Agro-economic evaluation of fertilizer recommendations for rainfed lowland rice

Abstract not availableS.M. Haefele, N. Sipaseuth, V. Phengsouvanna, K. Dounphady, S. Vongsouth

Novel HldE‑K Inhibitors Leading to Attenuated Gram Negative Bacterial Virulence

We report here the optimization of an HldE kinase inhibitor to low nanomolar potency, which resulted in the identification of the first reported compounds active on selected <i>E. coli</i> strains. One of the most interesting candidates, compound <b>86</b>, was shown to inhibit specifically bacterial LPS heptosylation on efflux pump deleted <i>E. coli</i> strains. This compound did not interfere with <i>E. coli</i> bacterial growth (MIC > 32 μg/mL) but sensitized this pathogen to hydrophobic antibiotics like macrolides normally inactive on Gram-negative bacteria. In addition, <b>86</b> could sensitize <i>E. coli</i> to serum complement killing. These results demonstrate that HldE kinase is a suitable target for drug discovery. They also pave the way toward novel possibilities of treating or preventing bloodstream infections caused by pathogenic Gram negative bacteria by inhibiting specific virulence factors

Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS

Fluorescent sensors are an essential part of the experimental toolbox of the life sciences, where they are used ubiquitously to visualize intra- and extracellular signaling. In the brain, optical neurotransmitter sensors can shed light on temporal and spatial aspects of signal transmission by directly observing, for instance, neurotransmitter release and spread. Here we report the development and application of the first optical sensor for the amino acid glycine, which is both an inhibitory neurotransmitter and a co-agonist of the N-methyl-d-aspartate receptors (NMDARs) involved in synaptic plasticity. Computational design of a glycine-specific binding protein allowed us to produce the optical glycine FRET sensor (GlyFS), which can be used with single and two-photon excitation fluorescence microscopy. We took advantage of this newly developed sensor to test predictions about the uneven spatial distribution of glycine in extracellular space and to demonstrate that extracellular glycine levels are controlled by plasticity-inducing stimuli

The MUT056399 Inhibitor of FabI Is a New Antistaphylococcal Compound▿

MUT056399 is a highly potent new inhibitor of the FabI enzyme of both Staphylococcus aureus and Escherichia coli. In vitro, MUT056399 was very active against S. aureus strains, including methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), linezolid-resistant, and multidrug-resistant strains, with MIC90s between 0.03 and 0.12 μg/ml. MUT056399 was also active against coagulase-negative staphylococci, with MIC90s between 0.12 and 4 μg/ml. The antibacterial spectrum is consistent with specific FabI inhibition with no activity against bacteria using FabK but activity against FabI-containing Gram-negative bacilli. In vitro, resistant clones of S. aureus were obtained at a low frequency. All of the resistant clones analyzed were found to contain mutations in the fabI gene. In vivo, MUT056399, administered subcutaneously, protected mice from a lethal systemic infection induced by MSSA, MRSA, and vancomycin-intermediate S. aureus strains (50% effective doses ranging from 19.3 mg/kg/day to 49.6 mg/kg/day). In the nonneutropenic murine thigh infection model, the same treatment with MUT056399 reduced the bacterial multiplication of MSSA and MRSA in the thighs of immunocompetent mice. These properties support MUT056399 as a very promising candidate for a novel drug to treat severe staphylococcal infections

Supportive strategies to improve adherence to IFN β-1b in multiple sclerosis - Results of the βPlus observational cohort study.

BACKGROUND: Low adherence to treatment in Multiple Sclerosis (MS) has been shown to lead to poor health outcomes. Various strategies to improve adherence have been suggested including educative programs, injection devices and dedicated nurse assistance. OBJECTIVE: To assess the impact of elements of the patient support program on adherence; to explore disease factors affecting adherence; and to determine whether these factors influence the choices of supportive elements. METHODS: A prospective, observational cohort study was conducted. MS patients were eligible if they had switched to Interferon beta-1b (IFNB-1b) between 1 and 3 months prior to inclusion. Data were collected at months 6, 12, 18 and 24 after inclusion. Adherence was defined as completion of both study protocol and medication at 24 months. Patients underwent evaluations of disability, quality of life, depression, and coping styles. RESULTS: A total of 1077 patients from 15 countries were included, of which 61.8% were adherent to IFNB-1b after 24-months. Depression, quality of life and autoinjector devices were baseline predictors of adherence at 24-months. Coping styles did not show to have substantial impact on adherence. Lower quality of life increased the probability of choosing supportive elements. CONCLUSION: The study showed that the usage of autoinjector devices chosen during the study was the strongest predictor of drug adherence of all the supportive elements tested in this study