RESUMO
Continuous formation of somatic tissues in plants requires functional stem cell niches where undifferentiated cells are maintained. In Arabidopsis thaliana, PLETHORA (PLT) and SCARECROW (SCR) genes are outputs of apical-basal and radial patterning systems, and both are required for root stem cell specification and maintenance. The WUSCHEL-RELATED HOMEOBOX 5 (WOX5) gene is specifically expressed in and required for functions of a small group of root stem cell organizer cells, also called the quiescent center (QC). PLT and SCR are required for QC function, and their expression overlaps in the QC; however, how they specify the organizer has remained unknown. We show that PLT and SCR genetically and physically interact with plant-specific teosinte-branched cycloidea PCNA (TCP) transcription factors to specify the stem cell niche during embryogenesis and maintain organizer cells post-embryonically. PLT-TCP-SCR complexes converge on PLT-binding sites in the WOX5 promoter to induce expression.
Assuntos
Proteínas de Arabidopsis/metabolismo , Raízes de Plantas/genética , Nicho de Células-Tronco , Fatores de Transcrição/metabolismo , Arabidopsis/citologia , Arabidopsis/embriologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Mutação , Raízes de Plantas/citologia , Raízes de Plantas/embriologia , Raízes de Plantas/crescimento & desenvolvimento , Domínios e Motivos de Interação entre Proteínas , Fatores de Transcrição/química , Fatores de Transcrição/genéticaRESUMO
Diabetes causes a range of complications that can affect multiple organs. Hyperglycemia is an important driver of diabetes-associated complications, mediated by biological processes such as dysfunction of endothelial cells, fibrosis, and alterations in leukocyte number and function. Here, we dissected the transcriptional response of key cell types to hyperglycemia across multiple tissues using single-cell RNA sequencing (scRNA-seq) and identified conserved, as well as organ-specific, changes associated with diabetes complications. By studying an early time point of diabetes, we focus on biological processes involved in the initiation of the disease, before the later organ-specific manifestations had supervened. We used a mouse model of type 1 diabetes and performed scRNA-seq on cells isolated from the heart, kidney, liver, and spleen of streptozotocin-treated and control male mice after 8 weeks and assessed differences in cell abundance, gene expression, pathway activation, and cell signaling across organs and within organs. In response to hyperglycemia, endothelial cells, macrophages, and monocytes displayed organ-specific transcriptional responses, whereas fibroblasts showed similar responses across organs, exhibiting altered metabolic gene expression and increased myeloid-like fibroblasts. Furthermore, we found evidence of endothelial dysfunction in the kidney, and of endothelial-to-mesenchymal transition in streptozotocin-treated mouse organs. In summary, our study represents the first single-cell and multi-organ analysis of early dysfunction in type 1 diabetes-associated hyperglycemia, and our large-scale dataset (comprising 67 611 cells) will serve as a starting point, reference atlas, and resource for further investigating the events leading to early diabetic disease.
Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Camundongos , Animais , Masculino , Diabetes Mellitus Tipo 1/genética , Células Endoteliais , Estreptozocina/toxicidade , Camundongos Endogâmicos C57BL , Hiperglicemia/genética , Análise de Sequência de RNARESUMO
Finasteride is used in female-pattern hair loss, hirsutism, and polycystic ovarian syndrome. It inhibits 5α-reductase, which is an important enzyme in the biosynthesis of neurosteroids. The effects of finasteride treatment on mental health in female patients as well as the effects of repeated/chronic finasteride administration in female rodents are still unknown. Accordingly, in our study, we administered finasteride (10, 30, or 100 mg/Kg, s.c.) for 6 days in female rats and evaluated behavior, plasma steroid levels, and synaptic plasticity. Depression-like behavior was evaluated using forced swim test (FST) and splash test. Anxiety-like behavior was evaluated using novelty-suppressed feeding task (NSFT), elevated plus maze (EPM), open field test (OFT), and light-dark test (LDT). Plasma steroid levels were assessed using ELISA and synaptic plasticity by field potential recordings. We observed that finasteride decreased total immobility duration in FST, indicating antidepressant-like effect and decreased the latency to first bite in NSFT, showing anxiolytic-like effect. We also found a significant increase in plasma estradiol and a significant decrease in plasma corticosterone level. Furthermore, field potential recordings showed that finasteride increased hippocampal long-term potentiation. These results indicate that repeated finasteride administration in female rats may have antidepressant- and anxiolytic-like effect, which might be mediated by enhanced estradiol levels or decreased corticosterone levels. Further studies are required to validate the molecular mechanisms underlying the effects of finasteride in female rats. Understanding the mechanisms will help us in developing novel neurosteroid-based therapeutics in the treatment of neuropsychiatric disorders in women.
Assuntos
Ansiolíticos , Finasterida , Humanos , Ratos , Feminino , Animais , Finasterida/efeitos adversos , Ansiolíticos/farmacologia , Corticosterona , Depressão/tratamento farmacológico , Esteroides , Estradiol , Antidepressivos/farmacologia , Plasticidade NeuronalRESUMO
The master control of mammalian circadian rhythms is the suprachiasmatic nucleus (SCN), which is formed by the ventral and dorsal regions. In SCN neurons, GABA has an important function and even excitatory actions in adulthood. However, the physiological role of this neurotransmitter in the developing SCN is unknown. Here, we recorded GABAergic postsynaptic currents (in the perforated-patch configuration using gramicidin) to determine the chloride reversal potential (ECl) and also assessed the immunological expression of the Na-K-Cl cotransporter 1 (NKCC1) at early ages of the rat (postnatal days (P) 3 to 25), during the day and night, in the two SCN regions. We detected that ECl greatly varied with age and depending on the SCN region and time of day. Broadly speaking, ECl was more hyperpolarized with age, except for the oldest age studied (P20-25) in both day and night in the ventral SCN, where it was less negative. Likewise, ECl was more hyperpolarized in the dorsal SCN both during the day and at night; while ECl was more negative at night both in the ventral and the dorsal SCN. Moreover, the total NKCC1 fluorescent expression was higher during the day than at night. These results imply that NKCC1 regulates the circadian and developmental fluctuations in the [Cl-]i to fine-tune ECl, which is crucial for either excitatory or inhibitory GABAergic actions to occur in the SCN.
Assuntos
Cloretos , Ritmo Circadiano , Membro 2 da Família 12 de Carreador de Soluto , Núcleo Supraquiasmático , Animais , Núcleo Supraquiasmático/metabolismo , Ritmo Circadiano/fisiologia , Ratos , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Masculino , Cloretos/metabolismo , Ácido gama-Aminobutírico/metabolismo , Ratos Wistar , Técnicas de Patch-Clamp , Envelhecimento/fisiologiaRESUMO
Circadian rhythms synchronize to light through the retinohypothalamic tract (RHT), which is a bundle of axons coming from melanopsin retinal ganglion cells, whose synaptic terminals release glutamate to the ventral suprachiasmatic nucleus (SCN). Activation of AMPA-kainate and NMDA postsynaptic receptors elicits the increase in intracellular calcium required for triggering the signaling cascade that ends in phase shifts. During aging, there is a decline in the synchronization of circadian rhythms to light. With electrophysiological (whole-cell patch-clamp) and immunohistochemical assays, in this work, we studied pre- and postsynaptic properties between the RHT and ventral SCN neurons in young adult (P90-120) and old (P540-650) C57BL/6J mice. Incremental stimulation intensities (applied on the optic chiasm) induced much lesser AMPA-kainate postsynaptic responses in old animals, implying a lower recruitment of RHT fibers. Conversely, a higher proportion of old SCN neurons exhibited synaptic facilitation, and variance-mean analysis indicated an increase in the probability of release in RHT terminals. Moreover, both spontaneous and miniature postsynaptic events displayed larger amplitudes in neurons from aged mice, whereas analysis of the NMDA and AMPA-kainate components (evoked by RHT electrical stimulation) disclosed no difference between the two ages studied. Immunohistochemistry revealed a bigger size in the puncta of vGluT2, GluN2B, and GluN2A of elderly animals, and the number of immunopositive particles was increased, but that of PSD-95 was reduced. All these synaptic adaptations could be part of compensatory mechanisms in the glutamatergic signaling to ameliorate the loss of RHT terminals in old animals.
