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Formation of Neurofibrillary Tangles (NFTs) in neuronal tissues has been implicated as the hallmark of disease pathogenesis and tau mediated toxicity in human and mammalian models. However, previous studies had failed to correlate NFT formation with pathogenesis of human neuronal tauopathies in Drosophila disease models. Though, a recent report suggests formation of tau mediated NFTs like structures confined to dopaminergic neurons in Drosophila adult brain; by utilizing various approaches, we demonstrate distinct and recurrent formation of NFTs in Drosophila neuronal tissues upon expression of wild type or mutant isoforms of human tau protein, and this appears as the key mediator of the pathogenesis of human neuronal tauopathy in Drosophila . Further, we show that tissue specific downregulation of dMyc ( Drosophila homolog of human c-myc proto-oncogene) alleviates h-tau mediated cellular and functional deficits by restricting the formation of NFTs in neuronal tissues. Therefore, our findings provide very critical and novel insights about pathogenesis of human neuronal tauopathies in Drosophila disease models. [ABSTRACT FROM AUTHOR]

Human neurodegenerative polyglutamine [poly(Q)] disorders, such as Huntington's disease (HD) and spinocerebellar ataxias (SCA), are characterised by an abnormal expansion of CAG repeats in the affected gene. The mutated proteins misfold and aggregate to form inclusion bodies that sequester important factors involved in cellular transcription, growth, stress and autophagic response and other essential functions. The insulin signalling pathway has been demonstrated as a major modifier and a potential drug target to ameliorate the poly(Q) mediated neurotoxicity in various model systems. Insulin signalling cascade harbours several downstream sub-pathways, which are synergistically involved in discharging indispensable biological functions such as growth and proliferation, metabolism, autophagy, regulation of cell death pathways etc. Hence, it is difficult to conclude whether the mitigation of poly(Q) neurotoxicity is an accumulative outcome of the insulin cascade, or the result of a specific sub-pathway. For the first time, we report that the ligand binding domain of insulin receptor mediated downstream growth promoting sub-pathway plays the pivotal role in operating the rescue event. We show that the growth promoting activity of insulin cascade is essential to minimize the abundance of inclusion bodies, to restrict neurodegeneration, and to restore the cellular transcriptional balance. Subsequently, we noted the involvement of the mTOR/S6k/4E-BP candidates in mitigating poly(Q) mediated neurotoxicity. Due to the conserved cellular functioning of the insulin cascade across species, and availability of several growth promoting molecules, our results in Drosophila poly(Q) models indicate towards a possibility of designing novel therapeutic strategies to restrict the pathogenesis of devastating human poly(Q) disorders. [Display omitted] • Ligand binding domain of insulin receptor mediates downstream growth promoting branch of insulin signalling in Drosophila. • Growth promoting sub-pathway of insulin signalling is essential to confer rescue against poly(Q) disorders. • Growth promotion is mediated by S6k/4E-BP to restore chromatin architecture and transcriptional balance. • Our study may potentially aid in designing of a novel therapeutic strategy against poly(Q) disorders. [ABSTRACT FROM AUTHOR]

Human tauopathies represent a group of neurodegenerative disorders, characterized by abnormal hyperphosphorylation and aggregation of tau protein, which ultimately cause neurodegeneration. The aberrant tau hyperphosphorylation is mostly attributed to the kinases/phosphatases imbalance, which is majorly contributed by the generation of reactive oxygen species (ROS). Globin(s) represent a well-conserved group of proteins which are involved in O 2 management, regulation of cellular ROS in different cell types. Similarly, Drosophila globin1 (a homologue of human globin) with its known roles in oxygen management and development of nervous system exhibits striking similarities with the mammalian neuroglobin. Several recent evidences support the hypothesis that neuroglobins are associated with Alzheimer's disease pathogenesis. We herein noted that targeted expression of human-tau induces the cellular level of Glob1 protein in Drosophila tauopathy models. Subsequently, RNAi mediated restored level of Glob1 restricts the pathogenic effect of human-tau by minimizing its hyperphosphorylation via GSK-3β/p-Akt and p-JNK pathways. In addition, it also activates the Nrf2-keap1-ARE cascade to stabilize the tau-mediated increased level of ROS. These two parallel cellular events provide a significant rescue against human tau-mediated neurotoxicity in the fly models. For the first time we report a direct involvement of an oxygen sensing globin gene in tau etiology. In view of the fact that human genome encodes for the multiple Globin proteins including a nervous system specific neuroglobin; and therefore, our findings may pave the way to investigate if the conserved oxygen sensing globin gene(s) can be exploited in devising novel therapeutic strategies against tauopathies. [Display omitted] • Human tau (h-tau) driven neurotoxicity induces expression of Glob1 (a Drosophila homologue of human globin). • RNAi mediated restored level of glob1 mitigates h-tau mediated neurotoxicity. • Downregulation of glob1 prevents hyperphosphorylation of tau via GSK-3β/p-Akt and p-JNK pathways. • Downregulation of glob1 activates Nrf2-keap1-ARE cascade to stabilize the level of ROS in h-tau expressing cells. • These two parallel events provide a significant rescue against h-tau mediated neurotoxicity in Drosophila. [ABSTRACT FROM AUTHOR]

