Experimental Evidence and Clinical Implications of Pituitary Adenoma Stem Cells

Pituitary adenomas, accounting for 15% of diagnosed intracranial neoplasms, are usually benign and pharmacologically and surgically treatable; however, the critical location, mass effects and hormone hypersecretion sustain their significant morbidity. Approximately 35% of pituitary tumors show a less benign course since they are highly proliferative and invasive, poorly resectable, and likely recurring. The latest WHO classification of pituitary tumors includes pituitary transcription factor assessment to determine adenohypophysis cell lineages and accurate designation of adenomas, nevertheless little is known about molecular and cellular pathways which contribute to pituitary tumorigenesis. In malignant tumors the identification of cancer stem cells radically changed the concepts of both tumorigenesis and pharmacological approaches. Cancer stem cells are defined as a subset of undifferentiated transformed cells from which the bulk of cancer cells populating a tumor mass is generated. These cells are able to self-renew, promoting tumor progression and recurrence of malignant tumors, also conferring cytotoxic drug resistance. On the other hand, the existence of stem cells within benign tumors is still debated. The presence of adult stem cells in human and murine pituitaries where they sustain the high plasticity of hormone-producing cells, allowed the hypothesis that putative tumor stem cells might exist in pituitary adenomas, reinforcing the concept that the cancer stem cell model could also be applied to pituitary tumorigenesis. In the last few years, the isolation and phenotypic characterization of putative pituitary adenoma stem-like cells was performed using a wide and heterogeneous variety of experimental models and techniques, although the role of these cells in adenoma initiation and progression is still not completely definite. The assessment of possible pituitary adenoma-initiating cell population would be of extreme relevance to better understand pituitary tumor biology and to identify novel potential diagnostic markers and pharmacological targets. In this review, we summarize the most updated studies focused on the definition of pituitary adenoma stem cell phenotype and functional features, highlighting the biological processes and intracellular pathways potentially involved in driving tumor growth, relapse, and therapy resistance

Learning from the children : exploring preschool children's encounters with ICT at home

This paper is an account of our attempts to understand preschool children's experiences with information and communication technologies (ICT) at home. Using case study data, we focus on what we can learn from talking directly to the children that might otherwise have been overlooked and on describing and evaluating the methods we adopted to ensure that we maximised the children's contributions to the research. By paying attention to the children's perspectives we have learned that they are discriminating users of ICT who evaluate their own performances, know what gives them pleasure and who differentiate between operational competence and the substantive activities made possible by ICT

Searching for solar-like oscillations in pre-main sequence stars using APOLLO

In recent years, our understanding of solar-like oscillations from main sequence to red giant stars has improved dramatically thanks to pristine data collected from space telescopes. One of the remaining open questions focuses around the observational identification of solar-like oscillations in pre-main sequence stars. We aim to develop an improved method to search for solar-like oscillations in pre-main sequence stars and apply it to data collected by the Kepler K2 mission. Our software APOLLO includes a novel way to detect low signal-to-noise ratio solar like oscillations in the presence of a high background level. By calibrating our method using known solar-like oscillators from the main Kepler mission, we apply it to T Tauri stars observed by Kepler K2 and identify several candidate pre-main sequence solar-like oscillators. We find that our method is robust even when applied to time-series of observational lengths as short as those obtained with the TESS satellite in one sector. We identify EPIC 205375290 as a possible candidate for solar-like oscillations in a pre-main sequence star with $\nu_\mathrm{max} \simeq 242\,\mu$Hz. We also derive EPIC 205375290's fundamental parameters to be $T_\mathrm{eff}$ = 3670$\pm$180 K, log $g$ = 3.85$\pm$0.3, $v$sin$i$ = 8 $\pm$ 1 km s$^{-1}$, and about solar metallicity from a high-resolution spectrum obtained from the Keck archive.Comment: 14 pages, 13 figure

Limits on surface gravities of Kepler planet-candidate host stars from non-detection of solar-like oscillations

We present a novel method for estimating lower-limit surface gravities log g of Kepler targets whose data do not allow the detection of solar-like oscillations. The method is tested using an ensemble of solar-type stars observed in the context of the Kepler Asteroseismic Science Consortium. We then proceed to estimate lower-limit log g for a cohort of Kepler solar-type planet-candidate host stars with no detected oscillations. Limits on fundamental stellar properties, as provided by this work, are likely to be useful in the characterization of the corresponding candidate planetary systems. Furthermore, an important byproduct of the current work is the confirmation that amplitudes of solar-like oscillations are suppressed in stars with increased levels of surface magnetic activity.Comment: Accepted for publication in ApJ; 35 pages, 10 figures, 5 table

Human PrP90-231-induced cell death is associated with intracellular accumulation of insoluble and protease-resistant macroaggregates and lysosomal dysfunction

