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.     

Moderate lameness leads to marked behavioral changes in dairy cows

Lameness is one of the most prevalent diseases affecting the welfare of cows in modern dairy production. Lameness leads to behavioral changes in severely lame cows, which have been investigated in much detail. For early detection of lameness, knowledge of the effects of moderate lameness on cow behavior is crucial. Therefore, the behavior of nonlame and moderately lame cows was compared on 17 Swiss dairy farms. On each farm, 5 to 11 nonlame (locomotion score 1 of 5) and 2 to 7 moderately lame (locomotion score 3 of 5) cows were selected for data collection in two 48-h periods (A, B) separated by an interval of 6 to 10 wk. Based on visual locomotion scoring, 142 nonlame and 66 moderately lame cows were examined in period A and 128 nonlame and 53 moderately lame cows in period B. Between these 2 periods, the cows underwent corrective hoof trimming. Lying behavior, locomotor activity, and neck activity were recorded by accelerometers (MSR145 data logger, MSR Electronics GmbH, Seuzach, Switzerland), and feeding and rumination behaviors by noseband sensors (RumiWatch halter, ITIN + HOCH GmbH, Liestal, Switzerland). Furthermore, visits to the brush and the concentrate feeder, and the milking order position were recorded. In comparison with nonlame cows, moderately lame cows had a longer lying duration, a longer average lying bout duration, and a greater lateral asymmetry in lying duration. Average locomotor activity, locomotor activity during 1 h after feed delivery or push-ups, and average neck activity were lower in moderately lame cows. Eating time and the number of eating chews (jaw movements) were reduced in moderately lame compared with nonlame cows, whereas no effect of moderate lameness was evident for ruminating time, number of ruminating chews and boluses, and average number of ruminating chews per bolus. Moderately lame cows visited the concentrate feeder and the brush less frequently, and they were further back in the milking order compared with nonlame cows. In conclusion, nonlame and moderately lame cows differed in a biologically relevant way in many of the behavioral variables investigated in this study. Therefore, the use of these behavioral changes seems to be promising to develop a tool for early lameness detection.     

Mitochondrial and cytosolic branched-chain amino acid transaminases from yeast, homologs of the myc oncogene-regulated Eca39 protein

We have isolated a high copy suppressor of a temperature-sensitive mutation in ATM1, which codes for an ABC transporter of Saccharomyces cerevisiae mitochondria. The suppressor, termed BAT1, encodes a protein of 393 amino acid residues with an NH2-terminal extension that directs Bat1p to the mitochondrial matrix. A highly homologous protein, Bat2p, of 376 amino acid residues was found in the cytosol. Both Bat proteins show striking similarity to the mammalian protein Eca39, which is one of the few known targets of the myc oncogene. Deletion of a single BAT gene did not impair growth of yeast cells. In contrast, deletion of both genes resulted in an auxotrophy for branched-chain amino acids (Ile, Leu, and Val) and in a severe growth reduction on glucose-containing media, even after supply of these amino acids. Mitochondria and cytosol isolated from bat1 and bat2 deletion mutants, respectively, contained largely reduced activities for the conversion of branched-chain 2-ketoacids to their corresponding amino acids. Thus, the Bat proteins represent the first known isoforms of yeast branched-chain amino acid transaminases. The severe growth defect of the double deletion mutant observed even in the presence of branched-chain amino acids suggests that the Bat proteins, in addition to the supply of these amino acids, perform another important function in the cell.     

Comment and discussion on digital processing of PD pulses

Some of the more salient aspects of the digital processing technology of PD signals are examined. Most of the efforts in this field are concentrated on the application of digital analyzers for pulse height analysis, pattern recognition and identification of the physical phenomena. It is demonstrated that errors in the signal processing unit can lead to dominant mistakes in the interpretation of the test results     

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.     

Introduction

Concluding remarks With this brief exposition of the areas covered in this special double issue on Eurotra, we shall now conclude our introduction. We hope that the volume will achieve its goals, as outlined above, at least to some extent. Certainly, much more could be said about a wide range of topics which have been covered in the lifetime or the project so far. For instance, these article, mainly written by linguists, deliberately neglect the software implementation and environment aspects of the prototype Eurotra Translation System, as well as a number of peripheral tools and components of the system that are available to the user, such as lexical data bases, text-handling mechanisms and the like. The reader interested in aspects of this kind is referred to Raw et al. 1989 for a very brief introduction, and to the Eurotra software team at the Commission of the European Communities (DG XIII, Luxembourg) for more details. However, one goal that we do hope to come close to achieving is to give a fair overview of the Eurotra linguistic theory of translation and the mainstream and sideline formalisms expressing variant versions of it. If we have come anywhere near achieving that, our gratitude is due to the numerous Eurotra colleagues who have supported us in preparing this volume, and to the editor of this journal.     

Study of the beta -delayed neutron decay of 18N

The shortage of suitable liver donors for children has motivated the use of ABO-incompatible (ABO-I) grafts for transplantation in urgent situations. However, survival after ABO-I liver grafts has been reported at about 30% as compared with 80% in cases of ABO-identical or -compatible liver grafts. This difference has been attributed to antibody-mediated, hyperacute or chronic liver rejection, due to preformed ABO antibodies (alloantibodies). In this study, we report our results with ABO-I livers in children without alloantibodies at the time of transplantation. From January 1988 to June 1993, 143 OLT were performed in 122 children. Eight children received 8 ABO-I liver grafts. Of these, 7 patients were included in the study. All 7 were alloantibody free before OLT. Five children were spontaneously alloantibody free, while in 2 children, the plasma alloantibodies were eliminated before and after transplantation using intravenous infusion of specific blood group antigens of the donor blood group (soluble antigens). Immunosuppression consisted of a triple-drug treatment combining CsA, AZA, and steroids. The follow-up period was between 10 and 48 months. One child died from a surgical complication. Six children survived, but 1 died 10 months later from intestinal obstruction. There were no graft losses and no episodes of hyperacute or chronic rejection. The graft and patient survival rate was 71%. There was a 28% incidence of rejection, but all were mild (requiring steroid boluses only). Our results suggest that the absence of ABO alloantibodies at the time of and after transplantation can protect ABO-I liver grafts against antibody-mediated rejection, whether hyperacute or chronic, and that soluble antigens are effective in eliminating alloantibodies in children.     

Neutron Scattering and Ordering of Nuclear Spins

The ordering of nuclear spins takes place at extremely low temperatures because of the weakness of the interactions between their magnetic moments. Neutron scattering is the traditional and unique method to study the collective ordering of magnetic moments. The combination of the problem (nuclear spin ordering) and the method (neutron scattering) leads to new insight into the many body behaviour of the nuclear spin system and into some of the long standing general questions of the cooperative behaviour of magnetic systems. We describe neutron scattering studies on the nuclear spin systems in Cu and Ag at nano- and subnanokelvin temperatures as an example of a very successful international collaboration based on the work performed at the Low Temperature Laboratory, in the Helsinki University of Technology in Otaniemi. The collaboration was initiated by Olli V. Lounasmaa.