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Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate the impact of spaceflight on the mouse brain in female mice. Our comparative analysis between ground control and spaceflight-exposed animals revealed significant alterations in essential brain processes including neurogenesis, synaptogenesis and synaptic transmission, particularly affecting the cortex, hippocampus, striatum and neuroendocrine structures. Additionally, we observed astrocyte activation and signs of immune dysfunction. At the pathway level, some spaceflight-induced changes in the brain exhibit similarities with neurodegenerative disorders, marked by oxidative stress and protein misfolding. Our integrated spatial multiomics approach serves as a stepping stone towards understanding spaceflight-induced CNS impairments at the level of individual brain regions and cell types, and provides a basis for comparison in future spaceflight studies. For broader scientific impact, all datasets from this study are available through an interactive data portal, as well as the National Aeronautics and Space Administration (NASA) Open Science Data Repository (OSDR). A spatial transcriptomics and single-cell multiomics study performed on mouse brain tissue. Here, authors show region-specific spaceflight-induced alterations in processes of neurogenesis, synaptogenesis and synaptic transmission.

Cosmic radiation experienced during space travel may increase the risk of cognitive impairment. While simulated galactic cosmic radiation (GCRsim) has led to memory deficits in wildtype (WT) mice, it has not been investigated whether GCRsim in combination with genetic risk factors for Alzheimer’s disease (AD) worsens memory further in aging mice. Here, we investigated the central nervous system (CNS) effects of 0 Gy (sham) or 0.75 Gy five-ion GCRsim or 2 Gy gamma radiation (IRR) in 14-month-old female and male APPNL-F/NL-F knock-in (KI) mice bearing humanized ApoE3 or ApoE4 (APP;E3F and APP;E4F). As travel to a specialized facility was required for irradiation, both traveled sham-irradiated C57BL/6J WT and KI mice and non-traveled (NT) KI mice acted as controls for potential effects of travel. Mice underwent four behavioral tests at 20 months of age and were euthanized for pathological and biochemical analyses 1 month later. Fecal samples were collected pre- and post-irradiation at four different time points. GCRsim seemed to impair memory in male APP;E3F mice compared to their sham counterparts. Travel tended to improve cognition in male APP;E3F mice and lowered total Aβ in female and male APP;E3F mice compared to their non-traveled counterparts. Sham-irradiated male APP;E4F mice accumulated more fibrillar amyloid than their APP;E3F counterparts. Radiation exposure had only modest effects on behavior and brain changes, but travel-, sex-, and genotype-specific effects were seen. Irradiated mice had immediate and long-term differences in their gut bacterial composition that correlated to Alzheimer’s disease phenotypes.

Space travel will expose people to high-energy, heavy particle radiation, and the cognitive deficits induced by this exposure are not well understood. To investigate the short-term effects of space radiation, we irradiated 4-month-old Alzheimer’s disease (AD)-like transgenic (Tg) mice and wildtype (WT) littermates with a single, whole-body dose of 10 or 50 cGy 56 Fe ions (1 GeV/u) at Brookhaven National Laboratory. At ~1.5 months post irradiation, behavioural testing showed sex-, genotype-, and dose-dependent changes in locomotor activity, contextual fear conditioning, grip strength, and motor learning, mainly in Tg but not WT mice. There was little change in general health, depression, or anxiety. Two months post irradiation, microPET imaging of the stable binding of a translocator protein ligand suggested no radiation-specific change in neuroinflammation, although initial uptake was reduced in female mice independently of cerebral blood flow. Biochemical and immunohistochemical analyses revealed that radiation reduced cerebral amyloid-β levels and microglia activation in female Tg mice, modestly increased microhemorrhages in 50 cGy irradiated male WT mice, and did not affect synaptic marker levels compared to sham controls. Taken together, we show specific short-term changes in neuropathology and behaviour induced by 56 Fe irradiation, possibly having implications for long-term space travel.

