颗粒间作用力影响颗粒体系流变性能的研究进展

悬浮颗粒体系在许多工业中都能见到踪影, 比如矿物加工、水和废水处理、陶瓷加工、造纸、食品加工工业等. 对于胶体颗粒悬浮体系, 颗粒间的相互作用力是控制体系的剪切流变性能、密实化性能和沉积性能的关键因素^[1,2]. 当颗粒间的作用力为排斥力时(排斥性颗粒体系), 颗粒不易“抱团”, 颗粒体系在溶液中处于稳定的分散状态. 而由于布朗热运动的作用, 颗粒的沉降速度很小. 不过, 对于这样的体系, 一旦颗粒最终都沉降下来形成颗粒网络就很密实; 而且即使在较低的外压下被压缩, 沉积层也很容易达到较高的固体体积比率(含水量少). 排斥性颗粒体系的黏度很低, 剪切流变抗力很小. 反之, 如果颗粒间的作用力是吸引力(吸引性颗粒体系), 颗粒就极易形成团块. 团块一般包含很多单个颗粒, 质量较大, 因此团块的沉降速度比单个颗粒快得多. 由此形成的颗粒网络的性质完全与排斥性颗粒体系相反: 它的密度低、含水量高, 需要更高的外压力才能密实化; 而且颗粒网络的黏度高, 剪切流变抗力较高^[3].     

A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality

Epigenetic information is frequently erased near the start of each new generation. In some cases, however, epigenetic information can be transmitted from parent to progeny (multigenerational epigenetic inheritance). A particularly notable example of this type of epigenetic inheritance is double-stranded RNA-mediated gene silencing in Caenorhabditis elegans. This RNA-mediated interference (RNAi) can be inherited for more than five generations. To understand this process, here we conduct a genetic screen for nematodes defective in transmitting RNAi silencing signals to future generations. This screen identified the heritable RNAi defective 1 (hrde-1) gene. hrde-1 encodes an Argonaute protein that associates with small interfering RNAs in the germ cells of progeny of animals exposed to double-stranded RNA. In the nuclei of these germ cells, HRDE-1 engages the nuclear RNAi defective pathway to direct the trimethylation of histone H3 at Lys?9 (H3K9me3) at RNAi-targeted genomic loci and promote RNAi inheritance. Under normal growth conditions, HRDE-1 associates with endogenously expressed short interfering RNAs, which direct nuclear gene silencing in germ cells. In hrde-1- or nuclear RNAi-deficient animals, germline silencing is lost over generational time. Concurrently, these animals exhibit steadily worsening defects in gamete formation and function that ultimately lead to sterility. These results establish that the Argonaute protein HRDE-1 directs gene-silencing events in germ-cell nuclei that drive multigenerational RNAi inheritance and promote immortality of the germ-cell lineage. We propose that C. elegans use the RNAi inheritance machinery to transmit epigenetic information, accrued by past generations, into future generations to regulate important biological processes.     

A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response

Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors, has not been fully explored. Here we use genetically engineered mouse models to conduct a 'co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244) increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors, markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies.     

Greenhouse gas mitigation can reduce sea-ice loss and increase polar bear persistence

