Mouse genetics identifies unique and overlapping functions of fibroblast growth factor receptors in keratinocytes

Fibroblast growth factors (FGFs) are key regulators of tissue development, homeostasis and repair, and abnormal FGF signalling is associated with various human diseases. In human and murine epidermis, FGF receptor 3 (FGFR3) activation causes benign skin tumours, but the consequences of FGFR3 deficiency in this tissue have not been determined. Here, we show that FGFR3 in keratinocytes is dispensable for mouse skin development, homeostasis and wound repair. However, the defect in the epidermal barrier and the resulting inflammatory skin disease that develops in mice lacking FGFR1 and FGFR2 in keratinocytes were further aggravated upon additional loss of FGFR3. This caused fibroblast activation and fibrosis in the FGFR1/FGFR2 double‐knockout mice and even more in mice lacking all three FGFRs, revealing functional redundancy of FGFR3 with FGFR1 and FGFR2 for maintaining the epidermal barrier. Taken together, our study demonstrates that FGFR1, FGFR2 and FGFR3 act together to maintain epidermal integrity and cutaneous homeostasis, with FGFR2 being the dominant receptor.     

Pacer Is a Mediator of mTORC1 and GSK3-TIP60 Signaling in Regulation of Autophagosome Maturation and Lipid Metabolism

1. Download high-res image (230KB)
2. Download full-size image

     

Nonlinear responses of productivity and diversity of alpine meadow communities to degradation北大核心CSCD

Aims The alpine meadow degradation could have profound effects on the grassland productivity. The aim of our study is to clarify the dynamic response of community productivity and species diversity in the process of alpine meadow degradation. Methods In the Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Northern Tibetan Grassland Ecosystem Research Station (Nagqu station), we conducted stages experiments with multiple degradation levels: control, mild degraded meadow, moderate degraded meadow, severe degraded meadow and serious sandy meadow. Important findings The response of aboveground biomass to alpine meadow degradation showed a linear or nonlinear increased response patterns, but the belowground biomass and total biomass decreased nonlinearly. As observed in measurement of aboveground biomass, Margalef index, Simpson index, Shannon-Wiener index and Pielou evenness index also exhibit a nonlinear increased response to degradation. The results of structural equation models showed that belowground biomass has a positive relationship with soil carbon content (p < 0.05) and volume water content (p < 0.1). However, soil nutrient and soil physical properties had no significant impact on aboveground biomass (p < 0.1). Compared with soil physical properties, soil nutrition is an important factor influencing the diversity index. In our study, the nonlinear responses of productivity and diversity of alpine meadow were described by using the multiple levels of degradation in space. The results suggested that aboveground productivity cannot interpret the degree of degradation of alpine meadow, and by contrast, alpine meadow degradation should be measured by the change of plant functional groups, such as edible grasses and poisonous forbs. © 2018 Editorial Office of Chinese Journal of Plant Ecology. All rights reserved.     

生物合成谷胱甘肽种间耦合ATP再生系统的构建

利用重组大肠杆菌Ⅱ 1中的谷胱甘肽合成酶系和面包酵母WSH J7中的ATP生物合成酶系 ,构建了一个以葡萄糖为能源的种间耦合ATP再生系统。经过通透性处理的酵母细胞几乎不能消耗葡萄糖。在反应体系中添加 1mmol/LAMP和 0 0 5mmol/LNADH ,即可启动酵母的酵解途径。提高耦合系统中的葡萄糖浓度 ,可促进GSH的合成。当葡萄糖浓度为 40 0mmol/L时 ,系统内GSH浓度达到 1 0 4mmol/L(3 2 g/L)。Mg2 +缺乏时 ,耦合系统和外加ATP的非耦合系统均不能合成谷胱甘肽。耦合系统中Mg2 +与ATP形成螯合物 ,可能是导致耦合系统中GSH产量较低的原因。在耦合系统中补加Mg2 +,反应 6h时GSH浓度达到 1 4 3mmol/L(4 4g/L)。     

