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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 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Saturation of SERCA's lipid annulus may protect against its thermal inactivation

The sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase (SERCA) pumps are integral membrane proteins that catalyze the active transport of Ca{sup 2+} into the sarcoplasmic reticulum, thereby eliciting muscle relaxation. SERCA pumps are highly susceptible to oxidative damage, and cytoprotection of SERCA dampens thermal inactivation and is a viable therapeutic strategy in combating diseases where SERCA activity is impaired, such as muscular dystrophy. Here, we sought to determine whether increasing the percent of saturated fatty acids (SFA) within SERCA's lipid annulus through diet could protect SERCA pumps from thermal inactivation. Female Wistar rats were fed either a semi-purified control diet (AIN93G, 7% soybean oil by weight) or a modified AIN93G diet containing high SFA (20% lard by weight) for 17 weeks. Soleus muscles were extracted and SERCA lipid annulus and activity under thermal stress were analyzed. Our results show that SERCA's lipid annulus is abundant with short-chain (12–14 carbon) fatty acids, which corresponds well with SERCA's predicted bilayer thickness of 21 Å. Under control-fed conditions, SERCA's lipid annulus was already highly saturated (79%), and high-fat feeding did not increase this any further. High-fat feeding did not mitigate the reductions in SERCA activity seen with thermal stress; however, correlational analyses revealed significant and strong associations between % SFA and thermal stability of SERCA activity with greater %SFA being associated with lower thermal inactivation and greater % polyunsaturation and unsaturation index being associated with increased thermal inactivation. Altogether, these findings show that SERCA's lipid annulus may influence its susceptibility to oxidative damage, which could have implications in muscular dystrophy and age-related muscle wasting. - Highlights: • SERCA's lipid annulus in rat soleus was measured after immunoconcentration. • Short fatty acid chains surround SERCA and may ensure optimal hydrophobic matching. • SERCA's annulus is highly saturated in control-fed and high-fat fed rats. • Greater saturation associates with small levels of thermal inactivation. • Greater unsaturation associates with large levels of thermal inactivation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced Cyp2b10 and Cyp3a11 (CAR/PXR target genes) • Aroclor 1260 at 200 mg/kg induced Cyp1a2 (AhR target gene)

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet. • Genistein modulation of neutrophils is associated with blood glucose levels.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153

Early life exposure to endocrine disrupting compounds has been linked to chronic diseases later in life, like obesity and related metabolic disorders. We exposed C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androstane receptor/pregnane X receptor agonist polychlorinated biphenyl 153 (PCB 153) in an experimental design relevant for human exposure. Exposure occurred during gestation and lactation via maternal feed to a wide dose range (TCDD: 10–10,000 pg/kg body weight/day; PCB 153: 0.09–1406 μg/kg body weight/d). Then exposure was ceased and offspring were followed up to 1 year of age. Metabolic parameters like body weight, fat pad weights, glucose tolerance, endocrine serum profile, and neurobehavioral and immunological parameters were determined. Body weight was transiently affected by both compounds throughout the follow-up. TCDD-exposed males showed decreased fat pad and spleen weights and an increase in IL-4 production of splenic immune cells. In contrast, females showed increased fat pad weights and production of IFNγ. PCB 153-exposed males showed an increase in glucose, whereas females showed an increase in glucagon, a decrease in pancreas weight, and an increase in thymus weight. In conclusion, early life exposure to TCDD appears to affect programming of energy and immune homeostasis in offspring, whereas the effects of perinatal PCB 153 were mainly on programming of glucose homeostasis. Both compounds act sex-specifically. Lowest derived BMDLs (lower bounds of the (two sided) 90%-confidence interval for the benchmark dose) for both compounds are not lower than current tolerable daily intakes. - Highlights: • Early life exposure to TCDD affects programming of energy and immune homeostasis. • Early life exposure to PCB 153 affects programming of energy homeostasis. • Both compounds act sex-specifically. • Lowest derived BMDLs for both TCDD and PCB 153 are not lower than current tolerable daily intakes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

MO-G-17A-03: MR-Based Cortical Bone Segmentation for PET Attenuation Correction with a Non-UTE 3D Fast GRE Sequence

Purpose: To determine the feasibility of identifying cortical bone on MR images with a short-TE 3D fast-GRE sequence for attenuation correction of PET data in PET/MR. Methods: A water-fat-bone phantom was constructed with two pieces of beef shank. MR scans were performed on a 3T MR scanner (GE Discovery™ MR750). A 3D GRE sequence was first employed to measure the level of residual signal in cortical bone (TE{sub 1}/TE{sub 2}/TE{sub 3}=2.2/4.4/6.6ms, TR=20ms, flip angle=25°). For cortical bone segmentation, a 3D fast-GRE sequence (TE/TR=0.7/1.9ms, acquisition voxel size=2.5×2.5×3mm{sup 3}) was implemented along with a 3D Dixon sequence (TE{sub 1}/TE{sub 2}/TR=1.2/2.3/4.0ms, acquisition voxel size=1.25×1.25×3mm{sup 3}) for water/fat imaging. Flip angle (10°), acquisition bandwidth (250kHz), FOV (480×480×144mm{sup 3}) and reconstructed voxel size (0.94×0.94×1.5mm{sup 3}) were kept the same for both sequences. Soft tissue and fat tissue were first segmented on the reconstructed water/fat image. A tissue mask was created by combining the segmented water/fat masks, which was then applied on the fast-GRE image (MRFGRE). A second mask was created to remove the Gibbs artifacts present in regions in close vicinity to the phantom. MRFGRE data was smoothed with a 3D anisotropic diffusion filter for noise reduction, after which cortical bone and air was separated using a threshold determined from the histogram. Results: There is signal in the cortical bone region in the 3D GRE images, indicating the possibility of separating cortical bone and air based on signal intensity from short-TE MR image. The acquisition time for the 3D fast-GRE sequence was 17s, which can be reduced to less than 10s with parallel imaging. The attenuation image created from water-fat-bone segmentation is visually similar compared to reference CT. Conclusion: Cortical bone and air can be separated based on intensity in MR image with a short-TE 3D fast-GRE sequence. Further research is required to optimize the strategy to reduce Gibbs artifacts.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-I-62: Reduction of Susceptibility Artifacts by Increasing the Bandwidth (BW) and Echo Train Length (ETL)

Purpose: The aim of this present study is to increase bandwidth (BW) and echo train length (ETL) in Proton Density Turbo Spin Echo (PD TSE) sequences with and without fat saturation (FS) as well as in Turbo Inversion Recovery Magnitude sequences (TIRM) in order to assess whether these sequences are capable of reducing susceptibility artifacts. Methods: We compared 1) TIRM coronal (COR) with the same sequence with increased both BW and ETL 2) Conventional PD TSE sagittal (SAG) with FS with an increased BW 3) Conventional PD TSE SAG without FS with an increased BW 4) Conventional PD TSE SAG without FS with increased both BW and ETL. A quantitative analysis was performed to measure the extent of the susceptibility artifacts. Furthermore, a qualitative analysis was performed by two radiologists in order to evaluate the susceptibility artifacts, image distortion and fat suppression. The depiction of cartilage, menisci, muscles, tendons and bone marrow were also qualitatively analyzed. Results: The quantitative analysis found that the modified TIRM sequence is significantly superior to the conventional one regarding the extent of the susceptibility artifacts. In the qualitative analysis, the modified TIRM sequence was superior to the corresponding conventional one in eight characteristics out of ten that were analyzed. The modified PD TSE with FS was superior to the corresponding conventional one regarding the susceptibility artifacts, image distortion and depiction of bone marrow and cartilage while achieving effective fat saturation. The modified PD TSE sequence without FS with a high (H) BW was found to be superior corresponding to the conventional one in the case of cartilage. Conclusion: Consequently, TIRM sequence with an increased BW and ETL is proposed for producing images of high quality and modified PD TSE with H BW for smaller metals, especially when FS is used.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

