Miller MJ (1980) Drugs "Use of levamisole in parasitic infections."

Miller MJ

[Drugs, 1980]

Levamisole is a drug of choice for treatment of ascariasis. With recommended dosages, it is virtually free of side effects. Single doses of 50 to 150mg will eliminate all parasites in 90 to 100% of ascariasis patients irrespective of worm burden. Activity against hookworms has been demonstrated for levamisole but the most effective treatment regimen has not been determined. Further drug trials are needed for better assessment of efficacy. Levamisole has little or no curative action on infections with whipworms and pinworms. It may have some activity against strongyloides but confirmatory studies are needed. It has been shown that levamisole has significant activity against microfilariae of Wuchereria bancrofti and Brugia malayi. It is not, however, as effective as diethylcarbamazine ('Hetrazan'), and side reactions are greater. In tolerated doses, levamisole does not have significant action on adult forms or microfilariae of Onchoceea volvulus. The drug applied topically, however, may find a place in treatment of ocular onchocerciasis. Limited trials with levamisole for toxoplasmosis and chronic cutaneous leishmaniasis have given promising results, and further studies are indicated.

Miller DM et al. (1992) Worm Breeder's Gazette "unc-4 LacZ Expression in A-Type Motor Neurons"

Miller DM, Niemeyer CJ

[Worm Breeder's Gazette, 1992]

unc-4 LacZ expression in A-type motor neurons David M. Miller and Charles J. Niemeyer, Dept. of Cell Biology, Duke Univ. Medical Ctr, Durham, NC 27710

Johnson, Christina K. et al. (2021) MicroPubl Biol

Miller III, David M., Johnson, Christina K., Bianchi, Laura

[MicroPubl Biol, 2021]

For Johnson, CK; Miller, DD; Bianchi, L (2021). Effect of the protease plasmin on C. elegans hyperactive DEG/ENaC channels MEC-4(d) and UNC-8(d). microPublication Biology. 10.17912/micropub.biology.000412.

Bichai F et al. (2009) Water Res "Protection against UV disinfection of E. coli bacteria and B. subtilis spores ingested by C. elegans nematodes."

Barbeau B, Bichai F, Payment P

[Water Res, 2009]

Nematodes, which occur abundantly in granular media filters of drinking water treatment plants and in distribution systems, can ingest and transport pathogenic bacteria and provide them protection against chemical disinfectants. However, protection against UV disinfection had not been investigated to date. In this study, Caenorhabditis elegans nematodes (wild-type strain N2) were allowed to feed on Escherichia coli OP50 and Bacillus subtilis spores before being exposed to 5 and 40 mJ/cm(2) UV fluences, using a collimated beam apparatus (LP, 254 nm). Sonication (15 W, 60s) was used to extract bacteria from nematode guts following UV exposure in order to assess the amount of ingested bacteria that resisted the UV treatment using a standard culture method. Bacteria located inside the gut of C. elegans were shown to benefit from a significant protection against UV. Approximately 15% of the applied UV fluence of 40 mJ/cm(2) (as typically used in WTP) was found to reach the bacteria located inside nematode guts based on the inactivation of recovered bacteria (2.7 log reduction of E. coli bacteria and 0.7 log reduction of B. subtilis spores at 40 mJ/cm(2)). To our knowledge, this study is the first demonstration of the protection effect of bacterial internalization by higher organisms against UV treatment, using the specific case of E. coli and B. subtilis spores ingested by C. elegans.

Siavash Karimzadegan et al. (2007) International Worm Meeting "A mutagenesis screen for genes involved in deactivating the unc-4 transcription factor."

Victor Chiang, Martin Chalfie, Siavash Karimzadegan

[International Worm Meeting, 2007]

Transcriptional activators are often modulated and eventually turned off after their initial activation. While many studies have investigated transcription factor activation pathways, relatively less attention has been paid to the deactivation of these molecules. [Kodadek et al. (2006) Cell 127: 261-264]. Using a short-lived GFP driven by the unc-4 promoter, we have examined the inactivation of this transcription factor. UNC-4 is a homeodomain protein [Miller et al. (1992) Nature 355: 841-845] that is expressed in A-type motorneurons and appears to specify their differentiation including their synaptic partners. Northern blots indicate that peak unc-4 mRNA transcript levels occur at late L1/early L2 [Miller et al. (1995) Development 121: 2877-2886], concurrent with the developmental stage when A-type motorneurons receive synaptic input from interneurons [Miller et al. (1992) Nature 355: 841-845]. Thereafter, transcript levels fall precipitously, and adults no longer express unc-4 mRNA. Similarly, strains carrying unstable GFP driven by the unc-4 promoter produce GFP label in A-type motorneurons only at this L1/L2 stage. [Zhang et al. (2004) Cell 119(1): 137-44; Poyurovsky et al. (2004) Mol Cell 12(4): 875-87]. We have used this strain to screen for mutants in order to identify candidates where the unc-4 promoter is constitutively active beyond the L1/L2 stage. A screen of 22,000 haploid genomes yielded 12 candidates where GFP fluorescence is observed in all A-type motorneurons during adult stage. A further 19 candidates showed GFP fluorescence in a subset of the A-type motorneuron during adult stage. Complementation and mapping are in progress to identify these candidates.

