Microsporidiosis: human diseases and diagnosis

Microsporidia are considered opportunistic pathogens in humans because they are most likely to cause diseases if the immune status of a host is such that the infection cannot be controlled. A wide spectrum of diseases has been reported among persons infected with microsporidia and different diagnostic techniques have been developed during the last decade.     

Vesical Dysfunction Due to Prolapsed Disc

Neural disturbance of micturition may occur as a result of a prolapsed intervertebral disc. Single nerve root lesions are unlikely to cause bladder dysfunction; a massive central protrusion producing total blockage of the vertebral canal or multiple disc lesions are more likely to cause disturbance of voiding. High lesions are more prone to cause severe bladder dysfunction. Vesical dysfunction may sometimes be present without the typical back and leg pain.Provided a gynaecological cause is excluded, any young or middle-aged woman developing incontinence and retention with a sterile urine must be fully investigated to exclude a disc lesion. Once the disc has been removed, bladder function will improve, but in some cases recovery will be slow. Rarely some patients have permanent bladder dysfunction following a disc operation.     

Global measles elimination

Measles remains a leading vaccine-preventable cause of child mortality worldwide, particularly in sub-Saharan Africa where almost half of the estimated 454,000 measles deaths in 2004 occurred. However, great progress in measles control has been made in resource-poor countries through accelerated measles-control efforts. The global elimination of measles has been debated since measles vaccines were first licensed in the 1960's, and this debate is likely to be renewed if polio virus is eradicated. This review discusses the pathogenesis of measles and the likelihood of the worldwide elimination of this disease.     

Coral reef bleaching in the 1980s and possible connections with global warming

Scleractinian corals and their symbiotic dinoflagellate algae build massive, wave-resistant coral reefs that are pre-eminent in shallow tropical seas. This mutualism is especially sensitive to numerous environmental stresses, and has been disrupted frequently during the past decade. Increased seawater temperatures have been proposed as the most likely cause of coral reef bleaching, and it has been suggested that the recent large-scale disturbances are the first biological indication of global warming. This article describes recent bleaching events and their possible link with sea warming and other environmental stresses, and offers some speculation on the fate of coral reefs if the Earth enters a sustained period of warming.     

Ragweed – An allergy risk in Sweden?

Ragweed pollen, which is a major cause of allergic rhinitis in North America and during the last decades, also in parts of the European continent, has not been regarded as a risk in Sweden, since occurrences of Ambrosia have been rare and with two exceptions, ephemeral. During the last four years, however, long-distance transported pollen has been registered in South Sweden. Moreover, seeds are dispersed by man with birdseed and reports on ragweed plants growing at birdtables are becoming more and more common. In warm years, the fruits of these plants mature and are germinative. We argue that there is a risk that ragweed pollen may be a problem in the future in Sweden. Long-distance transport from the continent is likely to be increasingly more common, and in larger amounts, as ragweed is rapidly spreading in Europe. Among the plants now appearing within Sweden, selection is likely to favour phenotypes which are able to fulfil their life-cycle during the indigenous vegetation period, especially in a scenario of global warming.     

Genetics and conservation biology

Conservation genetics encompasses genetic management of small populations, resolution of taxonomic uncertainties and management units, and the use of molecular genetic analyses in forensics and to understanding species' biology. The role of genetic factors in extinctions of wild populations has been controversial, but evidence now shows that they make important contributions to extinction risk. Inbreeding has been shown to cause extinctions of wild populations, computer projections indicate that inbreeding depression has important effects on extinction risk, and most threatened species show signs of genetic deterioration. Inappropriate management is likely to result if genetic factors are ignored in threatened species management.     

Lipoprotein lipase deficiency resulting from a nonsense mutation in exon 3 of the lipoprotein lipase gene.

The gene for erythroid 5-aminolevulinate synthase has been mapped to Xpter-Xq26 by Southern blot hybridization analysis of a mouse/human hybrid cell panel. In situ hybridization maps the gene to Xp21-Xq21, with the most likely location being on band Xp11.2. The mapping of the erythroid 5-amino-levulinate synthase gene to the X chromosome suggests that a defect in this gene may be the primary cause of X-linked sideroblastic anemia.     

Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes

A central challenge in interpreting personal genomes is determining which mutations most likely influence disease. Although progress has been made in scoring the functional impact of individual mutations, the characteristics of the genes in which those mutations are found remain largely unexplored. For example, genes known to carry few common functional variants in healthy individuals may be judged more likely to cause certain kinds of disease than genes known to carry many such variants. Until now, however, it has not been possible to develop a quantitative assessment of how well genes tolerate functional genetic variation on a genome-wide scale. Here we describe an effort that uses sequence data from 6503 whole exome sequences made available by the NHLBI Exome Sequencing Project (ESP). Specifically, we develop an intolerance scoring system that assesses whether genes have relatively more or less functional genetic variation than expected based on the apparently neutral variation found in the gene. To illustrate the utility of this intolerance score, we show that genes responsible for Mendelian diseases are significantly more intolerant to functional genetic variation than genes that do not cause any known disease, but with striking variation in intolerance among genes causing different classes of genetic disease. We conclude by showing that use of an intolerance ranking system can aid in interpreting personal genomes and identifying pathogenic mutations.     

Mind your teeth—The relationship between mastication and cognition

This article explores the multifactorial relationship between mastication and cognition, with a focus on dementia. Older persons, especially those with dementia, are at great risk of suffering from oral health problems such as orofacial pain and loss of natural teeth. A possible explanation could be that the cognitive and motor impairments resulting from dementia cause a decrease in self‐care and as such, a worsening of oral health. An alternative explanation is that cognition and oral health influence each other. Animal studies show that a decrease in masticatory activity, for example, due to a soft diet or loss of teeth, causes memory loss and neuronal degeneration. The relationship between mastication and cognition has also been researched in human studies, but a cause‐effect relationship has not been proven. It is likely that multiple factors play a role in this relationship, such as self‐care, nutrition, stress and pain.     

Effect of the G375C and G346E achondroplasia mutations on FGFR3 activation

Two mutations in FGFR3, G380R and G375C are known to cause achondroplasia, the most common form of human dwarfism. The G380R mutation accounts for 98% of the achondroplasia cases, and thus has been studied extensively. Here we study the effect of the G375C mutation on the phosphorylation and the cross-linking propensity of full-length FGFR3 in HEK 293 cells, and we compare the results to previously published results for the G380R mutant. We observe identical behavior of the two achondroplasia mutants in these experiments, a finding which supports a direct link between the severity of dwarfism phenotypes and the level and mechanism of FGFR3 over-activation. The mutations do not increase the cross-linking propensity of FGFR3, contrary to previous expectations that the achondroplasia mutations stabilize the FGFR3 dimers. Instead, the phosphorylation efficiency within un-liganded FGFR3 dimers is increased, and this increase is likely the underlying cause for pathogenesis in achondroplasia. We further investigate the G346E mutation, which has been reported to cause achondroplasia in one case. We find that this mutation does not increase FGFR3 phosphorylation and decreases FGFR3 cross-linking propensity, a finding which raises questions whether this mutation is indeed a genetic cause for human dwarfism.     

The rare-male effect: what is its evolutionary significance?

Negatively frequency-dependent male mating success, the rare-male effect (RME), has been reported from many laboratory experiments, particularly with Drosophila spp. Problems with observer bias, lack of repeatability, with experimental design and with the analysis of data may indicate that the RME is considerably less well documented than has been supposed, even in the laboratory. Male competition is unlikely to be a common cause of the RME, except where there are behavioural differences between competing strains that result in lower competition between them than within them. A mixture of fixed female preferences seems the most likely cause, and further behavioural studies are required to investigate this mechanism. There is no convincing evidence that the RME is a consequence of frequency-dependent female preferences. An RME in the absence of negative assortment is not in general expected to lead to the avoidance of inbreeding because matings between relatives will not be reduced. Nor is it likely to contribute to the high levels of genetic polymorphism found in nature, because females would be required to base their mating preferences on genotypes at all or most loci, to show individual variation in respect of their preferences and to sum the information into an index of genomic rarity. Given the levels of polymorphism involved, all males are likely to be rare by some criterion. A varying direction of female preference, required for a two-sided RME and for the maintenance of genetic polymorphism, has yet to be reported from wild populations. The RME is therefore probably of limited evolutionary significance. Disassortative mating with respect to self-incompatibility alleles in plants, and possibly major histocompatibility complex (MHC) alleles in vertebrates, results in an RME, inbreeding avoidance and high levels of genetic polymorphism at these loci.     

Molecular characterization of ura1, a mutant allele for orotidine-5'-monophosphate decarboxylase in Schizophyllum commune

Abstract The basis of the auxotrophic ural phenotype in Schizophyllum commune has been investigated. Two point mutations causing changes in conserved amino acid positions 62 (from lysine to glutamate) and 79 (from leucine to phenylalanine) most likely are the cause for the observed phenotype, whereas the overall gene structure was unchanged. Since reversion rates in this locus are extremely low, a single point mutation could not be expected to be the cause for the mutation. Besides the two point mutations expected to be induced by UV mutagenesis, the two alleles investigated from independently isolated strains differ by approximately 7% in nucleic acid sequence and about 3% in amino acid sequence, indicating a distant relationship between the strains used.     

