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We experimentally demonstrated the polarization change of femtosecond laser pulses in air by using electric-field-induced second-harmonic generation (E-FISHG) for the first time to our knowledge. The polarization change from linear to elliptical was observed at the laser intensity over the filamentation threshold. These results suggest that the polarization change can occur by the birefringence caused by filamentation. This phenomenon can be used for new applications such as an ultra-fast and precise three-dimensional electric field measurement by E-FISHG. In addition, E-FISHG can be an excellent tool to investigate the characteristics of femtosecond laser propagation such as filamentation.
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Fibrinogen Aα-chain amyloidosis is a hereditary systemic amyloidosis characterized by glomerular amyloid depositions, which are derived from the fibrinogen Aα-chain variant in humans. Despite its unique pathology, the pathogenic mechanisms of this disease are only partially understood. This is in part because comparative pathological studies on fibrinogen Aα-chain amyloidosis are currently unavailable as there is a lack of reported cases in animals other than humans. In this study, mass spectrometry-based proteomic analyses of Japanese squirrels (Sciurus lis) that died in five Japanese zoos showed that they developed glomerular-associated fibrinogen Aα-chain amyloidosis with an extremely high incidence rate (29/38 cases, 76.3%). The condition was found to be age-dependent in the Japanese squirrels, with 89% of individuals over 4 years of age affected. Mass spectrometry revealed that the C-terminal region of the fibrinogen Aα-chain was involved in amyloidogenesis in Japanese squirrels as well as humans. No gene variations were identified between amyloid-positive and amyloid-negative squirrels, which contrasted with the available data for humans. The results indicate that fibrinogen Aα-chain amyloidosis is a senile amyloidosis in Japanese squirrels. The results have also provided comparative pathological support that the amyloidogenic C-terminal region of the fibrinogen Aα-chain is involved in the characteristic glomerular pathology, regardless of the animal species. This study elucidates the potential causes of death in Japanese squirrels and will contribute to future comparative pathological studies of fibrinogen Aα-chain amyloidosis. © 2023 The Pathological Society of Great Britain and Ireland.
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Amiloidosis , Enfermedades Renales , Sciuridae , Animales , Amiloidosis/epidemiología , Amiloidosis/genética , Amiloidosis/veterinaria , Brotes de Enfermedades , Enfermedades Renales/genética , Enfermedades Renales/veterinaria , ProteómicaRESUMEN
Bone remodelling is mediated by orchestrated communication between osteoclasts and osteoblasts which, in part, is regulated by coupling and anti-coupling factors. Amongst formally known anti-coupling factors, Semaphorin 4D (Sema4D), produced by osteoclasts, plays a key role in downmodulating osteoblastogenesis. Sema4D is produced in both membrane-bound and soluble forms; however, the mechanism responsible for producing sSema4D from osteoclasts is unknown. Sema4D, TACE and MT1-MMP are all expressed on the surface of RANKL-primed osteoclast precursors. However, only Sema4D and TACE were colocalized, not Sema4D and MT1-MMP. When TACE and MT1-MMP were either chemically inhibited or suppressed by siRNA, TACE was found to be more engaged in shedding Sema4D. Anti-TACE-mAb inhibited sSema4D release from osteoclast precursors by ~90%. Supernatant collected from osteoclast precursors (OC-sup) suppressed osteoblastogenesis from MC3T3-E1 cells, as measured by alkaline phosphatase activity, but OC-sup harvested from the osteoclast precursors treated with anti-TACE-mAb restored osteoblastogenesis activity in a manner that compensates for diminished sSema4D. Finally, systemic administration of anti-TACE-mAb downregulated the generation of sSema4D in the mouse model of critical-sized bone defect, whereas local injection of recombinant sSema4D to anti-TACE-mAb-treated defect upregulated local osteoblastogenesis. Therefore, a novel pathway is proposed whereby TACE-mediated shedding of Sema4D expressed on the osteoclast precursors generates functionally active sSema4D to suppress osteoblastogenesis.
