154 research outputs found
Impact of Spaceflight and Artificial Gravity on the Mouse Retina: Biochemical and Proteomic Analysis
Astronauts are reported to have experienced some impairment in visual acuity during their mission on the International Space Station (ISS) and after they returned to Earth. There is emerging evidence that changes in vision may involve alterations in ocular structure and function. To investigate possible mechanisms, changes in protein expression profiles and oxidative stress-associated apoptosis were examined in mouse ocular tissue after spaceflight. Nine-week-old male C57BL/6 mice (n = 12) were launched from the Kennedy Space Center on a SpaceX rocket to the ISS for a 35-day mission. The animals were housed in the mouse Habitat Cage Unit (HCU) in the Japan Aerospace Exploration Agency (JAXA) âKiboâ facility on the ISS. The flight mice lived either under an ambient microgravity condition (”g) or in a centrifugal habitat unit that produced 1 g artificial gravity (”g + 1 g). Habitat control (HC) and vivarium control mice lived on Earth in HCUs or normal vivarium cages, respectively. Quantitative assessment of ocular tissue demonstrated that the ”g group induced significant apoptosis in the retina vascular endothelial cells compared to all other groups (p < 0.05) that was 64% greater than that in the HC group. Proteomic analysis showed that many key pathways responsible for cell death, cell repair, inflammation, and metabolic stress were significantly altered in ”g mice compared to HC animals. Additionally, there were more significant changes in regulated protein expression in the ”g group relative to that in the ”g + 1 g group. These data provide evidence that spaceflight induces retinal apoptosis of vascular endothelial cells and changes in retinal protein expression related to cellular structure, immune response and metabolic function, and that artificial gravity (AG) provides some protection against these changes. These retinal cellular responses may affect bloodâretinal barrier (BRB) integrity, visual acuity, and impact the potential risk of developing late retinal degeneration
Polycystic Kidney Disease in the Medaka (Oryzias latipes) pc Mutant Caused by a Mutation in the Gli-Similar3 (glis3) Gene
Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients
Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain
Spaceflight entails various stressful environmental factors including microgravity. The effects of gravity changes have been studied extensively on skeletal, muscular, cardiovascular, immune and vestibular systems, but those on the nervous system are not well studied. The alteration of gravity in ground-based animal experiments is one of the approaches taken to address this issue. Here we investigated the effects of centrifugation-induced gravity changes on gene expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors (5-HTRs) in the mouse brain. Exposure to 2g hypergravity for 14 days showed differential modulation of gene expression depending on regions of the brain. BDNF expression was decreased in the ventral hippocampus and hypothalamus, whereas increased in the cerebellum. 5-HT1BR expression was decreased in the cerebellum, whereas increased in the ventral hippocampus and caudate putamen. In contrast, hypergravity did not affect gene expression of 5-HT1AR, 5-HT2AR, 5-HT2CR, 5-HT4R and 5-HT7R. In addition to hypergravity, decelerating gravity change from 2g hypergravity to 1g normal gravity affected gene expression of BDNF, 5-HT1AR, 5-HT1BR, and 5-HT2AR in various regions of the brain. We also examined involvement of the vestibular organ in the effects of hypergravity. Surgical lesions of the inner earâs vestibular organ removed the effects induced by hypergravity on gene expression, which suggests that the effects of hypergravity are mediated through the vestibular organ. In summary, we showed that gravity changes induced differential modulation of gene expression of BDNF and 5-HTRs (5-HT1AR, 5-HT1BR and 5-HT2AR) in some brain regions. The modulation of gene expression may constitute molecular bases that underlie behavioral alteration induced by gravity changes
Spin-Charge Separation in the Model: Magnetic and Transport Anomalies
A real spin-charge separation scheme is found based on a saddle-point state
of the model. In the one-dimensional (1D) case, such a saddle-point
reproduces the correct asymptotic correlations at the strong-coupling
fixed-point of the model. In the two-dimensional (2D) case, the transverse
gauge field confining spinon and holon is shown to be gapped at {\em finite
