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The search for biosignatures on Mars has been a high priority for astrobiology. The approach to detecting putative biosignatures has largely been focused on chemical analyses targeting predominantly extinct life. However, this approach has limited the characterization of extant life, preventing differentiation between extinct and extant biosignatures. Detecting an extant martian lifeform requires approaches focused on identification of biological features. Identifying potential features of life, such as growth or reproduction, can contribute evidence necessary to identify extant biosignatures. While an unambiguous extant biosignature might not be possible with biologically focused approaches, the combined data can provide supporting evidence to attribute a biosignature to an extinct or extant lifeform in conjunction with flight tested instrumentation. With upcoming initiatives, such as the planned Mars Sample Return campaign and the Mars Life Explorer mission concept, the incorporation of extant life specific analysis is paramount for the future of Mars exploration. [ABSTRACT FROM AUTHOR]

The Mars 2020 Perseverance Rover imaged diagenetic textural features in four separate sedimentary units in its exploration of the 25‐m‐thick Shenandoah formation at Jezero Crater, Mars, that we interpreted as probable concretions. These concretions were most abundant in the Hogwallow Flats member of the Shenandoah formation and were restricted to the light‐toned, platy, sulfur‐cemented bedrock at outcrop surfaces, whereas the finely laminated, darker toned, mottled and deformed strata lack concretions. The concretions also had a wide range of morphologies including concentric, oblate, urn, and spheroidal shaped forms that were not clustered, and ranged in size from ∼1 to 16 mm with a median of 2.65 mm. The elemental composition of the concretions compared to the bedrock had greater abundance of magnesium and calcium salts, silicates, and possibly hematite. We compared these Jezero Crater concretions to the geochemistry of concretions from previously published studies and from two new terrestrial analog sites (Gallup Formation, New Mexico and Torrey Pines, California). In addition, we measured organic carbon content of three terrestrial sedimentary analogs of increasing age that contain concretions (Torrey Pines (Pleistocene), Gallup Formation (∼89 Ma), and Moodies Group (∼3.2 Ga)). All measured concretions contained significant concentrations of organic carbon with the maximum organic carbon content (∼2 wt. % Total organic carbon) found in the Moodies Group concretions. Organic carbon abundances in terrestrial concretions was controlled more by the formation mechanism and relative timing of concretion development rather than deposit age. These findings suggested that concretions at Jezero Crater reflect local sites of enhanced biosignature preservation potential. Plain Language Summary: The Perseverance Rover discovered concretions in its exploration of the rock packages at Jezero Crater, Mars and one of the sample return cores was collected from concretion‐rich bedrock. Concretions are resistant cement in the rock that are found in many shapes (usually spherical or oblate) and range from millimeter to meter size scales on Earth; they can be formed through inorganic water‐rock reactions or facilitated by microbial metabolisms. We documented the abundance, size, composition, and shape of the concretions to understand how these features were formed. We found that the concretions are mixtures of salts, clay minerals, and iron oxides. We compared these results to terrestrial concretions with similar mineral compositions and measured the organic carbon in four terrestrial analogs. Comparisons with terrestrial concretions in this study and the literature suggested that the concretion composition in Jezero Crater could have high organic preservation potential. Thus, the concretions in Jezero Crater may retain organic carbon and other biosignatures and might therefore be considered as high priority samples of astrobiological interest out of the current sample suite for return to Earth. Key Points: Jezero Crater concretions are variably enriched in Si, Ca, and Mg salts, and Fe oxidesTerrestrial concretions of similar mineralogy analyzed in this study contain significant organic carbon phasesBased on terrestrial analogs, Jezero Crater concretions may represent sites of enhanced biosignature preservation potential [ABSTRACT FROM AUTHOR]

The proliferation of microbial carbon fixation is a key control on the evolution of the biosphere and global carbon cycle. Most records of these metabolisms in ancient rocks come from organic matter or fossils, which are not always preserved. Here, we present a potential proxy for microbial carbon fixation (autotrophy) based on the isotopic composition of carbonate minerals. Autotrophs influence carbonate chemistry in the cellular microenvironment by decreasing CO2 concentration and increasing the carbonate saturation state. This can induce rapid precipitation of carbonate minerals that are out of isotopic equilibrium with their environment. Recent work has identified disequilibrated dual clumped isotope compositions (∆47 and ∆48) in the skeletal fossils of marine calcifying organisms. Here we test whether the same is true of non‐skeletal carbonate fabrics associated with microbial autotrophs in modern and Eocene lakes. We found that microbial carbonate formed via autotrophic metabolism recorded lower ∆47 and higher ∆48 values (−∆47/+∆48) than predicted for thermodynamic equilibrium mineral formation. Our findings are supported by models of dual clumped isotope kinetics in the DIC system, and disequilibrium in the oxygen isotope system. We hypothesize that the inverse trajectory away from the equilibrium line (+∆47/−∆48) should be recorded by carbonates formed in association with alkalinizing heterotrophs, such as sulfate reducers. If so, carbonate dual clumped isotopes could be a powerful tool to identify the proliferation and rate of heterotrophic and autotrophic metabolisms in the carbonate rock record on Earth and (perhaps) other planets. Plain Language Summary: Primary producers have fueled the biosphere since the origin of life on Earth. The production of organic molecules by autotrophs is essential for the evolution of heterotrophic bacteria, and eventually fungi and animals. However, identifying where and when specific metabolisms were active in Earth history is challenging because we lack reliable biosignatures of these processes. Identifying the presence of ancient metabolic activity can provide context to how microorganisms steered global biogeochemical cycles and the carbon budget in ancient oceans, atmosphere, and on land. In this study, we present a potential fingerprint of microbial autotrophy (e.g., photosynthesis, methanogenesis) preserved in carbonate minerals in modern and ancient settings. Key Points: Microbial autotrophy imparts a dual clumped isotope and oxygen isotope disequilibrium signature on carbonate mineralsThis disequilibrium biosignature can be preserved in the rock record post‐burialDual clumped isotope signatures of microbially associated carbonates are differentiable from abiotic carbonates that formed from the same water and experienced the same burial history [ABSTRACT FROM AUTHOR]

Assessing the past habitability of Mars and searching for evidence of ancient life at Jezero crater via the Perseverance rover are the key objectives of NASA's Mars 2020 mission. Onboard the rover, PIXL (Planetary Instrument for X-ray Lithochemistry) is one of the best suited instruments to search for microbial biosignatures due to its ability to characterize chemical composition of fine scale textures in geological targets using a nondestructive technique. PIXL is also the first micro-X-ray fluorescence (XRF) spectrometer onboard a Mars rover. Here, we present guidelines for identifying and investigating a microbial biosignature in an aeolian environment using PIXL-analogous micro-XRF (μXRF) analyses. We collected samples from a modern wet aeolian environment at Padre Island, Texas, that contain buried microbial mats, and we analyzed them using μXRF techniques analogous to how PIXL is being operated on Mars. We show via μXRF technique and microscope images the geochemical and textural variations from the surface to ∼40 cm depth. Microbial mats are associated with heavy-mineral lags and show specific textural and geochemical characteristics that make them a distinct biosignature for this environment. Upon burial, they acquire a diffuse texture due to the expansion and contraction of gas-filled voids, and they present a geochemical signature rich in iron and titanium, which is due to the trapping of heavy minerals. We show that these intrinsic characteristics can be detected via μXRF analyses, and that they are distinct from buried abiotic facies such as cross-stratification and adhesion ripple laminations. We also designed and conducted an interactive survey using the Padre Island μXRF data to explore how different users chose to investigate a biosignature-bearing dataset via PIXL-like sampling strategies. We show that investigating biosignatures via PIXL-like analyses is heavily influenced by technical constraints (e.g., the XRF measurement characteristics) and by the variety of approaches chosen by different scientists. Lessons learned for accurately identifying and characterizing this biosignature in the context of rover-mission constraints include defining relative priorities among measurements, favoring a multidisciplinary approach to the decision-making process of XRF measurements selection, and considering abiotic results to support or discard a biosignature interpretation. Our results provide guidelines for PIXL analyses of potential biosignature on Mars. [ABSTRACT FROM AUTHOR]

Chemicals involved in plutonium uranium reduction extraction (PUREX) can be released from nuclear reprocessing facilities and accumulate in the environment. We exposed chemically diverse soils to a range of concentrations of key chemicals used in the PUREX process. The responses of soil microbial communities are dependent on soil type, and tributyl phosphate exposure generates the most reproducible changes in microbial communities. We reconstructed the genomes of key bacteria and find several phosphotriesterase genes found only in Rhizobiaceae. The abundance of phosphotriesterase genes is significantly higher in samples exposed to tributyl phosphate. These phosphotriesterase genes may be involved in breakdown of tributyl phosphate, and a means of accessing phosphate for these bacteria. [ABSTRACT FROM AUTHOR]

The search for biosignatures on Mars has been a high priority for astrobiology. The approach to detecting putative biosignatures has largely been focused on chemical analyses targeting predominantly extinct life. However, this approach has limited the characterization of extant life, preventing differentiation between extinct and extant biosignatures. Detecting an extant martian lifeform requires approaches focused on identification of biological features. Identifying potential features of life, such as growth or reproduction, can contribute evidence necessary to identify extant biosignatures. While an unambiguous extant biosignature might not be possible with biologically focused approaches, the combined data can provide supporting evidence to attribute a biosignature to an extinct or extant lifeform in conjunction with flight tested instrumentation. With upcoming initiatives, such as the planned Mars Sample Return campaign and the Mars Life Explorer mission concept, the incorporation of extant life specific analysis is paramount for the future of Mars exploration.

Abstract Background Mesenchymal stem/stromal cells (MSCs) can regenerate tissues through engraftment and differentiation but also via paracrine signalling via extracellular vesicles (EVs). Fetal-derived MSCs (fMSCs) have been shown, both in vitro and in animal studies, to be more efficient than adult MSC (aMSCs) in generating bone and muscle but the underlying reason for this difference has not yet been clearly elucidated. In this study, we aimed to systematically investigate the differences between fetal and adult MSCs and MSC-derived EVs at the phenotypic, RNA, and protein levels. Methods We carried out a detailed and comparative characterization of culture-expanded fetal liver derived MSCs (fMSCs) and adult bone marrow derived MSCs (aMSCs) phenotypically, and the MSCs and MSC-derived EVs were analysed using transcriptomics and proteomics approaches with RNA Sequencing and Mass Spectrometry. Results Fetal MSCs were smaller, exhibited increased proliferation and colony-forming capacity, delayed onset of senescence, and demonstrated superior osteoblast differentiation capability compared to their adult counterparts. Gene Ontology analysis revealed that fMSCs displayed upregulated gene sets such as “Positive regulation of stem cell populations”, “Maintenance of stemness” and “Muscle cell development/contraction/Myogenesis” in comparison to aMSCs. Conversely, aMSCs displayed upregulated gene sets such as “Complement cascade”, “Adipogenesis”, “Extracellular matrix glycoproteins” and “Cellular metabolism”, and on the protein level, “Epithelial cell differentiation” pathways. Signalling entropy analysis suggested that fMSCs exhibit higher signalling promiscuity and hence, higher potency than aMSCs. Gene ontology comparisons revealed that fetal MSC-derived EVs (fEVs) were enriched for “Collagen fibril organization”, “Protein folding”, and “Response to transforming growth factor beta” compared to adult MSC-derived EVs (aEVs), whereas no significant difference in protein expression in aEVs compared to fEVs could be detected. Conclusions This study provides detailed and systematic insight into the differences between fMSCs and aMSCs, and MSC-derived EVs. The key finding across phenotypic, transcriptomic and proteomic levels is that fMSCs exhibit higher potency than aMSCs, meaning they are in a more undifferentiated state. Additionally, fMSCs and fMSC-derived EVs may possess greater bone forming capacity compared to aMSCs. Therefore, using fMSCs may lead to better treatment efficacy, especially in musculoskeletal diseases.

Background: Mesenchymal stem/stromal cells (MSCs) can regenerate tissues through engraftment and differentiation but also via paracrine signalling via extracellular vesicles (EVs). Fetal-derived MSCs (fMSCs) have been shown, both in vitro and in animal studies, to be more efficient than adult MSC (aMSCs) in generating bone and muscle but the underlying reason for this difference has not yet been clearly elucidated. In this study, we aimed to systematically investigate the differences between fetal and adult MSCs and MSC-derived EVs at the phenotypic, RNA, and protein levels. Methods: We carried out a detailed and comparative characterization of culture-expanded fetal liver derived MSCs (fMSCs) and adult bone marrow derived MSCs (aMSCs) phenotypically, and the MSCs and MSC-derived EVs were analysed using transcriptomics and proteomics approaches with RNA Sequencing and Mass Spectrometry. Results: Fetal MSCs were smaller, exhibited increased proliferation and colony-forming capacity, delayed onset of senescence, and demonstrated superior osteoblast differentiation capability compared to their adult counterparts. Gene Ontology analysis revealed that fMSCs displayed upregulated gene sets such as "Positive regulation of stem cell populations", "Maintenance of stemness" and "Muscle cell development/contraction/Myogenesis" in comparison to aMSCs. Conversely, aMSCs displayed upregulated gene sets such as "Complement cascade", "Adipogenesis", "Extracellular matrix glycoproteins" and "Cellular metabolism", and on the protein level, "Epithelial cell differentiation" pathways. Signalling entropy analysis suggested that fMSCs exhibit higher signalling promiscuity and hence, higher potency than aMSCs. Gene ontology comparisons revealed that fetal MSC-derived EVs (fEVs) were enriched for "Collagen fibril organization", "Protein folding", and "Response to transforming growth factor beta" compared to adult MSC-derived EVs (aEVs), whereas no significant difference in protein expression in aEVs compared to fEVs could be detected. Conclusions: This study provides detailed and systematic insight into the differences between fMSCs and aMSCs, and MSC-derived EVs. The key finding across phenotypic, transcriptomic and proteomic levels is that fMSCs exhibit higher potency than aMSCs, meaning they are in a more undifferentiated state. Additionally, fMSCs and fMSC-derived EVs may possess greater bone forming capacity compared to aMSCs. Therefore, using fMSCs may lead to better treatment efficacy, especially in musculoskeletal diseases. [ABSTRACT FROM AUTHOR]

Agate geodes contain spheroidal patterns characterized by spectacularly coloured and circularly concentric laminations with radially aligned quartz crystals, yet the origin of these geometric patterns has remained enigmatic. Here, detailed comparisons are documented between these kinds of patterns in a selection of geodes and concretions and those produced by abiotic chemically oscillating reactions. We find strikingly comparable self-similar, fractal patterns in both natural volcanogenic geodes and sedimentary concretions as well as in these benchtop experiments. In addition, the mineralogical composition of patterns and associated organic matter point to the oxidation of organic compounds in both geodes and concretions. This process occurred during diagenetic or supergene alteration, and it is consistent with spontaneous and abiotic chemically oscillating reactions. It is concluded that the oxidation of organic acids was involved in the formation of these patterns and that these rocks indicate oxidation–reduction reactions involving organic carbon, which itself may be abiotic or biological in origin. Hence, agate geodes and concretions represent the abiotic biosignatures of possible biological origin in volcanic and sedimentary rocks. [ABSTRACT FROM AUTHOR]

Abstract The proliferation of microbial carbon fixation is a key control on the evolution of the biosphere and global carbon cycle. Most records of these metabolisms in ancient rocks come from organic matter or fossils, which are not always preserved. Here, we present a potential proxy for microbial carbon fixation (autotrophy) based on the isotopic composition of carbonate minerals. Autotrophs influence carbonate chemistry in the cellular microenvironment by decreasing CO2 concentration and increasing the carbonate saturation state. This can induce rapid precipitation of carbonate minerals that are out of isotopic equilibrium with their environment. Recent work has identified disequilibrated dual clumped isotope compositions (∆47 and ∆48) in the skeletal fossils of marine calcifying organisms. Here we test whether the same is true of non‐skeletal carbonate fabrics associated with microbial autotrophs in modern and Eocene lakes. We found that microbial carbonate formed via autotrophic metabolism recorded lower ∆47 and higher ∆48 values (−∆47/+∆48) than predicted for thermodynamic equilibrium mineral formation. Our findings are supported by models of dual clumped isotope kinetics in the DIC system, and disequilibrium in the oxygen isotope system. We hypothesize that the inverse trajectory away from the equilibrium line (+∆47/−∆48) should be recorded by carbonates formed in association with alkalinizing heterotrophs, such as sulfate reducers. If so, carbonate dual clumped isotopes could be a powerful tool to identify the proliferation and rate of heterotrophic and autotrophic metabolisms in the carbonate rock record on Earth and (perhaps) other planets.

Background: Transcriptomic profile differences between patients with bipolar disorder and healthy controls can be identified using machine learning and can provide information about the potential role of the cerebellum in the pathogenesis of bipolar disorder.With this aim, user-friendly, fully automated machine learning algorithms can achieve extremely high classification scores and disease-related predictive biosignature identification, in short time frames and scaled down to small datasets. Method: A fully automated machine learning platform, based on the most suitable algorithm selection and relevant set of hyper-parameter values, was applied on a preprocessed transcriptomics dataset, in order to produce a model for biosignature selection and to classify subjects into groups of patients and controls. The parent GEO datasets were originally produced from the cerebellar and parietal lobe tissue of deceased bipolar patients and healthy controls, using Affymetrix Human Gene 1.0 ST Array. Results: Patients and controls were classified into two separate groups, with no close-to-the-boundary cases, and this classification was based on the cerebellar transcriptomic biosignature of 25 features (genes), with Area Under Curve 0.929 and Average Precision 0.955. The biosignature includes both genes connected before to bipolar disorder, depression, psychosis or epilepsy, as well as genes not linked before with any psychiatric disease. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed participation of 4 identified features in 6 pathways which have also been associated with bipolar disorder. Conclusion: Automated machine learning (AutoML) managed to identify accurately 25 genes that can jointly – in a multivariate–fashion - separate bipolar patients from healthy controls with high predictive power. The discovered features lead to new biological insights. Machine Learning (ML) analysis considers the features in combination (in contrast to standard differential expression analysis), removing both irrelevant as well as redundant markers, and thus, focusing to biological interpretation.

For billions of years, life has continuously adapted to dynamic physical conditions near the Earth's surface. Fossils and other preserved biosignatures in the paleontological record are the most direct evidence for reconstructing the broad historical contours of this adaptive interplay. However, biosignatures dating to Earth's earliest history are exceedingly rare. Here, we combine phylogenetic inference of primordial rhodopsin proteins with modeled spectral features of the Precambrian Earth environment to reconstruct the paleobiological history of this essential family of photoactive transmembrane proteins. Our results suggest that ancestral microbial rhodopsins likely acted as light-driven proton pumps and were spectrally tuned toward the absorption of green light, which would have enabled their hosts to occupy depths in a water column or biofilm where UV wavelengths were attenuated. Subsequent diversification of rhodopsin functions and peak absorption frequencies was enabled by the expansion of surface ecological niches induced by the accumulation of atmospheric oxygen. Inferred ancestors retain distinct associations between extant functions and peak absorption frequencies. Our findings suggest that novel information encoded by biomolecules can be used as "paleosensors" for conditions of ancient, inhabited niches of host organisms not represented elsewhere in the paleontological record. The coupling of functional diversification and spectral tuning of this taxonomically diverse protein family underscores the utility of rhodopsins as universal testbeds for inferring remotely detectable biosignatures on inhabited planetary bodies.

The concept of a biosignature is widely used in astrobiology to suggest a link between some observation and a biological cause, given some context. The term itself has been defined and used in several ways in different parts of the scientific community involved in the search for past or present life on Earth and beyond. With the ongoing acceleration in the search for life in distant time and/or deep space, there is a need for clarity and accuracy in the formulation and reporting of claims. Here, we critically review the biosignature concept(s) and the associated nomenclature in light of several problems and ambiguities emphasized by recent works. One worry is that these terms and concepts may imply greater certainty than is usually justified by a rational interpretation of the data. A related worry is that terms such as "biosignature" may be inherently misleading, for example, because the divide between life and non-life—and their observable effects—is fuzzy. Another worry is that different parts of the multidisciplinary community may use non-equivalent or conflicting definitions and conceptions, leading to avoidable confusion. This review leads us to identify a number of pitfalls and to suggest how they can be circumvented. In general, we conclude that astrobiologists should exercise particular caution in deciding whether and how to use the concept of biosignature when thinking and communicating about habitability or life. Concepts and terms should be selected carefully and defined explicitly where appropriate. This would improve clarity and accuracy in the formulation of claims and subsequent technical and public communication about some of the most profound and important questions in science and society. With this objective in mind, we provide a checklist of questions that scientists and other interested parties should ask when assessing any reported detection of a "biosignature" to better understand exactly what is being claimed. [ABSTRACT FROM AUTHOR]

Here I pursue a deconstructive reading of astrobiology, the emerging science dedicated to a double quest: solving the mystery of life's origin and discovering life beyond Earth. Astrobiology, I argue, is organized as a response to the aporetic formulation assumed by the origin of life in modern molecular biology, where (as Derrida's argues in Life Death) it becomes the origin of textuality. Because all Earth life shares a single genetic code, astrobiologists are seeking a second; hoping that a sort of multi-planetary comparative genomics may reveal the secret to life's origin. But the aporia repeats in the figure of the biosignature, the trace of life. [ABSTRACT FROM AUTHOR]

Evidence of liquid water is a primary indicator of habitability on the icy moons in our outer solar system as well as on terrestrial planets such as Mars. If liquid water-containing environments host life, some of its organic remains can be fossilized and preserved as organic biosignatures. However, inorganic materials may also be present and water-assisted organic–inorganic reactions can transform the organic architecture of biological remains. Our understanding of the fate of these organic remains can be assisted by experimental simulations that monitor the chemical changes that occur in microbial organic matter due to the presence of water and minerals. We performed hydrothermal experiments at temperatures between 100°C and 300°C involving lipid-rich microbes and natural serpentinite mineral mixtures generated by the subaqueous hydrothermal alteration of ultramafic rock. The products reveal what the signals of life may look like when subjected to water–organic–inorganic reactions. Straight- and branched-chain lipids in unaltered samples are joined by cyclization and aromatization products in hydrothermally altered samples. Hydrothermal reactions produce distinct products that are not present in the starting materials, including small, single-ring, heteroatomic, and aromatic compounds such as indoles and phenols. Hydrothermal reactions in the presence of serpentinite minerals lead to significant reduction of these organic structures and their replacement by diketopiperazines (DKPs) and dihydropyrazines (DHPs), which may be compounds that are distinct to organic–inorganic reactions. Given that the precursors of DKPs and DHPs are normally lost during early diagenesis, the presence of these compounds can be an indicator of coexisting recent life and hydrothermal processing in the presence of minerals. However, laboratory experiments reveal that the formation and preservation of these compounds can only occur within a distinct temperature window. Our findings are relevant to life detection missions that aim to access hydrothermal and serpentinizing environments in the subsurfaces of icy moons and Mars. [ABSTRACT FROM AUTHOR]

Discrepancies have emerged concerning the application of sulfur stable isotope ratios as a biosignature in impact crater paleolakes. The first in situ δ34S data from Mars at Gale crater display a ∼75‰ range that has been attributed to an abiotic mechanism. Yet biogeochemical studies of ancient environments on Earth generally interpret δ34S fractionations >21‰ as indicative of a biological origin, and studies of δ34S at analog impact crater lakes on Earth have followed the same approach. We performed analyses (including δ34S, total organic carbon wt%, and scanning electron microscope imaging) on multiple lithologies from the Nördlinger Ries impact crater, focusing on hydrothermally altered impact breccias and associated sedimentary lake-fill sequences to determine whether the δ34S properties define a biosignature. The differences in δ34S between the host lithologies may have resulted from thermochemical sulfate reduction, microbial sulfate reduction, hydrothermal equilibrium fractionation, or any combination thereof. Despite abundant samples and instrumental precision currently exclusive to Earth-bound analyses, assertions of biogenicity from δ34S variations >21‰ at the Miocene Ries impact crater are tenuous. This discourages the use of δ34S as a biosignature in similar environments without independent checks that include the full geologic, biogeochemical, and textural context, as well as a comprehensive acknowledgment of alternative hypotheses. [ABSTRACT FROM AUTHOR]

Abstract Background To improve tuberculosis (TB) diagnosis, the World Health Organisation (WHO) has called for a non-sputum based triage test to focus TB testing on people with a high likelihood of having active pulmonary tuberculosis (TB). Various host or pathogen biomarker-based testing devices are in design stage and require validity assessment. Host biomarkers have shown promise to accurately rule out active TB, but further research is required to determine generalisability. The TriageTB diagnostic test study aims to assess the accuracy of diagnostic test candidates, as well as field-test, finalise the design and biomarker signature, and validate a point-of-care multi-biomarker test (MBT). Methods This observational diagnostic study will evaluate sensitivity and specificity of biomarker-based diagnostic candidates including the MBT and Xpert® TB Fingerstick cartridge compared with a gold-standard composite TB outcome classification defined by symptoms, sputum GeneXpert® Ultra, smear and culture, radiological features, response to TB therapy and presence of an alternative diagnosis. The study will be conducted in research sites in South Africa, Uganda, The Gambia and Vietnam which all have high TB prevalence. The two-phase design allows for finalisation of the MBT in Phase 1 in which candidate host proteins will be evaluated on stored serum from Asia, South Africa and South America and on fingerstick blood from 50 newly recruited participants per site. The MBT test will then be locked down and validated in Phase 2 on 250 participants per site. Discussion By targeting confirmatory TB testing to those with a positive triage test, 75% of negative GXPU may be avoided, thereby reducing diagnostic costs and patient losses during the care cascade. This study builds on previous biomarker research and aims to identify a point-of-care test meeting or exceeding the minimum World Health Organisation target product profile of a 90% sensitivity and 70% specificity. Streamlining TB testing by identifying individuals with a high likelihood of TB should improve TB resources use and, in so doing, improve TB care. Trial registration NCT04232618 (clinicaltrials.gov) Date of registration: 16 January 2020.

Recent advances in automated microscopy and image analysis enables quantitative profiling of cellular phenotypes (Cell Painting). It paves the way for studying the broad effects of chemical perturbations on biological systems at large scale during lead optimization. Comparison of perturbation biosignatures with biosignatures of annotated compounds can inform on both on- and off-target effects. When building databases with phenotypic profiles of thousands of compounds, it is vital to control the quality of Cell Painting assays over time. A tool for this to our knowledge does not yet exist within the imaging community. In this paper, we introduce an automated tool to assess the quality of Cell Painting assays by quantifying the reproducibility of biosignatures of annotated reference compounds. The tool learns the biosignature of those treatments from a historical dataset, and subsequently, it builds a two-dimensional probabilistic quality control (QC) limit. The limit will then be used to detect aberrations in new Cell Painting experiments. The tool is illustrated using simulated data and further demonstrated on Cell Painting data of the A549 cell line. In general, the tool provides a sensitive, detailed and easy-to-interpret mechanism to validate the quality of Cell Painting assays.

Background: To improve tuberculosis (TB) diagnosis, the World Health Organisation (WHO) has called for a non-sputum based triage test to focus TB testing on people with a high likelihood of having active pulmonary tuberculosis (TB). Various host or pathogen biomarker-based testing devices are in design stage and require validity assessment. Host biomarkers have shown promise to accurately rule out active TB, but further research is required to determine generalisability. The TriageTB diagnostic test study aims to assess the accuracy of diagnostic test candidates, as well as field-test, finalise the design and biomarker signature, and validate a point-of-care multi-biomarker test (MBT). Methods: This observational diagnostic study will evaluate sensitivity and specificity of biomarker-based diagnostic candidates including the MBT and Xpert® TB Fingerstick cartridge compared with a gold-standard composite TB outcome classification defined by symptoms, sputum GeneXpert® Ultra, smear and culture, radiological features, response to TB therapy and presence of an alternative diagnosis. The study will be conducted in research sites in South Africa, Uganda, The Gambia and Vietnam which all have high TB prevalence. The two-phase design allows for finalisation of the MBT in Phase 1 in which candidate host proteins will be evaluated on stored serum from Asia, South Africa and South America and on fingerstick blood from 50 newly recruited participants per site. The MBT test will then be locked down and validated in Phase 2 on 250 participants per site. Discussion: By targeting confirmatory TB testing to those with a positive triage test, 75% of negative GXPU may be avoided, thereby reducing diagnostic costs and patient losses during the care cascade. This study builds on previous biomarker research and aims to identify a point-of-care test meeting or exceeding the minimum World Health Organisation target product profile of a 90% sensitivity and 70% specificity. Streamlining TB testing by identifying individuals with a high likelihood of TB should improve TB resources use and, in so doing, improve TB care. Trial registration: NCT04232618 (clinicaltrials.gov) Date of registration: 16 January 2020. [ABSTRACT FROM AUTHOR]

Motility is a great biosignature and its pattern is characteristic for specific microbes. However, motion does also occur within the cell by the myriads of ongoing processes within the cell and the exchange of gases and nutrients with the outside environment. Here, we propose that the sum of these processes in a microbial cell is equivalent to a pulse in complex organisms and suggest a first approach to measure the "living pulse" in microorganisms. We emphasize that if a "living pulse" can be shown to exist, it would have far-reaching applications, such as for finding life in extreme environments on Earth and in extraterrestrial locations, as well as making sure that life is not present where it should not be, such as during medical procedures and in the food processing industry. [ABSTRACT FROM AUTHOR]

Agate geodes contain spheroidal patterns characterized by spectacularly coloured and circularly concentric laminations with radially aligned quartz crystals, yet the origin of these geometric patterns has remained enigmatic. Here, detailed comparisons are documented between these kinds of patterns in a selection of geodes and concretions and those produced by abiotic chemically oscillating reactions. We find strikingly comparable self-similar, fractal patterns in both natural volcanogenic geodes and sedimentary concretions as well as in these benchtop experiments. In addition, the mineralogical composition of patterns and associated organic matter point to the oxidation of organic compounds in both geodes and concretions. This process occurred during diagenetic or supergene alteration, and it is consistent with spontaneous and abiotic chemically oscillating reactions. It is concluded that the oxidation of organic acids was involved in the formation of these patterns and that these rocks indicate oxidation–reduction reactions involving organic carbon, which itself may be abiotic or biological in origin. Hence, agate geodes and concretions represent the abiotic biosignatures of possible biological origin in volcanic and sedimentary rocks.

