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Synaptic plasticity induced by cocaine and other drugs underlies addiction. Here we elucidate molecular events at synapses that cause this plasticity and the resulting behavioral response to cocaine in mice. In response to D1-dopamine-receptor signaling that is induced by drug administration, the glutamate-receptor protein metabotropic glutamate receptor 5 (mGluR5) is phosphorylated by microtubule-associated protein kinase (MAPK), which we show potentiates Pin1-mediated prolyl-isomerization of mGluR5 in instances where the product of an activity-dependent gene, Homer1a, is present to enable Pin1-mGluR5 interaction. These biochemical events potentiate N-methyl-D-aspartate receptor (NMDAR)-mediated currents that underlie synaptic plasticity and cocaine-evoked motor sensitization as tested in mice with relevant mutations. The findings elucidate how a coincidence of signals from the nucleus and the synapse can render mGluR5 accessible to activation with consequences for drug-induced dopamine responses and point to depotentiation at corticostriatal synapses as a possible therapeutic target for treating addiction.
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Trastornos Relacionados con Cocaína/fisiopatología , Cocaína/metabolismo , Dopamina/metabolismo , Isomerasa de Peptidilprolil/metabolismo , Secuencia de Aminoácidos , Animales , Encéfalo/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Embrión de Mamíferos/metabolismo , Proteínas de Andamiaje Homer , Potenciación a Largo Plazo , Ratones , Datos de Secuencia Molecular , Peptidilprolil Isomerasa de Interacción con NIMA , Fosforilación , Receptores AMPA/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Ácido Kaínico/química , Receptores de Ácido Kaínico/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapsis/metabolismoRESUMEN
Lithium (Li)-metal batteries are promising next-generation energy storage systems. One drawback of uncontrollable electrolyte degradation is the ability to form a fragile and nonuniform solid electrolyte interface (SEI). In this study, we propose the use of a fluorinated carbon nanotube (CNT) macrofilm (CMF) on Li metal as a hybrid anode, which can regulate the redox state at the anode/electrolyte interface. Due to the favorable reaction energy between the plated Li and fluorinated CNTs, the metal can be fluorinated directly to a LiF-rich SEI during the charging process, leading to a high Young's modulus (~2.0â GPa) and fast ionic transfer (~2.59×10-7 â S cm-1 ). The obtained SEI can guide the homogeneous plating/stripping of Li during electrochemical processes while suppressing dendrite growth. In particular, the hybrid of endowed full cells with substantially enhanced cyclability allows for high capacity retention (~99.3 %) and remarkable rate capacity. This work can extend fluorination technology into a platform to control artificial SEI formation in Li-metal batteries, increasing the stability and long-term performance of the resulting material.
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BACKGROUND: Emerging evidence of immunological dysfunction have been described in endometriosis. Dendritic cells (DCs), one of the main antigen-presenting cells, are specialized in the initiation and modulation of the adaptive immune response. Emerging studies demonstrated both endometrial and circulating differences in DCs populations in women with endometriosis. However, the role and mechanism of peritoneal DCs in endometriosis is still unclear. The present study was undertaken to explore the features of peritoneal DCs in the pathogenesis of endometriosis. This study is beneficial to further clarify the cause of endometriosis and provide a new insight into the medical treatment for endometriosis. METHODS: The study included 12 women with endometriosis and 11 women without endometriosis. The C57BL6 mouse model of endometriosis was established by intraperitoneal injection of endometrial segments. The peritoneal DCs of endometriosis patients and mouse models were analyzed by fluorescence associated cell sorting (FACS) examination. RESULTS: Increased cell density of peritoneal DCs were observed in endometriosis patients. Moreover, the proportion of mature DCs (mDCs, CD80highCD1alow cells) in the peritoneal DCs was lower whereas the proportion of immature DCs (iDCs, CD80lowCD1ahigh cells) was increased in endometriosis patients. Similarly, the cell density of peritoneal DCs in murine models increased immediately after the injection of endometrial tissues and reached the highest level at 14 days. In addition, the proportion of mDCs (CD11chighCD80high cells) in the peritoneal DCs decreased immediately after the injection of endometrial tissues and then increased with the time until 42 days, but still lower than the control group. In contrast, the proportion of iDCs (CD11chighCD80low cells) in the peritoneal DCs showed the opposite dynamic changes. However, after treated with LPS, the mDCs proportion was significantly increased, leading to lower volume and weight of the endometriosis lesions. CONCLUSIONS: Increased level of peritoneal DCs facilitated the pathogenesis of endometriosis lesions, especially in the early stage of the disease. Furthermore, peritoneal DCs maturation played an important role in the development of endometriosis.
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Endometriosis , Humanos , Femenino , Animales , Ratones , Endometriosis/patología , Diferenciación Celular , Endometrio/patología , Células DendríticasRESUMEN
Tungsten oxide nanoparticles with high dispersion supported on carbon nanotube (CNT) templates were fabricated by the liquid phase method. Given the isolation effects of the network from CNT bundles, the nano-size H2WO4 and WO3 can be obtained. The photodegradation ability of the WO3/CNTs was evaluated by methylene blue (MB). The degradation rate of MB can reach 94.7% for 30 min, which is superior to that of pure WO3 at 73.1% for 30 min. Furthermore, the degradation rate of the catalyst can reach 83.7% after recycling for five times, thus displaying the excellent stability of the photocatalyst. These results may be attributed to the highly dispersed WO3 nanoparticles and the suppression of electron-hole recombination by CNT templates. This study proves that WO3/CNT photocatalysts have potential applications in environmental and other related fields.
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Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The cause of this degeneration has not been determined, but lack of energy metabolites such as glucose or lactate has been proposed. Lactate is transported exclusively by monocarboxylate transporters, and changes to these transporters alter lactate production and use. Here we show that the most abundant lactate transporter in the central nervous system, monocarboxylate transporter 1 (MCT1, also known as SLC16A1), is highly enriched within oligodendroglia and that disruption of this transporter produces axon damage and neuron loss in animal and cell culture models. In addition, this same transporter is reduced in patients with, and in mouse models of, amyotrophic lateral sclerosis, suggesting a role for oligodendroglial MCT1 in pathogenesis. The role of oligodendroglia in axon function and neuron survival has been elusive; this study defines a new fundamental mechanism by which oligodendroglia support neurons and axons.
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Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Axones/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Neuronas Motoras/patología , Degeneración Nerviosa/metabolismo , Oligodendroglía/metabolismo , Simportadores/metabolismo , Esclerosis Amiotrófica Lateral/genética , Animales , Axones/patología , Línea Celular , Supervivencia Celular , Modelos Animales de Enfermedad , Regulación hacia Abajo , Heterocigoto , Humanos , Ácido Láctico/metabolismo , Ratones , Ratones Transgénicos , Transportadores de Ácidos Monocarboxílicos/deficiencia , Transportadores de Ácidos Monocarboxílicos/genética , Neuronas Motoras/metabolismo , Vaina de Mielina/metabolismo , Transporte de Proteínas , ARN Interferente Pequeño , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1 , Simportadores/deficiencia , Simportadores/genéticaRESUMEN
A new kind of multitetrahedron sheath ternary ZnS-(CdS/Au) hetero-nanorod is prepared, in which one 1D ultrathin ZnS nanorod is integrated with segmented tetrahedron sheaths made of CdS, and more importantly, Au nanoparticles can be decorated in a targeted manner onto the vertexes and edges of CdS tetrahedron sheaths solely, for achieving performance improvement in photoelectric and photochemical conversion applications.
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Astroglia are a morphologically diverse and highly abundant cell type in the CNS. Despite these obvious observations, astroglia still remain largely uncharacterized at the cellular and molecular level. In disease contexts such as amyotrophic lateral sclerosis (ALS), it has been widely shown that astroglia downregulate crucial physiological functions, become hypertrophied, reactive, and toxic to motor neurons. However, little is known about the astroglia-specific transcriptomic changes that occur during ALS disease progression, especially early in disease. To address this, we FACS-isolated pure astroglia from early and mid-symptomatic superoxide dismutase 1 (SOD1) G93A spinal cord and performed microarray sequencing, in hopes to uncover markers and pathways driving astroglia dysfunction in ALS. After extensive analyses, we uncovered genes selectively enriched and downregulated in both control and SOD1 astroglia at both disease points. In addition, we were able to identify genes and pathways differentially expressed that may have relevance with other neurodegenerative diseases, such as Parkinson's and Alzheimer's disease, suggesting a common theme among astroglial dysfunction in neurodegenerative disease. In aggregate, this study sheds light on the common and unique themes of dysfunction that astroglia undergo during neurodegenerative disease progression and provides candidate targets for therapeutic approaches.
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Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patología , Astrocitos/patología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Superóxido Dismutasa-1/genética , Animales , Astrocitos/metabolismo , Progresión de la Enfermedad , Ratones , Ratones Transgénicos , Médula Espinal/metabolismo , Médula Espinal/patología , Superóxido Dismutasa/genética , TranscriptomaRESUMEN
Astrocytes are instrumental to major brain functions, including metabolic support, extracellular ion regulation, the shaping of excitatory signaling events and maintenance of synaptic glutamate homeostasis. Astrocyte dysfunction contributes to numerous developmental, psychiatric and neurodegenerative disorders. The generation of adult human fibroblast-derived induced pluripotent stem cells (iPSCs) has provided novel opportunities to study mechanisms of astrocyte dysfunction in human-derived cells. To overcome the difficulties of cell type heterogeneity during the differentiation process from iPSCs to astroglial cells (iPS astrocytes), we generated homogenous populations of iPS astrocytes using zinc-finger nuclease (ZFN) technology. Enhanced green fluorescent protein (eGFP) driven by the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter was inserted into the safe harbor adeno-associated virus integration site 1 (AAVS1) locus in disease and control-derived iPSCs. Astrocyte populations were enriched using Fluorescence Activated Cell Sorting (FACS) and after enrichment more than 99% of iPS astrocytes expressed mature astrocyte markers including GFAP, S100ß, NFIA and ALDH1L1. In addition, mature pure GFP-iPS astrocytes exhibited a well-described functional astrocytic activity in vitro characterized by neuron-dependent regulation of glutamate transporters to regulate extracellular glutamate concentrations. Engraftment of GFP-iPS astrocytes into rat spinal cord grey matter confirmed in vivo cell survival and continued astrocytic maturation. In conclusion, the generation of GFAP::GFP-iPS astrocytes provides a powerful in vitro and in vivo tool for studying astrocyte biology and astrocyte-driven disease pathogenesis and therapy.
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Astrocitos/fisiología , Ingeniería Celular/métodos , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteínas Fluorescentes Verdes/metabolismo , Animales , Astrocitos/trasplante , Supervivencia Celular/fisiología , Células Cultivadas , Desoxirribonucleasas , Dependovirus/genética , Fibroblastos/fisiología , Genes Reporteros , Vectores Genéticos , Sustancia Gris/citología , Sustancia Gris/fisiología , Sustancia Gris/cirugía , Proteínas Fluorescentes Verdes/genética , Humanos , Células Madre Pluripotentes Inducidas/fisiología , Ratones , Regiones Promotoras Genéticas , Ratas Sprague-Dawley , Médula Espinal/citología , Médula Espinal/fisiología , Médula Espinal/cirugía , Dedos de ZincRESUMEN
Mesorhizobium tianshanense employs MsiA as canavanine exporter, which is upregulated by MsiR, to successfully form a symbiosis with the legume Glycyrrhiza uralensis. In this research, through gel-shift and bacterial two-hybrid examination, MsiR was found to spontaneously form dimers and bind to msiA promoter without additional canavanine. Six truncated forms of MsiR were constructed, and the conserved helix-turn-helix (HTH), substrate-binding, and surface-loop domains were found essential for MsiR functions. Random mutagenesis was used to study the functional sites of MsiR. Seven point mutants were selected, in which three mutants constitutively induced msiA expression without additional canavanine, two mutants partially changed substrate specificity, and the other two were almost null mutants. Results from the site mutation show that the functional subunits (HTH domain, dimerization interface domains, and C-terminal) are important in the conformation and induction ability of MsiR.
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Transporte Biológico/fisiología , Canavanina/metabolismo , Glycyrrhiza uralensis/microbiología , Mesorhizobium/metabolismo , Transporte Biológico/genética , Mesorhizobium/genética , Mutación/genética , Regiones Promotoras Genéticas/genética , Unión Proteica/genética , Conformación Proteica , Simbiosis/genética , Activación TranscripcionalRESUMEN
To investigate the role of RAD001 in the reversing of drug resistance of SGC7901/DDP, we cultured SGC7901/DDP cells with different groups of drugs (RAD001, cisplatin (DDP) alone, or the combination of RAD001 and DDP); after that, we detected the drug sensitivity, cell apoptosis, and levels of P-gp, MRP1, and survivin in the cells of SGC7901/DDP by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphe-nyltetrazolium bromide) assay, flow cytometry, immunohistochemical analysis, and Western blot analysis. There was no significant difference between DDP 2.5-mg/L group and negative control group. When the cells were pretreated with RAD001 2.5, 5 nmol/L, the proliferation of SGC7901/DDP cells was inhibited by DDP 2.5 mg/L significantly, compared to negative control group, DDP 2.5-mg/L group, and RAD001 2.5, 5-nmol/L group, respectively (P < 0.05); there were significant differences between combination groups (P < 0.05). DDP 2.5 mg/L and RAD001 2.5 nmol/L did not induce apoptosis of SGC7901/DDP cells alone (P > 0.05). When SGC7901/DDP cells were pretreated with RAD001 2.5 nmol/L, DDP 2.5 mg/L increased the apoptosis rate significantly compared to groups of control and DDP 2.5 mg/L alone (P < 0.05). Immunohistochemical staining (Table 5, Fig. 2) and Western blot analysis (Fig. 3) indicated that when SGC7901/DDP cells were pretreated with RAD001 2.5 nmol/L, the expression of P-gp, MRP1, and survivin decreased by different degrees. Our results have confirmed that RAD001 in combination with DDP could overcome chemoresistance of SGC7901/DDP cells by decreasing the levels of P-gp, MRP1, and survivin through the mTOR pathway.
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Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Sirolimus/análogos & derivados , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antineoplásicos/farmacología , Western Blotting , Línea Celular Tumoral , Cisplatino/farmacología , Relación Dosis-Respuesta a Droga , Everolimus , Citometría de Flujo , Humanos , Inmunohistoquímica , Proteínas Inhibidoras de la Apoptosis/metabolismo , Concentración 50 Inhibidora , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Sirolimus/farmacología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Survivin , Factores de TiempoRESUMEN
OBJECTIVES: Transabdominal sonography with a gastrointestinal contrast agent has been widely used in China for investigation of digestive disorders. Double-contrast-enhanced sonography combines a gastrointestinal luminal contrast agent with an intravenous contrast agent for imaging of lesions. The purpose of this pilot study was to assess the value of double-contrast-enhanced sonography for preoperative diagnosis of rectal lesions. METHODS: We conducted a prospective single-center study using double-contrast-enhanced sonography of rectal lesions. Patients were administered both rectal and intravenous contrast agents, and imaging was performed transabdominally, transanally, and transrectally. Morphologic characteristics and perfusion parameters were compared between histologically proven adenocarcinomas, adenomas, and inflammatory masses. Perfusion parameters were analyzed with time-intensity curves, measuring the contrast arrival time, time to peak, peak intensity, and area under the curve of the lesions and normal rectal tissue. RESULTS: From January 2009 to September 2012, 420 patients were recruited, with 227 patients meeting inclusion/exclusion criteria and having 232 rectal lesions analyzed (172 rectal adenocarcinomas, 45 adenomas, and 15 inflammatory masses). Adenocarcinomas had variable enhancement patterns. Adenomas were all hypoenhanced in a homogeneous pattern. Inflammatory masses had a hyperenhanced rim with no central enhancement. Time-intensity curve perfusion parameters (arrival time, time to peak, peak intensity, and area under the curve) of rectal adenocarcinomas, adenomas, and inflammatory masses were significantly different compared to normal rectal tissue (P < .05). The differences in the arrival time, peak intensity, and time to peak among the different lesions were also significant (P < .05). CONCLUSIONS: Double-contrast-enhanced sonographic assessment of morphologic enhancement patterns combined with vascularity parameters may help differentiate benign and malignant rectal lesions.
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Adenocarcinoma/diagnóstico por imagen , Medicamentos Herbarios Chinos/administración & dosificación , Fosfolípidos/administración & dosificación , Neoplasias del Recto/diagnóstico por imagen , Hexafluoruro de Azufre/administración & dosificación , Ultrasonografía/métodos , Adenocarcinoma/patología , Administración Intravenosa , Adulto , Medios de Contraste/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias del Recto/patología , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadística como AsuntoRESUMEN
Cardiovascular disease is the greatest health care burden and one of the most common causes of death worldwide. Less is known about the genetic factors that are responsible for predisposition to cardiovascular disease thus; the molecular and genetic mechanisms underlying cardiovascular diseases remain obscure. One important regulator of blood pressure homeostasis is the renin-angiotensin system. The protease renin cleaves angiotensinogen into the inactive decameric peptide angiotensin I (Ang I). Angiotensin-converting enzyme (ACE) catalyzes the cleavage of the Ang I into the active octomer angiotensin II (Ang II). In humans, can ACE polymorphism has been associated with determinants of renal and cardiovascular function and pharmacological inhibition of ACE and Ang II receptors are effective in lowering blood pressure and preventing kidney disease. In addition, inhibition of ACE and Ang II receptors has beneficial effects in heart failure. A homologue of ACE, termed ACE2, has been identified; it is predominantly expressed in the vascular endothelial cells of the kidney and heart. Unlike ACE, ACE2 functions as a carboxypeptidase, cleaving a single residue from AngI, generating Ang1-9, and a single residue from AngII to generate Ang1-7. Nevertheless, the in vivo role of ACE2 in the cardiovascular system and the renin-angiotensin system is not known.
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Enfermedades Cardiovasculares , Humanos , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/farmacología , Células Endoteliales , Sistema Renina-Angiotensina/genética , RiñónRESUMEN
BACKGROUND: Bone is the most common site of metastatic breast cancer (MBC). EDTA is often used to decalcify bony tissue samples to ensure the accurate assessment of antigenicity in MBC. It takes ~24 to 48 hours to decalcify small bone tissues such as bone marrow, which is considered unacceptable given the priority that is often placed on the rapid processing of bone marrow trephine cores. Thus, an effective decalcification method that preserves genetic material is needed. AIM: We performed immunohistochemical studies on surface decalcification (SD) in breast tumors and evaluated the effect of SD on receptor status and human epidermal growth factor receptor 2 (HER2). Fluorescence in situ hybridization was performed on a subset of these tumors to establish a protocol for handling bone specimens for MBC. MATERIALS AND METHODS: Forty-four cases of invasive breast tumors were studied. We compared the immunohistochemical expressions of estrogen receptor (ER), progesterone receptor (PR), Ki67, and HER2 between control tissue (nondecalcified) and parallel tissue subjected to SD with hydrochloric acid. We also evaluated the effect of SD on the fluorescence in situ hybridization expression of HER2. RESULTS: Categorical decreases in ER and PR expression were identified in 9/31 (29.0%) cases without SD and 10/26 (38.5%) cases with SD. HER2 expression changed from equivocal to negative in 4/12 (33.4%) cases. Among the HER2-positive cases, all remained positive after SD. The most significant declines in immunoreactivity occurred with Ki67, with an average decrease from 22% to 13%. The average HER2 copy numbers were 5.37 and 4.76 in the control and SD groups, respectively, and the average HER2/CEP17 ratios were 2.35 and 2.08, respectively. CONCLUSIONS: Overall, SD is an alternative decalcification method in bony metastases to assess ER, PR, and HER2 in MBC.
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Neoplasias de la Mama , Receptores de Estrógenos , Humanos , Femenino , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Biomarcadores de Tumor/metabolismo , Ácido Clorhídrico , Antígeno Ki-67/genética , Inmunohistoquímica , Hibridación Fluorescente in Situ , Receptor ErbB-2/metabolismo , Neoplasias de la Mama/patología , EstrógenosRESUMEN
Heterobasidion annosum is one of the most aggressive pathogens of Pinus forests in Europe, causing considerable economic losses. To detect H. annosum for disease diagnosis and control, we developed a loop-mediated isothermal amplification (LAMP) reaction with a primer set designed from the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) DNA sequences of H. annosum. In our study, this LAMP assay was found to be capable of efficiently amplifying the target gene within 60 min at 63°C. In specificity tests, H. annosum was positively detected, and other species were negative. The detection limit of this assay was found to be 100 pg·µL-1, and the assay was also successfully tested for use with basidiospore suspensions and wood samples. This study provides a rapid method for diagnosing root and butt rot caused by H. annosum, which will be of use in port surveillance of logs imported from Europe.
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Basidiomycota , Basidiomycota/genética , Técnicas de Amplificación de Ácido Nucleico , Europa (Continente)RESUMEN
Although the quiescent center (QC) is crucial to root development, the molecular mechanisms that regulate its postembryonic maintenance remain obscure. In this study, a semi-dominant mutant that exhibits pleiotropic defects in root tissues, which includes the root cap, lateral and crown roots, was isolated. The mutant is characterized by a loss of QC identity during postembryonic development, and the displayed defects result from a stabilizing mutation in domain II of OsIAA23 (Os06g39590). Expression of OsIAA23 is specific to the QC of the root tip during the development of primary, lateral and crown roots. Consistent with OsIAA23 expression in the QC, the auxin signaling marked by DR5p::GUS (ß-glucuronidase) was absent in the QC region of Osiaa23. Transgenic rice plants harboring Osiaa23 under the control of the QHB promoter mimic partially the defects of Osiaa23. These results indicate that the maintenance of the QC is dependent on OsIAA23-mediated auxin signaling in the QC. These findings provide insight into Aux/IAA-based auxin signaling during postembryonic maintenance of the QC in plants.
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Ácidos Indolacéticos/metabolismo , Meristema/metabolismo , Oryza/genética , Proteínas de Plantas/metabolismo , Transducción de Señal , Secuencia de Aminoácidos , Clonación Molecular , Regulación de la Expresión Génica de las Plantas , Meristema/genética , Datos de Secuencia Molecular , Mutación , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , ARN de Planta/genéticaRESUMEN
Root hair growth requires intensive cell-wall modification. This study demonstrates that root hair-specific expansin As, a sub-clade of the cell wall-loosening expansin proteins, are required for root hair elongation in rice (Oryza sativa L.). We identified a gene encoding EXPA17 (OsEXPA17) from a rice mutant with short root hairs. Promoter::reporter transgenic lines exhibited exclusive OsEXPA17 expression in root hair cells. The OsEXPA17 mutant protein (OsexpA17) contained a point mutation, causing a change in the amino acid sequence (Gly104âArg). This amino acid alteration is predicted to disrupt a highly conserved disulfide bond in the mutant. Suppression of OsEXPA17 by RNA interference further confirmed requirement for the gene in root hair elongation. Complementation of the OsEXPA17 mutant with other root hair EXPAs (OsEXPA30 and Arabidopsis EXPA7) can restore root hair elongation, indicating functional conservation of these root hair EXPAs in monocots and dicots. These results demonstrate that members of the root hair EXPA sub-clade play a crucial role in root hair cell elongation in Graminaceae.
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Oryza/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Aumento de la Célula , Clonación Molecular , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Prueba de Complementación Genética , Vectores Genéticos , Oryza/genética , Oryza/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Plantas Modificadas Genéticamente/metabolismo , Mutación Puntual , Estructura Terciaria de Proteína , Interferencia de ARNRESUMEN
BACKGROUND: Alcohol increases the expression of Group 1 metabotropic glutamate receptors (mGluRs) and their associated scaffolding protein Homer2 and stimulates phosphatidylinositol 3-kinase (PI3K) within the nucleus accumbens (NAC). Moreover, functional studies suggest that NAC Group 1 mGluR/Homer2/PI3K signaling may be a potential target for pharmacotherapeutic intervention in alcoholism. METHODS: Immunoblotting was conducted to examine the effects of alcohol consumption under drinking-in-the-dark (DID) procedures on Group 1 mGluR-associated proteins in C57BL/6J (B6) mice. Follow-up behavioral studies examined the importance of Group 1 mGluR/Homer2/PI3K signaling within the NAC shell for limited-access alcohol drinking. Finally, immunoblotting examined whether the NAC expression of Group 1 mGluR-associated proteins is a genetic correlate of high alcohol drinking using a selectively bred high DID (HDID-1) mouse line. RESULTS: Limited-access alcohol drinking under DID procedures up-regulated NAC shell Homer2 levels, concomitant with increases in mGluR5 and NR2B. Intra-NAC shell blockade of mGluR5, Homer2, or PI3K signaling, as well as transgenic disruption of the Homer binding site on mGluR5, decreased alcohol consumption in B6 mice. Moreover, transgenic disruption of the Homer binding site on mGluR5 and Homer2 deletion both prevented the attenuating effect of mGluR5 and PI3K blockade upon intake. Finally, the basal NAC shell protein expression of mGluR1 and Homer2 was increased in offspring of HDID-1 animals. CONCLUSIONS: Taken together, these data further implicate Group 1 mGluR signaling through Homer2 within the NAC in excessive alcohol consumption.
