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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 595 records · Page 33
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Species-specific effects of neuregulin-1β (cimaglermin alfa) on glucose handling in animal models and humans with heart failure

Neuregulin-1β is a member of the neuregulin family of growth factors and is critically important for normal development and functioning of the heart and brain. A recombinant version of neuregulin-1β, cimaglermin alfa (also known as glial growth factor 2 or GGF2) is being investigated as a possible therapy for heart failure. Previous studies suggest that neuregulin-1β stimulation of skeletal muscle increases glucose uptake and, specifically, sufficient doses of cimaglermin alfa acutely produce hypoglycemia in pigs. Since acute hypoglycemia could be a safety concern, blood glucose changes in the above pig study were further investigated. In addition, basal glucose and glucose disposal were investigated in mice. Finally, as part of standard clinical chemistry profiling in a single ascending-dose human safety study, blood glucose levels were evaluated in patients with heart failure after cimaglermin alfa treatment. A single intravenous injection of cimaglermin alfa at doses of 0.8 mg/kg and 2.6 mg/kg in mice resulted in a transient reduction of blood glucose concentrations of approximately 20% and 34%, respectively, at 2 h after the treatment compared to pre-treatment levels. Similar results were observed in diabetic mice. Treatment with cimaglermin alfa also increased blood glucose disposal following oral challenge in mice. However, no significant alterations in blood glucose concentrations were found in human heart failure patients at 0.5 and 2 h after treatment with cimaglermin alfa over an equivalent human dose range, based on body surface area. Taken together, these data indicate strong species differences in blood glucose handling after cimaglermin alfa treatment, and particularly do not indicate that this phenomenon should affect human subjects. - Highlights: • Cimaglermin alfa acutely reduced blood glucose levels in pigs, less so in mice. • Cimaglermin alfa did not reduce blood glucose levels in heart failure patients. • Effects of cimaglermin alfa on blood glucose regulation are species-dependent.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Uptake Kinetics and Trophic Transfer of Tungsten from Cabbage to a Herbivorous Animal Model

This paper builds on previous studies on military-relevant tungsten (W) to more thoroughly explore environmental pathways and bioaccumulation kinetics during direct soil exposure versus trophic transfer and elucidate its relative accumulation and speciation in different snail organs. The modeled steady-state concentration and bioaccumulation factor (BAF) of W from soil into cabbage were 302 mg/kg and 0.55, respectively. Steady-state concentrations (34 mg/kg) and BAF values (0.05) obtained for the snail directly exposed to contaminated soil were lower than trophic transfer by consumption of W-contaminated cabbage (tissue concentration of 86 mg/kg; BAF of 0.36). Thus, consumption of contaminated food is the most important pathway for W mobility in this food chain. The highest concentrations of W compartmentalization were in the snail’s hepatopancreas based on wet chemistry and synchrotron-based investigations. Chemical speciation via inductively couple plasma mass spectrometry showed a higher degree of polytungstate partitioning in the hepatopancreas relative to the rest of the body. Based on synchrotron analysis, W was incorporated into the shell matrix during exposure, particularly during the regeneration of damaged shell. Finally, this offers the potential for application of the shell as a longer-term biomonitoring and forensics tool for historic exposure.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2025

Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP(1,2) in a position elevated from the virion membrane

Abstract Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP 1,2 ) are the standard of care for Ebola virus disease (EVD). Anti-GP 1,2 mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro and are protective in a mouse model of EVD. However, their neutralization mechanism is poorly understood because they target a GP 1,2 epitope that has evaded structural characterization. Using X-ray crystallography and cryo-electron tomography of mAb 3A6 complexed with its stalk–MPER epitope, we reveal a previously undescribed mechanism in which 3A6 binds to a conformation of GP 1,2 that is lifted from the virion membrane. We further show that in both domestic guinea pig and rhesus monkey EVD models, 3A6 provides therapeutic benefit at high-viremia advanced disease stages and at the lowest dose yet demonstrated for any anti-EBOV mAb-based monotherapy. The findings reported here can guide design of next-generation highly potent anti-EBOV therapeutics and vaccines.

Science & Technology - Other Topics↗
DOE OSTI2022

Assessing rodents as carriers of pathogenic Leptospira species in the U.S. Virgin Islands and their risk to animal and public health

Leptospirosis is a global zoonotic disease caused by pathogenic bacteria of the genus Leptospira. We sought to determine if rodents in U.S. Virgin Islands (USVI) are carriers of Leptospira. In total, 140 rodents were sampled, including 112 Mus musculus and 28 Rattus rattus. A positive carrier status was identified for 64/140 (45.7%); 49 (35.0%) were positive by dark-field microscopy, 60 (42.9%) by culture, 63 (45.0%) by fluorescent antibody testing, and 61 (43.6%) by real-time polymerase chain reaction (rtPCR). Molecular typing indicated that 48 isolates were L. borgpetersenii and 3 were L. kirschneri; the remaining nine comprised mixed species. In the single culture-negative sample that was rtPCR positive, genotyping directly from the kidney identified L. interrogans. Serotyping of L. borgpetersenii isolates identified serogroup Ballum and L. kirschneri isolates as serogroup Icterohaemorrhagiae. These results demonstrate that rodents are significant Leptospira carriers and adds to understanding the ecoepidemiology of leptospirosis in USVI.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Peripheral white blood cells profile of biodegradable metal implant in mice animal model

