Enhanced human papillomavirus type 8 oncogene expression levels are crucial for skin tumorigenesis in transgenic mice

AbstractHuman papillomavirus 8 (HPV8) is involved in skin cancer development in epidermodysplasia verruciformis patients. Transgenic mice expressing HPV8 early genes (HPV8-CER) developed papillomas, dysplasias and squamous cell carcinomas. UVA/B-irradiation and mechanical wounding of HPV8-CER mouse skin led to prompt papilloma induction in about 3weeks. The aim of this study was to analyze the kinetics and level of transgene expression in response to skin irritations. Transgene expression was already enhanced 1 to 2days after UVA/B-irradiation or tape-stripping and maintained during papilloma development. The enhanced transgene expression could be assigned to UVB and not to UVA. Papilloma development was thus always paralleled by an increased transgene expression irrespective of the type of skin irritation. A knock-down of E6 mRNA by tattooing HPV8-E6-specific siRNA led to a delay and a lower incidence of papilloma development. This indicates that the early increase of viral oncogene expression is crucial for induction of papillomatosis

Host Species and Captivity Distinguish the Microbiome Compositions of a Diverse Zoo-Resident Non-Human Primate Population

Vast numbers of microorganisms inhabit the mammalian gastrointestinal tract in a complex community referred to as the gut microbiome. An individual’s microbiome may be impacted by genetics, diet, and various environmental factors, and has been associated with many health states and diseases, though specific explanations are lacking. While these communities are well-studied in human populations, non-human primates (NHPs), in particular zoo-resident or captive NHPs, offer distinct advantages to increasing our understanding of factors that influence gut microbiome composition. Here, we characterize the gut microbiome composition of a phylogenetically diverse cohort of NHPs residing in the same urban zoo. We show that despite overlapping and controlled environmental contexts, gut microbiomes are still distinguished between NHP host species. However, when comparing the zoo cohort to wild NHPs, we show that captivity status strongly distinguishes zoo-resident NHPs from their wild counterparts, regardless of host phylogeny. Microbial orders unique to captive NHPs include taxa commonly present in human gut microbiomes. Together, these results demonstrate that differences between NHP species are strongly associated with gut microbiome composition and diversity, suggesting that species-specific approaches should be considered when investigating environmental factors’ influence on gut microbiome composition

Core collapse supernovae in the QCD phase diagram

We compare two classes of hybrid equations of state with a hadron-to-quark matter phase transition in their application to core collapse supernova simulations. The first one uses the quark bag model and describes the transition to three-flavor quark matter at low critical densities. The second one employs a Polyakov-loop extended Nambu-Jona-Lasinio (PNJL) model with parameters describing a phase transition to two-flavor quark matter at higher critical densities. These models possess a distinctly different temperature dependence of their transition densities which turns out to be crucial for the possible appearance of quark matter in supernova cores. During the early post bounce accretion phase quark matter is found only if the phase transition takes place at sufficiently low densities as in the study based on the bag model. The increase critical density with increasing temperature, as obtained for our PNJL parametrization, prevents the formation of quark matter. The further evolution of the core collapse supernova as obtained applying the quark bag model leads to a structural reconfiguration of the central proto-neutron star where, in addition to a massive pure quark matter core, a strong hydrodynamic shock wave forms and a second neutrino burst is released during the shock propagation across the neutrinospheres. We discuss the severe constraints in the freedom of choice of quark matter models and their parametrization due to the recently observed 2 solar mass pulsar and their implications for further studies of core collapse supernovae in the QCD phase diagram.Comment: 19 pages, 4 figures, CPOD2010 conference proceedin

Acquired Epidermodysplasia Verruciformis Due to Multiple and Unusual HPV Infection Among Vertically-Infected, HIV-Positive Adolescents in Zimbabwe

We have characterized the EV-like dermatosis of acquired HIV in 4 adolescents. Multiple HPV types were isolated in skin tissue samples, including β-HPV, but also high levels of HPV 1 and 2. ARV did not improve the EV eruption

Human 13N-ammonia PET studies: the importance of measuring 13N-ammonia metabolites in blood

