The oscillating Mucin-type protein DPY-6 has a conserved role in nematode mouth and cuticle formation

Genetics ◽  
2021 ◽  
Author(s):  
Shuai Sun ◽  
Tobias Theska ◽  
Hanh Witte ◽  
Erik J Ragsdale ◽  
Ralf J Sommer

Abstract Nematodes show an extraordinary diversity of mouth structures and strikingly different feeding strategies, which has enabled an invasion of all ecosystems. However, nearly nothing is known about the structural and molecular architecture of the nematode mouth (stoma). Pristionchus pacificus is an intensively studied nematode that exhibits unique life history traits, including predation, teeth-like denticle formation, and mouth-form plasticity. Here, we used a large-scale genetic screen to identify genes involved in mouth formation. We identified Ppa-dpy-6 to encode a Mucin-type hydrogel-forming protein that is macroscopically involved in the specification of the cheilostom, the anterior part of the mouth. We used a recently developed protocol for geometric morphometrics of miniature animals to characterize these defects further and found additional defects that affect mouth form, shape, and size resulting in an overall malformation of the mouth. Additionally, Ppa-dpy-6 is shorter than wild-type with a typical Dumpy phenotype, indicating a role in the formation of the external cuticle. This concomitant phenotype of the cheilostom and cuticle provides the first molecular support for the continuity of these structures and for the separation of the cheilostom from the rest of the stoma. In C. elegans, dpy-6 was an early mapping mutant but its molecular identity was only determined during genome-wide RNAi screens and not further investigated. Strikingly, geometric morphometric analysis revealed previously unrecognized cheilostom and gymnostom defects in Cel-dpy-6 mutants. Thus, the Mucin-type protein DPY-6 represents to the best of our knowledge, the first protein involved in nematode mouth formation with a conserved role in cuticle deposition. This study opens new research avenues to characterize the molecular composition of the nematode mouth, which is associated with extreme ecological diversification.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lukas Schmauder ◽  
Klaus Richter

AbstractNematode development is characterized by progression through several larval stages. Thousands of genes were found in large scale RNAi-experiments to block this development at certain steps, two of which target the molecular chaperone HSP-90 and its cofactor UNC-45. Aiming to define the cause of arrest, we here investigate the status of nematodes after treatment with RNAi against hsp-90 and unc-45 by employing an in-depth transcriptional analysis of the arrested larvae. To identify misregulated transcriptional units, we calculate and validate genome-wide coexpression cliques covering the entire nematode genome. We define 307 coexpression cliques and more than half of these can be related to organismal functions by GO-term enrichment, phenotype enrichment or tissue enrichment analysis. Importantly, hsp-90 and unc-45 RNAi induce or repress many of these cliques in a coordinated manner, and then several specifically regulated cliques are observed. To map the developmental state of the arrested nematodes we define the expression behaviour of each of the cliques during development from embryo to adult nematode. hsp-90 RNAi can be seen to arrest development close to the L4 larval stage with further deviations in daf-16 regulated genes. unc-45 RNAi instead leads to arrested development at young adult stage prior to the programmatic downregulation of sperm-cell specific genes. In both cases processes can be defined to be misregulated upon depletion of the respective chaperone. With most of the defined gene cliques showing concerted behaviour at some stage of development from embryo to late adult, the “clique map” together with the clique-specific GO-terms, tissue and phenotype assignments will be a valuable tool in understanding concerted responses on the genome-wide level in Caenorhabditis elegans.


Author(s):  
Ron Avi Astor ◽  
Rami Benbenisthty

Since 2005, the bullying, school violence, and school safety literatures have expanded dramatically in content, disciplines, and empirical studies. However, with this massive expansion of research, there is also a surprising lack of theoretical and empirical direction to guide efforts on how to advance our basic science and practical applications of this growing scientific area of interest. Parallel to this surge in interest, cultural norms, media coverage, and policies to address school safety and bullying have evolved at a remarkably quick pace over the past 13 years. For example, behaviors and populations that just a decade ago were not included in the school violence, bullying, and school safety discourse are now accepted areas of inquiry. These include, for instance, cyberbullying, sexting, social media shaming, teacher–student and student–teacher bullying, sexual harassment and assault, homicide, and suicide. Populations in schools not previously explored, such as lesbian, gay, bisexual, transgender, and queer students and educators and military- and veteran-connected students, become the foci of new research, policies, and programs. As a result, all US states and most industrialized countries now have a complex quilt of new school safety and bullying legislation and policies. Large-scale research and intervention funding programs are often linked to these policies. This book suggests an empirically driven unifying model that brings together these previously distinct literatures. This book presents an ecological model of school violence, bullying, and safety in evolving contexts that integrates all we have learned in the 13 years, and suggests ways to move forward.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephan Fischer ◽  
Marc Dinh ◽  
Vincent Henry ◽  
Philippe Robert ◽  
Anne Goelzer ◽  
...  

AbstractDetailed whole-cell modeling requires an integration of heterogeneous cell processes having different modeling formalisms, for which whole-cell simulation could remain tractable. Here, we introduce BiPSim, an open-source stochastic simulator of template-based polymerization processes, such as replication, transcription and translation. BiPSim combines an efficient abstract representation of reactions and a constant-time implementation of the Gillespie’s Stochastic Simulation Algorithm (SSA) with respect to reactions, which makes it highly efficient to simulate large-scale polymerization processes stochastically. Moreover, multi-level descriptions of polymerization processes can be handled simultaneously, allowing the user to tune a trade-off between simulation speed and model granularity. We evaluated the performance of BiPSim by simulating genome-wide gene expression in bacteria for multiple levels of granularity. Finally, since no cell-type specific information is hard-coded in the simulator, models can easily be adapted to other organismal species. We expect that BiPSim should open new perspectives for the genome-wide simulation of stochastic phenomena in biology.


2021 ◽  
Vol 9 (2) ◽  
pp. 310
Author(s):  
Masayuki Hashimoto ◽  
Yi-Fen Ma ◽  
Sin-Tian Wang ◽  
Chang-Shi Chen ◽  
Ching-Hao Teng

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.


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