Serum carbon and nitrogen stable isotopes as potential biomarkers of dietary intake and their relation with incident type 2 diabetes: the EPIC-Norfolk study.

BACKGROUND: Stable-isotope ratios of carbon (¹³C/¹²C, expressed as δ¹³C) and nitrogen (¹⁵N/¹⁴N, or δ¹⁵N) have been proposed as potential nutritional biomarkers to distinguish between meat, fish, and plant-based foods. OBJECTIVE: The objective was to investigate dietary correlates of δ¹³C and δ¹⁵N and examine the association of these biomarkers with incident type 2 diabetes in a prospective study. DESIGN: Serum δ¹³C and δ¹⁵N (‰) were measured by using isotope ratio mass spectrometry in a case-cohort study (n = 476 diabetes cases; n = 718 subcohort) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population-based cohort. We examined dietary (food-frequency questionnaire) correlates of δ¹³C and δ¹⁵N in the subcohort. HRs and 95% CIs were estimated by using Prentice-weighted Cox regression. RESULTS: Mean (±SD) δ¹³C and δ¹⁵N were -22.8 ± 0.4‰ and 10.2 ± 0.4‰, respectively, and δ¹³C (r = 0.22) and δ¹⁵N (r = 0.20) were positively correlated (P < 0.001) with fish protein intake. Animal protein was not correlated with δ¹³C but was significantly correlated with δ¹⁵N (dairy protein: r = 0.11; meat protein: r = 0.09; terrestrial animal protein: r = 0.12, P ≤ 0.013). δ¹³C was inversely associated with diabetes in adjusted analyses (HR per tertile: 0.74; 95% CI: 0.65, 0.83; P-trend < 0.001], whereas δ¹⁵N was positively associated (HR: 1.23; 95% CI: 1.09, 1.38; P-trend = 0.001). CONCLUSIONS: The isotope ratios δ¹³C and δ¹⁵N may both serve as potential biomarkers of fish protein intake, whereas only δ¹⁵N may reflect broader animal-source protein intake in a European population. The inverse association of δ¹³C but a positive association of δ¹⁵N with incident diabetes should be interpreted in the light of knowledge of dietary intake and may assist in identifying dietary components that are associated with health risks and benefits.The EPIC-Norfolk study is supported by program grants from the Medical Research Council UK and Cancer Research UK. MRC Epidemiology Unit core support is acknowledged (MC_UU_12015/1 and MC_UU_12015/5). TCO and CKK were supported by the Wellcome Trust (grant no. 074229/Z/04/Z).This version is the published accepted manuscript, distributed under a Creative Commons Attribution License 2.0. It can also be found on the publisher's website at: http://ajcn.nutrition.org/content/early/2014/07/02/ajcn.113.068577.abstrac

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

LENSOID BODIES WITHIN THE MIRADOR FORMATION, GALE CRATER - ALPHA PARTICLE X-RAY SPECTROMETER (APXS) GEOCHEMISTRY AND IMPLICATIONS FOR DEPOSITIONAL ENVIRONMENT AND TIMING

International audienceIn early 2022, Curiosity investigated a series of lenticular bodies interstratified within the Contigo member (mbr) of the Mirador formation (fm), part of the Mount Sharp Group (MtS_Grp) in Gale crater (Fig. 1), interpreted to represent localized changes in environment [1-3]. The lenses vary in size but are typically 0.5 to 1 metre thick and up to 20 metres in length. Sedimentological analysis identified commonalities between the lenses, suggesting that although they are recognized across a 50 m range in elevation (Fig. 1A), they were deposited in similar environments [1, 2]. In situ analysis with APXS was undertaken at two sites [4]. At the base of the Mirador butte, the “Prow and Panari” site (elevation -3955 m; Figs. 1, 2) encompasses “The Prow” (a ≈18 m long, ≈0.5-1 m thick lens [1]) and “Panari”, a smaller, less well-preserved lens. The “Issano” outcrop isthe highest stratigraphic lenticular body identified (elevation -3916 m; Fig. 1). The lenses exhibit markedly different chemistry to the host Contigo member and the MtS_Grp. We present APXS-derived geochemical data for the lenses. Bedrock averages include DRT (brushed) targets only and are derived using z-score analysis to identify outliers. Localized enrichments in diagenetic features (e.g., in Mg, Zn, Mn, P, S) are not reflected in these means. Mean MtS_Grp is derived from DRT targets up to the beginning of the Layered Sulfate unit (LSu) [12, 13] in the Marker Band Valley (MBV) (Fig. 1). “MtS_Grp” as used herein excludes any LSu targets

