A Mathematical Analysis on the Transmission Dynamics of Neisseria gonorrhoeae

In this project, we analyze an epidemiological model describing the transmission of gonorrhea. We address two stratifications: one based on age groups and one based on education levels, each with a core sexual activity class and two noncore sexual activity classes. Using parameters based on sexual behavior in the United States, we address the impact of the average number of partners per year for each sexual activity class on the behavior of the model around two equilibrium points: a disease-free equilibrium and an endemic equilibrium. The focus of the project is to identify the conditions leading to the existence of each of the equilibrium points, analyze the stability of these points, and discuss the results. Ultimately, the goal of the project is to find conditions for the bifurcation of the two equilibrium points, in order to find the conditions resulting in the eradication of gonorrhea

The Potential Roles of Long Noncoding RNAs (lncRNA) in Glioblastoma Development

Long noncoding RNA (lncRNA) may contribute to the initiation and progression of tumor. In this study, we first systematically compared lncRNA and mRNA expression between glioblastoma and paired normal brain tissues using microarray data. We found 27 lncRNA and 82 mRNA significantly upregulated in glioblastoma, as well as 198 lncRNA and 285 mRNA significantly downregulated in glioblastoma. We identified 138 coexpressed lncRNA–mRNA pairs from these differentially expressed lncRNA and genes. Subsequent pathway analysis of the lncRNA-paired genes indicated that EphrinB–EPHB, p75-mediated signaling, TNFα/NF-κB, and ErbB2/ErbB3 signaling pathways might be altered in glioblastoma. Specifically, lncRNA RAMP2-AS1 had significant decrease of expression in glioblastoma tissues and showed coexpressional relationship with NOTCH3, an important tumor promoter in many neoplastic diseases. Our follow up experiment indicated that (i) an overexpression of RAMP2-AS1 reduced glioblastoma cell proliferation in vitro and also reduced glioblastoma xenograft tumors in vivo; (ii) NOTCH3 and RAMP2-AS1 coexpression rescued the inhibitory action of RAMP2-AS1 in glioblastoma cells; and (iii) RNA pull-down assay revealed a direct interaction of RAMP2-AS1 with DHC10, which may consequently inhibit, as we hypothesize, the expression of NOTCH3 and its downstream signaling molecule HES1 in glioblastoma. Taken together, our data revealed that lncRNA expression profile in glioblastoma tissue was significantly altered; and RAMP2-AS1 might play a tumor suppressive role in glioblastoma through an indirect inhibition of NOTCH3. Our results provided some insights into understanding the key roles of lncRNA–mRNA coregulation in human glioblastoma and the mechanisms responsible for glioblastoma progression and pathogenesis. Mol Cancer Ther; 15(12); 2977–86. ©2016 AACR

Late cardiac events after allogeneic stem cell transplant: Incidence, risk factors, and impact on overall survival

BACKGROUND: There is limited data on the impact of cardiac disease on long term outcomes of allogeneic stem cell transplant (alloSCT). Our study aims to describe the incidence of late cardiac events after alloSCT, identify risk factors for developing a late cardiac event, and illustrate the impact of late cardiac events on overall survival. METHODS: Patients who underwent alloSCT from 2007 to 2017 and survived more than 1 year after transplant (N = 804) were included. Gray\u27s sub-distribution methods, while accounting for death as a competing risk, were used to calculate the cumulative incidence of late cardiac events. Univariate regression models based on Gray\u27s sub-distribution were fitted to assess the potential predictive effects of baseline characteristics on the risk of developing any late cardiac events. Univariate Cox proportional hazard regression models were used to evaluate the association between late cardiac events and overall survival. RESULTS: The cumulative incidence of a late cardiac event at 5 years after transplant was 22% (95% CI 19-25%). The most frequent cardiac event was a decline in LVEF to \u3c 45% with a cumulative incidence of 9% (95% CI 7-11%). Patients were at significantly increased hazard of developing a late cardiac event if they had a history of congestive heart failure prior to alloSCT (HR 4.53, 95% CI 2.57-7.97, p-value \u3c 0.001), a decline in LVEF to \u3c 45% (HR 3.95, 95% CI 2.09-7.47, p-value \u3c 0.001) or cerebral vascular accident (HR 3.13, 95% CI 1.38-7.06, p-value 0.004). Transplant characteristics such as primary disease, donor type, use of TBI, myeloablative conditioning regimen or tyrosine kinase inhibitor had no significant association with late cardiac events. Almost all cardiac events demonstrated a significantly increased risk of death. This hazard was the highest in patients who experienced an atrial arrhythmia (HR 10.6, 95% CI 7.7-14.6). CONCLUSION: Adverse cardiac events are relatively common late after alloSCT with identifiable risk factors such as medical comorbidities prior to transplant and are associated with a negative impact on overall survival

