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5,794 results for “exposures”
miRNA signature detection and countermeasures against HZE radiation exposure for tissue degeneration-Liver tissue
Biological risks associated with space radiation and microgravity are major concerns for long-term space travel. Through a Systems Biology approach our previous NASA work has shown both TGF xce xb2 signaling pathways and miRNAs have a critical impact on defining health risks with and without space irradiation. We hypothesize that circulating microRNA (miRNA) signatures are driving microvascular disease and muscle degeneration associated with accelerating aging and will be enhanced by exposure to the space environment (radiation and microgravity). We investigated this hypothesis both in vivo and in vitro and test novel antagonist therapies to these miRNA signatures as countermeasures to reduce space radiation-induced health risks. A comprehensive Systems Biology approach was used to examine the influence by high atomic number by high (H) atomic number (Z) and energy (E) (HZE) irradiation. To simulate low-dose exposure due to galactic cosmic rays (GCR) we used the ions energy and doses determined by a NASA consensus formula of 7 different ions to represent GCR (referred to as GCR sim model). To simulate high-dose radiation exposure due to solar particle events (SPE) we used an acute dose of SPE simulated beam at 1Gy which has energies ranging from 50MeV to 150MeV. C57BL/6 wild-type mice were utilized for irradiation with our established simulated microgravity model (hindlimb suspension model) and an in vitro 3D microvasculature tissue model under simulated microgravity (clinostat) conditions will also be irradiated. To expand on the circulating miRNA signature determined from our preliminary data we determined a group of conserved miRNAs which are commonly being regulated in the majority of the organs and tissues throughout the host using our established techniques. MiRNA-sequencing on serum (before IR and at time of sacrifice) liver heart and muscle tissue for all radiation groups revealed the key circulating miRNA signature (consisting of multiple miRNAs) impacting disease risk. Collectively understanding of how whole body space radiation impacts microvascular and tissue degeneration through circulating miRNAs will greatly enhance health risk prognostication and provide possible new mechanisms for protection against space radiation.
miRNA signature detection and countermeasures against HZE radiation exposure for tissue degeneration-Heart tissue
Biological risks associated with space radiation and microgravity are major concerns for long-term space travel. Through a Systems Biology approach our previous NASA work has shown both TGF xce xb2 signaling pathways and miRNAs have a critical impact on defining health risks with and without space irradiation. We hypothesize that circulating microRNA (miRNA) signatures are driving microvascular disease and muscle degeneration associated with accelerating aging and will be enhanced by exposure to the space environment (radiation and microgravity). We investigated this hypothesis both in vivo and in vitro and test novel antagonist therapies to these miRNA signatures as countermeasures to reduce space radiation-induced health risks. A comprehensive Systems Biology approach was used to examine the influence by high atomic number by high (H) atomic number (Z) and energy (E) (HZE) irradiation. To simulate low-dose exposure due to galactic cosmic rays (GCR) we used the ions energy and doses determined by a NASA consensus formula of 7 different ions to represent GCR (referred to as GCR sim model). To simulate high-dose radiation exposure due to solar particle events (SPE) we used an acute dose of SPE simulated beam at 1Gy which has energies ranging from 50MeV to 150MeV. C57BL/6 wild-type mice were utilized for irradiation with our established simulated microgravity model (hindlimb suspension model) and an in vitro 3D microvasculature tissue model under simulated microgravity (clinostat) conditions will also be irradiated. To expand on the circulating miRNA signature determined from our preliminary data we determined a group of conserved miRNAs which are commonly being regulated in the majority of the organs and tissues throughout the host using our established techniques. MiRNA-sequencing on serum (before IR and at time of sacrifice) liver heart and muscle tissue for all radiation groups revealed the key circulating miRNA signature (consisting of multiple miRNAs) impacting disease risk. Collectively understanding of how whole body space radiation impacts microvascular and tissue degeneration through circulating miRNAs will greatly enhance health risk prognostication and provide possible new mechanisms for protection against space radiation.
Identifying radiation exposure biomarkers from mouse blood transcriptome
Here we present a whole-genome survey of the murine transcriptomic response to physiologically-relevant radiation doses 2 and 8 Gy. There are 18 distinct biological samples here. Mice were exposed to ionizing radiation (Cesium-138 source) and whole blood was collected by cardiac puncture 6 hours post treatment. Doses were 0 (7 samples) 2 (5 samples) and 8 (6 samples) gy.
Expression profiling of murine lung 70 days following exposure to fractionated or acute dose of 1.0 Gy 56Fe- particle irradiation
Irradiation of the K-rasLA1 mouse model with a fractionated dose of 1.0Gy 56Fe- particles increases the incidence of invasive carcinoma compared to unirradiated controls or those irradiated with an acute dose. Microarray profiling was perfromed on whole lungs from K-rasLA1 mice in order to determine global expression changes in the lung following radiation exposure. RNA was extracted from K-rasLA1 lungs from unirradiated control animals or those irradiated with a fractionated or acute dose of 1.0Gy 56Fe- particles 70 days post-irradiation when lungs are still histologically indistiguishable and only contain benign lesions. 129S2 K-rasLA1 mice were either irradiated with an acute (1.0Gy x1; n = 15) or fractionated (0.2Gy x5; n=13) dose of 1.0Gy 56Fe- particles or left unirradiated (n=13). Animals were euthanized 70 days post-irradiation and RNA was extracted from the whole left lung of each animal.
Gene responses in mouse brain to long-term exposure to microgravity
The spaceflight experiment was carried out using male C57BL/10J mice (8 weeks old at launch). Wild type mice (n=3) were launched by Space Shuttle Discovery and housed on the International Space Station (ISS) for 91 days. They returned to the Earth by Space Shuttle Atlantis. But only one mouse returned to the Earth alive. Whole brain was sampled from the mouse killed by inhalation of carbon dioxide at the Life Sciences Support Facility of Kennedy Space Center within 3-4 hours after landing. After the spaceflight experiment the on-ground experiment was also carried out at the Advanced Biotechnology Center in Genova Italy. A mouse with the same species sex and age was housed in mice drawer system (MDS) which was utilized for the spaceflight (SF) mice for 3 months as the ground control (GC). Another mouse was housed in normal vivarium cage as the laboratory control (LC). Amount of food and water supplementation and environmental conditions were simulated as the flight group. After 3 months brain was sampled from one mouse in group GC and LC respectively. Comprehensive analyses of gene expression were performed in the right brain. Total of 4,000 genes were analyzed. The expression levels of 60 genes significantly changed in response to SF compared with LC and/or GC. The 15 and 16 genes were up- (> 2 folds) and down-regulated (< 0.5 folds) respectively following SF vs. GC. The levels of 58 genes were significantly altered by housing in MDS in space and/or on the ground. Forty seven and 11 genes were significantly up- and down-regulated vs. LC. Twenty seven out of these genes responded to caging in MDS both in space and on the ground. Further 31 genes were influenced by housing in MDS on the Earth. Responses of the characteristics of brain to long-term gravitational unloading were investigated in mice.
Transcriptome Profiles in Normal Human Bronchial Epithelial Cells after Exposure to gamma-rays and different HZE particles
Distinct transcriptome profiles in response to low-LET and high-LET and different radiation qualities of HZE particles. Total RNA obtained from HBEC3KT cells after 1 4 12 and 24 hours of radiation. Mock-irradiated samples at each time point and control samples before radiation (0 hour) were also collected.
Bystander response to 2.5 Gy of protons in a human 3-dimensional skin model in 16 h after exposure
Bystander mechanisms that originate in the areas surrounding a tissue damage presumably play an important role participating in wound healing and tissue remodeling. Thus identification and characterization of bystander mechanisms will help to development of new treatments of patients with a radiation exposure. In the present study we irradiated 3-dimensional tissue model of human epidermis Epi-200 (Mat-Tek Ashland MA) with 2.5 Gy protons. By exposing only a thin strip across the center of the EPI-200 tissue we have been able to measure global gene expression responses in directly irradiated and bystander cells located at 0.125-0.375 0.375-0.625 0.625-875 mm from the irradiation line. The data were analyzed using BRB-Array Tools (NIH) and further gene ontology analysis and network analysis was performed with Panther (Applied Biosystems) and IPA (Ingenuity) accordingly. Significantly responding genes were identified at all distances and included sets common to both direct and bystander responses. False discovery rate in bystander samples did not exceed 20% (p=0.001) and was sufficiently low in the samples obtained after the whole tissue exposure (0.06-1.16%). Analysis of the fragments cut at the same distance revealed 52 54 and 88 differentially expressed genes. These gene lists overlapped each other had from 3 to 12 genes in common including CLED2 S100A7A. Samples obtained after the whole tissue exposure discovered 949 differentially expressed genes. Moreover the performed gene ontology analysis showed there overrepresentation of TP53 pathway (pathways p=2.04E-02) a common marker of direct irradiation response and also overrepresentation of the following groups of genes: signal transduction (p=4.52E-04) cell communication (p=1.24E-04) and cell cycle in the category of biological processes; DNA helicase activity (p=2.54E-07) receptor binding (p=6.19E-04) calcium ion binding proteins (p=2.57E-03) as the molecular functions. Differentially expresses genes of bystander samples had few categories in common such as cell communication (p=2.36E-03) and signal transduction (p=2.42E-03) among the biological processes and receptor activity (p=4.54E-03) among the molecular functions. Categories specific for the bystander samples included G-protein coupled receptors (p=7.24E-03) and ligand-gated ion channels (p=4.16E-03) suggesting a role of external stimulation and ion trafficking in bystander mechanisms. Radiation induced gene expression in 3-dimensional tissue model Epi-200 was measured in 16 hours after exposure to 2.5 Gy of protons. Four independent experiments were performed for the samples collected at different distances from the irradiation line (125-375 375-625 and 625-875 micrometers) using three tissue fragments per a data point. Moreover three sets of whole tissue irradited samples were also generated for 0 and 2.5 Gy (6 samples total) and used for comparison of bystander and direct responses.
