Autistic Disorders and Schizophrenia: Related or Remote? An Anatomical Likelihood Estimation

Shared genetic and environmental risk factors have been identified for autistic spectrum disorders (ASD) and schizophrenia. Social interaction, communication, emotion processing, sensorimotor gating and executive function are disrupted in both, stimulating debate about whether these are related conditions. Brain imaging studies constitute an informative and expanding resource to determine whether brain structural phenotype of these disorders is distinct or overlapping. We aimed to synthesize existing datasets characterizing ASD and schizophrenia within a common framework, to quantify their structural similarities. In a novel modification of Anatomical Likelihood Estimation (ALE), 313 foci were extracted from 25 voxel-based studies comprising 660 participants (308 ASD, 352 first-episode schizophrenia) and 801 controls. The results revealed that, compared to controls, lower grey matter volumes within limbic-striato-thalamic circuitry were common to ASD and schizophrenia. Unique features of each disorder included lower grey matter volume in amygdala, caudate, frontal and medial gyrus for schizophrenia and putamen for autism. Thus, in terms of brain volumetrics, ASD and schizophrenia have a clear degree of overlap that may reflect shared etiological mechanisms. However, the distinctive neuroanatomy also mapped in each condition raises the question about how this is arrived in the context of common etiological pressures

Characterization of a genetic and antigenic variant of avian paramyxovirus 6 isolated from a migratory wild bird, the red-necked stint (Calidris ruficollis)

A hemagglutinating virus (8KS0813) was isolated from a red-necked stint. Hemagglutination inhibition and neutralization tests indicated that 8KS0813 was antigenically related to a prototype strain, APMV-6/duck/Hong Kong/18/199/77, but with an 8- and 16-fold difference, respectively, in their titers. The full genome sequence of 8KS0813 showed 98.6 % nucleotide sequence identity to that of APMV-6/duck/Italy/4524-2/07, which has been reported to belong to an APMV-6 subgroup, and showed less similarity to that of the prototype strain (70.6 % similarity). The growth of 8KS0813 and the prototype strain in four different cell cultures was greatly enhanced by adding trypsin. Interestingly, this virus induced syncytia only in Vero cells. 8KS0813 was identified as APMV-6/red-necked stint/Japan/8KS0813/08, but it is antigenically and genetically distinguishable from the prototype strain, suggesting that variant APMV-6 is circulating in migratory birds.Program of Founding Research Centers for Emerging and Reemerging Infectious DiseasesJapan. Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Exploratory Research (19659115))National Institute of Allergy and Infectious Diseases (U.S.) (NIAID contracts HHSN266200700009C and HHSN266200700007C

Association between abdominal aortic calcification, bone mineral density and fracture in older women

Although a relationship between vascular disease and osteoporosis has been recognized, its clinical importance for fracture risk evaluation remains uncertain. Abdominal aortic calcification (AAC), a recognized measure of vascular disease detected on single‐energy images performed for vertebral fracture assessment, may also identify increased osteoporosis risk. In a prospective 10‐year study of 1,024 older predominantly Caucasian women (mean age 75.0±2.6 years) from the Perth Longitudinal Study of Aging cohort we evaluated the association between AAC, skeletal structure and fractures. AAC and spine fracture were assessed at the time of hip densitometry and heel quantitative ultrasound. AAC was scored 0 to 24 (AAC24) and categorized into; low AAC (score 0 and 1, n=459), moderate AAC (score 2‐5, n=373) and severe AAC (score \u3e 6, n=192). Prevalent vertebral fractures were calculated using the Genant semi‐quantitative method. AAC24 scores were inversely related to hip bone mineral density (BMD) (rs=‐0.077, p=0.013) and heel broadband ultrasound attenuation (rs=‐0.074, p=0.020) and stiffness index (rs=‐0.073, p=0.022). In cross‐sectional analyses women with moderate to severe AAC were more likely to have prevalent fracture and LSI detected lumbar spine but not thoracic spine fractures (Mantel‐Haentzel test of trend p \u3c 0.05). For 10‐year incident clinical fractures and fracture‐related hospitalizations women with moderate to severe AAC (AAC24 score \u3e1) had increased fracture risk (HR 1.48 [1.15‐1.91], p=0.002; HR 1.46 [1.07‐1.99], p=0.019, respectively) compared to women with low AAC. This relationship remained significant after adjusting for age and hip BMD for clinical fractures (HR 1.40 [1.08‐1.81], p=0.010) but was attenuated for fracture‐related hospitalizations (HR 1.33 [0.98‐1.83], p=0.073). In conclusion, older women with more marked AAC are at higher risk of fracture, not completely captured by bone structural predictors. These findings further support the concept that vascular calcification and bone pathology may share similar mechanisms of causation that remain to be fully elucidated

Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells

Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6), and chromatin modifiers (Trim28/Eset/Atf7ip) are key determinants that establish provirus silencing. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs. ChIP-seq analysis demonstrates direct recruitment of Chaf1a and Sumo2 to ERVs. Chaf1a reinforces transcriptional repression via its interaction with members of the NuRD complex (Kdm1a, Hdac1/2) and Eset, while Sumo2 orchestrates the provirus repressive function of the canonical Zfp809/Trim28/Eset machinery by sumoylation of Trim28. Our study reports a genome-wide atlas of functional nodes that mediate proviral silencing in ESCs and illuminates the comprehensive, interconnected, and multi-layered genetic and epigenetic mechanisms by which ESCs repress retroviruses within the genome

