Changes in microRNA expression induced by rabies virus infection in mouse brains

MicroRNAs (miRNAs) are small RNA (≈22 nt) molecules expressed endogenously in cells. They are involved in the regulation of gene expression. Recently, evidence has shown that cellular miRNAs have key regulatory roles in virus-host interactions. The rabies virus (RABV) causes a fatal infection of the central nervous systems (CNS) of warm-blooded animals, yet its pathogenesis remains poorly understood. To gain more insight into the pathogenesis of RABV, a miRNA microarray was performed as part of an investigation of changes in host miRNA expression in the brains of mice infected with RABV. The results showed that RABV infection induced modulation of the expression of sixteen miRNA molecules. These data were verified by real-time PCR. Functional analysis showed the differentially expressed miRNAs to be involved in many immune-related signaling pathways, such as the RIG-I-like receptor signaling pathway, JAK-STAT signaling pathway, chemokine signaling pathway, T-cell receptor signaling pathway, MAPK signaling pathway, leukocyte transendothelial migration, and natural killer cell mediated cytotoxicity. The predicted expression levels of the target genes of these modulated miRNAs correlated with measurements of gene expression measured by DNA microarray and qRT-PCR.     

腺苷酸活化蛋白激酶与肿瘤的靶向治疗

腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)是一种多方面调节细胞功能的能量感受器.AMPK可以由多种途径被激活,主要通过LKB1-AMPK-mTOR及相关通路,调节代谢、调控细胞周期.AMPK存在于肿瘤细胞中,可以抑制细胞增殖,与肿瘤的靶向治疗有着密切的关系.     

Sustaining program effectiveness after implementation: The case of the self-management of well-being group intervention for older adults

ObjectiveThe Self-Management of Well-being (SMW) group intervention for older women was implemented in health and social care. Our aim was to assess whether effects of the SMW intervention were comparable with the original randomized controlled trial (RCT). Furthermore, we investigated threats to effectiveness, such as participant adherence, group reached, and program fidelity.MethodsIn the implementation study (IMP) 287 and RCT 142 women participated. We compared scores on self-management ability and well-being of the IMP and RCT. For adherence, drop-out rates and session attendance were compared. Regarding reach, we compared participants’ baseline characteristics. Professionals completed questions regarding program fidelity.ResultsNo significant differences were found on effect outcomes and adherence between IMP and RCT (all p ≥ 0.135). Intervention effect sizes were equal (0.47–0.59). IMP participants were significantly less lonely and more likely to be married, but had lower well-being. Most professionals followed the protocol, with only minimal deviations.ConclusionThe effectiveness of the SMW group intervention was reproduced after implementation, with similar participant adherence, minimal changes in the group reached, and high program fidelity.Practice implicationsThe SMW group intervention can be transferred to health and social care without loss of effectiveness. Implementation at a larger scale is warranted.     

Deafferentation and pointing with visual double-step perturbations

 The capability of reprogramming movement responses following changes in the visual goal has been studied through the double-step paradigm. These studies have shown that: (a) continuous internal feedback-loops correct unconsciously the dynamic errors throughout the movement; (b) proprioceptive information and/or the efference copy have a privileged status among central processes, insuring on-line regulation of the initial motor commands; and (c) generation of the motor program starts after target presentation, and is continuously updated in the direction of the current internal representation of the target, at least until the onset of hand movement. This main corrective process of the initial program appears to be basically independent of visual reafference from the moving hand. However, the agreement with the possibility of a visuomotor loop, based on the comparison of the new updated representation of the target position and on the information from the moving hand, has not determined whether the correcting process is proprioceptive feedback dependent, or whether internal feedback-loops (efferent copies) are responsible for quick corrections of unfolding motor responses. To answer this question, the present experiment investigated the pointing behavior of a deafferented subject, using a double-step paradigm under various conditions of visual feedback and movement initiation. Overall, the present study (a) clearly showed the capacity of the motor system to modify and correct erroneous trajectories on the mere basis of internal feedback-loops and (b) emphasized the crucial role played by the target jump/arm triggering delay and the importance of the eye efferent copy for providing information about the spatial goal of the movement. Received: 10 July 1998 / Accepted: 23 November 1998     

