A Novel Mouse Model Reveals that Polycystin-1 Deficiency in Ependyma and Choroid Plexus Results in Dysfunctional Cilia and Hydrocephalus

Polycystin-1 (PC-1), the product of the PKD1 gene, mutated in the majority of cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD), is a very large (∼520 kDa) plasma membrane receptor localized in several subcellular compartments including cell-cell/matrix junctions as well as cilia. While heterologous over-expression systems have allowed identification of several of the potential biological roles of this receptor, its precise function remains largely elusive. Studying PC-1 in vivo has been a challenging task due to its complexity and low expression levels. To overcome these limitations and facilitate the study of endogenous PC-1, we have inserted HA- or Myc-tag sequences into the Pkd1 locus by homologous recombination. Here, we show that our approach was successful in generating a fully functional and easily detectable endogenous PC-1. Characterization of PC-1 distribution in vivo showed that it is expressed ubiquitously and is developmentally-regulated in most tissues. Furthermore, our novel tool allowed us to investigate the role of PC-1 in brain, where the protein is abundantly expressed. Subcellular localization of PC-1 revealed strong and specific staining in ciliated ependymal and choroid plexus cells. Consistent with this distribution, we observed hydrocephalus formation both in the ubiquitous knock-out embryos and in newborn mice with conditional inactivation of the Pkd1 gene in the brain. Both choroid plexus and ependymal cilia were morphologically normal in these mice, suggesting a role for PC-1 in ciliary function or signalling in this compartment, rather than in ciliogenesis. We propose that the role of PC-1 in the brain cilia might be to prevent hydrocephalus, a previously unrecognized role for this receptor and one that might have important implications for other genetic or sporadic diseases.     

Gradational Forest Change along the Climatically Dry Valley Slopes of Bhutan in the Midst of Humid Eastern Himalaya

Altitudinal forest and climate changes from warm, dry valley bottom (1250 m a.s.l.) to cool, humid ridge top (3550 m a.s.l.) along the typical dry valley slopes of the Bhutan Himalaya were studied. Annual mean temperature decreased upslope with a lapse rate of 0.62 °C·100 m⁻¹ from 18.2 °C at the valley bottom to 4.3 °C at the ridge top. On the contrary volumetric soil moisture content increased from 14.7 to 75.0%. This inverse relationship is the major determinant factor for the distribution of different forest types along the altitudinal gradient. Based on the quantitative vegetation data from 15 plots arranged ca. 200 m in altitude interval (1520–3370 m a.s.l.), a total of 83 tree species belonging to 35 families were recorded. Three major formation types of lower and upper coniferous forests, and a mid-altitude evergreen and deciduous broad-leaved forest were contrasted. Including two transitional types, five forest zones were categorized based on cluster analysis, and each zone can be characterized by the dominants and their phytogeographical traits, viz. (1) west Himalayan warm, dry pine (1520–1760 m a.s.l.), (2) wide ranging east-west Himalayan mixed broad-leaved (1860–2540 m a.s.l.), (3) humid east Himalayan evergreen broad-leaved (2640–2820 m a.s.l.), (4) cool, humid east Himalayan conifer (2950–3210 m a.s.l.), and (5) wide ranging cold, humid conifer (3305–3370 m a.s.l.). Structurally, total basal area (biomass) increased from 15.2 m² ha⁻¹ in the pine forest (1520 m) to 101.7 m² ha⁻¹, in the conifer forest (3370 m a.s.l.). Similarly, soil organic carbon increased from 2.7 to 11.3% and nitrogen from 0.2 to 1.9% indicating dry, poor nutrient fragile ecosystem at the dry valley bottom. We concluded that low soil moisture content (<20%) limits downslope extension of broad-leaved species below 1650 m a.s.l. while coldest month’s mean temperature of −1 °C restricted the upslope extension of evergreen broad-leaved species above 3000 m a.s.l. Along the dry valley slopes, the transition from dry pine forest in the valley bottom, to a mixture of dry west Himalayan evergreen and deciduous east Himalayan broad-leaved, and to humid evergreen oak–laurel forests feature a unique pattern of forest type distribution.     

