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At least 919 records · Page 51
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Role of NLR family pyrin domain-containing 3 inflammasome in the activation of pancreatic stellate cells

Highlights: • NLRP3 inflammasome was activated with the extension of activation time of PSCs. • LPS triggered PSCs activation through activating NLRP3 Inflammasome. • Inhibition of NLRP3 inflammasome mitigates the activation of PSCs. • NLRP3 inflammasome activates the TGF-β1/Smad3 signaling pathway in PSCs. NLRP3 inflammasome activation plays an important role in the development of pancreatic fibrosis. However, it is unclear whether the activation of the NLRP3 inflammasome is directly involved in the activation of Pancreatic stellate cells (PSCs). The aim of this study was to investigate the role and mechanism of the NLRP3 inflammasome in the activation of PSCs. In vivo, a rat model of chronic pancreatitis (CP) was induced by intravenous injection of dibutyltin dichloride (DBTC). In vitro, rat primary PSCs were isolated from pancreatic tissues and incubated with the NLRP3 inflammasome activator LPS, the NLRP3 inhibitor MCC950, or NLRP3 siRNA. The results showed that the expression of NLRP3, pro-Caspase-1, Caspase-1 and IL-18 was increased in the rat model of CP and during PSCs activation. LPS increased the protein levels of NLRP3, ASC, Caspase-1, IL-1β and IL-18 accompanied by the upregulation of α-SMA, Col I and FN expression. Moreover, MCC950 or NLPR3 siRNA decreased the expression of α-SMA, Col I, FN, TGF-β1 and p-Smad3. Furthermore, MCC950 reversed the LPS-induced upregulation of α-SMA, FN and Col Ⅰ expression in PSCs. This study revealed that the NLRP3 inflammasome is directly involved in the activation of PSCs in vivo and in vitro. Inhibiting NLRP3 suppresses the activation of PSCs through the TGF-β1/Smad3 pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Study of Oak Ridge soils using BONCAT-FACS-Seq reveals that a large fraction of the soil microbiome is active

The ability to link soil microbial diversity to soil processes requires technologies that differentiate active subpopulations of microbes from so-called relic DNA and dormant cells. Measures of microbial activity based on various techniques including DNA labelling have suggested that most cells in soils are inactive, a fact that has been difficult to reconcile with observed high levels of bulk soil activities. We hypothesized that measures of in situ DNA synthesis may be missing the soil microbes that are metabolically active but not replicating, and we therefore applied BONCAT (Bioorthogonal Non Canonical Amino Acid Tagging) i.e. a proxy for activity that does not rely on cell division, to measure translationally active cells in soils. We compared the active population of two soil depths from Oak Ridge (TN) incubated under the same conditions for up to seven days. Depending on the soil, a maximum of 25 – 70% of the cells were active, accounting for 3-4 million cells per gram of soil type, which is an order of magnitude higher than previous estimates. The BONCAT positive cell fraction was recovered by fluorescence activated cell sorting (FACS) and identified by 16S rDNA amplicon sequencing. The diversity of the active fraction was a selected subset of the bulk soil community. Excitingly, some of the same members of the community were recruited at both depths independently from their abundance rank. On average, 86% of sequence reads recovered from the active community shared >97% sequence similarity with cultured isolates from the field site. Our observations are in line with a recent report that, of the few taxa that are both abundant and ubiquitous in soil, 45% are also cultured – and indeed some of these ubiquitous microorganisms were found to be translationally active. The use of BONCAT on soil microbiomes provides evidence that a large portion of the soil microbes can be active simultaneously. We conclude that BONCAT coupled to FACS and sequencing is effective for interrogating the active fraction of soil microbiomes in situ and provides new perspectives to link metabolic capacity to overall soil ecological traits and processes.

58 GEOSCIENCES↗
DOE OSTI2022

Future directions for active matter on ordered substrates

Active matter is a term encompassing particle-based assemblies with some form of self-propulsion, including certain biological systems as well as synthetic systems such as artificial colloidal swimmers, all of which can exhibit a remarkable variety of new kinds of nonequilibrium phenomena. A wealth of non-active condensed matter systems can be described in terms of a collection of particles coupled to periodic substrates, leading to the emergence of commensurate-incommensurate effects, Mott phases, tribology effects, and pattern formation. It is natural to ask how such phases are modified when the system is active. Here we provide an overview and future directions for studying individual and collectively interacting active matter particles coupled to periodic substrates, where new types of commensuration effects, directional locking, and active phases can occur. Importantly, further directions for exploration include directional locking effects, the realization of active solitons or active defects in incommensurate phases, active Mott phases, active artificial spin ice, active doping transitions, active floating phases, active surface physics, active matter time crystals, and active tribology.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

Alkali-activated Class F Fly Ash-rich Portland Cement Blends as Alternative Thermal Shock Resistant Cements

This study focused on evaluating the resistance of 300°C-autocalved alkali-activing Class F fly ash (FAF)-rich Type II Ordinary Portland Cement (OPC) blends with 80/20 and 90/10 FAF/OPC ratios to five thermal-shock (TS) fatigue cycles (one cycle, 600°C heat – 25°C water quenching). The factors to be evaluated included the hydration behaviors, crystalline/ amorphous phaseidentifications, -compositions and -transformations, and microstructural-developments andalterations for blended cements assembled by three different alkaline activators, sodium metasilicate (SMS), soda ash (SA), and sodium sulfate (SS). All factors were related directory to the changes in compressive strength after TS testing. The setting time of cement slurries at 25° and 85°C depended on the alkaline activators; SMS and SA contributing to a strong alkalinity hastened setting, while SS with moderate alkalinity extended the setting time. A more prolonged setting time was observed from non-activated cement. In this case, there were two separated hydration reactions: The first reaction was the hydration of OPC; the second one was associated with the dissolution and pozzolanic activity of FAF. In contrast, all alkali- activated cements engendered the concomitant hydration of OPC and FAF, thereby conferring a higher compressive strength on them than that of the non-activator one. The principal contributor to the development of strength of both the non-activated and activated cements at 300°C was the amorphous NaO 2 - or CaO-Al 2 O 3 - SiO 2 -H 2 O (N,C-A-S-H) phase formed by the interactions between alkaline activator, OPC, and FAF. This phase played an important role in minimizing the loss in strength after TS. On the other hand, adding SMS and SA introduced the mixed crystalline FAF-OPC hydrates, such as garranite and wairakite, as the major phases, into the autoclaved cement bodies. Also, these activators induced the formation of two FAF-related crystalline hydrates, analcime as the major phase and riversidelite (0.9 nm tobermorite) as the minor one. However, these identified phases were sensitive to TS, so converting the major phases into minor phases or vanishment. In contrast, three crystalline phases including calcite and anhydrous sodium sulfate as the major ones and 1.1 nm tobermorite as the minor one, that formed in non-activated and activated cements remained unchanged after TS. Additionally, SAactivated cement revealed porous microstructure created by the incorporation of copious amount of carbonate reaction products into the cement, raising concerns that cements might enhance the rate of water transportation and reduce compressive strength. Nevertheless, TS-insensitive amorphous N,C-A-S-H phase as the major cementitions structure coexisting with TS-insensitive crystalline products were responsible for sustaining the integrity of alkali-activated FAF-rich OPC cement systems in such harsh heat-cooling fatigue environments.

15 GEOTHERMAL ENERGY↗
NASA NTRS2009

The Maximum Free Magnetic Energy Allowed in a Solar Active Region

Two whole-active-region magnetic quantities that can be measured from a line-of-sight magnetogram are (sup L) WL(sub SG), a gauge of the total free energy in an active region's magnetic field, and sup L(sub theta), a measure of the active region's total magnetic flux. From these two quantities measured from 1865 SOHO/MDI magnetograms that tracked 44 sunspot active regions across the 0.5 R(sub Sun) central disk, together with each active region's observed production of CMEs, X flares, and M flares, Falconer et al (2009, ApJ, submitted) found that (1) active regions have a maximum attainable free magnetic energy that increases with the magnetic size (sup L) (sub theta) of the active region, (2) in (Log (sup L)WL(sub SG), Log(sup L) theta) space, CME/flare-productive active regions are concentrated in a straight-line main sequence along which the free magnetic energy is near its upper limit, and (3) X and M flares are restricted to large active regions. Here, from (a) these results, (b) the observation that even the greatest X flares produce at most only subtle changes in active region magnetograms, and (c) measurements from MSFC vector magnetograms and from MDI line-of-sight magnetograms showing that practically all sunspot active regions have nearly the same area-averaged magnetic field strength: =- theta/A approximately equal to 300 G, where theta is the active region's total photospheric flux of field stronger than 100 G and A is the area of that flux, we infer that (1) the maximum allowed ratio of an active region's free magnetic energy to its potential-field energy is ~1, and (2) any one CME/flare eruption releases no more than a small fraction (less than ~10%) of the active region's free magnetic energy. This work was funded by NASA's Heliophysics Division and NSF's Division of Atmospheric Sciences.

