A putative ATPase mediates RNA transcription and capping in a dsRNA virus.

mRNA transcription in dsRNA viruses is a highly regulated process but the mechanism of this regulation is not known. Here, by nucleoside triphosphatase (NTPase) assay and comparisons of six high-resolution (2.9-3.1 Å) cryo-electron microscopy structures of cytoplasmic polyhedrosis virus with bound ligands, we show that the large sub-domain of the guanylyltransferase (GTase) domain of the turret protein (TP) also has an ATP-binding site and is likely an ATPase. S-adenosyl-L-methionine (SAM) acts as a signal and binds the methylase-2 domain of TP to induce conformational change of the viral capsid, which in turn activates the putative ATPase. ATP binding/hydrolysis leads to an enlarged capsid for efficient mRNA synthesis, an open GTase domain for His217-mediated guanylyl transfer, and an open methylase-1 domain for SAM binding and methyl transfer. Taken together, our data support a role of the putative ATPase in mediating the activation of mRNA transcription and capping within the confines of the virus

In situ structures of the segmented genome and RNA polymerase complex inside a dsRNA virus.

Viruses in the Reoviridae, like the triple-shelled human rotavirus and the single-shelled insect cytoplasmic polyhedrosis virus (CPV), all package a genome of segmented double-stranded RNAs (dsRNAs) inside the viral capsid and carry out endogenous messenger RNA synthesis through a transcriptional enzyme complex (TEC). By direct electron-counting cryoelectron microscopy and asymmetric reconstruction, we have determined the organization of the dsRNA genome inside quiescent CPV (q-CPV) and the in situ atomic structures of TEC within CPV in both quiescent and transcribing (t-CPV) states. We show that the ten segmented dsRNAs in CPV are organized with ten TECs in a specific, non-symmetric manner, with each dsRNA segment attached directly to a TEC. The TEC consists of two extensively interacting subunits: an RNA-dependent RNA polymerase (RdRP) and an NTPase VP4. We find that the bracelet domain of RdRP undergoes marked conformational change when q-CPV is converted to t-CPV, leading to formation of the RNA template entry channel and access to the polymerase active site. An amino-terminal helix from each of two subunits of the capsid shell protein (CSP) interacts with VP4 and RdRP. These findings establish the link between sensing of environmental cues by the external proteins and activation of endogenous RNA transcription by the TEC inside the virus

Prompt Tuning based Adapter for Vision-Language Model Adaption

Large pre-trained vision-language (VL) models have shown significant promise in adapting to various downstream tasks. However, fine-tuning the entire network is challenging due to the massive number of model parameters. To address this issue, efficient adaptation methods such as prompt tuning have been proposed. We explore the idea of prompt tuning with multi-task pre-trained initialization and find it can significantly improve model performance. Based on our findings, we introduce a new model, termed Prompt-Adapter, that combines pre-trained prompt tunning with an efficient adaptation network. Our approach beat the state-of-the-art methods in few-shot image classification on the public 11 datasets, especially in settings with limited data instances such as 1 shot, 2 shots, 4 shots, and 8 shots images. Our proposed method demonstrates the promise of combining prompt tuning and parameter-efficient networks for efficient vision-language model adaptation. The code is publicly available at: https://github.com/Jingchensun/prompt_adapter

Alchemical and structural distribution based representation for improved QML

We introduce a representation of any atom in any chemical environment for the generation of efficient quantum machine learning (QML) models of common electronic ground-state properties. The representation is based on scaled distribution functions explicitly accounting for elemental and structural degrees of freedom. Resulting QML models afford very favorable learning curves for properties of out-of-sample systems including organic molecules, non-covalently bonded protein side-chains, (H$_2$O)$_{40}$-clusters, as well as diverse crystals. The elemental components help to lower the learning curves, and, through interpolation across the periodic table, even enable "alchemical extrapolation" to covalent bonding between elements not part of training, as evinced for single, double, and triple bonds among main-group elements

Insights into midgut cell types and their crucial role in antiviral immunity in the lepidopteran model Bombyx mori

The midgut, a vital component of the digestive system in arthropods, serves as an interface between ingested food and the insect’s physiology, playing a pivotal role in nutrient absorption and immune defense mechanisms. Distinct cell types, including columnar, enteroendocrine, goblet and regenerative cells, comprise the midgut in insects and contribute to its robust immune response. Enterocytes/columnar cells, the primary absorptive cells, facilitate the immune response through enzyme secretions, while regenerative cells play a crucial role in maintaining midgut integrity by continuously replenishing damaged cells and maintaining the continuity of the immune defense. The peritrophic membrane is vital to the insect’s innate immunity, shielding the midgut from pathogens and abrasive food particles. Midgut juice, a mixture of digestive enzymes and antimicrobial factors, further contributes to the insect’s immune defense, helping the insect to combat invading pathogens and regulate the midgut microbial community. The cutting-edge single-cell transcriptomics also unveiled previously unrecognized subpopulations within the insect midgut cells and elucidated the striking similarities between the gastrointestinal tracts of insects and higher mammals. Understanding the intricate interplay between midgut cell types provides valuable insights into insect immunity. This review provides a solid foundation for unraveling the complex roles of the midgut, not only in digestion but also in immunity. Moreover, this review will discuss the novel immune strategies led by the midgut employed by insects to combat invading pathogens, ultimately contributing to the broader understanding of insect physiology and defense mechanisms

