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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 199 records · Page 11
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Models for Incorporating Equity in Transportation Electrification Considerations for Public Utility Regulators, An addendum to the NARUC report, Electric Vehicles: Key Trends, Issues, and Considerations for State Regulators (2019)

Momentum for the electric vehicle (EV) transition is well underway, and the utility sector plays an important role in supporting its success. For frontline communities, the transition offers a promising solution to improve environmental and public health outcomes, economic development, affordability, and transit equity. However, the transition will need to involve care and intention to ensure that the needs of underserved communities are prioritized throughout the planning, decision-making, and implementation processes. States have taken the lead in some cases, as profiled in Box 6. Whether driven by state commissions or utilities themselves, utilities have a range of options available to ensure equity is central in their transportation electrification plans and programs by drawing from a variety of existing and emerging experiences, as summarized in Table 1.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2017

Incentive-Based Voltage Regulation in Distribution Networks

This paper considers distribution networks fea- turing distributed energy resources, and designs incentive-based mechanisms that allow the network operator and end-customers to pursue given operational and economic objectives, while concurrently ensuring that voltages are within prescribed limits. Two different network-customer coordination mechanisms that require different amounts of information shared between the network operator and end-customers are developed to identify a solution of a well-defined social-welfare maximization prob- lem. Notably, the signals broadcast by the network operator assume the connotation of prices/incentives that induce the end- customers to adjust the generated/consumed powers in order to avoid the violation of the voltage constraints. Stability of the proposed schemes is analytically established and numerically corroborated.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2026

MassIVE MSV000100641 - Multilayered regulation by RNA thermometers enables precise control of Cas9 expression in E. coli: Cas9-based genome editing technologies can rapidly generate mutations to probe a diverse array of mutant genotypes. However, aberrant Cas9 nuclease translation and activity can occur despite the use of inducible promoters to control expression, leading to extensive cell death. This background killing caused by promoter leakiness severely limits the application of Cas9 for generating mutant libraries because of the potential for population skew. We demonstrate the utility of temperature sensitive RNA elements as a layer of post-transcriptional regulation to reduce the impact of promoter leak. We observe significant temperature-dependent increases in cell survival when certain RNA thermometers (RNATs) are placed upstream of the cas9 coding sequence. We also show that the most highly repressing RNAT, hsp17rep, significantly reduces population skew with a library of characterized guide RNAs in Escherichia coli. This strategy should be applicable to all bacterial Cas9-based methods and technologies.

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Alexander, William G. [Oak Ridge National Laborato↗
DOE OSTI2017

How the First Stars Regulated Star Formation. II. Enrichment by Nearby Supernovae

Metals from Population III (Pop III) supernovae led to the formation of less massive Pop II stars in the early universe, altering the course of evolution of primeval galaxies and cosmological reionization. There are a variety of scenarios in which heavy elements from the first supernovae were taken up into second-generation stars, but cosmological simulations only model them on the largest scales. We present small-scale, high-resolution simulations of the chemical enrichment of a primordial halo by a nearby supernova after partial evaporation by the progenitor star. We find that ejecta from the explosion crash into and mix violently with ablative flows driven off the halo by the star, creating dense, enriched clumps capable of collapsing into Pop II stars. Metals may mix less efficiently with the partially exposed core of the halo, so it might form either Pop III or Pop II stars. Both Pop II and III stars may thus form after the collision if the ejecta do not strip all the gas from the halo. The partial evaporation of the halo prior to the explosion is crucial to its later enrichment by the supernova.

79 ASTRONOMY AND ASTROPHYSICS↗
NASA NTRS1977

Effect of altered gravity on temperature regulation in mammals: Investigation of gravity effect on temperature regulation in mammals

Male, Long-Evans hooded rats were instrumented for monitoring core and hypothalamic temperatures as well as shivering and nonshivering thermogenesis in response to decreased ambient temperature in order to characterize the nature of the neural controller of temperature in rats at 1G and evaluate chronic implantation techniques for the monitoring of appropriate parameters at hypergravic fields. The thermoregulatory responses of cold-exposed rats at 2G were compared to those at 1G. A computer model was developed to simulate the thermoregulatory system in the rat. Observations at 1 and 2G were extended to acceleration fields of 1.5, 3.0 and 4.0G and the computer model was modified for application to altered gravity conditions. Changes in the acceleration field resulted in inadequate heat generation rather than increased heat loss. Acceleration appears to impair the ability of the neurocontroller to appropriately integrate input signals for body temperature maintenance.