Dynamic 13N-ammonia PET is used to assess ammonia metabolism in brain, liver and muscle based on kinetic modeling of metabolic pathways, using arterial blood 13N-ammonia as input function. Rosenspire et al. (1990) introduced a solid phase extraction procedure for fractionation of 13N-content in blood into 13N-ammonia, 13N-urea, 13N-glutamine and 13N-glutamate. Due to a radioactive half-life for 13N of 10 min, the procedure is not suitable for blood samples taken beyond 5–7 min after tracer injection. By modifying Rosenspire’s method, we established a method enabling analysis of up to 10 blood samples in the course of 30 min. The modified procedure was validated by HPLC and by 30-min reproducibility studies in humans examined by duplicate 13N-ammonia injections with a 60-min interval. Blood data from a 13N-ammonia brain PET study (from Keiding et al. 2006) showed: (1) time courses of 13N-ammonia fractions could be described adequately by double exponential functions; (2) metabolic conversion of 13N-ammonia to 13N-metabolites were in the order: healthy subjects > cirrhotic patients without HE > cirrhotic patients with HE; (3) kinetics of initial tracer distribution in tissue can be assessed by using total 13N-concentration in blood as input function, whereas assessment of metabolic processes requires 13N-ammonia measurements

Solvation free energy profile of the SCN- ion across the water-1,2-dichloroethane liquid/liquid interface. A computer simulation study

The solvation free energy profile of a single SCN- ion is calculated across the water-1,2-dichloroethane liquid/liquid interface at 298 K by the constraint force method. The obtained results show that the free energy cost of transferring the ion from the aqueous to the organic phase is about 70 kJ/mol, The free energy profile shows a small but clear well at the aqueous side of the interface, in the subsurface region of the water phase, indicating the ability of the SCN- ion to be adsorbed in the close vicinity of the interface. Upon entrance of the SCN- ion to the organic phase a coextraction of the water molecules of its first hydration shell occurs. Accordingly, when it is located at the boundary of the two phases the SCN- ion prefers orientations in which its bulky S atom is located at the aqueous side, and the small N atom, together with its first hydration shell, at the organic side of the interface

The Distribution of Sexually-Transmitted Human Papillomaviruses in HIV Positive and Negative Patients in Zambia, Africa

Background: Human Papillomaviruses (HPV) are double-stranded DNA viruses, considered to be the primary etiological agents in cervical intraepithelial neoplasias and cancers. Approximately 15–20 of the 40 mucosal HPVs confer a high-risk of progression of lesions to invasive cancer. In this study, we investigated the prevalence of sexually transmitted HPVs in Human Immunodeficiency Virus (HIV) positive and negative patients in Zambia, Africa. The rate of high-risk HPV genotypes worldwide varies within each country. Thus, we sought to investigate the rates of HPV infection in sub-Saharan Africa and the potential role of HIV in affecting the HPV genotype distribution. Methods: This retrospective cross-sectional study reports findings on the association and effects of HIV on HPV infections in an existing cohort of patients at University Teaching Hospital (UTH) Lusaka, Zambia. The objective of this study was to assess HPV prevalence, genotype distribution and to identify co-factors that influence HPV infection. Polymerase chain reaction (PCR) with two standard consensus primer sets (CpI/II and GP5+/6+) was used to test for the presence of HPV DNA. Primers specific for β-actin were used to monitor DNA quality. Vaginal lavage samples, collected between 1998-1999 from a total of 70 women, were part of a larger cohort that was also analyzed for HIV and human herpesvirus infection. Seventy of the samples yielded usable DNA. HIV status was determined by two rapid assays, Capillus and Determine. The incidence of HIV and HPV infections and HPV genotype distributions were calculated and statistical significance was determined by Chi-Squared test. Results: We determined that most common HPV genotypes detected among these Zambian patients were types 16 and 18 (21.6% each), which is approximately three-fold greater than the rates for HPV16, and ten-fold greater than the rates for HPV18 in the United States. The worldwide prevalence of HPV16 is approximately 14% and HPV18 is 5%. The overall ratio of high-risk (HR) to low-risk (LR) HPVs in the patient cohort was 69% and 31% respectively; essentially identical to that for the HR and LR distributions worldwide. However, we discovered that HIV positive patients were two-times as likely to have an HR HPV as HIV negative individuals, while the distribution of LR HPVs was unaffected by HIV status. Interestingly, we observed a nine-fold increase in HPV18 infection frequency in HIV positive versus HIV negative individuals. Conclusion: The rate of oncogenic HPVs (type 16 and 18) in Zambia was much higher than in the U.S., potentially providing an explanation for the high-rates of cervical cancer in Zambia. Surprisingly, we discovered a strong association between positive HIV status and the prevalence of HR HPVs, and specifically HPV18