180 research outputs found

    Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics

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    Derepression of DUX4 in skeletal muscle has emerged as a likely cause of pathology in facioscapulohumeral muscular dystrophy (FSHD). Here we report on the use of antisense phosphorodiamidate morpholino oligonucleotides to suppress DUX4 expression and function in FSHD myotubes and xenografts. The most effective was phosphorodiamidate morpholino oligonucleotide FM10, which targets the polyadenylation signal of DUX4. FM10 had no significant cell toxicity, and RNA-seq analyses of FSHD and control myotubes revealed that FM10 down-regulated many transcriptional targets of DUX4, without overt off-target effects. Electroporation of FM10 into FSHD patient muscle xenografts in mice also down-regulated DUX4 and DUX4 targets. These findings demonstrate the potential of antisense phosphorodiamidate morpholino oligonucleotides as an FSHD therapeutic option

    The shape and erosion of pebbles

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    The shapes of flat pebbles may be characterized in terms of the statistical distribution of curvatures measured along their contours. We illustrate this new method for clay pebbles eroded in a controlled laboratory apparatus, and also for naturally-occurring rip-up clasts formed and eroded in the Mont St.-Michel bay. We find that the curvature distribution allows finer discrimination than traditional measures of aspect ratios. Furthermore, it connects to the microscopic action of erosion processes that are typically faster at protruding regions of high curvature. We discuss in detail how the curvature may be reliable deduced from digital photographs.Comment: 10 pages, 11 figure

    What is in a pebble shape?

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    We propose to characterize the shapes of flat pebbles in terms of the statistical distribution of curvatures measured along the pebble contour. This is demonstrated for the erosion of clay pebbles in a controlled laboratory apparatus. Photographs at various stages of erosion are analyzed, and compared with two models. We find that the curvature distribution complements the usual measurement of aspect ratio, and connects naturally to erosion processes that are typically faster at protruding regions of high curvature.Comment: Phys. Rev. Lett. (to appear

    Ursinus College Alumni Journal, November 1960

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    President\u27s page • Founders\u27 Day • Wayne Brown memorial • Ritter receives degree • Admissions report • Alumnae in Who\u27s Who • Dr. Helfferich honored • Brother of Dalai Lama at Ursinus • Ursinus Women\u27s Club • Old Timers\u27 Day • Psychology\u27s place in a liberal education • The faculty, cornered • Forsan et haec • Education - Scottish and American • 1960 football results • Vernon Morgan, \u2761 Ursinus\u27 greatest runner • Seven years of alumni sponsorship completed: $188,473 collected for Ursinus in this period • Dr. Helfferich speaks • Loyalty Fund all stars • 1960 Loyalty Fund report • Advance Loyalty Fund report for 1961 • Results of the 1960 Loyalty Fund campaign • Contributors for the 1960 Loyalty Fund campaign • New reunion schedule to begin in 1961 • News about ourselves • Weddings • Births • Necrologyhttps://digitalcommons.ursinus.edu/alumnijournal/1069/thumbnail.jp

    Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

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    Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

    US Fish and Wildlife Service 1979 wetland classification: A review

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    In 1979 the US Fish and Wildlife Service published and adopted a classification of wetlands and deepwater habitats of the United States. The system was designed for use in a national inventory of wetlands. It was intended to be ecologically based, to furnish the mapping units needed for the inventory, and to provide national consistency in terminology and definition. We review the performance of the classification after 13 years of use. The definition of wetland is based on national lists of hydric soils and plants that occur in wetlands. Our experience suggests that wetland classifications must facilitate mapping and inventory because these data gathering functions are essential to management and preservation of the wetland resource, but the definitions and taxa must have ecological basis. The most serious problem faced in construction of the classification was lack of data for many of the diverse wetland types. Review of the performance of the classification suggests that, for the most part, it was successful in accomplishing its objectives, but that problem areas should be corrected and modification could strengthen its utility. The classification, at least in concept, could be applied outside the United States. Experience gained in use of the classification can furnish guidance as to pitfalls to be avoided in the wetland classification process

    The Zoning of Semi-Enclosed Bodies of Water According to the Sediment Pollution: The Bay of Algeciras as a Case Example

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    This paper reports a study of the occurrence and levels of polycyclic aromatic hydrocarbons (PAHs) in a bay characterised by a chronic persistent impact. A total of 55 sediment samples were taken at different depths up to 111 m in two sampling campaigns. Chemical analyses were carried out by gas chromatography-mass spectroscopy. The results indicate that: (1) significant spatial variations exist, (2) levels of PAHs are related more strongly to the spatial distribution of sediments than to mineralogy/granulometry, (3) the sediments are slightly-to-moderately contaminated by PAHs, and (4) these PAHs derive from pyrolytic and petrogenic sources. Through use of an innovative data classification system (proposed according to depth and spatial location of sampling points), and using factorial and cluster techniques, five zones have been differentiated depending on the contamination level and source

    The Leucine Zipper Domains of the Transcription Factors GCN4 and c-Jun Have Ribonuclease Activity

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    Basic-region leucine zipper (bZIP) proteins are one of the largest transcription factor families that regulate a wide range of cellular functions. Owing to the stability of their coiled coil structure leucine zipper (LZ) domains of bZIP factors are widely employed as dimerization motifs in protein engineering studies. In the course of one such study, the X-ray structure of the retro-version of the LZ moiety of yeast transcriptional activator GCN4 suggested that this retro-LZ may have ribonuclease activity. Here we show that not only the retro-LZ but also the authentic LZ of GCN4 has weak but distinct ribonuclease activity. The observed cleavage of RNA is unspecific, it is not suppressed by the ribonuclease A inhibitor RNasin and involves the breakage of 3′,5′-phosphodiester bonds with formation of 2′,3′-cyclic phosphates as the final products as demonstrated by HPLC/electrospray ionization mass spectrometry. Several mutants of the GCN4 leucine zipper are catalytically inactive, providing important negative controls and unequivocally associating the enzymatic activity with the peptide under study. The leucine zipper moiety of the human factor c-Jun as well as the entire c-Jun protein are also shown to catalyze degradation of RNA. The presented data, which was obtained in the test-tube experiments, adds GCN4 and c-Jun to the pool of proteins with multiple functions (also known as moonlighting proteins). If expressed in vivo, the endoribonuclease activity of these bZIP-containing factors may represent a direct coupling between transcription activation and controlled RNA turnover. As an additional result of this work, the retro-leucine zipper of GCN4 can be added to the list of functional retro-peptides
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