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Institution

University of Texas Medical Branch

EducationGalveston, Texas, United States
About: University of Texas Medical Branch is a education organization based out in Galveston, Texas, United States. It is known for research contribution in the topics: Population & Virus. The organization has 22033 authors who have published 38268 publications receiving 1517502 citations. The organization is also known as: The University of Texas Medical Branch at Galveston & UTMB.


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Journal ArticleDOI
TL;DR: Findings indicate that the primate midbrain is the origin of an extensive system of descending spinal pathways, some of which are likely to be involved in mediating descending influences involved in complex motor and sensory behavior.
Abstract: Neurons descending from the midbrain to the spinal cord in the monkey were identified with the retrograde horseradish peroxidase technique. Beginning in the caudal midbrain and extending anteriorly beneath the superior colliculus, large numbers of neurons of the nucleus cuneiformis and lateral central gray were found to project ipsilaterally to the spinal cord. In the posterolateral superior colliculus, neurons of the intermediate and deep layers, stratum griseum intermediale and stratum griseum profundum, were found to give rise to contralateral projections to the upper cervical spinal segments. An ipsilateral tectospinal projection from the anteromedial part of the collicus may also exist. In the red nucleus, neurons of the magnocellular division were shown to give rise to a somatotopically organized projection to the upper cervical cord and spinal enlargements. No neurons of the parvocellular red nucleus were labeled from the spinal cord. In the anterior midbrain, neurons of the interstitial nucleus of Cajal, nucleus of Darkschewitsch, and the adjacent dorsomedial and ventromedial midbrain tegmentum were found to give rise to an extensive ipsilateral descending spinal projection. Neurons located in various midline nuclei including the supratrochlear nucleus, oculomotor nucleus, Edinger-Westphal nucleus, and the ventral part of the central gray were also labeled from the spinal cord. These findings indicate that the primate midbrain is the origin of an extensive system of descending spinal pathways, some of which are likely to be involved in mediating descending influences involved in complex motor and sensory behavior.

236 citations

Journal ArticleDOI
TL;DR: The traditional view on the evolutionary history, host range, and genomic structures of a major group of RNA viruses is revised, suggesting that arthropods may be the ultimate reservoir of the Flaviviridae and related viruses, harboring considerable genetic and phenotypic diversity.
Abstract: Viruses of the family Flaviviridae are important pathogens of humans and other animals, and currently classified into four genera. To better understand their diversity, evolutionary history and genomic flexibility, we used RNA-seq to search for the viruses related to the Flaviviridae in a range of potential invertebrate and vertebrate hosts. Accordingly, we recovered the full genomes of 5 segmented Jingmenviruses and 12 distant relatives of the known Flaviviridae (‘flavi-like9 viruses) from a range of arthropod species. Although these viruses are highly divergent, they share a similar genomic plan and common ancestry with the Flaviviridae in the NS3 and NS5 regions. Remarkably, while these viruses fill in major gaps in the phylogenetic diversity of the Flaviviridae , genomic comparisons reveal important changes in genome structure, genome size, and replication/gene regulation strategy during evolutionary history. In addition, the wide diversity of flavi-like viruses found in invertebrates, as well as their deep phylogenetic positions, suggests that they may represent the ancestral forms from which the vertebrate-infecting viruses evolved. For the vertebrate viruses, we expanded the previously mammal-only pegivirus-hepacivirus group to include a virus from the graceful catshark ( Proscyllium habereri ), which in turn implies that these viruses possess a larger host range than is currently known. In sum, our data show that the Flaviviridae infect a far wider range of hosts and exhibit greater diversity in genome structure than previously anticipated. IMPORTANCE The family Flaviviridae of RNA viruses contains several notorious human pathogens, including dengue virus, West Nile virus, and hepatitis C virus. To date, however, our understanding of the biodiversity and evolution of the Flaviviridae has largely been directed toward vertebrate hosts and their blood-feeding arthropod vectors. Therefore, we investigated an expanded group of potential arthropod and vertebrate host species that have generally been ignored by surveillance programs. Remarkably, these species contained diverse flaviviruses and related viruses that are characterized by major changes in genome size and genome structure, such that these traits are more flexible than previously thought. More generally, these data suggest that arthropods may be the ultimate reservoir of the Flaviviridae and related viruses, harbouring considerable genetic and phenotypic diversity. In sum, this study revises the traditional view on the evolutionary history, host range, and genomic structures of a major group of RNA viruses.

236 citations

Journal ArticleDOI
TL;DR: Radioautographs of early neural tube of chick embryos treated with thymidine-H3 for varying intervals of time give evidence substantiating the concept of inter-kinetic migration of nuclei, as well as confirming DNA synthesis in nuclei of peripheral part of wall.
Abstract: ConclusionRadioautographs of early neural tube of chick embryos treated with thymidine-H3 for varying intervals of time give evidence substantiating the concept of inter-kinetic migration of nuclei. Synthesis of DNA occurs only in nuclei of peripheral part of wall, and does not take place in those of juxta-luminal zone. The period of DNA synthesis continues for at least 4 hours, but does not extend much beyond this time.