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Osteoclastos , Semaforinas , Animales , Ratones , Modelos Animales de Enfermedad , Metaloproteinasa 14 de la Matriz/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Semaforinas/genética , Semaforinas/metabolismoRESUMEN
The adhesion mechanism of epoxy resin to the γ-alumina (110) surface was investigated using first-principles density functional theory (DFT). Aluminum materials are lightweight and are used in a wide range of industrial fields. Its surface is oxidized to alumina, and the stable surface is known as the γ-alumina (110) surface. The coverage of hydroxy groups by chemisorbed water molecules on this surface varied depending on the pretreatment temperature. In this study, we investigated the adhesive interactions of epoxy resin on four alumina surfaces with different densities of surface hydroxy groups (0, 3, 6, and 9 OH/nm2) and have discussed their effects. At each interface, the energy curves of the vertically displaced epoxy resin were calculated and the adhesive forces were estimated by differentiating these curves. As the coverage of the surface hydroxy groups increased from 0 to 6 OH/nm2, the adhesive strength gradually decreased. However, the adhesive strength at 9 OH/nm2 was relatively large and almost equal to that at 3 OH/nm2. This inverse volcano-type behavior was analyzed via the decomposition of adhesive forces and the crystal orbital Hamilton population (COHP). The decomposition of adhesive forces into DFT and dispersion components revealed that the inverse volcano-type behavior is derived from the DFT component, and the interfacial interactions owing to the DFT component are accompanied by charge transfer. These were investigated using a COHP analysis, which revealed that this behavior was caused by changes in the activity of the aluminum atoms on the surface and surface reconstruction by chemisorbed water molecules. It is noteworthy that the adhesive strength for 9 OH/nm2 was only 6.9% lower than that for 0 OH/nm2 wherein the chemisorbed water molecules were completely removed from the surface. These results are expected to provide a guideline for the adhesion of epoxy resin to aluminum materials.
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BACKGROUND: A rhesus macaque with the fourth highest plasma cholesterol (CH) levels of 501 breeding macaques was identified 22 years ago. Seven offspring with gene mutations causing hypercholesterolemia were obtained. METHODS: Activity of low-density lipoprotein receptor (LDLR), plasma CH levels and mRNA expression levels of LDLR were measured after administration of 0.1% (0.27 mg/kcal) or 0.3% CH. RESULTS: Activity of p. (Cys82Tyr) of LDLR was 71% and 42% in the heterozygotes and a homozygote, respectively. The mRNA expression level of LDLR in the p. (Val241Ile) of membrane-bound transcription factor protease, site 2 (MBTPS2, S2P protein) was 0.83 times lower than normal levels. LDLR mRNA levels were increased for up to 4 weeks by administration of 0.3% CH before suddenly decreasing to 80% of the baseline levels after 6 weeks. CONCLUSION: Oligogenic mutations of p. (Cys82Tyr) in LDLR and p. (Val241Ile) in MBTPS2 (S2P) caused hypercholesterolemia exceeding cardiovascular risk levels under a 0.1% CH diet.
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Hipercolesterolemia , Animales , Hipercolesterolemia/genética , Macaca mulatta/genética , Mutación , ARN MensajeroRESUMEN
Adenovirus (Ad) vector-mediated transduction can cause hepatotoxicity during two phases, at â¼2 and 10 days after administration. Early hepatotoxicity is considered to involve inflammatory cytokines; however, the precise mechanism remains to be clarified. We examined the mechanism of early Ad vector-induced hepatotoxicity by using a conventional Ad vector, Ad-CAL2, and a modified Ad vector, Ad-E4-122aT-CAL2. Ad-E4-122aT-CAL2 harbors sequences complementary to the liver-specific miR-122a in the 3' untranslated region of E4, leading to significant suppression of leaky Ad gene expression in the liver via posttranscriptional gene silencing and a significant reduction in late-phase hepatotoxicity. We found that Ad-E4-122aT-CAL2 transduction significantly attenuated acute hepatotoxicity, although Ad-E4-122aT-CAL2 and Ad-CAL2 induced comparable cytokine expression levels in the liver and spleen. IL-6, a major inflammatory cytokine induced by Ad vectors, significantly enhanced leaky Ad gene expression and cytotoxicity in primary mouse hepatocytes following Ad-CAL2 but not Ad-E4-122aT-CAL2 transduction. Furthermore, leaky Ad gene expression and cytotoxicity in Ad-CAL2-treated hepatocytes in the presence of IL-6 were significantly suppressed upon inhibition of JAK and STAT3. Ad vector-mediated acute hepatotoxicities and leaky Ad expression were significantly reduced in IL-6 knockout mice compared with those in wild-type mice. Thus, Ad vector-induced IL-6 promotes leaky Ad gene expression, leading to acute hepatotoxicity.
