A virtual pebble game to ensemble average graph rigidity

Previous works have demonstrated that protein rigidity is related to thermodynamic stability, especially under conditions that favor formation of native structure. Mechanical network rigidity properties of a single conformation are efficiently calculated using the in- teger Pebble Game (PG) algorithm. However, thermodynamic properties require averaging over many samples from the ensemble of accessible conformations, leading to fluctuations within the network. We have developed a mean field Virtual Pebble Game (VPG) that provides a probabilistic description of the interaction network, meaning that sampling is not required. We extensively test the VPG algorithm over a variety of body-bar networks created on disordered lattices, from these calculations we fully characterize the network conditions under which the performance of the VPG offers the best solution. The VPG provides a satisfactory description of the ensemble averaged PG properties, especially in regions removed from the rigidity transition where ensemble fluctuations are greatest. In further experiments, we characterized the VPG across a structurally nonredundant dataset of 272 proteins. Using quantitative and visual assessments of the rigidity characterizations, the VPG results are shown to accurately reflect the ensemble averaged PG properties. That is, the fluctuating interaction network is well represented by a single calculation that re- places density functions with average values, thus speeding up the desired calculation by several orders of magnitude. Finally, we propose a new algorithm that is based on the combination of PG and VPG to balance the amount of sampling and mean field treatment. While offering interesting results, this approach needs to be further optimized to fully lever- age its utility. All these results positions the VPG as an efficient alternative to understand the mechanical role that chemical interactions play in maintaining protein stability

Reinforcement of Polymeric Nanoassemblies for Ultra-High Drug Loadings, Modulation of Stiffness and Release Kinetics, and Sustained Therapeutic Efficacy

The optimization of current polymeric nanoparticle therapies is restricted by low drug loadings and limited tunability of core properties. To overcome these shortcomings, a novel self-association approach is utilized to fabricate a dual-loaded poly(1,2-glycerol carbonate)-graft-succinic acid-paclitaxel (PGC-PTX) conjugate nanoparticle (NP) in which the physical entrapment of free paclitaxel (PTX) affords unprecedented ultra-high drug loadings >100 wt%, modulation of mechanical stiffness, and tunable release kinetics. Despite high incorporation of free PTX (up to 50 wt%), the dual-loaded PGC-PTX nanocarriers (i.e., PGC-PTX + PTX NPs) exhibit controlled and sustained drug release over 15 days, without burst release effects. Importantly, optimization of drug/material efficiency concomitantly affords improved in vitro efficacy. In vivo, PGC-PTX + PTX NPs are safely administered at doses exceeding the median lethal dose of standard PTX, while a single high dose significantly extends survival relative to weekly PTX administrations in a murine model of peritoneal carcinomatosis

Network Analysis of Host-Virus Communities in Bats and Rodents Reveals Determinants of Cross-Species Transmission

Bats are natural reservoirs of several important emerging viruses. Cross-species transmission appears to be quite common among bats, which may contribute to their unique reservoir potential. Therefore, understanding the importance of bats as reservoirs requires examining them in a community context rather than concentrating on individual species. Here, we use a network approach to identify ecological and biological correlates of cross-species virus transmission in bats and rodents, another important host group. We show that given our current knowledge the bat viral sharing network is more connected than the rodent network, suggesting viruses may pass more easily between bat species. We identify host traits associated with important reservoir species: gregarious bats are more likely to share more viruses and bats which migrate regionally are important for spreading viruses through the network. We identify multiple communities of viral sharing within bats and rodents and highlight potential species traits that can help guide studies of novel pathogen emergence

Flerovium spectroscopy – benchmarking nuclear theory at proton number Z = 114

In the wake of the discovery of superheavy elements, nuclear spectroscopy experiments aim at providing anchor points at the uppermost end of the nuclear chart for nuclear structure theory, which otherwise had to solely rely on extrapolations. In two runs in 2019 and 2020, such a nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z = 114). One incentive to study flerovium isotopes is that many, but not all, nuclear structure models or model parametrizations favour Z = 114 as the next magic proton number beyond lead, Z = 82

Identification of commensal bacteria autoinducing peptides with ultrahigh performance liquid chromatography - high resolution mass spectrometry

Staphylococcus aureus is an opportunistic pathogen that has become an increasing issue over the years due to its acquired resistance to different antibiotics such as methicillin. The development of resistance has sparked interest in finding new ways to combat S. aureus, and other pathogens. Recent hypotheses suggest that different types of commensal bacteria in the skin are able to cross-inhibit virulence in S. aureus, by suppressing the production of its virulence factors responsible for disease. Cross-inhibition is believed to involve autoinducing signaling molecules that are unique to different bacterial species. These signaling molecules are responsible for self-regulating functions in a bacterium that produces them and for potentially disrupting similar processes in other species. More knowledge is needed about how these signaling molecules from commensal bacteria can affect quorum sensing in the bacterial pathogen S. aureus, however, in order to further study these interactions, the properties of the signaling molecules must be known, starting with their molecular structure. The goal of this project is to detect and elucidate the structures of unknown signaling molecules from different commensal staphylococcal species that have previously displayed cross-inhibition activity against quorum sensing in S. aureus

Chytrids Vs. Amphibians: Emerging Disease Or History Of Natural Selection?

