Iwasaki Y et al. (2004) Bull Math Biol "Stochastic formulation for a partial neural circuit of C. elegans."

Gomi S, Iwasaki Y

[Bull Math Biol, 2004]

We present a stochastic formulation for a partial neural circuit of Caenorhabditis elegans. This study is concerned with how to reduce the degree of freedom in a large neural circuit. In the presented formulation, neurons in the whole neural circuit are divided into two complementary groups. One is the neurons which are mainly associated with a certain behavior, and the other is the remaining neurons of C. elegans. In an ordinary study on a partial neural circuit, the influence of the latter (the remaining neurons) on the former (the associated neurons) is completely neglected. In the presented formulation, however, the influence is expressed by a stochastic variable. The structure of the ensemble for the stochastic variable is appropriately evaluated by the neural connectivity of C. elegans since the neural connectivity of C. elegans has been completely determined. In this way, the degree of freedom is effectively reduced. We apply the presented formulation to determine the synaptic signs in the touch sensitivity circuit of C. elegans. The synaptic signs are determined to satisfy the locomotory behaviors in C. elegans. We find that the influence of the remaining neurons on the touch sensitivity circuit is important to determine the synaptic signs.

Iwasaki Y et al. (2000) Japanese Worm Meeting "Study of Excitatory and Inhibitory Synaptic Connections in Neural Circuit for Touch-induced and Tap Responses"

Osana Y, Gomi S, Iwasaki Y

[Japanese Worm Meeting, 2000]

In order to predict the signs (excitatory or inhibitory) of connections between neurons, numerical studies are performed on the neural circuit of C.elegans for the touch-induced and the tap response. Neurons are modeled simply as McCulloch-Pitts neurons. Among all possible ways of assigning the signs for each connection, we select out the networks which satisfy the correct neural input-output relations of both touch-induced and tap responses.Experimental knowledge on the effects of laser ablation of neurons are also used as conditions for the selection of the networks. By examining the average structure of the remained (selected) networks, some of the signs of connections in the networks may be unambiguously predicted. These results are compared to the results of the study which use the process of learning for producing the neural networks with correct input-output relations.

Yuishi Iwasaki (2005) International Worm Meeting "How to model and study a partial neural circuit of C. elegans?"

Yuishi Iwasaki

[International Worm Meeting, 2005]

In a numerical study of a partial neural circuit for a certain behavior, there are two general problems. (i) To simulate a certain behavior of a worm, we usually adopt only the neurons which are mainly associated with its behavior. The influence of the remaining neurons of C. elegans is completely neglected (closed circuit). However, the behavior is realized by the whole neural circuit with an external stimulation (open circuit). There is no guarantee that a numerical result in the closed partial neural circuit is consistent with that in the open circuit. This is a problem in neural modeling. (ii) To assign a behavioral criterion to the neural circuit, we usually analyze a stationary state of the neuron. That is, all the membrane potentials Vi(t) are dVi(t)/dt=0 in the neural circuit. However, it is not clear that the neuron is in a stationary state or not when a worm is moving. This is a problem in analyzing the neural circuit.To solve the former problem (i), a mathematical formulation has been proposed for the McCulloch-Pitts model (Iwasaki, Y. and Gomi, S. (2004). Bulletin of Mathematical Biology, 66, 727-743). The influence of the remaining neurons on the associated neurons is formulated as the external noise for a partial neural circuit. Since the neural connectivity of C. elegans has been completely determined, the stochastic property of the external noise is appropriately evaluated by the neural connectivity. Thus the degree of freedom is effectively reduced in neural modeling. However, the McCulloch-Pitts model is not the most suitable model to represent a real nervous system of C. elegans since the McCulloch-Pitts neuron is activated stepwisely. In this presentation, a mathematical formulation for a more physiologically adequate neural model is proposed. Furthermore, this formulation is applied to behavioral neural circuits of C. elegans. Considering the latter problem (ii), the dynamics of the neural circuit is analyzed. This work was supported by JSPS (No. RFTF-96I00102) and MEXT (No. 16740239).

Matsuoka T et al. (2008) J Theor Biol "Simulation of C. elegans thermotactic behavior in a linear thermal gradient using a simple phenomenological motility model."

Matsuoka T, Gomi S, Shingai R

[J Theor Biol, 2008]

The nematode Caenorhabditis elegans has been reported to exhibit thermotaxis, a sophisticated behavioral response to temperature. However, there appears to be some inconsistency among previous reports. The results of population-level thermotaxis investigations suggest that C. elegans can navigate to the region of its cultivation temperature from nearby regions of higher or lower temperature. However, individual C. elegans nematodes appear to show only cryophilic tendencies above their cultivation temperature. A Monte-Carlo style simulation using a simple individual model of C. elegans provides insight into clarifying apparent inconsistencies among previous findings. The simulation using the thermotaxis model that includes the cryophilic tendencies, isothermal tracking and thermal adaptation was conducted. As a result of the random walk property of locomotion of C. elegans, only cryophilic tendencies above the cultivation temperature result in population-level thermophilic tendencies. Isothermal tracking, a period of active pursuit of an isotherm around regions of temperature near prior cultivation temperature, can strengthen the tendencies of these worms to gather around near-cultivation-temperature regions. A statistical index, the thermotaxis (TTX) L-skewness, was introduced and was useful in analyzing the population-level thermotaxis of model worms.

Vinci CR et al. (2007) J Biol Chem "Recognition of age-damaged (R,S)-adenosyl-L-methionine by two methyltransferases in the yeast Saccharomyces cerevisiae."

Vinci CR, Clarke SG

[J Biol Chem, 2007]

The biological methyl donor, S adenosylmethionine (AdoMet), can exist in two diastereoisomeric states with respect to its sulfonium ion. The "S" configuration, (S,S)AdoMet, is the only form that is produced enzymatically as well as the only form used in almost all biological methylation reactions. Under physiological conditions, however, the sulfonium ion can spontaneously racemize to the "R" form, producing (R,S)AdoMet. As of yet, (R,S)AdoMet has no known physiological function and may inhibit cellular reactions. In this study, two enzymes have been found in Saccharomyces cerevisiae that are capable of recognizing (R,S)AdoMet and using it to methylate homocysteine to form methionine. These enzymes are the products of the SAM4 and MHT1 genes, previously identified as homocysteine methyltransferases dependent upon AdoMet and S-methylmethionine respectively. We find here that Sam4 recognizes both (S,S) and (R,S)AdoMet, but its activity is much higher with the R,S form. Mht1 reacts with only the R,S form of AdoMet while no activity is seen with the S,S form. R,S-specific homocysteine methyltransferase activity is also shown here to occur in extracts of Arabidopsis thaliana, Drosophila melanogaster, and Caenorhabditis elegans, but has not been detected in several tissue extracts of Mus musculus. Such activity may function to prevent the accumulation of (R,S)AdoMet in these organisms.

Fanning S et al. (2018) Mol Cell "Lipidomic Analysis of -Synuclein Neurotoxicity Identifies Stearoyl CoA Desaturase as a Target for Parkinson Treatment."

Termine D, Becuwe M, Hofbauer HF, Barrasa MI, Pincus D, Imberdis T, Selkoe D, Freyzon Y, Srinivasan S, Soldner F, Nuber S, Sandoe J, Haque A, Welte MA, Clish CB, Terry-Kantor E, Jaenisch R, Kohlwein SD, Fanning S, Dettmer U, Walther TC, Kim TE, Farese RV, Landgraf D, Baru V, Noble T, Lou Y, Lindquist S, Newby G, Ho GPH, Ramalingam N

[Mol Cell, 2018]

In Parkinson's disease (PD), -synuclein (S) pathologically impacts the brain, a highly lipid-rich organ. We investigated how alterations in S or lipid/fattyacid homeostasis affect each other. Lipidomic profiling of human S-expressing yeast revealed increases in oleic acid (OA, 18:1), diglycerides, and triglycerides. These findings were recapitulated in rodent and human neuronal models of S dyshomeostasis (overexpression; patient-derived triplication or E46K mutation; E46K mice). Preventing lipid droplet formation or augmenting OA increased S yeast toxicity; suppressing the OA-generating enzyme stearoyl-CoA-desaturase (SCD) was protective. Genetic or pharmacological SCD inhibition ameliorated toxicity in S-overexpressing rat neurons. In a C.elegans model, SCD knockout prevented S-induced dopaminergic degeneration. Conversely, we observed detrimental effects of OA on S homeostasis: in human neural cells, excess OA caused S inclusion formation, which was reversed by SCD inhibition. Thus, monounsaturated fatty acid metabolism is pivotal for S-induced neurotoxicity, and inhibiting SCD represents a novel PD therapeutic approach.

Vandecandelaere I et al. (2017) PLoS One "Metabolic activity, urease production, antibiotic resistance and virulence in dual species biofilms of Staphylococcus epidermidis and Staphylococcus aureus."

