Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice

Introduction

Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals.

Results

Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots.

Conclusions

We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis.     

Non-conventional sources of peptides presented by MHC class I

Effectiveness of immune surveillance of intracellular viruses and bacteria depends upon a functioning antigen presentation pathway that allows infected cells to reveal the presence of an intracellular pathogen. The antigen presentation pathway uses virtually all endogenous polypeptides as a source to produce antigenic peptides that are eventually chaperoned to the cell surface by MHC class I molecules. Intriguingly, MHC I molecules present peptides encoded not only in the primary open reading frames but also those encoded in alternate reading frames. Here, we review recent studies on the generation of cryptic pMHC I. We focus on the immunological significance of cryptic pMHC I, and the novel translational mechanisms that allow production of these antigenic peptides from unconventional sources.     

Novel macrophage polarization model: from gene expression to identification of new anti-inflammatory molecules

Plasticity is a well-known property of macrophages that is controlled by different changes in environmental signals. Macrophage polarization is regarded as a spectrum of activation phenotypes adjusted from one activation extreme, the classic (M1), to the other, the alternative (M2) activation. Here we show, in vitro and in vivo, that both M1 and M2 macrophage phenotypes are tightly coupled to specific patterns of gene expression. Novel M2-associated markers were characterized and identified as genes controlling the extracellular metabolism of ATP to generate pyrophosphates (PPi). Stimulation of M1 macrophages with PPi dampens both NLR and TLR signaling and thus mediates cytokine production. In this context extracellular PPi enhanced the resolution phase of a murine peritonitis model via a decrease in pro-inflammatory cytokine production. Therefore, our study reveals an additional level of plasticity modulating the resolution of inflammation.     

MicroRNA-128 downregulates Bax and induces apoptosis in human embryonic kidney cells

MicroRNAs (miRNAs) are short ~21-nt non-coding RNA molecules that have been shown to regulate a number of biological processes. Previous reports have shown that overexpression of miR-128 in glioma cells inhibited cell proliferation. Literature also suggests that miR-128 negatively regulates prostate cancer cell invasion. Here, we show that overexpression of hsa-miR-128, a brain-enriched microRNA, induces apoptosis in HEK293T cells as elucidated by apoptosis assay, cell cycle changes, loss of mitochondrial membrane potential and multicaspase assay. By in silico analysis, we identified a putative target site within the 3′ untranslated region (UTR) of Bax, a proapoptotic member of the apoptosis pathway. We found that ectopic expression of hsa-miR-128 suppressed a luciferase reporter containing the Bax-3′ UTR and reduced the levels of Bax in HEK293T cells. Taken together, our study demonstrates that overexpression of hsa-miR-128 not only induces apoptosis in HEK293T cells but also is an endogenous regulator of Bax protein.     

Highly reactive oxygen species: detection, formation, and possible functions

The so-called reactive oxygen species (ROS) are defined as oxygen-containing species that are more reactive than O(2) itself, which include hydrogen peroxide and superoxide. Although these are quite stable, they may be converted in the presence of transition metal ions, such as Fe(II), to the highly reactive oxygen species (hROS). hROS may exist as free hydroxyl radicals (HO·), as bound ("crypto") radicals or as Fe(IV)-oxo (ferryl) species and the somewhat less reactive, non-radical species, singlet oxygen. This review outlines the processes by which hROS may be formed, their damaging potential, and the evidence that they might have signaling functions. Since our understanding of the formation and actions of hROS depends on reliable procedures for their detection, particular attention is given to procedures for hROS detection and quantitation and their applicability to in vivo studies.     

The wedge and the vis viva controversy: how concepts of force influenced the practice of early eighteenth-century mechanics

This article discusses the quest for the mechanical advantage of the wedge in the eighteenth century. As a case study, the wedge enlightens our understanding of eighteenth-century mechanics in general and the controversy over “force” or vis viva in particular. In this article, I show that the two different approaches to mechanics, the one that favoured force in terms of velocities and the one that primarily used displacements—known as the ‘Newtonian’ and ‘Leibnizian’ methods, respectively—were not at all on par in their ability to solve the problem of the wedge. In general, only those who used the Leibnizian concept of force or some related notion were able to get to the conventional results. This article thus rebuts the received view that the vis viva controversy was merely a semantic one. Instead, it shows that different understandings of “force” led to real and pragmatic differences in eighteenth-century mechanics.     

GPS单频PPP电离层延迟改正模型探讨

针对电离层延迟会导致GPS单频精密单点定位精度严重缺失的情况,分别探讨了克罗布歇模型、格网模型和历元差分模型,并采用IGS跟踪站数据进行电离层延迟改正。同时根据改正后的单频精密单点定位精度,比较了这三种电离层延迟改正模型的改正效果。结果表明:历元差分模型的改正效果最好,其改正后单频精密单点定位精度可达到厘米级,能较好地符合实际应用要求。     

战区物资调运数学模型研究

如何优化分配,合理调运,及时准确地完成后勤保障任务,是现代战争中战区物资调运面临的重要问题之一.基于运输问题,就现代战争条件下战区物资调运问题的各种情况建立了数学模型.该模型可用于后勤物资保障的决策支持系统及指挥自动化系统,为解决战时后勤保障供应问题提供了新的理论方法和思路.     

非基线对称类信号的基线扣除新算法

在分析了现有基线扣除算法的基础上,根据非基线对称类基线信号的特征提出了一种新的基线扣除算法--基于小波滤波和梯度直方图最佳分割的非基线对称类信号基线扣除新算法.考虑到信号总是存在着噪声,含噪的基线信号梯度值也较大,并且分布无规律,采用了多分辨率小波变换滤波技术.通过合理选择最佳分割阈值门限,算法可精确提取出该类信号的基线.     

引信全电子安全系统程序控制组件设计

全电子安全系统是引信设计的发展方向,程序控制组件是实现引信安全控制的重要部件.介绍了一种引信全电子安全系统程序控制组件的技术要求、基本功能和工作顺序及原理,提出了提高系统可靠性的电路模式和设计原则,同时对程序控制组件的软件设计方法进行了介绍.采用先进的在系统可编程器件,实现系统逻辑功能的集成化、小型化,且具有易于功能扩展、设计升级等优点.