Inertial waves near corotation in 3D hydrodynamical disks

This paper concerns the interaction between non-axisymmetric inertial waves and their corotation resonances in a hydrodynamical disk. Inertial waves are of interest because they can localise in resonant cavities circumscribed by Lindblad radii, and as a consequence exhibit discrete oscillation frequencies that may be observed. It is often hypothesised that these trapped eigenmodes are affiliated with the poorly understood QPO phenomenon. We demonstrate that a large class of non-axisymmetric 3D inertial waves cannot manifest as trapped normal modes. This class includes any inertial wave whose resonant cavity contains a corotation singularity. Instead, these `singular' modes constitute a continuous spectrum and, as an ensemble, are convected with the flow, giving rise to shearing waves. Lastly, we present a simple demonstration of how the corotation singularity stabilizes three-dimensional perturbations in a slender torus.Comment: 17 pages, 5 figures. MNRAS accepted. V2 - Section 5.2 moved to appendix and errors remove

Class-specific restrictions define primase interactions with DNA template and replicative helicase

Bacterial primase is stimulated by replicative helicase to produce RNA primers that are essential for DNA replication. To identify mechanisms regulating primase activity, we characterized primase initiation specificity and interactions with the replicative helicase for gram-positive Firmicutes (Staphylococcus, Bacillus and Geobacillus) and gram-negative Proteobacteria (Escherichia, Yersinia and Pseudomonas). Contributions of the primase zinc-binding domain, RNA polymerase domain and helicase-binding domain on de novo primer synthesis were determined using mutated, truncated, chimeric and wild-type primases. Key residues in the β4 strand of the primase zinc-binding domain defined class-associated trinucleotide recognition and substitution of these amino acids transferred specificity across classes. A change in template recognition provided functional evidence for interaction in trans between the zinc-binding domain and RNA polymerase domain of two separate primases. Helicase binding to the primase C-terminal helicase-binding domain modulated RNA primer length in a species-specific manner and productive interactions paralleled genetic relatedness. Results demonstrated that primase template specificity is conserved within a bacterial class, whereas the primase–helicase interaction has co-evolved within each species

MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load.

Mutations in the m.13094T>C MT-ND5 gene have been previously described in three cases of Leigh Syndrome (LS). In this retrospective, international cohort study we identified 20 clinically affected individuals (13 families) and four asymptomatic carriers. Ten patients were deceased at the time of analysis (median age of death was 10years (range: 5·4months-37years, IQR=17·9years). Nine patients manifested with LS, one with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and one with Leber hereditary optic neuropathy. The remaining nine patients presented with either overlapping syndromes or isolated neurological symptoms. Mitochondrial respiratory chain activity analysis was normal in five out of ten muscle biopsies. We confirmed maternal inheritance in six families, and demonstrated marked variability in tissue segregation, and phenotypic expression at relatively low blood mutant loads. Neuropathological studies of two patients manifesting with LS/MELAS showed prominent capillary proliferation, microvacuolation and severe neuronal cell loss in the brainstem and cerebellum, with conspicuous absence of basal ganglia involvement. These findings suggest that whole mtDNA genome sequencing should be considered in patients with suspected mitochondrial disease presenting with complex neurological manifestations, which would identify over 300 known pathogenic variants including the m.13094T>C

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.publishedVersio

Cerebral microinfarcts: the invisible lesions

The association between small but still visible lacunar infarcts and cognitive decline has been established by multiple population-based radiological and pathological studies. Microscopic examination of brain sections reveals even smaller but substantially more numerous microinfarcts, the focus of the current review. These lesions often result from small vessel pathologies such as arteriolosclerosis or cerebral amyloid angiopathy. They typically go undetected in clinical-radiological correlation studies that rely on conventional structural MRI, though the largest acute microinfarcts may be detectable by diffusion-weighted imaging. Given their high numbers and widespread distribution, microinfarcts may directly disrupt important cognitive networks and thus account for some of the neurologic dysfunction seen in association with lesions visible on conventional MRI such as lacunar infarcts and white matter hyperintensities. Standardized neuropathological assessment criteria and development of non-invasive means of detection during life would be major steps towards understanding the causes and consequences of the otherwise macroscopically invisible microinfarct

Cerebral Amyloid Angiopathy: A Systematic Review

Cerebral amyloid angiopathy (CAA) is a disorder characterized by amyloid deposition in the walls of leptomeningeal and cortical arteries, arterioles, and less often capillaries and veins of the central nervous system. CAA occurs mostly as a sporadic condition in the elderly, its incidence associating with advancing age. All sporadic CAA cases are due to deposition of amyloid-β, originating from proteolytic cleavage of the Amyloid Precursor Protein. Hereditary forms of CAA are generally familial (and therefore rare in the general population), more severe and earlier in onset. CAA-related lobar intracerebral hemorrhage is the most well-studied clinical condition associated with brain amyloid deposition. Despite ever increasing understanding of CAA pathogenesis and availability of reliable clinical and diagnostic tools, preventive and therapeutic options remain very limited. Further research efforts are required in order to identify biological targets for novel CAA treatment strategies. We present a systematic review of existing evidence regarding the epidemiology, genetics, pathogenesis, diagnosis and clinical management of CAA

A Statistical Study of Threshold Rotation Rates for the Formation of Disks around Be Stars

This paper presents a detailed statistical determination of the equatorial rotation rates of classical Be stars. The rapid rotation of Be stars is likely to be linked to the ejection of gas that forms dense circumstellar disks. The physical origins of these disks are not understood, though it is generally believed that the ability to spin up matter into a Keplerian disk depends on how close the stellar rotation speed is to the critical speed at which the centrifugal force cancels gravity. There has been recent disagreement between the traditional idea that Be stars rotate between 50 and 80 percent of their critical speeds and new ideas (inspired by the tendency for gravity darkening to mask rapid rotation at the equator) that their rotation may be very nearly critical. This paper utilizes Monte Carlo forward modeling to simulate distributions of the projected rotation speed (v sin i), taking into account gravity darkening, limb darkening, and observational uncertainties. A chi-squared minimization procedure was used to find the distribution parameters that best reproduce observed v sin i distributions from R. Yudin's database. Early-type (O7e-B2e) Be stars were found to exhibit a roughly uniform spread of intrinsic rotation speed that extends from 40 to 60 percent up to 100 percent of critical. Late-type (B3e-A0e) Be stars exhibit progressively narrower ranges of rotation speed as the effective temperature decreases; the lower limit rises to reach critical rotation for the coolest Be stars. The derived lower limits on equatorial rotation speed represent conservative threshold rotation rates for the onset of the Be phenomenon. The significantly subcritical speeds found for early-type Be stars represent strong constraints on physical models of angular momentum deposition in Be star disks.Comment: 36 pages (AASTeX), 11 figures, Ap. J., in press (November 20, 2005