scholarly journals Guided graph spectral embedding: Application to the C. elegans connectome

2019 ◽  
Vol 3 (3) ◽  
pp. 807-826 ◽  
Author(s):  
Miljan Petrovic ◽  
Thomas A. W. Bolton ◽  
Maria Giulia Preti ◽  
Raphaël Liégeois ◽  
Dimitri Van De Ville
Keyword(s):  
Optimization Criterion ◽  
Energy Concentration ◽  
Nodal Domain ◽  
Local Effects ◽  
Order Processing ◽  
C Elegans ◽  
Importance Weighting ◽  
Spectral Embedding ◽  
Global And Local ◽  
Insight Into

Graph spectral analysis can yield meaningful embeddings of graphs by providing insight into distributed features not directly accessible in nodal domain. Recent efforts in graph signal processing have proposed new decompositions—for example, based on wavelets and Slepians—that can be applied to filter signals defined on the graph. In this work, we take inspiration from these constructions to define a new guided spectral embedding that combines maximizing energy concentration with minimizing modified embedded distance for a given importance weighting of the nodes. We show that these optimization goals are intrinsically opposite, leading to a well-defined and stable spectral decomposition. The importance weighting allows us to put the focus on particular nodes and tune the trade-off between global and local effects. Following the derivation of our new optimization criterion, we exemplify the methodology on the C. elegans structural connectome. The results of our analyses confirm known observations on the nematode’s neural network in terms of functionality and importance of cells. Compared with Laplacian embedding, the guided approach, focused on a certain class of cells (sensory neurons, interneurons, or motoneurons), provides more biological insights, such as the distinction between somatic positions of cells, and their involvement in low- or high-order processing functions.

scholarly journals Global and local contributions to corneal surface curvature: a simple model

2008 ◽  
Vol 67 (1) ◽  
Author(s):  
W. F. Harris
Keyword(s):  
Mathematical Model ◽  
Simple Model ◽  
Tear Film ◽  
Surface Curvature ◽  
Simple Mathematical Model ◽  
Corneal Surface ◽  
Local Effects ◽  
Numerical Example ◽  
Global And Local ◽  
Insight Into

Variations in corneal surface powers reflect variations in the geometry of the cornea.  In particular one can regard corneal surface curvature as a combination of local and global effects.  A simple mathematical model of the cornea is presented which makes use of measurements of the curvature of the anterior and posterior surfaces to decompose the curvature into global and local contributions.  The model gives insight into the source of variations in keratometric measurements, lids and eye turn, perhaps, for global effects and the tear film, perhaps, for local effects.  The model also takes account of the thickness of the cornea.  A numerical example is presented.

Neuropeptide signalling shapes feeding and reproductive behaviours in male C. elegans

2021 ◽  
Author(s):  
Matthew J Gadenne ◽  
Iris Hardege ◽  
Djordji Suleski ◽  
Paris Jaggers ◽  
Isabel Beets ◽  
...  
Keyword(s):  
Synaptic Connectivity ◽  
Male Mating ◽  
Sexually Dimorphic ◽  
C Elegans ◽  
Mating Efficiency ◽  
Sexually Dimorphic Expression ◽  
Pharyngeal Pumping ◽  
Insight Into ◽  
Feeding Behaviours ◽  
Dimorphic Expression

Sexual dimorphism occurs where different sexes of the same species display differences in characteristics not limited to reproduction. For the nematode Caenorhabditis elegans, in which the complete neuroanatomy has been solved for both hermaphrodites and males, sexually dimorphic features have been observed both in terms of the number of neurons and in synaptic connectivity. In addition, male behaviours, such as food-leaving to prioritise searching for mates, have been attributed to neuropeptides released from sex-shared or sex-specific neurons. In this study, we show that the lury-1 neuropeptide gene shows a sexually dimorphic expression pattern; being expressed in pharyngeal neurons in both sexes but displaying additional expression in tail neurons only in the male. We also show that lury-1 mutant animals show sex differences in feeding behaviours, with pharyngeal pumping elevated in hermaphrodites but reduced in males. LURY-1 also modulates male mating efficiency, influencing motor events during contact with a hermaphrodite. Our findings indicate sex-specific roles of this peptide in feeding and reproduction in C. elegans, providing further insight into neuromodulatory control of sexually dimorphic behaviours.

