MHC-linked and un-linked class I genes in the wallaby

Background: MHC class I antigens are encoded by a rapidly evolving gene family comprising classical and non-classical genes that are found in all vertebrates and involved in diverse immune functions. However, there is a fundamental difference between the organization of class I genes in mammals and non-mammals. Non-mammals have a single classical gene responsible for antigen presentation, which is linked to the antigen processing genes, including TAP. This organization allows co-evolution of advantageous class Ia/ TAP haplotypes. In contrast, mammals have multiple classical genes within the MHC, which are separated from the antigen processing genes by class III genes. It has been hypothesized that separation of classical class I genes from antigen processing genes in mammals allowed them to duplicate. We investigated this hypothesis by characterizing the class I genes of the tammar wallaby, a model marsupial that has a novel MHC organization, with class I genes located within the MHC and 10 other chromosomal locations. Results: Sequence analysis of 14 BACs containing 15 class I genes revealed that nine class I genes, including one to three classical class I, are not linked to the MHC but are scattered throughout the genome. Kangaroo Endogenous Retroviruses (KERVs) were identified flanking the MHC un-linked class I. The wallaby MHC contains four non-classical class I, interspersed with antigen processing genes. Clear orthologs of non-classical class I are conserved in distant marsupial lineages. Conclusion: We demonstrate that classical class I genes are not linked to antigen processing genes in the wallaby and provide evidence that retroviral elements were involved in their movement. The presence of retroviral elements most likely facilitated the formation of recombination hotspots and subsequent diversification of class I genes. The classical class I have moved away from antigen processing genes in eutherian mammals and the wallaby independently, but both lineages appear to have benefited from this loss of linkage by increasing the number of classical genes, perhaps enabling response to a wider range of pathogens. The discovery of non-classical orthologs between distantly related marsupial species is unusual for the rapidly evolving class I genes and may indicate an important marsupial specific function

Perceptions of genetic risk, testing, and counseling among individuals with eating disorders

Objective: Eating disorders develop as a result of genetic and environmental factors. Given that they are multifactorial conditions with a genetic component, they fall within the scope of practice for genetic counseling, but people with these conditions are rarely referred. The purpose of this study was to explore the perceptions of causes of eating disorders, recurrence risk, and interest in genetic counseling and testing among individuals with eating disorders. Method: An online survey comprising both multiple choice and free form text questions, vignettes about genetic counseling, and the ED100K (validated eating disorder diagnostic questionnaire) was shared via support organizations and prominent bloggers in the eating disorders community to recruit individuals with a personal history of an eating disorder from November 2018 to February 2019. Results: In total, 107 participants completed the survey. They perceived that both experiences and genetics were important factors in the development of their eating disorder. All responding participants overestimated the risk for recurrence of eating disorders in children, often by a large margin, and a notable minority reported that their experience with an eating disorder had a negative influence on their childbearing decisions. After imagined experience of genetic counseling, participants reported significantly decreased feelings of stigma, shame, and guilt. Most participants expressed interest in genetic counseling; fewer were interested in genetic testing. Discussion: Genetic counseling may benefit individuals with eating disorders by providing accurate recurrence risk information and reducing feelings of guilt, stigma, and shame, which may in turn encourage earlier support seeking and recovery

License prices for financially constrained firms

It is often alleged that high auction prices inhibit service deployment. We investigate this claim under the extreme case of financially constrained bidders. If demand is just slightly elastic, auctions maximize consumer surplus if consumer surplus is a convex function of quantity (a common assumption), or if consumer surplus is concave and the proportion of expenditure spent on deployment is greater than one over the elasticity of demand. The latter condition appears to be true for most of the large telecom auctions in the US and Europe. Thus, even if high auction prices inhibit service deployment, auctions appear to be optimal from the consumers’ point of view

The BES f_0(1810): a new glueball candidate

We analyze the f_0(1810) state recently observed by the BES collaboration via radiative J/\psi decay to a resonant \phi\omega spectrum and confront it with DM2 data and glueball theory. The DM2 group only measured \omega\omega decays and reported a pseudoscalar but no scalar resonance in this mass region. A rescattering mechanism from the open flavored KKbar decay channel is considered to explain why the resonance is only seen in the flavor asymmetric \omega\phi branch along with a discussion of positive C parity charmonia decays to strengthen the case for preferred open flavor glueball decays. We also calculate the total glueball decay width to be roughly 100 MeV, in agreement with the narrow, newly found f_0, and smaller than the expected estimate of 200-400 MeV. We conclude that this discovered scalar hadron is a solid glueball candidate and deserves further experimental investigation, especially in the K-Kbar channel. Finally we comment on other, but less likely, possible assignments for this state.Comment: 11 pages, 4 figures. Major substantive additions, including an ab-initio, QCD-based computation of the glueball inclusive decay width, evaluation of final state effects, and enhanced discussion of several alternative possibilities. Our conclusions are unchanged: the BES f_0(1810) is a promising glueball candidat

A Study on Multimemetic Estimation of Distribution Algorithms

PPSN 2014, LNCS 8672, pp. 322-331Multimemetic algorithms (MMAs) are memetic algorithms in which memes (interpreted as non-genetic expressions of problem solving strategies) are explicitly represented and evolved alongside genotypes. This process is commonly approached using the standard genetic procedures of recombination and mutation to manipulate directly information at the memetic level. We consider an alternative approach based on the use of estimation of distribution algorithms to carry on this self-adaptive memetic optimization process. We study the application of different EDAs to this end, and provide an extensive experimental evaluation. It is shown that elitism is essential to achieve top performance, and that elitist versions of multimemetic EDAs using bivariate probabilistic models are capable of outperforming genetic MMAs.This work is partially supported by MICINN project ANYSELF (TIN2011-28627-C04-01), by Junta de Andalucía project DNEMESIS (P10-TIC-6083) and by Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tech

