285 research outputs found
An integral boundary layer equation for film flow over inclined wavy bottoms
We study the flow of an incompressible liquid film down a wavy incline.
Applying a Galerkin method with only one ansatz function to the Navier-Stokes
equations we derive a second order weighted residual integral boundary layer
equation, which in particular may be used to describe eddies in the troughs of
the wavy bottom. We present numerical results which show that our model is
qualitatively and quantitatively accurate in wide ranges of parameters, and we
use the model to study some new phenomena, for instance the occurrence of a
short wave instability for laminar flows which does not exist over flat bottom.Comment: 23 pages, 12 figures. We added a new Section "Regularization" in
which we additionally apply a Pade-like regularization to the weighted
residual integral boundary layer equatio
Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment
Selective expression of murine cytomegalovirus (MCMV) immediate-early (IE) genes leads to
the presentation by the major histocompatibility complex (MHC) class I molecule L a of a
peptide derived from MCMV IE protein pp89 (Reddehase, M. J., J. B. Rothbard, and U. H.
Koszinowski. 1989. Nature (Lond.). 337:651). Characterization of endogenous antigenic peptides
identified the pp89 peptide as the nonapeptide msYPHFMFFNLt76 (del Val, M., H.-J. Schlicht,
T. Ruppert, M. J. Reddehase, and U. H. Koszinowski. 1991. Cell. 66:1145). Subsequent expression
of MCMV early genes prevents presentation of pp89 (del Val, M., K. Mfinch, M. J. Reddehase,
and U. H. Koszinowski. 1989. Cell. 58:305). We report on the mechanism by which MCMV
early genes interfere with antigen presentation. Expression of the IE promoter-driven bacterial
gene lacZ by recombinant MCMV subjected antigen presentation of B-galactosidase to the same
control and excluded antigen specificity. The La-dependent presence of naturally processed
antigenic peptides also in nonpresenting cells located the inhibitory function subsequent to the
step of antigen processing. The finding that during the E phase of MCMV gene expression the
MHC class I heavy chain glycosylation remained in an Endo H-sensitive form suggested a block
within the endoplasmic reticulum/c/s-Golgi compartment. The failure to present antigenic peptides
was explained by a general retention of nascent assembled trimolecular MHC class I complexes.
Accordingly, at later stages of infection a significant decrease of surface MHC class I expression
was seen, whereas other membrane glycoproteins remained unaffected. Thus, MCMV E genes
endow this virus with an effective immune evasion potential. These results also indicate that
the formation of the trimolecular complex of MHC dass I heavy chain, ~2-microglobulin, and
the finally trimmed peptide is completed before entering the medial-Golgi compartment
The portfolio approach - rediscovering the learning subject? Reception and developments within the German speaking countries
Das Portfolio im Bildungsbereich avanciert im deutschen Sprachraum gegenwärtig zu einem viel gebrauchten Schlagwort. Mit der Häufigkeit seiner Verwendung steigt aber nicht automatisch die Klarheit über die dahinter stehenden Konzepte und Vorstellungen von Bildung, Lernen und Unterricht. Der Portfolioansatz ist ein anspruchvolles und voraussetzungsreiches Konzept, bei dessen Einführung zahlreiche äußere wie innere Voraussetzungen beachtet werden müssen. (DIPF/Orig.)At present, the term "Portfolio" is being used in many different meanings. Its frequent use does not clarify the underlying concepts and ideas of education, learning and teaching. The use of Portfolio in education is demanding. It requires many preconditions and qualifications which should receive more attention before introducing it into classroom work. (DIPF/Orig.
Spin dynamics in copper metaborate studied by muon spin relaxation
Copper metaborate CuBO was studied by muon spin relaxation
measurements in order to clarify its static and dynamic magnetic properties.
The time spectra of muon spin depolarization suggest that the local fields at
the muon site contain both static and fluctuating components in all ordered
phases down to 0.3 K. In the weak ferromagnetic phase (20 K~~9.3 K), the
static component is dominant. On the other hand, upon cooling the fluctuating
component becomes dominant in the incommensurate helix phase (9.3K > T > 1.4K).
