Cardiac angiogenic imbalance leads to peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.     

Apolipoprotein E controls cerebrovascular integrity via cyclophilin A

Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4. APOE4 is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage. Neurovascular dysfunction is present in normal APOE4 carriers and individuals with APOE4-associated disorders. In mice, lack of Apoe leads to blood-brain barrier (BBB) breakdown, whereas APOE4 increases BBB susceptibility to injury. How APOE genotype affects brain microcirculation remains elusive. Using different APOE transgenic mice, including mice with ablation and/or inhibition of cyclophilin A (CypA), here we show that expression of APOE4 and lack of murine Apoe, but not APOE2 and APOE3, leads to BBB breakdown by activating a proinflammatory CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes. This, in turn, leads to neuronal uptake of multiple blood-derived neurotoxic proteins, and microvascular and cerebral blood flow reductions. We show that the vascular defects in Apoe-deficient and APOE4-expressing mice precede neuronal dysfunction and can initiate neurodegenerative changes. Astrocyte-secreted APOE3, but not APOE4, suppressed the CypA-nuclear factor-κB-matrix-metalloproteinase-9 pathway in pericytes through a lipoprotein receptor. Our data suggest that CypA is a key target for treating APOE4-mediated neurovascular injury and the resulting neuronal dysfunction and degeneration.     

珠江口亚热带红树真菌的初步探讨

对珠江中的亚热带红树林真菌作初步探讨．结果显示，在香港，澳门与深圳福田保护区的亚热带红树真菌的品种类型及丰富度与热带相似．但占优势的品种则有所不同．在２６０多块的漂浮木上，共发现了７６种真菌，包括４６种子囊菌，２６种半知菌与４种担子菌．其中占优势的有Ｔｒｉｃｈｏｃｌａｄｉｕｍｌｉｎｄｅｒｅｅ（１８％）Ｍａｒｉｎｏｓｐｈａｅｒａｍａｎｇｒｏｖｅｉ（１３％），Ｌｉｇｎｉｎｃｏｌａｌａｅｖｅｓ（１３％）和Ｈｙｐｏｘｙｌｉｎｏｃｅａｎｉｃｕｍ（１１％）；较少的包括Ｐｈｏｍｏｐｓｉｓｓｐ．（５％），Ｐｈｏｍａｓｐ，（６％），Ｈａｌｏｓａｒｐｈｅｉａａｂｏｎｎｅｓ（６％），Ｃｉｒｒｅｎａｌｉａｓｐ．（５％）．Ｓａｖｏｒｙｅｌｌａｌｉｇｎｉｃｏｌａ（５％）等。在被发现的真菌中，有数个是新品种，例如Ｍａｓｓａｒｉｎａａｒｍａｔｉｓｐｏｒａ，Ｄｉａｐｏｒｔｈｅｓａｌｓｕｇｉｎｏｓａ，Ａｎｉｐｔｏｄｅｒａｈａｉｓｐｏｒａ，Ｍｅｌａｓｐｉｌｅａｓｐ．和Ｐｌｅｏｓｐｏｒａｓｐ．等．     

煤层注水效果的数量化理论预测法与参数的修正

本文应用数量化理论，给出了如何建立煤层注水效果的预测数学模型，并结合实例，进行了预测．实例表明，根据本矿已知煤层注水工程的各种信息，采用数量化理论．建立的计算机预测煤层注水效果的方法，不仅可以确切地判定所给定的注水组合参数是否最优，同时还揭露了注水参数与水分增值的内在关系，为调控参数提供了科学手段     

高校图书馆电子图书借阅服务实证调研——以四川大学为例

以四川大学为例,通过对高校图书馆电子图书借阅服务情况的调研,分析了高校图书馆在开展电子图书借阅服务时存在的阅读条件限制、揭示不够及借阅模式尚不成熟等问题,提出了丰富揭示途径、优化阅读条件及进一步完善电子图书借阅服务的建议。     

Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder

Epithelial integrity in metazoan organs is maintained through the regulated proliferation and differentiation of organ-specific stem and progenitor cells. Although the epithelia of organs such as the intestine regenerate constantly and thus remain continuously proliferative, other organs, such as the mammalian urinary bladder, shift from near-quiescence to a highly proliferative state in response to epithelial injury. The cellular and molecular mechanisms underlying this injury-induced mode of regenerative response are poorly defined. Here we show in mice that the proliferative response to bacterial infection or chemical injury within the bladder is regulated by signal feedback between basal cells of the urothelium and the stromal cells that underlie them. We demonstrate that these basal cells include stem cells capable of regenerating all cell types within the urothelium, and are marked by expression of the secreted protein signal Sonic hedgehog (Shh). On injury, Shh expression in these basal cells increases and elicits increased stromal expression of Wnt protein signals, which in turn stimulate the proliferation of both urothelial and stromal cells. The heightened activity of this signal feedback circuit and the associated increase in cell proliferation appear to be required for restoration of urothelial function and, in the case of bacterial injury, may help clear and prevent further spread of infection. Our findings provide a conceptual framework for injury-induced epithelial regeneration in endodermal organs, and may provide a basis for understanding the roles of signalling pathways in cancer growth and metastasis.     

PDGF signalling controls age-dependent proliferation in pancreatic β-cells

Determining the signalling pathways that direct tissue expansion is a principal goal of regenerative biology. Vigorous pancreatic β-cell replication in juvenile mice and humans declines with age, and elucidating the basis for this decay may reveal strategies for inducing β-cell expansion, a long-sought goal for diabetes therapy. Here we show that platelet-derived growth factor receptor (Pdgfr) signalling controls age-dependent β-cell proliferation in mouse and human pancreatic islets. With age, declining β-cell Pdgfr levels were accompanied by reductions in β-cell enhancer of zeste homologue 2 (Ezh2) levels and β-cell replication. Conditional inactivation of the Pdgfra gene in β-cells accelerated these changes, preventing mouse neonatal β-cell expansion and adult β-cell regeneration. Targeted human PDGFR-α activation in mouse β-cells stimulated Erk1/2 phosphorylation, leading to Ezh2-dependent expansion of adult β-cells. Adult human islets lack PDGF signalling competence, but exposure of juvenile human islets to PDGF-AA stimulated β-cell proliferation. The discovery of a conserved pathway controlling age-dependent β-cell proliferation indicates new strategies for β-cell expansion.     

The role of dyking and fault control in the rapid onset of eruption at Chaitén volcano, Chile

Rhyolite is the most viscous of liquid magmas, so it was surprising that on 2?May 2008 at Chaitén Volcano, located in Chile's southern Andean volcanic zone, rhyolitic magma migrated from more than 5?km depth in less than 4?hours (ref.?1) and erupted explosively with only two days of detected precursory seismic activity. The last major rhyolite eruption before that at Chaitén was the largest volcanic eruption in the twentieth century, at Novarupta volcano, Alaska, in 1912. Because of the historically rare and explosive nature of rhyolite eruptions and because of the surprisingly short warning before the eruption of the Chaitén volcano, any information about the workings of the magmatic system at Chaitén, and rhyolitic systems in general, is important from both the scientific and hazard perspectives. Here we present surface deformation data related to the Chaitén eruption based on radar interferometry observations from the Japan Aerospace Exploration Agency (JAXA) DAICHI (ALOS) satellite. The data on this explosive rhyolite eruption indicate that the rapid ascent of rhyolite occurred through dyking and that melt segregation and magma storage were controlled by existing faults.     

A disinhibitory microcircuit for associative fear learning in the auditory cortex

Learning causes a change in how information is processed by neuronal circuits. Whereas synaptic plasticity, an important cellular mechanism, has been studied in great detail, we know much less about how learning is implemented at the level of neuronal circuits and, in particular, how interactions between distinct types of neurons within local networks contribute to the process of learning. Here we show that acquisition of associative fear memories depends on the recruitment of a disinhibitory microcircuit in the mouse auditory cortex. Fear-conditioning-associated disinhibition in auditory cortex is driven by foot-shock-mediated cholinergic activation of layer 1 interneurons, in turn generating inhibition of layer 2/3 parvalbumin-positive interneurons. Importantly, pharmacological or optogenetic block of pyramidal neuron disinhibition abolishes fear learning. Together, these data demonstrate that stimulus convergence in the auditory cortex is necessary for associative fear learning to complex tones, define the circuit elements mediating this convergence and suggest that layer-1-mediated disinhibition is an important mechanism underlying learning and information processing in neocortical circuits.