2,560 research outputs found
Transient activaton of β-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours
When β-catenin signalling is disturbed from mid-gestation onwards lineage commitment is profoundly altered in postnatal mouse epidermis. We have investigated whether adult epidermis has the capacity for β-catenin-induced lineage conversion without prior embryonic priming. We fused N-terminally truncated, stabilised β-catenin to the ligand-binding domain of a mutant oestrogen receptor (ΔNβ -cateninER). ΔNβ-cateninER was expressed in the epidermis of transgenic mice under the control of the keratin 14 promoter and β -catenin activity was induced in adult epidermis by topical application of 4-hydroxytamoxifen (4OHT). Within 7 days of daily 4OHT treatment resting hair follicles were recruited into the hair growth cycle and epithelial outgrowths formed from existing hair follicles and from interfollicular epidermis. The outgrowths expressed Sonic hedgehog, Patched and markers of hair follicle differentiation, indicative of de novo follicle formation. The interfollicular epidermal differentiation program was largely unaffected but after an initial wave of sebaceous gland duplication sebocyte differentiation was inhibited. A single application of 4OHT was as effective as repeated doses in inducing new follicles and growth of existing follicles. Treatment of epidermis with 4OHT for 21 days resulted in conversion of hair follicles to benign tumours resembling trichofolliculomas. The tumours were dependent on continuous activation of β-catenin and by 28 days after removal of the drug they had largely regressed. We conclude that interfollicular epidermis and sebaceous glands retain the ability to be reprogrammed in adult life and that continuous β-catenin signalling is required to maintain hair follicle tumours.Peer reviewedFinal Published versio
Automated Identification and Measurement of Haematopoietic Stem Cells in 3D Intravital Microscopy Data
Image analysis and quantification of Haematopoietic stem cells (HSCs) position within their surrounding microenvironment in the bone marrow is a fast growing area of research, as it holds the key to understanding the dynamics of HSC-niche interactions and their multiple implications in normal tissue development and in response to various stress events. However, this area of research is very challenging due to the complex cellular structure of such images. Therefore, automated image analysis tools are required to simplify the biological interpretation of 3D HSC microenvironment images. In this chapter, we describe how 3D intravital microscopy data can be visualised and analysed using a computational method that allows the automated quantification of HSC position relative to surrounding niche components
In vivo 4-dimensional tracking of hematopoietic stem and progenitor cells in adult mouse calvarial bone marrow
Through a delicate balance between quiescence and proliferation, self renewal and production of differentiated progeny, hematopoietic stem cells (HSCs) maintain the turnover of all mature blood cell lineages. The coordination of the complex signals leading to specific HSC fates relies upon the interaction between HSCs and the intricate bone marrow microenvironment, which is still poorly understood[1-2]. We describe how by combining a newly developed specimen holder for stable animal positioning with multi-step confocal and two-photon in vivo imaging techniques, it is possible to obtain high-resolution 3D stacks containing HSPCs and their surrounding niches and to monitor them over time through multi-point time-lapse imaging. High definition imaging allows detecting ex vivo labeled hematopoietic stem and progenitor cells (HSPCs) residing within the bone marrow. Moreover, multi-point time-lapse 3D imaging, obtained with faster acquisition settings, provides accurate information about HSPC movement and the reciprocal interactions between HSPCs and stroma cells. Tracking of HSPCs in relation to GFP positive osteoblastic cells is shown as an exemplary application of this method. This technique can be utilized to track any appropriately labeled hematopoietic or stromal cell of interest within the mouse calvarium bone marrow space
The interplay of leukemia cells and the bone marrow microenvironment
The interplay of cancer cells and surrounding stroma is critical in disease progression. This is particularly evident in hematological malignancies that infiltrate the bone marrow and peripheral lymphoid organs. Despite clear evidence for the existence of these interactions, the precise repercussions on the growth of leukemic cells are poorly understood. Recent development of novel imaging technology and preclinical disease models have advanced our comprehension of leukemia-microenvironment crosstalk and have potential implications for development of novel treatment options
La comunicaciĂłn no verbal de los candidatos Daniel Scioli y Mauricio Macri en el espacio de debate
Durante la campaña presidencial del 2015 en Argentina, me detuve a observar cómo se daban
a conocer los candidatos, quĂ© mensajes pretendĂan transmitir, quĂ© estrategias implementaban,
cómo comunicaban con su cuerpo, con sus movimientos, posturas, miradas, vestimenta y qué
significado transmitĂan sus gestos. El objetivo de este trabajo es analizar cĂłmo impactĂł la
comunicación no verbal a la hora de formar una opinión sobre los candidatos. Opté en
focalizarme en los dos candidatos que participaron en el debate organizado por la ONG
Argentina Debate, que tuvo lugar el 15 de noviembre de 2015, en el SalĂłn de Actos de la
Facultad de Derecho de la Universidad de Buenos Aires, ubicada en Av. Pres. Figueroa
Acorta 2263, Ciudad AutĂłnoma de Buenos Aires.
