Molecular mechanisms and animal models of spinal muscular atrophy

AbstractSpinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is characterized by the degeneration of spinal motor neurons and muscle atrophy. Although the genetic cause of SMA has been mapped to the Survival Motor Neuron1 (SMN1) gene, mechanisms underlying selective motor neuron degeneration in SMA remain largely unknown. Here we review the latest developments and our current understanding of the molecular mechanisms underlying SMA pathogenesis, focusing on the animal model systems that have been developed, as well as new diagnostic and treatment strategies that have been identified using these model systems. This article is part of a special issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis

Co-contributorship Network and Division of Labor in Individual Scientific Collaborations

Collaborations are pervasive in current science. Collaborations have been studied and encouraged in many disciplines. However, little is known how a team really functions from the detailed division of labor within. In this research, we investigate the patterns of scientific collaboration and division of labor within individual scholarly articles by analyzing their co-contributorship networks. Co-contributorship networks are constructed by performing the one-mode projection of the author-task bipartite networks obtained from 138,787 papers published in PLoS journals. Given a paper, we define three types of contributors: Specialists, Team-players, and Versatiles. Specialists are those who contribute to all their tasks alone; team-players are those who contribute to every task with other collaborators; and versatiles are those who do both. We find that team-players are the majority and they tend to contribute to the five most common tasks as expected, such as "data analysis" and "performing experiments". The specialists and versatiles are more prevalent than expected by a random-graph null model. Versatiles tend to be senior authors associated with funding and supervisions. Specialists are associated with two contrasting roles: the supervising role as team leaders or marginal and specialized contributions.Comment: accepted by JASIS

Exploring links between 2-oxoglutarate-dependent oxygenases and Alzheimer's disease

Hypoxia, that is, an inadequate oxygen supply, is linked to neurodegeneration and patients with cardiovascular disease are prone to Alzheimer's disease (AD). 2-Oxoglutarate and ferrous iron-dependent oxygenases (2OGDD) play a key role in the regulation of oxygen homeostasis by acting as hypoxia sensors. 2OGDD also have roles in collagen biosynthesis, lipid metabolism, nucleic acid repair, and the regulation of transcription and translation. Many biological processes in which the >60 human 2OGDD are involved are altered in AD patient brains, raising the question as to whether 2OGDD are involved in the transition from normal aging to AD. Here we give an overview of human 2OGDD and critically discuss their potential roles in AD, highlighting possible relationships with synapse dysfunction/loss. 2OGDD may regulate neuronal/glial differentiation through enzyme activity-dependent mechanisms and modulation of their activity has potential to protect against synapse loss. Work linking 2OGDD and AD is at an early stage, especially from a therapeutic perspective; we suggest integrated pathology and in vitro discovery research to explore their roles in AD is merited. We hope to help enable long-term research on the roles of 2OGDD and, more generally, oxygen/hypoxia in AD. We also suggest shorter term empirically guided clinical studies concerning the exploration of 2OGDD/oxygen modulators to help maintain synaptic viability are of interest for AD treatment

Effect of Furin inhibitor on lung adenocarcinoma cell growth and metastasis

BACKGROUND: To investigate the mechanisms of lung adenocarcinoma cell metastasis and provide a theoretical basis for the in-depth study of lung adenocarcinoma. METHODS: A549 cells are incubated with different concentrations of Furin inhibitor for indicated times. The proliferation and migration were confirmed with MTT, colony formation, wound Healing and Transwell assayes. Hochest 33342 / PI double staining was used to detect apoptosis. Cell migration and apoptosis associated proteins were analysed by enzyme-linked immunosorbent assay (ELISA) and western blot. RESULTS: We have found that Furin inhibitor play a significant role in inhibition A549 cell growth. And we also found cell migration was inhibited significantly upon Furin inhibitor treatment. CONCLUSION: The proliferration and migration of A549 cell were inhibited by Furin inbitor through down-regulation the expression of migration and apoptosis related proteins