scholarly journals Engineered influenza virions reveal the contributions of non-hemagglutinin structural proteins to vaccine mediated protection

2021 ◽  
Author(s):  
Zhaochen Luo ◽  
Alanson W. Girton ◽  
Brook E. Heaton ◽  
Nicholas S. Heaton

The development of improved and universal anti-influenza vaccines would represent a major advance in the protection of human health. In order to facilitate the development of such vaccines, understanding how viral proteins can contribute to protection from disease is critical. Much of the previous work to address these questions relied on reductionist systems (i.e. vaccinating with individual proteins or VLPs that contain only a few viral proteins); thus we have an incomplete understanding of how immunity to different subsets of viral proteins contribute to protection. Here, we report the development of a platform in which a single viral protein can be deleted from an authentic viral particle that retains the remaining full complement of structural proteins and viral RNA. As a first study with this system, we chose to delete the major IAV antigen, the hemagglutinin protein, to evaluate how the other components of the viral particle contribute en masse to protection from influenza disease. Our results show that while anti-HA immunity plays a major role in protection from challenge with a vaccine-matched strain, the contributions from other structural proteins were the major drivers of protection against highly antigenically drifted, homosubtypic strains. This work highlights the importance of evaluating the inclusion of non-HA viral proteins in the development of broadly efficacious and long-lasting influenza vaccines. Importance Influenza virus vaccines currently afford short-term protection from viruses that are closely related to the vaccine strains. There is currently much effort to develop improved, next-generation influenza vaccines that elicit broader and longer-lasting protection. While the hemagglutinin protein is the major viral antigen, in this work, we developed an approach with which to evaluate the contributions of the non-hemagglutinin proteins to vaccine mediated protection. Our results indicate that other structural proteins together may help to mediate broad antiviral protection and should be considered in the development of more universal influenza vaccines.

2021 ◽  
Author(s):  
Soichiro Kijima ◽  
Tom O. Delmont ◽  
Urara Miyazaki ◽  
Morgan Gaia ◽  
Hisashi Endo ◽  
...  

AbstractNucleocytoplasmic large DNA viruses (NCLDVs) infect diverse eukaryotes and form a group of viruses with capsids encapsulating large genomes. Recent studies are increasingly revealing a spectacular array of functions encoded in their genomes, including genes for energy metabolisms, nutrient uptake, as well as cytoskeleton. Here, we report the discovery of genes homologous to myosins, the major eukaryotic motor proteins previously unrecognized in the virosphere, in environmental genomes of NCLDVs from the surface of the oceans. Interestingly, these genes were often accompanied by kinesin genes in the environmental genomes, suggesting a role of these viral proteins in the intracellular viral particle transport. Phylogenetic analyses indicate that most viral myosins (named “virmyosins”) belong to the Imitervirales order, except for one belonging to the Phycodnaviridae family. On the one hand, the phylogenetic positions of virmyosin-encoding Imitervirales are scattered within the Imitervirales. On the other hand, Imitervirales virmyosin genes form a monophyletic group in the phylogeny of diverse myosin sequences. Furthermore, phylogenetic trends for the virmyosin genes and viruses containing them were incongruent. Based on these results, we argue that multiple transfers of myosin homologs have occurred not only from eukaryotes to viruses but also between viruses, supposedly during co-infections of the same host.


Author(s):  
Stefan Scherbaum ◽  
Simon Frisch ◽  
Maja Dshemuchadse

Abstract. Folk wisdom tells us that additional time to make a decision helps us to refrain from the first impulse to take the bird in the hand. However, the question why the time to decide plays an important role is still unanswered. Here we distinguish two explanations, one based on a bias in value accumulation that has to be overcome with time, the other based on cognitive control processes that need time to set in. In an intertemporal decision task, we use mouse tracking to study participants’ responses to options’ values and delays which were presented sequentially. We find that the information about options’ delays does indeed lead to an immediate bias that is controlled afterwards, matching the prediction of control processes needed to counter initial impulses. Hence, by using a dynamic measure, we provide insight into the processes underlying short-term oriented choices in intertemporal decision making.


