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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 451 records · Page 25
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Metabolic brain networks in aging and preclinical Alzheimer's disease

Metabolic brain networks can provide insight into the network processes underlying progression from healthy aging to Alzheimer's disease. We explore the effect of two Alzheimer's disease risk factors, amyloid-β and ApoE ε4 genotype, on metabolic brain networks in cognitively normal older adults (N = 64, ages 69–89) compared to young adults (N = 17, ages 20–30) and patients with Alzheimer's disease (N = 22, ages 69–89). Subjects underwent MRI and PET imaging of metabolism (FDG) and amyloid-β (PIB). Normal older adults were divided into four subgroups based on amyloid-β and ApoE genotype. Metabolic brain networks were constructed cross-sectionally by computing pairwise correlations of metabolism across subjects within each group for 80 regions of interest. We found widespread elevated metabolic correlations and desegregation of metabolic brain networks in normal aging compared to youth and Alzheimer's disease, suggesting that normal aging leads to widespread loss of independent metabolic function across the brain. Amyloid-β and the combination of ApoE ε4 led to less extensive elevated metabolic correlations compared to other normal older adults, as well as a metabolic brain network more similar to youth and Alzheimer's disease. This could reflect early progression towards Alzheimer's disease in these individuals. Altered metabolic brain networks of older adults and those at the highest risk for progression to Alzheimer's disease open up novel lines of inquiry into the metabolic and network processes that underlie normal aging and Alzheimer's disease.

Neurosciences & Neurology↗
DOE OSTI2023

Multivariate chemogenomic screening prioritizes new macrofilaricidal leads

Development of direct acting macrofilaricides for the treatment of human filariases is hampered by limitations in screening throughput imposed by the parasite life cycle. In vitro adult screens typically assess single phenotypes without prior enrichment for chemicals with antifilarial potential. We developed a multivariate screen that identified dozens of compounds with submicromolar macrofilaricidal activity, achieving a hit rate of >50% by leveraging abundantly accessible microfilariae. Adult assays were multiplexed to thoroughly characterize compound activity across relevant parasite fitness traits, including neuromuscular control, fecundity, metabolism, and viability. Seventeen compounds from a diverse chemogenomic library elicited strong effects on at least one adult trait, with differential potency against microfilariae and adults. Our screen identified five compounds with high potency against adults but low potency or slow-acting microfilaricidal effects, at least one of which acts through a novel mechanism. We show that the use of microfilariae in a primary screen outperforms model nematode developmental assays and virtual screening of protein structures inferred with deep learning. These data provide new leads for drug development, and the high-content and multiplex assays set a new foundation for antifilarial discovery.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Early exposure to thirdhand cigarette smoke affects body mass and the development of immunity in mice

Thirdhand smoke (THS) is the fraction of cigarette smoke that persists in indoor environments after smoking. We investigated the effects of neonatal and adult THS exposure on bodyweight and blood cell populations in C57BL/6 J mice. At the end of neonatal exposure, THS-treated male and female mice had significantly lower bodyweight than their respective control mice. However, five weeks after neonatal exposure ended, THS-treated mice weighed the same as controls. In contrast, adult THS exposure did not change bodyweight of mice. On the other hand, both neonatal and adult THS exposure had profound effects on the hematopoietic system. Fourteen weeks after neonatal THS exposure ended, eosinophil number and platelet volume were significantly higher, while hematocrit, mean cell volume, and platelet counts were significantly lower compared to control. Similarly, adult THS exposure also decreased platelet counts and increased neutrophil counts. Moreover, both neonatal and adult THS exposure caused a significant increase in percentage of B-cells and significantly decreased percentage of myeloid cells. Our results demonstrate that neonatal THS exposure decreases bodyweight and that THS exposure induces persistent changes in the hematopoietic system independent of age at exposure. These results also suggest that THS exposure may have adverse effects on human health.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Suggested reference values for regional blood volumes in children and adolescents

