Adapting Urban Water Systems to Manage Scarcity in the 21st Century: The Case of Los Angeles.

Acute water shortages for large metropolitan regions are likely to become more frequent as climate changes impact historic precipitation levels and urban population grows. California and Los Angeles County have just experienced a severe four year drought followed by a year of high precipitation, and likely drought conditions again in Southern California. We show how the embedded preferences for distant sources, and their local manifestations, have created and/or exacerbated fluctuations in local water availability and suboptimal management. As a socio technical system, water management in the Los Angeles metropolitan region has created a kind of scarcity lock-in in years of low rainfall. We come to this through a decade of coupled research examining landscapes and water use, the development of the complex institutional water management infrastructure, hydrology and a systems network model. Such integrated research is a model for other regions to unpack and understand the actual water resources of a metropolitan region, how it is managed and potential ability to become more water self reliant if the institutions collaborate and manage the resource both parsimoniously, but also in an integrated and conjunctive manner. The Los Angeles County metropolitan region, we find, could transition to a nearly water self sufficient system

Amplification of pico-scale DNA mediated by bacterial carrier DNA for small-cell-number transcription factor ChIP-seq

BACKGROUND: Chromatin-Immunoprecipitation coupled with deep sequencing (ChIP-seq) is used to map transcription factor occupancy and generate epigenetic profiles genome-wide. The requirement of nano-scale ChIP DNA for generation of sequencing libraries has impeded ChIP-seq on in vivo tissues of low cell numbers. RESULTS: We describe a robust, simple and scalable methodology for ChIP-seq of low-abundant cell populations, verified down to 10,000 cells. By employing non-mammalian genome mapping bacterial carrier DNA during amplification, we reliably amplify down to 50 pg of ChIP DNA from transcription factor (CEBPA) and histone mark (H3K4me3) ChIP. We further demonstrate that genomic profiles are highly resilient to changes in carrier DNA to ChIP DNA ratios. CONCLUSIONS: This represents a significant advance compared to existing technologies, which involve either complex steps of pre-selection for nucleosome-containing chromatin or pre-amplification of precipitated DNA, making them prone to introduce experimental biases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-014-1195-4) contains supplementary material, which is available to authorized users

Phosphorylation of Serine 248 of C/EBPα Is Dispensable for Myelopoiesis but Its Disruption Leads to a Low Penetrant Myeloid Disorder with Long Latency

BACKGROUND: Transcription factors play a key role in lineage commitment and differentiation of stem cells into distinct mature cells. In hematopoiesis, they regulate lineage-specific gene expression in a stage-specific manner through various physical and functional interactions with regulatory proteins that are simultanously recruited and activated to ensure timely gene expression. The transcription factor CCAAT/enhancer binding protein α (C/EBPα) is such a factor and is essential for the development of granulocytic/monocytic cells. The activity of C/EBPα is regulated on several levels including gene expression, alternative translation, protein interactions and posttranslational modifications, such as phosphorylation. In particular, the phosphorylation of serine 248 of the transactivation domain has been shown to be of crucial importance for granulocytic differentiation of 32Dcl3 cells in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Here, we use mouse genetics to investigate the significance of C/EBPα serine 248 in vivo through the construction and analysis of Cebpa(S248A/S248A) knock-in mice. Surprisingly, 8-week old Cebpa(S248A/S248A) mice display normal steady-state hematopoiesis including unaltered development of mature myeloid cells. However, over time some of the animals develop a hematopoietic disorder with accumulation of multipotent, megakaryocytic and erythroid progenitor cells and a mild impairment of differentiation along the granulocytic-monocytic lineage. Furthermore, BM cells from Cebpa(S248A/S248A) animals display a competitive advantage compared to wild type cells in a transplantation assay. CONCLUSIONS/SIGNIFICANCE: Taken together, our data shows that the substitution of C/EBPα serine 248 to alanine favors the selection of the megakaryocytic/erythroid lineage over the monocytic/granulocytic compartment in old mice and suggests that S248 phosphorylation may be required to maintain proper hematopoietic homeostasis in response to changes in the wiring of cellular signalling networks. More broadly, the marked differences between the phenotype of the S248A variant in vivo and in vitro highlight the need to exert caution when extending in vitro phenotypes to the more appropriate in vivo context

