Evidence for adaptive introgression of exons across a hybrid swarm in deer

Background: Secondary contact between closely related lineages can result in a variety of outcomes, including hybridization, depending upon the strength of reproductive barriers. By examining the extent to which different parts of the genome introgress, it is possible to infer the strength of selection and gain insight into the evolutionary trajectory of lineages. Following secondary contact approximately 8000 years ago in the Pacific Northwest, mule deer (Odocoileus hemionus hemionus) and black-tailed deer (O. h. columbianus) formed a hybrid swarm along the Cascade mountain range despite substantial differences in body size (up to two times) and habitat preference. In this study, we examined genetic population structure, extent of introgression, and selection pressures in freely interbreeding populations of mule deer and black-tailed deer using mitochondrial DNA sequences, 9 microsatellite loci, and 95 SNPs from protein-coding genes. Results: We observed bi-directional hybridization and classified approximately one third of the 172 individuals as hybrids, almost all of which were beyond the F1 generation. High genetic differentiation between black-tailed deer and mule deer at protein-coding genes suggests that there is positive divergent selection, though selection on these loci is relatively weak. Contrary to predictions, there was not greater selection on protein-coding genes thought to be associated with immune function and mate choice. Geographic cline analyses were consistent across genetic markers, suggesting long-term stability (over hundreds of generations), and indicated that the center of the hybrid swarm is 20-30 km to the east of the Cascades ridgeline, where there is a steep ecological transition from wet, forested habitat to dry, scrub habitat. Conclusions: Our data are consistent with a genetic boundary between mule deer and black-tailed deer that is porous but maintained by many loci under weak selection having a substantial cumulative effect. The absence of clear reproductive barriers and the consistent centering of geographic clines at a sharp ecotone suggests that ecology is a driver of hybrid swarm dynamics. Adaptive introgression in this study (and others) promotes gene flow and provides valuable insight into selection strength on specific genes and the evolutionary trajectory of hybridizing taxa

Blind Test of Methods for Obtaining 2-D Near-Surface Seismic Velocity Models from First-Arrival Traveltimes

Seismic refraction methods are used in environmental and engineering studies to image the shallow subsurface. We present a blind test of inversion and tomographic refraction analysis methods using a synthetic first-arrival-time dataset that was made available to the community in 2010. The data are realistic in terms of the near-surface velocity model, shot-receiver geometry and the data’s frequency and added noise. Fourteen estimated models were determined by ten participants using eight different inversion algorithms, with the true model unknown to the participants until it was revealed at a session at the 2011 SAGEEP meeting. The estimated models are generally consistent in terms of their large-scale features, demonstrating the robustness of refraction data inversion in general, and the eight inversion algorithms in particular. When compared to the true model, all of the estimated models contain a smooth expression of its two main features: a large offset in the bedrock and the top of a steeply dipping low-velocity fault zone. The estimated models do not contain a subtle low-velocity zone and other fine-scale features, in accord with conventional wisdom. Together, the results support confidence in the reliability and robustness of modern refraction inversion and tomographic Methods

Footprints of spontaneous fluid redistribution on capillary pressure in porous rock

Pore-scale imaging of two-phase flow in porous media shows that pore filling occurs as cooperative events with accompanying spontaneous fluid redistribution in other parts of the pore space. We present a level set method that controls saturation quasi-statically to model experiments controlled by low, constant flow rates and demonstrate that our method can describe the observed displacement mechanisms. The level set approach determines states of capillary equilibrium, which generally are different for displacement protocols constrained by saturation and pressure. Saturation-controlled simulations of drainage in sandstone show spontaneous fluid redistributions with abrupt pressure jumps and cooperative behavior, including snap-off and interface retraction events, consistent with experimental observations. Drainage capillary pressure curves are lower when saturation, rather than pressure, controls displacement. Remarkably, these effects are less significant for imbibition processes where the development of hydraulically connected wetting phase moderates the cooperative behavior and associated pressure jumps.publishedVersio

About the lithospheric structure of central Tibet based on seismic data from the INDEPTH III profile

Signals from 11 shots and 8 earthquakes, and numerous teleseismic events were recorded along the 400-km seismic line INDEPTH III in central Tibet and interpreted together with previous seismic and tectonic data. The abnormal behavior of various mantle phases reveals a complex Moho-transition zone, especially in the northern part of the line, in the Changtang Block, where the lower crust and the mantle show unusually low velocities, a shingled appearance of Pn and no low-velocity layer in the upper crust. The strong east-west anisotropy in the Changtang Block is related to an easterly escape movement of the whole lithosphere, facilitated by the warm and weak layers in the lower crust and the upper mantle, bounded apparently by two prominent west-east running fault zones

Globular cluster systems as tracers of environmental effects on Virgo early-type dwarfs

Early-type dwarfs (dEs) are by far the most abundant galaxy population in nearby clusters. Whether these objects are primordial, or the recent end-products of the different physical mechanisms that can transform galaxies once they enter these high-density environments, is still a matter of debate. Here we present a novel approach to test these scenarios by comparing the properties of the globular cluster systems (GCSs) of Virgo dEs and their potential progenitors with simple predictions from gravitational and hydrodynamical interaction models. We show that low-mass (Mstar < 2E8 Msun) dEs have GCSs consistent with being the descendants of gas-stripped late-type dwarfs. On the other hand, higher mass dEs have properties -including the high mass specific frequencies of their GCSs and their concentrated spatial distribution within Virgo- incompatible with a recent, environmentally-driven evolution. They mostly comprise nucleated systems, but also dEs with recent star formation and/or disc features. Bright, nucleated dEs appear to be a population that has long resided within the cluster potential well, but have surprisingly managed to retain very rich and spatially extended GCSs - possibly an indication of high total masses. Our analysis does not favour violent evolutionary mechanisms that result in significant stellar mass losses, but more gentle processes involving gas removal by a combination of internal and external factors, and highlights the relevant role of initial conditions. Additionally, we briefly comment on the origin of luminous cluster S0s.Comment: 13 pages, 4 figures, accepted for publication in MNRA

Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis

Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce populations of insect pollinator species. Here we present a promising, environment-friendly alternative to current insecticides that targets the insect tyrosine metabolism pathway. A bloodmeal contains high levels of tyrosine, which is toxic to haematophagous insects if it is not degraded and eliminated. RNA interference (RNAi) of either the first two enzymes in the tyrosine degradation pathway (tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD)) was lethal to tsetse. Furthermore, nitisinone (NTBC), an FDA-approved tyrosine catabolism inhibitor, killed tsetse regardless if the drug was orally or topically applied. However, oral administration of NTBC to bumblebees did not affect their survival. Using a novel mathematical model, we show that NTBC could reduce the transmission of African trypanosomiasis in sub-Saharan Africa, thus accelerating current disease elimination programmes

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified