Channel-aware low Earth orbit satellite cluster networking for space-to-Earth laser communication: reliability and bandwidth advantages.

The reliability of the space-to-Earth laser communication plays a crucial role in providing uninterrupted real-time services in satellite optical networks. In traditional satellite optical networks, the space-to-Earth laser communication is carried out using a monolithic satellite in close proximity to the target optical ground station. However, the reliability of the communication in this approach is heavily influenced by the atmospheric environment. For instance, variations in cloud thickness can cause fluctuations in the link quality of the space-to-Earth laser communication, significantly reducing its reliability. This study proposes an innovative channel-adaptive space-to-Earth laser communication (CA-S2E-LC) architecture based on satellite cluster optical networking (SCON). SCON provides space-diversity link sets, reducing the probability of space-to-Earth laser communications affected by clouds. By leveraging the perception of link quality, the CA-S2E-LC architecture can adaptively choose the better space-to-Earth laser communication links established by member satellites within a satellite cluster under different environments, and properly schedule the resource, ensuring reliable space-to-Earth laser communication. The principles of the SCON is analyzed and the implementation of the CA-S2E-LC architecture is demonstrated through the explanation of hardware and functional modules, workflows, finite state machines, and strategies. Simulation results demonstrate that the CA-S2E-LC architecture can significantly enhance communication reliability and capacity compared with the traditional monolithic satellite. Furthermore, the workflow of the architecture is demonstrated to validate the feasibility.

Real-time FPGA prototyping of Doppler frequency shift compensation using DSP-assisted automatic frequency control.

This Letter presents a real-time coherent receiver using digital signal processing (DSP)-assisted automatic frequency control (AFC) to compensate for the Doppler frequency shift (DFS). DFS compensation range of ±8 GHz and the frequency shifting rate of 33 MHz/s are demonstrated in an FPGA-based 2.5 Gbaud QPSK coherent optical system. The experimental results indicate that the scheme achieves a sensitivity of -47 dBm at a bit error rate (BER) of 2E-4. The power penalty induced by the DFS compensation is less than 1 dB.

Real-time low-complexity diversity combining algorithm for free space coherent optical communication systems over atmospheric turbulence channel.

A novel diversity combining scheme, in conjunction with the complex-valued decision-directed least mean square (CV-DD-LMS) algorithm, is evaluated, and a real-time experimental validation is presented. This proposed scheme employs the CV-DD-LMS algorithm to concurrently perform beam combination and carrier phase recovery (CPR), thereby effectively reducing the overall complexity of digital signal processing. Furthermore, in the numerical simulation, under a low signal-to-noise ratio (SNR), a scheme utilizing the CV-DD-LMS algorithm effectively avoids cycle slips (CS) and outperforms schemes employing independent CPR modules. We experimentally validate this novel scheme by implementing it on an FPGA in a real-time 2.5Gb/s QPSK diversity-receiving system with three inputs. The back-to-back sensitivity is assessed using static received optical power, while the dynamic performance is evaluated by employing variable optical attenuators (VOAs) to simulate a power fluctuation at a frequency of 100kHz. The result proves that the implementation of the CV-DD-LMS algorithm yields stable performance while effectively reducing computational complexity.

Nonlinear transmission performance comparison employing 60 × 416.7-Gb/s TPS-64QAM and UD-16QAM systems with limited bandwidth.

The impacts of limited bandwidth on the nonlinear transmission performance are investigated by employing a truncated probabilistic shaped 64-ary quadrature amplitude modulation (TPS-64QAM) and a uniformly distributed 16-ary quadrature amplitude modulation (UD-16QAM) over a bandwidth-limited 75-GHz spaced 25-Tb/s (60 × 416.7 Gb/s) 6300-km transmission system. In terms of nonlinear performance measured by optimal launch power, theoretical analyses show that a 0.4-dB improvement could be introduced by UD-16QAM with respect to TPS-64QAM over a 6300-km transmission without limited bandwidth. However, contrary results would be observed that TPS-64QAM would outperform UD-16QAM by about 0.8 dB in terms of optimal launch power when the impacts of limited bandwidth are considered. Besides, numerical simulations and experimental results could both validate that about 1.0-dB optimal launch power improvement could be obtained by TPS-64QAM under bandwidth-limited cases, which is roughly similar to the results of theoretical analyses. Additionally, WDM experimental results show that all 60 tested channels could agree with the BER requirements by employing TPS-64QAM, further validating the superiority of TPS-64QAM compared to UD-16QAM under bandwidth-limited cases.

