Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation

Telomere shortening limits the proliferative lifespan of human cells by activation of DNA damage pathways, including upregulation of the cell cycle inhibitor p21 (encoded by Cdkn1a, also known as Cip1 and Waf1)) (refs. 1-5). Telomere shortening in response to mutation of the gene encoding telomerase is associated with impaired organ maintenance and shortened lifespan in humans and in mice. The in vivo function of p21 in the context of telomere dysfunction is unknown. Here we show that deletion of p21 prolongs the lifespan of telomerase-deficient mice with dysfunctional telomeres. p21 deletion improved hematolymphopoiesis and the maintenance of intestinal epithelia without rescuing telomere function. Moreover, deletion of p21 rescued proliferation of intestinal progenitor cells and improved the repopulation capacity and self-renewal of hematopoietic stem cells from mice with dysfunctional telomeres. In these mice, apoptotic responses remained intact, and p21 deletion did not accelerate chromosomal instability or cancer formation. This study provides experimental evidence that telomere dysfunction induces p21-dependent checkpoints in vivo that can limit longevity at the organismal level.     

大学生创业教育新模型

大学生学生创业对于解决大学生就业难问题以及促进大学生群体进行科技创新和促进国家经济发展等方面都有积极的作用。然而相对于美国、日本等国家的大学生选择自主创业的高比率,我国大学生选择自主创业的数量却并不多。由麦可思研究院调查编著的《2014中国大学生就业报告》指出在2013届约727万人的大学毕业生中自主创业比例仅为2.3%,仅为2013年769770万就业人员的0.21‰。国内大学生自主创业不积极的深层原因是国内大学创业教育的不完善。针对此问题,该文将通过结合对国外大学生创业教育和国内创业教育现状进行研究,对上海大学生的创业心态进行问卷调查,总结并建立了相关的创业教育模型。     

超薄高分子材料热管(英文)

热管具有远高于大多数金属的导热性能,已被广泛应用于电子元器件的散热方面.由于电子元器件正朝着微型化、薄型化、片式化和高功率等趋势发展,因此散热元件必须同时具备轻薄和高导热系数的特点.本文介绍了一种由高分子材料制造的超薄热管的设计和制造过程.其厚度为0.30 mm,大小为2 cm×6 cm,输入功率为9.54 W时,有效传热系数为541 W/(m K).管壳材料为kapton薄膜,吸液芯和蒸汽腔均由光阻SU8组成,光阻SU8柱子的大小和柱子之间的间隔差异为吸液芯提供了毛细血力;另外,通过原子层积电镀,SU8光阻和kapton薄膜都覆盖上一层极薄的Ti O2膜,改善了表面和吸液芯的亲水性能,同时实现了密封.     

Elevational patterns and determinants of plant diversity in the Baekdudaegan Mountains, South Korea: Species vs. functional diversity

The elevational gradient present in mountainous areas provides the most powerful natural experimental system available to clarify the ecological and evolutionary responses of living organisms to geophysical influences. In this study, we explored the elevational patterns of plant species and functional diversity and the effects of area, mid-domain effect, climatic variables and net primary productivity on the observed diversity patterns along the ridge of the Baekdudaegan Mountains, South Korea. Rapoport’s elevational rule was also evaluated by examining the relationship between elevational range size of plant species and elevation. A total of 802 plant species from 97 families and 342 genera were found in 1100 plots along a 200–-1900-m elevational gradient along the ridge. The elevational patterns of plant species diversity along the ridge of the Baekdudaegan depicted distinctly hump-shaped patterns, whereas the functional diversity decreased monotonically with elevation. The mid-domain effect was the most powerful explanatory variable for species diversity patterns. However, climatic variables were better predictors for functional diversity. Moreover, Rapoport’s elevational rule was not supported. Our study suggests that different elevational patterns may be observed among different diversity measurements even in the same taxon and that there may be fundamental differences in the mechanisms underlying these diversity patterns.     