• Human tau aggregates migrate trans -cellularly in aging adult Drosophila. • Tau hyperphosphorylation appears to be an important factor for trans -cellular propagation. • Targeted down-regulation of Gsk3β restricts trans -cellular propagation of tau. • This study delivers an easy and rapid in-vivo model for investigation of tau migration pathology. Tauopathies is a class of neurodegenerative disorders which involves the transformation of physiological tau into pathogenic tau. One of the prime causes reported to drive this conversion is tau hyperphosphorylation and the subsequent propagation of pathogenic protein aggregates across the nervous system. Although past attempts have been made to deduce the details of tau propagation, yet not much is known about its mechanism. A better understanding of this aspect of disease pathology can prove to be beneficial for the development of diagnostic and therapeutic approaches. For the first time, we demonstrate that the human tau possesses an intrinsic property to spread trans -cellularly in the fly nervous system irrespective of the tau allele or the neuronal tissue type. Aggregate migration restricted by targeted down-regulation of a specific kinase, elucidates the role of hyper-phosphorylation in its movement. On the contrary to the previous models, our study delivers an easy and rapid in-vivo model for comprehensive examination of tau migration pathology. Henceforth, the developed model would not only be immensely helpful in uncovering the mechanistic in-depths of tau propagation pathology but also aid in modifier and/or drug screening for amelioration of tauopathies. [ABSTRACT FROM AUTHOR]

Functional nanosized two-dimensional clay mineral particles are considered as ideal host materials to manipulate the properties of incorporated organic molecules due to their high cation exchange capacity, layer structure and intercalation properties. The interlayer height of clay layers can be manipulated by simultaneous wetting and drying steps. Here, we have studied the chromatic behaviour of an organic dye generated in-situ from 1,4-di-bis-indolylmethane-benzene in the interlayer space of synthetic saponite (SSA). Initially transparent, self-standing organo-clay hybrid films become red upon heating due to aerobic oxidation suggesting in-situ generation of organic dye and increases the planarity of the intercalated organic molecules. Upon swelling the same hybrid film becomes yellow, due to the partial disturbance in the planarity of generated dye via C-C bond rotation. Simultaneous heating and swelling resulted in a reversible colour transition (clearly visible through the naked eye) between red and yellow for at least 30 cycles. This kind of system may have potential applications as a colorimetric sensor and in the field of optics (optical switching and optical memory etc). Image 1 • Synthesis of tetraindolyl derivative. • Preparation of clay mineral-tetraindolyl hybrid self-standing film. • Colour switching of hybrid film due to the change in gallery height of clay. • Colour switching was reversible with a very good stability. • Such colour switching is suitable for colorimetric sensor, optical switching, optical memory etc. [ABSTRACT FROM AUTHOR]

Polyglutamine/poly(Q) diseases are a group nine hereditary neurodegenerative disorders caused due to abnormally expanded stretches of CAG trinucleotide in functionally distinct genes. All human poly(Q) diseases are characterized by the formation of microscopically discernable poly(Q) positive aggregates, the inclusion bodies. These toxic inclusion bodies are responsible for the impairment of several cellular pathways such as autophagy, transcription, cell death, etc., that culminate in disease manifestation. Although, these diseases remain largely without treatment, extensive research has generated mounting evidences that various events of poly(Q) pathogenesis can be developed as potential drug targets. The present review article briefly discusses the key events of disease pathogenesis, model system-based investigations that support the development of effective therapeutic interventions against pathogenesis of human poly(Q) disorders, and a comprehensive list of pharmacological and bioactive compounds that have been experimentally shown to alleviate poly(Q)-mediated neurotoxicity. Interestingly, due to the common cause of pathogenesis, all poly(Q) diseases share etiology, thus, findings from one disease can be potentially extrapolated to other poly(Q) diseases as well. [Display omitted] • Polyglutamine/poly(Q) disorders are single gene driven autosomal dominant neurodegenerative diseases. • Abnormal expansion of CAG repeats in the mutated gene codes for a pathogenic protein with an expanded poly(Q) stretch. • Proteins with elongated poly(Q) repeats form neurotoxic aggregates and triggers a cascade of pathogenic events. • Impaired proteostasis, mitochondrial function and cellular transcription are key pathogenic events of poly(Q) disorders. • Such pathogenic events have emerged as potential drug target(s) for further development of novel therapeutics. [ABSTRACT FROM AUTHOR]

