Is sleeping sickness a circadian disorder? The serotonergic hypothesis.

Patients with human African trypanosomiasis (HAT, sleeping sickness), due to the inoculation of Trypanosoma brucei gambiense or rhodesiense by the tsetse fly, are "sleepy by day and restless by night." The first 24 h polysomnographic recording (electroencephalogram [EEG], electromyogram [EMG], electrooculogram [EOG]), showing a disappearance of the 24 h rhythmicity of sleep and wakefulness, was performed in 1988. Thereafter, our team recorded 18 patients and 6 control volunteers at bed rest during 24 h sessions. Blood samples were taken hourly from 8 of the patients through a venous catheter and every 10 minutes from the remaining 10 patients. Plasma cortisol, prolactin, growth hormone (GH), melatonin, and plasma renin activity were analyzed. No disruptions of the circadian rhythms of sleep and wakefulness were described in the 6 healthy African subjects, and there also were no disturbances of 24 h hormone profiles. The patients experienced a dysregulation of the circadian rhythmicity of sleep and wakefulness that was proportional to the severity of the disease. Sleep onset rapid eye movement (REM) episodes were more frequent in the most severely sick patients, who also showed major disruptions in the 24 h plasma hormonal profiles, with intermediate profiles being observed at earlier stages of the sickness. However, the relationship between hormonal secretions and the states of vigilance persisted. Contrary to the other hormones, melatonin secretion remained undisturbed. These findings indicate that, at the stage of meningoencephalitis, HAT represents a dysregulation of the sleep-wake cycle and sleep structure, rather than a hypersomnia; this dysregulation is proportional to the degree of severity of the clinical and biological symptoms. It is accompanied by a circadian dysrhythmia of hormonal secretions, although the relationship between hormone pulses and sleep states is preserved. We therefore favor the involvement of the serotonergic raphe nuclei-suprachiasmatic nuclei liaison in the reversible disturbance of the circadian rhythms of the sleep-wake cycle and of hormonal secretions.     

The worm and the protozoa: stereotyped responses or distinct antigens?

Studies of parasitic diseases have provided the best in vivo correlates of the division of CD4+ helper T cells into distinct functional phenotypes, designated T(H)I and T(H)2, that mediate the balanced regulation of cellular and humoral immunity. In this article, Steven Reiner and Richard Locksley focus on why parasitic infections tend to generate such clearly polarized responses and emphasize that early events that mediate maturation signals towards T(H)1- or T(H)2-effector and memory cells remain incompletely defined. Effective vaccination that seeks to mold the developing immune response will need to consider the role of interleukins and various cell-surface molecules that have been identified, thus far, to influence CD4 subset differentiation.     

The 1901 uganda sleeping sickness epidemic revisited: a case of mistaken identity?

The great sleeping sickness epidemic that occurred in Busoga at the turn of the century was caused by a trypanosome identified by Bruce as Trypanosoma gambiense. A study of trypanosomes from the recent epidemic in southeast Uganda has shed new light on the origins of the disease in Busoga. Thorsten Koerner, Peter de Raadt and Ian Maudlin suggest that the epidemic of the turn of the century was of T. p. rhodesiense sleeping sickness, brought about then, as now by social upheaval.     

Guinea worm disease – the final chapter?

The global campaign for the eradication of dracunculiasis has succeeded in reducing the incidence of guinea worm disease by >99% in the past 20 years. This has been accomplished by the provision of safe drinking water supplies, filtration of drinking water, chemical control of intermediate hosts, case containment and, crucially, local health-education initiatives.     

Anhydrobiosis: the model worm as a model?

New work now shows that the dauer larvae of Caenorhabditis elegans can survive anhydrobiotically. The genetic tractability of this model organism may be useful in studying how organisms survive when losing most or all of their water.     

What does a worm want with 20,000 genes?

The number of genes predicted for the Caenorhabditis elegans genome is remarkably high: approximately 20,000, if both protein-coding and RNA-coding genes are counted. This article discusses possible explanations for such a high value.     

Invertebrate learning: what can't a worm learn?

The nematode worm Caenorhabditis elegans can learn and remember the stimuli it encounters, the environment it is in, and its own physiological state. Analyses of mutations in C. elegans that affect different aspects of experience are beginning to address the nature of learning.     

Unsegmented annelids? Possible origins of four lophotrochozoan worm taxa

In traditional classification schemes, the Annelida consists of the Polychaeta and the Clitellata (the latter including the Oligochaeta and Hirudinida). However, recent analyses suggest that annelids are much more diverse than traditionally believed, and that polychaetes are paraphyletic. Specifically, some lesser-known taxa (previously regarded as separate phyla) appear to fall within the annelid radiation. Abundant molecular, developmental, and morphological data show that the Siboglinidae, which includes the formerly recognized Pogonophora and Vestimentifera, are derived annelids; recent data from the Elongation Factor-1α (EF-1α) gene also suggest that echiurids are of annelid ancestry. Further, the phylogenetic origins of two other lesser-known groups of marine worms, the Myzostomida and Sipuncula, have recently been called into question. Whereas some authors advocate annelid affinities, others argue that these taxa do not fall within the annelid radiation. With advances in our understanding of annelid phylogeny, our perceptions of body plan evolution within the Metazoa are changing. The evolution of segmentation probably is more plastic than traditionally believed. However, as our understanding of organismal evolution is being revised, we are also forced to reconsider the specific characters being examined. Should segmentation be considered a developmental process or an ontological endpoint?     

Slipping while sleeping? Trinucleotide repeat expansions in germ cells

Trinucleotide expansions cause at least 30 diseases including Huntington's disease (HD). Many are inherited predominantly through paternal transmissions, which are probably the result of germ-cell-specific mutations. A recent study of testicular germ cells in HD patients revealed that expansions occur in diploid cells before the completion of meiosis. Therefore, expansions are not limited to the late-haploid spermatids, in which the genome is 'sleeping'. These results have implications both for research aimed at understanding the transmission of this serious mutation and for developing new therapies for the disease.     

Crisis, what crisis? Control of Rhodesian sleeping sickness

There is an urgent need for cost-effective strategies for the sustainable control of Trypanosoma brucei rhodesiense (Rhodesian) sleeping sickness, which is a fatal zoonotic disease that has caused devastating epidemics during the past century. Sleeping sickness continues to be controlled by crisis management, using active case detection, treatment and vector control - activities that occur only during major epidemics; during the intervening periods, farmers and communities must fend for themselves. There are several methods for assessing the burden of this disease and there is a series of farmer-led methodologies that can be applied to reduce the burden of human and animal trypanosomiases.     

Does the modern urbanized sleeping habitat pose a breast cancer risk?

Due to its disruptive effects on circadian rhythms and sleep deprivation at night, shiftworking is currently recognized as a risk factor for breast cancer (BC). As revealed by the present analysis based on a comparative case-control study of 1679 women, exposure to light-at-night (LAN) in the "sleeping habitat" is significantly associated with BC risk (odds ratio [OR]?=?1.220, 95% confidence interval [CI]?=?1.118-1.311; p?相似文献   

The gene genie?

Gene therapy has the potential to cure currently incurable conditions, including some cancers and inherited disorders. It might even be used in the womb to prevent congenital abnormalities. The potential was greeted with great excitement ten years ago, when gene therapy first appeared to be viable, but little progress is perceived. Just how close are we to solving the obstacles in the way of successful gene implantation / replacement?     

The initiation mess?

This review concerns the mechanisms which control initiation of chromosome replication in enterobacteria with respect to cell growth. Initiation control is commonly separated into positive and negative regulatory mechanisms. Four main points are advanced concerning these different aspects of initiation control. (i) The average concentration of the initiator protein DnaA is proportional to the origin concentration, i.e. the origin per cell mass ratio and, thus, inversely proportional to the very often used term of the 'initiation mass'. (ii) The time of initiation of chromosome replication in the cell cycle is set by DnaA protein accumulating to a threshold level, which in concert with a number of other factors allows for a co-operative formation of the initiation complex. (iii) The time of initiation is not determined by the interaction with these other factors or by the transient interaction between newly replicated origins ( oriC  ) and the cell surface. (iv) The aberrant initiation phenotype observed in various mutants, including dnaA (ts) mutants, might be due to a defective pre-initiation DnaA– oriC interaction or it might be due to a defect in the protection of newly initiated origins from reinitiation. Many of these points are discussed and evaluated in view of recent developments concerning the regulation of chromosome replication in Escherichia coli