Protein Structure Prediction: The Next Generation

Over the last 10-15 years a general understanding of the chemical reaction of protein folding has emerged from statistical mechanics. The lessons learned from protein folding kinetics based on energy landscape ideas have benefited protein structure prediction, in particular the development of coarse grained models. We survey results from blind structure prediction. We explore how second generation prediction energy functions can be developed by introducing information from an ensemble of previously simulated structures. This procedure relies on the assumption of a funnelled energy landscape keeping with the principle of minimal frustration. First generation simulated structures provide an improved input for associative memory energy functions in comparison to the experimental protein structures chosen on the basis of sequence alignment

Re-presenting the Paralympics: (contested) philosophies, production practices and the hypervisibility of disability

Studies that have engaged para-sport broadcasting, particularly through a narrative lens, have almost exclusively relied on textual and/or content analysis of the Paralympic Games as the source of cultural critique. We know far less about the decisions taken inside Paralympic broadcasters that have led to such representations. In this study – based on interviews with senior production and promotion staff at the UK’s Paralympic broadcaster, Channel 4 – we provide the first detailed examination of mediated para-sport from this vantage point. We explore the use of promotional devices such as athletes’ backstories – the “Hollywood treatment” – to both hook audiences and serve as a vehicle for achieving its social enterprise mandate to change public attitudes toward disability. In so doing, we reveal myriad tensions that coalesce around representing the Paralympics; with respect to the efforts made to balance the competing goals of key stakeholders and a stated desire to make the Paralympics both a commercial and socially progressive success

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

Gulf of Mexico Regional Collaborative Final Report

This report presents the results of the Gulf of Mexico Regional Collaborative (GoMRC), a year-long project funded by NASA. The GoMRC project was organized around end user outreach activities, a science applications team, and a team for information technology (IT) development. Key outcomes are summarized below for each of these areas. End User Outreach Successfully engaged federal and state end users in project planning and feedback With end user input, defined needs and system functional requirements Conducted demonstration to End User Advisory Committee on July 9, 2007 and presented at Gulf of Mexico Alliance (GOMA) meeting of Habitat Identification committee Conducted significant engagement of other end user groups, such as the National Estuary Programs (NEP), in the Fall of 2007 Established partnership with SERVIR and Harmful Algal Blooms Observing System (HABSOS) programs and initiated plan to extend HABs monitoring and prediction capabilities to the southern Gulf. Established a science and technology working group with Mexican institutions centered in the State of Veracruz. Key team members include the Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), the Ecological Institute (INECOL) a unit of the National Council for science and technology (CONACYT), the Veracruz Aquarium (NOAA’s first international Coastal Ecology Learning Center) and the State of Veracruz. The Mexican Navy (critical to coastal studies in the Southern Gulf) and other national and regional entities have also been engaged. Training on use of SERVIR portal planned for Fall 2007 in Veracruz, Mexico Science Applications Worked with regional scientists to produce conceptual models of submerged aquatic vegetation (SAV) ecosystems Built a logical framework and tool for ontological modeling of SAV and HABs Created online guidance for SAV restoration planning Created model runs which link potential future land use trends, runoff and SAV viability Analyzed SAV cover change at five other bays in the Gulf of Mexico to demonstrate extensibility of the analytical tools Initiated development of a conceptual model for understanding the causes and effects of HABs in the Gulf of Mexico IT Tool Development Established a website with the GoMRC web-based tools at www.gomrc.org Completed development of an ArcGIS-based decision support tool for SAV restoration prioritization decisions, and demonstrated its use in Mobile Bay Developed a web-based application, called Conceptual Model Explorer (CME), that enables non-GIS users to employ the prioritization model for SAV restoration Created CME tool enabling scientists to view existing, and create new, ecosystem conceptual models which can be used to document cause-effect relationships within coastal ecosystems, and offer guidance on management solutions. Adapted the science-driven advanced web search engine, Noesis, to focus on an initial set of coastal and marine resource issues, including SAV and HABs Incorporated map visualization tools with initial data layers related to coastal wetlands and SAV

The Carnegie Supernova Project: First Near-Infrared Hubble Diagram to z~0.7

The Carnegie Supernova Project (CSP) is designed to measure the luminosity distance for Type Ia supernovae (SNe Ia) as a function of redshift, and to set observational constraints on the dark energy contribution to the total energy content of the Universe. The CSP differs from other projects to date in its goal of providing an I-band {rest-frame} Hubble diagram. Here we present the first results from near-infrared (NIR) observations obtained using the Magellan Baade telescope for SNe Ia with 0.1 < z < 0.7. We combine these results with those from the low-redshift CSP at z <0.1 (Folatelli et al. 2009). We present light curves and an I-band Hubble diagram for this first sample of 35 SNe Ia and we compare these data to 21 new SNe Ia at low redshift. These data support the conclusion that the expansion of the Universe is accelerating. When combined with independent results from baryon acoustic oscillations (Eisenstein et al. 2005), these data yield Omega_m = 0.27 +/- 0.0 (statistical), and Omega_DE = 0.76 +/- 0.13 (statistical) +/- 0.09 (systematic), for the matter and dark energy densities, respectively. If we parameterize the data in terms of an equation of state, w, assume a flat geometry, and combine with baryon acoustic oscillations, we find that w = -1.05 +/- 0.13 (statistical) +/- 0.09 (systematic). The largest source of systematic uncertainty on w arises from uncertainties in the photometric calibration, signaling the importance of securing more accurate photometric calibrations for future supernova cosmology programs. Finally, we conclude that either the dust affecting the luminosities of SNe Ia has a different extinction law (R_V = 1.8) than that in the Milky Way (where R_V = 3.1), or that there is an additional intrinsic color term with luminosity for SNe Ia independent of the decline rate.Comment: 44 pages, 23 figures, 9 tables; Accepted for publication in the Astrophysical Journa

Burmese pythons in Florida: A synthesis of biology, impacts, and management tools

Burmese pythons (Python molurus bivittatus) are native to southeastern Asia, however, there is an established invasive population inhabiting much of southern Florida throughout the Greater Everglades Ecosystem. Pythons have severely impacted native species and ecosystems in Florida and represent one of the most intractable invasive-species management issues across the globe. The difficulty stems from a unique combination of inaccessible habitat and the cryptic and resilient nature of pythons that thrive in the subtropical environment of southern Florida, rendering them extremely challenging to detect. Here we provide a comprehensive review and synthesis of the science relevant to managing invasive Burmese pythons. We describe existing control tools and review challenges to productive research, identifying key knowledge gaps that would improve future research and decision making for python control. (119 pp

Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

Cultural value orientations, internalized homophobia, and accommodation in romantic relationships

In the present study, we examined the impact of cultural value orientations (i.e., the personally oriented value of individualism, and the socially oriented values of collectivism, familism, romanticism, and spiritualism) on accommodation (i.e., voice and loyalty, rather than exit and neglect, responses to partners' anger or criticism) in heterosexual and gay relationships; and we examined the impact of internalized homophobia (i.e., attitudes toward self, other, and disclosure) on accommodation specifically in gay relationships. A total of 262 heterosexuals (102 men and 162 women) and 857 gays (474 men and 383 women) participated in the present study. Consistent with hypotheses, among heterosexuals and gays, socially oriented values were significantly and positively related to accommodation (whereas the personally oriented value of individualism was unrelated to accommodation); and among gays in particular, internalized homophobia was significantly and negatively related to accommodation. Implications for the study of heterosexual and gay relationships are discussed. © 2005 by The Haworth Press, Inc. All rights reserved

Quantitative Evidence for the Effects of Multiple Drivers on Continental-Scale Amphibian Declines

Since amphibian declines were first proposed as a global phenomenon over a quarter century ago, the conservation community has made little progress in halting or reversing these trends. The early search for a “smoking gun” was replaced with the expectation that declines are caused by multiple drivers. While field observations and experiments have identified factors leading to increased local extinction risk, evidence for effects of these drivers is lacking at large spatial scales. Here, we use observations of 389 time-series of 83 species and complexes from 61 study areas across North America to test the effects of 4 of the major hypothesized drivers of declines. While we find that local amphibian populations are being lost from metapopulations at an average rate of 3.79% per year, these declines are not related to any particular threat at the continental scale; likewise the effect of each stressor is variable at regional scales. This result - that exposure to threats varies spatially, and populations vary in their response - provides little generality in the development of conservation strategies. Greater emphasis on local solutions to this globally shared phenomenon is needed

Quantitative Evidence for the Effects of Multiple Drivers on Continental-Scale Amphibian Declines

Since amphibian declines were first proposed as a global phenomenon over a quarter century ago, the conservation community has made little progress in halting or reversing these trends. The early search for a “smoking gun” was replaced with the expectation that declines are caused by multiple drivers. While field observations and experiments have identified factors leading to increased local extinction risk, evidence for effects of these drivers is lacking at large spatial scales. Here, we use observations of 389 time-series of 83 species and complexes from 61 study areas across North America to test the effects of 4 of the major hypothesized drivers of declines. While we find that local amphibian populations are being lost from metapopulations at an average rate of 3.79% per year, these declines are not related to any particular threat at the continental scale; likewise the effect of each stressor is variable at regional scales. This result - that exposure to threats varies spatially, and populations vary in their response - provides little generality in the development of conservation strategies. Greater emphasis on local solutions to this globally shared phenomenon is needed