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2.
mBio ; 9(3)2018 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-29789370

RESUMEN

The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in support of such a role of PhyK is missing. Here, we identify a single-domain response regulator, MrrA, that is essential for general stress response activation in C. crescentus We demonstrate that PhyK does not function as a kinase but accepts phosphoryl groups from MrrA and passes them on to PhyR, adopting the role of a histidine phosphotransferase. MrrA is phosphorylated by at least six histidine kinases that likely serve as stress sensors. MrrA also transfers phosphate to LovK, a histidine kinase involved in C. crescentus holdfast production and attachment, which also negatively regulates the general stress response. We show that LovK together with the response regulator LovR acts as a phosphate sink to redirect phosphate flux away from the PhyKR branch. In agreement with the biochemical data, an mrrA mutant is unable to activate the general stress response and shows a hyperattachment phenotype, which is linked to decreased expression of the major holdfast inhibitory protein HfiA. We propose that MrrA serves as a central phosphorylation hub that coordinates the general stress response with C. crescentus development and other adaptive behaviors. The characteristic bow-tie architecture of this phosphorylation network with MrrA as the central knot may expedite the evolvability and species-specific niche adaptation of this group of bacteria.IMPORTANCE Two-component systems (TCSs) consisting of a histidine kinase and a cognate response regulator are predominant signal transduction systems in bacteria. To avoid cross talk, TCSs are generally thought to be highly insulated from each other. However, this notion is based largely on studies of the HisKA subfamily of histidine kinases, while little information is available for the HWE and HisKA2 subfamilies. The latter have been implicated in the alphaproteobacterial general stress response. Here, we show that in the model organism Caulobacter crescentus an atypical FATGUY-type single-domain response regulator, MrrA, is highly promiscuous in accepting and transferring phosphoryl groups from and to multiple up- and downstream kinases, challenging the current view of strictly insulated TCSs. Instead, we propose that FATGUY response regulators have evolved in alphaproteobacteria as central phosphorylation hubs to broadly sample information and distribute phosphoryl groups between the general stress response pathway and other TCSs, thereby coordinating multiple cellular behaviors.


Asunto(s)
Proteínas Bacterianas/metabolismo , Caulobacter crescentus/fisiología , Proteínas Bacterianas/genética , Caulobacter crescentus/genética , Regulación Bacteriana de la Expresión Génica , Fosforilación , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Transducción de Señal , Estrés Fisiológico
3.
Nano Lett ; 15(11): 7567-73, 2015 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-26480237

RESUMEN

Two-dimensional transition metal dichalcogenide semiconductors are intriguing hosts for quantum light sources due to their unique optoelectronic properties. Here, we report that strain gradients, either unintentionally induced or generated by substrate patterning, result in spatially and spectrally isolated quantum emitters in mono- and bilayer WSe2. By correlating localized excitons with localized strain variations, we show that the quantum emitter emission energy can be red-tuned up to a remarkable ∼170 meV. We probe the fine-structure, magneto-optics, and second-order coherence of a strained emitter. These results raise the prospect of strain-engineering quantum emitter properties and deterministically creating arrays of quantum emitters in two-dimensional semiconductors.

4.
Exp Oncol ; 34(1): 53-6, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22453150

RESUMEN

BACKGROUND AND AIM: Endoglin is a proliferation-associated antigen on endothelial cells and essential for angiogenesis. Soluble endoglin (s­endoglin), formed by proteolytic cleavage of ectodomain of membrane receptor could be an indicator of tumor­activated endothelium. The aim of present study was to analyze changes of s­endoglin level in plasma of lung cancer patients following surgical resection and to estimate the correlation of s­endoglin with other soluble receptors, sTie2 and sVEGF R1. PATIENTS AND METHODS: The study group consisted of 37 patients with stage I of non-small cell lung cancer. Plasma concentrations of s­endoglin, sTie2 and sVEGF R1 were evaluated by ELISA, three times: before surgical resection and on postoperative day 7 and 30. RESULTS: The median of s­endoglin concentration decreased significantly on postoperative day 7 when compared with preoperative level and next increased on 30(th) day and it was comparable with that before surgery. s-Endoglin correlated with another soluble receptors, with sTie2 both before surgery (r=0.44) and on postoperative day 7 (r=0.52) and on 30(th) day (r=0.58), with sVEGF R1 - only on postoperative day 7 (r=0.75). CONCLUSION: The increased level of serum endoglin in lung cancer patients compared to controls and its changes after surgical treatment suggest potential application of soluble form of endoglin as potential tumor marker.


