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https://www.readbyqxmd.com/read/28714082/in-situ-macrophage-phenotypic-transition-is-affected-by-altered-cellular-composition-prior-to-acute-sterile-muscle-injury
#1
Andreas Patsalos, Attila Pap, Tamas Varga, Gyorgy Trencsenyi, Gerardo Alvarado Contreras, Ildiko Garai, Zoltan Papp, Balazs Dezso, Eva Pintye, Laszlo Nagy
Skeletal muscle regeneration is a complex interplay between various cell types including invading macrophages. Their recruitment to damaged tissues upon acute sterile injuries is necessary for necrotic debris clearance and for coordination of tissue regeneration. This highly dynamic process is characterized by an in-situ transition of infiltrating monocytes from an inflammatory (Ly6C(high) ) to a repair (Ly6C(low) ) macrophage phenotype. The importance of the macrophage phenotypic shift and the cross-talk of the local muscle tissue with the infiltrating macrophages during tissue regeneration upon injury are not fully understood and their study lacks adequate methodology...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28700649/autophagy-mediates-cell-cycle-response-by-regulating-nucleocytoplasmic-transport-of-pax6-in-limbal-stem-cells-under-ultraviolet-a-stress
#2
Maria Laggner, Andreas Pollreisz, Gerald Schmidinger, Ursula Schmidt-Erfurth, Ying-Ting Chen
Limbal stem cells (LSC) account for homeostasis and regeneration of corneal epithelium. Solar ultraviolet A (UVA) is the major source causing oxidative damage in the ocular surface. Autophagy, a lysosomal degradation mechanism, is essential for physiologic function and stress defense of stem cells. PAX6, a master transcription factor governing corneal homeostasis by regulating cell cycle and cell fate of LSC, responds to oxidative stress by nucleocytoplasmic shuttling. Impaired autophagy and deregulated PAX6 have been reported in oxidative stress-related ocular surface disorders...
2017: PloS One
https://www.readbyqxmd.com/read/28693603/differential-requirement-for-satellite-cells-during-overload-induced-muscle-hypertrophy-in-growing-versus-mature-mice
#3
Kevin A Murach, Sarah H White, Yuan Wen, Angel Ho, Esther E Dupont-Versteegden, John J McCarthy, Charlotte A Peterson
BACKGROUND: Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age. METHODS: Pax7(CreER)-R26R(DTA) mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age...
July 10, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28689354/functional-and-molecular-characterization-of-a-novel-traumatic-peripheral-nerve-muscle-injury-model
#4
Renate Wanner, Manuel Gey, Alireza Abaei, Daniela Warnecke, Luisa de Roy, Lutz Dürselen, Volker Rasche, Bernd Knöll
Traumatic injuries to human peripheral nerves are frequently associated with damage to nerve surrounding tissues including muscles and blood vessels. Currently, most rodent models of peripheral nerve injuries (e.g., facial or sciatic nerve) employ surgical nerve transection with scissors or scalpels. However, such an isolated surgical nerve injury only mildly damages neighboring tissues and weakly activates an immune response. In order to provide a rodent nerve injury model accounting for such nerve-associated tissue damage and immune cell activation, we developed a drop tower-based facial nerve trauma model in mice...
July 8, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28676130/skeletal-muscle-derived-interstitial-progenitor-cells-pics-display-stem-cell-properties-being-clonogenic-self-renewing-and-multi-potent-in-vitro-and-in-vivo
#5
Beverley J Cottle, Fiona C Lewis, Victoria Shone, Georgina M Ellison-Hughes
BACKGROUND: The development of cellular therapies to treat muscle wastage with disease or age is paramount. Resident muscle satellite cells are not currently regarded as a viable cell source due to their limited migration and growth capability ex vivo. This study investigated the potential of muscle-derived PW1(+)/Pax7(-) interstitial progenitor cells (PICs) as a source of tissue-specific stem/progenitor cells with stem cell properties and multipotency. METHODS: Sca-1(+)/PW1(+) PICs were identified on tissue sections from hind limb muscle of 21-day-old mice, isolated by magnetic-activated cell sorting (MACS) technology and their phenotype and characteristics assessed over time in culture...
July 4, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28662356/a-population-based-study-of-effects-of-genetic-loci-on-orofacial-clefts
#6
L M Moreno Uribe, T Fomina, R G Munger, P A Romitti, M M Jenkins, H K Gjessing, M Gjerdevik, K Christensen, A J Wilcox, J C Murray, R T Lie, G L Wehby
Prior genome-wide association studies for oral clefts have focused on clinic-based samples with unclear generalizability. Prior samples were also small for investigating effects by cleft type and exclusively studied isolated clefts (those occurring without other birth defects). We estimated the effects of 17 top loci on cleft types in both isolated and nonisolated cases in the largest consortium to date of European-descent population-based studies. Our analytic approach focused on a mother-child dyad case-control design, but it also allowed analyzing mother-only or child-only genotypes to maximize power...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28658631/pax7-targets-cd54-integrin-%C3%AE-9%C3%AE-1-and-sdc2-allow-isolation-of-human-esc-ipsc-derived-myogenic-progenitors
#7
Alessandro Magli, Tania Incitti, James Kiley, Scott A Swanson, Radbod Darabi, Fabrizio Rinaldi, Sridhar Selvaraj, Ami Yamamoto, Jakub Tolar, Ce Yuan, Ron Stewart, James A Thomson, Rita C R Perlingeiro
Pluripotent stem (PS)-cell-derived cell types hold promise for treating degenerative diseases. However, PS cell differentiation is intrinsically heterogeneous; therefore, clinical translation requires the development of practical methods for isolating progenitors from unwanted and potentially teratogenic cells. Muscle-regenerating progenitors can be derived through transient PAX7 expression. To better understand the biology, and to discover potential markers for these cells, here we investigate PAX7 genomic targets and transcriptional changes in human cells undergoing PAX7-mediated myogenic commitment...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28643791/ewsr1-fusion-proteins-mediate-pax7-expression-in-ewing-sarcoma
#8
Gregory W Charville, Wei-Lien Wang, Davis R Ingram, Angshumoy Roy, Dafydd Thomas, Rajiv M Patel, Jason L Hornick, Matt van de Rijn, Alexander J Lazar
PAX7 is a paired-box transcription factor that is required for the developmental specification of adult skeletal muscle progenitors in mice. We previously demonstrated PAX7 expression as a marker of skeletal muscle differentiation in rhabdomyosarcoma. Here, using analyses of published whole-genome gene expression microarray data, we identify PAX7 as a gene with significantly increased expression in Ewing sarcoma in comparison to CIC-DUX4 round cell sarcoma. Analysis of PAX7 in a large cohort of 103 Ewing sarcoma cases by immunohistochemistry revealed expression in 99...
June 23, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28637492/expression-patterns-of-fshd-causing-dux4-and-myogenic-transcription-factors-pax3-and-pax7-are-spatially-distinct-in-differentiating-human-stem-cell-cultures
#9
Premi Haynes, Kelly Kernan, Suk-Lin Zhou, Daniel G Miller
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is most commonly inherited in an autosomal dominant pattern and caused by the abnormal expression of DUX4 in skeletal muscle. The DUX4 transcription factor has DNA binding domains similar to several paired class homeotic transcription factors, but only myogenic factors PAX3 and PAX7 rescue cell viability when co-expressed with DUX4 in mouse myoblasts. This observation suggests competition for DNA binding sites in satellite cells might limit muscle repair and may be one aspect of DUX4-associated myotoxicity...
June 21, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28625870/pax3-and-pax7-mediated-dbx1-regulation-orchestrates-the-patterning-of-intermediate-spinal-interneurons
#10
Chris Gard, Gloria Gonzalez Curto, Youcef El-Mokhtar Frarma, Elodie Chollet, Nathalie Duval, Valentine Auzié, Frédéric Auradé, Lisa Vigier, Frédéric Relaix, Alessandra Pierani, Frédéric Causeret, Vanessa Ribes
Transcription factors are key orchestrators of the emergence of neuronal diversity within the developing spinal cord. As such, the two paralogous proteins Pax3 and Pax7 regulate the specification of progenitor cells within the intermediate neural tube, by defining a neat segregation between those fated to form motor circuits and those involved in the integration of sensory inputs. To attain insights into the molecular means by which they control this process, we have performed detailed phenotypic analyses of the intermediate spinal interneurons (IN), namely the dI6, V0D, V0VCG and V1 populations in compound null mutants for Pax3 and Pax7...
June 16, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28615691/human-myogenic-reserve-cells-are-quiescent-stem-cells-that-contribute-to-muscle-regeneration-after-intramuscular-transplantation-in-immunodeficient-mice
#11
Thomas Laumonier, Flavien Bermont, Pierre Hoffmeyer, Vincent Kindler, Jacques Menetrey
Satellite cells, localized within muscles in vivo, are Pax7(+) muscle stem cells supporting skeletal muscle growth and regeneration. Unfortunately, their amplification in vitro, required for their therapeutic use, is associated with reduced regenerative potential. In the present study, we investigated if human myogenic reserve cells (MRC) obtained in vitro, represented a reliable cell source for muscle repair. For this purpose, primary human myoblasts were freshly isolated and expanded. After 2 days of differentiation, 62 ± 2...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607396/cxcl12-and-osteopontin-from-bone-marrow-derived-mesenchymal-stromal-cells-improve-muscle-regeneration
#12
Yasushi Maeda, Yasuhiro Yonemochi, Yuki Nakajyo, Hideaki Hidaka, Tokunori Ikeda, Yukio Ando
Muscle satellite cells are essential for muscle regeneration. However, efficient regeneration does not occur without muscle-resident mesenchymal progenitor cells. We show here that bone marrow-derived mesenchymal stromal cells (Bm-MSCs) also facilitate muscle regeneration in Duchenne muscular dystrophy (DMD) model mice. Bm-MSCs transplanted into peritoneal cavities of DMD model mice with severe muscle degeneration strongly suppressed dystrophic pathology and improved death-related symptoms, which resulted in dramatic lifespan extension...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28600779/the-landscape-of-genetic-diseases-in-saudi-arabia-based-on-the-first-1000-diagnostic-panels-and-exomes
#13
Dorota Monies, Mohamed Abouelhoda, Moeenaldeen AlSayed, Zuhair Alhassnan, Maha Alotaibi, Husam Kayyali, Mohammed Al-Owain, Ayaz Shah, Zuhair Rahbeeni, Mohammad A Al-Muhaizea, Hamad I Alzaidan, Edward Cupler, Saeed Bohlega, Eissa Faqeih, Maha Faden, Banan Alyounes, Dyala Jaroudi, Ewa Goljan, Hadeel Elbardisy, Asma Akilan, Renad Albar, Hesham Aldhalaan, Shamshad Gulab, Aziza Chedrawi, Bandar K Al Saud, Wesam Kurdi, Nawal Makhseed, Tahani Alqasim, Heba Y El Khashab, Hamoud Al-Mousa, Amal Alhashem, Imaduddin Kanaan, Talal Algoufi, Khalid Alsaleem, Talal A Basha, Fathiya Al-Murshedi, Sameena Khan, Adila Al-Kindy, Maha Alnemer, Sami Al-Hajjar, Suad Alyamani, Hasan Aldhekri, Ali Al-Mehaidib, Rand Arnaout, Omar Dabbagh, Mohammad Shagrani, Dieter Broering, Maha Tulbah, Amal Alqassmi, Maisoon Almugbel, Mohammed AlQuaiz, Abdulaziz Alsaman, Khalid Al-Thihli, Raashda A Sulaiman, Wajeeh Al-Dekhail, Abeer Alsaegh, Fahad A Bashiri, Alya Qari, Suzan Alhomadi, Hisham Alkuraya, Mohammed Alsebayel, Muddathir H Hamad, Laszlo Szonyi, Faisal Abaalkhail, Sulaiman M Al-Mayouf, Hamad Almojalli, Khalid S Alqadi, Hussien Elsiesy, Taghreed M Shuaib, Mohammed Zain Seidahmed, Ibraheem Abosoudah, Hana Akleh, Abdulaziz AlGhonaium, Turki M Alkharfy, Fuad Al Mutairi, Wafa Eyaid, Abdullah Alshanbary, Farrukh R Sheikh, Fahad I Alsohaibani, Abdullah Alsonbul, Saeed Al Tala, Soher Balkhy, Randa Bassiouni, Ahmed S Alenizi, Maged H Hussein, Saeed Hassan, Mohamed Khalil, Brahim Tabarki, Saad Alshahwan, Amira Oshi, Yasser Sabr, Saad Alsaadoun, Mustafa A Salih, Sarar Mohamed, Habiba Sultana, Abdullah Tamim, Moayad El-Haj, Saif Alshahrani, Dalal K Bubshait, Majid Alfadhel, Tariq Faquih, Mohamed El-Kalioby, Shazia Subhani, Zeeshan Shah, Nabil Moghrabi, Brian F Meyer, Fowzan S Alkuraya
In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016-December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants...
August 2017: Human Genetics
https://www.readbyqxmd.com/read/28597942/copy-number-alterations-determined-by-single-nucleotide-polymorphism-array-testing-in-the-clinical-laboratory-are-indicative-of-gene-fusions-in-pediatric-cancer-patients
#14
Tracy M Busse, Jacquelyn J Roth, Donna Wilmoth, Luanne Wainwright, Laura Tooke, Jaclyn A Biegel
Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)-based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients. Ten percent of the bone marrow or solid tumor specimens had SNP array-associated CNAs suggestive of a gene fusion...
