VEGF +936C/T and +460C/T gene polymorphisms and oral cancer risk: a meta-analysis

Many studies have examined the association between the VEGF +936C/T (rs833061) and +460C/T (rs3025039) gene polymorphisms and oral cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, we performed a meta-analysis. The PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched for case–control studies that were published up to January 2013. Data were extracted and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. Ultimately, six studies were included, comprising 1006 oral cancer cases and 1016 controls. Overall, the pooled OR for VEGF +936 T allele carriers (TC + TT) versus the wild-type homozygotes (CC) was 1.28 (95 % CI 1.04–1.58; P = 0.228 for heterogeneity), the pooled OR for TT versus CC was 1.64 (95 % CI 1.34–1.98; P = 0.315 for heterogeneity), and the pooled OR for the T allele versus the C allele was 1.42 (95 % CI 1.22–1.76; P = 0.286 for heterogeneity). In the stratified analysis by ethnicity, significant risks were found among Caucasians but not Asians. However, there were no associations between VEGF +460C/T and oral cancer risk in only two of the included studies. In conclusion, this meta-analysis demonstrates that the VEGF +936 T allele may be associated with an increased risk of oral cancer, especially among Caucasian populations.     

Association between PIN1 promoter polymorphisms and risk of nasopharyngeal carcinoma

Peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1) plays an important role in cell transformation and oncogenesis. Association between PIN1 promoter polymorphisms and cancer risk was reported in several cancers. This study aimed to evaluate the association between two single nucleotide polymorphisms (SNPs, ?667T>C, rs2233679 and ?842G>C, rs2233678) on PIN1 promoter and risk of nasopharyngeal carcinoma (NPC). The two SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism in a total of 334 native Chinese subjects consisting of 178 cases and 156 controls. The results indicated that the ?667CT heterozygote and ?667CC homozygote exhibited a significantly decreased risk of nasopharyngeal carcinoma when compared with ?667TT homozygote (OR = 0.639, 95 % CI = 0.452–0.903, p = 0.011 for ?667CT; and OR = 0.441, 95 % CI = 0.213–0.915, p = 0.038 for ?667CC, respectively). In the ?842G>C polymorphism, compared with ?842GG homozygote, only ?842CG heterozygote but not ?842CC homozygote had a significantly decreased risk of nasopharyngeal carcinoma (OR = 0.465, 95 % CI = 0.249–0.871, p = 0.010). Genotype in the two SNPs in patients showed no significant associations with the clinicopathologic features examined. Our study showed that the minor genotypes of PIN1 promoter (?667CT, ?667CC and ?842CG) were associated with decreased risk of NPC in a Chinese population, suggested that PIN1 promoter polymorphisms might play an important role in NPC carcinogenesis.     

Protein–protein interaction and SNP analysis in intraductal papillary mucinous neoplasm

Intraductal papillary mucinous neoplasm (IPMN) is a type of tumor that grows within the pancreatic ducts. It is a progress from hyperplasia to intraductal adenoma (IPMA), to noninvasive carcinoma, and ultimately to invasive carcinoma (IPMC). The objective of this study was to explore the molecular mechanism of the progression from IPMA to IPMC. By using the GSE19650 affymetrix microarray data accessible from Gene Expression Omnibus (GEO) database, we first identified the differentially expressed genes (DEGs) between IPMA and IPMC, followed by the protein–protein interaction and single-nucleotide polymorphism (SNP) analysis of the DEGs. Our study identified thousands of DEGs which involved regulation of cell cycle and apoptosis in this progression from IPMA to IPMC. Protein–protein interaction network construction found that MYC, IL6ST, NR3C1, CREBBP, GATA1 and LRP1 might play an important role in the progression. Furthermore, the SNP analysis confirmed the association between BRAC1 and pancreas cancer. In conclusion, our data provide a comprehensive bioinformatics analysis of genes and pathways which may be involved in the progression of IPMN from IPMA to IPMC.     

First Report of Dieback of Mango Caused by Fusarium decemcellulare in China

During 2009–2011, a dieback disease of mango (Mangifera indica) has recently emerged on mango trees in Panzhihua City, Sichuan province of China. The disease is characterized by large irregular brown‐coloured speckles on the petioles and twigs, vascular necrosis and dry leaves and complete twig mortality. Fusarium species were isolated repeatedly from the infected petioles and twigs. The species was identified as Fusarium decemcellulare Brick based on morphology and sequence analysis of Translation Elongation Factor‐1alpha (TEF‐1α) gene. Koch's postulates were fulfilled by pathogenicity tests on potted mango seedlings. To our knowledge, this is the first record of dieback on mango caused by F. decemcellulare in China.     

