Prokineticin 2 Is a Target Gene of Proneural Basic Helix-Loop-Helix Factors for Olfactory Bulb Neurogenesis

Prokineticin 2, a cysteine-rich secreted protein, regulates diverse biological functions including the neurogenesis of olfactory bulb. Here we show that the PK2 gene is a functional target gene of proneural basic helix-loop-helix (bHLH) factors. Neurogenin 1 and MASH1 activate PK2 transcription by binding to E-box motifs on the PK2 promoter with the same set of E-boxes critical for another pair of bHLH factors, CLOCK and BMAL1, in the regulation of circadian clock. Our results establish PK2 as a common functional target gene for different bHLH transcriptional factors in mediating their respective functions

One Solution to the Mass Budget Problem for Planet Formation: Optically Thick Disks with Dust Scattering

Atacama Large Millimeter Array (ALMA) surveys have suggested that the dust in Class II disks may not be enough to explain the averaged solid mass in exoplanets, under the assumption that the mm disk continuum emission is optically thin. This optically thin assumption seems to be supported by recent Disk Substructures at High Angular Resolution Project (DSHARP) observations where the measured optical depths are mostly less than one. However, we point out that dust scattering can considerably reduce the emission from an optically thick region. If that scattering is ignored, an optically thick disk with scattering can be misidentified as an optically thin disk. Dust scattering in more inclined disks can reduce the intensity even further, making the disk look even fainter. The measured optical depth of ~0.6 in several DSHARP disks can be naturally explained by optically thick dust with an albedo of ~0.9 at 1.25 mm. Using the DSHARP opacity, this albedo corresponds to a dust population with the maximum grain size (s max) of 0.1–1 mm. For optically thick scattering disks, the measured spectral index α can be either larger or smaller than 2 depending on whether the dust albedo increases or decreases with wavelength. We describe how this optically thick scattering scenario could explain the observed scaling between submm continuum sizes and luminosities, and might help ease the tension between the dust size constraints from polarization and dust continuum measurements. We suggest that a significant amount of disk mass can be hidden from ALMA observations and longer wavelength observations (e.g., Very Large Array or Square Kilometre Array) are desired to probe the dust mass in disks

Species specific exome probes reveal new insights in positively selected genes in nonhuman primates

Nonhuman primates (NHP) are important biomedical animal models for the study of human disease. Of these, the most widely used models in biomedical research currently are from the genus Macaca. However, evolutionary genetic divergence between human and NHP species makes human-based probes inefficient for the capture of genomic regions of NHP for sequencing and study. Here we introduce a new method to resequence the exome of NHP species by a designed capture approach specifically targeted to the NHP, and demonstrate its superior performance on four NHP species or subspecies. Detailed investigation on biomedically relevant genes demonstrated superior capture by the new approach. We identified 28 genes that appeared to be pseudogenized and inactivated in macaque. Finally, we identified 187 genes showing strong evidence for positive selection across all branches of the primate phylogeny including many novel findings

Mollusc aquaculture homogenizes intertidal soft-sediment communities along the 18,400 km long coastline of China

Abstract Aim Molluscs are important grazers, filter and deposit feeders, scavengers and predators, which in turn are food for shorebirds, fish and people. Some species, targeted as human food, have been cultured along the Chinese coast for hundreds of years. To examine whether aquacultural practices have meanwhile affected biodiversity gradients, we measured mollusc community structure along the coast of China in habitats which are intensively used by humans. Location Chinese coast. Methods We sampled 21 intertidal sites spanning 20 latitudinal degrees and 18,400 km of coastline. We assessed alpha diversity to verify whether mollusc communities exhibit the expected biodiversity gradient with latitude and beta diversity gradients with distance. To examine whether human activities such as transportation and culturing could have affected these patterns, we distinguished commercial from non-commercial mollusc species and compared the differences in distribution, density, alpha diversity and beta diversity. Results We found non-commercial species showed the expected biodiversity gradients. Commercial species (a) dominated the intertidal mollusc communities at 19 of the 21 sites and compared with non-commercial species, (b) exhibited wider geographical distributions, (c) showed no significant change in Bray-Curtis index (abundance-based beta diversity) with either geographical or climatic distance, (d) exhibited lower average dissimilarities and (e) did not show a decrease in species richness and Shannon diversity with latitude. Combining all species, trends were the same as for the commercial species. Main conclusions A few cultured species dominated the intertidal mollusc communities in high densities along the Chinese coastline, taking over the ecological roles of the native species but not driving them extinct. In this way, aquacultural practices have exerted a homogenizing influence strong enough to erase basic biodiversity gradients. Since molluscs are food for the growing human population and the shrinking populations of migratory animals, coastal planning and management of both intertidal habitats and the exploitative activities employed need to incorporate these dimensions

