Loss of the Transcriptional Repressor PAG-3/Gfi-1 Results in Enhanced Neurosecretion that is Dependent on the Dense-Core Vesicle Membrane Protein IDA-1/IA-2

It is generally accepted that neuroendocrine cells regulate dense core vesicle (DCV) biogenesis and cargo packaging in response to secretory demands, although the molecular mechanisms of this process are poorly understood. One factor that has previously been implicated in DCV regulation is IA-2, a catalytically inactive protein phosphatase present in DCV membranes. Our ability to directly visualize a functional, GFP-tagged version of an IA-2 homolog in live Caenorhabditis elegans animals has allowed us to capitalize on the genetics of the system to screen for mutations that disrupt DCV regulation. We found that loss of activity in the transcription factor PAG-3/Gfi-1, which functions as a repressor in many systems, results in a dramatic up-regulation of IDA-1/IA-2 and other DCV proteins. The up-regulation of DCV components was accompanied by an increase in presynaptic DCV numbers and resulted in phenotypes consistent with increased neuroendocrine secretion. Double mutant combinations revealed that these PAG-3 mutant phenotypes were dependent on wild type IDA-1 function. Our results support a model in which IDA-1/IA-2 is a critical element in DCV regulation and reveal a novel genetic link to PAG-3-mediated transcriptional regulation. To our knowledge, this is the first mutation identified that results in increased neurosecretion, a phenotype that has clinical implications for DCV-mediated secretory disorders

Apparent source levels and active communication space of whistles of free-ranging Indo-Pacific humpback dolphins (Sousa chinensis) in the Pearl River Estuary and Beibu Gulf, China

Grants for this study was provided by the National Natural Science Foundation (NNSF) of China (Grant No.31070347), the Ministry of Science and Technology of China (Grant No. 2011BAG07B05-3), the Knowledge Innovation Program of the Chinese Academy of Sciences (Grant No. KSCX2-EW-Z-4) and the Special Fund for Agro-scientific Research in the Public Interest of the Ministry of Agriculture of China (Grant No. 201203086) to DW, the State Oceanic Administration of China (Grant No. 201105011-3) and NNSF of China (Grant No. 31170501) to KXW and the China Scholarship Council (Grant No. (2014)3026) to ZTW.Background . Knowledge of species-specific vocalization characteristics and their associated active communication space, the effective range over which a communication signal can be detected by a conspecific, is critical for understanding the impacts of underwater acoustic pollution, as well as other threats. Methods. We used a two-dimensional cross-shaped hydrophone array system to record the whistles of free-ranging Indo-Pacific humpback dolphins (Sousa chinensis) in shallow-water environments of the Pearl River Estuary (PRE) and Beibu Gulf (BG), China. Using hyperbolic position fixing, which exploits time differences of arrival of a signal between pairs of hydrophone receivers, we obtained source location estimates for whistles with good signal-to-noise ratio (SNR  ≥ 10 dB) and not polluted by other sounds and back-calculated their apparent source levels (ASL). Combining with the masking levels (including simultaneous noise levels, masking tonal threshold, and the Sousa auditory threshold) and the custom made site-specific sound propagation models, we further estimated their active communication space (ACS). Results. Humpback dolphins produced whistles with average root-mean-square ASL of 138.5 ± 6.8 (mean ± standard deviation) and 137.2 ± 7.0 dB re 1 µPa in PRE (N = 33) and BG (N = 209), respectively. We found statistically significant differences in ASLs among different whistle contour types. The mean and maximum ACS of whistles were estimated to be 14.7 ± 2.6 (median ± quartile deviation) and 17.1 ± 3.5 m in PRE, and 34.2 ± 9.5 and 43.5 ±12.2 m in BG. Using just the auditory threshold as the masking level produced the mean and maximum ACSat of 24.3 ± 4.8 and 35.7 ± 4.6 m for PRE, and 60.7 ± 18.1 and 74.3 ± 25.3 m for BG. The small ACSs were due to the high ambient noise level. Significant differences in ACSs were also observed among different whistle contour types. Discussion. Besides shedding some light for evaluating appropriate noise exposure levels and information for the regulation of underwater acoustic pollution, these baseline data can also be used for aiding the passive acoustic monitoring of dolphin populations, defining the boundaries of separate groups in a more biologically meaningful way during field surveys, and guiding the appropriate approach distance for local dolphin-watching boats and research boat during focal group following.Publisher PDFPeer reviewe

