Search Results (149)

Background and Objectives: Major Depressive Disorder (MDD) and Bipolar Disorder (BD) lack objective molecular stratification despite partial clinical overlap, particularly during depressive phases. This cross-sectional study explored whether coordinated peripheral biomarker patterns could be identified using an integrated multivariate analytical framework. Materials and Methods: A total of 151 participants (MDD n = 41; BD n = 40; HC (healthy controls) n = 70) were profiled for 42 blood-derived parameters including composite inflammatory indices, hematological markers, trace elements measured by ICP-MS, and circulating BDNF and NLRP3 quantified by ELISA. Data were analyzed using univariate testing, unsupervised dimensionality reduction (PCA, t-SNE), and supervised classification (PLS-DA with cross-validation and permutation testing). Results: Thirty-seven of 42 parameters showed significant inter-group differences (p < 0.05). Circulating NLRP3 concentrations were markedly reduced in both psychiatric groups compared with HC. Composite inflammatory indices (NLR, SIRI, SII) were elevated in MDD. Zinc levels were modestly reduced, while manganese levels were increased in psychiatric cohorts. BDNF showed lower concentrations in MDD and higher concentrations in BD relative to HC. Cross-validated PLS-DA classification for psychiatric disorder vs. controls yielded an accuracy of 89.4% (AUC-ROC 0.947), with permutation testing indicating performance above chance. However, the sample-to-variable ratio and exploratory design warrant cautious interpretation. Conclusions: Multidomain peripheral biomarker profiling identified coordinated biochemical differences across diagnostic groups. These findings suggest the presence of multidimensional peripheral signatures associated with mood disorders within an exploratory framework. Full article

Methanogens, or methanogenic archaea (MA), are among the most ancient and widely distributed microorganisms, characterized by a unique metabolism that generates methane (CH₄) as the terminal product of anaerobic respiration. Their ability to grow and/or survive across a wide range of environmental conditions has made methanogens key contributors to biogeochemical cycles throughout most of Earth’s history. Most importantly, these oxygen-sensitive microorganisms have regulated the climate since the early Archean and impacted biogeochemical cycles throughout Earth’s history by producing the potent greenhouse gas, CH₄, while consuming H₂, CO₂, and small organic molecules. Hence, methanogens are attributed a key role in the start and end of several Proterozoic glaciations and mass extinction events. Their specific roles in the long-term carbon cycle that focus on CH₄ production are well-established, but, in contrast, only very few studies report on interactions with CaCO₃ and long-term carbon storage. Methanogens evolved early during Earth’s history, likely during the Archaean Eon, in layered benthic microbial communities called microbial mats. When lithified, these mats form microbialites that represent some of the earliest evidence of life in the fossil record, dating back >3.5 Gy. Methanogens are an integral part of contemporary microbial mats and have been identified both in the anoxic and oxic zones of these sedimentary ecosystems; however, their adaptations to apparently unfavorable oxic conditions and their role in the precipitation of carbonate in mats are unclear. In addition to an important role in the evolution of our planet by producing CH₄, methanogens may also produce a biosignature that could be relevant for astrobiology research. This review will discuss the diversity, physiology, and ecology of methanogens in detail to clarify their role in some of the major biogeochemical processes and ecological climatic events through the fluctuating environmental conditions on Earth through geologic time. Full article

Within the payloads of JUICE and Europa Clipper, there are instruments suitable for the search of specific biosignatures that can diagnose life tracks in two ways. The payloads include mass spectrometers capable of measuring isotopic abundances for identifying life, and chromatography instruments testing whether ocean worlds harbor amphiphile mixtures, which would lead to a lipid-first origin of life. In this paper we describe how the two missions may begin to test whether there may be large detectable excursions of stable isotopes of chemical elements on the icy surfaces of the Jovian icy moons that are substantially shifted from their expected isotopic distributions. The detection of an unambiguous signal would suggest a biogenic origin, provided care is taken to exclude abiotic thermal isotopic fractionation. Our suggested tests should be confirmed independently with other techniques. Stable isotope geochemistry on the icy Jovian moons has not yet been thoroughly discussed in the literature. In addition, we enquire whether insights into life’s origin could be retrieved from Europa’s ocean and surface, including the question of the first steps in the evolution of life. Special emphasis has been put on an approach to seek on the surface of ocean worlds chemical phenomena that are rather primitive, such as reproducing lipid micelles as roots of protocells, but nevertheless can predict a path towards life with published models. Full article