Traumatic brain injuries are highly recognized as one of the leading causes of mortality and morbidity worldwide. A chronic and debilitating condition by nature, TBI is reportedly affecting the socio-economic well-being of society due to the unavailability of effective prophylaxis. Moreover, TBI is responsible for a myriad of systemic complications such as neurological deficits, gastrointestinal dysfunction, visual impairment, and disturbed circadian rhythm, to name a few. With increasing incidences of TBI-associated disabilities, there is an urgent need for better diagnostics and therapeutic interventions. An array of animal models has been developed to recapitulate pathophysiological conditions of TBI and to elucidate the course of cellular and molecular changes. Although mammalian models are pathophysiologically closer to humans, they decelerate the TBI research due to technical limitations. Therefore, various strategies have been established to model TBI in Drosophila that offer several advantages to study various attributes of TBI and provide a great opportunity for large-scale screening of potential drug molecules. In the present review, we have briefly summarized the fundamentals of brain injuries; contemporary advancements, contributions, and scope of Drosophila in TBI research. [Display omitted] • Traumatic brain injury (TBI) is a prominent health hazard affecting majority of population worldwide. • TBI lacks effective preventive measures, diagnostics and therapeutic interventions. • Modeling TBI is higher organisms imposes various technical and ethical limitations. • Drosophila has emerged as a promising organism to model various aspects of TBI for in-depth investigations. [ABSTRACT FROM AUTHOR]

• Downregulation of dmyc mitigates human-tauV337M mediated neurotoxicity in Drosophila. • Downregulation of dmyc prevents toxic hyperphosphorylation of tauV337M. • Downregulation of dmyc elicits autophagic response in the tau models of Drosophila. Tauopathies such as Alzheimer's disease (AD), Pick's disease (PiD), Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) etc. represent a group of age-related neurodegenerative disorders in which tau protein loses its normal conformation mostly due to hyperphosphorylation and subsequent formation of the aggregates of defined shapes, known as Neurofibrillary Tangles (NFTs). We have demonstrated earlier that reduced dosage of dmyc (Drosophila homolog of human cmyc proto-oncogene) restricts tauWT mediated disease pathogenesis by regulating the phosphorylation status of tau. We demonstrate further that the downregulation of dmyc also alleviates the mutant human-tau (tauV337M) mediated neurotoxicity in Drosophila by improving disease defects. Moreover, tissue-specific downregulation of dmyc also induces cellular autophagy which facilitates the disposal of misfolded proteins via lysosome-mediated proteostasis. Our findings demonstrate the capability of dmyc in the suppression of different forms of human tauopathies in Drosophila disease models. Interestingly, due to the conserved characteristics of dmyc/cmyc across the animal kingdom, our study strengthens the possibility of utilizing this gene as an effective drug target against tauopathies. [ABSTRACT FROM AUTHOR]

Abstract: Plasma enhanced chemical vapor deposition (PECVD) technique using pulsed-DC power supply was used to fabricate diamond like carbon (DLC) films at deposition rates as high as 110 nm/min. The DLC films deposited by pulsed-DC and DC based power supplies under different gas flow ratios were studied for their suitability as dielectric layer coatings in plasma display panels (PDPs). The effect of deposition parameters on the properties of the DLC films were studied using Fourier transform infra-red spectroscopy (FTIR) and spectroscopic ellipsometry (SE). FTIR reveals that higher hydrogen dilution in gas mixture leads to higher sp 3 content. SE studies in wide spectral range were analyzed using Tauc-Lorentz model dielectric function. A rise in the extracted refractive index was seen on increasing the H2 content in the feed gas, thus resulting in optically denser films. Secondary electron emission coefficient (γ) was measured in the films deposited by the DC and pulsed-DC based PECVD. Firing voltage in the DLC samples was found to have very low variation in the operating pressure range used in commercial PDPs, suggesting possibility of enhanced long term reliability of DLC coatings in future PDP applications. [Copyright &y& Elsevier]