342 research outputs found
Short but Critical?: How âFake Newsâ and âAnti-Elitistâ Media Attacks Undermine Perceived Message Credibility on Social Media
Citizens increasingly turn to social media for information, where they often rely on cues to judge the credibility of news messages. In these environments, populist politicians use âfake newsâ and âanti-elitistâ attacks to undermine the credibility of news messages. This article argues that to truly understand the impact of these criticism cues, one must simultaneously consider additional contextual cues as well as individual-level moderators. In a factorial survey, we exposed 715 respondents to tweets by a politician retweeting and discrediting a news message of which topic and source varied. We find that both the fake news cue and the anti-elitist cue have limited across-the-board effects but decrease credibility if the message is incongruent with votersâ issue positions. Our results thus offer a more optimistic view on the power of populist media criticism cues and suggest that source and confirmation heuristics are (still) stronger influences on citizensâ credibility evaluations
Entwicklung neuer retroviraler Vektoren fĂŒr die Gentherapie der HIV-Infektion
An den Folgen der HIV-Infektion sind bisher mehr als 15 Millionen Menschen gestorben und die Zahl der Neuinfektionen wĂ€chst stĂ€ndig. Nach EinfĂŒhrung der hochaktiven antiretroviralen Kombinationstherapie (HAART) 1995 konnte die HIV-Replikation im Patienten unterdrĂŒckt und der Verlauf der Krankheit verzögert werden. Aber die Bildung resistenter HIV-StĂ€mme wĂ€hrend der Therapie und die hohe ToxizitĂ€t der Medikamente limitieren diese Erfolge. Einen neuen Therapieansatz bietet die genetische Modifikation von T-Lymphozyten zur "intrazellulĂ€ren Immunisierung" der Zielzellen von HIV. Dabei werden die Zellen mit einem retroviralen Vektor transduziert und exprimieren ein antivirales Gen, das sie vor der HIV-Infektion schĂŒtzt. In Vorarbeiten der Arbeitsgruppe von Laer wurde der retrovirale Vektor M87- Ineo entwickelt, der die Expression des membranverankerten Fusionsinhibitors C36/T20 auf der ZelloberflĂ€che ermöglicht. Durch das Peptid sind die Zielzellen effizient vor der Infektion mit HIV geschĂŒtzt (Hildinger et al., 2001). Das therapeutische Gen von M87-Ineo besteht aus dem Signalpeptid von LNGFR fĂŒr die Translokation in das ER, dem inhibitorischen Peptid C36/T20, das von HIV-1 gp41 abgleitet ist, einem flexiblen Linker sowie aus der TransmembrandomĂ€ne von LNGFR fĂŒr die Verankerung in der Plasmamembran. In der vorliegenden Arbeit wurde dieser retrovirale Vektor erfolgreich fĂŒr die klinische Applikation zur Gentherapie der HIV-Infektion optimiert. Ziel war es, die potentielle ImmunogenitĂ€t des exprimierten Peptides zu minimieren, die Expression zu erhöhen sowie der Resistenzbildung entgegenzuwirken. Der Linker im Basiskonstrukt M87-Ineo ist abgeleitet aus dem Gelenk des murinen Antikörpers von IgG2 und verleiht dem Hemmpeptid FlexibilitĂ€t. Um die potentielle ImmunogenitĂ€t des exprimierten Peptides zu reduzieren, wurde der Linker des murinen Antikörpers IgG2 durch Gelenke ("Hinge") von humanen Antikörpern der IgG-Klasse ersetzt. Das Konstrukt mit der humanen "Hinge" von IgG2 exprimierte genauso hoch wie das Basiskonstrukt und hemmte mindestens so effizient die HIV-Replikation. Durch die N-terminale VerlĂ€ngerung des C-Peptids um 10 AminosĂ€uren konnte das Risiko der Resistenzbildung minimiert werden. Das verlĂ€ngerte C-Peptid war in der Lage, HIV-HĂŒllproteine zu hemmen, die gegen das C36/T20-Peptid resistent sind. Das optimierte Peptid von M87o bestand somit aus dem Membrananker von trunkiertem CD34, dem Linker von humanem IgG2 sowie aus dem verlĂ€ngerten C-Peptid (C46). Weiterhin wurde ohne Verlust der Expression oder Hemmwirkung des membranverankerten C-Peptids ein RNAElement (RRE decoy) erfolgreich als weiteres Hemmprinzip in den Vektor eingefĂŒgt, um die Bildung resistenter HIV-StĂ€mme zu unterbinden. Durch Einsatz eines optimierten Leaderelementes im retroviralen Vektor konnte die Expression des inhibitorischen Peptides mehr als verzehnfacht werden. Damit konnte das Peptid und dessen Hemmung erstmals auch in primĂ€ren Zellen