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101.
Ines Yang Daniel Eibach Friederike Kops Birgit Brenneke Sabrina Woltemate Jessika Schulze André Bleich Achim D. Gruber Sureshkumar Muthupalani James G. Fox Christine Josenhans Sebastian Suerbaum 《PloS one》2013,8(8)
The mouse pathobiont Helicobacter hepaticus can induce typhlocolitis in interleukin-10-deficient mice, and H. hepaticus infection of immunodeficient mice is widely used as a model to study the role of pathogens and commensal bacteria in the pathogenesis of inflammatory bowel disease. C57BL/6J Il10−/− mice kept under specific pathogen-free conditions in two different facilities (MHH and MIT), displayed strong differences with respect to their susceptibilities to H. hepaticus-induced intestinal pathology. Mice at MIT developed robust typhlocolitis after infection with H. hepaticus, while mice at MHH developed no significant pathology after infection with the same H. hepaticus strain. We hypothesized that the intestinal microbiota might be responsible for these differences and therefore performed high resolution analysis of the intestinal microbiota composition in uninfected mice from the two facilities by deep sequencing of partial 16S rRNA amplicons. The microbiota composition differed markedly between mice from both facilities. Significant differences were also detected between two groups of MHH mice born in different years. Of the 119 operational taxonomic units (OTUs) that occurred in at least half the cecum or colon samples of at least one mouse group, 24 were only found in MIT mice, and another 13 OTUs could only be found in MHH samples. While most of the MHH-specific OTUs could only be identified to class or family level, the MIT-specific set contained OTUs identified to genus or species level, including the opportunistic pathogen, Bilophila wadsworthia. The susceptibility to H. hepaticus-induced colitis differed considerably between Il10−/− mice originating from the two institutions. This was associated with significant differences in microbiota composition, highlighting the importance of characterizing the intestinal microbiome when studying murine models of IBD. 相似文献
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103.
Cristian Hernández Morales Marcelo J. Sturaro Pedro M. Sales Nunes Sebastian Lotzkat Pedro L.V. Peloso 《Cladistics : the international journal of the Willi Hennig Society》2020,36(3):301-321
Alopoglossidae is a family of Neotropical lizards composed of 23 species allocated in two genera (Alopoglossus and Ptychoglossus). There is a lack of knowledge about the phylogenetic relationships and systematics of this family. Published phylogenies that include alopoglossid species have very low taxon coverage within the family, and are usually based on limited character sampling. Considering these shortcomings, we infer the phylogenetic relationships of Alopoglossidae—including all but one species in the family—based on the combined analyses of DNA sequences and morphological characters. We use four loci (the mitochondrial 12S, 16S and ND4; the nuclear C-mos) and a matrix of 143 phenotypic characters from scutellation, tongue morphology, hemipenis morphology, and osteology. The dataset is analyzed with Maximum Parsimony, with four alternative weighting schemes: three under Extended Implied Weighting, and one with equal weighting. The respective resulting topologies are compared in a sensitivity analysis framework. Our analyses support the paraphyly of Ptychoglossus, with Alopoglossus nested within it. We provide an updated classification for the family, where Ptychoglossus Boulenger, 1890 is considered a junior synonym of Alopoglossus Boulenger, 1885. 相似文献
104.
Anke Doller Sebastian Schulz Josef Pfeilschifter Wolfgang Eberhardt 《Nucleic acids research》2013,41(19):9152-9167
The role of the mRNA-binding protein human antigen R (HuR) in stabilization and translation of AU-rich elements (ARE) containing mRNAs is well established. However, the trafficking of HuR and bound mRNA cargo, which comprises a fundamental requirement for the aforementioned HuR functions is only poorly understood. By administering different cytoskeletal inhibitors, we found that the protein kinase Cδ (PKCδ)-triggered accumulation of cytoplasmic HuR by Angiotensin II (AngII) is an actin-myosin driven process functionally relevant for stabilization of ARE-bearing mRNAs. Furthermore, we show that the AngII-induced recruitment of HuR and its bound mRNA from ribonucleoprotein particles to free and cytoskeleton bound polysomes strongly depended on an intact actomyosin cytoskeleton. In addition, HuR allocation to free and cytoskeletal bound polysomes is highly sensitive toward RNase and PPtase and structurally depends on serine 318 (S318) located within the C-terminal RNA recognition motif (RRM3). Conversely, the trafficking of the phosphomimetic HuRS318D, mimicking HuR phosphorylation at S318 by the PKCδ remained PPtase resistant. Co-immunoprecipitation experiments with truncated HuR proteins revealed that the stimulus-induced association of HuR with myosin IIA is strictly RNA dependent and mediated via the RRM3. Our data implicate a microfilament dependent transport of HuR, which is relevant for stimulus-induced targeting of ARE-bearing mRNAs from translational inactive ribonucleoprotein particles to polysomes. 相似文献
105.
CRISPRmap: an automated classification of repeat conservation in prokaryotic adaptive immune systems
Sita J. Lange Omer S. Alkhnbashi Dominic Rose Sebastian Will Rolf Backofen 《Nucleic acids research》2013,41(17):8034-8044
Central to Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas systems are repeated RNA sequences that serve as Cas-protein–binding templates. Classification is based on the architectural composition of associated Cas proteins, considering repeat evolution is essential to complete the picture. We compiled the largest data set of CRISPRs to date, performed comprehensive, independent clustering analyses and identified a novel set of 40 conserved sequence families and 33 potential structure motifs for Cas-endoribonucleases with some distinct conservation patterns. Evolutionary relationships are presented as a hierarchical map of sequence and structure similarities for both a quick and detailed insight into the diversity of CRISPR-Cas systems. In a comparison with Cas-subtypes, I-C, I-E, I-F and type II were strongly coupled and the remaining type I and type III subtypes were loosely coupled to repeat and Cas1 evolution, respectively. Subtypes with a strong link to CRISPR evolution were almost exclusive to bacteria; nevertheless, we identified rare examples of potential horizontal transfer of I-C and I-E systems into archaeal organisms. Our easy-to-use web server provides an automated assignment of newly sequenced CRISPRs to our classification system and enables more informed choices on future hypotheses in CRISPR-Cas research: http://rna.informatik.uni-freiburg.de/CRISPRmap. 相似文献
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107.
EMBO J
32
13, 1817–1828 doi:10.1038/emboj.2013.96; published online April262013During evolution, the mammalian brain massively expanded its size. However, the exact roles of distinct neural precursors, identified in the developing cortex during embryogenesis, for size expansion and surface folding (i.e., gyration) remain largely unknown. New findings by Nonaka-Kinoshita et al advance our understanding of embryonic neural precursor function by identifying cell type-selective functions for size expansion and folding, and challenge previously held concepts of mammalian brain development.Over the course of evolution, the mammalian brain massively expanded its size and complexity, which is believed to be responsible for an increase in cognitive functions and intellectual skills. The increase in brain size and number of cortical neurons is primarily due to an increased surface area by generating folds (gyrations) while the cortical thickness remained relatively constant (Lui et al, 2011). In the last decade, substantial progress has been made in identifying the cellular sources of cortex development. Using genetic lineage tracing of individual cell populations and time-lapse imaging of rodent and human slices of the embryonic cortex, radial glial cells (RGCs) were identified as the primary progenitors or neural stem cells (NSCs) in the developing cortex (Gotz and Huttner, 2005). Simplified, RG in the ventricular zone (VZ) line the ventricular surface and self-renew through symmetric divisions or give rise to basal progenitors (BPs; also called intermediate progenitors) in the subventricular zone (SVZ) that typically divide symmetrically and generate neurons. In contrast to the lissencephalic rodent brain, the developing cortex of gyrated mammals (e.g., humans and ferrets) contains a large number of basal radial glial (bRG) cells that reside in the outer subventricular zone (OSVZ), retain a cellular process that is connected to the pial surface and that are, in contrast to BPs, multipotent, meaning that they have the potency to generate diverse neural cell types (Fietz et al, 2010; Hansen et al, 2010; Reillo et al, 2011).Largely based on the anatomical differences between the developing cortex of lissencephalic and gyrencephalic brains, several hypotheses have been formulated aiming to explain the massive increase in size and induction of brain folding during mammalian evolution. One prominent hypothesis, called the radial unit hypothesis, suggests that the expansion of RGCs lining the ventricle leads to an increase of radial units that generate neurons and thus is responsible for the increase of surface area (Rakic, 1995). Others proposed that the increase in size and folding could be due to an increase in BP expansion in the SVZ compared to RGC numbers in the VZ, a hypothesis called the intermediate progenitor model (Kriegstein et al, 2006). These hypotheses were helpful to start explaining mammalian brain evolution, but testing the exact role of different neural precursors remained extremely challenging due to technical difficulties to selectively manipulating the proliferative activity of distinct precursor populations. Even though previous approaches were successful in enhancing brain size/neuron numbers in mouse models (e.g., by ectopically enhancing WNT signalling activity or manipulating the activity of the small RhoGTPase Cdc42 in neural precursors), these strategies had the drawback that the normal six-layered cortical topography was disrupted, making it difficult to draw definite conclusions (Chenn and Walsh, 2002; Cappello et al, 2006).In a collaborative work from the Calegari and Borrell laboratories, Nonaka-Kinoshita et al, 2013 now used an elegant approach to selectively enhance proliferation of distinct precursor populations in the mouse and ferret developing cortex. They used a previously described approach manipulating cell cycle length and subsequently proliferation by overexpressing the cell cycle regulators cdk4 and cyclinD1 that is sufficient to enhance neurogenesis without affecting cortical layering (a system called 4D) (Lange et al, 2009). For their mouse experiments, Nonaka-Kinoshita et al used a transgenic strategy to transiently overexpress 4D in nestin-expressing precursors using a tetracycline-controlled gene expression system (nestinrtTA/tetbi4D). With this approach, they selectively enhanced proliferation of BPs in the SVZ without affecting the number or proliferation of RGCs in the VZ (Nonaka-Kinoshita et al, 2013). Strikingly, targeted expansion of BPs induced a substantial increase in surface area but was not sufficient to induce cortical folding in the otherwise smooth mouse cortex, challenging the radial unit hypothesis and the intermediate progenitor model with regard to their predictions on the effects on size and/or gyration of the cortex upon expansion of the BP pool. Complementing their findings of BP expansion in the lissencephalic mouse brain, Nonaka-Kinoshita et al used retroviral vectors and electroporation of 4D expression constructs to target 4D expression to neural precursors in the developing ferret cortex that is gyrated under physiological conditions. In the ferret, 4D expression induced proliferation of multipotent bRG located in the OSVZ, as outlined above, a cell type that is found predominantly in gyrated cortices compared to lissencephalic brains. Notably, enhanced proliferation of bRG triggered the formation of novel cortical folds, suggesting that indeed the expansion of bRG may represent a key event during evolution to induce gyration and subsequent surface expansion of the mammalian brain (Borrell and Reillo, 2012; Nonaka-Kinoshita et al, 2013) (Figure 1). This now experimentally supported hypothesis is strongly reinforced by two recent publications: one from (Tuoc et al, 2013) who found that deletion of the chromatin remodelling protein BAF170 increases the BP pool and subsequently enhances brain size; and another one from the Götz laboratory where it was found that experimentally reduced expression levels of the DNA-associated protein Trnp1 substantially increased the expansion of bRG and BPs, inducing folding of the normally lissencephalic mouse brain (Stahl et al, 2013). Taken together, these studies suggest that bRG in the OSVZ play an important role in cortical folding by enhancing the generation of neurons and by providing a glial scaffold for newborn