Apo-Ghrelin Receptor Forms Heteromers with DRD2 in Hypothalamic Neurons and Is Essential for Anorexigenic Effects of DRD2 Agonism

SummaryWe identified subsets of neurons in the brain that coexpress the dopamine receptor subtype-2 (DRD2) and the ghrelin receptor (GHSR1a). Combination of FRET confocal microscopy and Tr-FRET established the presence of GHSR1a:DRD2 heteromers in hypothalamic neurons. To interrogate function, mice were treated with the selective DRD2 agonist cabergoline, which produced anorexia in wild-type and ghrelin−/− mice; intriguingly, ghsr−/− mice were refractory illustrating dependence on GHSR1a, but not ghrelin. Elucidation of mechanism showed that formation of GHSR1a:DRD2 heteromers allosterically modifies canonical DRD2 dopamine signaling resulting in Gβγ subunit-dependent mobilization of [Ca2+]i independent of GHSR1a basal activity. By targeting the interaction between GHSR1a and DRD2 in wild-type mice with a highly selective GHSR1a antagonist (JMV2959) cabergoline-induced anorexia was blocked. Inhibiting dopamine signaling in subsets of neurons with a GHSR1a antagonist has profound therapeutic implications by providing enhanced selectivity because neurons expressing DRD2 alone would be unaffected

One-photon Solutions to Multiqubit Multimode quantum Rabi model

General solutions to the quantum Rabi model involve subspaces with unbounded number of photons. However, for the multiqubit multimode case, we find special solutions with at most one photon for arbitrary number of qubits and photon modes. Unlike the Juddian solution, ours exists for arbitrary single qubit-photon coupling strength with constant eigenenergy. This corresponds to a horizontal line in the spectrum, while still being a qubit-photon entangled state. As a possible application, we propose an adiabatic scheme for the fast generation of arbitrary single-photon multimode W states with nonadiabatic error less than 1%. Finally, we propose a superconducting circuit design, showing the experimental feasibility of the multimode multiqubit Rabi model.Comment: 6 pages, 5 figures plus Supplemental Material

The application of a mechanistic model to analyze the factors that affect the lactation curve parameters of dairy sheep in Mexico

Pollott́s mechanistic model has been designed to describe lactation curve parameters based on the known biology of milk production and can be useful for analyzing the factors that affect this process. A total of 553 lactations (9956 weekly test-day records) of crossbred dairy sheep from four commercial farms located in Mexico, were analyzed to investigate environmental factors that influenced lactation curve parameters, using Pollott’s 5-parameter additive model. This model was fitted to each lactation using an iterative nonlinear procedure. The estimated parameters were maximum milk secretion potential (MSmax), relative rate of increase in cell differentiation (GR), maximum secretion loss (MSLmax), relative rate of decline in cell numbers (DR) and the proportion of parenchyma cells dead at parturition. A general linear model procedure was used to determine the effect of type of lambing, lambing number, flock and lambing season on total lactation milk yield (TMY), lactation length and estimated parameters of the Pollott model. Ewes had an average milk yield of 74.4 L with an average lactation length of 140 days. Flock had a significant (P < 0.05) effect on most of the analyzed traits, which can be explained by the different farmś management practices. The TMY were significantly (P = 0.005) higher for twin-lambing than single-lambing lactations. Sheep in their first lambing had lower TMY than those in their fourth lambing (P = 0.01), possibly explained by the lower values of MSmax (2.85 vs. 5.3 L) and the decrease in DR throughout life (P = 0.03). However, the relative GR was greatest (P = 0.04) during first lambing and then decreased as lambing number increased. Both lambing number and type of lambing also affected milk yield. The parameters of the Pollott model can be useful to explain, with a biological approximation, the dynamics of differentiation, secretion and death of mammary cells in dairy sheep

