Electrode switch-an efficient induced approach for self-activation of an electrode toward water splitting.

In this paper, we provide a novel electrode switch (ES) method to improve the stability of the alkaline electrolyzer toward water splitting. The voltage of the alkaline electrolyzer consisting of commercial Ni mesh electrodes utilizing the ES mode exhibits extreme stability because highly active Ni oxide(hydroxide) with oxygen defects is in situ formed during the hydrogen evolution reaction (HER) polarization process.

The global nitrogen regulator GlnR is a direct transcriptional repressor of the key gluconeogenic gene pckA in actinomycetes.

In most actinomycetes, GlnR governs both nitrogen and non-nitrogen metabolisms (e.g., carbon, phosphate, and secondary metabolisms). Although GlnR has been recognized as a global regulator, its regulatory role in central carbon metabolism [e.g., glycolysis, gluconeogenesis, and the tricarboxylic acid (TCA) cycle] is largely unknown. In this study, we characterized GlnR as a direct transcriptional repressor of the pckA gene that encodes phosphoenolpyruvate carboxykinase, catalyzing the conversion of the TCA cycle intermediate oxaloacetate to phosphoenolpyruvate, a key step in gluconeogenesis. Through the transcriptomic and quantitative real-time PCR analyses, we first showed that the pckA transcription was upregulated in the glnR null mutant of Amycolatopsis mediterranei. Next, we proved that the pckA gene was essential for A. mediterranei gluconeogenesis when the TCA cycle intermediate was used as a sole carbon source. Furthermore, with the employment of the electrophoretic mobility shift assay and DNase I footprinting assay, we revealed that GlnR was able to specifically bind to the pckA promoter region from both A. mediterranei and two other representative actinomycetes (Streptomyces coelicolor and Mycobacterium smegmatis). Therefore, our data suggest that GlnR may repress pckA transcription in actinomycetes, which highlights the global regulatory role of GlnR in both nitrogen and central carbon metabolisms in response to environmental nutrient stresses. IMPORTANCE: The GlnR regulator of actinomycetes controls nitrogen metabolism genes and many other genes involved in carbon, phosphate, and secondary metabolisms. Currently, the known GlnR-regulated genes in carbon metabolism are involved in the transport of carbon sources, the assimilation of short-chain fatty acid, and the 2-methylcitrate cycle, although little is known about the relationship between GlnR and the TCA cycle and gluconeogenesis. Here, based on the biochemical and genetic results, we identified GlnR as a direct transcriptional repressor of pckA, the gene that encodes phosphoenolpyruvate carboxykinase, a key enzyme for gluconeogenesis, thus highlighting that GlnR plays a central and complex role for dynamic orchestration of cellular carbon, nitrogen, and phosphate fluxes and bioactive secondary metabolites in actinomycetes to adapt to changing surroundings.

YWHAH, a member of 14-3-3 family proteins, and PSME2, the proteasome activator subunit 2, are key host factors of Japanese encephalitis virus infection.

BACKGROUND: Host response to virus infection is key to the effective control and eventual elimination of viruses or infected cells; however, the underlying mechanism of Japanese encephalitis virus (JEV) infection remains unclear. METHODS: In the present study, short time-series expression was analyzed by R software to obtain two groups of differentially expressed genes (DEGs) [upregulated/downregulated] during the entire process of JEV infection based on the data in the Gene Expression Omnibus database. GO enrichment and KEGG pathway, protein interactions and hub genes selection were analyzed by DAVID, STRING and Cytoscape respectively. Interactions of the JEV and host proteins, and the microRNAs that target Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activating protein Eta (YWHAH) and Proteasome activator subunit 2(PSME2) were predicted by P-hipster and ENCORI, respectively. Expression levels of YWHAH and PSME2 were analyzed using the HPA database and RT-qPCR assay. RESULTS: Two groups of continuously changed DEGs during entire process of JEV infection were obtained. Continuously upregulated cluster was mainly related to regulation of transcription, immune response and inflammatory response; and the continuous downregulated group mainly including intracellular protein transport and signal transduction, several proteolysis pathways. As targets of several microRNAs, the downregulated-YWHAH and the upregulated-PSME2 were related to host and JEV proteins to affect several pathways after JEV infection. CONCLUSIONS: YWHAH and PSME2 are key host factors of JEV infection based on their continuously differentially expressed pattern, interactions with multiple JEV proteins, and as members of the hub genes. Our results provide valuable information for further studies on the interactions between viruses and host.

The Community Coevolution Model with Application to the Study of Evolutionary Relationships between Genes Based on Phylogenetic Profiles.

Organismal traits can evolve in a coordinated way, with correlated patterns of gains and losses reflecting important evolutionary associations. Discovering these associations can reveal important information about the functional and ecological linkages among traits. Phylogenetic profiles treat individual genes as traits distributed across sets of genomes and can provide a fine-grained view of the genetic underpinnings of evolutionary processes in a set of genomes. Phylogenetic profiling has been used to identify genes that are functionally linked and to identify common patterns of lateral gene transfer in microorganisms. However, comparative analysis of phylogenetic profiles and other trait distributions should take into account the phylogenetic relationships among the organisms under consideration. Here, we propose the Community Coevolution Model (CCM), a new coevolutionary model to analyze the evolutionary associations among traits, with a focus on phylogenetic profiles. In the CCM, traits are considered to evolve as a community with interactions, and the transition rate for each trait depends on the current states of other traits. Surpassing other comparative methods for pairwise trait analysis, CCM has the additional advantage of being able to examine multiple traits as a community to reveal more dependency relationships. We also develop a simulation procedure to generate phylogenetic profiles with correlated evolutionary patterns that can be used as benchmark data for evaluation purposes. A simulation study demonstrates that CCM is more accurate than other methods including the Jaccard Index and three tree-aware methods. The parameterization of CCM makes the interpretation of the relations between genes more direct, which leads to Darwin's scenario being identified easily based on the estimated parameters. We show that CCM is more efficient and fits real data better than other methods resulting in higher likelihood scores with fewer parameters. An examination of 3786 phylogenetic profiles across a set of 659 bacterial genomes highlights linkages between genes with common functions, including many patterns that would not have been identified under a nonphylogenetic model of common distribution. We also applied the CCM to 44 proteins in the well-studied Mitochondrial Respiratory Complex I and recovered associations that mapped well onto the structural associations that exist in the complex. [Coevolution; evolutionary rates; gene network; graphical models; phylogenetic profiles; phylogeny.].

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To explore whether there is an interaction between melatonin (MT) and calcium (Ca2+) in regulating heat tolerance of plants, we analyzed the response of endogenous MT and Ca2+ to heat stress, and examined the effect of MT and Ca2+ on the reactive oxygen (ROS) accumulation, antioxidant system, and transcripts of heat shock factor (HSF) and heat shock proteins (HSPs) of cucumber seedlings under high temperature stress. Seedlings were foliar sprayed with 100 µmol·L-1 MT, 10 mmol·L-1 CaCl2, 3 mmol·L-1 ethylene glycol tetraacetic acid (EGTA, Ca2+ chelating agent) +100 µmol·L-1 MT, 0.05 mmol·L-1 chlorpromazine (calmodulin antagonist, CPZ) +100 µmol·L-1 MT, 100 µmol·L-1 p-chlorophenylalanine (p-CPA, inhibitor of MT) +10 mmol·L-1 CaCl2 or deionized water (H2O), respectively. The results showed that both endogenous MT and Ca2+ in cucumber seedlings were induced by high temperature stress. The seedlings treated with exogenous MT showed significant increases in the mRNA expression of calmodulin (CaM), calcium-dependent protein kinase (CDPK5), calcineurin B-like protein (CBL3) and CBL interacting protein kinase (CIPK2) compared with the control at normal temperature. The mRNA levels of tryptophane decarboxylase (TDC), 5-hydroxytryptamine-N-acetyltransferase (SNAT) and N-acetyl-5-hydroxytryptamine methyltransferase (ASMT), key genes of MT biosynthesis and endogenous MT content were also induced by Ca2+ in cucumber seedlings. Exogenous MT and CaCl2 alleviated the heat-induced oxidative damage through increasing antioxidant ability, reducing the accumulation of reactive oxygen species (ROS), and upregulating the mRNA abundances of HSF7, HSP70.1 and HSP70.11, as evidenced by mild thermal damage symptoms, lower heat injury index and electrolyte leakage under heat stress. The positive effect of MT-induced antioxidant capacity and mRNA expression of HSPs was removed by adding EGTA and CPZ in stressed seedlings. Similarly, the mitigating role of Ca2+ in the peroxidation damage to high temperature stress was reversed by p-CPA. These results suggested that both MT and Ca2+ could induce heat tolerance of cucumber seedlings, which had crosstalk in the process of heat stress signal transduction.

