Regulation of antibody effector functions through IgG Fc N-glycosylation

Immunoglobulin gamma (IgG) antibodies are key effector proteins of the immune system. They recognize antigens with high specificity and are indispensable for immunological memory following pathogen exposure or vaccination. The constant, crystallizable fragment (Fc) of IgG molecules mediates antibody effector functions such as complement-dependent cytotoxicity, antibody-mediated cellular cytotoxicity, and antibody-dependent cell-mediated phagocytosis. These functions are regulated by a single N-linked, biantennary glycan of the heavy chain, which resides just below the hinge region, and the presence of specific sugar moieties on the glycan has profound implications on IgG effector functions. Emerging knowledge of how Fc glycans contribute to IgG structure and functions has opened new avenues for the therapeutic exploitation of defined antibody glycoforms in the treatment of cancer and autoimmune diseases. Here, we review recent advances in understanding proinflammatory IgG effector functions and their regulation by Fc glycans.     

Retinoic acid regulates avian lung branching through a molecular network

Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development. The current report characterizes, for the first time, the expression pattern of RA signaling members (stra6, raldh2, raldh3, cyp26a1, rarα, and rarβ) and potential RA downstream targets (sox2, sox9, meis1, meis2, tgfβ2, and id2) by in situ hybridization. In the attempt of unveiling the role of RA in chick lung branching, in vitro lung explants were performed. Supplementation studies revealed that RA stimulates lung branching in a dose-dependent manner. Moreover, the expression levels of cyp26a1, sox2, sox9, rarβ, meis2, hoxb5, tgfβ2, id2, fgf10, fgfr2, and shh were evaluated after RA treatment to disclose a putative molecular network underlying RA effect. In situ hybridization analysis showed that RA is able to alter cyp26a1, sox9, tgfβ2, and id2 spatial distribution; to increase rarβ, meis2, and hoxb5 expression levels; and has a very modest effect on sox2, fgf10, fgfr2, and shh expression levels. Overall, these findings support a role for RA in the proximal–distal patterning and branching morphogenesis of the avian lung and reveal intricate molecular interactions that ultimately orchestrate branching morphogenesis.     

Periostin in inflammation and allergy

We found for the first time that IL-4 and IL-13, signature type 2 cytokines, are able to induce periostin expression. We and others have subsequently shown that periostin is highly expressed in chronic inflammatory diseases―asthma, atopic dermatitis, eosinophilc chronic sinusitis/chronic rhinosinusitis with nasal polyp, and allergic conjunctivitis—and that periostin plays important roles in the pathogenesis of these diseases. The epithelial/mesenchymal interaction via periostin is important for the onset of allergic inflammation, in which periostin derived from fibroblasts acts on epithelial cells or fibroblasts, activating their NF-κB. Moreover, the immune cell/non-immune cell interaction via periostin may be also involved. Now the significance of periostin has been expanded into other inflammatory or fibrotic diseases such as scleroderma and pulmonary fibrosis. The cross-talk of periostin with TGF-β or pro-inflammatory cytokines is important for the underlying mechanism of these diseases. Because of its pathogenic importance and broad expression, diagnostics or therapeutic drugs can be potentially developed to target periostin as a means of treating these diseases.     

Melatonin and mitochondrial function during ischemia/reperfusion injury

Ischemia/reperfusion (IR) injury occurs in many organs and tissues, and contributes to morbidity and mortality worldwide. Melatonin, an endogenously produced indolamine, provides a strong defense against IR injury. Mitochondrion, an organelle for ATP production and a decider for cell fate, has been validated to be a crucial target for melatonin to exert its protection against IR injury. In this review, we first clarify the mechanisms underlying mitochondrial dysfunction during IR and melatonin’s protection of mitochondria under this condition. Thereafter, special focus is placed on the protective actions of melatonin against IR injury in brain, heart, liver, and others. Finally, we explore several potential future directions of research in this area. Collectively, the information compiled here will serve as a comprehensive reference for the actions of melatonin in IR injury identified to date and will hopefully aid in the design of future research and increase the potential of melatonin as a therapeutic agent.     