The Cosmology Large Angular Scale Surveyor (CLASS) will measure the polarization of the Cosmic Microwave Background to search for and characterize the polarized signature of inflation. CLASS will operate from the Atacama Desert and observe ∼ 70 % of the sky. A variable-delay polarization modulator provides modulation of the polarization at ∼ 10 Hz to suppress the 1/ f noise of the atmosphere and enable the measurement of the large angular scale polarization modes. The measurement of the inflationary signal across angular scales that spans both the recombination and reionization features allows a test of the predicted shape of the polarized angular power spectra in addition to a measurement of the energy scale of inflation. CLASS is an array of telescopes covering frequencies of 38, 93, 148, and 217 GHz. These frequencies straddle the foreground minimum and thus allow the extraction of foregrounds from the primordial signal. Each focal plane contains feedhorn-coupled transition-edge sensors that simultaneously detect two orthogonal linear polarizations. The use of single-crystal silicon as the dielectric for the on-chip transmission lines enables both high efficiency and uniformity in fabrication. Integrated band definition has been implemented that both controls the bandpass of the single-mode transmission on the chip and prevents stray light from coupling to the detectors.

Whole-body exposure to high-energy particle radiation remains an unmitigated hazard to human health in space. Ongoing experiments at the NASA Space Radiation Laboratory and elsewhere repeatedly show persistent changes in brain function long after exposure to simulations of this unique radiation environment, although, as is also the case with proton radiotherapy sequelae, how this occurs and especially how it interacts with common comorbidities is not well-understood. Here, we report modest differential changes in behavior and brain pathology between male and female Alzheimer’s-like and wildtype littermate mice 7–8 months after exposure to 0, 0.5, or 2 Gy of 1 GeV proton radiation. The mice were examined with a battery of behavior tests and assayed for amyloid beta pathology, synaptic markers, microbleeds, microglial reactivity, and plasma cytokines. In general, the Alzheimer’s model mice were more prone than their wildtype littermates to radiation-induced behavior changes, and hippocampal staining for amyloid beta pathology and microglial activation in these mice revealed a dose-dependent reduction in males but not in females. In summary, radiation-induced, long-term changes in behavior and pathology, although modest, appear specific to both sex and the underlying disease state.

Space radiation presents a substantial threat to travel beyond Earth. Relatively low doses of high-energy particle radiation cause physiological and behavioral impairments in rodents and may pose risks to human spaceflight. There is evidence that 56Fe irradiation, a significant component of space radiation, may be more harmful to males than to females and worsen Alzheimer’s disease pathology in genetically vulnerable models. Yet, research on the long-term, sex- and genotype-specific effects of 56Fe irradiation is lacking. Here, we irradiated 4-month-old male and female, wild-type and Alzheimer’s-like APP/PS1 mice with 0, 0.10, or 0.50 Gy of 56Fe ions (1GeV/u). Mice underwent microPET scans before and 7.5 months after irradiation, a battery of behavioral tests at 11 months of age and were sacrificed for pathological and biochemical analyses at 12 months of age. 56Fe irradiation worsened amyloid-beta (Aβ) pathology, gliosis, neuroinflammation and spatial memory, but improved motor coordination, in male transgenic mice and worsened fear memory in wild-type males. Although sham-irradiated female APP/PS1 mice had more cerebral Aβ and gliosis than sham-irradiated male transgenics, female mice of both genotypes were relatively spared from radiation effects 8 months later. These results provide evidence for sex-specific, long-term CNS effects of space radiation.

