Characterization of a distinct population of circulating human non-adherent endothelial forming cells and their recruitment via intercellular adhesion molecule-3

Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133+ population of non-adherent endothelial forming cells (naEFCs) which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38) together with mature endothelial cell markers (VEGFR2, CD144 and CD31). These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8)or myeloid markers (CD11b and CD14) which distinguishes them from ‘early’ endothelial progenitor cells (EPCs). Functional studies demonstrated that these naEFCs (i) bound Ulex europaeus lectin, (ii)demonstrated acetylated-low density lipoprotein uptake, (iii) increased vascular cell adhesion molecule (VCAM-1) surface expression in response to tumor necrosis factor and (iv) in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3- dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs). Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM)-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis.Sarah L. Appleby, Michaelia P. Cockshell, Jyotsna B. Pippal, Emma J. Thompson, Jeffrey M. Barrett, Katie Tooley, Shaundeep Sen, Wai Yan Sun, Randall Grose, Ian Nicholson, Vitalina Levina, Ira Cooke, Gert Talbo, Angel F. Lopez and Claudine S. Bonde

Gender gap in parental leave intentions: Evidence from 37 countries

This is the final version. Available from Wiley via the DOI in this record. Despite global commitments and efforts, a gender-based division of paid and unpaid work persists. To identify how psychological factors, national policies, and the broader sociocultural context contribute to this inequality, we assessed parental-leave intentions in young adults (18–30years old) planning to have children (N = 13,942; 8,880 identified as women; 5,062 identified as men) across 37 countries that varied in parental-leave policies and societal gender equality. In all countries, women intended to take longer leave than men. National parental-leave policies and women’s political representation partially explained cross-national variations in the gender gap. Gender gaps in leave intentions were paradoxically larger in countries with more gender-egalitarian parental-leave policies (i.e., longer leave available to both fathers and mothers). Interestingly, this cross-national variation in the gender gap was driven by cross-national variations in women’s (rather than men’s) leave intentions. Financially generous leave and gender-egalitarian policies (linked to men’s higher uptake in prior research) were not associated with leave intentions in men. Rather, men’s leave intentions were related to their individual gender attitudes. Leave intentions were inversely related to career ambitions. The potential for existing policies to foster gender equality in paid and unpaid work is discussed.SSHRC Insight Development GrantSSHRC Insight GrantEconomic and Social Research CouncilState Research AgencyGuangdong 13th-five Philosophy and Social Science Planning ProjectNational Natural Science Foundation of ChinaSwiss National Science FoundationSwiss National Science FoundationCenter for Social Conflict and Cohesion StudiesCenter for Intercultural and Indigenous ResearchSSHRC Postdoctoral FellowshipSlovak Research and Development AgencySwiss National Science FoundationCanada Research ChairsSocial Sciences and Humanities Research Council of CanadaOntario Ministry of Research and InnovationHSE University, RFFaculty of Arts, Masaryk Universit

Effects of Endocrine-Disrupting Chemicals on Endometrial Receptivity and Embryo Implantation. A Systematic Review of 34 Mouse Model Studies

Several available studies have already analyzed the systemic effects of endocrine-disrupting chemicals (EDCs) on fertile woman and neonatal outcomes, but little is still known in humans about the precise mechanisms of interference of these compounds with the endometrial receptivity. There is consistent evidence that continuous and prolonged exposure to EDCs is a risk factor for reduced fertility and fecundity in women. Preliminary studies on mammalian models provide robust evidence about this issue and could help gynecologists worldwide to prevent long term injury caused by EDCs on human fertility. In this systematic review, we aimed to systematically summarize all available data about EDC effects on blastocyst endometrial implantation. We performed a systematic review using PubMed®/MEDLINE® to summarize all in vivo studies, carried out on mice models, analyzing the molecular consequences of the prolonged exposure of EDC on the implantation process. 34 studies carried out on mouse models were included. Primary effects of EDC were a reduction of the number of implantation sites and pregnancy rates, particularly after BPA and phthalate exposure. Furthermore, the endometrial expression of estrogen (ER) and progesterone receptors (PR), as well as their activation pathways, is compromised after EDC exposure. Finally, the expression of the primary endometrial markers of receptivity (such as MUC1, HOXA10, Inn and E-cadherin) after EDC contact was analyzed. In conclusion EDC deeply affect blastocyst implantation in mouse model. Several players of the implantation mechanism are strongly influenced by the exposure to different categories of EDC

