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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 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]

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.

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]

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.

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]

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.

Priorities for the exploration of Mars involve the identification and observation of biosignatures that indicate the existence of life on the planet. The atmosphere and composition of the sediments on Mars suggest suitability for anaerobic chemolithotrophic metabolism. Carbonates are often considered as morphological biosignatures, such as stromatolites, but have not been considered as potential electron acceptors. Within the present study, hydrogenotrophic methanogen enrichments were generated from sediments that had received significant quantities of lime from industrial processes (lime kiln/steel production). These enrichments were then supplemented with calcium carbonate powder or marble chips as a sole source of carbon. These microcosms saw a release of inorganic carbon into the liquid phase, which was subsequently removed, resulting in the generation of methane, with 0.37 ± 0.09 mmoles of methane observed in the steel sediment enrichments supplemented with calcium carbonate powder. The steel sediment microcosms and lime sediments with carbonate powder enrichments were dominated by Methanobacterium sp., whilst the lime/marble enrichments were more diverse, containing varying proportions of Methanomassiliicoccus, Methanoculleus and Methanosarcina sp. In all microcosm experiments, acetic acid was detected in the liquid phase. Our results indicate that chemolithotrophic methanogenesis should be considered when determining biosignatures for life on Mars. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential of host urinary biomarkers as diagnostic candidates for tuberculosis (TB). Methods: Adults self-presenting with symptoms requiring further investigation for TB were enrolled in Cape Town, South Africa. Participants were later classified as having TB or other respiratory diseases (ORD) using results from TB confirmatory tests. The concentrations of 29 analytes were evaluated in urine samples from participants using the Luminex platform, and their diagnostic potential was assessed using standard statistical approaches. Results: Of the 151 study participants, 34 (22.5%) were diagnosed with TB and 26 (17.2%) were HIV-positive. Seven biomarkers showed potential as TB diagnostic candidates, with accuracy improving (in HIV-positives) when stratified according to HIV status (area under the receiver operating characteristics curve; AUC ≥0.80). In HIV-positive participants, a four-marker biosignature (sIL6R, MMP-9, IL-2Ra, IFN-γ) diagnosed TB with AUC of 0.96, sensitivity of 85.7% (95% confidence interval (CI) 42.1–99.6%), and specificity of 94.7% (95% CI 74.0–99.9%). In HIV-negatives, the most promising was a two-marker biosignature (sIL6R and sIL-2Ra), which diagnosed TB with AUC of 0.76, sensitivity of 53.9% (95% CI 33.4–73.4%), and specificity of 79.6% (95% CI 70.3–87.1%). Conclusions: Urinary host inflammatory biomarkers possess TB diagnostic potential but may be influenced by HIV infection. The results of this study require validation in larger studies.

In July 2020, NASA’s Perseverance (Mars 2020) mission was launched. The rover sent to the surface of Mars will not only perform in situ analyses, but will also collect rock and regolith samples that will be returned to Earth by future missions for further investigations. Therefore, the amount and quality of astrobiological data retrieved from these missions is expected to be unprecedented. The challenge faced by the astrobiology community will be to use these data in the most efficient way to assess whether any of the analysed samples are of biogenic origin. However, in situ biogenic assessments often lack quantitative support. Particularly, their statistical uncertainty is not systematically evaluated. This study aims to provide the first quantitative framework that evaluates the uncertainty of in situ biogenic assessments using recursive Bayesian statistics. Our results show that detecting more than seven potential biosignatures does not increase the reliability of biogenic assessments, unless the probability of detection of biosignatures in the sample and the probability of the biosignatures being false positives are well constrained. This study emphasizes the need for quantitative support of biogenic assessments and astrobiology strategies in general.

The signatures of element isotope fractionation can be used for the indirect identification of extant or extinct life on planetary surfaces or their moons. Element isotope fractionation signatures are very robust against the harsh environmental conditions, such as temperature or irradiation, which typically prevail on solar system bodies. Sulphur is a key element for life as we know it and bacteria exist, such as sulphur reducing bacteria, that can metabolize sulphur resulting in isotope fractionations of up to −70‰ δ34S. Geochemical processes are observed to fractionate up to values of −20‰ δ34S hence, fractionation exceeding that value might be highly indicative for the presence of life. However, the detection of sulphur element isotope fractionation in situ, under the assumption that life has existed or still does exist, is extremely challenging. To date, no instrument developed for space application showed the necessary detection sensitivity or measurement methodology for such an identification. In this contribution, we report a simple measurement protocol for the accurate detection of sulphur fractionation δ34S using our prototype laser ablation ionization mass spectrometer system designed for in situ space exploration missions. The protocol was elaborated based on measurements of five sulphur containing species that were sampled at different Mars analogue field sites, including two cave systems in Romania and the Río Tinto river environment in Spain. Optimising the laser pulse energy of our laser ablation ionization mass spectrometer (LIMS) allowed the identification of a peak-like trend of the 34S/32S ratio, where the maximum, compared to internal standards, allowed to derive isotope fractionation with an estimated δ34S accuracy of ∼2‰. This accuracy is sufficiently precise to differentiate between abiotic and biotic signatures, of which the latter, induced by, e.g., sulphate-reducing microorganism, may fractionate sulphur isotopes by more than −70‰ δ34S. Our miniature LIMS system, including the discussed measurement protocol, is simple and can be applied for life detection on extra-terrestrial surfaces, e.g., Mars or the icy moons like Europa.

Abstract Pyrite (FeS2) is the most common iron sulfide on the Earth's surface and has widely been used as a paleo‐environmental proxy. Yet the information recorded by pyrite depends on whether it was formed through abiotic or biogenic routes. It is thus of importance to properly identify its origin. Here, we investigate the final morphology of pyrite produced upon a simulated diagenetic history from biogenic and abiotic iron sulfide/phosphate systems. Abiotic starting material obtained by chemical synthesis and biogenic starting material produced from pure culture of Desulfovibrio desulfuricans were submitted to increasing diagenetic conditions (75°C or 150°C from 1 to 10 days). Mineralogical products were characterized by X‐ray diffraction and electron microscopy. For both biogenic and abiotic starting materials, the final state was characterized by the association of pyrite and lipscombite (Fe2+Fe23+(OH)2(PO4)2), the most stable phases in these conditions. Intermediate phases such as greigite for iron sulfides and beraunite/wolfeite for iron phosphates were present in the abiotic residue but were not detected in the biogenic residue. Distinct pyrite morphologies were observed depending on the presence of organic matter. Indeed, while abiotic starting material led to the formation of submicrometric single crystals of pyrite with euhedral shapes similar to the subunits of well crystallized framboids, biogenic starting material produced micrometric spherulitic clusters of pyrite resembling the so‐called pseudo‐framboids. Although further experiments are required to ensure that it can be used as biosignatures, such specific morphologies, likely related to the presence of organic matter, may help recognizing biogenic pyrite in the geological record.

Nitrogen-containing heterocyclic compounds are fundamental biochemical components of all life on Earth and, presumably, life elsewhere in our solar system. Detection and characterization of these compounds by traditional solvent extraction, chromatographic separation, and GC–MS analysis require more sample mass than will be available from samples returned to Earth from Mars. With its small sample mass requirement, Surface Enhanced Raman Spectroscopy could be an appropriate technique for analysis of returned samples. We have developed a SERS method for the detection of maleimide (2,5-pyrroledione), an N-containing heterocycle with a structure that is widespread in biochemicals. This semi-quantitative methodology accurately determines maleimide concentration in the range from 60 µg/mL to 120 µg/mL. We present a maleimide SERS standard spectrum which will be useful as a reference for future works. The present work demonstrates an easy, accurate, and effective method for the non-destructive qualitative and semi-quantitative study of maleimide as a first step toward developing a method for analysis of related compounds.

In the search for life on other planets, the presence of photosynthetic surface vegetation may be detectable from the colors of light it reflects. On the modern Earth, this spectral reflectance is characterized by a steep increase in reflectance between the red and near‐infrared wavelengths, a signature known as the “red edge”. This edge-like signature occurs at wavelengths of peak photon absorbance, which are the result of adaptations of the phototroph to their spectral environment. On planets orbiting different stellar types, red edge analogs may occur at other colors than red. Thus, knowing the wavelengths at which photosynthetic organisms preferentially absorb and reflect photons is necessary to detect red edge analogs on other planets. Using a numerical model that predicts the absorbance spectrum of extant photosynthetic pigments on Earth from Marosvölgyi and van Gorkom (2010), we calculate the absorbance spectrum for pigments on an Earth-like planet around F through late M type stars that are adapted for maximal energy production. In this model, cellular energy production is maximized when pigments are tuned to absorb at the wavelength that maximizes energy input from incident photons while minimizing energy losses due to thermal emission and building cellular photosynthetic apparatus. We find that peak photon absorption for photosynthetic organisms around F type stars tends to be in the blue while for G, K, and early M type stars, red or just beyond is preferred. Around the coolest M type stars, these organisms may preferentially absorb in the near-infrared, possibly past one micron. These predictions are consistent with previous, qualitative estimates of pigment absorptance. Our predicted absorbance spectra for photosynthetic surface organisms depend on both the stellar type and planetary atmospheric composition, especially atmospheric water vapor concentrations, which alter the availability of surface photons and thus the predicted pigment absorption. By constraining the absorbance spectra of alien, photosynthetic organisms, future observations may be better equipped to detect the weak spectral signal of red edge analogs.

