Highlights • Vasopressin 1a receptor binding is diffuse and widespread in the titi monkey brain. • Oxytocin receptor binding is much more limited, with the densest binding in the hippocampus. • There ...is considerable interspecies variation in neuropeptide receptor expression in primates. • ALS-II-69 is a selective antagonist for the titi monkey oxytocin receptor. • SR49059 is a selective antagonist for the titi monkey vasopressin 1a receptor.
For modern security, devices, individuals, and communications require unprecedentedly unique identifiers and cryptographic keys. One emerging method for guaranteeing digital security is to take ...advantage of a physical unclonable function. Surprisingly, native silk, which has been commonly utilized in everyday life as textiles, can be applied as a unique tag material, thereby removing the necessary apparatus for optical physical unclonable functions, such as an objective lens or a coherent light source. Randomly distributed fibers in silk generate spatially chaotic diffractions, forming self-focused spots on the millimeter scale. The silk-based physical unclonable function has a self-focusing, low-cost, and eco-friendly feature without relying on pre-/post-process for security tag creation. Using these properties, we implement a lens-free, optical, and portable physical unclonable function with silk identification cards and study its characteristics and reliability in a systemic manner. We further demonstrate the feasibility of the physical unclonable functions in two modes: authentication and data encryption.
Abstract Despite its debilitating symptoms, the pathophysiology of bipolar disorder (BD) remains unclear. One consistently compelling finding, however, has been the presence of oxidative stress. In ...the present investigation, we conducted a meta-analysis of studies that measured oxidative stress markers in BD patients compared to healthy controls. Search terms and selection criteria were determined a priori to identify and include all studies that measured a marker of oxidative stress in BD compared to healthy controls. Eight markers were included: superoxide dismutase, catalase, protein carbonyl, glutathione peroxidase, 3-nitrotyrosine, lipid peroxidation, nitric oxide, and DNA/RNA damage. A meta-analysis of standardized means was conducted using a random-effects model with generic inverse weighting. Between-study heterogeneity, publication bias, and sensitivity analyses were also examined for each marker. Twenty-seven papers were included in the meta-analysis, which comprised a total of 971 unique patients with BD and 886 healthy controls. Lipid peroxidation, DNA/RNA damage, and nitric oxide were significantly increased in BD patients compared to healthy controls. Additionally, the effect size for lipid peroxidation was very high. Publication bias was not detected for any of the markers. The main limitations in this meta-analysis are the high degree of heterogeneity between studies and the small number of studies used in the analysis of some markers. Additionally, the sensitivity analysis indicated that some results are not very robust. The results from this meta-analysis support the role of oxidative stress in bipolar disorder, especially to DNA, RNA, and lipids.
Successful embryo implantation requires a receptive endometrium. Poor uterine receptivity can account for implantation failure in women who experience recurrent pregnancy loss or multiple rounds of ...unsuccessful in vitro fertilization cycles. Here, we demonstrate that the transcription factor Forkhead Box O1 (FOXO1) is a critical regulator of endometrial receptivity in vivo. Uterine ablation of Foxo1 using the progesterone receptor Cre (PgrCre) mouse model resulted in infertility due to altered epithelial cell polarity and apoptosis, preventing the embryo from penetrating the luminal epithelium. Analysis of the uterine transcriptome after Foxo1 ablation identified alterations in gene expression for transcripts involved in the activation of cell invasion, molecular transport, apoptosis, β-catenin (CTNNB1) signaling pathway, and an increase in PGR signaling. The increase of PGR signaling was due to PGR expression being retained in the uterine epithelium during the window of receptivity. Constitutive expression of epithelial PGR during this receptive period inhibited expression of FOXO1 in the nucleus of the uterine epithelium. The reciprocal expression of PGR and FOXO1 was conserved in human endometrial samples during the proliferative and secretory phase. This demonstrates that expression of FOXO1 and the loss of PGR during the window of receptivity are interrelated and critical for embryo implantation.
Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor that triggers intracellular protein tyrosine phosphorylation. Recent genome-wide association studies have ...shown that a rare R47H mutation of TREM2 correlates with a substantial increase in the risk of developing Alzheimer’s disease (AD). To address the basis for this genetic association, we studied TREM2 deficiency in the 5XFAD mouse model of AD. We found that TREM2 deficiency and haploinsufficiency augment β-amyloid (Aβ) accumulation due to a dysfunctional response of microglia, which fail to cluster around Aβ plaques and become apoptotic. We further demonstrate that TREM2 senses a broad array of anionic and zwitterionic lipids known to associate with fibrillar Aβ in lipid membranes and to be exposed on the surface of damaged neurons. Remarkably, the R47H mutation impairs TREM2 detection of lipid ligands. Thus, TREM2 detects damage-associated lipid patterns associated with neurodegeneration, sustaining the microglial response to Aβ accumulation.
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•TREM2 deficiency augments Aβ accumulation and neuronal loss in a mouse model of AD•TREM2 sustains the microglial response to Aβ plaques by promoting microglial survival•TREM2 senses anionic lipids that have been found to interact with fibrillar Aβ•TREM2 R47H mutation linked to Alzheimer’s disease impairs lipid recognition
TREM2 acts in microglia as a sensor for a wide array of lipids that are associated with β-amyloid accumulation and neuronal loss. The TREM2 mutation that has recently been identified as a risk factor for Alzheimer’s disease attenuates microglial detection of damage-associated lipids, providing a mechanistic basis for the genetic association.
