Identification of the niche and phenotype of the first human hematopoietic stem cells

SummaryIn various vertebrate species, the dorsal aorta (Ao) is the site of specification of adult hematopoietic stem cells (HSCs). It has been observed that the upregulation of essential hematopoietic transcription factors and the formation of specific intra-aortic hematopoietic cell clusters occur predominantly in the ventral domain of the Ao (AoV). In the mouse, the first HSCs emerge in the AoV. Here, we demonstrate that in the human embryo the first definitive HSCs also emerge asymmetrically and are localized to the AoV, which thus identifies a functional niche for developing human HSCs. Using magnetic cell separation and xenotransplantations, we show that the first human HSCs are CD34+VE-cadherin+CD45+C-KIT+THY-1+Endoglin+RUNX1+CD38−/loCD45RA−. This population harbors practically all committed hematopoietic progenitors and is underrepresented in the dorsal domain of the Ao (AoD) and urogenital ridges (UGRs). The present study provides a foundation for analysis of molecular mechanisms underpinning embryonic specification of human HSCs

Arrival Time Statistics in Global Disease Spread

Metapopulation models describing cities with different populations coupled by the travel of individuals are of great importance in the understanding of disease spread on a large scale. An important example is the Rvachev-Longini model [{\it Math. Biosci.} {\bf 75}, 3-22 (1985)] which is widely used in computational epidemiology. Few analytical results are however available and in particular little is known about paths followed by epidemics and disease arrival times. We study the arrival time of a disease in a city as a function of the starting seed of the epidemics. We propose an analytical Ansatz, test it in the case of a spreading on the world wide air transportation network, and show that it predicts accurately the arrival order of a disease in world-wide cities

Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis

The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs), which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs), which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK) signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior

Photocatalytic Coats in Glass Drinking-Water Bottles

According to a proposal, the insides of glass bottles used to store drinking water would be coated with films consisting of or containing TiO2. In the presence of ultraviolet light, these films would help to remove bacteria, viruses, and trace organic contaminants from the water

Patient and physician perceptions of their relationship and patient satisfaction: A study of chronic disease management

This study investigated patient and physician perceptions of their relationship and examined how their perceptions related to patient satisfaction. Data are based on 134 patient physician interactions. Study participants included 12 physicians (five women and seven men) and 134 male patients with a diagnosis of diabetes mellitus being seen on an outpatient basis. Information on patient and physician demographics, patient's metabolic control and functional status and time spent in the interaction were also collected. Results revealed that patients with lower levels of education were most satisfied and that physicians who viewed the relationship as a patient physician partnership had more satisfied patients than those who viewed the relationship as physician controlled. Findings also indicated that physicians' gender and number of years in practice were not related to patient satisfaction. Practical implications include: (1) increasing attention to physician's perceptions of his or her relationship with individual patients and (2) exposing newly trained physicians to partnership types of relationships, if future research confirms these findings in chronic disease management.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31021/1/0000697.pd

Epidemic variability in complex networks

We study numerically the variability of the outbreak of diseases on complex networks. We use a SI model to simulate the disease spreading at short times, in homogeneous and in scale-free networks. In both cases, we study the effect of initial conditions on the epidemic's dynamics and its variability. The results display a time regime during which the prevalence exhibits a large sensitivity to noise. We also investigate the dependence of the infection time on nodes' degree and distance to the seed. In particular, we show that the infection time of hubs have large fluctuations which limit their reliability as early-detection stations. Finally, we discuss the effect of the multiplicity of shortest paths between two nodes on the infection time. Furthermore, we demonstrate that the existence of even longer paths reduces the average infection time. These different results could be of use for the design of time-dependent containment strategies

Decreased sex ratio following maternal exposure to polychlorinated biphenyls from contaminated Great Lakes sport-caught fish: a retrospective cohort study.

BACKGROUND: Fish from the Great Lakes are contaminated with polychlorinated biphenyls, which have been found to have several adverse reproductive effects. Several environmental contaminants have been found to alter the sex ratio of offspring at birth, but the evidence of such an effect of polychlorinated biphenyls has been inconsistent. METHODS: We examined parental serum polychlorinated biphenyl concentration in relation to the sex ratio of 173 children of mothers and 208 children of fathers from the Great Lakes region of the United States between 1970 and 1995. We calculated odds ratios for a male child using logistic regression and generalized estimating equations with adjustment for the year of birth of the child, maternal and paternal age, the mother's parity at the child's birth, and whether the child had an older brother. RESULTS: The adjusted odds ratio for having a male child among mothers in the highest quintile of serum polychlorinated biphenyl concentration was 0.18 (95% CI: 0.06–0.59) compared to mothers in the lowest quintile. Treating exposure as a continuous variable, the adjusted odds ratio for having a male child was 0.54 per unit increase in the natural log of maternal serum polychlorinated biphenyl concentration (95% CI: 0.33–0.89). There was little evidence of an association with paternal exposure. We found no association between either maternal or paternal serum dichlorodiphenyl-dichloroethene concentration and the sex ratio. CONCLUSIONS: These findings suggest that maternal exposure to polychlorinated biphenyls may decrease the sex ratio of offspring. These data add to the growing body of evidence that exposure to particular chemicals can alter the sex ratio at birth

Arsenic and Bacteriophage MS2 Removal from Groundwater by Nanoparticulate Aluminum Oxide Coated Granular Filter Media: A Pilot-Scale Evaluation on the Effect of pH and Coating Density

Ope

Commitment to an Emerging Organizational Field, Institutional Entrepreneurship, and the Perception of Opportunity: An Enactment Theory

Given an indifferent institutional environment, ongoing commitment to an emerging organizational field is critical. We build and test an enactment theory of commitment that holds that commitment is driven by institutional entrepreneurship, specifically actions to educate stakeholders, but that this factor is mediated by perception of an opportunity that rests on beliefs in industry attractiveness, superior products and services, and the likelihood of disruptive exogenous change. We illustrate this theory with findings from surveys of energy efficiency and renewable energy businesses. The results highlight the central role of actions to educate stakeholders. When an institutional domain is not yet fully established, the effect of entrepreneurs' actions to educate stakeholders is not just external, but has an important inward function of bolstering the entrepreneurs' ongoing commitment to the emerging field