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[
Journal of Gerontology,
1999]
In recent years, oxidative damage to macromolecules has gained popularity as the basis of the molecular mechanism of aging. Martin proposes oxidative damage to macromolecules as one of the major public mechanisms of aging. Interest in modifications of protein by reactive oxygen species in aging was apparently introduced by Stadtman. Although various types of oxidative modifications can occur in proteins, carbonyl residues believed to be generated by metal catalyzed reaction or otherwise introduced by lysine, arginine and/or proline residues in vivo are often used as a marker of direct or
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[
Ciba Found Symp,
1987]
Human lymphatic filariasis is caused mainly by Wuchereria bancrofti, Brugia malayi and Brugia timori. Of the estimated 90.2 million people infected, more than 90% have bancroftian and less than 10% brugian filariasis. The distribution and transmission of the disease are closely associated with socioeconomic and behavioural factors in endemic populations. Urban W. bancrofti infection, as seen in South-East Asia, is related to poor urban sanitation, which leads to intense breeding of Culex quiquefasciatus, the principal vector. Rural strains of W. bancrofti are transmitted primarily by Anopheles spp. and Aedes spp. mosquitoes. Brugian filariasis is mainly a rural disease transmitted by Mansonia, Anopheles and Aedes spp. mosquitoes. The periodic form of B. malayi is principally a human parasite, whereas the subperiodic form is zoonotically transmitted in some countries. The control of filariasis has relied on chemotherapy, vector control and reduction of human-vector contact. Although eradication of W. bancrofti and periodic B. malayi can be achieved, it is possible only to reduce transmission of zoonotic subperiodic B. malayi in some areas. A rational approach to control should consider ecological, socioeconomic and behavioural factors and, where feasible, integrate control programmes into the delivery system for primary health care.
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[
Cell,
2004]
Heterotrimeric G proteins are well known for their function in signal transduction downstream of seven transmembrane receptors. More recently, however, genetic analysis in C. elegans and in Drosophila has revealed a second, essential function of these molecules in positioning the mitotic spindle and attaching microtubules to the cell cortex. Five new publications in Cell (Afshar et al., 2004; Du and Macara, 2004 [this issue of Cell]; Hess et al., 2004), Developmental Cell (Martin-McCaffrey et al., 2004), and Current Biology (Couwenbergs et al., 2004) show that this function is conserved in vertebrates and-like the classical pathway- involves cycling of G proteins between GDP and GTP bound conformations.
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[
Journal of Gerontology,
1988]
Genetic approaches have been used to gain insights into many complex biological phenomena, but until recently most attempts to use genetic approaches to understand aging or senescence processes in metazoans have met with little success. The first review in this series (Martin and Tucker, 1988) surveyed model organisms used in the genetic analysis of aging; here I will review the analysis of life span and of the aging process by means of genetics. Problems inherent in the genetic analysis of aging will be reviewed first. Successful applications of genetics to the phenomena of aging will next be highlighted. Finally, I will present examples of ways in which both molecular and classical genetic approaches can be fruitfully and realistically applied to the study of the aging processes. Where applicable, misinterpretations and possible future directions will be noted.
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[
FASEB J,
2011]
In this contribution to the series of reflective essays celebrating the 25th anniversary of The FASEB Journal, our task is to assess the growth of research on the biology of aging during this period and to suggest where we might be heading during the next 25 yr. A review of the literature suggests a healthy acceleration of progress during the past decade, perhaps largely due to progress on the genetics of longevity of model organisms. Progress on the genetics of health span in these model organisms has lagged, however. Research on the genetic basis of the remarkable interspecific variations in life span has only recently begun to be seriously addressed. The spectacular advances in genomics should greatly accelerate progress. Research on environmental effects on life span and health span needs to be accelerated. Stochastic variations in gene expression in aging have only recently been addressed. These can lead to random departures from homeostasis during aging.-Martin, G. M. The biology of aging: 1985-2010 and beyond.