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Infecciones por Adenoviridae/inmunología , Adenoviridae/fisiología , Vectores Genéticos/genética , Hepatocitos/fisiología , Inflamación/inmunología , Interleucina-6/metabolismo , Hepatopatías/genética , Animales , Células Cultivadas , Citocinas/metabolismo , Regulación de la Expresión Génica , Hepatocitos/virología , Interleucina-6/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Virales/genética , Proteínas Virales/metabolismoRESUMEN
Psychosocial stress precipitates mental illnesses, such as depression, and increases the risk of other health problems, including cardiovascular diseases. In this study, we observed the effects of psychosocial stress on the histopathological features of systemic organs and tissues in a mouse psychosocial stress model, namely the subchronic and mild social defeat stress (sCSDS) model. There were several pathological findings in the tissues of both sCSDS and control mice. Mild fibrosis of the heart was observed in sCSDS mice but not in control mice. Extramedullary hematopoiesis in the spleen and hemorrhage in the lungs were observed in both the control and sCSDS mice. Focal necrosis of the liver was seen only in control mice. Furthermore, putrefactive substances in the blood plasma were analyzed because these metabolites originating from intestinal fermentation might be linked to heart fibrosis. Among them, plasma p-cresyl glucuronide and p-cresyl sulfate concentrations significantly increased owing to subchronic social defeat stress, which might influence cardiac fibrosis in sCSDS mice. In conclusion, several pathological features such as increased cardiac fibrosis and elevated plasma putrefactive substances were found in sCSDS mice. Thus, sCSDS mice are a potential model for elucidating the pathophysiology of psychosocial stress and heart failure.
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Plasma , Derrota Social , Ratones , Masculino , Animales , Ratones Endogámicos C57BL , Fibrosis , Estrés Psicológico/metabolismoRESUMEN
Carnitine deficiency and impaired glucose tolerance (IGT) exacerbate liver steatosis. Given the current lack of ideal murine nonalcoholic steatohepatitis (NASH) models, we investigated new NASH models using jvs/+ mice with low carnitine and wild-type mice with low-dose alloxan-induced IGT. The jvs/+ and wild-type mice were divided into jvs/+ mice fed a high-fat diet (HFD) from 3 weeks of age (HF hetero group), wild-type mice with low-dose alloxan treatment fed HFD (AL + HF wild group), wild-type mice fed HFD (HF wild group), and two types of mice fed a normal diet-jvs/+ and wild-type (intact group). All mice were sacrificed at 20 or 40 weeks of age. All male HFD-fed mice showed obesity, IGT, high blood insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), high liver enzyme levels, and high cholesterol levels. The degree of IGT was the worst in the AL + HF wild group, and blood insulin levels and HOMA-IR score were remarkably increased from 20 to 40 weeks of age. Almost all HFD-fed mice showed steatosis, fibrosis, and lobular inflammation in the centrilobular zone. These changes were accompanied by hepatocyte ballooning and were enhanced at 40 weeks of age. Furthermore, the incidence rate of nodular hyperplasia and adenoma in both the HF hetero and AL + HF wild groups was nearly 30%. We successfully established two novel murine models of NASH using male jvs/+ mice with low carnitine and male wild-type mice with IGT that eventually developed obesity, fatty liver, insulin resistance, liver fibrosis, and tumorigenesis. These results suggest that low carnitine levels and early-stage induction of IGT are important factors in the progression of NASH to tumorigenesis, similar to human NASH.
