Current Density Functional Theory for one-dimensional fermions

The frequency-dependent response of a one-dimensional fermion system is investigated using Current Density Functional Theory (CDFT) within the local approximation (LDA). DFT-LDA, and in particular CDFT-LDA, reproduces very well the dispersion of the collective excitations. Unsurprisingly, however, the approximation fails for details of the dynamic response for large wavevectors. In particular, we introduce CDFT for the one-dimensional spinless fermion model with nearest-neighbor interaction, and use CDFT-LDA plus exact (Bethe ansatz) results for the groundstate energy as function of particle density and boundary phase to determine the linear response. The successes and failures of this approach are discussed in detail

VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad

Acta de congresoLa conmemoración de los cien años de la Reforma Universitaria de 1918 se presentó como una ocasión propicia para debatir el rol de la historia, la teoría y la crítica en la formación y en la práctica profesional de diseñadores, arquitectos y urbanistas. En ese marco el VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad constituyó un espacio de intercambio y reflexión cuya realización ha sido posible gracias a la colaboración entre Facultades de Arquitectura, Urbanismo y Diseño de la Universidad Nacional y la Facultad de Arquitectura de la Universidad Católica de Córdoba, contando además con la activa participación de mayoría de las Facultades, Centros e Institutos de Historia de la Arquitectura del país y la región. Orientado en su convocatoria tanto a docentes como a estudiantes de Arquitectura y Diseño Industrial de todos los niveles de la FAUD-UNC promovió el debate de ideas a partir de experiencias concretas en instancias tales como mesas temáticas de carácter interdisciplinario, que adoptaron la modalidad de presentación de ponencias, entre otras actividades. En el ámbito de VIII Encuentro, desarrollado en la sede Ciudad Universitaria de Córdoba, se desplegaron numerosas posiciones sobre la enseñanza, la investigación y la formación en historia, teoría y crítica del diseño, la arquitectura y la ciudad; sumándose el aporte realizado a través de sus respectivas conferencias de Ana Clarisa Agüero, Bibiana Cicutti, Fernando Aliata y Alberto Petrina. El conjunto de ponencias que se publican en este Repositorio de la UNC son el resultado de dos intensas jornadas de exposiciones, cuyos contenidos han posibilitado actualizar viejos dilemas y promover nuevos debates. El evento recibió el apoyo de las autoridades de la FAUD-UNC, en especial de la Secretaría de Investigación y de la Biblioteca de nuestra casa, como así también de la Facultad de Arquitectura de la UCC; va para todos ellos un especial agradecimiento

Role of Tenascin-X in latent TGF beta activation

La Ténascine-X (TNX) est une glycoprotéine architecturale de la matrice extracellulaire. Outre ce rôle, la TNX est également considérée comme une protéine matricellulaire qui est capable de réguler le comportement de cellules normales et tumorales. Toutefois, aucun mécanisme moléculaire et cellulaire ne permettait d'expliquer les effets cellulaires de la TNX, avant notre étude. Au laboratoire, nous avons démontré que le domaine C-terminal de type fibrinogène (FBG) de la TNX était capable d'induire l'activation du Transforming Growth Factor (TGF) bêta latent. En effet, les trois isoformes du TGF bêta sont sécrétées sous la forme de complexes inactifs formés à partir de liaisons non covalentes entre le TGF bêta mature et son propeptide N-terminal LAP (Latency Associated Peptide). Nous avons montré que le domaine FBG de la TNX interagissait physiquement avec le TGF bêta latent, in vitro et in vivo, et induisait un changement de conformation du complexe latent, afin de permettre son activation en une molécule bioactive. De plus, nous avons identifié l'intégrine alpha11 bêta1 comme un récepteur membranaire pour la TNX et nous avons montré que cette intégrine était cruciale pour le processus d'activation du TGF bêta latent par le domaine FBG. Nous avons également démontré que les Méprines alpha et bêta deux protéases de la famille des astacines, pouvaient cliver la TNX, permettant ainsi de libérer des fragments contenant le domaine FBG, capables d'activer le TGF bêta latent. Enfin, nous avons entamé une étude de la pertinence biologique de l'activation du TGF bêta latent par la TNX in vivo en analysant la voie de signalisation du TGF bêta dans des souris déficientes ou non en TNXTenascin-X (TNX) is an architectural glycoprotein of the extracellular matrix. Beyond this role, TNX is also considered as a matricellular protein that is able to regulate the behavior of normal and tumor cells. However, no molecular and cellular mechanism has been described to explain TNX cellular effects before our study. In the laboratory, we showed that the C-terminal fibrinogen-like domain (FBG) of TNX was able to induce the latent transforming growth factor (TGF beta activation. Indeed, the three TGF beta isoforms are secreted as inactive complexes formed from non-covalent bonds between the mature TGF beta and its N-terminal propeptide, called LAP (Latency Associated Peptide). We showed that the FBG domain of TNX physically interacted with the latent TGF beta, in vitro and in vivo, and induced a conformational change of the latent complex to allow its activation into a bioactive molecule. Furthermore, we identified alpha1 beta1 integrin as a cell-surface receptor for TNX and showed that this integrin was crucial for the FBG-induced latent TGF beta activation. We also demonstrated that Meprins alpha and beta, two proteases belonging to the astacin family, could cleave the TNX, thereby releasing fragments containing the FBG domain capable of activating latent TGF beta. Finally, we have initiated a study regarding the biological relevance of latent TGF beta activation by TNX in vivo by analyzing the TGF beta signaling pathway in wild type or TNX-deficient mic

