148 research outputs found

    Vulnerability of vascular endothelium in lipopolysaccharide toxicity: effect of (acyl) carnitine on endothelial stability

    Get PDF
    The literature presented illustrates that lipopolysaccharide (LPS), from bacterial cell walls, induces tumour necrosis factor (TNF) synthesis in macrophages. TNF affects a number of cell types, amongst which are endothelial cells, within a few hours. Its injection has been shown to produce all symptoms of the toxic syndrome. In the present communication the vulnerability of endothelial cells will be stressed. These cells require carnitine not only for fatty acid oxidation but also for membrane protection and repair. As endothelial cells lose carnitine during hypoperfusion, it is speculated that the supply of carnitine during the early phase of LPS toxicity in rats might delay or avoid loss of endothelial functions. Earlier it was observed that hearts from rats, injected 3 h previously with LPS, showed strongly increased interstitial fluid production compared to hearts from control rats, even when TNF was present during a 3 h in vitro perfusion. It showed that LPS in vivo generates factors other than TNF, such as platelet activating factor (PAF), that are responsible for the increased capillary permeability

    The Conserved Nup107-160 Complex Is Critical for Nuclear Pore Complex Assembly

    Get PDF
    AbstractNuclear pore complexes (NPCs) are large multiprotein assemblies that allow traffic between the cytoplasm and the nucleus. During mitosis in higher eukaryotes, the Nuclear Envelope (NE) breaks down and NPCs disassemble. How NPCs reassemble and incorporate into the NE upon mitotic exit is poorly understood. We demonstrate a function for the conserved Nup107-160 complex in this process. Partial in vivo depletion of Nup133 or Nup107 via RNAi in HeLa cells resulted in reduced levels of multiple nucleoporins and decreased NPC density in the NE. Immunodepletion of the entire Nup107-160 complex from in vitro nuclear assembly reactions produced nuclei with a continuous NE but no NPCs. This phenotype was reversible only if Nup107-160 complex was readded before closed NE formation. Depletion also prevented association of FG-repeat nucleoporins with chromatin. We propose a stepwise model in which postmitotic NPC assembly initiates on chromatin via early recruitment of the Nup107-160 complex

    Glycinergic interneurons are functionally integrated into the inspiratory network of mouse medullary slices

    Get PDF
    Neuronal activity in the respiratory network is functionally dependent on inhibitory synaptic transmission. Using two-photon excitation microscopy, we analyzed the integration of glycinergic neurons in the isolated inspiratory pre-Bötzinger complex-driven network of the rhythmic slice preparation. Inspiratory (96%) and ‘tonic’ expiratory neurons (4%) were identified via an increase or decrease, respectively, of the cytosolic free calcium concentration during the inspiratory-related respiratory burst. Furthermore, in BAC-transgenic mice expressing EGFP under the control of the GlyT2-promoter, 50% of calcium-imaged inspiratory neurons were glycinergic. Inspiratory bursting of glycinergic neurons in the slice was confirmed by whole-cell recording. We also found glycinergic neurons that receive phasic inhibition from other glycinergic neurons. Our calcium imaging data show that glycinergic neurons comprise a large population of inspiratory neurons in the pre-Bötzinger complex-driven network of the rhythmic slice preparation

    Shedding Light on Vampires: The Phylogeny of Vampyrellid Amoebae Revisited

    Get PDF
    With the advent of molecular phylogenetic techniques the polyphyly of naked filose amoebae has been proven. They are interspersed in several supergroups of eukaryotes and most of them already found their place within the tree of life. Although the ‘vampire amoebae’ have attracted interest since the middle of the 19th century, the phylogenetic position and even the monophyly of this traditional group are still uncertain. In this study clonal co-cultures of eight algivorous vampyrellid amoebae and the respective food algae were established. Culture material was characterized morphologically and a molecular phylogeny was inferred using SSU rDNA sequence comparisons. We found that the limnetic, algivorous vampyrellid amoebae investigated in this study belong to a major clade within the Endomyxa Cavalier-Smith, 2002 (Cercozoa), grouping together with a few soil-dwelling taxa. They split into two robust clades, one containing species of the genus Vampyrella Cienkowski, 1865, the other containing the genus Leptophrys Hertwig & Lesser, 1874, together with terrestrial members. Supported by morphological data these clades are designated as the two families Vampyrellidae Zopf, 1885, and Leptophryidae fam. nov. Furthermore the order Vampyrellida West, 1901 was revised and now corresponds to the major vampyrellid clade within the Endomyxa, comprising the Vampyrellidae and Leptophryidae as well as several environmental sequences. In the light of the presented phylogenetic analyses morphological and ecological aspects, the feeding strategy and nutritional specialization within the vampyrellid amoebae are discussed

    The ongoing pursuit of neuroprotective therapies in Parkinson disease

    Get PDF
    Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD

    Two views on neutral money: Wieser and Hayek versus Menger and Mises

    Get PDF
    Neutral money plays a central role in contemporary macroeconomic theory, and is a live issue in recent monetary policy discussions. We challenge the opinion that Hayek’s writings on neutral money have been influenced by, and are similar to, the work of Menger and Mises. We show, first, the significant alternative influence of Friedrich von Wieser on Hayek’s work on the subject. Second, we rehabilitate a neglected method of monetary theorizing specific to Menger and Mises that rejects money neutrality both as a tool for investigating monetary phenomena and as the standard by which monetary regimes, and the market economy itself, should be evaluated. Examining this chapter in the history of economic thought can aid in a deeper reconsideration of the doctrinal foundations of modern monetary theory and policy

    Temporal dynamics of microbiota before and after host death

    Get PDF
    The habitats that animals, humans and plants provide for microbial communities are inevitably transient, changing drastically when these hosts die. Because microbes associated with living hosts are ensured prime access to the deceased host's organic matter, it is feasible that opportunistic, adaptable lifestyles are widespread among host-associated microbes. Here we investigate the temporal dynamics of microbiota by starving to death a host-the planktonic Crustacean Daphnia magna-and tracking the changes in its microbial community as it approaches death, dies and decomposes. Along with obligate host-associated microbes that vanished after the host's death and decomposers that appeared after the host's death, we also detected microbes with opportunistic lifestyles, seemingly capable of exploiting the host even before its death. We suggest that the period around host death plays an important role for host-microbiota ecology and for the evolution of hosts and their microbes
    corecore