Elements of intensive care bereavement follow-up services: A European survey

Background: Despite technological innovations and continuous improvement in evidence-based treatments, mortality in the intensive care unit remains high. Consequently, a large group of family members may be in need, and benefit from bereavement follow-up support. Aim: To explore elements, organization, and evaluation of ICU bereavement services in European countries. Specific objectives were to investigate: 1) the model of bereavement follow-up services (elements of support), 2) the workforce model (organization of staff), 3) the evaluation model (evaluation strategies). Study design: Cross-sectional survey of conference delegates. Methods: A paper and pen questionnaire including a cover letter assuring the respondents of anonymity and confidentiality was distributed to 250 delegates during the opening ceremony of the 2017 European federation of Critical Care Nurses associations (EfCCNa) Congress in Belfast. The questionnaire was developed from a previously validated tool describing bereavement care practices in intensive care units including questions about the content and organization of bereavement follow-up services. Frequencies were calculated in yes/no questions and content analysis was applied in additional free text comments. Results: We received 85 responses from publicly employed nurses, mainly in mixed adult ICUs. Respondents were 48 (56.5%) bedside nurses and the rest represented clinical nurse specialists, researchers, managers, or academic nurses. Bereavement follow-up had existed about 1-15 years. Important follow-up elements were: viewing the deceased in the unit 77 (90.6%), providing follow-up information 67 (79.8%), sending a letter of sympathy 17 (20%), and calling the family to arrange a meeting 27 (31%). Conclusion: Bereavement follow-up is common, but variable at European intensive care units. We recommend the development, implementation, and evaluation of evidence-based, but culture-specific, bereavement follow-up guidelines for European intensive care units. Relevance to Clinical Practice: More critical care nurses are realizing the need for bereavement follow-up guidelines. This paper provides an overview of common elements that might be considered

Project AIM: Autism Intervention Meta-Analysis for Studies of Young Children

Article is forthcoming as of December 2019. Citation for published version will be added once released by the American Psychological Association.In this comprehensive systematic review and meta-analysis of group design studies of nonpharmacological early interventions designed for young children with autism spectrum disorder (ASD), we report summary effects across seven early intervention types (behavioral, developmental, naturalistic developmental behavioral intervention [NDBI], TEACCH, sensory-based, animal-assisted, and technology-based), and 15 outcome categories indexing core and related ASD symptoms. A total of 1,615 effect sizes were gathered from 130 independent participant samples. A total of 6,240 participants, who ranged in age from 0-8 years, are represented across the studies. We synthesized effects within intervention and outcome type using a robust variance estimation approach to account for the nesting of effect sizes within studies. We also tracked study quality indicators, and report an additional set of summary effect sizes that restrict included studies to those meeting pre-specified quality indicators. Finally, we conducted moderator analyses to evaluate whether summary effects across intervention types were larger for proximal as compared to distal effects, and for context-bound as compared to generalized effects. We found that when study quality indicators were not taken into account, significant positive effects were found for behavioral, developmental, and NDBI intervention types. When effect size estimation was limited to studies with randomized controlled trial (RCT) designs, evidence of positive summary effects existed only for developmental and NDBI intervention types. This was also the case when outcomes measured by parent report were excluded. Finally, when effect estimation was limited to RCT designs and to outcomes for which there was no risk of detection bias, no intervention types showed significant effects on any outcome.Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (U54HD083211; PI: Neul)Special Educatio

Classical and semi-classical energy conditions

The standard energy conditions of classical general relativity are (mostly) linear in the stress-energy tensor, and have clear physical interpretations in terms of geodesic focussing, but suffer the significant drawback that they are often violated by semi-classical quantum effects. In contrast, it is possible to develop non-standard energy conditions that are intrinsically non-linear in the stress-energy tensor, and which exhibit much better well-controlled behaviour when semi-classical quantum effects are introduced, at the cost of a less direct applicability to geodesic focussing. In this article we will first review the standard energy conditions and their various limitations. (Including the connection to the Hawking--Ellis type I, II, III, and IV classification of stress-energy tensors). We shall then turn to the averaged, nonlinear, and semi-classical energy conditions, and see how much can be done once semi-classical quantum effects are included.Comment: V1: 25 pages. Draft chapter, on which the related chapter of the book "Wormholes, Warp Drives and Energy Conditions" (to be published by Springer), will be based. V2: typos fixed. V3: small typo fixe

Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

<p>Abstract</p> <p>Background</p> <p>Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection.</p> <p>Methods</p> <p>NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays.</p> <p>Results</p> <p>We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients.</p> <p>Conclusion</p> <p>Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression.</p

Baidu, Weibo and Renren: The Global Political Economy of Social Media in China

The task of this work is to conduct a global political-economic analysis of China's major social media platforms in the context of transformations of the Chinese economy. It analyses Chinese social media's commodity and capital form. It compares the political economy of Baidu (search engine), Weibo (microblog) and Renren (social networking site) to the political economy of the US platforms Google (search engine), Twitter (microblog) and Facebook (social networking site) in order to analyse differences and commonalities. The comparative analysis focuses on aspects such as profits, the role of advertising, the boards of directors, shareholders, financial market values, terms of use and usage policies. The analysis is framed by the question to which extent China has a capitalist or socialist economy