Host Network Research Articles

Интеграция чужеродного генетического материала провоцирует локальный мутагенез в геноме бактерии-реципиента

An exchange with genetic information is one of the key factors driving bacterial evolution. However, the mechanisms for integration of horizontally transferred genes into the regulatory network of a new host remain almost unexplored so far. The present work aimed to investigate this adaptive process, specifically, involvement of the transcription machinery of bacterial cells. Two foreign genes in the genome of Escherichia coli K12 MG1655 were substituted with their copies from the genomes of predicted donors, and a long-term evolution experiment was initiated for both mutant and control cultures. After 2000 (for the sfmA gene) and 4000 (for the ydhZ gene) generations, modified and native genomic regions were amplified and used for population sequencing. Spontaneous mutations were analyzed, and it was found that substitutions of G/C- to A/T-pairs occurred more frequently in the modified regions as compared to non-modified, whereas A/T → G/C substitutions occurred more rarely. That means that the host genome responds to integration of foreign genetic material with an adaptive reaction aimed to enrich the modified region with A/T-pairs. In the course of long-term evolution, it may result either in “silencing” of an unfavourable gene with a specific suppressor of foreign genes, H-NS, or in creation of a promoter acceptable for adequate expression as a part of promoter island.

ChemInform Abstract: Host—Guest Chemistry in Two‐Dimensional Supramolecular Networks

AbstractReview: 119 refs.

Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus.

Diverse pathogenic agents often utilize overlapping host networks, and hub proteins within these networks represent attractive targets for broad-spectrum drugs. Using bacterial toxins, we describe a new approach for discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pathways. This approach can be widely used, as it combines genetic-based target identification with cell survival-based and protein function-based multiplex drug screens, and concurrently discovers therapeutic compounds and their protein targets. Using B-lymphoblastoid cells derived from the HapMap Project cohort of persons of African, European, and Asian ancestry we identified host caspases as hub proteins that mediate the lethality of multiple pathogenic agents. We discovered that an approved drug, Bithionol, inhibits host caspases and also reduces the detrimental effects of anthrax lethal toxin, diphtheria toxin, cholera toxin, Pseudomonas aeruginosa exotoxin A, Botulinum neurotoxin, ricin, and Zika virus. Our study reveals the practicality of identifying host proteins that mediate multiple disease pathways and discovering broad-spectrum therapies that target these hub proteins.

The status of molybdenum ions in the lead dioxide-lead glasses and vitroceramics

Glasses and vitroceramics in the xMoO3·(100−x)[4PbO2·Pb] system with x=5-50mol% MoO3 were prepared by melt quenching method. The influence of MoO3 content on optical properties and structure of the 4PbO2·Pb host network was investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman, photofluorescence and X-ray photoelectron (XPS) spectroscopies. The X-ray patterns show the presence of a small amount of Pb2MoO5 crystalline phase in the sample with x=40mol% MoO3. By increasing of MoO3 content up to 50mol% MoO3, Pb2MoO5 and tetragonal PbO crystalline phases were detected.Raman data show the bending modes of the OPbO linkages which allow the intercalation of [PbO4] structural units, isolated [MoO4] and deformed [MoO6] structural units as basic structural units formed by lead and molybdenum atoms.The photofluorescence spectroscopy data shows the transitions of Mo+5 and Pb2+ ions. According to the XPS data, the vitroceramic network contains mainly [MoO4] tetrahedral units and small amounts of [MoO6] octahedral units.

The Structure Modification of Substrate for Alloying Materials in Li-Ion Secondary Battery

