Linearized gravity on the Randall-Sundrum two-brane background with curvature terms in the action for the branes

We study gravitational perturbations in the Randall-Sundrum two-brane background with scalar-curvature terms in the action for the branes, allowing for positive as well as negative bulk gravitational constant. In the zero-mode approximation, we derive the linearized gravitational equations, which have the same form as in the original Randall-Sundrum model but with different expressions for the effective physical constants. We develop a generic method for finding tachyonic modes in the theory, which, in the model under consideration, may exist only if the bulk gravitational constant is negative. In this case, if both brane gravitational constants are nonzero, the theory contains one or two tachyonic mass eigenvalues in the gravitational sector. If one of the brane gravitational constants is set to zero, then either a single tachyonic mass eigenvalue is present or tachyonic modes are totally absent depending on the relation between the nonzero brane gravitational constant and brane separation. In the case of negative bulk gravitational constant, the massive gravitational modes have ghost-like character, while the massless gravitational mode is not a ghost in the case where tachyons are absent.Comment: 23 pages, revtex, published versio

Gravitational instability on the brane: the role of boundary conditions

An outstanding issue in braneworld theory concerns the setting up of proper boundary conditions for the brane-bulk system. Boundary conditions (BC's) employing regulatory branes or demanding that the bulk metric be nonsingular have yet to be implemented in full generality. In this paper, we take a different route and specify boundary conditions directly on the brane thereby arriving at a local and closed system of equations (on the brane). We consider a one-parameter family of boundary conditions involving the anisotropic stress of the projection of the bulk Weyl tensor on the brane and derive an exact system of equations describing scalar cosmological perturbations on a generic braneworld with induced gravity. Depending upon our choice of boundary conditions, perturbations on the brane either grow moderately (region of stability) or rapidly (instability). In the instability region, the evolution of perturbations usually depends upon the scale: small scale perturbations grow much more rapidly than those on larger scales. This instability is caused by a peculiar gravitational interaction between dark radiation and matter on the brane. Generalizing the boundary conditions obtained by Koyama and Maartens, we find for the Dvali-Gabadadze-Porrati model an instability, which leads to a dramatic scale-dependence of the evolution of density perturbations in matter and dark radiation. A different set of BC's, however, leads to a more moderate and scale-independent growth of perturbations. For the mimicry braneworld, which expands like LCDM, this class of BC's can lead to an earlier epoch of structure formation.Comment: 35 pages, 9 figures, an appendix and references added, version to be published in Classical and Quantum Gravit

Shaker-Related Potassium Channels in the Central Medial Nucleus of the Thalamus Are Important Molecular Targets for Arousal Suppression by Volatile General Anesthetics

The molecular targets and neural circuits that underlie general anesthesia are not fully elucidated. Here, we directly demonstrate that Kv1-family (Shaker-related) delayed rectifier K(+) channels in the central medial thalamic nucleus (CMT) are important targets for volatile anesthetics. The modulation of Kv1 channels by volatiles is network specific as microinfusion of ShK, a potent inhibitor of Kv1.1, Kv1.3, and Kv1.6 channels, into the CMT awakened sevoflurane-anesthetized rodents. In heterologous expression systems, sevoflurane, isoflurane, and desflurane at subsurgical concentrations potentiated delayed rectifier Kv1 channels at low depolarizing potentials. In mouse thalamic brain slices, sevoflurane inhibited firing frequency and delayed the onset of action potentials in CMT neurons, and ShK-186, a Kv1.3-selective inhibitor, prevented these effects. Our findings demonstrate the exquisite sensitivity of delayed rectifier Kv1 channels to modulation by volatile anesthetics and highlight an arousal suppressing role of Kv1 channels in CMT neurons during the process of anesthesia

Energizing Star Formation: The Cosmic Ray Ionization Rate in NGC 253 Derived From ALCHEMI Measurements of H3_3O+^+ and SO