Characterizing the Sensitivity of 40 GHz TES Bolometers for BICEP Array

The BICEP/Keck (BK) experiment aims to detect the imprint of primordial gravitational waves in the cosmic microwave background polarization, which would be direct evidence of the inflation theory. While the tensor-to-scalar ratio has been constrained to be r_(0.05) < 0.06 at 95% c.l., further improvements on this upper limit are hindered by polarized galactic foreground emissions and removal of gravitational lensing polarization. The 30/40 GHz receiver of the BICEP Array (BA) will deploy at the end of 2019 and will constrain the synchrotron foreground with unprecedented accuracy within the BK sky patch. We will show the design of the 30/40 GHz detectors and test results summarizing its performance. The low optical and atmospheric loading at these frequencies requires our TES detectors to have low saturation power in order to be photon noise dominated. To realize the low thermal conductivity required from a 250 mK base temperature, we developed new bolometer leg designs. We will present the relevant measured detector parameters: G, T_c, R_n, P_(sat), and spectral bands, and noise spectra. We achieved a per bolometer NEP including all noise components of 2.07×10⁻¹⁷ W/√Hz, including an anticipated photon noise level 1.54×10⁻¹⁷W/√Hz

Design and Performance of the First BICEP Array Receiver

Branches of cosmic inflationary models, such as slow-roll inflation, predict a background of primordial gravitational waves that imprints a unique odd-parity “B-mode” pattern in the Cosmic Microwave Background (CMB) at amplitudes that are within experimental reach. The BICEP/Keck (BK) experiment targets this primordial signature, the amplitude of which is parameterized by the tensor-to-scalar ratio r, by observing the polarized microwave sky through the exceptionally clean and stable atmosphere at the South Pole. B-mode measurements require an instrument with exquisite sensitivity, tight control of systematics, and wide frequency coverage to disentangle the primordial signal from the Galactic foregrounds. BICEP Array represents the most recent stage of the BK program and comprises four BICEP3-class receivers observing at 30/40, 95, 150 and 220/270 GHz. The 30/40 GHz receiver will be deployed at the South Pole during the 2019/2020 austral summer. After 3 full years of observations with 30,000+ detectors, BICEP Array will measure primordial gravitational waves to a precision σ(r) between 0.002 and 0.004, depending on foreground complexity and the degree of lensing removal. In this paper, we give an overview of the instrument, highlighting the design features in terms of cryogenics, magnetic shielding, detectors and readout architecture as well as reporting on the integration and tests that are ongoing with the first receiver at 30/40 GHz

Optical Design and Characterization of 40-GHz Detector and Module for the BICEP Array

Families of cosmic inflation models predict a primordial gravitational-wave background that imprints B-mode polarization pattern in the cosmic microwave background (CMB). High-sensitivity instruments with wide frequency coverage and well-controlled systematic errors are needed to constrain the faint B-mode amplitude. We have developed antenna-coupled transition edge sensor arrays for high-sensitivity polarized CMB observations over a wide range of millimeter-wave bands. BICEP array, the latest phase of the BICEP/Keck experiment series, is a multi-receiver experiment designed to search for inflationary B-mode polarization to a precision σ(r) between 0.002 and 0.004 after 3 full years of observations, depending on foreground complexity and the degree of lensing removal. We describe the electromagnetic design and measured performance of BICEP array’s low-frequency 40-GHz detector, their packaging in focal plane modules, and optical characterization including efficiency and beam matching between polarization pairs. We summarize the design and simulated optical performance, including an approach to improve the optical efficiency due to mismatch losses. We report the measured beam maps for a new broadband corrugation design to minimize beam differential ellipticity between polarization pairs caused by interactions with the module housing frame, which helps minimize polarized beam mismatch that converts CMB temperature to polarization (T→P) anisotropy in CMB maps

MRI Study of Minor Physical Anomaly in Childhood Autism Implicates Aberrant Neurodevelopment in Infancy

Background: MPAs (minor physical anomalies) frequently occur in neurodevelopmental disorders because both face and brain are derived from neuroectoderm in the first trimester. Conventionally, MPAs are measured by evaluation of external appearance. Using MRI can help overcome inherent observer bias, facilitate multi-centre data acquisition, and explore how MPAs relate to brain dysmorphology in the same individual. Optical MPAs exhibit a tightly synchronized trajectory through fetal, postnatal and adult life. As head size enlarges with age, inter-orbital distance increases, and is mostly completed before age 3 years. We hypothesized that optical MPAs might afford a retrospective 'window' to early neurodevelopment; specifically, inter-orbital distance increase may represent a biomarker for early brain dysmaturation in autism. Methods: We recruited 91 children aged 7-16; 36 with an autism spectrum disorder and 55 age- and gender-matched typically developing controls. All children had normal IQ. Inter-orbital distance was measured on T1-weighted MRI scans. This value was entered into a voxel-by-voxel linear regression analysis with grey matter segmented from a bimodal MRI data-set. Age and total brain tissue volume were entered as covariates. Results: Intra-class coefficient for measurement of the inter-orbital distance was 0.95. Inter-orbital distance was significantly increased in the autism group (p = 0.03, 2-tailed). The autism group showed a significant relationship between inter-orbital distance grey matter volume of bilateral amygdalae extending to the unci and inferior temporal poles. Conclusions: Greater inter-orbital distance in the autism group compared with healthy controls is consistent with infant head size expansion in autism. Inter-orbital distance positively correlated with volume of medial temporal lobe structures, suggesting a link to "social brain" dysmorphology in the autism group. We suggest these data support the role of optical MPAs as a "fossil record" of early aberrant neurodevelopment, and potential biomarker for brain dysmaturation in autism. © 2011 Cheung et al.published_or_final_versio