The search for traces of life is one of the principal objectives of Mars exploration. Central to this objective is the concept of habitability, the set of conditions that allows the appearance of ...life and successful establishment of microorganisms in any one location. While environmental conditions may have been conducive to the appearance of life early in martian history, habitable conditions were always heterogeneous on a spatial scale and in a geological time frame. This "punctuated" scenario of habitability would have had important consequences for the evolution of martian life, as well as for the presence and preservation of traces of life at a specific landing site. We hypothesize that, given the lack of long-term, continuous habitability, if martian life developed, it was (and may still be) chemotrophic and anaerobic. Obtaining nutrition from the same kinds of sources as early terrestrial chemotrophic life and living in the same kinds of environments, the fossilized traces of the latter serve as useful proxies for understanding the potential distribution of martian chemotrophs and their fossilized traces. Thus, comparison with analog, anaerobic, volcanic terrestrial environments (Early Archean >3.5-3.33 Ga) shows that the fossil remains of chemotrophs in such environments were common, although sparsely distributed, except in the vicinity of hydrothermal activity where nutrients were readily available. Moreover, the traces of these kinds of microorganisms can be well preserved, provided that they are rapidly mineralized and that the sediments in which they occur are rapidly cemented. We evaluate the biogenicity of these signatures by comparing them to possible abiotic features. Finally, we discuss the implications of different scenarios for life on Mars for detection by in situ exploration, ranging from its non-appearance, through preserved traces of life, to the presence of living microorganisms.
Mars-Early Earth-Anaerobic chemotrophs-Biosignatures-Astrobiology missions to Mars.
Genomic loss of the mismatched human leukocyte antigen (HLA) is a recently described mechanism of leukemia immune escape and relapse after allogeneic hematopoietic stem cell transplantation (HSCT). ...Here we first evaluated its incidence, risk factors and outcome in 233 consecutive transplants from partially HLA-mismatched related and unrelated donors (MMRD and MMUD, respectively). We documented 84 relapses, 23 of which with HLA loss. All the HLA loss relapses occurred after MMRD HSCT, and 20/23 in patients with acute myeloid leukemia. Upon MMRD HSCT, HLA loss variants accounted for 33% of the relapses (23/69), occurring later than their 'classical' counterparts (median: 307 vs 88 days, P<0.0001). Active disease at HSCT increased the risk of HLA loss (hazard ratio (HR): 10.16; confidence interval (CI): 2.65-38.92; P=0.001), whereas older patient ages had a protective role (HR: 0.16; CI: 0.05-0.46; P=0.001). A weaker association with HLA loss was observed for graft T-cell dose and occurrence of chronic graft-versus-host disease. Outcome after 'classical' and HLA loss relapses was similarly poor, and second transplantation from a different donor appeared to provide a slight advantage for survival. In conclusion, HLA loss is a frequent mechanism of evasion from T-cell alloreactivity and relapse in patients with myeloid malignancies transplanted from MMRDs, warranting routine screening in this transplantation setting.
The geography of Oxia Planum Fawdon, Peter; Grindrod, Peter; Orgel, Csilla ...
Journal of maps,
12/2021, Letnik:
17, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We present the geography of Oxia Planum, the landing site for the ExoMars 2022 mission. This map provides the planetary science community with a framework to understand this, until recently, ...unexplored area. The map comprises (1) a mosaic of the panchromatic Context Camera (CTX) Digital Elevation Models (DEM) and Ortho Rectified Images (ORI) controlled to the High Resolution Stereo Camera (HRSC) multiorbit Digital Elevation Models (DEM) and (2) a mosaic of Colour and Stereo Surface Imaging System (CaSSIS) synthetic colour data products, registered to the CTX ORI mosaic. We define a grid of exploration quadrangles (quads) and an informal group of geographic regions to describe Oxia Planum. These regions bridge the scale gap between features observed on large areas (∼100s km
2
) and the local geography (10s km
2
) relevant to the Rosalind Franklin rover's operations in Oxia Planum.
Hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA) haploidentical family donors is a promising therapeutic option for high-risk hematologic malignancies. Here we ...explored in 121 patients, mostly with advanced stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of graft-versus-host disease (GvHD) to allow the infusion of unmanipulated peripheral blood stem cell (PBSC) grafts from partially HLA-matched family donors (TrRaMM study, Eudract 2007-5477-54). Conditioning regimen was based on treosulfan and fludarabine, and GvHD prophylaxis on antithymocyte globulin Fresenius (ATG-F), rituximab and oral administration of sirolimus and mycophenolate. Neutrophil and platelet engraftment occurred in median at 17 and 19 days after HSCT, respectively, and full donor chimerism was documented in patients' bone marrow since the first post-transplant evaluation. T-cell immune reconstitution was rapid, and high frequencies of circulating functional T-regulatory cells (Treg) were documented during sirolimus prophylaxis. Incidence of acute GvHD grade II-IV was 35%, and occurrence and severity correlated negatively with Treg frequency. Chronic GvHD incidence was 47%. At 3 years after HSCT, transpant-related mortality was 31%, relapse incidence 48% and overall survival 25%. In conclusion, GvHD prophylaxis with sirolimus-mycophenolate-ATG-F-rituximab promotes a rapid immune reconstitution skewed toward Tregs, allowing the infusion of unmanipulated haploidentical PBSC grafts.
