Plasminogen activator inhibitor-1 deficient mice are protected from angiotensin II-induced fibrosis

PAI-1 has been shown to be both profibrotic and antifibrotic in animal models of hepatic fibrosis. Although these models have similarities to human fibrotic liver disease, no rodent model completely recapitulates the clinical situation; indeed, transaminase values in most models of hepatic fibrosis are much higher than in chronic liver diseases in humans. Here, wild-type and PAI-1^−/− mice were administered AngII (500 ng/kg/min) for 4 weeks. ECM accumulation was evaluated by Sirius red staining, hydroxyproline content, and fibrin and collagen immunostaining. Induction of pro-fibrotic genes was assessed by real-time RT-PCR. Despite the absence of any significant liver damage, AngII infusion increased the deposition of hepatic collagen and fibrin ECM, with a perisinusoidal pattern. PAI-1^−/− mice were protected from these ECM changes, indicating a causal role of PAI-1 in this fibrosis model. Protection in the knockout strain correlated with a blunted increase in αSMA, and elevated activities of matrix metalloproteinases (MMP2, MMP9). These data suggest that PAI-1 plays a critical role in mediating fibrosis caused by AngII and lends weight-of-evidence to a pro-fibrotic role of this protein in liver. Furthermore, the current study proposes a new model of ‘pure’ hepatic fibrosis in mice with little inflammation or hepatocyte death.     

心脏特异表达LMNA^E82K转基因小鼠的建立

目的建立心脏特异表达LMNAE82K转基因小鼠,为研究LMNAE82K与心肌病发病机制的关系提供工具动物。方法把LMNAE82K基因插入α-MHC启动子下游,构建转基因表达载体,显微注射法建立C57BL/6JLMNAE82K转基因小鼠,PCR鉴定转基因小鼠的基因型,采用Western Blot鉴定LMNAE82K在心脏组织中的表达,H＆E染色和超声检测转基因小鼠心脏的病理改变。结果建立了2个心脏组织特异表达LMNAE82K的转基因小鼠品系。超声检查显示转基因小鼠心室壁变薄,收缩期容积和舒张期容积增加,射血分数及短轴缩短率降低。结论LMNAE82K转基因小鼠具有LMNAE82K引起的家族性扩心病有类似的病理变化,为研究LMNAE82K与心肌病发病机制的关系的研究提供了有价值的疾病动物模型。     

东亚飞蝗hunchback基因在卵子形成和胚胎发育过程中的原位表达

hb（hunchback）基因是昆虫胚胎前后轴模式形成的关键基因．对东亚飞蝗（Locusta migratoria manilensis,Meyen）hb基因的功能已有报道,但其表达模式还不清楚．为了研究胁基因在东亚飞蝗卵子形成和胚胎发育过程中的时空表达情况,本研究采用免疫组化方法在蛋白质水平上检测了hb基因的时空表达模式．在卵子形成过程中,hb基因局限在卵细胞核区中表达,随着卵子的发育逐渐移至卵细胞的后端;卵受精后,核区里的Hb蛋白向外扩散,在卵后端形成浓度梯度;胚盘期,hb基因在胚盘中央呈带状表达;胚盘分化为原头和原躯干后,表达条带变宽,并呈现出梯度表达,该表达区域将形成颌、胸部的部分体节;随着腹节开始形成,hb基因在颌胸部的表达逐渐减弱,而在腹部后端的“生长区”表达,并呈现出不连续性．经比较,hb易基因在昆虫颌胸部的表达较为保守,而在卵子形成过程中和腹部的表达具有较大的变异性．与黑腹果蝇等长胚带昆虫相比,东亚飞蝗hb基因在体节形成的基因级联调控中具有更重要、更直接的调控作用．     

Global transcriptional response of pig brain and lung to natural infection by Pseudorabies virus

Background  

Pseudorabies virus (PRV) is an alphaherpesviruses whose native host is pig. PRV infection mainly causes signs of central nervous system disorder in young pigs, and respiratory system diseases in the adult.     

Stratigraphy and palaeoenvironmental implications of Pleistocene and Holocene aeolian sediments in the Lhasa area,southern Tibet (China)

Along the middle and lower reaches of the Kyichu River and its tributaries (Lhasa area, southern Tibet), a multidisciplinary study was carried out in order to investigate the areal distribution, sedimentological properties, ages and palaeoenvironmental implications of aeolian deposits including intercalated palaeosols. This research was initiated to investigate to what extent southern Tibet is influenced by past human activity, as even recent evaluations perceive the present treeless desertic environment as natural. Fifteen profiles were recorded at an altitude of 3540–4580 m a.s.l. with subsequent sedimentological, geochronological (OSL, AMS ¹⁴C) and palaeobotanical (charcoal) analyses. Sediment properties of both loesses and aeolian sands reveal an origin from aeolian sorting of nearby fluvial deposits. The calculated ages are the oldest obtained thus far on aeolian sediments from southern and interior Tibet, revealing natural aeolian sedimentation before and around the Last Glacial Maximum (c. 20 ka). However, a distinct portion of Late Holocene sandy aeolian sediments also occurs. Both the evidence for the aeolian dynamics (widespread Pleistocene loess and aeolian sand deposition, local Late Holocene aeolian sand deposition, modern reactivation of widespread Pleistocene aeolian sands) and the palaeobotanical findings (Late Holocene vegetation change from a tree-bearing to a widely treeless landscape) provide evidence that the Lhasa area was strongly influenced by human activity since at least the Late Neolithic (c. 4200 cal yrs BP). Thus the present-day desertic environment might not primarily be a result of the semiarid climate or the high-altitude conditions, but rather of activities of the humans and their collateral effects. However, once established, this semi-natural ecosystem persisted, controlled by strong grazing, firewood extraction, erosion and harsh edaphic conditions, preventing the recovery of trees.     

Budburst and leaf area expansion measured with a novel mobile camera system and simple color thresholding

Plant phenology relates strongly to primary productivity and the energy that enters into ecological food webs, and thus is vital in understanding ecosystem function and the effects of climate and climate change. The manual collection of phenological data is labor-intensive and not easily scalable, thus the ability to quantify leaf flush and other parameters at many locations requires innovative new methodologies such as the use of visible light digital cameras. Improved imaging performance was obtained by using a cabled, mobile camera system that allowed a repeated image census of branches of Rhododendron occidentale in the understory along a 30 m transect during leaf flush. Automatic division of acquired images into areas of interest (leaves) and background for calculating leaf area was accomplished by thresholding images in different color spaces. Transformation of the color space into the hue, saturation, and luminance (HSL) color space before thresholding resulted in a mean RMS error of 21.2 cm² compared to hand-counts of leaf area. Thresholding in the native red, green, and blue (RGB) color space to isolate leaves resulted in a larger error, as did using algebraic combinations of the color components or color ratios. Relating physiological function to images, as for sap flow for branches of R. occidentale, indicates that the greening and calculated leaf area of a species as detected by imagers requires additional meteorological sensor data for interpretation.     

γ-Pyrone natural products—A privileged compound class provided by nature

In “Biology Oriented Synthesis” (BIOS), the inherent biological relevance of natural products is employed for the design and synthesis of compound libraries. Towards this end, library generation in BIOS is focused on compound classes from biologically relevant space such as the natural product space or also the drug space and only scaffolds of these areas of proven relevance are employed for synthesis of small focused libraries with limited diversity. We here present a short overview of γ-pyrone natural products, highlighting their biological properties and their potential applicability in a BIOS of a compound library.     

Selectivity profiling of DegP substrates and inhibitors

Protein quality control factors are involved in many key physiological processes and severe human diseases that are based on misfolding or amyloid formation. Prokaryotic representatives are often virulence factors of pathogenic bacteria. Therefore, protein quality control factors represent a novel class of drug targets. The bacterial serine protease DegP, belonging to the widely conserved family of HtrA proteases, exhibits unusual structural and functional plasticity that could be exploited by small molecule modulators. However, only one weak synthetic peptide substrate and no inhibitors are available to date. We report the identification of a potent heptameric pNA-substrate and chloromethyl ketone based inhibitors of DegP. In addition, specificity profiling resulted in the identification of one strong inhibitor and a potent substrate for subtilisin as well as a number of specific elastase substrates and inhibitors.     

PECAM-1 expression and activity negatively regulate multiple platelet signaling pathways

Platelet endothelial cell adhesion molecule-1 (PECAM-1) inhibits platelet response to collagen and may also inhibit two other major platelet agonists ADP and thrombin although this has been less well explored. We hypothesized that the combined effect of inhibiting these three platelet activating pathways may act to significantly inhibit thrombus formation. We demonstrate a negative relationship between PECAM-1 surface expression and platelet response to cross-linked collagen related peptide (CRP-XL) and ADP, and an inhibitory effect of PECAM-1 clustering on platelet response to CRP-XL, ADP and thrombin. This combined inhibition of multiple signaling pathways results in a marked reduction in thrombus formation.