nachgewiesen werden. Der Vergleich zwischen dem Basiskonstrukt M87-Ineo und dem optimierten Konstrukt M87o-RRE-Ineo zeigte, dass die erhöhte Expression auch mit einer wesentlich verbesserten Hemmwirkung einherging. In Zell-Zellfusionsassays wurde auĂerdem nachgewiesen, dass die Wirkung des C-Peptids auf der Hemmung des Viruseintritts von HIV in die Zelle beruht. FĂŒr die klinische Applikation wurde der Vektor M87o-RRE konstruiert, der die optimalen Vektorelemente und Peptidmodule enthielt, aber aus dem das Neomycin-Resistenzgen entfernt wurde. Dies fĂŒhrte zu einer nochmals höheren Expression des C-Peptids sowie zur weiteren Verminderung der ImmunogenitĂ€t des retroviralen Vektors. Das Markergen wurde ohnehin nicht mehr benötigt, da die genetisch modifizierten Zellen aufgrund der hohen Transgenexpression einfach detektiert werden konnten. Der optimierte Vektor M87o-RRE hemmte die HIV-Replikation so effizient, dass bisher keine resistenten StĂ€mme isoliert werden konnten. Bei ToxizitĂ€tsstudien in Maus und Rhesusmacaquen konnten keine Nebenwirkungen oder ImmunogenitĂ€t beobachtet werden. Durch die erfolgreiche Optimierung steht nun fĂŒr die klinische Studie der Phase I der bestmögliche retrovirale Vektor zur VerfĂŒgung
How Politiciansâ Attacks on Science Communication Influence Public Perceptions of Journalists and Scientists
In todayâs âpost-truthâ world, concerns over political attacks on the legitimacy of expert knowledge and scientific facts are growing. Especially populist politicians frequently use their social media platforms to target science and journalism, arguing these are part of an âevil elite,â deliberately misleading the public by spreading disinformation. While this type of discourse is highly concerning, thus far, we lack empirical evidence on how these accusations affect the public perceptions of scientists and journalists. To fill this gap, this study tests how politiciansâ attacks affect citizensâ trust in journalists and scientists and the information provided by them. Furthermore, it investigates whether this discourse renders hostility towards journalists and scientists acceptable and whether there are effects on the image of politicians using such anti-science rhetoric. Findings suggest that the effects of politiciansâ attacks on citizensâ perceptions of scientists and journalists are limited. Only individuals with strong anti-elitist attitudes are susceptible to disinformation accusations and indicate less belief in discredited scientific information. Interestingly, these individuals also perceive politicians using such attacks as more trustworthy and authentic
ProMEX â a mass spectral reference database for plant proteomics
The ProMEX database is one of the main collection of annotated tryptic peptides in plant proteomics. The main objective of the ProMEX database is to provide experimental MS/MS-based information for cell type-specific or sub-cellular proteomes in Arabidopsis thaliana, Medicago truncatula, Chlamydomonas reinhardtii, Lotus japonicus, Lotus corniculatus, Phaseolus vulgaris, Lycopersicon esculentum, Solanum tuberosum, Nicotiana tabacum, Glycine max, Zea mays, Bradyrhizobium japonicum, and Sinorhizobium meliloti. Direct links at the protein level to the most relevant databases are present in ProMEX. Furthermore, the spectral sequence information are linked to their respective pathways and can be viewed in pathway maps
Caenorhabditis elegans chromosome arms are anchored to the nuclear membrane via discontinuous association with LEM-2
Abstract Background Although Caenorhabditis elegans was the first multicellular organism with a completely sequenced genome, how this genome is arranged within the nucleus is not known. Results We determined the genomic regions associated with the nuclear transmembrane protein LEM-2 in mixed-stage C. elegans embryos via chromatin immunoprecipitation. Large regions of several megabases on the arms of each autosome were associated with LEM-2. The center of each autosome was mostly free of such interactions, suggesting that they are largely looped out from the nuclear membrane. Only the left end of the X chromosome was associated with the nuclear membrane. At a finer scale, the