Pathways and Management of Phosphorus in urban areas

Due to the finite nature of mineral phosphorus reserves, effective management of anthropogenic phosphorus flows is currently under investigation by the international research community. This article emphasizes the importance of urban phosphorus flows, which are often marginalized due to the greater magnitude of agricultural phosphorus flows. A study on phosphorus flows in Gothenburg, Sweden, points out the potential role of solid waste in nutrient management, as the amounts of phosphorus in solid waste and in wastewater were found to be equal. Importation of food commodities accounts for 50% of the total inflow of phosphorus, and food waste is a major contributor of phosphorus to solid waste. The results suggest that solid waste incineration residues represent a large underestimated sink of phosphorus. Focusing on wastewater as the sole source of recovered phosphorus is not sufficient. The Swedish national goal on phosphorus recycling, which is limited to sewage sludge, targets only a part of the total phosphorus flow that can potentially be recovered. In contrast to previous studies, agricultural flows in Gothenburg were marginal compared to flows related to the urban waste management infrastructure. We emphasize the need for debate on preferable routes for disposal of waste with a high phosphorus content. Both recovery potential and usefulness of the recovered product for agricultural purposes have to be considered. Impacts of five waste management strategies on phosphorus flows were evaluated: incineration of all the waste, comprehensive food waste separation, installation of kitchen grinders, urine diversion, and separation of blackwater and food waste

Mutant CEBPA directly drives the expression of the targetable tumor-promoting factor CD73 in AML

The key myeloid transcription factor (TF), CEBPA, is frequently mutated in acute myeloid leukemia (AML), but the direct molecular effects of this leukemic driver mutation remain elusive. To investigate mutant AML, we performed microscale, in vivo chromatin immunoprecipitation sequencing and identified a set of aberrantly activated enhancers, exclusively occupied by the leukemia-associated CEBPA-p30 isoform. Comparing gene expression changes in human mutant AML and the corresponding mouse model, we identified , encoding CD73, as a cross-species AML gene with an upstream leukemic enhancer physically and functionally linked to the gene. Increased expression of CD73, mediated by the CEBPA-p30 isoform, sustained leukemic growth via the CD73/A2AR axis. Notably, targeting of this pathway enhanced survival of AML-transplanted mice. Our data thus indicate a first-in-class link between a cancer driver mutation in a TF and a druggable, direct transcriptional target

Summary Report on CO{sub 2} Geologic Sequestration & Water Resources Workshop

The United States Environmental Protection Agency (EPA) and Lawrence Berkeley National Laboratory (LBNL) jointly hosted a workshop on “CO{sub 2} Geologic Sequestration and Water Resources” in Berkeley, June 1–2, 2011. The focus of the workshop was to evaluate R&D needs related to geological storage of CO{sub 2} and potential impacts on water resources. The objectives were to assess the current status of R&D, to identify key knowledge gaps, and to define specific research areas with relevance to EPA’s mission. About 70 experts from EPA, the DOE National Laboratories, industry, and academia came to Berkeley for two days of intensive discussions. Participants were split into four breakout session groups organized around the following themes: Water Quality and Impact Assessment/Risk Prediction; Modeling and Mapping of Area of Potential Impact; Monitoring and Mitigation; Wells as Leakage Pathways. In each breakout group, participants identified and addressed several key science issues. All groups developed lists of specific research needs; some groups prioritized them, others developed short-term vs. long-term recommendations for research directions. Several crosscutting issues came up. Most participants agreed that the risk of CO{sub 2} leakage from sequestration sites that are properly selected and monitored is expected to be low. However, it also became clear that more work needs to be done to be able to predict and detect potential environmental impacts of CO{sub 2} storage in cases where the storage formation may not provide for perfect containment and leakage of CO{sub 2}–brine might occur

Global shortage of technical agars: back to basics (resource management)