PROSAC: A Submillimeter Array Survey of Low-Mass Protostars. I. Overview of Program: Envelopes, Disks, Outflows and Hot Cores

This paper presents a large spectral line and continuum survey of 8 deeply embedded, low-mass protostellar cores using the Submillimeter Array. Each source was observed in high excitation lines of some of the most common molecular species, CO, HCO+, CS, SO, H2CO, CH3OH and SiO. Line emission from 11 species originating from warm and dense gas have been imaged at high angular resolution (1-3"; typically 200-600 AU) together with continuum emission at 230 GHz (1.3 mm) and 345 GHz (0.8 mm). Compact continuum emission is observed for all sources which likely originates in marginally optically thick circumstellar disks, with typical lower limits to their masses of 0.1 M_sun (1-10% of the masses of their envelopes) and having a dust opacity law with beta approximately 1. Prominent outflows are present in CO 2-1 observations in all sources: the most diffuse outflows are found in the sources with the lowest ratios of disk-to-envelope mass, and it is suggested that these sources are in a phase where accretion of matter from the envelope has almost finished and the remainder of the envelope material is being dispersed by the outflows. Other characteristic dynamical signatures are found with inverse P Cygni profiles indicative of infalling motions seen in the 13CO 2-1 lines toward NGC1333-IRAS4A and -IRAS4B. Outflow-induced shocks are present on all scales in the protostellar environments and are most clearly traced by the emission of CH3OH in NGC1333-IRAS4A and -IRAS4B. These observations suggest that the emission of CH3OH and H2CO from these proposed "hot corinos" are related to the shocks caused by the protostellar outflows. Only one source, NGC1333-IRAS2A, has evidence for hot, compact CH3OH emission coincident with the embedded protostar.Comment: Accepted for publication in ApJ (52 pages; 9 figures). Abstract abridge

Non-detection of He I in the atmosphere of GJ1214b with Keck/NIRSPEC, at a time of minimal telluric contamination

Observations of helium in exoplanet atmospheres may reveal the presence of large gaseous envelopes, and indicate ongoing atmospheric escape. Orell-Miquel et al. (2022) used CARMENES to measure a tentative detection of helium for the sub-Neptune GJ 1214b, with a peak excess absorption reaching over 2% in transit depth at 10830 Angstroms. However, several non-detections of helium had previously been reported for GJ 1214b. One explanation for the discrepancy was contamination of the planetary signal by overlapping telluric absorption- and emission lines. We used Keck/NIRSPEC to observe another transit of GJ 1214b at 10830 Angstroms, at a time of minimal contamination by telluric lines, and did not observe planetary helium absorption. Accounting for correlated noise in our measurement, we place an upper limit on the excess absorption size of 1.22% (95% confidence). We find that the discrepancy between the CARMENES and NIRSPEC observations is unlikely to be caused by using different instruments or stellar activity. It is currently unclear whether the difference is due to correlated noise in the observations, or variability in the planetary atmosphere.Comment: Accepted for publication in ApJ

Genome-wide assessment of genetic risk for systemic lupus erythematosus and disease severity.

Using three European and two Chinese genome-wide association studies (GWAS), we investigated the performance of genetic risk scores (GRSs) for predicting the susceptibility and severity of systemic lupus erythematosus (SLE), using renal disease as a proxy for severity. We used four GWASs to test the performance of GRS both cross validating within the European population and between European and Chinese populations. The performance of GRS in SLE risk prediction was evaluated by receiver operating characteristic (ROC) curves. We then analyzed the polygenic nature of SLE statistically. We also partitioned patients according to their age-of-onset and evaluated the predictability of GRS in disease severity in each age group. We found consistently that the best GRS in the prediction of SLE used SNPs associated at the level of P < 1e-05 in all GWAS data sets and that SNPs with P-values above 0.2 were inflated for SLE true positive signals. The GRS results in an area under the ROC curve ranging between 0.64 and 0.72, within European and between the European and Chinese populations. We further showed a significant positive correlation between a GRS and renal disease in two independent European GWAS (Pcohort1 = 2.44e-08; Pcohort2 = 0.00205) and a significant negative correlation with age of SLE onset (Pcohort1 = 1.76e-12; Pcohort2 = 0.00384). We found that the GRS performed better in the prediction of renal disease in the 'later onset' compared with the 'earlier onset' group. The GRS predicts SLE in both European and Chinese populations and correlates with poorer prognostic factors: young age-of-onset and lupus nephritis.China Scholarship Council (CSC) & National Science Foundation of China grant 8180163