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Intolerancia a la Glucosa , Resistencia a la Insulina , Insulinas , Enfermedad del Hígado Graso no Alcohólico , Aloxano/efectos adversos , Animales , Carcinogénesis , Carnitina , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Intolerancia a la Glucosa/etiología , Hígado , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Obesidad/complicacionesRESUMEN
To ensure the quality and reliability of products bonded by epoxy resin adhesives, elucidation of the microscopic adhesion mechanism is essential. The adhesive interaction and bonding strength between epoxy resins and hydroxylated γ-alumina (001) surfaces were investigated by using a combined molecular dynamics (MD) and density functional theory (DFT) study. The curing reaction of an epoxy resin consisting of diglycidyl ether of bisphenol A (DGEBA) and 4,4'-diaminodiphenyl sulfone (DDS) was simulated. The resin structure was divided into fragmentary structures to study the interaction of each functional group with the alumina surface using DFT calculations. From the characteristics of the adhesive structures and the calculated adhesion energies, it was found that the fragments forming hydrogen bonds with hydroxy groups on the alumina surface resulted in large adhesion energies. On the other hand, the fragments adsorbed on the alumina surface via dispersion interactions resulted in small adhesion energies. The adhesion forces evaluated from the Hellmann-Feynman force calculations indicated the significant contribution of the hydroxy groups and benzene ether moieties derived from DGEBA to the adhesive stress of the DGEBA/DDS epoxy resin. The direction of hydrogen bonding between the epoxy resin and the surface and the difference in geometry at the interface between the donor and acceptor of hydrogen bonding played a central role in maintaining the adhesive strength during the failure process of the adhesive interface.
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Identification of early biomarkers of stress is important for preventing mood and anxiety disorders. Saliva is an easy-to-collect and non-invasive diagnostic target. The aim of this study was to characterize the changes in salivary whole microRNAs (miRNAs) and metabolites in mice subjected to subchronic and mild social defeat stress (sCSDS). In this study, we identified seven upregulated and one downregulated miRNAs/PIWI-interacting RNA (piRNA) in the saliva of sCSDS mice. One of them, miR-208b-3p, which is reported as a reliable marker for myocardial infarction, was upregulated in the saliva of sCSDS mice. Histological analysis showed frequent myocardial interstitial fibrosis in the heart of such mice. In addition, gene ontology and pathway analyses suggested that the pathways related to energy metabolism, such as the oxidative phosphorylation and the pentose phosphate pathway, were significantly related to the miRNAs affected by sCSDS in saliva. In contrast, salivary metabolites were not significantly changed in the sCSDS mice, which is consistent with our previous metabolomic study on the plasma of sCSDS mice. Taken in the light of previous studies, the present study provides novel potential stress biomarkers for future diagnosis using saliva.
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MicroARNs , Derrota Social , Ratones , Animales , MicroARNs/genética , MicroARNs/metabolismo , Ratones Endogámicos C57BL , Estrés Psicológico/genética , Estrés Psicológico/metabolismo , Metaboloma , Modelos Animales de Enfermedad , Biomarcadores/metabolismoRESUMEN
Effects of the antiosteoblastogenesis factor Semaphorin 4D (Sema4D), expressed by thrombin-activated platelets (TPs), on osteoblastogenesis, as well as osteoclastogenesis, were investigated in vitro. Intact platelets released both Sema4D and IGF-1. However, in response to stimulation with thrombin, platelets upregulated the release of Sema4D, but not IGF-1. Anti-Sema4D-neutralizing monoclonal antibody (mAb) upregulated TP-mediated osteoblastogenesis in MC3T3-E1 osteoblast precursors. MC3T3-E1 cells exposed to TPs induced phosphorylation of Akt and ERK further upregulated by the addition of anti-sema4D-mAb, suggesting the suppressive effects of TP-expressing Sema4D on osteoblastogenesis. On the other hand, TPs promoted RANKL-mediated osteoclastogenesis in the primary culture of bone-marrow-derived mononuclear cells (BMMCs). Among the known three receptors of Sema4D, including Plexin B1, Plexin B2 and CD72, little Plexin B2 was detected, and no Plexin B1 was detected, but a high level of CD72 mRNA was detected in RANKL-stimulated BMMCs by qPCR. Both anti-Sema4D-mAb and anti-CD72-mAb suppressed RANKL-induced osteoclast formation and bone resorptive activity, suggesting that Sema4D released by TPs promotes osteoclastogenesis via ligation to a CD72 receptor. This study demonstrated that Sema4D released by TPs suppresses osteogenic activity and promotes osteoclastogenesis, suggesting the novel property of platelets in bone-remodeling processes.
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Osteogénesis , Semaforinas , Antígenos CD , Plaquetas , Proteínas del Tejido Nervioso/genética , Receptores de Superficie Celular/genética , Semaforinas/genética , Semaforinas/farmacología , Trombina/farmacologíaRESUMEN
It is well known that Semaphorin 4D (Sema4D) inhibits IGF-1-mediated osteogenesis by binding with PlexinB1 expressed on osteoblasts. However, its elevated level in the gingival crevice fluid of periodontitis patients and the broader scope of its activities in the context of potential upregulation of osteoclast-mediated periodontal bone-resorption suggest the need for further investigation of this multifaceted molecule. In short, the pathophysiological role of Sema4D in periodontitis requires further study. Accordingly, attachment of the ligature to the maxillary molar of mice for 7 days induced alveolar bone-resorption accompanied by locally elevated, soluble Sema4D (sSema4D), TNF-α and RANKL. Removal of the ligature induced spontaneous bone regeneration during the following 14 days, which was significantly promoted by anti-Sema4D-mAb administration. Anti-Sema4D-mAb was also suppressed in vitro osteoclastogenesis and pit formation by RANKL-stimulated BMMCs. While anti-Sema4D-mAb downmodulated the bone-resorption induced in mouse periodontitis, it neither affected local production of TNF-α and RANKL nor systemic skeletal bone remodeling. RANKL-induced osteoclastogenesis and resorptive activity were also suppressed by blocking of CD72, but not Plexin B2, suggesting that sSema4D released by osteoclasts promotes osteoclastogenesis via ligation to CD72 receptor. Overall, our data indicated that ssSema4D released by osteoclasts may play a dual function by decreasing bone formation, while upregulating bone-resorption.
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Pérdida de Hueso Alveolar , Periodontitis , Pérdida de Hueso Alveolar/etiología , Animales , Antígenos CD , Regeneración Ósea , Modelos Animales de Enfermedad , Ratones , Periodontitis/patología , Semaforinas , Factor de Necrosis Tumoral alfaRESUMEN
We investigated the performance of electric-field-induced second-harmonic generation (E-FISHG) by spectroscopic measurement using high-intensity femtosecond laser pulses. The second-harmonic intensity increased quadratically versus the applied electric field, as expected from the theory, up to 15 kV/cm with the laser energy up to 2.5 mJ, which is â¼5 times higher than the observable optical breakdown threshold. In addition, when the laser energy was 2.8 mJ, â¼80 times signal intensity at 0.23 mJ was obtained. These results suggest that the electric-field measurement by E-FISHG with high-intensity second harmonics is expected by using high-intensity laser pulses above the observable optical breakdown threshold. Spectroscopic measurement shows no E-FISHG of white light generated by self-phase modulation in laser-induced filament.
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The presence of adsorbed water on hydrophilic solid surfaces should be taken into account, especially in humid environments. It significantly reduces the adhesive strength between the epoxy resin and the adherend surface. Here, the adhesion structure of interfacial water sandwiched between bisphenol A epoxy resin and a hydroxylated silica (001) surface is investigated with microsecond molecular dynamics simulations. Specifically, interfacial water layers with initial thicknesses of 7.5, 10, and 20 Å are modeled. The density curves of water and the diglycidyl ether of bisphenol A show that at room temperature, the surface of the silica with hydroxyl groups is completely covered with a thick layer of water. For water layers thinner than 10 Å, the density of epoxy resin on the silica surface increases when the system is heated and does not return to the original density when the system is cooled. Furthermore, calculation of the interaction energy revealed that the exclusion of water from the hydroxylated surface by epoxy resin during heating can contribute to the increase in the adhesive interaction between the epoxy resin and the silica surface with hydroxyl groups.