Oxalate serves various functions in the biological processes of plants, fungi, bacteria, and animals. It occurs naturally in the minerals weddellite and whewellite (calcium oxalates) or as oxalic acid. The environmental accumulation of oxalate is disproportionately low compared to the prevalence of highly productive oxalogens, namely plants. It is hypothesized that oxalotrophic microbes limit oxalate accumulation by degrading oxalate minerals to carbonates via an underexplored biogeochemical cycle known as the oxalate-carbonate pathway (OCP). Neither the diversity nor the ecology of oxalotrophic bacteria is fully understood. This research investigated the phylogenetic relationships of the bacterial genes oxc, frc, oxdC, and oxlT, which encode key enzymes for oxalotrophy, using bioinformatic approaches and publicly available omics datasets. Phylogenetic trees of oxc and oxdC genes demonstrated grouping by both source environment and taxonomy. All four trees included genes from metagenome-assembled genomes (MAGs) that contained novel lineages and environments for oxalotrophs. In particular, sequences of each gene were recovered from marine environments. These results were supported with marine transcriptome sequences and description of key amino acid residue conservation. Additionally, we investigated the theoretical energy yield from oxalotrophy across marine-relevant pressure and temperature conditions and found similar standard state Gibbs free energy to "low energy" marine sediment metabolisms, such as anaerobic oxidation of methane coupled to sulfate reduction. These findings suggest further need to understand the role of bacterial oxalotrophy in the OCP, particularly in marine environments, and its contribution to global carbon cycling. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis without nasal polyps (CRSsNP) represents a phenotype of CRS, whose immunological mechanisms are still unclear. So far there are neither suitable biomarkers to determine the course of the disease nor an individual therapy. Objective: The purpose of this study was to characterize the CRSsNP endotype by identifying and validating non-invasive proteomic biomarkers. Methods: A highly-multiplexed proteomic array consisting of antibodies against 2000 proteins was used to identify proteins that are differentially expressed in the nasal mucus of the CRSsNP and control groups (n = 7 per group). The proteins identified to be most differentially expressed were validated in matched nasal mucus samples using western blots and enzyme-linked immunosorbent assay (ELISA). Validation was also done in a second cohort using western blots (CRSsNP n = 25, control n = 23) and ELISA (n = 30 per group). Additionally, immunohistochemistry in CRSsNP and control tissue samples was performed to characterize the selected proteins further. Results: Out of the 2000 proteins examined, 7 from the most differentially expressed proteins were chosen to be validated. The validation results showed that 4 proteins were significantly upregulated in CRSsNP mucus, including macrophage inflammatory protein-1beta (MIP-1β), resistin, high mobility group box 1 (HMGB1), and forkhead box protein 3 (FOXP3). Cartilage acidic protein 1 (CRTAC1) was not significantly upregulated. Two proteins were significantly downregulated including scavenger receptor class F member 2 (SCARF2) and P-selectin. All proteins selected are mainly associated with inflammation, cell proliferation/differentiation, apoptosis and cell–cell or cell–matrix interaction. Conclusion: Proteomic analysis of CRSsNP and control mucus has confirmed known and revealed novel disease-associated proteins that could potentially serve as a new biosignature for CRSsNP. Analysis of the associated pathways will specify endotypes of CRSsNP and will lead to an improved understanding of the pathophysiology of CRSsNP. Furthermore, our data contribute to the development of a reproducible, non-invasive, and quantitative "liquid biopsy" for rhinosinusitis. [ABSTRACT FROM AUTHOR]

The microbial dolomite model has been used to interpret the origin of sedimentary dolomite. In this model, the formation of low-temperature protodolomite, an important precursor to sedimentary dolomite, can be facilitated either by actively metabolizing cells of anaerobic microbes and aerobic halophilic archaea or by their inactive biomass. Aerobic halophilic bacteria are widely distributed in (proto-)dolomite-depositing evaporitic environments and their biomass might serve as a template for the crystallization of protodolomite. To test this hypothesis, carbonation experiments were conducted using dead biomass of an aerobic halophilic bacterium (Exiguobacterium sp. strain JBHLT-3). Our results show that dead biomass of JBHLT-3 can accelerate Mg2+ uptake in carbonate mineral precipitates. In addition, the amount of Mg incorporated into Ca-Mg carbonates is proportional to the concentration of biomass. High Mg-calcite is produced with 0.25 or 0.5 g/L biomass, whereas protodolomite forms with 1 g/L biomass. This is confirmed by the main Raman peak of Ca-Mg carbonates, which shifts towards higher wavenumbers with increased Mg substitution. Microbial cells and their imprints are preserved on the surface of high Mg-calcite and protodolomite. Hence, this study furthers our understanding of the dolomitization within buried and dead microbial mats, which provides useful insights into the origin of ancient dolomite. [ABSTRACT FROM AUTHOR]

Recent progress in extremophile biology, exploration of planetary bodies in the solar system, and the detection and characterization of extrasolar planets are leading to new insights in the field of astrobiology and possible distribution of life in the universe. Among the many extremophiles on Earth, the halophilic Archaea (Haloarchaea) are especially attractive models for astrobiology, being evolutionarily ancient and physiologically versatile, potentially surviving in a variety of planetary environments and with relevance for in situ life detection. Haloarchaea are polyextremophilic with tolerance of saturating salinity, anaerobic conditions, high levels of ultraviolet and ionizing radiation, subzero temperatures, desiccation, and toxic ions. Haloarchaea survive launches into Earth's stratosphere encountering conditions similar to those found on the surface of Mars. Studies of their unique proteins are revealing mechanisms permitting activity and function in high ionic strength, perchlorates, and subzero temperatures. Haloarchaea also produce spectacular blooms visible from space due to synthesis of red-orange isoprenoid carotenoids used for photoprotection and photorepair processes and purple retinal chromoproteins for phototrophy and phototaxis. Remote sensing using visible and infrared spectroscopy has shown that haloarchaeal pigments exhibit both a discernable peak of absorption and a reflective "green edge". Since the pigments produce remotely detectable features, they may influence the spectrum from an inhabited exoplanet imaged by a future large space-based telescope. In this review, we focus primarily on studies of two Haloarchaea, Halobacterium sp. NRC-1 and Halorubrum lacusprofundi.

For decades, the search for potential signs of Martian life has attracted strong international interest and has led to significant planning and scientific implementation. Clearly, in order to detect potential life signals beyond Earth, fundamental questions, such as how to define such terms as “life” and “biosignature”, have been given considerable attention. Due to the high costs of direct exploration of Mars, Mars-like regions on Earth have been invaluable targets for astrobiological research, places where scientists could practice the search for “biosignatures” and refine ways to detect them. This review summarizes scientific instrumental techniques that have resulted from this work. Instruments must necessarily be our “eyes” and “hands” as we attempt to identify and quantify biosignatures on Mars. Scientific devices that can be applied in astrobiology include mass spectrometers and electromagnetic-spectrum-based spectrometers, redox potential indicators, circular dichroism polarimeters, in situ nucleic acid sequencers, life isolation/cultivation systems, and imagers. These devices and how to interpret the data they collect have been tested in Mars-analog extreme environments on Earth to validate their practicality on Mars. To anticipate the challenges of instrumental detection of biosignatures through the full evolutionary history of Mars, Terrestrial Mars analogs are divided into four major categories according to their similarities to different Martian geological periods (the Early−Middle Noachian Period, the Late Noachian−Early Hesperian Period, the Late Hesperian−Early Amazonian Period, and the Middle−Late Amazonian Period). Future missions are suggested that would focus more intensively on Mars’ Southern Hemisphere, once landing issues there are solved by advances in spacecraft engineering, since exploration of these early terrains will permit investigations covering a wider continuum of the shifting habitability of Mars through its geological history. Finally, this paper reviews practical applications of the range of scientific instruments listed above, based on the four categories of Mars analogs here on Earth. We review the selection of instruments suitable for autonomous robotic rover tests in these Mars analogs. From considerations of engineering efficiency, a Mars rover ought to be equipped with as few instrument assemblies as possible. Therefore, once candidate landing regions on Mars are defined, portable suites of instruments should be smartly devised on the basis of the known geological, geochemical, geomorphological, and chronological characteristics of each Martian landing region. Of course, if Mars sample-return missions are successful, such samples will allow experiments in laboratories on Earth that can be far more comprehensive and affordable than is likely to be practicable on Mars. To exclude false positive and false negative conclusions in the search for extraterrestrial life, multiple diverse and complementary analytical techniques must be combined, replicated, and carefully interpreted. The question of whether signatures of life can be detected on Mars is of the greatest importance. Answering that question is extremely challenging but appears to have become manageable.

Ketamine is a NMDA receptor antagonist that has a rapid acting antidepressant effect with high efficacy in treatment-resistant patients. Ketamine is a beneficial antidepressant for many individuals with depression, but not all of the patients respond, and some even exhibit symptom deterioration. The discovery of repeatable and mechanistically relevant biomarkers would address a major gap in treatment response prediction. Numerous potential peripheral biomarkers have been reported, but their current utility is unclear. We conducted an umbrella review to evaluate the biomarkers of ketamine's antidepressant effect in individuals with depression. PubMed and copus were searched using terms appropriate to each area of research, from their inception until July 2022. Five systematic reviews and meta analyses including 108 studies with 4912 participants were included. Blood-based and neuroimaging biomarkers were investigated. The results of this review indicate that ketamine can produce an anti-inflammatory effect and decrease at least one inflammatory marker following administration. Data from neuroimaging studies demonstrated that the cingulate cortex is the key locus of ketamine's action. The majority of the blood-based, neuroimaging, and neurophysiological investigations reviewed herein indicate ketamine induced normalization of major depressive disorder pathogenesis via synaptic plasticity and functional connectivity. Currently, no biomarker/biosignature is sufficiently validated for clinical utility, but several are promising. Now that ketamine is more widely available, biomarker discovery and replication should be attempted in larger, real-world populations. • Five systematic reviews and meta analyses including 108 studies with 4912 participants were included. • Ketamine can induce anti inflammatory effect and decrease at least one inflammatory marker. • IL-6, TNF-α and CRP were the most studied inflammatory biomarkers in included studies. • The cingulate cortex is the key locus of ketamine's action. [ABSTRACT FROM AUTHOR]

Water present on early Mars is often assumed to have been habitable. In this study, experiments were performed to investigate the habitability of well-defined putative martian fluids and to identify the accompanying potential formation of biosignatures. Simulated martian environments were developed by combining martian fluid and regolith simulants based on the chemistry of the Rocknest sand shadow at Gale Crater. The simulated chemical environment was inoculated with terrestrial anoxic sediment from the Pyefleet mudflats (United Kingdom). These enrichments were cultured for 28 days and subsequently subcultured seven times to ensure that the microbial community was solely grown on the defined, simulated chemistry. The impact of the simulated chemistries on the microbial community was assessed by cell counts and sequencing of 16S rRNA gene profiles. Associated changes to the fluid and precipitate chemistries were established by using ICP-OES, IC, FTIR, and NIR. The fluids were confirmed as habitable, with the enriched microbial community showing a reduction in abundance and diversity over multiple subcultures relating to the selection of specific metabolic groups. The final community comprised sulfate-reducing, acetogenic, and other anaerobic and fermentative bacteria. Geochemical characterization and modeling of the simulant and fluid chemistries identified clear differences between the biotic and abiotic experiments. These differences included the elimination of sulfur owing to the presence of sulfate-reducing bacteria and more general changes in pH associated with actively respiring cells that impacted the mineral assemblages formed. This study confirmed that a system simulating the fluid chemistry of Gale Crater could support a microbial community and that variation in chemistries under biotic and abiotic conditions can be used to inform future life-detection missions. [ABSTRACT FROM AUTHOR]

The record of life during the Proterozoic is preserved by several different lithologies, but two in particular are linked both spatially and temporally: chert and carbonate. These lithologies capture a snapshot of dominantly peritidal environments during the Proterozoic. Early diagenetic chert preserves some of the most exceptional Proterozoic biosignatures in the form of microbial body fossils and mat textures. This fossiliferous and kerogenous chert formed in shallow marine environments, where chert nodules, layers, and lenses are often surrounded by and encased within carbonate deposits that themselves often contain kerogen and evidence of former microbial mats. Here, we review the record of biosignatures preserved in peritidal Proterozoic chert and chert‐hosting carbonate and discuss this record in the context of experimental and environmental studies that have begun to shed light on the roles that microbes and organic compounds may have played in the formation of these deposits. Insights gained from these studies suggest temporal trends in microbial‐environmental interactions and place new constraints on past environmental conditions, such as the concentration of silica in Proterozoic seawater, interactions among organic compounds and cations in seawater, and the influence of microbial physiology and biochemistry on selective preservation by silicification. [ABSTRACT FROM AUTHOR]

Oxalate serves various functions in the biological processes of plants, fungi, bacteria, and animals. It occurs naturally in the minerals weddellite and whewellite (calcium oxalates) or as oxalic acid. The environmental accumulation of oxalate is disproportionately low compared to the prevalence of highly productive oxalogens, namely plants. It is hypothesized that oxalotrophic microbes limit oxalate accumulation by degrading oxalate minerals to carbonates via an under-explored biogeochemical cycle known as the oxalate-carbonate pathway (OCP). Neither the diversity nor the ecology of oxalotrophic bacteria is fully understood. This research investigated the phylogenetic relationships of the bacterial genes oxc, frc, oxdC, and oxlT, which encode key enzymes for oxalotrophy, using bioinformatic approaches and publicly available omics datasets. Phylogenetic trees of oxc and oxdC genes demonstrated grouping by both source environment and taxonomy. All four trees included genes from metagenome-assembled genomes (MAGs) that contained novel lineages and environments for oxalotrophs. In particular, sequences of each gene were recovered from marine environments. These results were supported with marine transcriptome sequences and description of key amino acid residue conservation. Additionally, we investigated the theoretical energy yield from oxalotrophy across marine-relevant pressure and temperature conditions and found similar standard state Gibbs free energy to “low energy” marine sediment metabolisms, such as anaerobic oxidation of methane coupled to sulfate reduction. These findings suggest further need to understand the role of bacterial oxalotrophy in the OCP, particularly in marine environments, and its contribution to global carbon cycling.

Background: Host innate immune cells have been identified as key players in the early eradication of Mycobacterium tuberculosis and in the maintenance of an anti-mycobacterial immune memory, which we and others have shown are induced through epigenetic reprogramming. Studies on human tuberculosis immunity are dominated by those using peripheral blood as surrogate markers for immunity. We aimed to investigate DNA methylation patterns in immune cells of the lung compartment by obtaining induced sputum from M. tuberculosis- exposed subjects including symptom-free subjects testing positively and negatively for latent tuberculosis as well as patients diagnosed with active tuberculosis. Alveolar macrophages and alveolar T cells were isolated from the collected sputum and DNA methylome analyses performed (Illumina Infinium Human Methylation 450 k). Results: Multidimensional scaling analysis revealed that DNA methylomes of cells from the tuberculosis-exposed subjects and controls appeared as separate clusters. The numerous genes that were differentially methylated between the groups were functionally connected and overlapped with previous findings of trained immunity and tuberculosis. In addition, analysis of the interferon-gamma release assay (IGRA) status of the subjects demonstrated that the IGRA status was reflected in the DNA methylome by a unique signature. Conclusions: This pilot study suggests that M. tuberculosis induces epigenetic reprogramming in immune cells of the lung compartment, reflected as a specific DNA methylation pattern. The DNA methylation signature emerging from the comparison of IGRA-negative and IGRA-positive subjects revealed a spectrum of signature strength with the TB patients grouping together at one end of the spectrum, both in alveolar macrophages and T cells. DNA methylation-based biosignatures could be considered for further development towards a clinically useful tool for determining tuberculosis infection status and the level of tuberculosis exposure. [ABSTRACT FROM AUTHOR]

Post-acute COVID-19 syndrome (PACS) has been defined as symptoms persisting after clearance of a COVID-19 infection. We have previously demonstrated that alterations in DNA methylation (DNAm) status persist in individuals who recovered from a COVID-19 infection, but it is currently unknown if PACS is associated with epigenetic changes. We compared DNAm patterns in patients with PACS with those in controls and in healthy COVID-19 convalescents and found a unique DNAm signature in PACS patients. This signature unravelled modified pathways that regulate angiotensin II and muscarinic receptor signalling and protein–protein interaction networks that have bearings on vesicle formation and mitochondrial function. [ABSTRACT FROM AUTHOR]

Anthraquinones are a family of natural products with useful bioactivity and optical properties. An anthraquinone called parietin is produced by extremophiles to protect against solar ultraviolet B radiation, so it is a potential biosignature in astrobiology. Raman spectroscopy, which is now used in space environments, can detect molecules such as parietin based on molecular vibrations. In this study, we show that time-dependent density functional theory (TDDFT) can accurately calculate the Raman spectra of three dihydroxyanthraquinones: parietin, emodin, and chrysophanol. By comparing calculated spectra to measured Raman spectra from purified powders, 10 vibrational modes are identified. The detailed molecular motions of these fused ring vibrations are described, and vibrations modes that are common to all three molecules are highlighted. In addition to powder spectra, Raman measurements from the thallus of Xanthoria parietina, a lichen that produces parietin, are reported, with excellent agreement to both the parietin powder and calculated Raman spectra. These results show that TDDFT calculations could make significant contributions to spectral analysis in the search for biotic organic materials beyond Earth. [ABSTRACT FROM AUTHOR]

The current strategy for detecting evidence of ancient life on Mars—a primary goal of NASA's ongoing Mars 2020 mission—is based largely on knowledge of Precambrian life and of its preservation in Earth's early rock record. The fossil record of primitive microorganisms consists mainly of stromatolites and other microbially influenced sedimentary structures, which occasionally preserve microfossils or other geochemical traces of life. Raman spectroscopy is an invaluable tool for identifying such signs of life and is routinely performed on Precambrian microfossils to help establish their organic composition, degree of thermal maturity, and biogenicity. The Mars 2020 rover, Perseverance, is equipped with a deep-ultraviolet (UV) Raman spectrometer as part of the SHERLOC (Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals) instrument, which will be used in part to characterize the preservation of organic matter in the ancient sedimentary rocks of Jezero crater and therein search for possible biosignatures. To determine the deep-UV Raman spectra characteristic of ancient microbial fossils, this study analyzes individual microfossils from 14 Precambrian cherts using deep-UV (244 nm) Raman spectroscopy. Spectra obtained were measured and calibrated relative to a graphitic standard and categorized according to the morphology and depositional environment of the fossil analyzed and its Raman-indicated thermal maturity. All acquired spectra of the fossil kerogens include a considerably Raman-enhanced and prominent first-order Raman G-band (∼1600 cm−1), whereas its commonly associated D-band (∼1350 cm−1) is restricted to specimens of lower thermal maturity (below greenschist facies) that thus have the less altered biosignature indicative of relatively well-preserved organic matter. If comparably preserved, similar characteristics would be expected to be exhibited by microfossils or ancient organic matter in rock samples collected and cached on Mars in preparation for future sample return to Earth. [ABSTRACT FROM AUTHOR]

Novel biosignatures of laminated, microbial, digitate sedimentary structures – stromatolites – from modern geothermal fields of the Taupō Volcanic Zone, New Zealand, and from El Tatio, Chile, provide an opportunity to investigate evidence of extremophile life preserved in siliceous hot spring deposits, or sinters, interpreted as analogs for early life on Earth and possibly Mars. Synchrotron-μXRF, electron microprobe analysis, Raman spectroscopy, and optical microscopy are used in a coordinated approach to identify corroborating textural and chemical (organic, inorganic) evidence of life in these modern, opaline (amorphous) siliceous materials. Fluid mobile elements, such as As and Sr, track the growth history of the digitate structures. Trace element enrichments of Ca, Al, Ga, +/− Fe, Mn, As, Rb, Cs, and Sr, are identified in silicified sheaths of microbial filaments embedded within the sinter. In contrast, silicified diatoms in some sinter samples show no trace element enrichment. Gallium enrichments have also been observed in other 16 ka and Jurassic (150 Ma) microbial palisade sinter textures, suggesting the potential for preservation through geologic time, even after recrystallization to quartz. Raman analysis reveals spectra of organics, consistent with pigments for UV protection in cyanobacteria, in silicified sheaths around microbial filaments and are co-located with trace metal enrichments in digitate structures. Due to spectral bands, the location of these molecules (i.e., in the sheaths), and the sampling locations, we ascribe the spectra to scytonemin and carotenoid class molecules. The combined analytical approach outlined here provides a robust means to assess the validity of novel biosignatures, with application to the exploration of Mars, where preservation of opaline silica in >3.6 Ga deposits has the potential to preserve a range of microbial biosignatures. [Display omitted] • New Zealand and Chile hot spring deposits are morphological analogs for digitate silica on Mars. • Morphological, trace metal and organic biosignatures are correlated to identify evidence of life in hot spring silica. • Synchrotron trace element mapping highlights enrichments associated with microbial filament sheaths. • Gallium is the most widely preserved trace metal biosignature and may be preserved through diagenesis. • Raman spectroscopy identifies microbial pigments scytonemin and β-carotene in sheaths with trace metal enrichments. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is an aggressive form of blood cancer and clinically highly heterogeneous characterized by the accumulation of clonally proliferative immature precursors of myeloid lineage leading to bone marrow failure. Although, the current diagnostic methods for AML consist of cytogenetic and molecular assessment, there is a need for new markers that can serve as useful candidates in diagnosis, prognosis and understanding the pathophysiology of the disease. This study involves the investigation of alterations in the bone marrow interstitial fluid and serum proteome of AML patients compared to controls using label-free quantitative proteomic approach. A total of 201 differentially abundant proteins were identified in AML BMIF, while in the case of serum 123 differentially abundant proteins were identified. The bioinformatics analysis performed using IPA revealed several altered pathways including FAK signalling, IL-12 signalling and production of macrophages etc. Verification experiments were performed in a fresh independent cohort of samples using MRM assays led to the identification of a panel of three proteins viz., PPBP, APOH, ENOA which were further validated in a new cohort of serum samples by ELISA. The three-protein panel could be helpful in the diagnosis, prognosis and understanding of the pathophysiology of AML in the future. Acute Myeloid Leukemia (AML) is a type haematological malignancy which constitute one third of total leukemias and it is the most common acute leukemia in adults. In the current clinical practice, the evaluation of diagnosis and progression of AML is largely based on morphologic, immunophenotypic, cytogenetic and molecular assessment. There is a need for new markers/signatures which can serve as useful candidates in diagnosis and prognosis. The present study aims to identify and validate candidate biosignature for AML which can be useful in diagnosis, prognosis and understand the pathophysiology of the disease. Here, we identified 201 altered proteins in AML BMIF and 123 in serum. Among these altered proteins, a set of three proteins viz., pro-platelet basic protein (CXCL7), enolase 1 (ENO1) and beta-2-glycoprotein 1 (APOH) were significantly increased in AML BMIF and serum suggest that this panel of proteins could help in future AML disease management and thereby improving the survival expectancy of AML patients. [Display omitted] • Identified 201 differentially expressed proteins in AML bone marrow interstitial fluid • Identified 123 differentially expressed protein in AML serum samples • MRM-based assays identified a panel of three proteins as candidate signature • ELISA-based validation confirmed this panel as candidate biosignature for AML • CXCL7, ENO1 and APOH turned out to be important putative candidates for AML [ABSTRACT FROM AUTHOR]

Motility is a great biosignature and its pattern is characteristic for specific microbes. However, motion does also occur within the cell by the myriads of ongoing processes within the cell and the exchange of gases and nutrients with the outside environment. Here, we propose that the sum of these processes in a microbial cell is equivalent to a pulse in complex organisms and suggest a first approach to measure the “living pulse” in microorganisms. We emphasize that if a “living pulse” can be shown to exist, it would have far-reaching applications, such as for finding life in extreme environments on Earth and in extraterrestrial locations, as well as making sure that life is not present where it should not be, such as during medical procedures and in the food processing industry.

Deserts represent extreme habitats where photosynthetic life is restricted to the lithic niche. The ability of rock-inhabiting cyanobacteria to modify their photosynthetic apparatus and harvest far-red light (near-infrared) was investigated in 10 strains of the genus Chroococcidiopsis, previously isolated from diverse endolithic and hypolithic desert communities. The analysis of their growth capacity, photosynthetic pigments, and apcE2-gene presence revealed that only Chroococcidiopsis sp. CCMEE 010 was capable of far-red light photoacclimation (FaRLiP). A total of 15 FaRLiP genes were identified, encoding paralogous subunits of photosystem I, photosystem II, and the phycobilisome, along with three regulatory elements. CCMEE 010 is unique among known FaRLiP strains by undergoing this acclimation process with a significantly reduced cluster, which lacks major photosystem I paralogs psaA and psaB. The identification of an endolithic, extremotolerant cyanobacterium capable of FaRLiP not only contributes to our appreciation of this phenotype's distribution in nature but also has implications for the possibility of oxygenic photosynthesis on exoplanets. [ABSTRACT FROM AUTHOR]

Preliminary investigations on the Infrared Spectrometer onboard Mars 2020 Perseverance rover show the presence of Fe-/Mg-smectite minerals near the first drilling site, Roubion. Laser-Induced Breakdown Spectrometer data show characteristic emission peaks for O, H and the major constituent elements of smectites, viz. Si, Fe, Mg, etc. These minerals suggest aqueous alteration of the basaltic floor of the Jezero crater. The mechanically weak nature of this basalt weathering layer holds clues to the non-retrieval of the first drill core. Water confinement capacity and high porosity-permeability make the smectite-rich rock units a good host for preserving macro- and microscopic biosignatures. [ABSTRACT FROM AUTHOR]

Deserts represent extreme habitats where photosynthetic life is restricted to the lithic niche. The ability of rock-inhabiting cyanobacteria to modify their photosynthetic apparatus and harvest far-red light (near-infrared) was investigated in 10 strains of the genus Chroococcidiopsis, previously isolated from diverse endolithic and hypolithic desert communities. The analysis of their growth capacity, photosynthetic pigments, and apcE2-gene presence revealed that only Chroococcidiopsis sp. CCMEE 010 was capable of far-red light photoacclimation (FaRLiP). A total of 15 FaRLiP genes were identified, encoding paralogous subunits of photosystem I, photosystem II, and the phycobilisome, along with three regulatory elements. CCMEE 010 is unique among known FaRLiP strains by undergoing this acclimation process with a significantly reduced cluster, which lacks major photosystem I paralogs psaA and psaB. The identification of an endolithic, extremotolerant cyanobacterium capable of FaRLiP not only contributes to our appreciation of this phenotype’s distribution in nature but also has implications for the possibility of oxygenic photosynthesis on exoplanets.

The identification of traces of life beyond Earth (e.g., Mars, icy moons) is a challenging task because terrestrial chemical-based molecules may be destroyed by the harsh conditions experienced on extraterrestrial planetary surfaces. For this reason, studying the effects on biomolecules of extremophilic microorganisms through astrobiological ground-based space simulation experiments is significant to support the interpretation of the data that will be gained and collected during the ongoing and future space exploration missions. Here, the stability of the biomolecules of the cryptoendolithic black fungus Cryomyces antarcticus , grown on two Martian regolith analogues and on Antarctic sandstone, were analysed through a metabolomic approach, after its exposure to Science Verification Tests (SVTs) performed in the frame of the European Space Agency (ESA) Biology and Mars Experiment (BIOMEX) project. These tests are building a set of ground-based experiments performed before the space exposure aboard the International Space Station (ISS). The analysis aimed to investigate the effects of different mineral mixtures on fungal colonies and the stability of the biomolecules synthetised by the fungus under simulated Martian and space conditions. The identification of a specific group of molecules showing good stability after the treatments allow the creation of a molecular database that should support the analysis of future data sets that will be collected in the ongoing and next space exploration missions. [ABSTRACT FROM AUTHOR]

The identification of traces of life beyond Earth (e.g., Mars, icy moons) is a challenging task because terrestrial chemical-based molecules may be destroyed by the harsh conditions experienced on extraterrestrial planetary surfaces. For this reason, studying the effects on biomolecules of extremophilic microorganisms through astrobiological ground-based space simulation experiments is significant to support the interpretation of the data that will be gained and collected during the ongoing and future space exploration missions. Here, the stability of the biomolecules of the cryptoendolithic black fungus Cryomyces antarcticus, grown on two Martian regolith analogues and on Antarctic sandstone, were analysed through a metabolomic approach, after its exposure to Science Verification Tests (SVTs) performed in the frame of the European Space Agency (ESA) Biology and Mars Experiment (BIOMEX) project. These tests are building a set of ground-based experiments performed before the space exposure aboard the International Space Station (ISS). The analysis aimed to investigate the effects of different mineral mixtures on fungal colonies and the stability of the biomolecules synthetised by the fungus under simulated Martian and space conditions. The identification of a specific group of molecules showing good stability after the treatments allow the creation of a molecular database that should support the analysis of future data sets that will be collected in the ongoing and next space exploration missions.