Porphyromonas gingivalis fimbrial protein Mfa5 contains a von Willebrand factor domain and an intramolecular isopeptide

The Gram-negative bacterium Porphyromonas gingivalis is a secondary colonizer of the oral biofilm and is involved in the onset and progression of periodontitis. Its fimbriae, of type-V, are important for attachment to other microorganisms in the biofilm and for adhesion to host cells. The fimbriae are assembled from five proteins encoded by the mfa1 operon, of which Mfa5 is one of the ancillary tip proteins. Here we report the X-ray structure of the N-terminal half of Mfa5, which reveals a von Willebrand factor domain and two IgG-like domains. One of the IgG-like domains is stabilized by an intramolecular isopeptide bond, which is the first such bond observed in a Gram-negative bacterium. These features make Mfa5 structurally more related to streptococcal adhesins than to the other P. gingivalis Mfa proteins. The structure reported here indicates that horizontal gene transfer has occurred among the bacteria within the oral biofilm

Structure of Shigella IpgB2 in Complex with Human RhoA: IMPLICATIONS FOR THE MECHANISM OF BACTERIAL GUANINE NUCLEOTIDE EXCHANGE FACTOR MIMICRY*

A common theme in bacterial pathogenesis is the manipulation of eukaryotic cells by targeting the cytoskeleton. This is in most cases achieved either by modifying actin, or indirectly via activation of key regulators controlling actin dynamics such as Rho-GTPases. A novel group of bacterial virulence factors termed the WXXXE family has emerged as guanine nucleotide exchange factors (GEFs) for these GTPases. The precise mechanism of nucleotide exchange, however, has remained unclear. Here we report the structure of the WXXXE-protein IpgB2 from Shigella flexneri and its complex with human RhoA. We unambiguously identify IpgB2 as a bacterial RhoA-GEF and dissect the molecular mechanism of GDP release, an essential prerequisite for GTP binding. Our observations uncover that IpgB2 induces conformational changes on RhoA mimicking DbI- but not DOCK family GEFs. We also show that dissociation of the GDP·Mg2+ complex is preceded by the displacement of the metal ion to the α-phosphate of the nucleotide, diminishing its affinity to the GTPase. These data refine our understanding of the mode of action not only of WXXXE GEFs but also of mammalian GEFs of the DH/PH family

Anpassningens dilemman. En studie om svensklärares resonemang kring anpassningar i litteraturundervisningen

Syftet med undersökningen är att undersöka hur svensklärare resonerar kring anpassningar för elever i svårigheter och för elever i behov av mer utmanande uppgifter i litteraturundervisningen, samt vilka metoder lärarna använder i deras anpassningar. Genom att utgå från ett relationellt specialpedagogiskt perspektiv samt Judith Langers litteraturreceptionsteori har fem intervjuer med svensklärare på gymnasieskolan genomförts. Intervjuerna har efter transkriberingen tematiserats för att sortera informanternas svar i kategorier. Analysen resulterade i kategorierna: motivation, individanpassning, tid, fördjupning, bredd, metod och attityd. Lärarnas svar visar att elever i svårigheter behöver motiveras i större utsträckning än andra elevgrupper, samt att en individanpassning behöver ske för dem. När lärarna resonerar kring de elever som behöver mer utmanande uppgifter visar resultatet att lärarna inte har samma möjlighet att anpassa undervisningen för dem som för elever i svårigheter. Det menar lärarna beror på tidsbrist och att det saknas strategier för att möta den elevgruppen. De anpassningar som nämns för elever i behov av mer utmanande uppgifter är fler eller fördjupande uppgifter inom samma ämne. Lärarna utgår i första hand från ett kategoriskt perspektiv i sin analys av vem som är bäraren av de pedagogiska problemen. Resultatet visar att det finns utrymme att arbeta med elevernas föreställningsvärldar för att anpassa undervisningen för samtliga elevgrupper i undervisningen

Impaired complex I repair causes recessive Leber's hereditary optic neuropathy

Leber?s hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was the first to be genetically defined by a point mutation in mitochondrial DNA (mtDNA). A molecular diagnosis is achieved in up to 95% of cases, the vast majority of which are accounted for by 3 mutations within mitochondrial complex I subunit?encoding genes in the mtDNA (mtLHON). Here, we resolve the enigma of LHON in the absence of pathogenic mtDNA mutations. We describe biallelic mutations in a nuclear encoded gene, DNAJC30, in 33 unsolved patients from 29 families and establish an autosomal recessive mode of inheritance for LHON (arLHON), which to date has been a prime example of a maternally inherited disorder. Remarkably, all hallmarks of mtLHON were recapitulated, including incomplete penetrance, male predominance, and significant idebenone responsivity. Moreover, by tracking protein turnover in patient-derived cell lines and a DNAJC30-knockout cellular model, we measured reduced turnover of specific complex I N-module subunits and a resultant impairment of complex I function. These results demonstrate that DNAJC30 is a chaperone protein needed for the efficient exchange of complex I subunits exposed to reactive oxygen species and integral to a mitochondrial complex I repair mechanism, thereby providing the first example to our knowledge of a disease resulting from impaired exchange of assembled respiratory chain subunits