To define the mechanisms by which hPrP90-231 induces cell death, we analyzed its interaction with living cells and monitored its intracellular fate. Treatment of SH-SY5Y cells with fluorescein-5-isothiocyanate (FITC)-conjugated hPrP90-231 caused the accumulation of cytosolic aggregates of the prion protein fragment that increased in number and size in a time-dependent manner. The formation of large intracellular hPrP90-231 aggregates correlated with the activation of apoptosis. hPrP90-231 aggregates occurred within lysotracker-positive vesicles and induced the formation of activated cathepsin D (CD), indicating that hPrP90-231 is partitioned into the endosomal–lysosomal system structures, activating the proteolytic machinery. Remarkably, the inhibition of CD activity significantly reduced hPrP-90-231-dependent apoptosis. Internalized hPrP90-231 forms detergent-insoluble and SDS-stable aggregates, displaying partial resistance to proteolysis. By confocal microscopy analysis of lucifer yellow (LY) intracellular partition, we show that hPrP90-231 accumulation induces lysosome destabilization and loss of lysosomal membrane impermeability. In fact, although control cells evidenced a vesicular pattern of LY fluorescence (index of healthy lysosomes), hPrP90-231-treated cells showed diffuse cytosolic fluorescence, indicating LY diffusion through damaged lysosomes. In conclusion, these data indicate that exogenously added hPrP90-231 forms intralysosomal deposits having features of insoluble, protease-resistant aggregates and could trigger a lysosome-mediated apoptosis by inducing lysosome membrane permeabilization, followed by the release of hydrolytic enzymes

The biosocial event : responding to innovation in the life sciences

Innovation in the life sciences calls for reflection on how sociologies separate and relate life processes and social processes. To this end we introduce the concept of the ‘biosocial event’. Some life processes and social processes have more mutual relevance than others. Some of these relationships are more negotiable than others. We show that levels of relevance and negotiability are not static but can change within existing relationships. Such changes, or biosocial events, lie at the heart of much unplanned biosocial novelty and much deliberate innovation. We illustrate and explore the concept through two examples – meningitis infection and epidemic, and the use of sonic ‘teen deterrents’ in urban settings. We then consider its value in developing sociological practice oriented to critically constructive engagement with innovation in the life sciences

'The terrible twos': Gaining control in the nursery?

'The terrible twos' are often described as a time of 'gaining control', usually thought of as adults asserting control over children, who learn to control themselves. However, toddlerhood is as much about children learning to take control for themselves. This paper is an attempt to detail something of the social geography in the toddler room of a Scottish nursery, considering both styles of adult control and the ways in which toddlers attempt to appropriate and reconfigure space and time for themselves. That is, the ways in which space and time are negotiated in the course of day-to-day nursery life

Asteroseismic fundamental properties of solar-type stars observed by the NASA Kepler Mission

We use asteroseismic data obtained by the NASA Kepler Mission to estimate the fundamental properties of more than 500 main-sequence and sub-giant stars. Data obtained during the first 10 months of Kepler science operations were used for this work, when these solar-type targets were observed for one month each in a survey mode. Stellar properties have been estimated using two global asteroseismic parameters and complementary photometric and spectroscopic data. Homogeneous sets of effective temperatures were available for the entire ensemble from complementary photometry; spectroscopic estimates of T_eff and [Fe/H] were available from a homogeneous analysis of ground-based data on a subset of 87 stars. [Abbreviated version... see paper for full abstract.]Comment: Accepted for publication in ApJS; 90 pages, 22 figures, 6 tables. Units on rho in tables now listed correctly as rho(Sun

Finding a voice: A figured worlds approach to theorising young children's identities

This article explores some of the ways in which children’s ethnic identities have been conceptualised by sociocultural and critical race theory and the potential of the ‘figured worlds’ literature in helping to theorise the responses of young children to the cultural and educational worlds they encounter. Using some vignettes drawn from the author’s ethnographic study of the ethnic identities of a group of 3- and 4-year-old White British and British Pakistani children in a kindergarten in the north of England, the article explores the potential of a figured worlds analysis in understanding how the children respond to some of the experiences of the kindergarten and in understanding how they seek to make sense of their identities. The article concludes that while structural and cultural factors shaped the ways in which the children engaged or did not engage in the social and educational practices of the kindergarten and played a very significant part in how they viewed themselves and viewed others, the children were not silent observers of what the world offered or did not offer them. A dialogic self was evident that authored and tried to make sense of the world, but, in so doing, designated identities meant that only particular figured worlds were available to children for much of the time. It is argued that what a figured worlds reading offers is a means of seeking to uncover and theorise the complex ways in which young children experience and perform their identities and respond to the social and educational practices in particular contexts. This is seen as having value in providing a framework for early childhood academics and educators to work together to support children in exploring alternative figured identities that challenge, alleviate and transform the constraints that positional identities often seem to impose on them