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Identification Of Lipid Droplet Structure-Like/Resident Proteins In Caenorhabditis Elegans., Huimin Na, Peng Zhang, Yong Chen, Xiaotong Zhu, Yi Liu, Yangli Liu, Kang Xie, Ningyi Xu, Fuquan Yang, Yong Yu, Simon Cichello, Ho Yi Mak, Meng C Wang, Hong Zhang, Pingsheng Liu Sep 2019

Identification Of Lipid Droplet Structure-Like/Resident Proteins In Caenorhabditis Elegans., Huimin Na, Peng Zhang, Yong Chen, Xiaotong Zhu, Yi Liu, Yangli Liu, Kang Xie, Ningyi Xu, Fuquan Yang, Yong Yu, Simon Cichello, Ho Yi Mak, Meng C Wang, Hong Zhang, Pingsheng Liu

Yong Chen

The lipid droplet (LD) is a cellular organelle that stores neutral lipids in cells and has been linked with metabolic disorders. Caenorhabditis elegans has many characteristics which make it an excellent animal model for studying LDs. However, unlike in mammalian cells, no LD structure-like/resident proteins have been identified in C. elegans, which has limited the utility of this model for the study of lipid storage and metabolism. Herein based on three lines of evidence, we identified that MDT-28 and DHS-3 previously identified in C. elegans LD proteome were two LD structure-like/resident proteins. First, MDT-28 and DHS-3 were found to be …


Cerium Oxide Nanoparticle Aggregates Affect Stress Response And Function In Caenorhabditis Elegans, Steven Rogers, Kevin M. Rice, Nandini Manne, Tolou Shokuhfar, Kun He, Vellaisamy Selvaraj, Eric Blough Feb 2018

Cerium Oxide Nanoparticle Aggregates Affect Stress Response And Function In Caenorhabditis Elegans, Steven Rogers, Kevin M. Rice, Nandini Manne, Tolou Shokuhfar, Kun He, Vellaisamy Selvaraj, Eric Blough

Eric Blough

Objective: The continual increase in production and disposal of nanomaterials raises concerns regarding the safety of nanoparticles on the environmental and human health. Recent studies suggest that cerium oxide (CeO2) nanoparticles may possess both harmful and beneficial effects on biological processes. The primary objective of this study is to evaluate how exposure to different concentrations (0.17–17.21 µg/mL) of aggregated CeO2 nanoparticles affects indices of whole animal stress and survivability in Caenorhabditis elegans.

Methods: Caenorhabditis elegans were exposed to different concentrations of CeO2 nanoparticles and evaluated.

Results: Our findings demonstrate that chronic exposure of CeO2 nanoparticle aggregates is …


Cerium Oxide Nanoparticle Aggregates Affect Stress Response And Function In Caenorhabditis Elegans, Steven Rogers, Kevin M. Rice, Nandini Manne, Tolou Shokuhfar, Kun He, Vellaisamy Selvaraj, Eric Blough Feb 2018

Cerium Oxide Nanoparticle Aggregates Affect Stress Response And Function In Caenorhabditis Elegans, Steven Rogers, Kevin M. Rice, Nandini Manne, Tolou Shokuhfar, Kun He, Vellaisamy Selvaraj, Eric Blough

Nandini Manne

Objective: The continual increase in production and disposal of nanomaterials raises concerns regarding the safety of nanoparticles on the environmental and human health. Recent studies suggest that cerium oxide (CeO2) nanoparticles may possess both harmful and beneficial effects on biological processes. The primary objective of this study is to evaluate how exposure to different concentrations (0.17–17.21 µg/mL) of aggregated CeO2 nanoparticles affects indices of whole animal stress and survivability in Caenorhabditis elegans.

Methods: Caenorhabditis elegans were exposed to different concentrations of CeO2 nanoparticles and evaluated.