Li-ion secondary batteries possessing high energy and power density have been extensively researched to satisfy the needs for large-scale vehicles and storage system [1]. Graphite, most commercially used these days, has a stable cycle behavior during the charge/discharge process, however, it shows a relatively low specific capacity (372 mAh/g). Much as the intercalation materials including graphite can react with Li ion reversibly, they have a low specific capacity because of the host network structure. In general, the materials that experience a conversion and alloying reaction with Li ion during the charge/discharge process show high energy density [2]. The alloying materials such as Si (4200 mAh/g for Li4.4Si), Sn (994 mAh/g for Li4.4Sn), and Sb (660 mAh/g for Li3Sb) have a much higher energy density compared to the conventional graphite electrode, and thus the development of negative electrode with the aforementioned elements should be the most reliable approach to achieve high energy density [3,4].Recently, Si has been extensively studied owing to its highest theoretical capacity among the negative electrode materials. Furthermore, Si is very inexpensive, easy to handle, and low electrochemical potential, with respect to Li metal. Besides, Sn has been also investigated as a high energy material. However, many researches have been addressing the critical issue of Si and Sn, leading to severe volume change during the charge/discharge process. The volume change is up to ~400% for Li4.4Si and Li4.4Sn, and it finally pulverizes and exfoliates Si and Sn from the current collector. In the last decade, many approaches have been made to overcome the critical issues of Si and Sn material [5]. The structural modification of substrate, which enlarge the surface area of active materials, could be an effective way to reduce the stress induced during the charge/discharge cycle. The substrate is able to maintain its initial structure and consistently affects active materials.In this study, we attempted to make micrometer-size modification of the substrate structure in sawtooth and pyramidal shape and nanometer-size modification in nanowire structure. The microelectromechanical systems (MEMS) allowed us to fabricate the sawtooth-shape (width of 85 and 170 μm, S-85 and S-170, respectively) and pyramidal-shape (50 and 100 μm, P-50 and P-100, respectively) Si wafer substrateas shown in Figure 1(a). The deposited Si film was verified by the cross-sectional FE-SEM analysis as shown in Figure 1(b). We also prepared nanowire structure on Cu foil. Figure 2 shows the surface images of nanowire structure and Sn-electrodeposited nanowire.In this presentation, we studied the electrochemical properties and the changes in the electrode surface according with the existence of structure modification. We sought to correlate the capacity retentions and the surface coverage of Si on the electrode. By confirming the regions in which the majority of the Si remained, the relaxation effect was verified. Moreover, the capacity retention and rate capability of the Sn electrodeposited nanowire electrode were also investigated by electrochemical analysis.

Short and Intermediate Range Ordering in Fast Cation Glasses for Battery Applications

Lithium batteries provide the highest energy density which makes them ideal candidates for future generations of portable electronics (laptops, cellular, tablets, etc.) and hybrid electric vehicles for the time being. However, the increasing demand for lithium batteries will be limited by the fact that lithium is not an abundant material and its cost is expected to increase considerably in the coming years. In contrast, sodium resources are unlimited (fourth most abundant element in Earth’s crust) and from economic point of view, sodium batteries appear as good alternative to lithium devices, particularly for large-scale stationary applications. The ionic conductivity of chalcogenide and chalcohalide glasses is 2 to 3 orders of magnitude higher than that of oxide glasses with the same mobile ion content. This makes chalcogenide systems suitable for applications in power rechargeable systems. Our studies are focused on the development of new Na+ion-conducting chalcohalide glasses combining sodium halides and sulfide-based glass network. Cation local environment and intermediate-range ordering in glasses are critically important to achieve fast ionic conduction. Usual structural hypothesis related to superionic glasses containing metal halides MY = LiI, NaBr, AgI, etc., implies the absence of chemical interactions between the host glass and metal halide. An expansion of the host network caused by large anions (I, Br) and related increase of the available free volume for fast cations, forming preferential conduction pathways, was considered to be the key parameter for glassy superionics. Nevertheless, recent studies of AgY and CuY crystalline coordination polymers show chemical interaction between metal halide and chalcogenide backbone giving rise to mixed M-centered polyhedra. The polyhedral connectivity was also found to be different, starting from isolated units and dimers and finishing by chains, 2D layers and tubes. Some characteristic types of MY-subnetwork are given in Fig. 1(a,b). Using pulsed neutron and high-energy x-ray diffraction combined with Reverse Monte Carlo modelling, we examine cation local and intermediate range ordering in two glassy systems containing either silver iodide or sodium halides. Sodium chalcogenide glasses exhibit high ionic conductivity and seem to be promising for battery applications. Figure 1

Fast-flux hunter: a system for filtering online fast-flux botnet

Fast-flux networks is a domain name system (DNS) technique used by botnets, which is hiding some attack like phishing and malware delivery sites behind associate dynamical network of compromised hosts acting as proxies, that sometimes hosts malicious content. Detection of fast-flux networks continues to be a difficult issue attributable to the similar behavior between these networks and alternative legitimate infrastructures, like server farms and content distribution networks. This study seeks to improve the detection and prediction of the unknown “zero-day” online fast-flux botnet. This improvement will be achieved using a new system called the fast-flux hunter (FFH), which supports a new adaptive evolving fuzzy neural network algorithm. The FFH system is a hybrid between the supervised and unsupervised online knowledge-based learning systems. The core mechanism of the FFH is based on the inherent feature of the fast-flux networks. It uses a collection of DNS traffic information. The FFH is able to scan over 7615 domain records and extract 14 distinct features for each domain. The FFH decreases the classification method’s error rate. The FFH has a detection accuracy rate of approximately 98 % and is compatible with life-long learning systems, footprint-consuming memory, and high-speed systems.

Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection.

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical diagnostic tools to distinguish between acute viral and bacterial respiratory infections is critical to improve patient care and limit the overuse of antibiotics in the medical community. The identification of prognostic respiratory virus biomarkers provides an early warning system that is capable of predicting which subjects will become symptomatic to expand our medical diagnostic capabilities and treatment options for acute infectious diseases. The host response to acute infection may be viewed as a deterministic signaling network responsible for maintaining the health of the host organism. We identify pathway signatures that reflect the very earliest perturbations in the host response to acute infection. These pathways provide a monitor the health state of the host using anomaly detection to quantify and predict health outcomes to pathogens.

An Improved Model for Analysis of Host Network Vulnerability

An Improved Model for Analysis of Host Network Vulnerability

Generation of new compounds through unbalanced transcription of landomycin A cluster.

The biosynthetically well-studied landomycin A cluster has been used to demonstrate the unbalancing of gene transcription as an efficient method for the generation of new compounds. Landomycin A structural genes were decoupled from the native regulators LanI and LanK and placed under the control of a single synthetic promoter and expressed in a heterologous host Streptomyces albus J1074. In contrast to their native quantitative and temporal regulation, these genes were transcribed as a single polycistronic mRNA leading to the production of four novel and two known compounds. No glycosylated landomycins were detected though the entire biosynthetic cluster was transcribed, showing the crucial role of the balanced gene expression for the production of landomycin A. Two new compounds, fridamycin F and G, isolated in this study were shown to originate from the interplay between the expressed biosynthetic pathway and metabolic network of the heterologous host. Structure activity studies of the isolated compounds as well as results of transcriptome sequencing are discussed in this article.

HOST LOCATION KNOWLEDGE SOURCING AND SUBSIDIARY INNOVATIVE PERFORMANCE — EXAMINING THE MODERATING ROLE OF ALTERNATIVE SOURCES OF KNOWLEDGE AND IPR DISTANCE

This study investigates the relationship between the subsidiary’s external knowledge sourcing in the host network of operation and innovative performance, and the moderating role of (i) alternative sources of knowledge (those related to the internal and external home knowledge network) and (ii) Intellectual Property Rights (IPRs) distance between the host and the home location of the Multinational Enterprise (MNE). Based on a dataset comprising 170 R&D subsidiaries (classified by 57 parent companies and 23 host countries) it is shown that a curvilinear (inverted U-shaped) relationship exists between external host knowledge sourcing and innovative performance. In terms of the moderating effects, the findings reveal that the influence of alternative sources of knowledge affects the aforementioned relationship in a negative way. Finally, a stronger IPR protection regime in the host location weakens, rather than strengthens the relationship between the external host knowledge sourcing and innovative performance.

Synaptic integration of transplanted interneuron progenitor cells into native cortical networks.

Interneuron-based cell transplantation is a powerful method to modify network function in a variety of neurological disorders, including epilepsy. Whether new interneurons integrate into native neural networks in a subtype-specific manner is not well understood, and the therapeutic mechanisms underlying interneuron-based cell therapy, including the role of synaptic inhibition, are debated. In this study, we tested subtype-specific integration of transplanted interneurons using acute cortical brain slices and visualized patch-clamp recordings to measure excitatory synaptic inputs, intrinsic properties, and inhibitory synaptic outputs. Fluorescently labeled progenitor cells from the embryonic medial ganglionic eminence (MGE) were used for transplantation. At 5 wk after transplantation, MGE-derived parvalbumin-positive (PV+) interneurons received excitatory synaptic inputs, exhibited mature interneuron firing properties, and made functional synaptic inhibitory connections to native pyramidal cells that were comparable to those of native PV+ interneurons. These findings demonstrate that MGE-derived PV+ interneurons functionally integrate into subtype-appropriate physiological niches within host networks following transplantation.

Two novel cation-induced supramolecular polymers with 2-3D polymeric cuprous thiocyanate frameworks: Synthesis, characterization and photocatalytic activities for the degradation of organic dye contaminants

In order to systematically explore the photocatalytic activity of the inorganic–organic supramolecular polymers induced by 1,1′-(1,n-alkylidene)bis[4-methylpyridinium] (n=1–2) cations, two novel cation-induced compounds, {(bmpm) [Cu2(SCN)4]}n (bmpm=1,1′-methylenebis[4-methylpyridinium] (1) and {(bmpe) [Cu2(SCN)4]}n (bmpe=1,1′-(1,2-ethanediyl)bis[4-methylpyridinium] (2) were obtained and characterized by X-ray crystallography. Compound 1 has a 3D framework with the cations trapped within host network cavities. Compound 2 possesses an infinite 2D supramolecular polypseudorotaxane structure linked by bridging thiocyanate groups. The third-order NLO, optical band gaps and photocatalytic activities of 1 and 2 were also evaluated. Remarkably, both 1 and 2 exhibited good photocatalytic abilities.

Efficient Synthesis of Ir-Polyoxometalate Cluster Using a Continuous Flow Apparatus and STM Investigation of Its Coassembly Behavior on HOPG Surface.

Taking advantage of a continuous-flow apparatus, the iridium(III)-containing polytungstate cluster K12Na2H2[Ir2Cl8P2W20O72]·37H2O (1) was obtained in a reasonable yield (13% based on IrCl3·H2O). Compound 1 was characterized by Fourier transform IR, UV-visible, (31)P NMR, electrospray ionization mass spectrometry (ESI-MS), and thermogravimetric analysis measurements. (31)P NMR, ESI-MS, and elemental analysis all indicated 1 was a new polytungstate cluster compared with the reported K14[(IrCl4)KP2W20O72] compound. Intriguingly, the successful isolation of 1 relied on the custom-built flow apparatus, demonstrating the uniqueness of continuous-flow chemistry to achieve crystalline materials. The catalytic properties of 1 were assessed by investigating the activity on catalyzing the electro-oxidation of ruthenium tris-2,2'-bipyridine [Ru(bpy)3](2+/3+). The voltammetric behavior suggested a coupled catalytic behavior between [Ru(bpy)3](3+/2+) and 1. Furthermore, on the highly oriented pyrolytic graphite surface, 1,3,5-tris(10-carboxydecyloxy) benzene (TCDB) was used as the two-dimensional host network to coassemble cluster 1; the surface morphology was observed by scanning tunneling microscope technique. "S"-shape of 1 was observed, indicating that the cluster could be accommodated in the cavity formed by two TCDB host molecules, leading to a TCDB/cluster binary structure.

West Nile virus infection in the Collaborative Cross mouse model recapitulates unique human disease states

Abstract West Nile Virus (WNV) is a cytopathic neurotropic flavivirus that causes a wide range of infection states in humans, ranging from asymptomatic to severe neuroinvasive disease. This variation supports the idea that host genetics play an important role in immunity to WNV infection. The significant individual to individual variation in immune responses within the human population can not be fully captured in single laboratory inbred strains, so a systems genetic approach requires the use of the Collaborative Cross (CC) mouse system to identify polymorphic host genes and networks that control the regulation of adaptive immunity to WNV infection. The CC is a panel of lines with over 40 million single nucleotide polymorphisms evenly distributed throughout the genome, providing the statistical power to map multiple genetic factors with small to moderate effect. In the CC model we have identified lines with unique human phenotypes that have not previously been captured in laboratory inbred strains, such as severe neuroinvasive disease and chronic WNV infection. Our use of the CC model shows differing immune responses to WNV in terms of T cell frequency and activation, antigen-specific CD8 T cell frequency, memory precursor cells, and T cell cytokine production between CC strains after WNV infection. A distinct immune signature is present in the chronic line, characterized by a strong systemic regulatory T cell response and late virus-specific response in the CNS due to viral persistence. Microarray analysis on spleen and CNS tissue reveals expression changes correlated with extreme immune phenotype responses within and between organ compartments, allowing for identification of correlates of protection and susceptibility to WNV infection.

Flexible Self-Assembled Molecular Templates on Graphene

We report on molecular self-assembly employing a host–guest architecture to pattern the growth of molecules on graphene model surface. Under suitable conditions, the 1,3,5-benzenetribenzoic acid (BTB) self-assembles into an extended honeycomb mesh on graphene on Ir(111), with the molecules in the network being stabilized by linear hydrogen bonds between the carboxylic groups. The nanopores of the mesh are used to host and govern the assembly of cobalt phthalocyanine (CoPC) guest molecules. We characterize the assembled structures structurally and electronically using low-temperature scanning tunneling microscopy (STM) and density functional theory (DFT) calculations. At a coverage higher than one CoPc per pore, the flexible hydrogen bonds of the host network undergo stretching to accommodate two CoPCs in a single pore. When the pores are uniformly doubly occupied, the guest molecules arrange into a herringbone pattern. This minimizes the energy cost associated with the stretching and twisting of the hydrogen bonds between the BTB molecules. The phenomenon observed here can be used to tailor molecular assemblies on graphene to controllably modify its properties. In addition, it allows the formation of guest monomers and dimers stabilized mechanically on the surface of graphene, an archetypical weakly interacting substrate.

AP1S3 is required for hepatitis C virus infection by stabilizing E2 protein

Hepatitis C virus (HCV) infects 130 million people worldwide and is a leading cause of liver cirrhosis, end-stage liver disease and hepatocellular carcinoma. The interactions between viral elements and host factors play critical role on HCV invade, replication and release. Here, we identified adaptor protein complex 1 sigma 3 subunit (AP1S3) as a dependency factor for the efficient HCV infection in hepatoma cells. AP1S3 silencing in cultivated Huh7.5.1 cells significantly reduced the production of HCV progeny particles. Immunoprecipitation analysis revealed that AP1S3 interacted with the HCV E2 protein. With this interaction, AP1S3 could protect HCV E2 from ubiquitin-mediated proteasomal degradation. Using in vivo ubiquitylation assay, we identified that E6-Associated Protein (E6AP) was associated with HCV E2. In addition, treatment with synthetic peptide that contains the AP1S3-recognized motif inhibited HCV infection in Huh7.5.1 cells. Our data reveal AP1 as a novel host network that is required by viruses during infection and provides a potential target for developing broad-spectrum anti-virus strategies.

Composition patterns and network structure of epiphyte–host interactions in Chilean and New Zealand temperate forests

ABSTRACTEcological networks are becoming increasingly used as a framework to study epiphyte–host interactions. However, efforts to quantify the properties of epiphyte–host networks have produced inconsistent results. Epiphyte–host interactions in New Zealand and Chilean temperate forests were quantified to test for non-random patterns in nestedness, negative co-occurrences, number of links, and network specialisation. Results showed that three out of five New Zealand networks were significantly more nested than null model expectations, compared with just one out of four Chilean networks. Epiphytes co-occurred more often than null model expectations in one New Zealand network and one in Chile. In all cases, the number of links maintained by each epiphyte and host species was consistent with null model expectations. Lastly, two New Zealand networks and one in southern Chile were significantly less specialised than null model expectations, with all remaining networks returning low specialisation scores. As such, aside from the tendency for greater nestedness in New Zealand networks, most epiphyte species were distributed on their host trees at random. We attribute the result of nestedness in New Zealand to the abundance of large nest epiphytes (Astelia spp. in particular), which may facilitate the sequential colonisation of epiphyte species on developing host trees. The lack of negative co-occurrences suggests that negative species interactions are not an important determinant of species assemblage structure. Low network specialisation scores suggest that epiphytes are selecting for specific host traits, rather than specific host species for colonisation.

A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host-Pathogen Interaction Networks.

Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host–pathogen dynamic interaction networks. The consideration of host–pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host–pathogen molecular interaction networks, and consequent inferences of the host–pathogen relationship could be translated into biomedical applications.

Structural Collapse of the Hydroquinone-Formic Acid Clathrate: A Pressure-Medium-Dependent Phase Transition.

The energy landscape governing a new pressure-induced phase transition in the hydroquinone-formic acid clathrate is reported in which the host structure collapses, opening up the cavity channels within which the guest molecules migrate and order. The reversible isosymmetric phase transition causes significant changes in the morphology and the birefringence of the crystal. The subtle intermolecular interaction energies in the clathrate are quantified at varying pressures using novel model energies and energy frameworks. These calculations show that the high-pressure phase forms a more stable host network at the expense of less-stable host-guest interactions. The phase transition can be kinetically hindered using a nonhydrostatic pressure-transmitting medium, enabling the comparison of intermolecular energies in two polymorphic structures in the same pressure range. Overall this study illustrates a need for accurate intermolecular energies when analyzing self-assembly structures and supramolecular aggregates.