On the basis of projected losses of their essential sea-ice habitats, a United States Geological Survey research team concluded in 2007 that two-thirds of the world's polar bears (Ursus maritimus) could disappear by mid-century if business-as-usual greenhouse gas emissions continue. That projection, however, did not consider the possible benefits of greenhouse gas mitigation. A key question is whether temperature increases lead to proportional losses of sea-ice habitat, or whether sea-ice cover crosses a tipping point and irreversibly collapses when temperature reaches a critical threshold. Such a tipping point would mean future greenhouse gas mitigation would confer no conservation benefits to polar bears. Here we show, using a general circulation model, that substantially more sea-ice habitat would be retained if greenhouse gas rise is mitigated. We also show, with Bayesian network model outcomes, that increased habitat retention under greenhouse gas mitigation means that polar bears could persist throughout the century in greater numbers and more areas than in the business-as-usual case. Our general circulation model outcomes did not reveal thresholds leading to irreversible loss of ice; instead, a linear relationship between global mean surface air temperature and sea-ice habitat substantiated the hypothesis that sea-ice thermodynamics can overcome albedo feedbacks proposed to cause sea-ice tipping points. Our outcomes indicate that rapid summer ice losses in models and observations represent increased volatility of a thinning sea-ice cover, rather than tipping-point behaviour. Mitigation-driven Bayesian network outcomes show that previously predicted declines in polar bear distribution and numbers are not unavoidable. Because polar bears are sentinels of the Arctic marine ecosystem and trends in their sea-ice habitats foreshadow future global changes, mitigating greenhouse gas emissions to improve polar bear status would have conservation benefits throughout and beyond the Arctic.     

南药巴戟天化学成分

为研究巴戟天药材的化学成分.通过硅胶柱色谱和ODS柱色谱等方法对其分离纯化,根据理化性质和光谱数据进行了结构鉴定.从巴戟天药材的乙醇提取物中分离得到了7个化合物,分别为1, 2-二氧乙烯蒽醌(1)、1, 3-二羟基-2-丁酰基蒽醌(2)、1, 2-二羟基蒽醌(3)、β-谷甾醇(4)、3β, 20 (R),丁基-5-烯基-胆甾醇(5)、3β, 5-烯基螺旋甾(6)、水晶兰苷(7),其中化合物1、2、5、6属于首次从该植物中分离得到.     

Hemoglobin as a source of iron overload in multiple sclerosis: does multiple sclerosis share risk factors with vascular disorders?

Although iron is known to be essential for the normal development and health of the central nervous system, abnormal iron deposits are found in and around multiple sclerosis (MS) lesions that themselves are closely associated with the cerebral vasculature. However, the origin of this excess iron is unknown, and it is not clear whether this is one of the primary causative events in the pathogenesis of MS, or simply another consequence of the long-lasting inflammatory conditions. Here, applying a systems biology approach, we propose an additional way for understanding the neurodegenerative component of the disease caused by chronic subclinical extravasation of hemoglobin, in combination with multiple other factors including, but not limited to, dysfunction of different cellular protective mechanisms against extracellular hemoglobin reactivity and oxidative stress. Moreover, such considerations could also shed light on and explain the higher susceptibility of MS patients to a wide range of cardiovascular disorders.     

Is it possible to find an econometric law that works well in explanation and prediction? The case of Australian money demand

Pratt and Schlaifer's (1984, 1988) research employed in efforts to produce laws in economics are considered and their use in predicting future data is described. Data for Australia are used to illustrate the approaches.     

Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype

Understanding the molecular underpinnings of cancer is of critical importance to the development of targeted intervention strategies. Identification of such targets, however, is notoriously difficult and unpredictable. Malignant cell transformation requires the cooperation of a few oncogenic mutations that cause substantial reorganization of many cell features and induce complex changes in gene expression patterns. Genes critical to this multifaceted cellular phenotype have therefore only been identified after signalling pathway analysis or on an ad hoc basis. Our observations that cell transformation by cooperating oncogenic lesions depends on synergistic modulation of downstream signalling circuitry suggest that malignant transformation is a highly cooperative process, involving synergy at multiple levels of regulation, including gene expression. Here we show that a large proportion of genes controlled synergistically by loss-of-function p53 and Ras activation are critical to the malignant state of murine and human colon cells. Notably, 14 out of 24 'cooperation response genes' were found to contribute to tumour formation in gene perturbation experiments. In contrast, only 1 in 14 perturbations of the genes responding in a non-synergistic manner had a similar effect. Synergistic control of gene expression by oncogenic mutations thus emerges as an underlying key to malignancy, and provides an attractive rationale for identifying intervention targets in gene networks downstream of oncogenic gain- and loss-of-function mutations.