TU-AB-201-11: A Novel Theoretical Framework for MRI-Only Image Guided LDR Prostate and Breast Brachytherapy Implant Dosimetry

Purpose: To propose a novel framework for accurate model-based dose calculations using only MR images for LDR prostate and breast seed implant brachytherapy. Methods: Model-based dose calculation methodologies recommended by TG-186 require further knowledge about specific tissue composition, which is challenging with MRI. However, relying on MRI-only for implant dosimetry would reduce the soft tissue delineation uncertainty, costs, and uncertainties associated with multi-modality registration and fusion processes. We propose a novel framework to address this problem using quantitative MRI acquisitions and reconstruction techniques. The framework includes three steps: (1) Identify the locations of seeds(2) Identify the presence (or absence) of calcification(s)(3) Quantify the water and fat content in the underlying tissueSteps (1) and (2) consider the sources that limit patient dosimetry, particularly the inter-seed attenuation and the calcified regions; while step (3) targets the quantification of the tissue composition to consider the heterogeneities in the medium. Our preliminary work has shown that the seeds and the calcifications can be identified with MRI using both the magnitude and the phase images. By employing susceptibility-weighted imaging with specific post-processing techniques, the phase images can be further explored to distinguish the seeds from the calcifications. Absolute quantification of tissue, water, and fat content is feasible and was previously demonstrated in phantoms and in-vivo applications, particularly for brain diseases. The approach relies on the proportionality of the MR signal to the number of protons in an image volume. By employing appropriate correction algorithms for T1 - and T2*-related biases, B1 transmit and receive field inhomogeneities, absolute water/fat content can be determined. Results: By considering calcification and interseed attenuation, and through the knowledge of water and fat mass density, accurate patient-specific implant dosimetry can be achieved with MRI-only. Conclusion: The proposed framework showed that model-based dose calculation is feasible using MRI-only state-of-the-art techniques.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TU-AB-BRA-01: Abdominal Synthetic CT Generation in Support of Liver SBRT Dose Calculation

Purpose: To demonstrate and validate a technique for generating MRI-derived synthetic CT volumes (MRCTs) in support of adaptive liver SBRT. Methods: Under IRB approval, ten hepatocellular carcinoma patients were scanned using a single MR sequence (T1 Dixon-VIBE), yielding inherently-registered water, fat, and T1-weighted images. Air-containing voxels were identified by intensity thresholding. The envelope of the anterior vertebral bodies was segmented from the fat image by fitting a shape model to vertebral body candidate voxels, then using level sets to expand the contour outward. Fuzzy-C-Means (FCM) was then used to classify each non-air voxel in the image as fat, water, bone, or marrow. Bone and marrow only were classified within the vertebral body envelope. The MRCT was created by integrating the product of the FCM class probability with the assigned class density for each voxel. The resulting MRCTs were deformably aligned with planning CTs and 2-ARC SBRT VMAT plans were optimized on the MRCT density maps. Fluence was copied onto the CT density grids and dose recalculated. Results: The MRCTs faithfully reproduced most of the features visible in the corresponding CT image volumes, with exceptions of ribs and posterior spinous processes. The liver, vertebral bodies, kidneys, spleen and cord all had median HU differences of less than 75 between MRCT and CT images. PTV D99% values had an average 0.2% difference (standard deviation: 0.46%) between calculations on MRCT and CT density grids. The maximum difference in dose to 0.1cc of the PTV was 0.25% (std:0.49%). OAR dose differences were similarly small (mean:0.03Gy, std:0.26Gy). The largest normal tissue complication percentage (NTCP) difference was 1.48% (mean:0.06%, std:0.54%). Conclusions: MRCTs from a single abdominal imaging sequence are promising for use in SBRT dose calculation. Future work will focus on extending models to better define bones in the upper abdomen. Supported by NIHR01EB016079 and NIH1L30CA199594-01.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Mongooses ( Urva auropunctata ) as reservoir hosts of Leptospira species in the United States Virgin Islands, 2019–2020

