Mechanics of epithelial closure over non-adherent environments

International audienceThe closure of gaps within epithelia is crucial to maintain its integrity during biological processes such as wound healing and gastrulation. Depending on the distribution of extracellular matrix, gap closure occurs through assembly of multicellular actin-based contractile cables or protrusive activity of border cells into the gap. Here we show that the supracellular actomyosin contractility of cells near the gap edge exerts sufficient tension on the surrounding tissue to promote closure of non-adherent gaps. Using traction force microscopy, we observe that cell-generated forces on the substrate at the gap edge first point away from the centre of the gap and then increase in the radial direction pointing into the gap as closure proceeds. Combining with numerical simulations, we show that the increase in force relies less on localized purse-string contractility and more on large-scale remodelling of the suspended tissue around the gap. Our results provide a framework for understanding the assembly and the mechanics of cellular contractility at the tissue level

Forces driving epithelial wound healing

A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and ‘purse-string’ contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate

Mechanics of epithelial closure over non-adherent environments

The closure of gaps within epithelia is crucial to maintain its integrity during biological processes such as wound healing and gastrulation. Depending on the distribution of extracellular matrix, gap closure occurs through assembly of multicellular actin-based contractile cables or protrusive activity of border cells into the gap. Here we show that the supracellular actomyosin contractility of cells near the gap edge exerts sufficient tension on the surrounding tissue to promote closure of non-adherent gaps. Using traction force microscopy, we observe that cell-generated forces on the substrate at the gap edge first point away from the centre of the gap and then increase in the radial direction pointing into the gap as closure proceeds. Combining with numerical simulations, we show that the increase in force relies less on localized purse-string contractility and more on large-scale remodelling of the suspended tissue around the gap. Our results provide a framework for understanding the assembly and the mechanics of cellular contractility at the tissue level

A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion

Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion. N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent. Heterotypic junctions between CAFs and cancer cells are observed in patient-derived material. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion

Nuevos datos sobre el Plioceno del Baix Ebre. Aportación a la correlación entre las escalas marina y continental

[ES] Con motivo del hallazgo de nuevos yacimientos de vertebrados en los depósitos pliocénicos de las cercanías de Campredó (Baix Ebre. Tarragona), se revisan los cortes clásicos de Sant Onofre y de la Vía Férrea. La sucesión del Plioceno del Baix Ebre consta aquí de dos unidades principales. La inferior, constituída por lutitas, areniscas y conglomerados, con fauna marina ha sido atribuida por otros autores al Plioceno medio-superior de la escala marina. La unidad superior, constituida por calizas y margas con intercalaciones lignitosas de origen lacustre, ha proporcionado una fauna de micromamíferos de edad Rusciniense inferior (zona MN14 de MEIN). Desde el punto de vista de la correlación entre escalas estratigráficas esta sucesión muestra que niveles lacustres de edad Rusciniense inferior (Plioceno inferior de la escala continental) se superponen a niveles de edad Plioceno medio-superior de la escala marina.[EN] The classical sections of Sant Qnofre and Vía Férrea (Baix Ebre, Tarragona) are revised on the basis of new vertebrates found in Pliocene beds near Campredó. The Pliocene of Baix Ebre has two main units. The lower unit is formed by mudstones, sandstones and conglomerates bearing marine fauna that has been dated as Middle-Upper Pliocene (marine scale). Tlie Upper unit is formed by lacustrine marls and limestones with interbedded Iignites. Micromammals of Lower Ruscinian age (zone MN14 of MEIN) have been found in this Upper unit. Thus this section points out that lacustrine beds of Lower Ruscinian age (Lower Pliocene on the continental scale) overlai beds dated as Middle to Upper Pliocene according to the marine scale.Esta nota ha sido realizada dentro del proyecto Evolución Geodinámica de las fosas neógenas del noreste de la Península Ibérica, que se enmarca dentro del programac-4-0010-8 1 (C. S. I. C. y Com. Ass. Científ. y Técnica).Peer reviewe

La música a la ciutat de Girona (1888-1985)

La tesi és una investigació histórica que presenta el fet musical a la ciutat de Girona, i inclou una paronòmica general de la història musical de les principals poblacions de les seves comarques: Olot, Figueres, Banyoles. ripoll, La Bisbal d'Empordà, Sant Feliu de Guíxols, etc.Està organitzada metodològicament en un marc cronològic i una metodologia positivista, intentant reflexar la verdadera història de la música a la ciutat de Girona amb tots i cadascun dels seus personatges i les seves institucions.La recerca s'emmarca al voltant de les corrents artístiques i polítiques de cada moment: Modernisme, Noucentisme, República, Guerra Civil, Franquisme i Democràcia. De cadascuna d'ella s'ha investigat sobre les orquestres, les cobles i les sardanes, els grups de música de cambra, la música en els cafès, la música en la intimitat de les cases particulars, el desenvolupament laboral de la professió musical a travès de la història del Sindicat i la Mútua de Músics, les sales de ball, els cinemes amb música en directe, els crítics musicals, etc. La recerca porta a la conclusió final de què l'època de millor esplendor, de més qualitat i també quantitat de música a la ciutat i comarques, i que ha viscut un millor ambient musical en tota la història, és el període que va des de principis del segle XX fins a l'esclat de la Guerra Civil (1900-1936)The music in the city of Girona (1888-1985) is a historical research about music in the city of Girona which also includes, in its last chapter, a general view of the history of music in the main towns in the county of Girona: Olot, Figueres, Banyoles, Ripoll, La Bisbal d'Empordà, Sant Feliu de Guíxols, etc. In the first chapter we analyse the musical precedents in the city from its origins, its jugglers and troubadours, the music in the cathedral, its organists and musicians till the end of the 19th century where we do a more detailed research. In the following chapter the research is set around the artistic and political trends of each moment: Modernism, Noucentism, Republic, Civil War, Franquism and Democracy. In each of them we have investigated about the orchestras, bands, sardanes, the groups of chamber music, the music in the cafés, the music in the privacy of houses, the development of the music profession throughy the history of hte Union of musicians, the dance-halls, the cinemas with live music, the music reviewers, etc. The resarch shows that the period of highest musical quality and better atmosphere in all the history was without any doubt the period which goes the beginning of the 20th century till just before the outbreak of the Civil War (1900-1936

Nuevos datos sobre el Plioceno del Baix Ebre. Aportación a la correlación entre las escalas marina y continental.

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Geology and chronology of the continental Pleistocene archeological and paleontological sites of the Orce area (Baza basin, Spain)

The Guadix-Baza Basin hosts a continuous continental record of paleoenvironmental, paleobiological and geological changes from around 8 Ma to 205 ka. A remarkable succession of Pleistocene mammal sites is found in the Lower and Upper members of the Baza Formation in the Orce area. The Upper Member contains the Early Pleistocene paleontological and archeological sites of Barranco León-5 and Fuente Nueva 3. Both sites belong to the early Pleistocene zone defined by Allophaiomys aff. lavocati and a small Mimomys savini. This zone can be correlated with that of central Europe containing Mimomys savini and Microtus praehintoni. These sites are located in the marginal lacustrine deposits of the Baza lake system and originated in expanded phases of the main lake when meteoric surface and shallow groundwater inputs were predominant. The Barranco León-5 site is related to a sudden event of high-energy currents entering a lacustrine - palustrine domain. These currents transported gravels, bones and lithic industries from a short distance (maximum, hundreds of meters). In contrast, the diverse levels in Fuente Nueva 3 do not show evidence of noticeable transport by traction currents.The age of the mammal succession and sites is based on magnetostratigraphy. In the Middle and Upper members of the Baza Formation, only reversed polarities are found (Matuyama epoch). The location of the Olduvai chron is still unclear and could have not been recorded due to the common hiatuses observed in the sedimentary successions. In the Lower Member, normal and reverse polarities (Gauss epoch) are found in the Galera and Vélez-Salar sections. The later contains the site of Fuente Nueva 1, which is pre-Olduvai chron in age according to paleontological data and biostratigraphic correlation. © 2011.The following research projects contributed to this study: CGL2008-00594/BTE and CGL2009-7896 (Spanish Ministry of Sciences and Research), 2009 SGR 324 (Generalitat de Catalunya) and PD 3287/2009 (Dirección General de Bienes Culturales, Consejería de Cultura, Junta de Andalucía).Peer Reviewe

Magnetostratigraphy of the Lower pleistocene in the Guadix-Baza basin (Betics, Spain)

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Joint vegetation and mammalian records at the early Pleistocene sequence of Bòvila Ordis (Banyoles-Besalú Basin, NE Spain) and their bearing on early hominin occupation in Europe

The early Pleistocene site at Bòvila Ordis (Banyoles-Besalú Basin in NE Iberia) delivered in the past a significant pollen succession which can be assigned to the upper Matuyama geomagnetic chron owing to the identification of the Cobb Mountain magnetic subchron (1.2 Ma ago). It has been previously shown by palynology that the succession of lakes recorded at Bòvila Ordis corresponds to a succession of late early Pleistocene glacial–interglacial phases, between 1.2 and 1 Ma, which can be correlated with MIS 35, 33 and 31. The present investigation focuses on lake 1 (borehole BOIV) and lake 3 (boreholes BOI, BOII and BOIII and outcrops) from this site, where both fossil pollen and rodent teeth were recovered together in the same sediment, and offers the potential to provide a vegetation and climatic context to sites that are dated by rodent teeth, such as some hominin sites in Western Europe. Here we analyse the rodent content and their biostratigraphical implications in the context of early hominin dispersal in Western Europe. In lake 1, pollen data had revealed in previous analysis a complete glacial–interglacial cycle and parts of a second one. The uppermost part of BOIV sequence yielded rodent remains that can be assigned to the arvicolid species Allophaiomys chalinei and Mimomys cf. savini. Previous palynological investigations from lake 3 had revealed a temperate deciduous forest, indicative of warm and humid conditions. At the top of the section of lake 3, a regression of the forest and the spread of open landscape elements indicated drier, more steppic conditions. The palaeobiological record of lake 3 includes pollen and large (Cervus philisi, Hippopotamus antiquus and Equus stenonis) and small mammal remains (Mimomys savini and Allophaiomys lavocati). The rodent material from lake 1 clearly indicates an early Pleistocene age somewhat older than that of lake 3. According to these new biostratigraphic data in the context of previous palynological and chronological data, it is clear that Allophaiomys chalinei entered Iberia before 1 Ma ago and A. lavocati remained until 1 Ma ago. The fact that Allophaiomys lavocati and Allophaiomys chalinei, two arvicolids currently associated with the earliest evidence of hominin presence in Western Europe, appear in Bòvila Ordis at a time of mild, temperate conditions reinforce the idea that the first hominin dispersal in this region was strongly dependent on favourable climatic conditions. © 2018 Senckenberg Gesellschaft für Naturforschung and Springer-Verlag GmbH Germany, part of Springer NatureThis paper is part of projects CGL2016-80000-P (MINECO, Spain) and SGR2017-859 (Gencat). I. Lozano-Fernández was a beneficiary of a pre-doctoral grant from the Fundación Atapuerca assigned to the IPHES.Peer reviewe