154 research outputs found

    Pseudoexon activation increases phenotype severity in a Becker muscular dystrophy patient

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    We report a dystrophinopathy patient with an in-frame deletion of DMD exons 45–47, and therefore a genetic diagnosis of Becker muscular dystrophy, who presented with a more severe than expected phenotype. Analysis of the patient DMD mRNA revealed an 82 bp pseudoexon, derived from intron 44, that disrupts the reading frame and is expected to yield a nonfunctional dystrophin. Since the sequence of the pseudoexon and canonical splice sites does not differ from the reference sequence, we concluded that the genomic rearrangement promoted recognition of the pseudoexon, causing a severe dystrophic phenotype. We characterized the deletion breakpoints and identified motifs that might influence selection of the pseudoexon. We concluded that the donor splice site was strengthened by juxtaposition of intron 47, and loss of intron 44 silencer elements, normally located downstream of the pseudoexon donor splice site, further enhanced pseudoexon selection and inclusion in the DMD transcript in this patient

    Professionalism, Golf Coaching and a Master of Science Degree: A commentary

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    As a point of reference I congratulate Simon Jenkins on tackling the issue of professionalism in coaching. As he points out coaching is not a profession, but this does not mean that coaching would not benefit from going through a professionalization process. As things stand I find that the stimulus article unpacks some critically important issues of professionalism, broadly within the context of golf coaching. However, I am not sure enough is made of understanding what professional (golf) coaching actually is nor how the development of a professional golf coach can be facilitated by a Master of Science Degree (M.Sc.). I will focus my commentary on these two issues

    An ultrafast system for signaling mechanical pain in human skin.

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    The canonical view is that touch is signaled by fast-conducting, thickly myelinated afferents, whereas pain is signaled by slow-conducting, thinly myelinated ("fast" pain) or unmyelinated ("slow" pain) afferents. While other mammals have thickly myelinated afferents signaling pain (ultrafast nociceptors), these have not been demonstrated in humans. Here, we performed single-unit axonal recordings (microneurography) from cutaneous mechanoreceptive afferents in healthy participants. We identified A-fiber high-threshold mechanoreceptors (A-HTMRs) that were insensitive to gentle touch, encoded noxious skin indentations, and displayed conduction velocities similar to A-fiber low-threshold mechanoreceptors. Intraneural electrical stimulation of single ultrafast A-HTMRs evoked painful percepts. Testing in patients with selective deafferentation revealed impaired pain judgments to graded mechanical stimuli only when thickly myelinated fibers were absent. This function was preserved in patients with a loss-of-function mutation in mechanotransduction channel PIEZO2. These findings demonstrate that human mechanical pain does not require PIEZO2 and can be signaled by fast-conducting, thickly myelinated afferents

    Domestic Violence and Health Care: Opening Pandora¿s Box ¿ Challenges and Dilemmas

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    In this article we take a critical stance toward the rational progressive narrative surrounding the integration of domestic violence within health care. Whilst changes in recent UK policy and practice have resulted in several tangible benefits, it is argued that there may be hidden dilemmas and challenges. We suggest that the medical model of care and its discursive practices position women as individually accountable for domestic violence-related symptoms and injuries. This may not only be ineffective in terms of service provision but could also have the potential to reduce the political significance of domestic violence as an issue of concern for all women. Furthermore, it is argued that the use of specific metaphors enables practitioners to distance themselves from interactions that may prove to be less comfortable and provide less than certain outcomes. Our analysis explores the possibilities for change that might currently be available. This would appear to involve a consideration of alternative discourses and the reformulation of power relations and subject positions in health care

    DES15E2mlf: a spectroscopically confirmed superluminous supernova that exploded 3.5 Gyr after the big bang

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    We present the Dark Energy Survey (DES) discovery of DES15E2mlf, the most distant superluminous supernova (SLSN) spectroscopically confirmed to date. The light curves and Gemini spectroscopy of DES15E2mlf indicate that it is a Type I superluminous supernova (SLSN-I) at z = 1.861 (a lookback time of ∼10 Gyr) and peaking at MAB = −22.3 ± 0.1 mag. Given the high redshift, our data probe the rest-frame ultraviolet (1400–3500 Å) properties of the SN, finding velocity of the C III feature changes by ∼5600 km s−1 over 14 d around maximum light. We find the host galaxy of DES15E2mlf has a stellar mass of 3.5+3.6 −2.4 × 109 M, which is more massive than the typical SLSN-I host galaxy

    First cosmology results using SNe Ia from the dark energy survey: analysis, systematic uncertainties, and validation

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    International audienceWe present the analysis underpinning the measurement of cosmological parameters from 207 spectroscopically classified type Ia supernovae (SNe Ia) from the first three years of the Dark Energy Survey Supernova Program (DES-SN), spanning a redshift range of 0.01
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