Exploring the Counterion Atmosphere around DNA: What Can Be Learned from Molecular Dynamics Simulations?

AbstractThe counterion distribution around a DNA dodecamer (5′-CGCGAATTCGCG-3′) is analyzed using both standard and novel techniques based on state of the art molecular dynamics simulations. Specifically, we have explored the population of Na+ in the minor groove of DNA duplex, and whether or not a string of Na+ can replace the spine of hydration in the narrow AATT minor groove. The results suggest that the insertion of Na+ in the minor groove is a very rare event, but that when once the ion finds specific sites deep inside the groove it can reside there for very long periods of time. According to our simulation the presence of Na+ inside the groove does not have a dramatic influence in the structure or dynamics of the duplex DNA. The ability of current MD simulations to obtain equilibrated pictures of the counterion atmosphere around DNA is critically discussed

High performance computation of landscape genomic models integrating local indices of spatial association

Since its introduction, landscape genomics has developed quickly with the increasing availability of both molecular and topo-climatic data. The current challenges of the field mainly involve processing large numbers of models and disentangling selection from demography. Several methods address the latter, either by estimating a neutral model from population structure or by inferring simultaneously environmental and demographic effects. Here we present Sam$\beta$ada, an integrated approach to study signatures of local adaptation, providing rapid processing of whole genome data and enabling assessment of spatial association using molecular markers. Specifically, candidate loci to adaptation are identified by automatically assessing genome-environment associations. In complement, measuring the Local Indicators of Spatial Association (LISA) for these candidate loci allows to detect whether similar genotypes tend to gather in space, which constitutes a useful indication of the possible kinship relationship between individuals. In this paper, we also analyze SNP data from Ugandan cattle to detect signatures of local adaptation with Sam$\beta$ada, BayEnv, LFMM and an outlier method (FDIST approach in Arlequin) and compare their results. Sam$\beta$ada is an open source software for Windows, Linux and MacOS X available at \url{http://lasig.epfl.ch/sambada}Comment: 1 figure in text, 1 figure in supplementary material The structure of the article was modified and some explanations were updated. The methods and results presented are the same as in the previous versio

Capital social e información para la salud en el contexto del modo de vida de agricultores de pequeña escala

The study explores the relationship between social capital and health information among small-scale farmers in the context of their livelihoods. Having such information could promote the use of agriculture practices with fewer health impacts by reducing farmers’ exposure to highly toxic pesticides. We implemented a longitudinal study design with measurements in July 2007 (T1) and February 2010 (T2), within 12 agricultural communities in Ecuador (n=208 farmers). The dependent variables were based on information regarding agricultural production practices, among them: integrated pest management (IPM) and pesticide toxicity. Independent variables included participation in organizations and social cohesion, among other aspects of social capital. Results suggest that health information is disseminated through structures of social capital, depending on its value of use in the context of the mode of production in which small scale agriculture is developed.El estudio explora la relación entre el capital social y la información para la salud en agricultores de pequeña escala, en el contexto de su modo de vida. Tener información al respecto promovería la adopción de prácticas agrícolas con menos impacto en su salud debido a la reducción del uso de pesticidas de alta toxicidad. La investigación se desarrolló a través de un diseño longitudinal de medidas repetidas, en julio de 2007 (T1) y febrero de 2010 (T2), en 12 comunidades agrícolas de Ecuador (n=208). La información respecto a las prácticas de producción agrícola, entre ellas, el manejo integrado de plagas, y la toxicidad de los pesticidas constituyeron las variables dependientes. La participación en organizaciones, y la cohesión social, entre otros aspectos del capital social fueron tratados en el análisis como variables independientes. Los hallazgos sugieren que la información para la salud es transmitida por las estructuras del capital social en dependencia de su valor de uso en el marco del modo de producción agrícola

Ecología trófica del Liso (Rhamdia quelen Quoy & Gaimard, 1824) en el río Sinú, Colombia

RESUMEN Objetivo. Estudiar la ecología trófica del Liso en el río Sinú como contribución al conocimiento de su biología y ecología, a su preservación en el medio natural y al ordenamiento de su pesquería en la cuenca. Materiales y métodos. El contenido estomacal se evaluó con el Coeficiente de vacuidad, Grado de digestión, Frecuencia de ocurrencia, Frecuencia numérica, Gravimetría, Índice de importancia relativa (IIR) y la relación longitud intestinal (LI)-longitud total (LT). Resultados. El 38.2% de los estómagos estaban vacíos y el 92.5% de las presas estaban medio digeridas, identificándose 5 grupos alimentarios: Peces, Crustáceos, Insectos, Material vegetal y Otros. Peces, conformado por Cachana, Cocobolo, Mayupa, Sardina y Restos de peces, fue la presa más frecuente (69.9%), abundante (45.5%) y con mayor composición por peso (76.8%). El Índice de importancia relativa (IIR) indica que Peces fue el alimento principal (IIR =53.7%), y que las demás presas eran de baja importancia relativa, circunstanciales o incidentales. Conclusiones. Los resultados alcanzados en este estudio indican que el Liso es un pez con hábitos alimentarios nocturnos y carnívoros, con tendencia a consumir Peces

iSKID: From integrated pilot scale runs to GMP implementation approach

One of the most compelling business reasons for integrated processing is the ability to de-risk capital investment due to a significantly more productive process that takes less space and fewer campaigns to generate clinical and commercial material. Boehringer Ingelheim and Pfizer developed the iSKID, a fully integrated and automated system that hydraulically links the perfusion bioreactor with several downstream unit operations (2xProtein A columns, continuous viral inactivation, AEX in flow through mode, and SPTFF). The Protein A elution cycles are discrete and separated by \u3e2hrs, allowing the ability to discard cycles that do not meet process specifications. The discreteness between product cycles and hydraulic linkage enables the sanitization between cycles for a robust bioburden control strategy. Each cycle is captured in a single use mixer (SUM), where the product is pooled in stable conditions until viral filtration, ultrafiltration/diafiltration and final filtration are performed in batch mode. Identical iSKID prototypes at 100L scale were used at three different sites to generate product quality, process, and bioburden data from three different molecules. The data has been used to understand implementation gaps in GMP facilities and process platforms (CMC1/CMC2). In addition, the team identified specific items to present to the FDA’s Emerging Technology Team (ETT). These items include our strategies for batch definition, microbial control, and process control. In this talk, we will use the data generated from the consistency runs to elaborate on the robustness of the process and touch upon the strategies to be presented to the ETT

SamBada in Uganda: landscape genomics study of traditional cattle breeds with a large SNP dataset

Since its introduction, landscape genomics has developed quickly with the increasing availability of both molecular and topo-climatic data. Current challenges involve processing large numbers of models and disentangling selection from demography. Several methods address the latter, either by estimating a neutral model from population structure or by inferring simultaneously environmental and demographic effects. Here we present Sam!ada, an integrated software for landscape genomic analysis of large datasets. This tool was developed in the framework of NextGen with the objective of characterising traditional Ugandan cattle breeds using single nucleotide polymorphisms (SNPs) data

Theoretical study of large conformational transitions in DNA: the B↔A conformational change in water and ethanol/water

We explore here the possibility of determining theoretically the free energy change associated with large conformational transitions in DNA, like the solvent-induced B⇔A conformational change. We find that a combination of targeted molecular dynamics (tMD) and the weighted histogram analysis method (WHAM) can be used to trace this transition in both water and ethanol/water mixture. The pathway of the transition in the A→B direction mirrors the B→A pathway, and is dominated by two processes that occur somewhat independently: local changes in sugar puckering and global rearrangements (particularly twist and roll) in the structure. The B→A transition is found to be a quasi-harmonic process, which follows closely the first spontaneous deformation mode of B-DNA, showing that a physiologically-relevant deformation is in coded in the flexibility pattern of DNA

A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA

It is well recognized that base sequence exerts a significant influence on the properties of DNA and plays a significant role in protein–DNA interactions vital for cellular processes. Understanding and predicting base sequence effects requires an extensive structural and dynamic dataset which is currently unavailable from experiment. A consortium of laboratories was consequently formed to obtain this information using molecular simulations. This article describes results providing information not only on all 10 unique base pair steps, but also on all possible nearest-neighbor effects on these steps. These results are derived from simulations of 50–100 ns on 39 different DNA oligomers in explicit solvent and using a physiological salt concentration. We demonstrate that the simulations are converged in terms of helical and backbone parameters. The results show that nearest-neighbor effects on base pair steps are very significant, implying that dinucleotide models are insufficient for predicting sequence-dependent behavior. Flanking base sequences can notably lead to base pair step parameters in dynamic equilibrium between two conformational sub-states. Although this study only provides limited data on next-nearest-neighbor effects, we suggest that such effects should be analyzed before attempting to predict the sequence-dependent behavior of DNA