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Science,
1984]
Within the past few years researchers have finally begun to be able to peer inside a hitherto impenetrable black box, namely, the development of complex organisms. The genes that control the commitment of embryonic cells to specific fates are now being found and characterized. A case in point is reported in this issue of Science (p. 409). Victor Ambros of Harvard University and H. Robert Horvitz of Massachusetts Institute of Technology have identified genes that affect the timing of developmental events in the roundworm Caenorhabditis elegans.
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[
2020]
Onchocerciasis, also known as the African river blindness, is the second most important cause of infectious blindness worldwide after trachoma. It is caused by the filarial nematode, <i>Onchocerca volvulus</i>, and transmitted by repeated bites of the vector, female black fly of the genus <i>Simulium damnosum</i>. The vector breeds in fast-flowing and oxygen-rich rivers in affected areas with transmission and disease prevalence usually stretching along these river basins and thereby the name river blindness.[1]Aside from blindness, onchocerciasis results in a troubling chronic dermatitis.[1]
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J Am Optom Assoc,
1993]
Onchocerciasis is commonly known as River Blindness and affects about 18 million people around the world. It is transmitted by black flies that breed in river and stream rapids and transmit the parasitic microfilariae, Onchocerca volvulus, to people who live and work near such rivers. Infection with the microfilariae results in blindness or visual impairment for 1 or 2 million people. The microfilariae migrate to superficial tissues and may invade any part of the eye and ocular structure. Living worms cause little damage, however, their death triggers a localized inflammation which can lead to blindness. Sclerosing keratitis, a severe corneal involvement, is the major cause of blindness from the disease. The World Health Organization (WHO) Expert Committee on Onchocerciasis has estimated that 9% of the disease is found in Africa, the rest occur in Yemen and Latin America. Treatment with ivermectin is contraindicated for pregnant and lactating women, children under 5 years of age, asthmatics, and people with other diseases. The WHO Onchocerciasis Control Program in 11 countries of West Africa has eliminated the risk of onchocerciasis by aerial spraying of black fly breeding sites only from 1 country. A single annual oral dose (150 mg/kg) of ivermectin can reverse early lesions in the cornea. Ivermectin must be taken annually to sustain protection against blindness, thus its incorporation into primary health care along with malaria, AIDS, trachoma, xerophthalmia, and cataract is most cost effective. Nigeria and Tanzania have optometry schools, and optometrists can play a significant role in onchocerciasis control and blindness prevention programs by training local health care workers to distribute invermectin in vision screening programs.
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[
Proteomics,
2016]
Metaproteomics--the large-scale characterization of the entire protein complement of environmental microbiota at a given point in time--has provided new features to study complex microbial communities in order to unravel these "black boxes." New technical challenges arose that were not an issue for classical proteome analytics before that could be tackled by the application of different model systems. Here, we review different current and future model systems for metaproteome analysis. Following a short introduction to microbial communities and metaproteomics, we introduce model systems for clinical and biotechnological research questions including acid mine drainage, anaerobic digesters, and activated sludge. Model systems are useful to evaluate the challenges encountered within (but not limited to) metaproteomics, including species complexity and coverage, biomass availability, or reliable protein extraction. The implementation of model systems can be considered as a step forward to better understand microbial community responses and ecological functions of single member organisms. In the future, improvements are necessary to fully explore complex environmental systems by metaproteomics.
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Insect Sci,
2016]
The Distal-less (Dll) genes are homeodomain transcription factors that are present in most Metazoa and in representatives of all investigated arthropod groups. In Drosophila, the best studied insect, Distal-less plays an essential role in forming the proximodistal axis of the legs, antennae and analia, and in specifying antennal identity. The initiation of Dll expression in clusters of cells in mid-lateral regions of the Drosophila embryo represents the earliest genetic marker of limbs. Dll genes are involved in the development of the peripheral nervous system and sensitive organs, and they also function as master regulators of black pigmentation in some insect lineages. Here we analyze the complete genomes of six insects, the nematode Caenorhabditis elegans and Homo sapiens, as well as multiple Dll sequences available in databases in order to examine the structure and protein features of these genes. We also review the function, expression, regulation, and evolution of arthropod Dll genes with emphasis on insects and spiders. This article is protected by copyright. All rights reserved.
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Clin Dermatol
]
Onchocerciasis results from infestation by the nematode Onchocerca volvulus and is characterized by troublesome itching, skin lesions, and eye manifestations. Although partially controlled by international mass prevention programs, onchocerciasis remains a major health hazard and is endemic in Africa, Arabia, and the Americas. Onchocerciasis is spread by bites from infested black flies, which transmit larvae that subsequently develop into adult filariae. Skin symptoms are commonly nonspecific and include severe pruritus, acute and chronic dermatitis, vitiligo-like hypopigmentation, and atrophy. Onchocercal ocular disease covers a large spectrum of manifestations, which in severe cases, may lead to blindness. Diagnosis is usually made by direct visualization of the larvae emerging from superficial skin biopsies, "skin snips." In some cases, the microfilariae can also be directly observed at the slit lamp when migrating into the anterior chamber of the eye. Ivermectin is, at present, the drug of choice for skin and ocular manifestations. Recent research using a chemotherapeutic approach that targets filarial Wolbachia symbionts in the treatment and control of onchocerciasis, however, suggests that 100 mg/d of doxycycline for 6 weeks might be effective in reducing the filarial load and preventing ocular symptoms.