Geometric Nonlinear Meshless Analysis of Ribbed Rectangular Plates Based on the FSDT and the Moving Least-Squares Approximation

Based on the first-order shear deformation theory (FSDT) and the moving least-squares approximation, a new meshless model to study the geometric nonlinear problem of ribbed rectangular plates is presented. Considering the plate and the ribs separately, the displacement field, the stress, and strain of the plate and the ribs are obtained according to the moving least-squares approximation, the von Karman large deflection theory, and the FSDT. The ribs are attached to the plate by considering the displacement compatible condition along the connections between the ribs and the plate. The virtual strain energy formulation of the plate and the ribs is derived separately, and the nonlinear equilibrium equation of the entire ribbed plate is given by the virtual work principle. In the new meshless model for ribbed plates, there is no limitation to the rib position; for example, the ribs need not to be placed along the mesh lines of the plate as they need to be in FEM, and the change of rib positions will not lead to remeshing of the plate. The proposed model is compared with the FEM models from pieces of literature and ANSYS in several numerical examples, which proves the accuracy of the model

D 4 dopamine receptor high-resolution structures enable the discovery of selective agonists

Dopamine receptors are G protein-coupled receptors implicated in many neurological disorders. Different families of dopamine receptors are involved in different signaling pathways, so specificity is a key goal of therapeutics. Wang et al. present high-resolution crystal structures of the DRD4 dopamine receptor bound to the antipsychotic drug nemonapride. The high resolution of the structures facilitated ligand docking, and a DRD4-selective agonist was identified by computational screening of a large library, experimental testing of compounds with the best docking scores, and iterative cycles of docking and testing analogs of those compounds. The identified agonist had a high affinity for DRD4 and no measurable affinity for DRD2 or DRD3. Science , this issue p. [381][1] [1]: /lookup/doi/10.1126/science.aan546

Limited Antigenic Diversity in Contemporary H7 Avian-Origin Influenza A Viruses from North America

Subtype H7 avian–origin influenza A viruses (AIVs) have caused at least 500 confirmed human infections since 2003 and culling of \u3e75 million birds in recent years. Here we antigenically and genetically characterized 93 AIV isolates from North America (85 from migratory waterfowl [1976–2010], 7 from domestic poultry [1971–2012], and 1 from a seal [1980]). The hemagglutinin gene of these H7 viruses are separated from those from Eurasia. Gradual accumulation of nucleotide and amino acid substitutions was observed in the hemagglutinin of H7 AIVs from waterfowl and domestic poultry. Genotype characterization suggested that H7 AIVs in wild birds form diverse and transient internal gene constellations. Serologic analyses showed that the 93 isolates cross-reacted with each other to different extents. Antigenic cartography showed that the average antigenic distance among them was 1.14 units (standard deviation [SD], 0.57 unit) and that antigenic diversity among the H7 isolates we tested was limited. Our results suggest that the continuous genetic evolution has not led to significant antigenic diversity for H7 AIVs from North America. These findings add to our understanding of the natural history of IAVs and will inform public health decision-making regarding the threat these viruses pose to humans and poultry

Climatic warming in China during 1901-2015 based on an extended dataset of instrumental temperature records

Monthly mean instrumental surface air temperature (SAT) observations back to the nineteenth century in China are synthesized from different sources via specific quality-control, interpolation, and homogenization. Compared with the first homogenized long-term SAT dataset for China by Cao et al. (2013), which contained 18 stations mainly located in the middle and eastern part of China, the present dataset includes homogenized monthly SAT series at 32 stations, with an extended coverage especially towards western China. Missing values are interpolated by using observations at nearby stations including those from neighboring countries. Cross validation shows that the mean bias error (MBE) is generally small and falls between 0.45°C and -0.35°C. Multiple homogenization methods and available metadata are applied to assess the consistency of the time series and to adjust inhomogeneity biases. The homogenized annual mean SAT series show a range of trends between 1.1 and 4.0°C/century in northeastern China, between 0.4 and 1.9°C/century in southeastern China, and between 1.4 and 3.7°C/century in western China to the west of 105E (from the beginning years of the stations to 2015). The unadjusted data include unusually warm records during the 1940s and hence tend to underestimate the warming trends at a number of stations. The mean SAT series for China based on the Climate Anomaly Method shows a warming trend of 1.56°C/century during 1901-2015, larger than those based on other currently available datasets