Long-term exposures to air pollution and the risk of atrial fibrillation in the women’s health initiative cohort

BACKGROUND: Atrial fibrillation (AF) is associated with substantial morbidity and mortality. Short-term exposures to air pollution have been associated with AF triggering; less is known regarding associations between long-term air pollution exposures and AF incidence. OBJECTIVES: Our objective was to assess the association between long-term exposures to air pollution and distance to road on incidence of AF in a cohort of U.S. women. METHODS: We assessed the association of high resolution spatiotemporal model predictions of long-term exposures to particulate matter (PM10 and PM2:5 ), sulfur dioxide (SO2 ), nitrogen dioxide (NO2 ), and distance to major roads with incidence of AF diagnosis, identified through Medicare link-age, among 83,117 women in the prospective Women’s Health Initiative cohort, followed from enrollment in Medicare through December 2012, incidence of AF, or death. Using time-varying Cox proportional hazards models adjusted for age, race/ethnicity, study component, body mass index, physical activity, menopausal hormone therapy, smoking, diet quality, alcohol consumption, educational attainment, and neighborhood socioeconomic status, we estimated the relative risk of incident AF in association with each pollutant. RESULTS: A total of 16,348 incident AF cases were observed over 660,236 person-years of follow-up. Most exposure–response associations were non-linear. NO2 was associated with risk of AF in multivariable adjusted models [Hazard Ratio ðHRÞ = 1:18; 95% confidence interval (CI): 1.13, 1.24, comparing the top to bottom quartile, p-for-trend = < 0:0001]. Women living closer to roadways were at higher risk of AF (e.g., HR = 1:07; 95% CI: 1.01, 1.13 for living within 50 m of A3 roads, compared with ≥1,000 m, p-for-trend = 0:02), but we did not observe adverse associations with exposures to PM10, PM2:5, or SO2 . There were adverse associations with PM10 (top quartile HR = 1:10; 95% CI: 1.05, 1.16, p-for-trend = &lt; 0:0001) and PM2:5 (top quartile HR = 1:09; 95% CI: 1.03, 1.14, p-for-trend = 0:002) in sensitivity models adjusting for census region. DISCUSSION: In this study of postmenopausal women, NO2 and distance to road were consistently associated with higher risk of AF. https://doi.org/10.1289/EHP7683

BAs and boride III-V alloys

Boron arsenide, the typically-ignored member of the III-V arsenide series BAs-AlAs-GaAs-InAs is found to resemble silicon electronically: its Gamma conduction band minimum is p-like (Gamma_15), not s-like (Gamma_1c), it has an X_1c-like indirect band gap, and its bond charge is distributed almost equally on the two atoms in the unit cell, exhibiting nearly perfect covalency. The reasons for these are tracked down to the anomalously low atomic p orbital energy in the boron and to the unusually strong s-s repulsion in BAs relative to most other III-V compounds. We find unexpected valence band offsets of BAs with respect to GaAs and AlAs. The valence band maximum (VBM) of BAs is significantly higher than that of AlAs, despite the much smaller bond length of BAs, and the VBM of GaAs is only slightly higher than in BAs. These effects result from the unusually strong mixing of the cation and anion states at the VBM. For the BAs-GaAs alloys, we find (i) a relatively small (~3.5 eV) and composition-independent band gap bowing. This means that while addition of small amounts of nitrogen to GaAs lowers the gap, addition of small amounts of boron to GaAs raises the gap (ii) boron ``semi-localized'' states in the conduction band (similar to those in GaN-GaAs alloys), and (iii) bulk mixing enthalpies which are smaller than in GaN-GaAs alloys. The unique features of boride III-V alloys offer new opportunities in band gap engineering.Comment: 18 pages, 14 figures, 6 tables, 61 references. Accepted for publication in Phys. Rev. B. Scheduled to appear Oct. 15 200

Determination of the physical environment within the Chlamydia trachomatis inclusion using ion-selective ratiometric probes

Chlamydia trachomatis is an obligate intracellular bacterium with a biphasic life cycle that takes place entirely within a membrane-bound vacuole termed an inclusion. The chlamydial inclusion is non-fusogenic with endosomal or lysosomal compartments but intersects a pathway involved in transport of sphingomyelin from the Golgi apparatus to the plasma membrane. The physical conditions within the mature chlamydial inclusion are unknown. We used ratiometric imaging with membrane-permeant, ion-selective fluorescent dyes for microanalyis of the physical environment within the inclusion. Determination of H + , Na + , K + and Ca 2 + concentrations using CFDA (carboxy fluorescein diacetate) or BCECF-AM (2 ′ ,7 ′ -bis (2-carboxyethyl)-5,6-carboxyfluorescein acetoxymethyl ester, SBFI-AM, PBFI-AM and fura-PE3-acetomethoxyester (Fura-PE3-AM), respectively, indicated that all ions assayed within the lumenal space of the inclusion approximated the concentrations within the cytoplasm. Stimulation of purinergic receptors by addition of extracellular ATP triggered a dynamic Ca 2 + response that occurred simultaneously within the cytoplasm and interior of the inclusion. The chlamydial inclusion thus appears to be freely permeable to cytoplasmic ions. These results have implications for nutrient acquisition by chlamydiae and may contribute to the non-fusogenicity of the inclusion with endocytic compartments.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72253/1/j.1462-5822.2002.00191.x.pd