Microfluidic electric parallel egg-laying assay and application to in-vivo toxicity screening of microplastics using C. elegans.

Environmental pollutants like microplastics are posing health concerns on aquatic animals and the ecosystem. Microplastic toxicity studies using Caenorhabditis elegans (C. elegans) as a model are evolving but methodologically hindered from obtaining statistically strong data sets, detecting toxicity effects based on microplastics uptake, and correlating physiological and behavioural effects at an individual-worm level.

Electric egg-laying: a new approach for regulating egg-laying behaviour in a microchannel using electric field.

In this paper, the novel effect of electric field (EF) on adult C. elegans egg-laying in a microchannel is discovered and correlated with neural and muscular activities. The quantitative effects of worm aging and EF strength, direction, and exposure duration on egg-laying are studied phenotypically using egg-count, body length, head movement, and transient neuronal activity readouts.

Parallel-Channel Electrotaxis and Neuron Screening of .

In this paper, we report a novel microfluidic method to conduct a electrotaxis movement assay and neuronal imaging on up to 16 worms in parallel. is a model organism for neurodegenerative disease and movement disorders such as Parkinson's disease (PD), and for screening chemicals that alleviate protein aggregation, neuronal death, and movement impairment in PD. Electrotaxis of in microfluidic channels has led to the development of neurobehavioral screening platforms, but enhancing the throughput of the electrotactic behavioral assay has remained a challenge.

The SEM-4 Transcription Factor Is Required for Regulation of the Oxidative Stress Response in .

Oxidative stress causes damage to cells by creating reactive oxygen species (ROS) and the overproduction of ROS have been linked to the onset of premature aging. We previously found that a (BRCA1 associated protein 2) mutant significantly increases the expression of phase II detoxification enzymes in An RNAi suppression screen to identify transcription factors involved in the production of mRNA in worms identified SEM-4 as a potential candidate. Here, we show that knockdown of suppresses the activation of caused by the mutation in We also demonstrate that required for survival upon exposure to oxidative stress and that SEM-4 is required for expression of the transcription factor SKN-1C.

The Oxidative Stress Response Requires the NHR-49 Transcription Factor.

The overproduction of reactive oxygen species (ROS) in cells can lead to the development of diseases associated with aging. We have previously shown that BRAP-2 (Brca1 associated binding protein 2) regulates phase II detoxification genes such as , by increasing SKN-1 activity. Previously, a transcription factor (TF) RNAi screen was conducted to identify potential activators that are required to induce expression in mutants.

BRAP-2 promotes DNA damage induced germline apoptosis in C. elegans through the regulation of SKN-1 and AKT-1.

As part of the DNA damage response (DDR) network, the tumour suppressor Breast cancer susceptibility gene 1 (BRCA1) is activated to facilitate DNA repair, transcription and cell cycle control. BRC-1, the Caenorhabditis elegans ortholog of BRCA1, has conserved function in DNA double strand break repair, wherein a loss of brc-1 results in high levels of germline apoptosis. BRAP2/IMP was initially identified as a BRCA1 associated binding protein and previously we have shown that the C.

The Oxidative Stress Response in Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2.

Cellular damage caused by reactive oxygen species is believed to be a major contributor to age-associated diseases. Previously, we characterized the Brap2 ortholog (BRAP-2) and found that it is required to prevent larval arrest in response to elevated levels of oxidative stress. Here, we report that mutants display increased expression of SKN-1-dependent, phase II detoxification enzymes that is dependent on PMK-1 (a p38 MAPK ortholog).

Loss of hif-1 promotes resistance to the exogenous mitochondrial stressor ethidium bromide in Caenorhabditis elegans.

Background: Mitochondrial dysfunction is one of the leading causes of neurological disorders in humans. Mitochondrial perturbations lead to adaptive mechanisms that include HIF-1 stabilization, though the consequences of increased levels of HIF-1 following mitochondrial stress remain poorly understood.

Results: Using Caenorhabditis elegans, we show that a hif-1 loss-of-function mutation confers resistance towards the mitochondrial toxin ethidium bromide (EtBr) and suppresses EtBr-induced production of ROS.

Caenorhabditis elegans wsp-1 regulation of synaptic function at the neuromuscular junction.

The Rho GTPase members and their effector proteins, such as the Wiskott-Aldrich syndrome protein (WASP), play critical roles in regulating actin dynamics that affect cell motility, endocytosis, cell division, and transport. It is well established that Caenorhabditis elegans wsp-1 plays an essential role in embryonic development. We were interested in the role of the C.

Developmental arrest of Caenorhabditis elegans BRAP-2 mutant exposed to oxidative stress is dependent on BRC-1.

Oxidative damage by reactive oxygen species is believed to be a contributor to the development of cancer and the physiological deterioration associated with aging. In this report, we describe the effect of reactive oxygen species exposure to a developing Caenorhabditis elegans organism containing a deletion in the homolog of BRCA1-associated protein 2 (BRAP-2). A mutant containing a deletion of brap-2 was highly sensitive to oxidizing conditions and demonstrated early larval arrest and lethality at low concentrations of the oxidative stress-inducing drug paraquat compared with the wild-type.

Lnk adaptor protein down-regulates specific Kit-induced signaling pathways in primary mast cells.

Stem cell factor (SCF) plays critical roles in proliferation, survival, migration, and function of hematopoietic progenitor and mast cells through binding to Kit receptor. Previous studies have implicated the adaptor protein Lnk as an important negative regulator of SCF signaling. However, the molecular mechanism underlying this regulation is unclear.

Functional analysis of the Caenorhabditis elegans UNC-73B PH domain demonstrates a role in activation of the Rac GTPase in vitro and axon guidance in vivo.

The Caenorhabditis elegans UNC-73B protein regulates axon guidance through its ability to act as a guanine nucleotide exchange factor (GEF) for the CeRAC/MIG-2 GTPases. Like other GEFs for Rho family GTPases, UNC-73B has a Dbl homology (DH) catalytic domain, followed by a C-terminal pleckstrin homology (PH) domain. We have explored whether the PH domain cooperates with the adjacent DH domain to promote UNC-73B GEF activity and axonal pathfinding.