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Abstract Background Interleukin-27 (IL-27) can trigger both pro- and anti-inflammatory responses. This cytokine is elevated in the central nervous system (CNS) of multiple sclerosis (MS) patients, but how it influences neuroinflammatory processes remains unclear. As astrocytes express the receptor for IL-27, we sought to determine how these glial cells respond to this cytokine and whether such exposure alters their interactions with infiltrating activated T lymphocytes. To determine whether inflammation shapes the impact of IL-27, we compared the effects of this cytokine in non-inflamed and inflamed conditions induced by an IL-1β exposure. Main body Transcriptomic analysis of IL-27-exposed human astrocytes showed an upregulation of multiple immune genes. Human astrocytes increased the secretion of chemokines (CXCL9, CXCL10, and CXCL11) and the surface expression of proteins (PD-L1, HLA-E, and ICAM-1) following IL-27 exposure. To assess whether exposure of astrocytes to IL-27 influences the profile of activated T lymphocytes infiltrating the CNS, we used an astrocyte/T lymphocyte co-culture model. Activated human CD4+ or CD8+ T lymphocytes were co-cultured with astrocytes that have been either untreated or pre-exposed to IL‑27 or IL-1β. After 24 h, we analyzed T lymphocytes by flow cytometry for transcription factors and immune molecules. The contact with IL-27-exposed astrocytes increased the percentages of T-bet, Eomes, CD95, IL-18Rα, ICAM-1, and PD-L1 expressing CD4+ and CD8+ T lymphocytes and reduced the proportion of CXCR3-positive CD8+ T lymphocytes. Human CD8+ T lymphocytes co-cultured with human IL-27-treated astrocytes exhibited higher motility than when in contact with untreated astrocytes. These results suggested a preponderance of kinapse-like over synapse-like interactions between CD8+ T lymphocytes and IL-27-treated astrocytes. Finally, CD8+ T lymphocytes from MS patients showed higher motility in contact with IL-27-exposed astrocytes compared to healthy donors’ cells. Conclusion Our results establish that IL-27 alters the immune functions of human astrocytes and shapes the profile and motility of encountered T lymphocytes, especially CD8+ T lymphocytes from MS patients.

In recent years, metal hydride research has become one of the driving forces of the high-pressure community, as it is believed to hold the key to superconductivity close to ambient temperature. While numerous novel metal hydride compounds have been reported and extensively investigated for their superconducting properties, little attention has been focused on the atomic and electronic states of hydrogen, the main ingredient in these novel compounds. Here, we present combined 1H- and 139La-NMR data on lanthanum superhydrides, LaHx, (x = 10.2 − 11.1), synthesized after laser heating at pressures above 160 GPa. Strikingly, we found hydrogen to be in a highly diffusive state at room temperature, with diffusion coefficients in the order of 10−6cm2s−1. We found that this diffusive state of hydrogen results in a dynamic de-hydrogenation of the sample over the course of several weeks, approaching a composition similar to its precursor materials. Quantitative measurements demonstrate that the synthesized superhydrides continuously decompose over time. Transport measurements underline this conclusion as superconducting critical temperatures were found to decrease significantly over time as well. This observation sheds new light on formerly unanswered questions on the long-term stability of metal superhydrides. The authors present nuclear magnetic resonance data on lanthanum superhydrides (LaHx) under high pressure. They find that the hydrogen is in a highly diffusive state which results in a dynamic de-hydrogenation of the sample on a time scale of weeks. [ABSTRACT FROM AUTHOR]

The role nematicity and magnetic fluctuations play in the manifestation of unconventional superconductivity for Fe-based superconductors is actively debated with, so far, no clear consensus. Here, the authors study the resistive properties of sulfur-doped FeSe under applied pressure finding evidence of two distinct contributions to the electrical resistivity, which suggest a decoupling of nematic and magnetic fluctuations in this system.

The charge-density-wave (CDW) amplitude mode of the high-pressure sulfur-IV phase is observed between 83 and 146 GPa using Raman spectroscopy. The energy of this excitation softens with pressure yet remains finite at ν_{CDW}>100cm^{−1} up to the critical pressure, which is indicative of a weakly first-order transition. Our ab initio calculations show that the finite energy of the excitation originates from the coupling and mutual stabilization of the CDW modulation and a monoclinic lattice distortion. At the critical pressure, both the CDW modulation and lattice distortion disappear simultaneously. Due to the prevalence of CDW phases, this coupling between the CDW modulation and lattice distortion is expected to be relevant for a wide variety of elements and compounds.

