Comparison of electrophysiological and motility assays to study anthelmintic effects in Caenorhabditis elegans.

Currently, only a few chemical drug classes are available to control the global burden of nematode infections in humans and animals. Most of these drugs exert their anthelmintic activity by interacting with proteins such as ion channels, and the nematode neuromuscular system remains a promising target for novel intervention strategies. Many commonly-used phenotypic readouts such as motility provide only indirect insight into neuromuscular function and the site(s) of action of chemical compounds.

Anthelmintic drug actions in resistant and susceptible C. elegans revealed by electrophysiological recordings in a multichannel microfluidic device.

Many anthelmintic drugs used to treat parasitic nematode infections target proteins that regulate electrical activity of neurons and muscles: ion channels (ICs) and neurotransmitter receptors (NTRs). Perturbation of IC/NTR function disrupts worm behavior and can lead to paralysis, starvation, immune attack and expulsion. Limitations of current anthelmintics include a limited spectrum of activity across species and the threat of drug resistance, highlighting the need for new drugs for human and veterinary medicine.

Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing.

Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C.

Microfluidic platform for electrophysiological recordings from host-stage hookworm and Ascaris suum larvae: A new tool for anthelmintic research.

The screening of candidate compounds and natural products for anthelmintic activity is important for discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device ('chip') that records non-invasively the tiny electrophysiological signals generated by rhythmic contraction (pumping) of the worm's pharynx. These electropharyngeograms (EPGs) are recorded simultaneously from multiple worms per chip, providing a medium-throughput readout of muscular and neural activity that is especially useful for compounds targeting neurotransmitter receptors and ion channels.

Characterization of plasmids in extensively drug-resistant acinetobacter strains isolated in India and Pakistan.

The blaNDM-1 gene is associated with extensive drug resistance in Gram-negative bacteria. This probably spread to Enterobacteriaceae from Acinetobacter spp., and we characterized plasmids associated with blaNDM-1 in Acinetobacter spp.

Plasmid carriage of bla NDM-1 in clinical Acinetobacter baumannii isolates from India.

NDM-1 probably emerged in Acinetobacter species prior to its dissemination among Enterobacteriaceae, and NDM-1-like enzymes are increasingly reported in Acinetobacter species. Here, we report on the genetic context of blaNDM-1 in the earliest known NDM-1-producing organisms, clinical isolates of Acinetobacter from India in 2005. These strains harbor blaNDM-1 plasmids of different sizes.

A microfluidic device for whole-animal drug screening using electrophysiological measures in the nematode C. elegans.

This paper describes the fabrication and use of a microfluidic device for performing whole-animal chemical screens using non-invasive electrophysiological readouts of neuromuscular function in the nematode worm, C. elegans. The device consists of an array of microchannels to which electrodes are attached to form recording modules capable of detecting the electrical activity of the pharynx, a heart-like neuromuscular organ involved in feeding.

Steroid-triggered, cell-autonomous death of a Drosophila motoneuron during metamorphosis.

Background: The metamorphosis of Drosophila melanogaster is accompanied by elimination of obsolete neurons via programmed cell death (PCD). Metamorphosis is regulated by ecdysteroids, including 20-hydroxyecdysone (20E), but the roles and modes of action of hormones in regulating neuronal PCD are incompletely understood.

Results: We used targeted expression of GFP to track the fate of a larval motoneuron, RP2, in ventral ganglia.

Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study.

Background: Not all patients infected with NDM-1-positive bacteria have a history of hospital admission in India, and extended-spectrum β-lactamases are known to be circulating in the Indian community. We therefore measured the prevalence of the NDM-1 gene in drinking water and seepage samples in New Delhi.

Methods: Swabs absorbing about 100 μL of seepage water (ie, water pools in streets or rivulets) and 15 mL samples of public tap water were collected from sites within a 12 km radius of central New Delhi, with each site photographed and documented.

Emergence and persistence of integron structures harbouring VIM genes in the Children's Memorial Health Institute, Warsaw, Poland, 1998-2006.

Objectives: The aim was to perform a genetically detailed study of the emergence of metallo-beta-lactamase (MBL) genes in Pseudomonas spp. in the Children's Memorial Health Institute over a 9 year period.

Methods: Carbapenem-resistant Pseudomonas spp.

Segment-specific muscle degeneration is triggered directly by a steroid hormone during insect metamorphosis.

During metamorphosis of the hawkmoth, Manduca sexta, some larval muscles degenerate while others are respecified for new functions. In larvae, accessory planta retractor muscles (APRMs) are present in abdominal segments 1 to 6 (A1 to A6). APRMs serve as proleg retractors in A3 to A6 and body wall muscles in A1 and A2.

Thinking globally, acting locally: steroid hormone regulation of the dendritic architecture, synaptic connectivity and death of an individual neuron.

Steroid hormones act via evolutionarily conserved nuclear receptors to regulate neuronal phenotype during development, maturity and disease. Steroid hormones exert 'global' effects in organisms to produce coordinated physiological responses whereas, at the 'local' level, individual neurons can respond to a steroidal signal in highly specific ways. This review focuses on two phenomena-the loss of dendritic processes and the programmed cell death (PCD) of neurons-that can be regulated by steroid hormones (e.

Steroid-induced dendritic regression reduces anatomical contacts between neurons during synaptic weakening and the developmental loss of a behavior.

Steroid hormones alter dendritic architecture in many animals, but the exact relationship between dendritic anatomy, synaptic strength, and behavioral expression is typically unknown. In larvae of the moth Manduca sexta, the tip of each abdominal proleg (locomotory appendage) bears an array of mechanosensory hairs, each innervated by a planta hair sensory neuron (PH-SN). In the CNS, PH-SN axons make monosynaptic, excitatory nicotinic cholinergic connections with accessory planta retractor (APR) motoneurons.