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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 505 records · Page 28
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

Permeant calcium ion feed-through regulation of single inositol 1,4,5-trisphosphate receptor channel gating

The ubiquitous inositol 1,4,5-trisphosphate (InsP 3 ) receptor (InsP 3 R) Ca 2+ release channel plays a central role in the generation and modulation of intracellular Ca 2+ signals, and is intricately regulated by multiple mechanisms including cytoplasmic ligand (InsP 3 , free Ca 2+ , free ATP 4- ) binding, posttranslational modifications, and interactions with cytoplasmic and endoplasmic reticulum (ER) luminal proteins. However, regulation of InsP 3 R channel activity by free Ca 2+ in the ER lumen ([Ca 2+ ] ER ) remains poorly understood because of limitations of Ca 2+ flux measurements and imaging techniques. Here, we used nuclear patch-clamp experiments in excised luminal-side-out configuration with perfusion solution exchange to study the effects of [Ca 2+ ] ER on homotetrameric rat type 3 InsP 3 R channel activity. In optimal [Ca 2+ ] i and subsaturating [InsP 3 ], jumps of [Ca 2+ ] ER from 70 nM to 300 µM reduced channel activity significantly. This inhibition was abrogated by saturating InsP 3 but restored when [Ca 2+ ] ER was raised to 1.1 mM. In suboptimal [Ca 2+ ] i , jumps of [Ca 2+ ] ER (70 nM to 300 µM) enhanced channel activity. Thus, [Ca 2+ ] ER effects on channel activity exhibited a biphasic dependence on [Ca 2+ ] i . In addition, the effect of high [Ca 2+ ] ER was attenuated when a voltage was applied to oppose Ca 2+ flux through the channel. These observations can be accounted for by Ca 2 + flux driven through the open InsP 3 R channel by [Ca 2+ ] ER , raising local [Ca 2+ ] i around the channel to regulate its activity through its cytoplasmic regulatory Ca 2+ -binding sites. Importantly, [Ca 2+ ] ER regulation of InsP 3 R channel activity depended on cytoplasmic Ca 2+ -buffering conditions: it was more pronounced when [Ca2+] i was weakly buffered but completely abolished in strong Ca 2+ -buffering conditions. With strong cytoplasmic buffering and Ca 2+ flux sufficiently reduced by applied voltage, both activation and inhibition of InsP 3 R channel gating by physiological levels of [Ca 2+ ] ER were completely abolished. Collectively, these results rule out Ca 2+ regulation of channel activity by direct binding to the luminal aspect of the channel.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

DWARF GALAXY FORMATION WITH H{sub 2}-REGULATED STAR FORMATION. II. GAS-RICH DARK GALAXIES AT REDSHIFT 2.5

We present a cosmological hydrodynamic simulation of the formation of dwarf galaxies at redshifts z ∼> 2.5 using a physically motivated model for H{sub 2}-regulated star formation. Our simulation, performed using the Enzo code and reaching a peak resolution of 109 proper parsecs at z = 2.5, extends the results of Kuhlen et al. to significantly lower redshifts. We show that a star formation prescription regulated by the local H{sub 2} abundance leads to the suppression of star formation in dwarf galaxy halos with M{sub h} ∼< 10{sup 10} M{sub ☉} and to a large population of gas-rich 'dark galaxies' at z = 2.5 with low star formation efficiencies and gas depletion timescales >20 Gyr. The fraction of dark galaxies is 60% at M{sub h} ≅ 10{sup 10} M{sub ☉} and increases rapidly with decreasing halo mass. Dark galaxies form late and their gaseous disks never reach the surface densities, ∼> 5700 M{sub ☉} pc{sup –2} (Z/10{sup –3} Z{sub ☉}){sup –0.88}, that are required to build a substantial molecular fraction. Despite this large population of dark galaxies, we show that our H{sub 2}-regulated simulation is consistent with both the observed luminosity function of galaxies and the cosmological mass density of neutral gas at z ∼> 2.5. Moreover, our results provide a theoretical explanation for the recent detection in fluorescent Lyα emission of gaseous systems at high redshift with little or no associated star formation. We further propose that H{sub 2}-regulation may offer a fresh solution to a number of outstanding 'dwarf galaxy problems' in ΛCDM. In particular, H{sub 2}-regulation leads galaxy formation to become effectively stochastic on mass scales of M{sub h} ∼ 10{sup 10} M{sub ☉}, and thus these massive dwarfs are not 'too big to fail'.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2020

Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1

UHRF1 is an important epigenetic regulator associated with apoptosis and tumour development. It is a multidomain protein that integrates readout of different histone modification states and DNA methylation with enzymatic histone ubiquitylation activity. Emerging evidence indicates that the chromatin-binding and enzymatic modules of UHRF1 do not act in isolation but interplay in a coordinated and regulated manner. Here, we compared two splicing variants (V1, V2) of murine UHRF1 (mUHRF1) with human UHRF1 (hUHRF1). We show that insertion of nine amino acids in a linker region connecting the different TTD and PHD histone modification-binding domains causes distinct H3K9me3-binding behaviour of mUHRF1 V1. Structural analysis suggests that in mUHRF1 V1, in contrast to V2 and hUHRF1, the linker is anchored in a surface groove of the TTD domain, resulting in creation of a coupled TTD-PHD module. This establishes multivalent, synergistic H3-tail binding causing distinct cellular localization and enhanced H3K9me3-nucleosome ubiquitylation activity. In contrast to hUHRF1, H3K9me3-binding of the murine proteins is not allosterically regulated by phosphatidylinositol 5-phosphate that interacts with a separate less-conserved polybasic linker region of the protein. Our results highlight the importance of flexible linkers in regulating multidomain chromatin binding proteins and point to divergent evolution of their regulation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

A riboswitch separated from its ribosome-binding site still regulates translation

Abstract Riboswitches regulate downstream gene expression by binding cellular metabolites. Regulation of translation initiation by riboswitches is posited to occur by metabolite-mediated sequestration of the Shine-Dalgarno sequence (SDS), causing bypass by the ribosome. Recently, we solved a co-crystal structure of a prequeuosine1-sensing riboswitch from Carnobacterium antarcticum that binds two metabolites in a single pocket. The structure revealed that the second nucleotide within the gene-regulatory SDS, G34, engages in a crystal contact, obscuring the molecular basis of gene regulation. Here, we report a co-crystal structure wherein C10 pairs with G34. However, molecular dynamics simulations reveal quick dissolution of the pair, which fails to reform. Functional and chemical probing assays inside live bacterial cells corroborate the dispensability of the C10–G34 pair in gene regulation, leading to the hypothesis that the compact pseudoknot fold is sufficient for translation attenuation. Remarkably, the C. antarcticum aptamer retained significant gene-regulatory activity when uncoupled from the SDS using unstructured spacers up to 10 nucleotides away from the riboswitch—akin to steric-blocking employed by sRNAs. Accordingly, our work reveals that the RNA fold regulates translation without SDS sequestration, expanding known riboswitch-mediated gene-regulatory mechanisms. The results infer that riboswitches exist wherein the SDS is not embedded inside a stable fold.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Identification and functional analysis of strigolactone pathway genes regulating tillering traits in sugarcane

Abstract Saccharum officinarum and Saccharum spontaneum are two fundamental species of modern sugarcane cultivars, exhibiting divergent tillering patterns crucial for sugarcane architecture and yield. Strigolactones (SLs), a class of plant hormones, are considered to play a central role in shaping plant form and regulating tillering. Our study highlights the distinct tillering patterns observed between S. officinarum and S. spontaneum and implicates significant differences in SL levels in root exudates between the two species. Treatment with rac-GR24 (an artificial SL analog) suppressed tillering in S. spontaneum. Based on transcriptome analysis, we focused on two genes, TRANSCRIPTION ELONGATION FACTOR 1 (TEF1) and CIRCADIAN CLOCK ASSOCIATED1 (CCA1), which show higher expression in S. spontaneum or S. officinarum, respectively. While the overexpression of SoCCA1 did not lead to significant phenotypic differences, overexpression of SsTEF1 in rice stimulated tillering and inhibited plant height, demonstrating its role in tillering regulation. However, the overexpression of suggests that SoCCA1 may not be the key regulator of sugarcane tillering. Yeast one-hybrid assays identified four transcription factors (TFs) regulating SsTEF1 and four and five TFs regulating SsCCA1 and SoCCA1. This study provides a theoretical foundation for deciphering the molecular mechanisms underlying the different tillering behaviors between S. officinarum and S. spontaneum, providing valuable insights for the molecular-based design of sugarcane breeding strategies.

Qi, Yiying↗
DOE OSTI2024

Horocycle regulator: Exact cutoff-independence in AdS/CFT

While the entanglement entropy of a single subregion in quantum field theory is formally infinite and requires regularization, certain combinations of entropies are perfectly finite in the limit that the regulator is removed, the mutual information being a common example. For generic regulator schemes, such as a holographic calculation with a uniform radial cutoff, these quantities show nontrivial dependence on the regulator at finite values of the cutoff. We investigate a holographic regularization scheme defined in three-dimensional anti-de Sitter space constructed from , curves in two-dimensional hyperbolic space perpendicular to all geodesics approaching a single point on the boundary, that leads to finite information measures that are cutoff independent, even at finite values of the regulator. We describe a broad class of such information measures, and describe how the field theory dual to the horocycle regulator is inherently nonlocal. Published by the American Physical Society 2024

Agrawal, Sristy↗
DOE OSTI2022

Allocating Reserves in Active Distribution Systems for Tertiary Frequency Regulation

This paper proposes a cooperative game theory-based approach for reserve optimization to enable distributed energy resources (DERs) participate in tertiary frequency regulation. Tertiary frequency regulation schemes ensure that reserve requirements of primary and secondary frequency regulation are fulfilled with a minimum cost. While the available reserve from a single distribution system may not suffice tertiary frequency regulation, stacked reserve from several distribution systems can enable them participate in tertiary frequency regulation at scale. In this paper, a two-stage strategy is proposed to effectively and precisely allocate spinning reserve requirement from each DER in distribution systems. In the first stage, two types of characteristic functions are computed: worthiness index (WI) and power loss reduction (PLR). In the second stage, the equivalent Shapley values are computed based on the characteristic functions, which are used to determine distribution factors for reserve allocation among DERs. The effectiveness of the proposed method for allocating reserves among DERs is demonstrated through several case studies on modified versions of the IEEE 13-node and 33-node distribution systems.

Gautam, Mukesh↗
DOE OSTI2018

Improving BA Control Performance Through Advanced Regulation Requirements Prediction

The paper presents a comprehensive approach to predict balancing authority (BA) regulation requirements in order to improve BAs control performance. The proposed probabilistic approach takes into account multiple uncertain and time dependent factors affecting the system balance (e.g., wind and solar generation, electrical loads). A set of methods to predict the regulation has been developed: (1) probabilistic analysis of regulation requirements with respect to time of the day, (2) linear or nonlinear regression models linking regulation requirements to different influencing factors, (3) adopting time series forecasting techniques (e.g., autoregressive integrated moving average (ARIMA)) to account for temporal continuity and auto-correlation in the regulation requirements data. Proposed methodology has been tested and validated using actual California Independent System Operator (ISO) data.

Solar Generation, Wind Generation, Area Control Er↗
DOE OSTI2020

Muscone suppresses inflammatory responses and neuronal damage in a rat model of cervical spondylotic myelopathy by regulating Drp1‐dependent mitochondrial fission

