Predicting Bevirimat resistance of HIV-1 from genotype

<p>Abstract</p> <p>Background</p> <p>Maturation inhibitors are a new class of antiretroviral drugs. Bevirimat (BVM) was the first substance in this class of inhibitors entering clinical trials. While the inhibitory function of BVM is well established, the molecular mechanisms of action and resistance are not well understood. It is known that mutations in the regions CS p24/p2 and p2 can cause phenotypic resistance to BVM. We have investigated a set of p24/p2 sequences of HIV-1 of known phenotypic resistance to BVM to test whether BVM resistance can be predicted from sequence, and to identify possible molecular mechanisms of BVM resistance in HIV-1.</p> <p>Results</p> <p>We used artificial neural networks and random forests with different descriptors for the prediction of BVM resistance. Random forests with hydrophobicity as descriptor performed best and classified the sequences with an area under the Receiver Operating Characteristics (ROC) curve of 0.93 ± 0.001. For the collected data we find that p2 sequence positions 369 to 376 have the highest impact on resistance, with positions 370 and 372 being particularly important. These findings are in partial agreement with other recent studies. Apart from the complex machine learning models we derived a number of simple rules that predict BVM resistance from sequence with surprising accuracy. According to computational predictions based on the data set used, cleavage sites are usually not shifted by resistance mutations. However, we found that resistance mutations could shorten and weaken the <it>α</it>-helix in p2, which hints at a possible resistance mechanism.</p> <p>Conclusions</p> <p>We found that BVM resistance of HIV-1 can be predicted well from the sequence of the p2 peptide, which may prove useful for personalized therapy if maturation inhibitors reach clinical practice. Results of secondary structure analysis are compatible with a possible route to BVM resistance in which mutations weaken a six-helix bundle discovered in recent experiments, and thus ease Gag cleavage by the retroviral protease.</p

SNAPSHOT USA 2019 : a coordinated national camera trap survey of the United States

This article is protected by copyright. All rights reserved.With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August - 24 November of 2019). We sampled wildlife at 1509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the USA. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as well as future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.Publisher PDFPeer reviewe

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Characterization of the small flavin-binding dodecin in the roseoflavin producer Streptomyces davawensis

Ludwig P, Sevin DC, Busche T, et al. Characterization of the small flavin-binding dodecin in the roseoflavin producer Streptomyces davawensis. MICROBIOLOGY-SGM. 2018;164(6):908-919.Genes encoding dodecin proteins are present in almost 20% of archaeal and in more than 50% of bacterial genomes. Archaeal dodecins bind riboflavin (vitamin B-2), are thought to play a role in flavin homeostasis and possibly also help to protect cells from radical or oxygenic stress. Bacterial dodecins were found to bind riboflavin-5'-phosphate (also called flavin mononucleotide or FMN) and coenzyme A, but their physiological function remained unknown. In this study, we set out to investigate the relevance of dodecins for flavin metabolism and oxidative stress management in the phylogenetically related bacteria Streptomyces coelicolor and Streptomyces davawensis. Additionally, we explored the role of dodecins with regard to resistance against the antibiotic roseoflavin, a riboflavin analogue produced by S. davawensis. Our results show that the dodecin of S. davawensis predominantly binds FMN and is neither involved in roseoflavin biosynthesis nor in roseoflavin resistance. In contrast to S. davawensis, growth of S. coelicolor was not reduced in the presence of plumbagin, a compound, which induces oxidative stress. Plumbagin treatment stimulated expression of the dodecin gene in S. davawensis but not in S. coelicolor. Deletion of the dodecin gene in S. davawensis generated a recombinant strain which, in contrast to the wild-type, was fully resistant to plumbagin. Subsequent metabolome analyses revealed that the S. davawensis dodecin deletion strain exhibited a very different stress response when compared to the wild-type indicating that dodecins broadly affect cellular physiology

Anthropologie de l’immigration

L'immigration donne lieu à de nombreux débats d'où l'anthropologie est assez souvent absente. Cela tient sans doute à ce que d'autres disciplines occupent le devant de la scène. En même temps, l'étude des phénomènes migratoires privilégie les ressortissants du Maghreb. Ce cahier présente un point de vue anthropologique sur l'immigration où les populations originaires des pays du Maghreb aussi bien que d'Italie ou de l'Europe de l'Est (les Tziganes) sont prises en considération dans une perspective comparatiste. Une partie des contributions est consacrée à l'anthropologie culturelle et critique les conceptions qui enferment les migrants dans une sorte d'«identité culturelle». D'autres points de vue sont, toutefois, représentés. Une seconde partie est consacrée à l'anthropologie biologique et, plus particulièrement, à ses apports spécifiques : l'étude des comportements féconds, des pratiques alimentaires et des généalogies. Ce cahier réunit des contributions qui matérialisent une coopération entre plusieurs universités et centres de recherche européens

Consistency across multi-omics layers in a drug-perturbed gut microbial community

Pre-processed data used for generating figures of the paper. </p

Bioaccumulation of therapeutic drugs by human gut bacteria

Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping ofthe interactions between drugs and bacteria has only started recently' and the main underlying mechanism proposed is the chemical transformation of drugs by microorganisms (biotransformation). Here we investigated the depletion of 15 structurally diverse drugs by 25 representative strains of gut bacteria. This revealed 70 bacteria-drug interactions, 29 of which had not to our knowledge been reported before. Over half of the new interactions can be ascribed to bioaccumulation; that is, bacteria storing the drug intracellularly without chemically modifying it, and in most cases without the growth ofthe bacteria being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click chemistry, thermal proteome profiling and metabolomics. We find that duloxetine bindsto several metabolic enzymes and changes the metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the composition of the community through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioural response of Caenorhabditis elegansto duloxetine. Together, our results show that bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, probably in an individual manner