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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 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
NASA NTRS1987

Control of abdominal and expiratory intercostal muscle activity during vomiting - Role of ventral respiratory group expiratory neurons

The role of ventral respiratory group (VRG) expiratory (E) neurons in the control of abdominal and internal intercostal muscle activity during vomiting was investigated in cats. Two series of experiments were performed: in one, the activity of VRG E neurons was recorded during fictive vomiting in cats that were decerebrated, paralyzed, and artificially ventilated; in the second, the abdominal muscle activity during vomiting was compared before and after sectioning the axons of descending VRG E neurons in decerebrate spontaneously breathing cats. The results show that about two-thirds of VRG E neurons that project at least as far caudally as the lower thoracic cord contribute to internal intercostal muscle activity during vomiting. The remaining VRG E neurons contribute to abdominal muscle activation. As shown by severing the axons of the VRG E neurons, other, as yet unidenified, inputs (either descending from the brain stem or arising from spinal reflexes) can also produce abdominal muscle activation.

Miller, Alan D.↗
NASA NTRS1988

Immunocytochemical localization of glutamic acid decarboxylase (GAD) and substance P in neural areas mediating motion-induced emesis: Effects of vagal stimulation on GAD immunoreactivity

Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid (GABA) by means of its biosynthetic enzyme glutamic acid decarboxylase (GAD) and the neuropeptide substance P in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), and gelatinous nucleus (GEL). In addition, electrical stimulation was applied to the night vagus nerve at the cervical level to assess the effects on GAD-immunoreactivity (GAR-IR). GAD-IR terminals and fibers were observed in the AP, ASP, NTS, and GEL. They showed pronounced density at the level of the ASP and gradual decrease towards the solitary complex. Nerve cells were not labelled in our preparations. Ultrastructural studies showed symmetric or asymmetric synaptic contracts between labelled terminals and non-immunoreactive dendrites, axons, or neurons. Some of the labelled terminals contained both clear- and dense-core vesicles. Our preliminary findings, after electrical stimulation of the vagus nerve, revealed a bilateral decrease of GAD-IR that was particularly evident at the level of the ASP. SP-immunoreactive (SP-IR) terminals and fibers showed varying densities in the AP, ASP, NTS, and GEL. In our preparations, the lateral sub-division of the NTS showed the greatest accumulation. The ASP showed medium density of immunoreactive varicosities and terminals and the AP and GEL displayed scattered varicose axon terminals. The electron microscopy revealed that all immunoreactive terminals contained clear-core vesicles which make symmetric or asymmetric synaptic contact with unlabelled dendrites. It is suggested that the GABAergic terminals might correspond to vagal afferent projections and that GAD/GABA and substance P might be co-localized in the same terminal allowing the possibility of a regulated release of the transmitters in relation to demands.

GABA↗
NASA NTRS1995

Chemical Topography of Efferent Projections from the Median Preoptic Nucleus to Pontine Monoaminergic Cell Groups in the Rat

This study examined efferent output from the median preoptic nucleus (MNPO) to pontine noradrenergic and serotonergic cell groups using an anterograde tracing technique (Phaseolus vulgaris leucoagglutinin, PHA-L) combined with glucose oxidase immunocytochemistry to serotonin (5-HT) or to dopamine-beta-hydroxylase (DBH). Injections of PHA-L into the ventral MNPO resulted in moderate axonal labeling within the region of the B7 and B8 serotonergic groups in the dorsal raphe. PHA-L labeled fibers and punctate processes were observed in close apposition to many of the 5-HT immunoreactive neurons in these regions. In contrast, sparse terminal labeling was found within the B5 group in the raphe pontis nucleus, and only trace fiber labeling observed in the B3 and B6 groups. Efferents from the MNPO also provided moderate innervation to the A6 and A7 noradrenergic groups. PHA-L labeled punctate processes were found most frequently in close apposition to DBH-immunoreactive neurons at mid- to caudal levels of the locus coeruleus. Some labeled axons were also present within the A7 and A5 groups. Additionally, a close apposition between labeled MNPO efferents and 5-HT fibers within the lateral parabrachial nucleus was observed. The results indicate the MNPO provides a topographic innervation of monoaminergic groups in the upper brainstem.

Zardetto-Smith, Andrea M.↗
NASA NTRS1995

Chemical Topography of Efferent Projections from the Median Preoptic Nucleus to Pontine Monoaminergic Cell Groups in the Rat

This study examined efferent output from the median preoptic nucleus (MnPO) to pontine noradrenergic and serotonergic cell groups using an anterograde tracing technique (Phaseolus vulgaris leucoagglutinin, PHA-L) combined with glucose oxidase immunocytochemistry to scrotonin (5-HT) or to dopamine-(beta)-hydroxylase (DBH). Injections of PHA-L into the ventral MNPO resulted in moderate axonal labeling within the region of the B7 and B8 serotonergic groups in the dorsal raphe. PHA-L labeled fibers and punctate processes were observed in close apposition to many of the 5-HT immunoreactive neurons in these regions, In contrast, sparse terminal labeling was found within the B5 group in the raphe pontis nucleus, and only trace fiber labeling observed in the B3 and B6 groups. Efferents from the MNPO also provided moderate innervation to the A6 and A7 noradrenergic groups. PHA-L labeled punctate processes were found most frequently in close apposition to DBH-immunorcactive neurons at mid- to caudal levels of the locus coeruleus. Some labeled axons were also present within the A7 and A5 groups. Additionally, a close apposition between labeled MNPO efferents and 5-HT fibers within the lateral parabrachial nucleus was observed, The results indicate the MNPO provides a topographic innerva- tion of monoaminergic groups in the upper brainstem.

Zardetto-Smith, Andrea M.↗
NASA NTRS1998

Effects of Weightlessness on Vestibular Development: Summary of Research on NIH.R1

In our original application we proposed to investigate the effects of gravity on the formation of connections between the gravity receptors of the ear and the brain in rat pups raised in space beginning at an age before these connections are made until near the time of birth, when they are to some extent functional. We used the neuronal tracer, Dil, which could be applied to tissue obtained immediately after landing of the space shuttle, thus minimizing changes due to the earth's gravity. We hoped to determine whether the vestibular system develops in two phases, as do other sensory systems (such as the visual system). In these other systems the first phase of development is controlled genetically and the second phase is controlled by environmental stimulation. Our data collected strongly supports the idea that the vestibular system has these same two phases of development. The tissue obtained from the NIH.R1 experiment was of exceptionally high quality for our analysis. Therefore, we expanded our investigation into the ultrastructural effects of microgravity on vestibular development. For the sake of clarity we will subdivide our summary into two categories: (1) analysis of the branching pattern of axons between the vestibular nerve and the gravistatic receptors of the ear in flight and control animals, and (2) analysis of the branching pattern of axons between the vestibular nerve and the brain in flight and control animals.

Fritzsch, Bernd↗
NASA NTRS1997

The Structure of the Statocyst of the Freshwater Snail Biomphalaria Glabrata (Pulmonata, Basommatophora)

The structure of the statocyst of the freshwater snail Biomphalaria glabrata has been examined by light and electron microscopy. The two statocysts are located on the dorsal-lateral side of the left and right pedal ganglion. The statocysts are spherical, fluid-filled capsules with a diameter of approximately 60 microns for young and 110 microns for adult snails. The wall of the cyst is composed of large receptor cells and many smaller supporting cells. The receptor cells bear cilia which are evenly distributed on the apical surface. The cilia have the typical 9+2 internal tubule configuration. Striate rootlets originate from the base of the basal body and run downward into the cytoplasm. Side-roots arise from one side of the basal body and a basal foot from the other. For each receptor cell, the basal foot always points to the periphery of the surface, indicating that the receptor cell is non-polarized. The receptor cells contain cytoplasmic organelles such as mitochondria, ribosomes, rough and smooth endoplasmic reticulum, compact Golgi bodies and multivesicular bodies. Supporting cells bearing microvilli are interposed between the receptor cells. The junction complex between the supporting cells and the receptor cells is composed of adherens and septate junctions, while between supporting cells only the adherens junctions are present. The static nerve arises from the lateral side of the cyst and contains axons in which parallel neurotubules and mitochondria are found. The axons arise directly from the base of the receptor cells without synapse. In the cyst lumen there are unattached statoconia. The statoconia have a plate-like or concentric membranous ring structure. Based on the morphology, the function of the statocyst in Biomphalaria is discussed.

Gao, Wenyuan↗
NASA NTRS2001

Evolution of neural crest and placodes: amphioxus as a model for the ancestral vertebrate?

Recent studies of protochordates (ascidian tunicates and amphioxus) have given insights into possible ancestors of 2 of the characteristic features of the vertebrate head: neural crest and placodes. The neural crest probably evolved from cells on either side of the neural plate-epidermis boundary in a protochordate ancestral to the vertebrates. In amphioxus, homologues of several vertebrate neural crest marker genes (BMP2/4, Pax3/7, Msx, Dll and Snail) are expressed at the edges of the neural plate and/or adjacent nonneural ectoderm. Some of these markers are also similarly expressed in tunicates. In protochordates, however, these cells, unlike vertebrate neural crest, neither migrate as individuals through embryonic tissues nor differentiate into a wide spectrum of cell types. Therefore, while the protochordate ancestor of the vertebrates probably had the beginnings of a genetic programme for neural crest formation, this programme was augmented in the earliest vertebrates to attain definitive neural crest. Clear homologues of vertebrate placodes are lacking in protochordates. However, both amphioxus and tunicates have ectodermal sensory cells. In tunicates these are all primary neurons, sending axons to the central nervous system, while in amphioxus, the ectodermal sensory cells include both primary neurons and secondary neurons lacking axons. Comparisons of developmental gene expression suggest that the anterior ectoderm in amphioxus may be homologous to the vertebrate olfactory placode, the only vertebrate placode with primary, not secondary, neurons. Similarly, biochemical, morphological and gene expression data suggest that amphioxus and tunicates also have homologues of the adenohypophysis, one of the few vertebrate structures derived from nonneurogenic placodes. In contrast, the origin of the other vertebrate placodes is very uncertain.

NASA Discipline Evolutionary Biology↗
NASA NTRS2000

GLUT-3 expression in human skeletal muscle

Muscle biopsy homogenates contain GLUT-3 mRNA and protein. Before these studies, it was unclear where GLUT-3 was located in muscle tissue. In situ hybridization using a midmolecule probe demonstrated GLUT-3 within all muscle fibers. Fluorescent-tagged antibody reacting with affinity-purified antibody directed at the carboxy-terminus demonstrated GLUT-3 protein in all fibers. Slow-twitch muscle fibers, identified by NADH-tetrazolium reductase staining, possessed more GLUT-3 protein than fast-twitch fibers. Electron microscopy using affinity-purified primary antibody and gold particle-tagged second antibody showed that the majority of GLUT-3 was in association with triads and transverse tubules inside the fiber. Strong GLUT-3 signals were seen in association with the few nerves that traversed muscle sections. Electron microscopic evaluation of human peripheral nerve demonstrated GLUT-3 within the axon, with many of the particles related to mitochondria. GLUT-3 protein was found in myelin but not in Schwann cells. GLUT-1 protein was not present in nerve cells, axons, myelin, or Schwann cells but was seen at the surface of the peripheral nerve in the perineurium. These studies demonstrated that GLUT-3 mRNA and protein are expressed throughout normal human skeletal muscle, but the protein is predominantly found in the triads of slow-twitch muscle fibers.

