Interaction with polyglutamine-expanded huntingtin alters cellular distribution and RNA processing of huntingtin yeast two-hybrid protein A (HYPA)

Huntington disease (HD) is an autosomal inherited disorder that causes the deterioration of brain cells. The polyglutamine (polyQ) expansion of huntingtin (Htt) is implicated in the pathogenesis of HD via interaction with an RNA splicing factor, Htt yeast two-hybrid protein A/forming-binding protein 11 (HYPA/FBP11). Besides the pathogenic polyQ expansion, Htt also contains a proline-rich region (PRR) located exactly in the C terminus to the polyQ tract. However, how the polyQ expansion influences the PRR-mediated protein interaction and how this abnormal interaction leads to the biological consequence remain elusive. Our NMR structural analysis indicates that the PRR motif of Htt cooperatively interacts with the tandem WW domains of HYPA through domain chaperoning effect of WW1 on WW2. The polyQ-expanded Htt sequesters HYPA to the cytosolic location and then significantly reduces the efficiency of pre-mRNA splicing. We propose that the toxic gain-of-function of the polyQ-expanded Htt that causes dysfunction of cellular RNA processing contributes to the pathogenesis of HD.     

miR-34a expands myeloid-derived suppressor cells via apoptosis inhibition

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population and show significant expansion under pathological conditions. microRNA plays important roles in many biological processes, whether microRNAs have a function in the expansion of MDSCs is still not very clear. In this study, miR-34a overexpression can induce the expansion of MDSCs in bone marrow chimera and transgenic mice model. The experimental results suggest that miR-34a inhibited the apoptosis of MDSCs but did not affect the proliferation of MDSCs. The distinct mRNA microarray profiles of MDSCs of wild type and miR-34a over-expressing MDSCs combined with the target prediction of miR-34a suggest that miR-34a may target genes such as p2rx7, Tia1, and plekhf1 to inhibit the apoptosis of MDSCs. Taken together, miR-34a contributes to the expansion of MDSCs by inhibiting the apoptosis of MDSCs.     

BmCREC Is an Endoplasmic Reticulum (ER) Resident Protein and Required for ER/Golgi Morphology

Silkworm posterior silkgland is a model for studying intracellular trafficking. Here, using this model, we identify several potential cargo proteins of BmKinesin-1 and focus on one candidate, BmCREC. BmCREC (also known as Bombyx mori DNA supercoiling factor, BmSCF) was previously proposed to supercoil DNA in the nucleus. However, we show here that BmCREC is localized in the ER lumen. Its C-terminal tetrapeptide HDEF is recognized by the KDEL receptor, and subsequently it is retrogradely transported by coat protein I (COPI) vesicles to the ER. Lacking the HDEF tetrapeptide of BmCREC or knocking down COPI subunits results in decreased ER retention and simultaneously increased secretion of BmCREC. Furthermore, we find that BmCREC knockdown markedly disrupts the morphology of the ER and Golgi apparatus and leads to a defect of posterior silkgland tube expansion. Together, our results clarify the ER retention mechanism of BmCREC and reveal that BmCREC is indispensable for maintaining ER/Golgi morphology.     

Microtubule-dependent formation of the stigmoid body as a cytoplasmic inclusion distinct from pathological aggresomes

The stigmoid body (STB) is a neurocytoplasmic inclusion containing huntingtin-associated protein 1 (HAP1), an interactor of huntingtin, and its formation is induced by transfection of HAP1-cDNA into cultured cells. Although STB is believed to play a protective role in polyglutamine diseases, including Huntington’s disease and spinal and bulbar muscular atrophy, by sequestering the causative proteins, huntingtin and androgen receptor, respectively, its physiological function and formation remain poorly understood. Therefore, STB is occasionally confused with another cytoplasmic inclusion observed in polyglutamine diseases, the aggresome. Here we examined the subcellular dynamics of STB and compared it immunohistochemically and cytochemically with the aggresome in the rat brain and COS-7 or HeLa cells transfected with HAP1 and/or polyglutamine disease-associated genes. In time-lapse image analysis of HAP1-transfected cells, the HAP1-induced STB is formed from multiple fusions of small HAP1 inclusions characterized by vigorous cytoplasmic movement. In HAP1-transfected cells treated with a microtubule-depolymerizing drug, although the formation of small HAP1 inclusions was not affected, their fusion was critically inhibited. Immunohistochemistry and cytochemistry revealed the absence of association between STB and aggresomal markers, such as ubiquitin/proteasome, intermediate filaments, and the centrosome. Taken together, we concluded that STB is formed by a two-step process comprising microtubule-independent formation of small HAP1 inclusions and microtubule-dependent fusion of these inclusions, and that STB is distinct from pathological aggresomes.     