Results: Our findings demonstrate that chronic exposure of CeO2 nanoparticle aggregates is …


Cerium Oxide Nanoparticle Aggregates Affect Stress Response And Function In Caenorhabditis Elegans, Steven Rogers, Kevin M. Rice, Nandini Manne, Tolou Shokuhfar, Kun He, Vellaisamy Selvaraj, Eric Blough Feb 2018

Cerium Oxide Nanoparticle Aggregates Affect Stress Response And Function In Caenorhabditis Elegans, Steven Rogers, Kevin M. Rice, Nandini Manne, Tolou Shokuhfar, Kun He, Vellaisamy Selvaraj, Eric Blough

Kevin M Rice

Objective: The continual increase in production and disposal of nanomaterials raises concerns regarding the safety of nanoparticles on the environmental and human health. Recent studies suggest that cerium oxide (CeO2) nanoparticles may possess both harmful and beneficial effects on biological processes. The primary objective of this study is to evaluate how exposure to different concentrations (0.17–17.21 µg/mL) of aggregated CeO2 nanoparticles affects indices of whole animal stress and survivability in Caenorhabditis elegans.

Methods: Caenorhabditis elegans were exposed to different concentrations of CeO2 nanoparticles and evaluated.

Results: Our findings demonstrate that chronic exposure of CeO2 nanoparticle aggregates is …


Caenorhabditis Elegans Alg-1 Antimorphic Mutations Uncover Functions For Argonaute In Microrna Guide Strand Selection And Passenger Strand Disposal, Anna Y. Zinovyeva, Isana Veksler-Lublinsky, Ajay A. Vashisht, James A. Wohlschlegel, Victor R. Ambros Oct 2015

Caenorhabditis Elegans Alg-1 Antimorphic Mutations Uncover Functions For Argonaute In Microrna Guide Strand Selection And Passenger Strand Disposal, Anna Y. Zinovyeva, Isana Veksler-Lublinsky, Ajay A. Vashisht, James A. Wohlschlegel, Victor R. Ambros

Victor R. Ambros

MicroRNAs are regulators of gene expression whose functions are critical for normal development and physiology. We have previously characterized mutations in a Caenorhabditis elegans microRNA-specific Argonaute ALG-1 (Argonaute-like gene) that are antimorphic [alg-1(anti)]. alg-1(anti) mutants have dramatically stronger microRNA-related phenotypes than animals with a complete loss of ALG-1. ALG-1(anti) miRISC (microRNA induced silencing complex) fails to undergo a functional transition from microRNA processing to target repression. To better understand this transition, we characterized the small RNA and protein populations associated with ALG-1(anti) complexes in vivo. We extensively characterized proteins associated with wild-type and mutant ALG-1 and found that the mutant …


Robust Distal Tip Cell Pathfinding In The Face Of Temperature Stress Is Ensured By Two Conserved Micrornas In Caenorhabditis Elegans, Samantha L. Burke, Molly Hammell, Victor R. Ambros Oct 2015

Robust Distal Tip Cell Pathfinding In The Face Of Temperature Stress Is Ensured By Two Conserved Micrornas In Caenorhabditis Elegans, Samantha L. Burke, Molly Hammell, Victor R. Ambros

Victor R. Ambros

Biological robustness, the ability of an organism to maintain a steady-state output as genetic or environmental inputs change, is critical for proper development. MicroRNAs have been implicated in biological robustness mechanisms through their post-transcriptional regulation of genes and gene networks. Previous research has illustrated examples of microRNAs promoting robustness as part of feedback loops and genetic switches and by buffering noisy gene expression resulting from environmental and/or internal changes. Here we show that the evolutionarily conserved microRNAs mir-34 and mir-83 (homolog of mammalian mir-29) contribute to the robust migration pattern of the distal tip cells in Caenorhabditis elegans by specifically …


Genome-Scale Spatiotemporal Analysis Of Caenorhabditis Elegans Microrna Promoter Activity, Natalia Julia Martinez, Maria C. Ow, John S. Reece-Hoyes, M. Inmaculada Barrasa, Victor R. Ambros, Albertha J. M. Walhout Oct 2015

Genome-Scale Spatiotemporal Analysis Of Caenorhabditis Elegans Microrna Promoter Activity, Natalia Julia Martinez, Maria C. Ow, John S. Reece-Hoyes, M. Inmaculada Barrasa, Victor R. Ambros, Albertha J. M. Walhout

Victor R. Ambros

The Caenorhabditis elegans genome encodes more than 100 microRNAs (miRNAs). Genetic analyses of miRNA deletion mutants have only provided limited insights into miRNA function. To gain insight into the function of miRNAs, it is important to determine their spatiotemporal expression pattern. Here, we use miRNA promoters driving the expression of GFP as a proxy for miRNA expression. We describe a set of 73 transgenic C. elegans strains, each expressing GFP under the control of a miRNA promoter. Together, these promoters control the expression of 89 miRNAs (66% of all predicted miRNAs). We find that miRNA promoters drive GFP expression in …


Inhibiting Mirna In Caenorhabditis Elegans Using A Potent And Selective Antisense Reagent, Genhua Zheng, Victor R. Ambros, Wen-Hong Li Oct 2015

Inhibiting Mirna In Caenorhabditis Elegans Using A Potent And Selective Antisense Reagent, Genhua Zheng, Victor R. Ambros, Wen-Hong Li

Victor R. Ambros

BACKGROUND: Antisense reagents can serve as efficient and versatile tools for studying gene function by inhibiting nucleic acids in vivo. Antisense reagents have particular utility for the experimental manipulation of the activity of microRNAs (miRNAs), which are involved in the regulation of diverse developmental and physiological pathways in animals. Even in traditional genetic systems, such as the nematode Caenorhabditis elegans, antisense reagents can provide experimental strategies complementary to mutational approaches. Presently no antisense reagents are available for inhibiting miRNAs in the nematode C. elegans. RESULTS: We have developed a new class of fluorescently labelled antisense reagents to inhibit miRNAs in …


Mutations In Conserved Residues Of The C. Elegans Microrna Argonaute Alg-1 Identify Separable Functions In Alg-1 Mirisc Loading And Target Repression, Anna Y. Zinovyeva, Samir Bouasker, Martin J. Simard, Christopher M. Hammell, Victor R. Ambros Oct 2015

Mutations In Conserved Residues Of The C. Elegans Microrna Argonaute Alg-1 Identify Separable Functions In Alg-1 Mirisc Loading And Target Repression, Anna Y. Zinovyeva, Samir Bouasker, Martin J. Simard, Christopher M. Hammell, Victor R. Ambros

Victor R. Ambros

microRNAs function in diverse developmental and physiological processes by regulating target gene expression at the post-transcriptional level. ALG-1 is one of two Caenorhabditis elegans Argonautes (ALG-1 and ALG-2) that together are essential for microRNA biogenesis and function. Here, we report the identification of novel antimorphic (anti) alleles of ALG-1 as suppressors of lin-28(lf) precocious developmental phenotypes. The alg-1(anti) mutations broadly impair the function of many microRNAs and cause dosage-dependent phenotypes that are more severe than the complete loss of ALG-1. ALG-1(anti) mutant proteins are competent for promoting Dicer cleavage of microRNA precursors and for associating with and stabilizing microRNAs. However, …


Caenorhabditis Elegans Micrornas Of The Let-7 Family Act In Innate Immune Response Circuits And Confer Robust Developmental Timing Against Pathogen Stress, Zhiji Ren, Victor R. Ambros Oct 2015

Caenorhabditis Elegans Micrornas Of The Let-7 Family Act In Innate Immune Response Circuits And Confer Robust Developmental Timing Against Pathogen Stress, Zhiji Ren, Victor R. Ambros

