bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and predictors of cancer specific distress in men with a family history of prostate cancer
Authors: McDowell M. E. , Occhipinti S. , Gardiner R. A. , Chambers S. K. 
Published: May 2013

AbstractObjectiveTo examine prevalence and predictors of cancer‐specific distress in undiagnosed men with and without a family history of prostate cancer, and to examine the contribution of perceptions of an affected relative's cancer experience on the distress of unaffected male relatives.MethodsMen with a first degree relative with prostate cancer (n = 207) and men without a family history (n = 239) from Australia completed a Computer Assisted Telephone Interview. Participants completed the Prostate Cancer Anxiety Subscale of the Memorial Anxiety Scale for Prostate Cancer, measures of perceived risk, and socio‐demographic information. Men with a family history provided details about their family history (number of relatives diagnosed with and dead from prostate cancer, relationship to affected relative, months since diagnosis) and reported their perceptions of their affected relative's prostate cancer experience including perceptions of threat related to the relative's diagnosis and perceived treatment phase and prognosis.ResultsCancer‐specific distress was low for all men and there was no significant difference in the distress experienced by men with and without a family history. Regression analyses showed that for all men, cancer‐specific distress increased with urinary symptoms and decreased in those with higher education and in older participants. For men with a family history, having a relative who died from prostate cancer and perceiving greater threat from a relative's diagnosis was associated with greater cancer‐specific distress.ConclusionsInterventions would benefit from examining appraisals of familial risk and examining prospective assessments of distress in the unaffected male relatives of men with prostate cancer over the course of the cancer trajectory. Copyright © 2013 John Wiley & Sons, Ltd.
Onwards or Homewards? Complex Graduate Migration Pathways, Well‐being, and the ‘Parental Safety Net’
Authors: Sage Joanna , Evandrou Maria , Falkingham Jane 
Published: May 2013

ABSTRACTPre‐existing literatures on post‐student migration have mainly focused on inter‐regional flows of young educated migrants, the attendant redistribution of human capital around the UK, and the impact on local and regional economies. This paper argues that the parochial focus on labour‐motivated graduate migration (usually to first employment), and the absence of data enabling individual migration histories to be traced longitudinally across the post‐student phase of the lifecourse, has masked the complexity of the patterns and processes of migration in this social group. Drawing upon recently collected primary data from a retrospective survey of the migration histories of a cohort of students who left the University of Southampton (UK) between 2001 and 2007, this paper reveals that post‐student migration trajectories are complex and precarious across the 5‐year period after leaving university. During this prolonged period of instability, the parental home (and parental support more generally) provides a crucial safety net. This begs questions about the impacts of post‐student transitions to financial and residential independence on the resources and intergenerational care exchange frameworks of contemporary mid‐life parents (terms such as ‘sandwich generation’ and ‘pivot generation’ refer to the multiple family roles and responsibilities of mid‐life parents who are caught between meeting the needs of their adult children and their ageing parents). It is suggested that the well‐being agenda in migration studies is helpful for refocusing the lens of enquiry on the impacts of return migration to the parental home on graduate migrants, their families, and the potential trade‐offs that might occur between generations. Copyright © 2013 John Wiley & Sons, Ltd.
What Makes New Grandparents Satisfied with Their Lives?
Authors: Ben Shlomo Shirley 
Published: May 2013

AbstractThe study examined the contribution of sociodemographic characteristics, perceived stress, and cognitive appraisals of grandparenthood to life satisfaction among new grandparents. The theoretical framework was Lazarus and Folkman's stress and coping model and the positive psychology approach. The sample consisted of 246 Israeli grandparents (aged 42–72 years) who completed a set of questionnaires 3–24 months after the birth of their first grandchild. The results showed that higher levels of life satisfaction were associated with younger age of grandparents, higher levels of physical health and economic status, and lower grandparent distress. Moreover, maternal grandparents reported higher appraisals of challenge and threat than did paternal grandparents, and grandfathers reported a higher perception of dysfunctional interaction with the grandchild than did grandmothers. Most importantly, the participants' cognitive appraisals were found to moderate the perceptions of stress generated by the birth of a first grandchild. The study highlights the need for preventive interventions aimed at promoting factors that can empower new grandparents who have difficulty coping with their new role. Copyright © 2013 John Wiley & Sons, Ltd.
Brief report: Musashi1-eGFP mice, a new tool for differential isolation of the intestinal stem cell populations
Authors: Maria Cambuli Francesca , Rezza Amélie , Nadjar Julien , Plateroti Michelina 
Published: May 2013

