Rodriguez-Perez MA et al. (2011) Adv Parasitol "Assessment and monitoring of onchocerciasis in Latin America."

Real-Najarro O, Rodriguez-Perez MA, Unnasch TR

[Adv Parasitol, 2011]

Onchocerciasis has historically been one of the leading causes of infectious blindness worldwide. It is endemic to tropical regions both in Africa and Latin America and in the Yemen. In Latin America, it is found in 13 foci located in 6 different countries. The epidemiologically most important focus of onchocerciasis in the Americas is located in a region spanning the border between Guatemala and Mexico. However, the Amazonian focus straddling the border of Venezuela and Brazil is larger in overall area because the Yanomami populations are scattered over a very large geographical region. Onchocerciasis is caused by infection with the filarial parasite Onchocerca volvulus. The infection is spread through the bites of an insect vector, black flies of the genus Simulium. In Africa, the major vectors are members of the S. damnosum complex, while numerous species serve as vectors of the parasite in Latin America. Latin America has had a long history of attempts to control onchocerciasis, stretching back almost 100 years. The earliest programmes used a strategy of surgical removal of the adult parasites from affected individuals. However, because many of the adult parasites lodge in undetectable and inaccessible areas of the body, the overall effect of this strategy on the prevalence of infection was relatively minor. In 1988, a new drug, ivermectin, was introduced that effectively killed the larval stage (microfilaria) of the parasite in infected humans. As the microfilaria is both the stage that is transmitted by the vector fly and the cause of most of the pathologies associated with the infection, ivermectin opened up a new strategy for the control of onchocerciasis. Concurrent with the use of ivermectin for the treatment of onchocerciasis, a number of sensitive new diagnostic tools were developed (both serological and nucleic acid based) that provided the efficiency, sensitivity and specificity necessary to monitor the decline and eventual elimination of onchocerciasis as a result of successful control. As a result of these advances, a strategy for the elimination of onchocerciasis was developed, based upon mass distribution of ivermectin to afflicted communities for periods lasting long enough to ensure that the parasite population was placed on the road to local elimination. This strategy has been applied for the past decade to the foci in Latin America by a programme overseen by the Onchocerciasis Elimination Program for the Americas (OEPA). The efforts spearheaded by OEPA have been very successful, eliminating ocular disease caused by O. volvulus, and eliminating and interrupting transmission of the parasite in 8 of the 13 foci in the region. As onchocerciasis approaches elimination in Latin America, several questions still need to be addressed. These include defining an acceptable upper limit for transmission in areas in which transmission is thought to have been suppressed (e.g. what is the maximum value for the upper bound of the 95% confidence interval for transmission rates in areas where transmission is no longer detectable), how to develop strategies for conducting surveillance for recrudescence of infection in areas in which transmission is thought to be interrupted and how to address the problem in areas where the mass distribution of ivermectin seems to be unable to completely eliminate the infection.

Franz M et al. (1987) Parasitol Res "Electron-microscopic observations on the female worms of six Onchocerca species from cattle and red deer."

Copeman DB, Franz M, Schulz-Key H

[Parasitol Res, 1987]

The midbody regions of female worms of six Onchocerca species (O. flexuosa, O. tarsicola, O. lienalis, O. gutturosa, O. armillata, O. gibsoni) were studied by transmission electron microscopy. The cuticular layering was rather similar in all species with the ridges built up by the cortical layers and the inner cuticular striations by the median or basal layers. Differences in the epicuticular morphology were considerable. O. flexuosa and O. lienalis had a thin epicuticle without protuberances, the epicuticle of O. armillata carried small knobs, and O. tarsicola, O. gutturosa, and O. gibsoni had a thick trilaminar epicuticle with long protuberances. Extreme hypertrophy of hypodermis and reductions of somatic musculature were observed in O. flexuosa and O. gibsoni. Less extended thickenings of the hypodermis were observed in the other species. No degenerative alterations were found in the muscle cells of O. gutturosa and O. lienalis. The intestinal lumen of most of the species was in a central position, but in O. tarsicola and O. gibsoni the lumen was reduced to small clefts between the intestinal cells. In these species, numerous electron-dense, concentric granules were observed in the cytoplasm of the intestinal cells. The proportions of the various organs differed considerably from species to species, e.g., the uteri contained the embryos filed one behind the other in O. tarsicola, whereas 50 or more embryos were found beside one another in cross-sections of the uterus of O. gibsoni. The comparative study showed that O. gibsoni and O. volvulus have many derived morphological characteristics in common and that in the other species more primitive stages of development of these morphological marks can be observed.

Zhang S et al. (2021) Environ Pollut "Responses of Caenorhabditis elegans to various surface modifications of alumina nanoparticles"

Zhang Z, Xu Y, Mao X, Chu Q, Zhang S, Zhang M

[Environ Pollut, 2021]

The surface modifications of nanoparticles (NPs), are well-recognized parameters that affect the toxicity, while there has no study on toxicity of Al(2)O(3) NPs with different surface modification. Therefore, for the first time, this study pays attention to evaluating the toxicity and potential mechanism of pristine Al(2)O(3) NPs (p-Al(2)O(3)), hydrophilic (w-Al(2)O(3)) and lipophilic (o-Al(2)O(3)) modifications of Al(2)O(3) NPs both in vitro and in vivo. Applied concentrations of 10, 20, 40, 80,100 and 200 μg/mL for 24 h exposure on Caenorhabditis elegans (C. elegans), while 100 μg/mL of Al(2)O(3) NPs significantly decreased the survival rate. Using multiple toxicological endpoints, we found that o-Al(2)O(3) NPs (100 μg/mL) could induce more severe toxicity than p-Al(2)O(3) and w-Al(2)O(3) NPs. After uptake by C. elegans, o-Al(2)O(3) NPs increased the intestinal permeability, easily swallow and further destroy the intestinal membrane cells. Besides, cytotoxicity evaluation revealed that o-Al(2)O(3) NPs (100 μg/mL) are more toxic than p-Al(2)O(3) and w-Al(2)O(3). Once inside the cell, o-Al(2)O(3) NPs could attack mitochondria and induce the over-production of reactive oxygen species (ROS), which destroy the intracellular redox balance and lead to apoptosis. Furthermore, the transcriptome sequencing and RT-qPCR data also demonstrated that the toxicity of o-Al(2)O(3) NPs is highly related to the damage of cell membrane and the imbalance of intracellular redox. Generally, our study has offered a comprehensive sight to the adverse effects of different surface modifications of Al(2)O(3) NPs on environmental organisms and the possible underlying mechanisms.

Bain O et al. Ann Parasitol Hum Comp "[Redescription of Onchocerca gibsoni C. et J., 1910 (author's transl)]."

Bain O, Beveridge I

[Ann Parasitol Hum Comp]

O. gibsoni is redescribed; the hypoderma and the musculature of the female body are studied on transversal sections and compared to several other species of Onchocerca. These structures and the general morphology show the autonomy of a small line of asiatic and african Onchocerca of Bovines (O. gibsoni, O. dukei, O. ochengi and, probably, the other nodular Onchocerca of Bovinae), to which the human parasite, O. volvulus, belongs. The presence of O. gibsoni in Africa is doubtful.

Wang P et al. (2012) Proc Natl Acad Sci U S A "O-GlcNAc cycling mutants modulate proteotoxicity in Caenorhabditis elegans models of human neurodegenerative diseases."

Love DC, Wang P, Hanover JA, Krause MW, Lazarus BD, Forsythe ME

[Proc Natl Acad Sci U S A, 2012]

O-GlcNAcylation is an abundant posttranslational modification in the brain implicated in human neurodegenerative diseases. We have exploited viable null alleles of the enzymes of O-GlcNAc cycling to examine the role of O-GlcNAcylation in well-characterized Caenorhabditis elegans models of neurodegenerative proteotoxicity. O-GlcNAc cycling dramatically modulated the severity of the phenotype in transgenic models of tauopathy, amyloid -peptide, and polyglutamine expansion. Intriguingly, loss of function of O-GlcNAc transferase alleviated, whereas loss of O-GlcNAcase enhanced, the phenotype of multiple neurodegenerative disease models. The O-GlcNAc cycling mutants act in part by altering DAF-16-dependent transcription and modulating the protein degradation machinery. These findings suggest that O-GlcNAc levels may directly influence neurodegenerative disease progression, thus making the enzymes of O-GlcNAc cycling attractive targets for neurodegenerative disease therapies.

Cheung BHH et al. (2005) Curr Biol "Experience-dependent modulation of C. elegans behavior by ambient oxygen."

Cohen M, Rogers C, Cheung BHH, De Bono M, Albayram O

[Curr Biol, 2005]

Background: Ambient oxygen (O(2)) influences the behavior of organisms from bacteria to man. In C. elegans, an atypical O(2) binding soluble guanylate cyclase (sGC), GCY-35, regulates O(2) responses. However, how acute and chronic changes in O(2) modify behavior is poorly understood. Results: Aggregating C. elegans strains can respond to a reduction in ambient O(2) by a rapid, reversible, and graded inhibition of roaming behavior. This aerokinetic response is mediated by GCY-35 and GCY-36 sGCs, which appear to become activated as O(2) levels drop and to depolarize the AQR, PQR, and URX neurons. Coexpression of GCY-35 and GCY-36 is sufficient to transform olfactory neurons into O(2) sensors. Natural variation at the npr-1 neuropeptide receptor alters both food-sensing and O(2)-sensing circuits to reconfigure the salient features of the C. elegans environment. When cultivated in 1% O(2) for a few hours, C. elegans reset their preferred ambient O(2), seeking instead of avoiding 0%-5% O(2). This plasticity involves reprogramming the AQR, PQR, and URX neurons. Conclusions: To navigate O(2) gradients, C. elegans can modulate turning rates and speed of movement. Aerotaxis can be reprogrammed by experience or engineered artificially. We propose a model in which prolonged activation of the AQR, PQR, and URX neurons by low O(2) switches on previously inactive O(2) sensors. This enables aerotaxis to low O(2) environments and may encode a "memory" of previous cultivation in low O(2).

