Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

Dinámica del contenido de humedad de pastos y su relación con la ecología del fuego en región chaqueña occidental (Argentina)

El fuego es un evento frecuente en la región chaqueña argentina. El contenido de agua (CH, %) es un factor que define la inflamabilidad de los combustibles vegetales y su dinámica temporal puede ser usada para comprender la ecología del fuego en una región, planificar su uso como prescripto; o como un indicador de riesgo para su prevención. En este trabajo se evaluó la dinámica de CH a través del tiempo en tres sitios ecológicos (≈ modelos de combustible) de la región chaqueña, en muestras con Elionorus muticus como especie dominante (sitio bajo, sabana), Trichloris pluriflora y Pappopphorum pappipherum (sitio media loma, parques) y una especie exótica, Panicum máximum cv Gatton (sitio loma, bosque secundario rolado), respectivamente. El CH fue determinado en forma gravimétrica mensualmente en el bajo en 1992; y cada 10-15 días entre mayo 2008 y octubre 2009 en la media loma y la loma. Los datos fueron analizados en forma gráfica y mediante análisis de la varianza empleando estación climática, especie y tiempo cronológico como factores de clasificación. El CH promedio de las especies a través del tiempo presentó una amplitud estacional marcada, entre 4-5% en invierno-primavera y mayor al 150% en verano-otoño. Las especies nativas presentaron un CH significativamente menor que P. maximum y más bajo que el umbral de extinción teórico (CH=30%) indicando que en la región chaqueña, como en otros ecosistemas, las gramíneas y sus formaciones vegetales son el combustible por donde se propaga el fuego. La dinámica temporal de CH podría ser representada por una sinusoide. La correlación entre CH y la máxima humedad relativa entre fechas de muestreo fue significativa. Ambos resultados sugieren que es factible usar funciones matemáticas conocidas y métodos indirectos para predecir CH y la ‘inflamabilidad’ del combustible en las estaciones climáticas, facilitando la predicción del comportamiento de fuego.Fire is a common event in the Chaco region of Argentina. The fuel moisture content (CH, %) is a factor defining flammability. Its changes throughout time could be used as an index of fire risk, to understand fire ecology, and for planning the use of prescribed fire. We assessed CH dynamics in three ecological sites (≈fuel models): samples with Elionorus muticus as dominant species (lowland, savanna); Trichloris pluriflora y Pappopphorum pappipherum (midland, parkand) and an exotic species Panicum máximum cv Gatton (upland, roller-chopped secondary forest). CH was monitored using the gravimetric method every month in the lowland during 1992; and every 10-15 days from May 2008 to October 2009 in the midland and upland sites. Data were analyzed graphically and with analysis of variance using season, chronological time and species as classification factors. The average CH of the species presented a marked seasonal trend, with a large amplitude, from 4-5% in the winter to above 150 % in summer and fall, respectively. The CH of the native species was significantly lower than P. maximum, and also lower than the extinction threshold (CH = 30 %) suggesting that in the Chaco region, as well as in other ecosystems, grasses are the fuel where fire starts and propagate to other plant communities. Correlation between CH and the maximum air relative humidity observed between sampling dates was significant. The latter fact and the sinusoidal pattern of CH suggest that may be feasible the use of known mathematical functions and indirect methods to predict CH, helping in predict fire behavior throughout the seasons.EEA Santiago del EsteroFil: Kunst, Carlos Roberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santiago del Estero; ArgentinaFil: Ledesma, Roxana Ramona. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santiago del Estero; ArgentinaFil: Bravo, Sandra. Universidad Nacional de Santiago del Estero. Facultad de Ciencias Forestales. Cátedra de Botánica; ArgentinaFil: Defossé, Guillermo E. Centro de Investigación y Extensión Forestal Andino Patagónico; Argentina. Universidad Nacional de la Patagonia San Juan Bosco. Sede Esquel; ArgentinaFil: Godoy, Jose Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santiago del Estero; ArgentinaFil: Navarrete, Victor Del Carmen. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santiago del Estero; ArgentinaFil: Jaime, Napoleon Ar. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santiago del Estero; Argentin