Assuntos
Envelhecimento , Ácido Glutâmico , Camundongos Endogâmicos C57BL , Núcleo Supraquiasmático , Transmissão Sináptica , Animais , Camundongos , Núcleo Supraquiasmático/fisiologia , Núcleo Supraquiasmático/metabolismo , Transmissão Sináptica/fisiologia , Envelhecimento/fisiologia , Ácido Glutâmico/metabolismo , Masculino , Potenciais Pós-Sinápticos Excitadores/fisiologia , Vias Visuais/fisiologia , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Técnicas de Patch-Clamp , Receptores de N-Metil-D-Aspartato/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismoRESUMO
This study aimed to evaluate the effects of inhibitors of the fractalkine pathway in hyperalgesia in inflammatory and neuropathic orofacial pain in male rats and the morphological changes in microglia and satellite glial cells (SGCs). Rats were submitted to zymosan-induced arthritis of the temporomandibular joint or infraorbital nerve constriction, and treated intrathecally with a P2 X7 antagonist, a cathepsin S inhibitor or a p-38 mitogen-activated protein kinase (MAPK) inhibitor. Mechanical hyperalgesia was evaluated 4 and 6 h following arthritis induction or 7 and 14 days following nerve ligation. The expression of the receptor CX3 CR1 , phospho-p-38 MAPK, ionized calcium-binding adapter molecule-1 (Iba-1), and glutamine synthetase and the morphological changes in microglia and SGCs were evaluated by confocal microscopy. In both inflammatory and neuropathic models, untreated animals presented a higher expression of CX3 CR1 and developed hyperalgesia and up-regulation of phospho-p-38 MAPK, which was prevented by all drugs (p < .05). The number of microglial processes endpoints and the total branch length were lower in the untreated animals, but the overall immunolabeling of Iba-1 was altered only in neuropathic rats (p < .05). The mean area of SGCs per neuron was significantly altered only in the inflammatory model (p < .05). All morphological alterations were reverted by modulating the fractalkine pathway (p < .05). In conclusion, the blockage of the fractalkine pathway seemed to be a possible therapeutic strategy for inflammatory and neuropathic orofacial pain, reducing mechanical hyperalgesia by impairing the phosphorylation of p-38 MAPK and reverting morphological alterations in microglia and SGCs.
Assuntos
Artrite , Neuralgia , Masculino , Animais , Ratos , Hiperalgesia/tratamento farmacológico , Quimiocina CX3CL1 , Neuroglia , Neuralgia/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno , Inibidores de Proteínas Quinases , Dor Facial/tratamento farmacológico , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
The olfactory working memory capacity (OWMC) paradigm is able to detect cognitive deficits in 5XFAD mice (an animal model of Alzheimer's disease [TG]) as early as 3 months of age, while other behavioral paradigms detect cognitive deficits only at 4-5 months of age. Therefore, we aimed to demonstrate that the OWMC paradigm is more sensitive and consistent in the early detection of declines in cognitive function than other commonly used behavioral paradigms. The prefrontal cortex (PFC), retrosplenial cortex (RSC), subiculum (SUB), and amygdala (AMY) of 5XFAD mice were harvested and subjected to immunostaining to detect the expression of ß-amyloid (Aß). Additionally, we compared the performance of 3-month-old male 5XFAD mice on common behavioral paradigms for assessing cognitive function (i.e., the open field [OF] test, novel object recognition [NOR] test, novel object location [NOL] test, Y-maze, and Morris water maze [MWM]) with that on the OWMC task. In the testing phase of the OWMC task, we varied the delay periods to evaluate the working memory capacity (WMC) of wild-type (WT) mice. Significant amyloid plaque deposition was observed in the PFC, RSC, SUB, and AMY of 3-month-old male 5XFAD mice. However, aside from the OWMC task, the other behavioral tests failed to detect cognitive deficits in 5XFAD mice. Additionally, to demonstrate the efficacy of the OWMC task in assessing WMC, we varied the retention delay periods; we found that the WMC of WT mice decreased with longer delay periods. The OWMC task is a sensitive and robust behavioral assay for detecting changes in cognitive function.
