An isogenetic myoblast expression screen identifies DUX4-mediated FSHD-associated molecular pathologies

Facioscapulohumeral muscular dystrophy (FSHD) is caused by an unusual deletion with neomorphic activity. This deletion derepresses genes in cis; however which candidate gene causes the FSHD phenotype, and through what mechanism, is unknown. We describe a novel genetic tool, inducible cassette exchange, enabling rapid generation of isogenetically modified cells with conditional and variable transgene expression. We compare the effects of expressing variable levels of each FSHD candidate gene on myoblasts. This screen identified only one gene with overt toxicity: DUX4 (double homeobox, chromosome 4), a protein with two homeodomains, each similar in sequence to Pax3 and Pax7. DUX4 expression recapitulates key features of the FSHD molecular phenotype, including repression of MyoD and its target genes, diminished myogenic differentiation, repression of glutathione redox pathway components, and sensitivity to oxidative stress. We further demonstrate competition between DUX4 and Pax3/Pax7: when either Pax3 or Pax7 is expressed at high levels, DUX4 is no longer toxic. We propose a hypothesis for FSHD in which DUX4 expression interferes with Pax7 in satellite cells, and inappropriately regulates Pax targets, including myogenic regulatory factors, during regeneration.     

Aldosterone induces myofibroblastic transdifferentiation and collagen gene expression through the Rho-kinase dependent signaling pathway in rat mesangial cells

There is accumulating evidence indicating the role of aldosterone in the pathogenesis of hypertension and renal injury. In this study, we investigated the role of the Rho-kinase dependent signaling pathway in aldosterone-induced myofibroblastic transdifferentiation and collagen gene expression in rat mesangial cells (RMCs). Stimulation with aldosterone (1 nmol/L) significantly increased phosphorylation of myosin phosphatase target subunit-1 (MYPT-1), a marker of Rho-kinase activity, with a peak at 20 min in RMCs. Pre-incubation with a selective mineralocorticoid receptor antagonist, eplerenone (10 µmol/L), or a specific Rho-kinase inhibitor, Y27632 (10 µmol/L), attenuated the aldosterone-induced increase in MYPT-1 phosphorylation. Aldosterone also induced hypertrophy in RMCs, accompanied by an increase in actin polymerization and expression of α-smooth muscle actin (α-SMA), a myofibroblastic transdifferentiation marker. Collagen type I, III and IV mRNA levels were also increased with aldosterone stimulation. Pre-treatment with eplerenone or Y27632 prevented the aldosterone-induced cell hypertrophy, actin polymerization, the increase in α-SMA expression and the increases of collagen type I, III, IV mRNA levels in RMCs. These results suggest that aldosterone-induced mesangial cell hypertrophy is associated with cell transformation, leading to an increase in collagen gene expression via the Rho-kinase dependent signaling pathway.     

Pollen Morphology of Eight Genera of the Subtribe Mutisiinae Less. sensu Bremer （Compositae） from Asia

The pollen morphology of 28 species and one variety representing eight genera of the subtribe Mutisiinae Less. sensu Bremer （Compositae） was investigated by scanning electron microscopy （SEM） and light microscopy. The pollen grains are usually radically symmetrical, isopolar, and tricolporate. The shape varies from spheroidal to subprolate in equatorial view and is three-lobed circular in polar view. Based on exine sculpturing observed under SEM, the pollen grains can be divided into three types： （i） type Ⅰ, with macrogranulate sculpture; （ii） type Ⅱ, with a finely granulate sculpture; and （iii） type Ⅲ with spiny sculpture. The palynological data showed that the Macroclinidium Maxim. was remarkably distinguished from those of the other seven genera. The variation of pollen characteristics within the Mutisiinae in Asia is little at species level, but it proves some useful information for studying the relationships among genera and it has an important significance in further understanding the evolutionary history of Mutisiinae.     

Ectopic Expression of the Pttknl Gene Induces Alterations in the Morphology of the Leaves and Flowers in Petunia hybrida Vilm.

A novel knottedl-like homeobox （knox） gene, Pttknl （Populus tremulaxtremuloides knottedl）, isolated from the cambial region of hybrid aspen, was introduced into Petunia hybrida Vilm. using the leafdisc method mediated by Agrobacterium. A series of novel phenotypes was observed in transgenic petunia plants, including the formation of ectopic spikes on the adaxial surface of corollas and small petals on the abaxial surface of corollas, fusion of floral organs, shortening of corolla midribs, the formation of tumor-like knots along the midrib on the abaxial surface and serrated lobs of corolla margins, and alterations in petal color; except for changes in the leaves and plant architecture, RT-PCR showed that the Pttknl gene was expressed in the leaves of different petunia transgenic plants, whereas no signal was detected in wild-type plants. The possible function of Pttknl in leaf and flower development is discussed.     

