Identification of Host Cellular Protein Substrates of SARS-COV-2 Main Protease

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19) being associated with severe pneumonia. Like with other viruses, the interaction of SARS-CoV-2 with host cell proteins is necessary for successful replication, and cleavage of cellular targets by the viral protease also may contribute to the pathogenesis, but knowledge about the human proteins that are processed by the main protease (3CLpro) of SARS-CoV-2 is still limited. We tested the prediction potentials of two different in silico methods for the identification of SARS-CoV-2 3CLpro cleavage sites in human proteins. Short stretches of homologous host-pathogen protein sequences (SSHHPS) that are present in SARS-CoV-2 polyprotein and human proteins were identified using BLAST analysis, and the NetCorona 1.0 webserver was used to successfully predict cleavage sites, although this method was primarily developed for SARS-CoV. Human C-terminal-binding protein 1 (CTBP1) was found to be cleaved in vitro by SARS-CoV-2 3CLpro, the existence of the cleavage site was proved experimentally by using a His₆-MBP-mEYFP recombinant substrate containing the predicted target sequence. Our results highlight both potentials and limitations of the tested algorithms. The identification of candidate host substrates of 3CLpro may help better develop an understanding of the molecular mechanisms behind the replication and pathogenesis of SARS-CoV-2.     

Social environmental selection as a mediator of gender, ethnic, and personality effects on college student drinking.

Structural equation modeling was used to test the mediational role of social environmental selection on alcohol use in cross-sectional samples of 447 students from a rural state university and 421 students from an urban private university. Results showed that male gender, White ethnicity, and sensation seeking were uniquely associated with greater alcohol use. Mediational analyses indicated that socioenvironmental factors (i.e., Greek involvement, friends' approval of drinking/getting drunk) were positively associated with alcohol use and significantly accounted for parts of the effects of ethnicity and sensation seeking, but not gender, on alcohol use. Results suggest that White students and those high on sensation seeking may drink more heavily in college, in part because they select social environments in which alcohol use is encouraged. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A heuristic algorithm for distributed control in manufacturing systems

Distributed Problem Solving Networks (DPSN) provide a means for interconnecting intelligent problem solver nodes that can solve only a part of a problem depending on their ability in the problem domain. The decomposition of a problem into subproblems, and the selection of nodes to solve them can be regarded as the generation of an AND/OR tree, and the solution of the problem as a search for a solution tree. Introducing measurements for the cost of a solution tree, we present an algorithm to find one having minimal cost under certain conditions. A Flexible Manufacturing System consisting of a network of flexible workcells is used as an example.     

Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils

Neutrophil-mediated innate host defense mechanisms include pathogen elimination through bacterial phagocytosis, which activates the 5-lipoxygenase (5-LOX) product synthesis. Here, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs), which mimic the receptor-recognized sites of bacterial (CpG-ODNs) and genomic (G-rich ODNs) DNAs released from the inflammatory area, on the neutrophil functions after cell stimulation with Salmonella typhimurium. A possible mechanism for ODN recognition by Toll-like receptor 9 (TLR9) and RAGE receptor has been proposed. We found for the first time that the combination of the magic peptide LRR11 from the leucine-rich repeat (LRR) of TLR9 with the CpG-ODNs modulates the uptake and signaling from ODNs, in particular, dramatically stimulates 5-LOX pathway. Using thickness shear mode acoustic method, we confirmed the specific binding of CpG-ODNs, but not G-rich ODN, to LRR11. The RAGE receptor has been shown to play an important role in promoting ODN uptake. Thus, FPS-ZM1, a high-affinity RAGE inhibitor, suppresses the synthesis of 5-LOX products and reduces the uptake of ODNs by neutrophils; the inhibitor effect being abolished by the addition of LRR11. The results obtained revealed that the studied peptide-ODN complexes possess high biological activity and can be promising for the development of effective vaccine adjuvants and antimicrobial therapeutics.     

Lipid labeling with32P-orthophosphate and14C-acetate in marine copepods

Freshly collectedCalanus pacificus were maintained in sea water containing 25 μCi/ml [³²P]orthophosphate or 1 μCi/ml [¹⁴C]acetate at 10 C for 24 hr. The animals took up label from the environment and incorporated it into various lipid fractions. After incubation with [¹⁴C]acetate the order of specific activity of the different lipid classes was: phospholipids > free fatty acids > wax esters > triglycerides. Argentation thin layer chromatography of the fatty acid methyl esters showed that ca. 50% of the activity was in saturated fatty acids and 34% in polyunsaturated acids. When the animals were exposed to [³²P]orthophosphate, lysophosphatidyl choline became most heavily labeled, followed by lysophosphatidyl ethanolamine, sphingomyelin, phosphatidyl ethanolamine, and phosphatidyl choline. Comparison of the data obtained with those available for decapods and mammals revealed striking similarities between these phylogenetically distant groups. It is believed that labeling the lipids of marine and freshwater planktonic crustaceans in this way will provide much information about the metabolism of lipids in these organisms.     