June 9, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28596299/postexercise-essential-amino-acid-supplementation-amplifies-skeletal-muscle-satellite-cell-proliferation-in-older-men-24%C3%A2-hours-postexercise
#15
Paul T Reidy, Christopher S Fry, Jared M Dickinson, Micah J Drummond, Blake B Rasmussen
Aged skeletal muscle has an attenuated and delayed ability to proliferate satellite cells in response to resistance exercise. The mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway is a focal point for cell growth, however, the effect of postexercise mTORC1 activation on human skeletal muscle satellite cell (SC) proliferation is unknown. To test the proliferative capacity of skeletal muscle SC in aging muscle to a potent mTORC1 activator (i.e., EAA; essential amino acids) we recruited older (~72y) men to conduct leg resistance exercise (8setsx10reps) without (-EAA; n = 8) and with (+EAA: n = 11) ingestion of 10 g of EAA 1 h postexercise...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28589555/common-and-distinctive-functions-of-the-hippo-effectors-taz-and-yap-in-skeletal-muscle-stem-cell-function
#16
Congshan Sun, Vanessa De Mello, Abdalla Mohamed, Huascar P Ortuste Quiroga, Amaya Garcia-Munoz, Abdullah Al Bloshi, Annie M Tremblay, Alexander von Kriegsheim, Elaina Collie-Duguid, Neil Vargesson, David Matallanas, Henning Wackerhage, Peter S Zammit
Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analyzed Taz in vivo and ex vivo in comparison with Yap. Small interfering RNA knockdown or retroviral-mediated expression of wild-type human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation...
June 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28576418/a-methyl-balanced-diet-prevents-crf-induced-prenatal-stress-triggered-predisposition-to-binge-eating-like-phenotype
#17
Mariana Schroeder, Mira Jakovcevski, Tamar Polacheck, Maya Lebow, Yonat Drori, Mareen Engel, Shifra Ben-Dor, Alon Chen
Binge eating (BE) is a common aberrant form of eating behavior, characterized by overconsumption of food in a brief period of time. Recurrent episodes of BE constitute the BE disorder, which mostly affects females and is associated with early-life adversities. Here, we show that corticotropin releasing factor (CRF)-induced prenatal stress (PNS) in late gestation predisposes female offspring to BE-like behavior that coincides with hypomethylation of hypothalamic miR-1a and downstream dysregulation of the melanocortin system through Pax7/Pax3...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28574407/muscular-response-to-the-first-three-months-of-deflazacort-treatment-in-boys-with-duchenne-muscular-dystrophy
#18
L Jensen, S J Petersson, N O Illum, H C Laugaard-Jacobsen, T Thelle, L H Jørgensen, H D Schrøder
OBJECTIVE: Duchenne muscular dystrophy (DMD) patients are often treated with glucocorticoids; yet their precise molecular action remains unknown. METHODS: We investigated muscle biopsies from nine boys with DMD (aged: 7,6±2,8 yrs.) collected before and after three months of deflazacort treatment and compared them to eight healthy boys (aged: 5,3±2,4 yrs.). mRNA transcripts involved in activation of satellite cells, myogenesis, regeneration, adipogenesis, muscle growth and tissue inflammation were assessed...
June 1, 2017: Journal of Musculoskeletal & Neuronal Interactions
https://www.readbyqxmd.com/read/28572500/neuromuscular-electrical-stimulation-improves-skeletal-muscle-regeneration-through-satellite-cell-fusion-with-myofibers-in-healthy-elderly-subjects
#19
Ester Sara Di Filippo, Rosa Mancinelli, Mariangela Marrone, Christian Doria, Vittore Verratti, Luana Toniolo, Josè Luiz Dantas, Stefania Fulle, Tiziana Pietrangelo
The aim was to determine whether neuromuscular electrical stimulation (NMES) affects skeletal muscle regeneration through a reduction of oxidative status in satellite cells of healthy elderly subjects. Satellite cells from the Vastus lateralis skeletal muscle of 12 healthy elderly subjects before and after 8 weeks of NMES were allowed to proliferate to provide myogenic populations of adult stem cells (myogenic precursor cells; MPCs). These MPCs were then investigated in terms of their proliferation, their basal cytoplasmic free Ca(2+) concentrations, and their expression of myogenic regulatory factors (PAX3, PAX7, MYF5, MYOD, MYOG) and microRNAs (miR-1, miR-133a/b, miR-206)...
June 1, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28542722/a-homozygous-potentially-pathogenic-variant-in-the-paxbp1-gene-in-a-large-family-with-global-developmental-delay-and-myopathic-hypotonia
#20
Essa Alharby, Alia M Albalawi, Abdul Nasir, Sabri A Alhijji, Amer Mahmood, Khushnooda Ramzan, Firoz Abdusamad, Abdulkarim Aljohani, Osama Abdelsalam, Amr Eldardear, Sulman Basit
PAX binding protein 1 (PAXBP1) is an adaptor protein linking the transcription factor PAX3 and PAX7 to the histone methylation machinery. PAXBP1 is a nuclear protein and its high expression is known in brain cerebellar hemisphere and cerebellum. Moreover, it is also found in abundance in muscle precursor cells that are involved in myogenesis and skeletal muscles formation. Whole genome SNP genotyping and exome sequencing in a family with distinct syndrome of global developmental delay and hypotonia mapped the disease locus to the chromosome 21q22...
May 19, 2017: Clinical Genetics
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