Chromosome elimination and chromosome pairing in tetraploid hybrids of Hordeum vulgare × H. bulbosum

Summary The C₀ tetraploid counterparts of diploid hybrids of Hordeum vulgare × H. bulbosum were meiotically analysed, and were found to be chromosomally less stable than the same genotypes had been as diploids. The 14 bulbosum chromosomes present in the tetraploid cytotypes were probably eliminated as pairs rather than randomly or one genome at the time. Development of the vulgare and bulbosum genomes was asynchronous in some hybrids, the bulbosum chromosomes appearing less advanced than the vulgare chromosomes in the same cell. This appeared to reduce pairing between bulbosum homologues and also suppressed homoeologous pairing.     

Fertile progeny of a hybridization between soybean [Glycine max (L.) Merr.] and G. tomentella Hayata

Summary A colchicine-doubled F₁ hybrid (2n=118) of a cross between PI 360841 (Glycine max) (2n=40) x PI 378708 (G. tomentella) (2n=78), propagated by shoot cuttings since January 1984, produced approximately 100 F₂ seed during October 1988. One-fourth of the F₂ plants or their F₃ progeny have been analyzed for chromosome number, pollen viability, pubescence tip morphology, seed coat color, and isoenzyme variation. Without exception, all plants evaluated possessed the chromosome number of the G. max parent (2n=40). Most F₂ plants demonstrated a high level of fertility, although 2 of 24 plants had low pollen viability and had large numbers of fleshy pods. One F₂ plant possessed sharp pubescence tip morphology, whereas all others were blunt-tipped. All evaluated F₂ and F₃ plants expressed the malate dehydrogenase and diaphorase isoenzyme patterns of the G. max parent and the endopeptidase isoenzyme pattern of the G. tomentella parent. Mobility variants were observed among progeny for the isoenzymes phosphoglucomutase, aconitase, and phosphoglucoisomerase. This study suggests that the G. Tomentella chromosome complement has been eliminated after genetic exchange and/or modification has taken place between the genomes.Journal Paper No. J-13776 of the Iowa Agriculture and Home Economics Experiment Station, Ames, IA, USA, Project 2763     

Mitochondrial and calcium perturbations in rat CNS neurons induce calpain-cleavage of Parkin: Phosphatase inhibition stabilizes pSer65Parkin reducing its calpain-cleavage

Mitochondrial impairment and calcium (Ca⁺⁺) dyshomeostasis are associated with Parkinson's disease (PD). When intracellular ATP levels are lowered, Ca⁺⁺-ATPase pumps are impaired causing cytoplasmic Ca⁺⁺ to be elevated and calpain activation. Little is known about the effect of calpain activation on Parkin integrity. To address this gap, we examined the effects of mitochondrial inhibitors [oligomycin (Oligo), antimycin and rotenone] on endogenous Parkin integrity in rat midbrain and cerebral cortical cultures. All drugs induced calpain-cleavage of Parkin to ~36.9/43.6 kDa fragments. In contrast, treatment with the proinflammatory prostaglandin J2 (PGJ2) and the proteasome inhibitor epoxomicin induced caspase-cleavage of Parkin to fragments of a different size, previously shown by others to be triggered by apoptosis. Calpain-cleaved Parkin was enriched in neuronal mitochondrial fractions. Pre-treatment with the phosphatase inhibitor okadaic acid prior to Oligo-treatment, stabilized full-length Parkin phosphorylated at Ser⁶⁵, and reduced calpain-cleavage of Parkin. Treatment with the Ca⁺⁺ ionophore A23187, which facilitates Ca⁺⁺ transport across the plasma membrane, mimicked the effect of Oligo by inducing calpain-cleavage of Parkin. Removing extracellular Ca⁺⁺ from the media prevented oligomycin- and ionophore-induced calpain-cleavage of Parkin. Computational analysis predicted that calpain-cleavage of Parkin liberates its UbL domain. The phosphagen cyclocreatine moderately mitigated Parkin cleavage by calpain. Moreover, the pituitary adenylate cyclase activating peptide (PACAP27), which stimulates cAMP production, prevented caspase but not calpain-cleavage of Parkin. Overall, our data support a link between Parkin phosphorylation and its cleavage by calpain. This mechanism reflects the impact of mitochondrial impairment and Ca⁺⁺-dyshomeostasis on Parkin integrity and could influence PD pathogenesis.     

长半衰期药物无清洗期时的生物等效性研究*

摘要目的：探讨长半衰期药物（t1/2>24 h）在无清洗期时生物等效性研究中的AUC 和Cmax 的计算,通过无清洗期的实验数据推 算出正常清洗期的数据。方法：利用SPSS软件,建立二室模型口服药物在无清洗期时的半衰期为100 小时的生物等效性模型,通 过优化AUC和Cmax 的计算方法,降低药物残留对第二周期药物浓度的影响,进而增加AUC 和Cmax 的计算的精确性,最后用 较精确的方法推算出正常清洗期的AUC 和Cmax,利用精确的数据进行生物等效性的进一步验证。结果：在无清洗期的状态下, 取样时间在大于0.8 个半衰期时,平均值法计算的AUC 和Cmax 的结果误差小于5 %,变异系数小于25 %,较为精确,生物等效 性研究进一步验证了这一观点。结论：在无清洗期的情况下,生物等效性研究最小的采样时间为0.8 个半衰期。     

曼氏血吸虫发育过程中的基因组DNA变异

曼氏血吸虫（Ｓｃｈｉｓｔｏｓｏｍａｍａｎｓｏｎｉ）和日本血吸虫（Ｓ．ｊａｐｏｎｉｃｕｍ）成虫和曼氏血吸虫尾蚴基因组ＤＡＮ经限制性内切酶ＢａｍＨＩ消化后,分别与＾３２ｐ－ｄＣＴＰ标记的来源于核糖体ＤＮＡ的ＰＳＭＨＣＲ５、ＰＳＭＨＣＲ４ＰＳＭ８８９探针杂交,曼我血吸虫尾蚴和成虫在ＰＳＭＨＣＲ４杂交带型的１．６－２．８ｋｂ之间,存在有明显不同的次杂带;而ＰＳＭＨＣＲ５和ＰＳＭ８８９的杂交带型,无明显差异     

Identification of gene expression profiles and key genes in subchondral bone of osteoarthritis using weighted gene coexpression network analysis

Osteoarthritis (OA) significantly influences the quality life of people around the world. It is urgent to find an effective way to understand the genetic etiology of OA. We used weighted gene coexpression network analysis (WGCNA) to explore the key genes involved in the subchondral bone pathological process of OA. Fifty gene expression profiles of GSE51588 were downloaded from the Gene Expression Omnibus database. The OA‐associated genes and gene ontologies were acquired from JuniorDoc. Weighted gene coexpression network analysis was used to find disease‐related networks based on 21756 gene expression correlation coefficients, hub‐genes with the highest connectivity in each module were selected, and the correlation between module eigengene and clinical traits was calculated. The genes in the traits‐related gene coexpression modules were subject to functional annotation and pathway enrichment analysis using ClusterProfiler. A total of 73 gene modules were identified, of which, 12 modules were found with high connectivity with clinical traits. Five modules were found with enriched OA‐associated genes. Moreover, 310 OA‐associated genes were found, and 34 of them were among hub‐genes in each module. Consequently, enrichment results indicated some key metabolic pathways, such as extracellular matrix (ECM)‐receptor interaction (hsa04512), focal adhesion (hsa04510), the phosphatidylinositol 3'‐kinase (PI3K)‐Akt signaling pathway (PI3K‐AKT) (hsa04151), transforming growth factor beta pathway, and Wnt pathway. We intended to identify some core genes, collagen (COL)6A3, COL6A1, ITGA11, BAMBI, and HCK, which could influence downstream signaling pathways once they were activated. In this study, we identified important genes within key coexpression modules, which associate with a pathological process of subchondral bone in OA. Functional analysis results could provide important information to understand the mechanism of OA.     

转基因植物中标记基因的消除

随着转基因植物的商业化,植物遗传转化技术将为农业生产带来一场新的革命,新的基因转化程序要求转基因为单拷贝,不带有标记基因,并在不同的转化体中表达一致,稳定遗传,本文讨论了转基因植物中有关标记基因及其安全性和标记基因消除的方法等问题。     

银杏叶提取物猴头菌转化前后降血糖作用的比较研究

以正常对照组、模型对照组和阳性(二甲双胍)对照组为参照,试验比较了银杏叶提取物(EGB)、猴头菌转化EGB的产物、猴头菌发酵液、猴头菌发酵液中添加EGB对链脲佐菌素诱导的2型糖尿病模型大鼠血糖和血脂代谢的调节作用以及对自由基清除作用。结果显示:相对于其他给药组,猴头菌转化EGB的转化产物能更加显著地降低糖尿病模型大鼠的血糖和果糖胺水平,但是对胰岛素水平无显著的调节作用,与模型对照组和其他给药组相比,EGB转化产物可以显著提高超氧化物岐化酶活性;与模型对照组相比亦可显著降低丙二醛水平,但与其他给药组相比其降丙二醛作用差异不明显。本项研究对采用微生物转化法提高植物提取物药用效果提供了参考资料。     

Ascertainment bias in rate ratio estimation from case-sibling control studies of variable age-at-onset diseases

Motivated by a Finnish case-control study of early onset diabetes in which diabetic children are matched to sibling controls, we investigate ascertainment bias of the usual rate ratio estimator from case-control data under simplex complete ascertainment of families during a fixed interval of time. Analytic results indicate that the assumptions necessary for valid estimation are that the disease is rare and the factors under study are exchangeable--essentially that the covariate distribution does not depend on calendar time or birth order. Further, we found that the rare disease assumption could be dropped by restricting to cases that were diagnosed during the enrollment period of the study or including all cases but eliminating the proband as a control for non-enrollment-period cases. An important consequence of this work is that standard family-based case-control studies are subject to ascertainment bias if exchangeability of the covariates under investigation does not hold.