NASA Discipline Regulatory Physiology↗
NASA NTRS1998

Clinical and electrophysiologic attributes as predictors of results of autonomic function tests

Autonomic dysfunction is a feature of some neuropathies and not others. It has been suggested that some clinical and electrophysiologic attributes are predictable of autonomic impairment detected using laboratory testing; however, dear guidelines are unavailable. We evaluated 138 relatively unselected patients with peripheral neuropathy who underwent neurologic evaluation, electromyography (EMG), nerve conduction studies, and autonomic function tests to determine which variables were predictive of laboratory findings of autonomic failure. The variables evaluated were 1) clinical somatic neuropathic findings, 2) clinical autonomic symptoms, and 3) electrophysiologic findings. Autonomic symptoms were strongly predictive (Rs = 0.40, p < 0.001) of autonomic failure. Among the non-autonomic indices, absent ankle reflexes were mildly predictive (Rs = 0.19, p = 0.022) of autonomic impairment, but all others were not (duration, clinical pattern, severity, weakness, sensory loss). Electrophysiologic changes of an axonal neuropathy predicted autonomic impairment while demyelinating neuropathy did not. We conclude that autonomic studies will most likely be abnormal in patients who have symptoms of autonomic involvement and those who have an axonal neuropathy.

Controlled Clinical Trial↗
NASA NTRS2014

Protecting Neural Structures and Cognitive Function During Prolonged Space Flight by Targeting the Brain Derived Neurotrophic Factor Molecular Network

Brain derived neurotrophic factor (BDNF) is the main activity-dependent neurotrophin in the human nervous system. BDNF is implicated in production of new neurons from dentate gyrus stem cells (hippocampal neurogenesis), synapse formation, sprouting of new axons, growth of new axons, sprouting of new dendrites, and neuron survival. Alterations in the amount or activity of BDNF can produce significant detrimental changes to cortical function and synaptic transmission in the human brain. This can result in glial and neuronal dysfunction, which may contribute to a range of clinical conditions, spanning a number of learning, behavioral, and neurological disorders. There is an extensive body of work surrounding the BDNF molecular network, including BDNF gene polymorphisms, methylated BDNF gene promoters, multiple gene transcripts, varied BDNF functional proteins, and different BDNF receptors (whose activation differentially drive the neuron to neurogenesis or apoptosis). BDNF is also closely linked to mitochondrial biogenesis through PGC-1alpha, which can influence brain and muscle metabolic efficiency. BDNF AS A HUMAN SPACE FLIGHT COUNTERMEASURE TARGET Earth-based studies reveal that BDNF is negatively impacted by many of the conditions encountered in the space environment, including oxidative stress, radiation, psychological stressors, sleep deprivation, and many others. A growing body of work suggests that the BDNF network is responsive to a range of diet, nutrition, exercise, drug, and other types of influences. This section explores the BDNF network in the context of 1) protecting the brain and nervous system in the space environment, 2) optimizing neurobehavioral performance in space, and 3) reducing the residual effects of space flight on the nervous system on return to Earth

Schmidt, M. A.↗
DOE OSTI2024

The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma

A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells. We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results. We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown. Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Lipids status and copper in a single astrocyte of the rat model for amyotrophic lateral sclerosis: Correlative synchrotron-based X-ray and infrared imaging

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, causing death of motor neurons controlling voluntary muscles. The pathological mechanisms of the disease are only partially understood. The hSOD1-G93A ALS rat model is characterized by an overexpression of human mutated SOD1, causing increased vulnerability by forming intracellular protein aggregates, inducing excitotoxicity, affecting oxidative balance and disturbing axonal transport. In this study we followed the bio-macromolecular organic composition and compartmentalization together with trace metal distribution in situ in single astrocytes from the ALS rat model and compared them to the control astrocytes from nontransgenic littermates by simultaneous use of two synchrotron radiation-based methods: Fourier transform infrared microspectroscopy (SRFTIR) and hard X-ray fluorescence microscopy (XRF). Here we show that ALS cells contained more Cu, which colocalized with total lipids, increased carbonyl groups and oxidized lipids, thus implying direct involvement of Cu in oxidative stress of lipidic components without direct connection to protein aggregation in situ.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

