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At least 703 records · Page 39
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential

Significance Circadian clocks regulate gene expression levels to allow an organism to anticipate environmental conditions. These clocks reside in all the major branches of life and confer a competitive advantage to the organisms that maintain them. The clock in the fungus Neurospora crassa is an excellent model for basic understanding of core circadian architecture as well as for filamentous fungi. Here, we identify genes whose expression is clock regulated; indeed, as much as 40% of the transcriptome may be clock regulated, broadly directing daytime catabolism and nighttime growth. Both transcriptional control and posttranscriptional regulation play major roles in control of cycling transcripts such that DNA binding of transcription factors alone appears insufficient to set the phase of circadian transcription.

Hurley, Jennifer M.↗
DOE OSTI2017

LEC1 sequentially regulates the transcription of genes involved in diverse developmental processes during seed development

Significance Seed development is biphasic, consisting of the morphogenesis phase when the basic plant body plan is established and the maturation phase when the embryo accumulates storage reserves and becomes desiccation tolerant. Despite the importance of seeds as human food and animal feed, little is known about the gene-regulatory networks that operate during these phases. We identified genes that are regulated genetically and transcriptionally by a master regulator of seed development, LEAFY COTYLEDON1 (LEC1). We show that LEC1 transcriptionally regulates genes involved in photosynthesis and other developmental processes in early and maturation genes in late seed development. Our results suggest that LEC1 partners with different transcription factors to regulate distinct gene sets and that LEC1 function is conserved in Arabidopsis and soybean seed development.

Pelletier, Julie M.↗
DOE OSTI2021

DNA affinity purification sequencing and transcriptional profiling reveal new aspects of nitrogen regulation in a filamentous fungus

Significance Microorganisms have evolved transcriptional networks to prioritize utilization of available nutrient sources. For filamentous fungi, such as Neurospora crassa , this entails distinguishing between a variety of organic and inorganic nitrogen sources. Here, we transcriptionally profiled the response of N. crassa to a variety of nitrogen sources and used DNA affinity purification sequencing to characterize the role of regulatory genes and their direct downstream targets. We identified a transcription factor responsible for regulating genes involved in amino acid and mannose metabolism. By comparing the genes regulated by transcription factors that regulate specific nitrogen utilization pathways and transcription factors that regulate utilization of all nitrogen sources that require metabolic processing before utilization, we revealed aspects of the nitrogen regulatory network.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

DWARF GALAXY FORMATION WITH H{sub 2}-REGULATED STAR FORMATION

We describe cosmological galaxy formation simulations with the adaptive mesh refinement code Enzo that incorporate a star formation prescription regulated by the local abundance of molecular hydrogen. We show that this H{sub 2}-regulated prescription leads to a suppression of star formation in low-mass halos (M{sub h} {approx}< 10{sup 10} M{sub Sun }) at z > 4, alleviating some of the dwarf galaxy problems faced by theoretical galaxy formation models. H{sub 2} regulation modifies the efficiency of star formation of cold gas directly, rather than indirectly reducing the cold gas content with 'supernova feedback'. We determine the local H{sub 2} abundance in our most refined grid cells (76 proper parsec in size at z = 4) by applying the model of Krumholz, McKee, and Tumlinson, which is based on idealized one-dimensional radiative transfer calculations of H{sub 2} formation-dissociation balance in {approx}100 pc atomic-molecular complexes. Our H{sub 2}-regulated simulations are able to reproduce the empirical (albeit lower z) Kennicutt-Schmidt relation, including the low {Sigma}{sub gas} cutoff due to the transition from atomic to molecular phase and the metallicity dependence thereof, without the use of an explicit density threshold in our star formation prescription. We compare the evolution of the luminosity function, stellar mass density, and star formation rate density from our simulations to recent observational determinations of the same at z = 4-8 and find reasonable agreement between the two.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2013

THE KINETIC SUNYAEV-ZEL'DOVICH EFFECT AS A PROBE OF THE PHYSICS OF COSMIC REIONIZATION: THE EFFECT OF SELF-REGULATED REIONIZATION

We calculate the angular power spectrum of the cosmic microwave background temperature fluctuations induced by the kinetic Sunyaev-Zel'dovich (kSZ) effect from the epoch of reionization (EOR). We use detailed N-body+radiative-transfer simulations to follow inhomogeneous reionization of the intergalactic medium. For the first time, we take into account the ''self-regulation'' of reionization: star formation in low-mass dwarf galaxies (10{sup 8} M{sub Sun} {approx}< M {approx}< 10{sup 9} M{sub Sun }) or minihalos (10{sup 5} M{sub Sun} {approx}< M {approx}< 10{sup 8} M{sub Sun }) is suppressed if these halos form in the regions that were already ionized or Lyman-Werner dissociated. Some previous work suggested that the amplitude of the kSZ power spectrum from the EOR can be described by a two-parameter family: the epoch of half-ionization and the duration of reionization. However, we argue that this picture applies only to simple forms of the reionization history which are roughly symmetric about the half-ionization epoch. In self-regulated reionization, the universe begins to be ionized early, maintains a low level of ionization for an extended period, and then finishes reionization as soon as high-mass atomically cooling halos dominate. While inclusion of self-regulation affects the amplitude of the kSZ power spectrum only modestly ({approx}10%), it can change the duration of reionization by a factor of more than two. We conclude that the simple two-parameter family does not capture the effect of a physical, yet complex, reionization history caused by self-regulation. When added to the post-reionization kSZ contribution, our prediction for the total kSZ power spectrum is below the current upper bound from the South Pole Telescope. Therefore, the current upper bound on the kSZ effect from the EOR is consistent with our understanding of the physics of reionization.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2013

BLACK HOLE-GALAXY CORRELATIONS WITHOUT SELF-REGULATION

Recent models of black hole growth in a cosmological context have forwarded a paradigm in which the growth is self-regulated by feedback from the black hole itself. Here we use cosmological zoom simulations of galaxy formation down to z = 2 to show that such strong self-regulation is required in the popular spherical Bondi accretion model, but that a plausible alternative model in which black hole growth is limited by galaxy-scale torques does not require self-regulation. Instead, this torque-limited accretion model yields black holes and galaxies evolving on average along the observed scaling relations by relying only on a fixed, 5% mass retention rate onto the black hole from the radius at which the accretion flow is fed. Feedback from the black hole may (and likely does) occur, but does not need to couple to galaxy-scale gas in order to regulate black hole growth. We show that this result is insensitive to variations in the initial black hole mass, stellar feedback, or other implementation details. The torque-limited model allows for high accretion rates at very early epochs (unlike the Bondi case), which if viable can help explain the rapid early growth of black holes, while by z {approx} 2 it yields Eddington factors of {approx}1%-10%. This model also yields a less direct correspondence between major merger events and rapid phases of black hole growth. Instead, growth is more closely tied to cosmological disk feeding, which may help explain observational studies showing that, at least at z {approx}> 1, active galaxies do not preferentially show merger signatures.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2020

HEXIM1 controls P-TEFb processing and regulates drug sensitivity in triple-negative breast cancer

The positive transcription elongation factor b (P-TEFb), composed of CDK9 and cyclin T, stimulates transcriptional elongation by RNA polymerase (Pol) II and regulates cell growth and differentiation. Recently, we demonstrated that P-TEFb also controls the expression of EMT regulators to promote breast cancer progression. In the nucleus, more than half of P-TEFb are sequestered in the inactive-state 7SK snRNP complex. Here, we show that the assembly of the 7SK snRNP is preceded by an intermediate complex between HEXIM1 and P-TEFb that allows transfer of the kinase active P-TEFb from Hsp90 to 7SK snRNP for its suppression. Down-regulation of HEXIM1 locks P-TEFb in the Hsp90 complex, keeping it in the active state to enhance breast cancer progression, but also rendering the cells highly sensitive to Hsp90 inhibition. Because HEXIM1 is often down-regulated in human triple-negative breast cancer (TNBC), these cells are particularly sensitive to Hsp90 inhibition. Our study provides a mechanistic explanation for the increased sensitivity of TNBC to Hsp90 inhibition.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

cMonkey2: Automated, systematic, integrated detection of co-regulated gene modules for any organism

The cMonkey integrated biclustering algorithm identifies conditionally co-regulated modules of genes (biclusters). cMonkey integrates various orthogonal pieces of information which support evidence of gene co-regulation, and optimizes biclusters to be supported simultaneously by one or more of these prior constraints. The algorithm served as the cornerstone for constructing the first global, predictive Environmental Gene Regulatory Influence Network (EGRIN) model for a free-living cell, and has now been applied to many more organisms. However, due to its computational inefficiencies, long run-time and complexity of various input data types, cMonkey was not readily usable by the wider community. To address these primary concerns, we have significantly updated the cMonkey algorithm and refactored its implementation, improving its usability and extendibility. These improvements provide a fully functioning and user-friendly platform for building co-regulated gene modules and the tools necessary for their exploration and interpretation. We show, via three separate analyses of data for E. coli, M. tuberculosis and H. sapiens, that the updated algorithm and inclusion of novel scoring functions for new data types (e.g. ChIP-seq and transcription factor over-expression [TFOE]) improve discovery of biologically informative co-regulated modules. The complete cMonkey2 software package, including source code, is available at https://github.com/baliga-lab/cmonkey2.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulation

The catalytic activity of human cytidine deaminase APOBEC3B (A3B) has been correlated with kataegic mutational patterns within multiple cancer types. The molecular basis of how the N-terminal non-catalytic CD1 regulates the catalytic activity and consequently, biological function of A3B remains relatively unknown. Here, we report the crystal structure of a soluble human A3B-CD1 variant and delineate several structural elements of CD1 involved in molecular assembly, nucleic acid interactions and catalytic regulation of A3B. We show that (i) A3B expressed in human cells exists in hypoactive high-molecular-weight (HMW) complexes, which can be activated without apparent dissociation into low-molecular-weight (LMW) species after RNase A treatment. (ii) Multiple surface hydrophobic residues of CD1 mediate the HMW complex assembly and affect the catalytic activity, including one tryptophan residue W127 that likely acts through regulating nucleic acid binding. (iii) One of the highly positively charged surfaces on CD1 is involved in RNA-dependent attenuation of A3B catalysis. (iv) Surface hydrophobic residues of CD1 are involved in heterogeneous nuclear ribonucleoproteins (hnRNPs) binding to A3B. The structural and biochemical insights described here suggest that unique structural features on CD1 regulate the molecular assembly and catalytic activity of A3B through distinct mechanisms.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Modeling temporal and hormonal regulation of plant transcriptional response to wounding

Plants respond to wounding stress by changing gene expression patterns and inducing the production of hormones including jasmonic acid. This wounding transcriptional response activates specialized metabolism pathways such as the glucosinolate pathways in Arabidopsis thaliana. While the regulatory factors and sequences controlling a subset of wound-response genes are known, it remains unclear how wound response is regulated globally. Here, we how these responses are regulated by incorporating putative cis-regulatory elements, known transcription factor binding sites, in vitro DNA affinity purification sequencing, and DNase I hypersensitive sites to predict genes with different wound-response patterns using machine learning. We observed that regulatory sites and regions of open chromatin differed between genes upregulated at early and late wounding time-points as well as between genes induced by jasmonic acid and those not induced. Expanding on what we currently know, we identified cis-elements that improved model predictions of expression clusters over known binding sites. Using a combination of genome editing, in vitro DNA-binding assays, and transient expression assays using native and mutated cis-regulatory elements, we experimentally validated four of the predicted elements, three of which were not previously known to function in wound-response regulation. Our study provides a global model predictive of wound response and identifies new regulatory sequences important for wounding without requiring prior knowledge of the transcriptional regulators.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

A DE1 BINDING FACTOR 1–GLABRA2 module regulates rhamnogalacturonan I biosynthesis in Arabidopsis seed coat mucilage

Abstract The mucilage surrounding hydrated Arabidopsis thaliana seeds is a specialized extracellular matrix composed mainly of the pectic polysaccharide rhamnogalacturonan I (RG-I). Although, several genes responsible for RG-I biosynthesis have been identified, the transcriptional regulatory mechanisms controlling RG-I production remain largely unknown. Here we report that the trihelix transcription factor DE1 BINDING FACTOR 1 (DF1) is a key regulator of mucilage RG-I biosynthesis. RG-I biosynthesis is significantly reduced in loss-of-function mutants of DF1. DF1 physically interacts with GLABRA2 (GL2) and both proteins transcriptionally regulate the expression of the RG-I biosynthesis genes MUCILAGE MODIFIED 4 (MUM4) and GALACTURONOSYLTRANSFERASE-LIKE5 (GATL5). Through chromatin immunoprecipitation-quantitative PCR and transcriptional activation assays, we uncover a cooperative mechanism of the DF1–GL2 module in activating MUM4 and GATL5 expression, in which DF1 binds to the promoters of MUM4 and GATL5 through interacting with GL2 and facilitates the transcriptional activity of GL2. The expression of DF1 and GL2 is directly regulated by TRANSPARENT TESTA GLABRA2 (TTG2) and, in turn, DF1 directly represses the expression of TTG2. Taken together, our data reveal that the transcriptional regulation of mucilage RG-I biosynthesis involves a regulatory module, comprising DF1, GL2, and TTG2.

