Sugawara T et al. (2018) Br J Nutr "Killed Bifidobacterium longum enhanced stress tolerance and prolonged life span of Caenorhabditis elegans via DAF-16."

Sakamoto K, Sugawara T

[Br J Nutr, 2018]

Probiotics are bacteria among the intestinal flora that are beneficial for human health. Bifidobacterium longum (BL) is a prototypical probiotic that is widely used in yogurt making, supplements and others. Although various physiological effects of BL have been reported, those associated with longevity and anti-ageing still remain elusive. Here we aimed to elucidate the physiological effects of killed BL (BR-108) on stress tolerance and longevity of Caenorhabditis elegans and their mechanisms. Worms fed killed BL in addition to Escherichia coli (OP50) displayed reduced body length in a BL dose-dependent manner. When compared with those fed E. coli alone, these worms had a higher survival rate following heat stress at 35C and hydrogen peroxide-induced oxidative stress. A general decrease in motility was observed over time in all worms; however, killed BL-fed ageing worms displayed increased movement and longer life span than those fed E. coli alone. However, the longevity effect was suppressed in sir-2.1, daf-16 and skn-1-deficient worms. Killed BL induced DAF-16 nuclear localisation and increased the expression of the DAF-16 target gene hsp-12.6. These results revealed that the physiological effects of killed BL in C. elegans were mediated by DAF-16 activation. These findings contradict previous observations with different Bifidobacterium and Lactobacillus strains, which showed the role for SKN-1 independently of DAF-16.

Mintzer EA et al. (2002) FEBS Lett "Behavior of a photoactivatable analog of cholesterol, 6-photocholesterol, in model membranes."

Mintzer EA, Wilschut J, Waarts BL, Bittman R

[FEBS Lett, 2002]

6-Photocholesterol, a new photoactivatable analog of cholesterol in which a diazirine functionality replaces the 5,6-double bond in the steroid nucleus, was used recently to identify cholesterol-binding proteins in neuroendocrine cells [Thiele, C., Hannah, M.J., Farenholz, F. and Huttner, W.B. (2000) Nat. Cell Biol. 2, 42-49], to track the distribution and transport of cholesterol in Caenorhabditis elegans [Matyash, V., Geier, C., Henske, A., Mukherjee, S., Hirsh, D., Thiele, C., Grant, B., Maxfield, F.R. and Kurzchalia, T.V. (2001) Mol. Biol. Cell 12, 1725-1736], and to probe lipid-protein interactions in oligodendrocytes [Simons, M., Kramer, E.M., Thiele, C., Stoffel, W. and Trotter, J. (2000) J. Cell Biol. 151, 143-154]. To determine whether 6-photocholesterol is a faithful mimetic of cholesterol we analyzed the ability of this probe, under conditions in which it is not photoactivated to a carbene, to substitute for cholesterol in two unrelated assays: (1) to condense 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine monomolecular films and (2) to mediate the fusion of two alphaviruses (Semliki Forest and Sindbis) with liposomes. The results suggest that this analog is a suitable photoprobe of cholesterol.

Park JE et al. (2022) Adv Sci (Weinh) "Multi-Modal Locomotion of Caenorhabditis elegans by Magnetic Reconfiguration of 3D Microtopography."

Park JE, Jhang S, Lee SG, Kim CR, Kim SM, Jeon TJ, Jeon J, Wie JJ, Yoon S

[Adv Sci (Weinh), 2022]

Miniaturized untethered soft robots are recently exploited to imitate multi-modal curvilinear locomotion of living creatures that perceive change of surrounding environments. Herein, the use of Caenorhabditis elegans (C. elegans) is proposed as a microscale model capable of curvilinear locomotion with mechanosensing, controlled by magnetically reconfigured 3D microtopography. Static entropic microbarriers prevent C. elegans from randomly swimming with the omega turns and provide linear translational locomotion with velocity of ≈0.14 BL s-1 . This velocity varies from ≈0.09 (for circumventing movement) to ≈0.46 (for climbing) BL s-1 , depending on magnetic bending and twisting actuation coupled with assembly of microbarriers. Furthermore, different types of neuronal mutants prevent C. elegans from implementing certain locomotion modes, indicating the potential for investigating the correlation between neurons and mechanosensing functions. This strategy promotes a platform for the contactless manipulation of miniaturized biobots and initiates interdisciplinary research for investigating sensory neurons and human diseases.

Yu Z et al. (2011) J Environ Sci (China) "Behavior toxicity to Caenorhabditis elegans transferred to the progeny after exposure to sulfamethoxazole at environmentally relevant concentrations."

