Characterization of cross-reactive CD8+ T-cell recognition of HLA-A2-restricted HIV-Gag (SLYNTVATL) and HCV-NS5b (ALYDVVSKL) epitopes in individuals infected with human immunodeficiency and hepatitis C viruses

The immunologic mechanisms underlying the faster progression of hepatitis C virus (HCV) disease in the presence of human immunodeficiency virus (HIV) coinfection are not clearly understood. T-cell cross-reactivity between HCV and influenza virus-specific epitopes has been associated with rapid progression of HCV disease (S. Urbani, B. Amadei, P. Fisicaro, M. Pilli, G. Missale, A. Bertoletti, and C. Ferrari, J. Exp. Med. 201:675-680, 2005). We asked whether T-cell cross-reactivity between HCV and HIV could exist during HCV/HIV coinfection and affect pathogenesis. Our search for amino acid sequence homology between the HCV and HIV proteomes revealed two similar HLA-A2-restricted epitopes, HIV-Gag (SLYNTVATL [HIV-SL9]) and HCV-NS5b (ALYDVVSKL [HCV-AL9]). We found that 4 out of 20 HLA-A2-positive (HLA-A2(+)) HIV-infected individuals had CD8(+) T cells that recognized both the HIV-SL9 and HCV-AL9 epitopes. However, the AL9 epitope was generally shown to be a weak agonist. Although HCV-monoinfected individuals in our study did not show AL9-specific responses, we found that about half of HCV/HIV-coinfected individuals had dual responses to both epitopes. High dual T-cell recognition among coinfected subjects was usually due to separate T-cell populations targeting each epitope, as determined by pentamer staining. The one individual demonstrating cross-reactive T cells to both epitopes showed the most advanced degree of liver disease. In coinfected individuals, we observed a positive correlation between the magnitudes of T-cell responses to both the SL9 and the AL9 epitopes, which was also positively associated with the clinical parameter of liver damage. Thus, we find that HIV infection induces T cells that can cross-react to heterologous viruses or prime for T cells that are closely related in sequence. However, the induction of cross-reactive T cells may not be associated with control of disease caused by the heterologous virus. This demonstrates that degeneracy of HIV-specific T cells may play a role in the immunopathology of HCV/HIV coinfection.     

Macrophytes in the Upper Paraná River floodplain: checklist and comparison with other large South American wetlands

Neotropical aquatic ecosystems have a rich aquatic flora. In this report, we have listed the aquatic flora of various habitats of the upper Paraná River floodplain by compiling data from literature and records of our own continuous collections conducted during the period 2007-2009. Our main purposes were to assess the macrophyte richness in the Paraná floodplain, to compare it with other South American wetlands and to assess whether the number of species recorded in South American inventories has already reached an asymptote. We recorded a total of 153 species of macrophytes in the Upper Paraná River floodplain, belonging to 100 genera and 47 families. In our comparative analysis, a clear floristic split from other South American wetlands was shown, except for the Pantanal, which is the closest wetland to the Paraná floodplain and, therefore, could be considered a floristic extension of the Pantanal. The species accumulation curve provides evidence that sampling efforts should be reinforced in order to compile a macrophyte flora census for South America. The high dissimilarity among South American wetlands, together with the lack of an asymptote in our species accumulation curve, indicates that the sampling effort needs to be increased to account for the actual species richness of macrophytes in this region.     

Exposure assessment in front of a multi-band base station antenna

This study investigates occupational exposure to electromagnetic fields in front of a multi‐band base station antenna for mobile communications at 900, 1800, and 2100 MHz. Finite‐difference time‐domain method was used to first validate the antenna model against measurement results published in the literature and then investigate the specific absorption rate (SAR) in two heterogeneous, anatomically correct human models (Virtual Family male and female) at distances from 10 to 1000 mm. Special attention was given to simultaneous exposure to fields of three different frequencies, their interaction and the additivity of SAR resulting from each frequency. The results show that the highest frequency—2100 MHz—results in the highest spatial‐peak SAR averaged over 10 g of tissue, while the whole‐body SAR is similar at all three frequencies. At distances >200 mm from the antenna, the whole‐body SAR is a more limiting factor for compliance to exposure guidelines, while at shorter distances the spatial‐peak SAR may be more limiting. For the evaluation of combined exposure, a simple summation of spatial‐peak SAR maxima at each frequency gives a good estimation for combined exposure, which was also found to depend on the distribution of transmitting power between the different frequency bands. Bioelectromagnetics 32:234–242, 2011. © 2010 Wiley‐Liss, Inc.     

The HtrA/DegP family protease MamE is a bifunctional protein with roles in magnetosome protein localization and magnetite biomineralization

Magnetotactic bacteria contain nanometre-sized, membrane-bound organelles, called magnetosomes, which are tasked with the biomineralization of small crystals of the iron oxide magnetite allowing the organism to use geomagnetic field lines for navigation. A key player in this process is the HtrA/DegP family protease MamE. In its absence, Magnetospirillum magneticum str AMB-1 is able to form magnetosome membranes but not magnetite crystals, a defect previously linked to the mislocalization of magnetosome proteins. In this work we use a directed genetic approach to find that MamE, and another predicted magnetosome-associated protease, MamO, likely function as proteases in vivo. However, as opposed to the complete loss of mamE where no biomineralization is observed, the protease-deficient variant of this protein still supports the initiation and formation of small, 20 nm-sized crystals of magnetite, too small to hold a permanent magnetic dipole moment. This analysis also reveals that MamE is a bifunctional protein with a protease-independent role in magnetosome protein localization and a protease-dependent role in maturation of small magnetite crystals. Together, these results imply the existence of a previously unrecognized 'checkpoint' in biomineralization where MamE moderates the completion of magnetite formation and thus committal to magneto-aerotaxis as the organism's dominant mode of navigating the environment.     

