The receptor tyrosine kinase regulator sprouty1 is a target of the tumor suppressor WT1 and important for kidney development

WT1 encodes a transcription factor involved in kidney development and tumorigenesis. Using representational difference analysis, we identified a new set of WT1 targets, including a homologue of the Drosophila receptor tyrosine kinase regulator, sprouty. Sprouty1 was up-regulated in cell lines expressing wild-type but not mutant WT1. WT1 bound to the endogenous sprouty1 promoter in vivo and directly regulated sprouty1 through an early growth response gene-1 binding site. Expression of Sprouty1 and WT1 overlapped in the developing metanephric mesenchyme, and Sprouty1, like WT1, plays a key role in the early steps of glomerulus formation. Disruption of Sprouty1 expression in embryonic kidney explants by antisense oligonucleotides reduced condensation of the metanephric mesenchyme, leading to a decreased number of glomeruli. In addition, sprouty1 was expressed in the ureteric tree and antisense-treated ureteric trees had cystic lumens. Therefore, sprouty1 represents a physiologically relevant target gene of WT1 during kidney development.

Sex differences in heritability of BMI: A comparative study of results from twin studies in eight countries

Body mass index (BMI), a simple anthropometric measure, is the most frequently used measure of adiposity and has been instrumental in documenting the worldwide increase in the prevalence of obesity witnessed during the last decades. Although this increase in overweight and obesity is thought to be mainly due to environmental changes, i.e., sedentary lifestyles and high caloric diets, consistent evidence from twin studies demonstrates high heritability and the importance of genetic differences for normal variation in BMI. We analysed self-reported data on BMI from approximately 37,000 complete twin pairs (including opposite sex pairs) aged 20-29 and 30-39 from eight different twin registries participating in the GenomEUtwin project. Quantitative genetic analyses were conducted and sex differences were explored. Variation in BMI was greater for women than for men, and in both sexes was primarily explained by additive genetic variance in all countries. Sex differences in the variance components were consistently significant. Results from analyses of opposite sex pairs also showed evidence of sex-specific genetic effects suggesting there may be some differences between men and women in the genetic factors that influence variation in BMI. These results encourage the continued search for genes of importance to the body composition and the development of obesity. Furthermore, they suggest that strategies to identify predisposing genes may benefit from taking into account potential sex specific effects.

Relative importance of female-specific and non-female-specific effects on variation in iron stores between women

Women have lower iron stores than men because of iron loss during their reproductive years. However, variation between women could result from differences in iron loss, aspects of iron homeostasis common to men and women, or a combination of both. We compared the effects of age, menopause, menstrual blood loss and the number of pregnancies (sex-specific factors), and the effects of genetic variation, on markers of iron stores. We assessed how much the same genes or other familial factors influence iron status in both men and women. Data from 2039 female twins who participated in studies of reproductive health and iron status were used to estimate the proportions of variation that could be ascribed to genes, environment and measured factors. Significant effects of age, menopausal status and magnitude of menstrual blood loss were demonstrated, accounting for up to 18% of variance in serum ferritin in this sample, but number of children had no significant effect. Genetic effects were more than twice as great as sex-specific effects. The within-pair similarity of ferritin values in dizygotic female twin pairs was greater than for dizygotic opposite-sex pairs, but this difference was not quite significant, consistent with a minor role for sex-specific factors; and the opposite-sex within-pair differences did not diminish significantly with age. We conclude that the contribution of genetic differences between women to variation in iron stores outweighs the comparatively small effects of interindividual variation in iron loss through variation in menstruation and number of pregnancies.

Role of China in the quest to define and control severe acute respiratory syndrome

China holds the key to solving many questions crucial to global control of severe acute respiratory syndrome (SARS). The disease appears to have originated in Guangdong Province, and the causative agent, SARS coronavirus, is likely to have originated from an animal host, perhaps sold in public markets. Epidemiologic findings, integral to defining an animal-human linkage, may be confirmed by laboratory studies; once animal host(s) are confirmed, interventions may be needed to prevent further animal-to-human transmission. Community seroprevalence studies may help determine the basis for the decline in disease incidence in Guangdong Province after February 2002. China will also be able to contribute key data about how the causative agent is transmitted and how it is evolving, as well as identifying pivotal factors influencing disease outcome.

Potential role of head lice, Pediculus humanus capitis, as vectors of Rickettsia prowazekii

Since the pioneering work of Charles Nicolle in 1909 [see Gross (1996) Proc Natl Acad Sci USA 93:10539-10540] most medical officers and scientists have assumed that body lice are the sole vectors of Rickettsia prowazekii, the aetiological agent of louse-borne epidemic typhus (LBET). Here we review the evidence for the axiom that head lice are not involved in epidemics of LBET. Laboratory experiments demonstrate the ability of head lice to transmit R. prowazekii, but evidence for this in the field has not been reported. However, the assumption that head lice do not transmit R. prowazekii has meant that head lice have not been examined for R. prowazekii during epidemics of LBET. The strong association between obvious (high) infestations of body lice and LBET has contributed to this perception, but this association does not preclude head lice as vectors of R. prowazekii. Indeed, where the prevalence and intensity of body louse infections may be high (e.g. during epidemics of LBET), the prevalence and intensity of head louse infestations is generally high as well. This review of the epidemiology of head louse and body louse infestations, and of LBET, indicates that head lice are potential vectors of R. prowazekii in the field. Simple observations in the field would reveal whether or not head lice are natural vectors of this major human pathogen.