Abstract Cervical spondylotic myelopathy (CSM) is a common cause of disability with few treatments. Aberrant mitochondrial dynamics play a crucial role in the pathogenesis of various neurodegenerative diseases. Thus, regulation of mitochondrial dynamics may offer therapeutic benefit for the treatment of CSM. Muscone, the active ingredient of an odoriferous animal product, exhibits anti‐inflammatory and neuroprotective effects for which the underlying mechanisms remain obscure. We hypothesized that muscone might ameliorate inflammatory responses and neuronal damage by regulating mitochondrial dynamics. To this end, the effects of muscone on a rat model of chronic cervical cord compression, as well as activated BV2 cells and injured neurons, were assessed. The results showed that muscone intervention improved motor function compared with vehicle‐treated rats. Indeed, muscone attenuated pro‐inflammatory cytokine expression, neuronal‐apoptosis indicators in the lesion area, and activation of the nod‐like receptor family pyrin domain‐containing 3 inflammasome, nuclear transcription factor‐κB, and dynamin‐related protein 1 in Iba1‐ and βIII‐tubulin‐labeled cells. Compared with vehicle‐treated rats, compression sites of muscone‐treated animals exhibited elongated mitochondrial morphologies in individual cell types and reduced reactive oxygen species. In vitro results indicated that muscone suppressed microglial activation and neuronal damage by regulating related‐inflammatory or apoptotic molecules. Moreover, muscone inhibited dynamin‐related protein 1 activation in activated BV2 cells and injured neurons, whereby it rescued mitochondrial fragmentation and reactive oxygen species production, which regulate a wide range of inflammatory and apoptotic molecules. Our findings reveal that muscone attenuates neuroinflammation and neuronal damage in rats with chronic cervical cord compression by regulating mitochondrial fission events, suggesting its promise for CSM therapy. image

Zhou, Long‐yun↗
DOE OSTI2018

The UzcRS two-component system in Caulobacter crescentus integrates regulatory input from diverse auxiliary regulators

The UzcRS two-component system in Caulobacter crescentus mediates widespread transcriptional activation in response to the metals U, Zn and Cu. Unexpectedly, a screen for mutations that affected the activity of the UzcR-regulated urcA promoter (P urcA ) revealed four previously uncharacterized proteins whose inactivation led to metal-independent induction of P urcA . Using molecular genetics and functional genomics, we find here that these auxiliary regulators control P urcA expression by modulating the activity of UzcRS through distinct mechanisms. An ABC transporter with a periplasmic metallo-aminopeptidase domain forms a sensory complex with UzcRS, antagonizing metal dependent stimulation by virtue of its ATPase and peptidase domains. Two MarR-like transcription factors synergistically regulate UzcRS activity by repressing the expression of the membrane proteins UzcY and UzcZ, which stimulate UzcRS activity and enhance its sensitivity to a more environmentally relevant U/Zn/Cu concentration range. Additionally, the membrane protein UzcX, whose expression is positively regulated by UzcR, provides a mechanism of feedback inhibition within the UzcRS circuit. Collectively, these data suggest that UzcRS functions as the core-signaling unit within a multicomponent signal transduction pathway that includes a diverse set of auxiliary regulators, providing further insight into the complexity of signaling networks.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Arabidopsis SnRK1 negatively regulates phenylpropanoid metabolism via Kelch domain-containing F-box proteins

Phenylpropanoid metabolism represents a substantial metabolic sink for the photosynthetically fixed carbon. The evolutionarily conserved Sucrose Non-Fermenting Related Kinase 1 (SnRK1) is a major metabolic sensor that reprograms metabolism upon carbon deprivation. However, it is not clear if and how SnRK1-mediated sugar signaling pathway controls phenylpropanoid metabolism. Here, we show that Arabidopsis SnRK1 negatively regulates phenylpropanoid biosynthesis via a group of Kelch domain-containing F-Box (KFB) proteins that are responsible for the ubiquitination and degradation of phenylalanine ammonia lyase (PAL). Down-regulation of AtSnRK1 significantly promoted the accumulation of soluble phenolics and lignin polymers and drastically increased PAL cellular accumulation but only slightly altered its transcription level. Co-expression of SnRK1α with PAL in Nicotiana benthamiana leaves resulted in the severe attenuation of the latter's protein level, but protein interaction assays suggested PAL is not a direct substrate of SnRK1. Furthermore, up- or down-regulation of AtSnRK1 positively affected KFB PALs gene expression, and energy starvation upregulated KFB PAL expression, which partially depends on AtSnRK1. Collectively, our study reveals that SnRK1 negatively regulates phenylpropanoid biosynthesis, and KFB PALs act as regulatory components of the SnRK1 signaling network, transcriptionally regulated by SnRK1 and subsequently mediating proteasomal degradation of PAL in response to the cellular carbon availability.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Cytokinin signaling localized in phloem noncell‐autonomously regulates cambial activity during secondary growth of Populus stems

