Dosage compensation in Drosophila is mediated by the MSL complex, which increases male X-linked gene expression approximately 2-fold. The MSL complex preferentially binds the bodies of active genes on the male X, depositing H4K16ac with a 3' bias. Two models have been proposed for the influence of the MSL complex on transcription: one based on promoter recruitment of RNA polymerase II (Pol II), and a second featuring enhanced transcriptional elongation. Here, we utilize nascent RNA sequencing to document dosage compensation during transcriptional elongation. We also compare X and autosomes from published data on paused and elongating polymerase in order to assess the role of Pol II recruitment. Our results support a model for differentially regulated elongation, starting with release from 5' pausing and increasing through X-linked gene bodies. Our results highlight facilitated transcriptional elongation as a key mechanism for the coordinated regulation of a diverse set of genes.
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http://dx.doi.org/10.1016/j.celrep.2013.09.037 | DOI Listing |
Cephalalgia
January 2025
Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA.
Background: Women with endometriosis are more likely to have migraine. The mechanisms underlying this co-morbidity are unknown. Prolactin, a neurohormone secreted and released into circulation from the anterior pituitary, can sensitize sensory neurons from female, but not male, rodents, monkeys and human donors.
View Article and Find Full Text PDFJ Neurol
January 2025
Division of Child Neurology, Children's Hospital of Philadelphia, Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Background: The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).
Methods: Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.
Primary Endpoints: pharmacokinetics, pharmacodynamics (CD19 B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.
BMC Public Health
January 2025
Department of Social Work, Hong Kong Baptist University, Hong Kong, China.
Background: The COVID-19 pandemic has had profound psychophysiological and socioeconomic effects worldwide. COVID-19 anxiety syndrome (CAS) is a specific cluster of maladaptive coping strategies, including perseveration and avoidance behaviours, in response to the perceived threat and fear of COVID-19. CAS is distinct from general COVID-19 anxiety.
View Article and Find Full Text PDFNeurology
January 2025
The Dubowitz Neuromuscular Centre, Developmental Neurosciences Department, University College London, Great Ormond Street Institute of Child Health, United Kingdom.
Background And Objectives: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.
View Article and Find Full Text PDFDev Cell
January 2025
King's College London, Centre for Gene Therapy and Regenerative Medicine, School of Basic & Medical Biosciences, Faculty of Life Sciences and Medicine, London, UK; King's College London, Guy's Hospital Assisted Conception Unit, Department of Women and Children's Health, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, London, UK. Electronic address:
Female primordial germ cells (PGCs) undergo X chromosome reactivation (XCR) during genome-wide reprogramming. XCR kinetics and dynamics are poorly understood at a molecular level. Here, we apply single-cell RNA sequencing and chromatin profiling on germ cells from F mouse embryos, performing a precise appraisal of XCR spanning from migratory-stage PGCs to gonadal germ cells.
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