RESUMEN
Water splitting to produce hydrogen is known as an effective way to alleviate the energy crisis, but the slow kinetics of the oxygen evolution reaction (OER) has been seriously restricting the development of water splitting technology. Therefore, low cost and high efficiency OER electrocatalysts have become substitutes for traditional noble metal-based catalysts. In this work, CuCoO2 nanosheets (denoted by CCO2) were successfully synthesized under the regulation of surfactants and a solvent polyethylene glycol (PEG) by a solvothermal route using Cu-BTC and Co(NO3)2·6H2O as reactants. The experimental results confirmed that PEG addition could further reduce significantly the crystal size of the CCO2 nanosheets, i.e., the size was about 150 nm and the thickness was 13 nm. The Ni@CCO2 electrode exhibits outstanding OER performance in 1.0 M KOH electrolyte, which shows the overpotential at 10 mA cm-2 is 378 mV, and the Tafel slope is 85 mV dec-1. Moreover, the CCO2 nanosheets exhibit good structural and compositional stability after the 18 h constant current OER test. Therefore, this work may offer a novel insight into enhancing the OER performance of CuCoO2 catalysts by decreasing their crystal size, and using a solvothermal route.
RESUMEN
The key step for hydrogen production through water electrolysis is the development of highly efficient and inexpensive oxygen evolution reaction (OER) catalysts. In this work, we report the successful synthesis of a nanostructured Fe-doped cobalt-based telluride (Fe-doped CoTe2) catalyst on Co foam by a simple one-step hydrothermal synthesis method, which shows excellent OER performance. The influences of Fe doping amounts and reaction temperatures on the morphology, structure, composition, and the OER performance of cobalt-based tellurides have been systematically studied. The optimal sample Co@0.3 g FeCoTe2-200 exhibits a low overpotential of 300 mV at a current density of 10 mA cm-2, and a small Tafel slope of 36.99 mV dec-1, outperforming the undoped cobalt telluride catalysts (Co@CoTe2-200). The Co@0.3 g FeCoTe2-200 electrode also reveals a small overpotential degradation of around 26 mV after an 18-hour continuous OER process. These results unambiguously confirm that Fe doping helps improve the OER activity and long-term catalytic stability. The superior performance of nanostructured Fe-doped CoTe2 can be attributed to the porous structure and the synergistic effect of Co and Fe elements. This study provides a new approach for the preparation of bimetallic telluride catalysts with enhanced OER performance, and Fe-doped CoTe2 holds substantial promise for use as a high-efficiency, cost-effective catalyst for alkaline water electrolysis.
RESUMEN
In this work, two different solvothermal synthesis routes were employed to prepare MOF-derived CuCoO2 (CCO) nanocrystals for electrocatalytic oxygen evolution reaction (OER) application. The effects of the reductants (ethylene glycol, methanol, ethanol, and isopropanol), NaOH addition, the reactants, and the reaction temperature on the structure and morphology of the reaction product were investigated. In the first route, Cu-BTC derived CCO (CCO1) nanocrystals with a size of â¼214 nm and a specific surface area of 4.93 m2 g-1 were prepared by using Cu-BTC and Co(NO3)2·6H2O as the Cu and Co source, respectively. In the second route, ZIF-67 derived CCO (CCO2) nanocrystals with a size of â¼146 nm and a specific surface area of 11.69 m2 g-1 were prepared by using ZIF-67 and Cu(NO3)2·3H2O as the Co and Cu source, respectively. Moreover, the OER performances of Ni foam supported CCO1 (Ni@CCO1) and CCO2 (Ni@CCO2) electrodes were evaluated in 1.0 M KOH solution. Ni@CCO2 demonstrates a better OER catalytic performance with a lower overpotential of 394.5 mV at 10 mA cm-2, a smaller Tafel slope of 82.6 mV dec-1, and long-term durability, which are superior to those of some previously reported delafossite oxide or perovskite oxide catalysts. This work reveals the preparation method and application potential of CCO electrocatalysts by using Cu-BTC/ZIF-67 as the precursor, providing a new approach for the preparation of delafossite oxide CCO and the enhancement of their OER performances.
