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BACKGROUND: Rhizobacteria play an important role in plant defense and could be promising sources of biocontrol agents. This study aimed to screen antagonistic bacteria and develop a biocontrol system for root rot complex of Panax notoginseng. METHODS: Pure-culture methods were used to isolate bacteria from the rhizosphere soil of notoginseng plants. The identification of isolates was based on the analysis of 16S ribosomal RNA (rRNA) sequences. RESULTS: A total of 279 bacteria were obtained from rhizosphere soils of healthy and root-rot notoginseng plants, and uncultivated soil. Among all the isolates, 88 showed antagonistic activity to at least one of three phytopathogenic fungi, Fusarium oxysporum, Fusarium solani, and Phoma herbarum mainly causing root rot disease of P. notoginseng. Based on the 16S rRNA sequencing, the antagonistic bacteria were characterized into four clusters, Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetesi. The genus Bacillus was the most frequently isolated, and Bacillus siamensis (Hs02), Bacillus atrophaeus (Hs09) showed strong antagonistic activity to the three pathogens. The distribution pattern differed in soil types, genera Achromobacter, Acidovorax, Brevibacterium, Brevundimonas, Flavimonas, and Streptomyces were only found in rhizosphere of healthy plants, while Delftia, Leclercia, Brevibacillus, Microbacterium, Pantoea, Rhizobium, and Stenotrophomonas only exist in soil of diseased plant, and Acinetobacter only exist in uncultivated soil. CONCLUSION: The results suggest that diverse bacteria exist in the P. notoginseng rhizosphere soil, with differences in community in the same field, and antagonistic isolates may be good potential biological control agent for the notoginseng root-rot diseases caused by F. oxysporum, Fusarium solani, and Panax herbarum.
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4-Aminopyridine (4-AP, fampridine) is used clinically to improve neuromuscular function in patients with multiple sclerosis, spinal cord injury, and myasthenia gravis. 4-AP can increase neuromuscular and synaptic transmission by directly stimulating high voltage-activated (HVA) Ca(2+) channels independent of its blocking effect on voltage-activated K(+) channels. Here we provide new evidence that the potentiating effect of 4-AP on HVA Ca(2+) channels depends on the specific combination of voltage-activated calcium channel α1 (Cavα1) and voltage-activated calcium channel ß (Cavß) subunits. Among the four Cavß subunits examined, Cavß3 was the most significant subunit involved in the 4-AP-induced potentiation of both L-type and N-type currents. Of particular note, 4-AP at micromolar concentrations selectively potentiated L-type currents reconstituted with Cav1.2, α2δ1, and Cavß3. In contrast, 4-AP potentiated N-type currents only at much higher concentrations and had little effect on P/Q-type currents. In a phrenic nerve-diaphragm preparation, blocking L-type Ca(2+) channels eliminated the potentiating effect of low concentrations of 4-AP on end-plate potentials. Furthermore, 4-AP enhanced the physical interaction of Cav1.2 and Cav2.2 subunits to Cavß3 and also increased their trafficking to the plasma membrane. Site-directed mutagenesis identified specific regions in the guanylate kinase, HOOK, and C-terminus domains of the Cavß3 subunit crucial to the ability of 4-AP to potentiate L-type and N-type currents. Our findings indicate that 4-AP potentiates HVA Ca(2+) channels by enhancing reciprocal Cav1.2-Cavß3 and Cav2.2-Cavß3 interactions. The therapeutic effect of 4-AP on neuromuscular function is probably mediated by its actions on Cavß3-containing L-type Ca(2+) channels.
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4-Aminopiridina/farmacología , Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo N/efectos de los fármacos , Secuencia de Aminoácidos , Canales de Calcio Tipo L/química , Canales de Calcio Tipo N/química , Células HEK293 , Humanos , Datos de Secuencia Molecular , Unión Neuromuscular/fisiología , Subunidades de Proteína , Transmisión Sináptica/efectos de los fármacosRESUMEN
Hematopoietic growth factors (HGF) are recommended therapy for high dose radiation exposure, but unfavorable administration schedules requiring early and repeat dosing limit the logistical ease with which they can be used. In this report, using a previously described murine model of H-ARS, survival efficacy and effect on hematopoietic recovery of unique PEGylated HGF were investigated. The PEGylated-HGFs possess longer half-lives and more potent hematopoietic properties than corresponding non-PEGylated-HGFs. C57BL/6 mice underwent single dose lethal irradiation (7.76-8.72 Gy, Cs, 0.62-1.02 Gy min) and were treated with various dosing regimens of 0.1, 0.3, and 1.0 mg kg of analogs of human PEG-G-CSF, murine PEG-GM-CSF, or human PEG-IL-11. Mice were administered one of the HGF analogs at 24-28 h post irradiation, and in some studies, additional doses given every other day (beginning with the 24-28 h dose) for a total of three or nine doses. Thirty-day (30 d) survival was significantly increased with only one dose of 0.3 mg kg of PEG-G-CSF and PEG-IL-11 or three doses of 0.3 mg kg of PEG-GM-CSF (p ≤ 0.006). Enhanced survival correlated with consistently and significantly enhanced WBC, NE, RBC, and PLT recovery for PEG-G- and PEG-GM-CSF, and enhanced RBC and PLT recovery for PEG-IL-11 (p ≤ 0.05). Longer administration schedules or higher doses did not provide a significant additional survival benefit over the shorter, lower dose, schedules. These data demonstrate the efficacy of BBT's PEG-HGF to provide significantly increased survival with fewer injections and lower drug doses, which may have significant economic and logistical value in the aftermath of a radiation event.
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Síndrome de Radiación Aguda/tratamiento farmacológico , Modelos Animales de Enfermedad , Factor Estimulante de Colonias de Granulocitos/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Hematopoyesis/efectos de los fármacos , Interleucina-11/farmacología , Polietilenglicoles/química , Síndrome de Radiación Aguda/fisiopatología , Animales , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/química , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/química , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Hematopoyesis/efectos de la radiación , Humanos , Interleucina-11/administración & dosificación , Interleucina-11/química , Interleucina-11/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacología , Polietilenglicoles/uso terapéutico , Análisis de Supervivencia , Adulto JovenRESUMEN
AIMS: Although illicit drug purity is a widely discussed health risk, research explaining its geographic variation within a country is rare. This study examines whether proximity to the US-Mexico border, the United States' primary drug import portal, is associated with geographic variation in US methamphetamine, heroin and cocaine purity. DESIGN: Distances (proximity) between the US-Mexico border and locations of methamphetamine, cocaine and heroin seizures/acquisitions (n = 239,070) recorded in STRIDE (System to Retrieve Information from Drug Evidence) were calculated for the period of 1990-2004. The association of drug purity with these distances and other variables, including time and seizure/acquisition size, was examined using hierarchical multivariate linear modeling (HMLM). SETTING: Coterminous United States. FINDINGS: Methamphetamine, cocaine and heroin purity generally decreased with distance from the US-Mexico border. Heroin purity, however, after initially declining with distance, turned upwards-a U-shaped association. During 2000-04, methamphetamine purity also had a U-shaped association with distance. For each of the three drugs, temporal changes in the purity of small acquisitions (<10 g) were typically more dynamic in areas closer to the US-Mexico border. CONCLUSIONS: Geographic variance in methamphetamine, cocaine and heroin purity throughout the coterminous United States was associated with US-Mexico border proximity. The U-shaped associations between border-distance and purity for heroin and methamphetamine may be due to imports of those drugs via the eastern United States and southeast Canada, respectively. That said, areas closer to the US-Mexico border generally had relatively high illicit drug purity, as well as more dynamic change in the purity of small ('retail level') drug amounts.