哺乳动物精子体外诱导的研究进展

研究雄性哺乳动物生殖细胞的增殖、分化、成熟机制以及对以上过程造成影响的诸多因素,为雄性不育症的治疗提供理论依据和潜在的治疗方法,研究人员不断尝试将各种种子细胞诱导为精子。体外诱导精子的实验由于具有可进行连续观察、排除了受体动物的个体差异影响、便于设计单因素实验等优点,近年来取得了许多突破性进展,精原干细胞(spermatagonial stem cell,SSC)、胚胎干细胞(embryonic stem cell,ESC)、诱导性多能干细胞(induced pluripotent stem cell,iPS)、间充质干细胞(mesenchymal stem cell,MSC)等都在体外被成功诱导为精子。就目前的哺乳动物精子体外诱导进展做一综述。     

白血病细胞的定向诱导分化及PADI4在诱导分化中的作用

白血病是血液系统的常见病和多发病,定向诱导白血病细胞分化是治疗白血病的重要策略之一。肽酰基精氨酸脱亚胺酶(PAD/PADI)是催化精氨酸转化为瓜氨酸的关键酶,在白血病诱导分化过程中起关键作用。国内外学者在白血病诱导分化的机制及策略方面开展了众多研究。本文对诱导白血病细胞定向分化为粒细胞、树突状细胞及巨噬细胞的研究概况及PADI4在白血病细胞定向分化中的机制研究进展作一综述。     

胰岛移植：寻找新的β细胞来源

胰岛移植被认为是一型糖尿病最有前景的治疗之一。Edmonton移植方案的出现为长期脱离外源胰岛素治疗提供了可能。胰岛移植目前面临的主要问题之一是移植细胞来源的短缺。本文总结了近年来关于可能用于移植的胰岛细胞来源的研究结果。一型糖尿病是一种针对胰岛β细胞的自身免疫性疾病，使用异体来源的β细胞恰恰可以避免自身免疫反应对新移植细胞的损伤，为胰岛细胞来源提供了无限可能。     

大鼠骨髓源神经干细胞的分离培养及鉴定

目的:对Wistar大鼠骨髓源神经干细胞进行分离、培养和鉴定,观察其生长方式和分化特征。方法:运用无血清培养基对Wistar大鼠骨髓基质细胞进行培养,对分离获得的悬浮生长的神经球采用免疫组织化学法检测CD133和Nestin表达情况。用血清诱导其分化,分化7 d后,采用免疫荧光细胞化学染色方法检测分化后GFAP、Map2、β-tubulinⅢ、Galc的表达情况。结果:大鼠骨髓基质细胞在无血清培养基中,呈悬浮状态生长,形成细胞球,经免疫荧光检测,细胞球呈CD133和Nestin阳性。将细胞球转入含血清培养基后,转为贴壁生长,经免疫荧光检测大部分已分化细胞呈GFAP阳性,少部分细胞呈MAP-2、β-tubulinⅢ及Galc阳性。结论:采用含bFGF、EGF的无血清培养基可培养出呈球状聚集生长、具多向分化潜能的大鼠骨髓源神经干细胞。     

盐霉素抗肿瘤机制的相关研究进展

肿瘤干细胞(CSCs)是一群存在于肿瘤细胞中的亚群,具有自我更新和产生新的不同分化程度的肿瘤细胞。干细胞亚群的存在使得肿瘤可以逃避化疗药物、靶向治疗药物以及放射治疗等治疗手段的杀伤作用,也是肿瘤复发和转移的重要原因之一。盐霉素是由白色链霉菌发酵产生的属于聚醚类的一元羧酸,近年来研究发现盐霉素能高效杀死多种肿瘤干细胞,并对多种肿瘤有明显的抑制作用,是一种很有开发潜力的抗肿瘤药物。其作用机制可能与诱导肿瘤干细胞凋亡与抑制有关。     

