White J (2018) Development "Obituary: John Sulston (1942-2018)."

White J

[Development, 2018]

John Sulston, a pioneer in the developmental studies of the nematode <i>C. elegans</i> who went on to spearhead the sequencing of the genome of this organism and ultimately the human genome, died on 6th March 2018, shortly after being diagnosed with stomach cancer. Here, I reflect on John's life and work, with a particular focus on his time working on the developmental genetics and lineage of <i>C. elegans</i><i>.</i>

Shen P et al. (2017) Annu Rev Food Sci Technol "Caenorhabditis elegans: A Convenient In Vivo Model for Assessing the Impact of Food Bioactive Components on Obesity, Aging, and Alzheimer's Disease."

Zheng J, Shen P, Yue Y, Park Y

[Annu Rev Food Sci Technol, 2017]

Caenorhabditis elegans is a small free-living nematode that lives in temperate soil environments. It has been widely employed as an animal model in research involving obesity, aging, and neurodegenerative diseases, including Alzheimer's disease, because of its various advantages, such as small size, large number of progeny production, completely sequenced genome, and short life span, over traditional animal models of vertebrates. These benefits contribute to an ideal research model organism. In this review, we provide an introduction to C. elegans and its applications in obesity, aging, and Alzheimer's disease studies, with the aim of stimulating scientists to use C. elegans as an experimental model in various fields of research. Expected final online publication date for the Annual Review of Food Science and Technology Volume 9 is March 25, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Shintoku Y et al. (2005) J Parasitol "Strongyloides ratti infection in the large intestine of wild rats, Rattus norvegicus."

Kimura E, Hasegawa H, Shintoku Y, Kondo S, Islam MZ, Kadosaka T, Itoh M

[J Parasitol, 2005]

The large intestine of a rat has been neglected almost completely as a site of Strongyloides sp. infection. We reported that adult Strongyloides ratti remained in the large intestine for more than 80 days, producing more number of infective larvae than small intestine adults, and therefore hypothesized that parasitism in this site could be a survival strategy. In wild rats, however, no study has focused on large intestine infections of Strongyloides. The present study revealed that 32.4% of 68 wild rats, Rattus norvegicus, had the infection of S. ratti in the large intestine, with an average of 4.7 worms. These worms harbored normal eggs in the uterus. In a laboratory experiment with S. ratti and Wister rats, daily output of infective larvae by 4.7 females in the large intestine was estimated to be 4,638.4, suggesting that a few parasites could play a role in the parasite transmission. Five species of nematode found in the wild rats showed seasonality in infection intensity, with highest intensities in March-May. The number of S. ratti in the large intestine was also highest in these months.

King KC et al. (2016) ISME J "Rapid evolution of microbe-mediated protection against pathogens in a worm host."

Ford SA, Brockhurst MA, Haldenby S, Vasieva O, Betts A, King KC, Frost CL, Horsburgh MJ, Hurst GD, Paterson S

[ISME J, 2016]

Microbes can defend their host against virulent infections, but direct evidence for the adaptive origin of microbe-mediated protection is lacking. Using experimental evolution of a novel, tripartite interaction, we demonstrate that mildly pathogenic bacteria (Enterococcus faecalis) living in worms (Caenorhabditis elegans) rapidly evolved to defend their animal hosts against infection by a more virulent pathogen (Staphylococcus aureus), crossing the parasitism-mutualism continuum. Host protection evolved in all six, independently selected populations in response to within-host bacterial interactions and without direct selection for host health. Microbe-mediated protection was also effective against a broad spectrum of pathogenic S. aureus isolates. Genomic analysis implied that the mechanistic basis for E. faecalis-mediated protection was through increased production of antimicrobial superoxide, which was confirmed by biochemical assays. Our results indicate that microbes living within a host may make the evolutionary transition to mutualism in response to pathogen attack, and that microbiome evolution warrants consideration as a driver of infection outcome.The ISME Journal advance online publication, 15 March 2016; doi:10.1038/ismej.2015.259.

Wardell B et al. (2006) Br J Pharmacol "Residues in the first transmembrane domain of the Caenorhabditis elegans GABA(A) receptor confer sensitivity to the neurosteroid pregnenolone sulfate."