RESUMEN
In this work, nickel (Ni) doped Cu-BTC derived CuCoO2 (CCO) was successfully synthesized by a solvothermal method, and the effects of Ni doping concentration (such as 1 at%, 3 at% and 5 at%) on the crystal structure, morphology, composition and oxygen evolution reaction (OER) catalytic performance of CuCoO2 were investigated. X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) were carried out to characterize the crystal structure, morphology and chemical composition of CuCoO2 crystals. The results show that Ni ions have been successfully doped into the CuCoO2 crystal structure and this Ni introduction can reduce its grain size, and 5 at% Ni doped CCO (5NCCO) nanosheets exhibit an average particle size of 386 nm with thicknesses around 28 nm. The optimal Ni@5NCCO electrode needs an overpotential of 409 mV to generate a current density of 10 mA cm-2 and is able to sustain galvanostatic OER electrolysis for 18 hours with only a minor degradation of 30 mV. The enhanced OER performance may be due to the increase in the catalytic activity area and the improvement in conductivity, which is caused by a decrease in grain size and the formation of a porous structure for Ni doped Cu-BTC derived CuCoO2.
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Gliomas are common malignant tumors of the central nervous system. Despite the surgical resection and postoperative radiotherapy and chemotherapy, the prognosis of glioma remains poor. Therefore, it is important to reveal the molecular mechanisms that promotes glioma progression. Microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. The GEO2R tool was used to identify 428 differentially expressed genes (DEGs) and a core module from three microarray datasets. Heat maps were drawn based on DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the DAVID database. The core module was significantly involved in several KEGG pathways, such as "cell cycle", "viral carcinogenesis", "progesterone-mediated oocyte maturation", "p53 signaling pathway". The protein-protein interaction (PPI) networks and modules were built using the STRING database and the MCODE plugin, respectively, which were visualized using Cytoscape software. Identification of hub genes in the core module using the CytoHubba plugin. The top modular genes AURKA, CDC20, CDK1, CENPF, and TOP2A were associated with glioma development and prognosis. In the Human Protein Atlas (HPA) database, CDC20, CENPF and TOP2A have significant protein expression. Univariate and multivariate cox regression analysis showed that only CENPF had independent influencing factors in the CGGA database. GSEA analysis found that CENPF was significantly enriched in the cell cycle, P53 signaling pathway, MAPK signaling pathway, DNA replication, spliceosome, ubiquitin-mediated proteolysis, focal adhesion, pathway in cancer, glioma, which was highly consistent with previous studies. Our study revealed a core module that was highly correlated with glioma development. The key gene CENPF and signaling pathways were identified through a series of bioinformatics analysis. CENPF was identified as a candidate biomarker molecule.
Asunto(s)
Perfilación de la Expresión Génica , Glioma , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Glioma/genética , Humanos , Mapas de Interacción de ProteínasRESUMEN
It is urgent to explore cost-effective, high-efficiency, and durable electrocatalysts for electrochemical water splitting due to the rapidly increasing energy consumption. In this work, we successfully synthesize Ca-doped CuCoO2 nanosheets (CCCO-P NSs) with different Ca2+ dopants (such as 3, 5, and 10 atom %) by a surfactant-modified hydrothermal reaction with polyvinylpyrrolidone (PVP) addition. The oxygen evolution reaction (OER) performances of these CCCO-P NSs in 1.0 M KOH are investigated. An optimal nickel foam supported CCCO-P2 NSs (Ni@CCCO-P2, 5 atom % Ca-doped) electrode requires low overpotential of 470 mV to afford the current density of 10 mA cm-2 and small Tafel slope of 96.5 mV dec-1. Furthermore, the Ni@CCCO-P2 electrode displays outstanding long-term stability during the galvanostatic OER electrolysis for 18 h with a little degradation of 32 mV. The improvement of OER performances for CCCO-P2 NSs could be attributed to their higher active surface area, more active sites (Co vacancies defect and Co3+/Co4+ redox pairs), and higher electrical conductivity. This work highlights the joint effect of surfactant and Ca doping for preparing CuCoO2 with nanosheet-like morphology and porous crystal structure, which is favorable for enhancing their OER performance.