Summary The regulation of cytokinin on secondary vascular development has been uncovered by modulating cytokinin content. However, it remains unclear how cytokinin enriched in developing secondary phloem regulates cambium activity in poplar. Here, we visualized the gradient distribution of cytokinin with a peak in the secondary phloem of poplar stem via immunohistochemical imaging, and determined the role of phloem‐located cytokinin signaling during wood formation. We generated transgenic poplar harboring cytokinin oxidase/dehydrogenase ( CKX)2 , a gene encoding a cytokinin degrading enzyme, driven by the phloem‐specific CLE41b promoter, indicating that the disruption of the cytokinin gradient pattern restricts the cambial activity. The RNA interference‐based knockdown of the histidine kinase ( HK ) genes encoding cytokinin receptors specifically in secondary phloem significantly compromised the division activity of cambial cells, whereas the phloem‐specific expression of a type‐B response regulator (RR) transcription factor stimulated cambial proliferation, providing evidence for the noncell‐autonomous regulation of local cytokinin signaling on the cambial activity. Moreover, the cambium‐specific knockdown of HK s also led to restricted cambial activity, and the defects were aggravated by the reduced cytokinin accumulation. Our results showed that local cytokinin signaling in secondary phloem regulates cambial activity noncell‐autonomously, and coordinately with its local signaling in cambium.

Fu, Xiaokang↗
DOE OSTI2023

Redox regulation in chloroplast thylakoid lumen: The pmf changes everything, again

Abstract Photosynthesis is the foundation of life on Earth. However, if not well regulated, it can also generate excessive reactive oxygen species (ROS), which can cause photodamage. Regulation of photosynthesis is highly dynamic, responding to both environmental and metabolic cues, and occurs at many levels, from light capture to energy storage and metabolic processes. One general mechanism of regulation involves the reversible oxidation and reduction of protein thiol groups, which can affect the activity of enzymes and the stability of proteins. Such redox regulation has been well studied in stromal enzymes, but more recently, evidence has emerged of redox control of thylakoid lumenal enzymes. This review/hypothesis paper summarizes the latest research and discusses several open questions and challenges to achieving effective redox control in the lumen, focusing on the distinct environments and regulatory components of the thylakoid lumen, including the need to transport electrons across the thylakoid membrane, the effects of pH changes by the proton motive force (pmf) in the stromal and lumenal compartments, and the observed differences in redox states. These constraints suggest that activated oxygen species are likely to be major regulatory contributors to lumenal thiol redox regulation, with key components and processes yet to be discovered.

Plant Sciences↗
DOE OSTI2022

Bioenergy sorghum stem growth regulation: intercalary meristem localization, development, and gene regulatory network analysis

SUMMARY Bioenergy sorghum is a highly productive drought tolerant C 4 grass that accumulates 80% of its harvestable biomass in approximately 4 m length stems. Stem internode growth is regulated by development, shading, and hormones that modulate cell proliferation in intercalary meristems (IMs). In this study, sorghum stem IMs were localized above the pulvinus at the base of elongating internodes using magnetic resonance imaging, microscopy, and transcriptome analysis. A change in cell morphology/organization occurred at the junction between the pulvinus and internode where LATERAL ORGAN BOUNDARIES ( SbLOB ), a boundary layer gene, was expressed. Inactivation of an AGCVIII kinase in DDYM ( dw2 ) resulted in decreased SbLOB expression, disrupted IM localization, and reduced internode cell proliferation. Transcriptome analysis identified approximately 1000 genes involved in cell proliferation, hormone signaling, and other functions selectively upregulated in the IM compared with a non‐meristematic stem tissue. This cohort of genes is expressed in apical dome stem tissues before localization of the IM at the base of elongating internodes. Gene regulatory network analysis identified connections between genes involved in hormone signaling and cell proliferation. The results indicate that gibberellic acid induces accumulation of growth regulatory factors (GRFs) known to interact with ANGUSTIFOLIA (SbAN3), a master regulator of cell proliferation. GRF:AN3 was predicted to induce SbARF3/ETT expression and regulate SbAN3 expression in an auxin‐dependent manner. GRFs and ARFs regulate genes involved in cytokinin and brassinosteroid signaling and cell proliferation. The results provide a molecular framework for understanding how hormone signaling regulates the expression of genes involved in cell proliferation in the stem IM.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