Asunto(s)
Antígenos CD/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/cirugía , Receptores de Superficie Celular/sangre , Endoglina , Humanos , Receptor TIE-2/sangre , Factores de Tiempo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre
5.
Eur J Gynaecol Oncol ; 30(6): 646-9, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20099495

RESUMEN

PURPOSE OF INVESTIGATION: Angiogenesis is important in the promotion and progression of malignancy. The formation of new blood vessels is coordinated by many factors, angiopoietins among others. Overexpression of angiopoietins has been observed in various tumors. The aim of the study was to evaluate plasma concentration of Ang-1, Ang-2 and Tie-2 in cervical cancer. METHODS: The study group consisted of 34 patients with cervical cancer and the control group of 20 healthy volunteers. Plasma concentrations of Ang-1, Ang-2 and Tie-2 were evaluated by ELISA. RESULTS: Plasma concentrations of Ang-1, Ang-2, Tie-2 and Ang-1/Ang-2 ratios were significantly higher in cervical cancer patients than in controls. Although there was no correlation between concentration of Ang-1, Ang-2, Tie-2 and clinical stage (FIGO), the Ang-1/Ang-2 ratio was higher in Stage I than in II-III. Ang-1 correlated positively with Ang-2 and Tie-2 in a subgroup with Stage II-III and Ang-2 with Tie-2 in a subgroup with Stage I. CONCLUSION: Plasma concentrations of Ang- 1, Ang-2 and Tie-2 may be useful additional tumor markers in cervical cancer.


Asunto(s)
Angiopoyetina 1/sangre , Angiopoyetina 2/sangre , Receptor TIE-2/sangre , Neoplasias del Cuello Uterino/sangre , Estudios de Casos y Controles , Femenino , Humanos , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/diagnóstico
6.
Cryo Letters ; 29(2): 145-56, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18516344

RESUMEN

The ultrastructure of cells within shoot tips of S. tuberosum 'Désirée' was studied after different steps of the DMSO droplet cryopreservation method. After 2 h of DMSO treatment, cells contained numerous small vesicles, while at the same time mitochondria and chloroplasts had increased in size and vacuoles had assumed an irregular shape. After rapid cooling in liquid nitrogen, subsequent rewarming, and 1 h incubation there were no apparent changes in the ultrastructural organization of the cells, suggesting that they might be still intact. However, two days after rewarming, the meristematic dome area and part of the epidermis showed signs of extensive damage. Rupture of plasmalemma, plasmolysis and destruction of cell organelles as well as strong heterochromatisation of nuclei were observed. Survival and regeneration of cells were found mainly in leaf primordial regions. Here cells were very active, containing many mitochondria and intact or regenerating chloroplasts. Alternating temperature preculture of donor plants before shoot tip isolation improved the cryopreservation results (plant regeneration 46.5 percent) as compared to constantly warm precultured shoot tips (plant regeneration 20.0 percent), which showed slightly stronger damage after rewarming from liquid nitrogen.