Analysis of Epithelial-Mesenchymal Transition Induced by Transforming Growth Factor beta

International audienceIn recent years, the importance of the cell biological process of epithelial-mesenchymal transition (EMT) has been established via an exponentially growing number of reports. EMT has been documented during embryonic development, tissue fibrosis, and cancer progression in vitro, in animal models in vivo and in human specimens. EMT relates to many molecular and cellular alterations that occur when epithelial cells undergo a switch in differentiation that generates mesenchymal-like cells with newly acquired migratory and invasive properties. In addition, EMT relates to a nuclear reprogramming similar to the one occurring in the generation of induced pluripotent stem cells. Via such a process, EMT is gradually established to promote the generation and maintenance of adult tissue stem cells which under disease states such as cancer, are known as cancer stem cells. EMT is induced by developmental growth factors, oncogenes, radiation, and hypoxia. A prominent growth factor that causes EMT is transforming growth factor beta (TGF-beta).A series of molecular and cellular techniques can be applied to define and characterize the state of EMT in diverse biological samples. These methods range from DNA and RNA-based techniques that measure the expression of key EMT regulators and markers of epithelial or mesenchymal differentiation to functional assays of cell mobility, invasiveness and in vitro stemness. This chapter focuses on EMT induced by TGF-beta and provides authoritative protocols and relevant reagents and citations of key publications aiming at assisting newcomers that enter this prolific area of biomedical sciences, and offering a useful reference tool to pioneers and aficionados of the fiel

Prospective changes in neural alcohol cue reactivity in at-risk adolescents.

Adolescence represents an ideal time for elucidating the etiology of cue reactivity profiles. This study examined the influence of three risk factors consistently associated with heavy adolescent drinking on alcohol cue reactivity. Youth were first assessed while still naïve to alcohol (12-14 years old) and followed after transitioning into alcohol use (17-21 years old). The effects of family history of substance use disorder, sex, and history of early of dating (i.e., before 14 years of age) on BOLD response contrast to alcohol picture cues were examined in a linear mixed model, controlling for age and alcohol use patterns at follow-up. Activation to alcohol picture cues differed as a function of risk factor and time. At baseline, family history positive youth showed greater activation to alcohol cues than family history negative peers in the right middle occipital and anterior cingulate gyri. Youth with a history of early-dating showed greater activation to alcohol cues, compared to non-early daters, in the left anterior cingulate/white matter region. Girls showed greater activation to alcohol than boys at baseline in left middle frontal gyrus. At follow-up, after drinking started, patterns reversed for each risk factor. These results indicate that even prior to initiating alcohol use, adolescents showed differences in activation to alcohol cues based on their family history, dating history, and sex

Latent TGF-β Activation Is a Hallmark of the Tenascin Family

International audienceTransforming growth factor-β (TGF-β) isoforms are secreted as inactive complexes formed through non-covalent interactions between bioactive TGF-β entities and their N-terminal pro-domains called latency-associated peptides (LAP). Extracellular activation of latent TGF-β within this complex is a crucial step in the regulation of TGF-β activity for tissue homeostasis and immune cell function. We previously showed that the matrix glycoprotein Tenascin-X (TN-X) interacted with the small latent TGF-β complex and triggered the activation of the latent cytokine into a bioactive TGF-β. This activation most likely occurs through a conformational change within the latent TGF-β complex and requires the C-terminal fibrinogen-like (FBG) domain of the glycoprotein. As the FBG-like domain is highly conserved among the Tenascin family members, we hypothesized that Tenascin-C (TN-C), Tenascin-R (TN-R) and Tenascin-W (TN-W) might share with TN-X the ability to regulate TGF-β bioavailability through their C-terminal domain. Here, we demonstrate that purified recombinant full-length Tenascins associate with the small latent TGF-β complex through their FBG-like domains. This association promotes activation of the latent cytokine and subsequent TGF-β cell responses in mammary epithelial cells, such as cytostasis and epithelial-to-mesenchymal transition (EMT). Considering the pleiotropic role of TGF-β in numerous physiological and pathological contexts, our data indicate a novel common function for the Tenascin family in the regulation of tissue homeostasis under healthy and pathological conditions