Horwitz, B. A.↗
NASA NTRS1994

Experiment K-7-22: Growth Hormone Regulation Synthesis and Secretion in Microgravity: Growth Hormone Regulation Synthesis and Secretion in Microgravity - Part 1

Changes in the musculoskeletal, immune, vascular, and endocrine system of the rat occur as a result of short-term spaceflight. Since pituitary gland growth hormone (GH) plays a role in the control of these systems, and since the results of an earlier spaceflight mission (Spacelab 3, 1985) showed that GH cell function was compromised in a number of post-flight tests, we repeated and extended the 1985 experiment in two subsequent spaceflights: the 12.5 day mission of Cosmos 1887 (in 1987) and the 14 day mission of Cosmos 2044 (in 1989). The results of these later two flight experiments are the subject of this report. They document repeatable and significant changes in the GH cell system of the spaceflown rat in several post-flight tests.

Hymer, W. C.↗
DOE OSTI2020

Francisella novicida Two-Component System Response Regulator BfpR Modulates iglC Gene Expression, Antimicrobial Peptide Resistance, and Biofilm Production

Response regulators are a critical part of the two-component system of gene expression regulation in bacteria, transferring a signal from a sensor kinase into DNA binding activity resulting in alteration of gene expression. In this study, we investigated a previously uncharacterized response regulator in Francisella novicida, FTN_1452 that we have named BfpR (Biofilm-regulating Francisella protein Regulator, FTN_1452). In contrast to another Francisella response regulator, QseB/PmrA, BfpR appears to be a negative regulator of biofilm production, and also a positive regulator of antimicrobial peptide resistance in this bacterium. The protein was crystallized and X-ray crystallography studies produced a 1.8 Å structure of the BfpR N-terminal receiver domain revealing interesting insight into its potential interaction with the sensor kinase. Structural analysis of BfpR places it in the OmpR/PhoP family of bacterial response regulators along with WalR and ResD. Proteomic and transcriptomic analyses suggest that BfpR overexpression affects expression of the critical Francisella virulence factor iglC, as well as other proteins in the bacterium. We demonstrate that mutation of bfpR is associated with an antimicrobial peptide resistance phenotype, a phenotype also associated with other response regulators, for the human cathelicidin peptide LL-37 and a sheep antimicrobial peptide SMAP-29. F. novicida with mutated bfpR replicated better than WT in intracellular infection assays in human-derived macrophages suggesting that the down-regulation of iglC expression in bfpR mutant may enable this intracellular replication to occur. Response regulators have been shown to play important roles in the regulation of bacterial biofilm production. We demonstrate that F. novicida biofilm formation was highly increased in the bfpR mutant, corresponding to altered glycogen synthesis. Waxworm infection experiments suggest a role of BfpR as a negative modulator of iglC expression with de-repression by Mg 2+ . In this study, we find that the response regulator BfpR may be a negative regulator of biofilm formation, and a positive regulator of antimicrobial peptide resistance in F. novicida.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2005

