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Galaxy-galaxy strong lensing in galaxy clusters is a unique tool for studying the subhalo mass distribution, as well as for testing predictions from cosmological simulations. We describe a novel method that simulates realistic lensed features embedded inside the complexity of observed data by exploiting high-precision cluster lens models. Such methodology is used to build a large dataset with which Convolutional Neural Networks have been trained to identify strong lensing events in galaxy clusters. In particular, we inject lensed sources around cluster members using the images acquired by the Hubble Space Telescope. The resulting simulated mock data preserve the complexity of observation by taking into account all the physical components that could affect the morphology and the luminosity of the lensing events. The trained networks achieve a purity-completeness level of ∼ 91% in detecting such events. The methodology presented can be extended to other data-intensive surveys carried out with the next-generation facilities. [ABSTRACT FROM AUTHOR]

In any imaging survey, measuring accurately the astronomical background light is crucial to obtain good photometry. This paper introduces BKGnet , a deep neural network to predict the background and its associated error. BKGnet has been developed for data from the Physics of the Accelerating Universe Survey (PAUS), an imaging survey using a 40 narrow-band filter camera (PAUCam). The images obtained with PAUCam are affected by scattered light: an optical effect consisting of light multiply reflected that deposits energy in specific detector regions affecting the science measurements. Fortunately, scattered light is not a random effect, but it can be predicted and corrected for. We have found that BKGnet background predictions are very robust to distorting effects, while still being statistically accurate. On average, the use of BKGnet improves the photometric flux measurements by |$7{{\ \rm per\ cent}}$| and up to |$20{{\ \rm per\ cent}}$| at the bright end. BKGnet also removes a systematic trend in the background error estimation with magnitude in the i band that is present with the current PAU data management method. With BKGnet , we reduce the photometric redshift outlier rate by |$35{{\ \rm per\ cent}}$| for the best |$20{{\ \rm per\ cent}}$| galaxies selected with a photometric quality parameter. [ABSTRACT FROM AUTHOR]

Neurons in the locus coeruleus (LC) have been traditionally viewed as a homogenous population. Recent studies begin to reveal their heterogeneity at multiple levels, ranging from molecular compositions to projection targets. To further uncover variations of neuronal properties in the LC, we took a genetic-based tagging approach to identify these neurons. Our data revealed diverse spike waveforms among neurons in the LC region, including a considerable fraction of narrow-spiking units. While all wide-spiking units possessed the regular waveform polarity (negative-positive deflection), the narrow units can be further divided based on opposing waveform polarities. Under anesthesia, wide units emitted action potential at a higher rate than the narrow units. Under wakefulness, only one subtype of narrow units exhibited fast-spiking phenotype. These neurons also had long latencies to optogenetic stimulation. In-situ hybridization further supported the existence of a small population of putative GABAergic neurons in the LC core. Together, our data reveal characteristic differences among neurons in the LC region, and suggest that a fraction of electrophysiologically-identified narrow-spiking neurons can be fast-spiking interneurons, and their fast-spiking feature is masked by anesthesia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Delirium is a highly prevalent neuropsychiatric syndrome characterised by acute and fluctuating impairments in attention and cognition. Mechanisms driving delirium are poorly understood but it has been suggested that blood cytokines and chemokines cross the blood brain barrier during delirium, directly impairing brain function. It is not known whether these molecules reach higher brain levels when the blood cerebrospinal fluid barrier (BCSFB) is impaired. Here, in human hip-fracture patients, we tested the influence of BCSFB integrity on CSF levels of chemokines and assessed their association with delirium. CSF levels of IP-10, eotaxin, eotaxin 3 and TARC showed weak to moderate correlations with BCSFB permeability, as measured by the Q albumin ratio, while MCP1, IL-8, MIP1α and MIP1β showed no significant correlation. Chemokines were not associated with delirium in univariate analysis or when stratified on dementia status, but exploratory analyses showed that elevated Eotaxin (CCL11) and MIP1α (CCL3) were associated with prevalent delirium. Modelling acute systemic inflammation, we used bacterial LPS (250 μg/kg) or sterile laparotomy surgery in mice to demonstrate de novo synthesis of chemokines at the choroid plexus (CP) and microvasculature. Gene expression data showed CP-enriched expression of Il1b, Tnfa, Cxcl1 and Ccl3 in both models and immunohistochemistry showed cytokine and chemokine synthesis in CP stromal (IL-1β, CCL2/MCP1) or epithelial cells (CXCL10/IP-10) cells and at the microvasculature. Larger studies are required to confirm these human findings on chemokine associations with BCSFB permeability and prevalent delirium. Preclinical studies are warranted to determine whether chemokines might play a role in the pathophysiology of delirium., Competing Interests: The authors declare that they have are no financial or other conflicts of interest relevant to the data presented in this manuscript., (© 2024 The Authors.)

