Fibroblast growth factor-hedgehog interdependence during retina regeneration.

The embryonic chick is able to regenerate the retina after it has been removed. We have previously shown that proliferating stem/progenitor cells present in the ciliary body/ciliary marginal zone (CB/CMZ) of the chick eye are responsible for regeneration, which can be induced by ectopic fibroblast growth factor-2 (FGF2) or Sonic hedgehog (Shh). Here, we reveal the mechanisms showing how FGF2 and Shh signaling are interdependent during retina regeneration. If the FGF pathway is inhibited, regeneration stimulated by Shh is inhibited. Likewise, if the Hedgehog pathway is inhibited, regeneration stimulated by FGF2 is inhibited. We examined early signaling events in the CB/CMZ and found that FGF2 or Shh induced a robust Erk phosphorylation during the early stages of retina regeneration. Shh also up-regulated the expression of several members of the FGF signaling pathway. We show that ectopic FGF2 or Shh overexpression increased the number of phosphohistone 3 (PH3)-positive cells in the CB/CMZ and inhibition of either pathway decreased the number of PH3-positive cells. Additionally, both FGF and Hh signaling are required for cell survival in the CB/CMZ, whereas Hh and not FGF signaling plays a role in maintaining the identity of the retinal progenitor population in this region. Combined, our results support a model where the FGF and Hedgehog pathways work together to stimulate retina regeneration.     

液相色谱质谱联用(LC-MS/MS)在天然化学成分分析中的应用Ⅰ.音喷离子化(SSI)与大气压化学离子化(APCI)对利血平的比较分析

报道应用 L C- MS/ MS,采用音喷离子化 (SSI)与大气压化学离子化 (APCI)对利血平的比较分析 ,应用这两种离子化方法比较所得的利血平的标准质谱 (MS)和二级质谱 (MS2 ) ,实验证明两种离子化方法所得结果完全一致     

Maligne Epitheliale Tumoren: Teil I. Pathophysiologie und Klinik

Epithelial skin cancer is a major burden for western societies. In the 21^st century there will be a steady increase in the incidence of these tumors in the elderly population. The article summarizes the pathophysiology of epithelial tumors and gives a systematic outline of the different clinical features of keratinocytic tumors. Furthermore, the article gives an overview of inherited syndromes that predispose to malignant epithelial tumors.     

Mice with a conditional deletion of Talpid3 (KIAA0586) – a model for Joubert syndrome

Joubert syndrome (JS) is a ciliopathy associated with mutations in numerous genes encoding cilia components. TALPID3 encoded by KIAA0856 in man (2700049A03Rik in mouse) is a centrosomal protein essential for the assembly of primary cilia. Mutations in KIAA0856 have been recently identified in JS patients. Herein, we describe a novel mouse JS model with a conditional deletion of the conserved exons 11–12 of Talpid3 in the central nervous system which recapitulates the complete cerebellar phenotype seen in JS. Talpid3 mutant mice exhibit key hallmarks of JS including progressive ataxia, severely hypoplastic cerebellar hemispheres and vermis, together with abnormal decussation of the superior cerebellar peduncles. The Purkinje cell layer is disorganised with abnormal dendritic arborisation. The external granule layer (EGL) is thinner, lacks primary cilia, and has a reduced level of proliferation. Furthermore, we describe novel cellular defects including ectopic clusters of mature granule neurons, and abnormal parallel fibre-derived synapses and disorientation of cells in the EGL. The defective glial scaffold results in abnormal granule cell migration which manifests as ectopic clusters of granule neurons. In addition, we show a reduction in Wnt7a expression suggesting that defects may arise not only from deficiencies in the Hedgehog (Hh) pathway but also due to the additional roles of Talpid3. The Talpid3 conditional knockout mouse is a novel JS model which fully recapitulates the JS cerebellar phenotype. These findings reveal a role for Talpid3 in granule precursor cell migration in the cerebellum (either direct or indirect) which together with defective Hh signalling underlies the JS phenotype. Our findings also illustrate the utility of creating conditional mouse models to assist in unravelling the molecular and cellular mechanisms underlying JS. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Sound production,hearing sensitivity,and in-depth study of the sound-producing muscles in the cowfish (Lactoria cornuta)

The ability to produce sounds has been reported in various Ostraciidae but not deeply studied. In some Ostracion species, two different sound-producing muscles allow these boxfishes to produce two different kinds of sounds in a sequence. This study investigates sound production in another Indo-Pacific species, the longhorn cowfish Lactoria cornuta that also possesses two pairs of sonic muscles associated with the swim bladder: extrinsic sonic muscles (ESMs) and intrinsic sonic muscles (ISMs). The cowfish produces two kinds of sounds called hums and clicks. Hums are made of trains of low amplitude pulses that last for long periods of time, suggesting that they are produced by fatigue-resistant muscles, whereas clicks correspond to shorter sounds with greater amplitude than the hums, suggesting that they result from more powerful contractions. Ultra-structural differences are found between extrinsic and intrinsic sonic muscles. According to features such as long sarcomeres, long I-bands, a high number of mitochondria, and a proliferation of sarcoplasmic reticulum (SR), ESMs would be able to produce fast, strong, and short contractions corresponding to clicks (the shortest sounds with the greatest amplitude). ISMs have the thinnest cells, the smallest number of myofilaments that have long I-bands, the highest volume of mitochondria, and well-developed SR supporting these muscles; these features should generate fast and prolonged contractions that could correspond to the hums that can be produced over long periods of time. A concluding figure shows clear comparisons of the different fibers that were studied in L. cornuta. This study also compared the call features of each sound with the cowfish's hearing ability and supports L. cornuta was more sensitive to frequencies ranging between at least 100 and 400 Hz with thresholds of 128–143 dB re 1 µPa over this range, meaning that they are sensitive to the frequencies produced by conspecifics.