The middle range of the number line orients attention to the left side of visual space

Mental representation of numbers is believed to be spatial in nature, with small numbers occupying the left and large numbers the right side of a putative mental number line. Consistent with this, presentation of numbers from the low and high ends of the mental number line induces covert shifts of spatial attention to the left and right side of visual space, respectively. However, the effect of the presentation of the middle range (containing numbers below and above the midpoint) of the number line on visual perception has so far not been studied. Here we show in two experiments, using a line bisection task and a simple target detection task, that processing of middle-range numbers affects allocation of visuospatial attention in a similar way as processing of small numbers, with attention shifted to the left side of space. We suggest that this pattern of results arises due to “anchoring” heuristics that participants use in number processing.     

Discovery of novel non-synonymous SNP variants in 988 candidate genes from 6 centenarians by target capture and next-generation sequencing

Despite evidence of a substantial genetic component, the genetic factors that underlie longevity in humans remain to be identified. Previous genome-wide linkage and association studies have not found strong evidence for the contribution of common variants besides the APOE gene, suggesting the role of rare variants in human longevity. To discover rare variants that might contribute to longevity, we selected 988 candidate genes and performed a pilot study to identify novel non-synonymous variants in 6 Ashkenazi Jewish centenarians older than 105. Our candidate genes act in pathways implicated in aging and longevity, including neurodegeneration, cognitive function, lipid metabolism, DNA repair, and genome maintenance. By implementing custom-designed Agilent SureSelect target capture and next-generation sequencing, we discovered a total of 89 novel non-synonymous SNPs (nsSNPs) and validated 51 nsSNPs by iPLEX MassArray assays. Genotyping analysis of these novel SNPs in 410 Ashkenazi Jewish controls and 390 centenarians showed significant enrichment (5.3 fold, p = 0.02) of the p.Y318C variant in PMS2 and significant depletion (7.5 fold, p = 0.04) of the p.V465A variant in GABRR3 in centenarians compared to controls. Our study presents the potential of targeted next-generation sequencing for discovery of rare but functional genetic variation which may lead to exceptional longevity in humans.     

低频电磁场与细胞信号系统

１引言在２０世纪,环境中的低频电磁场的强度已经大大增强。环境中的低频电磁场主要起源于电的传送,电的分配及电的使用。近年来的研究表明低频电磁场的生物效应是明显的。ＬｉｂｏｆｆＡ在１９８４年报道了交变电磁场对ＤＮＡ合成的影响［１］。ＳｍｉｔｈＳ．等在１９...     

胆管癌免疫检查点抑制剂治疗研究进展

胆管癌是一种罕见的恶性肿瘤,总体预后较差。根治性手术治疗是目前唯一可使早期胆管癌病人获得长期生存的策略。对于多数晚期胆管癌病人,系统治疗成为主要手段,但目前可用于治疗胆管癌的一线药物选择有限,疗效有限。近年来,免疫检查点抑制剂等免疫治疗策略利用宿主免疫系统进行有效的抗肿瘤反应,在多种实体肿瘤中取得令人鼓舞的结果。笔者回...     

选择性靶动脉栓塞在骶骨肿瘤切除术中的价值

目的 探讨和评估选择性靶动脉栓塞骶骨肿瘤后对外科切除肿瘤的价值和方法。方法 运用Seldinger技术，对9例骶骨肿瘤患者进行肿瘤供血动脉及肿瘤内血管全部彻底栓塞，栓塞材料应用明胶海绵，栓塞后1周内行手术切除术。结果 彻底的术前栓塞手术中失血量明显减少，9例骶骨肿瘤均得到彻底切除，平均失血量为1090ml。术后平均随访15个月，未见肿瘤局部复发。结论 骶骨肿瘤切除术前选择性靶动脉栓塞可有效减少术中出血，有利于肿瘤的彻底切除，为顺利切除骶骨肿瘤提供了有价值的方法。