Series-Connected Buck Boost Regulators

A series-connected buck boost regulator (SCBBR) is an electronic circuit that bucks a power-supply voltage to a lower regulated value or boosts it to a higher regulated value. The concept of the SCBBR is a generalization of the concept of the SCBR, which was reported in "Series-Connected Boost Regulators" (LEW-15918), NASA Tech Briefs, Vol. 23, No. 7 (July 1997), page 42. Relative to prior DC-voltage-regulator concepts, the SCBBR concept can yield significant reductions in weight and increases in power-conversion efficiency in many applications in which input/output voltage ratios are relatively small and isolation is not required, as solar-array regulation or battery charging with DC-bus regulation. Usually, a DC voltage regulator is designed to include a DC-to-DC converter to reduce its power loss, size, and weight. Advances in components, increases in operating frequencies, and improved circuit topologies have led to continual increases in efficiency and/or decreases in the sizes and weights of DC voltage regulators. The primary source of inefficiency in the DC-to-DC converter portion of a voltage regulator is the conduction loss and, especially at high frequencies, the switching loss. Although improved components and topology can reduce the switching loss, the reduction is limited by the fact that the converter generally switches all the power being regulated. Like the SCBR concept, the SCBBR concept involves a circuit configuration in which only a fraction of the power is switched, so that the switching loss is reduced by an amount that is largely independent of the specific components and circuit topology used. In an SCBBR, the amount of power switched by the DC-to-DC converter is only the amount needed to make up the difference between the input and output bus voltage. The remaining majority of the power passes through the converter without being switched. The weight and power loss of a DC-to-DC converter are determined primarily by the amount of power processed. In the SCBBR, the unswitched majority of the power is passed through with very little power loss, and little if any increase in the sizes of the converter components is needed to enable the components to handle the unswitched power. As a result, the power-conversion efficiency of the regulator can be very high, as shown in the example of Figure 1. A basic SCBBR includes a DC-to-DC converter (see Figure 2). The switches and primary winding of a transformer in the converter is connected across the input bus, while the secondary winding and switches are connected in series with the output bus, so that the output voltage is the sum of the input voltage and the secondary voltage of the converter. In the breadboard SCBBR, the input voltage applied to the primary winding is switched by use of metal oxide/semiconductor field-effect transistors (MOSFETs) in a full bridge circuit; the secondary winding is center-tapped, with two MOSFET switches and diode rectifiers connected in opposed series in each leg. The sets of opposed switches and rectifiers are what enable operation in either a boost or a buck mode. In the boost mode, input voltage and current, and the output voltage and current are all positive; that is, the secondary voltage is added to the input voltage and the net output voltage can be regulated at a value equal or greater than the input voltage. In the buck mode, input voltage is still positive and the current still flows in the same direction in the secondary, but the switches are controlled such that some power flows from the secondary to the primary. The voltage across the secondary and the current into the primary are reversed. The result is that the output voltage is lower than the input voltage, and some power is recirculated from the converter secondary back to the input. Quantitatively, the advantage of an SCBBR is a direct function of the regulation range required. If, for example, a regulation range of 20 percent is required for a 500-W supply, th it suffices to design the DC-to-DC converter in the SCBBR for a power rating of only 100 W. The switching loss and size are much smaller than those of a conventional regulator that must be rated for switching of all 500 W. The reduction in size and the increase in efficiency are not directly proportional to switched-power ratio of 5:1 because the additional switches contribute some conduction loss and the input and output filters must be larger than those typically required for a 100-W converter. Nevertheless, the power loss and the size can be much smaller than those of a 500-W converter.

Birchenough, Arthur G.↗
DOE OSTI2016

miR-140-5p regulates hypoxia-mediated human pulmonary artery smooth muscle cell proliferation, apoptosis and differentiation by targeting Dnmt1 and promoting SOD2 expression

miR-140-5p is down-regulated in patients with pulmonary arterial hypertension (PAH) and experimental models of PAH, and inhibits hypoxia-mediated pulmonary artery smooth muscle cell (PASMC) proliferation in vitro. Delivery of synthetic miR-140-5p prevents and treats established, experimental PAH. DNA methyltransferase 1 (Dnmt1) is up-regulated in PAH associated human PASMCs (HPASMCs), which promotes the development of PAH by hypermethylation of CpG islands within the promoter for superoxide dismutase 2 (SOD2) and down-regulating SOD2 expression. We searched for miR-140-5p targets using TargetScan, PicTar and MiRanda tools, and found that Dnmt1 is a potential target of miR-140-5p. Based on these findings, we speculated that miR-140-5p might target Dnmt1 and regulate SOD2 expression to regulate hypoxia-mediated HPASMC proliferation, apoptosis and differentiation. We detected the expression of miR-140-5p, Dnmt1 and SOD2 by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays, respectively, and found down-regulation of miR-140-5p and SOD2 and up-regulation of Dnmt1 exist in PAH tissues and hypoxia-mediated HPASMCs. Cell proliferation, apoptosis and differentiation detection showed that miR-140-5p inhibits proliferation and promotes apoptosis and differentiation of HPASMCs in hypoxia, while the effect of Dnmt1 on hypoxia-mediated HPASMCs is reversed. Luciferase assay confirmed that miR-140-5p targets Dnmt1 directly. An inverse correlation is also found between miR-140-5p and Dnmt1 in HPASMCs. In addition, we further investigated whether miR-140-5p and Dnmt1 regulate HPASMC proliferation, apoptosis and differentiation by regulating SOD2 expression, and the results confirmed our speculation. Taken together, these results indicated that miR-140-5p at least partly targets Dnmt1 and regulates SOD2 expression to inhibit proliferation and promote apoptosis and differentiation of HPASMCs in hypoxia. - Highlights: • miR-140-5p and SOD2 are down-regulated in PAH tissues and hypoxia-mediated HPASMCs. • Dnmt1 is up-regulated in PAH tissues and hypoxia-mediated HPASMCs. • miR-140-5p regulates HPASMC proliferation, apoptosis and differentiation. • Dnmt1 and SOD2 regulates HPASMC proliferation, apoptosis and differentiation. • miR-140-5p targets Dnmt1 and regulates SOD2 expression.