Chemogenetics as a neuromodulatory approach to treating neuropsychiatric diseases and disorders.

Chemogenetics enables precise, non-invasive, and reversible modulation of neural activity via the activation of engineered receptors that are pharmacologically selective to endogenous or exogenous ligands. With recent advances in therapeutic gene delivery, chemogenetics is poised to support novel interventions against neuropsychiatric diseases and disorders. To evaluate its translational potential, we performed a scoping review of applications of chemogenetics that led to the reversal of molecular and behavioral deficits in studies relevant to neuropsychiatric diseases and disorders. In this review, we present these findings and discuss the potential and challenges for using chemogenetics as a precision medicine-based neuromodulation strategy.

Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection.

Pigs are considered as important hosts or "mixing vessels" for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses. Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses.

Integrative Analysis of Machine Learning and Molecule Docking Simulations for Ischemic Stroke Diagnosis and Therapy.

Due to the narrow therapeutic window and high mortality of ischemic stroke, it is of great significance to investigate its diagnosis and therapy. We employed weighted gene coexpression network analysis (WGCNA) to ascertain gene modules related to stroke and used the maSigPro R package to seek the time-dependent genes in the progression of stroke. Three machine learning algorithms were further employed to identify the feature genes of stroke. A nomogram model was built and applied to evaluate the stroke patients. We analyzed single-cell RNA sequencing (scRNA-seq) data to discern microglia subclusters in ischemic stroke. The RNA velocity, pseudo time, and gene set enrichment analysis (GSEA) were performed to investigate the relationship of microglia subclusters. Connectivity map (CMap) analysis and molecule docking were used to screen a therapeutic agent for stroke. A nomogram model based on the feature genes showed a clinical net benefit and enabled an accurate evaluation of stroke patients. The RNA velocity and pseudo time analysis showed that microglia subcluster 0 would develop toward subcluster 2 within 24 h from stroke onset. The GSEA showed that the function of microglia subcluster 0 was opposite to that of subcluster 2. AZ_628, which screened from CMap analysis, was found to have lower binding energy with Mmp12, Lgals3, Fam20c, Capg, Pkm2, Sdc4, and Itga5 in microglia subcluster 2 and maybe a therapeutic agent for the poor development of microglia subcluster 2 after stroke. Our study presents a nomogram model for stroke diagnosis and provides a potential molecule agent for stroke therapy.

Reassortment with dominant chicken H9N2 influenza virus contributed to the fifth H7N9 virus human epidemic.

H9N2 Avian influenza virus (AIV) is regarded as a principal donor of viral genes through reassortment to co-circulating influenza viruses that can result in zoonotic reassortants. Whether H9N2 virus can maintain sustained evolutionary impact on such reassortants is unclear. Since 2013, avian H7N9 virus had caused five sequential human epidemics in China; the fifth wave in 2016-2017 was by far the largest but the mechanistic explanation behind the scale of infection is not clear. Here, we found that, just prior to the fifth H7N9 virus epidemic, H9N2 viruses had phylogenetically mutated into new sub-clades, changed antigenicity and increased its prevalence in chickens vaccinated with existing H9N2 vaccines. In turn, the new H9N2 virus sub-clades of PB2 and PA genes, housing mammalian adaptive mutations, were reassorted into co-circulating H7N9 virus to create a novel dominant H7N9 virus genotype that was responsible for the fifth H7N9 virus epidemic. H9N2-derived PB2 and PA genes in H7N9 virus conferred enhanced polymerase activity in human cells at 33°C and 37°C, and increased viral replication in the upper and lower respiratory tracts of infected mice which could account for the sharp increase in human cases of H7N9 virus infection in the 2016-2017 epidemic. The role of H9N2 virus in the continual mutation of H7N9 virus highlights the public health significance of H9N2 virus in the generation of variant reassortants of increasing zoonotic potential.IMPORTANCEAvian H9N2 influenza virus, although primarily restricted to chicken populations, is a major threat to human public health by acting as a donor of variant viral genes through reassortment to co-circulating influenza viruses. We established that the high prevalence of evolving H9N2 virus in vaccinated flocks played a key role, as donor of new sub-clade PB2 and PA genes in the generation of a dominant H7N9 virus genotype (G72) with enhanced infectivity in humans during the 2016-2017 N7N9 virus epidemic. Our findings emphasize that the ongoing evolution of prevalent H9N2 virus in chickens is an important source, via reassortment, of mammalian adaptive genes for other influenza virus subtypes. Thus, close monitoring of prevalence and variants of H9N2 virus in chicken flocks is necessary in the detection of zoonotic mutations.

Real-time FPGA prototyping of a 15GBaud SP-16QAM coherent optical receiver with optimal interpolating for clock recovery and equalization.

We demonstrate a real-time coherent optical receiver based on a single field programmable gate array (FPGA) chip. To strike the balance between the performance and hardware resources, we use a clock recovery scheme using the optimal interpolation (OI). The performance and complexity of the OI-based scheme and the traditional schemes are compared and discussed via offline digital signal processing. And a real-time 15GBaud single-polarization 16QAM transmission experiment under different received optical power using the FPGA-based receiver is carried out to demonstrate the overall performance of different clock recovery and equalization schemes. The result proves that, compared to the traditional scheme with a cubic interpolator and a 7-tap equalizer, the optimal interpolator significantly lowers the utilization of LUT, CARRY8, and DSP48 by 35%, 50%, and 11%, respectively, and can work properly under a received optical power of -40dBm.

Swine MicroRNAs ssc-miR-221-3p and ssc-miR-222 Restrict the Cross-Species Infection of Avian Influenza Virus.

Avian influenza virus (AIV) can cross species barriers to infect humans and other mammals. However, these species-cross transmissions are most often dead-end infections due to host restriction. Current research about host restriction focuses mainly on the barriers of cell membrane, nuclear envelope, and host proteins; whether microRNAs (miRNAs) play a role in host restriction is largely unknown. In this study, we used porcine alveolar macrophage (PAM) cells as a model to elucidate the role of miRNAs in host range restriction. During AIV infection, 40 dysregulation expressed miRNAs were selected in PAM cells. Among them, two Sus scrofa (ssc; swine) miRNAs, ssc-miR-221-3p and ssc-miR-222, could inhibit the infection and replication of AIV in PAM cells by directly targeting viral genome and inducing cell apoptosis via inhibiting the expression of anti-apoptotic protein HMBOX1. Avian but not swine influenza virus caused upregulated expressions of ssc-miR-221-3p and ssc-miR-222 in PAM cells. We further found that NF-κB P65 was more effectively phosphorylated upon AIV infection and that P65 functioned as a transcription activator to regulate the AIV-induced expression of miR-221-3p/222 Importantly, we found that ssc-miR-221-3p and ssc-miR-222 could also be specifically upregulated upon AIV infection in newborn pig tracheal epithelial (NPTr) cells and also exerted anti-AIV function. In summary, our study indicated that miRNAs act as a host barrier during cross-species infection of influenza A virus.IMPORTANCE The host range of an influenza A virus is determined by species-specific interactions between virus and host cell factors. Host miRNAs can regulate influenza A virus replication; however, the role of miRNAs in host species specificity is unclear. Here, we show that the induced expression of ssc-miR-221-3p and ssc-miR-222 in swine cells is modulated by NF-κB P65 phosphorylation in response to AIV infection but not swine influenza virus infection. ssc-miR-221-3p and ssc-miR-222 exerted antiviral function via targeting viral RNAs and causing apoptosis by inhibiting the expression of HMBOX1 in host cells. These findings uncover miRNAs as a host range restriction factor that limits cross-species infection of influenza A virus.

Investigation of the low-complexity Hilbert FIR filter enhanced 112-Gbit/s SSB 16-QAM transmission with parallelized Kramers-Kronig reception over 1440-km SSMF.

The Hilbert transform links the log-magnitude and the phase of the field modulated signals as long as the minimum phase condition is satisfied in the Kramer-Kronig (KK) receiver. In discrete-time signal processing, the Hilbert transform is generally replaced by a finite impulse response (FIR) filter to reduce the computational complexity, that is the so-called Hilbert transform FIR (HT-FIR) filter. The performance of the HT-FIR filter is extremely important, as the in-band flatness, the ripple, the group delay, the Gibbs phenomenon, and the edge effect, which indeed impair the phase retrieval. Hence, we investigate four different HT-FIR filter schemes that are in the form of type III and type IV based on the frequency-domain (FD) sampling approach and the time-domain (TD) windowing function approach. Also, we analyze the performance for each filter under different digital upsampling scenarios and conclude that a trade-off between the reduced inter-symbol-interference (ISI) and the Gibbs phenomenon is essential to obtain an optimal sampling rate and an improved KK performance when the HT-FIR filter with a short length is adopted. The results show that the FD-based HT-FIR filter can relax the upsampling requirement while having a better in-band flatness and a lower edge effect. The experiment is conducted in the parallelized block-wise KK reception-based 112-Gbit/s SSB 16-QAM optical transmission system over a 1920-km cascaded Raman fiber amplifier (RFA) link to investigate the limit transmission performance of the practical KK receiver. The experimental results show that when the transmission distance is up to 1440-km, the BER of the FD-based HT-FIR filter can be lower than the soft decision-forward error correction (SD-FEC) threshold of 2 × 10-2 with only 3 samples per symbol (3-SPS) upsampling rate and 8 non-integer tap coefficients are used, while other TD-based HT-FIR filter schemes with a BER lower than the SD-FEC threshold require at least 4-SPS upsampling rate.

Transmission of a 112-Gbit/s 16-QAM over a 1440-km SSMF with parallel Kramers-Kronig receivers enabled by an overlap approach and bandwidth compensation.

We investigate the parallelized performance of the conventional Kramers-Kronig (KK) and without the digital up-sampling KK (WDU-KK) receivers in a 112-Gbit/s 16-ary quadrature amplitude modulation (16-QAM) system over a 1440-km standard single-mode fiber (SSMF). A joint overlap approach and bandwidth compensation filter (OLA-BC) architecture is presented to mitigate the edge effect caused by the Hilbert transform and the Gibbs phenomenon induced by the FIR filter, respectively. Moreover, the computational complexity of the OLA-BC based parallelized KK/WDU-KK receiver is also discussed. Parallelized KK/WDU-KK receivers based on the presented OLA-BC architecture can effectively mitigate the edge effect and the Gibbs phenomenon together with more than two orders of magnitude improvement in terms of bit-error-ratio (BER) compared with parallelized KK/WDU-KK receivers without OLA-BC receivers in back-to-back (B2B) case. Finally, we successfully transmit the 16-QAM signals over 960-km SSMF with a BER lower than 7% hard-decision forward error correction (HD-FEC) threshold (3.8 × 10-3) and 1440-km SSMF with a BER lower than 20% soft-decision FEC (SD-FEC) threshold (2 × 10-2).

Prevailing I292V PB2 mutation in avian influenza H9N2 virus increases viral polymerase function and attenuates IFN-ß induction in human cells.