Moore, Ronald L.↗
NASA NTRS2012

The Limit of Free Magnetic Energy in Active Regions

By measuring from active-region magnetograms a proxy of the free energy in the active region fs magnetic field, it has been found previously that (1) there is an abrupt upper limit to the free energy the field can hold that increases with the amount of magnetic field in the active region, the active region fs magnetic flux content, and (2) the free energy is usually near its limit when the field explodes in a CME/flare eruption. That is, explosive active regions are concentrated in a main-sequence path bordering the free-energy ]limit line in (flux content, free-energy proxy) phase space. Here, from measurement of Marshall Space Flight Center vector magnetograms, we find the magnetic condition that underlies the free ]energy limit and the accompanying main sequence of explosive active regions. Using a suitable free ]energy proxy measured from vector magnetograms of 44 active regions, we find that (1) in active regions at and near their free ]energy limit, the ratio of magnetic-shear free energy to the non ]free magnetic energy the potential field would have is approximately 1 in the core field, the field rooted along the neutral line, and (2) this ratio is progressively less in active regions progressively farther below their free ]energy limit. This shows that most active regions in which this core-field energy ratio is much less than 1 cannot be triggered to explode; as this ratio approaches 1, most active regions become capable of exploding; and when this ratio is 1 or greater, most active regions are compelled to explode. From these results we surmise the magnetic condition that determines the free ]energy limit is the ratio of the free magnetic energy to the non-free energy the active region fs field would have were it completely relaxed to its potential ]field configuration, and that this ratio is approximately 1 at the free-energy limit and in the main sequence of explosive active regions.

Moore, Ron↗
DOE OSTI2016

Determination of Activity of Neodymium(III) in Molten Eutectic LiCl-KCl using Electrochemical Methods

The pyrochemical recycling of actinides is a promising option for closing the nuclear fuel cycle. The technology is particularly attractive for recycle of metallic and molten salt fuels. The Republic of Korea is also taking a serious look at the application of pyrochemical treatment of used oxide fuel from Pressurized Water Reactors (PWR). The science behind pyrochemical recycling is being actively studied at the various national labs and universities. The Rare Earth Drawdown process is proposed to be included in a commercial pyrochemical recycling facility in order to minimize the amount of waste generated from the processing that will require permanent disposal in a geological repository. This process involves selective extraction of rare earth elements from electro-refiner salt. The salt can then be further processed to selectively remove Group I-II active metals and eventually be recycled back to the electro-refiner. The preferred method of separation of the rare earths from the salt is using electrolysis due to its inherent selectivity and ease of operation. The purpose of this study is to evaluate the effects of the presence of cesium (Group I) on the electrochemical behavior of neodymium in a molten eutectic LiCl-KCl salt. The activity and by extension the activity coefficient of a species determines many of the key electrochemical properties such as apparent reduction potential. In this study, we have undertaken a series of experiments to experimentally determine the activity coefficient of the dissolved neodymium(III) ions as a function of concentration, both in the presence and absence of cesium. This was done using a first of its kind electrochemical cell. Previously, activity of dissolved species has been determined using electrochemical cells in which equilibrium potentials are measured for the Nd/Nd(III) versus a Ag/AgCl reference electrode. There are several issues associated with such an approach. These electrodes are associated with several sources of errors; indeterminate values of Standard Reduction Potentials of (E{sup θ}) for Ag and Nd in molten salts, unknown liquid junction potentials and potential drifts. These uncertainties contribute errors to the experimental measurements. For this study, we employed a Nd/LiCl-KCl-NdCl{sub 3(Saturatedelectrode)}. There are several advantages with using such an electrode. If the expanded Nernst Equation is written for the aforementioned electrochemical cell, all of the terms cancel out except the activity term. This enables us to directly experimentally measure the activity of the species in solution. When we use a saturated NdCl{sub 3} reference electrode, the activity that is measured is defined as the activity versus a 'Saturated Solid State'. To determine the activity coefficients, we need to determine the activity versus the 'Liquid Standard Sate'. To convert the activity from solid standard state to liquid standard state, we correct for it using the hypothetical Gibbs free energy of fusion for neodymium chloride. (authors)

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2016

4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells

The aim of the present study is to investigate the potential anti-hepatocellular carcinoma (HCC) cell activity by 4SC-202, a novel class I HDAC inhibitor (HDACi). The associated signaling mechanisms were also analyzed. We showed that 4SC-202 treatment induced potent cytotoxic and proliferation–inhibitory activities against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, adding 4SC-202 in HCC cells activated mitochondrial apoptosis pathway, which was evidenced by mitochondrial permeability transition pore (mPTP) opening, cytochrome C cytosol release and caspase-3/-9 activation. Inhibition of this apoptosis pathway, by caspase-3/-9 inhibitors, mPTP blockers, or by shRNA-mediated knockdown of cyclophilin-D (Cyp-D, a key component of mPTP), significantly attenuated 4SC-202-induced HCC cell death and apoptosis. Reversely, over-expression of Cyp-D enhanced 4SC-202's sensitivity in HCC cells. Further studies showed that 4SC-202 induced apoptosis signal-regulating kinase 1 (ASK1) activation, causing it translocation to mitochondria and physical association with Cyp-D. This mitochondrial ASK1-Cyp-D complexation appeared required for mediating 4SC-202-induced apoptosis activation. ASK1 stable knockdown by targeted-shRNAs largely inhibited 4SC-202-induced mPTP opening, cytochrome C release, and following HCC cell apoptotic death. Together, we suggest that 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to potently inhibit human HCC cells. - Highlights: • 4SC-202 exerts potent anti-proliferative and cytotoxic activity against established/primary HCC cells. • SC-202-induced anti-HCC cell activity relies on caspase-dependent apoptosis activation. • 4SC-202 activates Cyp-D-dependent mitochondrial apoptosis pathway in HCC cells. • 4SC-202 activates ASK1 in HCC cells, causing it translocation to mitochondria. • Mitochondrial ASK1-Cyp-D complexation mediates 4SC-202's activity in HCC cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Interleukin-enhanced binding factor 2 interacts with NLRP3 to inhibit the NLRP3 inflammasome activation

Highlights: • The NLRP3 inflammasome activation is attenuated by PSMD10, BCL2L10, CTSS, and ILF2. • ILF2 represses inflammasome activation, pro-Casp-1 cleavege, and pro-IL-1β maturation. • ILF2 interacts with NLRP3 to inhibit the inflammasome activation in the cytoplasm. • ILF2 represses ATP-induced activation of endogenous NLRP3 inflammasome in macrophages. The activation of the NLRP3 inflammasome is a key process of host immune response that establishes the first line of defense against pathogen infections and cellular stresses, whereas excessive inflammasome activation may damage the hosts, and thus it must be precisely controlled. However, the mechanism underlying the repression of the NLRP3 inflammasome activation remains largely unknown. In this study, by establishing and using a reconstructed NLRP3 inflammasome activation system, we reveal that the NLRP3 inflammasome activation, pro-caspase-1 cleavage, and pro-interleukin-1β (pro-IL-1β) activation are repressed by the interleukin-enhanced binding factor 2 (ILF2). Further studies demonstrate that ILF2 represses the activation of NLRP3 inflammasome through interacting with the NACHT-associated domain (NAD) of NLRP3 and co-localized with NLRP3 in the cytoplasm of HEK293T cells. Finally, by generating a THP-1 cell line stably expressing ILF2 protein using the lentivirus infection system, we demonstrate that ILF2 represses ATP-induced activation of endogenous NLRP3 inflammasome in macrophages. Therefore, this study identifies a new role of ILF2 in the regulation of the NLRP3 inflammasome, and reveals a unique mechanism underlying the repression of the NLRP3 inflammasome activation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MALT1 activation by TRAF6 needs neither BCL10 nor CARD11