Reconfigurable add-drop filter based on an antisymmetric multimode photonic crystal nanobeam cavity in a silicon waveguide.

We have designed and demonstrated a reconfigurable channel add-drop filter (ADF) based on an antisymmetric multimode photonic crystal nanobeam cavity (AM-PCNC) in a silicon waveguide. The proposed AM-PCNC can realize channel add-drop filtering by selectively filtering and reflecting the fundamental mode (TE0) and 1st-order mode (TE1) in the multimode waveguide. A high-performance add-drop filter has been demonstrated with a high extinction ratio of 28.2 dB and an insertion loss of 0.18 dB. Meanwhile, the reconfigurable add-dropping has been realized by heating the nanobeam cavity to tune the filtering wavelength. A tuning efficiency of 0.464 nm/mW was measured. The rising and falling time are ∼6.5 µs and ∼0.6 µs, respectively, which are at microsecond time scale. The footprint of the involved nanobeam cavity is only 16.5 µm2. The device can potentially provide an integrated component for optical switch array, routers, and wavelength-division multiplexing in the optical networks.

Exploring the mobilome and resistome of Enterococcus faecium in a One Health context across two continents.

Enterococcus faecium is a ubiquitous opportunistic pathogen that is exhibiting increasing levels of antimicrobial resistance (AMR). Many of the genes that confer resistance and pathogenic functions are localized on mobile genetic elements (MGEs), which facilitate their transfer between lineages. Here, features including resistance determinants, virulence factors and MGEs were profiled in a set of 1273 E. faecium genomes from two disparate geographic locations (in the UK and Canada) from a range of agricultural, clinical and associated habitats. Neither lineages of E. faecium, type A and B, nor MGEs are constrained by geographic proximity, but our results show evidence of a strong association of many profiled genes and MGEs with habitat. Many features were associated with a group of clinical and municipal wastewater genomes that are likely forming a new human-associated ecotype within type A. The evolutionary dynamics of E. faecium make it a highly versatile emerging pathogen, and its ability to acquire, transmit and lose features presents a high risk for the emergence of new pathogenic variants and novel resistance combinations. This study provides a workflow for MGE-centric surveillance of AMR in Enterococcus that can be adapted to other pathogens.

Image Classification Method Based on Multi-Agent Reinforcement Learning for Defects Detection for Casting.

A casting image classification method based on multi-agent reinforcement learning is proposed in this paper to solve the problem of casting defects detection. To reduce the detection time, each agent observes only a small part of the image and can move freely on the image to judge the result together. In the proposed method, the convolutional neural network is used to extract the local observation features, and the hidden state of the gated recurrent unit is used for message transmission between different agents. Each agent acts in a decentralized manner based on its own observations. All agents work together to determine the image type and update the parameters of the models by the stochastic gradient descent method. The new method maintains high accuracy. Meanwhile, the computational time can be significantly reduced to only one fifth of that of the GhostNet.

