Bordeaux 2018: Wine, Cheese, and γδ T Cells

The 8th “International conference” was held at the University of Bordeaux, 7–10 June 2018. The lead organizer was Julie Déchanet-Merville who together with the other members of the organizing committee; Maria Mamani Matsuda, Matthias Eberl, Myriam Capone, Lionel Couzi, Hannah Kaminski, Layal Massara, Pierre Merville, Sonia Netzer, Angela Pappalardo, Charlotte Domblides, and Vincent Pitard, provided an interesting and exciting programme covering recent progress and developments in all aspects of γδ T cell research. The conference had a very good attendance with 294 delegates from 28 countries on the five continents (Figure 1). In total, 160 abstracts were submitted; resulting in 57 oral presentations and 103 poster presentations. In addition, eight “special lectures” were given after invitation. A “best poster” and “oral presentations” competition was held, covering all sessions, resulting in 10 and 5 awards, respectively (funded by AAI). Thirty-six travel awards were provided for students and post-docs by generous donations from NIH, European Federation of Immunological Societies and Gamma Delta Therapeutics Inc

Intestinal Microbiota Regulate Xenobiotic Metabolism in the Liver

BACKGROUND: The liver is the central organ for xenobiotic metabolism (XM) and is regulated by nuclear receptors such as CAR and PXR, which control the metabolism of drugs. Here we report that gut microbiota influences liver gene expression and alters xenobiotic metabolism in animals exposed to barbiturates. PRINCIPAL FINDINGS: By comparing hepatic gene expression on microarrays from germfree (GF) and conventionally-raised mice (SPF), we identified a cluster of 112 differentially expressed target genes predominantly connected to xenobiotic metabolism and pathways inhibiting RXR function. These findings were functionally validated by exposing GF and SPF mice to pentobarbital which confirmed that xenobiotic metabolism in GF mice is significantly more efficient (shorter time of anesthesia) when compared to the SPF group. CONCLUSION: Our data demonstrate that gut microbiota modulates hepatic gene expression and function by altering its xenobiotic response to drugs without direct contact with the liver

A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status

Open Access ArticleBACKGROUND: Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health. RESULTS: One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD. CONCLUSIONS: We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.European CommissionAlzheimer’s Research UKJohn and Lucille van Geest FoundationNational Institute for Health Research (NIHR)European Medical Information Framework (EMIF)Medical Research Council (MRC)Wallenberg FoundationKarolinska InstitutetSwedish Medical Research CouncilSwedish Society for Medical Research (SSMF

GDGT distributions in the East Siberian Sea: implications for organic carbon export, burial and degradation

Siberian permafrost contains a globally significant pool of organic carbon (OC) that is vulnerable to enhanced warming and subsequent release into the contemporary carbon cycle. OC release by both fluvial and coastal erosion has been reported in the region, but the behaviour of this material in the Arctic Ocean is insufficiently understood. The balance between OC deposition and degradation on the East Siberian Arctic Shelf (ESAS) influences the climate–carbon cycle feedback in this area. In this study we couple measurements of glycerol dialkyl glycerol tetraethers (GDGTs) with bulk geochemical observations to improve knowledge of the sources of OC to the ESAS, the behaviour of specific biomarkers on the shelf and the balance between delivery and removal of different carbon pools. Branched GDGT (brGDGT) concentrations were highest close to river mouths, yet low in "ice complex" permafrost deposits, supporting recent observations that brGDGTs are mostly delivered by fluvial erosion, and may be a tracer for this in complex sedimentary environments. BrGDGT concentrations and the branched and isoprenoidal tetraether (BIT) index reduced quickly offshore, demonstrating a rapid reduction in river influence. Stable carbon isotope ratios changed at a different rate to the BIT index, suggesting not only that OC on the shelf is sourced from fluvial erosion but also that erosion of coastal sediments delivers substantial quantities of OC to the Arctic Ocean. A model of OC export from fluvial, coastal and marine sources is able to recreate the biomarker and bulk observations and provide estimates for the influence of fluvial and coastal OC across the whole shelf. The model shows that coastal erosion delivers 43 % of the OC and 87 % of the mineral sediment to the ESAS, but that rivers deliver 72 % of brGDGTs, indicating that brGDGTs can be used as a proxy for river-derived sediment

Distributions of bacterial and archaeal membrane lipids in surface sediments reflect differences in input and loss of terrestrial organic carbon along a cross-shelf Arctic transect

Enhanced climate warming affecting the Arctic region could have a dramatic impact on the terrigenous organic carbon (terrOC) stored in the Eurasian permafrost and could increase the amount of OC remobilized to the Arctic shelves. An improved understanding of the fate of this remobilized soil OC is essential for better understanding of the consequences for the Arctic and global carbon cycle. In this study, glycerol dialkyl glycerol tetraethers (GDGTs) and bacteriohopanepolyols (BHPs) in surface sediments along a 500 km cross shelf transect from the mouth of the Kolyma River to the middle of the vast East Siberian Sea were analysed to assess their potential and that of the associated branched and isoprenoid tetraether (BIT) and R′soil indices for tracing terrOC in Arctic systems. Both BHP and GDGT contributions indicated the greatest contribution of terrOC close to the river mouth, while the associated indices showed declining trends in an offshore direction, supporting an increasing marine OC input and/or a decrease in terrOC. However, while the BHPs indicated a dominance of terrOC at the start of the transect, the GDGTs suggested a much larger, almost 50%, marine OC input at this point. In addition, the BIT index displayed an exponential decline, controlled mainly by a substantial contribution of marine GDGTs, while R′soil revealed a linear trend governed primarily by the removal of soil marker BHPs. These field results suggest that both biomarker approaches could be used to trace terrigenous derived OC in the Arctic environment. However, using a single proxy approach is not recommended and may lead to an under or over estimation of the relative importance of terrOC. Using a multi-proxy approach is valuable for fully understanding the fate of terrigenous derived OC along Arctic land-ocean transects

A single low-energy, iron-poor supernova as the source of metals in the star SMSS J 031300.36-670839.3

The element abundance ratios of four low-mass stars with extremely low metallicities indicate that the gas out of which the stars formed was enriched in each case by at most a few, and potentially only one low-energy, supernova. Such supernovae yield large quantities of light elements such as carbon but very little iron. The dominance of low-energy supernovae is surprising, because it has been expected that the first stars were extremely massive, and that they disintegrated in pair-instability explosions that would rapidly enrich galaxies in iron. What has remained unclear is the yield of iron from the first supernovae, because hitherto no star is unambiguously interpreted as encapsulating the yield of a single supernova. Here we report the optical spectrum of SMSS J031300.36- 670839.3, which shows no evidence of iron (with an upper limit of 10^-7.1 times solar abundance). Based on a comparison of its abundance pattern with those of models, we conclude that the star was seeded with material from a single supernova with an original mass of ~60 Mo (and that the supernova left behind a black hole). Taken together with the previously mentioned low-metallicity stars, we conclude that low-energy supernovae were common in the early Universe, and that such supernovae yield light element enrichment with insignificant iron. Reduced stellar feedback both chemically and mechanically from low-energy supernovae would have enabled first-generation stars to form over an extended period. We speculate that such stars may perhaps have had an important role in the epoch of cosmic reionization and the chemical evolution of early galaxies.Comment: 28 pages, 6 figures, Natur

Oral Health Status, Knowledge, and Practices in an Amish Population

This study was conducted in the summer of 1985 to assess the oral health status, knowledge, and practices of an Amish population in southwest Michigan. Dental caries experience, periodontal health, and oral hygiene status were recorded using decayed, missing, and filled surfaces (DMFS), periodontal index (PI), and simplified oral hygiene index (OHI-S). Data on oral health knowledge and practices were collected by interviews using a structured questionnaire. Results showed significantly lower levels of disease among Amish. DMFS scores for 5–17-year-old Amish children were almost half that of the US general population (NIDR 1979–80). PI score of all ages combined was 2.0, which was 3.6 times lower than a national sample (1971–74). Lower levels of disease in Amish could be related to their way of life and dietary patterns. A relatively higher level of unmet need for prosthodontic care, inadequate oral health knowledge, and barriers to dental care in the study population emphasize the need for dental public health and health education programs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65488/1/j.1752-7325.1988.tb03184.x.pd