Age is a significant but heterogeneous risk factor for acute neuropsychiatric disturbances such as delirium. Neuroinflammation increases with aging but the determinants of underlying risk for acute dysfunction upon systemic inflammation are not clear. We hypothesised that, with advancing age, mice would become progressively more vulnerable to acute cognitive dysfunction and that neuroinflammation and neuronal integrity might predict heterogeneity in such vulnerability. Here we show region-dependent differential expression of microglial transcripts, but a ubiquitously observed primed signature: chronic Clec7a expression and exaggerated Il1b responses to systemic bacterial LPS. Cognitive frailty (vulnerability to acute disruption under acute stressors LPS and double stranded RNA; poly I:C) was increased in aged animals but showed heterogeneity and was significantly correlated with reduced myelin density, synaptic loss and severity of white matter microgliosis. The data indicate that white matter disruption and neuroinflammation may be key substrates of the progressive but heterogeneous risk for delirium in aged individuals., (© 2024. The Author(s).)

Double stranded RNA is generated during viral replication. The synthetic analogue poly I:C is frequently used to mimic anti-viral innate immune responses in models of psychiatric and neurodegenerative disorders including schizophrenia, autism, Parkinson's disease and Alzheimer's disease. Many studies perform limited analysis of innate immunity despite these responses potentially differing as a function of dsRNA molecular weight and age. Therefore fundamental questions relevant to impacts of systemic viral infection on brain function and integrity remain. Here, we studied innate immune-inducing properties of poly I:C preparations of different lengths and responses in adult and aged mice. High molecular weight (HMW) poly I:C (1-6 kb, 12 mg/kg) produced more robust sickness behavior and more robust IL-6, IFN-I and TNF-α responses than poly I:C of < 500 bases (low MW) preparations. This was partly overcome with higher doses of LMW (up to 80 mg/kg), but neither circulating IFNβ nor brain transcription of Irf7 were significantly induced by LMW poly I:C, despite brain Ifnb transcription, suggesting that brain IFN-dependent gene expression is predominantly triggered by circulating IFNβ binding of IFNAR1. In aged animals, poly I:C induced exaggerated IL-6, IL-1β and IFN-I in the plasma and similar exaggerated brain cytokine responses. This was associated with acute working memory deficits selectively in aged mice. Thus, we demonstrate dsRNA length-, IFNAR1- and age-dependent effects on anti-viral inflammation and cognitive function. The data have implications for CNS symptoms of acute systemic viral infection such as those with SARS-CoV-2 and for models of maternal immune activation., (Copyright © 2021. Published by Elsevier Inc.)

Double stranded RNA is generated during viral replication. The synthetic analog poly I:C is frequently used to mimic anti-viral innate immune responses in models of psychiatric and neurodegenerative disease including autism, schizophrenia, Parkinsons disease and Alzheimers disease. Many studies perform limited analysis of innate immunity despite these responses potentially differing as a function of dsRNA molecular weight and age. Therefore fundamental questions relevant to impacts of systemic viral infection on brain function and integrity remain. Here, we studied innate immune-inducing properties of poly I:C preparations of different lengths and responses in adult and aged mice. High molecular weight (HMW) poly I:C (1 to 6 kb, 12 mg/kg) produced more robust sickness behavior and more robust IL-6, IFN-I and TNF alpha responses than poly I:C of less than 500 bases (low MW) preparations. This was partly overcome with higher doses of LMW (up to 80 mg/kg), but neither circulating IFN beta nor brain transcription of Irf7 were significantly induced by LMW poly I:C, despite brain Ifnb transcription, suggesting that brain IFN-dependent gene expression is predominantly triggered by circulating IFN beta binding of IFNAR1. In aged animals, poly I:C induced exaggerated IL-6, IL-1beta and IFN-I in the plasma and similar exaggerated brain cytokine responses. This was associated with acute working memory deficits selectively in aged mice. Thus, we demonstrate dsRNA length, IFNAR1 and age-dependent effects on antiviral inflammation and cognitive function. The data have implications for CNS symptoms of acute systemic viral infection such as those with SARS-CoV-2 and for models of maternal immune activation.

