Lomofungin,a New Antibiotic Produced by Streptomyces lomondensis sp. n

Lomofungin is a new antimicrobial agent obtained from the culture broth of Streptomyces lomondensis sp. n. UC-5022. Lomofungin is an acidic, olive-yellow, crystalline compound which inhibits, in vitro, a variety of pathogenic fungi, yeasts, and gram-positive and gram-negative bacteria.     

An evaluation of multidrug-resistant <Emphasis Type="Italic">Escherichia coli</Emphasis> isolates in urinary tract infections from Aguascalientes,Mexico: cross-sectional study

Background

Uropathogenic Escherichia coli (UPEC) are one of the main bacteria causing urinary tract infections (UTIs). The rates of UPEC with high resistance towards antibiotics and multidrug-resistant bacteria have increased dramatically in recent years and could difficult the treatment.

Methods

The aim of the study was to determine multidrug-resistant bacteria, antibiotic resistance profile, virulence traits, and genetic background of 110 E. coli isolated from community (79 isolates) and hospital-acquired (31 isolates) urinary tract infections. The plasmid-mediated quinolone resistance genes presence was also investigated. A subset of 18 isolates with a quinolone-resistance phenotype was examined for common virulence genes encoded in diarrheagenic and extra-intestinal pathogenic E. coli by a specific E. coli microarray.

Results

Female children were the group most affected by UTIs, which were mainly community-acquired. Resistance to trimethoprim–sulfamethoxazole, ampicillin, and ampicillin–sulbactam was most prevalent. A frequent occurrence of resistance toward ciprofloxacin (47.3%), levofloxacin (43.6%) and cephalosporins (27.6%) was observed. In addition, 63% of the strains were multidrug-resistant (MDR). Almost all the fluoroquinolone (FQ)-resistant strains showed MDR-phenotype. Isolates from male patients were associated to FQ-resistant and MDR-phenotype. Moreover, hospital-acquired infections were correlated to third generation cephalosporin and nitrofurantoin resistance and the presence of kpsMTII gene. Overall, fimH (71.8%) and fyuA (68.2%), had the highest prevalence as virulence genes among isolates. However, the profile of virulence genes displayed a great diversity, which included the presence of genes related to diarrheagenic E. coli. Out of 110 isolates, 25 isolates (22.7%) were positive to qnrA, 23 (20.9%) to qnrB, 7 (6.4%) to qnrS1, 7 (6.4%) to aac(6′)lb-cr, 5 (4.5%) to qnrD, and 1 (0.9%) to qnrC genes. A total of 12.7% of the isolates harbored bla_CTX-M genes, with bla_CTX-M-15 being the most prevalent.

Conclusions

Urinary tract infection due to E. coli may be difficult to treat empirically due to high resistance to commonly used antibiotics. Continuous surveillance of multidrug resistant organisms and patterns of drug resistance are needed in order to prevent treatment failure and reduce selective pressure. These findings may help choosing more suitable treatments of UTI patients in this region of Mexico.

     

The Pericyte of the Pancreatic Islet Regulates Capillary Diameter and Local Blood Flow

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Profilin Negatively Regulates Formin-Mediated Actin Assembly to Modulate PAMP-Triggered Plant Immunity

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Physiological Concentrations of Zinc Have Dual Effects on P2X Myenteric Receptors of Guinea Pig

We, hereby, characterize the pharmacological effects of physiological concentrations of Zinc on native myenteric P2X receptors from guinea-pig small intestine and on P2X2 isoforms present in most myenteric neurons. This is the first study describing opposite effects of Zinc on these P2X receptors. It was not possible to determine whether both effects were concentration dependent, yet the inhibitory effect was mediated by competitive antagonism and was concentration dependent. The potentiating effect appears to be mediated by allosteric changes induced by Zinc on P2X myenteric channels, which is more frequently observed in myenteric neurons with low zinc concentrations. In P2X2-1 and P2X2-2 variants, the inhibitory effect is more common than in P2X myenteric channels. However, in the variants, the potentiatory effect is of equal magnitude as the inhibitory effect. Inhibitory and potentiatory effects are likely mediated by different binding sites that appear to be present on both P2X2 variants. In conclusion, in myenteric native P2X receptors, Zinc has quantitatively different pharmacological effects compared to those observed on homomeric channels: P2X2-1 and P2X2-2. Potentiatory and inhibitory Zinc effects upon these receptors are mediated by two different binding sites. All our data suggest that myenteric P2X receptors have a more complex pharmacology than those of the recombinant P2X2 receptors, which is likely related to other subunits known to be expressed in myenteric neurons. Because these dual effects occur at Zinc physiological concentrations, we suggest that they could be involved in physiological and pathological processes.     

Characterization of a Human Serum Inhibitor of Clostridium histolyticum Proteinase(s)

Normal animal sera inhibit at least one Clostridium histolyticum proteinase. An assay procedure based on immune hemolysis was developed for the estimation of this inhibition. This inhibitory activity occurs in various levels in the sera of different animal species. The highest titers have been obtained with rat sera. The inhibitory activity from human serum was isolated and purified 16- to 27-fold by Sephadex G-200 gel filtration and diethylaminoethyl cellulose or hydroxylapatite chromatography. The properties of the human serum inhibitor of the clostridial proteinase were compared with a trypsin inhibiting factor found in the partially purified preparations. Identical behavior of the two inhibitory factors was observed when measured by heat inactivation, beta-mercaptoethanol sensitivity, pH stability, and sucrose gradient centrifugation. The inhibitory factor has an approximate sedimentation coefficient (S(20,w)) of 17. Goat anti-alpha-2-macroglobulin specifically precipitated the clostridial proteinase inhibitor from a partially purified preparation.     

Global genetic diversity of Aedes aegypti

Mosquitoes, especially Aedes aegypti, are becoming important models for studying invasion biology. We characterized genetic variation at 12 microsatellite loci in 79 populations of Ae. aegypti from 30 countries in six continents, and used them to infer historical and modern patterns of invasion. Our results support the two subspecies Ae. aegypti formosus and Ae. aegypti aegypti as genetically distinct units. Ae. aegypti aegypti populations outside Africa are derived from ancestral African populations and are monophyletic. The two subspecies co‐occur in both East Africa (Kenya) and West Africa (Senegal). In rural/forest settings (Rabai District of Kenya), the two subspecies remain genetically distinct, whereas in urban settings, they introgress freely. Populations outside Africa are highly genetically structured likely due to a combination of recent founder effects, discrete discontinuous habitats and low migration rates. Ancestral populations in sub‐Saharan Africa are less genetically structured, as are the populations in Asia. Introduction of Ae. aegypti to the New World coinciding with trans‐Atlantic shipping in the 16th to 18th centuries was followed by its introduction to Asia in the late 19th century from the New World or from now extinct populations in the Mediterranean Basin. Aedes mascarensis is a genetically distinct sister species to Ae. aegypti s.l. This study provides a reference database of genetic diversity that can be used to determine the likely origin of new introductions that occur regularly for this invasive species. The genetic uniqueness of many populations and regions has important implications for attempts to control Ae. aegypti, especially for the methods using genetic modification of populations.     

Scheduling data analytics work with performance guarantees: queuing and machine learning models in synergy

In today’s scaled out systems, co-scheduling data analytics work with high priority user workloads is common as it utilizes better the vast hardware availability. User workloads are dominated by periodic patterns, with alternating periods of high and low utilization, creating promising conditions to schedule data analytics work during low activity periods. To this end, we show the effectiveness of machine learning models in accurately predicting user workload intensities, essentially by suggesting the most opportune time to co-schedule data analytics work. Yet, machine learning models cannot predict the effects of performance interference when co-scheduling is employed, as this constitutes a “new” observation. Specifically, in tiered storage systems, their hierarchical design makes performance interference even more complex, thus accurate performance prediction is more challenging. Here, we quantify the unknown performance effects of workload co-scheduling by enhancing machine learning models with queuing theory ones to develop a hybrid approach that can accurately predict performance and guide scheduling decisions in a tiered storage system. Using traces from commercial systems we illustrate that queuing theory and machine learning models can be used in synergy to surpass their respective weaknesses and deliver robust co-scheduling solutions that achieve high performance.     

Defining nicotinic agonist binding surfaces through photoaffinity labeling

Nicotinic acetylcholine (ACh) receptor (nAChR) agonists are potential therapeutic agents for neurological dysfunction. In the present study, the homopentameric mollusk ACh binding protein (AChBP), used as a surrogate for the extracellular ligand-binding domain of the nAChR, was specifically derivatized by the highly potent agonist azidoepibatidine (AzEPI) prepared as a photoaffinity probe and radioligand. One EPI-nitrene photoactivated molecule was incorporated in each subunit interface binding site based on analysis of the intact derivatized protein. Tryptic fragments of the modified AChBP were analyzed by collision-induced dissociation and Edman sequencing of radiolabeled peptides. Each specific EPI-nitrene-modified site involved either Tyr195 of loop C on the principal or (+)-face or Met116 of loop E on the complementary or (-)-face. The two derivatization sites were observed in similar frequency, providing evidence of the reactivity of the azido/nitrene probe substituent and close proximity to both residues. [3H]AzEPI binds to the alpha4beta2 nAChR at a single high-affinity site and photoaffinity-labels only the alpha4 subunit, presumably modifying Tyr225 spatially corresponding to Tyr195 of AChBP. Phe137 of the beta2 nAChR subunit, equivalent to Met116 of AChBP, conceivably lacks sufficient reactivity with the nitrene generated from the probe. The present photoaffinity labeling in a physiologically relevant condition combined with the crystal structure of AChBP allows development of precise structural models for the AzEPI interactions with AChBP and alpha4beta2 nAChR. These findings enabled us to use AChBP as a structural surrogate to define the nAChR agonist site.     

Insights into a novel three-partner interaction between ants,coreids (Hemiptera: Coreidae) and extrafloral nectaries: implications for the study of protective mutualisms

Extrafloral nectar of plants and honeydew of hemipterans are the common mediators of facultative interactions that involve ants as a mobile strategy of defence. The outcome of these interactions can vary from mutualistic to commensalistic or even antagonistic, depending on the ecological context and the interacting species. Here, we explore a novel, three-partner interaction involving ants, the coreid Dersagrena subfoveolata (Hemiptera) and the extrafloral nectaries (EFNs) bearing plant Senna aphylla (Fabaceae) in semi-arid Northwest Argentina. We surveyed natural areas and conducted ant exclusion experiments, to understand how each pairwise interaction influences the overall outcome among the three interacting parts. The outcome of the interactions was assessed for experimental plants as the reproductive output and herbivore abundances and for coreids as predator abundances. We found that the coreids occurred exclusively on S. aphylla plants and that at least nine ant species interacted with the EFNs as well as with the coreids. Coreid occurrence and abundance depended on ant densities, which in turn, was determined by the presence of actively secreting EFNs. Coreid and ant presence did not influence plant reproductive success, and ants provided to coreids some biotic defence, mainly against vespid wasp predators, but had no effect on non-coreid herbivores. We conclude that the interaction outcome is commensalistic between ants and plants (assuming that EF nectar is not costly for the plant), antagonistic between coreids and plants, and mutualistic between coreids and ants. The sum of all outcomes is net positive effect for ants and coreids, and net slightly negative to neutral for plants.