Acute megakaryoblastic leukemia: experience of GIMEMA trials

September 2002, Volume 16, Number 9, Pages 1622-1626 Table of contents Previous Abstract Next Full text PDF Original Manuscript Acute megakaryoblastic leukemia: experience of GIMEMA trials L Pagano1, A Pulsoni2, M Vignetti2, L Mele1, L Fianchi1, M C Petti2, S Mirto4, P Falcucci2, P Fazi2, G Broccia12, G Specchia7, F Di Raimondo11, L Pacilli9, P Leoni13, S Ladogana8, E Gallo3, A Venditti6, G Avanzi10, A Camera5, V Liso7, G Leone1 and F Mandelli2 for the GIMEMA 1Cattedra di Ematologia, Università Cattolica S. Cuore, Roma, Italy 2Dipartimento di Biotecnologie cellulari ed Ematologia, Università 'La Sapienza', Roma, Italy 3Ematologia Molinette, Ospedale Maggiore 'S Giovanni Battista', Torino, Italy 4Divisione di Ematologia, Ospedale Cervello di Palermo, Italy 5Divisione di Ematologia, II Policlinico, Napoli, Italy 6Istituto di Ematologia, Università di Tor Vergata, Roma, Italy 7Istituto di Ematologia, Università di Bari, Bari, Italy 8Divisione di Ematologia, Ospedale di S Giovanni Rotondo, Italy 9Divisione di Ematologia, Ospedale S Camillo, Roma, Italy 10Divisione di Ematologia, Ospedale di Novara, Italy 11Cattedra di Ematologia, Università di Catania, Italy 12Divisione di Ematologia, Ospedale Cagliari, Italy 13Cattedra di Ematologia, Università di Ancona, Italy Correspondence to: L Pagano, Dept of Haematology, Catholic University, Largo Francesco Vito 1, I-00168 Roma, Italy; Fax: 39063051343 Abstract The objective of the study was to evaluate the incidence, characteristics, treatment and outcome of acute megakaryoblastic leukemia (AMeL) in patients enrolled in GIMEMA trials. Between 1982 and 1999, 3603 new consecutive cases of AML aged over 15 years were admitted to GIMEMA trials. Of them, 24 were AMeL. The incidence of AMeL among AML patients enrolled in GIMEMA trials was 0.6% (243603). Diagnosis was based on morphological criteria. Out of 11 cytogenetic studies performed two presented chromosome 3 abnormalities. Twelve patients (50%) reached a CR, five (21%) died in induction and seven (27%) were unresponsive. The median duration of CR was 35 weeks (range 10441). Seven patients underwent transplantation procedures (1 BMT, 4 aBMT, 2 aPBSCT). Four patients died in CR due to chemotherapy-related complications. Comparing the CR rate between AMeL and the other cases of AML enrolled in GIMEMA trials, no differences were observed. These results were mirrored for different age groups. The median survival was 40 weeks. At present, after a follow-up of a minimum of 2 years, only two patients are alive in CR, all the others having died. A 5-year KaplanMeier curve shows a disease-free survival of 17% and an actuarial overall survival of 10%. AMeL is a rare form of AML. The CR duration and the overall survival in this group of patients are very poor, even if similar to those observed in other AML. Furthermore, a high number of deaths in CR were observed. On the basis of these data, a specific therapeutic approach, possibly with innovative treatments, should be evaluated. Leukemia (2002) 16, 16221626. doi:10.1038/sj.leu.240261