Saharan dust and ice nuclei over Central Europe

Surface measurements of aerosol and ice nuclei (IN) at a Central European mountain site during an episode of dust transport from the Sahara are presented. Ice nuclei were sampled by electrostatic precipitation on silicon wafers and were analyzed in an isothermal static vapor diffusion chamber. The transport of mineral dust is simulated by the Eulerian regional dust model DREAM. Ice nuclei and mineral dust are significantly correlated, in particular IN number concentration and aerosol surface area. The ice nucleating characteristics of the aerosol as analyzed with respect to temperature and supersaturation are similar during the dust episode than during the course of the year. This suggests that dust may be a main constituent of ice nucleating aerosols in Central Europe

Quantification of the novel N-methyl-D-aspartate receptor ligand [11C]GMOM in man

[11C]GMOM (carbon-11 labeled N-(2-chloro-5-thiomethylphenyl)-N0-(3-[11C]methoxy-phenyl)-N0-methylguanidine) is a PET ligand that binds to the N-methyl-D-aspartate receptor with high specificity and affinity. The purpose of this first in human study was to evaluate kinetics of [11C]GMOM in the healthy human brain and to identify the optimal pharmacokinetic model for quantifying these kinetics, both before and after a pharmacological dose of S-ketamine. Dynamic 90 min [11C]GMOM PET scans were obtained from 10 subjects. In six of the 10 subjects, a second PET scan was performed following an S-ketamine challenge. Metabolite corrected plasma input functions were obtained for all scans. Regional time activity curves were fitted to various single- and two-tissue compartment models. Best fits were obtained using a two-tissue irreversible model with blood volume parameter. The highest net influx rate (Ki) of [11C]GMOM was observed in regions with high N-methyl-D-aspartate receptor density, such as hippocampus and thalamus. A significant reduction in the Ki was observed for the entire brain after administration of ketamine, suggesting specific binding to the N-methyl-D-aspartate receptors. This initial study suggests that the [11C]GMOM could be used for quantification of N-methyl-D-aspartate receptors

Towards a standardized method for broth microdilution susceptibility testing of Haemophilus parasuis

Currently, there is no agreed method available for broth microdilution susceptibility testing of Haemophilus parasuis, one of the most important bacterial pathogens in pig production. Therefore, the aim of this study was to develop a method that could be easily performed by diagnostic laboratories and that appears suitable for a harmonized susceptibility testing. Growth determinations using one type strain and three field isolates revealed no visible growth of H. parasuis in media which have proven to be suitable for susceptibility testing of fastidious organisms. Therefore, a new medium, cation-adjusted Mueller-Hinton broth (CAMHB) plus NADH and sterile filtered heat-inactivated chicken serum, was developed. The reproducibility of MICs obtained in this medium was evaluated and statistically analyzed, considering a model with two different variables (precondition of five identical MICs and MIC mode accepting a deviation of ±1 dilution step, respectively). No significant differences for both variables were seen between two time points investigated and between results obtained with the recently proposed test medium broth (TMB). Nearly all MICs of quality control strains were in the acceptable range. Subsequently, 47 H. parasuis isolates representing 13 serovars were tested with the newly developed medium and TMB. Statistical analysis of all isolates and 15 antimicrobial agents and antimicrobial combinations showed no significant difference between MICs obtained in supplemented CAMHB and TMB. Because of a simplified implementation in routine diagnostic and a lower chance of interference between medium components and antimicrobial agents, supplemented CAMHB is recommended with an incubation time of 24 h

ProdoNet: identification and visualization of prokaryotic gene regulatory and metabolic networks

ProdoNet is a web-based application for the mapping of prokaryotic genes and the corresponding proteins to common gene regulatory and metabolic networks. For a given list of genes, the system detects shared operons, identifies co-expressed genes and deduces joint regulators. In addition, the contribution to shared metabolic pathways becomes visible on KEGG maps. Furthermore, the co-occurrence of genes of interest in gene expression profiles can be added to the visualization of the global network. In this way, ProdoNet provides the basis for functional genomics approaches and for the interpretation of transcriptomics and proteomics data. As an example, we present an investigation of an experimental membrane subproteome analysis of Pseudomonas aeruginosa with ProdoNet. The ProdoNet dataset on transcriptional regulation is based on the PRODORIC Prokaryotic Database of Gene Regulation and the Virtual Footprint tool. ProdoNet is accessible at http://www.prodonet.tu-bs.de

Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice

Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrPC, efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrPC selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrPSc and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories

The Human Minor Histocompatibility Antigen1 Is a RhoGAP

The human minor Histocompatibility Antigen HMHA-1 is a major target of immune responses after allogeneic stem cell transplantation applied for the treatment of leukemia and solid tumors. The restriction of its expression to hematopoietic cells and many solid tumors raised questions regarding its cellular functions. Sequence analysis of the HMHA-1 encoding HMHA1 protein revealed the presence of a possible C-terminal RhoGTPase Activating Protein (GAP) domain and an N-terminal BAR domain. Rho-family GTPases, including Rac1, Cdc42, and RhoA are key regulators of the actin cytoskeleton and control cell spreading and migration. RhoGTPase activity is under tight control as aberrant signaling can lead to pathology, including inflammation and cancer. Whereas Guanine nucleotide Exchange Factors (GEFs) mediate the exchange of GDP for GTP resulting in RhoGTPase activation, GAPs catalyze the low intrinsic GTPase activity of active RhoGTPases, resulting in inactivation. Here we identify the HMHA1 protein as a novel RhoGAP. We show that HMHA1 constructs, lacking the N-terminal region, negatively regulate the actin cytoskeleton as well as cell spreading. Furthermore, we show that HMHA1 regulates RhoGTPase activity in vitro and in vivo. Finally, we demonstrate that the HMHA1 N-terminal BAR domain is auto-inhibitory as HMHA1 mutants lacking this region, but not full-length HMHA1, showed GAP activity towards RhoGTPases. In conclusion, this study shows that HMHA1 acts as a RhoGAP to regulate GTPase activity, cytoskeletal remodeling and cell spreading, which are crucial functions in normal hematopoietic and cancer cells

Shiga Toxin-Mediated Hemolytic Uremic Syndrome: Time to Change the Diagnostic Paradigm?

Hemolytic uremic syndrome (HUS) is caused by enterohemorrhagic Escherichia coli (EHEC) which possess genes encoding Shiga toxin (stx), the major virulence factor, and adhesin intimin (eae). However, the frequency of stx-negative/eae-positive E. coli in stools of HUS patients and the clinical significance of such strains are unknown.Between 1996 and 2006, we sought stx-negative/eae-positive E. coli in stools of HUS patients using colony blot hybridization with the eae probe and compared the isolates to EHEC causing HUS. stx-negative/eae-positive E. coli were isolated as the only pathogens from stools of 43 (5.5%) of 787 HUS patients; additional 440 (55.9%) patients excreted EHEC. The majority (90.7%) of the stx-negative/eae-positive isolates belonged to serotypes O26:H11/NM (nonmotile), O103:H2/NM, O145:H28/NM, and O157:H7/NM, which were also the most frequent serotypes identified among EHEC. The stx-negative isolates shared non-stx virulence and fitness genes with EHEC of the corresponding serotypes and clustered with them into the same clonal complexes in multilocus sequence typing, demonstrating their close relatedness to EHEC.At the time of microbiological analysis, approximately 5% of HUS patients shed no longer the causative EHEC, but do excrete stx-negative derivatives of EHEC that lost stx during infection. In such patients, the EHEC etiology of HUS is missed using current methods detecting solely stx or Shiga toxin; this can hamper epidemiological investigations and lead to inappropriate clinical management. While maintaining the paradigm that HUS is triggered by Shiga toxin, our data demonstrate the necessity of considering genetic changes of the pathogen during infection to adapt appropriately diagnostic strategies

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Oxygen minimum zones in the eastern tropical Atlantic and Pacific oceans

Within the eastern tropical oceans of the Atlantic and Pacific basin vast oxygen minimum zones (OMZ) exist in the depth range between 100 and 900 m. Minimum oxygen values are reached at 300–500 m depth which in the eastern Pacific become suboxic (dissolved oxygen content <4.5 μmol kg−1) with dissolved oxygen concentration of less than 1 μmol kg−1. The OMZ of the eastern Atlantic is not suboxic and has relatively high oxygen minimum values of about 17 μmol kg−1 in the South Atlantic and more than 40 μmol kg−1 in the North Atlantic. About 20 (40%) of the North Pacific volume is occupied by an OMZ when using 45 μmol kg−1 (or 90 μmol kg−1, respectively) as an upper bound for OMZ oxygen concentration for ocean densities lighter than σθ < 27.2 kg m−3. The relative volumes reduce to less than half for the South Pacific (7% and 13%, respectively). The abundance of OMZs are considerably smaller (1% and 7%) for the South Atlantic and only ∼0% and 5% for the North Atlantic. Thermal domes characterized by upward displacements of isotherms located in the northeastern Pacific and Atlantic and in the southeastern Atlantic are co-located with the centres of the OMZs. They seem not to be directly involved in the generation of the OMZs. OMZs are a consequence of a combination of weak ocean ventilation, which supplies oxygen, and respiration, which consumes oxygen. Oxygen consumption can be approximated by the apparent oxygen utilization (AOU). However, AOU scaled with an appropriate consumption rate (aOUR) gives a time, the oxygen age. Here we derive oxygen ages using climatological AOU data and an empirical estimate of aOUR. Averaging oxygen ages for main thermocline isopycnals of the Atlantic and Pacific Ocean exhibit an exponential increase with density without an obvious signature of the OMZs. Oxygen supply originates from a surface outcrop area and can also be approximated by the turn-over time, the ratio of ocean volume to ventilating flux. The turn-over time corresponds well to the average oxygen ages for the well ventilated waters. However, in the density ranges of the suboxic OMZs the turn-over time substantially increases. This indicates that reduced ventilation in the outcrop is directly related to the existence of suboxic OMZs, but they are not obviously related to enhanced consumption indicated by the oxygen ages. The turn-over time suggests that the lower thermocline of the North Atlantic would be suboxic but at present this is compensated by the import of water from the well ventilated South Atlantic. The turn-over time approach itself is independent of details of ocean transport pathways. Instead the geographical location of the OMZ is to first order determined by: (i) the patterns of upwelling, either through Ekman or equatorial divergence, (ii) the regions of general sluggish horizontal transport at the eastern boundaries, and (iii) to a lesser extent to regions with high productivity as indicated through ocean colour data