BrainXcan identifies brain features associated with behavioral and psychiatric traits using large-scale genetic and imaging data

Advances in brain MRI have enabled many discoveries in neuroscience. Case-control comparisons of brain MRI features have highlighted potential causes of psychiatric and behavioral disorders. However, due to the cost and difficulty of collecting MRI data, most studies have small sample sizes, limiting their reliability. Furthermore, reverse causality complicates interpretation because many observed brain differences are the result rather than the cause of the disease. Here we propose a method (BrainXcan) that leverages the power of large-scale genomewide association studies (GWAS) and reference brain MRI data to discover new mechanisms of disease etiology and validate existing ones. BrainXcan tests the association with genetic predictors of brain MRI-derived features and complex traits to pinpoint relevant brain-wide and region-specific features. Requiring only genetic data, BrainXcan allows us to test a host of hypotheses on mental illness, across many MRI modalities, using public data resources. For example, our method shows that reduced axonal density across the brain is associated with schizophrenia risk, consistent with the disconnectivity hypothesis. We also find that the hippocampus volume is associated with schizophrenia risk, highlighting the potential of our approach. Taken together, our results show the promise of BrainXcan to provide insights into the biology of GWAS traits.

Association study↗
DOE OSTI2021

Dl-3-n-butylphthalide promotes neurite outgrowth of primary cortical neurons by Sonic Hedgehog signaling via upregulating Gap43

Highlights: • NBP promoted neurite outgrowth in immature primary cortical neurons. • NBP increased axon and dendrite extension in mature primary cortical neurons. • NBP promoted neuritogenesis and neuronal plasticity via Shh signaling pathway. • The Shh signaling pathway increased Gap43 expression in primary cortical neuron. • NBP promoted neurite outgrowth by Shh signaling via upregulating Gap43 expression. Neurite outgrowth is the basis for wiring during the development of the nervous system. Dl-3-n-butylphthalide (NBP) has been recognized as a promising treatment to improve behavioral, neurological and cognitive outcomes in ischemic stroke. However, little is known about the effect and mechanism of NBP on the neurite outgrowth. In this study, we used different methods to investigate the potential effects of NBP on the neurite extension and plasticity of immature and mature primary cortical neurons and explored the underlying mechanisms. Our results demonstrated that in immature and mature cortical neurons, NBP promoted the neurite length and intersections, increased neuritic arborization, elevated numbers of neurite branch and terminal points and improved neurite complexity and plasticity of neuronal development processes. Besides, our data revealed that NBP promoted neurite extension and branching partly by activating Shh signaling pathway via increasing Gap43 expression both in immature and mature primary cortical neurons. The present study provided new insights into the contribution of NBP in neuronal plasticity and unveiled a novel pathway to induce Gap43 expression in primary cortical neurons.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Determinants of synapse diversity revealed by super-resolution quantal transmission and active zone imaging

Neural circuit function depends on the pattern of synaptic connections between neurons and the strength of those connections. Synaptic strength is determined by both postsynaptic sensitivity to neurotransmitter and the presynaptic probability of action potential evoked transmitter release (P r ). Whereas morphology and neurotransmitter receptor number indicate postsynaptic sensitivity, presynaptic indicators and the mechanism that sets P r remain to be defined. To address this, we developed QuaSOR, a super-resolution method for determining P r from quantal synaptic transmission imaging at hundreds of glutamatergic synapses at a time. We mapped the P r onto super-resolution 3D molecular reconstructions of the presynaptic active zones (AZs) of the same synapses at the Drosophila larval neuromuscular junction (NMJ). We find that P r varies greatly between synapses made by a single axon, quantify the contribution of key AZ proteins to P r diversity and find that one of these, Complexin, suppresses spontaneous and evoked transmission differentially, thereby generating a spatial and quantitative mismatch between release modes. Transmission is thus regulated by the balance and nanoscale distribution of release-enhancing and suppressing presynaptic proteins to generate high signal-to-noise evoked transmission.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Dense, continuous membrane labeling and expansion microscopy visualization of ultrastructure in tissues

