Stem and progenitor cell division kinetics during postnatal mouse mammary gland development.

The cycling properties of mammary stem and progenitor cells is not well understood. To determine the division properties of these cells, we administered synthetic nucleosides for varying periods of time to mice at different stages of postnatal development and monitored the rate of uptake of these nucleosides in the different mammary cell compartments. Here we show that most cell division in the adult virgin gland is restricted to the oestrogen receptor-expressing luminal cell lineage. Our data also demonstrate that the oestrogen receptor-expressing, milk and basal cell subpopulations have telomere lengths and cell division kinetics that are not compatible with these cells being hierarchically organized; instead, our data indicate that in the adult homeostatic gland, each cell type is largely maintained by its own restricted progenitors. We also observe that transplantable stem cells are largely quiescent during oestrus, but are cycling during dioestrus when progesterone levels are high.We thank the members of Stingl lab, Doug Winton, Jason Carroll, Robert Clarke, Phil Jones and Hamid Raza Ali for scientific discussions. We thank the core facilities at the Cancer Research UK-CI for enabling experiments. In particular, Loic Tauzin, Nina Lane and Mateuz Strzelecki for assistance with cell sorting; the Biological Resources Unit for animal husbandry; and Histopathology staff, in particular Leigh-Anne McDuffus and Cara Walters. J. Stingl’s laboratory acknowledges the support of The University of Cambridge, Cancer Research UK (core grant number C14303/A17197) and Hutchison Whampoa Limited. M.A. Blasco’s laboratory is funded by the Spanish Ministry of Economy and Competitiveness Project SAF2013-45111RETOS, the European Union FP7 Project EUROBATS, the European Research Council (ERC) Project TEL STEM CELL (GA#232854), the Regional Government of Madrid project 2+2 ReCaRe, the AXA Research Fund and the Fundación Botín.This is the final version of the article. It was first available from Nature via http://dx.doi.org/10.1038/ncomms948

Evaluation of the iridocorneal angle with accommodation using optical coherence tomography.

The changes in the iridocorneal angle structure during accommodation are assessed by means of anterior segment optical coherence tomography. Thirteen right eyes were included in the study. The device used for the measurement was the Visante®omni system. The stimuli were set up at different vergences (0.0 D, -1.5 D, and -3.0 D). The angle opening distance 500 and 750, the trabecular iris space area 500 and 750, and the scleral spur angle parameters were assessed at the nasal and temporal regions. The results in the iridotrabecular angle comparing the three accommodative states of the eye did not yield any statistically significant difference at nasal or temporal angle sections. In light of our results and in the conditions of our study, the structures of the iridocorneal angle are not significantly changed with accommodation

Passivity Breakdown of Titanium in LiBr solutions

The passive behavior of titanium and its susceptibility to undergo localized attack in different LiBr solutions at 25 degrees C have been investigated using different electrochemical techniques: potentiodynamic polarization curves, potentiostatic passivation tests, EIS measurements and Mott-Schottky analysis. In low and moderately concentrated LiBr solutions, the breakdown potential E-b decreased with increasing bromide concentrations, while in highly concentrated LiBr solutions, E-b increased with increasing LiBr concentration. In the most concentrated LiBr solution (11.42M) Ti did not undergo passivity breakdown even at 9 V-Ag/AgCl. This observation can be explained by a a decrease in the activity of water in highly concentrated LiBr solutions. (C) 2013 The Electrochemical Society.We wish express our gratitude to the Ministerio de Ciencia e Innovacion (Project CTQ2009-07518), and to Dr. M. Asuncion Jaime. for her translation assistance.Fernández Domene, RM.; Blasco-Tamarit, E.; García-García, D.; García Antón, J. (2014). Passivity Breakdown of Titanium in LiBr solutions. Journal of The Electrochemical Society. 161(1):25-35. https://doi.org/10.1149/2.035401jesS25351611Been J. Grauman J. S. , in: Uhlig's Corrosion Handbook, 2nd ed., Winston Revie R. (ed.), 863-885, Wiley Interscience, New York (2000).Blasco-Tamarit, E., Igual-Muñoz, A., García Antón, J., & García-García, D. (2007). Corrosion behaviour and galvanic coupling of titanium and welded titanium in LiBr solutions. Corrosion Science, 49(3), 1000-1026. doi:10.1016/j.corsci.2006.07.007Huang, Y. Z., & Blackwood, D. J. (2005). Characterisation of titanium oxide film grown in 0.9% NaCl at different sweep rates. Electrochimica Acta, 51(6), 1099-1107. doi:10.1016/j.electacta.2005.05.051Pan, J., Thierry, D., & Leygraf, C. (1996). 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Crowding Promotes the Switch from Hairpin to Pseudoknot Conformation in Human Telomerase RNA

