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. © 2009 Mileo et al

The Mitochondrial Genome of Toxocara canis

Toxocara canis (Ascaridida: Nematoda), which parasitizes (at the adult stage) the small intestine of canids, can be transmitted to a range of other mammals, including humans, and can cause the disease toxocariasis. Despite its significance as a pathogen, the genetics, epidemiology and biology of this parasite remain poorly understood. In addition, the zoonotic potential of related species of Toxocara, such as T. cati and T. malaysiensis, is not well known. Mitochondrial DNA is known to provide genetic markers for investigations in these areas, but complete mitochondrial genomic data have been lacking for T. canis and its congeners. In the present study, the mitochondrial genome of T. canis was amplified by long-range polymerase chain reaction (long PCR) and sequenced using a primer-walking strategy. This circular mitochondrial genome was 14162 bp and contained 12 protein-coding, 22 transfer RNA, and 2 ribosomal RNA genes consistent for secernentean nematodes, including Ascaris suum and Anisakis simplex (Ascaridida). The mitochondrial genome of T. canis provides genetic markers for studies into the systematics, population genetics and epidemiology of this zoonotic parasite and its congeners. Such markers can now be used in prospecting for cryptic species and for exploring host specificity and zoonotic potential, thus underpinning the prevention and control of toxocariasis in humans and other hosts

QUANTITATIVE STUDY OF NEURONAL DEGENERATION INDUCED BY RICINUS TOXIN AND CRUSH OF POSTGANGLIONIC NERVES IN THE CILIARY GANGLION OF QUAIL

The effects of Ricinus toxin on the neurons of the ciliary ganglia were investigated in the quail. The neuronal death and the morphological alterations of the ganglionic cells were assessed following injection of the toxin in the anterior chamber of the eye or after application of the toxin on the postganglionic nerves at a crush site. A 45% loss of choroid neurons without loss of ciliary neurons was observed after postganglionic nerve crush alone. Injection of the toxin in the anterior chamber of the eye led to a selective loss of ciliary neurons (38%). Application of the toxin to the crushed postganglionic nerves led to a loss from both neuronal populations (40% of total neurons). This work indicates that different procedures result in selective lesion of the different neuronal populations in the ciliary ganglion

Behavioural responses of two cladocerans and two copepods exposed to fish kairomones

In natural predator-prey interactions, chemical communication is one of the most advantageous strategies for prey organisms because they can anticipate possible harm by means of phenotypic changes. This study compares the changes in the behaviour of four freshwater zooplankton species in the presence and absence of infochemicals from the same predator. The studied organisms are two copepods and two cladocerans living in highly variable freshwater environments. The analysis is focused on two predator defensive behaviours: a pre-encounter and a post-encounter response. First, we analysed the diel vertical migration (DVM) of the organisms inside 150 cm long transparent plastic tubes. Second, we used a novel hydraulic apparatus to quantify their ability to escape from a potential predator. The results revealed that the species have different behavioural patterns in the absence of infochemical. The differences were mainly in the way DVM developed and reflect their life histories and adaptive strategies relative to their natural environment. When faced with kairomones, the escape ability of the organisms was enhanced in all cases and DVM changed, although not always in agreement with the expected patterns. The interaction between each species and the multiple environmental components is discussed.Fil: Gutierrez, Marìa Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Gagneten, Ana María. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias; ArgentinaFil: Paggi, Juan Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentin

Global changes in pampean lowland streams (Argentina): Implications for biodiversity and functioning

The rivers and streams in the pampean plains are characterized by a low flow rate due to the low slope of the surrounding terrain, high levels of suspended solids, silty sediment in the benthos, and reduced rithron; the riparian forest of this region has been replaced by low-altitude grasslands. Many of these environments contain a wide coverage of aquatic reeds, both submerged and floating, making the pampas limologically extraordinary. These terrains have undergone a gradual transformation in response to the progress of urbanization and agricultural activity in recent years with a resulting loss of biodiversity, leaving only few sites that continue to reflect the original characteristics of the region. Because of human activities in combination with the global climate change, variations have occurred in biological communities that are reflected in the structure and function of populations and assemblages of algae, macrophytes, and invertebrate fauna or in the eutrophication of affected ecosystems. The objective of this article is to describe the principal limnologic characteristics of the streams that traverse the Buenos Aires Province and relate these features with the predicted future global changes for the area under study. Considering the future climate-change scenarios proposed for the pampean region, the projected increment in rainfall will affect the biological communities. Higher rainfall may enhance the erosion and generate floodings; increasing the transport of sediments, nutrients, and contaminants to the ocean and affecting the degree of water mineralization. Changes in discharge and turbidity may affect light penetration in the water column as well as its residence time. The modifications in the use of the soil will probably favor the input of nutrients. This latter effect will favor autotrophy, particularly by those species capable of generating strategies for surviving in more turbid and enriched environments. An accelerated eutrophication will change the composition of the consumers in preference to herbivores and detritivores. The increase in global population projected for the next years will demand more food, and this situation coupled with the new scenarios of climate change will lead to profound socioeconomic changes in the pampean area, implying an increase in demand for water resources and land uses.Fil: Rodrigues Capitulo, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología ; ArgentinaFil: Gomez, Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología ; ArgentinaFil: Giorgi, Adonis David Nazareno. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Luján. Departamento de Ciencias Básicas. Programa Ecología de Protistas; ArgentinaFil: Feijoó, Claudia Silvina. Universidad Nacional de Luján; Argentin