The FHIT gene product: tumor suppressor and genome “caretaker”

The FHIT gene at FRA3B is one of the earliest and most frequently altered genes in the majority of human cancers. It was recently discovered that the FHIT gene is not the most fragile locus in epithelial cells, the cell of origin for most Fhit-negative cancers, eroding support for past claims that deletions at this locus are simply passenger events that are carried along in expanding cancer clones, due to extreme vulnerability to DNA damage rather than to loss of FHIT function. Indeed, recent reports have reconfirmed FHIT as a tumor suppressor gene with roles in apoptosis and prevention of the epithelial–mesenchymal transition. Other recent works have identified a novel role for the FHIT gene product, Fhit, as a genome “caretaker.” Loss of this caretaker function leads to nucleotide imbalance, spontaneous replication stress, and DNA breaks. Because Fhit loss-induced DNA damage is “checkpoint blind,” cells accumulate further DNA damage during subsequent cell cycles, accruing global genome instability that could facilitate oncogenic mutation acquisition and expedite clonal expansion. Loss of Fhit activity therefore induces a mutator phenotype. Evidence for FHIT as a mutator gene is discussed in light of these recent investigations of Fhit loss and subsequent genome instability.     

Eustigmaeus floridensis sp. nov., a new mite species of the genus Eustigmaeus Berlese, 1910 (Acari: Stigmaeidae) from citrus in Florida

Eustigmaeus floridensis sp. nov. is described and illustrated based on female specimens collected from citrus trees in Florida, USA. The new species is closely related to Eustigmaeus arcuata, Eustigmaeus segnis and Eustigmaeus microsegnis, all known to occur in Florida. Eustigmaeus floridensis sp. nov. can be distinguished by larger dimples associated with setae sce, d₂ and e₁ containing at least four or more vacuoles centrally; dorsal body setae broadly lanceolate and feather-like, except c₂, which is slender; anogenital area with striae and one pair of serrated aggenital (ag1) and three pairs of serrated pseudanal (ps_1?3) setae. A key to the Eustigmaeus species known to occur across USA is also provided.     

基于正态分布概率模型的渗滤液回灌影响分析

渗滤液回灌能有效加速填埋场的稳定并处理多余的渗滤液, 而预测回灌过程中渗滤液的运移规律对于合理设置回灌井的间距和数量具有重要的意义. 考虑了垃圾体的非均质性, 建立了垃圾体的渗透系数随空间正态分布变化的概率模型. 利用 COMSOL Multiphysics^® 软件, 首先对单孔隙度的横纵向均质模型和正态分布模型的 渗透系数以及压力水头进行了比较, 其次研究了在横纵向渗透系数比值、回灌速率和回灌时间等不同 影响因素下, 均质模型和正态分布模型的含水率以及横向影响范围的变化规律. 结果表明, 随着横纵向渗透系数比值的增加, 最终在 100 d 时: 均质模型的含水率由 0.609 增加到 0.68, 横向影响范围从4.842 m 增加到 6.79 m; 正态分布模型的含水率由 0.573 增加到 0.610, 横向影响范围从4.097 m 变为 4.04 m. 这说明横纵向渗透系数比值对正态分布模型的含水 率和渗滤液横向影响范围的影响明显高于均质模型. 而当回灌速率和回灌时间相同时, 正态分布模型渗滤液的渗流速度更快, 易于优先达到饱和含水率, 并在短暂的峰值后迅速下降, 且随着回灌速率和回灌时间的增加, 达到饱和含水率和峰值的时间也逐渐增加.     

基于高效液相色谱法的牛黄解毒制剂中胆红素含量测定

利用高效液相色谱法建立牛黄解毒制剂中胆红素的含量测定方法,色谱柱为Agilent Zorbax SB-C18色谱柱,流动相为乙腈—1%冰醋酸(95∶5),检测波长为450 nm.结果显示,胆红素进样量在0.8321~208.032 ng范围内具有良好的线性关系,r=0.9995,牛黄解毒片平均回收率为105.6%,RSD为1.42%,牛黄解毒丸平均回收率为96.2%,RSD为1.83%.结果表明,方法准确、简便,可作为牛黄解毒片及牛黄解毒丸等制剂中胆红素含量的测定方法.     

Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4

P4-ATPases are lipid flippases that catalyze the transport of phospholipids to create membrane phospholipid asymmetry and to initiate the biogenesis of transport vesicles. Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced hypersecretion of proinflammatory cytokines, enhanced MAP kinase signaling and constitutive NF-κB activation. In addition, CDC50A-depleted THP-1 macrophages displayed reduced tolerance to endotoxin. Moreover, endotoxin-induced internalization of TLR4 was strongly reduced and coincided with impaired endosomal MyD88-independent signaling. The phenotype of CDC50A-depleted cells was also induced by separate knockdown of two P4-ATPases, namely ATP8B1 and ATP11A. We conclude that lipid flippases are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4.     

Electric charge in hyperbolic motion: the early history

The study of an electric charge in hyperbolic motion is an important aspect of Minkowski’s geometrical formulation of electrodynamics. In “Space and Time”, his last publication before his premature death, Minkowski gives a brief geometrical recipe for calculating the four-force with which an electric charge acts on another electric charge. The subsequent work of Born, Sommerfeld, Laue, and Pauli filled in the missing derivation details. Here, we bring together these early contributions, in an effort to provide a more modern, accessible, and unified exposition of the early history of the electric charge in hyperbolic motion.