Exposure of zebrafish larvae to relative microgravity between 5-6 days post-fertilization
The general objective of the study was to determine modulation of gene expression by environmental factors with a special emphasis on bone formation. For this reason the specific period of treatment was chosen between 5-6 days post-fertilization (dpf) when bone formation and calcification are taking place. This experiment was designed as a new type of gravitational experiment which we like to call relative microgravity referring to the fact that the larvae first grow in hyper gravity for 5 days and are then returned to 1g normal gravity for 1 day. Zebrafish embryos were placed on a Large Diameter Centrifuge at 3 hpf brought to a gravitational force of 3 g until 5 dpf. Reference embryos were kept in parallel at 1g (Inc). At 5dpf one batch was left at 3g (3g) one batch was returned to 1g (3g>1g) while a third batch was returned to 1g but left on the axis of the centrifuge (Axe; 3g>Axe). The experiment was repeated 4 times each time with 4 batches of 60 larvae.
Exposure of zebrafish larvae to 3g and 5g hyper gravity between 5-6 days post-fertilization.
The general objective of the study was to determine modulation of gene expression by environmental factors, with a special emphasis on bone formation. For this reason, the specific period of treatment was chosen between 5-6 days post-fertilization (dpf), when bone formation and calcification are taking place. Zebrafish larvae were placed at 5 dpf into a Large Diameter Centrifuge and brought to a gravitational force of 3g or 5g for 24 hours. We show that this treatment causes a clear increase of bone formation, as illustrated by cranial skeleton staining of the bone matrix by Alizarin Red, by morphometric analysis of the resulting images and by gene expression studies of selected genes. Thus, a whole genome micro-array experiment was conducted to identify genes that may be involved in the observed effect on bone formation.
['Mlh1 deficiency increases the risk of hematopoietic malignancy after simulated space radiation exposure']
['Cancer-causing genome instability is a major concern during space travel due to exposure of astronauts to potent sources of high-linear energy transfer (LET) ionizing radiation. Hematopoietic stem cells (HSCs) are particularly susceptible to genotoxic stress, and accumulation of damage can lead to HSC dysfunction and oncogenesis. Our group recently demonstrated that aging human HSCs accumulate microsatellite instability coincident with loss of MLH1, a DNA Mismatch Repair (MMR) protein, which could reasonably predispose to radiation-induced HSC malignancies. Therefore, in an effort to reduce risk uncertainty for cancer development during deep space travel, we employed an Mlh1+/- mouse model to study the effects high-LET 56Fe ion space-like radiation. Irradiated Mlh1+/- mice showed a significantly higher incidence of lymphomagenesis with 56Fe ions compared to γ-rays and unirradiated mice, and malignancy correlated with increased MSI in the tumors. In addition, whole-exome sequencing analysis revealed high SNVs and INDELs in lymphomas being driven by loss of Mlh1 and frequently mutated genes had a strong correlation with human leukemias. Therefore, the data suggest that age-related MMR deficiencies could lead to HSC malignancies after space radiation, and that countermeasure strategies will be required to adequately protect the astronaut population on the journey to Mars.']
miRNA signature detection and countermeasures against HZE radiation exposure for tissue degeneration-Soleus muscle
Biological risks associated with space radiation and microgravity are major concerns for long-term space travel. Through a Systems Biology approach our previous NASA work has shown both TGF xce xb2 signaling pathways and miRNAs have a critical impact on defining health risks with and without space irradiation. We hypothesize that circulating microRNA (miRNA) signatures are driving microvascular disease and muscle degeneration associated with accelerating aging and will be enhanced by exposure to the space environment (radiation and microgravity). We investigated this hypothesis both in vivo and in vitro and test novel antagonist therapies to these miRNA signatures as countermeasures to reduce space radiation-induced health risks. A comprehensive Systems Biology approach was used to examine the influence by high atomic number by high (H) atomic number (Z) and energy (E) (HZE) irradiation. To simulate low-dose exposure due to galactic cosmic rays (GCR) we used the ions energy and doses determined by a NASA consensus formula of 7 different ions to represent GCR (referred to as GCR sim model). To simulate high-dose radiation exposure due to solar particle events (SPE) we used an acute dose of SPE simulated beam at 1Gy which has energies ranging from 50MeV to 150MeV. C57BL/6 wild-type mice were utilized for irradiation with our established simulated microgravity model (hindlimb suspension model) and an in vitro 3D microvasculature tissue model under simulated microgravity (clinostat) conditions will also be irradiated. To expand on the circulating miRNA signature determined from our preliminary data we determined a group of conserved miRNAs which are commonly being regulated in the majority of the organs and tissues throughout the host using our established techniques. MiRNA-sequencing on serum (before IR and at time of sacrifice) liver heart and muscle tissue for all radiation groups revealed the key circulating miRNA signature (consisting of multiple miRNAs) impacting disease risk. Collectively understanding of how whole body space radiation impacts microvascular and tissue degeneration through circulating miRNAs will greatly enhance health risk prognostication and provide possible new mechanisms for protection against space radiation.
Gene expression in blood of mice with internal exposure to Cs-137
Cesium-137 is a radionuclide of concern in fallout from reactor accidents or nuclear detonations. When ingested or inhaled it can expose the entire body for an extended period of time potentially contributing to serious health consequences ranging from acute radiation syndrome to increased cancer risks. In order to identify changes in gene expression that may be informative for detecting such exposure and to begin examining the molecular responses involved we have profiled global gene expression in mice injected with 137CsCl. We extracted RNA from the blood of control or 137CsCl-injected mice at 2 3 5 20 or 30 days after exposure. Gene expression was measured using Agilent Whole Mouse Genome Microarrays and the data was analyzed using BRB-ArrayTools. Three-month old male C57Bl/6 mice were injected intraperitoneally with 8.0 xc2 xb1 0.3 MBq 137CsCl solution in a volume of 50 xce xbcL or left as controls. Groups of treated and control mice were sacrificed at intervals during the first 2-30 days after exposure and total blood was collected using cardiac puncture. RNA was extracted from the blood globin-transcript reduced and subjected to whole genome expression microarray analysis.
Impact of radiation dose and time since radiation exposure on host-microbe relationship
GEO Series GSE244571. Mus musculus. 38 samples. Type: Other.
Transcriptome changes in response to lead exposure
GEO Series GSE65334. Arabidopsis thaliana; Hirschfeldia incana. 12 samples. Type: Expression profiling by array.
Phenotypically-anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish
GEO Series GSE80955. Danio rerio. 8 samples. Type: Expression profiling by array.
Molecular profiles and urinary biomarkers of upper tract urothelial carcinomas associated with aristolochic acid exposure [miRNA_tissue]
GEO Series GSE166907. Homo sapiens. 52 samples. Type: Expression profiling by RT-PCR.
The acute effects of methoxyacetic acid exposure on testis gene expression
GEO Series GSE10032. Rattus norvegicus. 47 samples. Type: Expression profiling by array.
Lack of hepatic response of microRNA in mice following DB[a,h]A exposure (Agilent expression)
GEO Series GSE35215. Mus musculus. 19 samples. Type: Expression profiling by array.
Perinatal exposure to an environmentally-relevant mixture of BFRs and ovarian gene expression in the adult rat
GEO Series GSE113000. Rattus norvegicus. 20 samples. Type: Expression profiling by array.
In vitro exposure of leukocytes to HIV pre-exposure prophylaxis (PrEP) decreases mitochondrial function and alters gene expression profiles.
GEO Series GSE159339. Homo sapiens. 15 samples. Type: Expression profiling by high throughput sequencing.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.