Invasion dynamics of the glassy-winged sharpshooter <Emphasis Type="Italic">Homalodisca vitripennis</Emphasis> (Germar) (Hemiptera: Cicadellidae) in French Polynesia

The glassy-winged sharpshooter, Homalodisca vitripennis (Germar) [formerly Homalodisca coagulata (Say)] (Hemiptera: Cicadellidae), has recently emerged as a serious invasive pest. From its natural range in the southeast USA and northeast Mexico, it invaded successively California (late 1980s), French Polynesia (1999), Hawaii (2004), and recently Easter Island (2005) inadvertently through the transportation of infested plants. In French Polynesia, H. vitripennis has reached impressive densities becoming an important pest threatening agriculture, native biodiversity, as well as being a major social nuisance. Since 1999, H. vitripennis spread rapidly from Tahiti to neighboring islands, colonizing most of the archipelagos of French Polynesia. In this paper, we present the results of surveys of H. vitripennis populations from 15 islands of French Polynesia and use these data to investigate the invasion dynamics and colonization processes of this pest in a tropical climate. We found H. vitripennis present in 10 islands with two new records confirmed. Our analyses suggest that: (1) H. vitripennis abundance is strongly associated with urbanization, with highest pest densities found in the most developed coastal areas of infested islands, (2) H. vitripennis may exhibit an Allee effect during the early phase of an invasion, and (3) the invasion dynamics of H. vitripennis conform to a stratified dispersal model marked by rapid long-distance human-mediated movement.     

Confirmation of the sex difference in continuing subperiosteal apposition

A major sex difference in the rate of continuing bone expansion was confirmed for 5660 adult subjects of European ancestry. The five-decade gain in metacarpal midshaft area amounted to 8.4% in 3455 females and 2.8% in 2205 males. There was no systematic age effect on the length of the second metacarpal. Accordingly, both bone expansion and the marked sex difference in its magnitude may be attributed to sex-specific aspects of ageing much like the sex difference in endosteal surface loss.     

Changes in Reproductive Allocation after Expansion from the Glacial Refugium and Implications for the Distribution Range in the Qinghai Tibet Plateau Native Herb,Gymnaconitum gymnandrum (Ranunculaceae)

A fundamental goal of ecology and evolution is to explain patterns of species distribution and abundance. However, the way in which stable distribution ranges are shaped by natural selection is still poorly understood, especially whether patterns of resource allocation have contributed to the range size and the formation of range boundary received little attention. For annual herb, the maximum reproductive allocation is predicted to be 50%, and thus we predicted that reproductive allocation might contribute to the formation of range boundary since plant will enhance allocations to reproduction in stressful environments. In this study, we presented our data on resource allocation between population from the glacial refegium and those from the marginal populations in Gymnaconitum gymnandrum, an alpine biennial native to the Qinghai Tibet Plateau, aiming to find the contribution of resource allocation to the formation of range boundary. Our results showed that resource allocations to vegetative organs, including roots, plant height and stem leaf biomass, were significantly higher in the refugium population that in the two marginal populations, and allocations to reproductive organs, including flower number and flower biomass, were significantly lower in one marginal population (Haibei population) than in the other marginal population (Xinghai population) and the refugium population (Tongren population). However, reproductive allocation was significantly higher in the marginal populations than in the refugium population. In addition, in each of the three populations, we found a positive relationship between the plant size and flower biomass but a negative relationship between the plant size and reproductive allocation. Our results indicated a size dependent reproductive allocation in Ggymnandrum, but we did not find a size threshold for reproduction in each of the three populations of this plant, which might be attributed to the life history of this biennial herb. We also suggested that reproductive allocation was increased during the process of range expansion and may rise to the optimal reproductive allocation in the marginal populations, which suggested the important role of sexual reproduction for plants in more stressful environments and the formation of range boundary. However, these conclusions need to be further proved in other plant species.     

基于GlobeLand30的城市生态用地时空变化特征——以北京市为例

在城市高速增长而土地资源有限的背景下,北京市探索了城市总体规划统领的生态保护与建设有效途径,探究其生态用地时空变化特征,能够为生态用地与建设用地同步规划和协调布局提供参考。本文基于北京市2000年、2010年和2020年的GlobeLand30土地覆盖数据,分析了2000-2020年生态用地与建设用地、农用地的相互转化,揭示了各类用地变化强度在不同距离及方位的空间分布特征,应用景观格局指数刻画了空间形态变化;通过景观扩张/收缩指数LESI判定生态用地空间形态变化模式;通过高斯两步移动搜索法2SFCA计算建设用地与生态用地的可达性。结果表明：（1）生态用地面积占比一直为13%~15%,但不同距离和方位的空间分布发生显著变化,生态条件较好区域受城市增长负面影响较大,生态条件相对薄弱区域的生态建设在城市增长中加强。（2）生态用地的空间形态变化不大,但空间分布趋于分散;生态用地增加以新生模式和扩展模式为主,减少则从消亡模式为主转向分裂模式和收缩模式为主。（3）建设用地与生态用地的可达性整体偏低,2000-2010年新增建设用地可达性的低等级占比高于既有建设用地,可达性高值区零散分布在中心区域;2010-2020年新增建设用地可达性的较高等级占比高于既有建设用地,可达性较高区域的空间分布更加均匀。