Molecular basis of bacterial resistance to chloramphenicol and florfenicol

Chloramphenicol (Cm) and its fluorinated derivative florfenicol (Ff) represent highly potent inhibitors of bacterial protein biosynthesis. As a consequence of the use of Cm in human and veterinary medicine, bacterial pathogens of various species and genera have developed and/or acquired Cm resistance. Ff is solely used in veterinary medicine and has been introduced into clinical use in the mid-1990s. Of the Cm resistance genes known to date, only a small number also mediates resistance to Ff. In this review, we present an overview of the different mechanisms responsible for resistance to Cm and Ff with particular focus on the two different types of chloramphenicol acetyltransferases (CATs), specific exporters and multidrug transporters. Phylogenetic trees of the different CAT proteins and exporter proteins were constructed on the basis of a multisequence alignment. Moreover, information is provided on the mobile genetic elements carrying Cm or Cm/Ff resistance genes to provide a basis for the understanding of the distribution and the spread of Cm resistance--even in the absence of a selective pressure imposed by the use of Cm or Ff.     

The Process-inducing Activity of Transmembrane Agrin Requires Follistatin-like Domains

Clustering or overexpression of the transmembrane form of the extracellular matrix proteoglycan agrin in neurons results in the formation of numerous highly motile filopodia-like processes extending from axons and dendrites. Here we show that similar processes can be induced by overexpression of transmembrane-agrin in several non-neuronal cell lines. Mapping of the process-inducing activity in neurons and non-neuronal cells demonstrates that the cytoplasmic part of transmembrane agrin is dispensable and that the extracellular region is necessary for process formation. Site-directed mutagenesis reveals an essential role for the loop between β-sheets 3 and 4 within the Kazal subdomain of the seventh follistatin-like domain of TM-agrin. An aspartic acid residue within this loop is critical for process formation. The seventh follistatin-like domain could be functionally replaced by the first and sixth but not by the eighth follistatin-like domain, demonstrating a functional redundancy among some follistatin-like domains of agrin. Moreover, a critical distance of the seventh follistatin-like domain to the plasma membrane appears to be required for process formation. These results demonstrate that different regions within the agrin protein are responsible for synapse formation at the neuromuscular junction and for process formation in central nervous system neurons and suggest a role for agrin''s follistatin-like domains in the developing central nervous system.     

Study of the combined effects of PTH treatment and mechanical loading in postmenopausal osteoporosis using a new mechanistic PK-PD model

Biomechanics and Modeling in Mechanobiology - One of only a few approved and available anabolic treatments for severe osteoporosis is daily injections of PTH (1-34). This drug has a specific dual...     

Supply versus use designs of environmental extensions in input–output analysis: Conceptual and empirical implications for the case of energy

Input–output analysis is one of the central methodological pillars of industrial ecology. However, the literature that discusses different structures of environmental extensions (EEs), that is, the scope of physical flows and their attribution to sectors in the monetary input–output table (MIOT), remains fragmented. This article investigates the conceptual and empirical implications of applying two different but frequently used designs of EEs, using the case of energy accounting, where one represents energy supply while the other energy use in the economy. We derive both extensions from an official energy supply–use dataset and apply them to the same single‐region input–output (SRIO) model of Austria, thereby isolating the effect that stems from the decision for the extension design. We also crosscheck the SRIO results with energy footprints from the global multi‐regional input–output (GMRIO) dataset EXIOBASE. Our results show that the ranking of footprints of final demand categories (e.g., household and export) is sensitive to the extension design and that product‐level results can vary by several orders of magnitude. The GMRIO‐based comparison further reveals that for a few countries the supply‐extension result can be twice the size of the use‐extension footprint (e.g., Australia and Norway). We propose a graph approach to provide a generalized framework to disclosing the design of EEs. We discuss the conceptual differences between the two extension designs by applying analogies to hybrid life‐cycle assessment and conclude that our findings are relevant for monitoring of energy efficiency and emission reduction targets and corporate footprint accounting.     

Pontine A5 region modulation of the cardiorespiratory response evoked from the midbrain dorsolateral periaqueductal grey

Journal of Physiology and Biochemistry - Connections between the midbrain dorsolateral periaqueductal grey (dlPAG) and the pontine A5 region have been shown. The stimulation of both regions evokes...