胃伤害性刺激诱导大鼠脑干星形胶质细胞GFAP蛋白表达及其与神经元的关系

研究大鼠在福尔马林诱发胃伤害性刺激时脑干内星形胶质细胞及神经元的变化。应用免疫组织化学三重标记法在脑原位切片同时显示脑干内Fos蛋白,胶质原纤维酸性蛋白（GFAP）,酪氨酸羟化酶（TH）的表达,结果显示：1、在福尔马林诱发胃伤害性刺激后,脑干胶质细胞GFAP表达阳性,并表现出明显的核团或亚核定位特点,在延髓内脏带（MVZ0,中缝大核（RMg),蓝斑（LC）,臂旁外侧核（LPB）,中缝背核（DR）,中脑导水管周围灰质腹外侧区（vlPAG),上丘中灰层（IngSC)等脑区有较多的Fos阳性细胞,而且Fos阳性表达的分布与上述GFAP阳性分布基本一致;2、MVZ,LC,DR,vlPAG等部位有大量Fos及TH双标阳性神经元,周围有密集的GFAP阳性细胞;3、随着刺激后存活时间的变化,GFAP与Fos阳性细胞的反应均经历逐渐升高后又渐降低直至消失的变化。结果表明：上述核团的神经元和星形胶质细胞可能同时参与了内脏痛及其调节过程。     

Scanning by DOVAM-S detects all unique sequence changes in blinded analyses: evidence that the scanning conditions are generic

The [detection of virtually all mutations]-SSCP (DOVAM-S) is a highly sensitive variant of single strand conformation polymorphism (SSCP). Mutations in the factor IX gene were used to find a set of five SSCP conditions that detects virtually all mutations. A blinded analysis of the factor IX gene in patients with hemophilia B detected 82 of 82 unique mutations. Since the method was developed and tested on the factor IX gene, it is possible that the conditions selected work more efficiently in the factor IX gene than in other genes. To test the general applicability of the conditions under which DOVAM-S detected all mutations in this gene, blinded analyses were performed in the human factor VIII and ataxia-telangiectasia (ATM) genes. Segments were amplified individually, combined into groups of 16 to 18 amplified segments and electrophoresed in five different nondenaturing conditions of varying matrices, buffers, temperatures and additives. Blinded analyses were performed in 92 samples from patients with hemophilia A (factor VIII gene) and 19 samples from A-T patients (ATM gene). Combined with an earlier blinded analysis in the factor IX gene, all of the 250 mutations and polymorphisms (180 of which are unique) were detected in both analyses. For two, three and four joint conditions, the average detection frequency ranged from 77%-97%, 91%-100% and 95%-100%, respectively. For each of the genes, one mutation may have been missed if only four conditions were used. With DOVAM-S, approximately 500 kb of autosomal sequence can be scanned in five gels with virtually 100% detection of mutations within the scanned region. The detection of 180 out of 180 unique sequence changes implies that DOVAM-S detects at least 96.5% (P = 0.03) of mutations. Blinded analyses that detect 400 unique sequence changes are required to determine that a scanning method detects at least 98.5% of mutations.     

Biosensors for direct determination of organophosphate pesticides

Direct, selective, rapid and simple determination of organophosphate pesticides has been achieved by integrating organophosphorus hydrolase with electrochemical and opitical transducers. Organophosphorus hydrolase catalyzes the hydrolysis of a wide range of organophosphate compounds, releasing an acid and an alcohol that can be detected directly. This article reviews development, characterization and applications of organophosphorus hydrolase-based potentiometric, amperometric and optical biosensors.     

Modulation of mouse neural crest cell motility by N-cadherin and connexin 43 gap junctions.

Connexin 43 (Cx43alpha1) gap junction has been shown to have an essential role in mediating functional coupling of neural crest cells and in modulating neural crest cell migration. Here, we showed that N-cadherin and wnt1 are required for efficient dye coupling but not for the expression of Cx43alpha1 gap junctions in neural crest cells. Cell motility was found to be altered in the N-cadherin-deficient neural crest cells, but the alterations were different from that elicited by Cx43alpha1 deficiency. In contrast, wnt1-deficient neural crest cells showed no discernible change in cell motility. These observations suggest that dye coupling may not be a good measure of gap junction communication relevant to motility. Alternatively, Cx43alpha1 may serve a novel function in motility. We observed that p120 catenin (p120ctn), an Armadillo protein known to modulate cell motility, is colocalized not only with N-cadherin but also with Cx43alpha1. Moreover, the subcellular distribution of p120ctn was altered with N-cadherin or Cx43alpha1 deficiency. Based on these findings, we propose a model in which Cx43alpha1 and N-cadherin may modulate neural crest cell motility by engaging in a dynamic cross-talk with the cell's locomotory apparatus through p120ctn signaling.