Lv Z et al. (2015) Parasitol Res "Genome mining offers a new starting point for parasitology research."

Wu Z, Ji P, Li H, Cai Y, Zhang L, Luo S, Wang H, Lv Z

[Parasitol Res, 2015]

Parasites including helminthes, protozoa, and medical arthropod vectors are a major cause of global infectious diseases, affecting one-sixth of the world's population, which are responsible for enormous levels of morbidity and mortality important and remain impediments to economic development especially in tropical countries. Prevalent drug resistance, lack of highly effective and practical vaccines, as well as specific and sensitive diagnostic markers are proving to be challenging problems in parasitic disease control in most parts of the world. The impressive progress recently made in genome-wide analysis of parasites of medical importance, including trematodes of Clonorchis sinensis, Opisthorchis viverrini, Schistosoma haematobium, S. japonicum, and S. mansoni; nematodes of Brugia malayi, Loa loa, Necator americanus, Trichinella spiralis, and Trichuris suis; cestodes of Echinococcus granulosus, E. multilocularis, and Taenia solium; protozoa of Babesia bovis, B. microti, Cryptosporidium hominis, Eimeria falciformis, E. histolytica, Giardia intestinalis, Leishmania braziliensis, L. donovani, L. major, Plasmodium falciparum, P. vivax, Trichomonas vaginalis, Trypanosoma brucei and T. cruzi; and medical arthropod vectors of Aedes aegypti, Anopheles darlingi, A. sinensis, and Culex quinquefasciatus, have been systematically covered in this review for a comprehensive understanding of the genetic information contained in nuclear, mitochondrial, kinetoplast, plastid, or endosymbiotic bacterial genomes of parasites, further valuable insight into parasite-host interactions and development of promising novel drug and vaccine candidates and preferable diagnostic tools, thereby underpinning the prevention and control of parasitic diseases.

Schierenberg E et al. (1992) Seminars in Developmental Biology "The establishment of embryonic axes and determination of cell fates in embryos of the nematode Caenorhabditis elegans."

Schierenberg E, Strome S

[Seminars in Developmental Biology, 1992]

At the 4-cell stage of the C. elegans embryo, three axes can be defined: anterior-posterior (A-P), dorsal-ventral (D-V), and left-right (L-R). The A-P axis first becomes obvious in the newly fertilized 1-cell embryo. Pronouned cytoplasmic assymmetries arise along the A-P axis during the first cell cycle, after which the zygote undergoes a series of stem cell-like cleavages with an A-P orientation of the mitotic spindle; these cleavages generate several somatic founder cells and a primordial germ cell. The D-V and L-R axes are defined by the direction of spindle rotation as the 2-cell embryo divides into four cells. In contrast to the A-P axis, there do not appear to be cellular asymmetries associated with the D-V and L-R axes, and both axes can easily be reversed by micromanipulation. Thus, with respect to the roles that the embryonic axes serve in cell-fate determination in the early C. elegans embryo, it appears that internally transmitted developmental information is differentially segregated along the A-P axis, but not along the D-V or L-R axes. Instead, D-V and L-R differences in the fates of cells within lineages appear to be dictated by differential

Chen PX et al. (2023) Semin Cell Dev Biol "Mitochondrial stress and aging: Lessons from C. elegans."

Zhang L, Tian Y, Chen D, Chen PX

[Semin Cell Dev Biol, 2023]

Aging is accompanied by a progressive decline in mitochondrial function, which in turn contributes to a variety of age-related diseases. Counterintuitively, a growing number of studies have found that disruption of mitochondrial function often leads to increased lifespan. This seemingly contradictory observation has inspired extensive research into genetic pathways underlying the mitochondrial basis of aging, particularly within the model organism Caenorhabditis elegans. The complex and antagonistic roles of mitochondria in the aging process have altered the view of mitochondria, which not only serve as simple bioenergetic factories but also as signaling platforms for the maintenance of cellular homeostasis and organismal health. Here, we review the contributions of C. elegans to our understanding of mitochondrial function in the aging process over the past decades. In addition, we explore how these insights may promote future research of mitochondrial-targeted strategies in higher organisms to potentially slow aging and delay age-related disease progression.

Best AM et al. (2018) Cell Microbiol "Evasion of phagotrophic predation by protist hosts and innate immunity of metazoan hosts by Legionella pneumophilla."