Biocompatibility or safety of the medical device is considered important. It can be determined by blood profile examination. The aim of this study was to assess the biocompatibility of biodegradable metal implant through peripheral white blood cells (WBCs) profile approach. Forty eight male ddy mice were divided into four groups according to the materials implanted: iron wire (Fe), magnesium rod (Mg), stainless steel surgical wire (SS316L) and control with sham (K). Implants were inserted and attached onto the right femoral bone on latero-medial region. In this study, peripheral white blood cells and leukocyte differentiation were the parameters examined. The result showed that the WBCs value of all groups were decreased at the first day after implantation, increased at the 10th day and continued increasing at the 30th day of observation, except Mg group which has decreased. Neutrophil, as an inflammatory cells, was increased at the early weeks and decreased at the day-30 after surgery in all groups. Despite, these values during the observation were still within the normal range. As a conclus ion, biodegradable metal implants lead to an inflammatory reaction, with no adverse effect on WBC value found.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Scaling animal to human biodistribution of the radiopharmaceutical [68Ga]Ga-PSMA-HBED-CC

The radiotracer called {sup 68}Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]Ga-PSMA-HBED-CC) is a novel radiophar-maceutical for the detection of prostate cancer lesions by positron emission tomography (PET) imaging. Setting up a cost-effective manual synthesis of this radiotracer and making its clinical translation in Colombia will require two important elements: the evaluation of the procedure to yield a consistent product, meeting standards of radio-chemical purity and low toxicity and then, the evaluation of the radiation dosimetry. In this paper a protocol to extrapolate the biokinetic model made in normal mice to humans by using the computer software for internal dose assessment OLINDA/EXM® is presented as an accurate and standardized method for the calculation of radiation dosimetry estimates.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

A small long-life acoustic transmitter for studying the behavior of aquatic animals

The lack of stronger acoustic signal, longer service life and smaller size from off-the-shelf transmitters has precluded intensive research for environmental monitoring of certain species using acoustic telemetry techniques. In this study we developed a small long-life acoustic transmitter with the length of approximately 24.2 mm, the diameter of approximately 5.0 mm, and the dry weight of approximately 0.72 g. The new transmitter can generate an acoustic signal at selectable source level between 159 and 163 dB re 1 µPa at 1 m. The new acoustic transmitter has an operation lifetime up to a year or longer at a pulse rate interval of 15 seconds, and also has a signal detection range up to at least 500 meters that enhances detection probability in a quiet environment. Furthermore, the new technology makes long-term acoustic telemetry studies of small fish possible and is being deployed for long-term tracking of juvenile sturgeon.

47 OTHER INSTRUMENTATION↗
DOE OSTI2017

Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals

Significance Protein expression using mRNA has the potential to transform many areas of life science research and affect the prevention, detection, and treatment of disease. However, realizing this potential requires the development of readily accessible, efficacious, and safe delivery systems that can functionally deliver mRNA to cells in culture and in vivo. A class of materials developed for mRNA delivery is described that operates through an unprecedented self-immolation mechanism. These materials are accessed in two steps through an organocatalytic oligomerization. They noncovalently complex, protect, deliver, and release mRNA with >99% transfection efficiency in cultured cells and with robust protein expression in mice using multiple routes of administration. This mRNA delivery technology should be broadly applicable to numerous research and therapeutic applications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Use of carbon monoxide and hydrogen by a bacteria-animal symbiosis from seagrass sediments

The gutless marine worm Olavius algarvensis lives in symbiosis with chemosynthetic bacteria that provide nutrition by fixing carbon dioxide (CO 2 ) into biomass using reduced sulfur compounds as energy sources. A recent metaproteomic analysis of the O. algarvensis symbiosis indicated that carbon monoxide (CO) and hydrogen (H 2 ) might also be used as energy sources. We provide direct evidence that the O. algarvensis symbiosis consumes CO and H 2 . Single cell imaging using nanoscale secondary ion mass spectrometry revealed that one of the symbionts, the γ3-symbiont, uses the energy from CO oxidation to fix CO 2 . Pore water analysis revealed considerable in-situ concentrations of CO and H 2 in the O. algarvensis environment, Mediterranean seagrass sediments. Pore water H 2 concentrations (89-2147 nM) were up to two orders of magnitude higher than in seawater, and up to 36-fold higher than previously known from shallow-water marine sediments. Pore water CO concentrations (17-51 nM) were twice as high as in the overlying seawater (no literature data from other shallow-water sediments are available for comparison). Ex-situ incubation experiments showed that dead seagrass rhizomes produced large amounts of CO. Lastly, CO production from decaying plant material could thus be a significant energy source for microbial primary production in seagrass sediments.

54 ENVIRONMENTAL SCIENCES↗