Estimates of regional blood volumes (BVs) in humans are needed in dosimetric models of radionuclides and radiopharmaceuticals that decay in the circulation to a significant extent. These values are also needed to refine models of tissue elemental composition in computational human phantoms of both patients and exposed members of the general public. The International Commission on Radiological Protection (ICRP) in its Publication 89 provides reference values for total blood content in the full series of their reference individuals, to include the male and female newborn, 1 year-old, 5 year-old, 10 year-old, 15 year-old, and adult. Furthermore, Publication 89 provides reference values for the percentage distribution of total blood volume in 27 different blood-filled organs and tissues of the reference adult male and adult female. However, no similar distribution values are provided for non-adults. The goal of the present paper is to present a volumetric scaling methodology to derive these values for the same organs and tissues at ages younger than the reference adult. Finally, literature data on organ-specific vascular growth in the brain, kidneys, and skeletal tissues are also considered.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Correlation between Toluene Exposure and Toxicity Effects of Toluene on Drosophila Melanogaster Fecundity and Offspring Survivability

Toluene is a volatile organic compound that is a common indoor contaminant. According to the U.S. Department of Health and Human Services, chronic toluene exposure negatively affects organ systems, such as nervous and respiratory, and acts as a fetotoxic agent in the development of humans. Toluene exposure causes damage to human myelin sheaths, thus we propose that damage to the fly nervous system will be similar to that seen in humans exposed to toluene. Our ultimate goal is to determine the effects of toluene exposure on developmental and neuronal processes in D. melanogaster . In this first phase, we hypothesize that toluene‐exposed adults, at the interpolated Lethal Exposure (LE 50 ), will demonstrate decreased fecundity and that offspring from toluene‐exposed females will have decreased survivability from the egg to adult stage. We developed a continuous flow system that delivers known concentrations of gaseous toluene to populations of D. melanogaster . Ten to twenty adult female flies per trial were exposed for 24 hours to known concentrations of toluene. Surviving females were collected, counted and mated to non‐exposed adult males. The toluene‐exposed females were placed on a colored agar plate to lay eggs for 24 hours. Eggs were counted to determine fecundity (number of eggs produced by a single female fly). Survivability of eggs to later life stages, was measured by counting number of larvae, pupae, and adults divided by number eggs, larvae, and pupae respectively. The interpolated LE 50 of gaseous toluene was between 1000 and 1500 ppm after 24‐hour exposure. Fecundity of toluene‐exposed females decreased by approximately 50% when compared to airexposed females. The survivability of offspring of air‐exposed flies from egg to larval stages was 84% higher than published studies. We observed that larval eclosure from eggs laid by toluene‐exposed females was 35–50% higher on days 1 and 2 when compared to larval eclosure from eggs of air‐exposed exposed females. On days 3–6 the eclosure rate was relatively similar. These data showed toluene's effects on fecundity and survivability were measurable, however, additional replicates are in progress to fully assess the life table characteristics of offspring of toluene‐exposed female flies. Further studies will focus on toluene's effect on nervous and reproductive organs of fruit flies, along with a study on the mutagenic effects of toluene on fly DNA. Support or Funding Information U.S. DOE, Hispanic‐Serving Institutions, STEM Articulation Grant P031C110128 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

MacGregor, Michael Charles↗
DOE OSTI2019

Comparative efficacy of valnoctamide and sec ‐butylpropylacetamide ( SPD ) in terminating nerve agent–induced seizures in pediatric rats