Highlights: • TRAF6 is not strictly required for MALT1 activation downstream of CARD11/BCL10. • TRAF6 can activate MALT1 independently of CARD11 or BCL10. • MALT1 oligomerization is involved in its activation by TRAF6. • Pathways leading to TRAF6 oligomerization may broaden the range of MALT1 activation mechanisms. The MALT1 (Mucosa associated lymphoid tissue lymphoma translocation protein 1) paracaspase couples antigen receptors on lymphocytes to downstream signaling events. Activation of MALT1 is known to involve stimulus-dependent CBM complex formation, that is, the recruitment of BCL10-bound MALT1 to a CARD-Coiled Coil protein. Beyond this canonical, CBM-dependent mechanism of MALT1 activation, recent studies suggest that MALT1 protease activity may be triggered by alternative mechanisms. For instance, the E3-ligase TRAF6 can activate MALT1 proteolytic function and induce MALT1 auto-cleavage. However, the interplay between CBM and TRAF6 with regard to MALT1 activation has remained incompletely elucidated. Here, by generating CRISPR/Cas9-derived knock-out Jurkat T-cells, we show that TRAF6 was dispensable for CARD11/BCL10-dependent MALT1 activation upon T-cell stimulation. However, ectopically-expressed TRAF6 could induce MALT1 activity in Jurkat T-cells devoid of either CARD11 or BCL10. These data provide unequivocal evidence that TRAF6-mediated MALT1 activation does not require the upstream scaffold CARD11 or the interaction between MALT1 and BCL10. Thus, TRAF6 may be part of a previously unidentified non-canonical pathway that triggers MALT1 protease activity independently of canonical CBM signalosomes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Profilin facilitates PKCε activation by accelerating ATP supply

Higghlights• Profilin associates with activated PKCε. • Profilin does not activate PKCε directly. • Profilin facilitates PKCε activation by accelerating ATP supply. Profilin catalyzes the exchange of actin-bound ADP to ATP. The present study investigated the role of profilin in PKCε activation. Profilin associated with PKCε in differentiated PC-12 cells under the basal conditions, which was inhibited by the PKC inhibitor GF109203X. The selective PKCε activator DCP-LA markedly increased the association, which was clearly prevented by GF109203X. The basal PKC activity in PC-12 cells was attenuated by knocking-down profilin, while the basal activities of PKA and CaMKII were not affected. DCP-LA enhanced the PKC activity to approximately 3.5 folds of the basal levels, and the effect was suppressed by knocking-down profilin. In the cell-free system, PKCε was not activated by profilin alone. DCP-LA activated PKCε in an ATP concentration (2–500 μM)-dependent manner, and addition of profilin shifted the ATP concentration/DCP-LA-induced PKCε activity relation curve to the left (the direction of lower ATP concentrations). Taken together, the results of the present study indicate that profilin binds to activated PKCε and facilitates PKCε activation by accelerating ATP supply to PKCε.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Association of lead, cadmium and mercury with paraoxonase 1 activity and malondialdehyde in a general population in Southern Brazil

