Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint

During electron transport, the mitochondrion generates ATP and reactive oxygen species (ROS), a group of partially reduced and highly reactive metabolites of oxygen. In this in vivo genetic analysis in Drosophila melanogaster, we establish that disruption of complex I of the mitochondrial electron transport chain specifically retards the cell cycle during the G1-S transition. The mechanism involves a specific signaling cascade initiated by ROS and transduced by ASK-1, JNK, FOXO and the Drosophila p27 homolog, Dacapo. On the basis of our data combined with previous analyses of the system, we conclude that mitochondrial dysfunction activates at least two retrograde signals to specifically enforce a G1-S cell cycle checkpoint. One such signal involves an increase in AMP production and downregulation of cyclin E protein; another independent pathway involves increased ROS and upregulation of Dacapo. Thus, our results indicate that the mitochondrion can use AMP and ROS at sublethal concentrations as independent signaling molecules to modulate cell cycle progression.     

The utility F-box for protein destruction

A signature feature of all living organisms is their utilization of proteins to construct molecular machineries that undertake the complex network of cellular activities. The abundance of a protein element is temporally and spatially regulated in two opposing aspects: de novo synthesis to manufacture the required amount of the protein, and destruction of the protein when it is in excess or no longer needed. One major route of protein destruction is coordinated by a set of conserved molecules, the F-box proteins, which promote ubiquitination in the ubiquitin-proteasome pathway. Here we discuss the functions of F-box proteins in several cellular scenarios including cell cycle progression, synapse formation, plant hormone responses, and the circadian clock. We particularly emphasize the mechanisms whereby F-box proteins recruit specific substrates and regulate their abundance in the context of SCF E3 ligases. For some exceptions, we also review how F-box proteins function through non-SCF mechanisms.     

A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration

Epithelial organs, including the lung, are known to possess regenerative abilities through activation of endogenous stem cell populations, but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung, its absence in Gata6-null lung epithelium leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation. This expansion of BASCs was the result of a pronounced increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the noncanonical Wnt receptor Fzd2 was downregulated in Gata6 mutants and increased Fzd2 or decreased beta-catenin expression rescued, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, canonical Wnt signaling was activated in the niche containing BASCs and forced activation of Wnt signaling led to a large increase in BASC numbers. Moreover, Gata6 was required for proper lung epithelial regeneration, and postnatal loss of Gata6 led to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration.     

Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer

Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.     

多酸衍生物非线性光学性质的理论研究新进展

近年来,分子基非线性光学材料因其优异的非线性光学特性受到了人们集中的关注,多金属氧酸盐具有多样的结构和良好的电子性质,作为优良的无机构筑模块参与到分子设计中,可以获得有较好应用前景的非线性光学材料.本文在微结构非线性光学材料方面综合概述了Keggin型和Lindqvist型多酸衍生物类非线性光学材料的理论研究及分子设计进展.     

Life histories of stoneflies (Plecoptera) in the Rio Conejos of southern Colorado

Thirty-one stonefly species representing eight families were collected during the March 1987 to May 1990 study period. Genera represented by more than one species included Capnia, Utacapnia, Taenionema, Suwallia, Triznaka, Isogenoides, and Isoperla . Peak species richness was recorded on or near the summer solstice in 1988 and 1989. Climatic differences between years were reflected in nymphal development and emergence phenology of most species. New or important corroborative life history data are presented for 11 stonefly species of this assemblage. The hyporheic nymphal development of most cholroperlid species limited the number of early instars sampled and our capacity to interpret voltinism. Limited nymphal data suggested a univoltine-slow cycle for Plumiperla diversa (Frison). Adults of Suwallia pallidula (Banks) and S. wardi (Banks) were present for an extended summer period, but the bulk of their respective emergence times was temporally separated. Isogenoides zionensis Hanson, Pteronarcella badia (Hagen), and Pteronarcys californica Newport were all shown for the first time to have a 9-10 mo egg diapauses, and all three species have a semivoltine life cycle. Skwala Americana (Klápalek) and Isoperla fulva Claassen were further confirmed to have univoltine-slow cycles. Univoltine-fast and univoltine-slow life cycles are reported for the first time in I. phalerata and I. quinquepunctata , respectively. Regression analysis revealed that six of the eight abunduant species had extended emergence patterns (slopes of < 5%/d), while only two had synchronous patterns. Warmer spring and summer temperatures in 1989 increased the slopes for five of the eight species studied, but did not change their synchrony designation. Nine of 11 abundant species advanced their median emergence date in 1989 over 1988. This and the higher slope values are consistent with a hurried nymphal development and narrower emergence period due to the warmer thermal regime of 1989.     

几种植物分生组织细胞高尔基体的超微结构

应用电镜观察石刁柏胚芽、水仙幼叶、根尖和甜菊愈伤组织等分生细胞高尔基体、液泡以及内质网和细胞壁之间的联系,在高尔基体的形成面,由内质网芽生的运输小泡,分布于高尔基潴泡周围,高尔基潴泡末端扩大发展形成高尔基液泡,在分生细胞的大小液泡,是由高尔基潴泡末端扩大形成的,这些液泡合并形成中央液泡.在细胞壁的形成过程中,高尔基小泡沿着细胞壁边缘转移,并且与质膜融合。     

铁铬铝合金晶粒长大及合金中稀土元素

研究了不同稀土含量铁铬铝合金,在高温下晶粒长大及界面结构。结果表明:在1200℃以上高温,稀土组元(以La为主)对抑制合金的晶界长大有一定效果,La_2O_3可作为TiN相析出的形核中心,细小TiN质点可在晶界上出现,阻碍晶界迁移;在变温过程中,La向界而扩散,在晶界以La_2O_3形式出现,同时稀土加速氧穿过氧化膜向基体中渗透,导致Al_2O_3及La_2O_3在基体中形成。     

机械设计中的模糊规划模型及其解法

本文应用 Fuzzy 集理论,描述了机械设计中的模糊现象。提出了机械设计的 Fuzzy 最优化方法。并进一步论证了 Fuzzy 最优化可转化为普通规划问题。通过实例计算,证明了本文提出的方法是有效的。     

Petrological implication of wagnerite-Ma5bc in the quartzofeldspathic gneiss, Larsemann Hills, East Antarctica

Mg dominantmineralsofwagnerite triplite group,i.e.(Mg,Fe,Mn)2(PO4)(F,OH),arerelativelyrare,buthavebeenfoundinawidevariety ofgeologicenvironments,includingmetamorphic rocksofallgrades[1]suchasquartz carbonateveinsof hydrothermalorigin,pegmatites,kyanite quartzite,micaschist,sillimanitegneiss,andmagnetiteores.Uptonow,wagneriteispresentmainlyasthe Ma2bcpolytype,anaccessorymineralincalcium poorrocks[2,5]inwhichapatite,ifpresent,oftenoc cursasretrograderimaroundwagnerite.Henriques[6]reportedasma…