Greenhouse Effects in Global Warming based on Analogical Reasoning

Using an analogy in science and everyday life is a double-edged sword because they are accompanied by alternative ideas, in addition to scientific concepts. Schools and public education explain global warming by making a common analogy between this phenomenon and greenhouse effects (Chen in Philos Cogn Sci 105–114, 2012). Unfortunately, this analogy sometimes produces various incorrect explanatory mental models. To construct a correct understanding of global warming, it is necessary: first, to investigate the attributes of analogical reasoning; second, to understand these features by restructuring the greenhouse analogy; and third, to explore the problems and benefits of the greenhouse analogy. The characteristics of relations, rather than objects, must be mapped according to the principle of systematicity, but the public tends to preserve the attributes of the base domain, which is mapped relatively easily. In conclusion, certain facets of the prevailing greenhouse analogy cause a distorted public view of climate change. We must use the greenhouse analogy and yet simultaneously emphasize the relations and attributes highlighted and hidden in the analogy during evaluation.     

Love and Realism

In this reply I try to show that, contrary to Milberry’s apparent assertion, the general intellect of the multitude does not have the explanatory robustness she accredits to it (following both Virno and the Hardt and Negri of the Empire trilogy). Digital network technologies are currently overwhelmingly effective in proletarianizing and disempowering the cognitariat and only an active technopolitics of deproletarianization could reverse this hegemonic situation. In my response to Verbeek, I attempt to correct his misinterpretation (shared by Milberry) of the Stieglerian approach as being dialectical in nature and show that, far from reinstating the humanist dichotomy between human beings and technologies, my analysis assumes their original, albeit fundamentally ambiguous and even ‘uncanny’ [unheimlich] interconnection. I conclude with pointing out some implications of this view for a ‘really realistic’ political theory of technology.     

The Struggle for Technology: Towards a Realistic Political Theory of Technology

Pieter Lemmens’ neo-Marxist approach to technology urges us to rethink how to do political philosophy of technology. First, Lemmens’ high level of abstraction raises the question of how empirically informed a political theory of technology needs to be. Second, his dialectical focus on a “struggle” between humans and technologies reveals the limits of neo-Marxism. Political philosophy of technology needs to return “to the things themselves”. The political significance of technologies cannot be reduced to its origins in systems of production or social organization, but requires study at the micro-level, where technologies help to shape engagement, interaction, power, and social awareness.     

FGM圆板考虑面内振动的动态响应

为研究考虑面内振动时FGM圆板的动态响应,首先基于经典板理论,同时考虑横向振动和面内振动,并利用Hamilton原理推导出轴对称情况下功能梯度材料圆薄板线性自由振动的控制方程。采用打靶法对无量纲控制方程进行数值求解,并将方程退化为一般均质板,求解其固有频率,得到了与相关文献非常接近的结果。对具体问题的数值结果进行对比分析,结果表明,面内振动会影响FGM圆板振动频率大小,忽略面内振动的影响会过高估计FGM板的频率。     

某型重机枪身管的多物理场耦合分析

为了研究具有不同厚度铬涂层的某型重机枪身管在高温、高压、高速火药流体作用下的温度场和应力场,采用基于多物理场耦合程序接口MpCCI联合结构计算软件Abaqus和流体计算软件Fluent进行耦合计算的方法,对涂层厚度分别为0.28mm、0.35mm、0.41mm的身管进行流-固-热多物理场耦合仿真计算。通过计算得到了不同铬涂层厚度下身管应力和温度的分布规律。结果表明,借助MpCCI联合Abaqus和Fluent进行多物理场耦合计算的方法是可行的;随着涂层厚度的增加身管内壁的温度和应力依次降低,但在涂层与身管结合处的集中应力逐渐增大。结论对身管的结构设计和寿命预测有一定的指导意义。     

介质流向对截止阀流场和流阻特性的影响

为探索介质流向对截止阀内部流场和流阻特性的影响,应用SOLIDWORKS软件建立截止阀的三维模型。使用Fluent软件中的有限元法和标准k-ε湍流模型,在不同开度的情况下,采用数值模拟分析的方法,研究不同介质流向下截止阀的流场和流阻特性,分析阀体内部的速度和压力分布规律。结果表明:在两种不同的流向下,阀门的流通能力相差较小;在小开度时,介质高进低出时能够减小阀门的压力损失,在流通高压介质的情况下,高进低出的流向能够极大的减小阀门的关闭力。流场的分析为截止阀的结构设计和优化提供参考。