Congenital Cytomegalovirus (cCMV) infection is associated with numerous long-term sequelae. This scoping review consolidates existing evidence on fetal and neonatal immune response to cCMV and their potential relevance to clinical outcomes. A systematic search was conducted in the PubMed database. Observational studies were eligible when full text was available in English and data for immune response (innate, humoral, cellular) and/or immune-related biomarkers (cytokines and molecular markers) were provided. Thirty-four studies were included. CMV-infected fetuses mount robust γδ and CD8⁺ T-cell responses from the second trimester of pregnancy, with the transcriptomic and cytokine profile of their amniotic fluid revealing upregulation of IFN-γ-inducible genes and cytokines. cCMV-infected neonates mount oligoclonal γδ T-cell responses and functional NK and CD8⁺ T-cell responses, although data on the latter’s association with symptoms at birth are contradictory. Conversely, CD4⁺ T-cell responses are impaired, irrespective of symptoms. T cell exhaustion is an emerging finding with unclear implications on long-term outcome. Despite shared transcriptomic profiles between symptomatic and asymptomatic neonates, a 16-gene classifier biosignature has been identified for late-onset sensorineural hearing loss. In conclusion, immune response to cCMV is characterized by a Th1 signature, with T cell exhaustion being an emerging finding warranting further investigation. Full article

Chemical complexity is not a nuisance to be minimized in origin of life research, it is an enabling condition. This second edition of the Special Issue on the Origin of Life in Chemically Complex Messy Environments gathers contributions that embrace multicomponent mixtures, dynamic geochemical settings, and nonequilibrium processes. The papers collected here survey surface hydrothermal routes to reactive nitriles, groundwater evolution of alkaline lakes, and transition metal sulfide-driven amino acid and amide formation without cyanide. They report one pot nucleoside and nucleotide synthesis from formamide over cerium phosphate, review non aqueous organophosphorus pathways, and probe peptide rich mixtures and formose type networks under serpentinization associated minerals. The issue also advances conceptual frameworks, including atmospheric photochemical signatures for biosignature discrimination, the role of chiral mineral surfaces in enantioseparation, and computational simulations of the origin of LUCA. Together, these studies position messy chemistry as a crucible that turns chemical diversity and environmental heterogeneity into routes toward organization and function. Full article

Background: This study aimed to analyze metabolic changes in blood samples from patients with confirmed COVID-19 to explore the correlation between metabolomics and cytokines in survivors and non-survivors of SARS-CoV-2 infection. Understanding the complex biochemical and immunometabolic mechanisms underlying SARS-CoV-2 infection is essential for elucidating the pathophysiology and virulence of COVID-19. Methods: This study included 40 hospitalized COVID-19 patients and 40 healthy controls. Serum metabolic profiles were analyzed using ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS), and cytokine levels were measured using ELISA. Results: Our study defined three clear metabolic phenotypes among survivors and non-survivors of COVID-19 compared with healthy controls, which might be related to mortality, severity, and disease burden. A strong relationship was observed between certain inflammatory markers, including IL-1β, IL-2, IFN-β, IFN-γ, IL-17, and GM-CSF, as well as several metabolites, particularly in COVID-19 non-survivors, such as LysoPCs, 3-hydroxykynurenine, and serotonin. Different metabolite-cytokine correlation patterns were observed according to patient outcomes, indicating unique correlations between metabolic and immune responses in survivors and non-survivors. Metabolic phenotypes were associated with clinical outcomes, comorbidities, and sex-related differences. Kynurenine and related metabolites of tryptophan metabolism were closely correlated with COVID-19 severity, age, and mortality. Compared with survivors and healthy controls, non-survivors displayed higher IL-6, together with distinct metabolic changes. These included increased kynurenine through the IDO1 pathway, elevated glucose and lactate reflecting hyperglycolysis and energy stress, and higher xanthosine from purine turnover. Stronger cytokine–metabolite correlations in this group point to tightly linked immunometabolic activation. Conclusions: Metabolomic profiling revealed distinct metabolic phenotypes that could be associated with the severity and inflammation levels of COVID-19. Correlation analysis between metabolites and cytokines demonstrated strong intercorrelations between specific metabolites and cytokines, indicating a strong interrelationship between inflammatory markers and metabolic alterations. Specific metabolic pathways associated with cytokines and their clinical relevance may serve as potential therapeutic targets. Full article

