Comparative Transcriptional and Genomic Analysis of Plasmodium falciparum Field Isolates

Mechanisms for differential regulation of gene expression may underlie much of the phenotypic variation and adaptability of malaria parasites. Here we describe transcriptional variation among culture-adapted field isolates of Plasmodium falciparum, the species responsible for most malarial disease. It was found that genes coding for parasite protein export into the red cell cytosol and onto its surface, and genes coding for sexual stage proteins involved in parasite transmission are up-regulated in field isolates compared with long-term laboratory isolates. Much of this variability was associated with the loss of small or large chromosomal segments, or other forms of gene copy number variation that are prevalent in the P. falciparum genome (copy number variants, CNVs). Expression levels of genes inside these segments were correlated to that of genes outside and adjacent to the segment boundaries, and this association declined with distance from the CNV boundary. This observation could not be explained by copy number variation in these adjacent genes. This suggests a local-acting regulatory role for CNVs in transcription of neighboring genes and helps explain the chromosomal clustering that we observed here. Transcriptional co-regulation of physical clusters of adaptive genes may provide a way for the parasite to readily adapt to its highly heterogeneous and strongly selective environment

Exploring the Conformational Transitions of Biomolecular Systems Using a Simple Two-State Anisotropic Network Model

Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints. The two-state potential has a cusp hypersurface in the configuration space where the energies from both the ENMs are equal. We first search for the minimum energy structure on the cusp hypersurface and then treat it as the transition state. The continuous pathway is subsequently constructed by following the steepest descent energy minimization trajectories starting from the transition state on each side of the cusp hypersurface. Application to several systems of broad biological interest such as adenylate kinase, ATP-driven calcium pump SERCA, leucine transporter and glutamate transporter shows that ANMPathway yields results in good agreement with those from other similar methods and with data obtained from all-atom molecular dynamics simulations, in support of the utility of this simple and efficient approach. Notably the method provides experimentally testable predictions, including the formation of non-native contacts during the transition which we were able to detect in two of the systems we studied. An open-access web server has been created to deliver ANMPathway results. © 2014 Das et al

The Spread of Inequality

The causes of socioeconomic inequality have been debated since the time of Plato. Many reasons for the development of stratification have been proposed, from the need for hierarchical control over large-scale irrigation systems to the accumulation of small differences in wealth over time via inheritance processes. However, none of these explains how unequal societies came to completely displace egalitarian cultural norms over time. Our study models demographic consequences associated with the unequal distribution of resources in stratified societies. Agent-based simulation results show that in constant environments, unequal access to resources can be demographically destabilizing, resulting in the outward migration and spread of such societies even when population size is relatively small. In variable environments, stratified societies spread more and are also better able to survive resource shortages by sequestering mortality in the lower classes. The predictions of our simulation are provided modest support by a range of existing empirical studies. In short, the fact that stratified societies today vastly outnumber egalitarian societies may not be due to the transformation of egalitarian norms and structures, but may instead reflect the more rapid migration of stratified societies and consequent conquest or displacement of egalitarian societies over time

Understanding biomolecular motion, recognition, and allostery by use of conformational ensembles

We review the role conformational ensembles can play in the analysis of biomolecular dynamics, molecular recognition, and allostery. We introduce currently available methods for generating ensembles of biomolecules and illustrate their application with relevant examples from the literature. We show how, for binding, conformational ensembles provide a way of distinguishing the competing models of induced fit and conformational selection. For allostery we review the classic models and show how conformational ensembles can play a role in unravelling the intricate pathways of communication that enable allostery to occur. Finally, we discuss the limitations of conformational ensembles and highlight some potential applications for the future

Corporate boards and the performance of Asian firms: A meta-analysis

The prevalence of ownership concentration in Asian firms presents a challenge to the influential agency theory-based understanding of the role of corporate boards. In this paper we develop and test hypotheses about board attributes and firm performance that reflect Asian institutional conditions. We present the first meta-analysis of the relationship between board attributes and performance of Asian firms using a varied set of meta-analytical techniques on a database of 86 studies covering nine Asian countries. First, we find that board structure and composition preferences are influenced by the identity of the concentrated owner. Second, consistent with US data, we find very limited evidence of a direct relationship between board attributes and firm financial performance in the Asian context. Third, we find that the relationship between board structure and composition and firm performance is mediated by the revealed strategic preferences of Asian firms specifically by the level of R&D investment

Perspectives on Disconnects Between Scientific Information and Management Decisions on Post-fire Recovery in Western US

Environmental regulations frequently mandate the use of "best available" science, but ensuring that it is used in decisions around the use and protection of natural resources is often challenging. In the Western US, this relationship between science and management is at the forefront of post-fire land management decisions. Recent fires, post-fire threats (e.g. flooding, erosion), and the role of fire in ecosystem health combine to make post-fire management highly visible and often controversial. This paper uses post-fire management to present a framework for understanding why disconnects between science and management decisions may occur. We argue that attributes of agencies, such as their political or financial incentives, can limit how effectively science is incorporated into decision-making. At the other end of the spectrum, the lack of synthesis or limited data in science can result in disconnects between science-based analysis of post-fire effects and agency policy and decisions. Disconnects also occur because of the interaction between the attributes of agencies and the attributes of science, such as their different spatial and temporal scales of interest. After offering examples of these disconnects in post-fire treatment, the paper concludes with recommendations to reduce disconnects by improving monitoring, increasing synthesis of scientific findings, and directing social-science research toward identifying and deepening understanding of these disconnects

European agricultural landscapes, common agricultural policy and ecosystem services: a review

Since the 1950s, intensification and scale enlargement of agriculture have changed agricultural landscapes across Europe. The intensification and scale enlargement of farming was initially driven by the large-scale application of synthetic fertilizers, mechanization and subsidies of the European Common Agricultural Policy (CAP). Then, after the 1990s, a further intensification and scale enlargement, and land abandonment in less favored areas was caused by globalization of commodity markets and CAP reforms. The landscape changes during the past six decades have changed the flows and values of ecosystem services. Here, we have reviewed the literature on agricultural policies and management, landscape structure and composition, and the contribution of ecosystem services to regional competitiveness. The objective was to define an analytical framework to determine and assess ecosystem services at the landscape scale. In contrast to natural ecosystems, ecosystem service flows and values in agricultural landscapes are often a result of interactions between agricultural management and ecological structures. We describe how land management by farmers and other land managers relates to landscape structure and composition. We also examine the influence of commodity markets and policies on the behavior of land managers. Additionally, we studied the influence of consumer demand on flows and values of the ecosystem services that originate from the agricultural landscape

Modeling working memory: An interference model of complex span

This article introduces a new computational model for the complex-span task, the most popular task for studying working memory. SOB-CS is a two-layer neural network that associates distributed item representations with distributed, overlapping position markers. Memory capacity limits are explained by interference from a superposition of associations. Concurrent processing interferes with memory through involuntary encoding of distractors. Free time in-between distractors is used to remove irrelevant representations, thereby reducing interference. The model accounts for benchmark findings in four areas: (1) effects of processing pace, processing difficulty, and number of processing steps; (2) effects of serial position and error patterns; (3) effects of different kinds of item-distractor similarity; and (4) correlations between span tasks. The model makes several new predictions in these areas, which were confirmed experimentally