Glial cell development and function in the Drosophila visual system

In the developing nervous system, building a functional neuronal network relies on coordinating the formation, specification and survival to diverse neuronal and glial cell subtypes. The establishment of neuronal connections further depends on sequential neuron-neuron and neuron-glia interactions that regulate cell-migration patterns and axon guidance. The visual system of Drosophila has a highly regular, retinotopic organization into reiterated interconnected synaptic circuits. It is therefore an excellent invertebrate model to investigate basic cellular strategies and molecular determinants regulating the different developmental processes that lead to network formation. Studies in the visual system have provided important insights into the mechanisms by which photoreceptor axons connect with their synaptic partners within the optic lobe. In this review, we highlight that this system is also well suited for uncovering general principles that underlie glial cell biology. We describe the glial cell subtypes in the visual system and discuss recent findings about their development and migration. Finally, we outline the pivotal roles of glial cells in mediating neural circuit assembly, boundary formation, neural proliferation and survival, as well as synaptic function.     

Importance of a pilot study for non-invasive genetic sampling: genotyping errors and population size estimation in red deer

Population size information is critical for managing endangered or harvested populations. Population size can now be estimated from non-invasive genetic sampling. However, pitfalls remain such as genotyping errors (allele dropout and false alleles at microsatellite loci). To evaluate the feasibility of non-invasive sampling (e.g., for population size estimation), a pilot study is required. Here, we present a pilot study consisting of (i) a genetic step to test loci amplification and to estimate allele frequencies and genotyping error rates when using faecal DNA, and (ii) a simulation step to quantify and minimise the effects of errors on estimates of population size. The pilot study was conducted on a population of red deer in a fenced natural area of 5440 ha, in France. Twelve microsatellite loci were tested for amplification and genotyping errors. The genotyping error rates for microsatellite loci were 0–0.83 (mean=0.2) for allele dropout rates and 0–0.14 (mean=0.02) for false allele rates, comparable to rates encountered in other non-invasive studies. Simulation results suggest we must conduct 6 PCR amplifications per sample (per locus) to achieve approximately 97% correct genotypes. The 3% error rate appears to have little influence on the accuracy and precision of population size estimation. This paper illustrates the importance of conducting a pilot study (including genotyping and simulations) when using non-invasive sampling to study threatened or managed populations.     

Alcohol consumption and mortality from all causes,coronary heart disease,and stroke: results from a prospective cohort study of Scottish men with 21 years of follow up

ObjectivesTo relate alcohol consumption to mortality.DesignProspective cohort study.Setting27 workplaces in the west of Scotland.Participants5766 men aged 35-64 when screened in 1970-3 who answered questions on their usual weekly alcohol consumption.ResultsRisk for all cause mortality was similar for non-drinkers and men drinking up to 14 units a week. Mortality risk then showed a graded association with alcohol consumption (relative rate compared with non-drinkers 1.34 (95% confidence interval 1.14 to 1.58) for 15-21 units a week, 1.49 (1.27 to 1.75) for 22-34 units, 1.74 (1.47 to 2.06) for 35 or more units). Adjustment for risk factors attenuated the increased relative risks, but they remained significantly above 1 for men drinking 22 or more units a week. There was no strong relation between alcohol consumption and mortality from coronary heart disease after adjustment. A strong positive relation was seen between alcohol consumption and risk of mortality from stroke, with men drinking 35 or more units having double the risk of non-drinkers, even after adjustment.ConclusionsThe overall association between alcohol consumption and mortality is unfavourable for men drinking over 22 units a week, and there is no clear evidence of any protective effect for men drinking less than this.

Key messages

• Results from a large cohort study of employed Scottish men showed different relations between alcohol consumption and mortality than previous studies
• There was no relation between mortality from coronary heart disease and alcohol consumption once adjustments were made for potential confounding factors
• There was a strong relation with mortality from stroke; drinkers of over 35 units a week had double the risk of mortality compared with non-drinkers
• Some but not all of this could be accounted for by alcohol related increases in blood pressure
• Overall, risk of all cause mortality was higher in men drinking 22 or more units a week

     

Molecular mechanisms of iron homeostasis

Iron metabolism in mammals requires a complex and tightly regulated molecular network. The classical view of iron metabolism has been challenged over the past ten years by the discovery of several new proteins, mostly Fe (II) iron transporters, enzymes with ferro-oxydase (hephaestin or ceruloplasmin) or ferri-reductase (Dcytb) activity or regulatory proteins like HFE and hepcidin. Furthermore, a new transferrin receptor has been identified, mostly expressed in the liver, and the ability of the megalin-cubilin complex to internalise the urinary Fe (III)-transferrin complex in renal tubular cells has been highlighted. Intestinal iron absorption by mature duodenal enterocytes requires Fe (III) iron reduction by Dcytb and Fe (II) iron transport through apical membranes by the iron transporter Nramp2/DMT1. This is followed by iron transfer to the baso-lateral side, export by ferroportin and oxidation into Fe (III) by hephaestin prior to binding to plasma transferrin. Macrophages play also an important role in iron delivery to plasma transferrin through phagocytosis of senescent red blood cell, heme catabolism and recycling of iron. Iron egress from macrophages is probably also mediated by ferroportin and patients with heterozygous ferroportin mutations develop progressive iron overload in liver macrophages. Iron homeostasis at the level of the organism is based on a tight control of intestinal iron absorption and efficient recycling of iron by macrophages. Signalling between iron stores in the liver and both duodenal enterocytes and macrophages is mediated by hepcidin, a circulating peptide synthesized by the liver and secreted into the plasma. Hepcidin expression is stimulated in response to iron overload or inflammation, and down regulated by anemia and hypoxia. Hepcidin deficiency leads to iron overload and hepcidin overexpression to anemia. Hepcidin synthesis in response to iron overload seems to be controlled by the HFE molecule. Patients with hereditary hemochromatosis due to HFE mutation have impaired hepcidin synthesis and forced expression of an hepcidin transgene in HFE deficient mice prevents iron overload. These results open new therapeutic perspectives, especially with the possibility to use hepcidin or antagonists for the treatment of iron overload disorders.     

AMPA receptors bring on the pain

The role of Ca(2+)-permeable AMPA receptors in pain processing has not been extensively studied. In this issue of Neuron, Hartmann et al. show that altering the levels of these receptors has consequences for inflammatory pain hypersensitivity but not acute pain processing.