Formation of a pseudoknot in the conserved RNA core domain in the ribonucleoprotein human telomerase is required for function. In vitro experiments show that the pseudoknot (PK) is in equilibrium with an extended hairpin (HP) structure. We use molecular simulations of a coarse-grained model, which reproduces most of the salient features of the experimental melting profiles of PK and HP, to show that crowding enhances the stability of PK relative to HP in the wild type and in a mutant associated with dyskeratosis congenita. In monodisperse suspensions, small crowding particles increase the stability of compact structures to a greater extent than larger crowders. If the sizes of crowders in a binary mixture are smaller than the unfolded RNA, the increase in melting temperature due to the two components is additive. In a ternary mixture of crowders that are larger than the unfolded RNA, which mimics the composition of ribosome, large enzyme complexes and proteins in E. coli, the marginal increase in stability is entirely determined by the smallest component. We predict that crowding can restore partially telomerase activity in mutants, which dramatically decrease the PK stability.Comment: File "JACS_MAIN_archive_PDF_from_DOC.pdf" (PDF created from DOC) contains the main text of the paper File JACS_SI_archive.tex + 7 figures are the supplementary inf

Changes in Social and Clinical Determinants of COVID-19 Outcomes Achieved by the Vaccination Program: A Nationwide Cohort Study

Background: The objective of this study was to assess changes in social and clinical determinants of COVID-19 outcomes associated with the first year of COVID-19 vaccination rollout in the Basque population. Methods: A retrospective study was performed using the complete database of the Basque Health Service (n = 2,343,858). We analyzed data on age, sex, socioeconomic status, the Charlson comorbidity index (CCI), hospitalization and intensive care unit (ICU) admission, and COVID-19 infection by Cox regression models and Kaplan–Meier curves. Results: Women had a higher hazard ratio (HR) of infection (1.1) and a much lower rate of hospitalization (0.7). With older age, the risk of infection fell, but the risks of hospitalization and ICU admission increased. The higher the CCI, the higher the risks of infection and hospitalization. The risk of infection was higher in high-income individuals in all periods (HR = 1.2–1.4) while their risk of hospitalization was lower in the post-vaccination period (HR = 0.451). Conclusion: Despite the lifting of many control measures during the second half of 2021, restoring human mobility patterns, the situation could not be defined as syndemic, clinical determinants seeming to have more influence than social ones on COVID-19 outcomes, both before and after vaccination program implementation

The effect of mixed vaccination rollout strategy: A modelling study

Vaccines have measurable efficacy obtained first from vaccine trials. However, vaccine efficacy (VE) is not a static measure and long-term population studies are needed to evaluate its performance and impact. COVID-19 vaccines have been developed in record time and the currently licensed vaccines are extremely effective against severe disease with higher VE after the full immunization schedule. To assess the impact of the initial phase of the COVID-19 vaccination rollout programmes, we used an extended Susceptible - Hospitalized - Asymptomatic/mild - Recovered ($SHAR$) model. Vaccination models were proposed to evaluate different vaccine types: vaccine type 1 which protects against severe disease only but fails to block disease transmission, and vaccine type 2 which protects against both severe disease and infection. VE was assumed as reported by the vaccine trials incorporating the difference in efficacy between one and two doses of vaccine administration. We described the performance of the vaccine in reducing hospitalizations during a momentary scenario in the Basque Country, Spain. With a population in a mixed vaccination setting, our results have shown that reductions in hospitalized COVID-19 cases were observed five months after the vaccination rollout started, from May to June 2021. Specifically in June, a good agreement between modelling simulation and empirical data was well pronounced.BERC 2022-2025 Marie Curie No~792494 Severo Ochoa CEX2021-001142-S/ MICIN / AEI / 10.13039/501100011033 EITB Marathon 2021 call BIO21/COV/00

