scholarly journals Recurrent Neural Networks with Interpretable Cells Predict and Classify Worm Behaviour

2017 ◽  
Author(s):  
Kezhi Li ◽  
Avelino Javer ◽  
Eric E. Keaveny ◽  
Andre E.X. Brown

AbstractAn important goal in behaviour analytics is to connect disease state or genome variation with observable differences in behaviour. Despite advances in sensor technology and imaging, informative behaviour quantification remains challenging. The nematode worm C. elegans provides a unique opportunity to test analysis approaches because of its small size, compact nervous system, and the availability of large databases of videos of freely behaving animals with known genetic differences. Despite its relative simplicity, there are still no reports of generative models that can capture essential differences between even well-described mutant strains. Here we show that a multilayer recurrent neural network (RNN) can produce diverse behaviours that are difficult to distinguish from real worms’ behaviour and that some of the artificial neurons in the RNN are interpretable and correlate with observable features such as body curvature, speed, and reversals. Although the RNN is not trained to perform classification, we find that artificial neuron responses provide features that perform well in worm strain classification.

Author(s):  
Brandon Lam

Cancer is one of the most prevalent and deadly diseases in today's society, affecting millions of people around the globe. Uncontrolled cell division and migration which are two of the six major hallmarks of cancer have been studied extensively in vitro, however in vivo these hallmarks are not well understood. We used the Caenorhabditis elegans nematode worm as our model organism in order to study these two hallmarks. In unfavorable environmental conditions such as starvation, C. elegans can enter a developmental arrest in where certain cell metabolism ceases to continue, this stage is known as L1 arrest. Normally in L1 arrested worms, there are 2 distinct Q neuroblast cells which are precursors of sensory and interneurons that do not divide and migrate. However, when we mutate certain genes, we noticed that the two Q neuroblasts inappropriately divided and migrated, this suggests that we have identified a good model to study uncontrolled cell division and migration. We have already found one gene that when mutated, results in the Q neuroblasts inappropriately dividing and migrating at L1 arrest, now we are looking for other mutated genes that can cause this phenotype, this ultimately allows us to identify new mechanisms that cause an increase risk in cancer.​


2008 ◽  
Vol 294 (1) ◽  
pp. C333-C344 ◽  
Author(s):  
K. Nehrke ◽  
Jerod Denton ◽  
William Mowrey

Defecation in the nematode worm Caenorhabditis elegans is a highly rhythmic behavior that is regulated by a Ca2+ wave generated in the 20 epithelial cells of the intestine, in part through activation of the inositol 1,4,5-trisphosphate receptor. Execution of the defecation motor program (DMP) can be modified by external cues such as nutrient availability or mechanical stimulation. To address the likelihood that environmental regulation of the DMP requires integrating distinct cellular and organismal processes, we have developed a method for studying coordinate Ca2+ oscillations and defecation behavior in intact, freely behaving animals. We tested this technique by examining how mutations in genes known to alter Ca2+ handling [including egl-8/phospholipase C (PLC)-β, kqt-3/KCNQ1, sca-1/sarco(endo)plasmic reticulum Ca2+ ATPase, and unc-43/Ca2+-CaMKII] contribute to shaping the Ca2+ wave and asked how Ca2+ wave dynamics in the mutant backgrounds altered execution of the DMP. Notably, we find that Ca2+ waves in the absence of PLCβ initiate ectopically, often traveling in reverse, and fail to trigger a complete DMP. These results suggest that the normal supremacy of the posterior intestinal cells is not obligatory for Ca2+ wave occurrence but instead helps to coordinate the DMP. Furthermore, we present evidence suggesting that an underlying pacemaker appears to oscillate at a faster frequency than the defecation cycle and that arrhythmia may result from uncoupling the pacemaker from the DMP rather than from disrupting the pacemaker itself. We also show that chronic elevations in Ca2+ have limited influence on the defecation period but instead alter the interval between successive steps of the DMP. Finally, our results demonstrate that it is possible to assess Ca2+ dynamics and muscular contractions in a completely unrestrained model organism.


2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.