Sampling for pharmaceuticals and personal care products (PPCPs) and illicit drugs in wastewater systems: Are your conclusions valid? A critical review

The analysis of 87 peer-reviewed journal articles reveals that sampling for pharmaceuticals and personal care products (PPCPs) and illicit drugs in sewers and sewage treatment plant influents is mostly carried out according to existing tradition or standard laboratory protocols. Less than 5% of all studies explicitly consider internationally acknowledged guidelines or methods for the experimental design of monitoring campaigns. In the absence of a proper analysis of the system under investigation, the importance of short-term pollutant variations was typically not addressed. Therefore, due to relatively long sampling intervals, potentially inadequate sampling modes, or insufficient documentation, it remains unclear for the majority of reviewed studies whether observed variations can be attributed to "real" variations or if they simply reflect sampling artifacts. Based on results from previous and current work, the present paper demonstrates that sampling errors can lead to overinterpretation of measured data and ultimately, wrong conclusions. Depending on catchment size, sewer type, sampling setup, substance of interest, and accuracy of analytical method, avoidable sampling artifacts can range from "not significant" to "100% or more" for different compounds even within the same study. However, in most situations sampling errors can be reduced greatly, and sampling biases can be eliminated completely, by choosing an appropriate sampling mode and frequency. This is crucial, because proper sampling will help to maximize the value of measured data for the experimental assessment of the fate of PPCPs as well as for the formulation and validation of mathematical models. The trend from reporting presence or absence of a compound in "clean" water samples toward the quantification of PPCPs in raw wastewater requires not only sophisticated analytical methods but also adapted sampling methods. With increasing accuracy of chemical analyses, inappropriate sampling increasingly represents the majorsource of inaccuracy. A condensed step-by-step Sampling Guide is proposed as a starting point for future studies. © 2010 American Chemical Society

Anatomie von Kommunikationsrollen. Methoden zur Identifizierung von Akteursrollen in gerichteten Netzwerken.

Die Identifizierung von generalisierbaren Akteursrollen in sozialen Systemen ist seit jeher ein zentrales Anliegen der Sozialwissenschaften. Dies gilt insbesondere für die Identifizierung von Kommunikationsrollen, um die überaus komplexen Prozesse der interpersonalen und massenmedialen Kommunikation systematisch zu beschreiben und zu verstehen. Der vorliegende Beitrag zeigt auf, welche theoretischen und methodischen Überlegungen bei der Operationalisierung von Akteursrollen in gerichteten Netzwerken zu berücksichtigen sind. Basierend auf einer netzwerkanalytischen Betrachtung werden zum einen Unzulänglichkeiten in bestehenden Operationalisierungen von Kommunikationsrollen aufgezeigt und zum anderen neue Konzepte vorgeschlagen. Die diskutierten Konzepte lassen sich zwei unterschiedlichen Ansätzen zuordnen. Einerseits können Mikrostrukturen wie dyadische und triadische Ego Rollen als Basis für die Operationalisierung verwendet werden und andererseits kann man von der Gesamtstruktur des Netzwerks ausgehen. Für den ersten Fall werden unterschiedliche Aggregationsregeln diskutiert, welche eine Anwendung in komplexeren Netzwerken ermöglichen. Beim zweiten Ansatz, der Berücksichtigung der Gesamtstruktur, werden die Eignung unterschiedlicher Zentralitätsmaße, das Konzept des Blockmodelling und die hierarchische Strukturanalyse besprochen. Zwecks Anschaulichkeit beschränkt sich dieser Beitrag auf Rollen in Kommunikationsnetzwerken. Die vorgestellten Konzepte sind jedoch auch auf andere Netzwerke übertragbar, die aus gerichteten Beziehungen bestehen. ----------------------------------------------------------- The identification of generalizable roles in social systems has been one of the most central issues in social science ever since. Particularly in the field of interpersonal communication, the notion of communication roles has been used to describe and better understand the complex processes in social groups and society. This contribution identifies the theoretical and methodological concepts that have to be considered when roles in directed networks are operationalized. Based on a network analytic approach and critically evaluating the shortcomings of some widely used models, this study aims to propose new concepts for the operationalization of communication roles. These concepts can be divided into two distinctive approaches. One possibility is to use microstructures like dyadic and triadic communication roles as basic units. For this approach, different aggregation rules are discussed which are necessary for their application in more complex networks. The second approach takes the overall structure of a network into ac-count and identifies different roles by applying centrality measures, blockmodelling or hierarchical structure analysis tools. For illustrative reasons, this study limits its focus on the operationalization of communication roles as a prominent object in social science research. The concepts presented, however, are applicable for directed graphs in general