Assuntos
Doença de Alzheimer , Transtornos Cognitivos , Disfunção Cognitiva , Masculino , Animais , Camundongos , Memória de Curto Prazo , Cognição , Disfunção Cognitiva/diagnóstico , Placa AmiloideRESUMO
Individuals considered resilient can overcome adversity, achieving normal physical and psychological development, while those deemed vulnerable may not. Adversity promotes structural and functional alterations in the medial prefrontal cortex (mPFC) and hippocampus. Moreover, activity-dependent synaptic plasticity is intricately linked to neuronal shaping resulting from experiences. We hypothesize that this plasticity plays a crucial role in resilience processes. However, there is a notable absence of studies investigating this plasticity and behavioral changes following social adversity at different life stages. Consequently, we evaluated the impact of social adversity during early postnatal development (maternal separation [MS]), adulthood (social defeat [SD]), and a combined exposure (MS + SD) on behavioral outcomes (anxiety, motivation, anhedonia, and social interaction). We also examined cFos expression induced by social interaction in mPFC and hippocampus of adult male rats. Behavioral analyses revealed that SD-induced anhedonia, whereas MS + SD increased social interaction and mitigated SD-induced anhedonia. cFos evaluation showed that social interaction heightened plasticity in the prelimbic (PrL) and infralimbic (IL) cortices, dentate gyrus (DG), CA3, and CA1. Social interaction-associated plasticity was compromised in IL and PrL cortices of the MS and SD groups. Interestingly, social interaction-induced plasticity was restored in the MS + SD group. Furthermore, plasticity was impaired in DG by all social stressors, and in CA3 was impaired by SD. Our findings suggest in male rats (i) two adverse social experiences during development foster resilience; (ii) activity-dependent plasticity in the mPFC is a foundation for resilience to social adversity; (iii) plasticity in DG is highly susceptible to social adversity.
Assuntos
Privação Materna , Plasticidade Neuronal , Córtex Pré-Frontal , Resiliência Psicológica , Animais , Plasticidade Neuronal/fisiologia , Masculino , Ratos , Anedonia/fisiologia , Interação Social , Derrota Social , Hipocampo , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Ratos Wistar , Comportamento Animal/fisiologia , Comportamento Social , Ansiedade/fisiopatologiaRESUMO
In this study, the connection between cognitive behaviors and the adult rodent hippocampus was investigated. Recording field potentials at performant pathway (PP)-hippocampal dentate gyrus (DG) synapses in transverse slices from the dorsal (d), intermediate (i), and ventral (v) hippocampus showed differences in paired-pulse responses and long-term potentiation in rats. The Barnes maze (BM) and passive avoidance (PA) tests indicated a decrease in escape latency and step-through latency in both rats and mice over training days. A decrease in the use of random or sequential strategy while an increase in the use of direct strategy to search for an escape box occurred in both groups. Evaluation of the levels of neurogenesis markers (Ki67 and BrdU/NeuN) by immunofluorescence assay in the dDG, iDG, and vDG revealed a long-axis disparity in the hippocampal dentate baseline cell proliferation and exposure to the BM and PA task changed the profile of baseline cell proliferation along the DG in both rats and mice. Also, these learning experiences changed the profile of BrdU+ /NeuN+ cells along the DG of rats. Quantitation of hippocampal BDNF protein levels using ELISA exhibited no changes in BDNF levels due to learning experiences in rats. We demonstrate that PP-DG synaptic efficacy and neurogenesis are organized along a gradient. Avoidance and escape conditioning themselves are sufficient to change and calibrate adult neurogenesis along the hippocampal long axis in rodents. Further research will be required to determine the precise mechanisms underlying the role of experience-derived neuroplasticity in cognitive function and decline.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Roedores , Masculino , Ratos , Camundongos , Animais , Bromodesoxiuridina , Hipocampo , NeurogêneseRESUMO
The ventral subiculum regulates emotion, stress responses, and spatial and social cognition. In our previous studies, we have demonstrated anxiety- and depression-like symptoms, deficits in spatial and social cognition in ventral subicular lesioned (VSL) rats, and restoration of affective and cognitive behaviors following photoperiod manipulation (short photoperiod regime, SPR; 6:18 LD cycle). In the present study, we have studied the impact of VSL on sleep-wake behavioral patterns and the effect of SPR on sleep-wakefulness behavior. Adult male Wistar rats subjected to VSL demonstrated decreased wake duration and enhanced total sleep time due to increased non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS). Power spectral analysis indicated increased delta activity during NREMS and decreased sigma band power during all vigilance states. Light is one of the strongest entrainers of the circadian rhythm, and its manipulation may have various physiological and functional consequences. We investigated the effect of 21-day exposure to SPR on sleep-wakefulness (S-W) behavior in VSL rats. We observed that SPR exposure restored S-W behavior in VSL rats, resulting in an increase in wake duration and a significant increase in theta power during wake and REMS. This study highlights the crucial role of the ventral subiculum in maintaining normal sleep-wakefulness patterns and highlights the effectiveness of photoperiod manipulation as a non-pharmacological treatment for reversing sleep disturbances reported in mood and neuropsychiatric disorders like Alzheimer's disease, bipolar disorder, and major depressive disorder, which also involve alterations in circadian rhythm.
Assuntos
Eletroencefalografia , Hipocampo , Fotoperíodo , Ratos Wistar , Sono , Vigília , Animais , Masculino , Vigília/fisiologia , Ratos , Hipocampo/fisiopatologia , Sono/fisiologia , Ritmo Circadiano/fisiologiaRESUMO
Similar to the human brain, Drosophila glia may well be divided into several subtypes that each carries out specific functions. Glial GPCRs play key roles in crosstalk between neurons and glia. Drosophila Lgr4 (dLgr4) is a human relaxin receptor homolog involved in angiogenesis, cardiovascular regulation, collagen remodeling, and wound healing. A recent study suggests that ilp7 might be the ligand for Lgr4 and regulates escape behavior of Drosophila larvae. Here we demonstrate that Drosophila Lgr4 expression in glial cells, not neurons, is necessary for early development, adult behavior, and lifespan. Reducing the Lgr4 level in glial cells disrupts Drosophila development, while knocking down other LGR family members in glia has no impact. Adult-specific knockdown of Lgr4 in glia but not neurons reduce locomotion, male reproductive success, and animal longevity. The investigation of how glial expression of Lgr4 contributes to this behavioral alteration will increase our understanding of how insulin signaling via glia selectively modulates neuronal activity and behavior.
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Proteínas de Drosophila , Drosophila , Neuroglia , Receptores Acoplados a Proteínas G , Animais , Masculino , Encéfalo , Neurônios , Receptores de Neuropeptídeos , Receptores Acoplados a Proteínas G/genética , Proteínas de Drosophila/genéticaRESUMO
Despite evidence of the beneficial effects of cannabidiol (CBD) in animal models of cocaine use disorder (CUD), CBD neuronal mechanisms remain poorly understood. This study investigated the effects of CBD treatment on brain glucose metabolism, in a CUD animal model, using [18F]FDG positron emission tomography (PET). Male C57Bl/6 mice were injected with cocaine (20 mg/kg, i.p.) every other day for 9 days, followed by 8 days of CBD administration (30 mg/kg, i.p.). After 48 h, animals were challenged with cocaine. Control animals received saline/vehicle. [18F]FDG PET was performed at four time points: baseline, last day of sensitization, last day of withdrawal/CBD treatment, and challenge. Subsequently, the animals were euthanized and immunohistochemistry was performed on the hippocampus and amygdala to assess the CB1 receptors, neuronal nuclear protein, microglia (Iba1), and astrocytes (GFAP). Results showed that cocaine administration increased [18F]FDG uptake following sensitization. CBD treatment also increased [18F]FDG uptake in both saline and cocaine groups. However, animals that were sensitized and challenged with cocaine, and those receiving only an acute cocaine injection during the challenge phase, did not exhibit increased [18F]FDG uptake when treated with CBD. Furthermore, CBD induced modifications in the integrated density of NeuN, Iba, GFAP, and CB1R in the hippocampus and amygdala. This is the first study addressing the impact of CBD on brain glucose metabolism in a preclinical model of CUD using PET. Our findings suggest that CBD disrupts cocaine-induced changes in brain energy consumption and activity, which might be correlated with alterations in neuronal and glial function.
