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At least 541 records · Page 30

Modulation of adhesion-dependent cAMP signaling by echistatin and alendronate

We measured intracellular cAMP levels in cells during attachment and spreading on different extracellular matrix (ECM) proteins. Increases in cAMP were observed within minutes when cells attached to fibronectin, vitronectin, and a synthetic RGD-containing fibronectin peptide (Petite 2000), but not when they adhered to another integrin alpha nu beta 3 ligand, echistatin. Because echistatin also inhibits bone resorption, we measured the effects of adding another osteoporosis inhibitor, alendronate, in this system. Alendronate inhibited the cAMP increase induced by ligands that primarily utilize integrin alpha nu beta 3 (vitronectin, Peptite 2000), but not by fibronectin which can also use integrin alpha 5 beta 1. These results show that cell adhesion to ECM can increase intracellular cAPM levels and raise the possibility that inhibitors of osteoporosis may act, in part, by preventing activation of this pathway by integrins.

NASA Discipline Number 40-20↗

Subtask 1.3 – Integrated Carbon Capture and Storage for North Dakota Ethanol Production

Presentation for Mastering the Subsurface Through Technology Innovation, Partnerships and Collaboration: Carbon Storage and Oil and Natural Gas Technologies Review Meeting, Pittsburgh, Pennsylvania, August 13–16, 2018. The goal of this project is to implement a small‑scale (<200,000 metric tons of CO₂ per year) commercial carbon capture and storage (CCS) system at an industrial fuel production facility to produce reduced‑carbon ethanol eligible for low‑carbon fuel programs. Objectives include developing a framework for CCS deployment at small facilities, evaluating the full carbon life cycle of fuel production with CCS, and assessing the viability of CCS pathways for meeting Low Carbon Fuel Standard (LCFS) requirements. The project also seeks to validate the Broom Creek Formation, an aeolian reservoir, as a viable regional geologic storage target for CO 2 .

09 BIOMASS FUELS↗

Vision Changes after Space Flight Are Related to Alterations in Folate-Dependent One-Carbon Metabolism

About 20% of astronauts on International Space Station missions have developed measurable ophthalmic changes after flight. This study was conducted to determine whether the folate-dependent 1-carbon pathway is altered in these individuals. Data were modeled to evaluate differences between individuals with ophthalmic changes (n=5) and those without them (n=15). We also correlated mean preflight serum concentrations of the 1-carbon metabolites with changes in measured refraction after flight. Serum homocysteine (HCy), cystathionine, 2-methylcitric acid, and methylmalonic acid concentrations were 25%-45% higher (P<0.001) in astronauts with ophthalmic changes than in those without them. These differences existed before, during, and after flight. Preflight serum HCy and cystathionine, and in-flight serum folate, were significantly (P<0.05) correlated with postflight change in refraction, and preflight serum concentrations of 2-methylcitric acid tended to be associated (P=0.06) with ophthalmic changes. The biochemical differences observed in those with vision issues strongly suggests impairment of the folate-dependent 1-carbon transfer pathway. Impairment of this pathway, by polymorphisms, diet or other means, may interact with components of the microgravity environment to influence these pathophysiologic changes. This study was funded by the NASA Human Research Program.

Smith, Scott M.↗

Reinforcement Learning for Generating Toolpaths in Additive Manufacturing

Generating toolpaths plays a key role in additive manufacturing processes. In the case of 3-Dimensional (3D) printing, these toolpaths are the pathways the printhead will follow to fabricate a part in a layer-by-layer fashion. Most toolpath generators use nearest neighbor (NN), branch-and-bound, or linear programming algorithms to produce valid toolpaths. These algorithms often produce sub-optimal results or cannot handle large sets of traveling points. In this paper, the researchers at Oak Ridge National Laboratory’s (ORNL) Manufacturing Demonstration Facility (MDF) propose using a machine learning (ML) approach called reinforcement learning (RL) to produce toolpaths for a print. RL is the process of two agents, the player and the critic, learning how to maximize a score based upon the actions of the player in a defined state space. In the context of 3D printing, the player will learn how to find the optimal toolpath that reduces printhead lifts and global print time.

