Negative regulation ofUltrabithorax expression byengrailed is required for proper specification of wing development in Drosophila melanogaster

In both vertebrates and invertebrates, homeotic selector genes confer morphological differences along the antero-posterior axis. However, insect wing development is independent of all homeotic gene functions, reflecting the ground plan of an ancestral pterygote, which bore wings on all segments. Dipteran insects such asDrosophila are characterized by a pair of wings in the mesothoracic segment. In all other segments, wing development is essentially repressed by different homeotic genes, although in the metathorax they are modified into a pair of halteres. This necessitates that during development all homeotic genes are to be maintained in a repressed state in wing imaginal discs. In this report we show that (i) the function of the segment polarity geneengrailed (en) is critical to keep the homeotic selector geneUltrabithorax (Ubx) repressed in wing imaginal discs, (ii) normal levels of En in the posterior compartment of haltere discs, however, are not enough to completely repressUbx, and (iii) the repression ofUbx byen is independent of Hedgehog signalling through which the long-range signalling ofen is mediated during wing development. Finally we provide evidence for a possible mechanism by whichen repressesUbx. On the basis of these results we propose thaten has acquired two independent functions during the evolution of dorsal appendages. In addition to its well-known function of conferring posterior fate and inducing long-range signalling to pattern the developing appendages, it maintains wing fate by keepingUbx repressed

“Hey, look at me” An {auto}ethnographic account of experiencing ADHD symptoms within sport.

This auto-ethnography presents a reflective analysis of my experiences of Attention Deficit Hyperactivity Disorder (ADHD) in sport. To date, research into ADHD has been largely confined to clinical evaluation and subjective interpretations. This, however, fails to advance cultural understandings and maintains the status quo. Using an autoethnographic approach, we aim to address this in-balance within sport and to give a voice to the voiceless. As an individual diagnosed with ADHD in early childhood, the first author, guided by the second author, shares and explores his experiences as both an athlete and a coach. By endeavouring to reveal the thoughts and feelings attached to key episodes within his sporting experience, the study functions to provide preliminary evidence to showcase how ADHD can impact upon those who participate in sport. Furthermore, the vignettes presented act as a vehicle to signpost the reader in accessing the available academic literature. As a result, it is hoped that this manuscript will bring further meaning to this often misunderstood condition, showcase how ADHD symptoms may present themselves within a sporting environment, and enable coaches to support those who experience similar episodes

Creating a positive casual academic identity through change and loss

Neoliberalism has significantly impacted higher education institutes across the globe by increasing the number of casual and non-continuing academic positions. Insecure employments conditions have not only affected the well-being of contingent staff, but it has also weakened the democratic, intellectual and moral standing of academic institutions. This chapter provides one practitioner’s account of the challenges of casual work, but rather than dwelling on the negativities, it outlines the potential richness of an identity based on insecurity and uncertainty. This exploration draws on the literature of retired academics and identity theory to illustrate the potential generative spaces within an undefined and incoherent identity

Epigenetic Gene Promoter Methylation at Birth Is Associated With Child’s Later Adiposity

Objective: fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans.Research design and methods: using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5? from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ?5% and a 5–95% range ?10%, we related methylation status to maternal pregnancy diet and to child’s adiposity at age 9 years. Replication was sought in a second independent cohort.Results: in cohort 1, retinoid X receptor-? (RXRA) chr9:136355885+ and endothelial nitric oxide synthase (eNOS) chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [?] 17% per SD change in methylation [95% CI 4–31], P = 0.009, n = 64, and ? = 20% [9–32], P < 0.001, n = 66, respectively) and %fat mass (? = 10% [1–19], P = 0.023, n = 64 and ? =12% [4–20], P = 0.002, n = 66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9:136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (? = 6% [2–10] and ? = 4% [1–7], respectively, both P = 0.002, n = 239).Conclusions: our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later obesity and metabolic diseas

bantam Is Required for Optic Lobe Development and Glial Cell Proliferation

microRNAs (miRNAs) are small, conserved, non-coding RNAs that contribute to the control of many different cellular processes, including cell fate specification and growth control. Drosophila bantam, a conserved miRNA, is involved in several functions, such as stimulating proliferation and inhibiting apoptosis in the wing disc. Here, we reported the detailed expression pattern of bantam in the developing optic lobe, and demonstrated a new, essential role in promoting proliferation of mitotic cells in the optic lobe, including stem cells and differentiated glial cells. Changes in bantam levels autonomously affected glial cell number and distribution, and non-autonomously affected photoreceptor neuron axon projection patterns. Furthermore, we showed that bantam promotes the proliferation of mitotically active glial cells and affects their distribution, largely through down regulation of the T-box transcription factor, optomotor-blind (omb, Flybase, bifid). Expression of omb can rescue the bantam phenotype, and restore the normal glial cell number and proper glial cell positioning in most Drosophila brains. These results suggest that bantam is critical for maintaining the stem cell pools in the outer proliferation center and glial precursor cell regions of the optic lobe, and that its expression in glial cells is crucial for their proliferation and distribution

Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity

BACKGROUND: Acute RT-induced damage to the lung is characterized by inflammatory changes, which proceed to the development of fibrotic lesions in the late phase of injury. Ultimately, complete structural ablation will ensue, if the source of inflammatory / fibrogenic mediators and oxidative stress is not removed or attenuated. Therefore, the purpose of this study is to determine whether overexpression of extracellular superoxide dismutase (EC-SOD) in mice ameliorates acute radiation induced injury by inhibiting activation of TGFβ1 and downregulating the Smad 3 arm of its signal transduction pathway. METHODS: Whole thorax radiation (single dose, 15 Gy) was delivered to EC-SOD overexpressing transgenic (XRT-TG) and wild-type (XRT-WT) animals. Mice were sacrificed at 1 day, 1 week, 3, 6, 10 and 14 weeks. Breathing rates, right lung weights, total/differential leukocyte count, activated TGFβ1 and components of its signal transduction pathway (Smad 3 and p-Smad 2/3) were assessed to determine lung injury. RESULTS: Irradiated wild-type (XRT-WT) animals exhibited time dependent increase in breathing rates and right lung weights, whereas these parameters were significantly less increased (p < 0.05) at 3, 6, 10 and 14 weeks in irradiated transgenic (XRT-TG) mice. An inflammatory response characterized predominantly by macrophage infiltration was pronounced in XRT-WT mice. This acute inflammation was significantly attenuated (p < 0.05) in XRT-TG animals at 1, 3, 6 and 14 weeks. Expression of activated TGFβ1 and components of its signal transduction pathway were significantly reduced (p < 0.05) at later time-points in XRT-TG vs. XRT-WT. CONCLUSION: This study shows that overexpression of EC-SOD confers protection against RT-induced acute lung injury. EC-SOD appears to work, in part, via an attenuation of the macrophage response and also decreases TGFβ1 activation with a subsequent downregulation of the profibrotic TGFβ pathway

MicroRNA degradation by a conserved target RNA regulates animal behavior

International audiencemicroRNAs (miRNAs) repress target transcripts through partial complementarity. By contrast, highly complementary miRNA-binding sites within viral and artificially engineered transcripts induce miRNA degradation in vitro and in cell lines. Here, we show that a genome-encoded transcript harboring a near-perfect and deeply conserved miRNA-binding site for miR-29 controls zebrafish and mouse behavior. This transcript originated in basal vertebrates as a long noncoding RNA (lncRNA) and evolved to the protein-coding gene NREP in mammals, where the miR-29-binding site is located within the 3′ UTR. We show that the near-perfect miRNA site selectively triggers miR-29b destabilization through 3′ trimming and restricts its spatial expression in the cerebellum. Genetic disruption of the miR-29 site within mouse Nrep results in ectopic expression of cerebellar miR-29b and impaired coordination and motor learning. Thus, we demonstrate an endogenous target-RNA-directed miRNA degradation event and its requirement for animal behavio

The Sno Oncogene Antagonizes Wingless Signaling during Wing Development in Drosophila

The Sno oncogene (Snoo or dSno in Drosophila) is a highly conserved protein and a well-established antagonist of Transforming Growth Factor-β signaling in overexpression assays. However, analyses of Sno mutants in flies and mice have proven enigmatic in revealing developmental roles for Sno proteins. Thus, to identify developmental roles for dSno we first reconciled conflicting data on the lethality of dSno mutations. Then we conducted analyses of wing development in dSno loss of function genotypes. These studies revealed ectopic margin bristles and ectopic campaniform sensilla in the anterior compartment of the wing blade suggesting that dSno functions to antagonize Wingless (Wg) signaling. A subsequent series of gain of function analyses yielded the opposite phenotype (loss of bristles and sensilla) and further suggested that dSno antagonizes Wg signal transduction in target cells. To date Sno family proteins have not been reported to influence the Wg pathway during development in any species. Overall our data suggest that dSno functions as a tissue-specific component of the Wg signaling pathway with modest antagonistic activity under normal conditions but capable of blocking significant levels of extraneous Wg, a role that may be conserved in vertebrates

Week 48 resistance analyses of the once-daily, single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) >= 400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL = 3 thymidine analog-associated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response

Comparative Genomic Analysis of Drosophila melanogaster and Vector Mosquito Developmental Genes

Genome sequencing projects have presented the opportunity for analysis of developmental genes in three vector mosquito species: Aedes aegypti, Culex quinquefasciatus, and Anopheles gambiae. A comparative genomic analysis of developmental genes in Drosophila melanogaster and these three important vectors of human disease was performed in this investigation. While the study was comprehensive, special emphasis centered on genes that 1) are components of developmental signaling pathways, 2) regulate fundamental developmental processes, 3) are critical for the development of tissues of vector importance, 4) function in developmental processes known to have diverged within insects, and 5) encode microRNAs (miRNAs) that regulate developmental transcripts in Drosophila. While most fruit fly developmental genes are conserved in the three vector mosquito species, several genes known to be critical for Drosophila development were not identified in one or more mosquito genomes. In other cases, mosquito lineage-specific gene gains with respect to D. melanogaster were noted. Sequence analyses also revealed that numerous repetitive sequences are a common structural feature of Drosophila and mosquito developmental genes. Finally, analysis of predicted miRNA binding sites in fruit fly and mosquito developmental genes suggests that the repertoire of developmental genes targeted by miRNAs is species-specific. The results of this study provide insight into the evolution of developmental genes and processes in dipterans and other arthropods, serve as a resource for those pursuing analysis of mosquito development, and will promote the design and refinement of functional analysis experiments