scholarly journals Conditional depletion reveals temporal requirements for the oscillating transcription factor NHR-23/NR1F1 in C. elegans larval progression

2021 ◽  
Author(s):  
Londen C Johnson ◽  
Joseph D Aguilera ◽  
Max T Levenson ◽  
Andreas D Rechtsteiner ◽  
An A Vo ◽  
...  
Keyword(s):  
Large Scale ◽  
Nuclear Hormone Receptor ◽  
C Elegans ◽  
Physiological Processes ◽  
Morphological Defects ◽  
Steroid Hormone Signaling ◽  
Important Regulator ◽  
Time Courses ◽  
Many Core ◽  
Oscillatory Network

Nematode molting is a remarkable process where the animals must essentially build a new epidermis underneath the old skin and then rapidly shed the old skin. The study of molting provides a gateway into the developmental program of many core cellular and physiological processes, such as oscillatory gene expression, coordinated intracellular trafficking, steroid hormone signaling, developmental timing, and extracellular remodeling. The nuclear hormone receptor NHR-23/NR1F1 is an important regulator of molting. Imaging and western blot time-courses revealed oscillatory NHR-23::GFP expression in the epithelium that closely followed the reported mRNA expression. Timed depletion experiments using the auxin-inducible degron system revealed that NHR-23/NR1F1 depletion early in a given larval stage caused animals to arrest with only weak molting defects, whereas later depletion resulted in highly penetrant severe molting and morphological defects. This larval arrest was independent of insulin signaling. Despite the weakly penetrant molting defects following early NHR-23/NR1F1 depletion, the epidermal barrier was defective suggesting that NHR-23/NR1F1 is necessary for establishing or maintaining this barrier. NHR-23/NR1F1 coordinates the expression of factors involved in molting, lipid transport/metabolism, and remodeling of the apical extracellular matrix. We propose that NHR-23/NR1F1 is a regulator in a recently discovered large-scale gene oscillatory network coordinating rhythmic skin regeneration.

scholarly journals ECHO: an application for detection and analysis of oscillators identifies metabolic regulation on genome-wide circadian output

2019 ◽  
Vol 36 (3) ◽  
pp. 773-781 ◽  
Author(s):  
Hannah De los Santos ◽  
Emily J Collins ◽  
Catherine Mann ◽  
April W Sagan ◽  
Meaghan S Jankowski ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Large Scale ◽  
R Package ◽  
Supplementary Information ◽  
Genome Wide ◽  
Important Regulator ◽  
Time Courses ◽  
Synthetic Datasets ◽  
Genome Scale ◽  
The Impact

Abstract Motivation Time courses utilizing genome scale data are a common approach to identifying the biological pathways that are controlled by the circadian clock, an important regulator of organismal fitness. However, the methods used to detect circadian oscillations in these datasets are not able to accommodate changes in the amplitude of the oscillations over time, leading to an underestimation of the impact of the clock on biological systems. Results We have created a program to efficaciously identify oscillations in large-scale datasets, called the Extended Circadian Harmonic Oscillator application, or ECHO. ECHO utilizes an extended solution of the fixed amplitude oscillator that incorporates the amplitude change coefficient. Employing synthetic datasets, we determined that ECHO outperforms existing methods in detecting rhythms with decreasing oscillation amplitudes and in recovering phase shift. Rhythms with changing amplitudes identified from published biological datasets revealed distinct functions from those oscillations that were harmonic, suggesting purposeful biologic regulation to create this subtype of circadian rhythms. Availability and implementation ECHO’s full interface is available at https://github.com/delosh653/ECHO. An R package for this functionality, echo.find, can be downloaded at https://CRAN.R-project.org/package=echo.find. Supplementary information Supplementary data are available at Bioinformatics online.

Research on highly parallel embedded control system design and implementation method

Impact ◽  
2019 ◽  
Vol 2019 (10) ◽  
pp. 44-46
Author(s):  
Masato Edahiro ◽  
Masaki Gondo
Keyword(s):  
Computer Architecture ◽  
Intelligent Systems ◽  
Large Scale ◽  
General Purpose ◽  
Heterogeneous Structure ◽  
Single Chip ◽  
Powertrain Control ◽  
Processing Power ◽  
Hardware Description ◽  
Many Core

The pace of technology's advancements is ever-increasing and intelligent systems, such as those found in robots and vehicles, have become larger and more complex. These intelligent systems have a heterogeneous structure, comprising a mixture of modules such as artificial intelligence (AI) and powertrain control modules that facilitate large-scale numerical calculation and real-time periodic processing functions. Information technology expert Professor Masato Edahiro, from the Graduate School of Informatics at the Nagoya University in Japan, explains that concurrent advances in semiconductor research have led to the miniaturisation of semiconductors, allowing a greater number of processors to be mounted on a single chip, increasing potential processing power. 'In addition to general-purpose processors such as CPUs, a mixture of multiple types of accelerators such as GPGPU and FPGA has evolved, producing a more complex and heterogeneous computer architecture,' he says. Edahiro and his partners have been working on the eMBP, a model-based parallelizer (MBP) that offers a mapping system as an efficient way of automatically generating parallel code for multi- and many-core systems. This ensures that once the hardware description is written, eMBP can bridge the gap between software and hardware to ensure that not only is an efficient ecosystem achieved for hardware vendors, but the need for different software vendors to adapt code for their particular platforms is also eliminated.

scholarly journals Iron Acquisition of Urinary Tract Infection Escherichia coli Involves Pathogenicity in Caenorhabditis elegans

2021 ◽  
Vol 9 (2) ◽  
pp. 310
Author(s):  
Masayuki Hashimoto ◽  
Yi-Fen Ma ◽  
Sin-Tian Wang ◽  
Chang-Shi Chen ◽  
Ching-Hao Teng
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Caenorhabditis Elegans ◽  
Large Scale ◽  
Iron Acquisition ◽  
Infection Model ◽  
High Throughput Analysis ◽  
E Coli ◽  
C Elegans ◽  
Tract Infections

Uropathogenic Escherichia coli (UPEC) is a major bacterial pathogen that causes urinary tract infections (UTIs). The mouse is an available UTI model for studying the pathogenicity; however, Caenorhabditis elegans represents as an alternative surrogate host with the capacity for high-throughput analysis. Then, we established a simple assay for a UPEC infection model with C. elegans for large-scale screening. A total of 133 clinically isolated E. coli strains, which included UTI-associated and fecal isolates, were applied to demonstrate the simple pathogenicity assay. From the screening, several virulence factors (VFs) involved with iron acquisition (chuA, fyuA, and irp2) were significantly associated with high pathogenicity. We then evaluated whether the VFs in UPEC were involved in the pathogenicity. Mutants of E. coli UTI89 with defective iron acquisition systems were applied to a solid killing assay with C. elegans. As a result, the survival rate of C. elegans fed with the mutants significantly increased compared to when fed with the parent strain. The results demonstrated, the simple assay with C. elegans was useful as a UPEC infectious model. To our knowledge, this is the first report of the involvement of iron acquisition in the pathogenicity of UPEC in a C. elegans model.

scholarly journals Large-scale RNAi screens identify novel genes that interact with the C. elegans retinoblastoma pathway as well as splicing-related components with synMuv B activity

2007 ◽  
Vol 7 (1) ◽  
pp. 30 ◽  
Author(s):  
Julian Ceron ◽  
Jean-François Rual ◽  
Abha Chandra ◽  
Denis Dupuy ◽  
Marc Vidal ◽  
...  
Keyword(s):  
Large Scale ◽  
Novel Genes ◽  
C Elegans