Rutar T, Marik PS, Bamber BA, Piper D, Wardell B, Jorgensen EM

[Br J Pharmacol, 2006]

The GABA(A) receptor is a target of endogenous and synthetic neurosteroids. Little is known about the residues required for neurosteroid action on GABA(A) receptors. We have investigated pregnenolone sulfate (PS) inhibition of the Caenorhabditis elegans UNC-49 GABA receptor, a close homolog of the mammalian GABA(A) receptor.The UNC-49 locus encodes two GABA receptor subunits, UNC-49B and UNC-49C. UNC-49C is sensitive to PS but UNC-49B is not sensitive. By analyzing chimeric receptors and receptors containing site-directed mutations, we identified two regions required for PS inhibition.Four residues in the first transmembrane domain are required for the majority of the sensitivity to PS, but a charged extracellular residue at the end of the M2 helix also plays a role. Strikingly, mutation of one additional M1 residue reverses the effect of PS from an inhibitor to an enhancer of receptor function.Mutating the M1 domain had little effect on sensitivity to the inhibitor picrotoxin, suggesting that these residues may mediate neurosteroid action specifically, and not allosteric regulation in general.British Journal of Pharmacology advance online publication, 20 March 2006; doi:10.1038/sj.bjp.0706719.

Zarlenga DS et al. (2009) Vet Parasitol "From parasite genomes to one healthy world: Are we having fun yet?"

Gasbarre LC, Zarlenga DS

[Vet Parasitol, 2009]

In 1990, the Human Genome Sequencing Project was established. This laid the ground work for an explosion of sequence data that has since followed. As a result of this effort, the first complete genome of an animal, Caenorhabditis elegans was published in 1998. The sequence of Drosophila melanogaster was made available in March, 2000 and in the following year, working drafts of the human genome were generated with the completed sequence (92%) being released in 2003. Recent advancements and next-generation technologies have made sequencing common place and have infiltrated every aspect of biological research, including parasitology. To date, sequencing of 32 apicomplexa and 24 nematode genomes are either in progress or near completion, and over 600k nematode EST and 200k apicomplexa EST submissions fill the databases. However, the winds have shifted and efforts are now refocusing on how best to store, mine and apply these data to problem solving. Herein we tend not to summarize existing X-omics datasets or present new technological advances that promise future benefits. Rather, the information to follow condenses up-to-date-applications of existing technologies to problem solving as it relates to parasite research. Advancements in non-parasite systems are also presented with the proviso that applications to parasite research are in the making.

Rahman MM et al. (2020) Foodborne Pathog Dis "Prevalence, Antimicrobial Resistance, and Pathogenic Potential of Enterotoxigenic and Enteropathogenic Escherichia coli Associated with Acute Diarrheal Patients in Tangail, Bangladesh."

Rahman MM, Shibly AZ, Sakib N, Kar A, Hasan MN, Ahmed P, Zohora FT

[Foodborne Pathog Dis, 2020]

In this study, the prevalence and antimicrobial resistance of enterotoxigenic <i>Escherichia coli</i> (ETEC) and enteropathogenic <i>Escherichia coli</i> (EPEC) were investigated. Altogether 100 stool samples were collected from diarrheal patients attending the Sheikh Hasina Medical College and Hospital, Tangail, Bangladesh, during the period from March 1 to May 30, 2018. <i>In vivo</i> pathogenic potential of ETEC and EPEC using a <i>Caenorhabditis elegans</i> infection model was investigated. Among 100 diarrheal patients, 31% were positive for both ETEC and EPEC strains, 23% were <i>lt</i> positive for ETEC strains, and 8% were <i>bfpA</i> positive for EPEC strains. It was detected that 82.60%, 65.21%, 73.91%, 78.26%, 47.82%, 60.86%, and 47.82% of ETEC strains were resistant to amoxicillin-clavulanic acid (AMC), tetracycline (TE), nalidixic acid (NA), azithromycin, ciprofloxacin, ampicillin (AMP), and erythromycin (E), respectively. Whereas it was detected that 87.5% strains were resistant to AMC, AMP, and E, 75% were resistant to TE and NA, respectively. Both strains developed multidrug resistance to commonly prescribed antibiotics. EPEC showed higher pathogenicity than ETEC as 67.75% and 60% of <i>C. elegans</i> died after 18h postinfection with EPEC and ETEC, respectively. The high rate of antimicrobial resistance of EPEC and ETEC highlights the necessity for the prudent use of antimicrobials in Bangladesh.

Fonte V et al. (2002) Proc Natl Acad Sci U S A "Interaction of intracellular beta amyloid peptide with chaperone proteins."