High-performance waveguide Ge/Si avalanche photodiode with a lateral separate-absorption-charge-multiplication structure.

A high-performance waveguide Ge/Si avalanche photodiode operating at the O-band (1310 nm) is designed with a Ge/Si ridge waveguide defined by two shallow trenches in the active region and fabricated with simplified processes. The device shows a high primary responsivity of 0.96 A/W at the unit-gain voltage of -7.5 V. It has a large 3-dB bandwidth of >27 GHz and a low dark current of 1.8 µA at a reverse bias voltage of -13 V. When the present Ge/Si APD is used for receiving 25 Gbps data, the eye-diagram is open even for an optical power as low as -18 dBm. Furthermore, 50 Gbps data receiving is also demonstrated with an input optical power of -15 dBm, showing the great potential of the present Ge/Si APD for the application in future high-speed data transmission systems.

Non-rigid registration of medical images based on [Formula: see text] non-tensor product B-spline.

In this study, a non-tensor product B-spline algorithm is applied to the search space of the registration process, and a new method of image non-rigid registration is proposed. The tensor product B-spline is a function defined in the two directions of x and y, while the non-tensor product B-spline [Formula: see text] is defined in four directions on the 2-type triangulation. For certain problems, using non-tensor product B-splines to describe the non-rigid deformation of an image can more accurately extract the four-directional information of the image, thereby describing the global or local non-rigid deformation of the image in more directions. Indeed, it provides a method to solve the problem of image deformation in multiple directions. In addition, the region of interest of medical images is irregular, and usually no value exists on the boundary triangle. The value of the basis function of the non-tensor product B-spline on the boundary triangle is only 0. The algorithm process is optimized. The algorithm performs completely automatic non-rigid registration of computed tomography and magnetic resonance imaging images of patients. In particular, this study compares the performance of the proposed algorithm with the tensor product B-spline registration algorithm. The results elucidate that the proposed algorithm clearly improves the accuracy.

Nitric Oxide Functions as a Downstream Signal for Melatonin-Induced Cold Tolerance in Cucumber Seedlings.

Melatonin (MT) and nitric oxide (NO) are two multifunctional signaling molecules that are involved in the response of plants to abiotic stresses. However, how MT and NO synergize in response to cold stress affecting plants is still not clear. In this study, we found that endogenous MT accumulation under cold stress was positively correlated with cold tolerance in different varieties of cucumber seedlings. The data presented here also provide evidence that endogenous NO is involved in the response to cold stress. About 100 µM MT significantly increased the nitrate reductase (NR) activity, NR-relative messenger RNA (mRNA) expression, and endogenous NO accumulation in cucumber seedlings. However, 75 µM sodium nitroprusside (SNP, a NO donor) showed no significant effect on the relative mRNA expression of tryptophan decarboxylase (TDC), tryptamine-5-hydroxylase (T5H), serotonin-N-acetyltransferase (SNAT), or acetylserotonin O-methyltransferase (ASMT), the key genes for MT synthesis and endogenous MT levels. Compared with H2O treatment, both MT and SNP decreased electrolyte leakage (EL), malondialdehyde (MDA), and reactive oxygen species (ROS) accumulation by activating the antioxidant system and consequently mitigated cold damage in cucumber seedlings. MT and SNP also enhanced photosynthetic carbon assimilation, which was mainly attributed to an increase in the activity and mRNA expression of the key enzymes in the Calvin-Benson cycle. Simultaneously, MT- and SNP-induced photoprotection for both photosystem II (PSII) and photosystem I (PSI) in cucumber seedlings, by stimulating the PsbA (D1) protein repair pathway and ferredoxin-mediated NADP+ photoreduction, respectively. Moreover, exogenous MT and SNP markedly upregulated the expression of chilling response genes, such as inducer of CBF expression (ICE1), C-repeat-binding factor (CBF1), and cold-responsive (COR47). MT-induced cold tolerance was suppressed by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO, a specific scavenger of NO). However, p-chlorophenylalanine (p-CPA, a MT synthesis inhibitor) did not affect NO-induced cold tolerance. Thus, novel results suggest that NO acts as a downstream signal in the MT-induced plant tolerance to cold stress.