Frequent Germline Mutations and Somatic Repeat Instability in DNA Mismatch-Repair-Deficient Caenorhabditis elegans

Genetics ◽  
2002 ◽  
Vol 161 (2) ◽  
pp. 651-660
Author(s):  
Marcel Tijsterman ◽  
Joris Pothof ◽  
Ronald H A Plasterk
Keyword(s):  
Caenorhabditis Elegans ◽  
Mismatch Repair ◽  
Large Scale ◽  
Somatic Tissue ◽  
Repeat Instability ◽  
Dna Mismatch ◽  
C Elegans ◽  
Colon Cancers ◽  
Dna Repeat ◽  
Female Germline

Abstract Mismatch-repair-deficient mutants were initially recognized as mutation-prone derivatives of bacteria, and later mismatch repair deficiency was found to predispose humans to colon cancers (HNPCC). We generated mismatch-repair-deficient Caenorhabditis elegans by deleting the msh-6 gene and analyzed the fidelity of transmission of genetic information to subsequent generations. msh-6-defective animals show an elevated level of spontaneous mutants in both the male and female germline; also repeated DNA tracts are unstable. To monitor DNA repeat instability in somatic tissue, we developed a sensitive system, making use of heat-shock promoter-driven lacZ transgenes, but with a repeat that puts this reporter gene out of frame. In genetic msh-6-deficient animals lacZ+ patches are observed as a result of somatic repeat instability. RNA interference by feeding wild-type animals dsRNA homologous to msh-2 or msh-6 also resulted in somatic DNA instability, as well as in germline mutagenesis, indicating that one can use C. elegans as a model system to discover genes involved in maintaining DNA stability by large-scale RNAi screens.

Caenorhabditis elegansPlexinA, PLX-1, interacts with transmembrane semaphorins and regulates epidermal morphogenesis

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2053-2063 ◽  
Author(s):  
Takashi Fujii ◽  
Fumi Nakao ◽  
Yukimasa Shibata ◽  
Go Shioi ◽  
Eiji Kodama ◽  
...  
Keyword(s):  
Rna Interference ◽  
Morphological Changes ◽  
Expression System ◽  
Transmembrane Proteins ◽  
Axonal Guidance ◽  
Heterologous Expression System ◽  
C Elegans ◽  
Morphological Defects ◽  
Epidermal Morphogenesis ◽  
Null Mutants

The plexin family transmembrane proteins are putative receptors for semaphorins, which are implicated in the morphogenesis of animal embryos, including axonal guidance. We have generated and characterized putative null mutants of the C. elegans plexinA gene, plx-1. plx-1 mutants exhibited morphological defects: displacement of ray 1 and discontinuous alae. The epidermal precursors for the affected organs were aberrantly arranged in the mutants, and a plx-1::gfp transgene was expressed in these epidermal precursor cells as they underwent dynamic morphological changes. Suppression of C. elegans transmembrane semaphorins, Ce-Sema-1a and Ce-Sema-1b, by RNA interference caused a displacement of ray 1 similar to that of plx-1 mutants, whereas mutants for the Ce-Sema-2a/mab-20 gene, which encodes a secreted-type semaphorin, exhibited phenotypes distinct from those of plx-1 mutants. A heterologous expression system showed that Ce-Sema-1a, but not Ce-Sema-2a, physically bound to PLX-1. Our results indicate that PLX-1 functions as a receptor for transmembrane-type semaphorins, and, though Ce-Sema-2a and PLX-1 both play roles in the regulation of cellular morphology during epidermal morphogenesis, they function rather independently.

