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The pioneering studies carried out on heat shock-induced synthesis of specific proteins in the early 1970s did not identify any Hsp60 family protein in Drosophila. By the early 1980s, although the members of Hsp60 family of heat shock proteins (Hsp) were identified in a wide range of eukaryotes as homologs of the bacterial GroEL, none was known in Drosophila. The existence of the Hsp60 family protein was serendipitously revealed in Drosophila in my laboratory in 1989. Contrary to the earlier reports that all tissues in flies display the canonical heat shock response, the larval Malpighian tubules (MT) did not show induction of any of the major Hsps but synthesis of a putative Hsp60 family protein was found to be the most abundant in this tissue. A few years later, we identified this MT-specific heat shock-induced protein to indeed be a member of the Hsp60/chaperonin family. The Drosophila genome sequence projects subsequently revealed four putative Hsp60 gene sequences in the D. melanogaster genome. The present historical perspective chronicles contributions from my and other laboratories that unraveled several aspects of intriguing biology of the multiple Hsp60 genes in D. melanogaster, and highlights challenging questions awaiting future studies. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Genetics emerging as a branch of biology at the beginning of the 20th century for studying biological inheritance. Topics include impacted every area of biology leading to the integration of different fields and of biology with other disciplines of natural sciences and humanities; and researchers in nearly all areas of natural sciences and other disciplines like anthropology, history, judiciary, and economics.

The article presents the discussion on creating wider awareness and promoting good research publication ethics. Topics include researchers in India working under greatly varying conditions of infrastructure, funding, depth of research activity and competence; and Academies and the Government of India ensuring enough funds for maintaining high-quality editing and publishing.

The article discusses the issues related to the publication of research output in peer-reviewed journals. Topics include examines it highlights that commercial publishers have largely taken over the journal publication from academic institutions and learned societies, which has hidden research publications behind paywalls, requiring either author/funder or reader to pay hefty article processing and/or open access charges.

Organisms with heterochromatic sex chromosomes need to compensate for differences in dosages of the sex chromosome-linked genes that have somatic functions. In-depth cytological and subsequent biochemical and molecular studies on dosage compensation started with Mary F. Lyon's proposal in early 1960s that the Barr body in female mammalian somatic cells represented one of the randomly inactivated and heterochromatinized X chromosomes. In contrast, Drosophila was soon shown to achieve dosage compensation through hypertranscription of single X in male whose chromatin remains more open. Identification of proteins that remodel chromatin either to cause one of the two X chromosomes in somatic cells of very early female mammalian embryos to become condensed and inactive or to remodel the single X in male Drosophila embryos to a more open state for hypertranscription provided important insights into the underlying cellular epigenetic processes. However, the most striking and unexpected discoveries were the identification of long noncoding RNAs (lncRNAs), X-inactive specific transcript (Xist) in mammals and roX1/2 in Drosophila, which were essential for achieving the contrasting chromatin organizations but leading to similar end result in terms of dosage compensation of X-linked genes in females and males. An overview of the processes of X inactivation or hyperactivation in mammals and Drosophila, respectively, and the roles played by Xist, roX1/2 and other lncRNAs in these events is presented. [ABSTRACT FROM AUTHOR]

Following earlier reports on modulation of poly(Q) toxicity in Drosophila by the developmentally active and stress-inducible noncoding hsrv gene, we investigated possible mediators of this modulation. RNAi-mediated downregulation of the large nuclear hsrv-n transcript, which organizes the nucleoplasmic omega speckles, suppressed the enhancement of poly(Q) toxicity brought about by reduced availability of the heterogeneous nuclear ribonucleoprotein (hnRNP) Hrb87F and of the transcriptional regulator, cAMP response element binding (CREB) binding protein (CBP). Levels of CBP RNA and protein were reciprocally affected by hsrv transcript levels in eye disc cells. Our data suggest that CBP and hnRNPs like Hrb57A and Hrb87F physically interact with each other. In addition, downregulation of hsrv transcripts partially rescued eye damage following compromised proteasome activity, while overexpression of hsrv and/or poly(Q) proteins disrupted the proteasomal activity. Rescue of poly(Q) toxicity by hsrv-RNAi required normal proteasomal function. We suggest that hsrv-RNAi suppresses poly(Q) toxicity by elevating cellular levels of CBP, by enhancing proteasome-mediated clearance of the pathogenic poly(Q) aggregates, and by inhibiting induced apoptosis. The direct and indirect interactions of the hsrv transcripts with a variety of regulatory proteins like hnRNPs, CBP, proteasome, Drosophila inhibitor of apoptosis protein 1 (DIAP1), etc., reinforce the view that the noncoding hsrv RNA functions as a ''hub'' in cellular networks to maintain homeostasis by coordinating the functional availability of crucial cellular regulatory proteins. [ABSTRACT FROM AUTHOR]

