Rapid optical variability of TeV blazars

In this first systematic attempt to characterise the intranight optical variability (INOV) of TeV detected blazars, we have monitored a well defined set of 9 TeV blazars on total 26 nights during 2004-2010. In this R (or V)-band monitoring programme only one blazar was monitored per night for a minimum duration of 4 hours. Using the CCD, an INOV detection threshold of ~ 1-2 % was achieved in the densely sampled DLCs. We have further expanded the sample by including another 13 TeV blazars from literature. This enlarged sample of 22 TeV blazars, monitored on a total of 116 nights (including 55 nights newly reported here), has enabled us to arrive at the first estimate of the INOV duty cycle of TeV detected blazars. Applying the C-test, the INOV DC is found to be 59 %, which decreases to 47 % if only INOV fractional amplitudes above 3 % are considered. These observations also permit, for the first time, a comparison of the INOV characteristics of the two major subclasses of TeV detected BL Lacs, namely LBLs and HBLs, for which we find the INOV DCs to be ~ 63 % and ~ 38 %, respectively. This demonstrates that the INOV differential between LBLs and HBLs persists even when only their TeV detected subsets are considered. Despite dense sampling, the intranight light curves of the 22 TeV blazars have not revealed even a single feature on time scale substantially shorter than 1 hour, even though the inner jets of TeV blazars are believed to have exceptionally large bulk Lorentz factors (and correspondingly stronger time compression). An intriguing feature, clearly detected in the light curve of the HBL J1555+1111, is a 4 per cent `dip' on a 1 hour timescale. This unique feature could have arisen from absorption in a dusty gas cloud, occulting a superluminally moving optical knot in the parsec scale jet of this relatively luminous BL Lacs object.Comment: 39 pages, 3 figures, accepted for publication in MNRA

Multiwavelength Intraday Variability of the BL Lac S5 0716+714

We report results from a 1 week multi-wavelength campaign to monitor the BL Lac object S5 0716+714 (on December 9-16, 2009). In the radio bands the source shows rapid (~ (0.5-1.5) day) intra-day variability with peak amplitudes of up to ~ 10 %. The variability at 2.8 cm leads by about 1 day the variability at 6 cm and 11 cm. This time lag and more rapid variations suggests an intrinsic contribution to the source's intraday variability at 2.8 cm, while at 6 cm and 11 cm interstellar scintillation (ISS) seems to predominate. Large and quasi-sinusoidal variations of ~ 0.8 mag were detected in the V, R and I-bands. The X-ray data (0.2-10 keV) do not reveal significant variability on a 4 day time scale, favoring reprocessed inverse-Compton over synchrotron radiation in this band. The characteristic variability time scales in radio and optical bands are similar. A quasi-periodic variation (QPO) of 0.9 - 1.1 days in the optical data may be present, but if so it is marginal and limited to 2.2 cycles. Cross-correlations between radio and optical are discussed. The lack of a strong radio-optical correlation indicates different physical causes of variability (ISS at long radio wavelengths, source intrinsic origin in the optical), and is consistent with a high jet opacity and a compact synchrotron component peaking at ~= 100 GHz in an ongoing very prominent flux density outburst. For the campaign period, we construct a quasi-simultaneous spectral energy distribution (SED), including gamma-ray data from the FERMI satellite. We obtain lower limits for the relativistic Doppler-boosting of delta >= 12-26, which for a BL\,Lac type object, is remarkably high.Comment: 16 pages, 15 figures, table 2; Accepted for Publication in MNRA

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Comparative Characterization of Cardiac Development Specific microRNAs: Fetal Regulators for Future

<div><p>MicroRNAs (miRNAs) are small, conserved RNAs known to regulate several biological processes by influencing gene expression in eukaryotes. The implication of miRNAs as another player of regulatory layers during heart development and diseases has recently been explored. However, there is no study which elucidates the profiling of miRNAs during development of heart till date. Very limited miRNAs have been reported to date in cardiac context. In addition, integration of large scale experimental data with computational and comparative approaches remains an unsolved challenge.The present study was designed to identify the microRNAs implicated in heart development using next generation sequencing, bioinformatics and experimental approaches. We sequenced six small RNA libraries prepared from different developmental stages of the heart using chicken as a model system to produce millions of short sequence reads. We detected 353 known and 703 novel miRNAs involved in heart development. Out of total 1056 microRNAs identified, 32.7% of total dataset of known microRNAs displayed differential expression whereas seven well studied microRNAs namely let–7, miR–140, miR–181, miR–30, miR–205, miR–103 and miR–22 were found to be conserved throughout the heart development. The 3’UTR sequences of genes were screened from <i>Gallus gallus</i> genome for potential microRNA targets. The target mRNAs were appeared to be enriched with genes related to cell cycle, apoptosis, signaling pathways, extracellular remodeling, metabolism, chromatin remodeling and transcriptional regulators. Our study presents the first comprehensive overview of microRNA profiling during heart development and prediction of possible cardiac specific targets and has a big potential in future to develop microRNA based therapeutics against cardiac pathologies where fetal gene re-expression is witnessed in adult heart.</p></div

Characterization of microRNA sequences.

<p><b>(A).</b> Identification of microRNAs. Extracted miRNAs and their precursor sequences from all the libraries were compared with the mature chicken miRNAs of miRBase 19.0 allowing zero mismatches. Consequently known and novel microRNAs were obtained from all the stage specific cardiac libraries. Histogram shows the variation in the total number of microRNAs among the libraries. <b>(B).</b> Precursor structure of cardiac specific microRNAs. Precursors of all the known and novel miRNAs were predicted by analysing the typical stem–loop structure in the flanking regions of miRNA genes. Folded structures of precursors of seven conserved microRNAs identified in all six libraries are shown for representation.</p

Expression analysis of conserved microRNAs in all six libraries.

<p><b>(A).</b> Real time PCR studies: the relative abundance/expression of seven conserved microRNAs (3D view). <b>(B).</b> Heat maps of microRNAs expression profiles. Fold change of seven microRNAs that were conserved among the libraries based on deep sequencing data. Box represents the color coding of the heat map with the numbers indicating relative signal intensity.</p

Pathway involvement.

<p><b>(A).</b> KEGG pathway enrichment analysis of cardiac specific target genes identified in Cardiac library (CHL4 as representative candidate library). Only significantly KEGG functional categories (p < 0.05) were depicted according to their p-value. <b>(B).</b> miRNAs-transcription factor interactions. Hypertrophic stimulus leads to activation of multiple signalling pathways which converge on to a common program targeting the activity of cardiac transcription factors and reactivation/modulation of fetal/cardiac gene program in the nucleus which manifest finally as the hypertrophic phenotype. Figure represents that both pro and anti-hypertrophic TFs were targeted by known miRNAs identified in all six libraries.</p

Quality assessment of small RNA reads of cardiac libraries.

<p>Quality of the NGS datasets was checked using quality assessment/quality control (QA/QC) tools. <b>(A).</b> Average quality score per position in all the raw (red) and filtered reads (green): base position is on the horizontal axis, while quality scores are on the vertical axis. <b>(B).</b> Base composition per position in all the sequencing reads (Raw/Filtered) obtained from cardiac libraries. Base positions are on the horizontal axis, while the fraction of each base is on the vertical axis <b>(C).</b> Percentage of GC content in total and filtered reads. Samples are labeled along the horizontal axis and the GC percentage is quantified on the vertical axis.</p