doping} so that a spin-charge deconfinement is obtained for its first time in
2D. The gap in the gauge fluctuation disappears at half-filling limit, where a
long-range antiferromagnetic order is recovered at zero temperature and spinons
become confined. The most interesting features of spin dynamics and transport
are exhibited at finite doping where exotic {\em residual} couplings between
spin and charge degrees of freedom lead to systematic anomalies with regard to
a Fermi-liquid system. In spin dynamics, a commensurate antiferromagnetic
fluctuation with a small, doping-dependent energy scale is found, which is
characterized in momentum space by a Gaussian peak at (, ) with
a doping-dependent width (, is the doping
concentration). This commensurate magnetic fluctuation contributes a
non-Korringa behavior for the NMR spin-lattice relaxation rate. There also
exits a characteristic temperature scale below which a pseudogap behavior
appears in the spin dynamics. Furthermore, an incommensurate magnetic
fluctuation is also obtained at a {\em finite} energy regime. In transport, a
strong short-range phase interference leads to an effective holon Lagrangian
which can give rise to a series of interesting phenomena including linear-
resistivity and Hall-angle. We discuss the striking similarities of these
theoretical features with those found in the high- cuprates and give aComment: 70 pages, RevTex, hard copies of 7 figures available upon request;
minor revisions in the text and references have been made; To be published in
July 1 issue of Phys. Rev. B52, (1995
Colossal Magnetoresistant Materials: The Key Role of Phase Separation
The study of the manganese oxides, widely known as manganites, that exhibit
the ``Colossal'' Magnetoresistance (CMR) effect is among the main areas of
research within the area of Strongly Correlated Electrons. After considerable
theoretical effort in recent years, mainly guided by computational and
mean-field studies of realistic models, considerable progress has been achieved
in understanding the curious properties of these compounds. These recent
studies suggest that the ground states of manganite models tend to be
intrinsically inhomogeneous due to the presence of strong tendencies toward
phase separation, typically involving ferromagnetic metallic and
antiferromagnetic charge and orbital ordered insulating domains. Calculations
of the resistivity versus temperature using mixed states lead to a good
agreement with experiments. The mixed-phase tendencies have two origins: (i)
electronic phase separation between phases with different densities that lead
to nanometer scale coexisting clusters, and (ii) disorder-induced phase
separation with percolative characteristics between equal-density phases,
driven by disorder near first-order metal-insulator transitions. The coexisting
clusters in the latter can be as large as a micrometer in size. It is argued
that a large variety of experiments reviewed in detail here contain results
compatible with the theoretical predictions. It is concluded that manganites
reveal such a wide variety of interesting physical phenomena that their
detailed study is quite important for progress in the field of Correlated
Electrons.Comment: 76 pages, 21 PNG files with figures. To appear in Physics Report
Development of new experimental platform âMARSââMultiple Artificial-gravity Research Systemâto elucidate the impacts of micro/partial gravity on mice
This Japan Aerospace Exploration Agency project focused on elucidating the impacts of partial gravity (partial g) and microgravity (ÎŒg) on mice using newly developed mouse habitat cage units (HCU) that can be installed in the Centrifuge-equipped Biological Experiment Facility in the International Space Station. In the first mission, 12 C57BL/6âJ male mice were housed under ÎŒg or artificial earth-gravity (1âg). Mouse activity was monitored daily via downlinked videos; ÎŒg mice floated inside the HCU, whereas artificial 1âg mice were on their feet on the floor. After 35 days of habitation, all mice were returned to the Earth and processed. Significant decreases were evident in femur bone density and the soleus/gastrocnemius muscle weights of ÎŒg mice, whereas artificial 1âg mice maintained the same bone density and muscle weight as mice in the ground control experiment, in which housing conditions in the flight experiment were replicated. These data indicate that these changes were particularly because of gravity. They also present the first evidence that the addition of gravity can prevent decreases in bone density and muscle mass, and that the new platform âMARSâ may provide novel insights on the molecular-mechanisms regulating biological processes controlled by partial g/ÎŒg
