Sequencing of \u3ci\u3eAspergillus nidulans\u3c/i\u3e and comparative analysis with \u3ci\u3eA. fumigatus\u3c/i\u3e and \u3ci\u3eA. oryzae\u3c/i\u3e

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso, and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation. Document includes all supplementary information (820 pages). Supplementary files are also attached below as Related files. THERE IS NO SUPPLEMENTARY FILE #7. PDF file size (with supplementary files included) is 10 Mbytes. An optimized version of the ARTICLE ONLY is attached as a Related File and is 1.9 Mbytes

Sequencing of \u3ci\u3eAspergillus nidulans\u3c/i\u3e and comparative analysis with \u3ci\u3eA. fumigatus\u3c/i\u3e and \u3ci\u3eA. oryzae\u3c/i\u3e

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso, and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation. Document includes all supplementary information (820 pages). Supplementary files are also attached below as Related files. THERE IS NO SUPPLEMENTARY FILE #7. PDF file size (with supplementary files included) is 10 Mbytes. An optimized version of the ARTICLE ONLY is attached as a Related File and is 1.9 Mbytes

Observation of electroweak production of two jets in association with an isolated photon and missing transverse momentum, and search for a Higgs boson decaying into invisible particles at 13 TeV with the ATLAS detector

This paper presents the measurement of the electroweak production of two jets in association with a $Z\gamma$ pair with the $Z$ boson decaying into two neutrinos. It also presents the search for invisible or partially invisible decays of a Higgs boson with a mass of 125 GeV produced through vector-boson fusion with a photon in the final state. These results use data from LHC proton-proton collisions at $\sqrt{s}$ = 13 TeV collected with the ATLAS detector corresponding to an integrated luminosity of 139 fb$^{-1}$. The event signature, shared by all benchmark processes considered for measurements and searches, is characterized by a significant amount of unbalanced transverse momentum and a photon in the final state, in addition to a pair of forward jets. For electroweak production of $Z\gamma$ in association with two jets, the background-only hypothesis is rejected with an observed (expected) significance of 5.2 (5.1) standard deviations. The measured fiducial cross-section for this process is 1.31$\pm$0.29 fb. Observed (expected) upper limit of 0.37 (0.34) at 95% confidence level is set on the branching ratio of a 125 GeV Higgs boson to invisible particles, assuming the Standard Model production cross-section. The signature is also interpreted in the context of decays of a Higgs boson to a photon and a dark photon. An observed (expected) 95% CL upper limit on the branching ratio for this decay is set at 0.018 (0.017), assuming the 125 GeV Standard Model Higgs boson production cross-section

Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance

Obesity-induced metabolic disease involves functional integration among several organs via circulating factors, but little is known about crosstalk between liver and visceral adipose tissue (VAT). In obesity, VAT becomes populated with inflammatory adipose tissue macrophages (ATMs). In obese humans, there is a close correlation between adipose tissue inflammation and insulin resistance, and in obese mice, blocking systemic or ATM inflammation improves insulin sensitivity. However, processes that promote pathological adipose tissue inflammation in obesity are incompletely understood. Here we show that obesity in mice stimulates hepatocytes to synthesize and secrete dipeptidyl peptidase 4 (DPP4), which acts with plasma factor Xa to inflame ATMs. Silencing expression of DPP4 in hepatocytes suppresses inflammation of VAT and insulin resistance; however, a similar effect is not seen with the orally administered DPP4 inhibitor sitagliptin. Inflammation and insulin resistance are also suppressed by silencing expression of caveolin-1 or PAR2 in ATMs; these proteins mediate the actions of DPP4 and factor Xa, respectively. Thus, hepatocyte DPP4 promotes VAT inflammation and insulin resistance in obesity, and targeting this pathway may have metabolic benefits that are distinct from those observed with oral DPP4 inhibitors