NRC publication: Yes

The Wilkinson Microwave Anisotropy Probe (WMAP) mapped the distribution of temperature and polarization over the entire sky in five microwave frequency bands. These full-sky maps were used to obtain measurements of temperature and polarization anisotropy of the cosmic microwave background with unprecedented accuracy and precision. The analysis of two-point correlation functions of temperature and polarization data gives determinations of the fundamental cosmological parameters such as the age and composition of the universe, as well as the key parameters describing the physics of inflation, which is further constrained by three-point correlation functions. WMAP observations alone reduced the flat $\\Lambda $ cold dark matter ($\\Lambda $CDM) cosmological model (six) parameter volume by a factor of $>$68,000 compared with pre-WMAP measurements. The WMAP observations (sometimes in combination with other astrophysical probes) convincingly show the existence of non-baryonic dark matter, the cosmic neutrino background, the flatness of the spatial geometry of the universe, a deviation from a scale-invariant spectrum of initial scalar fluctuations, and that the current universe is undergoing an accelerated expansion. The WMAP observations provide the strongest ever support for inflation; namely, the structures we see in the universe originate from quantum fluctuations generated during inflation.

The exotic radiation permeating interplanetary space remains the least understood and perhaps most challenging intrinsic barrier to a sustained human presence beyond Earth. As the coming decade brings the promise of continuous lunar habitation and even the first voyage to another planet, spacefaring endeavors must contend with this ever present threat to human health. On Earth, as medical advances continue to extend human life and radiation becomes an increasingly potent tool for medical diagnostics and treatment, we are increasingly confronted by our lack of knowledge on long term health effects and disease interactions of low dose - and in the case of cancer radiotherapy not so low dose - radiation exposure.The goal of this dissertation is to explore and develop both new and existing in vitro neural models for radiation research – particularly in the context of neurodegenerative disease. First, we adapt an existing 3D in vitro model of Alzheimer’s disease, which captures the beta-amyloid (Aβ) and phosphorylated tau protein aggregation characteristic of the disease, for use with the particle accelerator facility at the NASA Space Radiation Laboratory (NSRL). We show consistent changes in Alzheimer’s protein pathology and marked differences in RNA transcription dependent on culture genotype and radiation type. Then we expand on that model, leveraging the flexibility of in vitro systems to incorporate a microglial migration assay and to better model the low fluence nature of the space radiation environment while still retaining compatibility with the NSRL accelerator. We then show proof-of-concept for an accelerator-compatible, rapid differentiation neuron astrocyte coculture model derived from human induced pluripotent stem cells in which we investigate the impact of allelic variants in the APOE gene on the interaction between radiation exposure and Alzheimer’s-relevant proteins and RNA transcription. Finally, we explore the development of an ex vivo organotypic brain slice culture model and the challenges to and benefits of adapting such a platform for use with microbeam accelerators.This work develops approaches to improve both the biological fidelity and the irradiation fidelity of these model systems with the overall goal of creating better tools for investigating the long-term neural consequences of radiation exposure.

Magnetars are highly magnetized young neutron stars that occasionally produce enormous bursts and flares of X-rays and gamma-rays. Of the approximately thirty magnetars currently known in our Galaxy and Magellanic Clouds, five have exhibited transient radio pulsations. Fast radio bursts (FRBs) are millisecond-duration bursts of radio waves arriving from cosmological distances. Some have been seen to repeat. A leading model for repeating FRBs is that they are extragalactic magnetars, powered by their intense magnetic fields. However, a challenge to this model has been that FRBs must have radio luminosities many orders of magnitude larger than those seen from known Galactic magnetars. Here we report the detection of an extremely intense radio burst from the Galactic magnetar SGR 1935+2154 using the Canadian Hydrogen Intensity Mapping Experiment (CHIME) FRB project. The fluence of this two-component bright radio burst and the estimated distance to SGR 1935+2154 together imply a 400-800 MHz burst energy of \\(\\sim 3 \\times 10^{34}\\) erg, which is three orders of magnitude brighter than those of any radio-emitting magnetar detected thus far. Such a burst coming from a nearby galaxy would be indistinguishable from a typical FRB. This event thus bridges a large fraction of the radio energy gap between the population of Galactic magnetars and FRBs, strongly supporting the notion that magnetars are the origin of at least some FRBs.