The cosmic ray ionization rate (CRIR) is a key parameter in understanding the physical and chemical processes in the interstellar medium. Cosmic rays are a significant source of energy in star formation regions, which impacts the physical and chemical processes which drive the formation of stars. Previous studies of the circum-molecular zone (CMZ) of the starburst galaxy NGC 253 have found evidence for a high CRIR value; $10^3-10^6$ times the average cosmic ray ionization rate within the Milky Way. This is a broad constraint and one goal of this study is to determine this value with much higher precision. We exploit ALMA observations towards the central molecular zone of NGC 253 to measure the CRIR. We first demonstrate that the abundance ratio of H$_3$O$^+$ and SO is strongly sensitive to the CRIR. We then combine chemical and radiative transfer models with nested sampling to infer the gas properties and CRIR of several star-forming regions in NGC 253 due to emission from their transitions. We find that each of the four regions modelled has a CRIR in the range $(1-80)\times10^{-14}$ s$^{-1}$ and that this result adequately fits the abundances of other species that are believed to be sensitive to cosmic rays including C$_2$H, HCO$^+$, HOC$^+$, and CO. From shock and PDR/XDR models, we further find that neither UV/X-ray driven nor shock dominated chemistry are a viable single alternative as none of these processes can adequately fit the abundances of all of these species.Comment: 24 pages, 15 figures, accepted for publication in Ap

Starburst Energy Feedback Seen through HCO+/HOC+Emission in NGC 253 from ALCHEMI

Molecular abundances are sensitive to the UV photon flux and cosmic-ray ionization rate. In starburst environments, the effects of high-energy photons and particles are expected to be stronger. We examine these astrochemical signatures through multiple transitions of HCO+ and its metastable isomer HOC+ in the center of the starburst galaxy NGC 253 using data from the Atacama Large Millimeter/submillimeter Array large program ALMA Comprehensive High-resolution Extragalactic Molecular inventory. The distribution of the HOC+(1-0) integrated intensity shows its association with "superbubbles,"cavities created either by supernovae or expanding H ii regions. The observed HCO+/HOC+ abundance ratios are ∼10-150, and the fractional abundance of HOC+ relative to H2 is ∼1.5 × 10-11-6 × 10-10, which implies that the HOC+ abundance in the center of NGC 253 is significantly higher than in quiescent spiral arm dark clouds in the Galaxy and the Galactic center clouds. Comparison with chemical models implies either an interstellar radiation field of G 0 ⪆ 103 if the maximum visual extinction is ⪆5, or a cosmic-ray ionization rate of ζ ⪆ 10-14 s-1 (3-4 orders of magnitude higher than that within clouds in the Galactic spiral arms) to reproduce the observed results. From the difference in formation routes of HOC+, we propose that a low-excitation line of HOC+ traces cosmic-ray dominated regions, while high-excitation lines trace photodissociation regions. Our results suggest that the interstellar medium in the center of NGC 253 is significantly affected by energy input from UV photons and cosmic rays, sources of energy feedback.N.H. acknowledges support from JSPS KAKENHI grant No. JP21K03634. K.S. has been supported by grants MOST 108-2112-M-001-015 and 109- 2112-M-001-020 from the Ministry of Science and Technology, Taiwan. Y.N. is supported by the NAOJ ALMA Scientific Research grant No. 2017-06B. V.M.R. and L.C. are funded by the Comunidad de Madrid through the Atracción de Talento Investigador (Doctores con experiencia) Grant (COOL: Cosmic Origins Of Life; 2019-T1/TIC-15379)

The SARS-CoV-2 Lambda variant exhibits enhanced infectivity and immune resistance

SARS-CoV-2ラムダ株のウイルス学的・免疫学的性状の解明. 京都大学プレスリリース. 2021-12-23.SARS-CoV-2 Lambda, a variant of interest, has spread in some South American countries; however, its virological features and evolutionary traits remain unknown. In this study, we use pseudoviruses and reveal that the spike protein of the Lambda variant is more infectious than that of other variants due to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies and further augments antibody-mediated enhancement of infection. Although this mutation generates a nascent N-linked glycosylation site, the additional N-linked glycan is dispensable for the virological property conferred by this mutation. Since the Lambda variant has dominantly spread according to the increasing frequency of the isolates harboring the RSYLTPGD246-253N mutation, our data suggest that the RSYLTPGD246-253N mutation is closely associated with the substantial spread of the Lambda variant in South America

A genome-wide association study of aging

AbstractHuman longevity and healthy aging show moderate heritability (20%–50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10−8). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10−5). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity

A genome-wide association study of aging

Human longevity and healthy aging show moderate heritability (20–50%). We conducted a meta-analysis of genome-wide association studies from nine studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for two outcomes: a) all-cause mortality and b) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10−8). We found fourteen independent SNPs that predicted risk of death, and eight SNPs that predicted event-free survival (p < 10−5). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer’s disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

AbstractBackgroundThe genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.MethodsWe analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.ResultsThe SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10–9).ConclusionsThis large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion