Krishnamoorthy K et al. (1991) Indian J Med Res "Influence of diethylcarbamazine on the patent period of infection in periodic Brugia malayi."

Sabesan S, Panicker KN, Vanamail P, Krishnamoorthy K

[Indian J Med Res, 1991]

The patent period of infection which reflects the fecundic life span of the adult female worm was estimated for periodic B. malayi in south India by using immigration death model. Longitudinal data on natural loss of infection or that due to different degrees of DEC pressure in a cohort population of microfilaria carriers after a three years period, were used for the estimations. The patent period of infection was estimated to be 3.45 yr under natural conditions (without DEC therapy), which was reduced to 1.67 yr following one full course of selective therapy (6 mg/kg body wt/day for 12 days). When selective therapy was supplemented with four rounds of biannual single-dose mass DEC therapy (6 mg/kg body wt) the patent period was further reduced to 1.34 yr. The proportion loss of infection was relatively higher in microfilaria carriers who discontinued DEC selective therapy, when compared to natural loss. The percentage reduction in the mean microfilaria count was observed to decrease with increasing DEC pressure. Neither sex nor the age of the host was found to influence the fecundic life span or the survival of female adult worm.

Kocherscheidt L et al. (2010) Pediatr Allergy Immunol "Cytokine and chemokine responses in adults, newborns and children exposed to Entamoeba histolytica/dispar, Onchocerca volvulus and Plasmodium falciparum."

Agossou A, Hamm DM, Soboslay PT, Gantin RG, Banla M, Kocherscheidt L

[Pediatr Allergy Immunol, 2010]

Cytokine and chemokine response profiles were studied in newborns, 10-yr-old children and post partum mothers. All study groups were repeatedly exposed to Entamoeba histolytica, Onchocerca volvulus and Plasmodium falciparum infections as indicated by their Immunoglobulin (IgG) responses to parasite-specific antigens. As key indicators for regulatory and pro-inflammatory cytokine and chemokine responses, Interferon (IFN)gamma and regulatory IL-10 were investigated, along with the chemokines MIP-1 alpha/CCL3, MIP-1 beta/CCL4, MDC/CCL22 and TARC/CCL17. Entamoeba histolytica antigens (EhAg) strongly activated pro-inflammatory MIP-1 alpha/CCL3 and MIP-1 beta/CCL4 responses of similar magnitude in mothers, children and neonates alike. Plasmodium falciparum antigens (PfAg) enhanced MIP-1 alpha/CCL3, MIP-1 beta/CCL4 and MDC/CCL22 production in neonates, but did not trigger these chemokines in mothers or 10-yr-old children. Onchocerca volvulus antigens (OvAg) activated IFN-gamma and TARC/CCL17 production in mothers but not in neonates and children. Crude IL-10 production [i.e., without subtracting spontaneous cellular release (baseline)] was highest in mothers and somewhat lower in neonates, while the lowest IL-10 amounts of all were released by peripheral blood mononuclear cells from 10-yr-old children. In summary, strong inflammatory chemokine responses to plasmodia and ameba antigens in newborns and 10-yr-old children suggest that adequately balanced immune regulatory mechanisms may not have developed yet in these age groups and that repeated exposure to parasite infections and immune maturation during childhood is required to generate similar cytokine and chemokine profiles as in adults.

Cupp EW et al. (2005) Am J Trop Med Hyg "Short report: impact of ivermectin community-level treatments on elimination of adult Onchocerca volvulus when individuals receive multiple treatments per year."

Cupp EW, Cupp MS

[Am J Trop Med Hyg, 2005]

A reanalysis of several published reports indicates that when community-wide biannual treatment disrupts transmission of new infection, a profound macrofilaricidal effect of ivermectin (Mectizan) occurs that is accelerated for individuals treated 4 times a year (4x/yr). The effect is particularly obvious on adult male worms and suggests that this gender is susceptible to repetitive treatment after transmission has been blocked or greatly reduced as a result of community treatment.

Salih F et al. (2008) J Biomol Struct Dyn "Sequence structure of hidden 10.4-base repeat in the nucleosomes of C. elegans."

Salih F, Trifonov EN, Salih B

[J Biomol Struct Dyn, 2008]

By measuring prevailing distances between YY, YR, RR, and RY dinucleotides in the large database of the nucleosome DNA fragments from C. elegans, the consensus sequence structure of the nucleosome DNA repeat of C. elegans was reconstructed: (YYYYYRRRRR)(n). An actual period was estimated to be 10.4 bases. The pattern is fully consistent with the nucleosome DNA patterns of other eukaryotes, as established earlier, and, thus, the YYYYYRRRRR repeat can be considered as consensus nucleosome DNA sequence repeat across eukaryotic species. Similar distance analysis for [A, T] dinucleotides suggested the related pattern (TTTYTARAAA)(n) where the TT and AA dinucleotides display rather out of phase behavior, contrary to the "AA or TT" in-phase periodicity, considered in some publications. A weak 5-base periodicity in the distribution of TA dinucleotides was detected.

Zhang A et al. (2024) J Gerontol A Biol Sci Med Sci "Characterization of effects of mTOR inhibitors on aging in C. elegans."

Nguyen Hong C, Kern CC, Gems D, Garcia GM, Chapman H, Zhang A, Xie P, Zhang B

[J Gerontol A Biol Sci Med Sci, 2024]

Pharmacological inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway with rapamycin can extend lifespan in several organisms. Although this includes the nematode Caenorhabditis elegans, effects in this species are relatively weak and sometimes difficult to reproduce. Here we test effects of drug dosage and timing of delivery to establish the upper limits of its capacity to extend life, and investigate drug effects on age-related pathology and causes of mortality. Liposome-mediated rapamycin treatment throughout adulthood showed a dose-dependent effect, causing a maximal 21.9% increase in mean lifespan, but shortening of lifespan at the highest dose, suggesting drug toxicity. Rapamycin treatment of larvae delayed development, weakly reduced fertility and modestly extended lifespan. By contrast, treatment initiated later in life robustly increased lifespan, even from day 16 (or ~70 yr in human terms). The rapalog temsirolimus extended lifespan similarly to rapamycin, but effects of everolimus were weaker. As in mouse, rapamycin had mixed effects on age-related pathologies, inhibiting one (uterine tumor growth) but not several others, suggesting a segmental antigeroid effect. These findings should usefully inform future experimental studies with rapamycin and rapalogs in C. elegans.

Norman KR et al. (2002) J Cell Biol "Alpha spectrin is essential for morphogenesis and body wall muscle formation in Caenorhabditis elegans."

Moerman DG, Norman KR

[J Cell Biol, 2002]

A common feature of multicellular animals is the ubiquitous presence of the spectrin cytoskeleton. Although discovered over 30 yr ago, the function of spectrin in nonerythrocytes has remained elusive. We have found that the spc-1 gene encodes the only alpha spectrin gene in the Caenorhabditis elegans genome. During embryogenesis, a spectrin localizes to the cell membrane in most if not all cells, starting at the first cell stage. Interestingly, this localization is dependent on beta spectrin but not beta(Heavy) spectrin. Furthermore, analysis of spc-1 mutants indicates that beta spectrin requires a spectrin to be stably recruited to the cell membrane. Animals lacking functional a spectrin fail to complete embryonic elongation and die just after hatching. These mutant animals have defects in the organization of the hypodermal apical actin cytoskeleton that is required for elongation. in addition, we find that the process of elongation is required for the proper differentiation of the body wall muscle. Specifically, when compared with myofilaments in wild-type animals the myofilaments of the body wall muscle in mutant animals are abnormally oriented relative to the longitudinal axis of the embryo, and the body wall muscle cells do not undergo normal cell shape changes.

Barranco D et al. (2022) Cryobiology "Long-term cryostorage does not negatively affect the recovery of Caenorhabditis elegans."

Risco R, Barranco D

[Cryobiology, 2022]

Cryostorage of Caenorhabditis elegans nematodes is important to maintain the many lines used for research. The standard method uses 15% of glycerol in M9-Buffer and a cooling rate of 1 C/min; then worms can be stored in a -80 C freezer or in liquid nitrogen. The recovery of C. elegans from stocks stored in liquid nitrogen is reported to be in the range of 35-45% and slightly decreases after years of storage. The storage at -80 C is also considered safe, but the recovery is not as high as in liquid nitrogen. These observations have not been experimentally reported and therefore require verification. In this study, the standard methods were used in a set of experiments to compare the recovery of larvae and adult worms stored at -80 C or in liquid nitrogen, after short- (a week) or long-term storage (3.5 years). No differences were observed in recovery, either for the time of storage or for the temperature of storage. Recovery of larvae was 32% at -80 C and 36% in liquid nitrogen after 3.5 yr and that was not significantly different from the 7-d recovery rates. Adult worm recovery was below 5% for all treatments. These results suggest that both methods of storage can be used to successfully store C. elegans larvae for at least 3.5 years.

Cesbron JY et al. (1988) J Immunol "Onchocerca volvulus. Monoclonal anti-idiotype antibody as antigen signal for the microfilaricidal cytotoxicity of diethylcarbamazine-treated platelets."

