On the accumulation of deleterious mutations during range expansions

We investigate the effect of spatial range expansions on the evolution of fitness when beneficial and deleterious mutations co-segregate. We perform individual-based simulations of a uniform linear habitat and complement them with analytical approximations for the evolution of mean fitness at the edge of the expansion. We find that deleterious mutations accumulate steadily on the wave front during range expansions, thus creating an expansion load. Reduced fitness due to the expansion load is not restricted to the wave front but occurs over a large proportion of newly colonized habitats. The expansion load can persist and represent a major fraction of the total mutation load thousands of generations after the expansion. Our results extend qualitatively and quantitatively to two-dimensional expansions. The phenomenon of expansion load may explain growing evidence that populations that have recently expanded, including humans, show an excess of deleterious mutations. To test the predictions of our model, we analyze patterns of neutral and non-neutral genetic diversity in humans and find an excellent fit between theory and data

Why HR is set to fail the big data challenge

Few organisations have made much progress in developing HR analytics capabilities, write Andy Charlwood, Mark Stuart, Ian Kirkpatrick and Mark T Lawrenc

Visualizing genetic constraints

Principal Components Analysis (PCA) is a common way to study the sources of variation in a high-dimensional data set. Typically, the leading principal components are used to understand the variation in the data or to reduce the dimension of the data for subsequent analysis. The remaining principal components are ignored since they explain little of the variation in the data. However, evolutionary biologists gain important insights from these low variation directions. Specifically, they are interested in directions of low genetic variability that are biologically interpretable. These directions are called genetic constraints and indicate directions in which a trait cannot evolve through selection. Here, we propose studying the subspace spanned by low variance principal components by determining vectors in this subspace that are simplest. Our method and accompanying graphical displays enhance the biologist's ability to visualize the subspace and identify interpretable directions of low genetic variability that align with simple directions.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS603 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

SDSS J141624.08+134826.7: Blue L Dwarfs and Non-Equilibrium Chemistry

We present an analysis of the recently discovered blue L dwarf SDSS J141624.08+134826.7. We extend the spectral coverage of its published spectrum to ~4 microns by obtaining a low-resolution L band spectrum with SpeX on the NASA IRTF. The spectrum exhibits a tentative weak CH4 absorption feature at 3.3 microns but is otherwise featureless. We derive the atmospheric parameters of SDSS J141624.08+134826.7 by comparing its 0.7-4.0 micron spectrum to the atmospheric models of Marley and Saumon which include the effects of both condensate cloud formation and non-equilibrium chemistry due to vertical mixing and find the best fitting model has Teff=1700 K, log g=5.5 [cm s-2], fsed=4, and Kzz=10^4 cm2 s-1. The derived effective temperature is significantly cooler than previously estimated but we confirm the suggestion by Bowler et al. that the peculiar spectrum of SDSS J141624.08+134826.7 is primarily a result of thin condensate clouds. In addition, we find strong evidence of vertical mixing in the atmosphere of SDSS J141624.08+134826.7 based on the absence of the deep 3.3 micron CH4 absorption band predicted by models computed in chemical equilibrium. This result suggests that observations of blue L dwarfs are an appealing way to quantitatively estimate the vigor of mixing in the atmospheres of L dwarfs because of the dramatic impact such mixing has on the strength of the 3.3 micron CH4 band in the emergent spectra of L dwarfs with thin condensate clouds.Comment: Accepted for publication in the Astronomical Journa

Pms2 suppresses large expansions of the (GAA·TTC)n sequence in neuronal tissues

Copyright @ 2012 Bourn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Expanded trinucleotide repeat sequences are the cause of several inherited neurodegenerative diseases. Disease pathogenesis is correlated with several features of somatic instability of these sequences, including further large expansions in postmitotic tissues. The presence of somatic expansions in postmitotic tissues is consistent with DNA repair being a major determinant of somatic instability. Indeed, proteins in the mismatch repair (MMR) pathway are required for instability of the expanded (CAG·CTG)(n) sequence, likely via recognition of intrastrand hairpins by MutSβ. It is not clear if or how MMR would affect instability of disease-causing expanded trinucleotide repeat sequences that adopt secondary structures other than hairpins, such as the triplex/R-loop forming (GAA·TTC)(n) sequence that causes Friedreich ataxia. We analyzed somatic instability in transgenic mice that carry an expanded (GAA·TTC)(n) sequence in the context of the human FXN locus and lack the individual MMR proteins Msh2, Msh6 or Pms2. The absence of Msh2 or Msh6 resulted in a dramatic reduction in somatic mutations, indicating that mammalian MMR promotes instability of the (GAA·TTC)(n) sequence via MutSα. The absence of Pms2 resulted in increased accumulation of large expansions in the nervous system (cerebellum, cerebrum, and dorsal root ganglia) but not in non-neuronal tissues (heart and kidney), without affecting the prevalence of contractions. Pms2 suppressed large expansions specifically in tissues showing MutSα-dependent somatic instability, suggesting that they may act on the same lesion or structure associated with the expanded (GAA·TTC)(n) sequence. We conclude that Pms2 specifically suppresses large expansions of a pathogenic trinucleotide repeat sequence in neuronal tissues, possibly acting independently of the canonical MMR pathway.IDB was supported by a postdoctoral fellowship from the National Ataxia Foundation. RMP was supported by Ataxia UK. SA was supported by The Wellcome Trust. This research was made possible by grants from the National Institutes of Health (NIH/NINDS) and the Muscular Dystrophy Association to S.I.B

Identifying Young Brown Dwarfs Using Gravity-Sensitive Spectral Features

We report the initial results of the Brown Dwarf Spectroscopic Survey Gravity Project, to study gravity sensitive features as indicators of youth in brown dwarfs. Low-resolution (R~2000) J-band and optical (R~1000) observations using NIRSPEC and LRIS at the W.M. Keck Observatory reveal transitions of TiO, VO, K I, Na I, Cs I, Rb I, CaH, and FeH. By comparing these features in late-type giants and in old field dwarfs we show that they are sensitive to the gravity (g = GM/R^2) of the object. Using low-gravity spectral signatures as age indicators, we observed and analyzed J-band and optical spectra of two young brown dwarfs, G 196-3B (20-300 Myr) and KPNO Tau-4 (1-2 Myr), and two possible low mass brown dwarfs in the sigma Orionis cluster (3-7 Myr). We report the identification of the phi bands of TiO near 1.24 microns and the A-X band of VO near 1.18 microns together with extremely weak J-band lines of K I in KPNO-Tau4. This is the first detection of TiO and VO in the J-band in a sub-stellar mass object. The optical spectrum of KPNO-Tau4 exhibits weak K I and Na I lines, weak absorption by CaH, and strong VO bands, also signatures of a lower gravity atmosphere. G 196-3B shows absorption features in both wavelength regions like those of KPNO-Tau4 suggesting that its age and mass are at the lower end of published estimates. Whereas sigma Ori 51 appears to be consistent with a young sub-stellar object, sigma Ori 47 shows signatures of high gravity most closely resembling an old L1.5/L0, and can not be a member of the sigma Orionis cluster.Comment: 14 pages, 4 figures. To appear in the January 10, 2004 issue of the Astrophysical Journa

Surface Gravities for 228 M, L, and T Dwarfs in the NIRSPEC Brown Dwarf Spectroscopic Survey

We combine 131 new medium-resolution (R~2000) J-band spectra of M, L, and T dwarfs from the Keck NIRSPEC Brown Dwarf Spectroscopic Survey (BDSS) with 97 previously published BDSS spectra to study surface-gravity-sensitive indices for 228 low-mass stars and brown dwarfs spanning spectral types M5-T9. Specifically, we use an established set of spectral indices to determine surface gravity classifications for all M6-L7 objects in our sample by measuring equivalent widths (EW) of the K I lines at 1.1692, 1.1778, 1.2529 um, and the 1.2 um FeHJ absorption index. Our results are consistent with previous surface gravity measurements, showing a distinct double peak - at ~L5 and T5 - in K I EW as a function of spectral type. We analyze K I EWs of 73 objects of known ages and find a linear trend between log(Age) and EW. From this relationship, we assign age ranges to the very low gravity, intermediate gravity, and field gravity designations for spectral types M6-L0. Interestingly, the ages probed by these designations remain broad, change with spectral type, and depend on the gravity sensitive index used. Gravity designations are useful indicators of the possibility of youth, but current datasets cannot be used to provide a precise age estimate.Comment: 33 pages, 13 figures, ApJ in pres

Sex Differences in Recombination in Sticklebacks.

