In The Meantime Men’s Group

Hematopoiesis is a highly dynamical and stochastic process, challenging our understanding of homeostasis. Clinical studies of leukemia or neutropenic patients revealed that multiple blood cell types fluctuate spontaneously with large yet regular oscillations of their frequencies. Yet the stability of hematopoiesis in healthy individuals remains understudied. Here we report on both cross-sectional and longitudinal studies of dozens of healthy mice, through high-dimensional mass and spectral cytometry, to understand hematopoiesis at homeostasis. We found that all cell types in the bone marrow, blood, and spleen exhibit large variations of frequency (e.g., with coefficients of variation larger than 1). While the frequencies of individual cell type fluctuate, there existed extensive and robust correlations/anti-correlations between cell types, exemplified by the pronounced anti-correlation between blood neutrophils and B cells. Through longitudinal study of the blood content of healthy mice, we found that leukocyte fluctuations are ergodic yet subject to chaotic behaviors characterized by a broad spectrum of characteristic timescales. We then built a minimal mathematical model to capture these dynamical features of hematopoiesis (fluctuations, correlations, and chaos) and explain how the accumulation of B cells (e.g. during lymphoma development) would transition the blood cell dynamics from chaos to oscillations (as observed clinically). Finally, we demonstrated the ubiquity and consistency of the correlated fluctuations in hematopoiesis by comparing mouse cohorts of different genetic backgrounds and ages. To conclude, we discuss how study of hematopoiesis must factor in the newfound chaotic dynamics at homeostasis, towards better modeling the responses to perturbations.

RSV infects nearly all children by age 2, and typically causes mild host symptoms. Susceptible individuals develop severe lower respiratory tract infections and bronchiolitis, often leading to hospitalization or death. Clinical treatment often requires therapeutic oxygen. Previous studies showed that hyperoxia (>;95% O2) causes up‐regulation of TLR4, which has been implicated in host susceptibility and response to RSV infection. We hypothesized that hyperoxia enhances susceptibility and response to RSV infection in bronchial epithelial cells and inbred mice, and this effect is mediated by TLR4. BEAS‐2B cells were exposed to hyperoxia 18 hr and then infected with RSV. Cells were analyzed for markers of viral infection and pattern recognition receptors. Compared to air, hyperoxia caused a 4‐fold increase in viral load and increased TLR4 expression in cells 48 and 72 hr PI. C57BL/6J (WT) and C57BL/6J‐TLR4−/− mice were exposed to hyperoxia or air for 24 hr and 24 hr later were infected with a single dose of RSV or Hep 2.Viral load peaked 5 d PI in both strains however RSV in WT mice was significantly higher compared to TLR4−/− 1–5 d PI. Results indicate that hyperoxia enhanced susceptibility to RSV infection and exacerbated the resulting response, and this effect is partially mediated through TLR4. Support by NIEHS intramural research program.

Extracts of Curcuma comosa, a plant in the Zingiberaceae family, exert estrogenic activity in in vivo and in vitro assays. Diarylheptanoids, a major component of C. comosa, are estrogenic in rat uterine bioassays, in an estrogen responsive yeast two‐hybrid system, and in MCF‐7 (human breast cancer) cells. This study aims to characterize further the estrogenic activity of C. comosa‐derived diarylheptanoids. HepG2 cells expressing wild type or mutant forms of the mouse estrogen receptor‐α (ERα) and possessing an estrogen responsive reporter plasmid (3XERE‐TATA‐Luc) were exposed to increasing doses of diarylheptanoids. At 50 μM, the diarylheptanoids were equally efficient as 1 nM estradiol at stimulating ERE‐driven reporter activity, and this response was dose‐dependent. This activity was inhibited by the ER antagonist (ICI‐182780). A mutant ERα lacking the AF2 domain was unresponsive to the diarylheptanoids, while ERα lacking the AF1 domain exhibited wild type‐like activity. These data indicate that diarylheptanoids are active in an ER‐dependent system and this activity is dependent on ERα, more specifically its AF2 function. We therefore surmise that diarylheptanoids contribute to the estrogenic activity of C. comosa.Supported by Thailand Research Fund through Royal Golden Jubilee PhD Program (PHD/0255/2546) to WT and PP; BIOTEC grant to AS; NIEHS Division of Intramural Research Funding to WT, YA, SCH and KSK.

Anthropology NewsVolume 42, Issue 1 p. 49-49 Association for Political and Legal Anthropology Bill Maurer, Bill Maurer Contributing Editor It is in the spirit of re-thinking the subdiscipline that I open the column to interested contributors from APLA or elsewhere, as we debate the future of political and legal anthropology. Please send all contributions to me at the Department of Anthropology, U of California, Irvine, CA 92697–5100 or wmmaurer@uci.edu (email strongly preferred!). In the meantime, be sure to watch for the next issue of PoLAR: The Political and Legal Anthropology Review, and visit our association web-page, http:www.ameranthassn.orgaplaindex.htm.Search for more papers by this author Bill Maurer, Bill Maurer Contributing Editor It is in the spirit of re-thinking the subdiscipline that I open the column to interested contributors from APLA or elsewhere, as we debate the future of political and legal anthropology. Please send all contributions to me at the Department of Anthropology, U of California, Irvine, CA 92697–5100 or wmmaurer@uci.edu (email strongly preferred!). In the meantime, be sure to watch for the next issue of PoLAR: The Political and Legal Anthropology Review, and visit our association web-page, http:www.ameranthassn.orgaplaindex.htm.Search for more papers by this author First published: 07 July 2009 https://doi.org/10.1111/an.2001.42.1.49.1 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume42, Issue1January 2001Pages 49-49 RelatedInformation