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1.
Appl Microbiol Biotechnol ; 105(20): 8009-8018, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34553250

RESUMO

While Saccharomyces cerevisiae is a popular organism to produce ethanol, its fermentation performance is affected at high sugar concentrations due to osmotic stress. We hypothesized that adaptation under ionic stress conditions will improve the fermentation performance at high sugar concentrations due to cross-stress adaptation. We, therefore, adapted a high-performance yeast strain, S. cerevisiae CEN.PK 122, to increasing salt concentrations in an industrial medium. Control cells were adapted in the medium without added salt. The cells adapted to 3.5% (w/v) salt concentration demonstrated a superior performance when fermenting 10-30% (w/v) glucose. When fermenting 30% (w/v) glucose, the ethanol yields of the adapted cells (0.49 ± 0.01 g g-1) were about 30% higher than the control cells (0.37 ± 0.01 g g-1) and are comparable with the best reported to date for any medium employed. Similar improvements were also observed when fermenting 10% (w/v) sucrose. However, little improvement in fermentation was observed at the higher temperature tested (40 °C), even though the growth of the adapted cells was greater when tested in YPD medium. The improvements in fermentation at 30 °C were primarily related to the faster growth of the adapted cells and not to an increase in specific intake rates. Additionally, a significantly reduced lag phase was also observed when fermenting 30% (w/v) glucose. Thus, our work shows the application of a simple strategy to significantly improve high-gravity fermentation (HGF) performance through adaptation. KEY POINTS: • Cell adapted on 3.5% NaCl made 28% more ethanol when fermenting 30% glucose. • The adapted cells had reduced lag phase, grew faster, and produced less glycerol. • The improvements were not related to increased specific rates of production.


Assuntos
Hipergravidade , Saccharomyces cerevisiae , Adaptação Fisiológica , Etanol , Fermentação
2.
Sci Rep ; 11(1): 17420, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465851

RESUMO

Gravity alteration is one of the critical environmental factors in the space, causing various abnormal behaviors related with the malfunctioned vestibular system. Due to the high plastic responses in the central vestibular system, the behavioral failures were resolved in a short period of time (in approx. 72 h). However, the plastic neurotransmission underlying the functional recovery is still elusive. To understand the neurotransmitter-induced plasticity under hypergravity, the extracellular single neuronal recording and the immunohistochemistry were conducted in the vestibular nucleus (VN). The animals were grouped as control, 24-h, 72-h, and 15-day exposing to 4G-hypergravity, and each group had two subgroups based on the origins of neuronal responses, such as canal and otolith. The averaged firing rates in VN showed no significant difference in the subgroups (canal-related: p > 0.105, otolith-related: p > 0.138). Meanwhile, the number of NMDAr was significantly changed by the exposing duration to hypergravity. The NMDAr decreased in 24 h (p = 1.048 × 10-9), and it was retrieved in 72 h and 15 days (p < 4.245 × 10-5). Apparently, the reduction and the retrieval in the number of NMDAr were synchronized with the generation and recovery of the abnormal behaviors. Thus, the plasticity to resolve the hypergravity-induced malfunctional behaviors was conducted by regulating the number of NMDAr.


Assuntos
Comportamento Animal , Regulação da Expressão Gênica , Hipergravidade , Plasticidade Neuronal , Neurônios/patologia , Receptores de N-Metil-D-Aspartato/metabolismo , Núcleos Vestibulares/patologia , Animais , Masculino , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Núcleos Vestibulares/metabolismo
3.
Int J Mol Sci ; 22(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34445156

RESUMO

Cellular responses to micro- and hypergravity are rapid and complex and appear within the first few seconds of exposure. Transcriptomic analyses are a valuable tool to analyze these genome-wide cellular alterations. For a better understanding of the cellular dynamics upon altered gravity exposure, it is important to compare different time points. However, since most of the experiments are designed as endpoint measurements, the combination of cross-experiment meta-studies is inevitable. Microarray and RNA-Seq analyses are two of the main methods to study transcriptomics. In the field of altered gravity research, both methods are frequently used. However, the generation of these data sets is difficult and time-consuming and therefore the number of available data sets in this research field is limited. In this study, we investigated the comparability of microarray and RNA-Seq data and applied the results to a comparison of the transcriptomics dynamics between the hypergravity conditions during two real flight platforms and a centrifuge experiment to identify temporal adaptation processes. We performed a comparative study on an Affymetrix HTA2.0 microarray and a paired-end RNA-Seq data set originating from the same Jurkat T cell RNA samples from a short-term hypergravity experiment. The overall agreeability was high, with better sensitivity of the RNA-Seq analysis. The microarray data set showed weaknesses on the level of single upregulated genes, likely due to its normalization approach. On an aggregated level of biotypes, chromosomal distribution, and gene sets, both technologies performed equally well. The microarray showed better performance on the detection of altered gravity-related splicing events. We found that all initially altered transcripts fully adapted after 15 min to hypergravity and concluded that the altered gene expression response to hypergravity is transient and fully reversible. Based on the combined multiple-platform meta-analysis, we could demonstrate rapid transcriptional adaptation to hypergravity, the differential expression of the ATPase subunits ATP6V1A and ATP6V1D, and the cluster of differentiation (CD) molecules CD1E, CD2AP, CD46, CD47, CD53, CD69, CD96, CD164, and CD226 in hypergravity. We could experimentally demonstrate that it is possible to develop methodological evidence for the meta-analysis of individual data.


Assuntos
Hipergravidade , Linfócitos T/metabolismo , Transcriptoma , Humanos , Células Jurkat , RNA-Seq , Voo Espacial , Ativação Transcricional
4.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201720

RESUMO

Microgravity acts on cellular systems on several levels. Cells of the immune system especially react rapidly to changes in gravity. In this study, we performed a correlative metabolomics analysis on short-term and long-term microgravity effects on primary human macrophages. We could detect an increased amino acid concentration after five minutes of altered gravity, that was inverted after 11 days of microgravity. The amino acids that reacted the most to changes in gravity were tightly clustered. The observed effects indicated protein degradation processes in microgravity. Further, glucogenic and ketogenic amino acids were further degraded to Glucose and Ketoleucine. The latter is robustly accumulated in short-term and long-term microgravity but not in hypergravity. We detected highly dynamic and also robust adaptative metabolic changes in altered gravity. Metabolomic studies could contribute significantly to the understanding of gravity-induced integrative effects in human cells.


Assuntos
Hipergravidade/efeitos adversos , Macrófagos/metabolismo , Metaboloma , Voo Espacial , Ausência de Peso/efeitos adversos , Células Cultivadas , Humanos
5.
Sci Rep ; 11(1): 15303, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315977

RESUMO

Hypergravity-an evolutionarily novel environment has been exploited to comprehend the response of living organisms including plants in the context of extra-terrestrial applications. Recently, researchers have shown that hypergravity induces desired phenotypic variability in seedlings. In the present study, we tested the utility of hypergravity as a novel tool in inducing reliable phenotype/s for potential terrestrial crop improvement applications. To investigate, bread wheat seeds (UAS-375 genotype) were subjected to hypergravity treatment (10×g for 12, and 24 h), and evaluated for seedling vigor and plant growth parameters in both laboratory and greenhouse conditions. It was also attempted to elucidate the associated biochemical and hormonal changes at different stages of vegetative growth. Resultant data revealed that hypergravity treatment (10×g for 12 h) significantly enhanced root length, root volume, and root biomass in response to hypergravity. The robust seedling growth phenotype may be attributed to increased alpha-amylase and TDH enzyme activities observed in seeds treated with hypergravity. Elevated total chlorophyll content and Rubisco (55 kDa) protein expression across different stages of vegetative growth in response to hypergravity may impart physiological benefits to wheat growth. Further, hypergravity elicited robust endogenous phytohormones dynamics in root signifying altered phenotype/s. Collectively, this study for the first time describes the utility of hypergravity as a novel tool in inducing reliable root phenotype that could be potentially exploited for improving wheat varieties for better water usage management.


