Translation initiation complex formation in the crenarchaeon Sulfolobus solfataricus

The function of initiation factors in and the sequence of events during translation initiation have been intensively studied in Bacteria and Eukaryotes, whereas in Archaea knowledge on these functions/processes is limited. By employing chemical probing, we show that translation initiation factor aIF1 of the model crenarchaeon Sulfolobus solfataricus binds to the same area on the ribosome as the bacterial and eukaryal orthologs. Fluorescence energy transfer assays (FRET) showed that aIF1, like its eukaryotic and bacterial orthologs, has a fidelity function in translation initiation complex formation, and that both aIF1 and aIF1A exert a synergistic effect in stimulating ribosomal association of the Met-tRNAi^Met binding factor a/eIF2. However, as in Eukaryotes their effect on a/eIF2 binding appears to be indirect. Moreover, FRET was used to analyze for the first time the sequence of events toward translation initiation complex formation in an archaeal model system. These studies suggested that a/eIF2-GTP binds first to the ribosome and then recruits Met-tRNAi^Met, which appears to comply with the operational mode of bacterial IF2, and deviates from the shuttle function of the eukaryotic counterpart eIF2. Thus, despite the resemblance of eIF2 and a/eIF2, recruitment of initiator tRNA to the ribosome is mechanistically different in Pro- and Eukaryotes.     

Further study on Ascogregarina culicis in temperate Argentina: Prevalence and intensity in Aedes aegypti larvae and pupae

The bionomics of South American strains of Ascogregarina spp. are poorly known and the first studies were performed a few years ago. Our main objective was to characterize Ascogregarina culicis population in Aedes aegypti immatures in temperate Argentina. A total of 1800 water-filled containers were inspected within a cemetery of Buenos Aires City through a reproductive period of the host (October 2006-June 2007). The parasite was detected in 16.7% (329/1974) of the immatures and 8.5% (15/177) of the breeding sites. The prevalence decreased from 19.9% in larvae to 6.5% in pupae. In those infected breeding sites, about 85% of the immature mosquitoes harbor the parasite with a median intensity of nine trophozoites per larva and six gametocysts per pupa. The prevalence in shaded containers was higher than in sun exposed ones but the intensity of the infection was quite similar between both lighting conditions. Sun-exposed containers recorded water temperatures significantly higher than those under shade throughout the study period. Parasite trophozoites were only found from January to May with a clear seasonal pattern of prevalence. Monthly values of parasite prevalence and mosquito host (percentage of breeding sites and number of immatures) were significantly correlated at p < 0.05 when a temporal delay of two months was considered. Our results suggest that parasite prevalence is spatially and temporally heterogeneous in temperate urban Argentina, and these variations are associated with the host abundance.     

Surface-bottom relationships in the Gulf of Salerno (Tyrrhenian Sea) over the last 34 kyr: Compositional data analysis of palaeontological proxies and geochemical evidence

The palaeontological, geochemical and mineralogical records of core GNS84-C106 were analysed in order to reconstruct palaeohydrological changes and palaeoproductivity patterns in the Gulf of Salerno for the last 34 kyr. This approach, including compositional analysis of planktonic and benthic assemblages, gave an insight into the relationships between continental, sea surface and bottom environmental changes. The main source of variability of planktonic and benthic assemblages is related respectively to sea surface temperature and palaeobathymetry. Interrelated changes in surface salinity, nutrients, density gradient in the water column and organic fluxes at the bottom act as a secondary factor controlling the composition of both planktonic and benthic assemblages. The highest palaeoproductivity rates were reached during an interval spanning from late glacial to Middle Holocene, in conditions of enhanced continental run-off. During the Early and Middle Holocene, reduced surface salinity and density stratification were also coupled with the development of a deep chlorophyll maximum and enhanced flux or organic matter at the bottom. From about 6.5 kyr B.P. onward, a sharp reduction in palaeoproductivity took place, coupled with an increase in surface salinities.     