RESUMEN
In this work, we present the hydrothermal synthesis of delafossite oxide Ca-doped CuCoO2 (CCCaO) nanosheets at a low temperature of 100 °C. The crystal phase, morphology and chemical composition of these CuCoO2 (CCO) based samples were comprehensively characterized by powder X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. The size of CCCaO nanosheets decreased with increasing Ca dopant concentration, and the optimized CCCaO nanosheets (â¼490 nm in lateral size and â¼15 nm in thickness) were much smaller than CCO nanocrystals (â¼540 nm in lateral size and 85 nm in thickness). The specific surface area of these CCO based samples increased with increasing Ca content, and the optimized CCCaO nanosheets present a high BET surface area of 28 m2 g-1. XPS and Raman spectroscopy analyses indicate Ca2+ dopant substitution on the Cu+ site in CCCaO nanosheets. Moreover, the effects of Ca2+ doping on the optical and electrical properties of these CCO based samples were further studied. The optical properties measured at room temperature show high absorbability (up to 90%) in the ultraviolet-visible-near infrared (UV-VIS-NIR) region, and the indirect band gap shows a significant blue-shift with increasing Ca2+ concentration. The CCO nanocrystals possess a higher electrical conductivity than the CCCaO nanosheets, and present good conductivities of around 12.81, 4.47 and 0.69 s m-1 for the CCO and CCCaO samples at room temperature. The facile fabrication process, tunable crystallite sizes, and excellent optical absorption and electrical properties of these CCO based nanomaterials are encouraging for the development of future applications in photoelectric devices.
RESUMEN
Thrombin and activated protein C (APC) are known coagulation factors that exhibit profound effects in brain by acting on the protease activated receptor (PAR). The wild type (WT) proteases appear to impact cell survival powerfully, and therapeutic forms of APC are under development. Engineered recombinant thrombin or APC were designed to separate their procoagulant or anticoagulant effects from their cytoprotective properties. We measured vascular disruption and neuronal degeneration after a standard rodent filament stroke model. For comparison to a robust anticoagulant, we used a GpIIb/IIIa inhibitor, GR144053. During 2â¯h MCAo both WT murine APC and its mutant, 5A-APC, significantly decreased neuronal death 30â¯min after reperfusion. During 4â¯h MCAo, only 5A-APC significantly protected neurons but both WT-APC and 5A-APC exacerbated vascular disruption during 4â¯h MCAo. Human APC mutants appeared to reduce 24â¯h neuronal injury significantly when given after 2â¯h delay after MCAo. In contrast, 24â¯h vascular damage was worsened by high doses of WT and mutant APCs, although only statistically significantly for high dose 3K3A-APC. Mutated thrombin worsened vascular damage significantly without affecting neuron damage. GR144053 failed to ameliorate vascular disruption or neuronal injury despite significant anticoagulation. Differential effects on neurons and the vasculature were demonstrated using wild-type and mutated proteases. The mutants murine 3K3A-APC and 5A-APC protected neurons in this rodent model but in high doses worsened vascular leakage. Cytoactive effects of plasma proteases may be separated from their coagulation effects. Further studies should explore impact of dose and timing on cytoactive and vasculoactive properties of these drugs.
