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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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All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Engineered Glucose Oxidase‐Carbon Nanotube Conjugates for Tissue‐Translatable Glucose Nanosensors

Abstract Continuous and non‐invasive glucose monitoring and imaging is important for disease diagnosis, treatment, and management. However, glucose monitoring remains a technical challenge owing to the dearth of tissue‐transparent glucose sensors. In this study, we present the development of near‐infrared fluorescent single‐walled carbon nanotube (SWCNT) based nanosensors directly functionalized with glucose oxidase (GOx) capable of immediate and reversible glucose imaging in biological fluids and tissues. We prepared GOx‐SWCNT nanosensors by facile sonication of SWCNT with GOx in a manner that—surprisingly—does not compromise the ability of GOx to detect glucose. Importantly, we find by using denatured GOx that the fluorescence modulation of GOx‐SWCNT is not associated with the catalytic oxidation of glucose but rather triggered by glucose‐GOx binding. Leveraging the unique response mechanism of GOx‐SWCNT nanosensors, we developed catalytically inactive apo‐GOx‐SWCNT that enables both sensitive and reversible glucose imaging, exhibiting a ΔF/F 0 of up to 40 % within 1 s of exposure to glucose without consuming the glucose analyte. We finally demonstrate the potential applicability of apo‐GOx‐SWCNT in biomedical applications by glucose quantification in human plasma and glucose imaging in mouse brain slices.

Chemistry↗
DOE OSTI2023

Whole‐Cell MALDI‐ToF MS Coupled with Untargeted Metabolomics Facilitates Investigations of Microbial Chemical Interactions

Abstract The emergence of drug‐resistant pathogens necessitates the development of new countermeasures. In this regard, the introduction of probiotics to directly attack or competitively exclude pathogens presents a useful strategy. Application of this approach requires an understanding of how a probiotic and its target pathogen interact. A key means of probiotic‐pathogen interaction involves the production of small molecules called natural products (NPs). Here, we report the use of whole‐cell matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐ToF) mass spectrometry to characterize NP production by candidate probiotics (mouse airway microbiome isolates) when co‐cultured with the respiratory pathogen Burkholderia . We found that a Bacillus velezensis strain inhibits growth of and elicits NP production by Burkholderia thailandensis . Dereplication of known NPs detected in the metabolome of this B. velezensis strain suggests that a previously unannotated bioactive compound is involved. Thus, we present the use of whole‐cell MALDI as a broadly applicable method for screening the NP composition of microbial co‐cultures; this can be combined with other ‐omics methods to characterize probiotic‐pathogen and other microbe‐microbe interactions.

Aiosa, Nicole↗
DOE OSTI2024

Distinct cellular expression and subcellular localization of Kv2 voltage‐gated K + channel subtypes in dorsal root ganglion neurons conserved between mice and humans

Abstract The distinct organization of Kv2 voltage‐gated potassium channels on and near the cell body of brain neurons enables their regulation of action potentials and specialized membrane contact sites. Somatosensory neurons have a pseudounipolar morphology and transmit action potentials from peripheral nerve endings through axons that bifurcate to the spinal cord and the cell body within ganglia including the dorsal root ganglia (DRG). Kv2 channels regulate action potentials in somatosensory neurons, yet little is known about where Kv2 channels are located. Here, we define the cellular and subcellular localization of the Kv2 paralogs, Kv2.1 and Kv2.2, in DRG somatosensory neurons with a panel of antibodies, cell markers, and genetically modified mice. We find that relative to spinal cord neurons, DRG neurons have similar levels of detectable Kv2.1 and higher levels of Kv2.2. In older mice, detectable Kv2.2 remains similar, while detectable Kv2.1 decreases. Both Kv2 subtypes adopt clustered subcellular patterns that are distinct from central neurons. Most DRG neurons co‐express Kv2.1 and Kv2.2, although neuron subpopulations show preferential expression of Kv2.1 or Kv2.2. We find that Kv2 protein expression and subcellular localization are similar between mouse and human DRG neurons. We conclude that the organization of both Kv2 channels is consistent with physiological roles in the somata and stem axons of DRG neurons. The general prevalence of Kv2.2 in DRG as compared to central neurons and the enrichment of Kv2.2 relative to detectable Kv2.1 in older mice, proprioceptors, and axons suggest more widespread roles for Kv2.2 in DRG neurons.