Patrick, Steven↗

From PeleC to PeleACC, to PeleC++

PeleC is an Exascale Computing Project application for simulating compressible combustion in complex geometries. It has been built on top of the popular AMReX library. In the beginning of the Exascale Computing Project, PeleC was focused on KNL. It uses a mixture of C++, C, and kernels written in Fortran to obtain performance by focusing on vectorization. Recently we have taken two approaches in deciding PeleC's future for obtaining performance on exascale GPU machines. In the first programming model, we decorated the Fortran kernels with OpenACC directives. This expedited our ability to run at large scales on Summit's GPUs, where we achieved a significant speedup over the CPUs on Summit. The second programming model involved rewriting the Fortran kernels in C++ and using AMReX's Kokkos-like lambda abstractions for running on the GPU. This resulted in similar speedups on Summit's GPUs over merely utilizing the CPUs. Both approaches involved AMReX's management of memory transfers between the device and host. In this work, we compare and contrast the benefits and pitfalls to both programming approaches regarding performance, performance portability, and productivity. We also discuss advantages we have found in taking the time to modernize our code and why have chosen a specific pathway to prepare our code for the future DOE exascale machines.

exascale computing↗

The Pathway to a Safe and Effective Medication Formulary for Exploration Spaceflight

PURPOSE: Exploration space missions pose several challenges to providing a comprehensive medication formulary designed to accommodate the size and space limitations of the spacecraft; while addressing the individual medications needs and preferences of the Crew; the negative outcome of a degrading inventory over time, the inability to resupply before expiration dates; and the need to properly forecast the best possible medication candidates to treat conditions that will occur in the future. METHODS: The Pharmacotherapeutics Discipline has partnered with the Exploration Medical Capabilities (ExMC) Element to develop and propose a research pathway that is comprehensively focused on evidence-based models and theories, as well as on new diagnostic tools and treatments or preventive measures aimed at closure of the Med02 “Pharmacy” Gap; defined in the Human Research Program’s (HRP) risk-based research strategy. The Med02 Gap promotes the challenge to identify a strategy to ensure that medications used to treat medical conditions during exploration space missions are available, safe, and effective. It is abundantly clear that pharmaceutical intervention is an essential component of risk management planning for astronaut healthcare during exploration space. However, the quandary still remains of how to assemble a formulary that is comprehensive enough to prevent or treat anticipated medical events; and is also chemically stable, safe, and robust enough to have sufficient potency to last for the duration of an exploration space mission. In cases where that is not possible, addressing this Gap requires exploration of novel drug development techniques, dosage forms, and dosage delivery platforms that enhance chemical stability as well as therapeutic effectiveness. RESULTS: The proposed research pathway outlines the steps, processes, procedures, and a research portfolio aimed at identifying a capability that will provide a safe and effective pharmacy for any specific exploration Design Reference Mission (DRM). The proposed approach to building this research portfolio is to seek research projects that concentrate on four major focus areas; (1) Formulary selection, (2) Formulary potency and shelf life, (3) Formulary safety and toxicity, and (4) Novel technology and innovation such as portable real-time chemical analysis innovative drug therapies and dosage and delivery platforms. CONCLUSION: The research pathway has been completed and presented to the HRP. In spring 2017, it is scheduled to be reviewed by a panel of pharmaceutical and clinical experts that will evaluate the scientific merit and operational feasibility of the research pathway, as well as make suggestions for any warranted additions or improvements. Once finalized, the ExMC Element will proceed with the execution of this research pathway with the goal of gathering as much data, and learning as much as possible, to provide a safe and effective pharmaceutical formulary for use during exploration missions.

Daniels, V. R.↗

Regional and Sexual Dimorphism in Murine Skeletal Responses to Osteocytic HIF Pathway Modulation

Hypoxia-inducible factors (HIFs) are transcription factors stabilized under hypoxia and degraded under normoxia by the E3 ubiquitin ligase Von Hippel-Lindau (Vhl). In osteocytes, the central orchestrators of bone homeostasis, Vhl and HIFs promote an osteoanabolic transcriptional program. In this study, we assessed unique impacts of osteocytic Vhl deletion versus individual HIF-α paralog stabilization on bone structure, mineralization, and mechanics as a function of sex and skeletal region. Microcomputed tomography revealed that osteocytic Vhl deletion robustly increased trabecular bone mass in both sexes and at both axial and appendicular regions, while HIF-2α accumulation increased femoral metaphyseal bone mass in both sexes while enhancing vertebral bone mass only in males. Vhl deletion paradoxically reduced mineral heterogeneity in male vertebrae, despite raising peak and mean calcium content in both sexes. In contrast, HIF-2α stabilization impaired cortical mineralization and mechanics, especially in females. While cortical mineralization was disrupted in both genotypes, Vhl deletion improved whole bone mechanical properties, suggesting that enhanced geometry and mass offset compromised tissue quality. HIF-1α stabilization exerted negligible impacts on any outcome.