Quantity of skin peptides and effectiveness of those peptides in suppressing the growth of Batrachochytrium dendrobatidis were analyzed for 134 individuals of 24 species of amphibians from the Southern Appalachian temperate zone of eastern North America and several Costa Rica sites in the tropics

Ecological approaches in veterinary epidemiology: mapping the risk of bat-borne rabies using vegetation indices and night-time light satellite imagery

Rabies remains a disease of significant public health concern. In the Americas, bats are an important source of rabies for pets, livestock, and humans. For effective rabies control and prevention, identifying potential areas for disease occurrence is critical to guide future research, inform public health policies, and design interventions. To anticipate zoonotic infectious diseases distribution at coarse scale, veterinary epidemiology needs to advance via exploring current geographic ecology tools and data using a biological approach. We analyzed bat-borne rabies reports in Chile from 2002 to 2012 to establish associations between rabies occurrence and environmental factors to generate an ecological niche model (ENM). The main rabies reservoir in Chile is the bat species Tadarida brasiliensis; we mapped 726 occurrences of rabies virus variant AgV4 in this bat species and integrated them with contemporary Normalized Difference Vegetation Index (NDVI) data from the Moderate Resolution Imaging Spectroradiometer (MODIS). The correct prediction of areas with rabies in bats and the reliable anticipation of human rabies in our study illustrate the usefulness of ENM for mapping rabies and other zoonotic pathogens. Additionally, we highlight critical issues with selection of environmental variables, methods for model validation, and consideration of sampling bias. Indeed, models with weak or incorrect validation approaches should be interpreted with caution. In conclusion, ecological niche modeling applications for mapping disease risk at coarse geographic scales have a promising future, especially with refinement and enrichment of models with additional information, such as night-time light data, which increased substantially the model’s ability to anticipate human rabies

Characterization of a multi-tolerant tannin acyl hydrolase II from Aspergillus carbonarius produced under solid-state fermentation

Background: Tannases are enzymes with biotechnological potential produced mainly by microorganisms as filamentous fungi. In this context, the production and characterization of a multi-tolerant tannase from Aspergillus carbonarius is described. Results: The filamentous fungus A. carbonarius produced high levels of tannasewhen cultivated under solid-state fermentation using green tea leaves as substrate/carbon source and tapwater at a 1:1 ratio as the moisture agent for 72 h at 30\ub0C. Two tannase activity peakswere obtained during the purification step usingDEAE-Cellulose. The second peak (peak II) was purified 11-fold with 14% recovery from a Sepharose CL-6B chromatographic column. The tannase frompeak II (tannase II)was characterized as a heterodimeric glycoprotein of 134.89 kDa, estimated through gel filtration,with subunits of 65 kDa and 100 kDa, estimated through SDS-PAGE, and 48% carbohydrate content. The optimal temperature and pH for tannase II activity was 60\ub0C and 5.0, respectively. The enzyme was fully stable at temperatures ranging from 20\u201360\ub0C for 120 min, and the half-life (T1/2) at 75\ub0C was 62 min. The activation energy was 28.93 kJ/mol. After incubation at pH 5.0 for 60 min, 75% of the enzyme activity was maintained. However, enzyme activity was increased in the presence of AgNO3 and it was tolerant to solvents and detergents. Tannase II exhibited a better affinity for methyl gallate (Km = 1.42 mM) rather than for tannic acid (Km = 2.2 mM). Conclusion: A. carbonarius tannase presented interesting properties as, for example, multi-tolerance, which highlight its potential for future application

Rolling resistance contribution to a road pavement life cycle carbon footprint analysis

Purpose Although the impact of road pavement surface condition on rolling resistance has been included in the life cycle assessment (LCA) framework of several studies in the last years, there is still a high level of uncertainty concerning the methodological assumptions and the parameters that can affect the results. In order to adopt pavement carbon footprint/LCA as a decision-making tool, it is necessary to explore the impact of the chosen methods and assumptions on the LCA results. Methods This paper provides a review of the main models describing the impact of the pavement surface properties on vehicle fuel consumption and analyses the influence of the methodological assumptions related to the rolling resistance on the LCA results. It compares the CO2 emissions, calculated with two different rolling resistance models existing in literature, and performs a sensitivity test on some specific input variables (pavement deterioration rate, traffic growth, and emission factors/fuel efficiency improvement). Results and discussion The model used to calculate the impact of the pavement surface condition on fuel consumption significantly affects the LCA results. The pavement deterioration rate influences the calculation in both models, while traffic growth and fuel efficiency improvement have a limited impact on the vehicle CO2 emissions resulting from the pavement condition contribution to rolling resistance. Conclusions and recommendations Existing models linking pavement condition to rolling resistance and hence vehicle emissions are not broadly applicable to the use phase of road pavement LCA and further research is necessary before a widely-used methodology can be defined. The methods of modelling and the methodological assumptions need to be transparent in the analysis of the impact of the pavement surface condition on fuel consumption, in order to be interpreted by decision makers and implemented in an LCA framework. This will be necessary before product category rules (PCR) for pavement LCA can be extended to include the use phase