Neurosciences & Neurology↗
DOE OSTI2023

Treatment of cholinergic‐induced status epilepticus with polytherapy targeting GABA and glutamate receptors

Abstract Despite new antiseizure medications, the development of cholinergic‐induced refractory status epilepticus (RSE) continues to be a therapeutic challenge as pharmacoresistance to benzodiazepines and other antiseizure medications quickly develops. Studies conducted by Epilepsia . 2005;46:142 demonstrated that the initiation and maintenance of cholinergic‐induced RSE are associated with trafficking and inactivation of gamma‐aminobutyric acid A receptors (GABA A R) thought to contribute to the development of benzodiazepine pharmacoresistance. In addition, Dr. Wasterlain's laboratory reported that increased N‐methyl‐ d ‐aspartate receptors (NMDAR) and alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPAR) contribute to enhanced glutamatergic excitation ( Neurobiol Dis . 2013;54:225; Epilepsia . 2013;54:78). Thus, Dr. Wasterlain postulated that targeting both maladaptive responses of reduced inhibition and increased excitation that is associated with cholinergic‐induced RSE should improve therapeutic outcome. We currently review studies in several animal models of cholinergic‐induced RSE that demonstrate that benzodiazepine monotherapy has reduced efficacy when treatment is delayed and that polytherapy with drugs that include a benzodiazepine (eg midazolam and diazepam) to counter loss of inhibition, concurrent with an NMDA antagonist (eg ketamine) to reduce excitation provide improved efficacy. Improved efficacy with polytherapy against cholinergic‐induced seizure is demonstrated by reduction in (1) seizure severity, (2) epileptogenesis, and (3) neurodegeneration compared with monotherapy. Animal models reviewed include pilocarpine‐induced seizure in rats, organophosphorus nerve agent (OPNA)‐induced seizure in rats, and OPNA‐induced seizure in two mouse models: (1) carboxylesterase knockout (Es1 −/− ) mice which, similarly to humans, lack plasma carboxylesterase and (2) human acetylcholinesterase knock‐in carboxylesterase knockout (KIKO) mice. We also review studies showing that supplementing midazolam and ketamine with a third antiseizure medication (valproate or phenobarbital) that targets a nonbenzodiazepine site rapidly terminates RSE and provides further protection against cholinergic‐induced SE. Finally, we review studies on the benefits of simultaneous compared with sequential drug treatments and the clinical implications that lead us to predict improved efficacy of early combination drug therapies. The data generated from seminal rodent studies of efficacious treatment of cholinergic‐induced RSE conducted under Dr. Wasterlain's guidance suggest that future clinical trials should treat the inadequate inhibition and temper the excess excitation that characterize RSE and that early combination therapies may provide improved outcome over benzodiazepine monotherapy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Chemical composition of cold‐pressed blackberry seed flour extract and its potential health‐beneficial properties

Abstract The blackberry seed flour was cold‐extracted using 50% acetone and examined for its phytochemical composition and health‐beneficial properties including in vitro gut microbiota modulatory, free radical scavenging, anti‐inflammatory, and antiproliferative capacities. Among identified thirteen components of blackberry seed flour extract through UHPLC‐MS analysis, sanguiin H6 was the primary component and followed by ellagic acid and pedunculagin. For health‐beneficial properties, the blackberry seed flour extract increased the total number of gut bacteria and shifted the abundance of specific bacterial phylum, family, or genus. The extract had RDSC, ORAC, HOSC, and ABTS •+ scavenging capacities of 362, 304, 2,531, and 267 μmol Trolox equivalents (TE)/g, respectively. In addition, the blackberry seed flour extract showed capacities for anti‐inflammation and antiproliferation by suppressing LPS induced IL‐1β mRNA expressions in the cultured J774A.1 mouse macrophages and the proliferation of LNCaP prostate cancer cells. The results suggest potential health benefits and further utilization of blackberry seed flour as functional foods.

