Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Why TV is Not Our Fault: Television Programming, Viewers, and Who\u27s Really in Control

For more than five decades, we\u27ve been told by pundits, commentators, advertisers, scholars, and politicians that television is both a window on the world and a mirror reflecting our culture. We\u27ve been led to believe that it shows us the world\u27s events through news programs and, through entertainment programs, reflects the preferences, values, beliefs, and understandings shared by most Americans. We\u27re told that if you don\u27t like what you see on TV, don\u27t blame the industry, blame yourself. This book dispels the myth that the television industry is just giving viewers the programming they want to see and, thus, we as viewers are \u27responsible\u27 for the existence of shows like Fear Factor and yet another Survivor. In fact, Eileen Meehan explains, viewers exert no demand in the market for ratings, advertising slots, program production, or telecasting. She also counters the idea that TV programs reflect our culture directly. Introducing us to the political economy of television, Meehan covers programming, corporate strategies, advertising, the misnomer of \u27competition\u27 among networks, and organizations that seek more industry accountability. She tells us why TV isn\u27t our fault_and who\u27s really to blame.https://repository.lsu.edu/facultybooks/1600/thumbnail.jp

Napredovanje na levici: zapažanja o kritičnem raziskovanju komuniciranja v ZDA

With the Soviet Union\u27s demise, some academicians argued that Marxist scholarship was similarly irrelevant. Yet, critical voices are still raised in the United States and critical analyses of corporate America remain central in the political economy of mass communication. Within US communication research, \u27political economist\u27 is closely identified with the North American Critical School and thus with Marxist scholarship. While that glosses over the wide variety of positions taken by American practitioners of political economy, it is a fairly reasonable assumption within the field of communications. In the 1950s, a self-consciously critical approach emerged in the work of Dallas Smythe and Herbert I. Schiller. Although ostracized by the field\u27s administrative \u27mainstream\u27, Smythe and Schiller published widely, found an organizational home in the International Association for Media and Communication Research, and inspired a generation of scholars. Their legacy remains vibrant as critical communications research has taken root in the academy, figured in the creation of anti-neo-conservative movements, founded and sustained professional organizations, played a major role in the critique of the mainstream, developed traditions of internal debate and critique, and been targeted for scholarly attack. While much remains to be done, the critical school is clearly moving forward.S koncem Sovjetske zveze so nekateri raziskovalci pokopali tudi marksizem. Vendar se kritični glasovi še slišijo v ZDA in kritične analize korporacijske Amerike ostajajo v središču politične ekonomije množičnega komuniciranja. Politična ekonomija je v ZDA tesno povezana s severnoameriško kritično šolo in marksizmom. V petdesetih letih prejšnjega stoletja sta kritični pristop v svojih delih uveljavila Dallas Smythe in Herbert I. Schiller. Čeprav ju je administrativni glavni tok bojkotiral, sta Smythe in Schiller veliko objavljala, dobila organizacijsko domovanje v Mednarodnem združenju za raziskovanje medijev in komuniciranja in bila vzor za celo generacijo raziskovalcev. Njuna dediščina se ohranja z ukoreninjenjem kritičnega raziskovanja komuniciranja na univerzah, z ustanavljanjem proti-neo-konzervativnih gibanj in profesionalnih organizacijigrala je pomembno vlogo v kritiki "mainstrimovske" tradicije in je sama postala deležna kritike