ABSTRACT
In the original publication, the label of Fig. 2C should be read as "GFAP/lectin/DAPI" not "DMP1/GFAP/lectin/DAPI".
ABSTRACT
The rising prevalence of preschool childhood obesity is a global health problem.Statistic data show that the incidence of childhood obesity in China has increased seven times,which threatens health of children and adults.Firstly,childhood obesity may lead to the development of adult obesity.Secondly,it can lead to metabolic disorders and other diseases.There are many factors affecting childhood obesity.It is the result of interaction of genetic and environmental factors,and environmental factors are more important influencing factors of childhood obesity including predisposing genes,obesity of parents,maternal dyslipidemia,maternal gestational diabetes and smoking during pregnancy,intestinal flora,child's diet and physical activity.This review summarizes the influencing factors of childhood obesity in order to provide effective basis for future treatment.
ABSTRACT
Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSC/NPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive "big-data" processing, we report that NSC/NPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSC/NPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Interestingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The Erk/Mapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSC/NPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSC/NPCs and their microenvironment in the context of the aging brain.
Subject(s)
Animals , Mice , Aging , Genetics , Astrocytes , Cell Biology , Metabolism , Brain , Cell Biology , Metabolism , Cell Differentiation , Genetics , Cell Division , Genetics , Cell Proliferation , Genetics , Gene Expression Regulation , Genetics , Neural Stem Cells , Metabolism , Single-Cell Analysis , Stem Cells , Cell Biology , Metabolism , Transcriptome , GeneticsABSTRACT
The blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation. However, detailed molecular players involved in formation of BBB are not completely known. Dentin matrix protein 1 (DMP1)-proteoglycan (PG), which is known to be involved in mineralization of bones and dentin, is also expressed in soft tissues including brain with unknown functions. In the present study, we reported that DMP1-PG was expressed in brain astrocytes and enriched in BBB units. The only glycosylation site of DMP1 is serine89 (S89) in the N-terminal domain of the protein in mouse. Mutant mice with DMP1 point mutations changing S89 to glycine (S89G), which completely eradicated glycosylation of the protein, demonstrated severe BBB disruption. Another breed of DMP1 mutant mice, which lacked the C-terminal domain of DMP1, manifested normal BBB function. The polarity of S89G-DMP1 astrocytes was disrupted and cell-cell adhesion was loosened. Through a battery of analyses, we found that DMP1 glycosylation was critically required for astrocyte maturation both in vitro and in vivo. S89G-DMP1 mutant astrocytes failed to express aquaporin 4 and had reduced laminin and ZO1 expression, which resulted in disruption of BBB. Interestingly, overexpression of wild-type DMP1-PG in mouse brain driven by the nestin promoter elevated laminin and ZO1 expression beyond wild type levels and could effectively resisted intravenous mannitol-induced BBB reversible opening. Taken together, our study not only revealed a novel element, i.e., DMP1-PG, that regulated BBB formation, but also assigned a new function to DMP1-PG.
Subject(s)
Animals , Female , Male , Mice , Astrocytes , Cell Biology , Metabolism , Blood-Brain Barrier , Cell Biology , Metabolism , Cells, Cultured , Extracellular Matrix Proteins , Genetics , Metabolism , Glycosylation , Proteoglycans , Metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
<p><b>OBJECTIVE</b>To analyze the effect of small interfering RNA (siRNA) targeting mouse epididymis-specific colipase-like (meClps) gene on mouse sperm mobility.</p><p><b>METHODS</b>The eukaryotic expression vector pDsRed2.0-C1-meClps was constructed and transfected into NIH-3T3 cells, and the protein expression was detected with anti-meClps serum. Three interfering sequences targeting meClps (RNAi-251, 224 and 286) were inserted into lentiviral vectors pRNAT-U6.2/lenti, which were co-transfected with pDsRed2.0-C1-meClps into NIH-3T3 cells. The RNA interfering efficiency was confirmed by semi-quantitative PCR and Western blotting. The lentivirus, packed with the lentiviral vector with the highest interfering efficiency, was injected into the caput tissues of mouse epididymis, and its effect on sperm mobility of the cauda epididymis was evaluated.</p><p><b>RESULTS</b>All the 3 lentiviral RNAi vectors targeting meClps could inhibit the mRNA and protein expressions of meClps, among which pRNAT-U6.2/lenti-RNAi-251 had the highest interfering efficiency. The lentivirus packed with pRNAT-U6.2/lenti-RNAi-251 significantly reduced the path velocity of cauda sperm after injection into the caput epididymis of the mice (P<0.05).</p><p><b>CONCLUSION</b>Knock-down meClps expression by lentiviral-mediated RNA interference can lower sperm mobility of mice.</p>