Regulation of Innate Immune Responses by Bovine Herpesvirus 1 and Infected Cell Protein 0 (bICP0)

Bovine herpesvirus 1 (BoHV-1) infected cell protein 0 (bICP0) is an important transcriptional regulatory protein that stimulates productive infection. In transient transfection assays, bICP0 also inhibits interferon dependent transcription. bICP0 can induce degradation of interferon stimulatory factor 3 (IRF3), a cellular transcription factor that is crucial for activating beta interferon (IFN-β) promoter activity. Recent studies also concluded that interactions between bICP0 and IRF7 inhibit trans-activation of IFN-β promoter activity. The C3HC4 zinc RING (really important new gene) finger located near the amino terminus of bICP0 is important for all known functions of bICP0. A recombinant virus that contains a single amino acid change in a well conserved cysteine residue of the C3HC4 zinc RING finger of bICP0 grows poorly in cultured cells, and does not reactivate from latency in cattle confirming that the C3HC4 zinc RING finger is crucial for viral growth and pathogenesis. A bICP0 deletion mutant does not induce plaques in permissive cells, but induces autophagy in a cell type dependent manner. In summary, the ability of bICP0 to stimulate productive infection, and repress IFN dependent transcription plays a crucial role in the BoHV-1 infection cycle

Bovine Herpes Virus 1 (BHV-1) and Herpes Simplex Virus Type 1 (HSV-1) Promote Survival of Latently Infected Sensory Neurons, in Part by Inhibiting Apoptosis

α-Herpesvirinae subfamily members, including herpes simplex virus type 1 (HSV-1) and bovine herpes virus 1 (BHV-1), initiate infection in mucosal surfaces. BHV-1 and HSV-1 enter sensory neurons by cell-cell spread where a burst of viral gene expression occurs. When compared to non-neuronal cells, viral gene expression is quickly extinguished in sensory neurons resulting in neuronal survival and latency. The HSV-1 latency associated transcript (LAT), which is abundantly expressed in latently infected neurons, inhibits apoptosis, viral transcription, and productive infection, and directly or indirectly enhances reactivation from latency in small animal models. Three anti-apoptosis genes can be substituted for LAT, which will restore wild type levels of reactivation from latency to a LAT null mutant virus. Two small non-coding RNAs encoded by LAT possess anti-apoptosis functions in transfected cells. The BHV-1 latency related RNA (LR-RNA), like LAT, is abundantly expressed during latency. The LR-RNA encodes a protein (ORF2) and two microRNAs that are expressed in certain latently infected neurons. Wild-type expression of LR gene products is required for stress-induced reactivation from latency in cattle. ORF2 has anti-apoptosis functions and interacts with certain cellular transcription factors that stimulate viral transcription and productive infection. ORF2 is predicted to promote survival of infected neurons by inhibiting apoptosis and sequestering cellular transcription factors which stimulate productive infection. In addition, the LR encoded microRNAs inhibit viral transcription and apoptosis. In summary, the ability of BHV-1 and HSV-1 to interfere with apoptosis and productive infection in sensory neurons is crucial for the life-long latency-reactivation cycle in their respective hosts

Latency of Bovine Herpesvirus 1 (BoHV-1) in Sensory Neurons

Bovine herpesvirus 1 (BoHV-1) is an important pathogen of cattle and cofactor for bovine respiratory disease, a polymicrobial disease. Acute infection of cattle leads to abundant expression of lytic cycle viral genes, high levels of virus shedding, and clinical symptoms. Following acute infection, lifelong latency is established in sensory neurons. Only the latency-related (LR) gene locus, which encodes at least two micro-RNAs and several proteins, is abundantly expressed in latently infected neurons. Increased corticosteroids, due to external stressors, disrupt the maintenance of latency and increase the incidence of reactivation from latency, which is crucial for virus transmission. For example, calves latently infected with BoHV-1 consistently reactivate from latency following a single intravenous (IV) injection of the synthetic corticosteroid dexamethasone. In contrast to wild-type BoHV-1, an LR-mutant virus that has three in-frame stop codons at the amino terminus of the first open reading frame in the LR gene (ORF2) does not reactivate from latency following dexamethasone treatment. The ability of dexamethasone to initiate BoHV-1 reactivation from latency in calves makes it an attractive model to identify early events that occur during reactivation from latency. Viral and cellular factors that regulate the BoHV-1 latency-reactivation cycle are discussed in this review

