Embryonic Stem Cells Are Redirected to Non-Tumorigenic Epithelial Cell Fate by Interaction with the Mammary Microenvironment

Experiments were conducted to redirect mouse Embryonic Stem (ES) cells from a tumorigenic phenotype to a normal mammary epithelial phenotype in vivo. Mixing LacZ-labeled ES cells with normal mouse mammary epithelial cells at ratios of 1:5 and 1:50 in phosphate buffered saline and immediately inoculating them into epithelium-divested mammary fat pads of immune-compromised mice accomplished this. Our results indicate that tumorigenesis occurs only when normal mammary ductal growth is not achieved in the inoculated fat pads. When normal mammary gland growth occurs, we find ES cells (LacZ+) progeny interspersed with normal mammary cell progeny in the mammary epithelial structures. We demonstrate that these progeny, marked by LacZ expression, differentiate into multiple epithelial subtypes including steroid receptor positive luminal cells and myoepithelial cells indicating that the ES cells are capable of epithelial multipotency in this context but do not form teratomas. In addition, in secondary transplants, ES cell progeny proliferate, contribute apparently normal mammary progeny, maintain their multipotency and do not produce teratomas

Self-assembly, binding ability and magnetic properties of dicopper(ii) pyrazolenophanes

A novel series of dinuclear copper(II) pyrazolenophanes of the formula [Cu-2(mu-4-Mepz)(2)(mu-ClO4)(ClO4)(bpm)(2)] (1), [Cu-2(mu-pz)(2)(mu-H2O)(ClO4)(4,7-Me(2)phen)(2)]ClO4 center dot H2O center dot CH3CN (2), [Cu-2(mu-pz)(2)(mu-H2O)(ClO4)(3/2)(H2O)(1/2)(phen)(2)](2)[Cu-2(mu-pz)(2)(mu-ClO4)(ClO4)(2)(phen)(2)]center dot 8H(2)O (3), and [Cu-2(mu-pz)(2)(CH3CN)(2)(3,4,7,8-Me(4)phen)(2)](ClO4)(2) (4) (Hpz = pyrazole, H-4-Mepz = 4-methylpyrazole, bpm = 2,2'-bipyrimidine, phen = 1,10-phenanthroline, 4,7-Me(2)phen = 4,7-dimethyl-1,10-phenanthroline, and 3,4,7,8-Me(4)phen = 3,4,7,8-tetramethyl-1,10-phenanthroline) have been synthesized and magneto-structurally investigated. The crystal structures of 1-4 contain bis(pyrazolate)(perchlorate)-(1 and 3), bis(pyrazolate)(aqua)-(2 and 3), or bis(pyrazolate)-bridged (4) dicopper(II) entities of the metallacyclophane-type with bpm (1), 4,7-Me(2)phen (2), phen (3), and 3,4,7,8-Me(4)phen (4) as blocking bidentate ligands. All of them exhibit a saddle conformation with an overall not planar but bent, six-membered Cu-(N-N')(2)-Cu metallacyclic core with relatively short intermetallic distances across the bis(pyrazolate)(perchlorate) [r = 3.3076(5) (1) and 3.382(1) angstrom (3)], bis(pyrazolate)(aqua) [r = 3.383(1) (2) and 3.357(1) angstrom (3)], and bis(pyrazolate) bridges [r = 3.098(1) angstrom (4)]. The analyses of the variable-temperature magnetic susceptibility of 1-4 reveal the occurrence of a moderately strong antiferromagnetic coupling across the bis(pyrazolate)(perchlorate) [-J = 228 (1) and 193 cm(-1) (3)], bis(pyrazolate)(aqua) [-J = 189 (2) and 221 cm(-1) (3)], and bis(pyrazolate) bridges [-J = 197 cm(-1) (4)] (the spin Hamiltonian being defined as H = -JS(1).S-2 with S-1 = S-2 = S-Cu = 1/2).A novel series of dinuclear copper(II) pyrazolenophanes of the formula [Cu2(μ-4-Mepz)2(μ-ClO4)(ClO4)(bpm)2] (1), [Cu2(μ-pz)2(μ-H2O)(ClO4)(4,7-Me2phen)2]ClO4·H2O·CH3CN (2), [Cu2(μ-pz)2(μ-H2O)(ClO4)3/2(H2O)1/2(phen)2]2[Cu2(μ-pz)2(μ-ClO4)(ClO4)2(phen)2]·8H2O183437449COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESsem informaçãoThis work was supported by the Ministerio Español de Economía y Competitividad (Project CTQ2013-44844P and Unidad de Excelencia MDM-2015-0538) and the Generalitat Valenciana (PROMETEOII/2014/070). We also acknowledge the financial support from Brazilian

Population homogeneity for the antibody response to COVID-19 BNT162b2/Comirnaty vaccine is only reached after the second dose across all adult age ranges