Major depressive disorder (MDD) is a pleomorphic illness originating from gene x environment interactions. Patients with differing symptom phenotypes receive the same diagnosis and similar treatment recommendations without regard to genomics, brain structure or function, or other physiologic or psychosocial factors. Using this present approach, only one third of patients enter remission with the first medication prescribed, and patients may take longer than 1 year to enter remission with repeated trials. Research to improve treatment effectiveness recently has focused on identification of intermediate phenotypes (IPs) that could parse the heterogeneous population of patients with MDD into subgroups with more homogeneous responses to treatment. Such IPs could be used to develop biomarkers that could be applied clinically to match patients with the treatment that would be most likely to lead to remission. Putative biomarkers include genetic polymorphisms, RNA and protein expression (transcriptome and proteome), neurotransmitter levels (metabolome), additional measures of signaling cascades, oscillatory synchrony, neuronal circuits and neural pathways (connectome), along with other possible physiologic measures. All of these measures represent components of a continuum that extends from proximity to the genome to proximity to the clinical phenotype of depression, and there are many levels along this continuum at which useful IPs may be defined. Because of the highly integrative nature of brain systems and the complex neurobiology of depression, the most useful biomarkers are likely to be those with intermediate proximity both to the genome and the clinical phenotype of MDD. Translation of findings across the spectrum from genotype to phenotype promises to better characterize the complex disruptions in signaling and neuroplasticity that accompany MDD, and ultimately to lead to greater understanding of the causes of depressive illness.

Abstract Oxygen is a promising exoplanet biosignature due to the evolutionary advantage conferred by harnessing starlight for photosynthesis, and the apparent low likelihood of maintaining oxygen‐rich atmospheres without life. Hypothetical scenarios have been proposed for non‐biological oxygen accumulation on planets around late M‐dwarfs, where the extended pre‐main sequence may favor abiotic O2 accumulation. In contrast, abiotic oxygen accumulation on planets around F, G, and K‐type stars is seemingly less likely, provided they possess substantial non‐condensable gas inventories. The comparative robustness of oxygen biosignatures around larger stars has motivated plans for next‐generation telescopes capable of oxygen detection on planets around sun‐like stars. However, the general tendency of terrestrial planets to develop oxygen‐rich atmospheres across a broad range of initial conditions and evolutionary scenarios has not been explored. Here, we use a coupled thermal‐geochemical‐climate model of terrestrial planet evolution to illustrate three scenarios whereby significant abiotic oxygen can accumulate around sun‐like stars, even when significant noncondensable gas inventories are present. For Earth‐mass planets, we find abiotic oxygen can accumulate to modern levels if (1) the CO2:H2O ratio of the initial volatile inventory is high, (2) the initial water inventory exceeds ∼50 Earth oceans, or (3) the initial water inventory is very low (

Cosmos has always sparked human curiosity to unveil and speculate its fascinating secrets. This curiosity has ultimately opened a window to other worlds. After years of observation, computation, and data analysis, scientists have revealed the diversity in exoplanets that have been helpful in the characterization and further investigation of biosignatures and technosignatures. This article presents some of the scientific advances made in extraterrestrial planetary science that guarantees to search through the thick clouds of the mysterious planets in the near future. [ABSTRACT FROM AUTHOR]

