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11 pags., 5 figs., FF-ATP synthase (ATP synthase) is a central membrane protein that synthetizes most of the ATP in the cell through a rotational movement driven by a proton gradient across the hosting membrane. In mitochondria, ATP synthases can form dimers through specific interactions between some subunits of the protein. The dimeric form of ATP synthase provides the protein with a spontaneous curvature that sustain their arrangement at the rim of the high-curvature edges of mitochondrial membrane (cristae). Also, a direct interaction with cardiolipin, a lipid present in the inner mitochondrial membrane, induces the dimerization of ATP synthase molecules along cristae. The deletion of those biochemical interactions abolishes the protein dimerization producing an altered mitochondrial function and morphology. Mechanically, membrane bending is one of the key deformation modes by which mitochondrial membranes can be shaped. In particular, bending rigidity and spontaneous curvature are important physical factors for membrane remodelling. Here, we discuss a complementary mechanism whereby the rotatory movement of the ATP synthase might modify the mechanical properties of lipid bilayers and contribute to the formation and regulation of the membrane invaginations., I.L.-M. and M.P.L. acknowledge financial support from the Spanish Ministry of Science, Innovation and Universities through the grant PGC2018-097903-B-I00. This work was also supported by the TECNOLOG ́IAS 2018 program funded by the Regional Government of Madrid (Grant S2018/BAA-4403 SINOXPHOS-CM). JL.A acknowledges financial support from the Spanish Ministry of Science, Innovation and Universities through the grant RTI2018-101953-A-100. JL.A also thanks the fellowship from ‘‘la Caixa’’ Foundation (ID 100010434). The fellowship code is LCF/BQ/LI18/11630021. D.V.G thanks the Regional Government of Madrid for an assistant researcher contract (CT103/19/ PEJ-2019-AI/IND-13687).

16 páginas, 10 figuras, 5 tablas, The plant microbiome is likely to play a key role in the resilience of communities to the global climate change. This research analyses the culturable fungal mycobiota of Brachypodium rupestre across a sharp gradient of disturbance caused by an intense, anthropogenic fire regime. This factor has dramatic consequences for the community composition and diversity of high-altitude grasslands in the Pyrenees. Plants were sampled at six sites, and the fungal assemblages of shoots, rhizomes, and roots were characterized by culture-dependent techniques. Compared to other co-occurring grasses, B. rupestre hosted a poorer mycobiome which consisted of many rare species and a few core species that differed between aerial and belowground tissues. Recurrent burnings did not affect the diversity of the endophyte assemblages, but the percentages of infection of two core species -Omnidemptus graminis and Lachnum sp. -increased significantly. The patterns observed might be explained by (1) the capacity to survive in belowground tissues during winter and rapidly spread to the shoots when the grass starts its spring growth (O. graminis), and (2) the location in belowground tissues and its resistance to stress (Lachnum sp.). Future work should address whether the enhanced taxa have a role in the expansive success of B. rupestre in these anthropized environments., MD and LM got funding through two UPNA’s doctorate scholarships. The research was supported by three projects financed by Ecoembes-SEO/Birdlife (Libera 2017), “la Caixa” Foundation and CAN foundation (LCF/PR/PR13/51080004), and the Spanish Ministry of Science and Innovation and FEDER funds (AGL2016-76035-C2-1R).

Glioblastoma is the most aggressive tumor of the central nervous system, due to its great infiltration capacity. Understanding the mechanisms that regulate the Glioblastoma invasion front is a major challenge with preeminent potential clinical relevances. In the infiltration front, the key features of tumor dynamics relate to biochemical and biomechanical aspects, which result in the extension of cellular protrusions known as tumor microtubes. The coordination of metalloproteases expression, extracellular matrix degradation, and integrin activity emerges as a leading mechanism that facilitates Glioblastoma expansion and infiltration in uncontaminated brain regions. We propose a novel multidisciplinary approach, based on in vivo experiments in Drosophila and mathematical models, that describes the dynamics of active and inactive integrins in relation to matrix metalloprotease concentration and tumor density at the Glioblastoma invasion front. The mathematical model is based on a non-linear system of evolution equations in which the mechanisms leading chemotaxis, haptotaxis, and front dynamics compete with the movement induced by the saturated flux in porous media. This approach is able to capture the relative influences of the involved agents and reproduce the formation of patterns, which drive tumor front evolution. These patterns have the value of providing biomarker information that is related to the direction of the dynamical evolution of the front and based on static measures of proteins in several tumor samples. Furthermore, we consider in our model biomechanical elements, like the tissue porosity, as indicators of the healthy tissue resistance to tumor progression., This work has been partially supported by the MINECO-Feder (Spain) research grant number RTI2018-098850-B-I00 (JS), the Junta de Andalucía (Spain) Project PY18-RT-2422 & A-FQM311-UGR18 (MC, SCT, JS), and by the MINECO Feder (Spain by the project PID2019-110116GBI00 (SCT). This research has been partially supported by the Basque Government through the BERC 2018- 2021 program and by the Spanish State Research Agency through BCAM Severo Ochoa excellence accreditation SEV 2017-0718(MC). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 713673 (MC). The project that gave rise to these results received the support of a fellowship from “la Caixa” Foundation (ID 100010434), fellowship code is LCF/BQ/IN17/11620056 (MC). This research was also funded by the Consejería de Economía, Conocimiento, Empresas y Universidad and European Regional Development Fund (ERDF), ref. SOMM17/6109/UGR (JS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

9 pags., 7 figs., 1 tab., Adenovirus minor coat protein VI contains a membrane-disrupting peptide that is inactive when VI is bound to hexon trimers. Protein VI must be released during entry to ensure endosome escape. Hexon:VI stoichiometry has been uncertain, and only fragments of VI have been identified in the virion structure. Recent findings suggest an unexpected relationship between VI and the major core protein, VII. According to the high-resolution structure of the mature virion, VI and VII may compete for the same binding site in hexon; and noninfectious human adenovirus type 5 particles assembled in the absence of VII (Ad5-VII-) are deficient in proteolytic maturation of protein VI and endosome escape. Here we show that Ad5-VII- particles are trapped in the endosome because they fail to increase VI exposure during entry. This failure was not due to increased particle stability, because capsid disruption happened at lower thermal or mechanical stress in Ad5-VII- compared to wild-type (Ad5-wt) particles. Cryoelectron microscopy difference maps indicated that VII can occupy the same binding pocket as VI in all hexon monomers, strongly arguing for binding competition. In the Ad5-VII- map, density corresponding to the immature amino-terminal region of VI indicates that in the absence of VII the lytic peptide is trapped inside the hexon cavity, and clarifies the hexon:VI stoichiometry conundrum. We propose a model where dynamic competition between proteins VI and VII for hexon binding facilitates the complete maturation of VI, and is responsible for releasing the lytic protein from the hexon cavity during entry and stepwise uncoating, We thank the Centro Nacional de Biotecnología and the Centro de Investigaciones Biológicas cryoelectron microscopy facility for data acquisition.This work was supported by Grant BFU2016-74868-P, cofunded by the Spanish State Research Agency and the European Regional Development Fund (to C.S.M.); as well as by grants from the Spanish Ministry of Economy, Industry and Competitiveness BIO2015-68990-REDT (the Spanish Adenovirus Network, AdenoNet) (to C.S.M.), FIS2017-89549-R, “María de Maeztu” Program for Units of Excellence in R&D (MDM-2014-0377), and FIS2017-90701-REDT (to P.J.d.P.). P.H. was funded by National Institutes of Health Grants CA122677 and AI102577. U.F.G. and M.S. were funded by the Swiss National Science Foundation (SNSF 31003A_179256/1) and the Swiss National Science Foundation program Sinergia (CRSII5_170929/1). M.M. was funded by Grant BFU2015-70052R (Spanish Ministry of Economy, Industry and Competitiveness and European Regional Development Fund) and the Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, an initiative from the Spanish Institute of Health Carlos III. M.H.-P. is a recipient of a Juan de la Cierva postdoctoral contract funded by the Spanish State Research Agency. M.P.-I. holds a predoctoral contract from La Caixa Foundation.

Cellular prion protein (PrP) is largely responsible for transmissible spongiform encephalopathies (TSEs) when it becomes the abnormally processed and protease resistant form PrP. Physiological functions of PrP include protective roles against oxidative stress and excitotoxicity. Relevantly, PrP downregulates tau levels, whose accumulation and modification are a hallmark in the advance of Alzheimer’s disease (AD). In addition to the accumulation of misfolded proteins, in the initial stages of AD-affected brains display both increased reactive oxygen species (ROS) markers and levels of PrP. However, the factors responsible for the upregulation of PrP are unknown. Thus, the aim of this study was to uncover the different molecular actors promoting PrP overexpression. In order to mimic early stages of AD, we used β-amyloid-derived diffusible ligands (ADDLs) and tau cellular treatments, as well as ROS generation, to elucidate their particular roles in human PRNP promoter activity. In addition, we used specific chemical inhibitors and site-specific mutations of the PRNP promoter sequence to analyze the contribution of the main transcription factors involved in PRNP transcription under the analyzed conditions. Our results revealed that tau is a new modulator of PrP expression independently of ADDL treatment and ROS levels. Lastly, we discovered that the JNK/c-jun-AP-1 pathway is involved in increased PRNP transcription activity by tau but not in the promoter response to ROS., PRPSEM with reference (RTI2018-099773-B-I00) and PRIONET (AGL2017-90665-REDT), the Generalitat de Catalunya (SGR2017-648), CIBERNED (CNED-2018-2), and CERCA Programme/Generalitat de Catalunya to JADR. The project leading to these results also received funding from “la Caixa” Foundation (ID 100010434) under the agreement LCF/PR/HR19/52160007 and María de Maeztu Unit of Excellence (Institute of Neurosciences, University of Barcelona