Differential Effects of an O-GlcNAcase Inhibitor on Tau Phosphorylation

Abnormal hyperphosphorylation of microtubule-associated protein tau plays a crucial role in neurodegeneration in Alzheimer's disease (AD). The aggregation of hyperphosphorylated tau into neurofibrillary tangles is also a hallmark brain lesion of AD. Tau phosphorylation is regulated by tau kinases, tau phosphatases, and O-GlcNAcylation, a posttranslational modification of proteins on the serine or threonine residues with β-N-acetylglucosamine (GlcNAc). O-GlcNAcylation is dynamically regulated by O-GlcNAc transferase, the enzyme catalyzing the transfer of GlcNAc to proteins, and N-acetylglucosaminidase (OGA), the enzyme catalyzing the removal of GlcNAc from proteins. Thiamet-G is a recently synthesized potent OGA inhibitor, and initial studies suggest it can influence O-GlcNAc levels in the brain, allowing OGA inhibition to be a potential route to altering disease progression in AD. In this study, we injected thiamet-G into the lateral ventricle of mice to increase O-GlcNAcylation of proteins and investigated the resulting effects on site-specific tau phosphorylation. We found that acute thiamet-G treatment led to a decrease in tau phosphorylation at Thr181, Thr212, Ser214, Ser262/Ser356, Ser404 and Ser409, and an increase in tau phosphorylation at Ser199, Ser202, Ser396 and Ser422 in the mouse brain. Investigation of the major tau kinases showed that acute delivery of a high dose of thiamet-G into the brain also led to a marked activation of glycogen synthase kinase-3β (GSK-3β), possibly as a consequence of down-regulation of its upstream regulating kinase, AKT. However, the elevation of tau phosphorylation at the sites above was not observed and GSK-3β was not activated in cultured adult hippocampal progenitor cells or in PC12 cells after thiamet-G treatment. These results suggest that acute high-dose thiamet-G injection can not only directly antagonize tau phosphorylation, but also stimulate GSK-3β activity, with the downstream consequence being site-specific, bi-directional regulation of tau phosphorylation in the mammalian brain

Observation of the nonlinear Hall effect under time reversal symmetric conditions

The electrical Hall effect is the production of a transverse voltage under an out-of-plane magnetic field. Historically, studies of the Hall effect have led to major breakthroughs including the discoveries of Berry curvature and the topological Chern invariants. In magnets, the internal magnetization allows Hall conductivity in the absence of external magnetic field. This anomalous Hall effect (AHE) has become an important tool to study quantum magnets. In nonmagnetic materials without external magnetic fields, the electrical Hall effect is rarely explored because of the constraint by time-reversal symmetry. However, strictly speaking, only the Hall effect in the linear response regime, i.e., the Hall voltage linearly proportional to the external electric field, identically vanishes due to time-reversal symmetry. The Hall effect in the nonlinear response regime, on the other hand, may not be subject to such symmetry constraints. Here, we report the observation of the nonlinear Hall effect (NLHE) in the electrical transport of the nonmagnetic 2D quantum material, bilayer WTe2. Specifically, flowing an electrical current in bilayer WTe2 leads to a nonlinear Hall voltage in the absence of magnetic field. The NLHE exhibits unusual properties sharply distinct from the AHE in metals: The NLHE shows a quadratic I-V characteristic; It strongly dominates the nonlinear longitudinal response, leading to a Hall angle of about 90 degree. We further show that the NLHE directly measures the "dipole moment" of the Berry curvature, which arises from layer-polarized Dirac fermions in bilayer WTe2. Our results demonstrate a new Hall effect and provide a powerful methodology to detect Berry curvature in a wide range of nonmagnetic quantum materials in an energy-resolved way