Regulation of Ethanol-Related Behavior and Ethanol Metabolism by the Corazonin Neurons and Corazonin Receptor in Drosophila melanogaster

Impaired ethanol metabolism can lead to various alcohol-related health problems. Key enzymes in ethanol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH); however, neuroendocrine pathways that regulate the activities of these enzymes are largely unexplored. Here we identified a neuroendocrine system involving Corazonin (Crz) neuropeptide and its receptor (CrzR) as important physiological regulators of ethanol metabolism in Drosophila. Crz-cell deficient (Crz-CD) flies displayed significantly delayed recovery from ethanol-induced sedation that we refer to as hangover-like phenotype. Newly generated mutant lacking Crz Receptor (CrzR01) and CrzR-knockdown flies showed even more severe hangover-like phenotype, which is causally associated with fast accumulation of acetaldehyde in the CrzR01 mutant following ethanol exposure. Higher levels of acetaldehyde are likely due to 30% reduced ALDH activity in the mutants. Moreover, increased ADH activity was found in the CrzR01 mutant, but not in the Crz-CD flies. Quantitative RT-PCR revealed transcriptional upregulation of Adh gene in the CrzR01. Transgenic inhibition of cyclic AMP-dependent protein kinase (PKA) also results in significantly increased ADH activity and AdhmRNA levels, indicating PKA-dependent transcriptional regulation of Adh by CrzR. Furthermore, inhibition of PKA or cAMP response element binding protein (CREB) in CrzR cells leads to comparable hangover-like phenotype to the CrzR01 mutant. These findings suggest that CrzR-associated signaling pathway is critical for ethanol detoxification via Crz-dependent regulation of ALDH activity and Crz-independent transcriptional regulation of ADH. Our study provides new insights into the neuroendocrine-associated ethanol-related behavior and metabolism

Feasibility Study for Elimination of the Screening Current-Induced Fields in HTS Coil

Herein, we report a feasibility study for elimination of the screening current-induced field (SCIF) in fully insulated (INS) and no-insulation (NI) GdBCO coated conductor (CC) coils exposed to an external AC magnetic field generated by background solenoid copper coils. Prior to investigating the effects of external AC magnetic fields on SCIF in the GdBCO CC coils, the magnetic flux density (B[subscript z]) was calculated using the equivalent circuit model and compared to the B[subscript z] obtained empirically to quantify the SCIF in the INS and NI coils. The value of the SCIF in the NI coil was smaller than that in the INS coil without the use of an external AC magnetic field, due to the current paths originating from the turn-to-turn and layer-to-layer contacts, suggesting that the screening current dissipated by contact resistance during charging. When the INS and NI coils were exposed to the external AC magnetic field, the B[subscript z] of the coils increased gradually, and eventually saturating to the calculated B[subscript z] values, indicating full removal of the SCIF. In addition, the SCIF of the NI coil could be removed under subjection to a lower external AC magnetic field compared to the INS coil, due to the lower SCIF occurring in the NI coil after charging.Korea (South). Ministry of Education, Science and Technology (MEST). Mid-Career Researcher Program (Grant 2012-046999)Korea (South). Ministry of Knowledge Economy (MKE). International Collaborative R&D Program (KETEP Grant 20118520020020

Extended nonlocal chiral-quark model for the heavy-light quark systems

In this talk, we report the recent progress on constructing a phenomenological effective model for the heavy-light quark systems, which consist of (u,d,s,c,b) quarks, i.e. extended nonlocal chiral-quark model (ExNLChQM). We compute the heavy-meson weak-decay constants to verify the validity of the model. From the numerical results, it turns out that (f_D, f_B, f_{D_s}, f_{B_s})=(207.54,208.13,262.56,262.39) MeV. These values are in relatively good agreement with experimental data and various theoretical estimations.Comment: 3 pages, 4 figures, Talk given at the 20th International IUPAP Conference on Few-Body Problems in Physics (FB20), 20~25 August 2012, Fukuoka, Japa

Effect of non-nutritive sugars to decrease the survivorship of spotted wing drosophila, Drosophila suzukii