Abstract
The intestinal epithelium self-renews rapidly and continuously throughout life, due to the presence of crypt stem cells. Two pools of these cells have been identified in the small intestine, which differ in position (“+4” or the bottom of the crypts), expression of specific markers (Bmi1/mTert or Lgr5/Ascl2), and cell cycle characteristics. Interestingly, the RNA-binding protein Musashi1 is expressed in both populations and therefore a potential marker for both stem cell types. In order to locate, isolate, and study Musashi1-expressing cells within the intestinal epithelium, we generated transgenic mice expressing GFP fluorescent protein under the control of a 7-kb Msi1 promoter. The expression pattern of GFP in the intestinal crypts of both small and large intestines completely overlapped that of Musashi1, validating our model. By using fluorescence-activated cell sorting, cellular, and molecular analyses, we showed that GFP-positive Msi1-expressing cells are divided into two major pools corresponding to the Lgr5- and mTert-expressing stem cells. Interestingly, monitoring the cell cycle activity of the two sorted populations reveals that they are both actively cycling, although differences in cell cycle length were confirmed. Altogether, our new reporter mouse model based upon Musashi1 expression is a useful tool to isolate and study stem cells of the intestinal epithelium. Moreover, these mice uniquely enable the concomitant study of two pools of intestinal stem cells within the same animal model.
Somatic loss of p53 leads to stem/progenitor cell amplification in both mammary epithelial compartments, basal and luminal
Authors: Chiche Aurélie , Moumen Mejdi , Petit Valérie , Jonkers Jos , Medina Daniel , Deugnier Marie-Ange , Faraldo Marisa M. , Glukhova Marina A. 
Published: May 2013

Abstract
Mammary epithelium comprises a layer of luminal cells and a basal myoepithelial cell layer. Both mammary epithelial compartments, basal and luminal, contain stem and progenitor cells, but only basal cells are capable of gland regeneration upon transplantation. Aberrant expansion of stem/progenitor cell populations is considered to contribute to breast tumorigenesis. Germline deletions of p53 in humans and mice confer a predisposition to tumors, and stem cell frequency is abnormally high in the mammary epithelium of p53-deficient mice. However, it is unknown whether stem/progenitor cell amplification occurs in both, basal and luminal cell populations in p53-deficient mammary tissue. We used a conditional gene deletion approach to study the role of p53 in stem/progenitor cells residing in the mammary luminal and basal layers. Using two- and three-dimensional cell culture assays, we showed that p53 loss led to the expansion of clonogenic stem/progenitor cells in both mammary epithelial cell layers. Moreover, following p53 deletion, luminal and basal stem/progenitor cells acquired a capacity for unlimited propagation in mammosphere culture. Furthermore, limiting dilution and serial transplantation assays revealed amplification and enhanced self-renewal in the basal regenerating cell population of p53-deficient mammary epithelium. Our data suggest that the increase in stem/progenitor cell activity may be, at least, partially mediated by the Notch pathway. Taken together, these results strongly indicate that p53 restricts the propagation and self-renewal of stem/progenitor cells in both layers of the mammary epithelium providing further insight into the impact of p53 loss in breast cancerogenesis.
High throughput screening for inhibitors of REST in neural derivatives of human embryonic stem cells reveals a chemical compound that promotes expression of neuronal genes
Authors: Charbord Jérémie , Poydenot Pauline , Bonnefond Caroline , Feyeux Maxime , Casagrande Fabrice , Brinon Benjamin , Francelle Laetitia , Aurégan Gwenaelle , Guillermier Martine , Cailleret Michel , Viegas Pedro , Nicoleau Camille , Martinat Cécile , Brouillet Emmanuel , Cattaneo Elena , Peschanski Marc , Lechuga Marc , Perrier Anselme L. 
Published: May 2013

