Local Difference Measures between Complex Networks for Dynamical System Model Evaluation

Acknowledgments We thank Reik V. Donner for inspiring suggestions that initialized the work presented herein. Jan H. Feldhoff is credited for providing us with the STARS simulation data and for his contributions to fruitful discussions. Comments by the anonymous reviewers are gratefully acknowledged as they led to substantial improvements of the manuscript.Peer reviewedPublisher PD

Integrative analysis of large scale expression profiles reveals core transcriptional response and coordination between multiple cellular processes in a cyanobacterium

<p>Abstract</p> <p>Background</p> <p>Cyanobacteria are the only known prokaryotes capable of oxygenic photosynthesis. They play significant roles in global biogeochemical cycles and carbon sequestration, and have recently been recognized as potential vehicles for production of renewable biofuels. <it>Synechocystis </it>sp. PCC 6803 has been extensively used as a model organism for cyanobacterial studies. DNA microarray studies in <it>Synechocystis </it>have shown varying degrees of transcriptome reprogramming under altered environmental conditions. However, it is not clear from published work how transcriptome reprogramming affects pre-existing networks of fine-tuned cellular processes.</p> <p>Results</p> <p>We have integrated 163 transcriptome data sets generated in response to numerous environmental and genetic perturbations in <it>Synechocystis</it>. Our analyses show that a large number of genes, defined as the core transcriptional response (CTR), are commonly regulated under most perturbations. The CTR contains nearly 12% of <it>Synechocystis </it>genes found on its chromosome. The majority of genes in the CTR are involved in photosynthesis, translation, energy metabolism and stress protection. Our results indicate that a large number of differentially regulated genes identified in most reported studies in <it>Synechocystis </it>under different perturbations are associated with the general stress response. We also find that a majority of genes in the CTR are coregulated with 25 regulatory genes. Some of these regulatory genes have been implicated in cellular responses to oxidative stress, suggesting that reactive oxygen species are involved in the regulation of the CTR. A Bayesian network, based on the regulation of various KEGG pathways determined from the expression patterns of their associated genes, has revealed new insights into the coordination between different cellular processes.</p> <p>Conclusion</p> <p>We provide here the first integrative analysis of transcriptome data sets generated in a cyanobacterium. This compilation of data sets is a valuable resource to researchers for all cyanobacterial gene expression related queries. Importantly, our analysis provides a global description of transcriptional reprogramming under different perturbations and a basic framework to understand the strategies of cellular adaptations in <it>Synechocystis</it>.</p

A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-19), ACE2, and the immune system: a dichotomy of expectation and reality

The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly defined. The safety of non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, has been openly questioned without any supporting evidence or clarity over dose, duration, or temporality of administration. This has been further conflicted by the initiation of studies to assess the efficacy of ibuprofen in improving outcomes in severe COVID-19 patients. To clarify the scientific reality, a literature search was conducted alongside considerations of the pharmacological properties of ibuprofen in order to construct this narrative review. The literature suggests that double-blind, placebo-controlled study results must be reported and carefully analysed for safety and efficacy in patients with COVID-19 before any recommendations can be made regarding the use of ibuprofen in such patients. Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain. Additionally, in vitro evidence suggests that inhibition of the transcription factor nuclear factor-κB (NF-kB) by ibuprofen may have a role in reducing excess inflammation or cytokine release in COVID-19 patients. Finally, there is no evidence that ibuprofen will aggravate or increase the chance of infection of COVID-19

G-quadruplex structures within the 3' UTR of LINE-1 elements stimulate retrotransposition

Long interspersed nuclear elements (LINEs) are ubiquitous transposable elements in higher eukaryotes that have a significant role in shaping genomes, owing to their abundance. Here we report that guanine-rich sequences in the 3' untranslated regions (UTRs) of hominoid-specific LINE-1 elements are coupled with retrotransposon speciation and contribute to retrotransposition through the formation of G-quadruplex (G4) structures. We demonstrate that stabilization of the G4 motif of a human-specific LINE-1 element by small-molecule ligands stimulates retrotransposition.S.B. is a Wellcome Trust Senior Investigator (grant 099232/z/12/z). The Balasubramanian group is supported by European Research Council Advanced Grant 339778, and receives core (C14303/A17197) and program (C9681/A18618) funding from Cancer Research UK

Impaired health status and invasivc treatment in peripheral arterial disease:A prospective 1-year follow-up study

ObjectiveIt has been argued that health status and quality of life (QOL) should be taken into account in the treatment policy of patients with peripheral arterial disease (PAD). In cardiac patients, it has been shown that poor perceived health status is an independent predictor of mortality and hospitalization. We therefore examined (1) the role of health status, QOL, and clinical indices of disease severity as determinants of invasive treatment in patients with PAD and (2) the effect of invasive treatment on health status and QOL.MethodsAt their first visit, patients completed the RAND 36-item Health Survey and World Health Organization Quality of Life assessment instrument questionnaires to assess health status and QOL, respectively. During the 1-year follow-up period, data concerning hospitalization were derived from the patients’ medical files. Furthermore, patients completed the RAND 36 and the World Health Organization Quality of Life assessment instrument again at 1-year follow-up. The setting was a vascular outpatient clinic of a teaching hospital in Tilburg, The Netherlands; participants were 200 consecutive patients newly diagnosed with intermittent claudication, a common expression of PAD. Diagnosis was based on history, physical examination, treadmill walking distance, and ankle-brachial pressure indices. Main outcome measures were (1) invasive treatment of PAD that took place during the 1-year follow-up, derived from the patients’ medical files, and (2) health status and QOL after 1 year of follow-up.ResultsAfter 1 year of follow-up, 107 patients (53.5%) were event free, whereas 77 patients (38.5%) had been hospitalized for invasive treatment of PAD. Sixteen patients (8%) were hospitalized for other cardiovascular reasons. In a multivariate logistic regression model, age (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.91–0.99; P = .024), pain-free walking distance (OR, 2.74; 95% CI, 1.05–7.17; P = .04), and physical functioning (OR, 4.46; 95% CI, 1.79–11.12; P = .001) were independent predictors of invasive treatment of intermittent claudication. After 1 year of follow-up, patients who were treated invasively experienced a significant improvement in their physical functioning (P = .004), role limitations due to emotional problems (P = .018), and bodily pain (P = .026).ConclusionsPatients with poor self-reported physical functioning, limited walking distance, and a younger age were likely to be treated invasively. The physician’s clinical judgment about when to intervene adequately reflects the patient’s own opinion about his or her health status. Invasive treatment led to a significant improvement in patients’ health status. These findings indicate the effectiveness of the strategy to include patients’ perceived physical functioning into the process of clinical decision-making