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Front Cell Dev Biol,
2019]
Autophagy as a ubiquitous catabolic process causes degradation of cytoplasmic components and is generally considered to have beneficial effects on health and lifespan. In contrast, inefficient autophagy has been linked with detrimental effects on the organism and various diseases, such as Parkinson's disease. Previous research, however, showed that this paradigm is far from being black and white. For instance, it has been reported that increased levels of autophagy during development can be harmful, but become advantageous in the aging cell or organism, causing enhanced healthspan and even longevity. The antagonistic pleiotropy hypothesis postulates that genes, which control various traits in an organism, can be fitness-promoting in early life, but subsequently trigger aging processes later. Autophagy is controlled by the mechanistic target of rapamycin (mTOR), a key player of nutrient sensing and signaling and classic example of a pleiotropic gene. mTOR acts upstream of transcription factors such as FOXO, NRF, and TFEB, controlling protein synthesis, degradation, and cellular growth, thereby regulating fertility as well as aging. Here, we review recent findings about the pleiotropic role of autophagy during development and aging, examine the upstream factors, and contemplate specific mechanisms leading to disease, especially neurodegeneration.
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Res Rep Trop Med,
2020]
Onchocerciasis is a parasitic infection caused by the filarial nematode <i>Onchocerca volvulus</i> and transmitted through the bites of black flies of the genus <i>Similium</i> that breed in rivers and streams. The impact of mass treatment with ivermectin and supplemented by vector control in some countries has changed the global scene of onchocerciasis. There has been reported progress made in elimination of onchocerciasis in central and southern American countries and in some localities in Africa. The target for elimination in the Americas has been set at 2022 while for 12 countries in Africa this is expected in 2030. This review was conducted to examine the current status of onchocerciasis elimination at the global level and report on progress made. Literature searches were made through PubMed, articles in English or English abstracts, reports and any other relevant articles related to the subject. The global burden of onchocerciasis is progressively reducing and is no longer a public health problem in some regions. However, programs are challenged with a range of issues: cross-border transmission, diagnostic tools, <i>Loa loa</i> co-endemicity, limited workforce in entomology and maintaining enthusiasm among community drug distributors. More concerted effort using appropriate tools is required to overcome the challenges.
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[
DICP,
1990]
Ivermectin is a macrocyclic lactone (fermentation) product and actinomycete (Streptomyces avermitilis) that possesses an unusually broad spectrum of potent activity against several species of nematodes, arachnids, and insects that parasitize domestic animals. From clinical trials in humans it has been found to be microfilaricidal, killing microfilariae of Onchocerca volvulus (the parasite causing onchocerciasis), and interrupting its transmission by the black fly vector. Dermal microfilariae density in patients are reduced to near zero levels for 6-12 months after a single oral dose of ivermectin 0.15-0.2 mg/kg. Its precise mechanism of action is unknown. It has a time to maximum concentration of 2.7-4.3 h, and an elimination half-life of 28 +/- 10 h. When compared with an oral solution the tablet dosage form has a relative bioavailability of approximately 60 percent. Not much is known about its metabolism in humans, and the unchanged drug is not detected in the urine. Controlled clinical trials have shown ivermectin to be associated with milder side effects than diethylcarbamazine, the current drug of choice for onchocerciasis therapy. It does not cause the severe Mazzoti-type (anaphylactoid) reactions that are associated with diethylcarbamazine use. Ivermectin is effective, safer, and more tolerable than diethylcarbamazine. It should, therefore, replace diethylcarbamazine as the drug of choice for onchocerciasis therapy.
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Adv Exp Med Biol,
2010]
Latrophilin, a neuronal "adhesion-G protein-coupled receptor", is the major brain receptor for alpha-latrotoxin, a black widow spidertoxin which stimulates strong neuronal exocytosis in vertebrates. Latrophilin has an unusual structure consisting of two fragments that are produced by the proteolytic cleavage of the parental molecule and that behave independently in the plasma membrane. On binding an agonist, the fragments reassociate and send an intracellular signal. This signal, transduced by a heterotrimeric G protein, causes release of calcium from intracellular stores and massive release of neurotransmitters. Latrophilin represents a phylogenetically conserved family of receptors, with orthologues found in all animals and up to three homologues present in most chordate species. From mammalian homologues, latrophilins 1 and 3 are expressed in neurons, while latrophilin 2 is ubiquitous. Latrophilin 1 may control synapse maturation and exocytosis, whereas latrophilin 2 may be involved in breast cancer. Latrophilins may play different roles during development and in adult animals: thus, LAT-1 determines cell fate in early embryogenesis in Caenorhabditis elegans and controls neurotransmitter release in adult nematodes. This diversity suggests that the functions of latrophilins may be determined by their interactions with respective ligands. The finding of the ligand of latrophilin 1, the large postsynaptic protein lasso, is the first step in the quest for the physiological functions of latrophilins.