Yu Z, Jiang L, Yin D

[J Environ Sci (China), 2011]

Sulfamethoxazole (SMX) is one of the most common detected antibiotics in the environment. In order to study whether SMX can affect behavior and growth and whether these effects could be transferred to the progeny, Caenorhabditis elegans was exposed at environmentally relevant concentrations for 24, 48, 72 and 96 hr, respectively. After exposure, the exposed parent generation (P0) was measured for behavior and growth indicators, which were presented as percentage of controls (POC). Then their corresponding unexposed progeny (F1) was separated and measured for the same indicators. The lowest POC for P0 after 96 hr-exposure at 100 mg/L were 37.8%, 12.7%, 45.8% and 70.1% for body bending frequency (BBF), reversal movement (RM), Omega turns (OT) and body length (BL), respectively. And F1 suffered defects with the lowest POC as 55.8%, 24.1%, 48.5% and 60.7% for BBF, RM, OT and BL, respectively. Defects in both P0 and F1 showed a time- and concentration-dependent fashion and behavior indicators showed better sensitivity than growth indicator. The observed effects on F1 demonstrated the transferable properties of SMX. Defects of SMX at environmental concentrations suggested that it is necessary to perform further systematical studies on its ecological risk in actual conditions.

Yu Z et al. (2013) J Hazard Mater "Inhibitions on the behavior and growth of the nematode progeny after prenatal exposure to sulfonamides at micromolar concentrations."

Zhang J, Deng H, Yin D, Chen X, Yu Z

[J Hazard Mater, 2013]

Sulfonamides are one typical antibiotic which is an emerging hazardous material to the ecological stability due to their continuously application and biological effects to non-target organisms. The parent-progeny transgenerational effects need investigations to indicate their long-term consequences. Currently, we tested the transgenerational effects of sulfadiazine (SD), sulfapyridine (SP) and sulfamethazine (SMZ) on L3 larva of Caenorhabditis elegans. The nematodes were exposed to aqueous sulfonamides at micromolar concentrations for 96 h, and then the effects on the behavior and growth in the exposed parent and unexposed progeny were measured. Results showed that SD, SP and SMZ inhibited three behavior indicators including body bending frequency (BBF), reversal movement (RM) and Omega turn (OT), and the growth indicator (body length, BL). Behavior indicators showed higher sensitivities than the growth indicator, and BBF had the highest sensitivity among the behavior indicators. Moreover, the effects of sulfonamides were also observed in the unexposed progeny with partially rescued or more severe inhibitions on the indicators. The behavior also showed higher sensitivity than the growth in the progeny. The transgenerational effects of sulfonamides indicated that parental exposure can multiply the harmful effects of antibiotic pollution in following generations and their potential ecological risks at environmental concentrations were further raised.

Perez-Escudero A et al. (2007) Proc Natl Acad Sci U S A "Optimally wired subnetwork determines neuroanatomy of Caenorhabditis elegans."

de Polavieja GG, Perez-Escudero A

[Proc Natl Acad Sci U S A, 2007]

Wiring cost minimization has successfully explained many structures of nervous systems. However, in the nematode Caenorhabditis elegans, for which anatomical data are most detailed, wiring economy is thought to play only a partial role and alone has failed to account for the grouping of neurons into ganglia [Chen BL, Hall DH, Chklovskii DB (2006) Proc Natl Acad Sci USA 103:4723-4728; Kaiser M, Hilgetag CC (2006) PLoS Comput Biol 2:e95; Ahn Y-Y, Jeong H, Kim BJ (2006) Physica A 367:531-537]. Here, we test the hypothesis that optimally wired subnetworks can exist within nonoptimal networks, thus allowing wiring economy to give an improved prediction of spatial structure. We show in C. elegans that the small subnetwork of wires connecting sensory and motor neurons with sensors and muscles, comprising only 15% of connections, is close to optimal and alone predicts the main features of the spatial segregation of neurons into ganglia and encephalization. Moreover, a method to dissect networks into optimal and nonoptimal components is shown to find a large near-optimal subnetwork of 84% of neurons with a very low position error of 5.4%, and that explains clustering of neurons into ganglia and encephalization to fine detail. In general, we expect realistic networks not to be globally optimal in wire cost. We thus propose the strategy of using near-optimal subnetworks to understand neuroanatomical structure.

Rajabli N et al. (2018) Int J Biochem Mol Biol "The dangers of sublethal carvacrol exposure: increases in virulence of Bacillus cereus during endophthalmitis."

Bange JS, McKillip JL, Kelly-Worden M, Ho Y, Nimmer PS, Williamson L, Rajabli N

[Int J Biochem Mol Biol, 2018]

<i>Bacillus cereus</i> can cause endophthalmitis through secretion of virulence factors, including hemolysin BL (Hbl) and nonhemolytic entertoxin (Nhe). Carvacrol is an extract from oregano oil, with potential for curtailing <i>B. cereus</i> endophthalmitis, due to antimicrobial and anti-inflammatory qualities. However, sublethal levels of carvacrol increases <i>B. cereus</i> virulence. The goal of this study was to investigate the increase in <i>B. cereus</i> virulence potential in response stress induced by a subinhibitory concentration (SIC) of carvacrol. Enterotoxin production and tissue damage were examined during ocular infections <i>in vitro</i> and <i>in vivo</i>. We hypothesized that the SIC of carvacrol would significantly increase toxin production in <i>B. cereus</i> without progressing systemically. RT-PCR determined SIC carvacrol-treated <i>B. cereus</i> had significantly higher <i>hblC</i> and <i>nheA</i> mRNA expression levels than controls <i>in vitro</i>. ELISA and RPLA analysis revealed a 46.8% and 50% increase in NheA and HblC toxin levels, respectively, in SIC-treated cultures. <i>Caenorhabditis elegans</i>-fed SIC carvacrol-treated <i>B. cereus</i> had a significantly higher mean mortality rate than nematodes fed untreated <i>B. cereus</i>. Significantly higher TNF- levels were observed in SIC carvacrol-treated <i>B. cereus</i> mice compared to other treatment groups except for mice infected with <i>B. cereus</i> alone. Significantly higher IL-6 levels were also found in SIC-<i>B. cereus</i> mice. Histological analysis using Rose-Bengal and DAPI determined that the eyes of mice infected with SIC carvacrol-treated <i>B. cereus</i> had significantly more damage than eyes treated with <i>B. cereus</i> alone. The SIC of carvacrol increased <i>B. cereus</i> virulence <i>in vitro</i> and <i>in vivo</i>, with a mild systemic infection noted.

Yu X et al. (2024) Front Aging Neurosci "P-hydroxybenzaldehyde protects Caenorhabditis elegans from oxidative stress and β-amyloid toxicity."

Tao J, Xiao T, Duan X, Yu X

[Front Aging Neurosci, 2024]

Introduction: Gastrodia elata is the dried tuber of the orchid Gastrodia elata Bl. It is considered a food consisting of a source of precious medicinal herbs, whose chemical composition is relatively rich. Gastrodia elata and its extracted fractions have been shown to have neuroprotective effects. P-hydroxybenzaldehyde (p-HBA), as one of the main active components of Gastrodia elata, has anti-inflammatory, antioxidative stress, and cerebral protective effects, which has potential for the treatment of Alzheimer's disease (AD). The aim of this study was to verify the role of p-HBA in AD treatment and to investigate its mechanism of action in depth based using the Caenorhabditis elegans (C. elegans) model.Methods: In this study, we used paralysis, lifespan, behavioral and antistress experiments to investigate the effects of p-HBA on AD and aging. Furthermore, we performed reactive oxygen species (ROS) assay, thioflavin S staining, RNA-seq analysis, qPCR validation, PCR Array, and GFP reporter gene worm experiment to determine the anti-AD effects of p-HBA, as well as in-depth studies on its mechanisms.Results: p-HBA was able to delay paralysis, improve mobility and resistance to stress, and delay aging in the AD nematode model. Further mechanistic studies showed that ROS and lipofuscin levels, A&#946; aggregation, and toxicity were reduced after p-HBA treatment, suggesting that p-HBA ameliorated A&#946;-induced toxicity by enhancing antioxidant and anti-aging activity and inhibiting A&#946; aggregation. p-HBA had a therapeutic effect on AD by improving stress resistance, as indicated by the down-regulation of NLP-29 and UCR-11 expression and up-regulation of PQN-75 and LYS-3 expression. In addition, the gene microarray showed that p-HBA treatment played a positive role in genes related to AD, anti-aging, ribosomal protein pathway, and glucose metabolism, which were collectively involved in the anti-AD mechanism of p-HBA. Finally, we also found that p-HBA promoted nuclear localization of DAF-16 and increased the expression of SKN-1, SOD-3, and GST-4, which contributed significantly to inhibition of A&#946; toxicity and enhancement of antioxidative stress.Conclusion: Our work suggests that p-HBA has some antioxidant and anti-aging activities. It may be a viable candidate for the treatment and prevention of Alzheimer's disease.