利用piggyBac转座子制备牛成体多能干细胞诱导技术研究

通过逆转录病毒等媒介表达核转录因子Oct4、Sox2、Klf4、c-Myc可将体细胞重编程为诱导多能干细胞(induced pluripotent stem cells,iPSc)。时至今日,已经报道了小鼠、人、大鼠、猪、羊、马、牛的iPS细胞,但大动物iPS的多能性特别是嵌合体形成和生殖细胞传代还没有得到确认。与逆转录病毒等不同的是,piggyBac转座子转染效率高且无病毒源性、操作简单,可以在转座酶的存在下被安全切除。首次尝试了采用piggyBac转座子携带鼠源Oct4、Sox2、Klf4、c-Myc、Rarg和Lrh1 6个核转录因子诱导胎牛成纤维细胞,成功获得牛类iPS细胞,其形态与小鼠胚胎干细胞相似,克隆边界清晰、呈丘状、克隆内细胞致密、核大。RT-PCR与免疫组织化学染色分析均显示牛类iPS细胞表达多能性基因。该类细胞体外诱导分化可形成类胚体EB,且表达3个胚层的基因;体内诱导分化可形成畸胎瘤,苏木精、伊红染色显示瘤体有三胚层的分化。上述结果显示利用piggyBac转座子制备牛多潜能干细胞诱导技术可行,产生的牛类iPS细胞具有潜在多能性。     

脂肪干细胞的研究进展

脂肪干细胞是成体间充质干细胞的一种,具有多向分化的潜能、取材容易、来源广泛适宜自体移植等优点,是继骨髓间充质干细胞之后的又一再生医学种子细胞的来源,成为国内外研究的热点。本文综述了脂肪干细胞的生物学特性与临床应用前景。     

中医药基于缺氧诱导途径调节肾间质纤维化

缺氧是肾小管萎缩、肾间质纤维化的潜在危险因素。缺氧通过多种信号通路诱导肾间质纤维化的发生,包括缺氧诱导因子途径、转化生长因子β途径、核因子-κB途径、Notch途径、Toll样受体/髓性分化因子-88途径、血管紧张素II/细胞活性氧途径等。中医药可通过多靶点、多途径调节相关信号通路的表达,干预肾间质纤维化进程。但目前对于在缺氧诱导的肾间质纤维化过程中发挥主导作用的机制研究不足,且中医药抑制缺氧诱导相关信号通路治疗肾间质纤维化的研究多借助于动物实验,与人体的复杂病变存在差异。将基础实验应用于临床实践,需注意以下几个方面:注重肾小球疾病伴肾小管间质损害的动物实验;中药成分复杂,用药需兼顾其有效性和安全性;重视研究中药复方的作用机制。目前慢性肾脏病治疗所面临的挑战仍然是抗纤维化治疗,适应病因病机的差异进行个体化治疗、改进诊断方法以及中西医协同治疗是以后研究的主要方向。     

甲状旁腺素对骨髓间充质干细胞增殖、分化和旁分泌功能的影响

目的观察甲状旁腺素(PTH)对体外培养人骨髓间充质干细胞(hMSCs)增殖、分化、干性(stemness)和旁分泌功能的作用。方法采用标准培养基体外培养人骨髓间充质干细胞,并将其分为对照组和PTH干预组,用细胞计数测试和BrdU增殖检测细胞增殖变化。用碱性磷酸酶染色、油红染色、阿利新蓝染色检测细胞分化情况。用Real-time PCR检测hMSCs OCT-4、Nanog、SOX-2、CCND1、C-MYC等基因表达情况。用ELISA方法检测hMSCs培养上清液基质细胞衍生因子-1(SDF-1)、胰岛素样生长因子(IGF-1)、血管内皮生长因子(VEGF)、骨形态发生蛋白2(BMP2)和Angiopoietin1蛋白水平。结果使用10-8mol/L~10-9mol/L的PTH干预6 d可明显促进hMSCs增殖(P<0.05),PTH 10-8mol/L促进成骨、软骨分化,抑制脂肪分化。PTH 10-8mol/L可明显诱导CCND1和C-MYC基因表达(均P<0.01),抑制OCT-4表达(P<0.01),抑制Nanog和SOX-2等表达(均P<0.05)),升高培养液中SDF-1、IGF-1、VEGF、BMP2和血管生成素1(Angiopoietin 1)蛋白水平(均P<0.05)。结论 PTH能促进hMSCs增殖,调节其分化,但不能维持hMSCs的干性。调节hMSCs的旁分泌功能对局部微环境合成代谢、细胞迁移和血管发生产生影响。     