CTLA4-Ig interacts with cultured synovial macrophages from rheumatoid arthritis patients and downregulates cytokine production

Introduction  

Co-stimulatory signal B7(CD80/CD86):CD28 is needed in order to activate T cells in immune response. Cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4-Ig) binding to the B7 molecules on antigen-presenting cells downregulates this activation and represents a recent biological treatment in rheumatoid arthritis (RA). Objectives of the study were to investigate the presence of the B7.2 (CD86) molecule and its masking by CTLA4-Ig on cultures of both RA synovial macrophages (RA SM), and of macrophages differentiated from THP-1 cells (M). In addition, the anti-inflammatory effects of CTLA4-Ig on co-cultures of RA SM and M with activated T cells were tested.     

Laparoscopic conservative management of ureteral endometriosis: a survey of eighty patients submitted to ureterolysis

Background  

this study aims to evaluate the effectiveness and safety of laparoscopic conservative management of ureteral endometriosis.     

Human Papillomavirus-16 E7 Interacts with Glutathione S-Transferase P1 and Enhances Its Role in Cell Survival

Background

Human Papillomavirus (HPV)-16 is a paradigm for “high-risk” HPVs, the causative agents of virtually all cervical carcinomas. HPV E6 and E7 viral genes are usually expressed in these tumors, suggesting key roles for their gene products, the E6 and E7 oncoproteins, in inducing malignant transformation.

Methodology/Principal Findings

By protein-protein interaction analysis, using mass spectrometry, we identified glutathione S-transferase P1-1 (GSTP1) as a novel cellular partner of the HPV-16 E7 oncoprotein. Following mapping of the region in the HPV-16 E7 sequence that is involved in the interaction, we generated a three-dimensional molecular model of the complex between HPV-16 E7 and GSTP1, and used this to engineer a mutant molecule of HPV-16 E7 with strongly reduced affinity for GSTP1.When expressed in HaCaT human keratinocytes, HPV-16 E7 modified the equilibrium between the oxidized and reduced forms of GSTP1, thereby inhibiting JNK phosphorylation and its ability to induce apoptosis. Using GSTP1-deficient MCF-7 cancer cells and siRNA interference targeting GSTP1 in HaCaT keratinocytes expressing either wild-type or mutant HPV-16 E7, we uncovered a pivotal role for GSTP1 in the pro-survival program elicited by its binding with HPV-16 E7.

Conclusions/Significance

This study provides further evidence of the transforming abilities of this oncoprotein, setting the groundwork for devising unique molecular tools that can both interfere with the interaction between HPV-16 E7 and GSTP1 and minimize the survival of HPV-16 E7-expressing cancer cells.     

Copy Number Variation of CCL3-like Genes Affects Rate of Progression to Simian-AIDS in Rhesus Macaques (Macaca mulatta)

Variation in genes underlying host immunity can lead to marked differences in susceptibility to HIV infection among humans. Despite heavy reliance on non-human primates as models for HIV/AIDS, little is known about which host factors are shared and which are unique to a given primate lineage. Here, we investigate whether copy number variation (CNV) at CCL3-like genes (CCL3L), a key genetic host factor for HIV/AIDS susceptibility and cell-mediated immune response in humans, is also a determinant of time until onset of simian-AIDS in rhesus macaques. Using a retrospective study of 57 rhesus macaques experimentally infected with SIVmac, we find that CCL3L CNV explains approximately 18% of the variance in time to simian-AIDS (p<0.001) with lower CCL3L copy number associating with more rapid disease course. We also find that CCL3L copy number varies significantly (p<10⁻⁶) among rhesus subpopulations, with Indian-origin macaques having, on average, half as many CCL3L gene copies as Chinese-origin macaques. Lastly, we confirm that CCL3L shows variable copy number in humans and chimpanzees and report on CCL3L CNV within and among three additional primate species. On the basis of our findings we suggest that (1) the difference in population level copy number may explain previously reported observations of longer post-infection survivorship of Chinese-origin rhesus macaques, (2) stratification by CCL3L copy number in rhesus SIV vaccine trials will increase power and reduce noise due to non-vaccine-related differences in survival, and (3) CCL3L CNV is an ancestral component of the primate immune response and, therefore, copy number variation has not been driven by HIV or SIV per se.