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Proteína C/metabolismo , Receptores Proteinasa-Activados/metabolismo , Trombina/metabolismo , Animales , Anticoagulantes/uso terapéutico , Encéfalo/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Ligandos , Masculino , Neuronas/metabolismo , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Piperazinas/farmacología , Piperidinas/farmacología , Proteína C/farmacología , Ratas , Ratas Sprague-Dawley , Receptor PAR-1/metabolismo , Accidente Cerebrovascular/tratamiento farmacológico , Trombina/farmacologíaRESUMEN
Calcium silicate monolith was prepared by the hydrothermal reaction of a slurry of SiO2 , calcium hydroxide, and surfactant (OP-10) obtained by high-energy ball milling, followed by drying at ambient pressure. By using this strategy, the shrinkage due to the collapse of pores during the drying of porous materials, which is a commonly observed phenomena, was successfully avoided. It has a unique microstructure of hierarchical macro-/mesoporous ultrathin calcium silicate nanosheets with a layered gyrolite crystalline structure. Very interestingly, the calcium silicate nanosheets can be peeled off to give a single-layer nanosheet (1.23â nm) of gyrolite by ultrasonication. The monolith has a low apparent density (0.073â g cm(-3) ) and low thermal conductivity (0.0399â W K(-1) m(-1) ). The reasons behind why the formation of the unique hierarchical macro-/mesoporous ultrathin nanosheets avoids shrinkage during the hydrothermal reaction and drying, and considerably decreases the thermal conductivity, is discussed.
RESUMEN
Cerebral postischemic reperfusion injury is defined as deterioration of ischemic brain tissue that parallels and antagonizes the benefits of restoring cerebral circulation after therapeutic thrombolysis for acute ischemic stroke. To understand the paradox of injury caused by treatment, we first emphasize the phenomenon in which recanalization of an occluded artery does not lead to tissue reperfusion. Additionally, no-reflow after recanalization may be due to injury of the neurovascular unit, distal microthrombosis, or both, and certainly worsens outcome. We examine the mechanism of molecular and subcellular damage in the neurovascular unit, notably oxidative stress, mitochondrial dysfunction, and apoptosis. At the level of the neurovascular unit, which mediates crosstalk between the damaged brain and systemic responses in blood, we summarize emerging evidence demonstrating that individual cell components play unique and cumulative roles that lead to damage of the blood-brain barrier and neurons. Furthermore, we review the latest developments in establishing a link between the immune system and microvascular dysfunction during ischemic reperfusion. Progress in assessing reperfusion injury has also been made, and we review imaging studies using various magnetic resonance imaging modalities. Lastly, we explore potential treatment approaches, including ischemic preconditioning, postconditioning, pharmacologic agents, and hypothermia.
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Edema Encefálico/fisiopatología , Isquemia Encefálica/fisiopatología , Hemorragias Intracraneales/fisiopatología , Daño por Reperfusión/fisiopatología , Animales , Edema Encefálico/patología , Isquemia Encefálica/patología , Isquemia Encefálica/terapia , Humanos , Hemorragias Intracraneales/patología , Daño por Reperfusión/patologíaRESUMEN
STUDY DESIGN: This is a case report. OBJECTIVE: To report a 3-dimensional (3D) rotational C-arm conebeam computed tomography (CT) (DynaCT) angiography generating computed tomographic data concurrently with spinal angiographic datasets. This technology allowed 3D modeling of the anterior spinal arterial supply in juxtaposition to a hypervascular tumor mass, thus affording unprecedented guidance in presurgical planning. SUMMARY OF BACKGROUND DATA: An enhanced demonstration of spatial relationships between the vascular elements and their adjacent soft-tissue structures is needed to visualize the minute anterior spinal artery optimally. METHODS: A 76-year-old male with a history of renal cell carcinoma metastasis to the T6 vertebra 1 year prior, presented with worsening myelopathy caused by severe spinal cord compression at T6 level, and a plan for surgical decompression was established. Because of the hypervascular nature of this renal cell carcinoma metastasis, preoperative embolization was requested to minimize blood loss during the operation. A digital subtraction angiogram identified the major arterial contribution to the tumor to also supply the radiculomedullary branch to the anterior spinal artery. To further characterize this blood supply, a rotational DynaCT angiography was performed. RESULTS: The rotationally acquired data were processed generating volumetric CT datasets demonstrating the 3D relationships of the anterior spinal artery, the blood supply to the tumor and the adjacent soft-tissue and bony structures. A shared blood supply to both the tumor mass and the anterior spinal artery from the left T6 segmental artery was confirmed. The dual nature of this blood supply presented increased risk of ischemic spinal cord injury by possible nontarget embolization. Therefore, the embolization was deferred. CONCLUSION: The DynaCT angiography precisely characterized the complex blood supply of a hypervascular vertebral tumor mass in relation to a shared arterial supply to the thoracic spinal cord. The optimal visualization properly aided presurgical planning. LEVEL OF EVIDENCE: N/A.
Asunto(s)
Carcinoma de Células Renales/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Vértebras Torácicas/diagnóstico por imagen , Anciano , Angiografía de Substracción Digital , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/cirugía , Descompresión Quirúrgica , Humanos , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/cirugía , Vértebras Torácicas/patología , Vértebras Torácicas/cirugíaRESUMEN
Neuronal precursor cell migration in the developing mammalian brain is a complex process requiring the coordinated interaction of numerous proteins. We have recently shown that amyloid precursor protein (APP) plays a role in migration into the cortical plate through its interaction with two cytosolic signaling proteins, disabled 1 (DAB1) and disrupted in schizophrenia 1 (DISC1). In order to identify extracellular factors that may signal through APP to regulate migration, we performed an unbiased mass spectrometry-based screen for factors that bind to the extracellular domain of APP in the rodent brain. Through this screen, we identified an interaction between APP and pancortins, proteins expressed throughout the developing and mature cerebral cortex. Via co-immunoprecipitation, we show that APP interacts with all four of the mammalian pancortin isoforms (AMY, AMZ, BMY, BMZ). We demonstrate that the BMZ and BMY isoforms of pancortin can specifically reduce ß-secretase- but not α-secretase-mediated cleavage of endogenous APP in cell culture, suggesting a biochemical consequence of the association between pancortins and APP. Using in utero electroporation to overexpress and knock down specific pancortin isoforms, we reveal a novel role for pancortins in migration into the cortical plate. Interestingly, we observe opposing roles for alternate pancortin isoforms, with AMY overexpression and BMZ knock down both preventing proper migration of neuronal precursor cells. Finally, we show that BMZ can partially rescue a loss of APP expression and that APP can rescue effects of AMY overexpression, suggesting that pancortins act in conjunction with APP to regulate entry into the cortical plate. Taken together, these results suggest a biochemical and functional interaction between APP and pancortins, and reveal a previously unidentified role for pancortins in mammalian cortical development.
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Movimiento Celular/fisiología , Proteínas de la Matriz Extracelular/metabolismo , Glicoproteínas/metabolismo , Isoformas de Proteínas/metabolismo , Animales , Western Blotting , Línea Celular , Movimiento Celular/genética , Corteza Cerebral/metabolismo , Electroporación , Proteínas de la Matriz Extracelular/genética , Glicoproteínas/genética , Humanos , Inmunoprecipitación , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Isoformas de Proteínas/genética , RatasRESUMEN
Pelvic schwannomas are rare; it is even more rare for a pelvic schwannoma to occur concurrently with a colon cancer. The authors report the case of a 62-year-old woman with a cecal mass that was surgically removed and the histopathologic diagnosis was adenocarcinoma of the colon. Meanwhile, aretroperitonealpelvic nodalmasswas detected as questionable metastasis of the primary tumor. A subsequent computed tomography-guided fine-needle biopsy was carried out to establish the tumor stage. Surprisingly, the fine-needle biopsy revealed a benign schwannoma. This unusual case posed a dilemma in postoperative staging of the colon cancer.
