Haloalkaliphilic spore-forming sulfidogens from soda lake sediments and description of Desulfitispora alkaliphila gen. nov., sp. nov.

An anaerobic enrichment with pyruvate as electron donor and thiosulfate at pH 10 and 0.6 M Na+ inoculated with pasteurized soda lake sediments resulted in a sulfidogenic coculture of two morphotypes of obligately anaerobic haloalkaliphilic endospore-forming clostridia, which were further isolated in pure culture. Strain AHT16 was a thin long rod able to ferment sugars and pyruvate and to respire H2, formate and pyruvate using thiosulfate and fumarate as electron acceptors and growing optimally at pH 9.5. Thiosulfate was reduced incompletely to sulfide and sulfite. The strain was closely related (99% sequence similarity) to a peptolytic alkaliphilic clostridium Natronincola peptidovorans. Strain AHT17 was a short rod with a restricted respiratory metabolism, growing with pyruvate and lactate as electron donor and sulfite, thiosulfate and elemental sulfur as electron acceptors with a pH optimum 9.5. Thiosulfate was reduced completely via sulfite to sulfide. The ability of AHT17 to use sulfite explained the stability of the original coculture of the two clostridia—one member forming sulfite from thiosulfate and another consuming it. Strain AHT17 formed an independent deep phylogenetic lineage within the Clostridiales and is proposed as a new genus and species Desulfitisporum alkaliphilum gen. nov., sp. nov. (=DSM 22410T = UNIQEM U794T)

Copper Deficiency Induced Emphysema Is Associated with Focal Adhesion Kinase Inactivation

Background: Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1a) dependent vascular endothelial growth factor (VEGF) expression, and is also required for the activity of lysyl oxidase (LOX) to effect matrix protein crosslinking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis) via inactivation of focal adhesion kinase (FAK). Methodology: To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the inhibitor of auto-phosphorylation of FAK, 1,2,4,5-benzenetetraamine tetrahydrochloride (1,2,4,5-BT) or FAK small interfering RNA (siRNA). Principal Findings: Copper depletion caused emphysematous changes, decreased HIF-1a activity, and downregulated VEGF expression in the rat lungs. Cleaved caspase-3, caspase-8 and Bcl-2 interacting mediator of cell death (Bim) expression was increased, and the phosphorylation of FAK was decreased in copper depleted rat lungs. Administration of 1,2,4,5-BT and FAK siRNA caused emphysematous lung destruction associated with increased expression of cleaved capase-3, caspase-8 and Bim. Conclusions: These data indicate that copper-dependent mechanisms contribute to the pathogenesis of emphysema

In Vitro and In Vivo Efficacy of Ether Lipid Edelfosine against Leishmania spp. and SbV-Resistant Parasites

Leishmaniasis represents a major international health problem, has a high morbidity and mortality rate, and is classified as an emerging and uncontrolled disease by the World Health Organization. The migration of population from endemic to nonendemic areas, and tourist activities in endemic regions are spreading the disease to new areas. Unfortunately, treatment of leishmaniasis is far from satisfactory, with only a few drugs available that show significant side-effects. Here, we show in vitro and in vivo evidence for the antileishmanial activity of the ether phospholipid edelfosine, being effective against a wide number of Leishmania spp. causing cutaneous, mucocutaneous and visceral leishmaniasis. Our experimental mouse and hamster models demonstrated not only a significant antileishmanial activity of edelfosine oral administration against different wild-type Leishmania spp., but also against parasites resistant to pentavalent antimonials, which constitute the first line of treatment worldwide. In addition, edelfosine exerted a higher antileishmanial activity and a lower proneness to generate drug resistance than miltefosine, the first drug against leishmaniasis that can be administered orally. These data, together with our previous findings, showing an anti-inflammatory action and a very low toxicity profile, suggest that edelfosine is a promising orally administered drug for leishmaniasis, thus warranting clinical evaluation

Impact of jet-production data on the next-to-next-to-leading-order determination of HERAPDF2.0 parton distributions

The HERAPDF2.0 ensemble of parton distribution functions (PDFs) was introduced in 2015. The final stage is presented, a next-to-next-to-leading-order (NNLO) analysis of the HERA data on inclusive deep inelastic ep scattering together with jet data as published by the H1 and ZEUS collaborations. A perturbative QCD fit, simultaneously of αs(M2Z) and the PDFs, was performed with the result αs(M2Z)=0.1156±0.0011 (exp) +0.0001−0.0002 (model +parameterisation) ±0.0029 (scale). The PDF sets of HERAPDF2.0Jets NNLO were determined with separate fits using two fixed values of αs(M2Z), αs(M2Z)=0.1155 and 0.118, since the latter value was already chosen for the published HERAPDF2.0 NNLO analysis based on HERA inclusive DIS data only. The different sets of PDFs are presented, evaluated and compared. The consistency of the PDFs determined with and without the jet data demonstrates the consistency of HERA inclusive and jet-production cross-section data. The inclusion of the jet data reduced the uncertainty on the gluon PDF. Predictions based on the PDFs of HERAPDF2.0Jets NNLO give an excellent description of the jet-production data used as input