During 2019–2020, the Virgin Islands Department of Health investigated potential animal reservoirs of Leptospira spp., the bacteria that cause leptospirosis. In this cross-sectional study, we investigated Leptospira spp. exposure and carriage in the small Indian mongoose (Urva auropunctata, syn: Herpestes auropunctatus), an invasive animal species. This study was conducted across the three main islands of the U.S. Virgin Islands (USVI), which are St. Croix, St. Thomas, and St. John. We used the microscopic agglutination test (MAT), fluorescent antibody test (FAT), real-time polymerase chain reaction (lipl32 rt-PCR), and bacterial culture to evaluate serum and kidney specimens and compared the sensitivity, specificity, positive predictive value, and negative predictive value of these laboratory methods. Mongooses (n = 274) were live-trapped at 31 field sites in ten regions across USVI and humanely euthanized for Leptospira spp. testing. Bacterial isolates were sequenced and evaluated for species and phylogenetic analysis using the ppkgene. Anti-Leptospira spp. antibodies were detected in 34% (87/256) of mongooses. Reactions were observed with the following serogroups: Sejroe, Icterohaemorrhagiae, Pyrogenes, Mini, Cynopteri, Australis, Hebdomadis, Autumnalis, Mankarso, Pomona, and Ballum. Of the kidney specimens examined, 5.8% (16/270) were FAT-positive, 10% (27/274) were culture-positive, and 12.4% (34/274) were positive by rt-PCR. Of the Leptospira spp. isolated from mongooses, 25 were L. borgpetersenii, one was L. interrogans, and one was L. kirschneri. Positive predictive values of FAT and rt-PCR testing for predicting successful isolation of Leptospira by culture were 88% and 65%, respectively. The isolation and identification of Leptospira spp. in mongooses highlights the potential role of mongooses as a wildlife reservoir of leptospirosis; mongooses could be a source of Leptospira spp. infections for other wildlife, domestic animals, and humans.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Body surface area equations for physically active men and women

Abstract Objectives To improve predictive formulae for estimating body surface area (BSA) in healthy men and women using a modern three‐dimensional scanner technology. Methods Body surface areas were obtained from a convenience sample of 1267 US Marines (464 women and 803 men) using a whole body surface scanner (Size Stream SS20). The reliability of SS20 measures of total and regional BSA within participants was compared across triplicate scans. We then derived a series of formulae to estimate SS20‐measured BSA using various combinations of sex, height, and mass. We also assessed relationships between percent body fat measured by dual‐energy x‐ray absorptiometry and sex‐specific formulae errors in Marines. Results Body surface areas recorded by the SS20 were highly reliable whether measured for the total body or by region (ICC ≥ .962). Formulae estimates of BSA from sex, height, and mass were precise (root‐mean‐square deviation, 0.031 m 2 ). Errors from the Marine Corps formulae were positively associated with percent body fat for men ( p = .001) but not women ( p = .843). Conclusions Clinicians, military leaders, and researchers can use the newly developed BSA formulae for precise estimates in healthy physically active men and women. Users should be aware that height‐ and mass‐based BSA estimates are less accurate for individuals with extremely low or high percent body fat.

Looney, David P.↗
DOE OSTI2014

NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na{sup +}/H{sup +} exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Fatty acid oxidation alleviates the energy deficiency caused by the loss of MPC1 in MPC1+/− mice

Highlights: • The MPC1{sup +/−} mice model shows energy deficiency. • The deficiency caused by the loss of MPC1 alleviated by given high fat diet. • Fatty acid oxidation provides energy to sustain energy requirement. Pyruvate is a central substrate in energy metabolism, paramount to carbohydrate, fat, and amino acid catabolic and anabolic pathways. Mitochondrial pyruvate carrier 1(MPC1) is one important component of the complex that facilitates mitochondrial pyruvate import. Complete MPC1 deficiency is a serious concern, and has been shown to result in embryonic lethality in mice. The study outlined in this paper generated one mouse line with the MPC1 protein part deficiency by using the CRISPR/Cas9 system. Clinical observations, body weight and organ/tissue weight, gas exchange, cold-stimulation, blood parameters, as well as histopathology analysis were analyzed to evaluate potential physiological abnormalities caused by MPC1 deficiency. Results indicate that MPC1{sup +/−} mice experienced a change in important clinical criteria such as low body weight, decreased movement, and low body shell temperature, few adipose accumulate. The mice show significant difference in some blood parameters including apo-B100, apo-A1, HDL, glucagon, insulin. However these changes alleviated while being fed with the HFD, which provided metabolites to sustain the TCA cycle and body development. The MPC1{sup +/−} mice may employ fatty acid oxidation to meet their bioenergetic demands. This study suggests that inhibition of MPC1 activity can boost fatty acid oxidation to provide sufficient energy to the body. This work promotes further studies regarding the interplay between carbohydrate and fat metabolism.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Atf3 induction is a therapeutic target for obesity and metabolic diseases

Highlights: • Atf3 knockout mice increases body weight and impaired glucose tolerance in high fat diet fed mice. • Atf3 knockout mice increases body weight in chow diet fed aged mice. • Sulfuretin, a phytochemical Atf3 iducer, requires Atf3 expression to prevent obesity. Activating transcription factor 3 (Atf3) has been previously demonstrated to impact obesity and metabolism. However, a metabolic role of Atf3 in mice remains debatable. We investigated the role of Atf3 in mice and further investigated Atf3 expression as a therapeutic target for obesity and metabolic diseases. Atf3 knockout (KO) mice fed with a high fat diet (HFD) aggravated weight gain and impaired glucose metabolism compared to littermate control wild type (WT) mice. Atf3 KO aged mice fed with a chow diet (CD) for longer than 10 months also displayed increased body weight and fat mass compared to WT aged mice. We also assessed requirements of Atf3 in a phytochemical mediated anti-obese effect. Effect of sulfuretin, a previously known phytochemical Atf3 inducer, in counteracting weight gain and improving glucose tolerance was almost completely abolished in the absence of Atf3, indicating that Atf3 induction can be a molecular target for preventing obesity and metabolic diseases. We further identified other Atf3 small molecule inducers that exhibit inhibitory effects on lipid accumulation in adipocytes. These data highlight the role of Atf3 in obesity and further suggest the use of chemical Atf3 inducers for prevention of obesity and metabolic diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Microcapsule of sweet orange essential oil changes gut microbiota in diet-induced obese rats

Highlights: • Sweet orange essential oil (SOEO) microcapsules had weight loss effect on obese SD rats induced by high-fat diet. • SOEO microcapsules increased the relative abundance of Bifidobacterium (genus-level) in gut microbiota. • SOEO microcapsules protected gut barrier and decreased gut endotoxin levels by increasing the content of Bifidobacterium. Obesity is associated with the changes in gut microbiota. The aim of present study was to investigate the effects of sweet orange essential oil (SOEO) microcapsules on body weight and gut microbiota in obese rats induced by high-fat diet. By analyzing the body weight, fat rate and the sequence of cloned microbial small-subunit ribosomal RNA genes (16S rDNA) in rats fecal samples, we found that SOEO microcapsules decreased the body weight and increased the relative abundance of Bifidobacterium (genus-level) in gut microbiota. The analysis of endotoxin content proved that SOEO microcapsules protected gut barrier and decreased gut endotoxin levels by increasing the content of Bifidobacterium, then ameliorated low-grade inflammation, achieving the goal of losing weight. This might be the mechanism of SOEO microcapsules to lose body weight and provided a novel anti-obesity dietary supplement.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Municipal wastewater affects adipose deposition in male mice and increases 3T3-L1 cell differentiation

