The tyrosyl-tRNA synthetase like gene located in the tyramine biosynthesis cluster of Enterococcus durans is transcriptionally regulated by tyrosine concentration and extracellular pH

<p>Abstract</p> <p>Background</p> <p>The tyramine producer <it>Enterococcus durans </it>IPLA655 contains all the necessary genes for tyramine biosynthesis, grouped in the TDC cluster. This cluster includes <it>tyrS</it>, an aminoacyl-tRNA synthetase like gene.</p> <p>Results</p> <p>This work shows that <it>tyrS </it>was maximally transcribed in absence of tyrosine at acidic pH, showing a greater than 10-fold induction in mRNA levels over levels occurring in presence of tyrosine. Mapping of the <it>tyrS </it>transcriptional start site revealed an unusually long untranslated leader region of 322 bp, which displays the typical features of the T box transcriptional attenuation mechanism. The tyrosine concentration regulation of <it>tyrS </it>was found to be mediated by a transcription antitermination system, whereas the specific induction at acidic pH was regulated at transcription initiation level.</p> <p>Conclusions</p> <p>The expression of the <it>tyrS </it>gene present in the TDC cluster of <it>E. durans </it>is transcriptionally regulated by tyrosine concentration and extracelular pH. The regulation is mediated by both an antitermination system and the promoter itself.</p

Treatment of Retinopathy of Prematurity with topical ketorolac tromethamine: a preliminary study

BACKGROUND: Retinopathy of Prematurity (ROP) is a common retinal neovascular disorder of premature infants. It is of variable severity, usually heals with mild or no sequelae, but may progress to blindness from retinal detachments or severe retinal scar formation. This is a preliminary report of the effectiveness and safety of a new and original use of topical ketorolac in preterm newborn to prevent the progression of ROP to the more severe forms of this disease. METHODS: From January 2001 to December 2002, all fifty nine preterm newborns with birthweight less than 1250 grams or gestational age less than 30 weeks of gestational age admitted to neonatal intensive care were eligible for treatment with topical ketorolac (0.25 milligrams every 8 hours in each eye). The historical comparison group included all 53 preterm newborns, with the same inclusion criteria, admitted between January 1999 and December 2000. RESULTS: Groups were comparable in terms of weight distribution, Apgar score at 5 minutes, incidence of sepsis, intraventricular hemorrhage and necrotizing enterocolitis. The duration of oxygen therapy was significantly longer in the control group. In the ketorolac group, among 43 children that were alive at discharge, one (2.3%) developed threshold ROP and cryotherapy was necessary. In the comparison group 35 children survived, and six child (17%) needed cryotherapy (Relative Risk 0.14, 95%CI 0.00 to 0.80, p = 0.041). Adjusting by duration of oxygen therapy did not significantly change these results. Adverse effects attributable to ketorolac were not detected. CONCLUSIONS: This preliminary report suggests that ketorolac in the form of an ophthalmic solution can reduce the risk of developing severe ROP in very preterm newborns, without producing significant adverse side effects. These results, although promising, should be interpreted with caution because of the weakness of the study design. This is an inexpensive and simple intervention that might ameliorate the progression of a disease with devastating consequences for children and their families. We believe that next logical step would be to assess the effectiveness of this intervention in a randomized controlled trial of adequate sample size

Bloom-forming cyanobacteria and dinoflagellates in five Argentinian reservoirs: Multi-year sampling

Harmful algal blooms are important threats to reservoir condition. Over a 15-year period, we sampled fiveArgentinian reservoirs to identify the responsible species for harmful algal blooms and determine the waterquality factors driving their occurrence. These reservoirs exhibit diverse morphological and hydrological characteristics and are distributed across varying climatic zones. Cyanobacterial blooms included an array of species,including toxin producers such as Raphidiopsis raciborskii, Aphanizomenon gracile, and Microcystis aeruginosa. Incontrast, dinoflagellate blooms were predominantly characterized by Ceratium. The cyanobacterial blooms primarily occurred in the shallower reservoirs located in warmer regions, whereas dinoflagellate blooms occurredwhere temperatures were lower. The most intense blooms occurred during the summer, and although cyanobacterial and chlorophyte blooms co-occurred, they never coexisted with dinoflagellate blooms. We identifiedcyanotoxins in the reservoirs over the past three years, a phenomenon previously unreported in the region. Giventhat these reservoirs are drinking water sources for human populations, ongoing and systematic monitoring isneeded to protect public health. Controlling the proliferation of algae and cyanobacteria in reservoirs requiresresource management at the watershed level, and in the case of the Itiyuro and El Limon, requires binational management with Bolivia.Fil: Alvarez Dalinger, Florencia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Salta; ArgentinaFil: Borja, Claudia Nidia. Universidad Nacional de Salta. Facultad de Cs.naturales. Catedra Biologia y Diversidad de Protistas Autotrofos y Fungi.; ArgentinaFil: Lozano, Verónica Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Salta; ArgentinaFil: Moraña, Liliana Beatriz. Universidad Nacional de Salta. Facultad de Cs.naturales. Catedra Biologia y Diversidad de Protistas Autotrofos y Fungi.; ArgentinaFil: Salusso, Maria Monica. Universidad Nacional de Salta. Facultad de Cs.naturales. Catedra Biologia y Diversidad de Protistas Autotrofos y Fungi.; Argentin

Angiotensin II type 1 receptor is involved in hypertension and vascular alterations caused by environmental toxicant hexachlorobenzene

Environmental hexachlorobenzene (HCB) increases blood pressure (BP) in female rats, causing alterations in arterial structure and function. Here we study the role of Angiotensin II receptor type 1 (AT1) in HCB-induced hypertension through the use of AT1 antagonist losartan. HCB-treated male rats showed a 22.7% increase in BP which was prevented by losartan. Losartan blocked HCB-induced changes in arterial morphology (decreased aorta cell number and increased wall thickness). Losartan also prevented HCB-induced alterations in artery relaxation by acetylcholine and nitroprusside but not the reduction in the maximum contraction by phenylephrine. Losartan rescued arterial molecular alterations caused by HCB (i.e. an increase in TGF-β1 and AT1 expression and a decrease in eNOS expression and nitrite levels) and reduced hydrogen sulfide plasma concentration. In conclusion: in this work we demonstrate that AT1 activity is involved in HCB effects on the vascular system leading to hypertension.Fil: Romero Caimi, Vanesa Giselle. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Gorzalczany, Susana Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; ArgentinaFil: Bonazzola, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional; ArgentinaFil: Deza, Zahira Agustina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Roson, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional; ArgentinaFil: Alvarez, Laura. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Castilla Lozano, Maria del Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional; Argentin

Secreted phospholipase A2-IIA modulates transdifferentiation of cardiac fibroblast through EGFR transactivation: An inflammation–fibrosis link

Producción CientíficaSecreted phospholipase A2-IIA (sPLA2-IIA) is a pro-inflammatory protein associated with cardiovascular disorders, whose functions and underlying mechanisms in cardiac remodelling are still under investigation. We herein study the role of sPLA2-IIA in cardiac fibroblast (CFs)-to-myofibroblast differentiation and fibrosis, two major features involved in cardiac remodelling, and also explore potential mechanisms involved. In a mice model of dilated cardiomyopathy (DCM) after autoimmune myocarditis, serum and cardiac sPLA2-IIA protein expression were found to be increased, together with elevated cardiac levels of the cross-linking enzyme lysyl oxidase (LOX) and reactive oxygen species (ROS) accumulation. Exogenous sPLA2-IIA treatment induced proliferation and differentiation of adult rat CFs. Molecular studies demonstrated that sPLA2-IIA promoted Src phosphorylation, shedding of the membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) ectodomain and EGFR phosphorylation, which triggered phosphorylation of ERK, P70S6K and rS6. This was also accompanied by an up-regulated expression of the bone morphogenic protein (BMP)-1, LOX and collagen I. ROS accumulation were also found to be increased in sPLA2-IIA-treated CFs. The presence of inhibitors of the Src/ADAMs-dependent HB-EGF shedding/EGFR pathway abolished the CF phenotype induced by sPLA2-IIA. In conclusion, sPLA2-IIA may promote myofibroblast differentiation through its ability to modulate EGFR transactivation and signalling as key mechanisms that underlie its biological and pro-fibrotic effects.Ministerio de Economía, Industria y Competitividad (grants SAF2012-34460 and SAF2016-81063)Instituto de Salud Carlos III (grant PI18/010257729

Application of IPSET-thrombosis in 1366 Patients Prospectively Followed From the Spanish Registry of Essential Thrombocythemia

