Histamine synergistically promotes bFGF‐induced angiogenesis by enhancing VEGF production via H1 receptor

Histamine, a major mediator present in mast cells that is released into the extracellular milieu upon degranulation, is well known to possess a wide range of biological activities in several classic physiological and pathological processes. However, whether and how it participates in angiogenesis remains obscure. In the present study, we observed its direct and synergistic action with basic fibroblast growth factor (bFGF), an important inducer of angiogenesis, on in vitro angiogenesis models of endothelial cells. Data showed that histamine (0.1, 1, 10 µM) itself was absent of direct effects on the processes of angiogenesis, including the proliferation, migration, and tube formation of endothelial cells. Nevertheless, it could concentration‐dependently enhance bFGF‐induced angiogenesis as well as production of vascular endothelial growth factor (VEGF) from endothelial cells. The synergistic effect of histamine on VEGF production could be reversed by pretreatments with diphenhydramine (H1‐receptor antagonist), SB203580 (selective p38 mitogen‐activated protein kinase (MAPK) inhibitor) and L ‐NAME (nitric oxide synthase (NOS) inhibitor), but not with cimetidine (H2‐receptor antagonist) and indomethacin (cyclooxygenase (COX) inhibitor). Moreover, histamine could augment bFGF‐incuced phosphorylation and degradation of IκBα, a key factor accounting for the activation and translocation of nuclear factor κB (NF‐κB) in endothelial cells. These findings indicated that histamine was able to synergistically augment bFGF‐induced angiogenesis, and this action was linked to VEGF production through H1‐receptor and the activation of endothelial nitric oxide synthase (eNOS), p38 MAPK, and IκBα in endothelial cells. J. Cell. Biochem. 114: 1009–1019, 2013. © 2012 Wiley Periodicals, Inc.     

Effect of mesenchymal stem cells on inhibiting airway remodeling and airway inflammation in chronic asthma

Previous studies proved that bone marrow‐derived mesenchymal stem cells (BMSCs) could improve a variety of immune‐mediated disease by its immunomodulatory properties. In this study, we investigated the effect on airway remodeling and airway inflammation by administrating BMSCs in chronic asthmatic mice. Forty‐eight female BALB/c mice were randomly distributed into PBS group, BMSCs treatment group, BMSCs control group, and asthmatic group. The levels of cytokine and immunoglobulin in serum and bronchoalveolar lavage fluid were detected by enzyme‐linked immunosorbent assay. The number of CD4⁺CD25⁺regulatory T cells and morphometric analysis was determined by flow cytometry, hematoxylin‐eosin, immunofluorescence staining, periodic‐acid Schiff, and masson staining, respectively. We found that airway remodeling and airway inflammation were evident in asthmatic mice. Moreover, low level of IL‐12 and high levels of IL‐13, IL‐4, OVA‐specific IgG1, IgE, and IgG2a and the fewer number of CD4⁺CD25⁺regulatory T cells were present in asthmatic group. However, transplantation of BMSCs significantly decreased airway inflammation and airway remodeling and level of IL‐4, OVA‐specific IgE, and OVA‐specific IgG1, but elevated level of IL‐12 and the number of CD4 + CD25 + regulatory T cells in asthma (P < 0.05). However, BMSCs did not contribute to lung regeneration and had no significant effect on levels of IL‐10, IFN‐Y, and IL‐13. In our study, BMSCs engraftment prohibited airway inflammation and airway remodeling in chronic asthmatic group. The beneficial effect of BMSCs might involved the modulation imbalance cytokine toward a new balance Th1–Th2 profiles and up‐regulation of protective CD4 + CD25 + regulatory T cells in asthma, but not contribution to lung regeneration. J. Cell. Biochem. 114: 1595–1605, 2013. © 2013 Wiley Periodicals, Inc.     

Microsatellite genetic variation in the Chinese endemic Eucommia ulmoides (Eucommiaceae): implications for conservation

Eucommia ulmoides, a traditional Chinese medicinal plant, is endangered as a consequence of long‐term and widespread harvest in the late 20th century. It has been widely cultivated as a source of herbal medicine and for use in the organic chemical industry in China. In this study, eight microsatellite markers were applied to investigate genetic diversity in E. ulmoides. Three hundred individuals from one semi‐wild population and nine cultivated populations across its main production area were collected. A high level of genetic diversity at population levels (H_E = 0.716) was observed. The highly outcrossed mating system, high longevity of E. ulmoides and seed admixture may be responsible for high genetic variation within populations. A genetic bottleneck was observed in one population. Populations were only slightly differentiated from one another (F_ST = 0.063); this was also supported by AMOVA, which revealed that 94.05% of the total variation resided within populations. This is probably attributable to long‐distance gene flow mediated by the exchange of seeds by local farmers. Implications of these results for the conservation of genetic resources of E. ulmoides are discussed. © 2013 The Linnean Society of London, Botanical Journal of the Linnean Society, 2013, 173 , 775–785.     

Saving face: the emotional costs of the Asian immigrant family myth

Access to resources through ethnic group membership is often presumed to affect the intensity of ethnic identification. We examine this premise using survey data on three ethnic groups in Mauritius: Creoles, Hindus, and Muslims. Two key findings emerge from our research. First, access to material resources explains only a modest proportion of total variation in ethnic identification within each group. Second, the resources that affect ethnic identification differ significantly across groups. Access to political goods through group membership affects Hindu identification but is unrelated to ethnic identification among Creoles or Muslims. Conversely, access to economic goods affects Creole and Muslim identification but has no effect on Hindu identification. Explaining these group differences leads us beyond a basic means–ends instrumentalist model to identify conditions that likely mediate the relationship between individual interests and collective identification including the divisibility of economic goods relative to political goods in Mauritius.     

Potentilla jiaozishanensis sp. nov. (sect. Leptostylae,Rosaceae) from southwest China

Potentilla jiaozishanensis, a distinct new species of Rosaceae from Yunnan, China, is described and illustrated. Morphologically, it is closely related to P. stenophylla var. stenophylla but clearly differs from the latter by its bidentate leaflets, lanceolate epicalyx‐segments that are longer than the sepals, villose ovaries and achenes. Moreover, the pollen grains of P. jiaozishanensis are markedly different from those of P. stenophylla var. stenophylla in size and shape. The newly described species is endemic to the Jiaozishan Mountains, southwest China.     

Dynamic microtubules produce an asymmetric E-cadherin–Bazooka complex to maintain segment boundaries

Distributing junctional components around the cell periphery is key for epithelial tissue morphogenesis and homeostasis. We discovered that positioning of dynamic microtubules controls the asymmetric accumulation of E-cadherin. Microtubules are oriented preferentially along the dorso-ventral axis in Drosophila melanogaster embryonic epidermal cells, and thus more frequently contact E-cadherin at dorso-ventral cell–cell borders. This inhibits RhoGEF2, reducing membrane recruitment of Rho-kinase, and increasing a specific E-cadherin pool that is mobile when assayed by fluorescence recovery after photobleaching. This mobile E-cadherin is complexed with Bazooka/Par-3, which in turn is required for normal levels of mobile E-cadherin. Mobile E-cadherin–Bazooka prevents formation of multicellular rosette structures and cell motility across the segment border in Drosophila embryos. Altogether, the combined action of dynamic microtubules and Rho signaling determines the level and asymmetric distribution of a mobile E-cadherin–Bazooka complex, which regulates cell behavior during the generation of a patterned epithelium.     

PI3K and Notch signal pathways coordinately regulate the activation and proliferation of T lymphocytes in asthma

AimsIn the present study, we determined whether Phosphoinositide 3-kinase (PI3K) and Notch signal pathways are involved in the expression of cyclinD1, cyclinA and p27kip1 which were key molecules in controlling cell cycling from CD4⁺ T lymphocyte in animal model of asthma.Main methodsOvalbumin (OVA) sensitized murine model of asthma was used to investigate the expression of cyclin D1, cyclin A, and p27kip1 by splenic CD4⁺ T lymphocytes. We further observed the effect of specific inhibitor of PI3K(LY294002) and specific inhibitor of Notch(DAPT) on the proliferation of such CD4⁺ T lymphocytes.Key findingsWe found that the expression of cyclinD1 and cyclinA was upregulated at both protein and mRNA levels in asthma group while p27kip1 was down-regulated. Both LY294002 and DAPT inhibit the proliferation of CD4⁺ T lymphocytes in a time- and dose-dependent manner. Furthermore, LY294002 and DAPT have additive effect in down-regulation of cyclinD1 and upregulation of p27kip1. An upregulation of cyclinA, although not statistically significant, was also observed.SignificanceThese data suggested that PI3K signal pathway and Notch signal pathway may coordinately regulate the cell proliferation and differentiation processes through up-regulating cyclinD1 and down-regulating p27kip1 of CD4⁺ T lymphocytes.     

Deep Whole-Genome Sequencing of 100 Southeast Asian Malays

Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies.