Biochemistry Commons^™

Rna Recognition By The Caenorhabditis Elegans Oocyte Maturation Determinant Oma-1, Ebru Kaymak, Sean Ryder

Sean P. Ryder

Maternally supplied mRNAs encode proteins that pattern early embryos in many species. In the nematode Caenorhabditis elegans, a suite of RNA-binding proteins regulates expression of maternal mRNAs during oogenesis, the oocyte to embryo transition, and early embryogenesis. To understand how these RNA-binding proteins contribute to development, it is necessary to determine how they select specific mRNA targets for regulation. OMA-1 and OMA-2 are redundant proteins required for oocyte maturation--an essential part of meiosis that prepares oocytes for fertilization. Both proteins have CCCH type tandem zinc finger RNA-binding domains. Here, we define the RNA binding specificity of OMA-1 and demonstrate that …

Control Of Stem Cell Self-Renewal And Differentiation By The Heterochronic Genes And The Cellular Asymmetry Machinery In Caenorhabditis Elegans, Omid F. Harandi, Victor Ambros

Victor R. Ambros

Transitions between asymmetric (self-renewing) and symmetric (proliferative) cell divisions are robustly regulated in the context of normal development and tissue homeostasis. To genetically assess the regulation of these transitions, we used the postembryonic epithelial stem (seam) cell lineages of Caenorhabditis elegans. In these lineages, the timing of these transitions is regulated by the evolutionarily conserved heterochronic pathway, whereas cell division asymmetry is conferred by a pathway consisting of Wnt (Wingless) pathway components, including posterior pharynx defect (POP-1)/TCF, APC related/adenomatosis polyposis coli (APR-1)/APC, and LIT-1/NLK (loss of intestine/Nemo-like kinase). Here we explore the genetic regulatory mechanisms underlying stage-specific transitions between self-renewing …

Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang

Victor R. Ambros

Like mammalian neurons, Caenorhabditis elegans neurons lose axon regeneration ability as they age, but it is not known why. Here, we report that let-7 contributes to a developmental decline in anterior ventral microtubule (AVM) axon regeneration. In older AVM axons, let-7 inhibits regeneration by down-regulating LIN-41, an important AVM axon regeneration-promoting factor. Whereas let-7 inhibits lin-41 expression in older neurons through the lin-41 3' untranslated region, lin-41 inhibits let-7 expression in younger neurons through Argonaute ALG-1. This reciprocal inhibition ensures that axon regeneration is inhibited only in older neurons. These findings show that a let-7-lin-41 regulatory circuit, which was previously …

The Evolution Of Our Thinking About Micrornas, Victor Ambros

Victor R. Ambros

Our appreciation of the significance of microRNAs to biology at large continues to be an evolving process.

The Developmental Timing Regulator Hbl-1 Modulates The Dauer Formation Decision In Caenorhabditis Elegans, Xantha Karp, Victor Ambros

Victor R. Ambros

Animals developing in the wild encounter a range of environmental conditions, and so developmental mechanisms have evolved that can accommodate different environmental contingencies. Harsh environmental conditions cause Caenorhabditis elegans larvae to arrest as stress-resistant "dauer" larvae after the second larval stage (L2), thereby indefinitely postponing L3 cell fates. HBL-1 is a key transcriptional regulator of L2 vs. L3 cell fate. Through the analysis of genetic interactions between mutations of hbl-1 and of genes encoding regulators of dauer larva formation, we find that hbl-1 can also modulate the dauer formation decision in a complex manner. We propose that dynamic interactions between …

Mir-14 Regulates Autophagy During Developmental Cell Death By Targeting Ip3-Kinase 2, Charles Nelson, Victor Ambros, Eric Baehrecke

Victor R. Ambros

Macroautophagy (autophagy) is a lysosome-dependent degradation process that has been implicated in age-associated diseases. Autophagy is involved in both cell survival and cell death, but little is known about the mechanisms that distinguish its use during these distinct cell fates. Here, we identify the microRNA miR-14 as being both necessary and sufficient for autophagy during developmentally regulated cell death in Drosophila. Loss of miR-14 prevented induction of autophagy during salivary gland cell death, but had no effect on starvation-induced autophagy in the fat body. Moreover, misexpression of miR-14 was sufficient to prematurely induce autophagy in salivary glands, but not in …

Micrornas And Developmental Timing, Victor Ambros

Victor R. Ambros

MicroRNAs regulate temporal transitions in gene expression associated with cell fate progression and differentiation throughout animal development. Genetic analysis of developmental timing in the nematode Caenorhabditis elegans identified two evolutionarily conserved microRNAs, lin-4/mir-125 and let-7, that regulate cell fate progression and differentiation in C. elegans cell lineages. MicroRNAs perform analogous developmental timing functions in other animals, including mammals. By regulating cell fate choices and transitions between pluripotency and differentiation, microRNAs help to orchestrate developmental events throughout the developing animal, and to play tissue homeostasis roles important for disease, including cancer.

Dauer Larva Quiescence Alters The Circuitry Of Microrna Pathways Regulating Cell Fate Progression In C. Elegans, Xantha Karp, Victor Ambros

Victor R. Ambros

In C. elegans larvae, the execution of stage-specific developmental events is controlled by heterochronic genes, which include those encoding a set of transcription factors and the microRNAs that regulate the timing of their expression. Under adverse environmental conditions, developing larvae enter a stress-resistant, quiescent stage called 'dauer'. Dauer larvae are characterized by the arrest of all progenitor cell lineages at a stage equivalent to the end of the second larval stage (L2). If dauer larvae encounter conditions favorable for resumption of reproductive growth, they recover and complete development normally, indicating that post-dauer larvae possess mechanisms to accommodate an indefinite period …

Micrornas: Genetically Sensitized Worms Reveal New Secrets, Victor Ambros

Victor R. Ambros

Why do many microRNA gene mutants display no evident phenotype? Multiply mutant worms that are selectively impaired in genetic regulatory network activities have been used to uncover previously unknown functions for numerous Caenorhabditis elegans microRNAs.

