1,904 research outputs found

    Spacetime Emergence in the Robertson-Walker Universe from a Matrix model

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    Using a novel, string theory-inspired formalism based on a Hamiltonian constraint, we obtain a conformal mechanical system for the spatially flat four-dimensional Robertson-Walker Universe. Depending on parameter choices, this system describes either a relativistic particle in the Robertson-Walker background, or metric fluctuations of the Robertson-Walker geometry. Moreover we derive a tree-level M-theory matrix model in this time-dependent background. Imposing the Hamiltonian constraint forces the spacetime geometry to be fuzzy near the big bang, while the classical Robertson-Walker geometry emerges as the Universe expands. From our approach we also derive the temperature of the Universe interpolating between the radiation and matter dominated eras.Comment: 4 pages - accepted for publication in Physical Review Letter

    Superconformal Ward Identities for Green Functions with Multiple Supercurrent Insertions

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    Superconformal Ward identities for N=1 supersymmetric quantum field theories in four dimensions are convenienty obtained in the superfield formalism by combining diffeomorphisms and Weyl transformations on curved superspace. Using this approach we study the superconformal transformation properties of Green functions with one or more insertions of the supercurrent to all orders in perturbation theory. For the case of two insertions we pay particular attention to fixing the additional counterterms present, as well as to the purely geometrical anomalies which contribute to the transformation behaviour. Moreover we show in a scheme-independent way how the quasi-local terms in the Ward identities are related to similar terms which contribute to the supercurrent two and three point functions. Furthermore we relate our superfield approach to similar studies which use the component formalism by discussing the implications of our approach for the components of the supercurrent and of the supergravity prepotentials.Comment: 35 pages, AMSLaTeX Problems with older LaTeX versions fixed, no change of conten

    Psychobiotics and fecal microbial transplantation for autism and attention-deficit/hyperactivity disorder: microbiome modulation and therapeutic mechanisms

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    Dysbiosis of the gut microbiome is thought to be the developmental origins of the host’s health and disease through the microbiota-gut-brain (MGB) axis: such as immune-mediated, metabolic, neurodegenerative, and neurodevelopmental diseases. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common neurodevelopmental disorders, and growing evidence indicates the contribution of the gut microbiome changes and imbalances to these conditions, pointing to the importance of considering the MGB axis in their treatment. This review summarizes the general knowledge of gut microbial colonization and development in early life and its role in the pathogenesis of ASD/ADHD, highlighting a promising therapeutic approach for ASD/ADHD through modulation of the gut microbiome using psychobiotics (probiotics that positively affect neurological function and can be applied for the treatment of psychiatric diseases) and fecal microbial transplantation (FMT)

    Adult Human Brain Neural Progenitor Cells (NPCs) and Fibroblast-Like Cells Have Similar Properties In Vitro but Only NPCs Differentiate into Neurons

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    The ability to culture neural progenitor cells from the adult human brain has provided an exciting opportunity to develop and test potential therapies on adult human brain cells. To achieve a reliable and reproducible adult human neural progenitor cell (AhNPC) culture system for this purpose, this study fully characterized the cellular composition of the AhNPC cultures, as well as the possible changes to this in vitro system over prolonged culture periods. We isolated cells from the neurogenic subventricular zone/hippocampus (SVZ/HP) of the adult human brain and found a heterogeneous culture population comprised of several types of post-mitotic brain cells (neurons, astrocytes, and microglia), and more importantly, two distinct mitotic cell populations; the AhNPCs, and the fibroblast-like cells (FbCs). These two populations can easily be mistaken for a single population of AhNPCs, as they both proliferate under AhNPC culture conditions, form spheres and express neural progenitor cell and early neuronal markers, all of which are characteristics of AhNPCs in vitro. However, despite these similarities under proliferating conditions, under neuronal differentiation conditions, only the AhNPCs differentiated into functional neurons and glia. Furthermore, AhNPCs showed limited proliferative capacity that resulted in their depletion from culture by 5–6 passages, while the FbCs, which appear to be from a neurovascular origin, displayed a greater proliferative capacity and dominated the long-term cultures. This gradual change in cellular composition resulted in a progressive decline in neurogenic potential without the apparent loss of self-renewal in our cultures. These results demonstrate that while AhNPCs and FbCs behave similarly under proliferative conditions, they are two different cell populations. This information is vital for the interpretation and reproducibility of AhNPC experiments and suggests an ideal time frame for conducting AhNPC-based experiments