Ese dĂa, a las 21 horas se enfrentaron Daniel Scioli, candidato del Frente para la Victoria y
Mauricio Macri, de la alianza Cambiemos.
He aquà un análisis sobre cómo se manifestó la comunicación no verbal en ambos candidatos,
cuya aspiraciĂłn era ocupar el mando Presidencial.Fil: Lo Celso, Carolina. Universidad Nacional de Rosario. Facultad de Ciencia PolĂtica y Relaciones Internacionales. Escuela de ComunicaciĂłn Social; Argentin
Liquid Structure Scenario of the Archetypal Supramolecular Deep Eutectic Solvent: Heptakis(2,6-di-O-methyl)-β-cyclodextrin/levulinic Acid
The concept of supramolecular solvents has been
recently introduced, and the extended liquid-state window
accessible for mixtures of functionalized cyclodextrins (CDs)
with hydrogen bond (HB) donor species, e.g., levulinic acid, led to
the debut of supramolecular deep eutectic solvents (SUPRA-DES).
These solvents retain CD’s inclusion ability and complement it
with enhanced solvation effectiveness due to an extended HB
network. However, so far, these promising features were not
rationalized in terms of a microscopic description, thus hindering a
more complete capitalization. This is the first joint experimental
and computational study on the archetypal SUPRA-DES: heptakis-
(2,6-di-O-methyl)-β-CD/levulinic acid (1:27). We used X-ray
scattering to probe CD’s aggregation level and molecular dynamics
simulation to determine the nature of interactions between SUPRA-DES components. We discover that CDs are homogeneously distributed in bulk and that HB interactions, together with the electrostatic ones, play a major role in determining mutual interaction between components. However, dispersive forces act in synergy with HB to accomplish a fundamental task in hindering hydrophobic interactions between neighbor CDs and maintaining the system homogeneity. The mechanism of mutual solvation of CD and levulinic acid is fully described, providing fundamental indications on how to extend the spectrum of SUPRA-DES combinations. Overall, this study provides the key to interpreting structural organization and solvation tunability in SUPRA-DES to extend the range of sustainable applications for these new, unique solvents
Applied neutron tomography in modern archaeology
The use of neutron tomography for archaeometric purposes is quite a new technique. The property of neutron to transmit easily large, dense samples is of great importance in modern archaeology. The three-dimensional visualisation of the inner structure of samples of archaeological interest helps to make suggestions about the technological process of manufacturing or reveals information about the origins of
delivering of noble materials used in ancient masterpieces. Another application field in modern archaeology is the
non-destructive inspection of the quality of specimen
conservation where the neutron tomography allows visualization of impregnation solutions in wood or metal matrices. The high sensibility of neutrons to hydrogen
makes it possible to detect organic remains in fossils. All of these advantages make the neutron tomography a unique technique for non-destructive investigation in
archaeological sciences
Targeting adhesion to the vascular niche to improve therapy for acute myeloid leukemia
Niche hijack by malignant cells is considered to be a prominent cause of disease relapse. Barbier and colleagues uncover (E)-selectin as a novel mediator of malignant cell survival and regeneration which, upon blockade, has the potential to significantly improve therapeutic outcomes
Fingerprinting white marbles of archaeometric interest by means of combined SANS and USANS
We have performed a series of USANS and SANS measurements on
a selected group of marble samples characterized by similar chemical composition but wide range of known metamorphic conditions. With these samples we start the building up of a data base in an attempt to correlate metamorphism and mesoscopic structure of white marbles. Experimental data have been analysed in terms of a hierarchical model. The present data highlight the importance of the structure at
meso scale in identifying the provenance of the marble samples. A remarkable simple relation between the model parameters and the metamorphic degree has been found. This curve might represent a master curve to allow fingerprinting of white marbles. Also, two coloured marbles from Villa Adriana (Tivoli, Italy) have been investigated
by means of the same techniques. Results obtained follow the general trend found for the white marbles
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