Asunto(s)
Criopreservación/métodos , Meristema/ultraestructura , Brotes de la Planta/ultraestructura , Solanum tuberosum/ultraestructura , Supervivencia Celular/fisiología , Crioprotectores , Dimetilsulfóxido , Heterocromatina/ultraestructura , Meristema/citología , Meristema/fisiología , Nitrógeno , Orgánulos/ultraestructura , Fotoperiodo , Brotes de la Planta/citología , Brotes de la Planta/fisiología , Solanum tuberosum/citología , Solanum tuberosum/fisiología , Temperatura
7.
Przegl Lek ; 58(4): 232-6, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11450342

RESUMEN

The aim of the study was to present the frequency of acute drug overdosing by dependent patients in the years 1997, 1998, 1999 and 2000, and to compare the numbers of poisoned addicts suffering withdrawal syndrome and seeking detoxification. The analysis includes data for all drug addicts treated at the Kraków Department of Clinical Toxicology in years 1997, 1998, 1999 and 2000 because of drug overdosing and resultant acute intoxication, because of withdrawal syndrome and also the opiate dependent patients qualified to methadone maintenance programme. The patients dependent on ethanol were excluded. A progressive increase in number of poisonings with psychoactive substances was noted in analysed years, respectively 231, 298, 331 and 442 patients. Drugs of abuse, were the most frequent cause of admission. Also incidence rate of poisoning expressed per 10,000 of Kraków inhabitants was highest for the cases admitted because of overdosing or craving for narcotics. Opiate derivatives produced at home from poppy straw or from juice of poppy head (so called "kompot" or "Polish heroin") were the most common cause of admission in all the analysed years: increase in number of acutely poisoned, and also increase in number of opiate dependent patients who suffered withdrawal syndrome and sought detoxification was noted in 2000 as compared to years 1998 and 1999. Opiate derivatives followed by amphetamine, as the single toxic agent or in mixed combinations, were still the most common drugs of abuse detected in body fluids. The men were dominant in all the analysed years, but the increase in number of depended women was observed through the years under analysis.


Asunto(s)
Drogas Ilícitas/envenenamiento , Trastornos Relacionados con Sustancias/epidemiología , Adhesivos/envenenamiento , Adolescente , Adulto , Distribución por Edad , Comorbilidad , Sobredosis de Droga , Femenino , Humanos , Incidencia , Masculino , Metadona/uso terapéutico , Persona de Mediana Edad , Narcóticos/envenenamiento , Aceptación de la Atención de Salud/estadística & datos numéricos , Polonia/epidemiología , Psicotrópicos/envenenamiento , Distribución por Sexo , Solventes/envenenamiento , Síndrome de Abstinencia a Sustancias/epidemiología
8.
J Med Chem ; 18(4): 371-6, 1975 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-1121003

RESUMEN

The phosphorylations of B12H11OH2-,B12H10(OH)2-2-, and B20H17OH4-with POCl3 and (C6H5O)2POCl were investigated and the following derivatives were isolated: B12H11OPO3H3-,B12H11OPO3H2-2-,B12H11OPO(OC6H5)-2-2 minus, B12H11OPO(OC6H5)OH2 minus, b12h10(op2o6h2)2-4 minus, B12H10(OPO3H2)2-2 minus, B12Br10(OPO3H)2-4 minus, B12H10[O-PO(OC6H5)2]2-2 minus, B20H18OP2O6H2-4 minus, B20H18OPO3H2-3 minus. The B-O-P bonds proved very resistant to hydrolysis and the phosphates were administered in the for of Na+ salts at pH 7.2 to rats bearing subcutaneous glioma. The boron concentrations in tumors and the tumor/blood concentration ratios were compared with those of parent hydroxy derivatives. Except when the POH function was blocked by phenyl groups the phosphorylation invariably resulted in a greatly enhanced uptake of the borane into tumors and improved the tumor/blood boron ratio. The phopshate function appears to be one of the most effective handles for the incorporation of boron into brain tumors and the compounds show considerable promise for use in the neutron capture therapy of brain tumors.


Asunto(s)
Boranos/síntesis química , Organofosfatos/síntesis química , Compuestos Organofosforados/síntesis química , Animales , Boranos/sangre , Boranos/metabolismo , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Ependimoma/metabolismo , Glioma/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Ratones Endogámicos C3H , Neoplasias Experimentales , Organofosfatos/sangre , Organofosfatos/metabolismo , Conejos , Ratas , Espectrofotometría Infrarroja
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