Choe, Uyory↗
DOE OSTI2023

Macrophage-derived MLKL in alcohol-associated liver disease: Regulation of phagocytosis

Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays a role in intracellular vesicle trafficking that is critical for regulating liver inflammation and injury in alcohol-associated liver disease (ALD). Although receptor interacting protein kinase 3 (Rip3) -/- mice are completely protected from ethanol-induced liver injury, Mlkl -/- mice are only partially protected. Therefore, we hypothesized that cell-specific functions of MLKL may contribute to ethanol-induced injury. Bone marrow transplants between Mlkl -/- mice and littermates were conducted to distinguish the role of myeloid versus nonmyeloid Mlkl in the Gao-binge model of ALD. Ethanol-induced hepatic injury, steatosis, and inflammation were exacerbated in Mlkl -/- →wild-type (WT) mice, whereas Mlkl deficiency in nonmyeloid cells (WT→Mlkl -/- ) had no effect on Gao-binge ethanol-induced injury. Importantly, Mlkl deficiency in myeloid cells exacerbated ethanol-mediated bacterial burden and accumulation of immune cells in livers. Mechanistically, challenging macrophages with lipopolysaccharide (LPS) induced signal transducer and activator of transcription 1–mediated expression and phosphorylation of MLKL, as well as translocation and oligomerization of MLKL to intracellular compartments, including phagosomes and lysosomes but not plasma membrane. Importantly, pharmacological or genetic inhibition of MLKL suppressed the phagocytic capability of primary mouse Kupffer cells (KCs) at baseline and in response to LPS with/without ethanol as well as peripheral monocytes isolated from both healthy controls and patients with alcohol-associated hepatitis. Further, in vivo studies revealed that KCs of Mlkl -/- mice phagocytosed fewer bioparticles than KCs of WT mice. Together, these data indicate that myeloid MLKL restricts ethanol-induced liver inflammation and injury by regulating hepatic immune cell homeostasis and macrophage phagocytosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Physical Models from Physical Templates Using Biocompatible Liquid Crystal Elastomers as Morphologically Programmable Inks For 3D Printing

Advanced manufacturing has received considerable attention as a tool for the fabrication of cell scaffolds however, finding ideal biocompatible and biodegradable materials that fit the correct parameters for 3D printing and guide cells to align remain a challenge. Herein, a photocrosslinkable smectic-A (Sm-A) liquid crystal elastomer (LCE) designed for 3D printing is presented, that promotes cell proliferation but most importantly induces cell anisotropy. The LCE-based bio-ink allows the 3D duplication of a highly complex brain structure generated from an animal model. Vascular tissue models are generated from fluorescently stained mouse tissue spatially imaged using confocal microscopy and subsequently processed to create a digital 3D model suitable for printing. The 3D structure is reproduced using a Digital Light Processing (DLP) stereolithography (SLA) desktop 3D printer. Synchrotron Small-Angle X-ray Diffraction (SAXD) data reveal a strong alignment of the LCE layering within the struts of the printed 3D scaffold. The resultant anisotropy of the LCE struts is then shown to direct cell growth. This study offers a simple approach to produce model tissues built within hours that promote cellular alignment.

3D cell culture↗
DOE OSTI2025

Visualizing and analyzing 3D biomolecular structures using Mol* at RCSB.org: Influenza A H5N1 virus proteome case study

The easiest and often most useful way to work with experimentally determined or computationally predicted structures of biomolecules is by viewing their three-dimensional (3D) shapes using a molecular visualization tool. Mol* was collaboratively developed by RCSB Protein Data Bank (RCSB PDB, RCSB.org) and Protein Data Bank in Europe (PDBe, PDBe.org) as an open-source, web-based, 3D visualization software suite for examination and analyses of biostructures. It is capable of displaying atomic coordinates and related experimental data of biomolecular structures together with a variety of annotations, facilitating basic and applied research, training, education, and information dissemination. Across RCSB.org, the RCSB PDB research-focused web portal, Mol* has been implemented to support single-mouse-click atomic-level visualization of biomolecules (e.g., proteins, nucleic acids, carbohydrates) with bound cofactors, small-molecule ligands, ions, water molecules, or other macromolecules. RCSB.org Mol* can seamlessly display 3D structures from various sources, allowing structure interrogation, superimposition, and comparison. Using influenza A H5N1 virus as a topical case study of an important pathogen, we exemplify how Mol* has been embedded within various RCSB.org tools—allowing users to view polymer sequence and structure-based annotations integrated from trusted bioinformatics data resources, assess patterns and trends in groups of structures, and view structures of any size and compositional complexity. In addition to being linked to every experimentally determined biostructure and Computed Structure Model made available at RCSB.org, Standalone Mol* is freely available for visualizing any atomic-level or multi-scale biostructure at rcsb.org/3d-view.

3D biostructure↗
DOE OSTI2022

Wogonoside attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis through SOCS1 / P53 / SLC7A11 pathway

Abstract Wogonoside (WG) is a flavonoid chemical component extracted from Scutellaria baicalensis, which exerts therapeutic effects on liver diseases. Ferroptosis, a novel form of programmed cell death, regulates diverse physiological/pathological processes. In this study, we attempted to investigate a novel mechanism by which WG mitigates liver fibrosis by inducing ferroptosis in hepatic stellate cells (HSCs). A CCl 4 ‐induced mouse liver fibrosis model and a rat HSC line were employed for in vivo and in vitro experiments, both treated with WG. Firstly, the levels of the fibrotic markers α‐smooth muscle actin (α‐SMA) and α1(I)collagen (COL1α1) were effectively decreased by WG in CCl 4 ‐induced mice and HSC‐T6 cells. Additionally, mitochondrial condensation and mitochondrial ridge breakage were observed in WG‐treated HSC‐T6 cells. Furthermore, ferroptotic events including depletion of SLC7A11, GPX4 and GSH, and accumulation of iron, ROS and MDA were discovered in WG‐treated HSC‐T6 cells. Intriguingly, these ferroptotic events did not appear in hepatocytes or macrophages. WG‐elicited HSC ferroptosis and ECM reduction were dramatically abrogated by ferrostatin‐1 (Fer‐1), a ferroptosis inhibitor. Importantly, our results confirm that SOCS1/P53/SLC7A11 is a signaling pathway which promotes WG attenuation of liver fibrosis. On the contrary, WG mitigated liver fibrosis and inducted HSC‐T6 cell ferroptosis were hindered by SOCS1 siRNA and pifithrin‐α (PFT‐α). These findings demonstrate that SOCS1/P53/SLC7A11‐mediated HSC ferroptosis is associated with WG alleviating liver fibrosis, which provides a new clue for the treatment of liver fibrosis.