Biological and medical sciences↗

Lunar COTS: Using the Moon's Resources to Enable An Economical and Sustainable Pathway to Mars and Beyond

To support NASAs goal of sending humans to Mars, a new plan was constructed to develop and demonstrate cislunar capabilities and services in partnership with commercial industry using the well-proven Commercial Orbital Transportation Services (COTS) Program acquisition model. The NASA COTS Program was a very successful program that developed and demonstrated cost-effective commercial cargo transportation services to the International Space Station (ISS). As a result of NASAs COTS program, two new launch vehicles and spacecraft were developed and have been successfully performing cargo transportation missions to the ISS since 2012. The COTS acquisition strategy utilized a new model than normally accepted in traditional procurement practices. This new model used Space Act Agreements where NASA entered into partnerships with industry to jointly share cost, development and operational risks to demonstrate new capabilities for mutual benefit. This model proved to be very beneficial to both NASA and its industry partners as NASA saved significantly in development and operational costs, as much as tenfold, while industry partners successfully expanded their market share of the global launch transportation business for significant economic benefit. Using the COTS acquisition model as a basis, a new plan, notionally referred to as Lunar Commercial Orbital Transfer Services (or Lunar COTS), has been developed to determine the potential benefits and challenges of a new Lunar COTS plan[1]. The proposed plan includes low-cost, commercial-enabled missions to prospect for resources, determine the economic viability of extracting those resources and assess the value proposition of using these resources in future exploration architectures such as Mars. These missions would be accomplished in partnership with industry to meet these exploration goals but will also have the capability to carry payloads to meet science goals as well.

Zuniga, Allison↗

Overview of Clean Hydrogen Program at NREL

Comprehensive, concerted efforts supported by the U.S. Department of Energy (DOE), Office of Energy Efficiency and Renewable Energy (EERE), Hydrogen and Fuel Cell Technologies Office (HFTO) are advancing research and development to demonstrate clean hydrogen production and industrial decarbonization pathways. These pathways enable an economically competitive and environmentally beneficial future energy system across sectors and can address specific applications that are difficult to decarbonize. NREL's research accelerates development, integration, and scale up of hydrogen and fuel cell technologies to enable widespread deployment across multiple energy sectors. Our work helps industry overcome technical challenges and supports DOE's H2@Scale vision for clean hydrogen across multiple applications and economic sectors. We also bridge technologies with other research areas across the lab and through multiple DOE and national lab research initiatives, consortia, and collaborations including: the Hydrogen Energy Earthshot, H2@Scale, National Clean Hydrogen Strategy and Roadmap, H2NEW: Hydrogen from Next-generation Electrolyzers of Water Consortium, HydroGEN: Advanced Water Splitting Materials Consortium, HyMARC Hydrogen Materials Advanced Research Consortium.

ARIES↗

Subtask 1.3 – Integrated Carbon Capture and Storage for North Dakota Ethanol Production

The Energy & Environmental Research Center (EERC), in partnership with Red Trail Energy, LLC (RTE), a North Dakota ethanol producer; the North Dakota Industrial Commission (NDIC) Renewable Energy Program (REP); and the U.S. Department of Energy (DOE), conducted a feasibility and implementation study for a commercial carbon capture and storage (CCS) effort. This subtask provided technical support and developed recommended practices of how small-scale industrial CO2 emitters (<1,000,000 tonnes of CO2 emitted annually) may economically deploy CCS. The 64-million-gallon dry mill RTE ethanol facility, emitting an average 180,000 tonnes of CO2 annually, was the subject of the case study. The positive outcome of this research, which shows technical and economic potential for ethanol–CCS in North Dakota, has resulted in RTE acquiring an approved Permit to Drill on December 2, 2019, for a stratigraphic test well in early 2020, a necessary step toward a North Dakota CO2 Storage Facility Permit (SFP) for the RTE CCS effort. Outcomes include 1) validating the Broom Creek Formation as a regional target for CCS, 2) determining the full carbon life cycle of an industrial fuel production facility with CCS, 3) developing a field implementation plan (FIP) for small-scale CCS, and 4) determining the validity and pathway for using CCS to meet low-carbon fuel (LCF) standards. The technical team included the EERC, RTE, Trimeric Corporation, Schlumberger Carbon Services, and Computer Modelling Group (CMG). Findings from activities conducted November 2016 – May 2020 are summarized as follows. Several key steps have been accomplished toward validating the Broom Creek Formation as a CO2 injection and storage target at the RTE CCS site, including verification of the presence and structure of sandstone layers that may comprise the potential CO2 storage reservoir and the several thousand feet of overlying confining zone. Work included site characterization using existing data, interpretation of seismic data within the study area, and geologic modeling simulation of CO2 injection. Interpreted results estimate 3000 feet of confining zone between the Broom Creek Formation (storage target) and the lowermost underground source of drinking water (e.g., the Fox Hills Formation). The thickness of the Broom Creek injection target varies 230–420 ft within the survey area. Results were used to inform the location of a stratigraphic test well and associated characterization test program. No impediments were identified within the targeted CO2 storage complex that would prevent the project from moving forward. A stratigraphic test well is the next step to validate these results and to acquire remaining data necessary to develop a North Dakota CO2 SFP application. The EERC generated full carbon life cycle estimates for CCS integration with the RTE ethanol facility. Results indicated that an average 40% reduction in CO2 emissions is possible through CCS implementation. Approximately half of the carbon in the overall life cycle for a dry mill ethanol plant is generated through the fermentation process and emitted to the atmosphere; this is the CO2 stream targeted for CCS. The remaining carbon is attributed to corn feedstock farming (diesel, fertilizer), energy for fuel processing (natural gas, electricity), and transportation (diesel) of the fuel product. Life cycle carbon estimates are also affected by the anticipated energy consumption of a potential capture facility, which depend on the type of CO2 product generated. For example, a 30%–40% net CO2 emission reduction is estimated if a liquefied CO2 facility were incorporated compared to a 40%–50% net CO2 reduction if a supercritical “injection-grade” CO2 product is generated; i.e., more energy is required to further refine the CO2 stream, affecting the full carbon life cycle estimates. A CCS FIP was developed and initiated at the RTE CCS site, resulting in the development of several guidance documents: a CO2 Capture Process Design Package, a North Dakota CO2 geologic Storage Permits Template, and a Public Outreach Package for CCS in North Dakota. General FIP components include CO2 capture system, pipeline and well designs; monitoring, verification, and accounting (MVA) plans; geologic characterization and testing programs; and permitting and outreach plans. Vendor bids were also acquired for the CO2 liquefaction facility. Near-surface characterization (groundwater and soil gas sampling) and geologic characterization (seismic survey) were initiated to inform development of a UIC Class VI-compliant MVA plan compliant with a North Dakota CO2 SFP. Designs (well and geologic testing) were completed for a stratigraphic test well compliant with a North Dakota CO2 SFP. In addition, the outreach plan was executed, including community open houses, meetings with city/county/state officials, and development of public materials. Although other entities continued to mature incentive programs in 2019–2020, California and the Internal Revenue Service (IRS) currently provide the most advanced economic opportunities for CCS integrated with fuel production. The California Low-Carbon Fuel Standard (LCFS) adopted a CCS Protocol in January 2019, allowing submittal of a design-based pathway (DBP) application for an approved temporary (not certified) carbon intensity value for a fully engineered facility. An ethanol–CCS DBP application to the California LCFS Program (officially approved February 28, 2020) was developed to show that the RTE CCS effort meets LCFS requirements. The approved DBP provides confidence to advance the project and supports potential investments. Other entities continue to mature incentive programs. The IRS issued guidance in February 2020 that addresses the definition of beginning of construction and revenue procedure on partnerships for the Enhancement of Carbon Dioxide Sequestration Credit (a.k.a. Section 45Q) CCS tax credit program; the IRS anticipates issuing further guidance on issues such as secure geologic storage, utilization qualifications, and recapture of claimed credits. Maturing incentive programs coupled with workable permitting regulations provide confidence to advance CCS projects in North Dakota and support financial investment to proceed with designing, constructing, and implementing CCS projects at small-scale fuel production facilities. The largest hurdles for CCS implementation at small-scale industrial systems are often business/economic-related (i.e., not technical). Market uncertainty already exists for agriculture-based alternative fuels such as corn ethanol, for which production has increased by ~33%, and prices have correspondingly lowered since 2015. Passing the Section 45Q tax credit program improves economic feasibility for CCS but may require external investors for a small business to achieve maximum benefits. Public–private partnerships with NDIC and DOE have resulted in foundational technical and regulatory knowledge, growing stakeholder confidence, and a pathway to implementation that enables similar industrial CCS projects in the region to advance. This subtask was funded through the EERC–DOE Joint Program on Research and Development for Fossil Energy-Related Resources Cooperative Agreement No. DE-FE0024233. Nonfederal funding was provided by NDIC and RTE. The authors would also like to thank CMG, ESRI, IHS, Neuralog, and Schlumberger for allowing the use of their software packages in support of this work.

42 ENGINEERING↗

Feedstock Supply System Design and Economics for Conversion of Lignocellulosic Biomass to Hydrocarbon Fuels Conversion Pathway: Fast Pyrolysis and Hydrotreating Bio-Oil Pathway "The 2017 Design Case"

The U.S. Department of Energy promotes the production of liquid fuels from lignocellulosic biomass feedstocks by funding fundamental and applied research that advances the state of technology in biomass sustainable supply, logistics, conversion, and overall system sustainability. As part of its involvement in this program, Idaho National Laboratory (INL) investigates the feedstock logistics economics and sustainability of these fuels. Between 2000 and 2012, INL quantified and the economics and sustainability of moving biomass from the field or stand to the throat of the conversion process using conventional equipment and processes. All previous work to 2012 was designed to improve the efficiency and decrease costs under conventional supply systems. The 2012 programmatic target was to demonstrate a biomass logistics cost of $\$$55/dry Ton for woody biomass delivered to fast pyrolysis conversion facility. The goal was achieved by applying field and process demonstration unit-scale data from harvest, collection, storage, preprocessing, handling, and transportation operations into INL’s biomass logistics model.

09 BIOMASS FUELS↗

Phenotypically anchored transcriptomics across diverse agrichemicals reveals conserved pathways and unique gene expression signatures in zebrafish

Agrichemicals such as herbicides, fungicides, insecticides, and biocides are widely used in agriculture, yet some are associated with adverse effects in humans and the environment. While many of these chemicals have been extensively studied in vitro and are included in the EPA’s ToxCast program, comprehensive in vivo comparisons using RNA sequencing across structurally diverse agrichemicals, in a single screening platform, are lacking. In this study, we examined structurally diverse agrichemicals found in the U.S. Environmental Protection Agency’s (EPA) Toxcast Phase I and II library by statically exposing early life stage zebrafish at 6 h post fertilization (hpf) until 120 hpf at concentrations ranging from 0.25 to 100 µM. Morphological outcomes were assessed at 120 hpf across 10 endpoints, including yolk sac edema, craniofacial malformations, and axis abnormalities. Chemicals that produced robust concentration-response relationships were selected for transcriptomic profiling. For transcriptomic analysis, zebrafish were statically exposed to each chemical and sampled at 48 hpf, prior to the onset of morphological effects observed at 120 hpf. Differential expression analysis identified between 0 and 4,538 differentially expressed genes (DEGs) per chemical, with no clear correlation to morphological severity. Both DEG and co-expression network analyses revealed chemical-specific expression patterns that converged on shared biological pathways, including neurodevelopment and cytoskeletal organization. Key regulatory genes such as mylpfa and krt4 were identified within co-expression modules, suggesting their potential role in conserved toxicity mechanisms. Semantic similarity analysis of enriched gene ontology (GO) terms, when compared to existing datasets, highlighted gaps in the annotation of neurodevelopmental processes, indicating that some in vivo effects may not be fully captured by current curated resources. The results provide new insights into the modes of action of diverse agrichemicals and establish a framework for understanding how agrichemical structure relates to biological function in a vertebrate model.

agrichemical↗

Transcript profiling of plastid ferrochelatase two mutants reveals that chloroplast singlet oxygen signals lead to global changes in RNA profiles and are mediated by Plant U-Box 4

Abstract Background In response to environmental stresses, chloroplasts generate reactive oxygen species, including singlet oxygen ( 1 O 2 ), an excited state of oxygen that regulates chloroplast-to-nucleus (retrograde) signaling, chloroplast turnover, and programmed cell death (PCD). Yet, the central signaling mechanisms and downstream responses remain poorly understood. TheArabidopsis thaliana plastid ferrochelatase two(fc2) mutant conditionally accumulates 1 O 2 , and Plant U-Box 4 (PUB4), a cytoplasmic E3 ubiquitin ligase, is involved in propagating 1 O 2 signals for chloroplast turnover and cellular degradation. Thus, thefc2andfc2 pub4mutants are useful genetic tools to elucidate these signaling pathways. Previous studies have focused on the role of 1 O 2 in promoting cellular degradation infc2mutants, but its impact on retrograde signaling from mature chloroplasts (the major site of 1 O 2 production) is poorly understood. Results To gain mechanistic insights into 1 O 2 signaling pathways, we compared transcriptomes of adult wt,fc2, andfc2 pub4plants. The accumulation of 1 O 2 infc2plants broadly repressed genes involved in chloroplast function and photosynthesis, while inducing genes and transcription factors involved in abiotic and biotic stress, the biosynthesis of jasmonic acid (JA) and salicylic acid (SA), microautophagy, and senescence. Elevated JA and SA levels were observed in 1 O 2 -stressedfc2plants.pub4reversed most of this 1 O 2 -induced gene expression and reduced the JA content infc2plants. Thepub4mutation also blocked JA-induced senescence pathways in the dark. However, fc2 pub4 plantsmaintained constitutively elevated levels of SA even in the absence of bulk 1 O 2 accumulation. Conclusions Together, this work demonstrates that infc2plants, 1 O 2 leads to a robust retrograde signal that may protect cells by downregulating photosynthesis and ROS production while simultaneously mounting a stress response involving SA and JA. The induction of microautophagy and senescence pathways indicate that 1 O 2 -induced cellular degradation is a genetic response to this stress, and the bulk of this transcriptional response is modulated by the PUB4 protein. However, the effect ofpub4on hormone synthesis and signaling is complex and indicates that an intricate interplay of SA and JA are involved in promoting stress responses and programmed cell death during photo-oxidative damage.

Plant Sciences↗

Estimation of Future PM2.5- and Ozone-related Mortality over the Continental United States in a Changing Climate: An application of High-resolution Dynamical Downscaling Technique

This paper evaluates the PM2.5- and ozone-related mortality at present (2000s) and in the future (2050s) over the continental United States by using the Environmental Benefits Mapping and Analysis Program (BenMAP-CE). Atmospheric chemical fields are simulated by WRF/CMAQ (horizontal resolution: 12 × 12km), applying the dynamical downscaling technique from global climate-chemistry models under the Representative Concentration Pathways scenario (RCP 8.5). Future air quality results predict that the annual mean PM2.5 concentrations in continental US will decrease nationwide, especially in the eastern US and west coast. However, the ozone concentration is projected to decrease in the Eastern US but increase in the Western US. Future mortality is evaluated under two scenarios (1) holding future population and baseline incidence rate at the present level and (2) decreasing the future baseline incidence rate but increasing the future population. For PM2.5, the entire continental US presents a decreasing trend of PM2.5-related mortality by the 2050s in Scenario (1), primarily resulting from the emissions reduction. While in Scenario (2), almost half of the continental states show a rising tendency of PM2.5-related mortality, due to the dominant influence of population growth. In particular, the highest PM2.5-related deaths and the biggest discrepancy between present and future PM2.5-related deaths will both occur in California in 2050s. For the ozone-related premature mortality, the simulation shows nation-wide rising tendency in 2050s under both two scenarios, mainly due to the increase of ozone concentration and population in the future. Furthermore, the uncertainty analysis shows that the effect of the all causes mortality is much larger than for specific causes. This assessment is the result of the accumulated uncertainty of generating datasets. The uncertainty range of ozone-related all cause premature mortality is narrower than the PM2.5-related all cause mortality, due to its smaller standard deviation of beta parameter.

BenMAP-CE↗

Cdc48a AAA‐ATPase and its association with ubiquitin‐like SAMP1 and DNA repair in Archaea