Assuntos
Produtos Agrícolas/fisiologia , Hipergravidade , Raízes de Plantas/fisiologia , Triticum/fisiologia , Irrigação Agrícola , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Triticum/enzimologia , Triticum/crescimento & desenvolvimento , Triticum/metabolismo , Água/química
6.
Molecules ; 26(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066886

RESUMO

Gravity constituted the only constant environmental parameter, during the evolutionary period of living matter on Earth. However, whether gravity has affected the evolution of species, and its impact is still ongoing. The topic has not been investigated in depth, as this would require frequent and long-term experimentations in space or an environment of altered gravity. In addition, each organism should be studied throughout numerous generations to determine the profound biological changes in evolution. Here, we review the significant abnormalities presented in the cardiovascular, immune, vestibular and musculoskeletal systems, due to altered gravity conditions. We also review the impact that gravity played in the anatomy of snakes and amphibians, during their evolution. Overall, it appears that gravity does not only curve the space-time continuum but the biological continuum, as well.


Assuntos
Evolução Biológica , Fenômenos Fisiológicos Cardiovasculares , Hipergravidade , Sistema Imunitário/fisiologia , Fenômenos Fisiológicos Musculoesqueléticos , Glândula Tireoide/fisiologia , Vestíbulo do Labirinto/fisiologia , Ausência de Peso , Animais , Humanos , Voo Espacial
7.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063126

RESUMO

Hypergravity conditions may subject the kidney to intrinsic stress and lead to hemodynamic kidney dysfunction. However, the mechanisms underlying this phenomenon remain unclear. Accumulation of unfolded proteins in the endoplasmic reticulum (i.e., ER stress) is often observed in kidney diseases. Therefore, this study investigated whether hypergravity stress alters acetaminophen-induced renal toxicity in vivo, as well as the molecular mechanisms involved in this process. C57BL/6 mice were submitted to one or three loads of +9 Gx hypergravity for 1 h with or without acetaminophen (APAP) treatment. The protein levels of cell survival markers, including pAKT and pCREB, were decreased in the kidney after acetaminophen treatment with a single hypergravity load. Additionally, the combined treatment increased kidney injury markers, serum creatinine, and Bax, Bcl2, and Kim-1 transcript levels and enhanced ER stress-related markers were further. Moreover, multiple hypergravity loads enabled mice to overcome kidney injury, as indicated by decreases in serum creatinine content and ER stress marker levels, along with increased cell viability indices. Similarly, multiple hypergravity loads plus APAP elevated miR-122 levels in the kidney, which likely originated from the liver, as the levels of primary miR-122 increased only in the liver and not the kidney. Importantly, this phenomenon may contribute to overcoming hypergravity-induced kidney injury. Taken together, our results demonstrate that APAP-exposed mice submitted to a single load of hypergravity exhibited more pronounced kidney dysfunction due to increased ER stress, which may be overcome by repetitive hypergravity loads presumably due to increased production of miR-122 in the liver. Thus, our study provides novel insights into the mechanisms by which hypergravity stress plus APAP medication induce kidney injury, which may be overcome by repeated hypergravity exposure.


Assuntos
Acetaminofen/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipergravidade , Rim/patologia , Fígado/metabolismo , MicroRNAs/genética , Animais , Estresse do Retículo Endoplasmático/genética , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo
8.
Sci Rep ; 11(1): 7267, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790394

RESUMO

Although immunotherapy holds promising cytotoxic activity against lymphoma or leukemia, the immunosuppressive mechanisms of solid tumors remain challenging. In this study, we developed and applied a hypergravity exposure system as a novel strategy to improve the responsiveness of breast cancer cells to natural killer (NK) cells for efficient immunotherapy. Following exposure to hypergravity, either in the presence or absence of NK cells, we investigated for changes in the cell cytoskeletal structure, which is related to the F-actin mediated immune evasion mechanism (referred to as "actin response") of cancer cells. Breast cancer cell line MDA-MB-231 cells were exposed thrice to a 20 min hypergravitational condition (10 × g), with a 20 min rest period between each exposure. The applied hypergravity induces changes in the intracellular cytoskeleton structure without decreasing the cell viability but increasing the cytotoxicity of MDA-MB-231 from 4 to 18% (4.5-fold) at a 3:1 ratio (NK-to-target). Analyses related to F-actin further demonstrate that the applied hypergravity results in rearrangement of the cytoskeleton, leading to inhibition of the actin response of MDA-MB-231. Taken together, our results suggest that the mechanical load increases through application of hypergravity, which potentially improves efficiency of cell-based immunotherapies by sensitizing tumors to immune cell-mediated cytotoxicity.


Assuntos
Actinas/imunologia , Neoplasias da Mama/imunologia , Hipergravidade , Células Matadoras Naturais/imunologia , Proteínas de Neoplasias/imunologia , Neoplasias da Mama/terapia , Citoesqueleto/imunologia , Feminino , Humanos , Imunoterapia , Células MCF-7 , Evasão Tumoral
9.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33803957

RESUMO

Using rotors to expose animals to different levels of hypergravity is an efficient means of understanding how altered gravity affects physiological functions, interactions between physiological systems and animal development. Furthermore, rotors can be used to prepare space experiments, e.g., conducting hypergravity experiments to demonstrate the feasibility of a study before its implementation and to complement inflight experiments by comparing the effects of micro- and hypergravity. In this paper, we present a new platform called the Gravitational Experimental Platform for Animal Models (GEPAM), which has been part of European Space Agency (ESA)'s portfolio of ground-based facilities since 2020, to study the effects of altered gravity on aquatic animal models (amphibian embryos/tadpoles) and mice. This platform comprises rotors for hypergravity exposure (three aquatic rotors and one rodent rotor) and models to simulate microgravity (cages for mouse hindlimb unloading and a random positioning machine (RPM)). Four species of amphibians can be used at present. All murine strains can be used and are maintained in a specific pathogen-free area. This platform is surrounded by numerous facilities for sample preparation and analysis using state-of-the-art techniques. Finally, we illustrate how GEPAM can contribute to the understanding of molecular and cellular mechanisms and the identification of countermeasures.


Assuntos
Hipergravidade/efeitos adversos , Roedores/fisiologia , Voo Espacial , Ausência de Peso/efeitos adversos , Animais , Humanos , Larva/patogenicidade , Larva/efeitos da radiação , Camundongos , Modelos Animais , Xenopus laevis/fisiologia
10.
Biogerontology ; 22(2): 237-251, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33665732

RESUMO

While severe stresses have deleterious effects, mild stresses can have beneficial effects called hormetic effects. This study observed survival time at 37.5 °C and at 13-16 days of age of wild-type Drosophila melanogaster flies and dFOXO mutants, after they were subjected to 5 or 10 min daily at 37.5 °C for 5 days starting at 5 days of age. This mild stress increased survival time of the mutants, this effect being nearly not observed in wild-type flies. Previous studies showed that another mild stress, the cold, can increase survival time to heat of wild-type flies, but not of dFOXO mutants, while hypergravity increased survival time of mutants but not of wild-type flies. Therefore, three mild stresses, cold, hypergravity, and heat can increase resistance to heat but the pathways mediating this effect are seemingly different, as cold does not increase resistance in dFOXO mutants but increases it in wild-type flies, while hypergravity and heat have opposite effects. It appears that dFOXO may be needed or not to observe hormetic effects.


Assuntos
Drosophila melanogaster , Hipergravidade , Animais , Drosophila melanogaster/genética , Resposta ao Choque Térmico/genética , Hormese , Longevidade/genética
11.
J Biotechnol ; 332: 1-10, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33741406

