αV-Integrins Are Required for Mechanotransduction in MDCK Epithelial Cells

The properties of epithelial cells within tissues are regulated by their immediate microenvironment, which consists of neighboring cells and the extracellular matrix (ECM). Integrin heterodimers orchestrate dynamic assembly and disassembly of cell-ECM connections and thereby convey biochemical and mechanical information from the ECM into cells. However, the specific contributions and functional hierarchy between different integrin heterodimers in the regulation of focal adhesion dynamics in epithelial cells are incompletely understood. Here, we have studied the functions of RGD-binding αV-integrins in a Madin Darby Canine Kidney (MDCK) cell model and found that αV-integrins regulate the maturation of focal adhesions (FAs) and cell spreading. αV-integrin-deficient MDCK cells bound collagen I (Col I) substrate via α2β1-integrins but failed to efficiently recruit FA components such as talin, focal adhesion kinase (FAK), vinculin and integrin-linked kinase (ILK). The apparent inability to mature α2β1-integrin-mediated FAs and link them to cellular actin cytoskeleton led to disrupted mechanotransduction in αV-integrin deficient cells seeded onto Col I substrate

Identification of a 200-kD, brefeldin-sensitive protein on Golgi membranes

A mAb AD7, raised against canine liver Golgi membranes, recognizes a novel, 200-kD protein (p200) which is found in a wide variety of cultured cell lines. Immunofluorescence staining of cultured cells with the AD7 antibody produced intense staining of p200 in the juxtanuclear Golgi complex and more diffuse staining of p200 in the cytoplasm. The p200 protein in the Golgi complex was colocalized with other Golgi proteins, including mannosidase II and beta-COP, a coatomer protein. Localization of p200 by immunoperoxidase staining at the electron microscopic level revealed concentrations of p200 at the dilated rims of Golgi cisternae. Biochemical studies showed that p200 is a peripheral membrane protein which partitions to the aqueous phase of Triton X-114 solutions and is phosphorylated. The p200 protein is located on the cytoplasmic face of membranes, since it was accessible to trypsin digestion in microsomal preparations. and is recovered in approximately equal amounts in membrane pellets and in the cytosol of homogenized cells. Immunofluorescence staining of normal rat kidney cells exposed to the toxin brefeldin A (BFA), showed that there was very rapid redistribution of p200, which was dissociated from Golgi membranes in the presence of this drug. The effect of BFA was reversible, since upon removal of the toxin, AD7 rapidly reassociated with the Golgi complex. In the BFA-resistant cell line PtK1, BFA failed to cause redistribution of p200 from Golgi membranes. Taken together, these results indicate that the p200 Golgi membrane-associated protein has many properties in common with the coatomer protein, beta-COP

Evaluation Of A Group Cognitive-Behavioral Depression Prevention Program For Young Adolescents: A Randomized Effectiveness Trial

Depression is a common psychological problem in adolescence. Recent research suggests that group cognitive-behavioral interventions can reduce and prevent symptoms of depression in youth. Few studies have tested the effectiveness of such interventions when delivered by school teachers and counselors (as opposed to research team staff). We evaluated the effectiveness of the Penn Resiliency Program for adolescents (PRP-A), a school-based group intervention that targets cognitive behavioral risk factors for depression. We randomly assigned 408 middle school students (ages 10–15) to one of three conditions: PRP-A, PRP-AP (in which adolescents participated in PRP-A and parents were invited to attend a parent intervention component), or a school-as-usual control. Adolescents completed measures of depression and anxiety symptoms, cognitive style, and coping at baseline, immediately after the intervention, and at 6-month follow-up. PRP-A reduced depression symptoms relative to the school as usual control. Baseline levels of hopelessness moderated intervention effects. Among participants with average and high levels of hopelessness, PRP (A and AP) significantly improved depression symptoms, anxiety symptoms, hopelessness, and active coping relative to control. Among participants with low baseline hopelessness, we found no intervention effects. PRP-AP was not more effective than PRP-A alone. We found no intervention effects on clinical levels of depression or anxiety. These findings suggest that cognitive-behavioral interventions can be beneficial when delivered by school teachers and counselors. These interventions may be most helpful to students with elevated hopelessness

Social representations of history, wars and politics in Latin America, Europe and Africa

This study analyzes how people perceive world history on three continents: Latin America, Europe and Africa. A total of 1179 university students form Argentina, Brazil, Peru, Portugal, Spain, Guinea-Bissau, and Cape Verde were asked to evaluate world events and leaders in terms of their valence and importance. The results demonstrated that social representations of history show a Euro/North American-centric, long-term positive evaluation, recency, and socio- centric bias. Euro/North American-centric events and leaders were found to be rated as more important and were more positively perceived in general. Distant political events, like French or American Revolution, were considered to be more positive than XX century similar events, which supports the long-term positive evaluation bias hypothesis. The hypothesis on recency bias was partially substantiated. Confirming the existence of such bias, World War II was rated as more important than the previous XX century wars and revolutions. Socio-centric bias also received partial support. African participants rated Mandela as a more important leader than other participants did. Latin Americans rated Che Guevara less positively, which suggests that some leaders are generally idealized icons, not based on group belongingness. However, results did not bring support to the centrality of war hypothesis. Wars were indeed negatively evaluated and World War II was rated as an important and negative event. Nevertheless, war- and politics-related events were not perceived as more important than the Industrial Revolution, suggesting that people appraise the importance of long-term socioeconomic factors of history when responding to close-ended quantitative measures (vs. open-ended salience measures). Results are discussed in the framework of social representations of history.El estudio analiza como las personas perciben la historia mundial en tres continentes: Latinoamérica, Europa y África. 1179 estudiantes universitarios de Argentina, Brasil, Perú, Portugal, España, Guinea-Bissau y Cabo Verde evaluaron una lista de eventos mundiales y líderes en lo que concierne a su valoración e importancia. Los resultados han mostrado que la representación social de la historia se caracteriza por un Euro centrismo, una evaluación positiva a largo plazo, y por sesgos socio-céntricos. Los eventos “Occidentales” (vinculados a Europa y Norteamérica) fueron evaluados como más importantes y percibidos más positivamente que los no-Occidentales. Eventos políticos distantes, como la Revolución Francesa o Americana, fueron evaluados más positivamente que eventos similares del siglo XX, apoyando la hipótesis de la evaluación positiva del pasado lejano. La hipótesis del sesgo de recencia o proximidad fue parcialmente confirmada, ya que la II Guerra Mundial fue evaluada como más importante que revoluciones o guerras anteriores al siglo XX. El sesgo socio-céntrico también recibe apoyo parcial. Los africanos consideraron a Mandela como un líder más importante comparado con los otros participantes. Los Latinos americanos evaluaron Che Guevara menos positivamente, lo que sugiere que ciertos líderes son generalmente íconos idealizados, y su valoración positiva no se basa en la proximidad o la pertenencia grupal. Sin embargo, los resultados no apoyaron la hipótesis de la centralidad de la guerra. Las guerras fueron efectivamente evaluadas negativamente y la II Guerra Mundial fue evaluado como la guerra más importante y como un evento muy negativo. No obstante, las guerras y eventos políticos relacionados con la violencia no fueron percibidos como más importantes que la Revolución industrial, sugiriendo que las personas valoran la importancia general de los factores históricos socioeconómicos cuando responden a medidas cuantitativas cerradas (vs. medidas abiertas). Los resultados se analizan desde el marco teórico de las representaciones sociales de la Historia

Polarization Stability and Dynamics in a Model for a Polarization-Isotropic Laser That Goes Beyond Third-Order Lamb Theory

Instabilities and dynamical pulsations are common features of solutions of a model that includes the material variable dynamics for a laser with a polarization isotropic resonator and with a homogeneously broadened j=1 --\u3e j=0 transition. These resemble in some respects features found in third-order Lamb theories under anisotropic conditions, such as splitting of the optical field into two relatively independent orthogonally polarized modes with different optical frequencies. At higher intensities the amplitudes and frequencies of these modes exhibit such strong coupling that a \u27\u27two-mode\u27\u27 description loses its usefulness or effectiveness. Various periodic attractors with strong intensity and polarization pulsations are found for moderate excitation levels. Some of these attractors preserve the breaking of the polarization isotropy on average just as does any linearly polarized solution. But in some cases the dynamics restore the polarization isotropy on average. We also find other dynamical phenomena, including periodic and apparently chaotic states, often involving rapid switching between long interludes of nearly constant polarization, and homoclinic behavior

Host Cell Transcriptome Profile during Wild-Type and Attenuated Dengue Virus Infection

10.1371/journal.pntd.0002107PLoS Neglected Tropical Diseases73

COVID-19 and migrant and refugee health: A pointer to system competence in future pandemic preparedness

COVID-19 and migrant and refugee health: A pointer to system competence in future pandemic preparednes

Interplay between estrogen receptor and AKT in estradiol-induced alternative splicing.

BACKGROUND: Alternative splicing is critical for generating complex proteomes in response to extracellular signals. Nuclear receptors including estrogen receptor alpha (ERα) and their ligands promote alternative splicing. The endogenous targets of ERα:estradiol (E2)-mediated alternative splicing and the influence of extracellular kinases that phosphorylate ERα on E2-induced splicing are unknown. METHODS: MCF-7 and its anti-estrogen derivatives were used for the majority of the assays. CD44 mini gene was used to measure the effect of E2 and AKT on alternative splicing. ExonHit array analysis was performed to identify E2 and AKT-regulated endogenous alternatively spliced apoptosis-related genes. Quantitative reverse transcription polymerase chain reaction was performed to verify alternative splicing. ERα binding to alternatively spliced genes was verified by chromatin immunoprecipitation assay. Bromodeoxyuridine incorporation-ELISA and Annexin V labeling assays were done to measure cell proliferation and apoptosis, respectively. RESULTS: We identified the targets of E2-induced alternative splicing and deconstructed some of the mechanisms surrounding E2-induced splicing by combining splice array with ERα cistrome and gene expression array. E2-induced alternatively spliced genes fall into at least two subgroups: coupled to E2-regulated transcription and ERα binding to the gene without an effect on rate of transcription. Further, AKT, which phosphorylates both ERα and splicing factors, influenced ERα:E2 dependent splicing in a gene-specific manner. Genes that are alternatively spliced include FAS/CD95, FGFR2, and AXIN-1. E2 increased the expression of FGFR2 C1 isoform but reduced C3 isoform at mRNA level. E2-induced alternative splicing of FAS and FGFR2 in MCF-7 cells correlated with resistance to FAS activation-induced apoptosis and response to keratinocyte growth factor (KGF), respectively. Resistance of MCF-7 breast cancer cells to the anti-estrogen tamoxifen was associated with ERα-dependent overexpression of FGFR2, whereas resistance to fulvestrant was associated with ERα-dependent isoform switching, which correlated with altered response to KGF. CONCLUSION: E2 may partly alter cellular proteome through alternative splicing uncoupled to its effects on transcription initiation and aberration in E2-induced alternative splicing events may influence response to anti-estrogens.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are