Mapping H4K20me3 onto the chromatin landscape of senescent cells indicates a function in control of cell senescence and tumor suppression through preservation of genetic and epigenetic stability

Background: Histone modification H4K20me3 and its methyltransferase SUV420H2 have been implicated in suppression of tumorigenesis. The underlying mechanism is unclear, although H4K20me3 abundance increases during cellular senescence, a stable proliferation arrest and tumor suppressor process, triggered by diverse molecular cues, including activated oncogenes. Here, we investigate the function of H4K20me3 in senescence and tumor suppression. Results: Using immunofluorescence and ChIP-seq we determine the distribution of H4K20me3 in proliferating and senescent human cells. Altered H4K20me3 in senescence is coupled to H4K16ac and DNA methylation changes in senescence. In senescent cells, H4K20me3 is especially enriched at DNA sequences contained within specialized domains of senescence-associated heterochromatin foci (SAHF), as well as specific families of non-genic and genic repeats. Altered H4K20me3 does not correlate strongly with changes in gene expression between proliferating and senescent cells; however, in senescent cells, but not proliferating cells, H4K20me3 enrichment at gene bodies correlates inversely with gene expression, reflecting de novo accumulation of H4K20me3 at repressed genes in senescent cells, including at genes also repressed in proliferating cells. Although elevated SUV420H2 upregulates H4K20me3, this does not accelerate senescence of primary human cells. However, elevated SUV420H2/H4K20me3 reinforces oncogene-induced senescence-associated proliferation arrest and slows tumorigenesis in vivo. Conclusions: These results corroborate a role for chromatin in underpinning the senescence phenotype but do not support a major role for H4K20me3 in initiation of senescence. Rather, we speculate that H4K20me3 plays a role in heterochromatinization and stabilization of the epigenome and genome of pre-malignant, oncogene-expressing senescent cells, thereby suppressing epigenetic and genetic instability and contributing to long-term senescence-mediated tumor suppression

Not Available

Not AvailableBackground In the view of endemic avian influenza H9N2 infection in poultry, its zoonotic potential and emergence of antiviral resistance, two herbal plants, Ocimum sanctum and Acacia arabica, which are easily available throughout various geographical locations in India were taken up to study their antiviral activity against H9N2 virus. We evaluated antiviral efficacy of three different extracts each from leaves of O. sanctum (crude extract, terpenoid and polyphenol) and A. arabica (crude extract, flavonoid and polyphenol) against H9N2 virus using in ovo model. Methods The antiviral efficacy of different leaves extracts was systematically studied in three experimental protocols viz. virucidal (dose-dependent), therapeutic (time-dependent) and prophylactic (dose-dependent) activity employing in ovo model. The maximum non-toxic concentration of each herbal extracts of O. sanctum and A. arabica in the specific pathogen free embryonated chicken eggs was estimated and their antiviral efficacy was determined in terms of reduction in viral titres, measured by Haemagglutination (HA) and real time quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays. Results All the extracts of O. sanctum (crude extract, terpenoid and polyphenol) and A. arabica (crude extract, flavonoid and polyphenol) showed significant virucidal activity, however, crude extractocimum and terpenoidocimum showed highly significant to significant (p < 0.001–0.01) decrease in virus genome copy numbers with lowest dose tested. Similarly, therapeutic effect was observed in all three extracts of O. sanctum in comparison to the virus control, nevertheless, crude extractocimum and terpenoidocimum maintained this effect for longer period of time (up to 72 h post-incubation). None of the leaves extracts of A. arabica had therapeutic effect at 24 and 48 h post-incubation, however, only the crude extractacacia and polyphenolacacia showed delayed therapeutic effect (72 h post-inoculation). Prophylactic potential was observed in polyphenolacacia with highly significant antiviral activity compared to virus control (p < 0.001). Conclusions The crude extract and terpenoid isolated from the leaves of O. sanctum and polyphenol from A. arabica has shown promising antiviral properties against H9N2 virus. Future investigations are necessary to formulate combinations of these compounds for the broader antiviral activity against H9N2 viruses and evaluate them in chickens.Not Availabl

Investigation of Uttarakhand (India) disaster-2013 using weather research and forecasting model

A natural disaster in the form of severe flash floods due to extreme precipitation occurred at Kedarnath (Uttarakhand), India, on 16–17 June 2013 and is being considered as one of the worst disasters in India (Das in J Geol Soc India 82:201, 2013). The catastrophe in the form of flash flood and associated debris flow caused major devastation leading to a high death toll of locals and visiting pilgrims. The very early migration of monsoon trough (MT) towards northern India and its interaction with an incoming western disturbance (WD) formed a transient cloud system that led to extreme precipitation. Using WRF model with triple-nested domain for simulation at finer resolutions, this high-intensity precipitating event is analysed. Interaction of the MT with WD over the foothills of the Himalayas usually causes a break period in the Indian monsoon, but the interaction of MT and WD during this storm event showed different characteristics. Such an association of WD with the MT has been termed as pulsatory extension of the monsoon (PEM) towards Himalayas (Pisharoty and Desai in Indian J Meteorol Geophys 7:333–338, 1956; Mooley in Indian J Meteorol Hydrol Geophys 8:253–260, 1957). The interaction of the WD with the MT exactly over the Uttarakhand region forms an occluded discontinuity between the mid to upper-tropospheric WD frontal system (colder) and the lower-troposphere MT (warm and humid). The precursor of this front caused formation of steep temperature gradient over the Indian region that led to the early advance of MT towards Himalayas. Formation of this strong front develops augmented convective instability, which is further enhanced by orographic lifting, leading to the configuration of this large organized storm causing extreme precipitation over a large spatial region

Genetic estimation of iterated function systems for accurate fractal modeling in pattern recognition tools

3noIn this paper, we describe an algorithm to estimate the parameters of Iterated Function System (IFS) fractal models. We use IFS to model Speech and Electroencephalographic signals and compare the results. The IFS parameters estimation is performed by means of a genetic optimization approach. We show that the estimation algorithm has a very good convergence to the global minimum. This can be successfully exploited by pattern recognition tools. However, the set-up of the genetic algorithm should be properly tuned. In this paper, besides the optimal set-up description, we describe also the best tradeoff between performance and computational complexity. To simplify the optimization problem some constraints are introduced. A comparison with suboptimal algorithms is reported. The performance of IFS modeling of the considered signals are in accordance with known measures of the fractal dimension.partially_openopenCuzzocrea, Alfredo*; Mumolo, Enzo; Grasso, Giorgio MarioCuzzocrea, Alfredo; Mumolo, Enzo; Grasso, Giorgio Mari