In this study, we investigated the effects of non-nutritive sugars and sugar alcohols on the survivorship of spotted wing drosophila, Drosophila suzukii, and found erythritol and erythrose as potentially insecticidal to the fly. In a dose-dependent study, erythritol and erythrose significantly reduced fly longevity, with 100% mortality with 1, 0.5, 0.1 & 0.05 M doses after feeding for 7 days. When sucrose and erythritol solutions were provided separately to flies for 7 days, there was no effect on survivorship regardless of erythritol concentrations. However, with a serial combination of sucrose and erythritol solutions, fly survivorship was significantly decreased for the same period. Also, the higher dose of erythritol regardless of the sucrose dose combined showed greater mortality. In a no-choice assay, D. suzukii ingested more erythritol than sucrose or water, indicating the fly continuously fed on erythritol for 72 h. Also under no-choice conditions, erythritol and sucrose-fed flies gained more weight than water-fed flies. However, in two-choice assays, the amount of erythritol ingested was less than sucrose or water. Total sugar and glycogen levels among erythritol and erythrose-fed flies were significantly less than mannitol, sorbitol, xylitol, and sucrose-fed flies after 48 h. This indicates that these two non-nutritive sugars can’t be used a substrate for enzymes involved in sugar metabolism. Although the metabolism of erythritol and erythrose is unknown in insects, the mortality of D. suzukii flies ingesting these sugars might be caused by two potential physiological changes. The fly is starved by feeding of non-metabolizable erythritol and erythrose, or experiences abnormally high osmotic pressure in the hemolymph with erythritol molecules diffused from the midgut. Non-nutritive sugars might be used as an insecticide alone or combined with conventional or biological insecticides to enhance efficacy. If other sugar sources are present, a palatable sugar might be mixed with erythritol to elicit feeding

Construction of 3⊗33\otimes 3 entangled edge states with positive partial transposes

We construct a class of $3\otimes 3$ entangled edge states with positive partial transposes using indecomposable positive linear maps. This class contains several new types of entangled edge states with respect to the range dimensions of themselves and their partial transposes.Comment: 14 page

Prefoldin 6 mediates longevity response from heat shock factor 1 to FOXO in C-elegans

Heat shock factor 1 (HSF-1) and forkhead box O (FOXO) are key transcription factors that protect cells from various stresses. In Caenorhabditis elegans, HSF-1 and FOXO together promote a long life span when insulin/IGF-1 signaling (IIS) is reduced. However, it remains poorly understood how HSF-1 and FOXO cooperate to confer IIS-mediated longevity. Here, we show that prefoldin 6 (PFD-6), a component of the molecular chaperone prefoldin-like complex, relays longevity response from HSF-1 to FOXO under reduced IIS. We found that PFD-6 was specifically required for reduced IIS-mediated longevity by acting in the intestine and hypodermis. We showed that HSF-1 increased the levels of PFD-6 proteins, which in turn directly bound FOXO and enhanced its transcriptional activity. Our work suggests that the prefoldin-like chaperone complex mediates longevity response from HSF-1 to FOXO to increase the life span in animals with reduced IIS.11Ysciescopu

Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling

Abstract Background Human mesenchymal stem cells (hMSCs) therapy has recently been considered a promising treatment for atopic dermatitis (AD) due to their immunomodulation and tissue regeneration ability. In our previous studies, we demonstrated that hMSCs alleviate allergic inflammation in murine AD model by inhibiting the activation of mast cells and B cells. Also our phase I/IIa clinical trial showed clinical efficacy and safety of hMSCs in moderate-to-severe adult AD patients. However, hMSCs therapy against atopic dermatitis have had poor results in clinical field. Therefore, we investigated the reason behind this result. We hypothesized that drug–cell interaction could interfere with the therapeutic efficacy of stem cells, and investigated whether coadministration with pimecrolimus, one of the topical calcineurin inhibitors, could influence the therapeutic potential of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in AD. Methods hUCB-MSCs were subcutaneously injected to AD-induced mice with or without pimecrolimus topical application. To examine whether pimecrolimus influenced the immunomodulatory activity of hUCB-MSCs, hUCB-MSCs were treated with pimecrolimus. Results Pimecrolimus disturbed the therapeutic effect of hUCB-MSCs when they were co-administered in murine AD model. Moreover, the inhibitory functions of hUCB-MSCs against type 2 helper T (Th2) cell differentiation and mast cell activation were also deteriorated by pimecrolimus treatment. Interestingly, we found that pimecrolimus decreased the production of PGE2, one of the most critical immunomodulatory factors in hUCB-MSCs. And we demonstrated that pimecrolimus downregulated COX2-PGE2 axis by inhibiting nuclear translocation of NFAT3. Conclusions Coadministration of pimecrolimus with hMSCs could interfere with the therapeutic efficacy of hMSCs in atopic dermatitis, and this is the first study that figured out the interaction of hMSCs with other drugs in cell therapy of atopic dermatitis. Therefore, this study might give rise to improvement of the clinical application of hMSCs therapy and facilitate the widespread application of hMSCs in clinical field