Silicon/2D-material photodetectors: from near-infrared to mid-infrared.

Two-dimensional materials (2DMs) have been used widely in constructing photodetectors (PDs) because of their advantages in flexible integration and ultrabroad operation wavelength range. Specifically, 2DM PDs on silicon have attracted much attention because silicon microelectronics and silicon photonics have been developed successfully for many applications. 2DM PDs meet the imperious demand of silicon photonics on low-cost, high-performance, and broadband photodetection. In this work, a review is given for the recent progresses of Si/2DM PDs working in the wavelength band from near-infrared to mid-infrared, which are attractive for many applications. The operation mechanisms and the device configurations are summarized in the first part. The waveguide-integrated PDs and the surface-illuminated PDs are then reviewed in details, respectively. The discussion and outlook for 2DM PDs on silicon are finally given.

Systemic analysis of the expression levels and prognosis of breast cancer-related cadherins.

Cadherins form connection between cells, facilitate communication, and serve as essential agents in the progression of multiple cancers. Over 100 cadherins have been identified and they are mainly divided into four groups: classical cadherins (CDHs), protocadherins (PCDHs), desmosomal (DSC), and cadherin-related proteins. Accumulating evidence has indicated that several members of the cadherins are involved in breast cancer development. Nevertheless, the expression profiles and corresponding prognostic outcomes of these breast cancer-related cadherins are yet to be analyzed. Here, we examined the expression levels and prognostic potential of these breast cancer-related cadherins from the specific databases viz. oncomine, gene expression profiling interactive analysis, human protein atlas, UALCAN, Kaplan-Meier Plotter, and cBioPortal. We found that the CDH2/11 levels were higher in breast cancer tissues, compared to healthy breast tissues, whereas with CDH3-5, PCDH8/10, and DSC3, the levels were lower in the former than in the latter. Additionally, for CDH1/6/13/17/23, PCDH7, and FAT4, trancript level alterations between breast cancer and healthy tissues varied across different databases. The CDH1 protein levels were elevated in breast cancer tissues versus healthy breast tissues, whereas the protein levels of CDH3/11 and PCDH8/10 were reduced in breast cancer, compared to healthy breast tissues. For CDH15 and CDH23, the expression levels paralleled tumor stage. Survival analysis, using the Kaplan-Meier Plotter database, demonstrated that elevated CDH1-3 levels correlated with diminished relapse-free survival in breast cancer patients. Alternately, enhanced CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 levels estimated a rise in relapse-free survival of breast cancer patients. These data suggest CDH1-3 to be a promising target for breast cancer precision therapy and CDH4-6/15/17/23, PCDH10, DSC3, and FAT4 to be novel biomarkers for breast cancer prognosis.

Synergistic Manipulation of Zn2+ Ion Flux and Desolvation Effect Enabled by Anodic Growth of a 3D ZnF2 Matrix for Long-Lifespan and Dendrite-Free Zn Metal Anodes.