SU-A-210-00: AAPM Medical Physics Student Meeting: Medical Billing and Regulations: Everything You Always Wanted To Know, But Were Too Afraid To Ask

The purpose of this student annual meeting is to address topics that are becoming more relevant to medical physicists, but are not frequently addressed, especially for students and trainees just entering the field. The talk is divided into two parts: medical billing and regulations. Hsinshun Wu – Why should we learn radiation oncology billing? Many medical physicists do not like to be involved with medical billing or coding during their career. They believe billing is not their responsibility and sometimes they even refuse to participate in the billing process if given the chance. This presentation will talk about a physicist’s long career and share his own experience that knowing medical billing is not only important and necessary for every young medical physicist, but that good billing knowledge could provide a valuable contribution to his/her medical physics development. Learning Objectives: The audience will learn the basic definition of Current Procedural Terminology (CPT) codes performed in a Radiation Oncology Department. Understand the differences between hospital coding and physician-based or freestanding coding. Apply proper CPT coding for each Radiation Oncology procedure. Each procedure with its specific CPT code will be discussed in detail. The talk will focus on the process of care and use of actual workflow to understand each CPT code. Example coding of a typical Radiation Oncology procedure. Special procedure coding such as brachytherapy, proton therapy, radiosurgery, and SBRT. Maryann Abogunde – Medical physics opportunities at the Nuclear Regulatory Commission (NRC) The NRC’s responsibilities include the regulation of medical uses of byproduct (radioactive) materials and oversight of medical use end-users (licensees) through a combination of regulatory requirements, licensing, safety oversight including inspection and enforcement, operational experience evaluation, and regulatory support activities. This presentation will explore the career options for medical physicists in the NRC, how the NRC interacts with clinical medical physicists, and a physicist’s experience as a regulator. Learning Objectives: Explore non-clinical career pathways for medical physics students and trainees at the Nuclear Regulatory Commission. Overview of NRC medical applications and medical use regulations. Understand the skills needed for physicists as regulators. Abogunde is funded to attend the meeting by her employer, the NRC.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2023

Transcriptional Control of hgcAB by an ArsR-Like Regulator in Pseudodesulfovibrio mercurii ND132

The hgcAB gene pair encodes mercury (Hg) methylation capability in a diverse group of microorganisms, but its evolution and transcriptional regulation remain unknown. Working from the possibility that the evolutionary function of HgcAB may not be Hg methylation, we test a possible link to arsenic resistance. Using model Hg methylator Pseudodesulfovibrio mercurii ND132, we evaluated transcriptional control of hgcAB by a putative ArsR encoded upstream and cotranscribed with hgcAB. This regulator shares homology with ArsR repressors of arsenic resistance and S-adenosylhomocysteine (SAH)- responsive regulators of methionine biosynthesis but is distinct from other ArsR/SahR proteins in P. mercurii. Using quantitative PCR (qPCR) and RNA sequencing (RNA-seq) transcriptome analyses, we confirmed this ArsR regulates hgcAB transcription and is responsive to arsenic and SAH. Additionally, RNA-seq indicated a possible link between hgcAB activity and arsenic transformations, with significant upregulation of other ArsRregulated arsenic resistance operons alongside hgcAB. Interestingly, wild-type ND132 was less sensitive to As(V) (but not As(III)) than an hgcAB knockout strain, supporting the idea that hgcAB may be linked to arsenic resistance. Arsenic significantly impacted rates of Hg methylation by ND132; however, responses varied with culture conditions. Differences in growth and metabolic activity did not account for arsenic impacts on methylation. While arsenic significantly increased hgcAB expression, hgcAB gene and transcript abundance was not a good predictor of Hg methylation rates. Taken together, these results support the idea that Hg and As cycling are linked in P. mercurii ND132. Our results may hold clues to the evolution of hgcAB and the controls on Hg methylation in nature. This work reveals a link between microbial mercury methylation and arsenic resistance and may hold clues to the evolution of mercury methylation genes (hgcAB). Microbes with hgcAB produce methylmercury, a strong neurotoxin that readily accumulates in the food web. This study addresses a critical gap in our understanding about the environmental factors that control hgcAB expression. We show that hgcAB expression is controlled by an ArsR-like regulator responsive to both arsenic and S-adenosylhomocysteine in our model organism, Pseudodesulfovibrio mercurii ND132. Exposure to arsenic also significantly impacted Pseudodesulfovibrio mercurii ND132 mercury methylation rates. However, expression of hgcAB was not always a good predictor of Hg methylation rates, highlighting the roles of Hg bioavailability and other biochemical mechanisms in methylmercury production. This study improves our understanding of the controls on hgcAB expression, which is needed to better predict environmental methylmercury production

RNA-seq↗
DOE OSTI2017

Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica

ABSTRACT The yeast Yarrowia lipolytica is a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis in Y. lipolytica and identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase ( DGA1 ) with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination of DGA1 overexpression with nitrogen limitation resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor. IMPORTANCE The ubiquitous metabolism of lipids involves refined regulation, and an enriched understanding of this regulation would have wide implications. Various factors can influence lipid metabolism, including the environment and genetics. We demonstrated, using a multi-omics and multifactorial experimental setup, that multiple factors affect lipid accumulation in the yeast Yarrowia lipolytica . Using integrative analysis, we identified novel interactions between nutrient restriction and genetic factors involving regulators that are highly conserved among eukaryotes. Given that lipid metabolism is involved in many diseases but is also vital to the development of microbial cell factories that can provide us with sustainable fuels and oleochemicals, we envision that our report introduces foundational work to further unravel the regulation of lipid accumulation in eukaryal cells.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Isolating causal pathways between flow and fish in the regulated river hierarchy

Unregulated river systems are organized in a hierarchy in which large-scale factors (i.e., landscape and segment scales) influence local habitats (i.e., reach, meso-, and microhabitat scales), and both differentially exert selective pressures on biota. Dams, however, create discontinua in these processes and change the hierarchical structure. We examined the relative roles of hydrology and other instream factors, within a hierarchical landscape context, in organizing fish communities in regulated and unregulated tributaries to the Upper Tennessee River, USA. We also used multivariate regression trees to identify factors that partition fish assemblages based on trait similarities, irrespective of spatial scale. Then, we used classical path analysis and structural equation modeling to evaluate the most plausible hierarchical causal structure of specific trait-based community components, given the data. Both statistical approaches suggested that river regulation affects stream fishes through a variety of reach-scale variables, not always through hydrology itself. Though we observed different changes in flow, temperature, and biotic responses according to regulation types, the most predominant path in which dam regulation affected biota was via temperature alterations. Diversion dams had the strongest effects on fish assemblages. Diversion dams reduced flow magnitudes, leading to declines in fish richness but increased temperatures, leading to lower abundances in equilibrium species and nest guarders. Peaking and run-of-river dams increased flow variability, leading to lower abundances in nest-guarding fishes. Flow displayed direct relationships with biotic responses; however, results indicated that changes in temperature and substrate had equal, if not stronger, effects on fish assemblage composition. The strength and nature of relationships depended on whether flow metrics were standardized for river size. Here, we suggest that restoration efforts in regulated rivers focus on improving flow conditions in conjunction with temperature and substrate restoration.

58 GEOSCIENCES↗