2019 ◽  
Vol 19 (4) ◽  
pp. 428-438 ◽  
Author(s):  
Nívea P. de Sá ◽  
Ana P. Pôssa ◽  
Pilar Perez ◽  
Jaqueline M.S. Ferreira ◽  
Nayara C. Fonseca ◽  
...  

<p>Background: The increasing incidence of invasive forms of candidiasis and resistance to antifungal therapy leads us to seek new and more effective antifungal compounds. </P><P> Objective: To investigate the antifungal activity and toxicity as well as to evaluate the potential targets of 2- cyclohexylidenhydrazo-4-phenyl-thiazole (CPT) in Candida albicans. </P><P> Methods: The antifungal activity of CPT against the survival of C. albicans was investigated in Caenorhabditis elegans. Additionally, we determined the effect of CPT on the inhibition of C. albicans adhesion capacity to buccal epithelial cells (BECs), the toxicity of CPT in mammalian cells, and the potential targets of CPT in C. albicans. </P><P> Results: CPT exhibited a minimum inhibitory concentration (MIC) value of 0.4-1.9 µg/mL. Furthermore, CPT at high concentrations (>60 x MIC) showed no or low toxicity in HepG2 cells and <1% haemolysis in human erythrocytes. In addition, CPT decreased the adhesion capacity of yeasts to the BECs and prolonged the survival of C. elegans infected with C. albicans. Analysis of CPT-treated cells showed that their cell wall was thinner than that of untreated cells, especially the glucan layer. We found that there was a significantly lower quantity of 1,3-β-D-glucan present in CPT-treated cells than that in untreated cells. Assays performed on several mutant strains showed that the MIC value of CPT was high for its antifungal activity on yeasts with defective 1,3-β-glucan synthase. </P><P> Conclusion: In conclusion, CPT appears to target the cell wall of C. albicans, exhibits low toxicity in mammalian cells, and prolongs the survival of C. elegans infected with C. albicans.</p>


2012 ◽  
Vol 206 (1) ◽  
pp. 78-82 ◽  
Author(s):  
Maohua Zheng ◽  
Pengxiu Cao ◽  
Jiong Yang ◽  
X.Z. Shawn Xu ◽  
Zhaoyang Feng

2006 ◽  
Vol 950 ◽  
Author(s):  
Shuang Fang Lim ◽  
Robert Riehn ◽  
Chih-Kuan Tung ◽  
David Tank ◽  
William S. Ryu ◽  
...  

ABSTRACTWe have synthesized rare-earth doped sub-10 nm diameter upconverting yttrium oxide based nanophosphors by flame spray pyrolysis. We have investigated the emitted visible fluorescence of the sub-10nm nanophosphors under both infrared excitation and electron excitation, and observed comparable narrow band emission spectra. The viability of the nanoparticles for biological imaging was confirmed by imaging the digestive system of the nematode worm C. elegans in the upconversion mode. We have surface functionalized the nanophosphors making them suitable for bio labeling.


2014 ◽  
Vol 204 (4) ◽  
pp. 507-522 ◽  
Author(s):  
Vincent Gaggioli ◽  
Eva Zeiser ◽  
David Rivers ◽  
Charles R. Bradshaw ◽  
Julie Ahringer ◽  
...  

Cyclin-dependent kinase (CDK) plays a vital role in proliferation control across eukaryotes. Despite this, how CDK mediates cell cycle and developmental transitions in metazoa is poorly understood. In this paper, we identify orthologues of Sld2, a CDK target that is important for DNA replication in yeast, and characterize SLD-2 in the nematode worm Caenorhabditis elegans. We demonstrate that SLD-2 is required for replication initiation and the nuclear retention of a critical component of the replicative helicase CDC-45 in embryos. SLD-2 is a CDK target in vivo, and phosphorylation regulates the interaction with another replication factor, MUS-101. By mutation of the CDK sites in sld-2, we show that CDK phosphorylation of SLD-2 is essential in C. elegans. Finally, using a phosphomimicking sld-2 mutant, we demonstrate that timely CDK phosphorylation of SLD-2 is an important control mechanism to allow normal proliferation in the germline. These results determine an essential function of CDK in metazoa and identify a developmental role for regulated SLD-2 phosphorylation.