    Patchy Forsterite Clouds in the Atmospheres of Two Highly Variable Exoplanet Analogs

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    © 2023. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/We present an atmospheric retrieval analysis of a pair of highly variable, ∼200 Myr old, early T type planetary-mass exoplanet analogs SIMP J01365662+0933473 and 2MASS J21392676+0220226 using the Brewster retrieval framework. Our analysis, which makes use of archival 1–15 μm spectra, finds almost identical atmospheres for both objects. For both targets, we find that the data is best described by a patchy, high-altitude forsterite (Mg2SiO4) cloud above a deeper, optically thick iron (Fe) cloud. Our model constrains the cloud properties well, including the cloud locations and cloud particle sizes. We find that the patchy forsterite slab cloud inferred from our retrieval may be responsible for the spectral behavior of the observed variability. Our retrieved cloud structure is consistent with the atmospheric structure previously inferred from spectroscopic variability measurements, but clarifies this picture significantly. We find consistent C/O ratios for both objects, which supports their formation within the same molecular cloud in the Carina-Near moving group. Finally, we note some differences in the constrained abundances of H2O and CO, which may be caused by data quality and/or astrophysical processes such as auroral activity and their differing rotation rates. The results presented in this work provide a promising preview of the detail with which we will characterize extrasolar atmospheres with JWST, which will yield higher-quality spectra across a wider wavelength range.Peer reviewe

    Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

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    Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease

    Mechanisms underlying the diminished sensitivity to prolactin negative feedback during lactation: Reduced STAT5 signaling and up-regulation of cytokine-inducible SH2 domain-containing protein (CIS) expression in tuberoinfundibular dopaminergic neurons

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    Hyperprolactinaemia during lactation is a consequence of the sucking stimulus and in part due to reduced prolactin (PRL) negative feedback. To date, the mechanisms involved in this diminished sensitivity to PRL feedback are unknown but may involve changes in PRL signal transduction within tuberoinfundibular dopaminergic (TIDA) neurons. Therefore, we investigated signal transducers and activators of transcription (STAT) 5 signaling in the TIDA neurons of lactating rats. Dual-label confocal immunofluorescence studies were used to determine the intracellular distribution of STAT5 within TIDA neurons in the dorsomedial arcuate nucleus. In lactating rats with pups removed for 16 h, injection of ovine PRL significantly (P < 0.05) increased the STAT5 nuclear/cytoplasmic ratio compared with vehicle-treated mothers. In contrast, ovine PRL injection did not increase the STAT5 nuclear/cytoplasmic ratio in lactating mothers with pups, demonstrating that PRL signal transduction through STAT5 is reduced in TIDA neurons in the presence of pups. To investigate possible mechanisms involved in reduced PRL signaling, we examined the expression of suppressors of cytokine signaling (SOCS) proteins. Northern analysis on whole hypothalamus showed that CIS (cytokine-inducible SH2 domain-containing protein), but not SOCS1 or SOCS3, mRNA expression was significantly (P < 0.01) up-regulated in suckled lactating rats. Semiquantitative RT-PCR on arcuate nucleus micropunches also showed up-regulation of CIS transcripts. Immunofluorescence studies demonstrated that CIS is expressed in all TIDA neurons in the dorsomedial arcuate nucleus, and the intensity of CIS staining in these neurons is significantly (P < 0.05) increased in lactating rats with sucking pups. Together, these results support the hypothesis that loss of sensitivity to PRL-negative feedback during lactation is a result of increased CIS expression in TIDA neurons
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