Aqueous rechargeable Zn metal batteries have attracted widespread attention due to the intrinsic high volumetric capacity, low cost, and high safety. However, the low Coulombic efficiency and limited lifespan of Zn metal anodes resulting from uncontrollable growth of Zn dendrites impede their practical application. In this work, a 3D interconnected ZnF2 matrix is designed on the surface of Zn foil (Zn@ZnF2 ) through a simple and fast anodic growth method, serving as a multifunctional protective layer. The as-fabricated Zn@ZnF2 electrode can not only redistribute the Zn2+ ion flux, but also reduce the desolvation active energy significantly, leading to stable and facile Zn deposition kinetics. The results reveal that the Zn@ZnF2 electrode can effectively inhibit dendrites growth, restrain the hydrogen evolution reactions, and endow excellent plating/stripping reversibility. Accordingly, the Zn@ZnF2 electrode exhibits a long cycle life of over 800 h at 1 mA cm-2 with a capacity of 1.0 mAh cm-2 in a symmetrical cell test, the feasibility of which is also convincing in Zn@ZnF2 //MnO2 and Zn@ZnF2 //V2 O5 full batteries. Importantly, a hybrid zinc-ion capacitor of the Zn@ZnF2 //AC can work at an ultrahigh current density of ≈60 mA cm-2 for up to 5000 cycles with a high capacity retention of 92.8%.

Hybrid ultrathin-silicon/graphene waveguide photodetector with a loop mirror reflector.

Graphene has emerged as a promising solution for on-chip ultrafast photodetection for its advantages of easy integration, high mobility, adjustable chemical potential, and wide operation wavelength range. In order to realize high-performance photodetectors, it is very important to achieve efficient light absorption in the active region. In this work, a compact and high-speed hybrid silicon/graphene photodetector is proposed and demonstrated by utilizing an ultra-thin silicon photonic waveguide integrated with a loop mirror. With this design, the graphene absorption rate for the fundamental mode of TE polarization is improved by ∼5 times compared to that in the conventional hybrid silicon/graphene waveguide with hco=220 nm. One can achieve 80% light absorption ratio within the active-region length of only 20 µm for the present silicon/graphene waveguide photodetector at 1550 nm. For the fabricated device, the responsivity is about 25 mA/W under 0.3V bias voltage and the 3-dB bandwidth is about 17 GHz. It is expected to achieve very high bandwidth by introducing high-quality Al2O3 insulator layers and reducing the graphene channel length in the future.

Uniform Li Plating/Stripping within Ni Macropore Arrays Enabled by Regulated Electric Field Distribution for Ultra-Stable Li-Metal Anodes.

Although Li-metal anodes are extremely attractive owing to the ultrahigh theoretical specific capacity, the low Coulombic efficiency and severe safety hazards resulting from uncontrollable Li dendrites growth hinder their widespread implementation. Herein, we propose a novel design of Ni macropore arrays for the functional Li deposition host. Benefiting from the regulated electric field distribution, Li nucleation and growth can be well confined within conductive Ni macropores. Consequently, the Ni macropore array electrode exhibits stable Li deposition behavior, i.e., high Coulombic efficiency of above 97% over 400 cycles for 1.0 mAh cm-2. Most importantly, the LiFePO4 || Li-Ni macropore arrays full cell also shows greatly enhanced cycling stability (90.3 mAh g-1 at 1 C after 700 cycles), holding great promise for high-performance rechargeable Li metal batteries.

High-performance silicon-graphene hybrid plasmonic waveguide photodetectors beyond 1.55 µm.

Graphene has attracted much attention for the realization of high-speed photodetection for silicon photonics over a wide wavelength range. However, the reported fast graphene photodetectors mainly operate in the 1.55 µm wavelength band. In this work, we propose and realize high-performance waveguide photodetectors based on bolometric/photoconductive effects by introducing an ultrathin wide silicon-graphene hybrid plasmonic waveguide, which enables efficient light absorption in graphene at 1.55 µm and beyond. When operating at 2 µm, the present photodetector has a responsivity of ~70 mA/W and a setup-limited 3 dB bandwidth of >20 GHz. When operating at 1.55 µm, the present photodetector also works very well with a broad 3 dB bandwidth of >40 GHz (setup-limited) and a high responsivity of ~0.4 A/W even with a low bias voltage of -0.3 V. This work paves the way for achieving high-responsivity and high-speed silicon-graphene waveguide photodetection in the near/mid-infrared ranges, which has applications in optical communications, nonlinear photonics, and on-chip sensing.