A Novel HDL-Mimetic Peptide HM-10/10 Protects RPE and Photoreceptors in Murine Models of Retinal Degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD. Oxidative stress plays a key role in the development of AMD. We generated a chimeric high-density lipoprotein (HDL), mimetic peptide named HM-10/10, with anti-oxidant properties and investigated its potential for the treatment of retinal disease using cell culture and animal models of RPE and photoreceptor (PR) degeneration. Treatment with HM-10/10 peptide prevented human fetal RPE cell death caused by tert-Butyl hydroperoxide (tBH)-induced oxidative stress and sodium iodate (NaIO3), which causes RPE atrophy and is a model of geographic atrophy in mice. We also show that HM-10/10 peptide ameliorated photoreceptor cell death and significantly improved retinal function in a mouse model of N-methyl-N-nitrosourea (MNU)-induced PR degeneration. Our results demonstrate that HM-10/10 protects RPE and retina from oxidant injury and can serve as a potential therapeutic agent for the treatment of retinal degeneration

Modulation of the Nuclear Transcription Factor of Activated T Cells by Duck Hepatitis B Virus

During infection with hepadnaviruses besides the infectious agent a high number of subviral particles without nucleocapsids are produced, which are able to change the infection dramatically. In addition, it was observed that the activation of the nuclear factor of activated T cells, regulated usually in cells of the immune system, was strongly influenced after infection. When primary duck liver cells were infected with purified virions of duck hepatitis B virus the activation of this factor was reduced in a similar way as it was achieved by inhibition of calcineurin, a cellular phosphatase necessary to control the factor, whereas the addition of subviral particles inhibited this reduction. It was found that the large surface protein of the virus was responsible for the reduced activity. Although this protein was embedded in similar amounts into the envelopes of both particles, only virions were able to inhibit the activity of the nuclear factor. An explanation of the different performances of the particles in primary duck liver cells apparently depends on the individual mode of insertion of the large surface proteins into the viral membrane. Furthermore, the nuclear factor of activated T cells could only be detected in liver sinusoidal endothelial cells, which was shown being attracted by virions but not by subviral particles

Lymphoadenopathy during Lyme Borreliosis Is Caused by Spirochete Migration-Induced Specific B Cell Activation

Lymphadenopathy is a hallmark of acute infection with Borrelia burgdorferi, a tick-borne spirochete and causative agent of Lyme borreliosis, but the underlying causes and the functional consequences of this lymph node enlargement have not been revealed. The present study demonstrates that extracellular, live spirochetes accumulate in the cortical areas of lymph nodes following infection of mice with either host-adapted, or tick-borne B. burgdorferi and that they, but not inactivated spirochetes, drive the lymphadenopathy. The ensuing lymph node response is characterized by strong, rapid extrafollicular B cell proliferation and differentiation to plasma cells, as assessed by immunohistochemistry, flow cytometry and ELISPOT analysis, while germinal center reactions were not consistently observed. The extrafollicular nature of this B cell response and its strongly IgM-skewed isotype profile bear the hallmarks of a T-independent response. The induced B cell response does appear, however, to be largely antigen-specific. Use of a cocktail of recombinant, in vivo-expressed B. burgdorferi-antigens revealed the robust induction of borrelia-specific antibody-secreting cells by ELISPOT. Furthermore, nearly a quarter of hybridomas generated from regional lymph nodes during acute infection showed reactivity against a small number of recombinant Borrelia-antigens. Finally, neither the quality nor the magnitude of the B cell responses was altered in mice lacking the Toll-like receptor adaptor molecule MyD88. Together, these findings suggest a novel evasion strategy for B. burgdorferi: subversion of the quality of a strongly induced, potentially protective borrelia-specific antibody response via B. burdorferi's accumulation in lymph nodes