Nelson GA et al. "Nematode radiobiology and development in space. Results from IML-1."

Richards DG, Kazarians GA, Nelson GA, Benton EV, Henke R, Benton ER, Schubert WW

The International Microgravity Laboratory #1 Spacelab mission was launched on 22-Jan-1992 for an 8-day mission. The Radiat experiment was one of 17 investigations which used the ESA Biorack on IML-1 and it had two objectives. The first objective was to isolate and characterize mutations induced by cosmic rays; the second was to assess the fidelity of development in 0-gravity over two consecutive generations. Two strategies were used to isolate mutations in a set of essential genes or a specific gene and to correlate the genetic events with the passage of charged particles. The results were isolation of 60 lethal mutations whose phenotypes are related to the local pattern of energy deposition. 12 mutations in the unc-22 gene include large deletions as characterized by DNA hybridization studies. Development of nematodes proceeded through two consecutive generations with no obvious defects. Cytoplasmic determinants in embryos, nuclear location and symmetry of cellular anatomy were normal as were Mendelian segregation and recombination of

Nelson GA et al. (1993) International C. elegans Meeting "Radiobiology and development in space. Results from IML-1."

Richards DG, Nelson GA, Schubert WW, Kazarians GA

[International C. elegans Meeting, 1993]

Nelson GA et al. (1994) Adv Space Res "Radiation effects in nematodes: results from IML-1 experiments."

Benton ER, Benton EV, Henke R, Schubert WW, Richards GF, Nelson GA, Kazarians GA

[Adv Space Res, 1994]

The nematode Caenorhabditis elegans was exposed to natural space radiation using the ESA Biorack facility aboard Spacelab on International Microgravity Laboratory 1, STS-42. For the major experimental objective dormant animals were suspended in buffer or on agar or immobilized next to CR-39 plastic nuclear track detectors to correlate fluence of HZE particles with genetic events. This configuration was used to isolate mutations in a set of 350 essential genes as well as in the unc-22 structural gene. From flight samples 13 mutants in the unc-22 gene were isolated along with 53 lethal mutations from autosomal regions balanced by a translocation eT1(III;V). Preliminary analysis suggests that mutants from worms correlated with specific cosmic ray tracks may have a higher proportion of rearrangements than those isolated from tube cultures on a randomly sampled basis. Right sample mutation rate was approximately 8-fold higher than ground controls which exhibited laboratory spontaneous frequencies.

Muthinja JM et al. (2018) Cell Microbiol "Tailored environments to study motile cells and pathogens."

Spatz JP, Kruger T, Imle A, Muthinja JM, Ripp J, Engstler M, Fackler OT, Frischknecht F, Haraszti T

[Cell Microbiol, 2018]

Motile cells and pathogens migrate in complex environments and yet are mostly studied on simple 2D substrates. In order to mimic the diverse environments of motile cells a set of assays including substrates of defined elasticity, microfluidics, micropatterns, organotypic cultures and 3D gels have been developed. We briefly introduce these and then focus on the use of micro-patterned pillar arrays, which help to bridge the gap between 2D and 3D. These structures are made from polydimethylsiloxane, a moldable plastic and their use has revealed new insights into mechanoperception in Caenorhabditis elegans, gliding motility of Plasmodium, swimming of trypanosomes and nuclear stability in cancer cells. These studies contributed to our understanding of how the environment influences the respective cell and inform on how the cells adapt to their natural surroundings on a cellular and molecular level.

Nelson GA et al. (1997) International C. elegans Meeting "Radiation Effects in Space: Results from the STS-76 Space Shuttle Mission"

Wilde H, Schubert WW, Hlavacek A, Hartman PS, Kazarians GA, Benton E, Kern R, Nelson GA, Lewicki D, Schranck D

[International C. elegans Meeting, 1997]