LENSOID BODIES WITHIN THE MIRADOR FORMATION, GALE CRATER - ALPHA PARTICLE X-RAY SPECTROMETER (APXS) GEOCHEMISTRY AND IMPLICATIONS FOR DEPOSITIONAL ENVIRONMENT AND TIMING

International audienceIn early 2022, Curiosity investigated a series of lenticular bodies interstratified within the Contigo member (mbr) of the Mirador formation (fm), part of the Mount Sharp Group (MtS_Grp) in Gale crater (Fig. 1), interpreted to represent localized changes in environment [1-3]. The lenses vary in size but are typically 0.5 to 1 metre thick and up to 20 metres in length. Sedimentological analysis identified commonalities between the lenses, suggesting that although they are recognized across a 50 m range in elevation (Fig. 1A), they were deposited in similar environments [1, 2]. In situ analysis with APXS was undertaken at two sites [4]. At the base of the Mirador butte, the “Prow and Panari” site (elevation -3955 m; Figs. 1, 2) encompasses “The Prow” (a ≈18 m long, ≈0.5-1 m thick lens [1]) and “Panari”, a smaller, less well-preserved lens. The “Issano” outcrop isthe highest stratigraphic lenticular body identified (elevation -3916 m; Fig. 1). The lenses exhibit markedly different chemistry to the host Contigo member and the MtS_Grp. We present APXS-derived geochemical data for the lenses. Bedrock averages include DRT (brushed) targets only and are derived using z-score analysis to identify outliers. Localized enrichments in diagenetic features (e.g., in Mg, Zn, Mn, P, S) are not reflected in these means. Mean MtS_Grp is derived from DRT targets up to the beginning of the Layered Sulfate unit (LSu) [12, 13] in the Marker Band Valley (MBV) (Fig. 1). “MtS_Grp” as used herein excludes any LSu targets

The Curiosity Rover’s Exploration of Glen Torridon, Gale crater, Mars: An Overview of the Campaign and Scientific Results

International audienceThe Mars Science Laboratory rover, Curiosity, explored the clay mineral-bearing Glen Torridon region for one martian year between January 2019 and January 2021, including a short campaign onto the Greenheugh pediment. The Glen Torridon campaign sought to characterize the geologyof the area, seek evidence of habitable environments, and document the onset of a potentially global climatic transition during the Hesperian era. Curiosity roved 5 km in total throughout Glen Torridon, from the Vera Rubin ridge to the northern margin of the Greenheugh pediment. Curiosityacquired samples from 11 drill holes during this campaign and conducted the first martian thermochemolytic-based organics detection experiment with the Sample Analysis at Mars instrument suite. The lowest elevations within Glen Torridon represent a continuation of lacustrine Murray formation deposits, but overlying widespread cross bedded sandstones indicate an interval of more energetic fluvial environments and prompted the definition of a new stratigraphic formation in the Mount Sharp group called the Carolyn Shoemaker formation. Glen Torridon hostsabundant phyllosilicates yet remains compositionally and mineralogically comparable to the rest of the Mount Sharp group. Glen Torridon samples have a great diversity and abundance of sulfurbearing organic molecules, which are consistent with the presence of ancient refractory organicmatter. The Glen Torridon region experienced heterogeneous diagenesis, with the most striking alteration occurring just below the Siccar Point unconformity at the Greenheugh pediment. Results from the pediment campaign show that the capping sandstone formed within the StimsonHesperian aeolian sand sea that experienced seasonal variations in wind direction

Wet to Dry Depositional Environments Recorded in the Clay-Sulfate Transition Region in Gale Crater, Mars: Overview and Stratigraphic Context for Curiosity's Exploration Campaign

International audienceOne of the key factors in selecting Gale crater as the landing site for the Mars Science Laboratory (MSL) mission was the ability to observeenvironmental transitions recorded in Aeolis Mons (informally known as Mt. Sharp). Orbital observations had revealed a vertical succession from strata that have abundant clay minerals to strata containing Mg sulfates [1], hypothesized to be tied to a shift from wetter to drier conditions. More recently, the Decadal Survey identified this question as central to Mars exploration: Did habitability persist through dramatic changes in the ancient climate? This work focuses on addressing the environments in which the clay-bearing and sulfatebearing units were deposited, and what that implies about the evolution of the Martian climate. Here we provide an overview of Curiosity’s exploration campaign through the clay-sulfate transition region and into the Mg sulfate-bearing unit (~Sols 3081-3755, elevation from -4072 m to -3850 m, investigated by the MSL science team from April 2021 to February 2023), and provide a summary of the sedimentological and stratigraphic context for the region