Co-Expression of Androgen Receptor and Cathepsin D Defines a Triple-Negative Breast Cancer Subgroup with Poorer Overall Survival

International audienceBackground: In the triple-negative breast cancer (TNBC) group, the luminal androgen receptor subtype is characterized by expression of androgen receptor (AR) and lack of estrogen receptor and cytokeratin 5/6 expression. Cathepsin D (Cath-D) is overproduced and hypersecreted by breast cancer (BC) cells and is a poor prognostic marker. We recently showed that in TNBC, Cath-D is a potential target for antibody-based therapy. This study evaluated the frequency of AR/Cath-D co-expression and its prognostic value in a large series of patients with non-metastatic TNBC. Methods: AR and Cath-D expression was evaluated by immunohistochemistry in 147 non-metastatic TNBC. The threshold for AR positivity (AR+) was set at ≥1% of stained cells, and the threshold for Cath-D positivity (Cath-D+) was moderate/strong staining intensity. Lymphocyte density, macrophage infiltration, PD-L1 and programmed cell death (PD-1) expression were assessed. Results: Scarff-Bloom-Richardson grade 1–2 and lymph node invasion were more frequent, while macrophage infiltration was less frequent in AR+/Cath-D+ tumors (62.7%). In multivariate analyses, higher tumor size, no adjuvant chemotherapy and AR/Cath-D co-expression were independent prognostic factors of worse overall survival. Conclusions: AR/Cath-D co-expression independently predicted overall survival. Patients with TNBC in which AR and Cath-D are co-expressed could be eligible for combinatory therapy with androgen antagonists and anti-Cath-D human antibodies

SPARC in cancer‐associated fibroblasts is an independent poor prognostic factor in non‐metastatic triple‐negative breast cancer and exhibits pro‐tumor activity

International audienceTriple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and lacks specific targeted therapeutic agents. The current mechanistic evidence from cell-based studies suggests that the matricellular protein SPARC has a tumor-promoting role in TNBC; however, data on the clinical relevance of SPARC expression/secretion by tumor and stromal cells in TNBC are limited. Here, we analyzed by immunohistochemistry the prognostic value of tumor and stromal cell SPARC expression in 148 patients with non-metastatic TNBC and long follow-up (median: 5.4 years). We also quantified PD-L1 and PD-1 expression. We detected SPARC expression in tumor cells (42.4%), cancer-associated fibroblasts (CAFs; 88.1%), tumor-associated macrophages (77.1%), endothelial cells (75.2%), and tumor-infiltrating lymphocytes (9.8%). Recurrence-free survival was significantly lower in patients with SPARC-expressing CAFs. Multivariate analysis showed that SPARC expression in CAFs was an independent prognostic factor. We also detected tumor and stromal cell SPARC expression in TNBC cytosols, and in patient-derived xenografts and cell lines. Furthermore, we analyzed publicly available single-cell mRNA sequencing data and found that in TNBC, SPARC is expressed by different CAF subpopulations, including myofibroblasts and inflammatory fibroblasts that are involved in tumor-related processes. We then showed that fibroblast-secreted SPARC had a tumor-promoting role by inhibiting TNBC cell adhesion and stimulating their motility and invasiveness. Overall, our study demonstrates that SPARC expression in CAFs is an independent prognostic marker of poor outcome in TNBC. Patients with SPARC-expressing CAFs could be eligible for anti-SPARC targeted therapy. This article is protected by copyright. All rights reserved.3634629

TIF1 Suppresses Tumor Progression by Regulating Mitotic Checkpoints and Chromosomal Stability

The transcription accessory factor TIF1γ/TRIM33/RFG7/PTC7/Ectodermin functions as a tumor suppressor that promotes development and cellular differentiation. However, its precise function in cancer has been elusive. In the present study, we report that TIF1γ inactivation causes cells to accumulate chromosomal defects, a hallmark of cancer, due to attenuations in the spindle assembly checkpoint and the post-mitotic checkpoint. TIF1γ deficiency also caused a loss of contact growth inhibition and increased anchorage-independent growth in vitro and in vivo. Clinically, reduced TIF1γ expression in human tumors correlated with an increased rate of genomic rearrangements. Overall, our work indicates that TIF1γ exerts its tumor-suppressive functions in part by promoting chromosomal stability