Dinámica del contenido de humedad de pastos y su relación con la ecología del fuego en región chaqueña occidental (Argentina)

El fuego es un evento frecuente en la región chaqueña argentina. El contenido de agua (CH, %) es un factor que define la inflamabilidad de los combustibles vegetales y su dinámica temporal puede ser usada para comprender la ecología del fuego en una región, planificar su uso como prescripto; o como un indicador de riesgo para su prevención. En este trabajo se evaluó la dinámica de CH a través del tiempo en tres sitios ecológicos (≈ modelos de combustible) de la región chaqueña, en muestras con Elionorus muticus como especie dominante (sitio bajo, sabana), Trichloris pluriflora y Pappopphorum pappipherum (sitio media loma, parques) y una especie exótica, Panicum máximum cv Gatton (sitio loma, bosque secundario rolado), respectivamente. El CH fue determinado en forma gravimétrica mensualmente en el bajo en 1992; y cada 10-15 días entre mayo 2008 y octubre 2009 en la media loma y la loma. Los datos fueron analizados en forma gráfica y mediante análisis de la varianza empleando estación climática, especie y tiempo cronológico como factores de clasificación. El CH promedio de las especies a través del tiempo presentó una amplitud estacional marcada, entre 4-5% en invierno-primavera y mayor al 150% en verano-otoño. Las especies nativas presentaron un CH significativamente menor que P. maximum y más bajo que el umbral de extinción teórico (CH=30%) indicando que en la región chaqueña, como en otros ecosistemas, las gramíneas y sus formaciones vegetales son el combustible por donde se propaga el fuego. La dinámica temporal de CH podría ser representada por una sinusoide. La correlación entre CH y la máxima humedad relativa entre fechas de muestreo fue significativa. Ambos resultados sugieren que es factible usar funciones matemáticas conocidas y métodos indirectos para predecir CH y la ‘inflamabilidad’ del combustible en las estaciones climáticas, facilitando la predicción del comportamiento de fuego.Fire is a common event in the Chaco region of Argentina. The fuel moisture content (CH, %) is a factor defining flammability. Its changes throughout time could be used as an index of fire risk, to understand fire ecology, and for planning the use of prescribed fire. We assessed CH dynamics in three ecological sites (≈fuel models): samples with Elionorus muticus as dominant species (lowland, savanna); Trichloris pluriflora y Pappopphorum pappipherum (midland, parkand) and an exotic species Panicum máximum cv Gatton (upland, roller-chopped secondary forest). CH was monitored using the gravimetric method every month in the lowland during 1992; and every 10-15 days from May 2008 to October 2009 in the midland and upland sites. Data were analyzed graphically and with analysis of variance using season, chronological time and species as classification factors. The average CH of the species presented a marked seasonal trend, with a large amplitude, from 4-5% in the winter to above 150 % in summer and fall, respectively. The CH of the native species was significantly lower than P. maximum, and also lower than the extinction threshold (CH = 30 %) suggesting that in the Chaco region, as well as in other ecosystems, grasses are the fuel where fire starts and propagate to other plant communities. Correlation between CH and the maximum air relative humidity observed between sampling dates was significant. The latter fact and the sinusoidal pattern of CH suggest that may be feasible the use of known mathematical functions and indirect methods to predict CH, helping in predict fire behavior throughout the seasons.EEA Santiago del EsteroFil: Kunst, Carlos Roberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santiago del Estero; ArgentinaFil: Ledesma, Roxana Ramona. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santiago del Estero; ArgentinaFil: Bravo, Sandra. Universidad Nacional de Santiago del Estero. Facultad de Ciencias Forestales. Cátedra de Botánica; ArgentinaFil: Defossé, Guillermo E. Centro de Investigación y Extensión Forestal Andino Patagónico; Argentina. Universidad Nacional de la Patagonia San Juan Bosco. Sede Esquel; ArgentinaFil: Godoy, Jose Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santiago del Estero; ArgentinaFil: Navarrete, Victor Del Carmen. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santiago del Estero; ArgentinaFil: Jaime, Napoleon Ar. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santiago del Estero; Argentin

Network-based models for social recommender systems

With the overwhelming online products available in recent years, there is an increasing need to filter and deliver relevant personalized advice for users. Recommender systems solve this problem by modeling and predicting individual preferences for a great variety of items such as movies, books or research articles. In this chapter, we explore rigorous network-based models that outperform leading approaches for recommendation. The network models we consider are based on the explicit assumption that there are groups of individuals and of items, and that the preferences of an individual for an item are determined only by their group memberships. The accurate prediction of individual user preferences over items can be accomplished by different methodologies, such as Monte Carlo sampling or Expectation-Maximization methods, the latter resulting in a scalable algorithm which is suitable for large datasets

Clinical Course and Outcomes of Small Supratentorial Intracerebral Hematomas.

Intracerebral hemorrhage (ICH) volume, particularly if ≥30 mL, is a major determinant of poor outcome. We used a multinational ICH data registry to study the characteristics, course, and outcomes of supratentorial hematomas with volumes <30 mL.Basic characteristics, clinical and radiological course, and 30-day outcomes of these patients were recorded. Outcomes were categorized as early neurological deterioration (END), hematoma expansion, Glasgow Outcome Scale (GOS), and in-hospital death. Poor outcome was defined as composite of in-hospital death and severe disability (GOS ≤ 3). Comparison was conducted based on hemorrhage location. Logistic regression using dichotomized outcome scales was applied to determine predictors of poor outcome.Among 375 cases of supratentorial ICH with volumes <30 mL, expansion and END rates were 19.2% and 7.5%, respectively. Hemorrhage growth was independently associated with END (odds ratio: 28.7, 95% confidence interval [CI]: 8.51-96.5; P < .0001). Expansion rates did not differ according to ICH location. Overall, 13.9% (exact binomial 95% CI: 10.5-17.8) died in the hospital and 29.1% (CI: 24.5-34.0) had severe disability at 30 days; there was a cumulative poor outcome rate of 42.9% (CI: 37.9-48.1). Age, admission Glasgow Coma Scale, intraventricular extension, and END were independently associated with poor outcome. There was no difference in poor outcome rates between lobar and deep locations (40.2% versus 43.8%, P = .56).Patients with supratentorial ICH <30 mL have high rates of poor outcome at 30 days, regardless of location. Nearly 1 in 5 hematomas <30 mL expands, leading to END or death

C-Reactive Protein Predicts Hematoma Growth in Intracerebral Hemorrhage

Background and Purpose—Early hematoma growth (EHG) occurs in about one third of patients with spontaneous intracerebral hemorrhage. The main aim of this study was to investigate the potential of plasma C-reactive protein (CRP) for predicting EHG after acute spontaneous intracerebral hemorrhage. Methods—Plasma CRP was measured within 6 hours of onset (median, 120 minutes) in 399 patients with primary or vitamin K antagonist–associated spontaneous intracerebral hemorrhage and without recent infection. Computed tomography brain scans were performed at baseline and repeated within 24 hours (median, 22 hours). The primary outcome was EHG, defined as absolute growth >12.5 cm3 or relative growth >33%. Secondary outcomes included early neurological worsening (ENW) using the Glasgow Coma Scale and 30-day mortality. Multivariable regression analyses were used to evaluate associations of CRP concentration and outcomes. Kaplan–Meier analysis was used for survival. Results—EHG occurred in 25.8%, ENW in 19.3%, and mortality was 31.8% at 30 days. Thirty-day mortality was significantly higher in patients with ENW (hazard ratio, 3.21; 95% confidence interval, 2.00–5.17; P10 mg/L independently predicted EHG (odds ratio, 4.71; 95% confidence interval, 2.75–8.06; P<0.0001) and ENW (odds ratio, 2.70; 95% confidence interval, 1.50–4.84; P=0.0009). Conclusions—CRP>10 mg/L is independently predictive of EHG and ENW, both of which are associated with increased mortality. Inflammation may be important in contributing to EHG and warrants further investigation

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98