-wk-old mice and is independent of fiber atrophy. Kir current density is consistently lower in R6/2 compared with WT muscle. The invariable R6/2 ClC-1 properties suggest a disruption in muscle maturation, which we confirm by measuring elevated levels of neonatal myosin heavy chain (MyHC) in late-stage R6/2 skeletal muscle. Similar changes in ClC-1 and MyHC isoforms in the more slowly developing Q175 HD mice suggest an altered maturational state is relevant to adult-onset HD. Finally, we find nuclear aggregates of muscleblind-like protein 1 without predominant CAG repeat colocalization in R6/2 muscle. This is unlike myotonic dystrophy, another trinucleotide repeat disorder with similar ClC-1 defects, and suggests a novel mechanism of aberrant mRNA splicing in HD. These early and progressive skeletal muscle defects reveal much needed

Polar-phase indices of perioral muscle reciprocity during syllable production in Parkinson's disease.

PubMed

Chu, Shin Ying; Barlow, Steven M; Lee, Jaehoon; Wang, Jingyan

2017-12-01

This research characterised perioral muscle reciprocity and amplitude ratio in lower lip during bilabial syllable production [pa] at three rates to understand the neuromotor dynamics and scaling of motor speech patterns in individuals with Parkinson's disease (PD). Electromyographic (EMG) signals of the orbicularis oris superior [OOS], orbicularis oris inferior [OOI] and depressor labii inferioris [DLI] were recorded during syllable production and expressed as polar-phase notations. PD participants exhibited the general features of reciprocity between OOS, OOI and DLI muscles as reflected in the EMG during syllable production. The control group showed significantly higher integrated EMG amplitude ratio in the DLI:OOS muscle pairs than PD participants. No speech rate effects were found in EMG muscle reciprocity and amplitude magnitude across all muscle pairs. Similar patterns of muscle reciprocity in PD and controls suggest that corticomotoneuronal output to the facial nucleus and respective perioral muscles is relatively well-preserved in our cohort of mild idiopathic PD participants. Reduction of EMG amplitude ratio among PD participants is consistent with the putative reduction in the thalamocortical activation characteristic of this disease which limits motor cortex drive from generating appropriate commands which contributes to bradykinesia and hypokinesia of the orofacial mechanism.

Strengthening Māori participation in the New Zealand health and disability workforce.

PubMed

Ratima, Mihi M; Brown, Rachel M; Garrett, Nick K G; Wikaire, Erena I; Ngawati, Renei M; Aspin, Clive S; Potaka, Utiku K

2007-05-21

Substantial progress has been made in Māori health and disability workforce development in the past 15 years. Key factors in successful programs to increase Māori health workforce recruitment and retention include Māori leadership, mentorship and peer support; and comprehensive support within study programs and in the transitions between school, university and work. The interventions to date provide a strong basis for ongoing action to address inequities in Māori health workforce participation, and are likely to be relevant to health workforce development approaches for other indigenous peoples.

The Chandra/MOST Campaign on Delta Ori A

NASA Astrophysics Data System (ADS)

Corcoran, Michael

2014-11-01

X-ray emission from massive stars is produced by shocked gas distributed throughout their unstable stellar winds. These shocks play a significant role in determining accurate stellar mass loss rates. Our current understanding of these shocks is derived from indirect indicators like line profile shapes and the f/i ratio of the He-like triplets. Here we discuss a campaign of phase-resolved Chandra grating observations and simultaneous high-precision photometry using the MOST satellite of the massive binary Delta Ori A, in an attempt to directly constrain the radial extent of the hot gas in the wind of the primary star (Delta Ori Aa) via occultation by the X-ray faint secondary (Delta Ori Ab). We present an overview of this campaign and a summary of our results.

Factors associated with nutrition risk in older Māori: a cross sectional study.

PubMed

Wham, Carol; Maxted, Eruera; Teh, Ruth; Kerse, Ngaire

2015-08-21

To investigate factors associated with nutrition risk among older Māori. Māori aged 75-79 years living in the Northland and Bay of Plenty regions of New Zealand were assessed for nutrition risk using the validated screening tool 'Seniors in the Community: Risk Evaluation for Eating and Nutrition' (SCREENII). Demographic, physical and sociocultural data were collected. Of the 67 participants, two thirds (63%) were identified to be at high-risk for malnutrition. More than half (56%) used te reo Māori (Māori language) for everyday conversation and those who rated language and culture as moderately important to wellbeing were at lower nutrition risk. Controlling for age, gender and living arrangements, participants who rated traditional foods as important, were able to access them, had a higher waist-to-hip ratio and an absence of depressive symptoms, were at lower nutrition risk. Cultural factors associated with nutrition risk are related to an indigenous view of health. Participants with a higher waist-to-hip ratio were at lower nutrition risk and this may be a protective factor for older Māori. Interventions to improve the nutrition status of older Māori need to be based on a holistic Māori worldview and acknowledge the importance of traditional Māori foods.

Muscle tension line concept in nasolabial muscle complex--based on 3-dimensional reconstruction of nasolabial muscle fibers.

PubMed

Yin, Ningbei; Wu, Jiajun; Chen, Bo; Song, Tao; Ma, Hengyuan; Zhao, Zhenmin; Wang, Yongqian; Li, Haidong; Wu, Di

2015-03-01

Plastic surgeons have attempted various ways to rebuild the aesthetic subunits of the upper lip in patients with cleft lip with less than perfect results in most cases. We propose that repairing the 3 muscle tension line groups in the nasolabial complex will have improved aesthetic results. Micro-computed tomographic scans were performed on the nasolabial tissues of 5 normal aborted fetuses and used to construct a 3-dimensional model to study the nasolabial muscle complex structure. The micro-computed tomographic (CT) scans showed the close relationship and interaction between the muscle fibers of nasalis, pars peripheralis, levator labii superioris, and pars marginalis. Based on the 2-dimensional images obtained from the micro-computed tomographic scans, we suggest the concept of nasolabial muscle complex and muscle tension line group theory: there is a close relationship among the alar part of the nasalis, depressor septi muscle, orbicularis oris muscle, and levator labii superioris alaeque nasi. The tension line groups are 3 tension line structures in the nasolabial muscle complex that interlock with each other at the intersections and maintain the specific shape and aesthetics of the lip and nose.

Exercise to Support Indigenous Pregnant Women to Stop Smoking: Acceptability to Māori.

PubMed

Roberts, Vaughan; Glover, Marewa; McCowan, Lesley; Walker, Natalie; Ussher, Michael; Heke, Ihirangi; Maddison, Ralph

2017-11-01

Objectives Smoking during pregnancy is harmful for the woman and the unborn child, and the harms raise risks for the child going forward. Indigenous women often have higher rates of smoking prevalence than non-indigenous. Exercise has been proposed as a strategy to help pregnant smokers to quit. Māori (New Zealand Indigenous) women have high rates of physical activity suggesting that an exercise programme to aid quitting could be an attractive initiative. This study explored attitudes towards an exercise programme to aid smoking cessation for Māori pregnant women. Methods Focus groups with Māori pregnant women, and key stakeholder interviews were conducted. Results Overall, participants were supportive of the idea of a physical activity programme for pregnant Māori smokers to aid smoking cessation. The principal, over-arching finding, consistent across all participants, was the critical need for a Kaupapa Māori approach (designed and run by Māori, for Māori people) for successful programme delivery, whereby Māori cultural values are respected and infused throughout all aspects of the programme. A number of practical and environmental barriers to attendance were raised including: cost, the timing of the programme, accessibility, transport, and childcare considerations. Conclusions A feasibility study is needed to design an intervention following the suggestions presented in this paper with effort given to minimising the negative impact of barriers to attendance.

Anatomy of the depressor septi nasi muscle: the basis for correction of deformities of the nose/lip junction.

PubMed

Barbosa, Marcus Vinícius Jardini; Nahas, Fábio Xerfan; Ferreira, Lydia Masako

2013-04-01

The purpose of this study was to analyse the macroscopic aspect of the depressor septi nasi muscle in cadavers according to its relations with the nasolabial region, and to describe a surgical technique developed out of the knowledge gained from its study to take care of nasal tip drooping and gummy smile. Twenty fresh adult cadavers were studied. All of them were men. A transverse incision was done at the gingivo-labial sulcus, through the frenulum, to expose the orbicularis oris and the depressor nasi muscles. These muscles were isolated and their anatomical aspect, localisation, origin, and insertion were registered. Sixteen of the cadavers presented the muscle. From these, 14 were bilateral and two were unilateral. Four cadavers did not present the muscle. Muscular fibres were vertically disposed and presented oblique direction towards the midline, in a quadrangular shape. From the 16 cadavers of the subgroup in whom the muscle was present, 14 originated in the orbicularis oris and its insertion was in the maxilla. Two of the cadavers presented the origin and insertion at the maxilla. According to these findings, a surgical approach of the muscles was proposed to treat the gummy smile deformity during rhinoplasty and two clinical cases are presented. The depressor nasi muscles presented an anatomical variation. In most cases it is intimately related with the orbicularis oris and the maxilla, being a relatively thick structure. We suggest its treatment simultaneously during rhinoplasty for a better result of the nasal tip and it benefits the "tense nose" aspect and the smiling deformity.

The reverse sural artery fasciomusculocutaneous flap for small lower-limb defects: the use of the gastrocnemius muscle cuff as a plug for small bony defects following debridement of infected/necrotic bone.

PubMed

Al-Qattan, M M

2007-09-01

The reverse sural artery fasciomusculocutaneous flap is a modification of the original fasciocutaneous flap in which a midline gastrocnemius muscle cuff around the buried sural pedicle is included in the flap. This modification was done to improve the blood supply of the distal part of the flap, which is harvested from the upper leg. The aim of this paper is to demonstrate that there is another important advantage of the modified flap: the use of the muscle cuff as a "plug" for small lower limb defects following debridement of infected/necrotic bone. A total of 10 male adult patients with small complex lower-limb defects with underlying bone pathology were treated with the modified flap using the muscle component to fill up the small bony defects. The bony pathology included necrotic exposed bone without evidence of osteomyelitis or wound infection (n = 1), an underlying neglected tibial fracture with wound infection (n = 4), and a sinus at the heel with underlying calcaneal osteomyelitis (n = 5). Primary wound healing of the flap into the defect was noted in all patients. No recurrence of calcaneal osteomyelitis was seen and all tibial fractures united following appropriate orthopedic fixation. It was concluded that the reverse sural artery fasciomusculocutaneous flap is well suited for small complex lower-limb defects with underlying bone pathology.

[Simultaneous repairing defects of orbital floor and palate with the modified temporalis muscle flap after the maxillectomy].

PubMed

Zhong, Q; Huang, Z G; Fang, J G; Chen, X J; Chen, X H; Hou, L Z; Li, P D; Ma, H Z; He, S Z

2016-09-07

Objective: To evaluate the outcome of one-stage reconstruction of maxillary and orbital defects with modified temporalis muscle flap (TMF) following the removal of malignant neoplasms. Methods: In this retrospective study, 15 patients underwent the reconstruction of defects of orbital floor and palate after maxillectomy for malignant tumor were included from June 2008 to June 2014. The modified temporalis muscle flap was used to repair the defects after surgery, and functional outcomes were analyzed. Results: All the patients were followed up for 12-81 months. Three cases of them received preoperative radiotherapy and 12 cases underwent postoperative radiotherapy. All flaps were survived. Epithelization of the tissues in oral and nasal cavity was completed in 4-6 weeks. Good functional reconstruction on swallowing and speaking functional results were achieved with maxillary and orbital reconstruction and no secondary deformity of external nose was observed. The eye positions in all cases were normal. Diplopia, diminution and loss of vision were not found. Conclusion: The modified TMF can be used for simultaneous reconstruction for the defects of orbital floor and palate after maxillectomy in patients whom free tissue flap can not be applied to, showing better cosmetic and functional results.

Experience with 32 Pelvic Fracture Urethral Defects Associated with Urethrorectal Fistulas: Transperineal Urethroplasty with Gracilis Muscle Interposition.

PubMed

Guo, Hailin; Sa, Yinglong; Fu, Qiang; Jin, Chongrui; Wang, Lin

2017-07-01

Pelvic fracture urethral defects associated with urethrorectal fistulas are rare and difficult to repair. The aim of this study was to evaluate the efficacy of transperineal urethroplasty with gracilis muscle interposition for the repair of pelvic fracture urethral defects associated with urethrorectal fistulas. We identified 32 patients who underwent transperineal urethroplasty with gracilis muscle interposition to repair pelvic fracture urethral defects associated with urethrorectal fistulas. Patient demographics as well as preoperative, operative and postoperative data were obtained. Mean followup was 33 months (range 6 to 64). The overall success rate was 91% (29 of 32 cases). One-stage repair was successful in 17 of 18 patients (94%) using perineal anastomosis with separation of the corporeal body and in 12 of 14 (86%) using perineal anastomosis with inferior pubectomy and separation of the corporeal body. All 22 patients (100%) without a previous history of repair were successfully treated. However, only 7 of 10 patients (70%) with a previous history of failed urethroplasty and urethrorectal fistula repair were cured. Recurrent urethral strictures developed in 2 cases. One patient was treated successfully with optical internal urethrotomy and the other was treated successfully with tubed perineoscrotal flap urethroplasty. Recurrent urethrorectal fistulas associated with urethral strictures developed in an additional patient. Transperineal urethroplasty with gracilis muscle interposition is a safe and effective surgical procedure for most pelvic fracture urethral defects associated with urethrorectal fistulas. Several other factors may affect its postoperative efficiency. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Development concepts of a Smart Cyber Operating Theater (SCOT) using ORiN technology.

PubMed

Okamoto, Jun; Masamune, Ken; Iseki, Hiroshi; Muragaki, Yoshihiro

2018-02-23

Currently, networking has not progressed in the treatment room. Almost every medical device in the treatment room operates as a stand-alone device. In this project, we aim to develop a networked operating room called "Smart Cyber Operating Theater (SCOT)". Medical devices are connected using Open Resource interface for the Network (ORiN) technology. In this paper, we describe the concept of the SCOT project. SCOT is integrated using the communication interface ORiN, which was originally developed for industry. One feature of ORiN is that the system can be constructed flexibly. ORiN creates abstracts of the same type of devices and increases the robustness of the system for device exchange. By using ORiN technology, we are developing new applications, such as decision-making navigation or a precision guided treatment system.

Predictors of academic success for Māori, Pacific and non-Māori non-Pacific students in health professional education: a quantitative analysis.

PubMed

Wikaire, Erena; Curtis, Elana; Cormack, Donna; Jiang, Yannan; McMillan, Louise; Loto, Rob; Reid, Papaarangi

2017-05-01

Tertiary institutions internationally aim to increase student diversity, however are struggling to achieve equitable academic outcomes for indigenous and ethnic minority students and detailed exploration of factors that impact on success is required. This study explored the predictive effect of admission variables on academic outcomes for health professional students by ethnic grouping. Kaupapa Māori and Pacific research methodologies were used to conduct a quantitative analysis using data for 2686 health professional students [150 Māori, 257 Pacific, 2279, non-Māori non-Pacific (nMnP)]. The predictive effect of admission variables: school decile; attending school in Auckland; type of admission; bridging programme; and first-year bachelor results on academic outcomes: year 2-4 grade point average (GPA); graduating; graduating in the minimum time; and optimal completion for the three ethnic groupings and the full cohort was explored using multiple regression analyses. After adjusting for admission variables, for every point increase in first year bachelor GPA: year 2-4 GPA increased by an average of 0.46 points for Māori (p = 0.0002, 95% CI 0.22, 0.69), 0.70 points for Pacific (p < 0.0001, CI 0.52, 0.87), and 0.55 points for nMnP (p < 0.0001, CI 0.51, 0.58) students. For the total cohort, ethnic grouping was consistently the most significant predictor of academic outcomes. This study demonstrated clear differences in academic outcomes between both Māori and Pacific students when compared to nMnP students. Some (but not all) of the disparities between ethnic groupings could be explained by controlling for admission variables.

Pectoralis major muscle defect and Poland complex.

PubMed

Castilla, E E; Paz, J E; Orioli, I M

1979-01-01

Pectoralis major muscle defect (PMD) was diagnosed in 27 infants from a series of 599,109 live births in South America (1/22,189). In all 27 cases the PMD was unilateral, mainly affecting the right side (20/27), and there were more male (19/27) than female cases. No familial cases and no parental consanguinity were recorded. A positive correlation was observed between PMD and sex hormone intake and vaginal bleeding in the first trimester of pregnancy. In 12 (1/49,925) of the 27 PMD cases hypoplasia and/or syndactyly of the ipsilateral hand was also diagnosed. The index-middle interdigital space was affected in all 11 cases with symbrachydactyly. Additional congenital anomalies were observed in 4/27 cases, and they were: hemangiomas, hypospadias, and clubfeet. Poland complex (12 cases), isolated PMD (15 cases), and isolated symbrachydactyly (18 cases), showed a similar pattern for symmetry, sidedness, syndactyly type, and sex ratio.

Differences in patients' perceptions of Schizophrenia between Māori and New Zealand Europeans.

PubMed

Sanders, Deanna; Kydd, Robert; Morunga, Eva; Broadbent, Elizabeth

2011-06-01

Māori (the Indigenous people of New Zealand) are disproportionately affected by mental illness and experience significantly poorer mental health compared to New Zealand Europeans. It is important to understand cultural differences in patients' ideas about mental illness in treatment settings. The aim of the present study was to investigate differences in illness perceptions between Māori and New Zealand Europeans diagnosed with schizophrenia. A total of 111 users of mental health services (68 Māori, 43 New Zealand European) in the greater Auckland and Northland areas who had been diagnosed with schizophrenia or other psychotic disorder were interviewed using the Brief Illness Perception Questionnaire and the Drug Attitude Inventory. District Health Board staff completed the Global Assessment of Functioning for each patient. Māori with schizophrenia believed that their illness would continue significantly less time than New Zealand European patients did. Chance or spiritual factors were listed as causes of mental illness by only five Māori patients and no New Zealand European patients. Other illness perceptions, as well as attitudes towards medication, were comparable between groups. Across groups, the top perceived causes were drugs/alcohol, family relationships/abuse, and biological causes. Illness perceptions provide a framework to assess patients' beliefs about their mental illness. Differences between Māori and New Zealand European patients' beliefs about their mental illness may be related to traditional Māori beliefs about mental illness. Knowledge of differences in illness perceptions provides an opportunity to design effective clinical interventions for both Māori and New Zealand Europeans.

OriDB, the DNA replication origin database updated and extended.

PubMed

Siow, Cheuk C; Nieduszynska, Sian R; Müller, Carolin A; Nieduszynski, Conrad A

2012-01-01

OriDB (http://www.oridb.org/) is a database containing collated genome-wide mapping studies of confirmed and predicted replication origin sites. The original database collated and curated Saccharomyces cerevisiae origin mapping studies. Here, we report that the OriDB database and web site have been revamped to improve user accessibility to curated data sets, to greatly increase the number of curated origin mapping studies, and to include the collation of replication origin sites in the fission yeast Schizosaccharomyces pombe. The revised database structure underlies these improvements and will facilitate further expansion in the future. The updated OriDB for S. cerevisiae is available at http://cerevisiae.oridb.org/ and for S. pombe at http://pombe.oridb.org/.

Chromosomal insertions localized around oriC affect the cell cycle in Escherichia coli.

PubMed

Molina, F; Jiménez-Sánchez, A; Zyskind, J W; Guzmán, E C

1999-01-01

The present work reports the effects of localized insertions around the origin of Escherichia coli chromosome, oriC, on cell cycle parameters. These insertions cause an increase of the C period with an inverse correlation to the distance from oriC. In addition, Omega insertion near oriC causes an increase in the number of replication forks per chromosome, n, and Tn10 insertion causes a decrease in growth rate. We found that the same insertion positioned in another region of the chromosome, outside of oriC, has a negligible effect on the C period. Marker frequency analysis suggests a slower replication velocity along the whole chromosome. We propose that the insertions positioned at less than 2 kbp from oriC could create a structural alteration in the origin of replication that would result in a longer C period. Flow cytometry reveals that asynchrony is not associated with these alterations.

Electron Transport Chain Is Biochemically Linked to Pilus Assembly Required for Polymicrobial Interactions and Biofilm Formation in the Gram-Positive Actinobacterium Actinomyces oris

PubMed Central

Sanchez, Belkys C.; Chang, Chungyu; Wu, Chenggang; Tran, Bryan

2017-01-01

ABSTRACT The Gram-positive actinobacteria Actinomyces spp. are key colonizers in the development of oral biofilms due to the inherent ability of Actinomyces to adhere to receptor polysaccharides on the surface of oral streptococci and host cells. This receptor-dependent bacterial interaction, or coaggregation, requires a unique sortase-catalyzed pilus consisting of the pilus shaft FimA and the coaggregation factor CafA forming the pilus tip. While the essential role of the sortase machine SrtC2 in pilus assembly, biofilm formation, and coaggregation has been established, little is known about trans-acting factors contributing to these processes. We report here a large-scale Tn5 transposon screen for mutants defective in Actinomyces oris coaggregation with Streptococcus oralis. We obtained 33 independent clones, 13 of which completely failed to aggregate with S. oralis, and the remainder of which exhibited a range of phenotypes from severely to weakly defective coaggregation. The former had Tn5 insertions in fimA, cafA, or srtC2, as expected; the latter were mapped to genes coding for uncharacterized proteins and various nuo genes encoding the NADH dehydrogenase subunits. Electron microscopy and biochemical analyses of mutants with nonpolar deletions of nuo genes and ubiE, a menaquinone C-methyltransferase-encoding gene downstream of the nuo locus, confirmed the pilus and coaggregation defects. Both nuoA and ubiE mutants were defective in oxidation of MdbA, the major oxidoreductase required for oxidative folding of pilus proteins. Furthermore, supplementation of the ubiE mutant with exogenous menaquinone-4 rescued the cell growth and pilus defects. Altogether, we propose that the A. oris electron transport chain is biochemically linked to pilus assembly via oxidative protein folding. PMID:28634238

The Ceramide Transporter CERT is Involved in Muscle Insulin Signaling Defects Under Lipotoxic Conditions.

PubMed

Bandet, Cécile L; Mahfouz, Rana; Véret, Julien; Sotiropoulos, Athanassia; Poirier, Maxime; Giussani, Paola; Campana, Mélanie; Philippe, Erwann; Blachnio-Zabielska, Agnieszka; Ballaire, Raphaëlle; Le Liepvre, Xavier; Bourron, Olivier; Berkeš, Dušan; Górski, Jan; Ferré, Pascal; Le Stunff, Hervé; Foufelle, Fabienne; Hajduch, Eric

2018-05-14

One main mechanism of insulin resistance (IR), a key feature of type-2 diabetes, is the accumulation of saturated fatty acids (FA) in muscles of obese and type-2 diabetic patients. Understanding the mechanism underlying lipid-induced IR is therefore a crucial challenge. Saturated FA are metabolized into lipid-derivatives called ceramides and their accumulation plays a central role in the development of muscle IR. Ceramides are produced in the endoplasmic reticulum (ER) and transported to the Golgi through a transporter called CERT, where they are converted into different sphingolipid species. We show here that CERT protein expression is reduced in all insulin resistance models studied due to a caspase-dependent cleavage. Inhibiting CERT activity in vitro potentiates the deleterious action of lipotoxicity on insulin signaling whereas overexpression of CERT in vitro or in vivo increases muscle ceramide content and improves insulin signaling. In addition, inhibition of caspase activity prevents ceramide-induced insulin signaling defects in C2C12 muscle cells. Altogether, these results demonstrate the importance of a physiological ER to Golgi ceramide traffic to preserve muscle cell insulin signaling and identifies CERT as a major actor in this process. © 2018 by the American Diabetes Association.

In vivo imaging of skeletal muscle in mice highlights muscle defects in a model of myotubular myopathy

PubMed Central

Mercier, Luc; Böhm, Johann; Fekonja, Nina; Allio, Guillaume; Lutz, Yves; Koch, Marc; Goetz, Jacky G.; Laporte, Jocelyn

2016-01-01

ABSTRACT Skeletal muscle structure and function are altered in different myopathies. However, the understanding of the molecular and cellular mechanisms mainly rely on in vitro and ex vivo investigations in mammalian models. In order to monitor in vivo the intracellular structure of the neuromuscular system in its environment under normal and pathological conditions, we set-up and validated non-invasive imaging of ear and leg muscles in mice. This original approach allows simultaneous imaging of different cellular and intracellular structures such as neuromuscular junctions and sarcomeres, reconstruction of the 3D architecture of the neuromuscular system, and video recording of dynamic events such as spontaneous muscle fiber contraction. Second harmonic generation was combined with vital dyes and fluorescent-coupled molecules. Skin pigmentation, although limiting, did not prevent intravital imaging. Using this versatile toolbox on the Mtm1 knockout mouse, a model for myotubular myopathy which is a severe congenital myopathy in human, we identified several hallmarks of the disease such as defects in fiber size and neuromuscular junction shape. Intravital imaging of the neuromuscular system paves the way for the follow-up of disease progression or/and disease amelioration upon therapeutic tests. It has also the potential to reduce the number of animals needed to reach scientific conclusions. PMID:28243519

Rehabilitation and indigenous peoples: the Māori experience.

PubMed

Harwood, Matire

2010-01-01

Indigenous peoples often have the worst health status in comparison to non-indigenous people in their own nations; urgent action to address the health inequities for indigenous people is required. The role of rehabilitation in addressing health and disability inequities is particularly important due to the health need of indigenous peoples; the unequal distribution of health determinants; and disparities in access to, quality of care through and outcomes following rehabilitation. This article will present a perspective for Māori, the indigenous peoples of New Zealand, on a framework for improving rehabilitation services for Māori and ultimately their health and wellbeing.

Wāhine hauora: linking local hospital and national health information datasets to explore maternal risk factors and obstetric outcomes of New Zealand Māori and non-Māori women in relation to infant respiratory admissions and timely immunisations.

PubMed

Filoche, Sara; Garrett, Susan; Stanley, James; Rose, Sally; Robson, Bridget; Elley, C Raina; Lawton, Bev

2013-07-10

Significant health inequities exist around maternal and infant health for Māori, the indigenous people of New Zealand. The infants of Māori are more likely to die in their first year of life and also have higher rates of hospital admission for respiratory illnesses, with the greatest burden of morbidity being due to bronchiolitis in those under one year of age. Timely immunisations can prevent some respiratory related hospitalisations, although for Māori, the proportion of infants with age appropriate immunisations are lower than for non-Māori. This paper describes the protocol for a retrospective cohort study that linked local hospital and national health information datasets to explore maternal risk factors and obstetric outcomes in relation to respiratory admissions and timely immunisations for infants of Māori and non-Māori women. The study population included pregnant women who gave birth in hospital in one region of New Zealand between 1995 and 2009. Routinely collected local hospital data were linked via a unique identifier (National Health Index number) to national health information databases to assess rates of post-natal admissions and access to health services for Māori and non-Māori mothers and infants. The two primary outcomes for the study are: 1. The rates of respiratory hospitalisations of infants (≤ 1 yr of age) calculated for infants of both Māori and non-Māori women (for mothers under 20 years of age, and overall) accounting for relationship to parity, maternal age, socioeconomic deprivation index, maternal smoking status. 2. The proportion of infants with age appropriate immunisations at six and 12 months, calculated for both infants born to Māori women and infants born to non-Māori women, accounting for relationship to parity, maternal age, socioeconomic deprivation index, smoking status, and other risk factors. Analysis of a wide range of routinely collected health information in which maternal and infant data are linked will

MyoD expression restores defective myogenic differentiation of human mesoangioblasts from inclusion-body myositis muscle.

PubMed

Morosetti, Roberta; Mirabella, Massimiliano; Gliubizzi, Carla; Broccolini, Aldobrando; De Angelis, Luciana; Tagliafico, Enrico; Sampaolesi, Maurilio; Gidaro, Teresa; Papacci, Manuela; Roncaglia, Enrica; Rutella, Sergio; Ferrari, Stefano; Tonali, Pietro Attilio; Ricci, Enzo; Cossu, Giulio

2006-11-07

Inflammatory myopathies (IM) are acquired diseases of skeletal muscle comprising dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM). Immunosuppressive therapies, usually beneficial for DM and PM, are poorly effective in IBM. We report the isolation and characterization of mesoangioblasts, vessel-associated stem cells, from diagnostic muscle biopsies of IM. The number of cells isolated, proliferation rate and lifespan, markers expression, and ability to differentiate into smooth muscle do not differ among normal and IM mesoangioblasts. At variance with normal, DM and PM mesoangioblasts, cells isolated from IBM, fail to differentiate into skeletal myotubes. These data correlate with lack in connective tissue of IBM muscle of alkaline phosphatase (ALP)-positive cells, conversely dramatically increased in PM and DM. A myogenic inhibitory basic helix-loop-helix factor B3 is highly expressed in IBM mesoangioblasts. Indeed, silencing this gene or overexpressing MyoD rescues the myogenic defect of IBM mesoangioblasts, opening novel cell-based therapeutic strategies for this crippling disorder.

MyoD expression restores defective myogenic differentiation of human mesoangioblasts from inclusion-body myositis muscle

PubMed Central

Morosetti, Roberta; Mirabella, Massimiliano; Gliubizzi, Carla; Broccolini, Aldobrando; De Angelis, Luciana; Tagliafico, Enrico; Sampaolesi, Maurilio; Gidaro, Teresa; Papacci, Manuela; Roncaglia, Enrica; Rutella, Sergio; Ferrari, Stefano; Tonali, Pietro Attilio; Ricci, Enzo; Cossu, Giulio

2006-01-01

Inflammatory myopathies (IM) are acquired diseases of skeletal muscle comprising dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM). Immunosuppressive therapies, usually beneficial for DM and PM, are poorly effective in IBM. We report the isolation and characterization of mesoangioblasts, vessel-associated stem cells, from diagnostic muscle biopsies of IM. The number of cells isolated, proliferation rate and lifespan, markers expression, and ability to differentiate into smooth muscle do not differ among normal and IM mesoangioblasts. At variance with normal, DM and PM mesoangioblasts, cells isolated from IBM, fail to differentiate into skeletal myotubes. These data correlate with lack in connective tissue of IBM muscle of alkaline phosphatase (ALP)-positive cells, conversely dramatically increased in PM and DM. A myogenic inhibitory basic helix–loop–helix factor B3 is highly expressed in IBM mesoangioblasts. Indeed, silencing this gene or overexpressing MyoD rescues the myogenic defect of IBM mesoangioblasts, opening novel cell-based therapeutic strategies for this crippling disorder. PMID:17077152

Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect

PubMed Central

Cao, Peirang; Hanai, Jun-ichi; Tanksale, Preeti; Imamura, Shintaro; Sukhatme, Vikas P.; Lecker, Stewart H.

2009-01-01

Statins are widely used to treat hypercholesterolemia but can lead to a number of side effects in muscle, including rhabdomyolysis. Our recent findings implicated the induction of atrogin-1, a gene required for the development of muscle atrophy, in statin-induced muscle damage. Since statins inhibit many biochemical reactions besides cholesterol synthesis, we sought to define the statin-inhibited pathways responsible for atrogin-1 expression and muscle damage. We report here that lovastatin-induced atrogin-1 expression and muscle damage in cultured mouse myotubes and zebrafish can be prevented in the presence of geranylgeranol but not farnesol. Further, inhibitors of the transfer of geranylgeranyl isoprene units to protein targets cause statin muscle damage and atrogin-1 induction in cultured cells and in fish. These findings support the concept that dysfunction of small GTP-binding proteins lead to statin-induced muscle damage since these molecules require modification by geranylgeranyl moieties for their cellular localization and activity. Collectively, our animal and in vitro findings shed light on the molecular mechanism of statin-induced myopathy and suggest that atrogin-1 may be regulated by novel signaling pathways.—Cao, P., Hanai, J., Tanksale, P., Imamura, S., Sukhatme, V. P., Lecker, S. H. Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect. PMID:19406843

Dependence on place: A source of autonomy in later life for older Māori.

PubMed

Butcher, Elizabeth; Breheny, Mary

2016-04-01

Attachment to place is an important component of ageing. Although the importance of place for older people's well-being is known, the ways in which different conceptions of place and expectations for what later life may hold depend upon cultural beliefs, values, and expectations is underexplored. This study examined the ways that place influences experiences of ageing for older Māori in New Zealand. Eight interviews with older Māori were analysed thematically alongside field notes from a research visit. Attachment to place provided the foundation for experiences of ageing for older Māori. Through their connection to place, the participants drew on a comforting and comfortable dependence on land and family to enable autonomy in later life. Rather than seeking to maintain independence in terms of avoiding reliance on others, older Māori conceptualised older age through autonomy and freedom to live in accordance with Māori values encapsulated by whakawhanaungatanga. A good old age depended on balancing competing demands of living in wider society with attachment to place and Māori identity in later life. Copyright © 2016 Elsevier Inc. All rights reserved.

Looking Māori Predicts Decreased Rates of Home Ownership: Institutional Racism in Housing Based on Perceived Appearance

PubMed Central

2015-01-01

This study examined differences in rates of home ownership among Māori (the indigenous peoples of New Zealand). We identified systematic factors that predicted why some Māori were more likely to own their own home (partially or fully) relative to other Māori. Data were drawn from a large national postal sample of 561 self-identified Māori collected as part of the New Zealand Attitudes and Values Study. As predicted, our analyses indicated that self-reported appearance as Māori, or the extent to which people thought they personally displayed features which visibly identified them as Māori to others, significantly predicted decreased rates of home ownership. This association held when adjusting for numerous demographic covariates, such as education, level of deprivation of the immediate area, household income, age, relationship status, region of residence, and so forth. Our analyses suggest there is, or at least has been in the recent past, institutional racism against Māori in New Zealand’s home lending industry based on merely appearing more Māori. PMID:25738961

Looking Māori predicts decreased rates of home ownership: institutional racism in housing based on perceived appearance.

PubMed

Houkamau, Carla A; Sibley, Chris G

2015-01-01

This study examined differences in rates of home ownership among Māori (the indigenous peoples of New Zealand). We identified systematic factors that predicted why some Māori were more likely to own their own home (partially or fully) relative to other Māori. Data were drawn from a large national postal sample of 561 self-identified Māori collected as part of the New Zealand Attitudes and Values Study. As predicted, our analyses indicated that self-reported appearance as Māori, or the extent to which people thought they personally displayed features which visibly identified them as Māori to others, significantly predicted decreased rates of home ownership. This association held when adjusting for numerous demographic covariates, such as education, level of deprivation of the immediate area, household income, age, relationship status, region of residence, and so forth. Our analyses suggest there is, or at least has been in the recent past, institutional racism against Māori in New Zealand's home lending industry based on merely appearing more Māori.

The prevalence of symptoms of depression and anxiety, and the level of life stress and worry in New Zealand Māori and non-Māori women in late pregnancy.

PubMed

Signal, T Leigh; Paine, Sarah-Jane; Sweeney, Bronwyn; Muller, Diane; Priston, Monique; Lee, Kathryn; Gander, Philippa; Huthwaite, Mark

2017-02-01

To describe the prevalence of symptoms of depression and anxiety, and the level of life stress and worry in late pregnancy for Māori and non-Māori women. In late pregnancy, women completed a questionnaire recording their prior history of mood disorders; self-reported current depressive symptoms (⩾13 on the Edinburgh Postnatal Depression Scale), current anxiety symptoms (⩾6 on the anxiety items from the Edinburgh Postnatal Depression Scale), significant life stress (⩾2 items on life stress scale) and dysfunctional worry (>12 on the Brief Measure of Worry Scale). Data were obtained from 406 Māori women (mean age = 27.6 years, standard deviation=6.3 years) and 738 non-Māori women (mean age = 31.6 years, standard deviation=5.3 years). Depressive symptoms (22% vs 15%), anxiety symptoms (25% vs 20%), significant life stress (55% vs 30%) and a period of poor mood during the current pregnancy (18% vs 14%) were more prevalent for Māori than non-Maori women. Less than 50% of women who had experienced ⩾2 weeks of poor mood during the current pregnancy had sought help. Being young was an independent risk factor for depressive symptoms, significant life stress and dysfunctional worry. A prior history of depression was also consistently associated with a greater risk of negative affect in pregnancy. Antenatal mental health requires at least as much attention and resourcing as mental health in the postpartum period. Services need to specifically target Māori women, young women and women with a prior history of depression.

Narratives of four Māori ex-inmates about their experiences and perspectives of rehabilitation programmes.

PubMed

Nakhid, Camille; Shorter, Lily Tairiri

2014-06-01

Māori are overrepresented in the criminal justice system in Aotearoa New Zealand. Māori offenders comprise 53% of those serving custodial sentences and 48% serving community-based sentences. The majority of Māori offenders reoffended within 2 years of serving their sentence. A number of programmes aimed at reducing recidivism among Māori have been implemented, and there is considerable debate around the effectiveness of these programmes. This qualitative study focuses on the narratives of four Māori male ex-inmates about their reoffending and their experiences of the rehabilitation programmes during their incarceration. Using a narrative approach, the study sought to hear the shared stories from the men and to determine what they believe would have reduced their reoffending. The stories revealed that a lack of financial resources and gang connections influenced reoffending; the value of prison rehabilitation programmes varied depending on their appropriateness to the inmate and to their intended outcomes; and healing programmes incorporating kaupapa Māori principles and practices assisted the participants in understanding their cultural heritage and communicating with society in more acceptable ways.

Applying Community-Based Participatory Research to Create a Diabetes Prevention Documentary with New Zealand Māori.

PubMed

Farmer, Alison; Gage, Jeffrey; Kirk, Ray; Edgar, Timothy

2016-01-01

Type 2 diabetes is almost three times more prevalent in the indigenous people of New Zealand (Māori) than non-Māori. Despite the high rate of diabetes in the Māori population, little is known about their personal understanding or experience of the disease. To engage Māori in a participatory process to develop a culturally relevant diabetes prevention documentary. Principles of community-based participatory research (CBPR) were applied to a qualitative research design employing key informant interviews and focus groups to develop a diabetes prevention documentary. A CBPR approach provides an appropriate model for enacting local action-oriented approaches in the creation of a documentary that reflects Māori cultural beliefs and practices.

ORBITAL AND PHYSICAL PROPERTIES OF THE σ Ori Aa, Ab, B TRIPLE SYSTEM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simón-Díaz, S.; Caballero, J. A.; Apellániz, J. Maíz

2015-02-01

We provide a complete characterization of the astrophysical properties of the σ Ori Aa, Ab, B hierarchical triple system and an improved set of orbital parameters for the highly eccentric σ Ori Aa, Ab spectroscopic binary. We compiled a spectroscopic data set comprising 90 high-resolution spectra covering a total time span of 1963 days. We applied the Lehman-Filhés method for a detailed orbital analysis of the radial velocity curves and performed a combined quantitative spectroscopic analysis of the σ Ori Aa, Ab, B system by means of the stellar atmosphere code FASTWIND. We used our own plus other available information onmore » photometry and distance to the system for measuring the radii, luminosities, and spectroscopic masses of the three components. We also inferred evolutionary masses and stellar ages using the Bayesian code BONNSAI. The orbital analysis of the new radial velocity curves led to a very accurate orbital solution of the σ Ori Aa, Ab pair. We provided indirect arguments indicating that σ Ori B is a fast-rotating early B dwarf. The FASTWIND+BONNSAI analysis showed that the Aa, Ab pair contains the hottest and most massive components of the triple system while σ Ori B is a bit cooler and less massive. The derived stellar ages of the inner pair are intriguingly younger than the one widely accepted for the σ Orionis cluster, at 3 ± 1 Ma. The outcome of this study will be of key importance for a precise determination of the distance to the σ Orionis cluster, the interpretation of the strong X-ray emission detected for σ Ori Aa, Ab, B, and the investigation of the formation and evolution of multiple massive stellar systems and substellar objects.« less

A STAR-FORMING RING AROUND κ Ori 250 pc FROM THE SUN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pillitteri, I.; Wolk, S. J.; Megeath, S. T., E-mail: ipillitt@cfa.harvard.edu

2016-04-01

X-rays are a powerful probe of activity in early stages of star formation. They allow us to identify young stars even after they have lost the IR signatures of circumstellar disks and provide constraints on their distance. Here, we report on XMM-Newton observations that detect 121 young stellar objects (YSOs) in two fields between L1641 S and κ Ori. These observations extend the Survey of Orion A with XMM and Spitzer (SOXS). The YSOs are contained in a ring of gas and dust apparent at millimeter wavelengths, and in far-IR and near-IR surveys. The X-ray luminosity function of the YSOs detectedmore » in the two fields indicates a distance of 250–280 pc, much closer than the Orion A cloud and similar to distance estimates of κ Ori. We propose that the ring is a 5–8 pc diameter shell that has been swept up by κ Ori. This ring contains several groups of stars detected by Spitzer and WISE including one surrounding the Herbig Ae/Be stars V1818 Ori. In this interpretation, the κ Ori ring is one of several shells swept up by massive stars within the Orion Eridanus Superbubble and is unrelated to the southern portion of Orion A/L1641 S.« less

Insanity and ethnicity in New Zealand: Māori encounters with the Auckland Mental Hospital, 1860-1900.

PubMed

Barry, Lorelle; Coleborne, Catharine

2011-09-01

This article examines Māori patients at the Auckland Mental Hospital between 1860 and 1900.We argue that the patient case notes reveal 'European' categories in which Māori were situated, and demonstrate the extent to which the authorities at the hospital grappled with their appearance, their language and their culture, all of which were elements of their ethnicity. We argue that the use of institutional case records is highly suggestive of some of the historical meanings of insanity for Māori, including the lack of detailed or sustained collection of information about patients' tribal affiliations, the interest shown in their rights to land in maintenance payment inquiries, the experiences of cultural alienation or mate Māori, and the sad outcomes for Māori.

[Depressor anguli oris sign (DAO) in facial paresis. How to search it and release the smile (technical note)].

PubMed

Labbé, D; Bénichou, L; Iodice, A; Giot, J-P

2012-06-01

After facial paralysis recovery, it is common to note a co-contraction between depressor anguli oris (DAO) muscle and zygomatic muscles. This DAO co-contraction will "obstruct" the patient's smile. The purpose of this technical note is to show how to find the DAO sign and how to free up the smile. TECHNICAL: This co-contraction between the zygomatic muscles and DAO research is placing a finger on marionette line, asking the patient to smile: we perceive a rope under the skin corresponding to the abnormal contraction and powerful DAO. A diagnostic test with lidocaine injection into the DAO can be performed to confirm the diagnosis. The treatment of pathological DAO's contraction can be by injection of botulinum toxin in the DAO, or by surgical myectomy. In all cases, a speech therapy complete the treatment. The DAO sign is a semiological entity easy to find. His treatment releases smile without negative effect on the facial expression as the DAO is especially useful in the expression of disgust. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

The Minimal Replicator of Epstein-Barr Virus oriP

PubMed Central

Yates, John L.; Camiolo, Sarah M.; Bashaw, Jacqueline M.

2000-01-01

oriP is a 1.7-kb region of the Epstein-Barr virus (EBV) chromosome that supports the replication and stable maintenance of plasmids in human cells. oriP contains two essential components, called the DS and the FR, both of which contain multiple binding sites for the EBV-encoded protein, EBNA-1. The DS appears to function as the replicator of oriP, while the FR acts in conjunction with EBNA-1 to prevent the loss of plasmids from proliferating cells. Because of EBNA-1's role in stabilizing plasmids through the FR, it has not been entirely clear to what extent EBNA-1 might be required for replication from oriP per se, and a recent study has questioned whether EBNA-1 has any direct role in replication. In the present study we found that plasmids carrying oriP required EBNA-1 to replicate efficiently even when assayed only 2 days after plasmids were introduced into the cell lines 143B and 293. Significantly, using 293 cells it was demonstrated that the plasmid-retention function of EBNA-1 and the FR did not contribute significantly to the accumulation of replicated plasmids, and the DS supported efficient EBNA-1-dependent replication in the absence of the FR. The DS contains two pairs of closely spaced EBNA-1 binding sites, and a previous study had shown that both sites within either pair are required for activity. However, it was unclear from previous work what additional sequences within the DS might be required. We found that each “half” of the DS, including a pair of closely spaced EBNA-1 binding sites, had significant replicator activity when the other half had been deleted. The only significant DNA sequences that the two halves of the DS share in common, other than EBNA-1 binding sites, is a 9-bp sequence that is present twice in the “left half” and once in the “right half.” These nonamer repeats, while not essential for activity, contributed significantly to the activity of each half of the DS. Two thymines occur at unique positions within EBNA-1

A qualitative Kaupapa Māori approach to understanding infant and young child feeding practices of Māori and Pacific grandparents in Auckland, New Zealand.

PubMed

Tapera, Rachel; Harwood, Matire; Anderson, Anneka

2017-04-01

The present research sought to better understand the barriers, facilitators, attitudes and beliefs that influence the way Māori and Samoan grandparents feed their grandchildren in a deprived urban neighbourhood in New Zealand. The research adopted a qualitative methodology that was consistent with a Kaupapa Māori research approach. Seven semi-structured interviews were conducted with grandparents to collect narrative data. Sampling occurred in one Auckland suburb. The suburb was selected because of its high level of socio-economic deprivation and ethnic diversity. Seven grandparents participated in the study (five Māori and two Samoan). Each participant met the inclusion criteria (i.e. they had provided at least five meals per week over the previous three months to grandchildren aged less than 24 months). Marae (i.e. meeting houses and areas used by local Māori tribes/sub-tribes) and community organisations were used to recruit participants. A general inductive thematic analysis identified four key themes: (i) grandparents' understanding of optimal feeding practices; (ii) economic and material factors; (iii) previous experiences and customary norms; and (iv) social support and societal pressure. The study showed that grandparents' complementary feeding practices in caring for infant grandchildren were influenced by upstream structural elements such as government policies related to welfare and pensions, employment, income and cultural knowledge. Frameworks that seek to achieve social justice and support cultural practices should be employed and promoted in the development of future policy and research in this area.

Volunteering predicts happiness among older Māori and non-Māori in the New Zealand health, work, and retirement longitudinal study.

PubMed

Dulin, Patrick L; Gavala, Jhanitra; Stephens, Christine; Kostick, Marylynne; McDonald, Jennifer

2012-01-01

This study sought to understand the relationship between volunteer activity and happiness among a sample of older adult New Zealanders. It specifically sought to determine if ethnicity (Māori vs. non-Māori) and economic living standards (ELS) functioned as moderators of the relationship between volunteering and happiness. Data were garnered from the 2008 administration of the New Zealand Health, Work, and Retirement Longitudinal Study. Correlational and multiple regression procedures were employed to examine study hypotheses. Results from multiple regression analyses showed that the amount of volunteering per week was a unique predictor of the overall level of happiness. Moderation analyses indicated that ethnicity did not function as a moderator of the relationship between volunteering and happiness, but ELS did. Those with low ELS evidenced a stronger relationship between volunteering and happiness than those with high ELS. Results also indicated that Maori and those with low ELS volunteered more frequently than non-Māori and those with high ELS. This study provides evidence that volunteering is related to increased happiness, irrespective of ethnicity. It also provides further evidence that the relationship between volunteering and happiness is moderated by economic resources. Older individuals at the low end of the economic spectrum are likely to benefit more from volunteering than those at the high end.

The effectiveness of television advertising campaigns on generating calls to a national Quitline by Māori.

PubMed

Wilson, N; Grigg, M; Graham, L; Cameron, G

2005-08-01

To examine the effectiveness of four mass media campaigns on calls to a national Quitline by Māori (the indigenous people of New Zealand). Monthly Quitline call data and calls within one hour of a television commercial (TVC) being shown were analysed for the 2002-2003 period. Data on target audience rating points (TARPs) and expenditure on TVCs were also used (n = 2319 TVC placements). Māori were found to register with the Quitline at higher rates during the most intense six campaign months (15% more registrations compared to less intense months). The most effective campaign generated 115 calls per 100 TARPs by Māori callers within one hour of TVC airing (the "Every cigarette" campaign). A more Māori orientated campaign with both health and cultural themes generated 91 calls per 100 TARPs from Māori callers. For these two campaigns combined, the advertising cost per new registration with the Quitline by a Māori caller was NZD 30-48. Two second hand smoke campaigns that did not show the Quitline number were much less effective at 25 and 45 calls per 100 TARPs. These television advertising campaigns were effective and cost effective in generating calls to a national Quitline by Māori. Health authorities should continue to explore the use of both "threat appeal" style media campaigns and culturally appropriate campaigns to support Quitline use by indigenous peoples.

Understanding the role of culture in pain: Māori practitioner perspectives of pain descriptors.

PubMed

Magnusson, Jane E; Fennell, Joyce A

2011-01-21

There is growing interest in the role of cultural diversity within healthcare settings yet minority ethnic groups are underrepresented in the healthcare literature, including the literature on pain. To better assess and treat pain in different cultures the perspectives and experiences of that culture must be taken into consideration and therefore the present study was undertaken to better understand Māori perspectives of pain. Māori healthcare providers and kaumātua (tribal leaders/elders) completed questionnaires relating to the experience of pain and were asked to provide feedback regarding the suitability of words and phrases typically used to describe symptoms of pain and pain-related disability. Participants were also asked to provide words, or phrases (in te reo Māori or English) representing characteristics of pain which had not been provided but would be useful in the assessment of pain in a Māori population. All of the pain descriptors, and 92% of the phrases regarding the experience of pain, provided were endorsed by the majority of participants demonstrating that, as in many cultures, Māori perceive pain as a multidimensional experience impacting them on physiological, psychological, and social dimensions and that the terms and phrases of measures commonly used to assess pain appropriately capture their pain experiences. The implications of these findings are that established measures can be used when assessing pain in Māori. However, it is beneficial to confirm that the descriptors used in those measures accurately capture the experiences being measured.

Defects in oxygen supply to skeletal muscle of prediabetic ZDF rats

PubMed Central

Goldman, Daniel; Hanson, Madelyn; Stephenson, Alan H.; Milkovich, Stephanie; Benlamri, Amina; Ellsworth, Mary L.; Sprague, Randy S.

2010-01-01

In humans, prediabetes is characterized by marked increases in plasma insulin and near normal blood glucose levels as well as microvascular dysfunction of unknown origin. Using the extensor digitorum longus muscle of 7-wk inbred male Zucker diabetic fatty rats fed a high-fat diet as a model of prediabetes, we tested the hypothesis that hyperinsulinemia contributes to impaired O2 delivery in skeletal muscle. Using in vivo video microscopy, we determined that the total O2 supply to capillaries in the extensor digitorum longus muscle of prediabetic rats was reduced to 64% of controls with a lower O2 supply rate per capillary and higher O2 extraction resulting in a decreased O2 saturation at the venous end of the capillary network. These findings suggest a lower average tissue Po2 in prediabetic animals. In addition, we determined that insulin, at concentrations measured in humans and Zucker diabetic fatty rats with prediabetes, inhibited the O2-dependent release of ATP from rat red blood cells (RBCs). This inability to release ATP could contribute to the impaired O2 delivery observed in rats with prediabetes, especially in light of the finding that the endothelium-dependent relaxation of resistance arteries from these animals is not different from controls and is not altered by insulin. Computational modeling confirmed a significant 8.3-mmHg decrease in average tissue Po2 as well as an increase in the heterogeneity of tissue Po2, implicating a failure of a regulatory system for O2 supply. The finding that insulin attenuates the O2-dependent release of ATP from RBCs suggests that this defect in RBC physiology could contribute to a failure in the regulation of O2 supply to meet the demand in skeletal muscle in prediabetes. PMID:20207810

Cultural health literacy: the experiences of Māori in palliative care.

PubMed

Kidd, Jacquie; Black, Stella; Blundell, Rawiri; Peni, Tamati

2018-05-01

Health literacy is a concept that is frequently applied to the patient's ability to find and comprehend health information. However, recent literature has included the skill of the health professional and the accessibility of health resources as important factors in the level of health literacy achieved by individuals and populations. In 2014 a qualitative study undertaken in Aotearoa New Zealand, investigated the context of health literacy for Māori in a palliative care setting (Māori are the indigenous people of Aotearoa New Zealand). The study included the experiences of patients, whānau (families), and health professionals. Individual semi-structured interviews were held with 21 patients, whānau and six key informants: a medical specialist, a service leader involved in developing culturally specific responses to patients, two Māori service managers, and two Māori health team leaders. Focus groups were held with a total of 54 health professionals providing palliative care services. A thematic analysis was undertaken using a general inductive approach. The trustworthiness and reliability of the analysis was supported by sharing analysis of the transcripts among the research team. Member checking or respondent validation was used in seeking confirmation of the interim findings at five hui (meetings) with the research communities involved. This study found that the shock and grief that attends a life-limiting illness made hearing and processing health information very difficult for patients and whānau. Further, 'hard conversations' about moving from active treatment to palliative care were often avoided by health professionals, leaving patients and whānau distressed and confused about their choices and prognosis. Finally, poor cultural health literacy on the part of organisations has likely impacted on late access to or avoidance of palliative care for Māori.

Volumetric muscle loss injury repair using in situ fibrin gel cast seeded with muscle-derived stem cells (MDSCs)

PubMed Central

Matthias, Nadine; Hunt, Samuel D.; Wu, Jianbo; Lo, Jonathan; Smith Callahan, Laura A.; Li, Yong; Huard, Johnny; Darabi, Radbod

2018-01-01

Volumetric muscle defect, caused by trauma or combat injuries, is a major health concern leading to severe morbidity. It is characterized by partial or full thickness loss of muscle and its bio-scaffold, resulting in extensive fibrosis and scar formation. Therefore, the ideal therapeutic option is to use stem cells combined with bio-scaffolds to restore muscle. For this purpose, muscle-derived stem cells (MDSCs) are a great candidate due to their unique multi-lineage differentiation potential. In this study, we evaluated the regeneration potential of MDSCs for muscle loss repair using a novel in situ fibrin gel casting. Muscle defect was created by a partial thickness wedge resection in the tibialis anterior (TA)muscles of NSG mice which created an average of 25% mass loss. If untreated, this defect leads to severe muscle fibrosis. Next, MDSCs were delivered using a novel in situ fibrin gel casting method. Our results demonstrated MDSCs are able to engraft and form new myofibers in the defect when casted along with fibrin gel. LacZ labeled MDSCs were able to differentiate efficiently into new myofibers and significantly increase muscle mass. This was also accompanied by significant reduction of fibrotic tissue in the engrafted muscles. Furthermore, transplanted cells also contributed to new vessel formation and satellite cell seeding. These results confirmed the therapeutic potential of MDSCs and feasibility of direct in situ casting of fibrin/MDSC mixture to repair muscle mass defects. PMID:29331939

Quantitative Magnetic Resonance Imaging Volumetry of Facial Muscles in Healthy Patients with Facial Palsy

PubMed Central

Volk, Gerd F.; Karamyan, Inna; Klingner, Carsten M.; Reichenbach, Jürgen R.

2014-01-01

Background: Magnetic resonance imaging (MRI) has not yet been established systematically to detect structural muscular changes after facial nerve lesion. The purpose of this pilot study was to investigate quantitative assessment of MRI muscle volume data for facial muscles. Methods: Ten healthy subjects and 5 patients with facial palsy were recruited. Using manual or semiautomatic segmentation of 3T MRI, volume measurements were performed for the frontal, procerus, risorius, corrugator supercilii, orbicularis oculi, nasalis, zygomaticus major, zygomaticus minor, levator labii superioris, orbicularis oris, depressor anguli oris, depressor labii inferioris, and mentalis, as well as for the masseter and temporalis as masticatory muscles for control. Results: All muscles except the frontal (identification in 4/10 volunteers), procerus (4/10), risorius (6/10), and zygomaticus minor (8/10) were identified in all volunteers. Sex or age effects were not seen (all P > 0.05). There was no facial asymmetry with exception of the zygomaticus major (larger on the left side; P = 0.012). The exploratory examination of 5 patients revealed considerably smaller muscle volumes on the palsy side 2 months after facial injury. One patient with chronic palsy showed substantial muscle volume decrease, which also occurred in another patient with incomplete chronic palsy restricted to the involved facial area. Facial nerve reconstruction led to mixed results of decreased but also increased muscle volumes on the palsy side compared with the healthy side. Conclusions: First systematic quantitative MRI volume measures of 5 different clinical presentations of facial paralysis are provided. PMID:25289366

Poor repair of skeletal muscle in aging mice reflects a defect in local, interleukin-33-dependent, accumulation of regulatory T cells

PubMed Central

Kuswanto, Wilson; Burzyn, Dalia; Panduro, Marisella; Wang, Kathy K.; Jang, Young Charles; Wagers, Amy J.; Benoist, Christophe; Mathis, Diane

2016-01-01

SUMMARY Normal repair of skeletal muscle requires local expansion of a special population of Foxp3+CD4+ regulatory T (Treg) cells. Such cells failed to accumulate in acutely injured muscle of old mice, known to undergo ineffectual repair. This defect reflected reduced recruitment of Treg cells to injured muscle, as well as less proliferation and retention therein. Interleukin (IL)-33 regulated muscle Treg cell homeostasis in young mice, and its administration to old mice ameliorated their deficits in Treg cell accumulation and muscle regeneration. The major IL-33-expressing cells in skeletal muscle displayed a constellation of markers diagnostic of fibro/adipogenic progenitor cells, and were often associated with neural structures, including nerve fibers, nerve bundles and muscle spindles, which are stretch-sensitive mechanoreceptors important for proprioception. IL-33+ cells were more frequent after muscle injury, and were reduced in old mice. IL-33 is well situated to relay signals between the nervous and immune systems within the muscle context. PMID:26872699

42 CFR 93.402 - ORI allegation assessments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false ORI allegation assessments. 93.402 Section 93.402 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON...

oriTfinder: a web-based tool for the identification of origin of transfers in DNA sequences of bacterial mobile genetic elements.