235 citations

Journal ArticleDOI
TL;DR: The studies demonstrate the utility of pHAE cultures to model SARS-CoV-2 infection and that both type I and III IFNs can serve as therapeutic options to treat COVID-19 patients.
Abstract: The newly emerged human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a pandemic of respiratory illness. Current evidence suggests that severe cases of SARS-CoV-2 are associated with a dysregulated immune response. However, little is known about how the innate immune system responds to SARS-CoV-2. In this study, we modeled SARS-CoV-2 infection using primary human airway epithelial (pHAE) cultures, which are maintained in an air-liquid interface. We found that SARS-CoV-2 infects and replicates in pHAE cultures and is directionally released on the apical, but not basolateral, surface. Transcriptional profiling studies found that infected pHAE cultures had a molecular signature dominated by proinflammatory cytokines and chemokine induction, including interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and CXCL8, and identified NF-κB and ATF-4 as key drivers of this proinflammatory cytokine response. Surprisingly, we observed a complete lack of a type I or III interferon (IFN) response to SARS-CoV-2 infection. However, pretreatment and posttreatment with type I and III IFNs significantly reduced virus replication in pHAE cultures that correlated with upregulation of antiviral effector genes. Combined, our findings demonstrate that SARS-CoV-2 does not trigger an IFN response but is sensitive to the effects of type I and III IFNs. Our studies demonstrate the utility of pHAE cultures to model SARS-CoV-2 infection and that both type I and III IFNs can serve as therapeutic options to treat COVID-19 patients.IMPORTANCE The current pandemic of respiratory illness, COVID-19, is caused by a recently emerged coronavirus named SARS-CoV-2. This virus infects airway and lung cells causing fever, dry cough, and shortness of breath. Severe cases of COVID-19 can result in lung damage, low blood oxygen levels, and even death. As there are currently no vaccines approved for use in humans, studies of the mechanisms of SARS-CoV-2 infection are urgently needed. Our research identifies an excellent system to model SARS-CoV-2 infection of the human airways that can be used to test various treatments. Analysis of infection in this model system found that human airway epithelial cell cultures induce a strong proinflammatory cytokine response yet block the production of type I and III IFNs to SARS-CoV-2. However, treatment of airway cultures with the immune molecules type I or type III interferon (IFN) was able to inhibit SARS-CoV-2 infection. Thus, our model system identified type I or type III IFN as potential antiviral treatments for COVID-19 patients.

235 citations

Journal Article
TL;DR: Elevated expression of PKC betaII is an important early, promotive event that plays a role in colon cancer development and transgenic mice expressing elevated PKC BetaII in the colonic epithelium exhibit a trend toward increased colon tumor formation after exposure to azoxymethane.
Abstract: Protein kinase C (PKC) has been implicated in colon carcinogenesis in humans and in rodent models. However, little is known about the specific role of individual PKC isozymes in this process. We recently demonstrated that elevated expression of PKC betaII in the colonic epithelium induces hyperproliferation in vivo (N. R. Murray et al., J. Cell Biol., 145: 699-711, 1999). Because hyperproliferation is a major risk factor for colon cancer, we assessed whether specific alterations in PKC betaII expression occur during azoxymethane-induced colon carcinogenesis in mice. An increase in PKC betaII expression was observed in preneoplastic lesions (aberrant crypt foci, 3.7-fold) compared with saline-treated animals, and in colon tumors (7.8-fold; P = 0.011) compared with uninvolved colonic epithelium. In contrast, PKC alpha and PKC betaI (a splicing variant of PKC betaII) expression was slightly decreased in aberrant crypt foci and dramatically reduced in colon tumors. Quantitative reverse transcription-PCR analysis revealed that PKC mRNA levels do not directly correlate with PKC protein levels, indicating that PKC isozyme expression is likely regulated at the posttranscriptional/translational level. Finally, transgenic mice expressing elevated PKC betaII in the colonic epithelium exhibit a trend toward increased colon tumor formation after exposure to azoxymethane. Taken together, our results demonstrate that elevated expression of PKC betaII is an important early, promotive event that plays a role in colon cancer development.

235 citations


Authors

Showing all 22143 results

NameH-indexPapersCitations
Stuart H. Orkin186715112182
Eric R. Kandel184603113560
John C. Morris1831441168413
Joseph Biederman1791012117440
Richard A. Gibbs172889249708
Timothy A. Springer167669122421
Gabriel N. Hortobagyi1661374104845
Roberto Romero1511516108321
Charles B. Nemeroff14997990426
Peter J. Schwartz147647107695
Clifford J. Woolf14150986164
Thomas J. Smith1401775113919
Edward C. Holmes13882485748
Jun Lu135152699767
Henry T. Lynch13392586270
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202330
2022196
20211,617
20201,487
20191,298
20181,152