Recombination often differs markedly between males and females. Here we present the first analysis of sex-specific recombination in Gasterosteus sticklebacks. Using whole-genome sequencing of 15 crosses between G. aculeatus and G. nipponicus, we localized 698 crossovers with a median resolution of 2.3 kb. We also used a bioinformatic approach to infer historical sex-averaged recombination patterns for both species. Recombination is greater in females than males on all chromosomes, and overall map length is 1.64 times longer in females. The locations of crossovers differ strikingly between sexes. Crossovers cluster toward chromosome ends in males, but are distributed more evenly across chromosomes in females. Suppression of recombination near the centromeres in males causes crossovers to cluster at the ends of long arms in acrocentric chromosomes, and greatly reduces crossing over on short arms. The effect of centromeres on recombination is much weaker in females. Genomic differentiation between G. aculeatus and G. nipponicus is strongly correlated with recombination rate, and patterns of differentiation along chromosomes are strongly influenced by male-specific telomere and centromere effects. We found no evidence for fine-scale correlations between recombination and local gene content in either sex. We discuss hypotheses for the origin of sexual dimorphism in recombination and its consequences for sexually antagonistic selection and sex chromosome evolution

A Prospective Evaluation of Opioid Utilization After Upper-Extremity Surgical Procedures: Identifying Consumption Patterns and Determining Prescribing Guidelines.

BACKGROUND: Although adequate management of postoperative pain with oral analgesics is an important aspect of surgical procedures, inadvertent overprescribing can lead to excess availability of opioids in the community for potential diversion. The purpose of our study was to prospectively evaluate opioid consumption following outpatient upper-extremity surgical procedures to determine opioid utilization patterns and to develop prescribing guidelines. METHODS: All patients undergoing outpatient upper-extremity surgical procedures over a consecutive 6-month period had the following prospective data collected: patient demographic characteristics, surgical details, anesthesia type, and opioid prescription and consumption patterns. Analysis of variance and post hoc comparisons were performed using t tests, with the p value for multiple pairwise tests adjusted by the Bonferroni correction. RESULTS: A total of 1,416 patients with a mean age of 56 years (range, 18 to 93 years) were included in the study. Surgeons prescribed a mean total of 24 pills, and patients reported consuming a mean total of 8.1 pills, resulting in a utilization rate of 34%. Patients undergoing soft-tissue procedures reported requiring fewer opioids (5.1 pills for 2.2 days) compared with fracture surgical procedures (13.0 pills for 4.5 days) or joint procedures (14.5 pills for 5.0 days) (p \u3c 0.001). Patients who underwent wrist surgical procedures required a mean number of 7.5 pills for 3.1 days and those who underwent hand surgical procedures required a mean number of 7.7 pills for 2.9 days, compared with patients who underwent forearm or elbow surgical procedures (11.1 pills) and those who underwent upper arm or shoulder surgical procedures (22.0 pills) (p \u3c 0.01). Procedure type, anatomic location, anesthesia type, age, and type of insurance were also all significantly associated with reported opioid consumption (p \u3c 0.001). CONCLUSIONS: In this large, prospective evaluation of postoperative opioid consumption, we found that patients are being prescribed approximately 3 times greater opioid medications than needed following upper-extremity surgical procedures. We have provided general prescribing guidelines, and we recommend that surgeons carefully examine their patients\u27 opioid utilization and consider customizing their opioid prescriptions on the basis of anatomic location and procedure type to prescribe the optimal amount of opioids while avoiding dissemination of excess opioids