Rapid Evolution of BRCA1 and BRCA2 in Humans and Other Primates

The maintenance of chromosomal integrity is an essential task of every living organism and cellular repair mechanisms exist to guard against insults to DNA. Given the importance of this process, it is expected that DNA repair proteins would be evolutionarily conserved, exhibiting very minimal sequence change over time. However, BRCA1, an essential gene involved in DNA repair, has been reported to be evolving rapidly despite the fact that many protein-altering mutations within this gene convey a significantly elevated risk for breast and ovarian cancers. Results: To obtain a deeper understanding of the evolutionary trajectory of BRCA1, we analyzed complete BRCA1 gene sequences from 23 primate species. We show that specific amino acid sites have experienced repeated selection for amino acid replacement over primate evolution. This selection has been focused specifically on humans and our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). After examining BRCA1 polymorphisms in 7 bonobo, 44 chimpanzee, and 44 rhesus macaque (Macaca mulatta) individuals, we find considerable variation within each of these species and evidence for recent selection in chimpanzee populations. Finally, we also sequenced and analyzed BRCA2 from 24 primate species and find that this gene has also evolved under positive selection. Conclusions: While mutations leading to truncated forms of BRCA1 are clearly linked to cancer phenotypes in humans, there is also an underlying selective pressure in favor of amino acid-altering substitutions in this gene. A hypothesis where viruses are the drivers of this natural selection is discussed.National Institutes of Health R01-GM-093086, 8U42OD011197-13National Science Foundation BCS-07115972Burroughs Wellcome FundMolecular Bioscience

Neutrino Interactions in Hot and Dense Matter

We study the charged and neutral current weak interaction rates relevant for the determination of neutrino opacities in dense matter found in supernovae and neutron stars. We establish an efficient formalism for calculating differential cross sections and mean free paths for interacting, asymmetric nuclear matter at arbitrary degeneracy. The formalism is valid for both charged and neutral current reactions. Strong interaction corrections are incorporated through the in-medium single particle energies at the relevant density and temperature. The effects of strong interactions on the weak interaction rates are investigated using both potential and effective field-theoretical models of matter. We investigate the relative importance of charged and neutral currents for different astrophysical situations, and also examine the influence of strangeness-bearing hyperons. Our findings show that the mean free paths are significantly altered by the effects of strong interactions and the multi-component nature of dense matter. The opacities are then discussed in the context of the evolution of the core of a protoneutron star.Comment: 41 pages, 25 figure

How to identify a Strange Star

Contrary to young neutron stars, young strange stars are not subject to the r-mode instability which slows rapidly rotating, hot neutron stars to rotation periods near 10 ms via gravitational wave emission. Young millisecond pulsars are therefore likely to be strange stars rather than neutron stars, or at least to contain significant quantities of quark matter in the interior.Comment: 4 pages, 1 figur

Massive migration from the steppe is a source for Indo-European languages in Europe

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost four hundred thousand polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of western and far eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ~8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary, and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By ~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred throughout much of Europe, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ~3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for the theory of a steppe origin of at least some of the Indo-European languages of Europe

Neutrino-Nucleon Interactions in Magnetized Neutron-Star Matter: The Effects of Parity Violation

We study neutrino-nucleon scattering and absorption in a dense, magnetized nuclear medium. These are the most important sources of neutrino opacity governing the cooling of a proto-neutron star in the first tens of seconds after its formation. Because the weak interaction is parity violating, the absorption and scattering cross-sections depend asymmetrically on the directions of the neutrino momenta with respect to the magnetic field. We develop the moment formalism of neutrino transport in the presence of such asymmetric opacities and derive explicit expressions for the neutrino flux and other angular moments of the Boltzmann transport equation. For a given neutrino species, there is a drift flux of neutrinos along the magnetic field in addition to the usual diffusive flux. This drift flux depends on the deviation of the neutrino distribution function from thermal equilibrium. Hence, despite the fact that the neutrino cross-sections are asymmetric throughout the star, asymmetric neutrino flux can be generated only in the outer region of the proto-neutron star where the neutrino distribution deviates significantly from thermal equilibrium. In addition to the asymmetric absorption opacity arising from nucleon polarization, we find the contribution of the electron (or positron) ground state Landau level. For neutrinos of energy less than a few times the temperature, this is the dominant source of asymmetric opacity. Lastly, we discuss the implication of our result to the origin of pulsar kicks: in order to generate kick velocity of a few hundred km/s from asymmetric neutrino emission using the parity violation effect, the proto-neutron star must have a dipole magnetic field of at least $10^{15}-10^{16}$ G.Comment: 35 pages, no figures, submitted to Phys.Rev.

