Verma SK et al. (2015) Vaccine "Protection against filarial infection by 45-49 kDa molecules of Brugia malayi via IFN--mediated iNOS induction."

Verma R, Verma SK, Kar S, Thota JR, Parmar N, Kushwaha V, Joseph SK, Yadav PK, Murthy PK

[Vaccine, 2015]

Nitric oxide (NO) mediated mechanisms have been implicated in killing of some life-stages of Brugia malayi/Wuchereria bancrofti and protect the host through type 1 responses and IFN- stimulated toxic mediators' release. However, the identity of NO stimulating molecules of the parasites is not known. Three predominantly NO-stimulating SDS-PAGE resolved fractions F8 (45.24-48.64 kDa), F11 (33.44-38.44 kDa) and F12 (28.44-33.44 kDa) from B. malayi were identified and their proteins were analyzed by 2-DE and MALDI-TOF/TOF. Tropomyosin, calponin and de novo peptides were identified by 2-DE and MALDI-TOF/TOF in F8 and immunization with F8 conferred most significant protection against L3-initiated infection in Mastomys coucha. Immunized animals showed upregulated F8-induced NO, IFN-, TNF-, IL-1, IL-10, TGF- release, cellular proliferative responses and specific IgG and IgG1. Anti-IFN-, anti-TNF-, and anti-IL-1 significantly reduced F8-mediated NO generation and iNOS induction at protein levels. Anti-IFN- treated cells showed maximum reduction (>74%) in NO generation suggesting a predominant role of IFN- in iNOS induction. In conclusion, the findings suggest that F8 which contains tropomyosin, calponin and de novo peptides protects the host via IFN- mediated iNOS induction and may hold promise as vaccine candidate(s). This is also the first report of identification of tropomyosin and calponin in B. malayi.

Verma R et al. (2018) Parasitol Res "Leishmania donovani molecules recognized by sera of filaria infected host facilitate filarial infection."

Thota JR, Kushwaha V, Murthy PK, Tewari P, Shukla PK, Vishwakarma P, Yadav PK, Kar S, Pandey S, Parmar N, Verma R

[Parasitol Res, 2018]

We earlier found that F6 fraction of human filaria Brugia malayi cross-reacted with sera of Leishmania donovani infected hamsters and immunization with F6 inhibited both filarial and leishmanial infections. In the present study, we identified a 52.9-93.6 kDa fraction (Ld1) of L. donovani that cross-reacted with sera of B. malayi infected animals and investigated effect of Ld1 on filarial infection. Immunization of BALB/c mice with Ld1 facilitated B. malayi infection with remarkable increase in parasite burden. Facilitation of filarial infection was associated with downregulated cell proliferation, IL-5, IL-13, IFN-, TNF-, and IL-2 levels and upregulated IL-4 and TGF-. Ld1 exposure also suppressed MHC class-I, MHC class-II, and FcR1 expression, and phagocytosis in naive mouse macrophages, and CD4+, CD8+, and CD19+ cell population in mouse spleen. Two-dimensional electrophoresis and matrix-assisted laser desorption ionization-time of flight-mass spectrometry revealed eight proteins in Ld1: putative heat shock protein (HSP) 70-related protein 1, HSP70 mitochondrial precursor, alanine aminotransferase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, protein disulfide isomerase, putative ATPase beta subunit, trypanothione reductase, and a hypothetical protein. HSP70 protein mitochondrial precursor and trypanothione reductase showed homology with Trypanosoma cruzi and L. donovani, respectively, and the rest 6 proteins including hypothetical protein bear homology with L. infantum. In conclusion, the present study for the first time shows that immunization with filarial cross-reactive Ld1 fraction of L. donovani facilitates filarial infection by modulating Th1 and Th2 responses. Ld1 molecules may therefore facilitate filarial infection in filaria-leishmania co-infection.

Bradford BR et al. (2020) Genetics "Counteracting Environmental Chemicals with Coenzyme Q10: An Educational Primer for Use with "Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline"."

Nowakowski AM, Maurina S, Checchi PM, FitzGibbon TC, Gervasio ED, Kelly M, Bradford BR, Fassnacht N, Benjamin AV, Briand NE

[Genetics, 2020]

Environmental toxicants are chemicals that negatively affect human health. Although there are numerous ways to limit exposure, the ubiquitous nature of certain environmental toxicants makes it impossible to avoid them entirely. Consequently, scientists are continuously working toward developing strategies for combating their harmful effects. Using the nematode <i>Caenorhabditis elegans</i>, a model with many genetic and physiological similarities to humans, researchers in the Colaiacovo laboratory have identified several molecular mechanisms by which the toxic agent bisphenol A (BPA) interferes with reproduction. Here, we address their recent discovery that a widely available compound, Coenzyme Q10 (CoQ10), can rescue BPA-induced damage. This work is significant in that it poses a low-cost method for improving reproductive success in humans. The goal of this primer is to assist educators and students with navigating the paper entitled &quot;Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the <i>Caenorhabditis elegans</i> Germline.&quot; It is ideally suited for integration into an upper-level undergraduate course such as Genetics, Cell and Molecular Biology, Developmental Biology, or Toxicology. The primer provides background information on the history of BPA, the utility of the <i>C. elegans</i> germ line as a model for studying reproductive toxicity, and research methods including assessment of programmed cell death, fluorescent microscopy applications, and assays to quantify gene expression. Questions for deeper exploration in-class or online are provided.<b>Related article in <i>GENETICS</i>:</b> Hornos Carneiro MF, Shin N, Karthikraj R, Barbosa F Jr, Kannan K, Colaiacovo MP. Antioxidant CoQ10 restores fertility by rescuing bisphenol A-induced oxidative DNA damage in the <i>Caenorhabditis elegans</i> Germline. Genetics 214:381-395.