scholarly journals C. elegans provide milk for their young

2020 ◽  
Author(s):  
Carina C. Kern ◽  
StJohn Townsend ◽  
Antoine Salzmann ◽  
Nigel B. Rendell ◽  
Graham W. Taylor ◽  
...  
Keyword(s):  
Sexual Maturity ◽  
Reproductive Effort ◽  
Pacific Salmon ◽  
Resource Transfer ◽  
C Elegans ◽  
Destructive Process ◽  
Severe Pathology ◽  
Intestinal Atrophy ◽  
Insight Into

AbstractAdult C. elegans hermaphrodites exhibit severe senescent pathology that begins to develop within days of reaching sexual maturity (Ezcurra et al., 2018; Garigan et al., 2002; Herndon et al., 2002; Wang et al., 2018). For example, after depletion of self-sperm, intestinal biomass is converted into yolk leading to intestinal atrophy and yolk steatosis (pseudocoelomic lipoprotein pools, PLPs) (Ezcurra et al., 2018; Garigan et al., 2002; Herndon et al., 2002; Sornda et al., 2019). These senescent pathologies are promoted by insulin/IGF-1 signalling (IIS), which also shortens lifespan (Ezcurra et al., 2018; Kenyon, 2010). This pattern of rapid and severe pathology in organs linked to reproduction is reminiscent of semelparous organisms where massive reproductive effort leads to rapid death (reproductive death) as in Pacific salmon (Finch, 1990; Gems et al., 2020). Moreover, destructive conversion of somatic biomass to support reproduction is a hallmark of reproductive death (Gems et al., 2020). Yet arguing against the occurrence of reproductive death in C. elegans is the apparent futility of post-reproductive yolk production. Here we show that this effort is not futile, since post-reproductive mothers vent yolk through their vulva, which is consumed by progeny and supports their growth; thus vented yolk functions as a milk, and C. elegans mothers exhibit a form of lactation. Moreover, IIS promotes lactation, thereby effecting a costly process of resource transfer from postreproductive mothers to offspring. These results support the view that C. elegans hermaphrodites exhibit reproductive death involving a self-destructive process of lactation that is promoted by IIS. They also provide new insight into how the strongly life-shortening effects of IIS in C. elegans evolved.

scholarly journals The Caenorhabditis elegans DEG-3/DES-2 Channel Is a Betaine-Gated Receptor Insensitive to Monepantel

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 312
Author(s):  
Tina V. A. Hansen ◽  
Heinz Sager ◽  
Céline E. Toutain ◽  
Elise Courtot ◽  
Cédric Neveu ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Parasitic Nematode ◽  
Nematode Species ◽  
Xenopus Laevis Oocytes ◽  
Allosteric Modulators ◽  
C Elegans ◽  
Electrode Voltage ◽  
Insight Into