甘孜藏族自治州生态系统生产总值核算研究

甘孜藏族自治州(以下简称甘孜州)生态状况良好而经济相对滞后,评估甘孜州生态系统服务功能及其价值,对甘孜州社会经济的可持续发展具有一定的促进作用。通过核算甘孜州的生态系统生产总值(GEP),包括对甘孜州的产品提供服务、调节服务和文化服务进行价值评估,以期用直观的经济数据揭示甘孜州生态系统对人们的直接贡献。核算结果显示,甘孜州2010年全州生态系统生产总值(GEP)为7545.59亿元,人均71.18万元,是当年该州国内生产总值(GDP)和人均GDP的约61倍。其中,调节服务的价值最大,为6842.28亿元,占GEP总值的90.68%;产品提供服务和文化服务的价值分别为632.64亿元和70.67亿元,占GEP的8.38%和0.94%。研究认为甘孜州生态系统服务功能价值巨大,保护甘孜州生态系统就是保护人们的福祉,该结果可以为甘孜州的生态系统管理、生态保护和生态补偿提供重要依据。     

Nephrocystin-1 Forms a Complex with Polycystin-1 via a Polyproline Motif/SH3 Domain Interaction and Regulates the Apoptotic Response in Mammals

Mutations in PKD1, the gene encoding for the receptor Polycystin-1 (PC-1), cause autosomal dominant polycystic kidney disease (ADPKD). The cytoplasmic C-terminus of PC-1 contains a coiled-coil domain that mediates an interaction with the PKD2 gene product, Polycystin-2 (PC-2). Here we identify a novel domain in the PC-1 C-terminal tail, a polyproline motif mediating an interaction with Src homology domain 3 (SH3). A screen for interactions using the PC-1 C-terminal tail identified the SH3 domain of nephrocystin-1 (NPHP1) as a potential binding partner of PC-1. NPHP1 is the product of a gene that is mutated in a different form of renal cystic disease, nephronophthisis (NPHP). We show that in vitro pull-down assays and NMR structural studies confirmed the interaction between the PC-1 polyproline motif and the NPHP1 SH3 domain. Furthermore, the two full-length proteins interact through these domains; using a recently generated model system allowing us to track endogenous PC-1, we confirm the interaction between the endogenous proteins. Finally, we show that NPHP1 trafficking to cilia does not require PC-1 and that PC-1 may require NPHP1 to regulate resistance to apoptosis, but not to regulate cell cycle progression. In line with this, we find high levels of apoptosis in renal specimens of NPHP patients. Our data uncover a link between two different ciliopathies, ADPKD and NPHP, supporting the notion that common pathogenetic defects, possibly involving de-regulated apoptosis, underlie renal cyst formation.     

基于生态系统生产总值核算的习水县生态保护成效评估

本文以国家级重点生态功能区—贵州省习水县为例,探讨以生态系统生产总值(Gross Ecosystem Product, GEP)为手段评估重点生态功能区生态保护成效的应用方法。通过核算习水县2000年和2010年的GEP,分析各生态系统服务价值及其变化特征来获取其生态保护成效。研究结果显示:2010年习水县GEP为223.35亿元,是当年该县国内生产总值(Gross Domestic Product, GDP)的约4倍;2000—2010年,习水县GEP共增加37.87亿元,增幅为20.42%。总体上习水县生态保护成效较为显著。主要表现为在10年间其提供的生态产品以及调节、文化服务的总价值均呈现增长,且林地、草地等重要土地利用类型的面积逐步增加。此外,本文还进一步探究了土地利用变化对生态系统服务价值的影响,以便揭示生态系统服务价值变化的根源,从而可以有效保护生态环境,实现区域经济发展与生态建设相协调。     

Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis

1. Download high-res image (120KB)
2. Download full-size image

     

Potential of resveratrol in the treatment of heart failure

The concept of food has expanded beyond its traditional role of survival and hunger satisfaction, to include a role in the prevention and treatment of disease. Polyphenols are classes of compounds that are synthesized by plants to serve a wide variety of functions including growth pollination and defense. These compounds have recently received increased attention in medical research. In this group, one of the most studied has been resveratrol (3,5,4,-trihydroxystilbene), a polyphenol, which is found predominantly in grapes and berries. Over the past two decades, researchers have studied the ability of resveratrol to prevent or reverse the development of abnormalities in heart structure and function in animal models of heart disease and heart failure. The results from animal studies have been promising, and very recently, this knowledge has been translated into examining the efficacy of resveratrol in humans with heart disease/failure. In this review we will discuss the current status of resveratrol research on cardioprotection.