The Zebrafish Homologue of the Human DYT1 Dystonia Gene Is Widely Expressed in CNS Neurons but Non-Essential for Early Motor System Development

DYT1 dystonia is caused by mutation of the TOR1A gene, resulting in the loss of a single glutamic acid residue near the carboxyl terminal of TorsinA. The neuronal functions perturbed by TorsinA[ΔE] are a major unresolved issue in understanding the pathophysiology of dystonia, presenting a critical roadblock to developing effective treatments. We identified and characterized the zebrafish homologue of TOR1A, as a first step towards elucidating the functions of TorsinA in neurons, in vivo, using the genetically-manipulable zebrafish model. The zebrafish genome was found to contain a single alternatively-spliced tor1 gene, derived from a common ancestral locus shared with the dual TOR1A and TOR1B paralogues found in tertrapods. tor1 was expressed ubiquitously during early embryonic development and in multiple adult tissues, including the CNS. The 2.1 kb tor1 mRNA encodes Torsin1, which is 59% identical and 78% homologous to human TorsinA. Torsin1 was expressed as major 45 kDa and minor 47 kDa glycoproteins, within the cytoplasm of neurons and neuropil throughout the CNS. Similar to previous findings relating to human TorsinA, mutations of the ATP hydrolysis domain of Torsin1 resulted in relocalization of the protein in cultured cells from the endoplasmic reticulum to the nuclear envelope. Zebrafish embryos lacking tor1 during early development did not show impaired viability, overt morphological abnormalities, alterations in motor behavior, or developmental defects in the dopaminergic system. Torsin1 is thus non-essential for early development of the motor system, suggesting that important CNS functions may occur later in development, consistent with the critical time window in late childhood when dystonia symptoms usually emerge in DYT1 patients. The similarities between Torsin1 and human TorsinA in domain organization, expression pattern, and cellular localization suggest that the zebrafish will provide a useful model to understand the neuronal functions of Torsins in vivo

A large data resource of genomic copy number variation across neurodevelopmental disorders

Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in \u3c0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (4.3%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are NRXN1, SEH1L, LDLRAD4, GNAL, GNG13, MKRN1, DCTN2, KNDC1, PCMTD2, KIF5A, SYNM, and long non-coding RNAs: AK127244 and PTCHD1-AS. We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants

Brain mapping in a patient with congenital blindness – A case for multimodal approaches

Recent advances in basic neuroscience research across a wide range of methodologies have contributed significantly to our understanding of human cortical electrophysiology and functional brain imaging. Translation of this research into clinical neurosurgery has opened doors for advanced mapping of functionality that previously was prohibitively difficult, if not impossible. Here we present the case of a unique individual with congenital blindness and medically refractory epilepsy who underwent neurosurgical treatment of her seizures. Pre-operative evaluation presented the challenge of accurately and robustly mapping the cerebral cortex for an individual with a high probability of significant cortical re-organization. Additionally, a blind individual has unique priorities in one's ability to read Braille by touch and sense the environment primarily by sound than the non-vision impaired person. For these reasons we employed additional measures to map sensory, motor, speech, language, and auditory perception by employing a number of cortical electrophysiologic mapping and functional magnetic resonance imaging methods. Our data show promising results in the application of these adjunctive methods in the pre-operative mapping of otherwise difficult to localize, and highly variable, functional cortical areas

Space and transatmospheric propulsion technology

This report focuses primarily on Japan's programs in liquid rocket propulsion and propulsion for spaceplane and related transatmospheric areas. It refers briefly to Japan's solid rocket programs and to new supersonic air-breathing propulsion efforts. The panel observed that the Japanese had a carefully thought-out plan, a broad-based program, and an ambitious but achievable schedule for propulsion activity. Japan's overall propulsion program is behind that of the United States at the time of this study, but the Japanese are gaining rapidly. The Japanese are at the forefront in such key areas as advanced materials, enjoying a high level of project continuity and funding. Japan's space program has been evolutionary in nature, while the U.S. program has emphasized revolutionary advances. Projects have typically been smaller in Japan than in the United States, focusing on incremental advances in technology, with an excellent record of applying proven technology to new projects. This evolutionary approach, coupled with an ability to take technology off the shelf from other countries, has resulted in relatively low development costs, rapid progress, and enhanced reliability. Clearly Japan is positioned to be a world leader in space and transatmospheric propulsion technology by the year 2000

Two-Dimensional echocardiographic imaging of distal right coronary artery in kawasaki disease

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38184/1/1870120513_ftp.pd

Joint analysis of stressors and ecosystem services to enhance restoration effectiveness

With increasing pressure placed on natural systems by growing human populations, both scientists and resource managers need a better understanding of the relationships between cumulative stress from human activities and valued ecosystem services. Societies often seek to mitigate threats to these services through large-scale, costly restoration projects, such as the over one billion dollar Great Lakes Restoration Initiative currently underway. To help inform these efforts, we merged high-resolution spatial analyses of environmental stressors with mapping of ecosystem services for all five Great Lakes. Cumulative ecosystem stress is highest in near-shore habitats, but also extends offshore in Lakes Erie, Ontario, and Michigan. Variation in cumulative stress is driven largely by spatial concordance among multiple stressors, indicating the importance of considering all stressors when planning restoration activities. In addition, highly stressed areas reflect numerous different combinations of stressors rather than a single suite of problems, suggesting that a detailed understanding of the stressors needing alleviation could improve restoration planning. We also find that many important areas for fisheries and recreation are subject to high stress, indicating that ecosystem degradation could be threatening key services. Current restoration efforts have targeted high-stress sites almost exclusively, but generally without knowledge of the full range of stressors affecting these locations or differences among sites in service provisioning. Our results demonstrate that joint spatial analysis of stressors and ecosystem services can provide a critical foundation for maximizing social and ecological benefits from restoration investments. www.pnas.org/lookup/suppl/doi:10.1073/pnas.1213841110/-/DCSupplementa

A mathematical model of contact tracing during the 2014-2016 west African ebola outbreak

The 2014-2016 West African outbreak of Ebola Virus Disease (EVD) was the largest and most deadly to date. Contact tracing, following up those who may have been infected through contact with an infected individual to prevent secondary spread, plays a vital role in controlling such outbreaks. Our aim in this work was to mechanistically represent the contact tracing process to illustrate potential areas of improvement in managing contact tracing efforts. We also explored the role contact tracing played in eventually ending the outbreak. We present a system of ordinary differential equations to model contact tracing in Sierra Leonne during the outbreak. Using data on cumulative cases and deaths we estimate most of the parameters in our model. We include the novel features of counting the total number of people being traced and tying this directly to the number of tracers doing this work. Our work highlights the importance of incorporatingchanging behavior into one’s model as needed when indicated by the data and reported trends. Our results show that a larger contact tracing program would have reduced the death toll of the outbreak. Counting the total number of people being traced and including changes in behavior in our model led to better understanding of disease management

The Lantern Vol. 5, No. 1, December 1936

• All of Us • Public Dance • In Tibet, of All Places • Thoughts • Subterranean Conflict on the Campus • Out, Out Into Fragrance and Sweetness • My Soul Steals Out to Meet You In the Night • Bored Young Lady • Guay Shin\u27s Prayer • On Playing Ping-Pong • The Love-Life of One Cat and the Death of Another • My Lady • Danger! Germs Working! • The Wolves • Letters from India • With Apologies to Hamlet • The Dreamhttps://digitalcommons.ursinus.edu/lantern/1015/thumbnail.jp