Mars: new insights and unresolved questions Changela, Hitesh G.; Chatzitheodoridis, Elias; Antunes, Andre ...
International Journal of Astrobiology,
12/2021, Letnik:
20, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Abstract
Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose ...unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society. Key observations and findings include:
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high escape rates of early Mars' atmosphere, including loss of water, impact present-day habitability;
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putative fossils on Mars will likely be ambiguous biomarkers for life;
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microbial contamination resulting from human habitation is unavoidable; and
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based on Mars' current planetary protection category, robotic payload(s) should characterize the local martian environment for any life-forms prior to human habitation.
Some of the outstanding questions are:
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which interpretation of the hemispheric dichotomy of the planet is correct;
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to what degree did deep-penetrating faults transport subsurface liquids to Mars' surface;
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in what abundance are carbonates formed by atmospheric processes;
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what properties of martian meteorites could be used to constrain their source locations;
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the origin(s) of organic macromolecules;
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was/is Mars inhabited;
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how can missions designed to uncover microbial activity in the subsurface eliminate potential false positives caused by microbial contaminants from Earth;
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how can we ensure that humans and microbes form a stable and benign biosphere; and
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should humans relate to putative extraterrestrial life from a biocentric viewpoint (preservation of all biology), or anthropocentric viewpoint of expanding habitation of space?
Studies of Mars' evolution can shed light on the habitability of extrasolar planets. In addition, Mars exploration can drive future policy developments and confirm (or put into question) the feasibility and/or extent of human habitability of space.
Allogeneic HSCT (aHSCT) is the only curative treatment, reserved for IPSS-R higher risk (HR, > 3.5) MDS. Molecular data have been integrated within the recently validated IPSS-Mol score system, in ...order to better predict clinical outcome. However, IPSS-Mol is not still used to guide clinical decisions. We aim to investigate IPSS-Mol significance in a cohort of MDS patients transplanted at our center.
We retrospectively analyzed a cohort of 74 MDS patients undergoing aHSCT between 2010-2022 at our center according to IPSS-R risk score. All patients received treosulfan-based conditioning regimens and PBSC as stem cell source from matched related/unrelated or haploidentical donors. NGS testing for somatic myeloid mutations was performed retrospectively on cryopreserved marrow cells at diagnosis and MDS risk score was then re-calculated according to IPSS-Mol.
27 patients (36%) were lower risk (LR) at diagnosis and underwent aHSCT for disease progression. All the other patients were HR (IPSS-R > 3.5) and received aHSCT as upfront or consolidation treatment. At least one oncogenic mutation was found in 86.5% of cases by NGS testing. With IPSS-Mol 10 LR patients (37%) were re-stratified as HR (of note, 6/12 patients with intermediate IPSS-R ≤ 3.5), while 7 HR patients (15%) were re-stratified as LR.
aHSCT remains the only curative strategy in HR MDS. NGS testing and application of IPSS-Mol allow to better prognosticate MDS, mostly in patients with LR MDS and specifically in intermediate risk (≤3.5) group. This could help in guiding treatment and specifically optimizing the use of aHSCT in MDS.
This study deals with an aspect of blocks observed on many rocky planetary surfaces: in situ fragmentation. Using LROC/NAC images, we characterized the morphology, morphometry and abundance of ...in-situ fractured blocks observed on the rim of six large impact craters of known emplacement age on the Moon. The relative number of disrupted blocks increases with crater-retention age of surfaces on which blocks are hosted, consistent with fragmentation post-emplacement due to impacts of small meteoroids. The type of break-up morphologies we observe appears to be independent of surface exposure age of the blocks. The inferred flux and size frequency distribution of projectiles responsible for disrupting blocks is consistent with expected lunar impact fluxes. Block fragmentation due to insolation-driven thermal stresses is subordinate to impacts. The possible effects of thermal stresses are evident as meridional cracks, which have preferred orientations in a young block population (~4 Ma), and as loose material (fillet) developing on top of surviving blocks in old populations (>800 Ma).
•Using LROC/NAC images, we characterized the morphology, morphometry and abundance of in-situ fractured blocks on the Moon.•The relative number of disrupted blocks increases with the age of the surfaces on which blocks are hosted, consistent with fragmentation post-emplacement.•The inferred flux and size frequency distribution of projectiles responsible for fragmentation is consistent with meteoroid bombardment.•Block fragmentation due to insolation-driven thermal stresses is subordinate to impacts.
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