Electron-phonon interaction is essential for understanding electronic and optical properties of lead halide perovskites. Here, using multiphonon Raman scattering and THz time-domain spectroscopy, the authors characterize the full phonon spectrum of CsPbBr3 and identify a single phonon mode that dominates electron-phonon scattering.

Multiple sclerosis (MS) is characterized by the loss of myelin and of myelin-producing oligodendrocytes (OLs) in the central nervous system (CNS). Pro-inflammatory CD4+ Th17 cells are considered pathogenic in MS and are harmful to OLs. We investigated the mechanisms driving human CD4+ T cell-mediated OL cell death. Using fluorescent and brightfield in vitro live imaging, we found that compared to Th2-polarized cells, Th17-polarized cells show greater interactions with primary human OLs and human oligodendrocytic cell line MO3.13, displaying longer duration of contact, lower mean speed, and higher rate of vesicle-like structure formation at the sites of contact. Using single-cell RNA sequencing, we assessed the transcriptomic profile of primary human OLs and Th17-polarized cells in direct contact or separated by an insert. We showed that upon close interaction, OLs upregulate the expression of mRNA coding for chemokines and antioxidant/anti-apoptotic molecules, while Th17-polarized cells upregulate the expression of mRNA coding for chemokines and pro-inflammatory cytokines such as IL-17A, IFN-γ, and granzyme B. We found that secretion of CCL3, CXCL10, IFN-γ, TNFα, and granzyme B is induced upon direct contact in cocultures of human Th17-polarized cells with human OLs. In addition, we validated by flow cytometry and immunofluorescence that granzyme B levels are upregulated in Th17-polarized compared to Th2-polarized cells and are even higher in Th17-polarized cells upon direct contact with OLs or MO3.13 cells compared to Th17-polarized cells separated from OLs by an insert. Moreover, granzyme B is detected in OLs and MO3.13 cells following direct contact with Th17-polarized cells, suggesting the release of granzyme B from Th17-polarized cells into OLs/MO3.13 cells. To confirm granzyme B–mediated cytotoxicity toward OLs, we showed that recombinant human granzyme B can induce OLs and MO3.13 cell death. Furthermore, pretreatment of Th17-polarized cells with a reversible granzyme B blocker (Ac-IEPD-CHO) or a natural granzyme B blocker (serpina3N) improved survival of MO3.13 cells upon coculture with Th17 cells. In conclusion, we showed that human Th17-polarized cells form biologically significant contacts with human OLs and exert direct toxicity by releasing granzyme B.

Today, there is a rapidly growing demand for sensitive and selective biosensors in various domains, including environmental monitoring such as (waste)water control, detection of pollution for personal/public safety, agricultural/food safety and quality control, veterinary and medical diagnostics, etc [...]

Chronic inflammation is associated with higher risk of cardiovascular disease (CVD) in people living with HIV (PLWH). We have previously shown that interleukin-32 (IL-32), a multi-isoform proinflammatory cytokine, is chronically upregulated in PLWH and is linked with CVD. However, the mechanistic roles of the different IL-32 isoforms in CVD are yet to be identified. In this study, we aimed to investigate the potential impact of IL-32 isoforms on coronary artery endothelial cells (CAEC), whose dysfunction represents a major factor for atherosclerosis. Our results demonstrated that the predominantly expressed IL-32 isoforms (IL-32β and IL-32γ) have a selective impact on the production of the proinflammatory cytokine IL-6 by CAEC. Furthermore, these two isoforms induced endothelial cell dysfunction by upregulating the expression of the adhesion molecules ICAM-I and VCAM-I and the chemoattractants CCL-2, CXCL-8 and CXCL-1. IL-32-mediated expression of these chemokines was sufficient to drive monocyte transmigration in vitro. Finally, we demonstrate that IL-32 expression in both PLWH and controls correlates with the carotid artery stiffness, measured by the cumulated lateral translation. These results suggest a role for IL-32-mediated endothelial cell dysfunction in dysregulation of the blood vessel wall and that IL-32 may represent a therapeutic target to prevent CVD in PLWH.

Foodborne pathogens present a serious issue around the world due to the remarkably high number of illnesses they cause every year. In an effort to narrow the gap between monitoring needs and currently implemented classical detection methodologies, the last decades have seen an increased development of highly accurate and reliable biosensors. Peptides as recognition biomolecules have been explored to develop biosensors that combine simple sample preparation and enhanced detection of bacterial pathogens in food. This review first focuses on the selection strategies for the design and screening of sensitive peptide bioreceptors, such as the isolation of natural antimicrobial peptides (AMPs) from living organisms, the screening of peptides by phage display and the use of in silico tools. Subsequently, an overview on the state-of-the-art techniques in the development of peptide-based biosensors for foodborne pathogen detection based on various transduction systems was given. Additionally, limitations in classical detection strategies have led to the development of innovative approaches for food monitoring, such as electronic noses, as promising alternatives. The use of peptide receptors in electronic noses is a growing field and the recent advances of such systems for foodborne pathogen detection are presented. All these biosensors and electronic noses are promising alternatives for the pathogen detection with high sensitivity, low cost and rapid response, and some of them are potential portable devices for on-site analyses.

Loss of muscle mass and function induced by sepsis contributes to physical inactivity and disability in intensive care unit patients. Limiting skeletal muscle deconditioning may thus be helpful in reducing the long‐term effect of muscle wasting in patients. We tested the hypothesis that invalidation of the myostatin gene, which encodes a powerful negative regulator of skeletal muscle mass, could prevent or attenuate skeletal muscle wasting and improve survival of septic mice. Sepsis was induced by caecal ligature and puncture (CLP) in 13‐week‐old C57BL/6J wild‐type and myostatin knock‐out male mice. Survival rates were similar in wild‐type and myostatin knock‐out mice seven days after CLP. Loss in muscle mass was also similar in wild‐type and myostatin knock‐out mice 4 and 7 days after CLP. The loss in muscle mass was molecularly supported by an increase in the transcript level of E3‐ubiquitin ligases and autophagy–lysosome markers. This transcriptional response was blunted in myostatin knock‐out mice. No change was observed in the protein level of markers of the anabolic insulin/IGF1‐Akt‐mTOR pathway. Muscle strength was similarly decreased in wild‐type and myostatin knock‐out mice 4 and 7 days after CLP. This was associated with a modified expression of genes involved in ion homeostasis and excitation–contraction coupling, suggesting that a long‐term functional recovery following experimental sepsis may be impaired by a dysregulated expression of molecular determinants of ion homeostasis and excitation–contraction coupling. In conclusion, myostatin gene invalidation does not provide any benefit in preventing skeletal muscle mass loss and strength in response to experimental sepsis. Key points: Survival rates are similar in wild‐type and myostatin knock‐out mice seven days after the induction of sepsis.Loss in muscle mass and muscle strength are similar in wild‐type and myostatin knock‐out mice 4 and 7 days after the induction of an experimental sepsis.Despite evidence of a transcriptional regulation, the protein level of markers of the anabolic insulin/IGF1‐Akt‐mTOR pathway remained unchanged.RT‐qPCR analysis of autophagy–lysosome pathway markers indicates that activity of the pathway may be altered by experimental sepsis in wild‐type and myostatin knock‐out mice.Experimental sepsis induces greater variations in the mRNA levels of wild‐type mice than those of myostatin knock‐out mice, without providing any significant catabolic resistance or functional benefits. [ABSTRACT FROM AUTHOR]

In September 2023, the two largest bioimaging networks in the Americas, Latin America Bioimaging (LABI) and BioImaging North America (BINA), came together during a 1‐week meeting in Mexico. This meeting provided opportunities for participants to interact closely with decision‐makers from imaging core facilities across the Americas. The meeting was held in a hybrid format and attended in‐person by imaging scientists from across the Americas, including Canada, the United States, Mexico, Colombia, Peru, Argentina, Chile, Brazil and Uruguay. The aims of the meeting were to discuss progress achieved over the past year, to foster networking and collaborative efforts among members of both communities, to bring together key members of the international imaging community to promote the exchange of experience and expertise, to engage with industry partners, and to establish future directions within each individual network, as well as common goals. This meeting report summarises the discussions exchanged, the achievements shared, and the goals set during the LABIxBINA2023: Bioimaging across the Americas meeting. [ABSTRACT FROM AUTHOR]

To fully perform their functions, T lymphocytes migrate within organs’ parenchyma and interact with local cells. Infiltration of T lymphocytes within the central nervous system (CNS) is associated with numerous neurodegenerative disorders. Nevertheless, how these immune cells communicate and respond to neural cells remains unresolved. To investigate the behavior of T lymphocytes that reach the CNS, we have established an in vitro co-culture model and analyzed the spatiotemporal interactions between human activated CD8+ T lymphocytes and primary human astrocytes and neurons using time-lapse microscopy. By combining multiple variables extracted from individual CD8+ T cell tracking, we show that CD8+ T lymphocytes adopt a more motile and exploratory behavior upon interacting with astrocytes than with neurons. Pretreatment of astrocytes or neurons with IL-1β to mimic in vivo inflammation significantly increases CD8+ T lymphocyte motility. Using visual interpretation and analysis of numerical variables extracted from CD8+ T cell tracking, we identified four distinct CD8+ T lymphocyte behaviors: scanning, dancing, poking and round. IL-1β-pretreatment significantly increases the proportion of scanning CD8+ T lymphocytes, which are characterized by active exploration, and reduces the proportion of round CD8+ T lymphocytes, which are less active. Blocking MHC class I on astrocytes significantly diminishes the proportion of poking CD8+ T lymphocytes, which exhibit synapse-like interactions. Lastly, our co-culture time-lapse model is easily adaptable and sufficiently sensitive and powerful to characterize and quantify spatiotemporal interactions between human T lymphocytes and primary human cells in different conditions while preserving viability of fragile cells such as neurons and astrocytes.

Author(s): S. Licciardello [sup.1] , J. Buhot [sup.1] , J. Lu [sup.1] , J. Ayres [sup.1] [sup.2] , S. Kasahara [sup.3] , Y. Matsuda [sup.3] , T. Shibauchi [sup.4] , [...], Correlated electron systems are highly susceptible to various forms of electronic order. By tuning the transition temperature towards absolute zero, striking deviations from conventional metallic (Fermi-liquid) behaviour can be realized. Evidence for electronic nematicity, a correlated electronic state with broken rotational symmetry, has been reported in a host of metallic systems.sup.1-5 that exhibit this so-called quantum critical behaviour. In all cases, however, the nematicity is found to be intertwined with other forms of order, such as antiferromagnetism.sup.5-7 or charge-density-wave order.sup.8, that might themselves be responsible for the observed behaviour. The iron chalcogenide FeSe.sub.1-xS.sub.x is unique in this respect because its nematic order appears to exist in isolation.sup.9-11, although until now, the impact of nematicity on the electronic ground state has been obscured by superconductivity. Here we use high magnetic fields to destroy the superconducting state in FeSe.sub.1-xS.sub.x and follow the evolution of the electrical resistivity across the nematic quantum critical point. Classic signatures of quantum criticality are revealed: an enhancement in the coefficient of the T.sup.2 resistivity (due to electron-electron scattering) on approaching the critical point and, at the critical point itself, a strictly T-linear resistivity that extends over a decade in temperature T. In addition to revealing the phenomenon of nematic quantum criticality, the observation of T-linear resistivity at a nematic critical point also raises the question of whether strong nematic fluctuations play a part in the transport properties of other 'strange metals', in which T-linear resistivity is observed over an extended regime in their respective phase diagrams. The pattern of electrical resistivity in an unconventional superconductor at high magnetic fields and low temperatures across the nematic quantum critical point reveals two classic signatures of quantum criticality.

Loop-mediated isothermal amplification (LAMP) is an exponential amplification method of DNA strands that is more and more used for its high performances. Thanks to its high sensitivity and selectivity, LAMP found numerous applications from the detection of pathogens or viruses through their genome amplification to its incorporation as an amplification strategy in protein or miRNA biomarker quantification. The LAMP method is composed of two stages: the first one consists in the transformation of the DNA strands into dumbbell structures formed of two stems and loops thanks to four primers; then, in the second stage, only two primers are required to amplify the dumbbells exponentially in numerous hairpins of increasing lengths. In this paper, we propose a theoretical framework to analyze the kinetics of the second stage of LAMP, the isothermal dumbbell exponential amplification (IDEA) as function of the physico-chemical parameters of the amplification reaction. Dedicated experiments validate the models. We believe these results may help the optimization of LAMP performances by reducing the number of experiments necessary to find the best parameters.

The last three decades have witnessed an increasing demand for novel analytical tools for the analysis of gases including odorants and volatile organic compounds (VOCs) in various domains. Traditional techniques such as gas chromatography coupled with mass spectrometry, although very efficient, present several drawbacks. Such a context has incited the research and industrial communities to work on the development of alternative technologies such as artificial olfaction systems, including gas sensors, olfactory biosensors and electronic noses (eNs). A wide variety of these systems have been designed using chemiresistive, electrochemical, acoustic or optical transducers. Among optical transduction systems, surface plasmon resonance (SPR) has been extensively studied thanks to its attractive features (high sensitivity, label free, real-time measurements). In this paper, we present an overview of the advances in the development of artificial olfaction systems with a focus on their development based on propagating SPR with different coupling configurations, including prism coupler, wave guide, and grating.

Small molecules are ubiquitous in nature and their detection is relevant in various domains. However, due to their size, sensitive and selective probes are difficult to select and the detection methods are generally indirect. In this study, we introduced the use of melting curve analysis of aptachains based on split-aptamers for the detection of adenosine. Aptamers, short oligonucleotides, are known to be particularly efficient probes compared to antibodies thanks to their advantageous probe/target size ratio. Aptachains are formed from dimers with dangling ends followed by the split-aptamer binding triggered by the presence of the target. The high melting temperature of the dimers served as a calibration for the detection/quantification of the target based on the height and/or temperature shift of the aptachain melting peak.

In the 90s, the development of a novel single molecule technique based on nanopore sensing emerged. Preliminary improvements were based on the molecular or biological engineering of protein nanopores along with the use of nanotechnologies developed in the context of microelectronics. Since the last decade, the convergence between those two worlds has allowed for biomimetic approaches. In this respect, the combination of nanopores with aptamers, single-stranded oligonucleotides specifically selected towards molecular or cellular targets from an in vitro method, gained a lot of interest with potential applications for the single molecule detection and recognition in various domains like health, environment or security. The recent developments performed by combining nanopores and aptamers are highlighted in this review and some perspectives are drawn.

Artificial noses are broad-spectrum multisensors dedicated to the detection of volatile organic compounds (VOCs). Despite great recent progress, they still suffer from a lack of sensitivity and selectivity. We will review, in a systemic way, the biomimetic strategies for improving these performance criteria, including the design of sensing materials, their immobilization on the sensing surface, the sampling of VOCs, the choice of a transduction method, and the data processing. This reflection could help address new applications in domains where high-performance artificial noses are required such as public security and safety, environment, industry, or healthcare.

Ionizing radiations induce clustered damage sites known to be severely challenging for the cell's repair machinery. In the present study, we have grafted on a biochip four synthetic oligonucleotide duplexes containing either a single 8-oxoguanine, a single 2'-deoxyribose abasic site or two different clustered damages containing these two lesions on opposite strands. Using a SPR imaging-based DNA array, we qualitatively observed the hierarchy of lesion processing by the base excision repair (BER) enzyme Fpg (Formamidopyrimidine (fapy)-DNA glycosylase). We could notably show that Fpg can convert a cluster of lesions into a potentially lethal double strand break (DSB) and demonstrate that SPR imaging is suitable to investigate the incision steps occurring during the repair process.

This study explores how French-secondary-trainee teachers perceive their professional development over their year-long training. Two research questions are addressed: How prominent is workplace learning in teaching competencies acquisition? Is there a relationship between learning modes and the kind of teaching competencies to be acquired? Four hundred and seventy-three secondary-trainee teachers were asked to complete a questionnaire in which they rated to what extent 28 teaching competencies were being acquired at the end of the one-year training, along with the learning mode of these competencies. The findings suggest that learning on workplace is a multifaceted process that cannot be curtailed to mentoring.

The development of sensitive methods for in situ detection of biomarkers is a real challenge to bring medical diagnosis a step forward. The proof-of-concept of a remote multiplexed biomolecular interaction detection through a plasmonic optical fiber bundle is demonstrated here. The strategy relies on a fiber optic biosensor designed from a 300 µm diameter bundle composed of 6000 individual optical fibers. When appropriately etched and metallized, each optical fiber exhibits specific plasmonic properties. The surface plasmon resonance phenomenon occurring at the surface of each fiber enables to measure biomolecular interactions, through the changes of the retro-reflected light intensity due to light/plasmon coupling variations. The functionalization of the microstructured bundle by multiple protein probes was performed using new polymeric 3D-printed microcantilevers. Such soft cantilevers allow for immobilizing the probes in micro spots, without damaging the optical microstructures nor the gold layer. We show here the potential of this device to perform the multiplexed detection of two different antibodies with limits of detection down to a few tenths of nanomoles per liter. This tool, adapted for multiparametric, real-time, and label free monitoring is minimally invasive and could then provide a useful platform for in vivo targeted molecular analysis.

This review summarizes recent advances in micro- and nanopore technologies with a focus on the functionalization of pores using a promising method named contactless electro-functionalization (CLEF). CLEF enables the localized grafting of electroactive entities onto the inner wall of a micro- or nano-sized pore in a solid-state silicon/silicon oxide membrane. A voltage or electrical current applied across the pore induces the surface functionalization by electroactive entities exclusively on the inside pore wall, which is a significant improvement over existing methods. CLEF’s mechanism is based on the polarization of a sandwich-like silicon/silicon oxide membrane, creating electronic pathways between the core silicon and the electrolyte. Correlation between numerical simulations and experiments have validated this hypothesis. CLEF-induced micro- and nanopores functionalized with antibodies or oligonucleotides were successfully used for the detection and identification of cells and are promising sensitive biosensors. This technology could soon be successfully applied to planar configurations of pores, such as restrictions in microfluidic channels.

The recent discovery of a nonmagnetic nematic quantum critical point (QCP) in the iron chalcogenide family FeSe_{1-x}S_{x} has raised the prospect of investigating, in isolation, the role of nematicity on the electronic properties of correlated metals. Here we report a detailed study of the normal state transverse magnetoresistance (MR) in FeSe_{1-x}S_{x} for a series of S concentrations spanning the nematic QCP. For all temperatures and x values studied, the MR can be decomposed into two distinct components: one that varies quadratically in magnetic field strength μ_{0}H and one that follows precisely the quadrature scaling form recently reported in metals at or close to a QCP and characterized by a H-linear MR over an extended field range. The two components evolve systematically with both temperature and S substitution in a manner that is determined by their proximity to the nematic QCP. This study thus reveals the coexistence of two independent charge sectors in a quantum critical system. Moreover, the quantum critical component of the MR is found to be less sensitive to disorder than the quadratic (orbital) MR, suggesting that detection of the latter in previous MR studies of metals near a QCP may have been obscured.

We investigated the spatio-temporal dynamics of learning-induced cAMP response element-binding protein activation/phosphorylation (pCREB) in mice trained in a spatial reference memory task in the water maze. Using immunohistochemistry, we examined pCREB immunoreactivity (pCREB-ir) in hippocampal CA1 and CA3 and related brain structures. During the course of spatial learning over Days 1-9, pCREB-ir progressively increased in hippocampal neurons whereas its level in the dorsal striatum decreased. No significant changes were observed in the prelimbic cortex and lateral amygdala. Mice killed at various time points after the last training session demonstrated two waves of pCREB-ir in CA1 and an early transient CREB phosphorylation in area CA3, lateral amygdala, and prelimbic cortex. We show that CREB phosphorylation and downstream gene Zif268 activation remained sustained in CA1 and CA3 for at least 24 h after extended training (Days 8-9) but not during early training (Day 3). The present results indicate that the strong CA1 CREB phosphorylation observed immediately after training was not related strictly to learning or to memory. In contrast, at 15 min after training, the changes in CA1 CREB phosphorylation state were specifically related to individual learning capability. We suggest that hippocampal-learning specificity of CREB is reflected best by duration, rather than magnitude, of CREB phosphorylation. (Contains 1 footnote.)