The embryo as moral work object: PGD/IVF staff views and experiences

Copyright @ 2008 the authors. This article is available in accordance with the Creative Commons Deed, Attribution 2.5, see http://creativecommons.org/licenses/by-nc-nd/2.5/deed.en_CA.We report on one aspect of a study that explored the views and experiences of practitioners and scientists on social, ethical and clinical dilemmas encountered when working in the field of preimplantation genetic diagnosis (PGD) for serious genetic disorders. The study produced an ethnography based on observation, interviews and ethics discussion groups with staff from two PGD/IVF Units in the UK. We focus here on staff perceptions of work with embryos that entails disposing of ‘affected’ or ‘spare’ embryos or using them for research. A variety of views were expressed on the ‘embryo question’ in contrast to polarised media debates. We argue that the prevailing policy acceptance of destroying affected embryos, and allowing research on embryos up to 14 days leaves some staff with rarely reported, ambivalent feelings. Staff views are under-researched in this area and we focus on how they may reconcile their personal moral views with the ethical framework in their field. Staff construct embryos in a variety of ways as ‘moral work objects’. This allows them to shift attention between micro-level and overarching institutional work goals, building on Casper's concept of ‘work objects’ and focusing on negotiation of the social order in a morally contested field.The Wellcome Trust Biomedical Ethics Programme, who funded the projects‘Facilitating choice, framing choice: the experience of staff working in pre-implantation genetic diagnosis’ (no: 074935), and ‘Ethical Frameworks for Embryo Donation:the views and practices of IVF/PGD staff’ (no: 081414)

Genomic reconstruction of a novel, deeply branched sediment archaeal phylum with pathways for acetogenesis and sulfur reduction

Marine and estuary sediments contain a variety of uncultured archaea whose metabolic and ecological roles are unknown. De novo assembly and binning of high-throughput metagenomic sequences from the sulfate–methane transition zone in estuary sediments resulted in the reconstruction of three partial to near-complete (2.4–3.9 Mb) genomes belonging to a previously unrecognized archaeal group. Phylogenetic analyses of ribosomal RNA genes and ribosomal proteins revealed that this group is distinct from any previously characterized archaea. For this group, found in the White Oak River estuary, and previously registered in sedimentary samples, we propose the name ‘Thorarchaeota'. The Thorarchaeota appear to be capable of acetate production from the degradation of proteins. Interestingly, they also have elemental sulfur and thiosulfate reduction genes suggesting they have an important role in intermediate sulfur cycling. The reconstruction of these genomes from a deeply branched, widespread group expands our understanding of sediment biogeochemistry and the evolutionary history of Archaea

Hydrocarbon Degradation and Response of Seafloor Sediment Bacterial Community in the Northern Gulf of Mexico to Light Louisiana Sweet Crude Oil

The Deepwater Horizon (DWH) blowout resulted in the deposition to the seafloor of up to 4.9% of 200 million gallons of oil released into the Gulf of Mexico. The petroleum hydrocarbon concentrations near the wellhead were high immediately after the spill, but returned to background levels a few years after the spill. Microbial communities in the seafloor are thought to be responsible for the degradation of hydrocarbons, however, our knowledge is primarily based upon gene diversity surveys and hydrocarbon concentration in field sediment samples. Here, we investigated the oil degradation potential and changes in bacterial community by amending seafloor sediment collected near the DWH site with crude oil and both oil and Corexit dispersant. Polycyclic aromatic hydrocarbons were rapidly degraded during the first 30 days of incubation, while alkanes were degraded more slowly. With the degradation of hydrocarbons, the relative abundances of Colwelliaceae, Alteromonadaceae, Methylococales, Alcanivorax, Bacteriovorax, and Phaeobacter increased remarkably. However, the abundances of oil-degrading bacteria changed with oil chemistry. Colwelliaceae decreased with increasing oil degradation, whereas Alcanivorax and Methylococcales increased considerably. We assembled seven genomes from the metagenome, including ones belonging to Colwellia, Alteromonadaceae, Rhodobacteraceae, the newly reported genus Woeseia, and candidate phylum NC10, all of which possess a repertoire of genes for hydrocarbon degradation. Moreover, genes related to hydrocarbon degradation were highly enriched in the oiled treatment, suggesting that the hydrocarbons were biodegraded, and that the indigenous microflora have a remarkable potential for the natural attenuation of spilled oil in the deep-sea surface sediment