Abstract
Decreased expression of neuronal genes such as brain-derived neurotrophic factor (BDNF) is associated with several neurological disorders. One molecular mechanism associated with Huntington disease (HD) is a discrete increase in the nuclear activity of the transcriptional repressor REST/NRSF binding to repressor element-1 (RE1) sequences. High-throughput screening of a library of 6,984 compounds with luciferase-assay measuring REST activity in neural derivatives of human embryonic stem cells led to identify two benzoimidazole-5-carboxamide derivatives that inhibited REST silencing in a RE1-dependent manner. The most potent compound, X5050, targeted REST degradation, but neither REST expression, RNA splicing nor binding to RE1 sequence. Differential transcriptomic analysis revealed the upregulation of neuronal genes targeted by REST in wild-type neural cells treated with X5050. This activity was confirmed in neural cells produced from human induced pluripotent stem cells derived from a HD patient. Acute intraventricular delivery of X5050 increased the expressions of BDNF and several other REST-regulated genes in the prefrontal cortex of mice with quinolinate-induced striatal lesions. This study demonstrates that the use of pluripotent stem cell derivatives can represent a crucial step toward the identification of pharmacological compounds with therapeutic potential in neurological affections involving decreased expression of neuronal genes associated to increased REST activity, such as Huntington disease.
An epigenetic signature of developmental potential in neural stem cells and early neurons
Authors: Burney Matthew J. , Johnston Caroline , Wong Kee-Yew , Teng Siaw-Wei , Beglopoulos Vassilios , Stanton Lawrence W , Williams Brenda P , Bithell Angela , Buckley Noel J. 
Published: May 2013

AbstractA cardinal property of neural stem cells (NSCs) is their ability to adopt multiple fates upon differentiation. The epigenome is widely seen as a read-out of cellular potential and a manifestation of this can be seen in embryonic stem cells (ESCs), where promoters of many lineage-specific regulators are marked by a bivalent epigenetic signature comprising trimethylation of both lysine 4 and lysine 27 of histone H3 (H3K4me3 and H3K27me3, respectively). Bivalency has subsequently emerged as a powerful epigenetic indicator of stem cell potential. Here, we have interrogated the epigenome during differentiation of ESC-derived NSCs to immature GABAergic interneurons. We show that developmental transitions are accompanied by loss of bivalency at many promoters in line with their increasing developmental restriction from pluripotent ESC through multipotent NSC to committed GABAergic interneuron. At the NSC stage, the promoters of genes encoding many transcriptional regulators required for differentiation of multiple neuronal subtypes and neural crest appear to be bivalent, consistent with the broad developmental potential of NSCs. Upon differentiation to GABAergic neurons, all non-GABAergic promoters resolve to H3K27me3 monovalency, whereas GABAergic promoters resolve to H3K4me3 monovalency or retain bivalency. Importantly, many of these epigenetic changes occur before any corresponding changes in gene expression. Intriguingly, another group of gene promoters gain bivalency as NSCs differentiate toward neurons, the majority of which are associated with functions connected with maturation and establishment and maintenance of connectivity. These data show that bivalency provides a dynamic epigenetic signature of developmental potential in both NSCs and in early neurons.
TNF, acting through inducibly expressed TNFR2, drives activation and cell cycle entry of c-Kit+ cardiac stem cells in ischemic heart disease
Authors: Al-Lamki Rafia S. , Lu Wanhua , Wang Jun , Yang Jun , Sargeant Timothy J. , Wells Richard , Suo Chenqu , Wright Penny , Goddard Martin , Huang Qunhua , Lebastchi Amir H. , Tellides George , Huang Yingqun , Min Wang , Pober Jordan S. , Bradley John R. 
Published: May 2013

AbstractTNF, signaling through TNFR2, has been implicated in tissue repair, a process that in the heart may be mediated by activated resident cardiac stem cells (CSCs). The objective of our study is to determine whether ligation of TNFR2 can induce activation of resident CSCs in the setting of ischemic cardiac injury. We show that in human cardiac tissue affected by ischemia heart disease (IHD), TNFR2 is expressed on intrinsic CSCs, identified as c-kit+/CD45−/VEGFR2− interstitial round cells, which are activated as determined by entry to cell cycle and expression of Lin-28. Wild-type mouse heart organ cultures subjected to hypoxic conditions both increase cardiac TNF expression and show induced TNFR2 and Lin-28 expression in c-kit+ CSCs that have entered cell cycle. These CSC responses are enhanced by exogenous TNF. TNFR2−/− mouse heart organ cultures subjected to hypoxia increase cardiac TNF but fail to induce CSC activation. Similarly, c-kit+ CSCs isolated from mouse hearts exposed to hypoxia or TNF show induction of Lin-28, TNFR2, cell cycle entry, and cardiogenic marker, α-sarcomeric actin (α-SA), responses more pronounced by hypoxia in combination with TNF. Knockdown of Lin-28 by siRNA results in reduced levels of TNFR2 expression, cell cycle entry, and diminished expression of α-SA. We conclude that hypoxia-induced c-kit+ CSC activation is mediated by TNF/TNFR2/Lin-28 signaling. These observations suggest that TNFR2 signaling in resident c-kit+ CSCs induces cardiac repair, findings which provide further understanding of the unanticipated harmful effects of TNF blockade in human IHD.
Expression levels of endoglin distinctively identify hematopoietic and endothelial progeny at different stages of yolk sac hematopoiesis
Authors: Borges Luciene , Iacovino Michelina , Koyano-Nakagawa Naoko , Baik June , Garry Daniel J. , Kyba Michael , Perlingeiro Rita C. R. 
Published: May 2013

AbstractEndoglin (Eng), an ancillary receptor of the transforming growth factor beta (TGFβ) signaling pathway superfamily, has been well recognized for its important function in vascular development and angiogenesis since its discovery more than a decade ago. Recent studies show that this receptor is also critical for the emergence of blood during embryonic development, and that at E7.5, endoglin together with Flk-1 identifies early mesoderm progenitors that are endowed with hematopoietic and endothelial potential. These two lineages emerge in very close association during embryogenesis, and because they share the expression of the same surface markers, it has been difficult to distinguish the earliest hematopoietic from endothelial cells. Here, we evaluated the function of endoglin in hematopoiesis as development progresses past E7.5, and found that the hematopoietic and endothelial progenitors can be distinguished by the levels of endoglin in E9.5 yolk sacs. Whereas endothelial cells are Engbright, hematopoietic activity is primarily restricted to a subset of cells that display dim expression of endoglin (Engdim). Molecular characterization of these subfractions showed that endoglin-mediated induction of hematopoiesis occurs in concert with BMP2/BMP4 signaling. This pathway is highly active in Engdim cells but significantly downregulated in the Eng knockout. Taken together, our findings show an important function for endoglin in mediating BMP2/BMP4 signaling during yolk sac hematopoietic development and suggest that the levels of this receptor modulate TGFβ versus bone morphogenetic protein (BMP) signaling.
Parallel assessment of globin lentiviral transfer in induced pluripotent stem cells and adult hematopoietic stem cells derived from the same transplanted β-thalassemia patient
Authors: Tubsuwan Alisa , Abed Soumeya , Deichmann Annette , Kardel Melanie D. , Bartholomä Cynthia , Cheung Alice , Negre Olivier , Kadri Zahra , Fucharoen Suthat , Kalle Christof , Payen Emmanuel , Chrétien Stany , Schmidt Manfred , Eaves Connie J. , Leboulch Philippe , Maouche-Chrétien Leïla 
Published: May 2013

Abstract
A patient with βE/β0-thalassemia major was converted to transfusion-independence 4.5 years ago by lentiviral gene transfer in hematopoietic stem cells while showing a myeloid-biased cell clone. Induced pluripotent stem cells (iPSCs) are a potential alternative source of hematopoietic stem cells. If fetal to adult globin class, switching does not occur in vivo in iPSC-derived erythroid cells, β-globin gene transfer would be unnecessary. To investigate both vector integration skewing and the potential use of iPSCs for the treatment of thalassemia, we derived iPSCs from the thalassemia gene therapy patient and compared iPSC-derived hematopoietic cells to their natural isogenic somatic counterparts. In NSG immunodeficient mice, embryonic to fetal and a partial fetal to adult globin class switching were observed, indicating that the gene transfer is likely necessary for iPSC-based therapy of the β-hemoglobinopathies. Lentivector integration occurred in regions of low and high genotoxicity. Surprisingly, common integration sites (CIS) were identified across those iPSCs and cells retrieved from isogenic and nonisogenic gene therapy patients with β-thalassemia and adrenoleukodystrophy, respectively. This suggests that CIS observed in the absence of overt tumorigenesis result from nonrandom lentiviral integration rather than oncogenic in vivo selection. These findings bring the use of iPSCs closer to practicality and further clarify our interpretation of genome-wide lentivector integration.
Polycomb group gene Ezh2 regulates mammary gland morphogenesis and maintains the luminal progenitor pool
Authors: Michalak Ewa Malgorzata , Nacerddine Karim , Pietersen Alexandra , Beuger Vincent , Pawlitzky Inka , Cornelissen-Steijger Paulien , Wientjens Ellen , Tanger Ellen , Seibler Jost , van Lohuizen Maarten , Jonkers Jos 
Published: May 2013

