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Increasing reports suggest insulin signalling pathway as a putative drug target against polyglutamine [poly(Q)] disorders, such as Huntington's disease (HD), Spinocerebellar ataxias (SCA) 1, 2, 3 etc. However, studies on drug-based stimulation of insulin signalling cascade to mitigate poly(Q) pathogenesis are lacking. In our study, we adopted an evidence-based approach to examine if some established insulin stimulating drug can be utilized to restrict poly(Q) aetiology in Drosophila disease models. For the first time, we report that glipizide, an FDA approved anti-diabetic drug upregulates insulin signalling in poly(Q) expressing tissues and restricts formation of inclusion bodies and neurodegeneration. Moreover, it reinstates the chromatin architecture by improving histone acetylation, which is otherwise abrogated due to poly(Q) toxicity. In view of the functional conservation of insulin signalling pathway in Drosophila and humans, our finding strongly suggests that glipizide can be repurposed as an effective treatment strategy against the neurodegenerative poly(Q) disorders. Also, with appropriate validation studies in mammalian disease models, glipizide could be subsequently considered for the clinical trials in human patients. • Glipizide upregulates insulin signalling in human poly(Q) expressing tissues in Drosophila. • Glipizide restricts formation of poly(Q) aggregates and neurodegeneration. • Glipizide improves histone acetylation and reinstate chromatin architecture in poly(Q) expressing cells. • Glipizide may be repurposed to restrict pathogenesis of human poly(Q) disorders. [ABSTRACT FROM AUTHOR]

Abstract We theoretically investigate the transport properties of a normal-insulator-superconductor (NIS) junction of silicene in the thin barrier limit. Similar to graphene the tunneling conductance in such NIS structure exhibits an oscillatory behavior as a function of the strength of the barrier in the insulating region. However, unlike in graphene, the tunneling conductance in silicene can be controlled by an external electric field owing to its buckled structure. We also demonstrate the change in behavior of the tunneling conductance across the NIS junction as we change the chemical potential in the normal silicene region. In addition, at high doping levels in the normal region, the period of oscillation of the tunneling conductance as a function of the barrier strength changes from π / 2 to π with the variation of doping in the superconducting region of silicene. Highlights • Tunneling conductance (TC) exhibits contrasting behavior in various doping regimes. • Unlike in graphene, TC in silicene shows strong dependence on electric field. • Electric field acts as a switch to tune the conductance from on to off condition. • Unusual doping dependence of period of oscillation of TC vs the barrier strength. [ABSTRACT FROM AUTHOR]

Hemoglobins (Hbs) are evolutionarily conserved small globular proteins with characteristic 3-over-3 α-helical sandwich structure that is typically known as “globin fold”. Hbs have been found to be involved in diverse biological functions and the characteristic property of oxygen transportation is relatively a recent adaptation. Drosophila genome possesses three globin genes ( glob1 , glob2, and glob3 ) and it was previously reported that adequate expression of glob1 is required for various aspects of development, and also to regulate the cellular level of reactive oxygen species (ROS). The present study illustrates the explicit role of glob1 gene in Drosophila development. We demonstrate a dynamic expression pattern of glob1 in larval tissues which largely concentrate around F-actin rich structures and also co-precipitate. Reduced expression of glob1 leads to developmental abnormalities which appeared to be largely mediated by inappropriately formed F-actin based cytoskeletal structures. Our subsequent analysis in FLP/FRT mediated somatic clones establishes specific role of Drosophila glob1 in maintenance of the integrity of F-actin based cytoskeleton during development. For the first time, we report interaction between Glob1 and actin, and propose a novel role of glob1 in maintenance of F-actin based cytoskeleton in Drosophila. [ABSTRACT FROM AUTHOR]

Abstract: Polyglutamine or poly(Q) disorders are dominantly inherited neurodegenerative diseases characterised by progressive loss of neurons in cerebellum, basal ganglia and cortex in adult human brain. Overexpression of human form of mutant SCA3 protein with 78 poly(Q) repeats leads to the formation of inclusion bodies and increases the cellular toxicity in Drosophila eye. The present study was directed to identify a genetic modifier of poly(Q) diseases that could be utilised as a potential drug target. The initial screening process was influenced by the fact of lower prevalence of cancer among patients suffering with poly(Q) disorders which appears to be related to the intrinsic biological factors. We investigated if Drosophila Myc (a homologue of human cMyc proto-oncogene) harbours intrinsic property of suppressing cellular toxicity induced by an abnormally long stretch of poly(Q). We show for the first time that targeted overexpression of Drosophila Myc (dMyc) mitigates the poly(Q) toxicity in eye and nervous systems. Upregulation of dMyc results in a significant reduction in accumulation of inclusion bodies with residual poly(Q) aggregates localising into cytoplasm. We demonstrate that dMyc mediated suppression of poly(Q) toxicity is achieved by alleviating the cellular level of CBP and improved histone acetylation, resulting restoration of transcriptional machinery which are otherwise abbreviated due to poly(Q) disease conditions. Moreover, our study also provides a rational justification of the enigma of poly(Q) patients showing resistance to the predisposition of cancer. [Copyright &y& Elsevier]

Neurogenesis is driven by spatially and temporally regulated proliferation of neuronal progenitor cells that generates enormous number of assorted neurons to drive the complex behavior of an organism. Drosophila nervous system provides an advantageous model for identification and elucidation of the functional significance of the novel gene(s) involved in neurogenesis. The present study attempts to investigate the role(s) of globin1 (glob1) in the development and maintenance of the nervous system in Drosophila. It is increasingly clear now that globin genes play important role(s) in the various biological phenomena. The vertebrate neuroglobin has been reported to profoundly express in neuronal tissues and provides neuroprotection. We noted ubiquitous presence of Glob1 in the developing neuronal tissues with enhanced concentration throughout the VNC which comprises of midline cell clusters, which subsequently forms numerous types of progenitor cells and finally differentiate into specific neurons of the nervous system. Ubiquitous or pan-neuronal downregulation of glob1 causes partial lethality and mis-positioning of various neural-progenitor cells present in the embryonic midline cell clusters. Subsequently, profound expression of Glob1 was noted in the outer proliferation center of larval brain and photoreceptor axons of optic stalk. The overall arrangement of photoreceptor axons and stereotype positioning of neuroblast cells present in the central region of the brain were severally affected due to reduced expression of glob1. In addition, such larvae and surviving adults develop significant neuro-muscular disabilities. For the first time, our study suggests a novel role of glob1 in development and maintenance of the nervous system adding a new dimension to the functional significance of the multi-tasking glob1 gene in Drosophila. • Glob1 expresses profoundly in VNC during embryogenesis. • OPC and OS of larval brain exhibit enhanced level of Glob1. • Depletion in the expression of glob1 causes mispositioning of various neuronal precursor cells. • Downregulation of glob1 results in neuromuscular disabilities. [ABSTRACT FROM AUTHOR]