Adaptation of PB2 protein is important for the establishment of avian influenza viruses in mammalian hosts. Here, we identify I292V as the prevalent mutation in PB2 of circulating avian H9N2 and pandemic H1N1 viruses. The same dominant PB2 mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses. In human cells, PB2-292V in H9N2 virus has the combined ability of conferring higher viral polymerase activity and stronger attenuation of IFN-ß induction than that of its predecessor PB2-292I. IFN-ß attenuation is accompanied by higher binding affinity of PB2-292V for host mitochondrial antiviral signalling protein, an important intermediary protein in the induction of IFN-ß. In the mouse in vivo model, PB2-292V mutation increases H9N2 virus replication with ensuing increase in disease severity. Collectively, PB2-292V is a new mammalian adaptive marker that promotes H9N2 virus replication in mammalian hosts with the potential to improve transmission from birds to humans.

Research on the effect and mechanism of antimicrobial peptides HPRP-A1/A2 work against Toxoplasma gondii infection.

With increasing antibiotic resistance and drug safety concerns, novel therapeutics are urgently needed. Antimicrobial peptides are promising candidates that could address the spread of multidrug-resistant pathogens. HPRP-A1/A2 are known to display antimicrobial activity against gram-negative bacteria, gram-positive bacteria and some pathogenic fungi, but whether HPRP-A1/A2 work on Toxoplasma gondii (T gondii) is unknown. In this study, we found that the viability of tachyzoites that received HPRP-A1/A2 treatment was significantly decreased, and there was a reduction in the adhesion to and invasion of macrophages by tachyzoites after HPRP-A1/A2 treatment. HPRP-A1/A2 damaged the integrity of tachyzoite membranes, as characterized by membrane disorganization in and cytoplasm outflow from tachyzoites. In addition, in vivo injection with HPRP-A1/A2 resulted in a significantly decreased number of tachyzoites and an accelerated Th1/Tc1 response, and elicited pro-inflammatory cytokines in T gondii-infected mice. Furthermore, HPRP-A1/A2-treated splenocytes exhibited a significantly increased Tc1/Th1 response, and HPRP-A1/A2-stimulated macrophages inhibited the growth of carboxyfluorescein succinimidyl amino ester (CFSE)-labelled tachyzoites, which had higher TNF-α/IL-12 mRNA levels. Altogether, these results imply that HPRP-A1/A2 are effective against T gondii through damaging the structure of tachyzoites and inducing a protective immune response, which could offer an alternative approach against T gondii infection.

Simulated annealing based hybrid forecast for improving daily municipal solid waste generation prediction.

A simulated annealing (SA) based variable weighted forecast model is proposed to combine and weigh local chaotic model, artificial neural network (ANN), and partial least square support vector machine (PLS-SVM) to build a more accurate forecast model. The hybrid model was built and multistep ahead prediction ability was tested based on daily MSW generation data from Seattle, Washington, the United States. The hybrid forecast model was proved to produce more accurate and reliable results and to degrade less in longer predictions than three individual models. The average one-week step ahead prediction has been raised from 11.21% (chaotic model), 12.93% (ANN), and 12.94% (PLS-SVM) to 9.38%. Five-week average has been raised from 13.02% (chaotic model), 15.69% (ANN), and 15.92% (PLS-SVM) to 11.27%.

A Multistep Chaotic Model for Municipal Solid Waste Generation Prediction.

In this study, a univariate local chaotic model is proposed to make one-step and multistep forecasts for daily municipal solid waste (MSW) generation in Seattle, Washington. For MSW generation prediction with long history data, this forecasting model was created based on a nonlinear dynamic method called phase-space reconstruction. Compared with other nonlinear predictive models, such as artificial neural network (ANN) and partial least square-support vector machine (PLS-SVM), and a commonly used linear seasonal autoregressive integrated moving average (sARIMA) model, this method has demonstrated better prediction accuracy from 1-step ahead prediction to 14-step ahead prediction assessed by both mean absolute percentage error (MAPE) and root mean square error (RMSE). Max error, MAPE, and RMSE show that chaotic models were more reliable than the other three models. As chaotic models do not involve random walk, their performance does not vary while ANN and PLS-SVM make different forecasts in each trial. Moreover, this chaotic model was less time consuming than ANN and PLS-SVM models.

BDIS-SLAM: a lightweight CPU-based dense stereo SLAM for surgery.

PURPOSE: Common dense stereo simultaneous localization and mapping (SLAM) approaches in minimally invasive surgery (MIS) require high-end parallel computational resources for real-time implementation. Yet, it is not always feasible since the computational resources should be allocated to other tasks like segmentation, detection, and tracking. To solve the problem of limited parallel computational power, this research aims at a lightweight dense stereo SLAM system that works on a single-core CPU and achieves real-time performance (more than 30 Hz in typical scenarios). METHODS: A new dense stereo mapping module is integrated with the ORB-SLAM2 system and named BDIS-SLAM. Our new dense stereo mapping module includes stereo matching and 3D dense depth mosaic methods. Stereo matching is achieved with the recently proposed CPU-level real-time matching algorithm Bayesian Dense Inverse Searching (BDIS). A BDIS-based shape recovery and a depth mosaic strategy are integrated as a new thread and coupled with the backbone ORB-SLAM2 system for real-time stereo shape recovery. RESULTS: Experiments on in vivo data sets show that BDIS-SLAM runs at over 30 Hz speed on modern single-core CPU in typical endoscopy/colonoscopy scenarios. BDIS-SLAM only consumes around an additional 12 % time compared with the backbone ORB-SLAM2. Although our lightweight BDIS-SLAM simplifies the process by ignoring deformation and fusion procedures, it can provide a usable dense mapping for modern MIS on computationally constrained devices. CONCLUSION: The proposed BDIS-SLAM is a lightweight stereo dense SLAM system for MIS. It achieves 30 Hz on a modern single-core CPU in typical endoscopy/colonoscopy scenarios (image size around 640 × 480 ). BDIS-SLAM provides a low-cost solution for dense mapping in MIS and has the potential to be applied in surgical robots and AR systems. Code is available at https://github.com/JingweiSong/BDIS-SLAM .

Recapitulation of the Powassan virus life cycle in cell culture.

Powassan virus (POWV) is a tick-borne flavivirus known for causing fatal neuroinvasive diseases in humans. Recently, there has been a noticeable increase in POWV infections, emphasizing the urgency of understanding viral replication, pathogenesis, and developing interventions. Notably, there are no approved vaccines or therapeutics for POWV, and its classification as a biosafety level-3 (BSL-3) agent hampers research. To overcome these obstacles, we developed a replicon system, a self-replicating RNA lacking structural proteins, making it safe to operate in a BSL-2 environment. We constructed a POWV replicon carrying the Gaussia luciferase (Gluc) reporter gene and blasticidin (BSD) selectable marker. Continuous BSD selection led to obtain a stable POWV replicon-carrying Huh7 cell lines. We identified cell culture adaptive mutations G4079A, G4944T and G6256A, resulting in NS2AR195K, NS3G122G, and NS3V560M, enhancing RNA replication. We demonstrated the utility of the POWV replicon system for high-throughput screening (HTS) assay to identify promising antivirals against POWV replication. We further explored the applications of the POWV replicon system, generating single-round infectious particles (SRIPs) by transfecting Huh7-POWV replicon cells with plasmids encoding viral capsid (C), premembrane (prM), and envelope (E) proteins, and revealed the distinct antigenic profiles of POWV with ZIKV. In summary, the POWV replicon and SRIP systems represent crucial platforms for genetic and functional analysis of the POWV life cycle and facilitating the discovery of antiviral drugs.IMPORTANCEIn light of the recent surge in human infections caused by POWV, a biosafety level-3 (BSL-3) classified virus, there is a pressing need to understand the viral life cycle and the development of effective countermeasures. To address this, we have pioneered the establishment of a POWV RNA replicon system and a replicon-based POWV SRIP system. Importantly, these systems are operable in BSL-2 laboratories, enabling comprehensive investigations into the viral life cycle and facilitating antiviral screening. In summary, these useful tools are poised to advance our understanding of the POWV life cycle and expedite the development of antiviral interventions.

Fine-scale population structure of the northern hard clam (Mercenaria mercenaria) revealed by genome-wide SNP markers.

Aquaculture is growing rapidly worldwide, and sustainability is dependent on an understanding of current genetic variation and levels of connectivity among populations. Genetic data are essential to mitigate the genetic and ecological impacts of aquaculture on wild populations and guard against unintended human-induced loss of intraspecific diversity in aquacultured lines. Impacts of disregarding genetics can include loss of diversity within and between populations and disruption of local adaptation patterns, which can lead to a decrease in fitness. The northern hard clam, Mercenaria mercenaria (Linnaeus, 1758), is an economically valuable aquaculture species along the North American Atlantic and Gulf coasts. Hard clams have a pelagic larval phase that allows for dispersal, but the level of genetic connectivity among geographic areas is not well understood. To better inform the establishment of site-appropriate aquaculture brood stocks, this study used DArTseq™ genotyping by sequencing to characterize the genetic stock structure of wild clams sampled along the east coast of North America and document genetic diversity within populations. Samples were collected from 15 locations from Prince Edward Island, Canada, to South Carolina, USA. Stringent data filtering resulted in 4960 single nucleotide polymorphisms from 448 individuals. Five genetic breaks separating six genetically distinct populations were identified: Canada, Maine, Massachusetts, Mid-Atlantic, Chesapeake Bay, and the Carolinas (F ST 0.003-0.046; p < 0.0001). This is the first study to assess population genetic structure of this economically important hard clam along a large portion of its native range with high-resolution genomic markers, enabling identification of previously unrecognized population structure. Results of this study not only broaden insight into the factors shaping the current distribution of M. mercenaria but also reveal the genetic population dynamics of a species with a long pelagic larval dispersal period along the North American Atlantic and Gulf coasts.

SARS-CoV-2 main protease cleaves MAGED2 to antagonize host antiviral defense.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent causing the global pandemic of COVID-19. SARS-CoV-2 genome encodes a main protease (nsp5, also called Mpro) and a papain-like protease (nsp3, also called PLpro), which are responsible for processing viral polyproteins to assemble a functional replicase complex. In this study, we found that Mpro of SARS-CoV-2 can cleave human MAGED2 and other mammalian orthologs at Gln-263. Moreover, SARS-CoV and MERS-CoV Mpro can also cleave human MAGED2, suggesting MAGED2 cleavage by Mpro is an evolutionarily conserved mechanism of coronavirus infection in mammals. Intriguingly, Mpro from Beta variant cleaves MAGED2 more efficiently than wild type, but Omicron Mpro is opposite. Further studies show that MAGED2 inhibits SARS-CoV-2 infection at viral replication step. Mechanistically, MAGED2 is associated with SARS-CoV-2 nucleocapsid protein through its N-terminal region in an RNA-dependent manner, and this disrupts the interaction between SARS-CoV-2 nucleocapsid protein and viral genome, thus inhibiting viral replication. When MAGED2 is cleaved by Mpro, the N-terminal of MAGED2 will translocate into the nucleus, and the truncated MAGED2 is unable to suppress SARS-CoV-2 replication. This work not only discovers the antiviral function of MAGED2 but also provides new insights into how SARS-CoV-2 Mpro antagonizes host antiviral response. IMPORTANCE Host factors that restrict severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain elusive. Here, we found that MAGED2 can be cleaved by SARS-CoV-2 main protease (Mpro) at Gln-263. SARS-CoV and MERS-CoV Mpro can also cleave MAGED2, and MAGED2 from multiple species can be cleaved by SARS-CoV-2 Mpro. Mpro from Beta variant cleaves MAGED2 more efficiently efficiently than wild type, but Omicron is the opposite. MAGED2 depletion enhances SARS-CoV-2 infection, suggesting its inhibitory role in SARS-CoV-2 infection. Mechanistically, MAGED2 restricts SARS-CoV-2 replication by disrupting the interaction between nucleocapsid and viral genomes. When MAGED2 is cleaved, its N-terminal will translocate into the nucleus. In this way, Mpro relieves MAGED2' inhibition on viral replication. This study improves our understanding of complex viral-host interaction and provides novel targets to treat SARS-CoV-2 infection.