The large nucleus limited noncoding hsrω-n RNA of Drosophila melanogaster is known to associate with a variety of heterogeneous nuclear RNA-binding proteins (hnRNPs) and certain other RNA-biiicling proteins to assemble the nucleoplasmic omega speckles. In this article, we show that RNAi-mediated depletion of this noncoding RNA dominantly suppresses apoptosis, in eye and other imaginal discs, triggered by induced expression of Rpr, Grim, or caspases (initiator as well as effector), all of which are key regulators/effectors of the canonical caspase-mediated cell death pathway. We also show, for the first time, a genetic interaction between the noncoding hsrw transcripts and the c-Jun N-terminal kinase (JNK) signaling pathway since downregulation of hsrw transcripts suppressed JNK activation. In addition, hsrω- RNAi also augmented the levels of Drosophila Inhibitor of Apoptosis Protein 1 (DIAP1) when apoptosis was activated. Suppression of induced cell death following depletion of hsrw transcripts was abrogated when the DIAPJ-RNAi transgene was coexpressed. Our results suggest that the hsrto transcripts regulate cellular levels of DIAP1 via the hnRNP Hrb57A, which physically interacts with DIAP1, and any alteration in levels of the hsrw transcripts in eye disc cells enhances association between these two proteins. Our studies thus reveal a novel regulatory role of the hsrw noncoding RNA on the apoptotic cell death cascade through multiple paths. These observations add to the diversity of regulatory functions that the large noncoding RNAs carry out in the cells' life. [ABSTRACT FROM AUTHOR]

The author discusses various problems faced by researchers in India in achieving excellence in the field of bio-medical research. The author says that there is a huge work force for carrying out research at medical colleges and institutions in India, but very few of them are able to work on well-equipped infrastructure, resulting in poor quality of research. The author says that good performance in medical research can be achieved through commitment for research and innovation.

The article discusses various reports published within the issue, including one on the function of stress proteins/molecular chaperones in aging and degenerative diseases from the perspective of overload of damaged proteins in cells and another on the aspects of stress responses regulation in pro-and eukaryotes.

We exploited the high Ras activity induced differentiation of supernumerary R7 cells in Drosophila eyes to examine if hsrω lncRNAs influence active Ras signaling. Surprisingly, either down- or up-regulation of hsrω lncRNAs in sev-GAL4>Ras V12 expressing eye discs resulted in complete pupal lethality and substantially greater increase in R7 photoreceptor number at the expense of cone cells. Enhanced nuclear p-MAPK and presence of sev-GAL4 driven RasV12 bound RafRBDFLAG in cells not expressing the sev-GAL4 driver indicated non-cell autonomous spread of Ras signaling when hsrω levels were co-altered. RNA-sequencing revealed that down-and up-regulation of hsrω transcripts in sev-GAL4>Ras V12 expressing eye discs elevated transcripts of positive or negative modulators, respectively, of Ras signaling so that either condition enhances it. Altered hsrω transcript levels in sev-GAL4 > Ras V12 expressing discs also affected sn/sno/sca RNAs and some other RNA processing transcript levels. Post-transcriptional changes due to the disrupted intra-cellular dynamicity of omega speckle associated hnRNPs and other RNA-binding proteins that follow down- or up-regulation of hsrω lncRNAs appear to be responsible for the further elevated Ras signaling. Cell autonomous and non-autonomous enhancement of Ras signaling by lncRNAs like hsrω has implications for cell signaling during high Ras activity commonly associated with some cancers. • Our findings highlight roles of hsrω lncRNAs in conditionally modulating the important Ras signaling pathway. • We provide evidence for cell non-autonomous Ras signaling in Drosophila eye discs. [ABSTRACT FROM AUTHOR]

In this article, the author compares between peer reviewing process in late 1960s and 21st century. He cites an example of his career incident in which he and his supervisor A. S. Mukherjee submitted a long manuscript to a journal, following criticism by several reviewers subjecting the manuscript almost to rejection. He Further mentions that today's scenario presents a different picture in which editor's responsibility is to send reviewer's comments and author's responses.

The author examines the effectiveness of ayurveda for the prevention and treatment of the wide-ranging pathological effects of neurological or neurodegenerative disorders caused by genetic and/or environmental factors. Ayurveda is defined as an ancient holistic way of maintaining a healthy and happy human life. It is asserted that ayurvedic practices and formulations appear promising for better health based on the long history of their usage, as well as the results of some experimental studies.

The article presents author's insights regarding insufficiency in the study of methods used for studying biology. It states that automated machines to provide quantitation is important in biological research. It also mentions the newer approaches developed in fly genetics as an example of modern technology that is not fully understood when applied. The author views that young students and researchers must be trained for the methods and technologies used in a given field.

The article discusses the Drosophila Meeting on the state of fly research held in India in 2014. Topics discussed include utility of Drosophila species in research for experimental verification of evolutionary and ecological theories, training of undergraduates and postgraduate students obtaining fly stocks. Other topics include nomination for the Indian Fly Board comprising S. C. Lakhotia and L. S. Shashidhar.

A letter to the editor is presented regarding the state of biotechnology.

Heat shock induced gene expression and other cellular responses help limit the damage caused by stress and thus facilitate cellular recovery. Cellular damage also triggers apoptotic cell death through several pathways. This paper briefly reviews interactions of the major heat shock proteins with components of the apoptotic pathways. Hsp90, which acts as a chaperone for unstable signal transducers to keep them poised for activation, interacts with RIP and Akt and promotes NF-κB mediated inhibition of apoptosis; in addition it also blocks some steps in the apoptotic pathways. Hsp70 is mostly anti-apoptotic and acts at several levels like inhibition of translocation of Bax into mitochondria, release of cytochrome c from mitochondria, formation of apoptosome and inhibition of activation of initiator caspases. Hsp70 also modulates JNK, NF-κB and Akt signaling pathways in the apoptotic cascade. In contrast, Hsp60 has both anti- and pro-apoptotic roles. Cytosolic Hsp60 prevents translocation of the pro-apoptotic protein Bax into mitochondria and thus promotes cell survival but it also promotes maturation of procaspase-3, essential for caspase mediated cell death. Our recent in vivo studies show that RNAi for the Hsp60D in Drosophila melanogaster prevents induced apoptosis. Hsp27 exerts its anti-apoptotic influence by inhibiting cytochrome c and TNF-mediated cell death. αβ crystallin suppresses caspase-8 and cytochrome c mediated activation of caspase-3. Studies in our laboratory also reveal that absence or reduced levels of the developmentally active as well as stress induced non-coding hsrω transcripts, which are known to sequester diverse hnRNPs and related nuclear RNA-binding proteins, block induced apoptosis in Drosophila. Modulation of the apoptotic pathways by Hsps reflects their roles as "weak links" between various "hubs" in cellular networks. On the other hand, non-coding RNAs, by virtue of their potential to bind with multiple proteins, can act as "hubs" in these networks. In view of the integrative nature of living systems, it is not surprising that stress-induced genes, generally believed to primarily function in cell survival pathways, inhibit or even promote cell death pathways at multiple levels to ensure homeostasis at cell and/or organism level. The heat shock genes obviously do much more than merely help cells survive stress. [ABSTRACT FROM AUTHOR]

Scholarly journals play an important role in maintaining the quality and integrity of research by what they publish. Unethical practices in publishing are leading to an increased number of predatory, dubious and low-quality journals worldwide. It has been reported that the percentage of research articles published in predatory journals is high in India. The University Grants Commission (UGC), New Delhi has published an 'approved list of journals', which has been criticized due to inclusion of many substandard journals. We have developed a protocol with objective criteria for identifying journals that do not follow good publication practices. We studied 1336 journals randomly selected from 5699 in the university source component of the 'UGC-approved list'. We analysed 1009 journals after excluding 327 indexed in Scopus/Web of Science. About 34.5% of the 1009 journals were disqualified under the basic criteria because of incorrect or non-availability of essential information such as address, website details and names of editors; another 52.3% of them provided false information such as incorrect ISSN, false claims about impact factor, claimed indexing in dubious indexing databases or had poor credentials of editors. Our results suggest that over 88% of the non-indexed journals in the university source component of the UGC-approved list, included on the basis of suggestions from different universities, could be of low quality. In view of these results, the current UGC-approved list of journals needs serious re-consideration. New regulations to curtail unethical practices in scientific publishing along with organization of awareness programmes about publication ethics at Indian universities and research institutes are urgently needed. [ABSTRACT FROM AUTHOR]

O-GlcNAcylation is an important post-translational modification of proteins and is known to regulate a number of pathways involved in cellular homeostasis. This involves dynamic and reversible modification of serine/threonine residues of different cellular proteins catalyzed by O-linked N-acetylglucosaminyltransferase and O-linked N-acetylglucosaminidase in an antagonistic manner. We report here that decreasing O-GlcNAcylation enhances the viability of neuronal cells expressing polyglutamine-expanded huntingtin exon 1 protein fragment (mHtt). We further show that O-GlcNAcylation regulates the basal autophagic process and that suppression of O-GlcNAcylation significantly increases autophagic flux by enhancing the fusion of autophagosome with lysosome. This regulation considerably reduces toxic mHtt aggregates in eye imaginal discs and partially restores rhabdomere morphology and vision in a fly model for Huntington disease. This study is significant in unraveling O-GlcNAcylation-dependent regulation of an autophagic process in mediating mHtt toxicity. Therefore, targeting the autophagic process through the suppression of O-GlcNAcylation may prove to be an important therapeutic approach in Huntington disease. [ABSTRACT FROM AUTHOR]

We examined two Ayurvedic Rasayana formulations, claimed to facilitate 'healthy ageing', for their role in neuroprotection in fly models of polyQ (127Q and Huntington's) and Alzheimer's disorders. Our earlier findings showed that dietary supplement of Amalaki Rasayana, a preparation derived from Indian gooseberry fruits, and Rasa-Sindoor, an organo-metallic Bhasma prepared from mercury and sulphur, improves general well-being of fruit flies. Here we show that dietary supplement of either of these formulations during larval period substantially suppressed neurodegeneration in fly models of polyQ and Alzheimer's disorders without any side-effects. Dietary Amalaki Rasayana or Rasa-Sindoor prevented accumulation of inclusion bodies and heat shock proteins, suppressed apoptosis, elevated the levels of heterogeneous nuclear ribonucleoproteins and cAMP response element binding protein and at the same time improved the ubiquitin-proteasomal system for better protein clearance in affected cells. Our studies suggest, the potential of these Ayurvedic formulations in providing a holistic relief from the increasingly common neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Background: Ayurveda represents the traditional medicine system of India. Since mechanistic details of therapy in terms of current biology are not available in Ayurvedic literature, modern scientific studies are necessary to understand its major concepts and procedures. It is necessary to examine effects of the whole Ayurvedic formulations rather than their ''active'' components as is done in most current studies. Methods: We tested two different categories of formulations, a Rasayana (Amalaki Rasayana or AR, an herbal derivative) and a Bhasma (Rasa-Sindoor or RS, an organo-metallic derivative of mercury), for effects on longevity, development, fecundity, stress-tolerance, and heterogeneous nuclear ribonucleoprotein (hnRNP) levels of Drosophila melanogaster using at least 200 larvae or flies for each assay. Results: A 0.5% (weight/volume) supplement of AR or RS affected life-history and other physiological traits in distinct ways. While the size of salivary glands, hnRNP levels in larval tissues, and thermotolerance of larvae/adult flies improved significantly following feeding either of the two formulations, the median life span and starvation resistance improved only with AR. Feeding on AR or RS supplemented food improved fecundity differently. Feeding of larvae and adults with AR increased the fecundity while the same with RS had opposite effect. On the contrary, feeding larvae on normal food and adults on AR supplement had no effect on fecundity but a comparable regime of feeding on RS-supplemented food improved fecundity. RS feeding did not cause heavy metal toxicity. Conclusions: The present study with two Ayurvedic formulations reveals formulation-specific effects on several parameters of the fly's life, which seem to generally agree with their recommended human usages in Ayurvedic practices. Thus, Drosophila, with its very rich genetic tools and well-worked-out developmental pathways promises to be a very good model for examining the cellular and molecular bases of the effects of different Ayurvedic formulations. [ABSTRACT FROM AUTHOR]

The complexity in composition and function of the eukaryotic nucleus is achieved through its organization in specialized nuclear compartments. The Drosophila chromatin remodeling ATPase ISWI plays evolutionarily conserved roles in chromatin organization. Interestingly, ISWI genetically interacts with the hsrv gene, encoding multiple non-coding RNAs (ncRNA) essential, among other functions, for the assembly and organization of the omega speckles. The nucleoplasmic omega speckles play important functions in RNA metabolism, in normal and stressed cells, by regulating availability of hnRNPs and some other RNA processing proteins. Chromatin remodelers, as well as nuclear speckles and their associated ncRNAs, are emerging as important components of gene regulatory networks, although their functional connections have remained poorly defined. Here we provide multiple lines of evidence showing that the hsrv ncRNA interacts in vivo and in vitro with ISWI, regulating its ATPase activity. Remarkably, we found that the organization of nucleoplasmic omega speckles depends on ISWI function. Our findings highlight a novel role for chromatin remodelers in organization of nucleoplasmic compartments, providing the first example of interaction between an ATP-dependent chromatin remodeler and a large ncRNA. [ABSTRACT FROM AUTHOR]

We examined interactions between the 83 kDa heat-shock protein (Hsp83) and hsrω long noncoding RNAs (lncRNAs) in hsrω66Hsp90GFP homozygotes, which almost completely lack hsrω lncRNAs but over-express Hsp83. All +/+; hsrω66Hsp90GFP progeny died before the third instar. Rare Sp/CyO; hsrω66Hsp90GFP reached the third instar stage but phenocopied l(2)gl mutants, becoming progressively bulbous and transparent with enlarged brain and died after prolonged larval life. Additionally, ventral ganglia too were elongated. However, hsrω66Hsp90GFP/TM6B heterozygotes, carrying +/+ or Sp/CyO second chromosomes, developed normally. Total RNA sequencing (+/+, +/+; hsrω66/hsrω66, Sp/CyO; hsrω66/hsrω66, +/+; Hsp90GFP/Hsp90GFP and Sp/CyO; hsrω66Hsp90GFP/hsrω66Hsp90GFP late third instar larvae) revealed similar effects on many genes in hsrω66 and Hsp90GFP homozygotes. Besides additive effect on many of them, numerous additional genes were affected in Sp/CyO; hsrω66Hsp90GFP larvae, with l(2)gl and several genes regulating the central nervous system being highly down-regulated in surviving Sp/CyO; hsrω66Hsp90GFP larvae, but not in hsrω66 or Hsp90GFP single mutants. Hsp83 and several omega speckle-associated hnRNPs were bioinformatically found to potentially bind with these gene promoters and transcripts. Since Hsp83 and hnRNPs are also known to interact, elevated Hsp83 in an altered background of hnRNP distribution and dynamics, due to near absence of hsrω lncRNAs and omega speckles, can severely perturb regulatory circuits with unexpected consequences, including down-regulation of tumour-suppressor genes such as l(2)gl. [ABSTRACT FROM AUTHOR]