T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia

Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease

Microbial Ecology of Lake Kivu

peer reviewedWe review available data on archaea, bacteria and small eukaryotes in an attempt to provide a general picture of microbial diversity, abundances and microbe-driven processes in Lake Kivu surface and intermediate waters (ca. 0–100 m). The various water layers present contrasting physical and chemical properties and harbour very different microbial communities supported by the vertical redox structure. For instance, we found a clear vertical segregation of archaeal and bacterial assemblages between the oxic and the anoxic zone of the surface waters. The presence of specific bacterial (e.g. Green Sulfur Bacteria) and archaeal (e.g. ammonia-oxidising archaea) communities and the prevailing physico-chemical conditions point towards the redoxcline as the most active and metabolically diverse water layer. The archaeal assemblage in the surface and intermediate water column layers was mainly composed by the phylum Crenarchaeota , by the recently defined phylum Thaumarchaeota and by the phylum Euryarchaeota . In turn, the bacterial assemblage comprised mainly ubiquitous members of planktonic assemblages of freshwater environments (Actinobacteria, Bacteroidetes and Betaproteobacteria among others) and other less commonly retrieved phyla (e.g. Chlorobi, Clostridium and Deltaproteobacteria). The community of small eukaryotes (<5 µm) mainly comprised Stramenopiles , Alveolata , Cryptophyta , Chytridiomycota , Kinetoplastea and Choanoflagellida, by decreasing order of richness. The total prokaryotic abundance ranged between 0.5 × 10^6 and 2.0 × 10^6 cells mL−1 , with maxima located in the 0–20 m layer, while phycoerythrin-rich Synechococcus-like picocyanobacteria populations were comprised between 0.5 × 10^5 and 2.0 × 10^5 cells mL−1 in the same surface layer. Brown-coloured species of Green Sulfur Bacteria permanently developed at 11m depth in Kabuno Bay and sporadically in the anoxic waters of the lower mixolimnion of the main basin. The mean bacterial production was estimated to 336 mg C m−2 day−1 . First estimates of the re-assimilation by bacterioplankton of dissolved organic matter excreted by phytoplankton showed high values of dissolved primary production (ca. 50% of total production). The bacterial carbon demand can totally be fuelled by phytoplankton production. Overall, recent studies have revealed a high microbial diversity in Lake Kivu, and point towards a central role of microbes in the biogeochemical and ecological functioning of the surface layers, comprising the mixolimnion and the upper chemocline

Solubility trapping in formation water as dominant CO2 sink in natural gas fields

Injecting CO2 into deep geological strata is proposed as a safe and economically favourable means of storing CO2 captured from industrial point sources1, 2, 3. It is difficult, however, to assess the long-term consequences of CO2 flooding in the subsurface from decadal observations of existing disposal sites1, 2. Both the site design and long-term safety modelling critically depend on how and where CO2 will be stored in the site over its lifetime2, 3, 4. Within a geological storage site, the injected CO2 can dissolve in solution or precipitate as carbonate minerals. Here we identify and quantify the principal mechanism of CO2 fluid phase removal in nine natural gas fields in North America, China and Europe, using noble gas and carbon isotope tracers. The natural gas fields investigated in our study are dominated by a CO2 phase and provide a natural analogue for assessing the geological storage of anthropogenic CO2 over millennial timescales1, 2, 5, 6. We find that in seven gas fields with siliciclastic or carbonate-dominated reservoir lithologies, dissolution in formation water at a pH of 5–5.8 is the sole major sink for CO2. In two fields with siliciclastic reservoir lithologies, some CO2 loss through precipitation as carbonate minerals cannot be ruled out, but can account for a maximum of 18 per cent of the loss of emplaced CO2. In view of our findings that geological mineral fixation is a minor CO2 trapping mechanism in natural gas fields, we suggest that long-term anthropogenic CO2 storage models in similar geological systems should focus on the potential mobility of CO2 dissolved in wate

Thermophilic anaerobic oxidation of methane by marine microbial consortia

The anaerobic oxidation of methane (AOM) with sulfate controls the emission of the greenhouse gas methane from the ocean floor. AOM is performed by microbial consortia of archaea (ANME) associated with partners related to sulfate-reducing bacteria. In vitro enrichments of AOM were so far only successful at temperatures less than or equal to25 °C; however, energy gain for growth by AOM with sulfate is in principle also possible at higher temperatures. Sequences of 16S rRNA genes and core lipids characteristic for ANME as well as hints of in situ AOM activity were indeed reported for geothermally heated marine environments, yet no direct evidence for thermophilic growth of marine ANME consortia was obtained to date. To study possible thermophilic AOM, we investigated hydrothermally influenced sediment from the Guaymas Basin. In vitro incubations showed activity of sulfate-dependent methane oxidation between 5 and 70 °C with an apparent optimum between 45 and 60 °C. AOM was absent at temperatures greater than or equal to75 °C. Long-term enrichment of AOM was fastest at 50 °C, yielding a 13-fold increase of methane-dependent sulfate reduction within 250 days, equivalent to an apparent doubling time of 68 days. The enrichments were dominated by novel ANME-1 consortia, mostly associated with bacterial partners of the deltaproteobacterial HotSeep-1 cluster, a deeply branching phylogenetic group previously found in a butane-amended 60 °C-enrichment culture of Guaymas sediments. The closest relatives (Desulfurella spp.; Hippea maritima) are moderately thermophilic sulfur reducers. Results indicate that AOM and ANME archaea could be of biogeochemical relevance not only in cold to moderate but also in hot marine habitats

Are limnic eruptions in the CO2-CH4-rich gas reservoir of Lake Kivu (Democratic republic of the Congo and Rwanda) possible? Insights from physico-chemical and isotopic data

An overturn of Lake Kivu was seriously considered after the January 2002 Nyiragongo volcanic eruption, which erupted 20 × 106 m3 of lava from a NS-oriented fissure on the southern flank of the Congolese volcano. Part of this silica-undersaturated magma produced a lava flow that entered Lake Kivu down to a depth of 70-100 m. The possibility of a rollover comes from the fact that Lake Kivu is meromictic and below ≈250 m a CO2-CH4-rich gas reservoir is present. Thus, the riparian population (≈2,500,000 people) is endangered by a possible limnic eruption. During last 30 years several vertical profiles carried out by several researchers have evidenced a relatively pronounced vertical physico-chemical and isotopical variation. Nevertheless, saturation of CO2 and CH4 appears to be far from critical values, indicating that presently the hydrostatic pressure cannot presently be overcome. Recent studies have suggested an increase in dissolved gases (particular CH4) at depth and the uprising of the chemocline, a limnic eruption could possibly occur within 80-200 years from now. More studies are needed to follow up the lake evolution with time. Simulations will shed light on possible internal and external factors able to provoke the release a suffocating and, possibly, inflammable killer cloud. In this paper, we investigate using recent historical eruptive events of Nyiragongo volcano, we discuss the possibility that a limnic eruption may occur in a near future, although the stability of Lake Kivu is presently high: only exceptionally high magnitude events appear to be able to destabilize the 560 × 109 m3 water volume contained in its basin