Characterization of the relationship between FLI1 and immune infiltrate level in tumour immune microenvironment for breast cancer

Breast cancer is the most common cancer and the leading cause of cancer death among women in the world. Tumour-infiltrating lymphocytes were defined as the white blood cells left in the vasculature and localized in tumours. Recently, tumour-infiltrating lymphocytes were found to be associated with good prognosis and response to immunotherapy in tumours. In this study, to examine the influence of FLI1 in immune system in breast cancer, we interrogated the relationship between the FLI1 expression levels with infiltration levels of 28 immune cell types. By splitting the breast cancer samples into high and low expression FLI1 subtypes, we found that the high expression FLI1 subtype was enriched in many immune cell types, and the up-regulated differentially expressed genes between them were enriched in immune system processes, immune-related KEGG pathways and biological processes. In addition, many important immune-related features were found to be positively correlated with the FLI1 expression level. Furthermore, we found that the FLI1 was correlated with the immune-related genes. Our findings may provide useful help for recognizing the relationship between tumour immune microenvironment and FLI1, and may unravel clinical outcomes and immunotherapy utility for FLI1 in breast cancer.     

拟南芥花药绒毡层细胞中具有基因簇特征的基因进化和功能分析

在植物基因组中, 除了同源基因成簇现象外, 近年来还发现一些具有共表达特性的异源基因也能够以基因簇形式存在, 但这些异源基因簇的进化和生物学功能尚不清楚。花药发育和花粉形成是植物进化出的特有的生殖生物学过程, 同时产生了一些在花药绒毡层中特异表达和特定功能的基因簇基因。该研究通过筛选和分析花药绒毡层中基因簇基因的分子特性、表达调控、基因年龄和基因重复进化等信息, 探讨花药基因簇基因与植物开花功能进化之间的关系。结果表明, 在拟南芥(Arabidopsis thaliana)中共筛选到84个(13个基因簇)花药绒毡层特异高表达的基因簇基因, 它们主要产生于串联重复事件, 76%的基因出现在开花植物分化后的阶段, 主要参与生殖发育、花粉鞘组成和脂代谢等生物学过程。研究初步解析了拟南芥花药绒毡层中基因簇基因的基本特征、生物学功能和基因进化机制, 为深入揭示植物基因簇基因的遗传学功能奠定了基础。     

Hypoxic postconditioning promotes mitophagy against transient global cerebral ischemia via PINK1/Parkin-induced mitochondrial ubiquitination in adult rats

Mitophagy alleviates neuronal damage after cerebral ischemia by selectively removing dysfunctional mitochondria. Phosphatase and tensin homolog (PTEN) induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy is the most well-known type of mitophagy. However, little is known about the role of PINK1/Parkin-mediated mitophagy in ischemic tolerance induced by hypoxic postconditioning (HPC) with 8% O₂ against transient global cerebral ischemia (tGCI). Hence, we aimed to test the hypothesis that HPC-mediated PINK1/Parkin-induced mitochondrial ubiquitination and promotes mitophagy, thus exerting neuroprotection in the hippocampal CA1 subregion against tGCI. We found that mitochondrial clearance was disturbed at the late phase of reperfusion after tGCI, which was reversed by HPC, as evidenced by the reduction of the translocase of outer mitochondrial membrane 20 homologs (TOMM20), translocase of inner mitochondrial membrane 23 (TIMM23) and heat shock protein 60 (HSP60) in CA1 after HPC. In addition, HPC further increased the ratio of LC3II/I in mitochondrial fraction and promoted the formation of mitophagosomes in CA1 neurons after tGCI. The administration of lysosome inhibitor chloroquine (CQ) intraperitoneally or mitophagy inhibitor (Mdivi-1) intracerebroventricularly abrogated HPC-induced mitochondrial turnover and neuroprotection in CA1 after tGCI. We also found that HPC activated PINK1/Parkin pathway after tGCI, as shown by the augment of mitochondrial PINK1 and Parkin and the promotion of mitochondrial ubiquitination in CA1. In addition, PINK1 or Parkin knockdown with small-interfering RNA (siRNA) suppressed the activation of PINK1/Parkin pathway and hampered mitochondrial clearance and attenuated neuroprotection induced by HPC, whereas PINK1 overexpression promoted PINK1/Parkin-mediated mitophagy and ameliorated neuronal damage in CA1 after tGCI. Taken together, the new finding in this study is that HPC-induced neuroprotection against tGCI through promoting mitophagy mediated by PINK1/Parkin-dependent pathway.Subject terms: Cell death in the nervous system, Stroke     