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To induce and maintain naïve pluripotency in mouse embryonic and induced pluripotent stem cells (ESCs/iPSCs), chemically defined N2B27 medium with PD0325901, CHIR99021, and leukemia inhibitory factor (2i/LIF) is a classic and simple condition. However, this method cannot be simply extrapolated to human ESCs/iPSCs that are principally stabilized in primed pluripotency and become primitive neuroepithelium-like cells in N2B27+2i/LIF culture. Here, we assessed iPSC reprogramming of fibroblasts from chimpanzee, our closest living relative, in N2B27+2i/LIF culture. Under this condition, chimpanzee cells formed alkaline phosphatase-positive dome-shaped colonies. The colony-forming cells could be stably expanded by serial passaging without a ROCK inhibitor. However, their gene expression was distinct from iPSCs and neuroepithelium. They expressed the OCT3/4 transgene and a subset of transcripts associated with pluripotency, mesenchymal-epithelial transition, and neural crest formation. These cells exhibited a differentiation potential into the three germ layers in vivo and in vitro. The current study demonstrated that iPSC reprogramming in N2B27+2i/LIF culture converted chimpanzee fibroblasts into a multipotent cancerous state with unique gene expression, but not fully pluripotent stem cells.
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Diferenciación Celular/genética , Reprogramación Celular/genética , Células Madre Pluripotentes Inducidas/citología , Células Madre Multipotentes/citología , Animales , Benzamidas/farmacología , Diferenciación Celular/efectos de los fármacos , Reprogramación Celular/efectos de los fármacos , Difenilamina/análogos & derivados , Difenilamina/farmacología , Transición Epitelial-Mesenquimal/genética , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Estratos Germinativos/efectos de los fármacos , Estratos Germinativos/crecimiento & desarrollo , Humanos , Factor Inhibidor de Leucemia/farmacología , Ratones , Células Madre Multipotentes/efectos de los fármacos , Cresta Neural/citología , Pan troglodytes , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/efectos de los fármacos , Piridinas/farmacología , Pirimidinas/farmacologíaRESUMEN
MRI has become an invaluable diagnostic tool in all areas of the body. However, it has not been widely used to image odontogenic tumors of the jaw. Major advantages of MRI include excellent soft tissue contrast in the absence of ionizing radiation. Furthermore, diffusion-weighted MRI and dynamic contrast-enhanced MRI can be used as functional imaging techniques for assessing tissue biology. In this review article, we present representative MR images of several types of odontogenic tumors, and discuss MR imaging characteristics useful for differential diagnosis.
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Tumores Odontogénicos , Diagnóstico Diferencial , Imagen de Difusión por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética , Tumores Odontogénicos/diagnóstico por imagenRESUMEN
BACKGROUND: Periodontopathic bacteria such as Porphyromonas gingivalis produce several metabolites, including lipopolysaccharide (LPS) and n-butyric acid (BA). Past work suggested that periodontal infection may cause cognitive impairment in mice. AIMS: To elucidate the mechanisms by which metabolites such as LPS and BA, resulting from Porphyromonas gingivalis activity, induce immunological and physiological abnormalities in mice. METHODS: In the present work, 28 male ICR mice were placed in an open-field arena and the total distance (cm/600 s) they covered was recorded. Based on their moving distances, mice were divided into 4 groups (n = 7) and injected the following substances into their gingival tissues for 32 consecutive days: saline (C), 5 mmol/L of BA (B), 1 µg/mouse of LPS (L), and BA-LPS (BL) solutions. Distances covered by mice were also measured on days 14 and 21, with their habituation scores considered as "(moving distance on day 14 or 21)/(moving distance on day 0)". Afterwards, mice were dissected, and hippocampal gene expression and the concentrations of short-chain fatty acids, neurotransmitters and cytokines in their blood plasma and brains were analyzed. In addition, mouse brain and liver tissues were fixed and visually assessed for histopathological abnormalities. RESULTS: Group BL had significantly higher habituation scores than C and B on day 14. LPS induced higher habituation scores on day 21. LPS induced significant decreases in the mRNA levels of interleukin (IL)-6 and brain-derived neurotrophic factors, and an increase in neurotrophic tyrosine kinase receptor type 2. In both plasma and brain, LPS induced a significant acetate increase. Moreover, LPS significantly increased acetylcholine in brain. In plasma alone, LPS and BA significantly decreased monocyte chemoattractant protein 1 (MCP-1). However, while LPS significantly decreased tyrosine, BA significantly increased it. Lastly, LPS significantly decreased IL-6 and tumor necrosis factor in plasma. No histopathological abnormalities were detected in liver or brain tissues of mice. CONCLUSION: We showed that injections of LPS and/or BA induced mice to move seemingly tireless and that both LPS and BA injections strongly induced a reduction of MCP-1 in blood plasma. We concluded that LPS and BA may have been crucial to induce and/or aggravate abnormal behavior in mice.