Summary Objectives Children and adults are likely to be among the casualties in a civilian nerve agent exposure. This study evaluated the efficacy of valnoctamide (racemic‐VCD), sec ‐butylpropylacetamide (racemic‐SPD), and phenobarbital for stopping nerve agent seizures in both immature and adult rats. Methods Female and male postnatal day ( PND ) 21, 28, and 70 (adult) rats, previously implanted with electroencephalography (EEG) electrodes were exposed to seizure‐inducing doses of the nerve agents sarin or VX and EEG was recorded continuously. Five minutes after seizure onset, animals were treated with SPD , VCD, or phenobarbital. The up‐down method was used over successive animals to determine the anticonvulsant median effective dose (ED 50 ) of the drugs. Results SPD‐ED 50 values in the VX model were the following: PND 21, 53 mg/kg (male) and 48 mg/kg (female); PND 28, 108 mg/kg (male) and 43 mg/kg (female); and PND 70, 101 mg/kg (male) and 40 mg/kg (female). SPD ‐ ED 50 values in the sarin model were the following: PND 21, 44 mg/kg (male) and 28 mg/kg (female); PND 28, 79 mg/kg (male) and 34 mg/kg (female); and PND 70, 53 mg/kg (male) and 53 mg/kg (female). VCD ‐ ED 50 values in the VX model were the following: PND 21, 34 mg/kg (male) and 43 mg/kg (female); PND 28, 165 mg/kg (male) and 59 mg/kg (female); and PND 70, 87 mg/kg (male) and 91 mg/kg (female). VCD ‐ ED 50 values in the sarin model were the following: PND 21, 45 mg/kg (male), 48 mg/kg (female); PND 28, 152 mg/kg (male) 79 mg/kg (female); and PND 70, 97 mg/kg (male) 79 mg/kg (female). Phenobarbital‐ ED 50 values in the VX model were the following: PND 21, 43 mg/kg (male) and 18 mg/kg (female); PND 28, 48 mg/kg (male) and 97 mg/kg (female). Phenobarbital‐ ED 50 values in the sarin model were the following: PND 21, 32 mg/kg (male) and 32 mg/kg (female); PND 28, 58 mg/kg (male) and 97 mg/kg (female); and PND 70, 65 mg/kg (female). Significance SPD and VCD demonstrated anticonvulsant activity in both immature and adult rats in the sarin‐ and VX ‐induced status epilepticus models. Phenobarbital was effective in immature rats, whereas in adult rats, higher doses were required that were accompanied by toxicity. Overall, significantly less drug was required to stop seizures in PND 21 animals than in the older animals, and overall, males required higher amounts of drug than females.

Haines, Kari M.↗
DOE OSTI2015

SU-E-J-07: IGRT Gently: Evaluating Imaging Dose in Phantoms of Different Sizes

Purpose: IGRT imaging procedures have emerged as a common method of patient position verification in radiotherapy, though imaging dose is generally neglected in the treatment plan. Consequently, evaluating and optimizing the dose from these procedures is worthwhile. This process is especially important for children, who are more radiosensitive than adults. The aim of this work was to gain some understanding of the relative doses involved with various XVI-preset parameters for an “adult” and “child” phantom set, with the hopes that imaging dose for a child can be reduced. Methods: 32 and 16cm CTDI-phantoms were used as surrogates for adult and child torsos, respectively. Dose was measured in the central and peripheral chamber positions of the phantoms. CBCT scans were made for both phantoms using Elekta’s Chest-preset to establish a dose baseline. The child-phantom was then scanned using the Elekta Head and Neck (HN) preset. A modified HN-preset (named Peds Abd-pelvis) was also created with a doubled mAs to maintain a reduction in dose to the child-phantom (relative to the baseline), while providing clinically-usable image quality. Results: The baseline dose to the child-phantom from the Chest-preset was 310% that of the adult-phantom for the center chamber position and 150% at the periphery. An average dose reduction of 97% was obtained in the childphantom by switching from the Chest-preset to the HN-preset, while the Peds Abd-pelvis-preset similarly reduced the dose by an average of 92%. Conclusion: XVI-preset parameters significantly affect dose, and should be optimized to reduce dose, while ensuring clinically-usable image quality. Using a modified imaging preset (Peds Abd-pelvis-preset) greatly reduced the dose to the child-phantom compared to the dose for the Chest-preset for both the child and adult-phantoms. This outcome provides support for the development of child-specific protocols for IGRT imaging in pediatric patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Sexual Dimorphism in the Expression of Mitochondria-Related Genes in Rat Heart at Different Ages

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Moreover, sex and age are considered major risk factors in the development of CVDs. Mitochondria are vital for normal cardiac function, and regulation of mitochondrial structure and function may impact susceptibility to CVD. To identify potential role of mitochondria in sex-related differences in susceptibility to CVD, we analyzed the basal expression levels of mitochondriarelated genes in the hearts of male and female rats. Whole genome expression profiling was performed in the hearts of young (8-week), adult (21-week), and old (78-week) male and female Fischer 344 rats and the expression of 670 unique genes related to various mitochondrial functions was analyzed. A significant (p<0.05) sexual dimorphism in expression levels of 46, 114, and 41 genes was observed in young, adult and old rats, respectively. Gene Ontology analysis revealed the influence of sex on various biological pathways related to cardiac energy metabolism at different ages. The expression of genes involved in fatty acid metabolism was significantly different between the sexes in young and adult rat hearts. Adult male rats also showed higher expression of genes associated with the pyruvate dehydrogenase complex compared to females. In young and adult hearts, sexual dimorphism was not noted in genes encoding oxidative phosphorylation. In old rats, however, a majority of genes involved in oxidative phosphorylation had higher expression in females compared to males. Such basal differences between the sexes in cardiac expression of genes associated with energy metabolism may indicate a likely involvement of mitochondria in susceptibility to CVDs. In addition, female rats showed lower expression levels of apoptotic genes in hearts compared to males at all ages, which may have implications for better preservation of cardiac mass in females than in males.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility

Aging is accompanied by profound changes in the brain’s dopamine system that affect cognitive function. Evidence of powerful individual differences in cognitive aging has sharpened focus on identifying biological factors underlying relative preservation versus vulnerability to decline. Dopamine represents a key target in these efforts. Alterations of dopamine receptors and dopamine synthesis are seen in aging, with receptors generally showing reduction and synthesis demonstrating increases. Using the PET tracer 6-[ 18 F]fluoro-L- m -tyrosine, we found strong support for upregulated striatal dopamine synthesis capacity in healthy older adult humans free of amyloid pathology, relative to young people. We next used fMRI to define the functional impact of elevated synthesis capacity on cognitive flexibility, a core component of executive function. We found clear evidence in young adults that low levels of synthesis capacity were suboptimal, associated with diminished cognitive flexibility and altered frontoparietal activation relative to young adults with highest synthesis values. Critically, these relationships between dopamine, performance, and activation were transformed in older adults with higher synthesis capacity. Variability in synthesis capacity was related to intrinsic frontoparietal functional connectivity across groups, suggesting that striatal dopamine synthesis influences the tuning of networks underlying cognitive flexibility. Altogether, these findings define striatal dopamine’s association with cognitive flexibility and its neural underpinnings in young adults, and reveal the alteration in dopamine-related neural processes in aging.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Assessment of Potential Impact of Electromagnetic Fields from Undersea Cable on Migratory Fish Behavior

