Computational Study of Evolutionary Selection Pressure on Rainbow Trout Estrogen Receptors

Molecular dynamics simulations were used to determine the binding affinities between the hormone 17-estradiol (E2) and different estrogen receptor (ER) isoforms in the rainbow trout, Oncorhynchus mykiss. Previous phylogenetic analysis indicates that a whole genome duplication prior to the divergence of ray-finned fish led to two distinct ER isoforms, ER and ER, and the recent whole genome duplication in the ancestral salmonid created two ER isoforms, ER and ER. The objective of our computational studies is to provide insight into the underlying evolutionary pressures on these isoforms. For the ER subtype our results show that E2 binds preferentially to ER over ER. Tests of lineage specific N/S ratios indicate that the ligand binding domain of the ER gene is evolving under relaxed selection relative to all other ER genes. Comparison with the highly conserved DNA binding domain suggests that ER may be undergoing neofunctionalization possibly by binding to another ligand. By contrast, both ER and ER bind similarly to E2 and the best fitting model of selection indicates that the ligand binding domain of all ER genes are evolving under the same level of purifying selection, comparable to ER

A multiscale analysis of social-ecological system robustness and vulnerability in Cornwall, UK

Understanding social-ecological system (SES) feedbacks and interactions is crucial to improving societal resilience to growing environmental challenges. Social-ecological systems are usually researched at one of two spatial scales: local placed-based empirical studies or system-scale modelling, with limited efforts to date exploring the merits of combining these two analytical approaches and scales. Here, we take a multiscale interdisciplinary approach to elucidate the social dynamics underpinning cross-sectoral feedbacks and unintended consequences of decision-making that can affect social-ecological system vulnerability unexpectedly. We combined empirical place-based research with the Robustness Framework, a dynamic system level analysis platform, to analyse the characteristics and robustness of a coastal SES in Cornwall, UK. Embedding place-based empirical analysis into a broader institutional framework revealed SES feedbacks and “maladaptations”. We find that decentralisation efforts coupled with government austerity measures amplify second-order (reputational) risks. This prompted temporal policy trade-offs, which increased individual and community vulnerability and reduced social-ecological system robustness, impeding local adaptation to climate change. We identify opportunities to ameliorate these maladaptations by (1) implementing coordination rules that can guide policymakers in instances of conflicting coastal management pressures, and (2) recognising how second-order risks influence decision-making. This work demonstrates the strengths of combining local and regional analyses to assess the robustness of social-ecological systems exposed to environmental changes, such as climate change and sea level rise. Our results show how analysis of the multiscale effects of climate policies, decision-making processes and second-order risks can usefully support local climate change adaptation planning

Corn Residue Use by Livestock in the United States

Corn (Zea mays L.) residue grazing or harvest provides a simple and economical practice to integrate crops and livestock, but limited information is available on how widespread corn residue utilization is practiced by US producers. In 2010, the USDA Economic Research Service surveyed producers from 19 states on corn grain and residue management practices. Total corn residue grazed or harvested was 4.87 million ha. Approximately 4.06 million ha was grazed by 11.7 million livestock (primarily cattle) in 2010. The majority of grazed corn residue occurred in Nebraska (1.91 million ha), Iowa (385,000 ha), South Dakota (361,000 ha), and Kansas (344,000 ha). Average grazing days ranged from 10 to 73 d (mean = 40 d). Corn residue harvests predominantly occurred in the central and northern Corn Belt, with an estimated 2.9 Tg of corn residue harvested across the 19 states. This survey highlights the importance of corn residue for US livestock, particularly in the western Corn Belt

Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling.

International audienceRecent evidence suggests that many malignancies, including breast cancer, are driven by a cellular subcomponent that displays stem cell-like properties. The protein phosphatase and tensin homolog (PTEN) is inactivated in a wide range of human cancers, an alteration that is associated with a poor prognosis. Because PTEN has been reported to play a role in the maintenance of embryonic and tissue-specific stem cells, we investigated the role of the PTEN/Akt pathway in the regulation of normal and malignant mammary stem/progenitor cell populations. We demonstrate that activation of this pathway, via PTEN knockdown, enriches for normal and malignant human mammary stem/progenitor cells in vitro and in vivo. Knockdown of PTEN in normal human mammary epithelial cells enriches for the stem/progenitor cell compartment, generating atypical hyperplastic lesions in humanized NOD/SCID mice. Akt-driven stem/progenitor cell enrichment is mediated by activation of the Wnt/beta-catenin pathway through the phosphorylation of GSK3-beta. In contrast to chemotherapy, the Akt inhibitor perifosine is able to target the tumorigenic cell population in breast tumor xenografts. These studies demonstrate an important role for the PTEN/PI3-K/Akt/beta-catenin pathway in the regulation of normal and malignant stem/progenitor cell populations and suggest that agents that inhibit this pathway are able to effectively target tumorigenic breast cancer cells