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[
East Afr Med J,
1997]
Apoptosis differs from necrosis in that no inflammatory changes occur. The understanding of apoptosis was greatly improved by the discovery of a natural model of apoptosis in Caenorhabditis elegans, a nematode worm. The study of this worm led to the discovery of two sets of genes, the prosuicide genes and the antisuicide genes which control apoptosis. Apoptosis is an active process that involves w activation of specific enzymes. The understanding of the molecular biology of apoptosis may in future lead to the availability of a potent weapon to use against cancer and to modify cell death that occurs in the neurodegenerative disorders.AD - Department of Morbid Anatomy and Forensic Medicine, Faculty of Basic Medical Sciences, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria.FAU - Olasode, B JAU - Olasode BJLA - engPT - Journal ArticlePT - ReviewPT - Review, TutorialCY - KENYATA - East Afr Med JJID - 0372766SB - IM
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[
Trends in Neurosciences,
1996]
Touch sensitivity in humans is dependent on highly specialized cutaneous nerve endings encapsulated in elaborate cellular structures such as the Pacinian, Ruffini and Meissner's corpuscles. Although the details of the encapsulations vary, the common theme involves the nerve endings making intimate mechanical linkages with the collagen-fiber networks contained within each capsule. Presumably, it is these external linkages with the membrane that serve to transmit and focus mechanical energy onto the mechanotransducers located in the nerve endings, and thus contribute to their low threshold and high mechanosensitivity. Extracellular mechanical linkages are also a feature of specific touch sensors in lower invertebrates, and thus appear to have evolved early in the animal kingdom. Indeed, it seems wherever high mechanosensitivity is required external mechanical linkages are present. In contrast, pain sensation, which is characterized by high threshold and low mechanosensitivity, is mediated by naked or free nerve endings, which lack elaborate external structures. Despite the existence of detailed ultrastructural information, the general inaccessibility of vertebrate touch and pain receptors has hampered studies on the molecules and molecular interactions underlying mechanotransduction in these cells. However, recent molecular-genetic analysis of touch-insensitive mutants in the tiny, free-swimming round worm, Caenorhabditis elegans, carried out by Martin Chalfie and colleagues, has begun to reveal detailed information on the molecular machinery of mechanotransduction. This information should provide useful clues and general principles for unravelling the molecular mechanisms underlying our own sensations of touch and pain.
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[
Endocr Metab Immune Disord Drug Targets,
2012]
Filarial infections are characterized by immunopathological phenomena, that are responsible for the onset of often dramatic pathological outcomes, such as blindness (Onchocerca volvulus) and elephantiasis (W. bancrofti). In addition, the long-term survival (as long as 10 years) of these parasites in otherwise immunocompetent hosts indicates that these nematodes are capable of manipulating the host immune response. The ground-breaking discovery of the bacterial endosymbiont Wolbachia, which resides in most filarial nematodes causing disease, has led to increasing interest in the role it may play in immuno-modulation, pro-inflammatory pathology and other aspects of filarial infection. Indeed, Wolbachia has been shown to be responsible for exacerbating inflammation (as in river blindness), while at the same time blocking efficient elimination of parasites through the host immune response (Onchocerca ochengi). While studies aimed at identifying Wolbachia as a potential target for anti-filarial therapy are at the forefront of current research, understanding its role in the immunology of filarial infection is a fascinating field that has yet to uncover many secrets.
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[
Clin Microbiol Infect,
2011]
Lymphatic filariasis (LF) and onchocerciasis are parasitic nematode infections that are responsible for a major disease burden in the African continent. Disease symptoms are induced by the immune reactions of the host, with lymphoedema and hydrocoele in LF, and dermatitis and ocular inflammation in onchocerciasis. Wuchereria bancrofti and Onchocerca volvulus, the species causing LF and onchocerciasis in Africa, live in mutual symbiosis with Wolbachia endobacteria, which cause a major part of the inflammation leading to symptoms and are antibiotic targets for treatment. The standard microfilaricidal drugs ivermectin and albendazole are used in mass drug administration programmes, with the aim of interrupting transmission, with a consequent reduction in the burden of infection and, in some situations, leading to regional elimination of LF and onchocerciasis. Co-endemicity of Loa loa with W. bancrofti or O. volvulus is an impediment to mass drug administration with ivermectin and albendazole, owing to the risk of encephalopathy being encountered upon administration of ivermectin. Research into new treatment options is exploring several improved delivery strategies for the classic drugs or new antibiotic treatment regimens for anti-wolbachial chemotherapy.
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[
Neurotoxicology,
2008]
Manganese (Mn) is a transition metal that is essential for normal cell growth and development, but is toxic at high concentrations. While Mn deficiency is uncommon in humans, Mn toxicity is known to be readily prevalent due to occupational overexposure in miners, smelters and possibly welders. Excessive exposure to Mn can cause Parkinson''s disease-like syndrome; patients typically exhibit extrapyramidal symptoms that include tremor, rigidity and hypokinesia [Calne DB, Chu NS, Huang CC, Lu CS, Olanow W. Manganism and idiopathic parkinsonism: similarities and differences. Neurology 1994;44(9):1583-6; Dobson AW, Erikson KM, Aschner M. Manganese neurotoxicity. Ann NY Acad Sci 2004;1012:115-28]. Mn-induced motor neuron diseases have been the subjects of numerous studies; however, this review is not intended to discuss its neurotoxic potential or its role in the etiology of motor neuron disorders. Rather, it will focus on Mn uptake and transport via the orthologues of the divalent metal transporter (DMT1) and its possible implications to Mn toxicity in various categories of eukaryotic systems, such as in vitro cell lines, in vivo rodents, the fruitfly, Drosophila melanogaster, the honeybee, Apis mellifera L., the nematode, Caenorhabditis elegans and the baker''s yeast, Saccharomyces cerevisiae.