Biochemistry & Molecular Biology↗
DOE OSTI2025

PII interactions with the acetyl-CoA carboxylase subunits BADC and BCCP co-regulate lipid and nitrogen metabolism in Arabidopsis

In plants, the initiation of fatty acid synthesis is catalyzed by acetyl-CoA carboxylase (ACCase), which produces malonyl-CoA. The heteromeric form of ACCase (htACCase) is a holoenzyme consisting of biotin carboxylase and carboxyltransferase sub-complexes, both of which are subject to extensive regulation. Biotin carboxylase activity is controlled in part by the presence of the catalytic biotin carboxyl carrier proteins (BCCP1/2) and/or the non-catalytic, non-biotinylated, biotin/lipoyl attachment domain-containing proteins (BADC1/2/3) that associate with backbone biotin carboxylase (BC) protein. However, the mechanisms regulating BADC and BCCP interactions with BC and, consequently, ACCase activity in planta , remain unclear. Here, we demonstrate that the Arabidopsis ( Arabidopsis thaliana ) regulatory protein PII modulates htACCase activity through independent interactions with BADC and BCCP proteins in a selective manner. Analysis of badc1 badc2 and badc1 badc3 mutant lines and the respective pii triple mutants revealed that changes in seed oil and protein accumulation of badc double mutants are PII/nitrogen dependent. Absolute quantification of htACCase subunits and PII in developing seeds suggests that Arabidopsis exerts tight regulation over individual protein stoichiometry to balance oil and protein accumulation. The effects on vegetative and seed development indicate that PII and BADC proteins have distinct yet overlapping roles in regulating plant metabolism.

Garneau, Matthew G. [Washington State Univ., Pullm↗
DOE OSTI2014

Down-regulation of kelch domain-containing F-box protein in Arabidopsis enhances the production of (poly)phenols and tolerance to ultraviolet radiation

Phenylpropanoid biosynthesis in plants engenders myriad phenolics with diverse biological functions. Phenylalanine ammonia-lyase (PAL) is the first committed enzyme in the pathway, directing primary metabolic flux into a phenylpropanoid branch. Previously, we demonstrated that the Arabidopsis Kelch-domain containing F-box proteins, AtKFB01, -20, and -50, function as the negative regulators controlling phenylpropanoid biosynthesis via mediating PAL’s ubiquitination and subsequent degradation. Here, we reveal that Arabidopsis KFB39, a close homolog of AtKFB50, also interacts physically with PAL isozymes and modulates PALs' stability and activity. Disturbing the expression of KFB39 reciprocally affects the accumulation/deposition of a set of phenylpropanoid end products, suggesting that KFB39 is an additional post-translational regulator responsible for the turnover of PAL and negatively controlling phenylpropanoid biosynthesis. Furthermore, we discover that exposure of Arabidopsis to UV-B radiation suppresses the expression of all four KFB genes while inducing the transcription of PAL isogenes; these data suggest that Arabidopsis consolidates both transcriptional and post-translational regulation mechanisms to maximize its responses to UV stress. Simultaneous down-regulation of all four identified KFBs significantly enhances the production of (poly)phenols and the plant’s tolerance to UV irradiation. This study offers a biotechnological approach for engineering the production of useful phenolic chemicals and for increasing a plant’s resistance to environmental stress.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Cyber Physical Grid-Interactive Distributed Energy Resources Control for VPP Dispatch and Regulation

This paper presents a cyber-physical algorithm for grid-interactive Distributed Energy Resource (DER) control to enable two features of Virtual Power Plants (VPPs) dispatch and grid voltage regulation, considering the communication and security impacts. We first formulate the DER dispatch problem as a real-time, iterative, and grid-interactive DER control problem. Thereafter, we consider a probabilistic traffic model to characterize packet delays and loss in a communication network, and study how the delays enter the process of information exchange among the grid measurement units, local DER controllers and the grid control center that coordinately execute this dispatch algorithm. Finally, a strategy combining delay threshold and modified message update rules is proposed to immune the asynchrony resulting from the communications network traffic and it avoids possible numerical instabilities and sensitivities of the tracking and regulation capabilities of this DER control algorithm. By implementing the proposed cyber-physical algorithm on the modified IEEE 37-node system, our preliminary results exhibit that the uncertainties of the underlying communications infrastructure must be considered for the VPP tracking and regulation capabilities of any DER in a generic Cyber-Physical System (CPS), because the delayed voltage measurements in the uplink/bi-link cases result in the off-track in VPP dispatch and jittery in voltage regulation.

