Goetinck SD et al. (1994) J Cell Biol "The Caenorhabditis elegans UNC-87 protein is essential for maintenance, but not assembly, of bodywall muscle."

Goetinck SD, Waterston RH

[J Cell Biol, 1994]

Mutations in the unc-87 gene of Caenorhabditis elegans cause disorganization of the myofilament lattice in adult bodywall muscle. In order to assess the organization of specific bodywall muscle components in the absence of the unc-87 gene product, we examined the bodywall muscles of mutant animals using phalloidin and monoclonal antibodies to various muscle proteins. These studies indicated that the bodywall muscle of unc-87 embryos is initially almost wild type in its organization, but at later stages, the muscle becomes severely disorganized. To address the possibility that this disorganization is due to deterioration of the muscle as a result of contraction, we introduced into the unc-87 mutant background a mutation that decreases myosin heavy chain activity but does not substantially affect muscle structure. The improved muscle structure and motility of the double mutants are consistent with the hypothesis that at least part of the disorganization phenotype of unc-87 mutants is a consequence of the wild-type levels of force generated during muscle contraction. These results imply that the role of the unc-87 gene product is not in specifying organization but rather in serving as a structural

Goetinck SD et al. (1994) J Cell Biol "The Caenorhabditis elegans muscle-affecting gene unc-87 encodes a novel thin filament-associated protein."

Waterston RH, Goetinck SD

[J Cell Biol, 1994]

Mutations in the unc-87 gene of Caenorhabditis elegans affect the structure and function of bodywall muscle, resulting in variable paralysis. We cloned the unc-87 gene by taking advantage of a transposon-induced allele of unc-87 and the correspondence of the genetic and physical maps in C. elegans. A genomic clone was isolated that alleviates the mutant phenotype when introduced into unc-87 mutants. Sequence analysis of a corresponding cDNA clone predicts a 357-amino acid, 40-kD protein that is similar to portions of the vertebrate smooth muscle proteins calponin and SM22alpha, the Drosophila muscle protein mp20, the deduced product of the C. elegans cDNA cm7g3, and the rat neuronal protein np25. Analysis of the genomic sequence and of various transcripts represented in a cDNA library suggest that unc-87 mRNAs are subject to alternative splicing. Immunohistochemistry of wildtype and mutant animals with antibodies to an unc-87 fusion protein indicates that the gene product is localized to the I-band of bodywall muscle. Studies of the UNC-87 protein in other muscle mutants suggest that the unc-87 gene product associates with thin filaments, in a manner that does not depend on the presence of the thin filament protein

Su C et al. (2020) Neurochem Int "Inhibitory Potency of 4- Substituted Sampangine Derivatives toward Cu2+ mediated aggregation of amyloid -peptide, Oxidative Stress, and Inflammation in Alzheimer's Disease."

Tang H, Chen K, Li W, Su C, Chen Y

[Neurochem Int, 2020]

Cu²⁺ plays a key role in the pathogenesis of Alzheimer's disease (AD). The dysregulation of Cu²⁺ can cause neuronal damage and aggravate development of AD. Moreover, a series of 4-substituted sampangine derivatives have been investigated as inhibitors of acetylcholinesterase and -amyloid (A) aggregation for the treatment of AD in our previous studies. In the present study, we reported that one of these derivatives SD-1 was able to modulate Cu²⁺-mediated multiple pathological elements in AD. The high selectivity of SD-1 for Cu²⁺ over other biologically relevant metal ions was demonstrated by ITC. Western blotting analysis, light-scattering study, DCF-DA assay and paralysis experiment indicated that SD-1 suppressed the formation of Cu²⁺-A species, alleviated the Cu²⁺-A species induced neurotoxicity and inhibited the production of ROS catalyzed by Cu²⁺-A species in SH-SY5Y cells over-expressing the Swedish mutant form of human APP (APPsw SH-SY5Y) and A42 transgenic C elegans (CL2020). Furthermore, SD-1 inhibited the expressions of NO, iNOS, TNF-, IL-1 and IL-6 induced by Cu²⁺ in BV2 microglial cells. Collectively, these findings provided valuable insights into the design and development of potent metal-chelating agents for AD treatment.

Fan PC et al. (1985) Southeast Asian J Trop Med Public Health "Experimental infection of subperiodic Brugia malayi in laboratory rats with emphasis on evaluation by four techniques."

Hsu YP, Huang CM, Wu CC, Ho CM, Fan PC

[Southeast Asian J Trop Med Public Health, 1985]

Infective larvae of subperiodic B. malayi from South Kalimantan (Borneo), Indonesia collected from laboratory-raised Ae. togoi mosquitoes after feeding on infected mongolian gerbils (Meriones unguiculatus) were inoculated subcutaneously into the groin areas of 15 SD and 36 LE rats. Blood was examined weekly by membrane filtration and thick smears starting 10 weeks post-infection. Microfilariae were found in 3 SD and 4 LE rats, the mf infection rate of 20% and 11% respectively. The prepatent period was significantly shorter in the SD rats (99-112 days) than those in the LE rats (110-153 days). The patent period was longer in the LE rats (208-703 days) than in the SD rats (236-543 days), and the mf density was similar (17.5 mf/20 c.mm blood against 16 mf/20 c.mm blood). At necropsy, 6 (3 female and 3 male) adult worms were recovered from 3 of 6 SD rats and 12 (9 female and 3 male) adult worms from 4 of 20 LE rats; all worms were found in the testes. The results of xenodiagnostic, histochemical staining and measuring spicules and protuberances, demonstrated clearly the difference between both species of Brugia. All dissected Ar. subalbatus mosquitoes exposed to B. pahangi became infected (100%), but none of those to subperiodic B. malayi were infected (0%). The mf of both species of Brugia in thick films stained with naphthol-AS-TR-phosphate showed that the excretory and anal pores of subperiodic B. malayi mf exhibited acid phosphatase activity and only a little activity was seen in other parts; while B. pahangi mf showed heavy diffuse acid phosphatase activity along the entire length of the body.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Wu Y et al. (2018) Mol Biol Cell "Single molecule dynamics of the P granule scaffold MEG-3 in the C. elegans zygote."

Griffin EE, Han B, Singh A, Gauvin TJ, Wu Y, Smith J

[Mol Biol Cell, 2018]

During the asymmetric division of the C. elegans zygote, germ (P) granules are disassembled in the anterior cytoplasm and stabilized/assembled in the posterior cytoplasm, leading to their inheritance by the germline daughter cell. P granule segregation depends on MEG-3 and MEG-4, which are enriched in P granules and in the posterior cytoplasm surrounding P granules. Here, we use single molecule imaging and tracking to characterize the reaction/diffusion mechanisms that underpin MEG-3::Halo segregation. We find that the anteriorly-enriched RNA-binding proteins MEX-5 and MEX-6 suppress the retention of MEG-3 in the anterior cytoplasm, leading to MEG-3 enrichment in the posterior. We provide evidence that MEX-5/6 may work in conjunction with PLK-1 kinase to suppress MEG-3 retention in the anterior. Surprisingly, we find that the retention of MEG-3::Halo in the posterior cytoplasm surrounding P granules does not contribute significantly to the maintenance of P granule asymmetry. Rather, our findings suggest that the formation of the MEG-3 concentration gradient and the segregation of P granules are two parallel manifestations of MEG-3's response to upstream polarity cues. Movie S1 Movie S1 near-TIRF imaging of PGL-1::GFP. Movie S2 Movie S2 near-TIRF imaging of MEG-3::Halo and PGL-1::GFP. Movie S3 Movie S3 near-TIRF imaging of Meg-3::meGFP. Movie S4 Movie S4 Spinning disk imaging of MEG-3::Halo and PGL-1::GFP. Movie S5 Movie S5 near-TIRF imaging of Meg-3::meGFP and PGL-1::GFP in an mbk-2(RNAi) embryo. Movie S6 Movie S6 near-TIRF imaging of Meg-3::meGFP and PGL-1::GFP in an mex-5/6(RNAi) embryo. Movie S7 Movie S7 near-TIRF imaging of Meg-3::meGFP and PGL-1::GFP in an mex-5(T186A);mex-6(RNAi) embryo. Movie S8 Movie S8 near-TIRF imaging of Meg-3::meGFP and PGL-1::GFP in an plk-1(RNAi) embryo. Movie S9 Movie S9 near-TIRF imaging of Meg-3::meGFP and PGL-1::GFP embryos. FD to PG transition. Movie S10 Movie S10 near-TIRF imaging of Meg-3::meGFP and PGL-1::GFP embryos. FD to PG to SD transition. Movie S11 Movie S11 near-TIRF imaging of Meg-3::meGFP and PGL-1::GFP embryos. SD to PG transition. Movie S12 Movie S12 near-TIRF imaging of Meg-3::meGFP and PGL-1::GFP embryos. SD to PG to SD transition.

Dolo H et al. (2019) PLoS Negl Trop Dis "Integrated seroprevalence-based assessment of Wuchereria bancrofti and Onchocerca volvulus in two lymphatic filariasis evaluation units of Mali with the SD Bioline Onchocerciasis/LF IgG4 Rapid Test."

Traore MO, Diallo AA, Dolo M, Diarra D, Dicko I, Zhang Y, Dolo H, Nutman TB, Coulibaly YI, Dembele B, Coulibaly SY, Coulibaly ME, Colebunders R, Dembele M, Soumaoro L, Doumbia SS, Goita S, Guindo B

[PLoS Negl Trop Dis, 2019]

BACKGROUND: Mali has become increasingly interested in the evaluation of transmission of both Wuchereria bancrofti and Onchocerca volvulus as prevalences of both infections move toward their respective elimination targets. The SD Bioline Onchocerciasis/LF IgG4 Rapid Test was used in 2 evaluation units (EU) to assess its performance as an integrated surveillance tool for elimination of lymphatic filariasis (LF) and onchocericiasis. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional survey with SD Bioline Onchocerciasis/LF IgG4 Rapid Test was piggy-backed onto a transmission assessment survey (TAS) (using the immunochromatographic card test (ICT) Binax Filariasis Now test for filarial adult circulating antigen (CFA) detection) for LF in Mali among 6-7 year old children in 2016 as part of the TAS in two EUs namely Kadiolo-Kolondieba in the region of Sikasso and Bafoulabe -Kita-Oussoubidiagna-Yelimane in the region of Kayes. In the EU of Kadiolo- Kolondieba, of the 1,625 children tested, the overall prevalence of W. bancrofti CFA was 0.62% (10/1,625) [CI = 0.31-1.09]; while that of IgG4 to Wb123 was 0.19% (3/1,600) [CI = 0.04-0.50]. The number of positives tested with the two tests were statistically comparable (p = 0.09). In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of W. bancrofti CFA was 0% (0/1,700) and that of Wb123 IgG4 antibody was 0.06% (1/1,700), with no statistically significant difference between the two rates (p = 0.99). In the EU of Kadiolo- Kolondieba, the prevalence of Ov16-specific IgG4 was 0.19% (3/1,600) [CI = 0.04-0.50]. All 3 positives were in the previously O. volvulus-hyperendemic district of Kolondieba. In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of Ov16-specific IgG4 was 0.18% (3/1,700) [CI = 0.04-0.47]. These 3 Ov16 IgG4 positives were from previously O.volvulus-mesoendemic district of Kita. CONCLUSIONS/SIGNIFICANCE: The SD Bioline Onchocerciasis/LF IgG4 Rapid test appears to be a good tool for integrated exposure measures of LF and onchocerciasis in co-endemic areas.

Maya A et al. (1997) Cell Biol Int "Necrosis of lung epithelial cells by filarial parasitic protein via an early induction of c-H-ras and TNF alpha expression."

Jayaraman K, Balakrishnan A, Maya A

[Cell Biol Int, 1997]

The direct interaction of filarial proteins with lung epithelial cells was examined to determine the possible mechanism of inducing cell death, an event that is observed in patients with tropical pulmonary eosinophilia. Exposure of lung epithelial cells to filarial parasitic proteins, Brugia malayi (BmA), Setaria digitata (Sd), and recombinant filarial protein (pGT 7) in vitro for more than 2 days, causes the appearance of DNA fragments both in the cytoplasm and culture supernatants, while no fragmentation was observed in the untreated controls. The release of DNA fragments both in the cytoplasm and the culture supernatants simultaneously, indicates that cell death is induced by a necrotic event rather than apoptosis. Fluorescent-labelled studies also indicate the fragmentation of DNA increasing in a time-dependent manner. Normal cellular function is controlled through several oncogenes. The modulation of specific proto-oncogenes like myc, ras and TNF alpha during exposure to filarial parasitic proteins reveal elevated levels of expression of ras and TNF alpha as early as 2 hours, implicating their involvement prior to DNA fragmentation leading to pathogenesis.

Lee H et al. (2019) Genetics "The Hippo Pathway Is Essential for Maintenance of Apicobasal Polarity in the Growing Intestine of Caenorhabditis elegans."

Kang J, Lee J, Ahn S, Lee H

[Genetics, 2019]

Although multiple determinants for establishing polarity in membranes of epithelial cells have been identified, the mechanism for maintaining the apicobasal polarity is not fully understood. Here, we show that the conserved Hippo kinase pathway plays a role in the maintenance of apicobasal polarity in the developing intestine of <i>Caenorhabditis elegans</i> We screened suppressors of the mutation in <i>wts-1</i>, the gene that encodes the LATS kinase homolog, the deficiency of which leads to disturbance of the apicobasal polarity of the intestinal cells and to eventual death of the organism. We identified several alleles of <i>yap-1</i> and <i>egl-44</i> that suppress the effects of this mutation. <i>yap-1</i> encodes a homolog of YAP/Yki, and <i>egl-44</i> encodes a homolog of TEAD/Sd. WTS-1 bound directly to YAP-1 and inhibited its nuclear accumulation in intestinal cells. We also found that NFM-1, which is a homolog of NF2/Merlin, functioned in the same genetic pathway as WTS-1 to regulate YAP-1 to maintain cellular polarity. Transcriptome analysis identified several target candidates of the YAP-1-EGL-44 complex including TAT-2, which encodes a putative P-type ATPase. In summary, we have delineated the conserved Hippo pathway in <i>C. elegans</i> consisting of NFM-1-WTS-1-YAP-1-EGL-44 and proved that the proper regulation of YAP-1 by upstream NFM-1 and WTS-1 is esssential for maintenance of apicobasal membrane identities of the growing intestine.

Attix, Haley et al. (2021) MicroPubl Biol

Cortez, Angel, Hastie, Eric, Attix, Haley, Zarilla, Kathy, Cho, Martin, George, Alex, Panchal, Henali

[MicroPubl Biol, 2021]

Research experiences in community college lead to increased retention in science, technology, engineering, and mathematics (STEM) (Nerio et al., 2019). This two week undergraduate research experience (URE) was designed to enhance laboratory skills in students with limited prior exposure, introduce developmental biology and genetics in a model organism system (C. elegans), and encourage participation in generation of data for a micropublication. The University of North Carolina at Chapel Hill and Durham Technical Community College partnered to host the URE for two weeks, for two hours, 4 days a week to limit lab time for students who work full time jobs. Here, we report our findings comparing early developmental cell division of wild type N2 embryos and a wild caught strain that was obtained from soil outside of Loeb Hall in Woods Hole, MA in 2017. The strain, originally called WH strain, was grown on OP50 and survived, suggesting it is a bacteriovore. The WH nematode lays embryos at the one cell stage, making early divisions observable without the dissection or bleaching required for the N2 strain. Students used primers to amplify the 18S ribosomal subunit geneused in phylogenetic analysis of taxafrom extracted genomic DNA and sent the product for sequencing (Floyd et al., 2005). The hairpin 17 region was selected to display a comparison because of high conservation (Nyaku et al., 2013). BLAST results for the N2 strain matched N2 and results for the wild caught WH strain matched with the nematode strain Acrobeloides sp. LKC 27 (a match of 99.7% and E value of 0), available from the Caenorhabditis Genetics Center. LKC 27 was isolated from a western corn rootworm from a Brookings, SD insectary in 2003 (personal communication with Dr. Lynn Carta, USDA-ARS). Students concluded that additional loci need to be examined to determine the relationship of the WH strain to LKC 27.