Genetic Interaction between Mfrp and Adipor1 Mutations Affect Retinal Disease Phenotypes

Adipor1tm1Dgen and Mfrprd6 mutant mice share similar eye disease characteristics. Previously, studies established a functional relationship of ADIPOR1 and MFRP proteins in maintaining retinal lipidome homeostasis and visual function. However, the independent and/or interactive contribution of both genes to similar disease phenotypes, including fundus spots, decreased axial length, and photoreceptor degeneration has yet to be examined. We performed a gene-interaction study where homozygous Adipor1tm1Dgen and Mfrprd6 mice were bred together and the resulting doubly heterozygous F1 offspring were intercrossed to produce 210 F2 progeny. Four-month-old mice from all nine genotypic combinations obtained in the F2 generation were assessed for white spots by fundus photo documentation, for axial length by caliper measurements, and for photoreceptor degeneration by histology. Two-way factorial ANOVA was performed to study individual as well as gene interaction effects on each phenotype. Here, we report the first observation of reduced axial length in Adipor1tmlDgen homozygotes. We show that while Adipor1 and Mfrp interact to affect spotting and degeneration, they act independently to control axial length, highlighting the complex functional association between these two genes. Further examination of the molecular basis of this interaction may help in uncovering mechanisms by which these genes perturb ocular homeostasis

Tung et al_Evolution_2018_DryadData

This .xlsx file has 9 worksheets. The name of each worksheet describes the kind of data that is in it. These are: 1. Activity data_6h_without food 2. Activity data_6h_with food 3. Activity data_24h_with food 4. Exploration data 5. Aggression data 6. Dry weight data 7. Fecundity data 8. Longevity data 9. Metabolites VB refers to the dispersal selected populations, while VBC refers to the corresponding ancestry-matched controls. Thus, VB1 and VBC1 are related to each other by ancestry, were assayed together, and therefore treated as blocks in the analysis

Epithelial mechanics are maintained by inhibiting cell fusion with age in Drosophila.

A characteristic of normal aging and age-related diseases is the remodeling of the cellular organization of a tissue through polyploid cell growth. Polyploidy arises from an increase in nuclear ploidy or the number of nuclei per cell. However, it is not known whether age-induced polyploidy is an adaption to stressors or a precursor to degeneration. Here, we find that abdominal epithelium of the adult fruit fly becomes polyploid with age through generation of multinucleated cells by cell fusion. Inhibition of fusion does not improve the lifespan of the fly, but does enhance its biomechanical fitness, a measure of the healthspan of the animal. Remarkably, Drosophila can maintain their epithelial tension and abdominal movements with age when cell fusion is inhibited. Epithelial cell fusion also appears to be dependent on a mechanical cue, as knockdown of Rho kinase, E-cadherin or α-catenin is sufficient to induce multinucleation in young animals. Interestingly, mutations in α-catenin in mice result in retina pigment epithelial multinucleation associated with macular disease. Therefore, we have discovered that polyploid cells arise by cell fusion and contribute to the decline in the biomechanical fitness of the animal with age

Mechanism of Resistance to Camptothecin, a Cytotoxic Plant Secondary Metabolite, by Lymantria sp. Larvae

Camptothecin (CPT), a monoterpene indole alkaloid, is a potent inhibitor of eukaryotic topoisomerase I (Top 1). Because of this property, several derivatives of CPT are widely used as chemotherapeutic agents. The compound is produced by several plant species, including Nothapodytes nimmoniana (Family: Icacinaceae) presumably as a deterrent to insect pests. Here, we report, a lepidopteran larva, Lymantria sp. of Lymantriidae family which feeds voraciously on the leaves of N. nimmoniana, without any adverse consequences. Larval body weight and molting period were unaffected despite captive feeding of the larva with CPT enriched leaves. Mass spectrometric analysis indicated that nearly 46% of the ingested CPT was excreted while the rest was sequestered predominantly in the exuviae and setae (~35%). Although most of the CPTwas in the parental form as found in the plant, traces of inactive, sulfated forms of CPT were recovered from the larva. Compared to that in plant, there were no critical mutations at the CPT binding domain of the insect’s Top 1. The gut pH of the larva was alkaline (pH 10.0). The alkaline gut environment converts CPT from its active, lactone form to inactive, carboxylate form. It is likely that such conversion might help the larva to reduce the overall burden of CPT in its gut. We discuss the results in the context of the mechanisms of resistance adapted by insects to plant toxins

OPLS-DA analysis for S<i>u</i> and I<i>u</i> treatments.

<p>OPLS-DA (a) score plot and (b) loading plot derived from ¹H NMR spectra of S<i>u</i> and I<i>u</i> treatments, with the section above 0 in the loading plot representing metabolites higher in the I<i>u</i> treatment and the section below 0 in the loading plot representing metabolites higher in the S<i>u</i> treatment and (c) S-line plot visualizing differences between I<i>u</i> and S<i>u</i> populations.</p

Current Views on Chr10q26 Contribution to Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in the global aging population. Familial aggregation and genome-wide association (GWA) studies have identified gene variants associated with AMD, implying a strong genetic contribution to AMD development. Two loci, on human Chr 1q31 and 10q26, respectively, represent the most influential of all genetic factors. While the role of CFH at Chr 1q31 is well established, uncertainty remains about the genes ARMS2 and HTRA1, at the Chr 10q26 locus. Since both genes are in strong linkage disequilibrium, assigning individual gene effects is difficult. In this chapter, we review current literature about ARMS2 and HTRA1 and their relevance to AMD risk. Future studies will be necessary to unravel the mechanisms by which they contribute to AMD

OPLS-DA analysis to see the effect of bacterial infection.

<p>(a) OPLS-DA score plot for I<i>i</i>-I<i>u</i> comparison, (b) OPLS-DA score plot for S<i>i</i>-S<i>u</i> comparison, (c) S-line plot for I<i>i</i>-I<i>u</i> comparison and (d) S-line plot for S<i>i</i>-S<i>u</i> comparison.</p

Experimental design for the NMR metabolomics experiments.

<p>Four independent blocks, each having two regimes I and S were subjected to three treatments. Each treatment had 5 replicates.</p

OPLS-DA analysis for S<i>u</i> and I<i>u</i> treatments.

<p>OPLS-DA (a) score plot and (b) loading plot derived from ¹H NMR spectra of S<i>u</i> and I<i>u</i> treatments, with the section above 0 in the loading plot representing metabolites higher in the I<i>u</i> treatment and the section below 0 in the loading plot representing metabolites higher in the S<i>u</i> treatment and (c) S-line plot visualizing differences between I<i>u</i> and S<i>u</i> populations.</p

Polar dendrogram.

<p>Polar dendrogram showing differences between all the I treatments (I<i>u</i>, I<i>i</i> and I<i>s</i>) and all the S treatments (S<i>u</i>, S<i>i</i> and S<i>s</i>). Each treatment is an average of five replicates with each replicate consisting of 20 flies.</p