Abstract
Specification of the cellular hierarchy in the mammary gland involves complex signaling that remains poorly defined. Polycomb group proteins are known to contribute to the maintenance of stem cell identity through epigenetic modifications, leading to stable alterations in gene expression. The polycomb protein family member EZH2 is known to be important for stem cell maintenance in multiple tissues, but its role in mammary gland development and differentiation remains unknown. Our analyses show that EZH2 is predominantly expressed in luminal cells of the mouse mammary epithelium. As mammary gland development occurs mostly after birth, the analysis of EZH2 gene function in postnatal development is precluded by embryonic lethality of conventional EZH2 knockout mice. To investigate the role of EZH2 in normal mammary gland epithelium, we have generated novel transgenic mice that express doxycycline-regulatable short hairpin (sh) RNAs directed against Ezh2. Knockdown of EZH2 results in delayed outgrowth of the mammary epithelium during puberty, due to impaired terminal end bud formation and ductal elongation. Furthermore, our results demonstrate that EZH2 is required to maintain the luminal cell pool and may limit differentiation of luminal progenitors into CD61+ differentiated luminal cells, suggesting a role for EZH2 in mammary luminal cell fate determination. Consistent with this, EZH2 knockdown reduced lobuloalveolar expansion during pregnancy, suggesting EZH2 is required for the differentiation of luminal progenitors to alveolar cells.Stem Cells 2013;31:1910-1920
Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2
Authors: Wang Ying , Dong Jie , Li Dali , Lai Li , Siwko Stefan , Li Yi , Liu Mingyao 
Published: May 2013

Abstract
The key signaling networks regulating mammary stem cells are poorly defined. The leucine-rich repeat containing G protein-coupled receptor (Lgr) family has been implicated in intestinal, gastric, and epidermal stem cell functions. We investigated whether Lgr4 functions in mammary gland development and mammary stem cells. We found that Lgr4−/− mice had delayed ductal development, fewer terminal end buds, and decreased side-branching. Crucially, the mammary stem cell repopulation capacity was severely impaired. Mammospheres from Lgr4−/− mice showed decreased Wnt signaling. Wnt3a treatment prevented the adverse effects of Lgr4 loss on organoid formation. Chromatin immunoprecipitation analysis indicated that Sox2 expression was controlled by the Lgr4/Wnt/β-catenin/Lef1 pathway. Importantly, Sox2 overexpression restored the in vivo mammary regeneration potential of Lgr4−/− mammary stem cells. Therefore, Lgr4 activates Sox2 to regulate mammary development and stem cell functions via Wnt/β-catenin/Lef1.
Isolated fetal pyelectasis and the risk of Down syndrome: a meta‐analysis
Authors: Orzechowski K. M. , Berghella V. 
Published: May 2013

ABSTRACTObjectivesWe performed a meta‐analysis to examine the performance of second‐trimester (14–24 weeks' gestation) isolated fetal pyelectasis as a marker for trisomy 21 and to calculate its associated weighted pooled likelihood ratios.MethodsPubMed, Ovid MEDLINE and Cochrane databases were searched using the terms ‘pyelectasis’ and ‘pelviectasis’. Studies were included if fetuses with isolated pyelectasis were reported separately from fetuses with other soft markers of aneuploidy and/or structural anomalies and if knowledge of the fetal karyotype was unknown at the time of ultrasound examination.ResultsIndividual study statistics were pooled as weighted positive and negative likelihood ratios with 95% CIs, using a random‐effects model. Ten observational studies were included (2148 cases of isolated pyelectasis). Isolated fetal pyelectasis was defined in seven out of 10 studies as a renal pelvis anteroposterior diameter of ≥ 4 mm. Isolated fetal pyelectasis was associated with pooled positive and negative likelihood ratios of 2.78 (95% CI, 1.75–4.43) and 0.99 (95% CI, 0.98–1.00), respectively.ConclusionsThe detection of isolated fetal pyelectasis on mid‐trimester ultrasound is associated with an increased likelihood of trisomy 21. If the finding of isolated fetal pyelectasis is used to adjust the trisomy 21 risk from maternal serum screening tests, a positive likelihood ratio of 2.78 should be used in the calculation. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.