La protección de la vida familiar de las personas desplazadas, de las demandantes de asilo, de las refugiadas y de las apátridas en el Derecho Europeo

AbstractEuropean law, in response to the massive arrival of persons applying for international protection within the territory of the EU over the past decades, has been obliged to provide legislative and jurisprudential solutions to regulate this phenomenon. The changes and advances in the protection of displaced persons, asylum applicants, refugees, and stateless persons in European law and particularly EU law have therefore been constant. In this paper we analyze to which extent these changes have affected the family life of these persons.The ECtHR, in its interpretation of the Convention, in reference to all the relevant regulations of Council of Europe, has not been keen to use its case law to create direct positive obligations for the contracting parties. Its decisions are essentially based on a case-by-case analysis. If the persons concerned are able to continue their family life outside the State of reception, it considers no violation of the right to respect for family life has occurred. On the other hand, when the State fails to meet the minimum obligations of assistance, is engagedin bad practices, causes a loss of residence or nationality, or unduly interferes with the development of family life, a violation of Article 8 of the Convention exists. In EU law, reflecting the desire to create a common asylum policy, directives and regulations have rapidly succeeded one another. In case of mass influx, displaced persons have the possibility to request reunification with family members and the right to appeal the denial of these requests. With regard to asylum applicants, the new regulations include several advances in relationto the right to respect to family life. Among others, the number of persons considered family members has been extended, including the relatives of underage applicants who may request family reunification; the conditions for detention have been improved, allowing for more contacts with family members and the possibility to facilitate separate accommodation to families in detention. An obligation has been introduced to carry out a personal interview with the applicant. Moreover, modifications have been implemented to improve the cooperation between national authorities at all levels, including the cooperation regarding family reunification in the case of unaccompanied minors and dependant persons, the performance of transfers, and the exchange of information when families are dispersed. In addition, assistance and support will be provided to the family members of minors who are victims of human trafficking when they find themselves within the territory of the Member States. With regard to the family members of refugees and stateless persons, these may now be granted refugee status if they find themselves in the same State as the applicant, provided the family already existed in the country of origin. Nonetheless, not on all relevant issues necessary headway was made. For instance, with regard to LGBTI families, their protection still essentially depends on the national rules of the host State, which continues to give cause to discrimination.ResumenAnte la llegada masiva en las últimas décadas de personas solicitantes de protección internacional en el territorio europeo, el Derecho Europeo ha debido encontrar respuestas legislativas y jurisprudenciales para regularla. Los cambios y avances en materia de protección de las personas desplazadas, de las demandantes de asilo, de las refugiadas y de las apátridas en el Derecho Europeo y especialmente en el derecho de la Unión Europea han sido constantes. En este trabajo se analiza hasta qué punto estos cambios han afectado la vida familiar de estas personas.El TEDH, interpretando el Convenio y sirviéndose de la normativa del Consejo de Europa en la materia, no ha querido en sus construcciones pretorianas crear obligaciones positivas directas para los Estados.Su análisis es casuístico y si las personas afectadas pueden continuar su vida familiar fuera del Estado que les ha acogido, no considera que exista ninguna violación del derecho al respeto de la vida familiar.En cambio, cuando el Estado no cumple con sus obligaciones de asistencia mínimas, realiza malas prácticas, es el causante de la pérdida deresidencia o nacionalidad o se injiere inadecuadamente en el desarrollo de la vida familiar, existe violación del artículo 8 del Convenio. En el Derecho de la Unión Europea, con la voluntad de crear una política común de asilo, Directivas y Reglamentos se han sucedido rápidamente.Las personas desplazadas en caso de afluencia masiva cuentan con la posibilidad de reagrupar a los miembros de la familia y de interponer recurso ante la denegación de su derecho a la reunificación familiar.En relación con los demandantes de asilo, las nuevas normativas han realizado avances en el derecho al respeto de la vida familiar. Entre otros, han ampliado los sujetos considerados como miembros de la familia, incluyendo a los familiares del solicitante menor que podrá pedir reagrupación familiar; se han mejorado las condiciones de internamiento posibilitando más contactos con los familiares e incluyendo la posibilidad de facilitar a las familias internadas un alojamiento separado y se ha creado la obligación de realizar una entrevista personal con el solicitante. Asimismo, se han realizado modificaciones paramejorar la cooperación entre autoridades nacionales a todos los niveles, incluyendo la cooperación en materia de reagrupación familiar enel caso de menores no acompañados y personas dependientes, la realizaciónde traslados y el intercambio de información cuando la familia esté dispersa. Además, se prestará asistencia y apoyo a la familia de los menores víctimas de la trata de seres humanos cuando aquella se encuentre en el territorio del Estado miembros. Respecto a los miembros de las familias de las personas refugiadas y de las apátridas estas podrán ser beneficiarias del estatuto de refugiado si se encuentran en el mismo estado que el solicitante y la familia ya existía en el país de origen. Sin embargo, no se han producido todos los avances que eran necesarios. Por ejemplo, en relación con las familias LGBTI, su protección aún depende de las normas internas del Estado miembro de acogida, lo que continúa dando pie a discriminaciones.AbstractEuropean law, in response to the massive arrival of persons applying for international protection within the territory of the EU over the past decades, has been obliged to provide legislative and jurisprudential solutions to regulate this phenomenon. The changes and advances in the protection of displaced persons, asylum applicants, refugees, and stateless persons in European law and particularly EU law have therefore been constant. In this paper we analyze to which extent these changes have affected the family life of these persons.The ECtHR, in its interpretation of the Convention, in reference to all the relevant regulations of Council of Europe, has not been keen to use its case law to create direct positive obligations for the contracting parties. Its decisions are essentially based on a case-by-case analysis. If the persons concerned are able to continue their family life outside the State of reception, it considers no violation of the right to respect for family life has occurred. On the other hand, when the State fails to meet the minimum obligations of assistance, is engagedin bad practices, causes a loss of residence or nationality, or unduly interferes with the development of family life, a violation of Article 8 of the Convention exists. In EU law, reflecting the desire to create a common asylum policy, directives and regulations have rapidly succeeded one another. In case of mass influx, displaced persons have the possibility to request reunification with family members and the right to appeal the denial of these requests. With regard to asylum applicants, the new regulations include several advances in relationto the right to respect to family life. Among others, the number of persons considered family members has been extended, including the relatives of underage applicants who may request family reunification; the conditions for detention have been improved, allowing for more contacts with family members and the possibility to facilitate separate accommodation to families in detention. An obligation has been introduced to carry out a personal interview with the applicant. Moreover, modifications have been implemented to improve the cooperation between national authorities at all levels, including the cooperation regarding family reunification in the case of unaccompanied minors and dependant persons, the performance of transfers, and the exchange of information when families are dispersed. In addition, assistance and support will be provided to the family members of minors who are victims of human trafficking when they find themselves within the territory of the Member States. With regard to the family members of refugees and stateless persons, these may now be granted refugee status if they find themselves in the same State as the applicant, provided the family already existed in the country of origin. Nonetheless, not on all relevant issues necessary headway was made. For instance, with regard to LGBTI families, their protection still essentially depends on the national rules of the host State, which continues to give cause to discrimination

uPA deficiency exacerbates muscular dystrophy in MDX mice

Duchenne muscular dystrophy (DMD) is a fatal and incurable muscle degenerative disorder. We identify a function of the protease urokinase plasminogen activator (uPA) in mdx mice, a mouse model of DMD. The expression of uPA is induced in mdx dystrophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular function. Bone marrow (BM) transplantation experiments revealed a critical function for BM-derived uPA in mdx muscle repair via three mechanisms: (1) by promoting the infiltration of BM-derived inflammatory cells; (2) by preventing the excessive deposition of fibrin; and (3) by promoting myoblast migration. Interestingly, genetic loss of the uPA receptor in mdx mice did not exacerbate muscular dystrophy in mdx mice, suggesting that uPA exerts its effects independently of its receptor. These findings underscore the importance of uPA in muscular dystrophy

FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age

Tissue regeneration declines with ageing but little is known about whether this arises from changes in stem-cell heterogeneity. Here, in homeostatic skeletal muscle, we identify two quiescent stem-cell states distinguished by relative CD34 expression: CD34High, with stemness properties (genuine state), and CD34Low, committed to myogenic differentiation (primed state). The genuine-quiescent state is unexpectedly preserved into later life, succumbing only in extreme old age due to the acquisition of primed-state traits. Niche-derived IGF1-dependent Akt activation debilitates the genuine stem-cell state by imposing primed-state features via FoxO inhibition. Interventions to neutralize Akt and promote FoxO activity drive a primed-to-genuine state conversion, whereas FoxO inactivation deteriorates the genuine state at a young age, causing regenerative failure of muscle, as occurs in geriatric mice. These findings reveal transcriptional determinants of stem-cell heterogeneity that resist ageing more than previously anticipated and are only lost in extreme old age, with implications for the repair of geriatric muscle.The authors acknowledge funding from MINECO-Spain (grant no. RTI2018-096068), ERC2016-AdG-741966, LaCaixa-HEALTH-HR17-00040, MDA, UPGRADE-H2020-825825, AFM and DPP-Spain to P.M.-C; María-de-Maeztu-Program for Units of Excellence to UPF (grant no. MDM-2014-0370) and the Severo-Ochoa-Program for Centers of Excellence to CNIC (grant no. SEV-2015-0505). This work was also supported by NIAMS IRP through NIH grants nos AR041126 and AR041164 to V.S. and utilized computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov); ASI, Ricerca Finalizzata, Ateneo Sapienza to A.M.; AIRC (grant no. 23257); ASI (grant no. MARS-PRE, DC-VUM-2017-006); H2020-MSCA-RISE-2014 (645648) to M.S. and a FNR core grant (grant no. C15/BM/10397420) to A.d.S. L.G.P. was partially supported by an FPI fellowship and an EMBO fellowship (grant no. ALTF 420-2017); and S.C., X.H. and V.M. by FI, Severo-Ochoa and PFI Fellowships (Spain), respectively

La protección de la vida familiar de las personas desplazadas, de las demandantes de asilo, de las refugiadas y de las apátridas en el derecho europeo

Ante la llegada masiva en las últimas décadas de personas solicitantes de protección internacional en el territorio europeo, el Derecho Europeo ha debido encontrar respuestas legislativas y jurisprudenciales para regularla. Los cambios y avances en materia de protección de las personas desplazadas, de las demandantes de asilo, de las refugiadas y de las apátridas en el Derecho Europeo y especialmente en el derecho de la Unión Europea han sido constantes. En este trabajo se analiza hasta qué punto estos cambios han afectado la vida familiar de estas personas. El TEDH, interpretando el Convenio y sirviéndose de la normativa del Consejo de Europa en la materia, no ha querido en sus construcciones pretorianas crear obligaciones positivas directas para los Estados. Su análisis es casuístico y si las personas afectadas pueden continuar su vida familiar fuera del Estado que les ha acogido, no considera que exista ninguna violación del derecho al respeto de la vida familiar. En cambio, cuando el Estado no cumple con sus obligaciones de asistencia mínimas, realiza malas prácticas, es el causante de la pérdida de residencia o nacionalidad o se injiere inadecuadamente en el desarrollo de la vida familiar, existe violación del artículo 8 del Convenio. En el Derecho de la Unión Europea, con la voluntad de crear una política común de asilo, Directivas y Reglamentos se han sucedido rápidamente. Las personas desplazadas en caso de afluencia masiva cuentan con la posibilidad de reagrupar a los miembros de la familia y de interponer recurso ante la denegación de su derecho a la reunificación familiar. En relación con los demandantes de asilo, las nuevas normativas han realizado avances en el derecho al respeto de la vida familiar. Entre otros, han ampliado los sujetos considerados como miembros de la familia, incluyendo a los familiares del solicitante menor que podrá pedir reagrupación familiar; se han mejorado las condiciones de internamiento posibilitando más contactos con los familiares e incluyendo la posibilidad de facilitar a las familias internadas un alojamiento separado y se ha creado la obligación de realizar una entrevista personal con el solicitante. Asimismo, se han realizado modificaciones para mejorar la cooperación entre autoridades nacionales a todos los niveles, incluyendo la cooperación en materia de reagrupación familiar en el caso de menores no acompañados y personas dependientes, la realización de traslados y el intercambio de información cuando la familia esté dispersa. Además, se prestará asistencia y apoyo a la familia de los menores víctimas de la trata de seres humanos cuando aquella se encuentre en el territorio del Estado miembros. Respecto a los miembros de las familias de las personas refugiadas y de las apátridas estas podrán ser beneficiarias del estatuto de refugiado si se encuentran en el mismo estado que el solicitante y la familia ya existía en el país de origen. Sin embargo, no se han producido todos los avances que eran necesarios. Por ejemplo, en relación con las familias LGBTI, su protección aún depende de las normas internas del Estado miembro de acogida, lo que continúa dando pie a discriminaciones.European law, in response to the massive arrival of persons applying for international protection within the territory of the EU over the past decades, has been obliged to provide legislative and jurisprudential solutions to regulate this phenomenon. The changes and advances in the protection of displaced persons, asylum applicants, refugees, and stateless persons in European law and particularly EU law have therefore been constant. In this paper we analyze to which extent these changes have affected the family life of these persons. The ECtHR, in its interpretation of the Convention, in reference to all the relevant regulations of Council of Europe, has not been keen to use its case law to create direct positive obligations for the contracting parties. Its decisions are essentially based on a case-by-case analysis. If the persons concerned are able to continue their family life outside the State of reception, it considers no violation of the right to respect for family life has occurred. On the other hand, when the State fails to meet the minimum obligations of assistance, is engaged in bad practices, causes a loss of residence or nationality, or unduly interferes with the development of family life, a violation of Article 8 of the Convention exists. In EU law, reflecting the desire to create a common asylum policy, directives and regulations have rapidly succeeded one another. In case of mass influx, displaced persons have the possibility to request reunification with family members and the right to appeal the denial of these requests. With regard to asylum applicants, the new regulations include several advances in relation to the right to respect to family life. Among others, the number of persons considered family members has been extended, including the relatives of underage applicants who may request family reunification; the conditions for detention have been improved, allowing for more contacts with family members and the possibility to facilitate separate accommodation to families in detention. An obligation has been introduced to carry out a personal interview with the applicant. Moreover, modifications have been implemented to improve the cooperation between national authorities at all levels, including the cooperation regarding family reunification in the case of unaccompanied minors and dependant persons, the performance of transfers, and the exchange of information when families are dispersed. In addition, assistance and support will be provided to the family members of minors who are victims of human trafficking when they find themselves within the territory of the Member States. With regard to the family members of refugees and stateless persons, these may now be granted refugee status if they find themselves in the same State as the applicant, provided the family already existed in the country of origin. Nonetheless, not on all relevant issues necessary headway was made. For instance, with regard to LGBTI families, their protection still essentially depends on the national rules of the host State, which continues to give cause to discrimination

Characterization of Plasminogen Binding to NB4 Promyelocytic Cells Using Monoclonal Antibodies against Receptor-Induced Binding Sites in Cell-Bound Plasminogen

The NB4 promyelocytic cell line exhibits many of the characteristics of acute promyelocytic leukemia blast cells, including the translocation (15 : 17) that fuses the PML gene on chromosome 15 to the RARα gene on chromosome 17. These cells have a very high fibrinolytic capacity. In addition to a high secretion of urokinase, NB4 cells exhibit a 10-fold higher plasminogen binding capacity compared with other leukemic cell lines. When tissue-type plasminogen activator was added to acid-treated cells, plasmin generation was 20–26-fold higher than that generated by U937 cells or peripheral blood neutrophils, respectively. We found that plasminogen bound to these cells can be detected by fluorescence-activated cell sorting using an antiplasminogen monoclonal antibody that specifically reacts with this antigen when it is bound to cell surfaces. All-trans retinoid acid treatment of NB4 cells markedly decreased the binding of this monoclonal antibody. This cell line constitutes a unique model to explore plasminogen binding and activation on cell surfaces that can be modulated by all-trans retinoid acid treatment

Characterization of Plasminogen Binding to NB4 Promyelocytic Cells Using Monoclonal Antibodies against Receptor-Induced Binding Sites in Cell-Bound Plasminogen

The NB4 promyelocytic cell line exhibits many of the characteristics of acute promyelocytic leukemia blast cells, including the translocation (15 : 17) that fuses the PML gene on chromosome 15 to the RAR alpha gene on chromosome 17. These cells have a very high fibrinolytic capacity. In addition to a high secretion of urokinase, NB4 cells exhibit a 10-fold higher plasminogen binding capacity compared with other leukemic cell lines. When tissue-type plasminogen activator was added to acid-treated cells, plasmin generation was 20-26-fold higher than that generated by U937 cells or peripheral blood neutrophils, respectively. We found that plasminogen bound to these cells can be detected by fluorescence-activated cell sorting using an antiplasminogen monoclonal antibody that specifically reacts with this antigen when it is bound to cell surfaces. All-trans retinoid acid treatment of NB4 cells markedly decreased the binding of this monoclonal antibody. This cell line constitutes a unique model to explore plasminogen binding and activation on cell surfaces that can be modulated by all-trans retinoid acid treatment

Fibrogenic cell plasticity blunts tissue regeneration and aggravates muscular dystrophy

Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.The authors acknowledge funding from the Ministry of Economy and Competitiveness (MINECO)-Spain (SAF2012-38547, PI13/02512, and PLE2009-0124), Association Française Myopathies (AFM), E-Rare, Fundació Marató TV3, Muscular Dystrophy Association (MDA), European Commission Research and Innovation funding EU-FP7 (Myoage, Optistem, and Endostem), and Duchenne PP-NL. P.P. and Y.K. were partly supported by postdoctoral fellowships from AFM

Fibrogenic cell plasticity blunts tissue regeneration and aggravates muscular dystrophy

Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered tracing mice, we demonstrate that, in dystrophic muscle, specialized cells of muscular, endothelial, and hematopoietic origins gain plasticity toward a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity also was observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.The authors acknowledge funding from the Ministry of Economy and Competitiveness (MINECO)-Spain (SAF2012-38547, PI13/02512, and PLE2009-0124), Association Française Myopathies (AFM), E-Rare, Fundació Marató TV3, Muscular Dystrophy Association (MDA), European Commission Research and Innovation funding EU-FP7 (Myoage, Optistem, and Endostem), and Duchenne PP-NL. P.P. and Y.K. were partly supported by postdoctoral fellowships from AFM

p38/MKP-1-regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair

Repair of damaged tissue requires the coordinated action of inflammatory and tissue-specific cells to restore homeostasis, but the underlying regulatory mechanisms are poorly understood. In this paper, we report new roles for MKP-1 (mitogen-activated protein kinase [MAPK] phosphatase-1) in controlling macrophage phenotypic transitions necessary for appropriate muscle stem cell-dependent tissue repair. By restricting p38 MAPK activation, MKP-1 allows the early pro- to antiinflammatory macrophage transition and the later progression into a macrophage exhaustion-like state characterized by cytokine silencing, thereby permitting resolution of inflammation as tissue fully recovers. p38 hyperactivation in macrophages lacking MKP-1 induced the expression of microRNA-21 (miR-21), which in turn reduced PTEN (phosphatase and tensin homologue) levels, thereby extending AKT activation. In the absence of MKP-1, p38-induced AKT activity anticipated the acquisition of the antiinflammatory gene program and final cytokine silencing in macrophages, resulting in impaired tissue healing. Such defects were reversed by temporally controlled p38 inhibition. Conversely, miR-21-AKT interference altered homeostasis during tissue repair. This novel regulatory mechanism involving the appropriate balance of p38, MKP-1, miR-21, and AKT activities may have implications in chronic inflammatory degenerative diseases.The authors acknowledge funding from The Ministry of Science and Innovation (PLE2009-0124, SAF2009-09782, FIS-PS09/01267, and SAF2010-21682), Association Française contre les Myopathies, Fundación Marató-TV3/R-Pascual, Muscular Dystrophy Association, and European Union Seventh Framework Programme (Myoage, Optistem, and Endostem). P. Sousa-Victor was supported by a predoctoral fellowship from Fundação para a Ciência e a Tecnologi