Itinerant ferromagnetism and intrinsic anomalous Hall effect in amorphous iron-germanium

The amorphous iron-germanium system (a-FexGe1-x) lacks long-range structural order and hence lacks a meaningful Brillouin zone. The magnetization of a-FexGe1-x is well explained by the Stoner model for Fe concentrations x above the onset of magnetic order around x=0.4, indicating that the local order of the amorphous structure preserves the spin-split density of states of the Fe-3d states sufficiently to polarize the electronic structure despite k being a bad quantum number. Measurements reveal an enhanced anomalous Hall resistivity ρxyAH relative to crystalline FeGe; this ρxyAH is compared to density-functional theory calculations of the anomalous Hall conductivity to resolve its underlying mechanisms. The intrinsic mechanism, typically understood as the Berry curvature integrated over occupied k states but shown here to be equivalent to the density of curvature integrated over occupied energies in aperiodic materials, dominates the anomalous Hall conductivity of a-FexGe1-x (0.38≤x≤0.61). The density of curvature is the sum of spin-orbit correlations of local orbital states and can hence be calculated with no reference to k space. This result and the accompanying Stoner-like model for the intrinsic anomalous Hall conductivity establish a unified understanding of the underlying physics of the anomalous Hall effect in both crystalline and disordered systems

Impact of massive neutrinos on the Higgs self-coupling and electroweak vacuum stability

The presence of right-handed neutrinos in the type I seesaw mechanism may lead to significant corrections to the RG evolution of the Higgs self-coupling. Compared to the Standard Model case, the Higgs mass window can become narrower, and the cutoff scale become lower. Naively, these effects decrease with decreasing right-handed neutrino mass. However, we point out that the unknown Dirac Yukawa matrix may impact the vacuum stability constraints even in the low scale seesaw case not far away from the electroweak scale, hence much below the canonical seesaw scale of 10^15 GeV. This includes situations in which production of right-handed neutrinos at colliders is possible. We illustrate this within a particular parametrization of the Dirac Yukawas and with explicit low scale seesaw models. We also note the effect of massive neutrinos on the top quark Yukawa coupling, whose high energy value can be increased with respect to the Standard Model case.Comment: 17 pages, 7 figures, minor revisions, version to appear in JHE

EWPD Constraints on Flavor Symmetric Vector Fields

Electroweak precision data constraints on flavor symmetric vector fields are determined. The flavor multiplets of spin one that we examine are the complete set of fields that couple to quark bi-linears at tree level while not initially breaking the quark global flavor symmetry group. Flavor safe vector masses proximate to, and in some cases below, the electroweak symmetry breaking scale are found to be allowed. Many of these fields provide a flavor safe mechanism to explain the t tbar forward backward anomaly, and can simultaneously significantly raise the allowed values of the Standard Model Higgs mass consistent with electroweak precision data.Comment: Matches version published in JHE

Functional diversity of marine ecosystems after the Late Permian mass extinction event

Article can be accessed from http://www.nature.com/ngeo/journal/v7/n3/full/ngeo2079.htmlThe Late Permian mass extinction event was the most severe such crisis of the past 500 million years and occurred during an episode of global warming. It is assumed to have had significant ecological impact, but its effects on marine ecosystem functioning are unknown and the patterns of marine recovery are debated. We analysed the fossil occurrences of all known Permian-Triassic benthic marine genera and assigned each to a functional group based on their inferred life habit. We show that despite the selective extinction of 62-74% of marine genera there was no significant loss of functional diversity at the global scale, and only one novel mode of life originated in the extinction aftermath. Early Triassic marine ecosystems were not as ecologically depauperate as widely assumed, which explains the absence of a Cambrian-style Triassic radiation in higher taxa. Functional diversity was, however, significantly reduced in particular regions and habitats, such as tropical reefs, and at these scales recovery varied spatially and temporally, probably driven by migration of surviving groups. Marine ecosystems did not return to their pre-extinction state, however, and radiation of previously subordinate groups such as motile, epifaunal grazers led to greater functional evenness by the Middle Triassic

HUWE1 cooperates with RAS activation to control leukemia cell proliferation and human hematopoietic stem cells differentiation fate

Acute myeloid leukemia (AML) is a poor prognosis hematopoietic malignance characterized by abnormal proliferation and differentiation of hematopoietic stem cells (HSCs). Although advances in treatment have greatly improved survival rates in young patients, in the elderly population, ~70% of patients present poor prognosis. A pan-cancer analysis on the TCGA cohort showed that AML has the second higher HUWE1 expression in tumor samples among all cancer types. In addition, pathway enrichment analysis pointed to RAS signaling cascade as one of the most important pathways associated to HUWE1 expression in this particular AML cohort. In silico analysis for biological processes enrichment also revealed that HUWE1 expression is correlated with 13 genes involved in myeloid differentiation. Therefore, to understand the role of HUWE1 in human hematopoietic stem and progenitor cells (HSPC) we constitutively expressed KRASG12V oncogene concomitantly to HUWE1 knockdown in stromal co-cultures. The results showed that, in the context of KRASG12V, HUWE1 significantly reduces cell cumulative growth and changes myeloid differentiation profile of HSPCs. Overall, these observations suggest that HUWE1 might contribute to leukemic cell proliferation and impact myeloid differentiation of human HSCs, thus providing new venues for RAS-driven leukemia targeted therapy approach

Molecular and Clinical Findings in Patients With Knobloch Syndrome

IMPORTANCE: Knobloch syndrome is a rare, recessively inherited disorder classically characterized by high myopia, retinal detachment, and occipital encephalocele, but it is now known to have an increasingly variable phenotype. There is a lack of reported electrophysiologic data, and some key clinical features have yet to be described. OBJECTIVE: To expand on current clinical, electrophysiologic, and molecular genetic findings in Knobloch syndrome. DESIGN, SETTING AND PARTICIPANTS: Twelve patients from 7 families underwent full ophthalmic examination and retinal imaging. Further investigations included electroretinography and neuroradiologic imaging. Bidirectional Sanger sequencing of COL18A1 was performed with segregation on available relatives. The study was conducted from July 4, 2013, to October 5, 2015. Data analysis was performed from May 20, 2014, to November 3, 2015. MAIN OUTCOMES AND MEASURES: Results of ophthalmic and neuroradiologic assessment and sequence analysis of COL18A1. RESULTS: Of the 12 patients (6 males; mean age at last review, 16 years [range, 2-38 years]), all had high myopia in at least 1 eye and severely reduced vision. A sibling pair had unilateral high myopia in their right eyes and near emmetropia in their left eyes from infancy. Anterior segment abnormalities included absent iris crypts, iris transillumination, lens subluxation, and cataract. Two patients with iris transillumination had glaucoma. Fundus characteristics included abnormal collapsed vitreous, macular atrophy, and a tesselated fundus. Five patients had previous retinal detachment. Electroretinography revealed a cone-rod pattern of dysfunction in 8 patients, was severely reduced or undetectable in 2 patients, and demonstrated cone-rod dysfunction in 1 eye with undetectable responses in the other eye in 2 patients. Radiologic imaging demonstrated occipital encephalocele or meningocele in 3 patients, occipital skull defects in 4 patients, minor occipital changes in 2 patients, and no abnormalities in 2 patients. Cutaneous scalp changes were present in 5 patients. Systemic associations were identified in 8 patients, including learning difficulties, epilepsy, and congenital renal abnormalities. Biallelic mutations including 2 likely novel mutations in COL18A1, were identified in 6 families that were consistent with autosomal recessive inheritance with a single mutation identified in a family with 2 affected children. CONCLUSIONS AND RELEVANCE: This report describes new features in patients with Knobloch syndrome, including pigment dispersion syndrome and glaucoma as well as cone-rod dysfunction on electroretinography. Two patients had normal neuroradiologic findings, emphasizing that some affected individuals have isolated ocular disease. Awareness of the ocular phenotype may aid early diagnosis, appropriate genetic counseling, and monitoring for potential complications

Fifteen-Year Population Attributable Fractions and Causal Pies of Risk Factors for Newly Developed Hepatocellular Carcinomas in 11,801 Men in Taiwan

Development of hepatocellular carcinoma (HCC) is a multi-factorial process. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are important risk factors of HCC. Host factors, such as alcohol drinking, may also play a role. This study aims to provide a synthesis view on the development of HCC by examining multiple risk factors jointly and collectively. Causal-pie modeling technique was applied to analyze a cohort of 11,801 male residents (followed up for 15 years) in Taiwan, during which a total of 298 incident HCC cases were ascertained. The rate ratios adjusted by age were further modeled by an additive Poisson regression. Population attributable fractions (PAFs) and causal-pie weights (CPWs) were calculated. A PAF indicates the magnitude of case-load reduction under a particular intervention scenario, whereas a CPW for a particular class of causal pies represents the proportion of HCC cases attributable to that class. Using PAF we observed a chance to reduce around 60% HCC risk moving from no HBV-related intervention to the total elimination of the virus. An additional ∼15% (or ∼5%) reduction can be expected, if the HBV-related intervention is coupled with an HCV-related intervention (or an anti-drinking campaign). Eight classes of causal pies were found to be significant, including four dose-response classes of HBV (total CPW=52.7%), one independent-effect class of HCV (CPW=14.4%), one HBV-alcohol interaction class (CPW=4.2%), one HBV-HCV interaction class (CPW=1.7%), and one all-unknown class (CPW=27.0%). Causal-pie modeling for HCC helps clarify the relative importance of each viral and host factor, as well as their interactions

Evo-devo of human adolescence: beyond disease models of early puberty

Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research

Increased levels of RNA oxidation enhance the reversion frequency in aging pro-apoptotic yeast mutants

Despite recent advances in understanding the complexity of RNA processes, regulation of the metabolism of oxidized cellular RNAs and the mechanisms through which oxidized ribonucleotides affect mRNA translation, and consequently cell viability, are not well characterized. We show here that the level of oxidized RNAs is markedly increased in a yeast decapping Kllsm4Δ1 mutant, which accumulates mRNAs, ages much faster that the wild type strain and undergoes regulated-cell-death. We also found that in Kllsm4Δ1 cells the mutation rate increases during chronological life span indicating that the capacity to han- dle oxidized RNAs in yeast declines with aging. Lowering intracellular ROS levels by antioxidants recovers the wild- type phenotype of mutant cells, including reduced amount of oxidized RNAs and lower mutation rate. Since mRNA oxidation was reported to occur in different neurodegen- erative diseases, decapping-deficient cells may represent a useful tool for deciphering molecular mechanisms of cell response to such conditions, providing new insights into RNA modification-based pathogenesis