Spatial heterogeneity in the radiogenic activity of the lunar interior: Inferences from CHACE and LLRI on Chandrayaan-1

In the past, clues on the potential radiogenic activity of the lunar interior have been obtained from the isotopic composition of noble gases like Argon. Excess Argon (40) relative to Argon (36), as compared to the solar wind composition, is generally ascribed to the radiogenic activity of the lunar interior. Almost all the previous estimates were based on, 'on-the-spot' measurements from the landing sites. Relative concentration of the isotopes of 40Ar and 36Ar along a meridian by the Chandra's Altitudinal Composition Explorer (CHACE) experiment, on the Moon Impact Probe (MIP) of India's first mission to Moon, has independently yielded clues on the possible spatial heterogeneity in the radiogenic activity of the lunar interior in addition to providing indicative 'antiquity' of the lunar surface along the ground track over the near side of the moon. These results are shown to broadly corroborate the independent topography measurements by the Lunar Laser Ranging Instrument (LLRI) in the main orbiter Chandrayaan-1. The unique combination of these experiments provided high spatial resolution data while indicating the possible close linkages between the lunar interior and the lunar ambience

Expression of Multiple engrailed Family Genes in Eyespots of Bicyclus anynana Butterflies Does Not Implicate the Duplication Events in the Evolution of This Morphological Novelty

Gene duplication events often create genetic redundancy that can either lead to the appearance of pseudogenes or, instead, create opportunities for the evolution of novel proteins that can take on new functions. One of the genes which has been widely studied with respect to gene duplication is engrailed (en). En-family proteins are expressed in a morphological novelty, eyespots (in the center and in the outer gold ring), in the African squinting bush brown butterfly Bicyclus anynana, as well as in a more conserved pattern, the posterior compartment of a wing. In the present study, we used whole-genome sequencing and transcriptome data to show the presence of three en-family genes and their differential expression on the pupal wings of B. anynana using in situ hybridization. The results suggest two duplication events of en-family genes, the first evidence of a two-fold duplication in the Lepidoptera. We propose that all copies initially had posterior wing compartment expression and all copies subsequently gained a novel expression domain associated with eyespot centers. Two copies secondarily lost the posterior compartment expression, and one copy alone gained the outer ring expression domain. By dating the origin of both duplication events, however, we conclude that they predate the origin of eyespots by at least 60 mya, and hence our data does not support the retention of the multiple en gene duplicates in the genome via their involvement with the novel eyespot evolutionary innovation

Optix regulates nanomorphology of butterfly scales primarily via its effects on pigmentation

Previous studies have shown that Optix regulates lower lamina thickness and the type of pigment that is produced in wing scales of a few butterfly species. However, the role of Optix in regulating pigment production across species, and in regulating additional aspects of scale morphology remains to be investigated. By combining microspectrophotometry, scanning electron microscopy, and focused ion beam technology on wild-type and Optix Bicyclus anynana crispants, we show that Optix regulates the production of orange pigments (ommochromes), represses the production of brown pigments (melanins), and regulates the morphology of the lower and upper surface of orange scales. Our findings suggest a conserved role of Optix as a switch gene that activates ommochrome and represses melanin synthesis across butterflies. By comparing these effects with other mutations, where only melanin is removed from scales, we propose that pigmentary changes, alone, affect the way that chitin polymerizes within a scale, changing lower lamina thickness as well as multiple intricate structures of the upper surface

Functional exploration of copy number alterations in a Drosophila model of triple negative breast cancer

Accounting for 10-20% of breast cancer cases, TNBC is associated with a disproportionate number of breast cancer deaths. One challenge in studying TNBC is its genomic profile: outside of TP53 loss, most cases are characterized by copy number alterations (CNAs), making modeling the disease in whole animals challenging. We computationally analyzed 186 previously identified CNA regions in breast cancer to rank genes within each region by likelihood of acting as a tumor driver. We then used a Drosophila p53-Myc TNBC model to identify 48 genes as functional drivers. To demonstrate the utility of this functional database, we established six 3-hit models; altering candidates led to increased aspects of transformation as well as resistance to the chemotherapeutic drug fluorouracil. Our work provides a functional database of CNA-associated TNBC drivers, and a template for an integrated computational/whole animal approach to identify functional drivers of transformation and drug resistance within CNAs for other tumor types

MENCA experiment aboard India’s Mars Orbiter Mission

The Mars Exospheric Neutral Composition Analyser (MENCA) aboard the Indian Mars Orbiter Mission (MOM) is a quadrupole mass spectrometer-based experiment. Making use of the highly elliptical and low inclination (~150°) orbit of MOM, MENCA will conduct in situ measurements of the composition and radial distribution of the Martian neutral exosphere in the 1–300 amu mass range in the equatorial and low latitudes of Mars. The functionality of MENCA has been tested during the Earth-bound and heliocentric phases of MOM before its operation in the Martian orbit. This article describes the scientific objectives, instrument details, design and development, test and evaluation, and calibration of the MENCA instrument

Crowdsourced identification of multi-target kinase inhibitors for RET- and TAU- based disease: the Multi-Targeting Drug DREAM Challenge

A continuing challenge in modern medicine is the identification of safer and more efficacious drugs. Precision therapeutics, which have one molecular target, have been long promised to be safer and more effective than traditional therapies. This approach has proven to be challenging for multiple reasons including lack of efficacy, rapidly acquired drug resistance, and narrow patient eligibility criteria. An alternative approach is the development of drugs that address the overall disease network by targeting multiple biological targets (‘polypharmacology’). Rational development of these molecules will require improved methods for predicting single chemical structures that target multiple drug targets. To address this need, we developed the Multi-Targeting Drug DREAM Challenge, in which we challenged participants to predict single chemical entities that target pro-targets but avoid anti-targets for two unrelated diseases: RET-based tumors and a common form of inherited Tauopathy. Here, we report the results of this DREAM Challenge and the development of two neural network-based machine learning approaches that were applied to the challenge of rational polypharmacology. Together, these platforms provide a potentially useful first step towards developing lead therapeutic compounds that address disease complexity through rational polypharmacology

γ-H2AX Kinetics as a Novel Approach to High Content Screening for Small Molecule Radiosensitizers

Persistence of γ-H2AX after ionizing radiation (IR) or drug therapy is a robust reporter of unrepaired DNA double strand breaks in treated cells.DU-145 prostate cancer cells were treated with a chemical library ±IR and assayed for persistence of γ-H2AX using an automated 96-well immunocytochemistry assay at 4 hours after treatment. Hits that resulted in persistence of γ-H2AX foci were tested for effects on cell survival. The molecular targets of hits were validated by molecular, genetic and biochemical assays and in vivo activity was tested in a validated Drosophila cancer model.We identified 2 compounds, MS0019266 and MS0017509, which markedly increased persistence of γ-H2AX, apoptosis and radiosensitization in DU-145 cells. Chemical evaluation demonstrated that both compounds exhibited structurally similar and biochemical assays confirmed that these compounds inhibit ribonucleotide reductase. DNA microarray analysis and immunoblotting demonstrates that MS0019266 significantly decreased polo-like kinase 1 gene and protein expression. MS0019266 demonstrated in vivo antitumor activity without significant whole organism toxicity.MS0019266 and MS0017509 are promising compounds that may be candidates for further development as radiosensitizing compounds as inhibitors of ribonucleotide reductase

SCIENCE FICTION

50-52The Machin

MOLECULAR MECHANISMS UNDERLYING VENATION AND COLOR PATTERNING IN BICYCLUS ANYNANA BUTTERFLIES

Ph.DDOCTOR OF PHILOSOPHY (FOS