Bovine Herpes Virus 1 (BHV-1) and Herpes Simplex Virus Type 1 (HSV-1) Promote Survival of Latently Infected Sensory Neurons, in Part by Inhibiting Apoptosis

α-Herpesvirinae subfamily members, including herpes simplex virus type 1 (HSV-1) and bovine herpes virus 1 (BHV-1), initiate infection in mucosal surfaces. BHV-1 and HSV-1 enter sensory neurons by cell-cell spread where a burst of viral gene expression occurs. When compared to non-neuronal cells, viral gene expression is quickly extinguished in sensory neurons resulting in neuronal survival and latency. The HSV-1 latency associated transcript (LAT), which is abundantly expressed in latently infected neurons, inhibits apoptosis, viral transcription, and productive infection, and directly or indirectly enhances reactivation from latency in small animal models. Three anti-apoptosis genes can be substituted for LAT, which will restore wild type levels of reactivation from latency to a LAT null mutant virus. Two small non-coding RNAs encoded by LAT possess anti-apoptosis functions in transfected cells. The BHV-1 latency related RNA (LR-RNA), like LAT, is abundantly expressed during latency. The LR-RNA encodes a protein (ORF2) and two microRNAs that are expressed in certain latently infected neurons. Wild-type expression of LR gene products is required for stress-induced reactivation from latency in cattle. ORF2 has anti-apoptosis functions and interacts with certain cellular transcription factors that stimulate viral transcription and productive infection. ORF2 is predicted to promote survival of infected neurons by inhibiting apoptosis and sequestering cellular transcription factors which stimulate productive infection. In addition, the LR encoded microRNAs inhibit viral transcription and apoptosis. In summary, the ability of BHV-1 and HSV-1 to interfere with apoptosis and productive infection in sensory neurons is crucial for the life-long latency-reactivation cycle in their respective hosts

WACCNES CONTAINING BOVINE HERPE SVIRUS 1 ATTENUATED BY MUTATION IN LATENCY-RELATED GENE

Vaccines for pathogenic Strains of bovine herpesvirus 1 (BHV-1) which are based on attenuated BHV-1 having a mutation in the latency-related gene are provided. Live, attenuated vaccines are also provided which express anti gens from other viral or bacterial pathogens and thus form the basis of a variety of vaccines

Arkansas Superintendents\u27 Perceptions of the Quality of Their Preparation Programs

This qualitative research study, using survey research methods, examined the extent to which Arkansas school district superintendents believe that their university-based preparation programs adequately prepared them for the superintendency in Arkansas. An online survey containing a Likert scale was used to determine participants’ perceptions of their programs. The survey instrument also included open-ended questions to enable participants to provide additional feedback related to their superintendent programs. The findings show that 80.7% of participants stated that they would recommend their superintendent preparation programs to aspiring superintendents. The participants did, however, indicate areas where additional focus was needed. Those areas included the Arkansas funding matrix, finance, budgeting, special education, and technology. Areas where participants felt the programs were sufficient were instructional leadership, community relations, board relations, and legal issues

Jones, Clinton

Hq. Co. 1st Bn. 371st Infantry; Fort Huachuca, Arizonahttps://dh.howard.edu/prom_members/1050/thumbnail.jp

Doctor of Philosophy

dissertationThe need for nanoparticle toxicity evaluations is well recognized as the number of applications for nanoparticles continues to grow. This dissertation seeks to reach beyond presently available assessments of nanoparticle-mediated toxicity and mortality to assess the consequences of intravenous nanoparticle injection upon the cellular and molecular participants in the hemostatic response. Based on published reports of severe in vivo coagulopathy, in vitro platelet aggregation and hemolysis for cationic poly(amido amine) (PAMAM) dendrimer nanoparticles, cationic generation-7 PAMAM dendrimers (G7-NH2) were hypothesized to possess strong and specific hemostatic properties and were utilized in the adaptation and development of assays evaluating nanoparticle procoagulant properties. The latter part of this dissertation utilizes the lipopolysaccharide (LPS)-sensitive limulus amoebocyte lysate (LAL) assay a surrogate to explore the hypothesis that intrinsically heightened nanoparticle properties of surface reactivity and specific surface area may disrupt endogenous biochemical cascades. The G7-NH2 were found to affect all key platelet functions, evidenced by severe morphological alteration, extensive aggregation and adhesion, release of alpha granule contents, and attenuation of thrombin generation. It was further demonstrated that extensive, direct, dendrimer-mediated aggregation of fibrinogen occurs via a thrombin-independent, electrostatic mechanism that also included G7-NH2 aggregation of bovine serum albumin and, by extension, the a majority of soluble plasma protein species due to their negative charge domains. Silica nanoparticles and two types of gold nanoparticles were demonstrated to increase the LAL assay response to LPS, while carboxy latex particles attenuated the LAL assay response. This apparent increase in the rate of production for the chromogenic LAL assay product for the gold and silica nanoparticles shows the potential for nanoparticles to exacerbate endogenous inflammatory responses to toxins co-presented in vivo. iv In summary, this dissertation demonstrates the potential for nanoparticle reactivity within or in concert with biological systems and specifically clarifies the mechanism of cationic dendrimer-induced hemostasis. Additionally, this work establishes additional models for the assessment of procoagulant properties of nanoparticles. The specific mechanistic findings presented herein represent an improvement upon the level of analysis usually performed for nanoparticles in the blood system and may guide rational design for safer nanoparticle-based, intravenous therapies

WACCNES CONTAINING BOVINE HERPE SVIRUS 1 ATTENUATED BY MUTATION IN LATENCY-RELATED GENE

Vaccines for pathogenic Strains of bovine herpesvirus 1 (BHV-1) which are based on attenuated BHV-1 having a mutation in the latency-related gene are provided. Live, attenuated vaccines are also provided which express anti gens from other viral or bacterial pathogens and thus form the basis of a variety of vaccines

Principals as Facilitators of Professional Development with Teachers as Adult Learners

The purpose of this study was to investigate the experiences of teachers receiving professional development designed to enhance teacher’s understanding and instructional use of curriculum from principals in an elementary school setting. Further, this mixed methods study examined competencies of principals in creating the conditions for learning in professional development designed to enhance teachers understanding and instructional use of curriculum by answering the following questions: How do Elementary school principals understand and apply the principles of adult learning in professional development designed to enhance elementary teachers’ understanding and instructional use of curriculum? What is the experience of elementary teachers receiving professional development, designed to enhance teachers’ understanding and instructional use of curriculum, from principals in an elementary school setting? What is the experience of the elementary teachers’ change after receiving professional development, designed to enhance teachers’ understanding and instructional use of curriculum, from principals in an elementary school setting? The participants for this study consisted of two primary groups, (1) elementary public school teachers and (2) elementary public school principals. To satisfy the quantitative portion of this study, participants completed a demographic questionnaire and the Modified Instructional Perspectives Inventory (MIPI). Results were analyzed using descriptive statistics. To satisfy the qualitative portion of this study, a sub-sample inclusive of 8 teachers and 4 principals were identified to participate in one semi-structured interview per participant. In addition, principals completed one observation. Analysis of the quantitative data revealed that principals are perceived as average as it relates to their understanding and application of adult learning principles in professional development designed to enhance teachers’ understanding and use of curriculum. Further a line-by-line analysis of the qualitative data identified five primary themes as they relate to principals as facilitators of curriculum related professional development and adult learning principles. The themes include: (a) principal’s leadership qualities, (b) planning and implementing professional development, (c) climate, (d) instructional activities and strategies, and (e) accountability measures