Metal exposure is associated with increased oxidative stress (OS), which is considered an underlying mechanism of metal-induced toxicity. Malondialdehyde (MDA) is a final product of lipid peroxidation, and it has been extensively used to evaluate metal-induced OS. Pro-oxidant effects produced by metals can be mitigated by paraoxonase 1 (PON1), an antioxidant enzyme known to prevent cardiovascular disease and atherosclerosis. Among other factors, the Q192R polymorphism and the exposure to heavy metals have been known to alter PON1 activity. Here, we evaluated the association of blood lead (Pb), cadmium (Cd) and mercury (Hg) levels with PON1 activity, and with MDA concentrations in a randomly selected sample of Brazilian adults aged 40 years or older, living in an urban area in Southern Brazil. A total of 889 subjects were evaluated for blood Pb and Cd levels, and 832 were tested for Hg. Geometric mean of blood Pb, Cd and Hg was 1.93 μg/dL, 0.06 μg/L and 1.40 μg/L, respectively. PON1 activity was significantly different among various genotypes: QQ (PON1=121.4 U/mL), QR (PON1=87.5 U/mL), and RR (PON1=55.2 U/mL), p<0.001. PON1 genotypes were associated only with Cd blood levels. Those with QR genotype had Cd concentrations higher (0.07 μg/L) than those with the RR genotype (0.04 μg/L) with p=0.034. However, PON1 activity was not significantly associated with metal concentrations. Cluster analysis showed that men who reported to be current smokers and drinkers with higher blood Pb and Cd levels, had significantly lower PON1 activity than non-smokers or -drinkers, and women with lower Pb and Cd levels. RR genotype carriers had lower PON1 activity than those with the QR genotype, and had higher levels of Pb and Cd compared with other genotype carriers. For blood Hg, no association with PON1 activity or genotype was noted. We found low levels of Pb, Cd and Hg in environmentally exposed Brazilian adults. Cd concentrations were increased in subjects with QR genotype. Those with RR genotype had lower PON1 activity and higher levels of Pb and Cd than other genotype carriers. The results of cluster analysis suggested that smoking status exerts a significant influence on PON1 activity. Other studies with environmentally exposed populations are required to further clarify whether low blood levels of metals influence OS biomarkers. - Highlights: • Low levels of lead, cadmium and mercury were found in a sample of Brazilian adults. • PON1 activity and MDA was not significantly associated with metals concentrations. • Blood cadmium was significantly different according with PON1 genotypes, and RR genotype carriers had lower PON1 activity and higher Pb and Cd levels. • Men, smokers, drinkers, with higher blood Pb and Cd levels had lower PON1 activity. • There was not a trend of an association with PON1 activity or genotype with blood mercury.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Metabolism of UV-filter benzophenone-3 by rat and human liver microsomes and its effect on endocrine-disrupting activity

Benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3) is widely used as sunscreen for protection of human skin and hair from damage by ultraviolet (UV) radiation. In this study, we examined the metabolism of BP-3 by rat and human liver microsomes, and the estrogenic and anti-androgenic activities of the metabolites. When BP-3 was incubated with rat liver microsomes in the presence of NADPH, 2,4,5-trihydroxybenzophenone (2,4,5-triOH BP) and 3-hydroxylated BP-3 (3-OH BP-3) were newly identified as metabolites, together with previously detected metabolites 5-hydroxylated BP-3 (5-OH BP-3), a 4-desmethylated metabolite (2,4-diOH BP) and 2,3,4-trihydroxybenzophenone (2,3,4-triOH BP). In studies with recombinant rat cytochrome P450, 3-OH BP-3 and 2,4,5-triOH BP were mainly formed by CYP1A1. BP-3 was also metabolized by human liver microsomes and CYP isoforms. In estrogen reporter (ER) assays using estrogen-responsive CHO cells, 2,4-diOH BP exhibited stronger estrogenic activity, 2,3,4-triOH BP exhibited similar activity, and 5-OH BP-3, 2,4,5-triOH BP and 3-OH BP-3 showed lower activity as compared to BP-3. Structural requirements for activity were investigated in a series of 14 BP-3 derivatives. When BP-3 was incubated with liver microsomes from untreated rats or phenobarbital-, 3-methylcholanthrene-, or acetone-treated rats in the presence of NADPH, estrogenic activity was increased. However, liver microsomes from dexamethasone-treated rats showed decreased estrogenic activity due to formation of inactive 5-OH BP-3 and reduced formation of active 2,4-diOH BP. Anti-androgenic activity of BP-3 was decreased after incubation with liver microsomes. - Highlights: • Metabolic modification of the endocrine-disrupting activity of BP-3 was examined. • 2,4,5-TriOH BP and 3-OH BP-3 were identified as new BP-3 metabolites. • 2,4-DiOH BP and 2,3,4-triOH BP exhibited high or similar estrogenic activities. • Estrogenic activity of BP-3 was enhanced by incubation with rat liver microsomes. • Structural requirements for the activities of BP-3 derivatives were demonstrated.