Taft A, Link CD, Friedman D, Fonte V, Fluet A, Kapulkin V

[Proc Natl Acad Sci U S A, 2002]

Communicated by William B. Wood, University of Colorado, Boulder, CO, May 24, 2002 (received for review March 22, 2002) Expression of the human ss amyloid peptide (Ass) in transgenic Caenorhabditis elegans animals can lead to the formation of intracellular immunoreactive deposits as well as the formation of intracellular amyloid. We have used this model to identify proteins that interact with intracellular Ass in vivo. Mass spectrometry analysis of proteins that specifically coimmunoprecipitate with Ass has identified six likely chaperone proteins: two members of the HSP70 family, three alphaB-crystallin-related small heat shock proteins (HSP-16s), and a putative ortholog of a mammalian small glutamine-rich tetratricopeptide repeat-containing protein proposed to regulate HSP70 function. Quantitative reverse transcription--PCR analysis shows that the small heat shock proteins are also transcriptionally induced by Ass expression. Immunohistochemistry demonstrates that HSP-16 protein closely colocalizes with intracellular Ass in this model. Transgenic animals expressing a nonaggregating Ass variant, a single-chain Ass dimer, show an altered pattern of coimmunoprecipitating proteins and an altered cellular distribution of HSP-16. Double-stranded RNA inhibition of R05F9.10, the putative C. elegans ortholog of the human small glutamine-rich tetratricopeptide-repeat-containing protein (SGT), results in suppression of toxicity associated with Ass expression. These results suggest that chaperone function can play a role in modulating intracellular Ass metabolism and toxicity.

Stergiou L et al. (2007) Cell Death Differ "The nucleotide excision repair pathway is required for UV-C-induced apoptosis in Caenorhabditis elegans."

Stergiou L, Sendoel A, Hengartner MO, Doukoumetzidis K

[Cell Death Differ, 2007]

Ultraviolet (UV) radiation is a mutagen of major clinical importance in humans. UV-induced damage activates multiple signaling pathways, which initiate DNA repair, cell cycle arrest and apoptosis. To better understand these pathways, we studied the responses to UV-C light (254 nm) of germ cells in Caenorhabditis elegans. We found that UV activates the same cellular responses in worms as in mammalian cells. Both UV-induced apoptosis and cell cycle arrest were completely dependent on the p53 homolog CEP-1, the checkpoint proteins HUS-1 and CLK-2, and the checkpoint kinases CHK-2 and ATL-1 (the C. elegans homolog of ataxia telangiectasia and Rad3-related); ATM-1 (ataxia telangiectasia mutated-1) was also required, but only at low irradiation doses. Importantly, mutation of genes encoding nucleotide excision repair pathway components severely disrupted both apoptosis and cell cycle arrest, suggesting that these genes not only participate in repair, but also signal the presence of damage to downstream components of the UV response pathway that we delineate here. Our study suggests that whereas DNA damage response pathways are conserved in metazoans in their general outline, there is significant evolution in the relative importance of individual checkpoint genes in the response to specific types of DNA damage.Cell Death and Differentiation advance online publication, 9 March 2007; doi:10.1038/sj.cdd.4402115.

Carraro U (2020) Eur J Transl Myol "Thirty years of translational research in Mobility Medicine: Collection of abstracts of the 2020 Padua Muscle Days."

Carraro U

[Eur J Transl Myol, 2020]

More than half a century of skeletal muscle research is continuing at Padua University (Italy) under the auspices of the Interdepartmental Research Centre of Myology (CIR-Myo), the European Journal of Translational Myology (EJTM) and recently also with the support of the A&amp;CM-C Foundation for Translational Myology, Padova, Italy. The Volume 30(1), 2020 of the EJTM opens with the collection of abstracts for the conference &quot;2020 Padua Muscle Days: Mobility Medicine 30 years of Translational Research&quot;. This is an international conference that will be held between March 18-21, 2020 in Euganei Hills and Padova in Italy. The abstracts are excellent examples of translational research and of the multidimensional approaches that are needed to classify and manage (in both the acute and chronic phases) diseases of Mobility that span from neurologic, metabolic and traumatic syndromes to the biological process of aging. One of the typical aim of Physical Medicine and Rehabilitation is indeed to reduce pain and increase mobility enough to enable impaired persons to walk freely, garden, and drive again. The excellent contents of this Collection of Abstracts reflect the high scientific caliber of researchers and clinicians who are eager to present their results at the PaduaMuscleDays. A series of EJTM Communications will also add to this preliminary evidence.