Human bone cell cultures: a new model for studying the mechanism of action of calcitonin

An investigation on cell cultures obtained from temporal human bone fragments showed that they provide a suitable model for studying the mechanism involved in calcitonin action on bone cells. Furthermore they demonstrated: a transitory increase in 45Ca uptake that returned to control values ten minutes after the hormone was added; a relation between 45Ca uptake and increased cAMP concentrations when these were measured at the same time intervals; a reproduction of the salmon calcitonin (sCT) effect after incubation of the cultures with either db-cAMP or db-cGMP and inhibition of 45Ca uptake and parallel decrease in cAMP levels with propanol. These results suggest that in human bone cell cultures, sCT acts as a temporary promoter of 45Ca uptake, probably by activating an adenylate-cyclase system through a beta-receptor.     

Computation,wiring, and plasticity in synaptic clusters

Synaptic clusters on dendrites are extraordinarily compact computational building blocks. They contribute to key local computations through biophysical and biochemical signaling that utilizes convergence in space and time as an organizing principle. However, these computations can only arise in very special contexts. Dendritic cluster computations, their highly organized input connectivity, and the mechanisms for their formation are closely linked, yet these have not been analyzed as parts of a single process. Here, we examine these linkages. The sheer density of axonal and dendritic arborizations means that there are far more potential connections (close enough for a spine to reach an axon) than actual ones. We see how dendritic clusters draw upon electrical, chemical, and mechano–chemical signaling to implement the rules for formation of connections and subsequent computations. Crucially, the same mechanisms that underlie their functions also underlie their formation.     

基于网络药理学探讨皂角刺治疗乳痈的作用机制

摘要 目的：基于网络药理学探讨皂角刺治疗乳痈的作用机制。方法：通过建立皂角刺药物靶点数据集、乳痈相关疾病靶点数据集，构建皂角刺治疗急性乳腺炎的蛋白互作（PPI）网络，构建并分析"皂角刺活性成分-潜在靶点-急性乳腺炎"网络。开展基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析，探讨皂角刺治疗乳痈的可能机制。结果：共得到皂角刺活性成分11个，筛选出活性成分所对应的不重复靶点共97个，其中1个活性成分无对应靶点。通过搜集GeneCards 和OMIM数据库，共得到292个急性乳腺炎的相关靶点基因。将疾病靶点基因与药物活性成分所对应的靶点进行比对后，得到10个交集靶点，即皂角刺治疗急性乳腺炎的潜在靶点。皂角刺活性成分按degree值排前3名的依次为槲皮素（quercetin）、漆黄素（fisetin）、山奈酚（kaempferol），其中皂角刺治疗乳痈的靶点包括白细胞介素-6（IL-6）、表皮生长因子受体（EGFR）、酪氨酸激酶受体2（ERBB2）、细胞间黏附分子-1（ICAM1）、雌激素受体1（ESR1）等5个关键靶点，主要涉及乳腺癌疾病通路、TNF信号通路和雌激素信号通路等3条信号通路。结论：皂角刺治疗乳痈的作用机制可能与机体的炎症反应以及雌激素水平变化等密切相关。     

Neonicotinoids Show Selective and Diverse Actions on Their Nicotinic Receptor Targets: Electrophysiology,Molecular Biology,and Receptor Modeling Studies

Neonicotinoid insecticides, which act selectively on insect nicotinic acetylcholine receptors (nAChRs), are used worldwide for insect pest management. Studies that span chemistry, biochemistry, molecular biology, and electrophysiology have contributed to our current understanding of the important physicochemical and structural properties essential for neonicotinoid actions as well as key receptor residues contributing to the high affinity of neonicotinoids for insect nAChRs. Research to date suggests that electrostatic interactions and possibly hydrogen bond formation between neonicotinoids and nAChRs contribute to the selectivity of these chemicals. A rich diversity of neonicotinoid-nAChR interactions has been demonstrated using voltage-clamp electrophysiology. Computational modeling of nAChR-imidacloprid interaction has assisted in the interpretation of these results.     

The Establishment of a HeLa Cell Demonstrating Rapid Mitogen-Activated Protein Kinase Phosphorylation in Response to 1α,25-Dihydroxyvitamin D3 by Stable Transfection of a Chick Skeletal Muscle cDNA Library

1α,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] phosphorylates the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase (MAPK) family, within 30 sec in primary cultured chick skeletal muscle cells. MAPK of HeLa cell lines, which had been stably transfected with a cDNA library derived from mRNA of chick skeletal muscle cells, was also rapidly phosphorylated by 1,25-(OH)₂D₃. These cell lines have the potential to be a good tool for further investigation of rapid non-genomic mechanism activated by 1,25-(OH)₂D₃.     

The Weight of Evidence Does Not Support the Listing of Styrene as “Reasonably Anticipated to be a Human Carcinogen” in NTP's Twelfth Report on Carcinogens

Styrene was listed as “reasonably anticipated to be a human carcinogen” in the twelfth edition of the National Toxicology Program's Report on Carcinogens based on what we contend are erroneous findings of limited evidence of carcinogenicity in humans, sufficient evidence of carcinogenicity in experimental animals, and supporting mechanistic data. The epidemiology studies show no consistent increased incidence of, or mortality from, any type of cancer. In animal studies, increased incidence rates of mostly benign tumors have been observed only in certain strains of one species (mice) and at one tissue site (lung). The lack of concordance of tumor incidence and tumor type among animals (even within the same species) and humans indicates that there has been no particular cancer consistently observed among all available studies. The only plausible mechanism for styrene-induced carcinogenesis—a non-genotoxic mode of action that is specific to the mouse lung—is not relevant to humans. As a whole, the evidence does not support the characterization of styrene as “reasonably anticipated to be a human carcinogen,” and styrene should not be listed in the Report on Carcinogens.