Architecture and modular assembly of Sulfolobus S-layers revealed by electron cryotomography.

Surface protein layers (S-layers) often form the only structural component of the archaeal cell wall and are therefore important for cell survival. S-layers have a plethora of cellular functions including maintenance of cell shape, osmotic, and mechanical stability, the formation of a semipermeable protective barrier around the cell, and cell-cell interaction, as well as surface adhesion. Despite the central importance of S-layers for archaeal life, their 3-dimensional (3D) architecture is still poorly understood. Here we present detailed 3D electron cryomicroscopy maps of archaeal S-layers from 3 different Sulfolobus strains. We were able to pinpoint the positions and determine the structure of the 2 subunits SlaA and SlaB. We also present a model describing the assembly of the mature S-layer.

Analyzing changes to U.S. municipal heat response plans during the COVID-19 pandemic.

Extreme heat events are the deadliest weather-related event in the United States. Cities throughout the United States have worked to develop heat adaptation strategies to limit the impact of extreme heat on vulnerable populations. However, the COVID-19 pandemic presented unprecedented challenges to local governments. This paper provides a preliminary review of strategies and interventions used to manage compound COVID-19-extreme heat events in the 25 most populous cities of the United States. Heat adaptation strategies employed prior to the COVID-19 pandemic were not adequate to meet during the co-occurring compound hazard of COVID-19-EHE. Long-term climate-adaptation strategies will require leveraging physical, financial, and community resources across multiple city departments to meet the needs of compound hazards, such as COVID-19 and extreme heat.

The structure and function of an RNA polymerase interaction domain in the PcrA/UvrD helicase.

The PcrA/UvrD helicase functions in multiple pathways that promote bacterial genome stability including the suppression of conflicts between replication and transcription and facilitating the repair of transcribed DNA. The reported ability of PcrA/UvrD to bind and backtrack RNA polymerase (1,2) might be relevant to these functions, but the structural basis for this activity is poorly understood. In this work, we define a minimal RNA polymerase interaction domain in PcrA, and report its crystal structure at 1.5 Å resolution. The domain adopts a Tudor-like fold that is similar to other RNA polymerase interaction domains, including that of the prototype transcription-repair coupling factor Mfd. Removal or mutation of the interaction domain reduces the ability of PcrA/UvrD to interact with and to remodel RNA polymerase complexes in vitro. The implications of this work for our understanding of the role of PcrA/UvrD at the interface of DNA replication, transcription and repair are discussed.

Costs and cost-effectiveness of malaria reactive case detection using loop-mediated isothermal amplification compared to microscopy in the low transmission setting of Aceh Province, Indonesia.

BACKGROUND: Reactive case detection (RACD) is an active case finding strategy where households and neighbours of a passively identified case (index case) are screened to identify and treat additional malaria infections with the goal of gathering surveillance information and potentially reducing further transmission. Although it is widely considered a key strategy in low burden settings, little is known about the costs and the cost-effectiveness of different diagnostic methods used for RACD. The aims of this study were to measure the cost of conducting RACD and compare the cost-effectiveness of microscopy to the more sensitive diagnostic method loop-mediated isothermal amplification (LAMP). METHODS: The study was conducted in RACD surveillance sites in five sub-districts in Aceh Besar, Indonesia. The cost inputs and yield of implementing RACD with microscopy and/or LAMP were collected prospectively over a 20 months study period between May 2014 and December 2015. Costs and cost-effectiveness (USD) of the different strategies were examined. The main cost measures were cost per RACD event, per person screened, per population at risk (PAR); defined as total population in each sub-district, and per infection found. The main cost-effectiveness measure was incremental cost-effectiveness ratio (ICER), expressed as cost per malaria infection detected by LAMP versus microscopy. The effects of varying test positivity rate or diagnostic yield on cost per infection identified and ICER were also assessed. RESULTS: Among 1495 household members and neighbours screened in 36 RACD events, two infections were detected by microscopy and confirmed by LAMP, and four infections were missed by microscopy but detected by LAMP. The average total cost of conducting RACD using microscopy and LAMP was $1178 per event with LAMP-specific consumables and personnel being the main cost drivers. The average cost of screening one individual during RACD was $11, with an additional cost of diagnostics at $0.62 and $16 per person for microscopy and LAMP, respectively. As a public health intervention, RACD using both diagnostics cost an average of $0.42 per PAR per year. Comparing RACD using microscopy only versus RACD using LAMP only, the cost per infection found was $8930 and $6915, respectively. To add LAMP as an additional intervention accompanying RACD would cost $9 per individual screened annually in this setting. The ICER was estimated to be $5907 per additional malaria infection detected by LAMP versus microscopy. Cost per infection identified and ICER declined with increasing test positivity rate and increasing diagnostic yield. CONCLUSIONS: This study provides the first estimates on the cost and cost-effectiveness of RACD from a low transmission setting. Costs per individual screened were high, though costs per PAR were low. Compared to microscopy, the use of LAMP in RACD was more costly but more cost-effective for the detection of infections, with diminishing returns observed when findings were extrapolated to scenarios with higher prevalence of infection using more sensitive diagnostics. As malaria programmes consider active case detection and the integration of more sensitive diagnostics, these findings may inform strategic and budgetary planning.