Recent advances on the role of CD40 and dendritic cells in immunity and tolerance

CD40 is a key signaling pathway for the function of B cells, monocytes, and dendritic cells in the immune system, and plays an important role in inflammatory pathways of nonhemopoietic cells. The NFkappaB family of transcription factors is a critical mediator in inflammation. NFkappaB is involved both in the regulation of CD40 expression and in cell signaling after CD40 ligation. This positive feedback loop linking NFkappaB and CD40 plays an important role in the control of the adaptive immune response, with fundamental implications for immunity and tolerance in vivo.

Expression of Pax258 in the gastropod statocyst: insights into the antiquity of metazoan geosensory organs

Most animals have sensory systems that allow them to balance and orient relative to the pull of gravity. Structures responsible for these functions range from very simple statocysts found in many aquatic invertebrates to the complex inner ear of mammals. Previous studies suggest that the specialized mechanosensory structures responsible for balance in vertebrates and insects may be homologous based on the requirement and expression of group II Pax genes (i.e., Pax-2/5/8 genes). Here we report the expression of a Pax-258 gene in the statocysts and other chemosensory and mechanosensory cells during the development of the gastropod mollusk Haliotis asinina, a member of the Lophotrochozoa. Based on the phylogenetic distribution of geo-sensory systems and the consistent expression of Pax-258 in the cells that form these systems, we propose that Pax-258, along with POU-III and -IV genes, has an ancient and conserved role in the formation of structures responsible for balance and geotaxis in eumetazoans.

Seeking SOCS and sex steroids

In seeking to explain why oral estrogen inhibits the GH-IGF-I axis, a recent study has unearthed a new way that steroid hormones can influence growth hormone action. This involves suppressors of cytokine signalling (SOCS), which offer a new level of understanding in signal control and crosstalk.

A longitudinal analysis of sex differences in bone mineral accrual in healthy 8-19-year-old boys and girls

Background: Although early in life there is little discernible difference in bone mass between boys and girls, at puberty sex differences are observed. It is uncertain if these differences represent differences in bone mass or just differences in anthropometric dimensions. Aim: The study aimed to identify whether sex independently affects bone mineral content (BMC) accrual in growing boys and girls. Three sites are investigated: total body (TB), femoral neck (FN) and lumbar spine (LS). Subjects and methods: 85 boys and 67 girls were assessed annually for seven consecutive years. BMC was assessed by dual energy X-ray absorptiometry (DXA). Biological age was defined as years from age at peak height velocity (PHV). Data were analysed using a hierarchical (random effects) modelling approach. Results: When biological age, body size and body composition were controlled, boys had statistically significantly higher TB and FN BMC at all maturity levels (p < 0.05). No independent sex differences were found at the LS (p > 0.05). Conclusion: Although a statistical significant sex effect is observed, it is less than the error of the measurement, and thus sex difference are debatable. In general, sex difference are explained by anthropometric difference

Structure of the HERG K+ channel S5P extracellular linker - Role of an amphipathic alpha-helix in C-type inactivation

The HERG K+ channel has very unusual kinetic behavior that includes slow activation but rapid inactivation. These features are critical for normal cardiac repolarization as well as in preventing lethal ventricular arrhythmias. Mutagenesis studies have shown that the extracellular peptide linker joining the fifth transmembrane domain to the pore helix is critical for rapid inactivation of the HERG K+ channel. This peptide linker is also considerably longer in HERG K+ channels, 40 amino acids, than in most other voltage-gated K+ channels. In this study we show that a synthetic 42-residue peptide corresponding to this linker region of the HERG K+ channel does not have defined structural elements in aqueous solution; however, it displays two well defined helical regions when in the presence of SDS micelles. The helices correspond to Trp(585)-Ile(593) and Gly(604)-Tyr(611) of the channel. The Trp(585)-Ile(593) helix has distinct hydrophilic and hydrophobic surfaces. The Gly(604)-Tyr(611) helix corresponds to an N-terminal extension of the pore helix. Electrophysiological studies of HERG currents following application of exogenous S5P peptides show that the amphipathic helix in the S5P linker interacts with the pore region of the channel in a voltage-dependent manner.

Ichthyotoxicity of Chattonella marina (Raphidophyceae) to damselfish (Acanthochromis polycanthus): the synergistic role of reactive oxygen species and free fatty acids

This investigation aimed to elucidate the relative roles of putative brevetoxins, reactive oxygen species and free fatty acids as the toxic principle of the raphidophyte Chattonella marina, using damselfish as the bioassay. Our investigations on Australian C. marina demonstrated an absence or only very low concentrations of brevetoxin-like compounds by radio-receptor binding assay and liquid chromatography-mass spectroscopy techniques. Chattonella is unique in its ability to produce levels of reactive oxygen species 100 times higher than most other algal species. However, high levels of superoxide on their own were found not to cause fish mortalities. Lipid analysis revealed this raphidophyte to contain high concentrations of the polyunsaturated fatty acid eicosapentaenoic acid (EPA; 18-23% of fatty acids), which has demonstrated toxic properties to marine organisms. Using damselfish as a model organism, we demonstrated that the free fatty acid (FFA) form of EPA produced a mortality and fish behavioural response similar to fish exposed to C. marina cells. This effect was not apparent when fish were exposed to other lipid fractions including a triglyceride containing fish oil, docosahexaenoate-enriched ethyl ester, or pure brevetoxin standards. The presence of superoxide together with low concentrations of EPA accelerated fish mortality rate threefold. We conclude that the enhancement of ichthyotoxicity of EPA in the presence of superoxide can account for the high C. marina fish killing potential. (C) 2003 Elsevier B.V All rights reserved.

Systematic review of the role of pre-oxygenation for tracheal suctioning in ventilated newborn infants

Pre-oxygenation for endotracheal suctioning for mechanically ventilated infants is routine practice in many neonatal intensive care units. In the present systematic review the evidence to support its use is discussed and the authors conclude that no confident recommendations can be made from the results of this review.