RUNX2对BMP9诱导的间充质干细胞C3H10T1/2成骨分化的影响

目的:研究和确认RUNX2在骨形态发生蛋白9(BMP9)诱导的间充质干细胞C3H10T1/2成骨分化中的作用。方法:通过Western blot、RT-PCR、荧光素酶活性分析检测BMP9对RUNX2表达的影响;分别在过表达RUNX2和RNA干扰抑制RUNX2表达的情况下,利用碱性磷酸酶(ALP)活性测定和染色、钙盐沉积实验,免疫细胞化学和裸鼠皮下异位成骨实验分析RUNX2对于BMP9诱导的间充质干细胞成骨分化的影响。结果:BMP9可以促进RUNX2的表达;RUNX2体外可促进BMP9诱导的C3H10T1/2的ALP活性和钙盐沉积,却抑制了OCN表达,RUNX2还可促进BMP9诱导的裸鼠皮下异位成骨;而在降低RUNX2表达后,BMP9诱导的C3H10T1/2细胞的ALP活性、钙盐沉积、OCN表达和裸鼠皮下异位成骨均受到抑制。结论:RUNX2可以促进BMP9诱导的间充质干细胞C3H10T1/2细胞成骨分化。     

Movement on Shifting Sands: Deinstitutionalisation and People with Intellectual Disability in Australia, 1974–2014

This article reviews four decades of deinstitutionalisation policies in three Australian states, New South Wales, Victoria and Queensland. It seeks to understand the factors influencing the slow and haphazard progression of the movement and its more contested outcomes such as the redevelopment of some institutions and their replacement with other congregate or cluster housing models that are at odds with the original visions of community care and normalisation. The article highlights the consistent and effective opposition to deinstitutionalisation from some families of institution residents, and the shifting policy frameworks and ideologies—from ‘normalisation’ to ‘choice’—in which it progressed. In particular, the article highlights the intersections between deinstitutionalisation and urban policy. The article is based on a review of existing scholarly literature, policy documents, inquiry reports and media sources.     

再生混凝土抗碳化性能试验研究

主要研究混凝土水胶比、水泥用量、再生粗骨料来源、掺合料、再生粗骨料取代率对碳化速率的影响规律。试验表明,再生粗骨料取代率在50%左右、水胶比在0.3左右时的再生混凝土密实程度达到最佳状态,混凝土的抗碳化性能相对最好。     

浅谈中央空调系统冷热源方案的选择

中央空调系统冷热源的设计方案极大地影响着空调系统的初投资和运行费用,同时由于国内各地区的能源结构、政策导向、环保要求的不同都会影响方案选择的经济合理性。对冷热源选择需考虑的因素进行了叙述,比较了常用的冷热源组合方案及优缺点。以北京某办公楼中央空调系统为例,对不同的冷热源组合方案了经济分析和方案选择。     

Energy alternatives: the Indian perspective

India's immense geography provides her with a variety of ambient energy resources. This paper examines the non-conventional energy sources and their possible future in India. While the non-conventional energy sources include geothermal energy, waves, tides and ocean thermal energy in addition to direct solar radiation, the emphasis in the paper is on solar, biomass and wind energy applications. Conventional energy sources including coal, oil, gas and nuclear energy are not going to be adequate and the alternative sources discussed are not going to be capable of fully replacing the above sources in any foreseeable future. While these alternative sources are likely to be only a partial substitute and not a total replacement, their contribution can usually be well above 50 per cent of the total energy needs. The energy profile of the country has also been discussed.     