Natural plant compounds, such as betaine, are described to have nematocidal properties. Betaine also acts as a neurotransmitter in the free-living model nematode Caenorhabditis elegans, where it is required for normal motility. Worm motility is mediated by nicotinic acetylcholine receptors (nAChRs), including subunits from the nematode-specific DEG-3 group. Not all types of nAChRs in this group are associated with motility, and one of these is the DEG-3/DES-2 channel from C. elegans, which is involved in nociception and possibly chemotaxis. Interestingly, the activity of DEG-3/DES-2 channel from the parasitic nematode of ruminants, Haemonchus contortus, is modulated by monepantel and its sulfone metabolite, which belong to the amino-acetonitrile derivative anthelmintic drug class. Here, our aim was to advance the pharmacological knowledge of the DEG-3/DES-2 channel from C. elegans by functionally expressing the DEG-3/DES-2 channel in Xenopus laevis oocytes and using two-electrode voltage-clamp electrophysiology. We found that the DEG-3/DES-2 channel was more sensitive to betaine than ACh and choline, but insensitive to monepantel and monepantel sulfone when used as direct agonists and as allosteric modulators in co-application with betaine. These findings provide important insight into the pharmacology of DEG-3/DES-2 from C. elegans and highlight the pharmacological differences between non-parasitic and parasitic nematode species.

scholarly journals Systematic characterization and genetic interaction analysis of adhesins in Candida albicans virulence

2020 ◽  
Author(s):  
Sierra Rosiana ◽  
Liyang Zhang ◽  
Grace H. Kim ◽  
Alexey V. Revtovich ◽  
Arjun Sukumaran ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Genetic Interaction ◽  
Interaction Analysis ◽  
Genetic Interactions ◽  
Fungal Virulence ◽  
C Elegans ◽  
Adhesin Proteins ◽  
Insight Into

AbstractCandida albicans is a microbial fungus that exists as a commensal member of the human microbiome and an opportunistic pathogen. Cell surface-associated adhesin proteins play a crucial role in C. albicans’ ability to undergo cellular morphogenesis, develop robust biofilms, colonize, and cause infection in a host. However, a comprehensive analysis of the role and relationships between these adhesins has not been explored. We previously established a CRISPR-based platform for efficient generation of single- and double-gene deletions in C. albicans, which was used to construct a library of 144 mutants, comprising 12 unique adhesin genes deleted singly, or in every possible combination of double deletions. Here, we exploit this adhesin mutant library to explore the role of adhesin proteins in C. albicans virulence. We perform a comprehensive, high-throughput screen of this library, using Caenorhabditis elegans as a simplified model host system, which identified mutants critical for virulence and significant genetic interactions. We perform follow-up analysis to assess the ability of high- and low-virulence strains to undergo cellular morphogenesis and form biofilms in vitro, as well as to colonize the C. elegans host. We further perform genetic interaction analysis to identify novel significant negative genetic interactions between adhesin mutants, whereby combinatorial perturbation of these genes significantly impairs virulence, more than expected based on virulence of the single mutant constituent strains. Together, this yields important new insight into the role of adhesins, singly and in combinations, in mediating diverse facets of virulence of this critical fungal pathogen.SummaryCandida albicans is a human fungal pathogen and cause of life-threatening systemic infections. Cell surface-associated adhesins play a central role in this pathogen’s ability to establish infection. Here, we provide a comprehensive analysis of adhesin factors, and their role in fungal virulence. Exploiting a high-throughput workflow, we screened an adhesin mutant library using C. elegans as a simple model host, and identified mutants and genetic interactions involved in virulence. We found that adhesin mutants are impaired in in vitro pathogenicity, irrespective of their virulence. Together, this work provides new insight into the role of adhesin factors in mediating fungal virulence.

scholarly journals Neuropeptides and Behaviors: How Small Peptides Regulate Nervous System Function and Behavioral Outputs

2021 ◽  
Vol 14 ◽  
Author(s):  
Umer Saleem Bhat ◽  
Navneet Shahi ◽  
Siju Surendran ◽  
Kavita Babu
Keyword(s):  
Nervous System ◽  
Behavioral Plasticity ◽  
Environmental Changes ◽  
Sensory Information ◽  
Synaptic Activity ◽  
Small Peptides ◽  
C Elegans ◽  
Wide Range ◽  
Nervous System Function ◽  
Insight Into