The mysterious origins of coronary vessels

The origin of the coronary vessels remains a mystery. Here we discuss recent studies that address this puzzle, including new work by Tian et al. recently published in Cell Research.We face a growing epidemic of coronary vascular disease. Better understanding of the development of this unique vascular system will allow development of new treatment strategies. The origin of the coronary vessels has been a longstanding mystery. Classical anatomists proposed several potential sources for coronary vessels: the proepicardium (PE), the liver, the sinus venosus (SV) and the endocardium (Figure 1). Several recent reports have used sophisticated molecular and cell biological approaches to address this mystery, but have come to apparently contradictory conclusions. Tian et al.¹ use new lineage-tracing approaches to solve this puzzle, leading to new insights and new questions.Open in a separate windowFigure 1Diagram of E9.5 mouse embryo illustrating the proposed sources of coronary ECs. sv, sinus venosus; pe, proepicardium; li, liver primordium; v, ventricle; a, atrium.Initial studies in avian embryos, based on clonal retroviral labeling, dye labeling and quail-chick interspecies chimeras, indicated that coronary vascular smooth muscle and endothelial cells (vSMCs and ECs) derive from extracardiac sources. Most studies pinpointed the PE, a transient embryonic outgrowth of the septum transversum, as the cell source². PE cells transit to the heart, where they undergo an epithelial to mesenchymal transition (EMT). Based on these data, the predominant view from the early 1990s through the mid-2000s was that coronary vessels formed through a vasculogenic process from PE-derived mesenchymal cells. However, not all studies were in agreement. For example, Poelmann et al.³ reached a different conclusion and identified the nearby liver primoridium as the cell source. This study concluded that ECs and precursors formed small vessels that initially connected to the SV and then to subepicardial cells overlying the myocardium, which subsequently penetrated the myocardium to form the coronary vessels.The mainstream view of coronary artery formation from PE-derived ECs has been re-evaluated over the past decade through the use of Cre-LoxP genetic lineage-tracing approaches in mice^4,5,6,7. Several different mouse Cre lines that label populations within the PE were developed. Although these lines generally robustly label coronary vSMCs, they label a low fraction of coronary ECs (generally < 10%). Superficially, this suggests a divergence between avian and mammalian systems, but detailed comparison suggests that the results may be entirely consistent: the avian data indicate that some coronary ECs arise from the PE but the fraction of ECs that originate from PE was not determined. Both avian and murine studies could therefore be interpreted to suggest that a small fraction of coronary ECs arise from PE. A recent study further pointed out that PE contains heterogeneous cell populations, and some of these subpopulations (e.g., Sema3d⁺) contribute more robustly to coronary ECs than others (e.g., Tbx18⁺)⁷. Some lineages traced from the PE also contributed to ECs in the SV and endocardium, providing alternative routes whereby PE may give rise to coronary ECs. This study did not define the fraction of coronary ECs labeled by any of these subpopulations, therefore an estimate of the extent that these additional PE subpopulations contribute to coronary ECs is currently unavailable.Red-Horse et al.⁸ recently re-examined the endothelial lining of the SV as the origin of coronary ECs. Consistent with the study by Poelmann et al.³ in avian embryos, Red-Horse et al. observed that the first vessels of the heart tube connect to the SV. Elegant clonal labeling experiments using an EC-specific, tamoxifen-induced Cre (Cdh5-CreERT2) showed that labeling of single cells around E7.5 yielded descendant “clones” of ECs. At this point in development, PE cells do not express CDH5 and therefore these clones do not originate from this source. Most clones (74%) included SV ECs. However, its relationships with extracardiac structures, such as the liver primordium, were not investigated. Interestingly, SV ECs express venous markers, but descendant ECs belong to arterial and venous lineages. Based on these data, Red-Horse et al. concluded that most coronary ECs arise by angiogenic sprouting of SV ECs onto the developing heart, where they dedifferentiate, proliferate, form the coronary plexus, and subsequently redifferentiate into coronary arteries, capillaries and veins. While these data are compelling, to what extent this mechanism contributes to the coronary vasculature cannot be determined from this study.Wu et al.