RESUMO

A stirred tank bioreactor (STR) coupled with two column bioreactors (CRs) was used for ethanol production from sweet sorghum stem juice by Saccharomyces cerevisiae SSJ01KKU in a very high gravity fermentation. The effects of the medium circulation rate between the STR and CRs (2.6 and 5.2 mL/min, corresponding to 25 and 50 % of the S. cerevisiae specific growth rate), the starting time of medium circulation (0 and 4 h) and cell inoculation were investigated. The results showed that a medium circulation rate of 5.2 mL/min, starting the medium circulation at the beginning of fermentation (0 h) with cell inoculation into the STR only were appropriate conditions for ethanol production. This yielded an average ethanol concentration (PE) of 120.96 g/L and ethanol productivity (QP) of 2.52 g/L⋅h. When a repeated-batch (RB) ethanol fermentation in the STR coupled with CR was carried out using a drain and fill technique at different volumes (75 and 90 %, referenced as RB1 and RB2, respectively), it was found that at least eight successive cycles could be operated under both RB1 and RB2. The average PE and QP for RB1 and RB2 were not significantly different. However, the average total ethanol production rate in RB2 (3.25 g/h) over the eight cycles was significantly higher than that of RB1 (2.60 g/h).


Assuntos
Hipergravidade , Sorghum , Reatores Biológicos , Etanol , Fermentação , Saccharomyces cerevisiae
12.
Eur J Pharm Biopharm ; 163: 38-48, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33785416

RESUMO

The oral administration of drugs remains a challenge due to rapid enzymatic degradation and minimal absorption in the gastrointestinal tract. Mechanical forces, namely hypergravity, can interfere with cellular integrity and drug absorption, and there is no study describing its influence in the intestinal permeability. In this work, it was studied the effect of hypergravity on intestinal Caco-2 cells and its influence in the intestinal permeability of different nanoformulations and molecules. It was shown that the cellular metabolic activity and integrity were maintained after exposure to different gravity-levels (g-levels). Expression of important drug transporters and tight junctions' proteins was evaluated and, most proteins demonstrated a switch of behavior in their expression. Furthermore, paracellular transport of FITC-Dextran showed to significantly increase with hypergravity, which agrees with the decrease of transepithelial electrical resistance and the increase of claudin-2 at higher g-levels. The diffusion of camptothecin released from polymeric micelles revealed a significant decrease, which agrees with the increased expression of the P-gp observed with the increase in g-levels, responsible for pumping this drug out. The neonatal Fc receptor-mediated transport of albumin-functionalized nanoparticles loaded with insulin showed no significant changes when increasing the g-levels. Thus, this study supports the effect of hypergravity on intestinal permeability is dependent on the molecule studied and the mechanism by which it is absorbed in the intestine.


Assuntos
Hipergravidade , Absorção Intestinal , Mucosa Intestinal/metabolismo , Administração Oral , Células CACO-2 , Camptotecina/administração & dosagem , Camptotecina/química , Camptotecina/farmacocinética , Dextranos/administração & dosagem , Dextranos/química , Dextranos/farmacocinética , Portadores de Fármacos/química , Impedância Elétrica , Fluoresceína-5-Isotiocianato/administração & dosagem , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/química , Fluoresceína-5-Isotiocianato/farmacocinética , Humanos , Insulina/administração & dosagem , Insulina/química , Insulina/farmacocinética , Micelas , Peso Molecular , Nanopartículas/química , Permeabilidade , Junções Íntimas/metabolismo
13.
Biophys J ; 120(5): 773-780, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33657362

RESUMO

Cells sense and react on changes of the mechanical properties of their environment and, likewise, respond to external mechanical stress applied to them. However, whether the gravitational field as overall body force modulates cellular behavior is unclear. Different studies demonstrated that micro- and hypergravity influences the shape and elasticity of cells, initiate cytoskeleton reorganization, and influence cell motility. All these cellular properties are interconnected and contribute to forces that cells apply on their surrounding microenvironment. Yet, studies that investigated changes of cell traction forces under hypergravity conditions are scarce. Here, we performed hypergravity experiments on 3T3 fibroblast cells using the large-diameter centrifuge at the European Space Agency - European Space Research and Technology Centre. Cells were exposed to hypergravity of up to 19.5 g for 16 h in both the upright and the inverted orientation with respect to the g-force vector. We observed a decrease in cellular traction forces when the gravitational field was increased up to 5.4 g, followed by an increase of traction forces for higher gravity fields up to 19.5 g independent of the orientation of the gravity vector. We attribute the switch in cellular response to shear thinning at low g-forces, followed by significant rearrangement and enforcement of the cytoskeleton at high g-forces.


Assuntos
Hipergravidade , Células 3T3 , Animais , Centrifugação , Fibroblastos , Camundongos , Tração
14.
Sci Rep ; 11(1): 2665, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514775

RESUMO

Many experiments have analyzed the effect of the space environment on various organisms. However, except for the group-rearing of mice in space, there has been little information on the behavior of organisms in response to gravity changes. In this study, we developed a simple Active Inactive Separation (AIS) method to extract activity and inactivity in videos obtained from the habitat cage unit of a space experiment. This method yields an activity ratio as a ratio of 'activity' within the whole. Adaptation to different gravitational conditions from 1g to hypergravity (HG) and from microgravity (MG) to artificial 1g (AG) was analyzed based on the amount of activity to calculate the activity ratio and the active interval. The result for the activity ratios for the ground control experiment using AIS were close to previous studies, so the effectiveness of this method was indicated. In the case of changes in gravity from 1g to HG, the ratio was low at the start of centrifugation, recovered sharply in the first week, and entered a stable period in another week. The trend in the AG and HG was the same; adapting to different gravity environments takes time.


Assuntos
Adaptação Fisiológica , Comportamento Animal , Hipergravidade , Ausência de Peso , Animais , Masculino , Camundongos
15.
Waste Manag ; 121: 412-421, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33445114

RESUMO

Municipal solid waste incineration fly ash (MSWI-FA) has been regulated as a hazardous waste that needs to treat with stabilization, solidification and landfill due to its amount of heavy metals, chlorides, sulfates and dioxin. While the proper treated MSWI-FA can be utilized as pozzolanic material to reduce the usage of Portland cement. The present article aims to develop an integrated wet-extraction and carbonation process for MSWI-FA stabilization, solidification and utilization via the high-gravity technology. A benchtop experiment demonstrated the dechlorination and CO2 sequestration of MSWI-FA and the carbonated product was applied as a supplementary cementitious material (SCM) in the cement mortar. Physical, chemical and thermal characteristics of raw, wet-extracted, and carbonated MSWI-FA were addressed in terms of the mean diameter, micropore area, micropore volume, chemical compositions, mineralogy and morphology. The effects of the liquid-to-solid ratio and high gravity factor were evaluated. Overall, a chloride extraction ratio of 36.35% and a CO2 capture capacity of 258.5 g-CO2 kg-FA-1 were achieved in the batch experiment. The results of water-energy consumption of chloride removal and CO2 fixation provided a novel insight into the future process criterion. In addition, the carbonated FA was found as binder to partially substitute Portland cement due to its large content of calcium carbonate. The workability and mechanical strength of cement mortar with partial substitution of stabilized FA were evaluated to determine the potential FA utilization pathway. Finally, the continuous process tests determined the key operation indexes for future process scale-up.


Assuntos
Hipergravidade , Metais Pesados , Eliminação de Resíduos , Carbono , Dióxido de Carbono , Cinza de Carvão , Incineração , Metais Pesados/análise , Material Particulado , Resíduos Sólidos/análise
16.
Cell Tissue Res ; 383(3): 1017-1024, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33159577

RESUMO

Although cardiac tissue is considered a target of gravitational force (g-force), the mechanism of hypergravity on the ion modulation or identification of ion transporters is still unknown. Thus, we determine the effect of hypergravity on a physical force-sensitive cytokine, IL-6 and its related channel activity to investigate rat cardiac function changes in response to accelerated g-force. Serum IL-6 levels and intracellular calcium levels of the right atrium were moderately increased under hypergravity stimulation (4g). IL-6 was involved in the modulation of sodium-potassium-chloride cotransporter (Nkcc) activity. Surprisingly, the right atrium under 4g revealed significantly enhanced Nkcc1 activity. The use of IL-6 on the NKCC1-overexpressed or native NKCC-expressing cells also showed enhanced NKCC1 activity. Hypergravity conditions were also involved in the oxidative stress activated Trpm2 channel and revealed an enhanced expression of the Trpm2 channel under 4g in the rat right atrium. In conclusion, hypergravity revealed that moderate increases in serum IL-6 and enhanced Nkcc1 activity was modulated by IL-6. In addition, enhanced Trpm2 channel expression could be involved in the increased intracellular calcium levels of the right atrium under hypergravitational force. We therefore address that enhanced physical force-sensitive cytokine and oxidative stress by the gravitational force mediate activation of the cotransporter involved in possibilities of edema and calcium loading in cardiac tissue.


Assuntos
Cálcio/metabolismo , Átrios do Coração/metabolismo , Hipergravidade , Interleucina-6/metabolismo , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Canalopatias/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
17.
Appl Biochem Biotechnol ; 193(3): 807-821, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33196971

RESUMO

Substantial progress has been made in ethanol fermentation technology under high gravity (HG) and very high gravity (VHG), which offer environmental and economic benefits. HG and VHG processes increase the productivity of ethanol, reduce distillation costs, and enable higher yields. The aim of the present study was to evaluate the use of sugarcane molasses as the medium component along with flocculating yeasts for fermentation in a fed-batch process employing this promising technology. We evaluated fed-batch fermentation, HG, and VHG involving a molasses-based medium with high concentrations of reducing sugars (209, 222, and 250 g/L). Fermentation of 222 g/L of total reducing sugars achieved 89.45% efficiency, with a final ethanol concentration of 104.4 g/L, whereas the highest productivity (2.98 g/(L.h)) was achieved with the fermentation of 209 g/L of total reducing sugars. The ethanol concentration achieved with the fermentation of 222 g/L of total reducing sugars was close to the value obtained for P'max (105.35 g/L). The kinetic model provided a good fit to the experimental data regarding the fermentation of 222 g/L. The results revealed that sugarcane molasses and flocculating yeasts can be efficiently used in HG fermentation to reduce the costs of the process and achieve high ethanol titers.


Assuntos
Reatores Biológicos , Hipergravidade , Modelos Biológicos , Melaço , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharum/química , Floculação , Cinética
18.
Sci Rep ; 10(1): 21214, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33273580

RESUMO

Biology is adapted to Earth's gravity force, and the long-term effects of varying gravity on the development of animals is unclear. Previously, we reported that high gravity, called hypergravity, increases defects in the development of motor neuron axons in the nematode Caenorhabditis elegans. Here, we show that a mutation in the unc-70 gene that encodes the cytoskeletal ß-spectrin protein suppresses hypergravity-induced axon defects. UNC-70 expression is required in both muscle and epidermis to promote the axon defects in high gravity. We reveal that the location of axon defects is correlated to the size of the muscle cell that the axon traverses. We also show that mutations that compromise key proteins of hemidesmosomal structures suppress hypergravity-induced axon defects. These hemidesmosomal structures play a crucial role in coupling mechanical force between the muscle, epidermis and the external cuticle. We speculate a model in which the rigid organization of muscle, epidermal and cuticular layers under high gravity pressure compresses the narrow axon migration pathways in the extracellular matrix hindering proper axon pathfinding of motor neurons.


Assuntos
Axônios , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Hipergravidade , Neurônios Motores/metabolismo , Espectrina/metabolismo , Animais , Animais Geneticamente Modificados , Proteínas de Caenorhabditis elegans/genética , Epiderme/metabolismo , Músculos/metabolismo , Espectrina/genética
19.
J Am Heart Assoc ; 9(24): e016479, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33283577