Genome-Wide Characterization of Endogenous Retroviruses in Bombyx mori Reveals the Relatives and Activity of env Genes

Endogenous retroviruses (ERVs) are retroviral sequences that remain fixed in the host genome, where they could play an important role. Some ERVs have been identified in insects and proven to have infectious properties. However, no information is available regarding Bombyx mori ERVs (BmERVs) to date. Here, we systematically identified 256 potential BmERVs in the silkworm genome via a whole-genome approach. BmERVs were relatively evenly distributed across each of the chromosomes and accounted for about 25% of the silkworm genome. All BmERVs were classified as young ERVs, with insertion times estimated to be less than 10 million years. Seven BmERVs possessing the env genes were identified. With the exception of the Orf133 Helicoverpa armigera nuclear polyhedrosis virus, the env sequences of BmERVs were distantly related to genes encoding F (Fa and Fb) and GP64 proteins from Group I and Group II NPVs. In addition, only the amino acid sequence of the BmERV-21 envelope protein shared a similar putative furin-like cleavage site and fusion peptide with Group II baculoviruses. All of the env genes in the seven BmERVs were verified to exist in the genome and be expressed in the midgut and fat bodies, which suggest that BmERVs might play an important role in the host biology

Construction of a Baculovirus-Silkworm Multigene Expression System and Its Application on Producing Virus-Like Particles

A new baculovirus-silkworm multigene expression system named Bombyx mori MultiBac is developed and described here, by which multiple expression cassettes can be introduced into the Bombyx mori nuclear polyhedrosis virus (BmNPV) genome efficiently. The system consists of three donor vectors (pCTdual, pRADM and pUCDMIG) and an invasive diaminopimelate (DAP) auxotrophic recipient E. coli containing BmNPV-Bacmid (BmBacmid) with a homologous recombination region, an attTn7 site and a loxp site. Two genes carried by pCTdual are firstly inserted into BmBacmid by homologous recombination, while the other eight genes in pRADM and pUCDMIG are introduced into BmBacmid through Tn7 transposition and cre-loxp recombination. Then the invasive and DAP auxotrophic E. coli carrying recombinant BmBacmid is directly injected into silkworm for expressing heterologous genes in larvae or pupae. Three structural genes of rotavirus and three fluorescent genes have been simultaneously expressed in silkworm larvae using our new system, resulting in the formation of virus-like particles (VLPs) of rotavirus and the color change of larvae. The VLPs were purified from hemolymph by ultracentrifugation using CsCl gradients, with a yield of 12.7 µg per larva. For the great capacity of foreign genes and the low cost of feeding silkworm, this high efficient BmMultiBac expression system provides a suitable platform to produce VLPs or protein complexes

An empirical investigation of taxi driver response behavior to ride-hailing requests: A spatio-temporal perspective.

Using data provided by a ride-hailing platform, this paper examines the factors that affect taxi driver response behavior to ride-hailing requests. The empirical investigation from a driver's perspective is of great importance for ride-hailing service providers, given that approximately 40% of the hailing requests receive no response from any driver. To comprehensively understand taxi driver response behavior, we use a rich dataset to generate variables related to the spatio-temporal supply-demand intensities, the economic incentives, the requests' and the drivers' characteristics. The results show that drivers are more likely to respond to requests with economic incentives (especially a firm subsidy), and those with a lower spatio-temporal demand intensity or a higher spatio-temporal supply intensity. In addition, drivers are more likely to respond to requests involving rides covering a greater geographical distance and to those with a smaller number of repeated submissions. The drivers' characteristics, namely, the number of requests received and the number of requests responded, however, have relatively little impacts on their response probability to the current request. Our findings contribute to the related literature and provide managerial implications for ride-hailing service providers

A putative ATPase mediates RNA transcription and capping in a dsRNA virus.

mRNA transcription in dsRNA viruses is a highly regulated process but the mechanism of this regulation is not known. Here, by nucleoside triphosphatase (NTPase) assay and comparisons of six high-resolution (2.9-3.1 Å) cryo-electron microscopy structures of cytoplasmic polyhedrosis virus with bound ligands, we show that the large sub-domain of the guanylyltransferase (GTase) domain of the turret protein (TP) also has an ATP-binding site and is likely an ATPase. S-adenosyl-L-methionine (SAM) acts as a signal and binds the methylase-2 domain of TP to induce conformational change of the viral capsid, which in turn activates the putative ATPase. ATP binding/hydrolysis leads to an enlarged capsid for efficient mRNA synthesis, an open GTase domain for His217-mediated guanylyl transfer, and an open methylase-1 domain for SAM binding and methyl transfer. Taken together, our data support a role of the putative ATPase in mediating the activation of mRNA transcription and capping within the confines of the virus