Reassessing the origin of Triton

Agnor & Hamilton (2006) demonstrated that the disruption of a binary was an effective mechanism to capture Triton. The subsequent evolution of Triton's post-capture orbit could have proceeded through gravitational tides. The study by Agnor & Hamilton (2006) is repeated in the framework of the Nice model to determine the post-capture orbit of Triton. After capture it is then subjected to tidal evolution. The perturbations from the Sun and the figure of Neptune are included. The perturbations from the Sun acting on Triton cause it to spend a long time in its high-eccentricity phase, usually of the order of 10 Myr, while the typical time to circularise to its current orbit is some 200 Myr. The current orbit of Triton is consistent with an origin through binary capture and tidal evolution, even though the model prefers Triton to be closer to Neptune than it is today. The probability of capturing Triton in this manner is approximately 0.7%. Since the capture of Triton was at most a 50% event -- since only Neptune has one, but Uranus does not -- we deduce that in the primordial trans-Neptunian disc there were 100 binaries with at least one Triton-sized member. Morbidelli et al. (2009) concludes there were some 1000 Triton-sized bodies in the trans-Neptunian proto-planetary disc, so the primordial binary fraction with at least one Triton-sized member is 10%. This value is consistent with theoretical predictions, but at the low end. If Triton was captured at the same time as Neptune's irregular satellites, the far majority of these, including Nereid, would be lost. This suggests either that Triton was captured on an orbit with a small semi-major axis a < 50 R_N (a rare event), or that it was captured before the dynamical instability of the Nice model, or that some other mechanism was at play. The issue of keeping the irregular satellites remains unresolved.Comment: Accepted in Icarus 201

XMM-Newton and Chandra observations of three X-ray faint early-type galaxies

We present XMM-Newton observations of three X-ray under-luminous elliptical galaxies, NGC 3585, NGC 4494 and NGC 5322. All three galaxies have relatively large optical luminosities (log LB=10.35-10.67 solar) but have X-ray luminosities consistent with emission from discrete sources only. In conjunction with a Chandra observation of NGC 3585, we analyse the XMM data and show that the three galaxies are dominated by discrete source emission, but do possess some X-ray emitting gas. The gas is at relatively low temperatures, kT=0.25-0.44 keV. All three galaxies show evidence of recent dynamical disturbance and formation through mergers, including kinematically distinct cores, young stellar ages, and embedded stellar disks. This leads us to conclude that the galaxies formed relatively recently and have yet to build up large X-ray halos. They are likely to be in a developmental phase where the X-ray gas has a very low density, making it undetectable outside the galaxy core. However, if the gas is a product of stellar mass loss, as seems most probable, we would expect to observe supersolar metal abundances. While abundance is not well constrained by the data, we find best fit abundances <0.1 solar for single-temperature models, and it seems unlikely that we could underestimate the metallicity by such a large factor.Comment: Accepted for publication in MNRAS, 12 pages, 8 postscript figure

A Critical Phenylalanine Residue in the Respiratory Syncytial Virus Fusion Protein Cytoplasmic Tail Mediates Assembly of Internal Viral Proteins into Viral Filaments and Particles

Respiratory syncytial virus (RSV) is a single-stranded RNA virus in the Paramyxoviridae family that assembles into filamentous structures at the apical surface of polarized epithelial cells. These filaments contain viral genomic RNA and structural proteins, including the fusion (F) protein, matrix (M) protein, nucleoprotein (N), and phosphoprotein (P), while excluding F-actin. It is known that the F protein cytoplasmic tail (FCT) is necessary for filament formation, but the mechanism by which the FCT mediates assembly into filaments is not clear. We hypothesized that the FCT is necessary for interactions with other viral proteins in order to form filaments. In order to test this idea, we expressed the F protein with cytoplasmic tail (CT) truncations or specific point mutations and determined the abilities of these variant F proteins to form filaments independent of viral infection when coexpressed with M, N, and P. Deletion of the terminal three FCT residues (amino acids Phe-Ser-Asn) or mutation of the Phe residue resulted in a loss of filament formation but did not affect F-protein expression or trafficking to the cell surface. Filament formation could be restored by addition of residues Phe-Ser-Asn to an FCT deletion mutant and was unaffected by mutations to Ser or Asn residues. Second, deletion of residues Phe-Ser-Asn or mutation of the Phe residue resulted in a loss of M, N, and P incorporation into virus-like particles. These data suggest that a C-terminal Phe residue in the FCT mediates assembly through incorporation of internal virion proteins into virus filaments at the cell surface