Funktionelle Selektivität am Beispiel des β2-Adrenozeptors(S. 130)
Roland Seifert, Michael Reinartz
Originally, G protein-coupled receptors were assumed to act as on-off switches, adopting either an active (R*) or inactive (R) conformation. However, pharmacological and biophysical studies over the past 15–20 years have now unequivocally shown that receptors can exist in multiple active conformations with distinct capabilities to activate effectors. This concept is referred to as functional selectivity and has important implications for future drug design. Here, we discuss this fundamental pharmacological concept using the β2-adrenoceptor as paradigm.
Somatische Tumormutationen eröffnen neue Therapieoptionen(S. 136)
Olaf Riess, Christopher Schroeder, Peter Bauer, Falco Fend
Prognostic or predictive somatic genetic biomarkers influence therapeutic decisions in oncology. With the availability of next-generation sequencing (NGS) technologies, large numbers of somatic and germ line mutations can be analysed in parallel both, from formalin-fixed, paraffin-embedded tissue (FFPE) and fresh frozen tissue at high quality. In this study we evaluated the feasibility, turn-around time and diagnostic usefulness of highthroughput NGS analyses in the clinical setting and offered two different diagnostic sequencing panels to 52 selected patients.
Wie schützen sich Larven der Juwelwespe vor schädlichen Mikroben?(S. 142)
Larvae of the emerald cockroach wasp, Ampulex compressa, sanitize their cockroach hosts, Periplaneta americana, with a blend of antimicrobials comprising mainly (R)-(–)-mellein and micromolide. The larval secretion inhibits growth of the Gram-negative entomopathogen Serratia marcescens as well as the Gram-positive Staphylococcus hyicus. Our results suggest that the larval secretion protects the wasp larvae from a wide range of antagonistic microbes.
Vitamin-produzierende Symbionten in Feuerwanzen(S. 144)
Microbial symbionts play an essential role for the ecology and evolution of most multicellular organisms. Firebugs (Hemiptera, Pyrrhocoridae) are associated with actinobacterial symbionts in the mid-gut that supplement limiting B-vitamins and are tightly integrated into the host’s metabolism. The symbiosis is widespread among firebugs and enables them to subsist on Malvales seeds as the sole nutritional resource.
Der Zebrabärbling als Modell für die Regeneration von Nervengewebe(S. 148)
Marco Ferg, Sepand Rastegar, Uwe Strähle
In contrast to mammals where the formation of new neurons in the adult is very limited, teleost fish like the zebrafish form new neurons abundantly and have a high regenerative potential to repair lesions of the central nervous system. These news neurons will integrate into the existing neuronal networks. The challenge will be to unravel the molecular mechanisms of nervous tissue regeneration in zebrafish in the hope to employ this knowledge for development of new therapies for human patients.
Biologisch aktive Naturstoffe aus Cyanobakterien der Gattung Nostoc(S. 151)
Timo H. J. Niedermeyer
Secondary metabolites from many organisms have been studied extensively in the past, and indispensable drug substances have been approved that are based on these compounds. Microalgae have long been neglected by natural product scientists. In recent years, however, cyanobacteria have been recognized as prolific producers of potent bioactive metabolites. This review takes a closer look at some of the natural products that have been isolated from the genus Nostoc.
Abbildung mikrobieller Zelloberflächen(S. 154)
Visualizing the microbial cell surface by microscopy has been and still is a challenge. Fluorescence light-optical methods locate structures with accuracy in the lower nanometer range, scanning force microscopes record corrugations with angstrom sensitivity, and electron microscopy provides near atomic resolution of protein complexes. But if the surface of intact cells is to be investigated we are limited by several restrictions. What can microscopy achieve and which method is promising?
In silico-Funktions- und Strukturvorhersagen bei Proteinen(S. 158)
Extremely sensitive tools for protein sequence searching have been developed that rely on the pairwise comparison of multiple sequence alignments instead of single sequences. Such tools detect homologous relationships over billions of years of evolution, down to the midnight zone of sequence alignment where less than 20 percent of residues are identical. Homologous relationships yield valuable hypotheses about the structure and molecular functions of proteins, and even orthologous relationships with proteins in model organisms may be found.
Transkriptom-Sequenzierung in der Alternsforschung(S. 163)
Marco Groth, Kathrin Reichwald, Karol Szafranski, Stefan Taudien, Matthias Platzer
With the advent of next-generation sequencing technologies transcriptome sequencing (RNA-seq) became widely used to study the genetic background of ageing processes and related diseases. We describe the power of this method in the study of two novel age research model organisms, the short-lived killifish Nothobranchius furzeri and the long-lived naked mole rat Heterocephalus glaber. A third example illustrates the utility of RNA-seq in a multispecies approach elucidating the role of mild stress in healthy ageing.
Next Generation Sequencing in der mikrobiellen (Meta)Genomforschung(S. 168)
In the past two decades genome sequencing was getting more and more one of the most important research fields of life sciences. It was accelerated by the introduction of the next-generation sequencing technologies in 2005. With the further development of the technologies today, there is a bride field of features and applications that one can use for genome research.
Eigenschaften von Bakterien aus Schwermetall-kontaminierten Halden(S. 172)
Franziska Lederer, Tobias J. Günther, Johannes Raff, Katrin Pollmann, Katrin Flemming
Bacterial isolates from a uranium mining waste pile are adapted in a very special kind of way to their heavy metal contaminated environment. Genome analyses identified many genes that might support the incidence of these strains in their special habitat. Using the next-generation sequencing technology multiple surface (S-) layer genes and different kinds of metal transporter genes were identified. These data give the genetic affirmation that these strains are adapted substantial to their environment. 10.1007/s12268-014-0
Anwendungen & Produkte
Qualitätskontrolle von Nukleinsäuren(S. 182)
Implementing rigorous quality control (QC) steps at appropriate breakpoints across nucleic acid based workflows enables researchers to eliminate samples that do not meet the quality criteria required for downstream processes. Such an approach reduces the risk of repeat experiments, can result in significant time savings and ensure tighter budget control.
Identifikation von Tumorstammzellen in gemischten Populationen(S. 185)
Don Weldon, Steve McClellan
A new technology allows target RNA levels to be determined within individual live cells, without damaging the cells. The new probes enable labelling and sorting of cancer stem cells based on the expression of target mRNA transcripts from human tumour samples. The technology works across many solid tumour types and bypasses the use of surface markers and functional assays, simplifying the process of accurately identifying and isolating cancer stem cells.
Biosensoren für die mikrobielle Stamm - entwicklung im Hochdurchsatzformat(S. 228)
Georg Schendzielorz, Stephan Binder, Jan Marienhagen
Microbial strain development for the biotechnological production of small molecules is time-consuming and laborious. This can be attributed to the fact that increased product formation usually does not confer a phenotype, which would allow interfacing with high-throughput screening technologies. Recently, advances were made in the construction of biosensors for detecting small molecules at the single cell level and first examples for their application in combination with FACS demonstrate the potential of such biosensors for microbial strain development.
Gerichtete Editierung – ein Werkzeug zur Reprogrammierung von RNA(S. 231)
Adenosine-to-inosine RNA editing allows for reprogramming genetic information on the RNA level. We have re-engineered human ADAR proteins into guide-RNA-dependent enzymes in order to obtain a tool for the siteselective manipulation of arbitrary RNAs. In the future such a tool could be used to understand the crosstalk of editing and RNA processing or for the on/off-switching of disease-related point mutations.