The US Department of Energy and US Department of the Interior, Bureau of Ocean Energy Management commissioned this study to address the limited scientific data on the impacts of high voltage direct current cables on aquatic biota, in particular migratory species within the San Francisco Bay. Empirical evidence exists that marine animals perceive and orient to local distortions in the earth’s main geomagnetic field magnetic field. The electromagnetic fields (EMF) generated by the cables that carry electricity from hydrokinetic energy sources to shore-based power stations may produce similar local distortions in the earth’s main field. Concern exists that animals that migrate along the continental shelves might orient to the EMF from the cables, and move either inshore or offshore away from their normal path. The Trans Bay Cable (TBC) is a ±200-kilovolt (kV), 400 MW 85-km long High Voltage Direct Current (DC) buried transmission line linking Pittsburg, CA with San Francisco, CA (SF) through the San Francisco Bay. The study addresses the following specific questions based on measurements and projections of the EMF produced by an existing marine cable, the TBC, in San Francisco Bay. Specifically, does the presence of EMF from an operating power cable alter the behavior and path of bony fishes and sharks along a migratory corridor? Does the EMF from an operating power cable guide migratory movements or pose an obstacle to movement? To meet the main study objectives several activities needed to be carried out: 1) modeling of the magnetic fields produced by the TBC, 2) assessing the migratory impacts on Chinook salmon smolts (Oncorhynchus tshawytscha) and green sturgeon (Acipenser medirostris) as a result of local magnetic field distortions produced by bridge structures and 3) analyzing behavioral responses by migratory Chinook salmon and green sturgeon to a high-voltage power cable. To meet the first objective, magnetic field measurements were made using two submerged Geometrics magnetometers towed behind a survey vessel in four locations in the San Francisco estuary along profiles crossing the cable path. We applied basic formulas to describe magnetic field from a DC cable summed vectorially with the background geomagnetic field (in the absence of other sources that would perturb the ambient field) to derive characteristics of the cable not immediately or otherwise observable. The magnetic field profiles of 76 survey lines were regressed against the measured fields, representing eight days of measurement. Many profiles were dominated by field distortions caused by bridge structures or other submerged objects, and the cable contribution to the field was not detectable. The regressions based on fundamental principles (Biot Savart law) and the vectorial summation of cable and geomagnetic fields provide estimates of cable characteristics consistent with plausible expectations. For the second objective, detailed gradiometer survey were examined. Distortions in the earth’s main field produced by bridges across the estuary were much greater than those from the TBC. The former anomalies exceeded the latter by an order of magnitude or more. Significant numbers of tagged Chinook salmon smolts migrated past bridges, which produced strong magnetic anomalies, to the Golden Gate Bridge, where they were recorded by dual arrays of acoustic tag-detecting monitors moored in lines across the mouth of the bay. Adult green sturgeon successfully swam upstream and downstream through the estuary on the way to and from their spawning grounds. Hence, the large anomalies produced by the bridges that run perpendicular to these migration routes do not appear to present a strong barrier to the natural seasonal movement patterns of salmonid smolts and adult green sturgeon. Finally, to assess the behavioral responses by migratory Chinook salmon and green sturgeon to a high- voltage power cable - the potential impacts effect of the TBC on fishes migrating through the San Francisco Estuary were examined. These included late-fall run Chinook salmon smolts (Oncorhynchus tshawytscha) that migrate downstream through the San Francisco Estuary to the Pacific Ocean and adult green sturgeon (Acipenser medirostris), which migrate upstream from the ocean through the estuary to their spawning habitat in the upper Sacramento River and return to the ocean after spawning occurs. Our results indicate Chinook salmon smolts may be attracted to the cable after activation (more cable location crossings, more detections at Bay Bridge, high importance of distance to cable in predicting fish location), but are not impeded from successfully migrating through the San Francisco Bay (similar proportions of successful exits, faster transit rates). Cable activity had opposite effects on outbound and inbound green sturgeon migrations: outbound migrations had significantly longer transit times while inbound migrations had significantly shorter migration times. However, the proportion of green sturgeon that successfully migrated through the San Francisco Bay was not strongly impacted after cable activation for either migration type. Based on the work, we provide the following conclusions: 1) calculations of magnetic fields for assessment of marine life can be performed; however, local anomalies in the fields resulting from submerged structures require validation of such calculations through collection of ambient DC magnetic field data, 2) the large anomalies produced by the bridges that run perpendicular to these migration routes do not appear to present a strong barrier to the natural seasonal movement patterns of salmonid smolts and adult green sturgeon and 3) Chinook salmon smolts may be attracted to the activated cable based on analysis of cable crossing, misdirections, and first presence at the array data, however, the cable activation does not appear to change the proportion of smolts that successfully migrate through the San Francisco Bay. Cable activation impacts inbound and outbound migrating adult green sturgeon: travel time was increased for outbound migrations but decreased for inbound migrations. However, cable activation did not appear to impact the success of either migration type in this species.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2015

CDC and YMCA: A Promising Partnership for Delivering Fall Prevention Programing

Falls threaten the independence of adults aged 65 years and older. In the U.S., one in three older adults fall annually, causing significant disability and reduced quality of life (1). The high prevalence of falls, coupled with more than $30 billion in direct medical costs (2) has created a critical need for effective older adult fall prevention programs. As the nation’s public health agency, the Centers for Disease Control and Prevention (CDC) is committed to identifying ways to reduce the burden of older adult falls. In this commentary, we describe a promising approach to reach older adults with effective interventions by partnering with the YMCA to deliver community-based fall prevention programs.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1990

Age effects on rat hindlimb muscle atrophy during suspension unloading

The effects of hindlimb unloading on muscle mass and biochemical responses were examined and compared in adult (450-g) and juvenile (200-g) rats after 1, 7, or 14 days of whole-body suspension. Quantitatively and qualitatively the soleus, gastrocnemius, plantaris, and extensor digitorum longus (EDL) muscles of the hindlimb exhibited a differential sensitivity to suspension and weightlessness unloading in both adults and juveniles. The red slow-twitch soleus exhibited the most pronounced atrophy under both conditions, with juvenile responses being greater than adult. In contrast, the fast-twitch EDL hypertrophied during suspension and atrophied during weightlessness, with no significant difference between adults and juveniles. Determination of biochemical parameters (total protein, RNA, and DNA) indicates a less rapid rate of response in adult muscles.