ABSTRACT: While mRNA vaccines are administrated worldwide in an effort to contain the COVID-19 pandemic, the heterogeneity of the humoral immune response they induce at the population scale remains unclear. Here, in a prospective, longitudinal, cohort-study, including 1245 hospital care workers and 146 nursing home residents scheduled for BNT162b2 vaccination, together covering adult ages from 19 to 99 years, we analyse seroconversion to SARS-CoV-2 spike protein and amount of spike-specific IgG, IgM and IgA before vaccination, and 3-5 weeks after each dose. We show that immunogenicity after a single vaccine dose is biased to IgG, heterogeneous and reduced with increasing age. The second vaccine dose normalizes IgG seroconversion in all age strata. These findings indicate two dose mRNA vaccines is required to reach population scale humoral immunity. The results advocate for the interval between the two doses not to be extended, and for serological monitoring of elderly and immunosuppressed vaccinees.info:eu-repo/semantics/publishedVersio

Tumor necrosis Factor Receptor-1 (p55) deficiency attenuates tumor growth and intratumoral angiogenesis and stimulates CD8+ T cell function in melanoma

The role of tumor necrosis factor-α (TNF-α) in shaping the tumor microenvironment is ambiguous. Consistent with its uncertain role in melanoma, TNF-α plays a dual role, either acting as a cytotoxic cytokine or favoring a tumorigenic inflammatory microenvironment. TNF-α signals via two cognate receptors, namely TNFR1 (p55) and TNFR2 (p75), which mediate divergent biological activities. Here, we analyzed the impact of TNFR1 deficiency in tumor progression in the B16.F1 melanoma model. Tumors developed in mice lacking TNFR1 (TNFR1 knock-out; KO) were smaller and displayed lower proliferation compared to their wild type (WT) counterpart. Moreover, TNFR1 KO mice showed reduced tumor angiogenesis. Although no evidence of spontaneous metastases was observed, conditioned media obtained from TNFR1 KO tumors increased tumor cell migration. Whereas the analysis of tumor-associated immune cell infiltrates showed similar frequency of total and M2-polarized tumor-associated macrophages (TAMs), the percentage of CD8+ T cells was augmented in TNFR1 KO tumors. Indeed, functional ex vivo assays demonstrated that CD8+ T cells obtained from TNFR1KO mice displayed an increased cytotoxic function. Thus, lack of TNFR1 attenuates melanoma growth by modulating tumor cell proliferation, migration, angiogenesis and CD8+ T cell accumulation and activation, suggesting that interruption of TNF-TNFR1 signaling may contribute to control tumor burden.Fil: Rodriguez, Yamila Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Campos, Ludmila Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Castro, Melina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Bannoud, Nadia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Blidner, Ada Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Filippa, Verónica P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin

Algorithm Integration Behavior for Discovering Group Membership Rules

Information exploitation processes use different data mining algorithms for obtaining knowledge patterns from data obtained on the problem domain. One of the assumptions when working with these algorithms is that the complexity of the membership domain of the cases they use does not affect the quality of the obtained results. So, it is important to analyze the behavior of the information exploitation process through the discovery of group membership rules by using clustering and induction algorithms. This research characterizes the complexity of the domains in terms of the pieces of knowledge that describe them and information exploitation processes they seek to discover. The results of the experiments show that, in the case of the process for discovering group membership rules, the quality of the patterns differs depending on the algorithms used in the process and the complexity of the domains to which they are applied

Enhancement of Notch receptor maturation and signaling sensitivity by Cripto-1

Cripto-1 associates with Notch1 in the endoplasmic reticulum and Golgi to enhance Notch1 localization to lipid rafts and its maturation

Segundo Congreso Salesiano de Ciencia, Tecnología e Innovación para la Sociedad

La segunda edición del Congreso Salesiano de Ciencia, Tecnología e Innovación para la Sociedad, CITIS, realizado el 2 y 3 de diciembre de 2015 y organizado por la Universidad Politécnica Salesiana (sede Guayaquil), ofreció un espacio idóneo para la presentación, difusión e intercambio de importantes investigaciones (nacionales e internacionales) a los docentes investigadores y a la comunidad universitaria en general. Los trabajos recogidos en estas Memorias Académicas pertenecen a diferentes líneas de investigación del área de la Ingeniería: Telecomunicaciones, Automatización y Control, Procesos Industriales, Sistemas Eléctricos de Potencia, Telemática e Informática Aplicada, áreas de interés en esta segunda edición del CITIS. Cabe destacar que se evidencia la preocupación por la dimensión humana y social mediante el desarrollo responsable de la ciencia y la tecnología. La realización de este Congreso ha puesto en evidencia la importancia y pertinencia de la actividad investigativa que se genera en las universidades (en proyectos desarrollados por los docentes investigadores e, incluso, por los estudiantes de grado y posgrado), así como los altos niveles de compromiso académico y social

Therapeutic DNA vaccination of vertically HIV-infected children: Report of the first pediatric randomised trial (PEDVAC)

Subjects: Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm³. Intervention: Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Results: Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. Conclusions: The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. Trial registration: clinicaltrialsregister.eu 2007-002359-18; 2007-002359-18/I