Assuntos
Canabidiol , Cocaína , Camundongos , Animais , Masculino , Canabidiol/farmacologia , Canabidiol/metabolismo , Glucose/metabolismo , Fluordesoxiglucose F18/metabolismo , Encéfalo/metabolismo , Cocaína/farmacologia , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Heat shock proteins (HSPs) as an adjuvant induce antigen-specific immunity through facilitating antigen presentation and stimulating T cells. In this study, the immunostimulatory properties of two major fragments of Hsp70 (N-Hsp70(aa 1-387) with ATPase property and C-Hsp70 (aa 508-641) with peptide-binding capacity) and the full length of Hsp27 as vaccine adjuvants were evaluated to boost HIV-1 Nef antigen-specific immunity in both in vitro and in vivo experiments. METHODS: At first, the nanoparticles harbouring DNA fusion constructs (i.e. N-Hsp70-Nef, C-Hsp70-Nef and Hsp27-Nef) complexed with HIV Rev (34-50) cell-penetrating peptide were generated to deliver DNA into the cells. Then, the recombinant Nef, Hsp27-Nef, N-Hsp70-Nef and C-Hsp70-Nef proteins were generated in E.coli expression system. Next, the immunostimulatory properties of these fusion constructs were evaluated in both in vitro and in vivo studies. Finally, the secretion of main cytokines from single-cycle replicable (SCR) HIV-1 virion-exposed splenocytes was investigated. RESULTS: Our data showed that the stable and non-toxic DNA/Rev nanoparticles could successfully deliver the genes of interest into the cells. Moreover, higher secretion of antibodies and cytokines was detected in mice receiving the Hsp-Nef constructs than in mice receiving Nef antigen. The C-Hsp70 was also superior for inducing Nef-specific Th1 and CTL immunity compared with N-Hsp70 and Hsp27. The T-cell activity was maintained in the SCR-exposed splenocytes, especially the splenocytes of mice receiving the C-Hsp70-Nef regimen. CONCLUSION: Altogether, these findings demonstrate the significance of Hsps as enhancers of antigen-specific immunity. Notably, the C-Hsp70 region showed better adjuvant properties for inducing cellular immunity in the improvement of HIV-1 therapeutic vaccines.
Assuntos
Infecções por HIV , HIV-1 , Vacinas , Camundongos , Animais , Humanos , HIV-1/genética , Infecções por HIV/prevenção & controle , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico , Adjuvantes Imunológicos/farmacologia , Citocinas , DNARESUMO
Bacteria-derived outer membrane vesicles (OMVs) can be engineered to incorporate foreign antigens. This study explored the potential of ClearColi™-derived OMVs as a natural adjuvant and a carrier (recombinant OMVs or rOMVs) for development of an innovative therapeutic vaccine candidate harboring HIV-1 Nef and Nef-Tat antigens. Herein, the rOMVs containing CytolysinA (ClyA)-Nef and ClyA-Nef-Tat fusion proteins were isolated from ClearColi™ strain. The presence of Nef and Nef-Tat proteins on their surface (rOMVNef and rOMVNef-Tat) was confirmed by western blotting after proteinase K treatment. Immune responses induced by Nef and Nef-Tat proteins emulsified with Montanide® ISA720 or mixed with OMVs, and also rOMVNef and rOMVNef-Tat were investigated in BALB/c mice. Additionally, the potency of splenocytes exposed to single-cycle replicable (SCR) HIV-1 virions was assessed for the secretion of cytokines in vitro. Our findings showed that the rOMVs as an antigen carrier (rOMVNef and rOMVNef-Tat) induced higher levels of IgG2a, IFN-γ and granzyme B compared to OMVs as an adjuvant (Nef + OMV and Nef-Tat + OMV), and also Montanide® ISA720 (Nef + Montanide and Nef-Tat + Montanide). Moreover, IFN-γ level in splenocytes isolated from mice immunized with rOMVNef-Tat was higher than other regimens after exposure to SCR virions. Generally, ClearColi™-derived rOMVs can serve as potent carriers for developing effective vaccines against HIV-1 infection.
