The astrophysics of nanohertz gravitational waves

Pulsar timing array (PTA) collaborations in North America, Australia, and Europe, have been exploiting the exquisite timing precision of millisecond pulsars over decades of observations to search for correlated timing deviations induced by gravitational waves (GWs). PTAs are sensitive to the frequency band ranging just below 1 nanohertz to a few tens of microhertz. The discovery space of this band is potentially rich with populations of inspiraling supermassive black hole binaries, decaying cosmic string networks, relic post-inflation GWs, and even non-GW imprints of axionic dark matter. This article aims to provide an understanding of the exciting open science questions in cosmology, galaxy evolution, and fundamental physics that will be addressed by the detection and study of GWs through PTAs. The focus of the article is on providing an understanding of the mechanisms by which PTAs can address specific questions in these fields, and to outline some of the subtleties and difficulties in each case. The material included is weighted most heavily toward the questions which we expect will be answered in the near-term with PTAs; however, we have made efforts to include most currently anticipated applications of nanohertz GWs

A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression

Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis

Functional Maps of Protein Complexes from Quantitative Genetic Interaction Data

Recently, a number of advanced screening technologies have allowed for the comprehensive quantification of aggravating and alleviating genetic interactions among gene pairs. In parallel, TAP-MS studies (tandem affinity purification followed by mass spectroscopy) have been successful at identifying physical protein interactions that can indicate proteins participating in the same molecular complex. Here, we propose a method for the joint learning of protein complexes and their functional relationships by integration of quantitative genetic interactions and TAP-MS data. Using 3 independent benchmark datasets, we demonstrate that this method is >50% more accurate at identifying functionally related protein pairs than previous approaches. Application to genes involved in yeast chromosome organization identifies a functional map of 91 multimeric complexes, a number of which are novel or have been substantially expanded by addition of new subunits. Interestingly, we find that complexes that are enriched for aggravating genetic interactions (i.e., synthetic lethality) are more likely to contain essential genes, linking each of these interactions to an underlying mechanism. These results demonstrate the importance of both large-scale genetic and physical interaction data in mapping pathway architecture and function

Rotational superradiant scattering in a vortex flow

When an incident wave scatters off of an obstacle, it is partially reflected and partially transmitted. In theory, if the obstacle is rotating, waves can be amplified in the process, extracting energy from the scatterer. Here we describe in detail the first laboratory detection of this phenomenon, known as superradiance 1, 2, 3, 4. We observed that waves propagating on the surface of water can be amplified after being scattered by a draining vortex. The maximum amplification measured was 14% ± 8%, obtained for 3.70 Hz waves, in a 6.25-cm-deep fluid, consistent with the superradiant scattering caused by rapid rotation. We expect our experimental findings to be relevant to black-hole physics, since shallow water waves scattering on a draining fluid constitute an analogue of a black hole 5, 6, 7, 8, 9, 10, as well as to hydrodynamics, due to the close relation to over-reflection instabilities 11, 12, 13

Predicting Quantitative Genetic Interactions by Means of Sequential Matrix Approximation

Despite the emerging experimental techniques for perturbing multiple genes and measuring their quantitative phenotypic effects, genetic interactions have remained extremely difficult to predict on a large scale. Using a recent high-resolution screen of genetic interactions in yeast as a case study, we investigated whether the extraction of pertinent information encoded in the quantitative phenotypic measurements could be improved by computational means. By taking advantage of the observation that most gene pairs in the genetic interaction screens have no significant interactions with each other, we developed a sequential approximation procedure which ranks the mutation pairs in order of evidence for a genetic interaction. The sequential approximations can efficiently remove background variation in the double-mutation screens and give increasingly accurate estimates of the single-mutant fitness measurements. Interestingly, these estimates not only provide predictions for genetic interactions which are consistent with those obtained using the measured fitness, but they can even significantly improve the accuracy with which one can distinguish functionally-related gene pairs from the non-interacting pairs. The computational approach, in general, enables an efficient exploration and classification of genetic interactions in other studies and systems as well

Rationally Designed Turn Promoting Mutation in the Amyloid-β Peptide Sequence Stabilizes Oligomers in Solution

Enhanced production of a 42-residue beta amyloid peptide (Aβ42) in affected parts of the brain has been suggested to be the main causative factor for the development of Alzheimer's Disease (AD). The severity of the disease depends not only on the amount of the peptide but also its conformational transition leading to the formation of oligomeric amyloid-derived diffusible ligands (ADDLs) in the brain of AD patients. Despite being significant to the understanding of AD mechanism, no atomic-resolution structures are available for these species due to the evanescent nature of ADDLs that hinders most structural biophysical investigations. Based on our molecular modeling and computational studies, we have designed Met35Nle and G37p mutations in the Aβ42 peptide (Aβ42Nle35p37) that appear to organize Aβ42 into stable oligomers. 2D NMR on the Aβ42Nle35p37 peptide revealed the occurrence of two β-turns in the V24-N27 and V36-V39 stretches that could be the possible cause for the oligomer stability. We did not observe corresponding NOEs for the V24-N27 turn in the Aβ21–43Nle35p37 fragment suggesting the need for the longer length amyloid peptide to form the stable oligomer promoting conformation. Because of the presence of two turns in the mutant peptide which were absent in solid state NMR structures for the fibrils, we propose, fibril formation might be hindered. The biophysical information obtained in this work could aid in the development of structural models for toxic oligomer formation that could facilitate the development of therapeutic approaches to AD

Congenic Strain Analysis Reveals Genes That Are Rapidly Evolving Components of a Prezygotic Isolation Mechanism Mediating Incipient Reinforcement