Abstract Lipid membranes are key to the nanoscale compartmentalization of biological systems, but fluorescent visualization of them in intact tissues, with nanoscale precision, is challenging to do with high labeling density. Here, we report ultrastructural membrane expansion microscopy (umExM), which combines an innovative membrane label and optimized expansion microscopy protocol, to support dense labeling of membranes in tissues for nanoscale visualization. We validate the high signal-to-background ratio, and uniformity and continuity, of umExM membrane labeling in brain slices, which supports the imaging of membranes and proteins at a resolution of ~60 nm on a confocal microscope. We demonstrate the utility of umExM for the segmentation and tracing of neuronal processes, such as axons, in mouse brain tissue. Combining umExM with optical fluctuation imaging, or iterating the expansion process, yields ~35 nm resolution imaging, pointing towards the potential for electron microscopy resolution visualization of brain membranes on ordinary light microscopes.

Science & Technology - Other Topics↗
DOE OSTI2020

An interphase pool of KIF11 localizes at the basal bodies of primary cilia and a reduction in KIF11 expression alters cilia dynamics

KIF11 is a homotetrameric kinesin that peaks in protein expression during mitosis. It is a known mitotic regulator, and it is well-described that KIF11 is necessary for the formation and maintenance of the bipolar spindle. However, there has been a growing appreciation for non-mitotic roles for KIF11. KIF11 has been shown to function in such processes as axon growth and microtubule polymerization. We previously demonstrated that there is an interphase pool of KIF11 present in glioblastoma cancer stem cells that drives tumor cell invasion. Here, we identified a previously unknown association between KIF11 and primary cilia. We confirmed that KIF11 localized to the basal bodies of primary cilia in multiple cell types, including neoplastic and non-neoplastic cells. Further, we determined that KIF11 has a role in regulating cilia dynamics. Upon the reduction of KIF11 expression, the number of ciliated cells in asynchronously growing populations was significantly increased. We rescued this effect by the addition of exogenous KIF11. Lastly, we found that depleting KIF11 resulted in an increase in cilium length and an attenuation in the kinetics of cilia disassembly. These findings establish a previously unknown link between KIF11 and the dynamics of primary cilia and further support non-mitotic functions for this kinesin.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Cdk5 mediates rotational force-induced brain injury

Abstract Millions of traumatic brain injuries (TBIs) occur annually. TBIs commonly result from falls, traffic accidents, and sports-related injuries, all of which involve rotational acceleration/deceleration of the brain. During these injuries, the brain endures a multitude of primary insults including compression of brain tissue, damaged vasculature, and diffuse axonal injury. All of these deleterious effects can contribute to secondary brain ischemia, cellular death, and neuroinflammation that progress for weeks, months, and lifetime after injury. While the linear effects of head trauma have been extensively modeled, less is known about how rotational injuries mediate neuronal damage following injury. Here, we developed a new model of repetitive rotational head trauma in rodents and demonstrated acute and prolonged pathological, behavioral, and electrophysiological effects of rotational TBI (rTBI). We identify aberrant Cyclin-dependent kinase 5 (Cdk5) activity as a principal mediator of rTBI. We utilized Cdk5-enriched phosphoproteomics to uncover potential downstream mediators of rTBI and show pharmacological inhibition of Cdk5 reduces the cognitive and pathological consequences of injury. These studies contribute meaningfully to our understanding of the mechanisms of rTBI and how they may be effectively treated.

60 APPLIED LIFE SCIENCES↗