Telomere Position Effect (TPE) Regulates DUX4 in Human Facioscapulohumeral Muscular Dystrophy (FSHD)

Telomeres may regulate human disease by at least two independent mechanisms. 1) Replicative senescence occurs once short telomeres generate DNA damage signals that produce a barrier to tumor progression. 2) Telomere Position Effect (TPE) can change gene expression at intermediate telomere lengths in cultured human cells. We here report a human disease, facioscapulohumeral muscular dystrophy (FSHD) where telomere length may well contribute to its pathogenesis. FSHD is age-related and genetically only 25-60 kb from the end of chromosome 4q. We used a floxable telomerase to generate isogenic clones with different telomere lengths from patients and their unaffected siblings. DUX4, the primary candidate for FSHD pathogenesis, is upregulated >10-fold in FSHD myoblasts-myotubes with short versus long telomeres, and its expression is inversely proportional to telomere length. FSHD may represent a human disease in which TPE contributes to its age-related phenotype

Magnetized Particle Capture Cross Section for Braneworld Black Hole

Capture cross section of magnetized particle (with nonzero magnetic moment) by braneworld black hole in uniform magnetic field is considered. The magnetic moment of particle was chosen as it was done by \citet{rs99} and for the simplicity particle with zero electric charge is chosen. It is shown that the spin of particle as well as the brane parameter are to sustain the stability of particles circularly orbiting around the black hole in braneworld i.e. spin of particles and brane parameter try to prevent the capture by black hole.Comment: 7 pages, 4 figures, Accepted for publication in Astrophysics & Space Scienc

Analysis of Myogenic and Candidate Disease Biomarkers in FSHD Muscle Cells

The UMMS Wellstone Program is a foundation and NIH-funded cooperative research center focusing on identifying biomarkers for facioscapulohumeral muscular dystrophy (FSHD) to gain insight into the molecular pathology of the disease and to develop potential therapies. FSHD is characterized by progressive wasting of skeletal muscles, with weakness often initiating in facial muscles and muscles supporting the scapula and upper arms. While the genetics associated with FSHD are complex, the major form of the disease, FSHD1, is linked to contraction of the D4Z4 repeat region located at chromosome 4q. Recently, a transcript encoded at the distal end of the repeat region, Dux4-fl, normally expressed in embryonic stem cells and germ cells, was also detected in differentiated muscle cells and biopsies from FSHD subjects, giving rise to the hypothesis that DUX4-FL function contributes to muscle weakness. We established a repository of high quality, well-characterized primary and immortalized muscle cell strains from FSHD and control subjects in affected families to provide biomaterials for cell and molecular studies to the FSHD research community. qPCR and immunostaining analyses demonstrate similar growth and differentiation characteristics in cells from FSHD and control subjects within families. We detected Dux4-fl transcript and protein in FSHD cells as recently described; interestingly, we also detected Dux4-fl in muscle cells from a subset of control individuals, suggesting that any Dux4-fl-mediated myopathy would require additional modifying elements. Microarray analysis of FSHD and control muscle cells demonstrated that several genes were upregulated in FSHD cells, including genes that were concurrently identified as downstream targets of Dux4-fl and as candidate FSHD disease genes. Future studies will further characterize the RNA and protein expression of candidate disease genes in cells from FSHD and control subjects, including nonmanifesting subjects with the D4Z4 lesion but no muscle weakness, and utilizing whole transcriptome sequencing (RNAseq) to identify additional candidates

Isoscalar NN spin-orbit potential from a Skyrme model with scalar mesons

As a first step toward circumventing the difficulty to obtain an attractive isospin-independent NN spin-orbit force from Skyrme-type models involving only pions, we investigate an improved Skyrme Lagrangian that incorporates the scalar-isoscalar meson \epsilon which can be viewed as the cause behind the enhancement of the $\pi \pi S$-wave. We find that at large distances, the main contribution to the spin-orbit potential comes from the scalar Lagrangian and it is found to be attractive. We briefly discuss how to pursue this work to finally obtain a medium-range attractive interaction.Comment: 10 pages (revtex) + 2 figures; use \psfig command. Minor changes in the text and some discussion added in the last section. To be published in Z. Phys.

Surface topography of the InSb-MnSb thin films

In that report we observe a semiconductor eutectic composite InSb-MnSb thin films, prepared by the "flash evaporation" method. The atomic force microscopy and the scanning electron microscopy were employed for investigation microstructure and surface relief of the InSb-MnSb thin films. В этом отчете мы наблюдаем за тонкими пленками полупроводникового электического композита InSb-MnSb, полученными методом «мгновенного испарения». С помощью атомно-силовой микроскопии и сканирующей электронной микроскопии исследованы микроструктура и рельеф поверхности тонких пленок InSb-MnSb

Surface topography of the InSb-MnSb thin films

In that report we observe a semiconductor eutectic composite InSb-MnSb thin films, prepared by the "flash evaporation" method. The atomic force microscopy and the scanning electron microscopy were employed for investigation microstructure and surface relief of the InSb-MnSb thin films. В этом отчете мы наблюдаем за тонкими пленками полупроводникового электического композита InSb-MnSb, полученными методом «мгновенного испарения». С помощью атомно-силовой микроскопии и сканирующей электронной микроскопии исследованы микроструктура и рельеф поверхности тонких пленок InSb-MnSb

X-Linked Genes and Risk of Orofacial Clefts: Evidence from Two Population-Based Studies in Scandinavia

Background: Orofacial clefts are common birth defects of complex etiology, with an excess of males among babies with cleft lip and palate, and an excess of females among those with cleft palate only. Although genes on the X chromosome have been implicated in clefting, there has been no association analysis of X-linked markers. Methodology/Principal Findings: We added new functionalities in the HAPLIN statistical software to enable association analysis of X-linked markers and an exploration of various causal scenarios relevant to orofacial clefts. Genotypes for 48 SNPs in 18 candidate genes on the X chromosome were analyzed in two population-based samples from Scandinavia (562 Norwegian and 235 Danish case-parent triads). For haplotype analysis, we used a sliding-window approach and assessed isolated cleft lip with or without cleft palate (iCL/P) separately from isolated cleft palate only (iCPO). We tested three statistical models in HAPLIN, allowing for: i) the same relative risk in males and females, ii) sex-specific relative risks, and iii) X-inactivation in females. We found weak but consistent associations with the oral-facial-digital syndrome 1 (OFD1) gene (formerly known as CXORF5) in the Danish iCL/P samples across all models, but not in the Norwegian iCL/P samples. In sex-specific analyses, the association with OFD1 was in male cases only. No analyses showed associations with iCPO in either the Norwegian or the Danish sample. Conclusions: The association of OFD1 with iCL/P is plausible given the biological relevance of this gene. However, the lack of replication in the Norwegian samples highlights the need to verify these preliminary findings in other large datasets. More generally, the novel analytic methods presented here are widely applicable to investigations of the role of X-linked genes in complex traits