Two decades ago, we developed a congenic strain of Mus musculus, called b-congenic, by replacing the androgen-binding protein Abpa27a allele in the C3H/HeJ genome with the Abpa27b allele from DBA/2J. We and other researchers used this b-congenic strain and its C3H counterpart, the a-congenic strain, to test the hypothesis that, given the choice between signals from two strains with different a27 alleles on the same genetic background, test subjects would prefer the homosubspecific one. It was our purpose in undertaking this study to characterize the segment transferred from DBA to the C3H background in producing the b-congenic strain on which a role for ABPA27 in behavior has been predicated. We determined the size of the chromosome 7 segment transferred from DBA and the genes it contains that might influence preference. We found that the “functional" DBA segment is about 1% the size of the mouse haploid genome and contains at least 29 genes expressed in salivary glands, however, only three of these encode proteins identified in the mouse salivary proteome. At least two of the three genes Abpa27, Abpbg26 and Abpbg27 encoding the subunits of androgen-binding protein ABP dimers evolved under positive selection and the third one may have also. In the sense that they are subunits of the same two functional entities, the ABP dimers, we propose that their evolutionary histories might not be independent of each other

The status and challenge of global fire modelling

This is the final version of the article. Available from European Geosciences Union / Copernicus Publications via the DOI in this record.The discussion paper version of this article was published in Biogeosciences Discussions on 25 January 2016 and is in ORE at http://hdl.handle.net/10871/34451Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, using either well-founded empirical relationships or process-based models with good predictive skill. While a large variety of models exist today, it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project (FireMIP), an international initiative to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we review how fires have been represented in fire-enabled dynamic global vegetation models (DGVMs) and give an overview of the current state of the art in fire-regime modelling. We indicate which challenges still remain in global fire modelling and stress the need for a comprehensive model evaluation and outline what lessons may be learned from FireMIP.Stijn Hantson and Almut Arneth acknowledge support by the EU FP7 projects BACCHUS (grant agreement no. 603445) and LUC4C (grant agreement no. 603542). This work was supported, in part, by the German Federal Ministry of Education and Research (BMBF), through the Helmholtz Association and its research programme ATMO, and the HGF Impulse and Networking fund. The MC-FIRE model development was supported by the global change research programmes of the Biological Resources Division of the US Geological Survey (CA 12681901,112-), the US Department of Energy (LWT-6212306509), the US Forest Service (PNW96–5I0 9 -2-CA), and funds from the Joint Fire Science Program. I. Colin Prentice is supported by the AXA Research Fund under the Chair Programme in Biosphere and Climate Impacts, part of the Imperial College initiative Grand Challenges in Ecosystems and the Environment. Fang Li was funded by the National Natural Science Foundation (grant agreement no. 41475099 and no. 2010CB951801). Jed O. Kaplan was supported by the European Research Council (COEVOLVE 313797). Sam S. Rabin was funded by the National Science Foundation Graduate Research Fellowship, as well as by the Carbon Mitigation Initiative. Allan Spessa acknowledges funding support provided by the Open University Research Investment Fellowship scheme. FireMIP is a non-funded community initiative and participation is open to all. For more information, contact Stijn Hantson ([email protected])

The status and challenge of global fire modelling

This is the discussion paper version of the article. The final published version was published in Biogeosciences Vol. 13 (1), pp. 3359-3375 and is in ORE at http://hdl.handle.net/10871/22886Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, either using well-founded empirical relationships or process-based models with good predictive skill. A large variety of models exist today and it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project - FireMIP, an international project to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we summarise the current state-of-the-art in fire regime modelling and model evaluation, and outline what lessons may be learned from FireMIP.Stijn Hantson and Almut Arneth acknowledge support by the EU FP7 projects BACCHUS (grant agreement no. 603445) and LUC4C (grant agreement no. 603542). This work was supported, in part, by the German Federal Ministry of Education and Research (BMBF), through the Helmholtz Association and its research programme ATMO, and the HGF Impulse and Networking fund. The MC-FIRE model development was supported by the global change research programmes of the Biological Resources Division of the US Geological Survey (CA 12681901,112-), the US Department of Energy (LWT6212306509), the US Forest Service (PNW96–5I0 9 -2-CA), and funds from the Joint Fire Science Program. I. Colin Prentice is supported by the AXA Research Fund under the Chair Programme in Biosphere and Climate Impacts, part of the Imperial College initiative Grand Challenges in Ecosystems and the Environment. Fang Li was funded by the National Natural Science Foundation (grant agreement no. 41475099 and no. 2010CB951801). Jed O. Kaplan was supported by the European Research Council (COEVOLVE 313797). Sam S. Rabin was funded by the National Science Foundation Graduate Research Fellowship, as well as by the Carbon Mitigation Initiative. Allan Spessa acknowledges funding support provided by the Open University Research Investment Fellowship scheme. FireMIP is a non-funded community initiative and participation is open to all

Maximal Extraction of Biological Information from Genetic Interaction Data

Targeted genetic perturbation is a powerful tool for inferring gene function in model organisms. Functional relationships between genes can be inferred by observing the effects of multiple genetic perturbations in a single strain. The study of these relationships, generally referred to as genetic interactions, is a classic technique for ordering genes in pathways, thereby revealing genetic organization and gene-to-gene information flow. Genetic interaction screens are now being carried out in high-throughput experiments involving tens or hundreds of genes. These data sets have the potential to reveal genetic organization on a large scale, and require computational techniques that best reveal this organization. In this paper, we use a complexity metric based in information theory to determine the maximally informative network given a set of genetic interaction data. We find that networks with high complexity scores yield the most biological information in terms of (i) specific associations between genes and biological functions, and (ii) mapping modules of co-functional genes. This information-based approach is an automated, unsupervised classification of the biological rules underlying observed genetic interactions. It might have particular potential in genetic studies in which interactions are complex and prior gene annotation data are sparse