3-METHYLCHOLANTHRENE↗
DOE OSTI2018

Effects of the tumor suppressor PTEN on biological behaviors of activated pancreatic stellate cells in pancreatic fibrosis

Highlights: • The PTEN level decreased in DBTC-induced pancreatic fibrosis. • PTEN expression correlates with the activation and apoptosis of PSCs in vivo. • PTEN modulation of activated PSCs involves the AKT and FAK/ERK pathways. • WT PTEN affects anti-fibrotic activity by regulating PSC behaviors in vitro. Pancreatic stellate cells (PSCs), when activated, are characterized by proliferation and collagen synthesis, and contribute to extracellular matrix deposition in pancreatic fibrosis. Concomitantly, fibrosis is linked with the loss of PTEN (phosphatase and tensin homolog) protein in several organs. This study investigated the association between PTEN protein levels and the activated or apoptotic status of PSCs in a rat model of chronic pancreatitis. In addition, the activation status and biological behaviors of culture-activated PSCs were analyzed after lentiviral transfection with wildtype or mutant (G129E) PTEN for upregulation, or PTEN short hairpin RNA for downregulation, of PTEN. In vivo, PTEN levels gradually decreased during pancreatic fibrosis, which positively correlated with apoptosis of activated PSCs, but negatively with PSC activation. In vitro, activated PSCs with wildtype PTEN showed less proliferation, migration, and collagen synthesis compared with control PSCs, and greater numbers were apoptotic; activated PSCs with mutant PTEN showed similar, but weaker, effects. Furthermore, AKT and FAK/ERK signaling was involved in this process. In summary, activated PSCs during pancreatic fibrosis in vivo have lower levels of PTEN. In vitro, PTEN appears to prevent PSCs from further activation and promotes apoptosis through regulation of the AKT and FAK/ERK pathways.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

A Probe-Enabled Approach for the Selective Isolation and Characterization of Functionally Active Subpopulations in the Gut Microbiome

Increasing evidence has shown that microorganisms present in the mammalian gut have a major impact on the metabolism of xenobiotics – chemicals foreign to the body including drugs and environmental contaminants – either by modulating host metabolism or by transforming xenobiotics or their metabolites directly. Being able to predict these interactions will be critical to develop precision medicine strategies utilizing the gut microbiota. However, current knowledge of which microbes are responsible for a given activity is severely limited and is further complicated by the sheer diversity of gut microbes between individuals. Current approaches including metagenomic and metatranscriptomic analyses can only identify enzymes and organisms that have the potential to catalyze a specific reaction, but cannot determine if an enzyme is truly active within the gut. To identify the microorganisms that are directly responsible for an activity in the gut of an individual, new functional approaches are needed. Here, we present an activity-based probe (ABP) approach to define the microbial populations responsible for a specific xenobiotic metabolizing activity. We developed an ABP for β-glucuronidases, enzymes capable of reversing a major pathway in phase II metabolism that is responsible for xenobiotic elimination. Using this ABP, we covalently labelled active β-glucuronidases both in vitro and in bacterial cells in the mouse gut microbiota. Cells possessing β-glucuronidase activity were then fluorescently labeled, isolated using fluorescence-activated cell sorting (FACS), and identified by sequencing. We found that glucuronidase active bacteria in the murine gut are taxonomically diverse, and even within phyla the taxa displaying function are highly disparate. Perturbation of the gut microbiota with vancomycin decreased but did not eliminate β-glucuronidase activity, which corresponded to a shift in the β-glucuronidase active population. These data demonstrate that the metabolic activity of the gut microbiota can be plastic and that during perturbation, functional capacity may be maintained by phylogenetically disparate populations. This work highlights the utility of ABPs to identify currently unknown functional microbial subpopulations responsible for a specific activity of interest within the gut of an individual.

