Development of an antibody fragment that stabilizes GPCR/G-protein complexes.

Single-particle cryo-electron microscopy (cryo-EM) has recently enabled high-resolution structure determination of numerous biological macromolecular complexes. Despite this progress, the application of high-resolution cryo-EM to G protein coupled receptors (GPCRs) in complex with heterotrimeric G proteins remains challenging, owning to both the relative small size and the limited stability of these assemblies. Here we describe the development of antibody fragments that bind and stabilize GPCR-G protein complexes for the application of high-resolution cryo-EM. One antibody in particular, mAb16, stabilizes GPCR/G-protein complexes by recognizing an interface between Gα and Gβγ subunits in the heterotrimer, and confers resistance to GTPγS-triggered dissociation. The unique recognition mode of this antibody makes it possible to transfer its binding and stabilizing effect to other G-protein subtypes through minimal protein engineering. This antibody fragment is thus a broadly applicable tool for structural studies of GPCR/G-protein complexes

Rosai-dorfman disease: report of a rare case of peripheral lymphadenopathy.

Rosai-Dorfman disease (RDD), also called Sinus histiocytosis is an uncommon proliferative disorder of unknown aetiology. Though, the lymph node is the revelation mode of several diseases particularly in the tropics, RDD typically presents with painless bilateral lymphadenopathy in the neck associated with fever and leukocytosis, sometimesmimics lympho-proliferative disorders. Recently research has unveiled gene mutation in the tumour with potential of malignant transformation. Case report:We report case of 4 year old boy who had massive cervical lymphadenopathy with extranodal manifestation of fever. Sepsis screening was negative, while imagingshowed hilar,mediastenal andmesenteric lymph nodes enlargement in addition to massive hepatomegaly. The histology is suggestive of the diagnosis of RDD. The patient was treated with corticosteroids, with remarkable remission. Conclusion: We report the clinicopathological characteristics of RDD in order to increase our awareness of its diagnosis and treatment and to re-emphasize that the disease is rare in our environment

How do enamelysin and kallikrein 4 process the 32-kDa enamelin?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74876/1/j.1600-0722.2006.00281.x.pd

Quantum fluctuations in high field magnetization of 2D square lattice J1-J2 antiferromagnets

The J1-J2 square lattice Heisenberg model with spin S=1/2 has three phases with long-range magnetic order and two unconventionally ordered phases depending on the ratio of exchange constants. It describes a number of recently found layered vanadium oxide compounds. A simple means of investigating the ground state is the study of the magnetization curve and high-field susceptibility. We discuss these quantities by using the spin-wave theory and the exact diagonalization in the whole J1-J2 plane. We compare both results and find good overall agreement in the sectors of the phase diagram with magnetic order. Close to the disordered regions the magnetization curve shows strong deviations from the classical linear behaviour caused by large quantum fluctuations and spin-wave approximation breaks down. On the FM side (J1<0) where one approaches the quantum gapless spin nematic ground state this region is surprisingly large. We find that inclusion of second order spin-wave corrections does not lead to fundamental improvement. Quantum corrections to the tilting angle of the ordered moments are also calculated. They may have both signs, contrary to the always negative first order quantum corrections to the magnetization. Finally we investigate the effect of the interlayer coupling and find that the quasi-2D picture remains valid up to |J_\perp/J1| ~ 0.3.Comment: 13 pages, 6figure

Bone Marrow Stem Cell Treatment for Ischemic Heart Disease in Patients with No Option of Revascularization: A Systematic Review and Meta-Analysis

PMCID: PMC3686792This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Evidence Base of Clinical Studies on Qi Gong: A Bibliometric Analysis

© 2020 The Authors Objective: This bibliometric study aimed to systematically and comprehensively summarize the volume, breadth and evidence for clinical research on Qigong. And this bibliometric analysis also can provide the evidence of this field. Design: Bibliometric analysis. Methods: All types of primary and secondary studies on humans were included: systematic reviews, randomized clinical trials, non-randomized controlled clinical studies, case series and case reports. Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Chinese Academic Conference Papers Database and Chinese Dissertation Database, PubMed and the Cochrane Library were searched from the date of inception to December 10, 2018. Bibliometric information, such as publication information, disease/condition, Qigong intervention and research results were extracted and analyzed. Results: A total of 886 clinical studies were identified: including 47 systematic reviews, 705 randomized clinical trials, 116 non-randomized controlled clinical studies, 12 case series and 6 case reports. The studies were conducted in 14 countries. The top 15 diseases/conditions studied were: diabetes, chronic obstructive pulmonary disease, hypertension, stroke, cervical spondylosis, lumbar disc herniation, insomnia, knee osteoarthritis, low back pain, and osteoporosis, Coronary heart disease, breast cancer, periarthritis of shoulder, depression, metabolic syndrome. Of the various Qigong exercises reported in these 886 clinical studies, Ba Duan Jin was the most frequently researched in 492 (55.5%) studies, followed by Health Qigong 107 (12.1%), Dao Yin Shu 85 (9.6%), Wu Qin Xi 67 (7.6%) and Yi Jin Jing 66 (7.4%). The most frequently used comparisons in randomized trials were maintaining normal way of life unchanged 149 (18.1%), the remaining controls included conventional treatment, mainly western medicine, Chinese herbal medicine, acupuncture, health education, psychological therapy, Yoga, Tai Chi and other non-drug therapy. The most frequently reported outcomes were physical function, quality of life, symptoms, pain and mental health indicators. Beneficial results from practicing Qigong were reported in 97% of studies. Conclusions: Qigong research publications have been increasing gradually. Reports on study types, participants, Qigong Intervention, and outcomes are diverse and inconsistent. There is an urgent need to develop a set of reporting standards for various interventions of Qigong. Further trials of high methodological quality with sufficient sample size and real world studies are needed to verify the effects of Qigong in health and disease management

The conceptualisation and measurement of DSM-5 Internet Gaming Disorder: the development of the IGD-20 Test

Background: Over the last decade, there has been growing concern about ‘gaming addiction’ and its widely documented detrimental impacts on a minority of individuals that play excessively. The latest (fifth) edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) included nine criteria for the potential diagnosis of Internet Gaming Disorder (IGD) and noted that it was a condition that warranted further empirical study. Aim: The main aim of this study was to develop a valid and reliable standardised psychometrically robust tool in addition to providing empirically supported cut-off points. Methods: A sample of 1003 gamers (85.2% males; mean age 26 years) from 57 different countries were recruited via online gaming forums. Validity was assessed by confirmatory factor analysis (CFA), criterion-related validity, and concurrent validity. Latent profile analysis was also carried to distinguish disordered gamers from non-disordered gamers. Sensitivity and specificity analyses were performed to determine an empirical cut-off for the test. Results: The CFA confirmed the viability of IGD-20 Test with a six-factor structure (salience, mood modification, tolerance, withdrawal, conflict and relapse) for the assessment of IGD according to the nine criteria from DSM-5. The IGD-20 Test proved to be valid and reliable. According to the latent profile analysis, 5.3% of the total participants were classed as disordered gamers. Additionally, an optimal empirical cut-off of 71 points (out of 100) seemed to be adequate according to the sensitivity and specificity analyses carried

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit