Strauss E (2001) Science "Longevity. Growing old together."

Strauss E

[Science, 2001]

Simple evolutionary arguments don't demand that organisms share mechanisms of aging. But new work is strengthening the case that common processes control the life-spans of biology's favorite model systems.

Dhakal, Pravat et al. (2021) International Worm Meeting "Galphaq acts via DAG signaling to modulate serotonin motor circuit activity in C. elegans"

Collins, Kevin M., Dhakal, Pravat, Chaudhry, Sana, Signorelli, Rossana, Case, Caroline

[International Worm Meeting, 2021]

Galphaq signals through the Phospholipase-Cbeta (PLCbeta) and Trio, a Rho GTPase exchange factor (RhoGEF), but how these two effector pathways promote synaptic transmission remains poorly understood. Here we use the egg-laying behavior circuit of C. elegans to show that PLCbeta/EGL-8 and Trio/UNC-73 mediate serotonin signaling through related biochemical pathways but by functioning in distinct cells. Using transgenic rescue experiments we find that PLCbeta functions in neurons while Trio functions in both neurons and the postsynaptic vulval muscles. Additionally, cell specific activation of Rho GTPase/Rho-1 in the serotonergic HSN neurons promotes synaptic transmission, associated with increase in HSN activity and egg-laying behavior. While Galphaq, PLCbeta, and Trio mutants all fail to lay eggs in response to serotonin, optogenetic stimulation of the serotonin-releasing HSNs restores egg laying only in PLCbeta mutants. We observed vulval muscle Ca2+ activity in PLCbeta mutants while such activity was eliminated in strong Galphaq and Trio mutants. Remarkably, egg-laying circuit activity and behavior defects of Galphaq, PLCbeta, and Trio mutants were rescued by Phorbol esters thought to mimic Diacylglycerol (DAG), a product of PIP2 hydrolysis by Phospholipases like PLCbeta/EGL-8. DAG has been proposed to activate effectors including UNC-13, but we find that phorbol esters, but not serotonin, stimulate egg-laying behavior in unc-13 mutants. Together, these results show that serotonin and Galphaq promote egg laying via two parallel mechanisms. Serotonin signaling through Galphaq and PLCbeta modulates UNC-13 activity to promote neurotransmitter release. Serotonin Galphaq signaling through Trio RhoGEF- Rho GTPase and an unidentified, PMA-responsive effector promotes postsynaptic muscle excitability. Thus, one neuromodulator can signal in distinct cells through different effector pathways to activate a motor behavior circuit.

Davies T et al. (2023) Curr Biol "Cell-cycle control: Timing is everything for the Plk1-Bub1 partnership."

Davies T, Hardwick KG

[Curr Biol, 2023]

Bub1 and Polo kinases are well-known multitasking regulators of mitosis. New work shows that they team up at kinetochores to determine the mitotic duration of embryonic divisions in nematodes. As is often the case, the key effector is Cdc20 activity.

Riddle DL et al. (1978) Genetics "Indirect suppression in Caenorhabditis elegans."

Brenner S, Riddle DL

[Genetics, 1978]

Two cases of indirect suppression have been characterized. One case involves suppressors compensating for defects in muscle structure. Nine independent suppressor mutations were judged to lie in a single suppressor gene, sup-3. Suppression is dominant, but dose dependent, and results in improved locomotion, as well as in an increase in the ability of mutant animals to lay eggs. Mutations in six genes known to affect muscle structure were tested for suppression by representative sup-3 mutations. Alleles of three of the six genes are suppressed, two of which are known to code for thick filament proteins. One suppressor allele was identified as a deletion by genetic criteria. A second case of indirect suppression is not associated with muscle defects, but involves two mutant genes producing uncoordinated phenotypes very similar to one another. As in the first case, suppression is domiant but dose dependent and is not allele specific.

Hashimoto H et al. (1990) J Dermatol "A human case of zoonotic onchocerciasis in Japan."

Akao N, Yoshimura H, Takayasu S, Hashimoto H, Fujiwara S, Murakami I, Takaoka H, Uga S, Kondo K

[J Dermatol, 1990]

A 2-year-old girl living in southwestern Japan had a nodule of 2 months' duration on the left foot. A biopsy from the lesion showed transverse sections of a worm surrounded by granulomatous tissue. The worm was identified as an Onchocerca sp. from the morphological characteristics such as relatively thick cuticles, annular ridges on the cortical layer, and high somatic muscles. Positive serological tests using ELISA for Onchocerca gutturosa and Onchocerca volvulus supported the diagnosis. This was the first case of zoonotic Onchocerca infection detected in Japan. The clinicopathological aspects of zoonotic onchocerciasis of this case were discussed.