large membrane-associated domains consisted of smaller subdomains of LEM-2 associations. These subdomains were characterized by high repeat density, low gene density, high levels of H3K27 trimethylation, and silent genes. The subdomains were punctuated by gaps harboring highly active genes. A chromosome arm translocated to a chromosome center retained its association with LEM-2, although there was a slight decrease in association near the fusion point. Conclusions Local DNA or chromatin properties are the main determinant of interaction with the nuclear membrane, with position along the chromosome making a minor contribution. Genes in small gaps between LEM-2 associated regions tend to be highly expressed, suggesting that these small gaps are especially amenable to highly efficient transcription. Although our data are derived from an amalgamation of cell types in mixed-stage embryos, the results suggest a model for the spatial arrangement of C. elegans chromosomes within the nucleus
Repression of Germline Genes in \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e Somatic Tissues by H3K9 Dimethylation of Their Promoters
Repression of germline-promoting genes in somatic cells is critical for somatic development and function. To study how germline genes are repressed in somatic tissues, we analyzed key histone modifications in three Caenorhabditis elegans synMuv B mutants, lin-15B, lin-35, and lin-37âall of which display ectopic expression of germline genes in the soma. LIN-35 and LIN-37 are members of the conserved DREAM complex. LIN-15B has been proposed to work with the DREAM complex but has not been shown biochemically to be a member of the complex. We found that, in wild-type worms, synMuv B target genes and germline genes are enriched for the repressive histone modification dimethylation of histone H3 on lysine 9 (H3K9me2) at their promoters. Genes with H3K9me2 promoter localization are evenly distributed across the autosomes, not biased toward autosomal arms, as are the broad H3K9me2 domains. Both synMuv B targets and germline genes display a dramatic reduction of H3K9me2 promoter localization in lin-15B mutants, but much weaker reduction in lin-35 and lin-37mutants. This difference between lin-15B and DREAM complex mutants likely represents a difference in molecular function for these synMuv B proteins. In support of the pivotal role of H3K9me2 in regulation of germline genes by LIN-15B, global loss of H3K9me2 but not H3K9me3 results in phenotypes similar to synMuv B mutants, high-temperature larval arrest, and ectopic expression of germline genes in the soma. We propose that LIN-15B-driven enrichment of H3K9me2 at promoters of germline genes contributes to repression of those genes in somatic tissues
The Septins Function in G1 Pathways that Influence the Pattern of Cell Growth in Budding Yeast
The septins are a conserved family of proteins that have been proposed to carry out diverse functions. In budding yeast, the septins become localized to the site of bud emergence in G1 but have not been thought to carry out important functions at this stage of the cell cycle. We show here that the septins function in redundant mechanisms that are required for formation of the bud neck and for the normal pattern of cell growth early in the cell cycle. The Shs1 septin shows strong genetic interactions with G1 cyclins and is directly phosphorylated by G1 cyclin-dependent kinases, consistent with a role in early cell cycle events. However, Shs1 phosphorylation site mutants do not show genetic interactions with the G1 cyclins or obvious defects early in the cell cycle. Rather, they cause an increased cell size and aberrant cell morphology that are dependent upon inhibitory phosphorylation of Cdk1 at the G2/M transition. Shs1 phosphorylation mutants also show defects in interaction with the Gin4 kinase, which associates with the septins during G2/M and plays a role in regulating inhibitory phosphorylation of Cdk1. Phosphorylation of Shs1 by G1 cyclin-dependent kinases plays a role in events that influence Cdk1 inhibitory phosphorylation
Identification of proteins from Mycobacterium tuberculosis missing in attenuated Mycobacterium bovis BCG strains.