Efficient Vector Partitioning Algorithms for Graph Clustering

2020 ◽  
Vol 1 (2) ◽  
pp. 101-123
Author(s):  
Hiroaki Shiokawa ◽  
Yasunori Futamura
Keyword(s):  
Social Networks ◽  
Large Scale ◽  
Clustering Algorithm ◽  
Ground Truth ◽  
Graph Clustering ◽  
Mining Communities ◽  
Fine Grained ◽  
Efficient Vector ◽  
Public Datasets ◽  
Many Core

This paper addressed the problem of finding clusters included in graph-structured data such as Web graphs, social networks, and others. Graph clustering is one of the fundamental techniques for understanding structures present in the complex graphs such as Web pages, social networks, and others. In the Web and data mining communities, the modularity-based graph clustering algorithm is successfully used in many applications. However, it is difficult for the modularity-based methods to find fine-grained clusters hidden in large-scale graphs; the methods fail to reproduce the ground truth. In this paper, we present a novel modularity-based algorithm, \textit{CAV}, that shows better clustering results than the traditional algorithm. The proposed algorithm employs a cohesiveness-aware vector partitioning into the graph spectral analysis to improve the clustering accuracy. Additionally, this paper also presents a novel efficient algorithm \textit{P-CAV} for further improving the clustering speed of CAV; P-CAV is an extension of CAV that utilizes the thread-based parallelization on a many-core CPU. Our extensive experiments on synthetic and public datasets demonstrate the performance superiority of our approaches over the state-of-the-art approaches.

An integrated view of innate immune mechanisms in C. elegans

2021 ◽  
Author(s):  
Benjamin W. Harding ◽  
Jonathan J. Ewbank
Keyword(s):  
Innate Immune ◽  
Innate Immune Responses ◽  
Fully Integrated ◽  
Immune Mechanisms ◽  
C Elegans ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Model Animal ◽  
Molecular Specificity ◽  
Simple Notion

The simple notion ‘infection causes an immune response' is being progressively refined as it becomes clear that immune mechanisms cannot be understood in isolation, but need to be considered in a more global context with other cellular and physiological processes. In part, this reflects the deployment by pathogens of virulence factors that target diverse cellular processes, such as translation or mitochondrial respiration, often with great molecular specificity. It also reflects molecular cross-talk between a broad range of host signalling pathways. Studies with the model animal C. elegans have uncovered a range of examples wherein innate immune responses are intimately connected with different homeostatic mechanisms, and can influence reproduction, ageing and neurodegeneration, as well as various other aspects of its biology. Here we provide a short overview of a number of such connections, highlighting recent discoveries that further the construction of a fully integrated view of innate immunity.

scholarly journals GABA receptors differentially regulate life span and health span in C. elegans through distinct downstream mechanisms

2019 ◽  
Vol 317 (5) ◽  
pp. C953-C963 ◽  
Author(s):  
Fengling Yuan ◽  
Jiejun Zhou ◽  
Lingxiu Xu ◽  
Wenxin Jia ◽  
Lei Chun ◽  
...  
Keyword(s):  
Life Span ◽  
Gaba Receptors ◽  
Health Span ◽  
Gaba A ◽  
Inhibitory Neurotransmitter ◽  
C Elegans ◽  
Physiological Processes ◽  
Gaba Signaling ◽  
Neuronal Functions

GABA, a prominent inhibitory neurotransmitter, is best known to regulate neuronal functions in the nervous system. However, much less is known about the role of GABA signaling in other physiological processes. Interestingly, recent work showed that GABA signaling can regulate life span via a metabotropic GABAB receptor in Caenorhabditis elegans. However, the role of other types of GABA receptors in life span has not been clearly defined. It is also unclear whether GABA signaling regulates health span. Here, using C. elegans as a model, we systematically interrogated the role of various GABA receptors in both life span and health span. We find that mutations in four different GABA receptors extend health span by promoting resistance to stress and pathogen infection and that two such receptor mutants also show extended life span. Different GABA receptors engage distinct transcriptional factors to regulate life span and health span, and even the same receptor regulates life span and health span via different transcription factors. Our results uncover a novel, profound role of GABA signaling in aging in C. elegans, which is mediated by different GABA receptors coupled to distinct downstream effectors.

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