Liu, Guofang↗
DOE OSTI2021

Integrated laser ablation-dropletProbe-mass spectrometry for absolute drug quantitation, metabolite detection, and distribution in tissue

Rationale: Spatially resolved and accurate quantitation of drug-related compounds in tissue is a much-needed capability in drug discovery research. In this work, application of an integrated laser ablation-dropletProbe-mass spectrometry surface sampling system (LADP-MS) is reported, which achieved absolute quantitation of propranolol measured from <500 × 500 μm thin tissue samples. Methods: Mouse liver and kidney thin tissue sections were coated with parylene C and analyzed for propranolol by a laser ablation/liquid extraction workflow. Non-coated adjacent sections were microdissected for validation and processed using standard bulk tissue extraction protocols. High-performance liquid chromatography with positive ion mode electrospray ionization tandem mass spectrometry was applied to detect the drug and its metabolites. Results: Absolute propranolol concentration in ~500 × 500 μm tissue regions measured by the two methods agreed within ±8% and had a relative standard deviation within ±17%. Quantitation down to ~400 × 400 μm tissue regions was shown, and this resolution was also used for automated mapping of propranolol and phase II hydroxypropranolol glucuronide metabolites in kidney tissue. Conclusions: This study exemplifies the capabilities of integrated laser ablation-dropletProbe-mass spectrometry (LADP-MS) for high resolution absolute drug quantitation analysis of thin tissue sections. This capability will be valuable for applications needing to quantitatively understand the spatial distribution of small molecules in tissue.

47 OTHER INSTRUMENTATION↗
DOE OSTI2020

Unique features and emerging in vitro models of human placental development

Abstract Background The placenta is an essential organ for the normal development of mammalian fetuses. Most of our knowledge on the molecular mechanisms of placental development has come from the analyses of mice, especially histopathological examination of knockout mice. Choriocarcinoma and immortalized cell lines have also been used for basic research on the human placenta. However, these cells are quite different from normal trophoblast cells. Methods In this review, we first provide an overview of mouse and human placental development with particular focus on the differences in the anatomy, transcription factor networks, and epigenetic characteristics between these species. Next, we discuss pregnancy complications associated with abnormal placentation. Finally, we introduce emerging in vitro models to study the human placenta, including human trophoblast stem (TS) cells, trophoblast and endometrium organoids, and artificial embryos. Main findings The placental structure and development differ greatly between humans and mice. The recent establishment of human TS cells and trophoblast and endometrial organoids enhances our understanding of the mechanisms underlying human placental development. Conclusion These in vitro models will greatly advance our understanding of human placental development and potentially contribute to the elucidation of the causes of infertility and other pregnancy complications.

Shibata, Shun↗
DOE OSTI2021

Development of an optimized and scalable method for isolation of umbilical cord blood-derived small extracellular vesicles for future clinical use

Abstract Extracellular vesicles (EV) are a promising therapeutic tool in regenerative medicine. These particles were shown to accelerate wound healing, through delivery of regenerative mediators, such as microRNAs. Herein we describe an optimized and upscalable process for the isolation of EV smaller than 200 nm (sEV), secreted by umbilical cord blood mononuclear cells (UCB-MNC) under ischemic conditions and propose quality control thresholds for the isolated vesicles, based on the thorough characterization of their protein, lipid and RNA content. Ultrafiltration and size exclusion chromatography (UF/SEC) optimized methodology proved superior to traditional ultracentrifugation (UC), regarding production time, standardization, scalability, and vesicle yield. Using UF/SEC, we were able to recover approximately 400 times more sEV per mL of media than with UC, and upscaling this process further increases EV yield by about 3-fold. UF/SEC-isolated sEV display many of the sEV/exosomes classical markers and are enriched in molecules with anti-inflammatory and regenerative capacity, such as hemopexin and miR-150. Accordingly, treatment with sEV promotes angiogenesis and extracellular matrix remodeling, in vitro. In vivo, UCB-MNC-sEV significantly accelerate skin regeneration in a mouse model of delayed wound healing. The proposed isolation protocol constitutes a significant improvement compared to UC, the gold-standard in the field. Isolated sEV maintain their regenerative properties, whereas downstream contaminants are minimized. The use of UF/SEC allows for the standardization and upscalability required for mass production of sEV to be used in a clinical setting.

