76 research outputs found
A Study of Video-Mediated Opportunities for Self-Directed Learning in Required Core Curriculum
Improving a required course in our curriculum that has proven to be a challenge for our students was the focus of this study. Surveys of both students and instructors attempted to identify specific problem areas. Using the information from these surveys, the researchers developed a series of videos to explain vital course concepts and deployed these into the course sections. The purpose of the videos is to provide consistency across the multiple modalities in which we offer our courses (including online, classroom and via videoconferencing) and to improve overall student understanding. This project seeks to determine how supplemental content focusing on material identified as “difficult,” by students and instructors, can impact student performance. Challenges include the deployment of the videos across various modalities and obtaining sufficient student feedback
Three lateral osteotomy designs for bilateral sagittal split osteotomy: biomechanical evaluation with three-dimensional finite element analysis
<p>Abstract</p> <p>Background</p> <p>The location of the lateral osteotomy cut during bilateral sagittal split osteotomy (BSSO) varies according to the surgeon's preference, and no consensus has been reached regarding the ideal location from the perspective of biomechanics. The purpose of this study was to evaluate the mechanical behavior of the mandible and screw-miniplate system among three lateral osteotomy designs for BSSO by using three-dimensional (3-D) finite element analysis (FEA).</p> <p>Methods</p> <p>The Trauner-Obwegeser (TO), Obwegeser (Ob), and Obwegeser-Dal Pont (OD) methods were used for BSSO. In all the FEA simulations, the distal segments were advanced by 5 mm. Each model was fixed by using miniplates. These were applied at four different locations, including along Champy's lines, to give 12 different FEA miniplate fixation methods. We examined these models under two different loads.</p> <p>Results</p> <p>The magnitudes of tooth displacement, the maximum bone stress in the vicinity of the screws, and the maximum stress on the screw-miniplate system were less in the OD method than in the Ob and TO methods at all the miniplate locations. In addition, Champy's lines models were less than those at the other miniplate locations.</p> <p>Conclusions</p> <p>The OD method allows greater mechanical stability of the mandible than the other two techniques. Further, miniplates placed along Champy's lines provide greater mechanical advantage than those placed at other locations.</p
Regulation of Toll-like receptor signaling by NDP52-mediated selective autophagy is normally inactivated by A20
Toll-like receptor (TLR) signaling is linked to autophagy that facilitates elimination of intracellular pathogens. However, it is largely unknown whether autophagy controls TLR signaling. Here, we report that poly(I:C) stimulation induces selective autophagic degradation of the TLR adaptor molecule TRIF and the signaling molecule TRAF6, which is revealed by gene silencing of the ubiquitin-editing enzyme A20. This type of autophagy induced formation of autophagosomes and could be suppressed by an autophagy inhibitor and lysosomal inhibitors. However, this autophagy was not associated with canonical autophagic processes, including involvement of Beclin-1 and conversion of LC3-I to LC3-II. Through screening of TRIF-interacting ‘autophagy receptors’ in human cells, we identified that NDP52 mediated the selective autophagic degradation of TRIF and TRAF6 but not TRAF3. NDP52 was polyubiquitinated by TRAF6 and was involved in aggregation of TRAF6, which may result in the selective degradation. Intriguingly, only under the condition of A20 silencing, NDP52 could effectively suppress poly(I:C)-induced proinflammatory gene expression. Thus, this study clarifies a selective autophagic mechanism mediated by NDP52 that works downstream of TRIF–TRAF6. Furthermore, although A20 is known as a signaling fine-tuner to prevent excess TLR signaling, it paradoxically downregulates the fine-tuning effect of NDP52 on TLR signaling
Transcriptional Activation of the Adenoviral Genome Is Mediated by Capsid Protein VI
Gene expression of DNA viruses requires nuclear import of the viral genome. Human
Adenoviruses (Ads), like most DNA viruses, encode factors within early
transcription units promoting their own gene expression and counteracting
cellular antiviral defense mechanisms. The cellular transcriptional repressor
Daxx prevents viral gene expression through the assembly of repressive chromatin
remodeling complexes targeting incoming viral genomes. However, it has remained
unclear how initial transcriptional activation of the adenoviral genome is
achieved. Here we show that Daxx mediated repression of the immediate early Ad
E1A promoter is efficiently counteracted by the capsid protein VI. This requires
a conserved PPxY motif in protein VI. Capsid proteins from other DNA viruses
