A defect in synapsis causes male sterility in a T-DNA-tagged Arabidopsis thaliana mutant

Fluorescence microscopy was used to study meiosis in microsporocytes from wild-type Arabidopsis thaliana and a T-DNA-tagged meiotic mutant. Techniques for visualizing chromosomes and β-tubulin in other plant species were evaluated and modified in order to develop a method for analyzing meiosis in A. thaliana anthers. Like most dicots, A. thaliana microsporocytes undergo simultaneous cytokinesis in which both meiotic divisions are completed prior to cytokinesis. However, two unique events were observed in wild-type A. thaliana that have not been reported in other angiosperms: (1) polarization of the microsporocyte cytoskeleton during prophase I prior to nuclear envelope breakdown, and (2) extensive depolymerization of microtubules just prior to metaphase II. The first observation could have implications regarding a previously uncharacterized mechanism for determining the axis of the metaphase I spindle during microsporogenesis. The second observation is peculiar since microtubules are known to be involved in chromosome alignment in other species; possible explanations will be discussed. A T-DNA-tagged meiotic mutant of A. thaliana ( syn1 ), which had previously been shown to produce abnormal microspores with variable DNA content, was also cytologically characterized. The first observable defect occurs in microsporocytes at telophase I, where some chromosomes are scattered throughout the cytoplasm, usually attached to stray microtubules. Subsequent developmental stages are affected, leading to complete male sterility. Based on similarities to synaptic mutants that have been described in other species, it is suggested that this mutant is defective in synaptonemal complex formation and/or cohesion between sister chromatids.     

Charting the genetic interaction map of a cell

Genome sequencing projects have revealed a massive catalog of genes and astounding genetic diversity in a variety of organisms. We are now faced with the formidable challenge of assigning functions to thousands of genes, and how to use this information to understand how genes interact and coordinate cell function. Studies indicate that the majority of eukaryotic genes are dispensable, highlighting the extensive buffering of genomes against genetic and environmental perturbations. Such robustness poses a significant challenge to those seeking to understand the wiring diagram of the cell. Genome-scale screens for genetic interactions are an effective means to chart the network that underlies this functional redundancy. A complete atlas of genetic interactions offers the potential to assign functions to most genes identified by whole genome sequencing projects and to delineate a functional wiring diagram of the cell. Perhaps more importantly, mapping genetic networks on a large-scale will shed light on the general principles and rules governing genetic networks and provide valuable information regarding the important but elusive relationship between genotype and phenotype.     

Incidence of influenza in healthy adults and healthcare workers: a systematic review and meta-analysis

Background

Working in healthcare is often considered a risk factor for influenza; however, this risk has not been quantified. We aimed to systematically review evidence describing the annual incidence of influenza among healthy adults and healthcare workers (HCWs).

Methods and Findings

We searched OVID MEDLINE (1950 to 2010), EMBASE (1947 to 2010) and reference lists of identified articles. Observational studies or randomized trials reporting full season or annual influenza infection rates for healthy, working age adult subjects and HCWs were included. Influenza infection was defined as a four-fold rise in antibody titer, or positive viral culture or polymerase chain reaction.From 24,707 citations, 29 studies covering 97 influenza seasons with 58,245 study participants were included. Pooled influenza incidence rates (IR) (95% confidence intervals (CI)) per 100 HCWs per season and corresponding incidence rate ratios (IRR) (95% CI) as compared to healthy adults were as follows. All infections: IR 18.7 (95% CI, 15.8 to 22.1), IRR 3.4 (95% CI, 1.2 to 5.7) in unvaccinated HCWs; IR 6.5 (95% CI, 4.6 to 9.1), IRR 5.4 (95% CI, 2.8 to 8.0) in vaccinated HCWs. Symptomatic infections: IR 7.5 (95% CI, 4.9 to 11.7), IRR 1.5 (95% CI, 0.4 to 2.5) in unvaccinated HCWs, IR 4.8 (95% CI, 3.2 to 7.2), IRR 1.6 (95% CI, 0.5 to 2.7) in vaccinated HCWs.

Conclusions

Compared to adults working in non-healthcare settings, HCWs are at significantly higher risk of influenza.     

Discovery of a piperazine urea based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist

We report the discovery of piperazine urea based compound 1, a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist. Compound 1 shows anti-obesity efficacy without potentiating erectile activity in the rodent models.     

Effects of Ca(II) ions on Mn(II) dynamics in chick glia and rat astrocytes: Potential regulation of glutamine synthetase

Previous studies have demonstrated that in glia and astrocytes Mn(II) is distributed with ca. 30–40% in the cytoplasm, 60–70% in mitochondria. Ca(II) ions were observed to alter both the flux rates and distribution of Mn(II) ions in primary cultues of chick glia and rat astrocytes. External (influxing) Ca(II) ions had the greatest effect on Mn(II) uptake and efflux, compared to internal (effluxing) or internal-external equilibrated Ca(II) ions. External (influxing) Ca(II) ions inhibited the net rate and extent of Mn(II) uptake but enhanced Mn(II) efflux from mitochondria. These observations differ from Ca(II)–Mn(II) effects previously reported with brain (neuronal) mitochondria. Overall, increased cytoplasmic Ca(II) acts to block Mn(II) uptake and enhance Mn(II) release by mitochondria, which serve to increase the cytoplasmic concentration of free Mn(II). A hypothesis is presented involving external L-glutamate acting through membrane receptors to mobilize cell Ca(II), which in turn causes mitochondrial Mn(II) to be released. Because the concentration of free cytoplasmic Mn(II) is poised near the K_d for Mn(II) with glutamine synthetase, a slight increase in cytoplasmic Mn(II) will directly enhance the activity of glutamine synthetase, which catalyzes removal of neurotoxic glutamate and ammonia.     

Genetic diversity within a declining natural population of Ferocactus histrix (DC) Lindsay

Ferocactus histrix is a barrel cactus that is widespread in Mexico. A population located in Llanos de Ojuelos, a semiarid zone representative of many disturbed regions in north‐central Mexico, was studied. Over a period of 10 years (1997 to 2007), the average number of individuals decreased from 21.95 to 3.53 plants per 300 m². A change in population size structure was also registered over this period of time. In 2008, a plot selected on the basis of plant abundance was established within the population and a genetic analysis was conducted with ISTR and ISSR markers. This analysis revealed low levels of genetic diversity (expected heterozygosity (H_E) = 0.073, Shannon index (I) = 0.113 and H_E = 0.178, I = 0.271, respectively) compared with those of most studied cacti species. The genetic diversity between the different life stages was also evaluated, and a gradual decrease in levels of genetic variation was observed from adults to juveniles and seedlings (H_E = 0.130, I = 0.192 to H_E = 0.103, I = 0.157). These differences, however, were not significant. Loci fixation and a decrease in the frequency of rare alleles were observed in seedling and juvenile classes. The decline in genetic variation may be associated with recent bottlenecks experienced by the population of F. histrix. If the sizes of local populations of F. histrix continue to decrease, genetic variation will be gradually lost, and the risk of extinction will increase.     

Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders

Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR–NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the ‘pure’ forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD.