Centre de Biophysique Moléculaire

Microfossils reported from Archaean BIFs most likely were liposome-like protocells, which had evolved intracellular mechanisms for energy conservation but not for regulating cell morphology and replication.

Considering the harsh surface conditions on Mars, terrestrial organisms that can survive and remain detectable after exposure to similar conditions provide invaluable models for guiding current and future search-for-life missions. To this end, we evaluated the extremophilic archaeon Acidianus manzaensis grown on ESA01-E Mars analog material as a model organism. We exposed cell-mineral mixtures to one month of desiccation and two weeks of Mars-like conditions in a Mars simulation chamber to evaluate the potential for cell survival after exposure to these conditions. In the search for reliable biomarkers in other planetary environments, such as Mars, molecules that are stable over geological timescales while preserving information indicative of their potential biological origin are crucial. Thiophene-bearing quinones fulfill these requirements, and thiophenes, which are their basic moieties, have been discovered on Mars. Therefore, we analyzed the thiophene-bearing quinone composition of A. manzaensis using mass spectrometry-based metabolomics and discussed potential molecular alterations. Successful re-cultivation after one month of desiccation and two weeks of exposure to Mars-like conditions proved the durability of the organism and its capability for cell recovery after exposure to extreme conditions, paving the way for further investigation.

ABSTRACT The serotonin 5-HT 7 receptor (5-HT 7 R), a member of the rhodopsin-like family of G protein-coupled receptors (GPCRs) is highly expressed in the central nervous system (CNS) and represents a promising target for treating CNS disorders such as sleep disturbances, migraine, neuropsychiatric conditions, and neuropathic pain. Owing to its therapeutic potential, extensive efforts have focused on developing selective 5-HT 7 R ligands. In the last decades, biased signalling has emerged as a key concept in GPCR pharmacology as biased ligands can stabilize specific active states of the receptor and trigger selective activation of downstream signaling pathways. In this context, we recently identified two biased 5-HT 7 R ligands, Serodolin and MOA51, from different chemical series. Here, we aimed to compare the pharmacological and safety profiles of these ligands and to assess their effect on pain-related behaviors and spinal neuroinflammation. In inflammatory pain models (acid acetic writhing, formalin and CFA tests), both serodolin and MOA51 effectively attenuated pain responses to a similar extend. Furthermore, in neuropathic pain models, spinal nerve injury (SNI) and Cuff model, both ligands reversed mechanical allodynia. Interestingly, unlike pregabalin, a clinically used reference drug, neither Serodolin nor MOA51 induced apparent tolerance after 10 consecutive days of administration. Treatment with these 5-HT 7 R ligands also reduced spinal microglial and attenuated neuronal hyperactivity in the spinal cord. Altogether these findings highlight the potential of 5-HT 7 R-biased ligands as promising analgesic candidates capable of modulating neuroinflammatory processes and mitigating both inflammatory and neuropathic pain.

Alcohol use disorder is a psychiatric condition characterized by excessive alcohol consumption. The drugs that are used to treat it often fail to prevent relapse. At the same time, psilocybin is increasingly being investigated for the treatment of various substance use disorder. This review aims to evaluate the results of the most recent clinical trials assessing psilocybin as a treatment for alcohol use disorder. According to these trials, psilocybin seems to reduce craving but its effect on overall alcohol consumption is less clear. There is no doubt that future trials would benefit from larger sample sizes and standardized tests.

Laminae are millimeter-scale features in rocks created by physiochemical processes that can be influenced by the presence and activities of communities of organisms that occur as biofilms and microbial mats. The structure and composition of laminae reflect the processes involved in their formation and can be preserved in the rock record over geologic time; however, diagenetic and metamorphic alteration can lead to the loss of primary information and confusion over the interpretation of their origins. As potential records of ancient life, laminae can preserve evidence of microbial activity over billions of years of Earth's history. On planetary bodies such as Mars, laminae in sedimentary rocks are common and represent significant features of interest that can record habitable conditions (e.g., the presence of liquid water) at the time of their formation. Here we review the significance of laminae as targets for astrobiological exploration. We discuss common mechanisms by which laminae form in natural environments on Earth, present arguments and evidence for laminae as potential biosignatures, and describe how such information is presented in the NASA Life Detection Knowledge Base.

MRI assessment of the tissue redox state is important for revealing and understanding various pathologies, and redox-responsive imaging probes capable of generating discrete and quantifiable signals in both their reduced and oxidized forms can provide enhanced detection reliability. The small fluorinated, redox-active FeL1 chelate is a prototype of such agents. L1 forms stable and inert complexes with both Fe2+ and Fe3+ ions, and the redox potential of the Fe3+L1/Fe2+L1 couple (+240 mV vs NHE) is adapted to biological redox sensing. Fe2+L1 undergoes instantaneous oxidation in the presence of H2O2, and Fe3+L1 is reduced by cysteine, glutathione, and ascorbate. Fe2+L1 and Fe3+L1 have very different proton relaxivities (0.1 mM-1 s-1 and 2.83 mM-1 s-1, respectively, 60 MHz, 298 K), as well as 19F relaxation times (T1 = 71-130 ms; T2 = 60-117 ms and T1 = 2.43 ms; T2 = 1.81 ms, respectively, 400 MHz, 298 K), in accordance with the different paramagnetic relaxation enhancement capacity of the two iron redox states. Upon application of specific MRI pulse sequences adapted to the relaxation rate (RARE for Fe2+L1 and UTE for Fe3+L1, combined with appropriate acquisition parameters), both redox forms are detected in 19F MR phantom images with good sensitivity and signal-to-noise ratios linearly dependent on probe concentration. Fe2+L1 and Fe3+L1 can be readily visualized and unambiguously discriminated based on their 19F relaxation times in living mice, following intramuscular injection. The possibility of monitoring the redox switch in 1H MRI as well is an additional advantage of this bioresponsive probe.

Recent years have seen a swift rise in the use of α-emitting radionuclides such as 225Ac and 223Ra as various radiopharmaceuticals to treat (micro)metastasized tumors. They have shown remarkable effectiveness in clinical practice owing to the highly cytotoxic α-particles that are emitted, which have a very short range in tissue, causing mainly double-stranded DNA breaks. However, it is essential that both chelation and targeting strategies are optimized for their successful translation to clinical application, as α-emitting radionuclides have distinctly different features compared to β--emitters, including their much larger atomic radius. Furthermore, upon α-decay, any daughter nuclide irrevocably breaks free from the targeting molecule, known as the recoil effect, dictating the need for faster targeting to prevent healthy tissue toxicity. In this review we provide a brief overview of the current status of targeted α-therapy and highlight innovations in α-emitter-based chelator design, focusing on the role of click chemistry to allow for fast complexation to biomolecules at mild labeling conditions. Finally, an outlook is provided on different targeting strategies and the role that pre-targeting can play in targeted alpha therapy.