Best AM, Kwaik YA

[Cell Microbiol, 2018]

Legionella pneumophila is a ubiquitous environmental bacterium that has evolved to infect and proliferate within amoebae and other protists. It is thought that accidental inhalation of contaminated water particles by humans is what has enabled this pathogen to proliferate within alveolar macrophages and cause pneumonia. However, the highly evolved macrophages are equipped more sophisticated innate defense mechanisms than protists, such as the evolution of phagotrophic feeding into phagocytosis with more evolved innate defense processes. Not surprisingly, the majority of proteins involved in phagosome biogenesis (~80%) have origins in the phagotrophy stage of evolution. There are a plethora of highly evolved cellular and innate metazoan processes, not represented in Protist biology, that are modulated by L. pneumophila; including TLR2 signaling, NF-B, apoptotic and inflammatory processes, histone modification, caspases, and the NLRC-Naip5 inflammasomes. Importantly, L. pneumophila infects hemocytes of the invertebrate Galleria mellonella, kill G. mellonella larvae, and proliferate in and kill Drosophila adult flies and Caenorhabditis elegans. Although co-evolution with protist hosts has provided a substantial blueprint for L. pneumophila to infect macrophages, we discuss the further evolutionary aspects of co-evolution of L. pneumophila and its adaptation to modulate various highly evolved innate metazoan processes prior to becoming a human pathogen.

Li Y et al. (2021) Environ Toxicol Chem "Research Advances on the Adverse Effects of Nanomaterials in a Model Organism Caenorhabditis elegans."

Zhong L, Wu T, Shen X, Kong L, Zhang L, Li Y

[Environ Toxicol Chem, 2021]

Along with the rapid development of nanotechnology, the bio-safety assessment of nanotechnology products, including nanomaterials, becomes more and more important. Nematode Caenorhabditis elegans (C. elegans) is a valuable model organism that has been widely used in the field of biology because of their excellent advantages, including low cost, small size, short life span, and highly conservative genomes with vertebral animals. In recent years, the number of nanotoxicological researches using C. elegans is persistently growing. According to these available studies, this review classified the adverse effects of nanomaterials in C. elegans into systematic, cellular and molecular toxicity, and focused on summarizing and analyzing the underlying mechanisms of metal, metal oxide and non-metallic nanomaterials causing toxic effects in C. elegans. The findings in this review provided an insight in further studies on assessing bio-safety of nanomaterials in the ecosystem using C. elegans. This article is protected by copyright. All rights reserved.

Lee SK et al. (2013) Int J Biochem Cell Biol "Dicarbonyl/l-xylulose reductase (DCXR): The multifunctional pentosuria enzyme."

Ahnn J, Lee SK, Son LT, Choi HJ

[Int J Biochem Cell Biol, 2013]

Dicarbonyl/L-xylulose reductase (DCXR) is a highly conserved and phylogenetically widespread enzyme converting L-xylulose into xylitol. It also reduces highly reactive -dicarbonyl compounds, thus performing a dual role in carbohydrate metabolism and detoxification. Enzymatic properties of DCXR from yeast, fungi and mammalian tissue extracts are extensively studied. Deficiency of the DCXR gene causes a human clinical condition called pentosuria and low DCXR activity is implicated in age-related diseases including cancers, diabetes, and human male infertility. While mice provide a model to study clinical condition of these diseases, it is necessary to adopt a physiologically tractable model in which genetic manipulations can be readily achieved to allow the fast genetic analysis of an enzyme with multiple biological roles. Caenorhabditis elegans has been successfully utilized as a model to study DCXR. Here, we discuss the biochemical properties and significance of DCXR activity in various human diseases, and the utility of C. elegans as a research platform to investigate the molecular and cellular mechanism of the DCXR biology.

Basant A et al. (2017) F1000Res "A GAP that Divides."

Glotzer M, Basant A

[F1000Res, 2017]

Cytokinesis in metazoan cells is mediated by an actomyosin-based contractile ring that assembles in response to activation of the small GTPase RhoA. The guanine nucleotide exchange factor that activates RhoA during cytokinesis, ECT-2, is highly regulated. In most metazoan cells, with the notable exception of the early Caenorhabditis elegans embryo, RhoA activation and furrow ingression require the centralspindlin complex. This exception is due to the existence of a parallel pathway for RhoA activation in C. elegans. Centralspindlin contains CYK-4 which contains a predicted Rho family GTPase-activating protein (GAP) domain. The function of this domain has been the subject of considerable debate. Some publications suggest that the GAP domain promotes RhoA activation (for example, Zhang and Glotzer, 2015; Loria, Longhini and Glotzer, 2012), whereas others suggest that it functions to inactivate the GTPase Rac1 (for example, Zhuravlev et al., 2017). Here, we review the mechanisms underlying RhoA activation during cytokinesis, primarily focusing on data in C. elegans. We highlight the importance of considering the parallel pathway for RhoA activation and detailed analyses of cyk-4 mutant phenotypes when evaluating the role of the GAP domain of CYK-4.