PubMed

Li, Xiaobin; Xie, Yingzhou; Liu, Meng; Tai, Cui; Sun, Jingyong; Deng, Zixin; Ou, Hong-Yu

2018-05-04

oriTfinder is a web server that facilitates the rapid identification of the origin of transfer site (oriT) of a conjugative plasmid or chromosome-borne integrative and conjugative element. The utilized back-end database oriTDB was built upon more than one thousand known oriT regions of bacterial mobile genetic elements (MGEs) as well as the known MGE-encoding relaxases and type IV coupling proteins (T4CP). With a combination of similarity searches for the oriTDB-archived oriT nucleotide sequences and the co-localization of the flanking relaxase homologous genes, the oriTfinder can predict the oriT region with high accuracy in the DNA sequence of a bacterial plasmid or chromosome in minutes. The server also detects the other transfer-related modules, including the potential relaxase gene, T4CP gene and the type IV secretion system gene cluster, and the putative genes coding for virulence factors and acquired antibiotic resistance determinants. oriTfinder may contribute to meeting the increasing demands of re-annotations for bacterial conjugative, mobilizable or non-transferable elements and aid in the rapid risk accession of disease-relevant trait dissemination in pathogenic bacteria of interest. oriTfinder is freely available to all users without any login requirement at http://bioinfo-mml.sjtu.edu.cn/oriTfinder.

Indigenous Māori perspectives on urban transport patterns linked to health and wellbeing.

PubMed

Raerino Ngāti Awa Te Arawa, K; Macmillan, Alex K; Jones Ngāti Kahungunu, Rhys G

2013-09-01

There is a growing body of research linking urban transport systems to inequities in health. However, there is a lack of research providing evidence of the effect of transport systems on indigenous family wellbeing. We examined the connections between urban transport and the health and wellbeing of Māori, the indigenous people of New Zealand. We provide an indigenous exploration of current urban transport systems, with a particular focus on the impacts of car dependence and the need for culturally relevant travel. We interviewed nineteen Māori participants utilising qualitative research techniques underpinned by an indigenous research methodology (Kaupapa Māori). The data highlighted the importance of accessing cultural activities and sites relevant to 'being Māori', and issues with affordability and safety of public transport. Understanding the relationship between indigenous wellbeing and transport systems that goes further than limited discourses of inequity is essential to improving transport for indigenous wellbeing. Providing an indigenous voice in transport decision-making will make it more likely that indigenous health and wellbeing is prioritised in transport planning. Copyright © 2013. Published by Elsevier Ltd.

The effectiveness of television advertising campaigns on generating calls to a national Quitline by Māori

PubMed Central

Wilson, N; Grigg, M; Graham, L; Cameron, G

2005-01-01

Methods: Monthly Quitline call data and calls within one hour of a television commercial (TVC) being shown were analysed for the 2002–2003 period. Data on target audience rating points (TARPs) and expenditure on TVCs were also used (n = 2319 TVC placements). Results: Māori were found to register with the Quitline at higher rates during the most intense six campaign months (15% more registrations compared to less intense months). The most effective campaign generated 115 calls per 100 TARPs by Māori callers within one hour of TVC airing (the "Every cigarette" campaign). A more Māori orientated campaign with both health and cultural themes generated 91 calls per 100 TARPs from Māori callers. For these two campaigns combined, the advertising cost per new registration with the Quitline by a Māori caller was $NZ30–48. Two second hand smoke campaigns that did not show the Quitline number were much less effective at 25 and 45 calls per 100 TARPs. Conclusions: These television advertising campaigns were effective and cost effective in generating calls to a national Quitline by Māori. Health authorities should continue to explore the use of both "threat appeal" style media campaigns and culturally appropriate campaigns to support Quitline use by indigenous peoples. PMID:16046693

Volumetric muscle loss injury repair using in situ fibrin gel cast seeded with muscle-derived stem cells (MDSCs).

PubMed

Matthias, Nadine; Hunt, Samuel D; Wu, Jianbo; Lo, Jonathan; Smith Callahan, Laura A; Li, Yong; Huard, Johnny; Darabi, Radbod

2018-03-01

Volumetric muscle defect, caused by trauma or combat injuries, is a major health concern leading to severe morbidity. It is characterized by partial or full thickness loss of muscle and its bio-scaffold, resulting in extensive fibrosis and scar formation. Therefore, the ideal therapeutic option is to use stem cells combined with bio-scaffolds to restore muscle. For this purpose, muscle-derived stem cells (MDSCs) are a great candidate due to their unique multi-lineage differentiation potential. In this study, we evaluated the regeneration potential of MDSCs for muscle loss repair using a novel in situ fibrin gel casting. Muscle defect was created by a partial thickness wedge resection in the tibialis anterior (TA) muscles of NSG mice which created an average of 25% mass loss. If untreated, this defect leads to severe muscle fibrosis. Next, MDSCs were delivered using a novel in situ fibrin gel casting method. Our results demonstrated MDSCs are able to engraft and form new myofibers in the defect when casted along with fibrin gel. LacZ labeled MDSCs were able to differentiate efficiently into new myofibers and significantly increase muscle mass. This was also accompanied by significant reduction of fibrotic tissue in the engrafted muscles. Furthermore, transplanted cells also contributed to new vessel formation and satellite cell seeding. These results confirmed the therapeutic potential of MDSCs and feasibility of direct in situ casting of fibrin/MDSC mixture to repair muscle mass defects. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Prevalence of mental disorders among Māori in Te Rau Hinengaro: the New Zealand Mental Health Survey.

PubMed

Baxter, Joanne; Kingi, Te Kani; Tapsell, Rees; Durie, Mason; McGee, Magnus A

2006-10-01

To describe the prevalence of mental disorders (period prevalence across aggregated disorders, 12 month and lifetime prevalence) among Māori in Te Rau Hinengaro: The New Zealand Mental Health Survey. Te Rau Hinengaro: The New Zealand Mental Health Survey, undertaken between 2003 and 2004, was a nationally representative face-to-face household survey of 12,992 New Zealand adults aged 16 years and over, including 2,595 Māori. Ethnicity was measured using the 2001 New Zealand census ethnicity question. A fully structured diagnostic interview, the World Health Organization World Mental Health Survey Initiative version of the Composite International Diagnostic Interview (CIDI 3.0), was used to measure disorder. The overall response rate was 73.3%. This paper presents selected findings for the level and pattern of mental disorder prevalence among Māori. Māori lifetime prevalence of any disorder was 50.7%, 12 month prevalence 29.5% and 1 month prevalence 18.3%. The most common 12 month disorders were anxiety (19.4%), mood (11.4%) and substance (8.6%) disorders and the most common lifetime disorders were anxiety (31.3%), substance (26.5%) and mood (24.3%) disorders. Levels of lifetime comorbidity were high with 12 month prevalence showing 16.4% of Māori with one disorder, 7.6% with two disorders and 5.5% with three or more disorders. Twelve-month disorders were more common in Māori females than in males (33.6%vs 24.8%) and in younger age groups: 16-24 years, 33.2%; 25-44 years, 32.9%; 45-64 years, 23.7%; and 65 years and over, 7.9%. Disorder prevalence was greatest among Māori with the lowest equivalized household income and least education. However, differences by urbanicity and region were not significant. Of Māori with any 12 month disorder, 29.6% had serious, 42.6% had moderate and 27.8% had mild disorders. Mental disorders overall and specific disorder groups (anxiety, mood and substance) are common among Māori and measures of severity indicate that disorders

Pathways to ambulatory sensitive hospitalisations for Māori in the Auckland and Waitemata regions.

PubMed

Barker, Carol; Crengle, Sue; Bramley, Dale; Bartholomew, Karen; Bolton, Patricia; Walsh, Michael; Wignall, Jean

2016-10-28

Ambulatory Sensitive Hospitalisations (ASH) are a group of conditions potentially preventable through interventions delivered in the primary health care setting. ASH rates are consistently higher for Māori compared with non-Māori. This study aimed to establish Māori experience of factors driving the use of hospital services for ASH conditions, including barriers to accessing primary care. A telephone questionnaire exploring pathways to ASH was administered to Māori (n=150) admitted to Auckland and Waitemata District Health Board (DHB) hospitals with an ASH condition between January 1st-June 30th 2015. A cohort of 1,013 participants were identified; 842 (83.1%) were unable to be contacted. Of the 171 people contactable, 150 agreed to participate, giving an overall response rate of 14.8% and response rate of contactable patients of 87.7%. Results demonstrated high rates of self-reported enrolment, utilisation and preference for primary care. Many participants demonstrated appropriate health seeking behaviour and accurate recall of diagnoses. While financial barriers to accessing primary care were reported, non-financial barriers including lack of after-hours provision (12.6% adults, 37.7% children), appointment availability (7.4% adults, 17.0% children) and lack of transport (13.7% adults, 20.8% children) also featured in participant responses. Interventions to reduce Māori ASH include: timely access to primary care through electronic communications, increased appointment availability, extended opening hours, low cost after-hours care and consistent best management of ASH conditions in general practice through clinical pathways. Facilitated enrolment of ASH patients with no general practitioner could also reduce ASH. Research into transport barriers and enablers for Māori accessing primary care is required to support future interventions.

VCP-dependent muscle degeneration is linked to defects in a dynamic tubular lysosomal network in vivo

PubMed Central

Johnson, Alyssa E; Shu, Huidy; Hauswirth, Anna G; Tong, Amy; Davis, Graeme W

2015-01-01

Lysosomes are classically viewed as vesicular structures to which cargos are delivered for degradation. Here, we identify a network of dynamic, tubular lysosomes that extends throughout Drosophila muscle, in vivo. Live imaging reveals that autophagosomes merge with tubular lysosomes and that lysosomal membranes undergo extension, retraction, fusion and fission. The dynamics and integrity of this tubular lysosomal network requires VCP, an AAA-ATPase that, when mutated, causes degenerative diseases of muscle, bone and neurons. We show that human VCP rescues the defects caused by loss of Drosophila VCP and overexpression of disease relevant VCP transgenes dismantles tubular lysosomes, linking tubular lysosome dysfunction to human VCP-related diseases. Finally, disruption of tubular lysosomes correlates with impaired autophagosome-lysosome fusion, increased cytoplasmic poly-ubiquitin aggregates, lipofuscin material, damaged mitochondria and impaired muscle function. We propose that VCP sustains sarcoplasmic proteostasis, in part, by controlling the integrity of a dynamic tubular lysosomal network. DOI: http://dx.doi.org/10.7554/eLife.07366.001 PMID:26167652

Dietary intakes of Pacific, Māori, Asian and European adolescents: the Auckland High School Heart Survey.

PubMed

Sluyter, John D; Schaaf, David; Metcalf, Patricia A; Scragg, Robert K R

2010-02-01

To compare dietary intakes of European, Māori, Pacific Island and Asian adolescents living in Auckland. A self-administered food frequency questionnaire was used to assess daily nutrient intakes of 2,549 14- to 21-year-old high-school students in Auckland (1,422 male and 1,127 female) in a cross-sectional survey carried out between 1997 and 1998. Compared with Europeans, Māori and Pacific Islanders consumed more energy per day. Carbohydrate, protein and fat intakes were higher in Māori and Pacific Islanders than in Europeans. Cholesterol intakes were lowest in Europeans and alcohol intakes were highest in Europeans and Māori. When nutrient intakes were expressed as their percentage contribution to total energy, many ethnic differences in nutrient intakes between Europeans and Māori or Pacific Islanders were eliminated. After adjustment for energy intake and age, Europeans ate the fewest eggs, and Pacific Islanders and Asians ate more servings of chicken and fish, and fewer servings of milk and cereal than Europeans. Compared to Europeans, Pacific Islanders consumed larger portion sizes for nearly every food item. There were marked differences in nutrient intakes between Pacific, Māori, Asian and European adolescents. Ethnic differences in food selections, frequency of food servings and portion sizes contribute to the differences in nutrient intakes between these ethnic groups. These differences generally matched those of other studies in children and adults from these ethnic groups. Interventions that reduce frequency of food consumption and serving sizes and promote less-fatty food choices in Māori and Pacific adolescents are needed. © 2010 The Authors. Journal Compilation © 2010 Public Health Association of Australia.

Neoliberalism and indigenous knowledge: Māori health research and the cultural politics of New Zealand's "National Science Challenges".

PubMed

Prussing, Erica; Newbury, Elizabeth

2016-02-01

In 2012-13 the Ministry of Business, Innovation and Employment (MBIE) in New Zealand rapidly implemented a major restructuring of national scientific research funding. The "National Science Challenges" (NSC) initiative aims to promote greater commercial applications of scientific knowledge, reflecting ongoing neoliberal reforms in New Zealand. Using the example of health research, we examine the NSC as a key moment in ongoing indigenous Māori advocacy against neoliberalization. NSC rhetoric and practice through 2013 moved to marginalize participation by Māori researchers, in part through constructing "Māori" and "science" as essentially separate arenas-yet at the same time appeared to recognize and value culturally distinctive forms of Māori knowledge. To contest this "neoliberal multiculturalism," Māori health researchers reasserted the validity of culturally distinctive knowledge, strategically appropriated NSC rhetoric, and marshalled political resources to protect Māori research infrastructure. By foregrounding scientific knowledge production as an arena of contestation over neoliberal values and priorities, and attending closely to how neoliberalizing tactics can include moves to acknowledge cultural diversity, this analysis poses new questions for social scientific study of global trends toward reconfiguring the production of knowledge about health. Study findings are drawn from textual analysis of MBIE documents about the NSC from 2012 to 2014, materials circulated by Māori researchers in the blogosphere in 2014, and ethnographic interviews conducted in 2013 with 17 Māori health researchers working at 7 sites that included university-based research centers, government agencies, and independent consultancies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Photometric variability in FU Ori and Z CMa as observed by MOST

NASA Astrophysics Data System (ADS)

Siwak, Michal; Rucinski, Slavek M.; Matthews, Jaymie M.; Kuschnig, Rainer; Guenther, David B.; Moffat, Anthony F. J.; Rowe, Jason F.; Sasselov, Dimitar; Weiss, Werner W.

2013-06-01

Photometric observations obtained by the MOST satellite were used to characterize optical small-scale variability of the young stars FU Ori and Z CMa. Wavelet analysis for FU Ori reveals the possible existence of several 2-9 d quasi-periodic features occurring nearly simultaneously; they may be interpreted as plasma parcels or other localized disc heterogeneities revolving at different Keplerian radii in the accretion disc. Their periods may shorten slowly which may be due to spiralling in of individual parcels towards the inner disc radius, estimated at 4.8 ± 0.2 R⊙. Analysis of additional multicolour data confirms the previously obtained relation between variations in the B - V colour index and the V magnitude. In contrast to the FU Ori results, the oscillation spectrum of Z CMa does not reveal any periodicities with the wavelet spectrum possibly dominated by outburst of the Herbig Be component.

The voyage to McDonalds--short and long-term factors in the etiology of obesity in Mäori children in Aotearoa.

PubMed

Gray, George

2003-09-01

In Aotearoa, it has been revealed that 14.7% of European adults are obese, compared with 27.5% for Mäori adults. It has been difficult to elucidate the recent trends in children and adolescents without large-scale population analysis, but a recent study of obesity in Auckland schoolchildren revealed a prevalence rate of 15.8% for Mäori children, compared with 8.6% for European children. This essay will review factors affecting the etiology of obesity in Mäori children. The classification of obesity will be examined before a discussion of short-term and long-term factors leading to obesity in this ethnic group. Measuring Obesity in Children It has been recommended that the BMI range for overweight in Mäori be increased to 27-32, and obesity a BMI greater than 32. Unfortunately though, there is no consensus among researchers and some studies may use the conventional obesity range of a BMI greater than 30 for both Mäori and non-Mäori children. Mäori disproportionately occupy low socioeconomic strata in Aotearoa. The significant discrepancy between obesity prevalence rates for Mäori and European children indicates that other factors are involved. Dietary fat intake, and by extension obesity, tend to be more prevalent for people in low socioeconomic groups, as numerous studies have shown. Therefore, the Mäori-European obesity discrepancy can be further explained by the discrepancy in socioeconomic status between these two groups, as national census data reveal that Mäori are disproportionately represented in all negative socioeconomic indices. However, for completeness, it is necessary to understand exactly why Mäori dominate these indices.

Mesoangioblasts of inclusion-body myositis: a twofold tool to study pathogenic mechanisms and enhance defective muscle regeneration.

PubMed

Morosetti, R; Gliubizzi, C; Broccolini, A; Sancricca, C; Mirabella, M

2011-06-01

Mesoangioblasts are a class of adult stem cells of mesoderm origin, potentially useful for the treatment of primitive myopathies of different etiology. Extensive in vitro and in vivo studies in animal models of muscular dystrophy have demonstrated the ability of mesoangioblast to repair skeletal muscle when injected intra-arterially. In a previous work we demonstrated that mesoangioblasts obtained from diagnostic muscle biopsies of IBM patients display a defective differentiation down skeletal muscle and this block can be corrected in vitro by transient MyoD transfection. We are currently investigating different pathways involved in mesoangioblasts skeletal muscle differentiation and exploring alternative stimulatory approaches not requiring extensive cell manipulation. This will allow to obtain safe, easy and efficient molecular or pharmacological modulation of pro-myogenic pathways in IBM mesoangioblasts. It is of crucial importance to identify factors (ie. cytokines, growth factors) produced by muscle or inflammatory cells and released in the surrounding milieu that are able to regulate the differentiation ability of IBM mesoangioblasts. To promote myogenic differentiation of endogenous mesoangioblasts in IBM muscle, the modulation of such target molecules selectively dysregulated would be a more handy approach to enhance muscle regeneration compared to transplantation techniques. Studies on the biological characteristics of IBM mesoangioblasts with their aberrant differentiation behavior, the signaling pathways possibly involved in their differentiation block and the possible strategies to overcome it in vivo, might provide new insights to better understand the etiopathogenesis of this crippling disorder and to identify molecular targets susceptible of therapeutic modulation.

Perceptions of New Zealand nutrition labels by Māori, Pacific and low-income shoppers.

PubMed

Signal, Louise; Lanumata, Tolotea; Robinson, Jo-Ani; Tavila, Aliitasi; Wilton, Jenny; Ni Mhurchu, Cliona

2008-07-01

In New Zealand the burden of nutrition-related disease is greatest among Māori, Pacific and low-income peoples. Nutrition labels have the potential to promote healthy food choices and eating behaviours. To date, there has been a noticeable lack of research among indigenous peoples, ethnic minorities and low-income populations regarding their perceptions, use and understanding of nutrition labels. Our aim was to evaluate perceptions of New Zealand nutrition labels by Māori, Pacific and low-income peoples and to explore improvements or alternatives to current labelling systems. Māori, Samoan and Tongan researchers recruited participants who were regular food shoppers. Six focus groups were conducted which involved 158 people in total: one Māori group, one Samoan, one Tongan, and three low-income groups. Māori, Pacific and low-income New Zealanders rarely use nutrition labels to assist them with their food purchases for a number of reasons, including lack of time to read labels, lack of understanding, shopping habits and relative absence of simple nutrition labels on the low-cost foods they purchase. Current New Zealand nutrition labels are not meeting the needs of those who need them most. Possible improvements include targeted social marketing and education campaigns, increasing the number of low-cost foods with voluntary nutrition labels, a reduction in the price of 'healthy' food, and consideration of an alternative mandatory nutrition labelling system that uses simple imagery like traffic lights.

The design and relevance of a computerized gamified depression therapy program for indigenous māori adolescents.

PubMed

Shepherd, Matthew; Fleming, Theresa; Lucassen, Mathijs; Stasiak, Karolina; Lambie, Ian; Merry, Sally N

2015-03-03

Depression is a major health issue among Māori indigenous adolescents, yet there has been little investigation into the relevance or effectiveness of psychological treatments for them. Further, consumer views are critical for engagement and adherence to therapy. However, there is little research regarding indigenous communities' opinions about psychological interventions for depression. The objective of this study was to conduct semistructured interviews with Māori (indigenous New Zealand) young people (taitamariki) and their families to find out their opinions of a prototype computerized cognitive behavioral therapy (cCBT) program called Smart, Positive, Active, Realistic, X-factor thoughts (SPARX), a free online computer game intended to help young persons with mild to moderate depression, feeling down, stress or anxiety. The program will teach them how to resolve their issues on their own using Cognitive Behavioural Therapy as psychotherapeutic approach. There were seven focus groups on the subject of the design and cultural relevance of SPARX that were held, with a total of 26 participants (19 taitamarki, 7 parents/caregivers, all Māori). There were five of the groups that were with whānau (family groups) (n=14), one group was with Māori teenage mothers (n=4), and one group was with taitamariki (n=8). The general inductive approach was used to analyze focus group data. SPARX computerized therapy has good face validity and is seen as potentially effective and appealing for Māori people. Cultural relevance was viewed as being important for the engagement of Māori young people with SPARX. Whānau are important for young peoples' well-being. Participants generated ideas for improving SPARX for Māori and for the inclusion of whānau in its delivery. SPARX computerized therapy had good face validity for indigenous young people and families. In general, Māori participants were positive about the SPARX prototype and considered it both appealing and applicable

ORNL’s ORiGAMI Uses Big Data to Help Solve Age-Old Medical Mysteries in Seconds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sukumar, Rangan

ORiGAMI is a tool for discovering and evaluating potentially interesting associations and creating novel hypothesis in medicine. ORiGAMI will help you “connect the dots” across 70 million knowledge nuggets published in 23 million papers in the medical literature.

Let's kōrero (talk): the practice and functions of reminiscing among mothers and children in Māori families.

PubMed

Reese, Elaine; Neha, Tia

2015-01-01

Māori adults recall earlier memories than New Zealand European or Chinese adults, highlighting the importance of memory in Māori culture. In this study, Māori preschool children and their mothers (N = 41) reminisced about a diverse range of past events, including everyday events, the child's birth, cultural rituals and the child's misbehaviour. Mothers also reported how frequently they discussed past events with their children, as well as their level of affiliation with Māori culture. Mothers who reported higher levels of cultural affiliation also reported reminiscing more frequently about a diverse range of past events. Mothers reminisced in more elaborative ways about everyday events with their children compared to birth stories, cultural rituals and misbehaviours. Maternal reminiscing about cultural rituals and misbehaviours, however, along with maternal reminiscing about everyday events and birth stories, were significantly correlated with children's memory across conversations. These results underscore the continued importance of reminiscing about culturally relevant events in Māori culture, and the newfound importance for Māori families of reminiscing about everyday events.

Multiple defects in muscle glycogen synthase activity contribute to reduced glycogen synthesis in non-insulin dependent diabetes mellitus.

PubMed Central

Thorburn, A W; Gumbiner, B; Bulacan, F; Brechtel, G; Henry, R R

1991-01-01

To define the mechanisms of impaired muscle glycogen synthase and reduced glycogen formation in non-insulin dependent diabetes mellitus (NIDDM), glycogen synthase activity was kinetically analyzed during the basal state and three glucose clamp studies (insulin approximately equal to 300, 700, and 33,400 pmol/liter) in eight matched nonobese NIDDM and eight control subjects. Muscle glycogen content was measured in the basal state and following clamps at insulin levels of 33,400 pmol/liter. NIDDM subjects had glucose uptake matched to controls in each clamp by raising serum glucose to 15-20 mmol/liter. The insulin concentration required to half-maximally activate glycogen synthase (ED50) was approximately fourfold greater for NIDDM than control subjects (1,004 +/- 264 vs. 257 +/- 110 pmol/liter, P less than 0.02) but the maximal insulin effect was similar. Total glycogen synthase activity was reduced approximately 38% and glycogen content was approximately 30% lower in NIDDM. A positive correlation was present between glycogen content and glycogen synthase activity (r = 0.51, P less than 0.01). In summary, defects in muscle glycogen synthase activity and reduced glycogen content are present in NIDDM. NIDDM subjects also have less total glycogen synthase activity consistent with reduced functional mass of the enzyme. These findings and the correlation between glycogen synthase activity and glycogen content support the theory that multiple defects in glycogen synthase activity combine to cause reduced glycogen formation in NIDDM. PMID:1899428

Whakawhanaungatanga: the importance of culturally meaningful connections to improve uptake of pulmonary rehabilitation by Māori with COPD - a qualitative study.

PubMed

Levack, William Mm; Jones, Bernadette; Grainger, Rebecca; Boland, Pauline; Brown, Melanie; Ingham, Tristram R

2016-01-01

Pulmonary rehabilitation is known to improve function and quality of life for people with chronic obstructive pulmonary disease (COPD). However, little research has been conducted on the influence of culture on experiences of pulmonary rehabilitation. This study examined factors influencing uptake of pulmonary rehabilitation by Māori with COPD in New Zealand. Grounded theory nested within kaupapa Māori methodology. Transcripts were analyzed from interviews and focus groups with 15 Māori and ten New Zealand non-Māori invited to attend pulmonary rehabilitation for COPD. Māori participants had either attended a mainstream hospital-based program, a community-based program designed "by Māori, for Māori", or had experienced both. Several factors influencing uptake of pulmonary rehabilitation were common to all participants regardless of ethnicity: 1) participants' past experiences (eg, of exercise; of health care systems), 2) attitudes and expectations, 3) access issues (eg, time, transport, and conflicting responsibilities), and 4) initial program experiences. These factors were moderated by the involvement of family and peers, interactions with health professionals, the way information on programs was presented, and by new illness events. For Māori, however, several additional factors were also identified relating to cultural experiences of pulmonary rehabilitation. In particular, Māori participants placed high value on whakawhanaungatanga: the making of culturally meaningful connections with others. Culturally appropriate communication and relationship building was deemed so important by some Māori participants that when it was absent, they felt strongly discouraged to attend pulmonary rehabilitation. Only the more holistic services offered a program in which they felt culturally safe and to which they were willing to return for ongoing rehabilitation. Lack of attention to cultural factors in the delivery of pulmonary rehabilitation may be a barrier to its

Reoxidation of the Thiol-Disulfide Oxidoreductase MdbA by a Bacterial Vitamin K Epoxide Reductase in the Biofilm-Forming Actinobacterium Actinomyces oris.

PubMed

Luong, Truc Thanh; Reardon-Robinson, Melissa E; Siegel, Sara D; Ton-That, Hung

2017-05-15

Posttranslocational protein folding in the Gram-positive biofilm-forming actinobacterium Actinomyces oris is mediated by a membrane-bound thiol-disulfide oxidoreductase named MdbA, which catalyzes oxidative folding of nascent polypeptides transported by the Sec translocon. Reoxidation of MdbA involves a bacterial v itamin K ep o xide r eductase (VKOR)-like protein that contains four cysteine residues, C93/C101 and C175/C178, with the latter forming a canonical CXXC thioredoxin-like motif; however, the mechanism of VKOR-mediated reoxidation of MdbA is not known. We present here a topological view of the A. oris membrane-spanning protein VKOR with these four exoplasmic cysteine residues that participate in MdbA reoxidation. Like deletion of the VKOR gene, alanine replacement of individual cysteine residues abrogated polymicrobial interactions and biofilm formation, concomitant with the failure to form adhesive pili on the bacterial surface. Intriguingly, the mutation of the cysteine at position 101 to alanine (C101A mutation) resulted in a high-molecular-weight complex that was positive for MdbA and VKOR by immunoblotting and was absent in other alanine substitution mutants and the C93A C101A double mutation and after treatment with the reducing agent β-mercaptoethanol. Consistent with this observation, affinity purification followed by immunoblotting confirmed this MdbA-VKOR complex in the C101A mutant. Furthermore, ectopic expression of the Mycobacterium tuberculosis VKOR analog in the A. oris VKOR deletion (ΔVKOR) mutant rescued its defects, in contrast to the expression of M. tuberculosis VKOR variants known to be nonfunctional in the disulfide relay that mediates reoxidation of the disulfide bond-forming catalyst DsbA in Escherichia coli Altogether, the results support a model of a disulfide relay, from its start with the pair C93/C101 to the C175-X-X-C178 motif, that is required for MdbA reoxidation and appears to be conserved in members of the class

The lytic origin of herpesvirus papio is highly homologous to Epstein-Barr virus ori-Lyt: evolutionary conservation of transcriptional activation and replication signals.

PubMed Central

Ryon, J J; Fixman, E D; Houchens, C; Zong, J; Lieberman, P M; Chang, Y N; Hayward, G S; Hayward, S D

1993-01-01

Herpesvirus papio (HVP) is a B-lymphotropic baboon virus with an estimated 40% homology to Epstein-Barr virus (EBV). We have cloned and sequenced ori-Lyt of herpesvirus papio and found a striking degree of nucleotide homology (89%) with ori-Lyt of EBV. Transcriptional elements form an integral part of EBV ori-Lyt. The promoter and enhancer domains of EBV ori-Lyt are conserved in herpesvirus papio. The EBV ori-Lyt promoter contains four binding sites for the EBV lytic cycle transactivator Zta, and the enhancer includes one Zta and two Rta response elements. All five of the Zta response elements and one of the Rta motifs are conserved in HVP ori-Lyt, and the HVP DS-L leftward promoter and the enhancer were activated in transient transfection assays by the EBV Zta and Rta transactivators. The EBV ori-Lyt enhancer contains a palindromic sequence, GGTCAGCTGACC, centered on a PvuII restriction site. This sequence, with a single base change, is also present in the HVP ori-Lyt enhancer. DNase I footprinting demonstrated that the PvuII sequence was bound by a protein present in a Raji nuclear extract. Mobility shift and competition assays using oligonucleotide probes identified this sequence as a binding site for the cellular transcription factor MLTF. Mutagenesis of the binding site indicated that MLTF contributes significantly to the constitutive activity of the ori-Lyt enhancer. The high degree of conservation of cis-acting signal sequences in HVP ori-Lyt was further emphasized by the finding that an HVP ori-Lyt-containing plasmid was replicated in Vero cells by a set of cotransfected EBV replication genes. The central domain of EBV ori-Lyt contains two related AT-rich palindromes, one of which is partially duplicated in the HVP sequence. The AT-rich palindromes are functionally important cis-acting motifs. Deletion of these palindromes severely diminished replication of an ori-Lyt target plasmid. Images PMID:8389916

Risk of stomach cancer in Aotearoa/New Zealand: A Māori population based case-control study

PubMed Central

Sporle, Andrew; Corbin, Marine; Cheng, Soo; Harawira, Pauline; Gray, Michelle; Whaanga, Tracey; Guilford, Parry; Koea, Jonathan; Pearce, Neil

2017-01-01

Māori, the indigenous people of New Zealand, experience disproportionate rates of stomach cancer, compared to non-Māori. The overall aim of the study was to better understand the reasons for the considerable excess of stomach cancer in Māori and to identify priorities for prevention. Māori stomach cancer cases from the New Zealand Cancer Registry between 1 February 2009 and 31 October 2013 and Māori controls, randomly selected from the New Zealand electoral roll were matched by 5-year age bands to cases. Logistic regression was used to estimate odd ratios (OR) and 95% confidence intervals (CI) between exposures and stomach cancer risk. Post-stratification weighting of controls was used to account for differential non-response by deprivation category. The study comprised 165 cases and 480 controls. Nearly half (47.9%) of cases were of the diffuse subtype. There were differences in the distribution of risk factors between cases and controls. Of interest were the strong relationships seen with increased stomach risk and having >2 people sharing a bedroom in childhood (OR 3.30, 95%CI 1.95–5.59), testing for H pylori (OR 12.17, 95%CI 6.15–24.08), being an ex-smoker (OR 2.26, 95%CI 1.44–3.54) and exposure to environmental tobacco smoke in adulthood (OR 3.29, 95%CI 1.94–5.59). Some results were attenuated following post-stratification weighting. This is the first national study of stomach cancer in any indigenous population and the first Māori-only population-based study of stomach cancer undertaken in New Zealand. We emphasize caution in interpreting the findings given the possibility of selection bias. Population-level strategies to reduce the incidence of stomach cancer in Māori include expanding measures to screen and treat those infected with H pylori and a continued policy focus on reducing tobacco consumption and uptake. PMID:28732086

A muscle stem cell for every muscle: variability of satellite cell biology among different muscle groups

PubMed Central

Randolph, Matthew E.; Pavlath, Grace K.

2015-01-01

The human body contains approximately 640 individual skeletal muscles. Despite the fact that all of these muscles are composed of striated muscle tissue, the biology of these muscles and their associated muscle stem cell populations are quite diverse. Skeletal muscles are affected differentially by various muscular dystrophies (MDs), such that certain genetic mutations specifically alter muscle function in only a subset of muscles. Additionally, defective muscle stem cells have been implicated in the pathology of some MDs. The biology of muscle stem cells varies depending on the muscles with which they are associated. Here we review the biology of skeletal muscle stem cell populations of eight different muscle groups. Understanding the biological variation of skeletal muscles and their resident stem cells could provide valuable insight into mechanisms underlying the susceptibility of certain muscles to myopathic disease. PMID:26500547

Oak Ridge Graph Analytics for Medical Innovation (ORiGAMI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, Larry W.; Lee, Sangkeun

2016-01-01

In this era of data-driven decisions and discovery where Big Data is producing Bigger Data, data scientists at the Oak Ridge National Laboratory are leveraging unique leadership infrastructure (e.g., Urika XA and Urika GD appliances) to develop scalable algorithms for semantic, logical and statistical reasoning with Big Data (i.e., data stored in databases as well as unstructured data in documents). ORiGAMI is a next-generation knowledge-discovery framework that is: (a) knowledge nurturing (i.e., evolves seamlessly with newer knowledge and data), (b) smart and curious (i.e. using information-foraging and reasoning algorithms to digest content) and (c) synergistic (i.e., interfaces computers with whatmore » they do best to help subject-matter-experts do their best. ORiGAMI has been demonstrated using the National Library of Medicine's SEMANTIC MEDLINE (archive of medical knowledge since 1994).« less

The CIDA Variability Survey of Orion OB1. I. The Low-Mass Population of Ori OB1a and 1b

NASA Astrophysics Data System (ADS)

Briceño, Cesar; Calvet, Nuria; Hernández, J.; Vivas, A. K.; Hartmann, Lee; Downes, J. J.; Berlind, Perry

2005-02-01

We present results of a large-scale, multiepoch optical survey of the Orion OB1 association, carried out with the QUEST camera at the Venezuela National Astronomical Observatory. We identify for the first time the widely spread low-mass, young population in the Ori OB1a and OB1b subassociations. Candidate members were picked up by their variability in the V band and position in color-magnitude diagrams. We obtained spectra to confirm membership. In a region spanning ~68 deg2, we found 197 new young stars; of these, 56 are located in the Ori OB1a subassociation and 141 in Ori OB1b. The spatial distribution of the low-mass young stars is spatially coincident with that of the high-mass members but suggests a much sharper edge to the association. Comparison with the spatial extent of molecular gas and extinction maps indicates that the subassociation Ori OB1b is concentrated within a ringlike structure of radius ~2°(~15 pc at 440 pc), centered roughly on the star ɛ Ori in the Orion belt. The ring is apparent in 13CO and corresponds to a region with an extinction AV>=1. The stars exhibiting strong Hα emission, an indicator of active accretion, are found along this ring, whereas the center is populated with weak Hα-emitting stars. In contrast, Ori OB1a is located in a region devoid of gas and dust. We identify a grouping of stars within a ~3 deg2 area located in Ori OB1a, roughly clustered around the B2 star 25 Ori. The Herbig Ae/Be star V346 Ori is also associated with this grouping, which could be an older analog of σ Ori. Using several sets of evolutionary tracks, we find an age of 7-10 Myr for Ori OB1a and of ~4-6 Myr for Ori OB1b, consistent with previous estimates from OB stars. Indicators such as the equivalent width of Hα and near-IR excesses show that the number of accreting low-mass stars decreases sharply between Ori OB1b and Ori OB1a. These results indicate that although a substantial fraction of accreting disks remain at ages ~5 Myr, inner disks are

An indigenous approach to explore health-related experiences among Māori parents: the Pukapuka Hauora asthma study

PubMed Central

2013-01-01

Background The prevalence of asthma for Indigenous New Zealand Māori is amongst the highest in the world. Recent evidence shows ethnic differences in asthma symptom prevalence in New Zealand have widened, with asthma symptoms and hospitalisation rates consistently higher for Māori across all age-groups, especially children and adolescents. This paper: outlines our qualitative, longitudinal research exploring the practical issues Māori children and their families face trying to achieve optimum asthma outcomes; details the research methods used within this study; and discusses the process evaluation findings of the features that made this approach successful in engaging and retaining participants in the study. Methods Thirty-two Māori families were recruited using a Kaupapa Māori (Māori way) Research approach. Each participated in a series of four in-depth interviews that were carried out at seasonal intervals over the course of one year. Families also took part in an interviewer-administered questionnaire and participated in a Photovoice exercise. All interviews were digitally recorded, transcribed verbatim and independently coded by two researchers. The research team then conducted the analysis and theme development. The questionnaires were analysed separately, with explanations for findings explored within the qualitative data. Results The methodology produced a 100 percent retention rate of the participating families over the course of the follow-up. This was attributed to the research collaboration, the respectful research relationships established with families, and the families’ judgement that the methods used enabled them to tell their stories. The acceptability of the methodology will add to the validity and trustworthiness of the findings. Conclusion Given the extent and persistence of ethnic disparities in childhood asthma management, it is imperative that an indigenous approach be taken to understanding the core issues facing Māori families. By

Uncrossed cortico-muscular projections in humans are abundant to facial muscles of the upper and lower face, but may differ between sexes.

PubMed

Fischer, Urs; Hess, Christian W; Rösler, Kai M

2005-01-01

It is a popular concept in clinical neurology that muscles of the lower face receive predominantly crossed cortico-bulbar motor input, whereas muscles of the upper face receive additional ipsilateral, uncrossed input. To test this notion, we used focal transcranial magnetic brain stimulation to quantify crossed and uncrossed cortico-muscular projections to 6 different facial muscles (right and left Mm. frontalis, nasalis, and orbicularis oris) in 36 healthy right-handed volunteers (15 men, 21 women, mean age 25 years). Uncrossed input was present in 78% to 92% of the 6 examined muscles. The mean uncrossed: crossed response amplitude ratios were 0.74/0.65 in right/left frontalis, 0.73/0.59 in nasalis, and 0.54/0.71 in orbicularis oris; ANOVA p>0.05). Judged by the sizes of motor evoked potentials, the cortical representation of the 3 muscles was similar. The amount of uncrossed projections was different between men and women, since men had stronger left-to-left projections and women stronger right-to-right projections. We conclude that the amount of uncrossed pyramidal projections is not different for muscles of the upper from those of the lower face. The clinical observation that frontal muscles are often spared in central facial palsies must, therefore, be explained differently. Moreover, gender specific lateralization phenomena may not only be present for higher level behavioural functions, but may also affect simple systems on a lower level of motor hierarchy.

DNA recombination-initiation plays a role in the extremely biased inheritance of yeast [rho-] mitochondrial DNA that contains the replication origin ori5.

PubMed

Ling, Feng; Hori, Akiko; Shibata, Takehiko

2007-02-01

Hypersuppressiveness, as observed in Saccharomyces cerevisiae, is an extremely biased inheritance of a small mitochondrial DNA (mtDNA) fragment that contains a replication origin (HS [rho(-)] mtDNA). Our previous studies showed that concatemers (linear head-to-tail multimers) are obligatory intermediates for mtDNA partitioning and are primarily formed by rolling-circle replication mediated by Mhr1, a protein required for homologous mtDNA recombination. In this study, we found that Mhr1 is required for the hypersuppressiveness of HS [ori5] [rho(-)] mtDNA harboring ori5, one of the replication origins of normal ([rho(+)]) mtDNA. In addition, we detected an Ntg1-stimulated double-strand break at the ori5 locus. Purified Ntg1, a base excision repair enzyme, introduced a double-stranded break by itself into HS [ori5] [rho(-)] mtDNA at ori5 isolated from yeast cells. Both hypersuppressiveness and concatemer formation of HS [ori5] [rho(-)] mtDNA are simultaneously suppressed by the ntg1 null mutation. These results support a model in which, like homologous recombination, rolling-circle HS [ori5] [rho(-)] mtDNA replication is initiated by double-stranded breakage in ori5, followed by Mhr1-mediated homologous pairing of the processed nascent DNA ends with circular mtDNA. The hypersuppressiveness of HS [ori5] [rho(-)] mtDNA depends on a replication advantage furnished by the higher density of ori5 sequences and on a segregation advantage furnished by the higher genome copy number on transmitted concatemers.

Magnetic resonance imaging study of eye congenital birth defects in mouse model

PubMed Central

Tucker, Zachary; Mongan, Maureen; Meng, Qinghang; Xia, Ying

2017-01-01

Purpose Embryonic eyelid closure is a well-documented morphogenetic episode in mammalian eye development. Detection of eyelid closure defect in humans is a major challenge because eyelid closure and reopen occur entirely in utero. As a consequence, congenital eye defects that are associated with failure of embryonic eyelid closure remain unknown. To fill the gap, we developed a mouse model of defective eyelid closure. This preliminary work demonstrates that the magnetic resonance imaging (MRI) approach can be used for the detection of extraocular muscle abnormalities in the mouse model. Methods Mice with either normal (Map3k1+/−) or defective (Map3k1−/−) embryonic eyelid closure were used in this study. Images of the extraocular muscles were obtained with a 9.4 T high resolution microimaging MRI system. The extraocular muscles were identified, segmented, and measured in each imaging slice using an in-house program. Results In agreement with histological findings, the imaging data show that mice with defective embryonic eyelid closure develop less extraocular muscle than normal mice. In addition, the size of the eyeballs was noticeably reduced in mice with defective embryonic eyelid closure. Conclusions We demonstrated that MRI can potentially be used for the study of extraocular muscle in the mouse model of the eye open-at-birth defect, despite the lack of specificity of muscle group provided by the current imaging resolution. PMID:28848319

42 CFR 93.318 - Notifying ORI of special circumstances.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Notifying ORI of special circumstances. 93.318 Section 93.318 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE...

42 CFR 93.318 - Notifying ORI of special circumstances.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Notifying ORI of special circumstances. 93.318 Section 93.318 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE...

42 CFR 93.318 - Notifying ORI of special circumstances.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Notifying ORI of special circumstances. 93.318 Section 93.318 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE...

42 CFR 93.318 - Notifying ORI of special circumstances.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Notifying ORI of special circumstances. 93.318 Section 93.318 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE...

42 CFR 93.318 - Notifying ORI of special circumstances.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Notifying ORI of special circumstances. 93.318 Section 93.318 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE...

Provider, father, and bro--Sedentary Māori men and their thoughts on physical activity.

PubMed

Warbrick, Isaac; Wilson, Denise; Boulton, Amohia

2016-02-04

Māori (indigenous peoples of New Zealand) men have a disproportionate prevalence of lifestyle-related illnesses and are targeted for national physical activity initiatives. While physical activity impacts on physical and mental health and overall wellbeing, current approaches to health promotion often lack cultural relevance. Having better understanding and incorporating relevant cultural values and motivators into program designs could improve the success of health initiatives for indigenous and minority men. Nevertheless, little is known about Māori men's preferences, attitudes, or perspectives about physical activity, which are often interpreted through a colonized or dominant Western lens. Understanding perspectives of those groups whose values do not align with dominant cultural approaches will better equip health promoters and trainers to develop relevant community initiatives and private programs for indigenous and minority men. An indigenous research approach informed a qualitative study with 18 sedentary, 'overweight' Māori men aged 28 to 72 years. From 2014 to 2015 these men participated in three focus group discussions aimed at understanding their views about physical activity and exercise. Data were thematically analysed and interpeted using a Māori worldview. Four key themes were identified - Cameraderie and 'Bro-ship'; Adulthood Distractions and Priorities; Problems with Contemporary Gym Culture; and Provider Orientation. Key motivators for physical activity included a sense of 'brotherhood' in sport and physical activity and accountability to others. Participants reported the need to highlight the value of people and relationships, and having an orientation to the collective to enhance physical activity experiences for Māori men in general. Modern lifestyle distractions (such as being time deficient, and family responsibilities) along with other priorities contributed to difficulties incorporating physical activity into their daily lives. In

High variability of facial muscle innervation by facial nerve branches: A prospective electrostimulation study.

PubMed

Raslan, Ashraf; Volk, Gerd Fabian; Möller, Martin; Stark, Vincent; Eckhardt, Nikolas; Guntinas-Lichius, Orlando

2017-06-01

To examine by intraoperative electric stimulation which peripheral facial nerve (FN) branches are functionally connected to which facial muscle functions. Single-center prospective clinical study. Seven patients whose peripheral FN branching was exposed during parotidectomy under FN monitoring received a systematic electrostimulation of each branch starting with 0.1 mA and stepwise increase to 2 mA with a frequency of 3 Hz. The electrostimulation and the facial and neck movements were video recorded simultaneously and evaluated independently by two investigators. A uniform functional allocation of specific peripheral FN branches to a specific mimic movement was not possible. Stimulation of the whole spectrum of branches of the temporofacial division could lead to eye closure (orbicularis oculi muscle function). Stimulation of the spectrum of nerve branches of the cervicofacial division could lead to reactions in the midface (nasal and zygomatic muscles) as well as around the mouth (orbicularis oris and depressor anguli oris muscle function). Frontal and eye region were exclusively supplied by the temporofacial division. The region of the mouth and the neck was exclusively supplied by the cervicofacial division. Nose and zygomatic region were mainly supplied by the temporofacial division, but some patients had also nerve branches of the cervicofacial division functionally supplying the nasal and zygomatic region. FN branches distal to temporofacial and cervicofacial division are not necessarily covered by common facial nerve monitoring. Future bionic devices will need a patient-specific evaluation to stimulate the correct peripheral nerve branches to trigger distinct muscle functions. 4 Laryngoscope, 127:1288-1295, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

42 CFR 93.400 - General statement of ORI authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... POLICIES ON RESEARCH MISCONDUCT Responsibilities of the U.S. Department of Health and Human Services... 42 Public Health 1 2010-10-01 2010-10-01 false General statement of ORI authority. 93.400 Section 93.400 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH...

42 CFR 93.400 - General statement of ORI authority.

Code of Federal Regulations, 2011 CFR

2011-10-01

... POLICIES ON RESEARCH MISCONDUCT Responsibilities of the U.S. Department of Health and Human Services... 42 Public Health 1 2011-10-01 2011-10-01 false General statement of ORI authority. 93.400 Section 93.400 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH...

Genetics and Cell Morphology Analyses of the Actinomyces oris srtA Mutant.

PubMed

Wu, Chenggang; Reardon-Robinson, Melissa Elizabeth; Ton-That, Hung

2016-01-01

Sortase is a cysteine-transpeptidase that anchors LPXTG-containing proteins on the Gram-positive bacterial cell wall. Previously, sortase was considered to be an important factor for bacterial pathogenesis and fitness, but not cell growth. However, the Actinomyces oris sortase is essential for cell viability, due to its coupling to a glycosylation pathway. In this chapter, we describe the methods to generate conditional srtA deletion mutants and identify srtA suppressors by Tn5 transposon mutagenesis. We also provide procedures for analyzing cell morphology of this mutant by thin-section electron microscopy. These techniques can be applied for analyses of other essential genes in A. oris.

Function-sparing tibialis anterior pivoted muscle flap for reconstruction of post-burn and post-traumatic middle-third leg defects with exposed tibia

PubMed Central

Megahed, M.A.

2011-01-01

Summary Reconstruction of the middle third of the leg is a challenging procedure. The tibialis anterior muscle flap can be useful in reconstruction of the middle third of the leg with exposed tibia. The aim of this work was to evaluate the efficacy of tibialis anterior pivoted muscle flap for reconstruction of the middle third of the leg with functional preservation. This study, performed in the Plastic, Reconstructive and Burn Unit, Menoufiya University Hospital, Egypt, included 16 patients (13 males and 3 females) during the period February 2007/May 2010: seven post-burn and nine post-traumatic patients with post-burn middle-third leg defects with exposed tibia. Their ages ranged from 14 to 67 years. A function-sparing lateral split tibialis anterior pivoted muscle flap was used in all the patients. Follow-up ranged from six months to two years. Partial flap loss occurred in one patient (6.25%), there was no post-operative haematoma or infection, and only one case of wound dehiscence (6.25%), managed by secondary suture. No donor site morbidity or any significant functional impairment was observed, and the subjective aesthetic results were satisfactory. Lateral split tibialis anterior pivoted muscle flap is a useful, simple technique, allowing rapid, durable and reliable coverage of middle-third leg defects without significant impairment of function and without sacrificing major nerves or vessels in the foot, and without any donor site morbidity. PMID:22262962

MOST Observations of σ Ori E: Challenging the Centrifugal Breakout Narrative

NASA Astrophysics Data System (ADS)

Townsend, R. H. D.; Rivinius, Th.; Rowe, J. F.; Moffat, A. F. J.; Matthews, J. M.; Bohlender, D.; Neiner, C.; Telting, J. H.; Guenther, D. B.; Kallinger, T.; Kuschnig, R.; Rucinski, S. M.; Sasselov, D.; Weiss, W. W.

2013-05-01

We present results from three weeks' photometric monitoring of the magnetic helium-strong star σ Ori E using the Microvariability and Oscillations of Stars microsatellite. The star's light curve is dominated by twice-per-rotation eclipse-like dimmings arising when magnetospheric clouds transit across and occult the stellar disk. However, no evidence is found for any abrupt centrifugal breakout of plasma from the magnetosphere, either in the residual flux or in the depths of the light minima. Motivated by this finding we compare the observationally inferred magnetospheric mass against that predicted by a breakout analysis. The large discrepancy between the values leads us to argue that centrifugal breakout does not play a significant role in establishing the magnetospheric mass budget of σ Ori E.

Working with racism: a qualitative study of the perspectives of Māori (indigenous peoples of Aotearoa New Zealand) registered nurses on a global phenomenon.

PubMed

Huria, Tania; Cuddy, Jessica; Lacey, Cameron; Pitama, Suzanne

2014-10-01

Substantial health disparities exist between Māori--the indigenous people of Aotearoa New Zealand--and non-Māori New Zealanders. This article explores the experience and impact of racism on Māori registered nurses within the New Zealand health system. The narratives of 15 Māori registered nurses were analyzed to identify the effects of racism. This Māori nursing cohort and the data on racism form a secondary analysis drawn from a larger research project investigating the experiences of indigenous health workers in New Zealand and Canada. Jones's levels of racism were utilized as a coding frame for the structural analysis of the transcribed Māori registered nurse interviews. Participants experienced racism on institutional, interpersonal, and internalized levels, leading to marginalization and being overworked yet undervalued. Māori registered nurses identified a lack of acknowledgement of dual nursing competencies: while their clinical skills were validated, their cultural skills-their skills in Hauora Māori--were often not. Experiences of racism were a commonality. Racism--at every level--can be seen as highly influential in the recruitment, training, retention, and practice of Māori registered nurses. The nursing profession in New Zealand and other countries of indigenous peoples needs to acknowledge the presence of racism within training and clinical environments as well as supporting indigenous registered nurses to develop and implement indigenous dual cultural-clinical competencies. © The Author(s) 2014.

New method for maximum mobilization of temporalis muscle flap.

PubMed

Masic, Tarik; Babajic, Emina; Dervisevic, Almir; Hassouba, Mahmoud

2012-01-01

Pedicled temporalis muscle flap presenting a good flap for closing large craniofacial defects. Careful surgeons usually do not mobilize temporalis muscle flap enough to make appropriate use, fully closure, especially if defect exceeds the median line. Temporalis flap was used in 16 patients, ages ranged between 12 and 76. In all cases defect reconstruction was done by useing new method of extending standard temporal muscle flap. During surgical procedure it is very important to keep periosteal elevator in close contact with the bone. Then, there is no risk for pedicle injury. After vascular pedicle is identified elevating temporal muscle has to be continued by releasing the muscle insertion from the coronoid process. By this way, flap length and arc of rotation is increased. The flap remained viable in all instances. Most of the patients experienced no perioperative complications. There was no major complications or mortality as a result of performed procedures. With this division, flap length was increased at least 2 cm wich is enough for covering defects crossing the midline. Instead of using bilateral temporalis muscle flaps for defect closure, unilateral is sufficient. With this extension of the pedicle length now rotation point is not at the level of the zygomatic arch but lower part mandibular neck.

Unilateral microform cleft lip repair: application of muscle tension line group theory.

PubMed

Yin, Ningbei; Song, Tao; Wu, Jiajun; Chen, Bo; Ma, Hengyuan; Zhao, Zhenmin; Wang, Yongqian; Li, Haidong; Wu, Di

2015-03-01

In microform cleft lip repair, reconstructing the elaborate structures is difficult. We describe a new technique of unilateral microform cleft lip repair that is based on the muscle tension line group theory. According to the shape of Cupid bow, a different small incision is used without creating an obvious cutaneous scar. First, the nasolabial muscle around the nasal floor (the first auxiliary tension line group) is reconstructed, and then the orbicularis oris muscle around the philtrum (the second auxiliary tension line group) is reconstructed based on the muscle tension line group theory. From June 2006 to June 2012, the technique was used in 263 unilateral microform cleft lip repairs. For 18 months, 212 patients were followed up. The appearance of the nasal alar, nasal sill, philtrum, and Cupid bow peak improved. Most patients had a satisfactory appearance. Based on the muscle tension line group theory, using this technique offers the ability to adduct the nasal alar effectively to form a good nasal sill and philtrum.

Redesigning the architecture of policy-making: Engaging with Māori on nanotechnology in New Zealand.

PubMed

Munshi, Debashish; Kurian, Priya A; Morrison, Talei; Morrison, Sandra L

2016-04-01

Although there is an extensive literature on public engagement on the use of new and emerging technologies such as nanotechnology, there is little evidence of the participation of marginalised indigenous communities in processes of such engagement. How do particular cultural values and worldviews shape the perceptions of new technologies among such indigenous peoples? This article addresses this question through an analysis of the deliberations of an indigenous Māori citizens' panel on nanotechnology in Aotearoa New Zealand. An active process of public engagement with the nation's Māori stakeholders, and their conversations with nanotechnology experts, sustainability activists and Māori researchers, helps map an alternative, culture-based architecture of public engagement on policies around new technologies. The analysis is grounded in a concept of active citizenship that we term 'sustainable citizenship'. © The Author(s) 2014.

High nutrition risk related to dietary intake is associated with an increased risk of hospitalisation and mortality for older Māori: LiLACS NZ.

PubMed

North, Sylvia M; Wham, Carol A; Teh, Ruth; Moyes, Simon A; Rolleston, Anna; Kerse, Ngaire

2018-06-11

To investigate the association between domains of nutrition risk with hospitalisations and mortality for New Zealand Māori and non-Māori in advanced age. Within LiLACS NZ, 256 Māori and 399 non-Māori octogenarians were assessed for nutrition risk using the Seniors in the Community: Risk Evaluation for Eating and Nutrition (SCREEN II) questionnaire according to three domains of risk. Sociodemographic and health characteristics were established. Five years from inception, survival analyses examined associations between nutrition risk from the three domains of SCREEN II with all-cause hospital admissions and mortality. For Māori but not non-Māori, lower nutrition risk in the Dietary Intake domain was associated with reduced hospitalisations and mortality (Hazard Ratios [HR] [95%CI] 0.97 [0.95-0.99], p=0.009 and 0.91 [0.86-0.98], p=0.005, respectively). The 'Factors Affecting Intake' domain was associated with mortality (HR, [95%CI] 0.94 [0.89-1.00], p=0.048), adjusted for age, gender, socioeconomic deprivation, education, previous hospital admissions, comorbidities and activities of daily living. Improved dietary adequacy may reduce poor outcomes for older Māori. Implications for public health: Nutrition risk among older Māori is identifiable and treatable. Effort is needed to engage relevant community and whānau (family) support to ensure older Māori have food security and cultural food practices are met. © 2018 The Authors.

The Promotion of a Functional Fibrosis in Skeletal Muscle with Volumetric Muscle Loss Injury Following the Transplantation of Muscle-ECM

DTIC Science & Technology

2013-02-04

i.e., volumetric muscle loss; VML). The explicit goal is to restore functional capacity to the injured tissue by promoting generation of muscle fibers ...3,23,25,27,28]. As a result, trans- plantation of a variety of ECMs in preclinical animal models has resulted in modest levels of muscle fiber generation at...the site of the defect during the initial months post-injury [20,28e30]. However, an apparent enhanced rate of muscle fiber generation at

ORNL’s ORiGAMI Uses Big Data to Help Solve Age-Old Medical Mysteries in Seconds

ScienceCinema

Sukumar, Rangan

2018-01-16

ORiGAMI is a tool for discovering and evaluating potentially interesting associations and creating novel hypothesis in medicine. ORiGAMI will help you “connect the dots” across 70 million knowledge nuggets published in 23 million papers in the medical literature.

MOST OBSERVATIONS OF {sigma} Ori E: CHALLENGING THE CENTRIFUGAL BREAKOUT NARRATIVE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Townsend, R. H. D.; Rivinius, Th.; Rowe, J. F.

2013-05-20

We present results from three weeks' photometric monitoring of the magnetic helium-strong star {sigma} Ori E using the Microvariability and Oscillations of Stars microsatellite. The star's light curve is dominated by twice-per-rotation eclipse-like dimmings arising when magnetospheric clouds transit across and occult the stellar disk. However, no evidence is found for any abrupt centrifugal breakout of plasma from the magnetosphere, either in the residual flux or in the depths of the light minima. Motivated by this finding we compare the observationally inferred magnetospheric mass against that predicted by a breakout analysis. The large discrepancy between the values leads us tomore » argue that centrifugal breakout does not play a significant role in establishing the magnetospheric mass budget of {sigma} Ori E.« less

Autologous Minced Muscle Grafts: A Tissue Engineering Therapy for the Volumetric Loss of Skeletal Muscle

DTIC Science & Technology

2013-07-24

report that over the first 16 wk postinjury, MG transplantation 1) promotes remarkable regeneration of innervated muscle fibers within the defect area...i.e., de novo muscle fiber regeneration); 2) reduced evidence of chronic injury in the remaining muscle mass compared with nonrepaired muscles ...cated nuclei in 30% of fibers observed in nonrepaired muscles ); and 3) significantly improves net torque production (i.e., 55% of the functional deficit

Understanding the role of culture in pain: Māori practitioner perspectives relating to the experience of pain.

PubMed

Magnusson, Jane E; Fennell, Joyce A

2011-01-21

As there is growing interest in the role of cultural diversity within healthcare settings it is important to determine how culture can influence such things as pain. A person's culture can impact not only how they perceive and experience pain but also how they interact with healthcare professionals and adhere to advice provided. To better assess and treat pain in different cultures the perspectives and experiences of that culture must be taken into consideration and therefore the present study was undertaken to better understand Māori perspectives of pain. Māori healthcare providers and kaumātua (tribal leaders/elders) were interviewed in order to gain insight into how pain was perceived and expressed by Māori with whom they had health-related interactions. The interviews reflected themes consistent within the greater body of literature in that as with many cultures, Māori perceive pain as a multidimensional experience impacting them physically, psychologically, socially and spiritually. While our findings indicate that there is a commonality between cultures with regard to the experience of pain, it is valuable to understand a culture's perceptions and experiences regarding pain before assessing and treating it as indicated in the findings from this study wherein cultural factors such as the role of the whānau (family) and the importance of the development of relationships with healthcare providers were points of emphasis in terms of ways to enhance Māori health.

Evidence for recombination between a sialidase (nanH) of Actinomyces naeslundii and Actinomyces oris, previously named ‘Actinomyces naeslundii genospecies 1 and 2’

PubMed Central

Do, Thuy; Henssge, Uta; Gilbert, Steven C; Clark, Douglas; Beighton, David

2008-01-01

Actinomyces spp., predominant members of human oral biofilms, may use extracellular sialidase to promote adhesion, deglycosylate immunoglobulins and liberation of nutrients. Partial nanH gene sequences (1077 bp) from Actinomyces oris (n =74), Actinomyces naeslundii (n =30), Actinomyces viscosus (n =1) and Actinomyces johnsonii (n =2) which included the active-site region and the bacterial neuraminidase repeats (BNRs) were compared. The sequences were aligned and each species formed a distinct cluster with five isolates having intermediate positions. These five isolates (two A. oris and three A. naeslundii) exhibited interspecies recombination. The nonsynonymous/synonymous ratio was <1 for both A. oris and A. naeslundii indicating that nanH in both species is under stabilizing selective pressure; nonsynonymous mutations are not selected. However, for A. oris significant negative values in tests for neutral selection suggested the rate of mutation in A. oris was greater than in A. naeslundii but with selection against nonsynonymous mutations. This was supported by the observation that the frequency of polymorphic sites in A. oris, which were monomorphic in A. naeslundii was significantly greater than the frequency of polymorphic sites in A. naeslundii which were monomorphic in A. oris (χ2=7.011; P =0.00081). The higher proportions of A. oris in the oral biofilm might be explained by the higher mutation rate facilitating an increased ability to respond successfully to environmental stress. PMID:18823396

A Type I Signal Peptidase Is Required for Pilus Assembly in the Gram-Positive, Biofilm-Forming Bacterium Actinomyces oris

PubMed Central

Siegel, Sara D.

2016-01-01

ABSTRACT The Gram-positive bacterium Actinomyces oris, a key colonizer in the development of oral biofilms, contains 18 LPXTG motif-containing proteins, including fimbrillins that constitute two fimbrial types critical for adherence, biofilm formation, and polymicrobial interactions. Export of these protein precursors, which harbor a signal peptide, is thought to be mediated by the Sec machine and require cleavage of the signal peptide by type I signal peptidases (SPases). Like many Gram-positive bacteria, A. oris expresses two SPases, named LepB1 and LepB2. The latter has been linked to suppression of lethal “glyco-stress,” caused by membrane accumulation of the LPXTG motif-containing glycoprotein GspA when the housekeeping sortase srtA is genetically disrupted. Consistent with this finding, we show here that a mutant lacking lepB2 and srtA was unable to produce high levels of glycosylated GspA and hence was viable. However, deletion of neither lepB1 nor lepB2 abrogated the signal peptide cleavage and glycosylation of GspA, indicating redundancy of SPases for GspA. In contrast, the lepB2 deletion mutant failed to assemble the wild-type levels of type 1 and 2 fimbriae, which are built by the shaft fimbrillins FimP and FimA, respectively; this phenotype was attributed to aberrant cleavage of the fimbrillin signal peptides. Furthermore, the lepB2 mutants, including the catalytically inactive S101A and K169A variants, exhibited significant defects in polymicrobial interactions and biofilm formation. Conversely, lepB1 was dispensable for the aforementioned processes. These results support the idea that LepB2 is specifically utilized for processing of fimbrial proteins, thus providing an experimental model with which to study the basis of type I SPase specificity. IMPORTANCE Sec-mediated translocation of bacterial protein precursors across the cytoplasmic membrane involves cleavage of their signal peptide by a signal peptidase (SPase). Like many Gram

A Type I Signal Peptidase Is Required for Pilus Assembly in the Gram-Positive, Biofilm-Forming Bacterium Actinomyces oris.

PubMed

Siegel, Sara D; Wu, Chenggang; Ton-That, Hung

2016-08-01

The Gram-positive bacterium Actinomyces oris, a key colonizer in the development of oral biofilms, contains 18 LPXTG motif-containing proteins, including fimbrillins that constitute two fimbrial types critical for adherence, biofilm formation, and polymicrobial interactions. Export of these protein precursors, which harbor a signal peptide, is thought to be mediated by the Sec machine and require cleavage of the signal peptide by type I signal peptidases (SPases). Like many Gram-positive bacteria, A. oris expresses two SPases, named LepB1 and LepB2. The latter has been linked to suppression of lethal "glyco-stress," caused by membrane accumulation of the LPXTG motif-containing glycoprotein GspA when the housekeeping sortase srtA is genetically disrupted. Consistent with this finding, we show here that a mutant lacking lepB2 and srtA was unable to produce high levels of glycosylated GspA and hence was viable. However, deletion of neither lepB1 nor lepB2 abrogated the signal peptide cleavage and glycosylation of GspA, indicating redundancy of SPases for GspA. In contrast, the lepB2 deletion mutant failed to assemble the wild-type levels of type 1 and 2 fimbriae, which are built by the shaft fimbrillins FimP and FimA, respectively; this phenotype was attributed to aberrant cleavage of the fimbrillin signal peptides. Furthermore, the lepB2 mutants, including the catalytically inactive S101A and K169A variants, exhibited significant defects in polymicrobial interactions and biofilm formation. Conversely, lepB1 was dispensable for the aforementioned processes. These results support the idea that LepB2 is specifically utilized for processing of fimbrial proteins, thus providing an experimental model with which to study the basis of type I SPase specificity. Sec-mediated translocation of bacterial protein precursors across the cytoplasmic membrane involves cleavage of their signal peptide by a signal peptidase (SPase). Like many Gram-positive bacteria, A. oris expresses

Confidence and connectedness: Indigenous Māori women's views on personal safety in the context of intimate partner violence.

PubMed

Wilson, Denise; Jackson, Debra; Herd, Ruth

2016-07-01

Māori (New Zealand) women, similar to women belonging to Indigenous and minority groups globally, have high levels of lifetime abuse, assault, and homicide, and are over-represented in events that compromise their safety. We sought insights into how Māori women view safety. Twenty Māori women's narratives revealed safety as a holistic concept involving a number of different elements. We found women had developed an acute sense of the concept of safety. They had firm views and clear strategies to maintain their own safety and that of their female family and friends. These women also provided insights into their experiences of feeling unsafe.

Changes to smoking habits and addiction following tobacco excise tax increases: a comparison of Māori, Pacific and New Zealand European smokers.

PubMed

Tucker, Megan R; Kivell, Bronwyn M; Laugesen, Murray; Grace, Randolph C

2017-02-01

To compare changes in smoking habit and psychological addiction in Māori/Pacific and NZ European smokers in response to two annual excise tax increases from 2012 to 2014. Smokers from New Zealand cities completed questionnaires at three time points before and after two excise tax increases. There were no significant differences in cigarettes per day or psychological addiction at baseline, but a linear decline in both measures was observed in Māori/Pacific and NZ European smokers. Cigarettes per day reduced at a greater rate for Māori/Pacific than NZ European smokers but dependence did not. Results indicated that Māori/Pacific smokers' demand for cigarettes may be more price sensitive than NZ European smokers. Implications for Public Health: Tobacco excise tax may be particularly effective for Māori/Pacific smokers and may contribute to reductions in smoking-related health inequalities in NZ. © 2016 The Authors.

42 CFR 93.217 - Office of Research Integrity or ORI.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Office of Research Integrity or ORI. 93.217 Section 93.217 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE...

Muscle-Specific Vascular Endothelial Growth Factor Deletion Induces Muscle Capillary Rarefaction Creating Muscle Insulin Resistance

PubMed Central

Bonner, Jeffrey S.; Lantier, Louise; Hasenour, Clinton M.; James, Freyja D.; Bracy, Deanna P.; Wasserman, David H.

2013-01-01

Muscle insulin resistance is associated with a reduction in vascular endothelial growth factor (VEGF) action and muscle capillary density. We tested the hypothesis that muscle capillary rarefaction critically contributes to the etiology of muscle insulin resistance in chow-fed mice with skeletal and cardiac muscle VEGF deletion (mVEGF−/−) and wild-type littermates (mVEGF+/+) on a C57BL/6 background. The mVEGF−/− mice had an ∼60% and ∼50% decrease in capillaries in skeletal and cardiac muscle, respectively. The mVEGF−/− mice had augmented fasting glucose turnover. Insulin-stimulated whole-body glucose disappearance was blunted in mVEGF−/− mice. The reduced peripheral glucose utilization during insulin stimulation was due to diminished in vivo cardiac and skeletal muscle insulin action and signaling. The decreased insulin-stimulated muscle glucose uptake was independent of defects in insulin action at the myocyte, suggesting that the impairment in insulin-stimulated muscle glucose uptake was due to poor muscle perfusion. The deletion of VEGF in cardiac muscle did not affect cardiac output. These studies emphasize the importance for novel therapeutic approaches that target the vasculature in the treatment of insulin-resistant muscle. PMID:23002035

Bridging extra large defects of peripheral nerves: possibilities and limitations of alternative biological grafts from acellular muscle and Schwann cells.

PubMed

Keilhoff, Gerburg; Prätsch, Florian; Wolf, Gerald; Fansa, Hisham

2005-01-01

Defects of peripheral nerves are bridged with autologous nerve grafts. Tissue-engineered nerve grafts offer a laboratory-based alternative to overcome limited donor nerve availability. Our objective was to evaluate whether a graft made from acellular muscle enriched with cultivated Schwann cells can bridge extra large gaps where conventional conduits usually fail. Our well-established rat sciatic nerve model was used with an increased gap length of 50 mm. The conduits consisted of freeze-thawed or chemically extracted homologous acellular rat rectus muscles and implanted Schwann cells. Autologous nerve grafts were used for control purposes. Biocompatibility of the grafts was demonstrated by Schwann cell settlement, revascularization, and macrophage recruitment. After 12 weeks regeneration was assessed clinically, histologically, and morphometrically. The control group showed superior results regarding axon counts, histologic appearance, and functional recovery compared with the muscle grafts. The chemically extracted conduits completely failed to support nerve regeneration. They were not stable enough to bridge longer nerve gaps with an expanded regeneration time. On the basis of morphological parameters freeze-thawed muscle grafts were, however, able to support peripheral nerve regeneration even over the extralong distance of 50 mm, and therefore are of potential benefit for new therapeutic strategies.

"I Want to Walk with My Moko." The Application of Social Cognitive Theory in the Creation of a Diabetes Prevention Documentary with New Zealand Māori.

PubMed

Farmer, Alison; Edgar, Timothy; Gage, Jeffrey; Kirk, Ray

2018-01-01

Type 2 diabetes is almost three times more prevalent in the indigenous people of New Zealand (Māori) than non-Māori. Despite the high rate of diabetes there is a low level of diabetes knowledge and awareness in the Māori community. Several studies of Māori health identify a need for new health communication approaches to diabetes prevention in order to reduce the gap between Māori and non-Māori disease rates. We applied a Community-Based Participatory Research (CBPR) framework and behavioral theory to create a culturally appropriate documentary for Māori at risk for type 2 diabetes. We discuss how we utilized Bandura's social cognitive theory to provide a culturally sensitive theoretical basis for behavior change messaging. We outline why social cognitive theory was a culturally appropriate foundation and describe the role of the community in shaping the documentary messaging. A culture-centered approach utilizing participatory methodologies and culturally sensitive behavioral change theory might serve as a model for creating health communication resources in collaboration with other indigenous communities.

Engineering functional and histological regeneration of vascularized skeletal muscle.

PubMed

Gilbert-Honick, Jordana; Iyer, Shama R; Somers, Sarah M; Lovering, Richard M; Wagner, Kathryn; Mao, Hai-Quan; Grayson, Warren L

2018-05-01

Tissue engineering strategies to treat patients with volumetric muscle loss (VML) aim to recover the structure and contractile function of lost muscle tissue. Here, we assessed the capacity of novel electrospun fibrin hydrogel scaffolds seeded with murine myoblasts to regenerate the structure and function of damaged muscle within VML defects to the mouse tibialis anterior muscle. The electrospun fibrin scaffolds provide pro-myogenic alignment and stiffness cues, myomimetic hierarchical structure, suturability, and scale-up capabilities. Myoblast-seeded scaffolds enabled remarkable muscle regeneration with high myofiber and vascular densities after 2 and 4 weeks, mimicking that of native skeletal muscle, while acellular scaffolds lacked muscle regeneration. Both myoblast-seeded and acellular scaffolds fully recovered muscle contractile function to uninjured values after 2 and 4 weeks. Electrospun scaffolds pre-vascularized with co-cultured human endothelial cells and human adipose-derived stem cells implanted into VML defects for 2 weeks anastomosed with host vasculature and were perfused with host red blood cells. These data demonstrate the significant potential of electrospun fibrin scaffolds seeded with myoblasts to fully regenerate the structure and function of volumetric muscle defects and these scaffolds offer a promising treatment option for patients with VML. Copyright © 2018 Elsevier Ltd. All rights reserved.

Role for a region of helically unstable DNA within the Epstein-Barr virus latent cycle origin of DNA replication oriP in origin function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polonskaya, Zhanna; Benham, Craig J.; Hearing, Janet

The minimal replicator of the Epstein-Barr virus (EBV) latent cycle origin of DNA replication oriP is composed of two binding sites for the Epstein-Barr virus nuclear antigen-1 (EBNA-1) and flanking inverted repeats that bind the telomere repeat binding factor TRF2. Although not required for minimal replicator activity, additional binding sites for EBNA-1 and TRF2 and one or more auxiliary elements located to the right of the EBNA-1/TRF2 sites are required for the efficient replication of oriP plasmids. Another region of oriP that is predicted to be destabilized by DNA supercoiling is shown here to be an important functional component ofmore » oriP. The ability of DNA fragments of unrelated sequence and possessing supercoiled-induced DNA duplex destabilized (SIDD) structures, but not fragments characterized by helically stable DNA, to substitute for this component of oriP demonstrates a role for the SIDD region in the initiation of oriP-plasmid DNA replication.« less

The proximally based long peroneal muscle turnover flap: A novel salvage flap for small to medium-sized defects of the knee.

PubMed

Wagner, Till; Hupkens, Pieter; Slater, Nicholas J; Ulrich, Dietmar J O

2016-04-01

Coverage of soft-tissue defects of the knee due to multiple operations, trauma, and infection remains a surgical challenge. Often, these defects are repaired using free tissue transfer. The aim of this study was to find an easy and reliable local method of repair for small to medium-sized defects. The authors describe a new surgical option for tissue coverage using a proximally based long peroneal muscle turnover flap (LPTF) with split-thickness skin graft. Proximally based LPTFs were harvested and transposed into same-size created defects in five cadavers. After optimizing this technique, it was clinically used in two patients with defects secondary to total knee replacement revisions. Average cadaver flap size was 4.7 × 15.8 cm allowing reach of all knee joint areas and was based consistently on a sufficient (2-mm-diameter average) proximal arterial branch of the anterior tibial artery. Donor sites were closed without tension. Subsequent application of the flap on two patients resulted in good functional outcome. The proximally based LPTF is a new option available in the reconstruction of knee defects and should be added to the reconstructive surgeon's armamentarium of pedicled flaps, providing short operating time and promising clinical outcome. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Reconstruction of a large calvarial traumatic defect using a custom-made porous hydroxyapatite implant covered by a free latissimus dorsi muscle flap in an 11-year-old patient.

PubMed

Morice, Anne; Kolb, Frédéric; Picard, Arnaud; Kadlub, Natacha; Puget, Stéphanie

2017-01-01

Reconstruction of complex skull defects requires collaboration between neurosurgeons and plastic surgeons to choose the most appropriate procedure, especially in growing children. The authors describe herein the reconstruction of an extensive traumatic bone and soft tissue defect of the cranial vault in an 11-year-old boy. The size of the defect, quality of the tissues, and patient's initial condition required a 2-stage approach. Ten months after an initial emergency procedure in which lacerated bone and soft tissue were excised, reconstruction was performed. The bone defect, situated on the left frontoparietal region, was 85 cm 2 and was filled by a custom-made porous hydroxyapatite implant. The quality of the overlying soft tissue did not allow the use of classic local and locoregional coverage techniques. A free latissimus dorsi muscle flap branched on the contralateral superficial temporal pedicle was used and left for secondary healing to take advantage of scar retraction and to minimize alopecia. Stable well-vascularized implant coverage as well as an esthetically pleasing skull shape was achieved. Results in this case suggest that concomitant reconstruction of large calvarial defects by cranioplasty with a custom-made hydroxyapatite implant covered by a free latissimus dorsi muscle flap is a safe and efficient procedure in children, provided that there is no underlying infection of the operative site.

42 CFR 93.217 - Office of Research Integrity or ORI.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Office of Research Integrity or ORI. 93.217 Section 93.217 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC HEALTH SERVICE POLICIES ON RESEARCH MISCONDUCT Definitions §...

Intramuscular variation in fresh ham muscle color

USDA-ARS?s Scientific Manuscript database

This experiment was conducted to characterize a defect involving pale muscle tissue in the superficial, ventral portion of ham muscles, resulting in two-toned appearance of cured ham products. Biceps femoris muscles (n = 200), representing 3 production systems, were obtained from the ham-boning lin...

Application of MLST and Pilus Gene Sequence Comparisons to Investigate the Population Structures of Actinomyces naeslundii and Actinomyces oris

PubMed Central

Henssge, Uta; Do, Thuy; Gilbert, Steven C.; Cox, Steven; Clark, Douglas; Wickström, Claes; Ligtenberg, A. J. M.; Radford, David R.; Beighton, David

2011-01-01

Actinomyces naeslundii and Actinomyces oris are members of the oral biofilm. Their identification using 16S rRNA sequencing is problematic and better achieved by comparison of metG partial sequences. A. oris is more abundant and more frequently isolated than A. naeslundii. We used a multi-locus sequence typing approach to investigate the genotypic diversity of these species and assigned A. naeslundii (n = 37) and A. oris (n = 68) isolates to 32 and 68 sequence types (ST), respectively. Neighbor-joining and ClonalFrame dendrograms derived from the concatenated partial sequences of 7 house-keeping genes identified at least 4 significant subclusters within A. oris and 3 within A. naeslundii. The strain collection we had investigated was an under-representation of the total population since at least 3 STs composed of single strains may represent discrete clusters of strains not well represented in the collection. The integrity of these sub-clusters was supported by the sequence analysis of fimP and fimA, genes coding for the type 1 and 2 fimbriae, respectively. An A. naeslundii subcluster was identified with both fimA and fimP genes and these strains were able to bind to MUC7 and statherin while all other A. naeslundii strains possessed only fimA and did not bind to statherin. An A. oris subcluster harboured a fimA gene similar to that of Actinomyces odontolyticus but no detectable fimP failed to bind significantly to either MUC7 or statherin. These data are evidence of extensive genotypic and phenotypic diversity within the species A. oris and A. naeslundii but the status of the subclusters identified here will require genome comparisons before their phylogenic position can be unequivocally established. PMID:21738661

Application of MLST and pilus gene sequence comparisons to investigate the population structures of Actinomyces naeslundii and Actinomyces oris.

PubMed

Henssge, Uta; Do, Thuy; Gilbert, Steven C; Cox, Steven; Clark, Douglas; Wickström, Claes; Ligtenberg, A J M; Radford, David R; Beighton, David

2011-01-01

Actinomyces naeslundii and Actinomyces oris are members of the oral biofilm. Their identification using 16S rRNA sequencing is problematic and better achieved by comparison of metG partial sequences. A. oris is more abundant and more frequently isolated than A. naeslundii. We used a multi-locus sequence typing approach to investigate the genotypic diversity of these species and assigned A. naeslundii (n = 37) and A. oris (n = 68) isolates to 32 and 68 sequence types (ST), respectively. Neighbor-joining and ClonalFrame dendrograms derived from the concatenated partial sequences of 7 house-keeping genes identified at least 4 significant subclusters within A. oris and 3 within A. naeslundii. The strain collection we had investigated was an under-representation of the total population since at least 3 STs composed of single strains may represent discrete clusters of strains not well represented in the collection. The integrity of these sub-clusters was supported by the sequence analysis of fimP and fimA, genes coding for the type 1 and 2 fimbriae, respectively. An A. naeslundii subcluster was identified with both fimA and fimP genes and these strains were able to bind to MUC7 and statherin while all other A. naeslundii strains possessed only fimA and did not bind to statherin. An A. oris subcluster harboured a fimA gene similar to that of Actinomyces odontolyticus but no detectable fimP failed to bind significantly to either MUC7 or statherin. These data are evidence of extensive genotypic and phenotypic diversity within the species A. oris and A. naeslundii but the status of the subclusters identified here will require genome comparisons before their phylogenic position can be unequivocally established.

Āwhina Revolution: A Bayesian Analysis of Undergraduate and Postgraduate Completion Rates from a Program for Māori and Pacific Success in STEM Disciplines.

PubMed

Richardson, Ken; Clark, Zaramasina; Gaines, Michael; Kingi, Hautahi; Miller, Sonja; Pearson, Willie; Richardson, Liz

2018-01-01

Māori and Pacific students generally do not attain the same levels of tertiary success as New Zealanders of European descent, particularly in science, technology, engineering, and mathematics (STEM) subjects. Te Rōpū Āwhina (Āwhina), an equity initiative at Victoria University of Wellington in New Zealand between 1999 and 2015, aimed to produce Māori and Pacific professionals in STEM disciplines who contribute to Māori and Pacific community development and leadership. A hierarchical Bayesian approach was used to estimate posterior standardized completion rates for 3-year undergraduate and 2-year postgraduate degrees undertaken by non-Māori-Pacific and Māori-Pacific students. Results were consistent with an Āwhina effect, that is, Āwhina's positive influence on (combined) Māori and Pacific success. © 2018 K. Richardson et al. CBE—Life Sciences Education © 2018 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI-deficient muscles

PubMed Central

Grumati, Paolo; Coletto, Luisa; Schiavinato, Alvise; Castagnaro, Silvia; Bertaggia, Enrico

2011-01-01

Autophagy is a catabolic process that provides the degradation of altered/damaged organelles through the fusion between autophagosomes and lysosomes. Proper regulation of the autophagic flux is fundamental for the homeostasis of skeletal muscles in physiological conditions and in response to stress. Defective as well as excessive autophagy is detrimental for muscle health and has a pathogenic role in several forms of muscle diseases. Recently, we found that defective activation of the autophagic machinery plays a key role in the pathogenesis of muscular dystrophies linked to collagen VI. Impairment of the autophagic flux in collagen VI null (Col6a1–/–) mice causes accumulation of dysfunctional mitochondria and altered sarcoplasmic reticulum, leading to apoptosis and degeneration of muscle fibers. Here we show that physical exercise activates autophagy in skeletal muscles. Notably, physical training exacerbated the dystrophic phenotype of Col6a1–/– mice, where autophagy flux is compromised. Autophagy was not induced in Col6a1–/– muscles after either acute or prolonged exercise, and this led to a marked increase of muscle wasting and apoptosis. These findings indicate that proper activation of autophagy is important for muscle homeostasis during physical activity. PMID:22024752

Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chatterjee, Somik; Yin, Hongshan; Department of Cardiovascular Medicine, Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, Hebei

Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response ismore » observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1{sup −/−} mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases. - Highlights: • Bmal1 is highly inducible by muscle injury and myogenic stimuli. • Genetic ablation of Bmal1 significantly impairs muscle regeneration. • Bmal1 promotes satellite cell expansion during muscle regeneration. • Bmal1-deficient primary myoblasts display attenuated growth and proliferation.« less

Single-stage Reconstruction of Elbow Flexion Associated with Massive Soft-Tissue Defect Using the Latissimus Dorsi Muscle Bipolar Rotational Transfer

PubMed Central

Cuéllar, Vanessa G.; Ghiassi, Alidad; Sharpe, Frances

2016-01-01

Introduction: In the upper extremity, the latissimus dorsi muscle can be used as an ipsilateral rotational muscle flap for soft-tissue coverage or functional reconstruction of arm and elbow. Patients who have both major soft-tissue loss and functional deficits can be successfully treated with a single-stage functional latissimus dorsi rotational muscle transfer that provides simultaneous soft-tissue coverage and functional reconstruction. Methods: Our data base was queried for all patients undergoing a rotational latissimus dorsi muscle transfer for simultaneous soft-tissue coverage and functional reconstruction of elbow flexion. Four patients were identified. A chart review documented the mechanism of injury, associated injuries, soft-tissue defect size, number of surgical procedures, length of follow-up, last elbow range of motion, and flexion strength. Results: Four patients with loss of elbow flexion due to traumatic loss of the anterior compartment muscles and the overlying soft tissue underwent simultaneous soft-tissue coverage and elbow flexorplasty using the ipsilateral latissimus dorsi as a bipolar muscle rotational tissue transfer. All flaps survived and had a recovery of Medical Research Council Grade 4/5 elbow flexion strength. No additional procedures were required for elbow flexion. The surgical technique is described and supplemented with surgical technique video and patient outcome. Conclusions: This patient series augments the data provided in other series supporting the safety and efficacy of this procedure which provides both soft-tissue coverage and functional restoration of elbow flexion as a single-stage procedure in the setting of massive traumatic soft-tissue loss of the arm. PMID:27757363

Single-stage Reconstruction of Elbow Flexion Associated with Massive Soft-Tissue Defect Using the Latissimus Dorsi Muscle Bipolar Rotational Transfer.

PubMed

Stevanovic, Milan V; Cuéllar, Vanessa G; Ghiassi, Alidad; Sharpe, Frances

2016-09-01

In the upper extremity, the latissimus dorsi muscle can be used as an ipsilateral rotational muscle flap for soft-tissue coverage or functional reconstruction of arm and elbow. Patients who have both major soft-tissue loss and functional deficits can be successfully treated with a single-stage functional latissimus dorsi rotational muscle transfer that provides simultaneous soft-tissue coverage and functional reconstruction. Our data base was queried for all patients undergoing a rotational latissimus dorsi muscle transfer for simultaneous soft-tissue coverage and functional reconstruction of elbow flexion. Four patients were identified. A chart review documented the mechanism of injury, associated injuries, soft-tissue defect size, number of surgical procedures, length of follow-up, last elbow range of motion, and flexion strength. Four patients with loss of elbow flexion due to traumatic loss of the anterior compartment muscles and the overlying soft tissue underwent simultaneous soft-tissue coverage and elbow flexorplasty using the ipsilateral latissimus dorsi as a bipolar muscle rotational tissue transfer. All flaps survived and had a recovery of Medical Research Council Grade 4/5 elbow flexion strength. No additional procedures were required for elbow flexion. The surgical technique is described and supplemented with surgical technique video and patient outcome. This patient series augments the data provided in other series supporting the safety and efficacy of this procedure which provides both soft-tissue coverage and functional restoration of elbow flexion as a single-stage procedure in the setting of massive traumatic soft-tissue loss of the arm.

Fabrication, characterization, and heuristic trade space exploration of magnetically actuated Miura-Ori origami structures

NASA Astrophysics Data System (ADS)

Cowan, Brett; von Lockette, Paris R.

2017-04-01

The authors develop magnetically actuated Miura-Ori structures through observation, experiment, and computation using an initially heuristic strategy followed by trade space visualization and optimization. The work is novel, especially within origami engineering, in that beyond final target shape approximation, Miura-Ori structures in this work are additionally evaluated for the shape approximation while folding and for their efficient use of their embedded actuators. The structures consisted of neodymium magnets placed on the panels of silicone elastomer substrates cast in the Miura-Ori folding pattern. Initially four configurations, arrangements of magnets on the panels, were selected based on heuristic arguments that (1) maximized the amount of magnetic torque applied to the creases and (2) reduced the number of magnets needed to affect all creases in the pattern. The results of experimental and computational performance metrics were used in a weighted sum model to predict the optimum configuration, which was then fabricated and experimentally characterized for comparison to the initial prototypes. As expected, optimization of magnet placement and orientation was effective at increasing the degree of theoretical useful work. Somewhat unexpectedly, however, trade space results showed that even after optimization, the configuration with the most number of magnets was least effective, per magnet, at directing its actuation to the structure’s creases. Overall, though the winning configuration experimentally outperformed its initial, non-optimal counterparts, results showed that the choice of optimum configuration was heavily dependent on the weighting factors. These results highlight both the ability of the Miura-Ori to be actuated with external magnetic stimuli, the effectiveness of a heuristic design approach that focuses on the actuation mechanism, and the need to address path-dependent metrics in assessing performance in origami folding structures.

Cayler cardiofacial syndrome and del 22q11: Part of the CATCH22 phenotype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giannotti, A.; Digilio, M.C.; Marino, B.

1994-11-15

The authors report evidence supporting the hypothesis that del(22)(q11) can be a pathogenetic mechanism for the association between hypoplasia of the depressor anguli oris muscle (DAOM) and conotruncal cardiac malformations. A series of over 180 patients was investigated with deletions of 22q11 with conotruncal defects. About 2/3 of these patients had isolated, nonfamilial cardiac defects. Hemizygosity was searched using the HD7k probe and densitometric analysis. In the patients with molecular evidence of del(22)(q11), hemizygosity was confirmed also using fluorescence in situ hybridization (FISH) with SC11.1 probe. No deletion was found in the parents of hemizygous patients. 16 refs.

Impaired Spermatogenesis, Muscle, and Erythrocyte Function in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.

PubMed

Horiuchi, Keiko; Perez-Cerezales, Serafín; Papasaikas, Panagiotis; Ramos-Ibeas, Priscila; López-Cardona, Angela Patricia; Laguna-Barraza, Ricardo; Fonseca Balvís, Noelia; Pericuesta, Eva; Fernández-González, Raul; Planells, Benjamín; Viera, Alberto; Suja, Jose Angel; Ross, Pablo Juan; Alén, Francisco; Orio, Laura; Rodriguez de Fonseca, Fernando; Pintado, Belén; Valcárcel, Juan; Gutiérrez-Adán, Alfonso

2018-04-03

The U2AF35-like ZRSR1 has been implicated in the recognition of 3' splice site during spliceosome assembly, but ZRSR1 knockout mice do not show abnormal phenotypes. To analyze ZRSR1 function and its precise role in RNA splicing, we generated ZRSR1 mutant mice containing truncating mutations within its RNA-recognition motif. Homozygous mutant mice exhibited severe defects in erythrocytes, muscle stretch, and spermatogenesis, along with germ cell sloughing and apoptosis, ultimately leading to azoospermia and male sterility. Testis RNA sequencing (RNA-seq) analyses revealed increased intron retention of both U2- and U12-type introns, including U12-type intron events in genes with key functions in spermatogenesis and spermatid development. Affected U2 introns were commonly found flanking U12 introns, suggesting functional cross-talk between the two spliceosomes. The splicing and tissue defects observed in mutant mice attributed to ZRSR1 loss of function suggest a physiological role for this factor in U12 intron splicing. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Unit Advancement Flap for Lower Lip Reconstruction.

PubMed

Ogino, Akihiro; Onishi, Kiyoshi; Okada, Emi; Nakamichi, Miho

2018-05-01

Lower lip reconstruction requires consideration of esthetic and functional outcome in selecting a surgical procedure, and reconstruction with local tissue is useful. The authors reconstructed full-thickness defects with a unit advancement flap. Reconstruction was performed using this method in 4 patients with lower lip squamous cell carcinoma in whom tumor resection with preservation of the mouth angle was possible. The lower lip resection width was 30 to 45 mm, accounting for 50% to 68% of the entire width of the lower lip. The flap was prepared by lateral extension from above the mental unit and matched with the potential wrinkle line of the lower lip in order to design a unit morphology surrounded by the anterior margin of the depressor labii inferioris muscle. It was elevated as a full-thickness flap composed of the orbicularis oris muscle, skin, and mucosa of the residual lower lip from the bilateral sides, and advanced to the defect. Flap transfer was adjusted by small triangular resection of the skin on the lateral side of the mental unit. The postoperative scar was inconspicuous in all patients and there was no impairment of the mouth opening-closing or articulation functions. This was a relatively simple surgical procedure. A blood supply of the flap was stable, and continuity of the orbicularis oris muscle was reconstructed by transferred the residual lower lip advancement flap from the bilateral sides. The postoperative mouth opening-closing function was sufficient, and dentures could be placed from an early phase in elderly patients. The postoperative scar was consistent with the lip unit morphology, being esthetically superior. This procedure may be applicable for reconstruction of defects approximately 1/3 to 2/3 the width of the lower lip where the mouth angle is preserved.

Cosmetic reconstruction of temporal defect following pterional [corrected] craniotomy.

PubMed

Badie, B

1996-04-01

Depression of the temporal fossa that is often caused by atrophy of the temporalis muscle or superficial temporal fat pad may be an unavoidable defect following pterional craniotomy. Various techniques have been previously described to correct this disfiguring defect. Most techniques, however, require drilling holes into the cranium or the synthetic grafts for attachment of the temporalis muscle. A simple method is described by which a temporal fossa depression is repaired with methylmethacrylate bone cement and a new superior temporal line is created for attachment of the temporalis muscle without the need to drill suture holes into the acrylic or the cranium. The technique described has been used on several patients with excellent cosmetic outcome.

Neuromuscular imaging in inherited muscle diseases

PubMed Central

Kley, Rudolf A.; Fischer, Dirk

2010-01-01

Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies. PMID:20422195

Din7 and Mhr1 expression levels regulate double-strand-break–induced replication and recombination of mtDNA at ori5 in yeast

PubMed Central

Ling, Feng; Hori, Akiko; Yoshitani, Ayako; Niu, Rong; Yoshida, Minoru; Shibata, Takehiko

2013-01-01

The Ntg1 and Mhr1 proteins initiate rolling-circle mitochondrial (mt) DNA replication to achieve homoplasmy, and they also induce homologous recombination to maintain mitochondrial genome integrity. Although replication and recombination profoundly influence mitochondrial inheritance, the regulatory mechanisms that determine the choice between these pathways remain unknown. In Saccharomyces cerevisiae, double-strand breaks (DSBs) introduced by Ntg1 at the mitochondrial replication origin ori5 induce homologous DNA pairing by Mhr1, and reactive oxygen species (ROS) enhance production of DSBs. Here, we show that a mitochondrial nuclease encoded by the nuclear gene DIN7 (DNA damage inducible gene) has 5′-exodeoxyribonuclease activity. Using a small ρ− mtDNA bearing ori5 (hypersuppressive; HS) as a model mtDNA, we revealed that DIN7 is required for ROS-enhanced mtDNA replication and recombination that are both induced at ori5. Din7 overproduction enhanced Mhr1-dependent mtDNA replication and increased the number of residual DSBs at ori5 in HS-ρ− cells and increased deletion mutagenesis at the ori5 region in ρ+ cells. However, simultaneous overproduction of Mhr1 suppressed all of these phenotypes and enhanced homologous recombination. Our results suggest that after homologous pairing, the relative activity levels of Din7 and Mhr1 modulate the preference for replication versus homologous recombination to repair DSBs at ori5. PMID:23598996

Din7 and Mhr1 expression levels regulate double-strand-break-induced replication and recombination of mtDNA at ori5 in yeast.

PubMed

Ling, Feng; Hori, Akiko; Yoshitani, Ayako; Niu, Rong; Yoshida, Minoru; Shibata, Takehiko

2013-06-01

The Ntg1 and Mhr1 proteins initiate rolling-circle mitochondrial (mt) DNA replication to achieve homoplasmy, and they also induce homologous recombination to maintain mitochondrial genome integrity. Although replication and recombination profoundly influence mitochondrial inheritance, the regulatory mechanisms that determine the choice between these pathways remain unknown. In Saccharomyces cerevisiae, double-strand breaks (DSBs) introduced by Ntg1 at the mitochondrial replication origin ori5 induce homologous DNA pairing by Mhr1, and reactive oxygen species (ROS) enhance production of DSBs. Here, we show that a mitochondrial nuclease encoded by the nuclear gene DIN7 (DNA damage inducible gene) has 5'-exodeoxyribonuclease activity. Using a small ρ(-) mtDNA bearing ori5 (hypersuppressive; HS) as a model mtDNA, we revealed that DIN7 is required for ROS-enhanced mtDNA replication and recombination that are both induced at ori5. Din7 overproduction enhanced Mhr1-dependent mtDNA replication and increased the number of residual DSBs at ori5 in HS-ρ(-) cells and increased deletion mutagenesis at the ori5 region in ρ(+) cells. However, simultaneous overproduction of Mhr1 suppressed all of these phenotypes and enhanced homologous recombination. Our results suggest that after homologous pairing, the relative activity levels of Din7 and Mhr1 modulate the preference for replication versus homologous recombination to repair DSBs at ori5.

KIR Diversity in Māori and Polynesians: Populations in which HLA-B is not a Significant KIR Ligand

PubMed Central

Nemat-Gorgani, Neda; Edinur, Hisham A.; Hollenbach, Jill A.; Traherne, James A.; Dunn, Paul P. J.; Chambers, Geoffrey K.; Parham, Peter; Norman, Paul J.

2014-01-01

HLA class I molecules and killer cell immunoglobulin-like receptors (KIR) form a diverse system of ligands and receptors that individualize human immune systems in ways that improve the survival of individuals and populations. Human settlement of Oceania by island-hopping East and Southeast Asian migrants started ~3,500 years ago. Subsequently, New Zealand was reached ~750 years ago by ancestral Māori. To examine how this history impacted KIR and HLA diversity, and their functional interaction, we defined at high resolution the allelic and haplotype diversity of the 13 expressed KIR genes in 49 Māori and 34 Polynesians. Eighty KIR variants, including four ‘new’ alleles, were defined; as were 35 centromeric and 22 telomeric KIR region haplotypes, which combine to give >50 full-length KIR haplotypes. Two new and divergent variant KIR form part of a telomeric KIR haplotype, which appears derived from Papua New Guinea and was probably obtained by the Asian migrants en route to Polynesia. Māori and Polynesian KIR are very similar, but differ significantly from African, European, Japanese and Amerindian KIR. Māori and Polynesians have high KIR haplotype diversity with corresponding allotype diversity being maintained throughout the KIR locus. Within the population each individual has a unique combination of HLA class I and KIR. Characterizing Māori and Polynesians is a paucity of HLA-B allotypes recognized by KIR. Compensating for this deficiency are high frequencies (>50%) of HLA-A allotypes recognized by KIR. These HLA-A allotypes are ones that modern humans likely acquired from archaic humans at a much earlier time. PMID:25139336

Streptococcus gordonii DL1 adhesin SspB V-region mediates coaggregation via receptor polysaccharide of Actinomyces oris T14V.

PubMed

Back, C R; Douglas, S K; Emerson, J E; Nobbs, A H; Jenkinson, H F

2015-10-01

Streptococcus gordonii SspA and SspB proteins, members of the antigen I/II (AgI/II) family of Streptococcus adhesins, mediate adherence to cysteine-rich scavenger glycoprotein gp340 and cells of other oral microbial species. In this article we investigated further the mechanism of coaggregation between S. gordonii DL1 and Actinomyces oris T14V. Previous mutational analysis of S. gordonii suggested that SspB was necessary for coaggregation with A. oris T14V. We have confirmed this by showing that Lactococcus lactis surrogate host cells expressing SspB coaggregated with A. oris T14V and PK606 cells, while L. lactis cells expressing SspA did not. Coaggregation occurred independently of expression of A. oris type 1 (FimP) or type 2 (FimA) fimbriae. Polysaccharide was prepared from cells of A. oris T14V and found to contain 1,4-, 4,6- and 3,4-linked glucose, 1,4-linked mannose, and 2,4-linked galactose residues. When immobilized onto plastic wells this polysaccharide supported binding of L. lactis expressing SspB, but not binding of L. lactis expressing other AgI/II family proteins. Purified recombinant NAVP region of SspB, comprising amino acid (aa) residues 41-847, bound A. oris polysaccharide but the C-domain (932-1470 aa residues) did not. A site-directed deletion of 29 aa residues (Δ691-718) close to the predicted binding cleft within the SspB V-region ablated binding of the NAVP region to polysaccharide. These results infer that the V-region head of SspB recognizes an actinomyces polysaccharide ligand, so further characterizing a lectin-like coaggregation mechanism occurring between two important primary colonizers. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Myopotential inhibition of a bipolar pacemaker caused by electrode insulation defect.

PubMed Central

Amikam, S; Peleg, H; Lemer, J; Riss, E

1977-01-01

A patient is described in whom myopotentials orginating from the anterior abdominal wall muscle suppressed the implanted demand pacemaker despite its bipolar mode of action. This phenomenon was shown by simultaneous recording of the electrocardiogram the electromyogram. At operation, a defect in the insulation of a previously repaired epicardial electrode was found lying in close proximity to these muscles. After repair of the insulation defect, normal pacemaker function was restored. It is suggested that the myopotentials leaked into the pacing system through the insulation defect, thereby suppressing the demand unit, which maintained its bipolar mode of pacing throughout. Images PMID:145229

42 CFR 93.315 - Notice to ORI of institutional findings and actions.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Final institutional action. State whether the institution found research misconduct, and if so, who... 42 Public Health 1 2011-10-01 2011-10-01 false Notice to ORI of institutional findings and actions... HEALTH SERVICE POLICIES ON RESEARCH MISCONDUCT Responsibilities of Institutions The Institutional...

42 CFR 93.315 - Notice to ORI of institutional findings and actions.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Final institutional action. State whether the institution found research misconduct, and if so, who... 42 Public Health 1 2010-10-01 2010-10-01 false Notice to ORI of institutional findings and actions... HEALTH SERVICE POLICIES ON RESEARCH MISCONDUCT Responsibilities of Institutions The Institutional...

X-Raying the Beating Heart of a Newborn Star: Rotational Modulation of High-Energy Radiation from V1647 Ori

NASA Technical Reports Server (NTRS)

Hamaguchi, Kenji; Grosso, Nicolas; Kastner, Joel H.; Weintraub, David A.; Richmond, Michael; Petre, Robert; Teets, William K.; Principe, David

2012-01-01

We report a periodicity of approx.1 day in the highly elevated X-ray emission from the protostar V1647 Ori during its two recent multiple-year outbursts of mass accretion. This periodicity is indicative of protostellar rotation at near-breakup speed. Modeling of the phased X-ray light curve indicates the high-temperature ( 50 MK), X-ray-emitting plasma, which is most likely heated by accretion-induced magnetic reconnection, resides in dense ( 5 1010 cm.3), pancake-shaped magnetic footprints where the accretion stream feeds the newborn star. The sustained X-ray periodicity of V1647 Ori demonstrates that such protostellar magnetospheric accretion configurations can be stable over timescales of years. Subject headings: stars: formation stars: individual (V1647 Ori) stars: pre-main sequence X-rays: stars

High incidence of medulloblastoma in Māori and Pacific populations in New Zealand.

PubMed

Elwood, J Mark; Aye, Phyu Sin

2017-02-17

In New Zealand from 1995-2010, the incidence of medulloblastoma at ages 1-19 years was significantly higher in Māori (relative risk 2.0) and in Pacific peoples (RR 2.1) than in New Zealand Europeans.

Ethnic density and area deprivation: neighbourhood effects on Māori health and racial discrimination in Aotearoa/New Zealand.

PubMed

Bécares, Laia; Cormack, Donna; Harris, Ricci

2013-07-01

Some studies suggest that ethnic minority people are healthier when they live in areas with a higher concentration of people from their own ethnic group, a so-called ethnic density effect. To date, no studies have examined the ethnic density effect among indigenous peoples, for whom connections to land, patterns of settlement, and drivers of residential location may differ from ethnic minority populations. The present study analysed the Māori sample from the 2006/07 New Zealand Health Survey to examine the association between increased Māori ethnic density, area deprivation, health, and experiences of racial discrimination. Results of multilevel regressions showed that an increase in Māori ethnic density was associated with decreased odds of reporting poor self-rated health, doctor-diagnosed common mental disorders, and experienced racial discrimination. These associations were strengthened after adjusting for area deprivation, which was consistently associated with increased odds of reporting poor health and reports of racial discrimination. Our findings show that whereas ethnic density is protective of the health and exposure to racial discrimination of Māori, this effect is concealed by the detrimental effect of area deprivation, signalling that the benefits of ethnic density must be interpreted within the current socio-political context. This includes the institutional structures and racist practices that have created existing health and socioeconomic inequities in the first place, and maintain the unequal distribution of concentrated poverty in areas of high Māori density. Addressing poverty and the inequitable distribution of socioeconomic resources by ethnicity and place in New Zealand is vital to improving health and reducing inequalities. Given the racialised nature of access to goods, services, and opportunities within New Zealand society, this also requires a strong commitment to eliminating racism. Such commitment and action will allow the benefits

A chimeric protein composed of NuMA fused to the DNA binding domain of LANA is sufficient for the ori-P-dependent DNA replication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohsaki, Eriko; Ueda, Keiji, E-mail: kueda@virus.me

The Kaposi's sarcoma-associated herpesvirus (KSHV) genome is stably maintained in KSHV-infected PEL cell lines during cell division. We previously showed that accumulation of LANA in the nuclear matrix fraction could be important for the latent DNA replication, and that the functional significance of LANA should be its recruitment of ori-P to the nuclear matrix. Here, we investigated whether the forced localization of the LANA-DNA binding domain (DBD) to the nuclear matrix facilitated ori-P-containing plasmid replication. We demonstrated that chimeric proteins constructed by fusion of LANA DBD with the nuclear mitotic apparatus protein (NuMA), which is one of the components ofmore » the nuclear matrix, could bind with ori-P and enhance replication of an ori-P-containing plasmid, compared with that in the presence of DBD alone. These results further suggested that the ori-P recruitment to the nuclear matrix through the binding with DBD is important for latent viral DNA replication. - Highlights: •KSHV replication in latency depends on LANA localization to the nuclear matrix. •LANA DBD was fused with NuMA, a nuclear matrix protein, at the N- and C-terminus. •NuMA-DBD was in the nuclear matrix and supported the ori-P dependent replication. •LANA in the nuclear matrix should be important for the KSHV replication in latency.« less

The protective influence of family connectedness, ethnic identity, and ethnic engagement for New Zealand Ma̅ori adolescents.

PubMed

Stuart, Jaimee; Jose, Paul E

2014-06-01

The present study examined the associations among family connectedness, ethnic identity, and ethnic engagement on changes in well-being over time for the understudied population of Ma̅ori (indigenous New Zealand) youth. Data were collected as part of a longitudinal study of youth connectedness in New Zealand using self-report measures at 3 measurement occasions separated by 1 year each. Participants in the current study were 431 self-identified Ma̅ori (ages 10-15 years at Time 1). As expected, the variables of family connectedness, ethnic identity, and well-being were all positively related to each other. Results of a latent growth curve model showed that, following normative trends for adolescents of this age, well-being diminished over time for Ma̅ori youth; however, high levels of family connectedness were found to mitigate this general decline in well-being over time. Furthermore, in a longitudinal path analysis, ethnic engagement was found to exert a positive indirect effect on residualized Time 3 well-being through Time 2 ethnic identity. These findings indicate that the quality of family relationships and affiliation with one's ethnic group are important predictors of positive adjustment for Ma̅ori youth over time. These results are discussed in the context of positive youth development for ethnic minority and indigenous youth. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Whakaora nga moemoea o nga tupuna--living the dreams of the ancestors. Future planning in a Kaupapa Māori CAMHS team.

PubMed

Elder, Hinemoa; Milne, Moe; Witehira, Heemi; Mendes, Patrick; Heslin, Anneliese; Cribb-Su'a, Ainsleigh; Wilson, Riwai; Goldsmith, Arona; Kainamu, Reena; Barrett, Moana; Love, Shar; Cargo, Tania; Kalra, Vanitha

2009-08-01

The aim of this study was to identify and operationalize aspects of a future planning process for sustainable delivery of Kaupapa Māori (Specialist Māori) mental health from a team called He Kakano, within Child and Adolescent Mental Health Services in South Auckland, New Zealand. A 2-day hui (meeting) was held with members of the team and a facilitator, Whaea Moe Milne. Review of background national epidemiological data, local data, information from community, carer and tangata whaiora (consumer) stakeholders and the existing He Kakano Model of Care was undertaken. Use of tikanga (Māori protocol and practices) was evident throughout the hui. A number of aspects of tikanga were identified as essential to the positive outcomes of the future plan. This paper reports one in particular, that of whakatauakī (proverbs where the originator is known). "Whakaora nga moemoea o nga tupuna--living the dreams of the ancestors" is a whakatauakī articulated by Whaea Moe Milne, which was identified as helpful in influencing the strategic planning thinking and decision-making process for He Kakano. This whakatauakī enabled the identification of shared goals, values, beliefs, behaviours and an action plan. The existing and ongoing relationship with Whaea Moe Milne was identified as an important element in the way in which the whakatauakī was received and reflected on. Use of tikanga Māori, in this case, whakatauakī, was helpful in developing future planning for He Kakano. This suggests that use of tikanga may be beneficial in other settings where planning for sustainable Māori responsive services is undertaken. Further work in this area is likely to benefit service development, strategic planning, workforce development and have an impact on improving health outcomes for Māori.

Muscle-derived Decellularised Extracellular Matrix Improves Functional Recovery in a Rat Latissimus Dorsi Muscle Defect Model

DTIC Science & Technology

2013-12-01

battlefield wounds, often involving volumetric muscle loss (VML). The physical loss of muscle results in functional deficits and cosmetic ...repair with M-ECM and 3) sham (all procedures except muscle excision). Four and 8 weeks post- surgery , the isometric contractile properties of the LD... Surgery (2013) 66, 1750e1758 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is

Postpartum pelvic floor muscle training and urinary incontinence: a randomized controlled trial.

PubMed

Hilde, Gunvor; Stær-Jensen, Jette; Siafarikas, Franziska; Ellström Engh, Marie; Bø, Kari

2013-12-01

To evaluate whether postpartum pelvic floor muscle training decrease prevalence of any urinary incontinence (UI) in primiparous women with and without UI at inclusion (mixed population) and further to perform stratified analyses on women with and without major levator ani muscle defects. A two-armed assessor-blinded randomized controlled trial including primiparous women 6 weeks after vaginal delivery was conducted. Participants were stratified on major levator ani muscle defects, verified by transperineal ultrasonography, and thereafter randomly allocated to training or control. All participants were taught to contract the pelvic floor muscles. The control participants received no further intervention, whereas training participants attended a weekly supervised pelvic floor muscle training class and performed daily home exercise for 16 weeks. Primary outcome was self-reported UI analyzed by relative risk. We included 175 women, 55 with major levator ani muscle defects and 120 without. Prevalence of UI at baseline was 39.1% in the training group (n=87) and 50% among those in the control group (n=88). Fifteen women (8.6%) were lost to follow-up. At 6 months after delivery (postintervention), 34.5% and 38.6% reported UI in the training and control groups, respectively. Relative risk analysis of UI gave a nonsignificant effect size of 0.89 (95% confidence interval [CI] 0.60-1.32). Results were similar for the stratum with and without major levator ani muscle defects, 0.89 (95% CI 0.51-1.56) and 0.90 (95% CI 0.53-1.52), respectively. Postpartum pelvic floor training did not decrease UI prevalence 6 months after delivery in primiparous women. Stratified analysis on women with and without major levator ani muscle defects showed similar nonsignificant results. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01069484. : I.

The Combating Obesity in Māori and Pasifika Adolescent School-Children Study: COMPASS Methodology and Study Protocol

PubMed Central

Stoner, Lee; Shultz, Sarah P.; Lambrick, Danielle M.; Krebs, Jeremy; Weatherall, Mark; Palmer, Barry R.; Lane, Andrew M.; Kira, Geoff; Witter, Trevor; Williams, Michelle A.

2013-01-01

Background: Lifestyle modifications including, physical activity can reduce obesity-related morbidity and subsequent cardiovascular disease in youth. This study will investigate the efficacy of a culturally-sensitive, non-contact, boxing-orientated training program on obesity and related cardio-metabolic conditions in Māori and Pasifika adolescents. Details of the methodological aspects of recruitment, inclusion criteria, randomization, cultural sensitivity, intervention program, assessments, process evaluation, and statistical analyses are described. Methods: This study will be a community based, New Zealand, randomized control trial (RCT). Male and female obese (body mass index >95th percentile) Māori and Pasifika adolescents aged 14-16 years will be recruited and the sample size will be confirmed through a feasibility study. Combating Obesity in Māori and Pasifika Adolescent School-children Study (COMPASS) is a 6-month, theory-based program, conducted 3-times/week in a culturally appropriate setting. Each session includes 40 min boxing-orientated training and 30 min resistance training. Assessments will be made at baseline, 3-months, 6-months, 12-months, and 24-months. Main outcomes include abdominal obesity, endothelial function, and insulin resistance. Other outcomes include arterial stiffness, lipid profile, inflammatory biomarkers, well-being, and aerobic fitness. Control measures include physical activity, sleep behavior, and dietary intake. Results: As a protocol paper there are no specific results to present, our purpose is to share our RCT design with the scientific community. Conclusions: COMPASS will be used to provide direction for exercise prescription policy in at-risk Māori and Pasifika adolescents. PMID:23930168

Māori oral histories and the impact of tsunamis in Aotearoa-New Zealand

NASA Astrophysics Data System (ADS)

King, Darren N.; Shaw, Wendy S.; Meihana, Peter N.; Goff, James R.

2018-03-01

Māori oral histories from the northern South Island of Aotearoa-New Zealand provide details of ancestral experience with tsunami(s) on, and surrounding, Rangitoto (D'Urville Island). Applying an inductive-based methodology informed by collaborative storytelling, exchanges with key informants from the Māori kin groups of Ngāti Koata and Ngāti Kuia reveal that a folk tale, published in 1907, could be compared to and combined with active oral histories to provide insights into past catastrophic saltwater inundations. Such histories reference multiple layers of experience and meaning, from memorials to ancestral figures and their accomplishments to claims about place, authority and knowledge. Members of Ngāti Koata and Ngāti Kuia, who permitted us to record some of their histories, share the view that there are multiple benefits to be gained by learning from differences in knowledge, practice and belief. This work adds to scientific as well as Maōri understandings about tsunami hazards (and histories). It also demonstrates that to engage with Māori oral histories (and the people who genealogically link to such stories) requires close attention to a politics of representation, in both past recordings and current ways of retelling, as well as sensitivities to the production of new and plural knowledges. This paper makes these narratives available to a new audience, including those families who no longer have access to them, and recites these in ways that might encourage plural knowledge development and co-existence.

Role of the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand Māori, Pacific Island, and Caucasian case-control sample sets.

PubMed

Hollis-Moffatt, Jade E; Xu, Xin; Dalbeth, Nicola; Merriman, Marilyn E; Topless, Ruth; Waddell, Chloe; Gow, Peter J; Harrison, Andrew A; Highton, John; Jones, Peter B B; Stamp, Lisa K; Merriman, Tony R

2009-11-01

To examine the role of genetic variation in the renal urate transporter SLC2A9 in gout in New Zealand sample sets of Māori, Pacific Island, and Caucasian ancestry and to determine if the Māori and Pacific Island samples could be useful for fine-mapping. Patients (n= 56 Māori, 69 Pacific Island, and 131 Caucasian) were recruited from rheumatology outpatient clinics and satisfied the American College of Rheumatology criteria for gout. The control samples comprised 125 Māori subjects, 41 Pacific Island subjects, and 568 Caucasian subjects without arthritis. SLC2A9 single-nucleotide polymorphisms rs16890979 (V253I), rs5028843, rs11942223, and rs12510549 were genotyped (possible etiologic variants in Caucasians). Association of the major allele of rs16890979, rs11942223, and rs5028843 with gout was observed in all sample sets (P = 3.7 x 10(-7), 1.6 x 10(-6), and 7.6 x 10(-5) for rs11942223 in the Māori, Pacific Island, and Caucasian samples, respectively). One 4-marker haplotype (1/1/2/1; more prevalent in the Māori and Pacific Island control samples) was not observed in a single gout case. Our data confirm a role of SLC2A9 in gout susceptibility in a New Zealand Caucasian sample set, with the effect on risk (odds ratio >2.0) greater than previous estimates. We also demonstrate association of SLC2A9 with gout in samples of Māori and Pacific Island ancestry and a consistent pattern of haplotype association. The presence of both alleles of rs16890979 on susceptibility and protective haplotypes in the Māori and Pacific Island sample is evidence against a role for this nonsynonymous variant as the sole etiologic agent. More extensive linkage disequilibrium in Māori and Pacific Island samples suggests that Caucasian samples may be more useful for fine-mapping.

Titration of DnaA protein by oriC DnaA-boxes increases dnaA gene expression in Escherichia coli.

PubMed Central

Hansen, F G; Koefoed, S; Sørensen, L; Atlung, T

1987-01-01

Binding of the DnaA protein to its binding sites, the DnaA-boxes (TTATCCACA), was measured by a simple physiological approach. The presence of extra DnaA-boxes in growing cells leads to a derepression of dnaA gene expression, measured as beta-galactosidase activity of a dnaA-lacZ fusion polypeptide. Different DnaA-boxes caused different degrees of derepression indicating that the DnaA protein requires sequences in addition to the DnaA-box for efficient binding. The DnaA-boxes in oriC might act cooperatively in binding of the DnaA protein. The derepressed levels of DnaA protein obtained in a strain carrying an oriC+-pBR322 chimera were very high and sufficient to activate oriC on the chimeric plasmid, which was maintained at a copy number more than three times that of pBR322. PMID:3034578

Patent ductus arteriosus in mice with smooth muscle-specific Jag1 deletion

PubMed Central

Feng, Xuesong; Krebs, Luke T.; Gridley, Thomas

2010-01-01

The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus and is one of the most common congenital heart defects. Mice with smooth muscle cell-specific deletion of Jag1, which encodes a Notch ligand, die postnatally from patent ductus arteriosus. These mice exhibit defects in contractile smooth muscle cell differentiation in the vascular wall of the ductus arteriosus and adjacent descending aorta. These defects arise through an inability to propagate the JAG1-Notch signal via lateral induction throughout the width of the vascular wall. Both heterotypic endothelial smooth muscle cell interactions and homotypic vascular smooth muscle cell interactions are required for normal patterning and differentiation of the ductus arteriosus and adjacent descending aorta. This new model for a common congenital heart defect provides novel insights into the genetic programs that underlie ductus arteriosus development and closure. PMID:21068062

Orbital Solution for the Spectroscopic Binary in the GW Ori Hierarchical Triple

NASA Astrophysics Data System (ADS)

Prato, L.; Ruíz-Rodríguez, Dary; Wasserman, L. H.

2018-01-01

We present the first double-lined orbital solution for the close binary in the GW Ori triple system. Using 12 epochs of infrared spectroscopy, we detected the lines of both stars in the inner pair, previously known as single-lined only. Our preliminary infrared orbital solution has an eccentricity of e = 0.21 ± 0.10, a period of P = 241.15 ± 0.72 days, and a mass ratio of q = 0.66 ± 0.13. We find a larger semi-amplitude for the primary star, K1 = 6.57 ± 1.00 km s‑1, with an infrared-only solution compared to K1 = 4.41 ± 0.33 km s‑1 with optical data from the literature, likely the result of line blending and veiling in the optical. The component spectral types correspond to G3 and K0 stars, with v\\sin i values of 43 km s‑1 and 50 km s‑1, respectively. We obtained a flux ratio of α = 0.58 ± 0.14 in the H-band, allowing us to estimate individual masses of 3.2 and 2.7 M ⊙ for the primary and secondary, respectively, using evolutionary tracks. The tracks also yield a coeval age of 1 Myr for both components to within 1σ. GW Ori is surrounded by a circumbinary/circumtriple disk. A tertiary component has been detected in previous studies; however, we did not detect this component in our near-infrared spectra, probably the result of its relative faintness and blending in the absorption lines of these rapidly rotating stars. With these results, GW Ori joins the small number of classical T Tauri, double-lined spectroscopic binaries.

Māori patients' experiences and perspectives of chronic kidney disease: a New Zealand qualitative interview study.

PubMed

Walker, Rachael C; Walker, Shayne; Morton, Rachael L; Tong, Allison; Howard, Kirsten; Palmer, Suetonia C

2017-01-19

To explore and describe Māori (the indigenous people of New Zealand) patients' experiences and perspectives of chronic kidney disease (CKD), as these are largely unknown for indigenous groups with CKD. Face-to-face, semistructured interviews with purposive sampling and thematic analysis. 3 dialysis centres in New Zealand (NZ), all of which offered all forms of dialysis modalities. 13 Māori patients with CKD and who were either nearing the need for dialysis or had started dialysis within the previous 12 months. The Māori concepts of whakamā (disempowerment and embarrassment) and whakamana (sense of self-esteem and self-determination) provided an overarching framework for interpreting the themes identified: disempowered by delayed CKD diagnosis (resentment of late diagnosis; missed opportunities for preventive care; regret and self-blame); confronting the stigma of kidney disease (multigenerational trepidation; shame and embarrassment; fear and denial); developing and sustaining relationships to support treatment decision-making (importance of family/whānau; valuing peer support; building clinician-patient trust); and maintaining cultural identity (spiritual connection to land; and upholding inner strength/mana). Māori patients with CKD experienced marginalisation within the NZ healthcare system due to delayed diagnosis, a focus on individuals rather than family, multigenerational fear of dialysis, and an awareness that clinicians are not aware of cultural considerations and values during decision-making. Prompt diagnosis to facilitate self-management and foster trust between patients and clinicians, involvement of family and peers in dialysis care, and acknowledging patient values could strengthen patient engagement and align decision-making with patient priorities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Relating Radiative Fluxes on Arctic Sea Ice Area Using Arctic Observation and Reanalysis Integrated System (ArORIS)

NASA Astrophysics Data System (ADS)

Sledd, A.; L'Ecuyer, T. S.

2017-12-01

With Arctic sea ice declining rapidly and Arctic temperatures rising faster than the rest of the globe, a better understanding of the Arctic climate, and ice cover-radiation feedbacks in particular, is needed. Here we present the Arctic Observation and Reanalysis Integrated System (ArORIS), a dataset of integrated products to facilitate studying the Arctic using satellite, reanalysis, and in-situ datasets. The data include cloud properties, radiative fluxes, aerosols, meteorology, precipitation, and surface properties, to name just a few. Each dataset has uniform grid-spacing, time-averaging and naming conventions for ease of use between products. One intended use of ArORIS is to assess Arctic radiation and moisture budgets. Following that goal, we use observations from ArORIS - CERES-EBAF radiative fluxes and NSIDC sea ice fraction and area to quantify relationships between the Arctic energy balance and surface properties. We find a discernable difference between energy budgets for years with high and low September sea ice areas. Surface fluxes are especially responsive to the September sea ice minimum in months both leading up to September and the months following. In particular, longwave fluxes at the surface show increased sensitivity in the months preceding September. Using a single-layer model of solar radiation we also investigate the individual responses of surface and planetary albedos to changes in sea ice area. By partitioning the planetary albedo into surface and atmospheric contributions, we find that the atmospheric contribution to planetary albedo is less sensitive to changes in sea ice area than the surface contribution. Further comparisons between observations and reanalyses can be made using the available datasets in ArORIS.

Reconstruction with latissimus dorsi, external abdominal oblique and cranial sartorius muscle flaps for a large defect of abdominal wall in a dog after surgical removal of infiltrative lipoma

PubMed Central

FENG, Yu-Ching; CHEN, Kuan-Sheng; CHANG, Shih-Chieh

2016-01-01

This animal was presented with a large-sized infiltrative lipoma in the abdominal wall that had been noted for 4 years. This lipoma was confirmed by histological examination from a previous biopsy, and the infiltrative features were identified by a computerized tomography scan. The surgical removal created a large-sized abdominal defect that was closed by a combination of latissimus dorsi and external abdominal oblique muscle flaps in a pedicle pattern. A small dehiscence at the most distal end of the muscle flap resulted in a small-sized abdominal hernia and was repaired with cranial sartorius muscle flap 14 days after surgery. The dog was in good general health with no signs of tumor recurrence after 18 months of follow-up. PMID:27476526

Exercise Promotes Healthy Aging of Skeletal Muscle

PubMed Central

Cartee, Gregory D.; Hepple, Russell T.; Bamman, Marcas M.; Zierath, Juleen R.

2016-01-01

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics, and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes “healthy aging” by inducing modifications in skeletal muscle. PMID:27304505

Anatomy and surgical treatment of the depressor septi nasi muscle: a systematic review.

PubMed

Sinno, Sammy; Chang, Jessica B; Saadeh, Pierre B; Lee, Michael R

2015-05-01

Although the majority of nasal alterations in rhinoplasty result from either augmentation or reduction of bone and cartilaginous substructure, modifications of influential soft-tissue provide significant contribution to the final result. The depressor septi nasi muscle is a soft-tissue structure well known to influence the final result in rhinoplasty. The objective of this study was to perform a standardized, comprehensive review of relevant data published with regard to the depressor septi nasi muscle. A comprehensive search of the terms "depressor septi muscle" and "depressor septi nasi muscle" was performed using the PubMed, MEDLINE, and Cochrane databases. Articles were reviewed for relevancy and included if criteria were met. A secondary review was performed of all articles cited, to maximize diligence. Forty-three articles were identified in the initial search. Thirteen of the 43 were found to meet inclusion criteria. Secondary search revealed additional studies meeting inclusion criteria. Altogether, there were 175 cadaver specimens and 821 surgically treated patients for which data were available. Anatomical reports and nomenclature were found to vary. Surgical approach and muscle treatment diverged, with objective data showing no superior method. Although variation exists in anatomical reports regarding the depressor septi nasi muscle, the prevailing thought is that it originates from the maxilla and/or orbicularis oris muscle. More importantly, the muscle inserts on the medial crura and adjacent soft tissue. Disruption of this relationship provides the basis for surgical treatment of tip descent on animation.

Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit.

PubMed

Ruvinsky, Igor; Katz, Maximiliano; Dreazen, Avigail; Gielchinsky, Yuval; Saada, Ann; Freedman, Nanette; Mishani, Eyal; Zimmerman, Gabriel; Kasir, Judith; Meyuhas, Oded

2009-05-19

Mice, whose ribosomal protein S6 cannot be phosphorylated due to replacement of all five phosphorylatable serine residues by alanines (rpS6(P-/-)), are viable and fertile. However, phenotypic characterization of these mice and embryo fibroblasts derived from them, has established the role of these modifications in the regulation of the size of several cell types, as well as pancreatic beta-cell function and glucose homeostasis. A relatively passive behavior of these mice has raised the possibility that they suffer from muscle weakness, which has, indeed, been confirmed by a variety of physical performance tests. A large variety of experimental methodologies, including morphometric measurements of histological preparations, high throughput proteomic analysis, positron emission tomography (PET) and numerous biochemical assays, were used in an attempt to establish the mechanism underlying the relative weakness of rpS6(P-/-) muscles. Collectively, these experiments have demonstrated that the physical inferiority appears to result from two defects: a) a decrease in total muscle mass that reflects impaired growth, rather than aberrant differentiation of myofibers, as well as a diminished abundance of contractile proteins; and b) a reduced content of ATP and phosphocreatine, two readily available energy sources. The abundance of three mitochondrial proteins has been shown to diminish in the knockin mouse. However, the apparent energy deficiency in this genotype does not result from a lower mitochondrial mass or compromised activity of enzymes of the oxidative phosphorylation, nor does it reflect a decline in insulin-dependent glucose uptake, or diminution in storage of glycogen or triacylglycerol (TG) in the muscle. This study establishes rpS6 phosphorylation as a determinant of muscle strength through its role in regulation of myofiber growth and energy content. Interestingly, a similar role has been assigned for ribosomal protein S6 kinase 1, even though it regulates

Localized DNA melting and structural pertubations in the origin of replication, oriC, of Escherichia coli in vitro and in vivo.

PubMed Central

Gille, H; Messer, W

1991-01-01

The leftmost region of the Escherichia coli origin of DNA replication (oriC) contains three tandemly repeated AT-rich 13mers which have been shown to become single-stranded during the early stages of initiation in vitro. Melting is induced by the ATP form of DnaA, the initiator protein of DNA replication. KMnO4 was used to probe for single-stranded regions and altered DNA conformation during the initiation of DNA replication at oriC in vitro and in vivo. Unpairing in the AT-rich 13mer region is thermodynamically stable even in the absence of DnaA protein, but only when divalent cations are omitted from the reaction. In the presence of Mg2+, oriC melting is strictly DnaA dependent. The sensitive region is distinct from that detected in the absence of DnaA as it is located further to the left within the minimal origin. In addition, the DNA is severely distorted between the three 13mers and the IHF binding site in oriC. A change of conformation can also be observed during the initiation of DNA replication in vivo. This is the first in vivo evidence for a structural change at the 13mers during initiation complex formation. Images PMID:2026151

[Cayler syndrome: A case report and review of the literature].

PubMed

Bellaiche, J; Correia, N; Bouche Pillon Persyn, M A; Chiriac, S; Bodin, F; François, C

2016-08-01

Facial asymmetries to the tears are rare. We report a pediatric original case that may fall within the framework of a Cayler syndrome. Through its clinical presentation, we will discuss differential diagnoses, associated forms, its etiology, and its management. At the maternity unit, in a male infant, after vaginal delivery at term without extraction, was discovered a lack of mobility of the labial commissure on the right side, only when crying. The rest of the examination was unremarkable, except ipsilateral microtia. Genetically, karyotype was 46,XY, 22q11 without microdeletion. The head and neck MRI and echocardiogram were normal. Asymmetry with tears has been described in the literature, through association with microdeletion 22q11 syndrome. The originality of this case was the presence of an isolated muscle abnormality. Muscles affected by this syndrome are: Musculus depressor labii inferioris, the Depressor anguli oris, and Mentalis musculus. The three muscles can be affected concomitantly. Isolated involvment of the Depressor anguli oris muscle has also been described. The mechanical dysfunction can be either linked to muscle innervation agenesis or to a defect thereof. There is no specific treatment. The symptoms improve with age by decreasing the frequency of crying. However, it is important to know this pathology in order to seek an optimum balance further in search of associated abnormalities (FISH 22q11, cardiac Doppler ultrasound) but also to educate, to reassure families often worried by the situation. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Development of oriC-Based Plasmids for Mesoplasma florum.

PubMed

Matteau, Dominick; Pepin, Marie-Eve; Baby, Vincent; Gauthier, Samuel; Arango Giraldo, Mélissa; Knight, Thomas F; Rodrigue, Sébastien

2017-04-01

The near-minimal bacterium Mesoplasma florum constitutes an attractive model for systems biology and for the development of a simplified cell chassis in synthetic biology. However, the lack of genetic engineering tools for this microorganism has limited our capacity to understand its basic biology and modify its genome. To address this issue, we have evaluated the susceptibility of M. florum to common antibiotics and developed the first generation of artificial plasmids able to replicate in this bacterium. Selected regions of the predicted M. florum chromosomal origin of replication ( oriC ) were used to create different plasmid versions that were tested for their transformation frequency and stability. Using polyethylene glycol-mediated transformation, we observed that plasmids harboring both rpmH-dnaA and dnaA-dnaN intergenic regions, interspaced or not with a copy of the dnaA gene, resulted in a frequency of ∼4.1 × 10 -6 transformants per viable cell and were stably maintained throughout multiple generations. In contrast, plasmids containing only one M. florum oriC intergenic region or the heterologous oriC region of Mycoplasma capricolum , Mycoplasma mycoides , or Spiroplasma citri failed to produce any detectable transformants. We also developed alternative transformation procedures based on electroporation and conjugation from Escherichia coli , reaching frequencies up to 7.87 × 10 -6 and 8.44 × 10 -7 transformants per viable cell, respectively. Finally, we demonstrated the functionality of antibiotic resistance genes active against tetracycline, puromycin, and spectinomycin/streptomycin in M. florum Taken together, these valuable genetic tools will facilitate efforts toward building an M. florum -based near-minimal cellular chassis for synthetic biology. IMPORTANCE Mesoplasma florum constitutes an attractive model for systems biology and for the development of a simplified cell chassis in synthetic biology. M. florum is closely related to the mycoides

How Indigenous values shaped a successful multi-year Soil Health program in Aotearoa-New Zealand (presented from both indigenous Māori and western science perspectives)

NASA Astrophysics Data System (ADS)

Stevenson, B.; Harmsworth, G.; Kalaugher, E.

2017-12-01

New Zealand is a multicultural society, founded on the Treaty of Waitangi which when enshrined into various legislation and national policy, provides incentive to incorporate indigenous Māori world views into nationally funded science and research programmes. Here we discuss how the integration of indigenous world views and western science were combined in a research proposal that resulted in successful funding for a 5 year collaborative science programme. The programme strives to develop an expanded national soil health framework for New Zealand that will be used by policy makers, local government, indigenous Māori, industry, and primary sector groups to maintain the natural capital and productivity of soils within environmental constraints. Soil health is fundamental to economic, social, and human wellbeing, and provides a myriad of ecosystem and environmental services, such as those sustaining food and fibre production. Typically soil health is defined by "dynamic" soil characteristics that are susceptible to changes in land use or land management over relatively short time frames (years to decades). Soil resilience, however, is a much longer-term concept that is not well captured in current soil health thinking. The Māori world view encapsulates such long term thinking through interconnected Māori values and inter-generational concepts (e.g., whakapapa, rangatiratanga, manawhenua, kaitiakitanga, mauri) that provide the basis for indigenous resource management in Aotearoa-New Zealand. These values and recognition of the Treaty of Waitangi provide authority and rights to manage resources according to tikanga (customs, principles). Māori environmental concepts and knowledge combined with science concepts for understanding soil health and resilience, served as a powerful central theme for the design and implementation of this science program. Māori involvement and capability development are integral to this research effort and we believe the synthesis of Māori

Delta Ori Phase-Dependent Variability from Chandra and MOST Campaign

NASA Astrophysics Data System (ADS)

Nichols, Joy; Naze, Yael; Moffatt, Anthony F. J.; Corcoran, Michael; Richardson, Noel; Williams, S.; Pollock, A. M. T.; Ignace, Richard; Hole, T.; Waldron, W.; Evans, Nancy Remage; MOST Collaboration

2013-06-01

We report preliminary results from variability analysis of delta Ori in Chandra high-resolution X-ray spectroscopy and concurrent MOST high-precision optical photometry. With nearly complete phase coverage of the 5-day eclipsing binary orbit, it is possible to measure directly radial velocity and flux variations as a function of phase, leading to a mapping of the stellar wind distribution for the massive primary star. The phase dependence of the X-ray overall intensity and the comparative behavior of the emission lines are also presented.

Exercise Promotes Healthy Aging of Skeletal Muscle.

PubMed

Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M; Zierath, Juleen R

2016-06-14

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle. Copyright © 2016 Elsevier Inc. All rights reserved.

Interkingdom cooperation between Candida albicans, Streptococcus oralis and Actinomyces oris modulates early biofilm development on denture material.

PubMed

Cavalcanti, Indira M G; Nobbs, Angela H; Ricomini-Filho, Antônio Pedro; Jenkinson, Howard F; Del Bel Cury, Altair A

2016-04-01

Candida-associated stomatitis affects up to 60% of denture wearers, and Candida albicans remains the most commonly isolated fungal species. The oral bacteria Actinomyces oris and Streptococcus oralis are abundant in early dental plaque. The aims of this study were to determine the effects of S. oralis and A. oris on the development of C. albicans biofilms on denture material. Resin discs were coated with saliva and at early (1.5 h) or later (24 h) stages of biofilm development, cell numbers of each species were determined. Spatial distribution of microorganisms was visualized by confocal scanning laser microscopy of biofilms labelled by differential fluorescence or by fluorescence in situ hybridization. Interkingdom interactions underpinning biofilm development were also evaluated planktonically utilizing fluorescence microscopy. Synergistic interactions between all three species occurred within biofilms and planktonically. Bacterial cells coaggregated with each other and adhered singly or in coaggregates to C. albicans hyphal filaments. Streptococcus oralis appeared to enhance hyphal filament production and C. albicans biovolume was increased 2-fold. Concomitantly, cell numbers of S. oralis and A. oris were enhanced by C. albicans. Thus, cooperative physical and metabolic processes occurring between these three microbial species intensify pathogenic plaque communities on denture surfaces. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

In vivo dynamics of EBNA1-oriP interaction during latent and lytic replication of Epstein-Barr virus.

PubMed

Daikoku, Tohru; Kudoh, Ayumi; Fujita, Masatoshi; Sugaya, Yutaka; Isomura, Hiroki; Tsurumi, Tatsuya

2004-12-24

The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is required for maintenance of the viral genome DNA during the latent phase of EBV replication but continues to be synthesized after the induction of viral productive replication. An EBV genome-wide chromatin immunoprecipitation assay revealed that EBNA1 constantly binds to oriP of the EBV genome during not only latent but also lytic infection. Although the total levels of EBNA1 proved constant throughout the latter, the levels of the oriP-bound form were increased as lytic infection proceeded. EBV productive DNA replication occurs at discrete sites in nuclei, called replication compartments, where viral replication proteins are clustered. Confocal laser microscopic analyses revealed that whereas EBNA1 was distributed broadly in nuclei as fine punctate dots during the latent phase of infection, the protein became redistributed to the viral replication compartments and localized as distinct spots within and/or nearby the compartments after the induction of lytic replication. Taking these findings into consideration, oriP regions of the EBV genome might be organized by EBNA1 into replication domains that may set up scaffolding for lytic replication and transcription.

How efficient are New Zealand's District Health Boards at producing life expectancy gains for Māori and Europeans?

PubMed

Sandiford, Peter; Consuelo, David Juan José Vivas; Rouse, Paul

2017-04-01

Use data envelopment analysis (DEA) to measure the efficiency of New Zealand's District Health Boards (DHBs) at achieving gains in Māori and European life expectancy (LE). Using life tables for 2006 and 2013, a two-output DEA model established the production possibility frontier for Māori and European LE gain. Confidence limits were generated from a 10,000 replicate Monte Carlo simulation. Results support the use of LE change as an indicator of DHB efficiency. DHB mean income and education were related to initial LE but not to its rate of change. LE gains were unrelated to either the initial level of life expectancy or to the proportion of Māori in the population. DHB efficiency ranged from 79% to 100%. Efficiency was significantly correlated with DHB financial performance. Changes in LE did not depend on the social characteristics of the DHB. The statistically significant association between efficiency and financial performance supports its use as an indicator of managerial effectiveness. Implications for public health: Efficient health systems achieve better population health outcomes. DEA can be used to measure the relative efficiency of sub-national health authorities at achieving health gain and equity outcomes. © 2016 The Authors.

Face-to-face versus telephone delivery of the Green Prescription for Māori and New Zealand Europeans with type-2 diabetes mellitus: influence on participation and health outcomes.

PubMed

Williams, Margaret; Cairns, Simeon; Simmons, David; Rush, Elaine

2017-11-10

In Aotearoa/New Zealand, the proportion of Māori who participate in the national Green Prescription lifestyle programme is lower than for New Zealand Europeans. We compared the uptake and effectiveness of two modes of Green Prescription delivery: face-to-face and telephone among both Māori and New Zealand Europeans. Sixty-eight Māori and 70 New Zealand Europeans with type-2 diabetes participated in this six-month randomised trial of the two modes of delivery. Recruitment integrated an explicitly Māori culturally sensitive approach. All participants received lifestyle intervention. Anthropometry, blood lipids and glycated haemoglobin were measured before and after the intervention. The face-to-face approach (first meeting) yielded 100% uptake into the programme among both Māori and New Zealand Europeans. At six months there were overall reductions in weight (1.8; [95 CI%, 0.6, 2.9kg]), waist circumference (3.7 [2.6, 4.8cm]), and total cholesterol (0.6 [0.3, 0.9mmol/l]) and glycated haemoglobin (3.1 [-0.2, 6.7mmol/mol]). There were no significant differences by mode of delivery, ethnicity or gender. The Green Prescription programme resulted in small but clinically favourable improvements in health outcomes for type-2 diabetes patients, regardless of the mode of delivery for both Māori and New Zealand Europeans.

Dietary intakes of European, Māori, Pacific and Asian adults living in Auckland: the Diabetes, Heart and Health Study.

PubMed

Metcalf, Patricia A; Scragg, Robert R K; Schaaf, David; Dyall, Lorna; Black, Peter N; Jackson, Rod

2008-10-01

To compare dietary intakes of European, Māori, Pacific, and Asian men and women living in Auckland. Daily nutrient intakes were calculated from a self-administered food frequency questionnaire from participants in a cross-sectional health screening study carried out between 2002 and 2003. Participants were 4,007 Māori, Pacific, Asian and European people (1,915 men, 2,092 women) aged 35 to 74 years. Compared with Europeans, Māori and Pacific men had higher total energy intakes per day, while Asians had lower intakes. A similar pattern was observed for carbohydrate and fat consumption. While protein and cholesterol consumption tended to be lower in Europeans than the other three ethnic groups, alcohol consumption and calcium intakes were highest among Europeans. Many of the differences between ethnic groups were attenuated when nutrient consumption was expressed as their percentage contribution to total energy intake suggesting that total food consumption was the major determinant of ethnic differences in nutrient intakes. There were substantial differences in dietary habits, food selections and cooking practices between European, Māori, Pacific and Asian participants. However, the observed differences were in the area of serving sizes and frequency of consumption of certain foods than to major differences in the range of foods and nutrients consumed or the percentage contribution of carbohydrate, fat or protein to total energy intake. The development of strategies to reduce serving sizes and the frequency of consumption of certain foods will be required to help address the major nutrition-related health problems in New Zealand.

Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis.

PubMed

Harel, Itamar; Maezawa, Yoshiro; Avraham, Roi; Rinon, Ariel; Ma, Hsiao-Yen; Cross, Joe W; Leviatan, Noam; Hegesh, Julius; Roy, Achira; Jacob-Hirsch, Jasmine; Rechavi, Gideon; Carvajal, Jaime; Tole, Shubha; Kioussi, Chrissa; Quaggin, Susan; Tzahor, Eldad

2012-11-13

The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.

Interactions between Streptococcus oralis, Actinomyces oris, and Candida albicans in the development of multispecies oral microbial biofilms on salivary pellicle.

PubMed

Cavalcanti, I M G; Del Bel Cury, A A; Jenkinson, H F; Nobbs, A H

2017-02-01

The fungus Candida albicans is carried orally and causes a range of superficial infections that may become systemic. Oral bacteria Actinomyces oris and Streptococcus oralis are abundant in early dental plaque and on oral mucosa. The aims of this study were to determine the mechanisms by which S. oralis and A. oris interact with each other and with C. albicans in biofilm development. Spatial distribution of microorganisms was visualized by confocal laser scanning microscopy of biofilms labeled by differential fluorescence or by fluorescence in situ hybridization (FISH). Actinomyces oris and S. oralis formed robust dual-species biofilms, or three-species biofilms with C. albicans. The bacterial components tended to dominate the lower levels of the biofilms while C. albicans occupied the upper levels. Non-fimbriated A. oris was compromised in biofilm formation in the absence or presence of streptococci, but was incorporated into upper biofilm layers through binding to C. albicans. Biofilm growth and hyphal filament production by C. albicans was enhanced by S. oralis. It is suggested that the interkingdom biofilms are metabolically coordinated to house all three components, and this study demonstrates that adhesive interactions between them determine spatial distribution and biofilm architecture. The physical and chemical communication processes occurring in these communities potentially augment C. albicans persistence at multiple oral cavity sites. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nebulin deficiency in adult muscle causes sarcomere defects and muscle-type-dependent changes in trophicity: novel insights in nemaline myopathy

PubMed Central

Li, Frank; Buck, Danielle; De Winter, Josine; Kolb, Justin; Meng, Hui; Birch, Camille; Slater, Rebecca; Escobar, Yael Natelie; Smith, John E.; Yang, Lin; Konhilas, John; Lawlor, Michael W.; Ottenheijm, Coen; Granzier, Henk L.

2015-01-01

Nebulin is a giant filamentous protein that is coextensive with the actin filaments of the skeletal muscle sarcomere. Nebulin mutations are the main cause of nemaline myopathy (NEM), with typical adult patients having low expression of nebulin, yet the roles of nebulin in adult muscle remain poorly understood. To establish nebulin's functional roles in adult muscle, we studied a novel conditional nebulin KO (Neb cKO) mouse model in which nebulin deletion was driven by the muscle creatine kinase (MCK) promotor. Neb cKO mice are born with high nebulin levels in their skeletal muscles, but within weeks after birth nebulin expression rapidly falls to barely detectable levels Surprisingly, a large fraction of the mice survive to adulthood with low nebulin levels (<5% of control), contain nemaline rods and undergo fiber-type switching toward oxidative types. Nebulin deficiency causes a large deficit in specific force, and mechanistic studies provide evidence that a reduced fraction of force-generating cross-bridges and shortened thin filaments contribute to the force deficit. Muscles rich in glycolytic fibers upregulate proteolysis pathways (MuRF-1, Fbxo30/MUSA1, Gadd45a) and undergo hypotrophy with smaller cross-sectional areas (CSAs), worsening their force deficit. Muscles rich in oxidative fibers do not have smaller weights and can even have hypertrophy, offsetting their specific-force deficit. These studies reveal nebulin as critically important for force development and trophicity in adult muscle. The Neb cKO phenocopies important aspects of NEM (muscle weakness, oxidative fiber-type predominance, variable trophicity effects, nemaline rods) and will be highly useful to test therapeutic approaches to ameliorate muscle weakness. PMID:26123491

Human primary myoblast cell cultures from non-diabetic insulin resistant subjects retain defects in insulin action.

PubMed Central

Thompson, D B; Pratley, R; Ossowski, V

1996-01-01

Insulin resistance is a predictor of the development of noninsulin-dependent diabetes mellitus (NIDDM) in humans. It is unclear whether insulin resistance is a primary defect leading to NIDDM or the result of hyperinsulinemia and hyperglycemia. To determine if insulin resistance is the result of extrinsic factors such as hyperinsulinemia primary skeletal muscle cell cultures were established from muscle biopsies from Pima Indians with differing in vivo insulin sensitivities. These cell cultures expressed a variety of muscle-specific phenotypes including the proteins alpha-actinin and myosin, muscle-specific creatine kinase activity, and RNA encoding GLUT4, MYF5, MYOD1, and MYOGENIN. Labeled glucose was used to measure the insulin-stimulated conversion of glucose to glycogen in these cultures. The in vivo rates of insulin-stimulated glycogen production (insulin resistance) were correlated with in vitro measures of glycogen production (P = 0.007, r = 0.58). This defect in insulin action is stable in a uniform culture environment and is retained over time. The retention of insulin resistance in myoblast derived cell cultures is consistent with the expression of an underlying biochemical defect in insulin resistant skeletal muscle. PMID:8941652

Dietary protein intake may reduce hospitalisation due to infection in Māori of advanced age: LiLACS NZ.

PubMed

Wham, Carol; Baggett, Fiona; Teh, Ruth; Moyes, Simon; Kēpa, Mere; Connolly, Martin; Jatrana, Santosh; Kerse, Ngaire

2015-08-01

To investigate factors related to hospital admission for infection, specifically examining nutrient intakes of Māori in advanced age (80+ years). Face-to-face interviews with 200 Māori (85 men) to obtain demographic, social and health information. Diagnoses were validated against medical records. Detailed nutritional assessment using the 24-hour multiple-pass recall method was collected on two separate days. FOODfiles was used to analyse nutrient intake. National Health Index (NHI) numbers were matched to hospitalisations over a two-year period (12 months prior and 12 months following dietary assessment). Selected International Classification of Disease (ICD) codes were used to identify admissions related to infection. A total of 18% of participants were hospitalised due to infection, most commonly lower respiratory tract infection. Controlling for age, gender, NZ deprivation index, diabetes, CVD and chronic lung disease, a lower energy-adjusted protein intake was independently associated with hospitalisation due to infection: OR (95%CI) 1.14 (1.00-1.29), p=0.046. Protein intake may have a protective effect on the nutrition-related morbidity of older Māori. Improving dietary protein intake is a simple strategy for dietary modification aiming to decrease the risk of infections that lead to hospitalisation and other morbidities. © 2015 Public Health Association of Australia.

Narratives and traits in personality development among New Zealand Māori, Chinese, and European adolescents.

PubMed

Reese, Elaine; Chen, Yan; McAnally, Helena M; Myftari, Ella; Neha, Tia; Wang, Qi; Jack, Fiona

2014-07-01

Narrative and trait levels of personality were assessed in a sample of 268 adolescents from age 12 to 21 from New Zealand Māori, Chinese, and European cultures. Adolescents narrated three critical events and completed a Big Five personality inventory. Each narrative was coded for causal and thematic coherence. NZ Chinese adolescents reported lower levels of extraversion, agreeableness, conscientiousness, and openness, and higher levels of neuroticism, than NZ Māori or European adolescents. Cultural differences were also evident in narrative coherence. Adolescents in all three groups demonstrated age-related increases in thematic coherence, but only NZ European adolescents demonstrated the expected age-related increases in causal coherence. Narrative identity and traits were distinct aspects of personality for younger adolescents, but were linked for middle and older adolescents. These findings support the importance of both narrative identity and traits in understanding personality development in adolescents across cultures. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

[Reconstruction of facial soft tissue defects with pedicled expanded flaps].

PubMed

Yangqun, Li; Yong, Tang; Wen, Chen; Zhe, Yang; Muxin, Zhao; Lisi, Xu; Chunmei, Hu; Yuanyuan, Liu; Ning, Ma; Jun, Feng; Weixin, Wang

2014-09-01

To investigate the application of pedicled expanded flaps for the reconstruction of facial soft tissue defects. The expanded skin flaps, pedicled with orbicularis oculi muscle, submental artery, the branch of facial artery, superficial temporal artery, interior upper arm artery, had similar texture and color as facial soft tissue. The pedicled expanded flaps have repaired the facial soft tissue defects. Between Jan. 2003 to Dec. 2013, 157 cases with facial soft tissue defects were reconstructed by pedicled expanded flaps. Epidermal necrosis happened at the distal end of 8 expanded flaps, pedicled with interior upper arm artery(4 cases), orbicularis oculi muscle(3 cases) and submental artery(1 case), which healed spontaneously after dressing. All the other flaps survived completely with similar color and inconspicuous scar. 112 cases were followed up for 8 months to 8 years. Satisfactory results were achieved in 75 cases. 37 cases with hypertrophic scar at incisions need secondary operation. Island pedicled expanded flap with similar texture and color as facial soft tissue is suitable for facial soft tissue defects. The facial extra-incision and large dog-ear deformity could be avoided.

The ALMA early science view of FUor/EXor objects - IV. Misaligned outflows in the complex star-forming environment of V1647 Ori and McNeil's Nebula

NASA Astrophysics Data System (ADS)

Principe, David A.; Cieza, Lucas; Hales, Antonio; Zurlo, Alice; Williams, Jonathan; Ruíz-Rodríguez, Dary; Canovas, Hector; Casassus, Simon; Mužić, Koraljka; Perez, Sebastian; Tobin, John J.; Zhu, Zhaohuan

2018-01-01

We present Atacama Large Millimeter/sub-millimeter Array (ALMA) observations of the star-forming environment surrounding V1647 Ori, an outbursting FUor/EXor pre-main sequence star. Dust continuum and the (J = 2 - 1) 12CO, 13CO, C18O molecular emission lines were observed to characterize the V1647 Ori circumstellar disc and any large scale molecular features present. We detect continuum emission from the circumstellar disc and determine a radius r = 40 au, inclination i = 17°+6-9 and total disc mass of Mdisc of ∼0.1 M⊙. We do not identify any disc structures associated with nearby companions, massive planets or fragmentation. The molecular cloud environment surrounding V1647 Ori is both structured and complex. We confirm the presence of an excavated cavity north of V1647 Ori and have identified dense material at the base of the optical reflection nebula (McNeil's Nebula) that is actively shaping its surrounding environment. Two distinct outflows have been detected with dynamical ages of ∼11 700 and 17 200 yr. These outflows are misaligned suggesting disc precession over ∼5500 yr as a result of anisotropic accretion events is responsible. The collimated outflows exhibit velocities of ∼2 km s-1, similar in velocity to that of other FUor objects presented in this series, but significantly slower than previous observations and model predictions. The V1647 Ori system is seemingly connected by an 'arm' of material to a large unresolved structure located ∼20 arcsec to the west. The complex environment surrounding V1647 Ori suggests it is in the early stages of star formation, which may relate to its classification as both a FUor and EXor type object.

Rejuvenation of the aged muscle stem cell population restores strength to injured aged muscles

PubMed Central

Cosgrove, Benjamin D.; Gilbert, Penney M.; Porpiglia, Ermelinda; Mourkioti, Foteini; Lee, Steven P.; Corbel, Stephane Y.; Llewellyn, Michael E.; Delp, Scott L.; Blau, Helen M.

2014-01-01

The aged suffer from progressive muscle weakness and regenerative failure. We demonstrate that muscle regeneration is impaired with aging due in part to a cell-autonomous functional decline in skeletal muscle stem cells (MuSCs). Two-thirds of aged MuSCs are intrinsically defective relative to young MuSCs, with reduced capacity to repair myofibers and repopulate the stem cell reservoir in vivo following transplantation due to a higher incidence of cells that express senescence markers and that have elevated p38α/β MAPK activity. We show that these limitations cannot be overcome by transplantation into the microenvironment of young recipient muscles. In contrast, subjecting the aged MuSC population to transient inhibition of p38α/β in conjunction with culture on soft hydrogel substrates rapidly expands the residual functional aged MuSC population, rejuvenating its potential for regeneration, serial transplantation, and strengthening damaged muscles of aged mice. These findings reveal a synergy between biophysical and biochemical cues that provides a paradigm for a localized autologous muscle stem cell therapy in aged individuals. PMID:24531378

Ghrelin knockout mice display defective skeletal muscle regeneration and impaired satellite cell self-renewal.

PubMed

Angelino, Elia; Reano, Simone; Bollo, Alessandro; Ferrara, Michele; De Feudis, Marilisa; Sustova, Hana; Agosti, Emanuela; Clerici, Sara; Prodam, Flavia; Tomasetto, Catherine-Laure; Graziani, Andrea; Filigheddu, Nicoletta

2018-05-30

Muscle regeneration depends on satellite cells (SCs), quiescent precursors that, in consequence of injury or pathological states such as muscular dystrophies, activate, proliferate, and differentiate to repair the damaged tissue. A subset of SCs undergoes self-renewal, thus preserving the SC pool and its regenerative potential. The peptides produced by the ghrelin gene, i.e., acylated ghrelin (AG), unacylated ghrelin (UnAG), and obestatin (Ob), affect skeletal muscle biology in several ways, not always with overlapping effects. In particular, UnAG and Ob promote SC self-renewal and myoblast differentiation, thus fostering muscle regeneration. To delineate the endogenous contribution of preproghrelin in muscle regeneration, we evaluated the repair process in Ghrl -/- mice upon CTX-induced injury. Although muscles from Ghrl -/- mice do not visibly differ from WT muscles in term of weight, structure, and SCs content, muscle regeneration after CTX-induced injury is impaired in Ghrl -/- mice, indicating that ghrelin-derived peptides actively participate in muscle repair. Remarkably, the lack of ghrelin gene impacts SC self-renewal during regeneration. Although we cannot discern the specific Ghrl-derived peptide responsible for such activities, these data indicate that Ghrl contributes to a proper muscle regeneration.

Mob/oriT, a mobilizable site-specific recombination system for unmarked genetic manipulation in Bacillus thuringiensis and Bacillus cereus.

PubMed

Wang, Pengxia; Zhu, Yiguang; Zhang, Yuyang; Zhang, Chunyi; Xu, Jianyi; Deng, Yun; Peng, Donghai; Ruan, Lifang; Sun, Ming

2016-06-10

Bacillus thuringiensis and Bacillus cereus are two important species in B. cereus group. The intensive study of these strains at the molecular level and construction of genetically modified bacteria requires the development of efficient genetic tools. To insert genes into or delete genes from bacterial chromosomes, marker-less manipulation methods were employed. We present a novel genetic manipulation method for B. thuringiensis and B. cereus strains that does not leave selection markers. Our approach takes advantage of the relaxase Mob02281 encoded by plasmid pBMB0228 from Bacillus thuringiensis. In addition to its mobilization function, this Mob protein can mediate recombination between oriT sites. The Mob02281 mobilization module was associated with a spectinomycin-resistance gene to form a Mob-Spc cassette, which was flanked by the core 24-bp oriT sequences from pBMB0228. A strain in which the wild-type chromosome was replaced with the modified copy containing the Mob-Spc cassette at the target locus was obtained via homologous recombination. Thus, the spectinomycin-resistance gene can be used to screen for Mob-Spc cassette integration mutants. Recombination between the two oriT sequences mediated by Mob02281, encoded by the Mob-Spc cassette, resulted in the excision of the Mob-Spc cassette, producing the desired chromosomal alteration without introducing unwanted selection markers. We used this system to generate an in-frame deletion of a target gene in B. thuringiensis as well as a gene located in an operon of B. cereus. Moreover, we demonstrated that this system can be used to introduce a single gene or an expression cassette of interest in B. thuringiensis. The Mob/oriT recombination system provides an efficient method for unmarked genetic manipulation and for constructing genetically modified bacteria of B. thuringiensis and B. cereus. Our method extends the available genetic tools for B. thuringiensis and B. cereus strains.

PHRED-1 is a divergent neurexin-1 homolog that organizes muscle fibers and patterns organs during regeneration.

PubMed

Adler, Carolyn E; Sánchez Alvarado, Alejandro

2017-07-01

Regeneration of body parts requires the replacement of multiple cell types. To dissect this complex process, we utilized planarian flatworms that are capable of regenerating any tissue after amputation. An RNAi screen for genes involved in regeneration of the pharynx identified a novel gene, Pharynx regeneration defective-1 (PHRED-1) as essential for normal pharynx regeneration. PHRED-1 is a predicted transmembrane protein containing EGF, Laminin G, and WD40 domains, is expressed in muscle, and has predicted homologs restricted to other lophotrochozoan species. Knockdown of PHRED-1 causes abnormal regeneration of muscle fibers in both the pharynx and body wall muscle. In addition to defects in muscle regeneration, knockdown of PHRED-1 or the bHLH transcription factor MyoD also causes defects in muscle and intestinal regeneration. Together, our data demonstrate that muscle plays a key role in restoring the structural integrity of closely associated organs, and in planarians it may form a scaffold that facilitates normal intestinal branching. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Do community-dwelling Māori and Pacific peoples present with dementia at a younger age and at a later stage compared with NZ Europeans?

PubMed

Cullum, Sarah; Mullin, Katherine; Zeng, Irene; Yates, Susan; Payman, Vahid; Fisher, Mark; Cheung, Gary

2018-05-15

Ethnicity may affect presentation to clinical services in people with dementia; however, no studies have examined this in Māori or Pacific peoples in New Zealand (NZ). Our objective was to examine the routinely collected clinical data from a memory assessment service in South Auckland to examine the presentation of dementia in the major NZ ethnic groups. A total of 360 patients presenting to a memory service with a new diagnosis of dementia were included in this study. Demographic data (age, sex, and ethnicity) and dementia sub-type and severity were analyzed. There were 142 NZ European (mean age: 79.2, SD 7.4), 43 Māori (mean age: 70.2, SD 7.6), 126 Pacific (mean age: 74.3, SD 7.6), and 49 other ethnicities (mean age: 78.0, SD 8.5) presenting with a new diagnosis of dementia. After adjustment for gender and dementia subtype, Māori and Pacific patients were 8.5 and 5.3 years younger than NZ European patients (P < 0.0001). Pacific peoples tended to present with more advanced dementia (OR = 1.63, 95% CI: 0.98-2.70, P = 0.06) after adjustment for age and gender. There was little difference in the subtypes of dementia between ethnic groups. Māori and Pacific peoples with dementia presented to an NZ memory service at a younger age than NZ Europeans, and Pacific peoples presented with more advanced dementia. A population-based epidemiological study is critical to determine whether Māori and Pacific peoples have indeed a higher risk of developing dementia at a younger age. Copyright © 2018 John Wiley & Sons, Ltd.

Optimization of Soft Tissue Management, Spacer Design, and Grafting Strategies for Large Segmental Bone Defects using the Chronic Caprine Tibial Defect Model

DTIC Science & Technology

2016-12-01

gastrocnemius muscles. 4. Place an interlocking intramedullary nail using a custom spacer to maintain 5-cm defect length. 5. Place a pre-molded 5 cm long x...2 cm diameter PMMA spacer around the nail in the defect. 6. Irrigate the wound with normal (0.9 %) saline and close the wound. The Treatment...PMMA spacer using a “bomb bay door opening”. 4. Remove the spacer without damaging the membrane or nail . 5. Collect appropriate IM samples as

Muscle-Bone Interactions in Pediatric Bone Diseases.

PubMed

Veilleux, Louis-Nicolas; Rauch, Frank

2017-10-01

Here, we review the skeletal effects of pediatric muscle disorders as well as muscle impairment in pediatric bone disorders. When starting in utero, muscle disorders can lead to congenital multiple contractures. Pediatric-onset muscle weakness such as cerebral palsy, Duchenne muscular dystrophy, spinal muscular atrophy, or spina bifida typically are associated with small diameter of long-bone shafts, low density of metaphyseal bone, and increased fracture incidence in the lower extremities, in particular, the distal femur. Primary bone diseases can affect muscles through generic mechanisms, such as decreased physical activity or in disease-specific ways. For example, the collagen defect underlying the bone fragility of osteogenesis imperfecta may also affect muscle force generation or transmission. Transforming growth factor beta released from bone in Camurati Engelman disease may decrease muscle function. Considering muscle-bone interactions does not only contribute to the understanding of musculoskeletal disorders but also can identify new targets for therapeutic interventions.

Functional reconstruction of complex tendo Achilles defect by free latissimus dorsi muscle flap

PubMed Central

Upadhyaya, Divya N.; Khanna, Vaibhav; Kohli, Romesh; Tulsi, Satendar P. S.; Garg, Sandeep

2012-01-01

Managing the complex tendo Achilles defect involves reconstructing the Achilles tendon as well as providing soft tissue cover to the heel area. The advent of microsurgery has revolutionised the reconstruction of this difficult defect providing a number of options to the reconstructive surgeon. We present a case of complex tendo Achilles defect reconstructed by the latissimus dorsi free flap. PMID:23450740

A tertiary approach to improving equity in health: quantitative analysis of the Māori and Pacific Admission Scheme (MAPAS) process, 2008-2012.

PubMed

Curtis, Elana; Wikaire, Erena; Jiang, Yannan; McMillan, Louise; Loto, Rob; Airini; Reid, Papaarangi

2015-01-20

Achieving health equity for indigenous and ethnic minority populations requires the development of an ethnically diverse health workforce. This study explores a tertiary admission programme targeting Māori and Pacific applicants to nursing, pharmacy and health sciences (a precursor to medicine) at the University of Auckland (UoA), Aotearoa New Zealand (NZ). Application of cognitive and non-cognitive selection tools, including a Multiple Mini Interview (MMI), are examined. Indigenous Kaupapa Māori methodology guided analysis of the Māori and Pacific Admission Scheme (MAPAS) for the years 2008-2012. Multiple logistic regression models were used to identify the predicted effect of admission variables on the final MAPAS recommendation of best starting point for success in health professional study i.e. 'CertHSc' (Certificate in Health Sciences, bridging/foundation), 'Bachelor' (degree-level) or 'Not FMHS' (Faculty of Medical and Health Sciences). Regression analyses controlled for interview year, gender and ancestry. Of the 918 MAPAS interviewees: 35% (319) were Māori, 58% (530) Pacific, 7% (68) Māori/Pacific; 71% (653) school leavers; 72% (662) females. The average rank score was 167/320, 40-80 credits below guaranteed FMHS degree offers. Just under half of all interviewees were recommended 'CertHSc' 47% (428), 13% (117) 'Bachelor' and 38% (332) 'Not FMHS' as the best starting point. Strong associations were identified between Bachelor recommendation and exposure to Any 2 Sciences (OR:7.897, CI:3.855-16.175; p < 0.0001), higher rank score (OR:1.043, CI:1.034-1.052; p < 0.0001) and higher scores on MAPAS mathematics test (OR:1.043, CI:1.028-1.059; p < 0.0001). MMI stations had mixed associations, with academic preparation and career aspirations more consistently associated with recommendations. Our findings raise concerns about the ability of the secondary education sector to prepare Māori and Pacific students adequately for health professional study

Isolation and characterization of mesoangioblasts from facioscapulohumeral muscular dystrophy muscle biopsies.

PubMed

Morosetti, Roberta; Mirabella, Massimiliano; Gliubizzi, Carla; Broccolini, Aldobrando; Sancricca, Cristina; Pescatori, Mario; Gidaro, Teresa; Tasca, Giorgio; Frusciante, Roberto; Tonali, Pietro Attilio; Cossu, Giulio; Ricci, Enzo

2007-12-01

Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent inherited muscle disease. Because in FSHD patients the coexistence of affected and unaffected muscles is common, myoblasts expanded from unaffected FSHD muscles have been proposed as suitable tools for autologous cell transplantation. Mesoangioblasts are a new class of adult stem cells of mesodermal origin, potentially useful for the treatment of primitive myopathies of different etiology. Here, we report the isolation and characterization of mesoangioblasts from FSHD muscle biopsies and describe morphology, proliferation, and differentiation abilities of both mesoangioblasts and myoblasts derived from various affected and unaffected muscles of nine representative FSHD patients. We demonstrate that mesoangioblasts can be efficiently isolated from FSHD muscle biopsies and expanded to an amount of cells necessary to transplant into an adult patient. Proliferating mesoangioblasts from all muscles examined did not differ from controls in terms of morphology, phenotype, proliferation rate, or clonogenicity. However, their differentiation ability into skeletal muscle was variably impaired, and this defect correlated with the overall disease severity and the degree of histopathologic abnormalities of the muscle of origin. A remarkable differentiation defect was observed in mesoangioblasts from all mildly to severely affected FSHD muscles, whereas mesoangioblasts from morphologically normal muscles showed no myogenic differentiation block. Our study could open the way to cell therapy for FSHD patients to limit muscle damage in vivo through the use of autologous mesoangioblasts capable of reaching damaged muscles and engrafting into them, without requiring immune suppression or genetic correction in vitro. Disclosure of potential conflicts of interest is found at the end of this article.

Implantation of In Vitro Tissue Engineered Muscle Repair Constructs and Bladder Acellular Matrices Partially Restore In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss Injury

PubMed Central

Corona, Benjamin T.; Ward, Catherine L.; Baker, Hannah B.; Walters, Thomas J.

2014-01-01

The frank loss of a large volume of skeletal muscle (i.e., volumetric muscle loss [VML]) can lead to functional debilitation and presents a significant problem to civilian and military medicine. Current clinical treatment for VML involves the use of free muscle flaps and physical rehabilitation; however, neither are effective in promoting regeneration of skeletal muscle to replace the tissue that was lost. Toward this end, skeletal muscle tissue engineering therapies have recently shown great promise in offering an unprecedented treatment option for VML. In the current study, we further extend our recent progress (Machingal et al., 2011, Tissue Eng; Corona et al., 2012, Tissue Eng) in the development of tissue engineered muscle repair (TEMR) constructs (i.e., muscle-derived cells [MDCs] seeded on a bladder acellular matrix (BAM) preconditioned with uniaxial mechanical strain) for the treatment of VML. TEMR constructs were implanted into a VML defect in a tibialis anterior (TA) muscle of Lewis rats and observed up to 12 weeks postinjury. The salient findings of the study were (1) TEMR constructs exhibited a highly variable capacity to restore in vivo function of injured TA muscles, wherein TEMR-positive responders (n=6) promoted an ≈61% improvement, but negative responders (n=7) resulted in no improvement compared to nonrepaired controls, (2) TEMR-positive and -negative responders exhibited differential immune responses that may underlie these variant responses, (3) BAM scaffolds (n=7) without cells promoted an ≈26% functional improvement compared to uninjured muscles, (4) TEMR-positive responders promoted muscle fiber regeneration within the initial defect area, while BAM scaffolds did so only sparingly. These findings indicate that TEMR constructs can improve the in vivo functional capacity of the injured musculature at least, in part, by promoting generation of functional skeletal muscle fibers. In short, the degree of functional recovery observed following

PA12 Is digital storytelling ka pai for new zealand māori? using digital storytelling as a method to explore whānau end of life caregiving experiences: a pilot study.

PubMed

Williams, Lisa; Moeke-Maxwell, Tess; Kothari, Shuchi; Pearson, Sarina; Gott, Merryn; Black, Stella; Frey, Rosemary; Wharemate, Rawiri; Hansen, Whio

2015-04-01

Māori regard stories as a preferred method for imparting knowledge through waiata (song), moteatea (poetry), kauwhau (moralistic tale), pakiwaitara (story) and purakau (myths). Storytelling is also an expression of tinorangatiratanga (self-determination); Māori have the right to manage their knowledge, which includes embodiment in forms transcending typical western formulations. Digital storytelling is a process by which 'ordinary people' create short autobiographical videos. It has found application in numerous disciplines including public health and has been used to articulatethe experiences of those often excluded from knowledge production. To explore the use of digital storytelling as a research method for learning about whānau (family) experiences providing end of life care for kaumātua (older people). Eight Māori and their nominated co-creators attended a three-day digital story telling workshop led by co-researchers Shuchi Kothari and Sarina Pearson. They were guided in the creation of first-person digital stories about caring for kaumātua. The videos were shared at a group screening, and participants completed questionnaires about the workshop and their videos. A Kaupapa Māori narrative analysis was applied to their stories to gain new perspectives on Māori end of life caregiving practices. (Kaupapa Maori research privileges Maori worldviews and indigenous knowledge systems.) Digital storytelling is an appropriate method as Māori is an oral/aural society. It allows Māori to share their stories with others, thus promoting community support at the end of life, befitting a public health approach. Digital storytelling can be a useful method for Māori to express their experiences providing end of life caregiving. © 2015, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Functional resurfacing of the palm: flap selection based on defect analysis.

PubMed

Engelhardt, T O; Rieger, U M; Schwabegger, A H; Pierer, G

2012-02-01

Extensive defect coverage of the palm and anatomical reconstruction of its unique functional capacity remains difficult. In manual laborers, reconstruction of sensation, range of motion, grip strength but also mechanical stability is required. Sensate musculo-/fasciocutaneous flaps bear disadvantages of tissue mobility with shifting/bulkiness under stress. Thin muscle and fascial flaps show adherence but preclude sensory nerve coaptation. The purpose of this review is to present our algorithm for reliable selection of the most appropriate procedure based on defect analysis. Defect analysis focusing on units of tactile gnosis provides information to weigh needs for sensation or soft tissue stability. We distinguish radial unit (r)-thenar, ulnar unit (u)-hypothenar and unit (c)-central plus distal palm. Individual parameters need similar consideration to choose adequate treatment. Unit (r) and unit (u) are regions of secondary touch demanding protective sensation. Restoration of sensation using neurovascular, fasciocutaneous flaps is recommended. In unit (c), tactile gnosis is of less, mechanical resistance of greater value. Reconstruction of soft tissue resistance is suggested first in this unit. In laborers, free fascial- or muscle flaps with plantar instep skin grafts may achieve near to anatomical reconstruction with minimal sensation. Combined defects involving unit (c) require correlation with individual parameters for optimal flap selection. Defect coverage of the palm should not consist of merely providing sensate vascularized tissue. The most appropriate procedure should be derived from careful defect analysis to achieve near to anatomical reconstruction. In laborers, defect related demands need close correlation with sensation and mechanical stability to be expected. Copyright © 2011 Wiley Periodicals, Inc.

A novel perspective for burn-induced myopathy: Membrane repair defect

PubMed Central

Wang, Chao; Wang, Hongyu; Wu, Dan; Hu, Jianhong; Wu, Wei; Zhang, Yong; Peng, Xi

2016-01-01

Myopathy is a common complication of severe burn patients. One potential cause of this myopathy could be failure of the plasma membrane to undergo repair following injuries generated from toxin or exercise. The aim of this study is to assess systemic effect on muscle membrane repair deficiency in burn injury. Skeletal muscle fibers isolated from burn-injured mice were damaged with a UV laser and dye influx imaged confocally to evaluate membrane repair capacity. Membrane repair failure was also tested in burn-injured mice subjected to myotoxin or treadmill exercise. We further used C2C12 myotubules and animal models to investigate the role of MG53 in development of burn-induced membrane repair defect. We demonstrated that skeletal muscle myofibers in burn-injured mice showed significantly more dye uptake after laser damage than controls, indicating a membrane repair deficiency. Myotoxin or treadmill exercise also resulted in a higher-grade repair defect in burn-injured mice. Furthermore, we observed that burn injury induced a significant decrease in MG53 levels and its dimerization in skeletal muscles. Our findings highlight a new mechanism that implicates membrane repair failure as an underlying cause of burn-induced myopathy. And, the disorders in MG53 expression and MG53 dimerization are involved in this cellular pathology. PMID:27545095

Phosphatidylinositol 3-kinase inhibition restores Ca2+ release defects and prolongs survival in myotubularin-deficient mice

PubMed Central

Kutchukian, Candice; Lo Scrudato, Mirella; Tourneur, Yves; Poulard, Karine; Vignaud, Alban; Berthier, Christine; Allard, Bruno; Lawlor, Michael W.; Buj-Bello, Ana; Jacquemond, Vincent

2016-01-01

Mutations in the gene encoding the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for a pediatric disease of skeletal muscle named myotubular myopathy (XLMTM). Muscle fibers from MTM1-deficient mice present defects in excitation–contraction (EC) coupling likely responsible for the disease-associated fatal muscle weakness. However, the mechanism leading to EC coupling failure remains unclear. During normal skeletal muscle EC coupling, transverse (t) tubule depolarization triggers sarcoplasmic reticulum (SR) Ca2+ release through ryanodine receptor channels gated by conformational coupling with the t-tubule voltage-sensing dihydropyridine receptors. We report that MTM1 deficiency is associated with a 60% depression of global SR Ca2+ release over the full range of voltage sensitivity of EC coupling. SR Ca2+ release in the diseased fibers is also slower than in normal fibers, or delayed following voltage activation, consistent with the contribution of Ca2+-gated ryanodine receptors to EC coupling. In addition, we found that SR Ca2+ release is spatially heterogeneous within myotubularin-deficient muscle fibers, with focally defective areas recapitulating the global alterations. Importantly, we found that pharmacological inhibition of phosphatidylinositol 3-kinase (PtdIns 3-kinase) activity rescues the Ca2+ release defects in isolated muscle fibers and increases the lifespan and mobility of XLMTM mice, providing proof of concept for the use of PtdIns 3-kinase inhibitors in myotubular myopathy and suggesting that unbalanced PtdIns 3-kinase activity plays a critical role in the pathological process. PMID:27911767

On the origin, homologies and evolution of primate facial muscles, with a particular focus on hominoids and a suggested unifying nomenclature for the facial muscles of the Mammalia

PubMed Central

Diogo, R; Wood, B A; Aziz, M A; Burrows, A

2009-01-01

The mammalian facial muscles are a subgroup of hyoid muscles (i.e. muscles innervated by cranial nerve VII). They are usually attached to freely movable skin and are responsible for facial expressions. In this study we provide an account of the origin, homologies and evolution of the primate facial muscles, based on dissections of various primate and non-primate taxa and a review of the literature. We provide data not previously reported, including photographs showing in detail the facial muscles of primates such as gibbons and orangutans. We show that the facial muscles usually present in strepsirhines are basically the same muscles that are present in non-primate mammals such as tree-shrews. The exceptions are that strepsirhines often have a muscle that is usually not differentiated in tree-shrews, the depressor supercilii, and lack two muscles that are usually differentiated in these mammals, the zygomatico-orbicularis and sphincter colli superficialis. Monkeys such as macaques usually lack two muscles that are often present in strepsirhines, the sphincter colli profundus and mandibulo-auricularis, but have some muscles that are usually absent as distinct structures in non-anthropoid primates, e.g. the levator labii superioris alaeque nasi, levator labii superioris, nasalis, depressor septi nasi, depressor anguli oris and depressor labii inferioris. In turn, macaques typically lack a risorius, auricularis anterior and temporoparietalis, which are found in hominoids such as humans, but have muscles that are usually not differentiated in members of some hominoid taxa, e.g. the platysma cervicale (usually not differentiated in orangutans, panins and humans) and auricularis posterior (usually not differentiated in orangutans). Based on our observations, comparisons and review of the literature, we propose a unifying, coherent nomenclature for the facial muscles of the Mammalia as a whole and provide a list of more than 300 synonyms that have been used in the

THE RADIO JET ASSOCIATED WITH THE MULTIPLE V380 ORI SYSTEM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodríguez, Luis F.; Yam, J. Omar; Carrasco-González, Carlos

The giant Herbig–Haro object 222 extends over ∼6′ in the plane of the sky, with a bow shock morphology. The identification of its exciting source has remained uncertain over the years. A non-thermal radio source located at the core of the shock structure was proposed to be the exciting source. However, Very Large Array studies showed that the radio source has a clear morphology of radio galaxy and a lack of flux variations or proper motions, favoring an extragalactic origin. Recently, an optical–IR study proposed that this giant HH object is driven by the multiple stellar system V380 Ori, locatedmore » about 23′ to the SE of HH 222. The exciting sources of HH systems are usually detected as weak free–free emitters at centimeter wavelengths. Here, we report the detection of an elongated radio source associated with the Herbig Be star or with its close infrared companion in the multiple V380 Ori system. This radio source has the characteristics of a thermal radio jet and is aligned with the direction of the giant outflow defined by HH 222 and its suggested counterpart to the SE, HH 1041. We propose that this radio jet traces the origin of the large scale HH outflow. Assuming that the jet arises from the Herbig Be star, the radio luminosity is a few times smaller than the value expected from the radio–bolometric correlation for radio jets, confirming that this is a more evolved object than those used to establish the correlation.« less

Muscle Mitochondrial Uncoupling Dismantles Neuromuscular Junction and Triggers Distal Degeneration of Motor Neurons

PubMed Central

Dupuis, Luc; Gonzalez de Aguilar, Jose-Luis; Echaniz-Laguna, Andoni; Eschbach, Judith; Rene, Frédérique; Oudart, Hugues; Halter, Benoit; Huze, Caroline; Schaeffer, Laurent; Bouillaud, Frédéric; Loeffler, Jean-Philippe

2009-01-01

Background Amyotrophic lateral sclerosis (ALS), the most frequent adult onset motor neuron disease, is associated with hypermetabolism linked to defects in muscle mitochondrial energy metabolism such as ATP depletion and increased oxygen consumption. It remains unknown whether muscle abnormalities in energy metabolism are causally involved in the destruction of neuromuscular junction (NMJ) and subsequent motor neuron degeneration during ALS. Methodology/Principal Findings We studied transgenic mice with muscular overexpression of uncoupling protein 1 (UCP1), a potent mitochondrial uncoupler, as a model of muscle restricted hypermetabolism. These animals displayed age-dependent deterioration of the NMJ that correlated with progressive signs of denervation and a mild late-onset motor neuron pathology. NMJ regeneration and functional recovery were profoundly delayed following injury of the sciatic nerve and muscle mitochondrial uncoupling exacerbated the pathology of an ALS animal model. Conclusions/Significance These findings provide the proof of principle that a muscle restricted mitochondrial defect is sufficient to generate motor neuron degeneration and suggest that therapeutic strategies targeted at muscle metabolism might prove useful for motor neuron diseases. PMID:19404401

HH 222: A GIANT HERBIG-HARO FLOW FROM THE QUADRUPLE SYSTEM V380 ORI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reipurth, Bo; Aspin, Colin; Connelley, M. S.

2013-11-01

HH 222 is a giant shocked region in the L1641 cloud, and is popularly known as the Orion Streamers or ''the waterfall'' on account of its unusual structure. At the center of these streamers are two infrared sources coincident with a nonthermal radio jet aligned along the principal streamer. The unique morphology of HH 222 has long been associated with this radio jet. However, new infrared images show that the two sources are distant elliptical galaxies, indicating that the radio jet is merely an improbable line-of-sight coincidence. Accurate proper motion measurements of HH 222 reveal that the shock structure ismore » a giant bow shock moving directly away from the well-known, very young, Herbig Be star V380 Ori. The already known Herbig-Haro object HH 35 forms part of this flow. A new Herbig-Haro object, HH 1041, is found precisely in the opposite direction of HH 222 and is likely to form part of a counterflow. The total projected extent of this HH complex is 5.3 pc, making it among the largest HH flows known. A second outflow episode from V380 Ori is identified as a pair of HH objects, HH 1031 to the northwest and the already known HH 130 to the southeast, along an axis that deviates from that of HH 222/HH 1041 by only 3.°7. V380 Ori is a hierarchical quadruple system, including a faint companion of spectral type M5 or M6, which at an age of ∼1 Myr corresponds to an object straddling the stellar-to-brown dwarf boundary. We suggest that the HH 222 giant bow shock is a direct result of the dynamical interactions that led to the conversion from an initial non-hierarchical multiple system into a hierarchical configuration. This event occurred no more than 28,000 yr ago, as derived from the proper motions of the HH 222 giant bow shock.« less

Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy

PubMed Central

Risson, Valérie; Mazelin, Laetitia; Roceri, Mila; Sanchez, Hervé; Moncollin, Vincent; Corneloup, Claudine; Richard-Bulteau, Hélène; Vignaud, Alban; Baas, Dominique; Defour, Aurélia; Freyssenet, Damien; Tanti, Jean-François; Le-Marchand-Brustel, Yannick; Ferrier, Bernard; Conjard-Duplany, Agnès; Romanino, Klaas; Bauché, Stéphanie; Hantaï, Daniel; Mueller, Matthias; Kozma, Sara C.; Thomas, George; Rüegg, Markus A.; Ferry, Arnaud; Pende, Mario; Bigard, Xavier; Koulmann, Nathalie

2009-01-01

Mammalian target of rapamycin (mTOR) is a key regulator of cell growth that associates with raptor and rictor to form the mTOR complex 1 (mTORC1) and mTORC2, respectively. Raptor is required for oxidative muscle integrity, whereas rictor is dispensable. In this study, we show that muscle-specific inactivation of mTOR leads to severe myopathy, resulting in premature death. mTOR-deficient muscles display metabolic changes similar to those observed in muscles lacking raptor, including impaired oxidative metabolism, altered mitochondrial regulation, and glycogen accumulation associated with protein kinase B/Akt hyperactivation. In addition, mTOR-deficient muscles exhibit increased basal glucose uptake, whereas whole body glucose homeostasis is essentially maintained. Importantly, loss of mTOR exacerbates the myopathic features in both slow oxidative and fast glycolytic muscles. Moreover, mTOR but not raptor and rictor deficiency leads to reduced muscle dystrophin content. We provide evidence that mTOR controls dystrophin transcription in a cell-autonomous, rapamycin-resistant, and kinase-independent manner. Collectively, our results demonstrate that mTOR acts mainly via mTORC1, whereas regulation of dystrophin is raptor and rictor independent. PMID:20008564

Dynamic Article: Tandem Robotic Technique of Extralevator Abdominoperineal Excision and Rectus Abdominis Muscle Harvest for Immediate Closure of the Pelvic Floor Defect.

PubMed

Singh, Puneet; Teng, Edward; Cannon, Lisa M; Bello, Brian L; Song, David H; Umanskiy, Konstantin

2015-09-01

Extralevator abdominoperineal excision for distal rectal cancers involves cylindrical excision of the mesorectum with wide division of the levator ani muscles. Although this technique has been shown to decrease local cancer recurrence and improve survival, it leaves the patient with a considerable pelvic floor defect that may require reconstruction. We developed an innovative technique of robotic extralevator abdominoperineal excision combined with robotic harvest of the rectus abdominis muscle flap for immediate reconstruction of the pelvic floor defect. This was a retrospective review pilot study. This study was conducted at a tertiary care cancer center. Three patients who underwent robotic extralevator abdominoperineal excision with robotic rectus abdominis flap harvest for distal rectal adenocarcinoma were included. Intraoperative and postoperative outcomes included operative time, intraoperative complications, length of hospital stay, wound complications, incidence of perineal hernia, persistent pain, and functional limitations. Three patients underwent this procedure. The median operative time was 522 minutes with median hospital stay of 6 days. One patient experienced perineal wound complication requiring limited incision and drainage followed by complete healing of the wound by secondary intention. The other 2 patients did not experience any wound complications. Longest follow-up was 16 months. None of the patients developed perineal hernias during this time period. The small sample size and retrospective nature were limitations. This technique confers multiple advantages including improved visualization and dexterity within the pelvis and accurate wide margins at the pelvic floor. An incisionless robotic flap harvest with preservation of the anterior rectus sheath obviates the risk of ventral hernia while providing robust tissue closure of the radiated abdominoperineal excision wound. This technique may result in faster postoperative recovery, decreased

Selective stimulation of facial muscles with a penetrating electrode array in the feline model

PubMed Central

Sahyouni, Ronald; Bhatt, Jay; Djalilian, Hamid R.; Tang, William C.; Middlebrooks, John C.; Lin, Harrison W.

2017-01-01

Objective Permanent facial nerve injury is a difficult challenge for both patients and physicians given its potential for debilitating functional, cosmetic, and psychological sequelae. Although current surgical interventions have provided considerable advancements in facial nerve rehabilitation, they often fail to fully address all impairments. We aim to introduce an alternative approach to facial nerve rehabilitation. Study design Acute experiments in animals with normal facial function. Methods The study included three anesthetized cats. Four facial muscles (levator auris longus, orbicularis oculi, nasalis, and orbicularis oris) were monitored with a standard electromyographic (EMG) facial nerve monitoring system with needle electrodes. The main trunk of the facial nerve was exposed and a 16-channel penetrating electrode array was placed into the nerve. Electrical current pulses were delivered to each stimulating electrode individually. Elicited EMG voltage outputs were recorded for each muscle. Results Stimulation through individual channels selectively activated restricted nerve populations, resulting in selective contraction of individual muscles. Increasing stimulation current levels resulted in increasing EMG voltage responses. Typically, selective activation of two or more distinct muscles was successfully achieved via a single placement of the multi-channel electrode array by selection of appropriate stimulation channels. Conclusion We have established in the animal model the ability of a penetrating electrode array to selectively stimulate restricted fiber populations within the facial nerve and to selectively elicit contractions in specific muscles and regions of the face. These results show promise for the development of a facial nerve implant system. PMID:27312936

Metabolic Disturbance in PCOS: Clinical and Molecular Effects on Skeletal Muscle Tissue

PubMed Central

Silva Dantas, Wagner; Gualano, Bruno; Patrocínio Rocha, Michele; Roberto Grimaldi Barcellos, Cristiano; dos Reis Vieira Yance, Viviane; Miguel Marcondes, José Antonio

2013-01-01

Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise) in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome. PMID:23844380

Metabolic disturbance in PCOS: clinical and molecular effects on skeletal muscle tissue.

PubMed

Dantas, Wagner Silva; Gualano, Bruno; Rocha, Michele Patrocínio; Barcellos, Cristiano Roberto Grimaldi; dos Reis Vieira Yance, Viviane; Marcondes, José Antonio Miguel

2013-01-01

Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise) in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome.

Pathogenicity of exopolysaccharide-producing Actinomyces oris isolated from an apical abscess lesion

PubMed Central

Yamane, K; Nambu, T; Yamanaka, T; Ishihara, K; Tatami, T; Mashimo, C; Walker, C B; Leung, K-P; Fukushima, H

2013-01-01

Aim To demonstrate a capacity for producing exopolysaccharides (EPSs) and an ability to form biofilm on abiotic materials of Actinomyces oris strain K20. Methodology The productivity of EPSs and the ability to form biofilm of strain K20 were evaluated by measuring viscosity of spent culture media and by scanning electron microscopy (SEM) and the biofilm assay on microtitre plates, respectively. High-performance liquid chromatography was used to determine the chemical composition of the viscous materials. To examine the role of the viscous materials attributable to the pathogenicity in this organism, the ability of strain K20 to induce abscess formation was compared in mice to that of ATCC 27044. Results The viscosity of the spent culture media of K20 was significantly higher than that of ATCC 27044. Strain K20 showed dense meshwork structures around the cells and formed biofilms on microtitre plates, whereas ATCC 27044 did not. Chemical analysis of the viscous materials revealed that they were mainly composed of neutral sugars with mannose constituting 77.5% of the polysaccharides. Strain K20 induced persistent abscesses in mice lasting at least 5 days at a concentration of 108 cells mL−1, whereas abscesses induced by ATCC 27044 healed and disappeared or decreased in size at day 5. Conclusions Strain K20 produced EPSs, mainly consisting of mannose, and formed biofilms. This phenotype might play an important role for A. oris to express virulence through the progression of apical periodontitis. PMID:22900599

Pathogenicity of exopolysaccharide-producing Actinomyces oris isolated from an apical abscess lesion.

PubMed

Yamane, K; Nambu, T; Yamanaka, T; Ishihara, K; Tatami, T; Mashimo, C; Walker, C B; Leung, K-P; Fukushima, H

2013-02-01

To demonstrate a capacity for producing exopolysaccharides (EPSs) and an ability to form biofilm on abiotic materials of Actinomyces oris strain K20. The productivity of EPSs and the ability to form biofilm of strain K20 were evaluated by measuring viscosity of spent culture media and by scanning electron microscopy (SEM) and the biofilm assay on microtitre plates, respectively. High-performance liquid chromatography was used to determine the chemical composition of the viscous materials. To examine the role of the viscous materials attributable to the pathogenicity in this organism, the ability of strain K20 to induce abscess formation was compared in mice to that of ATCC 27044. The viscosity of the spent culture media of K20 was significantly higher than that of ATCC 27044. Strain K20 showed dense meshwork structures around the cells and formed biofilms on microtitre plates, whereas ATCC 27044 did not. Chemical analysis of the viscous materials revealed that they were mainly composed of neutral sugars with mannose constituting 77.5% of the polysaccharides. Strain K20 induced persistent abscesses in mice lasting at least 5 days at a concentration of 10(8) cells mL(-1), whereas abscesses induced by ATCC 27044 healed and disappeared or decreased in size at day 5. Strain K20 produced EPSs, mainly consisting of mannose, and formed biofilms. This phenotype might play an important role for A. oris to express virulence through the progression of apical periodontitis. © 2012 International Endodontic Journal.

Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy.

PubMed

Martin, Elizabeth A; Barresi, Rita; Byrne, Barry J; Tsimerinov, Evgeny I; Scott, Bryan L; Walker, Ashley E; Gurudevan, Swaminatha V; Anene, Francine; Elashoff, Robert M; Thomas, Gail D; Victor, Ronald G

2012-11-28

Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin's rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived NO attenuates local α-adrenergic vasoconstriction, thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective-causing functional muscle ischemia-in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. We report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3',5'-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD.

Store-operated Ca(2+) entry (SOCE) contributes to normal skeletal muscle contractility in young but not in aged skeletal muscle.

PubMed

Thornton, Angela M; Zhao, Xiaoli; Weisleder, Noah; Brotto, Leticia S; Bougoin, Sylvain; Nosek, Thomas M; Reid, Michael; Hardin, Brian; Pan, Zui; Ma, Jianjie; Parness, Jerome; Brotto, Marco

2011-06-01

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca(2+) to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca(2+) entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca(2+) to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca(2+) release channel-mediated Ca(2+) release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca(2+) entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle.

Pedicled Temporalis Muscle Flap for Craniofacial Reconstruction: A 35-Year Clinical Experience with 366 Flaps.

PubMed

Spanio di Spilimbergo, Stefano; Nordera, Paolo; Mardini, Samir; Castiglione, Giusy; Chim, Harvey; Pinna, Vittore; Brunello, Massimo; Cusino, Claudio; Roberto, Squaquara; Baciliero, Ugo

2017-02-01

In the past 130 years, the temporalis muscle flap has been used for a variety of different indications. In this age of microsurgery and perforator flaps, the temporalis muscle flap still has many useful applications for craniofacial reconstruction. Three hundred sixty-six temporalis muscle flaps were performed in a single center between 1978 and 2012. The authors divided the cases into two series-before and after 1994-because, after 1994, they started to perform free flap reconstructions, and indications for reconstruction with a temporalis muscle flap were changed RESULTS:: In the series after 1994, flaps were most commonly used for reconstruction of defects in the maxilla, mandible, and oropharynx, in addition to facial reanimation and filling of orbital defects. Complications included total flap necrosis (1.6 percent) and partial flap necrosis (10.7 percent). The rate of material extrusion at the donor site decreased after porous polyethylene was uniformly used for reconstruction from 17.1 to 7.9 percent. The pedicled temporalis muscle flap continues to have many applications in craniofacial reconstruction. With increasing use of free flaps, the authors' indications for the pedicled temporalis muscle flap are now restricted to (1) orbital filling for congenital or acquired anophthalmia; (2) filling of unilateral maxillectomy defects; and (3) facial reanimation in selected cases of facial nerve palsy. Therapeutic, IV.

Abnormal cation transport in uremia. Mechanisms in adipocytes and skeletal muscle from uremic rats.

PubMed

Druml, W; Kelly, R A; May, R C; Mitch, W E

1988-04-01

The cause of the abnormal active cation transport in erythrocytes of some uremic patients is unknown. In isolated adipocytes and skeletal muscle from chronically uremic chronic renal failure rats, basal sodium pump activity was decreased by 36 and 30%, and intracellular sodium was increased by 90 and 50%, respectively, compared with pair-fed control rats; insulin-stimulated sodium pump activity was preserved in both tissues. Lower basal NaK-ATPase activity in adipocytes was due to a proportionate decline in [3H]ouabain binding, while in muscle, [3H]ouabain binding was not changed, indicating that the NaK-ATPase turnover rate was decreased. Normal muscle, but not normal adipocytes, acquired defective Na pump activity when incubated in uremic sera. Thus, the mechanism for defective active cation transport in CRF is multifactorial and tissue specific. Sodium-dependent amino acid transport in adipocytes closely paralleled diminished Na pump activity (r = 0.91), indicating the importance of this defect to abnormal cellular metabolism in uremia.

Abnormal cation transport in uremia. Mechanisms in adipocytes and skeletal muscle from uremic rats.

PubMed Central

Druml, W; Kelly, R A; May, R C; Mitch, W E

1988-01-01

The cause of the abnormal active cation transport in erythrocytes of some uremic patients is unknown. In isolated adipocytes and skeletal muscle from chronically uremic chronic renal failure rats, basal sodium pump activity was decreased by 36 and 30%, and intracellular sodium was increased by 90 and 50%, respectively, compared with pair-fed control rats; insulin-stimulated sodium pump activity was preserved in both tissues. Lower basal NaK-ATPase activity in adipocytes was due to a proportionate decline in [3H]ouabain binding, while in muscle, [3H]ouabain binding was not changed, indicating that the NaK-ATPase turnover rate was decreased. Normal muscle, but not normal adipocytes, acquired defective Na pump activity when incubated in uremic sera. Thus, the mechanism for defective active cation transport in CRF is multifactorial and tissue specific. Sodium-dependent amino acid transport in adipocytes closely paralleled diminished Na pump activity (r = 0.91), indicating the importance of this defect to abnormal cellular metabolism in uremia. PMID:2832446

MeCP2 Affects Skeletal Muscle Growth and Morphology through Non Cell-Autonomous Mechanisms.

PubMed

Conti, Valentina; Gandaglia, Anna; Galli, Francesco; Tirone, Mario; Bellini, Elisa; Campana, Lara; Kilstrup-Nielsen, Charlotte; Rovere-Querini, Patrizia; Brunelli, Silvia; Landsberger, Nicoletta

2015-01-01

Rett syndrome (RTT) is an autism spectrum disorder mainly caused by mutations in the X-linked MECP2 gene and affecting roughly 1 out of 10.000 born girls. Symptoms range in severity and include stereotypical movement, lack of spoken language, seizures, ataxia and severe intellectual disability. Notably, muscle tone is generally abnormal in RTT girls and women and the Mecp2-null mouse model constitutively reflects this disease feature. We hypothesized that MeCP2 in muscle might physiologically contribute to its development and/or homeostasis, and conversely its defects in RTT might alter the tissue integrity or function. We show here that a disorganized architecture, with hypotrophic fibres and tissue fibrosis, characterizes skeletal muscles retrieved from Mecp2-null mice. Alterations of the IGF-1/Akt/mTOR pathway accompany the muscle phenotype. A conditional mouse model selectively depleted of Mecp2 in skeletal muscles is characterized by healthy muscles that are morphologically and molecularly indistinguishable from those of wild-type mice raising the possibility that hypotonia in RTT is mainly, if not exclusively, mediated by non-cell autonomous effects. Our results suggest that defects in paracrine/endocrine signaling and, in particular, in the GH/IGF axis appear as the major cause of the observed muscular defects. Remarkably, this is the first study describing the selective deletion of Mecp2 outside the brain. Similar future studies will permit to unambiguously define the direct impact of MeCP2 on tissue dysfunctions.

Biomarkers of peripheral muscle fatigue during exercise

PubMed Central

2012-01-01

Background Biomarkers of peripheral muscle fatigue (BPMFs) are used to offer insights into mechanisms of exhaustion during exercise in order to detect abnormal fatigue or to detect defective metabolic pathways. This review aims at describing recent advances and future perspectives concerning the most important biomarkers of muscle fatigue during exercise. Results BPMFs are classified according to the mechanism of fatigue related to adenosine-triphosphate-metabolism, acidosis, or oxidative-metabolism. Muscle fatigue is also related to an immunological response. impaired calcium handling, disturbances in bioenergetic pathways, and genetic responses. The immunological and genetic response may make the muscle susceptible to fatigue but may not directly cause muscle fatigue. Production of BPMFs is predominantly dependent on the type of exercise. BPMFs need to change as a function of the process being monitored, be stable without appreciable diurnal variations, correlate well with exercise intensity, and be present in detectable amounts in easily accessible biological fluids. The most well-known BPMFs are serum lactate and interleukin-6. The most widely applied clinical application is screening for defective oxidative metabolism in mitochondrial disorders by means of the lactate stress test. The clinical relevance of most other BPMFs, however, is under debate, since they often depend on age, gender, physical fitness, the energy supply during exercise, the type of exercise needed to produce the BPMF, and whether healthy or diseased subjects are investigated. Conclusions Though the role of BPMFs during fatigue is poorly understood, measuring BPMFs under specific, standardised conditions appears to be helpful for assessing biological states or processes during exercise and fatigue. PMID:23136874

Homology of the jaw muscles in lizards and snakes-a solution from a comparative gnathostome approach.

PubMed

Johnston, Peter

2014-03-01

Homology or shared evolutionary origin of jaw adductor muscles in lizards and snakes has been difficult to establish, although snakes clearly arose within the lizard radiation. Lizards typically have temporal adductors layered lateral to medial, and in snakes the muscles are arranged in a rostral to caudal pattern. Recent work has suggested that the jaw adductor group in gnathostomes is arranged as a folded sheet; when this theory is applied to snakes, homology with lizard morphology can be seen. This conclusion revisits the work of S.B. McDowell, J Herpetol 1986; 20:353-407, who proposed that homology involves identity of m. levator anguli oris and the loss of m. adductor mandibulae externus profundus, at least in "advanced" (colubroid) snakes. Here I advance the folded sheet hypothesis across the whole snake tree using new and literature data, and provide a solution to this homology problem. Copyright © 2014 Wiley Periodicals, Inc.

Muscle stem cell dysfunction impairs muscle regeneration in a mouse model of Down syndrome.

PubMed

Pawlikowski, Bradley; Betta, Nicole Dalla; Elston, Tiffany; Williams, Darian A; Olwin, Bradley B

2018-03-09

Down syndrome, caused by trisomy 21, is characterized by a variety of medical conditions including intellectual impairments, cardiovascular defects, blood cell disorders and pre-mature aging phenotypes. Several somatic stem cell populations are dysfunctional in Down syndrome and their deficiencies may contribute to multiple Down syndrome phenotypes. Down syndrome is associated with muscle weakness but skeletal muscle stem cells or satellite cells in Down syndrome have not been investigated. We find that a failure in satellite cell expansion impairs muscle regeneration in the Ts65Dn mouse model of Down syndrome. Ts65Dn satellite cells accumulate DNA damage and over express Usp16, a histone de-ubiquitinating enzyme that regulates the DNA damage response. Impairment of satellite cell function, which further declines as Ts65Dn mice age, underscores stem cell deficiencies as an important contributor to Down syndrome pathologies.

A Biomechanical Modeling Study of the Effects of the Orbicularis Oris Muscle and Jaw Posture on Lip Shape

ERIC Educational Resources Information Center

Stavness, Ian; Nazari, Mohammad Ali; Perrier, Pascal; Demolin, Didier; Payan, Yohan

2013-01-01

Purpose: The authors' general aim is to use biomechanical models of speech articulators to explore how possible variations in anatomical structure contribute to differences in articulatory strategies and phone systems across human populations. Specifically, they investigated 2 issues: (a) the link between lip muscle anatomy and variability in…

Functional reconstruction of total lower lip defects using innervated gracilis flap in the setting of high-energy ballistic injury to the lower face: preliminary report.

PubMed

Gurunluoglu, Raffi; Glasgow, Mark; Williams, Susan A; Gurunluoglu, Aslin; Antrobus, Jarod; Eusterman, Vincent

2012-10-01

Reconstruction of total full-thickness lower lip defects combined with extensive composite mandibular defects particularly in the setting of close-range high-energy ballistic injury presents a formidable challenge for the reconstructive plastic surgeon. While the fibular flap has been widely accepted for its usefulness in the reconstruction of composite mandibular defects, to date, there is no definitive widely established method of total lower lip reconstruction. The article presents authors' approach using innervated gracilis muscle flap for total lower lip reconstruction in the setting of high-energy gunshot injuries to the face. Three patients underwent composite mandibular defect reconstruction using fibular osteocutaneous flap and functional lower lip reconstruction using innervated gracilis muscle flap. Lip lining was reconstructed using the skin paddle of the fibular flap. The external surface of the gracilis muscle was skin-grafted. Facial artery myomucosal flap provided vermilion reconstruction in two patients. All fibular (n=3) and gracilis flap transfers (n=3) were viable. An electromyographic study at 1 year postoperatively demonstrated successful re-innervation of the gracilis muscle. Starting at about 10 weeks postoperatively, patients exhibited voluntary lip movements and oral competence. In addition, all patients achieved near-normal speech, evidence of recovered protective sensitivity and satisfactory appearance. The mean follow-up was 16.1 months. Our preliminary report in three patients demonstrated that innervated gracilis muscle transfer combined with fibular flap provides a successful reconstruction of extensive composite mandibular and total lower lip defects resulting from gunshot injuries to the face. Oral continence was achieved by combination of regained tonicity and voluntary movement of the gracilis muscle following re-innervation and assistance of the cheek muscles on the gracilis muscle. The described technique was reliable and the

The relationship between socially-assigned ethnicity, health and experience of racial discrimination for Māori: analysis of the 2006/07 New Zealand Health Survey

PubMed Central

2013-01-01

Background In New Zealand, there are significant and long-standing inequalities in a range of health outcomes, risk factors and healthcare measures between Māori (indigenous peoples) and Pākehā (European). This study expands our understanding of racism as a determinant of such inequalities to examine the concept of socially-assigned ethnicity (how an individual is classified by others ethnically/racially) and its relationship to health and racism for Māori. There is some evidence internationally that being socially-assigned as the dominant ethnic group (in this case European) offers health advantage. Methods We analysed data from the 2006/07 New Zealand Health Survey for adult participants who self-identified their ethnicity as Māori (n = 3160). The association between socially-assigned ethnicity and individual experience of racial discrimination, and socially-assigned ethnicity and health (self-rated health, psychological distress [Kessler 10-item scale]) was assessed using logistic and linear regression analyses, respectively. Results Māori who were socially-assigned as European-only had significantly lower experience of racial discrimination (adjusted odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.44, 0.78) than Māori who were socially-assigned as non-European. Being socially-assigned as European-only was also associated with health advantage compared to being socially-assigned non-European: more likely to respond with self-rated very good/excellent health (age, sex adjusted OR = 1.39, 95% CI = 1.10, 1.74), and lower Kessler 10 scores (age, sex adjusted mean difference = -0.66, 95% C I = -1.22, -0.10). These results were attenuated following adjustment for socioeconomic measures and experience of racial discrimination. Conclusions Results suggest that, in a race conscious society, the way people’s ethnicities are viewed by others is associated with tangible health risk or advantage, and this is consistent with an

The use of a latissimus dorsi muscle flap for scapular reconstruction in a cat following fibrosarcoma excision.

PubMed

Canapp, S O; Mann, F A; Henry, C J; Lattimer, J C

2001-01-01

A latissimus dorsi muscle flap was used to reconstruct a proximal scapular defect in a cat after excision of a fibrosarcoma that had recurred after eight surgeries, radiation therapy, and chemotherapy. To obtain appropriate surgical margins, infraspinatus and supraspinatus myectomy and scapular spinous ostectomy were performed. The latissimus dorsi muscle flap was rotated into the defect and anchored to four holes placed in the cranial border of the scapula. The cat showed no lameness at 6, 21, 42, and 147 days after surgery. The latissimus dorsi muscle flap was successful for proximal scapular reconstruction in this cat.

Dolichol-phosphate mannose synthase depletion in zebrafish leads to dystrophic muscle with hypoglycosylated α-dystroglycan.

PubMed

Marchese, Maria; Pappalardo, Andrea; Baldacci, Jacopo; Verri, Tiziano; Doccini, Stefano; Cassandrini, Denise; Bruno, Claudio; Fiorillo, Chiara; Garcia-Gil, Mercedes; Bertini, Enrico; Pitto, Letizia; Santorelli, Filippo M

2016-08-12

Defective dolichol-phosphate mannose synthase (DPMS) complex is a rare cause of congenital muscular dystrophy associated with hypoglycosylation of alpha-dystroglycan (α-DG) in skeletal muscle. We used the zebrafish (Danio rerio) to model muscle abnormalities due to defects in the subunits of DPMS. The three zebrafish ortholog subunits (encoded by the dpm1, dpm2 and dpm3 genes, respectively) showed high similarity to the human proteins, and their expression displayed localization in the midbrain/hindbrain area and somites. Antisense morpholino oligonucleotides targeting each subunit were used to transiently deplete the dpm genes. The resulting morphant embryos showed early death, muscle disorganization, low DPMS complex activity, and increased levels of apoptotic nuclei, together with hypoglycosylated α-DG in muscle fibers, thus recapitulating most of the characteristics seen in patients with mutations in DPMS. Our results in zebrafish suggest that DPMS plays a role in stabilizing muscle structures and in apoptotic cell death. Copyright © 2016 Elsevier Inc. All rights reserved.

Implantation of In Vitro Tissue Engineered Muscle Repair Constructs and Bladder Acellular Matrices Partially Restore In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss Injury

DTIC Science & Technology

2014-01-01

thickness abdominal wall defects. Tissue Eng 12, 1929, 2006. 7. Gamba, P.G., Conconi, M.T., Lo Piccolo, R., Zara , G., Spi nazzi, R., and Parnigotto... Zara , G., Sabatti, M., Marzaro, M., et al. Homologous muscle acellular matrix seeded with autologous myoblasts as a tissue engineering approach to

Loss of Notch2 and Notch3 in vascular smooth muscle causes patent ductus arteriosus.

PubMed

Baeten, Jeremy T; Jackson, Ashley R; McHugh, Kirk M; Lilly, Brenda

2015-12-01

The overlapping roles of the predominant Notch receptors in vascular smooth muscle cells, Notch2 and Notch3, have not been clearly defined in vivo. In this study, we use a smooth muscle-specific deletion of Notch2 together with a global Notch3 deletion to produce mice with combinations of mutant and wild-type Notch2/3 alleles in vascular smooth muscle cells. Mice with complete loss of Notch3 and smooth muscle-expressed Notch2 display late embryonic lethality and subcutaneous hemorrhage. Mice without smooth muscle-Notch2 and only one wild-type copy of Notch3 die within one day of birth and present with vascular defects, most notably patent ductus arteriosus (DA) and aortic dilation. These defects were associated with decreased expression of contractile markers in both the DA and aorta. These results demonstrate that Notch2 and Notch3 have overlapping roles in promoting development of vascular smooth muscle cells, and together contribute to functional closure of the DA. © 2015 Wiley Periodicals, Inc.

Reconstruction of maxillary defect with musculo-adipose rectus free flap.

PubMed

Low, Tsu-Hui Hubert; Lindsay, Andrew; Clark, Jonathan; Chai, Francis; Lewis, Richard

2017-02-01

The rectus myocutaneous free flap (RMFF) is used for medium to large maxillectomy defects. However, in patients with central obesity the inset could be difficult due to the bulk from excessive layer of adipose tissue. We describe a modification of the RMFF for patients with excessive central obesity with a flap consisting of adipose tissue with minimal rectus muscle; the musculo-adipose rectus free flap (MARF). Five cases of MARF reconstruction were performed between 2003 and 2013, with patients' body mass indexes ranging from 29.0 to 41.2 kg/m 2 . All patients had sinonasal tumor, of which three were adenoid cystic carcinoma, one squamous cell carcinoma, and one melanoma. Four patients had Codeiro IIIb defects and one had Codeiro II defect. Using the MARF technique, the maxillectomy defect was obliterated with vascularized adipose tissue overlying the rectus muscle and was trimmed to fit the maxillectomy defect. The adipose tissue was allowed to granulate and mucosalize. The volume of adipose tissue harvested was between 120 and 160 mL. All flaps survived with no requirement for re-exploration. Complete oro-nasal separation was achieved in all patients. The time to commencement of oral intake ranges from 5 to 15 days. One patient developed seroma and one developed wound breakdown on the donor site. The length of stay at the hospital ranges from 9 to 22 days. On follow-up ranging 7.5-32.8 months, two patients died from their malignancies. The other three patients were able to tolerate oral soft diet. The MARF may be considered as an alternative to myocutaneous rectus free flap particularly for the reconstruction of maxillary defects in patients with central obesity. © 2015 Wiley Periodicals, Inc. Microsurgery 37:137-141, 2017. © 2015 Wiley Periodicals, Inc.

Optimizing Soft Tissue Management and Spacer Design in Segmental Bone Defects

DTIC Science & Technology

2016-12-01

proximal and distal bone segments. 3. Debride 10 grams of tibialis anterior and gastrocnemius muscles. 4. Place an interlocking intramedullary nail ...using a custom spacer to maintain 5-cm defect length. 5. Place a pre-molded 5 cm long x 2 cm diameter PMMA spacer around the nail in the defect. 6...tibia. 3. Open the IM surrounding the PMMA spacer using a “bomb bay door opening”. 4. Remove the spacer without damaging the membrane or nail . 5

Store-Operated Ca2+ Entry (SOCE) Contributes to Normal Skeletal Muscle Contractility in young but not in aged skeletal muscle

PubMed Central

Brotto, Leticia S.; Bougoin, Sylvain; Nosek, Thomas M.; Reid, Michael; Hardin, Brian; Pan, Zui; Ma, Jianjie; Parness, Jerome

2011-01-01

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca2+ to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca2+ entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca2+ to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca2+ release channel-mediated Ca2+ release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca2+ entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle. PMID:21666285

Co-delivery of a laminin-111 supplemented hyaluronic acid based hydrogel with minced muscle graft in the treatment of volumetric muscle loss injury

PubMed Central

Goldman, Stephen M.; Henderson, Beth E. P.; Walters, Thomas J.

2018-01-01

Minced muscle autografting mediates de novo myofiber regeneration and promotes partial recovery of neuromuscular strength after volumetric muscle loss injury (VML). A major limitation of this approach is the availability of sufficient donor tissue for the treatment of relatively large VMLs without inducing donor site morbidity. This study evaluated a laminin-111 supplemented hyaluronic acid based hydrogel (HA+LMN) as a putative myoconductive scaffolding to be co-delivered with minced muscle grafts. In a rat tibialis anterior muscle VML model, delivery of a reduced dose of minced muscle graft (50% of VML defect) within HA+LMN resulted in a 42% improvement of peak tetanic torque production over unrepaired VML affected limbs. However, the improvement in strength was not improved compared to a 50% minced graft-only control group. Moreover, histological analysis revealed that the improvement in in vivo functional capacity mediated by minced grafts in HA+LMN was not accompanied by a particularly robust graft mediated regenerative response as determined through donor cell tracking of the GFP+ grafting material. Characterization of the spatial distribution and density of macrophage and satellite cell populations indicated that the combination therapy damps the heightened macrophage response while re-establishing satellite content 14 days after VML to a level consistent with an endogenously healing ischemia-reperfusion induced muscle injury. Moreover, regional analysis revealed that the combination therapy increased satellite cell density mostly in the remaining musculature, as opposed to the defect area. Based on the results, the following salient conclusions were drawn: 1) functional recovery mediated by the combination therapy is likely due to a superposition of de novo muscle fiber regeneration and augmented repair of muscle fibers within the remaining musculature, and 2) The capacity for VML therapies to augment regeneration and repair within the remaining musculature

Androgen receptor polyglutamine expansion drives age-dependent quality control defects and muscle dysfunction.

PubMed

Nath, Samir R; Yu, Zhigang; Gipson, Theresa A; Marsh, Gregory B; Yoshidome, Eriko; Robins, Diane M; Todi, Sokol V; Housman, David E; Lieberman, Andrew P

2018-05-29

Skeletal muscle has emerged as a critical, disease-relevant target tissue in spinal and bulbar muscular atrophy, a degenerative disorder of the neuromuscular system caused by a CAG/polyglutamine (polyQ) expansion in the androgen receptor (AR) gene. Here, we used RNA-Seq to identify pathways that are disrupted in diseased muscle using AR113Q knock-in mice. This analysis unexpectedly identified significantly diminished expression of numerous ubiquitin-proteasome pathway genes in AR113Q muscle, encoding approximately 30% of proteasome subunits and 20% of E2 ubiquitin conjugases. These changes were age-, hormone- and glutamine length-dependent and arose due to a toxic gain-of-function conferred by the mutation. Moreover, altered gene expression was associated with decreased level of the proteasome transcription factor NRF1 and its activator DDI2 and resulted in diminished proteasome activity. Ubiquitinated ADRM1 was detected in AR113Q muscle, indicating the occurrence of stalled proteasomes in mutant mice. Finally, diminished expression of Drosophila orthologues of NRF1 or ADRM1 promoted the accumulation of polyQ AR protein and increased toxicity. Collectively, these data indicate that AR113Q muscle develops progressive proteasome dysfunction that leads to the impairment of quality control and the accumulation of polyQ AR protein, key features that contribute to the age-dependent onset and progression of this disorder.

Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism.

PubMed

Lerin, Carles; Goldfine, Allison B; Boes, Tanner; Liu, Manway; Kasif, Simon; Dreyfuss, Jonathan M; De Sousa-Coelho, Ana Luisa; Daher, Grace; Manoli, Irini; Sysol, Justin R; Isganaitis, Elvira; Jessen, Niels; Goodyear, Laurie J; Beebe, Kirk; Gall, Walt; Venditti, Charles P; Patti, Mary-Elizabeth

2016-10-01

Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

DM ORI: A YOUNG STAR OCCULTED BY A DISTURBANCE IN ITS PROTOPLANETARY DISK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez, Joseph E.; Stassun, Keivan G.; Lund, Michael B.

In some planet formation theories, protoplanets grow gravitationally within a young star’s protoplanetary disk, a signature of which may be a localized disturbance in the disk’s radial and/or vertical structure. Using time-series photometric observations by the Kilodegree Extremely Little Telescope South project and the All-Sky Automated Survey for SuperNovae, combined with archival observations, we present the discovery of two extended dimming events of the young star, DM Ori. This young system faded by ∼1.5 mag from 2000 March to 2002 August and then again in 2013 January until 2014 September (depth ∼1.7 mag). We constrain the duration of the 2000–2002more » dimming to be < 860 days, and the event in 2013–2014 to be < 585 days, separated by ∼12.5 years. A model of the spectral energy distribution indicates a large infrared excess consistent with an extensive circumstellar disk. Using basic kinematic arguments, we propose that DM Ori is likely being periodically occulted by a feature (possibly a warp or perturbation) in its circumstellar disk. In this scenario, the occulting feature is located >6 au from the host star, moving at ∼14.6 km s{sup −1} and is ∼4.9 au in width. This localized structure may indicate a disturbance such as that which may be caused by a protoplanet early in its formation.« less

Paravaginal defect: anatomy, clinical findings, and imaging

PubMed Central

Arenholt, Louise T.S.; Pedersen, Bodil Ginnerup; Glavind, Karin; Glavind-Kristensen, Marianne; DeLancey, John O.L.

2017-01-01

Introduction and Hypothesis The paravaginal defect has been a topic of active discussion concerning 1) what it is; 2) how to diagnose it; 3) its role in anterior vaginal wall prolapse; and 4) if and how to repair it. The aim of this article is to review the existing literature on the paravaginal defect and to discuss its role in the anterior vaginal wall support system, with an emphasis on anatomy and imaging. Methods Articles related to paravaginal defects were identified through a PUBMED search ending July 1, 2015. Results The support of the anterior vaginal wall is a complex system involving the levator ani muscle, the arcus tendineus fascia pelvis (ATFP), the pubocervical fascia, and the uterosacral/cardinal ligaments. Studies conclude that physical examination is inconsistent in detecting paravaginal defects. Ultrasound (US) and magnetic resonance imaging (MRI) have been used to describe patterns in the appearance of the vagina and bladder when a paravaginal defect is suspected. Different terms have been used (e.g. “sagging of bladder base,” “loss of tenting”), which all represent changes in the support of the pelvic floor but which could be due to both paravaginal defects and levator ani defects. Conclusion Paravaginal support plays a role in the support of the anterior vaginal wall, but we still do not know the degree to which it contributes to the development of prolapse. Both MRI and US are useful in the diagnosis of paravaginal defects, but further studies are needed to evaluate their use. PMID:27640064

A contracting circumbinary molecular ring around Ori 139-409 with an inner cavity of about 140 au

NASA Astrophysics Data System (ADS)

Zapata, Luis A.; Schilke, Peter; Ho, Paul T. P.

2010-03-01

We present sensitive and subarcsecond resolution (~0.7 arcsec) CH3OH(7-2,6-6-2,5) line and 890-μm continuum observations, made with the Submillimeter Array (SMA), towards the hot molecular circumbinary ring associated with the young multiple star Ori 139-409. The CH3OH(7-2,6-6-2,5) emission from the ring is well resolved at this angular resolution, revealing an inner cavity with a size of about 140 au. A local thermodynamic equilibrium model of a Keplerian disc with an inner cavity of the same size confirms the presence of this cavity. Additionally, this model suggests that the circumbinary ring is contracting with a velocity of Vinf ~ 1.5kms-1 towards the binary central compact circumstellar discs reported at a wavelength of 7 mm. The inner central cavity seems to be formed by the tidal effects of the young stars in the middle of the ring. The ring does not appear to be a stationary object. Furthermore, the infall velocity we determine is about a factor of 3 slower than the free-fall velocity corresponding to the dynamical mass. This would correspond to a mass accretion rate of about 10-5 Msolar yr-1. We have found that the dust emission associated with Ori 139-409 appears to be arising from the circumstellar discs, with no strong contribution from the molecular gas ring. Furthermore, a simple comparison with other classical molecular dusty rings (e.g. GG Tau, UZ Tau and UY Aur) suggests that Ori 139-409 could be one of the youngest circumbinary rings reported to date. Finally, our results confirm that the circumbinary rings are actively funnelling fresh gas material to the central compact binary circumstellar discs (i.e. to the protostars in the very early phases of their evolution).

Whakawhiti Kōrero, a Method for the Development of a Cultural Assessment Tool, Te Waka Kuaka, in Māori Traumatic Brain Injury.

PubMed

Elder, Hinemoa; Kersten, Paula

2015-01-01

The importance of tools for the measurement of outcomes and needs in traumatic brain injury is well recognised. The development of tools for these injuries in indigenous communities has been limited despite the well-documented disparity of brain injury. The wairua theory of traumatic brain injury (TBI) in Māori proposes that a culturally defined injury occurs in tandem with the physical injury. A cultural response is therefore indicated. This research investigates a Māori method used in the development of cultural needs assessment tool designed to further examine needs associated with the culturally determined injury and in preparation for formal validation. Whakawhiti kōrero is a method used to develop better statements in the development of the assessment tool. Four wānanga (traditional fora) were held including one with whānau (extended family) with experience of traumatic brain injury. The approach was well received. A final version, Te Waka Kuaka, is now ready for validation. Whakawhiti kōrero is an indigenous method used in the development of cultural needs assessment tool in Māori traumatic brain injury. This method is likely to have wider applicability, such as Mental Health and Addictions Services, to ensure robust process of outcome measure and needs assessment development.

Co-delivery of micronized urinary bladder matrix damps regenerative capacity of minced muscle grafts in the treatment of volumetric muscle loss injuries

PubMed Central

Corona, Benjamin T.

2017-01-01

Minced muscle grafts (MG) promote de novo muscle fiber regeneration and neuromuscular strength recovery in small and large animal models of volumetric muscle loss. The most noteworthy limitation of this approach is its reliance on a finite supply of donor tissue. To address this shortcoming, this study sought to evaluate micronized acellular urinary bladder matrix (UBM) as a scaffolding to promote in vivo expansion of this MG therapy in a rat model. Rats received volumetric muscle loss injuries to the tibialis anterior muscle of their left hind limb which were either left untreated or repaired with minced muscle graft at dosages of 50% and 100% of the defect mass, urinary bladder matrix in isolation, or a with an expansion product consisting of a combination of the two putative therapies in which the minced graft is delivered at a dosage of 50% of the defect mass. Rats survived to 2 and 8 weeks post injury before functional (in vivo neuromuscular strength), histological, morphological, and biochemical analyses were performed. Rats treated with the expansion product exhibited improved neuromuscular function relative to untreated VML after an 8 week time period following injury. This improvement in functional capacity, however, was accompanied with a concomitant reduction in graft mediated regeneration, as evidenced cell lineage tracing enable by a transgenic GFP expressing donor, and a mixed histological outcome indicating coincident fibrous matrix deposition with interspersed islands of nascent muscle fibers. Furthermore, quantitative immunofluorescence and transcriptional analysis following the 2 week time point suggests an exacerbated immune response to the UBM as a possible nidus for the observed suboptimal regenerative outcome. Moving forward, efforts related to the development of a MG expansion product should carefully consider the effects of the host immune response to candidate biomaterials in order to avoid undesirable dysregulation of pro

Repair of tracheomalacia with inflammatory defect and mediastinitis.

PubMed

Sandu, Kishore; Monnier, Yan; Hurni, Michel; Bernath, Marc-Andre; Monnier, Philippe; Wang, Yabo; Ris, Hans-Beat

2011-01-01

We describe a novel repair of an anterior inflammatory tracheal defect with mediastinitis, which occurred after external tracheal suspension of localized intrathoracic tracheomalacia. The malacic tracheal segment of 4-cm length containing the inflammatory tracheal defect was noncircumferentially resected. A temporary endotracheal silicone stent was introduced, and the trachea was closed by a pedicled pectoralis muscle flap reinforced with an embedded rib segment. Retrieval of the stent 5 months postoperatively resulted in a re-epithelialized, persistently stable, noncollapsible tracheal segment that showed the same diameter and configuration as the nonreconstructed part of the trachea. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Cavin4b/Murcb Is Required for Skeletal Muscle Development and Function in Zebrafish.

PubMed

Housley, Michael P; Njaine, Brian; Ricciardi, Filomena; Stone, Oliver A; Hölper, Soraya; Krüger, Marcus; Kostin, Sawa; Stainier, Didier Y R

2016-06-01

Skeletal muscles provide metazoans with the ability to feed, reproduce and avoid predators. In humans, a heterogeneous group of genetic diseases, termed muscular dystrophies (MD), lead to skeletal muscle dysfunction. Mutations in the gene encoding Caveolin-3, a principal component of the membrane micro-domains known as caveolae, cause defects in muscle maintenance and function; however it remains unclear how caveolae dysfunction underlies MD pathology. The Cavin family of caveolar proteins can form membrane remodeling oligomers and thus may also impact skeletal muscle function. Changes in the distribution and function of Cavin4/Murc, which is predominantly expressed in striated muscles, have been reported to alter caveolae structure through interaction with Caveolin-3. Here, we report the generation and phenotypic analysis of murcb mutant zebrafish, which display impaired swimming capacity, skeletal muscle fibrosis and T-tubule abnormalities during development. To understand the mechanistic importance of Murc loss of function, we assessed Caveolin-1 and 3 localization and found it to be abnormal. We further identified an in vivo function for Murc in Erk signaling. These data link Murc with developmental defects in T-tubule formation and progressive muscle dysfunction, thereby providing a new candidate for the etiology of muscular dystrophy.

Cavin4b/Murcb Is Required for Skeletal Muscle Development and Function in Zebrafish

PubMed Central

Housley, Michael P.; Njaine, Brian; Ricciardi, Filomena; Stone, Oliver A.; Hölper, Soraya; Krüger, Marcus; Kostin, Sawa; Stainier, Didier Y. R.

2016-01-01

Skeletal muscles provide metazoans with the ability to feed, reproduce and avoid predators. In humans, a heterogeneous group of genetic diseases, termed muscular dystrophies (MD), lead to skeletal muscle dysfunction. Mutations in the gene encoding Caveolin-3, a principal component of the membrane micro-domains known as caveolae, cause defects in muscle maintenance and function; however it remains unclear how caveolae dysfunction underlies MD pathology. The Cavin family of caveolar proteins can form membrane remodeling oligomers and thus may also impact skeletal muscle function. Changes in the distribution and function of Cavin4/Murc, which is predominantly expressed in striated muscles, have been reported to alter caveolae structure through interaction with Caveolin-3. Here, we report the generation and phenotypic analysis of murcb mutant zebrafish, which display impaired swimming capacity, skeletal muscle fibrosis and T-tubule abnormalities during development. To understand the mechanistic importance of Murc loss of function, we assessed Caveolin-1 and 3 localization and found it to be abnormal. We further identified an in vivo function for Murc in Erk signaling. These data link Murc with developmental defects in T-tubule formation and progressive muscle dysfunction, thereby providing a new candidate for the etiology of muscular dystrophy. PMID:27294373

X-ray, UV and optical analysis of supergiants: ɛ Ori

NASA Astrophysics Data System (ADS)

Puebla, Raul E.; Hillier, D. John; Zsargó, Janos; Cohen, David H.; Leutenegger, Maurice A.

2016-03-01

We present a multi-wavelength (X-ray to optical) analysis, based on non-local thermodynamic equilibrium photospheric+wind models, of the B0 Ia-supergiant: ɛ Ori. The aim is to test the consistency of physical parameters, such as the mass-loss rate and CNO abundances, derived from different spectral bands. The derived mass-loss rate is {dot {M}} / {√{f_{∞}}} {˜} 1.6 × 10-6 M⊙ yr-1 where f∞ is the volume filling factor. However, the S IV λλ1062,1073 profiles are too strong in the models; to fit the observed profiles it is necessary to use f∞ <0.01. This value is a factor of 5 to 10 lower than inferred from other diagnostics, and implies {dot{M}} ≲ 1 × 10^{-7} M⊙ yr-1. The discrepancy could be related to porosity-vorosity effects or a problem with the ionization of sulphur in the wind. To fit the UV profiles of N V and O VI it was necessary to include emission from an interclump medium with a density contrast (ρcl/ρICM) of ˜100. X-ray emission in H/He like and Fe L lines was modelled using four plasma components located within the wind. We derive plasma temperatures from 1 × 106 to 7 × 106 K, with lower temperatures starting in the outer regions (R0 ˜ 3-6 R*), and a hot component starting closer to the star (R0 ≲ 2.9 R*). From X-ray line profiles we infer {dot{M}} < 4.9 × 10-7 M⊙ yr-1. The X-ray spectrum (≥0.1 kev) yields an X-ray luminosity LX ˜ 2.0 × 10-7Lbol, consistent with the superion line profiles. X-ray abundances are in agreement with those derived from the UV and optical analysis: ɛ Ori is slightly enhanced in nitrogen and depleted in carbon and oxygen, evidence for CNO processed material.

VizieR Online Data Catalog: Light curves of Algol-type binaries. VI. FR Ori (Yang+, 2014)

NASA Astrophysics Data System (ADS)

Yang, Y.-G.; Wei, J.-Y.; Li, H.-L.

2014-09-01

New photometry of FR Ori was performed in 2012 November (Nov 7-8 and Nov 16-20) and December (Dec 5-9), using the 60cm telescope at the Xinglong Station (XLs) of the National Astronomical Observatories of China (NAOC). A Princeton Instrument 1024*1024 CCD camera was mounted at this telescope. The standard Johnson/Cousins set of BVIR filters was applied. (3 data files).

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds.

PubMed

Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F; Furling, Denis

2017-04-01

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. © 2017. Published by The Company of Biologists Ltd.

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

PubMed Central

Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F.

2017-01-01

ABSTRACT Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. PMID:28188264

Re-animation of muscle flaps for improved function in dynamic myoplasty.

PubMed

Stremel, R W; Zonnevijlle, E D

2001-01-01

The authors report on a series of experiments designed to produce a skeletal muscle contraction functional for dynamic myoplasties. Conventional stimulation techniques recruit all or most of the muscle fibers simultaneously and with maximal strength. This approach has limitations in free dynamic muscle flap transfers that require the muscle to contract immediately after transfer and before re-innervation. Sequential stimulation of segments of the transferred muscle provides a means of producing non-fatiguing contractions of the muscle in the presence or absence of innervation. The muscles studied were the canine gracilis, and all experiments were acute studies in anesthetized animals. Comparison of conventional and sequential segmental neuromuscular stimulation revealed an increase in muscle fatigue resistance and muscle blood flow with the new approach. This approach offers the opportunity for development of physiologically animated tissue and broadening the abilities of reconstructive surgeons in the repair of functional defects. Copyright 2001 Wiley-Liss, Inc.

Superior ophthalmic vein enlargement and increased muscle index in dysthyroid optic neuropathy.

PubMed

Lima, Breno da Rocha; Perry, Julian D

2013-01-01

To compare superior ophthalmic vein diameter and extraocular muscle index in patients with thyroid eye disease with or without optic neuropathy. High-resolution CT scan images of 40 orbits of 20 patients with history of thyroid eye disease (with or without optic neuropathy), who underwent orbital decompression surgery from January 2007 to November 2009, were retrospectively reviewed. Superior ophthalmic vein diameter was measured in coronal and axial planes. Extraocular muscle index was calculated according to the method proposed by Barrett et al. The clinical diagnosis of optic neuropathy was based on characteristic signs that included afferent pupillary defect, decreased visual acuity, visual field defects, and dyschromatopsia. Orbits were divided in 2 groups based on presence or absence of optic neuropathy. Superior ophthalmic vein diameter was significantly higher in orbits with concomitant optic neuropathy (mean 2.4 ± 0.4mm, p < 0.0001). Increased muscle index was also related to optic neuropathy (mean 57.9% ± 5.7%, p = 0.0002). Muscle index greater than 50% was present in all patients with dysthyroid optic neuropathy. This study suggests that patients with thyroid eye disease with enlarged superior ophthalmic vein and increased extraocular muscle index are more likely to have concomitant optic neuropathy.

[Muscle biopsy in children: Usefulness in 2012].

PubMed

Cuisset, J-M; Maurage, C-A; Carpentier, A; Briand, G; Thévenon, A; Rouaix, N; Vallée, L

2013-01-01

Muscle biopsy is a mainstay diagnostic tool for investigating neuromuscular disorders in children. We report the yield of pediatric muscle biopsy in a population of 415 children by a retrospective study of 419 biopsies performed between 1/01/2000 and 31/12/2009 in a neuropediatric department, including mitochondrial respiratory chain analysis for 87 children. Two hundred and fifty-five biopsies were from boys (61%) 164 from girls (39%). Their mean age at biopsy was 6.5years; 155 (37%) biopsies were obtained before the child was 5years old. Final histopathological diagnoses were: congenital myopathy (n=193, including 15 structural congenital myopathies); progressive muscular dystrophy (n=75 [18%] including 57 dystrophinopathies); congenital muscular dystrophy (n=17, including six primary merosinopathies); dermatomyositis (n=11); spinal muscular atrophy (n=9, including six atypical spinal muscular atrophies); metabolic myopathy (n=32, including 19 mitochondrial myopathies); encephalomyopathy (n=53 [13%], including 27 with a mitochondrial respiratory chain defect). Pathological diagnosis remained undetermined in 16 cases. In 184 patients (44%), the muscle biopsy revealed specific histopathological anomalies (dystrophic process; specific ultrastructural abnormalities; perifascicular atrophy; neurogenic atrophy; metabolic anomalies) enabling a precise etiological diagnosis. For 85% of progressive muscular dystrophies, the biopsy resulted in a genetic diagnosis after identification of the protein defect. In 15% of the congenital myopathies, histopathological anomalies focused attention on one or several genes. Concerning dystrophinopathies, quantification of dystrophin deficiency on the biopsy specimen contributed to the definition of the clinical phenotype: Duchenne, or Becker. In children with a myopathy, muscle biopsy is often indispensable to establish the etiological diagnosis. Based on the results from this series, muscle biopsy can provide a precise

"Ode Ori": a culture-bound disorder with prominent somatic features in Yoruba Nigerian patients.

PubMed

Makanjuola, R O

1987-03-01

Thirty patients diagnosed by Nigerian Yoruba traditional healers as suffering from a condition termed "Ode Ori" are described. The chief complaints were of a crawling sensation in the head and body, noises in the ears, palpitations and various other somatic complaints. Anxiety and depressive symptoms were prominent in all the patients and indeed the most common DSM-III diagnoses were of depressive and anxiety disorders. The significance of the disorder and its features is discussed in the context of the socio-cultural background of the patients.

Reconstruction of maxillectomy and midfacial defects with free tissue transfer.

PubMed

Santamaria, Eric; Cordeiro, Peter G

2006-11-01

The maxillary bones are part of the midfacial skeleton and are closely related to the eyeglobe, nasal airway, and oral cavity. Together with the overlying soft tissues, the two maxillae are responsible to a large extent for facial contour. Maxillectomy defects become more complex when critical structures such as the orbit, globe, and cranial base are resected, and reconstruction with distant tissues become essential. In this article, we describe a classification system and algorithm for reconstruction of these complex defects using various pedicled and free flaps. Most defects that involve resection of the maxilla and adjacent soft tissues may be classified into one of the following four types: Type I defects, Limited maxillectomy; Type II defects, Subtotal maxillectomy; Type III defects, Total maxillectomy; and Type IV defects, Orbitomaxillectomy. Using this classification, reconstruction of maxillectomy and midfacial defects may be approached considering the relationship between volume and surface area requirements, that is, addressing the bony defect first, followed by assessment of the associated soft tissue, skin, palate, and cheek-lining deficits. In our experience, most complex maxillectomy defects are best reconstructed using free tissue transfer. The rectus abdominis and radial forearm free flap in combination with immediate bone grafting or as an osteocutaneous flap reliably provide the best aesthetic and functional results. A temporalis muscle pedicled flap is used for reconstruction of maxillectomy defects only in those patients who are not candidates for a microsurgical procedure.

Reflex muscle contraction in anterior shoulder instability.

PubMed

Wallace, D A; Beard, D J; Gill, R H; Eng, B; Carr, A J

1997-01-01

Reduced proprioception may contribute to recurrent anterior shoulder instability. Twelve patients with unilateral shoulder instability were investigated for evidence of deficient proprioception with an activated pneumatic cylinder and surface electromyography electrodes; the contralateral normal shoulder was used as a control. The latency between onset of movement and the detection of muscle contraction was used as an index of proprioception. No significant difference in muscle contraction latency was detected between the stable and unstable shoulders, suggesting that there was no significant defect in muscular reflex activity. This study does not support the use proprioception-enhancing physiotherapy in the treatment of posttraumatic anterior shoulder instability.

The Protective Influence of Family Connectedness, Ethnic Identity, and Ethnic Engagement for New Zealand Ma¯ori Adolescents

ERIC Educational Resources Information Center

Stuart, Jaimee; Jose, Paul E.

2014-01-01

The present study examined the associations among family connectedness, ethnic identity, and ethnic engagement on changes in well-being over time for the understudied population of Ma¯ori (indigenous New Zealand) youth. Data were collected as part of a longitudinal study of youth connectedness in New Zealand using self-report measures at 3…

The effect of myotonic dystrophy transcript levels and location on muscle differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mastroyiannopoulos, Nikolaos P.; Chrysanthou, Elina; Kyriakides, Tassos C.

2008-12-12

In myotonic dystrophy type I (DM1), nuclear retention of mutant DMPK transcripts compromises muscle cell differentiation. Although several reports have identified molecular defects in myogenesis, it remains still unclear how exactly the retention of the mutant transcripts induces this defect. We have recently created a novel cellular model in which the mutant DMPK 3' UTR transcripts were released to the cytoplasm of myoblasts by using the WPRE genetic element. As a result, muscle cell differentiation was repaired. In this paper, this cellular model was further exploited to investigate the effect of the levels and location of the mutant transcripts onmore » muscle differentiation. Results show that the levels of these transcripts were proportional to the inhibition of both the initial fusion of myoblasts and the maturity of myotubes. Moreover, the cytoplasmic export of the mutant RNAs to the cytoplasm caused less inhibition only in the initial fusion of myoblasts.« less

The Gradual Expansion Muscle Flap

DTIC Science & Technology

2014-01-01

acute shortening and angulation of the tibia and rotational muscle flap coverage and split thickness skin grafting of the soft tissue defect...is also amenable to split-thickness skin grafting after tissue incorporation.11 In addition to donor site morbidity, free tissue transfer is dependent...necessary soft tissue coverage. In the second stage, after the flap has adequately set and overlying skin graft has full adherence, a Taylor Spatial

Observed Luminosity Spread in Young Clusters and FU Ori Stars: A Unified Picture

NASA Astrophysics Data System (ADS)

Baraffe, I.; Vorobyov, E.; Chabrier, G.

2012-09-01

The idea that non-steady accretion during the embedded phase of protostar evolution can produce the observed luminosity spread in the Herzsprung-Russell diagram (HRD) of young clusters has recently been called into question. Observations of FU Ori, for instance, suggest an expansion of the star during strong accretion events, whereas the luminosity spread implies a contraction of the accreting objects, decreasing their radiating surface. In this paper, we present a global scenario based on calculations coupling episodic accretion histories derived from numerical simulations of collapsing cloud prestellar cores of various masses and subsequent protostar evolution. Our calculations show that, assuming an initial protostar mass Mi ~ 1 M Jup, typical of the second Larson's core, both the luminosity spread in the HRD and the inferred properties of FU Ori events (mass, radius, accretion rate) can be explained by this scenario, providing two conditions. First, there must be some variation within the fraction of accretion energy absorbed by the protostar during the accretion process. Second, the range of this variation should increase with increasing accretion burst intensity and thus with the initial core mass and final star mass. The numerical hydrodynamics simulations of collapsing cloud prestellar cores indeed show that the intensity of the accretion bursts correlates with the mass and initial angular momentum of the prestellar core. Massive prestellar cores with high initial angular momentum are found to produce intense bursts characteristic of FU Ori-like events. Our results thus suggest a link between the burst intensities and the fraction of accretion energy absorbed by the protostar, with some threshold in the accretion rate, of the order of 10-5 M ⊙ yr-1, delimitating the transition from "cold" to "hot" accretion. Such a transition might reflect a change in the accretion geometry with increasing accretion rate, i.e., a transition from magnetospheric or thin

Synaptic defects associated with s-inclusion body myositis are prevented by copper.

PubMed

Aldunate, R; Minniti, A N; Rebolledo, D; Inestrosa, N C

2012-08-01

Sporadic-inclusion body myositis (s-IBM) is the most common skeletal muscle disorder to afflict the elderly, and is clinically characterized by skeletal muscle degeneration. Its progressive course leads to muscle weakness and wasting, resulting in severe disability. The exact pathogenesis of this disease is unknown and no effective treatment has yet been found. An intriguing aspect of s-IBM is that it shares several molecular abnormalities with Alzheimer's disease, including the accumulation of amyloid-β-peptide (Aβ). Both disorders affect homeostasis of the cytotoxic fragment Aβ(1-42) during aging, but they are clinically distinct diseases. The use of animals that mimic some characteristics of a disease has become important in the search to elucidate the molecular mechanisms underlying the pathogenesis. With the aim of analyzing Aβ-induced pathology and evaluating the consequences of modulating Aβ aggregation, we used Caenorhabditis elegans that express the Aβ human peptide in muscle cells as a model of s-IBM. Previous studies indicate that copper treatment increases the number and size of amyloid deposits in muscle cells, and is able to ameliorate the motility impairments in Aβ transgenic C. elegans. Our recent studies show that neuromuscular synaptic transmission is defective in animals that express the Aβ-peptide and suggest a specific defect at the nicotine acetylcholine receptors level. Biochemical analyses show that copper treatment increases the number of amyloid deposits but decreases Aβ-oligomers. Copper treatment improves motility, synaptic structure and function. Our results suggest that Aβ-oligomers are the toxic Aβ species that trigger neuromuscular junction dysfunction.

The Drosophila muscle LIM protein, Mlp84B, cooperates with D-titin to maintain muscle structural integrity.

PubMed

Clark, Kathleen A; Bland, Jennifer M; Beckerle, Mary C

2007-06-15

Muscle LIM protein (MLP) is a cytoskeletal LIM-only protein expressed in striated muscle. Mutations in human MLP are associated with cardiomyopathy; however, the molecular mechanism by which MLP functions is not established. A Drosophila MLP homolog, mlp84B, displays many of the same features as the vertebrate protein, illustrating the utility of the fly for the study of MLP function. Animals lacking Mlp84B develop into larvae with a morphologically intact musculature, but the mutants arrest during pupation with impaired muscle function. Mlp84B displays muscle-specific expression and is a component of the Z-disc and nucleus. Preventing nuclear retention of Mlp84B does not affect its function, indicating that Mlp84B site of action is likely to be at the Z-disc. Within the Z-disc, Mlp84B is colocalized with the N-terminus of D-titin, a protein crucial for sarcomere organization and stretch mechanics. The mlp84B mutants phenotypically resemble weak D-titin mutants. Furthermore, reducing D-titin activity in the mlp84B background leads to pronounced enhancement of the mlp84B muscle defects and loss of muscle structural integrity. The genetic interactions between mlp84B and D-titin reveal a role for Mlp84B in maintaining muscle structural integrity that was not obvious from analysis of the mlp84B mutants themselves, and suggest Mlp84B and D-titin cooperate to stabilize muscle sarcomeres.

Muscle response to leg lengthening during distraction osteogenesis.

PubMed

Thorey, Fritz; Bruenger, Jens; Windhagen, Henning; Witte, Frank

2009-04-01

Continuous lengthening of intact muscles during distraction osteogenesis leads to an increase of sarcomeres and enhances the regeneration of tendons and blood vessels. A high distraction rate leads to an excessive leg and muscle lengthening and might cause damages of muscle fibers with fibrosis, necrosis, and muscle weakness. Complications like muscle contractures or atrophy after postoperative immobilization emphazize the importance of muscles and their function in the clinical outcome. In an animal model of distraction osteogenesis, 18 sheep were operated with an external fixator followed by 4 days latency, 21 days distraction (1.25 mm per day) and 51 days consolidation. The anatomical location (gastrocnemius, peroneus tertius, and first flexor digitorum longus muscle), dimension and occurrence of muscular defects were characterized histologically. The callus formation and leg axis was monitored by weekly X-rays. Additionally, serum creatine kinase was analyzed during a distraction and consolidation period. Significant signs of muscle lesions in all three observed muscles can be found postoperatively, whereas normal callus formation and regular leg axis was observed radiologically. The peroneus tertius and first flexor digitorum longus muscles were found to have significantly more signs of fibrosis, inflammatory, and necrosis. Creatine kinase showed two peaks: 4 and 39 days postoperative as an indication of muscle damage and regeneration. The study implicates that muscle damages should be considered when a long-distance distraction osteogenesis is planned. The surgeon should consider these muscle responses and individually discuss a two-stage treatment or additional muscle tendon releases to minimize the risk of muscle damages.

Application of dynamic metabolomics to examine in vivo skeletal muscle glucose metabolism in the chronically high-fat fed mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kowalski, Greg M., E-mail: greg.kowalski@deakin.edu.au; De Souza, David P.; Burch, Micah L.

Rationale: Defects in muscle glucose metabolism are linked to type 2 diabetes. Mechanistic studies examining these defects rely on the use of high fat-fed rodent models and typically involve the determination of muscle glucose uptake under insulin-stimulated conditions. While insightful, they do not necessarily reflect the physiology of the postprandial state. In addition, most studies do not examine aspects of glucose metabolism beyond the uptake process. Here we present an approach to study rodent muscle glucose and intermediary metabolism under the dynamic and physiologically relevant setting of the oral glucose tolerance test (OGTT). Methods and results: In vivo muscle glucose andmore » intermediary metabolism was investigated following oral administration of [U-{sup 13}C] glucose. Quadriceps muscles were collected 15 and 60 min after glucose administration and metabolite flux profiling was determined by measuring {sup 13}C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates via gas chromatography–mass spectrometry. While no dietary effects were noted in the glycolytic pathway, muscle from mice fed a high fat diet (HFD) exhibited a reduction in labelling in TCA intermediates. Interestingly, this appeared to be independent of alterations in flux through pyruvate dehydrogenase. In addition, our findings suggest that TCA cycle anaplerosis is negligible in muscle during an OGTT. Conclusions: Under the dynamic physiologically relevant conditions of the OGTT, skeletal muscle from HFD fed mice exhibits alterations in glucose metabolism at the level of the TCA cycle. - Highlights: • Dynamic metabolomics was used to investigate muscle glucose metabolism in vivo. • Mitochondrial TCA cycle metabolism is altered in muscle of HFD mice. • This defect was not pyruvate dehydrogenase mediated, as has been previously thought. • Mitochondrial TCA cycle anaplerosis in muscle is virtually absent during the OGTT.« less

A new reconstructive technique for posterior vaginal wall defects, a case report.

PubMed

Zetlitz, Elisabeth; Manook, Miriam; MacLeod, Alison; Hamilton, Stuart

2013-10-01

Post-partum vaginal laxity is a problem encountered by many women. More uncommon is a resulting vaginal defect. In most cases of laxity, a period of extensive physiotherapy can strengthen the pelvic muscles enough for symptoms to be minimized. However, this is not the case once there is a tissue defect. To present a new reconstructive method for patients with posterior vaginal wall defects. We present a case of a 38-year-old female who, 12 years prior to presentation, had a vaginal delivery. Due to complications during the delivery, she sustained pelvic trauma and developed a posterior vaginal wall defect. She had a sizable soft tissue defect, causing sexual, urinary, and confidence problems. Fat was harvested from the patient's abdomen and injected into the defect after more conservative treatment options were exhausted. The defect was corrected successfully using the minimally invasive Coleman fat grafting technique. This is to our knowledge the first case in the literature where a posterior vaginal defect has been corrected using Coleman fat grafting, and we believe that this treatment method may be of benefit to more patients. © 2013 International Society for Sexual Medicine.

Skeletal Muscle Tissue Engineering: Methods to Form Skeletal Myotubes and Their Applications

PubMed Central

Ostrovidov, Serge; Hosseini, Vahid; Ahadian, Samad; Fujie, Toshinori; Parthiban, Selvakumar Prakash; Ramalingam, Murugan; Bae, Hojae; Kaji, Hirokazu

2014-01-01

Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined. PMID:24320971

Inhibition of polyomavirus ori-dependent DNA replication by mSin3B.

PubMed

Xie, An-Yong; Folk, William R

2002-12-01

When tethered in cis to DNA, the transcriptional corepressor mSin3B inhibits polyomavirus (Py) ori-dependent DNA replication in vivo. Histone deacetylases (HDACs) appear not to be involved, since tethering class I and class II HDACs in cis does not inhibit replication and treating the cells with trichostatin A does not specifically relieve inhibition by mSin3B. However, the mSin3B L59P mutation that impairs mSin3B interaction with N-CoR/SMRT abrogates inhibition of replication, suggesting the involvement of N-CoR/SMRT. Py large T antigen interacts with mSin3B, suggesting an HDAC-independent mechanism by which mSin3B inhibits DNA replication.

A defect in the thymidine kinase 2 gene causing isolated mitochondrial myopathy without mtDNA depletion.

PubMed

Leshinsky-Silver, E; Michelson, M; Cohen, S; Ginsberg, M; Sadeh, M; Barash, V; Lerman-Sagie, T; Lev, D

2008-07-01

Isolated mitochondrial myopathies (IMM) are either due to primary defects in mtDNA, in nuclear genes that control mtDNA abundance and structure such as thymidine kinase 2 (TK2), or due to CoQ deficiency. Defects in the TK2 gene have been found to be associated with mtDNA depletion attributed to a depleted mitochondrial dNTP pool in non-dividing cells. We report an unusual case of IMM, homozygous for the H90N mutation in the TK2 gene but unlike other cases with the same mutation, does not demonstrate mtDNA depletion. The patient's clinical course is relatively mild and a muscle biopsy showed ragged red muscle fibers with a mild decrease in complexes I and an increase in complexes IV and II activities. This report extends the phenotypic expression of TK2 defects and suggests that all patients who present with an IMM even with normal quantities of mtDNA should be screened for TK2 mutations.

Chitin biological absorbable catheters bridging sural nerve grafts transplanted into sciatic nerve defects promote nerve regeneration.

PubMed

Wang, Zhi-Yong; Wang, Jian-Wei; Qin, Li-Hua; Zhang, Wei-Guang; Zhang, Pei-Xun; Jiang, Bao-Guo

2018-06-01

To investigate the efficacy of chitin biological absorbable catheters in a rat model of autologous nerve transplantation. A segment of sciatic nerve was removed to produce a sciatic nerve defect, and the sural nerve was cut from the ipsilateral leg and used as a graft to bridge the defect, with or without use of a chitin biological absorbable catheter surrounding the graft. The number and morphology of regenerating myelinated fibers, nerve conduction velocity, nerve function index, triceps surae muscle morphology, and sensory function were evaluated at 9 and 12 months after surgery. All of the above parameters were improved in rats in which the nerve graft was bridged with chitin biological absorbable catheters compared with rats without catheters. The results of this study indicate that use of chitin biological absorbable catheters to surround sural nerve grafts bridging sciatic nerve defects promotes recovery of structural, motor, and sensory function and improves muscle fiber morphology. © 2018 John Wiley & Sons Ltd.

[Applicability of Pedicled Coronoid Process and Temporal Muscle(Fascial)Combined(PCPTM)Flap for Reconstruction of Orbital Floor Defect Following Hemi-Maxillectomy for Advanced Maxillary Cancer - A Report of Two Cases].

PubMed

Karino, Masaaki; Kanno, Takahiro; Kaneko, Ichiro; Ide, Taichi; Yoshino, Aya; Sekine, Joji

2017-11-01

We usually perform surgery for resectable oral and maxillofacial carcinomas. Following complete cancer resection, reconstruction of soft and hard tissues using various types of local flaps and/or vascularized free flaps is usually performed. The maxilla is composed of various anatomical structures. In particular, reconstruction of the orbit is one of the most important and challenging procedures for prevention of functional and esthetic complications. Here we report 2 cases of orbital floor defect reconstruction following advanced maxillary cancer resection using a pedicled coronoid process and temporal muscle (fascial)combined(PCPTM)flap. Case 1: A 69-year-old Japanese man with squamous cell carcinoma of the left maxilla (cT4aN2bM0, Stage IV A). Case 2: An 86-year-old Japanese woman with recurrence of myoepithelial carcinoma of the left maxilla. In both cases, the orbital floor defect was reconstructed following hemi-maxillectomy using a PCPTM flap. Minor infection and/or partial necrosis were observed postoperatively, and a maxillofacial prosthesis was used in one case. A PCPTM flap was feasible for reconstruction of surgical defects of the orbital floor following maxillectomy for cancer.

The zebrafish dystrophic mutant softy maintains muscle fibre viability despite basement membrane rupture and muscle detachment

PubMed Central

Jacoby, Arie S.; Busch-Nentwich, Elisabeth; Bryson-Richardson, Robert J.; Hall, Thomas E.; Berger, Joachim; Berger, Silke; Sonntag, Carmen; Sachs, Caroline; Geisler, Robert; Stemple, Derek L.; Currie, Peter D.

2009-01-01

Summary The skeletal muscle basement membrane fulfils several crucial functions during development and in the mature myotome and defects in its composition underlie certain forms of muscular dystrophy. A major component of this extracellular structure is the laminin polymer, which assembles into a resilient meshwork that protects the sarcolemma during contraction. Here we describe a zebrafish mutant, softy, which displays severe embryonic muscle degeneration as a result of initial basement membrane failure. The softy phenotype is caused by a mutation in the lamb2 gene, identifying laminin β2 as an essential component of this basement membrane. Uniquely, softy homozygotes are able to recover and survive to adulthood despite the loss of myofibre adhesion. We identify the formation of ectopic, stable basement membrane attachments as a novel means by which detached fibres are able to maintain viability. This demonstration of a muscular dystrophy model possessing innate fibre viability following muscle detachment suggests basement membrane augmentation as a therapeutic strategy to inhibit myofibre loss. PMID:19736328

McNeil's Last Gasp: A Brief Post-Outburst Wind from V1647 Ori

NASA Astrophysics Data System (ADS)

Brittain, Sean D.; Simon, T.; Rettig, T. W.; Balsara, D.; Tilley, D.; Gibb, E.; Hinkle, K.; Troutman, M.

2007-05-01

We present new observations of the fundamental ro-vibrational CO spectra from V1647 Ori, the star whose recent outburst illuminated McNeil's Nebula. The spectra were acquired shortly after the luminosity of the source returned to its pre-outburst level (February 2006) and roughly one year later (December 2006 & February 2007). The CO lines evolved from centrally peaked emission lines during the outburst to P Cygni lines immediately following the outburst and back again to centrally peaked emission lines. We use a standard disk-magnetosphere interaction model to interpret the observations. The model predicts a decreasing truncation radius of the disk with increasing accretion rate. When the truncation radius of the disk moves radially inward or outward in response to changes in the accretion rate, the magnetic field must reorganize, leading to an enhanced reconnection rate. Such activity is expected to launch outflows, which have been observed at the onset and completion of the outburst of the system. We show that these trends are consistent with the fact that V1647 Ori produced a fast and hotter Hα outflow at the onset of the outburst whereas a slower, cooler CO outflow manifested itself as the system approached quiescence. This remarkable phenomenon provides further insight to how the disk and a stressed magnetosphere can generate disk driven winds. S.D.B. performed this work in part with support from the Michelson Fellowship Program. The data presented herein were obtained [in part] at the W.M. Keck Observatory and Gemini South Telescope. The Phoenix spectra were obtained as part of program GS-2006A-DD-1 and GS-2006B-DD-1.

Agonist mediated fetal muscle-type nicotinic acetylcholine receptor desensitization

USDA-ARS?s Scientific Manuscript database

The exposure of a developing embryo or fetus to teratogenic alkaloids from plants has the potential to cause developmental defects in livestock due to the inhibition of fetal movement by alkaloids. The mechanism behind the inhibition of fetal movement is the desensitization of fetal muscle-type nico...

Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration

PubMed Central

Shao, Hongwei; Xu, Qiyuan; Wu, Qiuling; Ma, Qi; Salgueiro, Luis; Wang, Jian’An; Eton, Darwin; Webster, Keith A; Yu, Hong

2011-01-01

The chemokine stromal cell-derived factor-1 (SDF-1) plays a critical role in mobilizing precursor cells in the bone marrow and is essential for efficient vascular regeneration and repair. We recently reported that calcium augments the expression of chemokine receptor CXCR4 and enhances the angiogenic potential of bone marrow derived cells (BMCs). Neovascularization is impaired by aging therefore we suggested that aging may cause defects of CXCR4 expression and cellular responses to calcium. Indeed we found that both the basal and calcium-induced surface expression of CXCR4 on BMCs was significantly reduced in 25-month-old mice compared with 2-month-old mice. Reduced Ca-induced CXCR4 expression in BMC from aged mice was associated with defective calcium influx. Diminished CXCR4 surface expression in BMC from aged mice correlated with diminished neovascularization in an ischemic hindlimb model with less accumulation of CD34+ progenitor cells in the ischemic muscle with or without local overexpression of SDF-1. Intravenous injection of BMCs from old mice homed less efficiently to ischemic muscle and stimulated significantly less neovascularization compared with the BMCs from young mice. Transplantation of old BMCs into young mice did not reconstitute CXCR4 functions suggesting that the defects were not reversible by changing the environment. We conclude that defects of basal and calcium-regulated functions of the CXCR4/SDF-1 axis in BMCs contribute significantly to the age-related loss of vasculogenic responses. PMID:21143386

Muscle fiber diameter assessment in cleft lip using image processing.

PubMed

Khan, M F J; Little, J; Abelli, L; Mossey, P A; Autelitano, L; Nag, T C; Rubini, M

2018-04-01

To pilot investigation of muscle fiber diameter (MFD) on medial and lateral sides of the cleft in 18 infants with cleft lip with or without cleft palate (CL/P) using image processing. Formalin-fixed paraffin-embedded (FFPE) tissue samples from the medial and lateral sides of the cleft were analyzed for MFD using an image-processing program (ImageJ). For within-case comparison, a paired Student's t test was performed. For comparisons between classes, an unpaired t test was used. Image processing enabled rapid measurement of MFD with majority of fibers showing diameter between 6 and 11 μm. There was no significant difference in mean MFD between the medial and lateral sides, or between CL and CLP. However, we found a significant difference on the medial side (p = .032) between males and females. The image processing on FFPE tissues resulted in easy quantification of MFD with finding of a smaller MFD on the medial side in males suggesting possible differences in orbicularis oris (OO) muscle between the two sexes in CL that warrants replication using larger number of cases. Moreover, this finding can aid subclinical phenotyping and potentially in the restoration of the anatomy and function of the upper lip. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Cadmium affects muscle type development and axon growth in zebrafish embryonic somitogenesis.

PubMed

Hen Chow, Elly Suk; Cheng, Shuk Han

2003-05-01

We have previously reported that exposure to cadmium during zebrafish embryonic development caused morphological malformations of organs and ectopic expression of genes involved in regulating developmental process. One of the most common developmental defects observed was altered axial curvature resulting from defects in the myotomes of the somites. In this study, we investigated the mechanisms of cadmium-induced toxicity in zebrafish somitogenesis. We showed that the critical period of exposure was the gastrulation period, which actually preceded the formation of the first morphologically distinct somites. The somites thus formed lost the typical chevron V-shape and are packed disorderly. The myogenic lineage commitment of the axial mesodermal cells was not affected, as the myogenic regulatory transcription factors were expressed normally. There were, however, losses of fast and slow muscle fibers in the myotomes. The innervation of the muscle blocks by spinal motoneurons is an important process of the somitogenesis. Both primary and secondary motoneurons appear to form normally while the axon growth is affected in cadmium-treated embryos. The notochord, which is essential in the patterning of the somites and the central nervous system, showed abnormal morphological features and failed to extend to the tail region. Taken together, it appears that cadmium exposure led to abnormal somite patterning of the muscle fibers and defects in axonogenesis.

Electrical stimulation as a biomimicry tool for regulating muscle cell behavior

PubMed Central

Ahadian, Samad; Ostrovidov, Serge; Hosseini, Vahid; Kaji, Hirokazu; Ramalingam, Murugan; Bae, Hojae; Khademhosseini, Ali

2013-01-01

There is a growing need to understand muscle cell behaviors and to engineer muscle tissues to replace defective tissues in the body. Despite a long history of the clinical use of electric fields for muscle tissues in vivo, electrical stimulation (ES) has recently gained significant attention as a powerful tool for regulating muscle cell behaviors in vitro. ES aims to mimic the electrical environment of electroactive muscle cells (e.g., cardiac or skeletal muscle cells) by helping to regulate cell-cell and cell-extracellular matrix (ECM) interactions. As a result, it can be used to enhance the alignment and differentiation of skeletal or cardiac muscle cells and to aid in engineering of functional muscle tissues. Additionally, ES can be used to control and monitor force generation and electrophysiological activity of muscle tissues for bio-actuation and drug-screening applications in a simple, high-throughput, and reproducible manner. In this review paper, we briefly describe the importance of ES in regulating muscle cell behaviors in vitro, as well as the major challenges and prospective potential associated with ES in the context of muscle tissue engineering. PMID:23823664

Electrical stimulation as a biomimicry tool for regulating muscle cell behavior.

PubMed

Ahadian, Samad; Ostrovidov, Serge; Hosseini, Vahid; Kaji, Hirokazu; Ramalingam, Murugan; Bae, Hojae; Khademhosseini, Ali

2013-01-01

There is a growing need to understand muscle cell behaviors and to engineer muscle tissues to replace defective tissues in the body. Despite a long history of the clinical use of electric fields for muscle tissues in vivo, electrical stimulation (ES) has recently gained significant attention as a powerful tool for regulating muscle cell behaviors in vitro. ES aims to mimic the electrical environment of electroactive muscle cells (e.g., cardiac or skeletal muscle cells) by helping to regulate cell-cell and cell-extracellular matrix (ECM) interactions. As a result, it can be used to enhance the alignment and differentiation of skeletal or cardiac muscle cells and to aid in engineering of functional muscle tissues. Additionally, ES can be used to control and monitor force generation and electrophysiological activity of muscle tissues for bio-actuation and drug-screening applications in a simple, high-throughput, and reproducible manner. In this review paper, we briefly describe the importance of ES in regulating muscle cell behaviors in vitro, as well as the major challenges and prospective potential associated with ES in the context of muscle tissue engineering.

Bioenergetics mechanisms regulating muscle stem cell self-renewal commitment and function.

PubMed

Abreu, Phablo

2018-04-16

Muscle stem cells or satellite cells are crucial for muscle maintenance and repair. These cells are mitotically quiescent and uniformly express the transcription factor Pax7, intermittently entering the cell cycle to give rise to daughter myogenic precursors cells and fuse with neighboring myofibers or self-renew, replenishing the stem cell pool in adult skeletal muscle. Pivotal roles of muscle stem cells in muscle repair have been uncovered, but it still remains unclear how muscle stem cell self-renewal is molecularly regulated and how muscle stem cells maintain muscle tissue homeostasis. Defects in muscle stem cell regulation to maintain/return to quiescence and self-renew are observed in degenerative conditions such as aging and neuromuscular disease. Recent works has suggested the existence of metabolic regulation and mitochondrial alterations in muscle stem cells, influencing the self-renewal commitment and function. Here I present a brief overview of recent understanding of how metabolic reprogramming governs self-renewal commitment, which is essential for conservation of muscle satellite cell pools throughout life, as well as the implications for regenerative medicine. Copyright © 2018. Published by Elsevier Masson SAS.

Deregulation of the Protocadherin Gene FAT1 Alters Muscle Shapes: Implications for the Pathogenesis of Facioscapulohumeral Dystrophy

PubMed Central

Caruso, Nathalie; Herberth, Balàzs; Bartoli, Marc; Puppo, Francesca; Dumonceaux, Julie; Zimmermann, Angela; Denadai, Simon; Lebossé, Marie; Roche, Stephane; Geng, Linda; Magdinier, Frederique; Attarian, Shahram; Bernard, Rafaelle; Maina, Flavio; Levy, Nicolas; Helmbacher, Françoise

2013-01-01

Generation of skeletal muscles with forms adapted to their function is essential for normal movement. Muscle shape is patterned by the coordinated polarity of collectively migrating myoblasts. Constitutive inactivation of the protocadherin gene Fat1 uncoupled individual myoblast polarity within chains, altering the shape of selective groups of muscles in the shoulder and face. These shape abnormalities were followed by early onset regionalised muscle defects in adult Fat1-deficient mice. Tissue-specific ablation of Fat1 driven by Pax3-cre reproduced muscle shape defects in limb but not face muscles, indicating a cell-autonomous contribution of Fat1 in migrating muscle precursors. Strikingly, the topography of muscle abnormalities caused by Fat1 loss-of-function resembles that of human patients with facioscapulohumeral dystrophy (FSHD). FAT1 lies near the critical locus involved in causing FSHD, and Fat1 mutant mice also show retinal vasculopathy, mimicking another symptom of FSHD, and showed abnormal inner ear patterning, predictive of deafness, reminiscent of another burden of FSHD. Muscle-specific reduction of FAT1 expression and promoter silencing was observed in foetal FSHD1 cases. CGH array-based studies identified deletion polymorphisms within a putative regulatory enhancer of FAT1, predictive of tissue-specific depletion of FAT1 expression, which preferentially segregate with FSHD. Our study identifies FAT1 as a critical determinant of muscle form, misregulation of which associates with FSHD. PMID:23785297

Functional recovery of completely denervated muscle: implications for innervation of tissue-engineered muscle.

PubMed

Kang, Sung-Bum; Olson, Jennifer L; Atala, Anthony; Yoo, James J

2012-09-01

Tissue-engineered muscle has been proposed as a solution to repair volumetric muscle defects and to restore muscle function. To achieve functional recovery, engineered muscle tissue requires integration of the host nerve. In this study, we investigated whether denervated muscle, which is analogous to tissue-engineered muscle tissue, can be reinnervated and can recover muscle function using an in vivo model of denervation followed by neurotization. The outcomes of this investigation may provide insights on the ability of tissue-engineered muscle to integrate with the host nerve and acquire normal muscle function. Eighty Lewis rats were classified into three groups: a normal control group (n=16); a denervated group in which sciatic innervations to the gastrocnemius muscle were disrupted (n=32); and a transplantation group in which the denervated gastrocnemius was repaired with a common peroneal nerve graft into the muscle (n=32). Neurofunctional behavior, including extensor postural thrust (EPT), withdrawal reflex latency (WRL), and compound muscle action potential (CMAP), as well as histological evaluations using alpha-bungarotoxin and anti-NF-200 were performed at 2, 4, 8, and 12 weeks (n=8) after surgery. We found that EPT was improved by transplantation of the nerve grafts, but the EPT values in the transplanted animals at 12 weeks postsurgery were still significantly lower than those measured for the normal control group at 4 weeks (EPT, 155.0±38.9 vs. 26.3±13.8 g, p<0.001; WRL, 2.7±2.30 vs. 8.3±5.5 s, p=0.027). In addition, CMAP latency and amplitude significantly improved with time after surgery in the transplantation group (p<0.001, one-way analysis of variance), and at 12 weeks postsurgery, CMAP latency and amplitude were not statistically different from normal control values (latency, 0.9±0.0 vs. 1.3±0.7 ms, p=0.164; amplitude, 30.2±7.0 vs. 46.4±26.9 mV, p=0.184). Histologically, regeneration of neuromuscular junctions was seen in the

Disruption of both nesprin 1 and desmin results in nuclear anchorage defects and fibrosis in skeletal muscle

PubMed Central

Chapman, Mark A.; Zhang, Jianlin; Banerjee, Indroneal; Guo, Ling T.; Zhang, Zhiwei; Shelton, G. Diane; Ouyang, Kunfu; Lieber, Richard L.; Chen, Ju

2014-01-01

Proper localization and anchorage of nuclei within skeletal muscle is critical for cellular function. Alterations in nuclear anchoring proteins modify a number of cellular functions including mechanotransduction, nuclear localization, chromatin positioning/compaction and overall organ function. In skeletal muscle, nesprin 1 and desmin are thought to link the nucleus to the cytoskeletal network. Thus, we hypothesize that both of these factors play a key role in skeletal muscle function. To examine this question, we utilized global ablation murine models of nesprin 1, desmin or both nesprin 1 and desmin. Herein, we have created the nesprin-desmin double-knockout (DKO) mouse, eliminating a major fraction of nuclear-cytoskeletal connections and enabling understanding of the importance of nuclear anchorage in skeletal muscle. Globally, DKO mice are marked by decreased lifespan, body weight and muscle strength. With regard to skeletal muscle, DKO myonuclear anchorage was dramatically decreased compared with wild-type, nesprin 1−/− and desmin−/− mice. Additionally, nuclear-cytoskeletal strain transmission was decreased in DKO skeletal muscle. Finally, loss of nuclear anchorage in DKO mice coincided with a fibrotic response as indicated by increased collagen and extracellular matrix deposition and increased passive mechanical properties of muscle bundles. Overall, our data demonstrate that nesprin 1 and desmin serve redundant roles in nuclear anchorage and that the loss of nuclear anchorage in skeletal muscle results in a pathological response characterized by increased tissue fibrosis and mechanical stiffness. PMID:24943590

Gamma-sarcoglycan is required for the response of archvillin to mechanical stimulation in skeletal muscle

PubMed Central

Spinazzola, Janelle M.; Smith, Tara C.; Liu, Min; Luna, Elizabeth J.; Barton, Elisabeth R.

2015-01-01

Loss of gamma-sarcoglycan (γ-SG) induces muscle degeneration and signaling defects in response to mechanical load, and its absence is common to both Duchenne and limb girdle muscular dystrophies. Growing evidence suggests that aberrant signaling contributes to the disease pathology; however, the mechanisms of γ-SG-mediated mechanical signaling are poorly understood. To uncover γ-SG signaling pathway components, we performed yeast two-hybrid screens and identified the muscle-specific protein archvillin as a γ-SG and dystrophin interacting protein. Archvillin protein and message levels were significantly upregulated at the sarcolemma of murine γ-SG-null (gsg−/−) muscle but delocalized in dystrophin-deficient mdx muscle. Similar elevation of archvillin protein was observed in human quadriceps muscle lacking γ-SG. Reintroduction of γ-SG in gsg−/− muscle by rAAV injection restored archvillin levels to that of control C57 muscle. In situ eccentric contraction of tibialis anterior (TA) muscles from C57 mice caused ERK1/2 phosphorylation, nuclear activation of P-ERK1/2 and stimulus-dependent archvillin association with P-ERK1/2. In contrast, TA muscles from gsg−/− and mdx mice exhibited heightened P-ERK1/2 and increased nuclear P-ERK1/2 localization following eccentric contractions, but the archvillin–P-ERK1/2 association was completely ablated. These results position archvillin as a mechanically sensitive component of the dystrophin complex and demonstrate that signaling defects caused by loss of γ-SG occur both at the sarcolemma and in the nucleus. PMID:25605665

Rehabilitation after cell transplantation for cartilage defects.

PubMed

Deszczynski, J; Slynarski, K

2006-01-01

Rehabilitation is a key element of successful treatment of cartilage defects with cell transplantation. The process of graft maturation takes approximately 18 months and cannot be accelerated, but requires carefully introduced steps leading to early recovery of joint function. Rehabilitation starts at 8 hours after surgery with the continuous passive motion (CPM) exercises and physiotherapy. For the first 6 weeks, patients continue with CPM in the range of 0 degrees to 45 degrees for femoral and tibial defects and 0 degrees to 30 degrees for patellofemoral joint reconstruction. Isometric muscle training and scar manual therapy are introduced. Patients are allowed to weight-bear as tolerated from the second week after surgery. After this initial phase, from 6 to 8 weeks after surgery, rehabilitation is accelerated with increased load-bearing and progressive range of motion to full flexion. Usually patients are able to walk without crutches in this time. Proprioceptive training is introduced with the advance of pain-free full range of motion and no discomfort with full weight-bearing. At 6 months after surgery, most patients recover joint function, making it possible for them to return to daily living activities. However, they need to continue with muscle, proprioceptive, and sports-specific rehabilitation exercises. The rehabilitation process is complicated, requiring close cooperation between the patient and surgeon-physiotherapist team to understand the symptoms and address them in a timely fashion.

The Trapezius Muscle Flap: A Viable Alternative for Posterior Scalp and Neck Reconstruction.

PubMed

Yang, Hee Jun; Lee, Dong Hun; Kim, Yang Woo; Lee, Sang Gu; Cheon, Young Woo

2016-11-01

The trapezius muscle flap is not usually the first reconstructive option for skin and soft tissue defects in the posterior neck and scalp due to surgeons' unfamiliarity with the surgical anatomy and developments in free tissue transfer techniques. The goals of this study were to describe the clinical use of trapezius flaps in posterior neck and scalp reconstruction, and to investigate the vascular anatomy of trapezius flaps in Asians in order to obtain information facilitating the safe design and elevation of flaps in which most of the muscle is preserved. A retrospective chart review was performed of 10 patients who underwent trapezius muscle flap for posterior neck and scalp defects. We also performed an anatomical study of 16 flaps harvested from 8 preserved Asian adult cadavers and evaluated the main landmarks relevant for trapezius muscle flap. In the anatomical study, the mean vertical height from the inferior angle of the scapula to the point at which the superficial cervical artery penetrated the trapezius was 4.31±2.14 cm. The mean vertical height of the trapezius muscle flap pivot point was 9.53±2.08 cm from the external occipital protuberance. Among the 10 flaps, partial necrosis on the overlaid skin graft occurred in 1 patient and postoperative seroma occurred in another patient. Vascular variations in the trapezius muscle flap are uncommon in Asians, but when present, such variations appear to have little impact on harvesting the flap or on its circulation. The trapezius muscle flap is a viable alternative for posterior neck and scalp reconstruction.

Subacute reconstruction of lower leg and foot defects due to high velocity-high energy injuries caused by gunshots, missiles, and land mines.

PubMed

Celiköz, Bahattin; Sengezer, Mustafa; Işik, Selçuk; Türegün, Murat; Deveci, Mustafa; Duman, Haluk; Acikel, Cengiz; Nişanci, Mustafa; Oztürk, Serdar

2005-01-01

The present study reviews 215 male patients suffering high velocity-high energy injuries of the lower leg or foot caused by war weapons such as missiles, gunshots, and land mines. They were treated in the Department of Plastic and Reconstructive Surgery at Gulhane Military Medical Academy (Ankara, Turkey) between November 1993-January 2001. Severe soft-tissue defects requiring flap coverage and associated open bone fractures that were treated 7-21 days (mean, 9.6 days) after the injury were included in the study. Twenty-three of 226 extremities (10.2%) underwent primary below-knee amputation. The number of debridements prior to definitive treatment was between 1-3 (mean, 1.9). Gustilo type III open tibia fractures accompanied 104 of 126 soft-tissue defects of the lower leg. Sixty-four bone defects accompanied 83 soft-tissue defects of the feet. Eighteen local pedicled muscle flaps and 208 free muscle flaps (latissimus dorsi, rectus abdominis, and gracilis) were used in soft-tissue coverage of 209 defects. Overall, the free muscle flap success rate was 91.3%. Bone defects were restored with 106 bone grafts, 25 free fibula flaps, and 14 distraction osteogenesis procedures. Osseous and soft-tissue defects were reconstructed simultaneously at the first definitive treatment in 94% of cases. The mean follow-up after definitive treatment was 25 (range, 9-47) months. The average full weight-bearing times for lower leg and feet injuries were 8.4 months and 4 months, respectively. Early, aggressive, and serial debridement of osseous and soft tissue, early restoration of bone and soft-tissue defects at the same stage, intensive rehabilitation, and patient education were the key points in the management of high velocity-high energy injuries of the lower leg and foot. copyright 2005 Wiley-Liss, Inc.

Comparison of metamotivational dominance and cultural identity between Japanese National Team and Māori All Blacks rugby players.

PubMed

Kuroda, Yusuke; Palmer, Farah; Nakazawa, Makoto

2017-11-01

This pilot study used a reversal theory framework to examine metamotivational dominance of rugby players on the Māori All Blacks (MABs) squad of New Zealand and the Japanese National Team (JNT). Since the two groups have different cultural team demographics, cultural identity was also examined. Twenty six players from the MABs and 31 from the JNT completed questionnaires on metamotivational dominance and cultural identity. In terms of metamotivational dominance, the findings indicated that the MABs were more playful minded and spontaneous oriented than the JNT. Regarding cultural identity, the JNT showed a greater knowledge of their own culture and higher comfort level in their cultural context, while the MABs felt more positive and willing to sustain their own culture. The motivational personality differences between the teams may reflect the style of play that is valued within each team culture that is, flair, spontaneity and high-risk play within Māori rugby, and structure, team unity and conformity within the JNT. This suggests that metamotivational dominance of teams and players is influenced by the cultural identity of both the individuals and the group, which may have a further impact on team cohesion and performance.

Synergizing Engineering and Biology to Treat and Model Skeletal Muscle Injury and Disease

PubMed Central

Bursac, Nenad; Juhas, Mark; Rando, Thomas A.

2016-01-01

Although skeletal muscle is one of the most regenerative organs in our body, various genetic defects, alterations in extrinsic signaling, or substantial tissue damage can impair muscle function and the capacity for self-repair. The diversity and complexity of muscle disorders have attracted much interest from both cell biologists and, more recently, bioengineers, leading to concentrated efforts to better understand muscle pathology and develop more efficient therapies. This review describes the biological underpinnings of muscle development, repair, and disease, and discusses recent bioengineering efforts to design and control myomimetic environments, both to study muscle biology and function and to aid in the development of new drug, cell, and gene therapies for muscle disorders. The synergy between engineering-aided biological discovery and biology-inspired engineering solutions will be the path forward for translating laboratory results into clinical practice. PMID:26643021

Immediate reconstruction of mandibular defects with a composite sternocleidomastoid musculoclavicular graft

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barnes, D.R.; Ossoff, R.H.; Pecaro, B.

1981-01-01

The problem of mandibular reconstruction has been approached using many surgical techniques. This article studies one such approach--reconstruction using full-thickness clavicle pedicled on the sternocleidomastoid muscle. Five patients with stage II and stage III carcinoma of the anterior part of the floor of the mouth were treated with mandibular resection and neck dissection. The resulting defects were immediately reconstructed with the clavicle-sternocleidomastoid muscle technique. The patients were observed from one to three years and were examined postoperatively with technetium Tc 99m medronate scans, which demonstrated the grafts to be viable. The technique proved reliable in a limited clinical trial.

Hypoglossal-facial nerve reconstruction using a Y-tube-conduit reduces aberrant synkinetic movements of the orbicularis oculi and vibrissal muscles in rats.

PubMed

Kaya, Yasemin; Ozsoy, Umut; Turhan, Murat; Angelov, Doychin N; Sarikcioglu, Levent

2014-01-01

The facial nerve is the most frequently damaged nerve in head and neck trauma. Patients undergoing facial nerve reconstruction often complain about disturbing abnormal synkinetic movements of the facial muscles (mass movements, synkinesis) which are thought to result from misguided collateral branching of regenerating motor axons and reinnervation of inappropriate muscles. Here, we examined whether use of an aorta Y-tube conduit during reconstructive surgery after facial nerve injury reduces synkinesis of orbicularis oris (blink reflex) and vibrissal (whisking) musculature. The abdominal aorta plus its bifurcation was harvested (N = 12) for Y-tube conduits. Animal groups comprised intact animals (Group 1), those receiving hypoglossal-facial nerve end-to-end coaptation alone (HFA; Group 2), and those receiving hypoglossal-facial nerve reconstruction using a Y-tube (HFA-Y-tube, Group 3). Videotape motion analysis at 4 months showed that HFA-Y-tube group showed a reduced synkinesis of eyelid and whisker movements compared to HFA alone.

Hypoglossal-Facial Nerve Reconstruction Using a Y-Tube-Conduit Reduces Aberrant Synkinetic Movements of the Orbicularis Oculi and Vibrissal Muscles in Rats

PubMed Central

Kaya, Yasemin; Ozsoy, Umut; Turhan, Murat; Angelov, Doychin N.; Sarikcioglu, Levent

2014-01-01

The facial nerve is the most frequently damaged nerve in head and neck trauma. Patients undergoing facial nerve reconstruction often complain about disturbing abnormal synkinetic movements of the facial muscles (mass movements, synkinesis) which are thought to result from misguided collateral branching of regenerating motor axons and reinnervation of inappropriate muscles. Here, we examined whether use of an aorta Y-tube conduit during reconstructive surgery after facial nerve injury reduces synkinesis of orbicularis oris (blink reflex) and vibrissal (whisking) musculature. The abdominal aorta plus its bifurcation was harvested (N = 12) for Y-tube conduits. Animal groups comprised intact animals (Group 1), those receiving hypoglossal-facial nerve end-to-end coaptation alone (HFA; Group 2), and those receiving hypoglossal-facial nerve reconstruction using a Y-tube (HFA-Y-tube, Group 3). Videotape motion analysis at 4 months showed that HFA-Y-tube group showed a reduced synkinesis of eyelid and whisker movements compared to HFA alone. PMID:25574468

A qualitative analysis of Māori and Pacific smokers' views on informed choice and smoking

PubMed Central

Gifford, Heather; Tautolo, El-Shadan; Erick, Stephanie; Hoek, Janet; Gray, Rebecca; Edwards, Richard

2016-01-01

Objectives Tobacco companies frame smoking as an informed choice, a strategy that holds individuals responsible for harms they incur. Few studies have tested this argument, and even fewer have examined how informed indigenous smokers or those from minority ethnicities are when they start smoking. We explored how young adult Māori and Pacific smokers interpreted ‘informed choice’ in relation to smoking. Participants Using recruitment via advertising, existing networks and word of mouth, we recruited and undertook qualitative in-depth interviews with 20 Māori and Pacific young adults aged 18–26 years who smoked. Analyses Data were analysed using an informed-choice framework developed by Chapman and Liberman. We used a thematic analysis approach to identify themes that extended this framework. Results Few participants considered themselves well informed and none met more than the framework's initial two criteria. Most reflected on their unthinking uptake and subsequent addiction, and identified environmental factors that had facilitated uptake. Nonetheless, despite this context, most agreed that they had made an informed choice to smoke. Conclusions The discrepancy between participants' reported knowledge and understanding of smoking's risks, and their assessment of smoking as an informed choice, reflects their view of smoking as a symbol of adulthood. Policies that make tobacco more difficult to use in social settings could help change social norms around smoking and the ease with which initiation and addiction currently occur. PMID:27188813

Defective mitochondrial dynamics is an early event in skeletal muscle of an amyotrophic lateral sclerosis mouse model.

PubMed

Luo, Guo; Yi, Jianxun; Ma, Changling; Xiao, Yajuan; Yi, Frank; Yu, Tian; Zhou, Jingsong

2013-01-01

Mitochondria are dynamic organelles that constantly undergo fusion and fission to maintain their normal functionality. Impairment of mitochondrial dynamics is implicated in various neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is an adult-onset neuromuscular degenerative disorder characterized by motor neuron death and muscle atrophy. ALS onset and progression clearly involve motor neuron degeneration but accumulating evidence suggests primary muscle pathology may also be involved. Here, we examined mitochondrial dynamics in live skeletal muscle of an ALS mouse model (G93A) harboring a superoxide dismutase mutation (SOD1(G93A)). Using confocal microscopy combined with overexpression of mitochondria-targeted photoactivatable fluorescent proteins, we discovered abnormal mitochondrial dynamics in skeletal muscle of young G93A mice before disease onset. We further demonstrated that similar abnormalities in mitochondrial dynamics were induced by overexpression of mutant SOD1(G93A) in skeletal muscle of normal mice, indicating the SOD1 mutation drives ALS-like muscle pathology in the absence of motor neuron degeneration. Mutant SOD1(G93A) forms aggregates inside muscle mitochondria and leads to fragmentation of the mitochondrial network as well as mitochondrial depolarization. Partial depolarization of mitochondrial membrane potential in normal muscle by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) caused abnormalities in mitochondrial dynamics similar to that in the SOD1(G93A) model muscle. A specific mitochondrial fission inhibitor (Mdivi-1) reversed the SOD1(G93A) action on mitochondrial dynamics, indicating SOD1(G93A) likely promotes mitochondrial fission process. Our results suggest that accumulation of mutant SOD1(G93A) inside mitochondria, depolarization of mitochondrial membrane potential and abnormal mitochondrial dynamics are causally linked and cause intrinsic muscle pathology, which occurs early in the course of ALS and may

Lethality of Sortase Depletion in Actinomyces oris Caused by Excessive Membrane Accumulation of a Surface Glycoprotein

PubMed Central

Wu, Chenggang; Huang, I-Hsiu; Chang, Chungyu; Reardon-Robinson, Melissa Elizabeth; Das, Asis; Ton-That, Hung

2014-01-01

Sortase, a cysteine-transpeptidase conserved in Gram-positive bacteria, anchors on the cell wall many surface proteins that facilitate bacterial pathogenesis and fitness. Genetic disruption of the housekeeping sortase in several Gram-positive pathogens reported thus far attenuates virulence, but not bacterial growth. Paradoxically, we discovered that depletion of the housekeeping sortase SrtA was lethal for Actinomyces oris; yet, all of its predicted cell wall-anchored protein substrates (AcaA-N) were individually dispensable for cell viability. Using Tn5-transposon mutagenesis to identify factors that upend lethality of srtA deletion, we uncovered a set of genetic suppressors harboring transposon insertions within genes of a locus encoding AcaC and a LytR-CpsA-Psr (LCP)-like protein. AcaC was shown to be highly glycosylated and dependent on LCP for its glycosylation. Upon SrtA depletion, the glycosylated form of AcaC, hereby renamed GspA, was accumulated in the membrane. Overexpression of GspA in a mutant lacking gspA and srtA was lethal; conversely, cells overexpressing a GspA mutant missing a membrane-localization domain were viable. The results reveal a unique glycosylation pathway in A. oris that is coupled to cell wall anchoring catalyzed by sortase SrtA. Significantly, this novel phenomenon of glyco-stress provides convenient cell-based assays for developing a new class of inhibitors against Gram-positive pathogens. PMID:25230351

Disruption of both nesprin 1 and desmin results in nuclear anchorage defects and fibrosis in skeletal muscle.

PubMed

Chapman, Mark A; Zhang, Jianlin; Banerjee, Indroneal; Guo, Ling T; Zhang, Zhiwei; Shelton, G Diane; Ouyang, Kunfu; Lieber, Richard L; Chen, Ju

2014-11-15

Proper localization and anchorage of nuclei within skeletal muscle is critical for cellular function. Alterations in nuclear anchoring proteins modify a number of cellular functions including mechanotransduction, nuclear localization, chromatin positioning/compaction and overall organ function. In skeletal muscle, nesprin 1 and desmin are thought to link the nucleus to the cytoskeletal network. Thus, we hypothesize that both of these factors play a key role in skeletal muscle function. To examine this question, we utilized global ablation murine models of nesprin 1, desmin or both nesprin 1 and desmin. Herein, we have created the nesprin-desmin double-knockout (DKO) mouse, eliminating a major fraction of nuclear-cytoskeletal connections and enabling understanding of the importance of nuclear anchorage in skeletal muscle. Globally, DKO mice are marked by decreased lifespan, body weight and muscle strength. With regard to skeletal muscle, DKO myonuclear anchorage was dramatically decreased compared with wild-type, nesprin 1(-/-) and desmin(-/-) mice. Additionally, nuclear-cytoskeletal strain transmission was decreased in DKO skeletal muscle. Finally, loss of nuclear anchorage in DKO mice coincided with a fibrotic response as indicated by increased collagen and extracellular matrix deposition and increased passive mechanical properties of muscle bundles. Overall, our data demonstrate that nesprin 1 and desmin serve redundant roles in nuclear anchorage and that the loss of nuclear anchorage in skeletal muscle results in a pathological response characterized by increased tissue fibrosis and mechanical stiffness. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Proximity of Ribosomal Protein Genes to oriC Enhances Vibrio cholerae Fitness in the Absence of Multifork Replication.

PubMed

Soler-Bistué, Alfonso; Timmermans, Michaël; Mazel, Didier

2017-02-28

Recent works suggest that bacterial gene order links chromosome structure to cell homeostasis. Comparative genomics showed that, in fast-growing bacteria, ribosomal protein genes (RP) locate near the replication origin ( oriC ). We recently showed that Vibrio cholerae employs this positional bias as a growth optimization strategy: under fast-growth conditions, multifork replication increases RP dosage and expression. However, RP location may provide advantages in a dosage-independent manner: for example, the physical proximity of the many ribosomal components, in the context of a crowded cytoplasm, may favor ribosome biogenesis. To uncover putative dosage-independent effects, we studied isogenic V. cholerae derivatives in which the major RP locus, S10-spc-α (S10), was relocated to alternative genomic positions. When bacteria grew fast, bacterial fitness was reduced according to the S10 relative distance to oriC The growth of wild-type V. cholerae could not be improved by additional copies of the locus, suggesting a physiologically optimized genomic location. Slow growth is expected to uncouple RP position from dosage, since multifork replication does not occur. Under these conditions, we detected a fitness impairment when S10 was far from oriC Deep sequencing followed by marker frequency analysis in the absence of multifork replication revealed an up to 30% S10 dosage reduction associated with its relocation that closely correlated with fitness alterations. Hence, the impact of S10 location goes beyond a growth optimization strategy during feast periods. RP location may be important during the whole life cycle of this pathogen. IMPORTANCE The role of gene order within the bacterial chromosome is poorly understood. In fast growers, the location of genes linked with the expression of genetic information (i.e., transcription and translation) is biased toward oriC It was proposed that the location of these genes helps to maximize their expression by recruiting

Poorly Understood Aspects of Striated Muscle Contraction

PubMed Central

Månsson, Alf

2015-01-01

Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs. PMID:25961006

Poorly understood aspects of striated muscle contraction.

PubMed

Månsson, Alf; Rassier, Dilson; Tsiavaliaris, Georgios

2015-01-01

Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs.