The STS-76 (Shuttle-Mir 3) spaceflight provided an opportunity to test two questions about radiation responses in C. elegans. First, does the absence of gravity modify the dose-response relation for mutation and second, what are the features of the mutation spectrum resulting from exposure to cosmic rays? These questions were put to the test in space using the miniaturized biology laboratory "Biorack" which was housed in the Spacehab module aboard shuttle Atlantis. The mission flew in March, 1996 and was a shuttle rendezvous with the Russian space station Mir. To answer question 1 worms of balancer strain JP10 (dpy-18/3T1(III)III; unc-46/eT1(V) V)were launched as dauers in S medium. On orbit they were injected into a series of lexan tubes containing a cylindrical shell of agarose-gelled S medium with a central airspace. The agarose media also contained 0 to 1.3 mCi of 45CaCl2 (a Beta particle emitter) such that a dose vs response curve would be generated from each series of tubes. One series of tubes was incubated at 22 deg C at 0 gravity while a matched set was placed on a 1 x g centrifuge. Matched ground controls at 1 x g and 1.4 x g were also performed. Worms were washed and plated onto E. coli-seeded plates immediately after landing to recover the dauers and processed for autosomal recessive lethal mutation. The results showed that viability and fertility of worms were not significantly altered by gravity and that the mutation dose-response from 0 to 100 Gy yielding 0 to 7% mutants was also unmodulated. To answer question 2, fem-3(q20gf) dauer larvae (suspended in S buffer) were placed in lexan tubes and transferred on orbit from a storage locker to the Biorack where they were incubated for the duration of the mission at 22C. The cosmic ray environment for these worms was measured using a combination of thermoluminescent detectors and plastic nuclear track detectors included in the tube-holding container. Upon landing these animals were recovered and screened for mutants by a temperature shift to 25C. Twenty-six independent mutants were recovered, giving a mutation frequency of 2x10-5. This is approximately three times that for ground controls. Each strain was analyzed by Southern hybridization. Only one polymorphism was detected. This spectrum will be compared to those obtained using several ground-based radiation sources and to those obtained on a previous spaceflight (STS-42, IML-1).

Quartey MO et al. (2021) Sci Rep "The A(1-38) peptide is a negative regulator of the A(1-42) peptide implicated in Alzheimer disease progression."

Pennington PR, Heistad RM, Nyarko JNK, Barnes JR, Bolanos MAC, Parsons MP, Knudsen KJ, De Carvalho CE, Leary SC, Mousseau DD, Buttigieg J, Maley JM, Quartey MO

[Sci Rep, 2021]

The pool of -Amyloid (A) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for A peptides. We examined how a naturally occurring variant, e.g. A(1-38), interacts with the AD-related variant, A(1-42), and the predominant physiological variant, A(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that A(1-38) interacts differently with A(1-40) and A(1-42) and, in general, A(1-38) interferes with the conversion of A(1-42) to a -sheet-rich aggregate. Functionally, A(1-38) reverses the negative impact of A(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an A(1-42) phenotype in Caenorhabditis elegans. A(1-38) also reverses any loss of MTT conversion induced by A(1-40) and A(1-42) in HT-22 hippocampal neurons and APOE 4-positive human fibroblasts, although the combination of A(1-38) and A(1-42) inhibits MTT conversion in APOE 4-negative fibroblasts. A greater ratio of soluble A(1-42)/A(1-38) [and A(1-42)/A(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that A(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant A(1-42).

Danielle Thierry-Mieg et al. (2003) Worm Breeder's Gazette "www.wormgenes.org , a new gene centered database"

Vahan Simonyan, Michel Potdevin, Mark Sienkiewicz, Yuji KOHARA, Jean Thierry-Mieg, Danielle Thierry-Mieg, Tadasu SHIN-I

[Worm Breeder's Gazette, 2003]

Wormgenes is a new resource for C.elegans offering a detailed summary about each gene and a powerful query system.

Tangrodchanapong T et al. (2020) Front Pharmacol "Frondoside A Attenuates Amyloid- Proteotoxicity in Transgenic Caenorhabditis elegans by Suppressing Its Formation."

Tangrodchanapong T, Sobhon P, Meemon K

[Front Pharmacol, 2020]

Oligomeric assembly of Amyloid- (A) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A oligomers could halt the disease progression. In this study, by using transgenic <i>Caenorhabditis elegans</i> model of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumber <i>Cucumaria frondosa</i> saponin with anti-cancer activity, on A aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 M significantly delayed the worm paralysis caused by A aggregation as compared with control group. In addition, the number of A plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A species in the transgenic <i>C. elegans</i> were significantly reduced upon treatment with frondoside A, whereas the level of A monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A. Taken together, these data suggested that low dose of frondoside A could protect against A-induced toxicity by primarily suppressing the formation of A oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A aggregation should be studied and elucidated in the future.

Hodgkin JA (1998) International Journal of Developmental Biology "Seven types of pleiotropy."

Hodgkin JA

[International Journal of Developmental Biology, 1998]

Pleiotropy , a situation in which a single gene influences multiple phenotypic tra its, can arise in a variety of ways. This paper discusses possible underlying mechanisms and proposes a classification of the various phenomena involved.

Tuck S (2011) Curr Biol "Extracellular vesicles: budding regulated by a phosphatidylethanolamine translocase."

Tuck S

[Curr Biol, 2011]

Recent work on a Caenorhabditis elegans transmembrane ATPase reveals a central role for the aminophospholipid phosphatidylethanolamine in the production of a class of extracellular vesicles.