Extreme environments, such as hypersaline habitats, hot springs, deep-sea hydrothermal vents, glaciers, and permafrost, provide diverse ecological niches for studying microbial evolution. However, knowledge of microbial communities in extreme environments at high southern latitudes remains limited, aside from Antarctica. Laguna Timone is a hypersaline crater lake located in a Pleistocene maar of the Pali Aike Volcanic Field, southern Patagonia; the lake was formed during basaltic eruptions in a periglacial setting. Here, we report the first integrative characterization of microbial communities from biofilms and microbial mats in this lake using high-throughput 16S rRNA and ITS gene sequencing, along with mineralogical and hydrochemical analyses of water, sediments, and carbonates. Bacterial communities were dominated by the genera Enterobacterales ASV1, Pseudomonas, Oscillatoria, Nodularia, and Belliella, with site-specific assemblages. Fungal communities included Laetinaevia, Ilyonectria, Thelebolus, Plectosphaerella, and Acrostalagmus, each showing distinct distribution patterns. These baseline data contribute to understanding microbial dynamics in hypersaline maar environments and support future investigations. This integrative approach highlights key microbe–mineral relationships and underscores the potential of Laguna Timone as a natural laboratory for exploring biosignature formation and microbial adaptation in chemically extreme environments, both on early Earth and potentially beyond. Full article

Depression represents one of the most prevalent mental health disorders globally, significantly impacting quality of life and posing substantial healthcare challenges. Traditional diagnostic methods rely on subjective assessments and clinical interviews, often leading to misdiagnosis, delayed treatment, and suboptimal outcomes. Recent advances in biosensing technologies offer promising avenues for objective depression assessment through detection of relevant biomarkers and physiological parameters. This review examines multi-modal biosensing approaches for depression by analyzing electrochemical biosensors for neurotransmitter monitoring alongside wearable sensors tracking autonomic, neural, and behavioral parameters. We explore sensor fusion methodologies, temporal dynamics analysis, and context-aware frameworks that enhance monitoring accuracy through complementary data streams. The review discusses clinical validation across diagnostic, screening, and treatment applications, identifying performance metrics, implementation challenges, and ethical considerations. We outline technical barriers, user acceptance factors, and data privacy concerns while presenting a development roadmap for personalized, continuous monitoring solutions. This integrative approach holds significant potential to revolutionize depression care by enabling earlier detection, precise diagnosis, tailored treatment, and sensitive monitoring guided by objective biosignatures. Successful implementation requires interdisciplinary collaboration among engineers, clinicians, data scientists, and end-users to balance technical sophistication with practical usability across diverse healthcare contexts. Full article

We present a corrosion-resistant quadrupole ion trap mass spectrometer (QIT-MS) designed for trace detection of volatiles in sulfuric acid aerosols, with a specific focus on phosphine (PH₃). Here, we detail the gas calibration methodology using permeation tube technology for generating certified ppb-level PH₃/H₂S/CO₂ mixtures, and report results from mass spectra with sufficient resolution to distinguish isotopic envelopes that validate the detection of PH₃ at a concentration of 62 ppb. Fragmentation patterns for PH₃ and H₂S agree with NIST data, and signal-to-noise performance confirms ppb sensitivity over 2.6 h acquisition periods. We further assess spectral interferences from oxygen isotopes and propose a detection scheme based on isolated phosphorus ions (P⁺) to enable specific and interference-resistant identification of PH₃ and other reduced phosphorus species of astrobiological interest in Venus-like environments. This work extends the capabilities of QIT-MS for trace gas analysis in chemically aggressive atmospheric conditions. Full article