How to minimize ischemic complication related to swollen temporalis muscle following indirect revascularization surgery in moyamoya disease: a technical report.

PubMed

Joo, Sung Pil; Kim, Tae Sun; Moon, Hyung Sik

2014-05-01

There are several reports in the literature of postoperative ischemic events due to swelling of the temporalis muscle after indirect revascularization surgery. Here, we report our surgical technique for preventing ischemic events during the acute postoperative recovery period in moyamoya patients. We used various types of titanium mesh to cover the bony defect area in 8 patients (10 operations) with moyamoya disease. The mesh was cut and manipulated according to the shape of the bony defect. Surgical results were favorable, with no newly developed ischemic event or infarction in the acute recovery period. The mesh formed an outer table of skull, so there was no compressive effect on the temporalis muscle and no cosmetic defects. The titanium mesh appears to be effective and useful for prevention of ischemic insult in the treatment of moyamoya disease. The choice of this procedure depends on both the operative findings of temporalis muscle thickness and the status of ischemic vulnerability of moyamoya brain. Georg Thieme Verlag KG Stuttgart · New York.

The ALMA early science view of FUor/EXor objects - I. Through the looking-glass of V2775 Ori

NASA Astrophysics Data System (ADS)

Zurlo, Alice; Cieza, Lucas A.; Williams, Jonathan P.; Canovas, Hector; Perez, Sebastian; Hales, Antonio; Mužić, Koraljka; Principe, David A.; Ruíz-Rodríguez, Dary; Tobin, John; Zhang, Yichen; Zhu, Zhaohuan; Casassus, Simon; Prieto, Jose L.

2017-02-01

As part of an Atacama Large Millimeter/submillimiter Array (ALMA) survey to study the origin of episodic accretion in young eruptive variables, we have observed the circum-stellar environment of the star V2775 Ori. This object is a very young, pre-main sequence object which displays a large amplitude outburst characteristic of the FUor class. We present Cycle-2 band 6 observations of V2775 Ori with a continuum and CO (2-1) isotopologue resolution of 0.25 arcsec (103 au). We report the detection of a marginally resolved circum-stellar disc in the ALMA continuum with an integrated flux of 106 ± 2 mJy, characteristic radius of ˜30 au, inclination of 14.0^{+7.8}_{-14.5} deg and is oriented nearly face-on with respect to the plane of the sky. The 12CO emission is separated into distinct blue and redshifted regions that appear to be rings or shells of expanding material from quasi-episodic outbursts. The system is oriented in such a way that the disc is seen through the outflow remnant of V2775 Ori, which has an axis along our line of sight. The 13CO emission displays similar structure to that of the 12CO, while the C18O line emission is very weak. We calculated the expansion velocities of the low- and medium-density material with respect to the disc to be of -2.85 (blue), 4.4 (red) and -1.35 and 1.15 km s-1 (for blue and red) and we derived the mass, momentum and kinetic energy of the expanding gas. The outflow has an hourglass shape where the cavities are not seen. We interpret the shapes that the gas traces as cavities excavated by an ancient outflow. We report a detection of line emission from the circumstellar disc and derive a lower limit of the gas mass of 3 MJup.

Skeletal Muscle Pathophysiology: The Emerging Role of Spermine Oxidase and Spermidine.

PubMed

Cervelli, Manuela; Leonetti, Alessia; Duranti, Guglielmo; Sabatini, Stefania; Ceci, Roberta; Mariottini, Paolo

2018-02-14

Skeletal muscle comprises approximately 40% of the total body mass. Preserving muscle health and function is essential for the entire body in order to counteract chronic diseases such as type II diabetes, cardiovascular diseases, and cancer. Prolonged physical inactivity, particularly among the elderly, causes muscle atrophy, a pathological state with adverse outcomes such as poor quality of life, physical disability, and high mortality. In murine skeletal muscle C2C12 cells, increased expression of the spermine oxidase (SMOX) enzyme has been found during cell differentiation. Notably, SMOX overexpression increases muscle fiber size, while SMOX reduction was enough to induce muscle atrophy in multiple murine models. Of note, the SMOX reaction product spermidine appears to be involved in skeletal muscle atrophy/hypertrophy. It is effective in reactivating autophagy, ameliorating the myopathic defects of collagen VI-null mice. Moreover, spermidine treatment, if combined with exercise, can affect D-gal-induced aging-related skeletal muscle atrophy. This review hypothesizes a role for SMOX during skeletal muscle differentiation and outlines its role and that of spermidine in muscle atrophy. The identification of new molecular pathways involved in the maintenance of skeletal muscle health could be beneficial in developing novel therapeutic lead compounds to treat muscle atrophy.

Skeletal Muscle Pathophysiology: The Emerging Role of Spermine Oxidase and Spermidine

PubMed Central

Duranti, Guglielmo; Sabatini, Stefania; Ceci, Roberta; Mariottini, Paolo

2018-01-01

Skeletal muscle comprises approximately 40% of the total body mass. Preserving muscle health and function is essential for the entire body in order to counteract chronic diseases such as type II diabetes, cardiovascular diseases, and cancer. Prolonged physical inactivity, particularly among the elderly, causes muscle atrophy, a pathological state with adverse outcomes such as poor quality of life, physical disability, and high mortality. In murine skeletal muscle C2C12 cells, increased expression of the spermine oxidase (SMOX) enzyme has been found during cell differentiation. Notably, SMOX overexpression increases muscle fiber size, while SMOX reduction was enough to induce muscle atrophy in multiple murine models. Of note, the SMOX reaction product spermidine appears to be involved in skeletal muscle atrophy/hypertrophy. It is effective in reactivating autophagy, ameliorating the myopathic defects of collagen VI-null mice. Moreover, spermidine treatment, if combined with exercise, can affect D-gal-induced aging-related skeletal muscle atrophy. This review hypothesizes a role for SMOX during skeletal muscle differentiation and outlines its role and that of spermidine in muscle atrophy. The identification of new molecular pathways involved in the maintenance of skeletal muscle health could be beneficial in developing novel therapeutic lead compounds to treat muscle atrophy. PMID:29443878

Proteomic approach to characterize biochemistry of meat quality defects.

PubMed

Schilling, M W; Suman, S P; Zhang, X; Nair, M N; Desai, M A; Cai, K; Ciaramella, M A; Allen, P J

2017-10-01

Proteomics can be used to characterize quality defects including pale, soft, and exudative (PSE) meat (pork and poultry), woody broiler breast meat, reddish catfish fillets, meat toughness, and beef myoglobin oxidation. PSE broiler meat was characterized by 15 proteins that differed in abundance in comparison to normal broiler breast meat, and eight proteins were differentially expressed in woody breast meat in comparison to normal breast meat. Hemoglobin was the only protein that was differentially expressed between red and normal catfish fillets. However, inducing low oxygen and/or heat stress conditions to catfish fillets did not lead to the production of red fillets. Proteomic data provided information pertaining to the protein differences that exist in meat quality defects. However, these data need to be evaluated in conjunction with information pertaining to genetics, nutrition, environment of the live animal, muscle to meat conversion, meat quality analyses and sensory attributes to understand causality, protein biomarkers, and ultimately how to prevent quality defects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glucose uptake and glycogen synthesis in muscles from immobilized limbs

NASA Technical Reports Server (NTRS)

Nicholson, W. F.; Watson, P. A.; Booth, F. W.

1984-01-01

Defects in glucose metabolism in muscles of immobilized limbs of mice were related to alterations in insulin binding, insulin responsiveness, glucose supply, and insulin activation of glycogen synthase. These were tested by in vitro methodology. A significant lessening in the insulin-induced maximal response of 2-deoxyglucose uptake into the mouse soleus muscle occurred between the 3rd and 8th h of limb immobilization, suggesting a decreased insulin responsiveness. Lack of change in the specific binding of insulin to muscles of 24-h immobilized limbs indicates that a change in insulin receptor number did not play a role in the failure of insulin to stimulate glucose metabolism. Its inability to stimulate glycogen synthesis in muscle from immobilized limbs is due, in part, to a lack of glucose supply to glycogen synthesis and also to the ineffectiveness of insulin to increase the percentage of glycogen synthase in its active form in muscles from 24-h immobilized limbs.

Regenerative capacity of mdx mouse muscles after repeated applications of myo-necrotic bupivacaine.

PubMed

Itagaki, Y; Saida, K; Iwamura, K

1995-01-01

We injected bupivacaine (BPVC), which produces muscle fiber necrosis, repeatedly into the soleus muscles of mdx mice, which represent a model of human Duchenne muscular dystrophy, over a 12-month period. Cytological and morphometric analysis revealed that the regenerative capacity of repeatedly BPVC-injected mdx muscles was almost equal to that of the saline-injected mdx muscles. At 9 months of age the endomysial collagen content of mdx muscles was 4.6 times that of control mice muscles, and was 7.2 times that of control mice muscle at 12 months. These results suggest that the regenerative capacity of the mdx muscle is quite large and that myo-necrosis induced by an extrinsic cause, such as BPVC, may not be an important factor in the disease progress. However, endomysial collagen, for which the mechanism of increase may be related to the defect of dystrophin, may play an important role in gradual decline of regeneration.

Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS.

PubMed

Brown, Audrey E; Dibnah, Beth; Fisher, Emily; Newton, Julia L; Walker, Mark

2018-06-29

Skeletal muscle fatigue and post-exertional malaise are key symptoms of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (ME/CFS). We have previously shown that AMP-activated protein kinase (AMPK) activation and glucose uptake are impaired in primary human skeletal muscle cell cultures derived from patients with ME/CFS in response to electrical pulse stimulation (EPS), a method which induces contraction of muscle cells in vitro The aim of the present study was to assess if AMPK could be activated pharmacologically in ME/CFS. Primary skeletal muscle cell cultures from patients with ME/CFS and healthy controls were treated with either metformin or compound 991. AMPK activation was assessed by Western blot and glucose uptake measured. Both metformin and 991 treatment significantly increased AMPK activation and glucose uptake in muscle cell cultures from both controls and ME/CFS. Cellular ATP content was unaffected by treatment although ATP content was significantly decreased in ME/CFS compared with controls. Pharmacological activation of AMPK can improve glucose uptake in muscle cell cultures from patients with ME/CFS. This suggests that the failure of EPS to activate AMPK in these muscle cultures is due to a defect proximal to AMPK. Further work is required to delineate the defect and determine whether pharmacological activation of AMPK improves muscle function in patients with ME/CFS. © 2018 The Author(s).

TGFβ regulates epithelial-mesenchymal interactions through WNT signaling activity to control muscle development in the soft palate.

PubMed

Iwata, Jun-ichi; Suzuki, Akiko; Yokota, Toshiaki; Ho, Thach-Vu; Pelikan, Richard; Urata, Mark; Sanchez-Lara, Pedro A; Chai, Yang

2014-02-01

Clefting of the soft palate occurs as a congenital defect in humans and adversely affects the physiological function of the palate. However, the molecular and cellular mechanism of clefting of the soft palate remains unclear because few animal models exhibit an isolated cleft in the soft palate. Using three-dimensional microCT images and histological reconstruction, we found that loss of TGFβ signaling in the palatal epithelium led to soft palate muscle defects in Tgfbr2(fl/fl);K14-Cre mice. Specifically, muscle mass was decreased in the soft palates of Tgfbr2 mutant mice, following defects in cell proliferation and differentiation. Gene expression of Dickkopf (Dkk1 and Dkk4), negative regulators of WNT-β-catenin signaling, is upregulated in the soft palate of Tgfbr2(fl/fl);K14-Cre mice, and WNT-β-catenin signaling is disrupted in the palatal mesenchyme. Importantly, blocking the function of DKK1 and DKK4 rescued the cell proliferation and differentiation defects in the soft palate of Tgfbr2(fl/fl);K14-Cre mice. Thus, our findings indicate that loss of TGFβ signaling in epithelial cells compromises activation of WNT signaling and proper muscle development in the soft palate through tissue-tissue interactions, resulting in a cleft soft palate. This information has important implications for prevention and non-surgical correction of cleft soft palate.

The Trapezius Muscle Flap: A Viable Alternative for Posterior Scalp and Neck Reconstruction

PubMed Central

Yang, Hee Jun; Kim, Yang Woo; Lee, Sang Gu

2016-01-01

Background The trapezius muscle flap is not usually the first reconstructive option for skin and soft tissue defects in the posterior neck and scalp due to surgeons' unfamiliarity with the surgical anatomy and developments in free tissue transfer techniques. The goals of this study were to describe the clinical use of trapezius flaps in posterior neck and scalp reconstruction, and to investigate the vascular anatomy of trapezius flaps in Asians in order to obtain information facilitating the safe design and elevation of flaps in which most of the muscle is preserved. Methods A retrospective chart review was performed of 10 patients who underwent trapezius muscle flap for posterior neck and scalp defects. We also performed an anatomical study of 16 flaps harvested from 8 preserved Asian adult cadavers and evaluated the main landmarks relevant for trapezius muscle flap. Results In the anatomical study, the mean vertical height from the inferior angle of the scapula to the point at which the superficial cervical artery penetrated the trapezius was 4.31±2.14 cm. The mean vertical height of the trapezius muscle flap pivot point was 9.53±2.08 cm from the external occipital protuberance. Among the 10 flaps, partial necrosis on the overlaid skin graft occurred in 1 patient and postoperative seroma occurred in another patient. Conclusions Vascular variations in the trapezius muscle flap are uncommon in Asians, but when present, such variations appear to have little impact on harvesting the flap or on its circulation. The trapezius muscle flap is a viable alternative for posterior neck and scalp reconstruction. PMID:27896183

Toxicity and developmental defects of different sizes and shape nickel nanoparticles in zebrafish

PubMed Central

Ispas, Cristina; Andreescu, Daniel; Patel, Avni; Goia, Dan V.; Andreescu, Silvana; Wallace, Kenneth N.

2009-01-01

Metallic nanoparticles such as nickel are used in catalytic, sensing and electronic applications, but health and environmental affects have not been fully investigated. While some metal nanoparticles result in toxicity, it is also important to determine whether nanoparticles of the same metal but of different size and shape changes toxicity. Three different size nickel nanoparticle (Ni NPs) of 30, 60, and 100 nm and larger particle clusters of aggregated 60 nm entities with a dendritic structure were synthesized and exposed to zebrafish embryos assessing mortality and developmental defects. Ni NPs exposure was compared to soluble nickel salts. All three 30, 60, and 100 nm Ni NPs are equal to or less toxic than soluble nickel while dendritic clusters were more toxic. With each Ni NP exposure, thinning of the intestinal epithelium first occurs around the LD10 continuing into the LD50. LD50 exposure also results in skeletal muscle fiber separation. Exposure to soluble nickel does not cause intestinal defects while skeletal muscle separation occurs at concentrations well over LD50. These results suggest that configuration of nanoparticles may affect toxicity more than size and defects from Ni NPs exposure occur by different biological mechanisms than soluble nickel. PMID:19746736

Protective role of Parkin in skeletal muscle contractile and mitochondrial function.

PubMed

Gouspillou, Gilles; Godin, Richard; Piquereau, Jérome; Picard, Martin; Mofarrahi, Mahroo; Mathew, Jasmin; Purves-Smith, Fennigje M; Sgarioto, Nicolas; Hepple, Russell T; Burelle, Yan; Hussain, Sabah N A

2018-04-22

Parkin, an E3 ubiquitin ligase encoded by the Park2 gene, has been implicated in the regulation of mitophagy, a quality control process in which defective mitochondria are degraded. The exact physiological significance of Parkin in regulating mitochondrial function and contractility in skeletal muscle remains largely unexplored. Using Park2 -/- mice, we show that Parkin ablation causes a decrease in muscle specific force, a severe decrease in mitochondrial respiration, mitochondrial uncoupling and an increased susceptibility to opening of the permeability transition pore. These results demonstrate that Parkin plays a protective role in the maintenance of normal mitochondrial and contractile functions in skeletal muscles. Parkin is an E3 ubiquitin ligase encoded by the Park2 gene. Parkin has been implicated in the regulation of mitophagy, a quality control process in which defective mitochondria are sequestered in autophagosomes and delivered to lysosomes for degradation. Although Parkin has been mainly studied for its implication in neuronal degeneration in Parkinson disease, its role in other tissues remains largely unknown. In the present study, we investigated the skeletal muscles of Park2 knockout (Park2 -/- ) mice to test the hypothesis that Parkin plays a physiological role in mitochondrial quality control in normal skeletal muscle, a tissue highly reliant on mitochondrial content and function. We first show that the tibialis anterior (TA) of Park2 -/- mice display a slight but significant decrease in its specific force. Park2 -/ - muscles also show a trend for type IIB fibre hypertrophy without alteration in muscle fibre type proportion. Compared to Park2 +/+ muscles, the mitochondrial function of Park2 -/- skeletal muscles was significantly impaired, as indicated by the significant decrease in ADP-stimulated mitochondrial respiratory rates, uncoupling, reduced activities of respiratory chain complexes containing mitochondrial DNA (mtDNA)-encoded subunits

Intracortical circuits, sensorimotor integration and plasticity in human motor cortical projections to muscles of the lower face

PubMed Central

Pilurzi, G; Hasan, A; Saifee, T A; Tolu, E; Rothwell, J C; Deriu, F

2013-01-01

Previous studies of the cortical control of human facial muscles documented the distribution of corticobulbar projections and the presence of intracortical inhibitory and facilitatory mechanisms. Yet surprisingly, given the importance and precision in control of facial expression, there have been no studies of the afferent modulation of corticobulbar excitability or of the plasticity of synaptic connections in the facial primary motor cortex (face M1). In 25 healthy volunteers, we used standard single- and paired-pulse transcranial magnetic stimulation (TMS) methods to probe motor-evoked potentials (MEPs), short-intracortical inhibition, intracortical facilitation, short-afferent and long-afferent inhibition and paired associative stimulation in relaxed and active depressor anguli oris muscles. Single-pulse TMS evoked bilateral MEPs at rest and during activity that were larger in contralateral muscles, confirming that corticobulbar projection to lower facial muscles is bilateral and asymmetric, with contralateral predominance. Both short-intracortical inhibition and intracortical facilitation were present bilaterally in resting and active conditions. Electrical stimulation of the facial nerve paired with a TMS pulse 5–200 ms later showed no short-afferent inhibition, but long-afferent inhibition was present. Paired associative stimulation tested with an electrical stimulation–TMS interval of 20 ms significantly facilitated MEPs for up to 30 min. The long-term potentiation, evoked for the first time in face M1, demonstrates that excitability of the facial motor cortex is prone to plastic changes after paired associative stimulation. Evaluation of intracortical circuits in both relaxed and active lower facial muscles as well as of plasticity in the facial motor cortex may provide further physiological insight into pathologies affecting the facial motor system. PMID:23297305

Perforator Propeller Flap for Oncologic Reconstruction of Soft Tissue Defects in Trunk and Extremities.

PubMed

Yu, Shengji; Zang, Mengqing; Xu, Libin; Zhao, Zhenguo; Zhang, Xinxin; Zhu, Shan; Chen, Bo; Ding, Qiang; Liu, Yuanbo

2016-10-01

Defects after soft tissue sarcoma resection are usually managed by myocutaneous flaps or free flaps. However, harvesting muscle will cause functional morbidities, and some regions lack reliable recipient vessel. Our purpose is to use various perforator propeller flaps for oncologic reconstruction. Between 2008 and 2014, 33 perforator propeller flaps were performed in 24 patients to reconstruct the defects after tumor resection in trunk and extremities. Fifteen patients underwent tumor resection previously. Thirteen patients underwent adjuvant radiotherapy or chemotherapy. Flaps based on perforators adjacent to the lesions were raised and rotated in propeller fashion to repair the defects. Twenty-seven flaps were based on perforators of known source vessels, and 6 were harvested in freestyle fashion. The defects were repaired with 2 flaps in 4 patients and 3 flaps in 2 patients. The mean skin paddle dimension was 8.36 cm in width and 20.42 cm in length. The mean degree of flap rotation was 158.79°. Complications include partial necrosis of 6 flaps in 5 cases and venous congestion of 1 flap. In these 6 patients, 3 underwent adjuvant radiotherapy. The donor sites were primarily closed in 21 patients and skin grafted in 3 patients. No functional loss related to flap harvesting was recognized. The perforator propeller flaps can be used to manage the medium defects in extremities and large defects in torso after soft tissue sarcoma resection. They avoid the sacrifice of the underlying muscle and eliminate the concerns of the unavailability of recipient vessels. The perforator propeller flaps provide flexible options for versatile oncologic reconstruction in trunk and extremities. However, the impact of radiotherapy on the viability of the flaps for local reconstruction needs further investigation.

A qualitative analysis of Māori and Pacific smokers' views on informed choice and smoking.

PubMed

Gifford, Heather; Tautolo, El-Shadan; Erick, Stephanie; Hoek, Janet; Gray, Rebecca; Edwards, Richard

2016-05-17

Tobacco companies frame smoking as an informed choice, a strategy that holds individuals responsible for harms they incur. Few studies have tested this argument, and even fewer have examined how informed indigenous smokers or those from minority ethnicities are when they start smoking. We explored how young adult Māori and Pacific smokers interpreted 'informed choice' in relation to smoking. Using recruitment via advertising, existing networks and word of mouth, we recruited and undertook qualitative in-depth interviews with 20 Māori and Pacific young adults aged 18-26 years who smoked. Data were analysed using an informed-choice framework developed by Chapman and Liberman. We used a thematic analysis approach to identify themes that extended this framework. Few participants considered themselves well informed and none met more than the framework's initial two criteria. Most reflected on their unthinking uptake and subsequent addiction, and identified environmental factors that had facilitated uptake. Nonetheless, despite this context, most agreed that they had made an informed choice to smoke. The discrepancy between participants' reported knowledge and understanding of smoking's risks, and their assessment of smoking as an informed choice, reflects their view of smoking as a symbol of adulthood. Policies that make tobacco more difficult to use in social settings could help change social norms around smoking and the ease with which initiation and addiction currently occur. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Reconstruction of infected abdominal wall defects using latissimus dorsi free flap.

PubMed

Kim, Sang Wha; Han, Sang Chul; Hwang, Kyu Tae; Ahn, Byung Kyu; Kim, Jeong Tae; Kim, Youn Hwan

2013-12-01

Infected abdominal defects are a challenge to surgeons. In this study, we describe 10 cases in which the latissimus dorsi myocutaneous flap was used for successful reconstruction of abdominal wall defects severely infected with methicillin-resistant Staphylococcus aureus (MRSA). Retrospective review of 10 patients with abdominal wall defects that were reconstructed using the latissimus dorsi myocutaneous flap between 2002 and 2010. All patients had abdominal defects with hernias, combined with MRSA infections. The sizes of the flaps ranged from 120 to 364 cm(2) . The deep inferior epigastric artery was the recipient vessel in nine patients and the internal mammary vessels were used for one patient. There were no complications relating to the flaps, although there were other minor complications including wound dehiscence, haematoma and fluid correction. After reconstruction, there were no signs of infection during follow-up periods, and the patients were satisfied with the final results. Reconstruction using the latissimus dorsi myocutaneous flap, including muscle fascia structures, is a potential treatment option for severely infected large abdominal wall defects. © 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.

Muscle ERRγ mitigates Duchenne muscular dystrophy via metabolic and angiogenic reprogramming.

PubMed

Matsakas, Antonios; Yadav, Vikas; Lorca, Sabina; Narkar, Vihang

2013-10-01

Treatment of Duchenne muscular dystrophy (DMD) by replacing mutant dystrophin or restoring dystrophin-associated glycoprotein complex (DAG) has been clinically challenging. Instead, identifying and targeting muscle pathways deregulated in DMD will provide new therapeutic avenues. We report that the expression of nuclear receptor estrogen-related receptor-γ (ERRγ), and its metabolic and angiogenic targets are down-regulated (50-85%) in skeletal muscles of mdx mice (DMD model) vs. wild-type mice. Corelatively, oxidative myofibers, muscle vasculature, and exercise tolerance (33%) are decreased in mdx vs. wild-type mice. Overexpressing ERRγ selectively in the dystrophic muscles of the mdx mice restored metabolic and angiogenic gene expression compared with control mdx mice. Further, ERRγ enhanced muscle oxidative myofibers, vasculature, and blood flow (by 33-66%) and improved exercise tolerance (by 75%) in the dystrophic mice. Restoring muscle ERRγ pathway ameliorated muscle damage and also prevented DMD hallmarks of postexercise muscle damage, hypoxia, and fatigue in mdx mice. Notably, ERRγ did not restore sarcolemmal DAG complex, which is thus dispensable for antidystrophic effects of ERRγ. In summary, ERRγ-dependent metabolic and angiogenic gene program is defective in DMD, and we demonstrate that its restoration is a potential strategy for treating muscular dystrophy.

Electrical stimulation to the trigeminal proprioceptive fibres that innervate the mechanoreceptors in Müller's muscle induces involuntary reflex contraction of the frontalis muscles.

PubMed

Matsuo, Kiyoshi; Osada, Yoshiro; Ban, Ryokuya

2013-02-01

The levator and frontalis muscles lack interior muscle spindles, despite consisting of slow-twitch fibres that involuntarily sustain eyelid-opening and eyebrow-raising against gravity. To compensate for this anatomical defect, this study hypothetically proposes that initial voluntary contraction of the levator fast-twitch muscle fibres stretches the mechanoreceptors in Müller's muscle and evokes proprioception, which continuously induces reflex contraction of slow-twitch fibres of the levator and frontalis muscles. This study sought to determine whether unilateral transcutaneous electrical stimulation to the trigeminal proprioceptive fibres that innervate the mechanoreceptors in Müller's muscle could induce electromyographic responses in the frontalis muscles, with monitoring responses in the orbicularis oculi muscles. The study population included 27 normal subjects and 23 subjects with aponeurotic blepharoptosis, who displayed persistently raised eyebrows on primary gaze and light eyelid closure. The stimulation induced a short-latency response in the ipsilateral frontalis muscle of all subjects and long-latency responses in the bilateral frontalis muscles of normal subjects. However, it did not induce long-latency responses in the bilateral frontalis muscles of subjects with aponeurotic blepharoptosis. The orbicularis oculi muscles showed R1 and/or R2 responses. The stimulation might reach not only the proprioceptive fibres, but also other sensory fibres related to the blink or corneal reflex. The experimental system can provoke a monosynaptic short-latency response in the ipsilateral frontalis muscle, probably through the mesencephalic trigeminal proprioceptive neuron and the frontalis motor neuron, and polysynaptic long-latency responses in the bilateral frontalis muscles through an unknown pathway. The latter neural circuit appeared to be engaged by the circumstances of aponeurotic blepharoptosis.

Cost and Affordability of Diets Modelled on Current Eating Patterns and on Dietary Guidelines, for New Zealand Total Population, Māori and Pacific Households.

PubMed

Mackay, Sally; Buch, Tina; Vandevijvere, Stefanie; Goodwin, Rawinia; Korohina, Erina; Funaki-Tahifote, Mafi; Lee, Amanda; Swinburn, Boyd

2018-06-13

The affordability of diets modelled on the current (less healthy) diet compared to a healthy diet based on Dietary Guidelines was calculated for population groups in New Zealand. Diets using common foods were developed for a household of four for the total population, Māori and Pacific groups. Māori and Pacific nutrition expert panels ensured the diets were appropriate. Each current (less healthy) diet was based on eating patterns identified from national nutrition surveys. Food prices were collected from retail outlets. Only the current diets contained alcohol, takeaways and discretionary foods. The modelled healthy diet was cheaper than the current diet for the total population (3.5% difference) and Pacific households (4.5% difference) and similar in cost for Māori households (0.57% difference). When the diets were equivalent in energy, the healthy diet was more expensive than the current diet for all population groups (by 8.5% to 15.6%). For households on the minimum wage, the diets required 27% to 34% of household income, and if receiving income support, required 41⁻52% of household income. Expert panels were invaluable in guiding the process for specific populations. Both the modelled healthy and current diets are unaffordable for some households as a considerable portion of income was required to purchase either diet. Policies are required to improve food security by lowering the cost of healthy food or improving household income.

Lethality of sortase depletion in Actinomyces oris caused by excessive membrane accumulation of a surface glycoprotein.

PubMed

Wu, Chenggang; Huang, I-Hsiu; Chang, Chungyu; Reardon-Robinson, Melissa Elizabeth; Das, Asis; Ton-That, Hung

2014-12-01

Sortase, a cysteine-transpeptidase conserved in Gram-positive bacteria, anchors on the cell wall many surface proteins that facilitate bacterial pathogenesis and fitness. Genetic disruption of the housekeeping sortase in several Gram-positive pathogens reported thus far attenuates virulence, but not bacterial growth. Paradoxically, we discovered that depletion of the housekeeping sortase SrtA was lethal for Actinomyces oris; yet, all of its predicted cell wall-anchored protein substrates (AcaA-N) were individually dispensable for cell viability. Using Tn5-transposon mutagenesis to identify factors that upend lethality of srtA deletion, we uncovered a set of genetic suppressors harbouring transposon insertions within genes of a locus encoding AcaC and a LytR-CpsA-Psr (LCP)-like protein. AcaC was shown to be highly glycosylated and dependent on LCP for its glycosylation. Upon SrtA depletion, the glycosylated form of AcaC, hereby renamed GspA, was accumulated in the membrane. Overexpression of GspA in a mutant lacking gspA and srtA was lethal; conversely, cells overexpressing a GspA mutant missing a membrane-localization domain were viable. The results reveal a unique glycosylation pathway in A. oris that is coupled to cell wall anchoring catalysed by sortase SrtA. Significantly, this novel phenomenon of glyco-stress provides convenient cell-based assays for developing a new class of inhibitors against Gram-positive pathogens. © 2014 John Wiley & Sons Ltd.

Targeted deletion of RIC8A in mouse neural precursor cells interferes with the development of the brain, eyes, and muscles.

PubMed

Kask, Keiu; Tikker, Laura; Ruisu, Katrin; Lulla, Sirje; Oja, Eva-Maria; Meier, Riho; Raid, Raivo; Velling, Teet; Tõnissoo, Tambet; Pooga, Margus

2018-04-01

Autosomal recessive disorders such as Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, and the muscle-eye-brain disease are characterized by defects in the development of patient's brain, eyes, and skeletal muscles. These syndromes are accompanied by brain malformations like type II lissencephaly in the cerebral cortex with characteristic overmigrations of neurons through the breaches of the pial basement membrane. The signaling pathways activated by laminin receptors, dystroglycan and integrins, control the integrity of the basement membrane, and their malfunctioning may underlie the pathologies found in the rise of defects reminiscent of these syndromes. Similar defects in corticogenesis and neuromuscular disorders were found in mice when RIC8A was specifically removed from neural precursor cells. RIC8A regulates a subset of G-protein α subunits and in several model organisms, it has been reported to participate in the control of cell division, signaling, and migration. Here, we studied the role of RIC8A in the development of the brain, muscles, and eyes of the neural precursor-specific conditional Ric8a knockout mice. The absence of RIC8A severely affected the attachment and positioning of radial glial processes, Cajal-Retzius' cells, and the arachnoid trabeculae, and these mice displayed additional defects in the lens, skeletal muscles, and heart development. All the discovered defects might be linked to aberrancies in cell adhesion and migration, suggesting that RIC8A has a crucial role in the regulation of cell-extracellular matrix interactions and that its removal leads to the phenotype characteristic to type II lissencephaly-associated diseases. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 374-390, 2018. © 2018 Wiley Periodicals, Inc.

Channelopathies of skeletal muscle excitability

PubMed Central

Cannon, Stephen C.

2016-01-01

Familial disorders of skeletal muscle excitability were initially described early in the last century and are now known to be caused by mutations of voltage-gated ion channels. The clinical manifestations are often striking, with an inability to relax after voluntary contraction (myotonia) or transient attacks of severe weakness (periodic paralysis). An essential feature of these disorders is fluctuation of symptoms that are strongly impacted by environmental triggers such as exercise, temperature, or serum K+ levels. These phenomena have intrigued physiologists for decades, and in the past 25 years the molecular lesions underlying these disorders have been identified and mechanistic studies are providing insights for therapeutic strategies of disease modification. These familial disorders of muscle fiber excitability are “channelopathies” caused by mutations of a chloride channel (ClC-1), sodium channel (NaV1.4), calcium channel (CaV1.1) and several potassium channels (Kir2.1, Kir2.6, Kir3.4). This review provides a synthesis of the mechanistic connections between functional defects of mutant ion channels, their impact on muscle excitability, how these changes cause clinical phenotypes, and approaches toward therapeutics. PMID:25880512

Introduction à une théorie des systèmes composites : exemples simples de matériaux lamellaires

NASA Astrophysics Data System (ADS)

Akjouj, A.; Sylla, B.; Dobrzynski, L.

This review paper is mostly an introduction to the linear response theory for composite systems. The composite materials are defined here as being formed by different homogeneous parts connected together by interfaces. This type of material can be constructed with the help of homogeneous "bricks" cuted out from infinite materials. This cutting procedures are realized with the help of cleavage operators. The "bricks" are then put together by a coupling operator. This construction manner enables to obtain for any composite system a general equation relating the composite response function (called also Green's function) to the elements of the infinite material response functions and to the cleavage and coupling operators. A general and unified formulation valid as well in matrix algebra as in the algebra of differential equations results from this approach. Any general theory is abstract ; simple examples help very much to understand it. The principal aim of this review paper is the introduction of a general theory for composite systems through simple and analytical examples from the fields of phonons, magnons and electrons in the lamellar composite materials. In order to achieve this goal, the algebra of the examples is as explicit as possible. The references of what was already realized in theory of composite response are discussed also. A prospective and non exhaustive study of all the fields where such a theory can prove to be helpful is given also in this review paper. Cet article de revue est essentiellement une introduction à la théorie de la réponse linéaire dans les systèmes composites. Les matériaux composites sont définis ici comme étant formés de parties homogènes différentes reliées par des interfaces. Ce type de matériaux peut être construit à partir de "briques" homogènes découpées dans des matériaux infinis. Ces opérations de découpage sont effectuées par l'intermédiaire d'opérateurs de clivage. Les "briques" sont ensuite

Pelvic floor muscle lesions at endoanal MR imaging in female patients with faecal incontinence.

PubMed

Terra, Maaike P; Beets-Tan, Regina G H; Vervoorn, Inge; Deutekom, Marije; Wasser, Martin N J M; Witkamp, Theo D; Dobben, Annette C; Baeten, Cor G M I; Bossuyt, Patrick M M; Stoker, Jaap

2008-09-01

To evaluate the frequency and spectrum of lesions of different pelvic floor muscles at endoanal MRI in women with severe faecal incontinence and to study their relation with incontinence severity and manometric findings. In 105 women MRI examinations were evaluated for internal anal sphincter (IAS), external anal sphincter (EAS), puborectal muscle (PM) and levator ani (LA) lesions. The relative contribution of lesions to differences in incontinence severity and manometric findings was studied. IAS (n = 59) and EAS (n = 61) defects were more common than PM (n = 23) and LA (n = 26) defects. PM and LA defects presented mainly with IAS and/or EAS defects (isolated n = 2 and n = 3). EAS atrophy (n = 73) was more common than IAS (n = 19), PM (n = 16) and LA (n = 9) atrophy and presented mainly isolated. PM and LA atrophy presented primarily with EAS atrophy (isolated n = 3 and n = 1). Patients with IAS and EAS lesions had a lower resting and squeeze pressure, respectively; no other associations were found. PM and LA lesions are relatively common in patients with severe faecal incontinence, but the majority of lesions are found in women who also have IAS and/or EAS lesions. Only an association between anal sphincter lesions and manometry was observed.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia

PubMed Central

Pitceathly, Robert D. S.; Blake, Julian C.; Woodward, Catherine E.; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E.; Plant, Gordon T.; Houlden, Henry; Sweeney, Mary G.; Hanna, Michael G.; Reilly, Mary M.

2014-01-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P < 0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P = 0.002; odds ratio 8.43, 95% confidence

Case Report Reconstruction of Exposed Ilium With Reverse Turnover Latissimus Dorsi Muscle Flap

PubMed Central

Hayashida, Kenji; Endo, Yoshie; Kamebuchi, Katsuhiko

2011-01-01

Objective: It is difficult to cover a large skin and soft tissue defect with exposure of the ilium. We therefore performed a new reconstruction technique, using a reverse latissimus dorsi muscle flap fed by perforating branches of only the 10th intercostal artery. Methods: A 45-year-old man had a large traumatic defect located on the hip with exposure of the iliac crest. After confirming and preserving perforating branches of the 10th intercostal artery, the latissimus dorsi muscle flap was turned over just proximal to the perforating branch, and a split-thickness skin graft was performed over the flap. Results: The skin graft took place well and there were no circulation problems. Conclusions: This flap covered a larger area on the hip than the musculocutaneous flap. Furthermore, this is easier to perform and is less invasive than a vascularized free flap. Skin and soft tissue defects that expose bones of the lumbar or hip region can be reconstructed with a local flap; however, the deficit is small for this coverage and usually there is little skin and soft tissue to cover the wound defect in the surrounding area. Thus, it is often difficult to deal with large defects. We performed a reconstruction, using a reverse latissimus dorsi flap fed by perforating branches of the 10th intercostal artery for a large skin and soft tissue defect of the hip with exposure of the iliac crest, resulting in a good outcome. This technique is thought to be useful for reconstruction when the ilium is exposed, and we report the case and surgical procedure. PMID:21559059

A reliable approach to the closure of large acquired midline defects of the back

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casas, L.A.; Lewis, V.L. Jr.

1989-10-01

A systematic regionalized approach for the reconstruction of acquired thoracic and lumbar midline defects of the back is described. Twenty-three patients with wounds resulting from pressure necrosis, radiation injury, and postoperative wound infection and dehiscence were successfully reconstructed. The latissimus dorsi, trapezius, gluteus maximus, and paraspinous muscles are utilized individually or in combination as advancement, rotation, island, unipedicle, turnover, or bipedicle flaps. All flaps are designed so that their vascular pedicles are out of the field of injury. After thorough debridement, large, deep wounds are closed with two layers of muscle, while smaller, more superficial wounds are reconstructed with onemore » layer. The trapezius muscle is utilized in the high thoracic area for the deep wound layer, while the paraspinous muscle is used for this layer in the thoracic and lumbar regions. Superficial layer and small wounds in the high thoracic area are reconstructed with either latissimus dorsi or trapezius muscle. Corresponding wounds in the thoracic and lumbar areas are closed with latissimus dorsi muscle alone or in combination with gluteus maximus muscle. The rationale for systematic regionalized reconstruction of acquired midline back wounds is described.« less

Repair of traumatic skeletal muscle injury with bone-marrow-derived mesenchymal stem cells seeded on extracellular matrix.

PubMed

Merritt, Edward K; Cannon, Megan V; Hammers, David W; Le, Long N; Gokhale, Rohit; Sarathy, Apurva; Song, Tae J; Tierney, Matthew T; Suggs, Laura J; Walters, Thomas J; Farrar, Roger P

2010-09-01

Skeletal muscle injury resulting in tissue loss poses unique challenges for surgical repair. Despite the regenerative potential of skeletal muscle, if a significant amount of tissue is lost, skeletal myofibers will not grow to fill the injured area completely. Prior work in our lab has shown the potential to fill the void with an extracellular matrix (ECM) scaffold, resulting in restoration of morphology, but not functional recovery. To improve the functional outcome of the injured muscle, a muscle-derived ECM was implanted into a 1 x 1 cm(2), full-thickness defect in the lateral gastrocnemius (LGAS) of Lewis rats. Seven days later, bone-marrow-derived mesenchymal stem cells (MSCs) were injected directly into the implanted ECM. Partial functional recovery occurred over the course of 42 days when the LGAS was repaired with an MSC-seeded ECM producing 85.4 +/- 3.6% of the contralateral LGAS. This was significantly higher than earlier recovery time points (p < 0.05). The specific tension returned to 94 +/- 9% of the contralateral limb. The implanted MSC-seeded ECM had more blood vessels and regenerating skeletal myofibers than the ECM without cells (p < 0.05). The data suggest that the repair of a skeletal muscle defect injury by the implantation of a muscle-derived ECM seeded with MSCs can improve functional recovery after 42 days.

Crisis engagement in mental health: a New Zealand Māori contribution.

PubMed

Drury, Nick; Munro, Te Ata

2008-10-01

The active engagement of clients in mental health services offers far greater chances of successful outcomes. When clients do not actively engage in treatment, their risk of becoming part of the population of 'high users' is greater. The 'high users' consume a disproportionate share of health resources, which may prevent other potential clients from accessing services. Engagement can be particularly challenging in crisis situations, which is how many clients attracting psychotic diagnoses first enter the service. New Zealand Māori bring a transcendent quality to the idea of 'respect for Other', which would make it sacrilegious to overpower Other in most situations. This paper reviews a growing body of literature indicating how we might integrate an enhanced respect or reverence of Other into clinical practice. This includes the idea of engaging more frequently with the social network when building rapport with an individual is particularly challenging. There is some evidence that services adopting this kind of approach are more economical.

Topological defects in confined populations of spindle-shaped cells

NASA Astrophysics Data System (ADS)

Duclos, Guillaume; Erlenkämper, Christoph; Joanny, Jean-François; Silberzan, Pascal

2017-01-01

Most spindle-shaped cells (including smooth muscles and sarcomas) organize in vivo into well-aligned `nematic’ domains, creating intrinsic topological defects that may be used to probe the behaviour of these active nematic systems. Active non-cellular nematics have been shown to be dominated by activity, yielding complex chaotic flows. However, the regime in which live spindle-shaped cells operate, and the importance of cell-substrate friction in particular, remains largely unexplored. Using in vitro experiments, we show that these active cellular nematics operate in a regime in which activity is effectively damped by friction, and that the interaction between defects is controlled by the system’s elastic nematic energy. Due to the activity of the cells, these defects behave as self-propelled particles and pairwise annihilate until all displacements freeze as cell crowding increases. When confined in mesoscopic circular domains, the system evolves towards two identical +1/2 disclinations facing each other. The most likely reduced positions of these defects are independent of the size of the disk, the cells’ activity or even the cell type, but are well described by equilibrium liquid crystal theory. These cell-based systems thus operate in a regime more stable than other active nematics, which may be necessary for their biological function.

Myopathic changes in murine skeletal muscle lacking synemin

PubMed Central

García-Pelagio, Karla P.; Muriel, Joaquin; O'Neill, Andrea; Desmond, Patrick F.; Lovering, Richard M.; Lund, Linda; Bond, Meredith

2015-01-01

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. Tibialis anterior (TA) muscles show a significant decrease in mean fiber diameter, a decrease in twitch and tetanic force, and an increase in susceptibility to injury caused by lengthening contractions. Organization of proteins associated with the contractile apparatus and costameres is not significantly altered in the synm-null. Elastimetry of the sarcolemma and associated contractile apparatus in extensor digitorum longus myofibers reveals a reduction in tension consistent with an increase in sarcolemmal deformability. Although fatigue after repeated isometric contractions is more marked in TA muscles of synm-null mice, the ability of the mice to run uphill on a treadmill is similar to controls. Our results suggest that synemin contributes to linkage between costameres and the contractile apparatus and that the absence of synemin results in decreased fiber size and increased sarcolemmal deformability and susceptibility to injury. Thus synemin plays a moderate but distinct role in fast twitch skeletal muscle. PMID:25567810

Compromised genomic integrity impedes muscle growth after Atrx inactivation

PubMed Central

Huh, Michael S.; Price O’Dea, Tina; Ouazia, Dahmane; McKay, Bruce C.; Parise, Gianni; Parks, Robin J.; Rudnicki, Michael A.; Picketts, David J.

2012-01-01

ATR-X syndrome is a severe intellectual disability disorder caused by mutations in the ATRX gene. Many ancillary clinical features are attributed to CNS deficiencies, yet most patients have muscle hypotonia, delayed ambulation, or kyphosis, pointing to an underlying skeletal muscle defect. Here, we identified a cell-intrinsic requirement for Atrx in postnatal muscle growth and regeneration in mice. Mice with skeletal muscle–specific Atrx conditional knockout (Atrx cKO mice) were viable, but by 3 weeks of age presented hallmarks of underdeveloped musculature, including kyphosis, 20% reduction in body mass, and 34% reduction in muscle fiber caliber. Atrx cKO mice also demonstrated a marked regeneration deficit that was not due to fewer resident satellite cells or their inability to terminally differentiate. However, activation of Atrx-null satellite cells from isolated muscle fibers resulted in a 9-fold reduction in myoblast expansion, caused by delayed progression through mid to late S phase. While in S phase, Atrx colocalized specifically to late-replicating chromatin, and its loss resulted in rampant signs of genomic instability. These observations support a model in which Atrx maintains chromatin integrity during the rapid developmental growth of a tissue. PMID:23114596

The Architecture of the GW Ori Young Triple-star System and Its Disk: Dynamical Masses, Mutual Inclinations, and Recurrent Eclipses

NASA Astrophysics Data System (ADS)

Czekala, Ian; Andrews, Sean M.; Torres, Guillermo; Rodriguez, Joseph E.; Jensen, Eric L. N.; Stassun, Keivan G.; Latham, David W.; Wilner, David J.; Gully-Santiago, Michael A.; Grankin, Konstantin N.; Lund, Michael B.; Kuhn, Rudolf B.; Stevens, Daniel J.; Siverd, Robert J.; James, David; Gaudi, B. Scott; Shappee, Benjamin J.; Holoien, Thomas W.-S.

2017-12-01

We present spatially and spectrally resolved Atacama Large Millimeter/submillimeter Array (ALMA) observations of gas and dust orbiting the pre-main-sequence hierarchical triple-star system GW Ori. A forward modeling of the 13CO and C18O J = 2–1 transitions permits a measurement of the total stellar mass in this system, 5.29+/- 0.09 {M}ȯ , and the circumtriple disk inclination, 137\\buildrel{\\circ}\\over{.} 6+/- 2\\buildrel{\\circ}\\over{.} 0. Optical spectra spanning a 35 yr period were used to derive new radial velocities and, coupled with a spectroscopic disentangling technique, revealed that the A and B components of GW Ori form a double-lined spectroscopic binary with a period of 241.50 ± 0.05 days; a tertiary companion orbits that inner pair with a period of 4218 ± 50 days. Combining the results from the ALMA data and the optical spectra with three epochs of astrometry in the literature, we constrain the individual stellar masses in the system ({M}{{A}}≈ 2.7 {M}ȯ , {M}{{B}}≈ 1.7 {M}ȯ , {M}{{C}}≈ 0.9 {M}ȯ ) and find strong evidence that at least one of the stellar orbital planes (and likely both) is misaligned with the disk plane by as much as 45°. A V-band light curve spanning 30 yr reveals several new ∼30-day eclipse events 0.1–0.7 mag in depth and a 0.2 mag sinusoidal oscillation that is clearly phased with the AB–C orbital period. Taken together, these features suggest that the A–B pair may be partially obscured by material in the inner disk as the pair approaches apoastron in the hierarchical orbit. Lastly, we conclude that stellar evolutionary models are consistent with our measurements of the masses and basic photospheric properties if the GW Ori system is ∼1 Myr old.

A novel technique for ventral orbital stabilization: the masseter muscle flap.

PubMed

Sivagurunathan, Amilan; Boy, Sonja C; Steenkamp, Gerhard

2014-01-01

Loss of the caudal maxilla and ventral orbit after tumor resections can have negative functional and esthetic influences on the eye involved. This article reports on a case of a caudal maxillary acanthomatous ameloblastoma involving the ventral orbit that was resected and stabilized with a masseter muscle flap. The masseter muscle flap was generated from the superficial belly of the masseter muscle in order to close a defect in the orbital rim, created by a caudal maxillectomy. None of the published complications such as enophthalmos, excessive lacrimation, globe deviation, or strabismus were noted, 8 months following the procedure. The only clinical sign present at the time of re-evaluation was mild lacrimation. The authors propose the use of a masseter muscle flap as a viable technique in stabilizing the ventral orbit after caudal maxillectomy and ventral orbitectomy, preventing the complications associated with this surgery. © 2013 American College of Veterinary Ophthalmologists.

Differentiated muscles are mandatory for gas-filling of the Drosophila airway system.

PubMed

Wang, Yiwen; Cruz, Tina; Irion, Uwe; Moussian, Bernard

2015-11-30

At the end of development, organs acquire functionality, thereby ensuring autonomy of an organism when it separates from its mother or a protective egg. In insects, respiratory competence starts when the tracheal system fills with gas just before hatching of the juvenile animal. Cellular and molecular mechanisms of this process are not fully understood. Analyses of the phenotype of Drosophila embryos with malformed muscles revealed that they fail to gas-fill their tracheal system. Indeed, we show that major regulators of muscle formation like Lame duck and Blown fuse are important, while factors involved in the development of subsets of muscles including cardiac and visceral muscles are dispensable for this process, suggesting that somatic muscles (or parts of them) are essential to enable tracheal terminal differentiation. Based on our phenotypic data, we assume that somatic muscle defect severity correlates with the penetrance of the gas-filling phenotype. This argues that a limiting molecular or mechanical muscle-borne signal tunes tracheal differentiation. We think that in analogy to the function of smooth muscles in vertebrate lungs, a balance of physical forces between muscles and the elasticity of tracheal walls may be decisive for tracheal terminal differentiation in Drosophila. © 2015. Published by The Company of Biologists Ltd.

Altered Splicing of the BIN1 Muscle-Specific Exon in Humans and Dogs with Highly Progressive Centronuclear Myopathy

PubMed Central

Böhm, Johann; Vasli, Nasim; Maurer, Marie; Cowling, Belinda; Shelton, G. Diane; Kress, Wolfram; Toussaint, Anne; Prokic, Ivana; Schara, Ulrike; Anderson, Thomas James; Weis, Joachim; Tiret, Laurent; Laporte, Jocelyn

2013-01-01

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies. PMID:23754947

Deletion of Skeletal Muscle SOCS3 Prevents Insulin Resistance in Obesity

PubMed Central

Jorgensen, Sebastian Beck; O’Neill, Hayley M.; Sylow, Lykke; Honeyman, Jane; Hewitt, Kimberly A.; Palanivel, Rengasamy; Fullerton, Morgan D.; Öberg, Lisa; Balendran, Anudharan; Galic, Sandra; van der Poel, Chris; Trounce, Ian A.; Lynch, Gordon S.; Schertzer, Jonathan D.; Steinberg, Gregory R.

2013-01-01

Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin signal transduction in adipose tissue and the liver. Skeletal muscle is an important tissue for controlling energy expenditure and whole-body insulin sensitivity; however, the physiological importance of SOCS3 in this tissue has not been examined. Therefore, we generated mice that had SOCS3 specifically deleted in skeletal muscle (SOCS MKO). The SOCS3 MKO mice had normal muscle development, body mass, adiposity, appetite, and energy expenditure compared with wild-type (WT) littermates. Despite similar degrees of obesity when fed a high-fat diet, SOCS3 MKO mice were protected against the development of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance. PMID:22961088

Distinct roles for Ste20-like kinase SLK in muscle function and regeneration

PubMed Central

2013-01-01

Background Cell growth and terminal differentiation are controlled by complex signaling systems that regulate the tissue-specific expression of genes controlling cell fate and morphogenesis. We have previously reported that the Ste20-like kinase SLK is expressed in muscle tissue and is required for cell motility. However, the specific function of SLK in muscle tissue is still poorly understood. Methods To gain further insights into the role of SLK in differentiated muscles, we expressed a kinase-inactive SLK from the human skeletal muscle actin promoter. Transgenic muscles were surveyed for potential defects. Standard histological procedures and cardiotoxin-induced regeneration assays we used to investigate the role of SLK in myogenesis and muscle repair. Results High levels of kinase-inactive SLK in muscle tissue produced an overall decrease in SLK activity in muscle tissue, resulting in altered muscle organization, reduced litter sizes, and reduced breeding capacity. The transgenic mice did not show any differences in fiber-type distribution but displayed enhanced regeneration capacity in vivo and more robust differentiation in vitro. Conclusions Our results show that SLK activity is required for optimal muscle development in the embryo and muscle physiology in the adult. However, reduced kinase activity during muscle repair enhances regeneration and differentiation. Together, these results suggest complex and distinct roles for SLK in muscle development and function. PMID:23815977

[Modified pectoralis major myocutaneous flap in reconstruction of head and neck defects].

PubMed

Chen, Jie; Huang, Wenxiao; Li, Zan; Zhou, Xiao; Yu, Jianjun; Bao, Ronghua; Zhang, Hailin; Ling, Hang

2015-05-01

To report the experience of use of modified pectoralis major myocutaneous (PMMC) flaps in reconstruction of head and neck postoperative defects. A total of 107 patients who underwent head and neck defect reconstruction using modified PMMC flaps after tumor rescetion between Jan 2008 and Dec 2013 were analyzed retrospectively. The success rate of reconstruction with modified PMMC flaps was 94.4% (101/107). Five patients had partial flap necrosis and their wounds healed with dressing change. One patient (0.9%) had total flap necrosis, followed by the second reconstruction using contralateral PMMC flap. The modified falcate PMMC flap can obtain optimum quantity of the skin in the chest and decreasing the closing tension of the donnor site in favor of wound healing. The pedicle without muscle will not only maintain the partial function of the pectoralis major, but also help to avoid pressing the vascular pedicle within the subclavian tunnel. The muscular element the pedicled muscles of the PMMC flap can increase the ability of the flap to resist infection, which can use for covering an exposed carotid artery and improving the neck fibrosis of irradiated patients.

Muscles provide protection during microbial infection by activating innate immune response pathways in Drosophila and zebrafish.

PubMed

Chatterjee, Arunita; Roy, Debasish; Patnaik, Esha; Nongthomba, Upendra

2016-06-01

Muscle contraction brings about movement and locomotion in animals. However, muscles have also been implicated in several atypical physiological processes including immune response. The role of muscles in immunity and the mechanism involved has not yet been deciphered. In this paper, using Drosophila indirect flight muscles (IFMs) as a model, we show that muscles are immune-responsive tissues. Flies with defective IFMs are incapable of mounting a potent humoral immune response. Upon immune challenge, the IFMs produce anti-microbial peptides (AMPs) through the activation of canonical signaling pathways, and these IFM-synthesized AMPs are essential for survival upon infection. The trunk muscles of zebrafish, a vertebrate model system, also possess the capacity to mount an immune response against bacterial infections, thus establishing that immune responsiveness of muscles is evolutionarily conserved. Our results suggest that physiologically fit muscles might boost the innate immune response of an individual. © 2016. Published by The Company of Biologists Ltd.

Increased aging in primary muscle cultures of sporadic inclusion-body myositis.

PubMed

Morosetti, Roberta; Broccolini, Aldobrando; Sancricca, Cristina; Gliubizzi, Carla; Gidaro, Teresa; Tonali, Pietro A; Ricci, Enzo; Mirabella, Massimiliano

2010-07-01

Ageing is thought to participate to the pathogenesis of sporadic inclusion-body myositis (s-IBM). Although the regenerative potential of s-IBM muscle is reduced in vivo, age-related abnormalities of satellite cells possibly accounting for the decline of muscle repair have not been demonstrated. Here we show that proliferation rate and clonogenicity of s-IBM myoblasts are significantly lower and doubling time is longer than normal age-matched controls, indicating that proliferative capacity of s-IBM muscles becomes exhausted earlier. Telomere shortening is detected in s-IBM cells suggesting premature senescence. Differently from controls, s-IBM myoblasts show increased active beta-catenin mainly localized within myonuclei, indicating active Wnt stimulation. After many rounds of muscle growth, only s-IBM myoblasts accumulate congophilic inclusions and immunoreactive Abeta(1-40) deposits. Therefore, s-IBM myoblasts seem to have a constitutively impaired regenerative capacity and the intrinsic property, upon sufficient aging in vitro, to accumulate Abeta. Our results might be valuable in understanding molecular mechanisms associated with muscle aging underlying the defective regeneration of s-IBM muscle and provide new clues for future therapeutic strategies. Copyright 2008 Elsevier Inc. All rights reserved.

Optimizing reconstruction of oncologic sternectomy defects based on surgical outcomes.

PubMed

Butterworth, James A; Garvey, Patrick B; Baumann, Donald P; Zhang, Hong; Rice, David C; Butler, Charles E

2013-08-01

The optimal strategy for oncologic sternectomy reconstruction has not been well characterized. We hypothesized that the major factors driving the reconstructive strategy for oncologic sternectomy include the need for skin replacement, extent of the bony sternectomy defect, and status of the internal mammary vessels. We reviewed consecutive oncologic sternectomy reconstructions performed at The University of Texas MD Anderson Cancer Center during a 10-year period. Regression models analyzed associations between patient, defect, and treatment factors and outcomes to identify patient and treatment selection criteria. We developed a generalized management algorithm based on these data. Forty-nine consecutive patients underwent oncologic sternectomy reconstruction (mean follow-up 18 ± 23 months). More sternectomies were partial (74%) rather than total/subtotal (26%). Most defects (n = 40 [82%]) required skeletal reconstruction. Pectoralis muscle flaps were most commonly used for sternectomies with intact overlying skin (64%) and infrequently used when a presternal skin defect was present (36%; p = 0.06). Free flaps were more often used for total/subtotal vs partial sternectomy defects (75% vs 25%, respectively; p = 0.02). Complication rates for total/subtotal sternectomy and partial sternectomy were equivalent (46% vs 44%, respectively; p = 0.92). Despite more extensive sternal resections, total/subtotal sternectomies resulted in equivalent postoperative complications when combined with the appropriate soft-tissue reconstruction. Good surgical and oncologic outcomes can be achieved with defect-characteristic-matched reconstructive strategies for these complex oncologic sternectomy resections. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Investigation of defect modes in a defective photonic crystal with a semiconductor metamaterial defect

NASA Astrophysics Data System (ADS)

Wu, Meng-Ru; Wu, Chien-Jang; Chang, Shoou-Jinn

2014-11-01

In this work, we theoretically investigate the properties of defect modes in a defective photonic crystal containing a semiconductor metamaterial defect. We consider the structure, (LH)N/DP/(LH)N, where N and P are respectively the stack numbers, L is SiO2, H is InP, and defect layer D is a semiconductor metamaterial composed of Al-doped ZnO (AZO) and ZnO. It is found that, within the photonic band gap, the number of defect modes (transmission peaks) will decrease as the defect thickness increases, in sharp contrast to the case of using usual dielectric defect. The peak height and position can be changed by the variation in the thickness of defect layer. In the angle-dependent defect mode, its position is shown to be blue-shifted as the angle of incidence increases for both TE and TM waves. The analysis of defect mode provides useful information for the design of tunable transmission filter in semiconductor optoelectronics.