⁹ used a different lineage-tracing strategy to study coronary vessel origins and reached a different conclusion. This study was based on both constitutive and inducible Cre alleles driven by endocardium-specific Nfatc1 regulatory elements, which do not label PE, epicardium or SV prior to E10.5. By clonal analysis, Nfatc1-lineage cells differentiated to both artery and veins. Quantitative analysis showed that Nfatc1-labeled ECs form most intramyocardial coronary ECs (predominantly arteries) and a minority of supepicardial coronary ECs (predominantly veins). The clonal analysis of Red-Horse et al.⁸ also identified endocardial budding as a source of coronary vessels. Their data showed that fewer clones (24%) contained endocardial cells compared to SV cells, leading to the conclusion that endocardium makes a lesser contribution compared to the SV. However, this assumes equivalent labeling by Cdh5-CreERT2 under conditions where tamoxifen levels were limited. The frequency of endocardial cell labeling under these conditions may have been lower, for example if endocardial cells express lower levels of CreERT2.Tian et al.¹ studied coronary vessel development using Apln^CreERT2, a new lineage-tracing tool that selectively labels newly forming vessels but not established vessels or endocardium. Well-executed morphological and lineage-tracing experiments provide strong evidence that Apln^CreERT2 pulse activation at E11.5 labels nearly all subepicardial and intramyocardial coronary vessels of the ventricular free walls. Pulse labeling at this time labeled only rare ECs in the ventricular septum, suggesting that these vessels arise from ECs that express Apln^CreERT2 only after E11.5 and not from labeled ECs already present in the ventricular free walls. The endocardium appears to be an excellent candidate source for ECs in the ventricular septum. Clonal labeling experiments further demonstrated that at the single cell level, Apln⁺ ECs, named subepicardial ECs, retain the potential to differentiate into both arteries and veins.What is the relationship between subepicardial ECs and the proposed sites of origin for coronary ECs (PE, SV, endocardium, and liver primordium)? Using in vitro organ culture, Tian et al.¹ show that these cells are generated from the SV and subsequently extend onto the ventricles. Ventricles (containing ventricular endocardium) did not generate these cells in this system, leading the authors to conclude that they arise from the SV. However, the in vitro system does not yield robust coronary vessel formation, and it is entirely possible that certain developmental processes, such as endocardial budding or epicardial differentiation, are inactive under these conditions. Thus, we can conclude that some Apln⁺ ECs arise from SV, but the possibility of their origin also from other sources such as endocardium, PE, or liver primordium cannot be excluded.In summary, coronary ECs arise from multiple sources, and the balance between sources likely differs by anatomic region. While many studies on coronary vessel origins appear to reach conflicting conclusions, careful considerations of the experimental approaches and their limitations suggest models consistent with most published data. For instance, perhaps endocardial budding generates most intramyocardial coronaries, while angiogenic sprouting from the SV generates most subepicardial coronaries and a subset of intramyocardial coronaries. PE cells may contribute to a fraction of both EC populations, and give rise to most of the supporting smooth muscle cells. The Apln⁺ subepicardial ECs may represent a key common intermediate formed from all of these sources. Evaluating the contribution of each proposed cell source to this population will be important to understand the origins and growth patterns of coronary vessels. Further progress will depend on carefully quantitating the contribution of various EC sources to coronary vessel subtypes stratified by anatomic location.Understanding the origins of coronary vessels has implications for therapeutic strategies for coronary artery diseases, as each cell source suggests distinct mechanisms. For instance, SV angiogenic sprouting would direct us to investigate the signals that induce SV EC dedifferentiation and then redifferentiation into artery and vein ECs. PE-derived ECs might be induced by enhancing adult epicardial EMT and EC differentiation, while an endocardial EC source would prompt us to understand the signals that regulate the endocardial budding and differentiation process. The work of Tian et al. and the many other studies summarized herein are yielding insights into the mystery of coronary vessel origins. Solving this puzzle will yield rich rewards.     

ALDH2 protects against stroke by clearing 4-HNE

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that metabolizes ethanol and toxic aldehydes such as 4-hydroxy-2-nonenal (4-HNE). Using an unbiased proteomic search, we identified ALDH2 deficiency in stroke-prone spontaneously hypertensive rats (SHR-SP) as compared with spontaneously hypertensive rats (SHR). We concluded the causative role of ALDH2 deficiency in neuronal injury as overexpression or activation of ALDH2 conferred neuroprotection by clearing 4-HNE in in vitro studies. Further, ALDH2-knockdown rats revealed the absence of neuroprotective effects of PKCε. Moderate ethanol administration that is known to exert protection against stroke was shown to enhance the detoxification of 4-HNE, and to protect against ischemic cerebral injury through the PKCε-ALDH2 pathway. In SHR-SP, serum 4-HNE level was persistently elevated and correlated inversely with the lifespan. The role of 4-HNE in stroke in humans was also suggested by persistent elevation of its plasma levels for at least 6 months after stroke. Lastly, we observed that 21 of 1 242 subjects followed for 8 years who developed stroke had higher initial plasma 4-HNE levels than those who did not develop stroke. These findings suggest that activation of the ALDH2 pathway may serve as a useful index in the identification of stroke-prone subjects, and the ALDH2 pathway may be a potential target of therapeutic intervention in stroke.     

伞形科棱子芹属花粉形态特征及其演化意义

采用光学显微镜及扫描电子显微镜观察了国产棱子芹属（Pleurospermum Hoffm．）13个种类的花粉形态特征。结果显示：供试13个种类的花粉粒可分为近菱形、近圆形、椭圆形、近长方形和超长方形5种类型。极轴长度（P）17．1—27．1μm,多为20～25μm;赤道轴长度（E）12．5—19．3μm,多为13．6～18．6μm;PIE值为1．2—2．0,多为1．2—1．5。极面观通常为三角形或近卵状三角形,少数种类为近圆形,仅1种（太白棱子芹Pgiraldii Diels）为三裂圆形;赤道面观多为近菱形、近圆形或椭圆形,少数种类为近长方形,仅1种（太白棱子芹）为超长方形。萌发孔为三沟孔,大多数种类为角萌发孔,仅云南棱子芹（P．yunnanense Franch．）和太白棱子芹为边萌发孔;沟长达两极或几达两极。赤道区的纹饰密集且多样,大体可分为短皱脑纹、颗粒状纹和细网纹3类,其中仅岩生棱子芹[Prupestre（Popov）K．T．FuetY．C．Ho]具细网纹;极区纹饰与赤道区常不一致,多为穴状网纹或纹饰不清晰。依据观察结果,讨论了棱子芹属在伞形科中的演化地位以及属内各种类间的演化关系,并结合宏观形态特征及果实解剖特征探讨了棱子芹（PcamtschaticumHoffm．）、太白棱子芹和矮棱子芹（P．nanumFranch．）的分类问题。     

Sustained PU.1 Levels Balance Cell-Cycle Regulators to Prevent Exhaustion of Adult Hematopoietic Stem Cells

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Highlights? PU.1 prevents hematopoietic stem cell (HSC) exhaustion ? PU.1 is a master regulator of cell-cycle genes in HSCs ? PU.1 binding mediates chromosome looping in HSCs ? Positive autoregulation via a ?14 kb enhancer sustains PU.1 levels in HSCs     

Asiaontsira gen. nov., a new tropical genus of the subfamily Doryctinae (Hymenoptera: Braconidae) from Vietnam and South‐East China

A new genus, Asiaontsira gen. nov., and two new species, A. cucphuongi sp. nov. (type species) and A. cantonica sp. nov., are described from tropical and subtropical areas of South‐East China and North Vietnam. This genus is compared to the closely related Australian Ontsirospathius Belokobylskij, Iqbal and Austin, 2004 as well as the similar and almost cosmopolitan genus Ontsira Cameron, 1900. A key to both species of Asiaontsira gen. nov. is provided.     

Asia1型口蹄疫病毒受体结合位点多样性

摘要：【目的】产甘油假丝酵母作为一株优良高产甘油菌株,已成功应用于工业生产15年。近年来由于产甘油假丝酵母染色体倍性尚不明确,限制了对其进行遗传改造的研究进展,因而我们对产甘油假丝酵母染色体倍性研究,分析确定其染色体倍性。【方法】选用酿酒酵母细胞进行生孢,制备酿酒酵母单倍体细胞作对照,并选用热带假丝酵母作为二倍体酵母细胞对照,利用血球计数板得到热带假丝酵母、产甘油假丝酵母、单倍体及二倍体酿酒酵母细胞数,提取染色体,通过二苯胺检测法测定DNA含量。由于在相同紫外照射条件下单倍体细胞比二倍体细胞更容易死亡,因