Cardoso, Renato M. S.↗
DOE OSTI2022

Development and Application of DropletProbe Mass Spectrometry for Examining Biodistribution of Therapeutics

dropletProbe mass spectrometry is a novel technique for molecular characterization of surfaces. It can be used for rapid ex vivo analysis of therapeutics from thin animal tissue sections and has been shown to improve understanding of a drug’s absorption, distribution, metabolism and excretion (ADME) properties. Here, we describe the tissue distribution analysis of diclofenac from a dosed whole-body mouse thin tissue section using a dropletProbe mass spectrometry system.

Chen, Bingming↗
DOE OSTI2022

Fully Integrated Ultra-thin Intraoperative Micro-imager for Cancer Detection Using Upconverting Nanoparticles

Abstract Purpose Intraoperative detection and removal of microscopic residual disease (MRD) remain critical to the outcome of cancer surgeries. Today’s minimally invasive surgical procedures require miniaturization and surgical integration of highly sensitive imagers to seamlessly integrate into the modern clinical workflow. However, current intraoperative imagers remain cumbersome and still heavily dependent on large lenses and rigid filters, precluding further miniaturization and integration into surgical tools. Procedures We have successfully engineered a chip-scale intraoperative micro-imager array—without optical filters or lenses—integrated with lanthanide-based alloyed upconverting nanoparticles (aUCNPs) to achieve tissue imaging using a single micro-chip. This imaging platform is able to leverage the unique optical properties of aUCNPs (long luminescent lifetime, high-efficiency upconversion, no photobleaching) by utilizing a time-resolved imaging method to acquire images using a 36-by-80-pixel, 2.3 mm $$\times$$ × 4.8 mm silicon-based electronic imager micro-chip, that is, less than 100-µm thin. Each pixel incorporates a novel architecture enabling automated background measurement and cancellation. We have validated the performance, spatial resolution, and the background cancellation scheme of the imaging platform, using resolution test targets and mouse prostate tumor sample intratumorally injected with aUCNPs. To demonstrate the ability to image MRD, or tumor margins, we evaluated the imaging platform in visualizing a single-cell thin section of the injected prostate tumor sample. Results Tested on USAF resolution targets, the imager is able to achieve a resolution of 71 µm. We have also demonstrated successful background cancellation, achieving a signal-to-background ratio of 8 when performing ex vivo imaging on aUCNP-injected prostate tumor sample, improved from originally 0.4. The performance of the imaging platform on single-cell layer sections was also evaluated and the sensor achieved a signal-to-background ratio of 4.3 in resolving cell clusters with sizes as low as 200 cells. Conclusion The imaging system proposed here is a scalable chip-scale ultra-thin alternative for bulky conventional intraoperative imagers. Its novel pixel architecture and background correction scheme enable visualization of microscopic-scale residual disease while remaining completely free of lenses and filters, achieving an ultra-miniaturized form factor—critical for intraoperative settings.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Development of 52Mn Labeled Trastuzumab for Extended Time Point PET Imaging of HER2

Abstract Purpose Due to their long circulation time in the blood, monoclonal antibodies (mAbs) such as trastuzumab, are usually radiolabeled with long-lived positron emitters for the development of agents for Positron Emission Tomography (PET) imaging. Manganese-52 ( 52 Mn, t 1/2 = 5.6 d, β + = 29.6%, E(β ave ) = 242 keV) is suitable for imaging at longer time points providing a complementary technique to Zirconium-89 ( 89 Zr, t 1/2 = 3.3 d, β + = 22.7%, E(β ave ) = 396 keV)) because of its long half-life and low positron energy. To exploit these properties, we aimed to investigate suitable bifunctional chelators that could be readily conjugated to antibodies and labeled with 52 Mn under mild conditions using trastuzumab as a proof-of-concept. Procedures Trastuzumab was incubated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), 1-Oxa-4,7,10-tetraazacyclododecane-5-S-(4-isothiocyantobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A), and 3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA) at a tenfold molar excess. The immunoconjugates were purified, combined with [ 52 Mn]MnCl 2 at different ratios, and the labeling efficiency was assessed by iTLC. The immunoreactive fraction of the radiocomplex was determined through a Lindmo assay. Cell studies were conducted in HER2 + (BT474) and HER2- (MDA-MB-468) cell lines followed by in vivo studies. Results Trastuzumab-Oxo-DO3A was labeled within 30 min at 37 °C with a radiochemical yield (RCY) of 90 ± 1.5% and with the highest specific activity of the chelators investigated of 16.64 MBq/nmol. The labeled compound was purified with a resulting radiochemical purity of > 98% and retained a 67 ± 1.2% immunoreactivity. DOTA and PCTA immunoconjugates resulted in < 50 ± 2.5% (RCY) with similar specific activity. Mouse serum stability studies of [ 52 Mn]Mn-Oxo-DO3A-trastuzumab showed 95% intact complex for over 5 days. Cell uptake studies showed higher uptake in HER2 + (12.51 ± 0.83% /mg) cells compared to HER2- (0.85 ± 0.10%/mg) cells. PET images of mice bearing BT474 tumors showed high tumor uptake that was consistent with the biodistribution (42.02 ± 2.16%ID/g, 14 d) compared to MDA-MB-468 tumors (2.20 ± 0.80%ID/g, 14 d). Additionally, both models exhibited low bone uptake of < 1% ID/g. Conclusion The bifunctional chelator p-SCN-Bn-Oxo-DO3A is promising for the development of 52 Mn radiopharmaceuticals as it was easily conjugated, radiolabeled at mild conditions, and illustrated stability for a prolonged duration both in vitro and in vivo . High-quality PET/CT images of [ 52 Mn]Mn-Oxo-DO3A-trastuzumab were obtained 14 d post-injection. This study illustrates the potential of [ 52 Mn]Mn-Oxo-DO3A for the evaluation of antibodies using PET imaging.

Omweri, James M.↗
DOE OSTI2022

Elamipretide effects on the skeletal muscle phosphoproteome in aged female mice

The age-related decline in skeletal muscle mass and function is known as sarcopenia. Sarcopenia progresses based on complex processes involving protein dynamics, cell signaling, oxidative stress, and repair. We have previously found that 8-week treatment with elamipretide improves skeletal muscle function, reverses redox stress, and restores protein S-glutathionylation changes in aged female mice. This study tested whether 8-week treatment with elamipretide also affects global phosphorylation in skeletal muscle consistent with functional improvements and S-glutathionylation. Using female 6–7-month-old mice and 28–29-month-old mice, we found that phosphorylation changes did not relate to S-glutathionylation modifications, but that treatment with elamipretide did partially reverse age-related changes in protein phosphorylation in mouse skeletal muscle.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Crystal misorientation correlates with hardness in tooth enamels

The multi-scale hierarchical structure of tooth enamel enables it to withstand a lifetime of damage without catastrophic failure. While many previous studies have investigated structure-function relationships in enamel, the effects of crystal misorientation on mechanical performance have not been assessed. To address this issue, in the present study, we review previously published polarization-dependent imaging contrast (PIC) maps of mouse and human enamel, and parrotfish enameloid, in which crystal orientations were measured and displayed in every 60-nm-pixel. By combining those previous results with the PIC maps of sheep enamel presented here we discovered that, in all enamel(oid)s, adjacent crystals are slightly misoriented, with misorientation angles in the 0°-30° range, and mean 2°-8°. Within this limited range, misorientation is positively correlated with literature hardness values, demonstrating an important structure-property relation, not previously identified. At greater misorientation angles 8°30°, this correlation is expected to reverse direction, but data from different non-enamel systems, with more diverse crystal misorientations, are required to determine if and where this occurs.

36 MATERIALS SCIENCE↗