A proteome approach, combining high-resolution two-dimensional electrophoresis (2-DE) with mass spectrometry, was used to compare the cellular protein composition of two virulent strains of Mycobacterium tuberculosis with two attenuated strains of Mycobacterium bovis Bacillus Calmette-Guerin (BCG), in order to identify unique proteins of these strains. Emphasis was given to the identification of M. tuberculosis specific proteins, because we consider these proteins to represent putative virulence factors and interesting candidates for vaccination and diagnosis of tuberculosis. The genome of M. tuberculosis strain H37Rv comprises nearly 4000 predicted open reading frames. In contrast, the separation of proteins from whole mycobacterial cells by 2-DE resulted in silver-stained patterns comprising about 1800 distinct protein spots. Amongst these, 96 spots were exclusively detected either in the virulent (56 spots) or in the attenuated (40 spots) mycobacterial strains. Fifty-three of these spots were analyzed by mass spectrometry, of which 41 were identified, including 32 M. tuberculosis specific spots. Twelve M. tuberculosis specific spots were identified as proteins, encoded by genes previously reported to be deleted in M. bovis BCG. The remaining 20 spots unique for M. tuberculosis were identified as proteins encoded by genes that are not known to be missing in M. bovis BCG
Caenorhabditis elegans chromosome arms are anchored to the nuclear membrane via discontinuous association with LEM-2
Abstract Background Although Caenorhabditis elegans was the first multicellular organism with a completely sequenced genome, how this genome is arranged within the nucleus is not known. Results We determined the genomic regions associated with the nuclear transmembrane protein LEM-2 in mixed-stage C. elegans embryos via chromatin immunoprecipitation. Large regions of several megabases on the arms of each autosome were associated with LEM-2. The center of each autosome was mostly free of such interactions, suggesting that they are largely looped out from the nuclear membrane. Only the left end of the X chromosome was associated with the nuclear membrane. At a finer scale, the large membrane-associated domains consisted of smaller subdomains of LEM-2 associations. These subdomains were characterized by high repeat density, low gene density, high levels of H3K27 trimethylation, and silent genes. The subdomains were punctuated by gaps harboring highly active genes. A chromosome arm translocated to a chromosome center retained its association with LEM-2, although there was a slight decrease in association near the fusion point. Conclusions Local DNA or chromatin properties are the main determinant of interaction with the nuclear membrane, with position along the chromosome making a minor contribution. Genes in small gaps between LEM-2 associated regions tend to be highly expressed, suggesting that these small gaps are especially amenable to highly efficient transcription. Although our data are derived from an amalgamation of cell types in mixed-stage embryos, the results suggest a model for the spatial arrangement of C. elegans chromosomes within the nucleus
The Histone H3K36 Methyltransferase MES-4 Acts Epigenetically to Transmit the Memory of Germline Gene Expression to Progeny
Methylation of histone H3K36 in higher eukaryotes is mediated by multiple methyltransferases. Set2-related H3K36 methyltransferases are targeted to genes by association with RNA Polymerase II and are involved in preventing aberrant transcription initiation within the body of genes. The targeting and roles of the NSD family of mammalian H3K36 methyltransferases, known to be involved in human developmental disorders and oncogenesis, are not known. We used genome-wide chromatin immunoprecipitation (ChIP) to investigate the targeting and roles of the Caenorhabditis elegans NSD homolog MES-4, which is maternally provided to progeny and is required for the survival of nascent germ cells. ChIP analysis in early C. elegans embryos revealed that, consistent with immunostaining results, MES-4 binding sites are concentrated on the autosomes and the leftmost âŒ2% (300 kb) of the X chromosome. MES-4 overlies the coding regions of approximately 5,000 genes, with a modest elevation in the 5âČ regions of gene bodies. Although MES-4 is generally found over Pol II-bound genes, analysis of gene sets with different temporal-spatial patterns of expression revealed that Pol II association with genes is neither necessary nor sufficient to recruit MES-4. In early embryos, MES-4 associates with genes that were previously expressed in the maternal germ line, an interaction that does not require continued association of Pol II with those loci. Conversely, Pol II association with genes newly expressed in embryos does not lead to recruitment of MES-4 to those genes. These and other findings suggest that MES-4, and perhaps the related mammalian NSD proteins, provide an epigenetic function for H3K36 methylation that is novel and likely to be unrelated to ongoing transcription. We propose that MES-4 transmits the memory of gene expression in the parental germ line to offspring and that this memory role is critical for the PGCs to execute a proper germline program
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