RESUMO

Background Hypergravity may promote human hemostasis thereby increasing thrombotic risk. Future touristic suborbital spaceflight will expose older individuals with chronic medical conditions, who are at much higher thromboembolic risk compared with professional astronauts, to hypergravity. Therefore, we tested the impact of hypergravity on hemostasis in healthy volunteers undergoing centrifugation. Methods and Results We studied 20 healthy seated men before and after 15 minutes under 3 Gz hypergravity on a long-arm centrifuge. We obtained blood samples for hemostasis testing before, immediately after, and 30 minutes after centrifugation. Tests included viscoelastic thromboelastometry, platelet impedance aggregometry, endothelial activation markers, blood rheology testing, microparticle analyses, and clotting factor analysis. Exposure to hypergravity reduced plasma volume by 12.5% (P=0.002) and increased the red blood cell aggregation index (P<0.05). With hypergravity, thrombelastographic clotting time of native blood shortened from 719±117 seconds to 628±89 seconds (P=0.038) and platetet reactivity increased (P=0.045). Hypergravity shortened partial thromboplastin time from 28 (26-29) seconds to 25 (24-28) seconds (P<0.001) and increased the activity of coagulation factors (eg, factor VIII 117 [93-134] versus 151 [133-175] %, P<0.001). Tissue factor concentration was 188±95 pg/mL before and 298±136 pg/mL after hypergravity exposure (P=0.023). Antithrombin (P=0.005), thrombin-antithrombin complex (P<0.001), plasmin-alpha2-antiplasmin complex (0.002), tissue-plasminogen activatior (P<0.001), and plasminogen activator inhibitor-1 (P=0.002) increased with centrifugation. Statistical adjustment for plasma volume attenuated changes in coagulation. Conclusions Hypergravity triggers low-level hemostasis activation through endothelial cell activation, increased viscoelasticity, and augmented platelet reactivity, albeit partly counteracted through endogenous coagulation inhibitors release. Hemoconcentration may contribute to the response.


Assuntos
Testes de Coagulação Sanguínea/métodos , Coagulação Sanguínea/fisiologia , Voluntários Saudáveis/estatística & dados numéricos , Hemostasia/fisiologia , Hipergravidade/efeitos adversos , Adulto , Astronautas/estatística & dados numéricos , Testes de Coagulação Sanguínea/estatística & dados numéricos , Células Endoteliais/fisiologia , Humanos , Masculino , Reologia/métodos , Medição de Risco , Voo Espacial/estatística & dados numéricos , Tromboelastografia/métodos , Trombose/sangue , Trombose/etiologia
20.
PLoS One ; 15(12): e0243098, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33296408

RESUMO

Insights into the effects of osteoarthritis (OA) and physical interventions on the musculoskeletal system are limited. Our goal was to analyze musculoskeletal changes in OA mice and test the efficacy of 8-week exposure to hypergravity, as a replacement of physical activity. 16-week-old male (C57BL/6J) mice allocated to sham control and OA groups not centrifuged (Ctrl 1g and OA 1g, respectively) or centrifuged at 2g acceleration (Ctrl 2g and OA 2g). OA 1g displayed decreased trabecular bone in the proximal tibia metaphysis and increased osteoclastic activity and local TNFα gene expression, all entirely prevented by 2g gravitational therapy. However, while cortical bone of tibia midshaft was preserved in OA 1g (vs. ctrl), it is thinner in OA 2g (vs. OA 1g). In the hind limb, OA at 1g increased fibers with lipid droplets by 48% in the tibialis anterior, a fact fully prevented by 2g. In Ctrl, 2g increased soleus, tibialis anterior and gastrocnemius masses. In the soleus of both Ctrl and OA, 2g induced larger fibers and a switch from type-II to type-I fiber. Catabolic (myostatin and its receptor activin RIIb and visfatine) and anabolic (FNDC5) genes dramatically increased in Ctrl 2g and OA 2g (p<0.01 vs 1g). Nevertheless, the overexpression of FNDC5 (and follistatine) was smaller in OA 2g than in Ctrl 2g. Thus, hypergravity in OA mice produced positive effects for trabecular bone and muscle typology, similar to resistance exercises, but negative effects for cortical bone.


Assuntos
Hipergravidade , Sistema Musculoesquelético/patologia , Osteoartrite do Joelho/terapia , Animais , Osso Esponjoso/patologia , Diáfises/patologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/patologia , Osteoartrite do Joelho/patologia , Tíbia/patologia
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