neurons to disperse more laterally and thus to form folds in the developing brain (Reillo et al, 2011).Open in a separate windowFigure 1How different neural precursors appear to regulate size expansion and folding during mammalian brain development. (A) Shown are the main cellular components of the cortex of the lissencephalic mouse brain during embryonic development with RGCs (blue) lining the lateral ventricles in the VZ that generate BPs (yellow) in the SVZ and provide a scaffold for migrating neurons (left; green). Note that the mouse developing brain contains only a few bRG in the OSVZ (red). Notably, expansion of BPs using the 4D strategy developed in the Calegari laboratory increases surface area of the murine cortex without inducing the folding of the smooth mouse brain surface (right panel). (B) In contrast to lissencephalic animals, the developing cortices of species with gyrated brains (e.g., humans and ferrets) contain a substantial number of bRG located in the OSVZ (left panel). 4D-based, virus-mediated expansion of bRG in the ferret cortex leads to the induction of additional folds in the ferret cortex, indicating that the proliferative activity of bRG is critically involved in the extent of folding in physiologically gyrated brains (right panel).Even though this new study challenges previously held concepts regarding size expansion and folding of the mammalian brain, future studies are required that even more selectively enhance the proliferation and expansion of distinct precursor subtypes with high temporal and spatial control. Thus, the combination of sophisticated genetic tools to enhance precursor activity with detailed molecular analyses (e.g., analysing gene expression in highly folded versus unfolded brain regions, an approach that already showed differential levels of Trnp1 expression; Stahl et al, 2013) and live-imaging studies in the developing mammalian cortex will further enhance the understanding how our brains developed during evolution. 相似文献
108.
S.P. Meenakshisundaram B. Karthikeyan K. Muthu S. Sebastian 《Molecular simulation》2013,39(7):584-595
The experimental and theoretical studies on the molecular structure and vibrational spectra of bis(thiourea)zinc(II) chloride (BTZC) crystals were investigated. The Fourier transform infrared, Fourier transform Raman and UV–vis spectra of BTZC were recorded. The molecular geometry and vibrational frequencies of BTZC in the ground state were calculated by using B3LYP with LANL2DZ as basis set. Comparison of the observed structural parameters of BTZC with single-crystal X-ray studies yields a good agreement. Vibrational analysis of the simultaneous IR and Raman activation of the Zn–Cl stretching mode in the molecule provides the evidence for the charge transfer interaction taking place within the molecule. The energy and oscillator strength are calculated by time-dependent density functional theory. The simulated spectra satisfactorily coincide with the experimental spectra. 相似文献
109.
ADP-ribosylation factors (ARFs) are monomeric G proteins that regulate many cellular processes such as reorganization of the actin cytoskeleton. We have previously shown that ARF1 is overexpressed in highly invasive breast cancer cells and contribute to their enhanced migration. In this study, we propose to define the molecular mechanism by which ARF1 regulates this complex cellular response by investigating the role of this ARF GTPase on the activation process of Rac1, a Rho GTPase, associated with lamellipodia formation during cell migration. Here, we first show that inhibition of ARF1 or Rac1 expression markedly impacts the ability of MDA-MB-231 cells to migrate upon EGF stimulation. However, the effect of ARF1 depletion can be reversed by overexpression of the Rac1 active mutant, Rac1 Q61L. Depletion of ARF1 also impairs the ability of EGF stimulation to promote GTP-loading of Rac1. To further investigate the possible cross-talk between ARF1 and Rac1, we next examined whether they could form a complex. We observed that the two GTPases could directly interact independently of the nature of the nucleotide bound to them. EGF treatment however resulted in the association of Rac1 with its effector IRSp53, which was completely abrogated in ARF1 depleted cells. We present evidences that this ARF isoform is responsible for the plasma membrane targeting of both Rac1 and IRSp53, a step essential for lamellipodia formation. In conclusion, this study provides a new mechanism by which ARF1 regulates cell migration and identifies this GTPase as a promising pharmacological target to reduce metastasis formation in breast cancer patients. 相似文献
110.
Spatio-temporal mapping of local soil pH changes induced by roots of lupin and soft-rush 总被引:1,自引:0,他引:1
Nicole Rudolph Sebastian Voss Ahmad B. Moradi Stefan Nagl Sascha E. Oswald 《Plant and Soil》2013,369(1-2):669-680