Regularización extraordinaria de los migrantes durante el Covid-19 : América del Sur y Europa del Sur - un análisis comparativo

Las regularizaciones extraordinarias de los migrantes aparecen en la agenda de muchos países, no solo en Europa sino también en América del Sur, aunque estos procesos siempre son excepcionales, permiten legalizar en un tiempo corto, un amplio número de migrantes. Durante el Covid-19 las fronteras permanecieron cerradas, así los flujos migratorios se vieron obligados a ingresar por pasos fronterizos no habilitados, lo cual, está causando una crisis humanitaria en varios países. Adicionalmente, las autoridades han tenido que enfrentar el desempleo, la irregularidad (visas vencidas y migrantes indocumentados), y la vacunación de los migrantes. Este estudio tiene como objetivo principal analizar y comparar las regularizaciones extraordinarias de los migrantes en América del Sur, y Europa del Sur. El análisis compara seis países, enfocándose principalmente, en aquellos afectados por la migración venezolana (Chile, Colombia y Perú) en América del Sur, conjuntamente 3 países europeos fueron elegidos (España, Italia y Portugal). Adicionalmente el estudio sugiere cambios importantes, que sumados con las estadísticas disponibles y otros datos permiten analizar las tendencias migratorias y los procesos de regularización de los migrantes durante el Covid-19. Extraordinary regularizations of migrants appear on the agenda of many countries, not only in Europe but also within South America. Although these processes are always exceptional, they allow legalizing in a short of time a large number of migrants. During Covid-19 the borders remained closed. Consequently, migratory flows were forced to enter through non-authorized borders, causing a humanitarian crisis in several countries. Additionally, the authorities have had to deal with unemployment, irregularity (expired visas, undocumented migrants), and the vaccination of migrants. This study's primary objective is to analyze and compare the extraordinary regularizations of migrants in South America and Southern Europe. The analysis compares six countries, focusing mainly on countries affected by Venezuelan migration (Chile, Colombia, and Peru) in South America, and 3 European countries (Spain, Italy, and Portugal). Furthermore, important changes are suggested in the study, which, together with the available statistics and other data, allow for the analysis of migration trends and the regularization processes of migrants during Covid-19

Regularización extraordinaria de los migrantes durante el Covid-19: América del Sur y Europa del Sur – un análisis comparativo

Extraordinary regularizations of migrants appear on the agenda of many countries, not only in Europe but also within South America. Although these processes are always exceptional, they allow legalizing in a short of time a large number of migrants. During Covid-19 the borders remained closed. Consequently, migratory flows were forced to enter through non-authorized borders, causing a humanitarian crisis in several countries. Additionally, the authorities have had to deal with unemployment, irregularity (expired visas, undocumented migrants), and the vaccination of migrants. This study's primary objective is to analyze and compare the extraordinary regularizations of migrants in South America and Southern Europe. The analysis compares six countries, focusing mainly on countries affected by Venezuelan migration (Chile, Colombia, and Peru) in South America, and 3 European countries (Spain, Italy, and Portugal). Furthermore, important changes are suggested in the study, which, together with the available statistics and other data, allow for the analysis of migration trends and the regularization processes of migrants during Covid-19.Las regularizaciones extraordinarias de los migrantes aparecen en la agenda de muchos países, no solo en Europa sino también en América del Sur, aunque estos procesos siempre son excepcionales, permiten legalizar en un tiempo corto, un amplio número de migrantes. Durante el Covid-19 las fronteras permanecieron cerradas, así los flujos migratorios se vieron obligados a ingresar por pasos fronterizos no habilitados, lo cual, está causando una crisis humanitaria en varios países. Adicionalmente, las autoridades han tenido que enfrentar el desempleo, la irregularidad (visas vencidas y migrantes indocumentados), y la vacunación de los migrantes. Este estudio tiene como objetivo principal analizar y comparar las regularizaciones extraordinarias de los migrantes en América del Sur, y Europa del Sur. El análisis compara seis países, enfocándose principalmente, en aquellos afectados por la migración venezolana (Chile, Colombia y Perú) en América del Sur, conjuntamente 3 países europeos fueron elegidos (España, Italia y Portugal). Adicionalmente el estudio sugiere cambios importantes, que sumados con las estadísticas disponibles y otros datos permiten analizar las tendencias migratorias y los procesos de regularización de los migrantes durante el Covid-19

Tissue Transglutaminase Is an Integrin-Binding Adhesion Coreceptor for Fibronectin

The protein cross-linking enzyme tissue transglutaminase binds in vitro with high affinity to fibronectin via its 42-kD gelatin-binding domain. Here we report that cell surface transglutaminase mediates adhesion and spreading of cells on the 42-kD fibronectin fragment, which lacks integrin-binding motifs. Overexpression of tissue transglutaminase increases its amount on the cell surface, enhances adhesion and spreading on fibronectin and its 42-kD fragment, enlarges focal adhesions, and amplifies adhesion-dependent phosphorylation of focal adhesion kinase. These effects are specific for tissue transglutaminase and are not shared by its functional homologue, a catalytic subunit of factor XIII. Adhesive function of tissue transglutaminase does not require its cross-linking activity but depends on its stable noncovalent association with integrins. Transglutaminase interacts directly with multiple integrins of β1 and β3 subfamilies, but not with β2 integrins. Complexes of transglutaminase with integrins are formed inside the cell during biosynthesis and accumulate on the surface and in focal adhesions. Together our results demonstrate that tissue transglutaminase mediates the interaction of integrins with fibronectin, thereby acting as an integrin-associated coreceptor to promote cell adhesion and spreading

Transglutaminase 2 interacts with syndecan-4 and CD44 at the surface of human macrophages to promote removal of apoptotic cells

Tissue transglutaminase (TG2) is a multifunctional protein cross-linking enzyme that has been implicated in apoptotic cell clearance but is also important in many other cell functions including cell adhesion, migration and monocyte to macrophage differentiation. Cell surface-associated TG2 regulates cell adhesion and migration, via its association with receptors such as syndecan-4 and β1 and β3 integrins. Whilst defective apoptotic cell clearance has been described in TG2-deficient mice, the precise role of TG2 in apoptotic cell clearance remains ill-defined. Our work addresses the role of macrophage extracellular TG2 in apoptotic cell corpse clearance. Here we reveal TG2 expression and activity (cytosolic and cell surface) in human macrophages and demonstrate that inhibitors of protein crosslinking activity reduce macrophage clearance of dying cells. We show also that cell-impermeable TG2 inhibitors significantly inhibit the ability of macrophages to migrate and clear apoptotic cells through reduced macrophage recruitment to, and binding of, apoptotic cells. Association studies reveal TG2-syndecan-4 interaction through heparan sulphate side chains, and knockdown of syndecan-4 reduces cell surface TG2 activity and apoptotic cell clearance. Furthermore, inhibition of TG2 activity reduces crosslinking of CD44, reported to augment AC clearance. Thus our data define a role for TG2 activity at the surface of human macrophages in multiple stages of AC clearance and we propose that TG2, in association with heparan sulphates, may exert its effect on AC clearance via a mechanism involving the crosslinking of CD44

Association of T-Zone Reticular Networks and Conduits with Ectopic Lymphoid Tissues in Mice and Humans

Ectopic or tertiary lymphoid tissues (TLTs) are often induced at sites of chronic inflammation. They typically contain various hematopoietic cell types, high endothelial venules, and follicular dendritic cells; and are organized in lymph node–like structures. Although fibroblastic stromal cells may play a role in TLT induction and persistence, they have remained poorly defined. Herein, we report that TLTs arising during inflammation in mice and humans in a variety of tissues (eg, pancreas, kidney, liver, and salivary gland) contain stromal cell networks consisting of podoplanin+ T-zone fibroblastic reticular cells (TRCs), distinct from follicular dendritic cells. Similar to lymph nodes, TRCs were present throughout T-cell–rich areas and had dendritic cells associated with them. They expressed lymphotoxin (LT) β receptor (LTβR), produced CCL21, and formed a functional conduit system. In rat insulin promoter–CXCL13–transgenic pancreas, the maintenance of TRC networks and conduits was partially dependent on LTβR and on lymphoid tissue inducer cells expressing LTβR ligands. In conclusion, TRCs and conduits are hallmarks of secondary lymphoid organs and of well-developed TLTs, in both mice and humans, and are likely to act as important scaffold and organizer cells of the T-cell–rich zone

Expression profiling with RNA from formalin-fixed, paraffin-embedded material

<p>Abstract</p> <p>Background</p> <p>Molecular characterization of breast and other cancers by gene expression profiling has corroborated existing classifications and revealed novel subtypes. Most profiling studies are based on fresh frozen (FF) tumor material which is available only for a limited number of samples while thousands of tumor samples exist as formalin-fixed, paraffin-embedded (FFPE) blocks. Unfortunately, RNA derived of FFPE material is fragmented and chemically modified impairing expression measurements by standard procedures. Robust protocols for isolation of RNA from FFPE material suitable for stable and reproducible measurement of gene expression (e.g. by quantitative reverse transcriptase PCR, QPCR) remain a major challenge.</p> <p>Results</p> <p>We present a simple procedure for RNA isolation from FFPE material of diagnostic samples. The RNA is suitable for expression measurement by QPCR when used in combination with an optimized cDNA synthesis protocol and TaqMan assays specific for short amplicons. The FFPE derived RNA was compared to intact RNA isolated from the same tumors. Preliminary scores were computed from genes related to the ER response, HER2 signaling and proliferation. Correlation coefficients between intact and partially fragmented RNA from FFPE material were 0.83 to 0.97.</p> <p>Conclusion</p> <p>We developed a simple and robust method for isolating RNA from FFPE material. The RNA can be used for gene expression profiling. Expression measurements from several genes can be combined to robust scores representing the hormonal or the proliferation status of the tumor.</p

Transglutaminase 2 at the Crossroads between Cell Death and Survival

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Protein crosslinking in assembly and remodelling of extracellular matrices: the role of transglutaminases

Transglutaminases form a family of proteins that have evolved for specialized functions such as protein crosslinking in haemostasis, semen coagulation, or keratinocyte cornified envelope formation. In contrast to the other members of this protein family, tissue transglutaminase is a multifunctional enzyme apparently involved in very disparate biological processes. By virtue of its reciprocal Ca2+-dependent crosslinking activity or GTP-dependent signal transducing activity, tissue transglutaminase exhibits true multifunctionality at the molecular level. The crosslinking activity can subserve disparate biological phenomena depending on the location of the target proteins. Intracellular activation of tissue transglutaminase can give rise to crosslinked protein envelopes in apoptotic cells, whereas extracellular activation contributes to stabilization of the extracellular matrix and promotes cell-substrate interaction. While tissue transglutaminase synthesis and activation is normally part of a protective cellular response contributing to tissue homeostasis, the enzyme has also been implicated in a number of pathological conditions including fibrosis, atherosclerosis, neurodegenerative diseases, celiac disease, and cancer metastasis. This review discusses the role of transglutaminases in extracellular matrix crosslinking with a focus on the multifunctional enzyme tissue transglutaminase