Background: In just twenty years, three dangerous human coronaviruses—SARS-CoV, MERS-CoV, and SARS-CoV-2 have exposed critical gaps in early detection of emerging viral threats. Current diagnostics remain pathogen-focused, often missing the earliest phase of infection. A virus-agnostic, host-based diagnostic capable of detecting responses to viral intrusion is urgently needed. Methods: We hypothesized that the lungs act as biomechanical instruments, with infection altering tissue tension, wave propagation, and flow dynamics in ways detectable through subaudible vibroacoustic signals. In a matched case–control study, we enrolled 19 RT-PCR-confirmed COVID-19 inpatients and 16 matched controls across two Johns Hopkins hospitals. Multimodal data were collected, including passive vibroacoustic auscultation, lung ultrasound, peak expiratory flow, and laboratory markers. Machine learning models were trained to identify host-response biosignatures from anterior chest recordings. Results: 19 COVID-19 inpatients and 16 matched controls (mean BMI 32.4 kg/m², mean age 48.6 years) were successfully enrolled to the study. The top-performing, unoptimized, vibroacoustic-only model achieved an AUC of 0.84 (95% CI: 0.67–0.92). The host-covariate optimized model achieved an AUC of 1.0 (95% CI: 0.94–1.0), with 100% sensitivity (95% CI: 82–100%) and 99.6% specificity (95% CI: 85–100%). Vibroacoustic data from the anterior chest alone reliably distinguished COVID-19 cases from controls. Conclusions: This proof-of-concept study demonstrates that passive, noninvasive vibroacoustic biosignatures can detect host response to viral infection in a hospitalized population and supports further testing of this modality in broader populations. These findings support the development of scalable, host-based diagnostics to enable early, agnostic detection of future pandemic threats (ClinicalTrials.gov number: NCT04556149). Full article

Understanding the mechanisms of protein preservation in extreme environments is essential for identifying potential molecular biosignatures on Mars. In this study, we investigated five sabkha sedimentary samples from the Abu Dhabi coast, spanning from the present day to ~11,000 years before present (BP), to assess how mineralogy and environmental conditions influence long-term protein stability. Using LC-MS/MS and direct Data-independent Acquisition (DIA) proteomic analysis, we identified 722 protein groups and 1300 peptides, revealing a strong correlation between preservation and matrix composition. Carbonate- and silica-rich samples favored the retention of DNA-binding and metal-coordinating proteins via mineral–protein interactions, while halite- and gypsum-dominated facies showed lower recovery due to extreme salinity and reduced biomass input. Functional profiling revealed a shift from metabolic dominance in modern samples to genome maintenance strategies in ancient ones, indicating microbial adaptation to prolonged environmental stress. Contrary to expectations, some ancient samples preserved large, multi-domain proteins, suggesting that early mineral encapsulation can stabilize structurally complex biomolecules over millennial timescales. Taxonomic reconstruction based on preserved proteins showed broad archaeal diversity, including Thaumarchaeota and thermophilic lineages, expanding our understanding of microbial ecology in hypersaline systems. These findings highlight sabkhas as valuable analogs for Martian evaporitic environments and suggest that carbonate–silica matrices on Mars may offer optimal conditions for preserving ancient molecular traces of life. Full article

Transthyretin (TTR) variant (V30M) polyneuropathy (ATTRv-PN) is a progressive systemic amyloidosis caused by transthyretin aggregation, leading to a variety of debilitating manifestations, including neuropathy and cardiomyopathy. We investigated the plasma proteome of heterozygotic V30M TTR asymptomatic carriers and heterozygotic V30M ATTRv-PN patients (before and after tafamidis treatment) versus WT TTR healthy control plasma using an organic solvent-induced shift in solubility assay to identify biosignatures for disease progression and therapeutic response. We identified many proteins, including TTR, apolipoproteins, ceruloplasmin, and proteins with functions in innate immunity that displayed changes in either their abundances or their sensitivity to precipitation. Elevated oxidative modifications of TTR and APOE in ATTRv-PN patients suggest a role for oxidative stress in disease pathogenesis/progression. Tafamidis treatment mitigated these pathology-associated changes, suggesting that alleviating proteotoxic stress impacts these other pathways. Although our study was limited to a Portuguese cohort, these findings nevertheless provide a comprehensive plasma proteomic profile of V30M ATTRv-PN patients, V30M TTR carriers, and tafamidis-treated ATTRv-PN patients over up to 60 months; provide insights into ATTRv-PN pathophysiology; identify potential biomarkers for disease progression and therapeutic response; and highlight the utility of proteomics in advancing personalized treatments for amyloidosis. Full article

We present a corrosion-resistant quadrupole ion trap mass spectrometer (QIT-MS) for the direct detection of biosignature gasses in chemically reactive planetary atmospheres, such as Venusian clouds. The system employs a Paul trap with hyperbolic titanium alloy electrodes and alumina spacers for chemical durability and precise ion confinement. An yttria-coated iridium filament serves as the thermionic emitter within a modular electron gun capable of axial and radial ionization. Analytes are introduced through fused silica capillaries and crescent inlets into a miniature pressure cell. The testbed integrates high-voltage RF electronics, pressure-regulated sample delivery, and FPGA-based control for real-time tuning. Continuous operation in 98% sulfuric acid vapor for over three months demonstrated no degradation in emitter or sensor performance. Mass spectra revealed H₂SO₄ fragmentation and thermally induced decomposition up to 425 K. Spectral variations with filament current and electron energy highlight thermal and electron-induced dissociation dynamics. Operational modes include high-resolution scans and selective ion ejection (e.g., CO₂⁺, N₂⁺) to enhance the detection of PH₃⁺, H₂S⁺, and daughter ions. The compact QIT-MS platform is validated for future missions targeting corrosive atmospheres, enabling in situ astrobiological investigations through the detection of biosignature gasses such as phosphine and hydrogen sulfide. Full article

The Dead Sea is one of the most saline terminal lakes on Earth, and few organisms survive in this harsh environment. In some onshore spring pools, active and diverse microbial communities flourish. In the geological past, microbial-rich environments left their marks in the form of stromatolites. Stromatolites are studied to better understand the appearance of life on Earth and potentially on other planets. Hyperspectral methodologies have been shown to be useful for detecting structures in stromatolites. In an effort to characterize the biosignatures and chemical composition inherent to stromatolites, we created a spectral classification scheme for distinguishing between stromatolites and their bedrock environment—typically carbonatic rocks, mostly dolomites. The overarching aim comprises the development of an automated hyperspectral reflectance method for detecting the presence of stromatolites. We collected and measured 82 field samples with an ASD spectrometer and used our spectral dataset to train three machine learning algorithms (linear regression, K-Nearest Neighbor, XGBoost). The results show the successful detection of stromatolites, with all three prediction methods giving high accuracy rates (stromatolite > 0.9, bedrock dolomite > 0.8). The continuum removal and spectral ratio technique results identified two significant spectral regions, ~1900 nm (water) and ~2310–2320 nm (carbonates), that allow one to differentiate between stromatolites and dolomites. This study establishes the grounds for the automated detection of a fossilized livable environment in a carbonatic terrain based on its hyperspectral reflectance data. The results have significant implications for future mapping efforts and emphasize the feasibility of automated mapping, extending the data acquisition to airborne or satellite-based hyperspectral remote sensing technologies to detect life forms in extreme environments. Full article

The search for life beyond Earth currently hinges on the detection of biosignatures that are indicative of current or past life, with terrestrial life being the sole known example. Deoxyribonucleic acid (DNA), which acts as the long-term storage of genetic information in all known organisms, is considered a biosignature of life. Techniques like the Polymerase Chain Reaction (PCR) are particularly useful as they allow for the amplification of DNA fragments, allowing the detection of even trace amounts of genetic material. This study aimed to detect DNA extracted from colonies of an Antarctic black fungus both when (i) alone and (ii) mixed with a Sulfatic Mars Regolith Simulant (S-MRS), after exposure to increasing doses of Fe ions (up to 1 kGy). PCR-based amplification methods were used for detection. The findings of this study revealed no DNA amplification in samples mixed with Sulfatic Mars Regolith Simulant, providing important insights into the potential application of these techniques for in situ DNA detection during future space exploration missions or for their application on the Mars sample return program; it also gives input in the planetary protection discussions. Full article