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Alcoholismo/genética , Alcoholismo/fisiopatología , Núcleo Accumbens/fisiología , Receptores de Ácido Kaínico/genética , Receptores de Ácido Kaínico/fisiología , Alcoholismo/psicología , Animales , Western Blotting , Proteínas Portadoras/genética , Depresores del Sistema Nervioso Central/sangre , Etanol/sangre , Proteínas de Andamiaje Homer , Masculino , Ratones , Ratones Noqueados , Fosfatidilinositol 3-Quinasas/fisiología , Receptores de N-Metil-D-Aspartato/genética , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
Four H7N3 avian influenza viruses (AIVs) were isolated from domestic ducks in live-poultry markets in Zhejiang Province, Eastern China, in 2011. All viruses were characterized by whole-genome sequencing with subsequent phylogenetic analysis and genetic comparison. Phylogenetic analysis of all eight viral genes showed that the viruses clustered in the Eurasian lineage of influenza viruses. The hemagglutinin cleavage site of all viruses indicated that the four strains were low-pathogenic avian influenza viruses.
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Patos/virología , Genoma Viral , Subtipo H7N3 del Virus de la Influenza A/genética , Subtipo H7N3 del Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/epidemiología , Filogenia , Análisis de Secuencia de ADN , Secuencia de Aminoácidos , Animales , China/epidemiología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H7N3 del Virus de la Influenza A/clasificación , Gripe Aviar/virología , Datos de Secuencia Molecular , Neuraminidasa/genética , Aves de Corral , Enfermedades de las Aves de Corral/epidemiología , Enfermedades de las Aves de Corral/virologíaRESUMEN
This study describes the characterization of seven H5N1 avian influenza viruses from domestic ducks in Eastern China in 2011. Phylogenetic analysis showed these viruses were closely related to an H5N1 virus circulating in wild birds in Hong Kong. Some characteristics of these viruses were similar to those of an H5N1 strain that circulated in China and Vietnam (2003-2004). The virulence of three isolates was examined in chickens and mice, and they were found to be highly pathogenic in chickens but showed low pathogenicity in mice. These results suggest that continued H5N1 surveillance in poultry should be used as an early warning system for avian influenza outbreaks.
Asunto(s)
Patos/virología , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Gripe Aviar/virología , Enfermedades de las Aves de Corral/virología , Animales , China , Femenino , Humanos , Subtipo H5N1 del Virus de la Influenza A/clasificación , Subtipo H5N1 del Virus de la Influenza A/genética , Gripe Aviar/epidemiología , Ratones , Ratones Endogámicos BALB C , Filogenia , Enfermedades de las Aves de Corral/epidemiologíaRESUMEN
BACKGROUND: Though case fatality rate (CFR) is widely used to reflect COVID-19 fatality risk, its use is limited by large temporal and spatial variation. Hospital mortality rate (HMR) is also used to assess the severity of COVID-19, but HMR data is not directly available globally. Alternative metrics are needed for COVID-19 severity and fatality assessment. METHODS: We introduce new metrics for COVID-19 fatality risk measurements/monitoring and a new mathematical model to estimate average hospital length of stay for deaths (Ldead) and discharges (Ldis). Multiple data sources were used for our analyses. FINDINGS: We propose three, new metrics: hospital occupancy mortality rate (HOMR), ratio of total deaths to hospital occupancy (TDHOR), and ratio of hospital occupancy to cases (HOCR), for dynamic assessment of COVID-19 fatality risk. Estimated Ldead and Ldis for 501,079 COVID-19 hospitalizations in 34 US states between 7 August 2020 and 1 March 2021 were 18·2(95%CI:17·9-18·5) and 14·0(95%CI:13·9-14·0) days, respectively. We found the dramatic changes in COVID-19 CFR observed in 27 countries during early stages of the pandemic were mostly caused by undiagnosed cases. Compared to the first week of November 2021, the week mean HOCRs (mimics hospitalization-to-case ratio) for Omicron variant (58·6% of US new cases as of 25 December 2021) decreased 65·16% in the US as of 16 January 2022. INTERPRETATION: The new and reliable measurements described here could be useful for COVID-19 fatality risk and variant-associated risk monitoring. FUNDING: No specific funding was associated with the present study.