Abnormal neural responses to harmonic syntactic structures in congenital amusia

In music, harmonic syntactic structures are organized hierarchically through local and long‐distance dependencies. This study investigated whether congenital amusia, a neurodevelopmental disorder of pitch perception, is associated with impaired processing of harmonic syntactic structures. For stimuli, we used harmonic sequences containing two phrases, where the first phrase ended with a half cadence and the second with an authentic cadence. In Experiment 1, we manipulated the ending chord of the authentic cadence to be either syntactically regular or irregular based on local dependencies. Sixteen amusics and 16 controls judged the expectedness of these chords while their EEG waveforms were recorded. In comparison to the regular endings, irregular endings elicited an ERAN, an N5, and a late positive component in controls but not in amusics, indicating that amusics were impaired in processing local syntactic dependencies. In Experiment 2, we manipulated the half cadence of the harmonic sequences to either adhere to or violate long‐distance syntactic dependencies. In response to irregular harmonic sequences, an ERAN‐like component and an N5 were elicited in controls but not in amusics, suggesting that amusics were impaired in processing long‐distance syntactic dependencies. Furthermore, for controls, the neural processing of local and long‐distance syntactic dependencies was correlated at the later integration stage but not at the early detection stage. These findings indicate that amusia is associated with impairment in the detection and integration of local and long‐distance syntactic violations. The implications of these findings in terms of hierarchical music‐syntactic processing are discussed.     

CD226 attenuates Treg suppressive capacity via CTLA-4 and TIGIT during EAE

The Cluster of differentiation 226(CD226)/T cell immunoglobulin and immune receptor tyrosine-based inhibitory motif domain (TIGIT) axis plays an important role in the balance of the immune response. A previous study showed that CD226 is involved in CD4+ T cell differentiation and that blocking CD226 may attenuate experimental autoimmune encephalomyelitis (EAE) development. However, the molecular mechanisms underlying this process remain incompletely understood. In this study, it was found that Cd226−/− mice were less susceptible to EAE and that there was less T helper 17(Th17) cell infiltration with higher levels of regulatory cells (Tregs) infiltration in the Cd226−/− EAE mouse central nervous system (CNS) compared with that in the WT EAE mouse CNS. Moreover, the suppressive function of Cd226−/− Tregs was upregulated compared with that of WT Tregs. Furthermore, it was observed that the expression levels of CTLA-4 and TIGIT on Cd226−/− Tregs were higher than those on WT Tregs during EAE in the spleen and CNS. Our results demonstrate a pivotal role for CD226 in attenuating Treg function in EAE that was associated with downregulating the expression levels of CTLA-4 and TIGIT.     

T follicular regulatory cells suppress Tfh-mediated B cell help and synergistically increase IL-10-producing B cells in breast carcinoma

T follicular regulatory (Tfr) cell is a recently discovered subset of T regulatory (Treg) cells. The main function of Tfr cells is thought to suppress germinal cancer reaction and inhibit B cell proliferation and Ig production. However, recent studies demonstrate that Tfr cells may be required for high-affinity Ig formation during acute virus infections. The role of Tfr cells in breast cancer is not thoroughly investigated. In this study, total circulating CD4 T cells were sorted into CD25⁺CXCR5⁻ Treg-like, CD25⁺CXCR5⁺ Tfr-like, and CD25⁻CXCR5⁺ Tfh-like subsets. Data showed that the Tfr-like subset presented intermediate levels of both Foxp3 and Bcl-6, while the Treg-like subset was high in Foxp3 and low in Bcl-6, and the Tfh-like was high in Bcl-6 and low in Foxp3. Of note, the frequencies of Tfr-like and Treg-like cells were significantly elevated in breast cancer (BC) patients than in non-cancer (NC) controls. Tfr-like cells in BC patients also expressed significantly higher levels of Foxp3 than those in NC controls. Neither Treg-like nor Tfr-like cells could support Ig production from naive B cells, while Tfh-like cells potently supported Ig production from naive B cells. Tfr-like cells increased the availability of IL-10, both by directly producing IL-10 and by increasing IL-10 production from B cells. Interestingly, Tfr-like cells increased IL-10 production from B cells synergistically with Tfh cells, but at the same time, significantly reduced Ig production in the Tfh-B cell coculture. These Tfr-mediated effects on Tfh cells were not found in canonical Treg cells. Overall, this study demonstrates several distinctive features in circulating Tfr cells and suggests that Tfr cells may promote the formation of IL-10-producing B cells in BC.