A novel iron‐ and copper‐binding protein in the Lyme disease spirochaete

Iron and copper are transition metals that can be toxic to cells due to their abilities to react with peroxide to generate hydroxyl radical. Ferritins and metallothioneins are known to sequester intracellular iron and copper respectively. The Lyme disease pathogen Borrelia burgdorferi does not require iron, but its genome encodes a ferritin‐like Dps (D NA‐binding p rotein from s tarved bacteria) molecule, which has been shown to be important for the spirochaete's persistence in the tick and subsequent transmission to a new host. Here, we show that the c arboxyl‐terminal c ysteine‐r ich (CCR) domain of this protein functions as a copper‐binding metallothionein. This novel fusion between Dps and metallothionein is unique to and conserved in all Borrelia species. We term this molecule BicA for B orrelia i ron‐ and c opper‐binding protein A . An isogenic mutant lacking BicA had significantly reduced levels of iron and copper and was more sensitive to iron and copper toxicity than its parental strain. Supplementation of the medium with iron or copper rendered the spirochaete more susceptible to peroxide killing. These data suggest that an important function of BicA is to detoxify excess iron and copper the spirochaete may encounter during its natural life cycle through a tick vector and a vertebrate host.     

iDNA screening: Disease vectors as vertebrate samplers

In the current context of global change and human‐induced biodiversity decline, there is an urgent need for developing sampling approaches able to accurately describe the state of biodiversity. Traditional surveys of vertebrate fauna involve time‐consuming and skill‐demanding field methods. Recently, the use of DNA derived from invertebrate parasites (leeches and blowflies) was suggested as a new tool for vertebrate diversity assessment. Bloodmeal analyses of arthropod disease vectors have long been performed to describe their feeding behaviour, for epidemiological purposes. On the other hand, this existing expertise has not yet been applied to investigate vertebrate fauna per se. Here, we evaluate the usefulness of hematophagous dipterans as vertebrate samplers. Blood‐fed sand flies and mosquitoes were collected in Amazonian forest sites and analysed using high‐throughput sequencing of short mitochondrial markers. Bloodmeal identifications highlighted contrasting ecological features and feeding behaviour among dipteran species, which allowed unveiling arboreal and terrestrial mammals of various body size, as well as birds, lizards and amphibians. Additionally, lower vertebrate diversity was found in sites undergoing higher levels of human‐induced perturbation. These results suggest that, in addition to providing precious information on disease vector host use, dipteran bloodmeal analyses may represent a useful tool in the study of vertebrate communities. Although further effort is required to validate the approach and consider its application to large‐scale studies, this first work opens up promising perspectives for biodiversity monitoring and eco‐epidemiology.     

Curcumin treatment alleviates the effects of glutathione depletion in vitro and in vivo: therapeutic implications for Parkinson's disease explained via in silico studies

Oxidative stress has been implicated in the degeneration of dopaminergic neurons in the substantia nigra (SN) of Parkinson's disease (PD) patients. An important biochemical feature of presymptomatic PD is a significant depletion of the thiol antioxidant glutathione (GSH) in these neurons resulting in oxidative stress, mitochondrial dysfunction, and ultimately cell death. We have earlier demonstrated that curcumin, a natural polyphenol obtained from turmeric, protects against peroxynitrite-mediated mitochondrial dysfunction both in vitro and in vivo. Here we report that treatment of dopaminergic neuronal cells and mice with curcumin restores depletion of GSH levels, protects against protein oxidation, and preserves mitochondrial complex I activity which normally is impaired due to GSH loss. Using systems biology and dynamic modeling we have explained the mechanism of curcumin action in a model of mitochondrial dysfunction linked to GSH metabolism that corroborates the major findings of our experimental work. These data suggest that curcumin has potential therapeutic value for neurodegenerative diseases involving GSH depletion-mediated oxidative stress.     

Features and conservation of the Brazilian Pantanal wetland

The Pantanal is a 140,000 km² sedimentary floodplain in western Brazil and one of the largest wetlands in the world. The main landscapes and phytophysiognomies, according to flood origin, are briefly described and some of the characteristic plant species are mentioned: (a) river flood (1–5 m) on clayey eutrophic soils with gallery forests, pioneer forests and scrub, Tabebuia and Copernicia parks, seasonal swamps, grasslands and oxbow lakes; and (b) rain flood (10–80 cm) mainly on dystrophic sandy soils (72% of the total area) with savanna (cerrado) grasslands and woodlands, with or without ponds. Regulating factors of the vegetation such as wet-and-dry cycle and management are considered. Dynamics of the vegetation, in particular the aquatic types, are shortly depicted. The role of grazing for conservation is discussed, and we suggest that 200 years of cattle ranching apparently did not cause major changes in the vegetation, except turning tall grass into short swards, as the domestic herd found a nearly empty niche. However, severe threats to the flora and fauna of the Pantanal originate outside the floodplain. Siltation of the Taquari river is pointed out as the worst environmental problem, changing the hydrology (wet-and-dry to wet), fauna and flora, e.g. eliminating riparian forest.This revised version was published online in March 2005 with corrections to the issue cover date.