Pervasive Hitchhiking at Coding and Regulatory Sites in Humans

Much effort and interest have focused on assessing the importance of natural selection, particularly positive natural selection, in shaping the human genome. Although scans for positive selection have identified candidate loci that may be associated with positive selection in humans, such scans do not indicate whether adaptation is frequent in general in humans. Studies based on the reasoning of the MacDonald–Kreitman test, which, in principle, can be used to evaluate the extent of positive selection, suggested that adaptation is detectable in the human genome but that it is less common than in Drosophila or Escherichia coli. Both positive and purifying natural selection at functional sites should affect levels and patterns of polymorphism at linked nonfunctional sites. Here, we search for these effects by analyzing patterns of neutral polymorphism in humans in relation to the rates of recombination, functional density, and functional divergence with chimpanzees. We find that the levels of neutral polymorphism are lower in the regions of lower recombination and in the regions of higher functional density or divergence. These correlations persist after controlling for the variation in GC content, density of simple repeats, selective constraint, mutation rate, and depth of sequencing coverage. We argue that these results are most plausibly explained by the effects of natural selection at functional sites—either recurrent selective sweeps or background selection—on the levels of linked neutral polymorphism. Natural selection at both coding and regulatory sites appears to affect linked neutral polymorphism, reducing neutral polymorphism by 6% genome-wide and by 11% in the gene-rich half of the human genome. These findings suggest that the effects of natural selection at linked sites cannot be ignored in the study of neutral human polymorphism

MBEToolbox: a Matlab toolbox for sequence data analysis in molecular biology and evolution

BACKGROUND: MATLAB is a high-performance language for technical computing, integrating computation, visualization, and programming in an easy-to-use environment. It has been widely used in many areas, such as mathematics and computation, algorithm development, data acquisition, modeling, simulation, and scientific and engineering graphics. However, few functions are freely available in MATLAB to perform the sequence data analyses specifically required for molecular biology and evolution. RESULTS: We have developed a MATLAB toolbox, called MBEToolbox, aimed at filling this gap by offering efficient implementations of the most needed functions in molecular biology and evolution. It can be used to manipulate aligned sequences, calculate evolutionary distances, estimate synonymous and nonsynonymous substitution rates, and infer phylogenetic trees. Moreover, it provides an extensible, functional framework for users with more specialized requirements to explore and analyze aligned nucleotide or protein sequences from an evolutionary perspective. The full functions in the toolbox are accessible through the command-line for seasoned MATLAB users. A graphical user interface, that may be especially useful for non-specialist end users, is also provided. CONCLUSION: MBEToolbox is a useful tool that can aid in the exploration, interpretation and visualization of data in molecular biology and evolution. The software is publicly available at and

MBEToolbox 2.0: An enhanced version of a MATLAB toolbox for Molecular Biology and Evolution

MBEToolbox is an extensible MATLAB-based software package for analysis of DNA and protein sequences. MBEToolbox version 2.0 includes enhanced functions for phylogenetic analyses by the maximum likelihood method. For example, it is capable of estimating the synonymous and nonsynonymous substitution rates using a novel or several known codon substitution models. MBEToolbox 2.0 introduces new functions for estimating site-specific evolutionary rates by using a maximum likelihood method or an empirical Bayesian method. It also incorporates several different methods for recombination detection. Multi-platform versions of the software are freely available at http://www.bioinformatics.org/mbetoolbox/

Wait-learning: Leveraging conversational dead time for second language education

Second-language learners are often unable to find time for language practice due to constraints in their daily lives. In this paper, we examine how brief moments of waiting during a person's existing social conversations can be leveraged for second language practice, even if the conversation is exchanged in the first language. We present an instant messaging (IM) prototype, WaitChatter, that supports the notion of wait-learning by displaying contextually relevant foreign language vocabulary and micro-quizzes while the user awaits a response from her conversant. The foreign translations are displayed just-in-time in the context of the conversation to promote incidental learning. In a preliminary study of WaitChatter, we found that participants were able to integrate second language learning into their existing instant messaging activities, and that a particularly opportune time to embed foreign language elements may be immediately after the learner sends a chat message.Lincoln Laborator

Crystal and Electronic Structures of the Complex Hydride Li₄BN₃H₁₀

The crystal structure of Li4BN3H10 was investigated using powder neutron diffraction with high sensitivity. The compound crystallizes in the cubic space group 213 with lattice parameters a=10.645 19(52) Å with an ordered arrangement of [NH2]−1 and [BH4]−1 anions in a molar ratio of 3:1. The bond lengths between the nearest nitrogen and hydrogen atoms are 1.04(4) and 1.14(4) Å. The bond angle between H(1)-N-H(2) is about 126(6)°, while those between H(3)-B-H(3) and H(3)-B-H(4) are about 109(6)°-110(7)°. There are three different Li sites surrounded by [NH2]−1 and [BH4]−1 anions in distorted tetrahedral configurations. The Li(3)-B and Li(3)-N bond distances are about 1.72(3) and 2.32(2) Å, respectively, while the Li(1)-N and Li(2)-N distances are both around 2.09 Å. The strong bonding of Li(3) to the [BH4]−1 and the weaker Li(3)-[NH2]−1 bond are evidenced by the presence of the LiBH4 moiety in a projection of the crystal structure onto the a-b plane. First-principle calculations have been performed based on the structural data. Analyses of the density of states and charge density indicate that H(1) and H(2) strongly interact with N, and H(3) and H(4) interact with B to form [NH2]−1 and [BH4]−1, respectively. It is confirmed that Li(1) and Li(2) are strongly bonded to N and Li(3) is strongly bonded to B. These results are significantly different from some of the previous studies

Keck/Palomar Cosmic Web Imagers (KCWI/PCWI) Reveal an Enormous Lyα\alpha Nebula in an Extremely Overdense QSO Pair Field at z=2.45z=2.45

Enormous Ly$\alpha$ nebulae (ELANe) represent the extrema of Ly$\alpha$ nebulosities. They have detected extents of $>200$ kpc in Ly$\alpha$ and Ly$\alpha$ luminosities $>10^{44}$ erg s$^{-1}$. The ELAN population is an ideal laboratory to study the interactions between galaxies and the intergalactic/circumgalactic medium (IGM/CGM) given their brightness and sizes. The current sample size of ELANe is still very small, and the few $z\approx2$ ELANe discovered to date are all associated with local overdensities of active galactic nuclei (AGNs). Inspired by these results, we have initiated a survey of ELANe associated with QSO pairs using the Palomar and Keck Cosmic Web Imagers (PCWI/KCWI). In this letter, we present our first result: the discovery of ELAN0101+0201 associated with a QSO pair at $z=2.45$. Our PCWI discovery data shows that, above a 2-$\sigma$ surface brightness of $1.2\times10^{-17}$ \sbunit, the end-to-end size of ELAN0101+0201 is $\gtrsim 232$ kpc. We have conducted follow-up observations using KCWI, resolving multiple Ly$\alpha$ emitting sources within the rectangular field-of-view of $\approx 130\times165$ projected kpc$^2$, and obtaining their emission line profiles at high signal-to-noise ratios. Combining both KCWI and PCWI, our observations confirm that ELAN0101+0201 resides in an extremely overdense environment. Our observations further support that a large amount of cool ($T\sim10^4$K) gas could exist in massive halos (M$\gtrsim10^{13}$M$_\odot$) at $z\approx2$. Future observations on a larger sample of similar systems will provide statistics of how cool gas is distributed in massive overdensities at high-redshift and strongly constrain the evolution of the intracluster medium (ICM).Comment: Submitted to Astrophysical Journal Letter, 9 pages, 4 figures, Comments Welcom

Rate equations for nitrogen molecules in ultrashort and intense x-ray pulses

We study theoretically the quantum dynamics of nitrogen molecules (N2) exposed to intense and ultrafast x-rays at a wavelength of 1.1 nm (1100eV photon energy) from the Linac Coherent Light Source (LCLS) free electron laser. Molecular rate equations are derived to describe the intertwined photoionization, decay, and dissociation processes occurring for N2. This model complements our earlier phenomenological approaches, the single-atom, symmetric-sharing, and fragmentation-matrix models of 2012 (J. Chem. Phys. 136 214310). Our rate-equations are used to obtain the effective pulse energy at the sample and the time scale for the dissociation of the metastable dication . This leads to a very good agreement between the theoretically and experimentally determined ion yields and, consequently, the average charge states. The effective pulse energy is found to decrease with shortening pulse duration. This variation together with a change in the molecular fragmentation pattern and frustrated absorption - an effect that reduces absorption of x-rays due to (double) core hole formation - are the causes for the drop of the average charge state with shortening LCLS pulse duration discovered previously