Non-adiabatic quantum effects from a Standard Model time-dependent Higgs vev

We consider the time-dependence of the Higgs vacuum expectation value (vev) given by the dynamics of the Standard Model and study the non-adiabatic production of both bosons and fermions, which is intrinsically non-perturbative. In the Hartree approximation, we analyse the general expressions that describe the dissipative dynamics due to the back-reaction of the produced particles. In particular, we solve numerically some relevant cases for the Standard Model phenomenology in the regime of relatively small oscillations of the Higgs vev.Comment: 35 pages, 15 figures and 2 table

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

A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate multiple functional annotations. In non-gene-centric analysis, STAARpipeline uses SCANG-STAAR to incorporate dynamic window sizes and multiple functional annotations. We apply STAARpipeline to identify noncoding RV sets associated with four lipid traits in 21,015 discovery samples from the Trans-Omics for Precision Medicine (TOPMed) program and replicate several of them in an additional 9,123 TOPMed samples. We also analyze five non-lipid TOPMed traits

New Opportunities And Hazards Brought By Humans To The Island Habitat Of The Skink Euprepis Atlanticus

[No abstract available]1003033Bennett, A.F., Gorman, G.C., Population density, thermal relations, and energetics of a tropical insular lizard community (1979) Oecologia, 42, pp. 339-358Carleton, M.D., Olson, S.L., Amerigo Vespucci and the rat of Fernando de Noronha: A new genus and species of Rodentia (Muridae: Sigmodontinae) from a volcanic island off Brazil's continental shelf (1999) Am. Mus. Novit, 3256, pp. 1-59Mausfeld, P., Schmitz, A., Bohme, W., Misof, B., Vrcibradic, D., Rocha, C.F.D., Phylogenetic affinities of Mabuya atlantica Schmidt, 1945, endemic to the Atlantic Ocean archipelago of Fernando de Noronha (Brazil): Necessity of partitioning the genus Mabuya Fitzinger, 1826 (Scincidae: Lygosominae) (2002) Zool. Anz, 241, pp. 281-293Mausfeld, P., Vrcibradic, D., On the nomenclature of the skink (Mabuya) endemic to the western Atlantic archipelago of Fernando de Noronha (2002) Brazil. J. Herpetol, 36, pp. 292-295Olesen, J.M., Valido, A., Lizards as pollinators and seed dispersers: An island phenomenon (2003) Trends Ecol. Evol, 18, pp. 177-181Pianka, E.R., The structure of lizard communities (1973) Ann. Rev. Ecol. Syst, 4, pp. 53-74Pianka, E.R., Vitt, L.J., (2003) Lizards: Windows to the evolution of diversity, , Berkeley: University of California Press, 347 ppRobinson, P.L., Cuningham, A.B., Comparative diet of two Namib Desert sand lizards (Lacertidae) (1978) Madoqua, 11, pp. 411-453Sazima, I., Sazima, C., Sazima, M., Little dragons prefer flowers to maidens: A lizard that laps nectar and pollinates trees (2005) Biota Neotrop, 5, pp. 1-8Schoener, T.W., The Anolis lizards of Bimini: Resource partitioning in a complex fauna (1968) Ecology, 49, pp. 704-726Schoener, T.W., Toft, C.A., Spider populations: Extraordinarily high densities on islands without top predators (1983) Science, 219, pp. 1353-1355Silva-Jr, J.M., Péres-Jr, A.K., Sazima, I., Euprepis atlanticus (Noronha skink). Predation (2005) Herpetol. Rev, 36, pp. 62-63Vitt, L.J., Pianka, E.R., Deep history impacts present day ecology and biodiversity (2005) Proc. Natl. Acad. Sci, 102, pp. 7877-7881Whiting, A.S., Sites-Jr, J.W., Pellegrino, K.C.M., Rodrigues, M.T., Comparing alignment methods for inferring the history of the new world lizard genus Mabuya (Squamata: Scincidae) (2005) Molec. Phylogen. Evol, 38, pp. 719-73

Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction

Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.Ron Do, Nathan O. Stitziel, Hong-Hee Won, Anders Berg Jørgensen, Stefano Duga, Pier Angelica Merlini ... et al

Whole-Exome Sequencing Identifies Loci Associated with Blood Cell Traits and Reveals a Role for Alternative GFI1B Splice Variants in Human Hematopoiesis

Clinical epidemiolog

Loss-of-function mutations in APOC3, triglycerides, and coronary disease.

BACKGROUND: Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. METHODS: We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. RESULTS: An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G\u2192A and IVS3+1G\u2192T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1 710(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P=8 710(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P=4 710(-6)). CONCLUSIONS: Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease

Rare and low-frequency coding variants alter human adult height

Pathophysiology, epidemiology and therapy of agein

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of