Autistic Traits and Brain Activation during Face-to-Face Conversations in Typically Developed Adults

BACKGROUND: Autism spectrum disorders (ASD) are characterized by impaired social interaction and communication, restricted interests, and repetitive behaviours. The severity of these characteristics is posited to lie on a continuum that extends into the general population. Brain substrates underlying ASD have been investigated through functional neuroimaging studies using functional magnetic resonance imaging (fMRI). However, fMRI has methodological constraints for studying brain mechanisms during social interactions (for example, noise, lying on a gantry during the procedure, etc.). In this study, we investigated whether variations in autism spectrum traits are associated with changes in patterns of brain activation in typically developed adults. We used near-infrared spectroscopy (NIRS), a recently developed functional neuroimaging technique that uses near-infrared light, to monitor brain activation in a natural setting that is suitable for studying brain functions during social interactions. METHODOLOGY: We monitored regional cerebral blood volume changes using a 52-channel NIRS apparatus over the prefrontal cortex (PFC) and superior temporal sulcus (STS), 2 areas implicated in social cognition and the pathology of ASD, in 28 typically developed participants (14 male and 14 female) during face-to-face conversations. This task was designed to resemble a realistic social situation. We examined the correlations of these changes with autistic traits assessed using the Autism-Spectrum Quotient (AQ). PRINCIPAL FINDINGS: Both the PFC and STS were significantly activated during face-to-face conversations. AQ scores were negatively correlated with regional cerebral blood volume increases in the left STS during face-to-face conversations, especially in males. CONCLUSIONS: Our results demonstrate successful monitoring of brain function during realistic social interactions by NIRS as well as lesser brain activation in the left STS during face-to-face conversations in typically developed participants with higher levels of autistic traits

Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end

This research was originally published in Journal of Biological Chemistry. Hiroyuki Akama, Misa Kanemaki, Masato Yoshimura, Tomitake Tsukihara, Tomoe Kashiwagi, Hiroshi Yoneyama, Shin-ichiro Narita, Atsushi Nakagawa and Taiji Nakae. Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end. Journal of Biological Chemistry. 2004; 279, 52816-52819. © the American Society for Biochemistry and Molecular Biology

Social cost of mining-related lead (Pb) pollution in Kabwe, Zambia, and potential remediation measures

Lead (Pb) pollution has been one of the major environmental problems of worldwide significance. It is a latent factor for several fatal illnesses, whereas the exposure to lead in early childhood causes a lifetime IQ loss. The social cost is the concept to aggregate various adverse effects in a single monetary unit, which is useful in describing the pollution problem and provides foundation for the design of interventions. However, the assessment of the social cost is scarce for developing countries. In this study, we focus on the lead pollution problem of a former mining town, Kabwe, Zambia, where mining wastes abandoned near residential areas has caused a critical pollution problem. We first investigated the social cost of lead pollution that future generations born in 2025–2049 would incur in their lifetime. As the channels of the social cost, we considered the lost income from the IQ loss and the lost lives from lead-related mortality. The results showed that the social cost would amount to 224–593 million USD (discounted to the present value). Our results can be considered conservative, lower bound estimates because we focused only on well-identified effects of lead, but the social cost was still substantial. Then we examined several engineering remediation measures. The results showed that the social cost can be reduced (the benefits of remediations) more than the costs of implementing remediation measures. This study is the first to investigate the social cost of mining-related lead pollution problem in developing countries. Our interdisciplinary approach utilises the micro-level economic, health and pollution data and integrates the techniques in economics, toxicology and engineering.publishedVersio

Downregulation of the Wnt antagonist Dkk2 links the loss of Sept4 and myofibroblastic transformation of hepatic stellate cells.

Sept4, a subunit of the septin cytoskeleton specifically expressed in quiescent hepatic stellate cells (HSCs), is downregulated through transdifferentiation to fibrogenic and contractile myofibroblastic cells. Since Sept4(-/-)mice are prone to liver fibrosis, we aimed to identify the unknown molecular network underlying liver fibrosis by probing the association between loss of Sept4 and accelerated transdifferentiation of HSCs

EMPRESS. XI. SDSS and JWST Search for Local and z~4-5 Extremely Metal-Poor Galaxies (EMPGs): Clustering and Chemical Properties of Local EMPGs

We search for local extremely metal-poor galaxies (EMPGs), selecting photometric candidates by broadband color excess and machine-learning techniques with the SDSS photometric data. After removing stellar contaminants by shallow spectroscopy with Seimei and Nayuta telescopes, we confirm that three candidates are EMPGs with 0.05--0.1 $Z_\odot$ by deep Magellan/MagE spectroscopy for faint {\sc[Oiii]}$\lambda$4363 lines. Using a statistical sample consisting of 105 spectroscopically-confirmed EMPGs taken from our study and the literature, we calculate cross-correlation function (CCF) of the EMPGs and all SDSS galaxies to quantify environments of EMPGs. Comparing another CCF of all SDSS galaxies and comparison SDSS galaxies in the same stellar mass range ($10^{7.0}-10^{8.4} M_\odot$), we find no significant ($>1\sigma$) difference between these two CCFs. We also compare mass-metallicity relations (MZRs) of the EMPGs and those of galaxies at $z\sim$ 0--4 with a steady chemical evolution model and find that the EMPG MZR is comparable with the model prediction on average. These clustering and chemical properties of EMPGs are explained by a scenario of stochastic metal-poor gas accretion on metal-rich galaxies showing metal-poor star formation. Extending the broadband color-excess technique to a high-$z$ EMPG search, we select 17 candidates of $z\sim$ 4--5 EMPGs with the deep ($\simeq30$ mag) near-infrared JWST/NIRCam images obtained by ERO and ERS programs. We find galaxy candidates with negligible {\sc[Oiii]}$\lambda\lambda$4959,5007 emission weaker than the local EMPGs and known high-$z$ galaxies, suggesting that some of these candidates may fall in 0--0.01 $Z_\odot$, which potentially break the lowest metallicity limit known to date

