Iwanir, Shachar et al. (2015) International Worm Meeting "Serotonin promotes exploitation in complex environments by accelerating decision-making.."

Brown, Adam, Biron, David, Iwanir, Shachar, Najjar, Dana, Nagy, Stanislav

[International Worm Meeting, 2015]

When resources are not uniformly available, fast responses can provide a competitive advantage. The neurotransmitter serotonin (5-HT) was shown affect C. elegans locomotion on food in steady-state and following a period of food deprivation. We identified a novel role of 5-HT signaling in C. elegans: mediating a rapid response required for efficient exploitation in complex environments. Deficiency in 5-HT synthes­is, as well as genetic ablation of serotonergic neurons, resulted in gradual responses and defective exploitation. Both the ADF and NSM serotonergic neuronal types were implicated in these responses, albeit in different ways. Collectively, physiological imaging, genetic silencing, functional rescues, and optogenetic activation revealed that NSM responses initiated upon encounter and were key to rapid decision-making. In contrast, the onset of ADF responses preceded the physical encounter with the food. The relevance of responding rapidly was demonstrated in patchy environments, where the absence of 5-HT signaling significantly reduced exploitation. Collectively, our results suggest a novel role for 5-HT in decision-making, demonstrate its fitness consequences, and show that NSM and ADF act in concert to modulate locomotion in complex environments. .

Iwanir, Shachar et al. (2013) International Worm Meeting "A calcium-rich breakfast: physiological activity in C. elegans serotonergic neurons during the enhanced slowing response and upon emergence from lethargus."

Palmer, Meagan, Fitzgerald, Ivy, Brown, Adam, Iwanir, Shachar, Najjar, Dana, Biron, David

[International Worm Meeting, 2013]

Serotonin has been implicated in the assessment of resource availability and in the modulation of sleep in vertebrates. Extracellular serotonin levels in the hypothalamus are increased by the presence of food. Additionally, the firing of serotonergic cells in the brainstem raphe nuclei is tonic during wakefulness and significantly reduced during sleep states. In the nematode Caenorhabditis elegans, serotonin signaling has been shown to mediate the enhancing effect of starvation on the slowing response to encountering a food source. However, the understanding of the cellular mechanisms and physiological dynamics underlying this response is incomplete. We combined behavioral studies with physiological imaging of calcium dynamics in the serotonergic NSM and ADF neurons of freely-behaving animals in order to compare the responses to reintroduction of food in two situations: following a period of food deprivation and at the emergence from lethargus, a sleep-like state that involves a cessation of feeding. We identified similarities in the patterns of locomotion and physiological activity of NSM between these two circumstances. The enhanced slowing response was characterized by two phases: (i) preceding a spatial encounter with food, physiological activity in ADF neurons increased (likely via a chemosensory mechanism), concomitant with a gradual decrease in the rate of locomotion, and (ii) upon encountering food, NSM exhibited calcium transients lasting 1-2 minutes, accompanied by a sharp decrease in the rate of locomotion. Emergence from lethargus was associated with a period of extensive feeding and reduced locomotion, accompanied by a transient increased activity in NSM (but not ADF). Our results may point to a common origin of the modulation of serotonin signaling by arousal and feeding states, and suggest roles for both chemosensation and metabolic cues in the regulation of the enhanced slowing response.

Coux O (2003) Biochem Soc Trans "An interaction map of proteasome subunits."

Coux O

[Biochem Soc Trans, 2003]

Despite the central role of the 26 S proteasome in eukaryotic cells, many facets of its structural organization and functioning are still poorly understood. To learn more about the interactions between its different subunits, as well as its possible functional partners in cells, we performed, with Marc Vidal's laboratory (Dana-Farber Cancer Institute, Boston, MA, U.S.A.), a systematic two-hybrid analysis using Caenorhaditis elegans 26 S proteasome subunits as baits (Davy, Bello, Thierry-Mieg, Vaglio, Hitti, Doucette-Stamm, Thierry-Mieg, Reboul, Boulton, Walhout et al. (2001) EMBO Rep. 2, 821-828). A pair-wise matrix of all subunit combinations allowed us to detect numerous possible intra-complex interactions, among which some had already been reported by others and eight were novel. Interestingly, four new interactions were detected between two ATPases of the 19 S regulatory complex and three alpha-subunits of the 20 S proteolytic core. Possibly, these interactions participate in the association of these two complexes to form the 26 S proteasome. Proteasome subunit sequences were also used to screen a cDNA library to identify new interactors of the complex. Among the interactors found, most (58) have no clear connection to the proteasome, and could be either substrates or potential cofactors of this complex. Few interactors (7) could be directly or indirectly linked to proteolysis. The others (12) interacted with more than one proteasome subunit, forming 'interaction clusters' of

Soderlund CA et al. (1990) Worm Breeder's Gazette "gm Sequence Analysis System Update"

Soderlund CA, Fields CA, Shanmugam P

[Worm Breeder's Gazette, 1990]

A number of improvements have been made in the gm automated DNA sequence analysis system: (1) The ratio of AT-containing to CG-containing dinucleotides has been added as a test for introns. This works better than AT frequency alone in C. elegans.(2) A branch site consensus sequence or an enhanced dinucleotide ratio can be required as an additional test on introns. (3) Predicted amino-acid sequence files are generated in a format appropriate for input to the Dana-Farber motif-identification program plsearch. (4) A graphic interface based on X-windows, version 11 is available as an option. (5) The complete analysis algorithm is significantly faster than the previous version. (6) A greedy model evaluation algorithm is available as an option. This algorithm generates the longest, non-overlapping models that cover a sequence and is much faster than the complete analysis algorithm. The program has been tested on Sun3, Sun4 and VAX machines running Unix (Ultrix on the VAX). Results for a series of tests run on a Sun 4/60 are shown in the table. [See Figure 1] gm can be run remotely on our machine, using the Internet. To do this, telnet to haywire.nmsu.edu, and logon as gm_guest with password gmuser. Read the README file for information on running gm. We are also distributing gm as C source code to nonprofit laboratories, either via anonymous ftp to haywire.nmsu.edu, or on tape. If you would like to receive gm on tape, send a 1/4' cartridge or 1/2' reel tape to: Chris Fields, Box 30001/3CRL, New Mexico State University, Las Cruces, New Mexico 88003-0001, USA; Telephone (505) 646-2848.

Reboul J et al. (2001) Nat Genet "Open-reading-frame sequence tags (OSTs) support the existence of at least 17,300 genes in C. elegans."

Doucette-Stamm L, Lamesch PE, Reboul J, Temple GF, Hartley JL, Brasch MA, Hill DE, Vaglio P, Thierry-Mieg N, Shin-i T, Lee H, Moore T, Vandenhaute J, Kohara Y, Vidal M, Jackson C, Thierry-Mieg J, Tzellas N, Thierry-Mieg D, Hitti J

[Nat Genet, 2001]

The genome sequences of Caenorhabditis elegans, Drosophila melanogaster and Arabidopsis thaliana have been predicted to contain 19,000, 13,600 and 25,500 genes, respectively. Before this information can be fully used for evolutionary and functional studies, several issues need to be addressed. First, the gene number estimates obtained in silico and not yet supported by any experimental data need to be verified. For example, it seems biologically paradoxical that C. elegans would have 50% more genes than Drosophilia. Second, intron/exon predictions need to be tested experimentally. Third, complete sets of open reading frames (ORFs), or "ORFeomes," need to be cloned into various expression vectors. To address these issues simultaneously, we have designed and applied to C. elegans the following strategy. Predicted ORFs are amplified by PCR from a highly representative cDNA library using ORF-specific primers, cloned by Gateway recombination cloning and then sequenced to generate ORF sequence tags (OSTs) as a way to verify identity and splicing. In a sample (n=1,222) of the nearly 10,000 genes predicted ab initio (that is, for which no expressed sequence tag (EST) is available so far), at least 70% were verified by OSTs. We also observed that 27% of these experimentally confirmed genes have a structure different from that predicted by GeneFinder. We now have experimental evidence that supports the existence of at least 17,300 genes in C. elegans. Hence we suggest that gene counts based primarily on ESTs may underestimate the number of genes in human and in other organisms.AD - Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.FAU - Reboul, JAU - Reboul JFAU - Vaglio, PAU - Vaglio PFAU - Tzellas, NAU - Tzellas NFAU - Thierry-Mieg, NAU - Thierry-Mieg NFAU - Moore, TAU - Moore TFAU - Jackson, CAU - Jackson CFAU - Shin-i, TAU - Shin-i TFAU - Kohara, YAU - Kohara YFAU - Thierry-Mieg, DAU - Thierry-Mieg DFAU - Thierry-Mieg, JAU - Thierry-Mieg JFAU - Lee, HAU - Lee HFAU - Hitti, JAU - Hitti JFAU - Doucette-Stamm, LAU - Doucette-Stamm LFAU - Hartley, J LAU - Hartley JLFAU - Temple, G FAU - Temple GFFAU - Brasch, M AAU - Brasch MAFAU - Vandenhaute, JAU - Vandenhaute JFAU - Lamesch, P EAU - Lamesch PEFAU - Hill, D EAU - Hill DEFAU - Vidal, MAU - Vidal MLA - engID - R21 CA81658 A 01/CA/NCIID - RO1 HG01715-01/HG/NHGRIPT - Journal ArticleCY - United StatesTA - Nat GenetJID - 9216904SB - IM