Bacterial conjugation constitutes a major horizontal gene transfer mechanism for the dissemination of antibiotic resistance genes among human pathogens. Antibiotic resistance spread could be halted or diminished by molecules that interfere with the conjugation process. In this work, synthetic 2-alkynoic fatty acids were identified as a novel class of conjugation inhibitors. Their chemical properties were investigated by using the prototype 2-hexadecynoic acid and its derivatives. Essential features of effective inhibitors were the carboxylic group, an optimal long aliphatic chain of 16 carbon atoms, and one unsaturation. Chemical modification of these groups led to inactive or less-active derivatives. Conjugation inhibitors were found to act on the donor cell, affecting a wide number of pathogenic bacterial hosts, including Escherichia, Salmonella, Pseudomonas, and Acinetobacter spp. Conjugation inhibitors were active in inhibiting transfer of IncF, IncW, and IncH plasmids, moderately active against IncI, IncL/M, and IncX plasmids, and inactive against IncP and IncN plasmids. Importantly, the use of 2-hexadecynoic acid avoided the spread of a derepressed IncF plasmid into a recipient population, demonstrating the feasibility of abolishing the dissemination of antimicrobial resistances by blocking bacterial conjugation.
Neuromorphic engineers study models and implementations of systems that mimic neurons behavior in the brain. Neuro-inspired systems commonly use spikes to represent information. This representation has several advantages: its robustness to noise thanks to repetition, its continuous and analog information representation using digital pulses, its capacity of pre-processing during transmission time, ... , Furthermore, spikes is an efficient way, found by nature, to codify, transmit and process information. In this paper we propose, design, and analyze neuro-inspired building blocks that can perform spike-based analog filters used in signalprocessing. We present a VHDL implementation for FPGA.Presented building blocks take advantages of the spike rate coded representation to perform a massively parallel processing without complex hardware units, like floating point arithmetic units, or a large memory. Those low requirements of hardware allow the integration of a high number of blocks inside a FPGA, allowing to process fully in parallel several spikes coded signals.
A very expedient and efficient new route toward taiwaniaquinoids, bearing the 4a-methyltetrahydrofluorene skeleton, is reported. Key steps are the intramolecular Friedel-Crafts alkylation of an aryldiene and the degradative oxidation of a methylenedioxy group; the latter process could also be utilized for building the 2-hydroxy-1,4-benzoquinone unit, which is frequently found in natural products. Utilizing this new methodology, (+/-)-dichroanone (7) (three steps, 77% overall yield) and (+/-)-taiwaniaquinone H (6) (four steps, 70% overall yield) have been synthesized from commercial alpha- (11a) or beta-cyclocitral (11b).
Bacterial conjugation is the main mechanism for the dissemination of multiple antibiotic resistance in human pathogens. This dissemination could be controlled by molecules that interfere with the conjugation process. A search for conjugation inhibitors among a collection of 1,632 natural compounds, identified tanzawaic acids A and B as best hits. They specially inhibited IncW and IncFII conjugative systems, including plasmids mobilized by them. Plasmids belonging to IncFI, IncI, IncL/M, IncX and IncH incompatibility groups were targeted to a lesser extent, whereas IncN and IncP plasmids were unaffected. Tanzawaic acids showed reduced toxicity in bacterial, fungal or human cells, when compared to synthetic conjugation inhibitors, opening the possibility of their deployment in complex environments, including natural settings relevant for antibiotic resistance dissemination.
For a given measurable space (Ω, Σ), and a vector measure m : Σ −→ X with values in a Banach space X we consider the spaces of p-power integrable and weakly integrable, respectively, functions with respect to the measure m, L p (m) and L p w (m), for 1 p < ∞.In this note we describe the real interpolated spaces that we obtain when the K -method is applied to any couple of these spaces.
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