Concerted type I interferon signaling in microglia and neural cells promotes memory impairment associated with amyloid β plaques

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Clinical and genetic characteristics of Stargardt disease in a large Western China cohort: Report 1

Stargardt disease 1 (STGD1) is the most prevalent retinal dystrophy caused by pathogenic biallelic ABCA4 variants. Forty‐two unrelated patients mostly originating from Western China were recruited. Comprehensive ophthalmological examinations, including visual acuity measurements (subjective function), fundus autofluorescence (retinal imaging), and full‐field electroretinography (objective function), were performed. Next‐generation sequencing (target/whole exome) and direct sequencing were conducted. Genotype grouping was performed based on the presence of deleterious variants. The median age of onset/age was 10.0 (5–52)/29.5 (12–72) years, and the median visual acuity in the right/left eye was 1.30 (0.15–2.28)/1.30 (0.15–2.28) in the logarithm of the minimum angle of resolution unit. Ten patients (10/38, 27.0%) showed confined macular dysfunction, and 27 (27/37, 73.7%) had generalized retinal dysfunction. Fifty‐eight pathogenic/likely pathogenic ABCA4 variants, including 14 novel variants, were identified. Eight patients (8/35, 22.8%) harbored multiple deleterious variants, and 17 (17/35, 48.6%) had a single deleterious variant. Significant associations were revealed between subjective functional, retinal imaging, and objective functional groups, identifying a significant genotype–phenotype association. This study illustrates a large phenotypic/genotypic spectrum in a large well‐characterized STGD1 cohort. A distinct genetic background of the Chinese population from the Caucasian population was identified; meanwhile, a genotype–phenotype association was similarly represented.     

Secretory transmembrane potentials in acinar cells from the cat submandibular gland during perfusion with a chloride-free sucrose solution

Summary The cat submandibular gland was perfused with a normal NaCl Locke solution and a chloride-free sucrose solution. The numerical increase in acinar membrane potential (secretory potential) was recorded after intra-arterial injection of acetylcholine.There was no significant difference between the size of the secretory potentials recorded during perfusion with the sucrose solution [23.6 mV±1.4 (n=23)] and the size of those recorded during the control periods [20.6 mV±1.2 (n=24)].The maximal value of the membrane potential after injection of acetylcholine was higher [51.8 mV±2.4 (n=23)] during perfusion with the sucrose solution than during the control periods [44.8 mV±1.8 (n=22)].The results show that a pump transporting chloride into the acinar cells cannot be responsible for the generation of the secretory potentials. The results are best accounted for by assuming that an outward passive transport of potassium, being partly short-circuited by an inward passive sodium transport, is responsible for the change in membrane potential after stimulation with acetylcholine.Supported by the Danish State Research Foundation and Johann and Hanne Weimann's legate.     

脐带穿刺术在胎儿先天性心脏病诊疗中的应用价值

目的探讨脐带穿刺在胎儿先天性心脏病诊疗中的应用价值。方法对34例行脐带穿刺的胎儿先天性心脏病例进行回顾性分析。结果34例均穿刺成功,未发生严重并发症。检出染色体异常6例,宫内巨细胞病毒感染1例。结论脐带穿刺术是一种安全有效改善妊娠结局的产前诊疗技术。     

V180I mutation of the prion protein gene associated with atypical PrP glycosylation

A valine to isoleucine mutation at residue 180 was identified in a French patient with Creutzfeldt-Jakob disease (CJD). The mutation is located in the close vicinity of one of the two N-glycosylation sites of the cellular prion protein (PrP^C). Western blot analysis revealed accumulation in the brain of the pathogenic proteinase K-resistant PrP (PrP^Sc) isoform with the notable absence of the diglycosylated band. The mutant protein expressed in CHO cells was correctly glycosylated, suggesting that the atypical glycosylation pattern of PrP^Sc was not due to the mutation at position 180. These results suggest that the diglycosylated form of the mutant PrP^180I prevents its conversion into the pathogenic mutant form PrP^Sc180I, supporting a central role of N-linked glycan chains in the PrP conversion process.     

Use of class II tetramers for identification of CD4+ T cells

Multivalent MHC class II molecules containing peptide antigens are useful tools for the detection of antigen specific human CD4+ T cells. Tetramers produced by exogenous peptide loading onto empty class II molecules are comparable to tetramers with peptide tethered to the class II chain covalently, but have many practical advantages. Conditions for optimal peptide loading to generate tetramers are discussed and optimal conditions of using tetramers for staining T cells are examined. As the frequency of antigen specific CD4+ T cells in peripheral blood is low, we demonstrate that an in vitro expansion step is effective in detecting low frequency T cells. Two new applications with tetramers, their uses for mapping T cell epitopes and for the detection of low affinity T cells are described. In a clinical setting, potential applications include using these reagents for monitoring disease progression during clinical intervention.