Cesbron JY, Hayasaki M, Capron A, Lutsch C, Grzych JM, Joseph M

[J Immunol, 1988]

Over the past 35 yr, diethylcarbamazine (DEC) has been the most widely used agent for the treatment of filarial diseases, particularly in onchocerciasis. The microfilaricidal action of DEC has been recently shown to be mediated by blood platelets with the additional triggering of a filarial excretory Ag (FEA). This FEA could be detected by using mAb in the serum of infected patients. By using one mAb (IA2(23] directed against Onchocerca volvulus and recognizing circulating Ag (Ab1), we purified by affinity chromatography the target molecule of IA2(23) (an O. volvulus glycoprotein recognized by IA2(23) mAb). This compound had a dose-dependent effect on the cytotoxic action of DEC-treated platelets. We subsequently produced an anti-idiotype mAb to Ab1 (Ab2), and considered the possibility of replacing the O. volvulus glycoprotein recognized by IA2(23) mAb by Ab2. Ab2 was selected according to its ability to inhibit the binding of radioiodinated Ab1 to the filarial target Ag. It induced the production of anti-O. volvulus antibodies (Ab3) in rats. At a constant concentration of DEC platelets, the addition of increasing amounts of Ab2 led to a dose-dependent cytotoxic effect against parasite larvae. Experiments performed with Ab2 on detergent solubilized surface proteins of platelets identified four bands of Mr 18, 26, 43.5, and 100 kDa, supporting the idea of the presence of binding sites on the platelets for a FEA required for the microfilaricidal cytotoxicity of DEC-treated platelets.

Fridolfsson HN et al. (2012) FASEB J "Mitochondria-localized caveolin in adaptation to cellular stress and injury."

Moreno AL, Balijepalli RC, Okada H, Patel HH, Insel PA, Fridolfsson HN, Ross RS, Lesnefsky EJ, Ali SS, Jennings M, Niesman IR, Chen Q, Patel PM, Head BP, Miyanohara A, Kellerhals SE, Migita MY, Kawaraguchi Y, Roth DM, Kidd MW, Finley JC, Bonds JA, Panneerselvam M

[FASEB J, 2012]

We show here that the apposition of plasma membrane caveolae and mitochondria (first noted in electron micrographs >50 yr ago) and caveolae-mitochondria interaction regulates adaptation to cellular stress by modulating the structure and function of mitochondria. In C57Bl/6 mice engineered to overexpress caveolin specifically in cardiac myocytes (Cav-3 OE), localization of caveolin to mitochondria increases membrane rigidity (4.2%; P<0.05), tolerance to calcium, and respiratory function (72% increase in state 3 and 23% increase in complex IV activity; P<0.05), while reducing stress-induced generation of reactive oxygen species (by 20% in cellular superoxide and 41 and 28% in mitochondrial superoxide under states 4 and 3, respectively; P<0.05) in Cav-3 OE vs. TGneg. By contrast, mitochondrial function is abnormal in caveolin-knockout mice and Caenorhabditis elegans with null mutations in caveolin (60% increase free radical in Cav-2 C. elegans mutants; P<0.05). In human colon cancer cells, mitochondria with increased caveolin have a 30% decrease in apoptotic stress (P<0.05), but cells with disrupted mitochondria-caveolin interaction have a 30% increase in stress response (P<0.05). Targeted gene transfer of caveolin to mitochondria in C57Bl/6 mice increases cardiac mitochondria tolerance to calcium, enhances respiratory function (increases of 90% state 4, 220% state 3, 88% complex IV activity; P<0.05), and decreases (by 33%) cardiac damage (P<0.05). Physical association and apparently the transfer of caveolin between caveolae and mitochondria is thus a conserved cellular response that confers protection from cellular damage in a variety of tissues and settings.

Schulenburg H et al. (2017) Genetics "The Natural Biotic Environment of Caenorhabditis elegans."

Felix MA, Schulenburg H

[Genetics, 2017]

Organisms evolve in response to their natural environment. Consideration of natural ecological parameters are thus of key importance for our understanding of an organism's biology. Curiously, the natural ecology of the model species Caenorhabditis elegans has long been neglected, even though this nematode has become one of the most intensively studied models in biological research. This lack of interest changed 10 yr ago. Since then, an increasing number of studies have focused on the nematode's natural ecology. Yet many unknowns still remain. Here, we provide an overview of the currently available information on the natural environment of C. elegans We focus on the biotic environment, which is usually less predictable and thus can create high selective constraints that are likely to have had a strong impact on C. elegans evolution. This nematode is particularly abundant in microbe-rich environments, especially rotting plant matter such as decomposing fruits and stems. In this environment, it is part of a complex interaction network, which is particularly shaped by a species-rich microbial community. These microbes can be food, part of a beneficial gut microbiome, parasites and pathogens, and possibly competitors. C. elegans is additionally confronted with predators; it interacts with vector organisms that facilitate dispersal to new habitats, and also with competitors for similar food environments, including competitors from congeneric and also the same species. Full appreciation of this nematode's biology warrants further exploration of its natural environment and subsequent integration of this information into the well-established laboratory-based research approaches.