Heterogeneous asymmetric reactions. 23. Enantioselective hydrogenation of ethyl pyruvate over cinchonine- and α-isocinchonine-modified platinum catalysts

The enantioselective hydrogenation of ethyl pyruvate to (S)-ethyl lactate over cinchonine- and -isocinchonine-modified Pt/Al₂O₃ catalysts was studied as a function of modifier concentration and reaction temperature. The maximum enantioselectivities obtained under the applied mild conditions were 89% ee using cinchonine (0.014 mmoldm^–3, 1 bar H₂, 23°C, 6% AcOH in toluene), and 76% ee in the case of -isocinchonine (0.14 mmoldm^–3, 1 bar H₂, –10°C, 6% AcOH in toluene). Since -isocinchonine of rigid structure exists only in anti-open conformation these data provide additional experimental evidence to support the former suggestion concerning the dominating role of anti-open conformation in these cinchona-modified enantioselective hydrogenations.     

Living carbocationic polymerization

Conventional cationic polymerization can be converted into living carbocationic polymerization (LC^⊕Pzn) by the introduction of common anion into the charge. Thus the conventional polymerization of isobutylene (IB) induced by the 2-chloro-2,4,4-trimethylpentane (TMPCl)/TiCl₄ combination yields LC^⊕Pzn of IB upon the addition of tetrabutyl ammonium chloride (n-Bu₄NCl), most likely due to then-Bu₄NCl+TiCl₄ ?n-Bu₄N^⊕+TiCl ₅ ^⊕ equilibrium. A kinetic model has been developed and tested which corroborates these propositions. By this model we have gained for the first time quantitative insight into the quasiliving equilibrium.     

An Interoperable Grid Information System for Integrated Resource Monitoring Based on Virtual Organizations

In many Grid infrastructures different kinds of information services are in use, which utilize different incompatible data structures and interfaces to encode and provide their data. Homogeneous monitoring of these infrastructures with the monitoring data being accessible everywhere independently of the middleware which provided it, is the basis for a consistent status reporting on the Grids’ resources and services. Thus, interoperability or interoperation between the different information services in a heterogeneous Grid infrastructure is required. Monitoring data must contain the identity of the affected Virtual Organization (VO) so that it can be related to the resources and services the VO has allocated to enable VO-specific information provision. This paper describes a distributed architecture for an interoperable information service, which combines data unification and categorization with policies for VO membership, VO resource management and data transformations. This service builds the basis for an integrated and interoperating monitoring of Grids, which provide their data to more than one VO and utilize heterogeneous information services.     

Effect of enzymatic degradation of chitosan in polyhydroxybutyrate/chitosan/calcium phosphate composites on in vitro osteoblast response

Polyhydroxybutyrate/chitosan/calcium phosphate composites are interesting biomaterials for utilization in regenerative medicine and they may by applied in reconstruction of deeper subchondral defects. Insufficient informations were found in recent papers about the influence of lysozyme degradation of chitosan in calcium phosphate/chitosan based composites on in vitro cytotoxicity and proliferation activity of osteoblasts. The effect of enzymatic chitosan degradation on osteoblasts proliferation was studied on composite films in which the porosity of origin 3D scaffolds was eliminated and the surface texture was modified. The significantly enhanced proliferation activity with faster population growth of osteoblasts were found on enzymatically degraded biopolymer composite films with α-tricalcium phosphate and nanohydroxyapatite. No cytotoxicity of composite films prepared from lysozyme degraded scaffolds containing a large fraction of low molecular weight chitosans (LMWC), was revealed after 10 days of cultivation. Contrary to above in the higher cytotoxicity origin untreated nanohydroxyapatite films and porous composite scaffolds. The results showed that the synergistic effect of surface distribution, morphology of nanohydroxyapatite particles, microtopography and the presence of LMWC due to chitosan degradation in composite films were responsible for compensation of the cytotoxicity of nanohydroxyapatite composite films or porous composite scaffolds.     

Scattering and space-charge effects in Wigner Monte Carlo simulations of single and double barrier devices

Transport in single and double barrier devices is studied using a Monte Carlo solver for the Wigner transport equation. This approach allows the effects of tunneling and scattering to be included. Several numerical methods have been improved to render the Wigner Monte Carlo technique more robust, including a newly developed particle annihilation algorithm. A self-consistent iteration scheme with the Poisson equation was introduced. The role of scattering and space charge effects on the electrical characteristics of n-i-n nanostructures, ultra-scaled double gate MOSFETs, and GaAs resonant tunneling diodes is demonstrated. An erratum to this article can be found at