One of the reasons that most multicellular animals survive and thrive is because of the adaptable and plastic nature of their nervous systems. For an organism to survive, it is essential for the animal to respond and adapt to environmental changes. This is achieved by sensing external cues and translating them into behaviors through changes in synaptic activity. The nervous system plays a crucial role in constantly evaluating environmental cues and allowing for behavioral plasticity in the organism. Multiple neurotransmitters and neuropeptides have been implicated as key players for integrating sensory information to produce the desired output. Because of its simple nervous system and well-established neuronal connectome, C. elegans acts as an excellent model to understand the mechanisms underlying behavioral plasticity. Here, we critically review how neuropeptides modulate a wide range of behaviors by allowing for changes in neuronal and synaptic signaling. This review will have a specific focus on feeding, mating, sleep, addiction, learning and locomotory behaviors in C. elegans. With a view to understand evolutionary relationships, we explore the functions and associated pathophysiology of C. elegans neuropeptides that are conserved across different phyla. Further, we discuss the mechanisms of neuropeptidergic signaling and how these signals are regulated in different behaviors. Finally, we attempt to provide insight into developing potential therapeutics for neuropeptide-related disorders.

scholarly journals A Novel Method for Predicting Disease-Associated LncRNA-MiRNA Pairs Based on the Higher-Order Orthogonal Iteration

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zhanwei Xuan ◽  
Xiang Feng ◽  
Jingwen Yu ◽  
Pengyao Ping ◽  
Haochen Zhao ◽  
...  
Keyword(s):  
Higher Order ◽  
System Level ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Great Insight ◽  
Novel Method ◽  
Global And Local ◽  
Novel Model ◽  
Insight Into ◽  
Orthogonal Iteration

A lot of research studies have shown that many complex human diseases are associated not only with microRNAs (miRNAs) but also with long noncoding RNAs (lncRNAs). However, most of the current existing studies focus on the prediction of disease-related miRNAs or lncRNAs, and to our knowledge, until now, there are few literature studies reported to pay attention to the study of impact of miRNA-lncRNA pairs on diseases, although more and more studies have shown that both lncRNAs and miRNAs play important roles in cell proliferation and differentiation during the recent years. The identification of disease-related genes provides great insight into the underlying pathogenesis of diseases at a system level. In this study, a novel model called PADLMHOOI was proposed to predict potential associations between diseases and lncRNA-miRNA pairs based on the higher-order orthogonal iteration, and in order to evaluate its prediction performance, the global and local LOOCV were implemented, respectively, and simulation results demonstrated that PADLMHOOI could achieve reliable AUCs of 0.9545 and 0.8874 in global and local LOOCV separately. Moreover, case studies further demonstrated the effectiveness of PADLMHOOI to infer unknown disease-related lncRNA-miRNA pairs.

scholarly journals Shapelet Discovery by Lazy Time Series Classification

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Wei Zhang ◽  
Zhihai Wang ◽  
Jidong Yuan ◽  
Shilei Hao
Keyword(s):  
Time Series ◽  
Training Dataset ◽  
Class Label ◽  
Considerable Research ◽  
Evaluation Dataset ◽  
Differential Ability ◽  
Global And Local ◽  
Insight Into ◽  
Specific Evaluation ◽  
Feature Frequency

As a representation of discriminative features, the time series shapelet has recently received considerable research interest. However, most shapelet-based classification models evaluate the differential ability of the shapelet on the whole training dataset, neglecting characteristic information contained in each instance to be classified and the classwise feature frequency information. Hence, the computational complexity of feature extraction is high, and the interpretability is inadequate. To this end, the efficiency of shapelet discovery is improved through a lazy strategy fusing global and local similarities. In the prediction process, the strategy learns a specific evaluation dataset for each instance, and then the captured characteristics are directly used to progressively reduce the uncertainty of the predicted class label. Moreover, a shapelet coverage score is defined to calculate the discriminability of each time stamp for different classes. The experimental results show that the proposed method is competitive with the benchmark methods and provides insight into the discriminative features of each time series and each type in the data.

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