2020 ◽  
Author(s):  
Maria Gravato-Nobre ◽  
Jonathan Hodgkin ◽  
Petros Ligoxygakis

ABSTRACTThe nematode worm Caenorhabditis elegans depends on microbes in decaying vegetation as its food source. To survive in an environment rich in opportunistic pathogens, C. elegans has evolved an epithelial defence system where surface-exposed tissues such as epidermis, pharynx, intestine, vulva and hindgut have the capacity of eliciting appropriate immune defences to acute gut infection. However, it is unclear how the worm responds to chronic intestinal infections. To this end, we have surveyed C. elegans mutants that are involved in inflammation, immunity and longevity to find their phenotypes during chronic infection. Worms that grew in a monoculture of the natural pathogen Microbacterium nematophilum (CBX102 strain) had a reduced lifespan and health span. This was independent of intestinal colonisation as both CBX102 and the derived avirulent strain UV336 were early persistent colonisers. In contrast, long-lived daf-2 mutants were resistant to chronic infection, showing reduced colonisation and a higher age-dependent vigour. In fact, UV336 acted as a probiotic in daf-2, showing a lifespan extension beyond OP50, the E. coli strain used for laboratory C. elegans culture. Longevity and vigour of daf-2 mutants growing on CBX102 was dependent on the FOXO orthologue DAF-16. Since the DAF-2/DAF-16 axis is present in most metazoans this suggests an evolutionary conserved host mechanism to modify a pathogen to a commensal.


Genetics ◽  
1981 ◽  
Vol 97 (2) ◽  
pp. 281-305 ◽  
Author(s):  
Joseph G Culotti ◽  
Gunter Von Ehrenstein ◽  
Marilyn R Culotti ◽  
Richard L Russell

ABSTRACT In Johnson et al. (1981), the Caenorhabditis elegans mutant strain PR1000, homozygous for the ace-1 mutation p1000, is shown to be deficient in the class A subset of acetylcholinesterases, which comprises approximately one-half of the total C. elegans acetylcholinesterase activity. Beginning with this strain, we have isolated 487 new behavioral and morphological mutant strains. Two of these, independently derived, lack approximately 98% of the wild-type acetylcholinesterase activity and share the same specific uncoordinated phenotype; both move forward in a slow and uncoordinated manner, and when mechanically stimulated to induce reversal, both hypercontract and become temporarily paralyzed. In addition to the ace-1 mutation, both strains also harbor recessive mutations in the same newly identified gene, ace-2, which maps to chromosome I and is therefore not linked to ace-1. Gene dosage experiments suggest that ace-2 is a structural gene for the remaining class B acetylcholinesterases, which are not affected by ace-1. —The uncoordinated phenotype of the newly isolated, doubly mutant strains depends on both the ace-1 and ace-2 mutations; homozygosity for either mutation alone produces normally coordinated animals. This result implies functional overlap of the acetylcholinesterases controlled by ace-1 and ace-2, perhaps at common synapses. Consistent with this, light microscopic histochemical staining of permeabilized whole mounts indicates some areas of possible spatial overlap of these acetylcholinesterases (nerve ring, longitudinal nerve cords). In addition, there is at least one area where only ace-2-controlled acetylcholinesterase activity appears (pharyngeo-intestinal valve).


Author(s):  
Rashid Anasari

This study survey and proves this effectiveness connected with artificial neural networks (ANNs) as an alternative approach in the tourism research. The learning utilizes the travel industry in the Japan being a method for estimating need to exhibit the solicitation. The outcome reveals the use of ANNs in tourism research might perhaps result in better quotations when it comes to prediction bias and accuracy. Even more applications of ANNs in the context of tourism demand examination is needed to establish and validate the effects. An ANN is based on a collection of connected units or nodes called artificial neurons, which loosely model the neurons in a biological brain. Each connection, like the synapses in a biological brain, can transmit a signal to other neurons. An artificial neuron that receives a signal then processes it and can signal neurons connected to it.


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