Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity

Acknowledgements This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01- 0145-FEDER-000013), the Fundação para a Ciência e Tecnologia (FCT) (SFRH/BD/136814/2018 to S.M.G., SFRH/BD/141127/2018 to C.D.O., PD/BD/137680/2018 to D.A., IF/00474/2014 to N.S.O., IF/01390/2014 to E.T., IF/00959/2014 to S.C., IF/00021/2014 to R.S., PTDC/SAU-SER/29635/2017 and CEECIND/04601/2017 to C.C., and CEECIND/03628/2017 to A.C.), the Institut Mérieux (Mérieux Research Grant 2017 to C.C.), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Research Grant 2017 to A.C.). M.G.N. was supported by a Spinoza grant of the Netherlands Organization for Scientific Research. A.A.B. was supported by the Deutsche Forschungsgemeinschaft Collaborative Research Center/Transregio TR124 FungiNet (project A1). G.D.B. was funded by the Wellcome Trust (102705), the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPublisher PD

Violacein-Induced Chaperone System Collapse Underlies Multistage Antiplasmodial Activity

Antimalarial drugs with novel modes of action and wide therapeutic potential are needed to pave the way for malaria eradication. Violacein is a natural compound known for its biological activity against cancer cells and several pathogens, including the malaria parasite, Plasmodium falciparum (Pf). Herein, using chemical genomic profiling (CGP), we found that violacein affects protein homeostasis. Mechanistically, violacein binds Pf chaperones, PfHsp90 and PfHsp70-1, compromising the latter's ATPase and chaperone activities. Additionally, violacein-treated parasites exhibited increased protein unfolding and proteasomal degradation. The uncoupling of the parasite stress response reflects the multistage growth inhibitory effect promoted by violacein. Despite evidence of proteotoxic stress, violacein did not inhibit global protein synthesis via UPR activation - a process that is highly dependent on chaperones, in agreement with the notion of a violacein-induced proteostasis collapse. Our data highlight the importance of a functioning chaperone-proteasome system for parasite development and differentiation. Thus, a violacein-like small molecule might provide a good scaffold for development of a novel probe for examining the molecular chaperone network and/or antiplasmodial drug design.publishersversionpublishe

Systematic review of soil ecosystem services in tropical regions

Soil ecosystem service (SES) approaches evidence the importance of soil for human well-being, contribute to improving dialogue between science and decision-making and encourage the translation of scientific results into public policies. Herein, through systematic review, we assess the state of the art of SES approaches in tropical regions. Through this review, 41 publications were identified; while most of these studies considered SES, a lack of a consistent framework to define SES was apparent. Most studies measured soil natural capital and processes, while only three studies undertook monetary valuation. Although the number of publications increased (from 1 to 41), between 2001 and 2019, the total number of publications for tropical regions is still small. Countries with the largest number of publications were Brazil (n = 8), Colombia (n = 6) and Mexico (n = 4). This observation emphasizes an important knowledge gap pertaining to SES approaches and their link to tropical regions. With global momentum behind SES approaches, there is an opportunity to integrate SES approaches into policy and practice in tropical regions. The use of SES evaluation tools in tropical regions could transform how land use decisions are informed, mitigating soil degradation and protecting the ecosystems that soil underpins

Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox

Aim. In recent years, connectivity studies using neuroimaging data have increased the understanding of the organization of large-scale structural and functional brain networks. However, data analysis is time consuming as rigorous procedures must be assured, from structuring data and pre-processing to modality specific data procedures. Until now, no single toolbox was able to perform such investigations on truly multimodal image data from beginning to end, including the combination of different connectivity analyses. Thus, we have developed the Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox with the goal of diminishing time waste in data processing and to allow an innovative and comprehensive approach to brain connectivity.Materials and Methods. The MIBCA toolbox is a fully automated all-in-one connectivity toolbox that offers pre-processing, connectivity and graph theoretical analyses of multimodal image data such as diffusion-weighted imaging, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). It was developed in MATLAB environment and pipelines well-known neuroimaging softwares such as Freesurfer, SPM, FSL, and Diffusion Toolkit. It further implements routines for the construction of structural, functional and effective or combined connectivity matrices, as well as, routines for the extraction and calculation of imaging and graph-theory metrics, the latter using also functions from the Brain Connectivity Toolbox. Finally, the toolbox performs group statistical analysis and enables data visualization in the form of matrices, 3D brain graphs and connectograms. In this paper the MIBCA toolbox is presented by illustrating its capabilities using multimodal image data from a group of 35 healthy subjects (19–73 years old) with volumetric T1-weighted, diffusion tensor imaging, and resting state fMRI data, and 10 subjets with 18F-Altanserin PET data also.Results. It was observed both a high inter-hemispheric symmetry and an intra-hemispheric modularity associated with structural data, whilst functional data presented lower inter-hemispheric symmetry and a high inter-hemispheric modularity. Furthermore, when testing for differences between two subgroups (<40 and >40 years old adults) we observed a significant reduction in the volume and thickness, and an increase in the mean diffusivity of most of the subcortical/cortical regions.Conclusion. While bridging the gap between the high numbers of packages and tools widely available for the neuroimaging community in one toolbox, MIBCA also offers different possibilities for combining, analysing and visualising data in novel ways, enabling a better understanding of the human brain

A diagnosis approach for semiconductor properties evaluation from ab initio calculations: Ag-based materials investigation

Ag-based semiconductors have been extensively employed as photocatalysts for several decades due to their excellent electronic properties, photochemical properties, and relatively low synthesis cost. In this work, the α-Ag2WO4, β-Ag2WO4, γ-Ag2WO4, α-AgVO3, β-AgVO3, α-Ag2MoO4, β-Ag2MoO4, Ag2CrO4, and Ag3PO4 materials were systematically investigated by DFT/B3LYP calculations. The structural features were described by cations coordination, cluster distortion degree, and structure formers and modifiers. In turn, the evaluation of electronic properties indicates band gap values in the range of 2.54 ​eV–4.32 ​eV. The calculated density of charge carriers shows that the holes are the predominant charge carrier for all evaluated semiconductors, except for α-Ag2MoO4. The effective masses of charge carriers were also computed, and good stability for generated electrons and holes are expected for α- and β-Ag2WO4, α-AgVO3, β-AgVO3, β-Ag2MoO4, Ag2CrO4, and Ag3PO4 materials. Finally, the valence and conduction band edge potentials point to the Ag-based semiconductors as promising candidates for photocatalytic and biocide activities

Unraveling the relationship between exposed surfaces and the photocatalytic activity of Ag3PO4: an in-depth theoretical investigation

Over the years, the possibility of using solar radiation in photocatalysis or photodegradation processes hasattracted remarkable interest from scientists around the world. In such processes, due to its electronicproperties, Ag3PO4is one of the most important semiconductors. This work delves into thephotocatalytic activity, stability, and reactivity of Ag3PO4surfaces by comparing plane waves withprojector augmented wave and localized Gaussian basis set simulations, at the atomic level. The resultsindicate that the (110) surface, in agreement with previous experimental reports, displays the mostsuitable characteristics for photocatalytic activity due to its high reactivity,i.e.the presence of a largeamount of undercoordinated Ag cations and a high value work function. Beyond the innovative results,this work shows a good synergy between both kinds of DFT approaches