Issues and options related to management of Silver Springs rhesus macaques

Management options for the Silver Springs free-ranging rhesus macaque population range from removal to active maintenance of the population in situ. Selection of a management option is dependent upon which issues are perceived to be true problems. Management options are presented along with their effectiveness in dealing with issues previously described.(31 page document

Concerted bioinformatic analysis of the genome-scale blood transcription factor compendium reveals new control mechanisms.

Transcription factors play a key role in the development of a disease. ChIP-sequencing has become a preferred technique to investigate genome-wide binding patterns of transcription factors in vivo. Although this technology has led to many important discoveries, the rapidly increasing number of publicly available ChIP-sequencing datasets still remains a largely unexplored resource. Using a compendium of 144 publicly available murine ChIP-sequencing datasets in blood, we show that systematic bioinformatic analysis can unravel diverse aspects of transcription regulation; from genome-wide binding preferences, finding regulatory partners and assembling regulatory complexes, to identifying novel functions of transcription factors and investigating transcription dynamics during development.This is the final published version as published by the Royal Society of Chemistry in Molecular Biosystems here: http://pubs.rsc.org/en/Content/ArticleLanding/2014/MB/C4MB00354C#divAbstract

Mammalian Transcription Factor Networks: Recent Advances in Interrogating Biological Complexity

Transcription factor (TF) networks are a key determinant of cell fate decisions in mammalian development and adult tissue homeostasis and are frequently corrupted in disease. However, our inability to experimentally resolve and interrogate the complexity of mammalian TF networks has hampered the progress in this field. Recent technological advances, in particular large-scale genome-wide approaches, single-cell methodologies, live-cell imaging, and genome editing, are emerging as important technologies in TF network biology. Several recent studies even suggest a need to re-evaluate established models of mammalian TF networks. Here, we provide a brief overview of current and emerging methods to define mammalian TF networks. We also discuss how these emerging technologies facilitate new ways to interrogate complex TF networks, consider the current open questions in the field, and comment on potential future directions and biomedical applications.ACW is funded by a Bloodwise Visiting Fellowship. HN is funded by the Japan Science and Technology Agency, the California Institute of Regenerative Medicine and Ludwig Foundation. BG is funded by Bloodwise, Cancer Research UK, the Wellcome Trust, the MRC, NIH-NIDDK and core funding from the Wellcome Trust to the Cambridge Stem Cell Institute

Improved arteriogenesis with simultaneous skeletal muscle repair in ischemic tissue by SCL plus multipotent adult progenitor cell clones from peripheral blood

Background: The CD34- murine stem cell line RM26 cloned from peripheral blood mononuclear cells has been shown to generate hematopoietic progeny in lethally irradiated animals. The peripheral blood-derived cell clones expresses a variety of mesodermal and erythroid/myeloid transcription factors suggesting a multipotent differentiation potential like the bone marrow-derived `multipotent adult progenitor cells' (MAP-C). Methods: SCL+ CD34- RM26 cells were transfused intravenously into mice suffering from chronic hind-limb ischemia, evaluating the effect of stem cells on collateral artery growth and simultaneous skeletal muscle repair. Results: RM26 cells are capable of differentiating in vitro into endothelial cells when cultured on the appropriate collagen matrix. Activation of the SCL stem cell enhancer (SCL+) is mediated through the binding to two Ets and one GATA site and cells start to express milieu- and growth condition-dependent levels of the endothelial markers CD31 (PECAM) and Flt-1 (VEGF-R1). Intravenously infused RM26 cells significantly improved the collateral blood flow (arteriogenesis) and neo-angiogenesis formation in a murine hind-limb ischemia transplant model. Although transplanted RM26 cells did not integrate into the growing collateral arteries, cells were found adjacent to local arteriogenesis, but instead integrated into the ischemic skeletal muscle exclusively in the affected limb for simultaneous tissue repair. Conclusion: These data suggest that molecularly primed hem-/mesangioblast-type adult progenitor cells can circulate in the peripheral blood improving perfusion of tissues with chronic ischemia and extending beyond the vascular compartment. Copyright (C) 2004 S. Karger AG, Basel

Girl??? I'm a woman now! : a six year photographic documentary focusing on twelve teenage girls and their transition into adulthood

This photographic documentary seeks to record the transition from teenager into adulthood of twelve girls living in Melbourne, Australia between 2002 and 2008. Throughout the process of the project the artist has sought to challenge the assumption that reaching adulthood can be defined by achieving certain milestones in society, and that the transition period is as much about personal self-realisation on the part of the individual, as it is about measurements set by society. The photographic work is accompanied by text in the form of quotes taken from audio interviews conducted throughout the documentation process. This paper compares the ideas set by society about the process of becoming an adult and the real life events that triggered this transition period in this particular group of girls

The Paraguay-Paraná Hidrovía: Protecting the Pantanal with Lessons from the Past: Large-scale channelization of the northern Paraguay-Paraná seems to be on hold, but an ongoing multitude of smaller-scale activities may turn the Pantanal into the next example of the “tyranny of small decisions”

Because it is one of the most inaccessible places on earth, this large, rich ecosystem has remained relatively untouched. There is, however, increasing evidence that this area is threatened by a number of activities, including mining, illegal hunting and fishing, indiscriminate use of fire, agricultural development, and deforestation. Careless use of mercury in gold mining, particularly in the northern Pantanal, may have resulted in acute and chronic ecosystem disruption (Hylander et al. 1994, Nogueira et al. 1997, Leady and Gottgens 2001). Wildlife poaching and live animal trade are widespread although hard to quantify. During six months in 1985, the skins of an estimated 500,000 animals, including jaguars, maned wolves, caimans, and snakes were exported to Europe, Asia, and North America (Anonymous 1985). Pet collectors focus on a variety of animals, including monkeys, parrots, and macaws. A pair of hyacinth macaws has a market value between US$8,000 and US$10,000 in the United States and Europe (Mittermeier et al. 1990). Only a fraction of this trade is confiscated and, although enforcement has improved, the majority of offenders are never captured

TRES predicts transcription control in embryonic stem cells.

SUMMARY: Unraveling transcriptional circuits controlling embryonic stem cell maintenance and fate has great potential for improving our understanding of normal development as well as disease. To facilitate this, we have developed a novel web tool called 'TRES' that predicts the likely upstream regulators for a given gene list. This is achieved by integrating transcription factor (TF) binding events from 187 ChIP-sequencing and ChIP-on-chip datasets in murine and human embryonic stem (ES) cells with over 1000 mammalian TF sequence motifs. Using 114 TF perturbation gene sets, as well as 115 co-expression clusters in ES cells, we validate the utility of this approach. AVAILABILITY AND IMPLEMENTATION: TRES is freely available at http://www.tres.roslin.ed.ac.uk. CONTACT: [email protected] or [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.This work was supported by a University of Edinburgh Chancellors Fellowship awarded to AJ and strategic funding from the BBSRC. CP was funded by the Scottish Government through the Strategic Partnership for Animal Science Excellence (SPASE). The Gottgens’ lab is supported by LLR, the MRC, BBSRC, Cancer Research UK, and Wellcome Trust core support to the Cambridge Institute for Medical Research and Wellcome Trust–MRC Cambridge Stem Cell Institute.This version is the author accepted manuscript. The published advanced access version can be viewed on the journals website at: http://bioinformatics.oxfordjournals.org/content/early/2014/06/23/bioinformatics.btu399.full.pdf+htm

UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs.

The H3K27 lysine-specific demethylase UTX is targeted by loss-of-function mutations in multiple cancers. Here, we demonstrate that UTX suppresses myeloid leukemogenesis through non-catalytic functions, a property shared with its catalytically inactive Y-chromosome paralogue, UTY. In keeping with this, we demonstrate concomitant loss/mutation of UTX and UTY in multiple human cancers. Mechanistically, global genomic profiling revealed only minor changes in H3K27Me3, but significant and bidirectional alterations of H3K27Ac and chromatin accessibility, a predominant loss of H3K4Me1 modifications, alterations in ETS and GATA factor binding and altered gene expression upon Utx loss. By integrating proteomic and genomic analyses, we link these changes to UTX regulation of ATP-dependent chromatin remodeling, coordination of the COMPASS complex and enhanced pioneering activity of ETS factors during evolution to AML. Collectively, our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor-suppressive GATA programsThis study was primarily funded by a joint Bloodwise Program Grant (17006) to B.H. and G.S.V. Work in the Huntly lab is also funded by an ERC consolidator award (grant 647685 COMAL), a CRUK program award, the Medical Research Council, (MRC) the Welcome Trust (WT) and the Cambridge NIHR BRC. We acknowledge the WT/MRC center grant (097922/Z/11/Z) and support from WT strategic award 100140. G.S.V. is funded by a Cancer Research UK Senior Cancer Research Fellowship (C22324/A23015). The Vassiliou laboratory is also supported by the Kay Kendall Leukemia Fund and core funding from the Sanger Institute (WT098051)

Mbd3/NuRD controls lymphoid cell fate and inhibits tumorigenesis by repressing a B cell transcriptional program

Differentiation of lineage-committed cells from multipotent progenitors requires establishment of accessible chromatin at lineage-specific transcriptional enhancers and promoters, which is mediated by pioneer transcription factors that recruit activating chromatin remodeling complexes. Here we show that the Mbd3/NuRD chromatin remodeling complex opposes this transcriptional pioneering during B cell programming of multipotent lymphoid progenitors by restricting chromatin accessibility at B cell enhancers and promoters. Mbd3/NuRD-deficient lymphoid progenitors therefore prematurely activate a B cell transcriptional program and are biased towards overproduction of pro-B cells at the expense of T cell progenitors. The striking reduction in early thymic T cell progenitors results in compensatory hyperproliferation of immature thymocytes and development of T cell lymphoma. Our results reveal that Mbd3/NuRD can regulate multilineage differentiation by constraining the activation of dormant lineage-specific enhancers and promoters. In this way, Mbd3/NuRD protects the multipotency of lymphoid progenitors, preventing B cell-programming transcription factors from prematurely enacting lineage commitment. Mbd3/NuRD therefore controls the fate of lymphoid progenitors, ensuring appropriate production of lineage-committed progeny and suppressing tumour formation.F.C. was supported by an EMBO long-term fellowship (1305-2015 and Marie Curie Actions LTFCOFUND2013/GA-2013-609409). Work in the Green lab is supported Cancer Research UK (grants refs. C1163/A12765 and C1163/A12526), Bloodwise (grant ref. 13003), and core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research (100140/Z/12/Z) and Wellcome Trust-MRC Cambridge Stem Cell Institute (097922/Z/11/Z)