Extinctions of herbivorous mammals in the late Pleistocene of Australia in relation to their feeding ecology: No evidence for environmental change as cause of extinction

Abstract There has been debate over the cause of the extinction of ‘megafauna’ species during the late Pleistocene of Australia. One view is that environmental change, either natural or human‐induced, was the main factor in the extinctions. Some support for this comes from the observation that, among herbivores, most of the species that went extinct were apparently browsers rather than grazers. Browsers would presumably have been more dependent on shrubland and woodland habitats than grazers, and it has been argued that such habitats might have contracted in response to aridity or changed fire regimes in the late Pleistocene. Here, we test this idea by comparing extinction rates of browsers and grazers in the late Pleistocene, controlling for body mass in both groups. We show that in both browsers and grazers the probability of extinction was very strongly related to body mass, and the body mass at which extinction became likely was similar in the two groups. It is true that more browsers than grazers went extinct, but this is largely because most very large herbivores in the late Pleistocene were browsers, not because large browsers were more likely to go extinct than similarly sized grazers. This result provides evidence against some forms of environmental change as a cause of the extinctions.     

Idiopathic Neonatal Hepatitis: Discordance in Monozygotic Twins

Idiopathic neonatal hepatitis is the uncommon syndrome of prolonged obstructive jaundice associated with giant cell transformation in the liver and patent bile ducts. Either hepatitis virus or an inherited abnormality has been suggested as a likely pathogenic agent for the syndrome.Recent observation of discordance for idiopathic neonatal hepatitis in monozygotic twins is felt to be inconsistent with either an infectious or a simple genetic etiology. Immaturity of the hepatic parenchymal cell bilirubin excretory pathway is postulated as a cause of jaundice in some of these babies.     

Positively supercoiled plasmid DNA is produced by treatment of Escherichia coli with DNA gyrase inhibitors.

A procedure has been developed whereby the relative amounts of the topoisomers of E. coli plasmid can be determined for cells grown under a variety of conditions. Several applications of the procedure are presented. Addition of either novobiocin or oxolinic acid, two inhibitors of DNA gyrase, gives rise to positively supercoiled plasmid. A likely model for the introduction of positive supercoils, involving DNA gyrase itself, is discussed. Oxolinic acid is also shown to induce linearization of plasmid in vivo. Starvation of cells for ATP is shown to cause relaxation of plasmid. The shift of a gyrB temperature-sensitive strain to the restrictive temperature is also shown to cause plasmid relaxation. Finally, it is noted that polyamine starvation of E. coli has no detectable effect on the distribution of topoisomers.     

Repiratory muscle dysfunction in sepsis

It became evident in the past 12 years that venitlatory muscle contractile performance is significantly impaired during the course of septic shock. In animal models of septic shock, depression of ventilatory muscle contractile performance has been shown to cause hypercapneic ventilatory failure and respiratory arrest. Failure of ventilatory muscle contractility in septic shock has never been attributed to a single factor, but two groups of factors are likely to be involved: (a) increased ventilatory muscle metabolic demands due to augmentation of ventilation, hypoxemia and increased pulmonary impedance; and (b) specific cellular, metabolic, immune and hemodynamic defects which interfere with several processes necessary for normal force generation. These defects are mediated by complex interactions between several local and systematic mediator such a bacterial endotoxin, proinflammatory cytokines, prostaglandins, platelet activating factor, reactive oxygen species and nitric oxide. This is a summary of how these interactions are likely to interfere with ventilatory muscle contractile performance in septic shock with particular emphasis on the newly described role of nitric oxide.     

A device to estimate the light gradients relevant to phototropism in the laboratory and the field

An apparatus has been devised to measure the irradiance falling on a central point from each of 48 points of the compass. The apparatus has been used to estimate the magnitude and spatial distribution of light gradients in a variety of situations which are known to cause phototropism.
Measurements show that the typical laboratory treatments used to induce phototropism produce extreme light gradients which are not typical of the light gradients likely to be experienced by seedlings growing in the natural environment. Diffuse light which is always present in the natural environment, ensures that all flanks of seedlings will be subject to potentially physiologically significant light stimulation. Such findings need to be taken into account when devising and testing models of phototropic detection in plants.     

The Science and Philosophy of a Method for Assessing Environmental Causes

When an environmental impairment has been identified, it becomes necessary to identify the cause so that an appropriate action can be planned. However, causation is difficult to establish—both conceptually and in practice. To ensure that the U.S. Environmental Protection Agency's (USEPA's) method for causal assessment is appropriate and defensible, we reviewed concepts of causation from philosophers, statisticians, epidemiologists, and others. This article summarizes the results of that review and explains how it relates to the USEPA's method. We include a five-step process: (1) identify alternative candidate causes; (2) logically eliminate when possible; (3) diagnose when possible; (4) analyze the strength of evidence for remaining candidate causes; and (5) identify the most likely cause. We also encourage three practices: (1) use a consistent process; (2) do not claim proof of causation; and (3) document the evidence and inferences. This approach allows assessors to identify the most likely cause or, failing that, to reduce the set of possible causes and identify information needs for another iteration of causal assessment.