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Conducta Animal/efectos de los fármacos , Ácido Butírico/administración & dosificación , Citocinas/metabolismo , Encía/efectos de los fármacos , Hipocampo/efectos de los fármacos , Lipopolisacáridos/administración & dosificación , Animales , Ácidos Grasos Volátiles/metabolismo , Encía/metabolismo , Enfermedades de las Encías/metabolismo , Hipocampo/metabolismo , MasculinoRESUMEN
We discover a new tricritical point realized only in nonequilibrium steady states, using the AdS/CFT correspondence. Our system is a (3+1)-dimensional strongly coupled large-N_{c} gauge theory. The tricritical point is associated with a chiral symmetry breaking under the presence of an electric current and a magnetic field. The critical exponents agree with those of the Landau theory of equilibrium phase transitions. This suggests that the presence of a Landau-like phenomenological theory behind our nonequilibrium phase transitions.
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Photosynthetic water oxidation takes place through the light-driven cycle of five intermediates (S0-S4) of the water oxidizing complex (WOC), which consists of the Mn4CaO5 cluster and surrounding amino acid residues in photosystem II. Clarifying the protonation structures of the Mn4CaO5 cluster and its water ligands (W1-W4) is essential for understanding the molecular mechanism of water oxidation. Here, we performed normal mode analysis of WOC in the S0 and S1 states using quantum mechanics/molecular mechanics calculations and simulated an S1-minus-S0 infrared difference spectrum focusing on the symmetric COO- stretching (νsCOO-) region. The calculated spectrum by an S0 model, in which O4 of the Mn4CaO5 cluster is protonated and W2 is H2O, and a corresponding S1 state with deprotonated O4 best reproduced the νsCOO- features of the experimental spectrum, whereas models with protonated O5 showed poor agreement. In addition, comparison of the calculated coordination distances of the water ligands with the experimental data by X-ray diffraction analysis indicates that W2 is most probably not OH- but H2O both in the S0 and S1 states. The present calculations thus strongly suggest that the S0 state has a protonation structure of O4-H and W2 = H2O. The O4-H structure in the S0 state supports the view that this proton is released through the O4-water chain immediately after electron transfer during the S0â S1 transition.
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Modelos Moleculares , Complejo de Proteína del Fotosistema II/química , Agua/química , Oxidación-Reducción , Protones , Teoría CuánticaRESUMEN
Photosynthetic water oxidation is catalyzed by the Mn4Ca cluster in photosystem II (PSII). The nearby redox-active tyrosine (YZ) serves as a direct electron acceptor of the Mn4Ca cluster and it forms a low-barrier H-bond (LBHB) with a neighboring histidine residue (D1-His190). Experimental evidence indicates that YZ oxidation triggers changes in the hydrogen bonding network that precede proton abstraction from the Mn4Ca cluster. In order to characterize such changes, we compare ab initio molecular dynamics simulations of different states of the catalytic cycle of PSII with dynamics of isolated tyrosine models (namely, p-cresol) in different oxidation states. The systematic comparison of the H-bond networks in different simulated systems suggests that the YZ oxidation leads to a water hydration pattern which is more similar to that of the neutral p-cresol rather than that of the p-cresol anion. Our simulations also reveal the twofold nature of the interactions between YZ and the Mn4Ca cluster. Firstly, the YZ oxidation triggers rapid structural changes of the H-bond pattern in the proximity of the cluster which have been observed to propagate on the ps time scale on the Ca2+ hydration shell up to other water molecules in the proximity of the cluster. Secondly, it is clear that YZ interacts with the Mn4Ca cluster also through Coulombic interactions mediated by CP43-Arg357 through the remaining positive charge of the pair. Our results are able to identify, for the first time, the structural rearrangements guided by the oxidation of YZ necessary for the evolution of the water splitting reaction in PSII. Based on these findings, we propose a mechanism of structural changes which is functional towards the progression of the catalytic cycle in PSII.