A novel de novo PDE4D gene mutation identified in a Chinese patient with acrodysostosis

Acrodysostosis is an extremely rare disorder at birth, that is, characterized by skeletal dysplasia with short stature and midfacial hypoplasia, which has been reported to be caused by PDE4D and PRKAR1A gene mutations. Here, a Chinese boy with acrodysostosis, ventricular septal defect, and pulmonary hypertension was recruited for our study, and his clinical and biochemical characteristics were analyzed. A novel de novo heterozygous missense mutation (NM_001104631: c.2030A>C, p.Tyr677Ser) of the PDE4D gene was detected by whole exome sequencing and confirmed by Sanger sequencing. The c.2030A>C (p.Tyr677Ser) variant was located in exon 15 of the PDE4D gene, predicted to be damaging by a functional prediction program and shown to be highly conserved among many species. Further functional analysis showed that the p.Tyr677Ser substitution changes the function of the PDE4D protein, affects its subcellular localization in transfected cells, increases PDE4 activity in the regulation of cAMP signaling and affects cell proliferation. Our study identified a novel de novo PDE4D mutation in acrodysostosis of Chinese origin that not only contributes a deeper appreciation of the phenotypic characteristics of patients with PDE4D mutations but also expands the spectrum of PDE4D mutations.     

Quantitative Analysis of the Whole-Body Metabolic Fate of Branched-Chain Amino Acids

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LATS1 K751 acetylation blocks activation of Hippo signalling and switches LATS1 from a tumor suppressor to an oncoprotein

Science China Life Sciences - Large tumor suppressor 1 (LATS1) is the key kinase controlling activation of Hippo signalling pathway. Post-translational modifications of LATS1 modulate its kinase...     

OsRLCK160 contributes to flavonoid accumulation and UV-B tolerance by regulating OsbZIP48 in rice

Science China Life Sciences - Plants produce specialized metabolites to adapt to the ever-changing environments. Flavonoids are antioxidants essential for growth, development, and breeding with...     

Permeation mechanism of a two-state potassium channel

A two-state hopping model was proposed to study the permeation of ion channel. The Nernst equation in equilibrium and the Michaelis-Menten relation in steady state were derived from the two-state kinetic model. The current-voltage relationship obtained in the symmetrical solutions case was linear when the applied potential was less than 100 mV, which met Ohm’s law. The conductance-concentration relationship exhibited the saturation property. Moreover, the characteristic time reaching the steady state of the KcsA channel was also discussed. Translated from Acta Biophysica Sinica, 2005, 21(4): 289–294 [译自: 生物物理学报]     

酶标仪分光光度法在微生物耐性研究上的应用

微生物在环境中的耐性是该微生物在相应环境发挥作用的重要基础。为了获得一种用于微生物耐性分析的快速简便方法,传统平板分离法和酶标仪分光光度法被用于评估其在细菌和链霉菌紫外耐受水平检测中的差异,并分析了酶标仪分光光度法在微生物其他耐性水平检测中的适用性。结果显示,两种检测方法均能体现细菌和链霉菌对紫外线的耐受水平,前者经过稀释、涂布、培养、菌落计数,获得的是菌株在紫外线照射后的存活浓度,而后者经过接种96孔培养板、培养、吸光度检测,获得的是菌株经紫外线照射后的生长曲线,并从生长曲线获知菌株的生长速率、增殖能力等信息。此外,酶标仪分光光度法同样适用于细菌对pH和盐的耐受水平分析,对于链霉菌耐受性分析有一定的适用性。酶标仪法除了能获得与平板分离法相似的耐性水平检测外,还能获得菌株在不同耐性水平上的增殖潜力,且在操作上比平板分离法省时、省力,可用于微生物耐性分析、高通量筛选等研究工作。     

Recent advances in TMEM16A: Structure,function, and disease

TMEM16A (also known as anoctamin 1, ANO1) is the molecular basis of the calcium-activated chloride channels, with ten transmembrane segments. Recently, atomic structures of the transmembrane domains of mouse TMEM16A (mTMEM16A) were determined by single-particle electron cryomicroscopy. This gives us a solid ground to discuss the electrophysiological properties and functions of TMEM16A. TMEM16A is reported to be dually regulated by Ca²⁺ and voltage. In addition, the dysfunction of TMEM16A has been found to be involved in many diseases including cystic fibrosis, various cancers, hypertension, and gastrointestinal motility disorders. TMEM16A is overexpressed in many cancers, including gastrointestinal stromal tumors, gastric cancer, head and neck squamous cell carcinoma (HNSCC), colon cancer, pancreatic ductal adenocarcinoma, and esophageal cancer. Furthermore, overexpression of TMEM16A is related to the occurrence, proliferation, and migration of tumor cells. To date, several studies have shown that many natural compounds and synthetic compounds have regulatory effects on TMEM16A. These small molecule compounds might be novel drugs for the treatment of diseases caused by TMEM16A dysfunction in the future. In addition, recent studies have shown that TMEM16A plays different roles in different diseases through different signal transduction pathways. This review discusses the topology, electrophysiological properties, modulators and functions of TMEM16A in mediates nociception, gastrointestinal dysfunction, hypertension, and cancer and focuses on multiple regulatory mechanisms regarding TMEM16A.