Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells

In response to physiological demand, the pituitary gland generates new hormonesecreting cells from committed progenitor cells throughout life. It remains unclear to what extent pituitary stem cells (PSCs), which uniquely express SOX2, contribute to pituitary growth and renewal. Moreover, neither the signals that drive proliferation nor their sources have been elucidated. We have used genetic approaches in the mouse, showing that the WNT pathway is essential for proliferation of all lineages in the gland. We reveal that SOX2+ stem cells are a key source of WNT ligands. By blocking secretion of WNTs from SOX2+ PSCs in vivo, we demonstrate that proliferation of neighbouring committed progenitor cells declines, demonstrating that progenitor multiplication depends on the paracrine WNT secretion from SOX2+ PSCs. Our results indicate that stem cells can hold additional roles in tissue expansion and homeostasis, acting as paracrine signalling centres to coordinate the proliferation of neighbouring cells

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Expression Analysis of the Hippo Cascade Indicates a Role in Pituitary Stem Cell Development

The pituitary gland is a primary endocrine organ that controls major physiological processes. Abnormal development or homeostatic disruptions can lead to human disorders such as hypopituitarism or tumours. Multiple signalling pathways, including WNT, BMP, FGF and SHH regulate pituitary development but the role of the Hippo-YAP1/TAZ cascade is currently unknown. In multiple tissues, the Hippo kinase cascade underlies neoplasias; it influences organ size through the regulation of proliferation and apoptosis, and has roles in determining stem cell potential. We have used a sensitive mRNA in situ hybridisation method (RNAscope) to determine the expression patterns of the Hippo pathway components during mouse pituitary development. We have also carried out immunolocalisation studies to determine when YAP1 and TAZ, the transcriptional effectors of the Hippo pathway, are active. We find that YAP1/TAZ are active in the stem/progenitor cell population throughout development and at postnatal stages, consistent with their role in promoting the stem cell state. Our results demonstrate for the first time the collective expression of major components of the Hippo pathway during normal embryonic and postnatal development of the pituitary gland

Adult Pituitary Data1

GFP fluorescence measured from single cells in adult pituitary tissue and subsequent modelling of transcription activity using a stochastic switch model

Contemporary Mongolian folklore.

in english The aim of this work is to acquaint the reader with research on contemporary legends in Mongolia. This topic has not been explored among folklorists enought yet. I focused first on the general characteristics of contemporary legends, its dissemination, typology and history of research. I further elaborated, using literature and my own field research, the actual situation in Mongolia. Collected contemporary legends are accompanied by folkloric commentary. Attention is also paid to the city of Ulan Bator as a place where most of the tales were collected

E18_5 Pituitary Data1

GFP fluorescence measured from single cells in embryonic day18.5 pituitary tissue and subsequent modelling of transcription activity using a stochastic switch model

The handwritten dictionary of lithuanian language from 1st half of 19th century from the Library of the National Museum

The intention of this work lays on processing, exploration and press-preparation (at least partially) of the handwritten relic, deposited in the Library of the National Museum. This archival document is possible to date to the first half of 19th century and connect it with lithuanistic legacy of František Ladislav Čelakovský. To understand the genesis of this lexicographic project is necessary to compare this dictionary with other work - Wýpisky o gazyku litewském. 1833 (sign.: IX E 4). The defined purpose expects to solve these tasks: 1. To validate or refute authorship of F. L. Čelakovský. Incorporate this handwritten relic to the context of lexicographic and baltoslavic interests of the author. 2. To explore the disposition of Lithuanian dictionary: main intention, role of the dictionary, scope of lexicon, thematic range. 3. To compare notification of the first half of 19th century to knowledge of contemporary lithuanistic. This work continues in modest previous exploration and wants to make a contribution to release this relic to the scientific awareness

Adult Pituitary Data3

GFP fluorescence measured from single cells in adult pituitary tissue and subsequent modelling of transcription activity using a stochastic switch model

Adult Pituitary_Cx_AGA_Data2

GFP fluorescence measured from single cells in adult pituitary tissue treated with 18alpha-glycyrrhetinic acid (20uM) for 2hrs prior to confocal imaging. Compare to Adult Pituitary Data3