CD44-high neural crest stem-like cells are associated with tumour aggressiveness and poor survival in neuroblastoma tumours

BACKGROUND: Neuroblastoma is a paediatric tumour originated from sympathoadrenal precursors and characterized by its heterogeneity and poor outcome in advanced stages. Intra-tumoral cellular heterogeneity has emerged as an important feature in neuroblastoma, with a potential major impact on tumour aggressiveness and response to therapy. CD44 is an adhesion protein involved in tumour progression, metastasis and stemness in different cancers; however, there has been controversies about the significance of CD44 expression in neuroblastoma and its relationship with tumour progression. METHODS: We have performed transcriptomic analysis on patient tumour samples studying the outcome of patients with high CD44 expression. Adhesion, invasion and proliferation assays were performed in sorted CD44high neuroblastoma cells. Tumoursphere cultures have been used to enrich in undifferentiated stem-like cells and to asses self-renewal and differentiation potential. We have finally performed in vivo tumorigenic assays on cell line-derived or Patient-derived xenografts. FINDINGS: We show that high CD44 expression is associated with low survival in high-grade human neuroblastoma, independently of MYCN amplification. CD44 is expressed in a cell population with neural crest stem-like features, and with the capacity to generate multipotent, undifferentiated tumourspheres in culture. These cells are more invasive and proliferative in vitro. CD44 positive cells obtained from tumours are more tumorigenic and metastatic, giving rise to aggressive neuroblastic tumours at high frequency upon transplantation. INTERPRETATION: We describe an unexpected intra-tumoural heterogeneity within cellular entities expressing CD44 in neuroblastoma, and propose that CD44 has a role in neural crest stem-like undifferentiated cells, which can contribute to tumorigenesis and malignancy in this type of cancer. FUNDING: Research supported by grants from the "Asociación Española contra el Cáncer" (AECC), the Spanish Ministry of Science and Innovation SAF program (SAF2016-80412-P), and the European Research Council (ERC Starting Grant to RP).Spanish Ministry of Science and Innovation SAF program (SAF2016-80412-P

Radiative recombination in Cu2ZnSnSe4 thin films with Cu deficiency and Zn excess

Thin films of Cu2ZnSnSe4 (CZTSe) with copper de�ficiency and zinc excess were fabricated at Northumbria University by the selenisation of metallic precursors deposited on Mo/glass and bare glass substrates. Absorption and photoluminescence (PL) measurements were used to examine the �film on glass whereas fi�lms on Mo/glass were used to produce a solar cell with ef�ficiency of 8.1%. Detailed temperature and excitation intensity analysis of PL spectra allows identifi�cation of the main recombination mechanisms as band-to-tail and band-to-band transitions. The latter transition was observed in the spectra from 6 to 300 K

Influencia de la fertilización nitrogenada sobre las concentraciones de K+, Mg2+ y Ca2+ y sus bioindicadores en raíces y hojas de plantas de judía

The pyruvate kinase (PK) and ATPase activities taking part in nitrogen (N) assimilation is essential for the growth and development of plants. Studies on the kinetics of these enzymes reveal that its activities are dependent of the cofactors K+, Ca2+, and Mg2+. Therefore, the objective of the present work was to determine the effect of different doses of N on enzymatic activities of ATPase and PK as potentials biochemical indicators of the levels of K+, Mg2+, and Ca2+ in the roots and leaves of green bean plants. The N was applied to the nutrient solution as NH4NO3 at the following rates: 1.5, 3.0, 6.0, 12.0, 18.0, and 24.0 mM of N. These results indicate that deficient conditions of N (N1 and N2) were characterized by the lowest accumulation of K+, Mg2+ and Ca2+ in both total and soluble forms, and also minimum activities of PK and ATPase induced by K+, Mg2+ and Ca2+, with respect to the activity of basal PK and ATPase; this could mean near optimum conditions for these cations. On the contrary, high-N treatments (N4, N5 and N6) were characterized by presenting decreasing concentrations of total and soluble K+, Mg2+ and Ca2+ in roots and leaves of green bean plants; however, the activities of PK and ATPase induced with K+, Mg2+ and Ca2+ were increased reaching their maximum activity with respect to basal PK and ATPase, both enzymes reflecting the level of cations in roots and leaves, hence being considered as good physiological bioindicators of these cations.Las actividades piruvato kinasa (PK) y ATPasa participan en la asimilación de nitrógeno (N), la cual es esencial para el crecimiento y desarrollo de las plantas. Estudios sobre cinéticas de estas enzimas revelan que sus actividades son dependientes de los cofactores K+, Ca2+ y Mg2+. Por lo tanto, el objetivo del presente trabajo fue determinar el efecto de diferentes dosis de N sobre las actividades de la ATPasa y PK como posibles bioindicadores de los niveles de K+, Mg2+ y Ca2+ en raíces y hojas de plantas de judía (Phaseolus vulgaris L. cv. Strike). Se aplicó N a la solución nutritiva como NH4NO3 en las siguientes dosis: N1=1,5 mM, N2=3,0 mM, N3=6,0 mM, N4=12,0 mM, N5=18,0 mM y N6=24,0 mM. Los resultados indican que bajo condiciones deficientes de N (N1 y N2), las plantas presentaron menor acumulación de K+, Mg2+ y Ca2+ en su forma total y soluble, así como mínimas actividades PK y ATPasa inducidas por K+, Mg2+ y Ca2+ respecto a la actividad PK y ATPasa basal; lo cual indica condiciones cercanas a las óptimas de estos cationes. Por el contrario, en los tratamientos elevados de N (N4, N5 y N6) las plantas presentaron concentraciones decrecientes de K+, Mg2+ y Ca2+ total y soluble tanto en raíces como en hojas; sin embargo, las actividades PK y ATPasa inducidas con K+, Mg2+ y Ca2+ se incrementaron alcanzando sus máximas actividades con respecto a la PK y ATPasa basal, lo que indica una mayor necesidad fisiológica de estos cationes en los tratamientos elevados de N. Finalmente, la actividad ATPasa basal y la inducida con K+, Mg2+ y Ca2+ se comportaron de forma similar a la actividad PK, lo que refleja el nivel de cationes en raíces y en hojas, por lo que se consideran buenos bioindicadores fisiológicos de estos cationes