     

Identification and characterization of a novel natural recombinant avian leucosis virus from Chinese indigenous chicken flock

Virus Genes - Avian leukosis virus (ALV) caused tremendous economic losses to poultry industry all over the world, especially in China. One natural recombinant ALV strain, designated as HB2015032,...     

TNF-α/calreticulin dual signaling induced NLRP3 inflammasome activation associated with HuR nucleocytoplasmic shuttling in rheumatoid arthritis

Inflammation Research - The present study was undertaken to validate whether TNF-α and calreticulin (CRT) serve as dual signaling to activate nucleotide-binding oligomerization domain-,...     

Functional characterization of CEP250 variant identified in nonsyndromic retinitis pigmentosa

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C‐Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.     

The effect of xylitol on Streptococcus mutans in children

A study was performed on 91 second-grade students from the Los Angeles Unified School District to test the effects of xylitol chewing gum on Streptococcus mutans in the saliva. Saliva was collected from students and tested for the first time using the new University of California, Los Angeles, monoclonal antibody testing method. Students found to have moderate or high levels of salivary S. mutans were administered four tablets/day of xylitol gum for three weeks. The levels of S. mutans in the saliva of children in the high caries index subgroup decreased by 61.7 percent. Xylitol can be dispensed in a public school setting by school nurses and can be a very safe, efficient and inexpensive preventative measure for children at high risk for dental caries.     

Expression and significance of stromal cell-derived factor-1alpha and its receptor CXCR4 in human dental pulp cells

OBJECTIVE: To investigate the expression of CXCR4 in cultured human dental pulp cells (HDPC) in vitro and the corresponding ligand SDF-1alpha level of HDPC supenatants stimulated by lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha), and to explore the role of SDF-1alpha on the proliferation and the migration of HDPC. METHODS: The expression of CXCR4 in HDPC was detected by immunocytochemistry technique and indirect immunofluorescence technique. The culture supernatants of HDPC were collected after HDPC had been simulated by LPS and TNF-alpha of different concentrations for 48h and then the SDF-1alpha level was assayed by quantitative sandwich ELISA. Meanwhile, the effects of recombinant human SDF-1alpha (rhSDF-1alpha) on the proliferation and the migration of HDPC at different concentrations were observed by MTT and Boyden Chamber Assay. RESULTS: CXCR4 was expressed in cytomembrane of HDPC and SDF-1alpha was secreted into their normal cell supernatants with a concentration of (4513.55 +/- 962.92) ng/L. The secretion of SDF-1alpha was both significantly decreased by stimulation with LPS and TNF-alpha (P < 0.05). In addition, rhSDF-1alpha stimulated the HDPC proliferation at the concentrations of 50, 100, 200 microg/L (P < 0.01) and increased the chemotactic migration of HDPC significantly after 9h's incubation with the concentrations of 50, 100 microg/L (P < 0.05). CONCLUSIONS: SDF-1alpha accelerated the proliferation and the migration of HDPC which expressed CXCR4. SDF-1-CXCR4 axis may play a role in repair of pulp injury.     

新型舌侧磨牙远移器的研制和临床应用

目的 :研制新型舌侧磨牙远移器并运用于临床远移上颌磨牙。方法 :下颌牙弓排列较好的牙性安氏Ⅱ类错牙合病例 2 3例 ,平均年龄 12 .6岁 ,应用我科与杭州西湖生物材料研究所研制的舌侧磨牙远移器 ,采用 15 0 g力远移上颌第一磨牙 ,用头影测量分析上颌磨牙的远移效果。结果 :经过 3 -6个月 ,上颌磨牙平均整体远移 5 .8mm ,前牙覆牙合减少 2 .9mm ,覆盖增加 3 .4mm。远移完成后用Nance腭托将纠正后的安氏I类咬合关系保持 3个月。结论 :舌侧磨牙远移器可以在较少的支抗丧失情况下有效的远中移动上颌磨牙。该装置临床组装容易 ,可减少椅旁操作时间 ,患者易于接受。