Physics and Astrophysics of Strange Quark Matter

3-flavor quark matter (strange quark matter; SQM) can be stable or metastable for a wide range of strong interaction parameters. If so, SQM can play an important role in cosmology, neutron stars, cosmic ray physics, and relativistic heavy-ion collisions. As an example of the intimate connections between astrophysics and heavy-ion collision physics, this Chapter gives an overview of the physical properties of SQM in bulk and of small-baryon number strangelets; discusses the possible formation, destruction, and implications of lumps of SQM (quark nuggets) in the early Universe; and describes the structure and signature of strange stars, as well as formation and detection of strangelets in cosmic rays. It is concluded, that astrophysical and laboratory searches are complementary in many respects, and that both should be pursued to test the intriguing possibility of a strange ground state for hadronic matter, and (more generally) to improve our knowledge of the strong interactions.Comment: 45 pages incl. figures. To appear in "Hadrons in Dense Matter and Hadrosynthesis", Lecture Notes in Physics, Springer Verlag (ed. J.Cleymans

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Spin-Isospin Structure and Pion Condensation in Nucleon Matter

We report variational calculations of symmetric nuclear matter and pure neutron matter, using the new Argonne v18 two-nucleon and Urbana IX three-nucleon interactions. At the equilibrium density of 0.16 fm^-3 the two-nucleon densities in symmetric nuclear matter are found to exhibit a short-range spin-isospin structure similar to that found in light nuclei. We also find that both symmetric nuclear matter and pure neutron matter undergo transitions to phases with pion condensation at densities of 0.32 fm^-3 and 0.2 fm^-3, respectively. Neither transtion occurs with the Urbana v14 two-nucleon interaction, while only the transition in neutron matter occurs with the Argonne v14 two-nucleon interaction. The three-nucleon interaction is required for the transition to occur in symmetric nuclear matter, whereas the the transition in pure neutron matter occurs even in its absence. The behavior of the isovector spin-longitudinal response and the pion excess in the vicinity of the transition, and the model dependence of the transition are discussed.Comment: 44 pages RevTeX, 15 postscript figures. Minor modifications to original postin

Evidence for Restriction of Ancient Primate Gammaretroviruses by APOBEC3 but Not TRIM5α Proteins

Because of evolutionary pressures imposed through episodic colonization by retroviruses, many mammals express factors, such as TRIM5α and APOBEC3 proteins, that directly restrict retroviral replication. TRIM5 and APOBEC restriction factors are most often studied in the context of modern primate lentiviruses, but it is likely that ancient retroviruses imposed the selective pressure that is evident in primate TRIM5 and APOBEC3 genes. Moreover, these antiretroviral factors have been shown to act against a variety of retroviruses, including gammaretroviruses. Endogenous retroviruses can provide a ‘fossil record’ of extinct retroviruses and perhaps evidence of ancient TRIM5 and APOBEC3 antiviral activity. Here, we investigate whether TRIM5 and APOBEC3 proteins restricted the replication of two groups of gammaretroviruses that were endogenized in the past few million years. These endogenous retroviruses appear quite widespread in the genomes of old world primates but failed to colonize the human germline. Our analyses suggest that TRIM5α proteins did not pose a major barrier to the cross-species transmission of these two families of gammaretroviruses, and did not contribute to their extinction. However, we uncovered extensive evidence for inactivation of ancient gammaretroviruses through the action of APOBEC3 cytidine deaminases. Interestingly, the identities of the cytidine deaminases responsible for inactivation appear to have varied in both a virus and host species–dependent manner. Overall, sequence analyses and reconstitution of ancient retroviruses from remnants that have been preserved in the genomes of modern organisms offer the opportunity to probe and potentially explain the evolutionary history of host defenses against retroviruses

Search for Top Squark Pair Production in the Dielectron Channel

This report describes the first search for top squark pair production in the channel stop_1 stopbar_1 -> b bbar chargino_1 chargino_1 -> ee+jets+MEt using 74.9 +- 8.9 pb^-1 of data collected using the D0 detector. A 95% confidence level upper limit on sigma*B is presented. The limit is above the theoretical expectation for sigma*B for this process, but does show the sensitivity of the current D0 data set to a particular topology for new physics.Comment: Five pages, including three figures, submitted to PRD Brief Report