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Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Ciego , Neoplasias del Colon , Neurilemoma/patología , Neoplasias Pélvicas/patología , Neoplasias del Sistema Nervioso Periférico/patología , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adenocarcinoma/fisiopatología , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biopsia con Aguja Fina , Antígeno Carcinoembrionario/sangre , Ciego/patología , Ciego/cirugía , Neoplasias del Colon/sangre , Neoplasias del Colon/patología , Neoplasias del Colon/fisiopatología , Neoplasias del Colon/terapia , Terapia Combinada , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Primarias Múltiples , Neurilemoma/fisiopatología , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Neoplasias Pélvicas/fisiopatología , Neoplasias del Sistema Nervioso Periférico/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
In vitro study of primary neuronal cultures allows for quantitative analyses of neurite outgrowth. In order to study how genetic alterations affect neuronal process outgrowth, shRNA or cDNA constructs can be introduced into primary neurons via chemical transfection or viral transduction. However, with primary cortical cells, a heterogeneous pool of cell types (glutamatergic neurons from different layers, inhibitory neurons, glial cells) are transfected using these methods. The use of in utero electroporation to introduce DNA constructs in the embryonic rodent cortex allows for certain subsets of cells to be targeted: while electroporation of early embryonic cortex targets deep layers of the cortex, electroporation at late embryonic timepoints targets more superficial layers. Further, differential placement of electrodes across the heads of individual embryos results in the targeting of dorsal-medial versus ventral-lateral regions of the cortex. Following electroporation, transfected cells can be dissected out, dissociated, and plated in vitro for quantitative analysis of neurite outgrowth. Here, we provide a step-by-step method to quantitatively measure neuronal process outgrowth in subsets of cortical cells. The basic protocol for in utero electroporation has been described in detail in two other JoVE articles from the Kriegstein lab. We will provide an overview of our protocol for in utero electroporation, focusing on the most important details, followed by a description of our protocol that applies in utero electroporation to the study of gene function in neuronal process outgrowth.
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Corteza Cerebral/fisiología , ADN/administración & dosificación , Electroporación/métodos , Neuronas/fisiología , Animales , Técnicas de Cultivo de Célula/métodos , Corteza Cerebral/citología , Corteza Cerebral/embriología , ADN/genética , Embrión no Mamífero , Femenino , Proteínas Fluorescentes Verdes/análisis , Proteínas Fluorescentes Verdes/genética , Masculino , Neuritas/fisiología , Neuronas/citología , Plásmidos/análisis , Plásmidos/genética , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The compounds 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (HMG Co-A reductase inhibitors, statins) are popular medications for the control of elevated serum cholesterol. Recent evidence has demonstrated a survival benefit to patients who take statins in the premorbid period with severe sepsis, septic shock, or severe trauma. We hypothesized that a similar benefit would be seen in patients with ruptured abdominal aortic aneurysm. STUDY DESIGN: We completed a retrospective review of patients with ruptured abdominal aortic aneurysm in our institution from January 2000 to December 2008. We compared age, gender, mortality rates, and Physiologic and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) scores for all patients who met inclusion and exclusion criteria. We compared hospital and ICU lengths of stay, cardiac morbidity, and number of cardiac events per patient between survivor groups with and without prehospital statin use. We compared mortality, cardiac morbidity, and gender using the Pearson chi-square test, Physiologic and Operative Severity Score for the enumeration of Mortality and Morbidity scores and age using the Student's t-test and lengths of stay using the Mann Whitney-U test. RESULTS: Mortality in the group without prehospital statin use was 63.8%, and in the group with prehospital statin use was 34.8% (p=0.018, odds ratio 0.30 to 0.11). Physiologic and Operative Severity Score for the enumeration of Mortality and Morbidity scores were similar between survivor groups with and without statin use and nonsurvivor groups with and without statin use. Hospital and ICU lengths of stay, cardiac morbidity, and number of cardiac events per patient were not statistically different among survivors. CONCLUSIONS: Prehospital statin use appears to be associated with a significant survival benefit in the ruptured abdominal aortic aneurysm population.
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Aneurisma de la Aorta Abdominal/mortalidad , Rotura de la Aorta/mortalidad , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Anciano , Distribución de Chi-Cuadrado , Femenino , Mortalidad Hospitalaria , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Estudios Retrospectivos , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
During forebrain development the lateral cortical stream (LCS) supplies neurons to structures in the ventral telencephalon including the amygdala and piriform cortex. In the current study, we used spatially directed in utero electroporation and RNAi to investigate mechanisms of migration to the ventral telencephalon. Cells labeled by in utero electroporation of the lateral ventricular zone migrated into the LCS, and entered the lateral neocortex, piriform cortex and amygdala, where they differentiated primarily as pyramidal neurons. RNAi of DCX or LIS1 disrupted migration into amygdala and piriform cortex and caused many neurons to accumulate in the external and amygdalar capsules. RNAi of LIS1 and DCX had similar as well as distinguishable effects on the pattern of altered migration. Combinatorial RNAi of LIS1 and DCX further suggested interaction in the functions of LIS1 and DCX on the morphology and migration of migrating neurons in the LCS. Together, these results confirm that the LCS contributes pyramidal neurons to ventral forebrain structures and reveals that DCX and LIS1 have important functions in this major migratory pathway in the developing forebrain.
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Movimiento Celular/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuropéptidos/metabolismo , Prosencéfalo/embriología , Prosencéfalo/metabolismo , Células Piramidales/metabolismo , Amígdala del Cerebelo/citología , Amígdala del Cerebelo/embriología , Amígdala del Cerebelo/metabolismo , Animales , Diferenciación Celular/genética , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Electroporación , Femenino , Regulación del Desarrollo de la Expresión Génica/genética , Proteínas Asociadas a Microtúbulos/genética , Proteínas del Tejido Nervioso/genética , Vías Nerviosas/citología , Vías Nerviosas/embriología , Vías Nerviosas/metabolismo , Neuropéptidos/genética , Vías Olfatorias/citología , Vías Olfatorias/embriología , Vías Olfatorias/metabolismo , Prosencéfalo/citología , Células Piramidales/citología , Interferencia de ARN , Ratas , Ratas Wistar , Células Madre/citología , Células Madre/metabolismoRESUMEN
Physiological processing of the beta-amyloid precursor protein (APP) generates amyloid beta-protein, which can assemble into oligomers that mediate synaptic failure in Alzheimer's disease. Two decades of research have led to human trials of compounds that chronically target this processing, and yet the normal function of APP in vivo remains unclear. We used the method of in utero electroporation of shRNA constructs into the developing cortex to acutely knock down APP in rodents. This approach revealed that neuronal precursor cells in embryonic cortex require APP to migrate correctly into the nascent cortical plate. cDNAs encoding human APP or its homologues, amyloid precursor-like protein 1 (APLP1) or APLP2, fully rescued the shRNA-mediated migration defect. Analysis of an array of mutations and deletions in APP revealed that both the extracellular and cytoplasmic domains of APP are required for efficient rescue. Whereas knock-down of APP inhibited cortical plate entry, overexpression of APP caused accelerated migration of cells past the cortical plate boundary, confirming that normal APP levels are required for correct neuronal migration. In addition, we found that Disabled-1 (Dab1), an adaptor protein with a well established role in cortical cell migration, acts downstream of APP for this function in cortical plate entry. We conclude that full-length APP functions as an important factor for proper migration of neuronal precursors into the cortical plate during the development of the mammalian brain.
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Precursor de Proteína beta-Amiloide/fisiología , Movimiento Celular/fisiología , Corteza Cerebral , Regulación del Desarrollo de la Expresión Génica/fisiología , Neuronas/fisiología , Interferencia de ARN/fisiología , Animales , Células COS , Corteza Cerebral/citología , Corteza Cerebral/embriología , Corteza Cerebral/metabolismo , Chlorocebus aethiops , Electroporación/métodos , Embrión de Mamíferos , Femenino , Proteínas Fluorescentes Verdes/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Embarazo , ARN Interferente Pequeño/farmacología , Ratas , Ratas Sprague-Dawley , Células Madre/fisiología , Transfección/métodos , Útero/fisiologíaRESUMEN
The brains of individuals with developmental dyslexia have neocortical neuronal migration abnormalities including molecular layer heterotopias, laminar dysplasias, and periventricular nodular heterotopias (PNH). RNA interference (RNAi) of Dyx1c1, a candidate dyslexia susceptibility gene, disrupts neuronal migration in developing embryonic neocortex. Using in utero electroporation, we cotransfected cells in the rat neocortical ventricular zone (VZ) at E14/15 with short hairpin RNA vectors targeting Dyx1c1 along with either plasmids encoding enhanced green fluorescent protein or plasmids encoding monomeric red fluorescent protein only. RNAi of Dyx1c1 resulted in pockets of unmigrated neurons resembling PNH. The pattern of migration of transfected neurons was bimodal, with approximately 20% of the neurons migrating a short distance from the VZ and another 40% that migrated past their expected lamina. Approximately 25% of the transfected brains had hippocampal pyramidal cell migration anomalies. Molecular layer ectopias, which were not related to injection site artifacts, were also seen in 25% of the animals. These results support the hypothesis that targeted disruption of the candidate dyslexia susceptibility gene, Dyx1c1, results in neuronal migration disorders similar to those seen in the brains of dyslexics.