Whidbey, Christopher↗
DOE OSTI2025

Arsenic activation and compensation in single crystal CdTe bilayers

In state-of-the art polycrystalline CdTe photovoltaics, group-V dopant activation is about 2%. Low activation can create electronic defects and lead to recombination and band tail losses. To develop methods to overcome this limitation, dopant activation was systematically investigated using molecular beam epitaxy (MBE) grown single crystal bilayers of As-doped CdTe on undoped CdTe. Results suggest multiple paths for improved As-activation in polycrystalline CdTe-based devices. It was found that the carrier concentration in this MBE material saturated at ∼3 × 1016 cm−3, with high levels (>50%) of As-activation possible. High activation could be achieved with a post-growth activation temperature of ∼450 °C, when the initial doping level was below the saturation level. However, at typical polycrystalline As incorporation levels (>5 × 1016 cm−3), the excess As is inactive or compensating, requiring elevated temperatures (500–600 °C) to achieve high activation. Oxygen in the annealing ambient was detrimental, while the effect of CdCl2 in the ambient is more case-dependent. A 575 °C activation anneal was combined with a 450 °C CdCl2 treatment to better understand the implications for polycrystalline CdTe. Interestingly, on highly doped samples, processes ending with a high temperature step displayed high activation, while those ending at 450 °C significantly reduced the carrier concentration (with or without CdCl2 in the ambient). Low activation can be restored with another high temperature anneal, allowing reproducible toggling between high and low activation based on the final temperature. Photoluminescence revealed the presence of donor–acceptor pairs in the low activation state that appear to be associated with a compensating defect.

14 SOLAR ENERGY↗
DOE OSTI2023

Promoting Physical Activity During Pregnancy and the Postpartum Period

Introduction Physical activity is important for improving and maintaining overall health across the life span, including during and after pregnancy. Achieving recommended levels of physical activity can be challenging during pregnancy and the postpartum period. The US Office of Disease Prevention and Health Promotion sought to promote physical activity during and after pregnancy through the development of health education materials for the Move Your Way campaign. Research was conducted with pregnant and postpartum people to learn what types of messages and materials would encourage physical activity in these populations. Methods Participants were recruited from 3 regions of the United States to participate in 90‐minute virtual focus groups. Eligible participants were aged 18 years or older and either pregnant or 6 weeks to 1 year postpartum. Participants were asked questions about their beliefs, attitudes, and perceptions about physical activity and prompted to provide feedback on health promotion messages and images. Sessions were recorded, transcribed, and analyzed for key themes. Results Twenty‐four focus groups were conducted with 48 pregnant participants and 52 postpartum participants. Sixteen sessions were conducted in English and 8 were conducted in Spanish. Most participants had questions about how much physical activity is recommended, and many cited their health care provider as a trusted source of information. Participants responded positively to materials that acknowledged the uniqueness of each pregnant or postpartum experience, referenced gradually increasing physical activity levels, highlighted the benefits of physical activity, focused on safety, addressed common barriers, and displayed realistic representations of physical activity. Discussion There is an opportunity to improve messaging about physical activity during and after pregnancy. To better promote physical activity, perinatal health care providers and other health professionals can share information about recommended amounts of physical activity, communicate the benefits, and promote realistic and achievable physical activity messages that address common barriers in these populations.

Nursing↗
DOE OSTI2024

The Active Asteroids Citizen Science Program: Overview and First Results

Abstract We present the Citizen Science program Active Asteroids and describe discoveries stemming from our ongoing project. Our NASA Partner program is hosted on the Zooniverse online platform and launched on 2021 August 31, with the goal of engaging the community in the search for active asteroids—asteroids with comet-like tails or comae. We also set out to identify other unusual active solar system objects, such as active Centaurs, active quasi-Hilda asteroids (QHAs), and Jupiter-family comets (JFCs). Active objects are rare in large part because they are difficult to identify, so we ask volunteers to assist us in searching for active bodies in our collection of millions of images of known minor planets. We produced these cutout images with our project pipeline that makes use of publicly available Dark Energy Camera data. Since the project launch, roughly 8300 volunteers have scrutinized some 430,000 images to great effect, which we describe in this work. In total, we have identified previously unknown activity on 15 asteroids, plus one Centaur, that were thought to be asteroidal (i.e., inactive). Of the asteroids, we classify four as active QHAs, seven as JFCs, and four as active asteroids, consisting of one main-belt comet (MBC) and three MBC candidates. We also include our findings concerning known active objects that our program facilitated, an unanticipated avenue of scientific discovery. These include discovering activity occurring during an orbital epoch for which objects were not known to be active, and the reclassification of objects based on our dynamical analyses.

Astronomy & Astrophysics↗