Correction: Luedemann et al. Prostate Cancer-Associated miRNAs in Saliva: First Steps to an Easily Accessible and Reliable Screening Tool. 2022, , 1366.

The authors wish to make the following corrections to their paper [...

Prostate Cancer-Associated miRNAs in Saliva: First Steps to an Easily Accessible and Reliable Screening Tool.

Background: Common diagnostic tools for prostate cancer-prostate-specific antigen and transrectal biopsy-show only low predictive value and poor sensitivity. This study examines circulating miRNA in saliva to explore the possibility of a non-invasive and easy-to-execute diagnostic tool for prostate cancer screenings.

Methods: 16 miRNAs were extracted from salivary exosomes and analyzed via the delta-CT method.

MicroRNAs from urinary exosomes as alternative biomarkers in the differentiation of benign and malignant prostate diseases.

Introduction:: Prostate cancer (PCa) is the second most frequently diagnosed cancer and the fifth most cancer-related cause of death worldwide. Various tools are used in the diagnosis of PCa, such as the Prostate-Specific Antigen (PSA) value or digital rectal examination. A final differentiation from benign prostate diseases such as benign prostatic hyperplasia (BPH) can often only be made by a transrectal prostate biopsy.

Small RNAs as biomarkers to differentiate benign and malign prostate diseases: An alternative for transrectal punch biopsy of the prostate?

Prostate cancer (PCa) is the most common cancer and the third most frequent cause of male cancer death in Germany. MicroRNAs (miRNA) appear to be involved in the development and progression of PCa. A diagnostic differentiation from benign prostate hyperplasia (BPH) is often only possible through transrectal punch biopsy.

Binary symbolic dynamics analysis to detect stress-associated changes of nonstationary heart rate variability.

Psychological stress may have harmful physiological effects and result in deteriorating health. Acute psychological stress acts also on cardiac autonomic regulation and may lead to nonstationarities in the interbeat interval series. We address the requirement of stationary RR interval series to calculate frequency domain parameters of heart rate variability (HRV) and use binary symbolic dynamics derived from RR interval differences to overcome this obstacle.

Stress-associated changes in salivary microRNAs can be detected in response to the Trier Social Stress Test: An exploratory study.

Stress is an important co-factor for the genesis and maintenance of many diseases and is known to have an effect on gene expression via epigenetic regulation. MicroRNAs (miRNAs) appear to function as one of the key factors of this regulation. This is the first study to investigate the response of 11 stress-associated miRNAs in human saliva - as a non-invasive source - in an experimental condition of acute psychological stress, and also their correlation with established psychological (subjective stress perception), physiological (heart rate and heart rate variability) and biochemical stress parameters (salivary cortisol and alpha-amylase).

MicroRNAs in Psychological Stress Reactions and Their Use as Stress-Associated Biomarkers, Especially in Human Saliva.

MicroRNAs (miRNAs) play a central role in the regulation of many cellular processes including physiological and psychological stress reaction pathways. Psychological stress is an important factor for the genesis and maintenance of many diseases. Several miRNAs have already been described to be involved in its regulation.

Orthoformimycin, a selective inhibitor of bacterial translation elongation from Streptomyces containing an unusual orthoformate.

Upon high throughput screening of 6700 microbial fermentation extracts, we discovered a compound, designated orthoformimycin, capable of inhibiting protein synthesis in vitro with high efficiency. The molecule, whose structure was elucidated by chemical, spectrometric, and spectroscopic methods, contains an unusual orthoformate moiety (hence the name) and belongs to a novel class of translation inhibitors. This antibiotic does not affect any function of the 30S ribosomal subunit but binds to the 50S subunit causing inhibition of translation elongation and yielding polypeptide products of reduced length.

Ribosome clearance by FusB-type proteins mediates resistance to the antibiotic fusidic acid.

Resistance to the antibiotic fusidic acid (FA) in the human pathogen Staphylococcus aureus usually results from expression of FusB-type proteins (FusB or FusC). These proteins bind to elongation factor G (EF-G), the target of FA, and rescue translation from FA-mediated inhibition by an unknown mechanism. Here we show that the FusB family are two-domain metalloproteins, the C-terminal domain of which contains a four-cysteine zinc finger with a unique structural fold.

Distinct functions of elongation factor G in ribosome recycling and translocation.

Elongation factor G (EF-G) promotes the translocation step in bacterial protein synthesis and, together with ribosome recycling factor (RRF), the disassembly of the post-termination ribosome. Unlike translocation, ribosome disassembly strictly requires GTP hydrolysis by EF-G. Here we report that ribosome disassembly is strongly inhibited by vanadate, an analog of inorganic phosphate (Pi), indicating that Pi release is required for ribosome disassembly.

Role and timing of GTP binding and hydrolysis during EF-G-dependent tRNA translocation on the ribosome.

The translocation of tRNA and mRNA through the ribosome is promoted by elongation factor G (EF-G), a GTPase that hydrolyzes GTP during the reaction. Recently, it was reported that, in contrast to previous observations, the affinity of EF-G was much weaker for GTP than for GDP and that ribosome-catalyzed GDP-GTP exchange would be required for translocation [Zavialov AV, Hauryliuk VV, Ehrenberg M (2005) J Biol 4:9]. We have reinvestigated GTP/GDP binding and show that EF-G binds GTP and GDP with affinities in the 20 to 40 microM range (37 degrees C), in accordance with earlier reports.

