Healthy Aging Delays Scalp EEG Sensitivity to Noise in a Face Discrimination Task

We used a single-trial ERP approach to quantify age-related changes in the time-course of noise sensitivity. A total of 62 healthy adults, aged between 19 and 98, performed a non-speeded discrimination task between two faces. Stimulus information was controlled by parametrically manipulating the phase spectrum of these faces. Behavioral 75% correct thresholds increased with age. This result may be explained by lower signal-to-noise ratios in older brains. ERP from each subject were entered into a single-trial general linear regression model to identify variations in neural activity statistically associated with changes in image structure. The fit of the model, indexed by R2, was computed at multiple post-stimulus time points. The time-course of the R2 function showed significantly delayed noise sensitivity in older observers. This age effect is reliable, as demonstrated by test–retest in 24 subjects, and started about 120 ms after stimulus onset. Our analyses suggest also a qualitative change from a young to an older pattern of brain activity at around 47 ± 4 years old

Mitochondrial cyclophilin D promotes disease tolerance by licensing NK cell development and IL-22 production against influenza virus

Severity of pulmonary viral infections, including influenza A virus (IAV), is linked to excessive immunopathology, which impairs lung function. Thus, the same immune responses that limit viral replication can concomitantly cause lung damage that must be countered by largely uncharacterized disease tolerance mechanisms. Here, we show that mitochondrial cyclophilin D (CypD) protects against IAV via disease tolerance. Cyp

Parametric study of EEG sensitivity to phase noise during face processing

<b>Background: </b> The present paper examines the visual processing speed of complex objects, here faces, by mapping the relationship between object physical properties and single-trial brain responses. Measuring visual processing speed is challenging because uncontrolled physical differences that co-vary with object categories might affect brain measurements, thus biasing our speed estimates. Recently, we demonstrated that early event-related potential (ERP) differences between faces and objects are preserved even when images differ only in phase information, and amplitude spectra are equated across image categories. Here, we use a parametric design to study how early ERP to faces are shaped by phase information. Subjects performed a two-alternative force choice discrimination between two faces (Experiment 1) or textures (two control experiments). All stimuli had the same amplitude spectrum and were presented at 11 phase noise levels, varying from 0% to 100% in 10% increments, using a linear phase interpolation technique. Single-trial ERP data from each subject were analysed using a multiple linear regression model. <b>Results: </b> Our results show that sensitivity to phase noise in faces emerges progressively in a short time window between the P1 and the N170 ERP visual components. The sensitivity to phase noise starts at about 120–130 ms after stimulus onset and continues for another 25–40 ms. This result was robust both within and across subjects. A control experiment using pink noise textures, which had the same second-order statistics as the faces used in Experiment 1, demonstrated that the sensitivity to phase noise observed for faces cannot be explained by the presence of global image structure alone. A second control experiment used wavelet textures that were matched to the face stimuli in terms of second- and higher-order image statistics. Results from this experiment suggest that higher-order statistics of faces are necessary but not sufficient to obtain the sensitivity to phase noise function observed in response to faces. <b>Conclusion: </b> Our results constitute the first quantitative assessment of the time course of phase information processing by the human visual brain. We interpret our results in a framework that focuses on image statistics and single-trial analyses

M. tuberculosis Reprograms Hematopoietic Stem Cells to Limit Myelopoiesis and Impair Trained Immunity

A greater understanding of hematopoietic stem cell (HSC) regulation is required for dissecting protective versus detrimental immunity to pathogens that cause chronic infections such as Mycobacterium tuberculosis (Mtb). We have shown that systemic administration of Bacille Calmette-Guérin (BCG) or ß-glucan reprograms HSCs in the bone marrow (BM) via a type II interferon (IFN-II) or interleukin-1 (IL1) response, respectively, which confers protective trained immunity against Mtb. Here, we demonstrate that, unlike BCG or ß-glucan, Mtb reprograms HSCs via an IFN-I response that suppresses myelopoiesis and impairs development of protective trained immunity to Mtb. Mechanistically, IFN-I signaling dysregulates iron metabolism, depolarizes mitochondrial membrane potential, and induces cell death specifically in myeloid progenitors. Additionally, activation of the IFN-I/iron axis in HSCs impairs trained immunity to Mtb infection. These results identify an unanticipated immune evasion strategy of Mtb in the BM that controls the magnitude and intrinsic anti-microbial capacity of innate immunity to infection

Human alveolar macrophage metabolism is compromised during Mycobacterium tuberculosis infection

Pulmonary macrophages have two distinct ontogenies: long-lived embryonically-seeded alveolar macrophages (AM) and bone marrow-derived macrophages (BMDM). Here, we show that after infection with a virulent strain of Mycobacterium tuberculosis (H37Rv), primary murine AM exhibit a unique transcriptomic signature characterized by metabolic reprogramming distinct from conventional BMDM. In contrast to BMDM, AM failed to shift from oxidative phosphorylation (OXPHOS) to glycolysis and consequently were unable to control infection with an avirulent strain (H37Ra). Importantly, healthy human AM infected with H37Ra equally demonstrated diminished energetics, recapitulating our observation in the murine model system. However, the results from seahorse showed that the shift towards glycolysis in both AM and BMDM was inhibited by H37Rv. We further demonstrated that pharmacological (e.g. metformin or the iron chelator desferrioxamine) reprogramming of AM towards glycolysis reduced necrosis and enhanced AM capacity to control H37Rv growth. Together, our results indicate that the unique bioenergetics of AM renders these cells a perfect target for Mtb survival and that metabolic reprogramming may be a viable host targeted therapy against TB

Reconfigurable photon localization by coherent drive and dissipation in photonic lattices

7 pags., 4 figs.The engineering of localized modes in photonic structures is one of the main targets of modern photonics. An efficient strategy to design these modes is to use the interplay of constructive and destructive interference in periodic photonic lattices. This mechanism is at the origin of the defect modes in photonic bandgaps, bound states in the continuum, and compact localized states in flat bands. Here, we show that in lattices of lossy resonators, the addition of external optical drives with a controlled phase enlarges the possibilities of manipulating interference effects and allows for the design of novel types of localized modes. Using a honeycomb lattice of coupled micropillars resonantly driven with several laser spots at energies within its photonic bands, we demonstrate the localization of light in at-will geometries down to a single site. These localized modes are fully reconfigurable and have the potentiality of enhancing nonlinear effects and of controlling light-matter interactions with single site resolution.Ministerio de Ciencia, Innovación y Universidades (PGC2018-094792-B-100); Consejo Superior de Investigaciones Científicas (PTI-001); Comunidad de Madrid (CAM 2020 Y2020/TCS-6545); Narodowe Centrum Nauki (DEC-2019/32/T/ST3/00332); Agence Nationale de la Recherche (ANR-11-LABX-0007, ANR-16-CE30-0021, ANR-16-IDEX-0004 ULNE, ANR-QUAN-0003-05); European Research Council (820392, 865151, 949730), Région Hauts-de-France

Topological gap solitons in a 1D non-Hermitian lattice

Nonlinear topological photonics is an emerging field aiming at extending the fascinating properties of topological states to the realm where interactions between the system constituents cannot be neglected. Interactions can indeed trigger topological phase transitions, induce symmetry protection and robustness properties for the many-body system. Moreover when coupling to the environment via drive and dissipation is also considered, novel collective phenomena are expected to emerge. Here, we report the nonlinear response of a polariton lattice implementing a non-Hermitian version of the Su-Schrieffer-Heeger model. We trigger the formation of solitons in the topological gap of the band structure, and show that these solitons demonstrate robust nonlinear properties with respect to defects, because of the underlying sub-lattice symmetry. Leveraging on the system non-Hermiticity, we engineer the drive phase pattern and unveil bulk solitons that have no counterpart in conservative systems. They are localized on a single sub-lattice with a spatial profile alike a topological edge state. Our results demonstrate a tool to stabilize the nonlinear response of driven dissipative topological systems, which may constitute a powerful resource for nonlinear topological photonics

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response