Thrombosis; Essential thrombocythemiaTrombosi; Trombocitèmia essencialTrombosis; Trombocitemia esencialThe International Prognostic Score of thrombosis in Essential Thrombocythemia (IPSET-thrombosis) and its revised version have been proposed to guide thrombosis prevention strategies. We evaluated both classifications to prognosticate thrombosis in 1366 contemporary essential thrombocythemia (ET) patients prospectively followed from the Spanish Registry of ET. The cumulative incidence of thrombosis at 10 years, taking death as a competing risk, was 11.4%. The risk of thrombosis was significantly higher in the high-risk IPSET-thrombosis and high-risk revised IPSET-thrombosis, but no differences were observed among the lower risk categories. Patients allocated in high-risk IPSET-thrombosis (subdistribution hazard ratios [SHR], 3.7 [95% confidence interval, CI, 1.6-8.7]) and high-risk revised IPSET-thrombosis (SHR, 3.2 [95% CI, 1.4-7.45]) showed an increased risk of arterial thrombosis, whereas both scoring systems failed to predict venous thrombosis. The incidence rate of thrombosis in intermediate risk revised IPSET-thrombosis (aged >60 years, JAK2-negative, and no history of thrombosis) was very low regardless of the treatment administered (0.9% and 0% per year with and without cytoreduction, respectively). Dynamic application of the revised IPSET-thrombosis showed a low rate of thrombosis when patients without history of prior thrombosis switched to a higher risk category after reaching 60 years of age. In conclusion, IPSET-thrombosis scores are useful for identifying patients at high risk of arterial thrombosis, whereas they fail to predict venous thrombosis. Controlled studies are needed to determine the appropriate treatment of ET patients assigned to the non-high-risk categories.The Spanish registry of Essential thrombocythemia is financed with GEMFIN’s own funds without direct collaboration from any pharmaceutical company. This work was supported by PI21/00231, PI21/00347, and PI21/00538 from the Instituto de Salud Carlos III (ISCIII), through the Plan Estatal de Investigación Científica y Técnica y de Innovación

Cyanobacteria in a subtropical reservoir of the province of Salta (Argentina)

El embalse Limón se ha convertido en la principal fuente de agua potable para el 80% de lapoblación del norte de la provincia de Salta (22° 05?47,90??S-63° 44? 19,48?? W). Al presente, no existeinformación sistematizada de las algas del fitoplancton presentes en esta presa. Se analizaron 19muestras del período 2013-2015 en ambas fases del ciclo hidrológico, según técnicas estandarizadas,con el objeto de evaluar la representatividad de cianobacterias potencialmente tóxicas en Limón y suimportancia relativa en el fitoplancton. Existió un predominio de cianobacterias, con un incrementointeranual significativo, siendo éstas más abundantes en los estiajes, con un promedio de 110.160células en 2015, con predominio de Cylindrospermopsis raciborskii y Raphidiopsis mediterranea (75.027y 170.000 células/ml). Entre las especies con potencial toxicogénico se destacaron por sus densidadesAnabaenopsis elenkinii, Aphanizomenon gracile, Aphanocapsa annulata, Coelomoron tropicale,Chroococcus dispersus, C. raciborskii, Microcysis flos-aquae, Planktolyngbya limnetica, Pseudanabaenalimnetica, R. mediterranea y R. curvata. La representatividad del grupo dentro del fitoplancton fuesuperior al 70 %. Se concluye que el cuerpo de agua es un ambiente de riesgo y debe ser monitoreadopermanentemente para su empleo para agua de consumo humano.Cyanobacteria in a subtropical reservoir of the province of Salta (Argentina). The Limón reservoir has become the main source of drinking water for 80% of the population of the north of the province of Salta (22° 05' 47.90'' S - 63° 44' 19.48'' W). At present, there is no systematized information on phytoplankton algae present in this dam. We analyzed 19 samples from the period 2013-2015, in both phases of the hydrological cycle, according to standardized techniques, in order to evaluate the representativeness of potentially toxic Cyanobacteria in Limón and their relative importance in phytoplankton. There was a predominance of Cyanobacteria, with a significant interannual increase, these being more abundant during dry season, with an average of 110,160 cells/ml in 2015, with a predominance of Cylindrospermopsis raciborskii and Raphidiopsis mediterranea (75,027 and 170,000 cells/ml repectively). Among the species with toxic potential, Anabaenopsis elenkinii, Aphanizomenon gracile, Aphanocapsa annulata, Coelomoron tropicale, Chroococcus dispersus, C. raciborskii, Microcysis flos-aquae, Planktolyngbya limnetica, Pseudanabaena limnetica,R. mediterranea and R. curvata were notable for their densities. The representativeness of this group within the phytoplankton was greater than 70%. It is concluded that the body of water is an environment of risk and must be monitored permanently for its use for water for human consumption.Fil: Vidaurre, Andrea. Universidad Nacional de Salta; ArgentinaFil: Alvarez Dalinger, Florencia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Moraña, Liliana Beatriz. Universidad Nacional de Salta; ArgentinaFil: Salusso, Maria Monica. Universidad Nacional de Salta; Argentin