Control of phosphate release from elongation factor G by ribosomal protein L7/12.

Ribosomal protein L7/12 is crucial for the function of elongation factor G (EF-G) on the ribosome. Here, we report the localization of a site in the C-terminal domain (CTD) of L7/12 that is critical for the interaction with EF-G. Single conserved surface amino acids were replaced in the CTD of L7/12.

Mechanisms of elongation on the ribosome: dynamics of a macromolecular machine.

Protein synthesis in the cell is performed on ribosomes, large ribonucleoprotein particles, which in bacteria consist of three RNA molecules and over 50 proteins. This review summarizes recent progress in understanding the mechanisms of the elongation phase of protein synthesis. Results from rapid kinetic analysis of elongation reactions are discussed in the light of recent structural data.

Conformational changes of the small ribosomal subunit during elongation factor G-dependent tRNA-mRNA translocation.

Translocation, a coordinated movement of two tRNAs together with mRNA on the ribosome, is catalyzed by elongation factor G (EF-G). The reaction is accompanied by conformational rearrangements of the ribosome that are, as yet, not well characterized. Here, we analyze those rearrangements by restricting the conformational flexibility of the ribosome by antibiotics binding to specific sites of the ribosome.

An elongation factor G-induced ribosome rearrangement precedes tRNA-mRNA translocation.

The elongation cycle of protein synthesis is completed by translocation, a rearrangement during which two tRNAs bound to the mRNA move on the ribosome. The reaction is promoted by elongation factor G (EF-G) and accelerated by GTP hydrolysis. Here we report a pre-steady-state kinetic analysis of translocation.

Coupling of GTP hydrolysis by elongation factor G to translocation and factor recycling on the ribosome.

The translocation step of elongation entails the coordinated movement of tRNA and mRNA on the ribosome. Translocation is promoted by elongation factor G (EF-G) and accompanied by GTP hydrolysis, which affects both translocation and turnover of EF-G. Both reactions are much slower (50-100-fold) when GTP is replaced with non-hydrolyzable GTP analogues or GDP, indicating that the reaction rates are determined by conformational transitions induced by GTP hydrolysis.

[Mechanism of tRNA translocation on the ribosome].

During the translocation step of the elongation cycle of peptide synthesis two tRNAs together with the mRNA move synchronously and rapidly on the ribosome. Translocation is catalyzed by the elongation factor G (EF-G) and requires GTP hydrolysis. The fundamental biochemical features of the process were worked out in the 1970-80s, to a large part by A.

Conformationally restricted elongation factor G retains GTPase activity but is inactive in translocation on the ribosome.

Elongation factor G (EF-G) from Escherichia coli is a large, five-domain GTPase that promotes tRNA translocation on the ribosome. Full activity requires GTP hydrolysis, suggesting that a conformational change of the factor is important for function. To restrict the intramolecular mobility, two cysteine residues were engineered into domains 1 and 5 of EF-G that spontaneously formed a disulfide cross-link.

GTPases mechanisms and functions of translation factors on the ribosome.

The elongation factors (EF) Tu and G and initiation factor 2 (IF2) from bacteria are multidomain GTPases with essential functions in the elongation and initiation phases of translation. They bind to the same site on the ribosome where their low intrinsic GTPase activities are strongly stimulated. The factors differ fundamentally from each other, and from the majority of GTPases, in the mechanisms of GTPase control, the timing of Pi release, and the functional role of GTP hydrolysis.

Role of domains 4 and 5 in elongation factor G functions on the ribosome.

Elongation factor G (EF-G) is a large, five domain GTPase that catalyses the translocation of the tRNAs on the bacterial ribosome at the expense of GTP. In the crystal structure of GDP-bound EF-G, domain 1 (G domain) makes direct contacts with domains 2 and 5, whereas domain 4 protrudes from the body of the molecule. Here, we show that the presence of both domains 4 and 5 is essential for tRNA translocation and for the turnover of the factor on the ribosome, but not for rapid single-round GTP hydrolysis by EF-G.

Late events of translation initiation in bacteria: a kinetic analysis.

Binding of the 50S ribosomal subunit to the 30S initiation complex and the subsequent transition from the initiation to the elongation phase up to the synthesis of the first peptide bond represent crucial steps in the translation pathway. The reactions that characterize these transitions were analyzed by quench-flow and fluorescence stopped-flow kinetic techniques. IF2-dependent GTP hydrolysis was fast (30/s) followed by slow P(i) release from the complex (1.

Stimulation of the GTPase activity of translation elongation factor G by ribosomal protein L7/12.

Elongation factors (EFs) Tu and G are GTPases that have important functions in protein synthesis. The low intrinsic GTPase activity of both factors is strongly stimulated on the ribosome by unknown mechanisms. Here we report that isolated ribosomal protein L7/12 strongly stimulates GTP hydrolysis by EF-G, but not by EF-Tu, indicating a major contribution of L7/12 to GTPase activation of EF-G on the ribosome.