Prb/Cki Pathways At The Interface Of Cell Cycle And Development, Victor Ambros

Victor R. Ambros

Comment on: The cyclin-dependent kinase inhibitors, cki-1 and cki-2, act in overlapping but distinct pathways to control cell-cycle quiescence during C. elegans development. Buck SH, et al. Cell Cycle 2009; 8:2613-20.

Stomatin-Like Protein 2 Deficiency In T Cells Is Associated With Altered Mitochondrial Respiration And Defective Cd4+ T Cell Responses., Darah A Christie, Panagiotis Mitsopoulos, Julianna Blagih, Stanley D Dunn, Julie St-Pierre, Russell G Jones, Grant M Hatch, Joaquín Madrenas

Stanley D Dunn

Stomatin-like protein 2 (SLP-2) is a mostly mitochondrial protein that regulates mitochondrial biogenesis and function and modulates T cell activation. To determine the mechanism of action of SLP-2, we generated T cell-specific SLP-2-deficient mice. These mice had normal numbers of thymocytes and T cells in the periphery. However, conventional SLP-2-deficient T cells had a posttranscriptional defect in IL-2 production in response to TCR ligation, and this translated into reduced CD4(+) T cell responses. SLP-2 deficiency was associated with impaired cardiolipin compartmentalization in mitochondrial membranes, decreased levels of the NADH dehydrogenase (ubiquinone) iron-sulfur protein 3, NADH dehydrogenase (ubiquinone) 1β subcomplex subunit …

Guanosine Diphosphatase Is Required For Protein And Sphingolipid Glycosylation In The Golgi Lumen Of Saccharomyces Cerevisiae, Claudia Abeijon, Ken Yanagisawa, Elisabet Mandon, Alex Hausler, Kelley Moremen, Carlos Hirschberg, Phillips Robbins

Elisabet Mandon

Current models for nucleotide sugar use in the Golgi apparatus predict a critical role for the lumenal nucleoside diphosphatase. After transfer of sugars to endogenous macromolecular acceptors, the enzyme converts nucleoside diphosphates to nucleoside monophosphates which in turn exit the Golgi lumen in a coupled antiporter reaction, allowing entry of additional nucleotide sugar from the cytosol. To test this model, we cloned the gene for the S. cerevisiae guanosine diphosphatase and constructed a null mutation. This mutation should reduce the concentrations of GDP-mannose and GMP and increase the concentration of GDP in the Golgi lumen. The alterations should in turn …

Viability Of Lactic Acid Bacteria And Sensory Evaluation In Cinnamomum Verum And Allium Sativum-Bio-Yogurts Made From Camel And Cow Milk, Ahmad Salihin Hj Baba, Shori A. B.

Ahmad Salihin Hj Baba

The present study investigate the effect of herbal water extract prepared from Allium sativum and Cinnamomum verum on the viability of lactic acid bacteria (Lactobacillus spp and Streptococcus thermophilus) in cow- and camel-milk yogurts during 21 day refrigerated storage. The organoleptic properties of fresh-yogurts were evaluated. Lactobacillus spp count for fresh cow milk-yogurts (0 day) in both present and absent of C. verum and A. sativum was ranged from 1.4×0 6 to 2.1×10 6 cfu/mL. These values were not significantly changed throughout the 21 days of refrigerated storage. Lactobacillusspp count in fresh plain camel milk- yogurt was 13.2×10 6 cfu/mL …

Micrornas Are Independent Predictors Of Outcome In Diffuse Large B-Cell Lymphoma Patients Treated With R-Chop, Goldi Kozloski

Goldi A Kozloski

Mechanistic And Signaling Analysis Of Muc4-Erbb2 Signaling Module: New Insights Into The Mechanism Of Ligand-Independent Erbb2 Activity, Goldi Kozloski

Goldi A Kozloski

Muc4/Muc4 Functions And Regulation In Cancer., Goldi Kozloski

Goldi A Kozloski

Conformational Changes In Receptor Tyrosine Kinase Signaling: An Erbb Garden Of Delights., Goldi Kozloski

Goldi A Kozloski

Growth And Reproductive Performance Of Small Ruminants Under Integrated Livestock Oil Palm Production System, Ahmad Salihin Hj Baba, Azillah A., Mukherjee T. K., Abdullah R. B.

Ahmad Salihin Hj Baba

The effects of supplementation with mixed fodder or concentrate were investigated on the performance of a) growth of male lambs;md kids grazing extensively under oil palm trees and b) reproduction of ewes and goats stall-fed with native herbage. Supplemented kids and lambs had higher average daily weight gain than controls but the effect was only significant for those which received concentrate (p < 0.05). Final body weight was only significantly different from controls for lambs supplemented with concentrate (p < 0.05). The ages at puberty, first mating, first conception and first kidding of supplemented goats were about 110 days earlier than those for controls (p < 0.05 or better). Supplemented goats had first mating and conceived at lower body weights (p < 0.01) than those in control groups. Different feeding regimes had no effects (p > 0.05) on the reproductive performance of ewes apart fi om highest body weight of first lambing in animals supplemented with concentrate (p < 0.05). Native herbage available under oil palm trees of 5 years old was sufficient for growth …