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C2-symmetric bisamidines : chiral Brønsted bases catalysing the Diels-Alder reaction of anthrones
(2008)
C2-symmetric bisamidines 8 have been tested as chiral Brønsted bases in the Diels- Alder reaction of anthrones and N-substituted maleimides. High yields of cycloadducts and significant asymmetric inductions up to 76% ee are accessible. The proposed mechanism involves proton transfer between anthrone and bisamidine, association of the resulting ions and finally a cycloaddition step stereoselectively controlled by the chiral ion pair.
Oscillatory activity in human electro- or magnetoencephalogram has been related to cortical stimulus representations and their modulation by cognitive processes. Whereas previous work has focused on gamma-band activity (GBA) during attention or maintenance of representations, there is little evidence for GBA reflecting individual stimulus representations. The present study aimed at identifying stimulus-specific GBA components during auditory spatial short-term memory. A total of 28 adults were assigned to 1 of 2 groups who were presented with only right- or left-lateralized sounds, respectively. In each group, 2 sample stimuli were used which differed in their lateralization angles (15° or 45°) with respect to the midsagittal plane. Statistical probability mapping served to identify spectral amplitude differences between 15° versus 45° stimuli. Distinct GBA components were found for each sample stimulus in different sensors over parieto-occipital cortex contralateral to the side of stimulation peaking during the middle 200–300 ms of the delay phase. The differentiation between "preferred" and "nonpreferred" stimuli during the final 100 ms of the delay phase correlated with task performance. These findings suggest that the observed GBA components reflect the activity of distinct networks tuned to spatial sound features which contribute to the maintenance of task-relevant information in short-term memory.
Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms.
The degradation of the poly(A) tail is crucial for posttranscriptional gene regulation and for quality control of mRNA. Poly(A)-specific ribonuclease (PARN) is one of the major mammalian 3’ specific exo-ribonucleases involved in the degradation of the mRNA poly(A) tail, and it is also involved in the regulation of translation in early embryonic development. The interaction between PARN and the m7GpppG cap of mRNA plays a key role in stimulating the rate of deadenylation. Here we report the solution structures of the cap-binding domain of mouse PARN with and without the m7GpppG cap analog. The structure of the cap-binding domain adopts the RNA recognition motif (RRM) with a characteristic a-helical extension at its C-terminus, which covers the b-sheet surface (hereafter referred to as PARN RRM). In the complex structure of PARN RRM with the cap analog, the base of the N7-methyl guanosine (m7G) of the cap analog stacks with the solvent-exposed aromatic side chain of the distinctive tryptophan residue 468, located at the C-terminal end of the second b-strand. These unique structural features in PARN RRM reveal a novel cap-binding mode, which is distinct from the nucleotide recognition mode of the canonical RRM domains.
We performed a bioinformatical analysis of protein export elements (PEXEL) in the putative proteome of the malaria parasite Plasmodium falciparum. A protein family-specific conservation of physicochemical residue profiles was found for PEXEL-flanking sequence regions. We demonstrate that the family members can be clustered based on the flanking regions only and display characteristic hydrophobicity patterns. This raises the possibility that the flanking regions may contain additional information for a family-specific role of PEXEL. We further show that signal peptide cleavage results in a positional alignment of PEXEL from both proteins with, and without, a signal peptide.
While the adaptor SKAP-55 mediates LFA-1 adhesion on T-cells, it is not known whether the adaptor regulates other aspects of signaling. SKAP-55 could potentially act as a node to coordinate the modulation of adhesion with downstream signaling. In this regard, the GTPase p21ras and the extracellular signal-regulated kinase (ERK) pathway play central roles in T-cell function. In this study, we report that SKAP-55 has opposing effects on adhesion and the activation of the p21ras -ERK pathway in T-cells. SKAP-55 deficient primary T-cells showed a defect in LFA-1 adhesion concurrent with the hyper-activation of the ERK pathway relative to wild-type cells. RNAi knock down (KD) of SKAP-55 in T-cell lines also showed an increase in p21ras activation, while over-expression of SKAP-55 inhibited activation of ERK and its transcriptional target ELK. Three observations implicated the p21ras activating exchange factor RasGRP1 in the process. Firstly, SKAP-55 bound to RasGRP1 via its C-terminus, while secondly, the loss of binding abrogated SKAP-55 inhibition of ERK and ELK activation. Thirdly, SKAP-55−/− primary T-cells showed an increased presence of RasGRP1 in the trans-Golgi network (TGN) following TCR activation, the site where p21ras becomes activated. Our findings indicate that SKAP-55 has a dual role in regulating p21ras-ERK pathway via RasGRP1, as a possible mechanism to restrict activation during T-cell adhesion.