were also shown to activate the Ad E1A promoter independent of Ad gene
expression and support virus replication. Our results show how Ad entry is
connected to transcriptional activation of their genome in the nucleus. Our data
further suggest a common principle for genome activation of DNA viruses by
counteracting Daxx related repressive mechanisms through virion proteins
EBV Tegument Protein BNRF1 Disrupts DAXX-ATRX to Activate Viral Early Gene Transcription
Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV) typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict viral gene expression. Here, we show that the EBV major tegument protein BNRF1 targets host-cell intrinsic defense proteins and promotes viral early gene activation. Specifically, we demonstrate that BNRF1 interacts with the host nuclear protein Daxx at PML nuclear bodies (PML-NBs) and disrupts the formation of the Daxx-ATRX chromatin remodeling complex. We mapped the Daxx interaction domain on BNRF1, and show that this domain is important for supporting EBV primary infection. Through reverse transcription PCR and infection assays, we show that BNRF1 supports viral gene expression upon early infection, and that this function is dependent on the Daxx-interaction domain. Lastly, we show that knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines (LCLs), suggesting that Daxx and ATRX play a role in the regulation of viral chromatin. Taken together, our data demonstrate an important role of BNRF1 in supporting EBV early infection by interacting with Daxx and ATRX; and suggest that tegument disruption of PML-NB-associated antiviral resistances is a universal requirement for herpesvirus infection in the nucleus
Human Cytomegalovirus IE1 Protein Elicits a Type II Interferon-Like Host Cell Response That Depends on Activated STAT1 but Not Interferon-γ
Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary
infection, establishes life-long persistence in all infected individuals. Acute
hCMV infections cause a variety of diseases in humans with developmental or
acquired immune deficits. In addition, persistent hCMV infection may contribute
to various chronic disease conditions even in immunologically normal people. The
pathogenesis of hCMV disease has been frequently linked to inflammatory host
immune responses triggered by virus-infected cells. Moreover, hCMV infection
activates numerous host genes many of which encode pro-inflammatory proteins.
However, little is known about the relative contributions of individual viral
gene products to these changes in cellular transcription. We systematically
analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major
transcriptional activator and antagonist of type I interferon (IFN) signaling,
on the human transcriptome. Following expression under conditions closely
mimicking the situation during productive infection, IE1 elicits a global type
II IFN-like host cell response. This response is dominated by the selective
up-regulation of immune stimulatory genes normally controlled by IFN-γ and
includes the synthesis and secretion of pro-inflammatory chemokines.
IE1-mediated induction of IFN-stimulated genes strictly depends on
tyrosine-phosphorylated signal transducer and activator of transcription 1
(STAT1) and correlates with the nuclear accumulation and sequence-specific
binding of STAT1 to IFN-γ-responsive promoters. However, neither synthesis
nor secretion of IFN-γ or other IFNs seems to be required for the
IE1-dependent effects on cellular gene expression. Our results demonstrate that
a single hCMV protein can trigger a pro-inflammatory host transcriptional
response via an unexpected STAT1-dependent but IFN-independent mechanism and
identify IE1 as a candidate determinant of hCMV pathogenicity
Standard of disocclusion in complete dentures supported by implants without free distal ends: analysis by the finite elements method
Strength increase during ceramic biomaterial-induced bone regeneration: a micromechanical study
A Study of Video-Mediated Opportunities for Self-Directed Learning in Required Core Curriculum
Improving a required course in our curriculum that has proven to be a challenge for our students was the focus of this study. Surveys of both students and instructors attempted to identify specific problem areas. Using the information from these surveys, the researchers developed a series of videos to explain vital course concepts and deployed these into the course sections. The purpose of the videos is to provide consistency across the multiple modalities in which we offer our courses (including online, classroom and via videoconferencing) and to improve overall student understanding. This project seeks to determine how supplemental content focusing on material identified as “difficult,” by students and instructors, can impact student performance. Challenges include the deployment of the videos across various modalities and obtaining sufficient student feedback
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