296 research outputs found
Undergraduates\u27 Perceptions of Campus Response to Sexual Assault: A Butler University Case Study
Sexual assault and misconduct on college campuses is a pervasive and long-standing problem. As such, studentsâ views of campus climate, safety, and their universitiesâ response and prevention policies and practices remain paramount. Using an anonymous survey, the current research examines how undergraduate students at Butler University perceive the campus climate regarding sexual assault and misconduct and how they interpret and assess the universityâs response. The questionnaire posed a series of questions concerning studentsâ knowledge and access to resources, general feelings of safety, and interpretation of university responses. Findings suggest that most respondents believe their university handles sexual assault and misconduct moderately well, but most respondents do not feel comfortable navigating campus resources. Qualitative findings reveal an underlying belief that survivors are not always adequately supported at the university and that students do not trust university resources to meet the needs of someone who has experienced sexual assault or misconduct. Institutional policies and practices are discussed as a way to affect meaningful change on this college campus
Subcellular Localization of Human T-cell Leukemia Virus Type 1 Tax Oncoprotein
Human T-cell Leukemia Virus Type 1 (HTLV-1) is a transforming retrovirus that gives rise to Adult T-cell Leukemia (ATL) and a variety of other subneoplastic conditions such as HTLV-Associated Myelopathy/Tropical Spastic Paraperesis (HAM/TSP). In ATL, the transformation and immortalization of T-lymphocytes has been attributed to the expression and activity of a single HTLV-1 viral protein, namely the trans-activating protein Tax. Although the exact mechanism of Tax-mediated transformation is uncertain, current studies support a model in which Tax induces genomic instability in the host cell through interference with DNA repair mechanisms, dysregulation of cell cycle progression, transcriptional activation of cellular genes, and protein-protein interactions with cellular partners leading to perturbation of their functions. Tax has both nuclear and cytoplasmic activities and shuttles between the two compartments via defined nuclear localization and nuclear export signals (NLS and NES, respectively), but the mechanisms regulating nucleocytoplasmic shuttling and targeting of Tax to distinct subcellular regions have yet to be determined. In this study we identified regions in Tax that regulate nucleocytoplasmic shuttling and dictate subnuclear targeting.
We identified the region in Tax containing the sequence that targets the protein into discrete nuclear foci named Tax Speckled Structures (TSS). These TSS are protein complexes that partially overlap with the cellular marker of splicing SC35 and contain other cellular proteins such as DNA-PKcs and Chia. Targeting Tax to TSS places Tax in a centralized location to affect transcription, DNA damage recognition and other processes, and targeting to these foci is therefore crucial to Tax-mediated transformation. We identified the Tax speckle targeting signal (TSTS) as the Tax region containing amino acids 50-75. This sequence lies downstream from the Tax NLS and is completely separable from the NLS. We demonstrated that a mutant missing the NLS and a mutant missing the TSTS can interact with each other and rescue proper localization through complementation of the deleted domains.
We also determined that dimerization of Tax is required for nuclear localization. The previously defined Tax dimerization domain spans 150 amino acids which represent nearly one-half of the protein. Within this larger domain are three subdomains that were identified as regions required for Tax dimerization. We created Tax mutants deleted in individual dimerization subdomains and assayed their ability to dimerize and their subsequent subcellular localization. Tax mutants deleted in one of the three dimerization subdomains were unable to efficiently homodimerize and were retained in the cytoplasm. They were able to weakly dimerize with wildtype Tax which resulted in partial rescue of nuclear localization. A mutant deleted in two dimerization subdomains was unable to dimerize with itself or with wildtype Tax and remained in the cytoplasm. A Tax mutant that was induced to become a dimer was subsequently able to translocate into the nucleus.
Our studies further identified that cellular proteins including the ubiquitin ligase RNF4 affect the subcellular localization of Tax. Previous studies suggested that ubiquitylation of Tax is associated with its cytoplasmic localization, but the specific ubiquitin ligase involved had not been identified. We demonstrated that RNF4 was able to ubiquitylate Tax in vitro. This study is the first to identify a substrate protein for the ubiquitylation activity of RNF4. Overexpression of RNF4 led to an egress of Tax from the TSS and the nucleus. We co-purified Tax and RNF4 from transfected cell lystates and demonstrated that they are both present in a protein complex. Increasing RNF4 expression increased the cytoplasmic activity of Tax and decreased the nuclear activity of Tax in a dose-dependent manner, suggesting that RNF4\u27s ubiquitylation of Tax affects its subcellular localization and subsequently affects Tax function.
Overall, in this study we have identified novel domains and interactions that contribute to the regulation of the subcellular localization of Tax. The knowledge gained through this work will provide a better understanding of Tax function and its role in cellular transformation
The Sumo-targeted ubiquitin ligase RNF4 regulates the localization and function of the HTLV-1 oncoprotein Tax
The Really Interesting New Gene (RING) Finger Protein 4 (RNF4) represents a class of ubiquitin ligases that target Small Ubiquitin-like Modifier (SUMO)âmodified proteins for ubiquitin modification. To date, the regulatory function of RNF4 appears to be ubiquitin-mediated degradation of sumoylated cellular proteins. In the present study, we show that the Human T-cell Leukemia Virus Type 1 (HTLV-1) oncoprotein Tax is a substrate for RNF4 both in vivo and in vitro. We mapped the RNF4-binding site to a region adjacent to the Tax ubiquitin/SUMO modification sites K280/K284. Interestingly, RNF4 modification of Tax protein results in relocalization of the oncoprotein from the nucleus to the cytoplasm. Overexpression of RNF4, but not the RNF4 RING mutant, resulted in cytoplasmic enrichment of Tax. The RNF4-induced nucleus-to-cytoplasm relocalization was associated with increased NF-ÎșBâmediated and decreased cAMP Response Element-Binding (CREB)âmediated Tax activity. Finally, depletion of RNF4 by RNAi prevented the DNA damageâinduced nuclear/cytoplasmic translocation of Tax. These results provide important new insight into STUbL-mediated pathways that regulate the subcellular localization and functional dynamics of viral oncogenes
Bunker-Type Turkey Feeder
The Oklahoma Agricultural Experiment Station periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311
Hemostatic efficacy of an advanced bipolar sealer in open gynecologic, thoracic, and colectomy procedures: A prospective cohort study
Background
An advanced bipolar (ABP) tissue sealer designed for division of major vessels in open procedures was evaluated in a prospective post-market study. The objective was to provide clinical data for assessment of vessel transection, hemostatic performance and ease of use of the ABP device during open colectomy, gynecologic, and thoracic operations.
Materials and methods
The ABP test device was used in colectomy (n = 36), gynecologic (n = 44), and thoracic (n = 21) procedure groups. Vessels transected with the ABP device were graded intraoperatively on a hemostasis scale of 1â4, defined as follows: Grade1, no bleeding; Grade 2, minor bleeding with no intervention; Grade 3, minor bleeding requiring touchup with the test device or monopolar cautery; and Grade 4, significant bleeding requiring intervention with any additional hemostatic product. The primary performance measure was the percentage of vessels that achieved hemostasis grades â€3. The primary safety endpoint was the summarization of all ABP device-related adverse events (AEs).
Results
For all three procedure groups together, 302 (96.2%) of 314 total vessel transections were scored as hemostasis grades †3, including 270 (86.0%) that were rated Grade 1. Twelve transections (3.8%) were Grade 4, which included 9 vessels transected in the gynecologic group and 3 in the thoracic group. Three subjects experienced a total of 4 device-related AEs, consisting of hematoma, hypotension, procedural pain, and superficial thermal burn. All 4 device-related AEs were mild in severity.
Conclusion
The advanced bipolar device exhibited effective hemostasis, an acceptable safety profile, and ease of use during colectomy, thoracic, and gynecologic procedures
Modelling Hot Spots of Soil Loss by Wind Erosion (SoLoWind) in Western Saxony, Germany
Land Degradation and Development published by John Wiley & Sons, Ltd. While it needs yet to be assessed whether or not wind erosion in Western Saxony is a major point of concern regarding land degradation and fertility, it has already been recognized that considerable off-site effects of wind erosion in the adjacent regions of Saxony-Anhalt and Brandenburg are connected to the spread of herbicides, pesticides and dust. So far, no wind erosion assessment for Western Saxony, Germany, exists. The wind erosion model previously applied for Germany (DIN standard 19706) is considering neither changes in wind direction over time nor influences of field size. This study aims to provide a first assessment of wind erosion for Western Saxony by extending the existing DIN model to a multidirectional model on soil loss by wind (SoLoWind) with new controlling factors (changing wind directions, soil cover, mean field length and mean protection zone) combined by fuzzy logic. SoLoWind is used for a local off-site effect evaluation in combination with high-resolution wind speed and wind direction data at a section of the highway A72. The model attributes 3·6% of the arable fields in Western Saxony to the very-high-wind erosion risk class. A relationship between larger fields (greater than 116 ha) and higher proportions (51·7%) of very-high-wind erosion risk can be observed. Sections of the highway A72 might be under high risk according to the modelled off-site effects of wind erosion. The presented applications showed the potential of SoLoWind to support and consult management for protection measures on a regional scale. © 2016 The Authors. Land Degradation and Development published by John Wiley & Sons, Ltd.The authors would like to thank JĂŒrgen Heinrich and Gudrun
Mayer for the technical revision of the model conception
and the German Weather Service, the Saxon State Office for
the Environment, Agriculture and Geology, the Saxon State
Office for Road Construction and Traffic, the Saxon State
Ministry of the Environment and Agriculture, the Saxon
State Spatial Data and Land Survey Corporation, the Saxon
Road Maintenance Depots, OpenStreetMap and the National
Aeronautics and Space Administration for providing the
datasets. We would also like to thank three anonymous
reviewers for helpful comments.info:eu-repo/semantics/publishedVersio
Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program
The Tax oncoprotein encoded by the Human T-cell leukemia virus type 1 (HTLV-1)
plays a pivotal role in viral persistence and pathogenesis. HTLV-1 infected cells proliferate
faster than normal lymphocytes, expand through mitotic division and accumulate genomic
lesions. Here, we show that Tax associates with the minichromosome maintenance MCM2-7
helicase complex and localizes to origins of replication. Tax modulates the spatiotemporal
program of origin activation and fires supplementary origins at the onset of S phase. Thereby,
Tax increases the DNA replication rate, accelerates S phase progression but also generates a
replicative stress characterized by the presence of genomic lesions. Mechanistically, Tax
favors p300 recruitment and histone hyperacetylation at late replication domains advancing
their replication timing in early S phase
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