Assuntos
Vacinas contra a AIDS , Adjuvantes Imunológicos , Infecções por HIV , HIV-1 , Camundongos Endogâmicos BALB C , Produtos do Gene nef do Vírus da Imunodeficiência Humana , Animais , Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/genética , HIV-1/genética , HIV-1/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética , Produtos do Gene nef do Vírus da Imunodeficiência Humana/imunologia , Camundongos , Adjuvantes Imunológicos/administração & dosagem , Infecções por HIV/prevenção & controle , Infecções por HIV/imunologia , Feminino , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/imunologia , Citocinas/metabolismo , Imunoglobulina G/sangue , Anticorpos Anti-HIV/imunologia , Membrana Externa Bacteriana/metabolismo , Desenvolvimento de Vacinas , Humanos , Portadores de Fármacos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Baço/imunologiaRESUMO
The low temperature activity of Fe-loaded zeolites as selective catalytic reduction of NOx by NH3 (NH3 -SCR) catalysts is a critical drawback for practical application. Here, we found unexpected improvement of low temperature activity by our proposed post-synthetic treatment. An Al-rich zeolite beta (Si/Al=5) is employed as the catalyst support, and the parent sample is dealuminated for higher hydrothermal stability, followed by the liquid-mediated stabilization treatment and impregnation. It is found that stabilized samples feature excellent low temperature activity and high N2 selectivity even for a long-term operation, along with the ability to maintain high NOx conversion after aging. The improved SCR activity should be attributed to abundant acid sites in Al-rich framework and better stabilization of monomeric iron species after the stabilization treatment. Furthermore, the low yield of side product N2 O is probably due to the absence of the generation of NH4 NO3 during NH3 -SCR catalyzed by Fe-loaded zeolites.
RESUMO
Cu-exchanged chabazite (Cu-CHA) is widely used for ammonia assisted selective catalytic reduction of nitrogen oxides (NH3-SCR). The Cu+ ions are at low temperatures solvated by NH3 forming mobile [Cu(NH3)2]+ complexes. The dynamic behaviour of the complexes is critical as O2 adsorption requires a pair of complexes to form a [Cu2(NH3)4O2]2+ peroxo-species over which NO couples with NH3. Here we introduce a first principles-based kinetic Monte Carlo approach to explore the effect of the Al-distribution on the reaction kinetics of NH3-SCR over Cu-CHA. The method allows us to scrutinize the interplay between the pairing of [Cu(NH3)2]+ complexes and the reaction landscape for the NH3-SCR reaction over the peroxo-complex. The Al-distribution affects the stability of the [Cu(NH3)2]+ pairs as well as the kinetic parameters of the SCR-reaction. The turn-over frequency is determined by the stability of the [Cu(NH3)2]+ pairs and the relative strength of NO and NH3 adsorption once a pair is present. The results establish the hierarchy of effects that influences the performance of Cu-CHA over NH3-SCR and provide a computational basis for further development of the Cu-CHA material.