miR-3941: A novel microRNA that controls IGBP1 expression and is associated with malignant progression of lung adenocarcinoma
Immunoglobulin (CD79a) binding protein 1 (IGBP1) is universally overexpressed in lung adenocarcinoma and exerts an anti-apoptotic effect by binding to PP2Ac. However, the molecular mechanism of IGBP1 overexpression is still unclear. In the present study, we used a microRNA (miRNA) array and TargetScan Human software to detect IGBP1-related miRNAs that regulate IGBP1 expression. The miRNA array analysis revealed more than 100 miRNAs that are dysregulated in early invasive adenocarcinoma. On the other hand, in silico analysis using TargetScan Human revealed 79 miRNAs that are associated with IGBP1 protein expression. Among the miRNAs selected by miRNA array analysis, six (miR-34b, miR-138, miR-374a, miR-374b, miR-1909, miR-3941) were also included among those selected by TargetScan analysis. Real-time reverse transcription PCR (real-time RT-PCR) showed that the six microRNAs were downregulated in invasive adenocarcinoma (IGBP1+) relative to adjacent normal lung tissue (IGBP1â). Among these microRNAs, only miR-34b and miR-3941 depressed luciferase activity by targeting 3âČUTR-IGBP1 in the luciferase vector. We transfected miR-34b and miR-3941 into lung adenocarcinoma cell lines (A549, PC-9), and both of them suppressed IGBP1 expression and cell proliferation. Moreover, the transfected miR-34b and miR-3941 induced apoptosis of a lung adenocarcinoma cell line, similarly to the effect of siIGBP1 RNA. As well as miR-34b, we found that miR-3941 targeted IGBP1 specifically and was able to exclusively downregulate IGBP1 expression. These findings indicate that suppression of miR-3941 has an important role in the progression of lung adenocarcinoma at an early stage
The Hubbard model within the equations of motion approach
The Hubbard model has a special role in Condensed Matter Theory as it is
considered as the simplest Hamiltonian model one can write in order to describe
anomalous physical properties of some class of real materials. Unfortunately,
this model is not exactly solved except for some limits and therefore one
should resort to analytical methods, like the Equations of Motion Approach, or
to numerical techniques in order to attain a description of its relevant
features in the whole range of physical parameters (interaction, filling and
temperature). In this manuscript, the Composite Operator Method, which exploits
the above mentioned analytical technique, is presented and systematically
applied in order to get information about the behavior of all relevant
properties of the model (local, thermodynamic, single- and two- particle ones)
in comparison with many other analytical techniques, the above cited known
limits and numerical simulations. Within this approach, the Hubbard model is
shown to be also capable to describe some anomalous behaviors of the cuprate
superconductors.Comment: 232 pages, more than 300 figures, more than 500 reference
Down-regulation of GATA1-dependent erythrocyte-related genes in the spleens of mice exposed to a space travel
Secondary lymphoid organs are critical for regulating acquired immune responses. The aim of this study was to characterize the impact of spaceflight on secondary lymphoid organs at the molecular level. We analysed the spleens and lymph nodes from mice flown aboard the International Space Station (ISS) in orbit for 35 days, as part of a Japan Aerospace Exploration Agency mission. During flight, half of the mice were exposed to 1âg by centrifuging in the ISS, to provide information regarding the effect of microgravity and 1âg exposure during spaceflight. Whole-transcript cDNA sequencing (RNA-Seq) analysis of the spleen suggested that erythrocyte-related genes regulated by the transcription factor GATA1 were significantly down-regulated in ISS-flown vs. ground control mice. GATA1 and Tal1 (regulators of erythropoiesis) mRNA expression was consistently reduced by approximately half. These reductions were not completely alleviated by 1âg exposure in the ISS, suggesting that the combined effect of space environments aside from microgravity could down-regulate gene expression in the spleen. Additionally, plasma immunoglobulin concentrations were slightly altered in ISS-flown mice. Overall, our data suggest that spaceflight might disturb the homeostatic gene expression of the spleen through a combination of microgravity and other environmental changes
- âŠ