Refining Interfaces between Electrolyte and Both Electrodes with Carbon Nanotube Paper for High-Loading Lithium-Sulfur Batteries.

Lithium sulfur (Li-S) batteries are appealing energy storage technologies because of their high theoretical energy density and low cost. However, Li-S batteries suffer from poor practical energy density due to serious polysulfide dissolution and shuttle, as well as lithium anode corrosion. Herein, we provide a dual-protection strategy for the high-energy-density Li-S cell by inserting two nanotube paper (CNTp) interlayers on both electrodes. The CNTp interlayers can provide stable interfaces for both the cathode and anode, facilitating the formation of uniform charge transfer and ion flue. As a result, the Li-S cell exhibits stable cycling performance and great rate ability up to a high rate of 5 C (5 C = 25 mA cm-2). Even at an ultrahigh sulfur load of 12.1 mg cm-2, a high areal capacity of 12.6 mAh cm-2 is still achieved, which can remain at 11.1 mAh cm-2 after 30 cycles (corresponding to 917 mAh g-1). The refined interfaces between the electrolyte and both electrodes are further confirmed by the micro-zone current distribution and COMSOL simulation. Our approach provides an effective and universal strategy to improve the electrochemical stability of the Li-S cell at high sulfur load, opening a new platform for designing advanced metal cell systems.

Effective inhibition of different Japanese encephalitis virus genotypes by RNA interference targeting two conserved viral gene sequences in vitro and in vivo.

Japanese encephalitis is a zoonotic, mosquito-borne, infectious disease caused by Japanese encephalitis virus (JEV), which is prevalent in China. At present, there are no specific drugs or therapies for JEV infection, which can only be treated symptomatically. Lentivirus-mediated RNA interference (RNAi) is a highly efficient method to silence target genes. In this study, two lentiviral shRNA, LV-C and LV-NS5, targeting the conserved viral gene sequences were used to inhibit different JEV genotypes strains in BHK21 cells and mice. The results showed that LV-C significantly inhibited JEV genotype I and genotype III strains in cells and mice. Quantitative RT-PCR analysis showed that JEV mRNA were reduced by 83.2-90.9% in cells by LV-C and that flow cytometry analysis confirmed the inhibitory activity of LV-C. The viral titers were reduced by about 1000-fold in cells and the brains of suckling mice by LV-C, and the pretreatment of LV-C protected 60-80% of mice against JEV-induced lethality. The inhibitory activities of LV-NS5 in cells and mice were weaker than those of LV-C. These results indicate that RNAi targeting of the two conserved viral gene sequences had significantly suppressed the replication of different JEV genotypes strains in vitro and in vivo, highlighting the feasibility of RNAi targeting of conserved viral gene sequences for controlling JEV infection.

Phylogenetic Clustering of Genes Reveals Shared Evolutionary Trajectories and Putative Gene Functions.

Homologous genes in prokaryotes can be described using phylogenetic profiles which summarize their patterns of presence or absence across a set of genomes. Phylogenetic profiles have been used for nearly twenty years to cluster genes based on measures such as the Euclidean distance between profile vectors. However, most approaches do not take into account the phylogenetic relationships amongst the profiled genomes, and overrepresentation of certain taxonomic groups (i.e., pathogenic species with many sequenced representatives) can skew the interpretation of profiles. We propose a new approach that uses a coevolutionary method defined by Pagel to account for the phylogenetic relationships amongst target organisms, and a hierarchical-clustering approach to define sets of genes with common distributions across the organisms. The clusters we obtain using our method show greater evidence of phylogenetic and functional clustering than a recently published approach based on hidden Markov models. Our clustering method identifies sets of amino-acid biosynthesis genes that constitute cohesive pathways, and motility/chemotaxis genes with common histories of descent and lateral gene transfer.