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[
Dev Cell,
2004]
Currently, perhaps the most significant biological problem is to understand the mechanisms of learning and memory, and many of the answers will come from molecular explanations of synaptic plasticity. Two new papers have established a surprising connection: the Anaphase Promoting Complex/Cyclosome (APC/C) has a second function in controlling local protein stability at synapses, and hence in the control of behavior (Juo and Kaplan, 2004; van Roessel et al., 2004).
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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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[
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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[
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.
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[
East Afr Med J,
1994]
The nematode parasites Wuchereria bancrofti, Brugia malayi and B. timori are the causative agents of human lymphatic filariasis. Of the estimated 90 million infections world-wide, W. bancrofti is responsible for over 80 million cases and is the only known aetiologic agent in the African Region. Numbers of infected persons are on the increase world-wide due to rural-urban migrations which result in mushrooming of shanty towns often encouraging formation of favourable mosquito breeding-sites. Development of insecticide resistance by the vector mosquitoes; the toxicity and high cost of available effective formulations, and the deteriorating global economy aggravate this situation. Human lymphatic filariasis is more of a morbidity than a mortality-causing disease but can be devastating and crippling at both the individual and community levels. Unlike many parasitic infections, lymphatic filariasis can easily be controlled. The success of any control programme depends on sensitive diagnostic techniques and this is the challenge. Identification of all true positive individuals in an endemic community can be problematic since filariasis is spectral and no single diagnostic technique can be expected to be uniformly sensitive in all situations. Availability of new biotechnologies has given impetus to formulations of several diagnostic tools. New diagnostic methods and improvements on the traditional ones is the topic of this review. Recommendations in view of their field applications are also discussed.
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[
Immun Infekt,
1980]
The significance of tropical heminthiases for the populations of tropical countries is discussed and a survey on the incidence of these parasitic infections is given. The difference between infection and disease is explained, and the properties of an ideal drug for combatting the different diseases are described. After a short comment on the goals of the primary and secondary screening procedures the authors refer to WHO's Special Programme for Research and Training in Tropical Diseases. As to the different forms of filariasis, the most important problem is onchocerciasis due to the high rate of blindness. The existing drugs (suramin DEC) are evaluated, however, there is a need for a safe, macrofilaricidal drug. The chemotherapy of filariasis caused by W. bancrofti and B. malayi and the drugs used is also discussed. Thereafter, a survey on the chemotherapy of schistosomiasis and the drugs at hand and in development is given with special reference to praziquantel. Chemotherapy of opistorchiasis and clonorchiasis is still unsatisfactory. The problems arising from this situation are mentioned. Up to now, we have a similar situation in hydatid disease, caused by Echinococcus species. The therapy of choice is operation, however, in animal experiments it could be demonstrated that benzimidazole derivatives inhibit the growth of cysts what indicates the possibility of chemotherapy in man also. Finally, a survey is given on anthelminthic drugs for the therapy of different forms of intestinal helminthiasis with special regard to ancylostomiasis.
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[
Crit Rev Biochem Mol Biol,
2012]
The CCAAT box promoter element and NF-Y, the transcription factor (TF) that binds to it, were among the first cis-elements and trans-acting factors identified; their interplay is required for transcriptional activation of a sizeable number of eukaryotic genes. NF-Y consists of three evolutionarily conserved subunits: a dimer of NF-YB and NF-YC which closely resembles a histone, and the "innovative" NF-YA. In this review, we will provide an update on the functional and biological features that make NF-Y a fundamental link between chromatin and transcription. The last 25 years have witnessed a spectacular increase in our knowledge of how genes are regulated: from the identification of cis-acting sequences in promoters and enhancers, and the biochemical characterization of the corresponding TFs, to the merging of chromatin studies with the investigation of enzymatic machines that regulate epigenetic states. Originally identified and studied in yeast and mammals, NF-Y - also termed CBF and CP1 - is composed of three subunits, NF-YA, NF-YB and NF-YC. The complex recognizes the CCAAT pentanucleotide and specific flanking nucleotides with high specificity (Dorn et al., 1997; Hatamochi et al., 1988; Hooft van Huijsduijnen et al, 1987; Kim & Sheffery, 1990). A compelling set of bioinformatics studies clarified that the NF-Y preferred binding site is one of the most frequent promoter elements (Suzuki et al., 2001, 2004; Elkon et al., 2003; Marino-Ramirez et al., 2004; FitzGerald et al., 2004; Linhart et al., 2005; Zhu et al., 2005; Lee et al., 2007; Abnizova et al., 2007; Grskovic et al., 2007; Halperin et al., 2009; Hakkinen et al., 2011). The same consensus, as determined by mutagenesis and SELEX studies (Bi et al., 1997), was also retrieved in ChIP-on-chip analysis (Testa et al., 2005; Ceribelli et al., 2006; Ceribelli et al., 2008; Reed et al., 2008). Additional structural features of the CCAAT box - position, orientation, presence of multiple Transcriptional Start Sites - were previously reviewed (Dolfini et al., 2009) and will not be considered in detail here.
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[
Mutat Res,
2009]
Fanconi anemia (FA) is a severe recessive disorder with a wide range of clinical manifestations [M. Levitus, H. Joenje, J.P. de Winter, The Fanconi anemia pathway of genomic maintenance, Cell Oncol. 28 (2006) 3-29]. In humans, 13 complementation groups have been identified to underlie FA: A, B, C, D1, D2, E, F, G, I, J, L, M, and N [W. Wang, Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins, Nat. Rev. Genet. 8 (2007) 735-748]. Cells defective for any of these genes display chromosomal aberrations and sensitivity to DNA interstrand cross-links (ICLs). It has therefore been suggested that the 13 FA proteins constitute a pathway for the repair of ICLs, and that a deficiency in this repair process causes genomic instability leading to the different clinical phenotypes. However, the exact nature of this repair pathway, or even whether all 13 FA proteins are involved at some stage of a linear repair process, remains to be defined. Undoubtedly, the recent identification and characterisation of FA homologues in model organisms, such as Caenorhabditis elegans, will help facilitate an understanding of the function of the FA proteins by providing new analytical tools. To date, sequence homologues of five FA genes have been identified in C. elegans. Three of these homologues have been confirmed:
brc-2 (FANCD1/BRCA2),
fcd-2 (FANCD2), and
dog-1 (FANCJ/BRIP1); and two remain to be characterised: W02D3.10 (FANCI) and
drh-3 (FANCM). Here we review how the nematode can be used to study FA-associated DNA repair, focusing on what is known about the ICL repair genes in C. elegans and which important questions remain for the field.