Steinbaugh, Michael J. et al. (2013) International Worm Meeting "Regulation of SKN-1/Nrf by the germline longevity pathway."

Robida-Stubbs, Stacey, Operana, Theresa, Steinbaugh, Michael J., Raghavan, Prashant, Narasimhan, Sri Devi, Blackwell, T. Keith

[International Worm Meeting, 2013]

In C. elegans, a reduction in germline stem cell (GSC) number increases lifespan and stress resistance through a longevity pathway that seems to be distinct from those related to nutrient sensing and metabolism (e.g. insulin/IGF-1 signaling, the TOR pathway, mitochondrial function, and dietary restriction). The GSC pathway is a tissue non-autonomous regulator of longevity that is known to involve the transcription factors DAF-16, DAF-12, and NHR-80 in the intestine. We recently determined that the transcription factor SKN-1 (Nrf in mammals) is also regulated by this pathway. The germline can be removed through laser ablation or genetic disruption of the Notch ortholog GLP-1. Using skn-1(zu135), skn-1 RNAi, and temperature-sensitive glp-1(bn18) mutants, we determined that skn-1 is required for lifespan extension associated with GSC removal. In contrast to DAF-16, SKN-1 is also required for the associated increase in oxidative stress resistance (e.g. sodium arsenite, tert-butylhydroperoxide). We found that SKN-1 accumulates in intestinal nuclei when GSC number is reduced, and that this is partially dependent upon KRI-1, an ankryin repeat protein implicated in regulation of DAF-16 by this pathway. Using qRT-PCR and analysis of transcriptional reporters, we determined that multiple SKN-1 target genes (e.g. gst-4, gcs-1, nit-1, and F20D6.11) are transcriptionally upregulated in germline-deficient animals in a SKN-1-dependent manner. This distinctive longevity pathway provides an exciting example of environmental sensing and signaling from the reproductive stem cell niche. Current efforts are aimed at understanding how the GSC pathway regulates SKN-1, and identifying processes controlled by SKN-1 in this context.

Colonnello A et al. (2020) Neurotox Res "Correction to: Comparing the Neuroprotective Effects of Caffeic Acid in Rat Cortical Slices and Caenorhabditis elegans: Involvement of Nrf2 and SKN-1 Signaling Pathways."

Tunez I, Rubio-Lopez LC, Aguilera-Portillo G, Silva-Palacios A, Evaristo-Priego Y, Santamaria A, Galvan-Arzate S, Cortez-Nunez S, Aschner M, Rangel-Lopez E, Chen P, Colonnello A, Robles-Banuelos B, Garcia-Contreras R

[Neurotox Res, 2020]

One of the authors has incorrect family name spelling in the original article_. Michael Ashner should read as Michael Aschner.

Hengartner MO et al. (1992) Worm Breeder's Gazette "unc-50, a Gene Required for Acetylcholine Receptor Function, Encodes an Unfamiliar Protein"

Horvitz HR, Tsung N, Hengartner MO, Lewis JA

[Worm Breeder's Gazette, 1992]

unc-50, a gene requiired for acetylcholine receptor function, encodes an unfamiliar protein Michael Hengartner, Nancy Tsung, Jim Lewist, and Bob Horvitz HHMI, Dept. Biology, MIT, Cambridge, MA 02139, USA. t Division of Life Sciences, U. of Texas at San Antonio, San Antonio, IX 78249

Holway AH et al. (2007) J Cell Biol "Checkpoint silencing during the DNA damage response in Caenorhabditis elegans embryos"

Kim SH, Michael WM, La Volpe A, Holway AH

[J Cell Biol, 2007]

After publication of this manuscript, the authors noticed that two images (Fig. 4 B, top left and middle) had been duplicated from a previous publication (Holway, A.H., C. Hung, and W.M. Michael. 2005. Genetics. 169:14511460). Here we provide new images corresponding to these control experiments. The authors apologize for this oversight.

Zhou MH et al. (1996) Worm Breeder's Gazette "Liquid Culture of the Worms with a Fermentor"

Zhou MH, Yang H, Walthall WW

[Worm Breeder's Gazette, 1996]

The yield of C. elegans and their food (E.coli) are relatively low in the large liquid cultures growth (Koelle et al.,1994) and the whole growth process is tedious. Here we report the successful growth of C.elegans with a fermentor. The following protocol is based on the protocol by Michael Koelle and Tory Herman (1994) from Internet.

Wu, Ziyun et al. (2017) International Worm Meeting "Longevity from dietary restriction and reduced insulin/IGF-1 signaling requires modulation of p38/ATF-7 innate immunity."

Blackwell, Keith, Steinbaugh, Michael, Wu, Ziyun, Isik, Meltem, Moroz, Natalie

[International Worm Meeting, 2017]

Dietary restriction (DR) and reduced insulin/IGF-1 signaling (rIIS) are the most robust environmental and genetic interventions, respectively, that to extend healthy lifespan in diverse organisms. In mammals, through unknown mechanisms DR reduces chronic inflammation, a cause of aging-related disease. Here we show that in C. elegans, DR and rIIS promote longevity by modulating innate immunity. For DR and rIIS lifespan extension, the conserved innate immunity pathway TIR-1(SARM)-NSY-1(ASK1)- SEK-1(MKK3)-PMK-1(p38)-ATF-7(ATF2) must be intact. However, in contrast to other protective mechanisms, p38/ATF-7 immune activity is reduced to a basal level by DR and rIIS, which mobilize other pathogen resistance programs. Elevated p38/ATF-7 immunity accelerates aging, but can be reversed by DR or rIIS to allow lifespan extension. We conclude that innate immunity modulation is critical for longevity assurance, and that regulation of immunity by anabolic signals may have contributed to immune system evolution.

Michael WM (2017) MicroPubl Biol "Asymmetric distribution of cyb-3 in 4-cell stage embryos."

Michael WM

[MicroPubl Biol, 2017]

Early embryos were fixed and stained with Mab F2F4 (green), shown to recognize CYB-3 (Michael, 2016), and DAPI, to illuminate the DNA (blue). Either wild type or par-4 mutant embryos were examined, after 24-hour incubation at 25C (the non-permissive temperature for the it47 allele of par-4). Anterior is to the left in all images. The data presented here reveals previously not shown data that depicts CYB-3 as asymmetrically distributed at the 4-cell stage. These data further support reported findings in Michael, 2016. There is more CYB-3 in the AB cell relative to its sister P1. In 4-cell embryos there is more CYB-3 in the EMS cell relative to its sister, P2. Thus, during P-lineage divisions, CYB-3 is asymmetrically distributed such that the somatic precursor receives more than its germline precursor sister cell. This asymmetry is abolished in par-4 mutant embryos, where all blastomeres contain equivalent amounts of CYB-3.

Vairoletti F et al. (2019) Medchemcomm "Synthesis of bicyclic 1,4-thiazepines as novel anti-Trypanosoma brucei brucei agents."

Medeiros A, Fontan P, Jancik V, Melendrez J, Saiz C, Vairoletti F, Tabarez C, Mahler G, Franco J, Salinas G, Comini MA, Saldana J

[Medchemcomm, 2019]

1,4-Thiazepines derivatives are pharmacologically important heterocycles with different applications in medicinal chemistry. In the present work, we describe the preparation of new bicyclic thiazolidinyl-1,4-thiazepines <b>3</b> by reaction between azadithiane compounds and Michael acceptors. The reaction scope was explored and the yields were optimized. The activity of the new compounds was evaluated against <i>Nippostrongylus brasiliensis</i> and <i>Caenorhabditis elegans</i> as anthelmintic models and <i>Trypanosoma brucei brucei.</i> The most active compound was <b>3l</b>, showing an EC₅₀ = 2.8 +/- 0.7 M against <i>T. b. brucei</i> and a selectivity index &gt;71.

Kron M et al. (2000) Parasitol Today "Lymphatic filariasis in the Philippines."

Kron M, Libranda-Ramirez B, Hernandez L, Torres E, Walker E

[Parasitol Today, 2000]

Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is endemic throughout most of the southern half of the Philippine archipelago. Economic and manpower shortages prior to 1996 made it difficult to acquire new prevalence data and vector control data concurrently from all provinces. Nevertheless, analysis of cumulative prevalence data on filariasis indicates the persistence of filariasis in each of the three major island groups - Luzon, Visayas and Mindanao - including 45 out of 77 provinces. Here, Michael Kron and colleagues summarize the prevalence data, and review host, parasite and vector characteristics relevant to the design and implementation of disease control initiatives in the Philippines planned for the year 2000.

Mango S (2009) Curr Biol "Q&A: Susan Mango."

Mango S

[Curr Biol, 2009]

Susan Mango is Benning Professor of Oncological Sciences at the University of Utah and an Investigator at the Huntsman Cancer Institute. She grew up in England and Washington D.C. before attending Harvard University. She received her Ph.D. from Princeton, where she studied the c-myc oncogene with Michael Cole. She was introduced to the nematode Caenorhabditis elegans as a postdoc with Judith Kimble at the University of Wisconsin - Madison, and moved to Utah in 1996 to start her own lab. After 13 years at the University of Utah, she will move to Harvard University in July 2009. Her principal focus is transcriptional strategies of organ development, using the C. elegans foregut as a model.