Retinal tissue engineering using mouse retinal progenitor cells and a novel biodegradable, thin-film poly(e-caprolactone) nanowire scaffold

Retinal progenitor cells (RPCs) can be combined with nanostructured polymer scaffolds to generate composite grafts in culture. One strategy for repair of diseased retinal tissue involves implantation of composite grafts of this type in the subretinal space. In the present study, mouse retinal progenitor cells (RPCs) were cultured on laminin-coated novel nanowire poly(e-caprolactone)(PCL) scaffolds, and the survival, differentiation, and migration of these cells into the retina of C57bl/6 and rhodospsin −/− mouse retinal explants and transplant recipients were analyzed. RPCs were cultured on smooth PCL and both short (2.5 μm) and long (27 μm) nanowire PCL scaffolds. Scaffolds with adherent mRPCs were then either co-cultured with, or transplanted to, wild-type and rhodopsin −/− mouse retina. Robust RPC proliferation on each type of PCL scaffold was observed. Immunohistochemistry revealed that RPCs cultured on nanowire scaffolds increased expression of mature bipolar and photoreceptor markers. Reverse transcription polymerase chain reaction revealed down-regulation of several early progenitor markers. PCL-delivered RPCs migrated into the retina of both wild-type and rhodopsin knockout mice. The results provide evidence that RPCs proliferate and express mature retinal proteins in response to interactions with nanowire scaffolds. These composite grafts allow for the migration and differentiation of new cells into normal and degenerated retina

Postpartum depression in mothers and fathers: a structural equation model

open access articleBackground Post-partum depression (PPD) is a growing mental health concern worldwide. There is little evidence in the Chinese context of the relationship between paternal PPD and maternal PPD. Given the growing global concerns this relationship requires further exploration. Methods A survey was conducted with 950 total couples from March 2017 to December 2018. The study was conducted using a standardized questionnaire that included basic demographic information, information on the relationship between the mother-in-law and daughter-in-law, marital satisfaction (both maternal and paternal), and PPD symptoms. Structural Equation Modelling (SEM) analysis was used to explore the underlying mechanism for PPD symptoms in mothers and fathers. Results In 4.4% of the couples both the wife and the husband showed depressive symptoms. Maternal marital satisfaction showed a significant mediating effect on paternal PPD (B = -0.114, p < 0.01), and there was a direct effect of maternal PPD on paternal PPD (B = 0.31, p < 0.001). Conclusions This is the first study to investigate the possible correlation between maternal PPD, mother-in-law and daughter-in-law relationship satisfaction, maternal marital satisfaction, paternal marital satisfaction, and paternal PPD. It is important for future PPD interventions to target both maternal and paternal mental health, as well as the mechanisms identified that can lead to PPD

Tissue tropisms opt for transmissible reassortants during avian and swine influenza A virus co-infection in swine

Genetic reassortment between influenza A viruses (IAVs) facilitate emergence of pandemic strains, and swine are proposed as a “mixing vessel” for generating reassortants of avian and mammalian IAVs that could be of risk to mammals, including humans. However, how a transmissible reassortant emerges in swine are not well understood. Genomic analyses of 571 isolates recovered from nasal wash samples and respiratory tract tissues of a group of co-housed pigs (influenza-seronegative, avian H1N1 IAV–infected, and swine H3N2 IAV– infected pigs) identified 30 distinct genotypes of reassortants. Viruses recovered from lower respiratory tract tissues had the largest genomic diversity, and those recovered from turbinates and nasal wash fluids had the least. Reassortants from lower respiratory tracts had the largest variations in growth kinetics in respiratory tract epithelial cells, and the cold temperature in swine nasal cells seemed to select the type of reassortant viruses shed by the pigs. One reassortant in nasal wash samples was consistently identified in upper, middle, and lower respiratory tract tissues, and it was confirmed to be transmitted efficiently between pigs. Study findings suggest that, during mixed infections of avian and swine IAVs, genetic reassortments are likely to occur in the lower respiratory track, and tissue tropism is an important factor selecting for a transmissible reassortant