Bacteriological and technical agars are in short supply with potential consequences for research, public health, and clinical labs around the world. To diagnose bottlenecks and sustainability problems that may be putting the industry at risk, we analyzed the available time series for the global landings of Gelidium, the most important raw materials for the industry. Data on the harvest of Gelidium spp. have been reported since1912, when Japan was the only producer. After World War II the diversification of harvested species and producing countries resulted in a strong increase in global landings. Maximum harvest yields of almost 60,000 t year(-1) in the 1960s were sustained until the 1980s, after which landings decreased continuously to the present. In the 2010s, a reduction in the global production to about 25,000 t year(-1) was observed, which was lower than the yields of the 1950s. Landings by important producers such as Japan, Korea, Spain, and Portugal have collapsed. This is the ultimate cause of the present shortage of bacteriological and technical agars. However, an important factor at play is the concentration of the global landings of Gelidium in Morocco, as its relative contribution increased from 23% in the 1960s to the present 82%. Two specific bottlenecks were identified: restrictive export quotas of unprocessed Gelidium in favor of the national agar industry and resource management regulations that were apparently not enforced resulting in over-harvesting and resource decline. The global industry may well be dependent on resource management basics. Simple harvest statistics must be gathered such as the harvest effort and the variation of harvest yields along the harvest season. We discuss how this information is fundamental to manage the resource. The available harvest statistics are generally poor and limited and vary significantly among different sources of data. Probable confusions between dry and wet weight reporting and poor discrimination of the species harvested need to be resolved

Genetic plasticity of the Shigella virulence plasmid is mediated by intra- and inter-molecular events between insertion sequences

Acquisition of a single copy, large virulence plasmid, pINV, led to the emergence of Shigella spp. from Escherichia coli. The plasmid encodes a Type III secretion system (T3SS) on a 30kb pathogenicity island (PAI), and is maintained in a bacterial population through a series of toxin:antitoxin (TA) systems which mediate post-segrega tional killing (PSK). The T3SS imposes a significant cost on the bacterium, and strains which have lost the plasmid and/or genes encoding the T3SS grow faster than wild-type strains in the laboratory, and fail to bind the indicator dye Congo Red (CR). Our aim was to define the molecular events in Shigella flexneri that cause loss of Type III secretion (T3S), and to examine whether TA systems exert positional effects on pINV. During growth at 37°C, we found that deletions of regions of the plasmid including the PAI lead to the emergence of CR-negative colonies; deletions occur through intra-molecula r recombination events between insertion sequences (ISs) flanking the PAI. Furthermore, by repositioning MvpAT (which belongs to the VapBC family of TA systems) near the PAI, we demonstrate that the location of this TA system alters the rearrangements that lead to loss of T3S, indicating that MvpAT acts both globally (by reducing loss of pINV through PSK) as well as locally (by preventing loss of adjacent sequences). During growth at environmental temperatures, we show for the first time that pINV spontaneously integrates into different sites in the chromosome, and this is mediated by inter-molecular events involving IS 1294. Integration leads to reduced PAI gene expression and impaired secretion through the T3SS, while excision of pINV from the chromosome restores T3SS function. Therefore, pINV integration provides a reversible mechanism for Shigella to circumvent the metabolic burden imposed by pINV. Intra- and inter-molecular events between ISs, which are abundant in Shigella spp., mediate plasticity of S. flexneri pINV

The Eco-Epidemiology of Pacific Coast Tick Fever in California

Rickettsia philipii (type strain “Rickettsia 364D”), the etiologic agent of Pacific Coast tick fever (PCTF), is transmitted to people by the Pacific Coast tick, Dermacentor occidentalis. Following the first confirmed human case of PCTF in 2008, 13 additional human cases have been reported in California, more than half of which were pediatric cases. The most common features of PCTF are the presence of at least one necrotic lesion known as an eschar (100%), fever (85%), and headache (79%); four case-patients required hospitalization and four had multiple eschars. Findings presented here implicate the nymphal or larval stages of D. occidentalis as the primary vectors of R. philipii to people. Peak transmission risk from ticks to people occurs in late summer. Rickettsia philipii DNA was detected in D. occidentalis ticks from 15 of 37 California counties. Similarly, non-pathogenic Rickettsia rhipicephali DNA was detected in D. occidentalis in 29 of 38 counties with an average prevalence of 12.0% in adult ticks. In total, 5,601 ticks tested from 2009 through 2015 yielded an overall R. philipii infection prevalence of 2.1% in adults, 0.9% in nymphs and a minimum infection prevalence of 0.4% in larval pools. Although most human cases of PCTF have been reported from northern California, acarological surveillance suggests that R. philipii may occur throughout the distribution range of D. occidentalis