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With the introduction of increasingly strict emission regulations, reducing nitrogen oxide (NOx ) emissions and nitrous oxide (N2 O) production from diesel engines have become the focus of research. At high temperature, the reaction of NO2 in the catalyst generates the intermediate product NH4 NO3 , which first crystallizes below 300 °C. These crystals tend to block the pores and inhibit the reaction. Subsequently, N2 O is produced through the decomposition of NH4 NO3 , leading to additional pollution. Therefore, the concentration of NO2 has a direct impact on both the NOx conversion efficiency and the generation of N2 O, requiring consideration of the optimal proportion of NO2 in SCR. Considering these two factors, it is concluded that the optimal amount of NO2 varies with temperature. To improve the NOx conversion rate of the Cu-SSZ-13 catalyst at low temperatures and reduce N2 O generation, the optimal NO2 ratio of the Cu-SSZ-13 catalyst under various operating conditions is studied using numerical simulations. As the temperature rises, the optimal NO2 /NOx ratio first increases and then decreases. Under the optimal NO2 /NOx ratio, the NOx conversion rate significantly increases, while N2 O generation decreases considerably. The optimal NO2 /NOx ratio also provides suggestions for the optimization of the DOC-DPF-DCR system.
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Concealed information test (CIT) has been utilized for long to perform single measurements. The combination of multiple measures outperforms single measures because of the diverse cognitive processes they reflect and the reduction in random errors facilitated by multiple measures. To further explore the performance of the CIT with multiple measurements, 57 participants were recruited and randomly assigned into guilty and innocent groups. Subsequently, simultaneously recorded reaction time (RT), skin conductance responses (SCRs), heart rate (HR), and neuroimaging data were collected from functional near-infrared spectroscopy (fNIRS) to detect participants' concealed information in a standard CIT. The results demonstrated that all indicators including RT (area under the curve (AUC) = 0.87), SCRs (AUC = 0.79), HR (AUC = 0.78), and fNIRS (channel 8, AUC = 0.85) could differentiate guilty and innocent groups. Importantly, the use of multiple indicators achieved higher detection efficiency (AUC = 0.96) compared to the use of any single indicator. These results illustrate the effectiveness and feasibility of integrating multiple indicators for concealed information detection in CIT.
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The impact of water on catalyst activity remains inconclusive due to its dependence on the specific reaction environment. To maximize the exploitation of water's promoting effect, we employed ammonia selective catalytic reduction (NH3-SCR) as a probe reaction and proposed a phosphorus modification strategy for Cu-ZSM-5 catalysts. The objective of this approach was to construct water-adaptive microstructures through directional arrangement. To investigate the effect of phosphorus on the transformation of framework copper sites in humid environments, we conducted comprehensive characterizations and density functional theory calculation. Results reveal that water molecules cleave the oxygen bridges between phosphorus oxide and copper, leading to the formation of active isolated [Cu(OH)]+ groups and phosphate. The phosphate species weaken the interaction between exchanged Cu2+ groups and the zeolite framework, leading to the generation of highly migratory hydrated Cu2+ species. This work will potentially guide the rational design of water-adaptive catalysts for gas pollution abatement in a humid environment.
Assuntos
Amônia , Fósforo , Água , Fósforo/química , Água/química , Amônia/química , Catálise , Umidade , Zeolitas/química , Cobre/químicaRESUMO
Water is ubiquitous in various heterogeneous catalytic reactions, where it can be easily adsorbed, chemically dissociated, and diffused on catalyst surfaces, inevitably influencing the catalytic process. However, the specific role of water in these reactions remains unclear. In this study, we innovatively propose that H2O-driven surface lattice oxygen activation in γ-MnO2 significantly enhances low-temperature NH3-SCR. The proton from water dissociation activates the surface lattice oxygen in γ-MnO2, giving rise to a doubling of catalytic activity (achieving 90% NO conversion at 100 °C) and remarkable stability. Comprehensive in situ characterizations and calculations reveal that spontaneous proton diffusion to the surface lattice oxygen reduces the orbital overlap between the protonated oxygen atom and its neighboring Mn atom. Consequently, the Mn-O bond is weakened and the surface lattice oxygen is effectively activated to provide excess oxygen vacancies available for converting O2 into O2-. Therefore, the redox property of Mn-H is improved, leading to enhanced NH3 oxidation-dehydrogenation and NO oxidation processes, which are crucial for low-temperature NH3-SCR. This work provides a deeper understanding and fresh perspectives on the water promotion mechanism in low-temperature NOx elimination.