Asunto(s)
Hipocampo/anomalías , Hipocampo/fisiopatología , Neocórtex/anomalías , Neocórtex/fisiopatología , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Neuronas/patología , Proteínas Nucleares/metabolismo , Animales , Movimiento Celular , Proteínas del Citoesqueleto , Silenciador del Gen , Morfogénesis , Ratas , Ratas WistarRESUMEN
Developmental malformations of cortex have been shown to co-occur with language, learning, and other cognitive deficits in humans. Rodent models have repeatedly shown that animals with such developmental malformations have deficits related to auditory processing and learning. More specifically, freeze-lesion induced microgyria as well as molecular layer ectopias have been found to impair rapid auditory processing ability in rats and mice. In humans, deficits in rapid auditory processing appear to relate to later impairments of language. Recently, genetic variants of four different genes involved in early brain development have been proposed to associate with an elevated incidence of developmental dyslexia in humans. Three of these, DYX1C1, DCDC2, and KIAA0319, have been shown by in utero RNAi to play a role in neuronal migration in developing neocortex. The present study assessed the effects of in utero RNAi of Dyx1c1 on auditory processing and spatial learning in rats. Results indicate that RNAi of Dyx1c1 is associated with cortical heterotopia and is suggestive of an overall processing deficit of complex auditory stimuli in both juvenile and adult periods (p=.051, one-tail). In contrast, adult data alone reveal a significant processing impairment among RNAi treated subjects compared to shams, indicating an inability for RNAi treated subjects to improve detection of complex auditory stimuli over time (p=.022, one-tail). Further, a subset of RNAi treated rats exhibited hippocampal heterotopia centered in CA1 (in addition to cortical malformations). Malformations of hippocampus were associated with robust spatial learning impairment in this sub-group (p<.01, two-tail). In conclusion, in utero RNAi of Dyx1c1 results in heterogeneous malformations that correspond to distinct behavioral impairments in auditory processing, and spatial learning.
Asunto(s)
Trastornos de la Percepción Auditiva/etiología , Dislexia/complicaciones , Discapacidades para el Aprendizaje/etiología , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética , Interferencia de ARN/fisiología , Estimulación Acústica , Análisis de Varianza , Animales , Animales Recién Nacidos , Proteínas del Citoesqueleto , Modelos Animales de Enfermedad , Dislexia/genética , Dislexia/patología , Femenino , Humanos , Aprendizaje por Laberinto/fisiología , Ratas , Ratas Wistar , Percepción Espacial/fisiología , Transfección/métodos , Útero/fisiologíaRESUMEN
The genetic basis is now known for several disorders of neuronal migration in the developing cerebral cortex. Identification of the cellular processes mediated by the implicated genes is revealing crucial stages of neuronal migration and has the potential to reveal common cellular causes of neuronal migration disorders. We hypothesize that a newly recognized morphological stage of neuronal migration, the multipolar stage, is vulnerable and is disrupted in several disorders of neocortical development. The multipolar stage occurs as bipolar progenitor cells become radially migrating neurons. Several studies using in utero electroporation and RNAi have revealed that transition out of the multipolar stage depends on the function of filamin A, LIS1 and DCX. Mutations in the genes encoding these proteins in humans cause distinct neuronal migration disorders, including periventricular nodular heterotopia, subcortical band heterotopia and lissencephaly. The multipolar stage therefore seems to be a critical point of migration control and a vulnerable target for disruption of neocortical development. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).