供需因素对城市内部房价分异的作用机理研究

以供需理论为切入点,基于个体居住选择和社会制度两方面构建住房价格空间分异的作用机理框架。在此基础上,分别从住房供给和住房需求两个角度分析城市内部房价分异的驱动因素和作用机制,以期为促进住房市场可持续健康发展提供参考。     

Comparison of solar radiation data sources for design and performance appraisal of CSP systems in India

The choice of a solar radiation data source is expected to have a significant impact on the predicted performance of a concentrating solar power (CSP) system and consequently on its technical and financial feasibility. In the present study, an attempt has been made to analyse the effect of choice of various solar radiation data sources on the predicted performance of a CSP system at 13 different locations in 5 different climatic zones of India. It was observed that there is significant variation in the amount of annual electricity output obtained for various locations using different solar radiation data sources resulting in variations in levelised cost of electricity. For a 50-MW parabolic trough-based CSP plant located in Jaisalmer, the estimated value of annual electricity output varies from 63 to 124?GWh. For a CSP plant based on the central tower receiver technology, the corresponding range is from 106 to 145?GWh.     

Nitrates and bacterial distribution in rural domestic water supplies

The protection of underground water resources in an important facet of the Safe Drinking Water Act. Effective intervention strategy for active source protection requires up-to-date information on ground water quality and the knowledge of potential sources and causes of contamination. In the present study the state of well water supplies in rural East Texas was evaluated in order to develop a practical approach to surveying water sources in ‘back-country’ areas, which would allow the differentiation of natural from anthropogenic factors affecting water quality. The specific focus was on nitrates, their extent, causes and sources in rural well water. Data were processed using synographic mapping which permitted the comparison of the natural tendency in distribution of nitrates with the patterns induced by man's activities. Trend surface analysis of data indicated that the surveyed Tertiary and Quaternary sands were not naturally nitrate-rich. Localized and well-defined spots of nitrates, many times in excess of the background, were traceable to the anthropogenic sources. The study identified the characteristics of high risk wells.     

Values and goals as determinants of intended tenure choice

Housing choice and tenure choice have beenstudied from many different theoreticalperspectives and with a great variety ofmethodological approaches. In explaininghousing choice, researchers have shown theinfluence of both macrolevel (housing market,economic situation) and microlevel (age,income) factors. Relatively little attentionhas been given to motivational microlevelfactors such as goals and values. In thisarticle, the focus is on values and goals asdeterminants of housing choice. Therelationships between these motivationalfactors, other microlevel factors, and housingchoice are specified in an extended means-endmodel which is based on means-end theory. Theempirical validity of this extended model hasbeen partly assessed by using it to predictintended tenure choice. In the article,previous research on the motivations forhousing choice is discussed and the extendedmeans-end model is described. The empiricalresults of applying the model to intendedtenure choice are presented and discussed,while the assessment of the reliability of thevalue scales is also described.     

Renewal and Replacement in a Northamptonshire Village: Housing in Potterspury 1727–1910

Abstract

A quarter of all the houses that existed in 1727 in the Northamptonshire village of Potterspury survive today. This has been demonstrated from documentary evidence and from buildings survey work. The starting point is a map of 1727 which shows each building in detail in respect of the number of storeys and bays and also of the positions of windows, doors and chimneys. The sketches of the houses on the 1727 map when compared with the existing surviving houses show much similar or identical detail. By supplementing the map evidence with evidence from other contemporary documents, a complete picture of the 1727 village has been reconstructed. Following this picture through the later documentary sources and by examining the nature of the surviving and lost buildings, it has been possible to establish a full history of each house. This paper covers the period from 1727 to 1910 and identifies the main periods during which houses in the village of Potterspury were lost. The factors leading to those losses and the nature of the new and the replacement houses are also identified.     

Substitution of piped water and self-supplied groundwater: The case of residential water in South Africa

The choice of water for use by residential households is usually limited to the centralized and more regulated piped water or the decentralized and less regulated groundwater sources. Many households secure access to water through self-supply from groundwater sources, consequently putting the resource at risk. Our analysis shows empirical evidence on the determinants of households’ choice of water-supply sources and suggests a high substitution threshold for piped water and self-supplied groundwater in South Africa. Furthermore, we provide insights into the potential welfare impact of a stylized piped water tariff change that reduces prices and leads to increased piped water choices.