Photoemission study of the metal-insulator transition in VO_2/TiO_2(001) : Evidence for strong electron-electron and electron-phonon interaction

We have made a detailed temperature-dependent photoemission study of VO_2/TiO_2(001) thin films, which show a metal-insulator transition at \sim 300 K. Clean surfaces were obtained by annealing the films in an oxygen atmosphere. Spectral weight transfer between the coherent and incoherent parts accompanying the metal-insulator transition was clearly observed. We also observed a hysteretic behavior of the spectra for heating-cooling cycles. We have derived the ``bulk'' spectrum of the metallic phase and found that it has a strong incoherent part. The width of the coherent part is comparable to that given by band-structure calculation in spite of its reduced spectral weight, indicating that the momentum dependence of the self-energy is significant. This is attributed to by ferromagnetic fluctuation arising from Hund's rule coupling between different d orbitals as originally proposed by Zylbersztejn and Mott. In the insulating phase, the width of the V 3d band shows strong temperature dependence. We attribute this to electron-phonon interaction and have reproduced it using the independent boson model with a very large coupling constant.Comment: 7 pages, 7 figures, submitted to Phys. Rev.

Comment on "X-ray resonant scattering studies of orbital and charge ordering in Pr1-xCaxMnO3"

In a recent published paper [Phys. Rev. B 64, 195133 (2001)], Zimmermann et al. present a systematic x-ray scattering study of charge and orbital ordering phenomena in the Pr1-xCaxMnO3 series with x= 0.25, 0.4 and 0.5. They propose that for Ca concentrations x=0.4 and 0.5, the appearance of (0, k+1/2, 0) reflections are originated by the orbital ordering of the eg electrons in the a-b plane while the (0, 2k+1, 0) reflections are due to the charge ordering among the Mn3+ and Mn4+ ions. Moreover, for small Ca concentrations (x<0.3), the orbital ordering is only considered and it occurs at (0, k, 0) reflections. A rigorous analysis of all these resonance reflections will show the inadequacy of the charge-orbital model proposed to explain the experimental results. In addition, this charge-orbital model is highly inconsistent with the electronic balance. On the contrary, these reflections can be easily understood as arising from the anisotropy of charge distribution induced by the presence of local distortions, i.e. due to a structural phase transition.Comment: 10 pages, 2 figures.To be published Phys. Rev.

A hard X- ray probe to study doping-dependent electron redistribution and strong covalency in La_{1-x}Sr_{1+x}MnO_4

The effect of doping on the electronic structure at the Mn sites in the La_{1-x}Sr_{1+x}MnO_4 series (x=0, 0.3 and 0.5) was studied by means of non-resonant hard X- ray emission spectroscopy (XES). We observe a linear dichroism in the Mn K-beta main lines (3p to 1s transitions) that is strongest for x=0 and decreases with increasing x to 0.5. The Mn K-beta main lines in the poly-crystalline samples change considerably less upon increasing the hole doping (substitution of La by Sr) than it would be expected based on the change of formal valence. From this we conclude that the charge and spin density at the Mn sites are only little affected by doping. This implies that holes injected in the La_{1-x}Sr_{1+x}MnO_4 series mainly result in a decrease of charge density on the oxygen atoms, i.e. oxygen takes part in the charge balancing. These findings are supported by many-body cluster calculations

Local structural changes in paramagnetic and charge ordered phases of Sm0.2Pr0.3Sr0.5MnO3: An EXAFS Study

Sm{0.5-x}Pr{x}Sr{0.5}MnO{3} exhibits variety of ground states as x is varied from 0 to 0.5. At an intermediate doping of x = 0.3 a charge-ordered CE type antiferromagnetic insulating (AFI) ground state is seen. The transition to this ground state is from a paramagnetic insulating (PMI) phase through a ferromagnetic metallic phase (FMM). Local structures in PMI and AFI phases of x = 0.3 sample have been investigated using Pr K-edge and Sm K-edge Extended X-ray Absorption Fine Structure (EXAFS). It can be seen that the tilting and rotation of the MnO6 octahedra about the b-axis are responsible for the charge ordered CE-type antiferromagnetic ground state at low temperatures. In addition a shift in the position of the rare earth ion along the c-axis has to be considered to account for observed distribution of bond distances around the rare earth ion