Kuwabara PE (2003) Genes Dev "The multifaceted C. elegans major sperm protein: an ephrin signaling antagonist in oocyte maturation."

Kuwabara PE

[Genes Dev, 2003]

In sexually reproducing animals, the ability to coordinate oocyte maturation and sperm availability has profound effects on reproductive success. In Caenorhabditis elegans, cell-cell signaling is crucial for promoting germline development, oocyte maturation, and ovulation. In this issue of Genes & Development, Miller et al. (2003) provide new insights into the role that sperm play in oocyte maturation and ovulation. Even before sperm and oocyte have the opportunity to meet, sperm establish their presence by signaling to oocytes and the somatic gonad. In turn, oocytes respond by resuming meiotic cell cycle progression and preparing for fertilization.

Corey A Morris et al. (2003) International Worm Meeting "Site-directed mutagenesis of the transcription factor LIN-31 reveals functional domains required in the regulation of vulval cell fates."

David B Doroquez, E Lorena Mora-Blanco, Leilani M Miller, Yvonne Yang, Corey A Morris

[International Worm Meeting, 2003]

In order to better understand cell fate determination in Caenorhabditis elegans, we are conducting a functional analysis of LIN-31, a winged-helix transcription factor (WH TF) that acts as a tissue-specific effector of the conserved Ras/MAP kinase signaling pathway to promote or suppress vulval cell fates in the development of the hermaphrodite vulva (Miller et al., Genes and Dev., 7:933, 1993). In addition to a DNA-binding domain (DBD), the LIN-31 protein contains several regions of interest: a small acidic-rich region, four MAP kinase consensus phosphorylation sites, and a small region at the C-terminus that displays homology with a subset of WH proteins. These regions could play a number of roles, from transcriptional activation to an interaction domain for LIN-1, which is known to heterodimerize with LIN-31 (Tan et al., Cell, 93:569,1998). Using site-directed mutagenesis techniques, specific mutations were introduced into the gene at these regions of interest. Stable transgenic lines were created through germline microinjection of mutant plasmids into animals with no functional LIN-31. Through phenotypic analysis of multiple transgenic lines, we are beginning to better understand the functional significance and contribution of each of these different sites to LIN-31 function. Our results thus far support the current model (Miller et al., 1993; Tan et al., 1998; Miller et al., Genetics, 156:1595, 2000), that LIN-31 has two functions: 1) to activate vulval cell fates in P5.p, P6.p and P7.p; and 2) to repress vulval cell fates in P3.p, P4.p, and P8.p.In addition, we are initiating an in vitro functional analysis of LIN-31 protein. We used a bacterial expression system to produce GST::LIN-31 fusion protein. Using electrophoretic mobility shift assays, we have determined that wild-type LIN-31 protein is able to specifically bind the promoter of another WH TF target. LIN-31's ability to interact with this promoter was disrupted when 1) LIN-31 carried a previously characterized point mutation in the DBD believed to disrupt its interaction with the target DNA (Miller et al., 2000) and 2) when the promoter sequence contained base substitutions. We are now in the process of creating, expressing, and purifying mutant GST::LIN-31 fusion proteins in order to investigate LIN-31 sequences required for heterodimerization with LIN-1.

Miller KG et al. (1999) Neuron "Goalpha and diacylglycerol kinase negatively regulate the Gqalpha pathway in C. elegans."

Emerson MD, Rand JB, Miller KG

[Neuron, 1999]

We investigated the EGL-30 (Gqalpha) pathway in C. elegans by using genetic screens to identify genes that confer phenotypes similar to egl-30 mutants. One such gene, egl-8, encodes a phospholipase Cbeta that is present throughout the nervous system and near intestinal cell junctions. EGL-30 and EGL-8 appear to positively regulate synaptic transmission because reducing their function results in strong aldicarb resistance and slow locomotion rates. In contrast, GOA-1 (Goalpha) and DGK-1 (diacylglycerol kinase) appear to negatively regulate synaptic transmission, because reducing their function results in strong aldicarb hypersensitivity and hyperactive locomotion. A genetic analysis suggests that GOA-1 negatively regulates the EGL-30 pathway and that DGK-1 antagonizes the EGL-30 pathway.AD - Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.FAU - Miller, K GAU - Miller KGFAU - Emerson, M DAU - Emerson MDFAU - Rand, J BAU - Rand JBLA - engSI - GENBANK/AF179426ID - NS33187/NS/NINDSPT - Journal ArticleCY - UNITED STATESTA - NeuronJID - 8809320RN - 0 (Helminth Proteins)RN - 0 (Isoenzymes)RN - 0 (guanine nucleotide-binding protein Go)RN - EC 2.7.1.107 (Diacylglycerol Kinase)RN - EC 3.1.4.- (phospholipase C beta)RN - EC 3.1.4.3 (Phospholipase C)RN - EC 3.6.1.- (Heterotrimeric GTP-Binding Proteins)SB - IM

Miller MA et al. (2001) Science "A sperm cytoskeletal protein that signals oocyte meiotic maturation and ovulation."

Schedl TB, Kosinski ME, Miller MA, Lee MH, Greenstein D, Caprioli RM, Nguyen VQ

[Science, 2001]

Caenorhabditis elegans oocytes, like those of most animals, arrest during meiotic prophase. Sperm promote the resumption of meiosis (maturation) and contraction of smooth muscle-like gonadal sheath cells, which are required for ovulation. We show that the major sperm cytoskeletal protein (MSP) is a bipartite signal for oocyte maturation and sheath contraction. MSP also functions in sperm locomotion, playing a role analogous to actin. Thus, during evolution, MSP has acquired extracellular signaling and intracellular cytoskeletal functions for reproduction. Proteins with MSP-like domains are found in plants, fungi, and other animals, suggesting that related signaling functions may exist in other phyla.AD - Department of Cell Biology, Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.FAU - Miller, M AAU - Miller MAFAU - Nguyen, V QAU - Nguyen VQFAU - Lee, M HAU - Lee MHFAU - Kosinski, MAU - Kosinski MFAU - Schedl, TAU - Schedl TFAU - Caprioli, R MAU - Caprioli RMFAU - Greenstein, DAU - Greenstein DLA - engID - CA09592/CA/NCIID - GM57173/GM/NIGMSID - GM58008/GM/NIGMSID - HD07043/HD/NICHDID - HD25614/HD/NICHDPT - Journal ArticleCY - United StatesTA - ScienceJID - 0404511RN - 0 (Carrier Proteins)RN - 0 (Helminth Proteins)RN - 0 (MAP Kinase Signaling System)RN - 0 (Membrane Proteins)RN - 0 (Recombinant Proteins)RN - 0 (VAP-33 protein)RN - 0 (major sperm protein, nematode)RN - EC 2.7.1.- (Mitogen-Activated Protein Kinases)SB - IM

Corey A Morris et al. (2002) West Coast Worm Meeting "SITE-DIRECTED MUTANTS OF THE C. elegans TRANSCRIPTION FACTOR LIN-31 REVEAL DISTINCT FUNCTIONS."

Corey A Morris, E Lorena Mora-Blanco, Yvonne Yang, David B Doroquez, Leilani M Miller

[West Coast Worm Meeting, 2002]

In order to better understand cell fate determination in Caenorhabditis elegans, we are conducting a functional analysis of LIN-31, a winged-helix transcription factor (WH TF) that acts as a tissue-specific effector of the conserved Ras/MAP kinase signaling pathway to promote or suppress vulval cell fates in the development of the hermaphrodite vulva (Miller et al., Genes and Dev., 7:933, 1993). In addition to a DNA-binding domain (DBD), the LIN-31 protein contains several regions of interest: a small acidic-rich region, four MAP kinase consensus phosphorylation sites, and a small region at the C-terminus that displays homology with a subset of WH proteins. These regions could play a number of roles, from transcriptional activation to an interaction domain for LIN-1, which is known to heterodimerize with LIN-31 (Tan et al., Cell, 93:569,1998). Using site-directed mutagenesis techniques, specific mutations were introduced into the gene at these regions of interest. Stable transgenic lines were created through germline microinjection of mutant plasmids into animals with no functional LIN-31 protein. Through phenotypic analysis of multiple transgenic lines, we are beginning to better understand the functional significance and contribution of each of these different sites to LIN-31 function. Our results thus far support the current model (Miller et al., 1993; Tan et al., 1998; Miller et al., Genetics, 156:1595, 2000), that LIN-31 has two functions: 1) to activate vulval cell fates in P5.p, P6.p and P7.p; and 2) to repress vulval cell fates in P3.p, P4.p, and P8.p. In addition, we are initiating a functional analysis of LIN-31 protein using two assays: ability to bind a putative DNA target sequence and ability to heterodimerize with LIN-1. We used a bacterial expression system to produce GST::LIN-31 fusion protein. Using gel-shift assays, we confirmed function of wild-type protein by demonstrating its ability to bind the transthyretin (TTR) promoter, a consensus sequence recognized by HNF-3, another WH TF sharing DBD sequence homology (Costa et al., Mol. Cell. Biol., 9:1415, 1989). We are now in the process of creating, expressing, and purifying GST::LIN-31 fusion proteins carrying specific mutations, including two point mutations in the DBD believed to disrupt interaction of the LIN-31 with its target DNA (Miller et al., 2000). These mutant proteins will allow us to test in vitro their ability to bind the TTR promoter and to heterodimerize with LIN-1.