Victor R. Ambros

Animals maintain their developmental robustness against natural stresses through numerous regulatory mechanisms, including the posttranscriptional regulation of gene expression by microRNAs (miRNAs). Caenorhabditis elegans miRNAs of the let-7 family (let-7-Fam) function semiredundantly to confer robust stage specificity of cell fates in the hypodermal seam cell lineages. Here, we show reciprocal regulatory interactions between let-7-Fam miRNAs and the innate immune response pathway in C. elegans. Upon infection of C. elegans larvae with the opportunistic human pathogen Pseudomonas aeruginosa, the developmental timing defects of certain let-7-Fam miRNA mutants are enhanced. This enhancement is mediated by the p38 MAPK innate immune pathway acting …


Effect Of Life History On Microrna Expression During C. Elegans Development, Xantha Karp, Molly Hammell, Maria C. Ow, Victor R. Ambros Oct 2015

Effect Of Life History On Microrna Expression During C. Elegans Development, Xantha Karp, Molly Hammell, Maria C. Ow, Victor R. Ambros

Victor R. Ambros

Animals have evolved mechanisms to ensure the robustness of developmental outcomes to changing environments. MicroRNA expression may contribute to developmental robustness because microRNAs are key post-transcriptional regulators of developmental gene expression and can affect the expression of multiple target genes. Caenorhabditis elegans provides an excellent model to study developmental responses to environmental conditions. In favorable environments, C. elegans larvae develop rapidly and continuously through four larval stages. In contrast, in unfavorable conditions, larval development may be interrupted at either of two diapause stages: The L1 diapause occurs when embryos hatch in the absence of food, and the dauer diapause occurs …


The Flywch Transcription Factors Flh-1, Flh-2, And Flh-3 Repress Embryonic Expression Of Microrna Genes In C. Elegans, Maria C. Ow, Natalia Julia Martinez, Philip H. Olsen, Howard S. Silverman, M. Inmaculada Barrasa, Barbara Conradt, Albertha J. M. Walhout, Victor R. Ambros Oct 2015

The Flywch Transcription Factors Flh-1, Flh-2, And Flh-3 Repress Embryonic Expression Of Microrna Genes In C. Elegans, Maria C. Ow, Natalia Julia Martinez, Philip H. Olsen, Howard S. Silverman, M. Inmaculada Barrasa, Barbara Conradt, Albertha J. M. Walhout, Victor R. Ambros

Victor R. Ambros

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally via antisense base-pairing. Although miRNAs are involved in a variety of important biological functions, little is known about their transcriptional regulation. Using yeast one-hybrid assays, we identified transcription factors with a FLYWCH Zn-finger DNA-binding domain that bind to the promoters of several Caenorhabditis elegans miRNA genes. The products of the flh-1 and flh-2 genes function redundantly to repress embryonic expression of lin-4, mir-48, and mir-241, miRNA genes that are normally expressed only post-embryonically. Although single mutations in either flh-1 or flh-2 genes result in a viable phenotype, double mutation …


A C. Elegans Genome-Scale Microrna Network Contains Composite Feedback Motifs With High Flux Capacity, Natalia Julia Martinez, Maria C. Ow, M. Inmaculada Barrasa, Molly Hammell, Reynaldo Sequerra, Lynn Doucette-Stamm, Frederick P. Roth, Victor R. Ambros, Albertha J. M. Walhout Oct 2015

A C. Elegans Genome-Scale Microrna Network Contains Composite Feedback Motifs With High Flux Capacity, Natalia Julia Martinez, Maria C. Ow, M. Inmaculada Barrasa, Molly Hammell, Reynaldo Sequerra, Lynn Doucette-Stamm, Frederick P. Roth, Victor R. Ambros, Albertha J. M. Walhout

Victor R. Ambros

MicroRNAs (miRNAs) and transcription factors (TFs) are primary metazoan gene regulators. Whereas much attention has focused on finding the targets of both miRNAs and TFs, the transcriptional networks that regulate miRNA expression remain largely unexplored. Here, we present the first genome-scale Caenorhabditis elegans miRNA regulatory network that contains experimentally mapped transcriptional TF --> miRNA interactions, as well as computationally predicted post-transcriptional miRNA --> TF interactions. We find that this integrated miRNA network contains 23 miRNA <--> TF composite feedback loops in which a TF that controls a miRNA is itself regulated by that same miRNA. By rigorous network randomizations, we show …


Most Caenorhabditis Elegans Micrornas Are Individually Not Essential For Development Or Viability, Eric A. Miska, Ezequiel Alvarez-Saavedra, Allison Abbott, Nelson C. Lau, Andrew B. Hellman, Shannon M. Mcgonagle, David P. Bartel, Victor R. Ambros, H. Robert Horvitz Oct 2015

Most Caenorhabditis Elegans Micrornas Are Individually Not Essential For Development Or Viability, Eric A. Miska, Ezequiel Alvarez-Saavedra, Allison Abbott, Nelson C. Lau, Andrew B. Hellman, Shannon M. Mcgonagle, David P. Bartel, Victor R. Ambros, H. Robert Horvitz

Victor R. Ambros

MicroRNAs (miRNAs), a large class of short noncoding RNAs found in many plants and animals, often act to post-transcriptionally inhibit gene expression. We report the generation of deletion mutations in 87 miRNA genes in Caenorhabditis elegans, expanding the number of mutated miRNA genes to 95, or 83% of known C. elegans miRNAs. We find that the majority of miRNAs are not essential for the viability or development of C. elegans, and mutations in most miRNA genes do not result in grossly abnormal phenotypes. These observations are consistent with the hypothesis that there is significant functional redundancy among miRNAs or among …


A Feedback Circuit Involving Let-7-Family Mirnas And Daf-12 Integrates Environmental Signals And Developmental Timing In Caenorhabditis Elegans, Christopher M. Hammell, Xantha Karp, Victor R. Ambros Nov 2009

A Feedback Circuit Involving Let-7-Family Mirnas And Daf-12 Integrates Environmental Signals And Developmental Timing In Caenorhabditis Elegans, Christopher M. Hammell, Xantha Karp, Victor R. Ambros

Victor R. Ambros

Animal development is remarkably robust; cell fates are specified with spatial and temporal precision despite physiological and environmental contingencies. Favorable conditions cause Caenorhabditis elegans to develop rapidly through four larval stages (L1-L4) to the reproductive adult. In unfavorable conditions, L2 larvae can enter the developmentally quiescent, stress-resistant dauer larva stage, enabling them to survive for prolonged periods before completing development. A specific progression of cell division and differentiation events occurs with fidelity during the larval stages, regardless of whether an animal undergoes continuous or dauer-interrupted development. The temporal patterning of developmental events is controlled by the heterochronic genes, whose products …


Interacting Endogenous And Exogenous Rnai Pathways In Caenorhabditis Elegans., Rosalind C. Lee, Christopher M. Hammell, Victor R. Ambros Mar 2006

Interacting Endogenous And Exogenous Rnai Pathways In Caenorhabditis Elegans., Rosalind C. Lee, Christopher M. Hammell, Victor R. Ambros

Victor R. Ambros

C. elegans contains numerous small RNAs of ~21-24 nt in length. The microRNAs (miRNAs) are small noncoding RNAs produced by DCR-1- and ALG-dependent processing of self-complementary hairpin transcripts. Endogenous small interfering RNAs (endo-siRNAs), associated with ongoing silencing of protein-coding genes in normal worms, are produced by mechanisms that involve DCR-1 but, unlike miRNAs, also involve RDE-2, RDE-3, RDE-4, RRF-1, and RRF-3. The tiny noncoding (tncRNAs) are similar to endo-siRNAs in their biogenesis except that they are derived from noncoding sequences. These endo-siRNA- and tncRNA-based endogenous RNAi pathways involve some components, including DCR-1 and RDE-4, that are shared with exogenous RNAi, …


The Caenorhabditis Elegans Heterochronic Regulator Lin-14 Is A Novel Transcription Factor That Controls The Developmental Timing Of Transcription From The Insulin/Insulin-Like Growth Factor Gene Ins-33 By Direct Dna Binding., Marta Hristova, Darcy Birse, Yang Hong, Victor R. Ambros Nov 2005

The Caenorhabditis Elegans Heterochronic Regulator Lin-14 Is A Novel Transcription Factor That Controls The Developmental Timing Of Transcription From The Insulin/Insulin-Like Growth Factor Gene Ins-33 By Direct Dna Binding., Marta Hristova, Darcy Birse, Yang Hong, Victor R. Ambros

Victor R. Ambros

A temporal gradient of the novel nuclear protein LIN-14 specifies the timing and sequence of stage-specific developmental events in Caenorhabditis elegans. The profound effects of lin-14 mutations on worm development suggest that LIN-14 directly or indirectly regulates stage-specific gene expression. We show that LIN-14 can associate with chromatin in vivo and has in vitro DNA binding activity. A bacterially expressed C-terminal domain of LIN-14 was used to select DNA sequences that contain a putative consensus binding site from a pool of randomized double-stranded oligonucleotides. To identify candidates for genes directly regulated by lin-14, we employed DNA microarray hybridization to compare …


Structure And Function Analysis Of Lin-14, A Temporal Regulator Of Postembryonic Developmental Events In Caenorhabditis Elegans, Yang Hong, Rosalind C. Lee, Victor R. Ambros Feb 2000

Structure And Function Analysis Of Lin-14, A Temporal Regulator Of Postembryonic Developmental Events In Caenorhabditis Elegans, Yang Hong, Rosalind C. Lee, Victor R. Ambros

Victor R. Ambros

During postembryonic development of Caenorhabditis elegans, the heterochronic gene lin-14 controls the timing of developmental events in diverse cell types. Three alternative lin-14 transcripts are predicted to encode isoforms of a novel nuclear protein that differ in their amino-terminal domains. In this paper, we report that the alternative amino-terminal domains of LIN-14 are dispensable and that a carboxy-terminal region within exons 9 to 13 is necessary and sufficient for in vivo LIN-14 function. A transgene capable of expressing only one of the three alternative lin-14 gene products rescues a lin-14 null mutation and is developmentally regulated by lin-4. This shows …


Heterochronic Genes Control The Stage-Specific Initiation And Expression Of The Dauer Larva Developmental Program In Caenorhabditis Elegans, Zhongchi Liu, Victor R. Ambros Nov 1989

Heterochronic Genes Control The Stage-Specific Initiation And Expression Of The Dauer Larva Developmental Program In Caenorhabditis Elegans, Zhongchi Liu, Victor R. Ambros

Victor R. Ambros

We report that a stage-specific developmental program, dauer larva formation, is temporally regulated by four heterochronic genes, lin-4, lin-14, lin-28, and lin-29. The effects of mutations in these four genes on dauer larva formation have revealed that they regulate two different processes of dauer larva formation: (1) a decision specifying the larval stage at which dauer larva development initiates, and (2) the specialized differentiation of hypodermal cells during dauer larva morphogenesis. Epistasis analysis has suggested a model in which lin-4 negatively regulates lin-14, and the resulting temporal decrease in lin-14 activity specifies the stage of dauer larva initiation. Our results …


The Lin-14 Locus Of Caenorhabditis Elegans Controls The Time Of Expression Of Specific Postembryonic Developmental Events, Victor R. Ambros, H. Robert Horvitz May 1987

The Lin-14 Locus Of Caenorhabditis Elegans Controls The Time Of Expression Of Specific Postembryonic Developmental Events, Victor R. Ambros, H. Robert Horvitz

Victor R. Ambros

The lin-14 locus of Caenorhabditis elegans plays an important role in specifying the normal timing and sequence of developmental events in the lateral hypodermal cell lineages. The results of gene dosage, complementation, and temperature-shift experiments indicate that the fates expressed by cells at successive stages of these cell lineages are specified by the level of lin-14 activity and that lin-14 acts at multiple times during development to control stage-specific choices of cell fate. Our observations suggest that during normal development a reduction in the level of lin-14 gene function causes the sequential expression of stage-specific cell fates.