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991.
Zebrafish are becoming increasingly popular as an organism in which to model human disease and to study the effects of small molecules on complex physiological and pathological processes. Since larvae are no more than a few millimetres in length, and can live in volumes as small as 100 microliters, they are particularly amenable to high-throughput and high content compound screening in 96 well plate format. There is a growing literature providing evidence that many compounds show similar pharmacological effects in zebrafish as they do in mammals, and in particular humans. However, a major question regarding their utility for small molecule screening for neurological conditions is whether a molecule will reach its target site within the central nervous system. Studies have shown that Claudin-5 and ZO-1, tight-junction proteins which are essential for blood-brain barrier (BBB) integrity in mammals, can be detected in some cerebral vessels in zebrafish from 3 days post-fertilisation (d.p.f.) onwards and this timing coincides with the retention of dyes, immunoreactive tracers and fluorescent markers within some but not all cerebral vessels. Whilst these findings demonstrate that features of a BBB are first present at 3 d.p.f., it is not clear how quickly the zebrafish BBB matures or how closely the barrier resembles that of mammals. Here, we have combined anatomical analysis by transmission electron microscopy, functional investigation using fluorescent markers and compound uptake using liquid chromatography/tandem mass spectrometry to demonstrate that maturation of the zebrafish BBB occurs between 3 d.p.f. and 10 d.p.f. and that this barrier shares both structural and functional similarities with that of mammals. 相似文献
992.
Nora Mueller Elita Avota Lena Collenburg Heike Grassmé Sibylle Schneider-Schaulies 《PLoS pathogens》2014,10(12)
T cell paralysis is a main feature of measles virus (MV) induced immunosuppression. MV contact mediated activation of sphingomyelinases was found to contribute to MV interference with T cell actin reorganization. The role of these enzymes in MV-induced inhibition of T cell activation remained equally undefined as their general role in regulating immune synapse (IS) activity which relies on spatiotemporal membrane patterning. Our study for the first time reveals that transient activation of the neutral sphingomyelinase 2 (NSM2) occurs in physiological co-stimulation of primary T cells where ceramide accumulation is confined to the lamellum (where also NSM2 can be detected) and excluded from IS areas of high actin turnover. Genetic ablation of the enzyme is associated with T cell hyper-responsiveness as revealed by actin dynamics, tyrosine phosphorylation, Ca2+-mobilization and expansion indicating that NSM2 acts to suppress overshooting T cell responses. In line with its suppressive activity, exaggerated, prolonged NSM2 activation as occurring in co-stimulated T cells following MV exposure was associated with aberrant compartmentalization of ceramides, loss of spreading responses, interference with accumulation of tyrosine phosphorylated protein species and expansion. Altogether, this study for the first time reveals a role of NSM2 in physiological T cell stimulation which is dampening and can be abused by a virus, which promotes enhanced and prolonged NSM2 activation to cause pathological T cell suppression. 相似文献
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Invasions by introduced ant species can be ecologically destructive and affect a wide range of taxa, particularly native ants. Invasive ant species often numerically dominate ant communities and outperform native ant species in effective resource acquisition. Here, we describe interactions between the invasive ant Anoplolepis gracilipes (Smith) and resident ant species in disturbed habitats in NE Borneo. We measured interference competition abilities of A. gracilipes by performing arena bioassays between two A. gracilipes colonies and seven local ant species, and measured its effective resource competition at baits within supercolonies and at supercolony boundaries. Furthermore, we compared ant species diversity and composition at baits among (A) core areas of A. gracilipes supercolonies, (B) supercolony boundaries and (C) outside supercolonies. Anoplolepis gracilipes was behaviorally dominant over most ant species except Oecophylla smaragdina. Within supercolonies, A. gracilipes discovered all food baits first, and monopolized the vast majority throughout the course of the experiment. At supercolony boundaries, A. gracilipes discovered baits later than resident ant species, but subsequently monopolized half of the baits. Furthermore, the activity and diversity of the ant community within A. gracilipes supercolonies was lower than at its boundaries and outside supercolonies, and the ant communities differed significantly between infested and noninfested areas. Our study supports the hypothesis that successful establishment of A. gracilipes in anthropogenically disturbed habitats may negatively affect resident ant communities through high levels of direct interspecific aggression and almost complete monopolization of resources within high‐density supercolonies. 相似文献
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Tetsuya Shiga Heike Althen Miriam Cornella Katarzyna Zarnowiec Hirooki Yabe Carles Escera 《PloS one》2015,10(9)
The mismatch negativity (MMN) provides a correlate of automatic auditory discrimination in human auditory cortex that is elicited in response to violation of any acoustic regularity. Recently, deviance-related responses were found at much earlier cortical processing stages as reflected by the middle latency response (MLR) of the auditory evoked potential, and even at the level of the auditory brainstem as reflected by the frequency following response (FFR). However, no study has reported deviance-related responses in the FFR, MLR and long latency response (LLR) concurrently in a single recording protocol. Amplitude-modulated (AM) sounds were presented to healthy human participants in a frequency oddball paradigm to investigate deviance-related responses along the auditory hierarchy in the ranges of FFR, MLR and LLR. AM frequency deviants modulated the FFR, the Na and Nb components of the MLR, and the LLR eliciting the MMN. These findings demonstrate that it is possible to elicit deviance-related responses at three different levels (FFR, MLR and LLR) in one single recording protocol, highlight the involvement of the whole auditory hierarchy in deviance detection and have implications for cognitive and clinical auditory neuroscience. Moreover, the present protocol provides a new research tool into clinical neuroscience so that the functional integrity of the auditory novelty system can now be tested as a whole in a range of clinical populations where the MMN was previously shown to be defective. 相似文献
999.
Annika Wiebring Heike Helmholz Ilka Sötje Stephan Lassen Andreas Prange Henry Tiemann 《Marine biotechnology (New York, N.Y.)》2010,12(3):308-317
Jellyfish have an increasing impact on marine ecology. Cnidocysts bearing stinging cells afford, amongst others, prey capture
and defence. Several different types of stinging capsules are found in one species and they are supposed to have specific
functions, e.g. paralysing prey or adhering to it. Due to these assumed different roles of the capsules, it is suggested that
toxins, which are contained in the capsules, differ in composition. Analysis of distinct types of nematocysts requires an
appropriate method for the separation of the different types. Mixtures of types of nematocysts were obtained of two species
of jellyfish, Aurelia aurita and Cyanea lamarckii, by maceration of the tissue. These mixtures were treated with a method called laser microdissection and pressure catapulting
(LMPC). Optimized maceration methods, which were firstly introduced as a method for this purpose, in conjunction with optimized
LMPC parameters lead to sufficient amounts of separated capsules of individual types for subsequent mass-spectrometric analyses.
In case of A. aurita, the resulting mass spectra had some constituents in common, whereas in the overall pattern, the two distinct nematocyst
types differed. 相似文献
1000.
Heike Lindner Sharon A. Kessler Lena M. Müller Hiroko Shimosato-Asano Aurélien Boisson-Dernier Ueli Grossniklaus 《PLoS biology》2015,13(4)
Pollen tube (PT) reception in flowering plants describes the crosstalk between the male and female gametophytes upon PT arrival at the synergid cells of the ovule. It leads to PT growth arrest, rupture, and sperm cell release, and is thus essential to ensure double fertilization. Here, we describe TURAN (TUN) and EVAN (EVN), two novel members of the PT reception pathway that is mediated by the FERONIA (FER) receptor-like kinase (RLK). Like fer, mutations in these two genes lead to PT overgrowth inside the female gametophyte (FG) without PT rupture. Mapping by next-generation sequencing, cytological analysis of reporter genes, and biochemical assays of glycoproteins in RNAi knockdown mutants revealed both genes to be involved in protein N-glycosylation in the endoplasmic reticulum (ER). TUN encodes a uridine diphosphate (UDP)-glycosyltransferase superfamily protein and EVN a dolichol kinase. In addition to their common role during PT reception in the synergids, both genes have distinct functions in the pollen: whereas EVN is essential for pollen development, TUN is required for PT growth and integrity by affecting the stability of the pollen-specific FER homologs ANXUR1 (ANX1) and ANX2. ANX1- and ANX2-YFP reporters are not expressed in tun pollen grains, but ANX1-YFP is degraded via the ER-associated degradation (ERAD) pathway, likely underlying the anx1/2-like premature PT rupture phenotype of tun mutants. Thus, as in animal sperm–egg interactions, protein glycosylation is essential for the interaction between the female and male gametophytes during PT reception to ensure fertilization and successful reproduction. 相似文献