Water Use in the United States Energy System: A National Assessment and Unit Process Inventory of Water Consumption and Withdrawals.

The United States (US) energy system is a large water user, but the nature of that use is poorly understood. To support resource comanagement and fill this noted gap in the literature, this work presents detailed estimates for US-based water consumption and withdrawals for the US energy system as of 2014, including both intensity values and the first known estimate of total water consumption and withdrawal by the US energy system. We address 126 unit processes, many of which are new additions to the literature, differentiated among 17 fuel cycles, five life cycle stages, three water source categories, and four levels of water quality. Overall coverage is about 99% of commercially traded US primary energy consumption with detailed energy flows by unit process. Energy-related water consumption, or water removed from its source and not directly returned, accounts for about 10% of both total and freshwater US water consumption. Major consumers include biofuels (via irrigation), oil (via deep well injection, usually of nonfreshwater), and hydropower (via evaporation and seepage). The US energy system also accounts for about 40% of both total and freshwater US water withdrawals, i.e., water removed from its source regardless of fate. About 70% of withdrawals are associated with the once-through cooling systems of approximately 300 steam cycle power plants that produce about 25% of US electricity.

Spatially and Temporally Resolved Analysis of Environmental Trade-Offs in Electricity Generation.

The US power sector is a leading contributor of emissions that affect air quality and climate. It also requires a lot of water for cooling thermoelectric power plants. Although these impacts affect ecosystems and human health unevenly in space and time, there has been very little quantification of these environmental trade-offs on decision-relevant scales. This work quantifies hourly water consumption, emissions (i.e., carbon dioxide, nitrogen oxides, and sulfur oxides), and marginal heat rates for 252 electricity generating units (EGUs) in the Electric Reliability Council of Texas (ERCOT) region in 2011 using a unit commitment and dispatch model (UC&D). Annual, seasonal, and daily variations, as well as spatial variability are assessed. When normalized over the grid, hourly average emissions and water consumption intensities (i.e., output per MWh) are found to be highest when electricity demand is the lowest, as baseload EGUs tend to be the most water and emissions intensive. Results suggest that a large fraction of emissions and water consumption are caused by a small number of power plants, mainly baseload coal-fired generators. Replacing 8-10 existing power plants with modern natural gas combined cycle units would result in reductions of 19-29%, 51-55%, 60-62%, and 13-27% in CO2 emissions, NOx emissions, SOx emissions, and water consumption, respectively, across the ERCOT region for two different conversion scenarios.

Elevated O-GlcNAc levels activate epigenetically repressed genes and delay mouse ESC differentiation without affecting naïve to primed cell transition.

The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post-translational protein modifications. The addition of O-linked N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O-GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. Here, we demonstrate that the specific inhibition of O-GlcNAc hydrolase (Oga) causes increased levels of protein O-GlcNAcylation and impairs differentiation of mouse ESCs both in serum-free monolayer and in embryoid bodies (EBs). Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1-expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). In EBs, expression of mesodermal and endodermal markers is also delayed. However, the transition of naïve cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation remains unchanged. Finally, we demonstrate that increased O-GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation.

Critical review: Uncharted waters? The future of the electricity-water nexus.

Electricity generation often requires large amounts of water, most notably for cooling thermoelectric power generators and moving hydroelectric turbines. This so-called "electricity-water nexus" has received increasing attention in recent years by governments, nongovernmental organizations, industry, and academics, especially in light of increasing water stress in many regions around the world. Although many analyses have attempted to project the future water requirements of electricity generation, projections vary considerably due to differences in temporal and spatial boundaries, modeling frameworks, and scenario definitions. This manuscript is intended to provide a critical review of recent publications that address the future water requirements of electricity production and define the factors that will moderate the water requirements of the electric grid moving forward to inform future research. The five variables identified include changes in (1) fuel consumption patterns, (2) cooling technology preferences, (3) environmental regulations, (4) ambient climate conditions, and (5) electric grid characteristics. These five factors are analyzed to provide guidance for future research related to the electricity-water nexus.

Eliminating malaria in Malaysia: the role of partnerships between the public and commercial sectors in Sabah.

BACKGROUND: Countries in the Asia Pacific region have made great progress in the fight against malaria; several are rapidly approaching elimination. However, malaria control programmes operating in elimination settings face substantial challenges, particularly around mobile migrant populations, access to remote areas and the diversity of vectors with varying biting and breeding behaviours. These challenges can be addressed through subnational collaborations with commercial partners, such as mining or plantation companies, that can conduct or support malaria control activities to cover employees. Such partnerships can be a useful tool for accessing high-risk populations and supporting malaria elimination goals. METHODS: This observational qualitative case study employed semi-structured key informant interviews to describe partnerships between the Malaysian Malaria Control Programme (MCP), and private palm oil, rubber and acacia plantations in the state of Sabah. Semi-structured interview guides were used to examine resource commitments, incentives, challenges, and successes of the collaborations. RESULTS: Interviews with workers from private plantations and the state of Sabah MCP indicated that partnerships with the commercial sector had contributed to decreases in incidence at plantation sites since 1991. Several plantations contribute financial and human resources toward malaria control efforts and all plantations frequently communicate with the MCP to help monitor the malaria situation on-site. Management of partnerships between private corporations and government entities can be challenging, as prioritization of malaria control may change with annual profits or arrival of new management. CONCLUSIONS: Partnering with the commercial sector has been an essential operational strategy to support malaria elimination in Sabah. The successes of these partnerships rely on a common understanding that elimination will be a mutually beneficial outcome for employers and the general public. Best practices included consistent communication, developing government-staffed subsector offices for malaria control on-site, engaging commercial plantations to provide financial and human resources for malaria control activities, and the development of new worker screening programmes. The successes and challenges associated with partnerships between the public and commercial sector can serve as an example for other malaria-eliminating countries with large plantation sectors, and may also be applied to other sectors that employ migrant workers or have commercial enterprises in hard to reach areas.

The impact of water use fees on dispatching and water requirements for water-cooled power plants in Texas.

We utilize a unit commitment and dispatch model to estimate how water use fees on power generators would affect dispatching and water requirements by the power sector in the Electric Reliability Council of Texas' (ERCOT) electric grid. Fees ranging from 10 to 1000 USD per acre-foot were separately applied to water withdrawals and consumption. Fees were chosen to be comparable in cost to a range of water supply projects proposed in the Texas Water Development Board's State Water Plan to meet demand through 2050. We found that these fees can reduce water withdrawals and consumption for cooling thermoelectric power plants in ERCOT by as much as 75% and 23%, respectively. To achieve these water savings, wholesale electricity generation costs might increase as much as 120% based on 2011 fuel costs and generation characteristics. We estimate that water saved through these fees is not as cost-effective as conventional long-term water supply projects. However, the electric grid offers short-term flexibility that conventional water supply projects do not. Furthermore, this manuscript discusses conditions under which the grid could be effective at "supplying" water, particularly during emergency drought conditions, by changing its operational conditions.