When arm’s length is too far. Relationship banking over the credit cycle

Using a novel way to identify relationship and transaction banks, we study how banks’ lending techniques affect credit constraints of small and medium-sized enterprises across emerging Europe. We link the lending techniques that banks use in the direct vicinity of firms to these firms’ credit constraints at two contrasting points of the credit cycle. We show that relationship lending alleviates credit constraints during a cyclical downturn but not during a boom period. The positive impact of relationship lending in a downturn is strongest for smaller and more opaque firms and in regions where the downturn is more severe. Additional evidence suggests that the reduction in credit constraints due to relationship lending helps to mitigate the adverse impact of an economic downturn on local firm growth and does not constitute evergreening of underperforming loans

Spitting in the wind?—The challenges of RNA sequencing for biomarker discovery from saliva

Forensic trace contextualization, i.e., assessing information beyond who deposited a biological stain, has become an issue of great and steadily growing importance in forensic genetic casework and research. The human transcriptome encodes a wide variety of information and thus has received increasing interest for the identification of biomarkers for different aspects of forensic trace contextualization over the past years. Massively parallel sequencing of reverse-transcribed RNA (“RNA sequencing”) has emerged as the gold standard technology to characterize the transcriptome in its entirety and identify RNA markers showing significant expression differences not only between different forensically relevant body fluids but also within a single body fluid between forensically relevant conditions of interest. Here, we analyze the quality and composition of four RNA sequencing datasets (whole transcriptome as well as miRNA sequencing) from two different research projects (the RNAgE project and the TrACES project), aiming at identifying contextualizing forensic biomarker from the forensically relevant body fluid saliva. We describe and characterize challenges of RNA sequencing of saliva samples arising from the presence of oral bacteria, the heterogeneity of sample composition, and the confounding factor of degradation. Based on these observations, we formulate recommendations that might help to improve RNA biomarker discovery from the challenging but forensically relevant body fluid saliva

The MAP kinase MpkA controls cell wall integrity, oxidative stress response, gliotoxin production and iron adaptation in Aspergillus fumigatus

The saprophytic fungus Aspergillus fumigatus is the most important air-borne fungal pathogen. The cell wall of A. fumigatus has been studied intensively as a potential target for development of effective antifungal agents. A major role in maintaining cell wall integrity is played by the mitogen-activated protein kinase (MAPK) MpkA. To gain a comprehensive insight into this central signal transduction pathway, we performed a transcriptome analysis of the ΔmpkA mutant under standard and cell wall stress conditions. Besides genes involved in cell wall remodelling, protection against ROS and secondary metabolism such as gliotoxin, pyomelanin and pseurotin A, also genes involved in siderophore biosynthesis were regulated by MpkA. Consistently, northern and western blot analyses indicated that iron starvation triggers phosphorylation and thus activation of MpkA. Furthermore, localization studies indicated that MpkA accumulates in the nucleus under iron depletion. Hence, we report the first connection between a MAPK pathway and siderophore biosynthesis. The measurement of amino acid pools and of the pools of polyamines indicated that arginine was continuously converted into ornithine to fuel the siderophore pool in the ΔmpkA mutant strain. Based on our data, we propose that MpkA fine-tunes the balance between stress response and energy consuming cellular processes

Mineralogical characterization of scalings formed in geothermal sites in the Upper Rhine Graben before and after the application of sulfate inhibitors

Scale formation processes in the surface installations of geothermal power plants may have a negative effect on power plant performance. In addition, scales formed within the geothermal water circuit frequently accumulate natural radionuclides. Consequently, scale formation may lead to radiation dose rates, which are of radiological concern, and deposits, which may have to be disposed as radioactive waste. In order to minimize these problems and to foster geothermal power plant availability, it is of major interest to understand scale formation processes and to develop methods for their inhibition. One important pre-requisite towards this goal is a sound mineralogical and geochemical characterization of the formed material. Geothermal brines at sites in the Upper Rhine Graben are in general highly mineralized and become, upon cooling in the heat exchanger, supersaturated with respect to sulfate solid-solutions, e.g. (Ba,Sr)SO4, and other mineral phases. Some geothermal power plants very successfully tested the application of sulfate scaling inhibitors. Here we present mineralogical analyses of scale samples from geothermal power plants in the Upper Rhine Valley deposited in absence and presence of sulfate scaling inhibitors. Solid samples are investigated using wet-chemistry (after digestion), XRPD, SEM-EDX, XPS, EA-IRMS, Raman spectroscopy, and XANES (for explanation of abbreviations, see main text). Samples of scales deposited in the absence of a sulfate scaling inhibitor mainly consist of two phases. The largest part is made up of a barite type (Ba,Sr,Ca)SO4 solid-solution. Traces of Ra occurring in the scaling are assumed to be incorporated in the barite type solid solution. Further minor phases are sulfide phases, either an Xray amorphous nano-particulate phase or galena (PbS). Since the application of the sulfate inhibitor, sulfate minerals are no longer detectable in the scale samples. Subsequent scalings are Pb-dominated and consist mainly of galena (PbS), elemental lead (Pb), arsenic (As) and antimony (Sb). As and Sb are likely present as a nanocrystalline intermetallic mixed compound ((Sb, As) or Pb3(Sb,As)2S3). The absence of barite-type minerals demonstrates the success of the application of the sulfate inhibitor. The precipitation of elemental Pb, As, and Sb, which are more noble than iron, may enhance the corrosion of mild steel pipes in the geothermal water circuit. Elution tests and oxidation of the scalings upon storage at atmospheric conditions demonstrate that proper disposal of the toxic heavy metal and metalloid containing scalings may be challenging

Continuous Adaptive Evolution of a Fast-Growing Corynebacterium glutamicum Strain Independent of Protocatechuate

Graf M, Haas T, Mueller F, et al. Continuous Adaptive Evolution of a Fast-Growing Corynebacterium glutamicum Strain Independent of Protocatechuate. Frontiers in Microbiology . 2019;10: 1648.Corynebacterium glutamicum is a commonly applied host for the industrial production of amino acids. While valued for its robustness, it is somewhat inferior to competing strains such as Escherichia coli because of the relatively low growth rate of 0.40 h(-1) in synthetic, industrial media. Accordingly, adaptive laboratory evolution (ALE) experiments were performed in continuous cultivation mode to select for a growth-improved host. To ensure industrial attractiveness, this ALE study aimed at a reduction of dependency on costly growth-boosting additives such as protocatechuate (RCA) or complex media supplements. Consequently, double selection pressures were installed consisting of a steady increase in growth rate demands and a parallel reduction of complex medium fractions. Selection yielded C. glutamicum EVO5 achieving 0.54 h(-1) and 1.03g(Glc) g(CDW)(-1) h(-1) in minimal medium without above mentioned supplements. Sequencing revealed 10 prominent mutations, three of them in key regulator genes

The SARS-coronavirus-host interactome

Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock

Low-level Circulation of Enterovirus D68–Associated Acute Respiratory Infections, Germany, 2014

We used physician sentinel surveillance to identify 25 (7.7%) mild to severe infections with enterovirus D68 (EV-D68) in children and adults among 325 outpatients with acute respiratory infections in Germany during August–October 2014. Results suggested low-level circulation of enterovirus D68 in Germany. Viruses were characterized by sequencing viral protein (VP) 1 and VP4/VP2 genomic regions