THE MARKER BAND IN GALE CRATER:: A SYNTHESIS OF ORBITAL AND GROUND OBSERVATIONS

International audienceThe “Marker Band” (previously called the Marker Bed and Marker Horizon [1-4]) in Gale crater is a distinctive indurated and dark-toned unit observed in the strata of Mount Sharp. From orbital data, the Marker Band (MB) was mapped across much of the western and southern edges of Mount Sharp, spanning over 80 km in distance and 1.6 km in elevation [4]. CRISM spectra of the MB show no hydration signatures and broad absorptions around~1 and 2 μm interpreted to be from high-Ca pyroxene [4]. Favored origins for the MB based upon orbital observations included a more indurated sulfate, a sandstone, and a volcanic ash deposit. The Curiosity rover recently reached the MB and is now collecting critical in situ measurements to test these postulated and other origins and make new discoveries at the finer mm- to cm-scale that could not be assessed from orbital data. Here we provide a summary of several of the most crucial MB observations made by the rover thus far from sols 3640-3645 and 3668-present

Metal Enrichment of Wave-Rippled Sediments on Ancient Mars

International audienceThe Curiosity rover is ascending a sedimentary-rock mountain, Mount Sharp, testing hypotheses about how and why Mars' surface dried out. Within the past year, Curiosity has investigated an apparently Mount-Sharp-spanning feature - the Marker Band, which frequently forms a topographic bench. The Marker Band is distinctive in its lateral extent, stratigraphic confinement, and nontrivial thickness. The Marker Band also shows a distinct metal-rich geochemistry unlike any other materials previously analyzed by the rover, and its lower part exhibits wave ripples extending across hundreds of meters (possibly kilometers). Thus, the Marker Band is a marker of a change in the environment within Gale crater from drier conditions that formed underlying sulfates to wetter conditions that formed wave ripples (Gupta et al. this conference). Wave ripples do not persist above the rippled Marker Band, but further clues regarding the evolution of Mars' carbon cycle and atmosphere are obtained from carbonate in drilled samples immediately above the rippled Marker Band (Tutolo et al., this conference), which is strongly elevated in δ13C (Burtt et al., this conference). APXS data for drill fines from ~1 cm depth within the rippled layers show >40 wt% FeO, ~2 wt% Zn, and >1 wt% MnO (Thompson et al., LPSC 2023); metal enrichment is also seen in ChemCam data, which also show highly variable MnO. Tentative, but reasonable extrapolation of these data to parts of the Marker Band not visited by the rover suggests an excess Fe mass of 0.2 Gton. Potential processes capable of transporting the metals include transport by chloride-rich brines, or (via interaction with CO) as metal carbonyls. Although post-lithification mechanisms for metal emplacement have not been ruled out, a possible pre-lithification mechanism involves Mn and Fe deposition in a shallow lake in oxidizing conditions. In this scenario, Fe and Mn oxide nodules form and scavenge trace metals (e.g. Zn) by adsorption. We will conclude by discussing remaining open questions about the formation and metal enrichment of the rippled Marker Band. For example, possible sources of water for metal transport include (but are not limited to) compaction water, or alternatively groundwater derived from precipitation inside the crater rim

Wet to Dry Depositional Environments Recorded in the Clay-Sulfate Transition Region in Gale Crater, Mars: Overview and Stratigraphic Context for Curiosity's Exploration Campaign

International audienceOne of the key factors in selecting Gale crater as the landing site for the Mars Science Laboratory (MSL) mission was the ability to observeenvironmental transitions recorded in Aeolis Mons (informally known as Mt. Sharp). Orbital observations had revealed a vertical succession from strata that have abundant clay minerals to strata containing Mg sulfates [1], hypothesized to be tied to a shift from wetter to drier conditions. More recently, the Decadal Survey identified this question as central to Mars exploration: Did habitability persist through dramatic changes in the ancient climate? This work focuses on addressing the environments in which the clay-bearing and sulfatebearing units were deposited, and what that implies about the evolution of the Martian climate. Here we provide an overview of Curiosity’s exploration campaign through the clay-sulfate transition region and into the Mg sulfate-bearing unit (~Sols 3081-3755, elevation from -4072 m to -3850 m, investigated by the MSL science team from April 2021 to February 2023), and provide a summary of the sedimentological and stratigraphic context for the region