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  • 1
    Online Resource
    Online Resource
    Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
    American Medical Association (AMA) ; 2023
    In:  JAMA Vol. 329, No. 22 ( 2023-06-13), p. 1934-
    Details
    In: JAMA, American Medical Association (AMA), Vol. 329, No. 22 ( 2023-06-13), p. 1934-
    Abstract: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID . Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure SARS-CoV-2 infection. Main Outcomes and Measures PASC and 44 participant-reported symptoms (with severity thresholds). Results A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%] ) were PASC positive at 6 months. Conclusions and Relevance A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
    Type of Medium: Online Resource
    ISSN: 0098-7484
    URL: Article
    DOI: 10.1001/jama.2023.8823
    RVK:
    XA 10000
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 2
    Online Resource
    Online Resource
    A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3
    Elsevier BV ; 2017
    In:  The American Journal of Human Genetics Vol. 100, No. 1 ( 2017-01), p. 128-137
    Details
    In: The American Journal of Human Genetics, Elsevier BV, Vol. 100, No. 1 ( 2017-01), p. 128-137
    Type of Medium: Online Resource
    ISSN: 0002-9297
    URL: Article
    DOI: 10.1016/j.ajhg.2016.11.018
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 1473813-2
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    A cis-regulatory-directed pipeline for the identification of genes involved in cardiac development and disease
    Springer Science and Business Media LLC ; 2021
    In:  Genome Biology Vol. 22, No. 1 ( 2021-12)
    Details
    In: Genome Biology, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2021-12)
    Abstract: Congenital heart diseases are the major cause of death in newborns, but the genetic etiology of this developmental disorder is not fully known. The conventional approach to identify the disease-causing genes focuses on screening genes that display heart-specific expression during development. However, this approach would have discounted genes that are expressed widely in other tissues but may play critical roles in heart development. Results We report an efficient pipeline of genome-wide gene discovery based on the identification of a cardiac-specific cis -regulatory element signature that points to candidate genes involved in heart development and congenital heart disease. With this pipeline, we retrieve 76% of the known cardiac developmental genes and predict 35 novel genes that previously had no known connectivity to heart development. Functional validation of these novel cardiac genes by RNAi-mediated knockdown of the conserved orthologs in Drosophila cardiac tissue reveals that disrupting the activity of 71% of these genes leads to adult mortality. Among these genes, RpL14 , RpS24 , and Rpn8 are associated with heart phenotypes. Conclusions Our pipeline has enabled the discovery of novel genes with roles in heart development. This workflow, which relies on screening for non-coding cis -regulatory signatures, is amenable for identifying developmental and disease genes for an organ without constraining to genes that are expressed exclusively in the organ of interest.
    Type of Medium: Online Resource
    ISSN: 1474-760X
    URL: Article
    DOI: 10.1186/s13059-021-02539-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2040529-7
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  • 4
    Online Resource
    Online Resource
    Spastin is an essential regulator of male meiosis, acrosome formation, manchette structure and nuclear integrity
    The Company of Biologists ; 2023
    In:  Development Vol. 150, No. 6 ( 2023-03-15)
    Details
    In: Development, The Company of Biologists, Vol. 150, No. 6 ( 2023-03-15)
    Abstract: The development and function of male gametes is dependent on a dynamic microtubule network, yet how this is regulated remains poorly understood. We have recently shown that microtubule severing, via the action of the meiotic AAA ATPase protein clade, plays a crucial role in this process. Here, we sought to elucidate the roles of spastin, an as-yet-unexplored member of this clade in spermatogenesis. Using a SpastKO/KO mouse model, we reveal that spastin loss resulted in a complete loss of functional germ cells. Spastin plays a crucial role in the assembly and function of the male meiotic spindle. Consistent with meiotic failure, round spermatid nuclei were enlarged, indicating aneuploidy, but were still able to enter spermiogenesis. During spermiogenesis, we observed extreme abnormalities in manchette structure, acrosome biogenesis and, commonly, a catastrophic loss of nuclear integrity. This work defines an essential role for spastin in regulating microtubule dynamics during spermatogenesis, and is of potential relevance to individuals carrying spastin variants and to the medically assisted reproductive technology industry.
    Type of Medium: Online Resource
    ISSN: 0950-1991 , 1477-9129
    URL: Article
    DOI: 10.1242/dev.201183
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2023
    detail.hit.zdb_id: 2007916-3
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Capturing embryonic development from metamorphosis: how did the terminal patterning signalling pathway of Drosophila evolve?
    Elsevier BV ; 2014
    In:  Current Opinion in Insect Science Vol. 1 ( 2014-07), p. 45-51
    Details
    In: Current Opinion in Insect Science, Elsevier BV, Vol. 1 ( 2014-07), p. 45-51
    Type of Medium: Online Resource
    ISSN: 2214-5745
    URL: Article
    DOI: 10.1016/j.cois.2014.04.007
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
    detail.hit.zdb_id: 2772833-X
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  • 6
    Online Resource
    Online Resource
    Insulin-Like Signalling Influences the Coordination of Larval Hemocyte Number with Body Size in Drosophila melanogaster
    Oxford University Press (OUP) ; 2020
    In:  G3 Genes|Genomes|Genetics Vol. 10, No. 7 ( 2020-07-01), p. 2213-2220
    Details
    In: G3 Genes|Genomes|Genetics, Oxford University Press (OUP), Vol. 10, No. 7 ( 2020-07-01), p. 2213-2220
    Abstract: Blood cells, known as hemocytes in invertebrates, play important and conserved roles in immunity, wound healing and tissue remodelling. The control of hemocyte number is therefore critical to ensure these functions are not compromised, and studies using Drosophila melanogaster are proving useful for understanding how this occurs. Recently, the embryonic patterning gene, torso-like (tsl), was identified as being required both for normal hemocyte development and for providing immunity against certain pathogens. Here, we report that Tsl is required specifically during the larval phase of hematopoiesis, and that tsl mutant larvae likely have reduced hemocyte numbers due to a reduced larval growth rate and compromised insulin signaling. Consistent with this, we find that impairing insulin-mediated growth, either by nutrient deprivation or genetically, results in fewer hemocytes. This is likely the result of impaired insulin-like signaling in the hemocytes themselves, since modulation of Insulin-like Receptor (InR) activity specifically in hemocytes causes concomitant changes to their population size in developing larvae. Taken together, our work reveals the strong relationship that exists between body size and hemocyte number, and suggests that insulin-like signaling contributes to, but is not solely responsible for, keeping these tightly aligned during larval development.
    Type of Medium: Online Resource
    ISSN: 2160-1836
    URL: Article
    DOI: 10.1534/g3.120.401313
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2629978-1
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  • 7
    Online Resource
    Online Resource
    Torso-Like Is a Component of the Hemolymph and Regulates the Insulin Signaling Pathway in Drosophila
    Oxford University Press (OUP) ; 2018
    In:  Genetics Vol. 208, No. 4 ( 2018-04-01), p. 1523-1533
    Details
    In: Genetics, Oxford University Press (OUP), Vol. 208, No. 4 ( 2018-04-01), p. 1523-1533
    Abstract: In Drosophila, key developmental transitions are governed by the steroid hormone ecdysone. A number of neuropeptide-activated signaling pathways control ecdysone production in response to environmental signals, including the insulin signaling pathway, which regulates ecdysone production in response to nutrition. Here, we find that the Membrane Attack Complex/Perforin-like protein Torso-like, best characterized for its role in activating the Torso receptor tyrosine kinase in early embryo patterning, also regulates the insulin signaling pathway in Drosophila. We previously reported that the small body size and developmental delay phenotypes of torso-like null mutants resemble those observed when insulin signaling is reduced. Here we report that, in addition to growth defects, torso-like mutants also display metabolic and nutritional plasticity phenotypes characteristic of mutants with impaired insulin signaling. We further find that in the absence of torso-like, the expression of insulin-like peptides is increased, as is their accumulation in insulin-producing cells. Finally, we show that Torso-like is a component of the hemolymph and that it is required in the prothoracic gland to control developmental timing and body size. Taken together, our data suggest that the secretion of Torso-like from the prothoracic gland influences the activity of insulin signaling throughout the body in Drosophila.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    URL: Article
    DOI: 10.1534/genetics.117.300601
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 1477228-0
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    In vitro sensitivity of median preoptic neurons to angiotensin II, osmotic pressure, and temperature
    American Physiological Society ; 1993
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 264, No. 6 ( 1993-06-01), p. R1200-R1205
    Details
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 264, No. 6 ( 1993-06-01), p. R1200-R1205
    Abstract: In vivo experiments suggest an interaction of the mechanisms involved in the regulation of body fluid balance and body temperature. Increases in plasma osmolality initiate drinking and increase the thermal set point for sweating. The median preoptic nucleus (MnPO) has anatomical connections with brain areas important in fluid balance and cardiovascular regulation and, with the preoptic-anterior hypothalamus, a thermoregulatory region. The present experiments employed in vitro single-unit recordings to determine the sensitivity of MnPO neurons to angiotensin II (ANG II), changes in osmotic pressure, and changes in temperature. One-fifth (11 of 55) of the MnPO neurons responded with changes in firing rate during the ANG II treatment, one-fourth (19 of 75) responded to changes in perfusate osmolality, and there was a significant effect of osmolality and ANG II on the thermosensitivity of 25% of the neurons tested.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    URL: Article
    DOI: 10.1152/ajpregu.1993.264.6.R1200
    Language: English
    Publisher: American Physiological Society
    Publication Date: 1993
    detail.hit.zdb_id: 1477297-8
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Noggin proteins are multifunctional extracellular regulators of cell signaling
    Oxford University Press (OUP) ; 2022
    In:  Genetics Vol. 221, No. 1 ( 2022-05-05)
    Details
    In: Genetics, Oxford University Press (OUP), Vol. 221, No. 1 ( 2022-05-05)
    Abstract: Noggin is an extracellular cysteine knot protein that plays a crucial role in vertebrate dorsoventral patterning. Noggin binds and inhibits the activity of bone morphogenetic proteins via a conserved N-terminal clip domain. Noncanonical orthologs of Noggin that lack a clip domain (“Noggin-like” proteins) are encoded in many arthropod genomes and are thought to have evolved into receptor tyrosine kinase ligands that promote Torso/receptor tyrosine kinase signaling rather than inhibiting bone morphogenic protein signaling. Here, we examined the molecular function of noggin/noggin-like genes (ApNL1 and ApNL2) from the arthropod pea aphid using the dorso-ventral patterning of Xenopus and the terminal patterning system of Drosophila to identify whether these proteins function as bone morphogenic protein or receptor tyrosine kinase signaling regulators. Our findings reveal that ApNL1 from the pea aphid can regulate both bone morphogenic protein and receptor tyrosine kinase signaling pathways, and unexpectedly, that the clip domain is not essential for its antagonism of bone morphogenic protein signaling. Our findings indicate that ancestral noggin/noggin-like genes were multifunctional regulators of signaling that have specialized to regulate multiple cell signaling pathways during the evolution of animals.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    URL: Article
    DOI: 10.1093/genetics/iyac049
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1477228-0
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    The torso-like gene functions to maintain the structure of the vitelline membrane in Nasonia vitripennis , implying its co-option into Drosophila axis formation
    The Company of Biologists ; 2019
    In:  Biology Open
    Details
    In: Biology Open, The Company of Biologists
    Abstract: Axis specification is a fundamental developmental process. Despite this, the mechanisms by which it is controlled across insect taxa are strikingly different. An excellent example of this is terminal patterning, which in Diptera such as Drosophila melanogaster occurs via the localized activation of the receptor tyrosine kinase Torso. In Hymenoptera however, the same process appears to be achieved via localized mRNA. How these mechanisms evolved and what they evolved from remains largely unexplored. Here, we show that torso-like, known for its role in Drosophila terminal patterning, is instead required for the integrity of the vitelline membrane in the hymenopteran wasp Nasonia vitripennis. We find that other genes known to be involved in Drosophila terminal patterning, such as torso and Ptth, also do not function in Nasonia embryonic development. These findings extended to orthologues of Drosophila vitelline membrane proteins known to play a role in localizing Torso-like in Drosophila; in Nasonia these are instead required for dorso-ventral patterning, gastrulation, and potentially terminal patterning. Our data underscores the importance of the vitelline membrane in insect development, and implies phenotypes caused by knockdown of torso-like must be interpreted in light of its function in the vitelline membrane. In addition, our data implies that the signalling components of the Drosophila terminal patterning systems were co-opted from roles in regulating moulting, and co-option into terminal patterning involved the evolution of a novel interaction with the vitelline membrane protein Torso-like.
    Type of Medium: Online Resource
    ISSN: 2046-6390
    URL: Article
    DOI: 10.1242/bio.046284
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2019
    detail.hit.zdb_id: 2632264-X
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