C-value paradox: Genesis in misconception that natural selection follows anthropocentric parameters of 'economy' and 'optimum'.

C-value paradox refers to the lack of correlation between biological complexity and the intuitively expected protein-coding genomic information or DNA content. Here I discuss five questions about this paradox: i) Do biologically complex organisms carry more protein-coding genes? ii) Does variable accumulation of selfish/ junk/ parasitic DNA underlie the c-value paradox? iii) Can nucleoskeletal or nucleotypic function of DNA explain the enigma of orders of magnitude high levels of DNA in some 'lower' taxa or in taxonomically related species? iv) Can the newly understood noncoding but functional DNA explain the c-value paradox? and, v) Does natural selection uniformly apply the anthropocentric parameters for 'optimum' and 'economy'? Answers to Q.1-5 are largely negative.

"Confessions of an Ayurveda professor" - A wake up call.

Kishor Patwardhan's 'confession' in this journal [1] has initiated the expected debate, which I hope leads to some good developments for the teaching and practice of Ayurveda. Before, commenting on this issue, I should myself confess that I am neither formally trained in Ayurveda nor practising it. A basic research interest in Ayurvedic biology [2] led me to learn about the "fundamental principles" of Ayurveda and to experimentally examine effects of some Ayurvedic formulations using animal models like Drosophila and mouse at organismic, cellular, and molecular levels.

Cytological Approaches to Visualize Intracellular Dynamics of RNA-Binding Proteins at Active Genes in Drosophila.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a family of RNA-binding proteins that modulate multiple aspects of gene activity and RNA processing, including transcription, splicing, localization, translation, and decay of RNA. Interaction of hnRNPs with RNA is a highly dynamic but regulated process. Poly(ADP-ribose) polymerase (PARP)-dependent PARylation of different hnRNPs is a well-known posttranslational modification that affects their interactions with RNA.

Delayed discovery of Hsp60 and subsequent characterization of moonlighting functions of multiple genes in : a personal historical perspective.

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 . 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 . The existence of the Hsp60 family protein was serendipitously revealed in in my laboratory in 1989.

Elevation of major constitutive heat shock proteins is heat shock factor independent and essential for establishment and growth of Lgl loss and Yorkie gain-mediated tumors in Drosophila.

Cancer cells generally overexpress heat shock proteins (Hsps), the major components of cellular stress response, to overcome and survive the diverse stresses. However, the specific roles of Hsps in initiation and establishment of cancers remain unclear. Using loss of Lgl-mediated epithelial tumorigenesis in Drosophila, we induced tumorigenic somatic clones of different genetic backgrounds to examine the temporal and spatial expression and roles of major heat shock proteins in tumor growth.

Dosage compensation in in the 1960s: a personal historical perspective.

Early genetic studies with revealed similar mutant phenotypes for many X-linked genes, in males with one and in females with two copies of the mutant allele following the XY/XX mode of sex determination. These observations led to evocation of the phenomenon of dosage compensation. By the 1960s, contrasting theories were advanced by H.

Conservation of gene architecture and domains amidst sequence divergence in the lncRNA gene across the genus: an analysis.

The developmentally active and cell-stress responsive locus in carries two exons, one intron, one short translatable open reading frame (ORFω), long stretch of unique tandem repeats and an overlapping near its 30' end. It produces multiple long noncoding RNAs (lncRNAs) using two transcription start and four termination sites. Earlier cytogenetic studies revealed functional conservation of in several species.

Activated Ras/JNK driven Dilp8 in imaginal discs adversely affects organismal homeostasis during early pupal stage in Drosophila, a new checkpoint for development.

Background: Dilp8-mediated inhibition of ecdysone synthesis and pupation in holometabolous insects maintains developmental homeostasis through stringent control of timing and strength of molting signals. We examined reasons for normal pupation but early pupal death observed in certain cases.

Results: Overexpression of activated Ras in developing eye/wing discs inhibited Ptth expression in brain via upregulated JNK signaling mediated Dilp8 secretion from imaginal discs, which inhibited ecdysone synthesis in prothoracic gland after pupariation, leading to death of ~25- to 30-hour-old pupae.

Over-expression of Hsp83 in grossly depleted lncRNA background causes synthetic lethality and phenocopy in .

We examined interactions between the 83 kDa heat-shock protein (Hsp83) and long noncoding RNAs (lncRNAs) in Hsp90GFP homozygotes, which almost completely lack lncRNAs but over-express Hsp83. All +/+; Hsp90GFP progeny died before the third instar. Rare Sp/CyO; hsrω Hsp90GFP 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.

Altered levels of hsromega lncRNAs further enhance Ras signaling during ectopically activated Ras induced R7 differentiation in Drosophila.

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 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 Ras bound RafRBDFLAG in cells not expressing the sev-GAL4 driver indicated non-cell autonomous spread of Ras signaling when hsrω levels were co-altered.

Amalaki Rasayana improved memory and neuronal metabolic activity in AbPP-PS1 mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive loss of memory and cognitive function. The cerebral metabolic rate of glucose oxidation has been shown to be reduced in AD. The present study evaluated efficacy of dietary Amalaki Rasayana (AR), an Ayurvedic formulation used in Indian traditional system, in AbPP-PS1 mouse model of AD in ameliorating memory and neurometabolism, and compared with donepezil, a standard FDA approved drug for AD.

Energetics of Excitatory and Inhibitory Neurotransmission in Aluminum Chloride Model of Alzheimer's Disease: Reversal of Behavioral and Metabolic Deficits by Rasa Sindoor.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder, characterized by progressive loss of cognitive functions and memory. Excessive intake of aluminum chloride in drinking water is associated with amyloid plaques and neurofibrillary tangles in the brain, which are the hallmark of AD. We have evaluated brain energy metabolism in aluminum chloride (AlCl) mouse model of AD.

From Heterochromatin to Long Noncoding RNAs in Drosophila: Expanding the Arena of Gene Function and Regulation.

Recent years have witnessed a remarkable interest in exploring the significance of pervasive noncoding transcripts in diverse eukaryotes. Classical cytogenetic studies using the Drosophila model system unraveled the perplexing attributes and "functions" of the "gene"-poor heterochromatin. Recent molecular studies in the fly model are likewise revealing the very diverse and significant roles played by long noncoding RNAs (lncRNAs) in development, gene regulation, chromatin organization, cell and nuclear architecture, etc.

Ayurvedic promotes improved stress tolerance and thus has anti-aging effects in .

Amalaki Rasayana (AR) is a common Ayurvedic herbal formulation of Phyllanthus emblica fruits and some other ingredients, and is used for general good health and healthy aging. We reported it to improve life history traits and to suppress neurodegeneration as well as induced apoptosis in Drosophila. The present study examines responses of Drosophila reared on AR-supplemented food to crowding, thermal or oxidative stresses.

Azadiradione ameliorates polyglutamine expansion disease in Drosophila by potentiating DNA binding activity of heat shock factor 1.

Aggregation of proteins with the expansion of polyglutamine tracts in the brain underlies progressive genetic neurodegenerative diseases (NDs) like Huntington's disease and spinocerebellar ataxias (SCA). An insensitive cellular proteotoxic stress response to non-native protein oligomers is common in such conditions. Indeed, upregulation of heat shock factor 1 (HSF1) function and its target protein chaperone expression has shown promising results in animal models of NDs.

Divergent actions of long noncoding RNAs on X-chromosome remodelling in mammals and Drosophila achieve the same end result: dosage compensation.

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.

The commonly used eye-specific sev-GAL4 and GMR-GAL4 drivers in Drosophila melanogaster are expressed in tissues other than eyes also.

The binary GAL4-UAS system of conditional gene expression is widely used by Drosophila geneticists to target expression of the desired transgene in tissue of interest. In many studies, a preferred target tissue is the Drosophila eye, for which the sev-GAL4 and GMR-GAL4 drivers are most widely used since they are believed to be expressed exclusively in the developing eye cells. However, several reports have noted lethality following expression of certain transgenes under these GAL4 drivers notwithstanding the fact that eye is not essential for survival of the fly.

Expression of hsrω-RNAi transgene prior to heat shock specifically compromises accumulation of heat shock-induced Hsp70 in Drosophila melanogaster.

A delayed organismic lethality was reported in Drosophila following heat shock when developmentally active and stress-inducible noncoding hsrω-n transcripts were down-regulated during heat shock through hs-GAL4-driven expression of the hsrω-RNAi transgene, despite the characteristic elevation of all heat shock proteins (Hsp), including Hsp70. Here, we show that hsrω-RNAi transgene expression prior to heat shock singularly prevents accumulation of Hsp70 in all larval tissues without affecting transcriptional induction of hsp70 genes and stability of their transcripts. Absence of the stress-induced Hsp70 accumulation was not due to higher levels of Hsc70 in hsrω-RNAi transgene-expressing tissues.

The hnRNP A1 homolog Hrb87F/Hrp36 is important for telomere maintenance in Drosophila melanogaster.

Unlike the telomerase-dependent mammalian telomeres, HeT-A, TART, and TAHRE (HTT) retroposon arrays regulate Drosophila telomere length. Cap prevents telomeric associations (TAs) and telomeric fusions (TFs). Our results suggest important roles of Hrb87F in telomeric HTT array and cap maintenance in Drosophila.

Suppression of induced but not developmental apoptosis in Drosophila by Ayurvedic Amalaki Rasayana and Rasa-Sindoor.

Earlier we showed formulation-specific beneficial effects of dietary supplement of Ayurvedic Amalaki Rasayana (AR, a herbal formulation) and Rasa-Sindoor (RS, a mercury-based organo-metallic formulation) on various biological parameters in Drosophila, parallel to traditional Ayurvedic literature. These formulations also suppressed cell death and pathology in fly models of neurodegeneration. To understand basis of inhibition of apoptosis, we examined effects of AR and RS on induced and developmental apoptosis in Drosophila.

Dynamics of hnRNPs and omega speckles in normal and heat shocked live cell nuclei of Drosophila melanogaster.

The nucleus limited long-noncoding hsrω-n transcripts, hnRNPs, and some other RNA processing proteins organize nucleoplasmic omega speckles in Drosophila. Unlike other nuclear speckles, omega speckles rapidly disappear following cell stress, while hnRNPs and other associated proteins move away from chromosome sites, nucleoplasm, and the disappearing speckles to get uniquely sequestered at hsrω locus. Omega speckles reappear and hnRNPs get redistributed to normal locations during recovery from stress.

Decreased O-linked GlcNAcylation protects from cytotoxicity mediated by huntingtin exon1 protein fragment.

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).