Regulation of photoreceptor phosphodiesterase (PDE6) by phosphorylation of its inhibitory gamma subunit re-evaluated.

Phosphorylation of the inhibitory gamma subunit (Pgamma) of rod cGMP phosphodiesterase (PDE6) has been reported to turn off visual excitation without the requirement for inactivation of the photoreceptor G-protein transducin. We evaluated the significance of Pgamma phosphorylation for PDE6 regulation by preparing Pgamma stoichiometrically phosphorylated at Thr(22) or at Thr(35). Phosphorylation of Pgamma at either residue caused a minor decrease--not the previously reported increase--in the ability of Pgamma to inhibit catalysis at the active site of purified PDE6 catalytic dimers. Likewise, Pgamma phosphorylation had little effect on its potency to inhibit transducin-activated PDE6 depleted of its endogenous Pgamma subunits. The strength of Pgamma interaction with the regulatory GAF domain of PDE6 was reduced severalfold upon Pgamma phosphorylation at Thr(22) (but not Thr(35)), as judged by allosteric changes in cGMP binding to these noncatalytic sites on the enzyme (Mou, H., and Cote, R. H. (2001) J. Biol. Chem. 276, 27527-27534). In contrast, the effects of Pgamma phosphorylation on its interactions with activated transducin were much more pronounced. Phosphorylation of Pgamma at either Thr(22) or Thr(35) greatly diminished its ability to bind activated transducin, consistent with earlier work. In situ phosphorylation of Pgamma by endogenous rod outer segment kinases was enhanced severalfold upon light activation, but only approximately 10% of the endogenous Pgamma was phosphorylated. This is attributed to Pgamma being a poor substrate for protein kinases when associated with the PDE6 holoenzyme. We conclude that, contrary to previous reports, Pgamma phosphorylation at either Thr(22) or Thr(35) modestly weakens its direct interactions with PDE6. However, Pgamma phosphorylation subsequent to its dissociation from PDE6 is likely to abolish its binding to activated transducin and may serve to make phosphorylated Pgamma available to regulate other signal transduction pathways (e.g. mitogen-activated protein kinase; Wan, K. F., Sambi, B. S., Frame, M., Tate, R., and Pyne, N. J. (2001) J. Biol. Chem. 276, 37802-37808) in photoreceptor cells.     

Developmental History Provides a Roadmap for the Emergence of Tumor Plasticity

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Structure-activity relationship study of a series of caspase inhibitors containing γ-amino acid moiety for treatment of cholestatic liver disease

A series of caspase inhibitors containing γ-amino acid moiety have been synthesized. A systemic study on their structure-activity relationship of anti-apoptotic cellular activity is presented. These efforts led to the discovery of compound 20o as a potent caspase inhibitor, which demonstrated preclinical ameliorating total bilirubin efficacy with a significantly improved pharmacokinetic profile.     

Length–weight relationships of three small fish species caught in the Yarlung Zangbo River basin,China

Length–weight relationships (LWRs) were determined for three small fish species, Glaridoglanis andersonii (Day, 1870), Glyptosternum maculatum (Regan, 1905) and Pseudecheneis sulcatus (Mc‐Clelland, 1842) from the Yarlung Zangbo River basin, China. A total of 285 specimens were collected from the Yarlung Zangbo River in May and October 2017(frequency of sampling during the study period: once per month).The specimens were caught with fishing gear including drifting gillnets (nets: 10 × 1.0 m; mesh size: 3.0 cm) and shrimp cages (nets: 4.0 × 0.5 × 0.4 m; mesh size: 0.5 cm).     

Combined surgical-orthodontic treatment of patients with cleidocranial dysplasia: case report and review of the literature

Objectives

To study the present treatment situation and investigate a better orthodontic approach for patients with cleidocranial dysplasia (CCD) through systematically reviewing the published cases and to conclude the surgical-orthodontic treatment experience of cleidocranial dysplasia.