Diabrotica virgifera virgifera LeConte, in its original North American habitat also known as western corn rootworm beetle, actively continues its expansion to new territories and uses Homo sapiens as its prime vector. It took only 15 years to spread to and occupy the southeastern and central parts of Europe, so far with the exception of Denmark where it has not been documented as of 2007. Economic thresholds have been reached and surpassed only in Southeast European countries like Slovakia, Hungary, Serbia, Eastern Croatia, Romania and Northern Italy. But both, the area affected and the severity of symptoms are increasing. Model calculations by a number of authors (Baufeld & Enzian, 2005 a and b; Hongmei Li & al. 2006, CLIMEX model) indicate a definitive propensity of D. v. virgifera to expand its currently occupied territory to regions with moderate temperatures and Zea mays cultivation. East Africa and Eastern Asia are included in the list of potential candidates for future inadvertent introduction. In most discussions it is tacitly and erroneously assumed that Z. mays is the only or the only important host of D. v. virgifera. Our recent observations in Eastern Slovenia on the oil pumpkin Cucurbita pepo indicate, however, that this simplifying assumption is notlonger strictly valid. It has to be modified in light of new evidence. Here, we report a few field experiments conducted in August of 2006 clarifying the host status of C. pepo in a European country.
Der inzwischen auf der EPPO A1-Liste aufgeführte Quarantäneschädling, der Bockkäfer Anoplophora glabripennis (Motschulsky, 1853), ist seit seiner Einschleppung nach Braunau am Inn (Österreich) im Jahr 2001 in ganz Europa ein Begriff. Neben zwei unabhängigen Fundorten in Frankreich, 2003 in Gien und 2004 in Sainte-Anne-sur-Brivet (Hérard & al. 2005) wurde eine Freiland-Population dieser Laubbäume schädigenden Art erstmals 2004 auch in Deutschland festgestellt. Bisherige Funde von Käfern in Deutschland waren auf das Gelände des Hamburger Hafens, Umschlagplatz vieler Container aus dem asiatischen Raum, beschränkt (Schliesske 2001). Es konnte aber nie eine Übersiedelung auf Laubbäume in der Umgebung beobachtet werden. Die Situation änderte sich gravierend, als offensichtlich befallene Bäume in Neukirchen am Inn (Gemeinde Neuburg am Inn, Landkreis Passau) in Bayern festgestellt wurden. Symptome wie mangelnde Belaubung, kraterförmige Eiablagestellen und Austritt von Bohrmehl an einem Ahornbaum deuteten auf Befall mit A. glabripennis hin. Nach Entnahme von Astteilen wurden in Gängen Bockkäfer-Larven gefunden, die von Kollegen des Bundesamtes und Forschungszentrums für Wald (BFW) in Wien mittels DNA-Analyse zweifelsfrei als A. glabripennis identifiziert wurden (Hoyer & al. 2003).
The codling moth, Cydia pomonella (Lep., Tortricidae), is a significant pest of orchard crops such as apple and pear in Southern Germany, and can cause severe economic damage to apple crops. Due to resistance to conventional pesticides and the growing market for organic fruit, Cydia pomonella Granulovirus (CpGV) has been used to control C. pomonella in Germany for over 10 years. Recently, populations exhibiting resistance to CpGV have been reported. In this study, we have used amplified fragment length polymorphism (AFLP) markers to estimate genetic variations between eight different C. pomonella populations, which were obtained from different locations exhibiting varying levels of resistance to CpGV. Three different AFLP primer combinations generated a total of 194 AFLP fragments, ranging from 57.84 to 424.11 bp, with an average of 59.23 amplified fragments per primer combination. The total number of segregating fragments ranged from 181 to 115 and resulted in a high loci polymorphism of 100% in most cases, except for two populations, where it was found to be 88.1% and 93.3%. An analysis of genetic variation based on the obtained AFLP markers resulted in high gene diversity (Hj) values, ranging between 0.2884 to 0.3508. Hj values also indicated a loss in gene diversity within a population over time. The Wright Fixation Index (FST) values indicated a low to moderate genetic differentiation in the populations. The cluster analysis (UPGMA), based on genetic distance values, showed that the majority of C. pomonella populations from different locations were clearly distributed into distinct groups and showed a large genetic variability.