Hatanaka R et al. (2024) Genetics "The impact of differential transposition activities of autonomous and non-autonomous hAT transposable elements on genome architecture and gene expression in Caenorhabditis inopinata."

Tamagawa K, Haruta N, Sugimoto A, Hatanaka R

[Genetics, 2024]

Transposable elements (TEs) are DNA sequences capable of moving within genomes and significantly influence genomic evolution. The nematode Caenorhabditis inopinata exhibits a much higher TE copy number than its sister species, C. elegans. In this study, we identified a novel autonomous TE belonging to the hAT superfamily from a spontaneous TE-insertion mutant in C. inopinata and named this transposon Ci-hAT1. Further bioinformatic analyses uncovered three additional autonomous hAT elements-Ci-hAT2, Ci-hAT3, and Ci-hAT4-along with over 1,000 copies of two non-autonomous miniature inverted-repeat transposable elements (MITEs), mCi-hAT1 and mCi-hAT4, likely derived from Ci-hAT1 and Ci-hAT4 through internal deletion. We tracked at least three sequential transpositions of Ci-hAT1 over several years. However, the transposition rates of the other three autonomous hAT elements were lower, suggesting varying activity levels. Notably, the distribution patterns of the two MITE families differed significantly: mCi-hAT1 was primarily located in the chromosome arms, a pattern observed in the TEs of other Caenorhabditis species, whereas mCi-hAT4 was more evenly distributed across chromosomes. Additionally, interspecific transcriptome analysis indicated that C. inopinata genes with upstream or intronic these MITE insertions tend to be more highly expressed than their orthologous genes in C. elegans. These findings highlight the significant role of de-silenced TEs in driving the evolution of genomes and transcriptomes, leading to species-specific genetic diversity.

Holtzman EJ et al. (1998) Am J Physiol "Cloning, characterization, and gene organization of K-Cl cotransporter from pig and human kidney and C. elegans."

Dunham PB, Logue PJ, Kumar S, Holtzman EJ, Faaland CA, Waldman J, Ricken G, Erickson SJ, Warner F

[Am J Physiol, 1998]

We isolated and characterized the cDNAs far the human, pig, and Caenorhabditis elegans K-CI cotransporters. The pig and human homologs are 94% identical and contain 1,085 and 1,086 amino acids, respectively. The deduced protein of the C. elegans K-CI cotransporter clone (CE-KCC1) contains 1,003 amino acids. The mammalian K-CI cotransporters share similar to 45% similarity with CE-KCC1. Hydropathy analyses of the three clones indicate typical KCC topology patterns with 12 transmembrane segments, large extracellular loops between transmembrane domains 5 and 6 (unique to KCC), and large COOH-terminal domains. Human KCC1 is widely expressed among various tissues. This KCC1 gene spans 23 kb and is organized in 24 exons, whereas the CE-KCC1 gene spans 3.5 kb and contains ID exons. Transiently and stably transfected human embryonic kidney cells (HEK-293) expressing the human, pig, and C. elegans K-Cl cotransporter fulfilled two (pig) or five (human and C. elegans) criteria for increased expression of the K-Cl cotransporter. The criteria employed were basal K-CI cotransport; stimulation of cotransport by swelling, N-ethylmaleimide, staurosporine, and reduced cell Mg concentration; and secondary stimulation of Na-K-CI cotransport.

Iakoubov L et al. (2013) PLoS One "A common copy number variation (CNV) polymorphism in the CNTNAP4 gene: association with aging in females."

Puzianowska-Kuznicka M, Szwed M, Iakoubov L, Duan Z, Mossakowska M, Sesti F

[PLoS One, 2013]

BACKGROUND: Aging is a biological process strongly determined by genetics. However, only a few single nucleotide polymorphisms (SNPs) have been reported to be consistently associated with aging. While investigating whether copy number variations (CNVs) could fill this gap, we focused on CNVs that have not been studied in previous SNP-based searches via tagging SNPs. METHODS: TaqMan qPCR assays were developed to quantify 20 common CNVs in 222 senior American Caucasians in order to reveal possible association with longevity. The replication study was comprised of 1283 community-dwelling senior European Caucasians. Replicated CNVs were further investigated for association with healthy aging and aging-related diseases, while association with longevity was additionally tested in Caenorhabditis elegans. RESULTS: In the discovery study of 80 vs.<80 years old seniors, a homozygous intronic CNV deletion in the CNTNAP4 gene was inversely associated with survival to the age of 80 (OR=0.51, 95%CI 0.29-0.87, p=0.015 before correction for multiple testing). After stratification by sex, association remained significant in females (OR=0.41, 95%CI 0.21-0.77, p=0.007), but not in males (OR=0.97, 95%CI 0.33-2.79, p=1). The finding was validated in a replication study (OR=0.66, 95%CI 0.48-0.90, p=0.011 for females). CNTNAP4 association with longevity was supported by a marked 25% lifespan change in C. elegans after knocking down the ortholog gene. An inverse association of the CNV del/del variant with female healthy aging was observed (OR=0.39, 95%CI 0.19-0.76, p=0.006). A corresponding positive association with aging-related diseases was revealed for cognitive impairment (OR=2.17, 95%CI 1.11-4.22, p=0.024) and, in independent studies, for Alzheimer's (OR=4.07, 95%CI 1.17-14.14, p=0.036) and Parkinson's (OR=1.59, 95%CI 1.03-2.42, p=0.041) diseases. CONCLUSION: This is the first demonstration for association of the CNTNAP4 gene and one of its intronic CNV polymorphisms with aging. Association with particular aging-related diseases awaits replication and independent validation.

Lindblade KA et al. (2007) Am J Trop Med Hyg "Elimination of Onchocercia volvulus transmission in the Santa Rosa focus of Guatemala."

Richards FO, Unnasch TR, Catu E, Lindblade KA, Zea-Flores G, Castro J, Richards J, Punkosdy GA, Porter CH, Cruz-Ortiz N, Arana B, Dominguez A, Rizzo N, Oliva O, Sauerbrey M

[Am J Trop Med Hyg, 2007]

To eliminate transmission of Onchocerca volvulus, semiannual mass treatment with ivermectin (Mectizan; donated by Merck & Co) has been underway in Guatemala since 2000. We applied the 2001 World Health Organization (WHO) elimination criteria in the Santa Rosa focus of onchocerciasis transmission in Guatemala (10,923 persons at risk). No evidence of parasite DNA was found in 2,221 Simulium ochraceum vectors (one-sided 95% confidence interval [CI], 0-0.086%), and no IgG4 antibody positives to recombinant antigen OV16 were found in a sample of 3,232 school children (95% CI, 0-0.009%). We also found no evidence of microfilariae in the anterior segment of the eye in 363 area residents (95% CI, 0-0.08%). Our interpretation of these data, together with historical information, suggest that transmission of O. volvulus is permanently interrupted in Santa Rosa and that ivermectin treatments there can be halted.

Rodriguez-Perez MA et al. (2010) Am J Trop Med Hyg "Lack of active Onchocerca volvulus transmission in the northern Chiapas focus of Mexico."

Pena-Flores GP, Prado-Velasco G, Dominguez-Vazquez A, Morales-Castro AL, Rodriguez-Perez MA, Orozco-Algarra ME, Unnasch TR, Richards F

[Am J Trop Med Hyg, 2010]

The northern Chiapas onchocerciasis focus has undergone 11 years of ivermectin mass treatment. No evidence of microfilariae in the cornea and/or anterior chamber of the eye or in skin snips was seen in residents examined in 2006 in two sentinel communities (upper limit of the 95% confidence interval [UL 95% CI] = 0.5% and 0.3%, respectively). In children 10 and under, 0 of 305 were found to harbor antibodies to Ov16, a marker of parasite exposure; 0 of 4,400 Simulium ochraceum s.l. collected in 2005 contained parasite DNA, giving an UL 95% CI for the infective rate of 0.9/2,000, and an UL 95% CI of the seasonal transmission potential of 1.2 L3/person. These data, assumed to be representative of the focus as a whole, suggest that there is no ongoing transmission of Onchocerca volvulus in the northern Chiapas focus. Community-wide treatments with ivermectin were halted in 2008, and a post-treatment surveillance phase was initiated.

Zhang J et al. (2021) Cancers (Basel) "Worm-Based Microfluidic Biosensor for Real-Time Assessment of the Metastatic Status."

Chua SL, Khoo BL, Zhang J

[Cancers (Basel), 2021]

Metastasis is a complex process that affects patient treatment and survival. To routinely monitor cancer plasticity and guide treatment strategies, it is highly desired to provide information about metastatic status in real-time. Here, we proposed a worm-based (WB) microfluidic biosensor to rapidly monitor biochemical cues related to metastasis in a well-defined environment. Compared to conventional biomarker-based methods, the WB biosensor allowed high throughput screening under low cost, requiring only visual quantification of outputs; Methods: Caenorhabditis elegans were placed in the WB biosensor and exposed to samples conditioned with cancer cell clusters. The chemotactic preference of these worms was observed under discontinuous imaging to minimize the impact on physiological activity; Results: A chemotaxis index (CI) was defined to standardize the quantitative assessment from the WB biosensor, where moderate (3.24-6.5) and high (>6.5) CI levels reflected increased metastasis risk and presence of metastasis, respectively. We demonstrated that the secreted metabolite glutamate was a chemorepellent, and larger clusters associated with increased metastatic potential also enhanced CI levels; Conclusions: Overall, this study provided a proof of concept for the WB biosensors in assessing metastasis status, with the potential to evaluate patient-derived cancer clusters for routine management.

Grimes JE et al. (2016) PLoS Negl Trop Dis "School Water, Sanitation, and Hygiene, Soil-Transmitted Helminths, and Schistosomes: National Mapping in Ethiopia."

Mekete K, Wuletaw Y, French MD, Harrison WE, Gebretsadik A, Templeton MR, Gardiner IA, Yard E, Tadesse G, Grimes JE, Drake LJ

[PLoS Negl Trop Dis, 2016]

BACKGROUND: It is thought that improving water, sanitation, and hygiene (WASH) might reduce the transmission of schistosomes and soil-transmitted helminths, owing to their life cycles. However, few large-scale studies have yet assessed the real extent of associations between WASH and these parasites. METHODOLOGY/PRINCIPAL FINDINGS: In the 2013-2014 Ethiopian national mapping of infections with these parasites, school WASH was assessed alongside infection intensity in children, mostly between 10 and 15 years of age. Scores were constructed reflecting exposure to schistosomes arising from water collection for schools, from freshwater sources, and the adequacy of school sanitation and hygiene facilities. Kendall's b was used to test the WASH scores against the school-level arithmetic mean intensity of infection with each parasite, in schools with at least one child positive for the parasite in question. WASH and parasitology data were available for 1,645 schools. More frequent collection of water for schools, from open freshwater sources was associated with statistically significantly higher Schistosoma mansoni infection intensity (Kendall's b = 0.097, 95% confidence interval, CI: 0.011 to 0.18), better sanitation was associated with significantly lower Ascaris lumbricoides intensity (Kendall's b = -0.067, 95% CI: -0.11 to -0.023) and borderline significant lower hookworm intensity (Kendall's b = -0.039, 95% CI: -0.090 to 0.012, P = 0.067), and better hygiene was associated with significantly lower hookworm intensity (Kendall's b = -0.076, 95% CI: -0.13 to -0.020). However, no significant differences were observed when comparing sanitation and infection with S. mansoni or Trichuris trichiura, or hygiene and infection with A. lumbricoides or T. trichiura. CONCLUSIONS/SIGNIFICANCE: Improving school WASH may reduce transmission of these parasites. However, different forms of WASH appear to have different effects on infection with the various parasites, with our analysis finding the strongest associations between water and S. mansoni, sanitation and A. lumbricoides, and hygiene and hookworm.

Lewis JA et al. (1984) Journal of Labelled Compounds & Radiopharmaceuticals "Preparation of tritium-labelled meta-aminolevamisole of high specific radioactivity by catalytic dehalogenation."

Lewis JA, Paterson I

[Journal of Labelled Compounds & Radiopharmaceuticals, 1984]

We describe the synthesis of tritiated meta-aminolevamisole (MAL) of high specific radioactivity. Unlabelled MAL was iodinated with iodine monochloride in aqueous hydrochloric acid. The major reaction product, L[-]2,3,5,6-tetrahydro-6-(5-amino-2-iodophenyl)imidazo [2,1-b]thiazole, was catalytically dehalogenated with carrier-free tritium gas in methanolic potassium hydroxide over 10% palladium-carbon. After extraction and chromatography, a radioactive species ([3H]-MAL) was identified with the same chromatographic motility as unlabelled MAL. [3H]-MAL possesses the same high biological activity in contracting nematode muscle as authentic unlabelled MAL, co-chromatographs with unlabelled MAL in three different TLC systems and is about 90% radiochemically pure. By bioassay and competitive inhibition studies, the specific radioactivity of [3H]-MAL appears greateer than 15 Ci/mmole and is probably close to 29 Ci/mmole. [3H]-MAL was shown to be useful for detecting a high affinity, saturable binding activity in extracts of the nematode Caenorhabditis elegans.

Ali MM et al. (2007) Am J Trop Med Hyg "Fc gamma RIIa (CD32) polymorphism and onchocercal skin disease: implications for the development of severe reactive onchodermatitis (ROD)."

Berzins K, Montgomery SM, Farouk SE, Shamad MM, Noori SI, Fadlelseed OE, Nasr A, Ali MM, Elghazali G

[Am J Trop Med Hyg, 2007]

The pathologic manifestations of Onchocerca volvulus infection depend on the interplay between the host and the parasite. A genetic single nucleotide polymorphism in the Fc gamma RIIa gene, resulting in arginine (R) or histidine (H) at position 131, affects the binding to the different IgG subclasses and may influence the clinical variations seen in onchocerciasis. This study investigated the relationship between this polymorphism and disease outcome. Fc gamma RIIa genotyping was performed on clinically characterized onchocerciasis patients (N = 100) and healthy controls (N = 74). Fc gamma RIIa genotype R/R131 frequencies were significantly higher among patients with severe dermatopathology (P < 0.001). Increased risk of developing this form was mostly associated with one tribe (Masalit) (OR = 3.2, 95% CI 1-9.9, P = 0.042). The H131 allele was found to be significantly associated with a reduced risk of having the severe form of the disease (adjusted OR = 0.26, 95% CI = 0.13-0.46, P < 0.001). Our findings suggest that the polymorphism influences the clinical outcome of onchocerciasis.

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.