The Nef-mediated AIDS-like disease of CD4C/human immunodeficiency virus transgenic mice is associated with increased Fas/FasL expression on T cells and T-cell death but is not prevented in Fas-, FasL-, tumor necrosis factor receptor 1-, or interleukin-1beta-converting enzyme-deficient or Bcl2-expressing transgenic mice

CD4(+)- and CD8(+)-T-cell death is a frequent immunological dysfunction associated with the development of human AIDS. We studied a murine model of AIDS, the CD4C/HIV transgenic (Tg) mouse model, to assess the importance of the apoptotic pathway in human immunodeficiency virus type 1 (HIV-1) pathogenesis. In these Tg mice, Nef is the major determinant of the disease and is expressed in immature and mature CD4(+) T cells and in cells of the macrophage/myeloid lineage. We report here a novel AIDS-like phenotype: enhanced death, most likely by apoptosis (as assessed by 7-aminoactinomycin D and annexin V/propidium iodide staining), of Tg thymic and peripheral CD4(+) and CD8(+) T cells. The Tg CD4(+) and CD8(+) T cells were also more susceptible to cell death after activation in vitro in mixed lymph node (LN) cultures. However, activation-induced cell death was not higher in Tg than in non-Tg-purified CD4(+) T cells. In addition, expression of Fas and FasL, assessed by flow cytometry, was increased in CD4(+) and CD8(+) T cells from Tg mice compared to that of non-Tg littermates. Despite the enhanced expression of Fas and FasL on Tg CD4(+) and CD8(+) T cells, Fas (lpr/lpr) and FasL (gld/gld) mutant CD4C/HIV Tg mice developed an AIDS-like disease indistinguishable from lpr/+ and gld/+ CD4C/HIV Tg mice, including loss of CD4(+) T cells. Similarly, CD4C/HIV Tg mice homozygous for mutations of two other genes implicated in cell death (interleukin-1beta-converting enzyme [ICE], tumor necrosis factor receptor 1 [TNFR-1]) developed similar AIDS-like disease as their respective heterozygous controls. Moreover, the double-Tg mice from a cross between the Bcl2/Wehi25 and CD4C/HIV Tg mice showed no major protection against disease. These results represent genetic evidence for the dispensable role of Fas, FasL, ICE, and TNFR-1 on the development of both T-cell loss and organ disease of these Tg mice. They also provide compelling evidence on the lack of protection by Bcl2 against Tg CD4(+)-T-cell death. In view of the high resemblance between numerous phenotypes observed in the CD4C/HIV Tg mice and in human AIDS, our findings are likely to be relevant for the human disease.     

Pyrrolylbenzothiazole Derivatives as Aldose Reductase Inhibitors

Abstract

2,2-Dimethyl-4-hydroxy-4-androstene-3,17-dione (4) has been synthesized and has been shown to be a powerful competitive inhibitor of aromatase (K_i = 11.4nM). However, compound 4 does not cause time-dependent loss of enzyme activity, in contrast to the unmethylated parent compound, 4-OHA.     

Origin and hidden diversity within the poorly known Galápagos snake radiation (Serpentes: Dipsadidae)

Galápagos snakes are among the least studied terrestrial vertebrates of the Archipelago. Here, we provide a phylogenetic analysis and a time calibrated tree for the group, based on a sampling of the major populations known to occur in the Archipelago. Our study revealed the presence of two previously unknown species from Santiago and Rábida Islands, and one from Tortuga, Isabela, and Fernandina. We also recognize six additional species of Pseudalsophis in the Galápagos Archipelago (Pseudalsophis biserialis from San Cristobal, Floreana and adjacent islets; Pseudalsophis hoodensis from Española and adjacent islets; Pseudalsophis dorsalis from Santa Cruz, Baltra, Santa Fé, and adjacent islets; Pseudalsophis occidentalis from Fernandina, Isabela, and Tortuga; Pseudalsophis slevini from Pinzon, and Pseudalsophis steindachneri from Baltra, Santa Cruz and adjacent islets). Our time calibrated tree suggests that the genus Pseudalsophis colonized the Galápagos Archipelago through a single event of oceanic dispersion from the coast of South America that occurred at approximately between 6.9?Ma and 4.4?Ma, near the Miocene/Pliocene boundary.www.zoobank.org/urn:lsid:zoobank.org:pub:2679FD19-01E5-48FE-A0DA-A88FF145DE56     

Gene-sequence-based criteria for species definition in bacteriology: the Bartonella paradigm

The definition of new species is currently based on polyphasic classification that includes both determination of phenotypic characteristics and DNA-DNA homology. However, none of these techniques is convenient for the rapid characterization of fastidious or non-culturable bacteria. Using sequences available in the GenBank database, we compared the similarities of gene fragments among the currently recognized Bartonella species. This comparison led to both the definition of similarity values that discriminated Bartonella at the species level and assessment of the relative discriminatory power of each gene examined. In this perspective, rpoB and gltA were found to be the most potent.     

Influence of traffic variations on exposure to wireless signals in realistic environments

In this article, the general public daily exposure to broadcast signals and Global System for Mobile Communications (GSM) or Universal Mobile Telecommunications System (UMTS) mobile telephone signals in indoor areas is investigated. Temporal variations and traffic distributions during a day at different indoor sites in urban and rural zones are presented. The goal is to analyze the real exposure compared to the maximum assessment imposed by radio protection standards and to characterize the ratio between daily and maximum theoretical values. Hence, a realistic maximum is proposed based on the statistical analysis performed using measurements. Broadcast signals remain constant over the day so they are best fitted with a Normal distribution while the mobile telephone signals depend on the traffic demand during the day so they fit a three‐Gaussian distribution model. A general mask is also constructed for underlining the maximum equivalent active traffic for different periods in the day. Also, relations between the mean values over 24 h, the realistic maximal values (at 99%) and the maximal theoretical values are presented. The realistic maximum is also presented with a sliding time average of 6 min applied to the measurements in accordance with international standards. An extrapolation factor is given for the different systems to easily assess the maximum values starting from an instantaneous measurement. The extrapolation factor is also given for a broadband measurement to estimate the maximum potential exposure during the day. Bioelectromagnetics 33:288–297, 2012. © 2011 Wiley Periodicals, Inc.     

Ribosome quality control antagonizes the activation of the integrated stress response on colliding ribosomes

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CagA of Helicobacter pylori alters the expression and cellular distribution of host proteins involved in cell signaling

To expand our knowledge of Helicobacter pylori virulence mechanisms, we used iTRAQ (isobaric tagging reagents for relative and absolute quantification)-based proteomic analysis to investigate the effect of H. pylori on gastric AGS tissue culture cells. In particular, we were interested in finding out which effects of H. pylori were dependent on the cytotoxins CagA and VacA. Protein analysis was restricted to detergent-resistant membranes (DRMs), because both toxins were described previously to localize in lipid raft-like domains. Using H. pylori wild type and two isogenic mutants, DeltacagA and DeltavacA, we identified a total of 21 proteins that were either increased or decreased in the DRMs due to bacterial infection. The effect on three of these proteins, ezrin, syndecan-4 and Rab11-FIP1, were furthermore dependent on CagA. Because these proteins have been implicated in cell migration, adhesion and polarity, they might act as important mediators of CagA cytotoxicity.     

The development of the skull in Acrochordus granulatus (Schneider) (Reptilia: Serpentes), with special consideration of the otico-occipital complex

The skull of Acrochordus has been characterized by the absence of a crista circumfenestralis (a synapomorphy shared by all snakes), and by the absence of a recessus scalae tympani that in other squamates forms by subdivision of the embryonic metotic fissure. These traits have variably been identified as either plesiomorphic or paedomorphic. The study of the development of the osteocranium in a series of cleared and stained embryos of Acrochordus shows a close correspondence to the development of the skull in other snakes. The exception is the formation of the postorbital from two ossification centers. The significance of this observation, which might suggest the embryonic fusion of a postfrontal with a postorbital, remains enigmatic, as it is based on one side only of the skull of a single specimen. By contrast, a rudimentary and modified crista circumfenestralis can be identified in the skull of Acrochordus. Furthermore, absence of a recessus scalae tympani is not due to an undivided fissura metotica, but results from the obliteration of the anterior part of the metotic fissure instead. With respect to this character, Acrochordus is neither plesiomorphic, nor paedomorphic, but autapomorphic. This interpretation of the skull of Acrochordus is compatible with the sister-group relationships this genus shares with colubroid snakes.