60 APPLIED LIFE SCIENCES↗
NASA NTRSDate not supplied

Space Suit Portable Life Support System Oxygen Regulator History, Development, & Testing Results

An oxygen regulator has been in development for the space suit Exploration Extravehicular Mobility Unit (xEMU) Portable Life Support System (PLSS). The regulator provides the necessary oxygen pressure for the crew member during pre-breathe, extra-vehicular activity (EVA), post EVA airlock operations, and decompression sickness treatment. The last time a spacesuit oxygen regulator was designed was for the Space Shuttle Program EMU. The regulator & EMU were then used on the International Space Station (ISS) with no significant changes to the regulator throughout its life. This xEMU PLSS spacesuit oxygen regulator implements many elements of the previous EMU Secondary Oxygen Pack (SOP) design while integrating numerous new improvements and changes. There are changes both to the high-level regulator architecture approach in the suit itself, in addition to modernizations with electrical motor control & sensing. For architecture, there are two oxygen regulators for each space suit, a primary and secondary that are nearly identical to each other and have the same maximum design pressure of 3750 Pounds per Square Inch Absolute (PSIA). The primary regulator provides nominal pressure during EVA, while the secondary provides a backup pressure only in case of primary regulator failure or if an emergency purge of the suit oxygen is required. The design was based originally off of the secondary oxygen regulator on the EMU which utilizes a two-stage regulator to improve safety and controllability. The xEMU PLSS Oxygen Regulator development started with a modification to add a linear actuator to the design to control the downstream pressure electronically instead of a manual control with a wire linkage system used with the EMU. The design was iterated to include a Monel body for oxygen fire safety, and sensors for pressure verification at each stage. Then the regulator design was packaged to fit into the xEMU PLSS envelope. Development included extensive testing which brought to light some issues with the design which were addressed at each stage of development. This paper will review the design history, development, testing results, and lessons learned designing the xEMU PLSS Oxygen Regulator.

Ryan Ogilvie↗
DOE OSTI2020

Assessments of data centers for provision of frequency regulation

There are numerous opportunities for data centers to participate in demand response programs considering their large energy capacities, flexible working environments and workloads, redundant design and operation, etc. As a type of demand response, frequency regulation requires fast response, and its potential is not fully explored by data centers yet. This paper proposes a synergistic control strategy for data center frequency regulation which uses both IT and cooling systems. It combines power management techniques at the server level with control of the chilled water supply temperature to track the regulation signal from the electrical market. A frequency regulation flexibility factor is also proposed to increase the IT capacity for frequency regulation. The performance of the control strategy is studied through numerical simulations using an equation based object-oriented Modelica platform designed for data centers. Simulation results show that with well-tuned control parameters, data centers can provide frequency regulation service in both regulation up and down. The performance of data centers in providing frequency regulation service is largely influenced by the regulation capacity bid, frequency regulation flexibility factor, workload condition, and cooling mode of the cooling system, and not significantly influenced by the time constant of chillers. In addition, compared with a server-only control strategy, the proposed synergistic control strategy can provide an extra regulation capacity of 3% of the design power when chillers are activated. Here, when chillers are deactivated, both strategies have a similar regulation capacity.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2016

miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis in osteosarcoma cells

miR-130b was significantly up-regulated in osteosarcoma (OS) cells. Naked cuticle homolog 2 (NKD2) inhibited tumor growth and metastasis in OS by suppressing Wnt signaling. We used three miRNA target analysis tools to identify potential targets of miR-130b, and found that NKD2 is a potential target of miR-130b. Based on these findings, we hypothesize that miR-130b might target NKD2 and regulate the Wnt signaling to promote OS growth. We detected the expression of miR-130b and NKD2 mRNA and protein by quantitative Real-Time PCR (qRT-PCR) and western blot assays, respectively, and found up-regulation of miR-130b and down-regulation of NKD2 mRNA and protein exist in OS cell lines. MTT and flow cytometry assays showed that miR-130b inhibitors inhibit proliferation and promote apoptosis in OS cells. Furthermore, we showed that NKD2 is a direct target of miR-130b, and miR-130b regulated proliferation and apoptosis of OS cells by targeting NKD2. We further investigated whether miR-130b and NKD2 regulate OS cell proliferation and apoptosis by inhibiting Wnt signaling, and the results confirmed our speculation that miR-130b targets NKD2 and regulates the Wnt signaling to promote proliferation and inhibit apoptosis of OS cells. These findings will offer new clues for OS development and progression, and novel potential therapeutic targets for OS. - Highlights: • miR-130b is up-regulated and NKD2 is down-regulated in osteosarcoma cell lines. • Down-regulation of miR-130b inhibits proliferation of osteosarcoma cells. • Down-regulation of miR-130b promotes apoptosis of osteosarcoma cells. • miR-130b directly targets NKD2. • NKD2 regulates OS cell proliferation and apoptosis by inhibiting the Wnt signaling.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2008

Bidirectional Pressure-Regulator System

A bidirectional pressure-regulator system has been devised for use in a regenerative fuel cell system. The bidirectional pressure-regulator acts as a back-pressure regulator as gas flows through the bidirectional pressure-regulator in one direction. Later, the flow of gas goes through the regulator in the opposite direction and the bidirectional pressure-regulator operates as a pressure- reducing pressure regulator. In the regenerative fuel cell system, there are two such bidirectional regulators, one for the hydrogen gas and another for the oxygen gas. The flow of gases goes from the regenerative fuel cell system to the gas storage tanks when energy is being stored, and reverses direction, flowing from the storage tanks to the regenerative fuel cell system when the stored energy is being withdrawn from the regenerative fuel cell system. Having a single bidirectional regulator replaces two unidirectional regulators, plumbing, and multiple valves needed to reverse the flow direction. The term "bidirectional" refers to both the bidirectional nature of the gas flows and capability of each pressure regulator to control the pressure on either its upstream or downstream side, regardless of the direction of flow.

Burke, Kenneth↗
DOE OSTI2020

A Systematic Evidence Based Performance Approach to Regulation of Nuclear Sites in England and Wales - 20058

The Environment Agency for England has developed a systematic evidence-based approach to pursue our strategic environmental objectives for the regulation of nuclear sites. We use an annual evidence review process to ensure effective and efficient targeting of limited resources to achieve those objectives. Over the last 8 years, we have been developing and refining this approach to ensure risk-based and value driven regulation. The approach comprises nuclear site and nuclear sector review processes known as Site Environment Review (SER) and Nuclear Environment Review (NER). This approach complements our regulation of nuclear site permit holders under the Environmental Permitting Regulations (EPR). We deliver our regulation of nuclear sites in England and Wales alongside the Office for Nuclear Regulation. The SER process involves the lead regulator for each nuclear site assessing the permit holder's environmental performance across 14 themes, set within the context of the site's main activities and associated waste disposals. Our themes include environmental leadership, resources and climate change, radioactive waste management, facility management and decommissioning, groundwater, and environmental radiological protection. We use evidence from site inspections and working within our subject matter groups to grade current and predicted future environmental performance. We are particularly interested in sustainability and the application of Best Available Techniques (BAT) to prevent the creation, and minimise the disposal, of radioactive wastes. We use risk analysis (strengths, weaknesses, threats and opportunities) to examine performance against our strategic environmental objectives, which are set out, in our 5-year Nuclear Delivery Plan (NDP). The output supports the targeting of our resources at each nuclear site. We consult the relevant permit holders on the SER priorities and use their feedback to refine our plans. We expect all permit holders to take account of our priorities when considering their own programmes of work, objectives and plans. The NER process brings together what we learn and achieve through regulation across the sector. It provides input to planning priorities, supported by qualitative and semi-quantitative evidence. It covers the 28 nuclear sites in England and Wales and spans the same 14 environmental themes. During the process we collate, compile and summarise evidence from the SERs and other sources such as inspection reports and evidence from our other nuclear work programmes. The output is the NER annual report. This provides a snapshot of the status of the nuclear sector and gives insights to enable us to regulate more efficiently and effectively. It also takes account of cross-cutting issues and risks such as changes in international standards, domestic policy, regulatory framework, domestic standards and guidance, learning from experience such as incidents, events and good practice, and innovation, research and development. It provides graphics that illustrate the grading of environmental performance for the nuclear sector across the fourteen environmental themes. This analysis allows benchmarking of nuclear site's environmental performance and the visualisation provides a convenient comparison of performance across themes, sites, and over time. We use this intelligence to inform our investment in training and development of our staff, and our cross-cutting engagement on strategic issues with government, the Nuclear Decommissioning Authority (NDA) and other corporate organisations. Adopting this approach can provide benefits with organisational reputation, stakeholder participation and ensuring value from the public investment. This paper describes the history of the SER/NER process, a selection of outputs from the process and ideas for improvement. The paper will be of interest to other regulators and organisations across the world that are interested in supporting continuous improvement. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
NASA NTRS1999