Trace concentration of EDs (endocrine disrupting compounds) in water bodies caused by wastewater treatment plant effluents is a recognized problem for the health of aquatic organisms and their potential to affect human health. In this paper we show that continuous exposure of male mice from early development to the adult life (140 days) to unrestricted drinking of wastewater collected from a municipal sewage treatment plant, is associated with an increased adipose deposition and weight gain during adulthood because of altered body homeostasis. In parallel, bisphenol A (BPA) at the administration dose of 5 μg/kg/body weight, shows an increasing effect on total body weight and fat mass. In vitro, a solid phase extract (SPE) of the wastewater (eTW), caused stimulation of 3T3-L1 adipocyte differentiation at dilutions of 0.4 and 1 % in the final culture medium which contained a concentration of BPA of 40 nM and 90 nM respectively. Pure BPA also promoted adipocytes differentiation at the concentration of 50 and 80 μM. BPA effect in 3T3-L1 cells was associated to the specific activation of the estrogen receptor alpha (ERα) in undifferentiated cells and the estrogen receptor beta (ERβ) in differentiated cells. BPA also activated the Peroxisome Proliferator Activated Receptor gamma (PPARγ) upregulating a minimal 3XPPARE luciferase reporter and the PPARγ-target promoter of the aP2 gene in adipose cells, while it was not effective in preadipocytes. The pure estrogen receptor agonist diethylstilbestrol (DES) played an opposite action to that of BPA inhibiting PPARγ activity in adipocytes, preventing cell differentiation, activating ERα in preadipocytes and inhibiting ERα and ERβ regulation in adipocytes. The results of this work show that the drinking of chemically-contaminated wastewater promotes fat deposition in male mice and that EDs present in sewage are likely responsible for this effect through a nuclear receptor-mediated mechanism. - Highlights: • Sewage watewaters (TW) sampled from a Municipal Treatment Sewage Plant are biologically active in mice and in vitro. • In male mice TW promotes an increase in adipose mass deposition following exposure from foetal to adult life. A similar effect is produced by BPA. • The expression of key genes of the adipose metabolism is increased in epidydimal fat both by TW and BPA. • An extract from the TW which concentrated the contained chemicals by a factor of 1000, is able to stimulate 3T3-L1 adipocyte differentiation. • The major chemicals contained in the TW, bisphenol A and nonylphenol, are able to promote adipocyte differentiation at the low environmentally relevant doses as are found in the TW.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Lentivirus-mediated CTRP6 silencing ameliorates diet-induced obesity in mice

Highlights: • The knockdown of CTRP6 reduced both body weight and white adipose tissue of mice. • CTRP6 knockdown decreased the serum TG and improved the insulin sensitivity in mice. • The knockdown of CTRP6 promoted brown adipogenesis both in mice and in adipocytes. • CTRP6 knockdown activated p38MAPK but inhibited Hh signaling pathway in adipocytes. The C1q/TNF-related protein 6 (CTRP6) is an adipokine involved in diverse biological processes. Formerly, we identified that CTRP6 regulates adipocyte differentiation, fatty acid oxidation and triglyceride accumulation in vitro. However, the effects of CTRP6 on adiposity in vivo have not yet been defined. This study aimed to confirm the involvement of CTRP6 in adipose accumulation and brown adipogenesis by intraperitoneal injection of the CTRP6-shRNA lentivirus into mice (CL mice). CL mice were significantly thinner than the control mice after feeding with a high fat diet (HFD), independent of food intake quantity. These HFD-fed CL mice displayed lower white and brown adipocyte sizes, and serum leptin levels, but an increase in serum adiponectin and insulin sensitivity relative to control mice. Additionally, the brown fat markers, such as UCP1, PRDM16, PGC1α and Cidea were found to be upregulated in the white and brown adipose tissue of the CL mice. These markers were also upregulated in a primary culture of mouse white and brown adipocytes treated with the CTRP6-shRNA lentivirus. Mechanistically, the knockdown of CTRP6 increased p38MAPK phosphorylation, but decreased expression of proteins involved in the Hedgehog signaling pathway (Sufu, Gli2 and Gli3). CTRP6 knockdown also upregulated expression of mitochondrial metabolic factors NRF-1, TFAM, CPT1 and Cyt C. Data from the current study show that CTRP6 knockdown protects against diet-induced obesity and promotes brown adipogenesis by the p38MAPK/Hh signaling pathway in conjunction with the upregulation of brown fat markers and mitochondrial metabolic factors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Phosphorus speciation analysis of fatty-acid-based feedstocks and fast pyrolysis biocrudes via gel permeation chromatography inductively coupled plasma high-resolution mass spectrometry