Priorities for the exploration of Mars involve the identification and observation of biosignatures that indicate the existence of life on the planet. The atmosphere and composition of the sediments on Mars suggest suitability for anaerobic chemolithotrophic metabolism. Carbonates are often considered as morphological biosignatures, such as stromatolites, but have not been considered as potential electron acceptors. Within the present study, hydrogenotrophic methanogen enrichments were generated from sediments that had received significant quantities of lime from industrial processes (lime kiln/steel production). These enrichments were then supplemented with calcium carbonate powder or marble chips as a sole source of carbon. These microcosms saw a release of inorganic carbon into the liquid phase, which was subsequently removed, resulting in the generation of methane, with 0.37 ± 0.09 mmoles of methane observed in the steel sediment enrichments supplemented with calcium carbonate powder. The steel sediment microcosms and lime sediments with carbonate powder enrichments were dominated by Methanobacterium sp., whilst the lime/marble enrichments were more diverse, containing varying proportions of Methanomassiliicoccus, Methanoculleus and Methanosarcina sp. In all microcosm experiments, acetic acid was detected in the liquid phase. Our results indicate that chemolithotrophic methanogenesis should be considered when determining biosignatures for life on Mars.

Limited taxonomic classification is possible for Archaean microbial mats and this is a fundamental limitation in constraining early ecosystems. Applying Fourier transform infrared spectroscopy (FTIR), a powerful tool for identifying vibrational motions attributable to specific functional groups, we characterized fossilized biopolymers in 3.5–3.3 Ga microbial mats from the Barberton greenstone belt (South Africa). Microbial mats from four Palaeoarchaean horizons exhibit significant differences in taxonomically informative aliphatic contents, despite high aromaticity. This reflects precursor biological heterogeneity since all horizons show equally exceptional preservation and underwent similar grades of metamorphism. Low methylene to end‐methyl (CH2/CH3) absorbance ratios in mats from the 3.472 Ga Middle Marker horizon signify short, highly branched n‐alkanes interpreted as isoprenoid chains forming archaeal membranes. Mats from the 3.45 Ga Hooggenoeg Chert H5c, 3.334 Ga Footbridge Chert, and 3.33 Ga Josefsdal Chert exhibit higher CH2/CH3 ratios suggesting mostly longer, unbranched fatty acids from bacterial lipid precursors. Absorbance ratios of end‐methyl to methylene (CH3/CH2) in Hooggenoeg, Josefsdal and Footbridge mats yield a range of values (0.20–0.80) suggesting mixed bacterial and archaeal architect communities based on comparison with modern examples. Higher (0.78–1.25) CH3/CH2 ratios in the Middle Marker mats identify Archaea. This exceptional preservation reflects early, rapid silicification preventing the alteration of biogeochemical signals inherited from biomass. Since silicification commenced during the lifetime of the microbial mat, FTIR signals estimate the affinities of the architect community and may be used in the reconstruction of Archaean ecosystems. Together, these results show that Bacteria and Archaea flourished together in Earth's earliest ecosystems. [ABSTRACT FROM AUTHOR]

• Twenty-nine host biomarkers were evaluated in urine samples obtained from TB suspects. • Seven individual biomarkers showed potential as promising diagnostic candidates. • A four-marker urinary biosignature diagnosed TB with high accuracy in HIV-positive participants. • Urinary inflammatory protein biomarkers are promising as TB diagnostic candidates. To investigate the potential of host urinary biomarkers as diagnostic candidates for tuberculosis (TB). Adults self-presenting with symptoms requiring further investigation for TB were enrolled in Cape Town, South Africa. Participants were later classified as having TB or other respiratory diseases (ORD) using results from TB confirmatory tests. The concentrations of 29 analytes were evaluated in urine samples from participants using the Luminex platform, and their diagnostic potential was assessed using standard statistical approaches. Of the 151 study participants, 34 (22.5%) were diagnosed with TB and 26 (17.2%) were HIV-positive. Seven biomarkers showed potential as TB diagnostic candidates, with accuracy improving (in HIV-positives) when stratified according to HIV status (area under the receiver operating characteristics curve; AUC ≥0.80). In HIV-positive participants, a four-marker biosignature (sIL6R, MMP-9, IL-2Ra, IFN-γ) diagnosed TB with AUC of 0.96, sensitivity of 85.7% (95% confidence interval (CI) 42.1–99.6%), and specificity of 94.7% (95% CI 74.0–99.9%). In HIV-negatives, the most promising was a two-marker biosignature (sIL6R and sIL-2Ra), which diagnosed TB with AUC of 0.76, sensitivity of 53.9% (95% CI 33.4–73.4%), and specificity of 79.6% (95% CI 70.3–87.1%). Urinary host inflammatory biomarkers possess TB diagnostic potential but may be influenced by HIV infection. The results of this study require validation in larger studies. [ABSTRACT FROM AUTHOR]

Background: Our study aimed to identify a host cytokine biosignature that could distinguish childhood tuberculosis (TB) from other respiratory diseases (OD). Methods: Cytokine responses in prospectively recruited children with symptoms suggestive of TB were measured in whole blood assay supernatants, harvested after overnight incubation, using a Luminex platform. We used logistic regression models with Least Absolute Shrinkage and Selection Operator (LASSO) penalty to identify the optimal biosignature associated with confirmed TB disease in the training set. We subsequently assessed its performance in the test set. Findings: Of the 431 children included in the study, 44 had bacteriologically confirmed TB, 60 had clinically diagnosed TB while 327 had OD. All children were HIV-negative. Application of LASSO regression models to the training set (n = 260) resulted in the combination of IL-1ra, IL-7 and IP-10 from unstimulated samples as the optimally discriminant cytokine biosignature associated with bacteriologically confirmed TB. In the test set (n = 171), this biosignature distinguished children diagnosed with TB disease, irrespective of microbiological confirmation, from OD with area under the receiver operator characteristic curve (AUC) of 0•74 (95% CI: 0•67, 0•81), and demonstrated sensitivity and specificity of 72•2% (95% CI: 60•4, 82•1%) and 75•0% (95% CI: 64•9, 83•4%) respectively, with its performance independent of their age group and their age- and sex-adjusted nutritional status. Interpretation: This novel biosignature of childhood TB derived from unstimulated supernatants is promising. Independent validation with further optimisation will improve its performance and translational potential. Funding: Steinberg Fellowship (McGill University); Grand Challenges Canada; MRC Program Grant.

ABSTRACT In tuberculosis (TB), as in other infectious diseases, studies of small noncoding RNAs (sncRNA) in peripheral blood have focused on microRNAs (miRNAs) but have neglected the other major sncRNA classes in spite of their potential functions in host gene regulation. Using RNA sequencing of whole blood, we have therefore determined expression of miRNA, PIWI-interacting RNA (piRNA), small nucleolar RNA (snoRNA), and small nuclear RNA (snRNA) in patients with TB (n = 8), latent TB infection (LTBI; n = 21), and treated LTBI (LTBItt; n = 6) and in uninfected exposed controls (ExC; n = 14). As expected, sncRNA reprogramming was greater in TB than in LTBI, with the greatest changes seen in miRNA populations. However, substantial dynamics were also evident in piRNA and snoRNA populations. One miRNA and 2 piRNAs were identified as moderately accurate (area under the curve [AUC] = 0.70 to 0.74) biomarkers for LTBI, as were 1 miRNA, 1 piRNA, and 2 snoRNAs (AUC = 0.79 to 0.91) for accomplished LTBI treatment. Logistic regression identified the combination of 4 sncRNA (let-7a-5p, miR-589-5p, miR-196b-5p, and SNORD104) as a highly sensitive (100%) classifier to discriminate TB from all non-TB groups. Notably, it reclassified 8 presumed LTBI cases as TB cases, 5 of which turned out to have features of Mycobacterium tuberculosis infection on chest radiographs. SNORD104 expression decreased during M. tuberculosis infection of primary human peripheral blood mononuclear cells (PBMC) and M2-like (P = 0.03) but not M1-like (P = 0.31) macrophages, suggesting that its downregulation in peripheral blood in TB is biologically relevant. Taken together, the results demonstrate that snoRNA and piRNA should be considered in addition to miRNA as biomarkers and pathogenesis factors in the various stages of TB. IMPORTANCE Tuberculosis is the infectious disease with the worldwide largest disease burden and there remains a great need for better diagnostic biomarkers to detect latent and active M. tuberculosis infection. RNA molecules hold great promise in this regard, as their levels of expression may differ considerably between infected and uninfected subjects. We have measured expression changes in the four major classes of small noncoding RNAs in blood samples from patients with different stages of TB infection. We found that, in addition to miRNAs (which are known to be highly regulated in blood cells from TB patients), expression of piRNA and snoRNA is greatly altered in both latent and active TB, yielding promising biomarkers. Even though the functions of many sncRNA other than miRNA are still poorly understood, our results strongly suggest that at least piRNA and snoRNA populations may represent hitherto underappreciated players in the different stages of TB infection.