Cdc48/p97/VCP is an AAA ATPase, conserved in eukaryotes and archaea, which is demonstrated to convert chemical energy from the hydrolysis of ATP into the mechanical energy, for either unfolding protein substrates or dislodging protein substrates from complexes. The role of Cdc48 in ubiquitin mediated protein degradation has been well reported; however, its role in DNA repair is less understood so far. Evidence in eukaryotes which implicates Cdc48 in DNA repair is based on the association of Cdc48 with partners and substrate proteins, which are known to be involved in DNA damage response. In our study, we found Cdc48A of Haloferax volcanii co‐purifies with RecJ‐domain (RecJ3 and RecJ4) and RNase J1 homologs in an apparent thiol sensitive complex that binds the oxidative stress‐responsive, ubiquitin‐like SAMP1 in the presence of ATP . RecJ domain proteins are DNases reported to be involved in DNA repair pathways in bacteria. Further analysis revealed an Hfx. volcanii Δcdc48A mutant showed significant difference in survival when compared to its wildtype, on subjecting them to DNA damaging agents like phleomycin and UV. An increase (up to 3.4‐fold; p < 0.05) in transcript levels of cdc48a , recj3 and rnj1 was observed after treatment with the DNA damaging agent phleomycin, suggesting the expression of these genes is correlated with DNA repair. Current focus of this study is to decipher the role of Cdc48A in DNA repair by identifying its partner and substrate proteins. In addition, we are determining the substrate modifications required for signaling the Cdc48A mediated repair pathway using classic biochemistry techniques and genetic manipulations. Support or Funding Information The work was supported by funds awarded to Dr. Julie A. Maupin‐Furlow through the Bilateral NSF/BIO‐BBSRC program (NSF 1642283), U.S. Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences, Physical Biosciences Program (DOE DE‐FG02‐05ER15650) and the National Institutes of Health (NIH R01 GM57498). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Dantuluri, Swathi↗

U.S. Government Supports Low Emission Economic Growth (Fact Sheet)

Countries around the world face the challenge of maintaining long-term sustainable economic growth and development under the threat of climate change. By identifying and pursuing a sustainable development pathway now, they are better positioned to reach their economic growth goals while addressing climate change impacts and lowering greenhouse gas (GHG) emissions. Low emission development strategies - development plans that promote sustainable social and economic development while reducing long-term GHG emissions - provide a pathway to preparing for a global low emission future. Partner country governments are working with the U.S. government through the Enhancing Capacity for Low Emission Development Strategies (EC-LEDS) program to further their national development objectives.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

A calcium-dependent protein kinase can inhibit a calmodulin-stimulated Ca2+ pump (ACA2) located in the endoplasmic reticulum of Arabidopsis

The magnitude and duration of a cytosolic Ca(2+) release can potentially be altered by changing the rate of Ca(2+) efflux. In plant cells, Ca(2+) efflux from the cytoplasm is mediated by H(+)/Ca(2+)-antiporters and two types of Ca(2+)-ATPases. ACA2 was recently identified as a calmodulin-regulated Ca(2+)-pump located in the endoplasmic reticulum. Here, we show that phosphorylation of its N-terminal regulatory domain by a Ca(2+)-dependent protein kinase (CDPK isoform CPK1), inhibits both basal activity ( approximately 10%) and calmodulin stimulation ( approximately 75%), as shown by Ca(2+)-transport assays with recombinant enzyme expressed in yeast. A CDPK phosphorylation site was mapped to Ser(45) near a calmodulin binding site, using a fusion protein containing the N-terminal domain as an in vitro substrate for a recombinant CPK1. In a full-length enzyme, an Ala substitution for Ser(45) (S45/A) completely blocked the observed CDPK inhibition of both basal and calmodulin-stimulated activities. An Asp substitution (S45/D) mimicked phosphoinhibition, indicating that a negative charge at this position is sufficient to account for phosphoinhibition. Interestingly, prior binding of calmodulin blocked phosphorylation. This suggests that, once ACA2 binds calmodulin, its activation state becomes resistant to phosphoinhibition. These results support the hypothesis that ACA2 activity is regulated as the balance between the initial kinetics of calmodulin stimulation and CDPK inhibition, providing an example in plants for a potential point of crosstalk between two different Ca(2+)-signaling pathways.

NASA Discipline Plant Biology↗

U.S. Government Supports Low Emission Economic Growth

Countries around the world face the challenge of maintaining long-term sustainable economic growth and development under the threat of climate change. By identifying and pursuing a sustainable development pathway now, they are better positioned to reach their economic growth goals while addressing climate change impacts and lowering greenhouse gas (GHG) emissions. Low emission development strategies - development plans that promote sustainable social and economic development while reducing long-term GHG emissions - provide a pathway to preparing for a global low emission future. Partner country governments are working with the U.S. government through the Enhancing Capacity for Low Emission Development Strategies (EC-LEDS) program to further their national development objectives.

14 SOLAR ENERGY↗