Coordinate up-regulation of low-density lipoprotein receptor and cyclo-oxygenase-2 gene expression in human colorectal cells and in colorectal adenocarcinoma biopsies

Many colorectal cancers have high levels of cyclo-oxygenase 2 (COX-2), an enzyme that metabolizes the essential fatty acids into prostaglandins. Since the low-density lipoprotein receptor (LDLr) is involved in the uptake of essential fatty acids, we studied the effect of LDL on growth and gene regulation in colorectal cancer cells. DiFi cells grown in lipoprotein-deficient sera (LPDS) grew more slowly than cells with LDL. LDLr antibody caused significant inhibition of tumor cell growth but did not affect controls. In addition, LDL uptake did not change in the presence of excess LDL, suggesting that ldlr mRNA lacks normal feedback regulation in some colorectal cancers. Analysis of the ldlr mRNA showed that excess LDL in the medium did not cause down-regulation of the message even after 24 hr. The second portion of the study examined the mRNA expression of ldlr and its co-regulation with cox-2 in normal and tumor specimens from patients with colorectal adenocarcinomas. The ratio of tumor:paired normal mucosa of mRNA expression of ldlr and of cox-2 was measured in specimens taken during colonoscopy. ldlr and cox-2 transcripts were apparent in 11 of 11 carcinomas. There was significant coordinate up-regulation both of ldlr and of cox-2 in 6 of 11 (55%) tumors compared with normal colonic mucosa. There was no up-regulation of cox-2 without concomitant up-regulation of ldlr. These data suggest that the LDLr is abnormally regulated in some colorectal tumors and may play a role in the up-regulation of cox-2. Copyright 1999 Wiley-Liss, Inc.

Non-NASA Center↗
DOE OSTI2013

Thyroid hormone negatively regulates CDX2 and SOAT2 mRNA expression via induction of miRNA-181d in hepatic cells

Highlights: •Thyroid hormone induces miR-181d expression in human hepatic cells and mouse livers. •Thyroid hormone downregulates CDX2 and SOAT2 (or ACAT2) via miR-181d. •miR-181d reduces cholesterol output from human hepatic cells. -- Abstract: Thyroid hormones (THs) regulate transcription of many metabolic genes in the liver through its nuclear receptors (TRs). Although the molecular mechanisms for positive regulation of hepatic genes by TH are well understood, much less is known about TH-mediated negative regulation. Recently, several nuclear hormone receptors were shown to downregulate gene expression via miRNAs. To further examine the potential role of miRNAs in TH-mediated negative regulation, we used a miRNA microarray to identify miRNAs that were directly regulated by TH in a human hepatic cell line. In our screen, we discovered that miRNA-181d is a novel hepatic miRNA that was regulated by TH in hepatic cell culture and in vivo. Furthermore, we identified and characterized two novel TH-regulated target genes that were downstream of miR-181d signaling: caudal type homeobox 2 (CDX2) and sterol O-acyltransferase 2 (SOAT2 or ACAT2). CDX2, a known positive regulator of hepatocyte differentiation, was regulated by miR-181d and directly activated SOAT2 gene expression. Since SOAT2 is an enzyme that generates cholesteryl esters that are packaged into lipoproteins, our results suggest miR-181d plays a significant role in the negative regulation of key metabolic genes by TH in the liver.

60 APPLIED LIFE SCIENCES↗