Modeling Coupled Disease-Behavior Dynamics of SARS-CoV-2 Using Influence Networks

SARS-CoV-2, the virus that causes COVID-19, has caused significant human morbidity and mortality since its emergence in late 2019. Not only have over three million people died, but humans have been forced to change their behavior in a variety of ways, including limiting their contacts, social distancing, and wearing masks. Early infectious disease models, like the classical SIR model by Kermack and McKendrick, do not account for differing contact structures and behavior. More recent work has demonstrated that contact structures and behavior can considerably impact disease dynamics. We construct a coupled disease-behavior dynamical model for SARS-CoV-2 by incorporating heterogeneous contact structures and decisions about masking. We use a contact network with household, work, and friend interactions to capture the variation in contact patterns. We allow decisions about masking to occur at a different time scale from disease spread which dramatically changes the masking dynamics. Drawing from the field of game theory, we construct an individual decision-making process that relies on perceived risk of infection, social influence, and individual resistance to masking. Through simulation, we find that social influence prevents masking, while perceived risk largely drives individuals to mask. Underlying contact structure also affects the number of people who mask. This model serves as a starting point for future work which could explore the relative importance of social influence and perceived risk in human decision-making

Evaluating the Economic and Environmental Sustainability of Integrated Farming Systems

Economic and environmental sustainability has become a major concern for forage-based animal production in Europe, North America and other parts of the world. Development of more sustainable farming systems requires an assimilation of experimental and modelling research. Field research is critical for supporting the development and evaluation of models, and modelling is needed to integrate farm components for predicting the long-term effects and interactions resulting from farm management changes. Experimentally supported simulation provides a tool for evaluating and comparing farming strategies and predicting their effect on the watershed, region and beyond

Structural Features of Condensed Tannins Influence Their Antimethanogenic Potential in Forage Plants

Despite years of research on the antimethanogenic potential of condensed tannins (CT), their large-scale application is inhibited by a substantial variability in previous studies with regards to their impact on ruminant nutrition. This variability mainly results from the complexity of CT structures, and their impact on methane emissions is often unaccounted for. Hence, this study (a) evaluated the variability in antimethanogenic potential across six forage species, (b) linked methane emissions to tannin activity, and (c) determined the impact of CT structural features on methane abatement. Six forage species were grown in a greenhouse under controlled environmental conditions, namely, sainfoin (Onobrychis viciifolia), birdsfoot trefoil (Lotus corniculatus), big trefoil (Lotus pedunculatus), plantain (Plantaga lanceolata), sulla (Hedysarum coronarium) and lucerne (Medicago sativa). The plants were harvested at the flowering stage and leaf samples were analysed for chemical composition, condensed tannin concentration and structural features, before being incubated in rumen fluid for 24 hours. Lucerne was used as negative control (without tannins) and an additional polyethylene glycol (PEG) treatment was included, to inactivate tannins and link any effect on fermentation characteristics to tannin activity only. A strong variability across the species (P\u3c 0.0001) was observed on methane emissions. Sulla had the highest antimethanogenic potential and decreased methane emissions by 47% compared to lucerne. All species rich in CTs decreased both methane and total gas production, yet the PEG treatment did not alter the methane proportion in the total gas produced. In addition to CT concentration (R= -0.78), methane emissions were found to be negatively correlated with the CT structural features, prodelphinidin percentage (R= -0.6) and mean degree of polymerisation (R= -0.57). This study demonstrated that antimethanogenic potential of forages depends on CT concentration as well as on structural features and incorporating them in the studies can efficiently assess their impact on ruminant nutrition

Assessing the Potential of Diverse Forage Mixtures to Reduce Enteric CH\u3csub\u3e4\u3c/sub\u3e Emissions

Enteric methane (CH4) is a main source of agriculture-related greenhouse gasses. Conversely, pasture is increasingly demanded by customers due to both perceived and real benefits regarding animal welfare, environmental aspects and product quality. However, if implemented poorly, CH4 emissions can increase, thus contributing to climate change. One promising option to reduce enteric CH4 emissions are plant specialized metabolites (PSM), and particularly tannins. Consequently, we conducted two complementary experiments to determine to what extent enteric CH4 emissions can be reduced, and how this affects milk yields: a) an in vivo experiment with grazing Jersey cows, where CH4 emissions were quantified using the SF6 tracer technique, and b) an in vitro experiment using the Hohenheim gas test. In the in vivo experiment, a binary mixture consisting of perennial ryegrass (Lolium perenne) and white clover (Trifolium repens) was compared against a diverse mixture consisting of eight species, including birdsfoot trefoil (Lotus corniculatus), and salad burnet (Sanguisorba minor). In the in vitro experiment, the eight species from the in vivo experiment were combined in binary mixtures with perennial ryegrass in increasing proportions, to determine the mitigation potential of each species. Results show an increase in milk yield for the diverse mixture, although this is also accompanied by higher CH4 emissions. Nevertheless, these emissions are lower across both mixtures, when compared with similar trials. This is probably due to a very high digestibility of the ingested forage. With the in vitro experiment, we were able to confirm a substantial potential for CH4 reduction when including species rich in PSM. However, those forbs with the higher anti-methanogenic potential were only present in minor proportions in the pasture. Hence, further research will be required on how to increase the share of the bioactive species with lower competitiveness and confirm their potential in vivo

The T210M Substitution in the HLA-a*02:01 gp100 Epitope Strongly Affects Overall Proteasomal Cleavage Site Usage and Antigen Processing

MHC class I-restricted epitopes, which carry a tumor-specific mutation resulting in improved MHC binding affinity, are preferred T cell receptor targets in innovative adoptive T cell therapies. However, T cell therapy requires efficient generation of the selected epitope. How such mutations may affect proteasome-mediated antigen processing has so far not been studied. Therefore, we analyzed by in vitro experiments the effect on antigen processing and recognition of a T210M exchange, which previously had been introduced into the melanoma gp100209–217tumor epitope to improve the HLA-A*02:01 binding and its immunogenicity. A quantitative analysis of the main steps of antigen processing shows that the T210M exchange affects proteasomal cleavage site usage within the mutgp100201–230 polypeptide, leading to the generation of an unique set of cleavage products. The T210M substitution qualitatively affects the proteasome-catalyzed generation of spliced and non-spliced peptides predicted to bind HLA-A or -B complexes. The T210M substitution also induces an enhanced production of the mutgp100209–217 epitope and its N-terminally extended peptides. The T210M exchange revealed no effect on ERAP1-mediated N-terminal trimming of the precursor peptides. However, mutant N-terminally extended peptides exhibited significantly increased HLA-A*02:01 binding affinity and elicited CD8+ T cell stimulation in vitro similar to the wtgp100209–217 epitope. Thus, our experiments demonstrate that amino acid exchanges within an epitope can result in the generation of an altered peptide pool with new antigenic peptides and in a wider CD8+ T cell response also towards N-terminally extended versions of the minimal epitope

Fused in sarcoma silences HIV gene transcription and maintains viral latency through suppressing AFF4 gene activation

Background: The human immunodeficiency virus (HIV) cell reservoir is currently a main obstacle towards complete eradication of the virus. This infected pool is refractory to anti-viral therapy and harbors integrated proviruses that are transcriptionally repressed but replication competent. As transcription silencing is key for establishing the HIV reservoir, significant efforts have been made to understand the mechanism that regulate HIV gene transcription, and the role of the elongation machinery in promoting this step. However, while the role of the super elongation complex (SEC) in enhancing transcription activation of HIV is well established, the function of SEC in modulating viral latency is less defined and its cell partners are yet to be identified. Results: In this study we identify fused in sarcoma (FUS) as a partner of AFF4 in cells. FUS inhibits the activation of HIV transcription by AFF4 and ELL2, and silences overall HIV gene transcription. Concordantly, depletion of FUS elevates the occupancy of AFF4 and Cdk9 on the viral promoter and activates HIV gene transcription. Live cell imaging demonstrates that FUS co-localizes with AFF4 within nuclear punctuated condensates, which are disrupted upon treating cells with aliphatic alcohol. In HIV infected cells, knockout of FUS delays the gradual entry of HIV into latency, and similarly promotes viral activation in a T cell latency model that is treated with JQ1. Finally, effects of FUS on HIV gene transcription are also exhibited genome wide, where FUS mainly occupies gene promoters at transcription starting sites, while its knockdown leads to an increase in AFF4 and Cdk9 occupancy on gene promoters of FUS affected genes. Conclusions: Towards eliminating the HIV infected reservoir, understanding the mechanisms by which the virus persists in the face of therapy is important. Our observations show that FUS regulates both HIV and global gene transcription and modulates viral latency, thus can potentially serve as a target for future therapy that sets to reactivate HIV from its latent state.Israel Science Foundation [755/17]; Ben-Gurion University of the Negev, Israel; National Institute of Health [NS082376]; Office of the Director of the NIH [S10OD013237]; NIH [R21AI127274]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The non-coding rna journal club: Highlights on recent papers-8

We are glad to share with you our eighth Journal Club and to highlight some of the most interesting papers published recently [...