Coenye T, Van Nieuwerburgh F, Deforce D, Vandecandelaere I

[PLoS One, 2017]

In this paper, the metabolic activity in single and dual species biofilms of Staphylococcus epidermidis and Staphylococcus aureus isolates was investigated. Our results demonstrated that there was less metabolic activity in dual species biofilms compared to S. aureus biofilms. However, this was not observed if S. aureus and S. epidermidis were obtained from the same sample. The largest effect on metabolic activity was observed in biofilms of S. aureus Mu50 and S. epidermidis ET-024. A transcriptomic analysis of these dual species biofilms showed that urease genes and genes encoding proteins involved in metabolism were downregulated in comparison to monospecies biofilms. These results were subsequently confirmed by phenotypic assays. As metabolic activity is related to acid production, the pH in dual species biofilms was slightly higher compared to S. aureus Mu50 biofilms. Our results showed that S. epidermidis ET-024 in dual species biofilms inhibits metabolic activity of S. aureus Mu50, leading to less acid production. As a consequence, less urease activity is required to compensate for low pH. Importantly, this effect was biofilm-specific. Also S. aureus Mu50 genes encoding virulence-associated proteins (Spa, SplF and Dps) were upregulated in dual species biofilms compared to monospecies biofilms and using Caenorhabditis elegans infection assays, we demonstrated that more nematodes survived when co-infected with S. epidermidis ET-024 and S. aureus mutants lacking functional spa, splF or dps genes, compared to nematodes infected with S. epidermidis ET-024 and wild- type S. aureus. Finally, S. epidermidis ET-024 genes encoding resistance to oxacillin, erythromycin and tobramycin were upregulated in dual species biofilms and increased resistance was subsequently confirmed. Our data indicate that both species in dual species biofilms of S. epidermidis and S. aureus influence each other's behavior, but additional studies are required necessary to elucidate the exact mechanism(s) involved.

Kamp F et al. (2010) EMBO J "Inhibition of mitochondrial fusion by -synuclein is rescued by PINK1, Parkin and DJ-1."

Kamp F, Winklhofer KF, Giese A, Lutz AK, Brunner B, Wender N, Hegermann J, Haass C, Eimer S, Bartels T, Beyer K, Exner N, Nuscher B

[EMBO J, 2010]

Aggregation of -synuclein (S) is involved in the pathogenesis of Parkinson's disease (PD) and a variety of related neurodegenerative disorders. The physiological function of S is largely unknown. We demonstrate with in vitro vesicle fusion experiments that S has an inhibitory function on membrane fusion. Upon increased expression in cultured cells and in Caenorhabditis elegans, S binds to mitochondria and leads to mitochondrial fragmentation. In C. elegans age-dependent fragmentation of mitochondria is enhanced and shifted to an earlier time point upon expression of exogenous S. In contrast, siRNA-mediated downregulation of S results in elongated mitochondria in cell culture. S can act independently of mitochondrial fusion and fission proteins in shifting the dynamic morphologic equilibrium of mitochondria towards reduced fusion. Upon cellular fusion, S prevents fusion of differently labelled mitochondrial populations. Thus, S inhibits fusion due to its unique membrane interaction. Finally, mitochondrial fragmentation induced by expression of S is rescued by coexpression of PINK1, parkin or DJ-1 but not the PD-associated mutations PINK1 G309D and parkin 1-79 or by DJ-1 C106A.

Vandecandelaere I et al. (2014) Pathog Dis "Protease production by Staphylococcus epidermidis and its effect on Staphylococcus aureus biofilms."

Depuydt P, Coenye T, Vandecandelaere I, Nelis HJ

[Pathog Dis, 2014]

Due to the resistance of Staphylococcus aureus to several antibiotics, treatment of S. aureus infections is often difficult. As an alternative to conventional antibiotics, the field of bacterial interference is investigated. Staphylococcus epidermidis produces a serine protease (Esp) which inhibits S. aureus biofilm formation and which degrades S. aureus biofilms. In this study, we investigated the protease production of 114 S. epidermidis isolates, obtained from biofilms on endotracheal tubes (ET). Most of the S. epidermidis isolates secreted a mixture of serine, cysteine and metalloproteases. We found a link between high protease production by S. epidermidis and the absence of S. aureus in ET biofilms obtained from the same patient. Treating S. aureus biofilms with the supernatant (SN) of the most active protease producing S. epidermidis isolates resulted in a significant biomass decrease compared to untreated controls, while the number of metabolically active cells was not affected. The effect on the biofilm biomass was mainly due to serine proteases. Staphylococcus aureus biofilms treated with the SN of protease producing S. epidermidis were thinner with almost no extracellular matrix. An increased survival of Caenorhabditis elegans, infected with S. aureus Mu50, was observed when the SN of protease positive S. epidermidis was added.

El Mouridi, Sonia et al. (2021) MicroPubl Biol

AlHarbi, Sarah, El Mouridi, Sonia, Frkjr-Jensen, Christian

[MicroPubl Biol, 2021]

For El Mouridi, S; AlHarbi, S; Frkjr-Jensen, C (2021). A histamine-gated channel is an efficient negative selection marker for C. elegans transgenesis. microPublication Biology. 10.17912/micropub.biology.000349.