2018 ◽  
pp. 49-68 ◽  
Author(s):  
M. E. Mamonov

Our analysis documents that the existence of hidden “holes” in the capital of not yet failed banks - while creating intertemporal pressure on the actual level of capital - leads to changing of maturity of loans supplied rather than to contracting of their volume. Long-term loans decrease, whereas short-term loans rise - and, what is most remarkably, by approximately the same amounts. Standardly, the higher the maturity of loans the higher the credit risk and, thus, the more loan loss reserves (LLP) banks are forced to create, increasing the pressure on capital. Banks that already hide “holes” in the capital, but have not yet faced with license withdrawal, must possess strong incentives to shorten the maturity of supplied loans. On the one hand, it raises the turnovers of LLP and facilitates the flexibility of capital management; on the other hand, it allows increasing the speed of shifting of attracted deposits to loans to related parties in domestic or foreign jurisdictions. This enlarges the potential size of ex post revealed “hole” in the capital and, therefore, allows us to assume that not every loan might be viewed as a good for the economy: excessive short-term and insufficient long-term loans can produce the source for future losses.


2019 ◽  
Vol 9 (1) ◽  
pp. 53-66 ◽  
Author(s):  
Dandan Irawan

Basically a natural partnership will achieve its goal if mutual requirements, mutual reinforcement, and mutual benefit can be maintained and made a strong fundamental commitment among partners. Nevertheless the development seems very slow. The cause is the presence of specific and different conditions and structure factors compared to other countries. Along with that, we still encounter various forms of gaps, such as inequality among regions, among income groups, between sectors, among economic actors, and so forth. The next problem is that in business entities including cooperatives and micro and small enterprises in running their business activities requires business partnerships with medium and large enterprises in order to improve business performance and business scale. While on the other hand our economic conditions and structures are not yet fully conducive to fostering partnerships based on purely business considerations or competitive market motivations but the business partnership of the foundation is strong enough in our country's constitution. Partnerships will work if partners are equally benefiting. Our concept of partnership is like that, although in the short term, there is a party or a party benefiting more from the other side.


1974 ◽  
Vol 77 (1) ◽  
pp. 64-70 ◽  
Author(s):  
Gustav Wägar

ABSTRACT Whether the short-term regulation of thyroidal protein synthesis by TSH occurs at the transcriptional or the translational level was tested by measuring the effect of actinomycin D (act D) on the TSH-induced stimulation of L-14C-leucine incorporation into the thyroidal proteins of rats. TSH was injected 6 h before the rats were killed. The thyroid glands were then removed and incubated in vitro in the presence of L-14C-leucine for 2 h. The pronounced stimulation of leucine incorporation in the TSH-treated animals was depressed as compared with controls but still significant even when the animals had been pre-treated with 100 μg act D 24 and 7 h before sacrifice. On the other hand, act D strongly decreased incorporation of 3H-uridine into RNA. Short-term regulation of thyroidal protein synthesis by TSH appears to be partly but not wholly dependent on neosynthesis of RNA. Hence regulation may partly occur at the translation level of protein synthesis.


2002 ◽  
Vol 13 (02) ◽  
pp. 072-082 ◽  
Author(s):  
Cynthia G. Fowler ◽  
Christopher D. Bauch ◽  
Wayne O. Olsen

The purpose of this study was to determine whether clicks presented in rarefaction or condensation modes produce more accurate diaghostic information. Subjects were 20 consecutive patients who were seen at the Mayo Clinic for unilateral acoustic neuromas. The nontumor ear served as a control to minimize intersubject variability in the latencies. A standard audio logic evaluation was followed by an auditory brainstem response (ABR) test for which the stimuli were rarefaction and condensation clicks. Responses were analyzed for the presence of waves I, III, and V; absolute latencies of waves I, III, and V; interpeak intervals I–III, III–V, and I–V; and interaurallatency difference for wave V. The results indicated that measures from both polarities were similar in this set of patients and that neither click polarity provided diagnostic advantages over the other. Recommendations are to collect ABRs to both click polarities individually to obtain the full complement of waves on which to base the diagnostic impression.


Sensors ◽  
2021 ◽  
Vol 21 (11) ◽  
pp. 3678
Author(s):  
Dongwon Lee ◽  
Minji Choi ◽  
Joohyun Lee

In this paper, we propose a prediction algorithm, the combination of Long Short-Term Memory (LSTM) and attention model, based on machine learning models to predict the vision coordinates when watching 360-degree videos in a Virtual Reality (VR) or Augmented Reality (AR) system. Predicting the vision coordinates while video streaming is important when the network condition is degraded. However, the traditional prediction models such as Moving Average (MA) and Autoregression Moving Average (ARMA) are linear so they cannot consider the nonlinear relationship. Therefore, machine learning models based on deep learning are recently used for nonlinear predictions. We use the Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU) neural network methods, originated in Recurrent Neural Networks (RNN), and predict the head position in the 360-degree videos. Therefore, we adopt the attention model to LSTM to make more accurate results. We also compare the performance of the proposed model with the other machine learning models such as Multi-Layer Perceptron (MLP) and RNN using the root mean squared error (RMSE) of predicted and real coordinates. We demonstrate that our model can predict the vision coordinates more accurately than the other models in various videos.


1982 ◽  
Vol 62 (4) ◽  
pp. 1199-1209 ◽  
Author(s):  
V. A. POUTEAUX ◽  
G. I. CHRISTISON ◽  
C. S. RHODES

Two experiments were conducted to evaluate the involvement of dietary protein and short-term chilling on the incidence of diarrhea and on transit time of digesta in pigs weaned at 3–4 wk of age. The three protein sources used were buttermilk powder (BMP), soybean meal (SBM) or pea protein concentrate (PPC), which provided 85% of the dietary protein. In exp. 1, 72 pigs were exposed to a 16 °C decrease in ambient temperature for 8 h on day 4 of a 9-day feeding trial; 72 pigs were not chilled. The pigs on the PPC diet gained less (539 g) (P < 0.05) than pigs on BMP (1183 g) or SBM (952 g) although intakes were similar. Neither diet nor chilling affected fecal moisture content or the incidence of diarrhea. The PPC ration increased (P < 0.05) transit time (slowed rate of passage) on day 8. Chilling on day 4 decreased (P < 0.05) transit time (18.7 vs. 25.6 h) on that day. Neither protein source nor chilling caused differences in total or coliform bacteria isolated from fecal samples on blood agar or MacConkey's agar. In exp. 2, eight chilled and nine control pigs were euthanized and the quantity of three markers in six segments of the gastrointestinal tract was determined. The PPC diet passed more slowly than the other diets. In chilled pigs, the chromic oxide front was closer to the anus, indicating an increased rate of passage. It was concluded that the severity of the cold exposure was not suffficient to induce diarrhea and that there was no interaction between the effects of chilling and of dietary protein. There was, however, a tendency for chilling to increase the rate of passage of digesta which could have an additive effect on the severity of nutritional diarrhea. Key words: Pigs, weaning, diarrhea, protein, cold, transit time.


2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Julia R. Lazzari-Dean ◽  
Anneliese M.M. Gest ◽  
Evan W. Miller

Membrane potential (Vmem) is a fundamental biophysical signal present in all cells. Vmem signals range in time from milliseconds to days, and they span lengths from microns to centimeters. Vmem affects many cellular processes, ranging from neurotransmitter release to cell cycle control to tissue patterning. However, existing tools are not suitable for Vmem quantification in many of these areas. In this review, we outline the diverse biology of Vmem, drafting a wish list of features for a Vmem sensing platform. We then use these guidelines to discuss electrode-based and optical platforms for interrogating Vmem. On the one hand, electrode-based strategies exhibit excellent quantification but are most effective in short-term, cellular recordings. On the other hand, optical strategies provide easier access to diverse samples but generally only detect relative changes in Vmem. By combining the respective strengths of these technologies, recent advances in optical quantification of absolute Vmem enable new inquiries into Vmem biology. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


PEDIATRICS ◽  
1994 ◽  
Vol 93 (2) ◽  
pp. 163-163
Author(s):  
Klaus Minde

The present article discusses developmental changes of aggression seen in preschool children and reports on an 18-month short-term prospective study of three preschool populations: a group referred for aggressive behavior problems, a normal control group, and a group of youngsters who had lived in violent homes, but showed no aggressive behaviors. Results indicate that the aggressive children, in comparison with the other two groups at age 4, showed a significant delay in their interpersonal awareness and perspective taking ability. However, although the aggressive children caught up with their peers in the course of the study period, there was no accompanying decrease in their aggressive behavior. The theoretical and clinical implications of these findings are discussed.


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