Modelle studentischer Partizipation an Hochschulen im Bereich Lehramt – das Passauer Referat 4: „Studierendenvertretung Lehramt“ als Beispiel guter Praxis in der Lehrerinnen- und Lehrerbildung

Das Referat 4 versteht sich aufbauend auf der Entsendung seiner Mitglieder aus den verschiedenen Fachschaften sowie seinen einzelnen Schwerpunktsetzungen als Interessenvertretung und Schnittstelle zwischen allen Studierenden und Dozierenden der Lehrerinnen- und Lehrerbildung an der Universität Passau, als Impulsgeber, Anlaufstelle und Kommunikationsorgan in verschiedene Richtungen. Es dient seinem Selbstverständnis nach als Sprachrohr der Studierenden und unterstützt andere studentische Vertretungsorgane im Bereich der Lehrerinnen- und Lehrerbildung

Laying the foundations for a bio-economy

Biological technologies are becoming an important part of the economy. Biotechnology already contributes at least 1% of US GDP, with revenues growing as much as 20% annually. The introduction of composable biological parts will enable an engineering discipline similar to the ones that resulted in modern aviation and information technology. As the sophistication of biological engineering increases, it will provide new goods and services at lower costs and higher efficiencies. Broad access to foundational engineering technologies is seen by some as a threat to physical and economic security. However, regulation of access will serve to suppress the innovation required to produce new vaccines and other countermeasures as well as limiting general economic growth

Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing.

Chitin is a highly abundant polysaccharide in nature and is linked to immune recognition of fungal infections and asthma in humans. Ubiquitous in fungi and insects, chitin is absent inmammals and plants and, thus, represents a microbeassociatedmolecular pattern (MAMP). However, highly polymeric chitin is insoluble, which potentially hampers recognition by host immune sensors. In plants, secreted chitinases degrade polymeric chitin into diffusible oligomers, which are "fed to" innate immune receptors and co-receptors. In human and murine immune cells, a similar enzymatic activity was shown for human chitotriosidase (CHIT1), and oligomeric chitin is sensed via an innate immune receptor, Toll-like receptor (TLR) 2. However, a complete system of generating MAMPs from chitin and feeding them into a specific receptor/co-receptor-aided sensing mechanism has remained unknown in mammals. The effect of the secreted chitinolytic host enzyme, CHIT1, on the TLR2 activity of polymeric chitin preparations from shrimps, house dust mites and the fungal pathogen Candida albicans was assessed in vitro using cell lines and primary immune cells. Moreover, the regulation of CHIT1 was analyzed. Here, we show that CHIT1 converts inert polymeric chitin into diffusible oligomers that can be sensed by TLR1/TLR2 co-receptor/receptor heterodimers, a process promoted by the lipopolysaccharide binding protein (LBP) and CD14. Furthermore, we observed that Chit1 is induced via the b-glucan receptor Dectin-1 upon direct contact of immortalized human macrophages to the fungal pathogen Candida albicans, whereas the defined fungal secreted aspartyl proteases, Sap2 and Sap6, from C. albicans were able to degrade CHIT1 in vitro. Our study shows the existence of an inducible system of MAMP generation in the human host that enables contact-independent immune activation by diffusible MAMP ligands with a striking similarity to the plant kingdom. Moreover, this study highlights CHIT1 as a potential therapeutic target for TLR2-mediated inflammatory processes that are fueled by oligomeric chitin

