[Abstract unavailable

Kabaeva Z, Zhao M, Michele DE. Blebbistatin extends culture life of adult mouse cardiac myocytes and allows efficient and stable transgene expression.

Transgenic mice in which the tetracycline transactivator (tTA) is driven by the forebrain-specific calcium-calmodulindependent kinase IIa promoter (CaMKIIa-tTA mice) are used to study the molecular genetics of many behaviors. These mice can be crossed with other transgenic mice carrying a transgene of interest coupled to the tetracycline-responsive promoter element to produce mice with forebrain-specific expression of the transgene under investigation. The value of using CaMKIIa-tTA mice to study behavior, however, is dependent on the CaMKIIatTA mice themselves lacking a behavioral phenotype with respect to the behaviors being studied. Here we present data that suggest CaMKIIa-tTA mice have a behavioral phenotype distinct from that of their wildtype (WT) littermates. Most strikingly, we find that CaMKIIa-tTA mice, both those with a C57BL/6NTac genetic background (B6-tTA) and those with a 129S6B6F1/Tac hybrid genetic background (F1-tTA), exhibit decreased locomotor activity compared with WT littermates that could be misinterpreted as altered anxiety-like behavior. Despite this impairment, neither B6-tTA nor F1-tTA mice perform differently than their WT littermates in two commonly used learning and memory paradigms -Pavlovian fear conditioning and Morris water maze. Additionally, we find data regarding motor coordination and balance to be mixed: B6-tTA mice, but not F1-tTA mice, exhibit impaired performance on the accelerating rotarod and both perform as well as their WT littermates on the balance beam.

Proteasomes are responsible for the turnover of most cellular proteins, and thus are critical to almost all cellular activities. A substrate entering the proteasome must first bind to a substrate receptor. Substrate receptors can be classified as ubiquitin receptors and non-ubiquitin receptors. The intrinsic ubiquitin receptors, including proteasome regulatory particle base subunits 1, 10 and 13 (Rpn1, Rpn10, and Rpn13), determine the capability of the proteasome to recognize a ubiquitin chain, and thus provide selectivity for the 26S proteasome. However, the non-ubiquitin receptors, including proteasome activator 200 (PA200) and PA28γ, have received great attention due to their remarkable compensatory roles relative to canonical ubiquitin-mediated proteasomal degradation. Herein we review recent advances in understanding the contributions of these substrate receptors to proteasomal degradation, and introduce their substrates and interacting factors. We also provide insights into their biological functions related to spermatogenesis, immune responses, cellular homeostasis, and tumour development. Finally, we summarize advances in developing small-molecule inhibitors of these substrate receptors and discuss their potential as drug targets.

Background Macrophages have been demonstrated to promote the rupture of the atherosclerotic lesion, a primary cause of ischemic events, by modulating the formation of plaque necrosis. We aimed to search the key factors of genetic macrophages in concerns of carotid ruptured plaques.Methods The database of the gene expressed GSE41571 is retrieved from the Gene Expression Omnibus (GEO) to differentially obtain the measured expression genes (DEGs) by tendering the tool usage of GEO2R. The enriched pathways of ontology at DEGs performances with DAVID interacted the constructions of protein to protein networking by the analysis of STRING and Cytoscape software. And also the identified PPI networks in the significance of hub genes module plugged into respective Cytohubba and MCODE Cytoscape.Result A total of 1481 DEGs in macrophages from ruptured and stable carotid atherosclerotic plaques are noticed, by including 568 up-regulation genes and 913 down-regulation genes. The analyzed GO shows a DEGs are mainly involved in protein ubiquitination, endocytosis, mRNA processing, and mitotic cell cycle. KEGG pathway enrichment analysis revealed that some major protein catabolism pathways, including the ubiquitin-proteasome, autophagy, and endocytosis systems, play key roles in the progressive carotid plaque clotting. The genes of the hub in the PPI network included POLR2E , PPP2R1A , HSP90AA1 , and CBL . The modules were mainly associated with ubiquitin-mediated proteolysis, endocytosis, spliceosome, proteasome.Conclusion Our findings offer novel molecular insights into the mechanisms by which macrophages drive formation and vulnerability of plaques. The candidate DEGs and potential biological pathways might be used as diagnostic targets, and facilitate the development of novel macrophage-targeting therapies for unstable atherosclerosis.