Microorganisms may play an important role in the aggregation of sediments and the formation of sedimentary structures. Biofilms are microbial aggregates that, in a mature stage, can develop into microbial mats, fibrillar networks that irreversibly bind filaments of cyanobacteria and sediments, inside which it has been identified a stratification with functional groups of microorganisms that coexist, generate symbiotic relationships and potentially modify the characteristics of sediments and sedimentary rocks, particularly in extreme environments. In this work, filamentous cyanobacteria from biofilms of a lacustrine environment with intervals of flooding/desiccation and a saline environment, and a microbial mat from the Agua Caliente Thermal, El Rosal, Cundinamarca, are identified. In the biofilms, most cyanobacteria were found to belong to the Orden Oscillatoriales, while in the microbial mat cyanobacteria of the order Orden Nostocales were also recognized. Two rock samples isolated from the thermal which genesis was possibly influenced by the activity of cyanobacteria are described and classified. One of them, named R-1, is a calcareous rock inside which it was possible to differentiate biolaminations and an apparent dominance of biomineralization processes. This sample was both classified as a travertine and a microbial framestone with stromatolitic and thrombolytic texture. The second one, called R-2, is a siliciclastic rock classified as a mudstone and a microbial boundstone. Finally, a comparison between the sedimentary structures identified in those rocks with similar structures in the formations La Luna, Paja and Tetuán and the microbially-induced sedimentary structures (MISS) described in the literature is performed. Based on morphological resemblance, fibrillar networks identified locally in those formations are interpreted as possible biolaminations originated from the activity of cyanobacteria.

Atmospheric composition is an important indicator of habitability and life. The presence or absence of a large exomoon around an Earth-size exoplanet could have important consequences for planet climate stability. Thus the detection of exomoons and retrieval of information regarding atmospheric composition of Earth-size exoplanets are important goals of future exoplanet observations. Here a data analysis method is developed to achieve both goals simultaneously, based on reflection spectra of exoplanet-exomoon systems. We show that the existence of exomoons, the size of exomoons, and the concentrations of some atomic and molecular species in the atmospheres of their hosting Earth-like exoplanets can be retrieved with high levels of reliability. In addition, the method can provide well-constrained fractions of basic surface types on the targets because of the characteristic spectral features of atmospheric species and surface types in the analyzed spectral range.

The success of an astrobiological search for life campaign on Mars, or other planetary bodies in the Solar System, relies on the detectability of past or present microbial life traces, namely, biosignatures. Spectroscopic methods require little or no sample preparation, can be repeated almost endlessly, and can be performed in contact or even remotely. Such methods are therefore ideally suited to use for the detection of biosignatures, which can be confirmed with supporting instrumentation. Here, we discuss the use of Raman and Fourier Transform Infrared (FT-IR) spectroscopies for the detection and characterization of biosignatures from colonies of the fungus Cryomyces antarcticus, grown on Martian analogues and exposed to increasing doses of UV irradiation under dried conditions. The results report significant UV-induced DNA damage, but the non-exceeding of thresholds for allowing DNA amplification and detection, while the spectral properties of the fungal melanin remained unaltered, and pigment detection and identification was achieved via complementary analytical techniques. Finally, this work found that fungal cell wall compounds, likely chitin, were not degraded, and were still detectable even after high UV irradiation doses. The implications for the preservation and detection of biosignatures in extraterrestrial environments are discussed.

Silica has the highest demonstrated potential of any phase to preserve microfossils on Earth and therefore may host potential biosignatures on Mars. We detected hydrated silica in Jezero crater, the landing site of the National Aeronautics and Space Administration's Mars 2020 rover mission, by applying Dynamic Aperture Factor Analysis/Target Transformation to images from the Compact Reconnaissance Imaging Spectrometer for Mars. Hydrated silica detections with Dynamic Aperture Factor Analysis/Target Transformation were verified using commonly accepted Compact Reconnaissance Imaging Spectrometer for Mars analysis methods. The morphology of geologic units associated with silica was characterized with high‐resolution imaging. Several hypotheses are presented for the formation environment of hydrated silica. All are testable via in situ investigation. We assess the likelihood of silica to preserve biosignatures in these different scenarios based on habitability considerations and biosignature preservation in Earth analog environments and materials. Also reported are possible detections of hydrated silica in the Nili Fossae basement and olivine‐rich units, as well as Al‐phyllosilicate within Jezero crater. Key Points: Hydrated silica is detected in Jezero crater and could have formed in a variety of environments with different degrees of habitabilityHydrated silica is associated with smooth dark‐toned material that covers the olivine‐rich unitHydrated silica in Jezero crater is an excellent target for in situ investigation for biosignatures [ABSTRACT FROM AUTHOR]