Optimization of Ribosome Structure and Function by rRNA Base Modification

BACKGROUND: Translating mRNA sequences into functional proteins is a fundamental process necessary for the viability of organisms throughout all kingdoms of life. The ribosome carries out this process with a delicate balance between speed and accuracy. This work investigates how ribosome structure and function are affected by rRNA base modification. The prevailing view is that rRNA base modifications serve to fine tune ribosome structure and function. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, yeast strains deficient in rRNA modifications in the ribosomal peptidyltransferase center were monitored for changes in and translational fidelity. These studies revealed allele-specific sensitivity to translational inhibitors, changes in reading frame maintenance, nonsense suppression and aa-tRNA selection. Ribosomes isolated from two mutants with the most pronounced phenotypic changes had increased affinities for aa-tRNA, and surprisingly, increased rates of peptidyltransfer as monitored by the puromycin assay. rRNA chemical analyses of one of these mutants identified structural changes in five specific bases associated with the ribosomal A-site. CONCLUSIONS/SIGNIFICANCE: Together, the data suggest that modification of these bases fine tune the structure of the A-site region of the large subunit so as to assure correct positioning of critical rRNA bases involved in aa-tRNA accommodation into the PTC, of the eEF-1A•aa-tRNA•GTP ternary complex with the GTPase associated center, and of the aa-tRNA in the A-site. These findings represent a direct demonstration in support of the prevailing hypothesis that rRNA modifications serve to optimize rRNA structure for production of accurate and efficient ribosomes

Base methylations in the double-stranded RNA by a fused methyltransferase bearing unwinding activity

Modifications of rRNAs are clustered in functional regions of the ribosome. In Helix 74 of Escherichia coli 23S rRNA, guanosines at positions 2069 and 2445 are modified to 7-methylguanosine(m7G) and N2-methylguanosine(m2G), respectively. We searched for the gene responsible for m7G2069 formation, and identified rlmL, which encodes the methyltransferase for m2G2445, as responsible for the biogenesis of m7G2069. In vitro methylation of rRNA revealed that rlmL encodes a fused methyltransferase responsible for forming both m7G2069 and m2G2445. We renamed the gene rlmKL. The N-terminal RlmL activity for m2G2445 formation was significantly enhanced by the C-terminal RlmK. Moreover, RlmKL had an unwinding activity of Helix 74, facilitating cooperative methylations of m7G2069 and m2G2445 during biogenesis of 50S subunit. In fact, we observed that RlmKL was involved in the efficient assembly of 50S subunit in a mutant strain lacking an RNA helicase deaD

Synthetic biology: ethical ramifications 2009

During 2007 and 2008 synthetic biology moved from the manifesto stage to research programs. As of 2009, synthetic biology is ramifying; to ramify means to produce differentiated trajectories from previous determinations. From its inception, most of the players in synthetic biology agreed on the need for (a) rationalized design and construction of new biological parts, devices, and systems as well as (b) the re-design of natural biological systems for specified purposes, and that (c) the versatility of designed biological systems makes them suitable to address such challenges as renewable energy, the production of inexpensive drugs, and environmental remediation, as well as providing a catalyst for further growth of biotechnology. What is understood by these goals, however, is diverse. Those assorted understandings are currently contributing to different ramifications of synthetic biology. The Berkeley Human Practices Lab, led by Paul Rabinow, is currently devoting its efforts to documenting and analyzing these ramifications as they emerge

A Forward-Genetic Screen and Dynamic Analysis of Lambda Phage Host-Dependencies Reveals an Extensive Interaction Network and a New Anti-Viral Strategy

Latently infecting viruses are an important class of virus that plays a key role in viral evolution and human health. Here we report a genome-scale forward-genetics screen for host-dependencies of the latently-infecting bacteriophage lambda. This screen identified 57 Escherichia coli (E. coli) genes—over half of which have not been previously associated with infection—that when knocked out inhibited lambda phage's ability to replicate. Our results demonstrate a highly integrated network between lambda and its host, in striking contrast to the results from a similar screen using the lytic-only infecting T7 virus. We then measured the growth of E. coli under normal and infected conditions, using wild-type and knockout strains deficient in one of the identified host genes, and found that genes from the same pathway often exhibited similar growth dynamics. This observation, combined with further computational and experimental analysis, led us to identify a previously unannotated gene, yneJ, as a novel regulator of lamB gene expression. A surprising result of this work was the identification of two highly conserved pathways involved in tRNA thiolation—one pathway is required for efficient lambda replication, while the other has anti-viral properties inhibiting lambda replication. Based on our data, it appears that 2-thiouridine modification of tRNAGlu, tRNAGln, and tRNALys is particularly important for the efficient production of infectious lambda phage particles

Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex

The 5′-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5′-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2′-O positions, catalyzed by nsp14 N7-MTase and nsp16 2′-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2′-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs

Interface chip for random number generation in 350nm CMOS

Zusammenfassung in englischer SpracheIn dieser Arbeit wurde eine analoge Auswerteschaltung entworfen und gefertigt, die aus den Ausgangspulsen einer integrierten LED-SPAD-Quencher Kombination, Zufallszahlen bereitstellt. Die Zufallszahlen werden durch den Vergleich der Zeitabstände zwischen aufeinanderfolgenden Detektionen der SPAD ermittelt, wobei das Design darauf abzielt, eine vollständig integrierbare Lösung zu ermöglichen. Zu diesem Zweck wurde die Schaltung in einem 350nm CMOS Prozess entwickelt, wobei eine Konstantstromquelle genutzt wird, um den Zeitvergleich zweier Intervalle, durch Ladung und Entladung eines Kondensators, durchzuführen. Die Auswertung des Messergebnisses übernimmt ein Komparator mit extern abgleichbarem Offset. Eine Signalaufbereitung mit nachfolgendem Verstärker sorgt für definierte Ausgangssignale, in 3,3V CMOS-Logik, der Schaltung und die Möglichkeit eine Last von 50 Ohm treiben zu können. Es wird das entwickelte Schaltungskonzept vorgestellt und mit Hilfe von Simulationen deren Funktionsfähigkeit unterlegt.Weiters ist ein Chip produziert und in Betrieb genommen worden. Die aufgenommenen Zufallszahlen werden durch ein Testprogramm des National Institute of Standards and Technology (NIST) kontrolliert. Die Schaltung ist im Stande zwei aufeinanderfolgende Zeitintervalle im Bereich von 10 ns bis 10 µs zu vergleichen. Die Leistungsaufnahme der, mit 3,3V versorgten, Auswerteschaltung ist, je nach Impulsfolge, im Bereich von 1,1mW bis 4,55mW gemessen worden. Es wurde erreicht, dass eine 2 Gbit lange binäre Zufallszahlenfolge, nach einer Bearbeitung mittels "XOR-Hashing" (Reduktion auf 1 Gbit), alle NIST-Tests schafft.This thesis shows the development of an interface circuit which allows the use of a LEDSPAD-Quencher combination as a quantum random number generator. The random bits are created by comparison of two consecutive time intervals between photon detection events of the SPAD. With this on-chip solution a fully integrated approach for such a random number generator is presented. For this purpose a circuit in 350nm CMOS has been designed which executes the comparison by charging and decharging a capacitor with a constant current source. A comparator design which allows to compensate it's offset with an external voltage is used to evaluate the result of the comparison by measuring the polarity of the capacitor voltage. A postprocessing circuit followed by an output stage provides well defined output signals for 3,3V CMOS logic at a load of 50 Ohm. Simulations as well as measurements of a developed chip design are presented and confirm the functionality of the circuit. Random number sequences are recorded and analyzed with the help of the statistical test suite from the National Institude of Standards and Technology (NIST). The chip is capable of comparing two consecutive time intervalls with durations from 10 ns to 10 µs. The power consumption of the interface circuit starts from 1,1mW and can reach up to 4,55mW depending on the pulse repetition rate delivered from the SPAD. The supply voltage of the chip is 3,3V. After using "XOR-Hashing" as post processing function which reduces a 2 Gbit random sequence to a 1 Gbit file it was possible to pass all tests provided by the NIST Test suite.7