SPGP: Structure Prototype Guided Graph Pooling

While graph neural networks (GNNs) have been successful for node classification tasks and link prediction tasks in graph, learning graph-level representations still remains a challenge. For the graph-level representation, it is important to learn both representation of neighboring nodes, i.e., aggregation, and graph structural information. A number of graph pooling methods have been developed for this goal. However, most of the existing pooling methods utilize k-hop neighborhood without considering explicit structural information in a graph. In this paper, we propose Structure Prototype Guided Pooling (SPGP) that utilizes prior graph structures to overcome the limitation. SPGP formulates graph structures as learnable prototype vectors and computes the affinity between nodes and prototype vectors. This leads to a novel node scoring scheme that prioritizes informative nodes while encapsulating the useful structures of the graph. Our experimental results show that SPGP outperforms state-of-the-art graph pooling methods on graph classification benchmark datasets in both accuracy and scalability.Comment: 18 pages, 6 figure

M gene reassortment in H9N2 influenza virus promotes early infection and replication: contribution to rising virus prevalence in chickens in China

Segment reassortment and base mutagenesis of influenza A viruses are the primary routes to the rapid evolution of high fitness virus genotypes. We recently described a predominant G57 genotype of avian H9N2 viruses that caused country-wide outbreaks in chickens in China during 2010-2013 which led to the zoonotic emergence of H7N9 viruses. One of the key features of the G57 genotype is the substitution of the earlier BJ/94-like M gene with the G1-like M gene of quail origin. We report here on the functional significance of the G1-like M gene in H9N2 viruses in conferring increased infection severity and infectivity in primary chicken embryonic fibroblasts and chickens. H9N2 virus housing the G1-like M gene, in place of BJ/94-like M gene, showed early surge in viral mRNA and vRNA transcription that were associated with enhanced viral protein production, and with early elevated release of progeny virus comprising largely spherical rather than filamentous virions. Importantly, H9N2 virus with G1-like M gene conferred extrapulmonary virus spread in chickens. Five highly represented signature amino acid residues (37A, 95K, 224N and 242N in M1 protein, and 21G in M2 protein) encoded by the prevalent G1-like M gene were demonstrated as prime contributors to enhanced infectivity. Therefore, the genetic evolution of M gene in H9N2 virus increases reproductive virus fitness, indicating its contribution to rising virus prevalence in chickens in China. Importance We recently described the circulation of a dominant genotype (G57) of H9N2 viruses in country-wide outbreaks in chickens in China, which was responsible through reassortment for the emergence of H7N9 viruses that cause severe human infections. A key feature of the G57 genotype H9N2 virus is the presence of quail origin G1-like M gene which had replaced the earlier BJ/94-like M gene. We found that H9N2 virus with G1-like M gene, but not BJ/94-like M gene, showed early surge in progeny virus production, more severe pathology and extrapulmonary virus spread in chickens. Five highly represented amino acid residues in M1 and M2 proteins derived from G1-like M gene were shown to mediate enhanced virus infectivity. These observations enhance what we currently know about the roles of reassortment and mutations on virus fitness and have implications for assessing the potential of variant influenza viruses that can cause rising prevalence in chickens

Highly pathogenic avian influenza H5N6 viruses exhibit enhanced affinity for human type sialic acid receptor and in-contact transmission in model ferrets

Since May 2014, highly pathogenic avian influenza H5N6 virus has been reported to cause six severe human infections three of which were fatal. The biological properties of this subtype, in particular its relative pathogenicity and transmissibility in mammals, are not known. We characterized the virus receptor-binding affinity, pathogenicity, and transmissibility in mice and ferrets of four H5N6 isolates derived from waterfowl in China from 2013-2014. All four H5N6 viruses have acquired a binding affinity for human-like SA alpha 2,6Gal-linked receptor to be able to attach to human tracheal epithelial and alveolar cells. The emergent H5N6 viruses, which share high sequence similarity with the human isolate A/Guangzhou/39715/2014 (H5N6), were fully infective and highly transmissible by direct contact in ferrets but showed less-severe pathogenicity than the parental H5N1 virus. The present results highlight the threat of emergent H5N6 viruses to poultry and human health and the need to closely track their continual adaptation in humans

Flexible Platform of Acoustofluidics and Metamaterials with Decoupled Resonant Frequencies

The key challenge for a lab-on-chip (LOC) device is the seamless integration of key elements of biosensing and actuation (e.g., biosampling or microfluidics), which are conventionally realised using different technologies. In this paper, we report a convenient and efficient LOC platform fabricated using an electrode patterned flexible printed circuit board (FPCB) pressed onto a piezoelectric film coated substrate, which can implement multiple functions of both acoustofluidics using surface acoustic waves (SAWs) and sensing functions using electromagnetic metamaterials, based on the same electrode on the FPCB. We explored the actuation capability of the integrated structure by pumping a sessile droplet using SAWs in the radio frequency range. We then investigated the hybrid sensing capability (including both physical and chemical ones) of the structure employing the concept of electromagnetic split-ring resonators (SRRs) in the microwave frequency range. The originality of this sensing work is based on the premise that the proposed structure contains three completely decoupled resonant frequencies for sensing applications and each resonance has been used as a separate physical or a chemical sensor. This feature compliments the acoustofluidic capability and is well-aligned with the goals set for a successful LOC device

Striatal Transcriptome and Interactome Analysis of Shank3-overexpressing Mice Reveals the Connectivity between Shank3 and mTORC1 Signaling

Mania causes symptoms of hyperactivity, impulsivity, elevated mood, reduced anxiety and decreased need for sleep, which suggests that the dysfunction of the striatum, a critical component of the brain motor and reward system, can be causally associated with mania. However, detailed molecular pathophysiology underlying the striatal dysfunction in mania remains largely unknown. In this study, we aimed to identify the molecular pathways showing alterations in the striatum of SH3 and multiple ankyrin repeat domains 3 (Shank3)-overexpressing transgenic (TG) mice that display manic-like behaviors. The results of transcriptome analysis suggested that mammalian target of rapamycin complex 1 (mTORC1) signaling may be the primary molecular signature altered in the Shank3 TG striatum. Indeed, we found that striatal mTORC1 activity, as measured by mTOR S2448 phosphorylation, was significantly decreased in the Shank3 TG mice compared to wild-type (WT) mice. To elucidate the potential underlying mechanism, we re-analyzed previously reported protein interactomes, and detected a high connectivity between Shank3 and several upstream regulators of mTORC1, such as tuberous sclerosis 1 (TSC1), TSC2 and Ras homolog enriched in striatum (Rhes), via 94 common interactors that we denominated “Shank3-mTORC1 interactome”. We noticed that, among the 94 common interactors, 11 proteins were related to actin filaments, the level of which was increased in the dorsal striatum of Shank3 TG mice. Furthermore, we could co-immunoprecipitate Shank3, Rhes and Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1) proteins from the striatal lysate of Shank3 TG mice. By comparing with the gene sets of psychiatric disorders, we also observed that the 94 proteins of Shank3-mTORC1 interactome were significantly associated with bipolar disorder (BD). Altogether, our results suggest a protein interaction-mediated connectivity between Shank3 and certain upstream regulators of mTORC1 that might contribute to the abnormal striatal mTORC1 activity and to the manic-like behaviors of Shank3 TG mice

Molecular mechanisms for the adaptive switching between the OAS/RNase L and OASL/RIG-I pathways in birds and mammals:Adaptive exchanging of the OAS/RNase L and OASL/RIG-I pathway

Host cells develop the OAS/RNase L [2′–5′–oligoadenylate synthetase (OAS)/ribonuclease L] system to degrade cellular and viral RNA, and/or the OASL/RIG-I (2′–5′–OAS like/retinoic acid inducible protein I) system to enhance RIG-I-mediated IFN induction, thus providing the first line of defense against viral infection. The 2′–5′–OAS-like (OASL) protein may activate the OAS/RNase L system using its typical OAS-like domain (OLD) or mimic the K63-linked pUb to enhance antiviral activity of the OASL/RIG-I system using its two tandem ubiquitin-like domains (UBLs). We first describe that divergent avian (duck and ostrich) OASL inhibit the replication of a broad range of RNA viruses by activating and magnifying the OAS/RNase L pathway in a UBL-dependent manner. This is in sharp contrast to mammalian enzymatic OASL, which activates and magnifies the OAS/RNase L pathway in a UBL-independent manner, similar to 2′–5′–oligoadenylate synthetase 1 (OAS1). We further show that both avian and mammalian OASL can reversibly exchange to activate and magnify the OAS/RNase L and OASL/RIG-I system by introducing only three key residues, suggesting that ancient OASL possess 2–5A [px5′A(2′p5′A)n; x = 1-3; n ≥ 2] activity and has functionally switched to the OASL/RIG-I pathway recently. Our findings indicate the molecular mechanisms involved in the switching of avian and mammalian OASL molecules to activate and enhance the OAS/RNase L and OASL/RIG-I pathways in response to infection by RNA viruses

A new chromosome-scale duck genome shows a major histocompatibility complex with several expanded multigene families

BACKGROUND: The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A virus (IAV), harbors almost all subtypes of IAVs and resists to many IAVs which cause extreme virulence in chicken and human. However, the response of duck's adaptive immune system to IAV infection is poorly characterized due to lack of a detailed gene map of the major histocompatibility complex (MHC).RESULTS: We herein reported a chromosome-scale Beijing duck assembly by integrating Nanopore, Bionano, and Hi-C data. This new reference genome SKLA1.0 covers 40 chromosomes, improves the contig N50 of the previous duck assembly with highest contiguity (ZJU1.0) of more than a 5.79-fold, surpasses the chicken and zebra finch references in sequence contiguity and contains a complete genomic map of the MHC. Our 3D MHC genomic map demonstrated that gene family arrangement in this region was primordial; however, families such as AnplMHCI, AnplMHCIIβ, AnplDMB, NKRL (NK cell receptor-like genes) and BTN underwent gene expansion events making this area complex. These gene families are distributed in two TADs and genes sharing the same TAD may work in a co-regulated model.CONCLUSIONS: These observations supported the hypothesis that duck's adaptive immunity had been optimized with expanded and diversified key immune genes which might help duck to combat influenza virus. This work provided a high-quality Beijing duck genome for biological research and shed light on new strategies for AIV control.</p