17 pags., 4 figs. -- https://doi.org/10.1371/journal.pbio.3001198.g001 (fig. 1) ; https://doi.org/10.1371/journal.pbio.3001198.g002 (fig. 2) ; https://doi.org/10.1371/journal.pbio.3001198.g003 (fig. 3) ; https://doi.org/10.1371/journal.pbio.3001198.g004 (fig. 4) ; https://doi.org/10.1371/journal.pbio.3001198.s005 (numerical data), Transactive response DNA-binding Protein of 43 kDa (TDP-43) assembles various aggregate forms, including biomolecular condensates or functional and pathological amyloids, with roles in disparate scenarios (e.g., muscle regeneration versus neurodegeneration). The link between condensates and fibrils remains unclear, just as the factors controlling conformational transitions within these aggregate species: Salt- or RNA-induced droplets may evolve into fibrils or remain in the droplet form, suggesting distinct end point species of different aggregation pathways. Using microscopy and NMR methods, we unexpectedly observed in vitro droplet formation in the absence of salts or RNAs and provided visual evidence for fibrillization at the droplet surface/solvent interface but not the droplet interior. Our NMR analyses unambiguously uncovered a distinct amyloid conformation in which Phe-Gly motifs are key elements of the reconstituted fibril form, suggesting a pivotal role for these residues in creating the fibril core. This contrasts the minor participation of Phe-Gly motifs in initiation of the droplet form. Our results point to an intrinsic (i.e., non-induced) aggregation pathway that may exist over a broad range of conditions and illustrate structural features that distinguishes between aggregate forms., This work has been funded by Grants CTQ2017-84371-P to D.P.-U. and SAF2016-76678-C2-2-R to D.V.L., from the Spanish MINECO; Grant MCB1412253 from the U. S. National Science Foundation to A.E.M; AriSLA (PathensTDP project) to E.B.; and Grant LCF/BQ/PR19/11700003 from La Caixa Foundation (ID 100010434) to M.M. M.M. is a Ramón y Cajal Fellow of the Spanish AEI-Ministry of Science and Innovation (RYC2019-026574-I). NMR experiments were performed in the “Manuel Rico” NMR Laboratory (LMR) of the Spanish National Research Council (CSIC), a node of the Spanish Large-Scale National Facility (ICTS R-LRB).

Changing environments pose a challenge to living organisms. Cells need to gather and process incoming information, adapting to changes in predictable ways. This requires in particular the presence of memory, which allows different internal states to be stored. Biological memory can be stored by switches that retain information on past and present events. Synthetic biologists have implemented a number of memory devices for biological applications, mostly in single cells. It has been shown that the use of multicellular consortia provides interesting advantages to implement biological circuits. Here we show how to build a synthetic biological memory switch using an eukaryotic consortium. We engineered yeast cells that can communicate and retain memory of changes in the extracellular environment. These cells were able to produce and secrete a pheromone and sense a different pheromone following NOT logic. When the two strains were cocultured, they behaved as a double-negative-feedback motif with memory. In addition, we showed that memory can be effectively changed by the use of external inputs. Further optimization of these modules and addition of other cells could lead to new multicellular circuits that exhibit memory over a broad range of biological inputs., A.U. is a recipient of a La Caixa Fellowship. This work was supported by ERC Advanced Grant 294294 from the EU Seventh Framework Programme (SYNCOM) to R.S. and F.P., the Santa Fe Institute and AGAUR to R.S., and funding from the La Caixa Foundation in collaboration with the Centre per a la Innovació de la Diabetis Infantil Sant Joan de Déu (CIDI). The laboratories of F.P. and R.S. are also supported by Fundación Botín and by Banco Santander through its Santander Universities Global Division. The laboratory of F.P. and E.d.N. is supported by grants from the Spanish Government (BFU2015-64437-P and FEDER to F.P.; BFU2014-52333-P and FEDER to E.d.N.) and the Catalan Government (2014 SGR 599). E.d.N. and F.P. are recipients of an ICREA Acadèmia (Generalitat de Catalunya).