Lipin-1 regulates Bnip3-mediated mitophagy in glycolytic muscle.

PubMed

Alshudukhi, Abdullah A; Zhu, Jing; Huang, Dengtong; Jama, Abdulrahman; Smith, Jeffrey D; Wang, Qing Jun; Esser, Karyn A; Ren, Hongmei

2018-06-25

Autophagy of mitochondria (mitophagy) is essential for maintaining muscle mass and healthy skeletal muscle. Patients with heritable phosphatidic acid phosphatase lipin-1-null mutations present with severe rhabdomyolysis and muscle atrophy in glycolytic muscle fibers, which are accompanied with mitochondrial aggregates and reduced mitochondrial cytochrome c oxidase activity. However, the underlying mechanisms leading to muscle atrophy as a result of lipin-1 deficiency are still not clear. In this study, we found that lipin-1 deficiency in mice is associated with a marked accumulation of abnormal mitochondria and autophagic vacuoles in glycolytic muscle fibers. Our studies using lipin-1-deficient myoblasts suggest that lipin-1 participates in B-cell leukemia (BCL)-2 adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3)-regulated mitophagy by interacting with microtubule-associated protein 1A/1B-light chain (LC)3, which is an important step in the recruitment of mitochondria to nascent autophagosomes. The requirement of lipin-1 for Bnip3-mediated mitophagy was further verified in vivo in lipin-1-deficient green fluorescent protein-LC3 transgenic mice (lipin-1 -/- -GFP-LC3). Finally, we showed that lipin-1 deficiency in mice resulted in defective mitochondrial adaptation to starvation-induced metabolic stress and impaired contractile muscle force in glycolytic muscle fibers. In summary, our study suggests that deregulated mitophagy arising from lipin-1 deficiency is associated with impaired muscle function and may contribute to muscle rhabdomyolysis in humans.-Alshudukhi, A. A., Zhu, J., Huang, D., Jama, A., Smith, J. D., Wang, Q. J., Esser, K. A., Ren, H. Lipin-1 regulates Bnip3-mediated mitophagy in glycolytic muscle.

Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy.

PubMed

Nicole, Sophie; Chaouch, Amina; Torbergsen, Torberg; Bauché, Stéphanie; de Bruyckere, Elodie; Fontenille, Marie-Joséphine; Horn, Morten A; van Ghelue, Marijke; Løseth, Sissel; Issop, Yasmin; Cox, Daniel; Müller, Juliane S; Evangelista, Teresinha; Stålberg, Erik; Ioos, Christine; Barois, Annie; Brochier, Guy; Sternberg, Damien; Fournier, Emmanuel; Hantaï, Daniel; Abicht, Angela; Dusl, Marina; Laval, Steven H; Griffin, Helen; Eymard, Bruno; Lochmüller, Hanns

2014-09-01

Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of rare diseases resulting from impaired neuromuscular transmission. Their clinical hallmark is fatigable muscle weakness associated with a decremental muscle response to repetitive nerve stimulation and frequently related to postsynaptic defects. Distal myopathies form another clinically and genetically heterogeneous group of primary muscle disorders where weakness and atrophy are restricted to distal muscles, at least initially. In both congenital myasthenic syndromes and distal myopathies, a significant number of patients remain genetically undiagnosed. Here, we report five patients from three unrelated families with a strikingly homogenous clinical entity combining congenital myasthenia with distal muscle weakness and atrophy reminiscent of a distal myopathy. MRI and neurophysiological studies were compatible with mild myopathy restricted to distal limb muscles, but decrement (up to 72%) in response to 3 Hz repetitive nerve stimulation pointed towards a neuromuscular transmission defect. Post-exercise increment (up to 285%) was observed in the distal limb muscles in all cases suggesting presynaptic congenital myasthenic syndrome. Immunofluorescence and ultrastructural analyses of muscle end-plate regions showed synaptic remodelling with denervation-reinnervation events. We performed whole-exome sequencing in two kinships and Sanger sequencing in one isolated case and identified five new recessive mutations in the gene encoding agrin. This synaptic proteoglycan with critical function at the neuromuscular junction was previously found mutated in more typical forms of congenital myasthenic syndrome. In our patients, we found two missense mutations residing in the N-terminal agrin domain, which reduced acetylcholine receptors clustering activity of agrin in vitro. Our findings expand the spectrum of congenital myasthenic syndromes due to agrin mutations and show an unexpected

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia.

PubMed

Horga, Alejandro; Pitceathly, Robert D S; Blake, Julian C; Woodward, Catherine E; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E; Plant, Gordon T; Houlden, Henry; Sweeney, Mary G; Hanna, Michael G; Reilly, Mary M

2014-12-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P<0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P=0.002; odds ratio 8.43, 95% confidence interval 2

Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its loss accelerates skeletal muscle aging process by altering calcium homeostasis.

PubMed

Romero-Suarez, Sandra; Shen, Jinhua; Brotto, Leticia; Hall, Todd; Mo, Chenglin; Valdivia, Héctor H; Andresen, Jon; Wacker, Michael; Nosek, Thomas M; Qu, Cheng-Kui; Brotto, Marco

2010-08-01

We have recently reported that a novel muscle-specific inositide phosphatase (MIP/MTMR14) plays a critical role in [Ca2+]i homeostasis through dephosphorylation of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5) bisphosphate (PI(3,5)P2). Loss of function mutations in MIP have been identified in human centronuclear myopathy. We developed a MIP knockout (MIPKO) animal model and found that MIPKO mice were more susceptible to exercise-induced muscle damage, a trademark of muscle functional changes in older subjects. We used wild-type (Wt) mice and MIPKO mice to elucidate the roles of MIP in muscle function during aging. We found MIP mRNA expression, MIP protein levels, and MIP phosphatase activity significantly decreased in old Wt mice. The mature MIPKO mice displayed phenotypes that closely resembled those seen in old Wt mice: i) decreased walking speed, ii) decreased treadmill activity, iii) decreased contractile force, and iv) decreased power generation, classical features of sarcopenia in rodents and humans. Defective Ca2+ homeostasis is also present in mature MIPKO and old Wt mice, suggesting a putative role of MIP in the decline of muscle function during aging. Our studies offer a new avenue for the investigation of MIP roles in skeletal muscle function and as a potential therapeutic target to treat aging sarcopenia.

Ca2+-ATPase deficiency in a patient with an exertional muscle pain syndrome.

PubMed Central

Taylor, D J; Brosnan, M J; Arnold, D L; Bore, P J; Styles, P; Walton, J; Radda, G K

1988-01-01

31P Magnetic resonance spectroscopy studies were carried out in vivo on skeletal muscle of a patient with verapamil-responsive, chronic, progressive post-exertional muscle pain. A sister suffered from a similar complaint. The results showed that the muscle: (1) decreased its high energy phosphate content more rapidly than normal during exercise, indicating either increased utilisation or decreased production of ATP; (2) acidified more rapidly than normal during exercise suggesting an increased glycolytic rate; (3) continued in some studies to acidify markedly during the first minute after exercise, indicating that glycolysis remained active into the recovery period; (4) had phosphocreatine and ADP recovery rates consistent with normal rates of oxidative phosphorylation. On the basis of these results, it was proposed that the patient suffers from a defect in Ca2+ handling in the muscle. Subsequently, direct measurement of Ca2+-ATPase activity in the sarcoplasmic reticulum fraction from a muscle biopsy sample showed that the activity of this enzyme was reduced by about 90%. PMID:2976810

Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157.

PubMed

Staresinic, Mario; Petrovic, Igor; Novinscak, Tomislav; Jukic, Ivana; Pevec, Damira; Suknaic, Slaven; Kokic, Neven; Batelja, Lovorka; Brcic, Luka; Boban-Blagaic, Alenka; Zoric, Zdenka; Ivanovic, Domagoj; Ajduk, Marko; Sebecic, Bozidar; Patrlj, Leonardo; Sosa, Tomislav; Buljat, Gojko; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

2006-05-01

We report complete transection of major muscle and the systemic peptide treatment that induces healing of quadriceps muscle promptly and then maintains the healing with functional restoration. Initially, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, PL-10, PLD-116, PL 14736 Pliva, Croatia; in trials for inflammatory bowel disease; wound treatment; no toxicity reported; effective alone without carrier) also superiorly accelerates the healing of transected Achilles tendon. Regularly, quadriceps muscle completely transected transversely 1.0 cm proximal to patella presents a definitive defect that cannot be compensated in rat. BPC 157 (10 microg, 10 ng, 10 pg/kg) is given intraperitoneally, once daily; the first application 30 min posttransection, the final 24 h before sacrifice. It consistently improves muscle healing throughout the whole 72-day period. Improved are: (i) biomechanic (load of failure increased); (ii) function (walking recovery and extensor postural thrust/motor function index returned toward normal healthy values); (iii) microscopy/immunochemistry [i.e., mostly muscle fibers connect muscle segments; absent gap; significant desmin positivity for ongoing regeneration of muscle; larger myofibril diameters on both sides, distal and proximal (normal healthy rat-values reached)]; (iv) macroscopic presentation (stumps connected; subsequently, atrophy markedly attenuated; finally, presentation close to normal noninjured muscle, no postsurgery leg contracture). Thus, posttransection healing-consistently improved-may suggest this peptide therapeutic application in muscle disorders. Copyright 2006 Orthopaedic Research Society.

Mesodermal iPSC–derived progenitor cells functionally regenerate cardiac and skeletal muscle

PubMed Central

Quattrocelli, Mattia; Swinnen, Melissa; Giacomazzi, Giorgia; Camps, Jordi; Barthélemy, Ines; Ceccarelli, Gabriele; Caluwé, Ellen; Grosemans, Hanne; Thorrez, Lieven; Pelizzo, Gloria; Muijtjens, Manja; Verfaillie, Catherine M.; Blot, Stephane; Janssens, Stefan; Sampaolesi, Maurilio

2015-01-01

Conditions such as muscular dystrophies (MDs) that affect both cardiac and skeletal muscles would benefit from therapeutic strategies that enable regeneration of both of these striated muscle types. Protocols have been developed to promote induced pluripotent stem cells (iPSCs) to differentiate toward cardiac or skeletal muscle; however, there are currently no strategies to simultaneously target both muscle types. Tissues exhibit specific epigenetic alterations; therefore, source-related lineage biases have the potential to improve iPSC-driven multilineage differentiation. Here, we determined that differential myogenic propensity influences the commitment of isogenic iPSCs and a specifically isolated pool of mesodermal iPSC-derived progenitors (MiPs) toward the striated muscle lineages. Differential myogenic propensity did not influence pluripotency, but did selectively enhance chimerism of MiP-derived tissue in both fetal and adult skeletal muscle. When injected into dystrophic mice, MiPs engrafted and repaired both skeletal and cardiac muscle, reducing functional defects. Similarly, engraftment into dystrophic mice of canine MiPs from dystrophic dogs that had undergone TALEN-mediated correction of the MD-associated mutation also resulted in functional striatal muscle regeneration. Moreover, human MiPs exhibited the same capacity for the dual differentiation observed in murine and canine MiPs. The findings of this study suggest that MiPs should be further explored for combined therapy of cardiac and skeletal muscles. PMID:26571398

Desmin Cytoskeleton Linked to Muscle Mitochondrial Distribution and Respiratory Function

PubMed Central

Milner, Derek J.; Mavroidis, Manolis; Weisleder, Noah; Capetanaki, Yassemi

2000-01-01

Ultrastructural studies have previously suggested potential association of intermediate filaments (IFs) with mitochondria. Thus, we have investigated mitochondrial distribution and function in muscle lacking the IF protein desmin. Immunostaining of skeletal muscle tissue sections, as well as histochemical staining for the mitochondrial marker enzymes cytochrome C oxidase and succinate dehydrogenase, demonstrate abnormal accumulation of subsarcolemmal clumps of mitochondria in predominantly slow twitch skeletal muscle of desmin-null mice. Ultrastructural observation of desmin-null cardiac muscle demonstrates in addition to clumping, extensive mitochondrial proliferation in a significant fraction of the myocytes, particularly after work overload. These alterations are frequently associated with swelling and degeneration of the mitochondrial matrix. Mitochondrial abnormalities can be detected very early, before other structural defects become obvious. To investigate related changes in mitochondrial function, we have analyzed ADP-stimulated respiration of isolated muscle mitochondria, and ADP-stimulated mitochondrial respiration in situ using saponin skinned muscle fibers. The in vitro maximal rates of respiration in isolated cardiac mitochondria from desmin-null and wild-type mice were similar. However, mitochondrial respiration in situ is significantly altered in desmin-null muscle. Both the maximal rate of ADP-stimulated oxygen consumption and the dissociation constant (K m) for ADP are significantly reduced in desmin-null cardiac and soleus muscle compared with controls. Respiratory parameters for desmin-null fast twitch gastrocnemius muscle were unaffected. Additionally, respiratory measurements in the presence of creatine indicate that coupling of creatine kinase and the adenine translocator is lost in desmin-null soleus muscle. This coupling is unaffected in cardiac muscle from desmin-null animals. All of these studies indicate that desmin IFs play a significant

Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A (calpainopathy)

PubMed Central

Kramerova, Irina; Ermolova, Natalia; Eskin, Ascia; Hevener, Andrea; Quehenberger, Oswald; Armando, Aaron M.; Haller, Ronald; Romain, Nadine; Nelson, Stanley F.; Spencer, Melissa J.

2016-01-01

Limb girdle muscular dystrophy 2A is due to loss-of-function mutations in the Calpain 3 (CAPN3) gene. Our previous data suggest that CAPN3 helps to maintain the integrity of the triad complex in skeletal muscle. In Capn3 knock-out mice (C3KO), Ca2+ release and Ca2+/calmodulin kinase II (CaMKII) signaling are attenuated. We hypothesized that calpainopathy may result from a failure to transmit loading-induced Ca2+-mediated signals, necessary to up-regulate expression of muscle adaptation genes. To test this hypothesis, we compared transcriptomes of muscles from wild type (WT) and C3KO mice subjected to endurance exercise. In WT mice, exercise induces a gene signature that includes myofibrillar, mitochondrial and oxidative lipid metabolism genes, necessary for muscle adaptation. C3KO muscles fail to activate the same gene signature. Furthermore, in agreement with the aberrant transcriptional profile, we observe a commensurate functional defect in lipid metabolism whereby C3KO muscles fail to release fatty acids from stored triacylglycerol. In conjunction with the defects in oxidative metabolism, C3KO mice demonstrate reduced exercise endurance. Failure to up-regulate genes in C3KO muscles is due, in part, to decreased levels of PGC1α, a transcriptional co-regulator that orchestrates the muscle adaptation response. Destabilization of PGC1α is attributable to decreased p38 MAPK activation via diminished CaMKII signaling. Thus, we elucidate a pathway downstream of Ca2+-mediated CaMKII activation that is dysfunctional in C3KO mice, leading to reduced transcription of genes involved in muscle adaptation. These studies identify a novel mechanism of muscular dystrophy: a blunted transcriptional response to muscle loading resulting in chronic failure to adapt and remodel. PMID:27005420

Electrophysiologic and functional evaluations of regenerated facial nerve defects with a tube containing dental pulp cells in rats.

PubMed

Sasaki, Ryo; Matsumine, Hajime; Watanabe, Yorikatsu; Takeuchi, Yuichi; Yamato, Masayuki; Okano, Teruo; Miyata, Mariko; Ando, Tomohiro

2014-11-01

Dental pulp tissue contains Schwann and neural progenitor cells. Tissue-engineered nerve conduits with dental pulp cells promote facial nerve regeneration in rats. However, no nerve functional or electrophysiologic evaluations were performed. This study investigated the compound muscle action potential recordings and facial functional analysis of dental pulp cell regenerated nerve in rats. A silicone tube containing rat dental pulp cells in type I collagen gel was transplanted into a 7-mm gap of the buccal branch of the facial nerve in Lewis rats; the same defect was created in the marginal mandibular branch, which was ligatured. Compound muscle action potential recordings of vibrissal muscles and facial functional analysis with facial palsy score of the nerve were performed. Tubulation with dental pulp cells showed significantly lower facial palsy scores than the autograft group between 3 and 10 weeks postoperatively. However, the dental pulp cell facial palsy scores showed no significant difference from those of autograft after 11 weeks. Amplitude and duration of compound muscle action potentials in the dental pulp cell group showed no significant difference from those of the intact and autograft groups, and there was no significant difference in the latency of compound muscle action potentials between the groups at 13 weeks postoperatively. However, the latency in the dental pulp cell group was prolonged more than that of the intact group. Tubulation with dental pulp cells could recover facial nerve defects functionally and electrophysiologically, and the recovery became comparable to that of nerve autografting in rats.

Optical redox imaging of fixed unstained tissue slides to identify biomarkers for breast cancer diagnosis/prognosis: feasibility study

NASA Astrophysics Data System (ADS)

Xu, He N.; Tchou, Julia; Li, Yusheng; Feng, Min; Zhang, Paul; Quinn, William J.; Baur, Joseph A.; Li, Lin Z.

2018-02-01

We previously showed that optical redox imaging (ORI) of snap-frozen breast biopsies by the Chance redox scanner readily discriminates cancer from normal tissue. Moreover, indices of redox heterogeneity differentiate among tumor xenografts with different metastatic potential. These observations suggest that ORI of fluorescence of NADH and oxidized flavoproteins (Fp) may provide diagnostic/prognostic value for clinical applications. In this work, we investigate whether ORI of formalin-fixed-paraffin-embedded (FFPE) unstained clinical tissue slides of breast tumors is feasible and comparable to ORI of snap-frozen tumors. If ORI of FFPE is validated, it will enhance the versatility of ORI as a novel diagnostic/prognostic assay as FFPE samples are readily available. ORI of fixed tissue slides was performed using a fluorescence microscope equipped with a precision automated stage and appropriate optical filters. We developed a vignette correction algorithm to remove the tiling effect of stitched-images. The preliminary data from imaging fixed slides of breast tumor xenografts showed intratumor redox heterogeneity patterns similar to that of the frozen tissues imaged by the Chance redox scanner. From ORI of human breast tissue slides we identified certain redox differences among normal, ductal carcinoma in situ, and invasive carcinoma. We found paraformaldehyde fixation causes no change in NADH signals but enhances Fp signals of fresh muscle fibers. We also investigated the stability of the fluorescence microscope and reproducibility of tissue slide fluorescence signals. We plan to validate the diagnostic/prognostic value of ORI using clinically annotated breast cancer sample set from patients with long-term follow-up data.

Drosophila melanogaster muscle LIM protein and alpha-actinin function together to stabilize muscle cytoarchitecture: a potential role for Mlp84B in actin-crosslinking.

PubMed

Clark, Kathleen A; Kadrmas, Julie L

2013-06-01

Stabilization of tissue architecture during development and growth is essential to maintain structural integrity. Because of its contractile nature, muscle is especially susceptible to physiological stresses, and has multiple mechanisms to maintain structural integrity. The Drosophila melanogaster Muscle LIM Protein (MLP), Mlp84B, participates in muscle maintenance, yet its precise mechanism of action is still controversial. Through a candidate approach, we identified α-actinin as a protein that functions with Mlp84B to ensure muscle integrity. α-actinin RNAi animals die primarily as pupae, and Mlp84B RNAi animals are adult viable. RNAi knockdown of Mlp84B and α-actinin together produces synergistic early larval lethality and destabilization of Z-line structures. We recapitulated these phenotypes using combinations of traditional loss-of-function alleles and single-gene RNAi. We observe that Mlp84B induces the formation of actin loops in muscle cell nuclei in the absence of nuclear α-actinin, suggesting Mlp84B has intrinsic actin cross-linking activity, which may complement α-actinin cross-linking activity at sites of actin filament anchorage. These results reveal a molecular mechanism for MLP stabilization of muscle and implicate reduced actin crosslinking as the primary destabilizing defect in MLP-associated cardiomyopathies. Our data support a model in which α-actinin and Mlp84B have important and overlapping functions at sites of actin filament anchorage to preserve muscle structure and function. Copyright © 2013 Wiley Periodicals, Inc.

A simplified surgical algorithm for flap reconstruction of eyebrow defects.

PubMed

Liu, Hai-Peng; Shao, Ying; Yu, Xiao-Jie; Zhang, Duo

2017-04-01

Partial or total eyebrow defects after trauma or tumor excisions have been repaired by several surgical technique and algorithms. However, these algorithms are often complicated and difficult to apply clinically. We therefore established a simplified surgical algorithm for the treatment of eyebrow defects using flap reconstruction. During the period between January 2009 and December 2015, a total of 21 Chinese patients (12 males, 9 females) with eyebrow defects were treated with eyebrow flap reconstruction. The ages ranged from 12 to 51 years. The patients included 13 cases located on the left and 8 cases on the right eyebrow. These defects were caused by trauma (5 patients) and tumor excision (16 patients). Among them, 6 patients were treated using superficial temporal artery island flap, while 15 patients were treated using the V-Y advancement pedicle flap based on the orbicularis oculi muscle. The minimum defect area was 0.8 × 1.0 cm and maximum area was 2.3 × 4.3 cm. All patients were followed up for 6 months to 5 years postoperatively. The clinical effects of eyebrow reconstruction were evaluated using a designated scoring system. All 21 flaps survived without significant complications and the shapes of the reconstructed eyebrows were continuous, symmetrical and with good integrity. According to the rating scale, there were 13 excellent, 8 good reconstructions among all patients. After an average of 9 months of follow-up, all patients had no recurrence of tumors and no infection or scarring. Based upon our experience with 21 patients who underwent eyebrow reconstruction for various eyebrow defects, we believe that our simplified surgical algorithm can serve as a model for the treatment of patients with eyebrow defects. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Mapping Interactions between Myosin Relay and Converter Domains That Power Muscle Function*

PubMed Central

Kronert, William A.; Melkani, Girish C.; Melkani, Anju; Bernstein, Sanford I.

2014-01-01

Intramolecular communication within myosin is essential for its function as motor, but the specific amino acid residue interactions required are unexplored within muscle cells. Using Drosophila melanogaster skeletal muscle myosin, we performed a novel in vivo molecular suppression analysis to define the importance of three relay loop amino acid residues (Ile508, Asn509, and Asp511) in communicating with converter domain residue Arg759. We found that the N509K relay mutation suppressed defects in myosin ATPase, in vitro motility, myofibril stability, and muscle function associated with the R759E converter mutation. Through molecular modeling, we define a mechanism for this interaction and suggest why the I508K and D511K relay mutations fail to suppress R759E. Interestingly, I508K disabled motor function and myofibril assembly, suggesting that productive relay-converter interaction is essential for both processes. We conclude that the putative relay-converter interaction mediated by myosin residues 509 and 759 is critical for the biochemical and biophysical function of skeletal muscle myosin and the normal ultrastructural and mechanical properties of muscle. PMID:24627474

Impaired mitochondrial oxidative phosphorylation and supercomplex assembly in rectus abdominis muscle of diabetic obese individuals.

PubMed

Antoun, Ghadi; McMurray, Fiona; Thrush, A Brianne; Patten, David A; Peixoto, Alyssa C; Slack, Ruth S; McPherson, Ruth; Dent, Robert; Harper, Mary-Ellen

2015-12-01

Skeletal muscle mitochondrial dysfunction has been documented in patients with type 2 diabetes mellitus; however, specific respiratory defects and their mechanisms are poorly understood. The aim of the current study was to examine oxidative phosphorylation and electron transport chain (ETC) supercomplex assembly in rectus abdominis muscles of 10 obese diabetic and 10 obese non-diabetic individuals. Twenty obese women undergoing Roux-en-Y gastric bypass surgery were recruited for this study. Muscle samples were obtained intraoperatively and subdivided for multiple analyses, including high-resolution respirometry and assessment of supercomplex assembly. Clinical data obtained from referring physicians were correlated with laboratory findings. Participants in both groups were of a similar age, weight and BMI. Mitochondrial respiration rates were markedly reduced in diabetic vs non-diabetic patients. This defect was observed during maximal ADP-stimulated respiration in the presence of complex I-linked substrates and complex I- and II-linked substrates, and during maximal uncoupled respiration. There were no differences in fatty acid (octanoyl carnitine) supported respiration, leak respiration or isolated activity of cytochrome c oxidase. Intriguingly, significant correlations were found between glycated haemoglobin (HbA1c) levels and maximal respiration or respiration supported by complex I, complex I and II or fatty acid. In the muscle of diabetic patients, blue native gel electrophoresis revealed a striking decrease in complex I, III and IV containing ETC supercomplexes. These findings support the hypothesis that ETC supercomplex assembly may be an important underlying mechanism of muscle mitochondrial dysfunction in type 2 diabetes mellitus.

Treatment of ischial pressure sores with both profunda femoris artery perforator flaps and muscle flaps.

PubMed

Kim, Chae Min; Yun, In Sik; Lee, Dong Won; Lew, Dae Hyun; Rah, Dong Kyun; Lee, Won Jai

2014-07-01

Reconstruction of ischial pressure sore defects is challenging due to extensive bursas and high recurrence rates. In this study, we simultaneously applied a muscle flap that covered the exposed ischium and large bursa with sufficient muscular volume and a profunda femoris artery perforator fasciocutaneous flap for the management of ischial pressure sores. We retrospectively analyzed data from 14 patients (16 ischial sores) whose ischial defects had been reconstructed using both a profunda femoris artery perforator flap and a muscle flap between January 2006 and February 2014. We compared patient characteristics, operative procedure, and clinical course. All flaps survived the entire follow-up period. Seven patients (50%) had a history of surgery at the site of the ischial pressure sore. The mean age of the patients included was 52.8 years (range, 18-85 years). The mean follow-up period was 27.9 months (range, 3-57 months). In two patients, a biceps femoris muscle flap was used, while a gracilis muscle flap was used in the remaining patients. In four cases (25%), wound dehiscence occurred, but healed without further complication after resuturing. Additionally, congestion occurred in one case (6%), but resolved with conservative treatment. Among 16 cases, there was only one (6%) recurrence at 34 months. The combination of a profunda femoris artery perforator fasciocutaneous flap and muscle flap for the treatment of ischial pressure sores provided pliability, adequate bulkiness and few long-term complications. Therefore, this may be used as an alternative treatment method for ischial pressure sores.

Treatment of Ischial Pressure Sores with Both Profunda Femoris Artery Perforator Flaps and Muscle Flaps

PubMed Central

Kim, Chae Min; Yun, In Sik; Lee, Dong Won; Lew, Dae Hyun; Rah, Dong Kyun

2014-01-01

Background Reconstruction of ischial pressure sore defects is challenging due to extensive bursas and high recurrence rates. In this study, we simultaneously applied a muscle flap that covered the exposed ischium and large bursa with sufficient muscular volume and a profunda femoris artery perforator fasciocutaneous flap for the management of ischial pressure sores. Methods We retrospectively analyzed data from 14 patients (16 ischial sores) whose ischial defects had been reconstructed using both a profunda femoris artery perforator flap and a muscle flap between January 2006 and February 2014. We compared patient characteristics, operative procedure, and clinical course. Results All flaps survived the entire follow-up period. Seven patients (50%) had a history of surgery at the site of the ischial pressure sore. The mean age of the patients included was 52.8 years (range, 18-85 years). The mean follow-up period was 27.9 months (range, 3-57 months). In two patients, a biceps femoris muscle flap was used, while a gracilis muscle flap was used in the remaining patients. In four cases (25%), wound dehiscence occurred, but healed without further complication after resuturing. Additionally, congestion occurred in one case (6%), but resolved with conservative treatment. Among 16 cases, there was only one (6%) recurrence at 34 months. Conclusions The combination of a profunda femoris artery perforator fasciocutaneous flap and muscle flap for the treatment of ischial pressure sores provided pliability, adequate bulkiness and few long-term complications. Therefore, this may be used as an alternative treatment method for ischial pressure sores. PMID:25075362

Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy

PubMed Central

Martin, Elizabeth A.; Barresi, Rita; Byrne, Barry J.; Tsimerinov, Evgeny I.; Scott, Bryan L.; Walker, Ashley E.; Gurudevan, Swaminatha V.; Anene, Francine; Elashoff, Robert M.; Thomas, Gail D.; Victor, Ronald G.

2013-01-01

Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin’s rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived nitric oxide (NO) attenuates local α-adrenergic vasoconstriction thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective—causing functional muscle ischemia—in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. Here, we report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled cross-over trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation fully restored in the muscles of men with BMD by boosting NO-cGMP signaling with a single dose of the drug tadalafil, a phosphodiesterase (PDE5A) inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD. PMID:23197572

Pathophysiology of Corneal Scarring in Persistent Epithelial Defects After PRK and Other Corneal Injuries.

PubMed

Wilson, Steven E; Medeiros, Carla S; Santhiago, Marcony R

2018-01-01

To analyze corneal persistent epithelial defects that occurred at 3 to 4 weeks after -4.50 diopter (D) photorefractive keratectomy (PRK) in rabbits and apply this pathophysiology to the treatment of persistent epithelial defects that occur after any corneal manipulations or diseases. Two of 168 corneas that had -4.50 D PRK to study epithelial basement membrane regeneration developed spontaneous persistent epithelial defects that did not heal at 3 weeks after PRK. These were studied with slit-lamp photographs, immunohistochemistry for the myofibroblast marker alpha-smooth muscle actin (α-SMA), and transmission electron microscopy. Myofibroblasts developed at the stromal surface within the persistent epithelial defect and for a short distance peripheral to the leading edge of the epithelium. No normal epithelial basement membrane was detectable within the persistent epithelial defect or for up to 0.3 mm behind the leading edge of the epithelium, although epithelial basement membrane had normally regenerated in other areas of the zone ablated by an excimer laser where the epithelium healed promptly. A persistent epithelial defect in the cornea results in the development of myofibroblasts and disordered extracellular matrix produced by these cells that together cause opacity within, and a short distance beyond, the persistent epithelial defect. Clinicians should treat persistent epithelial defects within 10 days of non-closure of the epithelium to facilitate epithelial healing to prevent long-term stromal scarring (fibrosis). [J Refract Surg. 2018;34(1):59-64.]. Copyright 2018, SLACK Incorporated.

Tissue engineering skeletal muscle for orthopaedic applications

NASA Technical Reports Server (NTRS)

Payumo, Francis C.; Kim, Hyun D.; Sherling, Michael A.; Smith, Lee P.; Powell, Courtney; Wang, Xiao; Keeping, Hugh S.; Valentini, Robert F.; Vandenburgh, Herman H.

2002-01-01

With current technology, tissue-engineered skeletal muscle analogues (bioartificial muscles) generate too little active force to be clinically useful in orthopaedic applications. They have been engineered genetically with numerous transgenes (growth hormone, insulinlike growth factor-1, erythropoietin, vascular endothelial growth factor), and have been shown to deliver these therapeutic proteins either locally or systemically for months in vivo. Bone morphogenetic proteins belonging to the transforming growth factor-beta superfamily are osteoinductive molecules that drive the differentiation pathway of mesenchymal cells toward the chondroblastic or osteoblastic lineage, and stimulate bone formation in vivo. To determine whether skeletal muscle cells endogenously expressing bone morphogenetic proteins might serve as a vehicle for systemic bone morphogenetic protein delivery in vivo, proliferating skeletal myoblasts (C2C12) were transduced with a replication defective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6). The C2BMP-6 cells constitutively expressed recombinant human bone morphogenetic protein-6 and synthesized bioactive recombinant human bone morphogenetic protein-6, based on increased alkaline phosphatase activity in coincubated mesenchymal cells. C2BMP-6 cells did not secrete soluble, bioactive recombinant human bone morphogenetic protein-6, but retained the bioactivity in the cell layer. Therefore, genetically-engineered skeletal muscle cells might serve as a platform for long-term delivery of osteoinductive bone morphogenetic proteins locally.

Orthogonal muscle fibres have different instructive roles in planarian regeneration.

PubMed

Scimone, M Lucila; Cote, Lauren E; Reddien, Peter W

2017-11-30

The ability to regenerate missing body parts exists throughout the animal kingdom. Positional information is crucial for regeneration, but how it is harboured and used by differentiated tissues is poorly understood. In planarians, positional information has been identified from study of phenotypes caused by RNA interference in which the wrong tissues are regenerated. For example, inhibition of the Wnt signalling pathway leads to regeneration of heads in place of tails. Characterization of these phenotypes has led to the identification of position control genes (PCGs)-genes that are expressed in a constitutive and regional manner and are associated with patterning. Most PCGs are expressed within planarian muscle; however, how muscle is specified and how different muscle subsets affect regeneration is unknown. Here we show that different muscle fibres have distinct regulatory roles during regeneration in the planarian Schmidtea mediterranea. myoD is required for formation of a specific muscle cell subset: the longitudinal fibres, oriented along the anterior-posterior axis. Loss of longitudinal fibres led to complete regeneration failure because of defects in regeneration initiation. A different transcription factor-encoding gene, nkx1-1, is required for the formation of circular fibres, oriented along the medial-lateral axis. Loss of circular fibres led to a bifurcated anterior-posterior axis with fused heads forming in single anterior blastemas. Whereas muscle is often viewed as a strictly contractile tissue, these findings reveal that different muscle types have distinct and specific regulatory roles in wound signalling and patterning to enable regeneration.

Muscle Deoxygenation Causes Muscle Fatigue

NASA Technical Reports Server (NTRS)

Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D.

1999-01-01

Muscle fatigue is a common musculoskeletal disorder in the work place, and may be a harbinger for more disabling cumulative trauma disorders. Although the cause of fatigue is multifactorial, reduced blood flow and muscle oxygenation may be the primary factor in causing muscle fatigue during low intensity muscle exertion. Muscle fatigue is defined as a reduction in muscle force production, and also occurs among astronauts who are subjected to postural constraints while performing lengthy, repetitive tasks. The objectives of this research are to: 1) develop an objective tool to study the role of decreased muscle oxygenation on muscle force production, and 2) to evaluate muscle fatigue during prolonged glovebox work.

Monitoring Autophagy in Muscle Stem Cells.

PubMed

García-Prat, Laura; Muñoz-Cánoves, Pura; Martínez-Vicente, Marta

2017-01-01

Autophagy is critical not only for the cell's adaptive response to starvation but also for cellular homeostasis, by acting as quality-control machinery for cytoplasmic components. This basal autophagic activity is particularly needed in postmitotic cells for survival maintenance. Recently, basal autophagic activity was reported in skeletal muscle stem cells (satellite cells) in their dormant quiescent state. Satellite cells are responsible for growth as well as for regeneration of muscle in response to stresses such as injury or disease. In the absence of stress, quiescence is the stem cell state of these cells throughout life, although which mechanisms maintain long-life quiescence remains largely unknown. Our recent findings showed that autophagy is necessary for quiescence maintenance in satellite cells and for retention of their regenerative functions. Importantly, damaged organelles and proteins accumulated in these cells with aging and this was connected to age-associated defective autophagy. Refueling of autophagy through genetic and pharmacological strategies restored aged satellite cell functions, and these finding have biomedical implications. In this chapter, we describe different experimental strategies to evaluate autophagic activity in satellite cells in resting muscle of mice. They should facilitate our competence to investigate stem cell functions both during tissue homeostasis as in pathological conditions.

ELECTROMYOGRAPHIC EVALUATION OF MASTICATION AND SWALLOWING IN ELDERLY INDIVIDUALS WITH MANDIBULAR FIXED IMPLANTSUPPORTED PROSTHESES

PubMed Central

Berretin-Felix, Giédre; Nary, Hugo; Padovani, Carlos Roberto; Trindade, Alceu Sergio; Machado, Wellington Monteiro

2008-01-01

This study evaluated the effect of implant-supported oral rehabilitation in the mandible on the electromyographic activity during mastication and swallowing in edentulous elderly individuals. Fifteen patients aged more than 60 years were evaluated, being 10 females and 5 males. All patients were edentulous, wore removable complete dentures on both dental arches, and had the mandibular dentures replaced by implant-supported prostheses. All patients were submitted to electromyographic evaluation of the masseter, superior orbicularis oris muscles, and the submental muscles, before surgery and 3, 6 and 18 months postoperatively, using foods of different textures. The results obtained at the different periods were analyzed statistically by Kruskal-Wallis non-parametric test. Statistical analysis showed that only the masseter muscle had a significant loss in electromyographic activity (p<0.001), with a tendency of similar response for the submental muscles. Moreover, there was an increase in the activity of the orbicularis oris muscle during rubber chewing after treatment, yet without statistically significant difference. Mandibular fixed implant-supported prostheses in elderly individuals revealed a decrease in electromyographic amplitude for the masseter muscles during swallowing, which may indicate adaptation to new conditions of stability provided by fixation of the complete denture in the mandibular arch. PMID:19089202

Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting

NASA Technical Reports Server (NTRS)

Wing, S. S.; Goldberg, A. L.; Goldberger, A. L. (Principal Investigator)

1993-01-01

Glucocorticoids are essential for the increase in protein breakdown in skeletal muscle normally seen during fasting. To determine which proteolytic pathway(s) are activated upon fasting, leg muscles from fed and fasted normal rats were incubated under conditions that block or activate different proteolytic systems. After food deprivation (1 day), the nonlysosomal ATP-dependent process increased by 250%, as shown in experiments involving depletion of muscle ATP. Also, the maximal capacity of the lysosomal process increased 60-100%, but no changes occurred in the Ca(2+)-dependent or the residual energy-independent proteolytic processes. In muscles from fasted normal and adrenalectomized (ADX) rats, the protein breakdown sensitive to inhibitors of the lysosomal or Ca(2+)-dependent pathways did not differ. However, the ATP-dependent process was 30% slower in muscles from fasted ADX rats. Administering dexamethasone to these animals or incubating their muscles with dexamethasone reversed this defect. During fasting, when the ATP-dependent process rises, muscles show a two- to threefold increase in levels of ubiquitin (Ub) mRNA. However, muscles of ADX animals failed to show this response. Injecting dexamethasone into the fasted ADX animals increased muscle Ub mRNA within 6 h. Thus glucocorticoids activate the ATP-Ub-dependent proteolytic pathway in fasting apparently by enhancing the expression of components of this system such as Ub.

The Actinomyces oris Type 2 Fimbrial Shaft FimA Mediates Coaggregation with Oral Streptococci, Adherence to RBC and Biofilm Development

PubMed Central

Mishra, Arunima; Wu, Chenggang; Yang, Jinghua; Cisar, John O.; Das, Asis; Ton-That, Hung

2010-01-01

Interbacterial interactions between oral streptococci and actinomyces and their adherence to tooth surface and the associated host cells are key early events that promote development of the complex oral biofilm referred to as dental plaque. These interactions depend largely on a lectin-like activity associated with the Actinomyces oris type 2 fimbria, a surface structure assembled by sortase (SrtC2)-dependent polymerization of the shaft and tip fimbrillins, FimA and FimB, respectively. To dissect the function of specific fimbrillins in various adherence processes, we have developed a convenient new technology for generating unmarked deletion mutants of A. oris. Here, we show that the fimB mutant, which produced type 2 fimbriae composed only of FimA, like the wild type coaggregated strongly with receptor-bearing streptococci, agglutinated with sialidase-treated RBC, and formed monospecies biofilm. In contrast, the fimA and srtC2 mutants lacked type 2 fimbriae and were non-adherent in each of these assays. Plasmidbased expression of the deleted gene in respective mutants restored adherence to wild-type levels. These findings uncover the importance of the lectin-like activity of the polymeric FimA shaft rather than the tip. The multivalent adhesive function of FimA makes it an ideal molecule for exploring novel intervention strategies to control plaque biofilm formation. PMID:20545853

Zebrafish embryos exposed to alcohol undergo abnormal development of motor neurons and muscle fibers.

PubMed

Sylvain, Nicole J; Brewster, Daniel L; Ali, Declan W

2010-01-01

Children exposed to alcohol in utero have significantly delayed gross and fine motor skills, as well as deficiencies in reflex development. The reasons that underlie the motor deficits caused by ethanol (EtOH) exposure remain to be fully elucidated. The present study was undertaken to investigate the effects of embryonic alcohol exposure (1.5%, 2% and 2.5% EtOH) on motor neuron and muscle fiber morphology in 3 days post fertilization (dpf) larval zebrafish. EtOH treated fish exhibited morphological deformities and fewer bouts of swimming in response to touch, compared with untreated fish. Immunolabelling with anti-acetylated tubulin indicated that fish exposed to 2.5% EtOH had significantly higher rates of motor neuron axon defects. Immunolabelling of primary and secondary motor neurons, using znp-1 and zn-8, revealed that fish exposed to 2% and 2.5% EtOH exhibited significantly higher rates of primary and secondary motor neuron axon defects compared to controls. Examination of red and white muscle fibers revealed that fish exposed to EtOH had significantly smaller fibers compared with controls. These findings indicate that motor neuron and muscle fiber morphology is affected by early alcohol exposure in zebrafish embryos, and that this may be related to deficits in locomotion. Copyright 2010 Elsevier Inc. All rights reserved.

Low anaerobic threshold and increased skeletal muscle lactate production in subjects with Huntington's disease.

PubMed

Ciammola, Andrea; Sassone, Jenny; Sciacco, Monica; Mencacci, Niccolò E; Ripolone, Michela; Bizzi, Caterina; Colciago, Clarissa; Moggio, Maurizio; Parati, Gianfranco; Silani, Vincenzo; Malfatto, Gabriella

2011-01-01

Mitochondrial defects that affect cellular energy metabolism have long been implicated in the etiology of Huntington's disease (HD). Indeed, several studies have found defects in the mitochondrial functions of the central nervous system and peripheral tissues of HD patients. In this study, we investigated the in vivo oxidative metabolism of exercising muscle in HD patients. Ventilatory and cardiometabolic parameters and plasma lactate concentrations were monitored during incremental cardiopulmonary exercise in twenty-five HD subjects and twenty-five healthy subjects. The total exercise capacity was normal in HD subjects but notably the HD patients and presymptomatic mutation carriers had a lower anaerobic threshold than the control subjects. The low anaerobic threshold of HD patients was associated with an increase in the concentration of plasma lactate. We also analyzed in vitro muscular cell cultures and found that HD cells produce more lactate than the cells of healthy subjects. Finally, we analyzed skeletal muscle samples by electron microscopy and we observed striking mitochondrial structural abnormalities in two out of seven HD subjects. Our findings confirm mitochondrial abnormalities in HD patients' skeletal muscle and suggest that the mitochondrial dysfunction is reflected functionally in a low anaerobic threshold and an increased lactate synthesis during intense physical exercise. Copyright © 2010 Movement Disorder Society.

Exertional rhabdomyolysis leading to acute kidney injury: when genetic defects are diagnosed in adult life.

PubMed

Cucchiari, David; Colombo, Irene; Amato, Ottavia; Podestà, Manuel Alfredo; Reggiani, Francesco; Valentino, Rossella; Faravelli, Irene; Testolin, Silvia; Moggio, Maurizio; Badalamenti, Salvatore

2018-05-01

Rhabdomyolysis is a common cause of acute kidney injury (AKI) that is usually triggered by trauma. However, less common causes of rhabdomyolysis may precipitate AKI as well, possibly representing a diagnostic challenge even for the experienced nephrologist. Genetic defects of muscle metabolism represent one of these causes and can be overlooked in adults, since these diseases usually become apparent in childhood. We present here a case in which an adult patient with severe exertional rhabdomyolysis leading to AKI was finally diagnosed with a genetic defect of lipid metabolism. A 41-year-old patient was brought to our attention because of AKI and pigmenturia after strenuous physical effort. At admission, the patient was over-hydrated with a weight increase of 3 kg in few days. Laboratory examination showed creatinine of 8.7 mg/dl, along with increased myoglobin and CPK. Urinalysis was positive for haemoglobin and proteins, while urinary sediment analysis did not demonstrate any red blood cell but rather "muddy-brown" casts and tubular cells. Urine output was forced and the patient completely recovered renal function. Genetic analysis later demonstrated the presence of a common mutation of Carnitine Palmitoyl-Transferase II (CPTII). When facing rhabdomyolysis of obscure origin, nephrologists must keep in mind the possibility that even adult patients may have a genetic defect of energy metabolism. In these cases, patients usually experience rhabdomyolysis during exertion, fasting, or infection. CPTII deficiency often has a subtle presentation and might be unrecognized until AKI develops. Therefore, it is important to consider a genetic defect of muscle metabolism even in adult patients when a history of rhabdomyolysis of unclear origin is present.

Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease

PubMed Central

Nsiah-Sefaa, Abena; McKenzie, Matthew

2016-01-01

Mitochondria provide the main source of energy to eukaryotic cells, oxidizing fats and sugars to generate ATP. Mitochondrial fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are two metabolic pathways which are central to this process. Defects in these pathways can result in diseases of the brain, skeletal muscle, heart and liver, affecting approximately 1 in 5000 live births. There are no effective therapies for these disorders, with quality of life severely reduced for most patients. The pathology underlying many aspects of these diseases is not well understood; for example, it is not clear why some patients with primary FAO deficiencies exhibit secondary OXPHOS defects. However, recent findings suggest that physical interactions exist between FAO and OXPHOS proteins, and that these interactions are critical for both FAO and OXPHOS function. Here, we review our current understanding of the interactions between FAO and OXPHOS proteins and how defects in these two metabolic pathways contribute to mitochondrial disease pathogenesis. PMID:26839416

Lack of Glycogenin Causes Glycogen Accumulation and Muscle Function Impairment.

PubMed

Testoni, Giorgia; Duran, Jordi; García-Rocha, Mar; Vilaplana, Francisco; Serrano, Antonio L; Sebastián, David; López-Soldado, Iliana; Sullivan, Mitchell A; Slebe, Felipe; Vilaseca, Marta; Muñoz-Cánoves, Pura; Guinovart, Joan J

2017-07-05

Glycogenin is considered essential for glycogen synthesis, as it acts as a primer for the initiation of the polysaccharide chain. Against expectations, glycogenin-deficient mice (Gyg KO) accumulate high amounts of glycogen in striated muscle. Furthermore, this glycogen contains no covalently bound protein, thereby demonstrating that a protein primer is not strictly necessary for the synthesis of the polysaccharide in vivo. Strikingly, in spite of the higher glycogen content, Gyg KO mice showed lower resting energy expenditure and less resistance than control animals when subjected to endurance exercise. These observations can be attributed to a switch of oxidative myofibers toward glycolytic metabolism. Mice overexpressing glycogen synthase in the muscle showed similar alterations, thus indicating that this switch is caused by the excess of glycogen. These results may explain the muscular defects of GSD XV patients, who lack glycogenin-1 and show high glycogen accumulation in muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

Birth Defects

MedlinePlus

... both. Some birth defects like cleft lip or neural tube defects are structural problems that can be ... during pregnancy is a key factor in causing neural tube defects. For most birth defects, the cause ...

Ultrastructural findings in lung biopsy material from children with congenital heart defects.

PubMed Central

Meyrick, B.; Reid, L.

1980-01-01

The ultrastructural features of pulmonary arteries are described in lung biopsy material from 6 children with congenital heart defects. Right ventricular hypertrophy was found in all 6 children and increased pulmonary artery pressure in all but one. The presence of muscle in smaller and more peripheral arteries than expected for the age of the child was detected in all cases. Ultrastructural examination of the peripheral arteries revealed, for the first time, in the nonmuscular regions of human arterial walls, pericytes and intermediate cells (previously shown to be precursor smooth-muscle cells); in addition, new arterial muscle was found in the normally nonmuscular region. In the 4 cases where medial thickness of the normally muscular arteries was increased, the smooth-muscle cells were hypertrophied and the extracellular connective tissue increased. In all cases, junctions between endothelial cells and smooth-muscle cells, intermediate cells, or pericytes were found. These changes are similar to those described in the rat with hypoxia-induced pulmonary hypertension. In addition, in 2 of the 6 cases, bundles of nerve axons in Schwann cell sheaths were found in adventitial layer of small, intraacinar muscular arteries (not previously demonstrated ultrastructurally at this site in the human lung); varicosities with agranular and granular vesicles, probably adrenergic, were also identified. Images Figure 4 Figure 5 Figure 1 Figure 2 Figure 3 PMID:7446706

Direct Interferometric Imaging with IOTA Interferometer: Morphology of the Water Shell around U Ori

NASA Astrophysics Data System (ADS)

Pluzhnik, Eugene; Ragland, S.; Le Coroller, H.; Cotton, W.; Danchi, W.; Traub, W.; Willson, L.

2007-12-01

Optical interferometric observations of Mira stars with adequate resolution using the 3-telescope Infrared Optical Telescope Array (IOTA) interferometer have shown detectable asymmetry in several Mira stars. Several mechanisms have been proposed to explain the observed asymmetry. In this paper, we present subsequent IOTA observations of a Mira star, namely, U Ori taken at 1.51, 1.64 and 1.78 μm in 2005. The reconstructed images based on a model independent algorithm are also presented. These images show asymmetric structures of the water shell that is similar to the structure of 22 GHz masers obtained by Vlemmings et al. in 2003. We explore the possibility of the detection of molecular shell rotation with a period of about 30 years by comparing our results with radio observations and discuss a possible geometric structure of the shell.

Scanning electron microscope automatic defect classification of process induced defects

NASA Astrophysics Data System (ADS)

Wolfe, Scott; McGarvey, Steve

2017-03-01

With the integration of high speed Scanning Electron Microscope (SEM) based Automated Defect Redetection (ADR) in both high volume semiconductor manufacturing and Research and Development (R and D), the need for reliable SEM Automated Defect Classification (ADC) has grown tremendously in the past few years. In many high volume manufacturing facilities and R and D operations, defect inspection is performed on EBeam (EB), Bright Field (BF) or Dark Field (DF) defect inspection equipment. A comma separated value (CSV) file is created by both the patterned and non-patterned defect inspection tools. The defect inspection result file contains a list of the inspection anomalies detected during the inspection tools' examination of each structure, or the examination of an entire wafers surface for non-patterned applications. This file is imported into the Defect Review Scanning Electron Microscope (DRSEM). Following the defect inspection result file import, the DRSEM automatically moves the wafer to each defect coordinate and performs ADR. During ADR the DRSEM operates in a reference mode, capturing a SEM image at the exact position of the anomalies coordinates and capturing a SEM image of a reference location in the center of the wafer. A Defect reference image is created based on the Reference image minus the Defect image. The exact coordinates of the defect is calculated based on the calculated defect position and the anomalies stage coordinate calculated when the high magnification SEM defect image is captured. The captured SEM image is processed through either DRSEM ADC binning, exporting to a Yield Analysis System (YAS), or a combination of both. Process Engineers, Yield Analysis Engineers or Failure Analysis Engineers will manually review the captured images to insure that either the YAS defect binning is accurately classifying the defects or that the DRSEM defect binning is accurately classifying the defects. This paper is an exploration of the feasibility of the

Reconstruction of midfoot bone and soft tissue loss with chimeric partial scapula and latissimus dorsi muscle flap and short perforator-based skin flap following gunshot injuries: Report of two cases.

PubMed

Ozcan Akcal, Arzu; Ünal, Kerim; Gorgulu, Tahsin; Akif Akcal, Mehmet; Bigat, Zekiye

2016-10-01

In this report we present two cases of gunshot injury related midfoot defects, reconstructed with a chimeric partial scapula and latissimus dorsi muscle flap and short perforator-based skin flap. The first case, a 14 years old male, had 10 × 8 cm medial plantar and 6 × 4 cm dorsal foot defects and the second case, a 55 years old female, had only 8 × 6 cm dorsal foot defect. In both cases the defects were associated with fractures, one with lateral cuneiform and cuboid with 90% bone loss and the other with navicular bone, respectively. After 6 months, the patients could walk well without support, and radiographs confirmed bony union. A chimeric partial scapula and latissimus dorsi muscle flap and short perforator-based skin flap may be used for the reconstruction of combined bony and soft tissue defects of the midfoot and to promote bone healing. © 2016 Wiley Periodicals, Inc. Microsurgery 36:598-603, 2016. © 2016 Wiley Periodicals, Inc.

Losartan administration reduces fibrosis but hinders functional recovery after volumetric muscle loss injury.

PubMed

Garg, Koyal; Corona, Benjamin T; Walters, Thomas J

2014-11-15

Losartan is a Food and Drug Administration approved antihypertensive medication that is recently emerging as an antifibrotic therapy. Previously, losartan has been successfully used to reduce fibrosis and improve both muscle regeneration and function in several models of recoverable skeletal muscle injuries, such as contusion and laceration. In this study, the efficacy of losartan treatment in reducing fibrosis and improving regeneration was determined in a Lewis rat model of volumetric muscle loss (VML) injury. VML has been defined as the traumatic or surgical loss of skeletal muscle with resultant functional impairment. It is among the top 10 causes for wounded service members to be medically retired from the military. This study shows that, after several weeks of recovery, VML injury results in little to no muscle regeneration, but is marked by persistent inflammation, chronic upregulation of profibrotic markers and extracellular matrix (i.e., collagen type I), and fat deposition at the defect site, which manifest irrecoverable deficits in force production. Losartan administration at 10 mg·kg(-1)·day(-1) was able to modulate the gene expression of fibrotic markers and was also effective at reducing fibrosis (i.e., the deposition of collagen type I) in the injured muscle. However, there were no improvements in muscle regeneration, and deleterious effects on muscle function were observed instead. We propose that, in the absence of regeneration, reduction in fibrosis worsens the ability of the VML injured muscle to transmit forces, which ultimately results in decreased muscle function.

[BIPADDLED SPLIT PECTORALIS MAJOR MYOCUTANEOUS FLAPS FOR IMMEDIATE RECONSTRUCTION OF ORAL MUCOSAL DEFECTS AND NECK DEFECTS AFTER RESECTION OF RECURRENT ORAL CANCER].

PubMed

Chen, Jie; Jiang, Canhua; Li, Ning; Gao, Zhengyang; Chen, Lichun; Wu, Xiaoshan; Chen, Xinqun; Jian, Xinchun

2015-07-01

To investigate the feasibility of the bipaddled split pectoralis major myocutaneous flap for immediate reconstruction of oral mucosal defects and neck defects after resection of recurrent oral cancer. Six patients with oral mucosal defects combined with neck defects after recurrent oral cancer resection were treated with bipaddled split pectoralis major myocutaneous flap between September 2013 and September 2014. There were 5 males and 1 female with an average age of 54.7 years (range, 45-62 years), including 4 cases of recurrent tongue cancer, 1 case of recurrent mandibular gingival cancer, and 1 case of mouth floor carcinoma. All patients underwent local recurrence at 8 to 14 months after first operation, with no distant metastasis. The defects of the intraoral mucosa was 4.0 cm x 2.5 cm to 6.5 cm x 3.5 cm and the defect of the neck skin was 5.5 cm x 3.5 cm to 7.5 cm x 5.0 cm. The pectoralis major myocutaneous flaps (14.0 cm x 3.5 cm to 17.0 cm x 5.5 cm) were incised at the level of the 3rd to the 4th rib, and then split down along the muscle fiber till about 2 cm away from the thoracoacromial vessels, forming 2 independent skin paddles with 1-2 branch vessels to the pedicles of the distal ones. The distal skin paddles were used for oral reconstruction while the proximal paddles for repair of neck defects. The chest donor sites were sutured directly. Cervical haematoma and infection happened in 1 patient respectively after operation, and were cured after symptomatic treatment. All 6 split pectoralis major myocutaneous flaps with 12 skin paddles completely survived. All patients were followed up 6 to 18 months (mean, 11 months). One patient died of pulmonary metastasis at 8 months after operation and the other 5 survived without relapse or metastasis during follow-up. The intraoral paddles showed good shape with satisfactory speech function and swallowing recovery. The paddles also healed perfectly on the neck with flat outlooks, and all patients obtained full

Proteome-wide Adaptations of Mouse Skeletal Muscles during a Full Month in Space.

PubMed

Tascher, Georg; Brioche, Thomas; Maes, Pauline; Chopard, Angèle; O'Gorman, Donal; Gauquelin-Koch, Guillemette; Blanc, Stéphane; Bertile, Fabrice

2017-07-07

The safety of space flight is challenged by a severe loss of skeletal muscle mass, strength, and endurance that may compromise the health and performance of astronauts. The molecular mechanisms underpinning muscle atrophy and decreased performance have been studied mostly after short duration flights and are still not fully elucidated. By deciphering the muscle proteome changes elicited in mice after a full month aboard the BION-M1 biosatellite, we observed that the antigravity soleus incurred the greatest changes compared with locomotor muscles. Proteomics data notably suggested mitochondrial dysfunction, metabolic and fiber type switching toward glycolytic type II fibers, structural alterations, and calcium signaling-related defects to be the main causes for decreased muscle performance in flown mice. Alterations of the protein balance, mTOR pathway, myogenesis, and apoptosis were expected to contribute to muscle atrophy. Moreover, several signs reflecting alteration of telomere maintenance, oxidative stress, and insulin resistance were found as possible additional deleterious effects. Finally, 8 days of recovery post flight were not sufficient to restore completely flight-induced changes. Thus in-depth proteomics analysis unraveled the complex and multifactorial remodeling of skeletal muscle structure and function during long-term space flight, which should help define combined sets of countermeasures before, during, and after the flight.

Restricting calcium currents is required for correct fiber type specification in skeletal muscle