Steffen, Joseph M.↗
NASA NTRS1995

Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

Adams, Gregory R.↗
NASA NTRS1996

Insect Development in Altered Gravitational Environment

When tobacco hornworm (Manduca sexta) larvae burrow underground (25-30 cm) to pupate, they reorient themselves to a relatively horizontal position indicating an ability to sense gravity. To evaluate their sensitivity to gravitational environment during metamorphosis, Manduca (pharate adults) were placed in a vertical (head-up) position. Distinct morphological changes, each one reflecting ensuing phases, were used to follow adult development. Five days after pupation, the vertical group showed accelerated (P less than 0.05) development and were nearly 4 phases ahead (P less than 0.0001) after 10 days. Differences in development in the vertical group were characterized further by increased (7-48%) hemolymph concentrations of 13 amino acids, but a decrease in cys and pro and no change in arg, his, met and val (trp, undetectable). Decreased (36%) turnover of injected H-3 - phenylalanine suggested slower utilization of amino acids contributed, at least partly, to the increased concentrations. Vertically-oriented Manduca also exhibited a greater (20 %, P less than 0.001) protein content in their flight muscles near the end of development. Analysis of hemolymph sugar levels showed a redistribution of sugars from the monosaccharide glucose to the disaccharide trehalose. Since injection of 20-hydroxyecdysone decreased (49%) turnover of H-3- phenylalanine in pharate adults and since ecdysteroids are known to increase flight muscle size and control adult development, these results are consistent with our measuring a greater (+80%, P less than 0.05) ecdysteroid titer in the vertically-oriented insects. These results suggest that gravity environment influences ecdysone output by the pharate adult. When we evaluated hemolymph flow in the head-up and control positions, we found that injected C-14-inulin was distributed somewhat more rapidly in the head-up group irrespective of the sight of injection (head or abdomen) likely because in the head-up position flow of the hemolymph is facilitated throughout the animal. Other experiments showed that an intact prothoracic gland is needed for the response. Hence vertical, head-up orientation affects release of ecdysone from the prothoracic gland.

Tischler, Marc E.↗
NASA NTRS1996

Effect of Altered Gravity Environment on Tobacco Hornworm (Manduca Sexta) Development

Metamorphosis provides a unique condition for studying the role of gravity in development. Formation of new organs in a previously existing organism requires a highly active period of turnover of amino acids and proteins, and of changes in the endocrine profile. Furthermore, metamorphosis offers the advantage of studying a self-contained biological system. The tobacco hornworm provides a suitable species to study the effect of altered gravitational environment on invertebrate development. This species has been one of the most thoroughly investigated organisms in a variety of aspects of insect biology. M. sexta pharate adults can provide significant amounts of material with which to work, thus facilitating the study of metabolic aspects of adult development. During wandering, the period immediately following cessation of larval feeding, the larva burrows into the soil to form a pupation chamber. Despite burrowing down 25 to 30 cm, the insects reorient themselves to a slightly head-up (10 +/- 1 degree) position. Since light and temperature are not factors in this process, the larvae must sense the gravity vector. In our ground-based studies we had assessed whether developing adults might be sensitive to their gravitational environment by orienting pupae in a vertical head-up position within 24 to 48 h after pupal ecdysis. Our ground-based findings formed the foundation for determining which parameters would be evaluated in developing Manduca following spaceflight. Measurements were to include: (1) extent of development by all of the insects, (2) analysis of hemolymph obtained from half of the insects postflight for ecdysteroid, amino acid, urea, ammonia and trehalose concentrations, (3) further development of the other half of the insects to adult (moths), (4) analysis of the flight muscle protein content of the adults. Based on the first flight attempt in July, 1995, we modified the BRIC hardware to accommodate the insects. Our studies after BRIC-04 showed that sealing the top and bottom lids of the canisters with an 0-ring and with vacuum grease caused the insects to stop developing because of accumulation of carbon dioxide. Even though removing both the O-rings and vacuum grease permitted normal development, there was still some increase in carbon dioxide levels. Consequently, the canisters were vented and the vents covered with gas permeable membrane.

Tischler, Marc E.↗
NASA NTRS1999

Laser ablation of persistent twist cells in Drosophila: muscle precursor fate is not segmentally restricted

In Drosophila the precursors of the adult musculature arise during embryogenesis. These precursor cells have been termed Persistent Twist Cells (PTCs), as they continue to express the transcription factor Twist after that gene ceases expression elsewhere in the mesoderm. In the larval abdomen, the PTCs are associated with peripheral nerves in stereotypic ventral, dorsal, and lateral clusters, which give rise, respectively, to the ventral, dorsal, and lateral muscle fiber groups of the adult. We tested the developmental potential of the PTCs by using a microbeam laser to ablate specific clusters in larvae. We found that the ablation of a single segmental PTC cluster does not usually result in the deletion of the corresponding adult fibers of that segment. Instead, normal or near normal numbers of adult fibers can form after the ablation. Examination of pupae following ablation showed that migrating PTCs from adjacent segments are able to invade the affected segment, replenishing the ablated cells. However, the ablation of homologous PTCs in multiple segments does result in the deletion of the corresponding adult muscle fibers. These data indicate that the PTCs in an abdominal segment can contribute to the formation of muscle fibers in adjacent abdominal segments, and thus are not inherently restricted to the formation of muscle fibers within their segment of origin.

NASA Discipline Neuroscience↗
NASA NTRS2005

Prenatal Centrifugation: A Mode1 for Fetal Programming of Body Weight?

'Fetal programming' is a newly emerging field that is revealing astounding insights into the prenatal origins of adult disease, including metabolic, endocrine, and cardiovascular pathophysiology. In the present study, we tested the hypothesis that rat pups conceived, gestated and born at 2-g have significantly reduced birth weights and increased adult body weights as compared to 1-g controls. Offspring were produced by mating young adult male and female rats that were adapted to 2-g centrifugation. Female rats underwent conception, pregnancy and birth at 2-g. Newborn pups in the 2-g condition were removed from the centrifuge and fostered to non-manipulated, newly parturient dams maintained at 1 -g. Comparisons were made with 1-g stationary controls, also crossfostered at birth. As compared to 1-g controls, birth weights of pups gestated and born at 2-g were significantly reduced. Pup body weights were significantly reduced until Postnatal day (P) 12. Beginning on P63, body weights of 2-g-gestated offspring exceeded those of 1-g controls by 7-10%. Thus, prenatal rearing at 2-g restricts neonatal growth and increases adult body weight. Collectively, these data support the hypothesis that 2-g centrifugation alters the intrauterine milieu, thereby inducing persistent changes in adult phenotype.

Baer, Lisa A.↗
DOE OSTI2016

Neuroplastic Response After Radiation Therapy for Pediatric Brain Tumors: A Pilot Study

Purpose: Clinically effective measurement of cognitive toxicity from photon radiation therapy (XRT) should be accurate, sensitive, and specific. This pilot study tested translational findings on phasic changes in children's memory systems that are sensitive and insensitive to toxic XRT effects to identify a possible neuroplastic effect. Methods and Materials: Memory processes were prospectively tested before XRT and at 3 later time points up to 2 years in 35 children with mixed primary brain tumors who had not experienced recurrence. Memory processes were verbal-semantic, visual-semantic, and visual-perceptual, including accuracy, speed to recall, encoding, retrieval, and recognition. The mixed-effects model included time (to estimate slope), covariates (age, tumor locus, XRT field, and medications) as fixed effects, and individual random intercepts. A sensitivity analysis examined the influence of XRT dose to the hippocampi on memory. Results: Retrieval from long-term verbal-semantic memory declined 2 months after completing XRT, as seen in adults, and was lowest at 1 year, which was delayed in comparison with adults. Double dissociation from visual-perceptual memory at baseline and 2 months was found, consistent with adults. Recovery was demonstrated 2 years after XRT. Patterns were unchanged when dose to hippocampus was included in the model. Conclusions: Verbal and semantic long-term retrieval is specifically sensitive to XRT-related cognitive dysfunction, without effect on visual-perceptual memory. Children reached nadir in XRT-sensitive memory 1 year after XRT and recovered by 2 years, which is later than that observed in adults. The protracted period of post-XRT injury may represent the maturation of the human hippocampus and white matter into late adolescence.

62 RADIOLOGY AND NUCLEAR MEDICINE↗