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consolidation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irreversible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI-dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

Type I interferons (IFN-I) are the principal antiviral molecules of the innate immune system and can be made by most cell types, including central nervous system cells. IFN-I has been implicated in neuroinflammation during neurodegeneration, but its mechanism of induction and its consequences remain unclear. In the current study, we assessed expression of IFN-I in murine prion disease (ME7) and examined the contribution of the IFN-I receptor IFNAR1 to disease progression. The data indicate a robust IFNβ response, specifically in microglia, with evidence of IFN-dependent genes in both microglia and astrocytes. This IFN-I response was absent in stimulator of interferon genes (STING -/- ) mice. Microglia showed increased numbers and activated morphology independent of genotype, but transcriptional signatures indicated an IFNAR1-dependent neuroinflammatory phenotype. Isolation of microglia and astrocytes demonstrated disease-associated microglial induction of Tnfα, Tgfb1, and of phagolysosomal system transcripts including those for cathepsins, Cd68, C1qa, C3, and Trem2, which were diminished in IFNAR1 and STING deficient mice. Microglial increases in activated cathepsin D, and CD68 were significantly reduced in IFNAR1 -/- mice, particularly in white matter, and increases in COX-1 expression, and prostaglandin synthesis were significantly mitigated. Disease progressed more slowly in IFNAR1 -/- mice, with diminished synaptic and neuronal loss and delayed onset of neurological signs and death but without effect on proteinase K-resistant PrP levels. Therefore, STING-dependent IFN-I influences microglial phenotype and influences neurodegenerative progression despite occurring secondary to initial degenerative changes. These data expand our mechanistic understanding of IFN-I induction and its impact on microglial function during chronic neurodegeneration., (© 2019 The Authors. Glia published by Wiley Periodicals, Inc.)

The role of the choroid plexus (CP) in iron (Fe) homeostasis has been suggested as the main mechanism of Fe uptake and storage in the mammalian central nervous system. Thus, the CP of the lateral and fourth ventricles was studied in guinea pigs with light and electron microscopy using methods including Perls' Prussian blue and Gomori acid phosphatase staining, immunoreactivity for ferritin and transferrin, as well as energy dispersive spectrometry microanalysis. The present study reveals the presence of endogenous Fe in CP epithelial cells. Under light microscopy, Prussian blue staining revealed dark blue precipitates (i.e., Fe 3+ ) with a preferentially perinuclear localization. The Fe was also positive for such granules with similar cellular localization. Ultrastructural analysis demonstrated the presence of dense bodies and siderosomes with molecular ferritin. The spectra obtained by the microanalysis demonstrated emissions for Fe, both in dense bodies and siderosomes. This study suggests that guinea pig CP epithelial cells accumulate Fe in the form of ferritin, possibly in cytoplasmic organelles such as lysosomes., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Diabetes mellitus is a disease associated with several changes in the central nervous system, including oxidative stress and abnormal glutamatergic neurotransmission, and the astrocytes play an essential role in these alterations. In vitro studies of astroglial function have been performed using cultures of primary astrocytes or C6 glioma cells. Herein, we investigated glutamate uptake, glutamine synthetase and S100B secretion in C6 glioma cells cultured in a high-glucose environment, as well as some parameters of oxidative stress and damage. C6 glioma cells, cultured in 12 mM glucose medium, exhibited signals of oxidative and nitrosative stress similar to those found in diabetes mellitus and other models of diabetic disease (decrease in glutathione, elevated NO, DNA damage). Interestingly, we found an increase in glutamate uptake and S100B secretion, and a decrease in glutamine synthetase, which might be linked to the altered glutamatergic communication in diabetes mellitus. Moreover, glutamate uptake in C6 glioma cells, like primary astrocytes, was stimulated by extracellular S100B. Aminoguanidine partially prevented the glial alterations induced by the 12 mM glucose medium. Together, these data emphasize the relevance of astroglia in diabetes mellitus, as well as the importance of glial parameters in the evaluation of diabetic disease progression and treatment.