Jelly belly protein activates the receptor tyrosine kinase Alk to specify visceral muscle pioneers

The secreted protein Jelly belly (Jeb) is required for an essential signalling event in Drosophila muscle development. In the absence of functional Jeb, visceral muscle precursors are normally specified but fail to migrate and differentiate. The structure and distribution of Jeb protein implies that Jeb functions as a signal to organize the development of visceral muscles. Here we show that the Jeb receptor is the Drosophila homologue of anaplastic lymphoma kinase (Alk), a receptor tyrosine kinase of the insulin receptor superfamily. Human ALK was originally identified as a proto-oncogene, but its normal function in mammals is not known. In Drosophila, localized Jeb activates Alk and the downstream Ras/mitogen-activated protein kinase cascade to specify a select group of visceral muscle precursors as muscle-patterning pioneers. Jeb/Alk signalling induces the myoblast fusion gene dumbfounded (duf; also known as kirre) as well as org-1, a Drosophila homologue of mammalian TBX1, in these cells.     

TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA

Maintenance of telomeres requires both DNA replication and telomere 'capping' by shelterin. These two processes use two single-stranded DNA (ssDNA)-binding proteins, replication protein A (RPA) and protection of telomeres 1 (POT1). Although RPA and POT1 each have a critical role at telomeres, how they function in concert is not clear. POT1 ablation leads to activation of the ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase at telomeres, suggesting that POT1 antagonizes RPA binding to telomeric ssDNA. Unexpectedly, we found that purified POT1 and its functional partner TPP1 are unable to prevent RPA binding to telomeric ssDNA efficiently. In cell extracts, we identified a novel activity that specifically displaces RPA, but not POT1, from telomeric ssDNA. Using purified protein, here we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) recapitulates the RPA displacing activity. The RPA displacing activity is inhibited by the telomeric repeat-containing RNA (TERRA) in early S phase, but is then unleashed in late S phase when TERRA levels decline at telomeres. Interestingly, TERRA also promotes POT1 binding to telomeric ssDNA by removing hnRNPA1, suggesting that the re-accumulation of TERRA after S phase helps to complete the RPA-to-POT1 switch on telomeric ssDNA. Together, our data suggest that hnRNPA1, TERRA and POT1 act in concert to displace RPA from telomeric ssDNA after DNA replication, and promote telomere capping to preserve genomic integrity.     

The HIC signalling pathway links CO2 perception to stomatal development

Stomatal pores on the leaf surface control both the uptake of CO2 for photosynthesis and the loss of water during transpiration. Since the industrial revolution, decreases in stomatal numbers in parallel with increases in atmospheric CO2 concentration have provided evidence of plant responses to changes in CO2 levels caused by human activity. This inverse correlation between stomatal density and CO2 concentration also holds for fossil material from the past 400 million years and has provided clues to the causes of global extinction events. Here we report the identification of the Arabidopsis gene HIC (for high carbon dioxide), which encodes a negative regulator of stomatal development that responds to CO2 concentration. This gene encodes a putative 3-keto acyl coenzyme A synthase--an enzyme involved in the synthesis of very-long-chain fatty acids. Mutant hic plants exhibit up to a 42% increase in stomatal density in response to a doubling of CO2. Our results identify a gene involved in the signal transduction pathway responsible for controlling stomatal numbers at elevated CO2.     

Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells

The complete 1,210-amino acid sequence of the human epidermal growth factor (EGF) receptor precursor, deduced from cDNA clones derived from placental and A431 carcinoma cells, reveals close similarity between the entire predicted v-erb-B mRNA oncogene product and the receptor transmembrane and cytoplasmic domains. A single transmembrane region of 23 amino acids separates the extracellular EGF binding and cytoplasmic domains. The receptor gene is amplified and apparently rearranged in A431 cells, generating a truncated 2.8-kilobase mRNA which encodes only the extracellular EGF binding domain.     

PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells

Obesity and type-2 diabetes have increased markedly over the past few decades, in parallel. One of the major links between these two disorders is chronic, low-grade inflammation. Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and ultimately other tissues, leading to metabolic abnormalities such as insulin resistance, type-2 diabetes and fatty-liver disease. Although invasion of VAT by pro-inflammatory macrophages is considered to be a key event driving adipose-tissue inflammation and insulin resistance, little is known about the roles of other immune system cell types in these processes. A unique population of VAT-resident regulatory T (Treg) cells was recently implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity. Here we identify peroxisome proliferator-activated receptor (PPAR)-γ, the 'master regulator' of adipocyte differentiation, as a crucial molecular orchestrator of VAT Treg cell accumulation, phenotype and function. Unexpectedly, PPAR-γ expression by VAT Treg cells was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone. These findings suggest a previously unknown cellular mechanism for this important class of thiazolidinedione drugs, and provide proof-of-principle that discrete populations of Treg cells with unique functions can be precisely targeted to therapeutic ends.