Center for HPV Research at IUPUI

poster abstractHuman Papillomavirus (HPV) infection is highly prevalent among women and men and is associated with a number of diseases including genital warts, cervical cancers, other anogenital cancers in both men and women, and cancers of the head and neck. HPV infections are also associated with millions of dollars in annual health care costs. Two vaccines have been developed to prevent HPV infection. Both are approved for use in females ages 9 through 26, and one vaccine is approved for use in 9 to 26 year old males as well. Both vaccines are efficacious, safe, and cost-effective. Despite the great promise of HPV vaccines, vaccination rates in the U.S. are much lower than desired, with 2011 data indicating that 53% of 13-17 year old females received one or more doses and only 37% completed the 3-dose series. The ongoing medical, psychosocial, and financial costs of HPV infection indicate the need for comprehensive, cross-disciplinary research efforts coordinated with community outreach. We have established the Center for Human Papillomavirus (HPV) Research at IUPUI; which fosters cohesion and collaboration among investigators from multiple disciplines and departments at IUPUI, IU Bloomington, and University of Notre Dame pursuing HPV-related research. This group of accomplished senior faculty and promising junior scholars represents a growing synergy between basic, clinical, and social/behavioral sciences. The Center for HPV Research will provide formal infrastructure and resources for pilot research projects, and a collaborative environment for development of proposals for external funding. By capitalizing on the unique strengths of an internationally recognized faculty and IUPUI’s remarkable culture of collaborative and interdisciplinary research, we will establish a world-class center for HPV research, research training, and research translation. The overall mission of the Center for HPV Research will be to improve understanding of HPV transmission, infection, and prevention of HPV infection and its consequences

Low-Latency Rendering

An Application Programming Interface (API) on a pen enabled device provides applications with a low latency rendering path for quickly updating a display in response to pen input, for example from a capacitive or resistive digitizer. The API allows applications to define a hardware overlay that bypasses standard rendering pipeline steps such as graphics processing unit (GPU) rendering, multi-buffering, and operating system compositing. Combined with input prediction, the API enables applications to provide low or near zero latency for pen input. Accordingly, pen enabled applications can provide a higher quality user experience that more closely matches traditional pen and paper. Since the API can be used without changes to underlying hardware, reduced latency is possible even for commodity off-the-shelf parts, obviating the need for costly specialized hardware such as high refresh rate displays

Arenaviral nucleoproteins and the identification of their cellular interacting partners

Members of the Arenaviridae family are able to cause severe disease in humans. The members of this family which induce haemorrhagic fever (HF) are responsible for over 300,000 reported cases per annum, making arenaviruses the largest cause of HF worldwide. Complications from arenavirus induced disease vary from cerebral and developmental complications in infants and the immunocompromised, to HF with cases ultimately fatal in up to 80% of cases. HF causing arenaviruses can induce high grade fever; diarrhoea; vomiting and general malaise, leading to loss of vascular permeability; internal haemorrhaging; disseminated intravascular coagulation and coma. Fundamental mechanisms of the viral replication strategies are currently unknown, it is therefore of paramount importance to increase knowledge in this area in order to identify potential therapeutic strategies. The nucleoprotein (NP) of arenaviruses is essential for viral replication, and is thus a good candidate for further investigation. This study presents the analysis of the host-cell interactome of the HF causing Lujo virus (LUJV) NP, an arenaviral infection associated with 80% mortality. The NP of LUJV was found to associate with members of the translation initiation and elongation complexes by immunoprecipitation and immunofluorescence microscopy. In addition, the NP of the congenital pathogen lymphocytic choriomeningitis virus was found to co-localise with translation associated proteins, with such proteins also identified within viral particles. Finally, it is demonstrated here that the translation of arenaviral-like mRNAs is enhanced in the presence of NP, through a mechanism predicted to be driven by the association of NP with the translation initiation complex eIF4F and the circularisation of mRNAs

Overwintering in New Zealand stick insects

Stick insects are found in a variety of habitats throughout New Zealand, including at least four species that occur at high altitudes. Here they face physiological challenges that differ from their typically warmer lowland habitats, but their strategies to deal with harsh winter conditions are not known. Autumn and winter field surveys, coupled with caging experiments, were conducted to determine which life stages are overwintering in montane and lowland habitats. Data loggers were placed for approximately one year at each site to measure the leaf litter and canopy microhabitat temperatures. From this, we have found that alpine and lowland stick insects persist in a variety of life stages throughout the year despite multiple exposure to freezing temperatures

Tribology: The Story of Lubrication and Wear

Topics addressed include: lubrication and design of high speed rolling element bearings, high speed gears, and traction drives

Positive selection in glycolysis among Australasian stick insects

Background: The glycolytic pathway is central to cellular energy production. Selection on individual enzymes within glycolysis, particularly phosphoglucose isomerase (Pgi), has been associated with metabolic performance in numerous organisms. Nonetheless, how whole energy-producing pathways evolve to allow organisms to thrive in different environments and adopt new lifestyles remains little explored. The Lanceocercata radiation of Australasian stick insects includes transitions from tropical to temperate climates, lowland to alpine habitats, and winged to wingless forms. This permits a broad investigation to determine which steps within glycolysis and what sites within enzymes are the targets of positive selection. To address these questions we obtained transcript sequences from seven core glycolysis enzymes, including two Pgi paralogues, from 29 Lanceocercata species. Results: Using maximum likelihood methods a signature of positive selection was inferred in two core glycolysis enzymes. Pgi and Glyceraldehyde 3-phosphate dehydrogenase (Gaphd) genes both encode enzymes linking glycolysis to the pentose phosphate pathway. Positive selection among Pgi paralogues and orthologues predominately targets amino acids with residues exposed to the protein’s surface, where changes in physical properties may alter enzyme performance. Conclusion: Our results suggest that, for Lancerocercata stick insects, adaptation to new stressful lifestyles requires a balance between maintaining cellular energy production, efficiently exploiting different energy storage pools and compensating for stress-induced oxidative damag

Divergent transcriptional responses to low temperature among populations of alpine and lowland species of New Zealand stick insects (Micrarchus).

In widespread and genetically structured populations, temperature variation may lead to among-population differentiation of thermal biology. The New Zealand stick insect genus Micrarchus contains four species that inhabit different thermal environments, two of which are geographically widespread. RNA-Seq and quantitative PCR were used to investigate the transcriptional responses to cold shock among lowland and alpine species to identify cold-responsive transcripts that differ between the species and to determine whether there is intraspecific geographical variation in gene expression. We also used mitochondrial DNA, nuclear 28S ribosomal DNA and transcriptome-wide SNPs to determine phylogeographic structure and the potential for differences in genetic backgrounds to contribute to variation in gene expression. RNA-Seq identified 2160 unigenes that were differentially expressed as a result of low-temperature exposure across three populations from two species (M. hystriculeus and M. nov. sp. 2), with a majority (68% ± 20%) being population specific. This extensive geographical variation is consistent across years and is likely a result of background genetic differences among populations caused by genetic drift and possibly local adaptation. Responses to cold shock shared among alpine M. nov. sp. 2 populations included the enrichment of cuticular structure-associated transcripts, suggesting that cuticle modification may have accompanied colonization of low-temperature alpine environments and the development of a more cold-hardy phenotype

Identification of cold-responsive genes in a New Zealand alpine stick insect using RNA-Seq.

The endemic New Zealand alpine stick insect Micrarchus nov. sp. 2 regularly experiences sub-zero temperatures in the wild. 454-based RNA-Seq was used to generate a de novo transcriptome and differentiate between treatments to investigate the genetic basis of cold tolerance. Non cold-treated individuals were compared to those exposed to 0°C for 1 h followed by a 1 h recovery period at 20°C. We aligned 607,410 Roche 454 reads, generating a transcriptome of 5235 contigs. Differential expression analysis ranked candidate cold responsive genes for qPCR validation by P-value. The top nine up-regulated candidates, together with eight a priori targets identified from previous studies, had their relative expression quantified using qPCR. Three candidate cold responsive genes from the RNA-Seq data were verified as significantly up-regulated, annotated as: prolyl 4-hydroxylase subunit alpha-1 (P4HA1), staphylococcal nuclease domain-containing protein 1 (snd1) and cuticular protein analogous to peritrophins 3-D2 (Cpap3-d2). All three are novel candidate genes, illustrating the varied response to low temperature across insects

Structural Activity Relationship Study on Dual PLK1 /BRD4 Inhibitor, BI- 2536

Polo-like kinase 1 (PLK1) and BRD4 are two different therapeutic targets in cancer drug discovery. Recently it has been reported that PLK1 inhibitor, BI-2536, is also a potent inhibitor of BRD4. The simultaneous inhibition of PLK1 and BRD4 by a single drug molecule is interesting because this could lead to the development of effective therapeutic strategy for different types of disease conditions in which PLK1 and BRD4 are implicated. Structural activity relationship studies has been carried out on BI-2536 to generate analogs with enhanced dual inhibitory activity against BRD4 and PLK1 as well as to render the molecule selective to one target over the other. UMB101 and 160 have been found to exhibit enhanced dual inhibitory activity with selectivity fold of less than 30, UMB160 being the most potent dual-kinase bromodomain inhibitor (BRD4 IC50 = 28 nM, PLK1 IC50 = 40 nM). UMB131 was found to be the most selective PLK1 inhibitor over BRD4