-
[
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.
-
[
Annual Review of Biophysics & Bioengineering,
1984]
Many questions about the action of muscle would be answered if we knew the atomic structures of both myosin and actin. The analysis of complete myosin genes and the sequencing of amino acids are vital steps towards this end. Genetic analysis identifies the different variants of myosin that exist in each animal, and the study of mutants will help to distinguish essential parts of the molecule. New cloned genes with changed functions will soon be constructed. The amino acid sequence places the important active groups and structural units of this very large protein in their correct framework. It also helps to show how the individual molecules form into regular arrays in the thick filaments of muscle. Under the electron miscroscope, individual myosin molecules appear to have long, thin rodlike tails with two globular heads emerging in a forked configuration at one end. Each molecule is a doublet containing two, paired myosin chains. The rod part is approximately 1500 A long and 20 A in diameter, while the heads are elongated, with a diameter of 70 A and length of up to 200 A. The main protein subunit of myosin is called the heavy chain. The
unc-54 gene heavy chain from the soil nematode worm Caenorhabditis elegans contains 1966 amino acids (Figures 1 and 2). Figure 1 also shows part of M. Elzinga's chemical sequence from the head of rabbit skeletal muscle for comparison. The rod sequence from nematode alone contains 7-residue and 28-residue repeats, so it is laid out in zones of 28 amino acids with its own local numbering system (1' to 1117') indicated in the rest of this article by primes. Other sequences and special features marked in the Figures are described later. This review concentrates on structural aspects of muscle, excluding chemical kinetics and the dynamics of contraction. We begin with a short account of basic facts. Next we consider the myosin genes and the topography of the active regions in the head. An analysis of regularities in the rod sequence then leads on to questions about thick filaments packing and the mechanical flexibility of the
-
[
Trends Cell Biol,
2009]
Cilia are organelles that project from most eukaryotic organisms and cell types. Their pervasiveness stems from having remarkably versatile propulsive and sensory functions, which in humans are recognized to have essential roles in physiology and development. Under-appreciated, however, are their diverse ultrastructures and typically bipartite organization consisting of doublet and singlet microtubules. Moreover, the overall shapes of the membrane-ensheathed cilia are varied, as exemplified by differences between hair-like olfactory cilia and rod- or cone-shaped photoreceptor connecting cilia-outer segments. Although cell-specific transcriptional programs are evidently crucial in establishing ciliary morphological specialization, few players directly involved in generating such diversity are known. Recent findings suggest that at least two molecular motors (kinesin-II and OSM-3/KIF17) can differentially mobilize the intraflagellar transport machinery required for ciliogenesis and, presumably, different cargo to help generate dynamic, structurally and functionally distinct cilia.
-
[
BioEssays,
1999]
The remarkable order of striated muscle is the result of a complex series of protein interactions at different levels of organization. Within muscle, the thick filament and its major protein myosin are classical examples of functioning protein machines. Our understanding of the structure and assembly of thick filaments and their organization into the regular arrays of the A-band has recently been enhanced by the application of biochemical, genetic, and structural approaches. Detailed studies of the thick filament backbone have shown that the myosins are organized into a tubular structure. Additional protein machines and specific myosin rod sequences have been identified that play significant roles in thick filament structure, assembly, and organization. There include intrinsic filament components, cross-linking molecules of the M-band and constituents of the membrane-cytoskeleton system. Muscle organization is directed by the multistep actions of protein machines that take advantage of well-established self-assembly relationships.
-
[
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
-
[
Vision Res,
2012]
The mechanism by which myristoylated proteins are targeted to specific subcellular membrane compartments is poorly understood. Two novel acyl-binding proteins, UNC119A and UNC119B, have been shown recently to function as chaperones/co-factors in the transport of myristoylated G protein -subunits and src-type tyrosine kinases. UNC119 polypeptides feature an immunoglobulin-like -sandwich fold that forms a hydrophobic pocket capable of binding lauroyl (C12) and myristoyl (C14) side chains. UNC119A in rod photoreceptors facilitates the transfer of transducin subunits (T) from inner segment to outer segment membranes by forming an intermediate diffusible UNC119-T complex. Similar complexes are formed in other sensory neurons, as the G proteins ODR-3 and GPA-13 in Caenorhabditis elegans
unc-119 mutants traffic inappropriately. UNC119B knockdown in IMCD3 cells prevents trafficking ofmyristoylated nephrocystin-3 (NPHP3), a protein associated with nephronophthisis, to cilia. Further, UNC119A was shown to transport myristoylated src-type tyrosine kinases to cell membranes and to affect T-cell receptor (TCR) and interleukin-5 receptor (IL-5R) activities. These interactions establish UNC119 polypeptides as novel lipid-binding chaperones with specificity for a diverse subset of myristoylated proteins.
-
[
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.
-
[
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.
-
[
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.
-
[
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.