Anatomy and systematics of the diplodocoid Amphicoelias altus supports high sauropod dinosaur diversity in the Upper Jurassic Morrison Formation of the USA

Sauropod dinosaurs were an abundant and diverse component of the Upper Jurassic Morrison Formation of the USA, with 24 currently recognized species. However, some authors consider this high diversity to have been ecologically unviable and the validity of some species has been questioned, with suggestions that they represent growth series (ontogimorphs) of other species. Under this scenario, high sauropod diversity in the Late Jurassic of North America is greatly overestimated. One putative ontogimorph is the enigmatic diplodocoid Amphicoelias altus, which has been suggested to be synonymous with Diplodocus. Given that Amphicoelias was named first, it has priority and thus Diplodocus would become its junior synonym. Here, we provide a detailed re-description of A. altus in which we restrict it to the holotype individual and support its validity, based on three autapomorphies. Constraint analyses demonstrate that its phylogenetic position within Diplodocoidea is labile, but it seems unlikely that Amphicoelias is synonymous with Diplodocus. As such, our re-evaluation also leads us to retain Diplodocus as a distinct genus. There is no evidence to support the view that any of the currently recognized Morrison sauropod species are ontogimorphs. Available data indicate that sauropod anatomy did not dramatically alter once individuals approached maturity. Furthermore, subadult sauropod individuals are not prone to stemward slippage in phylogenetic analyses, casting doubt on the possibility that their taxonomic affinities are substantially misinterpreted. An anatomical feature can have both an ontogenetic and phylogenetic signature, but the former does not outweigh the latter when other characters overwhelmingly support the affinities of a taxon. Many Morrison Formation sauropods were spatio-temporally and/or ecologically separated from one another. Combined with the biases that cloud our reading of the fossil record, we contend that the number of sauropod dinosaur species in the Morrison Formation is currently likely to be underestimated, not overestimated

Cysteine 230 is essential for the structure and activity of the cytotoxic ligand TRAIL.

Unlike other tumor necrosis factor family members, the cytotoxic ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo-2L contains an unpaired cysteine residue (Cys(230)) in its receptor-binding domain. Here we show that the biological activity of both soluble recombinant TRAIL and cell-associated, full-length TRAIL is critically dependent on the presence of Cys(230). Mutation of Cys(230) to alanine or serine strongly affected its ability to kill target cells. Binding to its receptors was decreased by at least 200-fold, and the stability of its trimeric structure was reduced. In recombinant TRAIL, Cys(230) was found engaged either in interchain disulfide bridge formation, resulting in poorly active TRAIL, or in the chelation of one zinc atom per TRAIL trimer in the active, pro-apoptotic form of TRAIL

GridCertLib: a Single Sign-on Solution for Grid Web Applications and Portals

This paper describes the design and implementation of GridCertLib, a Java library leveraging a Shibboleth-based authentication infrastructure and the SLCS online certificate signing service, to provide short-lived X.509 certificates and Grid proxies. The main use case envisioned for GridCertLib, is to provide seamless and secure access to Grid/X.509 certificates and proxies in web applications and portals: when a user logs in to the portal using Shibboleth authentication, GridCertLib can automatically obtain a Grid/X.509 certificate from the SLCS service and generate a VOMS proxy from it. We give an overview of the architecture of GridCertLib and briefly describe its programming model. Its application to some deployment scenarios is outlined, as well as a report on practical experience integrating GridCertLib into portals for Bioinformatics and Computational Chemistry applications, based on the popular P-GRADE and Django softwares.Comment: 18 pages, 1 figure; final manuscript accepted for publication by the "Journal of Grid Computing

Clara cell protein and surfactant proteinB in garbage collectors and in wastewater workers exposed to bioaerosols

Objectives: Inhalation of bioaerosols has been hypothesised to cause "toxic pneumonitis” that should increase lung epithelial permeability at the bronchioloalveolar level. Serum Clara cell protein (CC16) and serum surfactant proteinB (SPB) have been proposed as sensitive markers of lung epithelial injury. This study was aimed at looking for increased lung epithelial permeability by determining CC16 and SPB in workers exposed to bioaerosols from wastewater or garbage. Methods: Subjects (778 wastewater, garbage and control workers; participation 61%) underwent a medical examination, lung function tests [American Thoracic Society (ATS) criteria], and determination of CC16 and SPB. Symptoms of endotoxin exposure and several potential confounders (age, gender, smoking, kidney function, obesity) were looked for. Results were examined with multiple linear or logistic regression. Results: Exposure to bioaerosols increased CC16 concentration in the wastewater workers. No effect of exposure on SPB was found. No clue to work-related respiratory diseases was found. Conclusions: The increase in CC16 in serum supports the hypothesis that bioaerosols cause subclinical "toxic pneumonitis”, even at low exposur

ER stress activates the NLRP3 inflammasome via an UPR-independent pathway

Uncontrolled endoplasmic reticulum (ER) stress responses are proposed to contribute to the pathology of chronic inflammatory diseases such as type 2 diabetes or atherosclerosis. However, the connection between ER stress and inflammation remains largely unexplored. Here, we show that ER stress causes activation of the NLRP3 inflammasome, with subsequent release of the pro-inflammatory cytokine interleukin-1β. This ER-triggered proinflammatory signal shares the same requirement for reactive oxygen species production and potassium efflux compared with other known NLRP3 inflammasome activators, but is independent of the classical unfolded protein response (UPR). We thus propose that the NLRP3 inflammasome senses and responds to ER stress downstream of a previously uncharacterized ER stress response signaling pathway distinct from the UPR, thus providing mechanistic insight to the link between ER stress and chronic inflammatory diseases

Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates NF-kappaB transcription factor and c-Jun N-terminal kinase.

We have previously reported on the death effector domain containing E8 gene product from equine herpesvirus-2, designated FLICE inhibitory protein (v-FLIP), and on its cellular homologue, c-FLIP, which inhibit the activation of caspase-8 by death receptors. Here we report on the structure and function of the E10 gene product of equine herpesvirus-2, designated v-CARMEN, and on its cellular homologue, c-CARMEN, which contain a caspase-recruiting domain (CARD) motif. c-CARMEN is highly homologous to the viral protein in its N-terminal CARD motif but differs in its C-terminal extension. v-CARMEN and c-CARMEN interact directly in a CARD-dependent manner yet reveal different binding specificities toward members of the tumor necrosis factor receptor-associated factor (TRAF) family. v-CARMEN binds to TRAF6 and weakly to TRAF3 and, upon overexpression, potently induces the c-Jun N-terminal kinase (JNK), p38, and nuclear factor (NF)-kappaB transcriptional pathways. c-CARMEN or truncated versions thereof do not appear to induce JNK and NF-kappaB activation by themselves, nor do they affect the JNK and NF-kappaB activating potential of v-CARMEN. Thus, in contrast to the cellular homologue, v-CARMEN may have additional properties in its unique C terminus that allow for an autonomous activator effect on NF-kappaB and JNK. Through activation of NF-kappaB, v-CARMEN may regulate the expression of the cellular and viral genes important for viral replication

Surfactant protein-D and exposure to bioaerosols in wastewater and garbage workers

Purpose: Bioaerosols and their constituents, such as endotoxins, are capable of causing an inflammatory reaction at the level of the lung-blood barrier, which becomes more permeable. Thus, it was hypothesized that occupational exposure to bioaerosols can increase leakage of surfactant protein-D (SP-D), a lung-specific protein, into the bloodstream. Methods: SP-D was determined by ELISA in 316 wastewater workers, 67 garbage collectors, and 395 control subjects. Exposure was assessed with four interview-based indicators and by preliminary endotoxin measurements using the Limulus amoebocyte lysate assay. Influence of exposure on serum SP-D was assessed by multiple linear regression considering smoking, glomerular function, lung diseases, obesity, and other confounders. Results: Overall, mean exposure levels to endotoxins were below 100EU/m3. However, special tasks of wastewater workers caused higher endotoxin exposure. SP-D concentration was slightly increased in this occupational group and associated with the occurrence of splashes and contact to raw sewage. No effect was found in garbage collectors. Smoking increased serum SP-D. No clinically relevant correlation between spirometry results and SP-D concentrations appeared. Conclusions: These results support the hypothesis that inhalation of bioaerosols, even at low concentrations, has a subclinical effect on the lung-blood barrier, the permeability of which increases without associated spirometric change

Hodgkin's lymphoma in remission after first-line therapy: which patients need FDG-PET/CT for follow-up?

Background: The purpose of the study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) during follow-up of patients with Hodgkin's lymphoma. Patients and methods: Patients in complete remission or an unconfirmed complete remission after first-line therapy who received FDG-PET/CT during their follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in case of recurrence. Results: Overall, 134 patients were analyzed. Forty-two (31.3%) patients had a recurrence. The positive predictive value of FDG-PET/CT was 0.98. Single-factor analysis identified morphological residual mass [P = 0.0005, hazard ratio (HR) 3.4, 95% confidence interval (CI) 1.7-6.6] and symptoms (P 24 months). Conclusions: Asymptomatic patients without morphological residues and an early stage of disease do not need a routine FDG-PET/CT for follow-up. Asymptomatic patients with morphological residues should receive routine follow-up FDG-PET/CT for the first 24 months. Only patients with advanced initial stage do need a routine follow-up FDG-PET/CT beyond 24 month

The anti-apoptotic factor Bcl-2 can functionally substitute for the B cell survival but not for the marginal zone B cell differentiation activity of BAFF.

The TNF family ligand B cell-activating factor (BAFF, BLyS, TALL-1) is an essential factor for B cell development. BAFF binds to three receptors, BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA), but only BAFF-R is required for successful survival and maturation of splenic B cells. To test whether the effect of BAFF is due to the up-regulation of anti-apoptotic factors, TACI-Ig-transgenic mice, in which BAFF function is inhibited, were crossed with transgenic mice expressing FLICE-inhibitory protein (FLIP) or Bcl-2 in the B cell compartment. FLIP expression did not rescue B cells, while enforced Bcl-2 expression restored peripheral B cells and the ability to mount T-dependent antibody responses. However, many B cells retained immaturity markers and failed to express normal amounts of CD21. Marginal zone B cells were not restored and the T-independent IgG3, but not IgM, response was impaired in the TACI-IgxBcl-2 mice. These results suggest that BAFF is required not only to inhibit apoptosis of maturating B cells, but also to promote differentiation events, in particular those leading to the generation of marginal zone B cells