A meta-analysis of gene expression signatures of blood pressure and hypertension

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%-9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension.Tianxiao Huan, Tõnu Esko, Marjolein J. Peters, Luke C. Pilling, Katharina Schramm, Claudia Schurmann, Brian H. Chen, Chunyu Liu, Roby Joehanes, Andrew D. Johnson, Chen Yao, Sai-xia Ying, Paul Courchesne, Lili Milani, Nalini Raghavachari, Richard Wang, Poching Liu, Eva Reinmaa, Abbas Dehghan, Albert Hofman, André G. Uitterlinden, Dena G. Hernandez, Stefania Bandinelli, Andrew Singleton, David Melzer, Andres Metspalu, Maren Carstensen, Harald Grallert, Christian Herder, Thomas Meitinger, Annette Peters, Michael Roden, Melanie Waldenberger, Marcus Dörr, Stephan B. Felix, Tanja Zeller, International Consortium for Blood Pressure GWAS, ICBP, Ramachandran Vasan, Christopher J. O'Donnell, Peter J. Munson, Xia Yang, Holger Prokisch, Uwe Völker, Joyce B. J. van Meurs, Luigi Ferrucci, Daniel Lev

Efficient Physical Embedding of Topologically Complex Information Processing Networks in Brains and Computer Circuits

Nervous systems are information processing networks that evolved by natural selection, whereas very large scale integrated (VLSI) computer circuits have evolved by commercially driven technology development. Here we follow historic intuition that all physical information processing systems will share key organizational properties, such as modularity, that generally confer adaptivity of function. It has long been observed that modular VLSI circuits demonstrate an isometric scaling relationship between the number of processing elements and the number of connections, known as Rent's rule, which is related to the dimensionality of the circuit's interconnect topology and its logical capacity. We show that human brain structural networks, and the nervous system of the nematode C. elegans, also obey Rent's rule, and exhibit some degree of hierarchical modularity. We further show that the estimated Rent exponent of human brain networks, derived from MRI data, can explain the allometric scaling relations between gray and white matter volumes across a wide range of mammalian species, again suggesting that these principles of nervous system design are highly conserved. For each of these fractal modular networks, the dimensionality of the interconnect topology was greater than the 2 or 3 Euclidean dimensions of the space in which it was embedded. This relatively high complexity entailed extra cost in physical wiring: although all networks were economically or cost-efficiently wired they did not strictly minimize wiring costs. Artificial and biological information processing systems both may evolve to optimize a trade-off between physical cost and topological complexity, resulting in the emergence of homologous principles of economical, fractal and modular design across many different kinds of nervous and computational networks

A Fermi Gamma-Ray Burst Monitor Search for Electromagnetic Signals Coincident with Gravitational-wave Candidates in Advanced LIGO's First Observing Run

We present a search for prompt gamma-ray counterparts to compact binary coalescence gravitational wave (GW) candidates from Advanced LIGO's first observing run (O1). As demonstrated by the multimessenger observations of GW170817/GRB 170817A, electromagnetic and GW observations provide complementary information about the astrophysical source, and in the case of weaker candidates, may strengthen the case for an astrophysical origin. Here we investigate low-significance GW candidates from the O1 compact binary coalescence searches using the Fermi Gamma-Ray Burst Monitor (GBM), leveraging its all sky and broad energy coverage. Candidates are ranked and compared to background to measure the significance. Those with false alarm rates (FARs) of less than 10−5 Hz (about one per day, yielding a total of 81 candidates) are used as the search sample for gamma-ray follow-up. No GW candidates were found to be coincident with gamma-ray transients independently identified by blind searches of the GBM data. In addition, GW candidate event times were followed up by a separate targeted search of GBM data. Among the resulting GBM events, the two with the lowest FARs were the gamma-ray transient GW150914-GBM presented in Connaughton et al. and a solar flare in chance coincidence with a GW candidate

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

Peer reviewe

Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

Peer reviewe

Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

Peer reviewe

Measurement of prompt J/ψ pair production in pp collisions at √s = 7 Tev

Peer reviewe

Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV

Peer reviewe

Measurement of top quark–antiquark pair production in association with a W or Z boson in pp collisions at √s=8 TeV

Peer reviewe