Aprendizaje y consolidación de la asignatura de microbiología y parasitología medicas en la carrera de medicina.

Se aplicó un instrumento evaluativo de las esencialidades de la asignatura Microbiología y Parasitología Médicas (Agentes biológicos), en forma de encuesta anónima, a los estudiantes de Medicina de la Facultad "General Calixto García", quienes cursaron la asignatura en el 4to Semestre del curso 2003-2004, en varios Cortes: I antes de Propedéutica, al iniciar el 5to Semestre; II después de Medicina Interna, al finalizar el 6to Semestre; III después de Pediatría, al finalizar el 8vo Semestre y IV después de MGI II, en el Internado, para conocer si el futuro Médico General Básico (MGB), se había apropiado de esos conocimientos en la asignatura y valorar su consolidación en el Área Clínica. Los alumnos no demostraron el conocimiento esperado de los agentes causales de enfermedades infecciosas frecuentes en la población, no hubo retención de los objetivos instructivos de la asignatura y en el área clínica no se logró la consolidación de dichos objetivos.  Palabras clave: Docencia, evaluación, aprendizaje, asignatura

Impact of the selenisation temperature on the structural and optical properties of CZTSe absorbers

We present structural and optical spectroscopy studies of thin films of Cu2ZnSnSe4 (CZTSe) with strong copper deficiency deposited on Mo/Glass substrates and selenised at 450, 500 or 550 °C. Solar cells fabricated from these films demonstrated efficiencies up to 7.4% for selenisation at 500 °C. Structural analysis based on X-ray diffraction and Raman spectroscopy revealed the presence of SnSe2 in the film selenised at 450 °C but not detected in the films selenised at higher temperatures. A progressive decrease of the Sn and Se content was observed as the selenisation temperature increased. Photoluminescence excitation was used to determine the bandgaps at 4.2 K. Detailed measurements of the temperature and excitation intensity dependencies of the photoluminescence spectra allow the recombination mechanisms of the observed emission bands to be identified as band-to-impurity and band-to-band transitions, and their evolution with selenisation temperature changes to be analysed. The strongest band-to-band transition is recorded in the PL spectra of the film selenised at 500 °C and can be observed from 6 K to room temperature. The compositional and structural changes in the films and their influence on the optoelectronic properties of CZTSe and solar cells are discussed

Dynamics of dental evolution in ornithopod dinosaurs.

Ornithopods were key herbivorous dinosaurs in Mesozoic terrestrial ecosystems, with a variety of tooth morphologies. Several clades, especially the 'duck-billed' hadrosaurids, became hugely diverse and abundant almost worldwide. Yet their evolutionary dynamics have been disputed, particularly whether they diversified in response to events in plant evolution. Here we focus on their remarkable dietary adaptations, using tooth and jaw characters to examine changes in dental disparity and evolutionary rate. Ornithopods explored different areas of dental morphospace throughout their evolution, showing a long-term expansion. There were four major evolutionary rate increases, the first among basal iguanodontians in the Middle-Late Jurassic, and the three others among the Hadrosauridae, above and below the split of their two major clades, in the middle of the Late Cretaceous. These evolutionary bursts do not correspond to times of plant diversification, including the radiation of the flowering plants, and suggest that dental innovation rather than coevolution with major plant clades was a major driver in ornithopod evolution