Ye Z et al. (2023) Front Cell Dev Biol "Trends in mitochondrial unfolded protein response research from 2004 to 2022: A bibliometric analysis."

Wei Y, Luan Y, Ye Z, Chai R, Shi S, Hu Y, Du Y, Wu H, Zhang L, Xue W

[Front Cell Dev Biol, 2023]

The mitochondrial unfolded protein response (UPR^mt) is a stress response pathway that regulates the expression of mitochondrial chaperones, proteases, and other proteins involved in protein folding and degradation, thereby ensuring proper mitochondrial function. In addition to this critical function, the UPR^mt also plays a role in other cellular processes such as mitochondrial biogenesis, energy metabolism, and cellular signaling. Moreover, the UPR^mt is strongly associated with various diseases. From 2004 to 2022, there has been a lot of interest in UPR^mt. The present study aims to utilized bibliometric tools to assess the genesis, current areas of focus, and research trends pertaining to UPR^mt, thereby highlighting avenues for future research. There were 442 papers discovered to be related to UPR^mt, with the overall number of publications rising yearly. <i>International Journal of Molecular Sciences</i> was the most prominent journal in this field. 2421 authors from 1,402 institutions in 184 nations published studies on UPR^mt. The United States was the most productive country (197 documents). The top three authors were Johan Auwerx, Cole M Haynes, and Dongryeol Ryu. The early focus of UPR^mt is "protein." And then the UPR^mt research shifted from <i>Caenorhabditis elegans</i> back to mammals, and its close link to aging and various diseases. The top emerging research hotspots are neurodegenerative diseases and metabolic diseases. These findings provide the trends and frontiers in the field of UPR^mt, and valuable information for clinicians and scientists to identify new perspectives with potential collaborators and cooperative countries.

Wang X et al. (2020) Front Cell Dev Biol "Diverse Roles of PUF Proteins in Germline Stem and Progenitor Cell Development in C. elegans."

Voronina E, Wang X

[Front Cell Dev Biol, 2020]

Stem cell development depends on post-transcriptional regulation mediated by RNA-binding proteins (RBPs) (Zhang et al., 1997; Forbes and Lehmann, 1998; Okano et al., 2005; Ratti et al., 2006; Kwon et al., 2013). Pumilio and FBF (PUF) family RBPs are highly conserved post-transcriptional regulators that are critical for stem cell maintenance (Wickens et al., 2002; Quenault et al., 2011). The RNA-binding domains of PUF proteins recognize a family of related sequence motifs in the target mRNAs, yet individual PUF proteins have clearly distinct biological functions (Lu et al., 2009; Wang et al., 2018). The <i>C. elegans</i> germline is a simple and powerful model system for analyzing regulation of stem cell development. Studies in <i>C. elegans</i> uncovered specific physiological roles for PUFs expressed in the germline stem cells ranging from control of proliferation and differentiation to regulation of the sperm/oocyte decision. Importantly, recent studies started to illuminate the mechanisms behind PUF functional divergence. This review summarizes the many roles of PUF-8, FBF-1, and FBF-2 in germline stem and progenitor cells (SPCs) and discusses the factors accounting for their distinct biological functions. PUF proteins are conserved in evolution, and insights into PUF-mediated regulation provided by the <i>C. elegans</i> model system are likely relevant for other organisms.

Caffrey CR et al. (2018) PLoS Negl Trop Dis "Cysteine proteases as digestive enzymes in parasitic helminths."

Caffrey CR, Smith D, Dalton JP, Rebello KM, Goupil L

[PLoS Negl Trop Dis, 2018]

We briefly review cysteine proteases (orthologs of mammalian cathepsins B, L, F, and C) that are expressed in flatworm and nematode parasites. Emphasis is placed on enzyme activities that have been functionally characterized, are associated with the parasite gut, and putatively contribute to degrading host proteins to absorbable nutrients [1-4]. Often, gut proteases are expressed as multigene families, as is the case with Fasciola [5] and Haemonchus [6], presumably expanding the range of substrates that can be degraded, not least during parasite migration through host tissues [5]. The application of the free-living planarian and Caenorhabditis elegans as investigative models for parasite cysteine proteases is discussed. Finally, because of their central nutritive contribution, targeting the component gut proteases with small-molecule chemical inhibitors and understanding their utility as vaccine candidates are active areas of research [7].