Dynamic Changes in Ultrastructure of the Primary Cilium in Migrating Neuroblasts in the Postnatal Brain

New neurons, referred to as neuroblasts, are continuously generated in the ventricular-subventricular zone of the brain throughout an animal's life. These neuroblasts are characterized by their unique potential for proliferation, formation of chain-like cell aggregates, and long-distance and high-speed migration through the rostral migratory stream (RMS) toward the olfactory bulb (OB), where they decelerate and differentiate into mature interneurons. The dynamic changes of ultrastructural features in postnatal-born neuroblasts during migration are not yet fully understood. Here we report the presence of a primary cilium, and its ultrastructural morphology and spatiotemporal dynamics, in migrating neuroblasts in the postnatal RMS and OB. The primary cilium was observed in migrating neuroblasts in the postnatal RMS and OB in male and female mice and zebrafish, and a male rhesus monkey. Inhibition of intraflagellar transport molecules in migrating neuroblasts impaired their ciliogenesis and rostral migration toward the OB. Serial section transmission electron microscopy revealed that each migrating neuroblast possesses either a pair of centrioles or a basal body with an immature or mature primary cilium. Using immunohistochemistry, live imaging, and serial block-face scanning electron microscopy, we demonstrate that the localization and orientation of the primary cilium are altered depending on the mitotic state, saltatory migration, and deceleration of neuroblasts. Together, our results highlight a close mutual relationship between spatiotemporal regulation of the primary cilium and efficient chain migration of neuroblasts in the postnatal brain

Limits on the Spin-Orbit Angle and Atmospheric Escape for the 22 Myr-old Planet AU Mic b

We obtained spectra of the pre-main sequence star AU Microscopii during a transit of its Neptune-sized planet to investigate its orbit and atmosphere. We used the high-dispersion near-infrared spectrograph IRD on the Subaru telescope to detect the Doppler "shadow" from the planet and constrain the projected stellar obliquity. Modeling of the observed planetary Doppler shadow suggests a spin-orbit alignment of the system ($\lambda=-4.7_{-6.4}^{+6.8}$ degrees), but additional observations are needed to confirm this finding. We use both the IRD data and spectra obtained with NIRSPEC on Keck-II to search for absorption in the 1083 nm line of metastable triplet He I by the planet's atmosphere and place an upper limit for the equivalent width of 3.7 m\AA at 99 $\%$ confidence. With this limit and a Parker wind model we constrain the escape rate from the atmosphere to $<0.15-0.45\, M_{\oplus}$ Gyr$^{-1}$, comparable to the rates predicted by an XUV energy-limited escape calculation and hydrodynamic models, but refinement of the planet mass is needed for rigorous tests.Comment: 10 pages, 5 figures, accepted for publication in ApJ Letter

Direct Imaging Explorations for Companions around Mid-Late M Stars from the Subaru/IRD Strategic Program

The Subaru telescope is currently performing a strategic program (SSP) using the high-precision near-infrared (NIR) spectrometer IRD to search for exoplanets around nearby mid/late-M~dwarfs via radial velocity (RV) monitoring. As part of the observing strategy for the exoplanet survey, signatures of massive companions such as RV trends are used to reduce the priority of those stars. However, this RV information remains useful for studying the stellar multiplicity of nearby M~dwarfs. To search for companions around such ``deprioritized" M~dwarfs, we observed 14 IRD-SSP targets using Keck/NIRC2 observations with pyramid wavefront sensing at NIR wavelengths, leading to high sensitivity to substellar-mass companions within a few arcseconds. We detected two new companions (LSPM~J1002+1459~B and LSPM~J2204+1505~B) and two new candidates that are likely companions (LSPM~J0825+6902~B and LSPM~J1645+0444~B) as well as one known companion. Including two known companions resolved by the IRD fiber injection module camera, we detected seven (four new) companions at projected separations between $\sim2-20$~au in total. A comparison of the colors with the spectral library suggests that LSPM~J2204+1505~B and LSPM~J0825+6902~B are located at the boundary between late-M and early-L spectral types. Our deep high-contrast imaging for targets where no bright companions were resolved did not reveal any additional companion candidates. The NIRC2 detection limits could constrain potential substellar-mass companions ($\sim10-75\ M_{\rm Jup}$) at 10~au or further. The failure with Keck/NIRC2 around the IRD-SSP stars having significant RV trends makes these objects promising targets for further RV monitoring or deeper imaging with JWST to search for smaller-mass companions below the NIRC2 detection limits.Comment: 16 pages, 8 figures, accepted for publication in A

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk