IST Austria: PubRep (Institute of Science and Technology)
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Microglia determine an immune-challenged environment and facilitate ibuprofen action in human retinal organoids
No full textPrenatal immune challenges pose significant risks to human embryonic brain and eye development. However, our knowledge about the safe usage of anti-inflammatory drugs during pregnancy is still limited. While human induced pluripotent stem cells (hIPSC)-derived brain organoid models have started to explore functional consequences upon viral stimulation, these models commonly lack microglia, which are susceptible to and promote inflammation. Furthermore, microglia are actively involved in neuronal development. Here, we generate hIPSC-derived microglia precursor cells and assemble them into retinal organoids. Once the outer plexiform layer forms, these hIPSC-derived microglia (iMG) fully integrate into the retinal organoids. Since the ganglion cell survival declines by this time in 3D-retinal organoids, we adapted the model into 2D and identify that the improved ganglion cell number significantly decreases only with iMG presence. In parallel, we applied the immunostimulant POLY(I:C) to mimic a fetal viral infection. While POLY(I:C) exposure alters the iMG phenotype, it does not hinder their interaction with ganglion cells. Furthermore, iMG significantly enhance the supernatant’s inflammatory secretome and increase retinal cell proliferation. Simultaneous exposure with the non-steroidal anti-inflammatory drug (NSAID) ibuprofen dampens POLY(I:C)-mediated changes of the iMG phenotype and ameliorates cell proliferation. Remarkably, while POLY(I:C) disrupts neuronal calcium dynamics independent of iMG, ibuprofen rescues this effect only if iMG are present. Mechanistically, ibuprofen targets the enzymes cyclooxygenase 1 and 2 (COX1/PTGS1 and COX2/PTGS2) simultaneously, from which iMG mainly express COX1. Selective COX1 blockage fails to restore the calcium peak amplitude upon POLY(I:C) stimulation, suggesting ibuprofen’s beneficial effect depends on the presence and interplay of COX1 and COX2. These findings underscore the importance of microglia in the context of prenatal immune challenges and provide insight into the mechanisms by which ibuprofen exerts its protective effects during embryonic development
Privacy for free in the overparameterized regime
No full textDifferentially private gradient descent (DP-GD) is a popular algorithm to train deep learning models with provable guarantees on the privacy of the training data. In the last decade, the problem of understanding its performance cost with respect to standard GD has received remarkable attention from the research community, which formally derived upper bounds on the excess population risk RP in different learning settings. However, existing bounds typically degrade with over-parameterization, i.e., as the number of parameters p gets larger than the number of training samples n -- a regime which is ubiquitous in current deep-learning practice. As a result, the lack of theoretical insights leaves practitioners without clear guidance, leading some to reduce the effective number of trainable parameters to improve performance, while others use larger models to achieve better results through scale. In this work, we show that in the popular random features model with quadratic loss, for any sufficiently large p , privacy can be obtained for free, i.e., |RP|=o(1) , not only when the privacy parameter ε has constant order, but also in the strongly private setting ε=o(1) . This challenges the common wisdom that over-parameterization inherently hinders performance in private learning
Quantum many-body scars beyond the PXP model in Rydberg simulators
No full textPersistent revivals recently observed in Rydberg atom simulators have challenged our understanding of thermalization and attracted much interest to the concept of quantum many-body scars (QMBSs). QMBSs are non-thermal highly excited eigenstates that coexist with typical eigenstates in the spectrum of many-body Hamiltonians, and have since been reported in multiple theoretical models, including the so-called PXP model, approximately realized by Rydberg simulators. At the same time, questions of how common QMBSs are and in what models they are physically realized remain open. In this Letter, we demonstrate that QMBSs exist in a broader family of models that includes and generalizes PXP to longer-range constraints and states with different periodicity. We show that in each model, multiple QMBS families can be found. Each of them relies on a different approximate algebra, leading to oscillatory dynamics in all cases. However, in contrast to the PXP model, their observation requires launching dynamics from weakly entangled initial states rather than from a product state. QMBSs reported here may be experimentally probed using Rydberg atom simulator in the regime of longer-range Rydberg blockades
Superconducting proximity effect in two-dimensional hole gases
No full textTechnology involving hybrid superconductor–semiconductor materials is a promising avenue for engineering quantum devices for information storage, manipulation, and transmission. Proximity-induced superconducting correlations are an essential part of such devices. While the proximity effect in the conduction band of common semiconductors is well understood, its manifestation in confined hole gases, realized for instance in germanium, is an active area of research. Lower-dimensional hole-based systems, particularly in germanium, are emerging as an attractive platform for a variety of solid-state quantum devices, due to their combination of efficient spin and charge control and long coherence times. The recent experimental realization of the proximity effect in germanium thus calls for a theoretical description that is tailored to hole gases. In this work, we propose a simple model to describe proximity-induced superconductivity in two-dimensional hole gases, incorporating both the heavy-hole (HH) and light-hole (LH) bands. We start from the Luttinger–Kohn model, introduce three parameters that characterize hopping across the superconductor–semiconductor interface, and derive explicit intraband and interband effective pairing terms for the HH and LH bands. Unlike previous approaches, our theory provides a quantitative relationship between induced pairings and interface properties. Restricting our general model to an experimentally relevant case where only the HH band crosses the chemical potential, we predict the coexistence of -wave and -wave singlet pairings, along with triplet-type pairings, and modified Zeeman and Rashba spin–orbit couplings. Our results thus present a starting point for theoretical modeling of quantum devices based on proximitized hole gases, fueling further progress in quantum technology
A bacterial toxin-antitoxin system as a native defence element against RNA phages
No full textBacteria have evolved a wide range of defence strategies to protect themselves against bacterial viruses (phages). Most known bacterial antiphage defence systems target phages with DNA genomes, which raises the question of how bacteria defend against phages with RNA genomes. Bacterial toxin–antitoxin systems that cleave intracellular RNA could potentially protect bacteria against RNA phages, but this has not been explored experimentally. In this study, we investigated the role of a model toxin–antitoxin system, MazEF, in protecting Escherichia coli against two RNA phage species. When challenged with these phages, the native presence of mazEF moderately reduced population susceptibility and increased the survival of individual E. coli cells. Genomic analysis further revealed an underrepresentation of the MazF cleavage site in genomes of RNA phages infecting E. coli, indicating selection against cleavage. These results show that, in addition to other physiological roles, RNA-degrading toxin–antitoxin systems may also help defend against RNA phages
Light-microscopy-based connectomic reconstruction of mammalian brain tissue
No full textThe information-processing capability of the brain’s cellular network depends on the physical wiring pattern between neurons and their molecular and functional characteristics. Mapping neurons and resolving their individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution1,2 with dense cellular labelling. Light microscopy is uniquely positioned to visualize specific molecules, but dense, synapse-level circuit reconstruction by light microscopy has been out of reach, owing to limitations in resolution, contrast and volumetric imaging capability. Here we describe light-microscopy-based connectomics (LICONN). We integrated specifically engineered hydrogel embedding and expansion with comprehensive deep-learning-based segmentation and analysis of connectivity, thereby directly incorporating molecular information into synapse-level reconstructions of brain tissue. LICONN will allow synapse-level phenotyping of brain tissue in biological experiments in a readily adoptable manner
A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics
No full textFor accurate perception and motor control, an animal must distinguish between sensory experiences elicited by external stimuli and those elicited by its own actions. The diversity of behaviors and their complex influences on the senses make this distinction challenging. Here, we uncover an action–cue hub that coordinates motor commands with visual processing in the brain’s first visual relay. We show that the ventral lateral geniculate nucleus (vLGN) acts as a corollary discharge center, integrating visual translational optic flow signals with motor copies from saccades, locomotion and pupil dynamics. The vLGN relays these signals to correct action-specific visual distortions and to refine perception, as shown for the superior colliculus and in a depth-estimation task. Simultaneously, brain-wide vLGN projections drive corrective actions necessary for accurate visuomotor control. Our results reveal an extended corollary discharge architecture that refines early visual transformations and coordinates actions via a distributed hub-and-spoke network to enable visual perception during action
Drivers of mesoscale convective aggregation and spatial humidity variability in the tropical western Pacific
No full textWe examine mesoscale convective organisation in the tropical western Pacific using a multivariate analysis of column humidity, precipitation and sea surface temperature (SST) observations. We demonstrate that in boreal summer and autumn, convection remains spatially random despite radiative-feedbacks acting to aggregate convection, which we attribute to the high density of convective moisture sources and the role of wind shear. Instead, in winter and spring, a weak meridional SST gradient exists and convection is usually clustered over the regions of warmer SSTs, with significant meridional humidity gradients. However, this is sporadically interrupted by episodes of convection migration to the coldest SSTs and limited spatial humidity variance. These episodes are the result of westward propagating equatorial waves, which remove meridional humidity gradients. It appears that the drivers of mesoscale convective clustering and humidity variability in the Pacific warm pool are the SST gradients, shear, and equatorial wave dynamics
An Hα view of galaxy buildup in the first 2 Gyr: Luminosity functions at z ∼ 4−6.5 from NIRCam/grism spectroscopy
No full textThe Hα nebular emission line is an optimal tracer for recent star formation in galaxies. With the advent of JWST, this line has recently become observable at z > 3 for the first time. We present a catalog of 1050 Hα emitters at 3.7 3 obtained based purely on spectroscopic data, robustly tracing galaxy star formation rates (SFRs) beyond the peak of the cosmic star formation history. We compared our results with theoretical predictions from three different simulations and found good agreement at z ∼ 4 − 6. The UV LFs of this spectroscopically confirmed sample are in good agreement with pre-JWST measurements obtained with photometrically selected objects. Finally, we derived SFR functions and integrated them to compute the evolution of the cosmic SFR densities across z ∼ 4 − 6, finding values in good agreement with recent UV estimates from Lyman-break galaxies, which imply a continuous decrease in SFR density by a factor of three over z ∼ 4 to z ∼ 6. Our work shows the power of NIRCam grism observations to efficiently provide new tests for early galaxy formation models based on emission line statistics
A framework for neural organoids, assembloids and transplantation studies
No full textAs the field of neural organoids and assembloids expands, there is an emergent need for guidance and advice on designing, conducting and reporting experiments to increase the reproducibility and utility of these models. In this Perspective, we present a framework for the experimental process that encompasses ensuring the quality and integrity of human pluripotent stem cells, characterizing and manipulating neural cells in vitro, transplantation techniques and considerations for modelling human development, evolution and disease. As with all scientific endeavours, we advocate for rigorous experimental designs tailored to explicit scientific questions as well as transparent methodologies and data sharing to provide useful knowledge for current research practices and for developing regulatory standards