| 1. |
- Gehlen, J., et al.
(författare)
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First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B
- 2022
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Ingår i: Human Genetics and Genomics Advances. - : Elsevier BV. - 2666-2477. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes. © 2022 The Authors
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| 2. |
- Grotzinger, J.P., et al.
(författare)
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A habitable fluvio-lacustrine environment at Yellowknife Bay, Gale Crater, Mars
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6169
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Tidskriftsartikel (refereegranskat)abstract
- The Curiosity rover discovered fine-grained sedimentary rocks, which are inferred to represent an ancient lake and preserve evidence of an environment that would have been suited to support a martian biosphere founded on chemolithoautotrophy. This aqueous environment was characterized by neutral pH, low salinity, and variable redox states of both iron and sulfur species. Carbon, hydrogen, oxygen, sulfur, nitrogen, and phosphorus were measured directly as key biogenic elements; by inference, phosphorus is assumed to have been available. The environment probably had a minimum duration of hundreds to tens of thousands of years. These results highlight the biological viability of fluvial-lacustrine environments in the post-Noachian history of Mars.
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| 3. |
- Mangold, N., et al.
(författare)
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Perseverance rover reveals an ancient delta-lake system and flood deposits at Jezero crater, Mars
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6568
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Tidskriftsartikel (refereegranskat)abstract
- Observations from orbital spacecraft have shown that Jezero crater on Mars contains a prominent fan-shaped body of sedimentary rock deposited at its western margin. The Perseverance rover landed in Jezero crater in February 2021. We analyze images taken by the rover in the 3 months after landing. The fan has outcrop faces, which were invisible from orbit, that record the hydrological evolution of Jezero crater. We interpret the presence of inclined strata in these outcrops as evidence of deltas that advanced into a lake. In contrast, the uppermost fan strata are composed of boulder conglomerates, which imply deposition by episodic high-energy floods. This sedimentary succession indicates a transition from sustained hydrologic activity in a persistent lake environment to highly energetic short-duration fluvial flows.
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| 4. |
- Hankeova, S., et al.
(författare)
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Sex differences and risk factors for bleeding in Alagille syndrome
- 2022
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Ingår i: Embo Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 14:12
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Tidskriftsartikel (refereegranskat)abstract
- Spontaneous bleeds are a leading cause of death in the pediatric JAG1-related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in bleeding events in patients, whether Jag1(Ndr/Ndr) mice display bleeds or vascular defects, and whether discovered vascular pathology can be confirmed in patients non-invasively. We performed a systematic review of patients with ALGS and vascular events following PRISMA guidelines, in the context of patient sex, and found significantly more girls than boys reported with spontaneous intracranial hemorrhage. We investigated vascular development, homeostasis, and bleeding in Jag1(Ndr/Ndr) mice, using retina as a model. Jag1(Ndr/Ndr) mice displayed sporadic brain bleeds, a thin skull, tortuous blood vessels, sparse arterial smooth muscle cell coverage in multiple organs, which could be aggravated by hypertension, and sex-specific venous defects. Importantly, we demonstrated that retinographs from patients display similar characteristics with significantly increased vascular tortuosity. In conclusion, there are clinically important sex differences in vascular disease in ALGS, and retinography allows non-invasive vascular analysis in patients. Finally, Jag1(Ndr/Ndr) mice represent a new model for vascular compromise in ALGS.
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| 9. |
- Quantin-Nataf, C., et al.
(författare)
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The Complex Exhumation History of Jezero Crater Floor Unit and Its Implication for Mars Sample Return
- 2023
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Ingår i: Journal of Geophysical Research: Planets. - 2169-9097. ; 128:6
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Tidskriftsartikel (refereegranskat)abstract
- During the first year of NASA's Mars 2020 mission, Perseverance rover has investigated the dark crater floor unit of Jezero crater and four samples of this unit have been collected. The focus of this paper is to assess the potential of these samples to calibrate the crater-based Martian chronology. We first review the previous estimation of crater-based model age of this unit. Then, we investigate the impact crater density distribution across the floor unit. It reveals that the crater density is heterogeneous from areas which have been exposed to the bombardment during the last 3 Ga to areas very recently exposed to bombardment. It suggests a complex history of exposure to impact cratering. We also display evidence of several remnants of deposits on the top of the dark floor unit across Jezero below which the dark floor unit may have been buried. We propose the following scenario of burying/exhumation: the dark floor unit would have been initially buried below a unit that was a few tens of meters thick. This unit then gradually eroded away due to Aeolian processes from the northeast to the west, resulting in uneven exposure to impact bombardment over 3 Ga. A cratering model reproducing this scenario confirms the feasibility of this hypothesis. Due to the complexity of its exposure history, the Jezero dark crater floor unit will require additional detailed analysis to understand how the Mars 2020 mission samples of the crater floor can be used to inform the Martian cratering chronology.
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| 10. |
- Stack, K. M., et al.
(författare)
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Sedimentology and Stratigraphy of the Shenandoah Formation, Western Fan, Jezero Crater, Mars
- 2024
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Ingår i: Journal of Geophysical Research: Planets. - 2169-9097. ; 129:2
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Tidskriftsartikel (refereegranskat)abstract
- Sedimentary fans are key targets of exploration on Mars because they record the history of surface aqueous activity and habitability. The sedimentary fan extending from the Neretva Vallis breach of Jezero crater's western rim is one of the Mars 2020 Perseverance rover's main exploration targets. Perseverance spent ∼250 sols exploring and collecting seven rock cores from the lower ∼25 m of sedimentary rock exposed within the fan's eastern scarp, a sequence informally named the “Shenandoah” formation. This study describes the sedimentology and stratigraphy of the Shenandoah formation at two areas, “Cape Nukshak” and “Hawksbill Gap,” including a characterization, interpretation, and depositional framework for the facies that comprise it. The five main facies of the Shenandoah formation include: laminated mudstone, laminated sandstone, low-angle cross stratified sandstone, thin-bedded granule sandstone, and thick-bedded granule-pebble sandstone and conglomerate. These facies are organized into three facies associations (FA): FA1, comprised of laminated and soft sediment-deformed sandstone interbedded with broad, unconfined coarser-grained granule and pebbly sandstone intervals; FA2, comprised predominantly of laterally extensive, soft-sediment deformed laminated, sulfate-bearing mudstone with lenses of low-angle cross-stratified and scoured sandstone; and FA3, comprised of dipping planar, thin-bedded sand-gravel couplets. The depositional model favored for the Shenandoah formation involves the transition from a sand-dominated distal alluvial fan setting (FA1) to a stable, widespread saline lake (FA2), followed by the progradation of a river delta system (FA3) into the lake basin. This sequence records the initiation of a relatively long-lived, habitable lacustrine and deltaic environment within Jezero crater.
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