Liver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as ...their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability, and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI.
Titanium-based porous transport layers (PTL) used in polymer electrolyte membrane (PEM) water electrolyzers suffer from surface passivation (titanium oxidation), which increases the interface ...resistance between the PTL and electrode. For long-term operation, PTLs are typically coated with considerable amounts of platinum or gold to ensure reasonable performance profiles over time. Moreover, it is well known that the oxide forms of platinum and gold are not stable under electrolysis conditions. In this study, an easy and scalable method is introduced to protect the titanium PTL from passivation by sputtering very thin layers of iridium onto commercially-available titanium PTLs. The iridium layer reduces the overall ohmic resistance of the PTL/catalyst layer interface and improves the cell's performance to that achieved with carbon-based PTLs. The coating process homogeneously deposited iridium throughout the inner structure of the PTL. The findings of this study may lead to the use of iridium as a protective layer for titanium PTLs, potentially enable operation at increased cell voltages and lead to increased electrolyzer durability.
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•Easy and scalable method is introduced to protect the titanium PTL from passivation.•Very thin layers of iridium onto commercially off-the-shelf available titanium PTLs were used.•Reduced the contact resistance by 70 mΩ·cm2 and significantly improved the cell performance
Spectral response (or sensitivity) functions of a three-color image sensor (or trichromatic camera) allow a mapping from spectral stimuli to RGB color values. Like biological photosensors, digital ...RGB spectral responses are device dependent and significantly vary from model to model. Thus, the information on the RGB spectral response functions of a specific device is vital in a variety of computer vision as well as mobile health (mHealth) applications. Theoretically, spectral response functions can directly be measured with sophisticated calibration equipment in a specialized laboratory setting, which is not easily accessible for most application developers. As a result, several mathematical methods have been proposed relying on standard color references. Typical optimization frameworks with constraints are often complicated, requiring a large number of colors. We report a compressive sensing framework in the frequency domain for accurately predicting RGB spectral response functions only with several primary colors. Using a scientific camera, we first validate the estimation method with direct spectral sensitivity measurements and ensure that the root mean square errors between the ground truth and recovered RGB spectral response functions are negligible. We further recover the RGB spectral response functions of smartphones and validate with an expanded color checker reference. We expect that this simple yet reliable estimation method of RGB spectral sensitivity can easily be applied for color calibration and standardization in machine vision, hyperspectral filters, and mHealth applications that capitalize on the built-in cameras of smartphones.
Oxytocin-dependent consolation behavior in rodents Burkett, J. P.; Andari, E.; Johnson, Z. V. ...
Science (American Association for the Advancement of Science),
01/2016, Letnik:
351, Številka:
6271
Journal Article
Recenzirano
Odprti dostop
Consolation behavior toward distressed others is common in humans and great apes, yet our ability to explore the biological mechanisms underlying this behavior is limited by its apparent absence in ...laboratory animals. Here, we provide empirical evidence that a rodent species, the highly social and monogamous prairie vole (Microtus ochrogaster), greatly increases partner-directed grooming toward familiar conspecifics (but not strangers) that have experienced an unobserved stressor, providing social buffering. Prairie voles also match the fear response, anxiety-related behaviors, and corticosterone increase of the stressed cagemate, suggesting an empathy mechanism. Exposure to the stressed cagemate increases activity in the anterior cingulate cortex, and oxytocin receptor antagonist infused into this region abolishes the partner-directed response, showing conserved neural mechanisms between prairie vole and human.
The inability of neutrophils to eradicate Pseudomonas aeruginosa within the cystic fibrosis (CF) airway eventually results in chronic infection by the bacteria in nearly 80 percent of patients. ...Phagocytic killing of P. aeruginosa by CF neutrophils is impaired due to decreased cystic fibrosis transmembrane conductance regulator (CFTR) function and virulence factors acquired by the bacteria. Recently, neutrophil extracellular traps (NETs), extracellular structures composed of neutrophil chromatin complexed with granule contents, were identified as an alternative mechanism of pathogen killing. The hypothesis that NET-mediated killing of P. aeruginosa is impaired in the context of the CF airway was tested. P. aeruginosa induced NET formation by neutrophils from healthy donors in a bacterial density dependent fashion. When maintained in suspension through continuous rotation, P. aeruginosa became physically associated with NETs. Under these conditions, NETs were the predominant mechanism of killing, across a wide range of bacterial densities. Peripheral blood neutrophils isolated from CF patients demonstrated no impairment in NET formation or function against P. aeruginosa. However, isogenic clinical isolates of P. aeruginosa obtained from CF patients early and later in the course of infection demonstrated an acquired capacity to withstand NET-mediated killing in 8 of 9 isolates tested. This resistance correlated with development of the mucoid phenotype, but was not a direct result of the excess alginate production that is characteristic of mucoidy. Together, these results demonstrate that neutrophils can kill P. aeruginosa via NETs, and in vitro this response is most effective under non-stationary conditions with a low ratio of bacteria to neutrophils. NET-mediated killing is independent of CFTR function or bacterial opsonization. Failure of this response in the context of the CF airway may occur, in part, due to an acquired resistance against NET-mediated killing by CF strains of P. aeruginosa.
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