Search bioRxiv⌕ Search

Biology subjects

Krug, R. M.

Publications and source records attributed to Krug, R. M..

4 recordsLinked to original sources

Biodiversity increases the forecastability of species abundances in changing environments

Accurate forecasts of ecological dynamics are critical for ecosystem management and conservation, yet the drivers of forecastability are poorly understood. Environmental change and diversity are considered major challenges to ecological forecasting. This assumption, however, has never been tested experimentally because forecasts have high data requirements. In a long-term microcosm experiment, we manipulated species richness of 30 experimental protist communities and exposed them to constant or gradually decreasing light levels. We collected finely-resolved time series (123 sampling dates over 41 weeks) of species abundances, community biomass, and oxygen concentrations. We then employed data-driven forecasting methods to forecast these variables. We found that species richness and light had a weak interactive effect on forecasts of species abundances: richness tended to reduce forecast accuracy in constant light but tended to increase forecast accuracy in declining light. These effects could partially be explained by differences among time series in variability and autocorrelation. Forecasts of aggregate properties (community biomass, oxygen), however, were unaffected by richness and light, and were not more accurate than those of species abundances. Our forecasts were based on time series that were detrended and standardized. Since real-world forecasting applications require predictions at the original scale of the forecasted variable, it is important to note that the results were qualitatively identical when back-transforming the forecasts to the original scale. Taken together, we found no strong evidence that higher diversity results in lower forecastability. Rather, our results imply that promoting diversity could make populations more predictable when environmental conditions change. From a conservation and management perspective, our findings suggest that diversity conservation might have beneficial effects on decision-taking by increasing the forecastability of species abundances in changing environments.

ecology↗

The NS1 protein of influenza B virus binds 5'-triphosphorylated dsRNA to suppress RIG-I activation and the antiviral innate immune response

Influenza A and B viruses overcome the host antiviral response to cause a contagious and often severe human respiratory disease. Here, integrative structural biology and biochemistry studies on non- structural protein 1 of influenza B virus (NS1B) reveal a previously unrecognized viral mechanism for innate immune evasion. Conserved basic groups of its C-terminal domain (NS1B-CTD) bind 5- triphosphorylated double-stranded RNA (5ppp-dsRNA), the primary pathogen-associated feature that activates the host retinoic acid-inducible gene I protein (RIG-I) to initiate interferon synthesis and the cellular antiviral response. Like RIG-I, NS1B-CTD preferentially binds blunt-end 5ppp-dsRNA. NS1B-CTD also competes with RIG-I for binding 5ppp-dsRNA, and thus suppresses activation of RIG-Is ATPase activity. Although the NS1B N-terminal domain also binds dsRNA, it utilizes a different binding mode and lacks 5ppp-dsRNA end preferences. In cells infected with wild-type influenza B virus, RIG-I activation is inhibited. In contrast, RIG-I activation and the resulting phosphorylation of transcription factor IRF-3 are not inhibited in cells infected with a mutant virus encoding NS1B with a R208A substitution it its CTD that eliminates its 5ppp-dsRNA binding activity. These results reveal a novel mechanism in which NS1B binds 5ppp-dsRNA to inhibit the RIG-I antiviral response during influenza B virus infection, and open the door to new avenues for antiviral drug discovery.

biochemistry↗

Microxanox: an R package for simulating an aquatic MICRobial ecosystem that can occupy OXic or ANOXic states

Microxanox is an R package to simulate a three functional group ecosystem (cyanobacteria, phototrophic sulfur bacteria, and sulfate-reducing bacteria) with four chemical substrates (phosphorus, oxygen, reduced sulfur, and oxidized sulfur) using a set of ordinary differential equations. Simulations can be run individually or over a parameter range, to find stable states. The model can be implemented with different numbers of species per functional group. The package is constructed in such a way that the results contain the input parameter used, so that a saved results can be loaded again and the simulation be repeated. Furthermore, the package framework and code should serve as a useful starting point for making simulation models of other types of ecosystem.

ecology↗

Hepatitis C Virus Drugs Simeprevir and Grazoprevir Synergize with Remdesivir to Suppress SARS-CoV-2 Replication in Cell Culture

Effective control of COVID-19 requires antivirals directed against SARS-CoV-2 virus. Here we assess ten available HCV protease inhibitor drugs as potential SARS-CoV-2 antivirals. There is a striking structural similarity of the substrate binding clefts of SARS- CoV-2 Mpro and HCV NS3/4A proteases, and virtual docking experiments show that all ten HCV drugs can potentially bind into the Mpro binding cleft. Seven of these HCV drugs inhibit SARS-CoV-2 Mpro protease activity, while four dock well into the PLpro substrate binding cleft and inhibit PLpro protease activity. These same seven HCV drugs inhibit SARS-CoV-2 virus replication in Vero and/or human cells, demonstrating that HCV drugs that inhibit Mpro, or both Mpro and PLpro, suppress virus replication. Two HCV drugs, simeprevir and grazoprevir synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, thereby increasing remdesivir inhibitory activity as much as 10-fold. HighlightsO_LISeveral HCV protease inhibitors are predicted to inhibit SARS-CoV-2 Mpro and PLpro. C_LIO_LISeven HCV drugs inhibit Mpro enzyme activity, four HCV drugs inhibit PLpro. C_LIO_LISeven HCV drugs inhibit SARS-CoV-2 replication in Vero and/or human cells. C_LIO_LIHCV drugs simeprevir and grazoprevir synergize with remdesivir to inhibit SARS- CoV-2. C_LI eTOC blurbBafna, White and colleagues report that several available hepatitis C virus drugs inhibit the SARS-CoV-2 Mpro and/or PLpro proteases and SARS-CoV-2 replication in cell culture. Two drugs, simeprevir and grazoprevir, synergize with the viral polymerase inhibitor remdesivir to inhibit virus replication, increasing remdesivir antiviral activity as much as 10-fold. O_FIG O_LINKSMALLFIG WIDTH=185 HEIGHT=200 SRC="FIGDIR/small/422511v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1c12181org.highwire.dtl.DTLVardef@7ed993org.highwire.dtl.DTLVardef@1fe56aaorg.highwire.dtl.DTLVardef@ebc34e_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