Mapping of a Wheat Resistance Gene to Yellow Mosaic Disease by Amplified Fragment Length Polymorphism and Simple Sequence Repeat Markers

Wheat （Triticum aestivum L.） yellow mosaic virus （WYMV） is transmitted by a fungal vector through soil and causes serious wheat yield losses due to yellow mosaic disease, with yellow-streaked leaves and stunted plants. In the present study, the amplified fragment length polymorphisms （AFLP） and simple sequence repeat （SSR） were used to identify the molecular linkages with the resistance gene against WYMV. Bulked segregant analysis was performed with an F2 population derived from the cross of cultivar Ningmai 9 （resistant） × cultivar Yangmai 10 （susceptible）. By screening among the resistant or susceptible parents, the F2 pools and the individuals in the F2 population with 64 combined selective AFLP primers （EcoRI/MseI） or 290 reported SSR primers, a polymorphic DNA segment （approximately 120 bp） was amplified using the primer pair E2/M5, and an SSR marker （approximately 180 bp） was located on wheat chromosome 2A using the primer Xgwm328. Analysis with MAPMAKER/Exp Version 3.0b （Whitehead institute for Biomedical Research, Cambridge, MA, USA） indicated that these two markers were dominantly associated with the resistance gene at distances of 5.4 cM or 17.6 cM, respectively. The resistance gene to WYMV derived from Ningmai 9, is temporarily named YmNM, and was mapped to wheat chromosome 2A.     

Overexpression of a novel gene , Cms1, can rescue the growth arrest of a Saccharomyces cerevisiae mcm10 suppressor

INTRODUCTIONDNA replication is a fundamenial process thatmust occur only once at each ce1l cycle. This restrictcontrol appears to be achieved through the coordi-nated actiVities of numerous proteins. The buddingyeast Saccharompes cerevhaae provides an excellenteukaryotic model fOr study of proteins invo1ved inthe control of DNA replication.In the budding yeast, minichromosome mainte-nance (MCM) proteins, MCM2-7, are a family of strsequence-related proteins that play crucia1 roles inr…     

YR-黏和染色体模型初探(下)

我们创建了一个新的染色体模型:YR-黏和染色体模型,30nm螺线管通过JW-梯(或YR-梯)、染色线经螺旋化形成染色体[1].通过包装比、长度的推算、染色体结构的推算、以及碱基对的推算都与实验观测值吻合,确认了YR-黏和模型的可信度.YR-染色体模型能自然、合理地解释所有遗传现象,如交换、着丝粒、全身着丝粒或弥散型着丝粒染色体、同源染色体联会及联会复合体的中央区、多线染色体与膨突、灯刷染色体、染色体分带、姊妹染色体由前期到中期不分开、花粉管会导入外源遗传物质、高等生命是怎样从原始生物进化而来的等等。 Abstract:We provide a chromosome model YR-cohesion chromosome model.30nm solenoid fold and bent through JW-ladder and chromonema spiraling to chromosomeIll.It is checked by this calculation of picked ration,length,chromosomal structure and DNA base pairs,which are all consonant with practical resultsIll.YR-cohesion chromosome model will give a better answer to the questions such as exchange,centromere,holocentromere,synaptonemal complex,polytene chromosome,puff,lampbrush chromosome,chromosome banding,non-segregation of sister chromatid,pollentube pathway and biological evolution.     

对郭德栋主编的中若干问题的商榷

本文参阅有关文献及十多年遗传学教学中所使用的不同版本的教材,对郭德栋主编的<遗传学>教材中的若干问题进行了商榷。 Abstract:Consulted some reference books and textbooks of different versions used over ten years,we are about to discuss some problems in the textbook “Genetics” edited by Guo De-dong in this paper.     

空间诱变水稻大粒型突变体的遗传育种研究

对粳稻农垦58经空间诱变产生的大粒型突变体进行大粒型性状的遗传分析和育种应用研究。结果表明,大粒型突变体的籽粒大小（以籽粒体积表示）表现为受多基因控制的数量性状。大粒型突变体谷粒细长,具馨香味,外观品质优,对粳稻的亲和性好,是一个罕见的优质米资源。以大粒型突变体为供体,高产、外观米质差的晚粳推广品种为受体,采用不饱和回交结合分离世代糙米外观品质鉴定的方法,将大粒型突变体的优质性状导入晚粳背景,选育出外观米质优的晚粳新品系。对采用不饱和回交方法改良数量性状进行了讨论。 Abstract:The inheritance and utilization of a stable large-grain mutant,selected from the induced generation derived from japonica Nongkeng 58 after space treatment carried by recoverable satellite,were analyzed.The results indicated that the grain volume of the large-grain mutant was quantitative trait controlled by multiple genes.The large-grain mutant had characteristics of slender grain,favorable scent,high apparent grain quality and good compatibility with japonica,and can be used as a valuable resource for improving grain quality.When high yield japonica variety with bad looking quality was used as a recurrent parent to cross with the mutant and a procedure of a limited backcross combined with identification of brown rice quality in segregation generations was applied,some japonica lines with good looking quality were developed.The utility of the limited backcross method for improvement of quantitative traits was discussed.