The dynamical fluctuations of the local fields persist down to 0.3K, where a
new incommensurate phase (T < 1.4K) is expected to appear. This result suggests
that spins fluctuate even at T \to 0. We propose two possible origins of the
remnant dynamical spin fluctuations: frustration of the exchange interactions
and the dynamic behavior of the soliton lattice
NleC, a Type III Secretion Protease, Compromises NF-κB Activation by Targeting p65/RelA
The NF-κB signaling pathway is central to the innate and adaptive immune responses. Upon their detection of pathogen-associated molecular patterns, Toll-like receptors on the cell surface initiate signal transduction and activate the NF-κB pathway, leading to the production of a wide array of inflammatory cytokines, in attempt to eradicate the invaders. As a countermeasure, pathogens have evolved ways to subvert and manipulate this system to their advantage. Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) are closely related bacteria responsible for major food-borne diseases worldwide. Via a needle-like protein complex called the type three secretion system (T3SS), these pathogens deliver virulence factors directly to host cells and modify cellular functions, including by suppressing the inflammatory response. Using gain- and loss-of-function screenings, we identified two bacterial effectors, NleC and NleE, that down-regulate the NF-κB signal upon being injected into a host cell via the T3SS. A recent report showed that NleE inhibits NF-κB activation, although an NleE-deficient pathogen was still immune-suppressive, indicating that other anti-inflammatory effectors are involved. In agreement, our present results showed that NleC was also required to inhibit inflammation. We found that NleC is a zinc protease that disrupts NF-κB activation by the direct cleavage of NF-κB's p65 subunit in the cytoplasm, thereby decreasing the available p65 and reducing the total nuclear entry of active p65. More importantly, we showed that a mutant EPEC/EHEC lacking both NleC and NleE (ΔnleC ΔnleE) caused greater inflammatory response than bacteria carrying ΔnleC or ΔnleE alone. This effect was similar to that of a T3SS-defective mutant. In conclusion, we found that NleC is an anti-inflammatory bacterial zinc protease, and that the cooperative function of NleE and NleC disrupts the NF-κB pathway and accounts for most of the immune suppression caused by EHEC/EPEC
Leukocyte Attraction by CCL20 and Its Receptor CCR6 in Humans and Mice with Pneumococcal Meningitis
We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6 deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment
Functional Interaction between Type III-Secreted Protein IncA of Chlamydophila psittaci and Human G3BP1
Chlamydophila (Cp.) psittaci, the causative agent of psittacosis in birds and humans, is the most important zoonotic pathogen of the family Chlamydiaceae. These obligate intracellular bacteria are distinguished by a unique biphasic developmental cycle, which includes proliferation in a membrane-bound compartment termed inclusion. All Chlamydiaceae spp. possess a coding capacity for core components of a Type III secretion apparatus, which mediates specific delivery of anti-host effector proteins either into the chlamydial inclusion membrane or into the cytoplasm of target eukaryotic cells. Here we describe the interaction between Type III-secreted protein IncA of Cp. psittaci and host protein G3BP1 in a yeast two-hybrid system. In GST-pull down and co-immunoprecipitation experiments both in vitro and in vivo interaction between full-length IncA and G3BP1 were shown. Using fluorescence microscopy, the localization of G3BP1 near the inclusion membrane of Cp. psittaci-infected Hep-2 cells was demonstrated. Notably, infection of Hep-2 cells with Cp. psittaci and overexpression of IncA in HEK293 cells led to a decrease in c-Myc protein concentration. This effect could be ascribed to the interaction between IncA and G3BP1 since overexpression of an IncA mutant construct disabled to interact with G3BP1 failed to reduce c-Myc concentration. We hypothesize that lowering the host cell c-Myc protein concentration may be part of a strategy employed by Cp. psittaci to avoid apoptosis and scale down host cell proliferation
IL-17A/F-Signaling Does Not Contribute to the Initial Phase of Mucosal Inflammation Triggered by S. Typhimurium
Salmonella enterica subspecies 1 serovar Typhimurium (S. Typhimurium) causes diarrhea and acute inflammation of the intestinal mucosa. The pro-inflammatory cytokines IL-17A and IL-17F are strongly induced in the infected mucosa but their contribution in driving the tissue inflammation is not understood. We have used the streptomycin mouse model to analyze the role of IL-17A and IL-17F and their cognate receptor IL-17RA in S. Typhimurium enterocolitis. Neutralization of IL-17A and IL-17F did not affect mucosal inflammation triggered by infection or spread of S. Typhimurium to systemic sites by 48 h p.i. Similarly, Il17ra−/− mice did not display any reduction in infection or inflammation by 12 h p.i. The same results were obtained using S. Typhimurium variants infecting via the TTSS1 type III secretion system, the TTSS1 effector SipA or the TTSS1 effector SopE. Moreover, the expression pattern of 45 genes encoding chemokines/cytokines (including CXCL1, CXCL2, IL-17A, IL-17F, IL-1α, IL-1β, IFNγ, CXCL-10, CXCL-9, IL-6, CCL3, CCL4) and antibacterial molecules was not affected by Il17ra deficiency by 12 h p.i. Thus, in spite of the strong increase in Il17a/Il17f mRNA in the infected mucosa, IL-17RA signaling seems to be dispensable for eliciting the acute disease. Future work will have to address whether this is attributable to redundancy in the cytokine signaling network
Regulation of Toll-like receptor signaling by NDP52-mediated selective autophagy is normally inactivated by A20
Toll-like receptor (TLR) signaling is linked to autophagy that facilitates elimination of intracellular pathogens. However, it is largely unknown whether autophagy controls TLR signaling. Here, we report that poly(I:C) stimulation induces selective autophagic degradation of the TLR adaptor molecule TRIF and the signaling molecule TRAF6, which is revealed by gene silencing of the ubiquitin-editing enzyme A20. This type of autophagy induced formation of autophagosomes and could be suppressed by an autophagy inhibitor and lysosomal inhibitors. However, this autophagy was not associated with canonical autophagic processes, including involvement of Beclin-1 and conversion of LC3-I to LC3-II. Through screening of TRIF-interacting ‘autophagy receptors’ in human cells, we identified that NDP52 mediated the selective autophagic degradation of TRIF and TRAF6 but not TRAF3. NDP52 was polyubiquitinated by TRAF6 and was involved in aggregation of TRAF6, which may result in the selective degradation. Intriguingly, only under the condition of A20 silencing, NDP52 could effectively suppress poly(I:C)-induced proinflammatory gene expression. Thus, this study clarifies a selective autophagic mechanism mediated by NDP52 that works downstream of TRIF–TRAF6. Furthermore, although A20 is known as a signaling fine-tuner to prevent excess TLR signaling, it paradoxically downregulates the fine-tuning effect of NDP52 on TLR signaling
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