Dendritic cells in dengue virus infection: Targets of virus replication and mediators of immunity

Dendritic cells (DCs) are sentinels of the immune system and detect pathogens at sites of entry, such as the skin. In addition to the ability of DCs to control infections directly via their innate immune functions, DCs help to prime adaptive B and T cell responses via antigen presentation in lymphoid tissues. Infected Aedes aegypti or Ae. albopictus mosquitoes transmit the four dengue virus (DENV) serotypes to humans while probing for small blood vessels in the skin. DENV causes the most prevalent arthropod-borne viral disease in humans, yet no vaccine or specific therapeutic is currently approved. Although primary DENV infection confers life-long protective immunity against re-infection with the same DENV serotype, secondary infection with a different DENV serotype can lead to increased disease severity via cross-reactive T cells or enhancing antibodies. This review summarizes recent findings in humans and animal models about DENV infection of DCs, monocytes and macrophages. We discuss the dual role of DCs as both targets of DENV replication and mediators of innate and adaptive immunity, and summarize immune evasion strategies whereby DENV impairs the function of infected DCs. We suggest that DCs play a key role in priming DENV-specific neutralizing or potentially harmful memory B and T cell responses, and that future DC-directed therapies may help induce protective memory responses and reduce dengue pathogenesis

Branding Access Through the Carolina Covenant: Fostering Institutional Image and Brand

The study demonstrates the ability of financial aid to serve as a key component of institutional image and improve a university’s competitive position while also ensuring the access benefits inherent in supporting low-income students. The implications of this work provide an additional rationale for increasing financial aid budgets and substantiate proof of the market’s ability to improve access

An analysis of hearing aid fittings in adults using cochlear implants and contralateral hearing aids

OBJECTIVES/HYPOTHESIS: The objective of this study was to assess the appropriateness of hearing aid fittings within a sample of adult cochlear implant recipients who use a hearing aid in the contralateral ear (i.e., bimodal stimulation). METHODS: The hearing aid gain was measured using real ear testing for 14 postlingually deaf English-speaking adults who use a cochlear implant in the contralateral ear. Unaided and aided audiometric testing assessed the degree of functional gain derived from hearing aid use. RESULTS: On average, the target to actual output level difference was within 10 dB only at frequencies of 750 Hz and 1,000 Hz. Only 1 of the 14 study participants had a hearing aid for which the majority of the tested frequencies were within 10 dB of the target gain. In addition, a greater amount of functional gain (i.e., the increase in unaided behavioral thresholds after amplification) was provided for lower frequencies than higher frequencies. CONCLUSIONS: Hearing aid settings in our sample were suboptimal and may be regarded as a contributing factor to the variability in bimodal benefit. Refining hearing aid fitting strategies tailored to the needs of the concurrent cochlear implant and hearing aid user is recommended

Mycophenolic Acid Inhibits Dengue Virus Infection by Preventing Replication of Viral RNA

AbstractDengue fever is a mosquito-borne viral disease of global importance with no available antiviral therapy. We assessed the ability of mycophenolic acid (MPA), a drug currently used as an immunosuppressive agent, to inhibit dengue virus (DV) antigen expression, RNA replication, and virus production. Pharmacological concentrations of MPA effectively blocked DV infection, decreasing the percentage of infected cells by 99% and the levels of secreted virus by up to a millionfold. Results were reproduced with four hepatoma cell lines and different flaviviruses, including a recent West Nile virus isolate. Experiments were performed to define the stage in the viral lifecycle at which MPA abrogates infection. Early steps in viral infection, such as viral entry and nucleocapsid uncoating, were not the primary targets of MPA action since its inhibitory effect was retained when naked DV RNA was transfected directly into cells. Biosynthetic labeling experiments showed that MPA did not block the initial phase of viral translation but did interfere with viral protein synthesis in the amplification phase. Quantitative RT-PCR demonstrated that MPA prevented the accumulation of viral positive- and negative-strand RNA as the infection proceeded. We conclude that MPA inhibits flavivirus infection by preventing synthesis and accumulation of viral RNA

A 2dF spectroscopic study of globular clusters in NGC 5128: Probing the formation history of the nearest giant Elliptical

We have performed a spectroscopic study of globular clusters (GCs) in the giant elliptical NGC 5128 using the 2dF facility at the Anglo-Australian telescope. We obtained integrated optical spectra for a total of 254 GCs, 79 of which are newly confirmed on the basis of their radial velocities and spectra. In addition, we obtained an integrated spectrum of the galaxy starlight along the southern major axis. We derive an empirical metallicity distribution function (MDF) for 207 GCs (~14 of the estimated total GC system) based upon Milky Way GCs. This MDF is multimodal at high statistical significance with peaks at [Z/H]~-1.3 and -0.5. A comparison between the GC MDF and that of the stellar halo at 20 kpc (~4 Reff) reveals close coincidence at the metal-rich ends of the distributions. However, an inner 8 kpc stellar MDF shows a clear excess of metal-rich stars when compared to the GCs. We compare a higher S/N subsample (147 GCs) with two stellar population models which include non-solar abundance ratio corrections. The vast majority of our sample (~90%) appears old, with ages similar to the Milky Way GC system. There is evidence for a population of intermediate-age (~4-8 Gy) GCs (<15% of the sample) which are on average more metal-rich than the old GCs. We also identify at least one younger cluster (~1-2 Gy) in the central regions of the galaxy. Our observations are consistent with a picture where NGC 5128 has undergone at least two mergers and/or interactions involving star formation and limited GC formation since z=1, however the effect of non-canonical hot stellar populations on the integrated spectra of GCs remains an outstanding uncertainty in our GC age estimates.Comment: 17 figures, some long table

Goldilocks and Journal Publication: Finding a Fit That\u27s Just Right

Getting your work published in journals in ways that will help to advance your scholarly record is a complex and multifaceted process. This article is written for early career researchers and graduate and postgraduate students, providing practical advice about what to consider when developing a research and publication profile and establishing yourself within a research community. It explains a range of criteria that are useful to consider when choosing the best journal “fit” for each publication and for your academic trajectory. We hope that considering the elements identified and explained in this article will help you to find a fit that is “just right” for each of your future publications

Reconstruction of midface defect from idiopathic destructive process using Medpor implant

Importance Reconstruction of the midface remains a challenging task for even the most experienced surgeon, with a host of reconstructive options including free tissue transfer, allografts, or prosthetic implants. Presented here is a case of idiopathic bony destruction of the right midface in a 19 year old female, creating a unique defect requiring repair. Objective Demonstrate a unique case of severe maxillary degeneration and discuss the associated reconstructive challenges and final repair with a prosthetic implant. Design Case report. Results The patient presented with a 7 month history of an idiopathic progressive deformity of the right cheek. Computed tomography of the paranasal sinuses revealed extensive bone loss of the right midface and orbit. The patient underwent facial reconstruction using a customized Medpor (Stryker Corp, Kalamazoo, MI) implant. At 6 month follow-up the patient and physician were both pleased with the patient's overall appearance. The patient did have some residual lower lid retraction present as well as some lateral pull at the lateral canthus outward from the orbit itself. Conclusions Preoperative planning for midface reconstruction requires a deep understanding of the aesthetic, functional, and supportive roles this structure holds. Computer assistance allows the creation of custom made implants, providing the reconstructive surgeon with innovative options for reconstruction with minimal morbidity to the patient. As the technology around the design and creation of the custom implants continues to improve, the role of computer assistance in reconstruction will become more prominent