The Arabidopsis BE1 Gene, Encoding a Putative Glycoside Hydrolase Localized in Plastids, Plays Crucial Roles during Embryogenesis and Carbohydrate Metabolism

Carbohydrate metabolism is central to plant growth and development. However, little is known about its role in embryogenesis. Here, we report the characterization of multiple alleles of the BRANCHING ENZYME1 (BE1) gene (also known as EMB2729). The weak allele of be1-3, characterized by positional cloning, carries a single-nucleotide substitution in an exon-intron junction and shows various developmental defects during post-germination growth. This mutation causes a reduced level of BE1 mRNA that, likely generated from cryptically spliced pre-mRNA, contains a Glu-to-Lys substitution at codon 366. In four null alleles, BE1 is disrupted by T-DNA insertions, causing embryo developmental arrests at the heart stage. Light microscopy reveals reduced cell divisions and abnormal cell differentiation, thereby leading to defects in setting up the shoot apical meristem, embryonic vascular tissues and cotyledons. Overexpression of BE1 results in a pleiotropic phenotype, indicating that the fine-tuned BE1 level is crucial for plant growth and development. BE1 encodes a putative glycoside hydrolase that is highly conserved in higher plants. A BE1-GFP fusion protein, which is fully functional in complementing be1 mutants, is localized in plastids. The be1-3 phenotype can be partially rescued by glucose, fructose or sucrose, implying the involvement of BE1 in carbohydrate metabolism in plastids.     

Current perspectives in pulmonary surfactant--inhibition, enhancement and evaluation

Pulmonary surfactant (PS) is a complicated mixture of approximately 90% lipids and 10% proteins. It plays an important role in maintaining normal respiratory mechanics by reducing alveolar surface tension to near-zero values. Supplementing exogenous surfactant to newborns suffering from respiratory distress syndrome (RDS), a leading cause of perinatal mortality, has completely altered neonatal care in industrialized countries. Surfactant therapy has also been applied to the acute respiratory distress syndrome (ARDS) but with only limited success. Biophysical studies suggest that surfactant inhibition is partially responsible for this unsatisfactory performance. This paper reviews the biophysical properties of functional and dysfunctional PS. The biophysical properties of PS are further limited to surface activity, i.e., properties related to highly dynamic and very low surface tensions. Three main perspectives are reviewed. (1) How does PS permit both rapid adsorption and the ability to reach very low surface tensions? (2) How is PS inactivated by different inhibitory substances and how can this inhibition be counteracted? A recent research focus of using water-soluble polymers as additives to enhance the surface activity of clinical PS and to overcome inhibition is extensively discussed. (3) Which in vivo, in situ, and in vitro methods are available for evaluating the surface activity of PS and what are their relative merits? A better understanding of the biophysical properties of functional and dysfunctional PS is important for the further development of surfactant therapy, especially for its potential application in ARDS.     

Matrix metalloproteinase 13 (MMP13) and tissue inhibitor of matrix metalloproteinase 1 (TIMP1), regulated by the MAPK pathway, are both necessary for Madin-Darby canine kidney tubulogenesis

A classic model of tubulogenesis utilizes Madin-Darby canine kidney (MDCK) cells. MDCK cells form monoclonal cysts in three-dimensional collagen and tubulate in response to hepatocyte growth factor, which activates multiple signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway. It was shown previously that MAPK activation is necessary and sufficient to induce the first stage of tubulogenesis, the partial epithelial to mesenchymal transition (p-EMT), whereas matrix metalloproteinases (MMPs) are necessary for the second redifferentiation stage. To identify specific MMP genes, their regulators, tissue inhibitors of matrix metalloproteinases (TIMPs), and the molecular pathways by which they are activated, we used two distinct MAPK inhibitors and a technique we have termed subtraction pathway microarray analysis. Of the 19 MMPs and 3 TIMPs present on the Canine Genome 2.0 Array, MMP13 and TIMP1 were up-regulated 198- and 169-fold, respectively, via the MAPK pathway. This was confirmed by two-dimensional and three-dimensional real time PCR, as well as in MDCK cells inducible for the MAPK gene Raf. Knockdown of MMP13 using short hairpin RNA prevented progression past the initial phase of p-EMT. Knockdown of TIMP1 prevented normal cystogenesis, although the initial phase of p-EMT did occasionally occur. The MMP13 knockdown phenotype is likely because of decreased collagenase activity, whereas the TIMP1 knockdown phenotype appears due to increased apoptosis. These data suggest a model, which may also be important for development of other branched organs, whereby the MAPK pathway controls both MDCK p-EMT and redifferentiation, in part by activating MMP13 and TIMP1.     

Interaction between chitosan and bovine lung extract surfactants

The interaction between a cationic polyelectrolyte, chitosan, and an exogenous bovine lung extract surfactant (BLES) was studied using dynamic compression/expansion cycles of dilute BLES preparations in a Constrained Sessile Drop (CSD) device equipped with an environmental chamber conditioned at 37 °C and 100% R.H. air. Under these conditions, dilute BLES preparations tend to produce variable and relatively high minimum surface tensions. Upon addition of “low” chitosan to BLES ratios, the minimum surface tension of BLES-chitosan preparations were consistently low (i.e. < 5 mJ/m²), and the resulting surfactant monolayers (adsorbed at the air-water interface) were highly elastic and stable. However, the use of “high” chitosan to BLES ratios induced the collapse of the surfactant monolayer at high minimum surface tensions (i.e. > 15 mJ/m²). The zeta potential of the lung surfactant aggregates in the subphase suggests that chitosan binds to the anionic lipids (phosphatidyl glycerols) in BLES, and that this binding is ultimately responsible for the changes in the surface activity (elasticity and stability) of these surfactant-polyelectrolyte mixtures. Furthermore the transition from “low” to “high” chitosan to BLES ratios correlates with the flocculation and de-flocculation of surfactant aggregates in the subphase. It is proposed that the aggregation/segregation of “patches” of anionic lipids in the surfactant monolayer produced at different chitosan to BLES ratios explains the enhancing/inhibitory effects of chitosan. These observations highlight the importance of electrostatic interactions in lung surfactant systems.     

家蚁的危害及控制

该文运用环境调查、食物诱引与蚁巢饲养相结合的方法,研究了与室内卫生有关的主要蚂蚁种类及其危害,探讨了主要优势种小黄家蚁的发生规律,分析了家蚁控制策略及措施,并提出家蚁控制的研究方向。北京地区发现建筑物蚂蚁5属9种,其中小黄家蚁Monomorium pharaonis是优势种群之一。蚂蚁的危害主要为咬扰人体、传播病菌、污染环境和损坏建筑。小黄家蚁在北京1年发生2—3代;生活史中有卵、幼虫、蛹和成虫4个时期;25～27℃时,工蚁从卵到成虫约需37d,雌雄蚁发育历期40d左右;工蚁寿命60—70d,雄蚁不超过20d,雌蚁可长达270d;室内昼夜出没,午夜12点至凌晨4点为活动峰时;四季发生,2月和10月为高峰期。蚂蚁控制策略应以环卫预防为基础、物理控制为首要、化学防治为重点,辅以其他各种有效的治理措施。     

油酸对THP-1巨噬细胞源性泡沫细胞三磷酸腺苷结合盒转运体A1表达和胆固醇流出的影响

以THP 1巨噬细胞源性泡沫细胞为研究对象 ,观察油酸对THP 1巨噬细胞源性泡沫细胞胆固醇流出和三磷酸腺苷结合盒转运体A1(ABCA1)表达的影响 ,以探讨油酸对动脉粥样硬化发生发展的影响。用液体闪烁计数器检测细胞内胆固醇流出 ,高效液相色谱分析细胞内总胆固醇、游离胆固醇和胆固醇酯含量 ,运用逆转录多聚酶链反应和Western印迹分别检测ABCA1mRNA与ABCA1蛋白的表达 ,采用流式细胞术检测细胞平均ABCA1荧光强度。实验显示油酸引起THP 1巨噬细胞源性泡沫细胞总胆固醇、游离胆固醇与胆固醇酯呈时间依赖性增加 ,而ABCA1蛋白水平、细胞平均ABCA1荧光强度以及apoA I介导的胆固醇流出呈时间依赖性减少 ,细胞内胆固醇增多 ,但ABCA1mRNA没有明显变化。结果表明 ,油酸减少THP 1巨噬细胞源性泡沫细胞ABCA1蛋白水平 ,降低细胞内胆固醇流出 ,增加细胞内胆固醇聚积。