Gemcitabine-Based Neoadjuvant Treatment in Borderline Resectable Pancreatic Ductal Adenocarcinoma: A Meta-Analysis of Individual Patient Data

Background: Non-randomized studies have investigated multi-agent gemcitabinebased neo-adjuvant therapies (GEM-NAT) in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC). Treatment sequencing and specific elements of neoadjuvant treatment are still under investigation. The present meta-analysis aims to assess the effectiveness of GEM-NAT on overall survival (OS) in BR-PDAC. Patients and Methods: A meta-analysis of individual participant data (IPD) on GEMNAT for BR-PDAC were performed. The primary outcome was OS after treatment with GEM-based chemotherapy. In the Individual Patient Data analysis data were reappraised and confirmed as BR-PDAC on provided radiological data. Results: Six studies investigating GEM-NAT were included in the IPD metanalysis. The IPD metanalysis was conducted on 271 patients who received GEM-NAT. Pooled median patient-level OS was 22.2 months (95%CI 19.1–25.2). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Median OS was 27.8 months (95%CI 23.9–31.6) in the patients who received NAT-GEM followed by resection compared to 15.4 months (95%CI 12.3–18.4) for NAT-GEM without resection and 13.0 months (95%CI 7.4–18.5) in the group of patients who received upfront surgery (p < 0.0001). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Overall survival in the R0 group was 29.3 months (95% CI 24.3–34.2) vs. 16.2 months (95% CI 7·9–24.5) in the R1 group (p = 0·001). Conclusions: The present study is the first meta-analysis combining IPD from a number of international centers with BR-PDAC in a cohort that underwent multi-agent gemcitabine neoadjuvant therapy (GEM-NAT) before surgery. GEM-NAT followed by surgical resection improve sur

Singular Cucker-Smale Dynamics

The existing state of the art for singular models of flocking is overviewed, starting from microscopic model of Cucker and Smale with singular communication weight, through its mesoscopic mean-filed limit, up to the corresponding macroscopic regime. For the microscopic Cucker-Smale (CS) model, the collision-avoidance phenomenon is discussed, also in the presence of bonding forces and the decentralized control. For the kinetic mean-field model, the existence of global-in-time measure-valued solutions, with a special emphasis on a weak atomic uniqueness of solutions is sketched. Ultimately, for the macroscopic singular model, the summary of the existence results for the Euler-type alignment system is provided, including existence of strong solutions on one-dimensional torus, and the extension of this result to higher dimensions upon restriction on the smallness of initial data. Additionally, the pressureless Navier-Stokes-type system corresponding to particular choice of alignment kernel is presented, and compared - analytically and numerically - to the porous medium equation

Agreement of the resting distal to aortic coronary pressure with the instantaneous wave-free ratio

Background: Recently, 2 randomized controlled trials showed that the instantaneous wave-free ratio (iFR), a resting coronary physiological index, is noninferior to fractional flow reserve for guiding revascularization. The resting distal to aortic coronary pressure (Pd/Pa) measured at rest is another adenosine-free index widely available in the cardiac catheterization laboratory; however, little is known about the agreement of Pd/Pa using iFR as a reference standard. Objectives: The goal of this study was to investigate the agreement of Pd/Pa with iFR. Methods: A total of 763 patients were prospectively enrolled from 12 institutions. iFR and Pd/Pa were measured under resting conditions. Using iFR ≤0.89 as a reference standard, the agreement of Pd/Pa and its best cutoff value were assessed. Results: According to the independent core laboratory analysis, iFR and Pd/Pa were analyzable in 627 and 733 patients (82.2% vs. 96.1%; p &lt; 0.001), respectively. The median iFR and Pd/Pa were 0.90 (interquartile range: 0.85 to 0.94) and 0.92 (interquartile range: 0.88 to 0.95), and the 2 indices were highly correlated (R2 = 0.93; p &lt; 0.001; iFR = 1.31 * Pd/Pa –0.31). According to the receiver-operating characteristic curve analysis, Pd/Pa showed excellent agreement (area under the curve: 0.98; 95% confidence interval: 0.97 to 0.99; p &lt; 0.001) with a best cutoff value of Pd/Pa ≤0.91. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 93.0%, 91.4%, 94.4%, 93.3%, and 92.7%, respectively. These results were similar in patients with acute coronary syndrome and stable angina. Conclusions: Pd/Pa was analyzable in a significantly higher number of patients than iFR. Pd/Pa showed excellent agreement with iFR, suggesting that it could be applied clinically in a similar fashion. (Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology? [CONTRAST]; NCT02184117)