Untersuchungen zum Einfluss niederenergetischer elektromagnetischer Felder auf die Prolieferation von Gefäßwandzellen in vitro

Eigene in vitro-Untersuchungen zeigten, dass elektromagnetische Felder einen positiven Einfluss auf die Proliferation von Gefäßwandzellen haben. Weitergehend wurde versucht, diese Veränderungen auf Proteinebene (Westernblot) zu untersuchen. Dazu wurden koronare glatte Muskelzellen vom Rind (bov cSMC) und humane Endothellzellen (EC) einem elektromagnetischen Feld mit verschiedenen Frequenzen für unterschiedliche Zeiträume ausgesetzt. Die Experimente wurden mit proliferierenden und ruhenden Zellen durchgeführt. Eine Aufarbeitung erfolgte 24h und 48h nach Exposition. Die Proteine alpha-Actin und Calponin (Phänotypenmarker) und PCNA (Proliferationsmarker) wurden untersucht. Mittels Westernblot konnten o.g. Parameter nachgewiesen werden, allerdings konnte keine offensichtliche Veränderung der Expression gezeigt werden. Die proproliferativen Effekte elektromagnetischer Felder scheinen für einen Nachweis proliferationsassoziierter Parameter mittels Westernblot zu schwach ausgeprägt zu sein

Divergent architecture of the heterotrimeric NatC complex explains N-terminal acetylation of cognate substrates

The heterotrimeric NatC complex, comprising the catalytic Naa30 and the two auxiliary subunits Naa35 and Naa38, co-translationally acetylates the N-termini of numerous eukaryotic target proteins. Despite its unique subunit composition, its essential role for many aspects of cellular function and its suggested involvement in disease, structure and mechanism of NatC have remained unknown. Here, we present the crystal structure of the Saccharomyces cerevisiae NatC complex, which exhibits a strikingly different architecture compared to previously described N-terminal acetyltransferase (NAT) complexes. Cofactor and ligand-bound structures reveal how the first four amino acids of cognate substrates are recognized at the Naa30–Naa35 interface. A sequence-specific, ligand-induced conformational change in Naa30 enables efficient acetylation. Based on detailed structure–function studies, we suggest a catalytic mechanism and identify a ribosome-binding patch in an elongated tip region of NatC. Our study reveals how NAT machineries have divergently evolved to N-terminally acetylate specific subsets of target proteins

Antibiotic-resistant bacteria, antibiotic resistance genes, and antibiotic residues in wastewater from a poultry slaughterhouse after conventional and advanced treatments

Slaughterhouse wastewater is considered a reservoir for antibiotic-resistant bacteria and antibiotic residues, which are not sufficiently removed by conventional treatment processes. This study focuses on the occurrence of ESKAPE bacteria (Enterococcus spp., S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, Enterobacter spp.), ESBL (extended-spectrum β-lactamase)-producing E. coli, antibiotic resistance genes (ARGs) and antibiotic residues in wastewater from a poultry slaughterhouse. The efficacy of conventional and advanced treatments (i.e., ozonation) of the in-house wastewater treatment plant regarding their removal was also evaluated. Target culturable bacteria were detected only in the influent and effluent after conventional treatment. High abundances of genes (e.g., bla$_{TEM}$, bla$_{CTX-M-15}$, bla$_{CTX-M-32}$, bla$_{OXA-48}$, bla$_{CMY}$ and mcr-1) of up to 1.48 × 10$^{6}$ copies/100 mL were detected in raw influent. All of them were already significantly reduced by 1–4.2 log units after conventional treatment. Following ozonation, mcr-1 and bla$_{CTX-M-32}$ were further reduced below the limit of detection. Antibiotic residues were detected in 55.6% (n = 10/18) of the wastewater samples. Despite the significant reduction through conventional and advanced treatments, effluents still exhibited high concentrations of some ARGs (e.g., sul1, ermB and bla$_{OXA-48}$), ranging from 1.75 × 10$^{2}$ to 3.44 × 10$^{3}$ copies/100 mL. Thus, a combination of oxidative, adsorptive and membrane-based technologies should be considered

IP storage : a performance and security study, LDRD 04-1021.