Renewable feedstocks, such as lignocelulosic fast pyrolysis oils and both vegetable oil and animal fats, are becoming a viable alternative to petroleum for producing high-quality renewable transportation fuels. However, the presence of phosphorus-containing compounds, mainly from phospholipids, in these renewable feedstocks is known to poison and deactivate hydrotreating catalysts during fuel production. In this work, gel permeation chromatography (GPC) combined with inductively coupled plasma high-resolution mass spectrometry (ICP-HRMS) was used to analyze feedstocks including unprocessed soybean oil, animal fat, and pyrolysis oils from red oak and milorganite to identify phosphorus species. The results have shown the presence of a wide range of different phosphorous compounds among all the samples analysed in this work. The GPC-ICP-HRMS analyses of a vegetable oil and two animal fats have shown different fingerprints based on the molecular weight of each of the samples, highlighting the structural differences among their corresponding phosphorus-containing compounds. While the presence of low-molecular-weight species, such as phospholipids, was expected, several high-molecular-weight species (MW > 10 000 Da) have been found, suggesting that high-molecular-weight micelles or liposomes might have been formed due to the high concentration of phospholipids in these samples. Results obtained through the hydroxylation of a mix of phospholipids (asolectin) and its posterior GPC-ICP-HRMS agree with this hypothesis. With respect to the lignocellulosic catalytic fast pyrolysis oil samples, the GPC-ICP-HRMS results obtained suggest that either aggregation or polymerization reactions might have occurred during the pyrolysis process, yielding phosphorus-containing compounds with an approximate molecular weight above 91 000 kDa. In addition, an aggregation phenomenom has been observed for those phosphorus species present within the fast pyrolysis oils after being stored for 3 months, especially for those pyrolysis oils contaning pre-processed feedstocks, such as milorganite.

09 BIOMASS FUELS↗
DOE OSTI2022

Distributed deep learning training using silicon photonic switched architectures

The scaling trends of deep learning models and distributed training workloads are challenging network capacities in today’s datacenters and high-performance computing (HPC) systems. We propose a system architecture that leverages silicon photonic (SiP) switch-enabled server regrouping using bandwidth steering to tackle the challenges and accelerate distributed deep learning training. In addition, our proposed system architecture utilizes a highly integrated operating system-based SiP switch control scheme to reduce implementation complexity. To demonstrate the feasibility of our proposal, we built an experimental testbed with a SiP switch-enabled reconfigurable fat tree topology and evaluated the network performance of distributed ring all-reduce and parameter server workloads. The experimental results show up to 3.6× improvements over the static non-reconfigurable fat tree. Our large-scale simulation results show that server regrouping can deliver up to 2.3× flow throughput improvement for a 2× tapered fat tree and a further 11% improvement when higher-layer bandwidth steering is employed. The collective results show the potential of integrating SiP switches into datacenters and HPC systems to accelerate distributed deep learning training.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