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Nuclear envelope lamin A/C proteins are a major component of the mammalian nuclear lamina, a dense fibrous protein meshwork located in the nuclear interior. Lamin A/C proteins regulate nuclear mechanics and structure and control cellular signaling, gene transcription, epigenetic regulation, cell cycle progression, cell differentiation, and cell migration. The immune system is composed of the innate and adaptive branches. Innate immunity is mediated by myeloid cells such as neutrophils, macrophages, and dendritic cells. These cells produce a rapid and nonspecific response through phagocytosis, cytokine production, and complement activation, as well as activating adaptive immunity. Specific adaptive immunity is activated by antigen presentation by antigen presenting cells (APCs) and the cytokine microenvironment, and is mainly mediated by the cellular functions of T cells and the production of antibodies by B cells. Unlike most cell types, immune cells regulate their lamin A/C protein expression relatively rapidly to exert their functions, with expression increasing in macrophages, reducing in neutrophils, and increasing transiently in T cells. In this review, we discuss and summarize studies that have addressed the role played by lamin A/C in the functions of innate and adaptive immune cells in the context of human inflammatory and autoimmune diseases, pathogen infections, and cancer. ; Instituto de Salud Carlos III (PI17/01395) ; European Cooperation in Science and Technology (COST) (CA15214) ; Spanish Government (SEV-2015-0505) ; German Research Foundation (DFG) (FPU18/00895; FPU19/01774) ; Torres Quevedo Program (Ministerio de Economia y Competitividad (MINECO) (PTQ-15-07915) ; 5.924 JCR (2020) Q1, 67/295 Biochemistry & Molecular Biology ; 1.455 SJR (2020) Q1, 6/68 Inorganic Chemistry ; No data IDR 2020 ; UEM

A major challenge for further development of drug screening procedures, cell replacement therapies and developmental studies is the identification of expandable human stem cells able to generate the cell types needed. We have previously reported the generation of an immortalized polyclonal neural stem cell (NSC) line derived from the human fetal ventral mesencephalon (hVM1). This line has been biochemically, genetically, immunocytochemically and electrophysiologically characterized to document its usefulness as a model system for the generation of A9 dopaminergic neurons (DAn). Long-term in vivo transplantation studies in parkinsonian rats showed that the grafts do not mature evenly. We reasoned that diverse clones in the hVM1 line might have different abilities to differentiate. In the present study, we have analyzed 9 hVM1 clones selected on the basis of their TH generation potential and, based on the number of v-myc copies, v-myc down-regulation after in vitro differentiation, in vivo cell cycle exit, TH+ neuron generation and expression of a neuronal mature marker (hNSE), we selected two clones for further in vivo PD cell replacement studies. The conclusion is that homogeneity and clonality of characterized NSCs allow transplantation of cells with controlled properties, which should help in the design of long-term in vivo experiments ; This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (formerly Science and Innovation; PLE2009-0101, SAF2010-17167), Comunidad Autónoma Madrid (S2011-BMD-2336), Instituto Salud Carlos III (RETICS TerCel, RD06/0010/0009) and European Union (Excell, NMP4-SL-2008-214706). This work was also supported by an institutional grant from Foundation Ramón Areces to the Center of Molecular Biology Severo Ochoa

15 p.-8 fig. ; The intermediate filament protein vimentin constitutes a critical sensor for electrophilic and oxidative stress, which induce extensive reorganization of the vimentin cytoskeletal network. Here, we have investigated the mechanisms underlying these effects. In vitro, electrophilic lipids, including 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and 4-hydroxynonenal (HNE), directly bind to vimentin, whereas the oxidant diamide induces disulfide bond formation. Mutation of the single vimentin cysteine residue (Cys328) blunts disulfide formation and reduces lipoxidation by 15d-PGJ2, but not HNE. Preincubation with these agents differentially hinders NaClinduced filament formation by wild-type vimentin, with effects ranging from delayed elongation and increased filament diameter to severe impairment of assembly or aggregation. Conversely, the morphology of vimentin Cys328Ser filaments is mildly or not affected. Interestingly, preformed vimentin filaments are more resistant to electrophile-induced disruption, although chemical modification is not diminished, showing that vimentin (lip) oxidation prior to assembly is more deleterious. In cells, electrophiles, particularly diamide, induce a fast and drastic disruption of existing filaments, which requires the presence of Cys328. As the cellular vimentin network is under continuous remodeling, we hypothesized that vimentin exchange on filaments would be necessary for diamide-induced disruption. We confirmed that strategies reducing vimentin dynamics, as monitored by FRAP, including cysteine crosslinking and ATP synthesis inhibition, prevent diamide effect. In turn, phosphorylation may promote vimentin disassembly. Indeed, treatment with the phosphatase inhibitor calyculin A to prevent dephosphorylation intensifies electrophile-induced wild-type vimentin filament disruption. However, whereas a phosphorylation-deficient vimentin mutant is only partially protected from disorganization, Cys328Ser vimentin is virtually resistant, even in the presence of calyculin A. Together, these results indicate that modification of Cys328 and vimentin exchange are critical for electrophile-induced network disruption. ; This work was supported by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant agreement no. 675132 "Masstrplan", Grant SAF2015-68590-R from MINECO/FEDER, Spain and Instituto de Salud Carlos III/FEDER,RETIC Aradyal RD16/0006/0021. Feedback from COST Action CA15214 "EuroCellNet" is gratefully acknowledged. ; Peer reviewed

41 p.-9 fig.-1 graph. abst. ; The type III intermediate filament protein glial fibrillary acidic protein (GFAP) contributes to the homeostasis of astrocytes, where it co-polymerizes with vimentin. Conversely, alterations in GFAP assembly or degradation cause intracellular aggregates linked to astrocyte dysfunction and neurological disease. Moreover, injury and inflammation elicit extensive GFAP organization and expression changes, which underline reactive gliosis. Here we have studied GFAP as a target for modification by electrophilic inflammatory mediators. We show that the GFAP cysteine, C294, is targeted by lipoxidation by cyclopentenone prostaglandins (cyPG) in vitro and in cells. Electrophilic modification of GFAP in cells leads to a striking filament rearrangement, with retraction from the cell periphery and juxtanuclear condensation in thick bundles. Importantly, the C294S mutant is resistant to cyPG addition and filament disruption, thus highlighting the critical role of this residue as a sensor of oxidative damage. However, GFAP C294S shows defective or delayed network formation in GFAP-deficient cells, including SW13/cl.2 cells and GFAP- and vimentin-deficient primary astrocytes. Moreover, GFAP C294S does not effectively integrate with and even disrupts vimentin filaments in the short-term. Interestingly, short-spacer bifunctional cysteine crosslinking produces GFAP-vimentin heterodimers, suggesting that a certain proportion of cysteine residues from both proteins are spatially close. Collectively, these results support that the conserved cysteine residue in type III intermediate filament proteins serves as an electrophilic stress sensor and structural element. Therefore, oxidative modifications of this cysteine could contribute to GFAP disruption or aggregation in pathological situations associated with oxidative or electrophilic stress. ; This work was supported by grant SAF2015–68590-R from MINECO/FEDER, the European Union's Horizon 2020 research and innovation program under the Marie Sklowdowska-Curie grant agreement number 675132"Masstrplan", Instituto de Salud Carlos III/FEDER, RETIC Aradyal RD16/0006/0021, by Swedish Medical Research Council (11548), ALF Gothenburg (11392), Söderberg's Foundations, Hjärnfonden, Hagströmer's Foundation Millennium, and the Swedish Stroke Foundation. Álvaro Viedma is supported by the FPI Program from MINECO reference: BES-2016–076965. Interaction between MP and DPS laboratories was part of the COST Action CA15214 "EuroCellNet". ; Peer reviewed

Interstellar and circumstellar matter.-- et al. ; Planck observations at 353 GHz provide the first fully sampled maps of the polarized dust emission towards interstellar filaments and their backgrounds (i.e., the emission observed in the surroundings of the filaments). The data allow us to determine the intrinsic polarization properties of the filaments and therefore to provide insight into the structure of their magnetic field (B). We present the polarization maps of three nearby (several parsecs long) star-forming filaments of moderate column density (NH about 1022 cm-2): Musca, B211, and L1506. These three filaments are detected above the background in dust total and polarized emission. We use the spatial information to separate Stokes I, Q, and U of the filaments from those of their backgrounds, an essential step in measuring the intrinsic polarization fraction (p) and angle (ψ) of each emission component. We find that the polarization angles in the three filaments (ψfil) are coherent along their lengths and not the same as in their backgrounds (ψbg). The differences between ψfil and ψbg are 12° and 54° for Musca and L1506, respectively, and only 6° in the case of B211. These differences forMusca and L1506 are larger than the dispersions of ψ, both along the filaments and in their backgrounds. The observed changes of ψ are direct evidence of variations of the orientation of the plane of the sky (POS) projection of the magnetic field. As in previous studies, we find a decrease of several per cent in p with NH from the backgrounds to the crest of the filaments. We show that the bulk of the drop in p within the filaments cannot be explained by random fluctuations of the orientation of the magnetic field because they are too small (σψ< 10°). We recognize the degeneracy between the dust alignment efficiency (by, e.g., radiative torques) and the structure of the B-field in causing variations in p, but we argue that the decrease in p from the backgrounds to the filaments results in part from depolarization associated with the 3D structure of the B-field: both its orientation in the POS and with respect to the POS. We do not resolve the inner structure of the filaments, but at the smallest scales accessible with Planck (~0.2 pc), the observed changes of ψ and p hold information on the magnetic field structure within filaments. They show that both the mean field and its fluctuations in the filaments are different from those of their backgrounds, which points to a coupling between the matter and the B-field in the filament formation process. ; The Planck Collaboration acknowledges the support of: ESA; CNES, and CNRS/INSU-IN2P3-INP (France); ASI, CNR, and INAF (Italy); NASA and DoE (USA); STFC and UKSA (UK); CSIC, MINECO, JA and RES (Spain); Tekes, AoF, and CSC (Finland); DLR and MPG (Germany); CSA (Canada); DTU Space (Denmark); SER/SSO (Switzerland); RCN (Norway); SFI (Ireland); FCT/MCTES (Portugal); ERC and PRACE (EU). The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement No. 267934. ; Peer Reviewed

The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement No. 267934. ; Ade, P.A.R., Aghanim, N., Alves, M.I.R., Arnaud, M., Arzoumanian, D., Aumont, J., Baccigalupi, C., Banday, A.J., Barreiro, R.B., Bartolo, N., Battaner, E., Benabed, K., Benoit-Lévy, A., Bernard, J.-P., Berné, O., Bersanelli, M., Bielewicz, P., Bonaldi, A., Bonavera, L., Bond, J.R., Borrill, J., Bouchet, F.R., Boulanger, F., Bracco, A., Burigana, C., Calabrese, E., Cardoso, J.-F., Catalano, A., Chamballu, A., Chiang, H.C., Christensen, P.R., Clements, D.L., Colombi, S., Colombo, L.P.L., Combet, C., Couchot, F., Crill, B.P., Curto, A., Cuttaia, F., Danese, L., Davies, R.D., Davis, R.J., De Bernardis, P., De Rosa, A., De Zotti, G., Delabrouille, J., Dickinson, C., Diego, J.M., Donzelli, S., Doré, O., Douspis, M., Ducout, A., Dupac, X., Elsner, F., Enßlin, T.A., Eriksen, H.K., Falgarone, E., Ferrière, K., Finelli, F., Forni, O., Frailis, M., Fraisse, A.A., Franceschi, E., Frejsel, A., Galeotta, S., Galli, S., Ganga, K., Ghosh, T., Giard, M., Giraud-Héraud, Y., Gjerløw, E., González-Nuevo, J., Górski, K.M., Gregorio, A., Gruppuso, A., Guillet, V., Hansen, F.K., Hanson, D., Harrison, D.L., Hernández-Monteagudo, C., Herranz, D., Hildebrandt, S.R., Hivon, E., Hobson, M., Holmes, W.A., Huffenberger, K.M., Hurier, G., Jaffe, A.H., Jaffe, T.R., Jones, W.C., Juvela, M., Keskitalo, R., Kisner, T.S., Knoche, J., Kunz, M., Kurki-Suonio, H., Lagache, G., Lamarre, J.-M., Lasenby, A., Lawrence, C.R., Leonardi, R., Levrier, F., Liguori, M., Lilje, P.B., Linden-Vørnle, M., López-Caniego, M., Lubin, P.M., Macías-Pérez, J.F., Maffei, B., Mandolesi, N., Mangilli, A., Maris, M., Martin, P.G., Martínez-González, E., Masi, S., Matarrese, S., Mazzotta, P., Melchiorri, A., Mendes, L., Mennella, A., Migliaccio, M., Mitra, S., Miville-Deschênes, M.-A., Moneti, A., Montier, L., Morgante, G., Mortlock, D., Munshi, D., Murphy, J.A., Naselsky, P., ...

1. Recent Trends in the Wool Industry and Some Long-Term Policy Issues -- Structure and Function of the Hair Follicle -- 2. Morphogenesis of the Hair Follicle during the Ontogeny of Human Skin -- 3. Specific Keratins and their Associated Proteins as Markers for Hair Follicle Differentiation -- 4. The Dermal Papilla and Maintenance of Hair Growth -- 5. Special Biochemical Features of the Hair Follicle -- Keratin Proteins -- 6. Intermediate Filaments: Problems and Perspectives -- 7. Intermediate Filament Associated Protein of Epidermis -- 8. Variations in the Proteins of Wool and Hair -- 9. Protein Chains in Wool and Epidermal Keratin IF: Structural Features and Spatial Arrangement -- 10. Amino Acid Sequences of Wool Keratin IF Proteins -- 11. Structural Features of Keratin Intermediate Filaments -- Physiological Factors and Hair Growth -- 12. Factors Influencing Cellular Events in the Wool Follicle -- 13. The Influence of Absorbed Nutrients on Wool Growth -- 14. The Scope for Manipulation of Fermentative Digestion in the Rumen to Improve Ruminant Production -- 15. The Effect of the Drug Minoxidil on Hair Growth -- Aberrations of Hair Growth -- 16. Variations in Wool Follicle Morphology -- 17. Follicular Malfunctions and Resultant Effects on Wool Fibres -- 18. Effect of Mutations on the Proteins of Wool and Hair -- 19. Genetic Diseases, Hair Structure and Elemental Content -- Keratin Genes -- 20. The Differential Expression of Keratin Genes in Human Epidermal Cells -- 21. Sequential Changes in Gene Expression during Epidermal Differentiation -- 22. Keratin Gene Expression in Wool Fibre Development -- 23. Evolutionary Trees of Intermediate Filament Proteins -- Growth and Differentiation -- 24. Growth Factors, Cell-Cell and Cell-Matrix Interactions in Skin during Follicle Development and Growth -- 25. The Reaction-Diffusion System as a Spatial Organizer during Initiation and Development of Hair Follicles and Formation of the Fibre -- 26. The Cultured Murine Epidermal Keratinocyte and Studies of Differentiation -- 27. Cross-Linked Envelopes: Keratinocyte Transglutaminase -- 28. Desmosomal Proteins and Cytokeratins in the Hair Follicle -- Prospects for the Future -- 29. Genetic Engineering of Rumen Bacteria -- 30. Engineering Ruminai Flora for Improved Protein Quality -- 31. Potential of Transgenic Plants for Improved Amino Acid Supply for Wool Growth -- 32. Isolation of Microbial Genes for Cysteine Synthesis and Prospects for their Use in Increasing Wool Growth -- 33. The Creation of Transgenic Sheep for Increased Wool Productivity -- 34. Efficient Creation of Transgenic Sheep: The Challenge for the Cell Biologist -- 35. Priorities for Production Research -- 36. Future Problems in Wool Structure and Textile Research.