cyber-physical algorithm↗
DOE OSTI2021

Real-time Optimal Dispatch of Behind-the-Meter DERs for Secondary Frequency Regulation

Active distribution networks (ADNs) can provide grid services such as peak load shaving, loss reduction, VoltNar control, congestion management, and frequency regulation. The fast response of inverter-based distributed energy resources (DERs) and battery storage systems enables them to provide ramping support and frequency control. This paper proposes a real-time optimization approach for behind-the-meter DERs to participate in the secondary frequency regulation. The proposed approach determines optimal set-points of output power of DERs to respond to requests from system operators (SOs) in realtime to maintain the frequency of the system at the nominal value. To satisfy the real-time requirement for the secondary frequency control, the nonlinear AC power flow model is linearized considering power losses in the system to achieve both high computational speed and acceptable accuracy. The optimization problem is rerun in a closed loop manner until the mismatch between the requested power by the system operators and actual delivered power at the substation reaches an acceptable tolerance. Furthermore, the proposed approach is validated using modified versions of the IEEE 33-bus and IEEE 69-bus distribution systems. Although the contribution of a single distribution system in the frequency regulation may not be significant, stacked and coordinated contributions from several distribution systems can provide frequency regulation and other grid services at scale.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2021

A Cooperative Game Theory-based Secondary Frequency Regulation in Distribution Systems

Participation of distribution systems in frequency regulation has become an important factor for grid operation after the integration of distributed energy resources (DERs). While available reserves from a single distribution system may not be sufficient for frequency regulation, aggregated reserves from several distribution systems can provide frequency regulation at grid-scale. This paper proposes a cooperative game theory-based approach for secondary frequency regulation in distribution systems consisting of distributed energy resources (DERs). A two-stage strategy is proposed to effectively and precisely determine a change in active power set points of DERs following a command from system operators. In the first stage, the value or worth of each DER and their coalitions are determined using initial rates of change of frequency (ROCOF) for each DER/coalition. In the second stage, the Shapley value, one of the solution concepts of cooperative game theory, is used to determine changes in active power set points of DERs. The proposed method is implemented on several distribution systems including a modified IEEE 13-node system and modified 33-node distribution system.

Gautam, Mukesh↗
DOE OSTI2025

A Novel Secondary Frequency Regulation with Optimal Priority Selection of AGC Contributions

Automatic generation control (AGC) is used to maintain acceptable frequencies during operation owing to fluctuations in load and variable resources. In conventional industry applications, the AGC signal is allocated to each generator according to the predispatched frequency regulation capacity or the order of economic efficiency. However, with the increasing integration of inverter-based resources (IBRs), the retirement of conventional synchronous generators (SGs) has posed new challenges to frequency control schemes because fewer of them are optional for AGC regulation. In this paper, we propose a novel model predictive control (MPC)-based frequency regulation model to reduce control cost and ensure stability, by considering different critical dynamic factors when optimally selecting the AGC units. The proposed control model – developed in a general form – comprehensively embeds characteristics such as generator ramping rates, reserve capacity, and operation cost. The model predictive control–based two-timescale AGC scheme enhances the capability of immunizing the power disturbance from types of resources by coordinating the control signals between faster IBRs and slower SGs. The case study’s proposed model is verified to be effective in synergistically enforcing different dynamic properties of AGC units into the frequency regulation scheme.

Jiang, Sufan [The University of North Carolina at ↗
DOE OSTI2013

Prediction of Regulation Reserve Requirements in California ISO Control Area based on BAAL Standard

This paper presents new methodologies developed at Pacific Northwest National Laboratory (PNNL) to estimate regulation capacity requirements in the California ISO control area. Two approaches have been developed: (1) an approach based on statistical analysis of actual historical area control error (ACE) and regulation data, and (2) an approach based on balancing authority ACE limit control performance standard. The approaches predict regulation reserve requirements on a day-ahead basis including upward and downward requirements, for each operating hour of a day. California ISO data has been used to test the performance of the proposed algorithms. Results show that software tool allows saving up to 30% on the regulation procurements cost .

Etingov, Pavel V.↗