Welsh-Bohmer KA, Lnenicka G, Corl AB, Page GP, Hirsch HV, Levin ED, Chen L, Kirshner A, Possidente D, Heberlein U, Possidente B, Aschner M, French R, Ruden D, Eddins D, Berger K, Linney E, Hayden KM, Helmcke K, Bartlett S
[
Neurotoxicology,
2009]
Considerable progress has been made over the past couple of decades concerning the molecular bases of neurobehavioral function and dysfunction. The field of neurobehavioral genetics is becoming mature. Genetic factors contributing to neurologic diseases such as Alzheimer's disease have been found and evidence for genetic factors contributing to other diseases such as schizophrenia and autism are likely. This genetic approach can also benefit the field of behavioral neurotoxicology. It is clear that there is substantial heterogeneity of response with behavioral impairments resulting from neurotoxicants. Many factors contribute to differential sensitivity, but it is likely that genetic variability plays a prominent role. Important discoveries concerning genetics and behavioral neurotoxicity are being made on a broad front from work with invertebrate and piscine mutant models to classic mouse knockout models and human epidemiologic studies of polymorphisms. Discovering genetic factors of susceptibility to neurobehavioral toxicity not only helps identify those at special risk, it also advances our understanding of the mechanisms by which toxicants impair neurobehavioral function in the larger population. This symposium organized by Edward Levin and Annette Kirshner, brought together researchers from the laboratories of Michael Aschner, Douglas Ruden, Ulrike Heberlein, Edward Levin and Kathleen Welsh-Bohmer conducting studies with Caenorhabditis elegans, Drosophila, fish, rodents and humans studies to determine the role of genetic factors in susceptibility to behavioral impairment from neurotoxic exposure.
[
Genetics,
2016]
The Genetics Society of America's Edward Novitski Prize recognizes an extraordinary level of creativity and intellectual ingenuity in the solution of significant problems in genetics research. The 2016 winner, Leonid Kruglyak, has made innovative contributions to the fields of linkage analysis, population genetics, and genomics, while drawing on a combination of mathematical, computational, and experimental approaches. Among other achievements, his work on statistical standards for genome-wide linkage studies has transformed their experimental design, and the linkage analysis program GENEHUNTER has been used to identify hundreds of human disease loci. Kruglyak's group also pioneered expression quantitative trait locus studies, which enabled variation in global gene expression to shed light on the genetics of complex human diseases. In recent years, his laboratory has focused on using genomic technology to establish Saccharomyces cerevisiae and Caenorhabditis elegans as model organisms for studies of complex genetic variation.
[
Plant Disease Reporter,
1975]
Twenty-five genera of nematodes were identified in six vegetable crops (carrot, pea, broccoli, rutabaga, Brussels sprouts, cauliflower) at fifty-six locations in Prince Edward Island (P.E.I.). Root lesion nematodes, Pratylenchus penetrans, were found in the soil at all locations and accounted for about 19% of the total nematode fauna. Meloidogyne hapla were recovered in only a few samples in low numbers, as were nematodes in the order Dorylaimida which accounted for about 5% of the total population. Non-stylet bearing nematodes made up 55% of the total and most of these were in two genera, Caenorhabditis spp. and Cephalobus spp. Carrot soils harbored the highest number of root lesion nematodes and pea soils had the least; 4726 and 547/kg of dry soil, respectively. Pea roots, however, had 2647/g dry root of these nematodes. No root lesion or other endoparasitic nematodes were recovered from the tap roots of carrots or from rutabagas. Some carrot and pea fields appeared to have lower than average yields where root lesion nematodes were recovered from soil and roots in very high numbers.
[
Methods Mol Biol,
2015]
Optogenetics was introduced as a new technology in the neurosciences about a decade ago (Zemelman et al., Neuron 33:15-22, 2002; Boyden et al., Nat Neurosci 8:1263-1268, 2005; Nagel et al., Curr Biol 15:2279-2284, 2005; Zemelman et al., Proc Natl Acad Sci USA 100:1352-1357, 2003). It combines optics, genetics, and bioengineering to render neurons sensitive to light, in order to achieve a precise, exogenous, and noninvasive control of membrane potential, intracellular signaling, network activity, or behavior (Rein and Deussing, Mol Genet Genomics 287:95-109, 2012; Yizhar et al., Neuron 71:9-34, 2011). As C. elegans is transparent, genetically amenable, has a small nervous system mapped with synapse resolution, and exhibits a rich behavioral repertoire, it is especially open to optogenetic methods (White et al., Philos Trans R Soc Lond B Biol Sci 314:1-340, 1986; De Bono et al., Optogenetic actuation, inhibition, modulation and readout for neuronal networks generating behavior in the nematode Caenorhabditis elegans, In: Hegemann P, Sigrist SJ (eds) Optogenetics, De Gruyter, Berlin, 2013; Husson et al., Biol Cell 105:235-250, 2013; Xu and Kim, Nat Rev Genet 12:793-801, 2011). Optogenetics, by now an "exploding" field, comprises a repertoire of different tools ranging from transgenically expressed photo-sensor proteins (Boyden et al., Nat Neurosci 8:1263-1268, 2005; Nagel et al., Curr Biol 15:2279-2284, 2005) or cascades (Zemelman et al., Neuron 33:15-22, 2002) to chemical biology approaches, using photochromic ligands of endogenous channels (Szobota et al., Neuron 54:535-545, 2007). Here, we will focus only on optogenetics utilizing microbial rhodopsins, as these are most easily and most widely applied in C. elegans. For other optogenetic tools, for example the photoactivated adenylyl cyclases (PACs, that drive neuronal activity by increasing synaptic vesicle priming, thus exaggerating rather than overriding the intrinsic activity of a neuron, as occurs with rhodopsins), we refer to other literature (Weissenberger et al., J Neurochem 116:616-625, 2011; Steuer Costa et al., Photoactivated adenylyl cyclases as optogenetic modulators of neuronal activity, In: Cambridge S (ed) Photswitching proteins, Springer, New York, 2014). In this chapter, we will give an overview of rhodopsin-based optogenetic tools, their properties and function, as well as their combination with genetically encoded indicators of neuronal activity. As there is not "the" single optogenetic experiment we could describe here, we will focus more on general concepts and "dos and don'ts" when designing an optogenetic experiment. We will also give some guidelines on which hardware to use, and then describe a typical example of an optogenetic experiment to analyze the function of the neuromuscular junction, and another application, which is Ca(2+) imaging in body wall muscle, with upstream neuronal excitation using optogenetic stimulation. To obtain a more general overview of optogenetics and optogenetic tools, we refer the reader to an extensive collection of review articles, and in particular to volume 1148 of this book series, "Photoswitching Proteins."