Methods

A comprehensive search for studies published through to April 10, 2018 was conducted using the Pubmed, Web of Science, and Embase databases. The CCD cases treated with the approach combining surgical exposure and orthodontic treatment were concluded.

Results

Eight papers and 9 finished cases were included to be compared with the present case. The age of cases ranged from 9 to 28?years. Clearing the way of eruption path in early age can facilitate the spontaneous eruption of impacted teeth. For adults, combined surgical-orthodontic treatment can achieve a nearly complete dentition and stable occlusal contact, but it is time consuming and needs surgical assistance. The combination of orthognathic surgery can reduce the difficulty of orthodontic treatment and treatment duration, as well as achieve a better facial profile.

Conclusion

Surgical exposure combined with orthodontic traction is an effective treatment for patient with CCD. Patient’s age, demand, economic circumstances, and status of permanent dentition should be considered when making treatment plan.

     

重金属累积对泽兰实蝇幼虫生长发育和保护酶的影响

为了弄清重金属通过寄主植物紫茎泽兰累积后对专性寄生天敌泽兰实蝇的生理影响,采用模拟Cd~(2+)、Pb~(2+)或Zn~(2+)污染的土壤培养法胁迫紫茎泽兰,让泽兰实蝇低龄幼虫寄生取食,利用原子吸收分光光度法测定泽兰实蝇老熟幼虫中Cd~(2+)、Pb~(2+)或Zn~(2+)的含量,同时测定分析泽兰实蝇老熟幼虫的体长、鲜重、能量物质和保护酶的变化。结果表明,实验处理的Cd~(2+)、Pb~(2+)或Zn~(2+)均可通过紫茎泽兰传递并累积到泽兰实蝇老熟幼虫体内,引起老熟幼虫一系列生理变化:长度和鲜重降低;总糖、总蛋白和总脂的含量降低,相应的热量值也降低;超氧化物歧化酶(SOD)、过氧化物酶(POD)和过氧化氢酶(CAT)等保护酶的活性降低。本研究为进一步阐明重金属污染对食物链各环节的影响提供了重要的理论依据。     

番茄（Lycopersicon）的化感作用研究

采用室内生测、室外盆栽和水培相结合的研究方法,以多种受体品种来探讨番茄 的化感作用．结果表明,番茄植物不仅具有自毒作用,番茄植株的水提液对黄瓜、萝卜、生 菜、白菜、包心菜的幼苗生长均有显著的抑制作用;番茄植株的挥发物对黄瓜的生长具有 明显的抑制作用,但对绿豆、白菜、生菜及番茄自身的幼苗生长则无明显的影响;番茄移苗 后４０ ｄ之内,其根分泌物对黄瓜生长有明显抑制作用,但对生菜作用不明显认为自毒作 用是造成番茄连作障碍的原因之一,指出番茄种植应采用轮作方式,水培或大棚种植番茄 时,应避免与黄瓜间种．     

Identification of lanthionine synthase C-like protein-1 as a prominent glutathione binding protein expressed in the mammalian central nervous system

Proteomic experiments were performed to identify novel glutathione (GSH) binding proteins expressed in the mammalian central nervous system. Bovine brain lysate was affinity purified using an immobilized glutathione-Sepharose column. Proteins that bound the immobilized glutathione were eluted with free glutathione and identified by one- and two-dimensional electrophoresis coupled with mass spectrometric analysis of tryptic fragments. Major proteins purified by this technique were glutathione S-transferase-mu (GST-mu) and GST-pi and lanthionine synthase C-like protein-1 (LanCL1). LanCL1 is a mammalian homologue of a prokaryotic enzyme responsible for the synthesis of thioether (lanthionine) cross-links within nascent polypeptide chains, yielding macrocyclic proteins with potent microbicidal activity. An antibody against LanCL1 was generated and applied to immunochemical studies of spinal cord tissue from SOD1G93A transgenic mice, a model for amyotrophic lateral sclerosis (ALS), wherein LanCL1 expression was found to be increased at presymptomatic stages of the disease. These results indicate LanCL1 is a glutathione binding protein possibly significant to neurodegenerative disease.