Basset D et al. (1991) J Fr Ophtalmol "[Allergic granulomatous nodule of the conjunctiva disclosing onchocerciasis]."

Basset D, D'Hermies F, Lagrange PH, Pouliquen Y

[J Fr Ophtalmol, 1991]

A new case of conjunctival allergic nodule is reported in a Guinean man. This lesion was first described by Ashton and Cook in 1979. Histologically, this nodule consists of amorphous eosinophilic material surrounded by epithelioid and giant cells arranged in a pallisade; some eosinophils are often found in the inflammatory reaction. This lesion usually resolves spontaneously. In documented cases, nematodes and particularly filaria such as Mansonella perstans are usually isolated. Our observation is the first documented case with Onchocerca volvulus. Microfilariae were detected by examination of normal saline containing the biopsy specimen. The new major antifilarial treatment ivermectin was associated.

Bourne HR et al. (1990) Nature "Some signal developments."

Kenyon CJ, Bourne HR, Wrischnik LA

[Nature, 1990]

What molecular signalling machines tell a precursor cell to develop into a specialized structure? In one case, described in three papers, including that by Aroian et al. on page 693 of this issue, these machines turn out to be a receptor tyrosine kinase and a ras protein.

Moss EG (2000) Curr Biol "Non-coding RNAs: Lightning strikes twice."

Moss EG

[Curr Biol, 2000]

A second case has been found of a nematode gene involved in developmental timing that encodes a short, non-coding RNA. Both RNAs are expressed at specific times and appear to repress target genes by interacting with their 3' untranslated regions. A coincidence? Or does this pathway attract small RNA regulators?

Druet-Cabanac M et al. (1999) Am J Epidemiol "Onchocerciasis and epilepsy: a matched case-control study in the Central African Republic."

Tabo A, Bouteille B, Sartoris C, Yaya G, Preux PM, Druet-Cabanac M, Dunand J, Macharia W, Hopkins A, Dumas M, Bernet-Bernady P

[Am J Epidemiol, 1999]

The occurrence of epileptic seizures during onchocercal infestation has been suspected. Epidemiologic studies are necessary to confirm the relation between onchocerciasis and epilepsy. A matched case-control study was conducted in dispensaries of three northwestern towns of the Central African Republic. Each epileptic case was matched against two nonepileptic controls on the six criteria of sex, age (+/-5 years), residence, treatment with ivermectin, date of last ivermectin dose, and the number of ivermectin doses. Onchocerciasis was defined as at least one microfilaria observed in iliac crest skin snip biopsy. A total of 561 subjects (187 cases and 374 controls) were included in the study. Of the epileptics, 39.6% had onchocerciasis, as did 35.8% of the controls. The mean dermal microfilarial load was 26 microfilariae per mg of skin (standard deviation, 42) in the epileptics and 24 microfilariae per mg of skin (standard deviation, 48) in the controls. This matched case-control study found some relation (odds ratio = 1.21, 95% confidence interval 0.81-1.80), although it was nonstatistically significant.

Farkas IJ et al. (2012) PLoS One "Linking proteins to signaling pathways for experiment design and evaluation."

Farkas IJ, Szanto-Varnagy A, Korcsmaros T

[PLoS One, 2012]

Biomedical experimental work often focuses on altering the functions of selected proteins. These changes can hit signaling pathways, and can therefore unexpectedly and non-specifically affect cellular processes. We propose PathwayLinker, an online tool that can provide a first estimate of the possible signaling effects of such changes, e.g., drug or microRNA treatments. PathwayLinker minimizes the users' efforts by integrating protein-protein interaction and signaling pathway data from several sources with statistical significance tests and clear visualization. We demonstrate through three case studies that the developed tool can point out unexpected signaling bias in normal laboratory experiments and identify likely novel signaling proteins among the interactors of known drug targets. In our first case study we show that knockdown of the Caenorhabditis elegans gene cdc-25.1 (meant to avoid progeny) may globally affect the signaling system and unexpectedly bias experiments. In the second case study we evaluate the loss-of-function phenotypes of a less known C. elegans gene to predict its function. In the third case study we analyze GJA1, an anti-cancer drug target protein in human, and predict for this protein novel signaling pathway memberships, which may be sources of side effects. Compared to similar services, a major advantage of PathwayLinker is that it drastically reduces the necessary amount of manual literature searches and can be used without a computational background. PathwayLinker is available at http://PathwayLinker.org. Detailed documentation and source code are available at the website.