Chiral evasion and stereospecific antifolate resistance in Staphylococcus aureus

Antimicrobial resistance presents a significant health care crisis. The mutation F98Y in Staphylococcus aureus dihydrofolate reductase (SaDHFR) confers resistance to the clinically important antifolate trimethoprim (TMP). Propargyl-linked antifolates (PLAs), next generation DHFR inhibitors, are much more resilient than TMP against this F98Y variant, yet this F98Y substitution still reduces efficacy of these agents. Surprisingly, differences in the enantiomeric configuration at the stereogenic center of PLAs influence the isomeric state of the NADPH cofactor. To understand the molecular basis of F98Y-mediated resistance and how PLAs’ inhibition drives NADPH isomeric states, we used protein design algorithms in the osprey protein design software suite to analyze a comprehensive suite of structural, biophysical, biochemical, and computational data. Here, we present a model showing how F98Y SaDHFR exploits a different anomeric configuration of NADPH to evade certain PLAs’ inhibition, while other PLAs remain unaffected by this resistance mechanism.     

Controls for Phylogeny and Robust Analysis in Pareto Task Inference

Understanding the tradeoffs faced by organisms is a major goal of evolutionary biology. One of the main approaches for identifying these tradeoffs is Pareto task inference (ParTI). Two recent papers claim that results obtained in ParTI studies are spurious due to phylogenetic dependence (Mikami T, Iwasaki W. 2021. The flipping t-ratio test: phylogenetically informed assessment of the Pareto theory for phenotypic evolution. Methods Ecol Evol. 12(4):696–706) or hypothetical p-hacking and population-structure concerns (Sun M, Zhang J. 2021. Rampant false detection of adaptive phenotypic optimization by ParTI-based Pareto front inference. Mol Biol Evol. 38(4):1653–1664). Here, we show that these claims are baseless. We present a new method to control for phylogenetic dependence, called SibSwap, and show that published ParTI inference is robust to phylogenetic dependence. We show how researchers avoided p-hacking by testing for the robustness of preprocessing choices. We also provide new methods to control for population structure and detail the experimental tests of ParTI in systems ranging from ammonites to cancer gene expression. The methods presented here may help to improve future ParTI studies.     

The ecology of the banded civet (Hemigalus derbyanus) in Southeast Asia with implications for mesopredator release,zoonotic diseases,and conservation

Habitat loss and degradation threaten forest specialist wildlife species, but some generalist mesopredators exploit disturbed areas and human‐derived food, which brings them into closer contact with humans. Mesopredator release is also important for human health for known zoonotic disease reservoirs, such as Asian civets (Viverridae family), since this group includes the intermediator species for the SARS‐CoV‐1 outbreak. Here we use camera trapping to evaluate the habitat associations of the widespread banded civet (Hemigalus derbyanus) across its range in Southeast Asia. At the regional scale, banded civet detections among published studies were positively associated with forest cover and negatively associated with human population. At the local scale (within a landscape), hierarchical modeling of new camera trapping showed that abundance was negatively associated with forest loss and positively associated with distance to rivers. These results do not support mesopredator release and suggest a low likelihood overlap with humans in degraded habitats and, therefore, a low risk of zoonotic disease transmission from this species in the wild. We also estimate that banded civet distribution has contracted to under 21% of its currently recognized IUCN Red List range, only 12% of which falls within protected areas, and a precipitous recent decline in population size. Accordingly, we suggest the banded civet''s Red List status should be re‐evaluated in light of our findings.     

Spatial dynamics of Chinese Muntjac related to past and future climate fluctuations

Climate fluctuations in the past and in the future are likely to result in population expansions,shifts,or the contraction of the ecological niche of many speci...     

Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen

Discoidin domain receptor 2 (DDR2) is an unusual receptor tyrosine kinase in that its ligand is fibrillar collagen rather than a growth factor-like peptide. We examined signal transduction pathways of DDR2. Here we show that DDR2 is also unusual in that it requires Src activity to be maximally tyrosine-phosphorylated, and that Src activity also promotes association of DDR2 with Shc. The interaction with Shc involves a portion of Shc not previously implicated in interaction with receptor tyrosine kinases. These results identify Src kinase and the adaptor protein Shc as key signaling intermediates in DDR2 signal transduction. Furthermore, Src is required for DDR2-mediated transactivation of the matrix metalloproteinase-2 promoter. The data support a model in which Src and the DDR2 receptor cooperate in a regulated fashion to direct the phosphorylation of both the receptor and its targets.     

Changing Paradigms in Seagrass Restoration

Sharing experiences and results among scientists and managers working on seagrass restoration was the main objective of the first European Seagrass Restoration Workshop that gathered researchers from around Europe. The meeting was the first forum in Europe that allowed for scientists, NGOs, and managers to interact and share their experiences relating to seagrass restoration and management. The results show that none of the seagrass restoration programs developed in Europe by the participants during the last 10 years was successful. Furthermore, an informal review of data published in seagrass restoration success, showed that the results reported were biased because they were mostly based on a very short monitoring period (i.e. < 1 year). Numerous decision trees, guidelines, and restoration models have been developed to aid seagrass restoration management, but the results of this workshop point toward a new paradigm in seagrass restoration were efforts should shift to give priority to natural restoration potential, with an emphasis on the fact that restoration should never be considered the first alternative when planning for the mitigation of coastal development projects or to justify mitigation as a compensation measure for economic activities.     

Non-Hebbian Learning Implementation in Light-Controlled Resistive Memory Devices

Non-Hebbian learning is often encountered in different bio-organisms. In these processes, the strength of a synapse connecting two neurons is controlled not only by the signals exchanged between the neurons, but also by an additional factor external to the synaptic structure. Here we show the implementation of non-Hebbian learning in a single solid-state resistive memory device. The output of our device is controlled not only by the applied voltages, but also by the illumination conditions under which it operates. We demonstrate that our metal/oxide/semiconductor device learns more efficiently at higher applied voltages but also when light, an external parameter, is present during the information writing steps. Conversely, memory erasing is more efficiently at higher applied voltages and in the dark. Translating neuronal activity into simple solid-state devices could provide a deeper understanding of complex brain processes and give insight into non-binary computing possibilities.