Lambovesen8638

The amygdala is a core component in neurobiological models of stress and stress-related pathologies, including post-traumatic stress disorder (PTSD). While numerous studies have reported increased amygdala activity following traumatic stress exposure and in PTSD, the findings regarding amygdala volume have been mixed. One reason for these mixed findings may be that the amygdala has been considered as a homogenous entity, while it in fact consists of several nuclei with unique cellular and connectivity profiles. Here, we investigated amygdala nuclei volumes of the basolateral and the centrocorticomedial complex in relation to PTSD symptom severity in 47 young survivors from the 2011 Norwegian terror attack 24-36 months post-trauma. PTSD symptoms were assessed 4-5, 14-15 and 24-36 months following the trauma. We found that increased PTSD symptom severity 24-36 months post-trauma was associated with volumetric reductions of all basolateral as well as the central and the medial nuclei. However, only the lateral nucleus was associated with longitudinal symptom development, and mediated the association between 4-5 months and 24-36 months post-trauma symptoms. The results suggest that the amygdala nuclei may be differentially associated with cross-sectional and longitudinal measures of PTSD symptom severity. As such, investigations of amygdala total volume may not provide an adequate index of the association between amygdala and stress-related mental illness.Lysine acetylation (Kac), an abundant post-translational modification (PTM) in prokaryotes, regulates various microbial metabolic pathways. However, no studies have examined protein Kac at the microbiome level, and it remains unknown whether Kac level is altered in patient microbiomes. Herein, we use a peptide immuno-affinity enrichment strategy coupled with mass spectrometry to characterize protein Kac in the microbiome, which successfully identifies 35,200 Kac peptides from microbial or human proteins in gut microbiome samples. We demonstrate that Kac is widely distributed in gut microbial metabolic pathways, including anaerobic fermentation to generate short-chain fatty acids. Applying to the analyses of microbiomes of patients with Crohn's disease identifies 52 host and 136 microbial protein Kac sites that are differentially abundant in disease versus controls. This microbiome-wide acetylomic approach aids in advancing functional microbiome research.Physical stressors play a crucial role in the progression of irritable bowel syndrome (IBS). Here we report a heterogeneous physical stress induced IBS rat model which shows depression and subsequent modulation of IBS by oral treatment of thymol. Oral administration of Thymol reduces the stress induced IBS significantly altering the stress induced gastrointestinal hypermotility, prolonged the whole gut transit time, and increased abdominal withdrawal reflex suggesting gastrointestinal hypermotility and visceral discomfort caused the onset of depression. Immunohistochemical analysis in small intestine and colon of rats shows the decreased 5-HT3AR expression level while thymol treatment normalized the 5-HT3AR expression in the stressed rats. Molecular docking studies showed that thymol competes with endogenous serotonin and an antagonist, Tropisetron and all have similar binding energies to 5-HT3AR. Molecular dynamics simulations revealed that thymol and tropisetron might have similar effects on 5-HT3AR. Our study suggest that thymol improves IBS symptoms through 5-HT3AR, could be useful for the treatment of IBS.The need for solving optimization problems is prevalent in various physical applications, including neuroscience, network design, biological systems, socio-economics, and chemical reactions. Many of these are classified as non-deterministic polynomial-time hard and thus become intractable to solve as the system scales to a large number of elements. Recent research advances in photonics have sparked interest in using a network of coupled degenerate optical parametric oscillators (DOPOs) to effectively find the ground state of the Ising Hamiltonian, which can be used to solve other combinatorial optimization problems through polynomial-time mapping. 10058-F4 manufacturer Here, using the nanophotonic silicon-nitride platform, we demonstrate a spatial-multiplexed DOPO system using continuous-wave pumping. We experimentally demonstrate the generation and coupling of two microresonator-based DOPOs on a single chip. Through a reconfigurable phase link, we achieve both in-phase and out-of-phase operation, which can be deterministically achieved at a fast regeneration speed of 400 kHz with a large phase tolerance.The transcription factor STAT3 is frequently activated in human solid and hematological malignancies and remains a challenging therapeutic target with no approved drugs to date. Here, we develop synthetic antibody mimetics, termed monobodies, to interfere with STAT3 signaling. These monobodies are highly selective for STAT3 and bind with nanomolar affinity to the N-terminal and coiled-coil domains. Interactome analysis detects no significant binding to other STATs or additional off-target proteins, confirming their exquisite specificity. Intracellular expression of monobodies fused to VHL, an E3 ubiquitin ligase substrate receptor, results in degradation of endogenous STAT3. The crystal structure of STAT3 in complex with monobody MS3-6 reveals bending of the coiled-coil domain, resulting in diminished DNA binding and nuclear translocation. MS3-6 expression strongly inhibits STAT3-dependent transcriptional activation and disrupts STAT3 interaction with the IL-22 receptor. Therefore, our study establishes innovative tools to interfere with STAT3 signaling by different molecular mechanisms.Glioblastoma contains a rare population of self-renewing brain tumor stem cells (BTSCs) which are endowed with properties to proliferate, spur the growth of new tumors, and at the same time, evade ionizing radiation (IR) and chemotherapy. However, the drivers of BTSC resistance to therapy remain unknown. The cytokine receptor for oncostatin M (OSMR) regulates BTSC proliferation and glioblastoma tumorigenesis. Here, we report our discovery of a mitochondrial OSMR that confers resistance to IR via regulation of oxidative phosphorylation, independent of its role in cell proliferation. Mechanistically, OSMR is targeted to the mitochondrial matrix via the presequence translocase-associated motor complex components, mtHSP70 and TIM44. OSMR interacts with NADH ubiquinone oxidoreductase 1/2 (NDUFS1/2) of complex I and promotes mitochondrial respiration. Deletion of OSMR impairs spare respiratory capacity, increases reactive oxygen species, and sensitizes BTSCs to IR-induced cell death. Importantly, suppression of OSMR improves glioblastoma response to IR and prolongs lifespan.