Effective, high-performance, networked file systems and storage is needed to solve I/O bottlenecks between large compute platforms. Frequently, parallel techniques such as PFTP, are employed to overcome the adverse effect of TCP's congestion avoidance algorithm in order to achieve reasonable aggregate throughput. These techniques can suffer from end-system bottlenecks due to the protocol processing overhead and memory copies involved in moving large amounts of data during I/O. Moreover, transferring data using PFTP requires manual operation, lacking the transparency to allow for interactive visualization and computational steering of large-scale simulations from distributed locations. This paper evaluates the emerging Internet SCSI (iSCSI) protocol [2] as the file/data transport in order that remote clients can transparently access data through a distributed global file system available to local clients. We started our work characterizing the performance behavior of iSCSI in Local Area Networks (LANs). We then proceeded to study the effect of propagation delay on throughput using remote iSCSI storage and explored optimization techniques to mitigate the adverse effects of long delay in high-bandwidth Wide Area Networks (WANs). Lastly, we evaluated iSCSI in a Storage Area Network (SAN) for a Global Parallel Filesystem. We conducted our benchmark based on typical usage model of large-scale scientific applications at Sandia. We demonstrated the benefit of high-performance parallel VO to scientific applications at the IEEE 2004 Supercomputing Conference, using experiences and knowledge gained from this study

Divergent architecture of the heterotrimeric NatC complex explains N-terminal acetylation of cognate substrates

The heterotrimeric NatC complex, comprising the catalytic Naa30 and the two auxiliary subunits Naa35 and Naa38, co-translationally acetylates the N-termini of numerous eukaryotic target proteins. Despite its unique subunit composition, its essential role for many aspects of cellular function and its suggested involvement in disease, structure and mechanism of NatC have remained unknown. Here, we present the crystal structure of the Saccharomyces cerevisiae NatC complex, which exhibits a strikingly different architecture compared to previously described N-terminal acetyltransferase (NAT) complexes. Cofactor and ligand-bound structures reveal how the first four amino acids of cognate substrates are recognized at the Naa30–Naa35 interface. A sequence-specific, ligand-induced conformational change in Naa30 enables efficient acetylation. Based on detailed structure–function studies, we suggest a catalytic mechanism and identify a ribosome-binding patch in an elongated tip region of NatC. Our study reveals how NAT machineries have divergently evolved to N-terminally acetylate specific subsets of target proteins

What is multidisciplinary cancer care like in practice? a protocol for a mixed-method study to characterise ambulatory oncology services in the Australian public sector

© 2019 Author(s). Introduction An understanding of the real-world provision of oncology outpatient services can help maintain service quality in the face of escalating demand and tight budgets, by informing the design of interventions that improve the effectiveness or efficiency of provision. The aims of this study are threefold. First, to develop an understanding of cancer services in outpatient clinics by characterising the organisation and practice of multidisciplinary care (MDC). Second, to explore the key areas of: (a) clinical decision-making and (b) engagement with patients' supportive needs. Third, to identify barriers to, and facilitators of, the delivery of quality care in these settings. Methods and analysis A suite of mixed-methods studies will be implemented at six hospitals providing cancer outpatient clinics, with a staged roll-out. In Stage One, we will examine policies, use unstructured observations and undertake interviews with key health professionals to characterise the organisation and delivery of MDC. In Stage Two, observations of practice will continue, to deepen our understanding, and to inform two focused studies. The first will explore decision-making practices and the second will examine how staff engage with patients' needs; both studies involve interviews, to complement observation. As part of the study of supportive care, we will examine the implications of an introduction of patient-reported measures (PRMs) into care, adding surveys to interviews before and after PRMs roll-out. Data analysis will account for site-specific and cross-site issues using an adapted Qualitative Rapid Appraisal, Rigorous Analysis approach. Quantitative data from clinician surveys will be statistically analysed and triangulated with the related qualitative study findings. Ethics and dissemination Ethical approval was granted by South Eastern Sydney Local Health District Human Research Ethics Committee (no. 18/207). Findings will be shared with participating hospitals and widely disseminated through publications and presentations

Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature

This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the \u3e20 distinct compound classes is also reviewed, and commonalities are discussed

FIP200 claw domain binding to p62 promotes autophagosome formation at ubiquitin condensates

The autophagy cargo receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degradation by autophagy, but the molecular mechanism of p62 signaling to the core autophagy machinery is unclear. Here, we show that disordered residues 326-380 of p62 directly interact with the C-terminal region (CTR) of FIP200. Crystal structure determination shows that the FIP200 CTR contains a dimeric globular domain that we designated the "Claw" for its shape. The interaction of p62 with FIP200 is mediated by a positively charged pocket in the Claw, enhanced by p62 phosphorylation, mutually exclusive with the binding of p62 to LC3B, and it promotes degradation of ubiquitinated cargo by autophagy. Furthermore, the recruitment of the FIP200 CTR slows the phase separation of ubiquitinated proteins by p62 in a reconstituted system. Our data provide the molecular basis for a crosstalk between cargo condensation and autophagosome formation