Source, transport and fate of soil organic matter inferred from microbial biomarker lipids on the East Siberian Arctic Shelf

The Siberian Arctic contains a globally significant pool of organic carbon (OC) vulnerable to enhanced warming and subsequent release by both fluvial and coastal erosion processes. However, the rate of release, its behaviour in the Arctic Ocean and vulnerability to remineralisation is poorly understood. Here we combine new measurements of microbial biohopanoids including adenosylhopane, a lipid associated with soil microbial communities, with published glycerol dialkyl glycerol tetraether (GDGTs) and bulk δ13C 5 measurements to improve knowledge of the fate of OC transported to the East Siberian Arctic Shelf (ESAS). The microbial hopanoid-based soil OC proxy R'soil ranges from 0.0 to 0.8 across the ESAS, with highest values near shore and decreases offshore. Across the shelf R'soil displays a negative linear correlation with bulk δ13C measurements (r2 = −0.73, p = < 0.001). When compared to the GDGT based OC proxy, the Branched and Isoprenoid tetraether (BIT) index, a decoupled (non-linear) behaviour on the shelf was observed, particularly in the Buor-Khaya Bay where the R'soil shows limited 10 variation, whereas the BIT index shows a rapid decline moving away from the Lena River outflow channels. This reflects a balance between delivery and removal of OC from different sources. The good correlation between the hopanoid and bulk terrestrial signal suggests a broad range of hopanoid sources, both fluvial and via coastal erosion whilst GDGTs appear to be primarily sourced via fluvial transport. Analysis of ice complex deposits (ICDs) revealed an average R'soil of 0.5 for the Lena delta, equivalent to that of the Buor-Khaya Bay sediments, whilst ICDs from further East showed higher values (0.6–0.85). Al15 though R'soil correlates more closely with bulk OC than the BIT, our understanding of the endmembers of this system is clearly still incomplete with east-west variations potentially reflecting differences in environmental conditions (e.g. temperature, pH) but other physiological controls on microbial BHP production under psychrophilic conditions are as yet unknown

Trends in cancer of the cervix uteri in Sweden following cytological screening

Trends in cervical cancer incidence following the introduction of screening have mostly been studied using cross-sectional data and not analysed separately for squamous cell cancer and adenocarcinomas. Using Swedish nationwide data on incidence and mortality, we analysed trends during more than 3 decades and fitted Poisson-based age-period-cohort models, and also investigated whether screening has reduced the incidence of adenocarcinomas of the cervix. The incidence of reported cancer in situ increased rapidly during 1958–1967. Incidence rates of squamous cell cancer, fairly stable before 1968, decreased thereafter by 4–6% yearly in women aged 40–64, with a much smaller magnitude in younger and older women. An age-cohort model indicated a stable 70–75% reduction in incidence for women born 1940 and later compared with those born around 1923. The incidence of adenocarcinomas doubled during the 35-year study period. The mortality rate increased by 3.6% before 1968 and decreased by 4.0% yearly thereafter. Although a combination of organized and opportunistic screening can reduce the incidence of squamous cell cancer substantially, the incidence of adenocarcinomas appears uninfluenced by screening. © 1999 Cancer Research Campaig

Demographic routes to variability and regulation in bird populations

There is large interspecific variation in the magnitude of population fluctuations, even among closely related species. The factors generating this variation are not well understood, primarily because of the challenges of separating the relative impact of variation in population size from fluctuations in the environment. Here, we show using demographic data from 13 bird populations that magnitudes of fluctuations in population size are mainly driven by stochastic fluctuations in the environment. Regulation towards an equilibrium population size occurs through density-dependent mortality. At small population sizes, population dynamics are primarily driven by environment-driven variation in recruitment, whereas close to the carrying capacity K, variation in population growth is more strongly influenced by density-dependent mortality of both juveniles and adults. Our results provide evidence for the hypothesis proposed by Lack that population fluctuations in birds arise from temporal variation in the difference between density-independent recruitment and density-dependent mortality during the non-breeding season