Lineage-specific combinatorial action of enhancers regulates mouse erythroid Gata1 expression.

Precise spatiotemporal control of Gata1 expression is required in both early hematopoietic progenitors to determine erythroid/megakaryocyte versus granulocyte/monocyte lineage output and in the subsequent differentiation of erythroid cells and megakaryocytes. An enhancer element upstream of the mouse Gata1 IE (1st exon erythroid) promoter, mHS-3.5, can direct both erythroid and megakaryocytic expression. However, loss of this element ablates only megakaryocytes, implying that an additional element has erythroid specificity. Here, we identify a double DNaseI hypersensitive site, mHS-25/6, as having erythroid but not megakaryocytic activity in primary cells. It binds an activating transcription factor complex in erythroid cells where it also makes physical contact with the Gata1 promoter. Deletion of mHS-25/6 or mHS-3.5 in embryonic stem cells has only a modest effect on in vitro erythroid differentiation, whereas loss of both elements ablates both primitive and definitive erythropoiesis with an almost complete loss of Gata1 expression. Surprisingly, Gata2 expression was also concomitantly low, suggesting a more complex interaction between these 2 factors than currently envisaged. Thus, whereas mHS-3.5 alone is sufficient for megakaryocytic development, mHS-3.5 and mHS-25/6 collectively regulate erythroid Gata1 expression, demonstrating lineage-specific differences in Gata1 cis-element use important for development of these 2 cell types.

High-impact conservation: invasive mammal eradications from the islands of western México.

Islands harbor a disproportionate amount of the earth's biodiversity, but a significant portion has been lost due in large part to the impacts of invasive mammals. Fortunately, invasive mammals can be routinely removed from islands, providing a powerful tool to prevent extinctions and restore ecosystems. Given that invasive mammals are still present on more than 80% of the world's major islands groups and remain a premier threat to the earth's biodiversity, it is important to disseminate replicable, scaleable models to eradicate invasive mammals from islands. We report on a successful model from western México during the past decade. A collaborative effort between nongovernmental organizations, academic biologists, Mexican government agencies, and local individuals has resulted in major restoration efforts in three island archipelagos. Forty-two populations of invasive mammals have been eradicated from 26 islands. For a cost of USD 21,615 per colony and USD 49,370 per taxon, 201 seabird colonies and 88 endemic terrestrial taxa have been protected, respectively. These conservation successes are a result of an operational model with three main components: i) a tri-national collaboration that integrates research, prioritization, financing, public education, policy work, capacity building, conservation action, monitoring, and evaluation; ii) proactive and dedicated natural resource management agencies; and iii) effective partnerships with academic researchers in Mexico and the United States. What is now needed is a detailed plan to eradicate invasive mammals from the remaining islands in the region that integrates the needed additional financing, capacity, technical advances, and policy issues. Island conservation in western Mexico provides an effective approach that can be readily applied to other archipelagos where conservation efforts have been limited.

Long-range regulation of alpha-globin gene expression.

Over the past 20 years, there has been an increasing awareness that gene expression can be regulated by multiple cis-acting sequences located at considerable distances (10-1000 kb) from the genes they control. Detailed investigation of a few specialized mammalian genes, including the genes controlling the synthesis of hemoglobin, provide important models to understand how such long-range regulatory elements act. In general, these elements contain a high density of evolutionarily conserved, transcription factor-binding sites and in many ways resemble the upstream regulatory elements found adjacent to the promoters of genes in simpler organisms, differing only in the distance over which they act. We have investigated in detail how the remote regulatory elements of the alpha-globin cluster become activated as hematopoietic stem cells (HSCs) undergo commitment, lineage specification, and differentiation to form red blood cells. In turn, we have addressed how, during this process, the upstream elements control the correct spatial and temporal expression from the alpha-gene promoter which lies approximately 60 kb downstream of these elements. At present too few loci have been studied to determine whether there are general principles underlying long-range regulation but some common themes are emerging.

Electrocatalytic reactions mediated by N,N,N',N'-Tetraalkyl-1,4-phenylenediamine redox liquid microdroplet-modified electrodes: chemical and photochemical reactions In, and At the surface of, femtoliter droplets.

The electro-oxidation of electrolytically unsupported ensembles of N,N-diethyl-N',N'-dialkyl-para-phenylenediamine (DEDRPD, R = n-butyl, n-hexyl, and n-heptyl) redox liquid femtoliter volume droplets immobilized on a basal plane pyrolytic graphite electrode is reported in the presence of aqueous electrolytes. Electron transfer at these redox liquid modified electrodes is initiated at the microdroplet-electrode-electrolyte three-phase boundary. Dependent on both the lipophilicity of the redox oil and that of the aqueous electrolyte, ion uptake into or expulsion from the organic deposits is induced electrolytically. In the case of hydrophobic electrolytes, redox-active ionic liquids are synthesized, which are shown to catalyze the oxidation of l-ascorbic acid over the surface of the droplets. In contrast, the photoelectrochemical reduction of the anaesthetic reagent halothane proceeds within the droplet deposits and is mediated by the ionic liquid precursor (the DEDRPD oil).