Crystal structure of deglycosylated human IgG4-Fc

The Fc region of IgG antibodies, important for effector functions such as antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis and complement activation, contains an oligosaccharide moiety covalently attached to each C_H2 domain. The oligosaccharide not only orients the C_H2 domains but plays an important role in influencing IgG effector function, and engineering the IgG-Fc oligosaccharide moiety is an important aspect in the design of therapeutic monoclonal IgG antibodies. Recently we reported the crystal structure of glycosylated IgG4-Fc, revealing structural features that could explain the anti-inflammatory biological properties of IgG4 compared with IgG1. We now report the crystal structure of enzymatically deglycosylated IgG4-Fc, derived from human serum, at 2.7 Å resolution. Intermolecular C_H2-C_H2 domain interactions partially bury the C_H2 domain surface that would otherwise be exposed by the absence of oligosaccharide, and two Fc molecules are interlocked in a symmetric, open conformation. The conformation of the C_H2 domain DE loop, to which oligosaccharide is attached, is altered in the absence of carbohydrate. Furthermore, the C_H2 domain FG loop, important for Fcγ receptor and C1q binding, adopts two different conformations. One loop conformation is unique to IgG4 and would disrupt binding, consistent with IgG4's anti-inflammatory properties. The second is similar to the conserved conformation found in IgG1, suggesting that in contrast to IgG1, the IgG4 C_H2 FG loop is dynamic. Finally, crystal packing reveals a hexameric arrangement of IgG4-Fc molecules, providing further clues about the interaction between C1q and IgG.     

μ、κ、δ阿片受体及酪氨酸羟化酶在MN9D细胞中的表达

目的:检测多巴胺能性MN9D细胞中是否存在μ、κ、δ 3种阿片类受体及多巴胺能神经元特异性标记物酪氨酸羟化酶(TH)的表达,为建立吗啡依赖MN9D细胞模型奠定基础.方法:培养MN9D细胞后,采用免疫荧光标记观察μ、κ、δ3种受体蛋白表达状态;RT-PCR检测μ、κ、δ3种阿片类受体的mRNA表达;TH免疫荧光标记,观察多巴胺能神经元的表达数量.结果:免疫荧光及PCR结果均显示MN9D细胞中存在μ、κ、δ 3种受体,并且TH阳性细胞的数目明显多于多巴胺能SH-SY5Y细胞系.结论:MN9D细胞中同时存在μ、κ、δ3种阿片受体,可作为吗啡依赖细胞模型使用.     

Cytomegalovirus-induced pathology in human temporal bones with congenital and acquired infection

ObjectivePublications on histopathology of human temporal bones with cytomegalovirus (CMV) infection are limited. We aim to determine histopathology of the inner ears and the middle ears in human temporal bones with congenital and acquired CMV infections.MethodsTemporal bones from 2 infants with congenital and 2 adults with acquired CMV infection were evaluated by light microscopy.ResultsTwo infants with congenital CMV infection showed striking pathological changes in the inner ear. There was a hypervascularization of the stria vascularis in the cochlea of the first infant, but no obvious loss of outer and inner hair cells was seen in the organ of Corti. However, cytomegalic cells and a loss of outer hair cells were found in the cochlea of the second infant. The vestibular organs of both infants showed cytomegalic cells, mostly located on dark cells. There was a loss of type I and type II hair cells in the macula of the saccule and utricle. Loss of hair cells and degeneration of nerve fibers was also seen in the semicircular canals. Both infants with congenital infection showed abundant inflammatory cells and fibrous structures in the middle ear cavity. No evidence of cytomegalic cells and hair cell loss was found in the cochlea or vestibular labyrinth in acquired CMV infection.ConclusionsIn two infants with congenital CMV infection, the cochlea, vestibule, and middle ear were highly affected. Temporal bones of adult donors with acquired viral infection showed histological findings similar to donors of the same age without ear disease.     

山茱萸炮制增效活性部位对老年小鼠骨髓细胞MN影响的研究

目的:探讨山茱萸炮制增效活性部位对老年小鼠骨髓细胞微核(MN)的影响。方法:取青年组、老年组、用药组(山茱萸制品几种溶剂萃取部位)小鼠的骨髓细胞,检测MN,统计微核率。结果:老年组与青年组相比,微核率差异显著,而两个用药组分别用石油醚萃取部位、水煎液灌胃,小鼠骨髓细胞微核率与老年组相比差异显著,表现出一定的药效。结论:山茱萸制品水煎液及山茱萸制品石油醚萃取部位对老年小鼠骨髓细胞DNA有一定的保护作用。     

A Survey of Deep-Learning Applications in Ultrasound: Artificial Intelligence–Powered Ultrasound for Improving Clinical Workflow

Ultrasound is the most commonly used imaging modality in clinical practice because it is a nonionizing, low-cost, and portable point-of-care imaging tool that provides real-time images. Artificial intelligence (AI)–powered ultrasound is becoming more mature and getting closer to routine clinical applications in recent times because of an increased need for efficient and objective acquisition and evaluation of ultrasound images. Because ultrasound images involve operator-, patient-, and scanner-dependent variations, the adaptation of classical machine learning methods to clinical applications becomes challenging. With their self-learning ability, deep-learning (DL) methods are able to harness exponentially growing graphics processing unit computing power to identify abstract and complex imaging features. This has given rise to tremendous opportunities such as providing robust and generalizable AI models for improving image acquisition, real-time assessment of image quality, objective diagnosis and detection of diseases, and optimizing ultrasound clinical workflow. In this report, the authors review current DL approaches and research directions in rapidly advancing ultrasound technology and present their outlook on future directions and trends for DL techniques to further improve diagnosis, reduce health care cost, and optimize ultrasound clinical workflow.     

韶关地区ABO,Rh,MN,P血型分布

目的 掌握韶关地区人群的ABO,Rh,MN,P血型的分布规律,为献血者招募及科学合理库存血液提供理论依据.方法 采用U型96孔微量板对献血者血样进行ABO正反定型及Rh,MN,P血型检测,结果 可疑者用试管法确认.结果 ABO血型基因频率r＞P＞q,表型分布特征为O＞A＞B＞AB;Rh(D)阴性占0.16%;A2亚型在AB型的检出率高于在A型的检出率;MN血型的基因频率m＞n,表型分布特征为MN＞M＞N;P血型的基因频率p2＞p1,表型分布特征为P2＞P1.结论 本地区血型分布特征为O型所占比例最多,且A型多于B型、A2亚型检出率高,Rh(D)阴性率低;应加大O型、A型献血者的招募和保留及相应增加其库存量,特别是要加强Rh(D)阴性献血者的档案管理和Rh(D)阴性血液的保存.     

A Group Randomized Intervention Trial Increases Participation in the School Breakfast Program in 16 Rural High Schools in Minnesota

BackgroundBreakfast consumption is associated with better diet quality and healthier weights, yet many adolescents miss breakfast. Nationally, 17.1% of students participate in the School Breakfast Program (SBP). Only 10% of high school students participate.ObjectiveOur aim was to evaluate an environmental intervention to increase SBP participation in high schools.DesignA group randomized trial was carried out from 2012 to 2015.Participants/settingNinth- and 10th-grade students enrolled in 16 rural schools in Minnesota (median 387 students) were randomized to intervention or control condition.InterventionA school-based intervention that included two key components was implemented over a 12-month period. One component focused on increasing SBP participation by increasing student access to school breakfast through changes in school breakfast service practices (eg, serving breakfast from a grab-n-go cart in the atrium; expanding breakfast service times). The other component focused on promoting school breakfast through student-directed marketing campaigns.Main outcome measureChange in school-level participation in the SBP was assessed between baseline (among ninth and tenth graders) and follow-up (among tenth and eleventh graders). School meal and attendance records were used to assess change in school-level participation rates in the SBP.Statistical analysesThe Wilcoxon test was used for analysis of difference in change in mean SBP participation rate by experimental group.ResultsThe median change in SBP participation rate between baseline and follow-up was 3% (interquartile range=13.5%) among the eight schools in the intervention group and 0.5% (interquartile range=0.7%) among the eight schools in the control group. This difference in change between groups was statistically significant (Wilcoxon test, P=0.03). The intervention effect increased throughout the intervention period, with change in mean SBP participation rate by the end of the school year reaching 10.3% (95% CI 3.0 to 17.6). However, among the intervention schools, the change in mean SBP participation rates was highly variable (range=–0.8% to 24.8%).ConclusionsInterventions designed to improve access to the SBP by reducing environmental and social barriers have potential to increase participation among high school students.