74 research outputs found

    Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

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    OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions

    Standardized research protocols enable transdisciplinary research of climate variation impacts in corn production systems

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    The important questions about agriculture, climate, and sustainability have become increasingly complex and require a coordinated, multifaceted approach for developing new knowledge and understanding. A multistate, transdisciplinary project was begun in 2011 to study the potential for both mitigation and adaptation of corn-based cropping systems to climate variations. The team is measuring the baseline as well as change of the system\u27s carbon (C), nitrogen (N), and water footprints, crop productivity, and pest pressure in response to existing and novel production practices. Nine states and 11 institutions are participating in the project, necessitating a well thought out approach to coordinating field data collection procedures at 35 research sites. In addition, the collected data must be brought together in a way that can be stored and used by persons not originally involved in the data collection, necessitating robust procedures for linking metadata with the data and clearly delineated rules for use and publication of data from the overall project. In order to improve the ability to compare data across sites and begin to make inferences about soil and cropping system responses to climate across the region, detailed research protocols were developed to standardize the types of measurements taken and the specific details such as depth, time, method, numbers of samples, and minimum data set required from each site. This process required significant time, debate, and commitment of all the investigators involved with field data collection and was also informed by the data needed to run the simulation models and life cycle analyses. Although individual research teams are collecting additional measurements beyond those stated in the standardized protocols, the written protocols are used by the team for the base measurements to be compared across the region. A centralized database was constructed to meet the needs of current researchers on this project as well as for future use for data synthesis and modeling for agricultural, ecosystem, and climate sciences

    2000 Ohio-Grape Wine Short Course

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    Air, water, sun, and fire--the cooper's footprint on the barrel / Henry Work -- Keeping the bugs unhappy; successful barrel sanitation and maintenance / Henry Work -- Recommended methods for cleaning and maintaining oak cooperage / Phil Burton and Henry Work, with Jim Yerkes -- Chip me, stave me, oak me! The romance, dollars and sense of barrel alternatives / Tim DiPlacido -- Oak experiments / Roland Riesen -- Barrel experiment / Nick Ferrante -- Exploring the versatility and potential of vidal / Roland Riesen -- Ferrante: 1999 vineyard planting / Nick Ferrante -- Breeding rootstocks for current and impending viticultural problems / Andrew Walker -- Grape expectations looking toward traditional and non-traditional sponsors to enhance your event / Doniella Winchell -- Assessing grape maturity by taste and by numbers / Thomas Henick-Kling -- Influence of fruit condition on wine quality / James F. Gallander -- Influence of post bottling storage temperature and SO2 on wine quality / T. E. Steiner -- What we do at harvest to help wine quality / Tony Debevc -- Delivering wine quality / Nick Ferrante -- Criteria for selecting rootstocks / Andrew Walker -- A comparison of Pinot noir production in New York and Burgundy / Pascal Durand and Leslie Weston -- A unique approach to harvest labor / Fran Massaro -- New fungicide registrations for grapes in the year 2000 / Michael Ellis -- Studies to determine time of susceptibility of grape berry and rachis tissues to infection by Phomopsis viticola / O. Erincik, L. V. Madden, D. C. Ferree and M. A. Ellis -- Rootstock performance in Ohio / Arnie Esterer -- Growing your own: vinifera grafting experiments (1999) / Ron Barrett -- Developing an effective fungicide spray program for wine grapes in Ohio / Michael Ellis -- Light and fruit set / David C. Ferree, David M. Scurlock and John C. Schmid -- Soil amendments and mulches in tree health management / Harry Hoitink, Matthew Krause and Randy Zondag -- Report of 5th International Symposium on Cool Climate Viticulture and Enology / Roland Riesen -- Control strategies for soil insects in the vineyard / Roger Williams and Dan Fickl

    Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome

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    Mutations in PNPO are a known cause of neonatal onset seizures that are resistant to pyridoxine but responsive to pyridoxal phosphate (PLP). Mills etal. show that PNPO mutations can also cause neonatal onset seizures that respond to pyridoxine but worsen with PLP, as well as PLP-responsive infantile spasm

    A communal catalogue reveals Earth's multiscale microbial diversity

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    Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe
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