Wells L et al. (2001) Science "Glycosylation of nucleocytoplasmic proteins: signal transduction and O-GlcNAc."

Hart GW, Wells L, Vosseller K

[Science, 2001]

The dynamic glycosylation of serine or threonine residues on nuclear and cytosolic proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) is abundant in all multicellular eukaryotes. On several proteins, O-GlcNAc and O-phosphate alternatively occupy the same or adjacent sites, leading to the hypothesis that one function of this saccharide is to transiently block phosphorylation. The diversity of proteins modified by O-GlcNAc implies its importance in many basic cellular and disease processes. Here we systematically examine the current data implicating O-GlcNAc as a regulatory modification important to signal transduction cascades.

Wang, Peng et al. (2011) International Worm Meeting "Caenorhabditis elegans O-GlcNAc cycling mutants alter the proteotoxicity of models of human neurodegenerative disorders."

Forsythe, Michele, Wang, Peng, Lazarus, Brooke, Hanover, John, Love, Dona, Krause, Michael

[International Worm Meeting, 2011]

O-linked N-acetylglucosamine (O-GlcNAc) addition is an important post-translational modification that occurs on hundreds of proteins, including nuclear pore proteins, transcription factors, proteasome components and neuronal proteins. O-GlcNAc can be added onto and removed from serine or threonine residue by two evolutionally conserved enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. O-GlcNAcylation is abundant in the brain and it has been linked to human neurodegenerative disease. We have exploited viable null alleles of the enzymes of O-GlcNAc cycling to examine the role of O-GlcNAcylation in well-characterized C. elegans models of neurodegenerative proteotoxicity. O-GlcNAc cycling dramatically modulated the severity of the proteotoxic phenotype in transgenic models of tauopathy, b-amyloid peptide and polyglutamine expansion. Intriguingly, loss-of-function of OGT alleviated, while loss of OGA enhanced these proteotoxicity phenotype. Consistent with these observations, the O-GlcNAc cycling mutants exhibit altered stress responses and changes in the protein degradation machinery. These findings suggest that modulators of O-GlcNAc cycling may prove useful for anti-neurodegenerative disease therapies.

Dong DL et al. (1994) J Biol Chem "Purification and characterization of an O-GlcNAc selective N-acetyl-beta-D-glucosaminidase from rat spleen cytosol."

Hart GW, Dong DL

[J Biol Chem, 1994]

Glycosylation of nuclear and cytoplasmic proteins by O-linked N-acetylglucosamine (O-GlcNAc) monosaccharides is an abundant, ubiquitous, and transient post-translational modification. To characterize enzymes involved in removal of these sugars, a neutral and cytoplasmic N-acetyl-beta-D-glucosaminidase (O-GlcNAcase) with strong selectivity for O-GlcNAc-synthetic glycopeptides has been purified over 22,000-fold from rat spleen homogenate. The purified O-GlcNAcase has two major polypeptides of apparent M(r) = 54,000 (alpha subunit) and M(r) = 51,000 (beta subunit). Enzyme activity sediments at M(r) = 106,000 on sucrose gradients, indicating that the native O-GlcNAcase is an alpha beta heterodimer. The O-GlcNAcase also shows substantially stronger relative activity against O-GlcNAc-synthetic glycopeptides than other hexosaminidases. Unlike acidic lysosomal hexosaminidases, O-GlcNAcase is not inhibited by GalNAc or its analogs, has no other detectable glycosidase activities, and does not cross-react with antibodies against acidic hexosaminidases. Subcellular fractionation and latency studies demonstrate the cytoplasmic and nucleoplasmic localization of the enzyme and its ubiquitous presence in tissues. These studies suggest that O-GlcNAcase is involved in the regulated removal of O-GlcNAc from O-GlcNAc-bearing glycoproteins in the nucleoplasmic and cytoplasmic compartments of cells.

Kim J et al. (2014) Opt Express "Real-time integral imaging system for light field microscopy."

Lee B, Jung JH, Jeong Y, Hong K, Kim J

[Opt Express, 2014]

We propose a real-time integral imaging system for light field microscopy systems. To implement a 3D live in-vivo experimental environment for multiple experimentalists, we generate elemental images for an integral imaging system from the captured light field with a light field microscope in real-time. We apply the f-number matching method to generate an elemental image to reconstruct an undistorted 3D image. Our implemented system produces real and orthoscopic 3D images of micro objects in 16 frames per second. We verify the proposed system via experiments using Caenorhabditis elegans.